PMID- 11191501 TI - Consent for HIV counselling and testing. PMID- 11191502 TI - Consent for trials in palliative care. PMID- 11191503 TI - Operation Smile: plastic surgery with few resources. PMID- 11191504 TI - Facial surgery: body and soul. PMID- 11191505 TI - The mentally ill in prison: developments in Latvia. PMID- 11191506 TI - Mental or criminal? PMID- 11191507 TI - Public health in eastern Europe. PMID- 11191508 TI - Striving for global drug availability. PMID- 11191509 TI - Public-health priorities in the industrialised world. PMID- 11191510 TI - Role of education in the use of contraception. PMID- 11191511 TI - In-vitro fertilisation: a future with no limits? PMID- 11191512 TI - Research resurgence in Uruguay. PMID- 11191513 TI - Academic medicine sets focus on clinical research. PMID- 11191514 TI - Respiratory diseases in Africa: causes and effects. PMID- 11191515 TI - Burden of chronic obstructive pulmonary disease. PMID- 11191516 TI - Female genital mutilation: what can be done? PMID- 11191517 TI - The changing perceptions of sex and sexuality. PMID- 11191518 TI - More than just eczema. PMID- 11191519 TI - Availability of pharmaceutical drugs. PMID- 11191520 TI - Aesthetic surgery: coming of age. PMID- 11191521 TI - Molecular answers to tuberculous questions. PMID- 11191522 TI - Multiple-drug-resistant tuberculosis. PMID- 11191523 TI - Tropical diseases and the 10/90 gap. PMID- 11191524 TI - Response to haemorrhagic fevers in Europe. PMID- 11191525 TI - Women's health and human rights needs. PMID- 11191526 TI - The two faces of health care for women. PMID- 11191527 TI - A leukaemia treatment programme in El Salvador. PMID- 11191528 TI - Gene therapy in haematology and oncology. PMID- 11191529 TI - Let's not make the same mistakes. PMID- 11191530 TI - What's in a name? PMID- 11191531 TI - Renal-dose dopamine: will the message now get through? PMID- 11191532 TI - Rekindling old controversy on elusive lair of latent tuberculosis. PMID- 11191533 TI - Targeting cytokines in asthma therapy: round one. PMID- 11191534 TI - Exercise testing in rapid-access clinics for assessment of chest pain. PMID- 11191535 TI - Serological diagnosis of inflammatory bowel disease. PMID- 11191536 TI - Workplace bullying: icebergs in sight, soundings needed. PMID- 11191537 TI - Effect of sibutramine on weight maintenance after weight loss: a randomised trial. STORM Study Group. Sibutramine Trial of Obesity Reduction and Maintenance. AB - BACKGROUND: Sibutramine is a tertiary amine that has been shown to induce dose dependent weight loss and to enhance the effects of a low-calorie diet for up to a year. We did a randomised, double-blind trial to assess the usefulness of sibutramine in maintaining substantial weight loss over 2 years. METHODS: Eight European centres recruited 605 obese patients (body-mass index 30-45 kg/m2) for a 6-month period of weight loss with sibutramine (10 mg/day) and an individualised 600 kcal/day deficit programme based on measured resting metabolic rates. 467 (77%) patients with more than 5% weight loss were then randomly assigned 10 mg/day sibutramine (n=352) or placebo (n=115) for a further 18 months. Sibutramine was increased up to 20 mg/day if weight regain occurred. The primary outcome measure was the number of patients at year 2 maintaining at least 80% of the weight lost between baseline and month 6. Secondary outcomes included changes in uric acid concentrations and glycaemic and lipid variables. Analysis was by intention to treat. FINDINGS: 148 (42%) individuals in the sibutramine group and 58 (50%) in the placebo group dropped out. Of the 204 sibutramine-treated individuals who completed the trial, 89 (43%) maintained 80% or more of their original weight loss, compared with nine (16%) of the 57 individuals in the placebo group (odds ratio 4.64, p<0.001). Patients had substantial decreases over the first 6 months with respect to triglycerides, VLDL cholesterol, insulin, C peptide, and uric acid; these changes were sustained in the sibutramine group but not the placebo group. HDL cholesterol concentrations rose substantially in the second year: overall increases were 20.7% (sibutramine) and 11.7% (placebo, p<0.001). 20 (3%) patients were withdrawn because of increases in blood pressure; in the sibutramine group, systolic blood pressure rose from baseline to 2 years by 0.1 mm Hg (SD 12.9), diastolic blood pressure by 2.3 mm Hg (9.4), and pulse rate by 4.1 beats/min (11.9). INTERPRETATION: This individualised management programme achieved weight loss in 77% of obese patients and sustained weight loss in most patients continuing therapy for 2 years. Changes in concentrations of HDL cholesterol, VLDL cholesterol, and triglyceride, but not LDL cholesterol, exceed those expected either from weight loss alone or when induced by other selective therapies for low concentrations of HDL cholesterol relating to coronary heart disease. PMID- 11191538 TI - Non-invasive pressure support ventilation versus conventional oxygen therapy in acute cardiogenic pulmonary oedema: a randomised trial. AB - BACKGROUND: Non-invasive pressure support ventilation (NIPSV) is an effective treatment for acute respiratory failure in patients with chronic obstructive pulmonary disease. We assessed the efficacy of this therapy in acute cardiogenic pulmonary oedema in a randomised comparison with conventional oxygen therapy. METHODS: 40 patients were randomly assigned conventional oxygen therapy or NIPSV supplied by a standard ventilator through a face mask, with adjustment of tidal volume and pressure support in addition to a positive end-expiratory pressure of 5 cm water. Physiological measurements were obtained in the first 2 h and at 3 h, 4 h, and 10 h. The main endpoints were intubation rate and resolution time. Analyses were by intention to treat. FINDINGS: Three patients were withdrawn on the basis of clinical and chest radiography results. Endotracheal intubation was required in one (5%) of 19 patients assigned NIPSV and in six (33%) of 18 assigned conventional oxygen therapy (p=0.037). Resolution time (defined as a clinical improvement with oxygen saturation of 96% or more and respiratory rate less than 30 breaths/min) was significantly shorter in the NIPSV group (median 30 [IQR 15-53] vs 105 [50-230] min, p=0.002). NIPSV led to a rapid improvement in oxygenation in the first 2 h. There were no differences in hospital length of stay or mortality. INTERPRETATION: In this study of acute cardiogenic pulmonary oedema, NIPSV was superior to conventional oxygen therapy. Further studies should compare NIPSV with continuous positive airway pressure. PMID- 11191539 TI - Persistence of DNA from Mycobacterium tuberculosis in superficially normal lung tissue during latent infection. AB - BACKGROUND: A third of the world's population has latent infection with Mycobacterium tuberculosis, and in areas of low endemicity, most cases of active tuberculosis arise as a result of reactivation of latent bacilli. We sought to establish the cellular location of these latent organisms to facilitate their elimination. METHODS: We applied in-situ PCR to sections of macroscopically normal lung tissue from 13 individuals from Ethiopia and 34 from Mexico who had died from causes other than tuberculosis. Sections of lung tissue from six Norwegian individuals (ie, individuals from a non-endemic population) acted as negative controls, and six Ethiopian tuberculosis cases acted as positive controls. FINDINGS: Control necropsy samples from the Norwegian individuals were all negative by in-situ PCR and conventional PCR, whereas all samples from known Ethiopian tuberculosis cases were positive by both methods. However, in macroscopically normal lung tissue from Ethiopian and Mexican individuals without tuberculous lesions, the in-situ PCR revealed five of 13 and ten of 34 positive individuals, respectively. These results were confirmed by conventional PCR with extracted DNA. Positive cells included alveolar and interstitial macrophages, type II pneumocytes, endothelial cells, and fibroblasts. INTERPRETATION: M. tuberculosis can persist intracellularly in lung tissue without histological evidence of tuberculous lesions. M. tuberculosis DNA is situated not only in macrophages but also in other non-professional phagocytic cells. These findings contradict the dominant view that latent organisms exist in old classic tuberculous lesions, and have important implications for strategies aimed at the elimination of latent and persistent bacilli. PMID- 11191540 TI - Clinical picture: ipsilateral atherosclerotic and fibromuscular renal artery stenosis. PMID- 11191541 TI - Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial. Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group. AB - BACKGROUND: Low-dose dopamine is commonly administered to critically ill patients in the belief that it reduces the risk of renal failure by increasing renal blood flow. However, these effects have not been established in a large randomised controlled trial, and use of dopamine remains controversial. We have done a multicentre, randomised, double-blind, placebo-controlled study of low-dose dopamine in patients with at least two criteria for the systemic inflammatory response syndrome and clinical evidence of early renal dysfunction (oliguria or increase in serum creatinine concentration). METHODS: 328 patients admitted to 23 participating intensive-care units (ICUs) were randomly assigned a continuous intravenous infusion of low-dose dopamine (2 microg kg(-1) min(-1)) or placebo administered through a central venous catheter while in the ICU. The primary endpoint was the peak serum creatinine concentration during the infusion. Analyses excluded four patients with major protocol violations. FINDINGS: The groups assigned dopamine (n=161) and placebo (n=163) were similar in terms of baseline characteristics, renal function, and duration of trial infusion. There was no difference between the dopamine and placebo groups in peak serum creatinine concentration during treatment (245 [SD 144] vs 249 [147] micromol/L; p=0.93), in the increase from baseline to highest value during treatment (62 [107] vs 66 [108] micromol/L; p=0.82), or in the numbers of patients whose serum creatinine concentration exceeded 300 micromol/L (56 vs 56; p=0.92) or who required renal replacement therapy (35 vs 40; p=0.55). Durations of ICU stay (13 [14] vs 14 [15] days; p=0.67) and of hospital stay (29 [27] vs 33 [39] days; p=0.29) were also similar. There were 69 deaths in the dopamine group and 66 in the placebo group. INTERPRETATION: Administration of low-dose dopamine by continuous intravenous infusion to critically ill patients at risk of renal failure does not confer clinically significant protection from renal dysfunction. PMID- 11191542 TI - Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. AB - BACKGROUND: Interleukin-5 (IL-5) is essential for the formation of eosinophils, which are thought to have a major role in the pathogenesis of asthma and other allergic diseases. We aimed to assess the effects of monoclonal antibody to IL-5 on blood and sputum eosinophils, airway hyper-responsiveness, and the late asthmatic reaction to inhaled allergen in patients with mild asthma. METHODS: We did a double-blind randomised placebo-controlled trial, in which a single intravenous infusion of humanised (IgG-K) monoclonal antibody to IL-5 (SB-240563) was given at doses of 2.5 mg/kg (n=8) or 10.0 mg/kg (n=8). The effects of treatment on responses to inhaled allergen challenge, sputum eosinophils, and airway hyper-responsiveness to histamine were measured at weeks 1 and 4 with monitoring of blood eosinophil counts for up to 16 weeks. FINDINGS: Monoclonal antibody against IL-5 lowered the mean blood eosinophil count at day 29 from 0.25x10(9)/L (95% CI 0.16-0.34) in the placebo group to 0.04x10(9)/L (0.00-0.07) in the 10 mg/kg group (p<0.0001), and prevented the blood eosinophilia that follows allergen challenge. After inhaled allergen challenge, 9 days after treatment, the percentage sputum eosinophils were 12.2% in the placebo group and lowered to 0.9% (-1.2 to 3.0; p=0.0076) in the 10 mg/kg group, and this effect persisted at day 30 after the dose. There was no significant effect of monoclonal antibody to IL-5 on the late asthmatic response or on airway hyper-responsiveness to histamine. INTERPRETATION: A single dose of monoclonal antibody to IL-5 decreased blood eosinophils for up to 16 weeks and sputum eosinophils at 4 weeks, which has considerable therapeutic potential for asthma and allergy. However, our findings question the role of eosinophils in mediating the late asthmatic response and causing airway hyper-responsiveness. PMID- 11191543 TI - Effects of recombinant human interleukin-12 on eosinophils, airway hyper responsiveness, and the late asthmatic response. AB - BACKGROUND: Interleukin-12 (IL-12) is a macrophage-derived cytokine that modulates T lymphocyte responses and has the capacity to suppress allergic and eosinophilic inflammation. METHODS: We carried out a double-blind, randomised, parallel group clinical study, in which patients with mild allergic asthma were given subcutaneous recombinant human IL-12 at increasing weekly injections of 0.1, 0.25, 0.5 microg/kg (n=19), or placebo (n=20). We compared responses to inhaled allergen challenge 24 h before the first injection and 24 h after the final injection. Airways hyper-responsiveness and concentrations of peripheral blood eosinophils and sputum eosinophils were also assessed. FINDINGS: IL-12 caused a significant decrease from baseline in the main peripheral blood eosinophil count 24 h after the fourth injection compared with placebo (p=0.0001). Sputum eosinophils were also significantly decreased 24 h after allergen challenge when treated with IL-12 compared with placebo (p=0.024). IL-12 caused a non-significant trend towards improvement in airway hyper-responsiveness to histamine, but had no significant effect on the late asthmatic reaction after inhaled allergen challenge. After administration of IL-12, four of 19 patients withdrew prematurely; two with cardiac arrhythmias, one with abnormal liver function, and a single patient with severe flu-like symptoms. INTERPRETATION: We have shown that IL-12 lowers numbers of blood and sputum eosinophils, but without any significant effects on airway hyper-responsiveness or the late asthmatic reaction. This questions the role of eosinophils in mediating these reactions, and has important implications for development of new anti-inflammatory treatments. PMID- 11191544 TI - Familial Mediterranean Fever in a cold climate: read The Lancet. PMID- 11191545 TI - Chimeric cells of maternal origin in juvenile idiopathic inflammatory myopathies. Childhood Myositis Heterogeneity Collaborative Group. AB - We identified maternal microchimerism by fluorescence in-situ hybridisation in magnetically-separated CD4 or CD8 peripheral blood cells of eight of nine male patients with juvenile idiopathic inflammatory myopathy, compared with two of nine healthy male controls. We also found maternal microchimerism in inflammatory lesions (one skin sample and nine muscle biopsy samples) of all ten patients examined, compared with two of ten biopsy samples from patients with other muscle disorders. These results suggest that maternal cells may be involved in the pathogenesis of juvenile idiopathic inflammatory myopathy. PMID- 11191546 TI - Chimerism in children with juvenile dermatomyositis. AB - Juvenile dermatomyositis is a disease with similarities to chronic graft-versus host disease. To identify whether chimerism is present in juvenile dermatomyositis, we investigated the families of 15 children with the disorder. Chimerism was identified by PCR in 13 of the 15 affected children, compared with five of 35 siblings (p<0.0001). Maternal cells among peripheral-blood mononuclear cells were detected in 11 of the 15 boys, compared with five of 17 unaffected controls (p=0.02), and in muscle tissue of 12 of 15 compared with two of ten unaffected siblings (p=0.005). These results suggest that chimerism may be involved in juvenile dermatomyositis. PMID- 11191547 TI - Cytogenetics of myelodysplasia and acute myeloid leukaemia in aircrew and people treated with radiotherapy. AB - Increased risk of acute myeloid leukaemia has been reported in aircrew, possibly in association with cosmic radiation. We studied the cytogenetics of seven aircrew members who had acute myeloid leukaemia or myelodysplasia and found deletion or loss of chromosome 7 in four. The same abnormality was found in eight of 19 patients with leukaemia after radiotherapy alone. By comparison, only 81 of 761 unselected cases of myelodysplasia or acute myeloid leukaemia had the same cytogenetic abnormalities. Our results support the concept that deletions or loss of the long arm of chromosome 7 in myelodysplasia and acute myeloid leukaemia could indicate previous exposure to ionising radiation. PMID- 11191548 TI - Serogroup W135 meningococcal disease in Hajj pilgrims. AB - An outbreak of W135 meningococcal disease occurred in the spring of 2000 among pilgrims returning from Saudi Arabia and their contacts. Clinical isolates from England and France were examined and compared with reference strains from other countries. Characterisation of isolates by a range of typing methods showed them to be of clonal origin (ET-37) and closely related to other meningococci with an established propensity to cause disease clusters. A reappraisal of vaccination strategies for travellers is required. PMID- 11191549 TI - Outlook in oral and cutaneous Kaposi's sarcoma. AB - We looked at survival of 138 patients with HIV-1-associated Kaposi's sarcoma. Patients with lesions of the oral mucosa had a higher death rate (risk ratio 3.4 [95% CI 1.6-7.1]; p=0.001) than those having exclusively cutaneous manifestations of the disease. Patients with oral Kaposi's sarcoma and a CD4 cell count of at least 150/microL had a similar mortality risk to patients with the cutaneous disease but CD4 cell concentration of no more than 150/microL. Thus, oral Kaposi's sarcoma is an important prognostic marker, at least for patients who do not receive triple antiretroviral therapy. PMID- 11191550 TI - Alzheimer's amyloid hypothesis gains support. PMID- 11191551 TI - Have a healthy new year: easy to say, hard to do. PMID- 11191552 TI - Record spending on UK health, but still a long way to go. PMID- 11191553 TI - Court ruling favours Indian Navy's HIV policy. PMID- 11191554 TI - New report highlights negative health effects of UK asylum system. PMID- 11191555 TI - Canadian Act may mean greater access to personal medical records. PMID- 11191556 TI - Eraritjaritjaka. PMID- 11191557 TI - Silent pirates of the shore: Robert Louis Stevenson and medical negligence. PMID- 11191558 TI - Ancient Egyptian prosthesis of the big toe. PMID- 11191559 TI - Dr H C Bastian, scientific Jekyll and Hyde. AB - The neurological library of S A Kinnier Wilson, now in the Royal College of Physicians of Edinburgh, contains two books by Henry Charlton Bastian. Various forms of hysterical or functional paralysis (1893) is inscribed "To Dr Wilson by the Author, July 1906". Wilson was Bastian's house-physician at the time. The second book, given to Wilson's son by Bastian's daughter in 1940, is a lavishly illustrated tome, Studies in heterogenesis (1903). The two books testify to a scientific Jekyll and Hyde--one of the founders of neurology and a wildly unorthodox biologist. PMID- 11191560 TI - Hippocrates ridens: a 17th century medico-political journal. PMID- 11191561 TI - Pain after stapled haemorrhoidectomy. PMID- 11191562 TI - Pain after stapled haemorrhoidectomy. PMID- 11191563 TI - Pain after stapled haemorrhoidectomy. PMID- 11191564 TI - Pain after stapled haemorrhoidectomy. PMID- 11191565 TI - Pain after stapled haemorrhoidectomy. PMID- 11191566 TI - Pain after stapled haemorrhoidectomy. PMID- 11191567 TI - Pain after stapled haemorrhoidectomy. PMID- 11191568 TI - End-of-life decisions in neonatal intensive care. PMID- 11191569 TI - Interferon gamma gene in rheumatoid arthritis. PMID- 11191570 TI - Interferon gamma gene in rheumatoid arthritis. PMID- 11191571 TI - Jejunal ulceration and push enteroscopy. PMID- 11191572 TI - Industry-sponsored research. PMID- 11191573 TI - Industry-sponsored research. University of Pennsylvania Research Ethics Working Group. PMID- 11191574 TI - Myopia and its mechanisms. PMID- 11191575 TI - Global health status: two steps forward, one step back. PMID- 11191576 TI - Family support after stroke. PMID- 11191577 TI - Hodgkin's cylinder. PMID- 11191578 TI - Ethical, empirical, and epidemiological bases for action. PMID- 11191579 TI - Short-term spontaneous improvement rates in depressed outpatients. AB - The objectives of the present report were: a) to determine the spontaneous remission rate in depressed outpatients who do not receive antidepressant medication; b) to develop a novel method for obtaining a control group that can be used to gauge the effectiveness of antidepressant medication in clinical practice; and c) to compare response rates from the present sample with outcomes of depressed patients in our practice who were treated with antidepressant medications. By using a naturalistic design, prospective assessments were made on all depressed outpatients. Twenty-five patients who met full criteria for a major depressive episode ended up not taking antidepressant medication for a variety of reasons. "Response" rates to a no-treatment trial were determined with standard outcome criteria using the Clinical Global Impression-Improvement scale. Eight patients (32.0%) had a positive response, 5 patients (20.0%) had a partial response, and 12 patients (48.0%) were nonresponders to a no-treatment trial. These response rates were higher than expected, but significantly lower than what we had found in a cohort of depressed patients who underwent an antidepressant trial (p = .02). Likewise, treatment-resistant patients fared better on pharmacotherapy, though this difference was not statistically significant. These results suggest that the occurrence of spontaneous remissions may be common in clinical practice, and therefore the specific short-term benefits of antidepressant medication in clinical practice may frequently be overestimated. Despite the high rate of spontaneous remission in our sample, the present study allowed us to confirm the effectiveness of antidepressant medication in clinical practice using a novel method for obtaining a control comparison group. PMID- 11191580 TI - A brief assessment of psychosocial functioning of subjects with bipolar I disorder: the LIFE-RIFT. Longitudinal Interval Follow-up Evaluation-Range Impaired Functioning Tool. AB - Those afflicted with bipolar disorder often suffer from substantial functional impairment both when in episode and when in remission. This study examined the psychometric properties of a brief assessment of psychosocial functioning, the Range of Impaired Functioning Tool (LIFE-RIFT), among subjects with bipolar I disorder. The study sample consisted of 163 subjects who presented with bipolar I disorder at intake into the NIMH Collaborative Depression Study (CDS). All LIFE RIFT items come from the Longitudinal Interval Follow-up Evaluation (LIFE). Follow-up data that were used to examine the reliability and validity of the scale come from assessments of psychosocial functioning that were conducted 6, 12, 18, and 24 months after intake into the CDS. The results of factor analyses indicate that the scale items are measures of one construct, psychosocial functioning. The interrater agreement on the scale score was very good with an intraclass correlation coefficient was 0.94. The internal consistency reliability among the scale items was uniformly satisfactory over the four assessment periods, with coefficient alpha ranging from 0.78 to 0.84. Mixed-effect regression analyses showed that during mood episodes subjects were significantly more impaired than those in recovery. In conclusion, the psychometric properties of the LIFE-RIFT were examined in subjects with bipolar I disorder. The analyses from this longitudinal, observational study provide empirical support for the reliability and validity of the scale. The LIFE-RIFT provides a brief, inexpensive alternative to scales currently used to assess psychosocial functioning and can be easily added to semistructured assessments that are used in clinical and treatment outcome studies. PMID- 11191581 TI - Cognitive, mood, and functional evaluations using touchscreen technology. AB - We describe the design and development of the Cognitive Evaluation Protocol (CEP), a computer software program for evaluating cognitive and functional capacities and mood. The program is self-administered by subjects using touchscreen monitors for input. Stimuli in CEP subtests are randomized to reduce the effects of learning on repeated assessments. Findings demonstrate that a) minimum instruction is required for touchscreen use, even for computer-naive subjects; c) both normative subjects and psychiatric patients respond positively to self-administered evaluations; and c) CEP can be used for within-subject repeated evaluations with minimal distortion of results due to practice effects. The CEP Report Generator provides immediate printed performance results and creates a database for long-term digital storage and information use. PMID- 11191582 TI - Memory, attention, function, and mood among patients with chronic posttraumatic stress disorder. AB - We report a study of memory, attention, function, and mood among 36 male Vietnam War Veterans suffering from chronic posttraumatic stress disorder (PTSD). PTSD subjects (N = 36) were in good physical health, suffering from moderate depression, and not knowingly suffering from other mental disorders. Control subjects (N = 18) were in good physical health, not knowingly suffering from a mental disorder, and matched with PTSD subject for age, sex, and level of education. Assessment instruments for PTSD subjects included the PostTraumatic Stress Diagnostic Scale (clinician administered), the Hamilton Depression Rating Scale (clinician administered), and the Cognitive Evaluation Protocol (CEP), a touchscreen computer assessment instrument that is self-administered by subjects. CEP was administered twice to PTSD subjects 1 month apart; other instruments were administered at the beginning of the study. Control subjects took CEP once and were administered the Hamilton Depression Rating Scale and the PostTraumatic Stress Diagnostic Scale once. Compared with control subjects, PTSD subjects performed significantly less well on CEP for the three cognitive domains of attention, memory, and function and had highly elevated depression scores. An interaction between depression and memory was found but not with depression and attention. There was no evidence of reduced information processing speed among PTSD subjects. Comparisons between the three assessment instruments showed a high degree of cross-assessment agreement. The findings are consistent with reports that chronic PTSD is associated with compromised memory, attention, and function. The study documents the feasibility of using self-administrated touchscreen computer programs to evaluate and track features of mental disorders. PMID- 11191583 TI - Prosody impairment in depression measured through acoustic analysis. AB - This work attempts to explore the association between depression and prosody impairment through acoustic techniques of voice analysis. For this purpose, we selected 10 quantitative vocal parameters, obtained instrumentally, and related to the variability and psychomotor control of phonation, which we have considered as prosody indicators. The sample consisted of 23 patients with diagnosis DSM-III R of major depression and a control group of 20 healthy volunteers. We obtained results in 7 of the 10 acoustic parameters that suggest reduced prosody in depressed subjects. In a second voice test, carried out 2 months after baseline situation, and while patients were under antidepressant treatment, it was not possible to demonstrate that all these prosody indicators change to normality in those 13 subjects who clinically improved. PMID- 11191584 TI - Mental imagery and perception in hallucination-prone individuals. AB - College students screened for hallucination-proneness using the Launay-Slade Hallucination Scale (LSHS) were compared on measures of self-report vividness of imagery and on behavioral measures of imagery and perception (visual and auditory). Specifically, we tested the hypothesis whether hallucination-prone individuals would show smaller differences between imagery and perception performance, which may be indicative of increased sensory characteristics of mental images. We replicated earlier findings of higher self-report imagery ratings in the high hallucination-prone group. However, the two groups did not differ on five of six behavioral imagery-perception comparisons. On one visual task, hallucination-proneness was associated with larger imagery-perception differences. Our results reveal a dissociation between the level of subjective experience and the information processing level. Although vividness of mental images may be subjectively associated with mild hallucinatory experiences, we suggest that cognitive processes associated with reality discrimination rather than increased perceptual characteristics of mental images may play a role at the information processing level. PMID- 11191585 TI - British psychiatrists' attitudes toward optimal psychological functioning for men and women. PMID- 11191586 TI - Panic-free status is not associated with improvement on continuous measures in panic disorder. PMID- 11191587 TI - Interpersonal behavior and schizotypy. PMID- 11191588 TI - Memory for actions and dissociation in obsessive-compulsive disorder. PMID- 11191589 TI - 3rd World Congress of the International Society for Apheresis (ISFA). January 11 14, 2001. Taipei, Taiwan. Abstracts. PMID- 11191590 TI - Network therapy for addiction: bringing family and peer support into office practice. AB - Network therapy was developed as a specialized type of combined individual and group therapy to ensure greater success in the office-based treatment of addicted patients by using both psychodynamic and cognitive-behavioral approaches to individual therapy while engaging the patient in a group support network composed of family members and peers. This article outlines the role of group cohesiveness as a vehicle for engaging patients in this treatment; the patient's family and peers are used as a therapeutic network, joining the patient and therapist at intervals in therapy sessions. This network is managed by the therapist to provide cohesiveness and support, to undermine denial, and to promote compliance with treatment. The author presents applications of the network technique designed to sustain abstinence and describes means of stabilizing the patient's involvement. Some specific techniques discussed include ambulatory detoxification, disulfiram and naltrexone administration, relapse prevention, and contingency contracting. Also discussed are recent research on the use of psychiatric residents and counselors for treatment, and use of the Internet in dissemination. PMID- 11191591 TI - Reflections on group treatments as corrective experiences for addictive vulnerability. AB - This article addresses how and why groups help people with addictive disorders feel better and change. It advances the position that problems in self-regulation and the psychological suffering that ensues are at the root of addictive disorders. Group work is especially effective in addressing these problems, providing a means of relief, and examining co-occurring characterological problems. The evolution of these ideas and the generation of a model for group therapy for substance abusers are traced over a 30-year period, and a list of principles about how and why group treatments work is presented. In addition, a number of advantages that group psychotherapy has over 12-step programs for some patients are provided. Group psychotherapy is presented as a unique corrective emotional experience. PMID- 11191592 TI - Group therapy for victims of sexual abuse. PMID- 11191593 TI - Group psychotherapy of substance abuse in the era of managed mental health care. AB - The changes in health-care financing that have taken place over the last decade have spurred interest in finding innovative ways of delivering services at manageable cost levels. It comes as no surprise that increased interest and research have focused on group therapies as a major vehicle for reaching large numbers of people in need of psychological care that is brief, effective, and cost-efficient. More specifically, practitioners in the field of substance abuse have long recognized the value of group experiences as an integral part of the recovery and rehabilitative process. The influence of managed care to contain costs has added new incentives to expand the existing knowledge base in group treatment of addictions to comply with reduced funding and time constraints. PMID- 11191594 TI - Leader dilemmas and countertransference considerations in group psychotherapy with substance abusers. AB - Leader issues and countertransference dilemmas that emerge in psychotherapy groups for substance abusers will be examined along with strategies to extricate the therapist from the impasses that emerge. Specific issues include feelings of helplessness and inadequacy when a patient relapses and resumes substance use, countertransference reactions emanating from an overlapping personal or family history of substance abuse, countertransference helplessness when the therapist is more invested in the treatment than the patient, feelings of incompetence related to partial familiarity with 12-step culture and lingo, and countertransference devaluation fostered by systemic issues in substance abuse settings. PMID- 11191595 TI - Introduction to the special issue on group therapy and substance abuse. PMID- 11191596 TI - Addiction as an attachment disorder: implications for group therapy. AB - This article presents a perspective on addiction that not only substantiates why group therapy is the treatment of choice for addiction, but also integrates diverse perspectives from 12-step abstinence-based models, self psychology, and attachment theory into a complementary integrative formula. Attachment theory, self psychology, and affect regulation theory characterize addiction as an attachment disorder induced by a person's misguided attempt at self-repair because of deficits in psychic structure. Vulnerability of the self is the consequence of developmental failures and early environmental deprivation leading to ineffective attachment styles. Substance abuse, as a reparative attempt, only exacerbates that condition because of physical dependence and further deterioration of existing physiological and psychological structures. Prolonged stress on existing structures leads to exaggerated difficulty in the regulation of affect, which leads to inadequate modulation of appropriate behavior and self care and increased character pathology. PMID- 11191597 TI - Group psychotherapy for adolescents comorbid for substance abuse and psychiatric problems: a relational constructionist approach. AB - The group psychotherapy of adolescents comorbid for psychiatric and substance abuse problems is fraught with inconsistent attendance, frequent verbal and physical disruptions by the adolescents, and intense countertransference toward patients and their parents on the part of treating staff. A relational constructionist approach assists staff and patients in overcoming these obstacles and in focusing on the adolescents' search for personal meaning. Multiple group psychotherapy conducted in a combined day treatment and high school program is described and illustrated by case examples during the course of a year of treatment. These examples illustrate the importance of a relational non hierarchical approach to adolescent patients by treating staff. PMID- 11191598 TI - Tenth national congress of Italian Society of Phytochemistry (SIF). May 7-10, 2000, Florence, Italy. PMID- 11191599 TI - New insights in microchimerism: new topic for our journal? PMID- 11191601 TI - Bibliography. Current world literature. Assessment of nutritional status and analytical methods. PMID- 11191600 TI - Bibliography. Current world literature. Nutrition and the gastrointestinal tract. PMID- 11191602 TI - Acute thrombosis of limb arteries in horses with sepsis: five cases (1988-1998). AB - A hypercoagulable condition and poor perfusion to distal extremities might occur during equine endotoxaemic or septic shock, which could cause thrombosis of limb arteries. In our review, thrombosis occurred in neonatal foals in association with gram-negative bacteraemia. In 3 older foals and adults, thrombosis was associated with inflammatory bowel disease, diarrhoea and toxaemia. All patients had been treated with broad-spectrum antibiotics, nonsteroidal antiinflammatory drugs and i.v. crystalloid solutions. Two horses received i.v. hyperimmune plasma. A generalised coagulopathy was not suspected prior to clinical signs of distal limb necrosis, although thrombocytopenia occurred in 4 of the 5 cases at the time of, or shortly before, thrombosis. Thrombocytopenia, possibly due to platelets adherence to exposed subendothelial collagen, which induces contact activation of the intrinsic coagulation pathway, has been described in endotoxaemic horses and foals with gastrointestinal infectious or inflammatory diseases and disseminated intravascular coagulation. Activation of procoagulants by endotoxins, decreased blood flow to the limbs and endothelial damage, may have been responsible for a hypercoagulable condition leading to thrombosis in these 5 cases. The 3 enterocolitis patients may have had increased risk of thrombosis because of loss of antithrombin III, haemoconcentration and acidosis. PMID- 11191603 TI - Pituitary-independent Cushing's syndrome in a horse. PMID- 11191604 TI - The present state of equine dentistry. PMID- 11191605 TI - Age-related changes in the testes of horses. AB - Atrophy of seminiferous tubules and interstitial fibrosis are frequently observed in aged horses. Samples from 8 male Thoroughbreds, age 4-24 years, were subjected to histological, electron microscopical and immunohistochemical examination and statistical analysis. There were statistically significant increases in collagen fibres in the lamina propria of seminiferous tubules and testicular interstitium in 3 horses age 23 and 24 years compared with 5 horses age 4-20 years (P<0.001). Lamina propria surrounding atrophic tubules was thickened by an increase in collagen type IV and elastic fibres and by proliferation of bizarre myoid cells. Basal lamina was also thickened but had decreased reactivity for collagen type IV. Some myoid cells changed morphologically to a swollen and irregular shape and contained abundant cytoplasmic organelles. Laser scanning microscopy revealed that cytoplasmic actin filaments were decreased; the remaining filaments were positive for alpha-smooth muscle actin and vimentin, and matrix metalloproteinase 2 was secreted. These myoid cells transformed into myofibroblasts. The changes are interpreted as evidence of injured structure and function of the lamina propria and basal lamina and may explain the functional decline of the blood testis barrier. Myoid cells may play an important role in the progression of testicular fibrosis. PMID- 11191606 TI - Contact areas and pressure distribution on the proximal articular surface of the proximal phalanx under sagittal plane loading. AB - The objective of this study was to map topographically contact areas and pressure distributions on the proximal articular surface (PAS) of the proximal phalanx (PI) under various clinically relevant loading conditions. Left and right forelimbs of 13 mature horses were transected halfway down the radius and loaded in a position mimicking the weightbearing attitude close to the midstance phase. Five loads were used which corresponded with loads that can be expected in different gaits or during athletic performance (stance: 1800 N, walk: 3600 N, trot: 5400 N, gallop: 10,500 N and jumping: 12,000 N). Contact areas and pressure distributions at the PAS of PI were determined using a methylene blue dye staining technique and 2 pressure sensitive films (low pressure: range 2.5-10 MPa and medium pressure: range 10-50 MPa). The contact area of PI was positively correlated (r = 0.86; P<0.01) with the applied load. The contact area increased from 63% at 1800 N to 95% at 12,000 N and gradually shifted to include more of the edges of the articular surface, but especially the dorsal articular margin of PI. Pressure distribution patterns were similar under the different loading conditions. Pressure was less at the palmar margin and in the central depression and highest at the dorsal articular margin. With increasing load, the highest peak pressures were measured at sites of the dorsal articular margin that are not loaded in the standing or walking horse. The results of this study suggest that the frequent occurrence of osteochondral lesions at the dorsal articular margin of PI is caused by the combination of the intermittent character and the high absolute values of loads at this site as they occur during athletic performance. PMID- 11191607 TI - Repeatability of diagnostic ultrasonography in the assessment of the equine superficial digital flexor tendon. AB - A quantitative investigation of the variation that can occur during the course of ultrasonography of the equine superficial digital flexor tendons (SDFT) was undertaken. The aim of this investigation was to use an objective measure, namely the measurement of CSA, to quantify the variability occurring during the course of the ultrasonographic assessment of the equine SDFT. The effects of 3 variables on the CSA measurements were determined. 1) Image acquisition operator (IAc): two different operators undertaking the ultrasonographic examination; 2) image analysis operator (IAn): two different operators undertaking the calculation of CSA values from previously stored images; and 3) analytical equipment (used during CSA measurement) (IEq): the use of 2 different sets of equipment during calculation of CSA values. Tendon cross-sectional area (CSA) measurements were used as the comparative variable of 3 potential sources: interoperator, during image acquisition; interoperator, during CSA measurement; and intraoperator, when using different analytical equipment. Two operators obtained transverse ultrasonographic images from the forelimb SDFTs of 16 National Hunt (NH) Thoroughbred (TB) racehorses, each undertaking analysis of their own and the other operator's images. One operator undertook analysis of their images using 2 sets of equipment. There was no statistically significant difference in the results obtained when different operators undertook image acquisition (P>0.05). At all but the most distal level, there was no significant difference when different equipment was used during analysis (P>0.05). A significant difference (P<0.01) was reported when different operators undertook image analysis, one operator consistently returning larger measurements. Different operators undertaking different stages of an examination can result in significant variability. To reduce confounding during ultrasonographic investigations involving multiple persons, one operator should undertake image analysis, although different operators may undertake image acquisition. PMID- 11191608 TI - The hindlimb in walking horses: 1. Kinematics and ground reaction forces. AB - The objective was to study associations between kinematics and ground reaction forces in the hindlimb of walking horses. Video (60 Hz) and force (2000 Hz) data were gathered for 8 strides from each of 5 sound horses during the walk. Sagittal plane kinematics were measured concurrently with the vertical and longitudinal ground reaction forces. The hindlimb showed rapid loading and braking in the initial 10% stride. The stifle, tarsal and coffin joints flexed and the fetlock joint extended during this period of rapid loading. The vertical ground reaction force showed 2 peaks separated by a dip; this pattern was similar to the fetlock joint angle-time graph. Peaks in the longitudinal ground reaction force did not appear to correspond with kinematic events. Total braking impulse was equal to total propulsive impulse over the entire stride. Flexion and extension of the hip were responsible for protraction and retraction of the entire limb. Maximal protraction occurred shortly before the end of swing and maximal retraction occurred during breakover. During the middle part of stance the tarsal joint extended slowly, while the stifle began to flex when the limb was retracted beyond the midstance position at 28% stride. Flexion cycles of the stifle and tarsal joints were well coordinated during the swing phase to raise the distal limb as it was protracted. The results demonstrate a relationship between limb kinematics and vertical limb loading in the hindlimbs of sound horses. Future studies will elucidate the alterations in response to lameness. PMID- 11191609 TI - The hindlimb in walking horses: 2. Net joint moments and joint powers. AB - The objective of the study was to describe net joint moments and joint powers in the equine hindlimb during walking. The subjects were 5 sound horses. Kinematic and force data were collected synchronously and combined with morphometric information to determine net joint moments at each hindlimb joint throughout stance and swing. The results showed that the net joint moment was on the caudal/plantar side of all hindlimb joints at the start of stance when the limb was being actively retracted. It moved to the cranial/dorsal side around 24% stride at the hip and stifle and in terminal stance at the more distal joints. It remained on the cranial/dorsal side of all joints during the first half of swing to provide active limb protraction, then moved to the caudal/plantar aspect to reverse the direction of limb motion prior to ground contact. The hip joint was the main source of energy generation throughout the stride. It was assisted by the tarsal joint in both stance and swing phases and by the fetlock joint during the stance phase. The coffin joint acted as an energy damper during stance, whereas the stifle joint absorbed almost equal amounts of energy in the stance and swing phases. The coffin and fetlock joints absorbed energy as the limb was protracted and retracted during the swing phase, suggesting that their movements were driven by inertial forces. Future studies will apply these findings to detect changes in the energy profiles due to specific soft tissue injuries. PMID- 11191611 TI - International Workshop on Equine Chronic Airway Disease. Michigan State University 16-18 June 2000. PMID- 11191610 TI - Comparison of radiography and scintigraphy in the diagnosis of dental disorders in the horse. AB - Scintigraphy, with 99mTechnetium methylenediphosphonate (99mTc-MDP) and 99mTc labelled leucocytes, was compared to radiography in the diagnosis of dental disease in the horse in a prospective case-controlled study, comprising 30 horses with clinical signs of dental disease and 30 control horses. In each case, right and left lateral, ventral and dorsal soft tissue and bone phase scintigraphic images were obtained after i.v. injection of 1 GBq/100 kg bwt 99mTc-MDP, using a gamma camera. The same views were acquired in 10 horses with clinical signs of dental disease and 12 control horses after injection of 99mTc-labelled leucocytes. Standard radiographic projections of the paranasal sinuses and of the apices of the maxillary and mandibular teeth were obtained. The scintigraphs and radiographs were assessed subjectively by 2 board-certified surgeons and one board-certified radiologist, with extensive experience of equine radiology, from who the clinical history was withheld. Sensitivity, specificity and kappa, as a measure of agreement, were calculated for the different methods. Bone phase images were also scored subjectively on a scale from 0 to 3 on the basis of isotope uptake over the teeth. Regions of interest were defined over the teeth, and normal teeth compared to diseased counterparts. Total scintigraphic counts were related to the age of the animal and to the disease process. Differences in density ratios between left and right teeth were evaluated using the Mann-Whitney Test. Dental disease was confirmed in 22 horses at surgery or postmortem examination. Horses with dental disease showed a significant increase in scintigraphic activity over the affected tooth compared to the contralateral tooth, with a typical pattern for different diseases. The sensitivity of scintigraphy with 99mTc-MDP proved to be excellent (95.5%), whereas the specificity was moderate (86.4%). In contrast, radiography had excellent specificity (95.0%) and a low sensitivity (51.5%). The greatest sensitivity and specificity were achieved by evaluating radiographs and scintigrams together. The objective scintigraphic density ratios were found to be significantly different between diseased and control horses. The results of this study suggest that, if a density ratio of 1.5 or greater between a suspected diseased tooth and its contralateral number is regarded as abnormal, only 1% false positive diagnoses and 20% false negative diagnoses will occur. In contrast, scintigraphy with 99mTc labelled leucocytes was not very successful, due to the lack of anatomical detail provided by this technique, which made identification of the diseased tooth impossible. Accurate radiographic interpretation of dental disease presents difficulties, both in terms of missed diagnoses and mistaken diagnoses. Scintigraphy complements radiographic examination of dental structures by providing information important for accurate diagnosis and is, therefore, conceived to be essential for selection of the appropriate treatment for dental disease. PMID- 11191613 TI - The distribution of intratubular dentine in equine incisors: a scanning electron microscopic study. AB - The distribution of intratubular (peritubular) dentine was studied by scanning electron microscopy in 12 equine incisor teeth. High levels of intratubular dentine were found in the peripheral regions of the dentine. In these areas, a marked asymmetry occurred, as intratubular dentine was predominantly deposited onto the side of the dentinal tubular walls nearest to the dentino-enamel junction. The quantity and asymmetry of intratubular dentine were reduced towards the centre of the tooth. The significance of these variations in the amount and distribution of intratubular dentine between the different dentinal regions is discussed. PMID- 11191612 TI - Abdominal radiography in monitoring the resolution of sand accumulations from the large colon of horses treated medically. AB - This retrospective study consisted of 14 horses (age 6 weeks-12 years) with radiographically evident sand accumulations cranioventrally in the abdomen and clinical signs suggestive of sand enteropathy. The horses were treated medically and resolution of sand was monitored radiographically. Routine treatment consisted of psyllium mucilloid, combined with magnesium sulphate and/or mineral oilif needed. Initially, the number, size and shape of the sand accumulations showed large variation and the response to therapy was not predictable based on the initial appearance of the accumulation. In 2 foals, some of the sand was passed and the rest was mixed with other intestinal contents within 2-4 days. Even large accumulations disappeared in 2-4 days with psyllium alone or combined with mineral oil in 4 horses. In another 4 horses, the size of the accumulations decreased but varying amounts remained approximately at the same site, despite treatment for 1-4 weeks, and all these horses also had either gastric or large colon impaction. Three horses had a limited response to psyllium treatment, but the accumulation resolved with repeated doses of magnesium sulphate, with or without mineral oil. One horse did not respond to prolonged laxative treatment but the accumulation resolved on pasture. Clinical improvement was not necessarily related to the resolution of sand. Radiography of the cranioventral abdomen was found to be a useful means for monitoring the resolution of sand and confirming the effect of medical treatment in removing sand from the large colon in the horse. PMID- 11191614 TI - The radiographic development of the distal and proximal double contours of the equine navicular bone on dorsoproximal-palmarodistal oblique (upright pedal) radiographs, from age 1 to 11 months. AB - The aim of this study was to monitor the postnatal radiographic development of the proximal and distal double contours and the modelling of the shape of the proximal articular border. In mature horses, the proximal and distal contours of the navicular bone on dorsopalmar dorsoproximal-palmarodistal oblique (upright pedal) radiographs are commonly visualised as 2 lines, one being the articular border and the second representing the border of the cortex facing the deep digital flexor tendon (flexor border). The shape of the proximal articular border may be concave, undulating, straight or convex in the mature animal. These shapes have been found to be hereditary and to constitute a predisposing factor in the pathogenesis of navicular disease. This predisposing role may result from a shape dependent distribution of the biomechanical forces exerted on this region. There is no agreement in the literature with respect to the moment when the navicular bone takes its mature radiographic appearance. Upright pedal radiographs of the left front foot of 19 Dutch Warmblood foals were made at age 1 month and subsequently at intervals of 4 weeks, until the age of 11 months. The distal double contour developed soon after birth and the radiographic visibility of the articular border improved from ill-defined at 1 or 2 months to clear manifestation at 3 or 4 months. The proximal double contour developed later. The articular border became usually visible at age 3 or 4 months and was clearly visible from age 9 months. The mature shape of the proximal articular border usually became recognisable from age 7 months and was always obvious between 9 and 11 months. This development was associated with a gradual modelling of the lateral and medial extremities of the navicular bone. It was concluded that the navicular bone adopts its mature radiological appearance during the first year postpartum. Considering this early manifestation of the mature shape of the proximal articular border and its previously demonstrated inheritance, a force dependent development of this shape, as predicted by the trajectional theory/Wolffs law, is improbable. The predisposing role of this shape in the pathogenesis of navicular disease may therefore be explained by a shape-dependent distribution of the biomechanical forces exerted on the navicular bone. Considering the potential application of these findings, from age 1 year shape determination enables identification of the individual and breed susceptibility for the development of navicular disease. PMID- 11191615 TI - Effect of GnRH immunisation on hormonal levels, sexual behaviour, semen quality and testicular morphology in mature stallions. AB - The aim of this study was to investigate the effect of gonadotrophin-releasing hormone (GnRH) immunisation on mature stallions that had been used for breeding. Four Standardbred stallions were used in the study: 3 experimental animals and 1 control animal. Semen was collected regularly, i.e. twice/week, during the 4 months prior to the experimental period. The stallions were immunised against GnRH with a GnRH-BSA conjugate. Equimune was used as the adjuvant. The stallions were immunised on 5 occasions, 4 at 2 week intervals, and the fifth 4 weeks after the fourth. Blood samples were taken once a week for analysis of GnRH antibody titre and every third week for testosterone and oestrone sulphate analyses. Semen was collected once a week, and libido and sexual behaviour were observed. Ejaculate volume, sperm concentration, total number of sperm in the ejaculate, sperm motility and sperm morphology were evaluated. Testicular size was measured once a week. At the end of the study, the stallions were castrated, and a histological examination of the testes performed. All immunised stallions produced antibodies against GnRH, and plasma testosterone concentration decreased. However, the effect of immunisation varied between stallions. In 2 of the stallions, high levels of antibodies were found, while in the third, the level was moderate. Four weeks after the first immunisation, a decrease in libido was observed. Two months after the first immunisation, marked changes in semen quality were observed in the 2 stallions with high antibody titres. Fourteen weeks after the first immunisation, the total number of sperm/ejaculate had decreased from >8.6 x 10(9) to <2.7 x 10(9), sperm motility from >59 to <10% and the frequency of morphological normal spermatozoa had decreased from >60 to <14%. The dominating abnormalities were abnormal head shapes, proximal cytoplasmic droplets and detached heads. In the third stallion, only slight changes in semen quality were found. No changes were observed in the control stallion. Decreases in testicular size were noted in all of the experimental stallions. Pronounced histological alterations in the testes were observed in 2 of the stallions. It is concluded that the vaccine was effective in stimulating production of GnRH antibodies and in suppressing testicular function and androgen secretion. However, there was an individual variation in the responses among the stallions and, further, libido was not totally suppressed. PMID- 11191616 TI - Risk factors associated with hindlimb lameness and degenerative joint disease in the distal tarsus of Icelandic horses. AB - The aim of this study was to evaluate potential risk factors associated with hindlimb lameness and radiographic signs of degenerative joint disease (DJD) in the distal tarsus in Icelandic horses. The material consisted of riding horses (n = 420) age 6-12 years sired by 17 selected sires representing all major breeding lines, and of riding horses (n = 194) in the same age range sired by other sires. The examination protocol included the following: interview with owners/trainers, assessment of conformation, motion evaluation and radiographic examination. At the interview, data related to factors outside the horse (environmental variables) and data associated directly with the horse (intrinsic variables) were obtained. Data analysis was performed in 2 steps: screening using bivariate analysis, followed by testing with a multivariate logistic regression model. In the multivariate analysis, the factors of sire, age when broken to saddle and stud show participation were strongly associated with the prevalence of lameness. Height at the croup and ability to perform different gaits were also associated with the prevalence of lameness, but to a lesser degree. The risk factors of age, tarsal angle and birthplace were significantly associated with radiographic signs of DJD in the distal tarsus. Neither the variation in applied training intensity, the use of a professional or amateur trainer nor the temperament or front limb action of the individual horse was significantly associated with the prevalence of hindlimb lameness and/or radiographic signs of DJD in the distal tarsus in the Icelandic horse. PMID- 11191617 TI - Standing laparoscopic herniorrhaphy in stallions using cylindrical polypropylene mesh prosthesis. AB - Standing laparoscopic herniorrhaphy was performed in 9 stallions. Appropriate analgesia was achieved by sedation with detomidine and local flank infiltration with mepivacaine. Three portal sites at the paralumbar fossa were used to perform the herniorrhaphy by means of triangulation. A cylindrical polypropylene mesh was inserted and fixated in the inguinal canal. Subsequent adhesion formation resulted in an obliterated inguinal canal within 2 weeks. This minimal invasive technique allowed us to perform a testis sparing herniorrhaphy in the standing horse. PMID- 11191618 TI - Effect of water restriction on equine behaviour and physiology. PMID- 11191619 TI - Dental dysplasia and oligodontia in a thoroughbred colt. PMID- 11191620 TI - The ribonucleotide reductase inhibitor trimidox induces c-myc and apoptosis of human ovarian carcinoma cells. AB - Trimidox (3,4,5-trihydroxybenzohydroxamidoxime), a recently synthesized inhibitor of ribonucleotide reductase (RR), was shown to exert anti-proliferative activities in HL-60 and K562 human leukemia cell lines and to prolong the life span of mice inoculated with L1210 mouse leukemia cells. Here we test whether trimidox also exhibits anti-neoplastic properties in ovarian carcinoma cells. Since the mode of action of trimidox on cell fate has not been investigated so far, we addressed this unresolved item and find that this polyhydroxybenzoic acid derivative induces apoptosis of N.1 human ovarian carcinoma cells when tested in growth factor deprived medium. Utilizing an improved analysis, based on Hoechst 33258/propidium iodide double staining, apoptosis is quantified and discriminated from necrosis. Trimidox induces c-myc expression, which is indispensible for apoptosis of N.1 cells, and expression of plasminogen activator/urokinase type (upa), which supports the apoptotic process under more physiological conditions. Surprisingly, trimidox does not block dNTP synthesis in N.1 cells at the concentrations tested and, therefore, trimidox induces apoptosis independent of RR-inhibition. Like TNFalpha or benzamide riboside, which are also inducers of apoptosis of N.1 cells, trimidox also down-regulates the G1 cell cycle phosphatase cdc25A, whereas cyclin D1 becomes up-regulated. This report shows that trimidox destroys human ovarian carcinoma cells by inducing them to undergo apoptosis as well as corroborating previous investigations which demonstrated that apoptosis of these cells depends on c-myc over-expression when survival factors are withdrawn. PMID- 11191621 TI - Studies on the involvement of histamine in the hypothalamic-pituitary-adrenal axis activation induced by nerve growth factor. AB - Nerve growth factor (NGF) has been shown to stimulate the hypothalamic-pituitary adrenocortical (HPA) axis. Since NGF induces the release of histamine from mast cells and in consideration of the fact that histamine is an HPA axis activator, we investigated whether NGF adrenocortical stimulation is mediated by histamine. To accomplish with it, the H1 histamine antagonist promethazine and the H2 antagonists metiamide and zolantidine were used in freely-moving cannulated rats. The increase in plasma corticosterone concentration induced by histamine administration was prevented completely by promethazine pretreatment but was unaffected by the H2 antagonists. Neither H1 nor H2 antagonists affected the adrenocortical stimulation induced by NGF administration. Moreover, since mast cells are reportedly present in the rat adrenal gland and the locally released histamine mediates the release of adrenaline which, in turn, stimulates glucocorticoid synthesis and secretion, we studied the effect of NGF on basal and ACTH-stimulated corticosterone release from in vitro isolated quartered adrenal glands and collagenase-dispersed adrenal cells. The results from these in vitro experiments have indicated that NGF modified neither spontaneous nor stimulated corticosterone release. Altogether these observations suggest that endogenous histamine is unlikely to be involved in HPA axis stimulation by NGF and reinforce the previously proposed concept of an active participation of NGF in the control of adrenocortical activity. PMID- 11191622 TI - Chronic losartan treatment decreases angiotensin II-mediated facilitation of noradrenaline release in the caudal artery of spontaneously hypertensive rats. AB - Sympathetic activity is modulated by angiotensin II (AII), both at pre- and postsynaptic level in the rat caudal artery. In the spontaneously hypertensive rat (SHR), this artery receives more dense sympathetic innervation than blood vessels of normotensive strains. This fact seems to be linked to the enhanced pressor responses elicited by noradrenaline in SHR. In this work we describe, in the SHR, the effect of a chronic treatment with the angiotensin II AT1-receptor antagonist, losartan, in modulating noradrenergic mechanisms involved in caudal artery contraction. The effect of losartan is compared to that of captopril, given at doses leading to a similar decrease of both arterial blood pressure and left ventricular hypertrophy. The contractile response of caudal artery rings induced by endogenous noradrenaline released by low frequency transmural nerve stimulation (TNS) has been studied. Under our conditions, TNS (0.5-1 Hz) induced higher contractile responses in SHR treated with losartan than in the control and captopril-treated groups. This difference seems to be due to an increase of the postsynaptic effect of noradrenaline (NA) rather than to an increase of noradrenaline release from sympathetic endings, since i) DE50 value for NA was lower in losartan-treated SHR than in the other groups, and ii) AII induced a dose-dependent increase of TNS-evoked release of radioactivity from caudal artery segments loaded with [3H]-NA, in both control and captopril-treated groups but had no effect in the losartan-treated group. These results show that chronic treatment with losartan, although slightly enhancing the pressor effect of NA at postsynaptic level, fully supresses the facilitatory role of AII on NA release. PMID- 11191623 TI - Nifedipine and nisoldipine modulate membrane potential of vascular endothelium via a myo-endothelial pathway. AB - Effects of nifedipine (Nif) and nisoldipine (Nis), dihydropyridine Ca2+ channel blockers (DHPs) on membrane potential and currents of endothelial cells, which are enzymatically dispersed (dis-ECs) from or exist in arterial segments (seg ECs) of rabbit and rat aorta, were examined. Outward currents induced by 1-10 microM acetylcholine (ACh) in dis-ECs were neither affected by a receptor operated Ca2+ channel blocker, SK&F 96365 (SKF), nor DHPs. ACh hyperpolarized dis ECs and seg-ECs by 15-20 mV, whereas phenylephrine (Phe) elicited oscillatory depolarization in seg-ECs but not in dis-ECs. The Phe-induced response in seg-ECs was significantly inhibited by treatment with 18beta-glycyrrhetinic acid, a disrupter of gap junctions. Application of 0.3 microM Nif or Nis effectively inhibited the Phe-induced oscillatory depolarization, while these DHPs did not affect ACh-induced hyperpolarization in seg-ECs. The lack of effect on dis-ECs indicates that DHPs have little effect on dis-ECs themselves, nevertheless DHPs inhibit the Phe-induced endothelial potential oscillation which is conducted from smooth muscle cells via a myo-endothelial pathway. PMID- 11191624 TI - Chronic stress influences the immune system through the thyroid axis. AB - The aim of the present work was to analyze the effect of chronic stress on thyroid axis and its influence on the immune response. For this purpose a murine model of chronic stress was developed to evaluate and to correlate thyroid hormone levels with humoral alloimmune response. Results show a reduction in serum levels of thyroid hormones, specially a significant decrease in serum levels of triiodotyronine (T3) in stressed animals. On the other hand, alloimmunization was not able to induce an early increment in T3 and thyroxine (T4) levels as it was previously reported in normal animals. In addition, lower titers of alloantibodies were obtained in animals under stress conditions as compared to normal mice. The sustitutive T4 treatment in stressed animals increased significantly alloantibody production as well as the early increment in thyroid hormones after antigenic challenge. These findings suggest that chronic stress induces an alteration of the function of thyroid axis that alters the immune response. PMID- 11191625 TI - Interaction of ascorbate and alpha-tocopherol enhances antioxidant reserve of erythrocytes during anemia in visceral leishmaniasis. AB - Visceral leishmaniasis (V.L.) is associated with enhanced lipid peroxidation along with impaired function of antioxidant defense system in erythrocytes. The effect of chronic treatment with ascorbate and alpha-tocopherol was studied on erythrocytes in hamsters infected with Leishmania donovani. Combination treatment with both antioxidants proved to be a potential suppressor of lipid hydroperoxide formation as well as hypotonic osmotic lysis during the leishmanial infection. Positive correlations between the depleted levels of erythrocyte ascorbate, GSH and alpha-tocopherol exhibit proportionate alterations in the nonenzymatic antioxidant levels at different stages of infection. Indirect measurement of transmembrane electron transfer as ferricyanide reduction suggests an active participation of endogenous contents of ascorbate and alpha-tocopherol in the protection against oxidative damage of membrane lipids. Cooperative behavior of both antioxidants in the ferricyanide reducing capacity was further evinced by resealing the ghosts in presence of exogenous ascorbate and alpha-tocopherol. Furthermore, intravesicular ascorbate serves in the defense of extravesicular ferricyanide induced oxidation of endogenous alpha-tocopherol. The results suggest an interacting role of ascorbate and alpha-tocopherol in maintaining the antioxidant reserve of erythrocytes during anemia in V.L. PMID- 11191626 TI - Post-transcriptional inhibition of glutamine synthetase induction in rat liver epithelial cells exerted by conditioned medium from rat hepatocytes. AB - Recently, a soluble factor produced by primary periportal hepatocytes and different from glutamine was found to completely block induction of glutamine synthetase (GS) by dexamethasone (DEX) in the liver cell line RL-ET-1G. Using Northern and Western blotting we investigated whether this block is regulated on the transcriptional or the post-transcriptional level. Three different species of GS mRNA were detected that all increased (though in different proportions), when the cells were exposed to DEX for 24 h. Further maintenance for another 24 h in normal DEX-containing culture medium, conditioned medium from primary periportal hepatocytes or medium containing glutamine did not result in significant differences in GS mRNA levels. In contrast, GS protein and specific GS-activity remained high only under normal culture conditions, whereas both returned to basal levels in conditioned and glutamine-supplemented culture medium. Throughout, GS protein content and specific GS-activity strongly correlated (r = 0.98) excluding that GS-activity is regulated by chemical modification. These data suggest that the decrease in enzyme activity caused by cultivation in CM is controlled on the post-transcriptional level. PMID- 11191627 TI - Structurally dissimilar proteins with antiviral and antifungal potency from cowpea (Vigna unguiculata) seeds. AB - Evidence is presented for the existence of multiple proteins with antifungal and antiviral potency in cowpea seeds. The two proteins, designated alpha- and beta antifungal proteins in accordance with their order of elution from the CM Sepharose column, were capable of inhibiting human immunodeficiency virus (HIV) reverse transcriptase and one of the glycohydrolases associated with HIV infection, alpha-glucosidase, but beta-glucuronidase was not repressed. The ability of the proteins in retarding mycelial growth of a variety of fungi was also demonstrated with alpha-antifungal protein being more potent in most of the cases. Beta-antifungal protein was more active in only one instance. Both antifungal proteins had low cell-free translation-inhibitory activity. The proteins were adsorbed on Affi-gel blue gel-and CM-Sepharose but could be separated from one another during chromatography on the latter medium by means of a linear NaCl concentration gradient. Different molecular weights were exhibited by the proteins, being 28 kDa and 12 kDa respectively for alpha- and beta- antifungal proteins. Alpha-antifungal protein was characterized by an N-terminal sequence showing close resemblance to sequences of chitinases. Beta-antifungal protein exhibited an N-terminal sequence hitherto unknown in the literature. PMID- 11191628 TI - Ca2+/calmodulin mediated pathways regulate the uptake of L-DOPA in mouse neuroblastoma neuro 2A cells. AB - The present study examined the involvement of protein kinase A (PKA), protein kinase G (PKG), protein kinase C (PKC), protein tyrosine kinase (PTK) and Ca2+/calmodulin mediated pathways on the uptake of L-DOPA through the L-type amino acid transporter in Neuro 2A cells, an in vitro model of neuronal cells. Non-linear analysis of the saturation curve for L-DOPA revealed a Km value (in microM) of 54+/-2 and a Vmax value (in nmol mg protein/6 min) of 34+/-1. L-DOPA uptake was a sodium-independent process and insensitive to N-(methylamino) isobutyric acid (MeAIB, 1 mM), but sensitive to 2-aminobicyclo(2,2,1)-heptane-2 carboxylic acid (BHC, IC50=82 microM). The Ca2+/calmodulin inhibitors calmidazolium and trifluoperazine inhibited L-DOPA (2.5 microM) uptake with IC50's of 33 and 105 microM, respectively. The inhibitory effect of BHC on the accumulation of L-DOPA was of the competitive type, whereas that of calmidazolium and trifluoperazine was of the non-competitive type. Modulators of PKA (cyclic AMP, forskolin, isobutylmethylxanthine and cholera toxin), PKG (cyclic GMP, zaprinast, LY 83583 and sodium nitroprusside), PKC (phorbol 12,13-dibutirate, phorbol 12-myristate 13-acetate and chelerythrine) and PTK (genistein and tyrphostin 25) failed to affect the accumulation of a non-saturating (2.5 microM) concentration of L-DOPA. It is concluded that L-DOPA uptake in Neuro 2A cells is promoted through the L-type amino acid transporter and appears to be under the control of Ca2+/calmodulin mediated pathways. PMID- 11191629 TI - P38 MAPK, but not p42/p44 MAPK mediated inducible nitric oxide synthase expression in C6 glioma cells. AB - Recently mitogen-activated protein kinase (MAPK) has been reported to play an important role in phosphorylation cascades governing cell growth and protein expression in numerous cell types. In order to explore the signaling mechanism by which inducible nitric oxide synthase (iNOS) is regulated in C6 glioma cells, we investigated the role of MAPK in iNOS expression by using the specific MAPK inhibitors. First the induction of nitric oxide by lipopolysaccharide (LPS), tumor necrosis factor alpha (TNFalpha), interferon gamma (IFNgamma), alone or their combination, was studied in C6 glioma cells. Administration of LPS, TNFalpha, or IFNgamma alone had no detectable stimulatory effect on the production of nitric oxide (NO). However, combination of the three factors elicited a significant elevation of NO level in C6 cell culture medium. Subsequently pretreatment of C6 cells with a specific inhibitor of p38 MAPK, SB202190, resulted in a dose-dependent inhibition of NO production and iNOS expression, but PD98059, an inhibitor of p42/p44 MAPK activation, had no effect. These data suggest that p38 MAPK mediates iNOS expression in C6 glioma cells, but p42/p44 MAPK is not involved in this process. PMID- 11191630 TI - Polynitroxyl albumin plus tempol attenuates liver injury and inflammation after hepatic ischemia and reperfusion. AB - PNA+Tempol, albumin containing conjugated (polynitroxyl albumin; PNA) and free (4 hydroxyl-2,2,6,6-tetramethyl-piperidinyl-1-oxyl; Tempol) nitroxide may protect against injury caused by reactive oxygen species. Therefore, the actions of PNA+Tempol on liver injury and inflammation induced by hepatic ischemia and reperfusion (I/R) were examined. Rats were subjected to 1 h ischemia followed by 24 h reperfusion in the absence (I/R) or presence of PNA+Tempol (25%; 15 mL/kg, i.v.) (I/R+PNA+Tempol) or human serum albumin (23%; 13.5 mL/kg, i.v.) (I/R+HSA). Test solutions were administered prior to and for 2 h during reperfusion. Sham operated rats underwent surgery with neither ischemia nor infusion. I/R+PNA+Tempol rats had significantly less liver injury and inflammation than I/R rats. I/R+PNA+Tempol livers exhibited focal lesions whereas I/R livers exhibited global necrosis. Likewise, plasma ALT activity was significantly lower in I/R+PNA+Tempol rats. PNA+Tempol reduced I/R-induced neutrophil accumulation and intercellular adhesion molecule-1 (ICAM-1) expression. HSA did not alter I/R induced liver injury or inflammation. Sham-operated rats exhibited normal liver morphology and no inflammation. Attenuation of I/R liver injury by PNA+Tempol may be mediated by its effect on inflammation, the major contributor to I/R injury. Reduction of inflammation by PNA+Tempol is most likely due to the antioxidative nature of the nitroxides. PMID- 11191631 TI - ALEPH-2, a suspected anxiolytic and putative hallucinogenic phenylisopropylamine derivative, is a 5-HT2a and 5-HT2c receptor agonist. AB - To assess the pharmacodynamic profile of ALEPH-2, a phenylisopropylamine derivative with alleged anxiolytic and hallucinogenic properties, Xenopus laevis oocytes were microinjected with either of the rat cRNA for the 5-HT2A or the 5 HT2C receptor. Concentration-response curves were obtained following the exposure of the oocytes to varying concentrations of either ALEPH-2 or 5-hydroxytryptamine (5-HT) for 10 s. ALEPH-2 is a partial agonist on the 5-HT2A receptor with a similar potency to 5-HT. In contrast, ALEPH-2 is a full 5-HT2C receptor agonist and is about 15-fold less potent than 5-HT. Pre-application of 1 microM ritanserin antagonized the responses induced by 5-HT and ALEPH-2 to the same extent; however, the 5-HT2A receptor is more sensitive to ritanserin blockade than the 5-HT2C receptor. PMID- 11191632 TI - ATP as a presynaptic modulator. AB - There is considerable evidence that ATP acts as a fast transmitter or co transmitter in autonomic and sensory nerves mostly through activation of ionotropic P2X receptors but also through metabotropic P2Y receptors. By analogy, the observations that ATP is released from stimulated central nervous system (CNS) nerve terminals and that responses to exogenously added ATP can be recorded in central neurons, lead to the proposal that ATP might also be a fast transmitter in the CNS. However, in spite of the robust expression of P2 receptor mRNA and binding to P2 receptors in the CNS, the demonstration of central purinergic transmission has mostly remained elusive. We now review evidence to suggest that ATP may also act presynaptically rather than solely postsynaptically in the nervous system. PMID- 11191633 TI - Adhesion molecules on peripheral blood lymphocyte subpopulations in the elderly. AB - Adhesion molecules, such as CD49d, CD50 and CD62L, have important roles in many adhesive interactions involving cells of the immune system. Since it has been shown that many immunological alterations are present in aged subjects, we studied, by means of triple colour whole blood immunostaining and multiparametric flow cytometry, the expression and intensity level (MFI) of these molecules on peripheral blood lymphocyte subpopulations from 23 healthy elderly subjects and 13 young controls. In the elderly a decrease in total peripheral blood lymphocytes bearing CD62L antigen was observed (39 +/- 13% vs 63 +/- 6% and 745 +/- 312/mm3 vs 1,393 +/- 407/mm3; p<0.001), whereas the numbers of lymphocytes expressing CD49d and CD50 antigens were comparable in aged and young subjects. In addition, CD50 and CD62L MFI values on total peripheral blood lymphocytes were higher in elderly than in young subjects (5.23 +/- 1.03 vs 4.18 +/- 0.44, p = 0.001 and 2.60 +/- 0.35 vs 2.21 +/- 0.40, p = 0.005 respectively) while the intensity expression of CD49d was unchanged. The percentages and absolute numbers of T and B lymphocytes expressing CD62L were decreased in elderly compared to young subjects (CD62L+CD3+: 43 +/- 15% vs 66 +/- 9% and 581 +/- 257/mm3 vs 1,028 +/- 418/mm3, p<0.001; CD62L+CD19+: 78 +/- 12% vs 90 +/- 4%, p < 0.005 and 103 +/- 64/mm3 vs 207 +/- 98, p < 0.001). A decrease in the proportion of CD62L bearing NK cells was also observed in the elderly (25 +/- 14% vs 46 +/- 24%, p<0.005), although their absolute number was unchanged. No significant differences were detected in the proportion of T, B and NK lymphocytes expressing CD49d and CD50 antigens and only the absolute numbers of B cells expressing these adhesion molecules were lower in elderly (CD49d+CD19+: 121 +/- 71/mm3 and CD50+CD19+: 107 +/- 73/mm3) compared to young donors (CD49d+CD19+: 248 +/- 112/mm3 and CD50+CD19+: 235 +/- 120/mm3, p < 0.001). Moreover, the intensity of adhesion molecule expression was differentially modulated in the elderly depending on the specific lymphocyte cell population considered. The densities of CD49d, CD50 and CD62L antigens on B and NK lymphocytes from the two age groups were not different; on the contrary, T lymphocytes from elderly donors exhibited increased CD49d (1.69 +/- 0.09 vs 1.62 +/- 0.07, p < 0.05), CD50 (4.98 +/- 1.16 vs 3.77 +/- 0.46, p < 0.001) and CD62L (2.26 +/- 0.38 vs 1.99 +/- 0.37, p < 0.05) MFI values compared to young donors. PMID- 11191634 TI - Effect of resveratrol on intimal hyperplasia after endothelial denudation in an experimental rabbit model. AB - The ability of resveratrol to inhibit vascular intimal thickening was tested in an experimental model in which endothelial denudation was performed in the normal rabbit iliac artery. Resveratrol (2 approximately 4mg/ kg/d) was administered intragastrically for 5 weeks beginning 1 week before denudation. At the higher concentration of resveratrol, the intimal hyperplasia of injured vascular wall was effectively inhibited; the intimal proliferation index also was significantly less than that in the untreated control group (0.28 +/- 0.07 vs 0.41 +/- 0.13, respectively, p<0.01); the relative luminal area increased from 0.38 +/- 0.06 in the untreated control group to 0.53 +/- 0.10 in the resveratrol treatment group (p < 0.001); and the count of smooth muscle cells in the thickened intima was statistically significantly reduced in the high dose resveratrol treatment group than that in the untreated group (1,115 +/- 510 vs 1,796 +/- 963, respectively, p < 0.05). Resveratrol added to the culture media of cultured rabbit vascular smooth muscle cells inhibited DNA synthesis in a dose-dependent manner. These results showing that resveratrol is capable of inhibiting intimal hyperplasia of injured artery raise the possibility that this polyphenol might have clinical potential in prevention and treatment of restenosis after angioplasty. PMID- 11191635 TI - Molecular mechanisms involved in the antiproliferative action of protein tyrosine phosphatase inhibitor potassium bisperoxo(1,10-phenanthroline)oxovanadate. AB - Potassium bisperoxo(1,10-phenanthroline)oxovanadate, bpV(phen), a powerful protein phosphotyrosine phosphatase inhibitor and a potent insulinomimetic, influenced three fundamental cellular processes in HL-60 human leukemic cells: 1) inhibition of proliferation, 2) induction of differentiation and 3) apoptotic cell death. In the presence of micromolar concentrations of bpV(phen) cell number and DNA synthesis decreased progressively with time of incubation. A single treatment with bpV(phen) (3 microM) activated a differentiation program; after 6 days of incubation 82% of cells were differentiated, but differentiation started already within the first 24 h. Concentrations of 5-10 microM bpV(phen) caused the characteristic DNA ladder pattern, starting after 4.5 h. Differentiation in HL-60 cells appear to be associated with activation of extracellular signal-regulated kinase while apoptosis is connected with phosphorylation and activation of both extracellular signal-regulated kinase and c-Jun N-terminal kinase in a concentration and time-dependent manner. The antiproliferative and apoptotic action of bpV(phen) could be exploited in combination chemotherapy in leukemia. PMID- 11191636 TI - Rostral ventrolateral medulla catechol involvement upon sino-aortic deafferentation: an in vivo voltammetric study. AB - Pharmacologically-induced hypertension engages few aminergic ventrolateral medullary cells. To further address this issue, reflex hypertension evoked by acute sino-aortic deafferentation was chosen as a model. Adrenergic rostral ventrolateral neurons were recorded with a continuous, catechol-specific tool, i.e. in vivo voltammetry. Controlled hypotension led to the expected increase in catechol signal in sham rats (n = 4) but not in deafferented (vagi, superior laryngeal and glossopharyngeal nerves) rats (n = 5). Thus, the central responsiveness to known stimuli remained intact in this preparation following acute sino-aortic deafferentation. However, acute sino-aortic deafferentation itself induced no increase in catechol signal (n = 4 or 5 respectively). No increase in catechol signal was, observed when deafferentation was performed a) under hyperoxic conditions (O2 = 100%, n = 5) b) by extensive deafferentation involving also the cervical sympathetic trunk under halothane (n = 5) c) upon restrictive deafferentation leaving the vagi intact under pentobarbital (n = 5) d) in decerebrate animals (n = 4). Adrenergic rostral ventrolateral medullary barosensitive bulbospinal neurons may be primarily involved during hypotension. PMID- 11191637 TI - A study of iodothyronine 5'-monodeiodinase activities in normal and pathological tissues in man and their comparison with activities in rat tissues. AB - The present study was undertaken to investigate the peripheral iodothyronine 5' monodeiodination in different human and rat tissues. We studied iodothyronine 5' monodeiodinase type I (5'-DI) activity in liver, kidney, intestine, right cardiac atrium and skeletal muscle and we compared the results with those in rat tissues. Lodothyronine 5'- monodeiodinase type II (5'-DII) activity was studied in normal and ischemic human heart and in rat normal myocardium and brain. The 5'-DI activity (fmol/min x mg protein) in liver and kidney was significantly higher (p < 0.001, ANOVA) in normal rat tissue than in human. However, no significant differences were observed in 5'-DI activity between normal and tumoral human intestine or between intestinal tissue of man and rat. 5'-DI activity in normal human skeletal muscle was significantly higher than that in rat skeletal muscle (p < 0.05). The 5'-DI activity was lower in human ischemic myocardium when compared to normal myocardium either in humans (p < 0.05) or rat (p < 0.001). The Km of 5'-DI was significantly lower in rat than in human kidney and liver (p < 0.05). We conclude that 1) 5'-DI is distributed widely among extrathyroidal human and rat tissues and 5'-DII activity is detectable both in human and rat heart; 2) 5'-DI activity in liver and kidney is lower in man than in rat; 3) 5'-DI activity in the skeletal muscle is higher in man than in the rat; 4) 5'-DI activity is decreased in tumoral tissues of human liver and kidney and in ischemic myocardium, while no significant difference was found between human and rat cardiac 5'-DII activity. PMID- 11191638 TI - Negative relationships between erythrocyte Ca-pump activity and lead levels in mothers and newborns. AB - Lead poisoning induces hematological, gastrointestinal and neurological dysfunctions. One of the potential mechanisms is the inhibition of calcium-pump (Ca-pump), a transport protein. We investigated the effects of an environmental low lead exposure on Ca-pump activity in 247 mothers and their newborns. Maternal and cord blood, and newborn and mother hair, were sampled at delivery. Geometric means for mother and cord blood lead (Pb-B), and for mother and newborn hair lead (Pb-H), were 6.3 and 4.8 microg/dl, and 1.7 and 1.1 microg/g. Means for mother and cord basal Ca-pump activities were 2,442 and 2,675 nM/mg/hr. Mother enzymatic activity was negatively related to her Pb-B and Pb-H and to the cord Pb-B and newborn Pb-H levels. Newborn enzymatic activity was negatively related to his Pb H level only. Adjustment for gestational age, child's sex, mother's age at delivery, alcohol, coffee and tea consumption, and smoking habits during pregnancy did not modify these relationships. Our findings support the hypothesis that lead toxicity could be in part mediated by a reduction of Ca-pump activity. This effect could be observed at low environmental exposure, in mothers and newborns. PMID- 11191639 TI - Combined supplementation of vanadium and 1alpha,25-dihydroxyvitamin D3 inhibit placental glutathione S-transferase positive foci in rat liver carcinogenesis. AB - The combined effects of vanadium (V) and 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] in inhibiting diethylnitrosamine (DEN)-induced and phenobarbital (PB) promoted hepatocarcinogenesis were examined in male Sprague-Dawley rats. All the rats were subjected to 70% partial hepatectomy (PH) at week 4 and 24h later were administered either solvent trioctanoin (Group B, D, F and H) or 10 mg DEN/kg (Group A, C, E and G) by gavage. Briefly after two weeks of DEN administration, PB were administered (0.05% in basal diet) to all the DEN-treated rats and continued till the completion of the experiment. Supplementary V at the dose of 0.5 ppm in drinking water ad libitum (Group C and D), 1,25(OH)2D3 at the dose of 3 microg/ml in propylene glycol per os twice a week (Group E and F) or both V and 1,25(OH)2D3 at the same above given doses (Group G and H) were started 4 weeks prior to DEN administration (week 0) and continued thereafter till week 15. The expression of the number and area of altered hepatocyte foci (AHF) positive for placental glutathione S-transferase (GST-P) was maximum in DEN treated and PB promoted group (Group A). V (Group C) and 1,25(OH)2D3 (Group E) treatment significantly reduced the expression of GST-P-positive hepatocytes by 36.02% and 45.16% respectively but an additive protective action (61.46%) was found in Group G which received both V and 1,25(OH)2D3 for the entire period of the study. Moreover, histopathological examination and the incidence of hepatic hyperplastic nodules showed that combined action of V and 1,25(OH)2D3 can able to minimize the appearance of nodules as well and maintain the normal cellular architecture than V and 1,25(OH)2D3 when given alone. These results suggest that, when given together V and 1,25(OH)2D3 could be the chemopreventive agents for rat liver carcinogenesis. PMID- 11191640 TI - In vitro pharmacological profile of peptide III-BTD: a novel ligand for nociceptin/orphanin FQ and opioid receptors. AB - Peptide III-BTD has been recently identified as a non-selective nociceptin/orphanin FQ receptor ligand by screening of a synthetic peptide combinatorial library. In the present study we evaluated the pharmacological profile of peptide III-BTD in isolated tissues (mouse and rat vas deferens, guinea pig ileum) sensitive to both nociceptin and opioid peptides. In the mouse vas deferens and guinea pig ileum, III-BTD concentration dependently inhibited the electrically induced twitch (pEC50 5.91 and 6.18, respectively; Emax 94 +/- 1% and 94 +/- 2%) and this effect was blocked by naloxone (1 microM). In the rat vas deferens, III-BTD was inactive in most of the tissues, while in few others it elicited a slight inhibition only at the highest concentration tested (10 microM). In the presence of 1 microM naloxone, 1 microM III-BTD shifted to the right the concentration response curve of nociceptin in a parallel manner, showing pKB values in the range 6.6-6.9. These data confirm on native nociceptin receptors the pharmacological profile of peptide III-BTD which behaved as a mixed nociceptin receptor antagonist/opioid receptor agonist in the [35S]GTPyS binding assay performed on cells expressing the recombinant human receptors. PMID- 11191641 TI - Structure and function of Toll-like receptor proteins. AB - Beginning in 1997 with the identification of the first human homologue of the Drosophila protein Toll, a family of related molecules have been identified in both humans and other mammals. These Toll-like receptor (TLR) proteins appear to represent a conserved family of innate immune recognition receptors. TLR proteins share extended homology with receptors for the cytokines interleukin 1 (IL-1) and interleukin 18 (IL-18). These receptors are coupled to a signaling pathway that is conserved in mammals, insects, and plants, resulting in cellular activation, thereby stimulating innate immune defenses. A variety of bacterial and fungal products have been identified that serve as TLR ligands, and more recent studies have identified the first endogenous protein ligands for TLR proteins. While TLR signaling is likely to be a key feature of innate immune responses, these proteins may also regulate homeostasis via interaction with endogenous protein ligands. PMID- 11191642 TI - Nine polymorphisms of angiotensinogen gene in the susceptibility to essential hypertension. AB - Even if the importance of angiotensinogen (AGT) gene has been known in gene targeting animals and humans genetic studies, its precise mechanism and the interaction among AGT gene variants, plasma AGT concentration and risk for hypertension remain uncertain. We examined whether AGT gene variants predispose to hypertension via an increase of plasma AGT concentration. Plasma AGT concentration was estimated from plasma angiotensin I which was cleaved by an excess amount of human renin and measured by RIA. Using 9 AGT gene variants which included new polymorphisms (G-152A and T+31C), we examined the association with hypertension and with plasma concentration by a case-control study. Haplotype analysis revealed that G-6A, T+31C and M235T polymorphisms were in absolute linkage disequilibrium and were associated with hypertension but not with plasma AGT level. On the other hand, -1074t;T235 haplotype was associated with an increase of AGT level but not with hypertension. In the haplotype analysis, only H3 haplotype frequency, which contained G-6, T+31 and M235 alleles, was significantly increased in normotensive subjects, suggesting that this haplotype is associated with a hypotensive effect. According to combined haplotype analysis of diallele and microsatellite markers, it remains a possibility that M235T, T+31C, G-6A, A-20C and G-1074T polymorphisms may play an important role in increased risk for essential hypertension. Our results suggest that the positive association between AGT polymorphism and hypertension is not simply explained by an increase of plasma AGT concentration. PMID- 11191643 TI - Liposomes modified with a synthetic Arg-Gly-Asp mimetic inhibit lung metastasis of B16BL6 melanoma cells. AB - Administration of large amounts of synthetic peptides based on the Arg-Gly-Asp (RGD) sequence has been shown to suppress tumor metastasis. To overcome the rapid degradation of peptides in the circulation, an RGD mimetic, L-arginyl-6 aminohexanoic acid (NOK), was synthesized and conjugated with phosphatidylethanolamine (PE) (NOK-PE) for liposomalization. Cell adhesion assays revealed that B16BL6 murine melanoma cells adhered to immobilized NOK-PE. This adhesion was inhibited by addition of either soluble RGDS or NOK at similar concentration in a dose-dependent manner. Administration of NOK-PE liposomes (equivalent to ca. 500 microg RGD peptides) via the tail vein completely inhibited lung colonization of B 16BL6 cells. The same dose of soluble NOK was not effective in inhibition of the tumor metastasis. In addition, injection of NOK-PE liposomes via the tail vein inhibited spontaneous lung metastasis of B16BL6 cells from the primary tumor site in the hind footpad. These results suggest that NOK, a structural mimetic of RGD, is capable of suppressing metastasis by blockade of the binding of the integrins present on tumor cells to the RGD-containing extracellular matrix. PMID- 11191644 TI - HPLC-ED measurement of endogenous catecholamines in human immune cells and hematopoietic cell lines. AB - A rapid and simple HPLC-ED method is described to identify and measure catecholamines (CTs) and their major metabolites in immune cells. Using this method, intracellular CTs were quantified in human peripheral blood mononuclear cells (PBMCs), T and B lymphocytes, monocytes and granulocytes. Immune cell subsets were separated by density gradient centrifugation and immunomagnetic cell sorting. CTs were also found in the human hematopoietic cell lines NALM-6 (pre-B) and (in smaller amounts) in Jurkat (T lymphoblastoid) and U937 (promonocytic). In cultured PBMCs, intracellular CTs were reduced by both the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine and the chromaffin granule depletant reserpine. In NALM-6 cells, both alpha-methyl-p-tyrosine and the dopamine-beta-hydroxylase inhibitor disulfiram reduced intracellular CTs, supporting the presence of active synthetic pathways in these cells. Since sympathoadrenergic mechanisms play a key role in the interactions between the immune system and the nervous system, these findings may be relevant for a better understanding of the neuro-immune network. PMID- 11191645 TI - Localization of the e-NOS enzyme in endothelial cells and odontoblasts of healthy human dental pulp. AB - Nitric oxide synthases (NOS) are important enzymes present in different cells such as endothelial cells, macrophages, etc. Recently, it has been found that nitric oxide (NO) is responsible for vasodilation, blood pressure regulation, platelet aggregation, cardiac contractility, and the mediation of immunity during bacterial infections and inflammation. However, the production and role of NO in various structures of the oral cavity have not been investigated extensively. The aim of this study was to evaluate the presence of e-NOS in healthy human odontoblasts and endothelial cells of the dental pulp. Twenty healthy human dental pulps were collected and frozen and pulp slices were obtained using a cryostat. The e-NOS enzyme was revealed by immunohistochemical analysis and the enzyme level was detected by Western blotting and mRNA expression by RT-PCR. The immunohistochemical results demonstrated, for the first time, the presence of e NOS in odontoblasts and in endothelial cells. The presence of e-NOS m-RNA was confirmed by RT-PCR and the expression of the protein by Western blotting. These results clearly show that the e-NOS enzyme is present in both odontoblasts and endothelial cells of healthy human pulp. The presence of e-NOS in the odontoblast and endothelial cells of the dental pulp may mediate local vasodilation and cell proliferation. PMID- 11191646 TI - Alterations in tumorigenicity of embryonal carcinoma cells by IGF-I triple-helix induced changes in immunogenicity and apoptosis. AB - IGF-I antisense gene therapy has been applied successfully to animal models of glioma, hepatoma and teratocarcinoma. The antisense strategy has shown that tumor cells transfected with vectors encoding IGF-I antisense RNA lose tumorigenicity, become immunogenic and are associated with tumor specific immune response involving CD8+ lymphocytes. An IGF-I triple helix approach to gene therapy for glioma was recently described. The approach we have taken is to establish parameters of change using the IGF-I triple helix strategy. PCC-3 embryonal carcinoma cells derived from murine teratocarcinoma which express IGF-I were used as a model. The cells were transfected with vector which encodes an oligoribonucleotide that forms RNA-IGF-I DNA triple-helix structure. The triple helix stops the production of IGF-I. Cells transfected in this manner underwent changes in phenotype and an increase in MHC-I and B-7 cell surface molecules. They also showed enhancement in the production of apoptotic cells (60-70%). The "triple helix" transfected cells lost the ability to induce tumor when injected subcutaneously in syngeneic 129 Sv mice. When co-transfected in vitro with expression vectors encoding both MHC-I and B-7 cDNA in antisense orientation, the "triple-helix" transfected cells were down-regulated in expression of MHC-I and B 7 and the number of apoptotic cells was significantly decreased. Injection of the doubly co-transfected cells into 129 Sv mice was associated with induction of teratocarcinoma. Comparison between antisense and triple-helix transfected cells strategies showed similar immunogenic and apoptotic changes. The findings suggest that triple-helix technology may offer a new clinical approach to treatement of tumors expressing IGF-I. PMID- 11191647 TI - The influence of sex and gonadectomy on the growth hormone and corticosterone response to hexarelin in the rat. AB - The present study is designed to investigate the role of sex and gonadal status in the growth hormone (GH) and corticosterone response to hexarelin (HEXA), a GH releasing peptide, which also causes a stimulatory action on the hypothalamic pituitary-adrenal (HPA) axis. HEXA (80 microg/Kg) was administered intracarotid to anesthetized intact or gonadectomized male (ORC) and female (OVX) middle-aged rats. The GH stimulatory response to HEXA was gender-related since the GH increase was significantly (p < 0.001) higher in intact males (area under the curve, AUC= 12560 +/- 1784 ng/ml.45 min) than in females (AUC= 4628 +/- 257 ng/ml.45 min). This sex difference does not depend on circulating gonadal steroids since it persists in ORC (AUC = 11980 +/- 1136 ng/ml.45 min) and OVX (AUC = 5539 +/- 614 ng/ml.45 min) rats. The different effects of HEXA on corticosterone secretion detected in male and female rats are probably dependent on the prevailing activity of the HPA axis. In fact, in male rats that have low basal corticosterone levels, HEXA caused an increase in corticosterone secretion, which was significantly (p< 0.05) higher in ORC than in intact rats. The increase in corticosterone secretion by HEXA both in intact and OVX females was delayed, probably due to the elevated initial corticosterone levels, which could have activated the glucocorticoid negative feedback. We suggest that gender-specific patterns in the regulation of the hypothalamus-pituitary function could be responsible for the GH and corticosterone sexually differentiated responses to HEXA. PMID- 11191648 TI - A survey of adenine and 4-aminopyrazolo[3,4-d]pyrimidine (4-APP) as inhibitors of ribosome-inactivating proteins (RIPs). AB - The inhibitory power of adenine and 4-aminopyrazolo[3,4-d]pyrimidine (4-APP) on the RNA-N-glycosidase activity catalyzed by bacterial (Shiga toxin 1) and plant (ricin, gelonin, momordin, bryodin-R, PAP-S, luffin, trichosantin, saporin 6 and barley) RIPs has been compared. The behavior of the two inhibitors is largely variable. While Shiga toxin 1 is preferentially inhibited by 4-APP, plant RIPs are either preferentially inhibited by adenine, or equally inhibited by the two compounds or, finally, only slightly more by 4-APP. Sequence variabilities involved in these different behaviors are discussed. The experimental data clearly indicate that, in spite of the same mechanism of action, RIPs differ widely in the ability to fit small ring molecules in the active cleft. While the strong inhibitory power of 4-APP on Shiga toxin 1 opens perspectives of therapeutic interventions, the ineffectiveness of the compound on ricin precludes its use as a suitable antidote in poisoning. PMID- 11191649 TI - Potentiation of DOM-induced stimulus control by non-competitive NMDA antagonists: a link between the glutamatergic and serotonergic hypotheses of schizophrenia. AB - The present investigation examined the interaction between 2,5-dimethoxy-4 methylamphetamine [DOM] and non-competitive NMDA antagonists in rats trained with DOM [0.6 mg/kg; 75 min pretreatment time] as a discriminative stimulus. Pretreatment with phencyclidine [PCP] at a dose of 3 mg/kg shifted the DOM dose response relationship to the left. When a fixed dose of DOM [0.1 mg/kg] which by itself yielded 32% DOM-appropriate responding was combined with a range of doses of PCP, dizocilpine, and ketamine, DOM-appropriate percentages increased to maxima of 73%, 84%, and 79%, respectively. When given alone, PCP, dizocilpine, and ketamine were followed by maxima of 36%, 15%, and 13%, respectively. It is concluded that the effects of DOM as a discriminative stimulus are potentiated by pretreatment with non-competitive antagonists of glutamate receptors of the NMDA subtype. These data suggest that the application of the technique of drug-induced stimulus control may prove useful in the reconciliation and integration of current hypotheses as to the etiology of psychotic disorders. PMID- 11191650 TI - Frequency-dependent blockade of T-type Ca2+ current by efonidipine in cardiomyocytes. AB - Efonidipine is a dihydropyridine Ca2+ antagonist with inhibitory effects on both L-type and T-type Ca2+ channels and potent bradycardiac activity especially in patients with high heart rate. In the present study, we examined the frequency dependence of efonidipine action on the T-type Ca2+ channel in isolated guinea pig ventricular myocytes. The potency of efonidipine to inhibit the T-type Ca2+ current was higher under higher stimulation frequencies. The IC50 values were 1.3 x 10(-8), 2.0 x 10(-6) and 6.3 x 10(-6) M under stimulation frequencies of 1, 0.2 and 0.05 Hz, respectively. The reduction of T-type Ca2+ current amplitude was not accompanied by change in the time course of current decay. Efonidipine (10 microM) inhibited T-type Ca2+ current elicited by depolarization from holding potentials ranging from -90 to -30 mV by about 30%; the voltage-dependence of steady-state inactivation was not changed by the drug. Efonidipine slowed the recovery from inactivation following an inactivating prepulse. In conclusion, efonidipine was shown to have frequency-dependent inhibitory effects on the T type Ca2+ channel, which could be explained by slow dissociation of the drug from the inactivated state of the channel. PMID- 11191651 TI - Effect of vitamin E on the degradation of hydrogen peroxide in cultured human umbilical vein endothelial cells. AB - Vitamin E reacts with radicals such as lipid peroxyl radical (LOO*) and singlet oxygen ((1)O2), and plays a role in inhibiting lipid peroxidation in cell membranes and preventing the oxidation of low-density lipoproteins (LDL). However, only a few studies have investigated the effect of vitamin E on the degradation of hydrogen peroxide (H2O2). Therefore, we examined the effect of vitamin E on glutathione redox cycle-dependent H2O2 degradation activity in human umbilical vein endothelial cells (HUVEC). Confluent HUVEC were cultured for seven days in media containing various concentrations of vitamin E (alpha-tocopherol). The level of glutathione redox cycle-dependent H2O2 degradation activity and the intracellular glutathione level were determined. HUVEC that had been cultured in the presence of higher concentrations of vitamin E had a higher level of H2O2 degradation activity and a higher intracellular content of the reduced form of glutathione (GSH). Therefore, it is suggested that the vitamin E-induced increase in H2O2 degradation activity in HUVEC results from an increase in intracellular GSH level. PMID- 11191652 TI - The diabetic foot 2000. PMID- 11191653 TI - Re: Adey et al. Reduced synthesis of muscle proteins in chronic renal failure. Am J Physiol Endocrinol Metab 278: E219-E225, 2000. PMID- 11191654 TI - Lymphangiogenesis and tumor metastasis: more questions than answers. PMID- 11191655 TI - Specific adhesion molecules bind anchoring filaments and endothelial cells in human skin initial lymphatics. AB - Anchoring filaments are a characteristic feature of initial lymphatic vessels. They connect the abluminal membrane of endothelial cells to the surrounding elastic fibers. The main molecular component of anchoring filaments is fibrillin. Initial lymphatic vessels of human skin were stained with monoclonal antibodies to fibrillin, integrins alpha 2 beta 1, alpha 3 beta 1 and alpha v beta 3, vinculin, talin, beta-actin and focal adhesion kinase (FAK). A double-labeling immunofluorescence method was used to simultaneously stain fibrillin and alpha 3 beta 1 integrin or FAK. Close contiguities between integrins and anchoring filaments were observed. These results suggest that the anchoring filaments connect the extracellular matrix and the endothelial cell cytoskeleton through the transmembrane integrin and FAK molecule. The results also demonstrate the presence of focal adhesions in the wall of initial lymphatic vessels. These connections possibly enable transmission of chemical and/or mechanical stimuli from the extracellular matrix to the endothelial cells. Here, they are transformed in cytoskeleton rearrangements and intracellular signaling events, some of which may contribute to the initial formation of lymph. PMID- 11191656 TI - An imaging evaluation of angiodysplasia syndromes. AB - Current imaging techniques such as magnetic resonance, magnetic resonance angiography, computer tomography, ultrasound, plain x-rays, and lymphangioscintigraphy have enhanced the ability to define blood and lymph vascular malformations in more precise pathophysiologic terms. Not only can these imaging modalities distinguish arterial anomalies from lymphatic and venous angiodysplasia, but they also readily differentiate edema in the epifascial as opposed to the subfascial peripheral compartments. Moreover, visceral lymphangiectasia (e.g., chylous and non-chylous reflux), bone and muscle overgrowth, agenesis, and fat deposits can also be delineated. Clinical examples are provided including an algorithm for approaching these conditions. PMID- 11191657 TI - The role of operative management of varicose veins in patients with lymphedema and/or lipedema of the legs. AB - The role of operative management of "symptomatic" varicose veins in patients with lower extremity lymphedema or lipedema is controversial. We reviewed the clinical outcome of 261 patients between 1989-1997 at the Foldiclinic with lower extremity lymphedema (68 patients), lipo-lymphedema or lympho-lipedema (103 patients) or lipedema (90 patients) who had undergone operation for varicose veins. In each group, the results were dismal as leg swelling worsened or was unchanged in greater than 90% whereas symptoms such as heaviness, fatigue, cramps (termed varicogenic symptomatology) were improved in less than 10%. These findings support that operations for varicose veins in the legs of patients with lymphedema, lipedema, or combinations of these disorders should be undertaken only if there is an absolute indication present (ascending phlebitis and/or bleeding). Otherwise, complete decongestive physiotherapy is still the best treatment approach for these groups of patients. PMID- 11191658 TI - Ignorance in AIDS KS and septicemias. PMID- 11191659 TI - Lymphoscintigraphic evaluation in patients after erysipelas. AB - Erysipelas (cellulitis/lymphangitis) is a superficial cutaneous infection spread by the lymphatic system which may result in permanent injury to the lymphatic vessels. The study evaluated the lymphatic drainage in the lower limbs of 30 patients with at least two episodes of erysipelas by means of lymphoscintigraphy. Twenty-two (73%) were female and 8 (27%) were male with ages ranging from 26 to 77 years (mean 52 years). Lymphoscintigraphy was performed by intradermal administration of 500 microCi (20 Mbq) of 99mTc antimony sulfur-colloid in two interdigital spaces of the feet. Whole body scintigraphy was performed 45 minutes after the administration of the radiopharmaceutical using a computerized gamma camera. Significant lymphatic abnormalities were found in 23 (77%) of these patients. We conclude that most patients with repeated erysipelas have significant and even permanent abnormalities in regional lymphatic drainage. Recurrent erysipelas suggests underlying primary or secondary lymphedema. PMID- 11191660 TI - Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. PMID- 11191661 TI - Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. PMID- 11191662 TI - Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. PMID- 11191663 TI - Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. PMID- 11191664 TI - Shortened zidovudine regimens to prevent mother-to-child transmission of HIV-1. PMID- 11191665 TI - Treatment of systemic mast-cell disease with cladribine. PMID- 11191666 TI - Survivors of breast cancer. PMID- 11191667 TI - Survivors of breast cancer. PMID- 11191668 TI - Transmission of histoplasmosis by organ transplantation. PMID- 11191669 TI - Aspergillus fungus balls on the mitral valve. PMID- 11191670 TI - [Spinal cord disorders and systemic diseases]. PMID- 11191671 TI - [Dehydroepiandrosterone and adrenal insufficiency]. PMID- 11191672 TI - [Acute myelitis and Behcet's disease: three case reports]. AB - INTRODUCTION: Neurological manifestations in Behcet's disease usually consist of meningoencephalitis and cerebral thrombophlebitis. Myelitis is rare, especially when it is the only neurological manifestation. EXEGESIS: The authors report three cases of acute myelitis complicating Behcet's disease demonstrated by magnetic resonance imaging. In two cases, Behcet's disease was revealed by myelitis. The three cases were transverse myelitis, two of which were juvenile Behcet's disease and two were meningomyelitis. CONCLUSION: Magnetic resonance imaging can help guide diagnosis of myelitis in Behcet's disease. It can also be useful to assess the results of the treatment. Clinical symptoms of Behcet's disease must be searched for in the case of myelitis, especially for patients from Mediterranean countries. PMID- 11191673 TI - [Drug-induced hypersensitivity syndrome in internal medicine: diagnostic and therapeutic traps. Eight observations]. AB - PURPOSE: Drug-induced hypersensitivity syndrome (DIHS) is an acute and severe drug reaction. Manifestations include severe skin lesions, fever, nodal enlargement, blood eosinophilia and multisystemic involvement. The severe systemic manifestations of DIHS are responsible for a 10% mortality rate. The pertinence of corticosteroid therapy is discussed. METHODS: The authors report eight retrospective cases of DIHS obtained from the PMSI (Programme de Medicalisatiopn des Systemes d'Information) between November 1991 and November 1998. RESULTS: The series consisted of five male and three female patients (mean age: 52.6 years; range: 23-83 years). The interval between the introduction of the drug and the onset of the reaction varied from two to eight weeks. Due to severe systemic manifestations, three patients were given corticosteroid therapy. Healing of skin and systemic disorders resolved with a mean delay of 4.4 weeks (range: 1 to 56 weeks). CONCLUSION: DIHS can be a diagnostic trap, as there are no diagnostic criteria for DIHS. Only the association of multiple arguments such as the time to the occurrence of symptoms, clinical similarity to many infectious illnesses, hypereosinophilia, atypical lymphocytosis, etc. may help guide diagnosis. DIHS can also be a therapeutic trap, as prompt withdrawal of the offending drug is essential to minimize morbidity. Although still controversial in the literature, the pertinence of corticosteroid therapy may be discussed in case of severe systemic effects. Patch testing can be a valuable tool to determine the responsibility of a drug; however it proves to be useful only when positive. PMID- 11191674 TI - [Monoclonal gammopathies of undetermined significance]. AB - INTRODUCTION: Monoclonal gammopathy of undetermined significance is an asymptomatic disorder associated with serum monoclonal immunoglobulin spike. Its incidence is about 1% in patients of 50 years of age, and rapidly increases in elderly patients. CURRENT KNOWLEDGE AND KEY POINTS: Within the 20 years following diagnosis, about 25% of patients will evolve towards either multiple myeloma (for patients with IgG or IgA) or malignant lymphoproliferative disorder (for patients with IgM). Definition, circumstances associated with a transient monoclonal spike, and currently available parameters used for differential diagnosis with either multiple myeloma or malignant lymphoproliferative disorder are successively discussed. One part of the most usual biological parameters is of prognostic value, and is reviewed in more detail. Recent data concerning immunophenotype, cytogenetics and molecular biology of plasma cells reinforce the link between the asymptomatic condition and multiple myeloma. In monoclonal gammopathy of undetermined significance, some plasma cells resemble normal or reactive plasma cells, whereas others mimic those found in multiple myeloma. FUTURE PROSPECTS AND PROJECTS: The most recent biological data are also discussed in order to evaluate whether some would help to discriminate those patients who will remain asymptomatic lifelong from those who will evolve towards multiple myeloma. PMID- 11191675 TI - [Recent progress in the diagnosis, prognostic evaluation and treatment of pheochromocytomas]. AB - INTRODUCTION: Pheochromocytoma is a catecholamine-secreting neoplasm of chromaffin tissue. It is a rare disease. Biochemical tests should be performed only in patients at high risk of pheochromocytoma, and an imaging procedure only in those with positive biochemical tests. CURRENT KNOWLEDGE AND KEY POINTS: The most specific and sensitive diagnostic test for the disease is the determination of plasma or urinary metanephrines. The tumor can be located by computerized tomography, magnetic resonance imaging, and specific scintigraphy. Ten to 20% of pheochromocytomas result from hereditary diseases, including multiple endocrine neoplasia type 2, von Hippel Lindau disease, and neurofibromatosis 1. Familial cases are diagnosed earlier, and are more frequently bilateral and recurring than sporadic cases. About 10% of the cases are malignant either at first operation or during follow-up, malignancy being diagnosed by the presence of lymph node, visceral or bone metastases. The probability of a recurrence is positively correlated with the urinary excretion of metanephrines and tumor size. Recurrences are more frequent in cases with ectopic tumors and in those with a low plasma epinephrine to total catecholamine ratio. Patients, especially those with familial tumors or low epinephrine secretion, should be followed-up indefinitely. FUTURE PROSPECTS AND PROJECTS: Treatment for malignant recurrences includes surgery, therapeutic embolization, chemotherapy, and the application of therapeutic doses of metaiodobenzylguanidine. Metyrosine, phenoxybenzamine, or somatostatin analogs may help to control blood pressure and to alleviate symptoms in patients with malignant pheochromocytoma; however such a treatment has no antiproliferative effect. PMID- 11191676 TI - [Fabry disease. Clinical and genetic aspects. Therapeutic perspectives]. AB - INTRODUCTION: This review presents the clinical and genetic aspects of Fabry disease, along with recent advances in research. CURRENT KNOWLEDGE AND KEY POINTS: Fabry disease is an X-linked inborn error of metabolism due to a deficient activity of the lysosomal enzyme alpha-galactosidase A. The enzymatic defect leads to the systemic accumulation of neutral glycosphingolipids in plasma and tissues. Clinical manifestations in affected hemizygous males are primarily due to progressive disease of small vessels, including angiokeratoma, autonomic dysfunction, and lifelong debilitating pain. Renal failure and vasculopathy of the heart and brain lead to early demise in adulthood. Demonstration of alpha galactosidase A deficiency in leukocytes or plasma is the definitive method for the diagnosis of affected hemizygous males. Most female carriers are clinically symptomatic, they may present isolated acroparesthesia, cardiac symptoms, or the characteristic benign corneal dystrophy. Due to random X-chromosomal inactivation, enzymatic detection of carriers is often inconclusive. A reliable molecular test for detection of heterozygosity is therefore highly desirable for accurate genetic counselling. The GLA gene has been mapped to chromosome Xq22, and cloned. Several studies have shown the molecular heterogeneity of the disease. Currently, no standard treatment exists for Fabry disease. Symptomatic treatment is provided as appropriate. In addition, renal transplantation or dialysis is available for patients experiencing end-stage renal failure. FUTURE PROSPECTS AND PROJECTS: The ability to produce high doses of recombinant alpha galactosidase A in vitro has opened the way to preclinical studies in the mouse model and led to the development of the first clinical trials with enzyme replacement therapy in patients with Fabry disease. PMID- 11191677 TI - ["Multiple sclerosis plus": leukoencephalopathies at the frontiers of internal medicine]. AB - INTRODUCTION: Multiple sclerosis (MS) is an inflammatory, demyelinating and probably autoimmune disease affecting the white matter of the central nervous system (CNS). Due to the absence of specific clinical and laboratory markers, diagnosis remains difficult. CURRENT KNOWLEDGE AND KEY POINTS: In particular, no clinical or paraclinical investigation is satisfactory to distinguish definite MS from other autoimmune or inflammatory diseases, especially when they predominantly affect the CNS. Moreover, previous studies have reported that patients with definite MS could present clinical systemic signs suggestive of other inflammatory or autoimmune diseases, and that MS could be associated with other autoimmune diseases. On the other hand, the presence of biological autoimmune abnormalities, including antinuclear antibodies and antiphospholipid antibodies, has been observed, with a high frequency in patients with MS in comparison to control populations. These clinical and laboratory features could therefore represent a new nosological entity characterized by a systemic immune dysregulation more extensive than the CSN target, or a distinct subgroup of MS patients with a classical course of the disease. Because of the impact of the new therapeutic approach to MS, an important issue concerning this aspect that should be addressed is the use of immunomodulatory therapy, especially with interferon beta. It appears necessary to consider these abnormalities before treating MS patients with preventive therapy, in particular in the perspective of new strategies, such as treatment at an early stage of the disease or combination therapies. PMID- 11191678 TI - [Myelopathy revealing lupus. Two cases and review of the literature]. AB - INTRODUCTION: Myelopathy is a rare manifestation of systemic lupus erythematosus, occurring most often during the course of the disease. EXEGESIS: We report two cases of women with myelopathy as the first manifestation of systemic lupus erythematosus; both had an unusual course. We review the literature for previously reported cases. CONCLUSION: The clinical presentation of myelitis is heterogeneous. Usually, neurologic deficits evolve within a few hours (typically acute transverse myelitis) and outcome is usually poor. However, chronic or recurrent transverse myelitis has also been reported, including relapsing myelitis that resolved spontaneously. Myelopathy can be the first manifestation of the disease and this might be more common than initially thought. Magnetic resonance imaging (MRI) findings depend on the timing of the examination and the stage of the disease; the MRI may therefore be normal. An association with optic neuritis is frequently reported in the literature and differential diagnosis with multiple sclerosis may be difficult. Overlapping features between both diseases have been termed "lupoid sclerosis" and are actually classified as demyelinating syndromes associated with lupus. Myelopathy does not appear to be consistently associated with antiphospholipid antibodies, as has been previously suggested. The best treatment protocol has not been determined; however, in recent years, pulses of methylprednisolone and cyclophosphamide have gained acceptance by most authors. PMID- 11191679 TI - [Laryngeal amyloidosis: a rare cause of hoarseness]. AB - INTRODUCTION: The larynx is a rare site of deposition for amyloidosis. Diagnosis may be delayed and evoked in patients with prolonged hoarseness. We have reported two cases of laryngeal amyloidosis. EXEGESIS: One man and one woman suffered from hoarseness during one and three years, respectively. Laryngoscopic examination showed diffuse infiltration of the larynx. Amyloidosis was confirmed by the characteristic Congo-red staining of laryngeal biopsies. The search for other localizations of amyloidosis was negative. No monoclonal plasma cell proliferation was detected. Both patients received endoscopic CO2 laser excision. In one case, chemotherapy was initially associated due to dystrophic plasma cells in bone marrow aspiration and then withdrawn because of clinical failure. With a 6-month follow-up, hoarseness remained stable. CONCLUSION: Laryngeal amyloidosis is an essentially localized disease revealed by hoarseness. Treatment is endoscopic by laser excision. In nearly half of the cases in the literature, it had to be repeated due to localized recurrent lesions. Long-term prognosis of localized laryngeal amyloidosis is better than systemic AL amyloidosis. PMID- 11191680 TI - [A swelling of the sternum during respiration]. PMID- 11191681 TI - [Capillary leak syndrome in the course of Gaucher disease: the result of monoclonal gammopathy?]. PMID- 11191682 TI - [Hyperthyroidism: a cause of serum ferritin elevation]. PMID- 11191683 TI - [Uveitis after the age of 60]. PMID- 11191684 TI - [Adult-onset Still's disease, a rare cause of acute respiratory distress]. PMID- 11191685 TI - [Dihydropyrimidine dehydrogenase deficiency and 5-fluorouracil toxicity]. PMID- 11191686 TI - Risperidone-associated weight gain in children and adolescents: a retrospective chart review. AB - OBJECTIVE: Risperidone use has been associated with substantial weight gain in children and adolescents. Reports available to date have consisted of small case series evaluated without standardized indices of developmentally normative weight increase. The purpose of this study was to evaluate age- and gender-adjusted weight changes linked to risperidone use in a juvenile psychiatric inpatient population. METHOD: Thirty-seven child and adolescent inpatients treated with risperidone for 6 consecutive months were compared to a group of 33 psychiatric inpatients with no atypical neuroleptic exposure. Weight, height, and body mass index (BMI) were recorded on at least a monthly basis, and Tanner staging was completed on admission. Percent change from baseline weight, changes in standardized z scores of weight for age and gender, and proportion of subjects experiencing a < or = 7% weight increase from baseline were compared among groups. RESULTS: Subjects in both groups were comparable at baseline except for gender distribution (more males were in the risperidone group, p < 0.05). Risperidone-treated children and adolescents experienced significant weight gain between baseline and endpoint (paired t test, p < 0.001) that was first evident within 2 months of starting treatment, progressed steadily at an average rate of 1.2 kg/month, and did not reach a clear plateau during 6 months of observation. Significant increases in standardized weight were noted at 3 and 6 months for risperidone-treated subjects. Risperidone use conferred a substantial risk of gaining over 7% from baseline weight (odds ratio = 3.5, 95% confidence interval = 1.8-6.6, p < 0.001). CONCLUSIONS: Six-month exposure to risperidone was associated with clinically significant weight gain in 78% of treated children and adolescents (as opposed to 24% of those in the comparison group, p < 0.001). Risperidone dosage, concomitant medication use, and other demographic characteristics such as age, pubertal status, gender, and baseline weight and BMI were not associated with an increased risk of morbid weight gain. Standardized z scores offer advantages for the assessment of weight change among developing children and adolescents. PMID- 11191687 TI - Cognitive side effects of electroconvulsive therapy in adolescents. AB - OBJECTIVE: The primary aim of this study was to determine the presence of cognitive impairments among adolescents treated with electroconvulsive therapy (ECT) and whether these deficits would persist several months following the treatment. METHODS: Retrospective data resulting from standard clinical care of a convenience sample with naturalistic follow-up were used. Subjects were 16 adolescents (13 females, 3 males; mean age = 15.9 +/- 1.6 years) hospitalized with a mood disorder (unipolar depression = 14, bipolar depression = 2). Cognitive tests administered prior to ECT were compared with results at 7.0 +/- 10.3 days following the last treatment and with a second testing at 8.5 +/- 4.9 months after the last treatment. RESULTS: Comparison of pre-ECT and the first post-ECT testing administered during the first 10 days of the treatment yielded significant impairments of concentration and attention, verbal- and visual delayed recall, and verbal fluency. A complete recovery of these functions was noted at the second post-ECT testing. There was no deficit in the ability to problem solve during the initial or the subsequent testing. CONCLUSION: Cognitive parameters found to be impaired during the first few days of ECT recovered over several months following the treatment. Therefore, there was no evidence of long term damage to concentration, attention, verbal and visual memory, or verbal fluency. There were no impairments of motor strength and executive processing, even during the early (within 7-10 days) post-ECT period. These results should be regarded as preliminary, awaiting confirmation with larger samples. PMID- 11191688 TI - Effects of subchronic methylphenidate hydrochloride administration on the locomotor and exploratory behavior of prepubertal mice. AB - The increasing use of methylphenidate hydrochloride (MPH) in children led us to examine the effects of MPH administration in developing mice. Male CD-1 mice were administered MPH (40 mg/kg, subcutaneously) or saline daily from postnatal days 26-32. The mice were then tested from postnatal days 33-37 for locomotion and exploration in the open field, anxiety in the elevated plus maze, and learning in the Morris water maze. The results indicate that MPH-pretreated mice were more exploratory and less fearful in the open field, entering more center squares than saline controls. MPH-pretreated mice also exhibited less anxiety, spending more time in the open arm and exhibiting more head dips in the elevated plus maze than controls. There was no significant difference between MPH and saline-treated mice in the time taken to find the visible or hidden platform in the water maze task. The results indicate that treatment with MPH has significant effects on later behavior, reducing fear and anxiety, and increasing exploration, but no effect on performance in a spatial learning task. PMID- 11191689 TI - Antidepressant treatment and neural plasticity. AB - The use of psychopharmacologic agents in children is complicated by several factors. One important neurobiologic consideration is the relationship of the effect of the medication to ongoing brain development. Although available data are inadequate to address this issue directly, a review of ancillary data suggests that there are theoretical reasons to exercise prudence in prescribing psychopharmacologic agents. For example, the effects of serotonin on neuronal plasticity suggest that agents that can alter serotonergic function may alter neuronal wiring. Although this can occur in any brain, it may be of particular importance in a developing nervous system. The consequences of these induced changes are not clear. Animal studies on the effect of long-term antidepressant administration in immature pups may begin to answer some of the clinical concerns of these observations. PMID- 11191690 TI - The effect of fluvoxamine and behavior therapy on children and adolescents with obsessive-compulsive disorder. AB - OBJECTIVE: The efficacy of medications, consisting of serotonin partial and specific reuptake blockers, and behavior therapy, consisting of exposure and response prevention in addition to social skills training, cognitive therapy, and habit reversal, in the treatment of obsessive-compulsive disorder are well documented. The purpose of the study was to explore if adding behavior therapy to medication would enhance treatment efficacy. METHODS: Ten children/adolescents who had not previously responded to behavior therapy were randomly assigned to two groups: fluvoxamine alone or fluvoxamine with behavior therapy. All 10 patients received fluvoxamine for 10 weeks-five continued solely on fluvoxamine for one year and five engaged in behavior therapy for 20 sessions along with fluvoxamine and then continued solely on medication until the end of the year. RESULTS: Eight of 10 patients improved significantly on fluvoxamine at week 10 on the primary outcome variable, the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). According to the other measurements-National Institute of Mental Health-Global Obses-sive-Compulsive Scale, Clinical Global Impression-Improvement (assessing level of im-provement from week to week), and Clinical Global Impression-Severity of Illness Scale (as-sessing how ill the patient is from week to week)-improvement was not as evident. According to the CY-BOCS, those who received a combination of fluvoxamine and exposure with response prevention showed significantly more improvement than those who only took medication. At two year follow-up, all patients continued to improve, with those in the combined approach improving more than those in the medication-alone group. CONCLUSIONS: Future studies should determine the specific effect of each treatment group, combined and singularly. Reasons for discrepancy in improvement ratings as noted by the different instruments are discussed. The addition of behavior therapy to fluvoxamine seems to enhance treatment efficacy, according to the CY-BOCS. PMID- 11191691 TI - Combined treatment with haloperidol and trazodone in patients with tic disorders. AB - The combination of haloperidol and trazodone was evaluated in an open-label trial in 10 patients with chronic tic and Tourette's syndrome. We found a mean reduction of symptoms of 58.9% on the Yale Global Tic Severity Scale, with a statistically significant difference (p < 0.001) between the baseline and endpoint treatment conditions. This approach significantly reduces clinical symptoms, with the advantage of a lower dose of haloperidol than usual, with no side effects reported by the patients. PMID- 11191692 TI - Efficacy of modafinil compared to dextroamphetamine for the treatment of attention deficit hyperactivity disorder in adults. AB - Our objective was to compare the efficacy of the new wake-promoting drug modafinil to that of dextroamphetamine for the treatment of attention deficit hyperactivity disorder (ADHD) in adults. Twenty-two adults who met DSM-IV criteria for ADHD participated in a randomized, double-blind, placebo-controlled, three-phase crossover study comparing placebo, modafinil, and dextroamphetamine for the treatment of ADHD. The twice-daily study medications were titrated to doses of optimum efficacy over 4-7 days and then held constant during the rest of each 2-week treatment phase. Measures of improvement included the DSM-IV ADHD Behavior Checklist for Adults, the Controlled Oral Word Association Test (COWAT, using the letters C, F, and L version), Stroop, and Digit Span (Wechsler Adult Intelligence Scale version). For the 21 (96%) completers, the mean (+/- SD) optimum doses of modafinil and dextroamphetamine were 206.8 mg/day +/- 84.9 and 21.8 mg/day +/- 8.9, respectively. Scores on the DSM-IV ADHD Checklist (p < 0.001) were significantly improved over the placebo condition following treatment with both active medications. Performance on the COWAT (p < 0.05) reached trend levels of significance. Both medications were generally well tolerated. This preliminary study suggests that modafinil may be a viable alternative to conventional stimulants for the treatment of adults with ADHD. PMID- 11191693 TI - Sudden death of a child treated with imipramine. Case study. AB - Since 1990, there have been seven reported cases of sudden death in children treated with tricyclic antidepressants. This case study describes the sudden death of an additional child (8 years 9 months old, 29 kg in weight) treated with a tricyclic antidepressant, imipramine (100 mg orally, twice daily), and dextroamphetamine (10 mg orally every morning). Prior to death, there were signs of possible cardiovascular abnormalities after treatment was begun with imipramine. The report adds to the concern over the use of tricyclics in children. PMID- 11191694 TI - Case study. Risperidone-Induced neuroleptic malignant syndrome in an adolescent. AB - Neuroleptic malignant syndrome (NMS) is a potentially fatal complication of neuroleptic therapy, characterized by fever, rigidity, mental status changes, and autonomic instability. Although NMS was previously associated with the use of high-potency neuroleptics, cases have begun to emerge with atypical neuroleptics. This article presents a risperidone-induced case in the youngest patient to date, raising issues concerning our perceptions, the safety of newer neuroleptics, and treatment of NMS. PMID- 11191695 TI - Change management of shared and local versions of health-care terminologies. AB - Local sites that adopt a shared health-care terminology for computer-based systems have local needs that prompt the local-terminology maintainers to make changes to the local version of the shared terminology. If the local site is motivated to conform to the shared terminology, then the burden lies with the local site to manage its own changes and to incorporate the changes of the shared version at periodic intervals. We call this process synchronization. We survey current approaches that address problems of sharing and local modification, and we present the CONCORDIA model, which supports carefully controlled divergence of a local version from a shared terminology. CONCORDIA provides the underlying design and methodology for the implementation of a synchronization-support tool. PMID- 11191696 TI - An architecture for a brain-image database. AB - The widespread availability of methods for noninvasive assessment of brain structure has enabled researchers to investigate neuroimaging correlates of normal aging, cerebrovascular disease, and other processes; we designate such studies as image-based clinical trials (IBCTs). We propose an architecture for a brain-image database, which integrates image processing and statistical operators, and thus supports the implementation and analysis of IBCTs. The implementation of this architecture is described and results from the analysis of image and clinical data from two IBCTs are presented. We expect that systems such as this will play a central role in the management and analysis of complex research data sets. PMID- 11191697 TI - Web-enabled medical databases: a threat to security? AB - An increasing number of clinical databases are being adapted to allow access through Internet protocols, particularly Hypertext Transfer Protocol (HTTP). The World Wide Web (WWW) provides a user-friendly, standardized, broadly distributed database interface; at the same time, it may also present a threat to the security and confidentiality of patient data. However, there is little empirical evidence concerning such threats. Using publicly available records we estimate the additional risk of security violations due to web-enabling a database. The evidence, though limited, suggests that the additional risk may be small relative to more traditional security threats. PMID- 11191698 TI - A data mining system for infection control surveillance. AB - Nosocomial infections and antimicrobial resistance are problems of enormous magnitude that impact the morbidity and mortality of hospitalized patients as well as their cost of care. The Data Mining Surveillance System (DMSS) uses novel data mining techniques to discover unsuspected, useful patterns of nosocomial infections and antimicrobial resistance from the analysis of hospital laboratory data. This report details a mature version of DMSS as well as an experiment in which DMSS was used to analyze all inpatient culture data, collected over 15 months at the University of Alabama at Birmingham Hospital. PMID- 11191699 TI - Validation of ICTERUS, a knowledge-based expert system for Jaundice diagnosis. AB - The study aimed to describe an example of the assessment and validation of knowledge-based clinical expert systems. The paper focuses on ICTERUS, an expert system for jaundice diagnosis. It describes system design, the methodology applied for upgrading and validating the program, and the most important outcomes of the validation procedure. The clinical validation of the system on a very large European database (Euricterus Project) shows that diagnostic conclusions are reliable in about 70% of eligible cases. This figure appears acceptable for a system which provides decision support only on the basis of clinical data, assuming that the final decision is achieved under user responsibility. Expected biases, limitations and inconsistencies in the practical application of the system are discussed. PMID- 11191700 TI - Data processing at the anesthesia workstation: from data entry to data presentation. AB - Main requirements for an Anesthesia Information Management System (AIMS) are the supply of additional information for the anesthesiologist at his workstation and complete documentation of the anesthetic procedure. With the implementation of an AIMS (NarkoData) and effective user support, the quality of documentation and the information flow at the anesthesia workstation could be increased. Today, more than 20,000 anesthesia procedures are annually recorded with the AIMS at 112 decentralized workstations. The network for data entry and the presentation and evaluation of data, statistics and results directly available at the clinical workstation was made operational. PMID- 11191701 TI - Evaluation of three Swedish ICD-10 primary care versions: reliability and ease of use in diagnostic coding. AB - If computer-stored information is to be useful for purposes other than patient care, reliability of the data is of utmost importance. In primary healthcare settings, however, it has been found to be poor. This paper presents a study on the influence of coding tools on reliability and user acceptance. Six general practitioners coded 152 medical problems each by means of three versions of ICD 10, one with a compositional structure. At code level the reliability was poor and was almost identical when the three versions were compared. At aggregated level the reliability was good and somewhat better in the compositional structure. Ideas for improved user acceptance arose, and the study explored the need for several different tools to retrieve diagnostic codes. PMID- 11191702 TI - Computer simulation of hemodynamic parameter changes by mechanical ventilation and biventricular circulatory support. AB - When a Bi-Ventricular Assist Device (BVAD) is used in conjunction with mechanical ventilation (MV) of the lungs with positive intrathoracic pressure (Pt), the latter influences hemodynamics. The aim of our study was to assess the simultaneous influence of BVAD and MV on hemodynamics. We assumed ventricular pathological conditions as reduced elastances and increased rest volumes. Peripheral systemic arterial resistance was assumed to have different values. Data were obtained by computer simulation. Trends in main hemodynamic variables were compared with clinical data from literature. Simulation showed that systemic venous, pulmonary arterial and left atrial pressures are very sensitive to Pt (-2 to 5 mmHg). PMID- 11191703 TI - Discrete event simulation in the health policy and management program. AB - Students in Health Policy and Management at the Faculty of Health Sciences of Maastricht University must learn to analyze and design workflow processes in health care. To attain this, a discrete event simulation training, using MedModel is used. This paper describes the training in two consecutive years. In both years the training was evaluated systematically. The evaluation results demonstrate that the simulation training increased the students' knowledge about analyzing and designing workflow processes in healthcare. Students considered the training as a very important part of their program. PMID- 11191704 TI - Disaster drills and continuous medical education using satellite-based Internet. AB - We designed and evaluated a satellite-based Internet system for use in medical applications. Many experimental telemedicine projects use satellites, but we combined digital satellite communication with an ordinary telephone network to realize an economical countrywide network for emergency medicine and continuous medical education. The system appears to be a useful and practical technology for daily clinical activities. PMID- 11191705 TI - Realization of security concepts for DICOM-based distributed medical services. AB - Exploiting distributed hard- and software resources for telemedicine requires a fast, secure, and platform-independent data exchange. Standards without inherent security mechanisms such as DICOM may ease non-authorized data access. Therefore, exemplary telemedical data streams were analyzed within the Berlin metropolitan area network using specialized magnetic resonance imaging techniques and distributed resources for data postprocessing. For secure DICOM communication both the Secure Socket Layer Protocol and a DICOM-conform partial encryption of patient-relevant data were implemented. Partial encryption exhibited the highest transfer rate and enabled a secure long-term storage. Different data streams between secured and unsecured networks were realized using partial encryption. PMID- 11191706 TI - High speed digital circuits for medical communication; the MINCS-UH project. AB - In Japan, a high speed, bidirectional digital satellite communication system called Medical Information Network by Communications Satellite for University Hospitals is currently available in 30 national universities, and many programs, including clinical conferences, lectures and tutorials, have been broadcasted. Its characteristics are: (1) a state-of-the-art digital high-definition television system, (2) excellent security protection using digital encryption (3) bidirectional communications using two satellite circuits simultaneously, and (4) easy operability. High-quality motion images, and security protection mechanisms are essential for use in clinical medicine. PMID- 11191707 TI - Canine cognition, aging and neuropathology. Introduction. PMID- 11191708 TI - The canine as a model of human cognitive aging: recent developments. AB - 1. Aged dogs display many of the cognitive impairments associated with aging and dementia. 2. Aged dogs, like humans, display a wide range of individual variability in cognitive functioning (i.e., different cognitive functions decline at different rates in aged dogs). 3. Different categories of aged canines can be identified on the basis of neuropsychological test performance, and these categories can be used to model different subgroups of aged humans (i.e., dementia, mild cognitive impairment and successful aging). 4. Additional research is required to further validate the dog as a model of human cognitive aging and dementia. PMID- 11191709 TI - Development of a protocol for studying object recognition memory in the dog. AB - 1. Dogs had considerable difficulty learning a delayed-non-matching-to sample task at a short delay (approximately 5 seconds) for an extended period (900 trials). Only 3 of 19 dogs met the learning criterion. 2. Acquisition on the DNMS task was markedly improved when a pause was introduced on presentation of the stimulus objects, when the objects were approximately 30 cm from the dog; eleven of 16 dogs learned the task within 600 trials. 3. Dogs learned the task more rapidly at 20 and 30 second delays than at 10-second delays. This indicates a transfer of learning. 4. Dogs that did learn the task were able to perform at accuracy greater than 85% at delays of 150 and 200 seconds. At a 5-minute delay, performance was at 75%. 5. When the animals were switched to a repeated object paradigm, accuracy markedly declined. 6. The improved performance produced by introduction of the pause is attributable to: (1) presenting the object at a distance longer than the dogs' near point, and (2) allowing increased processing time. PMID- 11191710 TI - Adrafinil: effects on behavior and cognition in aged canines. AB - 1. Adrafmil is a novel vigilance promoting agent developed in France by Louis Lafon Laboratories. 2. Adrafinil causes increased locomotion without producing stereotypical activity in canines tested in an open field. 3. The effectiveness of a single treatment is long-lasting, and the effectiveness persists over repeated treatments. 4. Acquisition of a size discrimination problem is enhanced by adrafinil. This may be linked to performance motivation. 5. Adrafinil causes a long-lasting increase in high frequency electroencephalographic activity recorded from cortical electrodes. 6. These results indicate that adrafinil is novel behavioral stimulant with cognitive enhancing potential. The underlying mechanisms of action are still unknown. PMID- 11191711 TI - Natural animal models of human psychiatric conditions: assessment of mechanism and validity. AB - 1. The classic animal models for human psychiatric conditions involves rodents. As prey species, their normal behaviors of avoidance would be considered pathological in humans and dogs. Hence, such models may not be homologous for similar behaviors found in psychiatric pathology in humans. 2. Dogs exhibit pathological behavioral conditions that may be equivalent to certain human psychiatric conditions. These canine conditions appear spontaneously or endogenously in the absence of genetic or neurochemcial manipulation, and as such, may be homologous to the human condition. 3. If canine conditions approach homology with human conditions they should have excellent face, predictive, and construct validity. 4. The canine conditions of separation anxiety, obsessive compulsive disorder, cognitive dysfunction, dominance aggression, and panic disorder have good to excellent validity at all explored levels for human generalized anxiety disorder, obsessive-compulsive disorder, Alzheimer's disease, impulse control disorders, and panic disorder. 5. Natural canine models can aid our understanding of human psychiatric conditions. PMID- 11191712 TI - Initiation and propagation of molecular cascades in human brain aging: insight from the canine model to promote successful aging. AB - 1. Normal aging is thought to proceed through two stages: initiation and propagation. Each of these phases is associated with different neuroanatomical events, vulnerabilities to injury and responsiveness to interventions. 2. The role of beta-amyloid (Abeta) in neuron dysfunction in the initiation stage may be mediated through alterations in signal transduction pathways involving cyclic AMP response element binding protein (CREB). CREB phosphorylation is associated with the expression of brain derived neurotrophic factor (BDNF), which promotes neuron health and survival. In primary neuronal cultures, Abeta decreases the phosphorylation of CREB, which results in up to a 31% decrease in BDNF levels. 3. In vivo studies also support a role for Abeta in neuron dysfunction since soluble Abeta levels correlate with the loss of synapses in brains of non-demented humans with high pathology. 4. The authors hypothesize that interventions during the initiation stage, when neuron dysfunction, but not overt pathology, is present, have the most promise to promote successful aging. The dog can serve as a useful model for interventions during the initiation stage since dogs develop neuropathology that closely resembles that observed in high pathology human brains. PMID- 11191713 TI - DNA damage and apoptosis in the aged canine brain: relationship to Abeta deposition in the absence of neuritic pathology. AB - 1. In addition to beta-amyloid (Abeta) deposition and cytoskeletal neuropathology, both the Alzheimer's disease (AD) and Down's syndrome (DS) human brain exhibit marked evidence of DNA damage, however, it is difficult to separate events that occur in conjunction with neurofibrillary pathology versus Abeta pathology in these systems. 2. In contrast, the aged canine brain exhibits the accumulation of Abeta into diffuse deposits similar to those found in early AD and DS in the absence of neurofibrillary pathology. Furthermore, Abeta deposition in canine brain is correlated with cognitive deficits. 3. In order to test the hypothesis that TUNEL labeling for DNA damage in AD is not simply a consequence of agonal artifacts, postmortem artifacts, or neurofibrillary pathology, and may be directly related to Abeta deposition, we examined Abeta immunoreactivity, PHF 1 immunoreactivity, and TUNEL labeling in this animal model. 4. These experiments reveal a relationship between the amount of DNA damage detected by TUNEL labeling and levels of Abeta deposition. Further, in animals with no TUNEL labeling, we detected no Abeta immunoreactivity. 5. These data support the hypothesis that TUNEL labeling in AD ans DS is not a consequence of agonal artifact, postmortem artifact, or tau pathology, and may be directly related to Abeta deposition and perhaps AD pathogenesis. PMID- 11191714 TI - Ultrastructural analyses of beta-amyloid in the aged dog brain: neuronal beta amyloid is localized to the plasma membrane. AB - 1. An electron microscopic study was undertaken to study beta-amyloid (Abeta) deposition and neuropathology in aged dogs. 2. A positive correlation between Abeta deposits and neuropathology was found in some dogs. Massive Abeta deposition was correlated to advanced lesions. 3. By use of immunocytochemistry Abeta fibers were identified within plaques, around vessels and in association with cell membranes. PMID- 11191715 TI - Canine models for human genetic neurodegenerative diseases. AB - 1. Canine models of human neurodegenerative disorders are uncommon. However, the similarity between canines and humans in body sizes and physiology provides an exceptional opportunity to use these models to study human diseases. 2. The authors will present a review on the neurological deficits that have been observed in canine models of genetic neurodegenerative diseases, and summarize the current gene therapy treatments being developed for some of these conditions. PMID- 11191716 TI - Organization of connections underlying the processing of auditory information in the dog. AB - 1. The canine temporal cortex includes the ectosylvian, composite posterior and sylvian gyri. 2. The distinctive features of the canine temporal cortex include the ectosylvian sulcus closed in its dorsal side and the substantial development of neocortex located within the posterior composite gyrus. 3. Thalamofugal connections from particular nuclei of the medial geniculate body, posterior thalamus and lateromedial-suprageniculate complex project to specific areas of the canine temporal cortex and are arranged as dominant and non-dominant projections. 4. Local intracortical connections distinguish the ectosylvian and posterior composite areas as unimodal auditory cortex. Long distant connections and polymodal convergence indicate that the composite ectosylvian area of the anterior ectosylvian gyrus and the anterodorsal sylvian areas are higher order association cortex. 5. Analysis of both thalamo-cortical and intracortical connections indicate that auditory processing in the cortex occurs in successive, hierarchically organized stages and in two main, anterior and ventral pathways. PMID- 11191717 TI - Cognitive functions of the temporal lobe in the dog: a review. AB - 1 The current paper reviews the role of temporal lobe structures in learning and different kinds of memory, with an emphasis on behavioral tasks that re auditory stimuli. 2 The effects of lesions to structures in the temporal lobe were examined in separate groups of dogs, which were trained on an auditory spatial delayed response, or in a trial-unique auditory delayed match to sample recognition task. 3 Spatial memory was impaired after bilateral hippocampal lesions. On the other hand, neither an anterior temporal lesion or rhinal cortical injury nor combined lesion to the hippocampus and the anterior temporal lobe, affected postoperative retraining and performance of the spatial task. 4 Auditory recognition memory task was not impaired after a hippocampal and/or rhinal cortex lesion. However, postoperative retraining of the task was impaired after a lesion to auditory association areas. 5 These results confirm the role of the hippocampus in spatial memory in the dog. On the other hand, the organization of auditory recognition functions within the temporal lobe appears to be different from those described for visual recognition functions. PMID- 11191719 TI - Suppressive effect of sarpogrelate hydrochloride on respiratory failure and right ventricular failure with pulmonary hypertension in patients with systemic sclerosis. AB - We evaluated the effect of 12 months of 300-mg oral sarpogrelate hydrochloride (SH) once daily on the symptoms of Raynaud's phenomenon, respiratory failure and cardiac function in seven patients with systemic sclerosis. Arterial blood gases, pulmonary function, mean pulmonary arterial pressure, left ventricular ejection fraction (LVEF), right ventricular ejection fraction (RVEF), white blood cell count, C-reactive protein and the plasma concentrations of fibrinopeptide A, beta thromboglobulin, platelet factor 4 and thrombomodulin were evaluated before and 2 and 12 months after SH administration. After 2 and 12 months of SH administration, a significant decrease was found in the frequency and duration of Raynaud's phenomenon, as well as the coldness, numbness and pain of Raynaud's phenomenon. Respiratory failure, as estimated by Hugh-Jones classification, was significantly decreased, whereas the percentage carbon monoxide diffusion capacity was significantly increased. The mean pulmonary arterial pressure decreased significantly, as did plasma fibrinopeptide A, beta-thromboglobulin and platelet factor 4. There was no significant change in LVEF after 2 or 12 months, but after 12 months of SH administration, RVEF increased significantly. In conclusion, use of SH may prevent Raynaud's phenomenon, respiratory failure and right ventricular failure in patients with systemic sclerosis. PMID- 11191718 TI - The association of low serum cholesterol with depression and suicidal behaviours: new hypotheses for the missing link. AB - Several observational studies indicate that reduction of serum cholesterol levels is related to an increase in violent deaths and suicide but the nature of this possible relationship remains unclear. Many confounding factors, e.g. poor health, depression and loss of appetite may play a role in the apparent relationship between serum cholesterol levels and suicide. Two separate phenomena should be considered: lowering total cholesterol and low total cholesterol. This review considers the evidence from epidemiological studies on serum cholesterol lowering and psychiatric disturbances. The available evidence does not seem to substantiate the view that large-scale intervention to reduce cholesterol concentrations could lead to more violent and aggressive behaviour, and generally greater unhappiness. In recent trials using statin treatment, there were slightly fewer deaths from accidents and suicide in the treated group compared with the placebo group. We believe that clinicians should not be deterred from prescribing cholesterol-lowering drugs, to reduce the risk of death from coronary heart disease, when they are indicated. PMID- 11191720 TI - Lonidamine cytotoxicity: involvement of the lysosomal compartment. AB - Lonidamine (LND) was found to decrease significantly the pH gradient across intracellular compartments in Ehrlich ascites tumour cells. The effect was maximal in the range 0.2 - 0.3 mM LND, and was observed both in the presence of glucose - i.e. conditions in which a high bioenergetic status of the cells was maintained by glycolysis (due to a strong Crabtree effect in these cells) - and in the absence of glucose. Moreover the LND effect was also observed in the presence of bafilomycin, a specific inhibitor of the H+ -vacuolar ATP-ase. Based on these findings, we suggest that the LND effect on the proton gradient reflects an LND-induced increase in membrane proton conductance. The consequent impairment of intracellular proton gradients might be involved in the mechanism of action of LND, allowing drugs that are weak bases to accumulate preferentially in the cytoplasm and nucleus. PMID- 11191721 TI - Autologous serum deprivation restored IL-1 receptor antagonist production by peripheral blood mononuclear cells in patients with gastric cancer. AB - It has been established that cancer patients have immunosuppressive substances in their sera that depress cellular immunity. Although plasma exchanges have been attempted to remove these substances and to improve immunity to cancer, little is known about its mechanism from the viewpoint of cytokine pattern. The levels of the cytokines, tumour necrosis factor-alpha, interleukin 1beta, interleukin 6, interferon-gamma and interleukin-1 receptor antagonist (IL-1ra) by peripheral blood mononuclear cells (PBMC) were determined simultaneously by the whole-blood assay and the PBMC assay in 20 patients with gastric cancer and in 10 healthy volunteers. In both assays the cytokine levels were lower in patients with cancer compared with healthy controls, with the exception of IL-1ra. In the PBMC assay, the IL-1ra level in cancer patients was significantly higher than that in controls. No statistical correlation between the cytokine levels determined by the two assays was found. We suggest that autologous serum deprivation restored and enhanced IL-1ra production, and normalized the cytokine cascade in immune response, in patients with gastric cancer. PMID- 11191722 TI - Clinical study of cefpirome sulphate in obstetric and gynaecological infections. AB - Cefpirome sulphate is a fourth-generation cephem antibiotic, which has a broad spectrum of antibacterial activity against Gram-positive and -negative bacteria, and is highly stable to beta-lactamase. Cefpirome sulphate was administered to 166 patients with obstetric or gynaecological infections, and its clinical and antibacterial effect was evaluable in 139. Excluding seven patients who violated the study protocol by receiving concomitant drugs, the safety of cefpirome sulphate was assessed in 159 patients. In the 139 patients in whom efficacy was evaluated, the improvement rate was 80.6% (112/139) and the eradication rate 72.6% (45/62). The eradication rate for bacteria isolated from the patients at the start of the study was 84.7% (111/131). No resistance to cefpirome sulphate was observed in Enterococcus faecalis or Bacteroides species. Systemic erythema and nausea each occurred in one patient, and nine patients showed abnormal hepatic function test results. These results suggest that cefpirome sulphate is effective in the treatment of obstetric and gynaecological infections and has a good side-effect profile. PMID- 11191723 TI - Drug-resistant tuberculosis at the University Hospital in Gaziantep, South eastern Turkey. AB - We aimed to determine the present status of drug resistance of Mycobacterium tuberculosis at the Gaziantep University Hospital in south-east Turkey. Data for 1995 to 1999 were retrospectively evaluated with respect to smear-positive cases, first positive culture for Mycobacterium tuberculosis for each patient and drug susceptibility tests for the major antituberculous drugs. Cultures were done using the Bactec 460 TB method. A total of 106 (40.2%) strains were resistant to at least one drug. Single drug resistance was observed in 47 strains (17.8%) and resistance to two or three drugs was found in 28 and 29 strains (10.6 and 11.0%), respectively. Two strains (0.8%) were resistant to all four drugs. While multidrug resistance was observed in 52 (19.7%) strains, resistance to isoniazid + rifampin was observed in 20 (7.6%) strains. This retrospective study showed that combined drug resistance of M. tuberculosis is highly prevalent in southeastern Turkey. Possible reasons for the failure of current control policies were considered. PMID- 11191724 TI - Results of conversion total hip prosthesis performed following painful hemiarthroplasty. AB - Fifteen of 18 cases who underwent conversion total hip prosthesis due to painful hemiarthroplasty, between 1992 and 1997, were investigated retrospectively. The 13 (86.6%) women and two (13.4%) men (mean age, 59 years) were followed up for an average of 32 months. Pre-operative and post-operative Harris hip scores were 36.4 (28 - 42) and 85.9 (69 - 98), respectively. In all cases the femoral component had more than 2 mm radiolucency in Gruen zones I, IV and VII, and five cases had acetabular protrusion; other cases had cartilage erosion. In the last follow-up of conversion total hip prosthesis, there was no radiolucency in either femoral or acetabular components. Comparing our results of conversion total hip prosthesis with primary total hip prosthesis results for femoral neck fractures in the literature we conclude that, in elderly patients with femoral neck fractures, primary total hip prosthesis has better results. PMID- 11191725 TI - Effects of cancer chemotherapy on the blood fibrinogen concentrations of cancer patients. AB - Blood fibrinogen concentrations and glutamic-pyruvic transaminase activities of 66 adult cancer inpatients (aged 22 - 70 years) were determined both before and after one or two chemotherapy regimens. The percentage of hepatoma patients with abnormal blood fibrinogen levels (< 1.5 or > 6.0 g/l) was higher (64.3% of 14 patients) than that in other cancer categories (19.2% of 52 patients). The mean blood fibrinogen concentrations of male (3.5 g/l) and female (4.5 g/l) cancer patients were higher than those previously reported for healthy humans (2.8 and 2.9 g/l, respectively). After chemotherapy, blood fibrinogen concentrations decreased in patients whose primary tumours were surgically removed (from 4.8 to 3.2 g/l) but increased (from 3.0 to 4.8 g/l) in those who did not undergo surgery. Glutamic-pyruvic transaminase activities did not appear to be related to blood fibrinogen levels. We conclude that the increase in mean blood fibrinogen levels of cancer patients is probably related to tumour growth. Different mechanisms may operate in patients with hepatoma. PMID- 11191726 TI - Isolated factor VII deficiency diagnosed after a life-threatening brain haemorrhage. AB - A 65-year-old man was admitted to another hospital with a life-threatening brain haemorrhage, and laboratory examinations on admission revealed prolonged prothrombin time with normal activated partial thromboplastin time. To establish the cause of his abnormal coagulation, he was referred to our clinic. Neither the patient nor his family had any previous history of bleeding symptoms. His liver function was within normal limits but coagulation tests showed increased plasma activities of factors II, VIII, IX, X, with reduced activities of factors V and VII. The activity of factor VII was less than 2% but no inhibitor of factor VII was detected in the plasma. We concluded that the patient had a rare congenital isolated factor VII deficiency although he had not shown earlier bleeding problems, presumably because of compensation for the factor VII deficiency by enhanced activities of components of the extrinsic coagulation pathway, factors II, VIII, IX and X. PMID- 11191727 TI - The frequency and cost of patient-initiated device removal in the ICU. AB - OBJECTIVE: To determine the frequency and pattern with which patients in the intensive care unit (ICU) remove medical devices on their own, and the costs associated with this problem. DESIGN: Prospective observational study. SETTING: Two 10-bed sections of a multidisciplinary ICU in a tertiary care teaching hospital. PATIENTS: Adults admitted to the ICU for longer than 24 hours during October 1998. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records were reviewed prospectively for the occurrence of patient-initiated device removal and the responses to those events by health care providers. Associated costs were estimated using hospital databases and Medicare physician reimbursement schedules. Annual cost estimates were calculated using 1997 admission statistics for 1211 adults in an ICU for more than 24 hours. Thirty-six patients were studied for 199 patient-days. Ten patients (28%) removed 42 devices: 88% of these events involved gastrointestinal tubes and vascular catheters. Significant agitation was documented within 2 hours before 74% of the events. Estimated cost associated with device removal was $7606, or $181/event. The estimated annual cost in this 42-bed ICU was more than $250,000. CONCLUSIONS: Patients commonly remove medical devices on their own, and this represents significant consumption of health care resources. PMID- 11191728 TI - Aseptic meningitis after intraventricular administration of gentamicin. PMID- 11191729 TI - Elevation of hepatic transaminases after enoxaparin use: case report and review of unfractionated and low-molecular-weight heparin-induced hepatotoxicity. AB - Enoxaparin, a low-molecular-weight heparin (LMWH), is widely used for the treatment and prophylaxis of thromboembolic disorders, such as deep vein thrombosis. Low-molecular-weight heparin products have smaller and more uniform molecular weights than unfractionated heparin, allowing them to exhibit a much greater affinity for factor Xa than factor IIa. Compared with traditional unfractionated heparin, LMWHs have proved to be equally efficacious and may be safer. The distinctive characteristics of LMWHs have resulted in decreased rates of bleeding and equivalent rates of thrombocytopenia compared with unfractionated heparin. This favorable safety profile has been identified in several studies and may have led clinicians to believe that LMWHs have lower frequencies of all common side effects. A 66-year-old woman developed increased hepatic transaminases during treatment with enoxaparin for a deep vein thrombosis; they returned to normal after enoxaparin discontinuation. A causal relationship between unfractionated heparin and asymptomatic, transient increases in hepatic transaminase levels has been documented; these increased levels also appear to be an underrecognized, adverse effect of LMWH therapy. PMID- 11191730 TI - Phosphorylation of nucleoside analog antiretrovirals: a review for clinicians. AB - Nucleoside analogs (zidovudine, didanosine, zalcitabine, stavudine, abacavir, lamivudine) have been administered as antiretroviral agents for more than a decade. They undergo anabolic phosphorylation by intracellular kinases to form triphosphates, which inhibit human immunodeficiency virus replication by competitively inhibiting viral reverse transcriptase. Numerous methods are used to elucidate the intracellular metabolic pathways of these agents. Intracellular and extracellular factors affect intracellular phosphorylation. Lack of standardization and complexity of methods used to study phosphorylation in patients limit interpretation of study results and comparability of findings across studies. However, in vitro and in vivo studies give important insights into mechanisms of action, metabolic feedback mechanisms, antiviral effects, and mechanisms of toxicity, and have influenced dosing regimens of nucleoside analogs. PMID- 11191731 TI - Visual disturbance associated with celecoxib. AB - Celecoxib, a specific inhibitor of cyclooxygenase-2, is used to treat the symptoms of arthritis. A 79-year-old woman developed an atypical visual disturbance associated with this agent that resolved on discontinuation of celecoxib. Similar visual disturbances described with the traditional nonsteroidal antiinflammatory drugs are discussed. PMID- 11191732 TI - A vision of pharmacy's future roles, responsibilities, and manpower needs in the United States. Introduction to commentaries. PMID- 11191733 TI - A vision of pharmacy's future roles, responsibilities, and manpower needs in the United States. American Council on Pharmaceutical Education. PMID- 11191734 TI - A vision of pharmacy's future roles, responsibilities, and manpower needs in the United States. American Pharmaceutical Association. PMID- 11191735 TI - A vision of pharmacy's future roles, responsibilities, and manpower needs in the United States. American Society of Health-System Pharmacists. PMID- 11191736 TI - A vision of pharmacy's future roles, responsibilities, and manpower needs in the United States. Board of Pharmaceutical Specialties. PMID- 11191737 TI - Gatifloxacin, an advanced 8-methoxy fluoroquinolone. AB - Gatifloxacin is a new 8-methoxy-fluoroquinolone antibiotic approved for use in the United States in December 1999. It has a broad spectrum of activity with potent activity against gram-positive bacteria, including penicillin-resistant Streptococcus pneumoniae, as well as excellent activity against gram-negative and atypical organisms. Gatifloxacin is available in both oral and injectable forms and is administered once/day. Bioavailability is 96%, with a plasma half-life of approximately 8 hours in individuals with normal renal function. Elimination is primarily renal excretion of unchanged drug with no cytochrome P450-mediated metabolism. The drug is distributed extensively into tissues and fluids and has a favorable pharmacodynamic profile against important pathogens. It had excellent efficacy in clinical studies of acute sinusitis, acute bacterial exacerbations of chronic bronchitis, community-acquired pneumonia, complicated and uncomplicated urinary tract infections and pyelonephritis, skin and skin structure infections, and uncomplicated gonococcal infections. The agent is well tolerated, with no evidence of hepatic, cardiac, or phototoxicity noted thus far. Drug interactions are uncommon; however, like other fluoroquinolones, coadministration with multivalent cations should be avoided due to significantly decreased absorption. Gatifloxacin should prove to be a safe and effective agent for a wide variety of infections. PMID- 11191738 TI - Misoprostol therapeutics revisited. AB - Misoprostol, a prostaglandin E1 analog, is a racemate of four stereoisomers. On administration it rapidly de-esterifies to its active form, misoprostolic acid. Misoprostolic acid is 85% albumin bound and has a half-life of approximately 30 minutes. It is excreted in urine as inactive metabolites. No significant drug interactions have been reported. Besides its gastrointestinal protective and uterotonic activities, misoprostol regulates various immunologic cascades. It inhibits platelet-activating factor and leukocyte adherence, and modulates adhesion molecule expression. It protects against gut irradiation injury, experimental gastric cancer, enteropathy, and constipation. It improves nutrient absorption in cystic fibrosis. Misoprostol has utility in acetaminophen and ethanol hepatotoxicity, hepatitis, and fibrosis. It is effective in asthmatics and aspirin-sensitive asthmatic and allergic patients. It lowers cholesterol and severity of peripheral vascular diseases, prolongs survival of cardiac and kidney transplantation, synergizes cyclosporine, and protects against cyclosporine induced renal damage. It works against drug-induced renal damage, interstitial cystitis, lupus nephritis, and hepatorenal syndrome. It is useful in periodontal disease and dental repair. Misoprostol enhances glycosoaminoglycan synthesis in cartilage after injury. It prevents ultraviolet-induced cataracts and reduces intraocular pressure in glaucoma and ocular hypertension. It synergizes antiinflammatory and analgesic effects of diclofenac or colchicine and has been administered to treat trigeminal neuralgic pain. It reduces chemotherapy-induced hair loss and recovery time from burn injury, and is effective in treating sepsis, multiple sclerosis, and pancreatitis. PMID- 11191739 TI - A multicenter evaluation of gentamicin therapy in the neonatal intensive care unit. AB - STUDY OBJECTIVE: To evaluate traditional nomogram (TN) versus individualized pharmacokinetic gentamicin dosing practices in neonatal intensive care units, focusing on achieving target therapeutic concentrations (peak > 8 microg/ml, trough < 2 microg/ml), number of dosing changes, number of concentrations obtained, and evidence of nephrotoxicity. DESIGN: Retrospective chart review. SETTING: Three neonatal intensive care units. PATIENTS: Three hundred nine infants prescribed gentamicin. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Sixty-seven percent of patients receiving pharmacokinetic dosing had initial peak concentrations of 8 microg/ml or greater compared with 7% of patients receiving TN dosing (p<0.001). Trough concentrations exceeding 2 microg/ml were reported in 23% of patients receiving TN dosing compared with 2% of pharmacokinetic-dosed patients (p<0.001). Forty-two percent and 6%, respectively, required dosage adjustments (p<0.01). The mean number of concentrations obtained per patient was 2.8 and 2.1, respectively (p<0.01). Neither group had evidence of gentamicin related nephrotoxicity. CONCLUSION: Compared with TN dosing, administering gentamicin loading doses and performing initial pharmacokinetic analysis resulted in rapid attainment of desired concentrations and fewer dosage adjustments, and allowed for a decrease in the number of gentamicin concentrations. PMID- 11191740 TI - Pharmacotherapy of behavioral and psychological symptoms of dementia: time for a different paradigm? AB - Behavioral and psychological symptoms of dementia can occur in 60-80% of patients with Alzheimer's disease or other dementing illnesses, and are important in that they are a source of significant caregiver stress and often precipitate nursing home placement. These symptoms, namely, aggression, delusions, hallucinations, apathy, anxiety, and depression, are clinically managed with a variety of psychotropic drugs such as antipsychotics, antidepressants, antiepileptic drugs, and benzodiazepines. Various advances in the neuropathophysiology and pharmacotherapy must be considered in the optimal design of regimens for patients with these symptoms. PMID- 11191741 TI - [The phenomenon of rectangularization of the survival curve in the Czech population as a result of the concept of successful aging and geriatric medicine]. AB - An overview of conceptions of the successful ageing with positive impacts on the improvement of the quality of life, on decreased dependence in activities of daily living, and on demands for health-social care in senescence is given. Necessity of altering of sanitary services and outlooks on the geriatric patients corresponding to the demographic development and improvement of their functional state is stressed. Concepts of the upgrowth of the life expectancy are given. The phenomenon of rectangularization of the survival curve in the population of the Czech Republic during the 20th century is demonstrated and the prospect till the middle of 21st century for the population structure, life expectancy, longevity index are presented. PMID- 11191742 TI - [Ambulatory monitoring of blood pressure--focus on childhood]. AB - Conventional office measurements of blood pressure (BP) are limited in their ability to assess long term hemodynamic load on cardiovascular system. The ambulatory blood pressure monitoring (ABPM) offers the advantage of providing multiple blood pressure measurements from a subject's normal environment during his normal activities, thereby revealing important patterns of blood pressure during the whole 24-hour period. Results of ABPM have much better correlation with end organ damage than casual BP and provide more sensitive data of ultimate prognosis. There is much better long-term reproducibility of ambulatory blood pressure compared with conventional office BP measurements. The phenomenon of "white coat" hypertension (WCH) defined as mean office BP readings in the hypertensive range but ambulatory blood pressure (ABP) readings in the normal range represents probably a benign entity not requiring pharmacological treatment. Based on normal population of school children and adolescents the percentiles of ABP have been recently established and patterns of ABP have been studied in children in various clinical settings. WCH has been recognized in childhood and its prevalence seems to be higher comparing with adult population. ABPM seems to be an effective and well tolerated tool in evaluating BP in children and adolescents helping to identify those who need careful checkup and treatment. PMID- 11191743 TI - [Significance and prevalence of the C282Y gene mutation of primary hemochromatosis in the pathogenesis of pophyria cutanea tarda]. AB - BACKGROUND: Hitherto studies on the ethiopathogenesis of porphyria cutanea tarda (PCT) show that the major pathogenic factor is iron ion, which acts via inhibition of the uroporphyrinogen decarboxylase. New speculations have appeared on the possible relation of this role of iron and the occurrence of mutation of the recently discovered gene of the hereditary hemochromatosis HFE, which may cause the iron overloading of the organism. Our paper describes prevalence of the C282Y gene mutation (HFE) together with the clinical and laboratory record in PCT patients. METHODS AND RESULTS: PCT was diagnosed mostly on the basis of clinical finding of actinic-traumatic vesicular dermatitis and the typical laboratory record of elevated higher-carboxylic porphyrines in urine and stool. Other laboratory methods tested the liver functions, plasma iron level and its binding capacity, ferritine level. All patient underwent routine haematological testing. Presence of antibodies against hepatitis C was also assayed (Elisa test 2nd generation, Sanofi Pasteur). In patients with prominent laboratory alterations showing possibility of the hepatic structural lesion, histology from the liver punctate was done. Frequency data of the C282Y gene mutation (HFE) in PCT patients was estimated on the basis of the genetic testing using PCR reaction of our own system. Group of PCT patients had 69 persons (63 patients with the sporadic form and 6 patients with familiar form of the disease). Hereditary haemochromatosis C282Y gene mutation (HH) was found in 15 patients, three of them were homozygotes and twelve heterozygotes (three heterozygotes had the familiar form of the disease). Nobody in this group was positive in the HIV antibody testing. In all porphyria patients with the presence of mutated gene who underwent liver biopsy, siderosis of different degrees was identified. In three patients neither the phenotypic observation nor the laboratory testing have shown haemochromatosis. Prevalence of C282Y gene mutation HFE in patients with porphyria cutanea tarda was studied. Such mutation was found in 15 persons (12 heterozygotes and 3 homozygotes) from the group of 69 tested patients (21.7%). Such frequency is significantly higher than in the control--nonporphyric--persons (10%). Patients were without clinical symptoms. Laboratory haematological changes, typical for HH, manifested in some of them only (elevated level of ferritine was found in 10 from 15 porphyria patients, elevated sideremia in one of them). Red blood cell counts were in both homo- and heterozygotes normal. Concurrence of the two porphyrinogenic factors--presence of gene mutation HFE and hepatitis C infection--was not proved. Antibodies against hepatitis C virus were not identified in any of the patients. Siderosis was found to be only a symptomatic sign, which was pronounced in different degree in all 9 porphyria patients with C282Y gene mutation who underwent liver biopsy. CONCLUSIONS: Frequency of C282Y gene mutation in our patients with porphyria cutanea tarda appears similar to that in other Middle European countries. It differs significantly from the frequency found in South European and North European countries (British). PMID- 11191744 TI - [Relation between serum leptin levels, blood parameters and erythropoietin levels in hemodialyzed patients]. AB - BACKGROUND: Serum leptin levels are significantly increased in hemodialysed patients compared to healthy subjects. There are some data suggesting the possible relationship of leptin and the regulation of haematopoiesis. The aim of our study was to compare serum leptin levels in two groups of hemodialysed patients: the group treated by recombinant human erythropoietin (n = 40) (HD + EPO), the group without erythropoietin treatment (HD) and the control group of healthy subjects (n = 20) to explore the influence of erythropoietin treatment on serum leptin levels. METHODS AND RESULTS: The tendency towards lower body fat content and higher serum leptin levels was found in both groups of HD patients compared to control group, but the differences did not reach statistical significance due to high variability of those parameters (leptinu levels: HD 19.5 +/- 18.5, HD + EPO 24.9 +/- 23.3, K 10.4 +/- 8.8 ng.ml-1). The erythrocyte count and haemoglobin levels in both groups of HD patients were significantly lower than in control group. The erythrocyte count and haemoglobin levels were significantly lower in HD patients treated by erythropoietin compared to untreated HD group. The leptin/body fat content ratio was significantly higher in HD patients compared to healthy subjects (HD 0.86 +/- 0.72, HD + EPO 0.92 +/- 0.78, K 0.35 +/- 0.21, p < 0.05). Serum leptin levels in all studied groups correlated positively with body fat content and negatively with erythrocyte count. No significant relationships of serum leptin levels to erythropoietin levels or other parameters studied were found in any of groups. CONCLUSIONS: Our study further supported the fact that serum leptin levels in HD patients are relatively higher than in healthy subjects. Serum leptin levels in HD patients treated by recombinant human erythropoietin did not significantly differ from HD patients without this treatment. Except of the negative correlation between serum leptin levels and the erythrocyte count no statistically significant relationships of serum leptin levels and the blood count parameters were found. PMID- 11191745 TI - [Organ-specific antibodies in children with idiopathic inflammatory bowel disease and their use in clinical practice]. AB - BACKGROUND: Ethiopathogenesis of the idiopathic inflammatory bowel disease has not been yet fully explained. Several abnormalities of the humoral immunity supporting the concept of autoimmune character of the disease have been identified. The aim of our study was to characterise occurrence of the organ specific antibodies against the intestinal goblet cells and against acinar cells of the exocrine pancreatic tissue and to evaluate their significance for the diagnostics of the idiopathic inflammatory bowel disease. METHODS AND RESULTS: 69 children were included in the study. The group consisted of 20 patients with idiopathic proctocolitis (11 boys and 9 girls, 6 to 18 years old, average age 15.5) and 14 patients with Crohn's disease (9 boys and 5 girls, 5 to 18 years old, average age 14.7). Control group included 35 children (20 boys and 15 girls, average age 14.7). In patients of the idiopathic proctocolitis group, antibodies against the intestinal goblet cells were assayed by indirect immunofluorescence method in 55%. In patients with Crohn's disease, antibodies against acinar cells of the exocrine pancreatic tissue were found in 64.2%. Differences in manifestation of antibodies against acinar cells of the exocrine pancreatic tissue in Crohn's disease were statistically significant (p = 0.001). Statistically significant (p = 0.01) was also the difference of levels of antibodies against the intestinal goblet cells in patients with idiopathic proctocolitis when compared to patients with Crohn's disease. Statistically significant difference (p = 0.01) was found in levels of antibodies against acinar cells of the exocrine pancreatic tissue in Crohns disease and antibodies against the intestinal goblet cells in patients with idiopathic proctocolitis. CONCLUSION: Testing on presence of specific antibodies against acinar cells of the exocrine pancreatic tissue and against intestinal goblet cells is a valuable tool for the diagnostics of the idiopathic inflammatory bowel disease in childhood and adolescence. PMID- 11191746 TI - [Tuberculosis in the Czech Republic in 1999]. AB - Report is given on the tuberculosis (TB) prevalence and the new diseases monitoring in Czech Republic (CR) in 1999 using the register of notifiable TB diseases. 1631 new TB cases and relapse were notified (15.9/100,000 citizens). Majority TB cases, 1369 (13.3/100,000 citizens) were of the respiratory system and 262 TB cases were in other locations. 63% of the respiratory system diseases were bacteriologically verified. In comparison with the year 1998, the number of newly notified TB patients was 9.6% lower, number of TB cases of the respiratory system which were bacteriologically verified was 12.3% lower, cases of microscopically positive TB were 17.4% less frequent. Among the notified TB patients there were 91 foreigners. TB relapse was identified in 61 patients. Among the notified TB cases, 987 (60.5%) were males and 644 (39.5%) were females. In both sexes patients over 65 predominated. Prevalence of TB cases higher than the average for the whole state was found in Prague, northern and western Bohemia. Groups with TB prevalence higher than 50/100,000 citizens were identified (the risk groups). They include homeless people, drug addicts, asylum applicants, and prisoners. Due to subjective troubles of patients TB was diagnosed in 70.2% cases, by active investigation in 13.9% patients. Late TB diagnosis at autopsy came in 6.8% cases. Decease due to TB was notified in 79 patients. In 77 of them TB had not been diagnosed premortally. 106 new cases and relapses of non-TB mycobacterial disease were notified in 1999. The case of tuberculosis in CR was in 1999 restrainable. In comparison with 1998 significant decrease of TB prevalence in individual subgroups of TB disease was described (10 to 17%). Also the decrease of the long-term trend (10 years) of newly notified TB patients and TB of the respiratory system was depicted. It is necessary to maintain the quality and extend of the TB control program in order to prevent the new outbreak of TB disease. PMID- 11191747 TI - [Detection of minimal residual disease in Ewing's sarcoma using RT-PCR]. AB - BACKGROUND: More than 90% of Ewing's sarcomas (ES) contain a fusion of the EWS and FLI-1 genes, due to the t(11;22)(q23;q12) translocation. At the molecular level, the EWS-FLI-1 rearrangement shows great diversity. Specifically, many different combinations of exons from EWS-FLI-1 encode in-frame fusion transcripts and result in differences in length and composition of the chimeric protein, which function as an oncogenic aberrant transcription factor. The finding of this translocation gives evidence for the presence of ES cells. The aim of this prospective study was to verify applicability of the RT-PCR method for the detection of minimal residual disease in patients with ES. METHODS AND RESULTS: Conditions for the detection of Ewing's sarcoma cells by means of the reverse transcriptase polymerase chain reaction (RT-PCR) at fusion transcripts in peripheral blood, bone marrow (BM) and autologous hematopoietic stem cell grafts in patients with ES were appointed. 31 samples of BM, 5 samples of blood and 7 peripheral blood grafts obtained from 23 patients were investigated. Presence of tumor cells was identified in 7 BM samples from 7 different patients (31 samples from 16 patients), all the peripheral blood and graft samples were negative. CONCLUSIONS: The high sensitivity of RT-PCR method in detection of cells bearing t(11;22)(q23;q12) was demonstrated in the experimental model and clinical samples. Likewise the literary statements, the RT-PCR method was found to be more sensitive than cytology. PMID- 11191748 TI - [Combined therapy of acromegaly with a combination of lanreotide and terguride]. AB - BACKGROUND: The aim of the treatment of acromegaly is to normalise the hormonal activity. Besides the surgical and radiation treatment, medical therapy can be used. The project was set to determine the value of combined therapy with lanreotide and terguride in patients with active acromegaly. METHODS AND RESULTS: Nine patients previously treated with lanreotide for at least one year without normalisation of hormonal activity were included in the study. Terguride was added to lanreotide for one month. The combined treatment brought about reduction of growth hormone (GH) levels, however, with marginal significance only. GH-BP, IGF-I and IGFBP-3 serum levels were not changed significantly. Considering the individual cases, the combined treatment resulted in normalisation of GH levels in one patient and that of IGF-I in another one. Substantial decrease of GH levels (> 50%) was found in three patients and that of IGF-I (> 20%) in another one patient. CONCLUSIONS: The combined treatment of acromegaly appears to be more effective than monotherapy with lanreotide only in a subset of acromegalic patients. PMID- 11191749 TI - [Development of epidemiologic indicators in the diagnosis and therapy of pulmonary cancer in the Czech Republic 1970-1999]. AB - BACKGROUND: Lung cancer (LC) remains serious medical and social problem. In US it represents the most frequent cause of malignancy-related deaths both in males and females. In Czech Republic about 6000 persons acquires LC each year. The aim of the study was to describe developmental trends of the mortality, methods of therapy and results of treatment in Czech Republic during the last 30 years. METHODS AND RESULTS: Prevalence of LC in males reached maximum in the middle of seventies (104/100,000), in females it has still the increasing tendency, being highest in 1996 (22.8/100,000). Comparing the swiftness of diagnostics: In years 1985 to 1996 number of late diagnosed cases diminished and the operability of all diagnosed cases increased from 10.4% to 11.8% in males and from 9.4% to 11.2% in females. The most frequent type of LC is the epidermoid type reaching in 1998 52% of all cases in the CR and 47% of cases treated at the TRN department of the Second Medical Faculty. Result of the five years survival have been still unsatisfying, only 4% of males and 5.3% females live longer than five years. At the department of TRN of the Second Medical Faculty in years 1998 and 1999, 266 cases of LC were diagnosed. The male/female ratio was 2:1, 21.9% were at first or second stadium. Following treatment was employed: 24.4% of all diagnosed cases were sent to surgery, 40% underwent radiotherapy, 94.3% of patients with parvocellular LC and 22% of non parvocellular LC received chemotherapy. CONCLUSIONS: In Czech Republic during the last 25 years numbers of males with LC stagnate at inacceptable high values, in females the incidence still progresses. Unsatisfying are the results of treatment, numbers of patients surviving longer than 5 years are lower than in most of developed countries. To improve the situation it would be necessary to limit smoking habits in the population, reassess possibilities of depiction of early phases of LC, and improve the therapy employing modern approaches as the neoadjuvant chemotherapy, contemporary chemotherapeutic regimes in combination with radiotherapy or surgical therapy. PMID- 11191750 TI - [Dialysis therapy in the Czech Republic in 1999]. AB - Number of HDS patients has stabilised; however, the technical background of the haemodialysation program is not sufficient, 40% of the dialysation monitors has been amortised. In the dialysed population numbers of elderly patients (60%) and diabetics (33%) rise, thus rise the number of polymorbid patients and about 1/3 of new patients come form "the street". Not surprisingly it brings high mortality (20%). Six per cent of patients were treated with peritoneal dialysis in 1999, the highest number achieved in the present history of this method. This trend should be kept in future. PMID- 11191751 TI - [Chemoprevention of bronchogenic carcinoma]. AB - Lung cancer is the leading cause of cancer-related deaths in many developed countries. Understanding its carcinogenesis is critical for the development of rational approaches to cancer prevention. The concept of chemoprevention is based on the idea that the diffuse injury of the respiratory epithelium results from chronic carcinogen exposure. Chemoprevention agents should reverse or suppress the development of premalignant and malignant changes by different mechanisms. In the future, the clinical application to risk groups of patients could lead to substantially decreased frequency of the lung cancer. The results of ongoing trials are eagerly awaited. PMID- 11191752 TI - [A pathology reminder in the case report by L. Jankovec, Z. Rysavy, P. Tesinsky, S. Lacinova: Systemic general amyloidosis with kidney involvement]. PMID- 11191753 TI - [A historical review and some comments on the nuclear transplantation in fish]. AB - In this review article, a brief history and main results of the studies on the nuclear transplantation (cloning) in fish was introduced. Late Professor T. C. Tung (TONG Di-Zhou), a noted Chinese Experimental Embryologist and his research group at the Institute of Zoology, the Chinese Academy of Sciences (CAS) in Beijing, China initiated and established successful technology of nuclear transplantation in fish in 1963. During the past 36 years, most of the studies on fish cloning were performed mainly by Chinese groups except only one article was published by authors in former USSR (Gasaryan et al. 1979), and the other one was published by Japanese authors in Japan (Niwa et al. 1999). The primary goals of the studies of Tung's group were: (1) to study the inter-relationship between the nucleus and the cytoplasm in terms of the controlling effects determined by nucleus or cytoplasm or both during the ontogenesis, cell differentiation and phenotypic expression in a developing animal; and (2) to produce fish clones of commercial importance for agricultural purposes. The most successful results that have been obtained by Tung's group in collaboration with the investigators at various fisheries institutions in China were the production of nucleocytoplasmic adult hybrid fish between different varieties, species, genera and subfamilies that produced viable offspring. Furthermore, these nucleocytoplasmic fish hybrid revealed that while most phenotypic characteristics are controlled by the nucleus, a few are controlled by the cytoplasm or by both. In addition, the resulting nucleocytoplasmic fish hybrids also showed some better characteristics of economic importance such as faster growth rate, increasing of protein content and reducing of fat content in muscle, etc. So far, no such kinds of evidences are available either in amphibian or in mammals. Another most important result obtained by other Chinese groups showed that the uncultured or cultured adult somatic cell in fish which can support the nuclear transplanted eggs developing into adults. They were: (1) a 17 month old gold-fish obtained by transplanting an adult erythrocytes into an enucleated egg (WU et al. 1982); (2) a subcultured kidney cell nucleus of Crucian carp (Carassius auratus) can support the transplanted enucleated egg of same species developing into a three years old adult with female sexual characteristics (CHEN et al. 1986) and (3) a cultured liver cell nucleus from grass carp (Ctenopharyngoden idellus) can support a nuclear transplanted unfertilized egg of the same species developing into an adult fish at least of one year old when that paper was published. Some discussions and comments for evaluating the results obtained from previous studies and suggestions for further investigations in this research field are also provided. More detailed information could be found in the book--"Cloning in Fish-nucleocytoplasmic Hybrids" which was written by Shaoyi Yan in English and published by International Union of Biological Sciences and Educational and Cultural Press Ltd. Hong Kong in 1998. PMID- 11191754 TI - [Progress on studies of nikkomycin structure and some genes related to nikkomycin biosynthesis]. AB - Nikkomycin is a kind of new antifungal antibiotics. More than 20 biologically active nikkomycin structures have been isolated and the main active structures are nikkomycins X, Z, I, J. Here, we introduce the progress on the studies of nikkomycin structures, the relationships between nikkomycin structure and biological activity, and genes related to nikkomycin biosynthesis. PMID- 11191755 TI - [Studies on the construction and expression of recombinant human fusion gene Nm23 H1/HbFGF in Escherichia coli]. AB - First, a piece of intermediate nucleic acid chain was designed according to the nucleic acid sequences of Nm23-H1 and HbFGF cDNA, then it was combined with the upstream primer of Nm23-H1 or the downstream primer of HbFGF to perform Polymerase Chain Reaction (PCR) respectively. The fusion gene Nm23-H1/HbFGF was constructed by four steps of PCR, and it was cloned into the plasmid vector pBV220. The recombinant was induced at 42 degrees C and analyzed by SDS-PAGE. Results show that the fusion gene Nm23-H1/HbFGF highly expresses its product in inclusion body in E. coli BL21(DE3). The expressing product is 14% of the total bacterial protein and it is 34 kD. ELISA assay and Western blot indicate that the inclusion body contains antigens of Nm23-H1 and HbFGF. By denaturation, renaturation and purification, the inclusion body was purified. Determination and biological activity assay show that the purified product contains two kinds of antigens which have biological activities of Nm23-H1 and HbFGF. All these data establish good base to study the tumor suppressor activity and oncogenicity of the fusion gene Nm23-H1/HbFGF in eukaryocyte. PMID- 11191756 TI - [Gene cloning, expression and purification of its production of recombinant human superoxide dismutase]. AB - Human SOD cDNA was cloned and constructed an expression plasmid with high sufficient and stabilility expression in E. coli. The rhSOD cDNA was amplified by RT-PCR with the template of the total RNA extracted from human liver tissue. The expression plasmid, pLY-4/rhSOD, containing rhSOD cDNA, was transformed into the E. coli JF1125. The sequence of the cloned rhSOD cDNA was identified with the reported data. The expression level reached to more than 68% of total bacteria proteins; The technology for protein renature and purification was efficiency and fast. The purity of the final products reached more than 98%. The value of bioactivity was determined as 2529 u/mg. This study gave enough support for production of rhSOD by biotechnology. PMID- 11191757 TI - [Expression of human GDNF in methyltrophic yeast Pichia pastoris and silkworm larvae]. AB - The cDNA encoding glial cell derived neurotrophic factor (GDNF) was cloned into the Pichia expression vector pPIC9K and then transformed into his4 mutant yeast GS115 by electroporation. Multicopy transformants were screened by various G418 concentrations and induced by methanol. The human GDNF gene was cloned into the baculovirus transfer vector pBacPAK8. The recombinant transfer vector pBacPAK GDNF was coinfected with linear Bm-BacPAK6 DNA into BmN cells. The recombinant virus was screened and plaque-purified. The silkworm larvae were infected with the recombinant virus and collected 5 days later. SDS-PAGE and Western blot confirmed that GDNF was expressed in Pichia culture medium and silkworm larvae hemolymph. The GDNF protein expressed in Pichia and silkworm larvae could significantly promote the survival and neurite outgrowth of dopaminergic neurons. PMID- 11191758 TI - [Fusion and expression of the gene encoding human Mn-SOD to anti-CEA single-chain antibody in Escherichia coli]. AB - The gene encoding human manganese-superoxide dismutase (Mn-SOD) was fused to anti carcinoembryonic antigen single-chain antibody gene to construct the fusion gene, then was ligated into prokaryotic expression vector pET-22b(+), The fusion gene was expressed in E. coli at high level, accounting for 24% of the total bacteria soluble protein; and was characterized by SDS-PAGE and Western-blot analysis; the expression product had the CEA-binding ability in RIA, and also had the SOD activity by pyrogallol autoxidation assay. So, the Mn-SOD moiety retains substantial enzymatic activity, where the ScFv moiety can deliver the fusion protein to tumor, Mn-SOD is a potential tumor-suppressor gene, maybe the fusion protein can provide a new pathway to tumor therapy. PMID- 11191759 TI - [Cloning of the zot gene of Vibrio cholerae and its expression in Escherichia coli]. AB - The zot gene encoding Zonula occludens toxin was amplified from classic Vibrio cholerae genomic DNA by PCR. The result of sequencing indicated that zot gene encodes 399 amino acid residues. The sequence of zot gene was a little bit different from that of reported including 14 nucleotides and four amino acid residues. The expression plasmid pET-ZOT was constructed by inserting zot gene into plasmid pET-28a(+) containing the T7 promoter. The expression plasmid was induced into E. coli BL21 (DE3) and expression strain BLZOT was selected. SDS PAGE analysis revealed that the ZOT protein was expressed and accumulated up to above 15% of bacterial soluble protein after induced by IPTG. A protein of 47 kD was expressed as including body. Western blot analysis revealed that the expressed protein was ZOT. PMID- 11191760 TI - [Studies of cloning and expression of rat alpha-amidase gene in Streptomyces lividans]. AB - alpha-Amidase catalyzes the C-terminal amidation of active polypeptides in the Nerve-Endocrine system. It is important for full biological activity of the polypeptides. By using the total RNA of rat atrium as a templet, the cDNA encoding alpha-amidase was amplified by RT-PCR and sequenced. The cDNA was fused with the coding sequence of mel C1 signal peptide to produce fusion gene mel/AE for secretive expression in Streptomyces lividans. The fusion gene mel/AE was inserted into plasmid pIJ680 and the recombinant plasmid pIJ-mel/AE680 was obtained. The results of SDS-PAGE and biological activity showed that the recombinant strain S. lividans TK54[pIJ-mel/AE 680] produced secretly alpha amidase. PMID- 11191761 TI - [Construction and application of an Escherichia coli high effective expression vector with an enhancer]. AB - In this study, we constructed a high effective fusion expression-vector in E. coli. This vector, pTO-T7, was characterized as: (1) an enhancer from tobacco mosaic virus (TMV), omega sequence, was ligated in front of a T7 promoter in the regulatory sequence; (2) the multi-cloning sites include eight restriction enzyme sites. It can facilitate fusion or nonfusion expression; (3) the N terminal of a fusion protein starts with the first 12 amino acids of T7 gene 10, and the C terminal is the hexahistidine tag; (4) kanmycin resistance gene was used as a selective marker. EGFP gene was inserted into pTO-T7 vector as a reporter gene. Expression data showed that fused-EGFP accounted to more than 50% of the total E. coli protein, and more than 90% of which was soluble. The fluorescence characters of fused-EGFP were also studied. The expression yield of target gene from plasmid pTO-T7 compared with that from pT-T7 without omega sequence suggested that omega sequence in pTO-T7 can improve the expression of target gene significantly. PMID- 11191762 TI - [Construction of fusion recombinant plasmid coding for RGD peptide and urokinase B chain, its expression in Escherichia coli and preliminary characterization of its biological activity]. AB - A synthetic RGD (Arg-Gly-Asp) peptide-coding sequence was fused with urokinase B chain cDNA and then cloned into the prokaryotic expression vector pBV220. The fused gene was expressed in E. coli DH5 alpha under the control of PRPL promoter by 42 degrees C induction. The expression level of the fusion protein was over 9.2% of the total bacterial proteins as a or of inactive inclusion body. The purified fusion protein was obtained with similar antigenicity as urokinase shown by Western blotting. Its in vitro fibrinolysis and anti-platelet aggregation activity was also evaluated by bioassay. PMID- 11191763 TI - [Transfer of cry1C gene into Bacillus thuringiensis by electroporation to construct strain with broader insecticidal activity]. AB - Three Transformants were selected by transferring cry1C into Bacillus thuringiensis strain YBT1535. Plasmid profiles, PCR and Southern blot result all proved that cry1C had been transferred into strain YBT1535. Bioassay results showed that the transformants of strain YBT1535 displayed significantly higher toxicity against Spodoptera exigua than strain YBT1535, but the toxicities against Heliothis armigera and Plutella xylostella did not rise except transformant YBT1535-2. PMID- 11191764 TI - [A recombinant fowlpox virus expressing the fusion protein of Newcastle disease virus strain F48E8 and its protective efficacy]. AB - The transfer vector pFGF1175-1 was constructed by insertion the fusion protein gene of Newcastle disease virus (NDV) F48E8 strain into the insertion vector pFG1175-1, downstream of P7.5 promotor, and then transfected chicken embryo fibroblast (CEF) cell cultures which had been infected with fowlpox virus (FPV) Chinese vaccine strain 282E4 for 3-4 hours. Recombinant FPV with blue plaques were selected and purified in CEF cell culture laid agar containing X-gal. The recombinant FPV named rFPV-NDF was confirmed expressing NDV fusion protein by indirect immunofluorescence assay, and could protect chickens against virulent NDV challenge, The protective rate was 96.7%. PMID- 11191765 TI - [Expression of 2.1 kb enhancin gene fragment from Helicoverpa armigera granulosis virus in Escherichia coli]. AB - The 2.1 kb fragment of enhancin gene from Helicoverpa armigera granulosis virus was inserted into vector pQE-30 and expressed successfully in E. coli M15(pREP4). The synergy of expression product(P78) on AcMNPV against the larvae of Plutella xylostella was also studied. The results indicated that the percentage of correct mortality of the larvae increased 27.88%-32.92% in 10 post-infection days. PMID- 11191766 TI - [Isolation and characterization of promoters from Phanerochaete chrysosporium]. AB - Promoter-probe vector pSUPV8 was used to clone promoters from Phanerochaete chrysosporium directly in Escherichia coli. Six hygromycin B-resistant recombinants were obtained and two inserted fragments of them were sequenced. The results indicated that they contain several sequences similar to eukaryotic cis regulatory elements. Only pCH6 could transform P. chrysosporium into hygromecin B resistance. PCR and dot hybridization analysis indicated that it was introduced into P. chrysosporium successfully and leaded to the HmB-resistance. The results demonstrated that HmB-resistant gene (hph) could be used as an ideal reporter gene for P. chrysosporium transformation. PMID- 11191767 TI - [Research on improving rice resistance to the pest by B.t. and SBTi genes]. AB - B.t. gene alone or and SBTi gene together were introduced into two elite indica rice varieties grown in South China by bombardment. And 21 independent transgenic lines containing B.t. gene and 4 independent transgenic lines containing B.t. gene and SBTi gene were obtained. Molecular and genetics analysis for R1 plants showed integration of multiple transgenes occurred at one genetic locus. Northern blot result proved B.t. gene expressed in R2 transgenic plants stably. Bioassays using R2 transgenic plants with leaf-folder (Cnaphalocrosis medinalis), indicated that transgenic rice plants are more resistant to the pest than untransformed control plants. And those transgenic plants containing B.t. and SBTi genes showed more resistance compared with those plants containing B.t. gene. PMID- 11191768 TI - [Direct embryogenesis from protoplast of winter wheat]. AB - Friable embryogenic calli were obtained on a modified N6 medium (NBD medium) from a winter wheat cultivar "Jinghua No. 1" (Triticum aestivum L. cv. Jinghua No. 1) and were transferred to a modified MS liquid medium (MSDL medium) to initiate embryogenic suspension cultures. Protoplasts were isolated from the suspensions and cultured on a modified MS medium (MSDP medium). The somatic embryoids were formed directly from the protoplasts and germinated into entire plants. The development of the somatic embryoids was very similar to that of zygotic embryos of wheat. PMID- 11191769 TI - [Study on gallic acid preparation by using immobilized tannase from Aspergillus niger]. AB - Immobilized tannase which had higher ability of transforming tannin from Chinese gallotannin into GA was prepared by embedding tannase with calcium alginate carrier. The immobilization conditions and some properties of the immobilized tannase were studied. The results showed that: The optimal immobilized parametres were 90 mg sodium alginate, 546 u(182 u/mL) tannase and 1%-2% CaCl2. The optimum temperature and pH value of immobilized tannase were 45 degrees C and 6.5, respectively. It was stable in the temperature range of 10-50 degrees C and between pH5-7. Based on the optimum program, the laboratory gramme-grade preparation experiments of GA were done. The average yield of GA product in three preparations was upto 61%, and was about equivalent to the yield of acidic hydrolytic method which is used to produce GA industrially now. Thus, the research results possessed potential applied value. PMID- 11191770 TI - [Photoautotrophic cultivation of Synechococcus sp. PCC7002 in photobioreactor]. AB - The Photoautotrophic cultivation of Synechococcus sp. PCC 7002 in a 15 L-airlift photobioreactor was carried out. The changes of light intensity with cell density and optical length in the cultivation system were investigated. Based on experimental results, the light attenuation could be described by I = I0exp [-( 0.0239 + 0.0777 OD750).L]. The effects of the variations of light intensity, CO2 concentration in gas inlet and culture temperature on the growth of cells during the cultivation process have also been studied. The optimized condition was determined and a high dry cell density of 3.4 g/L was obtained. The volumetric productivity reached 0.57 g/(L.d) under the optimized condition. PMID- 11191771 TI - [The ex vivo expansion of cord blood hematopoietic cells: 1. Cell growth behavior]. AB - The population growth and metabolism of hematopoietic cells from cord blood were investigated without and with hematopoietic growth factors and the long-term growth kinetics of cells was studied. In static cultivation of hematopoietic cells, the population specific growth rate was 0.34 d-1, and the average double time 2 days. The greater part of glucose was consumed and 40 mmol/L lactate was formed during cell culture. For the long-term culture, the maximum output of CFU GM appeared between the 2nd and 3rd weeks and that of BFU-E in the first week. With 50% medium exchange, the expansions of total cells, CFU-GM, and BFU-E came up to 14, 13, and 5 times, respectively. PMID- 11191772 TI - [Asymmetric biosynthesis of chiral styrene oxide]. AB - Used styrene as the sole carbon and energy source, 12 strains of aerobic bacterial and two strains of fungi were screened from a series soil samples. These strains were able to convert styrene to styrene oxide. HPLC and chiral GC method were used for determination the substrate, product and e.e value of culture broth. There were obvious effect on the biomass and epoxidase activity under various conditions in the fermentation. Styrene epoxidation of the strain PS-1206 was studied in different reaction time. 35% of conversion yield and 80% e.e value of (R)-styrene oxide could been obtained at the optimum conditions. PMID- 11191773 TI - [Metabolic calculation of the growth phase in rHSA fermentation]. AB - The model equations of the growth phase of rHSA fermentation were derived on the base of both elemental balance and metabolic balance. The unknown parameters of the model were estimated by multivariable optimization. The model can preferably describe the relations between different macroscopic reaction rates of the process and provide the key for the high-density cultivation of Pichia pastoris. PMID- 11191774 TI - [Coupling model of the substrate premeabling through the cytoplasmic membrane and Monod kinetics]. AB - Based on the analysis of the substrate permeabling through the cytoplasmic membrane, the corresponding simple transport models are proposed. By coupling of the model with the Monod kinetics, it was discovered that form of Monod kinetics doesn't change, but the kinetics parameter affected by the transport processes. This result is fit well with the literature conclusion and experimental data. PMID- 11191775 TI - [Construction and expression of coexpression plasmid of carcinoembryonic antigen and Newcastle disease virus HN gene]. AB - The eukaryotic expression plasmid (pcDNA3-CEA) containing with the gene coding for the Carcinoembryonic antigen(CEA) had been gotten with RT-PCR and gene recombination techniques. Using enzymolysis, ligation and other techniques, an eukaryotic coexpression plasmid(pcDNA3-CEA/HN) containing two expression unites of CEA and Newcastle disease virus HN gene that may have the function of immunoenhancement had been constructed. The plasmid will lay a foundation for further researching CEA nucleiotide vaccine, adjuvant and their effect of special antitumor immune. PMID- 11191776 TI - [Proliferation of attenuated infections bursal disease virus(IBDV) on Vero cell on large scale]. AB - Vero cell was selected as productive carrier in production of Attenuated IBDV. The optimal conditions in culturing IBDV in agitating bottle were figured out. After proliferation, supernatant was harvested in batch process under the condition of five-liter-agitated fermenter. The result shows it was successful to culture IBDV by this methodology. PMID- 11191777 TI - [The medium optimization of xylitol fermentation based on neural networks and genetic algorithms]. AB - Using genetic algorithms(GA) for medium optimization of xylitol fermentation, and coupling neural networks model for predicting xylitol concentration is introduced. The medium compose determined by GA is as input data of the neural networks, while the output data predicted by neural networks is as suitable value of GA for predicting. The optimum medium is further validated by experimentation. The good result, which save the experimental workload and charge, enhance the level of xylitol fermentation as well as reduced the medium consume is obtained. PMID- 11191778 TI - [Two different fermentation techniques of steriod 1,4-dehydrogenation and 11 alpha-hydroxylation]. AB - Two kinds of micro-organism, Arthrobacter sp. AX86(1,4-dehdrogenator) and Absidia sp. A28(11 alpha-hydroxylator) were used in this experiment. Two different fermentation techniques were performed to accomplish the multiple conversional reactions for producing 16 beta-methyl-11 alpha,17 alpha,21-trihydroxy-1,4 pregnadiene-3,20-dione(III) from 16 beta-methyl-3 beta,17 alpha,21-trihydroxy-5 alpha-pregnane-20-one-21-acetate(I): 1) To produce product(III) by means of a two step fermentation method which were independently performed first by Arthrobacter and next by Absiaia, and 2) the product was obtained by a sequential fermentation system of aforesaid two micro-organisms in a single fermentor without isolation of the intermediates from the mixture. Our results showed that in both fermentation systems high yield of product was obtained. However, according to the technical simplicity, shorter duration of fermentation cycle and efficient yield of product, the second method is better than the first one. PMID- 11191779 TI - Questioning validity in the area of ergonomics/human factors. AB - This paper focuses on the analysis of deviation in findings within ergonomics/human factors (E/HF) research. The current terms used to address the analysis of deviation in empirical research revolve around the notion of validity. In E/HF research papers, 'validity' is widely interpreted and includes its common parlance usage. More importantly, analysis frequently limits 'validation' to the equivalent of 'verification', eventually resulting in 'validity' as a label of little significance. To clarify the analysis of deviation, 'investigative syntaxes' are introduced to show what exactly should or can be questioned when deviation is observed, i.e. either empirical findings or propositions, and how this questioning can be structured. The possibility is discussed that, with or without the help of these syntaxes, validation may become a method of inquiry; a productive means of generating significant theoretical questions which bear directly on empirical work. PMID- 11191780 TI - Learning from errors in a driving simulation: effects on driving skill and self confidence. AB - Two experiments investigated the effect of making errors during training (error training) on a driving simulator versus learning from examples of errors (guided error training) on driving skill and confidence. Experiment 1 indicated that compared with errorless learning (where participants drove through a training run not designed to elicit errors), error training led to significantly better transfer to driving tests that were analogous to those situations encountered in training and more effective use of strategies for coping with a novel driving situation. Error training also reduced self-confidence in driving skill at the end of training relative to errorless learning. Experiment 2 provided weak evidence of the superiority of guided error training over errorless learning (where the driver in the video did not make any errors) on analogous tests, and no evidence of transfer to a novel test. Furthermore, guided error training did not influence self-confidence in driving skill. The potential value of driving simulators in providing active processing during driver training is discussed, along with the effects of passive and active exposure to errors on driver confidence. PMID- 11191781 TI - Drivers' impressions of front and rear gaps in queues. AB - Drivers' opinions on, and perception of, gaps to a leading and a following car were studied in two field experiments. In study 1, the drivers indicated their opinion on adequate, critical and legal gap to a leading and a following car at 40 and 80 km/h. The results showed that drivers indicated longer front gaps than rear gaps in all conditions. In study 2, the drivers made judgements of distance to a leading and a following car when standing still and when travelling at 80 km/h. They were also asked to manoeuvre to a position in the middle between the leader and the follower. The results in study 2 revealed a perceptual bias in the driver when travelling at 80 km/h in that the drivers were closer to the follower when they thought they were in the middle between the leader and the follower. Gaps were generally underestimated and front gap was more underestimated than rear gap. The differences between opinions on gaps in the forward and the rearward directions could, partly, be explained by a perceptual bias in the driver. The bias should have a safety-promoting effect since it makes the driver more tolerant against short rear gaps than without the bias. PMID- 11191782 TI - The 'Wheel of Misfortune': a taxonomic approach to human factors in accident investigation and analysis in aviation and other complex systems. AB - The analysis and reporting of the human factors aspects of accidents in aviation and other complex systems continues to present difficulties for investigators and analysts alike. Reason's 'latent conditions' model has had a major impact on the way accidents are conceptualized but it has proven difficult to apply as a practical tool. Recent attempts to overcome these difficulties are discussed and an alternative conceptualization is proposed. This conceptualization is based on a blend of several well-supported theoretical models in cognitive engineering and can be used to formulate a parsimonious analysis system for the investigation and reporting of the human factors aspects of accidents. Two well-known examples of transportation disasters are briefly described and related to the proposed conceptual framework. The proposed framework serves three important functions in accident investigation and analysis: a heuristic function, an investigative function, and an integrative function. PMID- 11191783 TI - Impact of fluid replacement on heat storage while wearing protective clothing. AB - This study used partitional calorimetry to determine the influence of fluid replacement on heat storage during uncompensable heat stress. Eight males performed either light (L; level treadmill walking at 0.97 m x s(-1) (3.5 km x h( 1)) or heavy (H; 1.33 m x s(-1) (4.8 km x h(-1)) at a 4% grade) exercise at 40 degrees C and 30% relative humidity while wearing nuclear, biological and chemical (NBC) protective clothing. Subjects received either no fluid (NF), or 200 or 250 ml of fluid (F) as warm water at approximately 35 degrees C immediately before and every 15 min during the L and H trials respectively. Similar reductions in heart rate were observed at both metabolic rates with F but rectal temperature responses were not different between F and NF. Tolerance time was extended during L/F (106.5 +/- 22.1 min) compared with L/NF (93.1 +/- 20.8 min) but fluid replacement had no influence during H (59.8 +/- 9.5 min and 58.3 +/- 11.1 min for F and NF respectively). Fluid replacement also had no effect on the rate of heat storage during L (108.2 +/- 20.6 W x m(-2) and 111.0 +/- 22.6 W x m(-2) for F and NF respectively) and H (172.5 +/- 11.5 W x m(-2) and 182.1 +/- 15.8 W x m(-2) for F and NF respectively). However, heat storage expressed per unit of mass was significantly increased during L/F (18.5 +/- 4.0 kJ x kg(-1) ) compared with the other trials (16.3 +/- 4.8 kJ x kg(-1), 16.6 +/- 3.0 kJ x kg( 1) and 16.7 +/- 4.0 kJ x kg(-1) for L/NF, H/F and H/NF respectively). It was concluded that fluid replacement does not alter the rate of heat storage during uncompensable heat stress but does increase the heat storage capacity during light exercise when tolerance times are > 60 min. PMID- 11191784 TI - Effects of box weight, vertical location and symmetry on lifting capacities and ratings on category scale in Japanese female workers. AB - The aim was to clarify the effects of box weight, vertical location and symmetry on the lifting capacities and subjective burden in Japanese female workers with manual material handling tasks. Sixteen healthy females were tested. They performed 12 different lifting tasks (three heights * two weights * two symmetries). It is difficult for Japanese women to exert dynamic force in lifting a 15-kg weight from the elbow to the shoulder level. A remarkable increase was observed in heart rate and category scale with ratio properties (CR-10) on large muscle group in lifting a 15-kg weight as compared with lifting a 10-kg one. Judging from calculation of the Recommended Weight Limit using the application manual by the National Institute for Occupational Safe and Health, it was also suggested that lifting the 15-kg weight from the elbow to the shoulder level was difficult for female workers. Not only peak force, but also the average upward acceleration and peak velocity were lower in asymmetric liftings than those in symmetric liftings. CR-10 for the left back and right thigh were also higher in 90 degrees right lateral plane lifting than in the mid-sagittal plane. Thus, asymmetric lifting was supposed to impose higher stress on the back contralaterally and thigh ipsilaterally to the location of the weight. PMID- 11191785 TI - Effects of training on short- and long-term skill retention in a complex multiple task environment. AB - The paper reports the results of an experiment on the performance and retention of a complex task. This was a computer-based simulation of the essential elements of a spacecraft's life support system. It allowed the authors to take a range of measures, including primary and secondary task performance, system intervention and information sampling strategies, mental model structure, and subjective operator state. The study compared the effectiveness of two methods of training, based on low level (procedure-based) and high level (system-based) understanding. Twenty-five participants were trained extensively on the task, then given a 1-h testing session. A second testing session was carried out 8 months after the first (with no intervening practice) with 17 of the original participants. While training had little effect on control performance, there were considerable effects on system management strategies, as well as in structure of operator's mental model. In the second testing session, the anticipated general performance decrement did not occur, though for complex faults there was an increase in selectivity towards the primary control task. The relevance of the findings for training and skill retention in real work environments is discussed in the context of a model of compensatory control. PMID- 11191786 TI - [Fine tuning of diagnostic procedures for gunshot wounds in the neck region]. AB - In four patients, two men aged 25, and two aged 23 and 22 years, who were admitted or came to the emergency department, a gunshot wound was found in the cervical region. Physical examination is still the key to responsible treatment in such patients--immediate surgical exploration is seldom warranted. It is important to divide the cervical region into three anatomical parts depending upon the location of the entrance wound: zone 1 is the area between clavicula and cricoid cartilage, zone 2 between cricoid cartilage and angle of the mandible, and zone 3 between the angle of the mandible and the cranial base. Zones 1 and 3 have deep vital structures which are less accessible to physical investigation or surgical exploration. This should be taken into account in deciding for additional diagnostic procedures, such as angiography. PMID- 11191787 TI - [The "best" hospitals in the Netherlands; comments on results from the Elsevier survey]. AB - Health care workers are increasingly asked to disclose the achievements and failures of their medical interventions. Comparative evaluation of hospitals seems to be inevitable. In July 2000 about 6000 health care workers in the Netherlands received a questionnaire from the general lay weekly Elsevier asking them to grade the hospitals in their area: specialists, general practitioners, heads of departments in hospitals, nursing staff and hospital directors. The questionnaire has serious methodological flaws, e.g. regarding the items included (such as 'press sensitivity' and 'waiting lists'), the way in which the score was determined (hospitals that were scored by less than 14 respondents were excluded), the way the questions were formulated (there was no way respondents could indicate their level of experience with the hospitals involved) and the very low response rate (13%). In addition there were no data to determine the accuracy of the questionnaire, the distribution of the respondents, or whether the answers had been adjusted. The questionnaire appears to be primarily aimed at creating sensation. It received little attention in the health care sector, probably because the results were contrary to the expectations. Hospital care will undoubtedly benefit from surveys applying a limited number of well-designed indicators for quality of service, but a questionable public qualification based on a competitive model such as the Elsevier questionnaire will probably do more harm than good. PMID- 11191788 TI - [Proatherogenic changes induced by hemodialysis; probably a result of bio incompatibility]. AB - Chronic haemodialysis patients have a disproportionately high risk for developing cardiovascular disease, which can only in part be explained by known risk factors such as dyslipidaemia, hypertension, hyperhomocysteinemia, diabetes mellitus and chronic volume expansion. A possible cause is that the haemodialysis treatment itself contributes to the accelerated atherosclerosis, observed in these patients. Nowadays, atherosclerosis is considered an inflammatory process, mediated by a dysfunction of the vascular endothelium. As a result, blood cells adhere to the vascular surface and release a variety of vasoactive mediators, cytokines, growth factors and free radicals. Due to the contact between blood and dialyzer, humoral systems and cellular elements are stimulated, and this may be viewed as an inflammatory reaction. As a consequence of this, the vascular surface of haemodialysis patients is repeatedly exposed to the influences of cytokines, coagulation products, vasoactive mediators, stimulated leukocytes and thrombocytes, and oxidative stress. It is therefore conceivable that the haemodialysis treatment itself enhances the greatly increased cardiovascular risk in chronic haemodialysis patients. PMID- 11191789 TI - [What is to be done with vancomycin-resistant enterococcal infections?]. AB - Recently, three epidemics in Dutch hospitals were caused by vancomycin-resistant enterococci (VRE). Although the number of infections was small, spread of colonization was extensive and many infection control measures were necessary to prevent further spread. VRE are relatively avirulent bacteria. However, few, if any, antibiotics are available for treatment of infections caused by VRE and the genetic code for resistance may be transferable to other, more virulent, bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). Although colonization and infection with MRSA have become endemic in many surrounding countries, such a situation has been prevented in the Netherlands by employing an aggressive 'search and destroy' policy. Although many questions regarding the optimal approach of VRE remain unanswered, a similar policy as employed for MRSA will not be possible. In contrast to MRSA, colonization with VRE occurs in the open population, no populations with increased risk for colonization appear to be definable and colonization cannot be eradicated. Based on common sense, a differentiated approach seems indicated in which extensive infection control measures should only be implemented when spread of a single genotype has been demonstrated. A reference laboratory should be created for uniform genotyping. PMID- 11191790 TI - [From gene to disease; from BRCA1 or BRCA2 to breast cancer]. AB - Hereditary breast cancer is a heterogeneous syndrome, both phenotypically and genetically. It affects about 5% of all breast cancer patients. The presence of ovarian cancer or breast cancer in males defines important subtypes. BRCA1 and BRCA2 are involved in all hereditary breast cancer syndromes in varying degrees. Both genes confer strongly elevated breast and ovarian cancer risks in mutation carriers, but these risks may be subject to modifying effects by other factors (genetic and/or environmental) at the individual level. In the Netherlands, DNA testing is offered under the national health insurance programme and has led to the identification of over 500 families with either a BRCA1 or BRCA2 mutation. The results of the test are being used widely by Dutch women in the decision for or against prophylactic surgery. PMID- 11191791 TI - [Diagnostic image (18). Pulmonary tuberculosis]. AB - In an 8-year-old Somali girl who had been in the Netherlands for 3 years and who was suffering from cough for 2 months, tuberculosis of the lung was diagnosed. PMID- 11191792 TI - [Psychiatric research in Southern Netherlands; most studies get completed, social scientific ones more often than pharmacotherapeutical trials]. AB - OBJECTIVE: To describe the nature and the course of scientific studies in psychiatry that have been reviewed by the Research Ethics Committee in the South Netherlands (Toetsingscommissie Zuid-Nederland (TCZ)). DESIGN: Exploratory, retrospective. METHOD: Scientific studies in psychiatry that were submitted for review in the period 1 January 1988-31 December 1998 by TCZ, were investigated to determine their progress and to find out what study features were prognostic for completion. RESULTS: In this research project 131 psychiatric studies, which were expected to be completed towards the end of 1998, were considered for inclusion. Approximately 2/3 of all studies had a social-scientific character, 1/3 being pharmacotherapeutical. 116 cases were reviewed and 114 selected. From the 88 studies started, 77 had been completed. Out of these 77 completed studies 75 have been presented and/or published. Seven patients were involved in four studies that were stopped prematurely; they were possibly incorrectly burdened. Studies described as experimental, painful, pharmacotherapeutical, externally initiated, externally financed or multicentered ran a greater risk of not being completed than studies without these characteristics. Topics such as a limited number of subjects, a large burden or a long duration also jeopardized the successful completion of a study. A multivariate analysis showed that the pharmacotherapeutical nature of studies was the most important predictor. CONCLUSION: In the psychiatric hospitals of the South Netherlands scientific research has been carried out. Many of the studies that were approved by the TCZ were started and completed. Pharmacotherapeutical research ran a greater risk of non-completion than social-scientific research. PMID- 11191793 TI - [Prevalence of lower urinary tract symptoms in men and its influence on their quality of life: Boxmeer Study]. AB - OBJECTIVE: To assess the prevalence of lower urinary tract symptoms (LUTS) in men and its influence on quality of life. DESIGN: Questionnaire investigation. METHODS: Recruitment of subjects was conducted in 1998 in the municipality of Boxmeer. Men in the age range between 40-79 years were sampled from the Municipality Basic Administration System. Data on LUTS, quality of life, and health care seeking behaviour were collected with a postal questionnaire. Severity of LUTS was evaluated with the Dutch translation of the seven items of the International Prostate Symptom Score (IPSS), to which 6 questions were added regarding micturition frequency, dribbling, difficulty to start micturition, painful micturition, decreased force of stream since the age of twenty, and how long one could wait before micturition from the moment urge was noticed. The female partners of the respondents were asked to answer the questions as well. RESULTS: 1233 men completed the questionnaire, a response of 70%. One-fifth of all participants reported moderate to severe symptoms. Dribbling, reduced force of stream and urgency appeared to be the three most prevalent symptoms. The prevalence of LUTS increased with age: 10% of men aged 40-49 reported moderate to severe symptoms (IPSS > 7) compared with 44% of men over 70. Twenty-nine per cent of the men with severe LUTS reported poor disease specific quality of life, while another 28% of these men reported excellent disease specific quality of life. All men with mild symptoms reported excellent quality of life. Nine percent of all men consulted a doctor because of LUTS, with a mean delay of 10 months. The LUTS frequencies among the female partners equalled those among the responding men. CONCLUSION: LUTS were common among men over forty and among their female partners. The prevalence increases with age. Ageing of the population may lead to increased numbers of men experiencing LUTS and to concomittant medicalization costs. It is therefore of great importance to realise that the impact of symptoms on the reported quality of life was not pronounced. PMID- 11191794 TI - [Thoracoscopic clipping of thoracic duct in a woman with persisting chylothorax]. AB - A 78-year-old female had chest pain, radiating to the back, caused by a thoracic aneurysm of the aorta. A vascular prosthesis was sutured into place through a left-sided thoracotomy. Six days after the operation she developed chylothorax on the right side. Following 14 days of conservative management, chyle leakage persisted at a rate of 1500 ml per 24 hours. By thoracoscopy the thoracic duct was dissected and clipped, which stopped the chyle leakage. The patient recovered moderately well. Conservative measures, such as adjusted nutrition, are successful in 50% of patients. Clipping of the thoracic duct by thoracoscopy is a definitive and minimally invasive procedure to treat persistent chyle leakage. PMID- 11191795 TI - [Vancomycin-resistant Enterococcus faecium outbreak in a nephrology ward]. AB - In April 2000, an outbreak of vancomycin-resistant Enterococcus faecium (VRE) was discovered in an internal medicine/nephrology and dialysis ward of the Eemland Hospital, Amersfoort, the Netherlands. Although enterococci are considered relatively non-virulent, VRE are resistant to almost all commercially available antibiotics. Surveillance cultures were obtained from all patients at the ward, all patients visiting the dialysis ward and the environment of patients. VRE were determined and clustering of strains was analysed using molecular genotyping. In all, 12 patients were colonized with the outbreak strain. Transmission of VRE usually occurs via the hands of health care workers. The ward was closed for new admissions, patients were divided in cohorts of colonized and non-colonized patients, and rooms were disinfected after patient discharge. Infection control measures (such as handwashing and use of gloves and gowns) were enforced and prescriptions of vancomycin and cephalosporins were reduced. With these measures the outbreak could be controlled. Epidemiological analysis demonstrated that earlier admission and previous use of ciprofloxacin, amoxicillin and amoxicillin clavulanic acid were risk factors for colonization. A nearby hospital was a possible source of this outbreak. PMID- 11191796 TI - [Epidemiologic increase of various genotypes of vancomycin-resistant Enterococcus faecium in a university hospital]. AB - After a report of a possible relationship between an outbreak of vancomycin resistant enterococci (VRE) in a nearby hospital and earlier admission of two of the patients with this VRE in the University Medical Centre of Utrecht (UMCU), the Netherlands, an extensive search for VRE carriers was started in the UMCU. In the study period of two months, VRE carriership was diagnosed in 51 patients in nine of the 11 wards investigated. Twenty-six patients in eight wards were colonized with the same VRE genotype as in the nearby hospital; spread was demonstrated in three wards. In addition, six patients of one ward were colonized with a second genotype and seven other patients with a third genotype, while 12 patients were carriers of a unique genotype. Most carriers were found in the internal medicine/nephrology and dialysis ward. Far-reaching measures (such as cohort nursing, admission stops, use of gowns and gloves, disinfection and restriction of use of vancomycin) taken in the four wards where spread was demonstrated, appeared effective but in three wards, spread was again demonstrated later. Frequent readmissions and transfers of patients appear to play an important part in this matter. None of the 51 colonized patients developed a serious VRE infection. PMID- 11191805 TI - Cultivation-independent techniques for studying methanotroph ecology. AB - Methane-oxidizing bacteria (methanotrophs) have attracted considerable attention over the past 30 years. They have the unique ability to use methane as sole carbon and energy source, they are found in a wide variety of environments and play a crucial role in the global methane cycle. Methanotrophs also show considerable potential for bioremediation processes such as degradation of ground water pollutants, and for production of bulk chemicals from cheap substrates. We review here the cultivation-independent molecular biological methods that are available for the detection and characterization of methanotrophs in the natural environment. PMID- 11191806 TI - Current strategies for improving food bacteria. AB - Novel concepts and methodologies are emerging that hold great promise for the directed improvement of food-related bacteria, specifically lactic acid bacteria. Also, the battle against food spoilage and pathogenic bacteria can now be fought more effectively. Here we describe recent advances in microbial physiology and genomic research of these organisms that enable novel strategies for obtaining safe, healthy, and good-tasting fermented food products. PMID- 11191807 TI - Transposon-mediated insertional mutagenesis of the D-alanyl-lipoteichoic acid (dlt) operon raises methicillin resistance in Staphylococcus aureus. AB - Two independent mutants of methicillin-resistant Staphylococcus aureus (MRSA), KAN96H1 and KAN96H2, were isolated by insertional mutagenesis with conjugative transposon Tn918. In both, the minimal inhibitory concentration (MIC) of methicillin was increased to 128 compared to 16 mg/L for the parental strain KAN96. By transduction experiments, we verified that the insertion of Tn918 conferred higher methicillin resistance on KAN96H1, but not on KAN96H2. In KAN96H1, the integration site of Tn918 was located in the 6.1-kb HindIII fragment of the KAN96 chromosomal DNA. We identified a novel D-alanyl-lipoteichoic acid (dlt) operon of S. aureus in this fragment. The amino acid sequences of four open reading frames of this operon were highly homologous to those of the dlt operon genes of Bacillus subtilis. The nucleotide sequence of the staphylococcal dlt operon is under the accession number D86240 in the DDBJ/GenBank/EMBL databases. In KAN96H1, Tn918 was inserted in the 5'-terminal region of the putative dltB gene which encoded a hypothetical membrane transporter. dlt transcripts of 4.7 kb were detected in KAN96, but were truncated to 2.3 kb in KAN96H1. No corresponding transcripts were observed in KAN96H2. Our results clearly demonstrated that defects in functions of the putative dlt operon resulted in increased methicillin resistance in MRSA. PMID- 11191808 TI - Determination of the rpoB gene sequences of Bartonella henselae and Bartonella quintana for phylogenic analysis. AB - Using the Genome Walker procedure, which allows PCR amplification of genomic DNA using a single gene-specific primer and direct automated sequencing methodology, we obtained the nucleotide sequence of the RNA polymerase beta subunit (rpoB) from Bartonella henselae and Bartonella quintana. A phylogenetic tree constructed from these data and other rpoB sequences available in GenBank is, in part, consistent with those previously derived from 16S rRNA gene sequences and confirms the position of Bartonella within the alpha subdivision of Proteobacteria. In fact, this analysis showed that rpoB data are similar to 16S rRNA data for the alpha, beta and gamma subdivisions of Proteobacteria. In contrast, concerning other bacteria included in our study, the topologies of phylogenetic trees were different. Based on the bootstrap values derived from rpoB phylogenic analysis, we believe that this molecule should contribute to better understanding the evolutionary process. PMID- 11191809 TI - Changes in external trehalase activity during human serum-induced dimorphic transition in Candida albicans. AB - Yeast-like cells (blastoconidia) of Candida albicans growing exponentially on a glucose-containing medium (YPD) exhibited low external trehalase activity and stored a negligible amount of intracellular trehalose. The addition of human serum at 37 degrees C to exponential cultures promoted a high degree of germ-tube formation with no significant changes in trehalase activity or trehalose content. In contrast, stationary cells accumulated a large amount of trehalose, while external trehalase remained at a low and practically constant level. However, resting cultures were unable to enter the dimorphic program, except when they were supplemented with fresh YPD and serum together. Only under these conditions was trehalase activated and trehalose hydrolyzed. Specific inhibition of external trehalase by validoxylamine A caused a certain delay in, and a lower level of, germ-tube formation, but did not totally block the dimorphic conversion. These results suggest that external trehalase is not involved in the serum-induced morphological transition in C. albicans. PMID- 11191810 TI - The trehalose operon of Pseudomonas fluorescens ATCC 17400. AB - The trehalose operon of Pseudomonas fluorescens ATCC 17400 consists of treP, treA and treR. The gene treP codes for a putative enzyme II subunit of the phosphotransferase system that catalyzes the phosphorylation of trehalose together with its translocation across the cell membrane and treA encodes a putative phosphotrehalase, which hydrolyzes the incoming trehalose-6-phosphate into glucose and glucose-6-phosphate. Both genes are negatively regulated by TreR, a repressor of the FadR-GntR family of transcription regulators. The operon that is induced by trehalose present in the medium shows a high similarity both in the function of genes and in the regulation with the trehalose operon of Bacillus subtilis. PMID- 11191811 TI - Identification and typing of Streptomyces strains: evaluation of interspecific, intraspecific and intraclonal differences by RAPD fingerprinting. AB - The suitability of random amplified polymorphic DNA PCR for the detection of differences between Streptomyces species and strains was evaluated. For this purpose, a protocol of RAPD specific for Streptomyces DNA, i.e. suitable for DNA presenting a high G+C content, was developed using S. ambofaciens ATCC23877. Among the 30 primers tested, all containing 80% G+C, 17 gave a pattern with this strain. Six oligonucleotides were chosen to compare 12 strains belonging to six species of Streptomyces. These oligonucleotides were then used to determine whether these strains could be differentiated at the DNA level with this method. All fingerprints obtained with six primers differed from one species to another. We showed that the RAPD method could be used to reveal intraspecific and intraclonal polymorphisms. Thus, RAPD allows for the rapid, sensitive and specific detection of genetic diversity among species and strains of Streptomyces. PMID- 11191812 TI - Genotypic characterization of enteropathogenic Escherichia coli (EPEC) isolated in Belgium from dogs and cats. AB - Enteropathogenic Escherichia coli (EPEC) are isolated from man and farm animals but also from dogs and cats. They produce typical histological lesions called 'attaching and effacing' lesions. Both plasmid and chromosomal elements are involved in the pathogenesis of EPEC infection. The presence of these genetic elements was investigated in 14 dog and three cat EPEC isolates. A bfpA-related gene was detected in five of the 17 isolates in association with high molecular weight plasmids, and a locus of enterocyte effacement (LEE) was present in all isolates. The LEE was inserted in the selC region in only 12% of the isolates. The eae, tir, espA and espB genes were analyzed by multiplex PCR. The results indicated the presence of those genes in the tested isolates with heterogeneity in the gene subtypes present: eae gamma-tir alpha-espA alpha-espB alpha (65%), eae beta-tir beta-espA beta-espB beta (29%), eae alpha-tir alpha-espA alpha-espB alpha (6%). Moreover, the espD gene was also present in dog and cat EPEC. The DEPEC and CEPEC form a heterogeneous group and five of them are closely related to human EPEC. PMID- 11191813 TI - Evidence for association of lipopolysaccharide with Pseudomonas fluorescens strain MF0 porin OprF. AB - Lipopolysaccharide (LPS) was found to be associated with the major outer membrane protein OprF of the psychrotrophic bacterium Pseudomonas fluorescens MF0, using two OprF purification procedures. OprF, purified under mild conditions, presented two types of association with LPS: tight (tLPS) and slight (sLPS), both of type R. LPS protected OprF from heat modification and trypsin degradation and facilitated the reincorporation of purified OprF into an artificial lipid bilayer without affecting its pore-forming activity. The size of the OprF channel depended on cell growth temperature, as did the extent of LPS phosphorylation: we suggest that LPS may be involved in modifications of OprF pore formation. PMID- 11191814 TI - Distribution of catabolic pathways in some hydrocarbon-degrading bacteria from a subsurface polluted soil. AB - Enrichment cultures on naphtha solvent were used to select aromatic hydrocarbon degrading bacteria from a BTEX (benzene, toluene, ethylbenzene, xylene) contaminated subsoil obtained from beneath a paint factory located in Milan, Italy. Fifteen isolated strains were studied for their different biodegradative capacities. Among these, 13 were able to grow on naphtha solvent. Ten were identified as Pseudomonas putida and three as Pseudomonas aureofaciens. Two other degraders were identified as Pseudomonas aeruginosa and Alcaligenes xylosoxidans subsp. denitrificans. Further molecular characterization of the isolates was carried out by randomly amplified polymorphic DNA analysis to ascertain that all the studied strains belonged to different haplotypes. The isolates were characterized for the presence of genes encoding for toluene dioxygenase, xylene monooxygenase and catechol 2,3-dioxygenase by polymerase chain reaction analysis and by Southern analysis. P. putida strain CM23, which showed homology with xylA,M, xylE and todC1C2BA genes, possessed multiple pathways which enabled the strain to grow on benzene, toluene and m-xylene. PMID- 11191815 TI - Carbohydrate assimilation profiles of the first Italian Candida dubliniensis clinical isolates recovered from an HIV-infected individual. AB - A total of six Candida dubliniensis isolates were obtained during 1 year of monitoring by monthly swabs from the oral cavity of an asymptomatic human immunodeficiency virus-infected individual in Catania, Italy. To the authors' knowledge, this constitutes the first recovery of C. dubliniensis from a human in Italy. Our identification procedure was based on colony color on CHROMagar Candida and carbohydrate assimilation profiles obtained by two commercial systems: API ID 32C and API 20C AUX. Karyotyping by pulsed-field gel electrophoresis confirmed the phenotypic identification. The biocodes obtained with API 20C AUX and with API ID 32C were 6172134 and 7142140015, respectively, for all six isolates. Both biocodes corresponded to those described in the literature as being produced by most C. dubliniensis isolates with each of the two identification systems. Our results confirm that both API 20C AUX and API ID 32C are able to rapidly and accurately differentiate C. dubliniensis from C. albicans. PMID- 11191816 TI - Supplement 1999 (no. 43) to the Kauffmann-White scheme. AB - This supplement reports the characterization of 26 new Salmonella serovars recognized in 1999 by the WHO Collaborating Centre for Reference and Research on Salmonella: 15 were assigned to S. enterica subsp. enterica, seven to subspecies salamae, two to subspecies diarizonae, and one to subsp. houtenae; and one to S. bongori. In addition, the antigenic factor H:z89 is described. PMID- 11191817 TI - High stakes testing: what is at stake? PMID- 11191818 TI - Deaf children creating written texts: contributions of American Sign Language and signed forms of English. AB - The objectives of this descriptive study were to investigate the ways in which American Sign Language (ASL) and English-based sign allow for comprehension of text content, and to determine how these two avenues of communication might mediate the process of reconstructing "signed meaning" in a written text. The authors argue that comprehensible input in a visual mode is possible in either ASL or English-based sign. They further claim that English-based signing may be an effective means of bridging the gap between inner speech and written text. PMID- 11191819 TI - Welcome to the real world: reflections on teaching and administration. AB - The author compares his former position as an assistant professor in a program preparing future teachers of deaf and hard of hearing students with his present position as an administrator of a public school program serving these students. He maintains that in some ways, teacher training programs in deafness and the public school settings hiring these graduates are separate worlds. The emphasis in teacher training programs appears to be on preparing graduates to work with deaf students in self-contained or residential school settings even though most teaching positions are with hard of hearing students mainstreamed in public schools. Other important areas, such as collaboration with general education teachers, litigation, parental relationships, and individualized education programs, seem to be overlooked by teacher training programs. The author employs the mockingbird metaphor from the novel To Kill A Mockingbird (Lee, 1960) to highlight differences between teacher training programs and public school settings, while making recommendations for strengthening connections between the two. PMID- 11191820 TI - Developmental practicum experiences of preservice teachers in deaf education: implications for practicum placement and faculty-student collaborative research. AB - The study examined the developmental practicum experiences of second-year graduate students in deaf education. Participants in the study consisted of a convenient sample of five practicum students. Triangulated data for the study came from the researcher's observational notes, e-mail correspondence with participants, and participants' journals. Inductive analysis was used to analyze the data. Results of the study evinced developmental experiences that are different from those reported in previous studies. The results of the study have significant implications for (a) practicum placement of graduate students in deaf education in terms of site-based orientation, use of the clinical model of supervision, opportunities for self-reflection, and periodic practicum seminars; and (b) faculty-student collaborative research in terms of planning, ethical issues, students' time needs, and training. PMID- 11191821 TI - Diversity of deaf identities. AB - Social Identity Theory (Tajfel, 1981) posits that members of minority groups achieve positive social identity by (a) attempting to gain access to the mainstream through individual mobility or (b) working with other group members to bring about social change. Some people may use a combination of both strategies. Through the use of cluster analysis, the existence of three identities associated with these strategies was discerned in a sample of 267 deaf adults: culturally hearing identity, culturally deaf identity, and bicultural identity, each comprising about a third of the sample. A subset of 56 people were interviewed in depth; excerpts are presented to illustrate the identity types. Qualified support was found for the prediction that people with culturally deaf and bicultural identities would have higher self-esteem. PMID- 11191822 TI - Results of two national surveys of leadership personnel needs in deaf education. AB - Seventy university teacher preparation programs and 100 instructional programs serving at least 120 deaf and hard of hearing students were surveyed separately to (a) determine the demand for additional doctoral-level leadership personnel in deaf education, (b) obtain guidance for university leadership preparation programs in deaf education for the purpose of recruiting leadership personnel, and (c) identify experiences that would be relevant to the positions for which prospective leadership personnel are preparing. Data representing 54% of teacher preparation programs and 65% of instructional programs serving deaf and hard of hearing students in the United States evince the need for additional doctoral level personnel for faculty positions in university teacher preparation programs in deaf education, as well as the need for leadership positions in instructional programs serving deaf and hard of hearing children. Data also provide direction for leadership preparation programs in addressing the leadership personnel needs of the field. PMID- 11191823 TI - Syntactic and semantic processing in Hebrew readers with prelingual deafness. AB - The experimenter investigated the effect of semantic clues on the reading comprehension of deaf and hearing Israeli children. Two groups of students with prelingual deafness, and a hearing control group, were asked to read syntactically simple and syntactically relative sentences of varying semantic plausibility. Sixteen of the participants who were deaf (mean grade 6.9) had been trained orally, using spoken language as their principal means of communication at home and at school. Another 16 students with deafness (mean grade 6.9), all of them children of deaf parents, had acquired sign language as their primary language. The mean grade of the hearing control group was 6.5. The results suggest that, in contrast to the case with hearing individuals, reading comprehension in individuals with prelingually acquired deafness, regardless of communication background, is predominantly determined by the semantic processing of content words, with only minor attention given to the processing of the syntactic structure of the text. PMID- 11191824 TI - Documenting English syntactic development in face-to-face signed communication. AB - The authors explored the face-to-face English competence of five students who were participating in a larger study of teachers' use of English-based signing. Using case studies, the authors report on the students' development of English based signing at the beginning and end of their involvement in this 4-year study. Grammatical forms similar in English and American Sign Language (ASL) were initially more readily produced when tested for in English, and showed consistently higher attainment levels across all the students, than grammatical forms that are different in English and ASL. The authors found emerging English forms that could be documented (a) between prompted and imitated utterances and (b) within blocks of test items examining the same grammatical constructions. The authors conclude that teachers' concerted efforts to use English-based signing as a language of instruction enhance deaf students' English acquisition. Such signing helps build a bridge between native sign language and the development of English skills necessary for literacy. PMID- 11191825 TI - Time spent viewing captions on television programs. AB - The eye movements of 23 deaf subjects, ages 14 to 61 years, were recorded 30 times per second while the subjects watched four 2.5-minute captioned television programs. The eye movement data were analyzed to determine the percentage of time each subject actually looked at the captions on the screen. It was found that subjects gazed at the captions 84% of the time, at the video picture 14% of the time, and off the video 2% of the time. Age, sex, and educational level appeared to have little influence on time spent viewing captions. When caption speed increased from the slowest speed (100 words per minute, or wpm) to the fastest speed (180 wpm), mean percentage of time spent gazing at captions increased only from 82% to 86%. A distinctive characteristic of the data was the considerable variation from subject to subject and also within subjects (from video to video) in regard to percentage of time spent gazing at captions. PMID- 11191826 TI - Transport of [3H]MPP+ in an immortalized rat brain microvessel endothelial cell line (RBE 4). AB - The aim of this study was to characterize the transport of the organic cation 1 methyl-4-phenylpyridinium (MPP+) in an immortalized cell line of rat capillary cerebral endothelial cells (RBE 4). Verapamil (100 microM) and rhodamine 123 (10 microM), and decynium22 (2 microM) and corticosterone (100 microM) reduced cellular accumulation of [3H]MPP+ applied from the luminal and abluminal cell border, respectively. When cells were grown on plastic supports, [3H]MPP+ accumulated in the cells. The kinetic parameters of the saturable component were: Km=25 microM and Vmax=246 pmol per mg protein and 15 min. A selective organic anion transport inhibitor and selective inhibitors of the L- and A-type amino acid transporters did not affect [3H]MPP+ uptake. Uptake of [3H]MPP+ was Na+ independent and metabolic energy-, pH- and potential-dependent. It was inhibited by several organic cations (e.g., verapamil, quinidine, daunomycin, dopamine) but not by others (cimetidine, tetraethylammonium, N-methylnicotinamide). In conclusion, [3H]MPP+ is efficiently transported by RBE 4 cells in both abluminal to-luminal and luminal-to-abluminal directions. Absorption of [3H]MPP+ seems to occur through a carrier-mediated mechanism belonging to the amphiphilic solute facilitator (ASF) family of transporters, but distinct from the known members of this family. PMID- 11191827 TI - Normalisation of blood pressure in hypertensive TGR(mREN2)27 rats by amlodipine vs. enalapril: effects on cardiac hypertrophy and signal transduction pathways. AB - It is still a controversial issue whether different classes of antihypertensive drugs are equally effective in the regression of cardiac hypertrophy and associated complications. The present study compared the effects of prolonged treatment with the Ca2+-channel blocker amlodipine and the ACE inhibitor enalapril, respectively, in TGR(mREN2)27 rats (TGR), an animal model of renin dependent hypertension. TGR were divided into three groups and received either amlodipine, enalapril or drinking water without addition, Sprague-Dawley rats (SPRD) served as normotensive control group. Cardiovascular parameters were monitored by radiotelemetry, and drug doses were titrated until 24-h blood pressure was reduced to approximately 140/90 mmHg in both active treatment groups. After 8 weeks of treatment left ventricular (LV) hypertrophy was completely reversed in both treatment groups despite a tenfold increase in plasma angiotensin II in amlodipine-treated TGR. In untreated TGR LV catecholamines were depleted, and beta1-adrenergic stimulation of adenylyl cyclase was blunted. Treatment of TGR with enalapril prevented both the depletion of tissue catecholamines and the desensitisation of LV beta1-adrenoceptors. Amlodipine had no effect on cardiac adrenergic signal transduction. Basal activity of LV soluble guanylyl cyclase was not different between TGR and SPRD, but its sensitivity to stimulation by nitric oxide was slightly reduced in TGR. Treatment had no effect on basal and stimulated guanylyl cyclase activity. The present study in an animal model of renin-dependent hypertension suggests that blood pressure reduction per se is sufficient for a regression of cardiac hypertrophy. However, beta adrenergic desensitisation was prevented only in the enalapril-treated group, supporting a blood pressure-independent contribution of the renin-angiotensin system to the regulation of beta-adrenergic signal transduction. PMID- 11191828 TI - Different alpha1-adrenoceptor-induced inositol phosphate formation in the two portions of rat vas deferens. AB - The two portions of rat vas deferens differed in the postjunctional sensitivity to noradrenaline. Alpha1-adrenoceptor-linked phosphoinositide breakdown was analysed in this tissue. The noradrenaline-induced [3H]inositol phosphate accumulation was similar in both ends although the pEC50 was higher in the epididymal (5.97+/-0.07) than in the prostatic (5.47+/-0.15, P<0.01) portion. [3H]Prazosin showed similar density of binding sites in both portions. Tissue pretreated with pertussis toxin did not change [3H]inositol phosphate accumulation. Finally, Western blot analysis indicated a smaller concentration of Gq/11 protein in the prostatic half (-29+/-5%, P<0.01). These results suggest that the different sensitivity to noradrenaline could be due to the higher availability of this sort of G protein in the epididymal portion. PMID- 11191829 TI - Alpha2-adrenoceptor-mediated inhibition of cultured sympathetic neurons: changes in alpha2A/D-adrenoceptor-deficient mice. AB - Alpha2-Adrenoceptor-mediated inhibition of [3H]noradrenaline release and alpha2 adrenoceptor-mediated inhibition of voltage-activated Ca2+ currents were compared in cultured thoracolumbar postganglionic sympathetic neurons from newborn wildtype (WT) mice and mice in which the alpha2A/D-adrenoceptor gene had been disrupted (alpha2A/DKO). In cultures prepared from WT mice and preincubated with [3H]noradrenaline, the alpha2-adrenoceptor agonist 5-bromo-6-(2 imidazolidinylidenamino)quinoxaline (UK 14,304) reduced the (autoinhibition-free) release of [3H]noradrenaline elicited by single electrical pulses or trains of 8 pulses at 100 Hz. The maximal inhibition by UK 14,304 amounted to 70%-85%. Its concentration-response curve was shifted to the right by phentolamine (0.3 microM) and, to a smaller extent, rauwolscine (0.3 microM). Pretreatment of the cultures with pertussis toxin abolished the effect of UK 14,304. Phentolamine and rauwolscine increased the (alpha2-autoinhibited) release of [3H]noradrenaline elicited by 18, 36 or 72 pulses at 3 Hz. In cultures from alpha2A/DKO mice, UK 14,304 failed to reduce the release of [3H]noradrenaline elicited by single pulses and phentolamine and rauwolscine failed to increase the release of [3H]noradrenaline elicited by 18-72 pulses at 3 Hz. In neurons from WT mice examined with the amphotericin B-perforated configuration of the patch clamp method, UK 14,304 reduced depolarisation-evoked Ca2+ currents. The inhibition was voltage-dependent as shown by a decline at strong depolarisation during ramp-like voltage commands and by an attenuation briefly after a conditioning depolarising pulse. The maximal inhibition by UK 14,304 was 39%. Its concentration-response curve was shifted to the right by phentolamine (0.3 microM) but not significantly changed by rauwolscine (0.3 microM) and prazosin (1 microM). Pretreatment with pertussis toxin abolished the effect of UK 14,304. In neurons from alpha2A/DKO mice, UK 14,304 also reduced depolarisation-evoked Ca2+ currents, but with a smaller maximal effect, namely 18% inhibition. Its concentration-response curve was shifted to the right by rauwolscine (0.3 microM) and prazosin (1 microM) but not significantly changed by phentolamine (0.3 microM). Pretreatment with pertussis toxin abolished the effect of UK 14,304 also in cultures from alpha2A/DKO mice. It is concluded that the only presynaptic alpha2-autoreceptors that detectably depress transmitter release from cultured thoracolumbar sympathetic neurons taken from newborn mice are alpha2A/D. In contrast, the soma dendritic alpha2-autoreceptors that inhibit voltage-gated Ca2+ channels are both alpha2A/D and non-alpha2A/D (i.e. alpha2B or alpha2c). Both presynaptic alpha2A/D and soma-dendritic alpha2A/D- and non-alpha2A/D-autoreceptors operate through pertussis toxin-sensitive G proteins in these neurons. PMID- 11191830 TI - Single-cell RT-PCR analysis of N-methyl-D-aspartate receptor subunit expression in rat locus coeruleus neurones. AB - Whole-cell patch-clamp recordings were performed on 12- to 15-day-old rat locus coeruleus neurones in a midpontine slice preparation. Application of noradrenaline (100 microM) and N-methyl-D-aspartate (NMDA; 100 microM) induced a small outward current and a distinct inward current, respectively. Single-cell reverse transcriptase-polymerase chain reaction (scRT-PCR), used to analyse the expression pattern of NMDA receptor subunits 2A, 2B, and 2C (NR2A-C) subsequent to electrophysiological characterization, demonstrated differences in the capacity of individual locus coeruleus neurones to express NR2A-C mRNA. NR2C mRNA expression predominated over those of NR2A and NR2B mRNA in most neurones. In addition, in neurones containing NR2C mRNA NMDA induced significantly larger currents than in cells lacking expression of this gene. RT-PCR studies performed on tissue preparations of adult rats also revealed a distinct expression of NR2C mRNA. In conclusion, the present data demonstrate differences in the mRNA expression pattern of NR2A-C of individual locus coeruleus neurones with a predominant NR2C mRNA expression in the majority of the cells. PMID- 11191831 TI - Fluoxetine-induced Ca2+ signals in Madin-Darby canine kidney cells. AB - The effect of fluoxetine on Ca2+ signaling in Madin-Darby canine kidney (MDCK) cells was investigated by using fura-2 as a Ca2+ probe. Fluoxetine increased [Ca2+]i concentration-dependently between 5 microM and 200 microM with an EC50 value of 40 microM. The response was reduced by external Ca2+ removal by 30%40%. In Ca2+-free medium pretreatment with 1 microM thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+ pump, abolished 100 microM fluoxetine-induced Ca2+ release. Addition of 3 mM Ca2+ to Ca2+-free medium increased [Ca2+]i when cells were pretreated with 100 microM fluoxetine. Suppression of 1,4,5-trisphosphate (IP3) formation by 2 microM U73122 (a phospholipase C inhibitor) did not affect 100 microM fluoxetine-induced Ca2+ release. Fluoxetine (5-100 microM) also increased [Ca2+]i in neutrophils, prostate cancer cells and bladder cancer cells from human and rat glioma cells. PMID- 11191832 TI - Pharmacologically elevated levels of endogenous kynurenic acid prevent nicotine induced activation of nigral dopamine neurons. AB - Previous studies have shown that systemically administered nicotine is associated with an activation of rat midbrain dopamine neurons. The aim of the present electrophysiological study was to investigate if manipulation of brain kynurenic acid, an endogenous excitatory amino acid receptor antagonist, can affect the response of nigral dopamine neurons to nicotine. A potent inhibitor of kynurenine 3-hydroxylase, PNU 156561A (40 mg/kg, i.v., 4-7 h), was utilized to increase the levels of kynurenic acid in rat brain. This treatment, which caused a fourfold increase in brain kynurenic acid levels, abolished the increase in firing rate and burst activity of nigral dopamine neurons as induced by nicotine (25-400 microg/kg, i.v.). It is proposed that the excitation of dopamine neurons in the substantia nigra following nicotine administration is an indirect effect, mediated by glutamate release. In addition, our data highlight the role of brain kynurenic acid as a potentially important modulator of basic glutamatergic responses in brain. PMID- 11191833 TI - Characterisation and comparison of novel ligands for the nociceptin/orphanin FQ receptor. AB - Studies of nociceptin/orphanin FQ (NC) have been hampered by the paucity of available ligands with activity at the nociceptin receptor (NCR). In this study we have compared the agonist profile of NC and a novel NCR agonist, Ro65-6570, in a series of radioligand binding studies and effects on forskolin-stimulated cAMP formation in Chinese hamster ovary (CHO) cells expressing the recombinant human NCR (CHOhNCR). In addition, we report the effects of three antagonists, [Nphe1]NC(1-13)NH2, J-113397 and III-BTD, on these responses. In radioligand binding studies Ro65-6570, [Nphe1]NC(1-13)NH2, J-113397 and III-BTD displaced [3H]NC with similar pKi values (8.4-8.8). This compares with a pK(D) of 10.2 for NC in a direct saturation experiment. [Nphe1]NC(1-13)NH2 and J-113397 showed at least 100-fold selectivity over classical opioid receptors. Both NC and Ro65-6570 produced a concentration-dependent inhibition of cAMP formation with pEC50 values of 9.56+/-0.06 and 8.68+/-0.04, respectively. Maximum inhibition achieved was 100%. [Nphe1]NC(1-13)NH2, J-113397 and III-BTD produced a parallel rightward shift in the concentration-response curves to both NC and Ro65-6570 with pK(B) values of approximately 6.5, approximately 7.5 and approximately 7.7, respectively. Importantly, all three antagonists were devoid of residual agonist activity. Collectively, these data indicate the value of Ro65-6570, [Nphe1]NC(1 13)NH2, J-113397 and III-BTD in studies of the physiological role played by NC. However, due to the relatively poor selectivity of Ro65-6570 and III-BTD caution should be exercised when using tissues that co-express micro-opioid receptors. PMID- 11191834 TI - A quantitative analysis of antagonism and inverse agonism at wild-type and constitutively active hamster alpha1B-adrenoceptors. AB - In order to characterize inverse agonism at alpha1B-adrenoceptors, we have compared the concentration-response relationships of several quinazoline and non quinazoline alpha1-adrenoceptor antagonists at cloned hamster wild-type (WT) alpha1B-adrenoceptors and a constitutively active mutant (CAM) thereof upon stable expression in Rat-1 fibroblasts. Receptor activation or inhibition thereof was assessed as [3H]inositol phosphate (IP) accumulation. Quinazoline (alfuzosin, doxazosin, prazosin, terazosin) and non-quinazoline alpha1-adrenoceptor antagonists (BE 2254, SB 216,469, tamsulosin) concentration-dependently inhibited phenylephrine-stimulated IP formation at both WT and CAM with Ki values similar to those previously found in radioligand binding studies. At CAM in the absence of phenylephrine, the quinazolines produced concentration-dependent inhibition of basal IP formation; the maximum inhibition was approximately 55%, and the corresponding EC50 values were slightly smaller than the Ki values. In contrast, BE 2254 produced much less inhibition of basal IP formation, SB 216,469 was close to being a neutral antagonist, and tamsulosin even weakly stimulated IP formation. The inhibitory effects of the quinazolines and BE 2254 as well as the stimulatory effect of tamsulosin were equally blocked by SB 216,469 at CAM. At WT in the absence of phenylephrine, tamsulosin did not cause significant stimulation and none of the other compounds caused significant inhibition of basal IP formation. We conclude that alpha1-adrenoceptor antagonsits with a quinazoline structure exhibit greater efficacy as inverse agonists than those without. PMID- 11191836 TI - Cannabinoid CB1 receptor-mediated inhibition of acetylcholine release in the brain of NMRI, CD-1 and C57BL/6J mice. AB - Cannabinoid CB1 receptors occur as presynaptic receptors producing inhibition of neurotransmitter release. To elucidate their physiological role, experiments on tissues from CB1 receptor knockout mice would be helpful. We studied whether CB1 receptor-mediated inhibition of acetylcholine release is detectable in the brain of NMRI mice and of CD-1 and C57BL/6J mice (the latter two strains representing the wild-type strains of the two CB1 receptor knockout mouse models). Brain slices preincubated with [3H]choline were superfused and tritium overflow was evoked electrically (3 Hz) or by introduction of Ca2+ into Ca2+-free K+-rich medium (35 mM) containing tetrodotoxin. The eletrically evoked tritium overflow from NMRI mouse hippocampal slices was inhibited (maximally by 60%) by the cannabinoid receptor agonists CP-55,940 and WIN 55,212-2 but not affected by WIN 55,212-3 (the inactive enantiomer of WIN 55,212-2; pEC50=7.9, 7.4 and <5.5). The concentration-response curve of WIN 55,212-2 was shifted to the right by the CB1 receptor antagonist SR 141716 (apparent pA2=8.6). Compared to hippocampal slices from NMRI mice, WIN 55,212-2 1 microM inhibited the electrically evoked overflow (1) from cortical slices from NMRI mice to a lesser extent and from striatal slices not at all, (2) from hippocampal slices from CD-1 and C57BL/6J mice to an identical extent and (3) from hippocampal slices from Sprague-Dawley rats to at least the same extent. SR 141716 0.32 microM abolished the effect of WIN 55,212-2 1 microM in hippocampal slices from NMRI, CD-1 and C57BL/6J mice and in cortical slices from NMRI mice. The electrically evoked tritium overflow from NMRI mouse hippocampal slices was also inhibited by the muscarinic receptor agonist oxotremorine (maximum effect of 85%; pEC50=6.5) and this effect was antagonized by the muscarinic receptor antagonist AF-DX 384 (apparent pA2=8.3). The Ca2+ evoked tritium overflow from NMRI mouse hippocampal slices was inhibited by WIN 55,212-2 in a manner sensitive to SR 141716. In conclusion, the cholinergic axon terminals of the NMRI mouse hippocampus are endowed with presynaptic CB1 receptors. Such receptors are also detectable in the hippocampus of CD-1 and C57BL/6J mice. The maximum extent of the CB1 receptor-mediated inhibition of acetylcholine release is lower than the maximum effect mediated via the autoreceptor. PMID- 11191835 TI - Apical uptake of organic cations by human intestinal Caco-2 cells: putative involvement of ASF transporters. AB - The aim of this work was to characterise the intestinal absorption of organic cations, by testing the possibility of involvement of known members of the amphiphilic solute facilitator (ASF) family in this process. For that purpose, the characteristics of the uptake of 1-methyl-4-phenylpyridinium, a model organic cation, at the brush-border membrane of Caco-2 cells were compared with those of the extraneuronal monoamine transporter (EMT)-mediated transport. Uptake of [3H]MPP+ by Caco-2 and 293hEMT cells showed pH-dependence: it was significantly reduced (to 86% and 62% of control, respectively) when the pH of the extracellular medium was decreased to 6.2, and increased (to 116% and 136% of control, respectively) when the extracellular pH was increased to 8.2. Uptake of [3H]MPP+ by Caco-2 cells and 293hEMT cells showed potential-dependence: substitution of KCl for NaCl in the incubation medium resulted in a reduction in the inward transport of [3H]MPP+ (to 70% and 40% of control, respectively). Uptake of [3H]MPP+ by Caco-2 and 293hEMT cells showed only little dependence on Na+: substitution of NaCl of the incubation media with LiCl resulted in a small decrease (of 19% and 14%, respectively) in [3H]MPP+ uptake. However, when NaCl was substituted with choline chloride, a significant reduction in [3H]MPP+ uptake by Caco-2 and 2931hEMT cells (of 56% and 68%, respectively) was observed. The effect of various compounds on initial rates of [3H]MPP+ uptake into Caco-2 and 293hEMT cells was tested. All compounds tested interacted with the specific [3H]MPP+ uptake in both cell lines. There was no correlation between the IC50s in relation to inhibition of [3H]MPP+ uptake into Caco-2 cells and into 293hEMT cells. Reverse transcriptase-polymerase chain reaction indicates that mRNA of hEMT and of the human organic cation transporter 1 (hOCT1) are present in Caco-2 cells. In conclusion, our results suggest that uptake of organic cations at the brush-border membrane of Caco-2 cells may occur through two distinct Na+ independent transporters belonging to the ASF family: hEMT and hOCT1. PMID- 11191837 TI - Modulation of noradrenaline-induced microvascular constriction by protein kinase inhibitors. AB - We have tested the role of various protein kinases in noradrenaline-induced, alpha1A-adrenoceptor-mediated constriction of mesenteric and intrarenal rat microvessels. The protein kinase C inhibitors, H7 and staurosporine, inhibited constriction in both vessel types in concentrations which also inhibit myosin light chain kinase. The more selective protein kinase C inhibitors, bisindolylmaleimide I and Go 6976, did not inhibit microvessel constriction in concentrations selective for protein kinase C. Moreover, the protein kinase C activating phorbol ester, phorbol-12-myristate-13-acetate, did not cause constriction. The tyrosine kinase inhibitors, genistein and tyrphostin 23, inhibited constriction in concentrations compatible with tyrosine kinase inhibition. An inhibitor of the extracellular signal-regulated kinase cascade, PD 98059, also caused concentration-dependent inhibition. While chelation of extracellular Ca2+ abolished noradrenaline-induced constrictions, the Ca2+-ATPase inhibitor, thapsigargin, had no effects. We conclude that tyrosine kinases and extracellular signal-regulated kinase (but not protein kinase C) may be involved in noradrenaline-induced rat mesenteric and intrarenal microvessel constriction but this appears to occur independently of an effect on sarcoplasmic Ca2+ storage. PMID- 11191838 TI - Chronic treatment with desipramine facilitates its effect on extracellular noradrenaline in the rat hippocampus: studies on the role of presynaptic alpha2 adrenoceptors. AB - Adaptive phenomena such as desensitization of autoreceptors are considered an important factor in the achievement of therapeutic efficacy of antidepressant drugs after chronic treatment. We have studied whether a chronic treatment with desipramine had a greater effect than a single dose on the extracellular concentrations of noradrenaline in the dorsal hippocampus. Administration of 10 mg/kg i.p. desipramine once daily for 14 days significantly raised the basal extracellular noradrenaline in the dorsal hippocampus 24 h but not 48 h after the last drug injection. A challenge dose of desipramine increased extracellular noradrenaline in rats treated chronically with vehicle and desipramine. The effect was significantly higher in rats treated chronically with desipramine 48 h but not 24 h after the last injection. An intraperitoneal administration of the alpha2-adrenoceptor agonist clonidine at the dose of 10 microg/kg significantly reduced extracellular noradrenaline in the control group but not in animals chronically treated with desipramine whereas 30 microg/kg clonidine produced a similar decrease in both groups. Three concentrations of clonidine (0.05, 0.5 and 1 microM) infused into the hippocampus significantly reduced extracellular noradrenaline to a similar extent in rats chronically treated with saline or desipramine. Fourty-eight hours after the last injection of the chronic treatment, [3H]RX-821002 binding to alpha2-adrenoceptors in the rat locus coeruleus measured by autoradiography was not significantly modified. A slight (17%) but significant decrease of neuronal uptake of [3H]noradrenaline was found in synaptosome preparations from dorsal hippocampus of rats chronically treated with desipramine, but this was likely due to a decrease in affinity. The results suggest that a repeated treatment with desipramine (10 mg/kg i.p. once daily for 14 days) facilitates its effect on extracellular noradrenaline in the dorsal hippocampus and induces adaptive changes probably involving desensitization of alpha2-adrenoceptors, with no changes in their density, on noradrenergic neurons in the locus coeruleus. PMID- 11191839 TI - Unravelling the pharmacological profile of the canine external carotid vasodilator '5-HT1-like' receptors: coexistence of sympatho-inhibitory 5-HT1B and postjunctional 5-HT7 receptors. AB - It has been suggested that the external carotid vasodilatation produced by serotonin (5-hydroxytryptamine; 5-HT) in anaesthetised dogs with intact vagosympathetic trunks is mediated by sympatho-inhibitory '5-HT1D' receptors and musculotropic '5-HT1-like' receptors. The present study has re-analysed this suggestion with regard to the classification schemes recently proposed by the NC IUPHAR subcommittee on 5-HT receptors. In pentobarbital-anaesthetised dogs with intact vagosympathetic trunks, 1-min intracarotid (i.c.) infusions of 5 carboxamidotryptamine (5-CT; 0.01-0.3 microg/min), 5-HT (0.3-30 microg/ min), 5 methoxytryptamine (5-MeO-T; 1-100 microg/min) or sumatriptan (1-100 microg/min) dose-dependently increased the external carotid blood flow without affecting blood pressure or heart rate. The selective 5-HT1D receptor agonist, PNU-142633 (1-1000 microg/min), was essentially inactive. After mesulergine (300 microg/kg, i.v.), an antagonist at cardiovascular 5-HT7 receptors, the above responses to 5 HT, 5-CT and 5-MeO-T were blocked, whilst those to sumatriptan remained unaffected. In contrast, after the 5-HT1B/1D receptor antagonist, GR127935 (10 microg/kg, i.v.), the responses to 5-HT, 5-CT and 5-MeO-T were not affected, but those to sumatriptan were abolished. Furthermore, after the selective 5-HT1B receptor antagonist, SB224289 (300 microg/kg, i.v.), the responses to 5-HT, 5-CT and 5-MeO-T were significantly enhanced, whereas those to sumatriptan were abolished. Interestingly, the responses to all these agonists remained unmodified after the selective 5-HT1D receptor antagonist, BRL15572 (300 microg/kg, i.v.). The above results suggest that the '5-HT1-like' receptors, which mediate canine external carotid vasodilatation, display the pharmacological profile of sympatho inhibitory 5-HT1B receptors and musculotropic 5-HT7 receptors, and confirm the existence of vasoconstrictor 5-HT1B receptors. PMID- 11191840 TI - Cloning of a chick A3 adenosine receptor: characterization of ligand binding and receptor-effector coupling of chick A1 and A3 adenosine receptors. AB - We have reported previously the cloning and partial characterization of a chick A1 adenosine receptor expressed in the heart. We report herein the cloning of a chick A3 adenosine receptor and a comprehensive characterization of both the A1 and A3 receptors expressed in human embryonic kidney 293 cells. [125I]N6-(p aminobenzyl)adenosine bound to both receptors with similar affinities and was used in competition studies. Although the selectivities of both agonists and antagonists were less than in other species, two antagonists, 3-ethyl-5-benzyl-2 methyl-6-phenyl-4-phenylethynal-(+/-)-dihydropyridine-3,5-dicarboxylate and 3,6 dichloro-2'-(isopropyloxy)-4'-methylflavone), were at least partially selective for A3 receptors while one antagonist [C8-(N-methylisopropyl)amine-N6 (5'endohydroxy)endonorboman-2-yl-9-methyladenine] was selective for A1 receptors. While both receptors coupled to the inhibition of adenylyl cyclase, we were unable to detect coupling of either receptor to phospholipase C or D. PMID- 11191841 TI - Abolition of (-)-CGP 12177-evoked cardiostimulation in double beta1/beta2 adrenoceptor knockout mice. Obligatory role of beta1-adrenoceptors for putative beta4-adrenoceptor pharmacology. AB - Some beta1- and beta2-adrenoceptor-blocking agents, such as (-)-CGP 12177, cause cardiostimulant effects at concentrations considerably higher than those that antagonise the effects of catecholamines. The cardiostimulant effects of these non-conventional partial agonists are relatively resistant to blockade by (-) propranolol and have been proposed to be mediated through putative beta4 adrenoceptors or through atypical states of either beta1- or beta2-adrenoceptors. We investigated the effects of (-)-CGP 12177 on sinoatrial rate and left atrial contractile force as well as the ventricular binding of (-)-[3H]CGP 12177 in tissues from wild-type, beta2-adrenoceptor knockout and beta1/beta2-adrenoceptor double knockout mice. The cardiostimulant effects of (-)-CGP 12177 were present in wild-type and beta2-adrenoceptor knockout mice but were absent in beta1/beta2 adrenoceptor double knockout mice. Thus, the presence of beta1-adrenoceptors is obligatory for the cardiostimulant effects of (-)-CGP 12177. It appears therefore that an atypical state of the beta1-adrenoceptor contributes to the mediation of the cardiostimulant effects induced by non-conventional partial agonists. Ventricular beta1- and beta2-adrenoceptors, labelled in wild-type with a K(D) approximately 0.5 nmol/l (approximately 16 fmol/mg protein), were absent in beta1/beta2-adrenoceptor double knockout mice. However, a high density binding site (approximately 154-391 fmol/mg protein) that did not saturate completely (K(D) approximately 80-200 nM) was labelled by (-)-[3H]CGP 12177 in the three groups of mice, being distinct from beta1- and beta2-adrenoceptors, as well as from the site mediating the agonist effects of (-)-CGP 12177. PMID- 11191842 TI - Beneficial effects of nitric oxide synthase inhibition on the recovery of neurological function after spinal cord injury in rats. AB - We have demonstrated recently that treatment with N(G)-monomethyl-L-arginine (L NMMA) accelerates electrophysiological recovery after transient spinal cord ischaemia in anaesthetized cats. To determine whether nitric oxide synthase (NOS) inhibition in the acute phase of spinal cord injury results in better functional recovery in the chronic phase, we evaluated the influence of L-NMMA on the time course of changes of neurological function and the histopathological changes after spinal cord compression in rats. Experimental spinal cord injury was produced in anaesthetized rats by short-term (5 min) compression with a thread placed around the spinal cord at T13. The recovery of motor function was assessed by a treadmill test 10, 20 and 30 days after spinal cord compression. The latency of potentials evoked by hindlimb stimulation was measured at the funiculus posterior at C1 10 days after the spinal cord injury in anaesthetized rats. Histological examinations were also performed at the same time. The compression induced spinal cord injury resulted in motor dysfunction of hindlimbs, an increase in the latency of the evoked potentials and neuronal degeneration in funiculus posterior at T13. Repeated administration of L-NMMA for 1 day significantly accelerated the recovery of the motor function, shortened the latency of the evoked potentials and attenuated the myelin vacuolization in the spinal cord. These beneficial effects of L-NMMA on neurological function and histopathological changes were abolished by coadministration of L- but not D arginine. These results suggest that NOS inhibition during the early stage of spinal cord injury has beneficial effects on the recovery of neurological function and the histopathological changes in the chronic stage. PMID- 11191843 TI - RNA secondary structure: physical and computational aspects. PMID- 11191844 TI - Thermodynamics of nucleic acids and their interactions with ligands. PMID- 11191845 TI - [Validation of biological dosimetry in patients conditioned with total body irradiation: conventional cytogenetics and in situ hybridization(FISH)]. AB - PURPOSE: Validation of biological dosimetry versus physical dosimetry in malignant haemopathy patients conditioned by total body irradiation (TBI) before bone marrow transplantation (BMT). PATIENTS AND METHODS: The scoring of chromosomal aberrations in peripheral lymphocytes irradiated in vivo was used to perform the biological dosimetry. The data were compared to those obtained with healthy volunteers' total blood exposed to in vitro irradiation with linear accelerator doses (0.2, 0.5, 0.75, 1, 2, 3, 4 and 5 Gy) for dose-response curves. In experimental animal models, can in vivo and in vitro responses be considered as being the same? All the published human data are based on retrospective dose evaluation with very large uncertainties on the dose precisely delivered to the subject. TBI before BMT was taken as a model where the dose calculation results from the physical method, with homogeneous beam and dose delivered precisely along the entire organism. In vivo response allows us to validate biological dosimetry in 15 adult patients (female + male), before (D = 0 Gy) and after the first fraction of 1.8 Gy, delivered by a linear accelerator (18 MV, dose-rate of 15.8 cGy/min-1). Two methods, conventional cytogenetics (CCG) and fluorescent in situ hybridization (FISH painting) of chromosome 4 were respectively used to analyze the unstable chromosome aberrations and stable chromosome aberrations. RESULTS: Healthy volunteer lymphocytes, before irradiation, yielded 0.1% dicentrics and 0.3% translocations of chromosome 4, with 2.5% for the whole genome. Patients before irradiation had 2% dicentrics and 11.48% chromosome 4 translocations for the whole genome. In the 15 patients, for a physical dose of 1.8 Gy, the evaluated biological dose was 1.93 Gy (95% CI: 1.85-2.05 Gy) with conventional cytogenetics and 2.06 Gy (95% CI: 1.75-2.15 Gy) with FISH. CONCLUSION: These results, in which the biologically estimated dose is in complete agreement with the dose calculated by physical dosimetry in the homogeneous irradiation model, suggest the validation of biological dosimetry in TBI conditioning. PMID- 11191846 TI - [Evaluation of late radiation-induced changes in superficial microcirculation. I. Clinical benefit of the cutaneous Doppler laser]. AB - OBJECTIVE: The changes that occur in the tissular microcirculation after therapeutic irradiation (RT) account for some of the late effects of irradiation, especially on the cutaneous level. As a rule, the methods of exploring the superficial microcirculation only measure blood flow indirectly. Only the Doppler laser can provide direct measurements of blood parameters in vivo in man. METHODS: Thirty women who had been irradiated with 45 + 20 Gy of locoregional fractionated adjuvant RT for breast cancer developed local radiation-induced fibrosis six years later (+/- 5). The local microcirculation was measured in the resting state and during thermal stimulation at 42 degrees C, using a Periflux cutaneous Doppler laser with p413 probes. Three periods of six minutes each were continuously recorded: period 1 (P1) represented basal resting cutaneous perfusion, with the slope p corresponding to the increase in perfusion when two minutes of thermal stimulation at 42 degrees C began; P2 to plateau perfusion during this stimulation; and P3 to perfusion on the return to equilibrium. Each individual was its own control. RESULTS: In the women treated by RT, the resting microcirculation in the skin underlying an area of late fibrosis rose by a factor of 2 during P1 (p < 0.001), and the P2/P1 ratio decreased by a factor of 2 (p < 0.001), compared to the control area. After thermal stimulation, there was no change in p, P2 or P3. CONCLUSION: Although a hypovascularization is frequently found in late sequelae of RT, we observed an increase of the cutaneous microcirculation associated with a maladjustment of the endothelial response to a thermal stimulation. These observations seem to reflect the presence of dilated new capillaries of the telangiectatic type, which are macroscopically undetectable. PMID- 11191847 TI - [Evaluation of late radiation-induced changes in superficial microcirculation after acute beta-irradiation. II. Prognostic importance of cutaneous Doppler laser]. AB - OBJECTIVE: The changes that occur in the tissular microcirculation after accidental acute irradiation account for some of the early effects of such irradiation, especially at the cutaneous level. The prognostic importance of the cutaneous laser doppler was tested in an experimental model of acute beta irradiation. METHODS: Ten pigs were given beta-irradiation with a high single localized dose of 90Sr/90Y (32 or 64 Gy, 7 mg/cm2) delivered to the flank, and were evaluated 2, 7, 14, 21 and 28 days thereafter. Each individual was its own control. The local microcirculation was measured in the resting state and during thermal stimulation at 42 degrees C, using a Periflux cutaneous Doppler laser with p413 probes. Three periods of six minutes each were continuously recorded: period 1 (P1) represented basal resting cutaneous perfusion, with the slope p corresponding to the increase in perfusion when two minutes of thermal stimulation at 42 degrees C began; P2 to plateau perfusion during this stimulation; and P3 to perfusion on the return to equilibrium. RESULTS: After acute beta-irradiation in the pig, all the cutaneous microcirculation parameters measured (P1, p, P2 and P3) had risen at day 2 in the irradiated area by a factor of 2 to 4, depending on the dose (p < 0.001), compared to the adjacent control area. On the other hand, as from day 7, the resting and the stimulated microcirculation varied little, except for a reduction of the slope p by a factor of 2 (p < 0.05) after the strongest radiation dose. CONCLUSION: After acute irradiation, the increase in the resting cutaneous microcirculation may correspond to immediate but transitory capillary vasodilatation that accompanies the initial erythema in accidental irradiation. The absence of vascular response to thermal stimulation seems to be a good means of reaching an early diagnosis of delayed cutaneous radiation necrosis. PMID- 11191848 TI - [Conservative treatment of extremity soft tissue sarcomas. Functional evaluation using LENT-SOMA scales and Enneking scoring]. AB - OBJECTIVE: The aim of this prospective study is the feasibility of late effects assessment by LENT-SOMA scales after conservative treatment of soft tissue sarcomas of the extremities and a comparison with the functional evaluation by the Enneking score. PATIENTS AND METHODS: During the systematic follow-up consultations, a series of 32 consecutive patients was evaluated in terms of late effects by LENT-SOMA scales and functional results by the Enneking score. The median time after treatment was 65 months. The treatment consisted of conservative surgery (all cases) followed by radiation therapy (29 cases), often combined with adjuvant therapy (12 concomitant radio-chemotherapy association cases out of 14). The assessment of the toxicity was retrospective for acute effects and prospective for the following late tissue damage: skin/subcutaneous tissues, muscles/soft tissues and peripheral nerves. RESULTS: According to the Enneking score, the global score for the overall series was high (24/30) despite four the scores zero for the psychological acceptance. According to LENT-SOMA scales, a low rate of severe sequellae (grade 3-4) was observed. The occurrence of high-grade sequellae and their functional consequences were not correlated with quality of exerese, dose of radiotherapy or use of concomitant chemotherapy. A complementarity was observed between certain factors of the Enneking score and some criteria of the LENT-SOMA scales, especially of muscles/soft tissues. CONCLUSION: The good quality of functional results was confirmed by the two mean scoring systems for late normal tissue damage. The routine use of LENT-SOMA seems to be more time consuming than the Enneking score (mean time of scoring: 13 versus five minutes). The LENT-SOMA scales are aimed at a detailed description of late toxicity and sequellae while the Enneking score provides a more global evaluation, including the psychological acceptance of treatment. The late effects assessment by the LENT-SOMA scales should be carried on in prospectives studies, especially in case of concomitant radio-chemotherapy. PMID- 11191849 TI - [Colorectal cancer in patients younger than 40 years of age]. AB - Between 1988 and 1994, 326 patients with colorectal cancers were treated at the Ibn Rochd Oncology Centre in Casablanca; 88 patients were less than 40 years old (27%). There were 79 males and nine females. A family history of colorectal cancer was noted in 5%. The most frequent symptoms were bleeding and rectal pain. The localisation of the tumour was the rectum in 70 cases. According to the anatomopathological profile, Dukes stages C and D were the most frequent and mucosal adenocarcinoma was noted in 24 cases. Seventy patients had surgery, associated with radiation therapy in 59 cases. Adjuvant chemotherapy was given in 44 cases and palliative treatment in 17 cases. Recurrence occurred in 14 cases and metastasis in other six cases. At five years, overall survival and disease free survival rates were 24% and 17%, respectively. Worse prognostic factors were mucosal adenocarcinoma, poor differentiated adenocarcinoma and Dukes C and D stages. PMID- 11191850 TI - [Conformal radiotherapy: tomotherapy]. AB - Conformal radiation therapy allows the possibility of delivering high doses at the tumor volume whilst limiting the dose to the surrounding tissues and diminishing the secondary effects. With the example of the conformal radiation therapy used at the AZ VUB (3DCRT and tomotherapy), two treatment plans of a left ethmoid carcinoma will be evaluated and discussed in detail. The treatment of ethmoid cancer is technically difficult for both radiation therapy and surgery because of the anatomic constraints and patterns of local spread. A radiation therapy is scheduled to be delivered after surgical resection of the tumor. The treatment plan for the radiation therapy was calculated on a three-dimensional (3D) treatment planning system based on virtual simulation with a beam's eye view: George Sherouse's Gratis. An effort was made to make the plan as conformal and as homogeneous as possible to deliver a dose of 66 Gy in 33 fractions at the tumor bed with a maximum dose of 56 Gy to the right optic nerve and the chiasma. To establish the clinical utility and potential advantages of tomotherapy over 3DCRT for ethmoid carcinoma, the treatment of this patient was also planned with Peacock Plan. For both treatment plans the isodose distributions and cumulative dose volume histograms (CDVH) were computed. Superimposing the CDVHs yielded similar curves for the target and an obvious improvement for organs at risk such as the chiasma, brainstem and the left eye when applying tomotherapy. These results have also been reflected in the tumor control probabilities (equal for both plans) and the normal tissue complication probabilities (NTCP), yielded significant reductions in NTCP for tomotherapy. The probability of uncomplicated tumor control was 52.7% for tomotherapy against 38.3% for 3DCRT. PMID- 11191851 TI - [Comparative dosimetry study of two methods of intensity modulation performed on the same accelerator]. AB - Intensity modulated radiation therapy (IMRT) is an advanced method of conformal radiotherapy. It permits optimal dose distribution to the target volume while preserving surrounding normal tissues. IMRT, with a multileaf collimator, can be realised in two different ways: either the segmented mode, which consists of combining small elementary static field, or the dynamic mode, which consists of moving the leaves while irradiating. The purpose of this work was to study these two methods of modulation on a Varian linear accelerator equipped with a collimator consisting of 40 pairs of one-centimetre-wide leaves. The measurements, obtained by using a diode array, showed that the quality of the irradiation in the dynamic mode does not depend on either the dose rate or the duration of the irradiation. In the segmented mode, weak magnitude segments are preferable, but increase the errors in the delivered dose. Comparisons of various profiles showed that the measured profiles are consistent with those programmed. Both modes seem to be equivalent for step-shaped profiles. In the case of profiles with constant slope, the segmentation generated by the segmented method deteriorates the profile. Even though the choice of technique is strongly dependent on the material available, the dynamic mode presents greater flexibility of use and has been chosen in our institution for IMRT. PMID- 11191852 TI - [Quality of medical records in oncology: results of an audit of the Lyon Civil Hospices]. AB - The objective of this study was to assess the quality of information contained in the medical files of patients in an oncology unit of the Lyons Civil Hospices. Prior to the audit, the health care teams established a set of consensus standards to compare with observed procedures. The analysis of the results led to propositions for guidelines designed to improve points where significant deviations were observed. In the first audit, 80 medical files from patients cared for in four oncology units were retrospectively analysed to determine information quality. Seven items of this audit were retained for a second audit on 127 medical files of patients in a cancerology unit; those items were: postal code of birth place, weight, codified evaluation of general status, TNM classification, pTNM classification, presence of pathology report, localisation of metastasis. Significant deviations were observed for pTNM classification and postal code of birth. During the second audit, a manual of procedures was distributed in the unit, and a new evaluation will be done in one year to assess the impact of guidelines. PMID- 11191853 TI - [External contour acquisition system for radiotherapy: an original solution]. AB - A contour acquisition system has been designed in radiotherapy at the Sagamie Hospital complex (Chicoutimi, Quebec) to measure the external contours of the patients who do not need a CT exam. This measuring system can produce transversal, sagittal or coronal patient contours in the treatment position. The absolute accuracy of the system is +/- 1 mm. The contours produced by this equipment can be transferred electronically or on paper to the planning system. PMID- 11191854 TI - [Male secondary breast cancer after treatment for Hodgkin's disease. Case report and review of the literature]. AB - Hodgkin's disease is now curable in more than 50% of cases, due to its chemo- and radio-sensitivity. However, treatment exposes to a risk of secondary cancer varying from 1 to 10% depending on chemoradiotherapy doses and schedules. We report a case of secondary breast cancer associated with a secondary thyroid cancer observed in a 24-year-old man treated when he was 13 years old by vinblastin and radiation for stage IIA, a Hodgkin's disease. PMID- 11191855 TI - [Radiation-induced glioblastoma and myxoma after treatment for undifferentiated carcinoma of the naspharynx]. AB - Radio-induced tumor have been known for a long time to occur after treatment of cancer during childhood. This entity is exceptional following radiotherapy of the cavum. Skull and facial osteosarcoma were described after treatment of UCNT. We report two observations of radio-induced tumors arising, respectively three and seven years after treatment of UCNT. The first one is a temporoparietal glioblastoma and the second is a rhino- and pharyngeal myxoma. The two patients are alive after treatment of the second tumor. The delay of appearance of these tumors, their situation in the field's irradiated and dose received suggests their radio-induced nature. However, the cytogenetic study is necessary to confirm the implication of radiotherapy in the genesis of these cancers. PMID- 11191856 TI - [Is tattooing still justified in breast cancer radiotherapy? Presentation of a technique that may be erased after treatment]. PMID- 11191857 TI - Ultrasound biomicroscopy in the management of Vogt-Koyanagi-Harada disease. PMID- 11191858 TI - Macular rings in Terson's syndrome. PMID- 11191859 TI - Visual field loss attributable to misting of the trial lens. PMID- 11191860 TI - Sperm factors related to in vitro penetration of porcine oocytes. AB - This study was designed to evaluate the relationship between sperm factors and penetration capacity in an in vitro system with immature porcine oocytes. The sperm parameters evaluated in 145 ejaculates were volume, sperm concentration, total cells in the ejaculate, ATP content, morpho-anomalies, percentage of motile sperm cells, forward progressive motility (FPM), acrosome status (NAR), hypo osmotic swelling test (HOS), osmotic resistance test (ORT), eosin-nigrosin viability stain and sperm membrane integrity (DCF). Porcine oocytes (a total of 8,736) were used to evaluate the capacity of the different sperm assays to predict penetration. Many parameters were found to be related to in vitro penetration ability; all conventional semen parameters, except sperm concentration and eosinnigrosin staining, were significantly better in high (>75%) than in low penetration rates (<75%). When the ejaculates were preselected the number of significantly related parameters was lower. When studying all conventional semen parameters through a stepwise multiple linear regression analysis of seminal measurements, up to 72.3% of total variance of the penetration rate could be predicted. However, as many as 4 parameters were needed (FPM in fresh semen, folded tail, NAR in post-treatment semen and DCF) for accurate prediction. On the other hand, the multiple logistic regression needed 7 parameters to discriminate 83.96% of the cases correctly. In summary, the results from the present study showed that almost all studied parameters were significantly different for predicting penetration process attained or failed, but most of them were correlated together. These findings emphasize the complexity of sperm functions and the difficulty of assessing the fertilizing ability. PMID- 11191861 TI - Vitrification and rapid-freezing of cumulus cells from rabbits and pigs. AB - To use adult somatic cloning technology in animal breeding, this technology should be complemented with nuclear donor cell cryopreservation. Two different conventional nonequilibrium methods (vitrification, V: 3.58M EG and 2.82M DMSO in PBS plus 20% FCS and rapid-freezing, RF: 0.25M sucrose, 2.25M EG and 2.25M DMSO in PBS plus 20% FCS) were assayed here on different cumuli types from rabbits and pigs. In rabbits, the cell proliferation capability of fully disaggregated cumuli was not affected by cryopreservation procedures (V: 100% and RF: 82%). Vitrified samples from partially or non-disaggregated cumuli showed the lowest proliferation frequencies (4% and 0%, respectively). In pigs, differences in cell proliferation capability were only observed between vitrified non-disagreggated cumuli and vitrified or rapid-frozen, fully disaggregated cumuli (72% vs 100% or 100%, respectively; P < 0.05). In both species, in vitro cultured sub-confluent samples were able to survive to a second cryopreservation treatment, maintaining the cell proliferation capability in nearly 50% of thawed samples. In conclusion, before cryopreservation, disaggregation of cumulus cells from both species into small clusters of cells improved their viability after thawing. These results allow us to efficiently, easily and rapidly store rabbit and pig cumulus cells, from selected high-merit females. PMID- 11191862 TI - Influence of the type of energy supply on lh secretion, follicular growth and response to estrus synchronization treatment in feed-restricted suckler beef cows. AB - The present experiment aimed to compare the efficiency of supplementation (+17.5 MJ Net Energy/d starting 47 +/- 4 days after calving) with concentrate (CS, maize grain, n = 10) or with forage (FS, maize silage, n = 10) in estrus-synchronized (Norgestomet implant 10 days inserted 60 +/- 4 days postpartum + PMSG at implant removal) beef cows previously restricted (47 MJ Net Energy/d, 785 g CP/d, 70% of requirements). The type of diet had no significant effect on basal LH concentrations (CS: 0.18 +/- 0.12 vs FS: 0.11+/- 0.02 ng/mL), LH pulse frequency (CS : 0.7 +/- 0.3 vs FS: 0.8 +/- 0.2 pulse/10 h), LH pulse amplitude (CS: 0.55 +/ 0.50 vs FS : 0.62 +/- 0.50 ng/mL) or estradiol (E2) concentrations (CS: 3.3 +/- 0.8 vs FS: 4.6+ /- 0.8 pg/mL) 13 days after the beginning of energy supplementation. No differences between CS and FS cows were observed for the number of small, medium and large follicles nor on the size of the largest follicle from 11 days before implant insertion to implant removal (IR). After IR, an LH surge was observed in 2 of the CS and 4 of the FS cows. The type of energy supplementation had no significant effect on LH (CS: 0.16 +/- 0.06 ng/mL vs FS 0.48 +/- 0.06 ng/mL; P > 0.05) or on estradiol concentrations (CS : 7.8 +/- 0.2 vs FS : 8.9 +/- 0.2 pg/mL, P > 0.10) measured hourly from 29 to 49 h after IR. Cows that ovulated after IR tended to have higher E2 concentrations than cows that did not ovulate (9.4 +/- 0.2 vs 6.3 +/- 0.2 pg/mL, P = 0.08). Similar ovulation and pregnancy rates were observed in CS and FS cows (CS: 6/10 vs FS: 7/10 and CS: 6/10 vs FS: 5/10 respectively, P > 0.05). To conclude, energy supplementation with forage was as effective as energy supplementation with concentrate to influence follicular growth, ovulation and pregnancy percentage after estrus synchronization treatment in diet-restricted beef cows. PMID- 11191863 TI - Effect of one spontaneous estrus cycle (after synchronization with PGF2alpha) on reproductive performance in dairy cows. AB - The objective of the study was to analyze the effect of a spontaneous estrus cycle after synchronization of estrus with prostaglandin F2alpha (PGF2alpha) in dairy cows on the degree of synchronization and reproductive performance. We assigned 557 Holstein cows to two treatment groups. In Group 1 estrus was synchronized by two treatments with 25 mg of Dinoprost-Trometamol in 14-day intervals. Cows were treated 27 to 33 days postpartum (dpp) and 41 to 47 dpp, respectively. Cows in Group 2 were treated with 25 mg of Dinoprost-Trometamol three times in 14-day intervals, starting at 34 to 40 dpp. The second and third injections were administered at 48 to 54 dpp and 62 to 68 dpp, respectively. All cows were inseminated on observed estrus after a voluntary waiting period of 65 days post partum. Thus cows in Group 1 were inseminated on spontaneous estrus and cows in Group 2 on induced estrus. Cows not inseminated at 80 days post partum were palpated per rectum and treated according to a predefined protocol. Herd reproductive performance measures did not differ significantly between groups. The proportion of cows with low serum progesterone levels was significantly higher 3 days after synchronization than 24 days after synchronization (97% vs 39%). The first-service conception rate was 34.8% in Group 1 and 30.7% in Group 2 (P > 0.05). Days open were 113.5 in Group 1 and 110.9 in Group 2 (P > 0.05). It is concluded that postponing artificial insemination for one spontaneous estrus cycle after synchronization decreased the degree of synchronization. This procedure, however, had no effect on herd reproductive performance compared to insemination on first observed estrus after synchronization. PMID- 11191864 TI - Sperm cryopreservation of African catfish, Clarias gariepinus: cryoprotectants, freezing rates and sperm:egg dilution ratio. AB - Methods for cryopreserving spermatozoa and optimizing sperm:egg dilution ratio in African catfish Clarias gariepinus were developed. Five percent to 25% DMSO and methanol were tested as cryoprotectants, by diluting semen in Ginzburg fish ringer and freezing in 1-milliliter cryovials in a programmable freezer. To avoid an excess of spermatozoa per egg, post-thaw semen was diluted 1:20, 1:200 or 1:2,000 before fertilization. Highest hatching rates were obtained by spermatozoa frozen in 10% methanol and post-thaw diluted to 1:200. Then, slow freezing rates (-2, -5 or -10 degrees C/min) to various endpoint temperatures (range -25 to -70 degrees C) before fast freezing in liquid nitrogen (LN2) were evaluated. Hatching rates equal to control (P > 0.05) were obtained by spermatozoa frozen at -5 degrees C/min to -45 to -50 degrees C and at -10 degrees C/min to -55 degrees C. In 3-step freezing programs, at -5 degrees C/min, the effect of holding spermatozoa for 0, 2 or 5 min at -30, -35 or -40 degrees C before fast freezing in LN2 was analyzed. Hatching rates equal to control (P > 0.05) were produced by spermatozoa frozen to, and held at, -35 degrees C for 5 min and at -40 degrees C for 2 or 5 min. Finally, frozen spermatozoa (10% methanol, -5 degrees C/min, 5 min hold at -40 degrees C, LN2, post-thaw diluted to 1:200) were tested in on farm fertilization conditions. Again, no difference (P > 0.05) in hatching rate was observed between frozen and fresh spermatozoa. Cryopreservation offers utility as a routine method of sperm storage and management for catfish. PMID- 11191865 TI - Production efficiency of Japanese black calves by transfer of bovine embryos produced in vitro. AB - The objective of this study was to examine the production efficiency of Japanese Black beef calves after transfer of bovine embryos derived from an in vitro procedure. In vitro-produced (IVP) embryos were obtained from in vitro maturation and fertilization and in vitro development by co-culture with cumulus cells until 7 or 8 days after insemination. In vivo-developed (IVD) embryos from superovulated Japanese Black heifers and cows 7 days after artificial insemination were used as a control group. Bovine embryos were transferred nonsurgically to recipient cows on Day 7 +/- 1 of the estrous cycle. Pregnancy was diagnosed by palpation per rectum at Day 60 to 70 after estrus. Pregnancy, abortion, perinatal accident and birth rates were examined according to the origin of embryos (IVP or IVD), the number of transferred embryos (single or twin) and the storage status (fresh or frozen-thawed). In Experiment 1, production efficiency by twin transfer of fresh IVP embryos was examined. Higher pregnancy rates (52 1% vs 42 9%, P < 0.05) and birth rates (47.0% vs. 33.0%, P < 0.05) were obtained by twin transfer than by single transfer of fresh IVP embryos. Thus, the twin transfer of fresh IVP embryos was effective for production of calves, although the birth rates for single and twin transfers of fresh IVD embryos were still higher (55.5% and 76.1%, P < 0.05). But the abortion and perinatal accident rates for twin transfer of fresh IVP embryos were also significantly greater than those for single and twin transfer of fresh IVD embryos (P < 0.05). In Experiment 2, production efficiency by twin transfer of frozen-thawed IVP embryos was examined. Either single or twin transfer of frozen thawed IVP embryos resulted in a similar pregnancy rate (41.3% vs. 46.7%, P > 0.05) and birth rate (34.1% vs. 41.1%, P>0.05). Thus, in combination with frozen thawed IVP embryos, the twin transfer did not enhance production efficiency. In conclusion, Japanese Black beef calves could effectively produce calves by twin transfer to Holstein recipients when using fresh IVP embryos, and by single transfer when using frozen-thawed IVP embryos. PMID- 11191866 TI - Introducing foreign DNA into tiger shrimp (Penaeus monodon) by electroporation. AB - Electroporation was used to introduce pFLAG-CMV-1-BAP, a DNA fragment that includes a bacterial alkaline phosphatase gene driven by a human cytomegalovirus (CMV) promoter, into Penaeus monodon zygotes. The transgenic tiger shrimp was achievedby using 10kV, 28 pulses, 120 g sec pulse time, 10 cycles, and a DNA concentration of 37.5 microg/mL. The hatching rate of electroporated zygotes (46%) was significantly lower than that of zygotes in the untreated group (89%). The survival rate of postlarvae in the electroporated group using a DNA concentration of 37.5 microg/mL decreased from 0.6% for postlarva 45 to 0.4% for postlarva 120. Based on dot blot analysis, the rate of gene transfer was 37% in mysis-stage, 23% postlarva 15(PL15), 19% postlarva 45(PL45), and 21% 4-month-old (about PL120). Genomic Southern blotting demonstrated that DNA from transgenic tiger shrimp contained fragments of exogenous DNA that were smaller, larger and of the same molecular size as pFLAG-CMV-1-BAP. Transferred DNA fragments were integrated into the genomes of 31% of the transgenic tiger shrimp. The exogenous DNA was mosaically distributed in a wide variety of tissues. Immunohistochemical staining revealed that the FLAG-BAP fused-protein encoded by pFLAG-CMV-1-BAP was present in the ovaries of some transgenic tiger shrimp. PMID- 11191867 TI - Estimates of heterosis for in vitro embryo production using reciprocal crosses in cattle. AB - In vitro embryo production and exploitation of heterosis are two methods of increasing productivity and accelerating genetic progress in many cattle production systems. However, it is not known if heterosis exists in bovine embryos produced in vitro. Tests for heterosis in in vitro embryo production were conducted in two experiments using reciprocal crosses. In the first, gametes from Bos taurus and Bos indicus were used; in the second, gametes from dairy and beef breeds of Bos taurus were used. In each experiment, both parental groups were used as sperm and oocyte donors, producing crossbred and purebred embryos. Oocytes obtained from abattoir-derived ovaries underwent in vitro maturation and in vitro fertilization with frozen semen. Embryos were cultured to blastocyst stage and observed. In the first experiment, higher (P < 0.05) rates of blastocyst formation were found for Bos taurus both as sires and as dams. Approximately 36% of the purebred Bos taurus oocytes and 21% of the purebred Bos indicus oocytes developed to blastocyst. Crosses averaged 16% resulting in a heterosis estimate of 45%. Ovaries from Bos indicus cows had more harvestable oocytes than did those from Bos taurus cows (P < 0.05). No evidence for heterosis was found for crosses within Bos taurus. Oocytes from beef cows had a higher rate of blastocyst formation than did those from dairy cows (30 vs. 24%, P < 0.05). These seemingly disparate results concerning heterosis were discussed in light of the period of genetic isolation of the parental populations in the two experiments. PMID- 11191868 TI - Effects of semen plasma from different fractions of individual ejaculates on IVF in pigs. AB - We applied IVM/IVF techniques to investigate effects of preincubation of sperm with different fractions of semen plasma harvested from fresh ejaculates on in vitro penetration and fertilization of in vitro matured oocytes. Three fractions of semen plasma were separated from the complete ejaculate of three Landrace boars and used to coincubate sperm obtained from the first sperm-rich fraction of the same ejaculates. After 14 to 16 h coincubation at room temperature, sperm were preincubated in capacitation medium and then inseminated into fertilization medium containing porcine oocytes matured in vitro. The semen plasma used for coincubation affected penetration rate (P < 0.001); Sperm coincubated with Fraction 1 semen plasma had a higher penetration rate compared with sperm coincubated with Fraction 2 (P < 0.05), but not with Fraction 3. Boar affected male pronucleus formation rates after insemination (P < 0.05), but no difference among boars was found in monospermy rate, average number of sperm penetrating into each fertilized oocyte, or the average number of sperm attached. No boar by fraction interaction was found for any parameters studied. PMID- 11191870 TI - Development of rabbit parthenogenetic oocytes and nuclear-transferred oocytes receiving cultured cumulus cells. AB - The present study determined a suitable parthenogenetic activation procedure for rabbit oocytes and examined the developmental potential of enucleated oocytes receiving cultured cumulus cells. Unfertilized oocytes recovered from superovulated rabbits were activated with one or two sets of electrical pulses, with or without subsequent administration of 6-dimethylaminopurine (6-DMAP). The proportion of oocytes treated with one or two sets of electrical pulses and 6 DMAP that cleaved (87% and 98%, respectively) and developed into blastocysts (77% and 85%, respectively) was significantly higher (P < 0.05) than those activated with electrical pulses alone (30% and 42% for cleavage, 7% and 17% for blastocysts). Cumulus cells separated from ovulated oocytes obtained from mature rabbits were cultured for three to five passages and then induced to quiescence by serum starvation before nuclear transfer. The enucleated oocytes receiving cumulus cells were activated with electrical pulses followed by the addition of 6 DMAP, and cultured in vitro for 5 to 6 d or transferred to pseudopregnant recipient females 1 d after activation. Of 186 nuclear-transferred oocytes, 123 (66%) cleaved and 42 (23%) developed into blastocysts. After transfer of 174 nuclear-transferred oocytes to 8 recipient females, a total of 3 implantation sites were observed in 3 recipient females but no fetuses were obtained. PMID- 11191869 TI - Ion-mediated resistance to osmotic changes of ram spermatozoa: the role of amiloride and ouabain. AB - The aim of this study was to evaluate whether the Na+/K+ and Na+/H+ exchange can maintain the function of fresh ram spermatozoa. We analyzed the quality parameters of spermatozoa from fresh ram ejaculates incubated in iso- (about 300 mOsm), hypo- (about 100 mOsm) and hyperosmotic (about 900 mOsm) media in the presence of ouabain a specific inhibitor of the Na+/K+ ATP-ase or amiloride, a specific inhibitor of the Na+/H+ antiporter. Ouabain increased the percentage of morphologically altered acrosomes in isoosmotic media (from about 10% to 15% in control to about 30% with 10(-4) M ouabain) and decreased the percentage of total motility (from about 80% in control to about 50% to 55% with 10(-4) M ouabain). Ouabain decreased the mean linearity component of motility and decreased the frequency of head displacement. The addition of ouabain increased the percentage of altered acrosomes in the hypo- and hyperosmotic media, although it did not modify viability in either media. Ouabain also increased the percentage of swollen tails in the hypoosmotic medium at higher concentrations of the inhibitor. Amiloride increased the percentage of altered acrosomes in all media although its effect was less intense than that of ouabain. In isoosmotic media, total motility was decreased from about 80% in control to about 65% with 10(-4) M amiloride. Motile spermatozoa incubated with amiloride showed a clear decrease of mean velocity and mean linearity and increased frequency of head displacement. In the hyperosmotic medium, adding amiloride decreased the percentage of viability and altered tails at concentrations as low as 10(-6) to 10(-5) M. Our results indicate that the active mechanisms which control Na+ transport play a significant role in the maintenance of function in ram spermatozoa subjected to different osmotic environments. These mechanisms may be important in maintaining ram sperm function both "in vivo" and "in vitro". PMID- 11191871 TI - Cryopreservation of spermatozoa in cyprinid fishes. AB - The present study investigated semen cryopreservation in cyprinid fish using computer-assisted sperm motility analysis for viability control. Spermatozoa of the bleak, Chalcalbumus chalcoides, were used as a basic model to describe the toxic and cryoprotective effects of internal and external cryoprotectants, their most effective concentrations and combinations, the freezing and thawing conditions, and the effects of equilibration. We also used these data to develop a cryopreservation protocol for Barbus barbus, Chondrostoma nasus, Ctenopharyngodon idella, Cyprinus cario, Hypohtalmichthys molitrix, Leuciscus cephalus, Rutilus meidingerii, and Vimba vimba. For all investigated species the optimal extender composition was a buffered physiological sperm motility inhibiting saline solution containing 10% DMSO and 0.5% glycin. The optimal sperm equilibration period in the extender was < or = 5 min. Freezing was performed in an insulated box in liquid nitrogen vapor and it was optimal at 4 to 5 cm above the surface of the liquid, depending on the species. Thawing was optimal in a 25 degrees C water bath whereby the thawing time ranged depending on species from 15 to 45 sec. This cryopreservation protocol resulted in frozen-thawed semen with 35 to 65% motile and 5 to 25% locally motile spermatozoa depending on the quality of fresh semen. PMID- 11191872 TI - Fertilizing potential in vitro of semen from young beef bulls containing a high or low percentage of sperm with a proximal droplet. AB - Fertilizing potential of semen containing a high percentage of sperm with a proximal droplet was evaluated using IVF. Design criteria: (a) specified semen with >100 x 10(6) sperm/mL with >40% progressively motile spermatozoa, after collection via electro-stimulation; (b) designated a droplet group, bulls whose semen contained >30% spermatozoa with a proximal droplet and <25% with other morphological abnormalities, and a control group, with <25% abnormalities of any type; and (c) stipulated evaluations at 11 to 13 mo of age and again -4 wk later. At the initial evaluation, when a bull was assigned to the droplet group, the next bull meeting control criteria was designated his pair; 15 pairs in four herds were studied. Semen was extended in egg-yolk citrate, cooled to 5 degrees C over approximately 2.5 h, and held at 5 degrees C. After 20 to 44 h, spermatozoa were processed by swimup, incubated with heparin, and co-cultured with oocytes (35 to 56 oocytes/sample; 18 h). Ova were observed for cleavage approximately 42 h after co-culture, and further development was evaluated on day 8. At first evaluation, cleavage rates were 18 and 46% for droplet and control groups (P < 0.01); semen had 34 to 70% and 0 to 12% droplet spermatozoa. For 10 of 15 droplet bulls, <10% of ova were cleaved whereas cleavage rate was >15% for all control bulls. At second evaluation, only three droplet bulls still had >30% of spermatozoa with a proximal droplet. Cleavage rates increased accordingly; only four droplet bulls had <10% cleaved ova and 10 had >34% cleaved ova. Three control bulls had <10% cleaved ova and nine had > or = 34% cleaved ova. Considering all 60 ejaculates, correlation between percentage of spermatozoa with a proximal droplet and percentage of cleaved ova was -0.49 (P < 0.0 1). Correlations between percentages of motile or normal spermatozoa in field evaluations and outcome in IVF were 0.28 and 0.52. Laboratory evaluations of spermatozoa concomitant with preparation for IVF revealed that only incidence of proximal droplets appeared related to outcome in IVF. We concluded: (a) semen from most yearling beef bulls with a high incidence of proximal droplet spermatozoa had severely compromised IVF fertility; (b) as these bulls matured, the incidence of proximal droplets decreased, and IVF fertilizing potential increased; and (c) semen containing >30% spermatozoa with a proximal droplet is strong evidence that fertilizing potential of the bull will be low until the incidence decreases. PMID- 11191873 TI - Expression of fibrillarin in bovine oocytes and preimplantation embryos developing in vitro. AB - Studies in somatic cells have demonstrated the participation of some defined nucleolar specific proteins in pre-rRNA synthesis and processing. Fibrillarin, a 34 kd protein localized to the dense fibrillar component of the nucleolus, is involved in the earliest cleavage step of pre-rRNA processing. Expression of fibrillarin has not been characterized during the course of bovine preimplantation development. Specific aims of this study were to characterize the expression of fibrillarin in bovine oocytes and preimplantation embryos developing in vitro. Oocytes and embryos were labeled with an anti-fibrillarin primary antibody and an FITC-conjugated goat antihuman secondary antibody and dual stained with Hoechst 33342 DNA dye. In germinal vesicle (GV) stage oocytes, obtained from 2 to 6 mm follicles, fibrillarin appeared as several large distinct fluorescent spheres within the nucleoplasm, but was not strictly localized to the nucleolus. Fibrillarin was not detected in metaphase oocytes. Expression of fibrillarin was first detected in embryos at the pronucleate stage, appearing as small spots or distinct fluorescent spheres randomly distributed within the nucleoplasm; this pattern persisted in 2- and 4-cell stage embryos. Beginning at the 8-cell stage, fibrillarin signals appeared as distinct fluorescent rings encapsulating each nucleolus. From the 16-cell through the blastocyst stage, a branching immunofluorescent pattern was observed in association with fully reticulated nucleoli. Expression of fibrillarin was absent in 8-cell, but not pronucleate stage embryos cultured with alpha-amanitin, indicating that fibrillarin is initially recruited from maternal stores in pronucleate stage embryos, but then subsequently transcribed beginning at the 8-cell stage, coincident with the onset of nucleolar, transcription. Results from this study provide further insight into the organization and development of the embryonic nucleolus during bovine preimplantation development, and may have important implications for assisted reproductive technologies, including nucleus transfer. PMID- 11191874 TI - Effects of lactation length and weaning-to-service interval on subsequent farrowing rate and litter size in Landrace and Yorkshire sows in Thailand. AB - The aim of the present study was to investigate the influence of lactation length (LL) on weaning-to-service interval (WSI), and the effect of LL and WSI on the subsequent farrowing rate and litter size among purebred Landrace and Yorkshire sows under tropical conditions. The variation in litter weight at weaning (LWW) was also studied. Data were analyzed from three purebred sow herds located in the central part of Thailand, including sows weaned during the period from January 1993 to December 1996. Data were analyzed with analysis of variance using SAS software. The procedure MIXED was used for analysis of the continuous outcome variables (namely LL, LWW, WSI, number of total born and number of live born piglets). The GLIMMIX macro was used for analysis of the categorical outcome variable, farrowing rate (FR). In the statistical analyses, WSI was grouped into 7 groups, when it was an independent variable, as follows: 1 to 4, 5, 6, 7, 8, 9, to 10, and 11 to 21 days. Lactation length was grouped into 4 groups as follows: 17 to 24, 25 to 27, 28 to 30 and 31 to 35 days. Parities were grouped into 4 groups as follows: 1, 2, 3 + 4, and 5 to 8. Landrace sows had significantly higher LWW (P < 0.001) compared with Yorkshire sows (56.1 vs. 53.6 kg). The LL was significantly (P < 0.05) shorter during the cool season than during the other seasons while no difference was found in LWW between the hot and the cool season. The LL had no effect on WSI, FR and litter sizes. The FR was significantly lower when the WSI was 7 to 10 days than when the WSI was 1 to 6 days. An increase in WSI between Days 9 to 10 and Day 21 resulted in a significant increase in FR. Subsequent litter size decreased by about 0.5 piglets when the WSI increased from 1 to 5 days to 6 to 7 days. Thereafter, litter size increased as the WSI increased from 9 to 10 days to 21 days. PMID- 11191875 TI - Effect of cysteamine during in vitro maturation on buffalo embryo development. AB - The purpose of this study was to evaluate whether the addition of cysteamine during in vitro maturation (IVM) of buffalo oocytes enhances embryo development. Cumulus-oocyte complexes (COC) from slaughterhouse ovaries were matured in vitro in TCM 199 supplemented with 10% fetal calf serum (FCS), 0.5 microg mL(-1) FSH, 5 microg mL(-1) LH, 1 microg mL(-1) 17 beta estradiol and 0 (control), 50, 100 or 200 micromol L(-1) of cysteamine for 24 hours. The matured oocytes then were fertilized and cultured for 7 days. No beneficial effect on maturation and cleavage rate was related to the addition of cysteamine. However, the percentage of embryos that developed to compact morula and blastocyst stage was significantly higher (P < or = 0.01) for oocytes matured in medium containing 50 micromol L(-1) of cysteamine than it was for oocytes matured with 0, 100 and 200 micromol L(-1) cysteamine (22.6% vs 14.9%, 15.7% and 13% respectively); moreover, the addition of 50 micromol L(-1) of cysteamine during IVM significantly (P < or = 0.01) increased the proportion of transferable quality (Grades 1 and 2) embryos (19.3% vs 11.3%, 11.6% and 11.2% respectively). The present study showed that adding a thiol compound (such as cysteamine) to the IVM medium improves buffalo in vitro embryo production (IVEP) efficiency, which so far has been unsatisfactory. PMID- 11191876 TI - Student productivity in a comprehensive care program without numeric requirements. AB - As the dental students of the Class of 2000 entered the Comprehensive Care Clinic at the University of Colorado School of Dentistry in the spring of their second year (spring of 1998), a different, competency-based set of clinical expectations was communicated to them. These students were presented a list of "Recommended Core Experiences" and told that the "requirements" for completion of the Comprehensive Care Program were 1) successful performance on all departmental competency examinations, and 2) timely completion of the comprehensive dental treatment appropriate to each assigned patient. This study examined the number of procedures completed during the six semesters in the Comprehensive Care Clinic for the Class of 2000, as compared to the clinical activity for the Class of 1999 during the same stage of their career. The overall mean number of clinical procedures performed per student was 7 percent greater for the students in the Class of 2000 than for those in the Class of 1999. These results suggest that numerical requirements are not necessary to ensure dental student productivity and that, in fact, students can complete more clinical procedures in a comprehensive care clinical environment without numerical requirements. PMID- 11191877 TI - Reasons that orthodontic faculty teach and consider leaving teaching. AB - To assess reasons why orthodontic faculty consider leaving academia, a pretested questionnaire was mailed to 200 full-time (FT) and 200 part-time (PT) faculty randomly selected from the United States and Canada. A total of 144 (72 percent) of FT and 120 (60 percent) PT responded. About 38 percent FT and 25 percent PT were currently considering leaving academia. The average age of each group was about fifty years. Although significant differences were found in fifteen factors affecting the decision to leave, three factors ranked as most important (means> or =3.4) for FTs: salary support, financial support of department, and control over work or destiny. The three factors most important (means>3. 1) for PTs were: challenge of private practice, family commitments, and personal. FT and PT were similar in the most important and least important factors influencing their initial reasons to teach and satisfaction in teaching. However, the reasons why FT considered leaving were work related, while the PT's reasons were more personal. With the current shortage of FT orthodontic faculty becoming imminently greater, it appears that work-related issues could be addressed directly by administration. PMID- 11191878 TI - Cross-sectional comparison of dental students' knowledge and attitudes before geriatric training: 1984-1999. AB - The existence of negative attitudes toward aging and a lack of factual information has been voiced in the dental and other health professions. With increasing numbers of elderly in society, intergenerational social contact is more likely to occur and has the potential to reduce negative attitudes and increase knowledge about aging. The purposes of this study were to determine if the level of intergenerational social contact of dental students in one dental school had changed over the last fifteen years and whether any such changes were related to shifts in students' baseline knowledge about aging and attitudes toward elderly patients. Dental students (n=269) representing three different cohorts were surveyed about intergenerational contact, knowledge about aging, and attitudes toward elderly patients prior to receiving any geriatric training. Overall, findings revealed little evidence of increasing intergenerational social contact, an actual decrease in knowledge, an increased negative bias in knowledge, and unchanged attitudes toward elderly patients over the past fifteen years. Recent students were more likely to have had grandparents living in the family home, to have slightly less correct factual knowledge, and to be more negatively biased in their incorrect factual knowledge than earlier students. There were no differences in attitudes toward elderly patients among cohorts. We concluded that additional research is needed to confirm or refute our trends on a national scope. Should these trends be confirmed, dental educators would be alerted to the continuing necessity of countering the students' potential negative biases as well as a lack of basic knowledge about aging. PMID- 11191879 TI - Revisiting the status of dental ethics instruction. PMID- 11191880 TI - The UCSF post-baccalaureate reapplication program: a preliminary report. AB - The University of California San Francisco School of Dentistry initiated a pilot project in 1998 to assist economically and/or educationally disadvantaged students to gain admission to dental school. Students entering the program have completed the requirements for admission to dental school, have applied, and been denied admission, and have expressed a desire to care for underserved populations. The program features a summer preparation course for the Dental Admission Test (DAT), learning skill workshops, seminars, and assistance in the reapplication process. The students participate in clinical clerkships and during the fall and spring semesters are enrolled in upper-division and graduate-level science courses at a local university. Five students participated in the pilot project in 1998; they were admitted in 1999 and have successfully completed the first year of dental school. The sixteen students enrolled in 1999 have now been admitted to one or more dental schools. Fourteen students are currently enrolled in the 2000/2001 academic year program. PMID- 11191881 TI - Catalytic efficiency determines the in-vivo efficacy of PON1 for detoxifying organophosphorus compounds. AB - Human paraoxonase (PON1) is a polymorphic, high-density lipoprotein (HDL) associated esterase that hydrolyzes the toxic metabolites of several organophosphorus (OP) insecticides and nerve agents. The activity polymorphism is determined by a Gln/Arg (Q/R) substitution at position 192. Injection of purified PON1 protects animals from OP poisoning. In the present study, we investigated the in-vivo function of PON1 for detoxifying organophosphorus insecticides in PON1-knockout mice that were challenged via dermal exposure with diazoxon, diazinon and paraoxon. PON1-knockout mice were extremely sensitive to diazoxon. Doses (2 and 4 mg/kg) that caused no cholinesterase (ChE) inhibition in wild-type mice were lethal to the knockout mice, which also showed slightly increased sensitivity to the parent compound diazinon. Surprisingly, these knockout mice did not show increased sensitivity to paraoxon. In-vitro assays indicated that the PON1R192 isoform hydrolyzed diazoxon less rapidly than did the PON1Q192 isoform. In-vivo analysis, where PON1-knockout mice received the same amount of either PON1(192) isoform via intraperitoneal (i.p.) injection 4 h prior to exposure, showed that both isoforms provided a similar degree of protection against diazoxon, while PON1R192 conferred better protection against chlorpyrifos oxon than PON1Q192. Injection of purified rabbit PON1 or either human PON1(192) isoform did not protect PONI-knockout mice from paraoxon toxicity, nor did over expression of the human PON1R192 transgene in wild-type mice. Kinetic analysis of the two human PON1(192) isoforms revealed that the catalytic efficiency (Vmax/Km) determines the in-vivo efficacy of PON1 for organophosphorus detoxication. The results indicate that PON1 plays a major role in the detoxication of diazoxon and chlorpyrifos oxon but not paraoxon. PMID- 11191882 TI - Genetic polymorphisms of biotransformation enzymes: allele frequencies in the population of the Czech Republic. AB - Polymerase chain reaction-restriction fragment length polymorphism based genotyping assays were used to determine the frequency of polymorphisms in CYP1A1 (3'-flanking region), CYP2E1 (5'-flanking region and intron 6), EPHX (exon 3 and exon 4), GSTM1 (deletion), GSTP1 (exon 5) and GSTT1 (deletion) in a group of 416 Czech individuals. A comprehensive overview of the methodology is also presented. We have found the following frequencies of mutated alleles: CYP1A1-m2, 0.097; CYP2E1-C, 0.077; CYP2E1-c2, 0.023; EPHX(exon 3)-His, 0.381; EPHX(exon 4)-Arg, 0.198; GSTM1-null, 0.51; GSTP1-Val, 0.3; GSTT1-null, 0.164. These values are similar to those presented in the majority of studies on European Caucasians, although a few cases of significant differences in the distribution of genotypes were found. These differences were most probably caused by methodological variations or statistical bias in the analyses of low numbers of samples in the control groups of some authors. Based on the results of EPHX genotyping, the activity of its protein product was deduced and the Czech population was divided into three subgroups with low, medium and high EPHX activity. We found that 43% of the Czech population would fall into the low, 44% into the medium and 13% into the high EPHX activity group. The data obtained may prove to be very useful for epidemiological studies on the influence of genetic polymorphisms of biotransformation enzymes on carcinogenesis or other environment-related diseases. PMID- 11191883 TI - Relationship of phenol sulfotransferase activity (SULT1A1) genotype to sulfotransferase phenotype in platelet cytosol. AB - Sulfation catalysed by human cytosolic sulfotransferases is generally considered to be a detoxification mechanism. Recently, it has been demonstrated that sulfation of heterocyclic aromatic amines by human phenol sulfotransferase (SULT1A1) can result in a DNA binding species. Therefore, sulfation capacity has the potential to influence chemical carcinogenesis in humans. To date, one genetic polymorphism (Arg213His) has been identified that is associated with reduced platelet sulfotransferase activity. In this study, data on age, race, gender, SULT1A1 genotype and platelet SULT1A1 activity were available for 279 individuals. A simple colorimetric phenotyping assay, in conjunction with genotyping, was employed to demonstrate a significant correlation (r = 0.23, P < 0.01) of SULT1A1 genotype and platelet sulfotransferase activity towards 2 naphthol, a marker substrate for this enzyme. There was also a difference in mean sulfotransferase activity based on gender (1.28 nmol/min/mg, females; 0.94 nmol/min/mg, males, P = 0.001). DNA binding studies using recombinant SULT1A1*1 and SULT1A1*2 revealed that SULT1A1*1 catalysed N-hydroxy-aminobiphenyl (N-OH ABP) DNA adduct formation with substantially greater efficiency (5.4 versus 0.4 pmol bound/mg DNA/20 min) than the SULT1A1*2 variant. A similar pattern was observed with 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5b]pyridine (N-OH-PhIP) (4.6 versus 1.8 pmol bound/mg DNA/20 min). PMID- 11191884 TI - Compound heterozygosity for missense mutations in the flavin-containing monooxygenase 3 (FM03) gene in patients with fish-odour syndrome. AB - Fish-odour syndrome is a highly unpleasant disorder of hepatic trimethylamine (TMA) metabolism characterized by a body odour reminiscent of rotting fish, due to excessive excretion of the malodorous free amine. Although fish-odour syndrome may exhibit as sequelae with other conditions (e.g. liver dysfunction), many patients exhibit an inherited, more persistent form of the disease. Ordinarily, dietary-derived TMA is oxidized to the nonodorous N-oxide by hepatic flavin containing monooxygenase 3 (FMO3). Our previous demonstration that a mutation, P153L (C to T), in the FMO3 gene segregated with the disorder and inactivated the enzyme confirmed that defects in FMO3 underlie the inherited form of fish-odour syndrome. We have investigated the genetic basis of the disorder in two further affected pedigrees and report that the three propositi are all compound heterozygotes for causative mutations of FMO3. Two of these individuals possess the P153L (C to T) mutation and a novel mutation, N61S (A to G). The third is heterozygous for novel, M4341 (G to A), and previously reported, R492W (C to T), mutations. Functional characterization of the S61, 1434 and W492 variants, via baculovirus-mediated expression in insect cells, confirmed that all three mutations either abolished, or severely attenuated, the capacity of the enzyme to catalyse TMA N-oxidation. Although 1434 and W492 were also incapable of catalysing the S-oxidation of methimazole, S61 was fully active with this sulphur containing substrate. Since an asparagine is conserved at the equivalent position to N61 of FMO3 in mammalian, yeast and Caenorhabditis elegans FMOs, the characterization of the naturally occurring N61S (A to G) mutation may have identified this asparagine as playing a critical role specifically in FMO catalysed N-oxidation. PMID- 11191885 TI - Tissue specific differences in the regulation of the UDP glucuronosyltransferase 2B17 gene promoter. AB - The human UDP glucuronosyltransferase UGT2B17, glucuronidates androgens and is expressed in the liver and the prostate. Although evidence suggests that variations in UGT2B17 expression between tissues may be a critical determinant of androgen response, the factors that regulate UGT2B17 expression in the liver and prostate are unknown. In this study, we have isolated a 596 bp promoter of the UGT2B17 gene and studied its regulation in the liver cell line, HepG2 and the prostate cell line, LNCaP. The transcription start site of UGT2B17 was mapped and proteins that bound to the proximal promoter were detected by DNase1 footprint analysis. A region (-40 to -52 bp) which resembled a hepatocyte nuclear factor 1 (HNF1) binding site bound proteins in nuclear extracts from HepG2 cells, but did not bind proteins from LNCaP nuclear extracts. In HepG2 cells, HNF1alpha bound to this region and activated the UGT2B17 promoter, as assessed by functional and gel shift assays. HNF1alpha activation of the promoter was prevented by mutation or deletion of the putative HNF1 site. The related transcription factor HNF1beta, which is present in HepG2 cells, did not activate the promoter. The UGT2B17 promoter could also be activated by exogenous HNF1alpha in LNCaP cells. However, because these cells do not contain HNF1alpha, other transcription factors must regulate the UGT2B17 promoter. Cotransfection experiments showed that HNF1beta, elevates promoter activity in LNCaP cells. This activation did not involve the putative HNF1 region (-40 to -52 bp) since mutation of this region did not affect promoter activation by HNF1beta. These results suggest that the UGT2B17 promoter is regulated by different factors in liver-derived HepG2 and prostate-derived LNCaP cells. PMID- 11191886 TI - Prospective evaluation of detoxification pathways as markers of cutaneous adverse reactions to sulphonamides in AIDS. AB - The use of sulphonamides is complicated by a high rate of cutaneous reactions in AIDS. Metabolic risk factors have been suspected for these reactions. We conducted a prospective study to evaluate whether glutathione S-transferase M1 null genotype, glutathione deficiency and acetylator status as risk factors. To explain the high frequency of slow acetylator phenotype in AIDS patients, we compared N-acetyltransferase-2 phenotype and genotype in this population. AIDS patients treated with sulphonamides for Pneumocystis carinii pneumonia or toxoplasmosis were followed up for cutaneous reactions. Glutathione S-transferase genotyping, glutathione level determination, N-acetyltransferase-2 genotyping and phenotyping were performed. One hundred and thirty-six AIDS patients were studied. Glutathione S-transferase M1 and T1 null genotypes, intracellular glutathione level, slow acetylator genotype and phenotype were not risk factors for cutaneous sulphonamides reactions. The association of glutathione S transferase M1 null genotype and the slow acetylator one was a risk factor [Fisher's exact test, odds ratio (OR) = 2.6, 95% confidence interval (CI) = 1.2 5.9; P = 0.02]. A discordance between acetylator genotype and phenotype was found in 35% of patients. This frequency was significantly higher than the 6-7% expected (Fisher's exact test: OR = 7.5, 95% CI = 4.2-13.4; P < 0.0001). Suspected metabolic risk factors for sulphonamides cutaneous reactions were not confirmed prospectively. However, the association of glutathione S-transferase M1 null genotype and the slow acetylator one appeared to increase the risk of reactions. We clearly showed that the acetylation phenotype measured by caffeine probe could be modified by the disease. PMID- 11191887 TI - Distribution of the N-oxidation of dietary-derived trimethylamine in a male Chinese population. PMID- 11191888 TI - Presidential address. Global change and emerging infectious diseases. PMID- 11191889 TI - Introduction of Dr. David S. Lindsay as the recipient of the Henry Baldwin Ward medal for 2000. PMID- 11191890 TI - Acceptance of the 2000 Henry Baldwin Ward medal. PMID- 11191891 TI - Characterization of proteases in the skin mucus of Atlantic salmon (Salmo salar) infected with the salmon louse (Lepeophtheirus salmonis) and in whole-body louse homogenate. AB - As part of an investigation of the biochemical interactions between the salmon louse Lepeophtheirus salmonis and Atlantic salmon Salmo salar, we characterized protease activity in the skin mucus of noninfected Atlantic salmon and Atlantic salmon infected with L. salmonis and in an L. salmonis whole-body homogenate. Zymography revealed that mucus from infected salmon contained a series of low molecular-mass (17-22 kDa) serine proteases that were not present in the mucus of noninfected salmon. Based on molecular mass, inhibition studies, and affinity chromatography, the series of proteases was identified as being trypsin-like. Similar proteases were observed in the L. salmonis homogenate and in mucus from noninfected Atlantic salmon following a 1-hr incubation with live L. salmonis. An antibody raised against Atlantic salmon trypsin failed to recognize any proteases in the mucus of noninfected salmon or infected salmon or in the L. salmonis homogenate. Collectively, these findings suggest that the trypsin-like proteases present in the mucus of infected Atlantic salmon were produced by L. salmonis, possibly to aid in feeding and evasion of host immune responses. PMID- 11191892 TI - Glycogenin-dependent organization of Ascaris suum muscle glycogen. AB - In Ascaris suum, muscle glycogen is synthesized during host feeding intervals and degraded during nonfeeding intervals. Glycogen accumulation is up to 12-fold greater than that observed in mammalian muscle. Previous studies have established that many aspects of the parasite glycogen metabolism are comparable with the host, but a novel form of glycogen synthase designated GSII also occurs in the parasite. In this report glycogenin has been identified as the core protein in both mature glycogen and the GSII complex. Digestion of GSII complex glycogen generates discreet intermediates that may correspond to a proglycogen pool, whereas digestion of mature glycogen does not generate these intermediates. Because both GSII complex glycogen and mature glycogen serve as GSII substrates, the GSII complex likely represents an intermediate between glycogenin and mature glycogen. The regulation of glycogenin synthesis or the regulation of GSII activity that converts glycogenin to proglycogen, or both, may account for high levels of polysaccharide accumulation that are essential for A. suum survival. PMID- 11191893 TI - Differentiation of Trypanosoma cruzi epimastigotes: metacyclogenesis and adhesion to substrate are triggered by nutritional stress. AB - Differentiation of Trypanosoma cruzi epimastigotes to metacyclic trypomastigotes occurs in the insect rectum, after adhesion of the epimastigotes to the intestinal wall. We investigated the effect of the nutritional stress on the metacyclogenesis process in vitro by incubating epimastigotes in the chemically defined TAU3AAG medium supplemented with different nutrients. Addition of fetal bovine serum induced epimastigote growth but inhibited metacyclogenesis. In this medium, few parasites attached to the substrate. Ultrastructural analysis demonstrated reservosomes at the posterior end of the epimastigotes. Incubation of the cells in TAU3AAG medium containing gold-labeled transferrin resulted in high endocytosis of the marker by both adhered and free-swimming epimastigotes. No intracellular gold particles could be detected in trypomastigotes. Addition of transferrin gold complexes to adhered epimastigotes cultivated for 4 days in TAU3AAG medium resulted in decrease of both metacyclogenesis and adhesion to the substrate, as compared with parasites maintained in transferrin-free medium. Adhesion to the substrate is triggered by nutritional stress, and proteins accumulated in reservosomes are used as energy source during the differentiation. A close relationship exists among nutritional stress, endocytosis of nutrients, adhesion to the substrate, and cell differentiation in T. cruzi epimastigotes. PMID- 11191894 TI - A new species of Swingleus (Monogenea: Gyrodactylidae) from the mummichog Fundulus heteroclitus, in the Delaware Bay. AB - Swingleus ancistrus n. sp. (Monogenea: Gyrodactylidae) is described from the skin and fins of Fundulus heteroclitus from Canary Creek Marsh, Lewes, Delaware. Subsequent records from New Jersey, Maryland, Virginia, and North Carolina are reported. Swingleus ancistrus is differentiated from S. polyclithroides, the only other species of the genus, primarily by its size, haptoral morphology, host, and locality. Swingleus ancistrus is larger in almost every dimension and exhibits a distinct notch on the anterior border of the opisthaptor, and several features of the haptoral anatomy and peduncular bar are unique. The prevalence of infection in hosts collected from the type locality in August was 100%. The maximum number of S. ancistrus recovered from a single host was 134. The average intensity of infection was 24 S. ancistrus per host from the type locality. PMID- 11191895 TI - A comparative study of mammalian and reptilian alternative pathway of complement mediated killing of the Lyme disease spirochete (Borrelia burgdorferi). AB - The potential bactericidal activity of the alternative complement pathway of mammalian and reptilian sera to Borrelia burgdorferi sensu stricto (s.s.) was evaluated in vitro. Complement-mediated killing was observed when cultured spirochetes were inoculated into sera from the western fence lizard (Sceloporus occidentalis) and from the southern alligator lizard (Elgaria multicarinata), but not when they were inoculated into serum from either the deer mouse (Peromyscus maniculatus) or from humans. Spirochetes were still alive after 4 hr in lizard serum that had been preheated at 56 C for 30 min to inactivate complement. Furthermore, when lizard serum was chelated with 10 mM ethylenediaminetetraacetic acid to block all complement activation, borreliacidal activity was arrested. When lizard serum was chelated with 10 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid plus 4 mM MgCl2 to block only classical complement pathway activation, >85% of spirochetes were immobilized within 1 hr. Differences in B. burgdorferi s.s. mortality were not observed when chelators with or without MgCl2 were added to serum from either deer mice or humans. Proteins comprising the alternative complement pathway are responsible for the borreliacidal activity observed in the blood of S. occidentalis and E. multicarinata. PMID- 11191896 TI - Huffmanela mexicana n. sp. (Nematoda: Trichosomoididae) from the marine fish Sphoeroides annulatus in Mexico. AB - A new species of trichosomoidid nematodes, Huffmanela mexicana n. sp., is established on the basis of its egg morphology and biological characters. The dark-shelled, embryonated eggs of this histozoic parasite occur in masses in the inner layer of the swimbladder wall of the bullseye puffer fish Sphoeroides annulatus Jenyns, 1843 (Tetraodontidae, Tetraodontiformes) off the Pacific coast of Mexico (Sinaloa State) and are characterized mainly by their shape and size (63-69 x 30-33 microm), an aspinose surface, relatively small polar plugs, and their thick egg wall (4-5 microm). A key to Huffmanela species based on egg morphology is presented. PMID- 11191898 TI - Argentophilic structures of the miracidia and cercariae of Philophthalmus distomatosa n. comb. from Israel. AB - The morphology and patterns of distribution of the argentophilic structures of miracidia and cercariae of Philophthalmus distomatosa n. comb. are described. The epidermal plate arrangement of the vast majority (94.2%) of miracidia studied conformed to the formula 6:8:4:2 = 20. The rest (5.8%) displayed the following patterns of arrangement of epidermal plates: 6:7:4:2 = 19; 6:6:4:2 = 18; and 6:4:4:2 = 16. Twenty papillalike structures were observed on the terebratorium. They were arranged along 1 axis, in 3 groups. Most commonly, 16 papillae were present on the body, located between epidermal plates of the first and second rows. The eye spots were located dorsally, near interepidermal space S1. The numbers, arrangements, and locations of the excretory pores varied. Patterns of distribution of the tegumentary papillae of P. distomatosa n. comb. cercariae are given, including those of the cephalic regions, periacetabular region, and tail. Argentophilic structures of the mentioned larval stages and of other parameters clearly distinguishing between the presently described species and those of P. lucipetus from Israel are summarized. On the basis of comparison of the presently described larval stages and those of other Melanoides tuberculata-associated larval stages of Philophthalmus in Israel and Jordan, the possibility exists that a third species occurs in Israel. PMID- 11191897 TI - Complement-mediated killing of Borrelia burgdorferi by nonimmune sera from sika deer. AB - Various species of cervid deer are the preferred hosts for adult, black-legged ticks (Ixodes scapularis and Ixodes pacificus) in the United States. Although frequently exposed to the agent of Lyme disease (Borrelia burgdorferi), these animals, for the most part, are incompetent as transmission reservoirs. We examined the borreliacidal activity of normal and B. burgdorferi-immune sera from sika deer (Cervus nippon) maintained in a laboratory setting and compared it to that of similar sera from reservoir-competent mice and rabbits. All normal deer sera (NDS) tested killed > 90% of B. burgdorferi cells. In contrast, normal mouse and rabbit sera killed < or = 22% of the Borrelia. Anti-B. burgdorferi antibodies could not be detected in any normal sera by indirect fluorescent antibody assay (IFA). Sera collected from deer 6 wk after exposure to B. burgdorferi by tick feeding exhibited IFA titers of 1:256, whereas sera from mice and rabbits similarly exposed had titers of > 1:1,024. Heat treatment (56 C, 30 min) of NDS reduced borreliacidal activity, with < 20% of the B. burgdorferi cells killed, suggesting complement-mediated killing. The chelators EGTA and EDTA were used to block the classical or both the classical and alternative complement pathways, respectively. Addition of 10 mM EGTA to NDS had a negligible effect on borreliacidal activity, with > 90% of the cells killed. Addition of 10 mM EDTA reduced the killing to approximately 30%, whereas the addition of Mg2+ (10 mM) restored borreliacidal activity to NDS. The addition of zymosan A, an activator of the alternative pathway, increased the survival of B. burgdorferi cells to approximately 80% in NDS. These data suggest that the alternative complement activation pathway plays a major role in the borreliacidal activity of NDS. Additionally, 10 mM EGTA had almost no effect on the killing activity of B. burgdorferi-exposed deer sera, suggesting that the classical pathway is not involved in Borrelia killing, even in sera from B. burgdorferi-exposed deer. PMID- 11191899 TI - Morphologic, host specificity, and genetic characterization of a European Cryptosporidium andersoni isolate. AB - This study was undertaken in order to characterize a Cryptosporidium muris-like parasite isolated from cattle in Hungary and to compare this strain with other Cryptosporidium species. To date, the large-type oocysts isolated from cattle were considered as C. muris described from several mammals. The size, form, and structure of the oocysts of the Hungarian strain were identical with those described by others from cattle. An apparent difference between the morphometric data of C. muris-like parasites isolated from cattle or other mammals was noted, which is similar in magnitude to the differences between Cryptosporidium meleagridis and Cryptosporidium felis or between Cryptosporidium serpentis and Cryptosporidium baileyi. The cross-transmission experiments confirmed the findings of others, as C. muris-like oocysts isolated from cattle fail to infect other mammals. The sequence of the variable region of small subunit (SSU) rRNA gene of the strain was 100% identical with that of the U.S. Cryptosporidium andersoni and C. andersoni-like isolates from cattle. The difference between the SSU rRNA sequence of bovine strains and C. muris is similar in magnitude to the differences between C. meleagridis and Cryptosporidium parvum anthroponotic genotype or between Cryptosporidium wrairi and C. parvum zoonotic genotype. Our findings confirm that the Cryptosporidium species responsible for abomasal cryptosporidiosis and economic losses in the cattle industry should be considered a distinct species, C. andersoni Lindsay, Upton, Owens, Morgan, Mead, and Blagburn, 2000. PMID- 11191900 TI - Intraspecific heterogeneity in the mini-exon gene localization of Leishmania (Viannia) panamensis and Leishmania (Viannia) guyanensis from Colombia. AB - Intraspecific heterogeneity was demonstrated in the mini-exon gene localization from Leishmania (Viannia) panamensis and L. (Viannia) guyanensis. Different karyotypes were detected in human isolates circulating in endemic areas of Colombia. The presence of mini-exon gene sequences on chromosomes of different sizes, ranging from 370 to 800 kb in L. (V.) panamensis and from 500 to 800 kb in L. (V.) guyanensis, was observed and was neither strain nor species specific. In some cases, hybridization with 2 chromosomes in the same strain was observed. The variability of chromosomal localization of mini-exon gene sequences of these 2 species highlights the genetic variability of the Viannia subgenus and the potential utility of the mini-exon gene as a molecular epidemiologic marker. PMID- 11191901 TI - The symbiotic water mite Unionicola formosa (Acari: Unionicolidae) ingests mucus and tissue of its molluscan host. AB - Unionicola formosa is a symbiotic water mite that passes most of its life cycle in the mantle cavity of freshwater mussels. Although mites of this genus are often referred to as parasitic, little is known about their nutritional biology. A few species reportedly pierce the gill of a host mussel and ingest tissue or hemolymph. The present study was undertaken to identify possible sources of nutrition for U. formosa. To determine if mites ingested particulate matter in the mucous strand produced by a mussel during feeding, mussels with resident mites were exposed to a suspension of fluorescent microspheres. There was no evidence that U. formosa ingested the beads. Histochemical staining did, however, indicate a mucous material present in the midgut of the mites. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic assays revealed a high molecular weight component, consistent with a mucopolysaccharide, present both in the mussel gill and the mites. Results from western blots and an immunoaffinity binding assay with antibodies against mussel gill tissue and hemolymph also indicated that mites ingested host tissue. Whereas U. formosa probably does not ingest particulate material acquired by its host's suspension feeding, it is apparent that this mite utilizes host mucus, gill tissue, or hemolymph for at least part of its nutrition. PMID- 11191902 TI - Developmental and immunological aspects of Drosophila-parasitoid relationships. AB - The Drosophila-parasitic wasp (parasitoid) associations involve integrating adaptations of considerable complexity. This review focuses on some of the factors that influence these interactions including host immunity, nutrition and hormonal changes, and parasitoid virulence and mechanisms of immune suppression. PMID- 11191903 TI - Growth and emigration of third-stage larvae of Hysterothylacium aduncum (Nematoda: Anisakidae) in larval herring Clupea harengus. AB - The growth and emigration of Hystherothylacium aduncum in laboratory-reared herring larvae Clupea harengus was studied. Experimental infections of 36-day-old herring larvae resulted in 126 hosts infected with 306 H. aduncum larvae. Regression analyses showed a significant worm emigration from the rectum to the head of the fish, accompanied by an increase in worm body length. The emigration was independent of worm intensity, which suggests an ontogenetic process. Some worms departed from this pattern by moving posteriorly or by penetrating into the muscle, and in 5 cases, the larvae were observed to leave living fish. This individual variation has not been observed in previous studies and might be explained by host signals related to condition or development stage. Indirect evidence suggested parasite-induced mortality in the tanks due to the emigrations because only 4 of the 126 infected fish survived 8 days postinfection; the emigration of H. aduncum affected vital organs, such as the heart and brain, and the larvae penetrating or leaving the host's tissues can cause extensive damage to the delicate herring larvae. PMID- 11191904 TI - Completion of the life cycle of Sarcocystis neurona. AB - Sarcocystis neurona is the most important cause of a neurologic disease in horses, equine protozoal myeloencephalitis (EPM). The complete life cycle of S. neurona, including the description of sarcocysts and intermediate hosts, has not been completed until now. Opossums (Didelphis spp.) are definitive hosts, and horses and other mammals are aberrant hosts. In the present study, laboratory raised domestic cats (Felis domesticus) were fed sporocysts from the intestine of a naturally infected opossum (Didelphis virginiana). Microscopic sarcocysts, with a maximum size of 700 x 50 microm, developed in the muscles of the cats. The DNA of bradyzoites released from sarcocysts was confirmed as S. neurona. Laboratory raised opossums (D. virginiana) fed cat muscles containing the sarcocysts shed sporocysts in their feces. The sporocysts were approximately 10(-12) x 6.5-8.0 microm in size. Gamma interferon knockout mice fed sporocysts from experimentally infected opossums developed clinical sarcocystosis, and S. neurona was identified in their tissues using S. neurona-specific polyclonal rabbit serum. Two seronegative ponies fed sporocysts from an experimentally-infected opossum developed S. neurona-specific antibodies within 14 days. PMID- 11191905 TI - Simultaneous stable expression of neomycin phosphotransferase and green fluorescence protein genes in Trypanosoma cruzi. AB - The ribosomal RNA (rRNA) gene promoter was used to construct plasmid vectors that simultaneously express multiple exogenous genes in Trypanosoma cruzi. Vector pBSPANEO expresses neomycin phosphotransferase, and pPAGFPAN expresses both green fluorescent protein and neomycin phosphotransferase from a single promoter. Both vectors require the presence of the rRNA promoter for stable transfection; epimastigotes transfected with pPAGFPAN strongly fluoresced due to green fluorescent protein expression. Intact plasmids were rescued from the T. cruzi transfected population after >8 mo of culture, indicating stable replication of these vectors. Vectors were integrated into the rRNA locus by homologous recombination and into other loci, presumably by illegitimate recombination. Parasites bearing tandem concatamers of plasmids were also found among the transfectants. Transfectants expressing green fluorescent protein showed a bright green fluorescence distributed throughout the cell. Fluorescence was also detected in amastigotes after infection of mammalian cells with transfected parasites, indicating that the rRNA promoter can drive efficient expression of these reporter genes in multiple life-cycle stages of the parasite. Expression of the heterologous genes was detected after passage in mice or in the insect vector. These vectors will be useful for the genetic dissection of T. cruzi biology and pathogenesis. PMID- 11191906 TI - Molecular and morphological studies of Brazilian Trypanosoma evansi stocks: the total absence of kDNA in trypanosomes from both laboratory stocks and naturally infected domestic and wild mammals. AB - The kinetoplast DNA (kDNA) minicircle molecules of 14 Brazilian stocks of Trypanosoma evansi were studied by morphological approaches (Giemsa and 4'-6' diamidino-2-phenylindole staining and transmission electron microscopy) and molecular approaches (probing with an oligonucleotide complementary to the minicircle origin of replication and polymerase chain reaction amplification of a minicircle sequence). All methods indicated the absence of both a typical kinetoplast and kDNA minicircles, even in a very small number of parasites of a single stock or in small numbers of copies of molecules per cell. We did not detect any altered kDNA molecules. There were no kDNA molecules in either old or new stocks of T. evansi maintained by successive passages in mice. Similarly, no kDNA minicircles were detected in trypanosomes in blood smears from naturally infected domestic and wild animals. Thus, the total absence of kDNA in Brazilian stocks of T. evansi from both domestic and wild mammals is probably the natural state of Brazilian T. evansi. PMID- 11191907 TI - Clinical coccidiosis in raccoons (Procyon lotor). AB - Clinical coccidiosis was diagnosed in wild-caught and captive raccoons. Eimeria procyonis-like oocysts were seen in 15 of 15 captive raccoons. In 6 of 6 juvenile wild-caught raccoons examined at necropsy, endogenous coccidian stages were seen in the small intestine. Two types of schizonts (large and small) were identified. Large schizonts were up to 110 microm long, contained 10-microm-long merozoites, and were in crypt glandular epithelial cells. Smaller schizonts were 10 microm long, contained 5-microm-long merozoites, and were at the tips of the villi. Only a few gamonts and no oocysts were seen in sections. These stages were thought to be of E. procyonis. PMID- 11191908 TI - Redescription of Crepidostomum opeongoensis Caira, 1985 (Trematoda: Allocreadiidae) from fish hosts Hiodon alosoides and Hiodon tergisus (Osteichthyes: Hiodontidae). AB - Crepidostomum opeongoensis Caira, 1985 (Trematoda: Allocreadiidae) is redescribed from fish hosts Hiodon alosoides and Hiodon tergisus in southern Manitoba. The redescription adds details regarding the surface morphology and reproductive structures of the parasite not described previously. These include the characteristic tegumental papillae around the oral opening, paired papillae on the ventral and dorsal surfaces of the body, and tegumental bosses on the dorsal surface of the forebody. Crepidostomum opeongoensis co-occurred with its hypothesized sister species. Crepidostomum illinoiense, in all host individuals harboring the former, and both species are characteristic of hiodontids. The association of C. opeongoensis with hiodontids and the absence of hiodontids in Lake Opeongo where C. opeongoensis was originally reported indicate that the Algonquin Park region may have had hiodontids in the past and that the life cycle may be completed at present without the original fish host. PMID- 11191909 TI - Pterygodermatites (Mesopectines) senegalensis n. sp. (Nematoda, Rictulariidae), a parasite of Mastomys huberti (Rodentia, Muridae) in Senegal. AB - Pterygodermatites (Mesopectines) senegalensis n. sp. (Nematoda: Rictulariidae) is described from Mastomys huberti in Senegal. It differs from other species of the subgenus by the morphology of the head, which exhibits 4 simple cephalic papillae and a nearly axial buccal opening, the length of the spicules, the number of precloacal cuticular formations, and the absence of cephalic apophyses. PMID- 11191910 TI - Two new species of Litomosoides (Nematoda: Filarioidea) in Sigmodontines (Rodentia: Muridae) from Rio de La Plata marshland, Argentina. AB - Two new species of coelomic filarioid belonging to Litomosoides are described from sigmodontine murids from the Rio de La Plata marshland, Argentina. Litomosoides bonaerensis n. sp., a parasite of Oligoryzomys delticola, belongs to the carinii group and is close to L. silvai, which differs by the head and tail papillae, buccal capsule and cavity, area rugosa, and morphology of the microfilaria. Litomosoides oxymycteri n. sp., from Oxymycterus rufus, belongs to the sigmodontis group. Differential diagnosis is based on the morphology of the buccal capsule, the head and tail papillae, and microfilaria. The ectoparasitic gamasid Ornithonyssus bacoti, in which several Litomosoides species develop, has been recovered from sigmodontines trapped in the study. PMID- 11191911 TI - Phylogenetic relationships among species of Stilestrongylus Freitas, Lent and Almeida, 1937 (Trichostrongyloidea: Heligmonellidae: Nippostrongylinae), parasites of myomorph rodents (Rodentia: Muridae) in the Neotropics. AB - The phylogenetic relationships of 14 species of Stilestrongylus were analyzed using the comparative morphology of 21 characters. We obtained 2 shortest trees of 50 steps, with a consistency index of 0.540 and 25 apomorphic character states. Ingroup monophyly was supported on these trees by 2 and 3 synapomorphies, respectively, and the ingroup was defined by the following characters: greater number of ventral ridges relative to the number of ridges dorsally, asymmetric bursa, and externodorsal rays differing in size. Sister-group relationships among Stilestrongylus and the other genera designated as outgroups are relatively consistent with those postulated by Durette-Desset's in a classification of the Nippostrongylinae. The ancestor of the species groups comprising Hassalstrongylus, Guerrerostrongylus, and Stilestrongylus originated and diversified in murids in the Neotropical region. Species of Hassalstrongylus occur in rodents between southeastern North America and the eastern part of South America (Brazil and Argentina), whereas species of Guerrerostrongylus and Stilestrongylus diversified exclusively in rodents in the Neotropics. PMID- 11191912 TI - Purification of first-stage larvae of Elaphostrongylus cervi (Nematoda: Protostrongylidae) from feces. AB - Parasites are often found in a milieu that requires extensive preparation and labor-intensive cleaning before they are suitable for use in analytical procedures. Application of modern techniques in immunology and molecular biology demands pure yields of parasites. To purify first-stage (L1) larvae of Elaphostrongylus cervi, fecal suspensions from an infected red deer were processed by the Baermann method and embedded in a gel matrix with the objective of selectively trapping fecal debris. About half the number (50.9%) of embedded larvae migrated out of the gel within a 24-hr period and were collected as clean parasite suspensions, virtually free from fecal debris. The numbers of L1 emigrating from gels were inversely proportional to the fecal debris content and the thickness of the gel. Removal of fecal debris from Baermann fluid by sieving prior to gel embedment enhanced the yield of pure L1. PMID- 11191913 TI - Infection by Paragonimus miyazakii cercariae of their crab hosts, Geothelphusa dehaani, by percutaneous penetration. AB - Identification of the transmission routes of the trematode parasite Paragonimus miyazakii into different intermediate hosts would help to explain the natural distribution of the parasite. The behavior of P. miyazakii cercariae released from snails into water and in the presence of a living host or a whole crab leg was observed by stereoscopic or light microscopy at various times after exposure started. On encountering a crab leg or cheliped, the cercariae became entangled with the host via mucoid strands arising from the cercariae. Within 3 hr, most cercariae were attached to the host; cuticular penetration took between 5 and 6 hr, after which cercariae were found in the cavity of the leg. Crabs examined 102 149 days after exposure to the cercariae contained fully developed metacercariae. The metacercariae were fed to 2 rats, and the rats were killed 83 or 111 days later. Some of the metacercariae had reached maturity in the rats. That the cercariae were not ingested by the crabs but penetrated the crabs percutaneously (through hard as well as soft tissue) means that transmission can occur even in areas in which crabs and the host snails do not coexist, as they would if the usual route were oral (when the crabs ate infected snails). PMID- 11191914 TI - Susceptibility of species A, B, and C of Anopheles culicifacies complex to Plasmodium yoelii yoelii and Plasmodium vinckei petteri infections. AB - The comparative susceptibilities of colonized species A, B, and C of Anopheles culicifacies complex and Anopheles stephensi were determined for 2 rodent malaria parasites Plasmodium vinckei petteri and Plasmodium yoelii yoelii. All the 3 members of the complex were found to support complete sporogony with varying success. Controls, A. stephensi, become readily infected, with >70% developing oocysts. Of the test groups, species A had the highest percentage of mosquitoes with oocysts (>25%) and sporozoites (>15%). Anopheles culicifacies species B were least susceptible; less than 10% had oocysts and sporozoites in the salivary glands. The results demonstrate that A. culicifacies species A is most susceptible and species B is least susceptible to infections with both the parasites. PMID- 11191915 TI - Comparative biology of Uncinaria spp. in the California sea lion (Zalophus californianus) and the northern fur seal (Callorhinus ursinus) in California. AB - Studies on several aspects of the life cycle of hookworms (Uncinaria spp.) in the California sea lion (Zalophus californianus) and northern fur seal (Callorhinus ursinus) were conducted on material collected on San Miguel Island (SMI), California and at The Marine Mammal Center, Sausalito, California in 1997, 1998, and 1999. Examination of Z. californianus intestines for adult hookworms and feces for eggs revealed that longevity of these parasites in pups is about 6-8 mo, and infections are probably not present in older sea lions. Parasitic third stage larvae (L3) were recovered from the ventral abdominal tissue of Z. californianus, suggesting transmammary transmission. Callorhinus ursinus pups had no hookworm eggs in their feces or adult worms (except for 1 probable contaminant) in their intestines in the fall and early winter, revealing that adult Uncinaria spp. are spontaneously lost at <3 mo of age of the pups. Sand samples from rookeries, used by both Z. californianus and C. ursinus, on SMI were negative for free-living, L3 in summer months but positive in fall and winter months, indicating seasonality occurred. PMID- 11191917 TI - Effect of the antimicrobial peptide, D-hecate, on trichomonads. AB - Tritrichomonas foetus and Trichomonas vaginalis are protozoan parasites that cause sexually transmitted diseases in cattle and humans, respectively. There is a need for new antimicrobial agents to treat or prevent trichomoniasis because there are currently no approved chemotherapeutic agents against T. foetus and resistance of T. vaginalis to metronidazole does occur. Therefore, we evaluated the effect of a novel antimicrobial peptide, D-hecate, on the viability of 6 isolates of T. foetus and T. vaginalis in vitro. Tritrichomonas foetus and T. vaginalis were grown to mid log phase (24 hr) or late log/stationary phase (48 hr). Parasites at 10(6)/ml were mixed with equal volumes of D-hecate to final concentrations of 10 microM, 20 microM. and 40 microM of D-hecate. Controls had minimal essential medium (MEM) alone. The numbers of viable parasites were determined microscopically after 10, 20, and 30 min of incubation at 37 C with D hecate or MEM. Our results show that D-hecate killed all 6 isolates of T. foetus and T. vaginalis evaluated. The killing effect was dependent on the concentration of the peptide, incubation time, and phase of growth of the parasites. Ultrastructural studies of parasites treated with 10 microM of D-hecate revealed extensive damage to the plasma membrane of most T. foetus and T. vaginalis cells, while a few cells were distorted but remained intact. D-Hecate may be a useful chemotherapeutic agent for the treatment of trichomoniasis. PMID- 11191916 TI - Detection of the Cryptosporidium parvum "human" genotype in a dugong (Dugong dugon). AB - The Cryptosporidium "human" genotype was identified in a paraffin-embedded tissue section from a dugong (Dugong dugon) by 2 independent laboratories. DNA sequencing and polymerase chain reaction/restriction fragment length polymorphism analysis of the 18S ribosomal RNA gene and the acetyl CoA synthethase gene clearly identified the genotype as that of the Cryptosporidium variant that infects humans. This is the first report of the human Cryptosporidium genotype in a nonprimate host. PMID- 11191918 TI - Occurrence of Sanguinicola occidentalis Van Cleave and Mueller, 1932 in Perca flavescens and Campeloma decisum from a Michigan creek. AB - Sanguinicola occidentalis (Trematoda: Sanguinicolidae) infected 58 (48%) of 120 yellow perch collected in 1997 and 40 (50%) of 80 yellow perch collected in 1998 from Silver Creek in lower Michigan. The mean intensity and mean abundance of this blood fluke were higher in 1998 than in 1997. The fluke was found in the bulbous arteriosus of the perch heart, free in the petri dishes when the gill filaments were teased apart, and in the body cavity washings, and 1 individual was associated with an eye. Of the 269 S. occidentalis examined from perch, none had eggs. Most perch examined and infected were only 1+ yr in age. Spearman's correlation coefficients between S. occidentalis intensity and host length in 1997 and 1998 were not significant. An additional 25 yellow perch (0+ yr in age) collected in 1998 were not infected. Thirty-seven (33%) of 113 snails (Campeloma decisum) examined in July and August 1999 from Silver Creek were infected with S. occidentalis. PMID- 11191919 TI - Monoclonal antibodies to Hammondia hammondi allowing immunological differentiation from Toxoplasma gondii. AB - Five murine monoclonal antibodies (MAbs) were developed against purified sporozoites of Hammondia hammondi. Despite a large antigenic similarity between the 2 closely related coccidia, H. hammondi and Toxoplasma gondii, these MAbs only reacted with H. hammondi. Three MAbs, ID3, 3F2, and 4C9-7, recognized antigens of 38 kDa localized in rhoptries (1D3), in rhoptries and in oocyst and cyst walls (3F2), and in rhoptries and the apical region (4C9-7). Another MAb, 4C9-10, reacted with a 27-kDa antigen in dense granules of sporozoites and tachyzoites, and MAB 11B3 labeled an antigen of >94 kDa located in the pellicular membrane of the 3 stages of the parasite. These MAbs could be used for a rapid discrimination of the 2 coccidia in epidemiological studies or for diagnostic purposes in tissues. PMID- 11191920 TI - A random amplified polymorphic DNA polymerase chain reaction technique that differentiates between Neospora species. AB - Neospora caninum is a recently described coccidial parasite that was first isolated from a dog in 1988 and has subsequently been shown to infect a wide range of mammals. Neospora hughesi, a new species of this genus, has recently been isolated from the spinal cord of horses showing clinical signs of equine protozoal myeloencephalitis. The random amplified polymorphic DNA polymerase chain reaction technique is capable of differentiating between N. caninum and N. hughesi. PMID- 11191921 TI - The nuclear rDNA region of Gyrodactylus arcuatus and G. branchicus (Monogenea: Gyrodactylidae). AB - The primary structure of the ribosomal DNA internal transcribed spacers (ITS-1 and ITS-2) and 5.8S rRNA gene were used to characterize and identify 2 monogenean species of Gyrodacrylus living externally on the threespine stickleback (Gasterosteus aculeatus). The ITS region was amplified by PCR from freshwater, brackish, and marine isolates of Gyrodactylus arcuatus and G. branchicus, and the ends of the coding regions were identified by comparative alignment. No intraspecific and very low interspecific variation were observed in the 5.8S rRNA gene; high inter- and low intraspecific variation were revealed in the ITS-1 and ITS-2 regions. The morphological species identification was in all cases confirmed by the molecular identification. Intraspecifically, samples from 2 locations in the North Sea could be differentiated, but the Baltic sample resembled North Sea genotypes. Our approach offers perspectives for a multimetric genetical, morphometrical, and ecological taxonomy of the genus Gyrodactylus. PMID- 11191922 TI - [Development of child guidance clinics in Germany--an overview]. AB - The development of child guidance centres began before 1910 with single institutions characterized by various subject areas (medicine, pedagogy, psychology) as well as by the connection of counselling and therapeutic treatments. Since about 1920 it has become customary to call such institutions child guidance centres. A consistent development lead to the fact that in the Child and Adolescent Aid Law of 1990 child guidance centres are called institutions which are capable of handling different problems with a multi professional staff and various methods, and offering counselling and treatments as required. People seeking advice shall be able to contact child guidance centres directly of their own free will. PMID- 11191923 TI - [Process of institutional child guidance counseling reflected by the Central Continuing Education of the Federal Conference for Child Guidance Counseling]. AB - The Bundeskonferenz fur Erziehungsberatung (bke) is the federation for child guidance and family-counseling in Germany. Members are the working groups for child guidance and family-counseling of the Lander, where the employees of the child guidance are organized. The federation was founded in 1962. It is sponsored by the Federal Ministry for Family, Seniors, Women and Youth. Further education for professional youth workers is central mission of bke. The constitution of the federation lais down these contents. Every autumn the bke publishes the program for further education for the following year in a brochure called Zentrale Weiterbildung--the program for child guidance, family counseling and youth counseling. A special Kommission Zentrale Weiterbildung acquires the contents of the program for further education und selects the referents. Since 1968 the Zentrale Weiterbildung of Bundeskonferenz fur Erziehungsberatung offers events for professional youth workers in child guidance, family counseling. The program for further education contributes the quality of the institution of child guidance. After a time with above average use of the program for further education with therapeutical focal point, the orientation of the program changes to child and youth services. A constant number of counselors use the program. Beside the change of contents there was a change to effectiveness of contents and a reduction of participants. PMID- 11191924 TI - [Quality of child guidance counseling--current developments at the beginning of the 21st century]. AB - Development of quality is not a new discussion in child guidance. There has been a long tradition about this theme. The continuously changing conditions of society and law demands child guidance on the other hand to changing reactions also. In modern child guidance we can find them in changed concepts and methods. So quality will be developed. The complete analysis shows us also, were new discussions are necessary. PMID- 11191925 TI - [Where are the children in family counseling? Results of an explorative study]. AB - Since the late seventies the family setting has become a normal model in counseling, not least because of the systemic change in psychotherapy. The lack of methodologically well-founded considerations on how to involve the children in the family talk is therefore even more surprising. In the present study 40 counselors were interviewed how they propose to fill the special gap in their practical work, what strategies they have developed to involve children and how important for them children are in the family talk. The result was that the majority of the counselors are adult oriented in their activities and rarely include the children actively in the interactive proceedings. Nevertheless all those interviewed regarded their presence as necessary because they provide helpful diagnostic assistance in uncovering and recognizing parental problems and relational conflicts. PMID- 11191926 TI - [Adventure conflict--early prevention of violence in child day care centers and primary schools]. AB - The primary target group of the program are children aged 3 to 10 years attending child day care centres and primary schools. The intermediate target groups are teachers and parents. The objectives for the primary target group are to promote good social behavior, to develop constructive solutions to conflict and to set out rules and limits for children. The objectives for the intermediate target groups are to learn constructive ways of handling conflicts in each team, to improve cooperation in the teams and between teachers and parents and to raise awareness among parents. The work is done on three levels: children, teachers and parents. It provides training, group work, work with creative media, relaxation and movement exercises, theory, role play and advice on organization. PMID- 11191927 TI - Electrodiagnosis of polyneuropathy. AB - Electrodiagnostic studies comprising electromyography (EMG) and nerve conduction studies (NCS) are well-established objective methods for the diagnosis, quantification and classification of polyneuropathies (PNP). This paper reviews examination techniques, their pathophysiological interpretation, examination strategies and diagnostic criteria for the diagnosis and classification of a PNP. The routine electrodiagnostic evaluation includes sensory NCSs performed with surface or needle electrodes, motor NCSs, F-wave studies and EMG by qualitative or quantitative techniques. Sensory NCSs and F-wave studies have a high sensitivity in PNPs and the different techniques complement each other. The distinction between a PNP with predominantly axonal loss and a PNP with predominantly demyelination is one of the major aims of the electrophysiological examination. There are, however, large variation in suggested criteria for predominantly demyelination. The degree of slowing in conduction taken to indicate demyelination varies between a decrease of 50 to 30% from mean of controls, distal latency prolongation criteria vary from 35% to 70% of mean of controls, F-wave latency prolongation criteria vary from 120% to 150% of upper limit of controls, and criteria for partial motor conduction block vary from 11 to 50% reduction of CMAP amplitude and/or area between proximal and distal stimulation. Needle EMG studies may be valuable in order to detect and quantify denervation activity, to assess chronicity by an evaluation of the extent of reinnervation, and to evaluate the topographical distribution of changes. It is concluded that electrodiagnostic studies are valuable in patients with suspected PNP and the results may have consequences for prognosis and therapy of individual patients. Large variation in examination techniques, strategies, interpretations and diagnostic criteria have been found among electromyographers and it is suggested that the value of electrodiagnostic studies may be further improved by international standardisation. PMID- 11191928 TI - Neurophysiological characterization of parkinsonian syndromes. AB - Electrophysiological examination can provide relevant information on functional abnormalities in patients with parkinsonism. The combined use of various electrodiagnostic techniques can contribute to the diagnosis of the illness, to its correct classification and differentiation from other diseases with a clinically similar presentation, and in particular the identification of the pathophysiological processes underlying some of the signs and symptoms characterizing the movement disorder. Tests which are useful in the differential diagnosis of various parkinsonian syndromes can now be performed in most electrodiagnostic laboratories. This article reviews some of the most relevant observations provided by neurophysiological studies on patients with parkinsonism, with a special focus on those that could be of more value in neurological clinical practice through their contribution to the characterization of the disease or to the recognition of underlying pathophysiological processes. PMID- 11191929 TI - Abnormality of N30 somatosensory evoked potentials in Parkinson's disease: a multidisciplinary approach. AB - PURPOSE OF THE STUDY: Assess the N30 component of median nerve somatosensory evoked potentials (SEPs) in patients with Parkinson's disease (PD) and correlate its parameters with the severity of the disease, general cognitive ability and regional cerebral blood flow (rCBF). PATIENTS AND METHODS: Twenty-three non demented, non-depressed PD patients (at stage II and III of the disease) and 23 age- and education-matched normal controls were enrolled in the study. SEPs were elicited by median nerve stimulation. PD patients' cognitive ability was assessed by means of: 1) Raven's Colored Progressive Matrices (RCPM); 2) the Test of Non Verbal Intelligence (TONI-2); and 3) the Wisconsin Card Sorting Test (WCST). The patients' rCBF was evaluated by HMPAO SPECT. RESULTS: There was no difference between SEP N30 latency in PD patients and controls (P > 0.05). The P20-N30 peak to-peak amplitude was lower in PD patients bilaterally (P < 0.05), and the amplitude of N30-P40 was lower on the right side only (P < 0.05). A significant increase in the amplitude ratio P14-N20/P20-N30 was observed in PD patients (P < 0.05). The correlation of these findings with the clinical parameters of the disease, and notably motor signs, was not significant. Of the three neuropsychological tests only the RCPM showed a positive relation to right P20 N30 amplitude. Regression analysis between SEP parameters and rCBF showed a correlation of N30 amplitude with blood flow in parietal cortical areas, but not in frontal regions. PMID- 11191930 TI - No, some types of nonconvulsive status epilepticus cause little permanent neurologic sequelae (or: "the cure may be worse than the disease"). AB - Nonconvulsive status epilepticus (NCSE) is characterized by a cognitive or behavioral change which lasts for at least 30 minutes, with EEG evidence of seizures. Although there is little argument that generalized nonconvulsive status epilepticus (GNSE) does not cause lasting deficits, there is still debate regarding the morbidity of complex partial status epilepticus (CPSE). Because the EEG is used for diagnosis, a strong argument can be made that NCSE is significantly under-recognized and diagnosed. Furthermore, since the documented cases of permanent neurologic sequelae are few, the potential permanent morbidity from CPSE may be significantly exaggerated. The literature indicates that comatose patients have a poor prognosis largely as a result of comorbid conditions and coma, whereas lightly obtunded or slightly confused patients with NCSE have little or no sequelae. Patients with NCSE may suffer (hypotension and respiratory suppression) from iatrogenic 'aggressive' treatment with intravenous anti-epileptic drugs (IV-AEDs), and the findings in the literature indicate that subjects treated with benzodiazepines may have a worse prognosis. The clinician must balance the potential but rare neurologic morbidity associated with NCSE against the not infrequent morbidity caused by IV-AEDs. Better stratification of the level of consciousness and comorbid conditions is needed when evaluating outcomes so as to clearly distinguish among the deficits due to: comorbid conditions; the effects of treatment and the effects of status epilepticus (SE) proper. PMID- 11191931 TI - Severe but reversible encephalopathy associated with cefepime. AB - In this study, a report has been made of 19 cases of severe encephalopathy in patients with renal impairment who were treated during the last three years for various infections with cefepime, a new parenteral cephalosporin antibiotic. All patients (aged 57 to 91 years) presented a prolonged confusional state associated with diffuse rhythmic non-reactive triphasic sharp waves on the EEG. All the electroclinical symptomatology disappeared within 24-48 hours after discontinuation of drug administration. A clear relation was found between encephalopathy and cefepime intake. These observations underline the fact that the cefepime dosage should be reduced in renally impaired patients. PMID- 11191932 TI - Surgery for atrial fibrillation--use of a sledgehammer to crack a nut? PMID- 11191933 TI - Appropriateness of percutaneous transluminal coronary angioplasty in stable and unstable angina pectoris. A review. PMID- 11191934 TI - Myocardial ischaemia and neuroendocrine stress: metabolic consequences and possibilities. PMID- 11191935 TI - Arterial revascularization: evidence or presumption? PMID- 11191936 TI - Hypothesis: the recent decline in coronary heart disease mortality--mainly a shift from fatal to non-fatal events? AB - OBJECTIVES: A marked, sequential decline in coronary heart disease (CHD) mortality is established, but not its causes. Does it reflect modern treatment effects or a spinoff of primary prevention? The aim of this study was to explore this issue using a prospective cohort follow-up design. DESIGN: In 1972-1975 and 1980-1982 Cohorts 1 (n = 613) and 2 (n = 667) of identical age (males, mean 56 years) were examined, and thereafter followed closely for 14 years. CHD risk- and treatment patterns, incidence of non-fatal myocardial infarctions (MIs) and total , cardiovascular and CHD mortality rates were studied. RESULTS: CHD risk factors were more favourable, medical treatment more aggressive and 14-years CHD mortality, as expected, lower in Cohort 2 (7.7%/4.8%, p = 0.032). However, hospital- and prospective ECG data revealed opposite trends in non-fatal cohort CHD incidence, and aggregated numbers of CHD deaths and non-fatal MI cases were 16.7%/16.0% in Cohort 1/2 (p = 0.90). CONCLUSIONS: A marked, sequential reduction in CHD mortality was followed by a reciprocal increase in non-fatal MIs. This phenomenon may prevail in low CHD-endemic areas, and may call for altered primary preventive measures for reduction in total CHD incidence. PMID- 11191937 TI - Amlodipine versus slow release metoprolol in the treatment of stable exertional angina pectoris (AMSA). AB - OBJECTIVES: To compare the effects of amlodipine and slow release metoprolol on subjective symptoms and signs of ischaemia during bicycle ergometric exercise tests in patients with stable angina pectoris. DESIGN: A randomized double-blind comparison of the two drugs in patients with documented coronary disease required to have at least three attacks of angina per week and to perform a symptom limited exercise test with significant signs of ischaemia in the ECG. RESULTS: Out of 127 patients, 117 completed the study. Both amlodipine and metoprolol significantly increased total exercise time, total workload, time to onset of angina and time to 1 mm ST-depression with no significant differences between the drugs. Amlodipine was significantly more efficient than metoprolol in reducing ST depression at maximum workload. Diary data revealed no differences in patients' self-rating of drug effects. CONCLUSIONS: Judged by suppression of subjective symptoms and performance on exercise tolerance tests amlodipine represents a useful alternative to metoprolol as monotherapy in stable angina pectoris. PMID- 11191938 TI - The Maze operation for treatment of atrial fibrillation. Early clinical experience in a Scandinavian institution. AB - The Maze operation is a potentially curative surgical option in patients with disabling atrial fibrillation (AF) refractory to conventional treatment. The aim of this study was to evaluate the initial 4-year Maze experience in our institution. The study included 26 patients (19 males, mean age 55 years) who had undergone the Maze (III) operation between 1994 and 1998. Nine patients had surgery for concomitant heart disease. Follow-up was 3-55 (median 18) months. No deaths or neurological complications occurred; 22 patients are at present in regular sinus-, or junctional rhythm, 2 patients have permanent atrial pacing for symptomatic sinus node dysfunction, and 2 patients have had persistent AF, post surgery. Sinus node dysfunctions were detected in five patients, though not requiring pacemakers. Out of the total 26 patients, 23 are free of anti arrhythmic drugs. Echocardiographic signs of left atrial contraction were recorded in 50% of the patients. The Maze operation offers a safe alternative to conventional therapy, with attractive results justifying expansion in the use of this treatment for AF. PMID- 11191939 TI - Protective effect of unstable angina in coronary artery bypass surgery. AB - OBJECTIVE: To test the hypothesis that recent ischaemic episodes in unstable cases have a protective effect on coronary artery bypass graft (CABG) patients. MATERIALS AND METHODS: Twenty unstable patients with ischaemic episodes within 3 days before operation were compared with 20 stable patients. Haemodynamic data were monitored up to the first postoperative day. Biochemical markers were measured up to the second postoperative day. RESULTS: The cardiac index decreased at 1 and 6 h after declamping in the stable group (89% and 97% of baseline) but increased in unstable patients (104% and 122%, p =0.038 and 0.036, respectively). The depression in the right ventricular stroke work index was significantly attenuated in the unstable group (58%, 67% and 83% in stable and 90%, 97% and 117% in unstable patients, p = 0.027, 0.010 and 0.049 at 1 and 6 h after declamping and 1st POD). The release of cardiac troponin I (CTnI) and CK-MB was significantly lower in the unstable group at 6 h after declamping (5.6 +/- 2.9 and 19.0 +/- 6.3 microg/l in unstable vs 17.4 +/- 9.6 and 25.8 +/- 12.3 microg/l in stable patients, p = 0.000 and 0.039, respectively). CONCLUSION: Recent unstable angina before CABG might act as an ischaemic preconditioning stimulus and could improve haemodynamic function and cellular viability. Delayed preconditioning most likely causes this protective effect. PMID- 11191940 TI - Evaluation of left ventricular function in coronary bypass surgery. AB - OBJECTIVES: To evaluate non-invasive indexes measuring systolic and diastolic ventricular function. Eleven coronary artery bypass grafting (CABG) patients were investigated in order to assess the ability of preoperative ejection fraction (EF) and end diastolic pressure (EDP) to predict left ventricular function determined non-invasively at surgery. DESIGN: End-systolic elastance (Ees) was assessed perioperatively using transoesophageal echocardiographic area estimation and arterial pressure monitoring during preload variations (caval balloon). Diastolic function was evaluated using three different echo/Doppler indexes. RESULTS: EF correlated positively to Ees (r = 0.69, p = 0.03). No correlations were found between EDP and the perioperative diastolic indexes. Ees fell from pre bypass to post-bypass (from 9.0 +/- 2.7 to 4.7 +/- 1.7 mmHg/cm2, mean +/- SD, p < 0.001), but no alterations in diastolic parameters occurred. CONCLUSIONS: A positive correlation was found between preoperative EF and Ees at surgery. The semi-invasive Ees detected a systolic "stunning" after cardiopulmonary bypass and is promising as a surveillance tool for left ventricular perioperative function and treatment. No correlations between preoperative EDP and non-invasive diastolic indexes were found, and assessment of perioperative diastolic function needs further refinement. PMID- 11191941 TI - Microdialysis of blood from the cardiac venous outflow: a technique for monitoring myocardial ischemia. AB - OBJECTIVE: To evaluate the possibility of using microdialysis of blood from the great cardiac vein for detecting myocardial ischemia. DESIGN: Microdialysis catheters were placed in the great cardiac vein and the left atrium of pigs for analysis of lactate, glycerol, pyruvate and glucose. Blood samples were drawn for measurement of aspartate aminotransferase, alanine aminotransferase, lactic dehydrogenase and myoglobin with the objective of verifying myocardial damage. Ischemia was induced for 3 h. RESULTS: Fifteen minutes after induction of ischemia a significant elevation of lactate to 917 +/- 223%; p < 0.001 in the great cardiac vein could be registered. No significant changes in lactate levels were detected in the left atrium. Changes in glycerol and pyruvate showed similar patterns, with an increase to 722 +/- 297%; p < 0.001 and to 281 +/- 56%; p < 0.05, respectively. The outflow of aspartate aminotransferase and myoglobine in the great cardiac vein increased significantly. CONCLUSION: Early detection of metabolic substances is possible through the assessment of metabolic substances using microdialysis in the great cardiac vein. PMID- 11191942 TI - Primary reconstruction of interrupted aortic arch--surgical management and results. AB - Type B interrupted aortic arch associated with other extracardiac and intracardiac congenital lesions is a lethal defect. Surgical management with a one- or two-stage approach is complex, difficult and associated with high morbidity and mortality. Between January 1996 and December 1999, 5 consecutive patients with type B interrupted aortic arch were operated on. The group included 3 girls and 2 boys weighing from 2.4 kg to 3.5 kg (mean 2.84 kg) and aged from 4 to 35 days (mean 15 days). All patients underwent a primary reconstruction of the aortic arch and one-stage repair of the associated heart defects. Two patients developed symptoms of mild aortic arch narrowing 7-12 months postoperatively. Balloon angioplasty of the obstructed site was successfully carried out in one of the patients. In the second child, angioplasty was not successful and surgery was used. All the patients survived and are being followed-up. This experience supports a strategy of primary one-stage repair of IAA type B, including direct anastomosis for aortic arch reconstruction, and all associated heart anomalies in the neonatal period. PMID- 11191943 TI - Short-term results after aortic valve replacement with stentless xenografts in elderly patients. AB - OBJECTIVE: Our aim was to chart the short-term results of the first 75 of our patients who had undergone first-time aortic valve replacement (AVR) with stentless xenografts. DESIGN: Our study included a complete follow-up (mean/max. 1.5/3.7 years) of the first 75 patients (42 males, 33 females; mean age 74, range 61-84 years) who underwent a first AVR with stentless xenografts. RESULTS: Forty three percent of patients were in functional class II and 57% in classes III-IV preoperatively. Coronary artery bypass grafting (CABG) was performed in 33 patients. Early mortality (< or = 30 days) was 6.7%, with no significant relation to CABG or age. Crude survival was 81% (95% confidence interval, CI: 71-91 %) at 3 years. Using a multivariate analysis, we identified a low left ventricular ejection fraction as a predictor of early and late mortality. Late survival (early mortality excluded) was comparable with the survival of a matched Danish background population. There were six embolic events (all cerebral: 3 minor, 1 major, 2 fatal), while two patients underwent redo-AVR because of either endocarditis (fatal) or aortic regurgitation caused by malaligned commissures. There were no other valve-related complications. Cumulative freedom was 89% (95% CI: 79-99%) for embolism and 86% (95% CI: 76-96 %) for all complications at 3 years. At the end of the study, 64% of the survivors were in functional class I, 34% were in class II and 2% in class III. CONCLUSIONS: Considering the age composition of our patients, and compared with international results, our early mortality rates were acceptable. The absence of late excess mortality compared with the background population and the functional status at end-of-study may indicate the potential haemodynamic advantages of stentless aortic valves, at least in the short term. PMID- 11191944 TI - Predictors of atrial fibrillation in patients undergoing surgery for ischemic heart disease. AB - OBJECTIVES: Atrial fibrillation (AF) remains a common problem after cardiac surgery. AF increases the risk for stroke and is associated with increased length of hospitalization. The aim of this study was to analyze risk factors for postoperative AF in a uniformly managed cohort of patients. DESIGN: The records of 775 consecutive patients undergoing coronary artery bypass grafting (CABG) or CABG + valve procedures were examined. Forward stepwise multiple logistic regression analysis was used for statistical evaluation. RESULTS: Mean age was 64.6 +/- 8.7 years. The incidence of AF was 29.1% in patients undergoing isolated CABG and 48.6% after CABG + valve procedures. Multivariate analysis identified advanced age (p = 0.000003), low postoperative mixed venous oxygen saturation (p = 0.0018), hypertension (p = 0.0059), preoperative history of AF (p = 0.023) and the need for mechanical circulatory support (p = 0.030) as predictors for postoperative AF. CONCLUSIONS: In agreement with previous studies, advanced age was the most important predictor of AF. Hypertension, history of AF and signs of circulatory failure were also predictive of AF. Preventive measures against AF should preferably be tested in high-risk populations, such as elderly patients. PMID- 11191945 TI - Perioperative myocardial infarction in cardiac surgery--risk factors and consequences. A case control study. AB - OBJECTIVE: The aim of the study was to analyze risk factors and clinical outcome in patients sustaining perioperative myocardial infarction (PMI) after cardiac surgery. DESIGN: A retrospective, case control study was conducted, in which 42 patients fulfilling both Q-wave criteria and enzyme criteria for PMI, or autopsy diagnosis, from a cohort of 1147 operated on during the same time period were compared with matched controls. A follow-up by telephone interview was conducted, on average 24 months after the operation. RESULTS: Unstable angina, peripheral vascular disease, short stature and low body weight were more prevalent in the PMI group. Intraoperative remarks of poor quality coronary vessels and incomplete revascularization were more frequent in the PMI group; 30-day mortality was 24% in the PMI group vs 0% in the control group (p < 0.01). The postoperative course was more complicated and protracted in the PMI group. At follow-up, the control group managed significantly better with regard to freedom from angina and the need for nitroglycerine. However, 24 of the 30 survivors in the PMI group reported an improved quality of life after surgery. CONCLUSIONS: We found that PMI was mainly associated with coronary surgery and that unstable angina was the most important preoperative risk factor for PMI. Poorer conditions for revascularization may explain some of the infarcts and could also contribute to the impaired long-term outcome in the PMI group. PMID- 11191946 TI - Five-year experience with a suture annuloplasty for mitral valve repair. AB - We present five years' experience with mitral plication annuloplasty, performed with a semicircular buttressed suture around the posterior leaflet in 130 patients (mean age 58 +/- 11 years) with primary mitral valve disease (n = 71) or functional mitral regurgitation (n = 59). In 65 cases the mitral valve itself was also repaired. Concomitant myocardial revascularization was performed in 40 cases and aortic valve replacement in 43. All but three patients were followed up (97.6%). Postoperative echocardiography showed acceptable mitral area (2.28 +/- 0.39 cm2) and good valve competence in all cases. Inhospital mortality was 3% and late mortality 4.8%. During the follow-up period (22.8 +/- 10.9 months) 8 patients (6.6%) required mitral valve replacement because of progression of native valve disease (n = 4), technical failure (2) or expansion of the annuloplasty suture (2). Mitral annuloplasty thus can be performed simply and with good results, using a strong, non-stretchable buttressed suture. This procedure can be an inexpensive alternative to ring implantation. PMID- 11191947 TI - Closed mitral commissurotomy in Archangel, Northern Russia, 1965-1993. Operative assessment of 367 patients operated on for rheumatic mitral stenosis. AB - OBJECTIVE: Preoperative and operative assessment of the 367 patients operated on for rheumatic mitral stenosis with closed mitral commissurotomy (CMC) at the regional hospital in Archangel, northwest Russia, between 1965 and 1993. DESIGN: Retrospective survey. RESULTS: Mean age at first attack of rheumatic fever was 15 years +/- 1.09 years. Mean age at time of surgery was 33.4 years +/- 0.92. Preoperatively, most patients (67%, n = 245) were in New York Heart Association stage III; 29% (n = 107) in stage IV. Digital commissurotomy alone was performed in 16% (n = 57) and a transventricular dilator was used in 84% (n = 310). Operative blood loss was average (384.4 ml +/- 34 ml); 20% (n = 73) developed wound infection, 21% (n = 77) pericarditis. In-hospital stay was above 50 days for both sexes. In-hospital mortality was 1.6% (n = 6). CONCLUSION: Rheumatic heart disease developed rapidly in these patients. CMC has a place as a low cost treatment of mitral stenosis when a heart lung machine is not available. PMID- 11191948 TI - Immunostaining for detecting lymph node metastases in non-small cell lung cancer. AB - OBJECTIVE: To detect lymph node metastases by immunohistochemistry, where previously undetected by routine histopathology. DESIGN: Immunostaining was carried out for high- and low molecular weight cytokeratins, and Ber-EP4 in 19 consecutive lung cancer patients who had undergone systematic mediastinal lymph node dissection. RESULTS: Eleven (58%) epidermoid carcinomas, 6 (32%) adenocarcinomas, and 2 (10%) bronchiolo-alveolar carcinomas were detected. These included 4 (21%) stage IA carcinomas, 6 (32%) stage IB, 6 (32%) stage IIB, 1 (5%) stage IIIB and 2 (10%) stage IV. Immunostaining did not reveal any undetected metastases. Two patients (squamous cell carcinoma T1N0; adenocarcinoma T1N0) had metastases (skeletal; ipsilateral lung) at time of surgery, and one patient (squamous cell carcinoma T2N0) had a regional and systemic relapse 10 months later. Serial sectioning with immunostaining of the lymph nodes from these three patients was also negative. CONCLUSION: We conclude that, even with the use of immunostaining, negative lymph nodes will not assure a good prognosis, and different determinants probably exist for lymphatic and hematogenic metastases in non-small cell lung cancer. PMID- 11191949 TI - Coronary artery bypass surgery after previous pneumonectomy-two case reports. AB - Coronary artery surgery after previous pneumonectomy should be considered a high risk procedure. We describe two cases with associated morbidity and mortality. Pathogenetic mechanisms are discussed. PMID- 11191950 TI - Teratoma presenting as a cystic lesion on the chest wall. AB - A 28-year-old woman presented with a rare case of chest-wall teratoma. Computed tomography of a cystic lesion located in the anterior chest wall revealed a hyperdense object with the appearance of a tooth. The cystic mass was totally excised via a chest-wall incision without thoracotomy. Pathologic examination showed a benign teratoma containing an immature tooth. PMID- 11191951 TI - [Applied medicine and ophthalmology]. AB - Medicine as applied by specialists is an unexplored territory. By the example of Ophthalmology some relevant, specific scientific problems are outlined here. PMID- 11191952 TI - [Diphtheria antitoxin level 2 years after booster vaccination]. AB - In a prospective, controlled, randomized, multicenter study the immunogenicity of a single (day 0) and two (day 0, 28) booster vaccination against diphtheria were compared in subjects who had received their last diphtheria vaccination more than 10 years ago. Both short-term and long-term immunogenicity was assessed by determining diphtheria antitoxin levels four weeks after vaccination and after one and two years. 102 subjects received the first booster vaccination, and 83 were vaccinated twice. Prior to the first vaccination 27% of the subjects had a diphtheria antitoxin level below 0.01 I.U./ml; after the first booster only 5% were unprotected. The second booster did not show a significant effect, however, in 1 of the 5 subjects who were still unprotected after the first booster the second elicited an antitoxin level of more than 0.01 I.U./ml. After one and two years 7% and 8% of the subjects had diphtheria antitoxin level below 0.01 I.U./ml. A serological effect of a second booster vaccination four weeks after the first one could not be demonstrated neither after one nor after two years. PMID- 11191953 TI - [Induction of oral tolerance: a new therapeutic strategy for autoimmune diseases?]. AB - The phenomenon of oral tolerance (the state of systemic hyporesponsiveness after oral antigen delivery) has been known for a long time, nevertheless it turned out only in the last decades that it could be used for the treatment of autoimmune diseases. The induction of oral tolerance was shown to be very effective for the prevention of disease development in numerous animal models of human autoimmune diseases, and to a lesser extent for the alleviation of symptoms in already ill animals. As opposed to these promising experiments, no such considerable results were found in human trials. In this review. I will try to summarize the present status of these experiments and to discuss the possible advantages and disadvantages of this therapeutic protocol. PMID- 11191954 TI - Nationwide epidemiology of hospitalized patients with first-time traumatic brain injury with special reference to prevention. AB - The national data of hospitalized TBI-patients were gathered retrospectively during the years 1991-95 from the Hospital Discharge Register. The inclusion criteria were: TBI as the primary diagnosis (ICD-9: 800, 801, 803, 850, 851-854), no history of previous TBI during the previous three years and the hospitalization of the patient. The incidence of TBI varied from 4 793-5 055 (95 100 per 100,000 people), comprising altogether 24,497 patients. The biggest subgroups of external cause were the sudden fall (61%) and vehicle accidents (26%). The biggest subgroups of the place of accident were the home (33%) and the traffic area (30%). The data reflect an assumption that many causes of TBI are preventable. PMID- 11191955 TI - [Social vulnerability, social isolation of chronic psychiatric patients]. AB - Social vulnerability and social isolation as to different, light and severe grades of chronically ill psychiatric patients were evaluated. A social vulnerability index, composed out of marital status, income, health, living conditions, occupation, and risk factors in childhood was used. The vulnerability of 64 severely chronically ill patients and of 84 chronically ill patients was assessed. According to their vulnerability, the patients were divided into a group of highly vulnerable and a group of less vulnerable patients. The social isolation of the two groups (severely chronically und chronically ill patients) was compared and assessed. We used objective criteria (such as living alone, no friends, no contact to family members) and subjective criteria (feeling isolated). Social Vulnerability and social isolation are higher in severely chronically ill patients compared to chronically ill patients. The severely sick group is significantly more affected by objective and/or by subjective isolation than the less sick group. In both groups patients have more difficulties in social relationships than non-isolated patients. There is no significant correlation between objective isolation and subjective isolation. PMID- 11191956 TI - [Patulous eustachian tube--diagnosis and therapy]. AB - The patulous Eustachian tube (tuba aperta) is a benign condition that may be overlooked or misdiagnosed. It is a distressing condition for the patient with such symptoms as autophony and a sensation of fullness in the ear. One third of the women with the diagnosis are pregnant or taking oestrogens. The diagnosis is made by the history of fullness or blockage and hearing one's own voice and breath in the ear. The drum is usually atrophic and moves with respiration but this may not be visible. The usual past history is of weight loss. The patulous Eustachian tube is frequently associated with peritubal atrophy, and usually responds to conservative measures such as weight gain. The application of nose drops is wrong. Why some patients with a patulous tube and movement of the drum with respiration have no symptoms and other patients with very bothersome symptoms have so few objective signs and no movement of the drum that can be observed with respiration, remains a mystery. PMID- 11191957 TI - [XXXVI Congress of the French Association for Hand Surgery. Paris, 14-16 December 2000. Abstracts]. PMID- 11191958 TI - Blood, sweat, serious fears. Hepatitis C puts rescue workers' lives at risk and under scrutiny. PMID- 11191959 TI - A new smoking gun? David Kessler unloads on big tobacco's tactics. PMID- 11191960 TI - Male pattern boldness. PMID- 11191961 TI - Organic foods offer peace of mind--at a price. PMID- 11191962 TI - How to beat back a heart attack? With swift and aggressive counterpunching. PMID- 11191963 TI - JRCPL becomes Clinical Medicine. PMID- 11191964 TI - Two blueprints for the future: cancer services in England and Wales. PMID- 11191965 TI - Prevention and treatment of osteoporosis. Clinical guidelines and new evidence. PMID- 11191966 TI - Haemodynamic and ventilatory support in severe sepsis. PMID- 11191967 TI - Empirical choice of antibiotic therapy in sepsis. PMID- 11191968 TI - Sepsis in immunocompromised hosts. PMID- 11191969 TI - Mechanisms and detection of bacteraemia. PMID- 11191970 TI - Disease emergence and health transitions in the last millennium. AB - For most of the first millennium, average expectation of life was only 30 or 40 years. The beginning of the 20th century saw the start of improvements, which by the century's end meant that a baby boy could expect an average 75 years of life, a baby girl even longer. The successes of the 20th century were not products of advances in medicine alone, but consequences of the great sanitary reforms that fuelled the public health movement in late Victorian Britain. However, health challenges also grew and changed: the rise in so-called modern epidemics (coronary heart disease, cancer, accidents and mental illness); the ageing of the population; the containment of the costs of rapid technological advances; the marked and intractable inequalities in health status between rich and poor, and between North and South. The dawn of a new millennium sees many of these health problems carried over from the late 20th century, whilst communicable diseases, once thought conquered, continue to pose a serious threat to human health because of their global significance. This paper traces progress in the health of the population and identifies some of the key challenges for medicine in the 21st century. PMID- 11191971 TI - Will medicine be revolutionised by genomics? PMID- 11191972 TI - What proportion of dyspeptic patients having H. pylori breath test subsequently undergo endoscopy? AB - BACKGROUND: Helicobacter pylori (HP) testing in young patients with uncomplicated dyspepsia has been recommended. A test and treat strategy for dyspeptics positive for HP is recommended by the European H. pylori Study Group and the American Gastroenterology Association. OBJECTIVES: To assess the rates of re-referral for upper GI endoscopy (OGD) and outpatient (OPD) attendance in uncomplicated dyspeptic patients following assessment of HP status. METHODS: 190 patients under 50 years of age with uncomplicated dyspepsia (without alarm symptoms) referred from general practitioners (GPs) to the gastroenterology department underwent HP urea breath test (UBT). GPs were informed of the results of UBT and recommended eradication therapy if positive, and if negative advised symptomatic treatment with an acid suppressant with/without a prokinetic. The patients were analysed for subsequent attendance at OGD or OPD in the following two years. RESULTS: HP was present in 93 of 190 patients. Twenty of 190 (10.5%) patients subsequently were re-referred and underwent OGD for continuing dyspeptic symptoms; a further 6 were seen in OPD but not endoscoped as they have been judged to have uncomplicated gastro-oesophageal reflux disease. At time of OGD all patients were negative on Campylobacter-like organism (CLO) test for HP. Findings at OGD were normal (9), hiatus hernia (6), gastritis (4) and duodenitis (1). No case of peptic ulcer disease or gastric cancer has been identified. CONCLUSIONS: In this group of dyspeptic patients, adopting a test and treat policy after initial analysis of HP resulted in 10.5% being re-referred for subsequent OGD; findings in those endoscoped were normal or minimal. A test and treat strategy for H. pylori in uncomplicated dyspeptics therefore saves endoscopies and outpatient consultations without missing significant underlying pathology. PMID- 11191973 TI - Attachments in public health for physicians. AB - Hospital-based specialist registrars in Nottingham are offered six month secondments in public health medicine. These attachments give clinicians valuable skills in public health and an opportunity to influence the development of local health service provision. Other skills gained are an understanding of the balance between health promotion and disease treatment; the management of limited resources; an appreciation of the effects of social deprivation; the chairing and preparing of committee meetings; and contact tracing of communicable diseases. We strongly recommend the experience gained from working in a lively public health department. PMID- 11191974 TI - Who gets alcoholic liver disease: nature or nurture? AB - The factors determining why fewer than 10% of drinkers develop advanced alcoholic liver disease remain largely unknown. There is a weak relationship between disease risk and the dose and pattern of alcohol consumed. Obesity increases the risk of all stages of alcoholic liver disease, probably reflecting the role of steatosis in the pathogenesis of more advanced disease. Women develop disease at a lower intake than men due, in part, to their lower volume of distribution for alcohol, but also potentially to increased gut permeability to endotoxin. Recent studies suggest a non-gender-linked genetic component to disease susceptibility and recent case-control studies have suggested that polymorphisms of genes encoding cytokines and other immunoregulatory molecules may exert a significant effect. The pattern of polymorphisms associated with risk suggests that antibody mediated mechanisms play a role in disease pathogenesis. This has implications for treatment and for identifying high risk individuals at an early stage. PMID- 11191975 TI - Brains and minds: a brief history of neuromythology. PMID- 11191976 TI - Science, society and the perplexed physician. AB - In a time of changing attitudes to science and medicine, Lord Turnberg asks whether there is a future for the physician. The population has never been healthier, but, paradoxically, the public seems to be more afraid then ever of death and illness. As more information becomes available in the public arena, anxious patients want certainty when choices almost always have to be offered in the absence of certainty. The author speculates that in this brave new world the need for physicians will increase rather than the reverse. However, physicians must recognise that effective communication, empathy, and compassion are as essential to their role as scientific knowledge and understanding. PMID- 11191977 TI - Drug and alcohol abuse: what physicians need to know. PMID- 11191978 TI - Modern doctoring. PMID- 11191979 TI - Health care practitioners? PMID- 11191980 TI - Controversy in thyroid disease. PMID- 11191981 TI - Controversy in thyroid disease. PMID- 11191982 TI - Controversy in thyroid disease. PMID- 11191983 TI - Bellmanism: the distortion of reason. PMID- 11191984 TI - Single consultation cerebrovascular disease clinic. PMID- 11191985 TI - Virus hepatitis update. PMID- 11191986 TI - SmithKline Beecham halts tests of lotrafiban, an oral glycoprotein IIb/IIIa inhibitor. PMID- 11191987 TI - More than a journal. PMID- 11191988 TI - Planetary science. Jupiter's two-faced Moon, Ganymede, falling into line. PMID- 11191990 TI - Germany. Chipping away at feudal vestiges in academe. PMID- 11191989 TI - Embryo research. British Parliament approves new rules. PMID- 11191991 TI - Malaria. Old movie spawns a new discovery. PMID- 11191992 TI - Cancer research. Preventing hair loss from chemotherapy. PMID- 11191994 TI - Brazil. Society seeks legislative aide fellow. PMID- 11191995 TI - Medical research. NIH kills deal to upgrade heart data. PMID- 11191993 TI - Evolution. Tooth theory revises history of mammals. PMID- 11191996 TI - Astrophysics. Ravenous black holes never say diet. PMID- 11191997 TI - India. Scientist restored to top agriculture post. PMID- 11191998 TI - Japan. Superagency seeks to reconcile two cultures. PMID- 11191999 TI - Policy. NASA's street fighter takes on tangled space science program. PMID- 11192001 TI - Archaeology. Japanese fraud highlights media-driven research ethic. PMID- 11192000 TI - 2001 U.S. budget. Record year for science, but can it be repeated? PMID- 11192002 TI - Pharmacology. How the body's 'garbage disposal' may inactivate drugs. PMID- 11192003 TI - Pharmacology. A worrisome side effect of an antianxiety remedy. PMID- 11192004 TI - Priorities in HIV prevention. PMID- 11192005 TI - Priorities in HIV prevention. PMID- 11192006 TI - Helminthic infection and HIV vaccine trials. PMID- 11192007 TI - That's no worm... PMID- 11192008 TI - Biology and music. The music of nature. PMID- 11192009 TI - Biology and music. Music of the hemispheres. PMID- 11192010 TI - Chemistry. Switched-on nickel. PMID- 11192011 TI - Astronomy. Orion sheds new light on star and planet formation. PMID- 11192012 TI - Paleoclimate. Climate change across the hemispheres. PMID- 11192014 TI - Microquasars raise megaquestions. PMID- 11192013 TI - Bursts, rays, and jets. PMID- 11192015 TI - Astronomical odd couple? Or alter egos? PMID- 11192016 TI - Tatars' saucy project takes on the world. PMID- 11192017 TI - Keeping the beat in a noisy world. PMID- 11192018 TI - A fluorescent reporter assay for the detection of ligands acting through Gi protein-coupled receptors. AB - Accompanying the advances in basic biology of G protein-coupled receptors (GPCRs) is the practical need among biopharmaceutical companies for sensitive assays to assess GPCR function, particularly formats that are compatible with high throughput drug screening. Here we describe a novel cell-based assay format for the high-throughput detection of ligands for Gi protein-coupled receptors. Two Gi GPCRs, mu-opioid receptor (mu-OPR) and 5-hydroxytryptamine receptor la (5HT1aR) are employed as model receptor targets. The key feature of this assay system is the isolation of stable, clonal Chinese hamster ovary (CHO) cell lines that carry three separate expression plasmids: (1) a chimeric Gq/i5 protein (which re directs a negative Gi-type signal to a positive Gq-type response), (2) a given Gi GPCR, and (3) a beta-lactamase (beta1a) reporter gene responsive to Gi-GPCR signaling. Cell-based assays built using this format show appropriate rank order of potency among a reference set of receptor agonist and antagonist compounds. Such assays are also robust, reliable, and can be used for industrial-scale applications such as high-throughput screening for drug leads. PMID- 11192019 TI - Angiotensin antagonists. PMID- 11192020 TI - Receptor-dependent regulation of [Ca2+]i and phospholipase C in vascular endothelial cells. PMID- 11192021 TI - High-altitude pulmonary hypertension and signal transduction in the cardiovascular system. PMID- 11192022 TI - Penicillin binding proteins, beta-lactams, and lactamases: offensives, attacks, and defensive countermeasures. AB - A strong outer covering of peptidoglycan (the sacculus) is essential for most bacteria. Beta-lactams have evolved billions of years ago and can block saccular growth of the organism. This led to the evolution of beta-lactamases and resistant penicillin binding proteins (PBPs). With the introduction of lactam antibiotics by the pharmaceutical industry, resistance genes in nature were laterally transferred to antibiotic-treated disease-causing organisms and additional modification of beta-lactamase genes and of the regulatory genes of the mecA region took place. However, it can be concluded that very little of either type of resistance mechanisms represents new basic evolution against the penicillin type antibiotics. In the last 60 years the resistant bacteria in the main arose by movement of genes from other organisms, from minor genetic changes, and from alteration of the regulation of synthesis. PMID- 11192023 TI - Chemistry and microbiology of permeable reactive barriers for in situ groundwater clean up. AB - Permeable reactive barriers (PRBs) are receiving a great deal of attention as an innovative, cost-effective technology for in situ clean up of groundwater contamination. A wide variety of materials are being proposed for use in PRBs, including zero-valent metals (e.g., iron metal), humic materials, oxides, surfactant-modified zeolites (SMZs), and oxygen- and nitrate-releasing compounds. PRB materials remove dissolved groundwater contaminants by immobilization within the barrier or transformation to less harmful products. The primary removal processes include: (1) sorption and precipitation, (2) chemical reaction, and (3) biologically mediated reactions. This article presents an overview of the mechanisms and factors controlling these individual processes and discusses the implications for the feasibility and long-term effectiveness of PRB technologies. PMID- 11192024 TI - Baggasse preservation: a need for a biotechnological approach. AB - Paper is one of the basic needs of modern life. With the consumption of paper likely to grow to 320 million MT by the year 2001, the the worldwide pulp and paper industry is gradually realizing that there is a shortage of the traditional raw material of cellulosic fiber. Bagasse--a byproduct of the sugar industry, presents a potential source of fiber for the paper industry without further compromising the environmental concern. It is cheap, perennially replenishible, presently does not have an alternative economically attractive value added usage, and has adequate chemical and mechanical properties for paper making. However, for it to be available to the paper industry throughout the year, it needs to be stored and preserved for a period of 6 to 8 months. With inherent problems associated with bagasse morphology, intricacies reflected as a result of its physicochemical characteristics, army of microbial infestants, cost-effective quality expectations of the paper industry, and the ecofriendly approach demanded by the society/pollution control boards/environmentalists, there does not seem to be any viable alternative except to use biotechnology approaches for bagasse preservation. It envisages the preservation of maximally depithed bagasse in the piles/heaps, using one-time fine misting of a preservative formulation comprised of biodegradable and nondegradable chemicals inhibiting the microbial population at selected enzyme levels. Its efficacy is improved by open, dry, windy, and moderate sunlit sites for storage. The method is simple, sustainable, and superior to the prevalent methods that are cost, capital, and energy intensive, non-eco-friendly and have adverse cost:benefit ratios. The biotechnology approach has an inherent scope for further optimization, automation, and economization. PMID- 11192025 TI - Control of foodborne pathogens during sufu fermentation and aging. AB - Control of the foodborne pathogens Escherichia coli O157:H7, Salmonella typhimurium, Staphylococcus aureus, and Listeria monocytogenes during sufu fermentation was evaluated. Before fermentation, pathogens were inoculated onto tofu (substrate for sufu) at 5 log cfu/g or 3 log cfu/g, and starter culture (Actinomucor elegans) was inoculated at 3 log cfu/g. After 2 days of fermentation at 30 degrees C, the four pathogens reached 7 to 9 log cfu/g, and the mold count reached 6 to 7 log cfu/g. After fermentation, sufu samples were aged in a solution of 10% alcohol + 12% NaCl. After 1 month of aging, the total bacterial count was 6 to 7 log cfu/g, but all foodborne pathogens and mold were reduced to nondetectable levels. The total bacterial count decreased after aging for 2 months and 3 months, but the differences were not significant (P > 0.05) compared with the count after 1 month. Microorganism in experimental sufu from different aging periods and in commercial sufu were compared. A total of 270 isolates were purified and identified by the BBL Crystal Identification System. From the experimental sufu samples, 49 Bacillus spp. (20.4%), 167 Enterococcus spp. (69.6%), 6 Shewanella putrefaciens (2.4%), and 18 miscellaneous gram-negative bacilli (7.5%) were identified. From commercial sufu samples, 17 Bacillus spp. (56.7%), 2 Enterococcus durans (6.7%), 5 miscellaneous gram-negative bacilli (16.7%), 5 Corynbacterium aquaticum (16.7%), and 1 Shewanella putrefaciens (3.3%) were obtained. Although the longer aging period did not significantly decrease the total bacterial count, it may help in the development of sufu flavor. This study showed that sufu fermentation and aging can control common foodborne pathogens, so sufu is a safe product even though its preparation does not include pasteurization. PMID- 11192026 TI - Lycopene in tomatoes: chemical and physical properties affected by food processing. AB - Lycopene is the pigment principally responsible for the characteristic deep-red color of ripe tomato fruits and tomato products. It has attracted attention due to its biological and physicochemical properties, especially related to its effects as a natural antioxidant. Although it has no provitamin A activity, lycopene does exhibit a physical quenching rate constant with singlet oxygen almost twice as high as that of beta-carotene. This makes its presence in the diet of considerable interest. Increasing clinical evidence supports the role of lycopene as a micronutrient with important health benefits, because it appears to provide protection against a broad range of epithelial cancers. Tomatoes and related tomato products are the major source of lycopene compounds, and are also considered an important source of carotenoids in the human diet. Undesirable degradation of lycopene not only affects the sensory quality of the final products, but also the health benefit of tomato-based foods for the human body. Lycopene in fresh tomato fruits occurs essentially in the all-trans configuration. The main causes of tomato lycopene degradation during processing are isomerization and oxidation. Isomerization converts all-trans isomers to cis isomers due to additional energy input and results in an unstable, energy-rich station. Determination of the degree of lycopene isomerization during processing would provide a measure of the potential health benefits of tomato-based foods. Thermal processing (bleaching, retorting, and freezing processes) generally cause some loss of lycopene in tomato-based foods. Heat induces isomerization of the all-trans to cis forms. The cis-isomers increase with temperature and processing time. In general, dehydrated and powdered tomatoes have poor lycopene stability unless carefully processed and promptly placed in a hermetically sealed and inert atmosphere for storage. A significant increase in the cis-isomers with a simultaneous decrease in the all-trans isomers can be observed in the dehydrated tomato samples using the different dehydration methods. Frozen foods and heat sterilized foods exhibit excellent lycopene stability throughout their normal temperature storage shelf life. Lycopene bioavailability (absorption) can be influenced by many factors. The bioavailability of cis-isomers in food is higher than that of all-trans isomers. Lycopene bioavailability in processed tomato products is higher than in unprocessed fresh tomatoes. The composition and structure of the food also have an impact on the bioavailability of lycopene and may affect the release of lycopene from the tomato tissue matrix. Food processing may improve lycopene bioavailability by breaking down cell walls, which weakens the bonding forces between lycopene and tissue matrix, thus making lycopene more accessible and enhancing the cis-isomerization. More information on lycopene bioavailability, however, is needed. The pharmacokinetic properties of lycopene remain particularly poorly understood. Further research on the bioavalability, pharmacology, biochemistry, and physiology must be done to reveal the mechanism of lycopene in human diet, and the in vivo metabolism of lycopene. Consumer demand for healthy food products provides an opportunity to develop lycopene-rich food as new functional foods, as well as food-grade and pharmaceutical-grade lycopene as new nutraceutical products. An industrial scale, environmentally friendly lycopene extraction and purification procedure with minimal loss of bioactivities is highly desirable for the foods, feed, cosmetic, and pharmaceutical industries. High-quality lycopene products that meet food safety regulations will offer potential benefits to the food industry. PMID- 11192027 TI - Endoscopic excision of benign tumors in the forehead and brow. AB - Twenty-five cases of benign tumor of the forehead and brow were excised successfully with endoscope-assisted surgery. The access incision was selected strategically behind the front hairline. For tumors in the middle of the forehead, the tumor was approached by subgaleal dissection. For those in the brow or temporal area, the dissection plane was just superficial to the deep temporal fascia. Patient age ranged from 3 to 59 years. The mass varied in size from 1.0 x 0.5 to 2.0 x 2.0 cm. There were 18 lipomas, 6 dermoid cysts, and 1 pilomatricoma. There was no residual mass or recurrence 1 to 24 months postoperatively. There was no paresthesia or numbness in the scalp. Patients and their families were greatly satisfied with this operation and the absence of visible scarring. PMID- 11192028 TI - Operative management of neuromatous knee pain: patient selection and outcome. AB - The management of intractable knee pain secondary to neuromata continues to be optimized. Forty-three patients with intractable knee pain were studied prospectively. Consideration for this procedure requires pain of at least a 1 year duration, failure of conservative management, pain localization at a Tinel's point, and at least a 5-point reduction of pain on a visual analog scale after nerve blockade with 1% lidocaine. Thirty patients met the criteria for the procedure and 25 patients underwent the procedure. Mean patient age was 50.3 years and mean duration of pain was 6.6 years. Pain etiology included total knee replacement in 10 patients and trauma in 15 patients. Mean number of prior operations on the knee was 5.1. Sixty-two nerves were excised in the 25 patients, including the infrapatellar branch of the saphenous nerve (N = 24), the tibiofibular branch of the peroneal nerve (N = 5), the medial retinacular nerve (N = 12), the lateral retinacular nerve (N = 8), the medial cutaneous nerve (N = 6), the anterior cutaneous nerve (N = 3), and the lateral femoral cutaneous nerve (N = 4). Complete pain relief was obtained in 11 patients (44%). Partial pain relief was reported in 10 patients (40%). No pain relief was reported in 4 patients (16%). Follow-up ranged from 1 to 4 years. Selective denervation for neuromatous knee pain is beneficial in select patients. Patient satisfaction was 84% (21 of 25 patients) after the procedure. No patient was made worse. PMID- 11192029 TI - A rationale for adjuvant surgical intervention in pyoderma gangrenosum. AB - Medical specialists who care for patients with pyoderma gangrenosum have been reluctant traditionally to consult plastic surgeons. This is the result of previous negative experience with debridement and skin grafting. However, a new understanding of the pathophysiology of the disease process, and better therapeutic options for control have emerged. Very few studies report the results of surgical therapy of this disease, and fewer yet report successful outcome. The authors present their limited experience at the American University of Beirut with 4 patients who were controlled medically followed by skin grafting their large wounds, thus decreasing their morbidity and hospital stay. A review of the literature together with insights on the rationale and timing of surgery in this particular small group of patients are discussed. PMID- 11192030 TI - Etiology and pathogenesis of aponeurotic blepharoptosis. AB - How and why aponeurotic blepharoptosis develops was investigated in terms of the relationship between the levator aponeurosis and Mueller's muscle functioning as the muscle spindle of the levator muscle. A total of 200 consecutive patients with moderate to severe acquired blepharoptosis completed questionnaires regarding their history of physical irritations to the eyelids, and intraoperative conditions of the levator aponeurosis and Mueller's muscle were evaluated. Several kinds of physical irritations to the eyelids were reported, such as habitual rubbing of the eyelids, contact lens usage, cataract surgery, and continuous rubbing of the eyelids while crying all night. The two main findings for aponeurosis were that it was disinserted from the tarsus, resulting in a large amount of play between the aponeurosis and the tarsus, and that the aponeurosis and Mueller's muscle were attenuated and elongated. The authors believe that rubbing may have caused disinsertion as well as attenuation and elongation of the aponeurosis, which result in transmission failures between the levator muscle and the tarsus as well as between the levator muscle and the mechanoreceptor of Mueller's muscle, leading to clinical blepharoptosis. PMID- 11192031 TI - A primary burn wound does not slow the contraction rate of an adjacent excisional wound. AB - The response to major burn injury includes systemic release of mediators that may have an effect on wound healing. The authors evaluated the effect of a burn injury on the contraction of an excisional wound adjacent to the burn, and the effect of plasma derived from burn-injured animals on the contraction of the fibroblast-populated collagen matrix (FPCM). Nine rats (90-100 days old) under anesthesia received a standardized 40% total body surface area burn to the dorsum, and eight rats (controls) were sham burned. Immediately thereafter all animals had a square (2.25 cm2) of unburned dermis excised from the dorsum, superior to the burn wound. The excisional wound area was measured at 2 to 3-day intervals postoperatively. Plasma was collected from some animals on postburn day 15; the contraction-stimulating ability of burn vs. control plasma was measured in the FPCM. All animals remained free of sepsis. The excisional wound area in all animals decreased to 50% and then 25% of the initial area after approximately 4 and 8 days respectively. The rate of wound contraction (i.e., wound area reduction) did not differ between burn and control animals. Contraction stimulated by 5% plasma in the FPCM (expressed as a percentage of the original matrix area) was 70.2+/-6.4 (standard deviation) mm2 vs. 62.4 +/-3.9 mm2 for burn vs. control rats respectively (p>0.05). Burn injury in this model did not alter the contraction of an excisional wound at an unburned site. There was no significant difference in the contraction-stimulating ability (FPCM model) of plasma from the burned rats compared with plasma from unburned control rats. Burn injury appears to have an inconsequential effect on the contraction of an adjacent wound. PMID- 11192032 TI - Madelung's disease: case report and discussion of treatment options. AB - Madelung's disease was first described in 1846. Since then, approximately 200 patients have been reported in the literature. Its three main characteristics typical location of the lesions, symmetry, and the diffusive nature of the fat are more often found in men of Mediterranean descent. A clear association with alcohol abuse is reported, but the etiology remains uncertain. Patients usually complain of their cosmetic appearance, but treatment can be rendered for decreased neck motion and/or aerodigestive problems. Given the benign nature of the lesion, surgical debulking is the treatment of choice, with liposuction reserved for smaller lesions. A standard facelift pattern can be used for skin incisions and removal, with good cosmetic results. PMID- 11192033 TI - Infusion port dislodgement of bilateral breast tissue expanders after MRI. AB - Tissue expanders are placed routinely for breast reconstruction, and magnetic resonance imaging (MRI) is a common diagnostic procedure. Many studies have reported on the safety of MRI in patients with nonferromagnetic implants; however, many tissue expanders contain ferromagnetic components. The authors present a case of bilateral tissue expander infusion port dislodgment after MRI. A 56-year-old woman underwent bilateral mastectomy and immediate reconstruction with McGhan BIOSPAN tissue expanders. These implants contain integral nonferromagnetic infusion ports, as well as small, powerful Magna-Site magnets. Several weeks postoperatively the patient underwent MRI of her spine, which was ordered by her primary physician for back pain. Subsequently, the infusion ports could not be located with the finder magnet. A chest radiograph was obtained, which demonstrated bilateral dislodgment of the infusion ports. Surgical removal and replacement of the tissue expanders were required. Safety considerations of MRI have been discussed extensively in the literature, and data on MRI with various implanted devices have been obtained. The potential risks of performing MRI on patients with metallic implants include conduction of electrical currents, heating of the implant, misinterpretation resulting from artifact, and the possibility of movement or dislodgment of the implant. The small magnet integral to many tissue expanders may be overlooked by patients and physicians during pre MRI screening. All patients undergoing tissue expansion with implants that contain integral ports should be thoroughly warned about the potential hazards of MRI. PMID- 11192034 TI - Negative-pressure dressings in the treatment of hidradenitis suppurativa. AB - Negative-pressure dressings have been used in the treatment of a variety of open wounds, and as a bolster for skin grafts. The benefits of these dressings include increased oxygen tension in the wound, decreased bacterial counts, increased granulation formation, and the prevention of shear force on wounds. Also, by virtue of the diminished need for daily dressing changes, there are the additional advantages of enhancing patient comfort, decreasing nursing work, and diminished cost of wound care. Hidradenitis suppurativa (HS) is a chronic infection of the apocrine sweat glands. Treatment options range from oral isotretinoin to radical excision. Wound closure may be achieved by secondary intention, skin grafting, or flap closure. Complications may still arise and include disease progression and squamous cell carcinoma. Radical excision yields the best results in terms of disease eradication. The authors describe using the negative-pressure dressing in two cases of bilateral axillary HS to secure skin grafts firmly to the wound bed after radical excision of all involved tissues. Patient comfort and acceptance was high, and skin graft take was excellent. The dressings themselves are simple to apply and are highly effective. PMID- 11192035 TI - Bilateral, extended V-Y advancement flap. AB - A modification of the V-Y advancement flap for the closure of circular skin defects is presented to decrease the tension in the closure and to break the midline vertical scar. Bilateral, extended V-Y advancement flaps with additional limbs extending to the advancing edges of the standard flaps were marked on both sides of the wound. After advancement of the V-Y flaps on their subcutaneous pedicle, the upper and lower extensions were hinged downward as transposition flaps to close the middle portion of the circular defect, where maximum tension occurs. This procedure was applied to 10 patients with sacral and trochanteric pressure sores. No complications or recurrences were noted during the 2 to 10 months of follow-up. Bilateral, extended V-Y advancement flaps enable the reconstruction of large defects without midline tension. Also, the resulting scar where the flaps meet is a zigzag line, so a straight midline scar is avoided. PMID- 11192036 TI - Split gluteus maximus island flaps for concomitant closure of ischial and sacral pressure sores. AB - The author presents an innovation in the use of the gluteus maximus musculocutaneous flap that allows one to repair both sacral and ischial pressure sores concomitantly in a paraplegic patient. The musculocutaneous unit is divided into superior and inferior halves, each of which is supplied by their respective gluteal arteries. The "islanded" flaps can be moved in different directions independent of one another to cover both the sacral and ischial regions at the same time. The donor area can be closed primarily. Three patients were operated using this method. The 1-year follow-up of 1 patient is presented. PMID- 11192037 TI - Actinomycosis of the frontal and parotid regions. AB - Cervicofacial actinomycosis still occurs infrequently and should be included in the differential diagnosis of neoplasms, and chronic suppurative and granulomatous lesions of the head and neck region. The authors present two cases of actinomycosis. Patient 1 was a 32-year-old man who was first seen with a firm, suppurative mass at his left frontal region. Patient 2 was a 36-year-old woman with an indurated mass at her left parotid area. Both patients were diagnosed histopathologically with cervicofacial actinomycosis, but each patient had a different clinical course and different response to antimicrobial and surgical treatments. PMID- 11192038 TI - Malignant melanoma in a burn scar. AB - Cancers of various sorts are occasionally encountered in burn scars. These lesions are usually squamous cell carcinomas, and the burn scars are usually old. Very rarely, malignant melanoma is encountered. An 87-year-old nursing home patient who had been burned by a lightening strike at age 16 was evaluated. She had sustained a wound covering 2% or 3% of her body surface involving her neck and the upper portion of her anterior trunk that had required several grafts. A lesion was noted over the suprasternal notch approximately 3 months before admission. The biopsy was reported as malignant melanoma. She was subsequently treated by wide reexcision with an associated Z-plasty for neck release. Because of the patient's age and the presence of four areas of regional lymph nodes nearby into which metastasis might spread, no lymph node dissections were carried out. The specimen from the reexcision was reported as squamous cell carcinoma in situ, melanoma in situ, and multinucleated giant cell reaction, acute and chronic infiltrates. The wound margins were clear. PMID- 11192039 TI - Infantile myofibromatosis: case report of a solitary hand lesion with emphasis on differential diagnosis and management. AB - Infantile myofibromatosis, both solitary and multicentric types, is discussed with emphasis on the importance of diagnosing this condition correctly. Its distinctive clinical and histological characteristics are described, as are the hazards of overhasty and overly ambitious surgical intervention. Other similarly presenting fibromatous diseases of infancy and childhood are discussed, including aplasia cutis, infantile fibrosarcoma, recurring infantile digital fibromatosis, and juvenile aponeurotic fibromatosis. A case of infantile myofibromatosis, solitary type, is reported, and the two surgical procedures carried out over a 4 year period are described. The importance of histological and immunohistochemical evaluation of lesions present during the neonatal period is stressed. PMID- 11192040 TI - Posttraumatic epidermal inclusion cyst of the deep infratemporal fossa. AB - The authors report a case of an epidermal inclusion cyst found in the deep infratemporal fossa 12 years after the patient sustained blunt trauma to that region. Posttraumatic epidermal inclusion cysts are rare and occur mainly in the fingers, palms, and soles. Introduction of the epidermal elements into the dermis during the trauma is thought to be the cause. This case is rare in presentation, with few reports in the English literature that describe an epidermal inclusion cyst in the deep infratemporal fossa. Review of the English literature disclosed no other cases of epidermal inclusion cyst after blunt trauma involving the deep infratemporal region. PMID- 11192041 TI - Fires and burns during plastic surgery. AB - Many plastic surgery procedures are performed under local anethesia. When the procedure involves the head and neck, oxygen is perilously close to the surgical field. A thorough understanding of the fire triangle will allow the plastic surgeon to develop a routine that will avoid any risk of fire. The fire triangle consists of a heat source, a fuel, and an oxidizer. By removing one component of the fire triangle, the risk of fire is averted. An in-depth look at each component is needed because fire hazards involve some surprising sources. PMID- 11192042 TI - Modified mandibulotomy approach to tumors of the oropharynx. AB - The surgical approach to tumors in the deep oral cavity, oropharynx, and parapharyngeal space has always been a problem. Midline mandibulotomy for exposure and resection of tumors in these areas is usually essential. However, postoperatively accurate and stable reconstruction of the symphysis is difficult. The authors present a modified notch mandibulotomy in a trapezoidal shape to stabilize the symphysis with only a four-hole miniplate. This shape of the osteotomy reduces the time to return to an unrestricted diet and permits more accurate occlusion. PMID- 11192043 TI - The other art-and-science. PMID- 11192044 TI - Adrenal incidentaloma as a cause of postoperative exaggerated ecchymosis. PMID- 11192045 TI - Ulnar tunnel syndrome secondary to lipoma of the hypothenar region. PMID- 11192046 TI - Bilateral lower extremity thrombosis in a patient with protein S deficiency. PMID- 11192047 TI - Use of circular subcutaneous tissue flaps to prevent fistulas in urethroplasty. PMID- 11192048 TI - Split-thickness skin graft donor site dressing: preliminary results of a controlled, clinical comparative study of MEBO and Sofra-Tulle. PMID- 11192049 TI - Innervated dorsal adipofascial turnover flap for fingertip amputations. AB - Traumatic or thermal injury to the fingertip may result in composite tissue loss. Exposed tendon, bone, or joint surface is best treated by flap coverage. The authors present their experience with a new technique that provides coverage for fingertip defects using the innervated dorsal adipofascial turnover flap, which consists of adipofascial tissue only and relies on the arterial anastomotic network of this tissue layer to sustain its vascularization. Eight digital amputations between the distal phalanx proximal to the nail matrix and midportion of the middle phalanx were resurfaced successfully with the innervated dorsal adipofascial turnover flap. The flaps survived completely; the mean follow-up was 9 months. This technique seems to be a relatively simple way of achieving early recovery. It does not require the use of distant flap immobilization of adjacent digits, nor does it require the use of homodigital flaps, which may jeopardize an already injured finger. The main advantages of the innervated dorsal adipofascial turnover flap are its ready availability from the local tissue, its sensation, and the absence of functional and aesthetic disturbance at the donor site. PMID- 11192050 TI - Changes in the elastic properties of tendon structures following 20 days bed-rest in humans. AB - The purpose of this study was to investigate the effects of 20 days bed-rest on the elastic properties of tendon structures of the human knee extensor muscles in vivo. Six healthy men carried out a 6 degrees head-down bed-rest for 20 days. Muscle volume and maximal voluntary contraction (MVC) torque of the quadriceps femoris muscle significantly decreased by an average of 7.8 (SD 2.7)% and 14.9 (SD 6.9)%, respectively. Before and after bed-rest, the elongation (l) of the tendon and aponeurosis of vastus lateralis muscle was measured directly by ultrasonography, while the subjects performed ramp isometric knee extension up to MVC. The extent of l tended to be greater after bed-rest. The l above 110 N was significantly greater after bed-rest. Furthermore, the mean stiffness after bed rest [35.5 (SD 7.8) N x mm(-1)] was significantly lower than that before bed-rest [52.6 (SD 19.2) N x mm(-1)]. The rate of torque development significantly reduced after bed-rest by an average of 47%, and the bed-rest induced a lengthening in the electromechanical delay (mean 21%). These results suggest that bed-rest results in a decrease in the stiffness of tendon structures with a reduction of muscle strength and volume. These adaptations of the tendon structures to bed rest would bring about the changes in electromechanical delay and rate of torque development. PMID- 11192051 TI - A comparison of resistance and aerobic training for mass, strength and turnover of bone in growing rats. AB - To determine the effects of resistance versus aerobic exercise on the mass, strength and turnover of bone. thirty Sprague Dawley rats (4 weeks of age) were assigned to one of three experimental groups: sedentary, running or jumping. In the jumping group, the trunk was kept upright during electrically stimulated jumping exercise for 1 h every other day. The running rats ran at speeds of 24 m/min for 1 h every other day. After 4 weeks, the jumping rats exhibited increases in the mass and strength of the lumbar vertebrae and of the mid diaphysis of the femur (mid-femur), and increases in the cross-sectional morphology of these bones: the trabecular bone volume per bone surface, the trabecular thickness, the trabecular bone formation rate per bone surface (BFR/BS). In addition, they exhibited reduced trabecular separation and the area of osteoclast surface per bone surface. The running and sedentary rats showed no such changes. With regard to the mid-femur, in both the jumping and running rats the periosteal BFR/BS was increased. However, only the jumping rats showed a reduction in the BFR/BS at the endocortical surface. These results suggest that resistance exercise accelerates cortical drift and increases the bone mass and strength by stimulating bone formation more efficiently than does aerobic exercise. PMID- 11192052 TI - The use of magnetic resonance images to investigate the influence of recruitment on the relationship between torque and cross-sectional area in human muscle. AB - The purpose of the present study was to investigate the effect of recruitment on the relationship between peak torque and physiological cross-sectional area (PCSA) in human muscle. A group of 11 healthy men participated in this study. Isokinetic knee extension torques at seven (0, 30, 60, 120, 180, 240, and 300 degrees x s(-1)) velocities were determined. Magnetic resonance imaging (MRI) was performed to calculate PCSA of right quadriceps femoris (QF) muscle. Exercise induced contrast shifts in spin-spin relaxation time (T2)-weighted MRI were taken at rest and immediately after repetitive knee-extension exercise and T2 of QF were calculated. The MRI pixels with T2 values more than 1 SD greater than the means at rest were considered to represent QF muscle that had contracted. The area of activated PCSA within the total in QF was expressed as percentage activated PCSA and used as an index of muscle recruitment. The PCSA correlated with peak torque at 0 degree x s(-1) (r = 0.615, P<0.05); in contrast, activated PCSA correlated with peak torque at 120 degrees x s(-1) (r = 0.603, P<0.05) and 180 degrees x s(-1) (r = 0.606, P<0.05). Additionally, there was a significant difference in correlation coefficients between the activated PCSA-peak torque relationship and the PCSA-torque relationship (P<0.05). These results suggested that muscle recruitment affects the PCSA-torque relationship. PMID- 11192053 TI - Effects of breathing control on cardiocirculatory modulation in Caucasian lowlanders and Himalayan Sherpas. AB - This study was performed to investigate the influence of breathing control on the autonomic cardiac regulation at high altitude in adapted and non-adapted awake subjects. We recorded electrocardiogram and pulse oximetry in 14 short-term acclimatized lowlanders and 14 Himalayan Sherpas during resting conditions at an altitude of 5,050 m. Spectrum analysis was performed on synchronized 15 min periods of R-R intervals and the oxygen saturation of arterial blood (SaO2). Despite mean SaO2 being similar in lowlanders and Himalayan Sherpas [78.5 (SD 7.0)% compared to 79.4 (SD5.8)%, respectively], fluctuations in SaO2 were significantly increased in lowlanders compared to Sherpas, thus indicating an unstable regulation of respiration control in lowlanders. Regression analysis demonstrated a significant relationship between spectrum power of SaO2 and the relative power of R-R intervals in the frequency band between 0.01 and 0.08 Hz in lowlanders, but not in Sherpas. Our results demonstrate differences in respiratory and autonomic cardiac control between non-adapted lowlanders and Himalayan high-altitude residents and indicate that unstable breathing control during chronic hypobaric hypoxia is significantly correlated with the autonomic cardiocirculatory regulation. PMID- 11192054 TI - Energy cost of front-crawl swimming at supra-maximal speeds and underwater torque in young swimmers. AB - The energy cost of front-crawl swimming (Cs, kJ x m(-1)) at maximal voluntary speeds over distances of 50, 100, 200 and 400 m, and the underwater torque (T') were assessed in nine young swimmers (three males and six females; 12-17 years old). Cs was calculated from the ratio of the total metabolic energy (Es, kJ) spent to the distance covered. Es was estimated as the sum of the energy derived from alactic (AnA1), lactic (AnL) and aerobic (Aer) processes. In turn, AnL was obtained from the net increase of lactate concentration after exercise, AnA1 was assumed to amount to 0.393 kJ x kg(-1) of body mass, and Aer was estimated from the maximal aerobic power of the subject. Maximal oxygen consumption was calculated by means of the back-extrapolation technique from the oxygen consumption kinetics recorded during recovery after a 400-m maximal trial. Underwater torque (T' x N x m), defined as the product of the force with which the feet of a subject lying horizontally in water tends to sink times the distance from the feet to the center of volume of the lungs, was determined by means of an underwater balance. Cs (kJ x m(-1)) turned out to be a continuous function of the speed (v, m x s(-1)) in both males (Cs = 0.603 x 10(0.228v), r2 =0.991; n = 12) and females (Cs = 0.360 x 10(0.339r), r2 = 0.919; n = 24). A significant relationship was found between T' and Cs at 1.2 m x s(-1); Cs = 0.042T' + 0.594, r = 0.839, n = 10, P<0.05. On the contrary, no significant relationships were found between Cs and T' at faster speeds (1.4 and 1.6 m x s( 1)). This suggests that T' is a determinant of Cs only at speeds comparable to that maintained by the subjects over the longest, 400-m distance [mean (SD) 1.20 (0.07) m x s(-1)]. PMID- 11192055 TI - Experimental muscle pain modulates muscle activity and work performance differently during high and low precision use of a computer mouse. AB - The aim was to investigate the influence of experimental muscle pain on performance and upper extremity muscle activity during occupational work requiring different levels of precision. Experimental muscle pain was induced by infusing hypertonic saline (0.3 ml, 5% NaCl) into the extensor carpi ulnaris (ECU) muscle. The same amount of isotonic saline was infused on a separate day to act as a control. Tasks requiring use of a computer mouse with high and low levels of precision were performed during the two sessions. Electromyographic (EMG) activity was measured from the ECU, the flexor carpi radialis (FCR) and the trapezius muscles. A group of 13 men participated in the study. Performance measured as work cycle time, cursor movements on the screen, and velocity of cursor movement were unaffected by muscle pain. The ECU muscle pain did not modulate EMG profiles of either the trapezius or FCR muscles either during high or during low precision work. During the low precision work the painful ECU muscle showed lower EMG activity in specific phases of the work cycle (highest activity phases) compared to the control session (P<0.05), whereas during the high precision work, experimental pain had no effect on the activity of the ECU muscle. In conclusion experimental muscle pain seems to modulate motor control differently depending on the precision level of the task. This may be of importance for our understanding of why some tasks lead to chronic musculoskeletal disorders. PMID- 11192056 TI - Energy cost and mechanical efficiency of riding a four-wheeled, human-powered, recumbent vehicle. AB - Oxygen consumption at steady state ( VO2, l x min(-1)) and mechanical power (W, W) were measured in five subjects riding a human-powered vehicle (HPV, the Karbyk, a four-wheeled recumbent cycle) on a flat concrete road at constant sub maximal speeds. The external mechanical work spent per unit of distance (W, J x m(-1)), as calculated from the ratio of W to the speed (v, m x s(-1)), was found to increase with the square of v: W = 8.12 + (0.262 x v2) (r = 0.986, n = 31), where the first term represents the mechanical energy wasted, over a unit of distance, against frictional forces (rolling resistance, Rr), and the second term (k x v2) is the work performed, per unit distance, to overcome the air drag. The rolling coefficient (Cr, obtained dividing Rr by m x g, where m is the overall mass and g is the acceleration of gravity) amounted to [mean (SD)] 0.0084 (0.0008), that is about 60% higher than that of a racing bicycle. The drag coefficient was calculated from the measured values of k, air density (p) and frontal area (A) [Cx = k x (0.5 x A x rho)-1], and amounted to 1.067 (0.029), that is about 20% higher than that of a racing bicycle. The energy cost of riding the HPV (Ck, J x m(-1)) was measured from the ratio of metabolic power above rest (net VO2, expressed in J x s(-1)) to the speed (v, m x s(-1)); the value of this parameter increased with the square of v, as described by: Ck = 61.45 + (0.675 x v(2)) (r = 0.711, n = 23). The net mechanical efficiency (eta) was calculated from the ratio of W to Ck: over the investigated speed range this turned out to be 0.22 (0.021). Best performance times (BPTs) of a "typical" elite athlete riding the Karbyk were calculated over the distances of 1, 5 and 10 km: these were about 8% longer than the BPTs calculated, on the same subjects, when riding a conventional racing bicycle. PMID- 11192057 TI - Effect of co-contractions on the cardiovascular response to submaximal static handgrip. AB - The aim of this study was to investigate the influence of concomitant involuntary contractions of different muscles on heart rate (HR) and blood pressure (BP) during a sustained, submaximal handgrip. Nine male subjects [23.6 (0.4) years, 177.0 (1.5) cm, and 73.0 (2.7) kg, means (SE)] participated in the experiment. The maximal integrated electromyographic activity (IEMG max) of four ipsilateral muscles, flexor digitorum (FD), biceps brachii (BB), rectus abdominalis (RA) and vastus lateralis (VA), was recorded. Then, after 30 min of rest, the subjects maintained a submaximal isometric handgrip for 2 min. Heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure and surface electromyography (EMG) of the four muscles were recorded. The amplitude and power spectrum of the EMG were analysed. During the handgrip the force was kept constant at 43 (1)% of the maximum voluntary contraction (MVC) only for 90 (12) s. After that time, the subjects were unable to maintain the target force which decreased continuously up to the end of the contraction (P<0.01) with a residual force of 27 (3)% MVC at t = 120 s. HR increased from 75 (3) beats x min(-1) at rest to 109 (6) beats x min( 1) at t = 120 s (P<0.01). SBP and DBP also increased from 112 (5) and 81 (2) mm Hg to 176 (5) and 133 (7) mm Hg, respectively (P<0.01). The EMG activity rose significantly for both FD and BB with a moderate increase for RA and VL. In fact, the individual contributions of FD and BB to the EMG activity of the four muscles were 52 (2)% and 37 (2)%, respectively, whereas the RA and VL contributed only 9 (1)% and 1.4 (0.1)%. The amplitude ratio of FD's EMG to the total EMG activity of the four muscles from which recordings were made decreased with time from 72% to 33% (P<0.01). The central command's level of activation, as reflected by the increased EMG activity of the four recorded muscles, was probably high enough to stimulate the cardiovascular centres through cortical spread (sometimes known as cortical irradiation). On the other hand, maintaining an isometric handgrip at 43% MVC reduced local muscle blood flow and metabolites known to stimulate type III and IV afferents then accumulated, which in turn induced a reflex-mediated elevation of blood pressure. However, the relative forces developed by the co contracting muscles were of low intensity (less than 20% MVC) and short duration compared to those of the muscle group under study. These results suggest that the mass of the muscle groups recruited during a fatiguing submaximal handgrip contributes little to the cardiovascular response. PMID- 11192058 TI - Physical activity and plasma interleukin-6 in humans--effect of intensity of exercise. AB - The present study included data from three marathon races to investigate the hypothesis that a relationship exists between running intensity and elevated concentrations of interleukin (IL)-6 in plasma. The study included a total of 53 subjects whose mean age was 30.6 [95% confidence interval (CI) 1.4] years, mean body mass 77.7 (95% CI 2.0) kg, mean maximal oxygen uptake (VO2max) 59.3 (95% CI 1.4) ml x min(-1) x kg(-1), and who had participated in the Copenhagen Marathons of 1996, 1997 or 1998, achieving a mean running time of 206 (95% CI 7) min. Running intensity was calculated as running speed divided by VO2 max. The concentration of IL-6 in plasma peaked immediately after the run. There was a negative correlation between peak IL-6 concentration and running time (r = -0.30, P<0.05) and a positive correlation between peak IL-6 concentration and running intensity (r = 0.32, P<0.05). The IL-1 receptor antagonist (IL-1ra) plasma concentration peaked 1.5 h after the run and there was a positive correlation between the peak plasma concentrations of IL-6 and IL-1ra (r = 0.39, P<0.01). Creatine kinase (CK) plasma concentration peaked on the 1st day after the run, but no association was found between peak concentrations of IL-6 and CK. In conclusion, the results confirmed the hypothesized association between plasma IL 6 concentration and running intensity, but did not confirm the previous finding of a connection between IL-6 plasma concentration and muscle damage. PMID- 11192059 TI - Ventilatory and circulatory responses at the onset of voluntary exercise and passive movement in children. AB - The purpose of this study was to investigate whether or not the ventilatory and circulatory responses at the onset of voluntary exercise and passive movement, especially at the initial stage (phase I), in children are the same as in adults. Ten pre-teenage male children and ten adult men participated in this study. Voluntary exercise and passive movement were performed in a sitting position for about 20 s. Both the exercise and the movement consisted of flexion-extensions of the lower leg from a vertical to horizontal position, either voluntarily or passively, with a frequency of about 60 x min(-1). Inspiratory minute ventilation (V1), tidal volume (VT), respiratory frequency, partial pressure of end-tidal CO2 and O2, heart rate (fc) and mean blood pressure (BP) before, during and after exercise or movement were measured using breath-by-breath and beat-to-beat techniques. Cardiorespiratory responses at the onset of voluntary exercise and passive movement were compared with the relative change (delta), which was estimated from the value at rest (100%). In the present study, it was found that: (1) the V1 during voluntary exercise were significantly lower in the children, mainly due to lower deltaVT; (2) the delta(f)c during voluntary exercise was almost the same in both groups, while deltaf(c) was significantly lower in the children during the last part of passive movement; (3) in the voluntary exercise and passive movement, the BP in the children was increased a little or remained close to the value at rest, while it was significantly decreased in the adults. As a result, there were significant differences in deltaBP between the two groups during voluntary exercise. These results suggest that the cardiorespiratory responses at the onset of voluntary exercise and passive movement may be modified during the growth process. PMID- 11192060 TI - Effect of postactivation potentiation on dynamic knee extension performance. AB - Six men and four women performed, in separate trials, maximal dynamic knee extensions with loads of 15%, 30%, 45% and 60% of maximal isometric knee extension peak torque (MVC). The dynamic extensions were done after postactivation potentiation (PAP) had been induced with a 10-s MVC, and in a control trial without PAP. PAP, measured as the increase in evoked twitch torque, was 53 (4)% (SE) and 43 (3)% at the time of the first and second extensions with each load. PAP failed to increase the attained peak velocity with any load; on the contrary, there was a trend for peak velocity to decrease in the first extension, which occurred approximately equal to 15 s after the 10-s MVC. The results suggest that fatigue produced by the 10-s MVC suppressed any benefit that could be derived from the induced PAP. A surface electromyogram (EMG) recorded from one muscle of quadriceps femoris gave no indication of activation failure in the first knee extension; however, activation impairment specific to the rate of force development cannot be ruled out. It is concluded that the strategy employed, namely of having knee extensions performed soon after the 10-s MVC to maximize PAP at the time of performance, was unsuccessful because there had been insufficient time for recovery from fatigue. It is possible that a longer recovery time, even at the cost of a diminished PAP, may have proved beneficial. PMID- 11192061 TI - Differential effect of knee extension isometric training on the different muscles of the quadriceps femoris in humans. AB - This study determined the effects of a short period of knee isometric training on the quadriceps muscles accessible to surface electromyography (EMG). For this purpose, a training (n = 9) and a control (n = 7) group were tested on five identical occasions at 1 week intervals during 4 weeks. The training group exercised three times a week by making isometric knee extensions at 80% of the maximal voluntary contraction (MVC). During the test sessions, maximal and submaximal torque and associated activations of the rectus femoris (RF), vastus lateralis (VL) and vastus medialis (VM) muscles were analysed. As a result of training, differences between MVC values of the two groups were highly significant (P<0.001), whereas only RF-EMG showed significant differences (P<0.05). The VL and VM did not present any significant changes in maximal activation. The EMG torque relationships were analysed individually before and after the training period. For the control subjects, EMG-torque relationships did not present significant changes while for the training group, these relationships showed a significant increase in RF, VL, and VM maximal activation in 6, 6 and 4 subjects, respectively, and a significant decrease in 1, 2 and 5 subjects, respectively. In almost all cases, a significant downward shift of the relationship was observed. This study confirmed that the parts of the quadriceps muscle tested present different adaptation capacities and demonstrate inter individual variability in the strategies used to enhance muscle strength. In conclusion, to analyse the neural effects resulting from training in a large and compartmentalized muscle like the quadriceps femoris, it is desirable to take into account each muscle independently. Moreover, we suggest that overall results obtained from the experiment population should be completed by an analysis on individuals. PMID- 11192062 TI - Cutaneous vasomotor adjustments during arm-cranking in individuals with paraplegia. AB - difference, P<0.05). The paraplegics developed a higher esophageal and leg skin temperature, which was attributed to the lack of active vasodilation and evaporative cooling over the legs. The results indicate that individuals with paraplegia suffer from impaired cutaneous vasoconstriction at the onset of arm exercise, and possess only a limited vasodilatory capability in the paralyzed regions. During intense exercise, thermoregulation depends critically on active cutaneous vasodilation and skin cooling. PMID- 11192063 TI - Estimation of %VO2 reserve from heart rate during arm exercise and running. AB - The purpose of the present investigation was to examine the relationship between the percent heart rate reserve (%HRR) in arm exercise and the corresponding percent oxygen uptake (VO2) reserve, and to compare this relationship to that occurring in running. Fourteen male physical education students took part in the study. Each subject performed a maximal running exercise test and a maximal arm cycling test. The subjects also performed three submaximal exercise bouts (in both exercise modes) at 30%, 60% and 80% of their HRR. The subjects were monitored for their heart rate (HR) at rest, maximal HR (HRmax), HR at submaximal work loads. maximal VO2 (VO2max), VO2 at rest and VO2 at submaximal loads. For each subject, load and exercise mode, %HRR and %VO2 reserve were calculated (from HRmax and VO2max as measured during running and arm cycling) and the relationship between the two was evaluated. The main finding of the present investigation is that the prediction of %VO2 reserve in arm cycling from %HRR is grossly overestimated when calculated from HRmax and VO2max measured during running. The prediction is better but still overestimated when calculated from HRmax and VO2max measured during arm cycling. The findings indicate a better prediction of %VO2 reserve from %HRR for running than for arm exercise. These findings should be taken into consideration when prescribing the target HR for arm training. PMID- 11192064 TI - The effect of motor learning in facioscapulohumeral muscular dystrophy patients. AB - Two models of motor learning (ML) practice (complex and simple) were used to investigate upper limb function in individuals with facioscapulohumeral dystrophy (FSHD). The effect of ML practice was studied by examining changes in the ability to undertake a simulated drinking task. In the complex model, seven FSHD patients and seven age- and gender-matched healthy volunteers were studied. Performance was assessed by measurement of the electromyographic (EMG) activity of the biceps brachii and brachioradialis, elbow joint flexion, shoulder joint flexion and abduction, maximum acceleration at the onset of movement, movement time and reaction time, both before and after a 30-min complex ML task. In the simple model, a second group of six FSHD patients and six age- and gender-matched healthy subjects were studied. The same parameters were measured as for the complex ML task, except that the EMG activity of the triceps and deltoid muscles (anterior part) were measured instead of that of the brachioradialis. In both studies, the FSHD patients showed significantly larger values for all parameters except the flexion of shoulder joint and reaction time, compared with controls before the ML task. In the FSHD group, while the complex ML resulted in decreases in the brachioradialis EMG activity (P<0.005) and reaction time (P<0.0001), the simple ML model resulted in significant changes towards the normal value in all parameters measured except shoulder flexion. The change in the measured variables towards normal values indicates that ML may help to improve performance in FSHD. PMID- 11192065 TI - In humans the oxygen uptake slow component is reduced by prior exercise of high as well as low intensity. AB - The aim of the study was to examine to what extent prior high- or low-intensity cycling, yielding the same amount of external work, influenced the oxygen uptake (VO2) slow component of subsequent high-intensity cycling. The 12 subjects cycled in two protocols consisting of an initial 3 min period of unloaded cycling followed by two periods of constant-load exercise separated by 3 min of rest and 3 min of unloaded cycling. In protocol 1 both periods of exercise consisted of 6 min cycling at a work rate corresponding to 90% peak oxygen uptake (VO2peak). Protocol 2 differed from protocol 1 in that the first period of exercise consisted of a mean of 12.1 (SD 0.8) min cycling at a work rate corresponding to 50% VO2peak. The difference between the 3rd min VO2 and the end VO2 (deltaVO2(6 3)) was used as an index of the VO2 slow component. Prior high-intensity exercise significantly reduced deltaVO2(6-3). The deltaVO2(6-3) was also reduced by prior low-intensity exercise despite an unchanged plasma lactate concentration at the start of the second period of exercise. The reduction was more pronounced after prior high- than after prior low-intensity exercise (59% and 28%, respectively). The results of this study show that prior exercise of high as well as low intensity reduces the VO2 slow component and indicate that a metabolic acidosis is not a necessary condition to elicit a reduction in deltaVO2(6-3). PMID- 11192066 TI - Cardiovascular responses to cold-water immersions of the forearm and face, and their relationship to apnoea. AB - Apnoea as well as cold stimulation of the face or the extremities elicits marked cardiovascular reflexes in humans. The purpose of this study was to investigate whether forearm immersion in cold water has any effect on the cardiovascular responses to face immersion and apnoea. We recorded cardiovascular responses to coldwater immersions of the forearm and face in 19 (part I) and 23 subjects (part II). The experimental protocol was divided in two parts, each part containing four tests: I1, forearm immersion during eupnoea; I2, face immersion during eupnoea; I3, forearm and face immersion during eupnoea; I4, face immersion during apnoea; II1, apnoea without immersion; II2, forearm immersion during apnoea; II3, face immersion during apnoea; and II4, forearm and face immersion during apnoea. The water temperature was 9-11 degrees C. Cold-water immersion of either the forearm or face was enough to elicit the most pronounced thermoregulatory vasoconstriction during both eupnoea and apnoea. During eupnoea, heart rate responses to forearm immersion (3% increase) and face immersion (9% decrease) were additive during concurrent stimulation (3% decrease). During apnoea, the heart rate responses were not affected by the forearm immersion. The oxygen conserving diving response seems to dominate over thermoregulatory responses in the threat of asphyxia. During breathing, however, the diving response serves no purpose and does not set thermoregulatory adjustments aside. PMID- 11192067 TI - Trunk muscle strength in eccentric and concentric lateral flexion. AB - The aim of this study was to investigate the position and velocity dependency of the strength (torque) output of lateral flexor muscles of the trunk. Twelve male volunteers with no history of back pain participated. Movement was constrained to the frontal plane and the velocity was controlled by an isokinetic dynamometer. The eccentric and concentric strength of lateral flexor muscles on the left side was measured in a supine position at velocities of 15, 30, 45 and 60 degrees x s( 1) and static strength at 20, 10, 0, -10 and -20 degrees of lateral trunk flexion. Average peak torque values ranged between 211 and 218 Nm (eccentric) and between 66 and 140 Nm (concentric) over all tested velocities, and the average static torque ranged between 80 and 172 Nm over all tested positions. The shape of the torque position curves was unaffected by speed and peak torque occurred at an average position of 11-15 degrees to the contralateral (right) side in both eccentric and concentric actions. In eccentric actions, torque output was significantly higher than that during concentric and static actions. Increasing the speed of contraction did not affect eccentric torque values, whereas both peak and angle-specific concentric torque decreased with increasing speed. These results are in general accordance with earlier findings from other muscle groups, such as the knee extensors. However, they are partially at variance with results obtained in studies of lateral lifting and lowering, indicating that there are other limiting factors in complex tasks that do not just involve the trunk muscles. PMID- 11192068 TI - Effect of dehydration on gastrointestinal function at rest and during exercise in humans. AB - Dehydration leads to the aggravation of gastrointestinal (GI) complaints during exercise. The aim of this study was to examine the effect of dehydration on various GI parameters during strenuous exercise. Ten healthy well-trained men were investigated in dehydrated and in euhydrated conditions. Dehydration took place before the experiments using a dehydration regimen in a sauna leading to a 3% loss of body mass. Each experiment consisted of 1 h pre-exercise rest, 1.5 h cycling at 70% maximal exercise intensity, and 3.5 h post-exercise rest. During cycling, liquid gastric emptying (GE), orocaecal transit time (OCTT) and intestinal permeability and glucose absorption were measured. The GI-symptoms were scored using a questionnaire. Body temperature, plasma volume and vasopressin were measured before and after cycling. The GE was significantly slower during dehydration [median time to peak 13C enrichment in the breath sample (13C-TTP) 23.6 min, range 13.7-50.0 min, P = 0.02] than in the control situation (median 13C-TTP 17.1 min, range 9.8-38.4 min). The OCTT was unchanged (median 173 min, range 98-263 min compared to median 128 min, range 98-195 min, P = 0.18). Dehydration did not change intestinal permeability, glucose absorption, plasma volume, rectal temperature or plasma vasopressin concentration. In the dehydration experiment, exercise induced a significant increase in nausea (P = 0.01) and epigastric cramps (P = 0.05), in contrast to the control situation. In both experiments, exercise led to a significant increase in rectal temperature and plasma vasopressin concentration, and a significant decrease in plasma volume. The increase in plasma vasopressin concentration was significantly higher in the dehydration experiment (P = 0.015). No significant differences in either the post-exercise rectal temperatures or in plasma volumes was observed. The difference in GE between the two experiments was significantly correlated with the difference in nausea score (r = 0.87, P = 0.002). We concluded that dehydration leads to a delayed GE but not to differences in OCTT, intestinal permeability or glucose uptake during intense cycling. The delay in GE is significantly associated with an increase in exercise-induced nausea. PMID- 11192069 TI - Vulvar intraepithelial neoplasia: historical aspects and current status. AB - Vulvar intraepithelial neoplasia (VIN) is the currently accepted generic designation for the spectrum of vulvar lesions with the histologic features of squamous dysplasia and squamous cell carcinoma in situ. Although several classifications of VIN have been espoused in the past 20 years, VIN can be readily classified into two principal clinicopathologic types: classic (bowenoid) VIN and simplex (differentiated) VIN. This manuscript summarizes the historical development and current status of our knowledge about VIN. Information on the clinical and pathologic aspects are detailed and illustrated, as are considerations of differential diagnosis. PMID- 11192070 TI - A half century in gynecological pathology: reminiscences of Robert E. Scully on his career. An interview with Robert H. Young. PMID- 11192071 TI - The pathology of intermediate trophoblastic tumors and tumor-like lesions. AB - An intermediate trophoblast is a distinctive trophoblastic cell population from which four trophoblastic lesions are thought to arise: exaggerated placental site (EPS), placental site nodule (PSN), placental site trophoblastic tumor (PSTT), and epithelioid trophoblastic tumor (ETT). EPSs and PSTTs are related to the differentiation of the intermediate trophoblast in the implantation site (implantation site intermediate trophoblast), whereas PSNs and ETTs are related to the intermediate trophoblast of the chorion laeve (chorionic-type intermediate trophoblast). EPSs and PSNs are nonneoplastic lesions, whereas PSTTs and ETTs are neoplasms with a potential for local invasion and metastasis. Microscopically, intermediate trophoblastic lesions can be confused with a variety of trophoblastic and nontrophoblastic tumors, but an appreciation of the morphologic features and immunophenotype allows their diagnosis to be relatively straightforward in most instances. Correct diagnosis is important because each of these lesions may require different therapeutic approaches. PMID- 11192072 TI - Familial ovarian cancer and early ovarian cancer: biologic, pathologic, and clinical features. AB - Women with ovarian cancer have poor overall survival rates, largely because the disease is so often diagnosed at an advanced, less curable stage. Because women with early ovarian cancer experience good survival rates, there is great interest in the study and detection of early disease. Familial ovarian cancer has been relevant to the study of early ovarian cancer in two different ways. First, women from ovarian cancer families often undergo prophylactic oophorectomy to prevent development of this disease. These ovaries have been studied for pathologic or molecular features that might represent early preinvasive disease. Second, screening tests to detect presymptomatic ovarian cancer have selectively targeted this population because of the increased positive predictive value of these tests in this population. A review of the clinical, pathologic, epidemiologic, and molecular biologic aspects of familial ovarian cancer provides a background to facilitate understanding these issues. PMID- 11192073 TI - Immunohistochemical analysis of gynecologic tumors. AB - Ancillary techniques such as immunohistochemistry (IHC) enable the surgical pathologist to extract additional information from fixed, deparaffinized tissue specimens and to provide data critical to optimal clinical management of the patient. In this review of applications of IHC to the analysis of gynecologic malignancies, the usefulness of immunohistochemical analysis of neoplasms of the cervix, endometrium, and ovary is summarized. In the uterine cervix, dysplasia is associated with qualitative and quantitative alterations in the expression of the Ki-67 antigen expression, as well as an ability to detect human papillomavirus. Endometrial endometrioid adenocarcinomas display a highly characteristic immunophenotype, with coexpression of cytokeratin and vimentin and demonstration of foci of high molecular weight cytokeratin expression; in addition, IHC analysis of estrogen and progesterone receptor and p53 expression can provide important prognostic information about this tumor. Stromal tumors of the endometrium may display a partial smooth muscle immunophenotype, but novel markers such as CD10 provide new tools for the identification of these tumors. The immunophenotypes of the normal ovarian surface epithelium (OSE) and corresponding tumors display significant overlap with, but important distinctions from, mesothelium, and important new markers such as the Wilms tumor gene product can prove useful in the identification of carcinomas of the OSE. Important prognostic markers for carcinomas of the OSE include the HER-2/neu gene product and p53, alterations of which can both be assessed by IHC techniques. Finally, the recent availability of markers of ovarian stroma, including Melan-A and inhibin-alpha, has provided a means for the positive identification of ovarian stromal tumors, which can manifest protean histological appearances. PMID- 11192074 TI - Value of inhibin staining in gynecological pathology. AB - Recent years have seen the publication of many articles investigating the value of antibodies against inhibin in diagnostic surgical pathology. This review concentrates on the uses of inhibin staining in gynecological pathology. alpha inhibin is diagnostically the most useful antibody and is a sensitive immunohistochemical marker of most ovarian sex cord-stromal tumors and, as such, is of value in the diagnosis of this heterogeneous group of neoplasms that can be confused morphologically with a wide range of other tumors. Because the antibody is not entirely specific for ovarian sex cord-stromal tumors, it should always be used as part of a larger panel. alpha-inhibin staining may also be of value in confirming late recurrence or metastasis of an ovarian sex cord-stromal tumor, especially a granulosa cell tumor. Sex cord-like elements within uterine tumors resembling ovarian sex cord tumors are also commonly immunoreactive with alpha inhibin, perhaps indicating true sex cord differentiation. alpha-inhibin staining may also be of value in cytological preparations in confirming a functional cyst and excluding a cyst or cystadenoma of epithelial origin. Syncytiotrophoblastic cells are also immunoreactive, as are most trophoblastic tumors. Thus, positive staining may be of value in confirming an intrauterine gestation or in the diagnosis of a trophoblastic neoplasm. Another gynecological neoplasm that is commonly positive with alpha-inhibin is the so-called female adnexal tumor of probable wolffian origin, and, therefore, the antibody is of no value in the distinction of this neoplasm from a sex cord-stromal tumor, tumors that are often in the differential diagnosis. PMID- 11192075 TI - History of gynecological pathology. IX. Dr. John Albertson Sampson. 1921. PMID- 11192076 TI - The "resin-capture-release" hybrid technique: a merger between solid- and solution-phase synthesis. AB - A polymer-assisted organic synthesis that combines the concept of solid-phase synthesis with the idea of polymer-supported scavenging reagents has recently appeared on the chemistry scene. This technique has frequently been termed the "resin-capture-release" methodology and is initiated by the immobilization of a small molecule on a polymeric support. This intermediate is subjected to a second transformation by adding a new reaction partner in solution. This reactant plays two roles: a) the chemical alteration of the polymer-bound intermediate and b) the simultaneous release of this reaction product from the resin back into solution. This new concept is presented and future prospects are discussed. PMID- 11192077 TI - Entropy-driven hydrogen bonding: stereodynamics of a protonated, N,N-chiral "proton sponge". AB - The C2-symmetric ("[DL]") and achiral ("[meso]") diastereoisomers of the hydrogen iodide salt of 1,8-bis-(N-benzyl-N-methylamino)naphthalene ([2H]-[I] ) interconvert in solution. Direct interconversion of the diastereoisomers of [2H]+ must involve hydrogen bond fission (to give "[nonHB-2H+]") and rotation-inversion of the non-protonated nitrogen centre. The global activation parameters (deltaH++ and deltaS++) for diastereoisomer interconversion in [D7]DMF have been determined from rate data obtained by temperature-drop and magnetisation-transfer 13C NMR spectroscopy over a temperature range of 170 degrees C. The process is found to have a high entropy of activation in both directions (deltaS++=163(+/-4) and 169(+/-4) JK(-1)mol(-1)) and this is suggested to arise through hydrogen bonding of the ammonium centre in [nonHB-2H+] with the solvent ([D7]DMF). Comparison of the enthalpy of activation (deltaH++) with that earlier found for diastereoisomer interconversion of the free-base form 2 suggests that the intramolecular hydrogen bond in [2H]+ is roughly equal in enthalpic strength (deltaH) with that made with the solvent ([D7]DMF) in the non-hydrogen-bonded intermediate [nonHB-2H+]. As such, the hydrogen bonding in [2H]+ may be considered as predominantly an entropically driven process, without any unusual enthalpic strength. PMID- 11192078 TI - Carbenerhodium complexes of the half-sandwich-type: synthesis, substitution, and addition reactions. AB - A series of carbenerhodium(I) complexes of the general composition [(eta5 C5H5)Rh(=CRR')(L)] (2a-2i) with R = R'= aryl and L = SbiPr3 or PR3 has been prepared from the square-planar precursors trans-[RhCl(=CRR')(L)2] and NaC5H5 in excellent yields. Reaction of the triisopropylsibane derivative 2a. which contains a rather labile Rh-Sb bond, with CO, PMe3, and CNR (R = Me, CH2Ph, tBu) leads to the displacement of the SbiPr3 ligand and affords the substitution products [(eta5-C5H5)Rh(=CPh2)(L)] (3-7). In contrast, treatment of the triisopropylphosphane compound 2c with CO and CNtBu leads to the cleavage of the Rh=CPh2 bond and gives besides [(eta5-C5H5)Rh(PiPr3)(L)] (10, 12) by metal assisted C-C coupling diphenylketene Ph2C=C=O (11) or the corresponding imine Ph2C=C=NtBu (13). While the reaction of 2a, c with C2H4 yields [(eta5 C5H5)Rh(C2H4)(L)] (14, 15) and the trisubstituted olefin Ph2C=CHCH3 (16), treatment of 2a, c with RN3 leads to the cleavage of both the Rh-EiPr3 and Rh=CPh2 bonds and gives the chelate complexes [(eta5-C5H5)Rh(kappa2-RNNNNR)] (19, 20). The substitution products 3 (L=CO) and 4 (L= PMe3) react with an equimolar amount of sulfur or selenium by addition of the chalcogen to the Rh=CPh2 bond to generate the complexes [(eta5-C5H5)Rh(kappa2-ECPh2)(L)] (21-24) with thio- or selenobenzophenone as ligand. Similarly, treatment of 3 with CuCl affords the unusual 1:2 adduct [(eta5-C5H5)(CO)Rh(mu-CPh2)(CuCl)2] (25), which reacts with NaC5H5 to form [(eta5-C5H5)(CO)Rh(muCPh2)Cu(eta5-C5H5)] (26). The molecular structures of 3 and 22 have been determined by X-ray crystallography. PMID- 11192079 TI - The bridging function of an apparently nonbridging ligand: dinuclear rhodium complexes with Rh(mu-SbR3)Rh as a molecular unit. AB - Novel dinuclear rhodium complexes of the general composition [Rh2Cl2(mu-CRR')2(mu SbiPr3)] (4-6) were prepared by thermolysis of the mononuclear precursors trans [RhCl(=CRR')(SbiPr3)2] in excellent yield. The X-ray crystal structure analysis of 4 (R = R' = Ph) confirms the symmetrical bridging position of the stibane ligand. Related compounds [Rh2Cl2(mu-CPh2)(mu-CRR')(mu-SbiPr3)] (7, 8) with two different carbene units were obtained either from trans-[RhCl(=CPh2)(SbiPr3)2] (1) and RR'CN2 or by a conproportionation of 4 and 5 (R = R' = p-Tol) or 4 and 6 (R= Ph, R' = p-Tol), respectively. While CO reacts with 4 to give the polymeric product [[RhCl(CPh2)(CO)]n] (9), tert-butyl isocyanide replaces the bridging stibane and yields [Rh2Cl2(mu-CPh2)2(mu-CNtBu)] (10). The reaction of 4 with tertiary phosphanes PR3 leads to complete bridge cleavage and affords the mononuclear compounds trans-[RhCl(=CPh2)(PR3)2] (11-15). In contrast, treatment of 4 with SbMe3 and SbEt3 yields the related triply bridged complexes [Rh2Cl2(mu CPh2)2(mu-SbR3)] (16, 17) by substitution of SbiPr3 for the smaller stibanes. The displacement of the chloro ligands in 4-6 and 10 by n5-cyclopentadienyl gives the dinuclear complexes [(n5-C5H5)2Rh2(mu-CRR')2] (18-20) and [(n5-C5H5)2Rh2(mu CPh2)2(mu-CNtBu)] (21), of which 18 (R = R' = Ph) was characterized crystallographically. PMID- 11192080 TI - Vibrational circular dichroism and absolute configuration of chiral sulfoxides: tert-butyl methyl sulfoxide. AB - Mid-infrared vibrational unpolarised absorption and vibrational circular dichroism (VCD) spectra of CCl4 solutions of tert-butyl methyl sulfoxide (1) are reported. The spectra are compared to ab initio density functional theory (DFT) calculations carried out using two functionals, B3PW91 and B3LYP, and two basis sets, 6-31G* and TZ2P. The VCD spectra are calculated using Gauge-invariant atomic orbitals (GIAOs). The analysis of the VCD spectrum confirms the R(-)/S(+) absolute configuration of 1. The advantages and disadvantages of VCD spectroscopy in determining the absolute configurations of chiral sulfoxides are discussed. PMID- 11192081 TI - Discrimination of A/T sequences in the minor groove of DNA within a cyclic polyamide motif. AB - Eight-ring cyclic polyamides containing pyrrole (Py), imidazole (Im), and hydroxypyrrole (Hp) aromatic amino acids recognize predetermined six base pair sites in the minor groove of DNA. Two four-ring polyamide subunits linked by (R) 2,4-diaminobutyric acid [(R)H2Ngamma] residue form hairpin polyamide structures with enhanced DNA binding properties. In hairpin polyamides, substitution of Hp/Py for Py/Py pairs enhances selectivity for T. A base pairs but compromises binding affinity for specific sequences. In an effort to enhance the binding properties of polyamides containing Hp/Py pairings, four eight ring cyclic polyamides were synthesized and analyzed on a DNA restriction fragment containing three 6-bp sites 5'-tAGNNCTt-3', where NN = AA, TA, or AT. Quantitative footprint titration experiments demonstrate that contiguous placement of Hp/Py pairs in cyclo-(gamma-ImPyPyPy-(R)H2Ngamma-ImHpHpPy-) (1) provides a 20-fold increase in affinity for the 5'-tAGAACTt-3' site (Ka = 7.5 x 10(7)M(-1)) relative to ImPyPyPy (R)H2Ngamma-ImHpHpPy-C3-OH (2). A cyclic polyamide of sequence composition cyclo (gamma-ImHpPyPy-(R)H2Ngamma-ImHpPyPy-) (3) binds a 5'-tAGTACTt-3' site with an equilibrium association constant KA= 3.2 x 10(9)M(-1), representing a fivefold increase relative to the hairpin analogue ImHpPyPy-(R)H2Ngamma-ImHpPyPy-C3-OH (4). Arrangement of Hp/Py pairs in a 3'-stagger regulates specificity of cyclo (gamma-ImPyHpPy-(R)H2Ngamma-ImPyHpPy-) (5) for the 5'-tAGATCTt-3' site (Ka = 7.5 x 10(7)M(-1)) threefold increase in affinity relative to the hairpin analogue ImPyHpPy-(R)H2Ngamma-ImPyHpPy-C3-OH (6), respectively. This study identifies cyclic polyamides as a viable motif for restoring recognition properties of polyamides containing Hp/Py pairs. PMID- 11192082 TI - The first water-soluble 3(10)-helical peptides. AB - Two water-soluble 3(10)-helical peptides are synthesized and fully characterized for the first time. The sequence of these terminally blocked heptamers comprises two residues of the Calpha-trisubstituted alpha-amino acid 2-amino-3-[1-(1,4,7 triazacyclononyl)]propanoic acid and five residues of a Calpha-tetrasubstituted alpha-amino acid (either alpha-aminoisobutyric acid or isovaline). Using CD and NMR techniques we were able to show that both heptapeptides are well structured in water, and that the type of conformation adopted is indeed the ternary 3(10) helix. PMID- 11192083 TI - [Cp2V] migration along an octatetrayne chain: from the monometallic complex (Cp2V(2-4eta-tBuC triple bond C2-C triple bond CC triple bond CtBu)] to the dimetallic complex. AB - The oxidative addition of one equivalent of [Cp2V] (4) to the tetrayne ligand tBuC triple bond CC triple bond CC triple bond CC triple bond CtBu (5) gives the monometallic complex [Cp2V(3-4eta-tBuC triple bond C-C2-C triple bond CC triple bond CtBu)] (7). Compound 7 reacts further with a second equivalent of [Cp2V] to give the dimetallic complex [(Cp2V)2(1-2eta:7-8eta-tBuC2-C triple bond CC triple bond C-C2tBu)] (8), which involves a shift of the first coordinated [Cp2V] unit from the internal C3-C4 to the external C1-C2 positions on the alkynyl ligand. Compound 8 is also directly obtained by the addition of two equivalents of [Cp2V] to 5. Reversibly, reaction of 8 with 5 leads to 7. This exchange reaction between 7 and 8 by adding successively 5 and 4 has been monitored by EPR spectroscopy. By contrast, the oxidative addition of one or two equivalents of [Cp2V] to the tetrayne ligand PhC triple bond CC triple bond CC triple bond CC triple bond CPh (6) gives the homodimetallic complex [(Cp2V)2(1-2eta:7-8eta-PhC2-CC triple bond CC triple bond C-C2-Ph)] (9). Both monometallic and dimetallic complexes 7, 8, and 9 have been characterized by X-ray diffraction. Magnetic moment measurements for 8 and 9 from 300 to 4 K indicated a weak antiferromagnetic J exchange coupling of -12.5 and -4.1 cm(-1), respectively. PMID- 11192084 TI - Self-assembly and structure of interconverting multinuclear inorganic arrays: a. AB - Coordination of the pentatopic ligand 3 with AgI leads to the simultaneous self assembly of two polynuclear architectures: a [4 x 5] grid-type species 10 and a quadruple-helicate 11, which contain twenty and ten silver ions. respectively. Their structures have been established by X-ray diffraction analysis of the crystals obtained as a mixture on crystallisation. Complex 10 contains two [2 x 5]-AgI10 rectangular subgrids located on opposite sides of an array of parallel ligands of 3 that are twisted into a transoid N=C-C=N arrangement around the central C-C bond; it may thus be formulated as a grid of grids: [2 x (2 x 5)]. Complex 11 is an inorganic quadruple helicate that consists of two sets of two parallel ligands of 3 connected by an array of ten silver ions. Both compounds 10 and 11 are novel types of polynuclear complexes that are composed of two subunits. Their formation points to the possibility of generating specific arrays of metal ions by self-assembly, involving, in particular, a combination of subunits within the overall entity. They represent organised patterns of ion dots of special significance in view of their formal relationship to quantum dots. PMID- 11192085 TI - The binding ability of iron bonded to porphodimethene: structural, magnetic, and electronic relationship to iron porphyrin complexes. AB - The availability of the parent compound, meso-hexaethylporphodimetheneiron(II), [(Et6N4)Fe] (2), of this report results from a novel synthetic methodology that makes [Et6N4Li2] (1) easily available. The major focus is on how the axial positions, which are the key reactive sites in metalloporphyrins, and the electronic configuration of the metal can be affected by the breakdown of the aromaticity of the porphyrin skeleton and by the nonplanar conformation of the ligand. DFT calculations indicate a 3B1(dz2)1(dyz)1 ground state for 2 versus the 3A2(dxz)1(dyz)1 ground state in the porphyrin analogue. The intermediate-spin state (S = 1) of 2 changed drastically upon addition of one or two axial ligands, as hexacoordination is preferred by iron(II). The hexacoordinate complexes [(Et6N4)Fe(L)(L')] (L = L' = THF, 3; L = L' = Py, 4; L = PhNO, L' = Py, 14) have been isolated and structurally characterized. Strong-field ligands lead to a low spin diamagnetic state for iron(II), namely for complexes 4-7, 9, and 14, whereas 3 is a typical d6 high-spin complex, as is the pentacoordinate [(Et6N4)Fe(CN)]Bu4N (8). The structural analysis showed common features for 6, 7, 9, and 14: i) a small displacement of the metal from the N4 plane, and ii) an N4 cavity, larger than that in the corresponding porphyrins, affecting the Fe-N bond lengths. The 1H NMR spectrum is quite diagnostic of the two-fold symmetry in the diamagnetic hexacoordinate complexes, revealing either a D2h or a C2v symmetry. The CO stretching frequency (1951 cm(-1)) in complex 6 probes the good electron density at the metal. The one-electron oxidation of 2 led to pentacoordinate iron(III) derivatives [(Et6N4)Fe(Cl)] (10), [(Et6N4)2Fe2(mu-O)] (11), and [(Et6N4)2Fe2(mu-p-OC6H4-O)] (12). Complex 10 is a typical high-spin iron(III) (5.85muB at 298 K), while 11 and 12 behave as antiferromagnetic coupled iron(III) (J = -9.4cm(-1), 12, and J = -115cm(-1), 11). In complexes 10, 11, and 12 iron is sitting in a quite distorted square pyramidal geometry, in which the ligand displays a very distorted roof conformation with different degrees of ruffling. Distinctive structural and magnetic features have been found for the nitrosyl derivative [(Et6N4)Fe-NO], which has a low-spin state (S = 1/2) and the following structural parameters: Fe-N-O, 147.3(2) degrees; Fe-N, 1.708(2) A; N-O, 1.172(3) A. A comparative structural, magnetic, and theoretical analysis of the compounds listed above has been made with the analogous porphyrin derivatives. The detailed structural investigation has been mapped through the X-ray analysis of 2, 7, 8, 9, 11, 13, and 14. PMID- 11192086 TI - Quantitative evaluation of Lewis acidity of metal ions derived from the g values of ESR spectra of superoxide: metal ion complexes in relation to the promoting effects in electron transfer reactions. AB - The g values of ESR spectra of superoxide-metal ion complexes (O2(*-)-Mn+, n = 1, 2, 3) are determined in acetonitrile at 143 K. The binding energies (deltaE) of metal ions with O2*- have been evaluated from deviation of the gzz values from the free spin value. The deltaE values are well correlated with the catalytic reactivities of metal ions in electron transfer from cobalt(II) tetraphenylporphyrin to O2 and p-benzoquinone, which does not occur in the absence of metal ions under otherwise the same experimental conditions. The deltaE values can thereby be used as the first quantitative measure for Lewis acidity of metal ions in relation with the catalytic reactivities in electron transfer reactions. PMID- 11192087 TI - Interanionic (-)O-H...O(-) interactions: a solid-state and computational study of the ring and chain motifs. AB - The (-)O-H...O(-) interaction formed by the anions HCO3-, HCO4, HC4O4 and HC5O5- (HA-), obtained upon monodeprotonation of the corresponding carbonic, oxalic, squaric and croconic acids (H2A), has been investigated theoretically and experimentally. The ring (RING) and chain (CHAIN) hydrogen bond motifs established between these anions have been analysed in terms of geometry and energy and their occurrence in crystalline salts investigated by searching the Cambridge Structural Database (CSD) and the Inorganic Chemistry Structural Database (ICSD). It has been shown that hydrogen carbonates form RINGs, with the notable exception of NaHCO3, while only CHAINs are known for hydrogen oxalates. Hydrogen squarates and hydrogen croconates can form both RINGs and CHAINs. The structures of Rb- and Cs- hydrogen croconates, which present the two alternative motifs, have been discussed together with that of the hydrated salt NaHC5O5.H2O. The relationship between RING and CHAIN has been examined in the light of ab initio calculations. A rigorous quantum chemical study of the nature of the interanionic (-)O-H...O(-) interaction in both vacuum and condensed phase has shown that the interaction energy is dominated by the electrostatic component which becomes attractive at short O...O distances (less than 2.5 A) if the net ionic charge on the anion is delocalised away from the -OH group. It has been demonstrated that the RING motif is slightly metastable with respect to dissociation in the gas phase, but becomes stable in the crystal owing to the influence of the Madelung field. However, the CHAIN motif is unstable both in the gas phase and in the crystal. It is argued that interanionic (-)O-H...O(-) interactions ought to be regarded as stabilising bonding interactions rather than proper intermolecular hydrogen bonds because the RING and CHAIN aggregates are not energetically stable on an absolute scale of bonding energy (i.e., in the absence of counterions). The presence of very short non-hydrogen-bridged O...O contacts resulting from charge compression of polyatomic anions bridged by alkali cations is also discussed. PMID- 11192088 TI - Sol-gel polycondensation in a cyclohexane-based organogel system in helical silica: creation of both right- and left-handed silica structures by helical organogel fibers. AB - Chiral amide- and urea-type organic gelators (1-6), based on cyclohexanediamine, have been prepared, and the superstructures of the organogels were evaluated by circular dichroism (CD), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The CD spectrum of the amide-based organogel system 1+2 exhibited a negative sign for the first Cotton effect, indicating that the dipole moments in the gelator aggregate orient into an anticlockwise direction. In contrast, the system 3+4 has a positive sign for the first Cotton effect, indicating that they orient into a clockwise direction. In the mixture of urea- and amide-based organogels, CD spectra of 5+2 and 6+4 revealed negative and positive signs, respectively. The helical structure of the amide-based organogels 1+2 and 3+4 clearly showed left- and right-handed structures, respectively, by SEM. To transcribe the chiral, helical structures of the organogels into silica gel, the sol-gel polycondensation of tetraethoxysilane (TEOS) was carried out in acetonitrile or ethanol. Very surprisingly, the left- and right-handed structures of the silica can be created by transcription of left- and right-handed structures of the organogels 1+2 (R enantiomer) and 3+4 (S enantiomer), respectively. In addition, in the mixture systems of urea- and amide-based organogels, the right- and left-handed structures of the organogels 5+2 (R enantiomer) and 6+4 (S enantiomer) were precisely transcribed into the silica structure. The findings suggest that the sol-gel polycondensation proceeds along the surface of the helical structure of the organogels. We therefore believe that the sol-gel polycondensation by means of molecular assembly templates abundantly built in the organogel phase is a new strategy to create superstructured silica materials. PMID- 11192089 TI - Imidovanadium(v) complexes as reaction partners for kinetically stabilized phosphaalkynes: synthesis of 1,2,4-azaphosphavanada(v)-cyclobutenes, 1,3,5 triphosphabenzenes, and 1H-1,2,4-azadiphospholes. AB - Cycloaddition reactions of the kinetically stabilized phosphaalkynes 1 with the imidovanadium(v) trihalides 9 furnish the 1,2,4-azaphosphavanada(v)cyclobutenes 10. The stability of these novel metallacyclic compounds depends solely on the substitutents of the imido unit. Thus, the imidovanadium(v) species 9 with tertiary alkyl groups on the N atom form stable addition products with 1 while in the cases of compounds 9 with a lower degree of substitution at N (primary and secondary alkyl groups) the primarily formed adducts 10 undergo irreversible decomposition to afford the 1H-1,2,4-azadiphospholes 13. Reactions of an excess of the phosphaaalkyne 1 with the vanadium complexes 9 furnish the corresponding triphosphabenzenes 8 in good yields (36-68%). A catalytic reaction course has been demonstrated for the all-tert-butyl system 1a/9a in which the metallacyclic species 10a serves as the catalytically active species. Poisoning of the catalyst leads to a second reaction pathway, which results in formation of the azatetraphosphaquadricyclanes 16. By means of the stepwise use of different phosphaalkynes 1a,b this methodology provides the first access to the differently substituted triphosphabenzenes through cyclotrimerization. PMID- 11192090 TI - 4-Oxo-2,3,5,6-tetrafluorocyclohexa-2,5-dienylidene--a highly electrophilic triplet carbene. AB - The 4-oxocyclohexa-2,5-dienylidenes are an interesting class of highly electrophilic carbenes. We investigated the reactivity of the 2,3,5,6 tetrafluorinated and -tetrachlorinated derivatives 1b and 1c with small molecules under conditions of matrix isolation. The reactions with molecular oxygen and with carbon monoxide produce the expected carbonyl O-oxides and ketenes, respectively. As a result of the extreme electrophilicity of 1b and c both carbenes insert with no or very small activation barriers into H2 or the CH bonds of hydrocarbons. Obviously, spin restrictions for these formally spin-forbidden reactions do not result in substantial thermal activation barriers. PMID- 11192091 TI - Spontaneous symmetry breaking in the formation of a dinuclear gadolinium semiquinonato complex: synthesis, high-field EPR studies, and magnetic properties. AB - The synthesis and characterisation of an asymmetric dinuclear gadolinium(III) semiquinonato complex, namely [Gd2(HBPz3)2(dtbsq)4] CHCl3 (1; HBPz3 = hydrotris(pyrazolyl)borate, dtbsq = 3,5-di-tert-butyl-O-semiquinone), is reported. The crystal structure of 1 was determined at room temperature. It crystallises in the triclinic system P1, with a = 16.735(5) A, b = 17.705(5) A, c = 19.553(5) A, alpha = 99.680(5) degrees, beta = 109.960(5), gamma = 107.350(5) degrees, Z = 2 and R = 9.96. The structure of 1 consists of a dinuclear asymmetric unit in which the two gadolinium(III) ions have coordination numbers of eight and nine. Three of the dioxolene molecules act as asymmetric bridging ligands, while the fourth molecule behaves as a bidentate ligand towards a single metal ion. The magnetic properties of 1 were investigated by means of susceptibility measurements and high-field electron paramagnetic resonance (HF EPR) spectroscopy. They revealed an S = 0 ground spin state with excited states of higher spin very close in energy and a small negative zero-field splitting with a transverse anisotropy term for a S = 7 state. PMID- 11192092 TI - The Chatt-Dewar-Duncanson model revisited: X-ray, DFT and NMR studies of rhodium alkene binding--deviations from structural ideality. AB - An analysis has been made of deviations from ideal centrosymmetric bonding of alkenes to transition metals in square-planar complexes. Three separate approaches have been employed. Firstly, the geometries obtained for a series of X ray crystal structures of monosubstituted rhodium-alkene complexes have been obtained. Secondly, DFT computations on closely related rhodium-alkene complexes are reported. Thirdly. the data have been augmented by recourse to the crystal structure serach and retrieval file (CSSR) database to retrieve the X-ray data for square-planar ethene and monosubstituted alkene complexes. The results obtained from these analyses provide a consistent picture. Two distortions from ideality are important: twisting of the alkene about the axis between the metal (M) and the alkene centroid and rolling of the alkene around a cylinder enclosing the metal, such that the two C-M bonds remain equal in length. The presence of both of these is verified through both X-ray structure determinations and DFT calculations. For the rolling distortion, there is a relationship between the electronic character of the substituent on the alkene and the direction of roll. The net effect of this is to place the more nucleophilic carbon of the alkene closer to the square plane. The significance of this for the regiochemistry of the Heck reaction is briefly discussed. PMID- 11192093 TI - Ladderlike oligomers; intramolecular hydrogen bonding, push-pull character, and electron affinity. AB - Symmetrical 2,5-bis(2-aminophenyl)pyrazines have been synthesized by application of the Stille coupling strategy. These cotrimers feature three important properties, namely strong intramolecular hydrogen bonding, push-pull character, and high electron affinity. The presence of intramolecular hydrogen bonds has been confirmed by 1H NMR, IR spectroscopy, and single-crystal X-ray diffraction. The hydrogen bond strength can be increased by substituting the amino groups with stronger electron-withdrawing functionalities. Despite the anticipated enhanced pi-conjugation through planarization, a hypsochromic shift was observed in the UV/Vis spectra, explained by a decrease in push-pull character. The electron affinity of the cotrimers was deduced from the first reduction potentials measured by cyclic voltammetry and is related to the electron-withdrawing character of the amino substituents. The results obtained have been compared with those of the corresponding 4-aminophenyl analogues and show that intramolecular hydrogen bonds can be used to design polymers with enhanced pi conjugation as well as a high electron affinity. PMID- 11192094 TI - Biomimetic catalysis with immobilised organometallic ruthenium complexes: substrate- and regioselective transfer hydrogenation of ketones. AB - Chloro-(eta6-arene) complexes of ruthenium(II) with N-sulfonyl-1,2 ethylenediamine ligands that have one or two styrene side chains have been synthesised and characterised. The chloro ligand was substituted with a diphenylphosphinato ligand and the resulting organometallic complexes are transition state analogues for the ruthenium-catalysed transfer hydrogenation of benzophenone. Following the protocol of molecular imprinting, these complexes were copolymerised with ethylene glycol dimethacrylate (EGDMA) in the presence of a porogen. The polymers were ground and sieved, and the phosphinato ligand was substituted with a chloro ligand, thus generating a shape-selective cavity in close proximity to the catalytically active metal centre. When tested for their ability to catalyse the reduction of benzophenone, the imprinted polymers showed a significantly higher activity (up to a factor of seven) than control polymers without cavities. Out of a mixture of seven different aromatic and aliphatic ketones, benzophenone was preferentially reduced when the imprinted polymer was used. Furthermore, the specificity of the catalyst for diaryl ketones has been confirmed in a reaction with a bifunctional substrate, 4-acetyl-benzophenone; the diaryl ketone was reduced faster with the imprinted catalyst than the acetyl group. The opposite regioselectivity was observed with the control polymer. Both the activity and the selectivity of the imprinted catalysts are dependent on how the ruthenium complexes are attached to the polymer backbone. A double connection proved to give superior results. PMID- 11192095 TI - Trimethylsilyl- and trimethylstannyldimethylphosphane--convenient and versatile reagents for the synthesis of polyfluoroaryldimethylphosphanes. AB - Trimethylsilyldimethylphosphane (Me3SiPMe2) and the corresponding tin compound (Me3SnPMe2) were used as reagents for the substitution of fluorine by the Me2P group in polyfluoroarenes C6F5X (X = F, H, Cl, CF3) and C5NF5. The reactions occur even under mild conditions (T = 0-20 C), either in benzene or without solvent, to give as a rule 4-X-1-(dimethylphosphano)tetrafluorobenzenes (XC6F4PMe2, 1-4) and 4-(dimethylphosphano)tetrafluoropyridine (C5NF4PMe2, 5), respectively, in yields between 75 and 95%. In the case of C6F6, double substitution is also observed, which affords 1,4 bis(dimethylphosphano)tetrafluorobenzene (6). A very efficient route to the compounds XC6F4PMe2 (X = F, H, Cl, CF3) and C5NF4PMe2 was developed as a one-pot reaction of the corresponding fluoroarenes with tetramethyldiphosphane (P2Me4) and trimethyltin hydride (Me3SnH) at moderate temperatures. This process was tested for C6F6 and perfluorobiphenyl which gave C6F5PMe2 (1) and 4,4' bis(dimethylphosphano)octafluorobiphenyl (7), respectively. The results, which included kinetic measurements that used the intensities of the 31P signals, revealed the influence of the substrate type on the rate of reaction in the sequence: C5NF5>C6F5CF3> C6F5Cl, C6F5PMe2>C6F5H>C6F6>> C6H5F. Ab initio calculations were carried out on the model reactions of pentafluoropyridine with silylphosphane, phosphane or phosphide to discriminate between possible reaction mechanisms. The novel phosphanes were characterised by spectroscopic investigations (NMR, MS), by preparation of the related thiophosphanes ArFP(=S)Me2 (8-14), their spectroscopic and analytic data and single crystal X ray diffraction studies on five of these derivatives. PMID- 11192096 TI - Coordination polymerization in water affording amorphous polyethylenes. AB - The coordination polymerization of ethylene in water as a reaction medium was studied. Rubbery amorphous branched polyethylene was obtained when a known cationic diimine-substituted methyl complex was employed as a catalyst precursor. High rates of up to 900 TOh(-1) (turnover frequency) were observed. In contrast to solution polymerization in an organic solvent, the rate of suspension polymerization in water increases greatly with ethylene pressure in the range up to 20 bar; this indicates control of the polymerization rate by the concentration of the olefin monomer at the catalytically active site. The effect and mode of mass transfer phenomena were studied. A high catalyst stability in the aqueous coordination polymerization was observed. It was found to be due to an "encapsulation" of the water-insoluble catalyst precursor in the hydrophobic amorphous polymer during the polymerization reaction, and this resulted in strongly restricted accessibility for the aqueous phase. Surprisingly, exposure of the water-stable catalyst precursor to ethylene monomer in solution in the presence of water resulted in immediate decomposition. Polymer microstructure, and thermal and mechanical properties were investigated. The different degree of branching, molecular weight, and corresponding macroscopic properties of the polymers obtained in water as a reaction medium versus solution polymerization in methylene chloride under the same conditions are due to the different phase behavior during polymerization (suspension vs. solution), as opposed to an effect of water on the catalytically active centers. PMID- 11192097 TI - The synthesis and glass-forming properties of phthalocyanine-containing poly(aryl ether) dendrimers. AB - The synthesis, structural characterisation and properties of a number of phthalocyanine-containing dendrimers are described. Peripheral substitution of phthalocyanine (Pc) with four poly(aryl ether) dendritic wedges (1st, 2nd or 3rd generation) produces materials whose properties are dominated both by the columnar self-association of the Pc core and by the glass-forming character of the dendritic substituents. Asymmetric Pcs containing a single poly(aryl ether) dendron display a columnar mesophase, the structure of which can be frozen into an anisotropic glass at room temperature. Placing the dendritic wedges at the axial sites of silicon phthalocyanine prohibits self-association and gives materials from which can be fabricated robust, isotropic solid solutions of Pc with high glass transition temperatures. A single crystal X-ray diffraction analysis of one of these compounds illustrates the ability of the axial dendrons to prevent cofacial aggregation in the solid state. PMID- 11192098 TI - Strategies for the anchoring of metal complexes, clusters, and colloids inside nanoporous alumina membranes. AB - Two complementary strategies are presented for the anchoring of molecular palladium complexes, of cobalt or platinum clusters or of gold colloids inside the nanopores of alumina membranes. The first consists in the one step condensation of an alkoxysilyl functional group carried by the metal complex with the hydroxy groups covering the surface of the membrane pores. Thus, using the short-bite alkoxysilyl-functionalized diphosphane ligands (Ph2P)2N(CH2)3Si(OMe)3 (1) and (Ph2P)2N(CH2)4SiMe2(OMe)] (2) derived from (Ph2P)2NH (dppa) (dppa bis(diphenylphosphanyl)amine), the palladium complexes [Pd(dmba)(kappa2-P,P (Ph2P)2N(CH2)3Si(OMe)3)] Cl (3) and [Pd(dmba)[kappa2-P,P (Ph2P)2N(CH2)4SiMe2(OMe)]]Cl (4) (dmba-H = dimethylbenzylamine). respectively, were tethered to the pore walls. After controlled thermal treatment. confined and highly dispersed palladium nanoparticles were formed and characterized by transmission electron microscopy (TEM). This method could not be applied to the cobalt cluster [Co4(CO)8(mu-dppa)[mu-P,P-(Ph2P)2N(CH2)4SiMe2(OMe)]] (7) owing to its too limited solubility. However, its anchoring was achieved by using the second method which consisted of first derivatizing the pore walls with 1 or 2. The covalent attachment of the diphosphane ligands provides a molecular anchor that allows subsequent reaction with the cluster [Co4(CO)10(mu-dppa)] 6 to generate anchored 7 and this step was monitored by UV/Vis spectroscopy. In addition, the presence of carbonyl ligands in the cluster provides for the first time a very sensitive spectroscopic probe in the IR region which confirms both cluster incorporation and the retaining of its molecular nature inside the membrane. The presence of the bridging dppa ligand in 6 provides additional stabilization and accounts for the selectivity of the procedure. Using this method, platinum clusters (diameter ca. 2 nm) and gold colloids (diameter ca. 13 nm) were immobilized after passing their solution through the functionalized membrane pores. The resulting membranes were characterized by TEM which demonstrated the efficiency of the complexation and showed the high dispersion of the metal loading. The successful application of these methods has demonstrated that nanoporous alumina membranes are not only unique supports to incorporate metal complexes, clusters, or colloids but can also be regarded as functional matrices or microreactors, thus opening new fields for applications. PMID- 11192099 TI - Endometrial ablation: the next generation. PMID- 11192100 TI - The impact of maternal serum screening on the birth prevalence of Down's syndrome and the use of amniocentesis and chorionic villus sampling in South Australia. AB - OBJECTIVES: To describe the impact of maternal serum screening on the birth prevalence of Down's syndrome and on the use of amniocentesis and chorionic villus sampling in South Australia. DESIGN: A descriptive population-based study. SETTING: South Australia (population 1.48 million persons; approximately 20,000 births per year). PARTICIPANTS: Women who had births or terminations of pregnancy with Down's syndrome in 1982-1996, women who had maternal serum screening in 1991 1996, amniocentesis or chorionic villus sampling in 1986-1996. METHODS: Analysis of data from multiple sources on maternal serum screening, amniocentesis and chorionic villus sampling, births and terminations of pregnancy. MAIN OUTCOME MEASURES: Total prevalence and birth prevalence of Down's syndrome each year in 1982-1996; proportion of pregnant women using maternal serum screening in 1991 1996, and proportion using amniocentesis and chorionic villus sampling by indication in 1986-1996, by age group. RESULTS: Use of maternal serum screening for Down's syndrome increased from 17% when introduced in 1991 to 76% of women who gave birth in 1996. Between 1982 and 1986 and 1996, terminations of pregnancy for fetal Down's syndrome increased from 7.1 % to 75% and the birth prevalence of Down's syndrome fell by 60% from 1.05 to 0.42 per 1,000 births, against the background of an increase in total prevalence due to increasing maternal age. The use of amniocentesis increased from 5.8% in 1991 to 10.1% in 1996 mainly due to the increase among women younger than 35 years with maternal serum screening as the main reason. The increasing chorionic villus sampling rate among younger women stabilised at 0.4%, while the rate among older women decreased from 11.0% to 7.4%. CONCLUSIONS: The introduction of maternal serum screening in South Australia has resulted in increased use of any prenatal testing for Down's syndrome from about 7% (mainly older women having amniocentesis or chorionic villus sampling) to 84% of women (about 8% having direct amniocentesis or chorionic villus sampling and 76% having maternal serum screening first). This has resulted in a significant fall in the birth prevalence of Down's syndrome. maternal serum screening was the first indication of Down's syndrome for about half the terminations of pregnancy for Down's syndrome in 1993-1996, including three quarters of those in younger women. PMID- 11192101 TI - The prevalence of pelvic floor disorders and their relationship to gender, age, parity and mode of delivery. AB - OBJECTIVE: To define the prevalence of pelvic floor disorders in a non institutionalised community and to determine the relationship to gender, age, parity and mode of delivery. DESIGN: A representative population survey using the 1998 South Australian Health Omnibus Survey. SAMPLE: Random selection of 4400 households; 3010 interviews were conducted in the respondents' homes by trained female interviewers. This cross sectional survey included men and women aged 15 97 years. RESULTS: The prevalence of all types of self-reported urinary incontinence in men was 4.4% and in women was 35.3% (P<0.001). Urinary incontinence was more commonly reported in nulliparous women than men and increased after pregnancy according to parity and age. The highest prevalence (51.9%) was reported in women aged 70-74 years. The prevalence of flatus and faecal incontinence was 6.8% and 2.3% in men and 10.9% and 3.5% in women, respectively. Pregnancy (> 20 weeks), regardless of the mode of delivery, greatly increased the prevalence of major pelvic floor dysfunction, defined as any type of incontinence, symptoms of prolapse or previous pelvic floor surgery. Multivariate logistic regression showed that, compared with nulliparity, pelvic floor dysfunction was significantly associated with caesarean section (OR 2.5, 95% CI 1.5-4.3), spontaneous vaginal delivery (OR 3.4, 95% CI 2.4-4.9) and at least one instrumental delivery (OR 4.3, 95% CI 2.8-6.6). The difference between caesarean and instrumental delivery was significant (P<0.03) but was not for caesarean and spontaneous delivery. Other associations with pelvic floor morbidity were age, body mass index, coughing, osteoporosis, arthritis and reduced quality of life scores. Symptoms of haemorrhoids also increased with age and parity and were reported in 19.9% of men and 30.2% of women. CONCLUSION: Pelvic floor disorders are very common and are strongly associated with female gender, ageing, pregnancy, parity and instrumental delivery. Caesarean delivery is not associated with a significant reduction in long term pelvic floor morbidity compared with spontaneous vaginal delivery. PMID- 11192102 TI - Endocrinological and endometrial factors in recurrent miscarriage. AB - OBJECTIVE: To investigate the endocrinological and endometrial factors in women with unexplained recurrent miscarriage DESIGN: Prospective, case study SETTING: Recurrent miscarriage clinic, Jessop Hospital for Women, Sheffield PARTICIPANTS: One hundred and forty-four women with unexplained recurrent (> or =3) miscarriages METHODS: A blood sample was obtained in early follicular phase (day 3-5) to measure follicle stimulating hormone, luteinising hormone, prolactin, androgens and thyroid function; daily blood/urine samples were obtained from mid follicular phase to measure luteinising hormone until the luteinising hormone surge was identified; endometrial biopsy and a further blood sample for progesterone measurement were obtained in the mid-luteal phase. A transvaginal ultrasonography was performed to evaluate ovarian morphology. RESULTS: Hypersecretion of luteinising hormone or ultrasonographic features of polycystic ovarian disease was present in 8% and 7.8% of women, respectively. The free androgen index was elevated in 14.6% of subjects. In the mid-luteal phase, low progesterone level was found in 17.4% and delayed endometrial development was noted in 27.1% of women. Although women with recurrent miscarriage women and delayed endometrium had significantly lower progesterone levels than those with normal endometrial development, only 8/24 had mid-luteal progesterone levels below 30 nmol/L. Recurrent miscarriage was not associated with hyperprolactinaemia or abnormal thyroid function test. CONCLUSIONS: Endocrinological and endometrial abnormalities are present in about a quarter of women with unexplained recurrent miscarriage. PMID- 11192103 TI - Can glucose tolerance test predict fetal hyperinsulinism? AB - OBJECTIVE: To establish cut off levels for oral glucose tolerance test in pregnancy using fetal hyperinsulinism as a clinical endpoint. DESIGN: Capillary blood glucose levels at 0, 1, and 2 hours after the ingestion of either 1 g/kg or 75 g glucose, at 28 (SD 5) weeks of gestation were analysed in 220 women with elevated amniotic fluid insulin levels [> or =42 pmol/L (> or =7 microU/mL)] after a mean (SD) of 31 weeks (3) and in 220 nondiabetic controls. RESULTS: In women with elevated amniotic fluid insulin levels the mean (SD) capillary blood glucose values at 0, 1, and 2 hours were 5.2 mmol/L (1.0) [94 mg/dL (18)], 10.5 mmol/L (1.4) [189 mg/dL (25)] and 8.2 mmol/L (2.0) [147 mg/dL (36)], respectively. The one-hour value had the highest sensitivity to predict elevated amniotic fluid insulin levels. The 5th centile of the one-hour blood glucose levels representing a detection rate of 95% was 8.9 mmol/L (160 mg/dL). CONCLUSION: Glucose cut off levels in most established oral glucose tolerance test criteria are too high, to accurately predict amniotic fluid hyperinsulinism. A one-hour test may be sufficient for detecting amniotic fluid hyperinsulinism. Since different loads (1 g/kg, 75 g or 100 g) and blood fractions (venous plasma or capillary blood) have minimal impact on oral glucose tolerance test results, a single one-hour cut off of 8.9 mmol/L (160 mg/dL), independent of the sampling method, may be appropriate for the diagnosis of gestational diabetes mellitus severe enough to cause amniotic fluid hyperinsulinism. PMID- 11192104 TI - Hormonal regulation of neonatal weight: placental leptin and leptin receptors. AB - OBJECTIVE: To examine whether umbilical and maternal leptin levels correlate with birthweight, placental weight, and maternal weight; and to detect membrane-bound leptin receptors in placental tissue as well as soluble leptin receptors in umbilical and maternal blood. DESIGN: Prospective observational study. SETTING: University teaching hospital. METHODS: Serum levels of leptin and soluble leptin receptors were analysed in 31 randomly selected mother/newborn pairs at delivery. In addition, placental tissue was assayed for leptin receptors using immunocytochemistry and Western blot. RESULTS: The mean [SD] leptin level in umbilical cord venous blood (7.1 ng/mL [4.0]) was significantly lower (P<0.001) than in maternal blood (22.5 ng/mL [10.8]). Umbilical cord leptin concentrations correlated significantly with birthweight (P<0.001), placental weight (P<0.005) but not with maternal leptin. Maternal leptin concentrations correlated only with maternal weight (P<0.001). In chorionic villous tissue, trophoblasts stained strongly positive for leptin receptor-like immunoreactivity. Two membrane-bound isoforms of the leptin receptor were also detected in placental tissue. In both umbilical and maternal serum, a soluble leptin receptor was found migrating as broad band at Mr 97,000 D. CONCLUSION: The present data strongly reinforce the idea that circulating leptin levels may provide a growth-promoting signal for fetal development during late pregnancy. While membrane-bound leptin receptors may be involved in autocrine regulation of placental leptin production, the soluble receptor form may serve as a transport vehicle for leptin to fetal tissues. PMID- 11192105 TI - Accuracy and limitations of transabdominal fetal echocardiography at 12-15 weeks of gestation in a population at high risk for congenital heart disease. AB - OBJECTIVE: Evaluation of transabdominal fetal echocardiography at 12-15 weeks of gestation. DESIGN: Retrospective analysis. SETTING: Tertiary fetal cardiology unit. SAMPLE: Two hundred twenty-nine consecutive fetuses imaged at 12-15 weeks of gestation over a 45-month period. METHODS: Retrospective analysis of echocardiography and autopsy reports. MAIN OUTCOME MEASURES: Accuracy of early echocardiography for the detection of abnormalities of the cardiac connections. RESULTS: Diagnostic images were obtained in 226/229 fetuses (98.7%). Abnormalities of the cardiac connections were detected in 13 fetuses (5.7%) on the initial scan. Where information was available (n = 11), the echocardiographic findings were confirmed at autopsy or postnatally. In two of the 13 cases of congenital heart disease, repeat echocardiography was necessary to provide additional cardiological information. Of the 213 cases in whom a normal initial report was issued, four (1.7%) had congenital heart disease diagnosed later in pregnancy (n = 3) or postnatally (n = 1). Three of these fetuses had haemodynamically insignificant ventricular septal defects and one developed a dilated cardiomyopathy later in gestation. CONCLUSIONS: Transabdominal fetal echocardiography can be performed at 12-15 weeks of gestation permitting accurate early detection of major congenital heart defects in a high risk population. Some forms of congenital heart disease, usually minor, may not be detectable at such an early stage. PMID- 11192106 TI - RhD genotyping by quantitative fluorescent polymerase chain reaction: a new approach. AB - OBJECTIVE: To develop a new method of RhD/d genotype determination using a quantitative fluorescent PCR (QF-PCR) assay. METHODS: Polymerase chain reaction amplification (PCR) of fragments of exon 7 of both the RHD and RHCE genes was performed from 32 amniotic fluid and 26 chorionic villus samples known to be heterozygous for the RHD gene, 74 peripheral blood samples of RhD-positive blood donors (homozygous or heterozygous) estimated by serologic typing and 24 RhD negative fetal samples. The number of copies of the RHD gene in RhD-positive samples was determined by comparing the fluorescent intensities of the amplification products specific for the RHD and the RHCE genes. RESULTS: A ratio of fluorescent intensities of 1:1 clearly indicated D/D homozygous individuals whereas a ratio of 1:2 was demonstrated in samples from D/d heterozygous individuals. The mean fluorescent intensity ratio of the peak areas of homozygous samples was 1.12 (SD 0.128), the mean ratio of the peak areas of heterozygous samples was 0.51 (SD 0.060). Complete agreement was obtained between RhD/d typing by QF-PCR and RhD genotypes assessed by family studies and serological methods. CONCLUSIONS: The fluorescent PCR-based DNA test allows easy, rapid and accurate determination of the zygosity for the RHD gene. This new technique provides useful information for the clinical management of pregnancies of sensitised RhD negative mothers. PMID- 11192107 TI - Hepatitis C virus load during pregnancy and puerperium. AB - OBJECTIVE: To assess whether pregnancy and delivery influence serum levels of hepatitis C virus (HCV) in carrier mothers. DESIGN: A prospective study. SETTING: University department of obstetrics and gynaecology. PARTICIPANTS: Ten pregnant HCV carriers (group A) and 8 nonpregnant HCV carriers (group B). METHODS: Serum samples were collected for group A at first and third trimesters, delivery, postpartum 1, 3, 6, 9 and 12 months, and at every three months for 1 year for group B. MAIN OUTCOME MEASURES: Each serum sample was tested for serum alanine aminotransferase (ALT), anti-HCV titre and HCV-cDNA concentration by a competitive polymerase chain reaction (PCR) with a sensitivity of 250 copies/mL serum. RESULTS: In group A, the HCV levels remained unremarkably changed during pregnancy and delivery. However, all women had decreased HCV levels 1 and 3 months after delivery. Two women had undetectable serum HCV level postpartum and thereafter. Serum ALT values in 3 women were sporadically elevated, but did not correlate with decreased serum HCV levels. Anti-HCV titres remained unchanged during the study period. In two women from group B, the serum HCV levels were undetectable during follow up. Other 6 women showed fluctuations in the serum HCV levels but all were above 250 copies/mL. Serum ALT values were normal and anti HCV titres remained stationary in all 8 nonpregnant carriers. CONCLUSION: Serum HCV levels are decreased 1 and 3 months after delivery. This fact might suggest that puerperium is an optimal time for antiviral therapy in HCV carrier mothers. PMID- 11192108 TI - Qualitative study of pregnancy and childbirth experiences in Somalian women resident in Sweden. AB - OBJECTIVE: To explore the attitudes, strategies and habits of Somalian immigrant women related to pregnancy and childbirth, in order to gain an understanding as to how cultural factors might affect perinatal outcome. METHODS: Interpreter assisted qualitative in depth interviews around topics such as attitudes and strategies regarding childbirth. PARTICIPANTS: Fifteen women from the Somalian community in a city in Sweden, between the ages of 20 and 55 years with delivery experience in Somalia and Sweden. RESULTS: The interviews describe how the women themselves perceived their experiences of childbirth in the migrant situation. Many voluntarily decreased food intake in order to have a smaller fetus, an easier delivery and to avoid caesarean section. The participants considered a safe delivery to be the same as a normal vaginal delivery They reduced food intake in order to diminish the growth of the fetus, thereby avoiding caesarean section and mortality. The practice of food intake reduction, while rational for the participants when in Somalia, was found less rational in Sweden and may lead to suboptimal obstetric surveillance. CONCLUSIONS: Somalian women have childbirth strategies that differ from those of Swedish women. These strategies should be seen as 'survival behaviours' related to their background in an environment with high maternal mortality. The hypothesis generated is that there is a relationship between the strategies during pregnancy and adverse perinatal outcome among Somalian immigrants. Considering the strong association of the habits to safe birth, it seems doubtful whether the women will change their habits as long as health care providers are unaware of their motives. We suggest a more culturally sensitive perinatal surveillance. PMID- 11192109 TI - Folate affects apoptosis in human trophoblastic cells. AB - Effects of folate deficiency on the rate of apoptosis in human cytotrophoblastic cells has been investigated. Apoptosis was determined in cytotrophoblastic cells after culture in 1. control medium, 2. folate-free medium and 3. folate-free medium plus 10% fetal calf serum. Apoptosis rates in cells cultured in mediums 2 and 3 were significantly higher than those cultured in the control medium (P<0.02 and P<0.03, respectively). In conclusion, human cytotrophoblastic cells show a significantly increased rate of apoptosis in vitro after culture in a folate-free medium. Possible explanations for the association between folate deficiency and pregnancy complications are suggested. PMID- 11192110 TI - Congenital chylothorax in siblings. PMID- 11192111 TI - Acute lumbar intervertebral disc prolapse: a complication of the lithotomy position. PMID- 11192112 TI - Theory of DNA electrophoresis: a look at some current challenges. AB - Although electrophoresis is one of the basic methods of the modern molecular biology laboratory, new ideas are being suggested at an accelerated rate, in large part because of the pressing demands of the biomedical community. Although we now have, at least for some methods, a fairly good theoretical understanding of the physical mechanisms that lead to the observed peak spacings, widths and shapes, this knowledge is often too qualitative to be used to guide further technical developments and improvements. In this article, we review some selected elements of the current state of our theoretical ignorance, focusing mostly on DNA electrophoresis, and we offer several suggestions for further theoretical investigations. PMID- 11192113 TI - Dispersive phenomena in electromigration separation methods. AB - A review on dispersive effects and on peak broadening in electromigration separation methods (capillary electrophoresis and electrochromatography) is presented, mainly covering papers published between the beginning of 1997 and the beginning of 2000. Most attention is drawn to work dealing with nonlinear effects that cause anomalous electromigration dispersion in electrolyte systems with two or multiple coions. Further, topics cover the comparison of electroosmotic and pressure-driven modes in electrochromatography, dispersive effects due to nonhomogeneous velocity fields in packed electrochromatography columns, to nonuniform electroosmotic flow, to sorption of analytes (mainly proteins) at the column wall or the stationary phase, and due to the influence of the nonideal column geometry like coiling or irregularities in shape. PMID- 11192114 TI - Recent progress in capillary isotachophoresis. AB - This article is a continuation of previous reviews and summarizes the progress of analytical capillary isotachophoresis in the years 1997-1999. Papers reviewed include theoretical and methodological aspects as well as analytical applications. Included are also papers using isotachophoresis and/or isotachophoretic principles as part of multidimensional separation schemes. PMID- 11192115 TI - Recent advances in affinity capillary electrophoresis. AB - Use of the specificity of (bio)interactions can effectively overcome the selectivity limitation faced in capillary electrophoresis (CE), and the resulting technique usually is referred to as affinity capillary electrophoresis (ACE). Despite the high selectivity of ACE, several important problems still need to be addressed. A major issue in all CE separations, including ACE, is the concentration detection limit. Using UV detection, this is usually in the order of 10(-6) M whereas laser-induced fluorescence (LIF) detection can provide detection limits down to the sub-10(-10) M range. However, a marked disadvantage of LIF is that labeling of the analytes is usually required, which might change the interaction behavior of the solutes under investigation. Additionally, labeling reactions at sub-10(-10) M concentration levels are certainly not trivial and often difficult to perform quantitatively. Alternative and universal detection approaches, particularly mass spectrometric (MS) detection, look very promising but (A) CE-MS techniques are still far from routine application. Important future progress in sensitive detection strategies is likely to increase the use of ACE in the future. PMID- 11192116 TI - Capillary electrophoresis-based immunoassays. AB - This review covers the progress and developments in the field of capillary electrophoresis immunoassay (CEIA) over the past three years. Because many excellent descriptions of the principles of these methods are available (e.g., in the reviews listed in this article), no elementary introduction is given to the field of immunoassays (IAs) or CEIAs. This report focuses exclusively on experimental results, dividing the CEIA papers into the categories of direct, indirect, and microchip electrophoretic immunoassays. In the last section, a brief summary of the current status of the CEIA field is presented. PMID- 11192117 TI - Recent developments in electrokinetically driven analysis on microfabricated devices. AB - This review is devoted to the rapid developments in the field of microfluidic separation devices in which the flow is electrokinetically driven, and where the separation element forms the heart of the system, in order to give an overview of the trends of the last three years. Examples of microchip layouts that were designed for various application areas are given. Optimization of mixing and injection strategies, designs for the handling of multiple samples, and capillary array systems show the enormous progress made since the first proof-of-concept papers about lab-on-a-chip devices. Examples of functional elements for on-chip preconcentration, filtering, DNA amplification and on-chip detection indicate that the real integration of various analytical tasks on a single microchip is coming into reach. The use of materials other than glass, such as poly(dimethylsiloxane) and polymethylmethacrylate, for chip fabrication and detection methods other than laser-induced fluorescence (LIF) detection, such as mass spectrometry and electrochemical detection, are described. Furthermore, it can be observed that the separation modes known from capillary electrophoresis (CE) in fused-silica capillaries can be easily transferred to the microchip platform. The review concludes with an overview of applications of microchip CE and with a brief outlook. PMID- 11192118 TI - Ultrathin-layer gel electrophoresis of biopolymers. AB - Emerging need for large-scale, high-resolution analysis of biopolymers, such as DNA sequencing polymerase chain reaction, (PCR) product sizing, single nucleotide polymorphism (SNP) hunting and analysis of protein molecules necessitated the development of automated and high-throughput gel electrophoresis based methods enabling rapid, high-performance separations in a wide molecular weight range. Scaling down electric field mediated separation processes supports higher throughput due to the applicability of higher voltages, thus speeding up analysis time. Indeed, efforts in miniaturization resulted in faster, easier, less costly and more convenient analyses, fulfilling the needs of the emerging biotechnology industry for microscale and massively parallel assays. The two primary approaches in miniaturizing electrophoresis dimensions are the capillary and microslab formats. This latter one evolved towards ultrathin-layer gel electrophoresis which is, except from the thickness of the separation platform, slightly in the upper side of the scale, resulting in considerably easier handling. Ultrathin layer gel electrophoresis combines the advantages of conventional slab-gel electrophoresis (multilane format) and capillary gel electrophoresis (rapid, high efficiency separations). It is readily automated, automatic versions of it have been extensively used for large-scale DNA sequencing in the Human Genome Project and more recently became popular in high throughput DNA fragment analysis. Ultrathin-layer techniques are the first step towards the wider use of electrophoresis microchips in perfecting a user-friendly interface between the user and the microdevice. PMID- 11192119 TI - Recent progress in capillary electrochromatography. AB - Capillary electrochromatography (CEC) continues to captivate many separation scientists. A remarkable activity is apparent from the numerous publications in the literature using CEC. A review of the most recent progress in CEC is presented herein, covering an extensive fraction of the literature on CEC published from the year 1997 until the beginning of 2000. Most of the recent developments have concentrated on column technology. PMID- 11192120 TI - Nonaqueous capillary electrophoresis: a versatile completion of electrophoretic separation techniques. AB - Nonaqueous capillary electrophoresis (NACE) is the application of a conductive electrolyte dissolved in either one organic solvent or a mixture of several organic solvents to carry out zone electrophoresis or related techniques in fused silica capillaries. A complete review on the fundamentals, the optimization of analytical methods, practical considerations, and applications is given. To explain the differences to CE in aqueous media, a brief summary on solvent properties and molecular interactions in solutions introduces the reader into these fields. The use of additives to tune separation selectivity by means beyond a pure zone-electrophoretic mechanism is discussed in detail for organic media. Special detection techniques providing high potential for NACE are presented. Data on the precision of NACE methods and a list of relevant applications are included. More specialized applications like the determination of physicochemical constants in NACE or the setup of a semipreparative mode are described. PMID- 11192121 TI - Recent advances in electrochemical detection in capillary electrophoresis. AB - Recent advances in the design and application of electrochemical (EC) detection systems in capillary electrophoresis (CE) are reviewed, with the objective of providing the nonelectrochemist with a state-of-the-art picture of CEEC instrumentation and an overview of the principal analytes for which CEEC is best suited. The detection schemes considered here include those based both on amperometry and on potentiometry as both kinds of EC systems are being actively developed in CE and have the potential for broad application in analysis. Over the three-year period covered by this review, an important direction that CEEC has taken is the construction of more complex electrode systems beginning with the use of multiple EC electrodes and culminating with the adaptation of EC detection to microfabricated "lab-on-a-chip" analysis devices. In addition, CEEC applications have now grown to include a broad variety of inorganic, organic, and biochemical analytes and samples. PMID- 11192122 TI - Derivatization trends in capillary electrophoresis. AB - This survey gives an overview of recent derivatization protocols, starting from 1996, in combination with capillary electrophoresis (CE). Derivatization is mainly used for enhancing the detection sensitivity of CE, especially in combination with laser-induced fluorescence. Derivatization procedures are classified in tables in pre-, on- and postcapillary arrangements and, more specifically, arranged into functional groups being derivatized. The amine and reducing ends of saccharides are reported most frequently, but examples are also given for derivatization of thiols, hydroxyl, carboxylic, and carbonyl groups, and inorganic ions. Other reasons for derivatization concern indirect chiral separations, enhancing electrospray characteristics, or incorporation of a suitable charge into the analytes. Special attention is paid to the increasing field of research using on-line precapillary derivatization with CE and microdialysis for in vivo monitoring of neurotransmitter concentrations. The on capillary derivatization can be divided in several approaches, such as the at inlet, zone-passing and throughout method. The postcapillary mode is represented by gap designs, and membrane reactors, but especially the combination of separation, derivatization and detection on a chip is a new emerging field of research. This review, which can be seen as a sequel to our earlier reported review covering the years 1991-1995, gives an impression of current derivatization applications and highlights new developments in this field. PMID- 11192123 TI - Capillary electrophoresis of peptides and proteins in isoelectric buffers: an update. AB - Capillary electrophoresis in acidic, isoelectric buffers is a novel methodology allowing fast protein and peptide analysis in uncoated capillaries. Due to the low pH adopted and to the use of dynamic coating with cellulose derivatives, silanol ionization is essentially suppressed and little interaction of macromolecules with the untreated wall occurs. In addition, due to the low conductivity of quasi-stationary, isoelectric buffers, high-voltage gradients can be applied (up to 800 V/cm) permitting fast peptide analysis with a high resolving power due to minimal diffusional peak spreading. Four such buffers are here described: cysteic acid (Cys-A, pI 1.85), iminodiacetic acid (IDA, pI 2.23), aspartic acid (Asp, pI 2.77) and glutamic acid (Glu, pI 3.22). A number of applications are reported, ranging from food analysis to the study of folding/unfolding transitions of proteins. PMID- 11192124 TI - Polymeric and polymer-supported pseudostationary phases in micellar electrokinetic chromatography: performance and selectivity. AB - Several types of synthetic ionic polymers have been employed as pseudostationary phases in electrokinetic chromatography. The polymers have been shown to have some significant advantages and different chemical selectivity relative to conventional surfactant micelles. Polymeric phases are effective for the separation and analysis of hydrophobic and chiral compounds, and may be useful for the application of mass spectrometric detection. Additionally, the polymeric phases often demonstrate unique selectivity relative to micellar phases, and can be designed and synthesized to provide desired selectivity. This review covers efforts to develop and characterize the performance, characteristics, and selectivity of synthetic polymeric pseudostationary phases since their introduction in 1992. Some ideas for the future development of polymeric pseudostationary phases and the role they may play in electrokinetic separations are presented. PMID- 11192125 TI - Capillary electrochromatography with physically and dynamically absorbed stationary phases. AB - Adsorption is always considered a troublesome effect in capillary electrophoresis (CE) and capillary electrochromatography (CEC). However, the adsorption effect can also be exploited to prepare or optimize the stationary phase in CEC. Compared with the chemical synthesis of new stationary phase materials for CEC, this method is simpler and more convenient. This review is focused on CEC with physically and dynamically adsorbed stationary phases. Separation of some acidic, basic and neutral solutes as well as enantiomers in CEC with dynamically adsorbed stationary phases are presented. The theory for the migration of charged solutes and the stationary phases currently used in CEC are also briefly reviewed. PMID- 11192126 TI - Polymeric matrices for DNA sequencing by capillary electrophoresis. AB - We review the wide range of polymeric materials that have been employed for DNA sequencing separations by capillary electrophoresis. Intensive research in the area has converged in showing that highly entangled solutions of hydrophilic, high molar mass polymers are required to achieve high DNA separation efficiency and long read length, system attributes that are particularly important for genomic sequencing. The extent of DNA-polymer interactions, as well as the robustness of the entangled polymer network, greatly influence the performance of a given polymer matrix for DNA separation. Further fundamental research in the field of polymer physics and chemistry is needed to elucidate the specific mechanisms by which DNA is separated in dynamic, uncross-linked polymer networks. PMID- 11192128 TI - Recent progress in enantiomer separation by capillary electrochromatography. AB - Enantiomer separation by electrochromatography (CEC) can be performed in three modes: (i) open-tubular capillary electrochromatography (o-CEC), in which the chiral selector is physically adsorbed coated, and thermally immobilized or covalently attached to the internal capillary wall; (ii) packed capillary electrochromatography (p-CEC), in which the capillary is either filled with chiral modified silica particles or with an achiral packing material, and a chiral selector is added to the mobile phase; and (iii) monolithic (rod) capillary electrochromatography (rod-CEC) in which the chiral stationary phase (CSP) consists of a single piece of porous solid. We present an overview on methods and new trends in the field of electrochromatographic enantiomer separation such as CEC with either nonaqueous mobile phases or stationary phases with incorporated permanent charges, or with packing beds consisting of nonporous silica particles or particles with very small internal diameters. PMID- 11192127 TI - Recent progress in chiral separation principles in capillary electrophoresis. AB - This review summarizes recent developments in the field of chiral separations by electromigration techniques including capillary zone electrophoresis (CZE), capillary gel electrophoresis (CGE), isotachophoresis (ITP), electrokinetic chromatography (EKC), and capillary electrochromatography (CEC). This overview focuses on the development of new chiral selectors and the introduction of new techniques rather than applications of already established selectors and methods. The mechanisms of the different chiral separation principles are discussed. PMID- 11192129 TI - Enantioseparations using capillary electromigration techniques in nonaqueous buffers. AB - This review summarizes recent developments in the field of enantioseparations in capillary electromigration techniques using nonaqueous background electrolytes. The more established and rather intensively reviewed field of nonaqueous chiral capillary electrophoresis (NAQ-CE) is covered in less detail whereas more attention is paid to the relatively new field of nonaqueous capillary electrochromatography (NAQ-CEC). PMID- 11192130 TI - Recent progress in capillary electrophoresis of metal ions. AB - Advances in the fundamental studies and methodology of capillary electrophoresis (CE) as applied to metal ion analysis over the last two years are reviewed, with the objective of providing the interested reader with a state-of-the-art picture of technique's potentialities in the area. In particular, novel strategies for separation selectivity control and CE system innovations designed to enhance the detection sensitivity are described. In addition, a brief overview of the primary metal analytes and samples for which the technique appears to be best suited is given. The current limitations of the technique regarding most of all the implementation for routine use are considered along with the approaches on how they could be addressed. Finally, some pointers as to the likely trends in the future research are discussed. PMID- 11192131 TI - Safety profile and tolerability of amprenavir in the treatment of adult and pediatric patients with HIV infection. AB - BACKGROUND: Amprenavir (APV) is a new HIV-I protease inhibitor used in combination with other antiretroviral agents for the treatment of HIV-1 infection. OBJECTIVE: The aim of this study was to assess the safety profile and tolerability of APV. METHODS: A review of data from 358 adults enrolled in 2 phase III, randomized, 48-week, controlled studies and from 268 children enrolled in 1 phase II and 1 phase III study was conducted. The adult data were collected between February 25, 1997, and April 1, 1999. Data were collected in children from September 10, 1997, to January 15, 1999; these data were collected before completion of either study. Adults and children who had and had not been treated previously with antiretroviral agents were enrolled. In these studies, APV was used in combination with 2 nucleoside reverse transcriptase inhibitors. RESULTS: The most common drug-related adverse events in patients receiving APV were gastrointestinal events and oral/perioral paresthesia. The majority of adverse events were mild or moderate in intensity, early in onset, and transient. Nausea (27/358 patients, 8%), vomiting (15/358, 4%), rash (11/358, 3%), and diarrhea/loose stools (9/358, 3%) were the most common adverse events associated with treatment discontinuation. Severe laboratory abnormalities possibly related to APV were rare. In children, the nature and frequency of adverse events were similar to those in adults. Metabolic complications were infrequent in APV studies to date; symptoms related to fat redistribution were reported in <3% of patients treated with APV. Lipid or glucose laboratory abnormalities were reported with similar frequency in the APV and control groups in both studies in adults. CONCLUSIONS: In the clinical trials reviewed, APV was generally well tolerated when administered with other antiretroviral agents in adult and pediatric patients with HIV infection. PMID- 11192132 TI - Pioglitazone hydrochloride in combination with metformin in the treatment of type 2 diabetes mellitus: a randomized, placebo-controlled study. The Pioglitazone 027 Study Group. AB - BACKGROUND: Their complimentary mechanisms of action suggest that a combination of pioglitazone hydrochloride and metformin may have clinically beneficial effects in the treatment of patients with type 2 diabetes. OBJECTIVE: This study was undertaken to assess the efficacy and tolerability of pioglitazone in combination with metformin in patients with type 2 diabetes mellitus. METHODS: This was a 16-week, double-blind study with the option of enrollment in a separate open-ended, open-label study. It included patients with poorly controlled diabetes mellitus (glycated hemoglobin [HbA1c] > or =8.0%, fasting C peptide >1.0 ng/mL) who had been receiving a stable regimen of metformin for > or =30 days. Patients with diabetic retinopathy, nephropathy, or neuropathy; impaired liver or kidney function; or unstable cardiovascular or cerebrovascular conditions were excluded. Patients were randomized to receive once-daily pioglitazone 30 mg + metformin or placebo + metformin. Patients in the open-label extension received pioglitazone 30 mg (with optional titration to 45 mg) + metformin. RESULTS: Three hundred twenty-eight patients were randomized to treatment (168 pioglitazone + metformin, 160 placebo + metformin), and 249 completed the study. Of these, 154 elected to enter the open-label extension study. Patients' mean age was 56 years; most (84%) were white and slightly more than half (57%) were male. Patients receiving piogli- tazone 30 mg + metformin had statistically significant mean decreases in HbA1c (-0.83%) and fasting plasma glucose (FPG) levels (-37.7 mg/dL) compared with placebo + metformin (P < or = 0.05). Decreases in FPG levels occurred as early as the fourth week of therapy, the first time point at which FPG was measured. The pioglitazone + metformin group had significant mean percentage changes in levels of triglycerides (-18.2%) and high-density lipoprotein cholesterol (+8.7%) compared with placebo + metformin (P < or = 0.05). Mean percentage increases were noted in low-density lipoprotein cholesterol levels (7.7%, pioglitazone + metformin; 11.9%, placebo + metformin) and total cholesterol (4.1%, pioglitazone + metformin; 1.1%, placebo + metformin), with no significant differences between groups. In the extension study, patients treated with open-label pioglitazone + metformin for 72 weeks had mean changes from baseline of -1.36% in HbA1c and -63.0 mg/dL in FPG. The incidence of adverse events was similar in both groups. Throughout the study, no patient in either treatment group had an alanine aminotransferase (ALT) value > or =3 times the upper limit of normal, a commonly used marker of potential liver damage. Thus, no evidence of drug-induced hepatotoxicity or drug-induced elevations in serum ALT was observed. CONCLUSIONS: In this study in patients with type 2 diabetes mellitus, pioglitazone + metformin significantly improved HbA1c and FPG levels, with positive effects on serum lipid levels and no evidence of drug-induced hepatotoxicity. These effects were maintained for >1.5 years, including the open-label extension. PMID- 11192133 TI - Phase III, randomized, double-blind study of clarithromycin extended-release and immediate-release formulations in the treatment of patients with acute exacerbation of chronic bronchitis. AB - BACKGROUND: Clarithromycin has an established efficacy and safety profile in the treatment of respiratory tract infections. OBJECTIVE: The purpose of this study was to compare the clinical and bacteriologic efficacy and tolerability of clarithromycin extended-release and immediate-release formulations in patients with acute exacerbation of chronic bronchitis (AECB). METHODS: In a phase III, randomized, double-blind, parallel-group, multicenter study. patients aged > or =12 years with signs and symptoms of AECB and a productive cough with purulent sputum received treatment with extended-release (two 500-mg tablets once daily) or immediate-release (one 500-mg tablet twice daily) clarithromycin for 7 days. Assessments were performed before treatment, within 48 hours after treatment, and at the test-of-cure visit (study days 19-21). Patients who took > or =1 dose of study drug were included in the safety analysis. RESULTS: Of 620 patients randomized and treated, 182 were clinically and bacteriologically assessable (100 in the extended-release group and 82 in the immediate-release group). Treatment groups were well matched with respect to demographic characteristics and medical and social history. At the test-of-cure visit, 83% (83/100) of patients in the extended-release and 82% (67/82) of patients in the immediate-release group achieved clinical cure; 86% (85/99) and 85% (70/82), respectively, demonstrated bacteriologic cure. Overall pathogen eradication rates were 86% (100/116) in the extended-release group and 88% (86/98) in the immediate-release group. The most frequently reported adverse events were diarrhea (6% in extended-release group vs 4% in immediate-release group; no significant difference), taste alterations (4% in each group), and nausea (3% in each group); no clinically meaningful changes in laboratory values or vital signs, as assessed by the investigator, were observed. CONCLUSION: This study suggests that clarithromycin extended-release and immediate-release formulations have equivalent clinical and bacteriologic efficacy and tolerability in patients with AECB. PMID- 11192134 TI - Phase III, randomized, double-blind study of clarithromycin extended-release and immediate-release formulations in the treatment of adult patients with acute maxillary sinusitis. AB - BACKGROUND: Clarithromycin has an established bacteriologic efficacy and safety profile in the treatment of respiratory tract infections. OBJECTIVE: This study compares the efficacy and tolerability of extended-release and immediate-release formulations of clarithromycin in patients with acute maxillary sinusitis. METHODS: Fourteen days' treatment with once-daily clarithromycin was compared with the immediate-release, twice-daily formulation in a phase III, randomized, double-blind, parallel-group, multicenter study. Patients aged > or =12 years with signs, symptoms, and a radiologically confirmed diagnosis of acute maxillary sinusitis were eligible. Patients were assessed before treatment, within 48 hours after treatment, on study days 16 to 18, and at the test-of-cure visit on study days 24 to 31. Patients who received > or =1 dose of study drug were included in the safety analysis. RESULTS: Of 283 patients treated, 245 were included in the efficacy analysis (122 in the extended-release group, 123 in the immediate release group). Treatment groups were well matched with respect to demographic characteristics and medical condition and history. At the test-of-cure visit, 85% of patients in the clarithromycin extended-release group and 79% in the immediate release group were deemed clinical cures; 89% and 91% in the extended-release and immediate-release groups, respectively, demonstrated radiographic success. Overall incidences of study drug-related adverse events were similar in the 2 treatment groups (32% in the extended-release group and 28% in the immediate release group); however, significantly fewer patients receiving extended-release clarithromycin (2/142 11%]), compared with those receiving the immediate-release formulation (10/141 [7%]: P = 0.02) discontinued therapy because of drug-related gastrointestinal symptoms or abnormal taste. No clinically meaningful changes in laboratory values or vital signs were observed during the study. CONCLUSION: Although the efficacy of the 2 formulations was comparable, once-daily clarithromycin extended-release was better tolerated than the twice-daily immediate-release formulation by patients with acute maxillary sinusitis. PMID- 11192135 TI - Rechallenge of patients who had discontinued alendronate therapy because of upper gastrointestinal symptoms. AB - BACKGROUND: There have been reports from physicians in clinical practice that up to 30% of patients taking bisphosphonate therapy develop upper gastrointestinal (UGI) symptoms, many or most of which they assume to be related to the drug. However, in several large placebo-controlled clinical trials of bisphosphonates, the incidence of UGI symptoms has been > or =30%, even among patients receiving placebo, perhaps reflecting a high background incidence of UGI events in osteoporotic patients. OBJECTIVE: To assess the relationship between alendronate treatment and UGI complaints in patients who had discontinued treatment with alendronate in clinical practice because of UGI symptoms, we compared the incidence of such events on rechallenge with alendronate or placebo. METHODS: This was a multicenter, double-blind trial in which postmenopausal women with osteoporosis who had previously discontinued alendronate therapy because of a UGI adverse experience were randomized to daily treatment with either alendronate 10 mg or matching placebo (1:1 ratio) for 8 weeks. The primary end point was the cumulative incidence of discontinuations due to any UGI adverse experience. Secondary end points were the incidence of any clinical adverse experiences and the percentage change from baseline in urinary N-telopeptide adjusted for urinary creatinine at week 8. RESULTS: A total of 172 women were included in the study. They were a mean of 20.9 years past menopause, ranging in age from 41 to 90 years (mean, 67.0 years); 90.7% were white. On rechallenge, 14.8% (13/88) of patients in the alendronate group and 16.7% (14/84) in the placebo group discontinued treatment because of UGI adverse experiences. CONCLUSION: The results of this study suggest that many UGI adverse experiences reported during therapy with alendronate may reflect a high background incidence of UGI complaints and an increased sensitivity to detection of such complaints, rather than a causal relationship to therapy. PMID- 11192136 TI - Pharmacokinetics, pharmacodynamics, and relative pharmacokinetic/pharmacodynamic profiles of zaleplon and zolpidem. AB - OBJECTIVE: This study compared the pharmacokinetics, pharmacodynamics, and pharmacokinetic/pharmacodynamic (PK/PD) profile of zaleplon, a new pyrazolopyrimidine hypnotic, with those of zolpidem and placebo. METHODS: This was a double-blind, 5-period crossover study in which healthy volunteers with no history of sleeping disorder were randomized to 10- or 20-mg oral doses of zaleplon, 10- or 20-mg oral doses of zolpidem, or placebo. The pharmacokinetic characteristics of the active drugs were estimated using a noncompartmental method and NONMEM. Pharmacodynamic characteristics were determined using psychophysical tests, including measures of sedation, mood, mental and motor speed, and recent and remote recall. Results of these tests were used to compare the drugs' relative PK/PD profiles. RESULTS: Ten healthy male and female volunteers, aged 23 to 31 years, took part in the study. The apparent elimination half-life of zaleplon (60.1+/-8.9 min) was significantly shorter than that of zolpidem (124.5+/-37.9 min) (P < 0.001). Zaleplon produced less sedation than zolpidem at the 2 doses studied (P < 0.001). The sedation scores of the zaleplon groups returned to baseline in less time than those of the zolpidem groups (4 vs 8 hours; P < 0.05). Zaleplon had no effect on recent or remote recall, whereas zolpidem had a significant effect on both measures (P < 0.05). CONCLUSIONS: In this study in 10 young, healthy volunteers, zaleplon was eliminated more rapidly, produced no memory loss, and caused less sedation than zolpidem at the same doses. PMID- 11192137 TI - Comparison of the clinical efficacy and comfort of olopatadine hydrochloride 0.1% ophthalmic solution and nedocromil sodium 2% ophthalmic solution in the human conjunctival allergen challenge model. AB - BACKGROUND: Mast cell stabilizers, such as the ocular antiallergic agent nedocromil sodium 2% ophthalmic solution, are not rapid acting and often require a loading period of > or =2 weeks for maximal efficacy. Olopatadine hydrochloride 0.1% ophthalmic solution is a member of a new class of topical antiallergic agents that have combined antihistaminic and mast cell-stabilizing properties. OBJECTIVE: The purpose of this study was to compare the clinical efficacy and comfort of olopatadine with those of nedocromil in the conjunctival allergen challenge model. METHODS: This was a single-center, 3-visit, randomized, double masked, contralaterally controlled study. Seventy-five subjects with a history of allergic conjunctivitis were screened, and the 52 who responded to conjunctival allergen challenge at visits I and 2 were randomized by eye to receive olopatadine, nedocromil, or placebo (a "natural tears" lubricant eye drop). Because nedocromil may require a 2-week loading period for maximal efficacy, the eyes assigned to that agent received nedocromil for 14 days (between visits 2 and 3), whereas the eyes assigned to olopatadine or placebo received placebo during this period. Throughout the loading phase, subjects instilled 1 drop of the assigned masked medication in each eye twice daily. At the assessment visit (visit 3), subjects received I drop of masked olopatadine, nedocromil, or placebo in each eye and were asked to rate the comfort of each drop on a scale from 0 to 8. Fifteen minutes after instillation of medication, subjects were challenged with the allergen concentration that had elicited a positive conjunctival allergic response at the previous visits. Subjects then scored their itching on a scale from 0 to 4 at 3, 5, and 10 minutes after challenge. Mean itching scores for all eyes were compared by treatment. Paired t tests were performed on the mean itching and ocular comfort scores at each time point. At the end of the study, subjects were asked which treatment they preferred in terms of comfort and efficacy. RESULTS: Forty-nine subjects completed the study. Forty eyes received olopatadine, 36 received nedocromil, and 22 received placebo. Olopatadine was clinically and statistically superior to nedocromil at reducing itching in the conjunctival allergen challenge model (mean unit difference: -1.60 at 3 minutes, 1.68 at 5 minutes, -1.19 at 10 minutes; P < 0.001). One drop of olopatadine was more efficacious than 29 drops of nedocromil. Olopatadine-treated eyes were rated as being significantly more comfortable than nedocromil-treated eyes (0.73 vs 1.55; P = 0.034). Of the 14 subjects treated with olopatadine and nedocromil who stated a preference, 10 (71%) were more satisfied with olopatadine than with nedocromil. CONCLUSION: In the conjunctival allergen challenge model, olopatadine was more efficacious and comfortable than nedocromil in reducing the itching associated with allergic conjunctivitis. PMID- 11192138 TI - Treatment of hypertension in patients > or =65 years of age: experience with amlodipine. AB - BACKGROUND: Hypertension is a common finding in patients > or =65 years of age that contributes to cardiovascular morbidity and mortality, but many patients are untreated or their hypertension inadequately controlled. Recent randomized controlled studies have demonstrated the benefits of treating hypertension in the elderly. OBJECTIVE: This study was undertaken to assess the efficacy and tolerability of amlodipine, a long-acting calcium channel blocker, in elderly (> or =65 years of age) patients with mild to moderate hypertension (diastolic blood pressure 95 to 114 mm Hg). METHODS: This was an open-label, multicenter, 10-week, general-practice study involving patients >18 years of age. Patients with malignant or secondary hypertension or unstable angina were excluded, as were those who had experienced an acute myocardial infarction or stroke in the preceding 3 months or had been treated with an alpha-blocker in the preceding 6 months. Patients were assigned to 1 of 4 treatment schedules: amlodipine monotherapy or combination therapy and amlodipine given once daily in the morning or in the evening. Approximately 50% of patients would receive a morning dose, and approximately 80% would receive amlodipine as monotherapy. The paired t test was used to assess the significance of differences from baseline values, with significance set at P < 0.05. RESULTS: A total of 5135 patients received amlodipine and were included in the tolerability analysis. Of these, 3511 of 3628 patients (96.8%) <65 years and 1471 of 1507 patients (97.6%) > or =65 years (including 336 of 349 [96.3%] > or =75 years) were included in the efficacy analysis. Significant reductions (P < 0.05) in blood pressure were noted in all groups after 4 and 8 weeks of treatment. The equivalence of efficacy in all age groups was seen in terms of reduction in blood pressure (reduction of 21/15 mm Hg in patients <65 years of age, 25/16 mm Hg in those > or =65 years of age, and 26/17 mm Hg in those > or =75 years of age) compared with baseline. Therapy was successful in 2878 patients (82.0%) <65 years of age, in 1238 patients (84.2%) > or =65 years of age, and in 284 patients (84.5%) > or =75 years of age. The incidence of adverse events was similar in all age groups (18.0%, <65 years; 22.3%, > or =65 years; and 24.1%, > or =75 years), with no statistically significant differences between groups. Tolerability was rated as good or excellent in all patients, with no significant differences between groups. CONCLUSIONS: Once-daily amlodipine was effective in the treatment of mild to moderate hypertension in this patient population and demonstrated a low frequency of adverse events, a high degree of tolerability, and improved well-being. Morning rather than evening dosing appeared to confer a slight advantage. PMID- 11192140 TI - Effect of citalopram on plasma levels of oral theophylline. AB - BACKGROUND: Citalopram and theophylline may be prescribed together to treat patients with depression and asthmatic disease. Because theophylline has a low therapeutic index, small changes in plasma levels may result in therapeutic failure or adverse effects. Both citalopram and theophylline are metabolized by cytochrome P450 (CYP) isozymes. Theophylline is metabolized by CYP1A2; however, the extent to which citalopram interacts with this isozyme in vivo is not known. OBJECTIVE: This study was conducted to investigate whether citalopram alters plasma levels of oral theophylline. METHODS: In an open-label, multiple-dose study, healthy nonsmoking volunteers 18 to 45 years of age were administered a single oral dose of theophylline (300 mg) on day 1. Beginning on day 3, citalopram 40 mg was administered daily through day 24 to achieve steady-state plasma levels. On day 23 a single oral dose of theophylline 300 mg was coadministered with citalopram 40 mg. Fasting plasma levels of theophylline were measured on day 1 (in the absence of citalopram) and on day 23 (in the presence of steady-state plasma concentrations of citalopram) periodically for 36 hours. RESULTS: Thirteen subjects (8 men and 5 women) participated; all completed the study. One subject was not included in the pharmacokinetic calculations. Citalopram treatment had no effect on the pharmacokinetic characteristics of theophylline. CONCLUSIONS: Citalopram dosing to steady state did not inhibit or induce the metabolism of theophylline in this population of healthy volunteers. Dose adjustment of theophylline thus may not be necessary in patients receiving concurrent therapy with citalopram. PMID- 11192139 TI - Regional lung deposition of a technetium 99m-labeled formulation of mometasone furoate administered by hydrofluoroalkane 227 metered-dose inhaler. AB - BACKGROUND: A new inhaled suspension formulation of mometasone furoate (MF), a potent corticosteroid with minimal systemic availability, has been developed for the treatment of asthma. This formulation is delivered by metered-dose inhaler (MDI) using the nonchlorofluorocarbon propellant hydrofluoroalkane 227 (HFA-227). OBJECTIVE: The primary goal of this study was to determine the respiratory tract deposition of this formulation of MF. A secondary objective was to measure plasma concentrations of MF and a putative metabolite, 6-X-OH MF, to determine the systemic exposure to corticosteroid. METHODS: This was a single-dose, open-label study in which 200 microg of technetium 99m (99mTc)-radiolabeled MF was administered to patients with asthma. Gamma scintigraphy was used to quantify lung, oropharyngeal, stomach, and MDI mouthpiece deposition patterns of MF. RESULTS: Eleven patients, aged 21 to 47 years, with a history of asthma were enrolled in and completed the study. The mean (+/- SD) whole lung deposition of MF was 13.9%+/-5.7% of the metered (ex-valve) dose. The central lung zone received 5.3%+/-2.8% of the dose; the intermediate zone received 4.7%+/-1.9%; and peripheral lung deposition was 4.0%+/-1.5%. The mean (+/- SD) ratio of peripheral to central lung deposition was 0.8+/-0.2. Oropharyngeal deposition was 79.1%+/ 8.7% of the ex-valve dose, with 6.3%+/-7.8% deposited on the MDI mouthpiece and 0.7%+/-0.5% exhaled. The majority of plasma samples taken for analysis of MF and 6-13-OH MF concentrations were below the limit of quantification (50 pg/mL) in all patients after inhalation of 200 microg 99mTc-labeled ME CONCLUSION: The lung deposition of MF when administered via HFA-227 MDI is comparable to the 10 to 20% lung deposition seen with other corticosteroid suspension for- mulations administered by MDI that have demonstrated effectiveness in the treatment of asthma. PMID- 11192141 TI - Meta-analysis of the effect of latanoprost and brimonidine on intraocular pressure in the treatment of glaucoma. AB - OBJECTIVE: The purpose of this study was to indirectly quantify and compare the intraocular pressure (IOP)-lowering effects of latanoprost and brimonidine eye drops at baseline and after 3 and 6 months in the treatment of primary open-angle glaucoma. METHODS: This meta-analysis combined data from all randomized controlled trials comparing the effects on IOP of latanoprost and brimonidine treatment in adults with a baseline IOP > or =20 mm Hg. MEDLINE and EMBASE were searched for reports of the ophthalmic administration of either drug versus the other, placebo, or active therapy. Included studies reported IOP as either means or differences (with SD or SE) and sample sizes. A random-effects model was used to pool data within each drug group. As a proxy for success rates, area under the curve (AUC) was calculated for the proportion of patients having an IOP <20 mm Hg. RESULTS: One hundred fifty-five articles reporting on 158 trials were identified; 147 papers were rejected (141 were not randomized controlled trials, 5 were duplicates, and 1 had nonextractable data), leaving 9 trials from 8 articles. A total of 2152 patients were included in the meta-analysis: 597 received latanoprost, 571 received brimonidine, and the remainder received timolol or betaxolol. Baseline IOPs were similar in patients randomized to latanoprost or brimonidine (25.3 and 24.6 mm Hg, respectively). At 3 months, latanoprost and brimonidine reduced IOP by 8.4 and 6.5 mm Hg, respectively (P = 0.004 latanoprost vs brimonidine), and at 6 months by 8.0 and 6.2 mm Hg, respectively (P = 0.045). AUC was 0.834 and 0.675 at 3 months for latanoprost and brimonidine, respectively, and 0.817 and 0.715 at 6 months, respectively (both, P < 0.001). CONCLUSIONS: This indirect comparison of data from the available randomized clinical trials showed latanoprost to be statistically superior to brimonidine in reducing IOP in adults with primary open-angle glaucoma. Additional long-term, head-to-head comparisons of the efficacy, safety, and cost of latanoprost and brimonidine are needed to support and supplement these findings. PMID- 11192142 TI - Duration of effect of botulinum toxin type A in adult patients with cervical dystonia: a retrospective chart review. AB - BACKGROUND: Clinical trials have established the efficacy and safety of botulinum toxin type A (BTX-A) in patients with cervical dystonia. To maintain the clinical benefits of BTX-A, injections need to be repeated whenever patients' symptoms begin to recur. OBJECTIVE: The purpose of this study was to determine, in clinical practice settings, the mean duration of effect of BTX-A in the treatment of adult patients with cervical dystonia. METHODS: A retrospective chart review was undertaken at an academic center and a private neurology practice. At each site, > or =50 patients being treated for cervical dystonia were identified and randomized for chart review. Patients had to have received the first assessable injection of BTX-A between January 1, 1998, and March 31, 1998, to coincide with the clinical availability of the most current formulation of the neurotoxin. A chart was eligible for review if the patient was aged > or =18 years, had a documented diagnosis of idiopathic cervical dystonia, was being treated with BTX A, and had been under the continuous care of investigators from January 1, 1998, to August 31, 1999. Of the 102 patients initially identified, the first 30 from each site who met the study inclusion criteria were assessed for (1) age and sex; (2) severity of dystonia; (3) years of BTX-A use; (4) dates of first, second, third, and fourth BTX-A injections; (5) drug dose; (6) use of electromyography; (7) use of other prescribed therapies; (8) laboratory tests; and (9) adverse events. The mean interval between each visit and mean per-patient duration of effect were calculated and stratified by patient characteristics. RESULTS: The mean age of the patients was 56.4 years. Two thirds of the patients were women. Forty-one of the 60 patients (68.3%) had either moderate or severe disease, and 48 (80.0%) had experienced cervical dystonia for >5 years. The mean per-patient duration of effect across the 4 visits was 15.5 weeks (range, 12.2-24.3 weeks). The duration of effect did not differ significantly between study sites despite the differences in disease severity, drug dose, and use of adjunctive therapy. CONCLUSION: BTX-A the controls symptoms of cervical dystonia for 12 to 24 weeks, with a mean duration of effect per patient of 15.5 weeks. PMID- 11192143 TI - Pharmacokinetic comparison of oral solution and tablet formulations of citalopram: a single-dose, randomized, crossover study. AB - BACKGROUND: Citalopram tablets fulfill most dosing needs in the treatment of depression, but some patients may have difficulty swallowing tablets and thus may be less likely to comply with their medication regimen. A liquid formulation of citalopram could be beneficial for such patients. OBJECTIVE: This study was undertaken to compare the pharmacokinetic profiles of oral solution and tablet formulations of citalopram in healthy volunteers. METHODS: In this open-label, single-dose, randomized, crossover, bioequivalence study, healthy volunteers alternately received one 60-mg dose of citalopram as an oral solution (10 mg/5 mL) and one 60-mg dose as a tablet. Doses were separated by a 14-day interval. RESULTS: Of 24 subjects enrolled (mean age 27 years), 24 (16 men and 8 women) received the citalopram oral solution and 23 (15 men and 8 women) received the tablet; 1 subject discontinued before receiving the tablet. Citalopram was rapidly absorbed, with peak plasma concentrations occurring at approximately 4 hours with both formulations. The rate and extent of absorption were similar between the 2 formulations, and no statistically significant differences were observed in half-life or oral clearance between formulations. Similarly, the pharmacokinetic profile for demethylcitalopram (the major metabolite of citalopram) did not differ between the 2 formulations. Both formulations were well tolerated, with no serious adverse events reported. CONCLUSION: The oral solution and tablet formulations of citalopram 60 mg were determined to be bioequivalent in this population. PMID- 11192144 TI - One-year tolerability and efficacy of sumatriptan nasal spray in adolescents with migraine: results of a multicenter, open-label study. AB - OBJECTIVE: The objective of this study was to determine the 1-year tolerability and efficacy of sumatriptan nasal spray (NS) at doses of 5, 10, and 20 mg for the treatment of acute migraine in adolescents. METHODS: This was a prospective, multicenter, open-label, 1-year, multiple-attack study. Adolescents (aged 12-17 years) with a > or =6-month history of migraine with or without aura, 2 to 8 moderate or severe migraines per month, and a typical migraine duration of > or =4 hours were eligible for participation. After initial treatment with sumatriptan 10 mg, the dose could be adjusted down to 5 mg or up to 20 mg at the investigator's discretion to optimize tolerability or efficacy. Patients could treat an unlimited number of moderate or severe migraine attacks, provided there was a 24-hour headache-free period between treated attacks and a 2-hour period between doses of sumatriptan NS. A second dose of sumatriptan NS was available for headache recurrence 2 to 24 hours after initial treatment; no more than 2 doses could be used within a 24-hour period. Adverse events, vital signs, electrocardiographic and physical findings, and laboratory variables were assessed. Headache response (reduction of moderate/severe predose pain to mild/no pain) and pain-free response (reduction of moderate/severe predose pain to no pain) were reported by patients 2 hours after dosing. RESULTS: A total of 437 patients treated > or =1 migraine; 3272 total attacks were treated, with 3675 drug exposures (mean, 1.1 dose/attack). Patients had a mean age of 14.1 years, 91% were white, and 53% were female. Seven patients used the 5-mg dose; meaningful conclusions concerning this dose could not be made. Drug-related adverse events were reported in 33% of attacks with the 10-mg dose and 31% with the 20-mg dose; most were related to taste disturbance. Adverse events did not increase with a second dose or over time. Four percent (16/437) of patients withdrew due to drug-related adverse events. One serious adverse event, a facial nerve ischemic event (10-mg dose), was considered drug related. No drug-related changes in vital signs or electrocardiographic findings were observed. Headache response 2 hours after dosing was reported by 76% of patients taking the 10-mg dose and 72% of those taking the 20-mg dose. Pain-free response 2 hours after dosing was reported by 43% and 40% of patients in the 10- and 20-mg groups, respectively. CONCLUSIONS: Based on these results, sumatriptan NS at doses of 10 and 20 mg was well tolerated and effective in the 1-year treatment of multiple migraine attacks in adolescents. PMID- 11192145 TI - Use of the term elderly in the scientific literature. PMID- 11192146 TI - Rivastigmine for Alzheimer's disease: Canadian interpretation of intermediate outcome measures and cost implications. AB - BACKGROUND: Clinical studies have shown that patients with Alzheimer's disease (AD) who are treated with rivastigmine have statistically significantly better scores on 5 scales used to assess AD than control patients receiving placebo. However, the clinical meaning and cost implications of these differences are not clear. OBJECTIVE: The purpose of this study was to assess the clinical meaning and cost implications of statistically significant results obtained in clinical trials of rivastigmine for the treatment of AD. Potential cost implications for the health care system, caregivers, and society are considered. METHODS: Data on clinical effects of rivastigmine were obtained from published North American and European clinical studies of patients with mild to moderately severe AD receiving rivastigmine 6 to 12 mg/d (n = 828) or placebo (n = 647). Differences in scores on the Alzheimer's Disease Assessment Scale-Cognitive Function, Clinician's Interview-Based Impression of Change with both clinical and caregiver information considered, Progressive Deterioration Scale, Mini-Mental State Examination (MMSE), and Global Deterioration Scale were assessed. A convenience panel of 9 Canadian specialists experienced in the treatment of AD provided their opinions on the clinical importance of the trial results. Chart review was performed to identify specific behaviors that improved, and cost implications of improvements were assessed. RESULTS: The panel determined that statistically significant differences in scores on all scales except the MMSE were likely associated with functional or cognitive differences that were clinically relevant for patients, reflecting stabilization that would have beneficial consequences for caregivers and health care resource use. Subsequent chart review showed that improvement on specific scale items confirmed the physician panel's opinion. Analysis of possible cost implications to society indicated that medication expenditures would be offset largely by delays in the need for paid home care and institutionalization, positive effects on caregiver health, and less time lost from work for the caregiver. CONCLUSIONS: From the perspective of a Canadian specialist panel, rivastigmine treatment for AD produces clinically relevant effects for patients that are beneficial to caregivers. These effects suggest decreased use of caregiver resources and delays in the need for institutionalization, both of which reduce societal costs. PMID- 11192147 TI - Cost-efficacy comparison of inhaled fluticasone propionate and budesonide in the treatment of asthma. AB - BACKGROUND: The results of a recent meta-analysis comparing 2 inhaled corticosteroids, fluticasone propionate (FP) and budesonide, demonstrated that FP had an improved efficacy-to-safety ratio compared with budesonide. However, limited data are available on the relative economic benefits of these 2 regimens. OBJECTIVE: This pharmacoeconomic analysis used individual patient data from studies in the meta-analysis to compare the relative cost-efficacy of 2 asthma regimens from the perspective of a US third-party payer. METHODS: This analysis included all 7 studies in the meta-analysis that compared budesonide with FP dosed at approximately half the dose of budesonide and that included measurement of daily morning peak expiratory flow (PEF). RESULTS: The total daily per-person cost of asthma management was higher for patients treated with budesonide than with FP ($3.00 vs $2.25, respectively). Treatment with FP had greater cost efficacy than treatment with budesonide, based on a range of outcome measures that included improvement in morning PEF, symptom-free days, and episode-free days. The daily cost per effectively treated patient (an increase in PEF of > or = 10%) was $5.62 with FP and $10.05 with budesonide. The cost per symptom-free day was $4.36 with FP, compared with $6.67 with budesonide. The cost per episode free day was $5.60 with FP and $9.42 with budesonide. The pharmacoeconomic difference continued to favor FP as the criteria for success were made more stringent and the cost of budesonide was lowered. CONCLUSION: Based on data from the 7 randomized, controlled trials, treatment of asthma with FP was more effective and less expensive, using US health care assumptions and costs, than treatment with budesonide. PMID- 11192148 TI - Trends in the rate of depressive illness and use of antidepressant pharmacotherapy by ethnicity/race: an assessment of office-based visits in the United States, 1992-1997. AB - OBJECTIVE: This study was undertaken to determine ethnicity/race-specific (white, black, and Hispanic) population-adjusted rates of US office-based physician visits in which a diagnosis of a depressive disorder was recorded or in which a diagnosis of a depressive disorder was recorded and antidepressant pharmacotherapy was prescribed. METHODS: Data from the National Ambulatory Medical Care Survey for 1992 through 1997 were partitioned into three 2-year periods: 1992-1993, 1994-1995, and 1996-1997. For each 2-year period, data from office-based physician visits for patients aged 20 to 79 years were extracted to assess, by ethnicity/race, (1) the number of visits in which a diagnosis of a depressive illness was recorded (International Classification of Diseases, Ninth Revision, Clinical Modification codes 296.2-296.36, 300.4, or 311) and (2) the number of visits in which a diagnosis of a depressive illness was recorded and antidepressant pharmacotherapy was prescribed. We calculated ethnicity/race specific rates (per 100 US population aged 20 to 79 years) of office-based visits in which a diagnosis of a depressive disorder was recorded and in which a diagnosis of a depressive disorder was recorded and antidepressant pharmacotherapy was prescribed. The specialty of the reporting physician and the proportion of patients receiving a selective serotonin reuptake inhibitor (SSRI) were also discerned. RESULTS: From 1992-1993 to 1996-1997, the rate of office based visits (per 100 US population aged 20 to 79 years) in which a diagnosis of a depressive disorder was recorded increased 3.7% for whites (from 10.9 to 11.3; P = 0.001), 31.0% for blacks (from 4.2 to 5.5; P = 0.001), and 72.9% for Hispanics (from 4.8 to 8.3; P = 0.001). The rate of office-based visits in which a diagnosis of a depressive disorder was recorded and antidepressant pharmacotherapy was prescribed increased 18.5% for whites (from 6.5 to 7.7 per 100; P = 0.001), 38.5% for blacks (from 2.6 to 3.6 per 100; P = 0.001). and 106.7% for Hispanics (from 3.0 to 6.2 per 100; P = 0.001). Between 1992-1993 and 1996-1997, use of an SSRI increased among whites and blacks (from 50.0% to 65.8% and from 40.5% to 58.2%, respectively), but declined among Hispanics (from 51.4% to 48.6%; all comparisons P = 0.001). CONCLUSION: By 1996-1997, the population adjusted rates for Hispanics were within a quartile of those observed for whites, whereas the rates for blacks remained at less than half those observed in whites. The observed divergence in population-adjusted rates by ethnicity/race may reflect the nature of the patient-physician relationship, sensitivity and specificity of diagnostic techniques and instruments, and the wider social context in which an office-based visit occurs, including access to and type of health insurance and coverage for mental health services. PMID- 11192149 TI - Treatment strategies for gastroesophageal reflux disease. PMID- 11192150 TI - Stacking in capillary zone electrophoresis. AB - Due to the short light path of the capillaries, the CE detection limit based on concentration, is far less than that of HPLC and not sufficient for many practical applications. Several methods, based on different electrophoretic maneuvers, can concentrate the sample (stack) easily on the capillary before the separation step of capillary zone electrophoresis (CZE). These methods incorporate different types of discontinuous buffers as the means for invoking different velocities to the same analyte molecules to produce a sharpening of the band (stacking). In CZE, these buffers can be often very simple such as sample dilution or adding to the sample a high concentration of a fast mobility ion. However, in other applications these buffers can be as complicated as those required for isotachophoresis. Stacking can often yield a concentration factor of 5-30-fold, which can improve greatly in CZE the detection limits bringing them very close to those of HPLC. Different methods of stacking, the importance of discontinuous buffers and the different mechanism for concentration on the capillary are reviewed here. As there is a need for more practical applications, there will be more methods devised for stacking in CZE. PMID- 11192151 TI - Sample stacking of cationic and anionic analytes in capillary electrophoresis. AB - The behavior of charged species along concentration boundaries in capillary zone electrophoresis (CZE) that was first described in detail by Everaerts et al. in 1979 assured the possibility of concentrating charged solutes inside the capillary. The concentration effect is based on the sudden change in analyte electrophoretic velocity brought about by the difference in the magnitude of the electric field. Furthermore, this on-line method could be the needed solution to the problem of low concentration sensitivity in CZE. Sample stacking, which is now its well known name, has then found valuable use in applying CZE in many fields, especially after the in-depth studies performed in the early 90s by Chien and Burgi. This article reviews the theory and methodological developments of sample stacking developed for charged analytes in CZE and also in electrokinetic chromatography. A table conveying the reported applications especially in the biomedical and environmental fields is given. On top of this, other on-line concentration methods for charged species, namely, sample self-stacking, acetonitrile stacking, sweeping, cation selective exhaustive injection-sweeping, and use of a pH junction, are briefly discussed. PMID- 11192153 TI - Solid-phase microextraction in biomedical analysis. AB - Chromatographic methods are preferred in the analysis of organic molecules with lower molecular mass (<500 g/mol) in body fluids, i.e., the assay of drugs, metabolites, endogenous substances and poisons as well as of environmental exposure by gas chromatography (GC) and liquid chromatography (LC), for example. Sample preparation in biomedical analysis is mainly performed by liquid-liquid extraction and solid-phase extraction. However, new methods are investigated with the aim to increase the sample throughput and to improve the quality of analytical methods. Solid-phase microextraction (SPME) was introduced about a decade ago and it was mainly applied to environmental and food analysis. All steps of sample preparation, i.e., extraction, concentration, derivatization and transfer to the chromatograph, are integrated in one step and in one device. This is accomplished by the intelligent combination of an immobilized extraction solvent (a polymer) with a special geometry (a fiber within a syringe). It was a challenge to test this novel principle in biomedical analysis. Thus, an introduction is provided to the theory of SPME in the present paper. A critical review of the first applications to biomedical analyses is presented in the main paragraph. The optimization of SPME as well as advantages and disadvantages are discussed. It is concluded that, because of some unique characteristics, SPME can be introduced with benefit into several areas of biomedical analysis. In particular, the application of headspace SPME-GC-MS in forensic toxicology and environmental medicine appears to be promising. However, it seems that SPME will not become a universal method. Thus, on-line SPE-LC coupling with column switching technique may be a good alternative if an analytical problem cannot be sufficiently dealt with by SPME. PMID- 11192152 TI - Solid-phase trapping of solutes for further chromatographic or electrophoretic analysis. AB - Because of its simplicity, speed and effectiveness, solid-phase extraction (SPE) has become the preferred technique for concentration of selected analytes prior to chromatographic or electrophoretic analysis. In this review the historical development of SPE is briefly traced. Then the principles of SPE are reviewed in some detail. Numerous references are given on the format, sorbents, elution conditions, online techniques and automation with special emphasis on relatively recent developments. The principles and recent advances in solid-phase microextraction (SPME) are also reviewed. The final section on selected recent applications includes an extensive list of references to work published within the last three years. Future trends and developments are discussed briefly. PMID- 11192154 TI - Microextraction of drugs. AB - This review will attempt to provide an overview as well as a theoretical and practical understanding of the use of microextraction technologies for drug analysis. The majority of the published reports to date focus on the use of fibre solid-phase microextraction and so the review is significantly focused on this technology. Other areas of microextraction such as single drop and solvent film microextraction are also described. Where there are insufficient examples in the literature to illustrate important concepts, examples of non-drug analyses are presented. The review is intended for readers new to the field of microextraction or its use in drug extraction, but also provides an overview of the most recent advances in the field which may be of interest to more experienced users. Particular emphasis is placed on the effect various sample matrices have on extraction characteristics. PMID- 11192155 TI - Analytical applications of membrane extraction in chromatography and electrophoresis. AB - An overview of the analytical applications of membrane-based systems for sample enrichment in chromatography and capillary electrophoresis is presented. A brief introduction to the different types of membranes and the main forces related to the transport through them is also given. PMID- 11192156 TI - Membrane-based techniques for sample enrichment. AB - Sample preparation techniques based on non-porous membrane extraction generally offer a high degree of selectivity and enrichment power, together with convenient possibilities for direct and automated connections to chromatographic and other analytical instruments. In this review principles and applications for techniques as supported liquid membrane extraction, microporous membrane liquid-liquid extraction, polymeric membrane extraction and membrane extraction with a sorbent interface are described and compared. PMID- 11192157 TI - Analytical-scale microwave-assisted extraction. AB - Microwave-assisted extraction (MAE) is a process of using microwave energy to heat solvents in contact with a sample in order to partition analytes from the sample matrix into the solvent. The ability to rapidly heat the sample solvent mixture is inherent to MAE and the main advantage of this technique. By using closed vessels the extraction can be performed at elevated temperatures accelerating the mass transfer of target compounds from the sample matrix. A typical extraction procedure takes 15-30 min and uses small solvent volumes in the range of 10-30 ml. These volumes are about 10 times smaller than volumes used by conventional extraction techniques. In addition, sample throughput is increased as several samples can be extracted simultaneously. In most cases recoveries of analytes and reproducibility are improved compared to conventional techniques, as shown in several applications. This review gives a brief theoretical background of microwave heating and the basic principles of using microwave energy for extraction. It also attempts to summarize all studies performed on closed-vessel MAE until now. The influences of parameters such as solvent choice, solvent volume, temperature, time and matrix characteristics (including water content) are discussed. PMID- 11192158 TI - Surfactant cloud point extraction and preconcentration of organic compounds prior to chromatography and capillary electrophoresis. AB - The use of preconcentration steps based on phase separation by the cloud point technique offers a convenient alternative to more conventional extraction systems. It has been used successfully for the preconcentration of species of widely differing character and nature, such as metal ions, proteins and other biomaterials, or organic compounds of strongly differing polarity. Here we address the most recent analytical applications of this methodology when used as an isolation and trace enrichment step prior to the analysis of organic compounds (polycyclic aromatic hydrocarbons, polychlorinated compounds, pesticides, phenolic derivatives, aromatic amines, vitamins, etc.) via liquid and gas chromatography or capillary electrophoresis. PMID- 11192159 TI - Headspace solid-phase microextraction procedures for gas chromatographic analysis of biological fluids and materials. AB - Solid-phase microextraction (SPME) is a new solventless sample preparation technique that is finding wide usage. This review provides updated information on headspace SPME with gas chromatographic separation for the extraction and measurement of volatile and semivolatile analytes in biological fluids and materials. Firstly the background to the technique is given in terms of apparatus, fibres used, extraction conditions and derivatisation procedures. Then the different matrices, urine, blood, faeces, breast milk, hair, breath and saliva are considered separately. For each, methods appropriate for the analysis of drugs and metabolites, solvents and chemicals, anaesthetics, pesticides, organometallics and endogenous compounds are reviewed and the main experimental conditions outlined with specific examples. Then finally, the future potential of SPME for the analysis of biological samples in terms of the development of new devices and fibre chemistries and its coupling with high-performance liquid chromatography is discussed. PMID- 11192160 TI - Preconcentration of contaminants in water analysis. AB - Among the environmental areas, in this review attention will be focused on water matrices and both on organic (e.g., pesticides, herbicides, phenols, polycyclic aromatic hydrocarbons), inorganic species and anion pollutants, since these kinds of substances include a wide number of compounds with different physical and chemical properties and different effects on human health. Analytical methods for control of quality of waters are required to be highly specific and possibly highly sensitive for the determination of even low amounts of pollutants. The main problems encountered during the analysis are the separation of matrix components from the pollutants of interest and the achievement of low detection limits. Therefore an overview on different materials and techniques available for sample concentration and/or matrix removal will be provided and discussed according to the chemical characteristics of the pollutant that has to be enriched. PMID- 11192161 TI - Chemically modified polymeric sorbents for sample preconcentration. AB - Solid-phase extraction is an attractive alternative in sample preparation because it overcomes many drawbacks of liquid-liquid extraction and makes on-line determination possible by hyphenation with chromatographic techniques. Driven by the need for more effective and more selective sorbents, advances in solid-phase extraction include the development of new materials. This paper describes different types of chemically modified sorbents for the solid-phase extraction of compounds from aqueous samples. Chemical introduction of different functional groups into a polymeric resin improves the efficiency of solid-phase extraction by providing better surface contact with the aqueous samples; also, these sorbents have a greater capacity than the typical solid-phase materials for polar compounds have. The most important new sorbents are the chemically modified resins based on styrene-divinylbenzene copolymers. Preparation of these new sorbents is described, and advantages and drawbacks of off-line procedures and on line procedures are also discussed. Applications for off-line and on-line chromatographic determinations of polar compounds are presented. PMID- 11192162 TI - Solid-phase extraction coupling to capillary electrophoresis with emphasis on environmental analysis. AB - This article reviews the status of solid-phase extraction (SPE) coupled with capillary electrophoresis (CE). It focuses on some of the organic pollutants which have captured the interest of analytical chemists--phenols, surfactants, dyes, polynuclear aromatic hydrocarbons (PAHs), aromatic and aliphatic amines, aromatic acids and aromatic sulfonic acids--and, in particular, on monitoring pesticides from different sources. It shows that the coupling of SPE to CE has considerable potential in the analysis of environmental pollutants. PMID- 11192163 TI - Liquid-liquid extraction procedures for sample enrichment in capillary zone electrophoresis. AB - This review article presents an overview of applications of liquid-liquid extraction (LLE) for analyte enrichment and clean-up of samples prior to capillary zone electrophoresis (CZE). The basic principles of LLE are discussed with special emphasis on analyte enrichment. In addition, attention is focused on the requirements for the final extract to be compatible with CZE. The paper discusses selected examples from the literature with special emphasis on detection limits in drug analysis and in environmental chemistry. Finally, the paper focus on alternative liquid-phase extraction concepts based on electroextraction, supported liquid membranes, and liquid-phase microextraction. PMID- 11192164 TI - Effect of temperature and flow-rate on analysis of basic compounds in high performance liquid chromatography using a reversed-phase column. AB - The peak shape and retention of some basic probes together with a neutral reference compound were investigated as a function of temperature and flow-rate using a reversed-phase HPLC column at both pH 3.0 and pH 7.0. The retention of bases often showed an anomalous increase with temperature; retention mechanisms are complex as shown by studies of the effect of buffer cation concentration on retention. Considerable improvements in column efficiency for bases may result from operation at elevated temperature. Improvements did not seem attributable either to incidental changes in the retention factor, or (in this particular study where low sample masses were utilised) to the influence of sample load. The optimum flow-rate for highest efficiency is generally lower for basic compounds than neutrals, and due to the steepness of the Van Deemter curves obtained, high flow-rates appear to be particularly detrimental in the chromatography of basic compounds. PMID- 11192165 TI - Test to evaluate countercurrent chromatographs. Liquid stationary phase retention and chromatographic resolution. AB - Countercurrent chromatography (CCC) is a liquid chromatography (LC) technique with a special column able to retain a liquid stationary phase while the liquid mobile phase is pumped through. The coil planet centrifuge machines are made of open tube wound on spools. A simple test is proposed. The methanol-water (90:10, v/v)-heptane biphasic system is used with heptane as the mobile phase in the ascending or tail-to-head mode. The methanol-water stationary phase retention volume is measured at different flow-rates and rotor rotation speeds. After every machine equilibration, an alkylbenzene mixture is injected and the retention factors, peak efficiencies and resolution factors are measured or calculated for each solute. The wealth of information contained in the data set obtained is demonstrated. Four coil planet centrifuge machines of very different characteristics and one hydrostatic CCC machine with channels and ducts were submitted to the test. It was shown that the Sf, stationary retention factor, obtained with these machines was linearly dependent on the square root of F, the mobile phase flow-rate [Q. Du, C. Wu, G. Qian, P. Wu, Y. Ito, J. Chromatogr. A 835 (1999) 231-235]. It is shown that the slopes of the Sf versus F(1/2) lines could be related to a minimum rotor rotation, omega(mini), necessary to obtain the hydrodynamic equilibrium. The Sf and F parameters give the mobile phase linear velocity, u. It is shown that u is proportional to the square root of omega, the rotor rotation speed. The slope and intercept of the latter relationship also result in an omega(mini) value coherent with the first one. With the peak efficiencies and chromatographic resolution factors obtained for toluene and hexylbenzene, the parameters: number of plates per tubing turn, machine volume for one plate, and tubing length for one plate, were calculated and compared for the five machines. The internal diameter of the tubing used is shown to be a critical parameter acting on the machine volume and number of tubing turns. PMID- 11192166 TI - Ion chromatography detector based on solid-state ion-selective electrode array. AB - A variety of neutral carrier type ionophores for monovalent cations were employed to prepare solid-state cation-selective electrodes (SSEs) for use as a detector in single-column ion chromatography (IC). The polyurethane-based pseudoreference electrode made it possible to assemble an array type SSE detector for IC. An SSE based detector provides not only the overall chromatogram for the separated ion species (monensin methyl ester-nonactin-based membrane), but also the enhanced chromatogram for specified ions of interest (valinomycin as K+ and nonactin for NH4+). This feature makes it possible to perform highly quantitative analysis with low detection limits even if the separation efficiency of the ion-exchange is not sufficient. Since SSE-based IC detectors are easily miniaturized and replaceable at low cost, they are an ideal component of a portable IC system. PMID- 11192167 TI - Enantiomeric separation of some pharmaceutical intermediates and reversal of elution orders by high-performance liquid chromatography using cellulose and amylose tris(3,5-dimethylphenylcarbamate) derivatives as stationary phases. AB - Several pairs of enantiomers of pharmaceutical intermediates were separated by HPLC directly on cellulose and amylose tris(3,5-dimethylphenylcarbamate) derivatives (Chiralcel OD and Chiralpak AD) using hexane as mobile phase with 2 propanol or ethanol as modifier. The separation and elution order of the enantiomers on the two columns using different alcohol modifiers were compared. Reversal of the elution order of some enantiomeric pairs associated with increased retention of many of these solutes upon changing the mobile phase modifier from 2-propanol to ethanol was observed. The effect of structural variation of two pairs of enantiomers on their k' and separation factor alpha was noted. Chiralcel OD and Chiralpak AD columns provided different retention, separation and elution order of some of the enantiomeric pairs. PMID- 11192168 TI - Micelle formation for improvement of continuous subcritical water extraction of polycyclic aromatic hydrocarbons in soil prior to high-performance liquid chromatography-fluorescence detection. AB - A new method for the extraction-individual separation-determination of polycyclic aromatic hydrocarbons (PAHs) in soil is reported. The method is based on the integration of three steps: continuous subcritical extraction, solid-phase clean up/preconcentration, and HPLC separation with post-column fluorimetric determination. Sodium dodecyl sulfate (SDS) was added to the water for favouring the extractability of the low-polarity analytes. Soil samples spiked with the target PAHs were subjected to static-dynamic extraction with SDS-water at 50 bar, 150 degrees C, for 15 min of static extraction and 10 min dynamic extraction at a flow-rate of 3 ml/min. Recoveries from 73.6 to 110.4% were obtained in the presence of SDS versus 30 to 80% obtained with water as extractant. The calibration graphs provided by HPLC-fluorimetric detection were run between 0.031 and 0.375 microg/ml for each analyte with regression coefficients between 0.917 and 0.999 and precision, expressed as RSD, between 1.2 and 11.5%. The method was applied to a certified reference material [CRM 524, BCR (Community Bureau of Reference), industrial soil/organic] for validation and the results obtained were in agreement with the certified values. PMID- 11192169 TI - Negative atmospheric pressure chemical ionisation low-energy collision activation mass spectrometry for the characterisation of flavonoids in extracts of fresh herbs. AB - The flavonoid composition of commonly eaten fresh herbs such as dill, oregano and parsley was analysed by combined LC, MS and low-energy collision induced dissociation (CID) MS-MS. Negative atmospheric pressure chemical ionisation (APCI) MS and MS-MS were used to provide molecular mass information and product ion spectra of the glycosyl compounds. The most prominent fragment was found to arise from the aglycone ion, which provides molecular mass information about the glycosyl substituent and the aglycone. Product-ion spectra of the aglycone verified the identity by comparison with product-ion spectra of authentic standards. Methoxylated flavonoids provide characteristic fragmentation, i.e., loss of *CH3, which add to the usefulness of the method for identifying unknown flavonoids. Negative-mode APCI-MS is thus demonstrated to be a good alternative to the commonly employed positive mode operation. PMID- 11192170 TI - Separation ability and stoichiometry of cyclodextrin complexes. AB - Gas-liquid chromatography has been applied to search relations between selectivity towards isomers and stoichiometry of cyclodextrin complexes. The model tested compounds were: dimethylnaphthalenes and alpha- and beta-pinenes as constitutional isomers; cis/trans decalins, anetholes and isosafroles as diastereomers and as enantiomers (+/-)-alpha-pinenes and (+/-)-camphenes. Experimental retention data are used to confirm a simple theoretical model that allows distinguishing formation of G x CD complexes (1:1) and G x CD2 complexes (1:2). Based on the experimental data, stability constants K were evaluated. It has been found that remarkable selectivity factor alpha may appear both within the range of 1:1 stoichiometry (beta-CD complexes of decalins and of alpha- and beta-pinenes) and 1:2 stoichiometry (alpha-CD complexes with (+/-)-alpha-pinenes and (+/-)-camphenes). Occasionally selectivity arises from a different composition, when one isomer forms a 1:1 stoichiometry complex while another forms a 1:2 complex (dimethylnaphthalenes, cis/trans-anetholes and cis/trans isosafroles). PMID- 11192171 TI - Determination of floral fragrances of Rosa hybrida using solid-phase trapping solvent extraction and gas chromatography-mass spectrometry. AB - Floral fragrances emanated from Rosa hybrida were determined by solid-phase trapping extraction and GC-MS. A novel protocol of sampling technique was established. There is a variation in the recoveries depending on the adsorbent and components. A total of 41 compounds were identified in the floral fragrances of Rosa hybrida. These include alcohols, aldehydes, alkanes, monoterpenes, sesquiterpene, esters, ether and ketones. Citral, n-nonane, n-butyl acetate, n decane, beta-phenylethyl acetate and hexadecanol were major components. Floral fragrances differ between rose species and sample to sample within a single species. Interestingly, endocrine disruptors such as bis(2-ethylhexyl) phthalate were detected simultaneously. PMID- 11192172 TI - Simple cryoconcentration technique for the determination of peroxyacyl and alkyl nitrates in the atmosphere. AB - A gaseous mixture of methyl nitrate, n-propyl nitrate, peroxyacetyl nitrate and peroxypropionyl nitrate was successfully cryoconcentrated using a gas sampling valve with its loop filled with glass beads placed inside the GC oven which was cooled at -50 degrees C. The technique offered linearity over a ten fold concentration variation and sample volume range of 1-280 ml. The detection limit for 150 ml sample varied from 0.02-10 pptv depending on the compound. PMID- 11192173 TI - Solvating gas chromatography with chemiluminescence detection of nitroglycerine and other explosives. AB - A separation technique known as solvating gas chromatography (SGC), which utilizes packed capillary columns and neat carbon dioxide as mobile phase, was used for the separation of nitroglycerine (NG) and other nitrogen-containing explosives including 2,6-dinitrotoluene (2,6-DNT), 2,4-dinitrotolulene (2,4-DNT), 2,4,6-trinitrotoluene (2,4,6-TNT), and pentaerythritol tetranitrate (PETN). SGC was coupled for the first time to a selective chemiluminescence thermal energy analyzer (TEA) detector for nitro-functional group specificity and sensitive detection of these compounds. TEA calibration curve for NG showed linearity in the sub-microg ml(-1) range. Soil samples containing NG were used to test the validity of the technique. Detector response of SGC-TEA versus SGC-flame ionization detection for NG was also evaluated. PMID- 11192174 TI - Hindered amine stabilizers investigated by the use of packed capillary temperature programmed liquid chromatography. II: Poly-(N-beta-hydroxyethyl 2,2,6,6-tetramethyl-4-hydroxypiperidyl succinate). AB - Three different trademark products of a hindered amine stabilizer with the IUPAC name poly-(N-beta-hydroxyethyl-2,2,6,6-tetramethyl-4-hydroxypiperidyl succinate), have been analyzed and compared to each other by the use of packed capillary temperature programmed liquid chromatography and light scattering detection. The analysis by this method has shown that the products contained approximately 50 different homologues and/or other components. The method also demonstrated its potential in purity control of products from different manufacturers. PMID- 11192175 TI - Potential artifact formation of dioxins in ball clay during supercritical fluid extraction. AB - Earlier surveys indicate that meat, fish and dairy products are the principal source of polychlorinated dibenzo-p-dioxin (PCDD) exposure in the diet. A recent finding by others of PCDDs in chickens that consumed a feed containing PCDD led to the finding of ball clay, an anti-caking agent, as the source. Supercritical fluid extraction (SFE) was studied as a means to isolate PCDDs from commercial ball clays using GC-electron capture detection (muECD) as a means to screen for these contaminants. The finding of ng/g amounts and recoveries >100% in several samples of ball clay containing octachlorodibenzo-p-dioxin (OCDD) suggested that PCDD may form artifactually as a result of analysis. Studies on pentachlorophenol (PCP) fortified ball clay were carried out by SFE and soxhlet extraction and the results compared. The values obtained by SFE were considered more problematic. The results obtained from ball clay suggest that precautions need to be exercised when using SFE to analyze for dioxins in solid samples containing chlorophenols. PMID- 11192176 TI - Separation of amino acids by ion mobility spectrometry. AB - The mobilities of the 20 common amino acids were determined by electrospray ionization ion mobility spectrometry. It was found that each amino acid had a different drift time and hence a different reduced mobility constant K0. This difference in drift time was less than 0.1 ms in many cases. With the instrument used in this study it would not be possible to resolve mixtures of some of the amino acids. It would however be possible to determine any single amino acid. In addition, the detection limits were determined for the 20 amino acids. They ranged from 50 to 700 pg. This indicates that the detection limits were less than 3 pmol for all of the amino acids and that many amino acids had detection limits less than 1 pmol. PMID- 11192177 TI - Short synchronization system for estrus cycles in dairy heifers: a preliminary report. AB - In previous studies we demonstrated that the administration of a luteolytic dose of cloprostenol to dairy cows in luteal phase, followed by hCG plus estradiol benzoate (EB) 12 h later, led to successful timed AI 48 h after the initiation of treatment. This article reports two consecutive studies. In Study 1 we determined the pregnancy rate of dairy heifers in luteal phase (established by palpation per rectum) treated with cloprostenol followed by 250 IU of hCG plus 1 mg of EB 12 h later, and inseminated 48 h after cloprostenol injection. Study 2 was designed to evaluate the efficiency this synchronization protocol, irrespective of the estrus stage of the animals. In Study 1, 1272 Friesian heifers aged 14 to 16 months with a palpable corpus luteum received 500 mcg cloprostenol. Heifers were then synchronized either according to the hCG plus EB protocol (hCG-EB, n=637), or by a second dose of cloprostenol 11 d later (PG, n=636). Animals in this last group served as controls and were inseminated 72 and 96 h after the second cloprostenol injection. The pregnancy rate was significantly higher (P<0.0001) in the hCG-EB group (59.5%, 379/637) than in PG (44.8%, 285/636). In Study 2, 135 contemporary heifers (with no corresponding information on estrus stage) were subjected to the same protocol as those in the hCG-EB group of Study 1. These animals were classified in retrospect according to estrus stage established by plasma progesterone concentration. Pregnancy rates were 66.7% (24/36), 51% (25/49) and 58% (29/50) for animals in the follicular, early/late luteal, and mid-luteal phase, respectively. The total pregnancy rate was 57.8% (78/135). These findings indicate an improved pregnancy rate for heifers subjected to single insemination after cloprostenol/hCG/EB synchronization, compared to double insemination after synchronization by 2 cloprostenol injections 11 d apart. The cloprostenol/hCG/EB protocol did result in acceptable pregnancy rates after timed AI of dairy heifers regardless of their estrus cycle phase. PMID- 11192178 TI - Follicular and hormonal response to experimental suppression of FSH during follicle deviation in cattle. AB - A near steroid-free fraction of bovine follicular fluid was used to suppress FSH concentrations at the expected time of follicle deviation or when the largest follicle of Wave 1 reached > or = 8.0 mm (actual mean diameter, 8.4 mm; Hour 0). It was hypothesized that the low concentrations of FSH associated with deviation are inadequate for the smaller follicles but are needed for continued growth of the largest follicle. Control heifers (n=8) received 10 mL of saline, and treated heifers (n=16) received either 8.8 mL or 13.3 mL of the follicular-fluid fraction at Hours 0, 12, and 24. Between Hours -48 and 0, FSH concentrations decreased (P<0.05) and diameters of the 4 largest follicles increased (Hour effect, P<0.0001) similarly between groups. Concentrations of LH in the controls increased (P<0.05) between Hours -24 and -12 and decreased (P<0.05) between Hours 8 and 36, demonstrating a transient LH surge encompassing the expected beginning of deviation. In the treated group, a comparable increase in LH occurred before deviation but a decrease did not occur until after Hour 48. By Hour 4.5, the FSH concentrations in the treated group decreased (P<0.05) to below the concentrations in the controls. Suppressed diameter (P<0.001) of the largest follicle was detected at the first post-treatment examination (Hour 12; 7.5 h after FSH suppression) and was accompanied by reduced (P<0.04) systemic estradiol concentrations. The mean growth rates of the 3 smaller follicles in both the treated and control groups began to decrease at Hours -12 to 24 and were not different between groups during Hours 0 to 36. Concentrations of FSH in the treated group returned to control concentrations by Hour 24 (hour of last treatment). A rebound (P<0.05) in concentrations of FSH to >100% above control concentrations occurred by Hour 48 and was accompanied by resumed growth of the largest follicle in 75% of the heifers between Hours 48 and 72. The results demonstrated that the low concentrations of FSH associated with deviation can be further reduced by treatment with a nonsteroidal factor of follicular origin. Transient reduction of FSH concentrations to below the already low control concentrations inhibited the largest follicle but did not further inhibit the smaller follicles. These results support the hypothesis that the low FSH concentrations associated with follicle deviation are below the minimal requirements of the smaller or subordinate follicles but are needed for continued growth of the largest or dominant follicle in cattle. PMID- 11192179 TI - High-density ovine endometrial cells exhibit natural killer activity during early pregnancy. AB - Natural killer (NK)-like activity was assessed for peripheral blood lymphocytes (PBL) and unfractionated and fractionated endometrial cells recovered from ewes during the estrus cycle (Days 12 to 14) and early pregnancy (Days 16 to 18). The PBL and endometrial cells (each designated as effector cells) were cocultured with chromium-51 (51Cr) labeled NK-sensitive K-562 target cells in effector:target cell ratios ranging from 25:1 to 200:1, respectively. Lytic activity (i.e., release of 51Cr into the medium) was assessed at 22 h of culture. A high-density (> or = 1.088 g/mL) population of endometrial cells from the pregnant ewes exhibited NK-like activity, whereas endometrial cells from the cyclic ewes failed to exhibit activity. Lytic activity of these cells was greater (P < 0.05) for pregnant than for cyclic ewes (12.0 and 2.1%, respectively) at the effector:target cell ratio of 100:1, respectively. For both groups of ewes, PBL exhibited NK-like activity. These data indicate that the ovine endometrium contains NK-like cells with lytic activity between Days 16 and 18 of pregnancy. PMID- 11192180 TI - Assessment of stallion spermatozoa viability by flow cytometry and light microscope analysis. AB - Viability of spermatozoa can be assessed by numerous methods, but many are slow and poorly repeatable, and subjectively assess only 100 to 200 spermatozoa per ejaculate. We collected two ejaculates from each of 4 stallions, and extended them to 50x10(6) sperm/mL in a nonfat dried milk solids glucose extender (EZ Mixin). Half the ejaculate was freeze-killed by immersing in liquid nitrogen for 10 min. Aliquots using appropriate volumes of live and freeze-killed spermatozoa provided the following ratios of live:dead spermatozoa: 100:0, 75:25, 50:50, 25:75, 0:100. We determined the viability of each aliquot by 1) motility; 2) eosin-nigrosin staining; and 3) dual fluorescent staining. For the latter, aliquots incubated with SYBR-14 and propidium iodide had live and dead spermatozoa quantitated by fluorescent microscope (2 x 100 sperm/sample) and flow cytometry (10,000 sperm/sample). We found a linear relationship between the ratio of live:dead spermatozoa and the percentage of spermatozoa counted as live (P<0.0001). For fresh spermatozoa, correlation coefficients of the known live:dead ratio were high for all methods (eosin-nigrosin, r>0.75; fluorescent microscope, r>0.76; flow cytometry, r>0.75; motility, r>0.76). To determine viability of cryopreserved equine spermatozoa, we froze 17 fresh ejaculates from 6 stallions in a glycine extender. Each sample was thawed, extended 1:1 with EZ Mixin and evaluated as above. Cryopreserved spermatozoa assessed by flow cytometry tended to be less well correlated (r<0.68) with the other methods, and estimates were significantly higher with eosin-nigrosin staining (P<0.001). This study shows that different methods may equally estimate viability of fresh equine spermatozoa. However, evaluation by flow cytometry appears to be less precise with cryopreserved spermatozoa. PMID- 11192181 TI - Growth hormone gene polymorphisms and growth performance traits in Duroc, Landrace and Tao-Yuan pigs. AB - This study investigated the restriction fragment length polymorphism (RFLP) of the porcine growth hormone (pGH) gene in Duroc, Landrace, and Tao-Yuan pigs and its effects on growth performance and levels of plasma growth hormone in peripheral circulation. Genomic DNA extracted from 81 Tao-Yuan, 60 Landrace and 48 Duroc pigs were subjected to Southern blot hybridization with a pGH cDNA probe. Polymorphism was detected with the restriction enzymes TaqI and DraI. A comparison of these three breeds showed significant differences in allelic frequencies. Blood samples for radioimmunoassay (RIA) of GH were collected biweekly during the experimental period from pigs 12 to 40 weeks of age. Tao-Yuan pigs showed a mean plasma GH level (2.51 +/- 1.23 ng/mL) that was much lower than that of the Landrace (3.80 +/- 1.52 ng/mL) and Duroc (4.20 +/- 1.03 ng/mL) pigs (P < 0.05). Moreover, the Tao-Yuan pigs also showed poorer growth performance than the Landrace and the Duroc pigs both in the daily weight gain (0.37 +/- 0.06 vs. 0.67 +/- 0.05 and 0.70 +/- 0.05 kg/day, P < 0.01) and feed efficiency (3.12 +/- 0.28 vs. 2.60 +/- 0.14 and 2.52 +/- 0.12, P < 0.05). These results suggest that the growth performance trait in these pigs is highly correlated with their growth hormone genotype. PMID- 11192182 TI - Development of bovine embryos on Vero/BRL cell monolayers (mixed co-culture). AB - The objective of this study was to test a new co-culture system of bovine embryos, which we call "mixed co-culture." This system consists of culturing embryos on cell monolayers composed of both Vero and BRL cells (Vero/BRL). Cumulus-oocyte complexes from ovaries of slaughtered cows were matured and fertilized in vitro. The presumptive zygotes were cultured with Vero/BRL (Group 1), BRL (Group 2) or Vero (Group 3) cell monolayers, in 40 microL drops of Menezo B2 medium supplemented with 10% FBS and antibiotics. The development of the presumptive zygotes was compared on Day 2 [48 h post insemination (pi)] and Day 7 (168 h pi). On Day 2, there was no difference between the groups. On Day 7, the highest percentage of compacted morulae/blastocysts was observed in mixed co culture of Vero/BRL cells: 40% versus 36% on BRL versus 27% on Vero cell monolayers. The differences were statistically significant (P < or = 0.05). Among compacted morulae/blastocysts, blastocysts prevailed in mixed co-culture: 67% on Vero/BRL as compared with 55% on BRL and 27% on Vero cell monolayers. The differences were highly statistically significant (P < or = 0.01). The results suggest that Vero/BRL cells improve the development of bovine embryos. PMID- 11192183 TI - Relationship between heparin binding to spermatozoa and the fertility of dairy bulls. AB - The presence of heparin in in vitro media has been implicated in improved fertility parameters of bull spermatozoa. In a previous study, Zhang et al. (25) obtained an estimate of bull nonreturn rates based on spermatozoal concentration, motility and zona pellucida binding (24). The objective of this study was to test for a relationship between fertility parameters previously estimated for the same batch of cryopreserved semen (25) and amount of heparin bound to spermatozoa. 3H heparin binding to spermatozoa was assessed by radioimmunoassay, and statistical correlations were drawn to previously measured sperm characteristics. Preliminary experiments established optimal binding conditions of 25 degrees C, and 60 min incubation with 3H-heparin at a concentration of 50,000 cpm. 3H-heparin bound to an average of 2.2 x 10(6) receptors/cell with a Kd of 2.0 x 10(-7) M. The total 3H-heparin bound to spermatozoa from different bulls was significantly different (P<0.003). However, the total 3H-heparin bound to spermatozoa was not correlated with any measured sperm parameter, including zona pellucida binding, embryo cleavage and blastocyst formation, and 56-day nonreturn rates (P>0.19). Thus, the total amount of heparin bound to the surface of spermatozoa may not be relevant to fertilizing ability. PMID- 11192184 TI - A novel approach for in vitro production of bovine embryos: use of the Oxoid atmosphere generating system. AB - The importance of the incubator type is often overlooked when protocols for in vitro production of embryos are evaluated. In this study the ability of a standard CO2 Heraeus incubator and the Oxoid CO2Gen atmosphere-generating system to support bovine in vitro oocyte maturation, fertilization and embryo development is described for the first time. The Oxoid CO2Gen gas generating system, originally designed for the growth of bacteria, is based on the chemical reaction of ascorbic acid and air. When the sachet with ascorbic acid is placed in the confined volume of the airtight AnaeroJar, an atmosphere of 6% CO2 in 15% O2 is created, which is comparable to the 5% CO2 and 20% O2 used for standard in vitro production of bovine embryos. In the first set of experiments oocyte in vitro maturation (IVM), fertilization (IVF) and embryo culture (IVC) were allocated to one or the other of the culture systems. In the second set of experiments IVM and IVF took place in the Heraeus incubator, while IVC was allocated either to the Heraeus or to the AnaeroJar. During experiments the AnaeroJar was placed in the Heraeus incubator to ensure identical incubation temperatures of 38.8 degrees C. A standard protocol was used for production of embryos: 23 h of IVM in TCM-199, 20 h of IVF with frozen-thawed washed spermatozoa in TALP medium and 7 days of IVC (8 days after insemination) in B2 medium with bovine oviduct epithelial cells. In the first set of experiments, based on a total of 766 inseminated oocytes, the Day 8 blastocyst rates were the same in the Heraeus incubator and the AnaeroJar: 30% vs. 30% with oviduct cell coculture, and 21% vs. 18% without coculture. In the second set of experiments, based on 1963 inseminated oocytes, the average blastocyst rates were 27% vs. 32% from the Heraeus incubator and the AnaeroJar. In 2 of 6 replicates blastocyst rates were lower in the Heraeus incubator than in the jar; in the remaining replicates they were alike. No differences were noted in blastocyst kinetics or morphology. In conclusion, the Oxoid gas generating system seems to be a cheap, convenient and stable alternative to expensive CO2 incubators, not only for the growth of bacteria, but also for in vitro production of bovine embryos. PMID- 11192185 TI - Transvaginal collection and ultrastructure of llama (Lama glama) oocytes. AB - Ultrasound-guided transvaginal follicle aspiration has been described as a noninvasive and repeatable procedure for oocyte collection in several species, but its use has not been described for any of the members of the family, Camelidae. A study was designed to determine the feasibility of an ultrasound guided transvaginal approach for oocyte collection in llamas. Fifteen non pregnant, adult female llamas (10 non-stimulated and 5 superstimulated) were examined by transrectal ultrasonography with a 7.5-MHz linear-array transducer to determine the number and diameter of follicles available for aspiration. After caudal epidural anesthesia was induced, the 7.5-MHz linear-array transducer was fastened to a long rigid handle and inserted intravaginally. The free hand was placed into the rectum to manipulate the ovaries, one at a time, in position against the vaginal wall over the face of the transducer. A 20-gauge, 55-cm-long, single-lumen needle was advanced through the vaginal fornix and into follicles > or = 3 mm in diameter. Follicular contents were aspirated using a regulated vacuum pump (flow rate = 33 mL/min; approximately 150 mm Hg) into a tube containing 3 mL of phosphate buffered saline and 0.2% BSA. Fluid was filtered (75 microm mesh), and oocytes were located and morphologically evaluated using a stereomicroscope. Overall, 134 follicles were aspirated, and 76 oocytes were collected (collection rate = 57%). Thirty-two oocytes (42%) were surrounded by multiple layers of compacted granulosa cells and had homogenous dark ooplasm; 13 oocytes (17%) were surrounded by the corona radiata layer only and had heavily granulated ooplasm; 9 oocytes (12%) were denuded and had homogenous dark ooplasm; and 22 oocytes (29%) were denuded and displayed signs of ooplasm degeneration. The ultrastructure of llama oocytes was similar to that of cattle except for conspicuous accumulation of large lipid droplets in the cytoplasm. Twenty-four hours after follicle aspiration, the ovaries were examined by transrectal ultrasonography and intrafollicular hematomas were detected in 3 llamas (9 of 48 follicles aspirated). Results demonstrate the potential utility of a transvaginal ultrasound-guided technique for oocyte collection and in vitro embryo production in llamas. Oocytes of llamas bear an ultrustructural resemblance to those of cattle, but are distinguished by a predominance of cytoplasmic lipid. PMID- 11192186 TI - Mummification of fetal membranes in the bovine vagina: a case report. AB - Papyraceous, mummified fetal membranes were found in the vagina of a cow at the end of the fourth month after a normal delivery. The uterus and cervix were without any pathological changes. The cow conceived on Day 36 after removal of the mummified fetal membranes upon the second insemination. Apart from the uncommon nature of the case, it proves that after calving the bovine vagina can maintain a sterile environment and that the constrictive mechanism of the vagina can be strong enough to hinder for a long time the discharge of fetal membranes and access of microbes to the vagina. PMID- 11192187 TI - Treatments resulting in pregnancy in nonovulating, hormone-treated oocyte recipient mares. AB - Synchronization of follicle growth between oocyte donor and recipient mares is difficult. To avoid this, recipient mares in a clinical program were used during a period of low follicular activity, and were treated with estrogen before transfer and progesterone after transfer. Five pregnancies were established after oocyte transfer to nonovulating, hormone-treated recipient mares. One pregnancy was lost before 30 d gestation, and the other 4 foals were carried to term. One foal died at birth. Establishment and maintenance of pregnancy in these mares indicates that nonovulating, hormone-treated mares may offer an alternative to cyclic recipients in oocyte transfer programs. PMID- 11192188 TI - Effect of boar contact on follicular development and on estrus expression after weaning in primiparous sows. AB - Boar contact can induce ovarian activity, advance estrus and stimulate estrous behavior in sows. High amounts of boar contact can, however, suppress estrous behaviour. The present study with primiparous sows was designed to compare sows that had contact with a teaser boar during detection of estrus, with sows that had no boar contact at all. Number of sows detected in estrus within 9 d after weaning, onset and duration of estrus, follicular dynamics and timing of ovulation were studied. Boar contact increased the number of sows that ovulated and showed estrus from 14 of 47 to 24 of 47 (P < 0.05). Average timing of ovulation was later for sows with boar contact (165 h vs 150 h after weaning). Duration of estrus, detected without a boar, was similar in the two groups. For the sows with boar contact, duration of estrus detected with a boar was longer than estrus detected without a boar (56 vs 38 h; P < .01). Follicular dynamics were not affected by boar contact; boar contact only increased the number of sows with ovulation. Ovulatory sows showed a larger increase in follicular diameter (P < 0.01) from weaning to Day 4 after weaning (from 2.3 to 5.4 mm) than anovulatory sows (from 2.5 to 4 mm). Anovulatory sows did not show follicular growth after Day 4. It is concluded that boar contact can increase the number of sows that ovulate and show estrus after weaning. Estrous behavior does not seem to be suppressed by contact with a teaser boar, compared to sows without boar contact. PMID- 11192189 TI - Postovulatory effect of repeated intravenous administration of ACTH on the contractile activity of the oviduct, ova transport and endocrine status of recently ovulated and unrestrained sows. AB - The effect of repeated intravenous administration of ACTH (Synacthen depot) on the contractile activity of the oviduct, ova transport and endocrine status was studied in 11 Swedish crossbred (Landrace x Yorkshire) multiparous sows. In the second estrus after weaning, the ACTH group (Group A, n=6) sows were administered 0.01 mg/kg body weight of ACTH every 6 h commencing 4 to 8 h after ovulation, whereas the control group (Group C, n=5) sows were administered saline solution. Immediately after standing estrus, a Millar pressure transducer was placed about 3 cm into the isthmus via a laparotomy. Blood samples for hormonal analyses and pressure recordings of the oviduct were collected from all sows until slaughter. After slaughter, the genital tract opposite to the side with the transducer was retrieved, and 3 equal isthmic segments and the first third of the uterine horn portion adjacent to the UTJ were flushed separately for ova recovery. Cortisol levels were significantly (P<0.05) elevated after ACTH administration. Progesterone and PGF2alpha metabolite levels were significantly (P<0.05) elevated only after the first ACTH administration. No significant differences (P>0.05) were seen in the mean pressure and frequencies of phasic pressure fluctuations either before or after every ACTH administration between Groups A and C. No significant difference (P>0.05) was seen in the proportion of ova recovered in the different segments between Groups A and C. It can be concluded from the present study that the administration of ACTH (0.01 mg/kg body weight) to sows at 4 to 8 h after ovulation, and after each subsequent ACTH administration, elevates cortisol levels, whereas progesterone and PGF2alpha metabolite levels are elevated only after the first treatment, and that this has no effect on the mean isthmic pressure, the frequency of phasic pressure fluctuations or ova transport. PMID- 11192190 TI - A meta-analysis of studies of the effect of GnRH 11-14 days after insemination on pregnancy rates in cattle. AB - A number of studies have used GnRH between 11 and 14 days after insemination to improve pregnancy rates in cows, however published results have not been consistent. We wished to investigate whether a consolidated estimate of the response could be quantified. Therefore we conducted a meta-analysis of the available data, 19 studies from 14 published papers, on the effect of GnRH analogs on pregnancy rate when given between Days 11 and 14 after first insemination. Odds ratios (the relative probability of pregnancy between treated and control cows) were compared for each study and found to vary significantly among studies, ranging from 0 to 22%. We showed by logistic regression analysis that response to GnRH treatment varied with cow type (beef or dairy), age (cow or heifer), estrus synchronization (synchronized or natural), pregnancy diagnosis (method and time) and effect of individual study. When all these variables were included only 6 of 14 publications could be analyzed, representing 2,541 instead of 10,945 cows. In this limited subgroup of data, a significant improvement in pregnancy rate was detected among treated cattle (odds ratio = 1.33; P<0.01). PMID- 11192192 TI - [Preimplantation genetic diagnosis, finally a reality in France]. PMID- 11192191 TI - A combination of EGF and IGF-I accelerates the progression of meiosis in bovine follicular oocytes in vitro and fetal calf serum neutralizes the acceleration effect. AB - The effects of a combination of EGF and IGF-I (GFs) on the progress of meiosis and on their developmental competence were examined in cumulus-enclosed bovine oocytes. Exposure to GFs in serum-free, 0.3% PVP-containing maturation medium significantly (P<0.05) increased the frequency of oocytes with the first polar body (PB) at 16 h of culture and decreased those with PB at 20 h. The cleavage rates of PB-extruded oocytes after fertilization were not affected by treatment of GFs during maturation culture, and blastocyst yield was not improved by GFs treatment. Although replacement of PVP from GFs-containing medium with fatty acid free BSA did not affect the timing of PB extrusion, replacement with 10% FCS neutralized the acceleration effects of GFs. Replacement for macromolecule in maturation medium did not improve blastocyst yield of PB-extruded oocytes after fertilization. These results indicate that the progression of meiosis in bovine oocytes with cumulus cells is accelerated by exposure to GFs in serum-free maturation medium but their developmental competence is not improved, and that the acceleration effects on the progress of meiosis is neutralized by the presence of FCS in maturation medium with no improvement of developmental competence after in vitro fertilization. PMID- 11192193 TI - [Evaluation of thomboembolic risk before ovarian stimulation: what balance? What prevention?]. AB - The pathophysiology of thrombotic events remains unclear among women undergoing ovulation induction. In this review, present knowledge is summarized from the literature. Prospective studies are needed to determine risk factors and therapeutic approach of these thrombotic complications. PMID- 11192194 TI - [Major vascular complications from gynecologic laparoscopy]. AB - OBJECTIVE: To specify the circumstances of occurence, the means of diagnosis, the risk factors and the means of prevention for major vascular injuries (MVI) during gynecologic laparoscopic procedure. STUDY DESIGN: Retrospective case review study of 24 patients. RESULTS: Twenty-four patients with 31 MVI were identified. The average age of the patients was 32.8 +/- 10.6 years and the mean body index mass was 22.4 +/- 4.0 kg/m2. Three of four of the MVI occurred during the setting-up phase of laparoscopy (19 cases; 79.2%). In five cases (20.8%) MVI occurred during the laparoscopic surgical procedure. Fifteen of the MVI occurring during the set up phase were secondary to insertion of the umbilical trocar and four to insertion of the needle used to create the pneumoperitoneum. A minimum of six MVI secondary to insertion of the umbilical trocar were observed with disposable trocars. In every case diagnosis was performed during the laparoscopic procedure. Five patients (20.8%) died and three others (12.5%) presented serious complications (phlebitis (one case); ischemia (two cases) with a reoperation for one patient). CONCLUSION: MVI are rare but serious complications of gynecologic laparoscopy. Prevention relies on the surgeon's experience and strict respect of the safety rules. In the vast majority of cases, it is necessary to convert to laparotomy immediately, calling in a vascular surgeon. PMID- 11192195 TI - [Non-palpable breast lesions: radio-pathologic correlations on open excisional biopsies. Significance of the choice of technique for minimal excisional biopsy]. AB - OBJECTIVE: To decrease the number of open excisional breast biopsies, percutaneous breast biopsies have been developed to perform the histologic diagnosis of non-palpable breast lesions. Some techniques allow a complete removal of small radiologic lesions. To evaluate the accuracy of a pathologic analysis performed only on the radiologic findings, we studied the radiologic and histologic correlation on open excisional biopsy (OEB) specimens. The aim of our study was to determine how many carcinomas were found distant from the radiologic findings. MATERIAL AND METHODS: Non-palpable breast lesions have been excised after preoperative localization. The radiologic findings were classified in microcalcifications, masses, architectural distortion and in sonographic masses. The correlation between the radiologic and pathologic findings was studied and all the lesions incidentally discovered on histology with no correlation with the imaging findings or distant from the radiologic findings were described. One hundred and twenty-nine lesions have been evaluated in 99 patients. Radiologic findings included 79 clusters of microcalcifications, 30 masses, six architectural distortions and 14 sonographic lesions. RESULTS: The histopathological results were benign in 41.9%, malignant in 49.6% and atypical hyperplasia lesions were discovered in 8.5%. All benign lesions were correlated to radiologic findings. No malignant lesion was found at a distance. In three cases atypical hyperplasia lesions were coexistent with the radiologic findings correlated with benign lesions and in three cases they were found at a distance. All but two malignant lesions were correlated with radiologic findings. In two cases a microinvasive carcinoma and foci of labular carcinoma in situ were found coexistent with benign lesions. The subgroup of small lesions lesser than 10 mm included 31 benign lesions. A complete removal of these lesions should be obtained with percutaneous biopsies. CONCLUSION: A pathologic analysis targeted on radiologic findings is accurate. Numerous open excisional biopsies performed for benign pathology should be avoided. PMID- 11192196 TI - [Morphological aspect of embryos obtained after fertilization in vitro for male factor or ICSI]. AB - OBJECTIVE: In order to study the eventual impact on fertilization and embryo characteristics of the microinjection procedure we compared the quality of the embryos obtained by ICSI with those of in vitro fertilization with male factors (MF IVF). MATERIAL AND METHODS: One hundred thirty-four cycles of IVF treatment (group 1) were selected with oligoasthenozoospermia according to WHO criteria with a total number of motile spermatozoa between 500,000 and 1 million. One thousand eighty-eight mature oocytes and 486 embryos were obtained. One hundred forty-three cycles of intracytoplasmic sperm injection (group 2) were performed in couples whose in vitro fertilization was imparticable because of extreme sperm impairment. One thousand one hundred forty-seven mature oocytes were injected and 626 embryos were obtained. RESULTS: In group 1, the pregnancy rate per embryo transfer and the implantation rate were respectively 22.7% and 12.3%. In group 2, the pregnancy rate per embryo transfer was 37.1% and the implantation rate was 17%. The statistical analysis of the embryos obtained in the two different groups did not demonstrate any difference in the distribution of the more regular and less fragmented embryos (group A) and those of the more irregular and fragmented embryos (group B). No statistical difference was demonstrated in the chronology of the division of these embryos (groups 1 and 2). CONCLUSION: The pregnancy rate by cycle and by transfer reported by ICSI (p < 0.003 and p < 0.015 respectively) could be related to a significantly higher mean number of transferred embryos (2.65 vs 2.02) in probable relation with a higher cleavage rate (p < 0.00001). PMID- 11192197 TI - [The experience of menstruation and its disorders in 603 women using contraception in 1999]. AB - AIM: An epidemiological survey completed during the first quarter of 1999 assesses the frequency of menstrual disorders as well as their effects on the lives of women using contraception. MATERIALS AND METHODS: The results presented involve a sample of 603 women, with 405 using the pill and 198 fitted with an IUD. The average age of onset of menstruation in the sampled population was 12.8 years. Although most women declared that they felt no anxiety at the time, over one-third of the women surveyed explained that they felt a certain hesitancy in discussing the topic. Even today, certain feelings, such as shame or pride, are still evoked in the interviews. Although over half believe that it is normal to menstruate, the process is nevertheless considered "somewhat bothersome" by certain women who also refer to "purification." Traditional cultural perspectives remain a strong influence. Menstrual disorders predating the initial use of contraception were reported in 150 women (occasional intermenstrual bleeding, 130 cases; other anomalies excluding metrorrhagia, 27 cases). Even if most of the women believe these problems to be inevitable, they also claim to be relatively troubled by these disorders, which often involve a considerable degree of discomfort. Such disorders are significantly more frequent in the "IUD" group, as well as in women who claim a very early onset of menstruation and those who consider explanations provided by the physician as "insufficient." CONCLUSION: The difference creates a certain fear with respect to any social or individual norm that may have been internalized. Thus the information presented in this study may provide ways and means to better understand women in general and our women patients in particular. PMID- 11192198 TI - [Pathology of gestational trophoblastic tumors]. AB - Gestational trophoblastic tumours result from an abnormal proliferation of different types of trophoblasts. The morphological pattern, together with the immunohistochemical aspect, the cytogenetic data and the clinical profile, helps identify each pathological entity. Hydatiform moles represent malformed placentas caused by genetic aberrations of the villous trophoblast. A complete hydatiform mole displays an hydropic degeneration of all the chorionic villi with a more or less marked proliferation of trophoblasts. A partial hydatiform mole is made up of molar vesicles interspersed with normal chorionic villi. In an invasive hydatiform mole or chorioma destruens, molar vesicles penetrate the myometrium giving rise to a mass distorting the uterine wall. A choriocarcinoma is a malignant proliferation of atypical villous trophoblasts without villi formation. Necrosis, haemorrhage, vascular invasion and distant metastases strongly compromise its outcome. A trophoblastic implantation site tumor, clearly less frequent, results from a proliferation of extravillous trophoblasts, particular for their secretion of human placental lactogen hormone (hPL). This tumour, exceptionally malignant, should be differentiated from the exaggerated placental site and its variants. Except for the placental site trophoblastic tumour, and whatever the outcome (benign or malignant), all gestational trophoblastic tumours secrete the beta-subunit of the chorionic gonadotropic hormone (beta-hCG) more or less abundantly. The serum or urinary level of this unit is proportional to the tumour volume and represents a fundamental basis for the follow-up of these tumours. Multidisciplinary care of high-risk cases allows us to cure the disease, and helps the patient recover her reproductive uterine function. PMID- 11192199 TI - [Response of the authors to the correspondence of B. Broussin]. PMID- 11192200 TI - [In response to the article by P. Martel et al. Use of CO2 laser in continuous or pulse mode for accomplishing conization: apropos of 230 cases. Gynecol Obstet Fertil 2000; 28: 536-46 ]. PMID- 11192201 TI - [In response to the article by E. Leblanc et al. The treatment of early stage cervical cancer with pelvic lymph node involvement. Gynecol Obstet Fertil 2000; 28: 518-25]. PMID- 11192202 TI - [In response to the article by M.C. Rojat-Habib et al. Usefulness of endocervical margin analysis of conization specimens. Gyneol Obstet Fertil 2000; 28: 518-25 ]. PMID- 11192203 TI - [The concept of selective action steroids]. PMID- 11192204 TI - [Measuring the risk of infection after premature rupture of the membranes: consideration of complemenatary examinations and biological markers?]. PMID- 11192205 TI - [Extemporaneous anatomopathological examinations in mammary and thyroid pathologies]. PMID- 11192206 TI - [Should colposcopy be systematically performed on all women presenting with cytologic anomalies?]. PMID- 11192207 TI - [Systematic colposcopy for generating overevaluations]. PMID- 11192208 TI - [The first World War and the explosion of venereal disease morbidity. III. The hunting for prostitutes: an impossible war?]. PMID- 11192209 TI - Suggestion of a cause-and-effect relationship among coal rank, airborne dust, and incidence of workers' pneumoconiosis. PMID- 11192210 TI - Identifying the determinants of viable microorganisms in the air and bulk metalworking fluids. AB - Exposure assessment was conducted for an epidemiologic study of the respiratory effects of exposure to metalworking fluids (MWF). As part of the study, airborne microorganisms were collected with a two-stage microbial impactor, and a sample of the bulk soluble MWF was collected from each machine sump, as well as information about the work environment. These data were then used to develop multivariate statistical models of the determinants bulk MWF and airborne microbial levels. Microbial concentrations in the bulk MWF ranged from 5 x 10(4) to 5 x 10(10) colony-forming units (CFU)/mL, with a geometric mean of 3.4 x 10(7) CFU/mL. The geometric mean airborne microbial level was 182 CFU/m3 (for particles size <8 microm) with a range of 1 to 8,308 CFU/m3. In modeling the determinants of bulk microorganisms, fluid-related factors were the most important characteristics associated with microbial levels, followed by process-related and environmental factors. The final full multivariate model predicted a significant reduction in bulk microbial levels by increasing pH of the fluid and reducing the amount of tramp oil leaking into the fluid. For the airborne microbial models, process-related factors were the major characteristics associated with microbial levels, followed by factors related to worker activities and environmental factors. The final full multivariate model predicted a significant control of airborne microorganisms by increasing worker distance from the machine, reducing the number of machines within 10 feet of the worker, decreasing the bulk microbial levels, and adding machine enclosures. These models can be used to prioritize nonbiocidal interventions to control microbial contamination of the bulk MWF and the air. PMID- 11192211 TI - Particle settling after lead-based paint abatement work and clearance waiting period. AB - This study investigated the evolution of airborne particle concentration and size distribution following abatement work in a controlled environment utilizing direct real-time particle monitoring and used it to project potential lead loadings as those particles settle. An 860 ft3 environmental test chamber with sophisticated ventilation and air purifying systems was built. Wooden doors with lead-based paint were dry sanded or scraped to generate the highest feasible airborne lead concentrations. Size-fractional airborne particle concentrations decreased exponentially with time in all tests, even with no air exchange, consistent with the stirred model of constantly mixed air, which predicts longer settling than for tranquil settling. Very low levels of air mixing generated by temperature gradients and initial room air turbulence affected particle settling. About 90% of airborne lead mass settled within 1 hour after active abatement, before final cleaning began. During the second waiting period of 1 hour, which followed cleaning of the floor, additional dust settled so that the additional potential lead loading from remaining airborne lead was less than 20 microg/ft2. For this worst case scenario, the underestimate of the lead loading done by the clearance sampling did not exceed about 30%. For more realistic conditions, the underestimates are projected to be much lower than the new 40 microg/ft2 Housing and Urban Development (HUD) clearance standards for floor dust lead. These results were obtained for the first waiting period (between the end of active abatement and the beginning of cleaning) of 1 hour, as recommended by HUD guidelines. Thus, this study demonstrates no need to increase either the first or second waiting period. PMID- 11192212 TI - A new passive sampler for regulated workplace ketones. AB - A new solid sorbent passive air sampler for ketones has a silicone membrane atop a diffusion cylindrical path length of 1.1 cm and diameter 1.3 cm above a pellet of Tenax TA coated with 10% (w/w) O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine hydrochloride. Vapors of known concentrations approximating their workplace permissible exposure limits of Occupational Safety and Health Administration regulated ketones at a relative humidity (RH) of 3 +/- 1% were generated by a syringe pump connected to a dynamic air dilution system connected to an exposure chamber that allowed measurement of face velocities, temperatures, exposing vapor concentrations, and RHs. The O-oxime derivative was desorbed with hexane, and an aliquot injected for gas chromatographic analysis on a nonpolar capillary column by mass spectrometric or electron capture detection. The experimental passive sampler sampling rates in milliliters per minute at 25 degrees C were 4.07 +/- 0.49, cyclohexanone; 6.30 +/- 0.59, diethyl ketone; 6.31 +/- 0.31, ethyl n-butyl ketone; 3.78 +/- 0.25, methyl n-amyl ketone; 3.43 +/- 0.19, methyl n-butyl ketone; 6.48 +/- 0.64, methyl ethyl ketone; 4.37 +/- 0.43, methyl isopropyl ketone; and 4.57 +/- 0.17, methyl n-propyl ketone. These preliminary data show that sterically unhindered ketones can be sampled by the passive sampler as well as aldehydes. PMID- 11192213 TI - Lead exposure among workers renovating a previously deleaded bridge: comparison of trades, work tasks. AB - Airborne and surface lead exposures were evaluated for construction trade groups at a previously deleaded bridge renovation site in the midwestern United States. Although all lead-based paint should have been removed, old layers of leaded paint were still present on some sections of the bridge. Ironworkers performing metal torch cutting had the highest exposures (188 microg/m3), followed by workers engaged in clean-up operations and paint removal (p < 0.001). Respirators were most frequently worn by workers with the greatest lead exposures; however, laborers performing clean-up operations had exposures to lead dust of 43 microg/m3 and often wore no respiratory protection. Wipe samples revealed that almost all contractor vehicles were contaminated with lead. Heavy equipment operators with low airborne lead exposure had the highest levels of surface contamination in personal vehicles (3,600 microg/m2). Laborers cleaning structural steel with compressed air and ironworkers exposed to lead fumes from cutting had the highest concentrations of lead dust on clothing (mean 4,766 microg/m2). Handwashing facilities were provided, but were infrequently used. No separate clothes changing facility was available at the site. The potential for "take-home" contamination was high, even though this site was thought to be relatively free of lead. Construction contractors and their workers need to be aware that previous deleading of a site may not preclude exposure to significant amounts of lead. PMID- 11192214 TI - A method for the analysis of butyltin chlorides in air by gas chromatography with atomic emission detection. AB - An initial screening test compared the use of tropolone (2-hydroxy-2,4-6 cycloheptatrienone) in acetic acid with sodium diethyldithiocarbamate (NaDDC) as chelating agents for the extraction of butyltin chlorides from glass fiber filters and XAD-2 resin tube. NaDDC was chosen for subsequent analyses. Mono-, di , and tributyltin chloride were spiked onto glass fiber filters and XAD-2 resin, extracted in toluene with NaDDC and derivatized with pentylmagnesium bromide. Derivatized butyltin species were determined by gas chromatography with plasma atomic emission detection. Glass fiber filters and XAD-2 resin were found to provide high retention of butyltin compounds during sampling and efficient recovery of butyltin compounds by extraction with NaDDC. PMID- 11192215 TI - Lip lead as an alternative measure for lead exposure assessment of lead battery assembly workers. AB - This study investigated lead exposures of lead battery assembly workers in Taiwan. A special attempt was made to evaluate the use of lip lead as an alternative index for occupational lead exposure. Ninety-six of 113 workers from a lead battery plant were recruited as study subjects. Air lead; lead loadings on workers' sleeves, gloves, hands, cheeks, and lips; and blood lead were determined for exposure assessment. A questionnaire also was administered to collect information on work history, suspected exogenous lead sources, and personal behavior and activities. Geometric means of total air lead at different subareas ranged from 0.070 (2.5 geometric standard deviation [GSD]) to 0.159 (1.8 GSD) mg/m3. Geometric means of respirable air lead level for different subgroups of workers varied from 0.009 (2.0 GSD) to 0.032 (1.9 GSD) mg/m3, whereas those of the blood lead level ranged from 22.4 (1.3 GSD) to 44.5 (1.3 GSD) microg/dL. The heaviest lead loadings were found for plate-processing workers (e.g., 66.4 [1.5 GSD] on gloves, 0.80 [3.7 GSD] on cheeks, and 0.79 [3.2 GSD] microg/cm2) on bare hands after washing. Blood lead level was significantly correlated with lead levels in air, lead loadings on lips, and bare hands after washing (r=0.24-0.30). Results of multiple regression analysis showed that only lip lead had a significant effect on the blood lead, whereas respirable air lead and personal behavior had only mild effects in this model. It was concluded that lip lead level may be used as an alternative index of lead exposure to facilitate the estimation of lead uptake through ingestion. PMID- 11192216 TI - Copper exposure and metal fume fever: lack of evidence for a causal relationship. AB - A systematic search was made of the world literature concerned with possible adverse health effects of inhalation exposure to copper fume and dust. Seven reports published over the past 88 years were identified that contain original human data and purport to document that exposure to copper dust or fume caused metal fume fever (MFF) or an MFF-like syndrome. Insufficient evidence was found to conclude that exposures to copper dust and copper fume cause MFF. Limitations included absence of exposure measurements, atypical symptoms and complaints, and lack of consistency among types of work associated with symptoms. Given the extensive use of copper in many industries and operations, it is evident that if copper-induced MFF does occur, it is a rare event. PMID- 11192217 TI - A quantitative study of aromatic amine permeation through protective gloves using amine adsorptive pads. AB - A quantitative study of aromatic amine permeation through a glove material using Permea-Tec aromatic amine pads, used for the detection of chemical breakthrough of protective clothing, was performed for aniline following the microwave extraction process and gas chromatographic analysis. Aniline exhibited >99% adsorption on the pads at a spiking level of 1.94 mg (1.9 microL). Aniline showed recoveries from 65 to 89% (RSD < or =5.6%) over the range 1.1-1.9 microL (1.12 1.94 mg) of aniline applied to pads. The modified ASTM F739 and direct permeability testing procedures were used to determine breakthrough times for five protective glove materials using aniline as a challenge chemical. Breakthrough times for six protective gloves were determined, ranging from 182 sec to 82 min. The quantitative concentration of aniline on the pads following permeation through the gloves also was determined, ranging from 0.53 to 0.55 mg/cm2 (1.79-1.88 mg/pad). PMID- 11192218 TI - National Occupational Health Service policies and programs for workers in small scale industries in China. AB - Over the 14 years since economic reform began, and the restructuring of the economy to encourage international trade, a large number of township enterprises have been developed and put into operation in the Peoples Republic of China. From 1978 to 1991, the number of enterprises has increased 11.5 times; the number of employees has increased 2.4 times; the fixed assets have increased 13.7 times; and the value of the total output has increased 22.5 times. In this article, a report is given on a sample survey in 30 counties in 1990, which showed that 82.69% of rural industrial enterprises had at least one type of occupational hazard in their work environments. Workers engaged in at least one type of hazardous working environment accounted for 33.91% of the blue-collar workers. Physical examinations were performed for seven types of occupational diseases: silicosis, coal worker's pneumoconiosis, asbestosis, chronic lead poisoning, benzene analogs poisoning, chronic chromium poisoning, and noise-induced hearing loss. The total detectable rate of the seven types of occupational diseases was 4.4% among those workers. In addition, 11% had illnesses suspected of being (though not proven to be) caused by occupational exposures. Most township enterprises do not provide basic occupational health services. The coverage of five routine occupational health service activities provided for township enterprises were very limited, from 1.4 to 36%. PMID- 11192219 TI - Evaluation of portable air samplers for monitoring airborne culturable bacteria. AB - Airborne culturable bacteria were monitored at five locations (three in an office/laboratory building and two in a private residence) in a series of experiments designed to compare the efficiency of four air samplers: the Andersen two-stage, Burkard portable, RCS Plus, and SAS Super 90 samplers. A total of 280 samples was collected. The four samplers were operated simultaneously, each sampling 100 L of air with collection on trypticase soy agar. The data were corrected by applying positive hole conversion factors for the Burkard portable, Andersen two-stage, and SAS Super 90 air samplers, and were expressed as log10 values prior to statistical analysis by analysis of variance. The Burkard portable air sampler retrieved the highest number of airborne culturable bacteria at four of the five sampling sites, followed by the SAS Super 90 and the Andersen two-stage impactor. The number of bacteria retrieved by the RCS Plus was significantly less than those retrieved by the other samplers. Among the predominant bacterial genera retrieved by all samplers were Staphylococcus, Bacillus, Corynebacterium, Micrococcus, and Streptococcus. PMID- 11192220 TI - Performance of Air-O-Cell, Burkard, and Button Samplers for total enumeration of airborne spores. AB - Performance of three devices used for the total enumeration of airborne spores the Air-O-Cell sampling cassette, the Burkard personal volumetric air sampler, and the Button Aerosol Sampler--was evaluated under controlled laboratory conditions. The first two are glass-slide impactors; the third collects spores on a filter. The samplers were challenged with 0.44-5.10 microm polystyrene latex particles and five microorganisms of 0.84-3.07 microm mean aerodynamic diameter: Streptomyces albus, Bacillus subtilis, Cladosporium cladosporioides, Penicillium brevicompactum, and Penicillium melinii. An optical particle counter measured the particle concentrations upstream and downstream of each sampler, and thus determined the physical collection efficiency of the three samplers. Collection efficiency of the Button Aerosol Sampler was close to 100% for the entire particle size range studied. The cut-off size of each impactor was 2.3-2.4 microm. Acridine orange (with epifluorescent microscopy) and lactophenol cotton blue (with bright light microscopy) staining techniques were used for the microscopic enumeration of spores. No significant difference in microscopic counts was found (at the 95% significance level) when using these two techniques with the Button Aerosol Sampler filters. When the lactophenol cotton blue staining was used to compare total microbial counts yielded by all three samplers, the Button Sampler showed significantly higher counts for the smaller size microorganisms (B. subtilis and C. cladosporioides). For the larger microorganisms (P. brevicompactum and P. melinii) all three samplers yielded similar results. Uniformity of particle deposition on the collection surface was highest for the Button Aerosol Sampler due to the design of its inlet. Thus, the filter collection method used with the Button Aerosol Sampler is suitable and can be advantageous for the enumeration of total airborne spores. PMID- 11192222 TI - Effects on heat stress of a flame-retardant ensemble for aluminum smelters. AB - A common belief is that a flame-retardant clothing ensemble will increase the level of heat stress over ordinary cotton work clothes. This is supported by bench tests on fabrics that indicate higher insulation and vapor resistance values for flame-retardant clothing. This research compared a flame-retardant clothing ensemble for an aluminum smelter (Zirpo wool shirt and FR8 denim pants) with typical cotton work clothing. Four young men walked on a treadmill at two work levels inside a climatic chamber under controlled conditions of heat stress. During each test, heart rate, core temperature, and skin temperatures were continuously monitored and recorded every 5 min. After a physiological steady state was achieved, temperature and humidity were slowly increased to maintain a relative humidity of 50%. The critical condition was the time when thermal regulatory control was lost (called the inflection point, marked by a steady increase in core temperature). The climatic conditions at the inflection point were used to assign a critical wet-bulb globe temperature (WBGT). A three-way analysis of variance examined the effects on critical WBGT of clothing, work level, subjects, and the interaction between clothing and work level. There were no significant findings. Therefore, there should be no difference in the level of heat stress between the two clothing ensembles under the same environmental and work conditions. PMID- 11192221 TI - Coast Guard exposure to gasoline, MTBE, and benzene vapors during inspection of tank barges. AB - A field study was conducted June through August 1996 in an attempt to quantify short-term exposure levels to Coast Guard personnel performing routine inspection activities aboard commercial tank barges carrying gasoline. Transfer and fleeting operations were monitored in the ports of Pittsburgh, Pa., Huntington, W.Va., Baton Rouge, La., and Galveston, Tex. A total of 43 personal and 68 area samples were analyzed for benzene and total hydrocarbons as gasoline ("gasoline"). Results can be summarized as follows: Personal exposure to benzene gave 15-min time-weighted-average (TWA) results ranging from <0.10 to 0.50 ppm. Area benzene levels ranged from <0.04 to 170 ppm. Personal monitoring for gasoline revealed a range of <2.0 to 590 mg/m3 with a GM of 23 mg/m3. Area sample results for gasoline ranged from 1.7 to 90,000 mg/m3. Twelve personal samples were collected for methyl-tert butyl ether (MTBE). Only two of these were above the limit of detection and had 15-min time-weighted averages of 22 ppm and 1.3 ppm. Eighteen MTBE area samples ranged in value from <3.0 to 38 ppm. Although none of the personal samples met or exceeded proposed or established short-term exposure standards, many of the area sampling results indicated that a significant risk of acute exposure exists in the vicinity of valves, pressure lines, and connections. This includes anticipated sources such as pressure vent valves as well as unexpected sources resulting from structural deficiencies onboard the vessels. These results further emphasize the value of safe work practices and proper vessel maintenance in controlling exposure to harmful chemicals. PMID- 11192223 TI - Determining parameters of lognormal distributions from minimal information. AB - The lognormal distribution has a number of properties that do not lend themselves to simple "back-of-the-envelope" calculations. Mathematical relationships are presented for the basic parameters of the large population lognormal distribution as a function of characteristics available to, or needed by, the risk analyst. A freeware computer program called LOGNORM4 has been written to take the tedium out of determining various characteristics of lognormal distributions, given 1 of 15 sets of values that uniquely specify a lognormal distribution. PMID- 11192224 TI - Hydrocarbon solvent exposure data: compilation and analysis of the literature. AB - An occupational exposure database for hydrocarbon solvent end-use applications was constructed from the published literature. The database provides exposure assessment information for such purposes as regulatory risk assessments, support of industry product stewardship initiatives, and identification of applications in which limited exposure data are available. It is quantitative, documented, and based on credible data. Approximately 350 articles containing quantitative hydrocarbon solvent exposure data were identified using a search of computer databases of published literature. Many articles did not report sufficient details of the exposure data for inclusion in the database (e.g., full-shift exposure or task-based exposure data). Others were excluded because only limited summary statistics were provided, which precluded statistical analysis of the data (e.g., arithmetic mean concentration presented, but no sample number). Following evaluation, 16,880 hydrocarbon solvent exposure measurements from 99 articles were entered into a database for analysis. Methods used to identify and evaluate published solvent exposure data are described along with more detailed analysis of worker exposure to hydrocarbon solvents in three major end-use applications: painting and coating, printing, and adhesives. Solvent exposures were evaluated against current ACGIH threshold limit values (TLVs) and trends were identified. Limited quantitative data are available prior to 1970. In general, reported hydrocarbon solvent exposures decreased fourfold from 1960 to 1998, were below the TLVs applicable to specific hydrocarbon solvents at the time, and on average have been below 40% of the TLV since 1980. The database already has proved valuable; however, the utility of published exposure data could be further improved if authors consistently reported essential data elements and supporting information. PMID- 11192225 TI - Building materials used in construction can affect indoor fungal levels greatly. AB - This article summarizes the results of a fungal investigation of a new, seven story, 170-room hotel. The owners of the building were refused an occupancy permit by local building officials because of concerns about fungal contamination. This article discusses the processes that were used to investigate and abate the fungal concerns in this building. This investigation involved comparing fungal infestation levels in various building materials, including two different types of gypsum wallboard. During initial testing the indoor air concentrations of problematic fungi were up to 50 times higher than outdoor levels. After the removal of the fungal-infested materials and the replacement with more acceptable materials, the indoor air concentration of problematic fungi dropped to less than one-fourth of outdoor levels. PMID- 11192226 TI - PAT Program report: background and current status. Proficiency Analytical Testing. PMID- 11192227 TI - ELPAT Program report: background and current status. Environmental Lead Proficiency Analytical Testing. PMID- 11192228 TI - Asthma management: curtailing costs and improving patient outcomes. AB - As our understanding of asthma has evolved, so have pharmaceutical strategies for managing this disorder. Once considered a disorder of airway smooth muscle, asthma now is regarded primarily as a chronic inflammatory disorder of the airways. Traditional therapy sought to suppress bronchoconstriction and other signs and symptoms of asthma when they occurred, but contemporary strategies center on managing the underlying inflammation through long-term medications intended to reduce the overall risk of acute attacks. Direct and indirect costs of illness for asthma were estimated at $6.2 billion in 1990. Undoubtedly the costs are considerably higher today due to the increasing prevalence of the disorder. The costs associated with the illness are not distributed evenly among the 15 million Americans with asthma. About 20% of the patients account for 80% of the expenditures. By identifying the high-cost patients and educating them regarding the proper use of medication, it may be possible to curtail costs associated with asthma. Healthcare professionals, especially in their role as educators, are critical to reducing morbidity, mortality, and costs associated with asthma patients. PMID- 11192229 TI - Risk factors for pediatric asthma emergency visits. Milwaukee Childhood Asthma Project Team. AB - The purpose of this study was to identify risk factors for pediatric asthma emergency department (ED) visits. A cross-sectional sample of 307 families (24%) responded to a mailed survey. Respondents were similar to the target population of 2487 children with asthma. Thirty-seven percent of respondents had two or more asthma ED visits in the past year. Asthma ED use was associated with persistent asthma symptoms, parents without high school diplomas, age under 4 years, African American race/ethnicity, use of written care plans, and use of spacers at school. The latter two variables were associated with severe asthma. High-risk children can be targeted for office-based medical care. PMID- 11192230 TI - Value of bronchial challenge in scuba diving candidates. AB - Bronchial challenges were effected with carbachol in 76 subjects who were candidates for a scuba diving group. Bronchial reactivity was assessed through airway resistance and forced expiratory volume in 1 sec (FEV1) measurements. Medical interrogation had revealed symptoms of recent (RA) or ancient (AA) asthma, or allergic rhinitis (AL). Nearly half of the subjects (47%) presented bronchial hyperresponsiveness (BHR), which was much more frequent in the RA group, but whose strength did not depend on clinical presentation. Prevalence of BHR was fairly high (36%) in the AL group. BHR constituted a contraindication to scuba diving because it may promote pulmonary barotrauma. PMID- 11192231 TI - Comparable bronchodilation with hydrofluoroalkane-134a (HFA) albuterol and chlorofluorocarbons-11/12 (CFC) albuterol in children with asthma. AB - This was an open-label, parallel group, randomized, age-stratified, multicenter study designed to compare the safety and efficacy of regular use of albuterol formulated in hydrofluoroalkane-134a (HFA albuterol) and albuterol formulated in chlorofluorocarbons-11/12 (CFC albuterol) in children with asthma. Children age 4 11 years using a short-acting inhaled beta2-agonist for 6 months to manage stable asthma, and with a prestudy forced expiratory volume in 1 sec (FEV1) of >50% predicted after withholding short-acting inhaled beta2-agonists for at least 6 hr, an increase in FEV1 > or = 12% within 30 min after two puffs of CFC albuterol, and the capability to comply with medication withholding requirements were eligible for study entry. After screening evaluation, patients entered a minimum 7-day run-in period. On study day 1 spirometry and a baseline 12-lead electrocardiogram (ECG) were performed, pulse and blood pressure were measured, and patients self-administered two puffs of their randomized study drug, either HFA albuterol or CFC albuterol. Serial spirometry was performed over 6 hr after study drug dosing. Pulse and blood pressure were measured just prior to each spirometry and a 12-lead ECG was performed at 60 min postdose. Patients took two puffs of their study drug four times a day for 4 weeks. At study week 4, study day 1 procedures were repeated. Patients maintained a daily diary of morning (A.M.) and evening (P.M.) peak expiratory flow (PEF), daytime asthma symptom scores, nighttime asthma sleep disturbance scores, and study drug use. Demographics and baseline characteristics of the 63 patients randomized to HFA albuterol (33) and CFC albuterol (30) were similar. No significant differences were found between the HFA albuterol and CFC albuterol treatment groups for any of the primary or secondary FEV1 efficacy variables either at study day 1 or study week 4. No significant differences were noted between treatment groups for A.M. and P.M. PEF, individual asthma symptom scores, nighttime asthma sleep disturbance scores, and rescue study drug use over the 4-week study. No significant differences were found between the two treatment groups for change from predose in heart rate, systolic and diastolic blood pressure, and 12-lead ECG intervals at either study day 1 or study week 4. Adverse event reporting was similar for the two treatment groups. In this study, with regular use of HFA albuterol in children with asthma, there was a similar safety profile and comparable bronchodilator efficacy as with CFC albuterol. PMID- 11192232 TI - Descriptive epidemiology of asthma in Trinidad, West Indies. AB - This cross-sectional study documents the demographic features of asthmatics seeking acute asthma care at four institutions on the island of Trinidad from January 1 to December 31, 1997. More than 15,000 (15,035) different patients made 27,353 visits during the study period. Pediatric and adolescent male patients outnumbered females, but this was reversed in patients aged 20-69 years. Frequency of visits per patient ranged from 1 to 242. Significant variation in monthly admissions was observed; admission rates were highest in the last quarter of the year but were lowest in July and August. The overall crude prevalence rate was estimated at 1.71 per 100 (range 1.16-2.34). PMID- 11192233 TI - Allergy history does not predict skin test reactivity in asthmatic children. AB - We prospectively assessed how well patient report of allergy to cat, dust mite, and grass predicted the results of skin prick testing to those allergens in 95 asthmatic children. Children between 4 and 18 years old with physician-documented asthma provided a detailed standardized allergy history and then underwent skin prick testing. The children were categorized by asthma severity. The diagnostic accuracy, which was the primary outcome measure, as well as sensitivity, specificity, and positive and negative predicted values were calculated for allergy history with regards to skin test reactivity. The diagnostic accuracy of allergy history in identifying skin test reactivity was 65%, 50%, and 56% for cat, dust mite, and grass, respectively. Asthma severity did not affect the diagnostic accuracy. Allergy history was a poor predictor of skin test reactivity in this group of asthmatic children. PMID- 11192234 TI - The influence of polymorphism at position 16 of the beta2-adrenoceptor on the development of tolerance to beta-agonist. AB - Polymorphism at position 16 of the beta2-adrenoceptor alters receptor down regulation in vitro. Our aim was to compare the development of tolerance to beta agonist in homozygous Gly-16 patients with patients harboring the "wild" genotype (homozygous Arg-16) during regular treatment with salmeterol. In a prospective, randomized, double-blind, placebo-controlled, cross-over study, 20 subjects with mild to moderate asthma (10 Gly-16, 10 Arg-16) received 2 weeks of treatment with inhaled salmeterol 100 microg b.i.d. Thereafter, dose responses to inhaled salbutamol were constructed for forced expiratory volume in 1 sec (FEV1), heart rate, QTc interval, serum potassium and glucose, and finger tremor. The protective effect of salbutamol against adenosine monophosphate (AMP) challenge was also measured. Salmeterol resulted in a significant reduction in the area under curve (AUC) for FEV1 (p = 0.01), heart rate (p = 0.01), QTc interval (p = 0.01), and tremor (p = 0.05), and in the maximum responses for FEV1 (p = 0.05), heart rate (p = 0.02), and glucose (p = 0.02). The protective effect of salbutamol against AMP was reduced by 3.61 doubling doses (p < 0.001). However, differences between Gly-16 and Arg-16 patients were small and nonsignificant. Thus, although tolerance is influenced in vitro by polymorphism of the beta2 adrenoceptor, the magnitude of between-genotype differences in vivo is unlikely to be significant. PMID- 11192235 TI - Relapse following treatment of acute asthma in the emergency department. AB - Most patients presenting to the emergency department (ED) with acute asthma will have some, if not significant, relief of respiratory distress following treatment. The majority of patients are discharged to home; however, a significant portion of patients relapse and require urgent medical treatment. Many patients have continued respiratory symptoms and impairment in activities of daily living after ED treatment. In a large multicenter trial, we found that 17% of patients relapse within 2 weeks, requiring urgent medical treatment. The factors associated with asthma relapse were a history of numerous ED visits over the previous year, a history of urgent clinic visits over the previous year, use of a home nebulizer, multiple asthma triggers, and duration of symptoms between 1 and 7 days. In other studies, we found that many patients relapse before they can see their primary care physician, and that the lack of an identifiable primary care physician is associated with a higher incidence of relapse. Two interventions have been shown in studies to decrease the rate of relapse. The first, the administration of corticosteroids, has been adopted into general medical practice. Despite the routine use of corticosteroids following ED treatment, however, relapse remains a substantial problem. The second intervention involves focused long-term management by an asthma specialist. Several projects have demonstrated the efficacy of this approach in decreasing ED visits. Although it is time- and resource-intensive, this approach may be necessary for those patients who have frequent ED visits. Whether this approach is generalizable has yet to be demonstrated. In this article, we review the previous work on asthma relapse and suggest areas for further study. PMID- 11192237 TI - School preparation for the asthmatic student. AB - Questionnaires given to school nurses were used to collect data regarding emergency asthma equipment and plans. Sixty-three percent reported <10 asthmatic visits per month, 25% reported 10-50, and 12% reported >50. Only 20% of school nurses reported that 75%-100% of asthmatic students had an emergency plan, and 24% did not know if asthmatic students had a plan. Only half of the nurses had input into the plan. Equipment varied: 16% had oxygen, 45% had peak flow meters, 0% had MDIs, and 20% had nebulizers available. Many asthmatic students lack emergency plans, and many school nurses are not involved in the plans. PMID- 11192236 TI - Atopic status and level of bronchial responsiveness in parents of children with acute bronchiolitis. AB - To examine whether children with a genetic predisposition to asthma are more likely to be afflicted with bronchiolitis, we studied 122 parents of infants who were hospitalized with the diagnosis of acute bronchiolitis (index group) and 120 parents of children who had never suffered from this disease (control group). The parents underwent bronchial challenge testing with methacholine and skin prick testing with common airborne allergens, and gave blood specimens for measurement of serum total IgE. There was no difference in atopic status, as assessed by the prevalence of atopy (at least one positive response to the allergens tested) or by serum total IgE levels, between index and control parents. The prevalence of bronchial hyperresponsiveness (BHR) (concentration of methacholine causing a 20% reduction in forced expiratory volume in 1 sec [PC20] < 18 mg/mL) was higher in index parents than in control parents (17.2% vs. 7.5%, p = 0.02). Bronchial responsiveness (BR) index was significantly higher in index parents than in control parents (1.135 +/- 0.088 vs. 1.104 +/- 0.071, p < 0.01). Parents of children who were hospitalized with acute bronchiolitis showed a higher level of BR, but not atopy. This suggests that in terms of BHR, there may be a genetic predisposition to the development of bronchiolitis. PMID- 11192238 TI - Synthesis of tumor associated sialyl-T-glycopeptides and their immunogenicity. AB - Sialyl-T-glycopeptides were synthesized by solid-phase techniques, using a PEGA resin as the solid support. An appropriately protected building block containing alpha-Neu5Ac-(2 --> 3)-beta-Gal-(1 --> 3)-alpha-GalN3-(1-->) attached to Fmoc Thr/Ser-OPfp was employed in a solid phase glycopeptide assembly of a 10-mer glycopeptide, using a general Fmoc/OPfp-ester strategy. Reduction of the azido group of the GalN3 residue was effected on solid-phase, using DTT and DBU. After acidolytic cleavage from the resin, the methyl ester of the sialic acid residue and acetyl groups were removed with 30% NaOMe/MeOH in MeOH and water pH 14, at 30 degrees C for 2 h. At this low temperature, the highly basic conditions did not result in any detectable beta-elimination. However, one O-acetyl group, located at the 2-position of the Gal was resistant to hydrolysis. To remove this remaining acetyl group, reaction with hydrazine hydrate in CHCl3 and MeOH at room temperature for 2.5 h was successful. The two target sequences of sialyl-T glycopeptides were obtained in good yield. In contrast to the the analogs carrying the T-antigen, the Sial-T-glycopeptides were nonimmunogenic, supporting the idea that the sialylation is a method of circumventing the recognition by the immune system. PMID- 11192239 TI - Alpha-azido acids for direct use in solid-phase peptide synthesis. AB - Several new alpha-azido acids have been synthesized and their use in solid-phase peptide synthesis has been demonstrated. The azido group allows for high activation of the carboxyl group as an acid chloride without formation of byproducts and with no detectable racemization. An analog of Leu-enkephalin has been prepared and tested in the mouse vas deferens and guinea pig ileum bioassays: it displays moderate activity at the delta-opiod receptor. PMID- 11192240 TI - Structural properties of DNO investigated with pyrene excimer formation. AB - Four diamino acid-Nalpha-substituted oligopeptide (DNO) oligomers substituted with pyrenyl as photophysical probes were synthesized. The excimer formation and ground-state association of the pyrenyl groups were investigated by means of absorption and steady-state fluorescence spectroscopy together with time-resolved fluorescence techniques. The photophysical parameters obtained from the different derivatives reflect the secondary structural properties of the DNO backbones. PMID- 11192241 TI - Solid-phase synthesis of MEN 11270, a new cyclic peptide kinin B2 receptor antagonist. AB - An efficient synthesis of the cyclic decapeptide MEN 11270 [H-DArg1-Arg2 Pro3 Hyp4-Gly5-Thi6-Dab7-DTic8-Oic9-Arg10 c(7gamma - 10alpha)] was developed. Two three-dimensional orthogonal strategies were applied and compared: Fmoc/Tos/Boc (procedure A) and Fmoc/Pmc/Dde (procedure B). Both resulted in a 23-step strategy comprising the stepwise solid-phase chain assembly of the linear protected peptide, partial deprotection, solution-phase cyclization and final full deprotection. The stepwise assembly of the linear peptide was optimized by double coupling and acylation time prolongation for critical residues (Tic, Dab, Thi, Pro). O-(7-azabenzotriazol-1-yl)-N,N,N',N' tetramethyluronium (HATU) was preferred as coupling reagent for Dab. In the cyclization step, the partial racemization of Arg10 (31% using 1-ethyl-3-(3'-dimethyl-aminopropyl) carbodiimide/1-hydroxybenzotriazole (EDC/HOBt) as activation system) was reduced to 3% with HATU. The final deprotection was performed in the presence of dimethylsulfide (procedure A) and thiocresol (procedure B) as scavengers, to avoid the sulfation of Hyp side chain. The final compound and the main by products were characterized by mass spectroscopy (MS), nuclear magnetic resonance (NMR) and racemization test. Procedure B produced operationally simpler and more efficient results than A (28% overall yield versus 4%). PMID- 11192242 TI - An imidazoline pseudodipeptide suitable for solid phase peptide synthesis. AB - This paper describes the synthesis of two diastereoisomers of an imidazoline dipeptide mimetic (a 4,5 dihydroimidazole-4-carboxylic acid), suitably protected for incorporation into solid phase peptide synthesis (SPPS) using the Fmoc protocol, from a phenylalanine-derived thioimidate and an alpha,beta diaminopropanoic acid ester, followed by protecting group manipulation. PMID- 11192243 TI - Quantitative small-animal surrogate to evaluate drug efficacy in preventing wear debris-induced osteolysis. AB - Individuals who suffer from severe joint destruction caused by the various arthritidies often undergo total joint arthroplasty. A major limitation of this treatment is the development of aseptic loosening of the prosthesis in as many as 20% of patients. The current paradigm to explain aseptic loosening proposes that wear debris generated from the prosthesis initiates a macrophage-mediated inflammatory response by resident macrophages, leading to osteoclast activation and bone resorption at the implant interface. No therapeutic interventions have been proved to prevent or inhibit aseptic loosening. The development of therapeutic strategies is limited due to the absence of a quantitative surrogate in which drugs can be screened rapidly in large numbers of animals. We have previously described a model in which titanium particles implanted on mouse calvaria induce an inflammatory response with osteolysis similar to that observed in clinical aseptic loosening. Here, we present new methods by which the osteolysis in this model can be quantified. We determined that 6-8-week-old mice in normal health have a sagittal suture area of 50 (+/-6) microm2, which contains approximately five osteoclasts. As a result of the titanium-induced inflammation and osteolysis, the sagittal suture area increases to 197 (+/-27) microm2, with approximately 30 osteoclasts, after 10 days of treatment. The sagittal suture area and the number of osteoclasts in the calvaria of sham-treated mice remained unchanged during the 10 days. We also determined the effects of pentoxifylline, a drug that blocks the responses of tumor necrosis factor-alpha to wear debris, and the osteoclast inhibitor alendronate. We found that both drugs effectively block wear debris-induced osteolysis but not osteoclastogenesis. In conclusion, we found the measurements made with this model to be reproducible and to permit quantitative analysis of agents that are to be screened for their potential to prevent aseptic loosening. PMID- 11192244 TI - In vivo kinematics of total knee arthroplasty: flat compared with concave tibial joint surface. AB - This study evaluated the influence of the geometric configuration of the tibial joint area on the kinematics of the knee. Twenty-two patients with noninflammatory arthritis and minor preoperative deformity were studied. They each received an AMK total knee replacement with retention of the posterior cruciate ligament. Eleven patients without any knee abnormalities were used as controls. The patients were stratified to either the flat (terminology of the manufacturer: standard) or concave (terminology of the manufacturer: constrained) polyethylene insert (n = 11 in each group). Knee kinematics were assessed 1 year after the operation by having the patient ascend a platform corresponding to an extension of the knee from 50 to 70 degrees of flexion. During this motion, two film-exchangers simultaneously exposed six to 13 pairs of serial stereoradiographs. The concave geometric configuration of the tibial insert resulted paradoxically in increased anterior-posterior translations compared with the flat insert but no significant change of rotations and translations in the other directions. Compared with normal knees, the most obvious abnormality was increased anterior-posterior translations (p < 0.004). At 50 degrees of flexion, the implants with the flat tibial polyethylene insert had displaced 2 times and the concave ones had displaced 2.5 times more posteriorly than the normal knees (p < or = 0.001). Less internal tibial rotation was also recorded in the flexed positions for both types of inserts compared with the normal knees (p < 0.02). Four knees in four patients, who reported symptoms of instability and abnormal knee function, showed significantly increased proximal displacement of the center of the tibial plateau in the flexed position. The findings suggest that current prosthetic designs and surgical technique do not restore normal knee kinematics and indicate that design improvements should rely on in vivo kinematic studies. PMID- 11192245 TI - Plate fixation of prostheses after segmental resection for bone tumours. AB - This study investigated the concept of using plates to attach endoprostheses to bone after segmental resection for bone tumours in an animal model. Titanium alloy plates integrated with the prosthesis and coated with hydroxyapatite were attached to bone by screws. This type of uncemented fixation relied on the induction of periosteal bone formation into and around the plates to secure the implant to bone. Two, three, and six-slotted plate designs were investigated. On retrieval, each plate was securely fixed by new bone. Bone apposition on the external surface of the plates occurred through a combination of periosteal bone production, invasion of bone through slots in the plate, and bone growth over the ends of the plates. Most plates became incorporated into a remodelled cortex. Higher bone turnover rates (microm day(-1)) were seen in bone in the slots of the plate compared with normal cortical bone turnover (p < 0.05). Significantly higher rates of turnover were measured beneath slotted parts of the plates compared with regions below the unslotted parts (p < 0.05). The cross-sectional area of bone surrounding the six-plate implant design was significantly higher than that of the three-plate (p < 0.05) and two-plate (p < 0.05) designs. In addition, significantly more bone formed adjacent to the six-plated implant design compared with that in the contralateral limb (p = 0.002). However, no significant difference was found when the total cortical area around the three plated design was compared with that of the contralateral limb (p = 0.63). In contrast, significantly less bone was measured adjacent to the two-plate design than in the untreated limb (p = 0.001). Image analysis also demonstrated increased cortical porosity adjacent to the six-plate design compared with the three-plate (p = 0.004) and two-plate (p < 0.05) designs. Finite element analysis demonstrated that the six and three-plate designs increased the second moment of area compared with that in the left tibia (p = 0.003 and 0.066, respectively). However, the attachment of the more flexible two-plate design did not significantly increase the second moment of area compared with that in the contralateral limb (p = 0.235). It was concluded that due to both mechanical and biological effects, the hydroxyapatite-coated plate designs generated new bone that enhanced fixation and encouraged plate integration into the load-bearing structure of the cortex. This method of fixation may be an alternative to the use of intramedullary cemented stems in patients requiring bone tumour implants and may be the only way to preserve the joint in difficult cases where only short segments of bone remain. PMID- 11192246 TI - Pamidronate prevents bone loss associated with carrageenan arthritis by reducing resorptive activity but not recruitment of osteoclasts. AB - Carrageenan arthritis is associated with high-turnover bone loss. We sought to determine whether the bisphosphonate pamidronate can modify this effect of inflammatory arthritis. Sixty mature, New Zealand White rabbits were randomly assigned to five groups: normal; normal with a therapeutic dose of pamidronate (300 microg/kg/day, administered subcutaneously); arthritis (induced in the right tibiofemoral joint with 10 intraarticular carrageenan injections); arthritis with a therapeutic dose of pamidronate (300 microg/kg/day, subcutaneous); and arthritis with a low dose of pamidronate (7.5 microg/kg/day, subcutaneous). All animals received the fluorochrome calcein green (0.5 g/l/day) in drinking water ad libitum from days 21 to 49. Undecalcified, transverse sections of the distal femur were photographed or imaged to determine bone volume; new bone volume; resting, eroded, osteoid, and osteoblast perimeters; and osteoclast number. Results were evaluated with analysis of variance and pairwise Bonferroni's tests. In trabecular bone adjacent to the joint affected by carrageenan arthritis, resting perimeter was substantially reduced compared with normal joints, and primary indices of osteoblast and osteoclast activity were abnormally high (p < 0.001). Daily treatment with a therapeutic dose of pamidronate (300 microg/kg/day, subcutaneous) during the induction of arthritis significantly decreased new bone volume, osteoid perimeter, and osteoblast perimeter compared with the untreated arthritis group (p < 0.001). Osteoclast number and eroded perimeter remained abnormally high despite treatment with pamidronate. The concomitant increase of bone volume and these osteoclast indices show that pamidronate prevents bone loss in this model of experimental inflammatory arthritis by inhibiting the resorptive activity, but not the formation or recruitment, of osteoclasts. These findings are relevant to the use of bisphosphonates in the treatment of rheumatoid arthritis. PMID- 11192247 TI - Enhanced proliferation and differentiation of human articular chondrocytes when seeded at low cell densities in alginate in vitro. AB - Dedifferentiated human articular chondrocytes exhibited a wide variation in their capacity to proliferate and redifferentiate in an alginate suspension culture system. The greatest extent of proliferation and redifferentiation was seen to be dependent on the formation of clonal populations of chondrocytes and correlated inversely with the initial cell seeding density. Redifferentiating chondrocytes seeded at low density (1 x 10(4) cells/ml alginate) compared with chondrocytes that were seeded at high density (1 x 10(6) cells/ml alginate) showed a nearly 3 fold higher median increase in cell number. a 19-fold greater level of type-II collagen mRNA expression, a 4-fold greater level of aggrecan mRNA expression, and a 6-fold greater level of sulfated glycosaminoglycan deposition at 4 weeks of culture. Matrix molecules from low-density cultures were assembled into chondrocyte-encapsulated, spherical extracellular matrices that were readily visualized in sections from 12-week cultures stained with antibodies against types I and II collagen and aggrecan. Ultrastructural analysis of 12-week low density cultures confirmed the presence of thin collagen fibrils throughout the matrix. PMID- 11192248 TI - Viscoelastic properties of chondrocytes from normal and osteoarthritic human cartilage. AB - The deformation behavior and mechanical properties of articular chondrocytes are believed to play an important role in their response to mechanical loading of the extracellular matrix. This study utilized the micropipette aspiration test to measure the viscoelastic properties of chondrocytes isolated from macroscopically normal or end-stage osteoarthritic cartilage. A three-parameter standard linear solid was used to model the viscoelastic behavior of the cells. Significant differences were found between the mechanical properties of chondrocytes isolated from normal and osteoarthritic cartilage. Specifically, osteoarthritic chondrocytes exhibited a significantly higher equilibrium modulus (0.33 +/- 0.23 compared with 0.24 +/- 0.11 kPa), instantaneous modulus (0.63 +/- 0.51 compared with 0.41 +/- 0.17 kPa), and apparent viscosity (5.8 +/- 6.5 compared with 3.0 +/ 1.8 kPa-s) compared with chondrocytes isolated from macroscopically normal, nonosteoarthritic cartilage. The elastic moduli and relaxation time constant determined experimentally in this study were used to estimate the apparent biphasic properties of the chondrocyte on the basis of the equation for the gel relaxation time of a biphasic material. The differences in viscoelastic properties may reflect alterations in the structure and composition of the chondrocyte cytoskeleton that have previously been associated with osteoarthritic cartilage. Coupled with earlier theoretical models of cell-matrix interactions in articular cartilage, the increased elastic and viscous properties suggest that the mechanical environment of the chondrocyte may be altered in osteoarthritic cartilage. PMID- 11192249 TI - Biomechanical regulation of matrix metalloproteinase-9 in cultured chondrocytes. AB - Abnormal mechanical loading of joints may induce degeneration of articular cartilage. Shear stress is one mode of mechanical loading that may regulate chondrocyte metabolism. We investigated the mechanism by which shear stress induces the gene encoding matrix metalloproteinase-9, a mediator of the progressive degradation of articular cartilage in osteoarthritis. In vitro experiments using passaged rabbit chondrocytes in monolayer culture subjected to a shear stress of 16 dyn/cm2 (1.6 Pa) in a flow channel showed increased expression of the matrix metalloproteinase-9 gene. The induction of matrix metalloproteinase-9 appeared to depend on a region in the 5' promoter of the gene that contains a 12-0-tetradecanoylphorbol 13-acetate-responsive element. Transfection experiments using a construct containing a luciferase reporter driven by a 12-0-tetradecanoylphorbol 13-acetate-responsive element indicated that shear stress activated a 12-0-tetradecanoylphorbol 13-acetate-responsive element-mediated transcription in chondrocytes. Similar experiments showed that shear stress induced a matrix metalloproteinase-9 promoter construct (matrix metalloproteinase-9-luciferase). Shear stress activated c-Jun NH2-terminal kinase, extracellular signal-regulated kinase, and p38. Transfection of matrix metalloproteinase-9-luciferase together with the dominant negative mutant of c Jun NH2-terminal kinase, but not with that of extracellular signal-regulated kinase or p38, attenuated the shear-induced matrix metalloproteinase-9 promoter activity. In addition, transfection of constructs encoding dominant negative mutants of Ras, Rac, and Cdc42 attenuated the induction of c-Jun transcriptional activity by shear stress. Thus. shear stimulation of chondrocytes stimulates Ras, Rac, and Cdc42, which subsequently activate c-Jun NH2-terminal kinase to induce a 12-0-tetradecanoylphorbol 13-acetate-responsive element-mediated expression of matrix metalloproteinase-9. PMID- 11192250 TI - Delamination rates of tissue flaps used in articular cartilage repair. AB - A popular strategy in the treatment of articular cartilage lesions involves the introduction of cell suspensions into the defect void and its closure with a periosteal flap (autologous chondrocyte transplantation technique). We applied this methodology in goats and discovered that all sutured flaps (n = 6 animals) became detached from nonimmobilized joints during the recovery period. The purpose of this study was to ascertain whether postoperative restriction of joint movement could prevent the delamination of flaps. Partial-thickness defects were created in the knee joint cartilage of 27 goats. These defects were then filled with a fibrin matrix and covered with periosteal (n = 6) or fascial (n = 21) flaps, which were sutured with simple, interrupted stitches to the surrounding tissue. The joints were immobilized by means of a modified Robert Jones bandage for periods of 2-6 weeks, after which time they were inspected for the absence or presence of flaps. In four animals, joint immobilization for 3 weeks was followed by free movement for a similar period. Four of the six periosteal flaps and two of the 21 fascial ones became delaminated after the period of immobilization. In the four goats permitted 3 weeks of free joint movement following a similar period of joint immobilization, all flaps (which had been retained up to the end of the immobilization period) became detached. These findings indicate that joint immobilization hinders the delamination of flaps but that this restriction of movement must be sustained for an undefined period of time. The nature of the tissue used for flaps also influences their rate of retention by immobilized joints. PMID- 11192251 TI - Quantitative assessment of in vivo bone regeneration consolidation in distraction osteogenesis. AB - We present a new method for quantitatively assessing the consolidation of bone regeneration by performing distraction osteogenesis in micropigs. We measured in vivo stiffness using a newly developed, revolving, bone-healing meter. After the micropigs were killed, we obtained maximum torsional moment data for the regenerated bones by destructive mechanical testing, and we then correlated these data with the data for stiffness. We found a highly significant regression between in vivo stiffness and maximum torsional moment (r2 = 0.80), suggesting that monitoring stiffness may be useful for the prediction of bone regeneration in distraction osteogenesis. Therefore, our method may be a reliable tool for future quantitative monitoring of healing progress in patients with healing bones or in animal studies addressing treatments to increase bone formation in long bone defects. PMID- 11192252 TI - Cellular contribution of bone graft to fusion. AB - Although a number of studies have examined the fate of graft-derived cells during the process of fusion, there remains no consensus regarding their exact contribution to bone formation within the fusion mass. We developed two chimeric mouse isograft fusion models that allowed us to track the fate of graft cells within the host fusion bed. Cortical/cancellous bone graft (1:1 ratio of pelvic to vertebral body bone) from male mice was placed between (a) the tibia and fibula or (b) the coccygeal spine transverse processes of syngeneic female hosts. Both models were characterized histologically and histochemically. Graft-derived cells were then identified by fluorescent in situ hybridization for Y-chromosome sequences present in only the graft (male) cells. When the fusion mass was healing but not yet fused (at 1 and 2 weeks), numerous graft-derived cells were observed throughout the fusion site. The predominant graft-derived cell types included chondrocytes, osteoblasts, and fibroblasts. Chondrocytes arose from precursor cells in the graft de novo. as cartilage was not transplanted during the surgical procedure. By the time a mature fusion mass had formed (at 6 weeks), graft-derived cells persisted as osteocytes within the cortical rim surrounding the fusion mass. These osteocytes likely differentiated from graft-derived precursors that had directly formed bone, because transplanted osteocytes within cortical bone graft fragments were noted to rarely survive even at 1 and 2 weeks. Collectively, our results demonstrate for the first time that bone graft contributes cells that, in conjunction with host cells, directly form bone within the fusion mass during all phases of fusion rather than just the early phases. PMID- 11192253 TI - Extracellular collagen regulates expression of transforming growth factor-beta1 gene. AB - A complex interrelationship exists between the extracellular matrix and cytokine signaling in articular chondrocytes. We sought to determine whether the extracellular matrix serves as a regulatory component of transforming growth factor-beta1 expression. Bovine articular chondrocytes were isolated and resuspended in alginate, yielding final extracellular protein concentrations of 0 to 1.5% (wt/vol) for type-II or type-I collagen. Cultures were maintained for 7 days in the presence or absence of transforming growth factor-beta1-supplemented medium (10 ng/ml). The amount of transforming growth factor-beta1 mRNA was examined with quantitative competitive reverse transcription-polymerase chain reaction analysis. The results indicate that exogenous transforming growth factor beta1 stimulates endogenous transforming growth factor-beta1 mRNA expression approximately 8-fold. This effect depended on the concentration of extracellular type-II collagen. As the concentration of extracellular type-II collagen is increased, the expression of transforming growth factor-beta1 mRNA decreases in both basal and transforming growth factor-beta1-stimulated cultures. Exogenous extracellular type-I collagen also served to negatively modulate transforming growth factor-beta1 gene expression but with a different concentration profile. The results demonstrate that transforming growth factor-beta1 mRNA expression was upregulated by exogenous transforming growth factor-beta1 and was downregulated by extracellular type-I and type-II collagens. The profoundly different effects on transforming growth factor-beta1 expression by the two collagens are consistent with those reported for mammary epithelial cells and likely serve as a negative feedback mechanism to preserve tissue homeostasis. PMID- 11192254 TI - Osteoprogenitor cells within skeletal muscle. AB - The formation of ectopic bone within skeletal muscle is a widely observed phenomenon. However, the source of the osteoprogenitor cells responsible for ectopic bone formation remains unknown. This study was designed to test for osteogenic differentiation among cells isolated from skeletal muscle tissue. Different subpopulations of cells derived from an adult mouse skeletal muscle were tested for induction of alkaline phosphatase activity after exposure to bone morphogenetic protein-2 in vitro. A responsive subpopulation was identified, transduced with a retrovirus encoding for beta-galactosidase (Rv-lacZ) and an adenoviral construct encoding for one bone morphogenetic protein-2, and injected into the hindlimb of immune compromised (severe combined immunodeficient, or SCID) mice. The injected cells appeared to actively participate in the ectopic bone formation. The existence of lacZ-positive muscle-derived cells colocalized with osteocalcin-producing cells within lacunae of newly formed bone matrix suggests osteoblast and osteocyte differentiation. Although a specific cell was not isolated, these data support the contentions that osteoprogenitor cells reside within skeletal muscle and that muscle may represent a source other than bone marrow for the harvest of these cells. PMID- 11192255 TI - Is the circumferential tensile modulus within a human medial meniscus affected by the test sample location and cross-sectional area? AB - Quantifying the material properties of the human menisci is paramount to understanding their biomechanical functions within the knee. One important intrinsic material property governing the biomechanical functions of the meniscus is the circumferential tensile modulus. The purpose of this study was to determine if the circumferential tensile modulus of the human medial meniscus depends on the location and thickness of the sample tested. The following three hypotheses were tested: (a) the circumferential location (anterior, central, and posterior) does not significantly affect the tensile modulus, (b) the radial location (inner to outer) significantly affects the tensile modulus, and (c) the thickness (cross-sectional area) significantly affects the tensile modulus. Test samples, whose length was oriented in parallel with the circumferential collagen fibers, were collected from different circumferential and radial locations throughout 30 human medial menisci. Samples of three different thicknesses (0.5, 1.5, and 3.0 mm) were taken from three equal groups of 10 menisci (i.e., one thickness per group). The circumferential tensile modulus was measured under quasi-static loading. Statistical analysis showed no significant effect of the circumferential or radial location of the sample on the circumferential tensile modulus. This indicates that an overall circumferential tensile modulus may be calculated for the human medial meniscus by averaging the values determined at the various locations. However, the thickness of the test sample had a significant effect on the measured circumferential tensile modulus; the modulus varied inversely with the thickness. Thus, moduli determined from test samples that are too small in cross-sectional area overestimate the effective modulus of the tissue on the whole, and the cross-sectional area of the sample must be considered when determining a representative circumferential tensile modulus for the medial meniscus in a human knee. PMID- 11192256 TI - Tendon-Defect and muscle-unloaded models for relating a rotator cuff tear to glenohumeral stability. AB - Rotator cuff tear and glenohumeral instability are closely related. Any tear may disturb muscle force generation due to pain inhibition. In addition, a full thickness tear may foster instability by removing a structural element constraining the joint. It was hypothesized that the loss of both dynamic force and static constraint with a rotator cuff tear will affect glenohumeral stability. In a tendon-defect model, dynamic and static elements of the joint were sacrificed. In a muscle-unloaded model, only the dynamic element was removed. The location and size of the defect were also investigated. The effect on instability of a small tendon defect was less than that of muscle unloading, implying that a patient with a small tear would have less instability than a patient with weak or nonfunctioning supraspinatus and infraspinatus muscles. On the other hand, with a larger tear the defect had a greater effect than muscle unloading because sectioning of the glenohumeral and coracohumeral ligaments was included in the model. Clinically, such a defect in the front is critical for anterior stability because it might insult the important anterior capsule ligamentous complex. Orthopaedic surgeons should pay attention, therefore, to the effect of possible associated lesions of static constraints based on the size and location of the tear in addition to the dynamic stabilizer. PMID- 11192257 TI - Murine model for skeletal metastases of Ewing's sarcoma. AB - Ewing's sarcoma shows a strong tendency to metastasize to the lungs or the skeleton, or both. A peculiar feature of the secondary involvement of bone with this tumor is that it may also appear in the absence of clinically evident lung metastases, both at clinical presentation and during the course of the disease. Although osseous metastases are critically relevant for prognosis, the pathogenesis of this peculiar feature of Ewing's sarcoma is poorly understood, partly due to the lack of appropriate experimental in vivo models. We show that the intravenous injection of TC-71 Ewing's sarcoma cells into athymic 4-5-week old Crl/nu/nu (CD1) BR mice reproducibly colonizes specific sites of the skeleton in addition to the lungs and lymph nodes. The distribution and the morphologic appearance of these experimental bone metastases mimic the pattern of skeletal involvement observed in humans. This experimental model of bone metastasis of Ewing's sarcoma may be the basis for future studies aimed at understanding the pathophysiology and treatment of Ewing's sarcoma. PMID- 11192258 TI - Osteoprotegerin inhibits tumor-induced osteoclastogenesis and bone tumor growth in osteopetrotic mice. AB - Osteoprotegerin and osteoprotegerin ligand have recently been identified as novel proteins that inhibit and stimulate, respectively, osteoclast formation. We examined the possibility that osteoprotegerin would inhibit cancer-induced osteoclastogenesis and cancer growth in bone. An experimental model was used in which osteolytic tumors are known to stimulate osteoclastogenesis and grow in femora of osteoclast-deficient mice (op/op). Osteoprotegerin treatment decreased the number of osteoclasts by 90% (p < 0.0007) at sites of tumor in a dose dependent manner and decreased bone tumor area by greater than 90% (p < 0.003). The mechanisms through which osteoprotegerin decreased osteoclast formation in tumor-bearing animals included (a) an osteoprotegerin-mediated, systemic reduction in the number of splenic and bone marrow-residing osteoclast precursor cells, (b) a decrease in the number of osteoclast precursor cells at sites of tumor as detected by cathepsin K and receptor activator of NFkappaB mRNA expression, and (c) a decrease in osteoprotegerin ligand mRNA at sites of tumor. These findings suggest that osteoprotegerin treatment, in addition to having direct antagonistic effects on endogenous osteoprotegerin ligand, decreases the number of osteoclast precursors and reduces production of osteoprotegerin ligand at sites of osteolytic tumor. PMID- 11192259 TI - Cyclooxygenase-2 inhibitor SC-236 attenuates mechanical allodynia following nerve root injury in rats. AB - Low back pain is a common problem, affecting approximately two-thirds of the adult population. Of these individuals, a significant percentage will exhibit symptoms of radicular pain or sciatica. The purpose of this study was to determine the effect of one systemic (2 mg/kg) or intrathecal (0.2 mg/kg) dose of a selective cyclooxygenase-2 inhibitor (SC-236) in decreasing existing mechanical allodynia in a rat model of radiculopathy. Gait disturbance and mechanical allodynia (increased response to non-noxious von Frey monofilament stimuli) were assessed daily until the rats were killed 7 days after surgery. Robust mechanical allodynia developed in the rats in all groups except for those in the sham group by day 1 after surgery. Mechanical allodynia was significantly lower in the rats that received the systemic or the intrathecal dose of SC-236 than in those in the vehicle control group (analysis of variance followed by Bonferroni multiple comparison test, p = 0.002). The intrathecal drug route of administration produced greater attenuation in allodynia than the systemic dose, supporting a central mechanism of action of the cyclooxygenase-2 inhibitor (p = 0.002). The hypothesis that cyclooxygenase-2 is involved in spinal nociceptive processing after a nerve root injury was supported by this study. In addition, these data support continued basic science research to further elucidate central inflammatory processes that follow nerve root injury. PMID- 11192260 TI - Methylprednisolone reduces the early vascular permeability increase in spinal nerve roots induced by epidural nucleus pulposus application. AB - Autologous nucleus pulposus is known to have injurious effects on spinal nerve roots when applied epidurally. Both inflammatory and immunological mechanisms have been implicated in this regard. Various proinflammatory substances might be released or activated by nucleus pulposus and might affect the endoneural nerve root vessels. The present study assessed nucleus pulposus-induced early vascular reactions and the possibility of blocking these reactions with intravenous, high dose, methylprednisolone pretreatment. In 25 pigs, the S2 and S3 nerve roots were exposed. In five pigs (control group), retroperitoneal fat was applied epidurally on the nerve roots, and the other 20 pigs had nucleus pulposus applied. This group was sub-divided into the treatment group (n = 8), in which the pigs were pretreated with intravenous high-dose methylprednisolone (30 mg/kg body weight), and the nontreatment group (n = 12), in which the pigs received a corresponding volume of saline solution. After 2 hours, Evans blue labeled albumin was injected intravenously 5 minutes before death. Endoneural extravasation of Evans blue labeled albumin was evaluated with fluorescence microscopy. A marked albumin leakage was found in 67% of the nontreated animals, in 25% of those in the treatment group, and in none of the control animals. These results demonstrate that nucleus pulposus can induce a rapid increase in endoneural vascular permeability in spinal nerve roots after epidural application. This increase can be partially prevented by pretreatment with high-dose methylprednisolone. PMID- 11192261 TI - Reinsertion of stimulated nucleus pulposus cells retards intervertebral disc degeneration: an in vitro and in vivo experimental study. AB - Reinsertion of autogenous nucleus pulposus, an innovative method to delay further disc degeneration, has been proved with an experimental animal model. This study examined whether coculture of nucleus pulposus cells with annulus fibrosus cells (a) activates annulus fibrosus cells and (b) retards disc degeneration when reinserted into the disc in a rabbit model of disc degeneration. Coculture of the two cell types stimulated proliferation of each, as indicated by increased DNA synthesis measured by increases in DNA polymerase alpha expression and uptake of 5-bromo-2'deoxy-uridine assessed by an enzyme-linked immunosorbent assay. In a model of disc degeneration in rabbits, reinsertion of activated nucleus pulposus cells delayed the formation of clusters of chondrocyte-like cells, the destruction of disc architecture, and the elaboration of type-II collagen as measured immunohistochemically compared with no treatment. The direct reinsertion of activated nucleus pulposus cells into the disc offers a promising line of investigation for delaying intervertebral disc degeneration, although these results obtained with notochordal cells may not necessarily apply when mature central nucleus pulposus cells are used. PMID- 11192262 TI - Thermoregulation in Antarctic fulmarine petrels. AB - We measured resting metabolic rates at air temperatures between ca. -5 and 30 degrees C in snow petrels (Pagodroma nivea), cape petrels (Daption capense), Antarctic petrels (Thalassoica antarctica), and Antarctic fulmars (Fulmarus glacialoides). We measured seven age classes for each species: adults, and nestlings that were 3, 8, 15, 28, 35, and 42 days old. Basal metabolic rate (BMR) and thermal conductance (C) of adults averaged, respectively, 140% and 100% of values predicted allometrically for nonpasserine birds. Minimum metabolic rates of unfasted nestlings aged 15-42 days averaged, respectively, 97% and 98% of predicted adult BMR in Antarctic petrels and snow petrels, versus 119% and 126% of predicted in Antarctic fulmars and cape petrels. Nestlings of the southerly breeding snow petrel and Antarctic petrel were relatively well insulated compared with nestlings of other high-latitude seabirds. Adult lower critical temperature (T1c) was inversely related to body mass and averaged 9 degrees C lower than predicted allometrically. As nestlings grew, their T1c decreased with increasing body mass from ca. 14 to 22 degrees C (depending upon species) at 3 days of age, to -4 to 8 degrees C when nestlings attained peak mass. Nestling T1c subsequently increased as body mass decreased during pre-fledging weight recession. Nestling T1c was close to mean air temperature from the end of brooding until fledging in the three surface nesting species. PMID- 11192263 TI - Salt gland blood flow in the hatchling green turtle, Chelonia mydas. AB - Microsphere and morphometric techniques were used to investigate any circulatory changes that accompany secretion by the salt glands of hatchling Chelonia mydas. Salt glands were activated by a salt load of 27.0 mmol NaCl x kg body mass (BM)( 1), resulting in a mean sodium secretion rate of 4.14 +/- 0.11 mmol Na x kg BM( 1) x h(-1) for a single gland. Microsphere entrapment was approximately 160-180 times greater in the active salt gland than the inactive gland, inferring a similar change in blood flow through salt gland capillaries. The concentration of microspheres trapped in the salt gland was significantly correlated with the rate of tear production (ml x kg BM(-1) x h(-1)) and the total rate of sodium secretion (mmol Na x kg BM(-1) x h(-1)) but not with tear sodium concentration (mmol Na x l(-1)). Adrenaline (500 microg x kg BM(-1)) inhibited tear production within 2 min and reduced microsphere entrapment by approximately 95% compared with active glands. The volume of filled blood vessels increased from 0.03 +/- 0.01% of secretory lobe volume in inactive salt gland sections to 0.70 +/- 0.11% in active gland sections. The results demonstrate that capillary blood flow in the salt gland of C. mydas can regulate the activity of the gland as a whole. PMID- 11192264 TI - The absorption of calcium ions from the ovine reticulo-rumen. AB - Net Ca2+ and Mg2+ absorption rates were measured in vivo from buffer solutions placed in the washed reticulo-rumen, isolated in situ in 30 conscious, trained sheep. An increase in concentration of short chain fatty acids (SCFA) in the buffer, over the range 0-50 mM, was shown to stimulate the net rates of absorption of Ca2+ and Mg2+ ions from the rumen. Similarly, the results of in vitro experiments, carried out with ovine rumen epithelium mounted in short circuited Ussing chambers, showed that the absence of SCFA from the chamber fluid resulted in a reduction in Jnet Ca2+ caused by reduced flux of Ca2+ ions in the mucosal to serosal direction (Jms Ca2+). The addition of 1 mM acetazolamide, an inhibitor of carbonic anhydrase, to the ruminal buffer used in the in vivo experiments led to significant reductions in the net absorption rates of Ca2+ and Mg2+ ions in the presence of SCFA (50 mmol x l(-1)) but not in the absence of SCFA. However, in the in vitro experiments, the addition of 60 microM ethoxyzolamide had no significant effect on Jnet Ca2+. A reduction in pH of the intraruminal buffer in vivo from 6.8 to 5.4 led to significant increases in the net absorption rates of Ca2+ and Mg2+ ions, an effect which was duplicated for Ca2+ in preliminary in vitro experiments in which the pH of the mucosal buffer was reduced from 7.4 to 5.4. This stimulatory effect was confined to Jms Ca2+ and Jnet Ca2+. Ussing chambers were also used to demonstrate that Jnet Ca2+ was reduced by a high transmural potential difference (PD), caused by voltage clamping, independently of the mucosal K+ concentration. Both unidirectional Ca2+ fluxes consisted of a PD-dependent and a K+-insensitive PD-independent component. The latter may be represented by a Ca2+/ 2H+ antiporter. It is postulated that SCFA, and to a lesser extent H2CO3, can stimulate Jms Ca2+ by activation of an apical Ca2+/2H+ antiporter through the provision of protons within the ruminal epithelial cell. A mild reduction in ruminal pH may also lead to a similar stimulation of this putative electroneutral exchange. PMID- 11192265 TI - Selective stimulation and blockade of beta-adrenergic receptors in the mandibular gland of the red kangaroo, Macropus rufus. AB - Intracarotid infusions of noradrenaline (0.15 nmol x kg(-1) x min(-1)) either alone or accompanied by phentolamine (1.5 nmol x kg(-1) x min(-1)) caused similar sized increases in salivary protein, magnesium and bicarbonate, and decreases in osmolality, sodium, potassium and chloride whereas intravenous noradrenaline stimulated much smaller responses. Concurrent infusions of the beta1-antagonist, CGP20712A, blocked these noradrenaline-induced changes in salivary composition more effectively than equimolar infusions of the beta2-antagonist, ICI118551, thereby confirming the presence of beta1-adrenoceptors. Intracarotid infusion of salbutamol at 0.15, 0.3 and 1.5 nmol x kg(-1) x min(-1) caused increasing but qualitatively similar changes in salivary composition, sodium excepted, to intracarotid noradrenaline with 0.3 nmol being most similar quantitatively. Intravenous infusion of salbutamol caused larger changes in salivary composition than equimolar intravenous noradrenaline thereby indicating that the response to salbutamol may, in part, be mediated by reflex increases in general sympathetic tone triggered by lowered blood pressure. Eliminating this hypotensive effect by concurrent intravenous and intracarotid infusions of beta1-(CGP or atenolol) and beta2-(ICII18551) antagonists with intracarotid salbutamol showed that IC1118551 was more potent than the beta1-antagonists thereby demonstrating the presence of beta2-receptors. It was concluded that the kangaroo mandibular has functional beta1- and beta2-adrenoceptor subtypes in both endpieces and excurrent ducts and that the duct system has two populations of cells, each expressing one receptor subtype. PMID- 11192266 TI - Galactan biosynthesis in snails: a comparative study of beta-(1--> 6) galactosyltransferases from Helix pomatia and Biomphalaria glabrata. AB - Adult snails synthesize in their albumen glands a polysaccharide which is composed exclusively of D- or D- and L-galactose (Gal) residues which are interglycosidically linked by 1 --> 3 and 1 --> 6 bonds. It is the only carbohydrate source for embryos and freshly hatched snails. Two galactosyltransferases are described in this study which are most likely involved in the biosynthesis of this polysaccharide. One identified in Helix pomatia acts on oligosaccharides and could be used to synthesize a tetrasaccharide when the branched trisaccharide D-Gal-beta-(1 --> 3)-[D-Galbeta-(1 --> 6)]-D-Galbeta-1 --> OMe was offered as acceptor. This enzyme, requiring Mg++-and Mn++-ions for activity, introduced a linear beta-(1 --> 6) linkage at the terminal non-reducing ends and was not detected in Biomphalaria glabrata. The other enzyme, which introduced beta-(1 --> 6) linkages at subterminal D-Gal residues, thus forming branching points in the polysaccharide, was found in H. pomatia, Arianta arbustorum and B. glabrata with comparable activities. With the enzyme preparation of H. pomatia, up to four D-Gal residues were introduced into vicinal positions, forming single-membered side chains, if a hexasaccharide with five linearly beta-(1 --> 3)-linked D-Gal residues was offered as a acceptor. The multiple-branched structure formed is typical for snail galactans, making this enzyme a prime candidate for the branching enzyme in galactan synthesis. The enzyme activity could be solubilized and purified by affinity chromatography. In SDS-polyacrylamide electrophoresis, the Helix-derived eluate displayed two bands (68, 37 kDa) and that of Biomphalaria five bands (68, 63, 17.5; 15; 13 kDa). The purified material showed only 8% of the total activity of the crude extracts, but it could be shown that a phosphatase present in the crude extract can degrade UDP formed in the transfer reaction and thus drive the reaction to completion. PMID- 11192267 TI - Osmotic and ionic hemolymph concentrations of bathyal and abyssal amphipods of Lake Baikal (Siberia) in relation to water depth. AB - We studied the adaptive variations of the hemolymph concentrations in relation to water depth and pressure using deep-dwelling amphipods from Lake Baikal. Hemolymph osmolality was determined in six bathyal and abyssal species immediately after capture when values come closest to the habitat concentrations. In three species, hemolymph osmolalities correlated positively with depth of capture. Prevalent ions in the hemolymph are sodium and chloride. Lactate, our indicator for capture stress, was highest after trawling (2-6 mM) and lowest after retrieval from cages (0-0.6 mM). Acclimation to different pressure was studied by exposing the specimens to different water depths over several days. Hemolymph concentrations did not change after acclimation to surface pressure in the sublittoral Acanthogammarus albus, a native also to shallow water, but decreased by 30-80 mosmol/kg H2O in the bathyal and abyssal species Acanthogammarus grewingki, Acanthogammarus reicherti, and Parapallasea lagowskii. Similarly, hemolymph osmolality decreased in A. reicherti and P. lagowskii originating from deep water, when acclimated to reduced water depth, and, in A. reicherti hemolymph osmolality reached its original high value when returned to the depth of capture. Higher hemolymph osmolalities and NaCl concentrations, demonstrated here for the first time, may provide selective advantages to abyssal species. PMID- 11192268 TI - The autumnal fattening of the long-distance migratory garden warbler (Sylvia borin) is stimulated by intermittent fasting. AB - To investigate the proximate influence of a changing food availability on the seasonal fattening of migratory birds, garden warblers (Sylvia borin) following postnuptial moult were food restricted once a week. Body mass, food intake, plasma hormone and metabolite levels were measured and compared to birds which always had ad libitum food access. The food-restricted birds increased their body mass significantly earlier than the controls. The accelerated fattening was initially not accompanied by hyperphagia and may be due to either an increased food utilisation efficiency or a reduced metabolic rate. An increase of basal glucagon and corticosterone and a decrease of insulin levels prior to fattening were not significant, however, they resulted in a significant decrease of the insulin:glucagon ratio. This ratio was also lower in food-restricted birds than in control birds and may account for the difference in the fattening progress. We conclude that seasonal fattening may be stimulated by a catabolic impulse which could be imposed in free-living birds by a decrease of food availability and/or by an increase of energy expenditure. A negative energy balance is hypothesised to be a common proximate factor affecting migratory as well as winter fattening. PMID- 11192269 TI - Daily energy expenditure of the grey mouse lemur (Microcebus murinus): a small primate that uses torpor. AB - We aimed to investigate the pattern of utilisation of torpor and its impact on energy budgets in free-living grey mouse lemurs (Microcebus murinus), a small nocturnal primate endemic to Madagascar. We measured daily energy expenditure (DEE) and water turnover using doubly labelled water, and we used temperature sensitive radio collars to measure skin temperature (Tsk) and home range. Our results showed that male and female mouse lemurs in the wild enter torpor spontaneously over a wide range of ambient temperatures (Ta) during the dry season, but not during the rainy season. Mouse lemurs remained torpid between 1.7 8.9 h with a daily mean of 3.4 h, and their Tsk s fell to a minimum of 18.8 degrees C. Mean home ranges of mouse lemurs which remained normothermic were similar in the rainy and dry season. During the dry season, the mean home range of mouse lemurs showing daily torpor was significantly smaller than that of animals remaining normothermic. The DEE of M. murinus remaining normothermic in the rainy season (122 +/- 65.4 kJ x day(-1)) was about the same of that of normothermic mouse lemurs in the dry season (115.5 +/- 27.3 kJ x day(-1)). During the dry season, the mean DEE of M. murinus that utilised daily torpor was 103.4 +/- 32.7 kJ x day(-1) which is not significantly different from the mean DEE of animals remaining normothermic. We found that the DEE of mouse lemurs using daily torpor was significantly correlated with the mean temperature difference between Tsk and Ta (r2 = 0.37) and with torpor bout length (r2 = 0.46), while none of these factors explained significant amounts of variation in the DEE of the mouse lemurs remaining normothermic. The mean water flux rate of mouse lemurs using daily torpor (13.0 +/- 4.1 ml x day(-1)) was significantly lower than that of mouse lemurs remaining normothermic (19.4 +/- 3.8 ml x day(-1)), suggesting the lemurs conserve water by entering torpor. Thus, this first study on the energy budget of free-ranging M. murinus demonstrates that torpor may not only reflect its impact on the daily energy demands, but involve wider adaptive implications such as water requirements. PMID- 11192270 TI - On health inequality. PMID- 11192271 TI - Births, gestation and birthweights in South Tees 1990-1996. AB - BACKGROUND: The UK government has specified that all health authorities are to develop local health improvement programmes. Birthweight and gestational age are important health determinants, and therefore indicators of the health status of children in a community. They also have important resource implications for health and social services. Data regarding birthweight and its relationship to gestational age are not routinely available. This paper describes the results of the measurement of the birthweights and gestational ages of children born to residents in a UK health district, and their relationship with deprivation. METHODS: Routinely collected birthweight and gestational age data for children born to parents resident in the South Tees district during the period 1990-1996 inclusive were downloaded from the community child health department mainframe computer. The data were analysed and compared with national standards. RESULTS: The analysis showed that, despite the high levels of deprivation, birthweights were close to or slightly above average for most gestational ages. However, when compared with the average district in England and Wales, 8 per cent more low birthweight children, of which 42 per cent were less than 28 weeks gestation, were born in the area. Materially deprived mothers were more likely to give birth to pre-term and light for gestational age infants. CONCLUSIONS: This study has shown that it is now possible to use routine sources of information to monitor local trends in birthweight and gestation, and their relationship with deprivation. PMID- 11192272 TI - An audit of clinical nurse practitioner led thrombolysis to improve the treatment of acute myocardial infarction. AB - BACKGROUND: The aim of the study was to audit the impact of cardiac nurse practitioner led thrombolysis as a method of reducing call to needle times for acute myocardial infarction (AMI) in a single district hospital. METHODS: This was a prospectively planned, observational study, comparing time delay between arrival at hospital and the administration of thrombolysis ('door to needle' time) in patients presenting with AMI in a district general hospital serving a population of 270000. The 6 months before and 6 months after initiation of the scheme were compared. RESULTS: There were 151 consecutive patients (undergoing 163 thrombolysis episodes). The median door to needle time fell from 60 min (range 42-110 min) to 30 min (range 20-61 min) (p<0.01). In those patients eligible for immediate thrombolysis the number of cases treated within 30 min of arrival rose from 10/58 (17 per cent) to 48/64 (75 per cent) (p<0.01). The proportion of cases where there was an initial delay as a result of non diagnostic ECG or possible contra-indication to therapy remained constant, 20/78 (25 per cent) cases before and 21/85 (25 per cent) cases after initiation of the scheme. The number of cases of inappropriate thrombolysis fell from 73 per cent to 30 per cent. CONCLUSION: The provision of i.v. thrombolysis by cardiac nurse practitioners is safe and should be considered as a method for achieving acceptable door to needle times in the management of acute myocardial infarction. PMID- 11192273 TI - An audit of current clinical practice in the management of osteoporosis in Nottingham. AB - BACKGROUND: Osteoporosis is now recognized by the World Health Organization and the Department of Health as a major public health problem. In 1994, the Advisory Group on Osteoporosis (AGO), set up by the Department of Health, recommended that Health Authorities and general practitioner fundholders should purchase bone densitometry services for the management of osteoporosis. The aims of this study were to assess the criteria for requests for bone densitometry from primary care in comparison with the AGO recommendations and to compare the numbers of patients referred with a low-trauma osteoporotic fracture with the expected number of fractures in the Nottingham area. METHODS: Patient referral data and requests for bone densitometry were collected by case note review of all new patients referred to the Nottingham Osteoporosis Clinic over a 12 month period and then compared with the AGO recommendations. The patients referred with a history of a low trauma fracture were then compared with the expected incidence of fractures, calculated using age-sex-specific fracture incidence data applied to the Nottingham population Census statistics. RESULTS: A total of 413 patients were referred to the Osteoporosis Clinic for bone densitometry. Almost two-thirds of the patients had no clinical indicators for requests for scanning, in comparison with the AGO recommendations. Seventy-seven patients were referred with vertebral fracture, 12 hip, 20 colles and 26 other fractures. Using age-sex-specific fracture incidence data applied to the Nottingham population Census statistics, it was estimated that the expected incidence of hip fractures would be 812, distal forearm fractures 514 and vertebral fractures presenting to clinical attention 625. This represents 1.5 per cent of the total hip fractures, 3.9 per cent distal forearm and 12.3 per cent vertebral actually presenting to the Osteoporosis Clinic. CONCLUSION: Bone densitometry was requested in up to 60 per cent of the patients with no clinical risk factors to warrant bone densitometry. Osteoporosis-related fractures remain unrecognized in clinical practice. The majority of patients do not receive specialist assessment despite being at high risk of future fracture. Further steps are necessary to educate health care professionals in primary and secondary care, but more importantly, to direct services more proactively in those at high risk of future fracture. PMID- 11192274 TI - Assessment of parents' concerns and evaluation of outcomes. AB - BACKGROUND: Clinical and service evaluation often fails to accommodate sufficiently to parental perspectives and priorities concerning health interventions. Although parent satisfaction questionnaires are widely used, these assess issues chosen by the researcher. Quality of life research methods, however, can assess individual priorities. METHODS: A Schedule for Evaluation of Quality of Life was adapted to record the nature, and relative importance of parental concerns about their child before child psychiatric hospital admission. Level of concern or worry was assessed pre- and post-admission, and at 1 year follow-up, with a waiting-list control. Data were analysed qualitatively and quantitatively for individuals and groups of cases. RESULTS: The adapted instrument was feasible and clinically useful. It did not show repeated measurement effects but was sensitive to the effects of intervention (hospital admission). Effects (reduction in levels of concern) remained evident at 1 year follow-up. CONCLUSION: The instrument is brief, non-intrusive, and sensitive to change. It has utility for clinical case evaluation. It may complement satisfaction questionnaires, and has advantages over rating scales for the evaluation of treatment outcomes. PMID- 11192275 TI - Twenty year follow-up of a cohort based in general practices in 24 British towns. AB - BACKGROUND: A national prospective study of cardiovascular disease (CVD) was set up in 1978 to explain the reasons for the marked geographical variation in CVD rates in Great Britain. A total of 7735 males, aged 40-59 years (born between 1919 and 1939) randomly selected from one general practice age-sex register in each of 24 towns, responded to a screening invitation from their general practitioner (GP) and were examined in 1978-1980. We describe the methods used and the contact maintained after following a cohort for 20 years. METHODS: The established system of patient registration with a GP was used for tracing and maintaining contact with a low-mobility cohort through local area health authority networks and the National Health Service Central Register. RESULTS: By 31 December 1997, there were 1856 recorded deaths (14 known to have occurred abroad), 66 emigrations/ living overseas/lost from follow-up. In addition, 1500 study subjects had registered with new GPs who, every 2 years, provided information on both fatal and non-fatal cardiovascular events to complement information supplied by the original practices. Information was obtained on all cardiovascular events and deaths for 99.5 per cent of the surviving sample. Questionnaires mailed to surviving subjects 5 years after recruitment (1983-1985) and again in November 1992 and 1996 were returned by 98, 90 and 88 per cent, respectively, providing information on lifestyle changes, new cardiovascular symptoms and new diagnoses. CONCLUSION: Using the NHSCR framework for primary care registration procedures, maximum follow-up has been maintained. Brief and structured enquiry forms have gained and maintained co-operation from subjects and their GPs with considerable success. Mortality reporting from dual sources identified 5 per cent more cases. PMID- 11192276 TI - Democratic prioritization of maternity care: a rational basis for planning a clinical effectiveness programme. AB - BACKGROUND: The aim of the study was to evaluate the use of a democratic process for prioritizing the ASQUAM (Achieving Sustainable Quality in Maternity) clinical effectiveness programme. METHODS: Twenty-two improvements in the standards of maternity care were chosen as top-topic priorities at the 1996 and 1997 ASQUAM meetings. We wished to assess the relative priorities of local and national delegates, by comparing their voting patterns at the two meetings. The setting was North Staffordshire ASQUAM prioritization days, and the subjects were all the delegates at the 1996 and 1997 ASQUAM meetings. Main outcome measures were comparison of numbers of votes cast by local and national delegates for each of the 20 topics presented at the two ASQUAM meetings, and proportions of the 11 top topics decided at each meeting that were chosen by local and national delegates. RESULTS: In 1996, significantly more local than national delegates voted for two topics related to maternal mortality or morbidity (incontinence and hypertensive diseases of pregnancy), but there were no statistically significant differences between the proportions of votes cast for any of the other 18 topics presented on the day. Indeed, local delegates had prioritized 11/11 of the final top-topics, and only one was omitted by the national delegates (10/11). In 1997, significantly more national than local delegates voted for three topics relating to professional stress levels, user involvement in working groups and antibiotic prophylaxis, but there were no statistically significant differences between the proportions of votes cast for any of the other 17 topics presented on the day. Again, local delegates had prioritized 11/11 of the final topics, with only one being omitted by the national delegates (10/11). CONCLUSION: There appeared to be a remarkable concordance between local and national delegates at both meetings, suggesting an underlying rationality to decision making. We believe this to be a reflection of the process of careful evaluation of outcome and intervention supported by the protection of a secret ballot, allowing free expression of individual's values. PMID- 11192277 TI - The health of students in institutes of higher education: an important and neglected public health problem? AB - BACKGROUND: A survey of students in three UK higher education establishments was undertaken to obtain information about students' physical and emotional well being, their attitudes to, and beliefs about health, and the prevalence of risk factors for future ill health. METHODS: Health was measured by the prevalence of longstanding illness and by the SF-36 health status measurement tool. Survey results were compared with equivalent data for 18- to 34-year-olds in the local population. The prevalence of long-standing illness was also compared with two national surveys. RESULTS: The survey achieved a 49 per cent response rate. More than one-third of respondents reported a long-standing illness, a higher prevalence than in all comparison surveys. Students scored significantly worse than their peers in the local population on all eight SF-36 dimensions. The greatest difference was for role limitations as a result of emotional problems. The main sources of emotional distress were study or work problems and money. CONCLUSION: The poor response rate in this survey dictates the need for caution in interpretation of the results. However, they suggest that the health of students is poor relative to that of their peers, and that their emotional health is more of a problem than their physical health. Public health practitioners might want to pay more attention to the health of this important and relatively neglected group. Worries about studies and money appear to be affecting students' academic work, and this should be of concern to higher education establishments. PMID- 11192278 TI - The effects of neonatal screening for sickle cell disorders on lifetime treatment costs and early deaths avoided: a modelling approach. AB - BACKGROUND: The aim of the study was to calculate the cost to the UK National Health Service of providing treatment services for patients with sickle cell disorders. The rates of differential morbidity and mortality, in the first 10 years of life, between screen-detected early diagnosed and clinically presenting late diagnosed cohorts of sickle cell disorder patients are also estimated. METHOD: A cost model was developed, based on predictions of survival and the incidence of sickle cell disorder-related events. Direct data from the NHS are lacking, so data were incorporated from disparate sources. Patients with sickle cell disorders were divided into two categories: those with sickle cell anaemia and those with sickle HbC disease. RESULTS: Differentiating between sickle cell anaemia and sickle HbC disorder patients, the results show that the undiscounted (discounted at 6 per cent) lifetime treatment costs range from pound sterling 92323 (pound sterling 24917) to pound sterling 185614 (pound sterling 53861). The number of early deaths avoided per 100 births, as a result of early diagnosis through screening, ranges from 0.57 to 1.25. CONCLUSIONS: The resulting estimates may act as a guide to those involved in the planning of health care provision with regard to the resources required to treat sickle cell disorder patients. Such information may also be incorporated into the evaluation of both antenatal and neonatal screening programmes for sickle cell disorders. PMID- 11192279 TI - Effective management of the elderly hearing impaired--a review. AB - In the United Kingdom, two and a half million people over 70 are thought to have hearing impairment that would benefit from an aid. Only one-third of these will possess one, and as many as 10 per cent probably never use their aid. Although it is important to examine the relative merits of different aids, there is also a need to look at how audiological services may reduce the unmet need that results from underuse of aids. This review examines the important question of 'what is the most effective way of providing hearing aids for the elderly affected by presbyacusis?' Extensive searching of four electronic databases and hand searching of relevant journals revealed the paucity of evidence to guide audiology practice. In particular there is little consensus on the best outcome measures for evaluating audiological rehabilitation or hearing aid fitting. Audiological services for the elderly are another example of an area where there is a need to fund research and development rather than continue to commission services that are variable and poorly evaluated. PMID- 11192280 TI - The Global Burden of Disease Study: a useful projection of future global health? AB - One major conclusion of the Global Burden of Disease Study (GBDS) is that the global burden of disease will not change significantly from 1990 to 2020, in developed regions, developing regions or as a whole. Using the disability adjusted life year (DALY), the Study estimates the burden as a result of 107 diseases, accidents and their disabling sequelae, disaggregated with respect to cause, sex, age and geographical region. The basic data used to construct estimates are sparse, and the DALY as a tool has received many criticisms. It obscures the distribution of disease and its impact in terms of handicap, and includes several social and economic value judgements. This weakens its power as a guide for the rational allocation of health resources at any point in time. Does it have use in guiding future planning and preventive action? At a global level, exceeding ecological capacity primarily through relative overpopulation is likely to be the greatest threat to overall health, yet overpopulation is not considered as a risk factor in itself. This reflects the understanding of health as an issue of the individual rather than the community. Together with the productivity-orientated weighting of DALYs, the Study appears to be more concerned with cost-effectiveness of health interventions rather than their equity. This underlies the reservations of the World Health Organization regarding the Study's use as a rational tool in health policy. PMID- 11192281 TI - Contamination of allotment soil with lead: managing potential risks to health. AB - BACKGROUND: In the context of contaminated land, assessing risk involves identifying a source, a pathway and a receptor. We describe how this approach worked in practice following the discovery of high lead levels in the soil of an allotment site in a London borough. METHODS: Soil and produce analyses were undertaken. A worst-case scenario was constructed to estimate the maximum potential lead intake by consumers. A questionnaire survey was undertaken of individuals who either worked on the allotment or ate significant amounts of produce grown on it. They were also offered blood lead tests. RESULTS: High lead levels were found in soil and produce. The worst-case assessment showed that the estimated lead intake by a hypothetical consumer of allotment produce exceeded the provisional tolerable weekly intake almost 10-fold. Further tests on produce indicated that soil contamination had contributed to the high lead levels. The questionnaire survey did not reveal any chronic illness related to lead exposure. Of the five tested, none had raised blood lead levels. CONCLUSIONS: A decision was made to remediate the site. Pending this, we advised the allotment holders not to cultivate the land or eat any produce grown on it as we could not be sure that preparation of the produce before consumption would remove all adherent lead contaminated soil, and continued cultivation could also expose them to lead in the soil dust. PMID- 11192282 TI - Screening for HIV, HBV and HCV markers among drug users in treatment in rural south-east England. AB - BACKGROUND: This study was designed as an opportunistic screening to estimate the prevalence of blood-borne viral infection among drug users in treatment in the rural population and to investigate related risk factors and use of general health services. METHODS: A total of 102 patients aged 18 years and over (78 male, 24 female) with problematic self-reported drug use, recruited between 1 February 1996 and 31 January 1997, in a mixed urban-rural population in south east England, were interviewed for information on socio-demographic status, drug use history, HIV-related risk behaviours, hepatitis B vaccination, general practice consultations, and use of A&E departments and medical out-patient clinics. Diagnostic testing was offered to all patients for anti-HIV-1, anti-HBc, HBsAg and anti-HCV. RESULTS: The mean age at onset of illicit drug use for the entire sample was 15.33 (SD 3.36) years; 3.7 per cent (1/27), 20.4 per cent (18/88), and 55.8 per cent (48/86) had antibodies to HIV-1, HBc and HCV, respectively; 1.1 per cent (1/88) tested positive for HBsAg indicative of a carrier state. All 18 patients anti-HBc seropositive were male (p = 0.009). There was no gender difference for anti-HCV serological status. The proportion of town residents and village dwellers seropositive for anti-HBc and anti-HCV did not differ significantly. Patient's age at interview, age at onset of opioid use and duration of opioid use showed a significant association with anti-HBc and anti HCV serological status. The proportion directly sharing injecting equipment was too small for rigorous statistical analysis; however, indirect sharing involving cooking equipment and frontloading rituals achieved statistical significance. Anti-HBc serological status showed a significant association with vaginal intercourse without a condom (p = 0.03); none of the sexual risk behaviour variables revealed any significant association with HCV infection. Although only one-third of the sample consented to HIV antibody test, consenting and non consenting groups did not differ significantly except on one variable: having a drug-using sexual partner (chi2 = 5.6167; p = 0.017). Serum aspartate amino transferase and gamma-glutamyl transpeptidase concentrations were raised above the upper limit in 23 (25.7 per cent) of the 89 patients who gave blood specimens; 41.2 per cent (42/102) were referred to treatment by their general practitioners. There was no significant relationship between HBV and HCV serological status and general practice consultations. Only eight (7.8 per cent) had received hepatitis B vaccination, and although 48 (47.1 per cent) had in the preceding 12 months used A&E departments, only seven (6.2 per cent) had been seen in medical out-patient clinics. CONCLUSION: In this study the prevalence of HIV, HBV and HCV in the rural population is as high as has been reported for inner cities. The poor uptake of hepatitis B vaccination among drug users, their poor response to HIV antibody test and poor health service utilization suggest the need for an urgent appraisal of service provision and a review of prevention and treatment strategies. PMID- 11192283 TI - STDs aren't sexy: health professionals' lack of adherence to clinical guidelines in an area of high STD endemicity. AB - BACKGROUND: In 1997 the Health Department of Western Australia distributed clinical guidelines aimed at improving the outcomes of care of patients with STDs. In recognition of the high STD rates and issues peculiar to the Kimberley region, a Kimberley Supplement was inserted into copies distributed in the region. Since then, annual STD workshops have been conducted for all Kimberley health professionals involved in any aspect of STD management. This study aimed to assess whether health professionals were observing the Guidelines and its Kimberley Supplement, and whether adherence improved after the 1998 Kimberley STD workshop tour. METHODS: Over two periods, pre- and post-STD workshops, all pathology request forms for gonorrhoea and chlamydia tests were collected from all laboratories in the region. The outcomes of interest were which of the recommended tests had been requested. Logistic regression was used to analyse associations between adherence to the Guidelines and patient's age, sex and postcode, profession of practitioner, reason for testing and whether the test was performed pre- or post-STD workshops. RESULTS: Minimum appropriate tests were ordered on only 14.5 per cent (98/676) of request forms. Univariate and multivariate analyses showed that minimum appropriate testing was more likely to have been requested on male patients and if the practitioner was a doctor. No improvement was observed after the STD workshops. CONCLUSION: The poor adherence and lack of improvement observed can be explained by Kotter's framework on why transformation efforts fail. This study demonstrates that clinical guidelines are of little value unless they are continuously evaluated. PMID- 11192284 TI - Quarterly communicable disease review: April to June 2000--from the PHLS Communicable Disease Surveillance Centre. PMID- 11192285 TI - Pollution from chrome waste. PMID- 11192286 TI - A live attenuated West Nile virus strain as a potential veterinary vaccine. AB - This article reviews the development of two attenuated West Nile virus (WNV) variants, WNI-25 and WNI-25A. These variants have lost the neuroinvasion trait of the parental virus. Attenuation was achieved through serial passages in mosquito cells and neutralization escape from WNV-specific monoclonal antibody. Genetic analysis reveals amino acid changes between the parental and each of the variants. The attenuated variants preserve the ability to replicate in mice and geese and to induce a protective immune response. WNI-25A was found to be a genetically stable virus. This variant was successfully used as a live vaccine to protect geese against a wild-type virulent WNV field isolate that closely resembles the WNV isolated during the 1999 New York epidemic. PMID- 11192287 TI - West Nile virus in the New World: appearance, persistence, and adaptation to a new econiche--an opportunity taken. PMID- 11192288 TI - European experience with the West Nile virus ecology and epidemiology: could it be relevant for the New World? AB - A review of West Nile virus (WNV) and the epidemiology of West Nile fever (WNF) in Europe is presented. European epidemics of WNF reveal some general features. They usually burst out with full strength in the first year, but few cases are observed in the consecutive 1 to 2 (exceptionally 3) years, whereas smaller epidemics or clusters of cases only last for one season. The outbreaks are associated with high populations of mosquitoes (especially Culex spp.) caused by flooding and subsequent dry and warm weather, or formation of suitable larval breeding habitats. Urban WNF outbreaks associated with Culex pipiens biotype molestus are dangerous. Natural (exoanthropic, sylvatic) foci of WNV characterized by the wild bird-ornithophilic mosquito cycle probably occur in many wetlands of climatically warm and some temperate parts of Europe; these foci remain silent but could activate under circumstances supporting an enhanced virus circulation due to appropriate abiotic (weather) and biotic (increased populations of vector mosquitoes and susceptible avian hosts) factors. It is very probable that WNV strains are transported between sub-Saharan Africa and Europe by migratory birds. The surveillance system for WNF should consist of four main components: (1) monitoring of mosquito populations and their infection rate; (2) wild vertebrate surveys; (3) sentinel birds (domestic ducks rather than chickens); and (4) monitoring of human disease. In the case of persisting high risk of WNF for humans and equids in certain enzootic areas, immunization against WNF should be considered. For that purpose a commercially available, cross protective vaccine against Japanese encephalitis could be used. PMID- 11192289 TI - West Nile virus investigations in South Moravia, Czechland. AB - Seven virus isolates were obtained from 11,334 mosquitoes after the 1997 Morava River flooding in South Moravia (Czech Republic): 6 strains of Tahyna bunyavirus, California antigenic group (5 from Aedes vexans, 1 from Ae. cinereus), and 1 strain of West Nile flavivirus (WNV) from Culex pipiens. In 1999, one isolate of Tahyna virus from Ae. vexans and one isolate of WNV from Cx. pipiens were recovered from a total of 14,354 mosquitoes examined in the same area, whereas no virus was detected there in 1,179 overwintering mosquitoes (mostly Cx. pipiens) in March 2000. The infection rate of mosquitoes with arboviruses was significantly higher in 1997, the year of the flood and an enormously high population density of mosquitoes. Antibodies neutralizing WNV were detected in 13 of 619 (2.1%) hospitalized patients or persons seeking outpatient clinics of the area in 1997. Five of the seroreactors revealed clinical symptoms compatible with West Nile fever: in 2 of them (children), recent infection with WNV was confirmed by a significant increase of antibody titer between acute and convalescent serum samples. PMID- 11192290 TI - Discovery and molecular characterization of West Nile virus NY 1999. PMID- 11192291 TI - The emergence of West Nile virus: the Australian connection. PMID- 11192292 TI - West Nile virus in New York State: the 1999 outbreak and response plan for 2000. PMID- 11192293 TI - West Nile virus in the United States: guidelines for detection, prevention, and control. AB - The epidemic/epizootic of West Nile (WN) encephalitis in the northeastern United States in the summer and fall of 1999 was an unprecedented event, underscoring the ease with which emerging infectious pathogens can be introduced into new geographic areas in today's era of rapid transportation and increased movement of people, animals, and commodities. This epidemic/epizootic and the increased frequency of other exotic pathogens being imported into the United States raises the issue of whether local, state, and national public health agencies are prepared to deal with epidemics/epizootics of vector-borne infectious diseases. The overwintering of WN virus and the epizootic transmission in the summer of 2000 reinforces the need to rebuild the public health infrastructure to deal with vector-borne diseases in this country. This article summarizes guidelines for surveillance, prevention, and control of WN virus that were drafted in December 1999 to help prepare state and local health departments for monitoring WN virus activity in the spring and summer of 2000 and also summarizes the data collected from those surveillance systems through September 2000. PMID- 11192294 TI - Innate and acquired immunity at mucosal surfaces. PMID- 11192295 TI - CD8+ cell lines isolated from HIV-1-infected children have potent soluble HIV-1 inhibitory activity that differs from beta-chemokines. AB - CD8+ cells from human immunodeficiency virus type 1 (HIV-1) infected individuals have been shown to suppress HIV-1 replication both through a major histocompatibility complex (MHC)-restricted cytolytic pathway as well as through a noncytolytic pathway mediated through soluble factors. To characterize this soluble activity and its potential role in disease progression further, we studied the HIV-1 inhibition by supernatants derived from herpesvirus saimiri transformed CD8+ cells isolated from infected children. Three of the six CD8+ cell lines derived had a phenotype consistent with an unusual natural killer (NK) cells phenotype with low CD3, high CD56, and low CD16. Supernatants from some of the cell lines derived from children with rapid progression as well as long-term nonprogressors exhibited broad HIV-1-inhibitory activity in primary CD4+ cells as well as in primary macrophages. In contrast to a cocktail of beta-chemokines, the supernatants inhibited T-tropic as well as M-tropic viruses, efficiently inhibited infection in primary macrophages, and inhibited HIV-1 activation in the chronically infected U1 cell line. The HIV-1-inhibitory activity was heat stable and active over a broad pH range. Fractionation of the supernatant by size and ion exchange chromatography demonstrated activity in the complete absence of RANTES as well as interferons-alpha, beta, and gamma and in a size range of less than 10 kD and greater than 3 kD. CD8+ cell supernatants contain additional unidentified factors that have anti-HIV activity to account for this broad phenomenon. PMID- 11192296 TI - Altered prevalence and reactivity of anti-Epstein-Barr virus antibodies in patients with multiple sclerosis. AB - In this study, the prevalence and reactivity of anti-Epstein-Barr virus (EBV) antibodies were investigated in 107 patients with multiple sclerosis (MS) in comparison to age- and gender-matched healthy controls from a north German state. We found a significant 100% EBV-seropositivity and a significant lack of primary EBV infections in the MS group, indicating that all MS patients are infected with EBV before the development of MS. Although there were no differences in reactivities of EBV-specific anti-early antigen (EA)-immunoglobulin G (IgG), IgM, and -IgA antibodies between each group, MS patients had significant lower anti-Epstein-Barr nuclear antigen (EBNA)1-IgG antibody titers as a possible serological sign for a defective control of the persistent latent EBV carrier state and EBV reactivations. Longitudinal studies of MS patients are necessary to further determine the implications of EBV reactivations on the course and disease activity of MS. PMID- 11192297 TI - QS-21 synergizes with recombinant interleukin-12 to create a potent adjuvant formulation for the fusion protein of respiratory syncytial virus. AB - In the murine model of respiratory syncytial virus (RSV) infection, recombinant interleukin-12 (rIL-12) was previously demonstrated to be most effective as an adjuvant for fusion (F) protein-based vaccines after adsorption to alum adjuvant. Alum, however, is a potent inducer of polarized T-cell responses and the type 2 phenotype. In addition, studies in human cancer patients demonstrated that rIL-12 was toxic when administered systemically at high doses. Because of these issues, we investigated whether the saponin QS-21 could facilitate a reduction in dose of rIL-12 when F protein was prepared in the absence of alum (F/rIL-12). The results demonstrated that a suboptimal dose (0.8 microg) of QS-21 enhanced the capacity of F/rIL-2 to elicit antigen-dependent killer cell precursors and complement assisted neutralizing antibodies in spleens and sera respectively of BALB/c mice. The killer cell activity of mice vaccinated with F/rIL-12 (0.1 microg) plus 0.8 microg QS-21 was equivalent to that elicited after vaccination by experimental infection, or with an optimal dose of QS-21. The neutralizing titers generated by F/rIL-12 (0.01 to 1.0 microg) were also significantly elevated in the presence of 0.8 microg QS-21. Thus, rIL-12 and QS-21 together form a potent adjuvant for eliciting functional cell-mediated and humoral immune responses against F protein. PMID- 11192298 TI - Cytolytic function for pseudorabies virus-stimulated porcine CD4+ CD8dull+ lymphocytes. AB - We previously observed that pseudorabies (PRV) virus-specific killing in vitro was mediated by CD6+ CD8+ lymphocytes. Also a high percentage of CD4+ lymphocytes, among these CD6+ CD8+ lymphocytes, was observed. The purpose of this study was, therefore, to further characterize the killing ability of PRV stimulated CD4+ CD8+ lymphocytes. Peripheral blood mononuclear cells (PBMC) were isolated from blood of PRV-immune pigs and were stimulated in vitro with PRV. After 6 days, the frequency of CD4+ CD8+ lymphocytes in peripheral blood was determined by flow cytometry analyses. Lymphocytes were separated using a magnet activated cell sorter or a FACSVantage SE, and the cytolytic activity of the isolated populations was determined. Flow cytometry analyses demonstrated that PRV stimulation of immune PBMC resulted in the occurrence of 26% +/- 4% CD4+ CD8dull+ lymphocytes. We further demonstrated that killing by PRV-stimulated PBMC was mediated by CD4+ CD8dull+ T lymphocytes and CD4- CD8+ T lymphocytes (classic cytolytic T lymphocytes and natural killer cells). The CD4+ CD8dull+ T lymphocytes showed major histocompatibility complex (MHC) II-restricted PRV specific killing. The CD4- CD8+ T lymphocytes showed both PRV-specific and natural killing. The CD4+ CD8dull+ lymphocytes, which are unique in the pig, seemed to have a more heterogeneous function than was earlier demonstrated. In conclusion, we demonstrated that PRV-specific CD4+ CD8dull+ lymphocytes are able to kill PRV-infected target cells in a MHC II-restricted manner. PMID- 11192299 TI - Immunological responses in patients who have spontaneously eradicated hepatitis C virus infection. AB - We examined the proliferative responses of peripheral blood mononuclear cells obtained from 60 untreated patients who were seropositive by enzyme immunoassay, but negative for hepatitis C virus (HCV) RNA by reverse transcriptase-polymerase chain reaction (RT-PCR). We used second- and third-generation recombinant immunoblot assay (RIBA) for further serological characterization. In vitro HCV specific proliferative responses of mononuclear cells were compared to those of both untreated chronic HCV patients and patients who showed sustained virological response to interferon-alpha monotherapy, in order to assess the relative contribution of the immune response to the eradication of HCV. We found that frequency of responses to nonstructural proteins showed statistically significant differences, which were attributable to vigorous, polyspecific responses by cells from the RIBA-positive patients. In this group, core-specific proliferation was significantly associated with intravenous drug use as route of acquisition. Both other patient groups and the RIBA-indeterminate patients showed indistinguishable frequencies of proliferative responses. No association was detected between residual humoral responses, as determined from the RIBA results, and elapsed time since infection. The frequency of antibodies to NS5 differs between spontaneous cure and chronically infected patients. Cell-mediated and humoral immunity appear to be maintained in this population of patients. PMID- 11192300 TI - An immunodominant, cross-reactive B-cell epitope region is located at the C terminal part of the hamster polyomavirus major capsid protein VP1. AB - The VP1 represents the major capsid protein of the hamster polyomavirus (HaPV). Here we describe the mapping of epitopes along the VP1 using Escherichia coli expressed VP1-dihydrofolate reductase (DHFR) fusion proteins and PepScan analysis. By use of DHFR fusion proteins an immunodominant region was localized in the C-terminal part of VP1 between amino acids 320-384. Further epitopes are located in the regions amino acids 1-133 and amino acids 133-320, respectively. There were no obvious differences in the reactivity between sera of tumor-bearing and papilloma-free naturally HaPV-infected hamsters. In contrast, PepScan analysis revealed linear epitopes in the regions amino acids 79-97 and amino acids 353-367 for tumor-bearing animals and amino acids 101-113 and amino acids 165-179 for papilloma-free animals. The region between amino acids 320-384 of HaPV-VP1 was found to be involved in cross-reactivity of VP1 from HaPV and other polyomaviruses. Previously we have demonstrated that heterologous expression of HaPV-VP1 allowed the formation of virus-like particles (VLPs). From epitope mapping data and structural predictions it has been suggested that HaPV-VP1-VLPs may tolerate foreign peptides in the region amino acids 81-88 and the C-terminal part of VP1. PMID- 11192301 TI - Short synthetic peptides derived from viral proteins compete with HIV gp120 for the binding to CD4 receptors. AB - In the complex mechanism of adhesion, internalization, and infection of cells by human immunodeficiency virus (HIV) viral particles, a determinant role is played by the viral envelope glycoprotein gp120, which binds to CD4 receptors of T cells and monocytes. We tested the ability of a panel of 7- to 12-residue synthetic peptides, selected from the region 414-434 of the HIV-1 gp120, to inhibit the binding of the viral protein to CD4 receptors of cultured human lymphoid cells. The assay was based on the observation that the binding of gp120 to the receptors interferes with the binding of a specific anti-CD4 monoclonal antibody, as a result of the masking of the antibody epitope; thus, we tested whether preincubation of cells with the peptides before gp120 addition might restore the recognition of the CD4 molecule by the antibody. High expression of CD4 receptors was thus assumed as indication that the binding of the viral protein had been inhibited. Maximum activity was displayed by a 9-residue peptide located near the amino terminal end of the 414-434 fragment. In addition, several fragments deduced from other viral proteins, possessing partial amino acid sequence homology with the HIV gp120 fragment, exhibited a similar type of interaction with the CD4 receptor. All active peptides contain the Cys residue (position 423 of gp120). This residue is essential, although not sufficient, for inhibiting gp120 binding, as few other amino acid residues within the fragment play a complementary role in increasing or decreasing the inhibitory ability. PMID- 11192302 TI - Five-year clinical experience with Abiomed BVS 5000 as a ventricular assist device for cardiac failure. AB - Mechanical support for the failing heart has interested and challenged cardiac specialists for decades. In the United States alone, there are close to 375,000 cardiac surgical procedures performed each year, and, despite the recent advances in myocardial protection, surgical techniques, intra-aortic balloon therapy and maximal pharmacological support, postoperative ventricular dysfunction continues to occur in 0.5-1.0% of all patients undergoing cardiac surgery. This retrospective review describes our 5-year clinical experience at the Brigham and Women's Hospital with the Abiomed BVS 5000 as a means of ventricular support. During the period of 1994 to present, 7,428 cardiac surgical operations were performed at our institution. The Abiomed BVS 5000 has been implanted in 47 patients exhibiting ventricular failure. There were 38 patients in the bridge-to recovery group and nine patients in the bridge-to-transplantation group. Twenty five patients (66%) in the bridge-to-recovery group were weaned and 16 patients (42%) went on to discharge. In the bridge-to-transplantation group, one patient actually recovered myocardial function and one expired on the device. The remaining seven patients (77%) underwent cardiac transplantation with post transplant survival at 66%. Overall, patients were supported in the isolated left ventricular mode (28%), in the biventricular mode (45%) and in the isolated right ventricular mode (28%). The Abiomed BVS 5000 has been shown to be a safe and simple cardiac support system with no mechanical failure. Our experience shows that a substantial number of patients suffering from ventricular failure will benefit from the use of this device. The results also justify the use of this device in groups of patients other that of postcardiotomy ventricular failure. PMID- 11192303 TI - Significant reduction of air microbubbles with the dynamic bubble trap during cardiopulmonary bypass. AB - Air microbubbles mostly occur unnoticed during cardiopulmonary bypass and are predominantly responsible for serious postoperative psychoneurological dysfunction. A dynamic bubble trap (DBT), which removes air microbubbles from the arterial blood, was tested in a clinical study. The aim was to evaluate the efficiency of microbubble removal under clinical conditions. As blood passes through the DBT, which is placed in the arterial line between the arterial filter and arterial cannula, it is converted into a rotating stream. The bubbles are directed to the centre of the blood flow and are collected in the distal end of the DBT, from where they are returned to the cardiotomy reservoir. Doppler ultrasonography was used to detect the microbubbles before and after the DBT, and also the number of high-intensity transient signals (HITS) in the right and left middle cerebral artery during extracorporeal circulation. A significant reduction of microbubbles in the arterial line (3,990 before DBT, 537 after, p < 0.001) and HITS in the brain (51 in the DBT group, 77 in the placebo group, p = 0.04) was measured. PMID- 11192304 TI - Inflammo-coagulatory response, extrinsic pathway thrombin generation and a new theory of activated clotting time interpretation. AB - When blood is subjected to contact with foreign surfaces, as during cardiopulmonary bypass (CPB), the whole body inflammatory response is initiated, resulting in the expression of procoagulant molecules on the vascular endothelium and white blood cells. These surface bound procoagulants participate in the extrinsic coagulation pathway. It appears that the primary source of thrombin generation during CPB is due to extrinsic pathway activation. Thrombin not only converts fibrinogen to fibrin, it also acts as a proinflammatory agent resulting in a positive feedback loop or the inflammo-coagulatory response. Extrinsic pathway thrombin generation occurs as a membrane bound event. Membrane bound factors are resistant to heparin/ATIII inhibition. Therefore, the anticoagulant effect of heparin/ATIII is due to thrombin inhibition, not the inhibition of thrombin generation. Interpretation of the activated clotting time (ACT) must take into account the thrombin concentration [T]; this results in the coagulatory ratio, ACT is proportional to ([Hep -ATIII]/[T]). Considering this proportionality, it can be seen that the ACT cannot be used to quantitate heparin concentration. Changes in the ACT can reflect changes in [Hep - ATIII], changes in [T], or changes in both concentrations. Anti-inflammatory agents which suppress or inhibit the extrinsic pathway, such as aprotinin, result in decreased thrombin generation. As thrombin generation decreases, the ACT-heparin dose response curve is warped, resulting in a dose response curve resembling a PTT heparin dose response curve. We can no longer assume that the disproportionate rise in the ACT relative to the [HEP - ATIII] when aprotinin is used as indicative of failure of the ACT to provide a credible indication of anticoagulation. PMID- 11192305 TI - Does heparin pretreatment affect the haemostatic system during and after cardiopulmonary bypass? AB - In this clinical pilot study, the influence of heparin pretreatment on the haemostatic system during and after cardiopulmonary bypass (CPB) was investigated. Thirteen patients scheduled for elective coronary artery bypass grafting (CABG) were divided into two groups: heparin pretreated (HP, n = 6) and non-heparin pretreated (NHP, n = 7). Blood samples were taken for measurements of plasma antithrombin-III (AT-III) activity, plasma heparin levels, activated clotting time with (HACT) and without (ACT) heparinase, whole blood platelet function, platelet count, thrombin-antithrombin-III complexes and D-dimer levels. Also, the mediastinal blood loss within the initial 20 h after surgery, and the blood transfusion requirements were monitored. The mean duration of the heparin pretreatment was 55 h (range 24-161 h). There was no significant difference in plasma AT-III activity and platelet count between the groups. Before and after CPB, the platelet responsiveness was better in the NHP group (p < 0.05). The HACT was prolonged in the NHP group during and after CPB compared to baseline values (p < 0.05), whereas, in the HP group, no significant changes were found. Plasma heparin levels and ACT values suggested adequate anticoagulation during CPB. However, the extent of thrombin inhibition and fibrinolysis increased with time on CPB, but did not differ between the two groups. Twenty hours after surgery, the thrombin inhibition showed to be significantly higher in the NHP group. Furthermore, mediastinal blood loss showed a tendency to be lower in the HP group (p = 0.08). However, there was no difference in blood transfusion requirements between the groups. These data suggest that short-term heparin pretreatment affects the perioperative platelet responsiveness and attenuates the consumption of coagulation factors. PMID- 11192306 TI - Modified ultrafiltration removes serum interleukin-8 in adult cardiac surgery. AB - Cardiopulmonary bypass (CPB) causes an increase in serum cytokine levels and systemic inflamatory responses, which may trigger the onset of various types of postoperative organ failure. In the present study, modified ultrafiltration (MUF) was applied in cases of adult cardiac surgery and an attempt was made to determine whether MUF reduces serum interleukin-8 (IL-8) levels. Nine patients who underwent cardiovascular surgery with CPB and MUF between June 1996 and June 1997 were compared with nine control patients who underwent cardiovascular surgery without MUF in the same period. Modified ultrafiltration was performed, based on a method proposed elsewhere. Serum IL-8 was measured by enzyme immunoassay at the start of CPB, immediately after CPB, immediately after MUF and 3 h after MUF. The mean filtrated volume was 1550.0 +/- 173.2 ml. In the MUF group, haematocrit increased significantly from 21.2 +/- 2.0 to 24.9 +/- 3.3% (p = 0.0008), while systolic blood pressure increased from 97.5 +/- 16.7 to 116.5 +/ 23.9 mmHg (p = 0.0024) after MUF. In contrast, there were no changes in either haematocrit or blood pressure in the control group. In the MUF group, serum IL-8 was reduced from 69.5 +/- 33.5 to 58.9 +/- 32.4 pg/ml after MUF (p = 0.0029), whereas it was not reduced in the control group. The results of the present study suggest that MUF has beneficial effects on postoperative haemodynamics, and can reduce serum IL-8 levels in adult cardiac surgery. PMID- 11192307 TI - Leukocyte filtration in the early reperfusion phase on cardiopulmonary bypass reduces myocardial injury. AB - Improved myocardial protection and cardiopulmonary bypass (CPB) have limited, but not abolished, intraoperative myocardial damage due to surgical reperfusion injury after release of the aortic crossclamp. In this double-blind, randomized study, we evaluated whether short-term leukocyte filtration during reperfusion may further reduce myocardial damage. Thirty-eight patients with coronary artery disease were randomly assigned to CPB with (group I; n = 19) or without leukocyte filtration (group II; n = 19). There was no difference in bypass time or crossclamp time between the groups. No patient in group I required catecholamines, whereas three patients in group II were supported with adrenaline or dobutamine on the first and second postoperative day. In addition, troponin T plasma levels were lower in group I (p < 0.05), whereas other markers for tissue injury (CK, CK-MB, LDH, S-GOT and S100B) did not differ. In conclusion, leukocyte filtration during reperfusion may further improve CPB by reducing myocardial damage. PMID- 11192308 TI - Leucodepletion during cardiopulmonary bypass reduces blood transfusion and crystalloid requirements. AB - Cardiopulmonary bypass (CPB) is associated with the production of inflammatory responses, which can have significant influence on prognosis. We studied the effects of leucocyte-depletion filters on inflammatory parameters and early postoperative prognosis during coronary revascularization. Twenty patients undergoing elective coronary revascularization were randomly divided into two groups. Ten patients had leucocyte-depletion filters added to the CPB circuit (treatment group) and 10 were used as control cases (control group). Expression of CD11b on neutrophils, and production of myeloperoxidase and lactoferrin, were measured in arterial samples between induction and 3 h postbypass. In addition, clinical parameters were measured during inpatient recovery. CD11b neutrophil expression, and myeloperoxidase and lactoferrin production, were found to be upregulated during CPB and then to decline to preoperative levels by the third postoperative hour. Blood transfusion requirements were reduced in the treatment group, equalling 1.5 +/- 1.2 units, compared to 2.7 +/- 1.1 units for the control group (p value = 0.034) and so were the volumes of crystalloid infused during the first 24 h postoperatively, equalling 3.9 +/- 1.21 in the treatment group and 3.3 +/- 0.71 in the control group (p value = 0.021). Overall, the application of leucocyte depletion produced an early clinical advantage, underlining the need for an improved understanding and manipulation of the inflammatory response to CPB. PMID- 11192309 TI - Oxygen free radical generation in healthy blood donors and cardiac patients: the protective effect of allopurinol. AB - Cardiopulmonary bypass (CPB) activates the complement system, which leads to granulocyte activation and free radical production. Free radical activity during CPB has been associated with myocardial dysfunction. However, the relationship between cardiac enzymes and granulocytes to lipid peroxidation in cardiac surgery patients is unknown. Moreover, the effect of allopurinol on lipid peroxidation during mechanical trauma has to be explored. Thirty-four patients undergoing coronary bypass surgery and 26 healthy blood donors participated in this prospective study where granulocyte counts, cardiac enzymes and malondialdehyde (MDA) were measured and related. Allopurinol was used ex vivo, as scavenger, to explore its effect on lipid peroxidation. In the patient group, the mean preoperative MDA level (2.2 +/- 0.7, nmol/ml) significantly increased after 30 min of bypass (3.3 +/- 0.9 nmol/ml; p < 0.0001), and showed a second peak at aortic declamping (4.1 +/- 0.9 nmol/ml). There were significant correlations between MDA and granulocyte counts (r = 0.59, p < 0.0001) and cardiac enzymes (r = 0.55, p < 0.0001). In an ex vivo setting, further mechanical trauma to blood significantly increased the MDA levels, both in the control (p < 0.0001) and in the patient group (p < 0.0001) and this effect could be reduced by allopurinol (p < 0.0001). CPB and mechanical trauma generate oxygen free radicals. Allopurinol was found to reduce lipid peroxidation of red cells following mechanical trauma and this has to be further investigated regarding its ability to reduce morbidity in patients undergoing open heart surgery. PMID- 11192310 TI - Comparison of tumor necrosis factor-alpha effect on the expression of iNOS in macrophage and cardiac myocytes. AB - Proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), are elevated during cardiopulmonary bypass (CPB), heart failure, and inflammatory cardiac and systemic diseases. Elevated TNF-alpha has been linked to diminished cardiac function, decreased systemic vascular resistance, as well as renal and pulmonary dysfunction. It is understood that myocardial tissues can express TNF alpha, which results in the induction of inducible nitric oxide synthase (iNOS) leading to a significant decline in cardiac function and other direct effects. The hypothesis of this study was to determine if TNF-alpha would stimulate iNOS and its product nitric oxide (NO) similarly in immortalized macrophage and cardiac myocytes. Cultured macrophages (RAW 264.7) and cardiac myocytes (HL-1) were placed into two treatment groups and a control. The treatments included: (1) TNF-alpha and lipopolysaccharide (LPS); and (2) LPS, TNF-alpha, interleukin-1beta (IL-1beta) and interferon-gamma (IFN-gamma) incubated for 8 h. The macrophage expression of iNOS increased by 365% (p < 0.01) and its product, NO, increased proportionally. The expression of iNOS in the cardiac myocyte did not increase with TNF-alpha and LPS. However, with the addition of IFN-alpha and IL-1beta iNOS increased to 140% of control (p < 0.05). Myocyte cGMP and NO did not increase significantly with TNF-alpha treatment. This study suggests that HL-1 myocyte iNOS cannot be induced by TNF-alpha, unlike macrophage iNOS. Furthermore, the resultant cardiac dysfunction, secondary to proinflammatory cytokines effects, is regulated via diverse pathways. PMID- 11192311 TI - Neurological injury during cardiopulmonary bypass in the rat. AB - Cerebral injury is a well-known complication of cardiac surgery. Investigations of both injury mechanisms and neuroprotective strategies have partially been limited by the lack of an adequate preclinical model of small animal cardiopulmonary bypass (CPB). We sought to determine if neurological injury could be demonstrated in a recovery model of complete CPB in the rat. Rats (n = 5) underwent 45 min of normothermic CPB followed by 24 h of recovery. Compared to sham-operated rats (n = 5), the CPB group showed a worse neurological outcome score (median, 25-75th percentile) compared to controls (5, 4-7 vs 9, 8-9, p = 0.016). This rat model of CPB may allow for the study of CPB-associated neurological injury. PMID- 11192312 TI - Cryofibrination: did it really happen? AB - Cryofibrin precipitation is a phenomenon which has only recently been described, although it might have been present since the advent of membrane oxygenators for cardiopulmonary bypass procedures. The deposition of the cold-reactive protein, cryofibrin, causes progressive occlusion of the heat-exchanger part of the cardiopulmonary circuit, thus leading to a high pressure-drop phenomenon. We describe our experience with a few cases in which the cryofibrination phenomenon developed while using the 'Avecor-Affinity Medtronic' membrane oxygenator. PMID- 11192313 TI - Role of iron in Helicobacter pylori: its influence in outer membrane protein expression and in pathogenicity. AB - The acquisition of iron is a necessity for bacterial growth in Helicobacterpylori, as it is for other organisms. In addition, iron is a critical factor for the virulence of this organism. Therefore, it is not surprising that H. pylori isolates have the potential to express at least three major iron acquisition mechanisms. The association of H. pylori infection with host iron deficiency might indicate that the iron-scavenging systems play a role in the virulence of H. pylori. PMID- 11192314 TI - Iron influences the expression of Helicobacter pylori outer membrane vesicle associated virulence factors. AB - BACKGROUND: Helicobacter pylori shed outer membrane vesicles (OMV) in vitro and in vivo. These OMV, which contain active VacA, provide a potential vehicle for the delivery of H. pylori virulence factors to the gastric mucosa. OBJECTIVE: To assess the influence of environmental iron levels on H. pylori OMV VacA and protease expression in vitro. METHODS: Three well-characterized H. pylori type strains were grown for 72 h under normal (Brucella broth, 5% fetal calf serum) and iron-limiting (Brucella broth, 5% fetal calf serum, 50 micromol/l deferoxamine) conditions. Following harvesting by differential centrifugation, the ratio of whole cells to OMV was determined. OMV VacA levels in response to iron availability were determined by ELISA and immunolabelling of washed bacteria. Protease activity was detected by zymography of OMV in the presence and absence of enzyme inhibitors and activators. HEp-2 cells were used to assay for OMV-associated cytopathogenic toxins. RESULTS: Decreased iron availability, which limited bacterial growth but not OMV release, also influenced the expression of OMV-associated virulence factors. VacA levels were reduced, whereas two new proteolytic enzymes were expressed on these OMV. When an iron salt was added to counteract the effect of the deferoxamine, VacA levels were restored in the outer membrane and the proteolytic activity disappeared. CONCLUSIONS: These results suggest that OMV release by H. pylori is influenced by environmental iron levels, and that the qualitative changes that occur in outer membrane composition may contribute to the clinical patterns of H. pylori-associated disease. PMID- 11192315 TI - Scoring system has better discriminative value than Helicobacter pylori testing in patients with dyspepsia in a setting with high prevalence of infection. AB - OBJECTIVE: To prospectively assess the accuracy of a scoring system to predict organic diseases in dyspeptic patients in an area of South Europe, and to compare it with that of Helicobacter pylori testing in patients with dyspepsia in an environment with high prevalence of H. pylori infection. METHODS: Symptoms and demographic data were recorded in 501 consecutive dyspeptic patients referred to an outpatient gastroenterology clinic. A simple scoring system was constructed from the predictive factors obtained in a multi-variate logistic regression analysis. Overall predictive accuracy was assessed with the c statistic. The model was validated using bootstrap techniques. The accuracy of clinical judgement and H. pylori testing to predict endoscopic diagnosis was also assessed. RESULTS: Organic dyspepsia (peptic ulcer, oesophagitis or malignancies) was diagnosed in 45% of the patients. The test for H. pylori was positive in 68%, and 29% of infected patients had an ulcer. The organic dyspepsia predictive model had an accuracy of 0.79, which decreased to 0.77 after validation adjustment. The predictive accuracies for clinical judgement and H. pylori testing were 0.69 and 0.61, respectively. The addition of H. pylori testing to the scoring system resulted in a minor improvement of the predictive accuracy. CONCLUSION: In an environment with a high rate of H. pylori infection and a low prevalence of peptic ulcer among infected patients, a scoring system has higher predictive accuracy for the diagnosis of organic disease than H. pylori testing. Moreover, in this setting, H. pylori testing adds a minimum value to the predictive capability of the scoring system. PMID- 11192316 TI - Helicobacter pylori infection and peptic disease in coeliac disease. AB - OBJECTIVE: To evaluate Helicobacter pylori (HP) and peptic disease prevalence in coeliac disease patients and in a control group. DESIGN: In the retrospective study, data collected on 690 upper endoscopies in coeliac patients, carried out between 1990 and 1997, were analysed. In the prospective study 263 consecutive adult patients were studied for follow-up of coeliac disease or suspected malabsorption/coeliac disease. Tests included routine blood tests; serum dosage of EMA; IgG anti-HP and, in a subgroup of participants, anti-CagA antibodies; upper endoscopy with multiple gastric and duodenal biopsies; histological examination of gastric and duodenal specimens with staining providing evidence for the presence of HP. SETTING: A centre for the treatment of malabsorptive diseases, University Federico II of Naples, Italy. PARTICIPANTS: Adults with coeliac disease at the time of diagnosis and follow-up. RESULTS: In the retrospective study, peptic disease had a prevalence of 0.72% in the endoscopy series of coeliac patients examined. In the prospective study, the prevalence of HP infection was significantly lower in untreated coeliac patients when compared with treated patients and controls (20.7%, 32.4% and 55.3%, respectively; P = 0.001, chi2). The prevalence of HP was related to both gender and age. It was found more frequently in men and the frequency increased with age in all groups. The study confirmed the low prevalence of peptic disease in coeliac patients compared with controls (0.9% vs 3.8%, P = 0.001). CONCLUSION: Patients with coeliac disease show a significantly lower prevalence of HP infection and peptic disease when compared to controls. Gluten free diet-induced changes in the intestinal environment and/or the host immuno-response may explain the increased HP prevalence in treated coeliac patients. PMID- 11192317 TI - Investigation of the association between infection with Helicobacter pylori and with TT virus, a novel DNA virus, in patients with gastroduodenal ulcer or ulcer scar. AB - OBJECTIVE: Recently, a novel DNA virus (TT virus; TTV) has been isolated. Enteric transmission is suggested as a route of transmission of TTV, with high prevalence of this virus infection in the general population, and age and geographical distributions of TTV prevalence very similar to those of Helicobacterpylori infection. We analysed an association between TTV and H. pylori infection in patients with gastroduodenal ulcer or ulcer scar. METHODS: In 181 patients with a gastroduodenal ulcer or ulcer scar (102 with a gastric lesion, 60 with a duodenal lesion, and 19 with both sites involved), specimens were cultured for H. pylori and TTV infection was sought in serum by a polymerase chain reaction. RESULTS: H. pylori infection was demonstrated in 152 patients (84.0%) and TTV was detected in 168 patients (92.8%). Patients with TTV were significantly older than those without TTV (P = 0.0001), while no age difference was observed between patients with and without H. pylori infection. No difference was apparent in the prevalence of TTV infection between patients with and without H. pylori infection, and vice versa. CONCLUSIONS: We found no association between TTV infection and H. pylori infection in patients with peptic ulcer diseases, which is consistent with a lack of association between TTV infection and peptic ulcer. However, larger studies including surveys of the general population will be required to analyse the overall association between TTV and H. pylori. PMID- 11192318 TI - Helicobacter pylori infection, gastric metaplasia in the duodenum and the relationship with ulcer recurrence. AB - OBJECTIVE: To study the prevalence of Helicobacter pylori (H. pylori) infection and gastric metaplasia (GM) in the duodenum a large group of patients with duodenal ulcer was evaluated to determine whether these factors are related to the number of ulcer recurrences. METHODS: Three hundred and seven patients diagnosed by endoscopy as having active duodenal ulcers were studied. At endoscopy, all patients had gastric biopsies taken for histology, the rapid urease test and culture. Three duodenal biopsies were also taken and processed for histology (haematoxylin & eosin, Giemsa, Warthin-Starry, and PAS stain). RESULTS: GM and H. pylori in the duodenum was identified in 73% (68-78%) and 66% (60-71%) of the cases, respectively. All patients with H. pylori in the duodenum also had GM at this location, while areas with GM but without H. pylori were described. The kappa statistic for concordance between GM and H. pylori at the duodenum was 0.82. The prevalence of GM and H. pylori, depending on the number of ulcer recurrences, was: 1st episode, 34% and 27%, respectively; 2nd episode, 84% and 80%; and > or = 3rd episode, 90% and 79% (P < 0.001 when comparing 1st vs 2nd or > or = 3rd episode). In the multivariate analysis, age and number of ulcer recurrences correlated both with GM and with H. pylori in the duodenum. Chronic duodenitis was demonstrated in all duodenal biopsies, 87% being active chronic duodenitis. H. pylori in the duodenum was more frequent in patients with active duodenitis (73%) than in those with inactive duodenitis (13%) (P < 0.001). CONCLUSIONS: Patients with recurrent ulcer disease have a higher prevalence of both GM and H. pylori infection in the duodenum, suggesting that these two factors are related with the chronicity and recurrence of duodenal ulcer disease. H. pylori infection in the duodenum always appears in areas of GM, although GM is not necessarily colonized by the organism. H. pylori infection cannot be excluded based only on the results of duodenal biopsies, as false negative results at this area are frequent. PMID- 11192319 TI - Helicobacter pylori infection delays healing of ischaemia-reperfusion induced gastric ulcerations: new animal model for studying pathogenesis and therapy of H. pylori infection. AB - OBJECTIVE: Helicobacter pylori (Hp) infection is a major risk factor of peptic ulcerations but studies on its pathogenicity are limited due to the lack of an adequate animal model. In this study we developed the new model of gastric Hp infection in rat gastric mucosa, with acute gastric erosions progressing into ulcers in animals subjected initially to ischaemia-reperfusion (I/R). DESIGN: I/R lesions were produced in rats by clamping the coeliac artery for 0.5 h followed by 1 h reperfusion and gastric inoculation with type I Hp strain (CagA and VacA positive) or type II Hp strain (CagA and VacA negative), obtained from fresh clinical isolates, or with vehicle (saline). Gastric secretion during recovery from I/R lesions was determined in a separate group of rats equipped with chronic gastric fistula to inoculate the animals with Hp and then to collect gastric juice for determination of gastric acidity and pepsin outputs as well as luminal content of somatostatin. METHODS: The animals were killed at 0, 3, 12 or 24 h and 3, 5, 10 or 15 days after Hp inoculation and the area of gastric lesions was determined planimetrically and gastric blood flow (GBF) was measured by the H2 gas clearance technique. The venous blood was withdrawn for measurement of plasma interleukin (IL)-1beta and tumour necrosis factor alpha (TNFalpha) by ELISA and plasma gastrin, luminal somatostatin by RIA and the mucosal expression of transforming growth factor (TGFalpha) was analysed using RT-PCR with specific primers. Gastric Hp infection was assessed by histology, rapid urease test and Hp culture. The effect of triple therapy with omeprazole, amoxycillin and tinidazole on Hp infection and ulcer healing was also determined. RESULTS: Ischaemia alone resulted in an immediate fall in GBF and almost complete suppression of gastric secretion but without any gastric lesions. When ischaemia was followed by 1 h of reperfusion, acute gastric erosive lesions immediately occurred, reaching a maximum at 12 h after I/R and progressing after 3 days to deeper gastric ulcers that disappeared after 15 days. In Hp-inoculated rats, the number of viable Hp colonies gradually increased, reaching maximum at day 10 with infection with type I and at day 15 with infection with type II Hp. At day 15 the difference in Hp colonization was not significantly different between the stomachs infected by type I and type II Hp. Inoculation, especially with the type I Hp strain, significantly delayed healing of I/R-induced acute lesions and accelerated their progression into deeper chronic ulcers. This effect was accompanied by a significant fall in GBF and a higher increment in plasma IL-1beta and TNFalpha levels. Gastric acid secretion, which was completely inhibited up to 12 h after I/R, returned to the control value 24 h upon completion of the I/R procedure. This return was delayed in Hp-infected rats and accompanied by a significant elevation of plasma gastrin and a decrease in luminal somatostatin. The immunoreactivity of TGFalpha and expression of TGFalpha mRNA determined by RT-PCR were well defined in intact gastric mucosa but were significantly decreased, especially in mucosa infected with type I Hp strain, at day 15 after I/R. The triple therapy which cured Hp infection completely abolished the delay in ulcer healing caused by Hp. CONCLUSIONS: (1) Gastric infection with the Hp strain expressing cagA and vacA encoded cytotoxins delays healing of I/R-induced acute gastric lesions due to an impairment of gastric microcirculation, and excessive proinflammatory cytokine release and suppression of anti-ulcer TGFalpha expression. (2) The I/R induced suppression of gastric acid secretion may contribute to the hypergastrinaemia as a secondary phenomenon and may account for the spread of Hp infection observed during the progression of acute erosions into chronic ulcers. (3) I/R induced gastric ulcers may be a useful model for studying the action of Hp infection on gastric ulcerogenesis in ischaemic stomach and for testing anti-Hp therapy. PMID- 11192320 TI - Limited usefulness of a seven-day twice-a-day quadruple therapy. AB - OBJECTIVE: To test the usefulness of a twice-a-day, simplified quadruple therapy to cure Helicobacter pylori infection. DESIGN: Helicobacter pylori-positive ulcer patients were treated with omeprazole 20 mg twice a day (b.d.), amoxicillin 1 g b.d., tinidazole 500 mg b.d. and bismuth subcitrate 240 mg b.d. for 7 days in an experimental, noncomparative pilot study. SETTING: The gastroenterology unit of a county hospital. PARTICIPANTS: Forty-four consecutive patients with peptic ulcer disease and H. pylori infection. MEASUREMENTS: Cure was tested by either endoscopy or breath test after 2 months, and by urea breath test 6 months after therapy. RESULTS: One patient was lost to follow-up. Of the remaining 43, 37 were cured at the first control, giving an intention-to-treat cure rate of 84.1% (95% CI 69-93%) and a per protocol cure rate of 86% (95% CI 71-94%). Thirty-three cured patients agreed to return for a six-month breath test. All but one were cured (long-term per protocol cure rate 82.1%; 95% CI 66-92%). CONCLUSIONS: This particular quadruple therapy is well tolerated and easy to comply with. However, cure rates did not reach 90%. PMID- 11192321 TI - Amantadine for chronic hepatitis C: pilot study in 14 patients. AB - BACKGROUND: Amantadine, a widely available antiviral drug, has been previously reported to be effective in patients with chronic hepatitis C who failed to respond to interferon-alpha therapy. Nevertheless, its efficacy has not been fully studied, particularly in naive patients. OBJECTIVE AND DESIGN: We conducted a pilot study to determine the efficacy and the safety of amantadine as initial therapy in patients with chronic hepatitis C. METHODS AND PARTICIPANTS: Fourteen consecutive patients (mean age, 40 years; M/F ratio, 9/5) with chronic hepatitis C, elevated alanine aminotransferase (ALT) and without cirrhosis were treated with a 6-month course of amantadine, 100 mg orally twice daily. Main outcome measures were ALT concentrations and serum hepatitis C virus-RNA (HCV-RNA) levels at the end of therapy. RESULTS: All adverse events were mild or moderate and were not treatment limiting. At the end of treatment, all patients had detectable serum HCV-RNA and only one patient had a normal ALT level. The serum HCV-RNA median level and the ALT median level were not significantly different at the end of treatment as compared to baseline levels. CONCLUSIONS: Our results show that amantadine alone cannot be recommended as an alternative therapy in patients with chronic hepatitis C. PMID- 11192322 TI - Administering granulocyte colony-stimulating factor to acute liver failure patients corrects neutrophil defects. AB - OBJECTIVES: Neutrophil function is defective in acute liver failure (ALF) and the in vitro ability of granulocyte colony-stimulating factor (G-CSF) to reverse these defects has been reported. The effects of administering G-CSF to ALF patients are presented in this study. DESIGN: This was a prospective, phase I/II, open label, study. SETTING: The liver intensive therapy unit at King's College Hospital, London. PARTICIPANTS: Sequential patients admitted with acute liver failure due to acetaminophen overdose. INTERVENTIONS: G-CSF was given to four groups (each n = 6) of ALF patients as a daily infusion at 25, 50, 100 or 150 microg/m2. A control group of eight patients did not receive G-CSF. MAIN OUTCOME MEASURES: Neutrophil phagocytosis and killing of Staphylococcus aureus and superoxide release before G-CSF administration and at 24 and 96 h thereafter. RESULTS: Neutrophils from patients receiving 50, 100 or 150 microg/m2 G-CSF, but not from control patients or those receiving 25 microg/m2, showed significantly increased phagocytosis and killing at 96 h. Doses of 50 or 150 microg/m2 G-CSF resulted in increased superoxide production at 96 h. No patients discontinued treatment as a consequence of side effects related to G-CSF administration. CONCLUSIONS: G-CSF administration is a safe and effective means of reversing the neutrophil defects of ALF, and may have a role in the prevention and treatment of infection in these patients. A dose of 50 microg/m2/day is as effective as higher doses and was associated with fewer side effects. PMID- 11192323 TI - Polymorphisms in tumour necrosis factor alpha, interleukin-10 and transforming growth factor beta1 genes and end-stage liver disease. AB - OBJECTIVE: To determine any relationship between polymorphisms in the genes encoding tumour necrosis factor alpha (TNFalpha), interleukin-10 (IL-10) and transforming growth factor beta1 (TGFbeta1) and end-stage liver disease. METHODS: Whole-blood samples were taken from patients attending the Scottish Liver Transplant Unit with end-stage liver disease (primary biliary cirrhosis, n = 61; alcoholic liver disease, n = 25; primary sclerosing cholangitis, n = 17; viral disease, n = 8; type 1 auto-immune hepatitis, n = 8; acute liver failure, n = 20). DNA was extracted and the polymorphisms at positions TNF -308, IL-10 -1082 and TGFbeta1 +869 and +915 were determined using sequence-specific oligonucleotide probes. Samples were also analysed from normal healthy controls. RESULTS: There was a significant difference between patients with primary sclerosing cholangitis and healthy controls, with 65% of patients (11/17) possessing at least one TNF2 allele (A at position -308) compared with 38% of controls (P = 0.02). Four of the eight patients with auto-immune hepatitis were homozygous for TNF2 while the other four were heterozygous (P = 0.001). No significant difference between controls and patients was seen in polymorphisms for IL-10 or TGFbeta1. No association between genotype and Child's class was found in primary biliary cirrhosis. CONCLUSION: Patients with primary sclerosing cholangitis and auto-immune hepatitis are more likely to possess TNF2 than normal controls. This allele has been associated with an increased production of TNFalpha in vitro and may indicate a predisposition to these inflammatory conditions. PMID- 11192324 TI - Comparison of two tubeless function tests in the assessment of mild-to-moderate exocrine pancreatic insufficiency. AB - BACKGROUND: Faecal elastase 1 (FE1) and the pancreolauryl test (PLT) are widely used for the non-invasive diagnosis of exocrine pancreatic insufficiency (EPI). Whether one of these two tests is superior for the detection of mild-to-moderate EPI is the subject of controversy. The aim of this study was to compare the diagnostic performance of the PLT and FE1 for the detection of EPI in patients with chronic pancreatitis. METHODS: Forty consecutive patients (27 males, 13 females, 23-72 years) with chronic pancreatitis based on imaging procedures (computed tomography, endoscopic retrograde pancreatography and endoscopic ultrasound) were admitted to the study. A secretin-caerulein test (SCT) was performed after an overnight fast by giving secretin (1 U/kg/h) and caerulein (100 ng/kg/h) intravenously over 90 min. Duodenal contents were aspirated at 15 min intervals and analysed for pH, bicarbonate, amylase, lipase and elastase. EPI was graded on the basis of the results of the SCT as absent, mild, moderate or severe. A serum PLT was performed in accordance with a modified protocol previously described. A commercial ELISA was used for determination of FE1. The cut-off values were > or = 4.5 mg/l for PLT and > or = 200 microg/g for FE1. and 13 severe) on the basis of the results of the SCT. The sensitivity of the PLT for diagnosing EPI of all degrees of severity was 82% (27/33), compared with 50% for FE1 (16/ 33). In patients with severe EPI, the PLT was abnormal in 100% (13/13) and FE1 was abnormal in 85% (11/13) of the cases. The sensitivity decreases for both tests in the group of mild/moderate EPI (PLT 70% (14/20), FE1 35% (7/20)). In all seven patients with normal exocrine pancreatic function, both PLT and FE1 were also normal. CONCLUSIONS: The PLT is more sensitive than FE1 for the diagnosis of mild-to-moderate EPI, and is therefore more appropriate for completing the staging of chronic pancreatitis. PMID- 11192325 TI - Blindness following gastrointestinal haemorrhage. AB - Loss of vision is a rare but well known complication of distant and recurrent haemorrhage. It shares a poor prognosis, with only 10-14% of cases likely to make a complete recovery. Visual symptoms, due to ischaemic anterior optic neuropathy, vary from blurred vision to complete loss of vision in one or both eyes. The pathogenesis of such ischaemia remains unclear. Gastrointestinal bleeding seems to be the leading cause of loss of vision secondary to haemorrhage. However, complete and permanent blindness following gastrointestinal bleeding has rarely been reported. We report the case of a 51 -year-old woman who complained of complete blindness following blood loss, secondary to peptic ulcer, and discuss the pathogenesis of such a complication. PMID- 11192326 TI - Fat and gastro-oesophageal reflux disease. AB - It is common practice to prescribe avoidance of fatty foods to patients with gastro-oesophageal reflux disease; however, there is no good evidence supporting the benefit of such a prescription. Several reports looking at gastro-oesophageal reflux after meals of different fat content have been controversial probably because of differences in caloric load, volume and osmolarity, factors which may independently influence reflux. Recent observations suggest that fatty meals do not promote gastro-oesophageal reflux nor alter the competence of the oesophagogastric junction in comparison to balanced meals, provided they contain the same energy load. The possibility that fat increases heartburn by modulating perception of acid reflux seems to have little relevance. It is concluded that, in the light of present evidence, there is no sound rationale for clinicians recommending that patients with GORD follow a low-fat diet. PMID- 11192327 TI - Gallstones in obesity and weight loss. AB - The prevalence of cholesterol gallstones is increased in obese persons. The risk is especially high in those with the highest body mass index (relative risk 5-6). Weight loss further increases the risk of gallstones: the prevalence of new gallstones reaches 10-12% after 8-16 weeks of low-calorie diet and more than 30% within 12-18 months after gastric by-pass surgery. About one-third of the stones are symptomatic. The increased prevalence of stones is mostly due to supersaturation of bile with cholesterol, because of an increased synthesis by the liver and secretion into bile. Saturation is further increased during weight loss. It returns toward normal after weight stabilization at a lower level, allowing spontaneous stone dissolution in some cases. Identified risk factors for gallstones during weight loss are a relative loss of weight greater than 24% of initial body weight, a rate of weight loss greater than 1.5 kg per week, a very low calorie diet with no fat, a long overnight fast period and a high serum triglyceride level. Ursodeoxycholic acid decreases cholesterol saturation of bile and gallstone incidence during weight loss. Other preventive measures include a control of weight loss rate, a reduction of the length of overnight fast, and maintenance of a small amount of fat in the diet. PMID- 11192328 TI - Gastric acidity and preneoplastic/neoplastic changes of the stomach. PMID- 11192329 TI - Development and validation of an ultrasonographic activity index of Crohn's disease. PMID- 11192330 TI - Control of vascular tone in the syndromes of Bartter and Gitelman. AB - Bartter's and Gitelman's syndromes can be used as models to gain insight into the mechanisms responsible for maintaining/controlling vascular tone. In fact, the study of patients with these syndromes provides important insights into mechanistic details of the most relevant pathways of vascular tone. So far, several experimental findings in patients with these syndromes point to G protein abnormalities and suggest that the intracellular signaling systems that involve the G protein complex transducing components may be defective, leading to altered vascular reactivity. These results are also of particular interest because the derangements found in Bartter's and Gitelman's syndromes are the mirror images of those involved in the pathophysiology of hypertension. PMID- 11192331 TI - Thyroid-associated ophthalmopathy: clinical features, pathogenesis, and management. AB - Thyroid-associated ophthalmopathy (TAO) is a progressive eye disorder characterized by immune-mediated inflammation of the extraocular muscles and orbital connective tissue. TAO is linked, in a unique way, with thyroid autoimmunity, in particular Graves' hyperthyroidism. Our working hypothesis for the pathogenesis of TAO is that recognition of a thyrotropin receptor (TSHR)-like protein in the orbital preadipocytes by antibodies may be the initial event leading to homing of lymphocytes into the orbital tissues. In the course of thyroid inflammation, antibodies and T cells reactive against G2s expressed in thyroid membranes cross-react with the protein in the eye muscle fiber, leading to eye muscle damage and dysfunction. Those patients with anti-G2s antibodies develop ocular myopathy. Antibodies against flavoprotein, the 64-kDa protein, which are produced in the context of eye muscle fiber damage and mitochondrial rupture, are sensitive markers of immune-mediated fiber necrosis in patients with ophthalmopathy but do not directly damage the eye muscle. Antibodies against type XIII collagen, which is localized in the plasma membranes of orbital fibroblast, may be a new marker for the congestive ophthalmopathy subtype of TAO. The measurement of antibodies against key eye muscle and orbital connective tissue autoantigens may have a role in the management of active ophthalmopathy and its prediction in patients with Graves' hyperthyroidism. PMID- 11192332 TI - Hepatic, metabolic, and nutritional disorders of alcoholism: from pathogenesis to therapy. AB - Much progress has been made in the understanding of the pathogenesis of alcoholic liver disease, resulting in an improvement in treatment. Nutritional deficiencies should be corrected when present but, because of the alcohol-induced disease process, some of the nutritional requirements change. For instance, methionine, one of the essential amino acids for humans, must be activated to S adenosylmethionine (SAMe), but, in severe liver disease, the activity of the corresponding enzyme is depressed. Therefore, the resulting deficiencies and associated pathology can be attenuated by the administration of SAMe, but not by methionine. Similarly, phosphatidylethanolamine methyltransferase (PEMT) activity, which is important for hepatic phosphatidylcholine (PC) synthesis, is also depressed in alcoholic liver disease, therefore calling for the administration of the products of the reaction. Inasmuch as free radical generation by the ethanol-induced CYP2E1 plays a key role in the oxidative stress, inhibitors of this enzyme have great promise and PPC, which is presently being evaluated clinically, is particularly interesting because of its innocuity. In view of the striking negative interaction between alcoholic liver injury and hepatitis C, an antiviral agent is eagerly awaited that, unlike Interferon, is not contraindicated in the alcoholic. Antiinflamatory agents may also be useful. In addition to steroids, down-regulators of cytokines and endotoxin are being considered. Finally, anticraving agents such as naltrexone or acamprosate should be incorporated into any contemplated therapeutic cocktail. PMID- 11192333 TI - The disablement process in very late life: a study of the oldest-old in Sweden. AB - The study examines physical and functional health problems and their relationship to the activity of daily living (ADL) disability experience of a cross-section of Swedish men and women aged over 80 years (N = 203). Using a model of disablement, the relationships among disability variables were simultaneously explored. Results confirmed relatively high rates of disability in this age group, with 36% of respondents having some basic ADL difficulty. Functional impairments (vision and grip strength) and functional limitations (upper and lower body limitations and cognition) were strongly related to disability, with functional limitations being a main driving force for disability. The role of psychosocial variables (depression, subjective health, and social integration) was explored through subsequent model testing. Results showed depression, subjective health, and social integration to potentially mediate the influence of risk factors, impairments, and limitations in the model. The study suggests that modifying psychosocial experiences can greatly affect the disability experience. PMID- 11192334 TI - Balancing parent care with other roles: interrole conflict of adult daughter caregivers. AB - This study examined interrole conflict experienced by 278 women who simultaneously occupied 4 roles: parent care provider, mother to children at home, wife, and employee. Compared with women who experienced no conflict between parent care and their other roles, women reporting parent care conflict tended to have fewer socio-economic resources, to have older children, and to be caring for parents with greater impairment. Women who reported conflicts between parent care and employment were older; had more education; had marriages of longer duration; and had older, more self-sufficient children than women who reported conflict between the parent care role and the mother role. Some evidence was found for the hypothesis that interrole conflict between parent care and other roles mediates the relationship between parent care stress and psychosocial well-being. Results suggest that one way parent care stress exerts its deleterious effects on the well-being of adult daughters is through the incompatible pressures of parent care and other roles. PMID- 11192335 TI - A reevaluation of the common factor theory of shared variance among age, sensory function, and cognitive function in older adults. AB - The common cause hypothesis of the relationship among age, sensory measures, and cognitive measures in very old adults was reevaluated. Both sensory function and processing speed were evaluated as mediators of the relationship between age and cognitive function. Cognitive function was a latent variable that comprised 3 factors including memory, speed, and verbal ability. The sample was population based and comprised very old adults (n = 894; mean age = 77.7, SD = 5.6 years) from the Australian Longitudinal Study of Ageing. The results showed that there was common variance in the cognitive factor shared by age, speed, vision, and hearing but that specific effects of age on cognition remained. Furthermore, speed did not fully mediate the effect of age or sensory function on cognition. Some age differences in cognitive performance are not explained by the same processes that explain age differences in sensory function and processing speed. PMID- 11192336 TI - Social support and treatment response in older depressed primary care patients. AB - A previously tested theoretical model that specifies relationships among depression, activities of daily living (ADL) impairment, and social support components was validated with 307 patients aged 60 and older from a multisite effectiveness trial of 3 treatments (antidepressant, placebo, Problem-Solving Treatment) for dysthymia or minor depression in primary care. Participants completed interviews and self-reports at baseline and at 6 and 12 weeks. The short-term, longitudinal data were analyzed with covariance structure modeling techniques. Consistent with the previous model, impairment in ADLs was associated with subsequent increases in depression, a larger emotionally close network that made frequent visits was associated with subsequent increases in perceived support, and perceived support was associated with subsequent decreases in depression. This last effect was significant only among participants randomly assigned to receive placebo with clinical management. The similar results in 2 different studies are a substantial validation of the theoretical model. The effect of perceived support primarily in the placebo group suggests that those with greater perceived social support and subsyndromal depression may be more likely to have a positive response to nonspecific clinical treatment components. PMID- 11192337 TI - Psychological improvements associated with behavioral and drug treatment of urge incontinence in older women. AB - The purpose of this study was to explore changes in psychological distress associated with behavioral treatment and drug treatment for urge incontinence in community-dwelling older women. Participants were 197 ambulatory, nondemented women (aged 55 years or older) with persistent urge urinary incontinence. Participants were patients in a randomized clinical trial comparing biofeedback assisted behavioral treatment, drug treatment with oxybutynin chloride, and a placebo-control condition. Psychological distress was measured before and after treatment using the Hopkins Symptom Checklist (SCL-90-R). Multivariate and univariate analyses of variance showed that the two treatment groups and the control group had similar significant improvements on the nine subscales and the global severity index. Analysis of individual SCL-90-R subscale scores revealed trends suggesting that behavioral treatment tended to produce the largest improvements. The reductions of distress were not correlated consistently with reduction of incontinence. The results of this study showed that psychological distress was significantly reduced after treatment, regardless of the type of treatment. PMID- 11192338 TI - Protecting sleep quality in later life: a pilot study of bed restriction and sleep hygiene. AB - We tested two interventions for improving sleep consolidation and depth in normal elderly participants: a modification of sleep-restriction therapy and sleep hygiene education. Twenty-one elderly participants without sleep disorders were randomized to sleep hygiene plus bed restriction (i.e., restricting time in bed by 30 minutes nightly for one year) or to sleep hygiene alone. Participants in the bed-restriction group showed a median increase in sleep efficiency of 6.1% versus 1.8% in participants receiving sleep hygiene instruction, and an increase in allnight delta EEG power. Self-reported mood on awakening in the morning showed greater improvement over the first eight weeks in the sleep-hygiene condition. The use of sleep hygiene was associated with initial improvement in daytime well-being, whereas bed restriction led to sustained improvements in sleep continuity and sleep depth. PMID- 11192339 TI - Embedding health-promoting changes into the daily lives of independent-living older adults: long-term follow-up of occupational therapy intervention. AB - The Well Elderly Study was a randomized trial in independent-living older adults that found significant health, function, and quality of life benefits attributable to a 9-month program in preventive occupational therapy (OT). All participants completing the trial were followed for an additional 6 months without further intervention and then reevaluated using the same battery of instruments. Long-term benefit attributable to preventive OT was found for the quality of interaction scale of the Functional Status Questionnaire and for six of eight scales on the RAND SF-36: physical functioning, role functioning, vitality, social functioning, role emotional, and general mental health (p<.05). Approximately 90% of the therapeutic gain observed following OT treatment was retained in follow-up. The finding of a sustained effect for preventive OT is of great public health relevance given the looming health care cost crisis associated with our nation's expanding elderly population. PMID- 11192340 TI - Severity of upper and lower extremity functional limitation: scale development and validation with self-report and performance-based measures of physical function. WHAS Research Group. Women's Health and Aging Study. AB - OBJECTIVES: To better understand disablement and transitions from impairment to disability, discrete valid measures of functional limitation are needed. This study reports the development and criterion-related validity of scales that quantify severity of upper and lower extremity functional limitation. METHODS: Data are from 3,635 cognitively intact community-dwelling women aged 65 years and older and 1,002 moderately to severely disabled participants in the Women's Health and Aging Study. Scales assessing severity of upper and lower extremity functional limitation were constructed from commonly available questions on functional difficulty. Criterion-related validity was evaluated with self-report and performance-based measures. RESULTS: The upper and lower extremity scales range from 0 to 6 and 0 to 9, respectively. Scale scores were well distributed in the disabled group and discriminated limitations in the broader community. For both scales, rates of difficulty for all ADL and IADL increased (p<.001) with increasing severity score, and percent able and mean performance on respective upper and lower extremity tasks decreased (p<.01). DISCUSSION: These scales, constructed from commonly used self-report measures of function, provide discrete measures of upper and lower functional limitation. Because these scales are distinct from measures of disability and impairment, their use should facilitate increased understanding of the disablement process. PMID- 11192341 TI - Influences of family obligations and relationships on retirement: variations by gender, race, and marital status. AB - OBJECTIVE: This study examined whether economic and care obligations for family and kin salience influence retirement decisions and whether such influences differ by race, gender, and marital status. DATA: Data from the first 2 waves of the National Survey of Families and Households were used. The sample consisted of individuals who were employed at baseline and aged 55-75 at follow-up (N = 897). Cox proportional hazard regressions were used. RESULTS: Economic kin obligations impeded the likelihood of retiring. Individuals who made financial contributions to children outside the household and White women with resident children in the household were less prone to retire. Among Blacks, household composition effects were more complex and seemed to depend on the mix of care obligations, financial obligations, and financial contributions by resident kin. Kin salience also impinged on retirement decisions. Some groups who lacked family ties (e.g., nonmarried childless men) were less inclined to retire, whereas other subgroups (e.g., nonmarried men with monthly pre-retirement contacts with children) were more likely to retire. CONCLUSIONS: Our data suggest the importance of family obligations and relationships in retirement decisions and demonstrate considerable diversity in these processes. Models of retirement should pay greater attention to the interdependence of work and family spheres and to the diversity of retirement processes among various population groups. PMID- 11192342 TI - Attachment styles in older European American and African American adults. AB - OBJECTIVES: Differential attachment styles have been linked to differential emotion regulation and ability to cope with stress in samples of young adults. There are few data on attachment styles in older adults despite the fact that attachment relationships are said to play a significant role in psychological well-being throughout the life span. The goal of the study was to examine attachment patterns in older adults. METHODS: Participants were 800 community dwelling older European Americans and African Americans (M = 74 years) living in a large urban community. Attachment measures included the family and friend intimacy subscales from the Network Analysis Profile and the Relationship Scales Questionnaire. RESULTS: In contrast to findings with younger individuals, where the majority of respondents have been found to be secure (i.e., comfortable with closeness and dependency), the majority of the present sample were found to be dismissing/avoidant (i.e., uncomfortable with closeness, compulsively self reliant). European Americans scored higher than African Americans on attachment security, whereas African Americans scored higher than European Americans on dismissing attachment. However, the assessment of relatedness based on the Network Analysis Profile, where respondents named their closest kin, indicated that African Americans had higher scores than European Americans, though their networks were smaller. DISCUSSION: Age and ethnicity differences appear to reflect cohort effects related to the impact of economic hardship on families earlier this century and racial prejudice. The high rates of dismissing attachment and low rates of secure attachment in this large urban population suggest that these individuals may be at risk for social isolation and poor health as they become older and more frail. PMID- 11192343 TI - The impact of involuntary job loss on subsequent alcohol consumption by older workers: findings from the health and retirement survey. AB - OBJECTIVE: To estimate the effect of involuntary job loss on subsequent alcohol consumption by older workers in the United States. METHODS: Using longitudinal data from the 1992 and 1994 waves of the Health and Retirement Survey, the authors estimated multivariate models to assess the impact of involuntary job loss on subsequent alcohol use. Two outcomes were investigated: reported daily alcohol consumption and onset of drinking. The analysis sample included 207 workers who experienced involuntary job loss between survey dates and a comparison group of 2,866 continuously employed workers. RESULTS: After baseline alcohol consumption and a variety of socioeconomic and illness-related covariates were controlled, involuntary job loss was not associated (p>.05) with number of daily drinks consumed at follow-up. However, among those who did not consume alcohol at baseline, individuals who suffered involuntary job loss were twice as likely as continuously employed individuals to start drinking by follow-up (OR = 2.01; CI = 1.06-3.80). The majority of those who began drinking at follow-up reported drinking less than 1 drink per day. DISCUSSION: The findings provide evidence of a significant relationship between job loss and subsequent alcohol use among baseline nondrinkers. However, the magnitude of the changes in drinking was quite modest. PMID- 11192344 TI - Changing attitudes toward aging policy in the United States during the 1980s and 1990s: a cohort analysis. AB - OBJECTIVES: This research assessed how the attitudes of Americans toward government programs that serve older people changed between the mid-1980s and late 1990s and how much of the shift was dueto intracohort change and how much was due to cohort replacement. METHODS: Data come from three nationally representative cross-sectional samples, surveyed by telephone in 1986 (N = 1.209), 1990 (N = 1,500), and 1997 (N = 1,559). RESULTS: Attitudes of Americans have become less supportive of expanding entitlement programs for older people and more supportive of cutting their costs and benefits. Between 1986 and 1997, most cohorts, particularly older adults, grew more in favor of maintaining Social Security benefit levels but less in favor of expanding them. Young adults tended to be driving the societal shift in attitudes toward decreasing benefits. Intercohort change was more important than cohort replacement in this process. Analyses of change in 2 attitude domains between 1990 and 1997 revealed that the general population felt less strongly that older people are entitled to benefits and expressed greater opposition to the associated costs. However, young adults moderated their concerns about costs as they got older, although the young adults in the cohort replacing them had become more critical of the principle of entitlement. DISCUSSION: These findings enhance the understanding of the roles that historical conditions and aging play in shaping the attitudes of adult cohorts toward public programs for older citizens. Discrepant findings based on the intercohort change in younger age groups are reconciled by differentiating maturation effects from period effects on impressionable youth. PMID- 11192345 TI - Immigration and the regional demographics of the elderly population in the United States. AB - OBJECTIVES: This research examined the impacts of past international and interregional migration flows on regional elderly population growth and distribution patterns. METHODS: The authors used 1960, 1970, 1980, and 1990 Census data and multiregional demographic models to analyze changes in the sources of regional elderly population growth rates, age compositions, and spatial distributions over time. RESULTS: Past elderly interregional migration patterns have exhibited considerable stability and have contributed less than aging-in-place in shaping regional elderly population geographies. Also the effects of immigration on elderly dependency ratios have been very modest. DISCUSSION: Little evidence exists of any significant breaks with past trends in internal elderly migration patterns. Reconstruction of elderly population changes between 1950 and 1990 reveals that the driving force behind the changes was net aging-in-place and not net migration. Finally, analysis of the possible population rejuvenating effects of immigration suggests that although its impact has contributed to lower elderly-to-worker dependency ratios, its level over the past decades has been insufficient to counteract the much stronger countervailing impact of population aging. PMID- 11192346 TI - Gender differences in the depressive effect of widowhood in later life. AB - OBJECTIVES: This study documented the stronger adverse effect of widowhood on the psychological well-being of men than that of women and explained why this gender difference in the effect of widowhood exists. METHODS: Data came from Wave 1 of the National Survey of Families and Households. Married and widowed people aged 65 and older were selected (n = 1,686). The dependent variable was the Center for Epidemiologic Studies--Depression scale (CES-D). RESULTS: Widowhood was indeed more depressing for men than women. However, this was due primarily to the fact that married men were much less depressed than married women; widowed men and women were comparably depressed. Other contributors to the stronger effect of widowhood for men included men's shorter average time since widowhood, lower frequency of church attendance, stronger dislike of domestic labor, and lessened ability to assist their children. DISCUSSION: Although widowhood has a strong depressive effect for older men, its effect for women is nonsignificant, and it explains a small proportion of the variation in depressive symptomatology. This suggests that most people, particularly women, adapt relatively well in the long run. PMID- 11192347 TI - Treatment of heart failure with beta-blockers. Mechanisms and results. AB - Sympathetic activation is a significant predictor of a poor prognosis in heart failure. Excessive stimulation with norepinephrine produces apoptosis, tachycardia and arrhythmias thereby leading to progression of left ventricular dysfunction and worsening of outcome. Beta-blockers reduce morbidity and improve cardiac function. They have been shown to improve survival (MERIT-HF, CIBIS II and US-Carvedilol Trials). A careful uptitration of dosages is achievable with a low rate of side effects. The mechanism of beta-blocker effects in heart failure are cardiac protection from beta1-adrenoceptor overstimulation, antiarrhythmic effects, reduction in heart rate and positive energetic effects or a combination thereof. PMID- 11192348 TI - Clinical trial data on the cardioprotective effects of beta-blockade. AB - In most patients with heart failure the underlying cause is coronary artery disease (CAD). They have a poor prognosis and die slowly from deteriorating cardiac function or suddenly from ventricular fibrillation or atheromatous plaque rupture. Two key aims of treatment, therefore, are to slow the progression of the underlying CAD and the resulting heart failure and to reduce the risk of sudden death. The impact of drugs on CAD and sudden death can be assessed most effectively in patients who have recovered from a myocardial infarction (post-MI patients). Beta-blockers have been studied in at least 25 trials in post-MI patients and their capacity to reduce mortality and re-infarction has been well documented. About 50% of those who die in post-MI trials die suddenly and beta blockers particularly propranolol, timolol and metoprolol have been shown to reduce the risk of sudden death significantly. Further evidence that beta blockers are cardioprotective in post-MI patients can be obtained from trials of other drugs by noting the mortality rates in those patients who were also on a beta-blocker. In three trials of antiarrhythmic drugs and two trials of ACE inhibitors, those on beta-blockers had a better prognosis. There is therefore good evidence that in a patient population known to have serious CAD, beta blockers can effectively reduce the risk of major coronary events and are particularly effective in reducing the risk of sudden death. PMID- 11192349 TI - The management of heart failure--an overview. AB - National and international societies have issued guidelines on the management of heart failure: The European Society of Cardiology, WHO, ACC/AHA Task Force Report, US Department of Health and Human Services, German Society of Cardiology. The therapeutic approaches to heart failure have undergone considerable changes during the last few years. The guidelines have to be updated almost yearly due to new results from prospective randomized studies. Although an agreement could be reached with respect to general measures and drug treatment, no agreement on mechanical devices, pacemakers and surgical interventions has been reached. The basis for medical treatment of chronic heart failure depends on diuretics, digitalis, ACE inhibitors, and beta-blockers. Calcium antagonists and other positive inotropic drugs, other than digitalis, should be avoided as far as possible. Thiazides, loop diuretics and aldosterone antagonists are needed for acute and chronic treatment of heart failure, alone or in combination (diuretic resistant heart failure!). Digitalis glycosides are needed in patients with atrial fibrillation with a fast ventricular rate or atrial flutter and in patients with systolic dysfunction, large hearts and symptomatic failure class NYHA III and IV. However, digitalis does not convert atrial fibrillation to sinus rhythm. Today there is no question that ACE inhibitors improve the prognosis of all patients with heart failure in all stages, if ejection fraction is reduced. Therefore, most patients after myocardial infarction or after having experienced pump failure due to myocarditis or cardiomyopathy are treated with ACE inhibitors and diuretics. The beneficial effects of ACE inhibitors seem to be most pronounced the worse the situation is. Relative risk reductions (mortality!) between 10% and 40% have been published depending on the severity of symptomatic left ventricular dysfunction. Those patients with high absolute risk have more to gain than those with low risk for any given "risk reduction", of course. Recent studies also indicate that most high risk cardiac patients profit from ACE inhibitors even if pump function is normal (i.e., patients with coronary heart disease, diabetes mellitus, cerebral vascular disease, hypertension) (15). AT1 antagonists can substitute for ACE inhibitors, if the latter are not tolerated due to cough. Up to now, beta-blocking agents apart from diuretics seem to be the best investigated drugs in heart failure. Large controlled studies with bisoprolol, carvedilol and metoprolol in addition to diuretics, digitalis and ACE inhibitors convincingly yielded positive results in chronic left ventricular failure patients. Reduction of mortality by 35% and even of sudden cardiac deaths by 40% have been proven beyond doubt. Thus, heart failure patients today should also receive beta-blocking agents in all stages of the disease. In the era of controlled prospective studies (evidence-based medicine), physicians are well advised to use only drugs that have been proven beneficial in large controlled studies. PMID- 11192350 TI - Beta-blockers: recognising the assets in relation to coronary artery disease. AB - Beta-blockers have been shown to reduce the risk of coronary events and reduce the mortality of patients with hypertension and in those who have had a myocardial infarction. Furthermore, the evidence for long-term benefits in these two patient groups are much more convincing for beta-blockers than for other therapeutic agents used to treat these patient groups. In spite of this beta blockers are underused because doctors believe that these drugs are contraindicated in many vulnerable patient groups. The data now available from the many trials and observational studies have shown that patients such as the elderly, those with some degree of heart failure, diabetics and those with chronic lung disease not only tolerate beta blockers but derive more benefit than more healthy patient groups. PMID- 11192351 TI - Sudden death: ACE inhibitors and beta-blockers. AB - Sudden death is extremely common in patients suffering from cardiovascular diseases. At least one third of those with hypertension and probably about half of those who survive a myocardial infarction or suffer from cardiac failure who die in a clinical trial, die suddenly. Beta-blockers reduce the risk of sudden death in patients with cardiovascular disease, particularly in those who have had a myocardial infarction or heart failure. ACE inhibitors are perhaps less effective. Other cardiovascular drugs have not been shown to reduce the risk of sudden death. PMID- 11192352 TI - Cardioprotection with beta-adrenoceptor blockers. Does lipophilicity matter? AB - Beta-blockers have several beneficial cardiovascular effects in patients with hypertension, angina pectoris, myocardial infarction, and congestive heart failure. In patients with myocardial infarction and congestive heart failure some beta-blockers have been found to reduce mortality and morbidity. The beta blockers with a proven effect on prognosis include timolol, metoprolol, propranolol, bisoprolol, and carvedilol. One important question is whether all cardiovascular effects obtained by beta-blockers can be considered to be class effects. The beta-blockers with favorable effects on prognosis include two with more selective beta1-receptor blockade (metoprolol and bisoprolol) and three non selective (timolol, propranolol and carvedilol). One non-selective beta-blocker, which also has a more pronounced class III effect, sotalol, has been studied in a large postinfarction study without a significant effect on mortality. However, sotalol reduced the incidence of reinfarction similarly to the other beta blockers with proven effect on mortality after myocardial infarction. Sotalol had no influence at all on sudden cardiac death, while all the other beta-blockers referred to above have a very marked effect on sudden cardiac death, in fact more marked than on overall mortality. The beta-blockers with proven effect on mortality and on sudden death have one property in common and that is some degreee of lipophilicity. Sotalol and atenolol are hydrophilic. From animal experimental data it has been suggested that beta-bockers with some degree of lipophilicity penetrate into the brain and have an indirect effect on vagal activity, which is of importance for prevention of ventricular fibrillation and sudden cardiac death. It can be summarized that some beta-blockers have been found to reduce mortality and sudden cardiac death in patients after myocardial infarction and in congestive heart failure, while others have not. It seems that the major properties of the beta-blockers with proven effects on mortality and sudden cardiac death are beta1-receptor blockade and some degree of lipophilicity. Until we know more about the mechanisms behind prevention of death and especially sudden cardiac death by beta-blockers, only drugs with proven effects on prognosis should be used. PMID- 11192353 TI - Achieving optimal beta1-blockade with metoprolol CR/Zok. AB - The metoprolol CR/Zok is a multi-unit formulation containing metoprolol succinate controlled release (CR/Zok) in the form of individual drug delivery units (microcapsules). Each microcapsule acts as a diffusion cell and is designed to deliver metoprolol succinate at a near constant rate for about 20 hours independently of food intake, pH and other physiological variations. Taking the half-life of metoprolol into account this yields an even plasma concentration over 24 hours with a once daily dosage scheme. The formulation allows for once daily dosing, avoiding peaks and troughs in the plasma concentration of the drug. This leads to an even beta1-blockade over 24 hours in dose ranges from 12.5 mg to 200 mg once daily. Plasma fluctuations are considerably decreased compared with immediate release formulations and cardioselectivity is well maintained also on 200 mg CR/Zok. Vital important beta1-blockade is maintained for 24 hours. Metoprolol CR/Zok is well tolerated and well-being has been shown to be improved with metoprolol CR/Zok in patients with chronic heart failure as illustrated in the findings from the MERIT-HF study. PMID- 11192354 TI - Coronary artery disease: the role of lipids, hypertension and smoking. AB - Pioneering epidemiological projects such as the Seven Countries study, and the Framingham Heart study established the classical risk factor concept for coronary heart disease (CAD). These landmark studies showed that a raised serum total cholesterol, high blood pressure (systolic and diastolic) and smoking increase the risk of developing CHD in men and women in a graded fashion. Women develop CHD about 10 years later than men and women's risk is smaller. In the years and decades following these early studies many more prospective cohort studies primarily in the US and Europe have confirmed the early findings. In Germany two occupational and one population based cohort studies have contributed further information on this topic. In addition interactions between the three classical risk factors have been quantified, demonstrating for example that smoking carries a much higher risk for CHD in persons with high cholesterol values. Most cohort studies have confirmed that the relative risks for the classical risk factors are very similar. However, the respective absolute risks can differ tremendously, indicating that many more factors such as socio-economic conditions, nutrition, physical activity and others are of importance for the development of CHD. The scientific community, however, did not accept the consistent findings from the many observational studies as proof of causality. They required evidence that the risk for CHD could be reduced when the respective risk factor(s) was (were) diminished or eliminated. The late 1960s early 1970s thus saw the beginning of the era of randomized controlled trials (RCTs) following the advice of Archibald Cochrane who once wrote "we have to find that point on the distribution curve where therapy does more good than harm". We now know from meta-analyses of RCTs that a 1% reduction in serum cholesterol produces a 2-3% decline in risk for CHD and we can achieve reductions in total cholesterol of 20% or more. Regarding treatment of high blood pressure, meta-analyses of RCTs have shown that a reduction of 1 mmHg in diastolic blood pressure (DBP) produces a 2-3% decline in risk of CHD, and we can achieve reductions in DBP on average of 5-6 mmHg. With regard to smoking cessation, observational studies have shown that within 1-5 years of cessation those who stop smoking have a 50-70% lower risk than current smokers. Thus the findings from observational studies, RCTs and studies on mechanisms have clearly established the importance of the three classical risk factors for CHD. The successful treatment of these risk factors will not only lower the burden of CHD in the population but promises to be the most effective way of improving the health of the whole population. PMID- 11192355 TI - Coronary artery disease: an inflammatory or infectious process. AB - It is well accepted that coronary artery disease is linked to an inflammatory process. It is unknown which agents may cause or accelerate coronary artery disease. An inflammation of the vessel wall may be caused by a number of mechanisms such as accumulation of glycosylated proteins in diabetic patients, oxidised LDL in patients with hypercholesterolemia or infectious agents. Among the possible infectious agents Chlamydia pneumoniae is the most likely microorganism involved in atherosclerosis. The arguments in favour of Chlamydia pneumoniae result from seroepidemiologic studies and from detection of chlamydial DNA in atherosclerotic plaques by polymerase chain reaction (PCR). In addition this microorganism is the only one that could be isolated from atherosclerotic tissue. This review summarises the present understanding of the role of an inflammatory process in the development or progression of coronary artery disease. PMID- 11192356 TI - Coronary artery disease--free radical damage, antioxidant protection and the role of homocysteine. AB - Traditional risk factors for coronary artery disease (CAD) can only explain approximately two thirds of the observed clinical events. This has maintained interest in other nutritional and biochemical factors that might contribute to the underlying pathophysiology of vascular disease. Two such factors are dietary antioxidants and plasma homocysteine. Established risk factors such as hypertension, smoking and diabetes mellitus are all associated with increased oxidative stresses due to excess free radical activity in the vascular wall. This may facilitate the development of vascular disease because of (i) increased oxidation of low-density lipoprotein (LDL) particles which increases their propensity to deposition in the vascular wall, (ii) inactivation of endothelium derived nitric oxide, and (iii) direct cytotoxicity to endothelial cells. Protective antioxidant molecules include vitamin C and vitamin E of which the latter is lipid soluble and is the primary antioxidant defence in circulating LDL particles. Epidemiological studies have suggested strongly that individuals who have high circulating concentrations or dietary intake of natural antioxidant vitamins are protected against vascular disease events (18). Furthermore, many studies have demonstrated a beneficial effect of natural and synthetic antioxidants on surrogate markers of vascular disease such as endothelial function and lipoprotein oxidation. However, large prospective randomized controlled intervention trials, mostly involving vitamin E (e.g. CHAOS, HOPE (22)), have failed to demonstrate any beneficial effect upon vascular mortality in high risk individuals. Possible reasons for these disappointing results include the pro-oxidant effects of high dose antioxidant supplements, particularly in patients with established vascular disease. Homocysteine is a sulphydryl-containing amino acid derived from the demethylation of dietary methionine. Epidemiological studies over 30 years have shown that increased concentrations of homocysteine are associated with vascular disease. This link is independent of other risk factors, is consistent across many studies and is strongly dose-related. Recently, evidence has accumulated to suggest that this link is also biologically plausible because homocysteine promotes oxidant injury to the vascular endothelium, impairs endothelium-dependent vasomotor regulation and may also alter the coagulant properties of the blood. Plasma homocysteine levels can be reduced by dietary supplements of folic acid and B vitamins. Studies are currently being undertaken to examine the impact of these vitamins in high risk patients and, thereby, establish a causative role for homocysteine in promoting vascular events. PMID- 11192357 TI - Renal disease as a risk factor for cardiovascular disease. AB - Cardiovascular disease is the major cause of death in patients with end-stage renal disease (ESRD). ESRD patients are almost invariably hypertensive. They all have acquired combined hyperlipidemia and increased Lp(a), hyperhomocysteinemia, decreased physical activity, psychosocial stress, insulin resistance, procoagulant factors, left ventricular hypertrophy, and increased oxidative stress. Diabetes mellitus, a major risk factor for both cardiovascular disease and ESRD, has become the commonest cause of ESRD. If ESRD patients choose to smoke, the additive risk is profound. Moreover, ESRD patients are becoming older and are often menopausal if female. Finally, ESRD patients have a dramatic tendency for vascular and cardiac calcification, probably related to hyperphosphatemia and hyperparathyroidism. Cardiovascular disease is also a major risk in patients with decreased renal function of nearly any degree. Data from the HDFP study showed that patients with a serum creatinine concentration > 1.5 mg/dl had a profoundly higher risk of cardiovascular disease than patients with creatinine values below this value. These data were recently corroborated in the HOPE study. Microalbuminuria (MAU), with or without diabetes mellitus, indicates increased cardiovascular disease risk even without decreases in glomerular filtration rate. We found earlier that nondiabetic hypertensive patients with MAU had much higher rates of myocardial infarction, stroke, and peripheral vascular disease, than similar hypertensive patients without MAU. In conclusion, the presence of decreased renal function or MAU is a major cardiovascular risk factor. ESRD can be regarded as a catastrophic risk factor. Prophylactic measures known to be effective in reducing the risk from cardiovascular disease are grossly underused. Unfortunately, they are less effective in patients with renal disease, and new strategies are needed. PMID- 11192358 TI - Coronary artery disease--is menopause a risk factor? AB - Cardiovascular disease, especially coronary artery disease (CAD), are leading causes of morbidity and mortality in women over the age of 50, whereas this is rarely the case in younger women. This fact, the overall lower incidence of and the 10-15 year retarded occurrence of CAD in women, has led to the controversially discussed question whether menopause is a risk factor for CAD. There has been universal agreement that surgically induced early menopause with bilateral oophorectomy is a risk factor for CAD, associated with a relative risk of 2, unless estrogen is replaced. Yet pertinent naturally occurring menopause studies showed variable results. This review focuses on the criteria required for an association to be accepted as a risk factor. The occurrence of natural menopause is influenced by preexisting risk factors in different, partly opposing ways. Smoking leads to an earlier occurrence of menopause, obesity, hypertension and diabetes to a later occurrence. These complex interactions complicate statistical analysis. Natural menopause is associated with profound biochemical and metabolic changes, which are established risk factors, e.g., increase in LDL and decrease in HDL cholesterol. These biochemical and metabolic changes are the mechanisms by which menopause can act as a risk factor. CONCLUSIONS: Menopause can be accepted as a risk factor, even if not all requirements, particularly that of reversibility, are fulfilled. The occurrence of menopause indicates the transition from a low to a higher risk for CAD in women. PMID- 11192359 TI - ACE inhibitors in heart failure: an update. AB - Angiotensin-converting enzyme (ACE) inhibitors are now accepted as part of the routine management of patients with heart failure. Their use has been mandated in all the new major mortality trials to test the efficacy of beta-blockers in heart failure. Morbidity and mortality remain high in those with heart failure even with the benefits proven for both these groups of agents. In spite of the evidence for benefit of ACE inhibitors they are persistently used in lower doses in clinical practice than tested in the large-scale trials. This was so prevalent as to allow the conduct of a substantial study, the ATLAS trial, to compare high and low dose ACE inhibition. Its equivocal findings have allowed different interpretations. Clinical experience would suggest that starting with a low dose is appropriate but the dose should be titrated then without undue delay to the levels used in the trials wherever possible. The evidence for benefit with these drugs had been obtained largely in patients with impaired systolic function. However the AIRE study selected patients with clinical evidence of heart failure after myocardial infarction rather than with impaired systolic function. A substantial and long-term benefit was found from ACE inhibition. A cohort of patients had ventricular function assessed and as anticipated almost one half had preserved systolic function. Whilst the absolute benefit in lives saved was greater in the higher risk/low ejection fraction group, the relative risk reduction was not significantly different between those with preserved or impaired systolic function. The publication of the HOPE trial, although not a study of patients with heart failure, has clarified the situation considerably for those taking day to day care of patients. The HOPE study selected patients on the basis of high cardiovascular risk excluding those with known impaired systolic function. Although not an entry requirement for the study, ejection fraction was measured in a substantial majority and was above 40% indicating preservation of systolic function. The ACE inhibitor ramipril markedly reduced the combined end-point of cardiovascular death, stroke and myocardial infarction. Importantly there was a highly significant 20% risk reduction in the rate of myocardial infarction, a prospectively defined end-point, over the average four and a half year follow-up. Taken together with the retrospectively derived evidence from the heart failure trials there is now compelling evidence that the ACE inhibitors prevent myocardial infarction. The majority of patients with clinical heart failure have underlying ischaemic heart disease. Prevention of myocardial infarction and control of blood pressure are two key factors in the management of these patients irrespective of systolic ventricular function. The ACE inhibitors like the beta-blockers therefore have a pivotal role in their management. A challenge to current clinical trials is to determine whether these properties are shared to the same degree by the angiotensin antagonists or if even further gains in benefit can come from their combination. The neutral findings of the ELITE II study comparing the angiotensin antagonist, losartan, with the ACE inhibitor, captopril, have heightened interest in the on-going trials addressing these issues. PMID- 11192360 TI - The background of the MERIT-HF trial. AB - In the not so distant past, the idea of using beta-blockers as a primary therapy for congestive heart failure to improve symptoms and prognosis seemed paradoxical. The cardiac community reacted with skepticism when, in 1975, the pioneering report of Waagstein et al. appeared in the British Heart Journal. Since then numerous groups have investigated the effects of beta-adrenoceptor antagonists in patients with congestive heart failure. Unfortunately, the results of these trials have sometimes contradicted one another. Exercise tolerance and left ventricular ejection fraction improved in the trials with a duration of treatment of longer than 3 months, but no benefit was observed when beta-blockers were administered for only 1 month. Now, in the year 2000 we have proof for the concept that beta-blockade improves symptoms and prolongs life in heart failure. Three large placebo-controlled clinical trials with more than 9000 patients have shown that carvedilol, bisoprolol and metoprolol significantly reduce morbidity and mortality in heart failure. These agents, therefore, are clearly indicated in the majority of patients with mild to moderate heart failure. PMID- 11192361 TI - MERIT-HF--description of the trial. AB - The MERIT-HF study was a randomized, double-blind, placebo-controlled trial with a single-blind, two-week placebo run-in period. There were two primary objectives: total mortality; and the combined endpoint of total mortality or all cause hospitalizations (time to first event). Several other combined endpoints were also predefined, as were number of hospitalizations due to heart failure and other cardiovascular causes, withdrawal of study medicine due to all causes, and due to worsening heart failure, and change in NYHA class. The effect on Quality of Life was assessed in a substudy. The major inclusion criteria were symptomatic heart failure for at least 3 months corresponding to NYHA class II-IV; and a left ventricular ejection fraction of 0.40 or less in 40 to 80 year old men and women. The patients had to be on optimal treatment for at least 2 weeks prior to randomization, defined in principle as any combination of diuretics and an ACE inhibitor. The recommended starting dose was half a 25 mg tablet of metoprolol CR/Zok once daily in patients in NYHA functional class III-IV, and one 25 mg tablet once daily in patients in NYHA class II. It was recommended to double the dose after each 2-week period in order to reach the highest tolerated dose aiming for a target dose level of 200 mg once daily of metoprolol CR/Zok or placebo. This dosage regimen could be modified according to the judgement of the investigator. Randomization began on February 14, 1997, and the last patient was randomized April 14, 1998. 1990 patients were randomized to metoprolol CR/Zok and 2001 to placebo. The International Steering Committee stopped the study by October 31, 1998, upon recommendation from the Independent Safety Committee. The second pre-planned interim analysis (50% point) had shown that the pre-defined criterion for termination of the study was met and exceeded. The mean follow-up time was 1 year. PMID- 11192362 TI - MERIT-HF mortality and morbidity data. AB - This survival study was designed to address whether beta-1-blockade utilizing metoprolol CR/XL (controlled release/extended release) once daily added to standard therapy reduces mortality and morbidity in patients with decreased ejection fraction and symptoms of heart failure. Enrolled in a double-blind randomized study were 3991 patients with chronic heart failure in NYHA functional class II-IV and ejection fraction < or = 0.40 stabilized on optimal standard therapy. Randomization was preceded by a 2-week single blind placebo run-in period. The study medication was uptitrated during 8 weeks starting with 12.5 mg (NYHA functional class III-IV) or 25 mg once daily (NYHA functional class II). The target dose was 200 mg once daily. The primary endpoints were all-cause mortality and combined all-cause mortality and hospitalization (time to first event) and other objectives were cause-specific data on hospitalization, NYHA functional class and quality of life. Mean follow-up time was 1 year. All-cause mortality was reduced in the metoprolol CR/XL group compared with the placebo group, 145 versus 217 deaths, 7.2% per patient year of follow-up versus 11.0% with a relative risk of 0.66 (95% CI 0.53-0.81, nominal p = 0.00009, p adjusted for interim analysis = 0.0062). This effect was consistent across all predefined subgroups. Sudden deaths were fewer in the metoprolol group (79 versus 132 deaths), RR 0.59 (p = 0.0002). Also deaths from worsening heart failure were fewer in the metoprolol group (30 versus 58 deaths), RR 0.51 (p = 0.0023). The combined endpoint total mortality or all-cause hospitalizations was also reduced by metoprolol (641 versus 767 events), RR 0.81 (p = 0.00012). Total mortality or hospitalizations due to worsening heart failure was also reduced (311 versus 439 events), RR 0.69 (p < 0.00001). The number of hospitalizations due to worsening heart failure (317 versus 451, p < 0.00001) and days in hospital due to worsening heart failure (3401 versus 5303 days, p < 0.00001) were also reduced by metoprolol. There was also an improvement in NYHA functional class, assessed by the physicians as well as the McMaster Overall Treatment Evaluation questionnaire (OTE), assessed by the patients (p = 0.028 and p = 0.089, respectively). Permanent early discontinuation was 13.9% in the metoprolol group and 15.3% in the placebo group (RR = 0.90). In conclusion, in patients with symptomatic heart failure metoprolol CR/XL once daily improved survival by 34%, sudden death by 41%, and deaths from worsening of heart failure by 49%. In addition to improvement of survival there was also a reduced need of hospitalizations for worsening heart failure and an improved NYHA functional class and of quality of life assessed in a substudy. Metoprolol was well tolerated with no difference in early discontinuation rate from placebo treatment. PMID- 11192363 TI - Effects of growth hormone on cardiac dysfunction and gene expression in genetic murine dilated cardiomyopathy. AB - Beneficial cardiac effects of growth hormone (GH) have been shown in heart failure in several settings, but studies are lacking on this and other forms of treatment in the cardiomyopathic (CM) mouse heart. In mice with dilated cardiomyopathy due to disruption of the muscle LIM protein (MLP) gene [MLP null mice (MLP-/-)], natural history was first assessed by an initial echocardiogram at 8 weeks and a later follow-up study (n = 31). In most mice, left ventricular (LV) dilation increased and/or function decreased by 5 months, and 3 of 12 mice followed for 9 months died. At the end of follow-up, 22 MLP-/- mice (average age 10.2 months) had both LV dilation and reduced LV function and were selected for studies of GH effects on cardiac function and gene expression; mice were randomized to vehicle (controls) or recombinant human (rh) GH and restudied after 2 weeks. In the GH-treated group compared to the control group, LV % fractional shortening and LV wall thickness (echocardiography) were increased, the LV dP/dtmax (catheter-tip micromanometry) was enhanced, and LV relaxation (tau) improved; however, the LV weight was not significantly increased. The LV expression of many genes was altered in MLP-/- mice, and several were influenced by GH. Thus, short-term RhGH treatment improved LV function in a setting of chronic cardiac deterioration and significantly reduced elevated LV mRNA expression of some (ANP, BNP) but not other members of the embryonic gene program. The MLP null cardiomyopathic mouse can be useful for exploring altered signaling and therapeutic interventions in heart failure. PMID- 11192364 TI - Hyperpolarization is not responsible for the acetylcholine-induced negative chronotropic action in the presence of isoproterenol. AB - It has been reported that acetylcholine hyperpolarizes the maximum diastolic potential of canine Purkinje fibers through a pathway involving a G protein and induces a decrease in their automaticity. It is unclear, however, whether the negative chronotropic action of acetylcholine in the presence of beta-adrenergic stimulation is due to the hyperpolarization of the maximum diastolic potential or a decrease in the slope of phase 4 depolarization. We used standard microelectrode techniques to study the negative chronotropic mechanism of acetylcholine in the presence of isoproterenol in adult canine Purkinje fibers. Fibers were incubated for 24 hours in Tyrode's solution alone (n = 10) or plus pertussis toxin (n = 10), and then superfused with acetylcholine (10(-9) to 10( 4) M) in the presence of isoproterenol (10(-7) M). Acetylcholine in the presence of isoproterenol significantly decreased automaticity without hyperpolarization of the maximum diastolic potential, and decreased the slope of phase 4 depolarization. The effects of acetylcholine on automaticity and the slope of phase 4 depolarization were attenuated by pertussis toxin. The present findings indicate that the negative chronotropic action of acetylcholine in the presence of isoproterenol is due to the decrease in the slope of phase 4 depolarization through a pathway involving a pertussis toxin-sensitive G protein and that it is not the result of hyperpolarization of the maximum diastolic potential. PMID- 11192365 TI - Effects of BIIB513 on ischemia-induced arrhythmias and myocardial infarction in anesthetized rats. AB - Na+/H+ exchange (NHE) plays an important role in the regulation of the intracellular pH (pHi) and in cardiac cell injury induced by ischemia and reperfusion. In the present study, we investigated the effects of BIIB513, a selective NHE-1 inhibitor on myocardial ischemia induced arrhythmias and myocardial infarction, provoked by 30 minutes of left main coronary artery occlusion followed by 2 hours of reperfusion in an anesthetized rat model. Intravenous administration of BIIB513 (0.01-3.0 mg/kg) did not induce changes in blood pressure or heart rate. BIIB513 (0.01, 0.1, 0.3, 1.0, 3.0 mg/kg) given prior to the coronary artery occlusion dose-dependently reduced ventricular premature beats, ventricular tachycardia, and a complete suppression of ventricular fibrillation down to the dose of 0.1 mg/kg. BIIB513 (0.01, 0.1, 0.3, 1.0, 3.0 mg/kg) given prior to the coronary artery occlusion dose-dependently reduced the infarct size with an ED50 value of 0.16 mg/kg. BIIB513 (1.0 mg/kg) given prior to reperfusion also reduced infarct size by 47.3 +/- 13.1%. The reduction in infarct size was accompanied by a decrease in circulating levels of creatine phosphokinase (CPK). In conclusion, the present study demonstrates the cardioprotective ability of NHE-1 inhibition during myocardial ischemia and reperfusion by reducing serious ventricular arrhythmias and myocardial infarct size in anesthetized rats. PMID- 11192366 TI - Brief preconditioning ischemia alters diacylglycerol content and composition in rabbit heart. AB - In order to give further insight into the potential role of PKC in the beneficial effects of ischemic preconditioning, we have characterized the production of diacylglycerol, the endogenous activator of PKC, and its molecular species composition in ischemic control and preconditioned hearts. Preconditioning was induced by 1 cycle of 5 min of ischemia followed by 5 min of reperfusion. In control and preconditioned groups, hearts were harvested under deep anesthesia at baseline (preischemia) and at 2, 5 and 10 min into the sustained coronary artery occlusion, i.e., preceding myocyte death. Diacylglycerol content and fatty acid composition were analyzed by thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC), respectively. Myocardial diacylglycerol content was increased at 2 min into the sustained ischemia in the control group (481 +/- 34 vs 292 +/- 64 ng x mg(-1) at baseline; p < 0.05), but was comparable to the baseline value at 5 and 10 min. In the preconditioned group, diacylglycerol production remained unchanged throughout the 10-min test ischemia (317 +/- 17 at 2 min vs 312 +/- 38 ng x mg(-1) at baseline; p = NS). A detailed analysis of the molecular species composition at the time of 2 min revealed a reduced contribution of phosphatidylinositol to diacylglycerol production in preconditioned myocardium (global correlation coefficient 0.57 vs 0.66 in control myocardium) with a trend toward an enrichment of diacylglycerol composition with some species originating from phosphatidylcholine. Thus, our study revealed that brief preconditioning ischemia: (1) prevents the increase of diacylglycerol content in the early minutes of the sustained ischemia, and (2) emphasizes the contribution of phosphatidylcholine in diacylglycerol formation to the detriment of that of phosphatidylinositol. PMID- 11192367 TI - SB 203580, an inhibitor of p38 MAPK, abolishes infarct-limiting effect of ischemic preconditioning in isolated rabbit hearts. AB - There is debate concerning the involvement of p38 mitogen-activated protein kinase (MAPK) in ischemic preconditioning (PC). At the center of the controversy are data obtained after administration of SB 203580, a specific inhibitor of p38 MAPK. Whereas several studies have reported that SB 203580 abolishes the cardioprotective effect of PC, others claim that this compound is actually cardioprotective against ischemia. Many of these latter observations have been made in isolated myocardial cells. Accordingly the present study was designed to test the effect of SB 203580 in a model of preconditioning in intact rabbit hearts in which infarct size was the end-point. Isolated hearts experienced 30 min of regional ischemia followed by 120 min of reperfusion. Infarct size was measured with triphenyltetrazolium chloride. In control hearts infarction was 30.2 +/- 3.3% of the risk zone. PC with 5 min of global ischemia and 10 min of reperfusion before the 30-min period of ischemia significantly reduced infarct size to 10.2 +/- 2.4% (P < 0.05 vs. control). SB 203580 (2 microM) added to the perfusate for 20 min starting 5 min before the index ischemia totally blocked the protection from PC (27.4 +/- 3.3% infarction). SB 203580 alone had no effect on infarct size (28.6 +/- 4.6% infarction). These results reveal that SB 203580 does not affect infarct size on its own, but selectively blocks preconditioning's anti infarct effect in the intact rabbit heart. PMID- 11192368 TI - The p38 MAPK inhibitor, SB203580, abrogates ischaemic preconditioning in rat heart but timing of administration is critical. AB - There is debate concerning the involvement of p38 mitogen activated protein kinase (MAPK) in the mediation of ischaemic preconditioning. Pharmacological inhibition of p38 MAPK with SB203580 has been reported to block preconditioning in some studies but not in others. We hypothesised that this divergence could be due to differences in the timing of inhibitor administration. Isolated rat hearts were perfused in the Langendorff mode and subjected to 35 min regional ischaemia followed by 120 min reperfusion. Hearts were then double stained with Evans' blue and triphenyltetrazolium chloride to determine risk (R) and infarct zones (I), expressed as I/R% ratios. Preconditioned hearts were subjected to 2 times 5 min global ischaemia with 10 min intervening reperfusion. SB203580 10 microM was perfused either during the preconditioning protocol (PC+/-SB-early),just prior to and during the first 15 min of the lethal ischaemia (PC+/-SB-late) or prior to regional ischaemia in the absence of preconditioning. Ischaemic preconditioning significantly limited infarct size (I/R 38.9 +/- 3.0% in control vs 13.4 +/- 2.4%, P < 0.01). In the PC+/-SB-early group, preconditioning was still fully protective (I/R% 14.6 +/- 1.0). However, in the PC+/-SB-late group, SB203580 completely blocked the protection afforded by preconditioning (I/R% 33.6 +/- 4.4%, P < 0.01 vs 13.4 +/- 2.4% in preconditioned hearts, p < 0.05). SB203580 alone did not affect infarct size when given prior to and during regional ischaemia (I/R 36.2 +/- 2.7%). These histological data are corroborated by a significant increase in p38 MAPK activation in the preconditioned hearts during sustained ischaemia in comparison with the controls. In conclusion the activation of p38 MAPK during lethal ischaemia, but not during the ischaemic preconditioning protocol, is essential for the mediation of protection and may resolve some of the earlier controversy surrounding the use of SB203580 in preconditioning studies. PMID- 11192369 TI - Evidence for an essential role of cyclooxygenase-2 as a mediator of the late phase of ischemic preconditioning in mice. AB - Recent studies have demonstrated that cyclooxygenase-2 (COX-2) is an essential mediator of the cardioprotective effects of the late phase of ischemic preconditioning (PC) in rabbits. The goal of this study was to determine whether COX-2 also plays an essential role in late PC in the mouse. B6129F2/J mice underwent a 30-min coronary occlusion followed by 24 h of reperfusion. Administration of the COX-2 selective inhibitor, NS-398, 30 min prior to the 30 min occlusion (5 mg/kg i.p.) had no appreciable effect on infarct size compared with untreated controls (58.8 +/- 2.1%, vs. 58.8 +/- 4.3% of the risk region, respectively). When mice were preconditioned with six cycles of 4-min coronary occlusion/4-min reperfusion 24 h prior to the 30-min occlusion, infarct size was markedly reduced (19.3 +/- 3.4%), indicating a late PC effect. The protective effect of late PC was completely abrogated by administration of NS-398 30 min before the 30-min coronary occlusion (67.7 +/- 3.0%), but not by administration of vehicle alone (23.6 +/- 3.7%). These results indicate that COX-2 mediates the late phase of ischemic PC in the mouse and imply that the role of this enzyme in cardioprotection is not species-specific. PMID- 11192370 TI - Regulation of angiotensinogen gene expression and protein in neonatal rat cardiac fibroblasts by glucocorticoid and beta-adrenergic stimulation. AB - We previously demonstrated the presence of components for a renin-angiotensin system in fibroblasts cultured from neonatal rat ventricles, the regulation of expression of which has not been studied. Since glucocorticoids and beta adrenergic stimuli have been implicated in cardiac hypertrophy, and function as regulators of the circulating renin-angiotensin system, we examined the effects of dexamethasone and isoproterenol on angiotensinogen mRNA levels and protein secretion in cultured neonatal rat cardiac fibroblasts. Treatment of cardiac fibroblasts for 8 h with 10 micromol/l isoproterenol or 100 nmol/l dexamethasone increased angiotensinogen mRNA levels by 246 +/- 7% and 1406 +/- 207%, respectively. Over 24 h, dexamethasone and isoproterenol increased angiotensinogen secretion by 148 +/- 32% and 123 +/- 26%, respectively. Angiotensin II, which has been reported to be a positive regulator of angiotensinogen synthesis and secretion in liver, markedly attenuated the effects of dexamethasone and isoproterenol on angiotensinogen mRNA expression and secretion. In the presence of 1 micromol/l angiotensin II, the stimulation in angiotensinogen secretion observed with dexamethasone and isoproterenol was decreased by 62% and 76%, respectively. The negative feedback of angiotensin II on angiotensinogen expression was primarily mediated through the type one angiotensin II (AT1) receptor (IC50 = 0.30 +/- 0.02 nmol/l). In summary, results from this study demonstrate that angiotensinogen mRNA levels and protein secretion in cardiac fibroblasts are positively regulated by glucocorticoid and beta-adrenergic stimulation. In addition, angiotensinogen production by cardiac fibroblasts is under negative feedback control of angiotensin II. PMID- 11192371 TI - Adaptive mechanisms of the cardiovascular system in transgenic mice--lessons from eNOS and myoglobin knockout mice. AB - Transgenic mice have turned out to be important in the analysis of cardiovascular physiology and pathology. A large number of gene knockout and overexpression models have been generated, including genes involved in blood pressure regulation, cardiac function and hemostasis. In this review we concentrate on two models, the endothelial NO synthase and the myoglobin knockout mice. It will be shown that the genetic approach of gene function analysis in mice not only provides new insight into the actual role of the encoded gene product, but also uncovers possible secondary alterations which compensate for the induced change. In the case of NOS knockout mice, upregulation of other NOS isoforms, induction of signal molecules such as prostaglandins or endothelium-derived hyperpolarizing factor may conserve the vasodilatory potential of NOS deficient vessels. In the case of myoglobin knockout mice, even structural changes may contribute to compensate a loss of gene function as shown by the elevated capillary density, which may enhance the oxygen supply to mitochondria. Thus, results obtained by the analysis of gene function in transgenic animals may differ from acute pharmacological interventions in that they reveal the striking ability of an intact organism to effectively adapt to chronic changes in gene expression. PMID- 11192372 TI - Using gene-targeted mice to investigate the pathophysiology of myocardial reperfusion injury. PMID- 11192373 TI - Mouse models of focal arterial and venous thrombosis. AB - Mouse models of arterial and venous thrombosis have gained increasing interest over the last 15 years, due to direct availability of a growing number of genetically modified mice, improved technical feasibility, standardization of new models of local thrombosis, and low maintenance costs. In order to provide an overview of suitable models for the study of arterial and venous thrombosis in mice, we have systematically searched MEDLINE electronic databases for publications reporting on murine thrombo-embolic models from 1966-1999. We found that the variety of murine thromboembolic models through 1995 was rather limited, as most methods used intravenous injections of strong coagulation triggers such as thrombin, thromboplastin and collagen, causing lethal thromboembolism. Between 1996 and the end of 1999, a number of more sophisticated murine models of local acute or chronic thrombosis have been established. They seem to be more suitable for mimicking the natural scenario of thrombosis and, therefore, are preferable models for pathophysiological or drug evaluation studies. In this paper various models are described and their advantages and limitations discussed. PMID- 11192374 TI - Mechanical ventilation of mice. AB - Due to growing interest in murine functional genomics research, there is an increasing need for physiological stable in vivo murine models. Of special importance is support and control of ventilation by artificial respiration, which is difficult to execute as a consequence of the small size of the animal and the technically demanding breathing pattern. In addition, numerous genetically altered mice show depressed spontaneous ventilation or impaired respiratory responses. After an introduction in murine respiratory physiology we describe options for ventilatory support, its monitoring and the potential side effects. This review will provide an overview on current possibilities in the field of airway support in mouse research. PMID- 11192375 TI - How is a tissue built? AB - Tissues change in many ways in the period that they are part of a living organism. They are created in fairly repeatable structural patterns, and we know that the patterns are due to both the genes and the (mechanical) environment, but we do not know exactly what part or percentage of a particular pattern to consider the genes, or the environment, responsible for. We do not know much about the beginning of tissue construction (morphogenesis) and we do not know the methods of tissue construction. When the tissue structure is altered to accommodate a new loading, we do not know how the decision is made for the structural reconstruction. We do know that tissues grow or reconstruct themselves without ceasing to continue with their structural function, but we do not understand the processes that permit them to accomplish this. Tissues change their structures to altered mechanical environments, but we are not sure how. Tissues heal themselves and we understand little of the structural mechanics of the process. With the objective of describing the interesting unsolved mechanics problems associated with these biological processes, some aspects of the formation, growth, and adaptation of living tissues are reviewed. The emphasis is on ideas and models. Beyond the objective is the hope that the work will stimulate new ideas and new observations in the mechanical and chemical aspects of developmental biology. PMID- 11192376 TI - Functional tissue engineering: the role of biomechanics. AB - "Tissue engineering" uses implanted cells, scaffolds, DNA, protein, and/or protein fragments to replace or repair injured or diseased tissues and organs. Despite its early success, tissue engineers have faced challenges in repairing or replacing tissues that serve a predominantly biomechanical function. An evolving discipline called "functional tissue engineering" (FTE) seeks to address these challenges. In this paper, the authors present principles of functional tissue engineering that should be addressed when engineering repairs and replacements for load-bearing structures. First, in vivo stress/strain histories need to be measured for a variety of activities. These in vivo data provide mechanical thresholds that tissue repairs/replacements will likely encounter after surgery. Second, the mechanical properties of the native tissues must be established for subfailure and failure conditions. These "baseline data" provide parameters within the expected thresholds for different in vivo activities and beyond these levels if safety factors are to be incorporated. Third, a subset of these mechanical properties must be selected and prioritized. This subset is important, given that the mechanical properties of the designs are not expected to completely duplicate the properties of the native tissues. Fourth, standards must be set when evaluating the repairs/replacements after surgery so as to determine, "how good is good enough?" Some aspects of the repair outcome may be inferior, but other mechanical characteristics of the repairs and replacements might be suitable. New and improved methods must also be developed for assessing the function of engineered tissues. Fifth, the effects of physical factors on cellular activity must be determined in engineered tissues. Knowing these signals may shorten the iterations required to replace a tissue successfully and direct cellular activity and phenotype toward a desired end goal. Finally, to effect a better repair outcome, cell-matrix implants may benefit from being mechanically stimulated using in vitro "bioreactors" prior to implantation. Increasing evidence suggests that mechanical stress, as well as other physical factors, may significantly increase the biosynthetic activity of cells in bioartificial matrices. Incorporating each of these principles of functional tissue engineering should result in safer and more efficacious repairs and replacements for the surgeon and patient. PMID- 11192378 TI - Direction-dependent constriction flow in a poroelastic solid: the intervertebral disc valve. AB - We hypothesize that a direction-dependent flow resistance exists in the intervertebral disc due to constriction flow in the cartilage endplates. A comparison of the hydrostatic pressure in the nucleus of the healthy intervertebral disc during daily loading with the relatively low osmotic swelling pressure during rest, suggests the necessity of such direction-dependent flow resistance to ensure that all the fluid exuded from the disc during loading is recovered during rest. A physical model demonstrating the direction-dependent resistance of constriction flow in a poroelastic solid is presented. A finite element model was developed and validated against this physical model. The finite element model showed that decrease of the constriction hole area not only increases the resistance to fluid flow, but also causes the direction-dependency of flow resistance to decrease. Through this mechanism, endplate sclerosis could affect normal daily fluid exchange in the intervertebral disc, resulting in decreased mass transport and/or dehydration of the disc. PMID- 11192379 TI - Extrinsic cell infiltration and revascularization accelerate mechanical deterioration of the patellar tendon after fibroblast necrosis. AB - This study was performed to determine the contribution of extrinsic cell infiltration and revascularization into the patellar tendon in alteration of the mechanical properties of the patellar tendon after intrinsic fibroblast necrosis using 77 rabbits. In Group I, after the patellar tendon underwent the in situ freeze-thaw treatment, a wrapping treatment was performed to inhibit any extrinsic cell infiltration into the tendon. In Group II, the patellar tendon underwent the freeze-thaw treatment without any of the wrapping treatment. In Group III, the patellar tendon underwent the same wrapping treatment but without any freeze-thaw treatment. The cell culture study demonstrated that the in situ freeze-thaw treatment killed from 97 to 100 percent of the cells in the patellar tendon. Histologically, no cells were found in the midsubstance of the patellar tendon in Group I at 1, 3, and 6 weeks. In Group II, a number of cells and some vessels were found scattered in the tendon at 3 and 6 weeks. Mechanically, the elastic modulus and the tensile strength of the patellar tendon of Group II were significantly lower than those of Groups I and III at 3 and 6 weeks. These facts suggest that extrinsic cell infiltration and revascularization from the surrounding tissues accelerate the deterioration of the mechanical properties of the patellar tendon matrix after intrinsic fibroblast necrosis. PMID- 11192377 TI - A Conewise Linear Elasticity mixture model for the analysis of tension compression nonlinearity in articular cartilage. AB - A biphasic mixture model is developed that can account for the observed tension compression nonlinearity of cartilage by employing the continuum-based Conewise Linear Elasticity (CLE) model of Curnier et al. (J. Elasticity, 37, 1-38, 1995) to describe the solid phase of the mixture. In this first investigation, the orthotropic octantwise linear elasticity model was reduced to the more specialized case of cubic symmetry, to reduce the number of elastic constants from twelve to four. Confined and unconfined compression stress-relaxation, and torsional shear testing were performed on each of nine bovine humeral head articular cartilage cylindrical plugs from 6 month old calves. Using the CLE model with cubic symmetry, the aggregate modulus in compression and axial permeability were obtained from confined compression (H-A = 0.64 +/- 0.22 MPa, k2 = 3.62 +/- 0.97 x 10(-16) m4/N.s, r2 = 0.95 +/- 0.03), the tensile modulus, compressive Poisson ratio, and radial permeability were obtained from unconfined compression (E+Y = 12.75 +/- 1.56 MPa, v- = 0.03 +/- 0.01, kr = 6.06 +/- 2.10 x 10(-16) m4/N.s, r2 = 0.99 +/- 0.00), and the shear modulus was obtained from torsional shear (mu = 0.17 +/- 0.06 MPa). The model was also employed to predict the interstitial fluid pressure successfully at the center of the cartilage plug in unconfined compression (r2 = 0.98 +/- 0.01). The results of this study demonstrate that the integration of the CLE model with the biphasic mixture theory can provide a model of cartilage that can successfully curve-fit three distinct testing configurations while producing material parameters consistent with previous reports in the literature. PMID- 11192380 TI - Static and fatigue strength of a fixation device transducer for measuring anterior cruciate ligament graft tension. AB - To determine which exercises do not overload the graft-fixation complex during intensive rehabilitation from reconstructive surgery of the anterior cruciate ligament (ACL), it would be useful to measure ACL graft loads during rehabilitative activities in vivo in humans. A previous paper by Ventura et al. (1998) reported on the design of an implantable transducer integrated into a femoral fixation device and demonstrated that the transducer could be calibrated to measure graft loads to better than 10 percent full-scale error in cadaveric knees. By measuring both the static and fatigue strengths of the transducer, the purpose of the present study was to determine whether the transducer could be safely implanted in humans without risk of structural failure. Eight devices were loaded to failure statically. Additionally, seven devices were tested using the up-and-down method to estimate the median fatigue strength at a life of 225,000 cycles. The average ultimate strength was 1856 +/- 74 N and the median fatigue strength was 441 N at a life of 225,000 cycles. The maximum graft load during normal daily activities is estimated to be 500 N and the 225,000 cycle life corresponds to that of the average healthy individual during a 12-week period. Considering that patients who have had an ACL reconstruction are less ambulatory than normal immediately following surgery and that biologic incorporation of the graft should be well developed by 12 weeks thus decreasing the load transmitted to the fixation device, the FDT can be safely implanted in humans without undue risk of structural failure. PMID- 11192381 TI - Comparison of mechanical properties of various suture repair techniques in a partially lacerated tendon. AB - The technique of surgical repair for zone two flexor tendon injuries has been debated extensively throughout the years, yet adhesion formation, suture rupture, and suture locking on the pulley edge remain possible consequences of a poor repair. The partially lacerated tendon is especially challenging to treat since there can be justification for not intervening surgically. In a partial laceration canine model we measured failure load and suture gap formation for tendons repaired with the Lee, modified four-strand Savage, Kessler, modified Kessler, and Augmented Becker core suture techniques and with a simple running peripheral suture. The modified Kessler (106.3 N, SD 18.8 N) and modified Savage (108.2 N, SD 19.9 N) repair techniques had a significantly higher failure load than the Lee (85.0 N, SD 20.6 N) suture method (P < 0.05), while there were no differences among the other techniques. There were no significant differences in resistance to gap formation among the repair techniques, with the mean values ranging from 38.9 N/mm (SD 15.7 N/mm) using the simple running suture to 53.2 N/mm (SD 25.8 N/mm) with the Kessler repair. The mean load to produce a 1.5 mm repair site gap ranged from 71.1 N (SD 21.5 N) in the Lee repair to 91.3 N (SD 22.2 N) in the Augmented Becker repair although there were no significant differences among repair methods. All repair methods were much weaker than tendons left unrepaired (184.7 N, SD 41.3 N). PMID- 11192382 TI - Effects of stress shielding on the transverse mechanical properties of rabbit patellar tendons. AB - With the aim of studying mechanisms of the remodeling of tendons and ligaments, the effects of stress shielding on the rabbit patellar tendon were studied by performing tensile and stress relaxation tests in the transverse direction. The tangent modulus, tensile strength, and strain at failure of non-treated, control patellar tendons in the transverse direction were 1272 kPa, 370 kPa, and 40.5 percent, respectively, whereas those of the tendons stress-shielded for 1 week were 299 kPa, 108 kPa, and 40.4 percent, respectively. Stress shielding markedly decreased tangent modulus and tensile strength in the transverse direction, and the decreases were larger than those in the longitudinal direction, which were determined in our previous study. For example, tensile strength in the transverse and longitudinal direction decreased to 29 and 50 percent of each control value, respectively, after 1 week stress shielding. In addition, the stress relaxation in the transverse direction of stress-shielded patellar tendons was much larger than that of nontreated, control ones. In contrast to longitudinal tensile tests for the behavior of collagen, transverse tests reflect the contributions of ground substances such as proteoglycans and mechanical interactions between collagen fibers. Ground substances provide lubrication and spacing between fibers, and also confer viscoelastic properties. Therefore, the results obtained from the present study suggest that ground substance matrix, and interfiber and fiber-matrix interactions have important roles in the remodeling response of tendons to stress. PMID- 11192383 TI - Tissue-level thresholds for axonal damage in an experimental model of central nervous system white matter injury. AB - In vivo, tissue-level, mechanical thresholds for axonal injury were determined by comparing morphological injury and electrophysiological impairment to estimated tissue strain in an in vivo model of axonal injury. Axonal injury was produced by dynamically stretching the right optic nerve of an adult male guinea pig to one of seven levels of ocular displacement (Nlevel = 10; Ntotal = 70). Morphological injury was detected with neurofilament immunohistochemical staining (NF68, SM132). Simultaneously, functional injury was determined by the magnitude of the latency shift of the N35 peak of the visual evoked potentials (VEPs) recorded before and after stretch. A companion set of in situ experiments (Nlevel = 5) was used to determine the empirical relationship between the applied ocular displacement and the magnitude of optic nerve stretch. Logistic regression analysis, combined with sensitivity and specificity measures and receiver operating characteristic (ROC) curves were used to predict strain thresholds for axonal injury. From this analysis, we determined three Lagrangian strain-based thresholds for morphological damage to white matter. The liberal threshold, intended to minimize the detection of false positives, was a strain of 0.34, and the conservative threshold strain that minimized the false negative rate was 0.14. The optimal threshold strain criterion that balanced the specificity and sensitivity measures was 0.21. Similar comparisons for electrophysiological impairment produced liberal, conservative, and optimal strain thresholds of 0.28, 0.13, and 0.18, respectively. With these threshold data, it is now possible to predict more accurately the conditions that cause axonal injury in human white matter. PMID- 11192384 TI - Geometric and mechanical properties of human cervical spine ligaments. AB - This study characterized the geometry and mechanical properties of the cervical ligaments from C2-T1 levels. The lengths and cross-sectional areas of the anterior longitudinal ligament, posterior longitudinal ligament, joint capsules, ligamentum flavum, and interspinous ligament were determined from eight human cadavers using cryomicrotomy images. The geometry was defined based on spinal anatomy and its potential use in complex mathematical models. The biomechanical force-deflection, stiffness, energy, stress, and strain data were obtained from 25 cadavers using in situ axial tensile tests. Data were grouped into middle (C2 C5) and lower (C5-T1) cervical levels. Both the geometric length and area of cross section, and the biomechanical properties including the stiffness, stress, strain, energy, and Young's modulus, were presented for each of the five ligaments. In both groups, joint capsules and ligamentum flavum exhibited the highest cross-sectional area (p < 0.005), while the longitudinal ligaments had the highest length measurements. Although not reaching statistical significance, for all ligaments, cross-sectional areas were higher in the C5-T1 than in the C2 C5 group; and lengths were higher in the C2-C5 than in the C5-T1 group with the exception of the flavum (Table 1 in the main text). Force-deflection characteristics (plots) are provided for all ligaments in both groups. Failure strains were higher for the ligaments of the posterior (interspinous ligament, joint capsules, and ligamentum flavum) than the anterior complex (anterior and posterior longitudinal ligaments) in both groups. In contrast, the failure stress and Young's modulus were higher for the anterior and posterior longitudinal ligaments compared to the ligaments of the posterior complex in the two groups. However, similar tendencies in the structural responses (stiffness, energy) were not found in both groups. Researchers attempting to incorporate these data into stress-analysis models can choose the specific parameter(s) based on the complexity of the model used to study the biomechanical behavior of the human cervical spine. PMID- 11192385 TI - Biomechanical analysis of the three-dimensional foot structure during gait: a basic tool for clinical applications. AB - A novel three-dimensional numerical model of the foot, incorporating, for the first time in the literature, realistic geometric and material properties of both skeletal and soft tissue components of the foot, was developed for biomechanical analysis of its structural behavior during gait. A system of experimental methods, integrating the optical Contact Pressure Display (CPD) method for plantar pressure measurements and a Digital Radiographic Fluoroscopy (DRF) instrument for acquisition of skeletal motion during gait, was also developed in this study and subsequently used to build the foot model and validate its predictions. Using a Finite Element solver, the stress distribution within the foot structure was obtained and regions of elevated stresses for six subphases of the stance (initial-contact, heel-strike, midstance, forefoot-contact, push-off, and toe-off) were located. For each of these subphases, the model was adapted according to the corresponding fluoroscopic data, skeletal dynamics, and active muscle force loading. Validation of the stress state was achieved by comparing model predictions of contact stress distribution with respective CPD measurements. The presently developed measurement and numerical analysis tools open new approaches for clinical applications, from simulation of the development mechanisms of common foot disorders to pre- and post-interventional evaluation of their treatment. PMID- 11192386 TI - Head injury in facial impact--a finite element analysis of helmet chin bar performance. AB - The chin bar of a motorcycle helmet protects the rider from facial and head injuries. To evaluate the protective performance of chin bars against head injuries from facial impacts, an explicit finite element method was used to simulate the Snell Memorial Foundation test and a proposed drop test. The maximum acceleration and Head Injury Criterion (HIC) were employed to assess the impact absorbing capability of the chin bar. The results showed that the proposed approach should be more practical than the Snell test, and provided more information for improving the chin bar design to protect against head injuries. The shell stiffness was important in determining the protective ability of the chin bar, but a chin bar with only an outer shell and comfort foam offered inadequate protection. An energy-absorbing liner was essential to increase the protective performance of the chin bar and the liner density should be denser than that used in the cranial portion of the helmet. For the chin bar with energy absorbing liner, a shell design that is less stiff would provide better protection. PMID- 11192387 TI - Fatigue fracture of the stem-cement interface with a clamped cantilever beam test. AB - A clamped cantilever beam test was developed to determine the fatigue crack propagation rate of the CoCr alloy/PMMA cement interface at high crack tip phase angles. A combination of finite element and experimental methods was used to determine the fatigue crack growth rates of two different CoCr alloy/PMMA cement surfaces. A crack tip phase angle of 69 deg was found, indicating that loading at the crack tip was mixed-mode with a large degree of in-plane shear loading. The energy required to propagate a crack at the interface was much greater for the plasma-sprayed CoCr surface when compared to the PMMA-precoated satin finish (p < 0.001). Both interface surfaces could be modeled using a Paris fatigue crack growth law over crack propagation rates of 10(-4) to 10(-9) m/cycle. PMID- 11192388 TI - Correlation of patellar tracking pattern with trochlear and retropatellar surface topographies. AB - The study was aimed to test the hypothesis that in the knee extension range 100 to 30 deg, the patellar "out-of-plane" tracking pattern is controlled by the passive restraint provided by the topographic interaction of the patellofemoral contacting surfaces. The out-of-plane tracking pattern, i.e., the pattern of patellar displacements not in the plane of knee extension/flexion, consists of translation in the medial-lateral direction, and rotations about the anterior posterior axis (spin) and the proximal-distal axis (tilt). Using 15 fresh-frozen knees subjected to extensor moment magnitudes comparable to those in the "static lifting" activity (foot-ground reaction = 334 N), the patellar displacements were measured using a calibrated six-degree-of-freedom electromechanical goniometer. The topographies of the trochlear and retropatellar surfaces were then measured using a calibrated traveling dial-gage arrangement and the same coordinate system used for the displacement measurements. Three indices were defined to quantify particular natural features of the three-dimensional topographies that are expected to control the patellar displacements. Correlation of the indices with their corresponding displacements showed that topographic interaction was significant in the control of all three displacements. However, for patellar spin, unlike for the other two displacements, the direction of the active quadriceps tension vector was also a significant controlling factor. Patellar medial-lateral translation was found to be controlled dominantly by the trochlear topography, while retropatellar topography also had a significant role in the control of the other two displacements. PMID- 11192389 TI - Maximal wall shear stress in arterial stenoses: application to the internal carotid arteries. AB - Maximal wall shear stress (MWSS) in the convergent part of a stenosis is calculated by the interactive boundary-layer theory. A dimensional analysis of the problem shows that MWSS depends only on a few measurable parameters. A simple relationship between MWSS and these parameters is obtained, validated, and used to calculate the magnitude of MWSS in a carotid stenosis, as a function of the patency of the circle of Willis and the stenotic pattern. This demonstrates the huge effect of collateral pathways. Elevated MWSS are observed even in moderate stenoses, provided they are associated with a contralateral occlusion, a large anterior, and narrow posterior communicating arteries, suggesting a potential risk of embolus release in this configuration. PMID- 11192390 TI - Computer simulation of intraventricular flow and pressure gradients during diastole. AB - A two-dimensional axisymmetric computer model is developed for the simulation of the filling flow in the left ventricle (LV). The computed results show that vortices are formed during the acceleration phases of the filling waves. During the deceleration phases these are amplified and convected into the ventricle. The ratio of the maximal blood velocity at the mitral valve (peak E velocity) to the flow wave propagation velocity (WPV) of the filling wave is larger than 1. This hemodynamic behavior is also observed in experiments in vitro (Steen and Steen, 1994, Cardiovasc. Res., 28, pp. 1821-1827) and in measurements in vivo with color M-mode Doppler echocardiography (Stugaard et al., 1994, J. Am. Coll. Cardiol., 24, 663-670). Computed intraventricular pressure profiles are similar to observed profiles in a dog heart (Courtois et al., 1988, Circulation, 78, pp. 661-671). The long-term goal of the computer model is to study the predictive value of noninvasive parameters (e.g., velocities measured with Doppler echocardiography) on invasive parameters (e.g., pressures, stiffness of cardiac wall, time constant of relaxation). Here, we show that higher LV stiffness results in a smaller WPV for a given peak E velocity. This result may indicate an inverse relationship between WPV and LV stiffness, suggesting that WPV may be an important noninvasive index to assess LV diastolic stiffness, LV diastolic pressure and thus atrial pressure (preload). PMID- 11192391 TI - Estimated flow resistance increase in a spiral human coronary artery segment. AB - Coronary flow estimates were made for a spiral coronary artery segment (identified from a post-mortem replica casting) by using a modified Dean number based on the approximate coil radius of curvature, as suggested earlier. The estimates were found to correlate experimental pressure drop data for helical coiled tubes. Over a physiological range of mean Reynolds numbers from 100 to 400 for blood flow through main coronary arteries, estimates of the flow resistance increase relative to a straight lumen segment ranged from about 20 to 80 percent, and were of similar magnitude to those found in a flow study in a sinuous coronary vessel segment with no spiral. PMID- 11192392 TI - Stability analysis and finite element simulation of bone remodeling model. AB - Bone remodeling is widely viewed as a dynamic process--maintaining bone structure through a balance between the opposed activities of osteoblast and osteoclast cells--in which the stability problem is often pointed out. By an analytical approach, we present a bone remodeling model applied to n unit-elements in order to analyze the stationary states and the condition of their stability. In addition, this theory has been simulated in a computer model using the Finite Element Method (FEM) to show a relationship between the bone remodeling process and the stability analysis. PMID- 11192393 TI - The impact of the Internet on quality measurement. AB - Consumers are eager for information about health. However, their use of such data has been limited to date. When consumers do consider data in making health care choices, they rely more on word-of-mouth reputation than on traditional quality measures, although this information has not necessarily been readily accessible. The Internet changes the exercise of quality measurement in several ways. First, quality information--including reputation--will be more readily available. Second, consumers will increasingly use it. Third, the Internet provides a low cost, standard platform that will make it vastly easier for providers to collect quality information and pass it on to others. However, major barriers still stand in the way of public access to quality information on the Internet as well as of having that access actually improve patients' care. PMID- 11192394 TI - Patients, physicians, and the Internet. AB - The Internet will have a profound effect on the practice and business of medicine. Physicians, eager to provide high-quality care and forced by competition to offer online services, will introduce e-mail and patient-friendly Web sites to improve administrative services and manage common medical conditions. Patients will identify more health information online and will take more responsibility for their care. The doctor/patient relationship will be altered: Some aspects of electronic communication will enhance the bond, and others will threaten it. Patients will have access to vast information sources of variable validity. Many physician organizations are preparing for the electronic transformation, but most physicians are unprepared, and many are resistant. PMID- 11192395 TI - e-Health: technologic revolution meets regulatory constraint. PMID- 11192396 TI - Self-regulation: who needs it? PMID- 11192397 TI - Virtually exposed: privacy and e-health. PMID- 11192398 TI - e-health, HIPAA, and beyond. PMID- 11192399 TI - Sovereign immunity and health care: can government be trusted? AB - When government provides or arranges for health care, it is held to lower legal standards than private parties are, especially when liability is barred by "sovereign immunity". This paper examines sovereign immunity and its implications for health care quality by comparing private-sector and government accountability in several legal contexts. It then considers whether the law should be changed; the possible relationship between limited government accountability and public mistrust of a larger government role in health care; and the potential role of disparate legal standards if a lower tier of care evolves in government programs. PMID- 11192400 TI - Measuring community benefits provided by for-profit and nonprofit hospitals. AB - Nonprofit hospitals are expected to provide benefits to their community in return for being exempt from most taxes. In this paper we develop a new method of identifying activities that should qualify as community benefits and of determining a benchmark for the amount of community benefits a nonprofit hospital should be expected to provide. We then compare estimates of nonprofits' current level of community benefits with our benchmark and show that actual provision appears to fall short. Either nonprofit hospitals as a group ought to provide more community benefits, or they are performing activities that cannot be measured. In either case, better measurement and accounting of community benefits would improve public policy. PMID- 11192401 TI - The economics of for-profit and not-for-profit hospitals. AB - This paper examines the economics of for-profit and not-for-profit hospitals through the prism of capital acquisitions. The exercise suggests that of two hospitals that are equally efficient in producing health care, the for-profit hospital would have to charge higher prices than the not-for-profit hospital would, to break even on capital acquisitions. The reasons for this divergence are (1) the typically higher cost of equity capital that for-profit hospitals face; and (2) the income taxes they must pay. The paper recommends holding tax-exempt hospitals more formally accountable for the social obligation they shoulder, in return for their tax preference. PMID- 11192402 TI - Hospital conversions, margins, and the provision of uncompensated care. PMID- 11192403 TI - Are patients a scarce resource for academic clinical research? AB - Managed care has affected clinical research at academic medical centers (AMCs) in various ways. It has reduced revenues for both faculty practice plans and major teaching hospitals, thus constraining the internal funds available for the cross subsidy of research. It has increased the amount of patient care required of academic clinicians to meet target incomes, thus reducing the time for research. Has managed care also reduced the availability of patients for academic clinical research, either indirectly by diverting patients to community hospitals or directly by constraining access to such research, including clinical trials? Consistent with other studies and based on extensive interviews at nine AMCs, this research found little evidence that patients were a scarce resource for academic clinical research. PMID- 11192404 TI - Update on the nation's health care system: 1997-1999. AB - A major component of the Community Tracking Study is biennial site visits to twelve communities randomly selected to be representative of metropolitan areas. In the second round of visits, conducted in 1998 and 1999, we found an intensification of an earlier trend toward looser forms of managed care to be causing enormous turmoil, as health care organizations stumbled over and often abandoned strategies conceived for more tightly managed care. Communities' health care systems are not evolving as many anticipated but rather have focused increasingly on horizontal consolidation and regional scope. PMID- 11192405 TI - Tracking health care costs: inflation returns. PMID- 11192406 TI - The growth of multihospital firms in California. PMID- 11192407 TI - Health care reform and the new economy. AB - The objectives and assumptions of health care reform have changed repeatedly during the past century and may now be entering a new historical phase as a result of the "new economy" rooted in information technology. In a high-growth context, proponents of reform may no longer feel obliged to bundle expanded coverage with tighter cost containment. At the same time, the new digital environment may facilitate innovations intended to inform and expand consumer choice and to improve quality. The new environment elevates "transparency" to a guiding principle. Health informatics has long been peripheral to reform and must now become more central. PMID- 11192408 TI - Old before its time: HIPAA and e-health policy. PMID- 11192409 TI - A life in health policy. PMID- 11192410 TI - Traversing the digital divide. PMID- 11192411 TI - Despierta! PMID- 11192412 TI - Health information, the Internet, and the digital divide. AB - Through an analysis of recent data on adults' and children's computer use and experiences, this DataWatch shows that use of computers and the Internet is widespread and that significant percentages of the public are already using the Internet to get health information. The surveys also show that the Internet is already a useful vehicle for reaching large numbers of lower-income, less educated, and minority Americans. However, a substantial digital divide continues to characterize computer and Internet use, with lower-income blacks especially affected. Implications for the future of health communication on the Internet also are explored. PMID- 11192413 TI - Pharmaceutical cost growth under capitation: a case study. AB - Rising drug spending has generated concern among purchasers and policymakers. This paper compares drug cost growth in a capitated system with that in managed care systems that generally did not place physicians directly at risk for drug spending. We focus on cost growth because a substantial body of literature indicates that managed care interventions that reduce the level of costs may not influence the rate of cost growth. Drug cost growth under capitation initially was below that of other systems but still above targeted rates. Over time the capitation rates rose, the amount of risk transferred to physicians declined, and spending growth accelerated. PMID- 11192414 TI - Improving care at the end of life: what does it take? PMID- 11192415 TI - Mental health benefits under SCHIP. PMID- 11192416 TI - Clinician versus policymaker. PMID- 11192417 TI - Skepticism overdone: managed care and costs. PMID- 11192418 TI - Race and patient satisfaction. PMID- 11192419 TI - Understanding the value of prevention. PMID- 11192420 TI - Two old hands and the new new thing. Interview by Rob Cunningham. PMID- 11192421 TI - The Internet and managed care: a new wave of innovation. AB - Managed care firms have been under siege in the political system and the marketplace for the past few years. The rise of the Internet has brought into being powerful new electronic tools for automating administrative and financial processes in health insurance. These tools may enable new firms or employers to create custom-designed networks connecting their workers and providers, bypassing health plans altogether. Alternatively, health plans may use these tools to create a new consumer-focused business model. While some disintermediation of managed care plans may occur, the barriers to adoption of Internet tools by established plans are quite low. Network computing may provide important leverage for health plans not only to retain their franchises but also to improve their profitability and customer service. PMID- 11192422 TI - Vaporware.com: the failed promise of the health care Internet. AB - Contrary to the claims of its well-financed promoters, the Internet will not solve the administrative redundancies, economic inefficiencies, or quality problems that have plagued the U.S. health care system for decades. These phenomena are the result of economic, organizational, legal, regulatory, and cultural conflicts rooted in a health care system grown from hybrid public and private financing; cultural expectations of unlimited access to unlimited medical resources; and the use of third-party payers rewarded to constrain those expectations. The historic inadequacy of information technology to solve health care's biggest problems is a symptom of these structural realities, not their cause. With its revolution of information access for consumers, the Internet will exacerbate the cost and utilization problems of a health care system in which patients demand more, physicians are legally and economically motivated to supply more, and public and private purchasers are expected to pay the bills. PMID- 11192423 TI - Financing the health care Internet. AB - Internet-related health care firms have accelerated through the life cycle of capital finance and organizational destiny, including venture capital funding, public stock offerings, and consolidation, in the wake of heightened competition and earnings disappointments. Venture capital flooded into the e-health sector, rising from $3 million in the first quarter of 1998 to $335 million two years later. Twenty-six e-health firms went public in eighteen months, raising $1.53 billion at initial public offering (IPO) and with post-IPO share price appreciation greater than 100 percent for eighteen firms. The technology-sector crash hit the e-health sector especially hard, driving share prices down by more than 80 percent for twenty-one firms. The industry now faces an extended period of consolidation between e-health and conventional firms. PMID- 11192424 TI - Beyond the hype: a taxonomy of e-health business models. AB - This paper describes a business model of e-commerce, its application to health care, and the reasons why the health policy community should monitor its development. The business model identifies the market barriers health e-commerce firms must overcome and provides perspective on opportunities for building a health care data infrastructure that is capable of delivering both a private and a public good. PMID- 11192425 TI - Networking health: learning from others, taking the lead. AB - The Internet provides one of the most compelling examples of the way in which government research investments can, in time, lead to innovations of broad social and economic impact. This paper reviews the history of the Internet's evolution, emphasizing in particular its relationship to biomedical computing and to the nation's health care system. Here I summarize current national research programs, emphasizing the need for greater involvement by the medical research community and leadership from federal health care agencies. PMID- 11192426 TI - [Different evolution rule of SRY gene between hominoid and Old World monkey]. AB - The complete SRY gene of P. nemaeus and M. arctiodes were amplified by using PCR and sequenced. Combined with the same regions of other primate animals, sequence analysis confirmed the conservation of HMGbox. In molecular phylogenetic tree constructed, we made the Ka/Ks value pairwise comparison of HMGbox flanking sequences both intra- and inter- Hominoid and the Old World monkey. To our interest, the pairwise comparison of species in Hominoid suggested a higher Ka/Ks ratio than that in the Old World monkey or between the Old World monkey and marmoset, which showed existent of different pattern of evolution. In addition, in Hominoid Ka/Ks ratio for HMGbox sequences was obviously on the increase. The rate of nonsynonymous substitutions per nonsynonymous site is faster than that of synonymous substitutions per synonymous site in Hominoid (driven by positive directional selection). Our analysis suggested that it might be resulted from functional change of this gene and the system error or the close relationship among Hominoid species. It is also supposed that the positive selection was functioned at the beginning of the divergence of Hominoid species. PMID- 11192427 TI - [The genetic effect of estrogen receptor(ESR) on litter size traits in pig]. AB - Litter size is one of the most important economic traits in pig production, and the more piglet numbers per litter is capable to increase pork production and bring more economic profit for pig industry. ESR (estrogen receptor) gene has been determined to be one of the major genes affecting phenotype of litter size without any genetic negative correlation to growth and carcass traits. An optimized standard PCR-RFLP protocol is employed to type 262 sows from 5 different breeds in ESR loci, and then with the computation based on linear model ESR gene is confirmed to be a major locus significantly associated with litter size (P < 0.001). The genetic effect of ESR gene is quite large in these breeds, especially in these Chinese pig population. The sows of beneficial homozygote BB produce 1.40-3.37 total number born/litter and 0.63-3.58 number born alive/litter more than the sows of non-beneficial homozygote AA do. The information found in the present study is very important and could be utilized as DNA marker for improvement of reproduction trait in practice of pig breeding. PMID- 11192428 TI - Identification of QTL affecting important traits on porcine chromosome 12. AB - To screen the whole porcine chromosome 12 for QTL affecting economically important traits, ten genetic markers were genotyped in two F2 populations generated from the cross of genetically diverse breeds: European Wild pig and commercial pig breed Pietrain (W x P), and Chinese Meishan and Pietrain (M x P). Fifty-one traits were recorded. A least squares method was used for chromosome wide screening for QTL. An association analysis between genotypes at the GH locus and traits was also carried out. The least squares analysis did not reveal the presence of genome-wide significant QTL affecting the traits, while the association study showed significant (P < 0.01) associations between GH genotypes and fatness traits in M x P, but not in W x P. F2 pigs carrying the genotype C1A2/C4A2 at the GH locus displayed the thinnest backfat (21.76 mm), while the ones carrying the genotype C2A2/C2A2 had the thickest (31.41 mm). PMID- 11192429 TI - [Observation on sex-linkage inheritance of skin color in some local breeds of chicken]. AB - The sex-linkage inheritance of skin color was observed in some local breeds of chicken. The results showed that there was a pair of melanin genes PP in autosomes in Taihe Silky Fowl, an Id gene in sex chromosome in Xianju Fowl, Xiaoshan Fowl and Beijing You Fowl, and an id gene in sex chromosome in Langshan Fowl, Gushi Fowl and Taihe Silky Fowl, respectively. The offspring produced by crossing of Taihe Silky Fowl(Male) with the fowl(Female) carrying Id gene (such as Xianju Fowl, Xiaoshan Fowl and Beijing You Fowl) can autosexingly determinate by skin color, male chicken has yellow skin, female chicken has black skin. PMID- 11192430 TI - [Developmental genetic analysis of brown rice thickness of indica rice (Oryza sativa L.)]. AB - Analysis of developmental genetic effects for brown rice thickness (BRT) trait in indica rice (Oryza sativa L.) at four different filling stages was conducted and a developmental genetic model and corresponding statistical approaches for quantitative traits of triploid endosperm in cereal crops was used. The results indicated that the diploid maternal plant, triploid endosperm and cytoplasmic genetic effects were important for BRT trait at all filling stages of rice and those effects were the major effect at initial medium, filling period and mature period respectively. The additive and dominance effects were the major effect alternatively at four filling stages of rice. Significant endosperm and maternal dominance effects for BRT suggest that the utilization of heterosis for BRT is viable. The results of conditional genetic variance components shown that the expression of new quantitative genes in endosperm, cytoplasm and maternal plant for BRT was found at most filling stages of rice. The gene expression was most active at the early filling stages, especially at the second stage (8-14 days after flowering). Near to mature period (22-28 days after flowering), however, the expression of genes decreased sharply and even closed. The phenomena that the genes expressed spasmodically, i.e. the net genetic effects equaled to zero in some filling stages were detected for some genetic effects. Dominance and cytoplasmic correlation coefficients were significant at 0.05 or 0.01 probability level in some filling stages meanwhile there were the most strong relationship between mature period and other periods for BRT. PMID- 11192431 TI - [Characterization of a wheat-Agropyron intermedium translocation line by sequential GISH and FISH]. AB - The chromosome constitution on H96276-2, which is a stable line derived from a sterile wheat-Agropyron intermedium partial amphiploid Zhong 3 cross to common wheat Hui 75, was analyzed by sequential GISH and FISH. The results of GISH using genomic DNA of Agropyron intermedium as probe showed that H96276-2 possessed 20 pairs of wheat chromosomes and one pair of translocation chromosomes of wheat and Ag. intermedium. The translocated alien chromosome fragments located on the terminals of one pair of wheat chromosomes. Furthermore, reprobing of repeat sequence pSc119 was used to identify the wheat chromosomes involved in the translocation. It was determined that the alien fragments located in the terminals of the short arms of 2B chromosomes of wheat. PMID- 11192432 TI - [Segregation distortion of molecular markers in recombinant inbred populations in soybean (G. max)]. AB - The segregation distortion of 238 molecular markers in a RILs population from cultivated/semi-wild soybean cross was analysed. 29.4% of the loci were found with segregation distortion, and direction of deviation was mainly towards cultivated variety Changnong 4. RAPD markers have a higher distortion rate than other molecular markers. PMID- 11192433 TI - [Meiosis-like reduction in the culture system for somatic embryogenesis of Arabidopsis thaliana]. AB - The somatic meiosis-like reduction was observed in some cells in the embryogenic calli of Arabidopsis thaliana. One type was somatic chromosome reductional grouping, in which the chromosomes in a cell either separated into two groups, or separated into more than two groups at prophase or metaphase. The chromosomes separated directly, the morphology of the chromosomes did not show any role of the spindle fibers. Chromosome reductional grouping happened more frequently in polyploid cells. The other type was somatic meiossi which was analogous to that existed in the process of gametogenesis, and characterized by the pairing and synapsis of homologues chromosomes. In the embryogenic calli cultured on dedifferentiation medium, about 3% of the observed cells contained haploid number of chromosomes, while the tetrad cells occurred at a frequency of about 4%. The somatic meiosis-like reduction could result in the recombination of chromosomes in the cells generated by these processes. The roles of somatic meiosis-like reduction in the somatic embryogenesis and somaclonal variations were discussed. PMID- 11192434 TI - [ScII-like protein is localized in the nuclei, chromosomes and chromosome scaffolds of Allium cepa]. AB - The nuclei were isolated from the root meristematic cells of Allium cepa and the nuclear matrices were prepared. A 135 kD polypeptide, which is equivalent to Sc II in molecular weight, was revealed in the nuclei by SDS-PAGE and was then demonstrated to be an Sc II-like protein by Western blot with an anti-chicken Sc II antiserum. Neither the 135 kD polypeptide nor the positive labelling of the anti-Sc II antiserum was found in the nuclear matrices. The immuno-fluorescence tests showed that the nuclei labelled with the anti-Sc II antiserum emanated strong, specific fluorescence, while the fluorescence of the nuclear matrices was too weak to be detected. The results of immunoelectron microscopy indicated that a large number of the gold particles were concentrated in the condensed chromatin of the nuclei, but very few gold particles were distributed in cytoplasm and nucleoplasm. These results strongly suggested that an Sc II like protein is a component of the nuclei of A. cepa and is mainly located in the condensed chromatin regions, but the nuclear matrices contain no or very little amount of that protein. By means of immunofluorescence and immunoelectron microscopy, the chromosomes and chromosomal scaffolds of A. cepa labelled with the anti-chicken Sc II antiserum were observed to send off specific fluorescence and have many gold particles representing the presence of the Sc II-like protein distributed among them. The significance of the Sc II-like protein as a novel component in the nuclei, chromosomes and chromosome scaffolds of higher plants is discussed. PMID- 11192435 TI - [Identification of quantitative trait loci associated with fruit traits in watermelon [Citullus lanantus (Thanb) Mansf] and analysis of their genetic effects]. AB - In this study, we mapped and characterized quantitative trait loci (QTL) affecting watermelon fruit traits. A total of 118 F2 progenies derived from the cross 97103 (which is a cultivar with higher total soluble solids concentration, thin rind, susceptible to Fusarium wilt disease) x PI296341(which is a wild germplasm with lower total soluble solids concentration, thick rind, resistant to Fusarium wilt disease) were used to construct a 96-markers map in watermelon. By using interval mapping 4 QTLs for total soluble solids concentration, 5 QTLs for hardness of rind, 2 QTLs for thickness of rind, 3 QTLs for weight of simple fruit, and 6 QTLs for weight of one thousand grain seeds were identified. In addition, the explained variations, additive effects and dominance effects for all detected QTLs were analyzed. PMID- 11192436 TI - [Properties and nucleotide sequence of mitochondrial plasmid-like DNA pC1 of cucumber]. AB - Four kinds of plasmid-like DNA, designated pC1, pC2, pC3 and pC4 were found in the mitochondrion of cucumber Jinyan No. 4. The circle plasmid-like DNA pC1 was cloned into the EcoR I site of pUC19 using E. coli JM109 as host. The cloned pC1 DNA was isolated and used as probes in Southern analyses of total mitochondrial DNA, nuclear DNA and chloroplast DNA. Evidences were obtained that the pC1 did not show any homology with nuclear, chloroplast, main mitochondrial genomes and the other plasmid-like DNAs. Sequence analysis revealed that pC1 was 2,889 bp long. It contained many forward and reverse repeat sequences. Three main open reading frames in pC1 were longer than 800 bp. Computer-assisted searching the nucleotide sequence in GenBank database revealed pC1 had no significant homology with known sequences of mitochondrial and plasmid-like DNA, but had homology with the E. coli, Mycobaterium tuberculosis and Anacystis nidulans genomes. The predicted proteins of pC1 main ORFs show homology with the sulfate transport system in bacteria, alga and liverwort. It suggested that pC1 may encode functional proteins. PMID- 11192437 TI - [Construction of linkage map and mapping resistance gene of Scterotinia scterotiorum in Brassica napus]. AB - Scterotinia scterotiorum (Lib.) de by is a world-wide disease, which seriously decreases the yield and the quality of oil of rapeseed. Mapping resistance genes of S. scterotiorum is of vital effect to breed new elite cultivars resisting the disease. In this paper, we reported that a RAPD linkage map was constructed, including 193 RAPD markers, 19 linkage groups and covering 1,324 cM, by using Mapmaker 3.0. On the basis of map, and resistance genes, Sc1, Sc2 and Sc3, were located in 4th, 8th and 18th linkage groups. Among three QTLs, Sc2 has the characteristics of major gene with explained 29%. The three QTLs together explained about 56% of phenotypic variation. PMID- 11192438 TI - [Subcloning and sequencing of DNA fragment related to salt tolerance in Sinorhizobium fredii RT19]. AB - A 23 kb DNA fragment related to salt tolerance was obtained from the gene library of S. fredii strain RT19. In this study, BamH I was selected to digest 23 kb DNA fragment into different length of DNA fragments. The resulting fragments were ligated with plasmid pML122, then the recombinant plasmids were transformed to competent cells of E. coli S17-1 on selective medium and three transformants TR were obtained. Two-parental mating experiments were carried out with these transformants as donor and salt sensitive S. fredii strain RC3-3 as recipient, and the transconjugant BR2 was selected on FY plates containing gentamycin and 0.4 mol/L NaCl. Thus, a 4.4 kb DNA fragment related to salt tolerance was obtained. Based on its physical map, six restriction fragments were subcloned into plasmid pUC18 for DNA sequencing. Subsequently, sequencing and analysis of 4.4 kb DNA fragment showed that fixO, fixN genes and three ORFs were obtained. PMID- 11192439 TI - [Cloning of plasmid pBMB2062 in Bacillus thuringiensis strain YBT-1520 and construction of plasmid vector with genetic stability]. AB - A small plasmid pBMB2062 in Bacillus thuringiensis strain YBT-1520 was cloned and sequenced. Its 2,062 bp sequence contains two potential open reading frames (orfs). The orf1 and orf2 encode a tentative replication initial protein consisting of 289 amino acid residues and a tentative replication protein consisting of 80 amino acid residues, respectively. Two homological plasmids were found by Blast searching. There are 23 nucleotides difference occurring among three of the plasmids. The difference occurred in the orf1 causes different encoding capability. Comparing with the orf1 in pBMB2062, the orf1 in the homological plasmids are truncated, one at the N-terminal and another at the C terminal. cDNA synthesis and PCR detection showed that the mRNA corresponding to orf1 in pBMB2062 really occurs. Shuttle vectors were constructed based on pBMB2062 and showed the ability to express insecticidal crystal gene. Under nonselective condition, recombinant plasmids based on pBMB2062 were genetically stable. PMID- 11192440 TI - Photovoltaic technology comes of age. PMID- 11192441 TI - A simple, thoughtful design provides comfort and shelter for those in need. PMID- 11192442 TI - CAD pioneer reflects on the past and the future. Interview by Jerry Laiserin. PMID- 11192443 TI - Going solo. PMID- 11192444 TI - A discourse on the complications of retrobulbar and peribulbar blockade. PMID- 11192445 TI - Effect of prophylactic antibiotics and incision type on the incidence of endophthalmitis after cataract surgery. AB - BACKGROUND: There is controversy as to the efficacy of various measures in the prophylaxis of endophthalmitis after cataract surgery. In addition, it has been suggested that clear-corneal incisions may convey an increased risk of postoperative infection. We performed a retrospective review to assess the effect of prophylactic antibiotics and incision type on the incidence of endophthalmitis after cataract surgery. METHODS: A retrospective chart review and surgeon survey were used to collect data for the 13,886 consecutive cataract operations performed between Sept. 1, 1994, and Jan. 31, 1998 by nine surgeons at a hospital based surgical unit in Saskatoon. All cataract extractions were by phacoemulsification. All cases of endophthalmitis arising from the unit are managed at the hospital except in extenuating circumstances. We assessed the effect of preoperative administration of antibiotic drops, subconjunctival antibiotic injections at the conclusion of surgery and clear-corneal versus scleral tunnel incisions on the incidence of endophthalmitis by means of univariate and multivariate Poisson regression analysis. RESULTS: The incidence of postoperative endophthalmitis was significantly lower with subconjunctival antibiotic injections than without such injections (0.011% vs. 0.179%) (p = 0.009, odds ratio 16.23 [95% confidence interval 1.92 to 137.14]). The difference in the incidence of endophthalmitis with preoperative use of antibiotic drops (0.066%) and with no antibiotic drops preoperatively (0.115%) was not significant. Similarly, the difference in the incidence of endophthalmitis with clear-corneal (0.129%) and scleral tunnel (0.050%) incisions was not significant. INTERPRETATION: Our results suggest that prophylactic subconjunctival antibiotic injections at the conclusion of cataract surgery decrease the incidence of postoperative endophthalmitis. PMID- 11192446 TI - Characteristics of patients presenting with central retinal artery occlusion with and without giant cell arteritis. AB - BACKGROUND: In patients with concurrent central retinal artery occlusion (CRAO) and giant cell arteritis (GCA), prompt recognition and early treatment are crucial to prevent further visual loss in the contralateral eye. The objective of this study was to describe a series of patients with CRAO resulting from GCA and to compare them with patients with isolated CRAO. METHODS: The patient database for a retina service in Philadelphia was searched to identify patients admitted between 1983 and 1993 with a diagnosis of biopsyproven GCA and CRAO. For every patient with CRAO caused by GCA, the next patient admitted for management of acute isolated CRAO was identified; these latter patients constituted the control group. The visual acuity and baseline characteristics of the two groups were compared. RESULTS: Eleven patients with acute CRAO and GCA were admitted during the study period. In both the case and control groups seven patients (64%) were women and nine patients (82%) were white. Six subjects (54%) in the case group and seven (64%) in the control group had a history of hypertension; the values for diabetes mellitus were two (18%) and zero respectively. Four patients (36%) with CRAO and GCA were cigarette smokers, compared with eight patients (73%) with CRAO alone. None of these differences were statistically significant. Patients with CRAO related to GCA were more likely than those with isolated CRAO to have counting fingers or better vision at presentation (odds ratio 2.22 [95% confidence interval 0.37 to 13.2]), but this trend was not statistically significant. INTERPRETATION: Patients who presented with CRAO related to GCA were more than twice as likely as those with CRAO alone to have counting fingers or better visual acuity at the time of presentation. However, owing to the small sample, the power of this study to detect a true difference between the two groups was limited. PMID- 11192447 TI - Prevalence of ocular hemorrhage in patients receiving warfarin therapy. AB - BACKGROUND: Warfarin, the drug most commonly used for outpatient anticoagulation therapy, has bleeding as its main side effect. The objective of this study was to determine the prevalence of ocular hemorrhage in patients receiving warfarin and to compare it to the prevalence in the general population. METHODS: Patients receiving warfarin therapy who were attending the anticoagulation clinic at a tertiary care hospital in Montreal between October and December 1996 received a flyer inviting them to have their eyes examined to look for "ocular bleeding." Consenting patients were examined for subconjunctival hemorrhage, gross hyphema, and vitreous and retinal hemorrhages through external ocular examination and funduscopic examination with the pupils dilated using direct and indirect ophthalmoscopy. RESULTS: Of the 1225 patients seen at the clinic 126 (10%) agreed to participate. Four patients (3%) were found to have intraretinal hemorrhage at the time of examination. All hemorrhages were visually insignificant. INTERPRETATION: The risk of retinal hemorrhage in patients without preexisting ocular disease, such as retinal neovascularization or choroidal vasculopathy, who are receiving warfarin therapy is so small that it should not deter physicians from prescribing this drug when indicated. PMID- 11192448 TI - Essential iris atrophy mimicking iris neoplasm: an ultrasound biomicroscopic study. PMID- 11192449 TI - Angioma formation: a late complication of scleral buckling surgery. PMID- 11192450 TI - Choroidal neovascularization following argon laser photocoagulation for macular edema associated with branch retinal vein obstruction. PMID- 11192451 TI - The genome of the smartest pathogen decoded: is the cholera war over? PMID- 11192452 TI - Clinical quiz. Intestinal amyloidosis. PMID- 11192453 TI - Does consensus equal correctness? PMID- 11192454 TI - Gastrointestinal decontamination: maybe we're both right (commentary). PMID- 11192455 TI - Poison centers at the millennium and beyond. PMID- 11192456 TI - Urinary excretion of trace elements in humans after sodium 2,3-dimercaptopropane 1-sulfonate challenge test. AB - OBJECTIVE: To evaluate the effects of intravenous sodium 2,3-dimercaptopropane-1 sulfonate (DMPS, Dimaval) on urinary excretion of essential trace elements in subjects who received this chelating agent as a mercury challenge test. SUBJECTS: Eleven subjects sought medical attention due to concern with the toxicity of mercury released from dental amalgam fillings. DESIGN: The subjects were given DMPS 3 mg/kg intravenously. Spot urine samples were collected 1 hour before and 1 hour after the DMPS dose for laboratory analysis. In addition to mercury, the urinary excretion of copper, zinc, selenium, magnesium, manganese, molybdenum, chromium, cobalt, and aluminum were measured. RESULTS: A significant increase in urinary excretion of mercury (3- to 107-fold) was observed after the DMPS dose. The DMPS treatment led to a 2- to 119-fold increase in copper excretion; 3- to 43.8-fold in selenium excretion; 1.6- to 44-fold in zinc excretion; and 1.75- to 42.7-fold in magnesium excretion. The excretion of manganese, chromium, cobalt, aluminium, and molybdenum remained unchanged. CONCLUSIONS: In this study, an intravenous DMPS challenge test produced a significant increase in mercury excretion and also led to an increased excretion of copper, selenium, zinc, and magnesium. PMID- 11192457 TI - Transdermal kinetics of a mercurous chloride beauty cream: an in vitro human skin analysis. AB - BACKGROUND: Crema de Belleza-Manning is a popular mercurous chloride-containing beauty cream used to smooth and lighten the complexion and treat acne. Hundreds of people in the Southwestern US border states have been identified with elevated (>20 microg/L) urine mercury levels believed to be secondary to using this cream. The kinetic characteristics of percutaneous mercury absorption are incompletely defined. The objective of this study was to determine the transdermal kinetics of two formulations of mercurous chloride from a beauty cream in an in vitro human skin model. METHODS: A proprietary formulation and an aqueous formulation of the beauty cream were studied using modified Franz diffusion cells. Mercury content in the skin samples and the underlying diffusion buffer was determined using atomic absorption spectrophotometry. RESULTS: A rapid initial increase in mercury content both in the skin and the buffer was noted for both formulations. Mercury concentrations in the aqueous samples were significantly (p < 0.05) higher in both the skin and the diffusion buffer compared to parallel samples containing glycerol. CONCLUSIONS: Mercury was readily absorbed through the skin in this in vitro human skin model. The aqueous preparation had a markedly increased rate and extent of mercury absorption relative to the proprietary formulation. PMID- 11192458 TI - Effect of age and sex on liver damage due to excess dietary copper in Fischer 344 rats. AB - OBJECTIVE: The aim of this study was to investigate the morphologic and biochemical effects of excess dietary copper in young and adult rats of different sex. METHODS: Adult Fischer 344 male and female rats were given a diet containing 1500 ppm copper for 18 weeks. Young male and female rats were fed a similar copper-loaded diet from birth until 16 weeks of age. Age- and sex-matched control rats were fed a normal rodent diet (<10 ppm copper). Serum liver enzyme activity was determined in all rats. Livers were sampled for histology, histochemistry (rhodanine), immunohistochemical detection of metallothionein and copper analysis by atomic absorption spectrophotometry. Hepatic metallothionein and zinc concentrations were measured in adult rats. RESULTS: Excess dietary copper caused substantial liver injury, as evidenced by morphologic changes and increased activity of serum ALT, GGT, and SDH. All copper-loaded rats had significantly (p< 0.05) increased hepatic copper concentrations compared to controls. However, young copper-loaded rats accumulated more hepatic copper, had more severe liver changes, and had higher serum liver enzyme activities than adult rats. Histologic changes in copper-loaded rats consisted of multifocal hepatitis and widespread single-cell necrosis. Cytoplasmic copper was detected histochemically in centroacinar zone 1 (portal) and mid-zone in copper-loaded rats. Immunoreactivity for metallothionein was prominent in necrotic hepatocytes and within inflammatory foci in copper-loaded rats. However, differences in hepatic metallothionein concentrations were not detected between adult copper-loaded and control rats. CONCLUSIONS: Young Fischer 344 rats are more susceptible than adults to copper induced liver injury. PMID- 11192459 TI - Tolerance develops to the sympathomimetic but not the local anesthetic effects of cocaine. AB - OBJECTIVES: The cardiovascular effects of cocaine are complex and include sympathomimetic as well as local anesthetic effects. The aim of the present study was to delineate cocaine toxicity in a model simulating cocaine binging patterns. DESIGN: Prospective laboratory investigation. Twelve dogs were randomized to receive 6 intravenous boluses of cocaine 5.25 mg/kg (high dose, n = 5), 3.5 mg/kg (low dose, n = 4), or placebo (n = 3) at 15-minute intervals. Arterial pressure, electrocardiogram, and serum cocaine were measured at control, then at fixed time intervals after each bolus of cocaine or placebo. Statistical significance was determined by ANOVA. RESULTS: Peak serum cocaine concentrations were 3500 ng/mL and 2167 ng/mL in the high- and low-dose groups. There were progressive decreases in mean arterial pressure in the high-dose cocaine group by as much as 32% (p = .003) after each cocaine bolus. However, in the low-dose group, increases in mean arterial pressure were observed after the initial cocaine boluses by as much as 31% (p = .013). Significant QRS prolongation was observed in both the high- and low-dose cocaine groups by as much as 65% (p < .001) and 10% (p < .03), respectively. However, the prolongation observed in the high-dose group was more pronounced and cumulative, while in the low-dose group the prolongation was transient. CONCLUSIONS: At low doses, cocaine's sympathomimetic properties predominate but tolerance develops. At high doses, cocaine's local anesthetic properties predominate, become more pronounced with repeated administration, and may have implications for cocaine-related dysrhythmias, cardiovascular collapse, and sudden death. PMID- 11192460 TI - Concentrations and frequencies of polychlorinated biphenyl congeners in a Native American population that consumes Great Lakes fish. AB - OBJECTIVE: Polychlorinated biphenyl congener profiles were examined in serum samples from 61 Native American (Ojibwa) volunteers who regularly consumed fish harvested from the Great Lakes region. A total of 93 peaks are reported which represent 126 individual chlorobiphenyls. RESULTS: When ranked by frequency, 13 peaks comprising single or co-eluting chlorobiphenyls occurred in all 61 samples (a frequency of 100%). These included chlorobiphenyls 138 + 158 + 163, 105 + 132 + 153, 180, 118, 196 + 203, 74, 182 + 187, 199, 183, 114 + 134, 195 + 208, 206, and 194. These 13 peaks also occurred at concentrations higher than those of all other measured chlorobiphenyls, except for the addition of the peak containing chlorobiphenyls 170 and 190, which was below detection in 15% of the samples and ranked fifth in average concentration. The highly chlorinated chlorobiphenyls resembled human serum profiles previously reported in the literature. METHODS: Individual chlorobiphenyls were identified using a gas chromatograph equipped with a 60-meter DB-5 capillary column and electron capture detection. CONCLUSION: When compared to other human residue analyses for fish-eating populations, the Ojibwa samples contained higher proportions of lightly chlorinated and labile chlorobiphenyls such as 8, 16 + 32, 17, 18, 25, 41 + 64 + 71, 33, 52, 110, and 129. These proportions were similar to those found in carp, whitefish, or whitefish livers harvested from the Great Lakes region. These data indicate that regular meals of lower trophic level fish, such as whitefish from the Great Lakes, may distort steady-state human chlorobiphenyl profiles with respect to certain lightly chlorinated or labile chlorobiphenyls. PMID- 11192461 TI - Clinical effects and plasma concentration determination after 2,4 dichlorophenoxyacetic acid 200 mg/kg administration in the dog. AB - OBJECTIVE: To investigate the clinical effects and to determine the 2,4 dichlorophenoxyacetic acid plasma concentrations after a dose of twice the reported LD50 (100 mg/kg) was administered orally to dogs. Investigation included electromyographic evaluations and biochemical parameter determinations, as well as observable clinical signs. METHODS: Six beagle dogs were administered 2,4 dichlorophenoxyacetic acid 200 mg/kg orally. Dogs were monitored for the development of clinical signs and were anesthetized at 24 hours for needle electromyography. Blood was collected pre- and 24-hours postadministration. Plasma was analyzed for total and unbound 2,4-dichlorophenoxyacetic acid by high performance liquid chromatography with fluorescence detection. Serum was submitted for clinical chemistry parameter analysis. Statistical analyses of the chemistry parameters were performed using paired t-tests. RESULTS: All 6 dogs survived after oral administration of twice the reported LD50. Clinical signs observed were vomiting in 33% and diarrhea in 100% of the dogs. No gait abnormalities were seen in awake dogs. Electromyographic findings revealed predominantly insertional myotonia with 1 dog having spontaneous fibrillations. Decreases from baseline measurements were seen in serum calcium, potassium, and total bilirubin. The mean total and unbound plasma 2,4-dichlorophenoxyacetic acid concentrations were 511 mg/L and 129 mg/L, respectively. CONCLUSIONS: This study demonstrates that the beagle dog is less sensitive to the acute effects of 2,4 dichlorophenoxyacetic acid than previously reported. The main clinical effects seen after oral administration of twice the reported LD50 were vomiting and diarrhea. Total and unbound plasma 2,4-dichlorophenoxyacetic acid concentrations may be a useful indicator of toxicity. PMID- 11192462 TI - Multicenter case series of valproic acid ingestion: serum concentrations and toxicity. AB - BACKGROUND: Valproic acid exposures reported to poison centers have increased more than 4-fold over the last 5 years. There are no large case series published on valproic acid ingestion. METHODS: A prospective multicenter case series of all patients reporting an ingestion of valproic acid. Data collected included: age, gender, dose ingested, concomitant medications, symptoms and vital signs, laboratory values, length of hospital stay, and medical outcome. Entrance into the study required a serum valproic acid concentration above the therapeutic threshold of 100 microg/mL. Statistical analysis was by Fisher's exact test. RESULTS: A total of 335 patients were reported to participating centers of which 186 (55%) had serum valproic acid concentrations greater than 100 microg/mL. Of the 186 cases, 53 were multiple drug exposures leaving 133 cases of sole valproic acid ingestion for evaluation. Age ranged from 2 to 66 years with a mean of 30.1 years +/- 12. Peak serum valproic acid concentrations ranged from 110 microg/mL to 1840 microg/mL with a mean of 378.3 microg/mL +/- 310.2 microg/mL. Time from postingestion to the peak measured valproic acid concentration ranged from 1 to 18 hours, with a mean of 7.4 hours +/- 3.9. Symptoms included lethargy (n = 94), coma (n = 19), tachycardia (n = 24), aspiration (n = 8), metabolic acidosis (n = 8), and hypotension (n = 4). A peak concentration of > 450 microg/mL was more likely to be associated with a moderate or major adverse outcome (p < 0.005). A peak concentration > 850 microg/mL was more likely to be associated with coma (p < 0.005) and acidosis (p < 0.005). Eleven patients experienced transient thrombocytopenia (platelets < 150,000) and all had peak valproic acid concentrations >450 microg/mL. Four patients experienced transient leukopenia (WBC < 3,500). The mean hospital stay for all patients was 42 +/- 33.1 hours. A hospital stay > 48 hours was more likely to be associated with a peak valproic acid concentration > 450 microg/mL (p < 0.05). There were 2 fatalities. CONCLUSIONS: In this case series, patients with peak valproic acid concentrations above 450 microg/mL were more likely to develop significant clinical effects and have longer hospital stays. A peak valproic acid concentration above 850 microg/mL was more likely to be associated with coma, respiratory depression, aspiration, or metabolic acidosis. PMID- 11192463 TI - A method for detecting current temporal clusters of toxic events through data monitoring by poison control centers. AB - BACKGROUND: Poison control centers have become a widely recognized source of data for chemical and other environmental exposures. Concurrently, increased emphasis on early identification of temporal clustering of toxic exposures has stimulated development of sensitive statistical methods to detect clusters at the time of occurrence. METHOD: This paper discusses the scan test which has been applied to retrospective data to detect carbon monoxide poisoning clusters. We propose a more sensitive method, based on the binomial distribution to detect current clusters of only 1 or more days duration during the ongoing data collection and monitoring process. RESULTS: Applied to daily carbon monoxide poisoning incidence data on which the scan test has been applied, the new test for current clustering evidently has much more power. For retrospective identification of previous clusters lasting more than 1 day, the scan test is recommended. However, for previous daily clusters, a third method is recommended. CONCLUSION: Certain toxic events such as carbon monoxide poisoning occasionally occur in daily clusters, or in clusters lasting a few days. Timely detection of clusters requires application of early intervention strategies fostered by sensitive statistical methods of detection, as presented here. PMID- 11192464 TI - Thallium poisoning during pregnancy: a case report and comprehensive literature review. AB - BACKGROUND: Thallium salts were once used to treat a variety of disorders such as tuberculosis, sexually transmitted diseases, and ringworm of the scalp. Although the clinical manifestations and treatment of patients with thallium poisoning are well characterized, little information is available on the outcome of pregnancy in thallium-poisoned women. A case of thallium poisoning that began during the first trimester of pregnancy and resulted in fetal demise is reported. METHODS: An extensive literature search identified reported cases of thallium poisoning during pregnancy from 1903 until the present time. All articles were obtained, translated, and abstracted using a standardized data collection form. References were hand-searched and abstracted to identify additional cases. RESULTS: From a total of 25 cases identified, only 18 met satisfactory criteria for inclusion. Five exposures occurred during the first trimester, 5 during the second trimester, and 8 during the third trimester. Mothers developed classic signs and symptoms of thallium poisoning. Summary of these cases demonstrates a range of fetal effects from severe toxicity with residual sequelae to outwardly normal development. Interestingly, some newborns appeared normal despite severe maternal toxicity. The only consistent effect identified was a trend toward prematurity and low birth weight in children exposed during early gestation. CONCLUSIONS: These cases document the transfer of thallium both across the placenta and in breast milk. Insufficient data are available to evaluate prognostic markers of fetal outcome, or the risks and benefits of various treatment regimens in pregnant patients with thallium poisoning. PMID- 11192465 TI - Recovery from severe arsenic-induced peripheral neuropathy with 2,3-dimercapto-1 propanesulphonic acid. AB - CASE REPORT: A 33-year-old female with a 1.5-year history of multisystem illness was diagnosed with arsenic poisoning. Twenty-four-hour urine arsenic was 1030 microg/dL (normal 0-99) and root hair arsenic was 130 microg/g (normal 0-3). Despite treatment with succimer meso-2,3-dimercaptosuccinic acid, her neuropathy progressed to ventilator dependence and quadriplegia. Subsequent intravenous treatment with 2,3-dimercapto-1-propanesulfonic acid sodium salt was associated with arsenic diuresis, marked neuropathic improvement, and extubation. At 1-year follow-up, neuropathy was limited to mild distal lower extremity weakness and sensory loss. The use of 2,3-dimercapto-1-propanesulphonic acid in the treatment of severe arsenic neuropathy was associated with increased urinary elimination of arsenic and dramatic clinical recovery. PMID- 11192466 TI - Mephenytoin overdose--phenytoin poisoning incognito? Case report and mephenytoin/phenytoin comparison. AB - BACKGROUND: Unlike phenytoin, overdose from mephenytoin (CAS No. 50-12-4) is rare. A review of mephenytoin shows a number of differences from phenytoin, including structural, metabolic, pharmacodynamic, and toxicologic effects. Mephenytoin metabolism is also characterized by genetic polymorphism, which can result in prolonged elimination. Routine blood testing for phenytoin may show no interference from mephenytoin. Mephenytoin levels are not readily available nor clinically useful when they do become available; urine toxicology screen may be positive for barbiturates. CASE REPORT: A 26-year-old female overdosed on approximately 12 g of mephenytoin and an unknown amount of valproic acid. She became comatose, developing pulmonary aspiration and pancreatitis with fever. Her Intensive Care Unit treatment was prolonged with slow resolution over 10 days. A review of mephenytoin and comparison to phenytoin overdose is provided in the context of this case report. PMID- 11192467 TI - Butoxyethanol ingestion with prolonged hyperchloremic metabolic acidosis treated with ethanol therapy. AB - BACKGROUND: Severe toxic ingestions of butoxyethanol (CAS No. 111-76-2) are rare despite the prevalence of this glycol ether in products such as glass and surface cleaners. Manifestations of acute butoxyethanol toxicity include metabolic acidosis, hemolysis, hepatorenal dysfunction, and coma, but vary widely in reported cases. Furthermore, the optimal therapeutic approach is not yet established. Much of the toxicity of butoxyethanol has been ascribed to its aldehyde and acid metabolites which are similar to those produced by oxidative metabolism of methanol and ethylene glycol. Although the roles of alcohol dehydrogenase inhibition with ethanol or fomepizole and hemodialysis are clear in the case of toxic ingestions of methanol and ethylene glycol, they remain poorly defined for butoxyethanol poisoning. CASE REPORT: We report the case of a 51-year old female who ingested up to 8 ounces of Sanford Expo White Board Cleaner (butoxyethanol and isopropanol). She developed prolonged hyperchloremic metabolic acidosis and mental status depression and was treated with ethanol therapy but not hemodialysis. This patient recovered without apparent sequelae. The kinetics of butoxyethanol metabolism in this case are described and the potential therapeutic options are discussed. PMID- 11192468 TI - Nystagmus secondary to fomepizole administration in a pediatric patient. AB - BACKGROUND: Fomepizole is an alcohol dehydrogenase inhibitor used to treat ethylene glycol poisoning in adults, with only one report describing the use of fomepizole in the pediatric population. We report a case of nystagmus associated with fomepizole treatment of a 6-year-old female who ingested ethylene glycol 15 hours prior to admission. CASE REPORT: A previously healthy 6-year-old presented to the emergency department mottled, comatose, and with Kussmaul respirations. Initial arterial blood gases: pH 7.11, PO2 200, HCO3 2, base excess -29, and within 20 minutes her pH dropped to 7.03. The patient was responsive to pain only. Initially, crystalluria without fluorescence was observed in the emergency department; 2 hours after admission, the urine fluoresced under Wood's light. Laboratory data were significant for increased anion and osmolar gaps. She was fluid-resuscitated, NaHCO3, thiamine, and pyridoxine were administered, and she was admitted to the pediatric intensive care unit. Within 4 hours of admission, a loading dose of fomepizole (15 mg/kg) was infused due to the severity of the patient's clinical status. Hemodialysis was initiated but discontinued temporarily due to catheter thrombus formation. The initial (3-hour postadmission) ethylene glycol concentration was 13 mg/dL. She developed coarse vertical nystagmus within 2 hours of fomepizole infusion. The ethylene glycol concentration was 5 mg/dL 3 hours after hemodialysis which then was discontinued. No further fomepizole was administered and the child recovered uneventfully. CONCLUSION: There was no evidence of the more frequently cited adverse events, such as headache, nausea, and dizziness. Fomepizole has been incompletely evaluated in the pediatric population, and the nature and occurrence of adverse events have not been described adequately. The use of fomepizole appeared safe in this patient although she developed transient nystagmus. PMID- 11192469 TI - Central nervous system toxicity and early peripheral neuropathy following dermal exposure to methyl bromide. AB - CASE REPORT: We describe a case of early peripheral neuropathy and central nervous system toxicity as a result of acute predominantly dermal exposure to methyl bromide. A 32-year-old male was admitted after an accidental predominantly dermal exposure to methyl bromide while fumigating soil for pest control. The patient suffered dermal burns and vesicles on the upper and lower limbs. One week following exposure, he developed progressive weakness of the lower limbs, ataxia, paresthesiae of both legs and the left arm, hyperactive tendon reflexes in the lower limbs, and left Babinski sign. Nerve conduction velocity testing was compatible with axonal neuropathy. The patient recovered gradually from his burns. Three months postexposure he showed no signs of central nervous system toxicity, but the peripheral neuropathy was still present. DISCUSSION: Neurological effects primarily referable to the central nervous system following severe inhalation of methyl bromide have frequently been reported. The patient described in this study developed an unusual early peripheral neuropathy following dermal exposure. Peripheral neuropathy can be an outcome of methyl bromide intoxication, but is usually a late sequela of acute central nervous system toxicity or an aftereffect of repetitively inhaled chronic exposure. In this case, exposure to methyl bromide through abraded skin caused early peripheral neuropathy and central nervous system toxicity. PMID- 11192470 TI - Intoxication with huperzine A, a potent anticholinesterase found in the fir club moss. AB - BACKGROUND: Herbs from Lycopodium are generally reputed to be nontoxic and are occasionally used for preparing a salubrious tea. In Europe, the common Lycopodium clavatum can be easily confused with Lycopodium selago, the fir club moss. CASE REPORT: We report 2 patients who drank a tea, erroneously prepared from dried herbs of Lycopodium selago, which resulted in sweating, vomiting, diarrhea, dizziness, cramps, and slurred speech. These symptoms were suggestive of a cholinergic mechanism. To elucidate the active principle, aqueous extracts of Lycopodium selago were checked for their suspected anticholinesterase activity using human erythrocytes as an enzyme source in a modified Ellman assay. The extracts did exhibit significant anticholinesterase activity. The anticholinesterase(s) were most effectively extracted with dichloromethane and isolated by high-performance liquid chromatography. The major compound with anticholinesterase activity co-chromatographed with authentic huperzine A, but had a 2-3-fold higher inhibitory potency than the racemic standard. The amount of huperzine A found in the Lycopodium selago sample used for the tea preparation was calculated to be sufficient for a relevant acetylcholinesterase inhibition. CONCLUSION: The signs and symptoms of Lycopodium selago poisoning are consistent with the anticholinesterase activity of huperzine A and should favorably respond to atropine therapy. This report demonstrates once more that laymen should not be encouraged to gather their remedies from "Mother Nature" without advanced botanical knowledge. PMID- 11192471 TI - Apparent suicide with Renewtrient. PMID- 11192472 TI - The role of population pharmacokinetics in drug development in light of the Food and Drug Administration's 'Guidance for Industry: population pharmacokinetics'. AB - Population pharmacokinetics (PPK) has evolved from a discipline primarily applied to therapeutic drug monitoring to one that plays a significant role in clinical pharmacology in general and drug development in particular. In February 1999 the US Food and Drug Administration issued a 'Guidance for Industry: Population Pharmacokinetics' that sets out the mechanisms and philosophy of PPK and outlines its role in drug development. The application of PPK to the drug development process plays an important role in the efficient development of safe and effective drugs. PPK knowledge is essential for mapping the response surface, explaining subgroup differences, developing and evaluating competing dose administration strategies, and as an aid in designing future studies. The mapping of the response surface is done to maximise the benefit-risk ratio, so that the impact of the input profile and dose magnitude on beneficial and harmful pharmacological effects can be understood and applied to individual patients. PPK combined with simulation methods provides a tool for estimating the expected range of concentrations from competing dose administration strategies. Once extracted, this knowledge can be applied to labelling or used to assess various future study designs. PPK should be implemented across all phases of drug development. For preclinical studies, PPK can be applied to allometric scaling and toxicokinetic analyses, and is useful for determining 'first time in man' doses and explaining toxicological results. Phase I studies provide initial understanding of the structural model and the effect of possible covariates, and may later be used to evaluate PPK differences between patients and healthy individuals. Phase II studies provide the greatest opportunity to map the response surface. With these PPK models it is possible to gain an improved understanding of the role of the dose on the response surface and of the range of expected responses. In phase III and IV studies, PPK is implemented to further refine the PPK model and to explain unexpected responses. Planning for the implementation of PPK across all phases of drug development is necessary, as well as planning for individual PPK studies. Planning should include: defining important questions, identifying covariates and drug-drug interactions that need to be investigated, and identifying the applications and intended use of the model(s). The plan for each project must have a strategy for data management, data collection, data quality assurance, staff training for data collection, data analysis and model validation. PMID- 11192473 TI - Clinical pharmacokinetics of pravastatin: mechanisms of pharmacokinetic events. AB - Pravastatin, one of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) widely used in the management of hypercholesterolaemia, has unique pharmacokinetic characteristics among the members of this class. Many in vivo and in vitro human and animal studies suggest that active transport mechanisms are involved in the pharmacokinetics of pravastatin. The oral bioavailability of pravastatin is low because of incomplete absorption and a first-pass effect. The drug is rapidly absorbed from the upper part of the small intestine, probably via proton-coupled carrier-mediated transport, and then taken up by the liver by a sodium-independent bile acid transporter. About half of the pravastatin that reaches the liver via the portal vein is extracted by the liver, and this hepatic extraction is mainly attributed to biliary excretion which is performed by a primary active transport mechanism. The major metabolites are produced by chemical degradation in the stomach rather than by cytochrome P450 dependent metabolism in the liver. The intact drug and its metabolites are cleared through both hepatic and renal routes, and tubular secretion is a predominant mechanism in renal excretion. The dual routes of pravastatin elimination reduce the need for dosage adjustment if the function of either the liver or kidney is impaired, and also reduce the possibility of drug interactions compared with other statins. which are largely eliminated by metabolism. The lower protein binding than other statins weakens the tendency for displacement of highly protein-bound drugs. Although all statins show a hepatoselective disposition, the mechanism for pravastatin is different from that of the others. There is high uptake of pravastatin by the liver via an active transport mechanism, but not by other tissues because of its hydrophilicity, whereas the disposition characteristics of other statins result from high hepatic extraction because of high lipophilicity. These pharmacokinetic properties of pravastatin may be the result of the drug being given in the pharmacologically active open hydroxy acid form and the fact that its hydrophilicity is markedly higher than that of other statins. The nature of the pravastatin transporters, particularly in humans, remains unknown at present. Further mechanistic studies are required to establish the pharmacokinetic-pharmacodynamic relationships of pravastatin and to provide the optimal therapeutic efficacy for various types of patients with hypercholesterolaemia. PMID- 11192474 TI - Clinical pharmacokinetics of reboxetine, a selective norepinephrine reuptake inhibitor for the treatment of patients with depression. AB - Reboxetine is a novel selective norepinephrine inhibitor that has been evaluated in the treatment of patients with depression. Reboxetine is a racemic mixture, and the (S,S)-(+)-enantiomer appears to be the more potent inhibitor. However, the ratio of the areas under the concentration-time curves of the (S,S)-(+)- and (R,R)-(-)-enantiomers in vivo is approximately 0.5. There is no evidence for chiral inversion. Differences in the clearances of the 2 enantiomers may be explained by differences in protein binding. The pharmacokinetics of reboxetine are linear following both single and multiple oral doses up to a dosage of 12 mg/day. The plasma concentration-time profile following oral administration is best described by a 1-compartment model, and the mean half-life (approximately 12 hours) is consistent with the recommendation to administer the drug twice daily. Reboxetine is well absorbed after oral administration. The absolute bioavailability is 94.5%, and maximal concentrations are generally achieved within 2 to 4 hours. Food affects the rate, but not the extent, of absorption. The distribution of reboxetine appears to be limited to a fraction of the total body water due to its extensive (>97%) binding to plasma proteins. The primary route of reboxetine elimination appears to be through hepatic metabolism. Less than 10% of the dose is cleared renally. A number of metabolites formed through hepatic oxidation have been identified, but reboxetine is the major circulating species in plasma. In vitro studies show that reboxetine is predominantly metabolised by cytochrome P450 (CYP) 3A4; CYP2D6 is not involved. Reboxetine plasma concentrations are increased in elderly individuals and in those with hepatic or renal dysfunction, probably because of reduced metabolic clearance. In these populations, reboxetine should be used with caution, and a dosage reduction is indicated. Ketoconazole decreases the clearance of reboxetine, so that the dosage of reboxetine may need to be reduced when potent inhibitors of CYP3A4 are coadministered. Quinidine does not affect the in vivo clearance of reboxetine, confirming the lack of involvement of CYP2D6. There is no pharmacokinetic interaction between reboxetine and lorazepam or fluoxetine. Reboxetine at therapeutic concentrations has no effect on the in vitro activity of CYP1A2, 2C9, 2D6, 2E1 or 3A4. The lack of effect of reboxetine on CYP2D6 and CYP3A4 was confirmed by the lack of effect on the metabolism of dextromethorphan and alprazolam in healthy volunteers. Thus, reboxetine is not likely to affect the clearance of other drugs metabolised by CYP isozymes. PMID- 11192475 TI - Clinical and preclinical pharmacokinetics of raltitrexed. AB - Raltitrexed is a specific, folate-based inhibitor of thymidylate synthase with activity in advanced colorectal cancer comparable with that of fluorouracil (5 fluorouracil) plus folinic acid. Its activity is enhanced by rapid cellular entry and polyglutamation, with the polyglutamated derivatives having approximately 100 fold greater inhibitory potency than the parent compound. A number of phase I/pharmacokinetic studies have been performed, including schedules involving a 15 minute infusion every 3 weeks, weekly x 6 every 8 weeks, and every 2 weeks. The maximum tolerated dose (MTD) for the 3-weekly schedule was 3.5 to 4.5 mg/m2 in adults and 6 mg/m2 in a paediatric population. The MTDs for the other schedules have not yet been reported. The disposition of raltitrexed in patients is best described by a 3-compartment model with a terminal half-life (t1/2gamma) of 260 hours, the latter being subject to significant interpatient variability. A similar protracted t1/2gamma has been detected in all of the animal species studied. Together with evidence from the mass-balance studies performed, this delayed elimination suggests considerable sequestration of raltitrexed in tissues, predominantly as polyglutamate forms. Nevertheless, there has been no pharmacokinetic evidence of drug accumulation in plasma following repeated administration. On the basis of animal experiments, the oral bioavailability and penetration of raltitrexed into cerebrospinal fluid are both likely to be limited in the clinical setting. Raltitrexed is over 90% bound to plasma protein over the concentration range of 20 to 100 micromol/L. Apart from poly-glutamation, raltitrexed does not appear to be metabolised to a significant extent, and most of the excreted drug (approximately 20% of the administered dose) is recovered unchanged in the urine within the first 24 hours post-administration. The average clearance of raltitrexed is 2.4 L/h (40 ml/min), and this value is significantly reduced in patients with compromised renal function (glomerular filtration rate of 25 to 65 ml/min). These patients are more likely to experience severe antiproliferative toxicity with raltitrexed. A careful evaluation of renal function, particularly in the elderly, is warranted. It has not been possible to establish strong correlations between the plasma pharmacokinetics of raltitrexed and toxicity, and the cellular pharmacokinetics of raltitrexed may be more predictive. Studies in mice have demonstrated that delayed administration of folinic acid can assist in the recovery of animals from antiproliferative toxicity, possibly by promoting the release of polyglutamated drug from tissues. This approach should be evaluated as a rescue regimen in patients with severe proliferative toxicity. PMID- 11192476 TI - Monitoring antiplatelet therapy: What is the best method? AB - Platelet function tests measure different aspects of platelet function, which include adherence, activation, aggregation and secretion. Clinically, the goal of platelet function testing is to provide information about the platelet contribution to the risk of thrombotic or haemorrhagic events and the optimisation of antiplatelet therapy. The important clinical questions are whether an antiplatelet agent is having the desired effect on platelet inhibition (effectiveness) and whether the patient has sufficient residual platelet function to avoid bleeding (safety). The role of aspirin (acetylsalicylic acid) and thienopyridines is well established in the management of patients with coronary artery disease and in the setting of coronary interventions. The last several years have demonstrated the unequivocal effectiveness of intravenously administered platelet glycoprotein (GP) IIb/IIIa antagonists in the management of acute coronary syndromes and in the setting of percutaneous coronary interventions. With the increasing use of these GPIIb/IIIa antagonists, it is becoming more important clinically to measure platelet inhibition with these agents. This paper reviews major techniques and instrumentation for platelet monitoring and discusses the goals of the best method. PMID- 11192478 TI - Dump the data dump. PMID- 11192477 TI - Chiral bioequivalence: effect of absorption rate on racemic etodolac. AB - BACKGROUND: For many racemic drugs, bioequivalence assessment based on isomer nonspecific assays is appropriate because enantiomeric area under the concentration-time curve (AUC) exposure ratios are close to unity. Use of nonspecific methods in cases in which the ratio is substantially greater or less than 1, however, may obscure real therapeutic differences among formulations, especially if the enantiomers exhibit differing pharmacological potencies. OBJECTIVE: To examine the influence of absorption rate on etodolac bioequivalence as measured by total [(R,S)-] and (S)-etodolac. DESIGN: Single dose, 3-period, crossover, pharmacokinetic study in 24 healthy volunteers in which the administration rate of etodolac was varied. METHODS: Participants received etodolac 400mg in solution, given as a single dose over 1 minute or as divided doses over 30 and 90 minutes. Unresolved and enantiomer concentrations of etodolac were measured by a validated HPLC assay. The enantiomer ratio was similarly measured by HPLC. RESULTS: Bioequivalence parameters derived for both unresolved and (S)etodolac indicate that peak plasma drug concentration (Cmax) was not bioequivalent. By delaying absorption, bioequivalence was lost. CONCLUSIONS: Collectively, these data demonstrate that bioequivalence between 2 products of etodolac based on enantiomerically nonspecific criteria alone may not generalise to the pharmacologically relevant (S)-enantiomer. This suggests that enantiospecific assays are necessary for bioequivalence assessments. PMID- 11192479 TI - Getting started. Interview by Jeffrey C. Bates and M. Walt Carroll. PMID- 11192480 TI - MedBytes. PMID- 11192481 TI - Second-quessing the insurers. PMID- 11192482 TI - Politics versus policies. PMID- 11192483 TI - Redistricting: where politicians eat their young. PMID- 11192484 TI - Paper tiger. PMID- 11192485 TI - Unhealthy children. PMID- 11192486 TI - Saving country doctors. PMID- 11192487 TI - Physician assistants in Texas. AB - Understanding the health requirements of a state begins with identifying the population at need and the workforce available to meet those needs. A descriptive study was undertaken to examine the physician assistant (PA) workforce in Texas as part of an ongoing effort to meet the health needs of Texas residents. In September 2000, Texas had 2237 licensed PAs practicing in 186 counties. Education for PAs in Texas began in 1970 and currently includes one private, one military, and six public programs. Most practicing PAs in Texas graduate from in-state programs and tend to locate within the state. Preparations are under way to shift the public undergraduate programs to graduate degree programs. Although barriers to health care access in Texas remain a substantial public health issue, PAs have helped reduce these barriers, especially in many rural communities. The supply of and demand for Texas PAs appear to be in equilibrium. Policy implications are discussed. PMID- 11192488 TI - Congress, legislature facing tough issues. PMID- 11192489 TI - Efficacy of sulphasalazine plus methotrexate in rheumatoid arthritis. AB - Early intervention with slow acting anti-rheumatic drugs (SAARDs) has led to improvement in substantial proportion of rheumatoid arthritis (RA) patients. The present open, controlled study was designed to assess whether a combination of SAARDs offer any added benefit. Fifty-four adult RA patients were randomly allocated to methotrexate (MTX) (n = 27) and MTX plus sulphasalazine (SSZ) (n = 27) groups. The subjects were followed-up fortnightly for four weeks then monthly for six months. The disease activity was assessed with the help of 10 clinical and four laboratory indices. The improvement was graded as: minor, mild decreases in indices, non-steroidal anti-inflammatory drugs (NSAIDs) continued, physician's global assessment (PGA) decreased by one; marked, acceptable decreases in indices, NSAIDs being taken sparingly, PGA decreased by at least 2, and complete, all indices normalised and patients discontinued NSAIDs completely. The improvement was considered clinically important when marked or complete improvement occurred. Adverse drug reactions resulted in withdrawal of 4 subjects from the MTX + SSZ group and 1 from the control groups. Four and three subjects in the combined and MTX groups respectively were lost to follow-up. Subjects in both groups showed significant decline in all indices except hemoglobin and neutrophil count. The differences between the two groups in the pre-treatment and post-treatment values were insignificant. Complete, marked, minor and no improvement occurred in 4 (21%), 12 (63%), 3 (16%) & 0 in the MTX and in 11 (48%), 7 (30%), 4 (17%) & 1 (4%) in MTX + SSZ groups respectively. The differences in the rates of complete and clinically important improvement between the two groups were insignificant (P 0.1398 and 0.7092). The incidence of side effects was insignificantly higher in the MTX + SSZ group. Most of them were mild and transient. The combination of SAARDs offered little added advantage in RA. However, the higher rate of complete improvement in the combination group justifies trials including larger samples. PMID- 11192490 TI - Serological response to immunization with tetanus toxoid. AB - A total of two hundred women were immunized with tetanus toxoid vaccine. Two batches of toxoid prepared at the Institute of Public Health (IPH), Dhaka and one batch of imported vaccines, were being used by the EPI in Bangladesh for immunization. Each hundred women were immunized by IPH and imported vaccine. Two human doses were given in one month interval. Blood samples from all the study subjects were collected on the day of 1st dose and one month after second dose. Both the preimmunized sera and the sera after vaccination were tested to determine the antibody titre against tetanus toxoid by the haemagglutination method. The preimmunized sera showed the presence of protective antibody in 50(25%) subjects who had the history of previous immunization. Including these initial antitoxin positive cases the seroconversions found among 95% and 96% of the study population respectively after immunization with IPH and imported toxoids, which were 93.05% and 94.87% when these 50 subjects were excluded. No significant difference (p = 1.0) was observed between the immunity of the subjects after receiving IPH and imported vaccine. Antibody titre of initial tetanus-antitoxin positive cases raised eight folds after getting more doses. The result gave fair indication of the antigenicity of all the toxoids used in the study. PMID- 11192491 TI - Characterisation of Jack fruit lectin. AB - Jack fruit (Artocarpus Heterophyllus) seed extract contains a lectin termed Jack fruit lectin (JFL) which possesses diversed biological properties. A detailed analysis of its properties has been lacking. The present investigation was initiated to study the detail properties of JFL. After extraction and purification on affigel galactosamine-agarose column, JFL was subjected to ND PAGE. Several different charged species from ND-PAGE upon SDS-PAGE gave rise to two dissimilar trimeric subunit at 12.5 and 15.0 KDa and retain biological activity. It was possible to elute the subunit bands separately from polyacrylamide gel to investigate their biological activity. Each subunit was found to be retained the lectin activity. Agglutinating activity of smaller subunit was found to be more, may be due to the greater amount of the subunit. This also suggests that each unit of trimeric JFL have similar lectin activity. PMID- 11192492 TI - Isolation modifies the behavioural response in rats. AB - Twenty-four male wister rats were reared from weaning either alone (isolation reared) or in groups of five (socially reared) for 6 weeks. Thereafter, the present study examined and compared the behaviour of isolation and socially reared rats in the test of social interaction, in the elevated plus-maze test of anxiety, in the open field behavior of exploration and locomotion activity, and the depressive behaviour in forced swim test. Under high light in unfamiliar conditions isolation reared rats spent significantly more time in aggressive interactions (P < 0.05) and high levels of aggressive behaviour compared to the socially reared rats (P < 0.05). Isolation reared rats had spent less time in the open arms than the socially reared rats in the maze test (P < 0.05). Isolation reared rats were more exploratory than the socially reared rats in the open field test and the defaecation scores were less compared to the socially reared controls (P < 0.05). Isolated rats spent less time immobile on the rats' forced swim test behaviour but the difference was not statistically significant. These findings suggest that isolation reared rats are nervous, aggressive and hyperactive animals in a novel field. It appears that isolation rearing in the early stages of life has modified a variety of behaviour in the adult rats, and the investigation of the pattern of behavioural changes in isolation reared rats may help to explore the environmental influences on the development of human psychopathology. PMID- 11192493 TI - Lymphoscintigraphy in staging and management of breast cancer. AB - Internal mammary lymphoscintigraphy (IML) is a simple non-invasive and reproducible technique to determine the extent of the parasternal node invasion in patients suffering from breast cancer. A total forty four patients--37 before surgery or any sort of treatment and seven patients after having undergone surgery, chemotherapy and/or radiotherapy were included in this study to assess the potential role of lymphoscintigraphy in the context of the present 'state of the art' of staging and management of breast cancer patients in Bangladesh. The scintigraphic test was done using Technetium 99m (Tc-99m) Antimony sulfide colloid in a dose of 500 microCi injected interstitially into the sub-costal space. Images were obtained after two to three hours on a Gamma Camera and the study findings were then interpreted as normal, abnormal and equivocal. The scintigraphic images obtained in patients who had undergone surgery, chemotherapy and/or radiotherapy were difficult and more challenging to interpret than those images obtained from patients before surgery or other therapy. This was evidenced by the high number (71%) equivocal cases of IML findings in patients after treatment as compared to only 22% equivocal cases in patients studied before surgery or other therapy. Parasternal lymph node involvement was found to occur regardless of the site or size of the primary tumour. Thirty three percent of tumours located in the outer quadrant showed abnormal nodes on IML. When the size was considered, IML was found abnormal in 22.20% patients with tumour size less than 2 cm in diameter. Correlation of IML with clinically palpable lymph nodes showed abnormal scan findings in 18% patients without clinically demonstrable axillary lymph nodes. These findings are in agreement with previously published data and suggests that conventionally classified stage I patients may in effect be in stage II or even in stage III of the disease. In conclusion, when the technique of lymphoscintigraphy is done with a comprehensive overview of the patient, and when the interstitial injection site is correct, it will generally lead to a logical and clinically useful interpretation of the data for more efficient management of the patient with breast cancer. PMID- 11192494 TI - Winston R. Maxted and the type specificity of group A streptococci. PMID- 11192495 TI - Primary brain abscess with Nocardia otitidiscaviarum in an intravenous drug abuser. AB - A primary brain abscess with Nocardia otitidiscaviarum in an intravenous drug abuser is reported. Nocardia brain abscess has been reported infrequently and normally only in immunocompromised patients. The lungs are the most common primary focus, but brain abscess may also occur following direct cutaneous inoculation. In this case the clinical presentation was first diagnosed as an astrocytoma. However, N. otitidiscaviarum was isolated from the lesion after emergency craniotomy. In contrast to five cases described previously the patient survived after surgical removal and antibiotic treatment with imipenem and trimethoprim-sulphamethoxazole. PMID- 11192496 TI - Increases in the mutation frequency at which fusidic acid-resistant Staphylococcus aureus arise with salicylate. AB - Salicylate was shown to increase the frequency at which a fusidic acid susceptible strain of Staphylococcus aureus underwent mutation to become fusidic acid-resistant. These fusidic acid-resistant mutants had alterations in spectinomycin and kanamycin resistance levels indicative of mutations in fusA, the gene that encodes elongation factor-G, the target of fusidic acid. PMID- 11192497 TI - A clinical isolate of Bacteroides fragilis from Hungary with high-level resistance to imipenem. PMID- 11192498 TI - Gellan gum as a suitable gelling agent in microbiological media for PCR applications. PMID- 11192499 TI - Immunogeneity and structural organisation of some pLCR-encoded proteins of Yersinia pestis. AB - A novel method of cultivation of Yersinia pestis EV-76 and its isogenic strains KM-217 (pPst-;pCad+;pFra-) and KM-218 (pPst-;pCad-;pFra-) and careful extraction of Y. pestis proteins (YPPs) permitted isolation of >35 low Ca2+ response plasmid (pLCR)-encoded products, some of which are potentially new members of the LCR family. Immunisation with each YPP demonstrated that 25-, 54-, 72- and 87-kDa YPPs provided the highest level of protection in mice challenged with Y. pestis virulent strain 231. Their immunological relationship was established with monoclonal antibodies (MAbs) and revealed several common properties, including oligosaccharide binding with specificity for N-acetylglucosamine. Affinity chromatography with MAb to the 25-kDa YPP permitted purification of the relevant antigen and its precursor. Their existence in the form of a complicated protein molecule was shown. PMID- 11192500 TI - Binding of alpha2-laminins by pathogenic and non-pathogenic mycobacteria and adherence to Schwann cells. AB - The ability of Mycobacterium leprae to specifically bind alpha2-laminins of Schwann cells has been described recently as being an important property of the leprosy bacillus, which could explain the neural tropism of M. leprae. Therefore, the extent of the expression of alpha2-laminin-binding properties among mycobacteria was investigated. In an ELISA-based assay, all three species of Mycobacterium tested (M. tuberculosis, M. chelonae and M. smegmatis) expressed laminin-binding capacity, suggesting that the ability to bind alpha2-laminins is conserved within the genus Mycobacterium. This report also demonstrated that not only M. leprae but all the mycobacterial species tested readily interacted with the ST88-14 cells, a human schwannoma cell line, and that the addition of soluble alpha2-laminins significantly increased their adherence to these cells. These results failed to demonstrate the presence in M. leprae of a unique system based on alpha2-laminins for adherence to Schwann cells. PMID- 11192501 TI - Molecular analysis of clinical isolates of Providencia alcalifaciens. AB - In an attempt to elucidate the virulence factors and the pathogenic mechanisms of Providencia alcalifaciens, 36 isolates identified in 1994-1995 in Recife city, Brazil were analysed by PCR to investigate the presence of DNA sequences homologous to virulence genes described in other invasive enterobacteria, as well as their ability to invade HeLa cells, their plasmid profiles and antibiotic resistance patterns. The genetic diversity of the isolates was also analysed by RAPD-PCR. No homologous sequences of virulence genes were observed with any of the P. alcalifaciens isolates studied. Ten isolates had no plasmid and 26 harboured one-to-five plasmids of 147-<6.9 kb. Invasion of HeLa cells was observed in only 10 isolates. No correlation between the plasmid content of the strains, their invasion of HeLa cells or their resistance to antimicrobial drugs could be established. The isolates could be distributed into 10 genotypic groups by RAPD-PCR. Considering the genotypic profile and ability to invade HeLa cells, 7 of the 10 invasive isolates belonged to the same genotypic group. The presence of invasive isolates in the same or a related genotypic group suggests the existence of a clonal lineage responsible for the invasiveness. PMID- 11192502 TI - Involvement of staphylococcal protein A and cytoskeletal actin in Staphylococcus aureus invasion of cultured human oral epithelial cells. AB - Following the coincidental discovery that beta-actin isolated from renal epithelial cells was precipitated by staphylococcal protein A (SPA), the possibility that SPA and cytoskeletal actin filaments may be involved in Staphylococcus aureus infection of epithelial cells was considered. Therefore, to clarify the potential role of SPA and actin filaments in S. aureus infection, the invasion efficiency of S. aureus was determined quantitatively by measuring the number of cfu of viable organisms recovered from cultured KB cells. S. aureus invasion was found to be time dependent (0-60 min) and increased linearly when increasing numbers of bacteria were added (10(4)-10(6) cfu/ml). However, significant variation in the level of invasion was noted in protein A-deficient S. aureus Wood 46. Cytochalasin B inhibited the invasion efficiency of S. aureus in a dose-dependent manner. The present study suggests that interaction of staphylococcal protein A and cytoskeletal actin filaments is involved in the S. aureus invasion of cultured KB cells, and this process may contribute, in part, to the intracellular movement, cell-to-cell spread and dissemination of S. aureus within human oral epithelial cells in vivo. PMID- 11192503 TI - Induction of necrosis factor-alpha and interleukin-6 in mice in vivo and in murine peritoneal macrophages and human whole blood cells in vitro by Micrococcus luteus teichuronic acids. AB - Earlier studies showed that Micrococcus luteus cells and cell walls induced anaphylactoid reactions leading to death, in some instances within 1 h, in C3H/HeN mice primed with muramyl dipeptide (MDP). They also induced serum cytokines in the surviving mice. The present study investigated the structural components responsible for these activities. Teichuronic acids, a component of M. luteus cell walls, induced tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in MDP-primed C3H/HeN mice. Peptidoglycans had little effect on the cytokine-inducing activities. Reducing teichuronic acids, i.e., teichuronic acids whose carboxyl groups had been reduced, lost their cytokine inducing activities. Neither peptidoglycans nor teichuronic acids induced anaphylactoid reactions in the MDP-primed mice. Purified teichuronic acids also induced TNF-alpha and IL-6 production in C3H/HeN murine peritoneal macrophages and human whole-blood cells in the culture, but reduced teichuronic acids did not. The purified teichuronic acids induced no TNF-alpha and only low levels of IL-6 in MDP-primed C3H/HeJ mice, and neither cytokine in peritoneal macrophage cultures from C3H/HeJ mice with a single point of mutation in Toll-like receptor 4 (TLR4) gene. These findings suggest that induction of cytokines by teichuronic acids is mainly TLR4-dependent. PMID- 11192504 TI - The sensitivity of Porphyromonas gingivalis and Fusobacterium nucleatum to different (pseudo)halide-peroxidase combinations compared with mutans streptococci. AB - Previous studies have shown that the peroxidase system with iodide is particularly effective against Actinobacillus actinomycetemcomitans. In the present study, the effects of iodide, chloride and thiocyanate in combinations with lactoperoxidase (LP) and myeloperoxidase (MP) on the viability of Porphyromonas gingivalis, Fusobacterium nucleatum, Streptococcus mutans and S. rattus were analysed. Bacteria were incubated in buffer solution containing peroxidase, substrate(s) and H2O2 (all in oral physiological concentrations), and plated after 0, 0.5 and 1 h. The oxidation product of iodide was the most bactericidal against all the bacteria tested. The effect was significantly weaker on mutans streptococci. Physiological concentrations of thiocyanate abolished the effects of LP-H2O2-iodide and MP-H2O2-iodide/chloride combinations. Thiocyanate peroxidase systems have already been used in oral hygiene products. The incorporation of iodide into these products could make them much more potent against periodontal pathogens, and also help to prevent transmission of these pathogens from person to person via saliva. PMID- 11192505 TI - Reduced bactericidal activity against Staphylococcus aureus and Pseudomonas aeruginosa of blood neutrophils from patients with early adult respiratory distress syndrome. AB - This study investigated the bactericidal capability of circulating neutrophils from blunt trauma patients admitted to an Intensive Care Unit against Staphylococcus aureus and Pseudomonas aeruginosa. Among those patients, two groups were considered and compared: patients who developed adult respiratory distress syndrome (ARDS) and patients who developed only pneumonia. Peripheral blood samples were drawn as soon as a diagnosis of pneumonia or ARDS was made, followed by the isolation of neutrophil cells and assessment of bacteria phagocytosis and killing. The results demonstrated that in patients with ARDS, phagocytosis and killing efficiency were significantly impaired in comparison with patients with pneumonia and healthy controls. A possible dysregulation of reactive oxygen species production involving the release of humoral mediators in early ARDS may be involved. PMID- 11192506 TI - Distribution of immunoglobulin classes and IgG subclasses against a culture filtrate antigen of Burkholderia pseudomallei in melioidosis patients. AB - The class and subclass distribution of antibody response to the culture filtrate antigen (CFA) of Burkholderia pseudomallei was examined in the sera of 45 septicaemic and 17 localised melioidosis cases and 40 cases clinically suspected of melioidosis and the results were compared with those from high-risk and healthy control groups. The geometric mean titre index (GMTI) values for all classes and subclasses of immunoglobulins examined were higher for sera from the proven and clinically suspected melioidosis cases than for the control groups. However, the highest response in the three patient groups was that of IgG with GMTIs ranging from 219.4 to 291.6 and the lowest was for IgM with GMTIs of 22.5, 24.3 and 28.7. The IgA response was intermediate with GMTIs ranging from 119.2 to 170. The GMTIs were highest for IgG in septicaemic and localised infections and for IgA and IgM in localised infections. As regards IgG subclass distribution, IgG1 and IgG2 were the predominant subclasses produced against the CFA in contrast to IgG3 and IgG4, which were produced in low amounts. None of the sera from the control groups had any significant titres of antibodies. PMID- 11192507 TI - Evaluation of serological markers for the immunodiagnosis of acute acquired toxoplasmosis. AB - The detection of specific IgM antibodies has been the most frequently used serological marker for diagnosing recent toxoplasmosis. However, the persistence of specific IgM antibodies in some patients and the use of tests with a low specificity have complicated the interpretation of serological results when toxoplasmosis is suspected. The purpose of the present study was to determine the value of newer serological techniques in the diagnosis of acute acquired toxoplasmosis. Sixty-four sera, 31 from patients with Toxoplasma gondii infection and 33 from patients with latent infection, were tested. Anti-T. gondii IgA was measured by two antibody capture ELISA tests (Platelia Toxo IgA and ETI-TOXOK A) and an automated direct ELISA (IMx Toxo IgA); all three assays detected antibody levels compatible with a recent infection in sera from all 31 patients with acute toxoplasmosis. However, significant levels of IgA were also detected with high frequency by all three assays in sera from patients with latent infection. IgE antibodies detected by IgE immunosorbent agglutination assay (ISAGA) were present in 26 (84%) of 31 patients with acute toxoplasmosis and in sera from two subjects with latent infection taken >1 year after the beginning of the clinical symptoms of infection. Thirty (97%) of 31 patients with a recent T. gondii infection and 15 (45%) of 33 subjects with latent infection had an AC/HS pattern compatible with acute toxoplasmosis. The avidity of T. gondii IgG was evaluated by two methods. One method was based on the titration of each serum sample and calculation of the titres, in the absence and presence of urea, in relation to a defined cut-off value. In the other method, a single serum dilution was used and the absorbances of the reactions in the presence and absence of urea were compared. The titration method was more sensitive for diagnosing recent primary infection; all 31 sera from patients with acute toxoplasmosis had avidity indices compatible with acute toxoplasmosis by the titration method, whereas with the single dilution method, sera from four patients had equivocal results. In the 33 individuals with latent infection, similar results were obtained with the two avidity methods; only one serum sample had a non-compatible avidity value with the titration method. The results obtained in the present study show that the current serological markers used for diagnosing acute acquired toxoplasmosis have significant limitations. The data suggest that determination of the avidity of T. gondii-specific IgG by the titration method in patients with detectable IgM antibodies defines most accurately the stage of infection by T. gondii. PMID- 11192508 TI - Carriage of class 1 integrons and antibiotic resistance in clinical isolates of Acinetobacter baumannii from northern Spain. AB - A collection of 70 clinical isolates of Acinetobacter baumannii from Bilbao in northern Spain was examined by PCR for the presence of class 1 integron structures. The organisms comprised 21 distinct RAPD genotypes, with 10 distinct antibiogram patterns. Four different integron structures were detected in a total of 59 (84%) of the 70 isolates, with two predominant integron structures found in 20 and 30 isolates each. No clear antibiogram differences could be correlated with the presence or absence of integron structures, but sequence analysis of two of the internal integron regions indicated homology with genes encoding ANT(2'') adenyltransferase activity and AAC(6')-Ib acetyltransferase activity. Phenotypic analysis of aminoglycoside resistance profiles indicated that many isolates produced a combination of aminoglycoside-modifying enzymes, with most of the observed resistance to amikacin being associated with a gene encoding APH(3')-VI phosphotransferase, as detected by PCR. RAPD analysis indicated that all the Bilbao isolates producing APH(3')-VI were distinct from an epidemic integron carrying and APH(3')-VI-producing Acinetobacter strain found in other regions of Spain. It is concluded that, although class 1 integrons are widely disseminated amongst clinical isolates of A. baumannii from the Bilbao region of Spain, at present they are not playing a major role in the dissemination of antibiotic resistance genes in this region. PMID- 11192509 TI - Effect of fluconazole on agar invasion by Candida albicans. AB - Subinhibitory concentrations of azoles are known to inhibit hyphal branching of Candida albicans in liquid media. This study showed that subinhibitory concentrations of fluconazole also inhibit agar invasion by C. albicans in YPD solid medium. Agar invasion was markedly inhibited in two C. albicans strains that were resistant to fluconazole. This suggests that the degree to which fluconazole inhibits agar invasion by C. albicans hyphae could serve as a marker of susceptibility to azoles. PMID- 11192510 TI - Isolation and characterisation of an anticryptococcal protein in human cerebrospinal fluid. AB - An earlier study reported that human cerebrospinal fluid (CSF) has fungistatic activity for Cryptococcus neoformans. The present study reports that molecular sieve fractionation of concentrated CSF yielded three protein peaks, one of which (p2) had anticryptococcal activity. On a DEAE-Sephacel anion-exchange column the active molecular sieve peak (p2) gave two peaks that contained anticryptococcal activity. The first (DEAE-1) eluted with 0.1 M NaCl and the second (DEAE-2) eluted with 0.2 M NaCl in buffer. Fungistatic activity of DEAE-1 was reversed by FeCl3. Moreover, FeCl3 reversed inhibition of C. neoformans growth by CSF. In contrast, activity of DEAE-2 was not reversed by FeCl3, indicating that inhibition was produced by an iron-independent mechanism. Immunoblot assays showed that transferrin was present in DEAE-1 but not in DEAE-2, whereas albumin was present in DEAE-2 but not in DEAE-1. On NuPAGE, DEAE-1 protein migrated as a single band corresponding to transferrin and DEAE-2 protein gave a single band corresponding to albumin. In control experiments, human serum albumin subjected to the same isolation protocol acquired anticryptococcal activity similar to that of DEAE-2. Therefore, CSF albumin (DEAE-2) activity was associated with the isolation protocol. These data indicate that transferrin, present in or isolated from CSF, sequesters trace amounts of ferric iron, inhibits growth of C. neoformans and acts as an innate defence mechanism. PMID- 11192511 TI - Restriction endonuclease analysis of RAPD-PCR amplicons derived from Shiga-like toxin-producing Escherichia coli O157 isolates. AB - Shiga-like toxin-producing Escherichia coli O157 isolates were characterised by random amplification of polymorphic DNA by PCR (RAPD-PCR) analysis developed to allow robust epidemiological typing of E. coli. Amplification with primer 1247 or 1290 generated a reproducible profile, but was not capable of distinguishing sufficiently between epidemiologically unrelated strains. Subsequent digestion of the amplicons with selected restriction endonucleases improved the discriminatory ability of this method for strains showing limited differentiation following RAPD PCR analysis alone. Restriction endonuclease analysis of RAPD-PCR fragments generated from closely related strains has the potential to provide additional discriminatory information without loss of specificity. PMID- 11192512 TI - First isolation of Leptospira fainei serovar Hurstbridge from two human patients with Weil's syndrome. AB - Leptospira fainei serovar Hurstbridge is a recently discovered Leptospira species and so far it has only been cultured from animal sources. Based on positive serology and positive PCR for L. fainei among patients suspected of having leptospirosis, a role in human disease seems likely. This study describes two patients with Weil's disease from whom L. fainei was cultured. A local source of the infections was suspected, as these two patients resided in the same area of Denmark, were hospitalised approximately at the same time and had not been travelling recently. The Leptospira species was determined by serology, PCR and sequencing of bacterial DNA. One patient developed autoimmune hepatitis in the course of the L. fainei infection and was treated with both antibiotics and immunosuppression with good effect. The other patient had a self-limiting disease and did not receive any treatment. PMID- 11192513 TI - Effect of high-frequency oscillatory ventilation on the upper airways of kittens. AB - BACKGROUND: High-frequency oscillatory ventilation (HFOV) has become the preferred method of ventilation for the fragile lungs of neonates and infants because its beneficial effects on lungs are well known; however, its benefits on upper airways are not yet known. We investigated the effects of HFOV and conventional mechanical ventilation (CMV) on the airways of kittens with normal lungs. METHODS: Ten healthy cross-bred kittens, 2-3-months-old, with a mean bodyweight of 0.98 kg, were randomly divided into two groups: HFOV and CMV. Kittens were intubated and ventilated for 24 h. A semiquantitative scoring system was used to grade histopathological tissue changes in the cricoid, mid-trachea, carina and left bonchus. The injury scores of the two groups were ranked and compared using a two-tailed Mann-Whitney rank test. RESULTS: Histopathologic changes were similar and mild in both groups under light microscopic examination. There was no significant difference in airway injury between the two groups. CONCLUSIONS: We conclude that, in this animal model, HFOV results in minimal airway damage when properly managed and causes no greater tracheobronchial injury than CMV. PMID- 11192514 TI - Pulmonary sequelae in long-term survivors of bronchopulmonary dysplasia. AB - BACKGROUND: Bronchopulmonary dysplasia (BPD) is a common problem in premature babies. Long-term sequelae are the main concerns. METHODS: A retrospective review of all BPD children born in Queen Mary Hospital, a teaching hospital of the University of Hong Kong, from January 1987 to December 1995 was conducted. Children with cerebral palsy, immunodeficiency, congenital heart disorders, renal or liver failure were excluded from analysis. Chest radiography (CXR), electrocardiogram (ECG) and pulse oximetry were routinely performed. RESULTS: Fifty-five children completed the study. The female to male ratio was 1:1.1. The mean gestational age was 28 weeks. Twenty-five children were born with a birthweight of less than 1001 g. Mean age at assessment was 5.4 years. Twenty four children (44%) demonstrated signs or symptoms of current asthma. Only seven children managed to perform the spirometry satisfactorily. One child had low forced vital capacity and one had hyperresponsive airway. The only risk factor found to be associated with current asthma was the birth month, with those children born early in the year at higher risk of developing current asthma. Seventeen of 48 children (35%) had a bodyweight below the third percentile at the corrected age of 1 year. Eleven of these seventeen children (65%) demonstrated catch-up growth at assessment. Abnormal CXR was found in 25 of 40 children (63%). All had normal pulse oximetry and ECG. CONCLUSIONS: Bronchopulmonary dysplasia children had a significantly higher risk than the general population of developing current asthma (odds ratio 4.7; 95% confidence interval 3.4-6.5; P<0.0001). The importance of birth month suggests that early life experience is important in the pathogenesis of asthma, even in BPD children. The long-term growth of BPD children was much better than previously reported. PMID- 11192515 TI - Laparoscopic surgery in neonates and infants weighing less than 5 kg. AB - BACKGROUND: Laparoscopic surgery in small infants is still an uncommon procedure in Japan. The present study was conducted to evaluate the advantages and disadvantages of laparoscopic surgery in neonates and infants weighing less than 5 kg. METHODS: Between July 1997 and November 1999, 54 infants underwent laparoscopic surgery. They were evaluated for length of operation, intra- and postoperative complications, changes in intra-operative body temperature, time to postoperative feeding, length of hospital stay and changes in serum levels of C reactive protein (CRP), creatinine phosphokinase (CPK) and interleukin (IL)-6 on days 0, 1 and 4. These parameters in the laparoscopic pyloromyotomy (LP) and laparoscopic fundoplication groups were compared with those in the open pyloromyotomy (OP) and open fundoplication groups, respectively, which were performed during the same period. RESULTS: Three laparoscopy cases were converted to open procedures. One case of fundoplication had panperitonitis due to failed gastrostomy and required long-term parenteral nutrition. Time to postoperative feeding and length of hospital stay in the LP group were significantly shorter than in the OP group. In LP group, intra-operative body temperature did not markedly decrease during CO, pneumoperitoneum. Although serum levels of CRP, CPK and IL-6 were elevated in all groups on postoperative day 1, there were no significant differences between the groups. CONCLUSIONS: Better quality of life after laparoscopy is a significant advantage over conventional surgical procedures. This advantage not only outweighs the incidence of intra- and postoperative complications in small infants, but further emphasizes the need to improve laparoscopic techniques to avoid complications. PMID- 11192517 TI - Stepwise multimodal approach in the treatment of Kasabach-Merritt syndrome. AB - BACKGROUND: The purpose of the present study was to evalutate the various treatment modalities for Kasabach-Merritt syndrome (KMS) and to identify the most reliable treatment modalities. METHODS: A retrospective analysis was performed on 37 KMS patients who were admitted to Seoul National University Hospital between January 1979 and June 1999. Age, sex, locations of the hemangiomas, clinical symptoms and hematologic data were analyzed by multivariate logistical regression analysis to determine the response to various treatment modalities. RESULTS: Twenty-four of 37 patients (20 boys and 17 girls) were diagnosed during infancy. The locations of hemangioma were superficial skin in 31 patients, combined skin and visceral organs in four patients and visceral organs only in two patients. Tumor size was more than 5 cm in diameter in all cases, except for one. The treatment principle of KMS in our center involves a stepwise multimodal approach. Of the 37 cases, surgical resection was performed in two. Steroids were tried initially in 35 patients over a 1 week period, with an initial response rate of 11.4% (4/35). Combined steroid/radiation treatment was given in 28 cases, with a response rate of 75.0% (21/28). Four of five patients with additional interferon (IFN)-alpha therapy improved. No significant correlations were found between the prognostic factors, such as age, sex, size and locations of the hemangioma, hematologic data and the treatment modalities. CONCLUSIONS: Based on the experiences in a single center over a period of 20 years, we recommend a stepwise multimodal approach for the treatment of KMS; for example, steroid, radiation therapy and IFN-alpha in this order. However, surgical treatment is helpful if total resection is possible. PMID- 11192516 TI - Low serum lipids suggest severe bone marrow failure in children with aplastic anemia. AB - BACKGROUND: Significantly low serum lipid levels are occasionally seen at the time of diagnosis in children with aplastic anemia (AA). The aim of the present study was to clarify the pathologic and clinical significance of pretreatment serum lipid levels in AA. METHODS: A questionnaire seeking precise data about AA in pediatric patients, including the initial laboratory data at the time of onset of AA and the clinical course of these patients, was sent to 18 institutes in Japan; 13 institutes responded to the questionnaire. In this retrospective study, data concerning hematologic examination and serum lipids were available for analysis in 127 children with AA. Serum lipoprotein patterns were analyzed using conventional agarose electrophoresis in eight patients. In order to elucidate the cause of hypolipidemia in AA, we assayed serum macrophage colony stimulating factor (M-CSF), which is well known to have apparent cholesterol-lowering activity, by using an enzyme-linked immunosorbent assay in seven patients with hypocholesterolemia and compared the results with those obtained in patients with iron-deficiency anemia (IDA). RESULTS: We found that pretreatment total cholesterol (TC) and triglyceride levels in the serum correlated well with counts of both nucleated cells and hemopoietic cells in the bone marrow (BM) and were inversely correlated with the lymphocyte ratio in both the BM and peripheral blood. Patients with serum TC lower than 150 mg/dL showed a poor response to any form of therapy except BM transplantation. There was no difference in the serum lipoprotein patterns between the controls and patients examined. The serum M-CSF level was significantly higher in patients with TC levels lower than 150 mg/dL compared with controls. CONCLUSIONS: These results indicate that the pretreatment serum lipid level may reflect hematopoietic activity within the BM and can help to predict the therapeutic response of each case of AA to treatment with immunosuppressive drugs, corticosteroids and anabolic steroids. These results also indicate that M-CSF may be one of the contributing causes of the hypocholesterolemia that occurs in both AA and IDA. PMID- 11192518 TI - Short-term developmental outcome of iron prophylaxis in infants. AB - BACKGROUND: Previous studies on the cognitive effects of iron treatment have focused on anemic or non-anemic iron-deficient infants. The effect of iron supplementation on cognitive development among iron-sufficient infants has not been studied. The aim of the present study was to examine the effect of iron supplementation on performance in the Bayley Scales of Infant Development (BSID) and anthropometric measurement in 6-month-old iron-sufficient healthy infants. METHODS: Healthy, iron-sufficient infants who were 6 months of age and were attending the Well Baby Clinic were considered for enrollment. Infants were randomly assigned to take ferrous sulfate supplementation (1 mg/kg per day) or no supplementation and were followed for 3 months. Anthropometric measurement, hematologic status and BSID were evaluated on admission and after 3 months. RESULTS: Seven infants in the intervention group and nine in the control group completed the study. No significant differences were observed in anthropometric measurements and complete blood counts between the two groups after the 3 month study period. The mean transferrin saturation (TS) level decreased significantly in the control group during the study period (from 15.3+/-2.6 to 7.8+/-5.1%; P = 0.0117), but no such reduction was seen in the intervention group. At the end of the study, the TS of the control group was found to be significantly lower than that of the intervention group (7.8+/-5.1 vs. 19.9+/-7.9%, respectively; P = 0.0033). The BSID scores of infants in both groups were within the normal range on admission and at the end of the study period. CONCLUSIONS: Short-term iron supplementation did not change developmental test scores despite the hematologic response in iron-sufficient healthy infants. The high prevelance of iron deficiency anemia and its relationship with adverse developmental outcome suggests that prevention of iron-deficiency anemia with prophylaxis needs to be emphasized, rather than treatment. PMID- 11192519 TI - Killing of human Herpes virus 6-infected cells by lymphocytes cultured with interleukin-2 or -12. AB - BACKGROUND: Human Herpes virus 6 (HHV-6) is a causative agent of exanthema subitum and replicates mainly in lymphocytes. The aim of present study was to investigate cytotoxicity against HHV-6-infected cells by cord blood mononuclear cells (CBMC) and adult peripheral blood mononuclear cells (PBMC). METHODS: Human herpes virus 6-infected and -uninfected lymphocytes were used as target cells. Killing of target cells by CBMC and PBMC was investigated by the chromium release cytotoxicity assay. RESULTS: Freshly isolated CBMC and PBMC did not lyse HHV-6 infected and -uninfected cells. When CBMC and PBMC were cultured with interleukin (IL)-2, HHV-6-infected cells were significantly lysed compared with uninfected cells. Deletion of CD16+ cells by treatment of effector cells with anti-Leu-11b (CD16) antibody with complement reduced cytotoxicity against HHV-6-infected cells and T lymphocyte-rich cells did not lyse HHV-6-infected cells. Treatment of effector cells with anti-Fas ligand antibody and treatment of HHV-6-infected cells with anti-Fas antibody reduced cytotoxicity against HHV-6-infected cells. DNA fragmentation was detected in the supernatant from HHV-6-infected cells cultured with IL-2-activated lymphocytes. Culture of CBMC and PBMC with IL-12 also enhanced cytotoxicity against HHV-6-infected cells. CONCLUSIONS: These data suggest that lymphocytes cultured with IL-2 or IL-12 mediate killing against HHV 6-infected cells and killing of HHV-6-infected cells was through apoptosis. Fas Fas ligand interaction is one pathway by which HHV-6-infected cells are killed. Killing of HHV-6-infected cells by NK cells activated by cytokines may play a role in the recovery from HHV-6 infection in vitro. PMID- 11192520 TI - Plasma levels of granulocyte elastase-alpha1-proteinase inhibitor complex in children with hemolytic uremic syndrome caused by verotoxin-producing Escherichia coli. AB - BACKGROUND: Activated neutrophils play an important role in the pathogenesis of renal injury in humans and in experimental models of hemolytic uremic syndrome (HUS). To evaluate the clinical significance of the circulating granulocyte elastase-alpha1-proteinase inhibitor complex (GEPIC), which is a marker of neutrophil activation, we investigated the plasma concentrations of GEPIC in children with hemolytic uremic syndrome (HUS) associated with verotoxin-producing Escherichia coli (VTEC), VTEC gastroenteritis without HUS and in normal controls. METHODS: Of 22 children (1-19 years of age; mean age 5.5 years) with VTEC infection, nine were diagnosed with HUS. Plasma GEPIC, soluble thrombomodulin (sTM) and thrombin-antithrombin-III complex (TAT) levels were measured by ELISA. RESULTS: The number of polymorphonuclear leukocytes and the levels of plasma GEPIC in patients with HUS were significantly higher than those in non-HUS (9850+/-5091 vs. 5278+/-3327 /microL, P<0.05; 432.1+/-211.7 vs. 188.3+/-117.0 ng/mL, P<0.01) or control subjects (9850+/-5091 vs. 4728+/-1977 /microL, P<0.05; 432.1+/-211.7 vs. 105.9+/-51.1 ng/mL, P<0.001). Furthermore, plasma GEPIC levels showed a positive correlation with sTM (r = 0.522; P<0.01), a marker of endothelial cell injury, and TAT (r = 0.594; P<0.01), a marker of thrombin activity. CONCLUSIONS: These results suggest that an increase in circulating GEPIC levels in patients with VTEC-associated HUS may be related to endothelial injury, which may possibly lead to a more severe episode of this disease. PMID- 11192521 TI - Efficacy of interferon-alpha2b treatment in children with chronic hepatitis B who have previously undergone therapy for cancer. AB - BACKGROUND: The aim of the present study was to evaluate the efficacy of treatment with recombinant interferon (IFN)-alpha2b in 12 children with chronic hepatitis B who had previously undergone therapy for cancer. METHODS: Nine children had acute leukemias and the other three children had solid tumors. The mean (+/-SD) age of the children was 8.4+/-3.8 years (range 4-16 years). All cases were hepatitis B virus (HBV)-DNA positive and 11 were hepatitis B e antigen (HBeAg) positive. One was anti-HBe positive (mutant strain). Four cases were anti delta IgG positive. Liver biopsy revealed chronic hepatitis B in 11 patients and cirrhosis in one patient. Interferon-alpha2b was given at a dose of 5 MU/m2 three times a week, subcutaneously, for 12 months. RESULTS: Elimination of serum HBV DNA was obtained in three cases, but a further three patients demonstrated a marked decrease in HBV-DNA levels after therapy. Three of 11 patients seroconverted from HBeAg to anti-HBe. Alanine aminotransferase (ALT) levels returned to normal in three of nine cases in whom the ALT levels were high before treatment. At the end of therapy, the mean histologic activity index score was significantly diminished (P = 0.0039). CONCLUSIONS: In conclusion, a 12 month course of IFN-alpha2b induces some beneficial effects on virologic, biochemical and histologic indices in children with chronic hepatitis B who have previously undergone therapy for cancer. PMID- 11192522 TI - Transient hypogammaglobulinemia of infancy: clinical and immunologic features of 40 new cases. AB - BACKGROUND: Transient hypogammaglobulinemia of infancy (THI) results from a delay in the maturation of immunoglobulin production. METHODS: The clinical and immunologic data of 40 patients with THI are presented. Clinically, the majority of patients presented with recurrent respiratory infections and otitis media, bronchitis and/or bronchial asthma and recurrent gastroenteritis. RESULTS: Ten of 40 children had isolated low IgG; isolated low IgA and isolated low IgM were detected in one and three patients, respectively. At initial evaluation, levels of all three immunoglobluins were low in nine patients. Ten patients had diminished IgG and IgA levels, six had diminished IgA and IgM levels and one had low IgG and IgM levels. Two patients were given intravenous immunoglobulin replacement therapy for 1 year. None of the patients has experienced serious infections during their follow-up period. CONCLUSIONS: Prospective evaluation of patients (age range 5-60 months) revealed that immunoglobulin levels in 33 patients recovered before 36 months of age. Seven patients still had low immunoglobluin levels at 40-57 months of age. Three of these patients had low levels of both IgG and IgA, while two patients had low IgM levels and a further two patients had low IgA levels. PMID- 11192523 TI - Ventricular energetics in Fontan circulation: evaluation with a theoretical model. AB - BACKGROUND: Both pulmonary and systemic circulation must be maintained by a single pump in Fontan circulation. This unique property of Fontan circulation may be related to decreased exercise tolerance or increased instantaneous postoperative mortality rate, often observed in patients with this circulation. To better understand Fontan physiology, the present study theoretically investigated cardiac performance of Fontan circulation by using ventricular vascular coupling framework analysis. METHODS: End-systolic volume elastance (Ees), as a chamber contractile property, and effective arterial elastance (Ea), a lumped measure of ventricular afterload, were estimated both in normal left ventricular systemic circulation and in Fontan circulation. RESULTS: End-systolic volume elastance was decreased and Ea was increased in Fontan circulation. Both ventricular external stroke work (SW) and mechanical efficiency (EFF) under Fontan circulation were lower compared with those under normal circulation. Furthermore, the Ees-Ea relationship in Fontan circulation predicted limited cardiac reserve in terms of SW and EFF. Such cardiac performance in Fontan circulation stemmed from increased impedance due to the additional connection of the pulmonary vascular bed to the systemic vasculature and from the lack of a compensatory increase in contractility for increased afterload. CONCLUSIONS: Thus, it was inferred that Fontan circulation had intrinsic disadvantages and this may explain, in part, abnormal functional status and decline in survival following this procedure. PMID- 11192524 TI - Restenosis after balloon angioplasty of coarctation: relationship with ductus arteriosus. AB - BACKGROUND: Recently, balloon angioplasty (BA) has been used for the treatment of coarctation of the aorta (CoA) and the effectiveness of this treatment has been reported. However, the restenosis rate following BA in native CoA in the infant is high and the cause may be related to tissue properties at the origin of the ductus arteriosus (DA). However, the mechanisms responsible for restenosis remain uncertain. METHODS/RESULTS: The present study was designed to examine transformation of the smooth muscle cell (SMC) phenotypes using immunohistologic studies and to investigate the cause of restenosis of CoA following BA. A CoA model was surgically created in 15 newborn pigs (10-14-days-old; 2.4-4.1 kg). Balloon angioplasty was performed 1 month after the initial operation. One or 3 months after BA, animals were killed and immunohistologic studies on smooth muscle cell (SMC) antibodies against SM1, SM2 and SMemb of the myosin heavy chain (MHC) isoform were performed in the aorta at the CoA and DA. In the neointima, only SMemb was positive. In the SMC layer of the DA, only SM2 was positive. One month after BA, the external layer of the tunica media was strongly positive for SM2 only in the area around the origin of the DA. CONCLUSIONS: The first cause of restenosis is obstructive neointimal formation caused by the proliferation of undifferentiated SMC into the subendothelial tissue. This proliferation seems to be triggered by BA. The distribution of SM2 1 month after balloon angioplasty showed a similar pattern of proliferation of SMC in the external layer around the DA. This may represent a second mechanism of restenosis. PMID- 11192525 TI - Headache etiology in children: a retrospective study of 125 cases. AB - BACKGROUND: To determine the headache etiology in children in the middle Anatolia region of Turkey. METHODS: The clinical and laboratory findings of 125 patients, who were followed up after a diagnosis of headache in our hospital, were reviewed retrospectively. The criteria defined by the International Headache Society (IHS) were used in the classification of patients. The patients were divided into two subgroups according to age intervals: (i) group 1, 5-10 years of age; and (ii) group II, 11-16 years of age. RESULTS: There were 62 males and 63 females in the study. The patients' ages ranged from 5 to 16 years (mean (+/- SD) age 10.67+/ 2.72 years). Headache was more commonly noted between 11 and 16 years of age. While headache was more frequent in male children in group I, there was female predominance in group II. However, there was no significant difference between the groups with respect to age and gender (P>0.05). The most frequent cause of headache was migraine and the remaining causes, in decreasing order, included sinusitis (no. 11 according to IHS criteria) and tension-type and psychosomatic headaches (no. 13 according to IHS criteria). Of the 125 patients in the study, 85 (68%) had acute headache and 40 (32%) had chronic headache; 44 (35.2%) patients had acute localized-type headache, 39 (31.2%) suffered from acute recurrent-type headache, 38 (30.4%) had chronic non-progressive headache and acute generalized and chronic progressive-type headache were diagnosed in two (1.6%) patients. Computed tomography (CT) and magnetic resonance imaging (MRI) of the brain were performed in 50 and seven patients, respectively; there were abnormal findings in six patients on CT examiniation and in two patients following MRI. CONCLUSIONS: In conclusion, we stress that the most frequent cause of headache in childhood is migraine and the remaining causes, in decreasing order of frequency, were sinusitis and tension-type and psychosomatic headaches. Neuroimaging studies, such as CT or MRI, need to be performed, especially in patients with complicated symptoms. PMID- 11192526 TI - Safety and immunogenicity of live attenuated varicella vaccine in 9-month-old children. AB - BACKGROUND: The present study was conducted to evaluate the safety and immunogenicity of live attenuated varicella vaccine (Oka-strain) in 9-month-old infants. METHODS: One hundred and fourteen infants were vaccinated once with live attenuated varicella vaccine (Valrix; SmithKline Beecham Biologicals, Rixensart, Belgium) containing a mean virus titer of 10(4.0) plaque-forming units (p.f.u.) per dose. Signs and/or symptoms after vaccination were followed for 42 days. Home visits were made to detect solicited local reactions (0-3 days) and solicited general reactions (0-21 days), as well as unsolicited reactions. Specific varicella antibodies were determined by an indirect immunofluorescence method. The geometric mean titer and seroconversion rate were calculated. RESULTS: Signs and/or symptoms were reported in 47.4% (54/114) of cases following vaccination. The only local symptom reported was pain on digital pressure at the injection site and this was reported in 28.1% (32/114) of infants. General symptoms were reported in 38.6% (44/114) of cases. The most frequently reported findings were fever (27.2%), which was mostly mild, restlessness (20.2%) and cough (11.4%). Only four unsolicited symptoms were reported and they were all unrelated to vaccination. No serious adverse event was reported. Of the 109 infants included in the immunogenicity analysis, 105 were seronegative and four were seropositive for antibodies against varicella before vaccination. The vaccine elicited seroconversion in 97.1% of initially seronegative cases. The post-vaccination geometric mean titer for these infants was 30.9 geometric mean titer (GMT). CONCLUSIONS: The vaccine was found to be safe and immunogenic when given to infants as young as 9 months of age. This may be of clinical significance during outbreaks of varicella and especially for developing countries. PMID- 11192527 TI - Pattern of human leukocyte antigens in Turkish children with celiac disease. AB - BACKGROUND: Regional variations in the human leukocyte antigen (HLA) distribution patterns of celiac disease (CD) have been reported. The aim of the present study was to assess the distribution of HLA class I and class II in Turkish children with CD and to compare the findings with a control group. METHODS: Human leukocyte antigen typing was performed in 33 children with CD and in 77 healthy individuals, who served as controls, by using standard National Institutes of Health lymphocytotoxicity techniques. RESULTS: A positive association was found between HLA A2 (42 vs 19% for sick subjects compared with healthy controls, respectively), B8 (39 vs. 9% for sick subjects compared with healthy controls, respectively), CW7 (45 vs. 25% for sick subjects compared with healthy controls, respectively), DR3 (70 vs. 17% for sick subjects compared with healthy controls, respectively), DR7 (30 vs. 13% for sick subjects compared with healthy controls, respectively) and DQ2 (52 vs. 34% for sick subjects compared with healthy controls, respectively). The combinations of DR3-DQ2 (30 vs. 12% for sick subjects compared with healthy controls, respectively), DR3-DR4 (21 vs. 1% for sick subjects compared with healthy controls, respectively) and DR7-DQ2 (21 vs. 6% for sick subjects compared with healthy controls, respectively) were also found to be significantly important in children with CD. The highest relative risk (RR) was for HLA B8 in class I (RR 6.50), for DR3 (RR 11.30) in class II and for combination of DR3-DR4 (RR 20.46). The highest etiologic fraction (EF) was for the DR3 antigen (EF 0.55). CONCLUSIONS: The present study emphasizes that HLA genotypes are an important background to CD development, but some additional susceptibility factors remain to be identified. PMID- 11192528 TI - Can zinc deficiency be used as a marker for the diagnosis of celiac disease in Turkish children with short stature? AB - BACKGROUND: It is generally accepted that celiac disease (CD) must always be considered when dealing with growth failure in children. Therefore, it is important to develop screening tests for detecting patients that need an intestinal biopsy. The aim of the present study was to investigate the value of plasma zinc levels for the diagnosis of monosymptomatic CD in short-statured children. METHODS: Fourty-nine children with a short stature and 34 healthy controls were investigated. Plasma zinc levels were assayed by atomic absorption spectrophotometry in short-statured children and controls. All patients with short stature underwent endoscopic small intestinal biopsy. RESULTS: Duodenal mucosal histopathology was normal in 25 children. Low plasma zinc values were observed in 54.2% of patients with CD, 32.0% of patients with idiopathic short stature and 14.8% of controls. The mean values of plasma zinc levels were not significantly different among the three groups. Sensitivity, specificity and the positive and negative predictive values for plasma zinc were 45.8, 76.0, 64.7 and 59.4%, respectively. CONCLUSIONS: These results indicate that zinc deficiency is an important problem in CD children with short stature; however, plasma zinc levels are not useful as a screening test for selecting patients for jejunal biopsy. PMID- 11192529 TI - 3beta-hydroxy-delta5-C27-steroid dehydrogenase/isomerase deficiency in a 23-year old woman. PMID- 11192530 TI - Point mutation in intron 11 of Bruton's tyrosine kinase in atypical X-linked agammaglobulinemia. PMID- 11192531 TI - Hemorrhagic telangiectasia with thrombocytopenia in a newborn infant. PMID- 11192532 TI - Neonatal listeriosis with severe respiratory failure responding to nitric oxide inhalation. PMID- 11192533 TI - Liver abscess due to Lactococcus lactis cremoris. PMID- 11192534 TI - A case of persistent Enterobacter cloacae bacteremia. PMID- 11192535 TI - Possible splenic tuberculosis presenting as unexplained fever. PMID- 11192536 TI - Childhood idiopathic thrombocytopenic purpura associated with human parvovirus B19 infection. PMID- 11192537 TI - Coxiella burnetii lymphadenitis: a possible fever focus in acute Q fever. PMID- 11192538 TI - Intrathoracic kidney combined with pneumomediastinum in an asphyxiated neonate. PMID- 11192539 TI - N-acetyl-L-cysteine inhibits bleomycin-induced interleukin-8 secretion by bronchial epithelial cells. AB - OBJECTIVE: Bleomycin (BLM) has proven effective for the treatment of cancers, but the most serious dose-limiting side-effect is the development of pulmonary toxicity. Although the precise mechanism in the pathogenesis of BLM-induced lung injury has not been determined, oxygen radicals and neutrophils are indicated to play a key role in it. Interleukin-8 (IL-8) is thought to be an important mediator of the pathogenesis of acute lung injury. METHODOLOGY: The IL-8 production from bronchial epithelial cell line, BEAS-2B cells was measured by enzyme-linked immunosorbent assays for IL-8. RESULTS: The concentrations of IL-8 were reportedly elevated in BLM-induced lung injury, suggesting the involvement of IL-8 in the pathogenesis of BLM-induced lung injury. In the present study, we showed that BLM induced the expression of IL-8 protein and mRNA in BEAS-2B cells, and N-acetyl-L-cysteine (NAC) inhibited IL-8 expression. In addition, the structurally unrelated antioxidant, pyrrolidine dithiocarbamate (PDTC) also effectively inhibited BLM-induced IL-8 production. CONCLUSION: These results suggest that anti-oxidant-sensitive mechanism might be involved in the inhibition of IL-8 secretion by BLM-stimulated bronchial epithelial cells and that NAC might be useful for the treatment of BLM-induced lung injury. PMID- 11192540 TI - Increased incidence of autoantibodies to interleukin-1a in rheumatoid arthritis with interstitial lung disease. AB - OBJECTIVE: To clarify the clinical significance of autoantibodies (auto-Ab) to interleukin-1alpha (IL-1alpha) in rheumatoid arthritis (RA) with interstitial lung disease (ILD), we examined the IL-1alpha auto-Ab level in serum of patients with RA with/without ILD. METHODOLOGY: We investigated the level of IL-1alpha auto-Ab in serum of 70 patients with RA with/without ILD and 40 control patients (CP). Levels of IL-1alpha auto-Ab were measured by radioimmunoassay, and serum was regarded as IL-1alpha auto-Ab positive at an auto-Ab level of more than 5 ng/mL. RESULTS: Interleukin-1alpha auto-Ab was detected in the serum of 30 out of 70 RA patients (42.9%), and six out of 40 CP (15%) (P < 0.05). Interleukin-1alpha auto-Ab were detected in the serum of 18 out of 32 patients with RA with ILD (56.2%) and 12 out of 38 patients with RA without ILD (31.5%). The positive rate of these autoantibodies in RA with ILD was significantly higher than that in RA without ILD (P < 0.05). Although C-reactive protein, immunoglobulin G, rheumatoid factor and rheumatoid arthritis particle agglutination levels in serum from patients with RA with ILD were not significantly different between the IL-1alpha auto-Ab-positive and -negative groups, the lactate dehydrogenase level (LDH) and AaDO, in the IL-1alpha auto-Ab-positive group were significantly higher than those in the negative group (LDH: P < 0.001, AaDO2: P < 0.05). CONCLUSION: These results suggest that IL-1alpha auto-Ab are generated in response to the immunoinflammatory process of ILD in RA, and these autoantibodies may neutralize and regulate the IL-1alpha activity. PMID- 11192541 TI - Determination of adenosine deaminase activity and its isoenzymes for diagnosis of pleural effusions. AB - OBJECTIVE: We aimed to investigate adenosine deaminase (ADA) activity and the activities of its ADA1 and ADA2 isoenzymes in pleural effusions and also sera with different aetiological origins. METHODOLOGY: The pleural effusions of 87 patients were examined. The patients were separated into four groups: transudates, parapneumonic, malignant, and tuberculous effusions. The cases were also designated as tuberculous or non-tuberculous group. Adenosine deaminase activity was determined by the colorimetric method described by Giusti and Galanti. RESULTS: The intermean differences were statistically significant for total ADA, ADA1 and ADA2, except for pleural fluid ADA1 in the malignant group when compared to the tuberculous effusion group. The intermean differences between the tuberculous and non-tuberculous group were statistically significant for all three parameters except for pleural fluid and serum ADA1 activity. The sensitivities of total ADA, ADA1 and ADA2 activities for tuberculosis were 91, 57 and 93%, respectively; their specificities 89, 88 and 92%, respectively; their positive predictive values 82, 70 and 86%; and their diagnostic accuracies 89, 76 and 92%, respectively, in pleural fluid. CONCLUSIONS: Determination of ADA and its isoenzymes can help to differentiate the causes of pleural effusion. Increased ADA2 activity is a striking marker of tuberculous effusions. In contrast, increased ADA1 activity was significantly elevated in parapneumonic effusions. PMID- 11192542 TI - The role of cytokine-induced neutrophil chemoattractant-1 in neutrophil-mediated remote lung injury after intestinal ischaemia/reperfusion in rats. AB - OBJECTIVE: Remote lung injury is induced by ischaemia/reperfusion (I/R) of the gastrointestinal tract and the liver following hypovolaemic shock. In the present study, the role of cytokine-induced neutrophil chemoattractant (CINC), a member of the interleukin (IL)-8 family, in neutrophil-mediated remote lung injury following intestinal I/R was investigated in anaesthetized rats. METHODOLOGY: The I/R group was subjected to 60 min of occlusion of the superior mesenteric artery with laparotomy, followed by 240 min of intestinal reperfusion. The sham-operated (sham) group was subjected to the same procedures with the exception of intestinal I/R. RESULTS: In the I/R group, the permeability index of the lung, the neutrophil count in pulmonary vascular lavage fluid and bronchoalveolar lavage fluid (BALF), lung myeloperoxidase activity and neutrophil oxidative production were all significantly greater than those in the sham group. Cytokine induced neutrophil chemoattractant-1 levels in blood and BALF were significantly increased at 240 min after intestinal reperfusion. There was a significant relationship between neutrophils in BALF and CINC-1 level in BALE CONCLUSION: These findings suggest that intestinal reperfusion was associated with activation and accumulation of neutrophils in the lung and resulted in remote lung injury with increased microvascular permeability. Thus, CINC-1 in BALF may induce neutrophil migration from the pulmonary vessels to the interstitium and alveolar spaces in remote lung injury after intestinal I/R. PMID- 11192543 TI - Echocardiographic findings of pericardial involvement in patients with malignant pleural mesothelioma with a history of environmental exposure to asbestos and erionite. AB - OBJECTIVE: The aim of the present study was to evaluate the pericardial involvement in patients with malignant mesothelioma caused by exposure to different minerals. METHODOLOGY: Forty-two patients (mean age of 52 +/- 12 years) with malignant mesothelioma were examined with transthoracic echocardiography. Thirty-three (78.9%) patients had a history of environmental exposure to asbestos and nine (21.4%) had a history of environmental exposure to erionite. RESULTS: In 19 (45.2%) patients with malignant pericardial mesothelioma, pericardial involvement was determined by echocardiography. The other 23 (54.8%) patients had no pericardial involvement. Pericardial effusion was detected in nine (64.3%) patients and pericardial effusion was small in six (14.3%) patients, moderate in one (2.4%) patient and large in two patients. Thickening of the pericardium was observed in eight (19%) patients. In another two (7.1%) patients pericardial calcification was observed. Among the 33 patients who had been exposed to asbestos, 15 (45.5%) had pericardial involvement, and among the nine patients with a history of exposure to erionite, four (44.4%) had pericardial involvement. There was no difference in terms of pericardial involvement in different stages of the tumour (P > 0.05). CONCLUSIONS: Pericardial involvement is commonly seen in patients with malignant mesothelioma. Among patients exposed to asbestos or zeolite there was no difference in terms of pericardial involvement. Furthermore, pericardial involvement was not related with the stage of the tumour. PMID- 11192544 TI - Comparison between tidal breathing and dosimeter methods in assessing cough receptor sensitivity to capsaicin. AB - OBJECTIVE: Dosimeter method and tidal breathing method have been used to assess cough sensitivity to inhaled capsaicin, a C-fibre ending stimulator. The aim of the present study was to evaluate the repeatability of and the agreement between the two methods. METHODOLOGY: Cough threshold, the lowest concentration of capsaicin causing five or more coughs, was measured twice 1-3 weeks apart by each method in 26 normal subjects. Increasing concentrations of capsaicin were inhaled by a single breath in the dosimeter method or by 15 s tidal breathing in the tidal breathing method in 1 min intervals. RESULTS: Coefficients of repeatability of the cough threshold measurement were 1.89 and 2.71 doubling concentration in the tidal breathing method and the dosimeter method, respectively, suggesting good repeatability in the cough threshold measurement by both methods. The cough threshold was significantly (P < 0.0001) greater by 1.75 doubling concentration on the dosimeter method than the tidal breathing method. The coefficient of agreement between the two methods was 2.53 doubling concentration. Five subjects complained of burning sensation in the throat in the dosimeter method but no patient complained about the tidal breathing method (P < 0.05). CONCLUSIONS: Although the agreement between the two methods was considered to be good, higher concentrations of capsaicin solution were required to determine the cough threshold in the dosimeter method, resulting in an unpleasant sensation in the throat. PMID- 11192545 TI - Parasympathetic neurotransmission in rabbit isolated bronchus is modulated at prejunctional sites via endothelinB receptor stimulation. AB - OBJECTIVE: The aim of this study was to investigate the mechanism involved in endothelin-induced potentiation of the response to parasympathetic nerve stimulation. METHODOLOGY: We used autoradiographic and functional studies in rabbit isolated bronchi. RESULTS: Autoradiography revealed dense binding sites for radiolabelled endothelin-3 over bronchial parasympathetic ganglia. The contractile response of the bronchus to electrical field stimulation was significantly potentiated by endothelin-3, endothelin-1, sarafotoxin S6c and BQ 3020 to 326+/-53%, 293+/-63%, 514+/-119% and 655+/-178%, respectively, of control values. The endothelin-3-induced potentiation of neurally evoked responses was not affected by the presence of propranolol, phentolamine or hexamethonium. The potentiation was also unaltered by pretreatment with the endothelinA receptor antagonist BQ-123 (3 micromol/L), but was significantly reduced in the presence of the combined endothelinA/endothelinB receptor antagonist PD 145065, indicating that the potentiation was mediated via endothelinB receptors. Confirmation of endothelinB receptor involvement in the neuropotentiation was obtained by demonstration of a significant amelioration of the potentiation in the presence of the endothelinB receptor selective antagonist BQ-788, and after endothelinB receptor desensitization by the endothelin, receptor selective agonist sarafotoxin S6b. CONCLUSIONS: These results suggest that the endothelin-induced potentiation of parasympathetic neural responses in the rabbit bronchus is mediated via endothelinB receptor activation. PMID- 11192546 TI - Lung cancer in patients younger than 40 years in a multiracial Asian country. AB - OBJECTIVE: This study aimed to determine whether the clinicopathological features of lung cancer in patients younger than 40 years differ from that of older patients in an Asian country. METHODOLOGY: We undertook a review of the clinicopathological data of all patients with confirmed primary lung cancer at the Department of Medicine, University of Malaya Medical Centre, Kuala Lumpur, Malaysia, from October 1991 to September 1999. RESULTS: Of the 580 patients with lung cancer, 36 (6.2%; 23 males, 13 females) were 21-39 years old at diagnosis. The percentage of people who had never smoked was higher among the younger patients (58.3% vs 19.1%, P < 0.001). Although adenocarcinoma was the most common cell type in both groups, its incidence was higher in the younger patients (24/36 (66.7%) vs 228/544 (41.9%), P = 0.007). The mean World Health Organization performance status at presentation was worse in the younger patients (2.4 vs 2, P = 0.007). In the case of non-small cell lung cancer, all the younger patients presented with either stage IIIb or metastatic disease compared to 77.2% of the older patients (P < 0.001). CONCLUSIONS: Younger lung cancer patients were more likely than older patients to have never smoked, to have adenocarcinoma, and to present with poorer performance status and with more advanced-stage non-small cell lung cancer. PMID- 11192547 TI - A comparative analysis of the biochemical parameters used to distinguish between pleural exudates and transudates. AB - OBJECTIVE: The aim of the present study was to compare the various parameters used to identify exudates. METHODOLOGY: The study included 255 patients with pleural effusions. According to aetiological diagnosis, 105 pleural effusions were labelled as transudates and 150 were labelled as exudates. RESULTS: Using the criteria of Light et al., 94.5% of the effusions were correctly classified, yielding a sensitivity and specificity of 99.3% and 87.6%, respectively. Use of the pleural fluid/serum bilirubin ratio produced results of 92.9%, 90.7%, and 96.2%, respectively. Using pleural fluid cholesterol level yielded results of 95.7%, 95.3%, and 96.2%, respectively. When the combination of pleural fluid cholesterol level and lactate dehydrogenase (LDH) level was used, the specificity and accuracy were found to be higher than that using the criteria of Light et al. We found that there was no significant difference among the parameters with respect to accuracy. CONCLUSION: When the accuracy and cost are considered, differentiation of pleural exudates and transudates can be achieved only by pleural fluid cholesterol level or LDH level; and when two parameters were used together, the accuracy and specificity were higher than that using the criteria of Light et al. PMID- 11192548 TI - Bronchiolitis obliterans in children: clinical profile and diagnosis. AB - OBJECTIVE: The aim of the study was to determine the clinical profile, aetiology and radiological categories in children diagnosed with bronchiolitis obliterans (BO). METHODOLOGY: We undertook a review of the medical records and radiological studies of 14 children with BO. RESULTS: Unresolving cough and wheeze after a short respiratory illness was the commonest presentation. A viral pneumonitis was identified as the initial respiratory event prior to the development of BO in six children and Mycoplasma pneumoniae was the cause in another three children. Chest X-ray findings could be divided into four distinct patterns that were hyperinflation (n=5), mixed pattern of atelectasis, hyperlucency and bronchial thickening (n=4), unilateral small hyperlucent lung (n=3) and unilateral collapse of one lung (n=2). High resolution computed tomogram (HRCT) chest showing areas of hyperaeration and mosaic ground glass patterns with bronchial thickening were commonly found in patients whose chest X-ray showed bilateral changes. Patients with bilateral lung changes were more likely to have failure to thrive and persistent respiratory symptoms on follow up. CONCLUSION: A diagnosis of BO can be made from typical clinical features combined with an understanding of the different chest X-ray categories and HRCT of the chest. A viral aetiology was the commonest cause for BO in our series. PMID- 11192549 TI - Tracheobronchopathia osteochondroplastica. AB - Tracheobronchopathia osteochondroplastica (TO) is a rare disorder with unknown aetiology. We report one case of TO in a patient with non-Hodgkin pulmonary lymphoma and benign epidermal and trichylemmal cysts on the periorbital region and scalp. To the authors' knowledge, the coincidence of these processes has never been described before. The case was evaluated with conventional X-ray, computed tomography, magnetic resonance imaging, fibre-optic bronchoscopy with 2 months interval, histopathological evaluation, Tc-99 m MDP bone scintigraphy and microbiological studies including PCR testing of bronchial biopsy and lavage specimens for Mycobacterium tuberculosis. Additionally, case reports of TO in the Turkish literature are summarized. PMID- 11192551 TI - Respiratory bronchiolitis associated interstitial lung disease (RB-ILD) presenting with haemoptysis. AB - Respiratory bronchiolitis associated interstitial lung disease is an uncommon condition in current or ex-smokers. The presentation is non-specific, but haemoptysis is uncommonly reported in this condition. We report the case of a 25 year-old woman who presented with significant haemoptysis, dyspnoea, reduced transfer factor and normal clinical examination. In addition, a Medline literature search was performed to review the clinical features and prognosis of this disease. Other causes of haemoptysis were excluded with extensive investigation. The diagnosis was made on thoracoscopic lung biopsy. The patient had significant postoperative complications of prolonged air leak and hydropneumothorax requiring further surgery and prolonged hospital stay. Advice regarding smoking cessation was given. Her pulmonary physiology remains abnormal on follow up but symptoms have improved. Respiratory bronchiolitis-ILD may present with normal examination and radiology. Haemoptysis in this case may have been associated with the underlying disease but could have been incidental. Diagnosis, in general, requires lung biopsy. As in this patient, lung function does not appear to improve significantly on follow up. PMID- 11192550 TI - A case of pulmonary arteritis with stenosis of the main pulmonary arteries with positive myeloperoxidase-antineutrophil cytoplasmic autoantibodies. AB - A 53-year-old woman was referred to our hospital with the main symptoms of productive cough, fever and exertional dyspnoea. Chest X-ray revealed enlargement of the left hilar shadow and cavitary infiltration in the right upper lobe. 99mTechnetium-macroaggregated albumin (99mTc-MAA) perfusion scintigram showed complete hypoperfusion through the entire right lung. A pulmonary angiogram revealed stenotic lesions in the right and left main pulmonary arteries. Right cardiac catheterization showed an elevated right ventricular systolic pressure. There was no evidence of systemic arterial lesions nor vasculitis. The patient was positive for myeloperoxidase (MPO)-antineutrophil cytoplasmic autoantibodies (ANCA) (168 EU). The Mycobacterium avium complex sputum culture was positive. The pulmonary stenotic lesions were surgically resected. The resected pulmonary arterial lesions were pathologically diagnosed as non-specific vasculitis. The cavitary lesion disappeared 6 months after the surgery. Two years after the surgery, although the MPO-ANCA level had decreased to 12 EU, stenosis of the pulmonary arteries reappeared. It is suggested that the patient became positive for MPO-ANCA in association with the Mycobacterium avium complex infection, and that the presence of MPO-ANCA may not be related to the development of pulmonary stenosis of the main pulmonary arteries. PMID- 11192552 TI - Use of montelukast in the treatment of early childhood wheezing from clinical experience with three cases. AB - Leukotrienes were found to be raised in respiratory syncytial virus bronchiolitis. Montelukast is a cysteinyl leukotrienes antagonist. We report our experience with the use of montelukast in three young children from 5-months to 20-months old. The first case was a 5-month-old boy with previous good health. He had prolonged respiratory distress secondary to adenovirus type 3 infection. The second case was a 20-month-old boy with bronchopulmonary dysplasia. He had respiratory syncytial virus and an adenovirus type 3 infection leading to prolonged wheeze. The third case was a 20-month-old girl with chronic lung disorder after an episode of severe E. coli pneumonia at 1 month old. She developed acute virus-negative severe wheeze after a few days of running nose and low-grade fever. All three cases responded poorly to inhaled steroids and bronchodilators. Addition of montelukast was associated with marked clinical improvement within 1 week. The three cases were very heterogeneous and differed from usual simple virus-induced acute bronchiolitis. The use of multiple drugs including montelukast did not enable any definite conclusions; however, the addition of montelukast was closely related to clinical improvement. Further studies in the use of montelukast in severe virus-induced bronchiolitis are warranted. PMID- 11192553 TI - Pulmonary nocardiosis during immunosuppressive therapy for idiopathic pulmonary fibrosis. AB - Nocardiosis is a subacute or chronic suppurative infection caused by Nocardia species. Although it is more common in immunocompromised hosts, idiopathic pulmonary fibrosis (IPF) has not been recognized as a predisposing factor for nocardial infection. We report a case of IPF, in which pulmonary nocardiosis developed during treatment with prednisolone and cyclophosphamide. The risk of pulmonary nocardiosis may be increased in cases of IPF on immunosuppressive therapy. Since IPF often accompanies lung carcinoma, it is important to correctly differentiate nocardiosis from carcinoma. PMID- 11192554 TI - An unusual case of double tuberculous broncho-oesophageal fistulas in an adult. AB - Broncho-oesophageal fistula associated with tuberculosis is rarely reported in the literature and has not been reported in Hong Kong. We describe a 30-year-old Chinese human immunodeficiency virus (HIV)-negative man with double tuberculous broncho-oesophageal fistulas proven by histology. Constitutional symptoms of active tuberculosis were absent and chest radiograph did not show an obvious lung lesion. Our case shows that broncho-oesophageal fistula can be the sole manifestation of active tuberculosis and that the diagnosis should be suspected in patients who are seen with chronic respiratory symptoms in areas where the prevalence of tuberculosis is high. PMID- 11192555 TI - The rapid diagnosis of smear-negative pulmonary tuberculosis: a cost effectiveness analysis. AB - OBJECTIVE: The prompt diagnosis of smear-negative pulmonary tuberculosis (PTB) is a clinical challenge. It may be achieved by a number of tests which have varying accuracies, costs and degrees of invasiveness. The objective of this study was to compare the cost-effectiveness of clinical judgement (empirical), the Roche Cobas amplicor assay for Mycobacterium tuberculosis (amplicor), acid-fast staining of bronchoalveolar lavage specimens (BAL), nucleic acid amplification tests of bronchoalveloar lavage specimens for M. tuberculosis (BAL + NAA), computed tomography (CT) and amplicor assay followed by BAL. METHODOLOGY: The range of predictive values of the various strategies were derived from published data and a new study of 441 consecutive adult patients with suspected smear-negative PTB prospectively stratified into three pretest risk groups: low, intermediate and high. The cost-effectiveness was evaluated with a decision tree model (DATA software). RESULTS: The incidence of PTB was 5.7% (4% culture positive) for the whole group, 95% in the high-risk group, 0.9% in the low-risk group and 3.4% in the intermediate-risk group. The sensitivity of the empirical approach was 49% and of the amplicor assay was 44%. Patient outcomes were expressed as life expectancy for the base case of a 58-year-old man with a pretest probability of 5.7%. At this low pretest risk the differences in life expectancies between tests was < 0.1 years and the empirical approach incurred the lowest cost. Sensitivity analysis at increasing pretest risks showed better life expectancies (approximately 1 years) for CT scan and test combinations than empirical and amplicor for additional costs of US$243-US$309. Bronchoalveolar lavage had the worst overall cost-effectiveness. CONCLUSIONS: We conclude that the pretest risk of active PTB was a key determinant of test utility; that the AMPLICOR assay was comparable to clinical judgement; that BAL was the least useful test; and that with increasing risks, CT scan and test combinations performed better. Further studies are needed to better define patients with intermediate risk for PTB and to directly compare the cost-effectiveness of more sensitive nucleic acid amplification tests such as the enhanced Gen Probe, CT scan and test combinations/sequences in these patients. PMID- 11192556 TI - Bronchoscopic, radiologic and pulmonary function evaluation of endobronchial tuberculosis. AB - OBJECTIVE: Endobronchial tuberculosis (EBTB) causes problems in both making a diagnosis and following up the endobronchial lesion, because the lesion is not evident in simple chest radiograph. Frequently, the diagnosis and follow up of EBTB lesion during treatment mainly depend on bronchoscopy. Chest computed tomography (CT) and pulmonary function test (PFT) have also been used in evaluating EBTB and differentiating it from the other diseases. Primary purpose of the present study was to observe the change of EBTB lesion during treatment and determine the optimal time and the indication of follow-up bronchoscopy. We also evaluate the usefulness of chest CT and PFT in EBTB. METHODOLOGY: Eighty-one biopsy-proven EBTB patients were enrolled from 1992 to 1997. Endobronchial tuberculosis was classified into seven subtypes: actively caseating, fibrostenotic, oedematous-hyperaemic, tumorous, ulcerative, granular, and non specific bronchitic type according to bronchoscopic features by Chung's Classification. The change of bronchoscopic findings during treatment in each subtype of EBTB was evaluated prospectively. Follow-up bronchoscopy was done each month until there was no subsequent change in endobronchiat lesion, and every 3 months thereafter, and at the end of treatment. Chest CT and PFT were performed in 26 and 68 patients respectively, at initial bronchoscopy. RESULTS: Twenty-two of the 34 cases of actively caseating EBTB changed into the fibrostenotic type, and the other 12 healed without sequelae. Seven of the 11 cases of oedematous hyperaemic EBTB changed into the fibrostenotic type, and the other four healed. Nine of the 11 cases of granular EBTB, six cases of non-specific bronchitic EBTB, and two cases of ulcerative EBTB resolved completely. However, the other two cases of granular EBTB changed into the fibrostenotic type. Seven cases of fibrostenotic EBTB did not improve despite antituberculosis chemotherapy. These various changes in bronchoscopic findings occurred within 3 months of treatment. In 10 cases of tumorous EBTB, seven progressed to the fibrostenotic type. In addition, new lesions appeared in two cases, and the size of the initial lesions increased in another two cases, even at 6 months after treatment. On chest CT findings of 26 EBTB patients, the length of bronchial involvement was measured from 10 to 55 mm. Bronchial stricture was noticed in 25 cases and the range of narrowing was from total occlusion to near normal, and there was wide variation in bronchial stricture even within same subtype of EBTB. The dominant feature of PFT in EBTB at the diagnosis was restrictive pattern. CONCLUSION: The therapeutic outcome of each subtype of EBTB can be predicted by follow-up bronchoscopy during the initial 3 months, with the exception of the tumorous type. In tumorous EBTB, the evolution of the lesions during treatment is very complicated, and bronchial stenosis may develop at a later time. Chest CT was useful in measuring the length of involved bronchus and degree of stricture in EBTB. PFT may be useful in differential diagnosis and follow up of EBTB. PMID- 11192557 TI - Pulmonary complications in patients with AIDS: a report from a Beijing hospital. AB - OBJECTIVE: The aim of this study was to improve the awareness of pulmonary complications in patients with AIDS. METHODOLOGY: Nine patients with AIDS with pulmonary involvement from March 1992 to March 2000 were analysed. RESULTS: Of the nine cases, there were eight cases complicated with Pneumocystis carinii pneumonia (PCP). The clinical presentation of PCP was fever (8/8), dyspnoea on exertion or at rest (7/8), and hypoxaemia with a mean PaO2 of 58 mmHg. Chest X ray films showed bilateral diffuse interstitial or alveolar infiltrates. Pulmonary tuberculosis, tuberculous lymphadenitis and bronchial fungal infection were found in three cases. CONCLUSIONS: AIDS patients are at high risk of suffering from pulmonary complications, of which PCP is most common. If young patients who were healthy in the past suddenly suffered from pneumonia and respiratory failure, PCP should be considered. When opportunistic pulmonary infection is diagnosed under special circumstances, one should be alert to the possibility of AIDS and examine serum antihuman immunodeficiency virus (HIV) antibody. PMID- 11192558 TI - Clinical manifestations of tuberculosis in HIV-infected patients. AB - OBJECTIVE: The purpose of the present study was to evaluate the impact of HIV infection on the clinical presentation of tuberculosis. METHODOLOGY: We retrospectively studied the impact of HIV infection on the clinical presentation of tuberculosis. A total of 60 consecutive patients co-infected with HIV and tuberculosis were identified. RESULTS: Majority were male (88.3%) and the most common transmission category was heterosexual contact (80%). Most were in the advanced stage of HIV infection; 93% had CD4 cell count less than 200/mm3. Concerning the site of tuberculosis involvement, 37% had pulmonary involvement alone, 13% had extrapulmonary disease involving one single site, 50% had both pulmonary and extrapulmonary involvement. Fifteen (25%) patients also met the criteria of disseminated tuberculosis, who had a significantly lower mean CD4 cell count than those with pulmonary involvement alone (mean 40 vs 102; P = 0.048). Chest radiographs comprised a wide spectrum of manifestations. A considerable proportion had primary pulmonary tuberculosis pattern (38%) and normal radiographs (8.5%). CONCLUSIONS: Our patients generally had advanced HIV infection; 93% of those had CD4 lymphocyte count < 200/mm3. Extrapulmonary involvement and disseminated disease were common. Radiographic manifestations of pulmonary tuberculosis were often 'atypical' due to the greater proportion of primary tuberculosis among our patients. PMID- 11192559 TI - Comparison of frequency doubling perimetry with humphrey visual field analysis in a glaucoma practice. PMID- 11192560 TI - Frequency doubling technology perimetry for detection of glaucomatous visual field loss. PMID- 11192561 TI - Rehabilitation and total hip replacement: patients' perspectives on provision. AB - This paper examines the effectiveness of the rehabilitation component of total hip replacement (THR). It focuses on contrasting rehabilitation regimes in two hospitals in the north of England. Using qualitative methods, patients' perceived needs and goals are described, and the responsiveness of the interventions to their requirements is examined. The provision of information, equipment, and therapy was found to be useful in terms of preparing patients for their operation and facilitating their recovery, but less so in terms of helping them cope with any problems experienced after the operation. Drawing on patients' perspectives, a set of guidelines for good practice in rehabilitation for THR is presented. PMID- 11192562 TI - Assessment, education and placement: an integrated approach to vocational rehabilitation. AB - Taking into account that a great number of people in the Netherlands are considered incapacitated for work, reintegration activities are becoming increasingly important. Thus far, no studies have been conducted in the Netherlands to investigate the long-term effectiveness of vocational rehabilitation programmes. This study assessed the long-term effectiveness of the programmes of three vocational rehabilitation centres. The centres relate their success to the proportion of trainees participating in the competitive labour market. The centres provide integrated programmes in certified occupational training and personal skills training. After five years, 80% of the trainees are working in the competitive labour market. In addition, their personal skills have improved. Within 4 to 7 years the decrease in social security costs of reintegrated employees will outweigh the total costs of the vocational training programme. PMID- 11192563 TI - Multidisciplinary vocational rehabilitation focusing on work training and case management for unemployed sick-listed people. AB - Twenty-four unemployed sick-listed people were referred during 1996 and 1997 to a multidisciplinary vocational rehabilitation programme with additional work training and case management. Twelve months after the programme, 54.2% in the study group had lowered their benefit levels compared with those at the start while 26.1% in the control group - who underwent a conventional rehabilitation programme - had lowered their benefit levels (p = 0.050, Chi-squared test). There were no significant differences regarding fewer sick days three and 12 months after the programme between the study group and the control group. Regarding self assessed quality of life, there were no significant differences within or between the groups. We conclude that this multidisciplinary vocational rehabilitation programme with work training and case-management affected the outcome positively regarding lowered level of benefits 12 months after termination of programme compared with level at start. Studies of the long-term effect of the programme should, however, be performed with more subjects in both study group and control group. PMID- 11192564 TI - Factors indicating need of rehabilitation--occupational therapy among persons with long-term and/or recurrent pain. AB - The aim of the study was to elucidate selection criteria for need of rehabilitation/occupational therapy, and to state criteria for participation in occupational therapy, among persons with long-term and/or recurrent pain causing activity limitations or restricting participation in daily life. The study involved 914 persons aged 18-58 years who answered a postal questionnaire concerning demography, pain, occupations in daily life, work, treatments and health care staff visited. The direct method in logistic regression analysis was used to test two models: (1) need of rehabilitation/occupational therapy and (2) participation in occupational therapy. The results for the first model revealed the selection criteria (1) 'feelings of irresolution', (2) 'gnawing/searing pain' and (3) 'use of technical aids'. The odds for need of rehabilitation/occupational therapy were higher for women than for men. The criteria derived from the second model, participation in occupational therapy, were whether (1) the participants had 'used tricks and/or compensated ways to perform tasks', (2) the participants had 'pain in shoulders' and (3) 'changes had been made at work due to health conditions'. PMID- 11192565 TI - Information needs of families when one member has a severe brain injury. AB - Despite calls for health and social services to respond to the needs of informal carers, there is little evidence to guide practioners in the best way to provide support and/or information in situations of complex need such as brain injury. This study addressed such an intervention in a prospective descriptive study, using both qualitative and quantitative methodology. Eighty-nine patients who had been admitted to a regional neurorehabilitation unit for management of traumatic or haemorrhagic brain injuries were consecutively discharged to the community over a period of 12 months. Eighty-two of these people identified a carer who agreed to be interviewed at approximately six weeks after discharge regarding their concerns. The study identified that even soon after discharge from inpatient rehabilitation, carers wanted more information. In many cases the need for information was unrelated to either the severity of injury or level of functional deficit. In addition, requests for information were in many cases not sought spontaneously, but required prompting. Such findings have implications if interventions in this field are to have the optimum chance of succeeding in providing support and assistance. PMID- 11192566 TI - Attitudes of community-living staff toward the integration of persons with mental retardation in the community. AB - The present study was conducted to determine the extent to which the current philosophical approach of inclusion and integration in the community of persons with mental retardation is embodied in the attitudes of staff members who are charged with implementing it. The research sample was comprised of 106 staff members who work in three major geographical districts of community-living settings in Israel. Overall, the results suggest that a true understanding of and agreement with this philosophy is far from being achieved. The findings of this study provide evidence that staff members charged with providing services and support to persons with mental retardation have not fully adopted the attitudes of the community-living approach. Findings are interpreted in relation to practice. PMID- 11192567 TI - Hearing-impaired students' reading characteristics compared to dyslexic students (tested in Hebrew). PMID- 11192568 TI - Guided exploration enhances tactual picture recognition in blindfolded sighted children: implications for blind children. PMID- 11192569 TI - The use of virtual reality to train powered wheelchair users and test new wheelchair systems. PMID- 11192570 TI - Family rehabilitation of psychiatric patients: a study of course of involuntary admissions to a psychiatric hospital. PMID- 11192571 TI - Rehabilitation psychiatry--description of a pioneering facility in Pakistan. PMID- 11192572 TI - Excerpts of an Executive Summary of Research and Evaluation of the International Leadership Forum for Women with Disabilities (ILFWD), Bethesda, MA, USA, 1997. PMID- 11192573 TI - Neuroendocrine cell-specific expression and regulation of the human secretogranin II gene. PMID- 11192574 TI - Characterization of chromogranins in the frog Rana ridibunda. Structure, expression, and functional implications. PMID- 11192575 TI - Expression of equine chromogranin A. CDNA sequence and distribution of mRNA in endocrine and exocrine tissues. PMID- 11192576 TI - Salivary secretion of chromogranin A. Control by autonomic nervous system. PMID- 11192578 TI - Endothelial handling of chromogranin A. PMID- 11192577 TI - Proteolytic processing of chromogranins. PMID- 11192579 TI - Tissue plasminogen activator and chromaffin cell function. PMID- 11192580 TI - Chromogranin A immunoreactivity in neuroendocrine cells in the human gastrointestinal tract and pancreas. PMID- 11192581 TI - Chromogranin A and its derived peptides in the rat and porcine gastro-entero pancreatic system. Expression, localization, and characterization. PMID- 11192582 TI - Chromogranins: current concepts. Structural and functional aspects. PMID- 11192583 TI - Regulation of parathyroid secretion. Chromogranins, chemokines, and calcium. PMID- 11192584 TI - Vasostatins. Vascular targets. PMID- 11192585 TI - Vasostatins. Dilators of bovine resistance arteries. PMID- 11192586 TI - Pancreastatin. Biological effects and mechanisms of action. PMID- 11192587 TI - The novel catecholamine release-inhibitory peptide catestatin (chromogranin A344 364). Properties and function. PMID- 11192588 TI - Secretoneurin--a novel link between the nervous and the immune system. Conservation of the sequence and functional aspects. PMID- 11192589 TI - Chromogranin A induces a neurotoxic phenotype in brain microglial cells. PMID- 11192590 TI - Antibacterial and antifungal peptides derived from chromogranins and proenkephalin-A. From structural to biological aspects. PMID- 11192591 TI - The chromogranins. Historical perspectives. PMID- 11192592 TI - Measurements of chromogranins and chromogranin-related peptides by immunological methods. PMID- 11192593 TI - Chromogranins as diagnostic and prognostic markers in neuroendocrine tumours. PMID- 11192594 TI - Assessment of chromogranin A using two-site immunoassay. Selection of a monoclonal antibody pair unaffected by human chromogranin A processing. PMID- 11192595 TI - Chromogranin A and tumor necrosis factor-alpha (TNF) in chronic heart failure. PMID- 11192596 TI - Chromogranin A (CGA) and the enterochromaffin-like (ECL) cell. PMID- 11192597 TI - Chromogranins in non-endocrine tumours. PMID- 11192598 TI - Chromogranin A in human disease. PMID- 11192599 TI - A physiological role for the granins as prohormones for homeostatically important regulatory peptides? A working hypothesis for future research. PMID- 11192600 TI - Signal-mediated sorting of chromogranins to secretory granules. PMID- 11192601 TI - The condensed matrix of mature chromaffin granules. The soluble form of dopamine beta-hydroxylase is catalytically inactive. PMID- 11192602 TI - Functional role of chromogranins. The intragranular matrix in the last phase of exocytosis. PMID- 11192603 TI - Inositol 1,4,5-trisphosphate receptor and chromogranins A and B in secretory granules. Co-localization and functional coupling. PMID- 11192604 TI - Regulation of chromogranin A transcription and catecholamine secretion by the neuropeptide PACAP. Stimulation and desensitization. PMID- 11192605 TI - The neuronal survival effects of rasagiline and deprenyl on fetal human and rat ventral mesencephalic neurones in culture. AB - The neuronal survival properties of rasagiline (R(+)-N-propargyl-1-aminoindane mesylate or TVP-1012), a novel monoamine oxidase B inhibitor, have been investigated using neuronal cell cultures from fetal rat and human ventral mesencephalon. The ability of rasagiline to reduce the rate of neuronal cell loss in vitro was tested using primary neuronal cell lines and immunohistochemistry to quantify the reduction in cell death. Direct comparison was made with deprenyl, a widely used and long established monoamine oxidase B inhibitor. Rasagiline was shown to act 15-20% more effectively as a neuronal survival agent than deprenyl, increasing both the survival of the total number of neurones and selectively increasing the survival of dopaminergic neurones with no statistically significant increase in survival of GABAergic neurones. PMID- 11192606 TI - Intraventricular galanin produces a time-dependent modulation of 5-HT1A receptors in the dorsal raphe of the rat. AB - Galanin given i.c.v. increased the K(D) values of 5-HT1A receptors in the DR by 100% 10 min after administration. This effect had disappeared 2 h and 5 h after galanin administration. In contrast, i.c.v. galanin caused a 40% increase in the Bmax values at 2 h without affecting the Bmax values 10 min and 5 h after i.c.v. galanin. The mRNA levels of 5-HT1A receptors and of galanin in the DR were significantly decreased by 33% and 56% respectively 2h but not 5h after i.c.v. galanin. These results suggest that in vivo galanin can modulate somatodendritic 5-HT1A receptors in the DR in a time-dependent manner via galanin-5-HT1A receptor interactions. The findings implicate a potential role of galanin in affective disorders. PMID- 11192607 TI - Temperature set-point changes induced by DA D2/3 and 5-HT1A receptor agonists in the rat. AB - The DA D2/3 receptor agonist 7-OH-DPAT (2 micromol kg(-1)) and the 5HT1A receptor agonist 8-OH-DPAT (0.6 micromol kg(-1)) both produced a marked and similar decrease in core temperature of 3-4 degrees C at 10 and 20 degrees C ambient temperature. At 30 degrees C there were no, or weak, effects. The decrease in core temperature was accompanied by a sudden increase in tail temperature, followed by a decrease as core temperature returned to basal values. The results suggest that the hypothermia produced by the respective DA D2/3 and the 5-HT1A receptor agonists 7-OH-DPAT and 8-OH-DPAT is an active process, in all probability due to changes in a hypothalamic set-point for temperature regulation. PMID- 11192608 TI - Locomotor activity and a conditioned fear response: correlation with cortical and subcortical binding of the dopamine D1 receptor antagonist. AB - Rat behavior in the open field and conditioned fear response test was correlated with specific binding of dopamine D1 receptor antagonist [3H]SCH 23390 within different brain structures assayed with autoradiography. A significant positive correlation was found between the ligand binding in the substantia nigra pars reticulata and both animal motor activity (r = 0.67, p < 0.05) and the number of entries into the central sector of the open field (r = 0.59, p < 0.05). On the other hand, rat motility and the central entries were negatively correlated with [3H]SCH 23390 binding within the caudate putamen (r = -0.64, p < 0.05 and r = 0.61 p <0.05, respectively). No correlation was revealed between the ligand binding in the examined brain areas and freezing reaction in the contextual fear conditioning test. The present data indicate for the first time a significant, structure-dependent correlation between rat motor behavior and the dopamine D1 receptor ligand binding within the nigrostriatal system. PMID- 11192609 TI - Cortical activation evoked by visual mental imagery as measured by fMRI. AB - One of the major controversies in cognitive neuroscience is whether the primary visual cortex and nearby areas are involved in visual mental imagery. In an fMRI study we examined the brain activity of 10 healthy subjects under different task conditions: in the perception condition subjects saw complex geometrical shapes and had to decide whether other highlighted stimuli fell inside or outside the figure. In the imagery condition subjects saw only the highlighted stimuli and were instructed to imagine the previously studied geometrical shapes to solve the same task. Although the behavioral data show a distance effect that would be expected based on topographically organized mental images, the functional imaging data do not show increased activity in the primary visual cortex in the imagery condition. In the occipital cortex a slightly increased activity was found only in the visual association cortex (BA 19), whereas the highest activation was observed in the parietal cortex (BA 7 and 40). The results of the study do not support the assumption that the primary visual cortex is involved in visual mental imagery, but rather that a network of spatial subsystems and higher visual areas appears to be involved. PMID- 11192610 TI - Modulated expression of secreted frizzled-related proteins in human retinal degeneration. AB - Inherited retinal degenerations such as retinitis pigmentosa (RP) are characterized by progressive loss of photoreceptors, apparently by apoptosis, and our recent report of increased secreted Frizzled-related protein-2 (SFRP2) in RP retinas suggests altered Wnt signalling may be a component of the degenerative process. The present study shows that levels of SFRPI, SFRP3 and SFRP5 mRNAs are also abnormal in RP, giving rise to idiosyncratic expression patterns. In highly degenerative retinas, the SFRP proteins localize mainly to the inner limiting membrane, but in a well-preserved retina SFRPI and SFRP5 are notably localized to the surviving photoreceptors. Together with increased c-jun mRNA expression in all cases examined, these results support the notion that disruptions of Wnt network signalling are involved retinal neurodegeneration. PMID- 11192611 TI - Corticosteroids protect oligodendrocytes from cytokine-induced cell death. AB - The present data show that the simultaneous exposure to tumor necrosis factor alpha (TNFalpha) and interferon-gamma (IFNgamma) induces cell death with characteristics of apoptosis in cultured rat oligodendrocytes; TNFalpha alone was ineffective. We have also demonstrated that different corticosteroids (aldosterone, deoxycorticosterone, dexamethasone and corticosterone) protect rat oligodendrocytes in culture from apoptosis induced by TNFalpha plus IFNgamma. This effect seems to be exerted via the interaction with both type I and type II corticosteroid receptors since all steroids considered are effective. Since oligodendrocyte apoptosis represents an important event in multiple sclerosis and in several demyelinating diseases, the present observations might be considered an interesting background for further researches directed to the possibility of controlling in vivo the death of these cells. PMID- 11192612 TI - The use of a recombinant lentiviral vector for ex vivo gene transfer into the rat CNS. AB - A major obstacle in ex vivo gene transfer has been the loss of transgene expression soon after implantation of the grafted transduced cells. Recently, a lentiviral vector system has been developed which has proven to express high levels of transgenes in vivo after direct injection into the tissue. In this study, we have investigated the use of such a vector for ex vivo gene transfer to the brain. A number of neural cell types were found to be permissive to transduction by the lentiviral vector in vitro and a majority of them expressed the transgene after transplantation to the rat brain. Transgene expression was detected up to 8 weeks post-grafting. These findings suggest that recombinant lentiviral vectors may be used for further development of ex vivo gene therapy protocols to the CNS. PMID- 11192613 TI - Magnetic resonance imaging of the membranous labyrinth during in vivo gadolinium (Gd-DTPA-BMA) uptake in the normal and lesioned cochlea. AB - MRI with a T1 contrast agent was used to investigate the normal and noise-damaged cochlea. The time course and distribution of the in vivo uptake of the gadodiamide chelate bound paramagnetic Gd ion (GdDTPA-BMA) throughout the membranous labyrinth of normal and impulse noise-damaged guinea pig cochleae were measured by MRI at 4.7T. Simultaneous signal enhancement of the basal, medial and apical scala tympani (ST) and scala vestibuli (SV) was observed within 10 min following i.v. injection, reaching maximum levels at around 100 min. ANOVA and post hoc paired t-tests showed statistically significant differences in the levels and rates of Gd uptake-enhancement between the scalae. The ST revealed the most rapid and extensive enhancement throughout the period of active Gd uptake, while the SV showed comparatively slower and less enhancement, and the intact scala media (SM) indicated insignificant enhancement. The in vivo Gd penetration and enhancement of the membranous SM increased significantly in the noise-damaged cochlea, suggesting lesioning of the cochlear membranes. PMID- 11192614 TI - Skewing of the brain midline in schizophrenia. AB - Our laboratory has observed marked craniofacial dysmorphology along the frontonasal-maxillary juncture in schizophrenic probands and their relatives. Embryologic fate-mapping studies relate this craniofacial juncture to the diencephalic-mesencephalic border, and on the basis of this correspondence we have predicted brain midline maldevelopment arising at this border in schizophrenia. Analysis of magnetic resonance images has borne out this prediction, with midline deviation scores in schizophrenia exceeding control values. High deviation scores were also observed among the siblings of these schizophrenic patients. Further, brain and face dysmorphology scores cohered within subjects, supporting this embryologically derived model. PMID- 11192615 TI - Phase-locked responses to pure tones in guinea pig auditory cortex. AB - Phase-locked responses to pure tones are a characteristic of most auditory cells at the level of the brain stem and allow sophisticated analyses based on coincidence detection. Phase-locking to tones has not previously been shown at the level of the auditory cortex in single unit studies. We have now identified phase-locked responses in 10% of low-frequency (< 1 kHz) units in the ventrorostral belt, a strip of cortex immediately ventral to the primary auditory area. All of these units showed phase-locking in their response to binaural tone pips of 60-200 Hz and showed narrow band pass characteristics within this range. PMID- 11192616 TI - Two circadian oscillatory mechanisms in the mammalian retina. AB - To investigate the mechanism that controls circadian rhythms in the mammalian retina, we examined the mRNA expression rhythms of serotonin N-acetyltransferase (NAT), the mammalian clock gene rPer2 and a clock-controlled gene Dbp in the retina of rats with lesions of the suprachiasmatic nucleus (SCN), the master clock in mammals. Northern blot analyses showed that retinal NAT mRNA still exhibited the circadian expression in the SCN-lesioned rats, whereas the lesion abolished the rhythms of rPer2 and Dbp mRNAs. These findings suggest that the mammalian retina has two circadian oscillatory mechanisms: one can generate rhythmicity independent of the SCN and the other requires the SCN to maintain circadian oscillation. PMID- 11192617 TI - CNTF promotes the regrowth of retinal ganglion cell axons into murine peripheral nerve grafts. AB - Autologous peripheral nerves were transplanted onto transected optic nerves of adult mice. We examined whether intraocular CNTF injections increased retinal ganglion cell (RGC) axon regeneration, and what types of RGCs regrew axons into grafts. After temporal CNTF eye injections there were more fluorogold-labelled regenerating RGCs (mean +/- s.e.m. 342+/-113.1; n=6) than in sham eye-injected mice (133+/-27.6; n=8). Greater numbers of regenerating RGCs (1198+/-367.6; n=6) were seen in mice receiving both nasal and temporal CNTF injections. The range of soma areas in regenerate and normal retinas was similar but the average size of regenerating RGCs was greater (212 microm2 vs 111 microm2). Most regenerating RGCs had large dendritic fields. The data suggest a heterogeneous response to axotomy in adult mice, large RGCs preferentially regrowing axons into PN grafts. PMID- 11192618 TI - Basal expression of bradykinin B1 receptor in peripheral sensory ganglia in the rat. AB - The bradykinin B1 receptor is thought to be induced by tissue injury and inflammation. In the present study, we have investigated whether there is a basal expression of B1 receptor in dorsal root ganglion (DRG) and trigeminal ganglion neurons in rats. A substantial number of neurons in both DRGs and trigeminal ganglia were found to be B1-immunoreactive in rats. Both small and medium-sized DRG neurons were B1-immunoreactive, suggesting that they are likely to be Adelta- or C-fibre neurons which are involved in nociceptive transmission. These results support a possible role for B1 receptors in the modulation of nociceptive sensory transmission. PMID- 11192619 TI - Calpain inhibitor inhibits secretory granule maturation and secretion of GH. AB - Clathrin- and AP-1-coated buds are present on immature secretory granules of endocrine cells that mature into clathrin-uncoated granules. The mechanism of clathrin and adaptor protein uncoating has remained obscure. Benzyloxycarbonyl-L leucyl-L-leucinal (ZLLal), a calpain inhibitor, reduced growth hormone (GH) secretion with intracellular accumulation, in a GH-secreting rat pituitary tumor cell. Pulse and chase demonstrated that ZLLal retarded the turnover of clathrin (Clt.H) and adaptins. ZLLal-treatment co-immunoprecipitated the increased amounts of GH with Clt.H and adaptins compared to control cells, suggesting the intracellular accumulation of immature secretory granules. Clt.H and adaptins were limited-proteolyzed by m-calpain in vitro, indicating that calpain may be involved partly in the maturation of secretory granules in endocrine cells via the process of clathrin uncoating. PMID- 11192620 TI - High frequency repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex in schizophrenic patients. AB - Repetitive transcranial magnetic stimulation (rTMS) has been tried therapeutically in major depression. In order to investigate the therapeutic efficacy of rTMS in psychotic patients, 12 participants (four women, eight men) with schizophrenia according to DSM-IV criteria, aged 25 to 63 years (mean (+/ s.d) 40.4+/-11.0), were enrolled in the study. Following a double-blind crossover design, patients were treated at random with 2 weeks of daily left prefrontal rTMS (20 2s 20 Hz stimulations at 80% motor threshold over 20 min, dorsolateral preforntal cortex) and 2 weeks of sham stimulation. The Brief Psychiatric Rating Scale decreased under active rTMS (p <0.05), whereas depressive symptoms (BDI) and anxiety (STAI) did not change significantly. Prefrontal rTMS might be effective in the non-pharmacological treatment of psychotic patients. PMID- 11192621 TI - Differential impact of periodic and aperiodic speech-like acoustic signals on magnetic M50/M100 fields. AB - Voiced and unvoiced sounds, characterized by a periodic or aperiodic acoustic structure, respectively, represent two basic information-bearing elements of the speech signal. Using whole-head magnetencephalography (MEG), magnetic fields (M50/M100) in response to synthetic vowel-like as well as noise-like signals matched in spectral envelope were recorded in 20 subjects. Aperiodic events gave rise to increased M50 concomitant with reduced M100 activity as compared to their periodic cognates. Attention toward the auditory channel enhanced the effects of signal periodicity. These data provide first evidence that speech-relevant acoustic features differentially affect evoked magnetic fields as early as the M50 component. Conceivably, the M50 field reflects an ongoing monitoring process whereas the M100 component is bound to more specific operations such as detection of signal periodicity. PMID- 11192622 TI - Lesion-induced changes in NMDA receptor subunit mRNA expression in rat visual cortex. AB - Focal lesions in the visual cortex are well known to induce pronounced perilesional reorganization of the neuronal circuitry. Since NMDA receptors crucially control synaptic plasticity and reorganization, we studied lesion induced changes in their subunit expression and biophysical properties. Between 8 and 10 days after focal thermolesioning, pyramidal neurones in the near surround of the lesion were studied in acute brain slices. We found a significant decrease in the ratio of NR2A and NR2B subunit mRNA as compared to neurones from sham operated animals. Interestingly, no significant differences in the properties of NMDA receptor-mediated postsynaptic currents (NMDA PSCs) were observed between lesioned and sham operated animals. Thus, the observed perilesional changes in the NR2A/NR2B mRNA ratio appear to be subthreshold to result in significant changes in the functional properties of NMDA receptors. PMID- 11192623 TI - Evidence for proportional synaptic scaling in neocortex of intact animals. AB - Neocortical neurons in culture can modify their global synaptic strength according to their recent activity level. This process has been termed synaptic scaling. We explored possible effects of synaptic scaling in intact animals by comparing EPSPs of two identified synaptic tracts on single cortical neurons in acute slices. We show that the amplitude and rise-time of unitary thalamocortical and intracortical EPSPs vary among different neurons, but are highly correlated on single cells. Likewise, the AMPA-to-NMDA receptor ratio in EPSPs evoked from the two tracts is correlated in single neurons, although intracortical pathways within layer 5 exhibit a significantly larger NMDA component. These findings demonstrate that, under physiological conditions, cortical neurons actively regulate their own response magnitude, regardless of the input source. PMID- 11192624 TI - Elevated plasma levels of transforming growth factor beta1 in patients with muscular dystrophy. AB - The progression of muscular weakness of patients suffering from muscular dystrophies directly correlates with the progressive loss of myofibers, accompanied by fibrosis. Since transforming growth factor beta1 (TGF-beta1) promotes tissue fibrosis, we measured the plasma TGF-beta1 level in patients with various muscular dystrophies in order to determine whether the level is elevated in patients with muscular dystrophy and if the level reflects the severity of tissue fibrosis. The plasma TGF-beta1 level was significantly elevated in patients with Duchenne muscular dystrophy and congenital muscular dystrophy (CMD), but not in those with Becker muscular dystrophy. Growth factors related to muscle fiber regeneration and fibrosis might be a key factor in the progression of muscular dystrophy and could be a target for therapeutic studies. PMID- 11192625 TI - The effect of autonomic arousal on attentional focus. AB - This study investigates the effect of arousal on visual selection processes. Arousal is predicted to narrow the window of attention surrounding a point of focus. BOLD response to a letter discrimination task was measured under aroused (aversive noise) and non-aroused conditions (n = 8). Results revealed spatially distinct responses for trials invoking a narrow versus wide attentional focus. Under arousal a wide focus showed posterior thalamic activation similar to that associated with the narrowed attentional focus. This reflects altered stimulus filtering and supported the hypothesis. Relevant neuroanatomy involving the locus coeruleus and a triangular circuit of selective attention is discussed. The data demonstrates the intersection of arousal and visual stimulus selection systems, identifies a cognitive consequence of arousal, and provides the first fMRI evidence for brain stem autonomic arousal. PMID- 11192626 TI - Dopaminergic regulation of synaptotagmin I and IV mRNAs in hemiparkinsonian rats. AB - Synaptotagmins (Syts) I and IV are synaptic proteins involved in the regulation of neurosecretion. Dopaminergic drugs have been shown to modulate their expression. Here we investigate whether dopaminergic regulation of syt I and syt IV expression could play a role in the hypersensitive striatum of rats with unilateral lesions of dopaminergic nigrostriatal neurons with 6-hydroxydopamine. We show that chronic dopaminergic denervation resulted in a small down-regulation of striatal syt I mRNA, whereas acute treatment with SKF-82958, a dopamine D1 receptor agonist, induced a massive syt IV mRNA upregulation in the striatum on the lesioned side. We conclude that chronic lack of dopamine and treatment with dopamine D1 receptor agonists alter the synaptic plasticity in dopamine depleted basal ganglia. PMID- 11192627 TI - Leptin and TGF-beta synergistically regulate VIP cytokine response element transcription. AB - Leptin was originally described as an adipocyte-derived cytokine that signals to the hypothalamus to regulate food intake and energy expenditure. Leptin signals through the Ob receptor, which is closely related to the gp130 cytokine receptor. Here we show that leptin can induce expression of the neuropeptide gene vasoactive intestinal peptide (VIP) through the VIP cytokine response element, the same element that mediates the response to the gp130 cytokines. Leptin acts synergistically with TGF-beta to activate transcription through this element. Transcriptional responses to leptin are increased when transmitted through ObR mutated at Tyr986, the SHP-2 docking domain, yet this mutation does not alter the synergy between TGF-beta and leptin. These data emphasize the functional similarity between leptin and the gp130 cytokines. PMID- 11192628 TI - Facilitation of NMDA-induced currents and Ca2+ transients in the rat substantia gelatinosa neurons after ligation of L5-L6 spinal nerves. AB - This study employing a rodent model of neuropathic pain investigated the influence of partial nerve injury on the ability of NMDA receptor activation to induce membrane currents and rises in cytosolic concentration of free calcium ([Ca2+]i) in the rat substantia gelatinosa (SG) neurons using simultaneous whole cell patch-clamp recording and fura-2 calcium imaging in spinal slices. The novel findings are that: (I) L5-L6 spinal nerve ligation produces a sustained facilitation of NMDA-mediated membrane currents and [Ca2+]i rises both in the soma and dendrites of SG neurons on the injured side on post-operative days 4-13 after injury. (2) It appears that SG neurons in slices from injured rats recover from Ca2+ load less efficiently than neurons from naive rats. (3) The membrane depolarization-induced Ca2+ transients in SG neurons are not modified following spinal nerve ligation. The temporal profile of the changes in Ca2+ transients correlated well with the development of mechanical and thermal allodynia and hyperalgesia. These results suggest an important role of NMDA-mediated calcium signalling in the pathogenesis of neuropathic pain following spinal nerve injury. PMID- 11192629 TI - Motor activity-mediated partial recovery in ischemic rats. AB - Spontaneous partial recovery in motor and/or cognitive dysfunctions in stroke patients has been documented, but the factors that affect such functional improvement have not been well elucidated. The present study demonstrates that repeated behavioral testing (daily or once a week over a period of 4 weeks) promoted partial recovery from motor asymmetry in adult ischemic rats. In contrast, ischemic animals that were only tested once every 2 weeks or once after 4 weeks did not show such partial recovery. These results suggest that repeated behavioral testing (i.e., increased use of the ischemia-affected limbs and body parts) may contribute to partial recovery of motor deficits following an experimental stroke, even in the absence of pharmacological therapeutic intervention. PMID- 11192630 TI - GDNF and neublastin protect against NMDA-induced excitotoxicity in hippocampal slice cultures. AB - The potential neuroprotective effects of glial cell line-derived neurotrophic factor (GDNF) and neublastin (NBN) against NMDA-induced excitotoxicity were examined in hippocampal brain slice cultures. Recombinant human GDNF (25-100 ng/ ml) or NBN, in medium conditioned by growth of transfected, NBN-producing HiB5 cells, were added to slice cultures I h before exposure to 10 microM NMDA for 48h. Neuronal cell death was monitored, before and during the NMDA exposure, by densitometric measurements of propidium iodide (PI) uptake and loss of Nissl staining. Both the addition of rhGDNF and NBN-containing medium significantly reduced the NMDA-induced PI uptake in the CA1 (p < 0.01), suggesting neuroprotective effects of these factors, beyond their well-known trophic effects on dopaminergic neurons. PMID- 11192631 TI - Information processing in the spinocerebellar system. AB - The purpose of this study was to determine whether sensory information about limb kinematics relayed to the cerebellum over spinocerebellar pathways may be modified at the cerebellar level. We tested this by recording from dorsal spinocerebellar tract (DSCT) and Purkinje cells under the same experimental conditions in which the hindlimbs of anesthetized cats were passively moved through a series of step-like movement cycles. A population analysis of the response behavior showed that DSCT neurons encode a combination of limb axis position and movement velocity, whereas the Purkinje cells located in the DSCT cerebellar target areas encode limb axis velocity and position independently. We conclude from this that the cerebellum may somehow extract a velocity component from the afferent input signal. PMID- 11192632 TI - Temporal encoding in auditory evoked neuromagnetic fields: stochastic resonance. AB - Recent investigations have demonstrated that temporal patterns of sensory neural activity detected by magnetoencephalography (MEG) reflect features of the stimulus. In this study, neuromagnetic activity was investigated using an event detection algorithm based on the correlation coefficient. The results of the technique are compared with widely used methods of analysis in two experimental conditions and are shown to identify features in the single-trial MEG response that are not apparent in the response obtained by averaging across repeated trials. As an example of the technique, the physiologic jitter in latency associated with the M100 of auditory evoked fields was reproducibly measured. Specifically, higher intensity sounds were associated with an increased reliability. The technique was also applied to the noise-enhanced evoked auditory response, producing an objective demonstration of a cortical manifestation of the phenomenon of stochastic resonance-the paradoxical enhancement in the measurement of the signal-to-noise ratio (SNR) induced by optimal addition of noise to system input. PMID- 11192633 TI - Concussions in athletes produce brain dysfunction as revealed by event-related potentials. AB - We have used event-related potentials (ERP) to assess cerebral activity following mild traumatic brain injuries in 20 college athletes practising contact sports. Concussion victims showed a striking decrease in P300 amplitude, an effect presumed to reflect alterations in attentional-cognitive processes. Moreover, the degree of impairment was strongly related to the severity of post-concussion symptoms. Our data suggest that concussions cause objectively measurable changes in the electrophysiological markers of brain activity and hence in the functions of the structures from which they originate. ERPs may thus constitute a reliable method to accurately monitor the clinical course and recovery of head injuries in athletes. PMID- 11192634 TI - Lexical retrieval during fluent speech production: an fMRI study. AB - We investigated the neural correlates of lexical retrieval during fluent speech production using fMRI. Blood oxygenation level dependent (BOLD) contrast was measured while subjects spoke about 7 Rorschach inkblots for 3 min each. Varying degrees of speech rate were elicited during each run. In a within-subject design, the number of words produced was correlated with the BOLD contrast in the two runs in each subject that showed the highest variance of speech output. The rate of articulation was positively correlated with activation in the left superior temporal (BA 22) and supramarginal (BA 39/ 40) gyri. The main negative correlations were in the fusiform gyri bilaterally (BA 19), the posterior cingulate (BA 30) and superior occipital gyrus (BA 19). Lexical retrieval during continuous language production engages areas in the left temporal and inferior parietal cortex. This pattern of activation differs from that evident during the generation of single words (verbal fluency), which is more associated with left prefrontal activation. PMID- 11192635 TI - Startle responses, heart rate, and temperature in 5-HT1B receptor knockout mice. AB - Relative to wildtype mice, mice lacking 5-HT1B receptors (5-HT1B KO) exhibit exaggerated heart rate and body temperature responses to environmental stimuli. In contrast, acoustic startle reactivity is reduced in 5-HT1B KO mice. We combined heart rate and temperature measurement with startle response paradigms in order to elucidate this apparent contradiction. Habituation and footshock induced sensitization paradigms modulate startle reactivity. Reduced startle reactivity and unaltered habituation in 5-HT1B KO mice were replicated. Heart rate and temperature were unaffected by startle stimuli, but increased markedly in response to transportation and handling procedures. Footshocks caused a mild startle-sensitization and tachycardia in both genotypes. The physiological hyper reactivity in 5-HT1B KO mice is a subtle phenotypic difference that contrasts with the phenotypic decrease in startle reactivity. PMID- 11192636 TI - Assembly of functional alpha6beta3gamma2delta GABA(A) receptors in vitro. AB - Transgenic mice deficient in the alpha6 subunit of the GABA(A) receptor show reduced levels of the delta subunit protein and an altered GABA(A) receptor pharmacology, suggesting selective assembly mechanisms. Delta reduced the binding of [3H]Ro15-4513 or t-butylbicyclophosphoro[35S]thionate and, to a lesser extent, [3H]muscimol to recombinant alpha1beta1gamma2(delta), alpha4beta1gamma2(delta) and alpha6beta1gamma2(delta) receptors, paralleled by diminished GABA-evoked maximal currents in electrophysiological recordings for the latter one. The delta subunit gave rise to a lower EC50 for GABA and a slowed desensitization indicating its assembly in alpha6beta2delta, alpha6beta1gamma2delta and alpha6beta2gamma2delta receptors. The data show that the delta subunits assemble in various functional GABA(A) receptor subtypes in vitro to reduce GABA-evoked maximal currents and ligand binding, but increase the potency for GABA. PMID- 11192637 TI - Stem cell research--will further work be permitted? PMID- 11192638 TI - Who to support tropical disease research programmes in Africa. PMID- 11192639 TI - Genetic studies in Drosophila: vesicle pools and cytoskeleton-based regulation of synaptic transmission. AB - Presynaptic plasticity mechanisms rely on modulation of the synaptic vesicle fusion machinery and the regulated mobilization of synaptic vesicles at the active zone. This review discusses recent evidence suggesting that the relative proportions of synaptic vesicles in the reserve and ready releasable pools is the primary determinant of synaptic transmission strength, and that transport of vesicles between these pools is mediated by cytoskeletal mechanisms. Recent efforts to identify the molecules required for regulation of the presynaptic cytoskeleton suggest that common mechanisms may exist to regulate synaptic vesicle pools in widely divergent neuronal types, ranging from synaptic modulation at the Drosophila neuromuscular junction to the synaptic plasticity required for learning and memory in the mammalian brain. PMID- 11192640 TI - Leadership and fecal coliforms: Walkerton 2000. PMID- 11192641 TI - About those waiting lists.... PMID- 11192642 TI - About those waiting lists.... PMID- 11192643 TI - Competency of adolescents to make informed decisions. PMID- 11192644 TI - Beta-blockers as first-line therapy for hypertension. PMID- 11192645 TI - Unintended subcutaneous and intramuscular injection by drug users. PMID- 11192646 TI - An author by any other name. PMID- 11192647 TI - Secular trends in the body mass index of Canadian children. AB - BACKGROUND: Various changes in society have created the opportunity for more sedentary behaviour and the consumption of food that is high in kilojoules, which may lead to a progressive increase in body mass over time. The purpose of this study was to examine secular changes in the body mass index (BMI) of Canadian children between 1981 and 1996. METHODS: Nationally representative data from the 1981 Canada Fitness Survey, the 1988 Campbell's Survey on the Well-being of Canadians and the 1996 National Longitudinal Survey of Children and Youth were used in the analysis. Regression analyses were used to assess population changes in BMI from 1981 to 1996 for children aged 7-13 years. Changes in the distribution of BMI results were evaluated by plotting the residuals from regression analyses of BMI on age, assessed separately by sex, using the 1981 data as baseline. The proportions of children exceeding the 85th and 95th age- and sex-specific percentiles from the 1981 (baseline) data were also calculated. RESULTS: Since 1981, BMI has increased at the rate of nearly 0.1 kg/m2 per year for both sexes at most ages, indicating a clear secular trend toward an increase in BMI of Canadian children. The prevalence of overweight among boys increased from 15% in 1981 to 28.8% in 1996 and among girls from 15% to 23.6%. The prevalence of obesity in children more than doubled over that period, from 5% to 13.5% for boys and 11.8% for girls. INTERPRETATION: Secular trends indicate that Canadian children aged 7-13 years are becoming progressively overweight and obese. PMID- 11192648 TI - The economic burden of physical inactivity in Canada. AB - BACKGROUND: About two-thirds of Canadians are physically inactive. As a risk factor for several chronic diseases, physical inactivity can potentially be a substantial public health burden. We estimated the direct health care costs attributable to physical inactivity in Canada, the number of lives lost prematurely each year that are attributable to a sedentary lifestyle and the effect that a reduction of 10% in inactivity levels (a Canadian objective for 2003) could have on reducing direct health care costs. METHODS: We calculated summary relative risk (RR) estimates from prospective longitudinal studies of the effects of physical inactivity on coronary artery disease, stroke, colon cancer, breast cancer, type 2 diabetes mellitus and osteoporosis. We then computed the population-attributable fraction (PAF) for each illness from the summary RR and the prevalence of physical inactivity (i.e., 62%) and applied the PAF to the total direct health care expenditures for 1999 and to the number of deaths in 1995 associated with each disease to determine the health care costs and lives lost prematurely that were directly attributable to physical inactivity. RESULTS: About $2.1 billion, or 2.5% of the total direct health care costs in Canada, were attributable to physical inactivity in 1999. A sensitivity analysis (simultaneously varying each of the health care costs and PAF by +/- 20%) indicated that the costs could be as low as $1.4 billion and as high as $3.1 billion. About 21,000 lives were lost prematurely in 1995 because of inactivity. A 10% reduction in the prevalence of physical inactivity has the potential to reduce direct health care expenditures by $150 million a year. INTERPRETATION: Physical inactivity represents an important public health burden in Canada. Even modest reductions in inactivity levels could result in substantial cost savings. PMID- 11192649 TI - Hematologic dyscrasia associated with ticlopidine therapy: evidence for causality. AB - BACKGROUND: Several rare, potentially fatal types of hematologic dyscrasia, such as agranulocytosis, aplastic anemia, neutropenia, pancytopenia, thrombocytopenia and thrombotic thrombocytopenic purpura (TTP), have been associated with ticlopidine therapy. The extent to which ticlopidine is the causative factor has not been addressed quantitatively. METHODS: We identified 211 published case reports of hematologic dyscrasia associated with ticlopidine therapy from a MEDLINE search. We analyzed the 91 reports that could be evaluated, using the Bayesian Adverse Reaction Diagnostic Instrument to calculate the posterior probability that ticlopidine caused the hematologic dyscrasia based on epidemiologic and clinical trial data (prior odds) and case information (likelihood ratio). RESULTS: The median posterior probability values (and range) for agranulocytosis, aplastic anemia, neutropenia, pancytopenia, thrombocytopenia and TTP were 0.95 (0.53-0.98), 0.81 (0.57-0.93), 0.86 (0.75-0.96), 0.78 (0.61 0.89), 0.74 (0-0.92) and 1.0 (0.33-1.00) respectively. The posterior probability was 0.75 or greater in 82 (90%) of the case reports. INTERPRETATION: This systematic analysis provides stronger evidence to implicate ticlopidine as the causative factor in the various types of hematologic dyscrasia in most published case reports. PMID- 11192650 TI - Preventive health care, 2000 update: prevention of child maltreatment. AB - OBJECTIVES: To update the 1993 report from the Canadian Task Force on the Periodic Health Examination (now the Canadian Task Force on Preventive Health Care) by reviewing the evidence for the effectiveness of interventions aimed at preventing child maltreatment described in the scientific literature over the past 6 years. OPTIONS: Screening: a variety of techniques including assessment of risk indicators. PREVENTION: programs including home visitation; comprehensive health care programs; parent education and support, combined services and programs aimed specifically at preventing sexual abuse. OUTCOMES: Occurrence of one or more of the subcategories of physical abuse, sexual abuse, neglect and emotional abuse in childhood. EVIDENCE: MEDLINE, PSYCINFO, ERIC and several other databases were searched, experts were consulted, and published recommendations were reviewed. Original research articles and overviews that examined screening for or prevention of child maltreatment were included in the update. No meta analysis was performed because the range of manoeuvres precluded comparability. BENEFITS, HARMS AND COSTS: Because of the high false-positive rates of screening tests for child maltreatment and the potential for mislabelling people as potential child abusers, the possible harms associated with these screening manoeuvres outweigh the benefits. Two randomized controlled trials showed a reduction in the incidence of childhood maltreatment or outcomes related to physical abuse and neglect among first-time disadvantaged mothers and their infants who received a program of home visitation by nurses in the perinatal period extending through infancy. It is expected that a reduction in incidence of child maltreatment and other outcomes will lead to substantial government savings. Evidence remains inconclusive on the effectiveness of a comprehensive health care program, a parent education and support program, or a combination of services in preventing child maltreatment. Education programs designed to teach children prevention strategies to avoid sexual abuse show increased knowledge and skills but not necessarily reduced abuse. VALUES: The systematic review and critical appraisal of the evidence were conducted according to the evidence-based methodology of the Canadian Task Force on Preventive Health Care. RECOMMENDATIONS: There is further evidence of fair quality to exclude screening procedures aimed at identifying individuals at risk of experiencing or committing child maltreatment (grade D recommendation). There is good evidence to continue recommending a program of home visitation for disadvantaged families during the perinatal period extending through infancy to prevent child abuse and neglect (grade A recommendation). The target group for this program is first-time mothers with one or more of the following characteristics: age less than 19 years, single parent status and low socioeconomic status. The strongest evidence is for an intensive program of home visitation delivered by nurses beginning prenatally and extending until the child's second birthday. There is insufficient evidence to recommend a comprehensive health care program (grade C recommendation), a parent education and support program (grade C recommendation) or a combination of home based services (grade C recommendation) as a strategy for preventing child maltreatment, but these interventions may be recommended for other reasons. There is insufficient evidence to recommend education programs for the prevention of sexual abuse (grade C recommendation); whether such programs reduce the incidence of sexual abuse has not been established. VALIDATION: The members of the Canadian Task Force on Preventive Health Care reviewed the findings of this analysis through an iterative process. The task force sent the final review and recommendations to selected external expert reviewers, and their feedback was incorporated. SPONSORS: The Canadian Task Force on Preventive Health Care is funded through a partnership between the Provincial and Territorial Ministries of Health and Health Canada. PMID- 11192651 TI - The spread of the childhood obesity epidemic. PMID- 11192652 TI - Bayesian assessment of adverse drug reactions. PMID- 11192653 TI - Clinical decision rules in the emergency department. PMID- 11192654 TI - Will increasing fiscal resources promote physical fitness? PMID- 11192655 TI - Views of mental illness in Morocco: Western medicine meets the traditional symbolic. PMID- 11192656 TI - Environment and health: 6. Endocrine disruption and potential human health implications. PMID- 11192657 TI - Program description: a hospitalist-run, medical short-stay unit in a teaching hospital. AB - A hospitalist-run medical short-stay unit (MSSU) was created at a university affiliated teaching hospital in Montreal in 1989. Its primary aim was to provide efficient and high-quality care to patients requiring a brief stay in hospital for short-lived medical conditions. After evaluation in the emergency department (ED), patients judged to have acute conditions requiring a short hospital stay are admitted directly to the MSSU. Conversely, patients with more complex conditions requiring a longer stay in hospital are admitted to a clinical teaching unit (CTU). Care in the MSSU is provided by a rotating group of hospitalists. Ensuring the admission of appropriate patients during non-daytime hours was the main difficulty identified. Preliminary evaluation of the MSSU suggested that ED consultants were effective at selecting suitable patients for admission to the MSSU, because only 1 in 5 patients later required transfer to other hospital wards. The 5 most common MSSU discharge diagnoses were asthma and chronic obstructive lung disease, pneumonia, congestive heart failure, urinary tract infection and cellulitis. MSSU patients had a shorter length of stay, lower rates of in-hospital complications and lower rates of readmission within 30 days of discharge compared with CTU patients. Our hospitalist-run MSSU appears to offer a workable system of health care delivery for patients with acute, self limited illness requiring a brief stay in hospital. The MSSU appeared to promote the efficient use of hospital beds without compromising patient outcomes, however, further research is required to compare the efficiency and outcomes of care directly with that provided by the traditional CTU system. PMID- 11192658 TI - Bioethics for clinicians: 20. Chinese bioethics. AB - Chinese Canadians form one of the largest groups in the Canadian cultural mosaic. Many of the assumptions implicit in a Western autonomy-based approach to bioethical deliberation may not be shared by Chinese Canadians. In traditional Chinese culture, greater social and moral meaning rests in the interdependence of family and community, which overrides self-determination. Consequently, many Chinese may vest in family members the right to receive and disclose information, to make decisions and to organize patient care. Furthermore, interactions between Chinese patients and health care workers may be affected by important differences in values and goals and in the perception of the nature and meaning of illness. Acknowledging and negotiating these differences can lead to considerable improvement in communication and in the quality of care. PMID- 11192659 TI - The medicine-literature connection moves online. PMID- 11192660 TI - A prediction. PMID- 11192661 TI - Pharmacist shortage. Prescription: power. PMID- 11192662 TI - Employee recruitment. Down to a science. PMID- 11192663 TI - HIPAA complications. Who's compliant? PMID- 11192664 TI - Gloria Jackson-Bacon. PMID- 11192665 TI - Flu inoculation. Speedy shots. PMID- 11192666 TI - Alternative medicine. CAM can do. PMID- 11192667 TI - Diagnostic imaging. Digital lifesaver. PMID- 11192668 TI - Electricity regulation. Power mad. PMID- 11192669 TI - Information technology. Keep up--or else. PMID- 11192670 TI - 1Q[3a] Do we need a nationwide physician licensure program? PMID- 11192671 TI - Easing doctor-nurse conflict. PMID- 11192672 TI - Trash sites. PMID- 11192673 TI - Norma Rae, R.N. PMID- 11192674 TI - When disaster strikes. Crises test leaders' nerve and range of skills. PMID- 11192675 TI - Pain management. Tools for implementing JCAHO's new standards. PMID- 11192676 TI - Going wireless. PMID- 11192678 TI - No better time. PMID- 11192677 TI - Wireless & handheld resource guide. PMID- 11192679 TI - Managed care, it's your move. PMID- 11192680 TI - Long live the public-sector carve-out! PMID- 11192681 TI - It's time to get ready for HIPAA. PMID- 11192682 TI - Don't 'treat' people; support them! PMID- 11192683 TI - Criminal-justice needs foster provider innovation. PMID- 11192684 TI - Better treatment from the bench. PMID- 11192685 TI - DTAP (Drug Treatment Alternative to Prison) offers model for helping offenders. PMID- 11192687 TI - The Gold Book buyer's guide. Company section. PMID- 11192686 TI - Is it time to switch methods? PMID- 11192688 TI - The Gold Book buyer's guide. Toll-free & fax numbers. PMID- 11192689 TI - The Gold Book buyer's guide. Product section. PMID- 11192690 TI - Key changes in state EMS offices. PMID- 11192691 TI - State & province survey. PMID- 11192692 TI - Government agencies. PMID- 11192693 TI - EMS organizations. PMID- 11192694 TI - Reactivity of Cd7-metallothionein with Cu(II) ions: evidence for a cooperative formation of Cd3,Cu(I)5-metallothionein. AB - Reaction of Cd7-metallothionein-2 (MT) with Cu(II) ions has been studied by a variety of spectroscopic techniques including UV-absorption, circular dichroism (CD) and luminescence spectroscopy. The addition of up to 5 Cu(II) equivalents to Cd7-MT resulted in a cooperative formation of the monomeric Cd3,Cu5-MT form, as revealed by the analytical data and the presence of isosbestic or isodichroic points in the respective UV and CD spectra. The presence of Cu(I) luminescence and the absence of Cu(II) EPR signal indicated that copper is bound in the Cu(I) oxidation state, i.e., Cd3,Cu(I)5-MT. Consequently, the reduction of Cu(II) ions is accompanied by the oxidation of thiolate ligands of the protein. The absorption features and the luminescence data at 77 K are consistent with the presence of an air-stable Cu(I)-cluster in Cd3,Cu(I)5-MT. The participation of other ligands, besides cysteine thiolates, in metal coordination cannot be ruled out. With more than 5 Cu(II) equivalents added a mixture of unstable MT metalloforms were formed. The concomitant reduction and binding of copper ions by metallated MT represent a new aspect of the MT structure. PMID- 11192695 TI - The DNA-bound orientation of Cu(II)-Xaa-Gly-His metallopeptides. AB - The DNA-bound orientations of Cu(II) x Xaa-Gly-L-His metallopeptides (where Xaa is Gly, L-Lys or L-Arg) were investigated by DNA fiber EPR spectroscopy and molecular modeling. Observed and calculated EPR spectra indicated that the g// axes of 1:1 Cu(II) complexes of the tripeptides tilted about 50 degrees from the DNA fiber axis. These results suggest that the complexes are stereospecifically oriented in the DNA minor groove. Although the side chain of the N-terminal amino acid residue did not affect the orientation of the DNA-bound complexes, it contributed to their stability in the presence of DNA; the Cu(II) complex of Gly Gly-L-His was found to dissociate to hydrated Cu(II) ion more extensively than the respective L-Lys-Gly-L-His and L-Arg-Gly-L-His complexes. The ionic interaction between the positively charged lysine or arginine residues and the negatively charged DNA phosphodiester backbone may result in the reduced dissociation of these complexes when bound to the DNA minor groove. PMID- 11192696 TI - Complexation of the antihypertensive drug oxprenolol with copper(II). AB - The complexation between copper(II) and the antihypertensive drug oxprenolol (HOxp) was studied both in methanol and slightly alkaline aqueous media at Cu:HOxp molar ratio from 1:1 to 1:10. Copper(lI) forms two types of complexes-a mononuclear violet one, CuOxp2, with bidentately bound ligands and a green dimeric one, Cu2Oxp2Cl2, in which the two Cu(II) centres are linked by the ligand through oxygen bridges. The crystal structure of the Cu2Oxp2Cl2 complex consists of two crystallographically non-equivalent centrosymmetric copper dimers. Each copper atom is four-coordinated in a distorted square-planar environment. The Cu2O2 structural core is characterized by a Cu1-O1-Cu1' angle of 104.15(13)degrees (Cu2-O2-Cu2' 104.30(13) degrees) and a relatively short Cu1 Cu1' separation of 3.026(1) A (Cu2-Cu2'-3.023(1) A). Magnetic susceptibility and EPR measurements indicate an antiferromagnetic coupling of the copper(II) centers. PMID- 11192697 TI - Platinum(II) and palladium(II) complexes with dithiocarbamates and amines: synthesis, characterization and cell assay. AB - The [M(ESDT)Cl]n (M = Pd or Pt; ESDT = EtO2CCH2(CH3)NCS2, methylamino-acetic acid ethyl ester-dithiocarboxylate) species have been reacted with various amines (py, pyridine; PrNH2, n-propylamine; c-BuNH2, cyclobutylamine; en, ethylenediamine) in dichloromethane or chloroform with the aim to obtain mixed ligand complexes. The neutral complexes [M(ESDT)(L)Cl] (L = py, PrNH2 or c-BuNH2) and the ionic species ([M(ESDT)(L)2]Cl and [M(ESDT)(En)]Cl) have been isolated, and characterized by IR and proton NMR spectroscopies. The crystal structure of [Pd(ESDT)(PrNH2)Cl] has been determined by X-ray crystallography. The behaviour of the complexes in various solvents was described on the basis of the proton NMR spectra. The complexes and the dithiocarbamato intermediates have been tested for in vitro cytostatic activity against human leukemic HL-60 and HeLa cells. PMID- 11192698 TI - Synthesis, characterization, antioxidative and antitumor activities of solid quercetin rare earth(III) complexes. AB - Eight rare earth metal(II) complexes with quercetin ML3 x 6H2O [L=quercetin (3-OH group deprotonated); M = La, Nd, Eu, Gd, Tb, Dy, Tm and Y] have been synthesized and characterized by elemental analysis, complexometric titration, thermal analysis, conductivity, IR, UV, 1HNMR and fluorescence spectra techniques as well as cyclic voltammetry. The quercetin:metal stoichiometry and the equilibrium stability constant for metal binding to quercetin have been determined. The antioxidative and antitumor activities of quercetin x 2H2O and the complexes were tested by both the MTT and SRB methods. The results show that the suppression ratio of the complexes against the tested tumour cells are superior to quercetin x 2H2O. The property of LaL3 x 6H2O reacting with calf thymus DNA was studied by fluorescence methods. The La-complex binding to DNA has been determined by fluorescence titration in 0.05 M Tris-HCl, 0.5 M NaCl buffer (pH 7.0). The results indicate that the interaction of the complex with DNA is very evident. PMID- 11192699 TI - DNA-binding and photocleavage studies of cobalt(III) polypyridyl complexes:. AB - Two complexes of [Co(phen)2IP]3+ (IP=imidazo[4,5-f][l,10]phenanthroline) and [Co(phen)2PIP]3+ (PIP=2-phenylimidazo[4,5-f][1,10]phenanthroline) have been synthesized and characterized by UV/VIS, IR, EA and mass spectra. The binding of the two complexes with calf thymus DNA has been investigated by absorption spectroscopy, cyclic voltammetry, viscosity measurements and DNA cleavage assay. The spectroscopic studies together with cyclic voltammetry and viscosity experiments support that both of the complexes bind to CT DNA by intercalation via IP or PIP into the base pairs of DNA. [Co(phen)2PIP]3+ binds more avidly to CT DNA than [Co(phen)2IP]3+, which is consistent with the extended planar and pi system of PIP. Noticeably, the two complexes have been found to be efficient photosensitisers for strand scissions in plasmid DNA. PMID- 11192700 TI - Metal-ion speciation in blood plasma incorporating the tetraphosphonate, N,N dimethylenephosphonate-1-hydroxy-4-aminopropilydenediphosphonate (APDDMP), in therapeutic radiopharmaceuticals. AB - In a quest for more effective radiopharmaceuticals for pain palliation of metastatic bone cancer, this paper relates results obtained with 166Ho and 153Sm complexed to the bone seeking phosphonate, N,N-dimethylenephosphonate-1-hydroxy-4 aminopropylidenediphosphonate (APDDMP). APDDMP is synthesised from the known bone cancer pain palliation agent 1-hydroxy-3-aminopropylidenediphosphonate (APD) and was complexed to lanthanide trivalent metal ions. This work is performed to utilise the idea that the energetic beta-particle emitter, 166 Ho, coupled with phosphonate ligands such as APD and APDDMP could afford a highly effective radiopharmaceutical in the treatment of bone cancer. Complex-formation constants of APDDMP with the important blood plasma metal-ions, Ca2+, Mg2+, and Zn2+ and the trivalent lanthanides Ho3+ and Sm3+ were measured by glass electrode potentiometry at 37 degrees C and I = 150 mM. Blood plasma models were constructed using the computer code ECCLES and the results compared with those gathered from animal tests. The 166Ho-APDDMP complex was found to have little liver or bone uptake while 153Sm-APDDMP had a moderate bone uptake. This was primarily due to the high affinity of APDDMP for Ca(II). Clinical observations could be explained by the blood plasma modelling. PMID- 11192701 TI - Comparison of three fungal laccases from Rigidoporus lignosus and Pleurotus ostreatus: correlation between conformation changes and catalytic activity. AB - The conformation changes in solution of three fungal laccases in different environmental conditions were examined by circular dichroism (CD) and electron paramagnetic resonance (EPR) spectroscopy. CD measurements indicate that the secondary structure of proteins depends slightly on the pH or ionic strength, though the presence of salt could interfere in the molecular recognition process between substrates and enzymes. The enzymes, however, are highly destabilized by prolonged exposure to low pH or high temperature. The observed unfolding of the proteins coincides with their inactivation and, in some cases, with precipitation. On the other hand, these conditions do not determine the disruption of the geometric arrangement of their metal centres, and this fact suggests that these centres represent the more stable core of the proteins. PMID- 11192702 TI - Copper(II) complexes with phenoxyalkanoic acids and nitrogen donor heterocyclic ligands: structure and bioactivity. AB - The copper complexes with the phenoxyalkanoic acids MCPA, 2,4-D, 2,4,5-T and 2,4 DP in the presence of a nitrogen donor heterocyclic ligand, phen or bipyam, were prepared and characterized. Interaction of Cu(II) with phenoxyalkanoic acids and bipyam leads to dinuclear or uninuclear neutral complexes while in the presence of phen uninuclear neutral or cationic forms have been isolated. The crystal structure of bis(1,10-phenanthroline)(2-methyl-4-chloro-phenoxyacetato)copper(ll) chloride-methanol(1/1)-water(1/0.6), 1 has been determined and refined by least squares methods using three-dimensional MoK, data. 1 crystallizes in space group P1, in a cell of dimensions a = 14.577(6)A, b = 1 1.665(5) A, c = 12.249(6) A, alpha = 98.38( 1)degrees, beta = 112.18( 1) degrees, gamma = 104.56(1 ) degrees, V= 1,798( 1) A3 and Z= 2. The cyclic voltammograms of uninuclear cationic complexes in dmf exhibit an extra cathodic wave due to the chloride ion. The available evidence supports an increasing antimicrobial effeciency for the cationic complexes. PMID- 11192703 TI - Whole-body scintigraphy in melanoma patients: comparison of 99Tcm-tetrofosmin and 201Tl. AB - The aim of this study was to determine the diagnostic value of 99Tcm-tetrofosmin whole-body imaging in comparison to 201Tl scintigraphy in patients with metastatic melanoma. In 27 patients with known or suspected melanoma metastases we performed 201Tl scintigraphy and 99Tcm-tetrofosmin scintigraphy using a 1-day protocol. In five patients with known locoregional metastasis the in vivo uptake kinetics of both radiotracers were compared. The final diagnosis was confirmed by surgical histology in 39 lesions (group I) and computed tomography (CT) and clinical course in 14 lesions (group II). In group I, containing mainly locoregional metastases, 201Tl scintigraphy correctly identified 36 of 39 metastases and 99Tcm-tetrofosmin 35 of 39 resulting in a sensitivity of 92% and 90% respectively. The T/B ratios of 201Tl (1.4-4.0, mean 2.15) were statistically significantly higher in comparison to tetrofosmin (1.3-3.0, mean 1.88). However, both radiotracers showed similar uptake and washout kinetics with a maximum of tracer uptake between 1 and 5 min p.i. In group II, containing mainly cerebral and pulmonary metastases, both methods correctly identified six of 14 metastases resulting in a sensitivity of only 43%. We conclude that the uptake of 99Tcm tetrofosmin and 201Tl in melanoma metastases is very similar. The T/B ratios with 99Tcm-tetrofosmin are significantly lower than with 201Tl. In locoregional melanoma metastases the sensitivity of tetrofosmin scintigraphy is identical with 201Tl imaging and amounts to 90%. In cerebral and lung metastases the sensitivity of both methods is limited when using whole-body scintigraphy. PMID- 11192704 TI - Factors influencing the accuracy of renal output efficiency. AB - Output efficiency (OE) has been proposed as an objective tool for the estimation of renal emptying. The aim of this paper was to evaluate some factors that may affect the value of this parameter obtained by a 99Tcm MAG3 renogram. In 22 patients, the effect of different types of renal background correction was calculated. In 10 patients, simultaneous gamma camera renography and multiple blood sampling allowed the error of using a heart curve instead of a plasma curve to be evaluated. Finally, an evaluation was carried out on the effect of neglecting the change of plasma activity between the end of the furosemide acquisition and the post-micturition view obtained after repositioning of the patient on the gamma camera: 142 patients who had had multiple blood sampling were retrospectively selected for that purpose. It has been shown that all these factors may significantly affect the value of OE, particularly in cases with poor renal drainage. Unless standardization of the procedure is introduced for some of these factors, the cut-off levels for good, fair and poor drainage may vary between centres. PMID- 11192705 TI - Dobutamine combined with low-level exercise for myocardial perfusion scintigraphy. AB - Increased abdominal background activity is one of the limitations of dobutamine myocardial perfusion scintigraphy which may interfere with interpretation of the images. In this study, we evaluated the value of low-level exercise supplementation to dobutamine infusion in improving image quality. The control group (n = 32, Group A) received dobutamine alone, while the study group received dobutamine plus low-level exercise for the last 2 min of dobutamine administration (n = 26, Group B). One hundred and eleven MBq of 201Tl was injected 1 min before cessation of peak dose. The ratios of cardiac/hepatic (C/HEP), cardiac/subdiaphragmatic (C/INF) and cardiac/pulmonary (C/PUL) were calculated from anterior planar images taken immediately following the test. Cardiac/non-cardiac activity was also visually graded on a three-point scale. Visual evaluation showed improved cardiac/non-cardiac ratios as confirmed by significantly higher C/HEP and C/INF ratios for Group B (1.5+/-0.3 and 1.7+/-0.2, respectively) compared to corresponding values in Group A (1.2+/-0.4 and 1.4+/ 0.4, respectively) (P<0.05). The cardiac/pulmonary (C/PUL) ratio was also higher for Group B (2.3+/-0.5) as compared to corresponding value in Group A (2.0+/-0.6, respectively), but this difference did not reach statistical significance (P > 0.05). No difference in the frequency of side effects and ECG changes were detected between the two groups (P > 0.05). Low-level exercise supplementation to dobutamine infusion for myocardial perfusion scintigraphy is a safe method and leads to a significant decrease in uptake by the areas adjacent to the heart, improving image quality. PMID- 11192706 TI - Impact of radionuclide ventriculography prior to elective abdominal aortic reconstruction. AB - We evaluated how preoperative radionuclide ventriculography (RNV) influences the clinical management of 96 patients referred for elective infrarenal abdominal aortic surgery. Of these, 11 had aortoiliac occlusive disease and 85 an abdominal aortic aneurysm. In 89 patients (93%), there was a known history or clinical evidence of coronary artery disease prior to RNV. The scan was abnormal in half the patients. There were 56 patients with left ventricular ejection fraction (LVEF) > 50% and 40 with LVEF < or = 50%. The LVEF ranged between 10% and 88% with a mean of 52.8+/-14.1%. There was normal wall motion in 56 patients and wall abnormalities were present in 40, including four LV aneurysms. After initial assessment, 19 patients did not proceed to surgery for a variety of reasons. Cardiology consultation was requested in 11 patients, six of which were delayed or turned down for surgery mainly on cardiac grounds. Only one of these underwent cardiac catheterization. Of the remaining 77 patients who underwent surgery, 15 were seen by a cardiologist and one was delayed in order to optimize his cardiac status. No patient underwent prophylactic coronary angioplasty/stenting or revascularization preoperatively. In addition, based on the RNV results and in conjunction with the clinical findings, six patients had pulmonary artery catheters inserted either the night prior to operation (n = 3) or after induction to anaesthesia (n = 3). This is the largest reported British series of cardiac testing using RNV prior to abdominal aortic surgery. Coronaryartery disease is very common amongst such patients. RNV influences our decision-making and patientselection. An abnormal result may alter the clinical management, lead to a cardiology referral (26/96, 27% in this series) and have anaesthetic implications. PMID- 11192707 TI - The role of rhinoscintigraphy in the evaluation of nasal mucociliary clearance function in patients with sinusitis. AB - Nasal mucociliary clearance is one of the homeostatic systems of the respiratory mucosa. Various rhinopathic conditions may involve alterations in nasal mucociliary clearance. The aim of this study was to assess the clinical role of rhinoscintigraphy in the evaluation of nasal mucociliary clearance function of sinusitis patients in comparison with a healthy control group. A single droplet of 99Tcm-labelled macroaggregated albumin (99Tcm-MAA) was deposited on the floor of the nasal meatus about 1 cm behind the mucocutaneous junction, and its course was followed with a gamma camera. The nasal mucociliary clearance was presented as the velocity (mm x min(-1)) of nasal mucociliary transport of the 99Tcm-MAA droplet. A significant difference in nasal mucociliary clearance was observed between the two groups, with a mean of 4.28+/-1.38 mm x min(-1) (4.3+/-1.35 mm x min(-1) in the right nostril, 4.27+/-1.42 mm x min(-1) in the left nostril) for the controls; and 1.8+/-0.64 mm x min(-1) (1.79+/-0.65 mm x min(-1) in the right nostril, 1.82+/-0.63 mm x min(-1) in the left nostril) for the patients with sinusitis. Rhinoscintigraphy is a safe, easy, quick and reliable imaging method for evaluating the ciliary activity of nasal mucosa and the nasal mucociliary clearance function in patients with sinusitis. PMID- 11192708 TI - Does bowel preparation improve the quality of abdominal gallium scintigraphy? AB - Physiological accumulation of gallium in the intestine is a major weakness of gallium scintigraphy in evaluating the abdomen. In this study, we used two different cathartics to evaluate the efficacy of bowel cleansing in improving the quality of abdominal gallium imaging. One hundred and fifty patients underwent gallium scintigraphy and were randomly divided into three groups. Group A received no bowel preparation, Group B received 30 ml of castor oil the night before imaging, and Group C received bisacodyl the night before imaging. Gallium activity in the intestine was rated on a three-point scale from 0 to II based on the anterior view of a delayed 48-h gallium image. Our data showed that the incidence of gallium accumulation in the small intestine was low. On the contrary, there was high prevalence of gallium activity in the colon. Forty-eight percent of Group A patients had obvious gallium activity in the colon. The percentage decreased significantly to 28% and 22% in Groups B and C, respectively. No significant difference was noted between Group B and Group C. In conclusion, our data suggest that the application of either castor oil or bisacodyl significantly improves the quality of 48-h abdominal gallium scintigraphy. There were no significant differences in the efficacy of bowel cleansing on gallium activity between these two laxatives. PMID- 11192709 TI - A simplified method for processing dynamic images of gastric antrum. AB - By means of a dynamic acquisition protocol and a Fourier transform algorithm the scintigraphic technique can be used to assess gastric antral motility. In previous approaches, however, the definition of a region of interest (ROI) that gives rise to an unequivocal result of the analysis of the corresponding time activity curve might be crucial. To overcome this problem we evaluated a new technique based on a fixed box-ROI and a simple weighting principle. Eight healthy volunteers ingested a meal that contained a 99Tcm-stannous colloid labelled omelette. Gastric emptying was assessed from static images taken at 30 mm intervals for 2 h. Anterior dynamic frames of 1 s each, which were acquired for 5 mm after each static acquisition, were used to determine the frequency of antral contractions. In order to allow for precise outlining of the antrum, each set of dynamic images was at first reframed into a single 5-mm image. The same ROI (20 pixels vertical, 15 pixels horizontal) was then positioned over the distal portion of the antrum on each reframed image. On each 1-s frame the obtained counts in each of the 15 columns of 20 pixels were summed. Then the localization of the geometric centre of radioactivity in the 15 columns was determined. On the assumption that the horizontal oscillations of the geometric centre of radioactivity in the ROI reflected the contractile activity of the antrum, the frequency of these contractions was calculated by fast Fourier transform analysis of the obtained time versus geometric centre curve. In all subjects, our technique gave unequivocal frequencies of antral contractions at each time point. Statistical analysis did not reveal any intraindividual variation in this frequency during gastric emptying. We believe that the simplified scintigraphic method is an advantageous alternative for assessing the frequency of antral contractions. PMID- 11192710 TI - A 99Tcm-labelled leukotriene B4 receptor antagonist for scintigraphic detection of infection in rabbits. AB - In a search for a rapid and accurate imaging agent for scintigraphic detection of infection and inflammation, an LTB4 receptor antagonist, 99Tcm-RP517, which contains the hydrazino nicotinamide moiety, has been developed recently. To study the in vivo behaviour of 99Tcm-RP517, rabbits with Escherichia coli infection were injected intravenously with 99Tcm-RP517. Gamma camera images were obtained and ex vivo bio-distribution was determined at several hours post-injection (p.i.). In a separate set of rabbits the choledochal duct was cannulated to quantitatively monitor the hepatobiliary clearance of the radiopharmaceutical. The receptor binding fraction of the radiolabelled RP517 exceeded 70%. Accumulation of 99Tcm-RP517 in the abscess was visualized as early as 1 h p.i. Due to rapid blood clearance (t1/2 alpha=18+/-0.6 min, t1/2 beta=6.5+/-0.4 h) and high abscess uptake, the abscess-to-muscle ratios increased with time from 7.0+/ 2.3 at 1 h p.i. to 44.3+/-4.6 at 20 h p.i. The agent mainly cleared via the hepatobiliary route: 50% of the radiolabel was recovered in the small bowel at 1 h p.i., whereas 85% was found in cecum and sigmoid at 20 h p.i. In conclusion, 99Tcm-RP517 rapidly visualized E. coli abscesses in rabbits. The agent rapidly cleared from the blood, mainly via the hepatobiliary route. High abscess-to background ratios were achieved. The accumulation in the intestines could limit the applicability of this agent for detecting infectious processes in the abdominal area. The development of a more hydrophilic analogue of 99Tcm-RP517 could improve the clinical applicability of this agent. PMID- 11192711 TI - Effect of E5510, a novel antiplatelet agent, on platelet deposition in atherothrombotic lesions: evaluation by 111In platelet scintigraphy. AB - We evaluated the short-term effects of a novel antiplatelet agent, 4-cyano-5,5 bis(methoxyphenyl)-4-pentenoic acid (E5510), using 111In platelet scintigraphy (PSG) and B-mode ultrasonography (US). Fifteen patients with platelet deposition at either the carotid bifurcation or abdominal aorta on PSG were randomized into two groups: seven were followed without anti-thrombotic medication (Group A) and eight received E5510 (4 mg x day(-1)) (Group B). After 8 weeks, PSG and US were repeated in all patients. Platelet deposition was assessed visually and semi quantitatively using a platelet accumulation index. Visual analysis showed that seven out of eight patients became negative for platelet deposition after treatment in Group B, while none changed in Group A. The platelet accumulation index of vessels with platelet deposition was significantly reduced after treatment in Group B (12.4+/-3.9% vs 6.0+/-7.1%, p <0.01), while there was no significant change in the vessels without platelet deposition (2.9+/-3.0% vs 2.9+/-4.1%). In Group A, none of the vessels showed any change (8.1+/-6.4% vs 8.9+/-7.3%). However, there was no significant reduction of carotid plaque size in either group. Short-term E5510 therapy inhibited platelet deposition in active atherothrombotic lesions, and the combination of PSG and US was useful for evaluating the effectiveness of anti-thrombotic drugs in vivo. PMID- 11192712 TI - The effect of protein or energy restriction on the biodistribution of Na99TcmO4 in Wistar rats. AB - The effect of malnutrition on the biodistribution of radiopharmaceuticals is not known. We studied the biodistribution of 99Tcm-labelled sodium pertechnetate (Na99TcmO4) in two rat models of malnutrition. Three groups of 2-month-old rats were separated according to their diets: (1) control diet, 23% protein (C); (2) protein-restricted, receiving 8% protein (PR), both ad libitum; and (3) energy restricted, receiving 60% of control diet (ER). After 21 days of the diet, 99Tcm was injected and the animals were killed after 30 min. The organs were isolated, their weight determined and the absolute per cent (%ID) and the per cent per gram injected dose (%ID x g(-1)) calculated. The %ID and %ID x g(-1) had a similar pattern, increasing in stomach and brain and decreasing in the thyroid, but did not change significantly in kidney, lung, liver, bone or testis in PR rats, except in the heart where the increase was only observed in the %ID x g(-1). In the ER group the %ID x g(-1) was decreased in the bone only, and did not change in the other organs. It is suggested that when using Na99TcmO4 scintigraphy in malnourished patients, the different patterns of distribution must be kept in mind. PMID- 11192713 TI - A receptor-specific peptide for imaging infection and inflammation. AB - The chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMLP), when radiolabelled, continues to be an attractive agent for imaging infection or inflammation. Previously, several analogues of fMLP have been prepared and radiolabelled using a bifunctional chelating agent conjugation procedure that was relatively long and complex. We have prepared a new analogue of fMLP, TP765, by the addition of 4-aminobutyric acid (4-ABA) and a group of four amino acids, Gly Gly-d-Ala-Gly, to the carboxy terminus (i.e. to the phenylalanine) of fMLP. The adduct -(4-ABA)-Gly-Gly-d-Ala-Gly- serves as a chelating moiety for strong chelation with 99Tcm. The use of a peptide as a chelating moiety greatly simplified the synthetic procedure and rendered the analogue ready for instant chelation with 99Tcm. HPLC analysis revealed that 99Tcm-TP765 was a single chemical entity that retained biological activity and neutrophil specificity. 99Tcm-TP765 was stable when challenged with strong chelating agents in vitro and had rapid but biphasic blood clearance (alphat1/2 = 7 min, betat1/2 = 45 min). Approximately 90% of the radioactivity had cleared from circulation within 45 min post-injection and the agent had accumulated in experimental bacterial or sterile abscesses in significantly (P<0.05) higher quantities than the analogues evaluated previously. Generally, the biodistribution pattern of 99Tcm-TP765 was similar to that of other analogues examined and its abscess uptake was independent of the abscess age. In conclusion, a new analogue of fMLP, 99Tcm TP765, was prepared by a simple procedure. This new analogue has properties similar to those of previously examined analogues used as agents for imaging infection or inflammation. PMID- 11192714 TI - Clinical outcome after standardized versus dosimetric radioiodine treatment of hyperthyroidism: an equivalence study. AB - The aim of this study was to investigate the equivalence in outcome of standardized versus uptake-adjusted dosing of radioactive iodine (131I) for hyperthyroidism. We performed a 1-year follow-up study of two patient cohorts: 326 patients referred for 131I treatment of hyperthyroidism in Graves' disease (GD; n=216) or toxic multinodular goitre (TMG; n=110) in the period June 1995 to January 1998. Of these patients 128 were treated according to a standardized regimen, based on palpated thyroid volume and diagnosis, and 198 with a 131I uptake-adjusted dosimetric method. The incidence of hypothyroidism, euthyroidism or recurrence of disease was recorded. In Graves' disease hypothyroid outcome in the standardized versus adjusted method was 40.7% vs 44.6% (95% CI difference, 17.4 to +9.5%); it was 67.4% vs 70.8% (95% CI difference -15.9 to +9.3%) for all non-euthyroid outcomes. In TMG, due to wide confidence interval ranges a conclusion of equivalence could be made only for recurrence of hyperthyroidism (mean -3.2%, 95% CI, -13.8 to +7.5%). A simplified dosage method for 131I treatment of hyperthyroidism, which omits 131I uptake adjustment, may improve procedure efficiency and patient convenience, and leads to an equivalent outcome in GD and probable equivalent outcome in TMG. PMID- 11192715 TI - Use of the rat pancreatic CA20948 cell line for the comparison of radiolabelled peptides for receptor-targeted scintigraphy and radionuclide therapy. AB - We have evaluated the usefulness of the rat pancreatic CA20948 tumour as an in vitro cell culture model and as an in vivo model in Lewis rats comparing different radiolabelled peptides for receptor-targeted scintigraphy. In vitro the receptor-specific uptake and internalization of different radiolabelled analogues of somatostatin, bombesin, substance P and cholecystokinin were demonstrated. Analogues were selected based on high-affinity binding to their respective receptors. Their uptake and internalization in CA20948 cells were compared to these processes in AR42J cells, a well-known rat pancreatic tumour cell line used for peptide-receptor studies. Receptor-specific internalization, which was blocked by excess unlabelled peptide analogue, was found in both the CA20948 and AR42J cells for all the peptide analogues tested. This indicates specific receptor expression for all the different peptides, making these cells highly suitable for peptide studies. Internalization of the different peptides was as follows, in increasing order: [111In-DOTA0]CCK < [111In-DTPA0,Arg1]substance P < [111In-DTPA0]octreotide < [111In-DTPA0,Pro1,Tyr4]bombesin. Internalization appeared to be time and temperature dependent. In accordance with the in vitro experiments, receptor-specific uptake of all the peptide analogues was also found in vivo in the solid CA20948 tumour. The in vivo tumour uptake of [111n DTPA0]octreotide was the highest amongst the peptides tested, the order of tumour uptake being [111In-DTPA0]octreotide >[111In-DTPA0,Pro1,Tyr4]bombesin >[111In DTPA0,Arg1]substance P > [111In-DOTA0]CCK, which is different from the in vitro findings and points to either different receptor numbers on the tumour cells for the different peptide receptors in vitro and in vivo or to differences between the peptides with regard to metabolic stability. It can be concluded that the CA20948 tumour, both in cell culture and as a solid tumour in rats, is a very useful model for peptide receptor scintigraphy and radionuclide therapy studies. PMID- 11192716 TI - Labelling efficiency of ten radiopharmaceuticals. PMID- 11192717 TI - Nuclear nephrourology, no more the cinderella of nuclear medicine. PMID- 11192718 TI - Follow-up of differentiated thyroid cancer: comparison of multiple diagnostic tests. AB - The radioablation of thyroid remnants improves the prognosis of differentiated thyroid cancer. In our prospective study an activity of 3.7 GBq 131I failed to completely ablate the remnants in 46 out of 101 patients, but a 3-year follow-up period was uneventful. One other patient had a recurrence early after thyroidectomy. In view of possible stunning effects of 131I it might be advantageous to visualize such remnants by imaging modalities which do not emit beta-particles. Our data have revealed that neither magnetic resonance imaging (MRI), nor ultrasonography (US), nor 99Tcm-sestamibi scintigraphy, nor positron emission tomography could detect or reliably exclude minimal remnants. Such remnants did not produce thyroglobulin (Tg). A 123I and 131I uptake of> 10% after thyroidectomy was associated with about a 90% probability of persistent remnants. On the other hand, MRI was helpful in the patient group (n = 32) with Tg>4ng x ml(-1) at the second whole-body scintigraphy (TSH>30 mU x l(-1)) for planning the management of lymph node metastases (n = 15 patients): 12 patients had subsequent surgery and three patients radioiodine therapy. We recommend that MRI be used early in follow-up care when Tg is elevated. The decision of whether or not to treat persistent thyroid remnants should not be made on the basis of MRI, US or nonspecific scintigraphic methods. Complete ablation did not appear to have any clinical benefit in our study group. PMID- 11192719 TI - Electron transfer in natural proteins theory and design. PMID- 11192720 TI - Methylamine dehydrogenase. Structure and function of electron transfer complexes. PMID- 11192721 TI - Trimethylamine dehydrogenase and electron transferring flavoprotein. PMID- 11192722 TI - Amine oxidases and galactose oxidase. PMID- 11192723 TI - Electron transfer and radical forming reactions of methane monooxygenase. PMID- 11192724 TI - Flavocytochrome b2. PMID- 11192725 TI - Flavin electron transfer proteins. PMID- 11192726 TI - Flavocytochrome P450 BM3 substrate selectivity and electron transfer in a model cytochrome P450. PMID- 11192727 TI - Peroxidase-catalyzed oxidation of ascorbate. Structural, spectroscopic and mechanistic correlations in ascorbate peroxidase. AB - Ascorbate-dependent peroxidase activity was first reported in 1979 (Groden and Beck, 1979; Kelly and Latzko, 1979) and ascorbate peroxidase (APX) is, therefore, a relative newcomer to the peroxidase field--horseradish (HRP) and cytochrome c (CcP) peroxidases were, for example, first identified in 1903 (Bach and Chodat, 1903) and 1940 (Altschul et al., 1940) respectively. The APX area was reviewed by Dalton in 1991 (Dalton, 1991): at that time, there was very little detailed kinetic, spectroscopic or functional information available and no structural information had been published. Since 1991, there have been some major advances in the field, most notably with the publication, in 1995, of the first crystal structure for an APX enzyme (Patterson and Poulos, 1995). This information, together with the availability of new recombinant expression systems (Yoshimura et al., 1998; Caldwell et al., 1998; Dalton et al., 1996; Patterson and Poulos, 1994), served as a catalyst for the publication of new functional and spectroscopic data and has meant these data could be sensibly rationalized at the molecular level. The aim of this review is to summarize the more recent advances in the APX area and, as far as possible, to draw comparisons with other, more well-characterized peroxidases. The review will concentrate on the ways in which structural, spectroscopic and mechanistic information have been used in a complementary way to provide a more detailed picture of APX catalysis. The more biological and physiological aspects of APX enzymes have been previously covered in a comprehensive manner (Dalton, 1991) and will not, therefore, be dealt with in detail here. PMID- 11192728 TI - Adenosylcobalamin-dependent enzymes. PMID- 11192729 TI - Ribonucleotide reductase. A virtual playground for electron transfer reactions. PMID- 11192730 TI - Molybdenum enzymes. PMID- 11192731 TI - Nickel containing CO dehydrogenases and hydrogenases. AB - The two redox catalysts described here can generate very low potential electrons in one direction and perform chemically difficult reductions in the other. The chemical transformations occur at unusual metal clusters. Spectroscopic, crystallographic, and kinetic analyses are converging on answers to how the metals in these clusters are arranged and how they are involved in the chemical and redox steps. The first structure of CO dehydrogenase, which will appear in the next year, will help define a firm chemical basis for future mechanistic studies. In the immediate future, we hope to learn whether the hydride intermediate in hydrogenase or the carbonyl intermediate in CO dehydrogenase bind to the Ni or Fe subsites in these heterometallic clusters. Or perhaps could they be bridged to two metals? Inter- and intramolecular wires have been proposed that connect the catalytic redox machine to proximal redox centers leading eventually to the ultimate redox partners. Elucidating the pathways of electron flow is a priority for the future. There is evidence for molecular channels delivering substrates to the active sites of these enzymes. In the next few years, these channels will be better defined. The products of CO2 and proton reduction are passed to the active sites of other enzymes and, in the case of H2, even passed from one organism to another. In the future, the mechanism of gas transfer will be uncovered. General principles of how these redox reactions are catalyzed are becoming lucid as the reactions are modeled theoretically and experimentally. Proton and CO2 reduction and the generation of C-C bonds from simple precursors are important reactions in industry. H2 could be the clean fuel of the future. Hopefully, the knowledge gained from studies of hydrogenase, CO dehydrogenase, and acetyl-CoA synthase can be used to improve life on earth. PMID- 11192732 TI - Cytochrome cd1 nitrite reductase structure raises interesting mechanistic questions. PMID- 11192733 TI - Mitochondrial cytochrome bc1 complex. PMID- 11192734 TI - Bovine heart cytochrome c oxidase. PMID- 11192735 TI - Reaction centres of purple bacteria. AB - The bacterial reaction centre is undoubtedly one of the most heavily studied electron transfer proteins and, as this article has tried to describe, it has made some unique contributions to our understanding of biological electron transfer and coupled protonation reactions, and has provided fascinating information in areas that concern basic properties such as protein heterogeneity and protein dynamics. Despite intensive study, much remains to be learned about how this protein catalyses the conversion of solar energy into a form that can be used by the cell. In particular, the dynamic roles played by the protein are still poorly understood. The wide range of time-scales over which the reaction centre catalyses electron transfer, and the relative ease with which electron transfer can be triggered and monitored, will ensure that the reaction centre will continue to be used as a laboratory for testing ideas about the nature of biological electron transfer for many years to come. PMID- 11192736 TI - Methanol dehydrogenase, a PQQ-containing quinoprotein dehydrogenase. PMID- 11192737 TI - [Factors influencing liberation of drug from semisolid dosage forms]. AB - Liberation of salicylic acid--as a model active agent--was investigated from white petrolatum, creams w/o and o/w types and hydrogels. Active agent was applied in suspended, dissolved forms, in inclusion complexes and solubilized state. The process of liberation was studied by a continuous through-flow method, with Hanson vertical diffusion cell. The results of experiments were evaluated by factorial design method. Increase of the concentration of salicylic acid, polarity of vehicle and solubilized state of drug increased the drug release. It was established that the partitioning released drug was the most important step of drug release. Factors changing partitioning influenced the liberation to the highest degree. PMID- 11192738 TI - [In vitro study of emulsions containing methoxsalen]. AB - Vitiligo is an acute disease of skin with inflammation which means damage of melanocites, their defined partial paint lack. It is a frequent sickness which is very conspicuous and disturbing illness. For its treatment, systematically and topically psoralen-derivatives, UV-A radiation and other possibilities are used. Metoxsalen is one of them which is practically insoluble in water. Authors planned to increase the solubility of the pharmacon, and they studied with in vitro diffusion method, how the type of the emulsions influence the liberation and diffusion of metoxsalen. PMID- 11192739 TI - [Preparation of pellets with a centrifugal granulator]. AB - It has been investigated how the centrifugal-granulator is applicable to form paracetamol pellets with good mechanical, powder rheological and dissolutional properties. During the preparation process the mechanical parameters were the same only the percentage of the effective material was changed. The authors found that the centrifugal-granulator is well applicable to form good pellet particles which have good dissolution and mechanical parameters to from needle shaped raw materials. PMID- 11192740 TI - [Comparison of in vitro model examinaitons with respect to drug release from suppositories]. AB - 9 lipophilic suppository bases with different physical-chemical parameters were examined. Buspiron-hydrochloride, an anxiolytic drug with good water-solubility was used--partly as a model--as a pharmacon, in a concentration of 10.0 mg/2.00 g. The rate and extent of in vitro drug release was monitored with static and dynamic methods. Kidney-dialysing membranes with various surfaces were used. The quantitative measurements were carried out spectrophotometrically and the amount of the diffused drug was determined at lambda = 298 nm. The mean values were calculated from 5 parallel measurements each time. The percentage values of in vitro relative availability revealed that the results of the two static diffusion studies did not differ significantly (p < 0.05) and were almost independent of the size of the membrane surface. The results of the dynamic diffusion method were well-reproducible but were vehicle-dependent. The process of release was characterized by the mathematical transformation of the release curves, while the correlation coefficients described the closeness of the relation. Two German vehicles, namely Witepsol H 15 with a medium hydroxyl value and Massa Estarinum 299, and a French vehicle, Suppocire AS2X were found to be excellent for the formulation of suppositories containing Buspiron-hydrochloride. PMID- 11192741 TI - [Tin compounds in pharmacy and nutrition]. AB - The occurrence of tin in plants, animals and humans is discussed, in relation to its abundance in the lithosphere and hydrosphere and the range of the different tin(II) and tin(IV) complexes formed. A reasoned consideration of its essentiality for living species is provided. It is concluded that tin is beneficial, even if not yet proved to be an essential element. After reference to the chemistry of tin compounds, there is a detailed discussion of their toxicity in animals and humans. Feasible routes for tin intake and uptake into humans are described. The past and current use of tin pharmaceuticals is reviewed and the areas for which they are currently permitted for use in humans as dentifrices and mouth washes, as radio-pharmaceuticals and for the treatment of jaundiced newborns are described. A detailed review of tin-containing antitumour agents as representative tin pharmaceuticals is also given. Finally, a list of tin containing drugs and drug candidates is also shown. PMID- 11192742 TI - A nonlinear model for mammary gland growth and regression in lactating sows. AB - The objective was to propose an empirical mathematical model to describe mammary gland growth and regression in lactating sows. A nonlinear dynamic model based on the logistic function was constructed, and data from 61 sows were used to illustrate the model. Sows were fed four diets with two levels of energy and of protein during lactation, and individuals were slaughtered over a 30-d period to produce a cross sectional data set on weight and composition variables from suckled mammary glands. Data (y(x)) were obtained for each day of lactation (x) and fitted by nonlinear regression. The logistic distribution function was modified for different durations of growth (f; days/gram of weight or composition) and regression (g; days/gram of weight or composition): [formula in text] where y(max) is maximum weight or composition and x(max) is day of lactation at maximum. Based on results for wet weight, for example, individually suckled mammary glands grow until between Day 21 and 28 of lactation and reach a maximum of about 500 to 600 g, depending on diet. Growth pattern of mammary glands can be described well with an asymmetric nonlinear model, using different durations for growth and regression. From this model, it was possible to estimate directly biologically important parameters: maximum weight or composition, day of lactation at maximum weight or composition, and durations of growth and regression. This model can be applied to describe mammary gland growth patterns for other species and to describe similar growth or production patterns. PMID- 11192743 TI - Analysis of inheritance of growth trajectories in laboratory populations of guppy fish. AB - We analysed the variation of growth trajectories for body length from 40 to 90 days of age in three laboratory populations of Poecilia reticulata. The populations used were two lines of guppy-fish obtained by artificial selection for increased and decreased body length at 70 days and one line maintained under free-breeding condition. The factor analysis performed on the phenotypic correlation matrices among age-specific values of body length showed that a very large portion of the phenotypic variation is confined to a single factor. This factor corresponds to a simultaneous increase/decrease at all ages, hence representing the variation in the height of the growth trajectories. A smaller portion of the variation describes an increase/decrease at early ages followed by the reverse in the later ages, which corresponds to the variation in the shape of the trajectories. The genetic analysis performed on the height and shape of the growth curves showed a additive genetic component for the height in the free breeding population and for the shape in the selected lines. PMID- 11192744 TI - Relationships among biological growth parameters for body weight in Japanese children. AB - Longitudinal weight records for 360 boys and 345 girls from birth to young adulthood are used. The Count-Gompertz growth curve is fitted to individual growth records in order to characterize individual body weight growth. The authors present the mean-constant growth curves of boys and girls divided by weight at the peak weight velocity for boys and girls, and also girls are subdivided by their weight at menarche. Adult weight has no simple relationship with the timing of adolescence and menarcheal age. Adult weight is, nevertheless, negatively correlated with the timing of adolescence (or menarcheal age) when weight at the timing of adolescence (or menarcheal weight) and/or age at growth completion are held constant. Age at growth completion also negatively correlated with weight at menarche when adult weight and menarcheal age are held constant. Even if it is difficult to find a simple biological relationship among these parameters, for researchers looking for relationships and structures among biological parameters, this partial correlation may be useful. A contra-pair of biological parameters, age and weight, at two growth epochs of weight is introduced, and its properties are discussed in detail. PMID- 11192745 TI - Role of tirofiban in the medical treatment of the intermediate-risk patient with an acute coronary syndrome cannot be denied. PMID- 11192746 TI - Estimating the prevalence of aspirin use in the prevention of myocardial infarction. PMID- 11192747 TI - Low-dose dobutamine imagings predicting regional improvement in left ventricular function after revascularization. PMID- 11192748 TI - [Antioxidative properties of ascorbic acid]. AB - Vitamin C (ascorbic acid) is an important hydrophilic compound with antioxidative effect. In the introduction the authors describe possible consequences of loss of vitamin C synthetic ability in an evolutionary ancestor of Anthropoidea. Metabolism of this vitamin is described briefly along with possibilities of its supplementation and determination in biological fluids. Highest attention is paid to metabolic effects of vitamin C, respectively to changes which can be observed after its deprivation, or after the supplementation with this vitamin. Protective effect of vitamin C against lipoperoxidation, its role in modulation of immunity and tumorigenesis are described. Many effects of vitamin C can be explained by its antioxidative activity. The authors show that under concrete conditions, administration of vitamin C can be accompanied by a prooxidative effect. Since vitamin C works in cooperation with other antioxidants, its administration in diseases which are followed by oxidative stress is move effective when used in combined preparations. PMID- 11192749 TI - [Atypical eating disorders, a diagnostic and therapeutic problem? AB - Paper deals with problems of atypical forms of food intake disorder. Such disorders can be divided into three groups. First group included sub-clinical forms of food intake disorders. Patients with signs of thinning are included into the second group; however, their active role in slimming cannot be identified. In the third group the accompanying syndromes prevail, e.g. the syndrome of depression and obsessive-compulsive syndrome. Problems in the diagnostics and therapy of those atypical forms are discussed. PMID- 11192750 TI - [Resistance of hematologic neoplasm cells to cytostatics. Part II]. AB - Resistance to cytotoxic drugs is a serious drawback in the treatment of patients with tumours, both of the haemopoietic and non-haemopoietic origin. The cytotoxic effect of drugs on the malignant cells manifests as the process of apoptosis. In the resistant malignant cells, apoptosis becomes prevented by several mechanisms. The multidrug resistance (MDR) is one of the principal mechanisms when the cancer cells develop resistance to multiple chemically and functionally unrelated cytotoxic compounds. The decrease of the cytotoxic drug concentration at the molecular target site may come from activation of some efflux membrane systems participating in the transport of cytotoxic drugs out of the cell (e.g. Pgp, MDR, and LRP). Another mechanism of resistance is the increased enzymatic detoxification of the drug by glutathion-s-transferase system. Changes in the molecular target of the cytotoxic drug such as topoisomerase molecule can be also responsible for the resistance. At least two additional mechanisms of resistance of tumour cells were identified. Resistance can come from either deregulation of proapoptotic mechanisms in tumour cells or by increased activity of reparation processes which control the damaged molecule of DNA. Several methods that detect the cause of resistance in distinct cell populations have been developed. The great effort is now focused on both the detection of mechanisms of the resistance and on the clinical procedures of overcoming the resistance to cytotoxic drugs. PMID- 11192751 TI - [Molecular basis of hereditary antithrombin defects in 10 Czech families]. AB - BACKGROUND: Molecular basis of antithrombin deficiency has not yet been studied in Czech Republic. We looked for the causal mutations throughout the antithrombin gene in 26 patients from 10 unrelated families with antithrombin defect. METHODS AND RESULTS: We screened the gene by conformation sensitive gel electrophoresis and sequenced the mismatched regions using fluorescence technology to characterise mutations and polymorphisms. Mutations were detected in all ten families. Four novel mutations were identified in four families with type I antithrombin defect: Trp-6Arg, 5386-5387delCT, Glu163Stop, and 13246-13248del TGA causing deletion of Glu377 with change of Asn376 to Lys. In other three type I families we found following mutations: splicing site mutation G2777C, Arg197Stop and entire gene deletion. In the family carrying Trp-6Arg mutation antithrombin Vienna (Gln118Pro) was also detected. Leu99Phe recurrent in south-eastern Europe was identified in three families with type II defect. Only the homozygous carries of the mutation were symptomatic, although the heterozygous carries had decreased functional levels. CONCLUSIONS: Four novel mutations in families with type I antithrombin deficiency were characterised. In one family two different genetic defects were identified to be responsible for type I and II phenotypes. Altogether our data agree with the expected heterogeneity of the AT genetic defect. PMID- 11192752 TI - [Autoantibodies to GAD65, IA2 and insulin in Czech children with type 1 diabetes]. AB - BACKGROUND: Autoimmune insulitis leading to insulin dependent diabetes mellitus (IDDM, Type 1 Diabetes) is accompanied by autoantibodies as its invaluable markers. The aim of the study was to determine the frequency of autoantibodies against GAD65, IA2 and insulin in Czech diabetic children at the disease onset. METHODS AND RESULTS: Sera of 105 newly diagnosed children with IDDM drawn within 24 hours after the first insulin dose were investigated for anti-GAD65, anti-IA2 and insulin autoantibodies (IAA) using RIA methods. The cut-off normal levels were determined as the 99th percentile of 105 non-diabetic children. At given 99% specificity, the sensitivity was 71% for anti-GAD65, 73% for anti-IA2, and 46% for IAA. 29% diabetic children were positive for all three autoantibodies, 25% had anti-GAD65 and anti-IA2 (IAA negative), 5.7% anti-GAD65 and IAA (anti-IA2 negative), 7.6% anti-IA2 and IAA (anti-GAD65 negative). As the only positive autoantibody, anti-GAD65 was found in 12%, anti-IA2 in 11%, and IAA in 3.8% children. In 5.7% children, none of the investigated autoantibodies was positive. Diabetic children diagnosed before the age of 5 years had significantly higher prevalence of IAA than the older ones. CONCLUSIONS: We have determined normal levels in healthy children, and prevalence at childhood IDDM onset of autoantibodies against three main molecular-defined autoantigens. PMID- 11192753 TI - [Dynamic liver function study using the lidocaine test]. AB - Lidocaine clearance test may reflect the integrity of various oxidative pathways of hepatocytes. Lidocaine is a highly sensitive indicator of hepatic dysfunction. This test is applicable to assessment of stage and prognosis of the liver disease, to timing of the liver transplantation, and to assessment of the pretransplant prognosis in the end-stage of chronic liver disease. Formation of the major lidocaine metabolite monoethylglycinexylidide (MRGX) depends on the hepatic cytochrome P-450 activity and on the liver blood flow. PMID- 11192754 TI - [Discussion of the article by T. Haas "Ethics and statistics--difficult approaches to data"]. PMID- 11192755 TI - [60 years' of antibiotics--resistance: a time bomb for the third millenium]. AB - More then 50 years of antibiotic era has brought to clinical use many antibiotics with, specific and also with broad spectrum activity. Excessive use of antibiotics brought and brings serious problems--the resistance of many important bacteria and so the loss of effectivity of these scarce substances. Significant negative role in this process has the transferability of the resistance genes between bacteria. Bacterial strains are able to accept block of genes for multiresistance, exchange them inter species and spread to susceptible ones. There is an important task for the 3rd millennium to reduce the prevalence of the antibiotic resistance. Changes of the empiric treatment regiments (reduction in antibiotic use, antibiotic rotation, infection control, monitoring of resistance) and the strict hospital hygiene could help to solve the problems of antibiotic resistance in the future. PMID- 11192756 TI - [Resistance to cytostatics in hematologic neoplasm cells. Part III]. AB - Resistance to cytotoxic drugs is a serious drawback in the treatment of patient with tumours, both of the haemopoietic and non-haemopoietic origin. The cytotoxic effect of drugs on the malignant cells manifests as the process of apoptosis. In the resistant malignant cells, apoptosis becomes prevented by several mechanisms. The multidrug resistance (MDR) is one of the principal mechanisms when the cancer cells develop resistance to multiple chemically and functionally unrelated cytotoxic compounds. The decrease of the cytotoxic drug concentration at the molecular target site may come from activation of some efflux membrane systems participating in the transport of cytotoxic drugs out of the cell (e.g. Pgp, MDR, and LRP). Another mechanism of resistance is the increased enzymatic detoxification of the drug by glutathion-S-transferase system. Changes in the molecular target of the cytotoxic drug such as topoisomerase molecule can be also responsible for the resistance. At least two additional mechanisms of resistance of tumour cells were identified. Resistance can come from either deregulation of proapoptotic mechanisms in tumour cells or by increased activity of reparation processes which control the damaged molecule of DNA. Several methods that detect the cause of resistance in distinct cell populations have been developed. The great effort is now focused on both the detection of mechanisms of the resistance and on the clinical procedures of overcoming the resistance to cytotoxic drugs. PMID- 11192757 TI - [High-dose chemotherapy in the treatment of children with malignant lymphoma]. AB - BACKGROUND: Children with primary refractory or recurrent malignant lymphoma have usually poor prognosis. Less than 10% of those, who were treated with conventional-dose regimens had survived for 2 years. In an attempt to improve the outcome for these patients, we explored the role of consolidation high-dose chemotherapy with autografting. METHODS AND RESULTS: Forty-five patients with poor-prognosis lymphoma, of whom 27 were males, underwent megatherapy between January 1992 and December 1999. High-dose chemotherapy was indicated in patients with poor initial response to first-line chemotherapy (14 cases) or in the relapse (31 cases). The group consisted of 27 patients with Hodgkin's disease and 18 patients with non-Hodgkin's lymphoma. The median age was 14.7 years. The conditioning for Hodgkin's disease patients contained cyclophosphamide, etoposide and busulfan or carmustine. Patients with non-Hodgkin's lymphomas received cyclophosphamide, etoposide and busulfan or total body irradiation. Bone marrow was used as the source of haemopoietic stem cells in ten patients, peripheral blood in twenty-eight, and both sources were used in seven patients. After the median follow-up of 47 months, the final survival was 61%. Eleven patients died of the disease progression, four of the infectious complications, one at a car accident. Median time to relapse after the transplantation was 7.5 months. CONCLUSIONS: Further improvement of these results will require earlier transplantation, improved preparative regiments or early posttransplant immunotherapy. PMID- 11192758 TI - [Determination of soluble HLA class I molecules in children in bone marrow transplantation]. AB - BACKGROUND: sHLA molecules are the soluble forms of their membrane bound counterparts. sHLA class I. were recently reported to be a useful marker in the prediction of graft versus host reaction (GVHR) in adults. To confirm these presumptions in children we measured sHLA class I. serum levels in children after allogeneic bone marrow transplantation (BMT). We also investigated the levels of sHLA in the supernatants of mixed lymphocyte cultures (MLC) as possible predictors of GVHR prior to BMT. METHODS AND RESULTS: Group of 6 investigated children included 1 child with severe combined immunodeficiency, 3 children with acute lymphoblastic leukemia, 1 with severe combined immunodeficiency, 3 children with acute lymphoblastic leukemia, 1 with severe aplastic anemia and 1 with non Hodgkin lymphoma. The period of follow up varied from 15 days to 21 months according to the course of the disease. In the prediction of GVHR the levels of sHLA were measured in 5 children with acute leukemia in supernatants of MLC and the results were compared with the grade of GVHR classified according Seattle criteria. Soluble HLA class I. molecules were evaluated by ELISA. Rise of the levels of sHLA preceded 1-2 days the clinical signs of GVHR, however, it could not be distinguished from the occasional rise of a different cause. The levels of sHLA found in the supernatants of MLC showed individual results, which did not correspond to the level of cytokines in the same culture, or to the grade of GVHR observed. However, twice higher levels of sHLA in the culture of donor lymphocytes correlated with the lethal outcome of GVHR despite the fact that the donors were HLA identical siblings. CONCLUSIONS: The usefulness of sHLA levels as the predictors of GVHR has to be interpreted with great caution, but they can be used as a part of the mosaic composed of the clinical image and other laboratory results indicating GVHR. The predictive value of sHLA in supernatants of MLC is still to be evaluated. PMID- 11192759 TI - A high occurrence of BRCA1 and BRCA2 mutations among Czech hereditary breast and breast-ovarian cancer families. AB - BACKGROUND: About 5-10% of breast and ovarian cancer can be of hereditary origin. Germline mutations in BRCA1 or BRCA2 and probably other yet unknown genes may cause predisposition to these cancers. METHODS AND RESULTS: Molecular genetic testing of BRCA1 and BRCA2 genes in 21 high-risk breast and breast/ovarian cancer families was performed in order to find the types and the frequency of mutations in the South Moravian region of the Czech Republic. A germline mutation was found in 12 of 21 tested families (57%), 9 mutations in BRCA1 gene and 3 mutations in BRCA2 gene. In 4 unrelated families the same germline mutation in the BRCA1 gene (5382insC) was identified. In 12 families diagnosed with breast cancer only syndrome 3 families harbouring BRCA1 mutations and 3 families harbouring BRCA2 mutations were found. In 9 families with breast-ovarian cancer syndrome 6 families carrying BRCA1 mutations were detected. CONCLUSION: Molecular genetic testing of BRCA1 and BRCA2 genes in high-risk women with breast/ovarian cancer is effective in determining genetic predisposition to cancer. Spectrum of mutations found in both genes is variable and further investigation is needed for estimation of more frequent or "founder" mutations. The genetic counselling and preventive clinical follow-up of gene carriers has to be part of the genetic program. PMID- 11192760 TI - [Disorders of urinary acidification in patients with monoclonal gammapathies]. AB - BACKGROUND: In patients with monoclonal gammapathy (MG), renal impairment becomes the frequent complication. At the same time, its exact pathogenetic mechanism remains to be identified. We tried to detect urinary acidification defect that may become the first sign of the kidney parenchymal injury. The goal of our work was to estimate the incidence of the acidification impairment, the contribution of proximal and distal types of renal tubular acidosis and the dependency of the defect on the type of light chain paraprotein. METHODS AND RESULTS: In the group of 21 patients aged 38 to 82 years (14 females and 7 males) with monoclonal gammapathy accompanied with creatinemia lower than 180 micromol/l, the short acidification test was performed (calcium chloride was administrated and the urinary acidity was monitored). Renal tubular acidosis was diagnosed in those patients whose urinary acidity after the CaCl2 administration did not reach pH 5.25 or less. The control group consisted of 19 volunteers (6 males and 13 females) with normal renal functions. Results of the tests in MG patients and in control persons were compared using the unpaired Student's t-test. In 11 patients (52.4%) the urinary acidification defect of the incomplete type was detected. Eight of these patients (38.1%) had the distal and three (14.3%) had the proximal type of impairment. Eight patients with the acidification defect had the paraproteinuria kappa and four of them had that of lambda type. In persons without the acidification impairment kappa chains were found in 5 persons, lambda chains in 4 of them. CONCLUSIONS: In our group of MG patients acidification defect occurred in more than half of them. Contrary to the assumed higher nephrotoxicity of the lambda chains, the disturbance was more frequently found in patients with paraproteinemia of the kappa type. PMID- 11192761 TI - [Biochips]. AB - A new revolution technology that may become promising for research, diagnostics and therapy enters into biology and medicine. The basic idea of the biochip technology is to convert the chemistry of life into a static form programmed to monitor genes, proteins and relations between them. Biochip programmed by known sequences of DNA/RNA or proteins can recognized the real genes, mutations, levels of expression,... Biochip technology is highly effective method that allows monitoring of thousands of genes/alleles at a time in computerized automatic operations with minimal volumes of necessary reagents. Biochips promise an important shift in molecular biology, DNA diagnostics, pharmacology, research in carcinogenesis and other diseases and also the possibility of a better understanding of the world of biology in its globality. PMID- 11192762 TI - [The compartment syndrome--still a threat in traumatology]. AB - Paper presents current opinions on the definition, causes, classification, diagnosis and treatment of the compartment syndrome (CS). The development of CS after the long-bone fractures of the lower extremity and also after the limb operations or trauma without fracture is discussed. The importance of early and correct diagnostics and treatment is also revealed. Authors present several case reports and they stress the importance of early fasciotomy when necessary. PMID- 11192763 TI - [Gene expression in white blood cells in chronic myeloid leukemia]. AB - BACKGROUND: The new technologies that have the DNA laboratory over recent years and the general progress in knowledge of the human genome, have allowed the simultaneous observation of the activity of a large number of genes. Chronic myeloid leukemia is characterized with abnormal tyrosine kinase activity of the fused bcr/abl gene, which is most often product of translocation between chromosomes 9 an 22. It is as yet unknown whether this is the only and sufficient cause of the disease, or whether other supporting and co-active abnormalities exist. It is also not yet clear whether an increase of proliferating activity or reduced programmed cell death plays the dominant role. The aim of this study was to make further steps in resolving the question as to which of these hypotheses fits better. METHODS AND RESULTS: Membrane macroarrays (Clontech 7742-1: Human Cancer cDNA Expression Array with 588 gene probes) were used throughout the study, on which cDNA reverse-transcribed from total RNA in turn isolated from peripheral white blood cells and labelled with 32P was hybridized. Cells obtained from 5 patients with confirmed diagnoses by cytogenetic and molecular (bcr/abl) analyses, but who had not yet been treated by chemotherapy, were the source of the material. In some cases mononuclears and granulocytes were also isolated by Ficoll-Paque centrifugation. Radioactivity was detected by autoradiography or by a Phosphorimager (Fujifilm FLA-2000). Comparison with normal gene expression (healthy donor) was made by subtraction using Clontech AtlaImage 1.5 software. Although changes of expression of identical genes were not observed in all of patients examined, the majority of them were concordant. Values at least double those of the controls applied to the activity of c-jun N-terminal kinase, MMP-8, MMP-9, integrin alpha E, integrin beta and PDGF, whereas the expression of ZAP 70, IRF1, MCL-1, STAT 5B, RARA, CDC25B, RPSA, TNFR decreased. Increases of PCNA, MMP-17, CD59, rho G, CRAF1 and PIG7 or decreases of notch, caspase 8, caspase 4, interleukin 6 receptor, rho B and TIMP1 were observed only in some cell samples. CONCLUSIONS: It seems that some maturation processes and transmembrane signalling are blocked, as well as the effectors of apoptosis. On the other hand, the reduced activity of ZAP-70, IRF1 and MCL-1 also indicated that proliferation breaks were weakened. The involvement of both processes-released replication and ineffective apoptosis--was evident; the problem of bcr/abl gene fusion being the necessary first and sufficient step on the way towards developing chronic myeloid leukemia, however, remained unresolved. PMID- 11192764 TI - [Serum leptin levels and soluble leptin receptors in female patients with anorexia nervosa]. AB - BACKGROUND: Leptin action in peripheral tissues is enabled by an interaction with specific transmembrane receptors. Several of leptin receptor isoforms were identified, including soluble leptin receptor isoform structurally identical to extracellular domain of the the long leptin receptor isoform. The soluble receptor isoform is released to the circulation and acts probably as leptin binding factor. The aim of our study was to measure serum concentrations of the soluble leptin receptor in patients with anorexia nervosa and in the control group of healthy women. Relationships of soluble leptin receptor levels to body mass index (BMI), body fat content, serum leptin, TNF-alpha and insulin levels were also studied. METHOD AND RESULTS: 16 patients with anorexia nervosa and 16 age-matched lean healthy women were included into the study. All of the subjects were measured and weighed, the body fat content was estimated from the skinfold thickness measurement. The blood for the determination of leptin, soluble leptin receptor and other hormonal parameters was obtained from all subjects after the overnight fasting. BMI, body fat content, serum leptin and insulin levels in patients with anorexia nervosa were significantly lower than in the control group (BMI: 14.98 +/- 2.32 vs. 22.21 +/- 2.48, p < 0.01, % fat content: 16.43 +/- 4.56 vs. 27.19 +/- 4.59, p < 0.01, leptin: 1.37 +/- 1.85 ng.ml-1 vs. 7.19 +/- 3.49 ng.ml-1, p < 0.01, insulin: 12.97 +/- 2.89 mU.l-1 vs. 17.09 +/- 5.57 mU.l-1, p < 0.05). Serum soluble leptin receptor levels in patients with anorexia nervosa were significantly higher compared the to control group (24.67 +/- 8.3 U.ml-1 vs. 15.71 +/- 2.79 U.ml-1, p < 0.01). No significant differences in serum TNF-alpha levels between the groups studied were found. Serum leptin levels in both groups correlated positively with BMI and body fat content. Serum soluble leptin receptor levels in both groups correlated negatively with BMI only. No statistically significant relationships between serum soluble leptin receptor levels and the rest of parameters studied were found in any of the groups studied. CONCLUSIONS: Serum soluble leptin receptors levels in patients with anorexia nervosa were significantly higher in comparison with the healthy subjects. Except of the negative correlation between serum soluble leptin receptor levels and BMI no statistically significant relationships between serum soluble leptin receptor and the rest of parameters studied were found. PMID- 11192765 TI - [Determination of biological age--a group of biophysical tests]. AB - BACKGROUND: Biological age is defined as real state of organism with respect to the processes of aging. From the gerontological point of view, the methodology of determination of biological age is a tool for verification of theories. The role of biological age determination in medicine is wide. It consists, among others in the assessment of the efficiency of anti-aging interventions or in detection of premature aging. Many different batteries of methods for the measurement of biological age were developed till now. The currently applied methods are not standardized and they are, as a rule, significantly time-consuming. METHODS AND RESULTS: The goal of the work was to develop a routine method for biological age determination. Simplicity and reproducibility of measurements was stressed. The result of our work is a set of 7 biophysical methods. Some of the methods are newly developed (measurement of rheological properties of the skin), others are modified classical methods (measurement of accommodation of eye, perception of high frequencies of sound, reaction times). CONCLUSIONS: The battery of biophysical test for the routine biological age assessment was developed in our laboratory. The information is processed by computer, using multiple linear regression analysis for obtaining the best assessment of personal biological age. The duration of measurement is roughly 120 min. PMID- 11192766 TI - [Carbohydrate-deficient transferrin. Methods of determination and clinical significance in the detection of alcohol abuse]. AB - Last decade witnessed the increasing use of serum levels of carbohydrate deficient transferrin (CDT) as a highly specific and sensitive marker of chronic alcoholism. This paper deals with the explanation of the physiological principle of the test and the development of laboratory techniques of CDT measurement. The evaluation of the state-of-art of CDT tests is based on published data as well as on the practical experience of the author with three commercial diagnostic kits. The second part of the review article draws attention to some still open questions of how to harmonize the different methodologies used. The use of the CDT measurement in various clinical settings, the specificity and sensitivity of CDT in different population samples and/or in comparison with already established markers such as GGT is discussed. PMID- 11192767 TI - [Bladder dysfunction is often a cause of therapy resistant enuresis. The condition should be removed from the group of psychiatric diagnoses]. PMID- 11192768 TI - [Oculoplastic surgery implies restoration to "normalcy". Cosmetic surgery is performed only for congenital malformations or disease]. AB - Ophthalmic plastic or oculoplastic surgery is the current term for the surgical treatment of disorders of the eyelid, the lacrimal apparatus and the orbit. The most frequent causes are congenital malformations, malpositions, abnormal motility, tumors and injuries. A good functional result with the best possible appearance is the goal; cosmetic surgery is performed only when the underlying cause is a malformation or disease. Several specialties have qualifications relevant to this field or parts of it; this article describes the tasks of an ophthalmologist working in this field and what he can accomplish. PMID- 11192769 TI - [Use the entire "analysis package" when investigating patients with venous thrombosis! Don't forget the relatives...]. AB - During the last few years several genetic markers have been discovered that contribute to an increased risk of venous thrombosis. Patients who have several genetic markers are at a considerably higher risk of being affected than patients with only one marker. Recommendations are made as to which patients should be investigated, with appropriate laboratory analyses, when an increased risk of venous thrombosis is suspected. Most of the analyses can be done even if the patient is undergoing warfarin treatment. PMID- 11192770 TI - [Drugs or enuresis alarm can help more children stay dry at night. To wet oneself is distressing and taxing for self-confidence]. AB - Monosymptomatic primary nocturnal enuresis (PNE) is commonly treated with desmopressin (Minirin), resulting in dry nights for approximately 70-85 percent of affected children. However, nocturnal enuresis is sometimes accompanied by signs of bladder dysfunction. A history of urgency, frequency, daytime wetting or urinary tract infection may indicate the presence of a hyperactive, unstable bladder. In these cases, desmopressin in combination with an anticholinergic drug (i.e. oxybutynin; Ditropan) given at bedtime, or desmopressin and a bed alarm, will increase the number of patients with dry nights. This therapy can now be offered not only by pediatricians but also by general practitioners. PMID- 11192771 TI - [Multiple pregnancy is the most known risk of fertilization in vitro. Review of the relevant literature]. PMID- 11192772 TI - [Varices and venous insufficiency--therapeutic philosophy prior the 2000's]. AB - Varicose veins represent everything from a cosmetic problem to a risk of venous leg ulcers. Predicting the risk of complications has been difficult, not least due to less than satisfactory diagnostic procedures. Recent investigations have pointed out some important new concepts: Superficial venous incompetence may give rise to an ulcer, and such an ulcer may be prevented by varicose vein surgery. Recanalization and stenting may be useful in treating chronic iliac and caval venous occlusions; however, long-term outcome is yet to be established. Venous diameter can be reduced, thus effecting valve competence. To what extent this result is long-lasting is not known. Neither has the method been attempted on deep veins. Clinical diagnosis is never sufficient in cases of suspected chronic venous incompetence. The minimum requirement is the use of a hand-held Doppler. Frequently, a more detailed ultrasonographic analysis is required, and for a global assessment of venous function, plethysmographic techniques are useful. Primary health care may contribute effectively to the care of venous leg ulcers. PMID- 11192773 TI - [Feministic research means that all research is political]. AB - The article is a review of different trends and epistemologies in women's studies/feminist research within the field of medicine. In the beginning of the 1980s, women's studies entered the field of medicine in the Nordic countries. They are now a part of the feminist research that has been established within most sciences both nationally and internationally. The gender power relation and its impact on health--first of all women's, but in extension also men's--has been in focus. Moreover, science itself, its limits and possibilities, and the kind of knowledge it produces, is discussed. In this respect, feminist theory of science is a useful tool. PMID- 11192774 TI - [Artificial respiration at home seen in a 5-year perspective. Established treatment, but remarkable differences among the counties]. AB - The Swedish prevalence of home mechanical ventilation is 8.2 per 100.000 with 10% annual increase. There is a large span (20 vs 2 per 100.000) between "top level" and "low level" counties, in spite of Sweden's homogeneous publicly financed system for provision of health care. The largest prevalence difference was found in patients with obstructive sleep apnoea syndrome (Pickwickian type), but their blood gas and lung function data were identical in top-level vs low-level counties. These data refute the hypothesis of overprescription in top-level counties. We conclude that the most probable explanation is under-recognition of patients in low-level counties. PMID- 11192775 TI - [Computer tomography or hospital monitoring in brain concussion? Current conclusions in a new SBU-report]. PMID- 11192777 TI - [Literature can help to train the empathic ability]. PMID- 11192776 TI - [Will genetics make a revolution in health care? Skepticism concerning the exaggerated expectations]. PMID- 11192778 TI - [Forensic psychiatry and criminal politics--ethics must be discussed prior to the introduction of a new system]. PMID- 11192779 TI - [A final reply on cervix cancer screening: nobody is disputing its effects, but... ]. PMID- 11192780 TI - [Revise the control of communicable diseases in connection with immigration to Sweden!]. PMID- 11192781 TI - [Sleep apnea--who is actually taking care of this syndrome?]. PMID- 11192782 TI - [Successful treatment of vocal cord paralysis]. PMID- 11192783 TI - [Is the concept of general practitioner an insult?]. PMID- 11192784 TI - [Vitamin B12--good, better, best! ]. PMID- 11192785 TI - [On Swedish front line research]. PMID- 11192786 TI - [300 videothoracoscopy procedures--personal experience]. AB - Videothoracoscopy and video-assisted thoracic surgery are by now already standard therapeutic procedures in thoracic surgery. The authors submit their experience with the method after 300 thoracoscopic operation at the surgical clinic of the Faculty Hospital in Plzen from the end of 1993 to the beginning of 2000. The main indications for this mini-invasive procedure is the treatment of spontaneous pneumothorax, diagnostic biopsy in pulmonary dissemination of obscure etiology, diagnosis and treatment of pleural exudates and elimination of minor peripheral pulmonary lesions. The authors discuss different surgical procedures in the most frequent diagnoses, their advantages and risks, indication criteria, complications. Attention is also paid to the causes of 10% conversions. In case of treatment of a spontaneous pneumothorax the authors consider videothoracoscopy as the method of first choice, while in case of primary carcinoma of the lungs they recommend the classical procedure. Other possibilities for the wider application of thoracoscopy and its development in their own department include in particular traumatic thoracic surgery. PMID- 11192787 TI - [Assessment of metastatic potential of pulmonary carcinoma]. AB - The authors evaluated in a group of 25 patients after radical lung resection on account of a non-small cell carcinoma the correlation between tumour grading, invasion into lymphatic and blood vessels, proliferation markers (Ki-67, PCNA), ploidy, cell polymorphism and mitotic cell activity of the lung tumour and the lymphogenic or haematogenic metastatizing proved before or during surgery. From the investigation patients after induction chemotherapy were eliminated. It was of interest that the great majority of investigated parameters was positive or elevated in patients with lymphogenic or haematogenic metastases. Conversely in patients where the majority of these parameters was negative on the day of the operation, no metastases were detected. In the group of patients where the investigated indicators were positive and no metastasis was found, similarly as in both previous sub-groups, the author will continue to follow-up the following: recurrence, median survival and five-year survival. From the assembled parameters a table was prepared stratifying the risk of metastases. PMID- 11192788 TI - [Transmyocardial laser revascularization of the myocardium and coronary reconstruction without extracorporeal circulation]. AB - The authors report their experience with myocardial revacularization using transmyocardial laser revascularization combined with aortocoronary reconstruction without the use of extracorporeal circulation. The discussion section addresses indications for the procedure, operative tactics, the benefits and limitations of the above technique. PMID- 11192789 TI - [Simultaneous occurrence of acute myasthenia gravis and acute polymyositis in 3 patients and in 2 patients also associated with a thymoma]. AB - In the Slovak Centre for Neuromuscular Diseases 768 patients with myasthenia gravis are on the records. 112 myasthenics (14.5%) have another associated autoimmune disease. Most frequently a combination with an autoimmune disease of the thyroid gland or rheumatoid arthritis is involved. Extremely rare is the concurrent manifestation of the acute form of mysthenia gravis and acute polymyositis, observed by the authors in three patients,incl. two associated with a thymoma. In all three patients the disease had a serious clinical picture which called for controlled ventilation and a nasogastric tube. From the prognostic aspect rapid and correct diagnosis and early adequate treatment--combined immunosuppressive treatment (prednisone, azathioprin) is most important, incl. large i.v. doses of methylprednisone, repeated plasmaphereses, i.v. administration of human immunoglobulin, 0.4 g/kg body weight for a period of five days and optimally timed thymectomy with removal of the thymoma. PMID- 11192790 TI - [Extensive defect in the inguinal region and damaged femoral arteries. Single stage reconstruction of the arterial supply and skin coverage. Case Report]. AB - The authors present an account on a patient with extensive damage of the tissue in the area of the right groin with complete severing of the artery and vein. After control of the infections they reconstructed the arterial supply and skin cover in one stage. They used a PTFE prosthesis with an extraanatomical localization and a muculocutaneous flap formed from the musculus rectus abdominis on a caudal stalk. PMID- 11192791 TI - [The harmonic scalpel in thyroid surgery]. PMID- 11192792 TI - [Kidney transplantation from living donors]. AB - From Jan. 1, 1994 till August 31, 1999 in the Transplantation Centre of the F. D. Roosevelt Hospital and Policlinic 202 transplantations of the kidneys were made, incl. 11 from live donors. The survival of patients and renal grafts in our group is 100%, i.e. all transplanted kidneys are so far functional. In transplantations of kidneys from dead donors the one-year survival of grafts was 85% and the 5 year survival only 70%. During removal of kidneys from live donors we had only one minor complication--a surface infection of the surgical wound. The authors describe their own experience with assessing the indication criteria, criteria for selection of the most suitable donor-recipient pair. Consistently with work of authors from abroad, they consider transplantations of the kidneys from live donors as one of the best alternatives how to increase the number and quality of renal transplantations and to prevent thus an increase of the number of patients on the waiting list. PMID- 11192793 TI - [The current method of staging gastrointestinal (GIT) tumors]. AB - The authors analyzed in a retrospective study the stage of carcinomas of the stomach and colorectum in their material. In 1996-1998 they operated 35 patients with gastric tumours and 77 patients with colorectal cancer. In both groups they operated more than 50% of the patients in the IIIrd or more advanced stage of the disease. 22.8% gastric tumours and 19.5% colorectal tumours were operated in the acute stage. The situation in the group is alarming, it is essential to improve the early diagnosis and thus also treatment in all links of the chain: patient- attending physician--surgeon--society. PMID- 11192794 TI - [Methods of surgical treatment of necrotizing pancreatitis]. AB - The authors present a group of 49 patients operated on account of acute necrotizing pancreattis in 1990-1999. They describe the indications and methods of treatment. The principle of treatment was careful necrosectomy with an additional procedure which involved rinsing and drainage of the omental bursa, laparostomy ("open packing") or a combination of both methods. They re-operated 20 patients where they performed a total of 57 re-operations. Fifteen patients died (30.6%) which according to the literature corresponds to the mortality quoted in this group of the most severely affected patients. PMID- 11192795 TI - [Radical treatment of rectal cancer]. AB - The authors present an account on radical resections of the rectum in 73 patients during 1991-1995. A radical operation with excision of the mesorectum was performed 69 times, local excisions 4 times. Five-year survival was recorded in 57.90% patients, local relapses were recorded in 10.14% patients. Remote metastases or generalization of the disease was found in 18.84% patients. Adjuvant treatment was administered to 74% patients. PMID- 11192796 TI - [Compression therapy of leg ulcers]. AB - The authors present a group of 76 patients with chronic venous insufficiency in the stage or crural ulceration. After staging of the disease (C 6, E prim, E sec, A sup. pr. ref., P re) in the first stage they used a conservative approach, the method of compressive bandages: either an elastic bandage or zinc-glue bandage (Varolast). 49 patients were cured by conservative treatment (64.5%) in the course of 5 months. 12 patients were indicated for surgery (15.8%). Thus the authors cured finally 80.2% patients. A relapse was recorded in 6 patients (7.8%) and in 9 patients treatment failed (11.8%). For treatment with zinc-glue bandages they recommend patients without obstruction in the deep venous system, with large chronic ulcers and associated oedema of the whole leg. PMID- 11192797 TI - [Prevention and therapy of dehiscent laparotomy wounds]. AB - Dehiscence of laparotomic wounds is always unpleasant, starting with the resentment of the patient and the lack of confidence leading as far as complete negation of a favourable result of the operation. Due to lack of more suitable materials we elaborated ten years ago our own technique which we use nowadays for treatment but in particular for prevention. We feel that it could be a certain asset because it is simple and financially feasible. PMID- 11192798 TI - [Treatment of ingrown toenails]. AB - Surgery of ingrowing toe nails are one of the most frequent operations in ambulatory practice. It is well known that a minor operation which relieves the patient of his complaints is appreciated more than the most complicated operation. Based on the article of Dr. Krticka we wish to present our own modification of an operation called Klapp's operation. We found that the results when using a modified vertical U stitch are better than when the classical technique is applied. PMID- 11192799 TI - [Alexithymia and depression in eating disorders]. AB - Patients suffering from eating disorder show elevated rates of alexithymia and depression. We compared alexithymia and depression ratings for non-hospitalized women meeting DSM IV criteria for anorexia nervosa (n = 32) and bulimia nervosa (n = 32) to healthy women (n = 74). Alexithymia was evaluated by the Toronto Alexithymia Scale (TAS-20) and depression by the Hospital Anxiety and Depression Scale (HAD). We found that TAS and HAD scores were significantly higher in anorexic compared to bulimic patients, although alexithymia and depression, as evaluated, were significantly and positively correlated with each other (r = 0.53, p = 0.001). Finally, a logistic regression with alexithymia and depression as independent variables showed a strong correlations between the HAD ratings and anorexia, but no correlations between TAS score and the eating disorder subgroups. In eating disorder patients, alexithymia, as evaluated by the Toronto Alexithymia Scale, seems to exhibit a thymo-dependent component which could be secondary to concurrent depression. Through recent studies and results of our research, we analyze and give several interpretations which may explain this correlation between alexithymia and depression. PMID- 11192800 TI - [Psychometric properties of a new instrument for evaluating quality of life, the WHOQOL-26, in a population of patients with neuromuscular diseases]. AB - This study describes the principal psychometric properties of the French version of the WHOQOL-26, a short version (26 questions) of the WHOQOL-100, which are World Health Organization instruments for evaluation of quality of life (QOL) which include four dimensions (physical, psychological, environmental, social relations). The use of this tool with psychiatric patients is discussed. Collection of data was performed during a national inquiry on persons with neuromuscular disorders. The population included 2,102 subjects (mean age 42.9 +/ 15 years). Ten different clinical entities were represented, which differed in the type of lesion of the motor unit, the permanence and localization of the loss of muscle strength, the progression of the respiratory deficit, the moment of its occurrence and seriousness of prognosis. This questionnaire was well-adapted to the study population (weak effect of extremes) and was well-accepted (only 5% non responses). Compared with the long version, homogeneity is less pronounced, but remains acceptable (the item-scale correlation is superior to 0.40 for 66.7% of some items), which is the same as the reliability (Cronbach's alpha coefficient always over 0.65). The sensitivity in relation to the diagnosis is verified for all four dimensions (p = 0.05). The concurrent validity, studied using general QOL evaluation scores, satisfaction with health, and the importance of repercussions of incapacities on daily life was also globally demonstrated (p < 0.0001). PMID- 11192801 TI - [Validation of the French version of the Raine Schizotypal Personality Disorder Questionnaire--categorial and dimensional approach to schizotypal personality traits in a normal student population]. AB - Most of existing self-report measures of schizotypal personality assess only few of the nine traits of Schizotypal Personality Disorder (SPD) according to DSM III R or DSM IV. The Raine's Schizotypal Personality Questionnaire (SPQ) is one of the most widely used questionnaire for SPD diagnosis. This well adapted tool for screening SPD in large samples from general population allows simple and quick evaluations by the mean of 74 items and nine sub-scales exploring DSM IV criteria of the trouble. With the original sample of American students, Raine found SPQ to have high internal reliability (0.91) and reported cutoffs for the top and the bottom ten percents of SPQ scores at respectively 41/74 and 12/74. We reported here the validation study of the French version of the SPQ in a sample of 232 students (males: n = 107; females: n = 125; mean age: 21.17 +/- 1.47; mean educational level: 13.36 +/- 1.06). The French version has high internal reliability (SPQ total: Cronbach's alpha = 0.91; SPQ nine subscales: Cronbach's alpha = 0.57 to 0.76). The ten percent high and low cutoff scores on the distribution of SPQ scores are respectively 40/74 and 7/74 for the total sample. However, gender differences are observed: 38/74 and 9/74 for females; 42/74 and 6/74 for males. A Principal Component Analysis (PCA) confirms the high internal reliability. Moreover, PCA evidences a three-factor model of schizotypy reflecting "positive or cognitive-perceptual", "negative or social interpersonal", and "disorganization" latent factors. These results replicate previous works on the topic with the same instrument. PMID- 11192802 TI - [What information do patients with schizophrenia have about their illness and treatment?]. AB - Improved compliance with antipsychotic medication is a major issue in schizophrenic management. For this purpose educational programs have been used, but up to now, little or no information has been gathered or published in France concerning schizophrenic patients' opinion on information they have about their disease and their treatment. Thus we conducted a survey in concert with 78 psychiatrists from the French psychiatric health service. From this cross sectional survey we assessed 336 outpatients (male: 72%; mean age: 36 +/- 10.4 years) with schizophrenia according to the DSM IV (paranoid sub type: 57%, disorganized: 12%, catatonic: 1%, undifferentiated: 12%, residual: 18%). The mean duration of the illness was 11.6 years (sd: 8.5) and the mean duration of the follow up with the same psychiatrist was 5.4 years (sd: 5.1). Patients completed a questionnaire which assessed their level of information on mental illness and treatment. The diagnosis of schizophrenia has been told to their patients by 39% of the psychiatrists, and treatment has been explained to the patients by 96% of the practitioners. Results indicate less than half of the patients (45%) felt ill, only 46% thought they knew their illness well or very well (nevertheless only 31% of them named spontaneously the diagnosis of schizophrenia or psychosis), and 61% considered that they had been given sufficient information. Most of the patients (79%) were persuaded that their treatment was useful, and 75% of patient were completely satisfied with their treatment. Surprisingly 92% reported taking their medication regularly. Most patients think that a high level of information about their illness (74%) and treatment (79%) help them to cope better with their schizophrenia. Analysis performed according to patients characteristics indicated that paranoid patients felt more ill (p = 0.035) than others, thought to know less about their illness (p = 0.0065), and were less satisfied with their treatment (p = 0.04) and their level of information (p = 0.03). Patients with a duration of their illness longer than 10 years were more convinced of the utility of their treatment (p = 0.02) and had debated more on the choice of their treatment with their psychiatrist (p = 0.047). Patients older than 35 years were more satisfied with their information (p = 0.002). More patients with atypical antipsychotics accepted to take their treatment on a regular basis (p = 0.035) compared to patients under classical neuroleptics. This survey underlines that mental health consumers' opinions can be obtained even in the field of schizophrenia, and argues in favour of further such investigations. It also highlights the need for educational programs on schizophrenia and antipsychotic medications. PMID- 11192803 TI - [Epidemiologic, clinical and institutional analysis of 2 outpatient psychiatric patient management facilities]. AB - A cohort of 100 patients was followed up over 6 months in two extra-hospital closed clinics. One of them offers free entrance care while the other one offers structuring contractual care for psychotic patients; 57% of the patients are psychotic and 27% suffer from neurosis; 8% of the patients have a borderline undetermined diagnosis. The mean age was 43 years. The youngest was 18 and the oldest 75. There were more males (59%) than women (41%). There were no significant difference between socio-medical and self patient reference. The relative stability of the attendance shows the interest of the population toward the clinics. Most of the care for psychotic patients were done in the clinic which offers self entrance care. It happens that the theoretical distinction between the two clinics does not appear on the field. Psychotic patients seem to prefer free entrance care than structuring contractual care which is theoretically destinated to them. The analysis of health personnel competence could help understanding. However, we can ask ourself about care protocols in psychiatry, and especially contractual care for psychotic patients in our environment. PMID- 11192804 TI - [Quality of life of children: importance of its evaluation. Comparison of children in good health with those at risk (psychological, social, somatic)]. AB - A multicentric study was performed in France and Spain: 490 children were evaluated with a previously validated questionnaire including open-ended questions and structured response format questions. Children are either in good health or suffering from somatic diseases, psychological problems or social difficulties; 38% of the children are Spanish, 62% are French; the questionnaire validation was checked again, and confirmed. Children are happy about their leisure, and unhappy when separated from their families. Among the factors affecting the answers to the structured format questions the most important are the social difficulties and to a lesser extent the psychological problems. Somatic diseases impair the child's quality of life in Spain. Children differ according to the country where they live. Among children in good health, Spanish children report a better quality of life than French children. Open-ended answers were only studied in France. They were very different when children with social difficulties or psychological problems filled out the questionnaire and were compared to children in good health or with somatic diseases. Both children with psychological and social difficulties mention more often the relationship domain. Children with social problems never mention their activities as a source of happiness. PMID- 11192805 TI - [Chronobiological paradigms of mental life and clincial neurosciences]]. AB - Circadian fluctuations of normal and abnormal behavioural processes have been classically reported from statistically validated chronograms (averaged displays of data as a function of time). Going more deeply into the research with rhythmometric investigations reveals that the temporal organization of psychophysiological functions involving several oscillatory systems may compose possible circadian paradigms of brain integration and pathological chronorisk for clinical neuroscience (seizure susceptibility for epilepsy and related states, brain circulatory disturbances, stress-related events, emotional or affective manifestations, and psychosomatic disorders). Rhythmometrically analyzed, the temporal fluctuations of behavioural events tend to indicate that cerebral integrations are circadian, circaseptidian or infradian stage-dependent processes whose chronobiologic characteristics are possibly predictable on the basis of mathematical models. More generally, the present study reveals that: 1) several neurological or psychiatric disorders are directly or indirectly concerned with chronobiologic processes, and that 2) cerebral and behavioural time variations can be detected and described in neurology and psychiatry as algorithmically formulatable recurring psychophysiological changes with a waveform validated by inferential statistical computer methods. Such rhythmometric procedures applied to neurological or psychiatric events suggest also the development of new epistemological concepts in the fields of comparative psychophysiology and theoretical neuroscience. PMID- 11192807 TI - [Psychological factors associated in smoking cessation in patients with arterial occlusive disease of the legs]. AB - Few studies have focused on psychological factors involved in the course of peripheral atherosclerosis, particularly in smoking cessation, which is a major point in the outcome of the disease. In this view, we assessed in 19 men hospitalised for intermittent claudication, some personality and emotional characteristics associated with the patients' recent smoking behaviour. Patients included tend to have high scores of state-anxiety and alexithymia (with difficulty to identify and express their emotions), and to benefit from an efficient social support made of few persons. Concerning the smoking behaviour from the past six months, only 8 subjects stopped smoking and 13 subjects made an effort in this way, despite relatively low nicotine dependence scores, severe peripheral atherosclerosis with frequent erection disorders, and awareness of the importance to stop smoking to improve the outcome. Presence of erection disorders, and eventually higher alexithymia scores, may facilitate the smoking cessation. The main reasons explaining the difficulty to stop smoking don't seem to be pharmacologically induced, neither a denegation of the bad effects of smoking on outcome, but more surely a psychological and complex dependence. It would be essential to assess more precisely the psychological characteristics of the patient to propose more efficient treatment. PMID- 11192806 TI - [Executive and amnestic functions of a group of first-degree relatives of schizophrenic patients]. AB - Several lines of evidence seem to indicate that some neurocognitive measures could be phenotypic markers of predisposition to schizophrenia. The aim of this study was to investigate 21 patients with schizophrenia, 51 of their first-degree relatives and 46 nonpsychiatric controls, with a series of tests known to be sensitive to prefrontal cortical damage--the Trail Making Test, part B (TMT B), the Wisconsin Card Sorting Test (WCST) and a verbal fluency test (VFT)- and/or sensitive to temporo-hippocampic dysfunctions: verbal and visual memory and verbal learning tests from the Wechsler Memory Scale-Revised (Wechsler, 1987). Since parents and siblings share on average 50% of their genes with the schizophrenic proband, firstly we predicted that the first-degree relatives' performance would be at an intermediate level between patients and control subjects and secondly, we expected that a higher proportion of relatives than of control subjects would be impaired. The patients demonstrated deviant patterns of neuropsychological performance on the three tests sensitive to frontal dysfunctions and on most of the memory and learning tests. In the relative group, performance on the TMT B, VFT, immediate verbal recall and verbal learning was at an intermediate level between both other groups and significantly impaired compared to control subjects. However, the relative group did not differ from the control group on the WCST, immediate visual recall, and delayed verbal and visual recalls. Furthermore, compared to the control group, the percentages of patients and relatives who scored one standard deviation below the mean control group were significantly higher for the VFT and immediate verbal recall scores. Among all the tests studied, the verbal fluency and the immediate verbal recall appeared to be valuable phenotypic markers of schizophrenia since: (i) their mean scores were poorer in the patient and in the relative groups, (ii) the percentages of patients and relatives with poor performance were higher than the percentage of controls, (iii) these deficits were not due to poorer general intellectual abilities in the relative group, (iv) these deficits did not correlate with anxiety or depression scores. PMID- 11192808 TI - [Value of trimeprazine among hypnotics in a psychiatric facility]. AB - Trimeprazine (TPZ) has been marketed in France since 1959, as tablets and solution containing respectively 5 mg and 40 mg/ml. TPZ is a phenothiazine derivative with known antihistaminic and sedative effects. The first approved indication for TPZ is in the treatment of allergy. However, its frequent sedative effects are undesirable in this indication. The second approved indication is in the treatment of insomnia (5-20 mg/day) and TPZ is an alternative to conventional hypnotics as diazepam, flunitrazepam, zolpidem, butobarbital... Due to the prescription frequency of this medicine in our hospital, we analyzed the naturalistic prescriptions mode and the clinical end point in patients hospitalized for mental illness. On the one hand, using the hospital prescription software, we analyzed: prescriptions frequency, dose regimen and drug associations with hypnotics, anxiolytics and sedative antipsychotics. On the other hand, we came into contact with physicians in order to know their opinion on TPZ and the whole point of that indication. The results showed a very high prescription frequency (139/400 patients; 35%), a marked increase in dose compared to those approved by the French Drug Administration (5-20 mg/day: 5%; 20 200 mg/day: 95%) and main drug association with hypnotics, tranquilizers or antipsychotics, respectively 38%, 65% and 91%. Clinical end points are: non addictive properties and an easily adequation of posology for the drinkable drop form in contrast with tablets. Thus, TPZ appears as a first-line hypnotic in spite of its adverse effects common to phenothiazine (atropinic and antidopaminergic effects) and is a usefull medicine for the treatment of insomnia in psychotic patients. PMID- 11192809 TI - [A case of leukopenia in treatment with risperidone in an adolescent]. AB - The safety and efficacity of atypical antipsychotics in comparison with conventional neuroleptics allow their prescription in children and adolescents who are particularly at risk for developing neurological or cardiac side-effects. Hematological complications of new antipsychotics are less known, except for clozapine treatment in which blood monitoring strategy is well established. We report on a case of risperidone-associated leucopenia in an african adolescent treated for schizophrenia. He developed leucopenia 10 days after starting risperidone therapy (4 mg/day). The cessation of treatment was followed by a normalization of the white blood cell differential count and the rechallenge was positive (2 mg/day). No hematological abnormalities were observed with olanzapine therapy in this patient. Therefore olanzapine may represent a safe therapeutic alternative. We concluded that risperidone therapy may create a risk for leucopenia especially in patients who present a risk of leucopenia for ethnic reasons. We propose hematological monitoring during risperidone treatment. PMID- 11192810 TI - [Study of antisocial personality conforms hypothesis of cerebral organization]. PMID- 11192811 TI - Health claim. For foods that could lower heart disease risk. PMID- 11192812 TI - Robots help surgeons perform more precise surgery. PMID- 11192814 TI - Cell phones & brain cancer. No clear connection. PMID- 11192813 TI - Preventing colon cancer. Screening and early detection save lives. PMID- 11192815 TI - Jesse Gelsinger. PMID- 11192816 TI - Prescription IDs. PMID- 11192817 TI - Single-use device reprocessing. PMID- 11192819 TI - The public's right to know. PMID- 11192818 TI - Counterfeiting couple pays high price for baby formula fraud. PMID- 11192820 TI - Mifepristone for termination of early pregnancy. PMID- 11192821 TI - Home for the holidays: preventing foodborne illness at family gatherings. PMID- 11192822 TI - Screening for prostate cancer by PSA determination: a time for caution. PMID- 11192823 TI - Elevated serum endothelin-1 levels in patients with colorectal cancer; relevance for prognosis. AB - BACKGROUND: It has been demonstrated that the Doppler Perfusion Index (DPI) is increased in patients who are at risk of developing liver metastases from colorectal cancer. It has been postulated that a circulating hormonal factor is involved in the relative vasoconstriction throughout the splanchnic bed. Endothelin-1 (ET-1), a potent vasoconstrictor which has been associated with tumor growth and is produced by colorectal tumors, may play an important role in this phenomenon. In this paper the prognostic value of serum ET-1 in colorectal cancer is discussed. METHODS: Preoperative serum levels of ET-1 were assessed in three groups of patients: group A underwent resection of the colorectal tumor and remained free of recurrence (n=20); group B developed metachronous liver metastases at least six months after colorectal resection (n=14); and group C presented with colorectal cancer and synchronous liver metastases (n=22). RESULTS: The mean (SD) serum ET-1 levels in groups A, B and C were 1.59 (0.41) pmol/L, 1.70 (0.32) pmol/L and 1.85 (0.47) pmol/L, respectively. These values were significantly different from those of healthy controls (1.22 (0.31), p<0.05). Kaplan-Meier analyses revealed no prognostic value of preoperative serum ET-1 levels. CONCLUSIONS: These preliminary results demonstrate that serum ET-1 levels are raised in patients with colorectal cancer. Serum ET-1 levels do not seem to be of prognostic value for survival. PMID- 11192824 TI - Early 5-fluorouracil-induced changes of poly(A) polymerase in HeLa and WISH cells. AB - 5-Fluorouracil (5-FU), a drug with numerous mechanisms of action which has a long term suppressive effect on human cancer cell proliferation, mediates both partial dephosphorylation and inactivation of poly(A) polymerase (PAP) [EC. 2.7.7.19] as detected by immunoblotting analysis and non-specific enzyme assay, respectively, in human carcinoma HeLa and diploid WISH cells at a concentration of 100 microM. When the same experiment is done in the presence of phosphatase inhibitors, 5-FU induced partial PAP dephosphorylation is abolished. Moreover, a cell type modulated, differential response of HeLa cells (5-FU chemosensitive cells) versus WISH cells (drug-resistant diploid cells) is observed. These results suggest that 5-FU induces early direct or indirect changes in the structure and function of PAP and may regulate pre-mRNA cleavage-polyadenylation. PMID- 11192825 TI - Molecular detection of codon 12 K-RAS mutations in circulating DNA from serum of colorectal cancer patients. AB - Point mutations of the K-RAS gene at codon 12 are found in about 40% of cases with colorectal cancer. The diagnostic implications of the detection of these mutations and their clinical utility are still unclear. The aim of this study was to test both the feasibility of the detection of the mutated K-RAS gene in serum and its potential role in colorectal cancer detection and monitoring. Codon 12 K RAS mutations were examined in DNA extracted from the serum of 35 patients with colorectal cancer and were compared with the K-RAS status in the corresponding primary tumor. Molecular detection was performed by the mutant-enriched PCR (ME PCR) assay, a sensitive method capable of distinguishing a small quantity of mutated DNA in the presence of abundant wild-type DNA. The occurrence of mutations was compared with clinicopathological parameters as well as CEA and CA19.9 serum levels. We found codon 12 K-RAS mutations in the tissue of 13/35 (37%) patients. Serum mutations were detected in 5/13 (38.5%) patients with mutated K-RAS in the tissue. 26/35 (74%) patients showed an identical K-RAS pattern in tissue and serum. No codon 12 K-RAS alterations were found in serum samples of 22 patients with benign gastrointestinal diseases. Elevated serum CEA levels were detected in 16 patients, four of whom also presented serum RAS mutations. Our results confirm that K-RAS mutations can be found in circulating DNA extracted from serum samples of patients with colorectal cancer and show that there is a correspondence between serum and tissue K-RAS patterns. PMID- 11192826 TI - Chemotherapy and angiogenesis in advanced cancer: vascular endothelial growth factor (VEGF) decline as predictor of disease control during taxol therapy in metastatic breast cancer. AB - Angiogenesis is essential for tumor growth. Since vascular endothelial growth factor (VEGF) represents the main angiogenic factor, the control of VEGF secretion could constitute the most important mechanism to achieve the inhibition of angiogenesis-related processes. High blood concentrations have been proven to correlate with poor prognosis in advanced cancer. In experimental conditions, chemotherapeutic agents such as taxol appeared to inhibit VEGF-induced angiogenesis, while at present there are no data about the influence of chemotherapy on VEGF secretion in cancer patients. This preliminary study was performed to evaluate the effect of taxol therapy on VEGF secretion in advanced cancer patients in relation to the clinical response. The study included 14 patients with metastatic breast cancer who were treated with taxol monochemotherapy (175 mg/m2 i.v. every 21 days for three cycles). Serum levels of VEGF were measured by ELISA in blood samples collected before therapy and at 21 day intervals. The clinical response consisted of partial response (PR) in three and stable disease (SD) in six patients, whereas the other five patients had progressive disease (PD). Abnormally high pre-treatment levels of VEGF were seen in 8/14 patients. VEGF mean values significantly decreased during taxol therapy in patients with PR or SD, whereas no decline was observed in patients with PD. Moreover, the percent of normalization or decline greater than 50% in VEGF levels was significantly higher in patients with PR or SD than in those with PD (5/9 vs. 0/5). This preliminary study would suggest that the efficacy of taxol therapy in metastatic breast cancer - at least in terms of disease stabilization - may be associated with a decrease in VEGF blood levels followed by potential inhibition of cancer-related neovascularization. PMID- 11192827 TI - Two novel monoclonal antibodies against the MUC4 tandem repeat reacting with an antigen overexpressed by lung cancer. AB - In this study we investigated the immunochemical and cytochemical reactivity of two monoclonal antibodies against the 16-amino acid tandem repeat of MUC4 to demonstrate a possible variation of the mucin core peptide expression related to lung cancer. The immunocytochemical anti-MUC4 reactivity was analyzed in four lung cancer cell lines (Calu-1, Calu-3, H460, SKMES) and in other tumor cell lines, as well as in frozen materials from 21 lung adenocarcinomas (ACs), including five bronchioloalveolar carcinomas (BACs), and 11 squamous cell lung carcinomas (SqCCs). A weak fluorescence anti-MUC4 positivity (range: 10.3-16.2) was observed only in acetone-fixed lung cancer cell lines Calu-1, Calu-3 and H460. These three lung cancer cell lines also showed a cytoplasmic immunoperoxidase reactivity. The immunostaining in lung cancer tissues showed a granular cytoplasmic reactivity: 15/21 (71%) and 17/21 (80%) ACs were positive with BC-LuC18.2 and BC-LuCF12, respectively. All BACs were positive. Moderate to strong reactivity was present in well-differentiated ACs. In the normal lung parenchyma counterparts weak reactivity was found only in bronchiolar cells. All SqCCs were negative. Anti-MUC4 reactivity was also observed in the alveolar mucus. In conclusion, our anti-MUC4 MAbs detect a secretion product present in mucus and this product is elaborated by lung cancer cells and overexpressed in well-differentiated lung ACs. PMID- 11192828 TI - Monitoring therapy by serum HER-2/neu. AB - We have evaluated the performance of the Bayer Immuno 1 serum HER-2/neu assay. The precision is excellent and varied between 1.7% and 2.1% at values of HER 2/neu ranging from 16.8 ng/mL to 108.6 ng/mL. In normal women who were followed on a monthly basis the average deviation was 6%. The concentration (mean +/- SD) in normal women was 8.7 +/- 3.2 ng/mL. There was no difference between pre and postmenopausal women. The normal/abnormal cutoff was defined as greater than 15 ng/mL. In normal women and those with benign disease the specificity varied between 95% and 100%. In women with breast cancer the sensitivity was 1.7% in stage I disease, 3.0% in stage II, 16.7 in stage III and 35.5% in stage IV. There were 56 elevations (14.7%) in the total group of 285 women with breast cancer. There was an excellent correlation with a microtitre plate method (r=0.9944). Longitudinal studies showed clearly that women who expressed HER-2/neu in their tissue had elevated serum levels and these levels reflected the clinical course of the patient. More extensive control studies are required to establish the role of HER-2/neu assays in the management of women with breast cancer. PMID- 11192829 TI - CA 15-3: a prognostic marker in breast cancer. AB - CA 15-3 (also known as MUC1) is the most widely used serum marker in breast cancer. MUC1 is a large transmembrane glycoprotein which is frequently overexpressed and aberrantly glycosylated in cancer. Physiologically, MUC1 appears to play a role in cell adhesion and the high levels present in cancer may be causally involved in metastasis. At present the main uses of CA 15-3 are in preclinically detecting recurrent breast cancer and monitoring the treatment of patients with advanced breast cancer. In a prospective study of 368 patients we show that patients with high preoperative levels of CA 15-3 (>30.4 U/mL) had a worse outcome than patients with low levels of the marker. In multivariate analysis CA 15-3 as a prognostic marker was independent of both tumor size and nodal status. Furthermore, in multivariate analysis the prognostic impact of CA 15-3 was stronger than that of tumor size and at least as strong as nodal status. CA 15-3 may thus be the first independent prognostic serum marker in breast cancer. PMID- 11192830 TI - Surrogate markers of tumoral angiogenesis. AB - BACKGROUND: Angiogenesis is a prerequisite for tumor growth and metastasis. Vascular cell adhesion molecule1 (VCAM-1) is expressed on endothelial cells as a result of vascular endothelial growth factor (VEGF) stimulation. PURPOSE: To determine if measurement in serum of VEGF or VCAM-1 provides an accurate measure of tumor angiogenesis. METHODS: VCAM-1 and VEGF were measured in the serum of women with early and advanced breast cancer by ELISA. Levels were compared to levels of VCAM-1 and VEGF in women with normal breasts and levels of the endothelial glycoprotein von Willebrand factor. Levels of VEGF and VCAM-1 in women with early breast cancer were correlated with established clinicopathological prognostic markers and intratumoral microvessel density (IMD). RESULTS: In early breast cancer serum VCAM-1 correlated closely with the microvessel density in tumors (r=0.61, p<0.001). Women with lymph node-positive and high-grade tumors had higher levels of serum VCAM-1 than women with lymph node-negative and low-grade tumors. Serum VEGF demonstrated no correlation with established prognostic features or IMD. Levels of VCAM-1 and VEGF were raised in women with advanced breast cancer. CONCLUSION: Serum VCAM-1 is a surrogate marker of angiogenesis in breast cancer and its measurement may help in the assessment of antiangiogenic drugs currently in phase II trials. PMID- 11192831 TI - The prognostic value of the tumor marker CA 15-3 at initial diagnosis of patients with breast cancer. AB - CA 15-3 has been most widely used as a serum tumor marker in follow-up and detection of breast cancer recurrence. In this study we have specifically focused upon the prognostic implications and utility of preoperative CA 15-3 levels. We have identified on our database 414 patients with breast cancer in whom serial levels of the serum tumor marker CA 15-3 had been determined at diagnosis and follow-up. We have analyzed the follow-up and clinical outcomes in these patients and from this data we have assessed the potential of CA 15-3 as a predictor of five-year overall and disease-free survival. Our results show that an initially elevated CA 15-3 level is associated with a very poor prognosis in both early and late stage disease. Elevated pre-biopsy CA 15-3 levels are associated with 14% five-year disease-free survival rates and 17% overall survival rates at five years. In contrast, normal CA 15-3 levels are associated with 47% five-year disease-free survival rates and 54% overall survival rates at five years (p<0.01). Comparison of five-year survival rates between patients with elevated and normal CA 15-3 levels in early breast cancer (stage I and II) also showed significant differences, with survival being 41% and 75%, respectively (p<0.01). PMID- 11192832 TI - Human MUC1 mucin: a multifaceted glycoprotein. AB - Human MUC1 mucin, a membrane-bound glycoprotein, is a major component of the ductal cell surface of normal glandular cells. MUC1 is overexpressed and aberrantly glycosylated in carcinoma cells. The role MUC1 plays in cancer progression represents two sides of one coin: on the one hand, loss of polarity and overexpression of MUC1 in cancer cells interferes with cell adhesion and shields the tumor cell from immune recognition by the cellular arm of the immune system, thus favoring metastases; on the other hand, MUC1, in essence a self antigen, is displaced and altered in malignancy and induces immune responses. Tumor-associated MUC1 has short carbohydrate sidechains and exposed epitopes on its peptide core; it gains access to the circulation and comes into contact with the immune system provoking humoral and cellular immune responses. Natural antibodies to MUC1 present in the circulation of cancer patients may be beneficial to the patient by restricting tumor growth and dissemination: early stage breast cancer patients with a humoral response to MUC1 have a better disease-specific survival. Several MUC1 peptide vaccines, differing in vectors, carrier proteins and adjuvants, have been tested in phase I clinical trials. They are capable of inducing predominantly humoral responses to the antigen, but evidence that these immune responses may be effective against the tumor in humans is still scarce. PMID- 11192833 TI - Treatment of trichiasis with argon laser. AB - PURPOSE: In this prospective study, argon laser photocoagulation was used to eliminate misdirected cilia. The cases were followed up to see the results and recurrences with this treatment. METHODS: 60 eyelids of 45 patients with trichiasis were treated with the argon laser. After topical anesthesia a blue green argon laser was used with 1 watt power, for 0.20 seconds, with 100 micrometer beam diameter. The beam was directed coaxially to the lash follicle to create a 2-3 mm crater and vaporization was observed. After crater formation, the laser parameters were changed to 1.2 watt power, for 0.20 seconds, with 200 micrometer beam diameter, to destroy residual follicular tissue. Up to five lashes were treated in one session. At the end of each session an antibiotic ointment was used t.i.d. for a week. RESULTS: Patients have been followed for 4 12 months (mean 6 months). Recurrences have been seen in 15 of 60 eyelids (25%). Laser treatment has been used with the same protocol for the cases with recurrence and results have been successful in eight of them. Postoperatively severe pain, hemorrhage, scar formation, neovascularization of lid margin, or infection were not seen in any patient. In three cases mild hypopigmentation and in three other cases mild lid notching were observed. CONCLUSIONS: Argon laser lash ablation can be done as an effective office procedure with topical anesthesia. The advantages include low recurrence and complication rates in carefully selected patients and minimal postoperative discomfort. PMID- 11192834 TI - The control of matrix metalloproteinase-2 expression in normal and keratoconic corneal keratocyte cultures. AB - PURPOSE: Early phase keratoconic corneas and their cultured keratocytes abnormally produce the Mr 62,000 form of the matrix metalloproteinase-2 (MMP-2). It is known that platelet derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) are involved in the regulation of MMP activity and tissue inhibitor of metalloproteinase (TIMP) production in non-ocular tissues. The purpose of this enquiry was to determine whether these growth factors also play a role in the activity and/or production of corneal MMP-2 and TIMP, and whether their activity could account for the existence of the Mr 62,000 form of MMP-2 in keratoconic corneas. METHODS: Confluent cultures of normal and early-phase keratoconic corneal keratocytes were established and incubated in serum-free media in the presence or absence of PDGF and TGF-beta. The proteins secreted by these cells over periods of 7 days were harvested for analysis. The total protein produced was determined spectrophotometrically. MMP-2 was visualised by SDS gelatin polyacrylamide gel electrophoresis and assayed using radiolabelled type IV collagen as substrate. The enzyme inhibitors, TIMP-1 and TIMP-2, were quantified by dot blot immunoassay. RESULTS: The addition of PDGF or TGF-beta to the culture medium of keratoconic corneal keratocytes had no significant effect on overall protein production, MMP-2 activity or on the amounts of TIMP- 1 and TIMP-2 secreted. These observations also applied to normal corneal keratocytes, with the exception that PDGF induced expression of the Mr 62,000 species of MMP 2. CONCLUSIONS: PDGF may be involved in the production of the Mr 62,000 species of MMP-2 that is abnormally produced by early-phase keratoconic corneal keratocytes. PMID- 11192835 TI - Preoperative gentamicin eye drops and chlorhexidine solution in cataract surgery. Experimental and clinical results. AB - PURPOSE: 1) To evaluate the effects on the conjunctival flora of gentamicin ophthalmic eye drops 0.3%, given four times in 45 minutes, and a conjunctival rinse with 10 ml chlorhexidine 0.05% solution. 2) To investigate retrospectively the rate of endophthalmitis after cataract operations when these antimicrobials were applied preoperatively. METHODS: Seventy-six patients undergoing standard phacoemulsification operations were enrolled in the experimental part of the study. Cultures were taken preoperatively, 5 minutes after prophylaxis with either chlorhexidine or gentamicin. To assess the combined effects of chlorhexidine and gentamicin, cultures were taken after the cataract operation. Hospital charts were reviewed for cases of endophthalmitis in 1994 and 1995, when this prophylactic protocol was used at the St Erik's cataract surgery department. RESULTS: The conjunctival microflora was significantly suppressed by chlorhexidine rinsing alone (p = 0.001), while no other significant anti bacterial effects were observed with the experimental prophylaxis. The endophthalmitis rate was 32/12. 806 operations (0.25%). CONCLUSIONS: Topical rinsing with chlorhexidine solution suppresses conjunctival flora in the short term. Combined topical chlorhexidine and gentamicin prophylaxis does not eliminate postoperative endophthalmitis caused by gram-positive bacteria. PMID- 11192836 TI - Surgical approach in terson syndrome: vitreous and retinal findings. AB - PURPOSE: To report some interesting findings in patients with bilateral Terson syndrome. METHODS: We describe six eyes from three patients with Terson syndrome. Pars plana vitrectomy was performed in one eye twelve weeks, and in four eyes six months after the acute event. In one eye blood was suddenly spontaneously absorbed after four months. RESULTS: The four eyes operated six months after injury showed severe complications and final visual acuity was between light perception and 0.6. The eye with surgical attendance twelve weeks after the acute injury had an uneventful course, and final visual acuity was 0.7. CONCLUSIONS: Because of severe ocular complications and with a view to early rehabilitation, vitrectomy has been recommended for eyes with bilateral Terson syndrome, without spontaneous blood resorption. Surgery should be performed in at least one eye not later than four to eight weeks after the acute injury. PMID- 11192837 TI - Macular translocation: histopathologic findings in swine eyes. AB - PURPOSE: Macular translocation has been proposed as an alternative technique in the treatment of some cases of choroidal neovascularization. The purpose of the paper is to report the histopathologic findings in the retina of swine eyes undergone macular translocation. METHODS: Ten eyes of ten Yucatan pigs underwent posterior pars plana vitrectomy and scleral imbrication to achieve macular translocation. Mattress sutures were preplaced at the equator of the eyes. After a pars plana vitrectomy, balanced saline solution was injected under the temporal retina to produce a retinal detachment. Scleral imbrication was achieved by tightening the mattress sutures. An air-fluid exchange was performed and the eye was filled with sulfur hexafluoride 18%. The eyes were enucleated 2, 4, 8 and 12 weeks after surgery and analyzed under light and electron microscopy. RESULTS: Macular translocation was achieved in all cases. The major findings consist of a minimal decrease in the number of photoreceptors outer segments; also a change in the morphology was noted. This included some degree of loss of vertical alignment and an increase in the interphotoreceptor space. There was a recovery in the morphology of the photoreceptors over time. CONCLUSIONS: Minimal changes in the photoreceptors and retinal pigment epithelium are observed when macular translocation is performed with recovery of these changes over time. Scleral imbrication is an effective technique to achieve translocation of the fovea. PMID- 11192838 TI - Visual outcome and prognostic factors after vitrectomy for posterior segment foreign bodies. AB - PURPOSE: To identify the prognostic factors that predict final visual outcome in eyes with posterior segment intraocular foreign body (IOFB) injuries managed by primary pars plana vitrectomy. METHODS: Ninety-six consecutive patients with posterior segment IOFB injuries were retrospectively reviewed. Factors analyzed included initial visual acuity (VA), time between injury and presentation, site of entrance wound, uveal prolapse, vitreous prolapse, traumatized iris, endophthalmitis, location and size of IOFB, use of scleral buckling and/or an encircling band, gas tamponade, lensectomy, number of surgical procedures, and development of retinal detachment. Data were analyzed using univariate and multivariate logistic regression analysis. RESULTS: After a mean follow-up of 8.6 months, 63 eyes (65.6%) achieved VA of 20/200 or better, and 9 eyes (9.4%) had total retinal detachment complicated by inoperable proliferative vitreoretinopathy. On univariate analysis, predictors of poor vision (hand movements or less) were poor initial VA, corneoscleral entrance wound, uveal prolapse, vitreous prolapse, traumatized iris, and development of retinal detachment. In contrast, predictors of good visual outcome (20/200 or better) were absence of uveal prolapse, no endophthalmitis, and no retinal detachment. Multivariate analysis identified corneoscleral entrance wound, uveal prolapse, and development of retinal detachment as the only factors significantly associated with poor visual outcome. Absence of uveal prolapse was the only factor significantly associated with good visual outcome. CONCLUSIONS: Final visual outcome is greatly determined by the severity of the primary injury. On multivariate analysis, significant predictive factors of final VA were corneoscleral entrance wound, presence or absence of uveal prolapse, and development of retinal detachment. PMID- 11192839 TI - Immunohistochemical demonstration of metallothionein in eyes with choroidal melanomas. AB - PURPOSE: The since immunohistochemically detectable metallothionein (MT) overexpression has been described in a variety of human tumours, including skin melanomas, in relation to different stages of tumour development and progression. MATERIALS AND METHODS: We used a monoclonal antibody to investigate the distribution of MT in 18 formalin-fixed, paraffin-embedded, surgically enucleated eyes with choroidal melanomas, from 18 patients (8 male, 10 female; age range 30 83 years, mean 58.7). Clinico-pathological details and follow-up data (2-124 months, mean 36.1) were also available. MT immunoreactivity was recorded and the percentage of stained cells was graded for semiquantitative purposes. Correlations between immunohistochemical data and morphological characteristics of melanomas were investigated using non-parametric methods; survival analysis was done by the Kaplan-Meier method and the survival curves were compared by the Mantel-Cox log-rank test. RESULTS: MT immunoexpression was found in 15/18 cases (83.3%) with staining scores from 1 to 3; MT staining varied in intensity and was mainly localized in the cytoplasm, although a combined nuclear/cytoplasmic reactive pattern was seen in neoplastic elements. No differences in MT immunostaining were seen in relation to age or sex, tumour size, histotype and amount of pigment; univariate analysis of survival data showed no prognostic significance regarding MT expression. CONCLUSIONS: The immunohistochemical evidence of MT in neoplastic elements could be related to the production of this scavenging protein in the tumour for cell defense mechanisms against hydroxyl free radicals, and to act as a Zn donor, since Zn is required for the synthesis of DNA and DNA-repair enzymes. PMID- 11192840 TI - Alterations in antithrombin III activity and other blood coagulation parameters after retinal detachment surgery. AB - PURPOSE: To evaluate perioperative changes in blood coagulation in patients undergoing retinal detachment surgery. MATERIALS: Prospective study of 56 patients, aged from 19 to 82 (mean +/- S.D. 53 +/- 16.8) years, undergoing retinal detachment surgery (encirclement with scleral buckling) under general anesthesia. Excluded were patients with venous or arterial disease and any other factors that could affect the parameters under consideration. METHODS: Blood was sampled from the cubital vein one day before surgery, immediately after induction of anesthesia but before surgery, immediately after completion of the operation but before the termination of anesthesia and on days 1 and 4 after the operation. We measured antithrombin III activity (AT III), platelet count, fibrinogen concentration, activated partial thromboplastin time (aPTT) and prothrombin time (PT). RESULTS: Intraoperative AT III activity and platelet count were significantly lower, aPTT was shortened and PT prolonged, although all values remained within the normal range. These results indicate moderate activation of coagulation during retinal detachment surgery. On the first postoperative day coagulation activity was reduced, with increases in AT III activity, fibrinogen concentration and platelet count and prolongation of aPTT. CONCLUSIONS: During retinal detachment surgery there is moderate activation of coagulation in the systemic circulation. PMID- 11192841 TI - Systematic, combined treatment approach to nasolacrimal duct obstruction in different age groups. AB - PURPOSE: To report the outcome of a step-by-step treatment approach for congenital nasolacrimal duct obstruction (CNDO). METHODS: Three-hundred and fifty eyes with CNDO were included in the study. A number of treatment methods were applied systematically until a successful outcome was achieved. Listed in order from simple to more complex, the following methods were used: conservative management (massage and topical antibiotics), high-pressure syringing, probing, and silicone intubation. Treatment efficacy was determined according to age (Group 1: 0-6 months, Group 2: 7-12 months, Group 3: 13-24 months, Group 4: 25-72 months) and success rates were compared. RESULTS: Conservative management was applied only in children less than 1 year of age, and was successful in 91.8% of Group 1 and 60% of Group 2 eyes. The difference between these two success rates was significant (p = 0.003). High-pressure syringing was performed in children under 24 months of age, with success rates of 41.7% in Group 1, 33.3% in Group 2, and 12.5% in Group 3. The overall success rate for first probing in all groups was 76.1%, with a range of 69.4% to 80.9%. After second probing, the overall cure rate for the entire cohort was 88.0%, with a range of 74.9% to 94.8%. There was no real difference in probing cure rates relative to age (p > 0.05). Silicone intubation was indicated and performed in two eyes of Group 2 children, three eyes of Group 3, and nine eyes of Group 4. Two ducts in Group 4 eyes remained obstructed after silicone intubation. CONCLUSIONS: The systematic treatment approach to CNDO, including conservative management and minimally invasive procedures such as high-pressure syringing, probing, and silicone intubation, is highly successful. In this study, the cure rate for this combined approach was 100% in youngsters under 2 years of age and 94.5% in children 2 to 6 years old. PMID- 11192842 TI - Merkel cell carcinoma of the eyebrow extending into the orbit. AB - BACKGROUND: Merkel cell carcinoma is a rare and aggressive cutaneous neoplasm with high local recurrence and metastatic rates. PURPOSE: To highlight an unusual presentation of a Merkel cell carcinoma. CASE REPORT: We report a large Merkel cell tumor in an 85-year-old woman. It extended from the eyebrow into the upper nasal orbit posterior to the equator of the eye globe. Local resection resulted in microscopically complete removal of the tumor. During follow-up (20 months) no local recurrence was noticed but there was a metastasis in a lymphatic nodule. CONCLUSIONS: Merkel cell carcinoma often presents in the eyelids and periorbital region. However, extension from the eyebrow deep into the orbit is unusual. PMID- 11192843 TI - Ibopamine treatment in chronic hypotony secondary to long-lasting uveitis. A case report. AB - PURPOSE: To assess the clinical efficacy of ibopamine eye drops in severe hypotony secondary to chronic progressive uveitis. METHODS: Case report. A 47 year-old man with a 37-year history of diffuse uveitis and severe refractory hypotony was treated with topical 2% ibopamine (Trazyl) six times a day. Intraocular pressure, visual acuity, visual field and side effects were recorded during 15 months of follow-up. RESULTS: IOP, visual acuity and visual field increased after four days of therapy and lasted for two months when the drug was suspended because of the onset of filamentous keratopathy. A new course of treatment with 2% ibopamine eye drops in a different solvent (BSS) resulted in a stable increase in IOP, VA and visual field, with no side effects in a follow-up of 13 months. CONCLUSIONS: Ibopamine 2% eye drops in BSS solvent seem effective in the treatment of uveitis-related hypotony. PMID- 11192844 TI - Magnetic resonance imaging in cavitary choroidal melanoma. AB - PURPOSE: To report the development of a cavitary choroidal melanoma in a patient with nevus of Ota and describe its magnetic resonance imaging (MRI) features. PATIENT: A 66-year-old man with right oculodermal melanocytosis and an ipsilateral choroidal cavitary melanoma was seen. Diagnosis was suspected on the clinical, ultrasonographic and MRI findings. RESULTS: T1-weighted image showed a hyperintense solid mass containing hypointense cystic-like spaces delineated by hyperintense septa with respect to the vitreous. The reverse image was observed on T2-weighted images. A choroidal melanoma comprising epithelioid and spindle cells with multilocular cavities was documented histopathologically. CONCLUSIONS: There may be an association between cavitary melanoma and nevus of Ota. Characteristic MRI findings could be helpful in the differential diagnosis of cavitary uveal melanoma. PMID- 11192845 TI - Birdshot retinochoroidopathy: measurement of the posterior fundus spots and macular edema using a retinal thickness analyzer, before and after treatment. AB - PURPOSE: To measure the retinal thickness in the macular area and at the typical fundus spots in a patient with birdshot retinochoroidopathy, using the retinal thickness analyzer (RTA), a new image analyzer involving laser-slit biomicroscopy, and to quantify the changes after systemic corticosteroid therapy. CASE REPORT: A 54-year-old man with posterior uveitis underwent visual acuity measurement, fluorescein and indocyanine green (ICG) angiographies, optical coherence tomography (OCT) and RTA measurements before and after steroid treatment. RESULTS: The thickness at the birdshot spots measured with RTA remained unchanged after treatment, but the thickness at the fovea decreased in both eyes. Fluorescein and ICG angiographies and OCT showed no change with treatment. CONCLUSIONS: RTA seems a more sensitive method for assessing changes in macula thickness in the course of birdshot retinochoroidopathy and can help document the effect of treatment. PMID- 11192846 TI - Bilateral anterior ischaemic optic neuropathy due to optic disc drusen. AB - PURPOSE: To report a case of bilateral anterior ischaemic optic neuropathy due to buried optic disc drusen. METHODS: Case report. RESULTS: A 64-year-old man presented with swollen optic discs and features suggestive of anterior ischaemic optic neuropathy (AION) in the left and right eye on two separate occasions ten months apart. Detailed ocular examination at presentation and systemic investigations did not reveal an underlying cause for the AION. At a later follow up, optic disc drusen were noted in both eyes as partial optic atrophy had set in. This was confirmed by ultrasound B scan and demonstration of autofluorescence. CONCLUSIONS: In patients presenting with AION uncommon underlying causes must be considered. Routine ultrasound B scan at presentation can easily establish or exclude optic disc drusen as an underlying cause. PMID- 11192848 TI - SIBioC 2000. 32nd National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology. Rimini, Italy, 12-15 September 2000. Abstracts. PMID- 11192847 TI - Anterior segment ischemia and retinal detachment after vertical rectus muscle surgery. PMID- 11192849 TI - T-helper cell responses to HIV envelope peptides in cord blood: protection against intrapartum and breast-feeding transmission. AB - BACKGROUND: Acquired HIV-specific cell-mediated immune responses have been observed in exposed-uninfected individuals, and it has been inferred, but not demonstrated, that these responses constitute a part of natural protective immunity to HIV. This inference was tested prospectively in the natural exposure setting of maternal-infant HIV transmission in a predominantly breast-fed population. METHODS: Cord blood from infants of HIV-seropositive women in Durban, South Africa, were tested for in vitro reactivity to a cocktail of HIV envelope peptides (Env) using a bioassay measuring interleukin-2 production in a murine cell line. Infants were followed with repeat HIV RNA tests up to 18 months of age to establish which ones acquired HIV-infection. RESULTS: T-helper cell responses to Env were detected in 33 out of 86 (38%) cord blood samples from infants of HIV seropositive women and in none of nine samples from seronegative women (P = 0.02). Among infants of HIV-seropositive mothers, three out of 33 with T-helper responses to Env were already infected before delivery (HIV RNA positive on the day of birth), two were lost to follow-up, and none of the others (out of 28) were found to be HIV infected on subsequent tests. In comparison, six out of 53 infants unresponsive to Env were infected before delivery, and eight out of 47 (17%) of the others were found to have acquired HIV infection intrapartum or post partum through breast-feeding (P = 0.02). CONCLUSIONS: T-helper cell responses to HIV envelope peptides were detected in more than one-third of newborns of HIV infected women; no new infections were acquired by these infants at the time of delivery or post-natally through breast-feeding if these T-helper cell responses were detected in cord blood. PMID- 11192850 TI - Treatment of cervicitis is associated with decreased cervical shedding of HIV-1. AB - OBJECTIVE: To determine whether cervical mucosal shedding of HIV-1 RNA and HIV-1 infected cells decreases following successful treatment of cervicitis. DESIGN: Prospective interventional study. SETTING: Sexually Transmitted Infections Clinic, Coast Provincial General Hospital, Mombasa, Kenya. PARTICIPANTS: Thirty six HIV-1 seropositive women with cervicitis: 16 with Neisseria gonorrhoeae, seven with Chlamydia trachomatis, and 13 with non-specific cervicitis. INTERVENTIONS: Treatment of cervicitis. MAIN OUTCOME MEASURES: Levels of total (cell-free and cell-associated) HIV-1 RNA and presence of HIV-1 DNA (a marker for infected cells) in cervical secretions before and after resolution of cervicitis. RESULTS: After treatment of cervicitis, the median HIV-1 RNA concentration in cervical secretions was reduced from 4.05 to 3.24 log10 copies/swab (P = 0.001). Significant decreases in cervical HIV-1 RNA occurred in the subgroups with N. gonorrhoeae (3.94 to 3.28 log10 copies/swab; P = 0.02) and C. trachomatis (4.21 to 3.19 log10 copies/swab; P = 0.02). Overall, the prevalence of HIV-1 infected cells in cervical secretions also decreased after treatment, from 67% to 42% (odds ratio, 2.8; 95% confidence interval, 1.3-6.0; P = 0.009). Detection of infected cells was associated with higher mean HIV-1 RNA levels (4.04 versus 2.99 log10 copies/swab; P< 0.0001). CONCLUSIONS: Effective treatment of cervicitis resulted in significant decreases in shedding of HIV-1 virus and infected cells in cervical secretions. Treatment of sexually transmitted diseases may be an important means of decreasing the infectivity of HIV-1 seropositive women by reducing exposure to HIV-1 in genital secretions. PMID- 11192851 TI - Changes in host cell molecules acquired by circulating HIV-1 in patients treated with highly active antiretroviral therapy and interleukin-2. AB - OBJECTIVE: To analyse cell membrane proteins (CMP) acquired by HIV-1 present in the plasma of asymptomatic patients, and their modifications after a cycle of highly active antiretroviral therapy (HAART) and interleukin (IL)-2. DESIGN AND METHODS: Plasma samples from eight drug-naive asymptomatic subjects underwent immobilized antibody capture (IAC) to detect CMP on the surface of circulating HIV-1. The CMP considered were lymphocyte subset markers (CD45RA, CD45RO), activation markers (HLA-DR), adhesion molecules (LFA-3), costimulatory proteins (B7-2), lymph-node homing receptors (CD62L) and pro-apoptosis molecules (FasL). This analysis was repeated after one cycle of HAART + IL-2, after virus rebound. RESULTS: LFA-3, followed by CD45RO and HLA-DR, are the most represented CMP on the surface of circulating virions in naive asymptomatic patients; CD45RA, CD62L, B7-2 and FasL are detected only occasionally. After rebound, a significant reduction of CD45RO and HLA-DR, but not of LFA-3, is observed on virions, whereas CD45RA and CD62L, as well as other molecules, are not affected, remaining almost undetectable. CONCLUSIONS: Assuming that CMP on HIV-1 reflect the cellular origin of virions, activated T cells expressing CD45RO, HLA-DR, and LFA-3 may be the main source of HIV-1 in asymptomatic patients. After a cycle of HAART + IL-2, followed by therapy interruption, CD45RA and CD62L are detected on virions rarely, indicating that even during virus rebound, expanded naive T cells do not become a major target of virus replication. Furthermore, the presence of HLA-DR on rebound HIV-1 is decreased, consistent with decreased activation of the HIV producing cells. More extensive investigation may clarify the significance of these findings with respect to pathogenesis. PMID- 11192852 TI - Effect of computer-assisted self-interviews on reporting of sexual HIV risk behaviours in a general population sample: a methodological experiment. AB - OBJECTIVES: To develop methods to maximize the accuracy of reporting HIV risk behaviours in a general population survey. We assessed the feasibility of using a computer-assisted self-completion interview (CASI) in comparison with pen-and paper self-completion interview (PAPI). DESIGN: A probability sample survey of residents aged 16-44 years in Britain, with alternate assignment of addresses to interview by CASI (462) or PAPI (439). METHODS: Personal interviews exploring demographic and sexual behaviour variables. Principal outcome measures were the impact of CASI in relation to PAPI on data quality and rates of reporting a range of behaviours. RESULTS: A total of 901 interviews were completed; 829 individuals were eligible for and accepted the self-completion module. Internal consistency of data items was greater with CASI than PAPI and item non-response was lower. Overall, there was no significant difference in rates of reporting between CASI and PAPI. The main effect for CASI compared with PAPI in a generalized estimating equation (GEE) analysis was an OR (95% CI) of 1.04 (0.92-1.17). Variables were also examined individually, including homosexual partnership (adjusted OR 1.26 95%, CI 0.69-2.29), payment for sex (adjusted OR 0.68 95% CI 0.29-1.59), masturbation (adjusted OR 0.89 95% CI 0.66 1.22) and five or more partners in the past 5 years (OR 0.85 95% CI 0.61 -1.19). CONCLUSION: We found no evidence of a consistent effect of CASI on rates of reporting sexual HIV risk behaviours in this sample. CASI resulted in improvement in internal consistency and a reduction in missed questions. PMID- 11192853 TI - Reassessing the goal of antiretroviral therapy in the heavily pre-treated HIV infected patient. PMID- 11192854 TI - Cross-staining of cytotoxic T lymphocyte populations with peptide-MHC class I multimers of natural HIV-1 variant antigens. PMID- 11192855 TI - Enteric microtubule depolymerization in HIV infection: a possible cause of HIV associated enteropathy. PMID- 11192856 TI - HIV resistance assay results and their effect on therapeutic decisions. PMID- 11192857 TI - Efavirenz-associated breast hypertrophy in HIV-infection patients. PMID- 11192858 TI - The ADAM study continued: maintenance therapy after 50 weeks of induction therapy. PMID- 11192859 TI - Predictors of progression in chronically infected naive patients with plasma viraemia below 5000 copies/ml and CD4 T lymphocytes greater than 500 x 10(6)/I. PMID- 11192860 TI - Absence of an effect of herpes simplex virus type 2 infection on HIV disease progression: data from a cohort of HIV-positive individuals with known date of seroconversion. PMID- 11192861 TI - Pathological fractures in AIDS patients with osteopenia and osteoporosis induced by antiretroviral therapy. PMID- 11192862 TI - Alopecia universalis and Graves' disease in the setting of immune restoration after highly active antiretroviral therapy. PMID- 11192863 TI - Renal tubular acidosis and hypophosphataemia after treatment with nucleoside reverse transcriptase inhibitors. PMID- 11192864 TI - Monocytes harbour replication-competent, non-latent HIV-1 in patients on highly active antiretroviral therapy. AB - OBJECTIVE: To determine whether HIV-1 can be recovered from blood monocytes as well as resting, memory CD4 T lymphocytes of patients on highly active antiretroviral therapy (HAART) with undetectable plasma viraemia and whether infection is active or latent. DESIGN: Five patients with plasma HIV-1-RNA levels of less than 500 copies/ml for at least 3 months and less than 50 copies/ml at the time of sampling were initially selected, followed by an additional five patients with viral loads of less than 50 copies/ml for 3 months or more. METHODS: Monocytes were isolated from blood by plastic adherence, then further purified by a second adherence step or CD3 depletion before co-culture with CD8 depleted donor peripheral blood mononuclear cells. Virus isolates were examined for mutations conferring resistance to reverse transcriptase or protease inhibitors and for genotype. The highly purified monocytes were also analysed for the presence of proviral and unintegrated viral DNA and multiply spliced (MS) viral mRNA by polymerase chain reaction. RESULTS: Virus was recovered from monocytes of five patients. Sequencing of the recovered viruses did not reveal multiple drug resistance, and was consistent with a non-syncytium-inducing/CCR5 phenotype. Proviral DNA was detectable in monocytes from all subjects, and unintegrated HIV-1 DNA and MS RNA was found in four out of five populations examined. CONCLUSION: Recovery of replication-competent virus from some HAART patients indicates that monocytes can also harbour HIV-1. Detection of circular, viral DNA and spliced RNA, albeit at very low levels, in these cells suggests that their infection is recent and transcriptionally active rather than latent. PMID- 11192865 TI - Discontinuation of maintenance therapy for cytomegalovirus retinitis in HIV infected patients receiving highly active antiretroviral therapy. AB - OBJECTIVE: To study the safety of discontinuing cytomegalovirus (CMV) maintenance therapy among patients with cured CMV retinitis receiving highly active antiretroviral therapy (HAART). METHODS: Patients with a history of CMV retinitis who were receiving anti-CMV maintenance therapy and who had a CD4 cell count > 75 x 10(6) cells/l and a plasma HIV RNA level < 30000 copies/ml while on HAART were included in a multicentre prospective study. Maintenance therapy for CMV retinitis was discontinued at enrolment and all the patients were monitored for 48 weeks by ophthalmological examinations and by determination of CMV markers, CD4 cell counts and plasma HIV RNA levels. T helper-1 anti-CMV responses were assessed in a subgroup of patients. The primary study endpoint was recurrence of CMV disease. RESULTS: At entry, the 48 assessable patients had been taking HAART for a median of 18 months. The median CD4 cell count was 239 x 10(6) cells/l and the median HIV RNA load was 213 copies/ml. Over the 48 weeks, 2 of the 48 patients had a recurrence of CMV disease. The cumulative probability of CMV retinitis relapse was 2.2% at week 48 (95% confidence interval, 0.4-11.3) and that of all forms of CMV disease 4.2%. CMV blood markers remained negative throughout follow-up. The proportion of patients with CMV-specific CD4 T cell reactivity was 46% at baseline and 64% at week 48. CONCLUSIONS: CMV retinitis maintenance therapy may be safely discontinued in patients with CD4 cell counts above 75 x 10(6) cells/l who have been taking HAART for at least 18 months. PMID- 11192866 TI - Phase I/II dose escalation and randomized withdrawal study with add-on azodicarbonamide in patients failing on current antiretroviral therapy. AB - BACKGROUND: Azodicarbonamide (ADA), a HIV-1 zinc finger inhibitor, targets a new step in viral replication and cell infectivity. OBJECTIVE: A first phase I/II clinical study of ADA. METHODS: ADA was administered at escalating doses concomitantly with current antiviral therapy during a 3-month open-label period in patients with advanced AIDS and documented virological failure. After 3 months, patients were randomized in a double-blind placebo-controlled withdrawal, ADA being given at the highest tolerated dosage. RESULTS: Fifteen patients with advanced disease failing on combined antiretroviral therapy, 75% of them with proven phenotypic resistance, had a median baseline CD4 cell count of 85 x 10(6) cells/l, CD4/CD8 cell ratio of 0.09 and median plasma RNA viral load of 4.2 log10 copies/ml. Tolerance to ADA was dose dependent and some patients developed nephrolithiasis, glucose intolerance or showed an ADA-related cytotoxicity towards CD4 cells at higher dosages. No patient died during the study period. ADA increased CD4 cell percentage, increased the CD4/CD8 cell ratio and decreased plasma RNA viral load from baseline. At the end of the double-blind period, the ADA group, but not the placebo group, showed a significant response (P < 0.05). No phenotypic resistance to ADA was observed. Overall, 3/11 patients (27%) had consistent viral load reductions > 0.5 log10 copies/ml compared with baseline and 5/ 11 (45%) showed a CD4 cell recovery from baseline > 33%. In responders, ADA induced a median peak increase in CD4 cell percentage change from baseline of 65% (range 47-243%), and viral load decrease of 1.04 log10 copies/ml (range 0.52 1.23). CONCLUSIONS: The maximal tolerated dosage of ADA appears to be 2 g (three times daily). This study provides safety results that will allow larger clinical trials to confirm the preliminary efficacy data. PMID- 11192867 TI - The virological response to highly active antiretroviral therapy over the first 24 weeks of therapy according to the pre-therapy viral load and the weeks 4-8 viral load. AB - OBJECTIVES: To describe the viral response to HAART by weeks 4 and 8 in previously antiretroviral-naive patients. To assess whether the weeks 4 or 8 viral loads are useful predictors of viral suppression by week 24. DESIGN: A large clinical database including 453 antiretroviral-naive patients whose plasma viral load was monitored every 4 weeks. METHODS: Observed probabilities of achieving a viral load < or = 500 copies/ml by week 24 (days 84-168) from starting highly active antiretroviral therapy (HAART) were calculated according to viral loads at weeks 4 and 8. RESULTS: A total of 42.4% of patients (153/361) reached < or = 500 copies/ml viral load by week 4 and 70.4% (245/348) by week 8. Viral suppression below 500 copies/ml by 4-8 weeks was similar irrespective of the pre-HAART viral load. In patients with viral loads above 10000 copies/ml at week 4, 60.6% (20/33) achieved < or = 500 copies/ml by week 24. In patients with viral loads still above 10000 copies/ml at week 8, only 42.3% (11/26) achieved < or = 500 copies/ml by week 24, and only 33.3% (3/9) maintained viral suppression below 500 copies/ml to week 48. CONCLUSION: Viral loads at weeks 4 and 8 should be monitored to detect early signs of low subsequent viral suppression. For previously antiretroviral-naive patients whose viral loads after 8 weeks of HAART are still above 10000, there is an urgent need to assess adherence to therapy, drug levels and resistance, so management can be modified accordingly to reduce the rate of week 24 virological failure. PMID- 11192868 TI - Bacteremia due to Mycobacterium tuberculosis or M. bovis, Bacille Calmette-Guerin (BCG) among HIV- positive children and adults in Zambia. AB - BACKGROUND: Among adults with advanced HIV infection in developing countries, bacteremia due to Mycobacterium tuberculosis (MTB) is common and bacteremia due to M. bovis (bacille Calmette-Guerin; BCG) is rare. Comparable data are not available for children with HIV. OBJECTIVE: To compare the prevalence of bacteremia due to M. tuberculosis or M. bovis BCG in hospitalized children and adults with HIV infection in a developing country with a high prevalence of tuberculosis and HIV and > 95% BCG immunization coverage. DESIGN: Descriptive cross-sectional study. METHODS: Prospectively hospitalized patients in Lusaka, Zambia who were suspected to have HIV infection underwent phlebotomy for HIV ELISA, HIV viral load, and lysis-centrifugation blood culture for mycobacteria. Histories were obtained and patients were examined for BCG scars. Mycobacterial isolates were identified using DNA probes for MTB complex (MTBC), multiplex PCR and IS6110 typing. RESULTS: The median age of 387 HIV-positive children was 15 months; 98% were BCG immunized. The median age of 344 HIV-positive adults was 32 years; 44% were BCG immunized. Blood cultures were positive for mycobacteria in six children (2%) and 38 adults(11%) (P < 0.001). The six pediatric isolates included five MTBC (40% clustered) and one BCG. The 38 adult isolates included 36 MTBC (16% clustered) and two M. avium complex. CONCLUSION: Bacteremia due to MTB is less common among children than adults with advanced HIV infection in Zambia. Bacteremia due to M. bovis BCG is rare even among children with recent BCG immunization and symptomatic HIV infection. PMID- 11192869 TI - Multiple drug rescue therapy for HIV-infected individuals with prior virologic failure to multiple regimens. AB - OBJECTIVES: To characterize the antiviral response and tolerability of a multi drug rescue therapy (MDRT) among heavily pretreated patients. METHODS: Observational study conducted in a single, university-based tertiary referral clinic. Patients (n = 106) who failed several prior regimens started MDRT including at least five antiretroviral (ARV) drugs between August 1997 and June 1998. The most common starting regimen included three nucleoside reverse transcriptase inhibitors and two protease inhibitors, which was prescribed to 45 (42.5%) patients. Virologic response was defined as plasma viral load < 400 copies/ml on at least two consecutive visits. RESULTS: Median prior ARV exposure was seven drugs over a median time of 43 months. Fifty-nine percent of the patients were phenotypically (VIRCO Antivirogram) resistant at baseline to seven or more ARV. Median plasma viral load change following initiation of MDRT was 1.04 log10 copies/ml over a median of 15 months. Using intention-to-treat analysis 40% of patients had plasma viral load values < 400 copies/ml between weeks 47 and 57 of follow-up. Twenty-six patients (25%) experienced severe laboratory abnormalities or subjective adverse drug effects and six of these participants discontinued therapy. CONCLUSION: MDRT induced a substantial antiviral response in this heavily pretreated group of patients despite extensive phenotypic resistance at baseline. Adverse effects were frequent but generally manageable. Our data suggest that relying exclusively on historical, clinical and laboratory evidence may not be sufficient to rule out a possible antiviral response when multiple drug regimens are used in this heavily pretreated patient population. PMID- 11192870 TI - Efavirenz plasma levels can predict treatment failure and central nervous system side effects in HIV-1-infected patients. AB - OBJECTIVE: Limited information exists on the clinical usefulness of drug level monitoring for efavirenz, a once-daily non-nucleoside reverse transcriptase inhibitor (NNRTI). The aim of this study was to determine whether efavirenz plasma concentration monitoring could predict treatment failure and central nervous system (CNS) tolerability. METHODS: Blood samples were obtained from 130 HIV-infected patients receiving efavirenz in combination with other antiretroviral agents for more than 3 months. Efavirenz plasma concentrations were measured by high-performance liquid chromatography. An evaluation of CNS side-effects was performed and the viral load, CD4 cell count and other clinical and laboratory data were assessed. In 85 patients, these measures were repeated at 3 month intervals. RESULTS: Efavirenz plasma levels (n = 226) were measured at an average of 14 h after drug intake. Drug concentrations ranged from 125 to 15230 microg/l (median 2188). Large inter-patient (CV 118%) and limited intra patient (CV 30%) variabilities were observed in efavirenz levels. Virological failure was observed in 50% of patients with low efavirenz levels (< 1000 microg/l) versus 22 and 18% in patients with 1000-4000 microg/l or more than 4000 microg/l, respectively. CNS toxicity was approximately three times more frequent in patients with high efavirenz levels (> 4000 microg/l) compared with patients with 1000-4000 microg/l. CONCLUSION: Treatment failure and CNS side-effects are associated with low and high efavirenz plasma levels, respectively. The important inter-individual variability in efavirenz levels strongly argues for dose adjustment on the basis of therapeutic drug monitoring to optimize treatment. PMID- 11192871 TI - Understanding delay to medical care for HIV infection: the long-term non presenter. AB - OBJECTIVE: To examine delayed presentation for HIV testing and primary care in the second decade of the AIDS epidemic. DESIGN: Cohort study in two urban hospitals in the USA between February 1994 and April 1996. METHODS: A total of 203 consecutive outpatients on initial HIV primary care presentation were interviewed about sociodemographic characteristics, alcohol and drug use, social support, sexual practices, HIV testing, awareness of possible HIV infection, and CD4 cell count. MAIN OUTCOME MEASURE: Duration of delay to medical presentation in years based on CD4 cell count, factors independently associated with low CD4 cell counts, frequency of awareness of HIV risk before testing. RESULTS: The estimated mean duration between acquiring HIV infection and initial presentation to primary care was 8.1 years (95% CI 7.5, 8.6) based on our cohort's median initial CD4 cell count of 280/microl. Male sex, older age, and no jail time were associated with lower CD4 cell counts; 34% reported not being aware that they were at risk of HIV before testing. Heterosexual intercourse as a risk behavior for HIV was the most statistically significant factor for personal unawareness of HIV risk. Of those who acknowledged awareness, the mean time between awareness of HIV risk and testing was 2.5 years (median 1.0 year). CONCLUSION: In the pre highly active antiretroviral therapy era, HIV-infected patients frequently initiated primary medical care years after initial infection, at a time of advanced immunosuppression. Over one-third of HIV-infected patients were not cognisant of their HIV risk before testing, a condition significantly associated with heterosexual intercourse as the only HIV risk behavior. PMID- 11192872 TI - Factors associated with HIV-1 infection among sex workers of Addis Ababa, Ethiopia. AB - OBJECTIVE: To study the prevalence and risk factors for HIV infection among sex workers of Addis Ababa, Ethiopia. DESIGN AND METHODS: Cross-sectional survey on socio-demographic characteristics, behaviours, and HIV serological status of sex workers attending two health centres of Addis Ababa. RESULTS: HIV prevalence among sex workers was 274 of 372 (73.7%). Several factors were significantly associated with an increased risk of being HIV-infected [among others, working in 'shared rooms', high number of clients, use of injectable hormones, and positive Treponema pallidum particle agglutination (TPPA) serology], and others with a decreased risk (being born in Addis Ababa, high level of education, peer education on sex work, condom use, use of oral pill, and use of condoms for contraception). Of interest, sex workers who were using condoms for contraception were, compared with others, more likely to use condoms consistently (65 versus 24%, respectively; P < 0.001), and less likely to be HIV-infected (55 versus 86%, respectively; P < 0.001). In multivariate analysis [log-binomial model, giving estimates of the prevalence ratio (PR)], being born in Addis Ababa (PR = 0.74; 95% confidence interval (CI), 0.61-0.91), using condoms for contraception (PR = 0.73; 95% CI, 0.64-0.85), and a positive TPPA serology (PR = 1.21; 95% CI, 1.09 1.36), remained significantly associated with HIV infection. CONCLUSIONS: HIV prevalence was remarkably high among sex workers of Addis Ababa. Condom use was higher, and HIV prevalence lower, in sex workers using condoms not only for prevention of HIV and sexually transmitted diseases, but also for contraceptive purpose. This finding is of particular interest for its implications for prevention strategies among sex workers in the developing world. PMID- 11192873 TI - Trend in HIV-1 prevalence in an antenatal clinic in North Uganda and adjusted rates for the general female population. AB - OBJECTIVES: To estimate HIV-1 prevalence among women attending an antenatal clinic in the Gulu District (North Uganda) and, based on these data, among the district's female population. METHODS: Anonymous HIV-1 screening was performed for 8555 antenatal clinic attendees aged 15-39 years in the period 1993-1997. The results were used to estimate the prevalence among the district's female population, accounting for differences in fertility rates by HIV-1 serostatus. RESULTS: Among antenatal clinic attendees, HIV-1 prevalence showed a significant linear decrease (P < 0.001), from 26.0% in 1993 [95% confidence Interval (CI), 23.2-29.0%] to 16.1% in 1997 (95% CI, 14.8-17.5%). This decrease was mostly due to a marked decrease until 1995 (14.3%; 95% Cl, 12.7-16.0%) and was more pronounced among women aged under 30 years (P < 0.001), from both urban and rural areas (P < 0.001). The risk of being infected was higher among women from urban areas (Gulu Municipality), both over the entire period (adjusted prevalence proportion ratio = 1.54; 95% CI, 1.40-1.68) and by individual year. The estimated prevalence for the 15-39-year-old female population, standardized by age and area of residence, decreased from 25.4% in 1993-1994 to 17.8% in 1996-1997; these rates were 1.22 and 1.28 times higher, respectively, than those among antenatal clinic attendees. CONCLUSIONS: The trend of decrease among young women, for whom changes in HIV-1 prevalence more closely reflect incidence, could be partially due to a reduction in risk behaviour and a consequent decreasing incidence. Differences in fertility rates by HIV-1 serostatus should be addressed when using antenatal clinic data to estimate prevalence among the general female population. PMID- 11192874 TI - ABT-378/ritonavir plus stavudine and lamivudine for the treatment of antiretroviral-naive adults with HIV-1 infection: 48-week results. AB - OBJECTIVE: To evaluate the safety and antiviral activity of different dose levels of the HIV protease inhibitor ABT-378 combined with low-dose ritonavir, plus stavudine and lamivudine in antiretroviral-naive individuals. DESIGN: Prospective, randomized, double-blind, multicenter. METHODS: Eligible patients with plasma HIV-1 RNA > 5000 copies/ml received ABT-378 200 or 400 mg with ritonavir 100 mg every 12 h; after 3 weeks stavudine 40 mg and lamivudine 150 mg every 12 h were added (group I, n = 32). A second group initiated treatment with ABT-378 400 mg and ritonavir 100 or 200 mg plus stavudine and lamivudine every 12 h (group II, n = 68). RESULTS: Mean baseline HIV-1 RNA was 4.9 log10 copies/ml in both groups and CD4 cell count was 398 x 10(6)/l and 310 x 10(6)/l in Groups I and II respectively. In the intent-to-treat (ITT; missing value = failure) analysis at 48 weeks, HIV-1 RNA was < 400 copies/ml for 91% (< 50 copies/ml, 75%) and 82% (< 50 copies/ml, 79%) of patients in groups I and II respectively. Mean steady-state ABT-378 trough concentrations exceeded the wild-type HIV-1 EC50 (effective concentration to inhibit 50%) by 50-100-fold. The most common adverse events were abnormal stools, diarrhea and nausea. No patient discontinued before 48 weeks because of treatment-related toxicity or virologic rebound. CONCLUSIONS: ABT-378 is a potent, well-tolerated protease inhibitor. The activity and durable suppression of HIV-1 observed in this study is probably attributable to the observed tolerability profile and the achievement of high ABT-378 plasma concentrations. PMID- 11192875 TI - Early clinical results: SOUNDTEC implantable hearing device phase II study. AB - OBJECTIVE: To assess the safety and efficacy of a new semi-implantable electromagnetic hearing device, the SOUNDTEC Direct Drive Hearing System (DDHS), and to compare its performance with that of subjects' previously worn, optimally fit hearing aids. Preliminary results for the first 10 subjects are presented. STUDY DESIGN: The protocol specified in the Investigational Device Exemption is used in this ongoing FDA phase II 100-subject multicenter clinical trial. METHODS: For baseline, each subject is tested wearing his or her own optimally fit hearing aid in the ear to be implanted. Six-month postoperative outcome measures using the SOUNDTEC DDHS are compared with the baseline. Multiple objective and subjective outcomes (as listed under Results) were measured. RESULTS: When compared with the subjects' optimally fit hearing aids, the SOUNDTEC DDHS provided an average improvement of 52% in functional gain (250-6000 Hz), 22% in aided thresholds, 3.8% for speech discrimination in quiet, 17% for speech in noise, 13.1% in articulation index scores, 28% in aided benefit, 27.3% in sound quality of speech, and a 16.7% increase in overall subject satisfaction. In addition, with the SOUNDTEC DDHS, subjects reported absence of acoustic feedback, little or no occlusive effects, and more natural sound perception. CONCLUSION: Analysis of data on the first 10 subjects using the SOUNDTEC DDHS indicates positive outcomes regarding safety and efficacy, although the small sample size is not sufficient to permit valid statistical inferences to be drawn from our preliminary data. Results also demonstrate improvement in performance compared with the subjects' optimally fit hearing aids and an improvement in quality of life as demonstrated by objective and subjective tests and measures. PMID- 11192876 TI - Distortion-product otoacoustic emissions and glycerol testing in endolymphatic hydrops. AB - OBJECTIVES/HYPOTHESIS: Aural fullness is a frequent symptom of endolymphatic hydrops. Its evaluation may provide valuable information on the initial stage of development of endolymphatic hydrops. STUDY DESIGN: The present investigation was specifically designed to ascertain the ability of the glycerol test, combined with pure tone audiometry and distortion product otoacoustic emissions (DPOAEs) testing, to diagnose endolymphatic hydrops early and to identify patients who may evolve toward Meniere's disease. For these purposes, patients who complained about aural fullness as their only audiologic symptom were selected. METHODS: This investigation consisted of 19 consecutive patients with unilateral or bilateral aural fullness who received no treatment. Each patient underwent glycerol testing measured with conventional pure tone audiometry and with both DPOAEs. For the traditional pure-tone glycerol test, a hearing improvement of at least 10 dB, at the lower two or three frequencies (125, 250, and 500 Hz), was judged as a positive result. For the DPOAE glycerol test, a smaller positive difference (5 dB) for at least three frequencies was interpreted as an ameliorative fluctuation. RESULTS: The outcomes of the glycerol tests (24 ears examined) showed variable patterns. Seven ears showed no significant changes of either the pure-tone audiogram or DPOAE. In seven other ears, the comparison of the traditional glycerol test and the DPOAE glycerol test indicated an improvement in both measures. Another seven ears showed negative glycerol tests, whereas DPOAE responses gradually recovered reaching levels significantly higher than those recorded before glycerol administration. The three remaining ears showed contrasting results. CONCLUSIONS: Patients with aural fullness in the absence of other associated symptoms may potentially be in the initial stages of Meniere's disease. This notion is confirmed by the present findings showing a high rate (58%) of positive glycerol tests in the selected patients. The importance of DPOAE testing is supported by their ability to detect minimal dysfunction, possibly representing endolymphatic hydrops that goes undetected by routine pure-tone audiometry. PMID- 11192877 TI - Vestibular end-organ impairment in an animal model of type 2 diabetes mellitus. AB - OBJECTIVES/HYPOTHESIS: To define and assess the functional impairment of the vestibular part of the inner ear in a diabetic state, using a direct and objective test for evaluating the vestibular end-organ and an animal model for diet-induced type 2 diabetes mellitus. STUDY DESIGN: Prospective controlled animal study. METHODS: Two groups of sand rats (Psammomys obesus) were maintained on two different diets. The experimental group received a specially designed high energy diet known to induce a diabetic state, and the control group a low-energy diet maintaining these animals in a normal metabolic state. After 1 month of documented hyperglycemia in the experimental group, recordings of vestibular evoked potentials (VsEPs) and recordings of auditory brainstem response (ABR) were conducted in all animals. The latency and the amplitude of the first wave of both responses, shown to reflect end-organ activity, were compared between the two groups. RESULTS: The mean latency of the first wave of the VsEPs was significantly (P = .002) prolonged and the amplitude was significantly (P = .005) decreased in the diabetic group in comparison to the control group. The latency of the first wave of ABR was significantly (P = .02) prolonged, the amplitude was not significantly decreased, and threshold was significantly elevated (P = .01) in the diabetic group. CONCLUSION: For the first time, using an objective assessment test, functional impairment of the vestibular part of the inner ear has been demonstrated in the diabetic metabolic state. Despite this being an animal study, these findings would seem to indicate that the vestibular-end-organ should be added to the long list of organs and tissues adversely affected by diabetes. PMID- 11192878 TI - Chronic otitis media sequelae in skeletal material from medieval Denmark. AB - OBJECTIVES: Chronic otitis media sequelae (COMS) have been identified in archaeological skeletal materials from various ages. COMS reflecting episodes of upper respiratory tract infection may be used as a paleopathological indicator of general health. Estimation of the frequency of COMS may be useful in the gross evaluation of general standard of living. MATERIALS AND METHODS: Temporal bones and auditory ossicles from 659 individuals from two Danish medieval rural parish cemeteries, dated to 1050-1200 and 1150-1350, respectively, were examined otomicroscopically. RESULTS: Osseous fistulae from mastoid abscesses, remodelling of the hypotympanon, and erosion of the incus were among the convincing indications of COMS. A minimum frequency of COMS of 1% to 7% was found. The youngest material displayed the highest frequency of pathological changes. CONCLUSION: Indications of a rising incidence of infectious middle ear disease in early medieval Denmark were found. This may reflect a deterioration of living conditions from the 11th through the 14th centuries. PMID- 11192879 TI - Complications associated with the Sistrunk procedure. AB - OBJECTIVE: To assess the type and rate of complications in the postoperative period of pediatric patients undergoing the Sistrunk procedure. STUDY DESIGN: A retrospective review of patients with a diagnosis of thyroglossal duct cyst who had not had corrective surgery previously. An attempt to standardize the study was made as follows: all patients had surgery under the direction of one surgeon, using the Sistrunk procedure with minor modifications from its original description. Complications were divided into major and minor categories. METHODS: Charts were reviewed for age, sex, preoperative assessment, and postoperative follow-up. Complications were recorded. A postoperative telephone survey was conducted. RESULTS: A minor complication rate of 29% was observed. There were no recurrences or major complications. CONCLUSIONS: The Sistrunk procedure remains the operation of choice for removal of the thyroglossal duct cyst. When the surgery is properly performed, with attention to key surgical landmarks, the risk of major complication is minimal. Complications that do occur are minor and wound related. PMID- 11192880 TI - Overexpression of p53-related proteins predicts rapid growth rate of head and neck cancer. AB - OBJECTIVES/HYPOTHESIS: The p53 tumor suppressor gene plays an important role for cell cycle regulation and is the most frequent mutated gene in head and neck cancer. Controversy remains regarding the biological and clinical value of immunohistochemical identification of the proteins accumulated in association with inactivation of the p53 gene and increased tumor growth. Therefore, the objective of the present study was to perform a cell kinetic analysis of cases with untreated squamous cell carcinoma and to compare the result with immunostaining for p53-related proteins in the tumor cells. STUDY DESIGN: A prospective series of 32 patients presenting with various stages of untreated squamous cell carcinoma of the head and neck were included. Bromodeoxyuridine (BrdU) was injected as a tracer dose before tumor biopsy for cell kinetic analysis, and p53 protein accumulation was detected using two antibodies (DO7 and PAb 1801). RESULTS: Antibody DO7 showed the highest and the optimal immunoreactivity. Diploid tumors were found in 27 cases (84%), and the mean potential doubling time (Tpot) was 55 +/- 7 hours for these tumors. Positivity of DO7 (>1%) was demonstrated in 85% of the cases. However, a discrimination level exceeding 20% was required to obtain a significant negative relationship (Spearman's rank correlation coefficient test, P < or = .03) between Tpot and DO7 positivity. At that level, 33% of the tumors remained DO7-positive. The corresponding Tpot was not significantly different from the overall mean. The rates of metastatic disease and survival were not dependent on DO7 immunoreactivity or cancer cell kinetics. CONCLUSION: Accumulation of p53-related proteins is associated with an unrestrained growth of head and neck cancer. PMID- 11192881 TI - A prospective study of p53 expression and its correlation with clinical response of radiotherapy in nasopharyngeal carcinoma. AB - OBJECTIVES/HYPOTHESIS: Nasopharyngeal carcinoma (NPC) is a common malignant neoplasm of the head and neck that occurs in people in the southeastern Asian area, including Taiwan. The significant association of p53 expression in NPC suggested that p53 overexpression seemed to occur at an early stage in the development of NPC. Alterations of p53 status were probably the most commonly encountered in head and neck carcinomas, and there was extensive evidence that p53 status might determine tumor response to therapy. Ionizing radiation was studied extensively for the relationship between its damaging effect and p53 status in human cancer cells. STUDY DESIGN: This study was carried out to investigate whether there was any correlation between overexpression of p53 protein and locoregional tumor response in patients with NPC treated with 7000 cGy of radiotherapy. METHODS: Sixty-eight patients (50 males, 18 females) with NPC who were diagnosed and treated with radiotherapy were studied prospectively. Before they had received a radiation dose of 7000 cGy in 35 fractions, five fractions a week, p53 status from a nasopharyngeal biopsy was studied using immunohistochemical staining (IHC). RESULTS: The locoregional response rate of primary tumor was analyzed statistically. Forty-seven patients (69.1%) showed positive p53 staining in their tumors. There were 5 positive stains in 6 squamous cell carcinomas (SCC; 83.3%), 34 positive in 53 non-keratinizing carcinomas (NKC; 64.2%), and 8 positive in 9 undifferentiated carcinomas (UC; 88.9%). The mean ages for patients with three different histopathologies were 48.5, 46.1, and 61.1 years. There were 8 patients (7 positive stains, 1 negative stain) with residual tumor after radiotherapy and all were NKC (6 males, 2 females). Therefore, the clinical response rate of primary tumor was 85.1% in positive p53 immunostaining (40 of 47 cases), 95.2% in those with no immunostaining (20 of 21 cases); the former was poorer in locoregional tumor response than the latter, but there was no significant difference (P > .05, chi2 test). CONCLUSIONS: We conclude that there is no statistically significant correlation in locoregional response of primary tumor between p53 overexpression and radiotherapy in patients with NPC (P > .05, Fisher exact test). PMID- 11192882 TI - Modern concepts of frontal sinus surgery. AB - OBJECTIVES/HYPOTHESIS: To validate the endonasal surgical approach to frontal sinus in inflammatory sinus disease, trauma, and selective tumor surgery, and to define the role of external approaches to the frontal sinus. Endonasal frontal sinusotomy can range from endoscopic removal of obstructing frontal recess cells or uncinate process to the more complex unilateral or bilateral removal of the frontal sinus floor as described in the Draf II-III drainage procedures. In contrast, the osteoplastic frontal sinusotomy remains the "gold standard" for external approaches to frontal sinus disease. METHODS: A retrospective review of 1286 patients undergoing either endonasal or external frontal sinusotomy by the authors at four university teaching programs from 1977. Prior author reports were updated and previously unreported patient series were combined. RESULTS: Six hundred thirty-five patients underwent type I frontal sinusotomy, 312 type II sinusotomy, and 156 type III sinusotomy. A successful result was seen in these groups, 85.2% to 99.3%, 79% to 93.3%, and 91.5% to 95%, respectively. External frontal sinusotomy or osteoplastic frontal sinusotomy was successfully performed in 187 of 194 patients. Clinical symptoms, endoscopic findings, computed tomography, and magnetic resonance image scanning, and reoperation rate measured postoperative success. CONCLUSIONS: A stepwise approach to the surgical treatment of frontal sinusitis, trauma, and selective benign tumors yields successful results as defined by specific criteria which vary from 79% to 97.8%. The details of specific techniques are discussed, essential points emphasized, and author variations noted. PMID- 11192883 TI - Argon plasma surgery for the inferior turbinate of patients with perennial nasal allergy. AB - OBJECTIVES: Argon plasma coagulation (APC) is a new electrosurgical modality. The advantages of APC are coagulating of the target tissue without contact and the creation of uniformly deep devitalized and coagulated zones. The objectives of the present study were to determine the clinical effects of APC for the inferior turbinate of patients with nasal allergy and to clarify the histological changes in the mucosa after APC. STUDY DESIGN: In a prospective study, 95 patients with perennial nasal allergy were treated with APC. Nasal symptoms and intranasal findings were evaluated preoperatively and 1, 3, and 6 months, and 1 year after the APC. Mucosal specimens from the turbinates were examined under light and electron microscopy. RESULTS: Nasal stuffiness was improved in 77 of 79 (97.5%) patients after 1 month, in 50 of 51 (98.0%) patients after 3 months, in 20 of 23 (87.0%) patients after 6 months, and in 9 of 12 (75.0%) patients at 1 year after the APC. Rhinorrhea was improved in 46 of 75 (61.3%) patients after 1 month, in 40 of 51 (78.4%) patients after 3 months, in 16 of 21 (76.2%) patients after 6 months, and in 6 of 10 (60.0%) patients at 1 year after the APC. The sneezing was improved in 32 of 54 (59.3%) patients after 1 month, in 21 of 35 (60.0%) patients after 3 months, in 10 of 14 (71.4%) patients after 6 months, and in 6 of 8 (75.0%) patients at 1 year after the APC. In the intranasal findings, congestion of the inferior turbinate improved in 75 of 76 (98.7%) patients after 1 month, in 49 of 52 (94.2%) patients after 3 months, in 20 of 23 (87.0%) patients after 6 months, and in 7 of 11 (63.6%) patients at 1 year after the APC. The nasal discharge was reduced in 40 of 75 (53.3%) patients after 1 month, in 32 of 52 (61.5%) patients after 3 months, in 15 of 22 (68.2%) patients after 6 months, and in 5 of 11 (45.5%) patients at 1 year after the APC. No patients needed nasal packing after the APC. CONCLUSIONS: This is the first report on the clinical effects of turbinate surgery for nasal allergy using APC. APC was useful fer turbinate surgery of nasal allergy, especially for nasal stuffiness and congestion of the turbinate. PMID- 11192884 TI - Insecticidal activity of common reagents for insect foreign bodies of the ear. AB - OBJECTIVE: Insects commonly present as painful and distressing foreign bodies of the external ear canal. Removing live insects can be challenging, especially for primary care physicians who have limited equipment. The purpose of this study is to compare the insecticidal activity of commonly available preparations for insects that are most frequently recovered from ear canals: cockroaches (German and American), ticks, beetles, and honeybees. STUDY DESIGN: Prospective, blinded. METHODS: One hundred seventy insects of each species were placed in test tubes and submerged in 17 test preparations (10 tubes per preparation, 1 insect per test tube). Insect activity was stimulated by agitation of the test tube. Responses were monitored, and the time until death was measured. RESULTS: Most test preparations exhibited some insecticidal activity against most insect species. Ticks were completely resistant to all of the test reagents. Ethanol killed the American cockroaches (mean time, 32.6 s), German cockroaches (mean time, 29.6 s), and honeybees (mean time, 19.6 s) the most rapidly. CONCLUSION: Many commonly available reagents may be used to kill or immobilize insect foreign bodies of the ear. PMID- 11192885 TI - Changes of nasal function after temperature-controlled radiofrequency tissue volume reduction for the turbinate. AB - OBJECTIVES: Temperature-controlled and temperature-monitored radiofrequency tissue volume reduction (RFTVR) for the turbinate is a new treatment modality for nasal obstruction secondary to turbinate hypertrophy. We compared the nasal functions after the treatment ofRFTVR and laser vaporizing turbinoplasty (LVT) using subjective symptom scores and objective tests. STUDY DESIGN: Prospective, randomized clinical trial. METHODS: Twenty-four patients with nasal obstruction secondary to inferior turbinate hypertrophy were prospectively evaluated from March 1999 to October 1999 at Seoul National University Hospital (Seoul, Korea). Sixteen patients were treated with RFTVR, and eight patients with LVT. The preoperative and postoperative nasal functions were investigated by visual analogue scale of symptoms, butanol threshold test, saccharine test, acoustic rhinometry, rhinomanometry, and ciliary beat frequency. RESULTS: At 8 weeks postoperatively, the severity and the frequency of nasal obstruction improved subjectively in 81.3% and 93.8% of RFTVR group and in 87.5% and 87.5% of LVT group, respectively. Significant improvement of nasal symptoms began from 2 to 3 days after the operation in the RFTVR group, whereas there was significant improvement of nasal symptoms at 8 weeks after operation in the LVT group. However, objective nasal functions including nasal volume and total nasal resistance were significantly improved at 8 weeks after surgery in both groups. Among patients reporting symptoms of hyposmia, 55.6% of RFTVR group and 63.6% of LVT group showed improved olfaction. Saccharin transit time and ciliary beat frequency were preserved after RFTVR CONCLUSION: RFTVR for the turbinate may be useful as an alternative approach for the treatment of chronic turbinate hypertrophy. PMID- 11192886 TI - Local vasodilator response to mobile phones. AB - OBJECTIVES: The use of mobile phones with the resulting generation of potentially harmful electromagnetic fields (EMF) is the focus of public interest. Heat generation and the activation of the inducible form of nitric oxide (NO) synthase may be possible causes of the biological effects of EMF exposure. We investigated if a mobile telephone conversation can modify skin temperature, NO, and nasal resistance. METHODS: We studied the effect of an EMF (900 MHz) generated by a commercially available cellular phone during a 30-minute telephone conversation on skin temperature, nasal NO measured by chemiluminescence, and nasal minimal cross-sectional area (MCA) measured by rhinometry. Eleven normal subjects (mean age +/- standard error of mean [SEM], 32 +/- 5 y; 10 male) were studied. RESULTS: There was a similar and significant increase in skin temperature of the nostril and occipital area on the same side as the telephone (maximal increase 2.3 +/- 0.2 degrees C at 6 min) as well as a tendency for higher nasal NO levels (maximal increase 12.9 +/- 4.9% at 10 min), whereas the MCA was significantly reduced (maximal decrease -27 +/- 6% at 15 min). Such changes were not recorded when an earpiece was used to avoid the direct exposure to the electromagnetic field. There were no changes in the skin temperature and nasal NO measured on the opposite side to the mobile phone, whereas the MCA was significantly increased (38 +/- 10%). CONCLUSIONS: Exposure to EMF produced by a mobile phone produces biological effects that can be easily measured. Microwaves may increase skin temperature and therefore cause vasodilation and reduce MCA. Further studies are needed to study the long-term effects of mobile phone use and the relation among NO production, vasodilation, and temperature. PMID- 11192887 TI - Evaluation of the effect of passive smoking on otitis media in children by an objective method: urinary cotinine analysis. AB - OBJECTIVES: We aimed to determine objectively the effect of the passive smoking on otitis media with effusion (OME) and recurrent otitis media (ROM) by using the method of cotinine urinalysis. STUDY DESIGN: We designed a prospective case control study with follow-up of the case group for 1 year after insertion of tympanostomy tubes to evaluate postoperative complications such as otorrhea and early extrusion (<6 months), in case a significant risk factor was found. METHODS: One hundred fourteen children between 3 and 8 years of age requiring tympanostomy tubes because of OME and ROM were chosen and compared with 40 age matched children. Exposure to environmental tobacco smoke was assessed by cotinine urinalysis, which was performed by means of the radioimmunoassay method. RESULTS: In this study, 73.7% (84 of 114) of the children in the case group and 55.0% (22 of 40) of the children in the control group were found to be "exposed" (P = .0461). This difference was statistically significant. Comparing the cotinine urinalysis results with parental smoking histories, 23.1% (9 of 39) of the children without parental smoking histories were "exposed" to tobacco smoke versus 84.3% (97 of 115) of the children with parental smoking histories (at least one person smoking). CONCLUSIONS: Our results indicate that sidestream smoking increases the risk of OME and ROM. Legal regulations and guidelines must be established to protect children from passive smoking. Because cotinine urinalysis is a noninvasive and reliable method for the determination of passive smoking, it can be used for that purpose. PMID- 11192888 TI - Laser arytenoidectomy for bilateral median vocal fold fixation. PMID- 11192889 TI - A new turbinoplasty technique for the management of concha bullosa: our short term outcomes. PMID- 11192890 TI - Target-controlled infusion in sleep endoscopy. PMID- 11192891 TI - Primary intubation of cartilage tympanoplasties. PMID- 11192892 TI - Office myringoplasty with alloderm. PMID- 11192893 TI - Is it time to develop an 'ultrastaging system' for use in patients with head and neck malignancies? PMID- 11192894 TI - Pediatric fluctuating sensorineural hearing loss: problems in medical management. AB - OBJECTIVES: To discuss the diagnosis and management of children with fluctuating sensorineural hearing loss, especially focusing on those problems dealing with autoimmune inner ear disease. STUDY DESIGN: A retrospective chart review of a large pediatric otolaryngology practice. A series of 40 children with progressive hearing losses was identified. Of that group, 22 children, aged 1.5 to 12.2 years at first audiogram, were considered to have fluctuating sensorineural hearing loss (FSNHL). Criteria for inclusion in the FSNHL group were threshold variations of 15 dB or more in at least one ear at two or more of the standard audiometric frequencies on at least 2 testing days. METHODS: Charts were reviewed for age, sex, otologic history, laboratory evaluations, medical or surgical treatments, significant medical history, and family medical history. RESULTS: Twenty-two children met the criteria for fluctuating sensorineural hearing loss. Of those with fluctuating hearing loss, 15 were idiopathic, 3 had positive lymphocyte transformation tests (LTT) suggestive of autoimmune inner ear disease (AIED), and 4 had fistula on middle ear exploration. Average fluctuation for all groups was 29.1 dB. Average duration of fluctuations was 4.95 years. CONCLUSIONS: The majority of pediatric FSNHL cases (15 of 22) were idiopathic in nature. Of those FSNHL children with positive LTTs, only one was treated with steroid therapy. In the other patients with positive LTTs, parents or other physicians were often reluctant to treat, or the patient was lost to follow-up. Mean fluctuations varied substantially across all standard audiometric frequencies for all groups. PMID- 11192895 TI - Outcome analysis of cochlear implant reimplantation in children. AB - OBJECTIVES: We review our experience gained in performing cochlear reimplantation in 25 children who have had multichannel cochlear implant device failure at the Cochlear Implant Center of the Manhattan Eye, Ear and Throat Hospital and Lenox Hill Hospital (New York, NY), to assess the feasibility of cochlear reimplantation in children and the effect of reinsertion on audiological performance. STUDY DESIGN: We retrospectively analyzed the outcome of 27 consecutive multichannel cochlear implant reinsertions performed in 25 children at the Manhattan Eye, Ear and Throat Hospital and Lenox Hill Hospital. These reimplantations were performed between 1990 and 1999, with a minimum follow-up of 6 months for both surgical and audiological performance. METHODS: Charts were reviewed for patient factors, findings at the time of initial operation and repeat operation, and results of audiological testing both before and after reimplantation. RESULTS: Surgical complications of reimplantation included two intraoperative cerebral spinal fluid leaks and two late postoperative flap breakdowns with implant extrusions. For the most part, depth of electrode insertion was unchanged. Open-set speech recognition scores and speech perception abilities remained stable or improved compared with results before reimplantation. CONCLUSION: Our results confirm that cochlear implant reimplantation is technically feasible and allows for continued auditory development for the child who has a cochlear implant device failure. PMID- 11192896 TI - Management of acute pulmonary hemorrhage in children. AB - OBJECTIVE: Acute pulmonary hemorrhage can result from a variety of causes. This report offers a diagnosis and treatment plan for children with acute, life threatening pulmonary hemorrhage resulting from a variety of causes. METHODS: Retrospective review of children with acute pulmonary hemorrhage cared for at a tertiary care children's hospital during from January 1, 1993 to September 1, 1999. PATIENTS: Fourteen children were identified with life-threatening pulmonary hemorrhage during the study period. INTERVENTIONS: Bronchoscopy was the keystone to diagnosis of pulmonary hemorrhage in this series. All of the children underwent multiple procedures to stabilize the airway and control blood loss. These interventions included CO2 laser bronchoscopy, Nd-YAG laser bronchoscopy, endoscopic balloon occlusion of a lobe or main bronchus, topical airway vasoconstrictors, endoscopic tumor excision, transcatheter embolization of bronchial vessels, and lobectomy. OUTCOMES: Three children died and 11 survived without neurological sequelae. CONCLUSIONS: Control of acute pulmonary hemorrhage is a difficult problem and often requires multiple procedures. Endoscopic control is usually required for palliation until more definitive therapy can be undertaken. PMID- 11192897 TI - A histologic analysis of three-dimensional versus two-dimensional tissue expansion in the porcine model. AB - OBJECTIVE: Recently, a two-dimensional Silastic Dacron stretching skin device has been developed for scalp reduction surgery. Attached subgaleally, this device stretches skin over time, while avoiding the visible volumetric distention that is typical of three-dimensional tissue expanders. Unlike three-dimensional expanders, the histological changes observed with a two-dimensional stretching device have not been described in the literature. The present study compares the histological effects of two-dimensional and three-dimensional skin tissue expansion in the porcine model. STUDY DESIGN: A university Institutional Review Board-approved study in which 16 domestic piglets were used. The 16 piglets were divided evenly into four cohorts as follows: 1, 1-week control cohort; 2, 1-week experimental cohort; 3, 4-week control cohort; and 4, 4-week experimental cohort. METHODS: Tissue expanders (three-dimensional) and Dacron Silastic tissue stretchers (two-dimensional) were surgically inserted into the lateral skin of 16 domestic pigs. Animals were killed at either 1 or 4 weeks based on group assignment. Light microscopic ocular micrometry and stereological point counting were used to determine the depth of the epidermis, dermis, and subdermal adipose tissue layer; width of the panniculus muscle; diameter of sweat gland follicles; percentage ratio of dermal collagen, blood vessels, and tissue space; and epidermal mitotic index in 100 specimens. One-way ANOVA was used to evaluate statistical differences. RESULTS: Both tissue expanders yielded increased values compared with control subjects, with respect to epidermal, dermal, and fat widths and blood vessel counts, whereas adnexal structures in the panniculus muscle width were unaltered. CONCLUSIONS: Although statistically the two types of expansion produced histologically similar changes, the degree of change varied according to the type of expander that was used and the duration of tissue expansion. Most notably, three-dimensional expansion produced more tissue gain per unit area expanded at both the 1-week and the 4-week time intervals, and early (1-week) two-dimensional tissue expansion stimulated a greater angiogenic response than three-dimensional expansion. These findings will assist the surgeon in understanding the physical changes that occur with these two forms of tissue expansion, as well as the potential clinical advantages and shortcomings of each method. PMID- 11192898 TI - Endoscopic arytenoid repositioning for unilateral arytenoid fixation. AB - OBJECTIVES: To describe a new endoscopic technique for medialization of the laterally fixed arytenoid. The surgical technique, endoscopic arytenoid repositioning, is described, and the results of a series of cases are discussed. STUDY DESIGN: Retrospective chart review. METHODS: Eight patients underwent the procedure. Six patients were available for long-term follow-up. Preoperative and postoperative voice ratings were compared to evaluate the success of the procedure. Follow-up ranged from 3 to 64 months (mean follow-up, 31.5 mo). RESULTS: Long-term follow-up in six cases revealed that 67% (4 of 6) patients had normal or near-normal postoperative voices and one patient experienced moderate improvement. The mean preoperative voice score was 4.24, and the mean postoperative voice score was 1.83 (range, 1-5). The difference was statistically significant (P < 0.001). CONCLUSIONS: Endoscopic arytenoid repositioning is a newly described procedure with a very specific indication: a unilateral, laterally fixed arytenoid complex resulting in a severely dysphonic voice. Though technically demanding, this procedure provides a promising option for medialization of the posterior glottis in a scarred larynx. PMID- 11192899 TI - Neonatal subglottic stenosis--incidence and trends. AB - OBJECTIVE/HYPOTHESIS: Neonatal subglottic stenosis is a known entity arising from endotracheal tube intubation. In the 1970s and 1980s, estimates of the incidence of subglottic stenosis were in the range of 0.9% to 8.3% of intubated neonates. Because of improved techniques of handling neonates who require ventilatory support, we thought the actual incidence of neonatal subglottic stenosis in the late 1990s was much lower. STUDY DESIGN: We retrospectively reviewed all neonatal intensive-care unit (NICU) admissions from 1997 at our institution, which serves as a level 3 NICU. We also performed a MEDLINE search of the reported incidence of neonatal subglottic stenosis between 1960 and 1999. METHODS: Analysis was performed to identify all children who developed subglottic stenosis at our institution. Data were also collected and analyzed with regard to average gestational age, average birth weight, average duration of intubation, and the number of children requiring tracheostomy. The reports identified in the literature were reviewed as to the incidence of subglottic stenosis. RESULTS: A total of 544 neonates were admitted to the unit. Of these, 281 were intubated for an average of 11 days. No patients developed subglottic stenosis. Three patients required tracheostomies for other reasons. All studies published after 1983 reported an incidence of neonatal subglottic stenosis as less than 4.0%, and all studies published after 1990 reported an incidence of neonatal subglottic stenosis as less than 0.63%. CONCLUSIONS: Although our report applies to only a single institution in a single year, after reviewing the literature we think a downward trend exists in the incidence of neonatal subglottic stenosis in the late 1990s. The current incidence of neonatal subglottic stenosis is likely between 0.0% and 2.0%. PMID- 11192900 TI - Electroporation therapy for head and neck cancer including carotid artery involvement. AB - OBJECTIVES: Electroporation therapy with intralesional bleomycin (EPT) is a novel, technically simple outpatient technique in which high-voltage electric impulses delivered into a neoplasm transiently increase cell membrane permeability to large molecules, including cytotoxic agents, causing localized progressive necrosis. Unlike many laser ablation methods, EPT can treat bulky tumors (>2 cm) with complete penetration. Our recent publication confirms an excellent response rate in the use of EPT in a clinical trial. STUDY DESIGN, PATIENTS, AND METHODS: Following our initial prospective study report in 1998, we have followed our entire initial cohort (10 patients) of patients with head and neck cancer beyond 24-months follow-up. Additionally, we have used this approach to treat four additional patients (total: 9 males/5 females) with upper aerodigestive tract squamous cell carcinoma, including three with internal carotid artery (ICA) involvement up to or within the skull base. Two patients underwent preoperative balloon test occlusion with cerebral perfusion studies followed by carotid embolization. EPT was then done safely at least 2 weeks later to avoid the temporary hypercoagulable state. RESULTS: Within the overall cohort (14 patients) 6 patients had a complete response, 6 had a partial response, and 2 did not respond (overall 85.7% response rate). Both patients with ICA involvement had a partial or complete response to treatment; neither patient had a hemorrhagic or neurologic complication. Overall, 13 of the 14 patients were treated for persistent or recurrent head and neck cancer. Two of the four patients with early recurrent stage tumors had no evidence of recurrence after EPT with an average follow-up of 31.5 months. The overall early stage tumor group had four complete responders out of five (80%). On the contrary, only 2 of 9 patients with advanced recurrent stage tumors were disease-free at 18 months. Morbidity was low for early stage tumors, but higher for advanced tumors with complications, including poor wound healing, dysphagia, and osteomyelitis. There were no treatment-related deaths. CONCLUSION: We found EPT to be safe and efficacious in patients with head and neck cancer, even with internal carotid artery involvement. Patients with early stage recurrences have the potential for prolonged survival beyond 2 years without the morbidity of surgery and radiation or toxicity of systemic chemotherapy. Because of its superb access qualities even for bulky tumors, EPT is a potential method of delivery for other tumoricidal agents such as in genetic-altering schemes. PMID- 11192901 TI - Recurrent respiratory papillomatosis. AB - Recurrent respiratory papillomatosis (RRP) is the most common benign neoplasm of the larynx in children. Despite its benign histology, RRP has potentially morbid consequences and is often difficult to treat because of its tendency to recur and spread throughout the respiratory tract. Long neglected from an epidemiological standpoint, recent initiatives to better understand this disease process have been launched through coordination between the Centers for Disease Control and Prevention and the American Society of Pediatric Otolaryngology. In this clinical review, I discuss what we currently know regarding the etiology, epidemiology, and transmission of this disease. Clinical features including pertinent aspects of the history, physical examination, airway endoscopy, and other considerations are highlighted. A detailed description of the surgical and anesthetic management of these challenging cases is presented. Adjuvant modalities of surgical and nonsurgical treatment and their indications are discussed. Ongoing research initiatives and the Practice Guidelines of the Recurrent Respiratory Papillomatosis Task Force are also included. PMID- 11192902 TI - Building the powerful 10-minute office visit: Part II. Beginning a critical literature review. AB - OBJECTIVE: This is the second part in a series of sequential Tutorials in Clinical Research. The objective of this tutorial is to introduce methods of searching the vast stores of information now available, to review some of the computer resources available, to reintroduce the concept of an a priori design for the search, and to reveal the need for assessment of the clinical importance and validity of each pertinent article found. STUDY DESIGN: Tutorial. METHODS: An open working group has been formed with the specific aim of surveying and translating the large volume of complex information on research design and statistics into easily understood, useable, and non-threatening tutorials for the busy practitioner. The hypotheses under which this work is conducted are highly intelligent, but extremely busy, surgeons are interested in evidence-based medicine and will increase personal participation in critical reading of the literature, pending an expanded familiarity with clinical research design and statistics. RESULTS: Available resources for literature searching, methods of quick personal overviews, and quick question-specific reviews are discussed. Additionally, the methods, with examples, of beginning a critical literature review are presented. CONCLUSIONS: Rapid, personal, critical literature review requires succinct formulation of the question, efficient search for the best available evidence, and critical appraisal of the pertinent individual articles to determine if sufficient evidence exists to support a clinical contention. PMID- 11192903 TI - Preoperative functional assessment of auditory cortex in adult cochlear implant users. AB - OBJECTIVES: To explore functional neuroanatomical responses to auditory stimulation before and after implantation. STUDY DESIGN: A prospective study of three cochlear implant candidates (pure-tone averages of 90 dB HL or greater bilaterally and hearing in noise test [HINT] performances of <40%) in which regional cerebral blood flow (rCBF) was assessed using single photon emission computed tomography (SPECT). METHODS: Candidates watched a 15-minute videotaped story under four conditions: audio presented monaurally in the right and left ears (aided), audio presented binaurally (aided), and visual-only presentation of the story. Five minutes into each story, 20 to 25 mCi of technetium 99m (99mTc) hexamethyl-propyleneamine-oxime (HMPAO) (Ceratec; Nycomed Amersham, Princeton, NJ, U.SA) was injected over a 30-second period to ensure that subjects were unaware of tracer administration. Subjects were scanned for 20 minutes using a PRISM 3000 gamma camera (Picker International, Cleveland, OH, U.S.A.). Data were normalized and co-registered, and subtraction images were compiled. Subtraction images contrasted activation patterns generated under the visual-only control condition to the auditory activation states acquired monaurally and binaurally. RESULTS: Right and left ear monaural stimulation in normal hearing subjects resulted in significant bilateral activation of Brodmann areas 41, 42, 21, 22, and 38. Although substantial intersubject response variability was noted, subjects generally failed to bilaterally activate these areas under monaural hearing aid presentations; however, bilateral activation of areas 41 and 22 was noted under binaural presentations. CONCLUSIONS: Despite relatively similar hearing losses in each ear, significant differences in preoperative auditory cortex activation were observed between ears. These data suggest that functional brain imaging provides a useful tool for exploring the responsiveness of the auditory cortex in cochlear implant candidates. PMID- 11192904 TI - A new clinical classification for Usher's syndrome based on a new subtype of Usher's syndrome type I. AB - OBJECTIVES: Usher's syndrome is an autosomal recessive disorder characterized by sensorineural hearing loss and progressive visual loss secondary to retinitis pigmentosa. Usher's syndrome is both clinically and genetically heterogeneous. Three clinical types are known today. METHODS: We conducted a study on 74 patients with Usher's syndrome, performing complete audiological and neurotological examinations. RESULTS: Twenty-six patients had total profound hearing loss and retinitis pigmentosa (Usher's syndrome type I), and 48 patients had moderate to severe sensorineural hearing loss and retinitis pigmentosa (Usher's syndrome type II). We identified 9 of the 26 Usher's syndrome patients with profound hearing loss who showed a normal response to bithermal vestibular testing. CONCLUSIONS: The combination of profound hearing loss and normal response to bithermal vestibular testing has not been previously described in Usher's syndrome. Therefore we describe a new subtype of Usher's syndrome type I and suggest a modified clinical classification for Usher's syndrome. PMID- 11192905 TI - Atypical indications for OtoScan laser-assisted myringotomy. AB - OBJECTIVE: To describe the role of OtoScan laser-assisted myringotomy (OtoLAM) for indications other than chronic otitis media or recurrent acute otitis media. STUDY DESIGN: Cross-sectional review. METHODS: Twenty-seven office-based OtoLAM procedures were performed in 21 patients for "atypical" reasons. The indications included middle ear dysfunction with necessary air travel (n = 10) or hyperbaric oxygen treatment (n = 6), mastoiditis with postauricular cellulitis (n = 2), canal exostosis prohibiting tympanostomy (n = 1), acute otitis media accompanied by seizures (n = 1), and chronic middle ear effusion in a patient with hemophilia (n = 1). RESULTS: In each of the 20 cases available for follow-up, middle ear disease resolved with closure of the laser-assisted myringotomy. At a later date, two patients (10%) underwent another OtoLAM in the opposite ear and four patients (20%) required repeat OtoLAM in the same or both ears. Three patients (15%) ultimately underwent myringotomy tube placement because of recurrent middle ear dysfunction. CONCLUSIONS: Although this report contains preliminary data, the data suggest that OtoLAM may provide an additional option in the care of certain patients who have previously been treated with myringotomy tubes. PMID- 11192906 TI - The diagnosis of a conductive olfactory loss. AB - OBJECTIVES/HYPOTHESIS: Two of the most common causes of olfactory loss include upper respiratory infection (URI) and nasal or sinus disease. The etiology of most URI-related losses is thought to be viral and, as yet, there is no available treatment. In contrast, nasal or sinus disease produces an obstructive or conductive loss that often responds dramatically to appropriate therapy. Therefore, the distinction is important but in many cases may be difficult because such patients often present with no other nasal symptoms, and routine physical findings may be nonspecific. The purpose of this report is to characterize those aspects of the history and physical examination that will help to substantiate the diagnosis of a conductive olfactory loss. STUDY DESIGN: A retrospective, nonrandomized study of consecutive patients presenting with a primary complaint of olfactory loss. METHODS: This study reviewed 428 patients seen at a university-based taste and smell clinic from July 1987 through December 1998. Of this total, 60 patients were determined to have a conductive olfactory loss. All patients were referred specifically because of a primary chemosensory complaint. The University of Pennsylvania Smell Identification Test (UPSIT; Sensonics, Inc., Haddon Heights, NJ) was administered in all cases. RESULTS: The most commonly diagnosed etiologies of olfactory loss were head injury (18%), upper respiratory infection (18%), and nasal or sinus disease (14%). Of the 60 patients with a conductive loss, only 30% complained of nasal obstruction, whereas 58% described a history of chronic sinusitis. Only 45% reported that their olfactory loss at times seemed to fluctuate in severity. Anterior rhinoscopy failed to diagnose pathology in 51% of cases, whereas nasal endoscopy missed the diagnosis in 9%. Systemic steroids elicited a temporary reversal of conductive olfactory loss in 83% of patients who received them, offering a useful diagnostic maneuver, whereas topical steroids did so in only 25%. CONCLUSIONS: The etiology for olfactory loss can in many cases be difficult to determine, but it is important to establish prognosis and to predict response to therapy. Diagnosis requires a thorough history, appropriate chemosensory testing, and a physical examination that should include nasal endoscopy. A trial of systemic steroids may serve to verify that the loss is indeed conductive. PMID- 11192907 TI - Middle ear effusions and structure of the tympanic membrane. AB - OBJECTIVE: To study the effect of various middle ear effusions on the structure of the lamina propria of the tympanic membrane. METHODS: Sterile and infective middle ear effusions were induced by obstruction of the eustachian tube in specific pathogen-free (SPF) rats and in rats with upper airway infections (URI), respectively. The condition of the tympanic membrane was monitored at regular intervals. After varying survival times, the animals were killed and the tympanic membranes processed for light and electron microscopy. RESULTS: Sterile effusions always resulted in tympanosclerotic lesions. These lesions did not develop in the presence of primary-infected effusions. These effusions had a severe destructive effect on the lamina propria, followed by fibrosis. Generally, secondary infection did not markedly affect preexisting tympanosclerotic lesions. Moreover, calcification disappeared when re-aeration of the middle ear occurred, but the abnormal collagen depositions persisted. CONCLUSIONS: Both sterile and infective effusions result in comprehensive irreversible changes in the lamina propria of the pars tensa. The development of tympanosclerosis is confined to sterile effusions. Mechanical injury and compromised vascularization of the lamina propria are likely to be important etiological factors in the development of tympanosclerosis. PMID- 11192908 TI - Spontaneous otoacoustic emissions in humans with endolymphatic hydrops. AB - OBJECTIVE/METHODS: The origin and clinical implications of spontaneous otoacoustic emissions (SOAEs) have not been well revealed. To investigate the relationship between the ear with endolymphatic hydrops and SOAE, SOAEs were measured in 31 patients with unilateral endolymphatic hydrops and 10 volunteers with normal hearing levels that had less than 25 dB hearing level (HL) on average for five frequencies (0.25, 0.5, 1, 2, and 4 kHz). RESULTS: SOAEs were detected in 18 (58%) of the 31 ears with hydrops. In 15 hydropic ears in which the hearing levels were less than 25 dB HL on average, SOAEs were observed in 11 (73%). The results of examining the relationship between changes in hearing level after administering the glycerol test and SOAE frequency showed that four (50%) of eight hydropic ears had SOAEs that were detectable between the frequency in which hearing level improved more than 5 dB and the frequency with no hearing level change in the audiogram. In 28 contralateral ears, except for three cases of delayed endolymphatic hydrops, SOAEs were detected in 17 (61%). In 14 contralateral ears in which the hearing levels were less than 25 dB HL on average for the five frequencies noted above, SOAEs were observed in nine ears (64%). In 20 normal ears, SOAEs were detected in eight (40%). Prevalence of SOAEs in hydropic ears and contralateral ears of the patients with unilateral hydrops tended to be greater than that in normal ears; however, there was no significant statistical difference between them. CONCLUSION: The present results suggest that it is not possible to mention the characteristics of SOAE in the hydropic ear only in terms of the prevalence of SOAEs. SOAEs may occur in a specific portion of the basilar membrane corresponding to the frequency in which hearing levels improve after the glycerol test, in some cases with endolymphatic hydrops. PMID- 11192909 TI - Factors influencing the use of breast reconstruction postmastectomy: a National Cancer Database study. AB - BACKGROUND: Advances in surgical techniques and changes in our understanding of the biology of breast cancer have made immediate or early breast reconstruction a viable option for the majority of women with breast cancer. Little is known about national patterns of use of reconstruction. This study was undertaken to determine national patterns of care and factors that influence the use of breast reconstruction. STUDY DESIGN: A large convenience sample reported to the National Cancer Data Base was studied. Patients coded as undergoing mastectomy between 1985 and 1990 (n = 155,463) and between 1994 and 1995 (n = 68,348) were evaluated. The use of reconstruction in the two time periods was compared, and patient and tumor factors influencing the use of the procedure were compared. RESULTS: Between 1985 and 1990, 3.4% of mastectomy patients had early or immediate reconstruction, increasing to 8.3% in 1994-5. Patient age, income, geographic location, type of hospital where treatment occurred, and tumor stage all influenced the use of reconstruction in univariate analysis. In multivariate analysis, patients age 50 or under had a 4.3-fold greater likelihood of having reconstruction than their older counterparts. Patients with ductal carcinoma in situ were twice as likely as those with invasive cancer to have reconstruction. Family income of $40,000 or more (Odds Ratio 2.0), ethnicity other than African American (Odds Ratio 1.6), surgery in a National Cancer Institute-designated cancer center (Odds Ratio 1.4), and surgery in a geographic region other than the Midwest or South (Odds Ratio 1.3) remained significant predictors of the use of reconstruction in multivariate analysis. CONCLUSIONS: Breast reconstruction is an underused option in breast cancer management. Predictors of the use of reconstruction do not reflect contraindications to the procedure, and indicate the need for both physician and patient education. PMID- 11192910 TI - Genetic markers in sepsis. PMID- 11192911 TI - Organ allocation in the United States: where does it stand? Point. PMID- 11192912 TI - Organ allocation in the United States: where does it stand? Counterpoint. PMID- 11192913 TI - Sister Mary Joseph's sign from metastatic disease of the pancreas. PMID- 11192914 TI - Gallbladder surgery reveals Ascaris lumbricoides. PMID- 11192915 TI - Hand-assisted laparoscopic live-donor nephrectomy. PMID- 11192916 TI - In situ pedicle resection in left trisegmentectomy of the liver combined with reconstruction of the right hepatic vein to an inferior vena caval segment transpositioned from the infrahepatic portion. AB - A combination of an in situ pedicle resection of the liver and a hepatic vein reconstruction using a cranially transpositioned segment of the IVC after implantation of an ePTFE graft at the missing IVC was useful in treating a patient who suffered from a huge liver tumor involving all of the hepatic venous confluence and the IVC. Although early tumor recurrence remains an unresolved problem for such patients, a surgical approach is feasible. This technique can be justified as a therapeutic modality, not only because it improves quality of life, but also because it provides patients with an opportunity for additional treatment. PMID- 11192917 TI - Controversy: length of stay. PMID- 11192918 TI - Incisional endometriosis. PMID- 11192919 TI - Use of healthcare resources among medically and surgically treated patients with gastroesophageal reflux disease: a population-based study. AB - BACKGROUND: Gastroesophageal reflux disease (GERD) is a common disorder that may be effectively managed medically or surgically. Direct evaluations of medical resource use are needed to better understand the relative costs of these alternatives. This study compared medical care use for a group of patients receiving surgical treatment for GERD with that for a comparable group of patients receiving medical management. STUDY DESIGN: We conducted a retrospective matched cohort study of Tennessee Medicaid (TennCare) patients with GERD undergoing surgical treatment in 1996 and a group of patients who received medical therapy during the same period. Administrative TennCare data provided computerized records that could be used to identify patients and measure healthcare use. There were 7,502 people who met all of the conditions for inclusion in the study, including at least two encounters with a diagnosis of GERD. One hundred thirty-five of these who underwent fundoplication constituted the surgically treated cohort. The 250 persons in the medically treated cohort were selected randomly from the remaining nonsurgical patients and matched to the surgical cohort by age, gender, race, managed care organization, and acid suppression drug use in the baseline year. The principal outcome of interest was total use of medical resources, including prescription medication. RESULTS: The surgical and medical cohorts did not differ significantly by demographic characteristics or by baseline use of pharmaceuticals. During the baseline year the surgically treated patients were prescribed 302 (95% CI: 270-334) days ofGERD treatment and the matched medical patients were prescribed 292 (95% CI: 267-317) days of GERD treatment. Surgically treated patients used more GERD-related outpatient resources (physician visits and diagnostic testing) in the baseline year, particularly in the 3 months before operation, when they had a mean of more than four outpatient encounter-days. In the followup year, use of GERD-related pharmaceuticals decreased markedly in the surgical cohort. These patients were prescribed an average of 123 days (95% CI: 94-153) of therapy, which was only 36% of that for medical patients (339 days [95% CI: 308-370]). More than 29% of surgical patients were prescribed no GERD-related drugs in the followup year compared with 6% of the medically treated group. The mean number of inpatient days for the fundoplication procedure was 3.2 (95% CI: 2.7-3.6), with a range of 0 to 13 days. There were no differences between the two groups in other healthcare use. CONCLUSIONS: Our results show that in a 1-year period of followup, surgical treatment of severe gastroesophageal reflux disease led to a 64% postsurgical reduction in GERD medication use, with no increase in use of other medical services. PMID- 11192920 TI - The Turkish experience with curative gastrectomies for gastric carcinoma: is D2 dissection worthwhile? AB - BACKGROUND: The only possible curative treatment in gastric carcinoma is surgery, and there is still controversy surrounding the value of extended lymph node dissection. STUDY DESIGN: A retrospective cohort study was conducted in patients who underwent curative D1 or D2 resection for operable gastric carcinoma. Survival and multivariate prognostic factor analyses were carried out to determine whether dissection type was significant for outcomes, and which subgroup of patients would benefit from D2 dissection. RESULTS: Three hundred one patients who had potentially curative treatment were eligible to enter the trial. Although mortality rates were 3.1% in the D1 group and 4.3% in the D2 group (p = NS), morbidity rates in the D1 and D2 groups were 6.2% and 27.9%, respectively (p<0.05). Multivariate analysis showed that lymph node dissection type, Borrmann type of tumor, number of metastatic lymph nodes, and depth of wall invasion were the most important independent prognosticators. Five-year disease-free and overall survival rates were 19% and 36% in D1, and 49% and 54% in D2, respectively (p<0.05). After stratifying for pT and pN, the significant survival advantage with D2 was observed in subgroups of pT2, pT3 and pN1, pN2. The subset analysis showed a significant prognostic benefit with D2 dissection in patients in stages II and III-A. CONCLUSIONS: D2 dissections can be carried out with low mortality rates, but they have high morbidity rates and a survival advantage over D1 dissection of only 18%. In principle, a survival benefit with D2 is obtained especially when the tumor invades muscularis propria, penetrates serosa without invasion of adjacent structures, or metastasizes to fewer than fifteen regional lymph nodes. Data in this homogeneous population support the use of extended lymphadenectomy for selected group of patients with gastric carcinoma. PMID- 11192921 TI - Hepatic resection for hepatocellular carcinoma in the elderly. AB - BACKGROUND: Although the number of elderly people undergoing surgery for hepatocellular carcinoma (HCC) has increased because of the prolonged life expectancy rate, potential benefits of hepatectomy for elderly patients with HCC have not been fully delineated. STUDY DESIGN: Using medical records, surgical outcomes of HCC in 103 patients 70 years of age or older undergoing hepatic resection (older group) were clarified and compared with those of 283 patients younger than 70 years of age (younger group) in this retrospective study. Postresection prognostic factors were evaluated by multivariate analysis using Cox's proportional hazards model. RESULTS: There were no significant differences in postoperative complication, operative mortality, and overall hospital death rates between the two groups. Overall 3- and 5-year survival rates for the older group and the younger group were 51.0% versus 55.2%, and 42.2% versus 40.0%, respectively (p = 0.95). Disease-free 3- and 5-year survival rates for the older group and the younger group were 35.2% versus 37.6%, and 16.6% versus 24.2%, respectively (p = 0.66). Multivariate analysis revealed that the presence of liver cirrhosis and vascular invasion were independently significant factors of poor overall survival. CONCLUSIONS: Selected elderly patients with HCC benefited from resection as much as young patients, and age by itself may not be a contraindication to surgery. Postresection longterm prognosis in the elderly was determined by the presence of liver cirrhosis and vascular invasion. PMID- 11192922 TI - Extended hepatic resection: a 6-year retrospective study of risk factors for perioperative mortality. AB - BACKGROUND: Extended hepatic resection (more than four liver segments) is a major operative procedure that is associated with significant risk. The purpose of this study was to assess the impact of perioperative variables on in-hospital mortality after extended hepatectomy. STUDY DESIGN: Consecutive patients who underwent extended hepatic resection were studied. The prognostic value of 29 perioperative variables was evaluated using in-hospital mortality as the endpoint. For each variable, the odds ratio (95% confidence interval) for in hospital mortality was calculated. Those variables with a lower confidence limit > 1 were considered important risk factors. The population was stratified into categories of patients having the same number of risk factors, and mortality was estimated for each group. These data were used to develop a risk assessment algorithm. RESULTS: There were 14 deaths (6%) in 226 patients. Three preoperative variables (cholangitis, creatinine > 1.3 mg/dL, and total bilirubin > 6 mg/dL) and two operative variables (blood loss > 3 L and vena caval resection) appear to be important factors for in-hospital mortality. The mortality associated with the presence of any two of the five factors was 100% (5 of 5), and the mortality associated with the absence of these factors was 3% (6 of 191). CONCLUSIONS: Perioperative evaluation of patients undergoing extended hepatic resection should include the quantitation of mortality risk factors. The combination of any two factors among preoperative cholangitis, elevated serum creatinine, elevated serum bilirubin, high operative blood loss, and vena cava resection may carry a high mortality risk. These results require prospective validation. PMID- 11192923 TI - The effect of cyclooxygenase-2 inhibitor FK3311 on ischemia-reperfusion injury in a canine total hepatic vascular exclusion model. AB - BACKGROUND: Liver grafts from non-heart-beating donors inevitably suffer from warm ischemic injury. In these grafts, large quantities of inflammatory cytokines and arachidonic acid metabolites are induced, further aggravating injury. Cyclooxygenase (COX) is an intracellular enzyme that converts arachidonic acid into prostaglandin (PG)G2 and PGH2. COX has two isoforms: constitutive COX-1 and inducible COX-2. The aim of this study was to evaluate the effects of COX-2 inhibition by FK3311 (FK) on warm ischemic injury in a canine total hepatic vascular exclusion (THVE) model. STUDY DESIGN: Sixteen mongrel adult dogs were studied. The portal triad of the hilum and the inferior vena cava above and below the liver was clamped for 1 hour. Splanchnic decompression was achieved by active splenofemorojugular bypass. The animals were divided into two groups. FK (1 mg/kg) was administered in the FK group (n = 8), and saline was administered in the control group (n = 8). Hepatic venous blood was collected to measure serum alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase (LDH), and hyaluronic acid levels. Serum thromboxane (Tx)B2 and 6-keto-PGF1alpha levels were also measured. Hepatic tissue blood flow was estimated simultaneously. Liver specimens were harvested for histologic study and polymorphonuclear neutrophils were counted. RESULTS: Alanine aminotransferase, aspartate aminotransferase, and hyaluronic acid 2 and 6 hours after reperfusion and LDH 30 minutes and 2 and 6 hours after reperfusion were significantly (p < 0.05) lower in the FK group than in the control group. Hepatic tissue blood flow remained significantly (p < 0.05) higher in the FK group than in the control group 1, 2, and 6 hours after reperfusion. Histologic tissue damage was mild and polymorphonuclear neutrophil infiltration was significantly lower (p < 0.05) in the FK group than in the control group 1 and 6 hours after reperfusion. Thirty minutes after reperfusion, TxB2 was significantly reduced (p < 0.05) in the FK group, and 6-keto-PGF1alpha was not significantly lower. CONCLUSIONS: FK protected against hepatic warm ischemia-reperfusion injury by marked inhibition of TxA2. PMID- 11192924 TI - Surgical complications after primary nephrectomy for Wilms' tumor: report from the National Wilms' Tumor Study Group. AB - BACKGROUND: Surgical complications are a recognized morbidity of the treatment of patients with Wilms tumor. This study examines the incidence of surgical complications in the most recently completed study from the National Wilms' Tumor Study Group (NWTSG). STUDY DESIGN: The fourth National Wilms' Tumor Study (NWTS 4) enrolled 3,335 patients from August 1986 to August 1994. A random sample of 534 patients was selected from 2,290 eligible patients randomized to treatment regimens or enrolled in the followed category and treated according to NWXTSG protocol. The patient records received at the NWTSG Data and Statistical Center were analyzed for surgical complications (intraoperative and postoperative). RESULTS: Sixty-eight patients (12.7%) experienced 76 complications. Intestinal obstruction was the most common complication (5.1% of patients), followed by extensive hemorrhage (1.9%), wound infection (1.9%), and vascular injury (1.5%). The incidence of surgical complications in NWTS-4 was significantly lower than NWTS-3 (12.7% versus 19.8%, p < 0.001). There has been a marked decrease in the risk of extensive intraoperative bleeding and major intraoperative complications. Factors previously shown to be associated with an increased risk for surgical complications, together with indicators of type of hospital and surgeon specialty, were analyzed by multiple logistic regression analysis. Intravascular extension into the inferior vena cava (IVC), the atrium, or both (p = 0.02; odds ratio [OR] 3.8, 95% confidence interval [CI] 1.2, 11.8), and nephrectomy performed through a flank or paramedian incision (p = 0.02; OR 5.3, 95% CI 1.3, 22) were both associated with increased risk of complications. Tumor diameter greater than or equal to 10cm was also associated with an increased risk of surgical complications (p = 0.05; OR 2.0, 95% CI 1.0, 3.9). The risk of complications was higher if the nephrectomy was performed by a general surgeon (OR 9.0, 95% CI 1.3, 65; p = 0.03) rather than a pediatric surgeon (reference group, OR 1.0) or pediatric urologist (OR 0.7, 95% CI 0.3, 1.8). CONCLUSIONS: The incidence of surgical complications in NWTSG patients undergoing primary nephrectomy has significantly decreased over the past decade. But surgical morbidity should not be overlooked. It is important that surgeons treating young children with solid tumors are aware of their role and the potential risks encountered in removal of the primary tumor. This study found that surgical specialists who primarily treat children can perform these operations with lower surgical morbidity. PMID- 11192925 TI - Breast reconstruction--from never to now. PMID- 11192926 TI - Is this a practical approach? PMID- 11192927 TI - Ethical principles for everyone in health care. PMID- 11192928 TI - John Holter's shunt. PMID- 11192929 TI - The water of life: a century of confusion. PMID- 11192931 TI - Uterine fibroid embolization: nonsurgical treatment for symptomatic fibroids. AB - BACKGROUND: Earlier studies demonstrated the efficacy of uterine fibroid embolization (UFE). We seek to demonstrate the success of the procedure in a community hospital setting, and we attempt to identify patients likely not to benefit from embolization, if possible, before the procedure. STUDY DESIGN: The study followed all women treated with UFE for menorrhagia or postmenopausal bleeding at a community hospital between 1997 and 1999. Relief of symptoms, ultrasound changes, and complications were documented. Six months after the procedure, analysis was performed on ultrasound and interview data from patients who underwent UFE. A smaller number of patients has been followed for 12 months and were available for the analysis. We examined characteristics of patients and procedures performed in an attempt to identify likely failures of treatment. We calculated complication and failure rates based on the entire group of patients. RESULTS: From 183 patients who applied for UFE, 16 were excluded because ofpathologic conditions found during preembolization evaluation; 167 women had an embolization, 163 were successfully embolized bilaterally, and 4 were embolized unilaterally because of technical failure. Eighty-eight percent of the patients (147 of 167 patients) reported an improvement or stabilization of symptoms 6 months after UFE. Forty-six patients followed for 12 months experienced myoma shrinkage of 37% (a significant shrinkage over 6 months, p < 0.001), and total uterine volume decreased 52%. Analysis of shrinkage data revealed no demographic or procedure variable associated with shrinkage. Six patients underwent hysterectomy (3.5%) after embolization, one as a result of postprocedure infection. Pain in the first 24 hours postprocedure affected almost all patients. Five percent of the patients passed submucous myomata after UFE; all these patients at risk were identified at preembolization hysteroscopy. Four patients experienced premature menopause after embolization early in the study. There were three criteria for failure, of which a patient had to meet only one: hysterectomy, < 10% shrinkage ofmyoma 6 months after UFE, or worsening symptoms after UFE. No variables of age or size of the uterus could be shown to predict failure. Patients who had undergone earlier pelvic surgery were more likely to fail UFE (p = 0.012). CONCLUSIONS: Uterine fibroid embolization, an alternative treatment for myomas, offering low morbidity, can be performed in a community hospital setting. Eighty-eight percent of patients reported improvement or stabilization of symptoms. Total uterine volume decreased an average of 49% at 6 months after embolization. Shrinkage was unaffected by the size of the uterus, myoma, or patient characteristic before UFE. Longterm followup study reveals a significant continuing shrinkage of total uterine volume and myomata at 12 months. There has been no regrowth of fibroids. Earlier surgery was a factor predicting failure of UFE in our series. The risks to future fertility were small. PMID- 11192930 TI - The effects of postinjection massage on the sensitivity of lymphatic mapping in breast cancer. AB - BACKGROUND: The technique of lymphatic mapping and sentinel lymph node (SLN) biopsy is rapidly becoming the preferred method of staging the axilla of the breast cancer patient. This report describes the impact of postinjection massage on the sensitivity of this surgical technique. STUDY DESIGN: Lymphatic mapping at the H Lee Moffitt Cancer Center is performed using a combination of isosulfan blue dye and Tc99m labeled sulfur colloid. Data describing the rate of SLN identification and the node characteristics from 594 consecutive patients were calculated. Patients who received a 5-minute massage after injection of blue dye and radiocolloid were compared with a control group in which the patients did not receive a postinjection massage. RESULTS: When compared with controls, the proportion of patients who had their SLN identified using blue dye after massage increased from 73.0% to 88.3%, and the proportion of patients who had their SLN identified using radiocolloid after massage increased from 81.7% to 91.3%. The overall rate of SLN identification increased from 93.5% to 97.8%. The proportion of nodes that were stained blue among those removed increased from 73.4% to 79.7% after massage. CONCLUSIONS: As experience increases with this new procedure, the surgical technique of lymphatic mapping continues to evolve. The addition of a postinjection massage significantly improves the uptake of blue dye by SLNs and may also aid in the accumulation of radioactivity in the SLNs, further increasing the sensitivity of this procedure. PMID- 11192932 TI - The fight against rheumatism: from willow bark to COX-1 sparing drugs. AB - Man has been fighting rheumatism for thousands of years. Early therapy began with the use around the world of decoctions or extracts of herbs or plants such as willow bark or leaves. Most or all of these turned out to contain salicylates. The first record was about 3,500 years ago in the Ebers papyrus. Hippocrates, Celsus, Pliny the Elder, Dioscorides and Galen all recommended decoctions containing salicylate for rheumatic pain. A country parson, the Reverend Edward Stone of Chipping Norton in Oxfordshire, made the first "clinical trial" of willow bark (1). He was surprised by its bitter taste, which reminded him of cinchona bark (containing quinine), then being used to treat malaria. He harvested a pound of willow bark, dried it, pulverized it and dispersed it in tea, small beer or water. He found in 50 patients that doses of 1 dram (1.8g) cured their fever. He concluded "I have no other motives for publishing this valuable specific, than that it may have a fair and full trial in all its variety of circumstances and situations, and that the world may reap the benefits accruing from it". Salicylic acid was chemically synthesised in 1860 by Kolbe in Germany and its ready supply led to even more extended usage as an external antiseptic, as an antipyretic and in the treatment of rheumatism. PMID- 11192933 TI - Regulation of cyclooxygenase isoforms in the renal thick ascending limb: effects of extracellular calcium. AB - We previously showed that primary cultures of mTAL cells express cyclooxygenase 2 (COX-2) when challenged with tumor necrosis factor alpha (TNFalpha) or phorbol myristate acetate (PMA). Moreover, expression of COX-2 was linked to decreases in TNFalpha-mediated 86Rb uptake, an in vitro correlate of natriuresis. mTAL cells in primary culture express calcium sensing receptor (CaR), a G-protein coupled receptor that senses changes in extracellular calcium concentration and ultimately increases intracellular calcium concentration ([Ca2+]i) and protein kinase C (PKC) activity. PGE2 synthesis by mTAL cells increases in a dose- and time-dependent manner after exposure of these cells to extracellular Ca2+. Similar effects were observed when cells were challenged with the CaR-selective agonist, poly-L-arginine. These data suggest that intracellular signaling mechanisms initiated via activation of CaR contribute to mTAL PGE2 synthesis. As TNF production is calcium-sensitive in some cells types, we postulate that these effects involve the regulation of COX-2 expression via a TNF-dependent mechanism. The functional implications of these studies relate to a cytokine-mediated mechanism that contributes to salt and water balance, and suggests that small changes in Ca(2+)o may contribute to the regulation of these events. The possibility that the effects of Ca(2+)o involve activation of CaR suggests that novel calcimimetic molecules might be useful in conditions, such as hypertension or other conditions, in which manipulation of extracellular fluid volume provides beneficial effects. PMID- 11192934 TI - Trans-arachidonic acids: new mediators of inflammation. AB - Inflammation and many other pathological processes lead to increased production of free radicals that target critical macromolecules such as proteins, DNA and lipids. Structural modifications of these molecules, induced by free radicals, typically result in alterations of vital biochemical processes. Hydroxyl radical initiated lipid peroxidation is known to generate a variety of toxic oxidized lipids, many of which originate from polyunsaturated fatty acids esterified to cellular membrane phospholipids. Recent interests have focused on a group of lipids known as isoeicosanoids that are formed from peroxidation of arachidonic acid, and share structural similarity to enzymatically-derived prostaglandins and leukotrienes. However, little is known about lipid peroxidation processes initiated by nitrogen free radicals. NO2 is a toxic free radical and an abundant urban air pollutant, which is also generated in vivo from oxidations of nitric or nitrite and decomposition of peroxynitrite. The NO2-induced lipid peroxidation mechanisms involving arachidonic acid have not been characterized. Described here is the isomerization of arachidonic acid, a new process induced by NO2, which leads to a mixture of trans-arachidonic acids. We observed that the levels of trans-arachidonic acids in rat plasma increased following infusion of bacterial endotoxin; therefore, the isomerization of arachidonic acid is likely to occur in vivo by a mechanism involving NO2. PMID- 11192935 TI - Paracetamol-inhibitable COX-2. AB - Although paracetamol potently reduces pain and fever, its mechanism of action has so far not been satisfactorily explained. It inhibits both COX-1 and COX-2 weakly in vitro, but reduces prostaglandin synthesis markedly in vivo. In mouse macrophage J774.2 cells, COX-2 induced for 48 hr with high concentrations of NSAIDs is more sensitive to inhibition with paracetamol than endotoxin-induced COX-2. In the rat pleurisy model of inflammation, a second peak of COX-2 protein appears 48 hr after administration of the inflammatory stimulus, during the resolution phase of the inflammatory process. Inhibition of the activity of this late-appearing COX-2 with indomethacin or a selective COX-2 inhibitor, delays resolution and the inflammation is prolonged. Cultured lung fibroblasts also express COX-2 activity after stimulation with IL-1beta which is highly sensitive to inhibition with paracetamol. Thus, evidence is accumulating for the existence of a COX-2 variant or a new COX enzyme which can be inhibited with paracetamol. PMID- 11192936 TI - Changes in renal autacoids in aged human hypertensives. AB - The aging process determines several modifications of the kidney, that, however, do not provoke any dysfunction in normal conditions. But in the elderly--in the presence of stressful situations and particularly when adrenergic activation is present--the kidney is more vulnerable than in the young, and renal failure may arise. Variations typical of the aging kidney are accelerated when hypertension overlaps the physiological renal process, because both senescence and hypertension weight on the same structures, i.e. glomeruli. We studied renal hemodynamic adaptation capacity both in the healthy elderly and in patients affected by isolated systolic hypertension, in an acute experiment which requires the application of a mental stress-induced adrenergic activation. In hypertensive patients we have already demonstrated a total lack of renal adaptation capacity. In fact, while the elderly normotensives react with a prolonged and pronounced vasoconstriction, in those with isolated systolic hypertension, adrenergic activation induces a passive renal vasodilation and glomerular hyperfiltration. The anomalous adaptation capacity of renal hemodynamics is probably due to an impairment in the paracrine response of renal vasculature. Indeed in the hypertensive elderly, unlike in the normotensive one, no variations of autacoid production occur during the adrenergic activation. Following on from this, pattients affected by isolated systolic hypertension passively suffer the many hypertensive peaks which characterize their every day life. The altered renal autoregulation of the elderly with isolated systolic hypertension may explain the accelerated glomerulosclerosis and the greater incidence of renal damage and end stage renal disease which characterize this condition. These aspects underline the primary role of the antihypertensive treatment of isolated systolic hypertension, not only for the prevention of cardiovascular mortality but also of renal damage and/or end-stage renal disease. PMID- 11192937 TI - Clinical pharmacology of eicosanoids, nicotine induced changes in man. AB - Smoking is an important risk factor for respiratory and cardiovascular diseases. The role of numerous chemical, partly uncharacterised compounds existing in tobacco smoke is not known. (-)-Nicotine, its stereoisomer (+)-nicotine and main metabolite cotinine are biologically active compounds influencing e.g. catecholamine and eicosanoid systems. The precise mechanisms are not well known. The purpose of the present study consisting of a PhD thesis (11) and five original papers was to investigate the in vitro effects of nicotine isomers and cotinine on eicosanoid production in polymorphonuclear leukocytes, platelets and whole blood in vitro, and to clarify the effects of smoking without and with nicotine substitution on eicosanoid production in vivo and ex vivo. It was found that all the tested compounds modulated blood cell eicosanoid synthesis. Nicotine isomers and cotinine increased PGE2 but decreased TXB2, LTB4 and LTE4 synthesis in vitro. Eicosanoid synthesis in vivo and ex vivo was higher in smokers (n = 60) than in non-smoking controls (n = 20). This may contribute to the harmful cardiovascular effects of smoking. Cessation of smoking without, but not with, nicotine substitution reduced eicosanoid synthesis measured ex vivo as whole blood production or in vivo as urinary excretion of eicosanoid metabolites after 3, 7 and 14 days. Thus long-term nicotine substitution diminishes the beneficial effects of smoking cessation. PMID- 11192938 TI - Anti-microinflammatory lipid signals generated from dietary N-3 fatty acids via cyclooxygenase-2 and transcellular processing: a novel mechanism for NSAID and N 3 PUFA therapeutic actions. AB - Aspirin therapy inhibits prostaglandin biosynthesis; yet via acetylation of cyclooxygenase 2 (COX-2) it leads to bioactive lipoxins epimeric at carbon 15 (15 epi-LX, also termed aspirin-triggered lipoxin or ATL). Here, we review our findings indicating that inflammatory exudates from mice treated with omega-3 PUFA and aspirin (ASA) generate a novel array of bioactive lipid signals. Also, human endothelial cells, both HUVEC and microvascular, with upregulated COX-2 and treated with ASA converted C20:5 omega-3 to 18R-hydroxyeicosapentaenoic acid (HEPE) and 15R-HEPE. Human PMN activated with serum treated zymosan (STZ) utilized each of these R-HEPEs to generate novel classes of trihydroxy-containing mediators including 5-series 15R-LX and 5,12,18R-triHEPE. The novel products were potent inhibitors of human PMN transendothelial migration and infiltration of PMN in dorsal air pouches in vivo. In addition to ASA, both acetaminophen and indomethacin also permitted 18R-HEPE and 15R-HEPE generation with recombinant human COX-2 as well as omega-5 and omega-9 oxygenations of other fatty acids that act on leukocytes, platelets and endothelial cells. These findings establish new transcellular routes for producing arrays of lipid mediators via COX-2-NSAIDs and cell-cell interactions that impact microinflammation. Moreover, they provide novel mechanism(s) that could underlie the many reported therapeutic benefits of omega-3 dietary supplementation of interest in inflammation, cancer, and vascular disorders. PMID- 11192939 TI - Selective inhibition of arachidonic acid epoxidation in vivo. AB - Cytochrome P450 (CYP)-derived arachidonic acid metabolites, including epoxyeicosatrienoic acids (EETS) and 20-HETE, have been implicated in the regulation of renal function and vascular tone. Studying the function of specific CYP arachidonate metabolites has been hampered due to lack of selective inhibitors and difficulty in their solubilization. We have identified MS-PPOH as a potent and selective inhibitor of CYP-catalyzed arachidonate epoxidation in vitro. We used 2-hydroxypropyl-beta-cyclodextrin as a vehicle in order to administer MS-PPOH in vivo. One hour after administration, MS-PPOH (5 mg, IV bolus) significantly inhibited arachidonic acid epoxidation in rat renal cortical microsomes (vehicle-282 +/- 12 pmol/mg/min, MS-PPOH-206 +/- 10 pmol/mg/min, p < 0.05) but had no effect on 20-HETE formation (vehicle-383 32 pmol/mg/min, MS-PPOH 367 +/- 9 pmol/mg/min). The inhibitory effect lasts at least for 6 hours. There was no inhibition of 20-HETE synthesis at any time point. We also examined the effect of MS-PPOH on renal excretiry function. Three hours after MS-PPOH administration to anesthetized rats, urine flow rate became significantly higher (vehicle-275 +/- 16 microl/hour, MS-PPOH-406 +/- 44 microl/hour, p < 0.05). Sodium excretion rate was also significantly higher (vehicle-28.7 +/- 4 micromol/hour, MS-PPOH-63.3 +/- 10 micromol/hour, p < 0.05) but potassium excretion rate was not affected (vehicle-65.5 +/- 5 micromol/hour, MS-PPOH-79.2 +/- 2 micromol/hour). These results suggest that MS-PPOH may be useful as a selective inhibitor of CYP-catalyzed arachidonic acid epoxidation in vivo, and implicate EETs and anti-diuretic and anti-natriuretic in the regulation of renal function. PMID- 11192940 TI - Isoprostanes in atherosclerosis. AB - Isoprostanes (IP) are a new family of compounds formed during oxidation injury. 8 epi-prostaglandin (PG) F2alpha, a vasoconstrictory and mitogenic substance, is increased in hyperlipidemia in blood and urine as well as at the vascular level in the intima, in particular along foam cells. Similarly, cigarette smoking is associated with an immediate increase in 8-epi-PGF2alpha and a quick drop after quitting. Also diabetes and even the more a combination of risk factors (for the development of atherosclerosis) results in increased 8-epi-PGF2alpha in various compartments. Others, such as sex, age, hypertension and obesity were of minor influence. These findings further indicate, that in-vivo oxidation injury as reflected by increased IP may play a relevant role in atherogenesis. IP may serve as useful markers to assess oxidation injury at a local level. PMID- 11192941 TI - Thrombolysis by thienopyridines and their congeners. AB - We propose that anti-platelet thienopyridines, such as ticlopidine or clopidogrel, are thrombolytic owing to endothelial release of prostacyclin (PGI2) and tissue plasminogen activator (t-PA). In this study we used anaesthetised Wistar rats with extracorporal circulation in which arterial blood superfused thrombi which adhered to a strip of collagen. Weight of thrombi was continuously monitored. When administered intravenously, clopidogrel or its R enantiomer deprived of anti-platelet action, both at doses of 3 mg x kg(-1), produced lost in weight of thrombi by 14.1 +/- 1.3% or 16.0 +/- 1.4% (n = 9), and at doses 10 mg x kg(-1) by 28.3 +/- 2.3% or 30.4 +/- 1.9% (n = 8), respectively. Maximum of thrombolysis occurred 30-45 min following the drug administration. Ticlopidine at a dose of 30 mg x kg(-1) reduced weight of thrombi by 33.7 +/- 1.7% (n = 32). Thrombolytic action of ticlopidine was accompanied by a rise in 6!keto-PGF1alpha blood levels from 0.42 +/- 0.10 to 1.58 +/- 0.29 ng x ml(-1) and t-PA antigen plasma levels from 4.70 +/- 1.00 to 12.90 +/- 1.15 ng x ml(-1) (n = 7). Five out of eleven tested thienopyridine congeners with pyrimidine or pyrimidinone instead of pyridine rings had thrombolytic potencies similar to that of clopidogrel (ED30s at a range of 6.2-11.4 mg x kg(-1)). A substantial increase in thrombolytic potency (ED30s at a range of 0.3-2.1 mg x kg(-1)) was observed for congeners in which thienyl ring was condensed with an additional cyclopentyl, cyclohexyl or cycloheptyl structures or in which thienopyridine complex was replaced for a pyridopyrimidine one. We claim that thienopyridines, independently of their delayed anti-platelet action, do produce immediate thrombolysis in vivo. This new activity emulates capacity of their native, non-metabolised molecules to release prostacyclin and tissue plasminogen activator. We have also shown that structural changes in molecules of thienopyridines may intensify their thrombolytic potency. PMID- 11192942 TI - The protective role of nitric oxide in the brain ischemia. AB - A role of nitric oxide in ischemia/reperfusion (I/R) injury of brain in normotensive (Sprague-Dowley rats, SD) and stroke-prone spontaneously hypertensive rats (SHR-SP) was studied. Cerebral ischemia was produced in rats by occlusion of the middle cerebral artery (MCA). NO and O2- releases in the brain in response to MCA occlusion followed by reperfusion were simultaneously monitored (2h) using electrochemical microsensors. The size of infarct was evaluated in the course of I/R from images of brain slices stained with 2,3,5 triphenyltetrazolium chloride. Similar patterns of NO and O2- releases were exhibited for SD and SHR-SP rats in the entire course of the experiments. However, the concentration of NO release was significantly lower during I/R in SHR-SP than in SD rats (the maximal NO concentration was 2.61 +/- 0.22 micromol/L for SD and 1.51 +/- 0.16 micromol/L for SHR-SP rats; *P < 0.01). In contrast, the concentration of O2- release during cerebral ischemia was significantly higher in SHR-SP than SD rats (the maximal increase was 122 +/- 24 nmol/L for SD and 220 +/ 44 nmol/L for SHR-SP rats; *P<0.01). The infarct sizes revealed in the course of I/R were larger in SHR-SP than SD rats (1.8 +/- 0.4% vs. 1.1 +/- 0.4% at 30 min., 2.84 +/- 0.8% vs. 2.21 +/- 0.6% at 100 min. and 9.20 +/- 1.1% vs. 5.8 +/- 0.6% at 180 min. ofthe brain weights, respectively; *P < 0.01 for each time-point). These studies indicate that nitric oxide plays a protective role during I/R and deficiency of NO in SHR-SP rats is due to excess of O2- production. The deficiency in NO concentration correlates positively with the increase of cerebral I/R injury. PMID- 11192943 TI - Losartan inhibits the adhesion of rat platelets to fibrillar collagen--a potential role of nitric oxide and prostanoids. AB - The aim of the study was to evaluate the effect of losartan on rat platelet adhesion to fibrillar collagen. Washed platelets were counted before and after 15 minutes incubation with collagen (50 microg/ml) and the percentage of adhering platelets was calculated as the index of their adhesion. When the platelets were incubated with collagen 40.8 +/- 0.3% of the platelets adhered. Losartan produced a dose dependent decrease in a number of adhering platelets both when the drug was administered to the animals ex vivo at doses of 3, 10 and 30 mg/kg (p < 0.01 0.001) or was added to the preparation of washed platelets in vitro in concentrations of 10(-8)-10(-5) M (p < 0.01-0.001). In the next step of the study we assessed the influence of L-NAME (10 mg/kg ex vivo, 30 microM in vitro) and indomethacin (2.5 mg/kg ex vivo, 30 microM in vitro) on the antiadhesive effect of losartan (10 mg/kg ex vivo, 10(-6) M in vitro). Blockade of nitric oxide synthase with L-NAME partially reversed the antiadhesive effect of losartan both ex vivo and in vitro. Indomethacin diminished the inhibitory effect of losartan on platelet adhesion when administered ex vivo, but it failed to modify this parameter when added to the suspension of platelets in vitro. In conclusion, losartan reduces platelet adhesion to fibrillar collagen in a dose-dependent manner. The observed action of losartan seems to be mediated mainly by endothelium- and platelet-derived nitric oxide. PMID- 11192944 TI - Antiplatelet action of losartan involves TXA2 receptor antagonism but not TXA2 synthase inhibition. AB - Various AT1 receptor antagonists including losartan are known to inhibit human platelet activation by antagonising TXA2/PGH2 receptors (TP receptors). Presently, we check a hypothesis that losartan, an imidazole derivative in contrast with valsartan, a non-imidazole compound, may inhibit human platelet activation also through inhibition of TXA2 synthesis. Inhibitory action of losartan (2-n butyl-4-chloro-5-hydroxymethyl-1-beta(2'-(1H-tetrazol-5yl)biphenyl 4-yl)methyl] imidazole), its active metabolite EXP 3174 (2-n-butyl-4-chloro-1 beta (2-(1H-tetrazol-5-yl) biphenyl-4-yl) methyl]imidazole-5-carboxylic acid) and valsartan ((S)-N-valeryl-N-(beta2'-(1H-tetrazol-5-yl)biphenyl-4 yl]methyl]valine), on collagen-induced platelet aggregation and TXA2 generation was compared to effects achieved by each compound on U46619-induced aggregation in aspirinized platelets. Losartan and aspirin inhibited collagen-induced platelet aggregation with approximately the same potency, whereas EXP 3174 and valsartan showed much weaker antiplatelet effects. Interestingly, losartan, EXP 3174 and valsartan displayed similar potencies as inhibitors of U46619-induced aggregation in asprinized platelets as in collagen-induced aggregation in non aspirinized platelets. None of the above three AT1 antagonists, up to a concentration of 300 microM, did influence collagen-induced TXA2 synthesis in human platelets. In conclusion, antiplatelet effects of AT1 antagonists, irrespective of the presence or absence of non-condensed imidazole in their chemical structure, involve antagonism of TP receptors but not inhibition of TXA2 synthesis in platelets. PMID- 11192945 TI - The role of platelet-activating factor (PAF) antagonists and nitric oxide in cardiac actions of PAF. Electrophysiological and morphological study. AB - Electrophysiological and ultrastructural effects of platelet-activating factor (PAF) antgonists, WEB 2086 and BN 52021 were compared in isolated guinea-pig hearts preparations. We studied the possible role of nitric oxide (NO) in electromechanical actions of PAF. Isometric twitches and intracellular action potentials (APs) were recorded from guinea-pig right ventricular papillary muscles and left atria. For electron microscopic study the hearts were perfused according to Langendorff technique. WEB 2086 (5 x 10(-9)-5 x 10(-7) M) significantly shortened the duration of atrial AP without changing the ventricular one, however, BN 52021 decreased both of them. The shortening of atrial and ventricular AP duration (APD) by both PAF antagonits were abolished by 4-aminopyridine (10(-3) M), a blocker of one type of K+ channels (IKto). Glibenclamide (10(-6) M) the blocker of ATP-dependent K channels prevented the shortening effect of BN 52021 (10(-6) M) on ventricular APD. Electron microscopic study of myocardial samples from hearts subjected to 30 min hypoxia/reoxygenation showed intracellular oedema, intramitochondrial swelling and fragmentation of mitochondrial christae, separation of intercalated disc. Pretreatment with WEB 2086 (5 x 10(-7) M) warded off nearly all damage caused by hypoxia/reoxygenation. Both WEB 2086 and NO synthase inhibitor NG-nitro-L-arginine methyl esther (L NAME) (10(-3) M) abolished the negative inotropic effect of PAF (10(-7), 10(-6) M). L-NAME prevented the shortening of APD induced by 10(-7) M PAF. These results suggest that PAF may be responsible for myocardial ischemia and the beneficial effects of PAF antagonists in this pathological process could be due to their possible K+ channel stimulator property. These data support the possibility that NO contributes to the cardiac electromechanical alterations induced by PAF. PMID- 11192946 TI - Helicobacter pylori, gastrin and cyclooxygenases in gastric cancer. AB - BACKGROUND: Tumors arising in the stomach have worldwide distribution and the infection with Helicobacter pylori (HP) has been implicated in causation of this disease. The HP discovery, which is considered as the greatest advance of gastroenterology at the dawn of 3rd millennium, is accompanied by hypergastrinemia, which seems to play a key role in gastric cancerogenesis but no study was undertaken to assess the relationship between the HP infection and coexpression of gastrin and cyclooxygenases (COX), the rate limiting enzymes in the eicosanoids production. AIMS: Since gastrin is recognized as a effective gastric mitogen, it could be capable to induce COX-2, a potent tumor growth promoting and angiogenic factor, we decided 1) to compare the seroprevalence of HP and its cytotoxic protein, CagA, in gastric cancer patients with those in age- and gender-matched controls; 2) to determine the gene expression of gastrin and its receptors (CCK(B)-R) in gastric cancer, 3) to assess the plasma levels, gastric lumen and tumor tissue contents of gastrin and 4) to examine the mRNA and enzyme protein expression of COX-1 and COX-2 in cancer tissue and intact gastric mucosa before and after HP eradication. MATERIAL AND METHODS: The trial material included 20 patients with gastric cancers and 100 age- and gender-matched controls. Anti-HP and anti-CagA IgG seroprevalence was estimated by specific antisera using ELISA tests. Gene expressions of gastrin, CCK(B)-R, COX-1 and COX 2 was examined using RT-PCR with GAPDH as a reference and employing Western blot for COX-2 expression, while gastrin was measured by RIA. RESULTS: The seroprevalence of HP, especially that expressing CagA, was significantly higher in gastric cancers than in controls. Both gastrin and CCK(B)-R mRNA were detected by RT-PCR in the cancer tissue and similarly COX-2 mRNA and protein were found in most of cancers and in the HP infected antral mucosa but not in HP eradicated patients in whom only cancer tissue but not gastric mucosa expressed COX-2. The gastric cancer tissue contained 20 times more of immunoreactive gastrin than the HP infected antral gastric mucosa and following HP eradication the gastrin content in the tumor and antrum showed a marked and significant reduction. No significant change in CCK(B)-R expression was noticed before and after HP eradication in the tumor and the corpus mucosa. CONCLUSIONS: 1). Gastric carcinoma coexpresses gastrin, its receptors (CCK(B)-R), and COX-2; 2) HP infection may contribute to gastric cancerogenesis via gastrin andCOX-2 that may account for the stimulation of tumor growth, angiogenesis, and reduction in apoptosis 3) HP positive patients developing gastric cancer should be considered for HP eradication to reduce the HP provoked hypergastrinemia and COX-2 overexpression in the tumor tissue. PMID- 11192947 TI - Involvement of cyclooxygenase (COX)-2 products in acceleration of ulcer healing by gastrin and hepatocyte growth factor. AB - Ulcer healing involves expression of various growth factors including hepatocyte growth factor (HGF) at the ulcer margin and the rise in plasma gastrin but the effects of locally applied HGF and gastrin, which are known to act as trophic factors for the gastric mucosa, with or without neutralizing antibodies against HGF and gastrin or COX-1 and COX-2 inhibitors on ulcer healing and the expression of cyclooxygenase (COX)-1 and COX-2 during this healing have been little studied. Rats with gastric ulcers induced by serosal application of acetic acid (ulcer area 28 mm2) received a submucosal injection of either: 1)vehicle (saline), 2) HGF and 3) gastrin with or without neutralizing antibodies against HGF and gastrin or treatment with indomethacin (2 mg/kg-d i.p.), a non-specific inhibitor of COX, or NS-398 (5 mg/kg-d i.g.) and Vioxx (10 mg/kg-d i.g.), both highly specific COX-2 inhibitors. Each growth factor and specific antibodies against HGF and gastrin (100 ng/100 microl each) were injected just around the ulcer immediately after ulcer induction and this local application was repeated at day 2 following anesthesia and laparotomy. At day 13 and 21, the area of ulcers was determined by planimetry, the gastric blood flow (GBF) at ulcer margin was examined by H2-gas clearance technique and mucosal generation of PGE2 and the expression of COX-1 and COX-2 mRNA in the non-ulcerated and ulcerated gastric mucosa was analyzed using RT-PCR. The gastric ulcers healed progressively within 21 days and this effect was accompanied by significant increase in the GBF at the ulcer margin and expression of COX-2 mRNA and COX-2 protein at the ulcer area. Treatment with HGF and gastrin significantly accelerated the rate of ulcer healing and raised GBF at ulcer margin causing further significant upregulation of COX-2 mRNA and COX-2 protein (but not of COX-1 mRNA ) in the ulcerated mucosa. The upregulation of COX-2 mRNA induced by HGF was significantly attenuated by the concurrent local treatment with antibody against this growth peptide. Indomethacin and both COX-2 inhibitors significantly prolonged the ulcer healing, while suppressing the generation of PGE2 in non-ulcerated and ulcerated gastric mucosa and the GBF at ulcer margin. The acceleration of ulcer healing by HGF and gastrin and accompanying rise in the GBF at ulcer margin were significantly attenuated by the concurrent treatment with indomethacin or NS-398 and Vioxx. HGF injections produced a significant rise in the plasma gastrin levels and this was significantly attenuated by the cotreatment with NS-398. We conclude that 1) neutralization of HGF and gastrin by their specificantibodies delays ulcer healing due fall in the microcirculation around the ulcer and a decrease in the COX-2 expression, 2) COX-2 derived prostaglandins may play an important role in acceleration of the ulcer healing by various growth factors including HGF and gastrin, 3) enhancement of the local pool for growth factors such as HGF and gastrin at the ulcer site could offer a new modality for treatment of gastric ulcer. PMID- 11192948 TI - Sedation in outpatient bronchoscopy. AB - Bronchoscopy is a procedure that is likely to provoke anxiety as the patient is surrounded by monitoring and bronchoscopy equipment, and care is administered by strangers who perform intimate, invasive, and sometimes, painful procedures. Sedation is needed, therefore, to allay anxiety and reduce stress, improve patient comfort and co-operation, provide amnesia and facilitate the bronchoscopic procedure. In this review we try to summarize the current knowledge on currently used sedation protocols with special reference to the commonly used pharmacological agents. We believe sedation should be used routinely in fiberoptic bronchoscopy in order to achieve a safe and pleasant procedure for both the patient and the pulmonologist. PMID- 11192949 TI - Ventilatory response to CO2 re-breathing before and after nocturnal nasal intermittent positive pressure ventilation in patients with chronic alveolar hypoventilation. AB - Long-term nocturnal nasal intermittent positive pressure ventilation (NIPPV) has beneficial effects on daytime PaCO2 in patients with chronic alveolar hypoventilation. Our aim was to investigate if these beneficial effects are related to improved respiratory drive as measured by ventilatory response to CO2. In 17 hypoventilated patients (mean age 62 years) we obtained daytime arterial blood gases, nocturnal transcutaneous oxygen saturation, nocturnal transcutaneous PaCO2 ventilatory response to CO2 re-breathing, spirometry and indices of respiratory muscle strength before and after 9 months of NIPPV. Patients served as their own controls. After 9 months of NIPPV day-time PaCO2 decreased from 7.1 kPa to 6.3 kPa, (P<0.001) and PaO2 increased from 8.1 kPa to 9.3 kPa, (P<0.01). The changes in morning and daytime PaCO2 and in nocturnal transcutaneous oxygen saturation were significantly correlated to the changes in several variables derived from the ventilatory response to CO2 re-breathing. In patients with substantial improvement in daytime PaCO2 we found significant improvements in ventilatory response to CO2 re-breathing. The present study confirms the beneficial effect of long-term NIPPV on daytime arterial blood gases. The results are consistent with the hypothesis that the improvement of daytime PaCO2 is related to improved respiratory drive observed after NIPPV. PMID- 11192950 TI - Experience of totally implantable venous access devices (TIV ADs) in adults with cystic fibrosis over a 13-year period. AB - Totally implantable venous intravenous access devices (TIVADs) have an essential role in the frequent delivery of antibiotics in cystic fibrosis (CF) patients. This study at the Royal Brompton Hospital (RBH) reports the experience of TIVADs in patients attending the RBH adult CF unit implanted at the RBH and elsewhere over a 13-year period. The case notes of adult CF patients who had undergone TIVAD insertion were reviewed retrospectively. The patients were divided into those who had the insertion carried out at the RBH and those who had the device inserted elsewhere. All devices were cared for the at the RBH. A total of 115 devices in 74 patients were reviewed. The median duration of function of 109 devices was 1429 days (range 2-3989) or 3.9 years, with a total exposure of 91,188 days or 249.8 years. There was no significant difference between devices inserted at the RBH and those inserted elsewhere (P= 0.59). Thirty-four patients had devices installed without complications. Forty patients had complications in 62 devices. The incidence of complications was 34.5% at the devices inserted at RBH and 73.7% elsewhere (P<0.001). Of the 115 devices, mechanical complications occurred in 42 (36%) with a median time of diagnosis of 373 days (range 1-2554), infectious complications occurred in 16 (14%), with a median time of diagnosis of 413 days (range 40-2556) and symptomatic venous thrombosis occurred in four (3.5%). RBH-inserted devices had significantly fewer mechanical complications (P<0.001) compared with those inserted elsewhere. The group as a whole had fewer infectious complications than in most other reported series. We conclude that TIVADs provide effective and long-term intravenous access and have fewer complications if they are inserted and cared for at a centre with special expertise in their insertion and management. PMID- 11192951 TI - Effects of anti-reflux surgery on chronic cough and asthma in patients with gastro-oesophageal reflux disease. AB - This two-group prospective study evaluated the effect of anti-reflux surgery (fundoplication) on 24 patients with severe gastro-oesophageal reflux disease (GORD) and concomitant asthma (n=13) or chronic cough (n=11). Twenty-four hour oesophageal pH monitoring and lung function tests (FEV1, FVC) were done before and within 1 year after anti-reflux surgery. A diary was kept by the patient during the 4-week period prior to surgery and during 4-week periods 6 and 12 months postoperatively, with daily monitoring of peak expiratory flow rate, respiratory and reflux symptoms and medication. In non-asthmatic patients, coughing was reduced by 47% and 80% during the day and night, respectively, 12 months after surgery (P < 0.01). Concomitant hoarseness and expectoration were also significantly reduced (P<0.05). No effect on lung function was seen. In patients with asthma, small, non-significant reductions in asthma symptom scores and consumption of rescue medication were seen. Twenty-two patients were completely free from their GORD symptoms after surgery. In conclusion, anti reflux surgery in patients with GORD had a more favourable effect on concomitant cough than concomitant asthma. PMID- 11192952 TI - Role of spirometric and arterial gas data in predicting pulmonary complications after abdominal surgery. AB - The aim of this study was to evaluate the predictive value of preoperative spirometric and arterial gas data on severe pulmonary complications (PC) after elective abdominal surgery. We retrospectively studied 480 patients, 254 males and 226 females, mean (SD) age 63 (11) years, at risk for PC according to standardized criteria, who underwent laparotomy for resection of gallbladder for gallstones (44% of patients), resection of colon, rectum or stomach for malignant tumours (37%), and other abdominal surgery (19%). The overall incidence of postoperative PC was 18%. In a logistic regression analysis adjusted for smoking habit and clinical history of chronic bronchitis, FEV1<61% of predicted [odds ratio (OR)=16.86, 95% confidence interval (95%CI)=5.62-50.58] and PaO2<9.33 kPa (OR=6.42, 95%CI=2.48-16.61) were the main determinants of PC. Ischaemic heart disease (OR=3.44, 95%CI=1.08-10.93), operation for malignant tumours (OR=3.24, 95%CI=1.75-6.00) and age (OR=1.04, 95%CI=1.00-1.08) were also independent predictors of PC. Patients with moderate-to-severe airway obstruction combined with hypoxaemia had a significant higher risk of PC in comparison with patients with a normal respiratory pattern. Taking into account age, type of operation, and comorbidity, a preoperative respiratory functional assessment could be useful in identifying an increased risk of major PC in selected patients. PMID- 11192953 TI - Blood gases at rest and during exercise in patients with alpha1-Pi deficiency. AB - Alpha1-protease inhibitor (Pi) deficiency is associated with a protease-anti protease imbalance leading to premature destruction of lung tissue and early emphysema. Little is known about the blood gases of these patients in the various stages of the disease. The purpose of this study was to evaluate blood gases in patients with alpha1-Pi deficiency when patients were at rest and during exercise, and to correlate these with lung function measurements. A total of 369 patients with severe alpha1-Pi deficiency had pulmonary function test and blood gas analysis, 282 also had blood gases taken during steady state submaximal exercise testing. Only 21% of the patients had normal blood gases at rest; 71% had mild hypoxaemia; 8% had severe hypoxaemia. Surprisingly, 61% of the patients with mild lung disease and a FEV1 of more than 65% predicted were hypoxaemic. During exercise 65% of the patients had a drop in PO2 of more than 0.40 kPa. FEV1 was a significant predictor for the PO2 values at rest and during exercise. During exercise the arterial-alveolar gradient increased in about 50% and decreased in 25% of the patients. Many patients with alpha1-Pi have blood gas abnormalities. Impaired blood gases in early stages of the disease result in a discrepancy between lung function parameters and blood gases. FEV1 measurements inadequately capture the extent of lung disease in patients with alpha1-Pi deficiency, and both blood gases at rest and during exercise are needed in the assessment of all stages of the disease. PMID- 11192954 TI - Home-based exercise is capable of preserving hospital-based improvements in severe chronic obstructive pulmonary disease. AB - We examined the feasibility of home-based walking training to maintain the benefits of a short-term exercise training in patients with severe chronic obstructive pulmonary disease (COPD). After initial recovery from an exacerbation, 46 patients were randomized into a training and a control group, and 30 patients completed the programme (mean +/- SD FEV1, 36 +/- 7% predicted). The training group performed a 10-day walking training programme in the hospital, followed by a 6-month programme of supervised walking training at home, integrated into daily activities. The control group did not have exercise training in the hospital or at home. Until 6 months after discharge, lung function, exercise performance and symptom scores were assessed. Six-minute walking distance in the training group improved from day 1 to day 10 (P<0.001) and this effect was maintained over 6 months (P<0.001). On average, daily walking distance at home was 2308 m and walking was reported on 157 days. Quality of life (QoL) scores changed significantly over 6 months (P<0.001). The control group showed no significant changes in exercise performance or QoL scores throughout the whole study period. Therefore, (i) significant improvements in exercise performance and Chronic Respiratory Disease Questionnaire (CRQ) scores could be achieved after recovery from an exacerbation and (ii) these improvements were maintained after discharge, when supported by a home-based walking training. PMID- 11192955 TI - The effectiveness of the visual analogue scale 8 in measuring health-related quality of life for COPD patients. AB - The Visual Analogue Scale 8 (VAS8), consisting of eight linear scales, has been developed to measure health-related quality of life (HRQoL) in chronic obstructive pulmonary disease (COPD) patients. The purpose of this study was to examine the validity and responsiveness of the VAS8. First, HRQoL was assessed in a cross-sectional study with the VAS8 and the St George's Respiratory Questionnaire (SGRQ) in 46 COPD patients. Relationships between the VAS8 and various physiological parameters were examined. Second, in a longitudinal study, changes in HRQoL scores after pulmonary rehabilitation were evaluated in 29 COPD patients. The total VAS8 scores showed a weak correlation with vital capacity and maximal inspiratory pressure and a moderately strong correlation with 6-min walking distance and dyspnoea rating. The total VAS8 score showed a significant correlation with each SGRQ score. Furthermore, almost every VAS8 and SGRQ score improved significantly after pulmonary rehabilitation. The change in the total VAS8 value showed a strong correlation with that of the SGRQ. The VAS8 is well suited to assess HRQoL in COPD patients. Visual analogue scales are generally useful in measuring HRQoL in COPD patients, and the VAS8 is particularly beneficial because of its ease of use. PMID- 11192956 TI - Eosinophil influx into the airways in patients with exercise-induced asthma. AB - Exercise-induced asthma is a common phenomenon, the mechanism of which is undetermined. Eosinophils have been suggested as playing a role in its occurrence. We studied the effect of exercise-induced asthma on the cellular and mediator composition of spontaneously obtained sputum. Twenty-five patients with bronchial asthma were investigated by studying sputum spontaneously obtained before and following challenge. One group with (n=9) and one without (n=9) exercise-induced asthma performed exercise challenge. A third group (n=7) performed methacholine challenge. The sputum was analysed using Giemsa staining for differential cell count, measuring eosinophil cationic proteins and mixtures of leukotrienes (D4, E4 and C4) in the liquid phase using ELISA. The group with exercise-induced asthma had a mean drop of 23.7+/-7.4% in FEV1, significantly (P=0.001) higher than the group without it. Following challenges, there were significant increases in sputum eosinophils only in the group with exercise induced asthma (from 8.1+/-13.9% to 18.3+/-20.2%, P=0.0017) and not in control groups (from 0.9+/-0.9% to 1.5+/-15%) or in those who had methacholine challenge (from 23.6+/-27.2% to 22.3+/-23.8%). Eosinophil cationic proteins did not change significantly in any group. In the liquid phase of the sputum, the amount of leukotrienes increased following exercise in six of the seven patients with exercise-induced asthma in whom it was measured. The influx of eosinophils to the airway in patients who develop exercise-induced asthma can be partially explained by the leukotrienes in the airways of those patients. PMID- 11192957 TI - Efficacy of nebulized fluticasone propionate compared with oral prednisolone in children with an acute exacerbation of asthma. AB - The aim of the present study was to investigate the efficacy and safety of nebulized fluticasone propionate (FP Nebules) compared with oral soluble prednisolone in children with an acute exacerbation of asthma. The study used an international, multi-centre, randomized, double-blind, parallel group design. Three hundred and twenty-one patients, aged 4-16 years old, who presented with an acute exacerbation of asthma, were randomly allocated to either nebulized FP (1 mg b.d.) or oral prednisolone (2 mg kg(-1) day(-1) for 4 days then 1 mg kg(-1) day(-1) for 3 days) for 7 days. Patients in the FP group showed a significantly greater increase in diary card morning peak expiratory flow (PEF) over 7 days compared with patients in the prednisolone group (difference = 9.51 min(-1), CI = 2.1, 16.8, P = 0.034). Similar increases for both treatments were shown for evening PEF. Clinic PEF improved with both treatments, but was significantly greater in patients taking FP after 7 days (difference = 11.41 min(-1), CI = 2.8, 20.0, P = 0.029). Both treatments reduced symptom scores to a similar extent. The two treatments were well tolerated, and there was no difference in the incidence of adverse events. The present study demonstrated that nebulized FP is at least as effective as oral prednisolone in the treatment of children presenting with an acute exacerbation of asthma. PMID- 11192958 TI - Circulating levels of soluble Fas ligand and soluble Fas in patients with chronic obstructive pulmonary disease. AB - Fas- and tumour necrosis factor (TNF) receptor-mediated apoptosis are known to be two principal apoptotic mechanisms in humans. Although there are several distinctions between these two systems, in vitro studies have demonstrated similar hypoxic activation and a functional relationship. Since patients with chronic obstructive pulmonary disease (COPD) show chronic hypoxaemia and the activation of the TNF-alpha system, we investigated whether these pathophysiological changes influence the Fas-Fas ligand system. We measured the circulating soluble Fas ligand (sFas-L) level, an inducer of apoptosis, and the soluble Fas receptor (sFas) level, an inhibitor of apoptosis, in 34 COPD patients and 35 age-matched healthy controls. In addition, we investigated the relationships between the levels of sFas-L or sFas and clinical variables including the TNF-alpha system; circulating TNF-alpha and soluble TNF-receptor (sTNF-Rs: sTNF-R55 and R75) levels, in the COPD patients. Although circulating TNF-alpha, sTNF-R55 and R75 levels were significantly higher in the COPD patients than in the healthy controls, serum level of sFas-L (Fisher's exact probability test; P = 0.26) and plasma level of sFas [COPD patients vs. controls; mean (SD); 3.74 (0.63) vs. 3.67 (0.48) ng/ml; P = 0.89) were not increased in the COPD patients. There was no significant correlation between the levels of sFas-L or sFas and clinical variables in COPD patients. These results suggest that the Fas Fas ligand system does not independently play an important role in the pathophysiology of patients with COPD. PMID- 11192959 TI - Impact of hypoxaemia on neuroendocrine function and catecholamine secretion in chronic obstructive pulmonary disease (COPD). Effects of long-term oxygen treatment. AB - The aim of the study was to investigate the effects of chronic hypoxaemia on neuroendocrine function in hypoxaemic chronic obstructive pulmonary disease (COPD). The stress level was assessed by measurement of daytime plasma catecholamine and nocturnal urinary catecholamine levels and endocrine function was assessed by measuring serum gonadotropins, peripheral sex hormones and peripheral thyroid hormones, and by measuring thyroid stimulating hormone (TSH), prolactin and growth hormone before and after thyroid releasing hormone challenge in 12 male, stable, hypoxaemic COPD patients before and after at least 4 months of long-term oxygen treatment (LTOT). Mean pre-treatment PaO2 was 7.39 +/- 0.78 kPa and mean nocturnal arterial oxygen saturation (MSaO2) was 86.6 +/- 3.2%. Plasma norepinephrine (NE) levels were higher than normal, while all other pre treatment hormone levels were within normal range. Low forced expiratory volume in 1 sec (FEV1) was associated with low basal and stimulated TSH (P < 0.01). Urinary NE excretion correlated positively to nocturnal time spent with SaO2<85% (P<0.05). In similarity with normal controls, positive correlations were found between sex hormone binding globulin and testosterone both before and after LTOT (P<0.01). No significant hormonal changes were noted following an average of 8 months of LTOT for the entire study group. However, in a subgroup (n = 6) with an increase in MSaO2 exceeding 7% points following LTOT, nocturnal excretion of NE and epinephrine were reduced by 30% (P<0.05) and S-free thyroxin by 20% (P<0.05). In conclusion, patients with chronic hypoxaemia secondary to COPD exhibit elevated plasma NE levels but otherwise normal endocrine levels, including a normal hypothalamic-pituitary testicular axis. The severity of airway obstruction is associated with reduced basal and stimulated TSH. The endocrine function is not significantly changed following LTOT except for a subgroup with severe nocturnal hypoxaemia, where elevated nocturnal NE excretion was noted, which was reduced only if whole night oxygenation was normalized during oxygen therapy. PMID- 11192960 TI - Efficacy of salbutamol via Easyhaler unaffected by low inspiratory flow. AB - The fine particle dose delivered via dry powder inhalers (DPIs) is often affected by the inspiratory flow rate generated during inhalation. This has clinical implications, since the fine particle dose determines the amount of drug reaching the lungs. With Easyhaler DPI the fine particle dose remains relatively constant over the range of inspiratory flow rates from 30-60 l min(-1). The aim of this study was to confirm that clinical efficacy is maintained even at low flow rates by comparing the bronchodilating effect of salbutamol (100 microg) delivered via Easyhaler at a target inspiratory flow of 30 l min(-1) with the same dose of salbutamol via pressurised metered-dose inhaler (pMDI) plus spacer. This was a double-blind, randomized, cross-over study with double-dummy technique. Twenty one paediatric and adult asthmatic patients completed the study, which was conducted over 2 study days. The main outcome parameter was forced expiratory volume in 1 sec (FEV1). The patients were trained to generate a low peak inspiratory flow rate (PIFR) of 30 l min(-1), and the actual PIFR through Easyhaler was recorded. The average PIFR through Easyhaler was 28.7 l min(-1). The difference in the maximum value of FEV1 (FEV1max) between the treatments after drug inhalation was 0.01 l. The mean of FEV1max was 2.67 l after pMDI plus spacer compared to 2.69 l after Easyhaler. Improvements in FEV1 were clinically significant. No significant differences between treatments were found. A reasonably low inspiratory flow rate through Easyhaler produces an equivalent improvement in lung function to a correctly used pMDI plus spacer. Hence, Easyhaler can be used with confidence in patients who may have difficulty in generating a high inspiratory flow rate, such as children and the elderly. PMID- 11192961 TI - Early discharge of patients hospitalized with acute asthma: a controlled study. AB - There is no consensus on the optimal length of stay and timing of release from hospital in patients admitted with acute asthma. We hypothesize that it might be safe to discharge patients from hospital once they have responded clinically to intensive anti-asthma treatment. In a non-randomized prospective controlled study, we compared two discharge protocols in consecutive patients admitted for acute severe exacerbations of bronchial asthma. Patients in group A were discharged after remission of signs and symptoms and those in group B after improvement but before complete remission of signs and symptoms. Peak expiratory flow rates (PEFR) were monitored but were not used as discharge criteria for either group. Patients with complicating disease and who were likely to be non compliant were excluded. The length of hospital stay (LOS) and best PEFR at discharge were significantly lower in group B (87 admissions) than group A (80 admissions). The mean (+/-SD) LOS was 1.8(+/- 1) days vs. 3.5(+/- 1.4) days and best PEFR was 58(+/- 17)% predicted versus 71(+/- 15)% predicted respectively (P < 0.001 for both variables). No patient in either group relapsed within 4 weeks of discharge from hospital. We concluded that the release of asthmatics who respond promptly to intensive treatment and are compliant with medication despite incomplete resolution of symptoms, signs and PEFR at the time of discharge from hospital may not be associated with increased risk of early relapse. PMID- 11192962 TI - Pulmonary involvement in Niemann-Pick disease: case report and literature review. AB - Niemann-Pick disease (NPD) is a rare, inherited, autosomal recessive, lipid storage disease. The pathognomonic intracellular accumulation of sphingomyelin results in the production and accumulation of 'foam cells'. Interstitial lung disease is a rare manifestation of NPD. We present the case of a 48-year-old white female with NPD involving the lungs, liver and spleen. The chest radiograph showed bilateral, predominantly basal reticulonodular infiltrates and serial pulmonary function tests over a period of years showed preserved expiratory airflow and a severely decreased diffusion capacity for carbon monoxide (DLCO). In view of her visceral involvement, lack of neurological symptoms and survival into adulthood, we believe our patient represents a case of type B NPD. In this type of NPD, aside from prominent hepatosplenomegaly and sexual immaturity, significant pulmonary infiltration with 'Pick cells' has been reported. To date, no therapeutic modality has been shown to alter the natural history of this disease, which results in progressive debilitation and death. This case is unique in that it provides the longest physiological follow-up in the literature, and provides data on the natural history of pulmonary involvement in NPD. PMID- 11192963 TI - Administering, monitoring and withdrawing oxygen therapy. PMID- 11192965 TI - [Veterinarian emergencies]. PMID- 11192964 TI - [Treatment of ectopic pregnancy with methotrexate]. PMID- 11192966 TI - [Frequency and nature of neurologic emergencies]. AB - In the last decade, it has been shown that neurological problems account for approximately 15% of medical emergencies treated in metropolitan France, in all types of medical establishments. Four major diagnostic groups are concerned: stroke, epilepsy and loss of consciousness, headache, confusional syndromes and behavioural disorders. Among patients seen in emergency units for neurological problems, 80% require hospital admission. These figures underline the need for medical and administrative directors of public hospitals to take greater account of the neurological emergency in providing adequate means to meet this demand. PMID- 11192967 TI - [Confusional state and agitation]. AB - Delirium is a neurologic emergency representative of 10% of the hospitalized patients. It is characterized by an acute and fluctuating change of consciousness and cognition. A strict procedure is necessary to treat quickly the responsible cause among the multiple possible ones. An associated agitation need a quick specific treatment. The treatment should prevent the risk factors, notably iatrogenic, especially in the elderly patients or with previous altered cognitive functions. PMID- 11192968 TI - [Acute headaches]. AB - Etiologic diagnosis of acute headache is made by accurate history of the pain and systematic examination in search of associated signs: the aim of this reasoning procedure is identification of secondary (organic) headache disorders which are infrequent but are needing urgent evaluation and care from primary headaches whose various methods of treatment are specific. PMID- 11192969 TI - [Acute vertigo]. AB - Three questions are raised when a patient experiences sudden vertigo. Is it due to a disease of the vestibule? This would be suggested in case of a revolving nature of the vertigo, the presence of nystagmus and of vestibular ataxia. Are there associated otological (infection of the labyrinth, zoster neuritis) or neurological (ischemic vascular accidents of the cerebral trunk and of the cerebellum, cerebellar haemorrhage) signs? What is the evolution of the sudden vertigo? A single, isolated episode of vertigo will generally be related to vestibular neuritis. However, it may rather be a first episode of repeated vertigo, Meniere's disease, recurrent vertigo, migraine, or very rarely transitory ischemic accident. PMID- 11192970 TI - [Epileptic emergencies]. AB - Convulsive status epilepticus is a major epileptic emergency. Prompt and effective treatment is requested to prevent death or neurological sequel. First line drugs must have a favourable benefit to risk ratio. Refractory status must be treated aggressively by second-line sedative drugs. In this situation, EEG monitoring must diagnose subtle status epilepticus by controlling the disappearance of ictal discharges. Non-convulsive generalized or partial status epilepticus is a diagnostic challenge, best solved by emergency EEG. Immediate discontinuation of antiepileptic drugs is requested to avoid potentially serious idiosyncratic side-effects. Prescriptions habits will be avoided to prevent recurrence of isolated convulsive seizures. PMID- 11192971 TI - [Head injuries in the acute phase]. AB - Half of patients with traumatic head injuries are comatose (Glasgow coma scale < or = 8); motor vehicle accidents among young people are the predominant mode of injury. CT scanner reveals a large variety of lesions such as extracerebral hematomas, focal or diffuse hematomas, deep lesions. Surgery is performed in one quarter of these patients and indications are extracerebral hematomas, depressed fracture or craniofacial wounds. Indications for surgery in focal intracerebral lesions are difficult and depend on patient age, evolutivity and delayed intracranial hypertension; shift on CT scanner and compression of basal cisterns are the predictors of developing intracranial hypertension. Medical treatment depends on patient severity state; with comatose patient, intensive care unit is required with intubation, ventilation and intracranial pressure measurement by ventricular drain. If the pressure is greater than 20 mmHg, barbiturate therapy is indicated. PMID- 11192972 TI - [Cerebrovascular accident]. AB - Stroke is a medical emergency that is common and severe. Its diagnosis is based on questioning of the patient or those around him and on clinical examination. Stroke requires rapid investigation by imagery of the brain and intra- and extracranial vessels. Currently these investigations associate CT scan of the brain (which differentiates infarcts and haemorrhage) and cervical and intracranial ultrasound examination, or angiography if vascular malformation is suspected. Magnetic resonance imaging, when available for emergency use, is greatly superior in its earlier detection of signal abnormalities, its diagnostic precision and visualisation of the vessels. Recent clinical trials have shown the effectiveness of stroke management in specialised units (30% reduction in the number of deaths or institutionalised patients) and of very early intravenous administration of rt-PA (within less than 3 hours). Thus, neurovascular emergency treatment centres should be rapidly established, as has been done in cardiology for emergency care of myocardial infarcts. PMID- 11192973 TI - [Good practice of neuroimaging in neurological emergencies]. AB - CT-scan is the preferred investigation in skull trauma and in any patient with suspected meningeal haemorrhage. Any suspicion of compression of the medulla or of a cauda equina requires emergency investigation by MRI. This investigation is also standard when cerebral thrombophlebitis or meningeal encephalitis is suspected. A future increase in available MRI equipment is desirable in order to enlarge the indications of such imaging, particularly in the case of recent cerebral vascular accident. PMID- 11192974 TI - [Medical studies: new objectives and program of the 2nd cycle]. PMID- 11192975 TI - [Accidental hypothermia]. PMID- 11192976 TI - [Drug-induced skin diseases. Diagnosis]. PMID- 11192977 TI - [Bimalleolar fracture in adults. Mechanism, diagnosis, treatment]. PMID- 11192978 TI - [Macrocytic anemia in adults. Physiopathology, etiology, diagnosis, and treatment]. PMID- 11192979 TI - [Threatened premature labor. Etiology, diagnosis, treatment]. PMID- 11192980 TI - [Clinical trials. Methodologic principles and ethical aspects of treatment evaluation]. PMID- 11192981 TI - [Ear effusion, otalgia. Diagnostic guide]. PMID- 11192982 TI - Placental/umbilical cord blood (PCB) stem cells for transplantation: early clinical outcomes and the status of ex vivo expansion strategies. AB - Placental/umbilical cord blood (PCB) stem cells for transplantation provide a potentially useful alternative for patients who do not have an HLA-matched family or unrelated bone marrow donor. Concerns regarding this source of stem cells include the limited number of stem cells in a PCB unit and the delayed time to platelet engraftment. Because of the limited number of stem cells, there is a very clear cell dose effect for both success of engraftment and time to engraftment. As a result, many transplant centers will only consider PCB stem cells as a second choice for transplanting adults, despite the very favorable profile of post-transplant graft-versus-host disease (GvHD). This has resulted in considerable interest in the development of ex vivo stem cell expansion strategies. This review outlines the current status of PCB transplant outcomes as well as the status of our understanding of stem cell expansion with the currently available technologies. A stem cell dose-limiting effect on outcome will result in a narrower window of clinical indications for the use of this stem cell source, despite the acknowledged reduction in GvHD. The trade-offs between poor engraftment and reduction in fatal or severe chronic GvHD remain to be quantitated. PMID- 11192983 TI - Genetic structure of the five-factor model of personality in a Japanese twin population. AB - Dimensional approaches have been used to describe the fundamental dimensions that underlie the entire domain of normal and pathological personality. We tested the five factor model of personality structure in a sample of Japanese twins, to clarify the contributions of genetic and environment. The revised NEO personality inventory (NEO-PI-R) was administered to 251 twin pairs, ranging in age from 15 to 27 years of age. The NEO-PI-R is a 240-item questionnaire which was developed to assess the dimensions of personality. Univariate genetic analysis showed that the AE model in which phenotypic covariances are explained only by additive genetic (A) and nonshared environment (E) is still a plausible model, and that the relative proportion of genetic influence was comparable to that reported by Loehlin (1992). Multivariate genetic analysis of the Japanese data suggested/revealed that the five factors are genetically dependent on each other and one common genetic factor mediates their interdependence. Previous studies have assumed that they are phenotypically independent and robust. Although there are sampling biases in the present study, it is noteworthy that the results for all five factors depicted by the NEO-PI-R were comparable to those reported by Western researchers, and the genetic structure of the five-factor model is complex. PMID- 11192984 TI - Searching for mechanisms of retinal direction selectivity. AB - A classic example of a complicated neurocomputation carried out by a relatively simple neuronal circuitry is that some mammalian retinal ganglion cells respond selectively to direction of motion. Search for the mechanisms of direction selectivity in the mammalian retina started some 35 years ago. It has been shown that direction selectivity is caused by an asymmetrical inhibition induced by GABA acting on GABAA receptors. However, the physical circuitry underlining this computation is still not clear. A few recent breakthroughs provide important evidence for the sites where the computation takes place. PMID- 11192985 TI - A case of poorly differentiated hilar lung adenocarcinoma of an unidentified histological type. AB - The patient was a 74-year-old man, a physician, whose chief complaint was an unproductive cough. The shadow of a mass was seen at the hilum of the left lung, and the mediastinal lymph nodes on both sides were swollen. No histological diagnosis was obtained even after bronchoscopy, including transbronchial needle aspiration biopsy, but large-cell carcinoma of the lung was diagnosed on the basis of ultrasound-guided biopsy of a shadow in the liver suspected of being a metastatic tumor (T2N3M1, Stage IV). Two courses of chemotherapy (CBCDA + VDS) failed to gain any improvement, and the pain resulting from recurrent bone metastases was managed mainly by the administration of the best supportive care. The patient was readmitted to the hospital after development of numbness in the right upper extremity followed by complication of pneumonia and heart failure, and he passed away. Autopsy revealed a primary hilar lung tumor with a histological diagnosis of poorly differentiated adenocarcinoma. PMID- 11192986 TI - Child and adolescent mental health care. PMID- 11192987 TI - Peptic ulcer disease in the tropics--lessons from India. PMID- 11192988 TI - Seroconversion rate following measles vaccination. AB - OBJECTIVE: To assess the seroconversion rate following measles vaccination in Sri Lankan children. DESIGN: A descriptive study. SETTING: Immunisation clinic, Lady Ridgeway Hospital, Colombo (LRHC). SUBJECTS: 134 infants who attended the LRHC for measles vaccination. MEASUREMENTS: Pre- and post-vaccination blood samples were collected and serum was tested for the presence of anti-measles 1gG antibodies using the ELISA technique. RESULTS: Of the 134 infants only 102 were brought for the post-vaccination sample. Of these 102 samples, 101 were negative for anti-measles antibodies before vaccination. Of the 101 sero-negative samples 94 became sero-positive 6 to 8 weeks after vaccination. These results indicate that the seroconversion rate is 93.06%, which is similar to the results of studies done in other countries. CONCLUSION: Most infants are susceptible to measles infection by the age of 9 months, and it is appropriate to vaccinate infants at this age, as is the practice at present. However, further studies are needed to assess the duration of protection with a single dose of measles vaccine. PMID- 11192989 TI - An attempt to measure burden of disease using disability adjusted life years for Sri Lanka. AB - INTRODUCTION: Disability adjusted life years (DALY) is a measure of burden of disease (BOD) that assesses the years of healthy life lost due to disease or illness. OBJECTIVE: The main objective of the study was to develop a draft measure of the BOD in Sri Lanka, using DALY. METHODS: Computation was done for 100 disease categories identified to reflect the disease pattern in Sri Lanka. Factors that were considered for the calculation of DALY were incidence, degree of disability, duration of the illness and age of onset. RESULTS: Injuries, ischaemic heart disease, asthma, disease of the pulmonary circulation and burns contribute to 55% of BOD in Sri Lanka. CONCLUSION: The highest burden was due to non-communicable diseases, as their duration and degree of disability are high. Diseases such as malaria, which are short term illnesses with low disability, although affecting large numbers, did not give a high value for DALY. PMID- 11192990 TI - The isolation of Burkholderia cepacia in a hospital setting in Sri Lanka. AB - INTRODUCTION: Burkholderia cepacia is widely prevalent in nature. The natural habitat of this organism is soil, water and vegetation, but the hospital environment remains the main source of infection. It causes a wide variety of infections in hospitalised patients. Since there are no reports of its prevalence in Sri Lanka, a data retrieval and analysis was undertaken to determine its incidence among patients at Sri Jayawardenepura General Hospital (SJGH). OBJECTIVE: To determine the prevalence, morphological characteristics, biochemical profile and antibiotic susceptibility pattern of B cepacia in a Sri Lankan tertiary care hospital. METHODS: Relevant clinical data were retrieved from all isolates of B cepacia from SJGH for 12 months from October 1996. Standard procedures were used to isolate the organism from clinical specimens. API 20E was employed for biochemical identification. Antibiotic susceptibility tests was carried out using the modified Kirby Bauer method. RESULTS: B cepacia was isolated from 17 patients. 16 of them were hospitalised and were from the medical, surgical, and intensive care units. All were in a compromised state of health. The organism was isolated from a variety of specimens which included swabs of surgical wounds, chronic ulcers, sputum, bronchial lavage, endotracheal aspirate, urine, peritoneal fluid and blood. Blood agar, MacConkey agar and cystine lactose electrolyte deficient medium supported the growth of all strains. They were motile Gram negative rods. All strains were oxidase positive. Strains gave variable results with other biochemical tests. Antibiograms too were variable. All strains were sensitive to ceftazidime, and the majority of the strains were sensitive to the other third generation cephalosporines. All strains were resistant to four or more antimicrobial agents included in the study. Of the 17 patients from whom B cepacia was isolated, only 9 seem to have had actual infection; others were probably instances of colonisation or contamination. CONCLUSIONS: The present report confirms the prevalence and importance of B cepacia as a hospital pathogen in Sri Lanka. Hospital laboratories should be equipped to isolate, identify and perform antibiotic sensitivity test on these strains. Antibiotic susceptibility testing is necessary as the patterns seem to differ among strains. The multiple drug resistant nature of the organism warrants strict infection control measures to prevent spread in a hospital setting. PMID- 11192991 TI - Gender differences in undergraduate medical examination results in Sri Lanka. AB - OBJECTIVE: To identify possible gender related differences in performance at undergraduate medical examinations in Sri Lanka. STUDY DESIGN AND METHODS: Results of examinations conducted by the faculty of medicine, University of Kelaniya in 1997 and 1998, and data published by the University Grants Commission (UGC) on final examinations conducted by 4 other Sri Lankan medical faculties (in the Universities of Colombo, Peradeniya, Ruhuna and Jaffna) in 1996 and 1997, were analysed for sex related differences. RESULTS: The proportion of women in each batch of students who sat for 8 examinations conducted at the faculty of medicine, University of Kelaniya in 1997 and 1998, ranged from 40.7 to 48.4% (average 44.3%). Among students sitting for the final MBBS examinations in other medical faculties in 1996 and 1997, the proportion of women ranged from 37.3% in Peradeniya to 53.7% in Jaffna. The proportions of women who obtained "classes" were higher than that of men in 12/15 examinations, with statistically significant differences in four. Higher proportions of men were referred or failed in all 8 examinations analysed; the differences were statistically significant in two. CONCLUSIONS: Women appear to do marginally better than men in undergraduate medical examinations in Sri Lanka. PMID- 11192992 TI - Prevalence of skin diseases in suburban Sri Lanka. AB - BACKGROUND: In Sri Lanka the only available measures of disease frequency related to skin disorders are from hospital-based clinic studies. They reflect only the patterns of clinic attendance, and the actual prevalence of skin diseases in the community is unknown. The main objective of this study was to determine the prevalence of skin diseases in a selected area. METHODS: A household survey based on health interviews and clinical examination was conducted over a period of 4 months. 418 households were selected for modified cluster sampling from predetermined areas in Piliyandala. RESULTS: There were 1806 people residing in the 418 households surveyed. 894 cases were identified, of which 34 people could not be traced for clinical examination. 33 households did not have anyone with a skin lesion. The prevalence of skin disease was 47.6%. Fungal infections, followed by dermatitis, were found to be the commonest problems. There was only one case of leprosy. Psoriasis was found to be of low prevalence. CONCLUSIONS: The overall prevalence of skin disease was high in the community that we surveyed. There were marked differences between community prevalence and hospital dermatology clinic attendance data for a number of skin diseases. PMID- 11192993 TI - Male and female filarial worms Dirofilaria (Nochtiella) repens recovered from the scrotum. PMID- 11192994 TI - A perforated duodenal ulcer in a child. PMID- 11192995 TI - Urinary tract infection in children; collection and transport of urine, and colony counts. PMID- 11192996 TI - Neonatal purpura fulminans due to protein C deficiency. PMID- 11192997 TI - Salmonella typhi and chloramphenicol resistance. PMID- 11192998 TI - Primary writing tremor. PMID- 11193000 TI - Some problems at the General Hospital, Jaffna. PMID- 11192999 TI - Interfollicular Hodgkin's disease with histological features of Castleman's disease. PMID- 11193001 TI - Neurotransmitters adenosine triphosphate and noradrenaline induce nitric oxide release in rat vas deferens. AB - 1. In rat vas deferens, electrical field stimulation (EFS) evoked a muscular biphasic tetrodotoxin (TTX)-sensitive contractile response. 2. The amplitude of this response increased with the frequency of stimulation. 3. After each stimulation, nitric oxide (NO) release was assayed and found to be released in a frequency-dependent manner. 4. NO release also occurred after treatment with exogenous neurotransmitters, adenosine 5'-triphosphate (ATP) and noradrenaline (NA). 5. Prazosin and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), respective antagonists of alpha1-adrenoceptors and P2x purinoceptors, inhibited NO release induced by NA and ATP. Both prazosin and PPADS inhibited NO release by EFS. 6. TTX failed to modify the NO release induced by exogenous neurotransmitters but abolished the release of NO and contractile response by EFS. 7. EFS and released noradrenaline and ATP induce the release of NO through postjunctional alpha1 -adrenoceptors and P2x-purinoceptors, respectively. PMID- 11193002 TI - The alpha-adrenoceptor antagonist, zolertine, inhibits alpha1D- and alpha1A adrenoceptor-mediated vasoconstriction in vitro. AB - 1. The antagonist effect of zolertine (4-phenyl-1-[2-(5 tetrazolyl)ethyl]piperazine trihydrochloride), on vascular contraction elicited by noradrenaline in aorta, carotid (alpha1D-adrenoceptors), mesenteric (alpha1A/D adrenoceptors) and caudal arteries (alpha1A-adrenoceptors) from Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats and rabbit aorta (alpha1B adrenoceptors), was investigated in endothelium-denuded arterial rings. 2. The selective alpha1D-adrenoceptor agonist, noradrenaline, elicited concentration dependent contractions in all arterial rings from both species. Noradrenaline selectivity was: carotid = aorta >> mesenteric = rabbit aorta > caudal arteries. 3. The contractile responses induced by noradrenaline were competitively antagonized by zolertine in rat carotid and aorta arteries, yielding pA2 values of WKY, 7.48 +/- 0.18; SHR, 7.43 +/- 0.13 and WKY, 7.57 +/- 0.24; SHR, 7.40 +/- 0.08, respectively. Zolertine was a non-competitive antagonist in some blood vessels as Schild plot slopes were lower than unity. The pKb estimates for zolertine were WKY, 6.98 +/- 0.16; SHR, 6.81 +/- 0.18 in the mesenteric artery, WKY, 5.73 +/- 0.11; SHR, 5.87 +/- 0.25 in the caudal artery and 6.65 +/- 0.09 in rabbit aorta. 4. Competition binding experiments using the alpha1-adrenoceptor antagonist [3H]prazosin showed a zolertine pKi of 6.81 +/- 0.02 in rat liver (alpha1B-adrenoceptors) and 6.35 +/- 0.04 in rabbit liver (alpha1A-adrenoceptors) membranes. 5. Zolertine showed higher affinity for alpha1D-adrenoceptors compared to alpha1A-adrenoceptors, while it had an intermediate affinity for alpha1B adrenoceptors. The ability of the alpha1-adrenoceptor antagonist zolertine to block alpha1D-adrenoceptor-mediated constriction in different vessels of WKY and SHR rats may explain its antihypertensive efficacy despite its low order of potency. PMID- 11193003 TI - Functional antagonism between nitric oxide and ATP in the motor responses of guinea-pig ileum. AB - 1. The interaction of nitric oxide and ATP in the non-adrenergic, non-cholinergic (NANC) motor responses and the presence of NADPH-diaphorase and quinacrine positive myenteric neurones were studied on guinea-pig ileum using mechanographic, histochemical and quinacrine-fluorescence techniques. In the presence of phentolamine, propranolol and atropine, the non-precontracted longitudinally oriented organ bath preparations responded to sodium nitroprusside (1-100 microM) or ATP (5-50 microM) with tetrodotoxin (0.1 microM)-resistant relaxation or contraction, respectively. The effects of ATP were suramin (50 microM)- and apamin (5 microM)-sensitive. 2. The NANC motor responses elicited by electrical stimulation (0.8 ms, 1-20 Hz, 20 s) consisted of tetrodotoxin sensitive relaxation phase followed by a phase of twitch-like and tonic contractions. 3. NG-nitro-L-arginine (L-NNA, 0.1-0.5 mM) inhibited or abolished the relaxation phase. L-arginine (0.5 mM), but not D-arginine (0.5 mM), restored the relaxation phase in L-NNA-pretreated preparations. The relaxation phase increased after ATP-induced desensitization of purinoceptors and in the presence of suramin (50 mciroM) but was abolished by apamin (5 microM). 4. The phase of contractions was enhanced by L-NNA (0.1-0.5 mM) and restored by L-arginine (0.5 mM). The twitch-like and tonic contractions were decreased during ATP-induced purinoceptor desensitization and in the presence of suramin (50 microLM). Apamin (5 microM) inhibited the tonic contractions. 5. The desensitization of purinoceptors by ATP did not change the L-NNA-induced inhibition of the relaxation phase but decreased the L-NNA-increased phase of contractions. L-NNA reduced the relaxation phase and increased the phase of contractions during purinoceptor desensitization. 6. We conclude that in the longitudinal muscle layer of the guinea-pig ileum, nitric oxide mediates the relaxation phase while ATP contributes via smooth muscle P2 purinoceptors to the phase of contractions suggesting a postjunctional functional antagonism between nitric oxide and ATP. The presence of NADPH-diaphorase- and quinacrine-positive neuronal cells and processes running to the muscle cells confirms a physiological role of nitric oxide and ATP in the ileal neurotransmission. PMID- 11193004 TI - Effects of natural tachykinins on porcine lower urinary tract smooth muscle. AB - 1. The aim of our study was to ascertain the possible differences and/or similarities in natural tachykinin activity in vitro on lower urinary tract of large-sized animals as compared with data obtained in laboratory animals. 2. Besides tachykinins normally present in mammals, namely substance P (SP), neurokinin A (NKA) and neurokinin B (NKB), we tested non-mammalian tachykinins, such as eledoisin (ELED), physalaemin (PHYS), kassinin (KASS) and PG-kassinin II (PG-KASS II). 3. NKA, KASS and ELED were found to be the most potent peptides in contracting detrusor strips from porcine bladder. In particular, NKA showed a pD2 of 7.14, whereas KASS and ELED showed pD2 values of 7.20 and 7.22, respectively. The activity of NKB and PG-KASS II corresponded to 72.4 and 55.0% respectively of that of NKA. SP and PHYS activity corresponded to only 2% of that of NKA. 4. NKA (pD2 7.92) was the most active peptide in contracting bladder neck tissues as well. ELED and KASS were found to have lower, similar pD2 values (7.62 and 7.70, respectively), whereas NKB and PG-KASS II were much less active (pD2 7.12 and 6.74, respectively). Moreover, SP and PHYS showed an activity range lower than 2% of that of NKA. 5. The reported results confirm that, on pig vesical neck and detrusor, NK1 receptors represent a minority as compared with NK2 and NK3 receptors. By contrast, the presence of NK2 receptors is demonstrated by a greater potency of NKA. The presence of NK3 receptors both on detrusor and neck is evidenced by NKB activity and by results achieved with PG-KASS II. PMID- 11193005 TI - Effects of eicosanoids and nitric oxide on the noradrenaline-induced contractions in the rat mesenteric bed. AB - 1. The effects of the inhibition of the metabolism of arachidonic acid (AA) on the constrictor responses to noradrenaline (NA) were studied in the rat perfused mesenteric bed. The inhibitor of all the pathways of AA metabolism, 10 microM eicosatetraynoic acid (ETYA), reduced the constrictor responses to all the concentrations of NA assayed. 2. The constrictor responses to NA were also reduced by the cyclooxygenase (COX) inhibitor, indomethacin (10 microM), as well as by the lipoxygenase inhibitor, nordihidroguaiaretic acid (1 microM; NDGA), whereas they were unmodified by the cytochrome P450 monooxigenase inhibitors, clotrimazole (10 microM), metyrapone (10 microM) and proadifen (10 microM). 3. The reduction in NA contractility induced by indomethacin was reverted with a decreasing order of potency by the thromboxane A2 analogue, U-46619 > prostaglandin (PG) E2 > PGF2alpha. The exposure of the mesenteric bed to NA increased the production of PGF2alpha, whereas it did not modify the production of the remaining AA metabolites. 4. The increase in the NA-induced contractions caused by endothelium removal, as well as by the inhibition of nitric oxide synthase (NOs) with NG-nitro-L-arginine methyl ester (400 microM; L-NAME), was suppressed by indomethacin but not by NDGA. These observations suggest that the lipoxygenase-derived metabolites are formed in the endothelium, whereas the COX derived metabolites are formed in the vascular smooth muscle. 5. The TP receptor antagonist, SQ29548, did not modify the NA-induced contractions, either in the presence or in the absence of the endothelium. 6. Contractions elicited by KCI (60-100 mM) were unmodified by the AA metabolism inhibitors, ETYA, NDGA and indomethacin. 7. In summary, these results show that metabolites of AA, through both the COX and the lipoxygenase pathways, are involved in the NA-induced contractions in the rat mesenteric bed. The lipoxygenase metabolites are likely to be formed in the vascular endothelium, whereas the COX metabolite, which could be PGF2alpha, is apparently formed within the vascular smooth muscle. PMID- 11193006 TI - M3 muscarinic receptors but not M2 mediate contraction of the porcine detrusor muscle in vitro. AB - 1. The objective of the study was to determine the role of muscarinic receptor subtypes in mediating contraction of the porcine detrusor smooth muscle in vitro. 2. Strips of pig detrusor muscle were set up in physiological salt solution and the tensions developed by the tissues were recorded. Responses to carbachol were obtained in the absence and presence of a range of muscarinic antagonists (4 DAMP, methoctramine, darifenacin, oxybutynin, tolterodine and pirenzepine). Antagonist affinity values (pKB values) were calculated and compared with those quoted in the literature for these antagonists at each of the muscarinic receptor subtypes. 3. The M3-selective antagonists, 4-DAMP and darifenacin had high affinities (pKB values of 9.4 and 8.6, respectively). Oxybutynin, tolterodine and pirenzepine had affinities of 8.2, 8.1 and 6.8, respectively, whilst the M2 selective agent methoctramine had a relatively low affinity (pKB = 6.1). The rank order of affinities was, therefore, 4-DAMP > darifenacin > oxybutynin > tolterodine > pirenzepine > methoctramine for the pig detrusor. Correlation of the antagonist affinities obtained on the bladder with those published for these antagonists at the five muscarinic receptor subtypes identified the M3(m3) receptor as the muscarinic subtype mediating detrusor contractile responses in vitro. 4. These data suggest that a small population of M3-muscarinic receptors must mediate direct contractile responses of the pig detrusor muscle to muscarinic receptor stimulation in vitro. PMID- 11193008 TI - Effects of clofilium on cardiovascular tissues from normo- and hypertensive rats. AB - 1. The overall aim was to test whether clofilium has some potential as a positive inotrope for heart failure. We used Wistar Kyoto normotensive rats (WKY) and spontaneously hypertensive rats (SHRs) and studied the effects of clofilium on isolated blood vessels, left ventricular action potentials and left ventricular contractility. 2. Clofilium at < or = 10(-6) M had no effect on WKY portal vein contractions and at < or = 3 x 10(-4) M had no effect on WKY or SHR quiescent mesenteric and intralobar pulmonary arteries. 3. Clofilium at 10(7) - 10(-5) M prolonged the WKY left ventricular action potentials and with 10(-6) and 10(-5)M this included after-depolarizations. 4. Clofilium at < or = 3 x 10(-5) M augmented the peak force, prolonged the contractions and did not cause arrhythmias in the absence and presence of isoprenaline on left ventricle strips from 12-month-old WKY. 5. The 12-month-old SHR has hypertrophy of the left ventricle with reduced peak force and prolongation of relaxation. The effects of clofilium on 12-month-old SHR left ventricle contractility were similar to those in the age-matched WKY. 6 In summary, clofilium has positive inotropic effects on the rat left ventricle that are maintained in hypertrophy. Clofilium does not have effects on blood vessels that would be detrimental in heart failure. Clofilium prolongs the rat left ventricle action potential and causes after depolarizations. The pro-arrhythmic potential of clofilium, however, makes it unlikely that it could be used as a positive inotrope in the treatment of heart failure. PMID- 11193007 TI - Functional innervation of the biliary sphincter of the guinea-pig revealed by anti-autonomic drugs. AB - 1. The roles of excitatory and inhibitory intrinsic motor nerves on contractions reflexly evoked by wall distension were investigated in the isolated sphincter of Oddi of the guinea-pig (SO-GP). 2. Distension of the terminal bile duct for 30-60 s time periods increased the frequency of contractions from about 2 to 12 min(-1) (n = 16). 3. Hexamethonium (HEX; 300 microM) largely prevented the distension evoked increase in contraction frequency (4.5 min(-1), n = 8) as did atropine (ATR; 1 microM) (0.8 min(-1), n = 6), while tetrodotoxin (TTX; 1 microM) blocked the contractions triggered during distension. 4. L-nitroarginine (L-NA; 100 microM) significantly increased the frequency of contractions during and in the absence distension while apamin (APAM; 0.5 microM) significantly increased their frequency and doubled their mean amplitude during distension. 5. These results suggest that distension activates excitatory cholinergic motor nerves to increase the frequency of contractions in the SO-GP. These actions are modulated by the concomitant activation of intrinsic nitrergic and non-nitrergic inhibitory motor nerves. PMID- 11193009 TI - Hearing where we're coming from--ethically and professionally. AB - Anthropologists concerned about the discipline's ability to cope ethically and ethnographically with a globalized world should not dismiss too hastily the methodology--and the ethics built into it--that anthropology developed over the last century. This methodology of making "displacing" translations, based on ethnographic experience and a politics of translation, can still provide a workable ethics and a viable labor of ethnography even in the world at present. PMID- 11193010 TI - Negotiating ethical and legal mazes in the federal workplace. AB - The mandates that control actions in the federal workplace often challenge academic principles of conduct. Particularly vulnerable is the anthropologists' image of themselves as champions of powerless and voiceless groups in an arena perceived as dominated by a hostile government. This is coupled with convictions that socially responsible anthropology respects individual privacy while disseminating data to encourage culturally informed public and federal decisions. Using examples involving federal cultural and natural resources, we show conflicts within this suite of perspectives and with the demands of the federal workplace. The need for legally defensible decisions, responses to publics with diverse agendas, and requirements for confidentiality and public access to government records test our anthropological convictions as well as available legal protections of individual privacy and the public's right to know. Perhaps the anthropological community will strategize about more effective remedies for the problems of meeting the concerns of the individuals and the publics it cares about. PMID- 11193011 TI - The practice and politics of archaeology in Egypt. AB - Archaeologists working in Egypt have rarely considered the local/global ramifications and responsibilities of their field practices: many continue to operate under what might be termed the residual effects of colonialism. Taking an explicitly postcolonial stance I argue that there is much more at stake than the intellectual enterprise. This paper outlines the ways in which scholars could undertake a more engaged archaeology and how we might more closely be involved with the people and pasts of modern Egypt. The connected tensions of tourism and terrorism are foregrounded, demonstrating that heritage issues are salient to both spheres. Finally, I explore the nation's relationship to its pharaonic past over the past few centuries and include some contemporary articulations and representations. PMID- 11193012 TI - Ethical issues in the ethnography of cyberspace. AB - The project of developing an anticipatory anthropology of the future reveals unique ethical opportunities. For example, the increased importance of performance means there is a substantial potential for a substantive "resocialing" of work in organizations, just as the decline of Modernism opens space for collective, situated ethics as opposed to individualized categorical imperatives. An anthropology of the future should address the question of the future of ethics in general. The very possibility of human agency, of informed individual moral action, is brought into question in new ways. The profound flexibility of the computer as a medium carries with it the dangers of hyper abstraction, while the consolidation of capital reproduction on a global level increases the scope for apparently permanent mystification. Also important are the new ethical challenges raised for those engaged in knowledge "production" or science broadly conceived. These include the necessary effort to acknowledge fully the role of non-human agency, and the potentially profound possibilities in a transformation in the character of knowledge, a correlate, at least in part, of the commodification of knowledge associated with distance learning. These challenges accompany the more overt threats of transgenic entities and ecological degradation. How can one be an ethical intellectual or academic under these circumstances, let alone teach others to be? There are also some specific challenges facing anthropology in particular. Some derive from the increasing "privatization" of ethnography, both in its growing popularity in modes of social reproduction more directly implicated in the reproduction of capital and in the declining academic support for anthropology. In a very specific sense, anthropology has grounded its ethics on an appreciation of and support for the reproduction of "really existing" culture. This ethical compass is not available to the ethnographer who studies the future. How do we participate ethically in the construction of a future in whose character we are inevitably implicated? PMID- 11193013 TI - Working toward an ethical anthropology. Where do we go from here? AB - This article posits an ethical anthropology for the 21st century that addresses and informs our understanding of international conflict situations and their solutions while providing methodologies for anthropologists of color to position their issues of concern at the center of social science discourse. PMID- 11193014 TI - Ethics in anthropology: dilemmas and conundrums. AB - This paper is a call for awareness and continual examination of the multifaceted nature of ethics and closely related ideas as they relate to anthropology. At the very least, the lack of common understanding of these ideas has been and continues to be a pressing prblem for all who practice anthropology. In this vein, abbreviated etymologies of these critical concepts are put forth as prologue to forays into ethics in the academy and of science as context for ethical maneuver. Shifting conditions in anthropology are then described in relation to altered ethical orders with examples of early hints of the contemporary scene being drawn from Oscar Lewis's commentary on the raucous reception in Mexico of his book The Children of Sanchez. PMID- 11193015 TI - Ethical dilemmas. What's new, what's not. AB - The ethical issues and conflicts facing anthropology have precedents in the past because they are intrinsic to anthropological practice. What is different about them now is that they are played out in new sites, with added complexities, and without changed relations of anthropologists to those with stakes in their research, especially "the people" they study. A review of the unintended consequences of the American Anthropological Association's efforts to define a code of ethics in the 1960s offers lessons that are applicable today. PMID- 11193016 TI - Towards a public health approach to bioethics. AB - In this paper we examine the central commitments of bioethical enquiry and reasoning from a public health perspective. We argue that a core element of American national culture is individualism, which resonates in scholarly and popular debates. Our contention is that the habitus of bioethical debate is in large measure animated by an overriding concern with the individual, and the resulting social practice of the community has been to downplay the importance and legitimacy of group-level health care dilemmas. This paper calls for re focusing of bioethics by employing a public health perspective, which would include a population focus, evidence-based research topics, and engagement of the ethical dilemmas that arise from decisions concerning prevention. Racial and ethnic health disparities throughout the life span of a population in central New York State are used to illustrate the need for a public health focus in bioethics. PMID- 11193017 TI - Globalization of research and international standards of ethics in anthropology. AB - Ethics and anthropology have entered the era of globalization, and professional discourse about ethics can no longer be confined to a national or domestic dialogue. Anthropology must vigorously join the international dialogue and debate over globalization and the conduct of research across cultures; indeed it is the discipline most suited to command the high ground in this discourse. American anthropology historically has been more reactive than proactive in ethics, but cannot remain so as the nature and condition of research have fundamentally changed in a postcolonial world. Indigenous peoples, Third World researchers, international development workers in government and non-government agencies, and other anthropologists outside of the U.S. are raising questions about international research that are generating new standards of conduct. Anthropology as a discipline and a profession must keep apace with these developments or it will lose ground in a crucial arena of global discourse. PMID- 11193018 TI - Facing racism and the moral responsibility of human rights knowledge. AB - Anthropologists working in arenas of human rights advocacy must be prepared to negotiate dilemmas of human responsibility. Those focusing on racial discrimination as a breach of international human rights conventions must contend with trends in social research that feed into politically consequential claims that neither race nor racism exist as significant social facts. An examination of the global sociocultural and geopolitcal landscape, the human rights system, and models of change reveals that contemporary racism in both its marked and unmarked varieties warrants anthropologists' critical scrutiny and, depending on individual epistemological and political inclination, sociopolitical intervention. PMID- 11193019 TI - If anthropology is global, then so are its ethical dilemmas. AB - This paper reviews three personal situations of the author as a student: an NGO activist in the women's movement and a UN official working on women's health and tobacco. Each situation, the kinds of ethical issue posed and lessons for the future direction of ethics in anthropology are outlined. The paper argues that applied anthropology is embedded in the position of the field of anthropology within the politics of the State and that this defines the parameters of individual choice. Contradictions in ethical situations and decision-making are posed by changing from the distant observer to active involvement and these may not be resolved by logic alone. Furthermore, governance and defining global ethical standards such as for the behavior of the tobacco multinational corporations is a fascinating new realm for anthropological ethical resolve. PMID- 11193020 TI - "Who knows the power of his bones". Reburial redux. AB - This paper discusses the repatriation of human remains to indigenous peoples in Australia and the United States and the role anthropologists play in the construction of past, present, and future identities for contemporary indigenous peoples. Using examples from both countries, I suggest that many of the participants at the reburials, and in the events leading up to them, were not only reburying their dead ancestors and addressing religious concerns, but were also redeeming past social injustices, renegotiating the status quo, and affirming their modern social and religious identity--all important issues for Fourth World peoples living in First World nation-states today. Reburials are powerful social dramas, testimony to the complex historical relationships between and among all concerned, living and dead, indigenous and non-indigenous. I also argue that as Fourth World peoples attempt to renegotiate the status quo by turning to the past and reburying their ancestors, the important role of anthropologists in this effort should be considered in terms of both practice and theory. Because of the combination of heritage/cultural resource management legislation, government regulations, a changing professional ethic in regards to issues of repatriation, anthropologists in all subdisciplines are increasingly involved in the witting and unwitting reproduction of indigenous social orders. The implications of this and its ethical dilemmas for anthropologists working in all the subdisciplines and in varied workplaces are explored. The necessity of working with indigenous communities is underscored and suggestions for working toward a common universal heritage are presented. PMID- 11193021 TI - Molecular anthropology and race. AB - Molecular analyses have led to many recent advances in the study of human variation. The addition of DNA analyses of fossils now allows the testing of hypotheses derived from sampling living people. Further sampling of all of the regions of the human genome has led to a remarkably consistent evolutionary scenario that helps to explain the patterns of variation found today. PMID- 11193022 TI - Ethics and anthropology: Facing future issues in human biology, globalism, and cultural property. Proceedings of a meeting. April 14, 2000. New York, New York, USA. PMID- 11193023 TI - Programmed cell death (PCD). Apoptosis, autophagic PCD, or others? AB - The occurrence of cell death as a physiological event in multicellular organisms has been known for more than 150 years; in 1972 the term apoptosis was introduced on morphological grounds. However, accumulating evidence suggests that programmed cell death (PCD) is not confined to apoptosis, but that cells use different pathways for active self-destruction as reflected by different morphology: condensation prominent, type I or apoptosis; autophagy prominent, type II; etc. Autophagic PCD appears to be a phylogenetically old phenomenon; it may occur in physiological and disease states. We have studied the relation between morphological and biochemical events during autophagic and apoptotic PCD in human mammary, lymphoblast, and colon cancer cells using electron microscopy and proteom analysis. We find that autophagic cell death (type II) PCD includes degradation of Golgi apparatus, polyribosomes, and endoplasmic reticulum, which precedes nuclear destruction. Intermediate and microfilaments are largely preserved; presumably the cytoskeleton is required for autophagocytosis. Apoptosis (type I) PCD is characterized by condensation of cytoplasm and preservation of organelles; cytoskeletal elements disintegrate in early stages. Either type of PCD involves synthesis of distinct proteins. Finally, both types of PCD share features some of a cell's stress response (e.g., translocation of hsp90). In conclusion our findings support the concept that autophagic cell death is a separate pathway of PCD distinctly different from "classical" apoptosis. However, autophagic and apoptotic PCD should not be considered as mutually exclusive phenomena. Rather, they appear to reflect a high degree of flexibility in a cell's response to changes of environmental conditions, both physiological or pathological. PMID- 11193024 TI - Mechanisms of cell death II. Proceedings of the 3rd Annual Conference of the International Cell Death Society. May 6-10, 2000. Escorial, Spain. PMID- 11193025 TI - First and second messenger role of calcium. Survival versus apoptosis in serum free cultured granulosa explants. AB - In order to elucidate the causal relationship between increased intracellular free calcium ([Ca2+]i) and induction of apoptosis, serum-free cultured granulosa cell (GC) explants were subjected to various experimental protocols interfering with normal Ca2+ homeostasis. Modulation of apoptotic indices was calculated on DAPI-stained GC explants. In some experiments [Ca2+]i was measured with the Ca2+ probe fura-2 in combination with epifluorescence microscopy. Buffering of [Ca2+]i with BAPTA-AM resulted in inhibition of apoptosis, while increasing extracellular Ca2+ (otherwise called [Ca2+]e load) resulted in a biphasic response characterized by an initial inhibitory effect on apoptosis followed by a delayed phase of increased apoptosis that became apparent at 4 h after withdrawal of the [Ca2+]e load. The initial inhibitory effect of the [Ca2+]e load on apoptosis was dependent on the concentration of the load (range 2-50 mM), was augmented when the [Ca2+]e load was applied in the presence of the Ca2+ channel blocker methoxyverapamil, and was mimicked by applying Mg2+ and Gd3+, two Ca(2+)-receptor agonists. These observations point towards the involvement of an extracellular Ca(2+)-sensing receptor (CaR). Measurements of [Ca2+]i showed that the ion was increased just after [Ca2+]e load, followed by recovery that was complete at 2 h after the load. Collectively these data suggest that a [Ca2+]e load initiates apoptosis, becoming manifest 4 h later, by the provoked [Ca2+]i increase, and this effect is preceded by an apoptosis-inhibiting phase presumably involving CaR activation. We conclude that Ca2+ may act as a first (extracellular) messenger promoting cell survival and as a second (intracellular) messenger activating the cell death pathway. PMID- 11193026 TI - Primary human fibroblasts from a maple syrup urine disease patient undergo apoptosis following exposure to physiological concentrations of branched chain amino acids. AB - Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by a deficiency in branched chain alpha-ketoacid dehydrogenase. We have recently found that MSUD neurodegeneration may result, at least in part, from apoptosis triggered by branched chain amino acids and their alpha-ketoacid derivatives. In the present study, we investigated the sensitivity of MSUD fibroblasts to defined mixtures of MSUD metabolites. Defined combinations of MSUD metabolites, at levels comparable to those in MSUD patients, triggered cell death in skin fibroblasts from a MSUD patient, while control fibroblasts were resistant. The mechanism of cell death was confirmed as apoptosis by in situ end labeling. PMID- 11193027 TI - Heat shock protein 70 is required for the survival of cancer cells. AB - The major stress-inducible heat shock protein, Hsp70, is a chaperone protein abundantly and preferentially expressed in human tumors and tumor cell lines. Owing to the ability of Hsp70 to protect cells from a wide range of apoptotic and necrotic stimuli, it has been assumed that Hsp70 may confer survival advantage to tumor cells. To investigate this hypothesis in human tumor cell lines, we generated an adenovirus expressing antisense Hsp70 (Ad.asHsp70). The effective and specific depletion of Hsp70 by Ad.asHsp70 resulted in massive cell death of all tumorigenic cell lines tested (carcinomas of breast, colon, prostate and liver as well as glioblastoma). In spite of an effective depletion of Hsp70, Ad.asHsp70 had no effect on the survival or growth of fetal fibroblasts or non tumorigenic epithelial cells of breast or prostate. Anti-apoptotic proteins Bcl 2, Bcl-XL and CrmA as well as peptide-inhibitors of caspases, DEVD-CHO and zVAD FMK, failed to rescue tumor cells from Ad.asHsp70-induced cell death. These results indicate that the high expression of Hsp70 is a prerequisite for the survival of human cancer cells of various origins and reveal Hsp70 as the only protein described so far whose expression is specifically needed for the survival of tumorigenic cells. PMID- 11193028 TI - The interaction of HSP27 with Daxx identifies a potential regulatory role of HSP27 in Fas-induced apoptosis. AB - The heat shock protein HSP27 protects cells against a wide variety of toxic treatments and blocks apoptosis induced by exposures to anticancer drugs and activation of the death receptor Fas. The molecular mechanisms of protection are unknown but appear to be regulated by phosphorylation of HSP27. Two apoptotic pathways can be activated downstream of Fas. The Fas-adaptor FADD mediates a caspase-dependent pathway. Fas also activates a caspase-independent pathway which correlates with Fas-induced translocation of Daxx from the nucleus to the cytoplasm and involves the interaction of Daxx with Fas and Ask1. We found that phosphorylated dimers of HSP27 interact with Daxx, preventing its interaction with Ask1 and Fas and blocking Daxx-mediated apoptosis. Expression of HSP27 also prevents the translocation of Daxx from the nucleus to the cytoplasm which is induced upon expression of Ask1 or stimulation of Fas. The observations reveal a new level of regulation of the Fas pathway. Whereas the FADD axis can be modulated by expression of FLIP, a natural inhibitor of FADD, our results show that HSP27 can accomplish a similar function for the Daxx axis. PMID- 11193029 TI - Apoptosis as a scaffold for building up the B cell repertoire. AB - Control of cell number is determined by a balance between cell proliferation and cell death, both of which are highly regulated processes, with numerous checks and balances. Cells control their own death through activation of an internally coded suicide program that, when activated, initiates a characteristic form of cell death called apoptosis. This type of regulation allows elimination of cells that have been produced in excess, that have developed improperly, or that have sustained genetic damage. Apoptosis is, therefore, the most common physiological form of cell death and occurs during embryonic development, tissue remodeling, immune regulation, cell activation and tumor regression. PMID- 11193030 TI - A single cell analysis of apoptosis. Ordering the apoptotic phenotype. AB - Microcinematography was applied to the analysis of the kinetics of apoptotic cell death. Apoptosis was found to be a process that proceeds in different cells at different times after an initial stress, and therefore kinetic studies of apoptotic events in bulk cultures can be problematic. Using single cell analysis we found that stronger apoptotic stimuli induce an earlier onset of apoptosis, but that there is no relationship between time of onset and duration of the apoptotic process. That is, cells that initiate apoptosis shortly after induction do not proceed more rapidly through the process. This suggests an all-or-non mechanism that is supported by some models of the biochemical pathways of apoptosis. PMID- 11193031 TI - Molecular mapping of the physiological cell death process. Mitochondrial events may be disordered. AB - The mitochondrion plays a central role in Bcl-2-inhibitable physiological cell deaths. The detailed order of mitochondrial and other events during cell death in vivo remains ambiguous, however. As part of an effort to explore this issue, we have asked whether mitochondrial dissolution during physiological cell death occurs in an orderly and concerted process. Here, we describe the characterization of two elements of mitochondrial disintegration on the level of individual cells. Using a novel cytofluorimetric approach, we have assessed simultaneously the release of cytochrome c (specifically a fluorescently tagged transfected construct) from mitochondria and the dissipation of mitochondrial membrane potential. Our results indicate that mitochondrial disintegration does not follow a strictly ordered process and is not concerted. We are extending these studies to further characterize mitochondrial events in the context of Bcl 2 family members and place them definitively within the context of the caspase cascade. PMID- 11193032 TI - Mitochondrial control of cell death induced by HIV-1-encoded proteins. AB - In most examples of physiological or pathological cell death, mitochondrial membrane permeabilization (MMP) constitutes an early critical event of the lethal process. Signs of MMP that precede nuclear apoptosis include the translocation of cytochrome c and apoptosis-inducing factor (AIF) from mitochondria to an extra mitochondrial localization, as well as the dissipation of the mitochondrial transmembrane potential. MMP also occurs in HIV-1-induced apoptosis. Different HIV-1 encoded proteins (Env, Vpr, Tat, PR) can directly or indirectly trigger MMP, thereby causing cell death. The gp120/gp41 Env complex constitutes an example for an indirect MMP inducer. Env expressed on the plasma membrane of HIV 1 infected (or Env-transfected) cells mediates cell fusion with CD4/CXCR4 expressing uninfected cells. After a cell type-dependent latency period, syncytia then undergo MMP and apoptosis. Vpr exemplifies a direct MMP inducer. Vpr binds to the adenine nucleotide translocator (ANT), a mitochondrial inner membrane protein which also interacts with apoptosis-regulatory proteins from the Bcl 2/Bax family. Binding of Vpr to ANT favors formation of a non-specific pore leading to MMP. The structural motifs of the Vpr protein involved in MMP are conserved among most pathogenic HIV-1 isolates and determine the cytotoxic effect of Vpr. These data suggest the possibility that viruses employ multiple strategies to regulate host cell apoptosis by targeting mitochondria. PMID- 11193033 TI - Morphologic, biochemical and molecular mitochondrial changes during reperfusion phase following brief renal ischemia. AB - Ischemia/reperfusion of organs and cells induces apoptosis through a complicated series of changes in mitochondria, mainly the generation of oxygen free radicals, permeability transitions, calcium translocations, and release of apoptogenic factors such as cytochrome c and Bcl-2 family members. The liberation of these factors occurs very early after reoxygenation and it has been assumed that it takes place without any structural alteration of the mitochondrial membranes. The aim of this study was to detect ultrastructural changes of mitochondria in the initial stages of reperfusion at the time when Bcl-2 and succinic dehydrogenase, located in the outer and inner membranes, respectively, were released. Ischemia/reperfusion was produced in adult rats by clamping one renal artery for 60 min and reoxygenating for 60, 120, 180, and 240 min. A model of chemical hypoxia with intra-arterial 50 mM sodium azide served as comparison, allowing free blood flow for 30, 60, 120 and 180 min. Light and electron microscopy, immunostaining for Bcl-2, and enzyme histochemistry for succinic dehydrogenase were performed. Our results showed mitochondrial swelling, rupture of inner and outer membranes, and leakage of mitochondrial matrix into the cytoplasm in ischemia after 120 min of reperfusion. Bcl-2 immunoreactivity and focal lowering of SDH reactivity were also noted and became more pronounced at the same time that the mitochondrial ultrastructure demonstrated more evident changes including rupture of the inner and outer membranes. Our studies seem to indicate that in early ischemia-reperfusion and in chemical hypoxia-induced apoptosis, the earliest ultrastructural changes take place in mitochondria and that swelling and rupture of mitochondrial membranes occur in parallel with the loss of Bcl-2 and SDH activity. PMID- 11193034 TI - Role of ECM remodeling in thyroid hormone-dependent apoptosis during anuran metamorphosis. AB - Programmed cell death or apoptosis is an important aspect in organogenesis and tissue remodeling. It is precisely controlled both temporally and spatially during development. Amphibian metamorphosis is an excellent model to study developmental control of apoptosis in vertebrates. This process involves the transformation of essentially every organ/tissue as tadpoles change to frogs, yet is controlled by a single hormone, thyroid hormone (TH). Although different organs and tissues undergo vastly different developmental changes, including de novo development and total resorption, most require apoptotic elimination of at least some cell types. Such properties and the dependence on TH make frog metamorphosis a unique model to isolate and functionally characterize genes participating in the regulation of tissue specific cell death during organ development in vertebrates. Indeed, molecular studies of the TH-dependent gene regulation cascade have led to the discovery of a group of genes encoding matrix metalloproteinases (MMPs) participating in metamorphosis. In vivo and in vitro studies have provided strong evidence to support a role of MMP-mediated remodeling of the extracellular matrix in regulating apoptotic tissue remodeling during metamorphosis. PMID- 11193035 TI - A caspase-independent cell clearance program. The LEI/L-DNase II pathway. AB - The discovery of caspase-mitochondrial pathway counts as one of the most important discovery in apoptosis biochemistry. Today, however, we begin to recognize its limits. Inhibition of caspase does not prevent cell death in many mammalian models. Targeted disruption of caspases does not impair every type of apoptosis. Other pathways, caspase independent, are now described. Here we present one of these pathways. It is a serine-protease dependent pathway and its key event is the transformation of LEI (a serine protease inhibitor) into L-DNase II (an endonuclease). When using this apoptotic pathway the cell activates, at the same time, its endonuclease activity (L-DNase II appears) and its protease activity (there is a release of inhibition of proteases). PMID- 11193036 TI - Role of apoptosis in the response of lung carcinomas to anti-cancer treatment. AB - Resistance of tumor cells to treatment often accounts for the failure of traditional forms of anti-cancer therapy. It is well known that tumors from the same histological group and stage of development are highly heterogeneous in their sensitivity to therapy. Among the factors that can influence tumor sensitivity are DNA repair capacity, distribution of cells throughout the cell cycle, proliferation potential, etc. In many cases, anti-cancer therapy eliminates tumor cells via apoptosis, an active form of cell death characterized by cell shrinkage and the removal of cells in a neat, orderly fashion. However, this process is not always efficient. In the present review, the precise role that apoptosis plays in the response of lung carcinomas to chemotherapy and radiation treatment is discussed. PMID- 11193037 TI - The central role of phosphatidylserine in the phagocytosis of apoptotic thymocytes. AB - Apoptotic thymocytes inactivate the aminophospholipid translocase, which transports phosphatidylserine (PS) to the inner leaflet of the plasma membrane, and activate the scramblase, which randomizes phospholipids across the membrane and brings PS to the cell surface. Although different macrophages use at least two different systems to recognize and engulf apoptotic thymocytes, both systems recognize PS on the apoptotic target. Thymocytes treated with Ca2+ and ionophore to inactivate the translocase and activate the scramblase immediately expose PS on their surface and are immediately recognized and phagocytosed. These targets, on which PS has been artificially exposed, are recognized by the PS exposed on their surface. However, they apparently also engage the vitronectic receptor, a lectin-like receptor and CD14. All of these receptors are implicated in the phagocytosis of apoptotic thymocytes, suggesting that loss of asymmetry and/or exposure of PS is sufficient to generate the ligands recognized by those receptors. The role of PS is not confined to the target cell surface, however. PS is constitutively exposed on the surface of macrophages and is as necessary for apoptotic cell engulfment as is recognition of PS on the target cell surface. PMID- 11193038 TI - Opsonization of apoptotic cells. Implications for uptake and autoimmunity. AB - As a part of innate immunity, soluble host proteins called opsonins, which include complement ligands and immunoglobulins, initially coat microorganisms that penetrate the mammalian sterile milieu. The main purpose of opsonization is to allow subsequent clearance of opsonized particles by specific receptors on the surface of leukocytes. Similarly, several proteins that may act as opsonins and have a role in uptake of apoptotic cells and bodies include thrombospondin I, the complement system, beta 2GPI, immunoglobulins, CRP, and some unidentified others. The surface changes that lead to opsonization include the appearance of phosphatidylserine that acts as an activator molecule for some known opsonins as the complement system and beta 2GPI. The consequence of altered opsonization is demonstrated by the development of autoimmunity in C1q deficient mice, and the pro-inflammatory response by macrophages ingesting apoptotic cell opsonized by an autoantibody. PMID- 11193039 TI - HIV, cytokines and programmed cell death. A subtle interplay. AB - HIV infection is marked by the progressive destruction of the CD4 T lymphocyte subset, an essential component of the immune system and a vital source of cytokines required for differentiation of natural killer (NK) and gamma delta T cells, for maturation of B lymphocytes into plasmocytes, and for differentiation of CD8+ T cells into virus-specific cytotoxic T lymphocytes. CD4 T lymphocytes are also a source of chemokines which control migration of lymphocytes to the site of infection and which also inhibit HIV entry into CD4-expressing targets. Continuous production of viral proteins leads to an unbalanced immune activation and to the triggering of apoptotic programs, turning mononuclear cells, including CD4 T cells, CD8 T cells and APC, into effectors of apoptosis, leading to fratricidal destruction of healthy uninfected cells expressing the death receptors. Inappropriate PCD is also responsible for the disappearance of T helper cells primed for type-1 cytokine synthesis, thus contributing to the lack of survival factors which could prevent spontaneous lymphocyte apoptosis. Under potent anti-retroviral therapies, a significant decrease in spontaneous, TCR- and CD95-induced lymphocyte apoptosis is observed, concomitant with a partial quantitative and qualitative restoration of the immune system in treated patients. However, owing to the suppressive effect of anti-retroviral drugs on physiological apoptosis, these therapies are associated with alteration of TNF alpha-regulated T cell homeostasis, leading to an accumulation in the blood of T cells primed for TNF-alpha synthesis, and contributing to the development of a new syndrome associated with these treatments, the lipodystrophy syndrome. PMID- 11193040 TI - Quantitation of CD95 and CD95L mRNA expression in chronic and acute HIV-1 infection by competitive RT-PCR. AB - Human immunodeficiency virus-type 1 (HIV-1) infection is characterized by increased immune cell apoptosis. Apoptosis can be triggered by signals that arise from within the cell, or by signals that are elicited by binding of extracellular "death ligands" to their "death receptors," most of which belong to the tumor necrosis factor (TNF)-receptor family, such as CD95 (Fas/Apo-1). In immune cells the oligomerization of CD95, induced by its ligand CD95L, and the recruitment of different intracytoplasmic molecules that in turn activate FLICE/caspase 8 are crucial. To study the role of CD95/CD95L interactions during HIV-1 infection, we developed an original method based upon quantitative-competitive (QC) RT-PCR that allowed us to quantify the amounts of mRNA coding for the total (tCD95) and membrane (mCD95) forms of CD95. We first studied the expression of different forms of CD95 mRNA in a classical model of chronic HIV infection using two infected cell lines of different origin--lymphocytic (ACH-2) or monocytic (U1). We have shown that infected cells of monocytic origin preferentially produce the "protective" (soluble) form of CD95, and no detectable CD95L mRNA, while lymphoid cells produce more mRNA for the membrane form of CD95 (which triggers apoptosis) along with low but detectable amounts of CD95L mRNA. One can hypothesize that a complex balance exists between pro-apoptotic events, perhaps triggered by the host to limit viral production, and anti-apoptotic events likely triggered by the virus to increase its production and survival. In cells of monocytic origin, which act as a reservoir for the virus, the anti-apoptotic molecules are favored; in cells of lymphocytic origin, molecules with an apoptotic meaning are prevalent. PMID- 11193042 TI - Tissue biology of apoptosis. Ref-1 and cell differentiation in the developing retina. AB - Programmed cell death by apoptosis plays a major role in neurogenesis. The sensitivity to apoptosis in developing nervous tissue is strongly dependent on cell interactions taking place within a highly structured environment, composed of various cell types at distinct stages of differentiation. In this article, we review evidence gathered both in vivo and in a histotypical retinal explant preparation in vitro that the bifunctional AP endonuclease/redox factor Ref-1 (HAP1, APE, APEX) may be an anti-apoptotic protein associated with cell differentiation in the developing retina. PMID- 11193041 TI - The complexity of TNF-related apoptosis-inducing ligand. AB - One of the major goals of researchers in the field of apoptosis is to understand the molecular mechanisms of the various components of the apoptotic pathways, with the hope to identify targets for novel cancer therapies. The discovery of a TNF-related, apoptosis-inducing ligand, TRAIL, that kills transformed cells with great specificity in vitro, has provided the hope that TRAIL may be used to induce cell death in tumor cells without affecting normal tissues. However, TRAIL signaling is very complex and a clear understanding of its function is necessary before it can be used in cancer therapy. Complexity of TRAIL-induced signaling is apparent from its ubiquitous expression, its ability to interact with five receptors, and its tumor-selective induction of apoptosis. The signaling events that mediate the tumor selectivity of TRAIL-induced apoptosis and the biological functions of each of the TRAIL receptors are not well characterized. This review will focus on the complexity of TRAIL and the role of c-FLIP in mediating TRAIL function. PMID- 11193043 TI - Modulation of cell death in the rat thymus. Light and electron microscopic investigations. AB - In mammals, the thymus is the primary central organ of the lymphoid system; after birth, it progressively diminishes in size, undergoing gradual atrophy. Physiological maturation and/or involution of the thymus may be accelerated by endogenous or exogenous factors. Exposure to extremely low frequency EMF seems to interfere with thymic cell death. Data suggest that, in the rat model, a prolonged exposure to 50 Hz electric and magnetic fields, independently from field strength, seems to affect thymic cell death and possibly thymic physiology, since alterations in the balance of cell death and other parameters such as mitoses might interfere with the positive and negative selection of thymocytes and with the immunosurveillance properties of the thymus. PMID- 11193044 TI - The role of the pro-apoptotic Bcl-2 family member bim in physiological cell death. AB - Apoptosis, an evolutionarily conserved process for killing unwanted cells in multicellular organisms, is essential for normal development, tissue homeostasis and as a defense against pathogens. The control of apoptosis is of considerable importance for clinical medicine, as its deregulation can lead to cancer, autoimmunity or degenerative diseases. We have disrupted the Bim gene in the mouse and demonstrated that it plays a major and non-redundant role in embryogenesis, in the control of hematopoietic cell death, and as a barrier against autoimmunity. PMID- 11193045 TI - Evolution of functions within the p53/p63/p73 family. AB - Even though the tumor suppressor gene p53 is highly important in human cancer, as indicated by the fact that it is mutated in about 50% of cases, up to a few years ago no similar proteins had been identified. Recently, two p53 homologues have been identified, p73 and p63, with high amino acid identity suggesting similar functions. Indeed, like p53, p73 as well (i) can bind mdmX, mdm2, p300/CAF and adenovirus E4-orf6 proteins, (ii) can trigger several promoters including p21, bax, mdm2, gadd45, cyclin G, IGFBP3, 14-3-3 sigma, (iii) is able to trigger cell death, (iv) is involved in the DNA damage response, although through a different pathway. Here we analyze the data present in the literature in search of diverging pathways among the p53, p63, p73 family. Both p63 and p73 present two significant structural peculiarities: the presence of an extended non-conserved C terminus containing a sterile alpha motive (SAM), typical of developmental proteins, and the presence of number of different splicing isoforms differing in the N-terminus or in the absence of the transactivation domain (delta N forms), acting as dominant negative. The mouse knockout of p63 and p73, unlike the ones for p53, shows developmental abnormalities; p63 and p73 are rarely mutated in human cancers; both genes are regulated in different differentiation models. This strongly suggests the involvement of p63 and p73 in development. A picture is emerging showing a gradient of function among p53, p73, p63 ranging from tumor suppression to development. PMID- 11193046 TI - Microarray techniques in pathology: tool or toy? AB - Microarray technology allows the simultaneous analysis of up to thousands of different genes in histological or cytological specimens. Although microarray technology has so far mainly been applied in the research setting, its clinical application in pathology is expected in the foreseeable future. This paper presents an overview of the technical "ins and outs" of microarray technology, and discusses several putative applications in diagnostic pathology, which include tumour classification, the prediction of responses to certain chemotherapeutical or hormonal agents, the biological staging of tumours, the risk assessment of premalignant lesions, and the detection of microorganisms. PMID- 11193047 TI - Cell receptors and cell signalling. AB - All cells in a multicellular organism are constantly exposed to a variety of extracellular signals that they need to interpret and translate into an appropriate response to their environment. These signals can be soluble factors generated locally (for example, synaptic transmission) or distantly (for example, hormones and growth factors), ligands on the surface of other cells, or the extracellular matrix itself. To achieve this, cells maintain a diversity of receptors on their surface that respond specifically to individual stimuli. These receptors fall into families, based primarily on the way in which they generate the intracellular signals that give rise to the particular functional responses. Moreover, the activity of a given receptor can be modulated by other signalling pathways in a variety of ways, generating the flexibility required of such a complex system. This review aims to describe the function of the major classes of receptor, including G protein coupled receptors, receptor tyrosine kinases, ligand gated ion channels, integrins, and cytokine receptors, and to demonstrate the "crosstalk" that exists between these systems. PMID- 11193048 TI - Thrombophilia, polymorphisms, and vascular disease. AB - Thrombophilia traditionally refers to rare inherited defects leading to enhanced coagulation, especially of the venous system. In recent years, a broader search for genetic polymorphisms of prothrombotic genes has been carried out to determine the relative impact on venous and arterial thrombosis. The bulk of evidence is drawn from numerous, often small, heterogeneous, case control association studies, with a variety of end points (deep venous thrombosis, myocardial infarction, or stroke). The data are often conflicting and inconclusive with only factor V Leiden and prothrombin polymorphisms having clear associations with venous thrombosis. Many of the polymorphisms interact with established cardiovascular risk factors, in particular smoking, to increase greatly the risk of a thrombotic episode. Future studies will need to consider the confounding factors of sample size, race, and clinical end points as well gene-environment interactions. PMID- 11193049 TI - Plasminogen activator system, vascular endothelial growth factor, and colorectal cancer progression. AB - AIMS: To plasminogen activator system (PAS) consists of the plasminogen activators (urokinase (uPA) and tissue-type (tPA) plasminogen activators), the uPA receptor (uPAR), and the plasminogen activator inhibitors (PAI-1 and PAI-2). Plasminogen activators activate plasminogen to plasmin, which can break down extracellular matrix (ECM) components. Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cells and is involved in angiogenesis. VEGF has been shown to upregulate uPA and this may facilitate tumour angiogenesis further. METHODS: PAS components and VEGF were determined by enzyme linked immunosorbent assay (ELISA) in paired colorectal tumour and normal tissue (n = 50) and correlated with pathological staging. RESULTS: uPA, uPAR, PAI-1, and VEGF values were significantly higher in tumour tissue (for example, tumour uPA: median, 2.3 (range, 0.1-6.7) ng/mg protein v normal uPA: median, 0.2 (range, 0-2.6) ng/mg protein). tPA was significantly higher in normal mucosa and there was no difference in PAI-2. uPA, uPAR, PAI-1, and VEGF values significantly correlated with each other and with Dukes's staging (uPA in adenomas: median, 0.42 (range, 0.1-1.2) ng/mg protein; upA in Dukes's B tumours: median, 2.1 (range, 0.4-4.3) ng/mg protein; and uPA in Dukes's D tumours: median, 4.0 (range, 3.7-4.2) ng/mg protein) and lymphatic invasion. In addition PAI-1 also correlated with tumour size and differentiation. CONCLUSION: The involvement of the PAS and VEGF in colorectal cancer appears to be complex. uPA, uPAR, PAI-1, and VEGF were upregulated in tumour tissue and this correlated with Dukes's staging and lymphatic invasion. PMID- 11193050 TI - Imbalances of chromosome 17 in medulloblastomas determined by comparative genomic hybridisation and fluorescence in situ hybridisation. AB - AIMS: To investigate the status of chromosome 17 in a series of medulloblastomas using comparative genomic hybridisation (CGH) and fluorescence in situ hybridisation (FISH). METHODS: Frozen tissue and formalin fixed, paraffin was embedded tissue from 27 medulloblastomas were analysed by CGH and FISH, respectively. CGH ratio profiles for chromosome 17 were compared with the results of FISH, for which loss or gain of 17p or 17q was assessed in two distinct ways using a combination of differentially labelled subtelomeric and centromeric probes and analysing 200 nuclei in each tumour. RESULTS: CGH revealed imbalances consistent with isochromosome 17q in eight of 27 tumours. Either loss of 17p or gain of 17q was identified in a further nine tumours, whereas 10 tumours were apparently balanced. Using control results from preparations of paraffin wax embedded tonsils, thresholds for the detection of abnormalities by FISH were established, either by determining the dominant pattern of signals in each case, or the mean ratio of subtelomeric to centromeric signals. Results by CGH and FISH were concordant in 21 of 27 tumours. In the remainder, most discrepancies related to methodological differences. CONCLUSIONS: CGH has a role in disclosing common, genome wide chromosomal gains or losses in tumours, the clinical relevance of which can then be studied in large archival series of paraffin wax embedded tumours using FISH. PMID- 11193051 TI - The imprinted H19 gene is a marker of early recurrence in human bladder carcinoma. AB - AIMS: To investigate the expression of the imprinted oncofetal H19 gene in human bladder carcinoma and to examine the possibility of using it as a tumour marker, similar to other oncofetal gene products. METHODS: In situ hybridisation for H19 RNA was performed on 61 first biopsies of bladder carcinoma from Hadassah Medical Centre in Jerusalem. The intensity of the reaction and the number of tumour cells expressing H19 in each biopsy were evaluated in 56 patients, excluding biopsies with carcinoma in situ. The medical files were searched for demographic data and disease free survival. RESULTS: More than 5% of cells expressed H19 in 47 of the 56 (84%) biopsies. There was a decrease in the number of cells expressing H19 with increasing tumour grade (loss of differentiation) (p = 0.03). Disease free survival from the first biopsy to first recurrence was significantly shorter in patients with tumours having a larger fraction of H19 expressing cells, controlling for tumour grade. This was also supported by the selective analysis of tumour recurrence in patients with grade I tumours. CONCLUSIONS: It might be possible to use H19 as a prognostic tumour marker for the early recurrence of bladder cancer. In addition, for the gene therapy of bladder carcinoma that is based on the transcriptional regulatory sequences of H19, the expression of H19 in an individual biopsy could be considered a predictive tumour marker for selecting those patients who would benefit from this form of treatment. PMID- 11193053 TI - A unique junctional palindromic sequence in mitochondrial DNA from a patient with progressive external ophthalmoplegia. AB - A polymerase chain reaction (PCR) based procedure was modified to determine the deletion of mitochondrial DNA (mtDNA). The protocol consists of coamplification both of deleted and wild-type segments of mtDNA using a long PCR technique; evaluation of the deleted portion within the amplified DNA segments by restriction enzyme digestion followed by densitometrical analysis; and direct subcloning into a plasmid vector for DNA sequencing. The procedure revealed a 5.3 kb deletion of mtDNA in the biopsied muscle tissue obtained from a patient clinically diagnosed with progressive external ophthalmoplegia. The 5' and 3' sequences at both sides of the breakpoint comprise a 17 bp palindrome and 5 bp tandem repeats, suggesting that the deletion might occur through slipped mispairing and other novel mechanisms. This improved procedure has the potential to detect deletions occurring in the entire length of mtDNA, and mighty be useful for clinical screening of progressive external ophthalmoplegia. PMID- 11193052 TI - Prediction of the interacting surfaces in a trimolecular complex formed between the major dust mite allergen Der p 1, a mouse monoclonal anti-Der p 1 antibody, and its anti-idiotype. AB - BACKGROUND: Two mouse monoclonal antibodies (mAbs) have been described recently; namely, mAb 2C7 (IgG2b kappa), which is directed against the major house dust mite allergen Der p 1, and mAb 2G10 (IgG1 kappa), which is an anti-idiotypic antibody raised against mAb 2C7. The anti-idiotype mAb 2G10 does not block the binding of mAb 2C7 to Der p 1, which means that mAb 2C7 can simultaneously bind to Der p 1 and to mAb 2G10, thereby generating a trimolecular complex consisting of antigen-idiotype-anti-idiotype. AIMS: To sequence and model the V region of the anti-idiotypic antibody mAb 2G10 to enable the prediction of the interacting surfaces in the trimolecular complex consisting of Der p 1-mAb 2C7-mAb 2G10. METHODS: DNA sequencing of mAb 2G10 was carried out and the Swiss Model and Swiss PDB-Viewer programs were used to build a three dimensional model of the trimolecular complex. RESULTS: Complementarity of shape and charge was revealed when comparing the protrusion of the previously determined Der p 1 epitope (Leu147-Gln160) with the cavity formed by the complementarity determining regions (CDRs) of mAb 2C7. Such complementarity was also observed between the mAb 2C7 epitope predicted to be recognised by mAb 2G10 (residues Lys19 from framework region 1 (FRW1) and Ser74-Gln81 from FRW3) and residues from the CDRs of mAb 2G10 (a negatively charged patch flanked by the residues Asp55H/Glu58H and Glu27L/Glu27cL). As expected, the location of the mAb 2C7 epitope recognised by mAb 2G10 does not appear to interfere with the binding of Der p 1 to mAb 2C7. CONCLUSION: Although the results obtained represent only an approximation, they nevertheless provide a rare insight into how an antigen (Der p 1) might bind to its antibody (mAb 2C7) while in complex with an anti-idiotype (mAb 2G10). PMID- 11193054 TI - Formic acid decalcification of bone marrow trephines degrades DNA: alternative use of EDTA allows the amplification and sequencing of relatively long PCR products. PMID- 11193055 TI - The quality of expectation: healing, palliation or disappointment. PMID- 11193056 TI - To cure or not to cure, that is not the question. PMID- 11193057 TI - Is early management of acoustic neuroma important? PMID- 11193058 TI - Behavioural phenotypes. PMID- 11193059 TI - Expectations and quality of life of cancer patients undergoing radiotherapy. AB - Expectations, real or false, affect the way patients respond to their illnesses. We assessed therapy-related expectations in relation to global quality of life in 55 cancer patients before and after radiotherapy. Factor analysis indicated that therapy-related expectations come into three broad categories--pain/emotional control, healing and tumour/symptom control. 35 patients expected 'healing' even though curative treatment was intended in only 19 and all patients had been fully informed. The expectation of healing was associated with high quality of life, and the same was true of perception of healing after radiotherapy. In the group as a whole, quality of life was little altered by radiotherapy, but it became substantially worse in those patients who had expected healing but perceived that this had failed, even though physician-assessed Karnofsky status did not change. These findings indicate that the expectation of healing, in cancer patients, is a component of a good global quality of life, whereas more limited expectations (pain control, tumour control) relate to lower quality of life. Patients' expectations deserve further study as a novel approach to improving care. PMID- 11193060 TI - Decision support systems. PMID- 11193061 TI - Haemothorax via an intact diaphragm. PMID- 11193062 TI - Acromegaly, primary thyrotoxicosis, a dense left hemiparesis and a right internal carotid aneurysm. PMID- 11193063 TI - Rupture of the ankle extensor retinaculum in a dancer. PMID- 11193064 TI - Malign anterior knee pain. PMID- 11193065 TI - Group A streptococcal meningitis with an infected BCG scar. PMID- 11193066 TI - RSM 1907: the acceptance of specialization. PMID- 11193067 TI - The case of Jane Anderson, Portobello, 1889-1914. PMID- 11193068 TI - Predictions for psychiatry. PMID- 11193069 TI - Hidradenitis suppurativa. PMID- 11193070 TI - Hospitalists for the NHS. PMID- 11193071 TI - Whiplash: a double injury. PMID- 11193072 TI - Clinical diagnosis and the function of necropsy. PMID- 11193073 TI - Molecularly imprinted microparticles for capillary electrochromatographic enantiomer separation of propranolol. AB - Molecularly imprinted microparticles imprinted against (S)-propranolol were synthesised and studied for use in capillary electrochromatographic separation of propranolol enantiomers. The imprinted microparticles were in the size range of 0.2-0.5 micron as determined by scanning electron microscopy. The microparticles were suspended, in high concentration, in the electrolyte and used to perform enantiomer separation by a partial filling technique. PMID- 11193074 TI - Enhancement of luminol chemiluminescence by cysteine and glutathione. AB - Cysteine enhancement of cobalt(II)-catalysed chemiluminescence of hydrogen peroxide and luminol occurs in carbonate buffer (but not in borate buffer), whether cysteine mixes with hydrogen peroxide before it mixes with luminol cobalt(II) or vice versa. Enhancement was measured by the ratio of the signals in the presence and absence of cysteine; standard errors were generally < 5% of the mean ratio. Cystine in sufficiently acidic solution also enhances the chemiluminescence but otherwise diminishes the emission. The emission is also inhibited by glutathione. A mixed solution of cysteine and cystine gives rise to enhanced signals. In all the above cases, enhancement occurs only in the presence of a cobalt(II) catalyst. Luminol-peroxynitrite chemiluminescence is enhanced by cysteine and by glutathione without the presence of a catalyst. PMID- 11193075 TI - A fluorescent-labeled oligopeptide for monitoring PKA-mediated phosphorylation. AB - A fluorescent-labeled oligopeptide (DACM-CLRRASLK-fluorescein), containing a consensus amino acid sequence (RRXSL) of cyclic AMP (cAMP) dependent protein kinase A (PKA) substrate-proteins, was designed. The fluorescent peptide was a good substrate of PKA, and the phosphorylation of its serin residue caused an intensive change in fluorescent intensity. We expect that the peptide will be useful as a fluorescent indicator for monitoring PKA activity in living cells. PMID- 11193076 TI - Photoelectrochemistry as a novel strategy for DNA hybridization detection. AB - The special properties of ssDNA and dsDNA molecules in structure and electric behavior, may offer us some new ideas for the fabrication of genosensors and DNA chips. In this work, the photoelectrochemical method was firstly employed to characterize the photoelectric behavior of a ssDNA probe electrode, which was prepared with the self-assembly technique, and its resulting dsDNA electrode. The obvious decrease in the photocurrent of the dsDNA modified electrode at open potential or a bias voltage indicated that photoelectrochemistry was another useful method for DNA hybridization detection. Using the special design of ssDNA probes, we attempt to discuss further the relationship between the properties of DNA molecules and their photoelectric behaviors. In addition, the electrochemical impedance method was employed to verify the occurrence of some modifications over the electrode interface before and after the hybridization event. PMID- 11193077 TI - Tetraethylammonium tetrafluoroborate: a novel electrolyte with a unique role in the capillary electrophoretic separation of polyphenols found in grape seed extracts. AB - A capillary electrophoretic method for resolving phenolic compounds found in grape seed extracts was developed using a quaternary ammonium salt as the main electrolyte solution. Seven polyphenols were separated and identified. The separation mechanism seems to involve association between quaternary ammonium cations and the polyphenols. Migration times roughly correlate with the size of the known phenols. The role of the alkyl substituents on the quaternary ammonium ions was investigated and is discussed. The method of analysis proposed herein exhibits high reproducibility in terms of migration times for a complex mixture using a single component background electrolyte. PMID- 11193078 TI - Enzymatic activity measurement of phospholipid hydroperoxide glutathione peroxidase by capillary electrophoresis. AB - Based on the separation of 1-palmitoyl-2-(13-hydroperoxy-cis-9,trans-11 octadecadienoyl)-L-3- phosphatidylcholine (PC-OOH) and 1-palmitoyl-2-(13-hydroxy cis-9,trans-11-octadecadienoyl)-L-3- phosphatidylcholine (PC-OH) and the quantitative determination of PC-OH, the enzymatic activity of phospholipid hydroperoxide glutathione peroxidase (PHGPx) can be measured by capillary electrophoresis. The separation was carried out in a fused-silica capillary (30 cm x 100 microns id) at 15 kV positive voltage. Sodium borate (100 mM; pH = 8.4) was used as the running buffer, and the photodiode array detector wavelength was 232 nm. The determination can be completed in 5 min. The detection limit was 5 pmol; and the relative standard deviation (RSD) of the peak area was less than 1% with an average recovery of 98.6%. Compared with traditional methods such as HPLC and spectrophotometry, it is faster and more convenient. Using capillary electrophoresis, the enzymatic activities of PHGPx expressed by the rice PHGPx gene in E. coli. M15 was determined as 1.25 x 10(-5) mumol min-1, and the specific activity of partially purified trans-gene PHGPx was 3.1 x 10(-2) mumol min-1 per mg. The stability of the trans-gene PHGPx was also studied. PMID- 11193079 TI - Development of a rapid screening technique for organochlorine pesticides using solvent microextraction (SME) and fast gas chromatography (GC). AB - A novel, fast screening method for organochlorine pesticides (OCPs) in water samples has been developed. Total analysis time was less than 9 min, allowing 11 samples to be screened per hour. The relatively new technique of solvent microextraction (SME) was used to extract and preconcentrate the pesticides into a single drop of hexane. The use of a conventional carbon dioxide cryotrap was investigated for introduction of the extract onto a micro-bore (0.1 mm) capillary column for fast GC analysis. A pulsed-discharge electron capture detector was used which yielded selective and sensitive measurement of the pesticide peaks. Fast GC conditions were optimised and tested with the previously developed SME procedure. Calibration curves yielded good linearity and concentrations down to 0.25 ng mL-1 were detectable with RSD values ranging from 12.0 to 28% and LOD for most OCPs at 0.25 ng mL-1. Spiked river water samples were tested and using the developed screen we were able to differentiate between spiked samples and samples containing no OCPs. PMID- 11193080 TI - Determination of airborne methyl isocyanate as dibutylamine or 1-(2 methoxyphenyl)piperazine derivatives by liquid and gas chromatography. AB - The usefulness of a glass fibre filter method to collect airborne methyl isocyanate (MIC) was studied in laboratory experiments and in a workplace during manufacture of mineral wool insulation material. Filter collection was based on derivatisation in situ with 1-(2-methoxyphenyl)piperazine (2MP). 2MP impinger sampling was also evaluated in the workplace. Impinger sampling with dibutylamine (DBA) was used as an independent method. The samples were analysed by liquid and gas chromatography using various detection techniques: mass spectrometry, ultraviolet and electrochemical detection (LC-MS, LC-UV, LC-EchD and GC-MS). The sampling efficiency of 2MP filters for MIC varied with the origin of the glass fibre filter. Two Whatman filters (diameter 25 mm) with altogether 21 mumol of 2MP collected 100% of 9.8 micrograms of MIC during 30 min at an airflow rate of 1 l min-1. The workplace measurements were performed at two concentration levels, 0.003 and 0.09 mg m-3. The theoretical amounts of derivatisation reagent were 42 mumol (2MP filter), 52 mumol (2MP impinger) and 100 mumol (DBA). MIC concentrations were 20% lower by the 2MP methods compared with the DBA method (statistically significant difference). Breakthrough was 6% for the DBA method and 9% for the 2MP impinger method. To trap both MIC and isocyanic acid, which was also present in the workplace samples, a tenfold molar amount of 2MP reagent was used. The precision of sample preparation, expressed as relative standard deviation, was 3.5% (0.17 microgram ml-1, n = 6). The precision of sampling in the workplace was 15% (0.002 mg m-3, n = 6). The limit of quantification was 0.0006 mg m-3 for 30 l of air by the 2MP impinger method and 0.03-0.05 mg m-3 by the 2MP filter method. Hence, airborne MIC can be determined using 2MP as derivatisation reagent. Impinger sampling is preferable when low concentration levels are expected. PMID- 11193081 TI - Description and validation of an analytical method for the determination of paromomycin sulfate in medicated animal feeds. AB - A procedure for the extraction of paromomycin from different animal feed matrices (rabbit, chicken, pig feeds) and its subsequent determination via a reversed phase ion-pair HPLC separation coupled with pulsed amperometric detection is described. The procedure optimised in terms of the extracting solvent and the solid phase extraction stationary phase allows the total recovery of the aminoglycoside antibiotic. The criteria used for the validation of the analytical method applied to the cited matrices are the linear dynamic range of the response, the detection limit, the repeatability, the intermediate repeatability and the accuracy. A comparison with a method described in the literature for the bulk analysis of this antibiotic is made. PMID- 11193082 TI - Determination of 4-nonylphenol and 4-octylphenol in human blood samples by high performance liquid chromatography with multi-electrode electrochemical coulometric-array detection. AB - Alkylphenols can affect human health because they disrupt the endocrine system. In this study, an analytical method for determining trace amounts of 4 nonylphenol (NP) and 4-octylphenol (OP) in human blood samples was developed. Reversed-phase HPLC with multi-electrode electrochemical coulometric-array detection was used for the determination of NP and OP in plasma and serum samples prepared with a solid-phase extraction method. The separation was achieved using an isocratic mobile phase of 0.7% phosphoric acid-acetonitrile with a C18 reversed phase column. The detection limits of NP and OP were 1.0 and 0.5 ng ml 1, respectively. The recoveries of NP and OP added to human plasma samples were above 70.0% with a relative standard deviation of less than 15.5%. The method was found to be applicable to the determination of NP and OP in various human blood samples such as serum and plasma. PMID- 11193083 TI - Binding patterns of co-existing aluminium and iron to human serum transferrin studied by HPLC-high resolution ICP-MS. AB - Serum transferrin (Tf) is an iron-binding glycoprotein. Aluminium in the blood is bound to the transferrin. In the present study, the chemical forms of co-existing Al and Fe bound to human serum Tf were studied by combined on-line HPLC and high resolution ICP-MS (HPLC-HR-ICP-MS). Samples were subjected to HPLC equipped with an anion-exchange column. The levels of 27Al, 56Fe and 32S, which are interfered with by polyatomic ions such as 13C14N+, 12C15N+ and 12C14N1H+, 40Ar16O+ and 40Ca16O+, and 16O2+, respectively, when using quadrupole ICP-MS, were monitored simultaneously by HR-ICP-MS at a resolution of m/delta m = 3000. Al added to apo Tf as Al-citrate was preferentially bound to the N-lobe site almost selectively. Al in serum from a healthy person without any in vitro Al spike was present both as AlN-Tf and AlN,FeC-Tf. The chemical states were reproduced in the apo-Tf solution supplemented with Fe (Fe/Tf ratio = 0.6) and Al (Al/Tf ratio = 1) successively. The 32S level was useful for monitoring the protein levels in the HPLC eluate. The clean-up column procedures employed reduced the detection limit for 27Al to 0.1 microgram l-1 (3SB) at the middle resolution. PMID- 11193084 TI - Determination of triazine herbicides in foods with liquid chromatography mass spectrometry. AB - Eight residual triazine herbicides and three metribuzin metabolites in foods were determined by liquid chromatography mass spectrometry (LC-MS) with an atmospheric pressure chemical ionization (APCI) interface, under both positive and negative ion modes. Herbicides were extracted with acetonitrile, and no cleanup procedure was adopted in this method. Four foods were spiked with eight herbicides and three metabolites at 0.05 ppm. The average recoveries of these herbicides usually ranged from 82 to 99% and the relative standard deviations were usually around 10%. These results suggest that LC-MS with APCI can be used to determine residues of triazine herbicides in foods. PMID- 11193085 TI - Improved measurement of iodine in food samples using inductively coupled plasma isotope dilution mass spectrometry. AB - A new ICP-MS method for the determination of iodine in food samples is presented. The method makes use of a new miniature cyclonic spray chamber and a concentric glass nebulizer that is designed for low sample uptakes and is operated in a self aspirating mode. As a consequence the wash-out was accelerated over conventional systems. This configuration allows the direct determination of iodine in mineralized solutions following digestion with nitric acid only. No strong oxidizing reagents such as perchloric acid or lengthy sample preparation were necessary to alter the chemical form of potentially volatile species. The isotope dilution technique using the long-lived isotope 129I was applied to obtain freedom from matrix effects. The present study reports on results for total iodine in selected nutritional and biological reference materials and makes a comparison with instrumental neutron activation analysis. PMID- 11193086 TI - The quantification of potassium using a quartz crystal microbalance. AB - N,N'-dibenzyl-4,13-diaza-18-crown-6 (A) and bis[(benzo-15-crown-5)-4'-ylmethyl] pimelate (B) were tested as coatings for two piezoelectric crystals for potassium quantification. Both sensors showed stability, reversibility and sensitivity characteristics that allowed their use in quantitative analysis. However, compound A is much more sensitive to potassium than B. Compound A also shows a larger relative sensitivity for potassium with regard to sodium than B. A pharmaceutical sample of known composition was analysed both by an acoustic wave sensor with a crystal coated with compound A and by conductivity. No statistically significant difference in the median of the results was found (alpha = 0.05), although precision is superior for the conductivity methodology. Performance of the sensor in terms of frequency stability and selectivity was improved by the incorporation of PVC, a plasticizer and a lipophilic salt in the coating composition. Limits of detection found for potassium were 1.92 ppm, or 1.75 ppm for a crystal with a frequency decrease due to coating of 2.9 kHz or 3.9 kHz, respectively. Selectivity coefficients (fixed interference 80 ppm) for potassium over Na, Ca, Al, Zn, Mg, and Fe ranged from 0.103 to 0.332. PMID- 11193087 TI - Phasor transform to extract glucose and ascorbic acid data in an amperometric sensor. AB - A method for separating the signals from glucose and ascorbic acid on a single recognition surface using an ac immittance technique is presented. It is proposed that each oxidation process can be represented by a unique vector based on psi and YO, and that the concentration of each analyte can be determined by monitoring the change in the admittance magnitude in the direction of the characteristic angle for that particular species. The total Faradaic admittance (YF,total) for all electroactive species present is given by a linear combination of the independent vectors from the different species. In the system tested, the analytes are glucose and ascorbic acid, the former being estimated via the measurand, hydrogen peroxide. Thus, one of the electroactive species (hydrogen peroxide) is not a bulk solution species, but is 'generated' in the enzyme matrix. The admittance measurements from ascorbic acid and the enzyme-generated hydrogen peroxide showed the characteristic phase angles of each oxidation signal, allowing for good spatial resolution. The behaviour of each of these analytes is presented and calibration curves tested. Based on the calibration curves and the basis vectors, samples containing both glucose and ascorbic acid were measured by transforming the measured total admittance from the complex Cartesian space into 'analyte space', where the X-Y axes are given by the basis vectors yEGHP,GOD and yAA,GOD, respectively. PMID- 11193088 TI - Optical biosensing of nitrite ions using cytochrome cd1 nitrite reductase encapsulated in a sol-gel matrix. AB - Nitrite is an important human health and environmental analyte. As such, the European Union (EU) has imposed a limit for nitrite in potable water of 0.1 mg l 1 (2.18 microM). In order to develop an optical biosensing system for the determination of nitrite ions in environmental waters, cytochrome cd1 nitrite reductase has been extracted and purified from the bacterium Paracoccus pantotrophus. The protein has been spectroscopically characterised in solution and important kinetic parameters of nitrite reduction of the cytochrome cd1 enzyme, i.e., Km, Vmax and kcat have been determined. The influence of pH on the activity of the cytochrome cd1 has been investigated and the results suggest that this enzyme can be used for the determination of nitrite in the pH range 6-9. Biosensing experiments with the cytochrome cd1 in solution suggested that the decrease in intensity of the absorption band associated with the d1 haem (which is the nitrite binding site), at 460 nm, with increasing nitrite concentrations would enable the measurement of this analyte with the optimum limit of detection. The cytochrome cd1 has been encapsulated in a bulk sol-gel monolith with no structural changes observed and retention of enzymatic activity. The detection of nitrite ions in the range 0.075-1.250 microM was achieved, with a limit of detection of 0.075 microM. In order to increase the speed of response, a sol-gel sandwich thin film structure was formulated with the cytochrome cd1. This structure enabled the determination of nitrite concentrations within ca. 5 min. The sol-gel sandwich entrapped cytochrome cd1 enzyme was found to be stable for several months when the films were stored at 4 degrees C. PMID- 11193089 TI - Single-use phosphorimetric sensor for the determination of nalidixic acid in human urine and milk. AB - A single-use phosphorimetric sensor to determine the germicide nalidixic acid is proposed. The sensing action is based on the absorption of the analyte into the sensing zone and the subsequent measurement of the phosphorescence intensity emitted by the analyte fixed in the sensor. This plane drop sensor is made up of a 3 x 1.6 cm sheet of the polyester Mylar as solid support, and a circular film 5 mm in diameter and 20 microns in thickness, formed by poly(vinyl chloride) and tributyl phosphate as the plasticizer, adhered to its surface. The sensor is introduced for 2 h into the sample solution, after which it is dried and the phosphorescence intensity is measured directly at lambda ex = 332 nm, lambda em = 412 nm, with a delay time of 0.15 ms and a gate time of 10 ms, under a dry nitrogen stream. The characteristic parameters of the construction of the sensing zone and of the processes of fixing the analyte along with the emission of phosphorescence were studied. The applicable concentration range was from 60 to 1500 ng ml-1, with a detection limit of 20 ng ml-1 and a precision of 2% expressed as relative standard deviation. The method was applied to the determination of nalidixic acid in milk and human urine with recoveries ranging between 96.0 and 103.7%. The calibration process was carried out by applying a mathematical method of finite elements that expresses the analytical signal as a function of the analyte concentration and equilibration time between the sensor and the sample solution. PMID- 11193090 TI - Modified microelectrodes and multivariate calibration for flow injection amperometric simultaneous determination of ascorbic acid, dopamine, epinephrine and dipyrone. AB - Flow injection amperometric quantification of ascorbic acid (AA), dopamine (DA), epinephrine (EP) and dipyrone (DI) in mixtures (in the microgram g-1 range) was successfully performed by using an array of microelectrodes with units modified by the electrodeposition of different noble metals, together with multivariate calibration analysis. The four groups of microelectrodes utilized included a pure gold electrode and electrodes modified by electrodeposition of platinum, palladium or a mixture of platinum + palladium. The array of microelectrodes was inserted in a flow cell and the amperometric data acquisition was performed with a four-channel potentiostat. The analysis of the resulting signals was carried out by a multivariate calibration method, using a group of 16 standard mixtures selected by a two-level factorial design. The analysis of synthetic samples and pharmaceutical compounds containing AA and DI led to very similar values to those obtained by the classical iodimetric analysis. The average absolute errors (in microgram g-1) calculated for each analyte were 0.3, 0.2, 0.4 and 0.4 for AA, DA, EP and DI, respectively. PMID- 11193091 TI - Electrochemical oxidation at carbon paste electrode of tacrine and 1 hydroxytacrine and differential pulse voltammetric determination of tacrine in pharmaceuticals and human urine. AB - The electrochemical oxidation of tacrine and its 1-OH-metabolite, has been studied by cyclic voltammetry and differential pulse voltammetry by using carbon paste electrodes. The peak current-concentration relationship was found to be linear up to 20 micrograms ml-1 with detection limits of 0.06 microgram ml-1 for tacrine and 0.18 microgram ml-1 for 1-OH-tacrine and quantitation limits of 0.20 microgram ml-1 for tacrine and 0.37 microgram ml-1 for 1-OH-tacrine. A method for determining tacrine by differential pulse voltammetry in pharmaceuticals and human urine, in the presence of 1-OH-tacrine, has been developed. PMID- 11193092 TI - Principal component analysis and cluster analysis for the characterization of dental composites. AB - Various experimental dental materials were characterized using chemometric methods. The main aim of the study was to ascertain which composite materials present the best properties for use in restorative dentistry. Bisphenol-alpha glycidyl methacrylate-based composites containing hydroxyapatite as a filler and a coupling agent were prepared using a photocuring polymerization procedure. Several chemical and mechanical properties of experimental composites were measured and the corresponding data were further studied using principal component analysis and cluster analysis. Results from the characterization allowed the most appropriate materials to be selected. Various composites presented acceptable general properties suggesting their suitability as substitutes for commercial materials in dentistry. PMID- 11193093 TI - Non-invasive determination of ethanol, propylene glycol and water in a multi component pharmaceutical oral liquid by direct measurement through amber plastic bottles using Fourier transform near-infrared spectroscopy. AB - Fourier transform near-infrared (FT-NIR) spectroscopy was used to quantify rapidly the ethanol (34-49% v/v), propylene glycol (20-35% v/v) and water (11-20% m/m) contents within a multi-component pharmaceutical oral liquid by measurement directly through the amber plastic bottle packaging. Spectra were collected in the range 7302-12,000 cm-1 and calibration models set-up using partial least squares regression (PLSR) and multiple linear regression. Reference values for the three components were measured using capillary gas chromatography (ethanol and propylene glycol) and Karl Fischer (water) assay procedures. The calibration and test sets consisted of production as well as laboratory batches that were made to extend the concentration ranges beyond the natural production variation. The PLSR models developed gave standard errors of prediction (SEP) of 1.1% v/v for ethanol, 0.9% v/v for propylene glycol and 0.3% m/m for water. For each component the calibration model was validated in terms of: linearity, repeatability, intermediate precision and robustness. All the methods produced statistically favourable outcomes. Ten production batches independent of the calibration and test sets were also challenged against the PLSR models, giving SEP values of 1.3% v/v (ethanol), 1.0% v/v (propylene glycol) and 0.2% m/m (water). NIR transmission spectroscopy allowed all three liquid constituents to be non-invasively measured in under 1 min. PMID- 11193094 TI - Chemiluminescence detection of nine corticosteroids in liver. AB - A method for the determination of nine corticosteroids in bovine liver was developed. The liquid-liquid extraction method consisted in the addition of sodium hydroxide to the tissue sample followed by extraction with ethyl acetate. After centrifugation, the extract was evaporated to dryness and the residue redissolved in acetonitrile. The removal of fats was performed with n-hexane and the acetonitrile layer was evaporated. Afterwards, analysis of the extracts was performed using high-performance liquid chromatography with chemiluminescence detection employing luminol as reagent. The recovery curves, performed at five spiking levels (different for each corticosteroid), showed that recoveries of at least 70.5% could be obtained from liver. The chemiluminescence detection gave satisfactory results with respect to sensitivity, and the LOQ ranged from 0.13 ppb for prednisolone to 8.40 ppb for betamethasone. The maximum mean RSD was 4.8% and 7.3% for intra- and inter-day assay, respectively. PMID- 11193096 TI - Bibliography. Current world literature. Nutrition and ageing. PMID- 11193095 TI - Normal and differential demasking flow-injection manifold for the direct spectrophotometric determination of zinc(II) in biological materials and pharmaceutical formulations. AB - A normal and a differential demasking flow-injection (FI) manifold were developed and optimized for the spectrophotometric determination of microamounts of Zn(II) in biological materials and pharmaceutical formulations. The reported method is very sensitive, rapid, simple and it is based upon the reaction of Zn(II) with 2,2'-dipyridyl-2-pyridylhydrazone (DPPH) in a strongly basic medium to form a yellow-coloured complex (lambda max = 448 nm). By using the differential demasking manifold, the tolerance of the method to many cations was enhanced by a mean factor of 25. The obtained calibration graphs were linear in the range of 0 10 mg l-1 Zn(II), at a sampling rate of 120 injections h-1 in both cases. The precisions of both manifolds were very good (RSD = 0.6 and 0.8%, respectively) and the 3 sigma detection limits were quite satisfactory (cL = 4 and 6 ng ml-1 respectively). The method has been successfully applied to the determination of Zn(II) in serum, human hair and pharmaceutical formulations with recoveries ranging between 98.0 and 101.6%. The obtained results were also in excellent agreement with flame atomic absorption spectrometry (FAAS), since the mean relative error was er = 0.9%. PMID- 11193097 TI - Bibliography. Current world literature. Protein metabolism. PMID- 11193098 TI - Inhibitory control of synaptic activity in goldfish Mb bipolar cell terminals visualized by FM1-43. AB - To investigate the physiology and plasticity of mixed rod-cone ON-bipolar cells (Mb) in the goldfish retina, we established a slice preparation which allows us to optically monitor the synaptic activity of bipolar cell axon terminals. We used the styryl dye FM1-43 which is incorporated into active axon terminals due to synaptic vesicle cycling and thus reflects synaptic activity. Different activity states of the axon terminals were revealed when slices prepared from light-adapted retinae were incubated in the presence of FM1-43 under various conditions. Depolarizing high K+ Ringer (50 mM) and the gamma-butyric acid (GABA) antagonist bicuculline (100 microM) resulted in more than two-fold increase in the number of stained terminals compared to slices stained in normal Ringer. In contrast, GABA treatment (0.5 mM) reduced the frequency of stained terminals. Thus, in light-adapted retinal slices the synaptic activity of Mb axon terminals can be modulated towards higher and lower activity states. The fact that the GABA antagonist bicuculline had similar effects as stimulatory high K+ Ringer suggests that inhibitory control is an important component in the regulation of synaptic activity and transmitter release in Mb terminals. PMID- 11193099 TI - Long-term maturation of visual pathways. AB - Previous research in adults has demonstrated the utility of the visual evoked potential (VEP) to measure the integrity of the chromatic and achromatic visual pathways. The VEP has also been shown to be a valuable indicator of maturation of these pathways in infants up to 1 year of age. The present manuscript reports changes in the visual pathways from 2 years to adulthood as measured by the spatio-chromatic VEP. The responses to achromatic reversal stimuli designed to preferentially activate the low spatial-frequency achromatic (luminance) pathways appear adult-like by 1 year of age. The responses to low spatial-frequency isoluminant onset stimuli designed to preferentially activate the chromatic pathway do not appear as they do in the adult until after 12-13 years of age. The shapes of the chromatic VEP waveforms shift from a positive-negative complex to a negative-positive complex. These changes can be modeled by a decrease in the latency of a large negative component between the ages of 1 year and adulthood. The results suggest that for low spatial-frequency stimuli, there are long-term changes in the development of the chromatic pathways that are not observed in the low spatial-frequency achromatic pathways. The changes in the chromatic VEP waveforms with age may be a physiological correlate of reported behavioral changes. PMID- 11193101 TI - Salamander rods and cones contain distinct transducin alpha subunits. AB - The mammalian retina is known to contain two distinct transducins that interact with their respective rod and cone pigments. However, there are no reports of a nonmammalian species having two distinct transducins. In the present study, we report the cloning and cellular localization of two transducin a subunits (G alpha t) from the tiger salamander. Through degenerate polymerase chain reaction (PCR) and subsequent screening of a salamander retina cDNA library, we have identified two forms of G alpha t. When compared to existing sequences in GenBank, the cloned subunits showed high similarity to rod and cone transducins. The salamander G alpha t-1 has 91.2-93.7% amino acid sequence identity to mammalian rod G alpha t subunits and 79.7-80.9% to mammalian cone Gats. The salamander G alpha t-2 has 86.2-87.9% sequence identity to mammalian cone G alpha ts and 78.9-80.9% to mammalian rod G alpha ts at the amino acid level. The G alpha t-1 cDNA encodes 350 amino acids while the G alpha t-2 cDNA encodes 354 residues, which is typical for rod and cone G alpha ts, respectively, and we thus identified the G alpha t- 1 as rod and G alpha t-2 as cone G alpha t. Sequences identified as effector binding sites and GTPase activity regions are highly conserved between the two subunits. Genomic Southern blot analysis showed that rod and cone G alpha t subunits are both encoded by single-copy genes. Northern blot analysis identified retina-specific transcripts of 3.0 kb for rod G alpha t and 2.6 kb for cone G alpha t. Immunohistochemistry in the flat-mounted salamander retina demonstrated that rod G alpha t is localized to rods, predominantly in the outer segments; similarly, cone G alpha t is localized to cone outer segments. The results confirm that the two sequences encode rod and cone transducins and demonstrate that this lower vertebrate contains two distinct transducins that are localized specifically to rod and cone photoreceptors. PMID- 11193100 TI - Functional dopamine deficits in the senile rat retina. AB - The activity of the endogenous retinal dopamine (DA) pathway has been examined in the pigmented rat using retinas obtained from normal adult (approximately 3 months) and senile adults (approximately 24 months) using an in vitro electrophysiological approach. By comparing the pharmacological sensitivity of the horizontal cells (HCs) to exogenous DA, a D1 receptor antagonist (SCH 23390) and a DA-transport inhibitor (nomifensine), it is suggested that there is a functional deficit in the endogenous DA activity in the senile retina. Cells recorded from retinae obtained from senile animals are more sensitive to exogenous DA, whilst the senile retina is insensitive to SCH 23390. In addition, nomifensine was effective in potentiating subthreshold DA applications, but only in the normal adult retina. The data may suggest that endogenous DA release upon the HCs and selective re-uptake are suppressed in these retinae. These functional deficits also appear to be associated with changes in the receptive fields of the HCs, suggesting there is a corresponding deficit in spatial processing at the outer plexiform layer (OPL) of the senile rat. PMID- 11193103 TI - Mathematical models for the spatial receptive-field organization of nonlagged X cells in dorsal lateral geniculate nucleus of cat. AB - Spatial receptive fields of relay cells in dorsal lateral geniculate nucleus (dLGN) have commonly been modeled as a difference of two Gaussian functions. We present alternative models for dLGN cells which take known physiological couplings between retina and dLGN and within dLGN into account. The models include excitatory input from a single retinal ganglion cell and feedforward inhibition via intrageniculate interneurons. Mathematical formulas describing the receptive field and response to circular spot stimuli are found both for models with a finite and an infinite number of ganglion-cell inputs to dLGN neurons. The advantage of these models compared to the common difference-of-Gaussians model is that they, in addition to providing mathematical descriptions of the receptive fields of dLGN neurons, also make explicit contributions from the geniculate circuit. Moreover, the model parameters have direct physiological relevance and can be manipulated and measured experimentally. The discrete model is applied to recently published data (Ruksenas et al., 2000) on response versus spot-diameter curves for dLGN cells and for the retinal input to the cell (S-potentials). The models are found to account well for the results for the X-cells in these experiments. Moreover, predictions from the discrete model regarding receptive field sizes of interneurons, the amount of center-surround antagonism for interneurons compared to relay cells, and distance between neighboring retinal ganglion cells providing input to interneurons, are all compatible with data available in the literature. PMID- 11193102 TI - Spatial summation and center-surround antagonism in the receptive field of single units in the dorsal lateral geniculate nucleus of cat: comparison with retinal input. AB - Spatial summation and degree of center-surround antagonism were examined in the receptive field of nonlagged cells in the dorsal lateral geniculate nucleus (dLGN). We recorded responses to stationary light or dark circular spots that were stepwise varied in width. The spots were centered on the receptive field. For a sample of nonlagged X-cells, we made simultaneous recordings of action potentials and S-potentials, and could thereby compare spatial summation in the dLGN cell and in the retinal input to the cell. Plots of response versus spot diameter showed that the response for a dLGN cell was consistently below the response in the retinal input at all spot sizes. There was a marked increase of antagonism at the retinogeniculate relay. The difference between the retinal input and dLGN cell response suggested that the direct retinal input to a relay cell is counteracted in dLGN by an inhibitory field that has an antagonistic center-surround organization. The inhibitory field seems to have the same center sign (ON- or OFF-center), but a wider receptive-field center than the direct retinal input to the relay cell. The broader center of the inhibitory field can explain the increased center-surround antagonism at the retinogeniculate relay. The ratio between the response of a dLGN cell and its retinal input (transfer ratio) varied with spot width. This variation did not necessarily reflect a nonlinearity at the retinogeniculate relay. Plots of dLGN cell response against retinal input were piecewise linear, suggesting that both excitatory and inhibitory transmission in dLGN are close to linear. The variation in transfer ratio could be explained by sustained suppression evoked by the background stimulation, because such suppression has relatively stronger effect on the response to a spot evoking weak response than to a spot evoking a strong response. A simple model for the spatial receptive-field organization of nonlagged X-cells, that is consistent with our findings, is presented. PMID- 11193104 TI - Cyclic AMP has no effect on the generation, recovery, or background adaptation of light responses in functionally intact rod outer segments: with implications about the function of phosducin. AB - In retinal rods, light exposure decreases the total outer segment content of both cGMP and cAMP by about 50%. The functional role of the light-evoked change in cAMP is not known. It is postulated to trigger changes in the phosphorylation state of phosducin, a phosphoprotein that is phosphorylated in the dark by cAMP dependent protein kinase (PKA) and dephosphorylated by basal phosphatase activity when PKA is inhibited by the light-evoked drop in cAMP. In biochemical studies, dephosphorylated phosducin binds to free beta gamma dimer of transducin (Tbeta gamma) and prevents the regeneration of heterotrimeric transducin by blocking the re-association of the beta gamma and alpha subunits. Phosducin's interaction with Tbeta gamma is blocked when it is phosphorylated on a single residue by PKA. To evaluate the effect of the light-evoked fall in cAMP, functionally intact isolated lizard rod outer segments were dialyzed in whole-cell voltage clamp with a standard internal solution and electrical light responses were recorded with and without adding cAMP to the dialysis solution. Since the total outer segment content of cAMP in darkness is approximately 5 microM, internal dialysis with solution containing a much higher concentration (100 microM) of cAMP (or 8-bromo cAMP) will overcome the effects of a light-evoked decrease in its concentration by keeping cAMP-dependent processes fully activated. Neither cyclic nucleotide had any influence on the generation, light sensitivity, recovery, or background adaptation of the flash response. These results also argue against the participation of phosducin in the sequence of events that are responsible for these aspects of rod function. This does not exclude the possibility of phosducin being involved in adaptation caused by higher light levels than used in the present study, that is, bleaching adaptation, or in light-dependent processes other than phototransduction. PMID- 11193105 TI - Distribution of terminals from pedunculopontine tegmental nucleus and synaptic organization in lateralis medialis-suprageniculate nucleus of cat's thalamus: anterograde tracing, immunohistochemical studies, and quantitative analysis. AB - The cat's lateralis medialis-suprageniculate nuclear complex (LM-Sg) in the thalamus receives input from various brain regions such as the superior colliculus, brain stem, and spinal cord, as well as from visual association cortex. In a previous study, we demonstrated that LM-Sg receives cholinergic fibers from the pedunculopontine tegmental nucleus (PPT) and that cholinergic terminals make synaptic contacts with the dendrites of glutamatergic projection neurons and of GABAergic interneurons (Hoshino et al., 1997). In this study, we investigate the distribution and the organization of PPT terminals by means of a combined anterograde tracer (biotinylated dextran amine, BDA) and immunohistochemical methods. When stained by acetylcholinesterase (AChE), the LM Sg is not uniformly immunoreactive, but rather is patchily labeled and shows a streaming type of reactivity. The tissue content appears high in enzyme activity in AChE-positive zones and is much lighter in activity in AChE-negative zones. We compared the synaptic organization between AChE-positive and AChE-negative portions of the LM-Sg in separate groups of electron-microscopic material: four types of vesicle containing profiles (RS, RL, F1, and PSD) as well as synaptic glomeruli were observed in this nucleus. Among these, the PSD profiles were observed more frequently in AChE-positive portions than in AChE-negative zones. Furthermore, the number of glomeruli was significantly higher in AChE-positive than in AChE-negative zones. Following the injection of BDA into PPT, labeled terminals within LM-Sg were rather more concentrated in the AChE-positive portion. Although the majority of PPT terminals made synaptic contacts with dendrites in the neuropil, a few terminals were involved in the synaptic glomeruli. The present results show that the synaptic organization is distinctly different between the AChE-positive and AChE-negative portions of LM-Sg. These results suggest that the AChE-positive portions of LM-Sg are relatively more involved in integrating information arising from a diverse set of inputs and processing that information within glomeruli in a complex manner than occurs in the AChE-negative portion of LM-Sg. PMID- 11193106 TI - The timecourse of neuronal connections of the rotundoectostriatal pathway in chicks (Gallus gallus) during embryogenesis: a retrograde transport study. AB - The avian retinotectofugal pathway has been suggested to be homologous to the mammalian retinotectofugal pathway. The projection of the nucleus rotundus upon the ectostriatum is equivalent to that of the pulvinar nucleus upon the extrastriate cortex in mammals. In this system, the optic tectum relays retinal input to the nucleus rotundus, which then ascends to the ectostriatum of the telencephalon. Given the fact that the chick retinotectofugal system becomes mature early during development, the present study attempted to investigate the timecourse of neuronal connections of the embryonic rotundoectostriatal pathway. We used multiple injections of cholera toxin B subunit (CTb) in the ectostriatum of chick embryos to retrogradely trace projections to the nucleus rotundus. We found CTb-labeled neurons in the nucleus rotundus at embryonic day 7.5-8. By embryonic day 8-8.5, increased numbers of CTb-labeled neurons were seen in the nucleus rotundus. It was noted that the time of this initial connection between the nucleus rotundus and the ectostriatum is nearly synchronous with that of the retinotectal and tectorotundal pathways, respectively (Crossland et al., 1975; Thanos & Bonhoeffer, 1987; Wu et al., 2000). These findings, combined with the present study, suggest that the retinotectofugal system becomes established, at least at a structural level, by embryonic day E8. PMID- 11193107 TI - Divergent mechanisms for phototransduction of invertebrate microvillar photoreceptors. AB - Recently, it was reported that the polyunsaturated fatty acids (PUFAs), arachidonic acid (AA) and linolenic acid (LNA), activate the light-sensitive channels in Drosophila photoreceptors (Chyb et al. 1999). We have examined whether these PUFAs activate the light-sensitive channels in Limulus ventral photoreceptors. We find that, whether applied from the outside or injected into a Limulus ventral photoreceptor, either AA or LNA fails to activate the light sensitive channels. Moreover, the synthetic diacylglycerol analog, 1-oleoyl-2 acetyl-sn-glycerol, also fails to activate the light-sensitive channels. We suggest that these findings require us to rethink our view about the generality of the process of phototransduction in invertebrate microvillar photoreceptors. We propose that the photoreceptors of Drosophila and Limulus evolved to utilize different branches of the phosphoinositide pathway for phototransduction: those of Limulus evolved to utilize IP3-mediated calcium release while those of Drosophila evolved to utilize diacylglycerol and it's downstream products. PMID- 11193108 TI - The feedforward component in depolarizing red responses of R/G horizontal cells in carp retina. AB - Light responses of R/G chromaticity-type horizontal cells (R/G HCs) and luminosity-type horizontal cells (LHCs) were intracellularly recorded in isolated superfused carp retina, and the response dynamics analyzed. The results revealed that (1) No significant difference in delay was detected between R/G HC red and green responses; (2) The rising speed was quicker for R/G HC depolarizing red responses compared to that of its hyperpolarizing green responses; and (3) Dynamic characteristics of R/G HC red responses and its changes caused by green background illumination did not follow that of LHC red response. All these results suggest that the depolarizing response of the R/G HCs cannot be entirely mediated by the negative feedback pathway from LHCs onto cones. A direct inhibitory input from red cones to R/G HCs may exist. PMID- 11193109 TI - GABA and GABA(A) receptor antagonists alter developing cone photoreceptor development in neonatal rabbit retina. AB - Gamma aminobutyric acid (GABA) has been established as an important developmental signal in a number of regions of the central nervous system (CNS), including retina. Our previous studies have shown that GABAergic horizontal cells act as the initial synaptic target for developing cone photoreceptors in neonatal rabbit retina. Since intraocular injections of the GABA(A) receptor antagonists, picrotoxin or bicuculline, disrupt cone synaptogenesis in vivo, GABA released from horizontal cells may provide a necessary signal for cone axon growth and/or synapse formation. In the current report, we have used cultured retinal explants to examine the effects of GABA(A) receptor antagonists on other aspects of developing cones. These include the distribution pattern of cone cell bodies across the outer surface of the retina and the expression of GABA(A) receptors within both cone cell bodies and axonal processes. Peanut agglutinin (PNA), a plant lectin that specifically labels cone plasma membrane and extracellular matrix, was used to monitor cone development, and a GABA(A) receptor antibody against the beta2/3 subunits of the protein was used to label GABA(A) receptors. Results showed that cones maintained in the explant culture express GABA(A) receptors in a temporal and spatial pattern similar to that observed in vivo, namely a low expression of receptors on cone cell bodies at postnatal day 1 (P1), peaking around P3 and diminishing by P7. Neonatal retinal explants exposed to the GABA(A) receptor antagonists, bicuculline (10 microM) or SR95531 (5 microM), for 24 h in culture showed disruption of the normal distribution of cone cell bodies. When GABA (100 microM) was added along with either antagonist, cone cell bodies appeared normal. Neither bicuculline nor SR95531 alone had any effect on the general morphology of other retinal layers, suggesting that these GABA(A) receptor antagonists at the concentrations used were not acting as nonspecific disruption agents. The effects of GABA antagonists were confined to the first week after birth with no disruption seen in P9 or adult explant cultures. These data provide a direct demonstration of the necessity for GABAergic input to cones during active synaptogenesis. As we have previously shown, GABA(A) receptor activation causes a substantial increase in intracellular calcium concentrations in cones and thereby could provide a mechanism by which GABA regulates cone maturation. PMID- 11193110 TI - Photoreceptor types and distributions in the retinae of insectivores. AB - The retinae of insectivores have been rarely studied, and their photoreceptor arrangements and expression patterns of visual pigments are largely unknown. We have determined the presence and distribution of cones in three species of shrews (common shrew Sorex araneus, greater white-toothed shrew Crocidura russula, dark forest shrew Crocidura poensis; Soricidae) and in the lesser hedgehog tenrec Echinops telfairi (Tenrecidae). Special cone types were identified and quantified in flattened whole retinae by antisera/antibodies recognizing the middle-to-long wavelength-sensitive (M/L-)cone opsin and the short-wavelength-sensitive (S-)cone opsin, respectively. A combination of immunocytochemistry with conventional histology was used to assess rod densities and cone/rod ratios. In all four species the rods dominate at densities of about 230,000-260,000/mm2. M/L- and S cones are present, comprising between 2% of the photoreceptors in the nocturnal Echinops telfairi and 13% in Sorex araneus that has equal diurnal and nocturnal activity phases. This suggests dichromatic color vision like in many other mammals. A striking feature in all four species are dramatically higher S-cone proportions in ventral than in dorsal retina (0.5% vs. 2.5-12% in Sorex, 5-15% vs. 30-45% in Crocidura poensis, 3-12% vs. 20-50% in Crocidura russula, 10-30% vs. 40-70% in Echinops). The functional and comparative aspects of these structural findings are discussed. PMID- 11193111 TI - Cortical area V4 is critical for certain texture discriminations, but this effect is not dependent on attention. AB - This study examined the question of which features of a complex grouping discrimination make it vulnerable to permanent elimination by V4 lesions. We first verified that the line element grouping discrimination, which we previously reported to be devastated by V4 lesions, was similarly affected in the monkeys of this study. The permanence of the deficit was established by mapping its visual field distribution and then testing this discrimination for an extended period at a locus on the border of the deficit. Also, a staircase procedure was used to provide the monkey with within session instruction in the grouping discrimination, but this did not improve V4 lesion performance. Grouping was then compared with several discriminations that shared some features with it, but which were found not to be permanently eliminated by V4 lesions. This comparison suggested that grouping (rather than segmentation or response to a single element) was one feature that made the discrimination vulnerable, a second was the similarity in shape of the texture elements to be grouped. Finally, we tested visual crowding, a property of peripheral vision that is thought to reflect neuronal interactions early in visual cortex, possibly in area V1, and found no effect of V4 lesions. A control experiment with human observers tested whether the elimination of grouping by V4 lesions might be due to an alteration of attention, but found no evidence to support this hypothesis. These results show that severe disruption of texture discriminations by V4 lesions depends on both the nature of the discrimination and the type of texture elements involved, but does not necessarily involve the disruption of attention. PMID- 11193112 TI - Two-frequency analysis of interactions elicited by Vernier stimuli. AB - In five subjects, we measured visual evoked potentials (VEPs) elicited by Vernier targets in which the contrast of the two components of the stimuli were modulated by sinusoids at distinct frequencies fl and f2. This approach allows for the extraction of VEP signatures of spatial interactions, namely, responses at intermodulation frequencies n1f1 + n2f2, without the need to introduce motion into the stimulus. The most prominent interactions were at the sum frequency f1 + f2, and, for frequency pairs that were sufficiently separated, the difference frequency f1- f2. These responses had a systematic dependence on the temporal parameters of the stimulus, corresponding to an effective latency of 145 to 165 ms. Fourth-order interactions were also detected, particularly at the frequencies 2f1 +/- 2f2. These VEP signatures of interaction were similar to interactions seen for colinear line segments separated by a gap. Thus, for Vernier stimuli devoid of motion, VEP signatures of interaction are readily detected but are not specific to hyperacuity displacements. The distribution of interactions across harmonic orders is consistent with local rectification preceding the spatial interactions. Their effective latencies and dependence on spatial parameters are consistent with interactions within V1 receptive fields or mediated by horizontal connections between cells with a similar orientation tuning within V1. PMID- 11193113 TI - Supracondylar fractures of the humerus in children--back to basics. PMID- 11193114 TI - The Internet: another facet to the paradigm shift in healthcare. AB - The Internet is an extremely powerful innovation that has and will continue to shape the healthcare industry in the years to come. Albeit a little too slowly, doctors are starting to catch onto this new wave of digital empowerment and creating niches that will enhance their ability to care for their patients and ultimately add value to their practices. The challenge is to encourage every doctor to come on board. The paradigm shift in healthcare delivery is that the Internet brings about the power of information to the patient. This balances the power in the doctor patient relationship. Taken positively, the doctor too can benefit from Internet technology. The biggest contribution of the Internet in the area of electronic medical records is the web-based display environment that is operating-system independent. The Internet can therefore be exploited to provide a supra system that can draw personal medical information together from anywhere to create a virtual electronic medical record. The Internet can also be used to shape up an Internet-based healthcare delivery system. The healthcare delivery paradigm shift brought about by the Internet calls for an eHealth strategy. PMID- 11193115 TI - Profile of a menopause clinic in an urban population in Malaysia. AB - The object of this study is to determine the status of an urban Malaysian woman in her menopause age group with reference to her menopausal symptoms, lipid profile, breast, pelvis and bone. One hundred and sixty four women attending the Menopause Clinic of University Hospital, Kuala Lumpur who had not previously been on hormone replacement therapy were studied. Forty nine women were perimenopausal, 74 women were in early menopause (within 5 years of menopause) and 41 women were in late menopause (after 5 years of menopause). The most common symptoms were hot flushes (56%) and generalised tiredness (49%). Eighty four percent (84%) of women had high cholesterol levels. Serum triglycerides were highest in the late menopause group. There were 2 cases of intraductal carcinoma diagnosed on routine mammography, with 8 cases of fibrocystic breast disease and 7 cases of suspicious breast lumps. Routine ultrasound (pelvic and abdominal) revealed two women with ovarian cysts, 6 women with an endometrial thickness of more than 5 mm and 8 women with uterine fibroids. Eighty five women (51.8%) had mild osteoporosis while four women had moderate osteoporosis on dual photon measurements for bone mineral density. Menopause clinics should aim at investigating a woman in her menopause as a whole. Vasomotor symptoms were common in the urban Malaysian menopausal woman. There was a high incidence of lipid abnormalities. Routine mammography, pelvic ultrasound examinations and bone mineral density tests detected significant pathology and abnormalities. PMID- 11193116 TI - Gradual reduction of supracondylar fracture of the humerus in children reporting late with a swollen elbow. AB - AIM: To study the outcome of gradual reduction by skin traction of supracondylar fracture of the humerus in children with swollen elbow, who seek treatment two days or longer after the injury. METHOD: Fifteen children aged between 4 and 11 years (average 7 years 11 months), who had initially consulted a traditional practitioner, reported between 2 and 21 days (average 7.5) after the injury were treated by skin traction with the elbow kept straight and the forearm in position of comfort. RESULTS: The average duration of stay in hospital was 14 days. All fractures healed; there was no incidence of myositis ossificans or neurovascular deficit. All patients had functional range of movements at the elbow within 6 months. Five patients developed cubitus varus deformity greater than 5 degrees, they were classified as poor result. Four out of these 5 patients had sought treatment after a delay of 7 days or longer. There were 9 good (60%), 1 fair (7%) and 5 poor (33%) results. CONCLUSION: Gradual reduction by skin traction is safe. It is possible to achieve satisfactory reduction if the delay is up to 7 days. The results with regards to deformity and function were comparable with those obtained following open or closed Kirschner wire fixation. PMID- 11193117 TI - Squamous cell carcinoma of the temporal bone: diagnosis, treatment and prognosis. AB - Squamous cell carcinoma of the external ear canal is an uncommon condition that is associated with a poor outcome. The development of an accepted staging system has not been forthcoming and this has inhibited the formation of an evidence based therapeutic protocol. We report the findings in 14 patients with squamous cell carcinoma of the external ear canal treated in our institutions. The most common presenting symptoms were otorrhoea and otalgia. Four patients had a history of chronic ear discharge and one had previous radiotherapy for nasopharyngeal carcinoma. Five patients had facial palsy which was a poor prognostic sign. Only one patient had clinical neck disease. Pre-operative imaging with CT or MRI scans was accurate in determining the extent of tumour involvement. The initial T-staging relied heavily on these findings. With combination treatment involving surgery, radiotherapy and chemotherapy, disease free survival achieved was 69% (9 of 13) over a mean follow-up period of 24.7 months. One patient absconded treatment. Patients with early stage tumours faired better than patients with advanced tumours (100% vs 33%). There was low incidence of involvement of the parotid gland (1 of 7 patients). Patients with facial nerve involvement had a significantly poorer outcome (p = 0.035). PMID- 11193118 TI - Results of fixation of clavicle alone in managing floating shoulder. AB - AIM OF STUDY: A retrospective review on the outcomes of four floating shoulder, ipsilateral scapular neck and clavicular fractures, treated with open reduction and internal fixation of the clavicle alone using plate and screws. METHODS: All patients were evaluated by interview, physical examination and radiological examination at an average follow up period of 3.3 years (range: 2-4 years). Functional outcomes were rated using Rowe's score. RESULTS: Radiological union of both fractures occurred at an average of 2.8 months (range: 8-12 weeks). Excellent result was seen in three cases and good in one. CONCLUSION: Plating of clavicle alone restored stability of shoulder and allowed early range of motion exercises. All cases gained good and excellent function. PMID- 11193119 TI - Abdominal pregnancy: a case report and literature review. AB - We report a rare and unusual case of an Abdominal pregnancy that was delivered successfully at term. It is the first documented case in the local literature in almost 30 years. What makes it even more exceptional is that despite the high mortality associated with the condition, both mother and baby survived the ordeal. She subsequently delivered another child, 2 years later by an elective lower segment caesarean section and had a tubal ligation performed concomitantly. A review of the topic and its management is also presented. PMID- 11193120 TI - Aberrant regeneration of the third nerve. AB - We describe three patients with aberrant regeneration of the third nerve secondary to traumatic brain injury. The full blown features of the syndrome include horizontal gaze-eyelid synkinesis, pseudo-Graefe sign, limitation of elevation and depression of the eye with retraction of the globe on attempted vertical movements, adduction of the involved eye on attempted elevation or depression, pseudo-Argyll Robertson pupil and absent vertical optokinetic response. The 'misdirection' incidence in our study is 15%. PMID- 11193121 TI - Successful repair of traumatic aortic tears using left heart bypass. AB - Aortic tears commonly occur in multiply injured patients. Recognizing this injury is important. A chest X-ray is helpful and a CT-angiogram or aortogram confirmatory. After attending to life-threatening injuries, the aortic tear should be repaired immediately. Using the left heart bypass technique has the lowest risk of operative neurologic injury. We review our experience over the last 2 years, discuss our preferred technique and report on the outcome. PMID- 11193122 TI - Meningioma with rhabdoid transformation. AB - A 29-year-old man was operated on for an intracranial tumour with the gross features of a meningioma. Histology showed features of a rhabdoid tumour. The tumour recurred in 1997, 17 months after the first operation, and was re-excised and showed identical histology. Meningiomas with rhabdoid change are very rare. The clinicopathologic features are presented and the differential diagnoses discussed. PMID- 11193123 TI - Percutaneous interventional strategies in the treatment of chronic total coronary occlusions. AB - Chronic total coronary occlusions which make up 10% to 20% of all interventional procedures in high-volume centres remain a vexing problem for invasive cardiologists for 2 main reasons. First, they are only successfully recanalised in about 60% of attempts with most failures resulting from an inability to cross the lesions. Laser guidewire appears to be a promising innovation in overcoming this obstacle. Second, after initially successful recanalisation with conventional balloon angioplasty (PTCA), a high restenosis rate (range, 45% to 75%) is observed. Stent placement, by conferring maximal luminal expansion, appears to have resolved this problem to a large extent; both observational and randomised studies indicate that after stent placement, restenosis rate is at least halved that of PTCA. PMID- 11193124 TI - Clinics in diagnostic imaging (53). Hepatic portal venous gas due to mesenteric infarction. AB - A 43-year-old woman presented with acute abdominal pain and signs of ileus. CT scan of the abdomen showed hepatic portal venous gas. At surgery, a long segment of gangrenous bowel extending from the jejunum to the proximal hemicolon was found. The cause was superior mesenteric artery occlusion. The aetiology, imaging features and clinical significance of hepatic portal venous gas are discussed. PMID- 11193125 TI - Postmenopausal hormone replacement therapy and hypertension. PMID- 11193126 TI - Hormone replacement therapy and hypertension. AB - For many years, Hormone Replacement Therapy (HRT) was considered to be contraindicated in postmenopausal women with hypertension and many such women were excluded from HRT because of concerns that HRT may have an adverse effect on blood pressure. This perception was mainly due to the effects of oral contraceptive drugs, especially the oestrogen component, in increasing blood pressure. Differences exist between the formulation and doses of oestrogen preparations used, either as oral contraceptives in premenopausal women (in whom high-dose synthetic oestrogens are used) or as HRT in postmenopausal women (in whom low "replacement" doses of natural oestrogens are used). This is not inconsequential, as postmenopausal women represent the largest category of women at risk for hypertension. The aim of this review is to give a balanced view on the effects of HRT on blood pressure in postmenopausal women. PMID- 11193127 TI - Association analysis of two tyrosine hydroxylase gene polymorphisms in normotensive offspring from hypertensive families. AB - OBJECTIVE: We have studied possible association between predisposition to essential hypertension, plasma noradrenaline level and two polymorphisms of the gene for tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine biosynthesis. DESIGN AND METHODS: One hundred and one normotensive sons from normotensive parents (SN) and 107 normotensive sons of hypertensive families (SH) were studied. Tetranucleotide TCAT repeat and Va181Met polymorphisms of the TH gene were determined by polymerase chain reaction (PCR) technique. RESULTS: SH had higher systolic BP and plasma noradrenaline concentration than the SN group. No significant difference was found between the allele and genotype frequencies in the SH and SN groups for both polymorphisms. The two polymorphisms were in tight linkage disequilibrium. The CD genotype of the microsatellite marker was associated with increased plasma noradrenaline concentration in both groups. Genotypes AB, AE and BB of the TCAT repeat polymorphism and genotypes VM and MM of the Va181Met polymorphism exhibited the greatest difference in plasma noradrenaline concentration between the SH and SN groups. CONCLUSION: The studied TH polymorphisms do not appear to be associated with family history of essential hypertension. Nevertheless, some genotypes of TH might be related to disturbance of plasma noradrenaline concentration. PMID- 11193128 TI - "To better know hypertension": educational meetings for hypertensive patients. AB - BACKGROUND: Pilot educational meetings were conducted to (1) verify the support of hypertensive patients in this initiative; (2) test the knowledge of patients regularly followed-up in our Hypertension Centre Outpatient Clinic concerning problems related to hypertension; (3) improve patients knowledge about hypertension through a formal teaching session, (4) compare the knowledge of these patients with that of a control group. METHODS: An invitation to participate in an educational program on hypertension was extended to 210 consecutive patients (group I ) followed-up in the outpatient clinic of our Hypertension Centre. Each meeting included four sessions: (1) an interactive phase with electronic devices aimed at evaluating the degree of information about hypertension by means of multiple-choice questionnaires, (2) a traditional teaching session, (3) an interactive phase to assess the compliance to treatment, and (4) a general discussion session. The control group (II) included 144 hypertensive patients referred for the first time to our Hypertension Centre. Before the initial visit the patients were asked to answer a questionnaire identical to that provided to group I during the meetings. RESULTS: The meetings were attended by 183 out of the 210 patients in group I (participation rate = 87%). The answers to the questions were corrected as a percentage ranging from 73.7 to 95.6 in group I and from 43.9 to 74.7 in group II (p < 0.01). The provision of more detailed information about problems in hypertension was associated with better compliance to treatment and blood pressure control. (BP under treatment 138 +/- 14/83 +/- 7 mmHg in group I, 152 +/- 15/91 +/- 11 mmHg in group II; (p < 0.01). CONCLUSIONS: Our data indicate that this type of educational approach is appreciated by patients (participation rate 87%) and that the level of knowledge about hypertension and compliance to treatment are greater in selected patients than in control patients. PMID- 11193129 TI - Pulse pressure: a predictor of cardiovascular mortality among young normotensive subjects. AB - Wide pulse pressure has been associated with increased cardiovascular disease events among hypertensive subjects. To test the hypothesis that this association also exists among normotensive subjects, data from the first National Health and Nutritional Examination Survey and the 1992 Epidemiological Follow-up Study were analyzed. The study group included 7346 participants, aged 25-74 years, with baseline blood pressure levels <140/90 mmHg and without a history of hypertension. Deaths from cardiovascular disease and all other causes were determined. At entry, mean age and blood pressure level were 43.4 years and 118/76 mmHg. During an average follow-up period of 17.4 years, there were 1443 (19.6%) deaths, 557 of them ascribed to cardiovascular disease. Age-race-adjusted cardiovascular mortality was significantly higher for those in the highest quartile of pulse pressure (> or = 50 mmHg). However, after stratification into age <55 years and > or = 55 years, and controlling for other cardiovascular risk factors, increased pulse pressure was associated with cardiovascular mortality only in younger men and women. In these subjects, men and women with pulse pressures > or = 48, and > or = 46 mmHg, respectively, had a relative risk (95% confidence in terval) of 2.35 (1.21-4.38) and 2.90 (1.34-4.98) for cardiovascular mortality with those with pulse pressures of less than 36 and 34 mmHg, respectively (p < 0.05) as reference. While systolic blood pressure by itself was a weaker predictor of cardiovascular mortality than pulse pressure, diastolic and mean arterial pressure were not predictive at all. No measure of blood pressure was related to mortality in those aged > or = 55 years. In conclusion, among young subjects, but not older normotensive persons, at very low risk of cardiovascular disease, a wide pulse pressure is associated with increased cardiovascular mortality. PMID- 11193130 TI - Substituting lifestyle management for pharmacological control of blood pressure: a pilot study in Australian general practice. AB - The HEART project was conducted in general practice to determine whether lifestyle strategies, aimed at increasing physical activity and dietary modification, can be substituted for drug therapy in patients who have been well controlled on antihypertensive medication. In addition to blood pressure (BP) and risk factor outcomes, lifestyle behaviours, quality of life of patients, and the acceptability of the approach to both general practitioners (GPs) and patients involved in the trial were assessed. Patients (n = 45) with a history of hypertension and who had been well controlled for at least the past 6 months (BP < 160/ 95 mmHg) were randomised to a continued medication (C) group (n = 24) or a withdrawal (W) group (n = 21). Subjects had received antihypertensive therapy for an average of 7.8 years (range 1-28 years). Drug therapy in the W group was recommenced if BP exceeded 160/95 mmHg on two consecutive visits. Both groups were counselled regarding lifestyle behaviour change by their GP throughout the study and were provided with specifically developed self-help materials. Subjects were reviewed at least monthly over a 9-month period. Following randomisation, there were no significant differences between the two groups for BP, heart rate, age, duration of therapy, total cholesterol or body mass index. All but three subjects (one from the W and two from the C group) completed 9 months of monitoring following randomisation and there were no cardiovascular events; 71% of subjects remained off drug therapy and were well controlled at the 9-month follow-up (15/21) with mean BP of 141/85 mmHg (W) and 139/ 86 mmHg (C). Systolic BP tended to increase during the study period in both W and C groups, however, no significant differences were observed in mean systolic or diastolic BP either between the two groups or within each group in comparison to baseline values. Resting heart rate, body mass index and cholesterol levels remained unchanged in both W and C groups after 9 months follow-up. There were no changes attributable to the lifestyle intervention in the subjects continuing drug therapy in BP or lifestyle variables over the study period. However, the group stopping therapy had a 6% reduction in body mass index after 9 months. These data suggest that a proportion of motivated patients willing to trial a lifestyle approach can cease drug therapy and be adequately maintained by the prescription of lifestyle advice via their GP for at least a 9-month period. Cessation of drug therapy may be an important motivating factor to achieve weight loss in this group. PMID- 11193131 TI - Dose response effect of conjugated equine oestrogen on blood pressure in postmenopausal women with hypertension. AB - OBJECTIVE: This study was designed to compare with placebo the dose-response of conjugated equine oestrogen (CEE) on blood pressure in hypertensive postmenopausal women. DESIGN AND METHODS: Fourteen postmenopausal women with grade 1-2 hypertension participated in the study which used a double-blind crossover design. There were four randomised treatment phases, each lasting 4 weeks. The four treatments were CEE 0.3 mg, CEE 0.625 mg, CEE 1.25 mg and placebo. Each subject also received non-blinded medroxyprogesterone acetate (MPA) 10 mg for the final 14 days of each 28-day treatment cycle. Clinic blood pressure was measured weekly with the mean values of weeks 3 and 4 of each phase used for analysis. Ambulatory blood pressure was performed in week 4 of each phase. RESULTS: Compared with placebo, clinic systolic blood pressure was reduced in the CEE 0.3 mg and CEE 0.625 mg phases (p < 0.05) and clinic diastolic blood pressure was reduced in the CEE 0.625 mg phase (p < 0.05). There was no significant effect of CEE on ambulatory blood pressure, although the blood pressure pattern was similar to clinic measurements. CONCLUSION: In hypertensive postmenopausal women, daily CEE together with cyclical MPA has a variable effect on blood pressure depending on CEE dose. The "lower" and "middle" doses of CEE produced a small reduction in blood pressure which reached a nadir and tended to reverse with the "higher" CEE dose. PMID- 11193132 TI - Comparison between isosorbide dinitrate in aerosol and in tablet form for the treatment of hypertensive emergencies in the elderly. AB - BACKGROUND: Isosorbide dinitrate in spray form is an effective and safe option for the treatment of hypertensive emergencies. The aim of this study was to evaluate whether isosorbide dinitrate spray is as effective and safe as treatment in tablet form for the management of hypertensive emergencies in the elderly. METHODS: Forty patients with hypertensive emergencies were randomly divided into two groups of 20 patients each. Group A received 1.25 mg isosorbide dinitrate aerosol upon arrival and a second dose 15 min later when mean systemic arterial pressure (MAP) reduction was <15% . Group B patients received a single 5 mg tablet of sublingual isosorbide dinitrate. RESULTS: Blood pressure in Group A patients decreased from 193 +/- 13/123 +/- 6.6 mmHg to 154 +/- 15/92.5 +/- 7.6 mmHg (p < 0.005), the reduction beginning 10 min after drug administration; no adverse effects were found. Two patients in Group B did not respond but for the other patients in this group blood pressure decreased from 197 +/- 10/121 +/- 7 to 154 +/- 11/90 +/- 4 mmHg, (p < 0.005), the reduction beginning 45 min after receiving the medication; 8 patients suffered headache. CONCLUSION: Our results indicate that isosorbide dinitrate aerosol is more effective than tablets for the treatment of elderly patients with hypertensive emergencies. PMID- 11193133 TI - Divergent effects of different beta-blocking agents on endothelium-dependent vasodilatation in the human forearm. AB - OBJECTIVE: The aim of this study was to evaluate the direct effect of three principally different beta-receptor blocking agents on endothelium-dependent vasodilatation (EDV) in the human forearm. METHODS: In 27 young normotensive subjects forearm blood flow (FBF) was measured with venous occlusion plethysmography during local intra-arterial infusions of methacholine (MCh), evaluating EDV, and sodium nitroprusside (SNP), evaluating endothelium independent vasodilatation (EIDV). The measurements of EDV and EIDV were undertaken at baseline conditions and repeated after 1 h of concomitant intra arterial infusion of atenolol (n = 8, 1.2 mg/h), propranolol (n = 7, 1.2 mg/h), labetalol (n = 7, 16 mg/h) or saline (n = 5). RESULTS: The selective beta-blocker atenolol showed a tendency to improve the FBF response to MCh (from 28.8 +/- 9.2 to 32.6 +/- 8.7 ml/min/ml tissue, p < 0.05). The nonselective beta-blocker propranolol attenuated the FBF response to MCh significantly (from 30.5 +/- 6.7 to 22.8 +/- 4.5 ml/min/ml tissue, p < 0.01). In these groups baseline FBF and EIDV were unchanged. Labetalol, a combined non-selective beta-blocker and selective alpha-1-blocker, increased baseline FBF and increased the response to both MCh and SNP in parallel (p < 0.05 for MCh and p = 0.07 for SNP). Saline did not change baseline FBF, EDV or EIDV. CONCLUSIONS: This study showed that local infusion of different beta-blocking agents in normotensive subjects affects endothelial vasodilatory function differently. This technique could be used to evaluate the direct effect of vasoactive drugs on EDV. PMID- 11193134 TI - Blood pressure control in essential hypertension and impairment of renal function with age. AB - Hypertension has been recognized to be an important cause for the development of end-stage renal disease (ESRD). We assessed the quality of blood pressure control in 103 patients with essential hypertension and correlated renal function and age. Patients were stratified into three subgroups by their blood pressure level under current medication. Group 1 were hypertensive patients with normalized blood pressure (<140/90 mmHg, n = 25), group 2 patients with mild hypertension (140-159/90-99 mmHg, n = 43) and group 3 patients with moderate to severe hypertension (> 160/100 mmHg, n = 35). A negative correlation between age and creatinine clearance (Ccr) could be confirmed for patients of group 1 (correlation coefficient r1 = -0.56; p, < 0.01) and group 2 (r2 = -0.55; P2 < 0.001). Furthermore the regression coefficient (m) of decline in C(Cr) versus age was higher in group 2 patients (m2 = -1.83) than in group 1 (m1 = -1.30). In group 3 we found no correlation of renal function with age, indicating that age may not be the leading variable. Patients in group 1 were all within normal limits of age adjusted Ccr, but 12% in group 2 and 23% in group 3 had impaired C(Cr). Furthermore proteinuria was found to be 20% (group 1), 26% (group 2) and 31% (group 3). This analysis provides further evidence of the importance of blood pressure control in essential hypertension to preserve renal function. PMID- 11193135 TI - L-arginine partially reverses established adrenocorticotrophin-induced hypertension and nitric oxide deficiency in the rat. AB - BACKGROUND: L-arginine treatment prevents adrenocorticotrophin (ACTH) induced hypertension in the rat. This study examined whether L-arginine treatment could reverse established ACTH hypertension and its effects on markers of decreased NO activity. METHODS: Sixty-four male Sprague-Dawley rats were randomly divided into 6 groups given 12 days of treatment: (1) sham (0.9% NaCl, 0.5 ml/kg, subcutaneously, sc, n = 16); (2) ACTH (0.5 mg/kg/day, sc, n = 16); (3) sham + L arginine (0.6% in food, from treatment day 8 onwards, n = 10); (4) ACTH + L arginine (n = 10); (5) sham + D-arginine (0.6% in food, from T 8 onwards) (n = 6); and (6) ACTH + D-arginine (n = 6). Systolic blood pressure, water intake, urine volume, and body weight were measured every second day. At the end of the experiments, plasma and urinary nitrate/nitrite (NOx), plasma amino acid concentrations (in groups 1-4), and urinary cyclic guanosine monophosphate (cGMP) concentrations were measured. RESULTS: Sham, sham + L-arginine, and sham + D arginine treatments did not affect blood pressure. ACTH increased systolic blood pressure (from 121 +/- 1 to 147 +/- 2 mmHg, p < 0.001, pooled control vs treatment day 12, mean +/- sem), and this was partially reversed by L-arginine (group 4: from 141 +/- 2 on day 8 to 133 +/- 1 mmHg on day 12, n = 10, p < 0.001). In contrast, D-arginine did not affect blood pressure in ACTH-treated rats (group 6). ACTH increased water intake and urine volume and decreased body weight, and L-arginine administration did not alter these parameters. ACTH decreased plasma citrulline (group 1 vs 2: 115 +/- 7 vs 67 +/- 6 micro M/L, n = 16, p < 0.001) and NOx concentrations (group 1 vs 2: 8.3 +/- 0.8 vs 4.5 +/- 0.6 microM/L, n= 10, p < 0.001) and these decreases were reversed by L-arginine treatment (group 4: citrulline 98 +/- 9 micro M/L, NOx 9.1 +/- 1.6 micro M/L, group 2 vs 4, both p < 0.05). ACTH produced marked increases in urinary cGMP excretion (group 1 vs 2: 0.5 +/- 0.1 vs 1.9 +/- 0.4 nmol/24 h, p < 0.01). CONCLUSION: Supplementation with L-arginine partly reversed established ACTH induced hypertension and restored plasma NOx and citrulline concentrations to levels seen in sham-treated rats. These data are consistent with previous studies suggesting that functional NO deficiency has a role in ACTH-induced hypertension in rats. PMID- 11193136 TI - Clinical Lewy body syndromes. AB - Lewy bodies are spherical, intracytoplasmic, eosinophilic, neuronal inclusions comprising abnormally truncated and phosphorylated intermediate neurofilament proteins, alpha-synuclein, ubiquitin, and associated enzymes. The clinical presentation of LB disease varies according to the site of LB formation and associated neuronal loss. Three main clinicopathological syndromes have been described--movement disorder, autonomic failure, and dementia. Parkinsonism is the most common presentation of LB disease developing in middle life. In older patients, a mixture of cognitive, autonomic, and motor dysfunction is more common. Dementia with LB (DLB) is a relatively recently described clinicopathological syndrome that accounts for up to 20% of all cases of dementia in old age. Patients, typically in their seventh and eighth decades, have LB pathology in cortical neurons as well as in the brain stem. LB disease should be considered in the differential diagnosis of a wide range of clinical presentations including episodic disturbances of consciousness, syncope, sleep disorders, and unexplained delirium. PMID- 11193137 TI - High frequency of mutations in four different disease genes in early-onset dementia. AB - Heterozygous mutations in the genes for amyloid precursor protein (APP), the presenilins (PS1, PS2), prion protein (PrP), neuroserpin, and tau are associated with early-onset dementia (EOD) with or without neurological signs in the early disease stage. To investigate the proportion of EOD without early neurological signs attributable to known genes we prospectively (i.e., ante mortem) screened these six genes for mutations in 36 patients with EOD before age 60. Family history for dementia was positive (PFH) in 16, negative (NFH) in 17, and unknown (UFH) in 3 patients. In 12 patients, we found 5 novel mutations (PS1: F105L; PS2: T122P, M239I; PrP: Q160X, T188K) and 5 previously reported mutations (APP: in three most likely unrelated patients V717I; PS1: A79V, M139V; PrP: P102L, T183A) that all are considered disease causing. Of these 12 patients, 9 had PFH. This indicates a detection rate of 56% (9/16) in patients with PFH. We found 2 mutations (APP V717I) in 2 of the 3 the UFH-patients, and only 1 mutation (PrP T188K) in 1 of the 17 patients with NFH. No mutation was found in tau and neuroserpin genes. To date, three patients died and FAD, predicted by PS mutations in two patients, and prion disease, predicted by a PrP mutation in the third one, were histopathologically confirmed at autopsy. Up to now, mutation findings may be the most specific biomarkers for an ante mortem diagnosis of FAD or hereditary prion disease. PMID- 11193138 TI - Pathological tau phenotypes. The weight of mutations, polymorphisms, and differential neuronal vulnerabilities. AB - In tauopathies, comparative biochemistry of tau aggregates shows that they differ in both phosphorylation and content of tau isoforms. Six tau isoforms are found in human brain that contain either three (3R) or four microtubule-binding domains (4R). In Alzheimer's disease, all six of the tau isoforms are phosphorylated and aggregate into paired helical filaments. They are detected by immunoblotting as a major tau triplet (tau 55, 64, and 69). In corticobasal degeneration and progressive supranuclear palsy, only phosphorylated 4R-tau isoforms aggregate and appear as a major tau doublet (tau 64 and 69). In Pick's disease, only phosphorylated 3R-tau isoforms aggregate into filaments and are characterized by another major tau doublet (tau 55 and 64). Finally, recent findings provide a direct link between a genetic defect in tau and its abnormal aggregation into filaments in frontotemporal dementia with parkinsonism linked to chromosome 17. In the present study, the question of a relationship between tau isoforms and cell morphology is raised. To answer this question, stably transfected human neuroblastoma SY5Y cell lines with either 3R- or 4R-tau isoforms are established. Cell morphology and tau phosphorylation were modified, suggesting that cells undergo profound changes in their metabolism and viability. PMID- 11193139 TI - Coexistent tau and amyloid pathology in hereditary frontotemporal dementia with tau mutations. AB - Hereditary frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) is associated with different mutations in the microtubule-associated protein (MAP) tau gene. Pathological changes consist of accumulation of hyperphosphorylated tau protein in frontal and temporal cortex, hippocampus, and some subcortical nuclei. We describe the neuropathological findings in five patients with P301L mutation, and in two affected sibs with R406W mutation. The P301L brains all showed a pretangle-type tauopathy of the frontal and temporal cortices. One of these patients, however, also showed an Alzheimer-type tauopathy with neurofibrillary tangles (NFT), neuritic plaques, and amyloid angiopathy of the temporoparietal cortex. Three tau bands (64, 68, and 72 kDa) were seen in the frontal cortex, while the temporal cortex revealed four bands (60, 64, 68, and 72 kDa), containing all six tau isoforms. The first R406W brain showed many NFT in affected regions with only a few diffuse amyloid plaques. The second R406W brain contained a much higher density of NFT in affected regions, and an extensive amyloid deposition consisting of both diffuse and neuritic plaques with dense cores. An intriguing question is whether the FTD and Alzheimer disease changes are concomitant, or whether there is an interaction between tau and amyloid pathology. An acceleration of NFT formation due to amyloid deposition has been observed in nondemented aging and preclinical AD. The question whether this mechanism occurs in FTD with tau mutations remains to be elucidated. PMID- 11193140 TI - The clinical spectrum of Guam ALS and Parkinson-dementia complex: 1997-1999. PMID- 11193141 TI - In vivo analysis of wild-type and FTDP-17 tau transgenic mice. AB - Mutations in the coding and intronic regions of the tau gene cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Some of these mutations lead to an overproduction of tau isoforms with four microtubule-binding repeats, followed by the development of fibrillary lesions and selective cell death. In order to analyze the development of these neurofibrillary lesions in transgenic mice, the longest four-repeat human brain tau isoform was expressed under control of two different neuron-specific promoters. In a first model, utilizing the human Thy1 promoter, transgenic tau was hyperphosphorylated and abnormally localized to cell bodies and dendrites. In a second model, which made use of a human Thy1.2 expression vector, transgenic expression levels were much higher, and an additional phenotype was observed: Large numbers of pathologically enlarged axons containing neurofilament- and tau-immunoreactive spheroids were present, especially in spinal cord. Signs of Wallerian degeneration and neurogenic muscle atrophy were observed. Behaviorally, transgenic mice showed signs of muscle weakness. Our data show that overexpression of human four-repeat tau in itself is sufficient to lead to nerve cell dysfunction and amyotrophy. We have now extended our initial studies by introducing exonic mutations including G2t 2V and PS01L into the tau gene in order to achieve a more advanced FTDP-17 associated phenotype. PMID- 11193142 TI - Pathogenic mechanisms of Alzheimer's disease analyzed in the APP23 transgenic mouse model. AB - APP23 transgenic mice overexpress human APP with the Swedish double mutation. The mice start to develop amyloid plaque pathology at about six months of age, followed somewhat later by vascular amyloid deposits. Plaques are mostly of the compact type and increase exponentially during aging. Female mice show a slightly more rapid A beta plaque deposition than do male animals. Associated with the amyloid are inflammatory reactions, neuritic and synaptic degeneration as well as tau hyperphosphorylation. Older mice have a reduced cholinergic fiber length and a reduced neuron number in the hippocampal CA1 region. Crossbreeding with transgenic mice expressing human presenilin 1 carrying Alzheimer's disease-linked mutations lead to an enhancement of the pathology. The APP23 line is a suitable model to analyze the contribution of APP, A beta, and amyloid to the pathogenesis of Alzheimer's disease. PMID- 11193143 TI - Prions: pathogenesis and reverse genetics. AB - Spongiform encephalopathies are a group of infectious neurodegenerative diseases. The infectious agent that causes transmissible spongiform encephalopathies was termed prion by Stanley Prusiner. The prion hypothesis states that the partially protease-resistant and detergent-insoluble prion protein (PrPsc) is identical with the infectious agent, and lacks any detectable nucleic acids. Since the latter discovery, transgenic mice have contributed many important insights into the field of prion biology. The prion protein (PrPc) is encoded by the Prnp gene, and disruption of Prnp leads to resistance to infection by prions. Introduction of mutant PrPc genes into PrPc-deficient mice was used to investigate structure activity relationships of the PrPc gene with regard to scrapie susceptibility. Ectopic expression of PrPc in PrPc knockout mice proved a useful tool for the identification of host cells competent for prion replication. Finally, the availability of PrPc knockout and transgenic mice overexpressing PrPc allowed selective reconstitution experiments aimed at expressing PrPc in neurografts or in specific populations of hemato- and lymphopoietic cells. The latter studies helped in elucidating some of the mechanisms of prion spread and disease pathogenesis. PMID- 11193144 TI - Presenilin function in APP processing. AB - Familial Alzheimer's disease (FAD) is now linked to at least three genes encoding the amyloid precursor protein (APP) on chromosome 21, and presenilin 1 and 2 on chromosome 14 and 1, respectively. FAD cases in whom presenilin mutations occur are more frequent than those with APP mutations. However, altogether they only account for approximately 0.1% of all the people suffering from Alzheimer's disease (AD), and the causes of the remaining 99.9% of the sporadic form of AD or senile dementia remain unknown. Since FAD presents with the same neuropathological features as sporadic AD, i.e., cognitive impairments and the amyloid plaques and tangles in the brain, our working hypothesis is that similar molecular pathogenic mechanisms underly both sporadic and familial AD. It follows that APP and the presenilins must be key players in the disease. Detailed knowledge about the cell biology of these proteins will be a rich source of insight into the pathology of AD, but will also shed light on the fundamental neurobiology of these proteins. PMID- 11193145 TI - The alpha-synucleinopathies: Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. AB - Parkinson's disease is the second most common neurodegenerative disease, after Alzheimer's disease. Neuropathologically, it is characterized by the degeneration of populations of nerve cells that develop filamentous inclusions in the form of Lewy bodies and Lewy neurites. Recent work has shown that the filamentous inclusions of Parkinson's disease are made of the protein alpha-synuclein and that rare, familial forms of Parkinson's disease are caused by missense mutations in the alpha-synuclein gene. Besides Parkinson's disease, the filamentous inclusions of two additional neurodegenerative diseases, namely, dementia with Lewy bodies and multiple system atrophy, have also been found to be made of alpha synuclein. Recombinant alpha-synuclein has been shown to assemble into filaments with similar morphologies to those found in the human diseases and with a cross beta fiber diffraction pattern. The new work has established the alpha synucleinopathies as a major class of neurodegenerative disease. PMID- 11193146 TI - Role of presenilin-1 in murine neural development. AB - Our previous studies showed that presenilin-1 (PS1) is required for murine neural and skeletal development. Here we report that the reduction in the neural progenitor cells observed in the PS1-/- mouse brain is due to premature differentiation of progenitor cells, rather than to increased apoptotic cell death or decreased cell proliferation. In the ventricular zone of PS1-/- mice, expression of the Notch1 downstream effector gene Hes5 is reduced, and expression of the Notch1 ligand Dll1 is elevated, indicating reduced Notch signaling. These results provide direct evidence that PS1 is involved in the regulation of neurogenesis and Notch signaling during development. PMID- 11193147 TI - Modulation of A beta deposition in APP transgenic mice by an apolipoprotein E null background. AB - Several lines of evidence implicate apolipoprotein E (apoE) and its receptor--the low density lipoprotein receptor related protein (LRP)--in Alzheimer's disease (AD) pathogenesis, including increased amyloid deposition in human AD brains of people containing the apoE epsilon 4 allele, presence of apoE and LRP in amyloid plaques, and in vitro uptake of amyloid precursor protein (APP) and amyloid beta protein (A beta) by LRP. Studies of crosses of apoE knockout mice with APP transgenic mice support a complex interaction between apoE and A beta deposition. In the Tg2576 mice expressing human APPK670N-M671L, apoE determines the amount, morphology, vascular pattern, and neuropil response to A beta deposits. In the PDAPP mice expressing human APPV717F, apoE also affects the anatomical localization of cerebral A beta deposits. Thus, APP transgenic mice can serve as models to investigate genetic influences on the amount and timing of cerebral amyloidosis, the morphology of amyloid plaques, and the vulnerability of specific neuroanatomical regions to A beta deposition. PMID- 11193148 TI - The value of transgenic models for the study of neurodegenerative diseases. AB - Transgenic animal models are useful in studying the features of APP- and PS1 linked FAD and SOD1-linked FALS. These models help to investigate the nature of the cellular/biochemical/molecular alterations in neural tissue; the character and evolution of neuronal and/or glial abnormalities; the ways mutant proteins cause damage to neurons; and the biochemical pathways associated with cell death. New technologies will help to define changes in a variety of genes/gene products and the events and conformational changes in mutant proteins that are implicated in pathogenic cascades. It is hoped such study will result in novel treatments for testing in transgenic models that can then be translated into new treatments for human neurodegenerative diseases. PMID- 11193149 TI - Identifying proteases that cleave APP. PMID- 11193151 TI - Recent advances in the understanding of the processing of APP to beta amyloid peptide. PMID- 11193150 TI - Toward the characterization and identification of gamma-secretases using transition-state analogue inhibitors. AB - The amyloid-beta protein (A beta), strongly implicated in the etiology of Alzheimer's disease (AD), is formed from the amyloid-beta precursor protein (APP) through sequential proteolysis by beta- and gamma-secretases. Cleavage by gamma secretase takes place within the middle of the single transmembrane region of APP and results primarily in 40- and 42-amino acid A beta C-terminal variants, A beta 40 and A beta 42. The latter form of A beta is highly fibrillogenic, is invariably elevated in autosomal-dominant forms of AD, and is the major A beta component found presymptomatically in cerebral deposits. Thus, blocking production of A beta in general and A beta 42 in particular is considered an important therapeutic goal. We have developed transition-state analogue inhibitors of gamma-secretase as molecular probes for characterizing the active site of this enzyme, as pharmacological tools for understanding its role in biology, and as affinity labels toward its definitive identification. Specifically, we found that: (1) difluoro ketone and difluoro alcohol peptidomimetics are effective inhibitors of gamma-secretase activity in APP transfected cells, strongly suggesting an aspartyl protease mechanism; (2) gamma secretases that form A beta 40 and A beta 42 are pharmacologically distinct but are nevertheless closely similar; (3) large hydrophobic P1 substituents increase the inhibitory potency of these peptidomimetics, suggesting a large complementary S1 pocket for gamma-secretases; (4) A beta 42 production is increased several fold over control by these gamma-secretase inhibitors after replacement with inhibitor-free media; (5) a bromoacetamide derivative of one of these analogues continues to inhibit total A beta and A beta 42 production hours after replacement with compound-free media and should help identify the target(s) of these protease transition-state mimics. PMID- 11193152 TI - Presenilin-1: a component of synaptic and endothelial adherens junctions. PMID- 11193153 TI - Alpha-secretase activity of the disintegrin metalloprotease ADAM 10. Influences of domain structure. AB - Disintegrin metalloproteases from different organisms form the ADAM (a disintegrin and metalloprotease) family. All members display a common domain organization and possess four potential functions: proteolysis, cell adhesion, cell fusion, and cell signaling. Members of the ADAM family are responsible for the proteolytic cleavage of transmembrane proteins and release of their extracellular domain. The proteolytic process is referred to as ectodomain shedding, which is activated by phorbol esters and inhibited by hydroxamic acid based inhibitors. We have shown that the disintegrin metalloprotease ADAM 10 has both constitutive and regulated alpha-secretase activity. Expression of a dominant negative mutant of ADAM 10 in HEK cells decreases the secretion of APPs alpha. In order to investigate the influence of distinct protein domains of ADAM 10 on alpha-secretase activity, several deletion mutants of ADAM 10 were constructed. Our findings demonstrate that the deletion of the disintegrin domain results in a mutant ADAM 10 with remaining alpha-secretase activity, whereas the deletion of the prodomain destroys the proteolytic activity of ADAM 10. PMID- 11193154 TI - Rapid Notch1 nuclear translocation after ligand binding depends on presenilin associated gamma-secretase activity. AB - Recent data suggest an intimate relationship between the familial Alzheimer disease gene presenilin 1 (PS1) and proteolytic processing of both the amyloid precursor protein (APP) and the important cell signaling molecule, Notch1. We now show, using mammalian cells transfected with full-length Notch1, that the C terminal domain of Notch1 rapidly translocates to the nucleus upon stimulation with the physiologic ligand Delta and initiates a CBF1-dependent signal transduction cascade. Using this assay, we demonstrate that the same aspartate mutations in PS1 that block APP processing also prevent Notch1 cleavage and translocation to the nucleus. Moreover, we show that two APP gamma-secretase inhibitors also diminish Notch1 nuclear translocation in a dose-dependent fashion. However, Notch1 signaling, assessed by measuring the activity of CBF1, a downstream gene, was reduced but not completely abolished in the presence of either aspartate mutations or gamma-secretase inhibitors. Our results support the hypothesis that similar PS1-related enzymatic activity is necessary for both APP and Notch1 processing, yet suggest that Notch signaling may remain relatively preserved with moderate levels of gamma-secretase inhibition. PMID- 11193155 TI - GSK3 beta forms a tetrameric complex with endogenous PS1-CTF/NTF and beta catenin. Effects of the D257/D385A and FAD-linked mutations. AB - We have previously shown that the endogenous C-terminal fragment of presenilin 1 co-immunoprecipitates with endogenous beta-catenin. Since PS1 has been suggested to be involved in beta-catenin stabilization, we further investigated whether GSK3 beta, responsible for beta-catenin phosphorylation and degradation, is part of the PS1/beta-catenin complex. In naive H4 and CHO cells, PS1 co immunoprecipitated with both endogenous beta-catenin and GSK3 beta. In addition, GSK3 beta endogenously binds to the PS1-CTF/NTF complex and beta-catenin in naive CHO cells. GSK3 beta also co-immunoprecipitated with PS1 full length in CHO cell lines overexpressing PS1 wild type. Given that it has been recently shown that PS1 mutations of aspartate 257 or 385 result in prevention of PS1 endoproteolysis and inhibition of gamma-secretase activity, we also tested whether PS1 endoproteolysis is required for beta-catenin/GSK3 beta/PS1 binding and whether PS1 FAD-linked mutations affect GSK3 beta recruitment in the PS1/beta-catenin complex. GSK3 beta was detected in PS1 immunoprecipitates from H4 cell lines overexpressing PS1 wild type, delta E10, A286E, L246V and in CHO cell lines overexpressing aspartate or M146L mutations. The latter data show that the absence of PS1 endoproteolysis (D257A/D385A and delta E10) or the presence of PS1 FAD mutations does not interfere with beta-catenin/GSK3 beta/PS1 complex formation. PMID- 11193156 TI - An empirical model of gamma-secretase activity. AB - gamma-Secretase catalyzes the cleavage at the carboxyl terminus of A beta to release it from the APP. While gamma-secretase is a major therapeutic drug target for the treatment of Alzheimer's disease (AD), it appears to be an unusual proteolytic activity, and, to date, no protease responsible for this activity has been identified. Based on studies of APP transmembrane domain (TMD) mutants, it is apparent that there are multiple pharmacologically distinct gamma-secretase activities that are spatially restricted and that presenilins (PS) regulate cleavage by gamma-secretases in a protease independent fashion. Based on these studies, we propose a multiprotease model for gamma-secretase activity and predict that the gamma-secretases are likely to be closely related proteases. PMID- 11193157 TI - Overexpression of presenilin-2 enhances apoptotic death of cultured cortical neurons. AB - Presenilin-2 (PS2) is a gene of unknown function linked with some forms of familial Alzheimer's disease. To investigate the biological role of PS2 in neurons, we overexpressed PS2 in primary cortical neurons using recombinant adenoviral vectors. Western blot and immunohistochemical analyses showed enhanced expression of PS2 proteins in infected neurons after infection of recombinant adenoviruses containing the human wild-type or mutant PS2 gene. Neuronal survival was decreased by approximately 30% in cultures infected with adenovirus expressing either wild-type or mutant PS2, as compared with those infected with adenovirus expressing the LacZ gene. Fragmented nuclei were frequently observed in dying neurons. These data suggest that apoptotic death of cultured cortical neurons is enhanced by PS2 overexpression. PMID- 11193158 TI - Alpha 1-antichymotrypsin inhibits A beta degradation in vitro and in vivo. AB - The neuropathology of Alzheimer's disease (AD) is characterized by extensive deposition of the toxic amyloid beta peptide (A beta) in selected regions of the brain and brain vasculature (Selkoe, 1999). Thus, lowering the levels of A beta may be beneficial for AD patients. A beta is a proteolytic fragment derived from the amyloid precursor protein (APP). The mechanisms of A beta formation from its precursor have been studied extensively; however, considerably less effort has been invested into studying A beta clearance. We find that the degradation of A beta in our system is dependent upon the presence of a metallopeptidase E.C.3.4.24.15 (MP24.15) (Yamin et al., 1999). We have previously purified MP24.15 to homogeneity from AD brain and identified it as an APP-processing protease in vitro (Papastoitsis, 1994). To confirm its role in cell culture, we transfected SKNMC neuroblastoma cells with sense and antisense cDNAs of MP24.15 and with a mock construct. Compared to mock conditioned media (CM), CM of MP24.15 overexpressing cells had very high A beta-degrading activity. Conversely, CM of antisense-expressing cells lacked A beta-degrading activity. These results suggested that MP24.15 is involved in A beta degradation. Characterization of the proteolytic activity directly responsible for A beta degradation using a spectrum of protease inhibitors revealed that only serine protease inhibitors completely blocked A beta degradation. Therefore, MP24.15 appears to activate a serine protease, which then cleaves A beta. Interestingly, alpha 1-antichymotrypsin (ACT) which we discovered to be highly elevated in AD brain (Abraham, et al., 1988) also inhibited A beta degradation. To our delight, ACT proved to be an inhibitor of A beta degradation in vivo as well. When we crossed transgenic mice expressing human ACT with plaque-producing mice expressing human APP, the doubly transgenic mice had twice as many plaques at 20 months of age as the APP mice (Mucke et al., 2000). Successful completion of this study could lead to the design of reagents that would reduce the amyloid load in AD patients. PMID- 11193159 TI - Activated mitogenic signaling induces a process of dedifferentiation in Alzheimer's disease that eventually results in cell death. AB - Neurodegeneration in Alzheimer's disease (AD) is associated with the appearance of dystrophic neuronal growth profiles that most likely reflect an impairment of neuronal reorganization. This process of morphodysregulation, which eventually goes awry and becomes a disease itself, might be triggered either by a variety of life events that place an additional burden on the plastic capability of the brain or by genetic pertubations that shift the threshold for decompensation. This paper summarizes recent evidence that impairment of the p21ras intracellular signal transduction, which is is mediated by a hierarchy of phosphorylation signals and eventually results in loss of differentiation control and an attempt of neurons to re-enter the cell-cycle, is critically involved in this process. Neurodegeneration might thus be viewed as an alternative effector pathway of those events that in the dividing cell would lead to cellular transformation. This hypothesis might be of heuristic value for the development of a therapeutic strategy. PMID- 11193160 TI - Inhibition of the neuronal insulin receptor. An in vivo model for sporadic Alzheimer disease? AB - It has been hypothesized that a central even in the early pathogenesis of sporadic Alzheimer disease (SAD) is the dysfunction of the neuronal insulin receptor signal transduction. To prove this, this receptor was inhibited by a triplicate icv application of STZ. Insulin binding sites were upregulated as in SAD. With respect to glucose transport proteins, detailed investigations are necessary. PMID- 11193161 TI - Cytoplasmic presenilin aggregates in proteasome inhibitor-treated cells. PMID- 11193162 TI - Regulation of APP synthesis and secretion by neuroimmunophilin ligands and cyclooxygenase inhibitors. AB - We and others previously showed that both the synthesis of the amyloid precursor protein (APP) and its processing (i.e., to amyloidogenic A beta peptides; soluble nonamyloidogenic APPs; and other APP fragments) are regulated by neurotransmitters. Transmitters that elevate cellular cAMP levels (like norepinephrine and prostaglandins, which act on beta-adrenergic receptors and prostaglandin E2 receptors respectively) enhance APP synthesis and the formation of amyloidogenic APP holoprotein. Transmitters that stimulate phosphatidylinositol hydrolysis (by activating muscarinic m1 or m3 receptors, serotoninergic 5HT2a or 5HT2c receptors, or metabotropic glutamate receptors of subtypes 1 or 5) increase the conversion of APP to soluble APPs, and decrease the formation of A beta. These findings suggest that drugs that regulate the activity of neurotransmitter receptors might be useful in preventing the excessive formation of A beta or other amyloid precursors in Alzheimer's disease. We now show that neuroimmunophilin ligands (like cyclosporin A or FK-506) and nonsteroidal antiinflammatory agents (NSAIDs), including cyclooxygenase (COX)-2 inhibitors, can also prevent APP overexpression and the overproduction of amyloidogenic peptides. We observe that the enhancement of APP overexpression by prostaglandin E2 is inhibited by neuroimmunophilin ligands like cyclosporin A or FK-506 (tacrolimus). We also find that the NSAIDs, which reduce prostaglandin synthesis by inhibiting COX-1 and -2 enzymes, might also be expected to lower APP levels. Our present data confirm that these drugs, as well as drugs that selectively inhibit COX-2, reduce the levels of amyloidogenic APP holoprotein in cultured neurons or in cultured astrocytes. We previously showed that elevations in cAMP, perhaps generated in response to prostaglandins, can suppress APPs secretion. The NSAIDs and COX inhibitors also increased levels of soluble APPs in the media of cultured astrocytes and neurons, perhaps acting by inhibition of prostaglandin production. Since APP holoprotein can be amyloidogenic, while APPs may be neurotrophic, our findings suggest that some neuroimmunophilin ligands, NSAIDs and COX-2 inhibitors might suppress amyloid formation and enhance neuronal regeneration in Alzheimer's disease. PMID- 11193163 TI - Abeta modulation: the next generation of AD therapeutics. PMID- 11193164 TI - Prevention and reduction of AD-type pathology in PDAPP mice immunized with A beta 1-42. AB - In AD certain brain structures contain a pathological density of A beta protein deposited into plaques. The effect of genetic mutations found in early onset AD patients was an overproduction of A beta 42, strongly suggesting that overproduction of A beta 42 is associated with AD. We hypothesized that an immunological response to A beta 42 might alter its turnover and metabolism. Young PDAPP transgenic mice were immunized with A beta 1-42, which essentially prevented amyloid deposition; astrocytosis was dramatically reduced and there was reduction in A beta-induced inflammatory response as well. A beta 1-42 immunization also appeared to arrest the progression of amyloidosis in older PDAPP mice. A beta immunization appears to increase clearance of amyloid plaques, and may therefore be a novel and effective approach for the treatment of AD. PMID- 11193165 TI - Genetics of Parkinson's disease. AB - Several genetic factors have been recently recognized as related to the etiology of Parkinson's disease. Mutations in the genes coding for alpha-synuclein and ubiquitin carboxy-terminal hydrolase have been identified in families with autosomal dominant Parkinson's disease. Mutations in the Parkin gene are responsible for autosomal recessive parkinsonism. These first pieces of the molecular puzzle of Parkinson's disease offer novel insights into the pathophysiology of the illness. PMID- 11193166 TI - Treatment with the selective muscarinic agonist talsaclidine decreases cerebrospinal fluid levels of total amyloid beta-peptide in patients with Alzheimer's disease. AB - Brain amyloid load in Alzheimer's disease (AD) is, at least in genetic forms, associated with overproduction of amyloid beta-peptides (A beta). Thus, lowering A beta production is a central therapeutic target in AD and may be achieved by modulating such key enzymes of amyloid precursor protein (APP) processing as beta , gamma-, and alpha-secretase activities. Talsaclidine is a selective muscarinic M1 agonist that stimulates the nonamyloidogenic alpha-secretase pathway in model systems. Talsaclidine was administered double-blind, placebo-controlled, and randomized to 24 AD patients and cerebrospinal fluid (CSF) levels of total A beta were quantitated before and after 4 weeks of drug treatment. We observed that talsaclidine decreases CSF levels of A beta significantly over time within the treatment group (n = 20) by a median of 16% as well as compared to placebo (n = 4) by a median of 27%. We conclude that treatment with selective M1 agonists may reduce A beta production and may thus be further evaluated as a potential amyloid lowering therapy of AD. PMID- 11193167 TI - Metal chelation as a potential therapy for Alzheimer's disease. AB - Alzheimer's disease is a rapidly worsening public health problem. The current lack of effective treatments for Alzheimer's disease makes it imperative to find new pharmacotherapies. At present, the treatment of symptoms includes use of acetylcholinesterase inhibitors, which enhance acetylcholine levels and improve cognitive functioning. Current reports provide evidence that the pathogenesis of Alzheimer's disease is linked to the characteristic neocortical amyloid-beta deposition, which may be mediated by abnormal metal interaction with A beta as well as metal-mediated oxidative stress. In light of these observations, we have considered the development of drugs that target abnormal metal accumulation and its adverse consequences, as well as prevention or reversal of amyloid-beta plaque formation. This paper reviews recent observations on the possible etiologic role of A beta deposition, its redox activity, and its interaction with transition metals that are enriched in the neocortex. We discuss the effects of metal chelators on these processes, list existing drugs with chelating properties, and explore the promise of this approach as a basis for medicinal chemistry in the development of novel Alzheimer's disease therapeutics. PMID- 11193168 TI - Regulation of gene expression by muscarinic acetylcholine receptors. A comprehensive approach for the identification of regulated genes. PMID- 11193169 TI - Cholinergic modulation of amyloid processing and dementia in animal models of Alzheimer's disease. PMID- 11193170 TI - M1 muscarinic agonists as potential disease-modifying agents in Alzheimer's disease. Rationale and perspectives. AB - A cholinergic hypofunction in Alzheimer's disease (AD) may lead to formation of beta-amyloids that might impair the coupling of M1 muscarinic ACh receptors (mAChRs) with G proteins. This disruption in coupling can lead to decreased signal transduction, to a reduction in levels of trophic amyloid precursor proteins (APPs), and to generation of more beta-amyloids that can also suppress ACh synthesis and release, aggravating further the cholinergic deficiency. These "vicious cycles," a presynaptic and a postsynaptic one, may be inhibited, in principle, by M1 selective agonists. Such properties can be detected in the functionally selective M1 agonists from the AF series [e.g., project drugs, AF102B, AF150(S)]. These M1 agonists promote the nonamyloidogenic APP processing pathways and decrease tau protein phosphorylation. The effects on tau proteins suggest a link between M1 mAChR-mediated signal transduction system(s) and the neuronal cytoskeleton via regulation of phosphorylation of tau microtubule associated protein. This may indicate a dual role for M1 agonists: as inhibitors of two "vicious cycles," one induced by beta-amyloids, and the other due to overactivation of certain kinases (e.g., glycogen synthase kinase-3, GSK-3) or downregulation of phosphatases, respectively. Prolonged administration of AF150(S) in apolipoprotein E-knockout mice restored cognitive impairments, cholinergic hypofunction, and tau hyperphosphorylation, and unveiled a high affinity binding site to M1 mAChRs. Except M1 agonists, there are no reports of compounds having such combined effects, for example, amelioration of cognition dysfunction and beneficial modulation of APPs together with tau phosphorylation. This unique property of M1 agonists to alter different aspects of AD pathogenesis could represent the most remarkable, yet unexplored, clinical value of such compounds. PMID- 11193171 TI - Cholinesterase inhibitors stabilize Alzheimer's disease. AB - During the last decade, a systematic effort to develop a pharmacological treatment for Alzheimer disease (AD) has resulted into three drugs being registered for the first time in the USA and Europe for this specific indication. All three are cholinesterase inhibitors (ChEI). The major therapeutic effect of ChEI on AD patients is to maintain cognitive function at a constant level during a six-month to one-year period of treatment, as compared to placebo. Additional drug effects might slow cognitive deterioration and improve behavioral and daily living conditions. Comparison of clinical effects of six ChEI demonstrates a rather similar magnitude of improvement in cognitive measures. For some drugs, this may represent an upper limit, whereas for other it may still be possible to further increase the benefit. In order to maximize and prolong positive drug effects, it is important to start early and adjust dosage during the treatment. Recent studies show that in many patients the stabilization effect produced by ChEI can be prolonged for as long as a 24-month period. In order to explain the stabilizing effect of ChEI, a mechanism other than AChE inhibition, based on beta amyloid metabolism, is postulated. PMID- 11193172 TI - Nasal A beta treatment induces anti-A beta antibody production and decreases cerebral amyloid burden in PD-APP mice. PMID- 11193173 TI - Physiology and pathophysiology of alpha-synuclein. Cell culture and transgenic animal models based on a Parkinson's disease-associated protein. AB - The 15-20 kDa synuclein (SYN) phosphoproteins are abundantly expressed in nervous tissue. Members of the family include alpha- and beta-SYN, and the more distantly related gamma-SYN and synoretin. SYN genes have been identified in Torpedo, canary, and several mammalian species, indicating an evolutionary conserved role. Expression of alpha-SYN was found to be modulated in situations of neuronal remodeling, namely, songbird learning and after target ablation of dopaminergic striatonigral neurons in the rat. The presynaptic localization of alpha-SYN is further supportive of a direct physiological role in neuronal plasticity. The extensive synaptic co-localization of alpha- and beta-SYN might indicate functional redundancy of these highly homologous synucleins. However, alpha-SYN was the only family member identified in Lewy bodies and cytoplasmic inclusions characteristic for multiple system atrophy. Moreover, alpha-SYN was genetically linked to familial Parkinson's disease. The two Parkinson's disease-associated mutations accelerated the intrinsic aggregation property of alpha-SYN in vitro. Post-translational modifications, such as phosphorylation and proteolysis, and/or interaction with other proteins, might regulate alpha-SYN fibril formation in vivo. Cytoskeletal elements and signal transduction intermediates have been recently identified as binding partners for alpha-SYN. Preliminary data available from transgenic mice suggest that (over)expressed human alpha-SYN proteins are less efficiently cleared from the neuronal cytosol. Thus, Parkinson's disease associated mutations might perturb axonal transport, leading to somal accumulation of alpha-SYN and eventually Lewy body formation. PMID- 11193174 TI - Cytidine (5')diphosphocholine modulates dopamine K(+)-evoked release in striatum measured by microdialysis. AB - Experiments were performed to determine whether exogenous cytidine (5')diphosphocholine (CDP-choline) could modify the release of dopamine (DA) in the striatum. Rats were divided into two groups, receiving either a standard diet (UAR 004) or the same diet supplemented with CDP-choline (250 mg/kg day) for 28 days. On the last day the dialysis probes were inserted in the striatum, and DA, homovanillic acid (HVA), and 3,4-dihydroxyphenylacetic acid (DOPAC) efflux were measured in the dialysis stream basally and during K+ depolarization (80 mM K+). Basal DA, HVA, and DOPAC did not show any difference between treated and untreated groups. Depolarization with K+ increased DA levels by up to 3,000% in the control group and by up to 4,770% in the CDP-choline-treated group (p < 0.05), and reduced extracellular HVA and DOPAC concentration by up to 45 and 35%, respectively, both in the untreated and CDP-choline-treated groups. These results show that long-term treatment with CDP-choline increases the K+ induced release DN and suggest, in accordance with previous research, that by providing exogenous choline and cytidine, CDP-choline modulates dopaminergic transmission. PMID- 11193175 TI - Accelerated oligomerization by Parkinson's disease linked alpha-synuclein mutants. PMID- 11193176 TI - Classification and description of frontotemporal dementias. AB - A number of distinct clinical syndromes have been described that are associated with focal degeneration of the frontal and temporal lobes and have a non Alzheimer pathology. The nosological status of frontotemporal lobar degeneration (FTLD) has been a matter of controversy, in view of the diversity of clinical manifestations and distribution and nature of histopathological change. This paper describes the major clinical syndromes of frontotemporal dementia, progressive aphasia, and semantic dementia; it discusses their underlying pathologies and considers their molecular status. Common histopathological changes are demonstrated across the three clinical syndromes, highlighting the link between these clinical disorders. It has been suggested that these disorders should be regarded as tauopathies on the basis of the tau pathology seen in a number of cases and the mutations in the tau gene in some familial cases. However, in a series of 47 consecutive autopsy series of FTLD, only 36% had tau pathology and 10% mutations in the tau gene, suggesting that FTLD does not constitute a unitary etiological disorder and that its characterization as a tauopathy may be potentially misleading. PMID- 11193177 TI - Progress in hereditary tauopathies: a mutation in the Tau gene (G389R) causes a Pick disease-like syndrome. AB - We describe the clinical and pathologic phenotypes of the G389R mutation in exon 13 of the Tau gene. Progressive aphasia and memory disturbance are the initial signs and begin in the fourth or fifth decade of life, followed by apathy, indifference, hyperphagia, rigidity, pyramidal signs and dementia. Death occurs after two to five years. Magnetic resonance imaging and neuropathologic studies show frontal and temporal atrophy. Pick body-like and axonal filamentous inclusions found in the neocortex and subcortical white matter, respectively, are tau immunoreactive. Immunoblot analysis of sarkosyl-insoluble tau shows two major bands of 60 and 64 kDa that, upon dephosphorylation, resolve into four bands of three- and four-repeat isoforms. Isolated tau filaments are often straight and occasionally twisted. Recombinant mutant tau protein shows a reduced ability to promote microtubule assembly, suggesting that this may be the primary effect of the mutation. The present findings indicate that the G389R mutation in Tau can cause a dementia similar to that in Pick's disease. PMID- 11193178 TI - Molecular genetics of chromosome 17 tauopathies. AB - The identification of mutations in the gene encoding the microtubule associated protein tau in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) demonstrated that tau dysfunction can lead to neurodegeneration. At least 11 missense mutations and 1 deletion mutation (delta K280) have been identified in exons 9-13 that encode the microtubule binding domains of tau. In addition, five mutations have been found close to the 5' splice site of exon 10. The different FTDP-17 mutations have multiple effects on the biology and function of tau. These varied pathogenic mechanisms likely explain the wide range of clinical and neuropathological features observed in different families with FTDP 17. In addition to the highly penetrant mutations that are found in large families with FTDP-17, a common extended haplotype in the tau gene also appears to be a risk factor in the development of the apparently sporadic tauopathy, progressive supranuclear palsy (PSP). The mechanism by which this common variability in the tau gene influences the development of PSP is unclear; however, it further suggests a central role for tau in the pathogenesis of several neurodegenerative conditions including Alzheimer's disease (AD). PMID- 11193179 TI - Tau gene mutations in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Their relevance for understanding the neurogenerative process. AB - Tau is a microtubule-associated protein that binds to microtubules and promotes microtubule assembly. Six tau isoforms are produced in adult human brain by alternative mRNA splicing from a single gene. Inclusion of a 31 amino acid repeat encoded by exon 10 of the tau gene gives rise to the three isoforms with four microtubule-binding repeats each. The other three tau isoforms have three repeats each. Abundant neurofibrillary lesions made of tau protein constitute a defining neuropathological characteristic of Alzheimer's disease. Filamentous tau protein deposits are also the defining characteristic of other neurodegenerative diseases, many of which are frontotemporal dementias or movement disorders, such as Pick's disease, progressive supranuclear palsy, and corticobasal degeneration. It is well established that the distribution of tau pathology correlates with the presence of symptoms of disease. However, until recently, there was no genetic evidence linking tau to neurodegeneration. This has now changed with the discovery of more than 15 mutations in the tau gene in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). The new work has shown that dysfunction of tau protein causes neurodegeneration. PMID- 11193180 TI - Amyloidogenesis in familial British dementia is associated with a genetic defect on chromosome 13. AB - Familial British dementia (FBD) is a disorder characterized by the presence of amyloid deposits in cerebral blood vessels and brain parenchyma coexisting with neurofibrillary tangles in limbic areas. The amyloid subunit (ABri) is a 4 kDa fragment of a 266 amino acid type II single-spanning transmembrane precursor protein encoded by the BRI gene located on chromosome 13. In FBD patients, a single base substitution at the stop codon of this gene generates a larger 277 residue precursor (ABriPP-277). Proteolytic processing by a furin-like enzyme at the C-terminus of the elongated precursor generates the 34 amino acid ABri that undergoes rapid aggregation and fibrillization. ABri is structually unrelated to all known amyloids including A beta, the main component of the amyloid lesions in Alzheimer's disease (AD), indicating that cerebral deposition of amyloid molecules other than A beta can trigger similar neuropathological changes leading to neuronal loss and dementia. These data support the concept that amyloid deposition in the vascular wall and brain parenchyma is of primary importance in the initiation of neurogeneration. PMID- 11193181 TI - Clinical and neuropathological correlates of dementia with Lewy bodies. AB - Dementia with Lewy bodies (DLB) is characterized pathologically by widespread Lewy body (LB) neuronal inclusions in the brain, but the contribution of LBs to the clinical syndrome of dementia and parkinsonism is unclear. In a clinical pathological study of 25 cases with DLB, we examined the regional neuroanatomical distribution of Lewy-related pathology using alpha-synuclein immunostaining to evaluate the relationship between LBs, neuronal loss, Alzheimer-type changes, and the clinical phenotype. Compared to traditional ubiquitin immunostaining, alpha synuclein immunohistochemistry was more specific and slightly more sensitive, staining about 5% more intracytoplasmic structures. There was a consistent pattern of vulnerability to LB formation across subcortical, paralimbic, limbic, and neocortical structures, which was independent of concomitant Alzheimer-type changes. There were no significant differences in regional LB densities among patients with or without cognitive fluctuations, visual hallucinations, delusions, recurrent falls or parkinsonism. Duration of disease correlated weakly with LB density. There was no neuronal loss in superior temporal sulcus or entorhinal cortex in pure DLB cases compared to nondemented controls. Thus, DLB is characterized by a specific neuroanatomical vulnerability to LB pathology, distinct from AD pathology, with a complicated relationship to clinical symptoms. PMID- 11193182 TI - Familial British dementia: expression and metabolism of BRI. AB - Vidal et al. (1999. Nature 399: 776-778) discovered that the underlying genetic lesion in familial British dementia (FBD) is a T-A transversion at the termination codon of a membrane protein, termed BRI. The mutation creates an arginine codon; translational read-through generates a novel protein, termed BRI L, that is extended by 11 amino acids at the carboxyl-terminus. BRI-L is the precursor of the ABri peptide, a component of amyloid deposits in FBD brain. We demonstrate that both BRI and its mutant counterpart are constitutively processed by furin, resulting in the secretion of carboxyl-terminal peptide derivatives that correspond to all, or part of, ABri. Notably, elevated levels of peptides are generated from the mutant BRI precursor, suggesting that subtle conformational alterations at the carboxyl-terminus may influence furin-mediated processing. We have examined BRI/BRI-L processing by other members of the prohormone convertase (PC) family (PACE4, LPC, PC 5/6) and found that these enzymes also process BRI, albeit inefficiently. Moreover, BRI-L processing by the other PC members is severely compromised. Finally, our electron microscopic studies reveal that synthetic ABri peptides assemble into insoluble beta-pleated fibrils. Collectively, our results support the view that enhanced furin-mediated processing of mutant BRI generates amyloidogenic peptides that initiate the pathogenesis of FBD. PMID- 11193183 TI - Nuclear envelope organization in papillary thyroid carcinoma. AB - Papillary thyroid carcinomas (PTCs) have characteristic nuclear shape changes compared to follicular-type thyroid epithelium. We tested the hypothesis that the altered nuclear shape results from altered distribution or expression of the major structural proteins of the nuclear envelope. Lamin A, lamin B1, lamin C, lamin B receptor (LBR), lamina-associated polypeptide 2 (LAP2), emerin, and nuclear pores were examined. PTC's with typical nuclear features by H&E were compared to non-neoplastic thyroid and follicular neoplasms using confocal microscopy, and semi-quantitative immunoblotting. Lamin A/C, lamin B1, LAP2, emerin, and nuclear pores all extend throughout the grooves and intranuclear inclusions of PTC. Their distribution and fluorescent intensity is not predictably altered relative to nuclear envelope irregularities. By immunoblotting, the abundance (per cell) and electrophoretic mobilities of lamin A, lamin B1, lamin C, emerin, and LAP2 proteins do not distinguish PTC, normal thyroid, or follicular neoplasms. These results do not support previously published predictions that lamin A/C expression is related to a loss of proliferative activity. At least three LAP2 isoforms are identified in normal and neoplastic thyroid. LBR is sparse or undetectable in all the thyroid samples. The results suggest that the irregular nuclear shape of PTC is not determined by these nuclear envelope structural proteins per se. We review the structure of the nuclear envelope, the major factors that determine nuclear shape, and the possible functional consequences of its alteration in PTC. PMID- 11193184 TI - Inhibited differentiation of Langerhans cells in the rat epidermis upon systemic treatment with cyclosporin A. AB - The immunosuppressant drug cyclosporin A (CsA) is known to cause reduction in number, DNA synthesis and function of Langerhans cells (LC). Since also the differentiation of LC is known to be hampered in conditions of acquired immunodeficiency not due to drugs, we investigated whether this occurs with CsA. Rats were injected subcutaneously with CsA (5, 10 and 50 mgxkg(-1) x d(-1)) for three weeks; the skin was analyzed by Ia immunohistochemistry and by electron microscopy. Epidermal immunolabeled cells were 15+/-3.5 (mean +/- SEM) per 100 basal keratinocytes in untreated controls and 8.75+/-1.3, 4.75+/-1.0 and 1.7+/ 1.2 upon increasing doses of CsA (p<0.01). By electron microscopy, monocytoid cells with deep invaginations of the plasma membrane and roundish LC poor in Birbeck granules appeared in the epidermis upon treatment. The results suggest that CsA inhibits the differentiation of LC precursors in the epidermis and that this can in part explain the selective increase in the risk of skin viral disease and cancer in chronically treated patients. PMID- 11193185 TI - Immunohistochemical expression of p53 in animal tumors: a methodological study using four anti-human p53 antibodies. AB - Mutations in the p53 tumor suppressor gene are the most common genetic alterations in human cancers. These mutations usually lead to strongly enhanced protein stabilization and allow detection by immunohistochemistry. Two monoclonal (DO-7 and PAb-240) and two polyclonal (Ab-7 and CM-1) antibodies were evaluated by standard immunoperoxidase method in domestic animal tumors, chiefly squamous cell carcinomas (SCC), and osteosarcomas as positive controls. Immunoreactivity was detected in SCC of cattle, sheep, horse and cat as well as in feline actinic keratosis, with PAb-240 and CM-1 antibodies. One polyclonal antibody (Ab-7) did not give positive result at all, whereas DO-7 monoclonal antibody did not react in dogs and cats. Immunodetection of p53 protein is thus possible in all domestic species tested, especially with CM-1 and PAb-240 antibodies, and p53 alterations seem to occur early in carcinogenesis of feline SCC as in comparable human lesions. PMID- 11193186 TI - Morphological study of erythrocyte shapes in red pulp of mouse spleens revealed by an in vivo cryotechnique. AB - The purpose of this study was to clarify erythrocyte shapes in splenic cords of living mouse spleens, using our in vivo cryotechnique followed by scanning (SEM) or transmission (TEM) electron microscopy. Some spleens of mice were quickly frozen by the in vivo cryotechnique while their hearts were beating under anesthesia. In contrast, other spleens were prepared by an in vitro freezing method after they were taken out from the abdominal cavity. They were routinely freeze-substituted, and prepared for SEM and TEM. A few mouse spleens were also routinely fixed and embedded in Quetol-812 to obtain conventional morphology. Erythrocytes in living mouse spleens showed a variety of shapes with narrow spaces between them, trapped among reticular fiber tissues. Similar various shapes of erythrocytes were kept in the red pulp even after blocking normal blood circulation, as prepared by the in vitro freezing method. In comparison to the above-mentioned findings, some erythrocytes were changed to biconcave discoid shapes by the conventional immersion fixation with chemical fixatives. They also showed wide spaces between each other among reticular fiber tissues. Such conventional morphological studies could hardly reveal the in vivo shapes of erythrocytes in functioning spleens with normal blood circulation. In contrast, the various shapes of erythrocytes in the functioning spleens were demonstrated by our in vivo cryotechnique. It is suggested that most erythrocytes congesting in spleens keep their original configuration in spite of microenviromental alteration in splenic blood circulation. PMID- 11193187 TI - Effects of neonatal diethylstilbestrol exposure on c-fos and c-jun protooncogene expression in the mouse uterus. AB - Quantitative and cell-type-specific expression of c-fos and c-jun genes after 17beta-estradiol (E2) stimulation, was investigated in the uteri of neonatally diethylstilbestrol (DES)-exposed and ovariectomized adult mice (neoDES-mice), employing Northern blot analysis, immunohistochemistry and in situ hybridization. The c-fos mRNA level before E2 injection (at baseline) was about 2.2-fold higher in neoDES-mice than in vehicle-treated control mice. In controls, E2 treatment transiently increased c-fos mRNA levels, showing a peak value (15.8-fold relative to the baseline) after 2 hours. In neoDES-mice, c-fos mRNA level reached a peak showing a 2.1-fold increase compared with its baseline value 1 hour after E2 injection. Immunohistochemistry and in situ hybridization revealed that c-fos protein (Fos) and mRNA are induced in the epithelium and vascular endothelium in both groups. Most uterine epithelia of neoDES-mice revealed low sensitivity to the c-fos expression after E2 administration compared with those of vehicle treated controls, whereas few epithelia showed high c-fos mRNA expression even at baseline. The c-jun mRNA concentration in the neoDES-mice uteri at baseline was 70% of that in vehicle-treated controls. At 1 hour after E2 injection, c-jun mRNA levels increased 1.8-fold in controls and 1.3-fold in the neoDES-mice relative to each baseline value. There were no significant differences in the distribution pattern of c-jun protein (Jun) and mRNA in the uteri of either groups; E2 stimulated c-jun mRNA expression in the stromal and myometrial cells but suppressed it in the epithelial cells, whereas intensity of c-jun immunostaining increased in the three cell types. The permanent changes in the expression of estrogen-regulated protooncogenes, c-fos and c-jun genes, by neonatal DES exposure may be responsible for the wide range of abnormalities in the genital tract of mature animals. PMID- 11193188 TI - Isoforms of Na+, K+-ATPase in human prostate; specificity of expression and apical membrane polarization. AB - The cellular distribution of Na+, K+-ATPase subunit isoforms was mapped in the secretory epithelium of the human prostate gland by immunostaining with antibodies to the alpha and beta subunit isoforms of the enzyme. Immunolabeling of the alpha1, beta1 and beta2 isoforms was observed in the apical and lateral plasma membrane domains of prostatic epithelial cells in contrast to human kidney where the alpha1 and beta1 isoforms of Na+, K+-ATPase were localized in the basolateral membrane of both proximal and distal convoluted tubules. Using immunohistochemistry and PCR we found no evidence of Na+, K+-ATPase alpha2 and alpha3 isoform expression suggesting that prostatic Na+, K+-ATPase consists of alpha1/beta1 and alpha1/beta2 isozymes. Our immunohistochemical findings are consistent with previously proposed models placing prostatic Na+, K+-ATPase in the apical plasma membrane domain. Abundant expression of Na+, K+-ATPase in epithelial cells lining tubulo-alveoli in the human prostate gland confirms previous conclusions drawn from biochemical, pharmacological and physiological data and provides further evidence for the critical role of this enzyme in prostatic cell physiology and ion homeostasis. Na+, K+-ATPase most likely maintains an inwardly directed Na+ gradient essential for nutrient uptake and active citrate secretion by prostatic epithelial cells. Na+, K+-ATPase may also regulate lumenal Na+ and K+, major counter-ions for citrate. PMID- 11193189 TI - Glomerular profile numerical density per area and mean glomerular volume in rats submitted to nitric oxide synthase blockade. AB - Rats submitted to chronic inhibition of nitric oxide synthase (NOS) have developed systemic hypertension and consequent renal injury. The present study aims to determine glomerular quantitative changes due to NOS inhibition in rats. Adults and normotensive Wistar rats were separated into control and L-NAME groups (each group n=10). The animals received water and food ad libitum, while L-NAME rats received NG-Nitro-L-Arginine methyl Ester hydrochloride to inhibit NOS (50mg/kg/day) in drinking water during 40 days. After that period the rats were sacrificed, the kidneys were removed, measured, and prepared for histological and stereological analyses. The glomerular density per area [NA(glom)] and the mean glomerular volume [v] were determined per animal in 15 random fields. In L-NAME rat the blood pressure was 76% higher than the respective control group with the same age. Glomeruli had global or segmental glomerular sclerosis; some glomeruli only presented an atrophic structure. The renal volume was not different between control and L-NAME rats (p>0.05). However, L-NAME rats had the NA(glom) 33% smaller than the control rats (p=0.0001) and, concomitantly, L-NAME rats had the v (glom) 33% higher than the control ones (p=0.004). These results demonstrate morphological renal alterations caused by NOS inhibition and hypertension. PMID- 11193190 TI - Studies on the involvement of endogenous neuropeptides in the control of thymocyte proliferation in the rat. AB - The possible involvement of endogenous vasoactive intestinal peptide (VIP), cholecystokinin (CCK) and neurotensin (NT) in the control of thymocyte proliferation has been investigated in vivo in the immature rat. For this task, we have studied the effects of the administration of selective antagonists of the receptors of the three neuropeptides on the mitotic index (% of metaphase arrested cells after vincristin injection) of thymocytes. Both CCK- and TN receptor antagonists were ineffective. In contrast, two VIP receptor antagonists (VIP-As) enhanced the mitotic index of thymocytes. VIP reversed the effect of VIP As, but when administered alone it did not alter the mitotic activity of thymocytes. In light of these findings, we conclude that endogenous VIP exerts a maximal tonic inhibitory influence on the basal proliferative activity of rat thymocytes, while endogenous CCK and NT do not play a relevant modulatory role in this process. PMID- 11193191 TI - Myenteric plexus of obese diabetic mice (an animal model of human type 2 diabetes). AB - The myenteric plexus of the gastrointestinal tract was investigated in the obese diabetic mouse, an animal model of human type 2 diabetes. Sections were immunostained by the avidin-biotin complex method, using a general nerve marker, protein gene product 9.5 (PGP 9.5), as well as antibodies to several important neurotransmitters. Computerized image analysis was used for quantification. When diabetic mice were compared with controls, no difference was found in the density of PGP 9.5-immunoreactive (IR) nerve fibres in antrum, duodenum or colon. In antrum and duodenum, diabetic mice showed a decreased number of vasoactive intestinal peptide (VIP)-IR neurons in myenteric ganglia as well a decreased relative volume density in myenteric plexus (though not significantly in antrum, p=0.073). No difference was found regarding VIP-IR nerves in colon. The volume density of nitric oxide synthase (NOS)-IR nerve fibres was decreased in antrum and duodenum of diabetic mice, whereas no difference was found in colon. The density of galanin-IR nerve fibres was decreased in duodenum. Whereas neuropeptide Y (NPY)- and vesicular acetylcholine transporter (VAChT)-IR nerve fibres was increased in density in colon of diabetic mice, no difference was found in antrum and duodenum. Regarding substance P, there was no difference between diabetic and control mice in antrum, duodenum or colon. The present study shows that gut innervation is affected in this animal model of human type 2 diabetes. It is possible that the present findings may have some relevance for the gastrointestinal dysfunctions seen in patients with type 2 diabetes. PMID- 11193192 TI - Microglial reaction in focal cerebral ischaemia induced by intra-carotid homologous clot injection. AB - This study examined the microglial reaction in a simulated thrombo-embolus ischaemia in rats given an intracarotid injection of a suspension of homologous blood clot. All rats including the controls receiving vehicle injection were perfused at 5 hours, and 1, 3 and 7 days post-operation. The brains were removed and processed for immunohistochemistry using a panel of monoclonal antibodies: OX 42, OX-18 and OX-6 for labeling of microglia. In rats given saline injection OX 42 immunoreactive microglial cells were observed to be distributed quite evenly throughout the whole brain. When injection of clot suspension was given, microglial cells responded vigorously, particularly in the ipsilateral hippocampus. Microglial reaction was also detected in the ipsilateral cerebral cortex, caudate as well as septal nuclei. The majority of the detected reactive microglial cells were hypertrophied showing thick or stout processes. Some rod like and amoeboid microglia were also observed. Rarely did the reactive microglia express OX-6 immunoreactivity. All microglial cells were unreactive for OX-18. The actual mechanisms leading to the microglial activation as well as functions of reactive microglia in focal cerebral ischaemia remain speculative. In the absence of direct evidence, it could only be suggested that they may act as sensor cells for detection of subtle alterations in the microenvironment, probably in response to focal ischaemia and/or leakage of serum-derived factors induced by thrombo-embolus stroke. PMID- 11193193 TI - A salvianolic acid B-rich fraction of Salvia miltiorrhiza induces neointimal cell apoptosis in rabbit angioplasty model. AB - Apoptosis has been suggested to participate in stabilizing cell number in restenosis. Salvia miltiorrhiza (SM) Bunge which is a Chinese herb widely used for the treatment of cardiovascular disorders contains a potent antioxidant, Salvianolic acid B. To determine whether the antioxidant affects vascular apoptosis, the present study examined the frequency of apoptotic cell death in atherosclerotic plaques and in restenotic lesions of cholesterol-fed rabbits. New Zealand White rabbits were treated with a normal diet (normal), a 2% cholesterol diet (HC), a 2% cholesterol diet and endothelial denudation (HC-ED), a 2% cholesterol diet with 5% water-soluble extract of SM (4.8 g/Kg B.W./day) and endothelial denudation (HC-ED-SM), or with a 2% cholesterol diet containing probucol (0.6 g/kg B.W./day) and endothelial denudation (HC-ED-probucol). Apoptosis and associated cell types were examined in serial paraffin sections by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and immunohistochemistry. The expression of p53, an apoptosis-related protein, was also examined. Apoptosis was mainly detected in the neointima of the three groups with endothelial denudation. The percentage of apoptotic cells in SM-treated group (68.5+/-5.9%) was significantly higher than that of normal (0%), HC (1.9+/ 1.2%), HC-ED (46.1+/-5.4%), and probucol-treated (32.8+/-3.9%) groups. The SM treatment markedly reduced the thickness of the neointima which was mainly composed of smooth muscle cells with few macrophages. In accordance with the apoptotic cell counts, positive immunoreactivity for p53 was observed in restenotic lesions from HC-ED, SM-treated and probucol-treated groups but not in the intima of the other two groups. These results suggest that the treatment with salvianolic acid B-rich fraction of SM induces apoptosis in neointima which in turn may help prevent the neointimal thickening. PMID- 11193194 TI - Histopathological changes in avian kidney caused by Bothrops insularis (jararaca ilh a) venom and a phospholipase A2-containing fraction. AB - The histopathological changes induced in avian kidney by the intramuscular injection of Bothrops insularis (jararaca ilh a) venom and its phospholipase A2 (PLA2)-containing fraction were examined. Acute experiments (3 h and 24 h) with B. insularis crude venom (20 microg and 80 microg) or its PLA2-contaning fraction (10 microg and 40 microg) resulted in significant structural damage to the kidneys of 5-12-day-old chicks. Histopathological analysis indicated that the venom and its fraction acted on the renal tubules and glomeruli. The morphological changes, although widespread, varied in intensity from cell to cell, and from tubule to tubule in venom-injected chicks. The tubular and glomerular changes produced by the venom and its PLA2-containing fraction may be the result of a direct cytotoxic effect potentiated by ischemia-related disturbances in the regional hemodynamics. The venom and its fraction affected more segments along reptilian-type nephrons than along mammalian ones. This divergent sensitivity to the venom and its fraction may reflect the species specific characteristics of B. insularis snake, an example of geographical isolation influencing its diet which is almost exclusively avian. PMID- 11193195 TI - Function of inflammatory cells and neoral cyclosporin-A in heart transplant associated coronary vasculopathy. AB - The role of Sandimmun Neoral (S-n) and the immune response in transplant associated coronary vasculopathy (TACV) was evaluated in a Lewis (Lew)-to-Fischer 344 (F344) rat abdominal heterotopic heart transplant model. Some of the transplant recipients were treated with S-n (5mg/kg/day) for 14 days post transplant, or until sacrifice. Grafts were subjected to immunohistochemical (ED1, CD4, CD8 and alpha-actin+ cells) analysis from day 7 to 100 post transplant. Singenic controls did not develop TACV, irrespective of whether they had received the drug or not. TACV was detected in Lew-F344 transplants regardless of S-n administration with participation of ED1+, CD8+ and alpha actin+ cells, although its incidence was lower in animals receiving prolonged S-n treatment. In this model, accelerated arteriosclerosis of the graft appeared to be related more to the rejection effect than to the action of the immunosuppressive agent. PMID- 11193196 TI - Detection of altered retinoic acid receptor expression in tissue sections using in situ hybridization. AB - Nuclear retinoid receptors mediate retinoid effects in controlling cell growth, differentiation, apoptosis, and carcinogenesis. Altered expression or activity of these receptors could abolish the retinoid signal transduction pathway and be associated with human carcinogenesis. In situ hybridization is a powerful tool for analyzing gene expression in formalin-fixed, paraffin-embedded tissue sections, especially for newly cloned genes or when no antibodies are available. Detection of altered retinoid receptor expression using in situ hybridization in premalignant and malignant tissues has provided important information about the roles of these receptors in cancer development and the response of these tissues to retinoid treatment. Among these receptors, altered expression of retinoic acid receptor-beta (RAR-beta) has been mostly detected in human cancers, including those of the head and neck, lung, esophagus, mammary gland, pancreas, and cervix. RAR-beta is thus currently used as a surrogate endpoint biomarker in different clinical prevention trials of various cancers. PMID- 11193197 TI - Ageing of the human oviduct: lectin histochemistry. AB - The aim of the present research was to investigate the changes of the sugar residues in the oviduct in the course of ageing in postmenopausal women vs normally menstruating women, by means of lectin histochemistry. Twenty asymptomatic postmenopausal women (48-83 years old) were recruited among patients who underwent a vaginal hysterectomy. Eight normally menstruating women were recruited as controls. Fragments of Fallopian tubes (pars ampullaris) were fixed in 10% formalin and routinely processed. The sections were labelled with HRP lectins (PNA, SBA, DBA, WGA, Con A, LTA, UEAI). Some sections were pre-treated with neuraminidase prior to staining with HRP-lectins. Among the postmenopausal patients, our histochemical data showed that there was no difference in the localization and distribution of sugar residues of glycoconjugates as detected by various HRP-lectins. Moreover, our results demonstrated that the oviductal epithelium is characterized by apical reactivity in both ciliated and non ciliated cells. In the course of ageing, the ciliated cells changed their morphology from bathyprismatic to large and rounded shape. ConA lectin reacted intensely with such highly degenerating ciliated cells and could be considered a marker of these cells. The degenerating ciliated cells are also characterized by the absence of sialic acid. In comparison with the sugar residues present in the control group, the oviductal epithelium of postmenopausal women is characterized by the loss of reactivity with DBA, WGA and ConA. Moreover, PNA reactive material was present at the free border of the ciliated and non-ciliated cells. The latter findings were statistically confirmed and could be considered strictly related to the ageing process. PMID- 11193198 TI - Bone marrow engraftment: histopathology of hematopoietic reconstitution following allogeneic transplantation in CML patients. AB - Following myelo-ablative treatment and allogeneic bone marrow transplantation (BMT) in chronic myelogenous leukemia (CML) histopathological features assumed to exert a significant impact on engraftment have been rarely investigated systematically. This review is focused on immunohistochemical and morphometric techniques involving nucleated erythroid precursors, resident macrophages and their various subsets, megakaryocytes and finally argyrophilic (reticulin collagen) fibers. Regarding standardized intervals of examination in the postgraft sequential trephine biopsies a pronounced reduction in cellularity was obvious and accompanied by a decrease in the quantity of erythro- and megakaryopoiesis. A significant correlation between the number of erythroid precursors and CD68+-macrophages could be determined in the areas of regenerating hematopoiesis. This finding is in keeping with the important functional role of the centrally localized mature macrophages during erythropoiesis. A relevant pretransplant reduction of the red cell lineage and an early to advanced reticulin fibrosis were correlated with a low hemoglobin level (anemia) and splenomegaly and furthermore associated with a significant delay to reach transfusion independence. This result was supported by corresponding findings in biopsy specimens performed shortly after day 30 following BMT (standard interval for assessment of engraftment). Samples revealed an enhancement of fiber density and a conspicuous decrease in the amount of erythropoiesis in the small fraction of patients who did not conform with the usually accepted criteria for successful hematopoietic reconstitution. Considering the compartment of histiocytic reticular cells the recurrence of Pseudo-Gaucher cells (PCGs) in the engrafted donor marrow was remarkable and most prominently expressed in the first two months following BMT. This feature was presumed to be functionally linked with a pronounced degradation of cell debris in the sequel of myelo-ablative therapy (scavenger macrophages). According to planimetric measurements in the postgraft bone marrow the atypical dwarf-like CD61+-megakaryocytes characteristic for CML disappeared. On the other hand, normalization of megakaryocyte size and nuclear lobulation were absent in sequential examination of the few patients developing a leukemic relapse. In a number of patients with manifest myelofibrosis at onset, an initial regression after BMT was followed by an insidiously occurring retrieval which was concentrated on the areas of reconstituting hematopoiesis. Similar to its relevant pretransplant association the postgraft reappearance of myelofibrosis was significantly correlated with the quantity of CD61+ megakaryocytes. Altogether a number of histological features in the pre-and postgraft bone marrow exhibited significant correlations with each other and thus indicated functional relationships. Moreover, quantity of erythropoiesis and amount of reticulin fibers (myelofibrosis) exerted a significant impact on engraftment status. PMID- 11193199 TI - A new morpho-functional classification of the Fallopian tube based on its three dimensional myoarchitecture. AB - The recent direct observations, under scanning electron microscopy (SEM), of the three-dimensional architecture of myosalpinx in different mammals allows us classify salpinxes according to the myoarchitecture of their tubo-uterine junction (TUJ) and isthmus segments. Based upon the myoarchitecture of the outer wall of the TUJ we could find barrier-like species (rat and sow), sphincter-like species type a (rabbit and ewe) and sphincter-like species type b (cow and woman). The different architecture of TUJ can be explained by the different nature of the mating process. Based upon the myoarchitecture of the isthmus we could distinguish type 1 (rat) and type 2 (rabbit, ewe, sow, cow and woman) salpinxes. In the latter the close fusion of musculature deriving from the meso (extrinsic musculature) with the musculature of salpinx (intrinsic musculature) suggests the existence of a unique mesosalpinx contractile system. The myosalpinx is mostly made up of a single network of muscular fibers. Such a plexiform structure, owing to the uneven distribution of fibers, rather than producing a series of regular contraction waves, is more likely to generate random contraction waves. The random propagation of muscular network contraction may deform the plexiform wall of the myosalpinx causing the stirring of tubal contents. By such a stirring movement the contact between hormones and nutrients and the eggs or embryos is intensified, thus favoring a correct fertilization and early embryo development. Taken all together, these systematic results probably suggest an additional and rather new function for the musculature of the tube, namely to increase fertility in a large number of species. PMID- 11193200 TI - Pax genes in development and maturation of the vertebrate visual system: implications for optic nerve regeneration. AB - Pax genes play a pivotal role in development of the vertebrate visual system. Pax6 is the master control gene for eye development: ectopic expression of Pax6 in Xenopus laevis and Drosphila melanogaster leads to the formation of differentiated eyes on the legs or wings. Pax6 is involved in formation of ganglion cells of the retina, as well as cells of the lens, iris and cornea. In addition Pax6 may play a role in axon guidance in the visual system. Pax2 regulates differentiation of the optic disk through which retinal ganglion cell axons exit the eye. Furthermore, Pax2 plays a critical role in development of the optic chiasm and in the guidance of axons along the contralateral or ipsilateral tracts of the optic nerve to visual targets in the brain. During development Pax7 is expressed in neuronal cells of one of the major visual targets in the brain, the optic tectum/superior colliculus. Neurons expressing Pax7 migrate towards the pia and concentrate in the stratum griseum superficiale (SGFS), the target site for retinal axons. Together, expression of Pax2, 6 and 7 may guide axons during formation of functional retinotectal/collicular projections. Highly regulated Pax gene expression is also observed in mature animals. Moreover, evidence suggests that Pax genes are important for regeneration of the visual system. We are currently investigating Pax gene expression in species that display a range of outcomes of optic nerve regeneration. We predict that such information will provide valuable insights for the induction of successful regeneration of the optic nerve and of other regions of the central nervous system in mammals including man. PMID- 11193201 TI - Hepatocyte growth factor activators, inhibitors and antagonists and their implication in cancer intervention. AB - Hepatocyte growth factor (HGF), otherwise known as scatter factor (SF), has been demonstrated over the past decade to elicit a number of functions that may be tumorigenic, and enhance the invasive/metastatic nature of cancer cells. Clinical studies have also demonstrated that HGF/SF, together with its receptor, cMET, is closely related to the disease progression and prognosis of patients with cancer. The past few years have seen the identification of numerous inhibitors and antagonists to the action of HGF/SF. These factors have demonstrated a possible role in minimising the action of HGF/SF on cancer cells, and may be of therapeutic value in the future. This article overviews the activators, inhibitors, and antagonists to HGF/SF and discusses the possible implications in cancer therapy. PMID- 11193202 TI - Farnesyltransferase inhibitors define a role for RhoB in controlling neoplastic pathophysiology. AB - A long-standing goal in cancer research is to identify cellular functions that have selective roles in regulating neoplastic pathophysiology. Farnesyl transferase inhibitors (FTIs) are a novel class of cancer chemotherapeutics which have little effect on normal cell physiology but which inhibit or reverse malignant cell phenotypes. FTIs were originally developed as a strategy to inhibit oncogenic Ras, the activity of which depends upon posttranslational farnesylation. However, recent work indicates the antineoplastic effects of FTIs are not linked to Ras inhibition but instead to alteration of RhoB, a small GTPase of the Rho family of cytoskeletal regulators that controls trafficking of cell surface receptors. Rho proteins integrate signals from integrins and cytokine receptors with cell shape via the actin cytoskeleton. A connection between FTIs and Rho alteration is interesting given that histological differences have long been used to define clinical cancer. RhoB is dispensable for normal cell growth and differentiation in mice. Thus, research into the antineoplastic effects of FTIs has led to the identification of a function(s) that is unnecessary for normal cell physiology but crucial for controlling malignant phenotypes. PMID- 11193203 TI - Vasculature of the normal and arthritic synovial joint. AB - The vasculature of the normal and arthritic knee is described. The joint contains a number of different tissues, many of which are heterogeneous and each with varying degrees of vascularization. In the normal joint the vasculature is highly organised, some tissues are highly vascular with well defined vascular organisation, whilst other tissues are avascular. During arthritis vascular turnover is increased. This vascular plasticity leads to redistribution of the vascular bed and may compromise its functional ability. The normal joint is able to regulate its blood flow, but this ability may be compromised by the inflammation and increased synovial fluid volume that are associated with joint disease. Growth of the subchondral vasculature into the articular cartilage may also occur, leading to ossification of the articular cartilage. PMID- 11193204 TI - Involvement of gap junctional communication and connexin expression in trophoblast differentiation of the human placenta. AB - Gap junctional intercellular communication (GJIC) permits coordinated cellular activities during development and differentiation processes, and its dysfunction or mutation of connexin genes have been implicated in pathologies. In the human placenta, two distinct differentiation pathways of cytotrophoblastic cell coexist leading to a double model: fusion phenotype (villous trophoblast) and proliferative/invasive phenotype (extravillous trophoblast). This review focuses on current knowledge on the connexin expression and the implication of GJIC in trophoblastic differentiation. Experimental evidence obtained in human placenta demonstrates the involvement of connexin 43-gap junctions in the trophoblastic fusion process and of a connexin switch during the spatially and temporally controlled proliferation/invasion process. PMID- 11193205 TI - Effect of endurance running on cardiac and skeletal muscle in rats. AB - We studied the effect of resistance running on left cardiac ventricle size and rectus femoris muscle fiber composition. Ten male Wistar rats were trained on a treadmill 6 days per week for 12 weeks. Ten rats remained sedentary and served as controls. A higher endurance time (40%) and cardiac hypertrophy in the trained animals were indicators of training efficiency. Morphometric analysis of the left ventricle cross-sectional area, left ventricular wall, and left ventricular cavity were evaluated. The endurance-running group demonstrated a hypertrophy of the ventricular wall (22%) and an increase in the ventricular cavity (25%); (p<0.0001). Semi-quantitative analysis of rectus femoris fiber-type composition and of the oxidative and glycolytic capacity was histochemically performed. Endurance running demonstrated a significant (p<0.01) increase in the relative frequency of Type I (24%), Type IIA (8%) and Type IIX (16%) oxidative fibers, and a decrease in Type IIB (20%) glycolytic fibers. There was a hypertrophy of both oxidative and glycolytic fiber types. The relative cross-sectional area analysis demonstrated an increase in oxidative fibers and a decrease in glycolytic fibers (p<0.0001). Changes were especially evident for Type IIX oxidative-glycolytic fibers. The results of this study indicate that the left ventricle adapts to endurance running by increasing wall thickness and enlargement of the ventricular cavity. Skeletal muscle adapts to training by increasing oxidative fiber Type. This increase may be related to fiber transformation from Type IIB glycolytic to Type IIX oxidative fibers. These results open the possibility for the use of this type of exercise to prevent muscular atrophy associated with age or post immobilization. PMID- 11193206 TI - The histogenesis of giant cell tumour of bone: a model of interaction between neoplastic cells and osteoclasts. AB - Giant cell tumour of bone (GCT) is a benign primary neoplasm of a bone characterised by distinctive clinical, radiological and pathological features. Females are slightly more often affected than males, and the majority of patients present between the ages of 20 and 50. GCT is locally aggressive and produces expansive and lytic lesions, most commonly in the epiphyses of long tubular bones. Histologically, it is composed of oval and spindle mononuclear cells, uniformly distributed amongst which are large multinucleated osteoclast-like giant cells. Although the term "Giant Cell Tumour" (and the erroneous historical term 'osteoclastoma') may imply that it is the multinucleated giant cells which are responsible for the proliferative capacity of the tumour, there is evidence that the stromal-like cells, the major component of the mononuclear cell population, represent the true neoplastic component of the neoplasm. The diagnosis and management of conventional GCT are often challenging and there is considerable current interest in its pathobiology. The precise histogenesis of GCT and the nature of its varying cellular constituents have remained a matter of some controversy. Factors influencing the clinical course and biological aggression of GCT are also unclear. In this selective review, the clinicopathological characteristics of GCT are summarised and current areas of interest in the study of the neoplasm are presented and discussed. Lastly, a hypothetical model of the mechanism of histogenesis and the biological behaviour of GCT is presented. PMID- 11193207 TI - Photodynamic therapy: shedding light on the biochemical pathways regulating porphyrin-mediated cell death. AB - Photodynamic therapy (PDT) is a clinically approved treatment for the ocular condition age-related macular degeneration, and certain types of cancer. PDT is also under investigation for other ocular, as well as, immune-mediated and cardiovascular indications. PDT is a two step procedure. In the first step, the photosensitizer, usually a porphyrin derivative, is administered and taken up by cells. The second step involves activation of the photosensitizer with a specific wavelength of visible light. Exposure to light of an activating wavelength generates reactive oxygen species within cells containing photosensitizer. PDT with porphyrin photosensitizers induces rapid apoptotic cell death, an event which may be attributed to the close association of these compounds with mitochondria. Thus, PDT is an attractive method to treat ailments such as cancer, viral infections, autoimmune disorders and certain cardiovascular diseases in which the apoptotic program may be compromised. The present review examines the cellular events triggered at lethal and sublethal PDT doses and their relationship to the subsequent effects exerted upon cells. PMID- 11193208 TI - Molecular medicine of TFF-peptides: from gut to brain. AB - TFF-peptides (i.e. TFF1, TFF2, TFF3; formerly P-domain peptides, trefoil factors) have been established as secretory products typical of the gastrointestinal tract. Their synthesis has recently been recognized in a number of mucin producing epithelial cells, for example, of the respiratory tract, the salivary glands, the uterus and of the conjunctiva. They have a pivotal role in maintaining the surface integrity of these delicate epithelia as constituents of mucus gels as well as by their anti-apoptotic properties and their motogenic activity modulating cell migratory processes. The latter is important for rapid healing in particular of gastrointestinal and respiratory epithelia by a process termed "restitution". On the other hand, one of these peptides--namely TFF3--has been detected as a new neuropeptide of the human hypothalamo-pituitary axis where it is synthesized in oxytocinergic neurons of the paraventricular and supraoptic nuclei. From there it is transported to the posterior pituitary where it is released into the blood stream. Synthesis of TFF-peptides also occurs pathologically as result to chronic inflammatory diseases, for example of the gastrointestinal tract. Aberrant synthesis of TFF-peptides is observed in many tumors. PMID- 11193209 TI - Significance of proneural basic helix-loop-helix transcription factors in neuroendocrine differentiation of fetal lung epithelial cells and lung carcinoma cells. AB - In this brief review article, we describe how cell fate determination by which the airway epithelial cells become neuroendocrine or non-neuroendocrine is regulated by a network of basic helix-loop-helix transcription (bHLH) factors in a similar manner to neuronal differentiation, and how this system could work to determine cell differentiation of human lung carcinomas. Immunohistochemical studies reveal that mammalina achaete-scute complex homologue (Mash)1 is expressed in pulmonary neuroendocrine cells (PNEC), while hairy and Enhancer of split (Hes)1 is expressed in pulmonary non-neuroendocrine cells (non-PNEC). Studies using gene-deficient mice for the bHLH factors revealed that in Mash1 homozygous null mice no PNEC are detected, while PNEC increase markedly in Hes1 homozygous null mice. These observations suggest that Mash1 is an essential positive factor for neuroendocrine differentiation of lung epithelium, and that Hes1 is one of the repressive factors for neuroendocrine differentiation. Moreover, immunohistochemical studies revealed that Notch receptors are detected in non-PNEC, and thus the Notch signalling pathway could play a role in the determination of airway epithelial cell differentiation. In human lung carcinomas, a similar bHLH network should operate to determine cell differentiation phenotypes. Generally, expression of the human homologue of Mash1 (HASH1) is detected in small cell carcinoma and carcinoids, while Hes1 seems to be expressed mainly in non-small cell carcinoma. Thus, proneuronal bHLH factors may play roles in cell fate determination of the airway epithelial system, and may regulate human airway epithelial cells in diseased conditions. PMID- 11193210 TI - Ultrastructural evidence in vitro of osteoclast-induced degradation of calcium phosphate ceramic by simultaneous resorption and phagocytosis mechanisms. AB - Osteoclasts are physiological polykaryons specialized in the resorption of calcified tissue. In the context of the clinical use of calcium-phosphate (CaP) ceramics as bone substitutes, this study used transmission electron microscopy to investigate the in vitro mechanisms of CaP ceramic degradation by osteoclastic cell types. Osteoclasts cultured on CaP ceramic developed typical ultrastructural features of bone osteoclasts, such as a polarized dome shape, a clear zone and a ruffled border. Modification of the shape and density of CaP crystals under the ruffled border indicated an acidic microenvironment. Moreover, osteoclasts were able to degrade ceramic by simultaneous resorption and phagocytosis mechanisms. Phagocytosis did not alter the ability of osteoclasts to resorb CaP ceramic. The phagocytosis mechanism consisted of three steps: crystal phagocytosis, disappearance of the endophagosome envelope membrane and fragmentation of phagocytosed crystals within the cytoplasm. The common mechanism of phagocytosis described here is similar to that observed with the monocyte/macrophage lineage, confirming that osteoclasts are part of the mononuclear phagocyte system. Osteoclasts are thus clearly involved in CaP degradation by means of resorption and phagocytosis. PMID- 11193211 TI - Counts and areas of S-100-positive epidermal dendritic cells in atypical molluscum contagiosum affecting HIV+ patients. AB - Molluscum contagiosum is a common and self-limiting viral infection, that in HIV+ patients courses as an opportunist affection with atypical clinical features. Impaired cell-mediated immune response could be involved in such atypical growth. We evaluated the density and area of Langerhans cells (LC) using S-100 immunohistochemistry in seven atypical molluscum contagiosum. LC density was quantified by three different methods using computer-assisted morphometry as well as estimating the relative area of LC with respect to epidermal area. Results were compared with two control groups (normal skin specimens and molluscum contagiosum affecting non-AIDS healthy patients). We found a virtual absence of LC in areas of molluscum lesions affecting both HIV+ and non-AIDS patients. Likewise we observed an evident decrease in LC density in perilesional epidermis of atypical molluscum with respect to both control groups. Upon comparing the counts and areas, we observed that this reduction in LC count was statistically significant only when considering LC related to length of basement membrane in atypical molluscum with respect to normal skin specimens. Our finding of a reduced number of LC in the perilesional epidermis of HIV+ patients with atypical molluscum could explain the high frequency and clinical challenge of molluscum contagiosum in immunocompromised people. In spite of these results, further studies of LC kinetics and functions are required to precisely elucidate their role in the course of molluscum contagiosum in HIV+ patients. PMID- 11193212 TI - Human lung fructose-1,6-bisphosphatase is localized in pneumocytes II. AB - The localization of fructose-1,6-bisphosphatase (Fru-1,6-Pase EC 3.1.3.11) in human alveolar epithelium was determined immunohistochemically using a polyclonal antibody raised against the enzyme purified from human liver. The immunohistochemical analysis revealed that the Fru-1,6-Pase was localized in pneumocytes II and was absent in pneumocytes I. Hypothetically Fru-1,6-Pase participating in glucose-6-phosphate synthesis from noncarbohydrate precursors increases NADPH level which is used for surfactant synthesis and for glutathione redox cycle. PMID- 11193213 TI - The fibronexus in reactive and tumoral myofibroblasts: further characterisation by electron microscopy. AB - Forty two surgical specimens containing myofibroblasts were studied to clarify the criteria for identifying the fibronexus, an ultrastructural feature regarded as a marker for myofibroblastic differentiation. Granulation tissue, tumour stroma, fibro-proliferative lesions (nodular fasciitis, myofibromatosis, inflammatory myofibroblastic tumour) and malignancies (myofibrosarcoma and fibrosarcoma) were studied. Comparable results were found throughout these specimens, although fibronexus junctions were better developed in reactive compared with tumoral myofibroblasts. By electron microscopy, myofibroblasts were identified by abundant rough endoplasmic reticulum, peripheral smooth-muscle myofilaments with focal densities, and fibronexus junctions. The latter were recognised as the points of convergence on the myofibroblast surfaces of intracellular myofilaments and extracellular fibronectin fibrils. The fibronectin fibrils were often co-linear with myofilaments. Also, fibronectin fibrils were dark-staining, straight and rigid-looking, and had a longitudinal filamentous substructure. A striking feature was the tendency of fibronectin fibrils to project into the surrounding extracellular space, away from the myofibroblast surface: in these respects, they differed significantly from lamina ("basement membrane"). The presence of fibronectin fibrils correlated positively with fibronectin immunostaining by light and electron microscopy. Laminin and collagen IV showed variable and weak staining in the intercellular spaces in a minority of cases and never strongly stained myofibroblast surfaces. The data emphasise that the fibronexus has a number of distinctive features permitting identification, and constitute a reference-point for pathologists wishing to use electron microscopy to refine light microscopy diagnoses of putative myofibroblastic lesions. The role of the fibronexus in the definition of the myofibroblast is discussed. PMID- 11193214 TI - Glypican-3 (GPC3) expression in human placenta: localization to the differentiated syncytiotrophoblast. AB - The expression of glypican-3 (GPC3), a heparan-sulfate proteoglycan associated with the Simpson-Golabi-Behmel fetal overgrowth syndrome, was studied in normal human placental tissue and cell lines derived from human placentae. Cytotrophoblasts derived from term placentae expressed GPC3 mRNA at low levels in culture. GPC3 mRNA expression increased markedly during trophoblast differentiation. By contrast, fibroblast cell lines derived from normal placentae did not express GPC3 in culture. Similarly, choriocarcinoma cell lines derived from human placentae (BeWo, JAR, and JEG) failed to express GPC3 mRNA. In situ hybridization confirmed the localization of GPC3 mRNA to the syncytiotrophoblast. Furthermore, immunohistochemical staining of paraffin imbedded placental tissue demonstrated intense staining of the syncytiotrophoblast cell layer and less intense staining of cytotrophoblasts. No staining of mesenchymal elements was noted. These data confirm the presence of GPC3 in human placenta and suggest it is expressed by the differentiated syncytiotrophoblast at term. PMID- 11193215 TI - Apoptotic cell death and cell proliferative activity in the rat fetal central nervous system from dams administered with ethylnitrosourea (ENU). AB - Ethylnitrosourea (ENU), a well known DNA alkylating agent, induces anomalies in the central nervous system (CNS), craniofacial tissues and male reproductive organs, and the enhancement of apoptosis is found in these tissues immediately after the administration of ENU (Katayama et al., 2000a). In this study, pregnant rats were treated with 60mg/kg of ENU at day 13 of gestation, and kinetics of apoptotic cells, mitotic cells and bromodeoxyuridine (BrdU)-positive cells in the fetal CNS were examined from 3 to 48 hours after the treatment (HAT). From 3 HAT, a significant increase in the number of apoptotic cells and a significant decrease in the number of mitotic cells were detected in the fetal CNS, and BrdU positive cells significantly decreased in accordance with the increase in the number of apoptotic cells. The present results strongly suggest that both excess cell death by apoptosis and cell growth arrest indicated by decreased number of mitotic cells and BrdU-positive cells may have a close relation to the later occurrence of microencephaly following ENU-administration, and that ENU affects mainly S-phase cells and causes apoptosis. PMID- 11193216 TI - TIMP-1 promotes VEGF-induced neovascularization in the retina. AB - Proteolysis of vascular basement membranes and surrounding extracellular matrix is a critical early step in neovascularization. It requires alteration of the balance between matrix metalloproteinases (MMPs) and proteins that bind to and inactivate MMPs, tissue inhibitors of metalloproteinases (TIMPs). TIMP-1 has been demonstrated to inhibit neovascularization in chick chorioallantoic membranes. However, TIMP-1 has also been shown to either promote or inhibit cell proliferation and migration in different settings. To determine whether genetic alteration of the MMP/TIMP-1 ratio would alter retinal neovascularization, we crossed mice that express vascular endothelial growth factor (VEGF) in photoreceptors with TIMP-1-deficient mice or mice that overexpress TIMP-1. Compared to VEGF transgene-positive/TIMP-1-sufficient mice, VEGF transgene positive/TIMP-1-deficient mice showed smaller neovascular lesions. There was also no difference between the two groups of mice in the appearance of the neovascularization by light or electron microscopy. Compound VEGF/TIMP-1 transgenic mice had increased expression of both VEGF and TIMP-1 in the retina, and had more neovascularization than mice that had increased expression of VEGF alone. These gain- and loss-of-function data suggest that alteration of the TIMP 1/MMP ratio modulates retinal neovascularization in a complex manner and not simply by altering the proteolytic activity and thereby invasiveness of endothelial cells. PMID- 11193217 TI - Prognostic value of p53 protein expression and clinicopathological factors in infiltrating ductal carcinoma of the breast. A study of 192 patients. AB - The p53 gene is located on the short arm of chromosome 17. It encodes a 53-kd nuclear protein (p53) found in scant amounts in normal tissue. Mutations of the p53 gene have been reported in different human tumours. In breast cancer, it has been noted that the overexpression of p53 protein in the nucleus is an indicator of poor prognosis, although there is a high degree of variability, which may be due to different immunohistochemical techniques, varying assessment of results and the type of monoclonal antibody used. This study is an immunohistochemical analysis of p53 expression in 192 cases of infiltrating ductal carcinoma of the breast, correlating it with clinicopathological factors and the clinical course of the disease. Of all the breast-cancer tissue analysed, stains for p53 antibody were found in 87 tumours (45.3%). The results of multivariate analysis show that the independent predictors related to recurrence are tumour size, lymph-node metastasis and p53, while those related to death are necrosis, lymph-node metastasis and p53. In summary, our series showed prognostic significance between the expression of p53 and shorter survival time and disease-free interval for all patients in general as well as those who presented lymph-node metastases at the time of diagnosis. PMID- 11193218 TI - Volume visualization in radiation treatment planning. AB - Radiation treatment planning (RTP), historically an image-intensive discipline and one of the first areas in which 3D information from imaging was clinically applied, has become even more critically dependent on accurate 3D definition of target and non-target structures in recent years with the advent of conformal radiation therapy. In addition to the interactive display of wireframe or shaded surface models of anatomic objects, proposed radiation beams, beam modifying devices, and calculated dose distributions, recently significant use has been made of direct visualization of relevant anatomy from image data. Dedicated systems are commercially available for the purpose of geometrically optimizing beam placement, implementing in virtual reality the functionality of standard radiation therapy simulators. Such "CT simulation" systems rely heavily on 3D visualization and on reprojection of image data to produce simulated radiographs for comparison with either diagnostic-quality radiographs made on a simulator or megavoltage images made using the therapeutic beams themselves. Although calculation and analysis of dose distributions is an important component of radiation treatment design, geometric targeting with optimization based on 3D anatomic information is frequently performed as a separate step independent of dose calculations. PMID- 11193219 TI - Tarsal joint kinematics via 3D imaging. PMID- 11193220 TI - An age-related decline in melatonin secretion is not altered by food restriction. AB - Melatonin has been found to exhibit youth-maintaining and disease-preventing properties. The current study examined whether the age-retarding regimen of chronic food restriction (FR) slowed the decline in melatonin secretion reported to occur with age. Total nocturnal melatonin secretion was assessed by radioimmunoassay of the primary metabolite, 6-sulphatoxymelatonin (6-S-OH-MLT), in urine. Measurements were made through adulthood (70 to 765 days) on male Wistar rats maintained on the FR regimen (60% of the normal intake) with the control animals fed ad libitum (AL). The data of animals exhibiting gross pathology were excluded. Analyses of covariance found the FR regimen had no effect on either the levels or pattern of decline observed in 6-S-OH-MLT excretion through adulthood. However, the FR body-weight-indexed metabolite measures were approximately double those of the AL (p = .06). The possibility that this result may reflect unusually high melatonin peaks in the FR tissues is discussed. PMID- 11193221 TI - Age-associated accumulation of the apolipoprotein C-III gene T-455C polymorphism C allele in a Russian population. AB - Apolipoprotein C-III (apoC-III) is the major component of triglyceride-rich lipoproteins. One of six identified polymorphisms in the apoC-III 5'-untranslated region (T-455C) is located within a functional insulin-response element. In a group of 137 elderly individuals (70-106 years old), the allele distribution was analyzed using restriction fragment length polymorphisms. Statistical analysis of allele frequencies was performed on subgroups selected by age and in elderly patients with arterial hypertension or ischemic heart disease. A greater frequency of the apoC-III -455C allele was demonstrated with aging (p < .005). No statistically significant difference in allele distributions was detected between healthy subjects and groups of elderly patients of the same age with either ischemic heart disease or arterial hypertension. The increased incidence of the C allele with advanced age indicates that this variant promoter is associated with longevity. The greater incidence of this allele is detectable only in adults older than 80 years of age. PMID- 11193222 TI - Accuracy of equations for predicting stature from knee height, and assessment of statural loss in an older Italian population. AB - We determined the applicability of deriving the stature from knee height in an older Italian population, and, in the same population, we assessed longitudinally the change in stature over a 6-year interval. The standing stature and knee height in a supine position were measured in the entire home-dwelling older (65 + years) population of a small Italian town (N = 606). Stature measured in 1989 and in 1995 was used to assess longitudinal changes in 258 subjects of the same population. Stature derived from knee height was greater than measured stature in this population and in the two sexes. This difference disappeared when subjects with evident kyphosis were excluded. From 1989 to 1995, stature decreased by 1.7+/-3.0 cm, with women showing a larger decrement than men. Stature estimated from knee height is more accurate than measured stature in subjects with kyphosis. In accordance with previous studies, stature decreases with aging, and such height loss is greater in women than in men. PMID- 11193223 TI - Effects of chronic food restriction and exercise training on the recovery of cardiac function following ischemia. AB - Clinical and experimental data suggest that exercise training (ET) and food restriction (FR) improve cardiovascular function. However, the effects of long term FR or FR in combination with ET on the recovery of cardiac function following ischemia have not been determined. Male Wistar rats were assigned to ad libitum-fed, FR, ad libitum-exercise, and FR-exercise groups. Mechanical function of isolated working hearts was assessed in response to increases in afterload resistance and following global no-flow ischemia. At low workload, there was a significant FR effect on aortic flow as well as an interaction between FR and ET on systolic pressure. These effects remained when hearts were subjected to increases in aortic afterload resistance. During reperfusion of ischemic hearts, there was a significant FR effect on aortic flow and systolic pressure and a significant ET effect on diastolic pressure. An interaction between FR and ET on heart rate was also seen during reperfusion. In terms of percent recovery of heart function following ischemia, FR continued to affect aortic flow, and we observed an interaction between FR and ET on aortic flow. Our results clearly indicate that the myocardium from the FR animal or the FR, exercise-trained rat is more resistant to ischemia. PMID- 11193224 TI - Low- or high-intensity strength training partially restores impaired quadriceps force accuracy and steadiness in aged adults. AB - Because many daily tasks are executed at only a fraction of maximal strength, an understanding of submaximal force control may be important for improving function in aged adults. We compared the effects of low- and high-intensity (LI and HI, respectively) strength training on maximal and explosive strength and on the accuracy (force error) and steadiness (variability) of submaximal quadriceps force in elderly humans. Older subjects (age, 72 years; n = 27) had 57% lower maximal strength in comparison with young subjects (age, 21 years; n = 10). Older subjects had 190% (19 N), 50% (1 N), and 80% (4 N) more force error in matching 25 N of quadriceps force during eccentric, isometric, and concentric contractions, and had 157%, 0%, and 60% more variability in these forces compared with young subjects. Force error and force variability were correlated with each other but not with maximal strength. Thirty sessions of LI (n = 9 participants) or HI (n = 9 participants) training of equal total work increased maximal strength in the older subjects by 29%. Training also significantly reduced force error and variability--by 31% and 30%, respectively--of eccentric and concentric contractions. A control group of older subjects (n = 9) showed no significant changes in any variables. LI or HI strength training was equally effective in partially restoring elderly adults' maximal strength and control of submaximal force. PMID- 11193225 TI - Human diploid fibroblasts that undergo a senescent-like differentiation have elevated ceramide and diacylglycerol. AB - Senescent human diploid fibroblasts (HDF) have elevated levels of ceramide and diacylglycerol (DAG) compared with young HDF. DNA fragmentation analysis demonstrated the increased ceramide in senescent HDF was not associated with apoptosis, whereas in young HDF, exogenous ceramide induced apoptosis. In young HDF treated with both exogenous ceramide and DAG, less DNA fragmentation was observed. Thus, elevated DAG levels in senescent HDF might protect against ceramide-induced apoptosis. To determine which characteristics of senescent HDF (aging per se, cell cycle arrest, elevated p21Sdi1,Waf1,Cip1, and senescent-like differentiation) might influence ceramide and DAG, we examined transformed or mitomycin C-treated HDF that shared some of these properties with senescent HDF. The elevation of ceramide and DAG did not depend on aging per se, cell cycle arrest, or elevation of p21. Rather, ceramide and DAG may be elevated as part of a program of differentiation that is induced by either aging or DNA damage. PMID- 11193226 TI - Prevalence rate of urinary incontinence in community-dwelling elderly individuals: the Veneto study. AB - BACKGROUND: Urinary incontinence (UI) is a common problem in elderly people, due mainly to functional impairments and concurrent medical diseases. Few studies, however, have assessed the prevalence of UI in noninstitutionalized individuals. The objectives of the present work were to estimate the prevalence of UI in a community-based population of elderly Italians and to determine the associated physical, social, and psychological factors. METHODS: A random sample of noninstitutionalized men (n = 867) and women (n = 1531), aged 65 years and older, from the Veneto region of northeastern Italy, were interviewed at home, using an extensive multidisciplinary questionnaire, to assess their quality of life and social, biological, and psychological correlates. RESULTS: The prevalence rate of UI was of 11.2% among men and of 21.6% among women. Among those reporting the condition, approximately 53% of women and 59% of men reported experiencing incontinence daily or weekly. Association of UI was found for participants older than 70 years in both men (odds ratio [OR] 2.49, 95% confidence interval [CI] 1.45-4.28) and women (OR 1.49, 95% CI 1.11-2.02). Three of the medical conditions investigated were associated with increases in the odds in women, namely chronic obstructive pulmonary disease (OR 1.53, 95% CI 1.11-2.12), Parkinsonism (OR 2.27, 95% CI 1.14-4.54), and hip fracture (OR 1.38,95% CI 1.02-1.88), whereas chronic diarrhea was the only condition associated with UI in men (OR 6.92, 95% CI 2.22 21.5). Participants with a physical disability were two times more likely to report incontinence, and the odds were increased by 50% in women who had sleep disturbances. CONCLUSIONS: Incontinence is highly prevalent in the Italian elderly population, and several common chronic conditions are significantly associated with it. Moreover, very few people with incontinence seek health care or are aware of potential treatments. PMID- 11193227 TI - New-onset incontinence and markers of frailty: data from the Hispanic Established Populations for Epidemiologic Studies of the Elderly. AB - BACKGROUND: Urinary incontinence in older adults has many distinct etiologies and is associated with lower self-reported health. However, it is unclear whether the new onset of urinary incontinence marks newly emergent frailty. METHODS: Using a longitudinal population-based survey of older Mexican Americans (N = 2660) across five south-western states, this study compared the strength of association between markers of physical frailty such as activities of daily living (ADLs), instrumental activities of daily living (IADLs), and performance (timed walk, timed chair rise, and tandem balance) with baseline incontinence (prevalent disease) and new-onset incontinence (incident disease). RESULTS: We found that 14.1% of the participants (n = 329) were incontinent at baseline (prevalent cases) and 11.6% (n = 208) were newly incontinent 2 years later (incident cases). Controlling for other covariates, prevalent incontinence was only associated with a 60% increased risk of having difficulty walking 8 ft. Incident incontinence was associated with a twofold increased risk of impairment in ADLs and IADLs, and poor performance on all three physical measures. CONCLUSIONS: Incident incontinence is associated with an increased risk of more global functional impairment. Thus, incident disease may be an important early marker for signaling the onset of frailty among persons who become incontinent after the age of 65 years. PMID- 11193228 TI - Age 85+ years accelerates large-fiber peripheral nerve dysfunction and diabetes contributes even in the oldest-old: the Women's Health and Aging Study. AB - BACKGROUND: Both diabetes mellitus and advancing age are associated with peripheral nerve dysfunction (PND). However, the independent and potentially synergistic effects of these factors in old age are poorly described, especially among the oldest-old and among people with an existing disability. METHODS: A total of 894 women aged 65+ years participating in the Women's Health and Aging Study received a baseline home interview and clinical examination during which PND was evaluated by the Vibratron II. Age and diabetes were examined in relation to the level of PND (normal, mild, moderate, or severe). Height, alcohol consumption, smoking, report of neurologic symptoms, and diabetes duration were examined as potential confounders. RESULTS: Eighteen percent of the sample reported diabetes, 42% had normal nerve function, and 23.9%, 14.5%, and 19.5% had mild, moderate, and severe PND, respectively. Women aged 85+ years had 6.5, 7.5, and 13.3 times the odds of mild, moderate, and severe PND relative to women aged 65-74 years, adjusted for diabetes and height. Women who reported diabetes had 1.8, 2.4, and 1.6 times the risk of mild, moderate, and severe PND relative to those who did not, adjusted for age and height. No interaction between age and diabetes was observed. CONCLUSIONS: Age is strongly associated with decrements in large-fiber peripheral nerve function in disabled women aged 65+ years, with greatly accelerated risk among those aged 85+ years. Despite the overwhelmingly strong effects of advancing age on PND in this cohort, diabetes remains a significant correlate of PND. Future studies may determine whether prevention or control of diabetes is effective in reducing the occurrence of PND in old age and whether a reduction in PND will translate into reduced disability in this age group. PMID- 11193229 TI - Epidemiology of urinary incontinence. PMID- 11193230 TI - Reliability assessment of the bladder diary for urinary incontinence in older women. AB - BACKGROUND: A reliable method of documenting the frequency of incontinent episodes is essential for assessment of treatment outcome in both clinical practice and research studies. Bladder diaries, completed prospectively by the patient, have been widely used for this purpose. This study investigated the number of consecutive days of bladder diary reports of incontinence frequency necessary to obtain adequate internal consistency (reliability). METHODS: Participants were 214 community-dwelling women, aged 40 to 90 years, with a history of stress, urge, or mixed urinary incontinence, persisting at least 3 months with a frequency of two or more episodes of urine leakage per week. Each participant kept a 14-day bladder diary documenting the time and circumstances of each incontinence episode. RESULTS: The mean age of participants was 63.5 years; 16.9% were African American. Women with predominantly urge incontinence (n = 138) reported a daily frequency of 2.1 incontinent episodes. Although there was a statistically significant difference between Week 1 (2.4 episodes per day) and Week 2 (2.0 episodes per day; p < .0001), five days were necessary to obtain an internal consistency of .90 for Cronbach's alpha. Women with predominantly stress incontinence (n = 76) had no statistical difference between Week 1 and Week 2 in frequency of incontinence, reporting an average 2.2 accidents per week in Week 1 and 2.1 in Week 2. However, 7 days of bladder diary were required before adequate internal consistency was reached. CONCLUSION: Seven consecutive days of bladder diary provides a stable and reliable measurement of the frequency of incontinence episodes in community-dwelling women. PMID- 11193231 TI - The effects of antidepressants on obstructed and unobstructed gait in healthy elderly people. AB - BACKGROUND: Elderly patients treated with antidepressants for depression are at high risk for injury due to falling. The primary purpose of this study was to determine the effects of amitriptyline, desipramine, and paroxetine on the gait of healthy elderly subjects during unobstructed and obstructed (i.e., stepping over obstacles) gait. Psychomotor and mood tests were also performed. METHODS: A randomized, crossover, four-period, double-blind, placebo-controlled laboratory trial was performed. Twelve healthy elderly subjects (average age, 67 years; range, 65-72 years) were tested. Subjects were assigned the three antidepressant drugs or a placebo in a random order. Single doses of amitriptyline 50 mg, desipramine 50 mg, paroxetine 20 mg, or placebo were given 4 hours prior to gait testing. Temporal-distance measures and kinematics of the lower trailing limb (i.e., limb going over obstacle last) were obtained. RESULTS: Compared with placebo, amitriptyline significantly reduced gait velocity by as much as 8.0% (p = .028), cadence by as much as 4.9% (p = .012), angular velocity of hip flexion by as much as 10.0% (p = .004), and angular velocity of knee flexion by as much as 8.3% (p = 018) during the crossing strides when stepping over obstacles. Except for knee flexion angle, unobstructed gait was not affected. Amitriptyline affected integrative capacity of the central nervous system (CNS) and ability to concentrate as measured by psychomotor and mood tests. CONCLUSIONS: The results for amitriptyline suggest that the subjects slowed their obstacle crossing speeds as a result of reduced CNS integrative capacities. Neither paroxetine nor desipramine significantly affected gait, psychomotor function, or mood. PMID- 11193232 TI - Elderly subjects' ability to recover balance with a single backward step associates with body configuration at step contact. AB - BACKGROUND: In the event of a slip or trip, one's ability to recover a stable upright stance by stepping should depend on (a) the configuration of the body at the instant of step contact and (b) the forces generated between the foot and ground during step contact. In this study, we tested whether these two variables associate with elderly subjects' ability to recover balance by taking a single backward step after sudden release from an inclined position. METHODS: Twenty-six community-dwelling subjects (12 women, 14 men) of mean age 75+/-4 (SD) years each underwent five trials in which they were suddenly released from a backward inclination of 7 degrees and instructed to "recover balance with a single step." Body segment motions and foot contact forces were analyzed to determine step contact times, stepping angles, body lean angles at step contact, and the magnitudes and times (after step contact) of peak foot-floor contact forces and peak sagittal-plane torques at the ankle, knee, and hip of the stepping leg. RESULTS: Fifty percent of subjects were predominantly single steppers (successful at recovering with a single step in greater than three of five trials), 27% were multiple steppers (successful in less than two of five trials), and 23% were mixed response steppers (successful in two of five or three of five trials). Recovery style associated with the ratio of stepping angle divided by body lean angle at step contact (p = .003), which averaged 1.4+/-0.5 for single steppers and 0.6+/-0.5 for multiple steppers, but not with step contact time, stepping angle, or contact forces and joint torques during step contact. CONCLUSIONS: These results suggest that elderly subjects' ability to recover balance with a single backward step depends primarily on the configuration of the body (in particular, the ratio of stepping angle to body lean angle) at step contact. PMID- 11193233 TI - The correlation of cytokine levels with body weight after megestrol acetate treatment in geriatric patients. AB - BACKGROUND: Cachexia is associated with elevated levels of cytokines in cancer and human immunodeficiency virus patients. Studies in cancer and acquired immunodeficiency syndrome patients showed that treatment with megestrol acetate (MA) is associated with improvement in appetite and weight gain. Reduction in the levels of cytokines is associated with weight gain in laboratory animals with cancer. This study evaluates the correlation between changes in cytokine (or their receptor) levels and weight following MA treatment in geriatric weight-loss patients. METHODS: Veterans Administration Medical Center nursing home patients (N = 69) with a weight loss of > or =5% of usual body weight over the past 3 months or body weight 20% below their ideal body weight participated in a 12 week, randomized, double-blind, placebo-controlled trial, with an additional 13 week follow-up period. Patients were randomly assigned to receive a placebo or MA oral suspension of 800 mg/d for 12 weeks. Levels of the following cytokines (or their receptors) were measured at baseline and after 12 weeks of treatment: tumor necrosis factor soluble receptor (TNFR) subunits. TNFR-p55 and TNFR-p75: interleukin 6 (IL-6); and the soluble interleukin-2 receptor (sIL-2R). The subjects' weight and body composition were measured at the start of the study. Weight and mortality were followed up for another 13 weeks after discontinuing the MA study drug. RESULTS: Elevated levels of IL-6 in almost all geriatric cachexic patients, compared with normal volunteers (mean, <4.6 pg/ml). were noted at baseline. At 12 weeks after the study drug treatment, there was a decrease in cytokine levels (or their receptors) in the MA group (mean change in IL-6, 3.63+/ 6.62 pg/ml; TNFR-p55, -0.06+/-0.11 ng/ml; TNFR-p75. -0.01+/-0.29 ng/ml; and sIL 2R, 0.08+/-0.07 ng/ml) and the placebo group (mean change in IL-6, -2.08+/-3.92 pg/ml; TNFR-p55, -0.02+/-0.08 ng/ml; TNFR-p75, -0.20+/-0.18 ng/ml; and sIL-2R, 0.02+/-0.03 ng/ml). Although the change in cytokine levels was not statistically significant between the two groups, significant negative correlation (p < .05) was found. For example, increased weight correlated with decreased sIL-2R levels (r = .36) and TNFR-p75 (r = -.31; fat-free mass (FFM) gain and reduction of sIL 2R (r = -.39), TNFR-p75 (r = -.30). There was a significant correlation between weight gain and reduction of TNFR-p75 (r = .54), TNFR-p55 (r- = .47), and sIL-2R (r = -.53); FFM gain and reduction of sIL-2R (r = -.59), TNFR-p75 (r = -.41), TNFR-p55 (r = -.42); and fat gain and reduction of TNFR-p75 (r = -.41) in the MA group (p < .05), but not in the placebo group. CONCLUSIONS: Although there was no significant change in cytokine levels between the two groups, the reduction in cytokine levels after MA treatment correlated with improvement in weight, fat mass, and FFM at 12 weeks. PMID- 11193234 TI - Diabetes in elderly adults. AB - Diabetes is common in the elderly population. By the age of 75, approximately 20% of the population are afflicted with this illness. Diabetes in elderly adults is metabolically distinct from diabetes in younger patient populations, and the approach to therapy needs to be different in this age group. Diabetes is associated with substantial morbidity from macro- and microvascular complications. Several lines of evidence suggest that optimal glycemic control and risk factor modification can substantially reduce the risk of complications in elderly patients. In the past, treatment options were limited. However, recent studies have delineated several new and exciting therapeutic opportunities for elderly patients with diabetes. PMID- 11193235 TI - Self-reported and clinical oral health in users of VA health care. AB - BACKGROUND: This article describes the oral health of users of Veterans Administration (VA) health care using both clinical and self-report measures, and models relationships between these measures and self-perceived oral health. METHODS: We conducted a cross-sectional study of 538 male users of VA outpatient care in the Boston area. Questionnaires assessed self-reported oral health, oral specific health-related quality of life, health behaviors, and sociodemographic information. Clinical data were collected on oral mucosa status, number of teeth and root tips, dental caries, and periodontal treatment need. We report clinical and self-reported oral health status by age group (era of military service). We regressed models of self-perceived oral health on clinical indices and self reported measures of the impact of oral health on daily life, adjusting for sociodemographic characteristics and health behavior. RESULTS: Among those participants aged 65 to 91 years old, 2.8%, 18.7%, and 41.5% rated their oral health as excellent, very good, or good, respectively. Among 50- to 64-year-old men, the corresponding values were 1.4%, 18.5%, and 40.4%, while among those aged 22 to 49 years old, the values were 2.3%, 17%, and 34.1%. Tooth loss was common among users of VA care; 34% of those aged 65-90 years, 28% of those aged 50-64 years, and 8% of those aged 25-49 years had no teeth. Periodontal treatment needs were uniformly high among persons with teeth; mild mucosal change was common, and 10% had root tips. Regression models showed self-perceived oral health was better in persons with more teeth and recent dental treatment, and worse with tooth mobility, coronal decay, and more medical problems. Measures of the impact of oral conditions on daily life added significantly to the amount of explained variance in self-perceived oral health. CONCLUSIONS: Clinical conditions and the impact of oral health on daily life are important determinants of self-perceived oral health. PMID- 11193236 TI - Molecular markers of bone turnover: biochemical, technical and analytical aspects. PMID- 11193238 TI - Preanalytical variability of biochemical markers of bone turnover. PMID- 11193237 TI - The use of biochemical markers of bone turnover in osteoporosis. Committee of Scientific Advisors of the International Osteoporosis Foundation. PMID- 11193239 TI - Prediction of bone loss in postmenopausal women. PMID- 11193240 TI - Markers of bone turnover for the prediction of fracture risk. PMID- 11193241 TI - Markers of bone turnover for monitoring treatment of osteoporosis with antiresorptive drugs. PMID- 11193242 TI - Osteoprotegerin and its ligand: a new paradigm for regulation of osteoclastogenesis and bone resorption. AB - In just 3 years, striking new advances have been made in understanding the molecular mechanisms that govern the crosstalk between osteoblasts/stromal cells and hematopoietic osteoclast precursor cells that leads to osteoclastogenesis. Led first by the discovery of osteoprotegerin (OPG), a naturally occurring protein with potent osteoclastogenesis inhibitory activity, rapid progress was made to the isolation of RANKL, a transmembrane ligand expressed on osteoblasts/stromal cells that binds to RANK, a transmembrane receptor on hematopoietic osteoclast precursor cells. The interaction of RANK and RANKL initiates a signaling and gene expression cascade that results in differentiation and maturation of osteoclast precursor cells to active osteoclasts capable of resorbing bone. OPG acts as a decoy receptor, binding to RANKL and blocking its interaction with RANK, inhibiting osteoclast development. Many of the calciotropic hormones and cytokines, including 1,25(OH)2D3, PTH, PGE2 and IL-11, appear to act through a dual capacity to inhibit production of OPG and stimulate production of RANKL. Estrogen, on the other hand, appears to inhibit production of RANKL and RANKL-stimulated osteoclastogenesis. Recently, the results of the first clinical trial with OPG supported its potential as a therapeutic agent for diseases such as osteoporosis. The new understanding provided by the RANK/RANKL/OPG paradigm for both differentiation of osteoclasts and their activation has had tremendous impact on the field and opened new avenues for development of possible treatments of diseases characterized by excessive bone resorption. PMID- 11193243 TI - Timed loaded standing: a measure of combined trunk and arm endurance suitable for people with vertebral osteoporosis. AB - Chronic back tiredness or fatigue is a common complaint of people who have a history of osteoporotic vertebral fracture. Trunk muscle endurance has not been studied in people with vertebral osteoporosis, partly due to the lack of assessment tools. We developed a measure of combined trunk and arm endurance suitable for people with vertebral osteoporosis, timed loaded standing (TLS). TLS measures the time a person can stand while holding a two-pound dumbbell in each hand with the arms at 90 degrees of shoulder flexion and the elbows extended. Intraclass correlation coefficients (ICCs) for same day inter-trial and six to ten day test-retest reliability were 0.89 (lower bound 95% confidence interval [LB 95% CI] 0.79) and 0.84 (LB 95% CI 0.68), respectively, in a sample of 21 older women with no known osteoporosis. In 127 women with vertebral fractures, the ICC for same day inter-trial reliability was 0.81 (LB 95% CI 0.75). In a sub sample of 30 of these women with vertebral fractures, the six to ten day test retest reliability was 0.85 (LB 95% CI 0.75). Moderately strong and statistically significant (p < or = 0.05) correlations were found between TLS and sixteen of eighteen measures of physical impairment and function. Functional reach distance, gait velocity, MOS-36 Physical Function Subscale, shoulder flexion strength, and six minute walk distance were most strongly associated with TLS time. Women with vertebral fractures who endorsed having back tiredness when standing and working with the arms in front of the body, sitting to rest because of back tiredness or pain, and planning rest periods because of back tiredness or pain had significantly lower TLS times. TLS is a simple, safe physical performance measure of combined trunk and arm endurance that demonstrates acceptable reliability (inter-trial and test- retest) and concurrent validity. PMID- 11193244 TI - Quantitative ultrasound of the calcaneus in Brazilian Caucasian women: normative data are similar to the manufacturer's normal range. AB - Quantitative ultrasound (QUS) can be a helpful alternative to identify osteoporotic patients. In this study we establish the QUS Brazilian normal range (BNR) and compare its values (means and standard deviations) with the manufacturer's normal range (MNR). We measured three QUS parameters (broadband ultrasound attenuation, BUA; speed of sound, SOS; stiffness index, SI) at the right calcaneus in 352 healthy Caucasian Brazilian women, aged 20-84 years. We studied the age-dependent changes in QUS values and correlation with body size and years since menopause (YSM). A comparison of fracture risk classification using the BNR and MNR is also presented. Age was the most significant predictor for all QUS parameters (r = -0.49 for BUA, r = -0.66 for SOS, r = -0.64 for SI). Weight was accepted as the second determinant for BUA (final regression model: BUA = 101.3 - 0.282 x Age + 0.373 x Weight; p < 0.001; adjusted R2 = 0.33). Body mass index (BMI) was accepted as the second predictor for SI (SI = 94.8 -0.595 x Age +0.851 x BMI; p<0.001; adjusted R2 = 0.44). Height and YSM were accepted as second and third determinants for SOS values (SOS = 1718.7 - 1.147 x Age - 69.863 x Height - 0.521 x YSM; p < 0.001; adjusted R2 = 0.45). There was a decline in SI of about 41% from the values in young adulthood to those of women in their eighties, about 76.4% of which occurred from age 45-49 years onward. Variation of mean SI with age from the BNR was consistent with the MNR in all but two 5-year age groups. In these two groups (50-54 years, p<0.01; 65-69 years, p<0.05), values derived from the BNR were 5.08% and 5.45% higher than the MNR values, respectively. Comparison of standard deviations in SI with age between the two populations did not show statistically significant differences. Using the fracture risk criteria proposed by the manufacturer, we observed that the MNR was appropriate for skeletal fragility evaluation in Brazilian women. PMID- 11193245 TI - Long-term continuous combined hormone replacement therapy in the prevention of postmenopausal bone loss: a comparison of high- and low-dose estrogen-progestin regimens. AB - We studied the effect of four continuous combined estradiol valerate (E2V) and medroxyprogesterone acetate (MPA) dose combinations in six treatment groups (n = 70 per group) receiving regimens containing 1 mg or 2 mg E2V combined to 2.5 mg or 5 mg MPA, on bone mineral density (BMD) and endometrium in 419 healthy postmenopausal women over 4 treatment years. In two groups the 1 mg dose of E2V was increased to 2 mg after the first 6 months, while the MPA doses remained constant (2.5 mg or 5 mg). The remaining four groups received 1 E2V + 2.5 mg MPA, 1 mg E2V + 5 mg MPA, 2 mg E2V + 2.5 mg MPA, or 2 mg E2V + 5 mg MPA throughout the study. BMD at the spine and hip was measured by dual-energy X-ray absorptiometry and endometrial biopsy samples were taken at 6, 12, 24, 36 and 48 month follow ups. Combinations containing the low dose of 1 mg of E2V (with 2.5 mg or 5 mg MPA) resulted in a mean BMD increase of 6.2% at the spine and 2.9% at the femoral neck after 4 years of treatment. With 2 mg E2V the corresponding increases were 7.4% and 2.9%, respectively. The largest increases in BMD were seen in women for whom the E2V dose was doubled after the initial 6 months of treatment: 8.9% at the spine and 4.2% in the femoral neck. Both MPA doses (2.5 mg and 5 mg) effectively prevented estrogen-induced stimulation of the endometrium. No endometrial hyperplasia was observed in any of the treatment groups. Lower-dose combinations of continuous combined estrogen-progestin regimens are effective in increasing and maintaining BMD and provide a good endometrial safety profile for the long-term prevention of osteoporosis in postmenopausal women. PMID- 11193246 TI - Calcium supplementation with calcium-rich mineral waters: a systematic review and meta-analysis of its bioavailability. AB - The relevance of calcium (Ca2+), an essential bone mineral, to the prevention and treatment of osteoporosis is well established. However, a good deal of evidence casts doubt on the validity of current RDAs (recommended daily allowance), i.e., 800-1000 mg/day. New guidelines consistently advocate higher daily intakes (up to 1500 mg/day), a goal that may be difficult to achieve for many patients. Environmental as well as individual behavioral factors may limit the consumption of dairy products, whereas calcium supplements require a high level of compliance and cause additional costs. Calcium-rich mineral waters may offer a promising alternative. A systematic literature search was performed (Medline, years 1966 1998) to identify experimental studies on the bioavailability of calcium-rich mineral waters. First, all publications on calcium absorption from mineral waters were identified, and, in a second step, studies comparing calcium absorption from mineral waters with that from dairy products. Four studies fulfilled all inclusion criteria. A meta-analysis based on published p values indicated calcium absorption from mineral waters was significantly higher (p = 0.03) than that from dairy products. Although only few studies with a relatively small number of subjects are available to date, the bioavailability of calcium from calcium-rich mineral waters thus seems to be at least comparable to, and possibly better than, that from dairy products. These results are in keeping with the assumption that calcium-rich mineral water is a useful calcium source to achieve new, higher recommended daily allowances of calcium. PMID- 11193247 TI - Relative influence of physical activity, muscle mass and strength on bone density. AB - In a population-based sample of 348 men (age 22-90 years) and 351 women (age 21 93 years), we evaluated the relationship of bone density assessed at a variety of skeletal sites by dual-energy X-ray absorptiometry (DXA) with various muscle mass estimates obtained also from the DXA scan and with physical activity by interview and strength assessed both subjectively and objectively. All these parameters declined with age as judged from these cross-sectional data. All estimates of total skeletal muscle mass were strongly correlated with bone density at different skeletal sites. Muscle mass, in turn, was correlated with physical activity and hand strength. In multivariate models including these variables, muscle mass was the strongest determinant of bone density, accounting for 6-53% (mean 27%) of the variance at the different skeletal sites. Physical activity (and/or a physical activity x age interaction) was an independent predictor of bone mass in 48% of the site-specific models and accounted for 0.03-39% (mean 10%) of the variance, while hand strength (and/or a hand strength x age interaction) accounted for up to 4% (mean 1%) of the variance as an independent predictor of bone density in a third of the models. Although these variables together accounted for a large proportion of the variance in bone density, other potential predictors were not assessed in these analyses. The dramatic decline in physical activity over life seemed unable to completely explain the age-related loss of bone mass, and additional research is needed to determine whether the relationship of muscle mass with bone density is a direct one or due instead to other factors such as circulating hormone levels. PMID- 11193248 TI - Metacarpal morphometry using a semi-automated technique in the assessment of osteoporosis and vertebral fracture risk. AB - Metacarpal morphometry represents a potentially cheap and widely available non invasive assessment of skeletal status. In two cross-sectional studies, we compared the performance characteristics of a semiautomated technique (the Teijin Bonalyzer) with an in-house manual measurement, and with measures of skeletal strength at other sites. The metacarpal cortical index (mCI) was measured on hand radiographs of 178 osteoporotic women using both the Teijin Bonalyzer and a digitizing tablet. Measurements on the latter were consistently lower than with the Bonalyzer except for mCI (0.443+/-0.080 vs 0.364+/-0.060, p<0.001), although correlation coefficients between these two methods were highly significant (r = 0.62-0.83, p<0.001). The reproducibility errors of metacarpal bone mineral density (mBMD) were constant (1.1-1.2%) whilst those for mCI showed a marked operator-dependency (2.0-7.9%). In 379 elderly community-dwelling women, Bonalyzer mCI and mBMD showed a significant decline with age (r = -0.30 and -0.27 respectively, p<0.05). Both mCI and mBMD correlated significantly with forearm BMD (r = 0.50 and 0.57 respectively, p<0.001) and hip BMD (r = 0.48 and 0.53 respectively, p<0.001). After adjustment for age and weight, hip BMD demonstrated the best discrimination for prevalent vertebral fractures as judged by the gradient of risk for a 1 SD decrease in measurement (odds ratio (OR) 2.17, 95% CI 1.56-3.01). Similar but smaller gradients of risk were shown by Bonalyzer mCI (OR 1.32, 95% CI 1.00-1.75), mBMD (OR 1.35, 95% CI 1.02-1.78) and forearm BMD (OR 1.39, 95% CI 1.08-1.80). MCI, and in particular mBMD, may be useful assessments of bone mass and fracture risk. In our study, it is comparable to peripheral assessment of skeletal status by forearm densitometry. PMID- 11193249 TI - A comparison of continuous alendronate, cyclical alendronate and cyclical etidronate with calcitriol in the treatment of postmenopausal vertebral osteoporosis: a randomized controlled trial. AB - A number of drugs are now available for the treatment of established osteoporosis and have been shown to significantly increase bone mineral density (BMD). There are, however, few comparative treatment studies and, furthermore, adverse events remain a problem with some of the newer agents, particularly in the elderly, in everyday clinical practice. We report a 12 month, open labeled, randomized controlled, prospective treatment study in 140 postmenopausal women with established vertebral osteoporosis, comparing the effect of continuous alendronate, cyclical alendronate and cyclical etidronate with calcitriol in terms of gain in BMD, reduction in bone turnover markers and adverse event profile. The mean percentage increases in BMD at 12 months, at the spine and hip respectively, were: continuous alendronate 5.7%, 2.6%; cyclical alendronate 4.1%, 1.6%; cyclical etidronate 4.9%, 2.0% (p<0.0 1) and calcitriol 2.0%, 0.4% (NS). In comparison with calcitriol, the mean changes in BMD at the spine and hip respectively were greater in the other groups; continuous alendronate: 3.7% (95% CI 1.4 to 8.3), 2.2% (95% CI 0.7 to 4.0); cyclical alendronate: 2.1% (95% CI 1.2 to 6.4), 1.2% (95% CI -0.3 to 3.0); cyclical etidronate: 2.9% (95% CI 1.9 to 6.5), 1.6% (95% CI 0.9 to 3.1)). The reduction in bone turnover markers was between 26% and 32% in the alendronate and etidronate groups (p<0.01), with a trend toward greater reduction in the continuous alendronate group. Eight patients discontinued the study: 6 in the continuous alendronate group, 1 in the cyclical alendronate group and 1 in the calcitriol group. Two patients in the cyclical etidronate group were unable to tolerate the Cacit component, but continued on substituting Cacit with Calcichew. In summary, 12 months of treatment with continuous alendronate, cyclical alendronate and cyclical etidronate are effective in terms of the gain in BMD at the anteroposterior spine and total hip in a comparable treatment population. These treatments are more effective than calcitriol and were generally well tolerated. Continuous alendronate showed a trend toward a larger gain in BMD and greater suppression of bone turnover markers than the other treatment groups, but had a higher incidence of adverse events, particularly within the older subgroup. Cyclical alendronate offers a lower adverse event profile and appears to be effective in comparison with continuous treatment, and may possibly be an alternative in the elderly. However, further studies are necessary, but more importantly with fracture end points. PMID- 11193250 TI - Calcaneal ultrasound imaging in healthy children and adolescents: relation of the ultrasound parameters BUA and SOS to age, body weight, height, foot dimensions and pubertal stage. AB - We investigated the quantitative ultrasound (QUS) parameters broadband ultrasound attenuation (BUA) and speed of sound (SOS) measured in the posterior part of the calcaneus at the region of interest (ROI) with the lowest attenuation, using an ultrasound imaging device (UBIS 3000) in 491 healthy Caucasian children and adolescents (262 girls, 229 boys) between 6 and 21 years old. The relation of age, body weight, height, foot dimensions and pubertal stage to BUA and SOS was assessed. BUA increased nonlinearly with age in boys and girls, r2 being 0.44 (p<0.001) and 0.57 (p<0.001), respectively. SOS increased linearly with age in girls (r2 = 0.04, p<0.001). There was no significant increase in SOS in boys (r2 = 0.01, p>0.05). Heel width was significantly correlated with BUA (r = 0.20, p<0.005 in boys; r = 0.27, p<0.05 in girls) and with SOS (r = -0.19, p<0.005 in boys; r = -0.08, p<0.05 in girls). After downward adjustment of the ROI size according to foot length quartiles, significantly lower BUA and SOS values were found compared with those with the standard ROI size of 14 mm. After correction for heel width and adjustment of the ROI size based on foot length, BUA and SOS were significantly associated with age in boys (r2 = 0.36, p<0.001 and 0.06, p<0.05) and in girls (r2 = 0.53 and 0.06, both p<0.001). Tanner stage was significantly correlated with BUA (r = 0.62, p<0.001 in boys; r = 0.73, p<0.001 in girls) but not with SOS. BUA but not SOS increased significantly with the number of years since menarche (p<0.001). In a multiple stepwise regression analysis in boys, age, weight and foot length were independent predictors for BUA, and age and foot length for SOS. In girls, age and weight were independent predictors for BUA and age was the only independent predictor for SOS. After correction for age, pubertal stages and heel width were no longer determinants for QUS parameters in either boys or girls. In conclusion, BUA increased significantly with age in both sexes. SOS increased with age in both boys and girls, but the increase was small and not statistically significant in boys. SOS, as measured with the UBIS 3000 device, may therefore not be appropriate to assess skeletal status in healthy children. Whether SOS and BUA are affected in children with skeletal disorders has yet to be determined. In boys, age, weight and foot length were independent predictors for BUA and age and foot length for SOS. In girls, age and weight were independent predictors for BUA and age was the only independent predictor for SOS. In our opinion, children with small feet should be measured with a smaller ROI diameter than those with larger feet. PMID- 11193251 TI - Effects of body size and skeletal site on the estimated prevalence of osteoporosis in women and men. AB - There is growing awareness that therapeutic decision-making may be confounded by discrepancies in the prevalence of osteoporosis by World Health Organization criteria when bone density is measured at different skeletal sites. To explore this issue, we measured bone density at a variety of skeletal sites in a population-based sample of 348 men (age 22-90 years) and 351 women (age 21-93 years). Men had greater areal bone mineral density (BMD, g/cm2) than women at almost every subregion on total body, anteroposterior (AP) and lateral lumbar spine, proximal femur and forearm scans by dual-energy X-ray absorptiometry. However, adjustment for height or, where possible, calculation of bone mineral apparent density (BMAD, g/cm3) reduced or eliminated these differences. In addition, three different patterns of change in bone density over life were observed at the various skeletal sites as judged from cross-sectional data: no apparent age-related bone loss (e.g., AP spine BMD in men); linear bone loss over life in both sexes beginning in young adulthood (e.g., femoral neck BMD); and bone loss beginning around the time of menopause or a comparable age in men (e.g., midradius BMD). The various adjustments for bone size and the different patterns of age-related change in bone density had profound effects on the estimated prevalence of osteoporosis by World Health Organization criteria, which ranged from 2% to 45% among postmenopausal women and from 0 to 36% among men 50 years of age and older depending upon the skeletal parameter that was assessed. These observations emphasize the difficulties involved in attempts to standardize BMD scores and definitions of osteoporosis for clinical use. PMID- 11193252 TI - Response to the letter by Sanchez concerning Osteoporos Int 1999;10:325-9. PMID- 11193253 TI - [The German Orthopedic History and Research Museum. A museum for research and public health]. AB - The German historical museum of orthopaedic surgery was founded 1959 in Wurzburg. The main task of this institution is the furtherance of science in medical history. Since the beginning, 41 years ago, the number of books and exhibits increased continuously. The library of the museum is the biggest public collection in Germany and contains more then 6000 books and publications in orthopaedics. Furthermore the museum includes a big amount of exoprostheses of the upper and lower limb, alloarthroplasties of hip- and knee-joints, traumatologic implants and instruments of orthopaedic surgery. A big number of bone-preparations with pathologic alterations and variations will also be presented. The exhibition and the library is open to the public and is available to those people in the history of orthopaedic surgery. Local requirements in Wurzburg were one of the reasons to transfer the place of the museum to Frankfurt/Main. The museum was reopened at 6th of June 1998 at the university of Frankfurt/Main, department of orthopaedic surgery. PMID- 11193254 TI - [200 years orthopedics. Images from the past]. AB - The term orthopaedics was first used by a French physician named Nicolas Andry in 1742. Since then the meaning of the term has changed dramatically. Starting as the planned title of a guidebook for parents it developed to become the name of a new medical discipline. During the 19th century orthopaedic surgery was dominated by private institutions, which were a privilege of the wealthy. Orthopaedic surgery as we know it in Germany today developed mostly from the so called "cripple asylums" (Kruppelheime). Their main objective was the treatment of infections of bones and joints, scoliosis and of hereditary diseases. Many of these orthopaedic diseases lost their importance due to prophylaxis and early diagnosis. The great improvements in the living conditions led to a change regarding the age of the patients and the diseases treated. Until world war II mostly children were treated by orthopaedic surgeons. After world war II orthopaedic surgeons have adjusted to the demographic change and have increasingly been treating elder patients. The development and the spread of prostheses display the increasing importance of age related illnesses. PMID- 11193255 TI - [History of artificial limbs for the leg]. AB - Following the development of prosthetics for the lower limb since the middle of the 18th century one will find very interesting similarities to modern prostheses. This becomes evident when looking at former knee and ankle joint mechanisms or socket designs. Also, the materials used for the prostheses underwent very interesting variations. In our paper we will describe the development of socket designs and several materials from the beginning of the 19th century. Several still obtainable books dealing with 200 years of prosthetics development, were reviewed. Charles White describes in the year 1761 a supramalleolar amputation using the flap technique and the specially built BK prostheses the socket. V. Brunninghausen describes in 1809 a socket made of tin sheet. It was built oval, as the normal transverse section of the thigh is. Stump adhesion was obtained when a shortly trimmed dog fur--panelling the socket and covering the stump--was attached like brushes end on end. A similar fitting was described by Heine in 1811, v. Dornbluth in 1831, and Mrs. Eichler in 1836. Hermann first mentioned the need of a perpendicular construction of prostheses. Parmelee developed in 1868 the first suction socket. The first tuber-enclosing socketdesign was made by Riedel in 1911. We will show documents from this time and will also show, that muscle-physiological aspects had a very important influence on socket designs. PMID- 11193256 TI - [From sciatica to intervertebral disk displacement. On the history of a disease concept]. AB - Since antiquity low back pain spreading down to the buttock and the leg with or without neurological symptoms has repeatedly been described by medical authorities. To extract well defined nosological entities out of the medley of "sciatica" was a demanding process within a labyrinth of often misleading clues. Although the herniated intervertebral disk was recognised about the middle of the 19th century the causal nexus between intervertebral disk displacement and sciatica was only demonstrated in the thirties of the 20th century. The critical appraisal of pathomorphological lesions in patients suffering from sciatica was, as it still is, a challenging task even for experienced physicians. Key texts and their authors recall the main steps towards our modern concept of lumbar intervertebral disk displacement to the readers mind. PMID- 11193257 TI - [History of meniscus surgery. From excision of joint loose bodies to meniscus suture]. AB - In comparison with other operative procedures, the history of meniscal-surgery offers some particular differences. Over a long period of time injuries of the semilunar-cartilages of the knee-joint were not generally recognised. In the 18th century only was the clinical picture roughly outlined. There is evidence, that parts of the meniscus were removed much earlier than we have historic proof of. These meniscal fragments were generally mistaken for "loose bodies" in the joints, not knowing the exact etiology. Operative interference with joints was afflicted with a very high incidence of infections and thus complications. Due to this reliable standards of sterility were imperative to obtain reproductive and satisfactory results in surgery of the knee-joint and this is why the discovery and implementation of antiseptic and aseptic principles play such an important role in joint- and, in particular, in meniscal-surgery. The development of meniscal-surgery is dominated by a lengthy discussion about the way in which the injuries of the semilunar cartilages should be dealt with operatively. Fundamental techniques such as fixation of the cartilage by sutures, limited or total removal of the meniscus were established as early as 1895. Over a long period they existed concurrently and their adequate application remained cause for a highly controversial discussion until the end of the 20th century. Not before more detailed knowledge was gained about the exact morphology of the meniscus and the rising of arthroscopic surgery offered new surgical perspectives, it was possible to establish a widely accepted standard of meniscal surgery. PMID- 11193258 TI - [History of 1906 census of handicapped patients]. AB - The census of cripples ("Reichskruppelzahlung") in the German Reich plays a central role in the development of orthopaedic surgery. Local censuses conducted by protestant ministers had already pointed out the great number of disabled children without appropriate care. It was the achievement of Konrad Biesalski, who was an orthopaedic surgeon, and of Eduard Dietrich, a Prussian government official, that a nation-wide census for disabled people was conducted. The concerns of the Reich-health-administration, which had complained about the way the survey was to be made, were neglected. These concerns were not all unjustified. Both the planning of the census itself and the technical interpretation of the obtained numbers were full of errors. The number of cripples in need of a place in an asylum were very exaggerated. Biesalski is to be held responsible for this systematic error. For him the census was only a way to influence the public opinion and had no scientific value. The public was worried by the great numbers of cripples in need of medical care and the foundation of asylums for cripples was added to the social political agenda. Along with these asylums came the promotion of orthopaedic surgery. The law, which laid the foundation for these institutions, the "law for the welfare of the cripples in Prussia" of 1920, would have never been passed, if it had not been for Biesalski's manipulated numbers. One can say that the artificially inflated numbers of the "Reichskruppelzahlung" were a lie for a good cause. PMID- 11193259 TI - [Historical aspects of joint prosthesis implantation. A bibliographic study]. AB - Joint replacements are frequent and effective. The results are generally very positive. It is important to understand former techniques and the historical development of artificial joints by reviewing the bibliographical sources. This article provides a thorough synopsis of former efforts to fully appreciate present-day successes. PMID- 11193260 TI - [Changes in the concept of fracture healing and callus formation]. AB - Although the treatment of fractures has repeatedly been documented throughout history, little attention has been paid to the historical development of the understanding of fracture healing and callus formation in itself. In antiquity, the capability of bone to regenerate was doubted, and Galen attributed the consolidation of a bone fracture to a sap (succus ossificus) that came from the food ingested. Later, in the eighteenth century, a haughty debate broke out as to the seat of the organ that controlled the by now accepted process of new bone formation. While Duhamel du Monceau (1700-1781) believed the periosteum was responsible for the callus formation--this idea being based on his observations of trees--Albrecht von Haller (1708-1777) and his scholars and disciples ascribed this function to the succus ossificus and to the bone marrow. The studies on experimental fracture healing that began during the seventeenth century resulted in the eighteenth-century discovery of the complex processes involved in the formation of callus with the aid of madder staining. The conciliation of the two major schools of thought was finally brought about when in the nineteenth century both periosteal and endosteal callus formation were shown to occur. The anatomical reposition of the fractured components and the stable fixation through osteosynthesis led to a novelty of the twentieth century: callus-free healing of bone fractures. Based on key texts and their authors, the zigzag course taken by our understanding of bone fracture healing and callus formation is illustrated. PMID- 11193261 TI - [Effects of early estrogen replacement therapy on bone stability of ovariectomized rats. A biomechanical and radiologic study of the tibial plateau]. AB - Postmenopausal osteoporosis leads to a significant increase in bone fragility. In this study we used the rat tibia plateau fracture model to investigate the efficiency of estrogen replacement therapy (ERT) to mitigate the post-ovariectomy decrease in fracture load. A total of 73 virgin Sprague Dawley rats had been ovariectomized and 26 animals underwent sham operation. The ovariectomized animals were either untreated (n = 35) or treated with estrogen injections (10 micrograms/kg per day 3 days a week until sacrifice), starting treatment at either 0, 5, 8, or 13 days post surgery. Before starting ERT and at 50 days post surgery, the trabecular structure of the right proximal tibial metaphysis of each animal was imaged non-invasively using high resolution X-ray topography. The animals were then sacrificed and the right knee from each animal was harvested and mounted into a servo-hydraulic materials testing system so that the distal femoral condyle could be forced into the proximal tibial plateau until fracture occurred. The failure load (F) of the ovariectomized group without estrogen administration was significantly less than that for the sham group. The mean stiffness (K) of the ovariectomized group was 22 percent less than that of the sham group, though this difference did not reach statistical significance. Across all groups, the failure load and stiffness were significantly correlated with the trabecular bone volume. Our data suggest that prompt ERT can increase the fracture load and stiffness of trabecular bone by allowing bone formation to continue in previously activated bone remodeling units while suppressing the production of new remodeling units. This may be the mechanism by which estrogen and other antiresorptive agents increase bone mass, and thereby reduce the risk of osteoporotic fractures in postmenopausal women. PMID- 11193262 TI - [It is worthwhile exploring the roots!]. PMID- 11193263 TI - As simple as possible, but not simpler. PMID- 11193264 TI - End-tidal CO2: physiology in pursuit of clinical applications. PMID- 11193265 TI - Treatment of stroke on an intensive stroke unit: a novel concept. AB - In industrialised nations stroke ranks as number three among causes of death and is the most frequent cause of disability in old age. Demographic changes will result in stroke gaining increasing importance for individuals as well as for society as a whole. Stroke is already a major cost factor for healthcare and social security systems because of its high long-term costs. Therapeutic nihilism, although still widespread among patients and some physicians, is no longer justified. Long-term outcome after stroke can be significantly improved by providing therapy in wards specialised in early rehabilitation, so-called 'stroke units'. Recent magnetic resonance imaging (MRI) and positron emission tomography (PET) studies, as well as lysis therapy studies have shown that the first 3-6 h are crucially important. For this reason, the concept of "intensive stroke units" also called "intensive care stroke units" has been implemented in Germany. The goal of an intensive stroke unit is the optimal care of stroke patients under intensive care conditions for the first 3-4 days with the aim of improving outcome, long-term morbidity, and reducing long-term healthcare costs. Another important objective is the development and research of new therapeutic concepts and approaches that are based on pathophysiological considerations. A further goal is the initiation of specific therapies depending on the suspected underlying pathophysiology, for example, local or systemic thrombolysis, full dose heparinisation, platelet aggregation inhibitors, oral anticoagulants, neuroprotective agents, decompression craniotomy, sympathomimetically supported volume therapy and hypothermia. A final objective is to minimise the number of complications through intensive monitoring. Basic acute management includes optimal oxygen supply, rapid normalisation of blood glucose and body temperature, volume therapy, maintaining a high blood pressure and cardiac output to improve remaining cerebral perfusion in the presence of ischaemically impaired autoregulation, treating cerebral oedema, prophylaxis of thrombosis, and early mobilisation. Rapid and easy access to computerised tomography (CT), MRI, Doppler and duplex scanning of the brain-supplying blood vessels, and echocardiography is essential. The ready availability of intensive care monitoring (blood pressure, electrocardiography, central venous pressure, transcranial Doppler (TCD), TCD embolism detection, cerebral pressure, electroencephalography and cardiac output is also imperative. We would like to stress at this point that this manuscript is a personal view describing stroke care in Germany. Many of the principles described have not been widely adopted elsewhere, perhaps in part due to a lack of available facilities. However, many of our recommendations are based on logical principles and thus, we feel, bear further scrutiny. PMID- 11193266 TI - Expiratory time constants in mechanically ventilated patients with and without COPD. AB - OBJECTIVE: In mechanically ventilated patients, the expiratory time constant provides information about the respiratory mechanics and the actual time needed for complete expiration. As an easy method to determine the time constant, the ratio of exhaled tidal volume to peak expiratory flow has been proposed. This assumes a single compartment model for the whole expiration. Since the latter has to be questioned in patients with chronic obstructive pulmonary disease (COPD), we compared time constants calculated from various parts of expiration and related these to time constants assessed with the interrupter method. DESIGN: Prospective study. SETTING: A medical intensive care unit in a university hospital. PATIENTS: Thirty-eight patients (18 severe COPD, eight mild COPD, 12 other pathologies) were studied during mechanical ventilation under sedation and paralysis. MEASUREMENTS AND RESULTS: Time constants determined from flow-volume curves at 100%, the last 75, 50, and 25% of expired tidal volume, were compared to time constants obtained from interrupter measurements. Furthermore, the time constants were related to the actual time needed for complete expiration and to the patient's pulmonary condition. The time constant determined from the last 75% of the expiratory flow-volume curve (RCfv75) was in closest agreement with the time constant obtained from the interrupter measurement, gave an accurate estimation of the actual time needed for complete expiration, and was discriminative for the severity of COPD. CONCLUSIONS: In mechanically ventilated patients with and without COPD, a time constant can well be calculated from the expiratory flow-volume curve for the last 75% of tidal volume, gives a good estimation of respiratory mechanics, and is easy to obtain at the bedside. PMID- 11193267 TI - End-tidal CO2 pressure determinants during hemorrhagic shock. AB - OBJECTIVES: To examine the relationship between end-tidal CO2 (PETCO2) and its physiological determinants, pulmonary blood flow (cardiac output, CO) and CO2 production (VCO2), in a model of hemorrhagic shock during fixed minute ventilation. DESIGN AND SETTING: Prospective, observational study in a research laboratory at a university center. SUBJECTS AND INTERVENTIONS: Six anesthetized, intubated, and mechanically ventilated mongrel dogs. Progressive stepwise bleeding. MEASUREMENTS AND RESULTS: We continuously measured PETCO2 with a capnograph, pulmonary artery blood flow with an electromagnetic flow probe, arterial oxygen saturation (SaO2) with a fiberoptic catheter, and oxygen consumption (VO2) and VCO2 by expired gases analysis. Oxygen delivery (DO2) was continuously calculated from pulmonary blood flow and SaO2. We studied the correlation of PETCO2 with CO and VCO2 in each individual experiment. We also calculated the critical point in the relationships PETCO2/ DO2 and VO2/DO2 by the polynomial method. As expected, PETCO2 was correlated with CO. The best fit was logarithmic in all experiments (median r2 = 0.90), showing that PETCO2 decrease is greater in lowest flow states. PETCO2 was correlated with VCO2, but the best fit was linear (median r2 = 0.77). Critical DO2 for PETCO2 and VO2 was 8.0 +/- 3.3 and 6.3 +/- 2.5 ml x min(-1) kg(-1), respectively (NS). CONCLUSIONS: Our data reconfirm the relationship between PETCO2 and CO during hemorrhagic shock. The relatively greater decrease in PETCO2 at lowest CO levels could represent diminished CO2 production during the period of VO2 supply dependency. PMID- 11193268 TI - Acute respiratory distress syndrome in trauma patients: ICU mortality and prediction factors. AB - OBJECTIVES: To study the factors that influence the intensive care unit (ICU) mortality of trauma patients who develop acute respiratory distress syndrome (ARDS) and to evaluate determinants of length of ICU stay among these patients. DESIGN: Study on a prospective cohort of 59 trauma patients that developed ARDS. SETTING: ICU of a referral trauma center. Fifty-nine patients were included during the study period from 1994 to 1997. METHODS: The dependent variables studied were the mortality and length of ICU stay. The main independent variables studied included the general severity score APACHE III, the revised trauma and injury severity scores (RTS, ISS), emergency treatment measures, the gas exchange index (PaO2/FIO2) recorded after the onset of ARDS and the development of multiple system organ failure (MSOF). Univariate and multivariate analyses were performed. RESULTS: The mean age of patients was 42.1 +/- 16.7 years, 49 patients (83 %) were male, the mean APACHE III score was 52.7 +/- 33.7 points, the ISS 28.5 +/- 11.4 points and the RTS 8.9 +/- 2.5 points. ICU length of stay was 28.5 +/- 24.5 days and the mortality rate 31.7 % (19 deaths). Mortality was associated with the following: PaO2/FIO2 ratio on the 3rd, 5th and 7th days post-ARDS; high volume of crystalloid/colloid infusion during resuscitation; the APACHE III score; and the development of MSOF According to the multivariate analysis, the mortality of these patients was correlated with the PaO2/FIO2 ratio on the 3rd day of ARDS, the APACHE III score and the development of MSOF. This analysis also showed days on mechanical ventilation to be the only variable that predicted ICU length of stay. CONCLUSIONS: The ICU mortality of trauma patients with ARDS is related to the APACHE III score, the gas exchange evolution as measured by the PaO2/FIO2 on the 3rd day and the progressive complications indicated by the onset of MSOF. The length of ICU stay of these patients is related to the number of days on mechanical ventilation. PMID- 11193269 TI - High survival in adult patients with acute respiratory distress syndrome treated by extracorporeal membrane oxygenation, minimal sedation, and pressure supported ventilation. AB - OBJECTIVES: To evaluate the results of treatment of severe acute respiratory distress syndrome (ARDS) with extracorporeal membrane oxygenation (ECMO), minimal sedation, and pressure supported ventilation. DESIGN AND SETTING: Observational study in a tertiary referral center, Intensive Care Unit, Astrid Lindgren Children's Hospital at Karolinska Hospital, Stockholm, Sweden. SUBJECTS AND METHODS: Seventeen adult patients with ARDS were treated with venovenous or venoarterial ECMO after failure of conventional therapy. The Murray score of pulmonary injury averaged 3.5 (3.0-4.0) and the mean PaO2/FIO2 ratio was 46 (31 65). A standard ECMO circuit with nonheparinized surfaces was used. The patients were minimally sedated and received pressure-supported ventilation. High inspiratory pressures were avoided and arterial saturation as low as 70% was accepted on venovenous bypass. RESULTS: In one patient a stable bypass could not be established. Among the remaining 16 patients 13 survived (total survival rate 76%) after 3-52 days (mean 15) on bypass. Major surgical procedures were performed in several patients. The cause of death in the three nonsurvivors was intracranial complications leading to total cerebral infarction. CONCLUSION: A high survival rate can be obtained in adult patients with severe ARDS using ECMO and pressure-supported ventilation with minimal sedation. Surgical complications are amenable to surgical treatment during ECMO. Bleeding problems can generally be controlled but require immediate and aggressive approach. It is difficult or impossible to decide when a lung disease is irreversible, and prolonged ECMO treatment may be successful even in the absence of any detectable lung function. PMID- 11193270 TI - Effect of epidural blockade on indicators of splanchnic perfusion and gut function in critically ill patients with peritonitis: a randomised comparison of epidural bupivacaine with systemic morphine. AB - OBJECTIVES: (a) To measure gastric tonometry values in critically ill patients with peritonitis and to assess the impact of epidural analgesia on these values. (b) To assess the impact of epidural analgesia on gastro-intestinal motility by abdominal ultrasound and paracetamol absorption. (c) To observe any change in clinical outcome that may result from the use of epidural analgesia in such patients. DESIGN: A double-blinded, prospective, randomised and controlled study of general intensive therapy unit (ITU) patients. PATIENTS: Twenty-one patients admitted with peritonitis and adynamic small bowel following abdominal surgery were randomly allocated to receive either intravenous morphine or epidural bupivacaine for analgesia. MEASUREMENTS AND RESULTS: Gastric intramucosal pH (pHig) and the mucosal:arterial PCO2 gradient (Pg-PaCO2) were measured at admission and after 24 h of analgesia. Analysis of mean changes in tonometry values showed a rise in Pg-PaCO2 and a fall in pHig in the morphine group and a significant difference between groups in the Pg-PaCO2 trends (p = 0.024). Significant improvements in the ultrasound appearance of the small bowel were observed in the epidural group (p = 0.0037, Mann-Whitney U test of median changes in a locally developed scoring system). There were no significant differences between the groups in any of the variables derived from the paracetamol absorption test (n = 10); both groups showed persistently delayed gastric outflow throughout the study period. CONCLUSIONS: Epidural analgesia resulted in improvements in gastric mucosal perfusion and the ultrasound appearance of the small bowel, indicating potential clinical benefit in a group of patients in whom epidural catheterisation is traditionally contraindicated. PMID- 11193271 TI - Differential effects of in vitro and in vivo hyperthermia on the production of interleukin-10. AB - OBJECTIVE: To determine whether hyperthermia activates an anti-inflammatory response. DESIGN: A prospective study. SETTING: Heatstroke Center, Makkah, and King Faisal Specialist Hospital, Riyadh, Saudi Arabia. PATIENTS: Twenty-five heatstroke patients pre-cooling (rectal temperature 42.4 +/- 0.8 degrees C) (group 1) and 13 normothermic heat-stressed subjects were studied (group 2). Twelve of the 25 heatstroke patients were also studied post-cooling (group 3). Mononuclear cells from six healthy blood donors resting at 24 degrees C were used for in vitro study. INTERVENTIONS: Mononuclear cells were cultured at a concentration of 1 x 10(6)/ml without and with lipopolysaccharide (LPS) added at concentration of 10, 100, and 1000 ng/ml. The cells were incubated for 24 h at 37, 39, 41, and 43 degrees C. ELISA was used to measure IL-10 in the supernatant and plasma from heatstroke and heat-stressed subjects. RESULTS: All patients in group 1, 40% of group 2, and 37% of group 3, showed elevation of IL-10 (1289 +/- 2519, 248 +/- 393, and 172 +/- 226 pg/ml, respectively) compared with normal control levels, (< 100 pg/ml) P < 0.05. IL-10 level on admission did not correlate with degree of hyperthermia. During 24 h incubation at 37 degrees C without LPS, no IL-10 was detected, whereas with 10 ng/ml LPS, monocytes released 658 +/- 291 pg IL-10/10(6) cells. At 39 degrees C and 41 degrees C IL-10 release was decreased to 225 +/- 114, and 245 +/- 90 pg/10(6) cells, respectively; and was completely inhibited at 43 degrees C (67 +/- 10 pg/10(6) cells), P < 0.0001. CONCLUSION: Heat-stress with and without hyperthermia is associated with anti inflammatory response in vivo. However, it does not seem to be the direct effect of heat on monocytes, suggesting that other environmental or genetic factors may be involved. PMID- 11193272 TI - Continuous veno-venous hemofiltration without anticoagulation in high-risk patients. AB - OBJECTIVE: To study the safety and operative efficacy of continuous veno-venous hemofiltration (CVVH) without anticoagulation in patients at high risk of bleeding. DESIGN: Prospective cohort study and comparison to control group. SETTING: Tertiary, multidisciplinary intensive care unit. PATIENTS: Forty hemofiltration circuits in 12 patients with severe acute renal failure (ARF) deemed at high risk of bleeding. Forty control circuits in 14 patients treated with low-dose pre-filter heparin infusion. INTERVENTIONS: CVVH at 21/h of pump controlled ultrafiltration without anticoagulation or saline flush in patients at high risk of bleeding. Collection of data at the bedside. MEASUREMENTS AND MAIN RESULTS: Mean circuit life was 32 h (95% CI: 20-44.4) in patients receiving CVVH without anticoagulation. Forty-three per cent of filters lasted longer than 30 h. Circuit lifespan did not correlate with international normalized ratio (INR), activated partial thromboplastin time (APTT) or platelet count. There were no bleeding complications and azotemic control was not compromised by lack of circuit anticoagulation with a mean serum urea of 16.0 mmol/l (95% CI: 14.9-18.1) during treatment. A control group of consecutive similarly ill patients not at high risk of bleeding received low-dose pre-filter heparin (mean dose 716 IU; 95% CI: 647-785). Their mean filter life was 19.5 h (95% CI: 14.2-23.8), significantly shorter than in the study patients (p = 0.017). CONCLUSIONS: Critically ill patients at high risk of bleeding who require continuous renal replacement therapy (CRRT) can be safely managed without circuit anticoagulation. This strategy minimizes bleeding risks and is associated with an acceptable filter life. CRRT without anticoagulation should be strongly considered in high risk patients. PMID- 11193274 TI - Body position does not influence the location of ventilator-induced lung injury. AB - OBJECTIVE: To ascertain whether the locations of ventilator-induced lung injury (VILI) are influenced by body position. DESIGN: Randomized prospective short-term study. SETTING: Animal laboratory at a university school of medicine. INTERVENTIONS: Twelve white rabbits were mechanically ventilated in IMV mode with an infant ventilator (V.I.P. Bird, Bird Products, Palm Springs, Calif., USA). Based on the results of a preliminary study to determine the ventilator settings at which the lungs of rabbits were injured within 5 h in the supine position, the ventilator was set at F(I)O2 0.21, at a rate of 30/min, T(I) 0.6 s, peak inspiratory pressure 30 cm H2O, inspiratory flow 10 l/min with no applied positive end-expiratory pressure (PEEP). Six of the animals were tested in the supine position and the other six in the prone position. Respiratory gases were measured and CT scanning was performed every 30 min. The animals were ventilated for 5 h or until pulmonary parenchymal opacification was detected. The lungs were divided into three areas from apex to base and three levels from ventral to dorsal, and the location of opacification was ascribed according to this scheme. After the experiment, the lungs were excised and examined histologically. MEASUREMENTS AND RESULTS: Parenchymal opacification occurred mainly in the dorsal lung areas. The time from the beginning of ventilation to the appearance of lung damage was 60-120 min in the supine (S) group, and 60-270 min in the prone (P) group, and it was significantly longer in the prone group (P < 0.01). We observed diffuse lung damage, including hyaline membrane formation, intra-alveolar edema, and infiltration of inflammatory cells. CONCLUSIONS: Body position affected the time course of the development of VILI, but it did not affect the location. PMID- 11193273 TI - Contribution of ultrasonography and cholescintigraphy to the diagnosis of acute acalculous cholecystitis in intensive care unit patients. AB - OBJECTIVES: To assess the respective value of ultrasonography (US) and morphine cholescintigraphy (MC) in the diagnosis of acute acalculous cholecystitis (AAC). DESIGN AND SETTING: Prospective study in an intensive care unit of a university hospital. PATIENTS AND INTERVENTION: Twenty-eight patients with clinically and biologically suspected of AAC. US was performed at the bedside and less than 12 h later MC. US was considered positive if three major criteria were present: wall thickness greater than 4 mm, hydrops, sludge; MC results were regarded as positive if the gallbladder could not be visualized. These latter patients underwent cholecystectomy and the diagnosis of AAC was confirmed through histopathological study. MEASUREMENTS AND MAIN RESULTS: Sensitivity of US and MC, respectively, was 50% and 67%, specificity 94% and 100%, positive predictive value 86% and 100%, negative predictive value 71% and 80%, and accuracy 75% and 86%. The correlation between US and MC findings was 71%, with chi = 0.31. By Bayesian analysis the probability of disease if the MC finding was positive was 100% regardless of US results. A positive US finding was associated with a 86% probability of disease, but with a probability of only 66% in case of negative MC results. MC is thus superior to US for confirming AAC in selected critically ill patients. Nevertheless, US is an easy, noninvasive, and effective method of bedside screening. The combination of the two imaging tests improves diagnostic accuracy and reduces false-positive and false-negative rates. Poor agreement between the two tests leads to better diagnostic complementarity. PMID- 11193275 TI - Hemodynamic, biochemical and morphological changes induced by aminoguanidine in normal and septic sheep. AB - OBJECTIVE: To define the acute hemodynamic, metabolic, and morphological changes induced by aminoguanidine, a selective iNOS inhibitor, in septic sheep. DESIGN: Prospective, nonrandomized animal study. SETTING: Animal research facility in a University Hospital. INTERVENTIONS: Adult sheep, sedated and mechanically ventilated, were monitored with a pulmonary arterial catheter and an ultrasonic blood flow probe in the mesenteric artery, to measure the systemic (Q(TOT)I) and the mesenteric (Q(MES)I) blood flow indices, and an ileal tonometer. Four groups of sheep were studied: nonseptic, septic, nonseptic treated with aminoguanidine, and septic treated with aminoguanidine (100 mg kg(-1) h(-1)) (n = 6 for each group). Sepsis was induced by the intravenous administration of E. coli. Hemodynamic and biochemical parameters were measured during 300 min. Histological changes in the liver and small intestinal mucosa were analyzed at the end of the experiment. MEASUREMENTS AND MAIN RESULTS: In nonseptic animals, aminoguanidine slightly increased mean systemic arterial pressure (MAP), decreased Q(TOT)I, and increased vascular resistance index (SVRI) and pulmonary vascular resistance index. Q(MEs)I did not change and Q(MES)I/Q(ToT)I increased. Aminoguanidine also induced intestinal intramucosal hypercarbia, hyperlactatemia, acidemia, hypoglycemia, and morphological signs indicative of tissue ischemia in the small intestinal mucosa. In septic sheep, aminoguanidine increased SVRI and MAP only at 4 h after the septic challenge and thereafter, and worsened gas exchange. CONCLUSIONS: In this model, exogenous administration of aminoguanidine induces beneficial hemodynamic effects 4 h after the septic challenge. In normal animals, however, aminoguanidine was associated with hypoglycemia, acidosis, hyperlactatemia, and intestinal mucosal ischemia. PMID- 11193276 TI - Prostaglandin E1 improves hepatic encephalopathy produced by ischaemia reperfusion liver injury in rats. AB - OBJECTIVE: To investigate the action of prostaglandin E1 on hepatic encephalopathy. DESIGN: Prospective, randomised, controlled animal study. SETTING: University animal laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: After passive avoidance learning, acute liver failure was induced by occlusion of the left portal vein and the hepatic artery for 90 min. Then memory retention was evaluated 48 h later. The effects of prostaglandin E1 on memory retention were examined in animals treated with the agent systemically (intravenous injections with prostaglandin E1 twice before and after surgery, 20 microg/kg each time) and animals treated with the agent topically (intracerebroventricular injection with prostaglandin E1, 0.1 microg/h for 48 h beginning at liver ischaemia). MEASUREMENTS AND RESULTS: Marked damage was found on plasma analysis in animals subjected to liver ischaemia, and the memory retention was also impaired. Intravenous administration of prostaglandin E1 improved both the liver injury and memory retention. However, intracerebroventricular administration of prostaglandin E1 alleviated neither. CONCLUSION: These findings show that prostaglandin E1 contributes to the amelioration of hepatic encephalopathy by improving liver function. PMID- 11193277 TI - The renal and neurohumoral effects of the addition of low-dose dopamine in septic critically ill patients. AB - OBJECTIVES: Dopamine exerts a complicated action on the cardiovascular-renal and neurohumoral systems. We evaluated the effects of the addition of different doses of dopamine on top of treatment with norepinephrine on the haemodynamics, renal function and neurohormones of septic shock patients. DESIGN: Open, uncontrolled, dose-finding study. SUBJECTS: Dopamine was administered, after fluid resuscitation, to septic shock patients who were more than 2 h haemodynamically and pulmonary stable with the use of a constant dose norepinephrine. Patients with a serum creatinine above 180 micromol x l were excluded. METHODS: Dopamine doses of 0, 2, 4, 6 and 0 microg x kg(-1) x min(-1) were given consecutively for 1 h each. Neurohormones were measured hourly after baseline levels had been taken. Systemic haemodynamics were measured using a pulmonary artery (PA) catheter every 30 min, whereas urine collections were examined every hour during the study period. RESULTS AND STATISTICAL ANALYSES: Eight patients (mean age 46 +/- 13 years, M/F 3/5) were included. The median norepinephrine dose at the start of the study was 0.29 microg x kg(-1) x min(-1) (range 0.07-0.48 microg x kg(-1) x min(-1)). Cardiac output (CO) rose during the dopamine infusion for all doses from 7.9 +/- 1.74 l/min to a maximum of 10.1 +/- 1.71 l/min, achieved at the 4 microg x kg(-1) x min(-1) dopamine dose, whereas systemic vascular rate (SVR) decreased slightly for all doses. Heart rate remained unchanged during the 2 microg x kg(-1) x min(-1) dose of dopamine but increased for the 4 and 6 microg x kg(-1) x min(-1) doses from 108 +/- 17 to a maximum of 124 +/- 24 beats/min. Filling pressures remained unchanged whereas the mean arterial blood pressure increased (from 83 +/- 7 to 93 +/- 11 mmHg). Plasma renin activity (PRA) was relatively high (but remained unchanged) as were aldosterone levels. Sodium excretion and diuresis increased for all doses, accompanied by an increase of fractional sodium excretion at the 4 and 6 microg x kg(-1) x min(-1) doses of dopamine. Creatinine clearances remained unchanged. All changed values returned to baseline values after cessation of the dopamine administration. CONCLUSION: During norepinephrine infusion, increasing doses of dopamine from 2 to 6 microg x kg(-1) x min(-1) augments CO, diuresis and sodium excretion in patients treated for septic shock, without changes in creatinine clearance. Higher doses of dopamine (4 and 6 microg x kg(-1) x min(-1)) also induce an increase in heart rate. PRA, aldosterone and norepinephrine levels remain unchanged during dopamine infusion. PMID- 11193278 TI - Possibilities and limits of treatment in patients with thrombotic thrombocytopenic purpura. AB - Results of treatment of 18 patients fulfilling the criteria for TTP are presented. Thrombocytopenia was present in all patients (100%). Sixteen of the 18 patients (88.8%) had mental status changes, and seven of the 18 patients (38.8%) had renal impairment. One patient had a secondary type of TTP, caused by non Hodgkin's lymphoma of the large intestine (that was diagnosed later) and was excluded from the study. Immunosuppresive therapy with steroids, plasma exchange and replacement of removed volume with fresh frozen plasma in a dosage of 25 ml/kg body weight resulted in a statistically significant increase of platelet count (P = 0.00222), and a significant improvement in consciousness defined by increased GCS after 2 weeks (P = 0.00222). In two patients renal function recovered, and in one of them hemodialysis was no longer needed. This improvement in a small group of patients had no statistical significance. TTP recurred in seven patients. High doses of steroids caused serious side effects in two patients: in one patient, steroid diabetes, and in the other one, intestinal perforation. PMID- 11193279 TI - Transfusion requirements during continuous veno-venous haemofiltration: -the importance of filter life. AB - OBJECTIVE: To investigate the relationship between loss of haemofilter circuits due to blood clots and requirement for blood transfusion in intensive care patients. DESIGN: Retrospective case note review. SETTING: A British, nine-bed, tertiary, medical and surgical intensive care unit (ICU) serving a 950-bed university teaching hospital. PATIENTS: Thirty-three ICU patients requiring haemofiltration for more than 48 h. Thirty-three comparison patients requiring 7 or more days of intensive care, without haemofiltration. METHODS: ICU, haemofiltration and haematology records were examined retrospectively. Note was taken of demographic data, daily haemoglobin concentrations and the dates and numbers of blood transfusions and haemofilter clots. RESULTS: The study groups did not differ significantly in terms of age, sex and length of ICU stay. Haemofiltered patients had higher APACHE II scores (21 vs 15, p = 0.006), lower haemoglobin concentrations (102 vs 110 g/l, p = 0.0001) and higher blood transfusion rates (1.1 vs 0.3 units/day, p < 0.0001) when compared to the non haemofiltered group. There was a positive correlation between haemofilter blood clot rate and blood transfusion rate (r = 0.48). More blood was transfused on days when haemofilter blood clots occurred than on days when no haemofilter clot occurred (1.0 vs 0.59 units, p = 0.03). CONCLUSION: Haemofiltration is associated with an increased requirement for transfusion of blood. The temporal relationship between occurrence of haemofilter blood clots and transfusion of blood suggests that haemofilter lifespan may be an important determinant of this. PMID- 11193280 TI - Critical illness onychomadesis. AB - OBJECTIVE: To present our observation of the development of a rare nail deformity in the prolonged course of disease of a critically ill patient with a pulmonary abscess. DESIGN: Case report. SETTING: Tertiary referral, 16-bed, level I surgical ICU in an academic hospital. PATIENT: A 48-year-old Caucasian male was treated with penicillin for a pneumococcal meningitis and pneumonia. He developed a large pulmonary abscess of the right upper lobe and needed prolonged mechanical ventilation. Extensive surgical treatment was successful eventually. A remarkable feature concerned the occurrence of onycholysis of all finger nails and toe nails resulting in complete shedding of the nails (onychomadesis). This phenomenon can be regarded as an extreme manifestation of Beau's lines precipitated by a severe systemic insult. CONCLUSION: We observed the development of onychomadesis in a critically ill patient with a large pulmonary abscess. This association has not been described before. PMID- 11193281 TI - Coagulation inhibitors in sepsis and disseminated intravascular coagulation. AB - Sepsis is a syndrome that is increasing in frequency and continues to be associated with an unacceptably high mortality. DIC is an important and common sequel of sepsis, is implicated in the development of multiple organ failure, and has been shown repeatedly to connote a poor prognosis. Increasing understanding of the pathogenesis of DIC has suggested several novel therapies designed to correct deficiencies in inhibitors of coagulation. To date, small randomized, controlled studies of antithrombin III concentrates in sepsis and DIC have shown a trend to increased survival, but have not achieved statistical significance. Currently, a large randomized controlled trial of antithrombin III in sepsis is being conducted. Until more data are available, important questions remain as to its proper place in the treatment of sepsis, septic shock, and DIC. Similarly, therapy with protein C and tissue factor-pathway inhibitor has been beneficial in animal models of sepsis and DIC. The results of controlled clinical trials in humans are eagerly awaited. PMID- 11193282 TI - Tracheal obstruction caused by minitracheotomy. PMID- 11193283 TI - Visible endotracheal cuff: caution! PMID- 11193284 TI - Multi-organ failure in a patient with sepsis due to Salmonella precipitated by liver trauma. PMID- 11193285 TI - Successful temporary left ventricular assistance with the hemopump assist device during acute myocardial infarction after complex mitral valve surgery. PMID- 11193286 TI - Hypokalemic coma with tetany following pseudo-Bartter syndrome. PMID- 11193287 TI - Hemophagocytic syndrome in the critically ill. PMID- 11193288 TI - Buflomedil poisoning: a potentially life-threatening intoxication. PMID- 11193289 TI - Endogenous endophthalmitis. PMID- 11193290 TI - Shock and other severe manifestations following ethanol-methanol copoisoning. PMID- 11193291 TI - Cold adapted enzymes. AB - The number of reports on enzymes from cold adapted organisms has increased significantly over the past years, and reveals that adaptive strategies for functioning at low temperature varies among enzymes. However, the high catalytic efficiency at low temperature seems, for the majority of cold active enzymes, to be accompanied by a reduced thermal stability. Increased molecular flexibility to compensate for the low working temperature, is therefore still the most dominating theory for cold adaptation, although there also seem to be other adaptive strategies. The number of experimentally determined 3D structures of enzymes possessing cold adaptation features is still limited, and restricts a structural rationalization for cold activity. The present summary of structural characteristics, based on comparative studies on crystal structures (7), homology models (7), and amino acid sequences (24), reveals that there are no common structural feature that can account for the low stability, increased catalytic efficiency, and proposed molecular flexibility. Analysis of structural features that are thought to be important for stability (e.g. intra-molecular hydrogen bonds and ion-pairs, proline-, methionine-, glycine-, or arginine content, surface hydrophilicity, helix stability, core packing), indicates that each cold adapted enzyme or enzyme system use different small selections of structural adjustments for gaining increased molecular flexibility that in turn give rise to increased catalytic efficiency and reduced stability. Nevertheless, there seem to be a clear correlation between cold adaptation and reduced number of interactions between structural domains or subunits. Cold active enzymes also seem, to a large extent, to increase their catalytic activity by optimizing the electrostatics at and around the active site. PMID- 11193292 TI - Telomerase, immortality and cancer. AB - Replication of eukaryotic linear chromosomes is incomplete and leaves terminal gaps. The evolutionary widely distributed solution to this "end replication" is twofold: chromosome ends are capped with telomeres, bearing multiple copies of redundant telomeric sequences, and the telomerase enzyme can add (lost) telomeric repeats. Telomerase in humans, as in all mammals, is ubiquitous in all embryonic tissues. In adults, telomerase remains active in germs cells, and, although down regulated in most somatic tissues, telomerase is active in regenerative tissues and notably, in tumor cells. Telomerase activity is linked to cellular proliferation, and its activation seems to be a mandatory step in carcinogenesis. In contrast to mammals, indeterminately growing multicellular organisms, like fish and crustaceae, maintain unlimited growth potential or 'immortality' in all somatic tissues throughout their entire life. Also this cell immortalization is brought about by maintaining telomerase expression. Disease prognosis for human tumors includes evaluation of cell proliferation, based on the detection of proliferation markers with monoclonal antibodies. The significance of the classical marker Ki-67, and of a novel marker repp-86 are compared with semiquantitative telomerase assays. For tumor therapy, telomerase inhibitors are attractive tools. Results with telomerase knock-out mice have revealed promise, but also risk of this approach. On the other side, telomerase stimulation is attractive for expanding the potential of cellular proliferation in vitro, with possible applications for transplantation of in vitro expanded human cells, for immortalizing primary human cells as improved tissue models, and for the isolation of otherwise intractable products, like genuine human monoclonal antibodies. PMID- 11193293 TI - Molecular diagnostics of infectious diseases: state of the technology. AB - In this review, the basic technologies and procedures currently used in clinical laboratories performing molecular diagnostics are described. Special emphasis on specimen processing has been made since it is one of the most challenging steps involved in molecular testing. Representative examples are given for each type of technology, especially tests that are currently available in the market. The types of hybridization-based and amplification-based procedures are detailed. Finally, current problems and future developments are discussed. PMID- 11193294 TI - Combined chemical-biological treatment of wastewater containing refractory pollutants. AB - Biological processes are usually most efficient for degrading pollutants occurring in wastewater. Refractory and toxic compounds contained limit their applicability. In such cases combinations with chemical oxidation processes may improve the overall efficiency and efficacy. Most suitable oxidation processes for combination with biological treatment are wet air oxidation, ozonation, hydrogen peroxide treatment and other advanced oxidation processes. Most effective are OH-radicals produced in all these oxidation processes. Chemical oxidation produces intermediates with usually improved biodegradability. Process combinations may be serial or with recycling between chemical oxidation and biological treatment. Design criteria, control of combined processes and recent applications are reviewed. PMID- 11193295 TI - Biodegradation of nitroaromatic pollutants: from pathways to remediation. AB - Nitroaromatic compounds are important contaminants of the environment, mainly of anthropogenic origin. They are produced as intermediates and products in the industrial manufacturing of dyes, explosives, pesticides, etc. Their toxicity has been extensively demonstrated in a whole range of living organisms, and nitroaromatic contamination dating from World War II is the proof of the recalcitrance of such compounds to microbial recycling. In spite of this, bacteria have evolved diverse pathways that allow them to mineralize specific nitroaromatic compounds. Degradation sequences initiated by an oxidation, an attack by a hydride ion, or a partial reduction have been documented. Some of these reactions have been exploited in bioreactors. Although pathways and enzymes involved are rather well understood, the molecular basis of these pathways is still currently under investigation. However, productive metabolism is an exception. As a rule, most bacteria are only able to reduce the nitro group into an amino function. This reduction is cometabolic: the metabolism of exogenous carbon sources is required to provide reducing equivalents. Composting and processes in bioreactors have exploited the easy reduction of the nitroaromatic compounds. In the case an amino-aromatic compound is produced, it is important to incorporate it in the remediation scheme. Some processes dealing with both nitro- and amino-aromatic compounds have been described, the amino derivative being either mineralized by the same or, more often, another microorganism, or immobilized on soil particles. Depending on the nitroaromatic compound and the environment it is contaminating, a whole range of reactions and reactor studies are now available to help devise a successful remediation strategy. PMID- 11193296 TI - Prevention of marine biofouling using natural compounds from marine organisms. AB - All surfaces that are submerged in the sea rapidly become covered by a biofilm. This process, called biofouling, has substantial economic consequences. Paints containing tri-butyl-tin (TBT) and copper compounds are used to protect marine structures by reducing biofouling. However, these compounds have damaging effects on the marine environment, as they are not biodegradable. It has been noted that many seaweeds and invertebrates found in the sea are not covered by a mature biofilm. This is due to the release of compounds into the surrounding seawater that deter the settlement of fouling organisms. In addition, seaweeds and invertebrates have bacteria on their surfaces that produce compounds to deter settling organisms. The production of compounds by bacteria and their living hosts work in concert to protect the hosts' surfaces. All of these compounds can be collected so they may be natural alternatives to TBT and copper compounds. However, the benefits associated with the use of bacteria as sources of these compounds means that bacteria are the organisms of choice for obtaining natural products for antifouling coatings. PMID- 11193297 TI - Biotechnological applications of plant freezing associated proteins. AB - Plants use a wide array of proteins to protect themselves against low temperature and freezing conditions. The identification of these freezing tolerance associated proteins and the elucidation of their cryoprotective functions will have important applications in several fields. Genes encoding structural proteins, osmolyte producing enzymes, oxidative stress scavenging enzymes, lipid desaturases and gene regulators have been used to produce transgenic plants. These studies have revealed the potential capacity of different genes to protect against temperature related stresses. In some cases, transgenic plants with significant cold tolerance have been produced. Furthermore, the biochemical characterization of the cold induced antifreeze proteins and dehydrins reveals many applications in the food and the medical industries. These proteins are being considered as food additives to improve the quality and shelf-life of frozen foods, as cryoprotective agents for organ and cell cryopreservation, and as chemical adjuvant in cancer cryosurgery. PMID- 11193298 TI - [A study on parameters to predict tumor volume for stage T1c prostate cancers of Gleason score 6 or less]. AB - The number of cases of stage T1c prostate cancer has dramatically been increasing since the introduction of PSA as a screening test. The patients with T1c prostate cancer are usually treated by radical prostatectomy. In this group, however, some cancers are of small tumor volume and with a Gleason score of less than 7. These cancers are considered to be good candidates for watchful waiting management. We have investigated 40 patients with T1c prostate cancer treated by radical prostatectomy between 1996 and 1998. All 9 patients harboring tumors of Gleason score 7 or greater had tumors larger than 0.5 cm3. We have investigated PSA related parameters including total PSA (PSA), PSA density (PSAD), free PSA, and % free PSA in 31 patients with T1c cancers of Gleason score 6 or less in order to clarify good preoperative predictors of tumor volume. We compared the distribution of PSA, PSAD, free PSA, and % PSA between the larger and smaller tumor groups. There was no significant difference in PSA, PSAD, or free PSA value. The small tumor group had a greater mean % free PSA than the larger tumor group (23.27 versus 11.88, p = 0.007). Areas under receiver operating characteristic curves were 0.715, 0.794, 0.636, and 0.842 for PSA, PSAD, free PSA and % free PSA. In stage T1c prostate cancer of Gleason score 6 or less, % free PSA may be the most useful preoperative predictor for tumor volume of 0.5 cm3 or greater. PMID- 11193299 TI - [A randomized long-term comparative study of clinical efficacy of alpha 1-blocker with or without antiandrogen therapy for benign prostatic hyperplasia: focusing on improvement of I-PSS]. AB - This study was conducted to examine the efficacy of administration of tamsulosin hydrochloride alone or in combination with chlormadinone acetate (CMA) against lower urinary tract symptoms for a period of 52 weeks in 33 patients with benign prostatic hyperplasia. The patients were randomly allocated into a group administered tamsulosin alone and a group administered tamsulosin in combination with CMA. Based on the assessment of the total I-PSS (International Prostate Symptom Score), significant symptomatic improvement was noted 4 weeks after the commencement of drug administration in the tamsulosin + CMA group, whereas no significant improvement was observed in the tamsulosin group. Both irritative and obstructive bladder symptoms improved significantly at any time of assessment after 4 weeks of drug administration in the tamsulosin + CMA group; however, significant improvement was noted only at week 16 and week 52 for irritative symptoms and at week 16 for obstructive symptoms in the tamsulosin group. In particular, obstructive symptoms showed significant improvement at week 4 in the tamsulosin + CMA group, as compared with that in the tamsulosin group. The average value of peak urinary flow rate was significantly increased in the tamsulosin + CMA group (10.4 ml/s to 15.6 ml/s) as compared with that in the tamsulosin group (8.5 ml/s to 10.5 ml/s). These findings indicate that combined administration of tamsulosin and CMA resulted in early improvement of lower urinary tract symptoms in these patients. Long-term combined administration of tamsulosin and CMA thus appears to be a promising treatment strategy for the improvement of obstructive symptoms and peak urinary flow rate, particularly, 16 weeks onward after administration in patients with benign prostatic hyperplasia. PMID- 11193300 TI - [Transurethral microwave thermotherapy for benign prostatic hyperplasia]. AB - The clinical efficacy of transurethral microwave thermotherapy using the PROSTCARE apparatus was evaluated in 60 patients with bladder outlet obstruction associated with benign prostatic hyperplasia. All of the 60 patients received a single thermal session for 60 minutes with an average intraprostatic temperature of 45 degrees C. They were evaluated by analyzing the international prostate symptom score (IPSS), quality of life (QOL) index, maximum urinary flow rate and prostate volume at 2 months after the treatment to estimate criteria for efficacy of treatment in BPH. Both IPSS and QOL index improved significantly. The maximum urinary flow rate improved but there was no significant change. There was no significant change in prostate volume. The rates of improvement in IPSS, QOL index and maximum flow rate were 73%, 78% and 47% of the patients respectively. The rate of overall improvement was 78% of the patients. As a complication after the treatment, 2 patients complained of ejaculation disturbance. PMID- 11193301 TI - [A case of effective endotoxin adsorption therapy for septic shock due to acute pyelonephritis]. AB - Although septic shock has a high mortality rate of 43%, recently the endotoxin adsorption column was established and its efficacy is interesting. We report a very effective case of endotoxin adsorption the rapy for septic shock due to acute pyelonephritis. A 59-year-old man with chief complaints of pyrexia and right backache was referred to our hospital with a small right ureteral stone (4 mm) associated with a low degree of right hydronephrosis. Since it was diagnosed as right acute pyelonephritis, antibiotics were administered; and then septic shock occurred on the day of hospitalization. Endotoxin adsorption therapy was performed for two days and hemodynamic stability was achieved. The concentration of blood endotoxin was reduced remarkably and the efficacy of endotoxin adsorption therapy was suggested. PMID- 11193302 TI - [Brain metastasis of bladder carcinoma after total cystectomy: a case report]. AB - A 74-year-old woman underwent total cystectomy with ureterostomy on March 1993 on a diagnosis of advanced bladder cancer. The pathological diagnosis was transitional carcinoma grade 3, pT3a pN0 pV1, pL2. Two courses of adjuvant chemotherapy with CDDP and MTX were added. Three years and 3 months later, she began to suffer from amnesia and hemiparalysis on her left side. Brain MRI examination revealed a solid tumor, 4 x 4 x 3 cm in size, in the right frontal lobe of the cerebrum. No other metastatic lesions were found. She underwent surgical resection of the tumor and subsequent irradiation to right frontal lobe in the cerebrum. Pathological examination confirmed its origin of bladder cancer. She has been enjoying a disease-free life for 3 years with minimal neurological symptoms. PMID- 11193303 TI - [A case of ileus as a late complication of an ileal conduit in a patient with primary signet ring cell carcinoma of the bladder]. AB - A 69-year-old man visited our hospital with a complaint of dysuria. Intravenous excretory urography, ultrasonography and CT scan showed a tumor at the base of the bladder and the prostate. Transrectal needle biopsy revealed signet ring cell carcinoma. Radical cystectomy and ileal conduit were performed, and a histological diagnosis was a primary signet ring cell carcinoma of the bladder. No recurrence or metastasis was found either on ultrasonography or CT scan at 26 months after the operation. He suddenly suffered from severe abdominal pain, and died of hypovolemic shock by ileus as a late complication of an ileal conduit at 27 months after the operation. An ileus with extensive necrosis of small intestine and cancer recurrence at the junction of the ureter and ileal conduit were observed at autopsy. PMID- 11193304 TI - [Two cases of nephrogenic adenoma in the bladder diverticulum]. AB - We report two cases of a nephrogenic adenoma in the bladder diverticulum. The first patient was an 81-year-old man with gross hematuria. Cystoscopy revealed bladder diverticulum and a papillary tumor within. Bladder diverticulectomy was performed and the histopathological diagnosis was a nephrogenic adenoma. The second patient was a 50-year-old man with gross hematuria and dysuria. Transabdominal ultrasound revealed bladder diverticulum. Transurethral coagulation of the bladder diverticulum was performed. Then three papillary tumors were detected, and were resected transurethrally. The histopathological diagnosis was a nephrogenic adenoma. These are the first and second cases of a nephrogenic adenoma in the bladder diverticulum reported in Japan. PMID- 11193305 TI - [Clinical experiences of endotoxin removal columns in septic shock due to urosepsis: report of three cases]. AB - Clinical experiences of endotoxin removal using polymyxin B immobilized fiber column (PMX) in three septic shock patients are reported. The patients were referred to our hospital with complaints of high fever and severe pain during urination. Physical examination and laboratory data revealed severe hypotension, tachycardia, and pyuria. Diagnoses of septic shock due to urosepsis were made. After antibiotic therapy and anti-shock therapy, direct hemoperfusion using polymyxin B immobilized fiber column (PMX) was carried out. Thereafter, cardiovascular instabilities were improved without increasing the supply of catecholamines. PMX therapy for systemic inflammatory response due to infection was effective in treatment of cardiovascular instabilities. PMID- 11193306 TI - [Intra-arterial infusion chemotherapy for liver metastases of testicular tumors: report of two cases]. AB - Two cases of testicular tumors with lymph node involvement and multiple lung and liver metastases were treated successfully with intra-arterial infusion chemotherapy. Case 1: A 30-year-old man presented with right scrotal swelling and an abdominal mass. He had a large retroperitoneal mass and multiple lung and liver metastases on computed tomographic (CT) scan and chest X-ray. Right inguinal orchiectomy was performed. Histopathological diagnosis revealed embryonal cell carcinoma and choriocarcinoma. Cisplatin, vinblastine, VP-16 and pepleomycin combination chemotherapy (PVeBV) was started and repeated for 2 courses. The retroperitoneal mass and lung tumors decreased in size, but liver tumors enlarged. Systemic and intrahepatic arterial infusion combined with chemotherapy was administered, and intra-arterial chemotherapy (cisplatin, VP-16) was added. The patient also received systemic chemotherapy (carboplatin, VP-16, ifosfamide). After chemotherapy, retroperitoneal lymph node dissection was performed. Microscopic examination revealed no viable cancer cells. On CT scan, no retroperitoneal, liver, or lung tumor was detected. Case 2: A 43-year-old man presented with right scrotal swelling and an abdominal mass. CT scan revealed a large retroperitoneal mass as well as lung and multiple liver metastases. Right inguinal orchiectomy was performed. Histopathological diagnosis revealed seminoma. Cisplatin, vinblastine, VP-16 and pepleomycin combination chemotherapy (PVeBV) was administered, but the liver tumors ware enlarged on CT scan. Intrahepatic arterial infusion chemotherapy (cisplatin, VP-16) was started and repeated for 4 courses. On CT scan, the lung metastasis seemed to have disappeared, and the retroperitoneal mass and liver metastases were decreased in size. PMID- 11193307 TI - [Burned-out testicular tumor: a case report]. AB - A 29-year-old man was referred to our hospital with loss of appetite and a left lower abdominal mass. A small nodule was palpable in his left testis and ultrasonographic examination demonstrated that the nodule was low echoic. Computed tomography showed a large mass in his left retroperitoneal space. We thought the mass was a metastatic lesion from a testicular tumor. Left orchiectomy was done and microscopic examination revealed no viable tumor cells. Only fibrous tissue, small calcified areas, and hyaline bodies were found. As tumor markers were normalized after 3 courses of chemotherapy with bleomycin, etoposide, and cisplatine, the retroperitoneal mass was removed with the left kidney. It consisted of embryonal carcinoma, mature teratoma, and yolk sac tumor. One course of adjuvant chemotherapy was done and the patient has since been free from recurrence. We suppose that the tumor was a so-called 'burned-out' testicular tumor. PMID- 11193308 TI - [Staging urinary bladder cancer with dynamic MR imaging]. AB - This article reviews the magnetic resonance (MR) staging of bladder cancer. The multiplanar and soft-tissue characterization capabilities of MR imaging make it a valuable diagnostic tool to image the urinary bladder. Recent advances of MR imaging such as fast imaging, pelvic phased array coil, and dynamic imaging improve the image quality and diagnostic accuracy for staging bladder cancer. Some patient-related factors are also important for optimal imaging of the urinary bladder, especially motion artifacts from the gastrointestinal tract and the degree of bladder distension. An anticholinergic agent should be used for suppressing the motion artifacts. Optimal bladder filling can be achieved by asking patients to void and drink water 1 hour before examinations. Scanning perpendicular to the bladder wall is necessary for optimal evaluation for staging bladder cancer. Oblique scanning is needed in cases when a tumor is not located on the dome, base, anterior wall, posterior wall, or lateral walls. The early phase image of dynamic imaging is most useful for staging tumors. Better contrast between tumor and bladder wall on dynamic images provides high staging accuracy, especially in differentiation between superficial tumors and tumors with muscle invasion. MR imaging is comparable to computed tomography (CT) in the evaluation of lymph nodes. Although MR imaging currently is not appropriate for screening for bladder cancer and detecting small tumors, it has been proved to be most useful in the staging of bladder cancer. PMID- 11193309 TI - [Ultrasound in urodynamics]. AB - Recent developments of ultrasound imaging have contributed much to the understanding of urodynamics in patients with lower urinary tract symptoms (LUTS). These include ultrasound estimated bladder weight (UEBW), transrectal power Doppler imaging of the prostate and transrectal ultrasonography during voiding (voiding TRUS). UEBW, which is obtained by measuring the thickness of the anterior bladder wall using a 7.5 MHz probe, represents well the degree of bladder hypertrophy caused by obstruction. This parameter is, accordingly, of clinical use in the evaluation of obstruction. The UEBW predicted the presence of obstruction as determined by pressure-flow study with a diagnostic accuracy of 73%. Transrectal power Doppler imaging of the prostate has made it easy to detect prostatic vessels and furthermore to obtain their resistive index (RI). Accumulating data suggest strongly that RI reflects the intraprostatic pressure. More interestingly, RI decreases significantly during voiding in normal subjects but not in patients with benign prostatic hyperplasia. Thus, this method is of particular use in monitoring noninvasively the dynamic change in intraprostatic pressure during voiding. Voiding TRUS makes it possible to monitor the movement of not only the posterior urethra but also the prostate during voiding. Based on our recent study, the anterior fibromuscular stroma (AFMS) seems to contract to open the urethra. Although the physiological function of the AFMS in the prostate remains unknown, AFMS may play a significant role in normal micturition. Due to its noninvasiveness and ease of application, ultrasound imaging would play a vital role in the diagnostic process for patients with LUTS in future. PMID- 11193310 TI - [Prenatal diagnosis of urological abnormalities]. AB - The frequent discovery of fetal congenital abnormalities has led to a better understanding of pediatric urological disorders. On the other hand, new questions on clinical examinations and management of the children have given rise to much controversy. We reviewed the difficulties and pitfalls surrounding the urological prenatal diagnosis. Accuracy of ultrasonography is operator-dependent, and main factors leading misdiagnosis include oligohydramnios and rare incidence of the abnormalities. Underlying disorders of prenatal hydronephrosis are multifactorial. Efforts to obtain co-existing findings, such as ureteral dilatation or bladder abnormalities, are essential to make accurate diagnosis. Evaluation of fetal renal function is mandatory in critical cases with decreased amniotic fluid volume. Biochemical analysis of fetal urine may be most reliable in differentiating fetuses with a good prognosis from those with a poor prognosis. PMID- 11193312 TI - [Staging and tissue characterization of prostate carcinoma: role of endorectal MR imaging and MR spectroscopy]. AB - The role of magnetic resonance (MR) imaging and MR spectroscopy with an endorectal coil in tissue characterization and local staging was reviewed. Endorectal coil (ERC) MR imaging demonstrated the detailed zonal anatomy of the normal prostate. The sensitivity and specificity of staging prostate cancer for ERC MR imaging was superior to both conventional MR imaging and transrectal ultrasound. ERC MR imaging is the most accurate noninvasive method of staging prostate cancer. However, the accuracy of the diagnosis made by inexperienced radiologists was significantly inferior to that made by experienced radiologists. Endorectal MRI failed to differentiate benign from malignant lesions in some patients demonstrating low signal intensity on T2-weighted imaging in the peripheral zone. MR spectroscopy may provide additional information on tissue characterization, monitoring after treatment and staging. PMID- 11193311 TI - [Evaluation of prostate cancer using FDG-PET]. AB - The clinical usefulness of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) was examined in 54 patients with prostate cancer. FDG accumulation was positive in 38 of 54 the prostates (70%), 3 of 8 the lymph node metastases (38%) and 10 of 16 the bone metastases (63%), which suggested that FDG-PET is not superior to other conventional imaging methods as a tool for tumor detection. On the other hand, a quantitative value for FDG uptake in the prostate, expressed as a standardized uptake value (SUV), significantly correlated to the histological grade, clinical stage and serum PSA of the patients. A decrease of SUV was observed in all the patients who responded to endocrine treatment, and the patients with high pre-treatment SUV were shown to be at the risk for disease progression after initial treatment. The present results indicated that FDG-PET could provide us with useful prognostic information for the patients with prostate cancer by evaluating the malignant potential of the tumor. PMID- 11193313 TI - [Diagnosis of urinary disorders using ultra-thin ultrasound probe]. AB - We have developed a new diagnostic instrument, to visualize small or early lesions from inside by introducing a flexible ultra-thin probe (2 mm in diameter) into the urinary system. The frequency of the oscillator is 20 to 30 MHz, so the tomogram obtained by the method is extremely fine compared with the ultrasonogram obtained by the scanning from outside of the body. Three-dimensional reconstruction of tomogram is also realized. This display method is valuable to plan operations, follow the progress of therapy, and obtain well informed consent from the patient. We are now developing systems to bend and twist the tip of the intraureteral probe. They are applications of shape memory alloy, thermo-electric actuator and magnetic torque. PMID- 11193314 TI - [Usefulness of arousals for the detection of sleep breathing disorder]. AB - Because of the difference of sensitivity among measurement techniques, upper airway obstruction events cannot always be scored as apnea or hypopnea. We hypothesized that arousal accompanied with breathing disturbance is a more sensitive index for the diagnosis of sleep breathing disorders than others. We studied 75 patients with sleep breathing disorder by polysomnograph. Breathing disturbance related arousal (B-Ar) was defined as an arousal accompanied with at least one of the following (apnea, hypopnea, more than 4% oxygen desaturation, snoring), and the breathing disturbance indices were compared. There were close relationships between B-ArI and apnea hypopnea index (AHI), oxygen desaturation index (DI), and percent of total sleep time with SpO2 below 90% in all patients (r = 0.93, r = 0.58, r = 0.92, respectively, all p < 0.001). In 25 patients whose AHI was below 20 per hour, no relationship between B-ArI and AHI was found, and B ArI was significantly greater than AHI. Thus, B-ArI seemed to be more sensitive than AHI. In all 6 patients whose AHI was below 10, B-ArI was lowered decreased by continuous nasal positive airway pressure therapy. These results suggest that B-ArI may be more sensitive in the detection of sleep breathing disorders than the other indices when AHI is below 20 per hour. PMID- 11193315 TI - [A case of idiopathic tracheal stenosis]. AB - A 44-year-old woman who had been treated for bronchial asthma for 5 years was admitted for further evaluation of progressive dyspnea. Physical examination revealed wheezing originating in the neck. A flow-volume curve suggested upper airway stenosis. The patient had no history of trauma, endotracheal intubation, granulomatous diseases, or any other severe respiratory tract infections. Chest radiography and laboratory examination showed no abnormalities. Tracheal X-P, computed tomography and magnetic resonance imaging of the neck, and bronchoscopy demonstrated circumferential subglottic tracheal stenosis extending for 40 mm. The diameter of the lumen was 5 mm at its narrowest. The trachea distal to the lesion was normal. Bronchoscopic biopsy revealed thickened tracheal mucosa and submucosa with increased fibrous tissue and chronic inflammatory cell infiltration, suggesting a nonspecific inflammatory process. These findings are compatible with idiopathic tracheal stenosis, which was reported by Bhalla et al. The patient was treated with Nd-YAG laser surgery via a fiberoptic bronchoscope, which resulted in a great improvement in respiration. Regression of the lesion has not occurred in the 40 months since the laser surgery. The majority of patients with this condition have been treated by surgical resection of the stenotic lesion and reconstruction. However, the success of Nd-YAG laser surgery in the present case suggests that this approach would be a satisfactory alternative procedure for treatment of idiopathic tracheal stenosis. PMID- 11193316 TI - [Acute effects of oxygen on dyspnea and exercise tolerance in patients with pulmonary emphysema with only mild exercise-induced oxyhemoglobin desaturation]. AB - The effects of oxygen on dyspnea and exercise tolerance during a 6-mimute walk test were examined in 10 patients with chronic pulmonary emphysema (CPE) who had only mild hypoxemia at rest (PaO2 > 60 Torr) and mild exercise-induced oxyhemoglobin desaturation (lowest SpO2 > 88%) on compressed air. As a whole, oxygen supplementation (2 l/min) resulted in a 7% increase in the distance walked in 6 min (6 MD), a 3% increase in the lowest SpO2, and an 8% decrease in the dyspnea score. In 6 of 7 patients with severe airflow limitation (one-second forced expiratory volume (FEV1) < 40% of predicted value), 6 MD (7-15%) increased significantly on oxygen, an improvement that correlated significantly with FEV1 (r = -0.65, p < 0.05). These results suggest that supplementary oxygen improves dyspnea and exercise tolerance in CPE patients with only mild exercise-induced hypoxemia despite severe airflow limitation. The long-term efficacy of oxygen in such patients needs further study. PMID- 11193317 TI - [Safety of and untoward reactions to 23-valent pneumococcal vaccine: a prospective study]. AB - The study objective was to demonstrate the safety of Streptococcus pneumoniae vaccine in 430 geriatric patients at high risk of infection. The reactions after inoculation were classified as follows: (1) Grade 1: slight pain at the site of injection; mild systemic fatigue to improve within 3 days. (2) Grade 2: symptoms of swelling, erythema, or pain lasting for more than 3 days; inability to move upper limb due to pain; systemic symptoms such as a temperature above 38 degrees centigrade. (3) Grade 3: reactions requiring immediate medical therapy. Seventy patients (16.3%) showed inoculation reactions, and 360 (83.7%) were asymptomatic. Of the symptomatic reactions, 50 (11.6%) were grade 1.17 (4.0%) grade 2, and 3 (0.7%) grade 3. About 5% of the patients with grade 1 and 2 reactions needed special management. One chronic heart failure patient complained of severe heart failure symptoms after inoculation. PMID- 11193318 TI - [Clinical analysis of patients referred for lung transplantation in eastern Japan]. AB - We investigated the indications for lung transplantation (LTx) in Japan and discussed questions regarding the current Japanese criteria of LTx. This study examined 37 patients referred to our institute for LTx. Among these patients, there were 11 cases of primary pulmonary hypertension (PPH), 6 of lymphoangiomyomatosis (LAM), 4 of Eisenmenger's syndrome, 3 of bronchiolitis obliterans, 2 each of bronchiectasis, idiopathic pulmonary fibrosis (IPF), and pneumoconiosis, and 7 of other diseases. The most frequent age group was 30-39 years (12 cases, 32.4%), and more than half of the patients were female (22 cases, 59.5%). The regions of residence of the patients were Tohoku (19 patients), Kanto (16), and Chubu (2). Patients were referred from all over eastern Japan. On evaluation, LTx was contraindicated in 5 cases, in 4 of which mechanical ventilation had been installed before consultation with us. Six patients died before registration on the Japan Organ Transplant Network (JOT). 6 transplant candidates were registered with JOT, but one (PPH) died after 6 months of waiting, and one (LAM) received a lung transplant from a brain dead cadaver donor. We propose to reform and clarify the Japanese criteria for LTx-both indications and contraindications, to include such indications as a survival probability of less than two years, and such contraindications as mechanical ventilation. Early consultation at LTx centers was hoped for, in accordance with the International Guidelines and a transplant window. PMID- 11193319 TI - [Pulmonary Nocardia otitidiscaviarum infection in an immunocompetent host]. AB - A rare case of pulmonary Nocardia otitidiscaviarum (N. otitidiscaviarum) was encountered in an immunocompetent host. A 74-year-old man was admitted to our hospital with a high fever and a productive cough. His chest radiograph and CT scan revealed infiltrative shadows in the right middle and lower lung fields. Although several antibiotics (third-generation cephalosporin, minocycline, imipenem) were administered, the fever and cough persisted, and C-reactive protein remained elevated. Repeated sputum cultures showed normal flora, so a transbronchial lung biopsy and bronchoalveolar lavage (BAL) were performed bronchoscopically at the right S5. The BAL fluid contained acid-fast, branching filamentous structures. The microorganism was identified as N. otitidiscaviarum by the Research Center for Pathogenic Fungi and Microbial Toxicoses (Chiba University). Trimethoprim-sulfamethoxazole was therefore administered, but the fever continued to rise daily, and C-reactive protein remained elevated. This isolated N. otitidiscaviarum showed resistance to multiple antimicrobial agents in vitro when examined by the disk diffusion method, and so, on the basis of the antibiogram, the patient was treated with clarithromycin (oral, 600 mg/day) plus amikacin (400 mg/day), which proved successful. Testing for pulmonary nocardiosis should be added to the differential diagnosis procedures for refractory pneumonia as an opportunistic infection and for community-acquired pneumonia. PMID- 11193320 TI - [A case of latex allergy with bronchial asthma]. AB - A 26-year-old nurse consulted our department because of shortness of breath, wheezing and skin eruption after eating lunch several days before. At the consultation, the symptoms had disappeared, pulmonary function showed no abnormality, and there were no abnormal findings on chest auscultation. Latex allergy was suspected because of a history of wheezing and skin eruption after wearing latex gloves and an elevated serum IgE level specific to latex antigen. After a usage test of medical latex gloves, wheezing, skin eruption, and a decrease of FEV1.0 on pulmonary function testing were observed. The case was therefore diagnosed as latex allergy with bronchial asthma. Her symptoms were not observed after polymer coated gloves were substituted. Latex allergy is apt to complicate food allergy, an initial symptom of the present case. Specific IgE for several kinds of food was also elevated. PMID- 11193321 TI - [Diagnostic efficacy of 18F-fluorodeoxy glucose-positron emission tomography in multiple solitary pulmonary nodules]. AB - A 73-year-old man was admitted to our hospital for evaluation of abnormal lung shadows in the left lung. Chest computed tomography revealed a cavitary lesion with irregular edges in the right S10 and a nodular lesion with well-defined margins in the left S6. Histological examination of a specimen obtained by transbronchial lung biopsy revealed squamous cell carcinoma in the right S10 but no significant findings in the left S6. Thirdly, 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) demonstrated that the nodular shadow in the left S6 was a low-uptake structure and that the cavitary lesion in the right S10 was a high-uptake lesion. We therefore considered that the nodular shadow in the left S6 was not one of neoplastic disease. Partial lung resection of the left S6 was carried out by videoassisted thoracoscopic surgery. The pathological diagnosis of the left S6 was epithelial granuloma with caseation. A culture of the same resected specimen was positive for Mycobacterium avium. The eventual clinical staging for the squamous cell carcinoma in the right S10 was cT2N0M0 (IB). Radical surgical treatment and right lower lobectomy were performed for the S10 lesion. We considered that 18F-FDG-PET was an effective noninvasive procedure for diagnosis of solitary or multiple solitary nodular shadows in the lung. PMID- 11193322 TI - [Psoas abscess caused by nephrolithiasis with perirenal abscess complicated with pleural effusion]. AB - Left pleural effusion was found in a 60-year-old woman in whom chest radiography performed during a physical check up revealed no abnormality. Abdominal CT scanning revealed an abscess in the left psoas muscle. The psoas abscess was eliminated temporarily by drainage under ultrasonographic guidance and by the administration of antibiotics, but recurred one month later. A stag-horn renal stone considered to have caused the psoas abscess by formation of a perirenal abscess was eliminated by left nephrectomy. It is suggested tentatively that the psoas abscess might have been the cause of the pleural effusion. PMID- 11193323 TI - [A case of colon cancer with tension pneumothorax and empyema as a consequence of colo-pleural fistula]. AB - A 63-year-old man was admitted to our hospital with fever and chest pain. Chest radiography revealed left pleural effusion with left pneumothorax and small nodular shadows in the right lung field. On CT of the chest and abdomen, multiple nodules were seen in both lung fields, and masses appeared in the liver and spleen. Fiberoptic colonoscopy showed obstruction at the end of the transverse colon. Biopsy of this obstruction proved it to be cancer. In this patient, a colo pleural fistula was also diagnosed using thoracoscopy under local anesthesia and from the inflow of contrast medium from the colon into the thoracic cavity seen in abdominal radiographs. This was a rare case of a colo-pleural fistula without diaphragmatic deficiencies. Medical thoracoscopy is useful for the diagnosis of complicated pleural effusions as was seen in this case. PMID- 11193324 TI - [Bronchial atresia with atelectasis of the left upper lobe]. AB - A 69-year-old woman visited her physician on October 1 complain of dry cough. However, the chest radiograph revealed no abnormalities. She was later admitted to our hospital because a radiograph taken by another physician on November 26 revealed a massive lesion in the right upper mediastinum. Computed tomographic findings showed a massive lesion containing a branching structure with a few calcifications, suggesting a case of atelectasis of the left upper lobe with mucus plug. Bronchoscopic examination revealed complete obstruction of the orifice of the left upper lobe bronchus, and so a diagnosis of bronchial atresia was made. However, since the patient had a history of tuberculous peritonitis and the mass lesion was somewhat calcified, the possibility that this was an acquired case could not be ruled out. After treatment with oral antibiotics, the size of the atelectasis was decreased. Therefore, we considered that the expansion of the atelectasis could have been due to superimposed bacterial infection. PMID- 11193325 TI - [A case of pulmonary manifestation associated with myelodysplastic syndrome]. AB - A 69-year-old woman with myelodysplastic syndrome (MDS) was admitted to our hospital because of recurrent fever and pulmonary infiltration shadows. On the seventh day of hospitalization, she had an attack of high fever and cough and laboratory tests revealed an elevated leukocyte count and elevated serum C reactive protein. Chest radiographs showed infiltration shadows in the right middle and lower lung fields. Because a diagnosis of bacterial pneumonia was initially suggested, she was treated with antibiotics. However, the infiltration shadows on the chest radiograph had not improve, so bronchofiberscopy was performed. Analysis of fluid obtained by bronchoalveolar lavage (BAL) showed an increase in the total cell count, predominantly in lymphocytes and neutrophils. A transbronchial biopsy specimen showed infiltration of numerous neutrophils with necrosis under the bronchial epithelium, and edematous septa were infiltrated with numerous neutrophils and lymphocytes. BAL, blood, urine, bone marrow, and sputum cultures were all free of bacteria, mycobacteria and fungi. Interstitial infiltration by numbers of neutrophils associated with MDS was diagnosed and steroid treatment was performed. PMID- 11193326 TI - [A case of primary Sjogren's syndrome with interstitial pneumonia showing bronchiolitis obliterans organizing pneumonia pattern and lymphofollicular formation]. AB - A 46-year-old woman with a 2-year history of xerostomia, who had had an episode of suspected Sjogren's syndrome in 1995, was admitted to our hospital because of a dry cough. Chest radiography on admission showed ground-glass infiltrates and reticular shadows in both lower lung fields. Primary Sjogren's syndrome was diagnosed by lip biopsy. Video-assisted thoracoscopic lung biopsies revealed the co-existence of interstitial pneumonia with the BOOP pattern and follicular bronchiolitis. Treatment with oral prednisolone improved the symptoms, and reduced the abnormal chest shadows. This was an interesting case of the BOOP pattern in a lung lesion associated with primary Sjogren's syndrome. PMID- 11193327 TI - [Dramatic improvement of severe Pneumocystis carinii pneumonia by corticosteroids despite lack of antipneumocystis therapy in acquired immunodeficiency syndrome]. AB - A 30-year-old Thai man was admitted to our hospital complaining of general fatigue, pyrexia, dyspnea, and a productive cough. He was in serious respiratory failure and had a PaO2 of 45.9 Torr in room air. Chest radiography showed marked infiltration of both lungs. Pneumocystis carinii pneumonia (PCP) associated with acquired immunodeficiency syndrome (AIDS) was ruled out by a negative test for HIV antibody. He was given corticosteroids including methylprednisolone mini pulse therapy and antibiotics. This therapy improved his condition and his radiological picture dramatically without antipneumocystis therapy. Bronchoscopy was performed and the transbronchial lung biopsy revealed PCP. On re-examination for HIV-1 antibody, the result was positive. Western blot analysis yielded a definite diagnosis of HIV-1 infection. Our experience strongly supports previous reports that advocated corticosteroids as adjunctive therapy for moderate to severe PCP associated with AIDS and gives us the significance of corticosteroids. PMID- 11193328 TI - [Periodicity in biomacromolecules and creation of artificial proteins from repeats of a microgene]. PMID- 11193329 TI - [Developmental roles of forkhead genes in organogenesis]. PMID- 11193330 TI - [Understanding the enzyme catalysis: the use of multidimensional energy profile]. PMID- 11193331 TI - [Functional analysis of glycolipids in galactosylceramide synthase(CGT)-deficient mice: arrest of male meiosis and compensation of renal function]. PMID- 11193332 TI - [Physiological role of novel metabolic pathway of platelet-activating factor(PAF): PAF-dependent transacetylation]. PMID- 11193333 TI - [The complete genome sequence of Arabidopsis thaliana]. PMID- 11193334 TI - [SWISS-PROT: the curated protein sequence database on Internet]. PMID- 11193335 TI - [Tissue engineering: bioartificial organs for treatment of metabolic diseases]. PMID- 11193336 TI - [Structural analysis of membrane proteins and their charge distribution]. PMID- 11193337 TI - Malignant histiocytosis in cattle. AB - Malignant histiocytosis was diagnosed in 4 cows. In all cases the tumor tissues were composed of cytologically atypical histiocytes with evidence of erythrophagocytosis. The tumor in case 1 appeared highly anaplastic with marked nuclear pleomorphism, and had areas of spindle cell differentiation, but had no relation to malignant fibrous histiocytoma. The neoplastic tissue in case 2, characterized by cohesive growth of tumor cells, was distinguishable from anaplastic carcinoma cells by cytokeratin immunostaining. There were many hemosiderin-laden neoplastic cells suggestive of high phagocytic activity in a lymph node of case 3. The neoplastic cells in case 4, frequently multinucleated, were less atypical than in the other cases. All cases expressed histiocyte associated markers (lysozyme and HAM56), and were negative for cytokeratin, S100, and T- and B-cell lineage-specific markers (CD3 and CD79a). The most frequent HAM56 immunoreactivity was detected in case 4, and the giant, multinucleated forms, reminiscent of epithelioid cell differentiation. seemed not to indicate cytological pleomorphism as a result of neoplastic transformation. PMID- 11193338 TI - Unilateral intrauterine horn insemination of fresh semen in cats. AB - The sperm count required were investigated to obtain a conception rate of 80% by unilateral intrauterine insemination (UIUI) of fresh semen in cats. The conception rates obtained by insemination before and after ovulation were also examined. Thirty-six female cats aged 1-7 years were used in the experiments, and the number of experimental cases was 44. Seven male cats aged 2-12 years from which semen could be collected by the artificial vagina method were used. In artificial insemination, 100 iu x 2 or 250 iu of hCG was administered on days 2-4 of estrus, and sperm were introduced into the uterine horn with a greater number of ovulations (or mature follicles) 15, 20 and 30 hr after hCG administration by laparotomy. The inseminated sperm counts were 2 x 10(6) (Exp. 1). 4 x 10(6) (Exp. 2), and 8 x 10(6) (Exp. 3). As a result, ovulation was induced in 42 of 44 cases (induction rate: 95.5%) regardless of the dosage of hCG. Conception was obtained by UIUI in two of 16 animals (conception rate: 12.5%) in the Exp. 1, five of 16 animals (31.3%) in Exp. 2, and eight of 10 animals (80.0%) in Exp. 3. Regarding the relationship between the ovulation state at insemination and conception, the conception rate obtained by insemination before ovulation was clearly higher than that obtained by insemination after ovulation (p<0.05). Regarding the number of kits compared to the number of ovulations on the inseminated side, the percentages of cases in which the number of kits exceeded the number of ovulations on the inseminated side were similar in all groups inseminated with a different number of sperm. It is therefore necessary to investigate conception rates obtained by bilateral insemination to increase the fertility rate. Based on the above findings, it was shown that the sperm count required for fertilization by UIUI is 8 x 10(6). PMID- 11193339 TI - Unilateral intrauterine horn insemination of frozen semen in cats. AB - Frozen feline semen was prepared using two types of extenders, egg yolk Tris fructose citric acid (EYT-FC) and egg yolk sodium citrate solution (EYC), and the semen qualities after thawing and the conception rates obtained by unilateral intrauterine horn insemination (UIUI) were investigated. Cats used in the experiment were six males and 11 females aged 2-12 years (the number of experimental cases was 17). For preparation of frozen semen, semen collected by the artificial vagina method was adjusted to I x 10(8) sperm/m/ and 7% glycerol, put in 250 microl straws, and then frozen using a cell freezer. The mean sperm motility after thawing was 30.0+/-9.7 (SE) % in the semen prepared with EYT-FC and 30.0+/-3.3% in the semen prepared with EYC. Four of seven animals were fertilized by UIUI using two straws in both extenders, and the conception rate was 57.1%. The mean ratios of number of kits to the number of ovulations in the inseminated side were 61.1+/-24.5% and 30.5+/-3.4% for EYT-FC and EYC, respectively, showing that the ratio tended to be higher in the semen prepared with EYT-FC. The above findings, comparing the two extenders for preparation of frozen feline semen, showed that EYT-FC is slightly superior to EYC. To increase conception and fertility rates, it may be important to increase the sperm count for insemination and to inseminate both uterine horns. PMID- 11193340 TI - Morphological and histochemical changes in the regenerating vomeronasal epithelium. AB - Receptor cell degeneration and regeneration within the vomeronasal organ (VNO) of the rat was studied using both electron microscopy and histochemical methods. Electron microscopy was employed to examine the morphological changes along the surface of the sensory epithelium, and histochemical markers were used to monitor the changes in the epithelial cell layers. Transection of the vomeronasal nerves induced selective degeneration of the receptor cells, and within six days, a significant decrease in the number of receptor cells was observed. During the subsequent stage of receptor cell regeneration, cilia and bud-like structures characteristic of a developing sensory epithelium were seen. By day 15, thin microvilli covering the surface of the receptor cells reappeared in the sensory epithelium. The neural cell adhesion molecule (NCAM) and two vomeronasal system specific lectins; 1) Bandeiraea simplicifolia lectin (BSL-I) and 2) Vicia villosa agglutinin (VVA) were used as the histochemical markers. NCAM immunoreactivity on the surface of the epithelium was observed to be decreased significantly six days after nerve transection, and was restored during receptor cell regeneration (day 15). The reactivity of the two lectins, BSL-I and VVA, was decreased slightly during degeneration, but was still detectable at the time of maximum receptor cell degeneration (day 6). Lectin reactivity was restored to control levels by day 15. These findings suggest that (1) NCAM is a useful marker for vomeronasal receptor cells and that the vomeronasal system-specific lectins may bind to both receptor and supporting cells and (2) degeneration of vomeronasal receptor cells occurs during the first week (day 6) following nerve transection and the receptor cell population begins to recover within 15 days. The morphological changes observed during receptor cell regeneration suggest that the stages of VNO receptor cell regeneration are similar to those observed during development. PMID- 11193341 TI - Reduction in serum lecithin:cholesterol acyltransferase activity prior to the occurrence of ketosis and milk fever in cows. AB - Lecithin:cholesterol acyltransferase (LCAT) is the enzyme responsible for production of cholesteryl esters in plasma. The LCAT activity is reduced in cows with fatty liver developed during the nonlactating stage and those with the fatty liver-related postparturient diseases such as ketosis. The purpose of the present study was to examine whether reduced LCAT activity during the nonlactating stage could be detected before the occurrence of postparturient diseases. Sera from 24 cows were collected at approximately 10-day intervals from -48 to +14 days from parturition. Of the 24 cows, 14 were apparently healthy, whereas 7 had ketosis and 3 had milk fever at around parturition. Of the 14 healthy cows, 7 had unaltered LCAT activity during the observation period, whereas 7 showed reduced activity from -20 to +14 days. Ketosis and milk fever occurred at from -3 to +10 days, but reductions of LCAT activity in diseased cows had already been observed from days -20 to 0. These results suggest that LCAT activity is virtually unaffected during the peripartum period at least in some healthy cows and also that the reduction in LCAT activity can be detected before the occurrence of ketosis and milk fever. PMID- 11193342 TI - Enzyme-linked immunosorbent assays of canine apolipoproteins B-100 and A-I. AB - An enzyme-linked immunosorbent assay (ELISA) for canine blood apolipoprotein (apo) B-100 and A-I was developed. The working range for the assay was 1.8 to 28.7 ng/well for apoB-100 and it was 50 to 410 ng/well for apoA-I. The intra- and inter-assay coefficients of variation for the assay for apoB-100 were 5.4 and 6.9%, respectively, and for apoA-I they were 5.8 and 10.6%, respectively. The average concentrations of apoB-100 and A-I in 25 beagles (males, aged 3-4 years) were 0.084 +/- 0.028 (mean +/- SD) mg/ ml and 6.29 +/- 1.55 mg/ml, respectively. The ratios of canine (C) apoB-100 to CapoA-I were 1.41 +/- 0.58%. The respective concentrations in one case of hyperlipidemia with systemic atherosclerosis were 0.454 mg/ml and 11.28 mg/ml (a ratio of 4.03%). These values were larger than those of the controls. These results suggest that the measurements of CapoB-100 and A-I concentrations by this newly developed ELISA are helpful for diagnosis of lipidosis. PMID- 11193343 TI - Rapid and direct detection of clostridium chauvoei by PCR of the 16S-23S rDNA spacer region and partial 23S rDNA sequences. AB - Clostridium chauvoei causes blackleg, which is difficult to distinguish from the causative clostridia of malignant edema. Therefore, a single-step PCR system was developed for specific detection of C. chauvoei DNA using primers derived from the 16S-23S rDNA spacer region and partial 23S rDNA sequences. The specificity of the single-step PCR system was demonstrated by testing 37 strains of clostridia and 3 strains of other genera. A 509 bp PCR product, which is a C. choauvoei specific PCR product, could be amplified from all of the C. chauvoei strains tested, but not from the other strains. Moreover, this single-step PCR system specifically detected C. chauvoei DNA in samples of muscle from mice 24 hr after inoculation with 100 spores of C. chauvoei, and in clinical materials from a cow affected with blackleg. These results suggest that our single-step PCR system may be useful for direct detection of C. chauvoei in culture and in clinical materials from animals affected with blackleg. PMID- 11193344 TI - Genotyping of feline MHC (FLA) class II DRB by PCR-RFLP method using group specific primers. AB - For genotyping of feline major histocompatibility complex (FLA) class II DRB, the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method using group-specific primers was tried. Sixty-six DRB genes were classified into 8 groups according to differences in the first 5' amino acid sequences. The group-specific primers were designed as forward ones, which were specific for 5' base sequences of genes in each group. Three to 7 appropriate restricted enzymes were selected by computer analysis for RFLP typing of the genes divided into each group. In 6 out of 9 cats, the results of DRB typed by direct sequence method agreed with results of the PCR-RFLP method using group specific primers. In the other 3 cats, the number of genes amplified by group specific primers was I or 2 more than those detected by direct sequence method. The direct sequence method in 9 cats identified 5 new FLA-DRB genes. The PCR-RFLP method using group-specific primers could divide 66 genes into 37 genes and 10 subgroups from the RFLP pattern. One to 6 genes in each cat, and a total of 203 genes and subgroups were detected in 68 domestic cats. The genes detected might be biased to the subgroup G1-1a (28.8%), DRB*0501 (10.3%), G1-2a (9.4%) and G6b (7.4%). The PCR-RFLP method using group-specific primers may be useful in typing FLA class II DRB. PMID- 11193345 TI - Detection of thermophilic Campylobacter from sparrows by multiplex PCR: the role of sparrows as a source of contamination of broilers with Campylobacter. AB - The best combination of primers and the annealing temperature of multiplex PCR for Campylobacter jejuni, Campylobacter coli, and Campylobacter lari were examined. The multiplex PCR was able to detect type strains of the three species. All results of identification of wild strains (30 strains of C. jejuni, 20 strains of C. coli, and 4 strains of C. lari) by the multiplex PCR coincided with those of the conventional biochemical identification tests, suggesting that the multiplex PCR can simultaneously differentiate C. jejuni, C. coli, and C. lari from wild strains of campylobacters easily and rapidly. Campylobacters were detected from sparrow feces by the multiplex PCR and antimicrobial sensitivities of the strains were determined to discuss the role of sparrows in contamination of broilers with C. jejuni. Three out of 13 strains of C. jejuni isolated from sparrow feces showed quinolone resistance. From the frequent use of quinolones for treatment of industrial animals like chickens, pigs, and cows, the three strains of quinolone-resistant C. jejuni in sparrows must have been originated from those industrial animals. Sparrows that have quinolone-resistant C. jejuni were considered to have contacted with industrial animals or thier feed. It may be presumed, on the contrary, that C. jejuni in sparrows could be a potential source of contamination of broilers. PMID- 11193346 TI - Hypercholesterolemia in Shetland sheepdogs. AB - Plasma lipoprotein cholesterol in 64 clinically healthy Shetland sheepdogs was evaluated to assess whether the breed is more susceptible to hypercholesterolemia. The incidence of hypercholesterolemia was clearly higher in Shetland sheepdogs and mean plasma cholesterol level was significantly higher in Shetland sheepdogs than in control dogs. Blood biochemical examinations did not evidence the abnormalities, which imply the causative disorders, and thyroid hormone levels were not significantly different from the controls. These results suggest that the cholesterolemia is a primary disorder. Cholesterol fractionation by agarose gel electrophoresis and ultracentrifugation revealed that accumulation of alpha2-migrating lipoproteins was the common characteristic of dogs showing cholesterol level over 250 mg/dl in the breed. Increase in prebeta-beta lipoproteins was also found in Shetland sheepdogs with marked hypercholesterolemia over 500 mg/dl. Therefore. Shetland sheepdogs may include more dogs with primary disorders in lipoprotein metabolism, which cause hypercholesterolemia. at least in Japan. PMID- 11193347 TI - Differentiation of hamster liver oval cell following Clonorchis sinensis infection. AB - Oval cells which appear in the liver after hepatic injuries are suspected to be progenitor cells for both hepatocytes and bile duct cells. Oval cell isolated from the livers of the hamsters treated with diethylnitrosamine and 2 acetylaminofluorene and infected with Clonorchis sinensis (CS). cultured for 2 weeks and evaluated for differentiation and plasticity by electron microscopy and immunohistochemistry. In the CS-uninfected group, glycogen granules and peroxisomes were noted in the cells that were cultured for 2 weeks. Starting at 1 week postculture, immunoreactivity of the cells to cytokeratin 19 markedly decreased but that to albumin and alpha-fetoprotein gradually increased. This means that oval cells isolated from hamsters that were not infected with CS differentiated toward hepatocyte lineage. However, in the CS-infected group, cultured cells contained numerous rough endoplasmic reticulum and showed immunoreactivity that was generally in reverse to that of CS-uninfected group, meaning that cells isolated following CS infection were primed by CS and differentiated toward bile duct cell lineage. The results of this study suggested that oval cells are indeed bipolar progenitor cells for hepatocytes and bile duct cells and can differentiate toward either lineage depending upon the priming factor. PMID- 11193348 TI - Plasma levels of the chemokine RANTES in macaque monkeys infected with pathogenic and non-pathogenic SIV/HIV-1 chimeric viruses at an early stage of infection. AB - Plasma levels of the chemokine RANTES were examined in monkeys infected with either a pathogenic simian and human immunodeficiency chimeric virus (SHIV) or a non-pathogenic SHIV to determine whether RANTES levels were related to the pathogenicity of the virus, the plasma viral load, or the kinetics of CD4+ T cells. In the results no significant correlation was found between the RANTES kinetics and changes in the CD4+ T-cell numbers nor the plasma viral loads in any of the monkeys, although a transient decrease of the RANTES level was observed in the pathogenic virus-infected monkeys. At least, the plasma RANTES level can not be used as an index of the pathogenicity of the virus at the early stage of infection. PMID- 11193349 TI - The effect of 0.12% unoprostone isopropyl (rescula) on intraocular pressure in normotensive dogs. AB - Rescula (0.12% unoprostone isopropyl) is the first docosanoid compound approved for treatment of glaucoma in humans. It is commercially available in Japan, and is undergoing clinical testing elsewhere. The aim of this study was to evaluate the effect of Rescula on intraocular pressure (IOP) in normotensive dogs. After establishing a baseline diurnal IOP curve, six dogs were unilaterally treated with Rescula while the contralateral eye was treated with a placebo. Applanation tonometry was performed in both eyes, and pupil size was evaluated, 30 min after treatment, and at 1-hr intervals for the next 9 hr. Rescula caused a significant (p=0.014) and long-lasting decrease in IOP, from 20.49+/-2.02 mm Hg in control eyes to 15.49+/-0.69 mm Hg in treated eyes. These results suggest that Rescula is potentially efficacious in treatment of canine glaucoma. PMID- 11193350 TI - Effect of liquid paraffin on antibody responses and local adverse reactions of bivalent oil adjuvanted vaccines containing newcastle disease virus and infectious bronchitis virus. AB - Effects of liquid paraffin on antibody responses and local adverse reactions after intramuscular injection of oil adjuvanted vaccines containing Newcastle disease (ND) and infectious bronchitis (IB) virus were investigated in chickens. Each vaccine was prepared with a liquid paraffin such as Carnation, Crystol 52 and Lytol. These vaccines induced sustained antibody responses against ND and IB. Among local adverse reactions, Lytol induced granulomatous reactions and abscesses, but Carnation and Crystol 52 did not. The residual weight of liquid paraffin at the injection site decreased in the order Carnation, Crystol 52, Lytol. Crystol 52 was composed of relatively few short-chain hydrocarbons (i.e., n-C20H42). The vaccine with liquid paraffin mainly composed of n-C16H34-n-C20H42 was suggested to induce fewer adverse reactions. PMID- 11193351 TI - Three cases of cat scratch disease diagnosed by indirect immunofluorescence antibody assay and/or polymerase chain reaction of 16S rRNA gene of Bartonella henselae. AB - Three suspected cases of cat scratch disease were diagnosed by indirect immunofluorescence antibody assay and/or polymerase chain reaction. Patient 1 was a 10-year-old female who presented swelling of the right axillary [corrected] lymph nodes with pain and fever. She kept a kitten, and many scratches were observed on her both legs and dorsum manus. Antibody titers against Bartonella (B.) henselae were 1:32 for IgM 3 weeks after the onset of the symptoms and 1:64 for IgG 8 weeks after the onset. The DNA for 16S rRNA type I of B. henselae was detected from the blood sample obtained 3 weeks after the onset of symptoms by polymerase chain reaction for the first time in Japan. Patient 2 was a 22-year old female veterinary student with a cat scratch at the bottom of her neck by a male kitten. She developed a papule at the scratch, slight fever, and neck pain. Although both Bartonella-specific IgG and IgM antibodies were negative before the scratch, the IgG antibody titer rose to 1:512 14 weeks after the onset. B. henselae was isolated from the kitten and its DNA found to be for 16S rRNA type I by PCR. Patient 3 was a 23-year-old female veterinary student with a cat scratch on her left forearm. A small reddish papule developed on the scratch, and she experienced swelling of the left axillary [corrected] lymph node and pain. Both the IgG and IgM antibodies against B. henselae were negative before the cat scratch, and the IgG titer rose significantly to 1:128 and 1:1,024 in 2 and 5 weeks, respectively, after the onset of the symptoms. PMID- 11193352 TI - Unique hemagglutination activity of an isolate of Newcastle disease virus. AB - The MET95 strain of a lentogenic Newcastle disease virus (NDV) isolated from a broiler in Japan, showed unique hemagglutination (HA) activity. The MET95 strain failed to show HA when examined by rapid glass plate method although they showed HA titer of 1:1,024 by micro-plate method. This unique HA was also observed after the MET95 strain was passaged ten times in chickens. The failure of HA by rapid glass plate method was not shown in any other NDVs examined. PMID- 11193353 TI - Serological monitoring on layer farms with specific pathogen-free chickens. AB - To monitor the existence of avian pathogens in laying chicken flocks, specific pathogen-free (SPF) chickens were introduced into two layer farms and reared with laying hens for 12 months. SPF chickens were bled several times after their introduction and examined for their sero-conversion to avian pathogens. As a result, antibodies to eight or ten kinds of pathogens were detected in SPF chickens on each farm. Antibodies to infectious bronchitis virus (IBV), avian nephritis virus, Mycoplasma gallisepticum and M. synoviae were detected early within the first month. Antibody titer to IBV suggested that the laying chickens were infected with IBV repeatedly during the experiment on both farms. However, antibodies to infectious bursal disease virus and 6 pathogens were not detected. PMID- 11193354 TI - Prevalence of capsular polysaccharide (CP) types of Staphylococcus aureus isolated from bovine mastitic milk and protection of S. aureus infection in mice with CP vaccine. AB - To determine the prevalence of capsular polysaccharide (CP) types of Staphylococcus aureus isolated from bovine mastitic milk in Korea, the protective effect of the conjugates, composed of microencapsulated S. aureus clinical isolate type 8 CP bound to Pseudomonas aeruginosa exotoxin A (ETA) was evaluated in mice. Of 107 S. aureus isolates, serotype 5 and 8 accounted for only 26 or 24.2%. When serotype 336 antiserum was employed, fifty of the remaining 81 isolates were typed as 336, 26 reacted with two serotypes, and 5 were nontypeable. Mice challenged with the same strain used for immunization had fewer S. aureus cells in their kidneys than mice challenged with the heterologous strain. But the magnitudes of difference on bacterial clearance were similar in both groups, indicating that the significance of this result remains to be determined. Mice immunized with the conjugate elicited an antibody response 3 days post injection, which persisted for 13 days of the observation period after second injection in some mice. The mice immunized with the CP8-ETA conjugates developed antibodies significantly higher than those immunized with CP-Freund's adjuvant or PBS. In in vivo bacterial challenge experiment, the survival rate of mice immunized with CPS-ETA conjugate was significantly higher than that of mice immunized with PBS. It was suggested that CP8-ETA vaccine had a potential to protect mice against experimental S. aureus bacteremia. PMID- 11193356 TI - [Direction of genome-based science]. PMID- 11193355 TI - [Clinical implication of comprehensive geriatric assessment]. PMID- 11193357 TI - [Supplement with target hormone in aged patients with endocrine dysfunction: thyroid hormone replacement therapy]. AB - Hypothyroidism is not rare in aged people. Hashimoto thyroiditis and radiation to the neck region are main causes of hypothyroidism in aged subjects. The symptoms are slowly progressing, and are similar to those of the aged subjects free from thyroid disease. Thus, it is difficult to make a diagnosis of hypo-thyroidism in the elderly. Administration of T4 (not T3) to patients with hypothyroidism completely releases them from symptoms, indicating that supplement with T4 is important in maintaining QOL. However, a risk of acute coronary syndrome is usually associated with the supplement. Rapid decrease in serum levels of TBG is frequently associated with acute coronary syndrome. Slowly increasing the dose of T4 and monitoring serum thyroxine-binding globulin (TBG) and electrocardiogram (ECG) are important during the period of increasing the dose of T4. PMID- 11193358 TI - [Diseases of the biliary tract and pancreas in the aged--results obtained by investigation of the autopsy cases]. AB - Gross and histological examination of the autopsy cases in the aged revealed that: 1. Acute interstitial pancreatitis, which was characterized by rupture of the ducts and ductules associated with profuse intraluminal exudation of polymorphonuclear leucocytes and protein plugs formation, was found in nine cases (0.62%) out of 1457 autopsies. There was scarce parenchymal or fat necrosis which might be caused by impaired secretion by atrophic parenchyma. The interstitial type may represent characteristics of acute pancreatitis in the aged. 2. Pancreatic lithiasis was found in six of 85 cases, or 7.1%. 3. Sites of isolated islets of Langerhans were found in an incidence of 26.5% (53/200), which increased with age. 4. Incidence of endocrine tumors was 10% (6/60) in individuals having histological studies of all sections and 1.6% (12/738) in individuals having histological studies of three random sections of the pancreas. The facts that multiple hormone production was found in as much as 70% and glucagon cells in as much as 85% were characteristics. 5. The atypical epithelia were observed with the highest incidence in the common pancreaticobiliary channel of the papilla of Vater, where carcinoma may arise most frequently. 6. The incidence of cystic lesions increased with age. Small cystic lesions appear to have the potential to progress to malignancy. 7. it may be possible to remove the head of the pancreas while preserving of the vascular arcades and their branches to the duodenum, the bile duct and the papilla of Vater. The artery toward the papilla of Vater is very important for the blood supply of both the papilla and second portion of the duodenum, and should be preserved in duodenum-preserving subtotal resection of the head of the pancreas. Gallbladder carcinoma was found in 94 cases, or 2.1% and gallbladder stone was found in 957 cases, or 21.4% among 4482 cases. Incidence of gallbladder carcinoma was six times higher in the cases with cholecystolithiasis than those without stone. PMID- 11193359 TI - [Treatment of the elderly dementia patients]. PMID- 11193360 TI - [Treatment and care for depression and delusion in late life]. PMID- 11193361 TI - [Problems and strategies in the treatment of mental disorders in elderly patients with physical illness]. AB - There is a high prevalence of mental disorders in the community population of older adults, especially in medical treatment facilities. Therefore, clinicians who treat geriatric patients cannot neglect the psychiatric vulnerability of the elderly population. The fragility of psychological functioning of the elderly is caused not only by psychological contributors, such as various kinds of experiences of loss, but also by biological factors such as decreases in neurotransmitters and in the number of neurons. Another point geriatric clinicians should pay attention to is the powerful mind-body connection in the elderly. Recent psychoneuroimmunological research demonstrates that depression or other types of emotional stress damages the immune system, which can induce some physical diseases. This is especially true for the elderly, who have weakened cell-mediated immune function and are more susceptible to influence by the damaged immune function caused by such psychiatric dysfunction. Also, depression in the elderly can often lead to malnutrition or dehydration, which can induce various kinds of physical illness. On the other hand, physical illness in the elderly can induce depression, because of the psychological vulnerability of the elderly. Due to the strong mind-body connection in the elderly, the availability of psychiatric care is essential. When providing psychiatric care for the elderly, the clinician should attend to all symptoms, not minimizing the importance of biological treatment, while also trying to support the elderly patients psychologically through acceptance of their need for interdependency and respect for their narcissism. PMID- 11193363 TI - [Rehabilitation approaches to CVA in the acute stage]. PMID- 11193362 TI - [The mentally impaired people in old age, care givers, and the society]. PMID- 11193364 TI - [Effects of intensive exercise to facilitate the functional recovery of the hemiplegica due to the stroke]. PMID- 11193365 TI - [Postural and gait instability in patient with Alzheimer's disease]. PMID- 11193366 TI - [Fracture and bedridden in the elderly]. PMID- 11193367 TI - [The relationship between left atrial thrombus and hematological markers in patients with chronic non-rheumatic atrial fibrillation]. AB - We examined the relationship between left atrial thrombus and hematological variables in patients with chronic non-rheumatic atrial fibrillation (NRAf). This study consisted of 122 patients, 76 men and 46 women with a mean age of 73. Transesophageal echocardiography was performed to detect left atrial thrombi, and at the same time hematological variables including hematocrit, platelet count, fibrinogen level, thrombin-antithrombin III complex (TAT), D-dimer (DD) and fibrin degradation product E (FDP-E) levels were measured. Left atrial thrombi were detected in 28 (23%) of the 122 chronic NRAf patients. The serum fibrinogen was significantly higher in thrombus-positive patients than thrombus-negative patients (400 +/- 140 mg/dl vs. 274 +/- 69 mg/dl, p < 0.0001). The patients with left atrial thrombi had significantly higher levels of serum DD (302 +/- 200 vs. 157 +/- 101 ng/ml, p < 0.0001) and FDP-E (169 +/- 129 vs. 85 +/- 68 ng/ml, p < 0.0001) than the patients without. Scoring was made based on the levels of fibrinogen, DD and FDP-E as follows: 0 points if fibrinogen was under 380 mg/dl and 1 points if was 380 mg/dl or over, 0 points if DD was under 150 ng/ml, 1 points if 150 ng/ml or over and under 250 ng/ml, 2 points if 250 ng/ml or over, 0 points if FDP-E was under 70 ng/ml, 1 points if 70 ng/ml or over and under 140 ng/ml, 2 points if 140 ng/ml or over. According to the combined scores for these 3 markers, the prevalence of positive left atrial thrombi was 4% in 46 patients with 0 points, 18% in 38 patients with 1 or 2 points, 38% in 26 patients with 3 or 4 points and 75% in 12 patients with 5 points. PMID- 11193368 TI - [Ability to avoid falls among aged residents in a barrier-free welfare institution]. AB - This study was carried out to investigate the physical functions of the elderly, living in a barrier-free home for the aged and to obtain basic data for giving appropriate guidance on exercise and daily life. A total of 38 women were tested. These included 18 persons (aged 72-87: mean: 80.7) who were living in the home for the aged, and 20 (aged 75-86: mean: 78.3) who voluntarily participated in the "fall prevention school", established in Tokyo Kosei-Nenkin Hospital. The following examinations were done: 1) BMI, Waist/Hip ratio; 2) good walker's index consisting of 10 m walking times, maximum length of steps, and 40 cm-staircase climbing; and 3) equilibrium examination done by gravinography. Statistical analysis was carried out using a paired t-test (p < 0.01). Values for the "good walker's index" were significantly lower in, the "home" group than in the "school" group (p < 0.01). This was especially obvious with 40 cm-staircase climbing. Many of the subjects from the institution group required assistance and there was a significant difference in the chi-squire square distribution between the two groups. Furthermore, on gravinography, the "home" group had significantly inferior values in total length (cm) and Romberg's ratio (p < 0.01). It was clear that residents in the barrier-free home had a significant reduction in good walker's index, indicating an apparent weakening of physical function. PMID- 11193369 TI - [A study of mental health in community-dwelling older persons--influence of cared elderly]. AB - This study aimed to evaluate mental health of elderly persons living in the community and understand the various backgrounds and effects of care giving. The study used a questionnaire from similar to the one used by Matsubayashi et al in the Kahoku-cho study. The Japanese Version of General Health Questionnaire 12 (GHQ-12) was used to evaluate mental health. Responses were received from 2,799 (81.5%) of 3,432 Numura-cho residents (81.5%). After removing inadequate responses, 1,268 (36.9%) (575 men and 693 women) were analyzed. Fifty-five men (9.6%) and 69 women (10.0%) were caring for someone at home. Multiple logistic regression analysis which examined the relation between mental health and the background factors such as having someone to care for, revealed that their mental health was significantly poor compared to those having no one to care for (odds ratio (OR) = 2.01, 95% confidence interval (CI), 1.29-3.15). As for the relation between the degree of care giving and their mental health, the subjective burden was significantly poor at 72-100% (OR = 3.40, 95% CI, 1.71-6.78) and for those with three to eight years of care-giving (OR = 2.22, 95% CI, 1.00-4.90), disabled activity of daily living (almost bed ridden) of the cared for person (OR = 5.53, 95% CI, 2.23-13.7), severely demented state (OR = 5.13, 95% CI, 2.14-12.3), their mental health was significantly poor. However, being able to participate in an event (OR = 0.12, 95% CI, 0.03-0.49) and strong emotional support (OR = 0.12, 95% CI, 0.03-0.49) were negatively associated with caregivers' psychiatric distress. Having someone to care for largely affected mental health of the elderly to subjects living in the community. Services should be devised to serve the needs such as psychological care of care-givers as well as those being cared for. PMID- 11193370 TI - [Relation between hippocampal damage and cerebral cortical function in Alzheimer's disease]. AB - We investigated the relation between hippocampal damage and cerebral cortical dysfunction in Alzheimer's disease (AD) using MRI and SPECT. Nineteen patients with AD and 10 control subjects were studied. Hippocampal damage (including hippocampal formation, entorhinal cortex, and parahippocampal white matter) was assessed to evaluate the severity of atrophy and the magnetization transfer ratio (MTR) and cerebral cortical dysfunction was evaluated by quantitative cerebral blood flow (CBF) measurements using SPECT with 99mTc-ECD. Compared with controls, patients with AD had significantly more atrophy of the medial temporal lobe and a decrease in MTRs of the hippocampus and parahippocampus. There were significant correlations between the severity of hippocampal damage and regional CBF in temporoparietal lobes. Mini-Mental State Examination scores significantly correlated with the severity of hippocampal damage and regional CBFs in temporoparietal lobes. These results suggest that the functional effect of hippocampal damage occurs in temporoparietal lobes in AD, probably due to neuronal disconnections between hippocampal areas (including the entorhinal cortex) and temporoparietal lobes. PMID- 11193371 TI - [Factors influencing continuation of home life after returning home from geriatric intermediate care facilities in a metropolitan suburb]. AB - A follow-up study was conducted to elucidate the factors influencing continuation of home life after returning home from geriatric intermediate care facilities (GICFs). The subjects were 237 elderly persons (56 men, 181 women, average age of 84 years) who were admitted to three GICFs located in the suburbs of Osaka, and their family caregivers. A follow-up study was performed from 1997 to 1998. Seventy percent of the elderly were bedridden persons with grade B or C of activities of daily living (ADL) according to the criteria of disabled elderly of the Japanese government. Dementia was observed in 82.3% of them. Family caregivers were sons (30.7%), daughters (27.4%), daughters-in-law (27.8%) and spouses (9.7%). The percentage of families spending all day long with the elderly person was 57.5%. Although the rate of having their own detached house was high, that of a private room for the elderly individuals was only about 60%. Most of the families cared for the elderly before admission to the GICFs. The families desired them to stay in the GICFs for as long as possible. Therefore, the families did not want to take the elderly into their home after discharge and only 45% of the families desired home care after the discharge. Concerning the flow of the 237 elderly subjects, the rate of admission from hospitals was high (60.8%), and that of discharge to hospitals was also high (44.3%). The place of residence at the end of follow-up was the GICF (35.4%), the elderly subject's home (19.0%), and hospital (16.0%). Of the 96 elderly who had returned home from GICFs, 40.6% were re-admitted to GICFs. According to multiple logistic analysis, the factors related to continuation of home life were "the elderly with family caregivers who can always supervise him/her", and "the elderly without problem behavior". From the results obtained, it is important that in order for disabled elderly individuals to continue their home life, the GICFs must be the function as the center of a comprehensive service system in the community. PMID- 11193372 TI - [Stress management in the workplace in the era of industrial and economic change]. AB - The globalization of the economy and the recent economic recession in Japan has accelerated down-sizing or restructuring of corporations and has resulted in the induction of a wage system according to achievement instead of the traditional seniority wage system, break-down of the life-long employment system, excess labor and increased unemployment. These rapid changes in the labor situation have increased job stress. It was reported in the survey conducted by the Ministry of Labor in 1997 that 62.8 percent of 16,000 workers had anxiety, worry and stress regarding their working life. The need for effective stress management at work has been increasing in this situation, but in the survey mentioned above only 26.5 percent of 12,000 companies replied that they had incorporated mental health measures. The characteristic features of the approaches for stress management in Japan are summarized as follows: 1) The most popular approaches are education and consultation for individual workers. 2) Systematic preventive approaches such as work control, working environment control, organizational change in the health management system, and systematic and continuous educational programs for managers are inadequate. 3) Systems to evaluation the effectiveness of these interventional approaches are also inadequate. Considering the current situation in which there is increasing job stress and a need for the occupational mental health promotion, we propose a series of mini-reviews regarding stress management at work and mention the composition of this series. PMID- 11193373 TI - [Job stress control at workplace: how to plan and conduct]. AB - This review addressed that stress control activities at workplace could be classified into four categories: (1) improvement of work environment; (2) education/training; (3) health care for stress; (4) mental health service. Research has demonstrated that each of these activities is effective to some extent. The review also pointed out that stress control at workplace could be planned and conducted under occupational health systems, e.g., occupational safety & health management system. Then I proposed a possible effective strategy for planning and conducting stress control at workplace. PMID- 11193374 TI - [Role of occupational health staff considered in the case frostbite caused by exposure to liquid chlorine]. PMID- 11193375 TI - [A study on coordination of occupational and community health--a survey of occupational health nurses]. AB - The survey was conducted on occupational health nurses to find out their awareness of the issue, levels of coordination practiced at work and contributing factors. Based on the results, measures to facilitate the coordination of the two areas were examined. The major findings are as follows: 1. Cooperation between occupational and community health nurses: More than 40% of the occupational health nurses surveyed were aware of the necessity for cooperation with community health nurses. However, less than 7% of those surveyed actually practiced it at work. The deciding factors included the use of a support system in the community, previous training in community health, and work experience in health centers in the community. To facilitate the cooperation between the two sectors, it is suggested that occupational health nurses acquire more knowledge of community health issues. 2. Coordination through focusing on the employee's life in the community: More than 85% of those surveyed were aware of the necessity of coordinating occupational and community health issues through focusing on the lives of the employees in the community. However, less than 30% practiced it at work. Awareness and practice of occupational health planning scored the lowest. The deciding factors included completion of a public health nursing course and the number of employees assigned to each nurse, the use of a support system in the community, and previous training in community health. To facilitate coordination of occupational and community health issues, it is suggested that occupational health nurses acquire more knowledge of community health issues, the number of employees assigned be carefully considered, and that activities focusing on community health be incorporated into occupational health planning. PMID- 11193376 TI - [Development of new synthetic method and function of ynolate anions]. AB - Ynolates are carbanions having a triple bond in place of the double bond in enolate anions. Ynolates are ketene anion equivalents, thus ynolates introduce a ketene unit into substrates and the resulting products possess high reactivity. This allows ynolates to undergo unique reaction sequences. For the past 20 years, several methods for the generation of ynolates and their reactions have been developed. Recently, we have developed a novel efficient method for their generation via cleavage of ester dianions. Starting from this success, we have found new reactions of ynolate anions. Ynolate anions react with carbonyl compounds to give beta-lactone enolates, which are converted into olefins with high E-selectivity. It is noteworthy that high E-selectivity was achieved in the synthesis of tetrasubstituted olefins. Utilizing the strong nucleophilicity of the beta-lactone enolates, we have succeeded in the first tandem [2 + 2] cycloaddition-Dieckmann condensation to lead synthetically useful 2,3 disubstituted-2-cycloalkenones in good yields. Ynolate anions were found to react with N-sulfonyl aldimines to give beta-lactams. N-2-methoxyphenyl aldimines efficiently activate their cycloaddition of lithium ynolates via chelation to give beta-lactams and alpha,beta-unsaturated amides. We have demonstrated the high functionality of ynolate anions. Ynolate chemistry has begun and much remains to be discovered. PMID- 11193377 TI - [Research and development of cilostazol: an antiplatelet agent]. AB - In our study, we focused on the fact that platelets play a significant role in thrombus formation in the arterial vessels, and started exploratory research on the antiplatelet agent with a vasodilating action in order to discover a more effective drug for arterial thrombosis. We synthesized many 2(1H)-quinolinone derivatives and evaluated their inhibition of platelet aggregation and their vasodilating activities. First we found cilostamide, which has an amide moiety in the side chain. This compound possessed desired activities, but it caused a side effect of tachycardia, and so, unfortunately, we were unable to pursue its development. After many efforts to modify the side chain moiety to eliminate this side effect, we finally invented cilostazol (OPC-13013), a 2(1H)-quinolinone derivative with a tetrazol ring in the side chain. Cilostazol inhibited human platelet aggregation induced by various stimuli including shear stress in vitro and showed potent antiplatelet effects both in vitro and ex vivo. It was also shown that the drug has antithrombotic effects in experimental thrombus models and a vasodilating activity of the femoral artery and vertebral artery. The mechanism of the action for cilostazol is specific inhibition of cyclic nucleotide phosphodiesterase type 3 (PDE3). Cilostazol was marketed first in Japan in 1988 and later in seven other countries for the treatment of chronic arterial occlusion. It was launched in the U.S. in 1999, and approved in United Kingdom for the treatment of intermittent claudication. More recently, cilostazol was shown to be effective in a clinical prevention study on recurrence of cerebral infarction, and has been applied to the approval of the indication in Japan. PMID- 11193378 TI - [Angiotensin II receptor antagonists: candesartan cilexetil]. AB - Blockade of the action of angiotensin II (AII) has long been a target for the development of novel antihypertensive agents. We recently discovered a novel class of potent nonpeptide AII receptor antagonists, benzimidazole-7-carboxylic acids including candesartan. Candesartan is a highly potent and insurmountable AII type-1 receptor (AT1)-selective antagonist. Structure-activity relationship (SAR) studies revealed that the adjacent arrangement of a lipophilic substituent, a tetrazolylbiphenylmethyl moiety and a carboxyl group was the important structural requirement for potent AII antagonistic activity. Especially, the presence of a carboxyl group at the 7-position was found to be essential for insurmountable antagonism. To improve bioavailability of candesartan, chemical modification was examined to yield candesartan cilexetil, a prodrug of candesartan. Candesartan cilexetil is a potent and long-acting blocker that, when given once a day to patients, provides effective 24 hr blood pressure control. PMID- 11193379 TI - [Modulation of cytokine production from human mononuclear cells by several agents]. AB - We investigated the effects of drugs, especially anti-pulmonary disease agents, on the production of cytokines from human peripheral blood mononuclear cells (PBMC). Roxithromycin (RXM), a macrolide antibiotic with the structure of 14 member macrocycline ring increased adherent cells (monocyte/macrophages), whereas it suppressed the proliferation of PBMC stimulated with phytohemagglutinin (PHA). RXM suppressed the production of IL-1 beta and TNF-alpha from lipopolysaccharide (LPS)-stimulated PBMC in a dose-dependent manner. Levofloxacin, a fluorinated quinolone, increased IL-2 production by PBMC stimulated with PHA. The production of GM-CSF and soluble IL-2 receptor was suppressed at high concentrations of LVFX. LVFX suppressed IL-1 beta production, but did not the production of TNF alpha and IL-8 production. A beta-adrenoceptor agonists (beta-agonist), procaterol, clenbuterol, fenoterol and terbutaline suppressed the production of TNF- and IL-1 beta. TNF-alpha production was almost completely suppressed by dibutyryl cyclic AMP (dbcAMP), whereas IL-1 beta production appeared to be partially refractory even at the highest concentration examined. Both procaterol and theophylline elevated cAMP levels in LPS-stimulated PBMC, but the effect of procaterol was limited. The inhibition of the production of TNF-alpha and IL-1 beta by procaterol was additively potentiated with theophylline. Of examined phosphodiesterase (PDE) isozyme inhibitors type IV PDE inhibitors were more effective in inhibiting the production of TNF-alpha and IL-1 beta by LPS stimulated PBMC than a nonselective, type III or type III/IV inhibitor. The addition of the beta-agonist increased the inhibitory effect of tested PDE inhibitors on the production of TNF-alpha and IL-1 beta Type IV, type III and nonselective PDE inhibitors were effective in inhibiting the production of IFN gamma and IL-2 in a dose-dependent manner. In contrast, the production of IL-4 and IL-5 was inhibited by only the highest concentration of type IV inhibitor, and other agents had no effect on the production. Similarly, dbcAMP inhibited the production of IFN-gamma and IL-2 more potently than that of IL-4 and IL-5. The addition of the beta-agonist increased the inhibitory effect of tested PDE inhibitors on the production of IFN-gamma and IL-2 production. These findings indicate that these agents have an immunodulatory action on the production of cytokines by PBMC and also indicate that they could be potent pharmacological agents for the treatment of diseases in which several cytokines are important etiological factors. PMID- 11193381 TI - [Stereoselective synthesis of cyclopentanones using dirhodium(II)-catalyzed intramolecular C-H insertion reaction]. AB - This review summarizes novel stereoselective syntheses of 3,4-cis- and 3,4-trans 3-alkyl-4-silyloxycyclopentanones using a dirhodium(II)-catalyzed intramolecular C-H insertion reaction as a key reaction. Treatment of diazoketoesters (20a-e) with 1 mol % of dirhodium(II) tetraacetate gave 2,3-trans-3,4-cis-cyclopentanones (21a-e) as major products. The presence of both the keto and ester groups in the precursors was found to be essential for this chemo- and stereoselective intramolecular C-H insertion reaction to take place. A possible interpretation for the observed stereoselectivity is presented. Optically active Corey lactone (38) was synthesized using a similar reaction of chiral alpha-diazo-beta ketoester (33). Next, reactions of 5,6-bisoxygenated diazoketones with Rh2(OAc)4 were investigated. An acetonide derivative (39), upon treatment with Rh2(OAc)4, gave 3,8-dioxabicyclo[3.2.1]octane (42) via oxonium ylide formation/1,2-shift. On the other hand, similar treatment of 5,6-bis(tert-butyldimethylsilyloxy) derivative (47) gave a C-H insertion product (51) which was purified by silica gel column chromatography to give 4-silyloxycyclopentenone (48). Direct reduction of 51 with lithium aluminum hydride gave stereoselectively diol (52) in 52% yield from 47. Reaction of 2-methoxycarbonylcyclopentenone (48) and a 2-benzenesulfonyl congener (50) with R2CuLi or RMgBr-CuI stereoselectively gave 2,3-trans-3,4-trans cyclopentanones (22, 57) as a major diastereoisomer. On the other hand, reaction with R3 Al in toluene exclusively gave the corresponding 3,4-cis-adducts (21 and 58). PMID- 11193380 TI - [Molecular neuropharmacology of nociceptive transmission and opioid receptors]. AB - This review summarizes our studies using pharmacological, neurochemical and molecular biological methods on the nociception in the CNS and opioid receptors (OPRs). We designed an in vitro fluorometric on-line monitoring system including an immobilized glutamate dehydrogenase column, and for the first time actually demonstrated that capsaicin induced the release of glutamate from rat dorsal horn slices containing the terminal area of primary afferents, in concentration dependent, extracellular Ca(2+)-dependent and tetrodotoxin-resistant manners. Further, such a release was shown to be inhibited through mu- and delta-opioid receptors and alpha 2-adrenoceptors. On the other hand, we found that intracerebroventricular injections of interleukin (IL)-1 beta in rats produced biphasic effects on the mechanical nociception in rats (hyperalgesia in lower concentrations but analgesia in higher ones) and that similar injections of cytokine-induced neutrophil chemoattractant-1 (CINC-1) facilitated mechanical nociception in rats. The above described facts suggest that glutamate and some sorts of cytokines (IL-1 beta and CINC-1) contribute to nociception at least from the primary afferents to the spinal dorsal horn neurons and in higher brain, respectively. We have cloned rat kappa- and mu-opioid receptors. Using cloned cDNA for OPRs, we demonstrated (1) the distribution of mRNAs for OPRs in the rat central nervous system, (2) coexistence of each type of mRNA for mu-, delta- and kappa-OPRs and pre-protachykinin A mRNA in the dorsal root ganglion neurons, (3) an increased expression of mu- and kappa-OPR mRNAs in the I-II layers of rat lumbar dorsal horn with an adjuvant arthritis in the hind limb, (4) the inhibitions of N- and Q-types of Ca2+ channels by mu- and kappa-OPR agonists and (5) cross-desensitization of the inhibition through a common intracellular phosphorylation-independent mechanism, (6) pharmacological characterization of "antagonist analgesics" as partial agonists at every type of OPRs, and (7) the key-structure(s) of OPRs for discriminative binding of DAMGO to mu-OPR. PMID- 11193382 TI - [Efficient chiral control based on five-membered heterocyclic and related systems]. AB - The synthetic potential of some simple five-membered heterocycles, including 2 oxazolone, 1,3-dihydro-2-imidazolone and 2-thiazolone as building blocks for chiral polyfunctional compounds as well as chiral heterocyclic auxiliaries for asymmetric synthesis is reviewed. The stereodefined introduction of easily replaceable groups to the 4,5-olefinic moiety of the 2-oxazolone ring to give versatile chiral synthons, followed by stereospecific and stepwise substitution, provides a working and versatile strategy for achieving a chiral synthesis, which leads to the preparation of a wide variety of 2-amino alcohols of biological interest. Sterically constrained chiral 2-oxazolidinones and the derived conformationally rigid amino alcohols, which are derived from cycloaddition reactions of the 2-oxazolone to cyclic dienes such as 9,10-dimethylanthracene and hexamethylcyclopentadiene, represent excellent chiral auxiliaries and chiral ligands which are of general use in asymmetric synthesis. The strategy developed using 2-oxazolone can also be used in the cases of the structurally similar 1,3 dihydro-2-imidazolone and 2-thiazolone derivatives. PMID- 11193383 TI - [A design and development of novel polymeric prodrugs prepared by mechanochemical solid-state polymerization]. AB - The mechanochemical polymerization of solid-state monomer was first reported in 1959. Nevertheless, relatively little work has been done. We reported the first in-depth study of the mechanochemical polymerization of specially synthesized solid-state monomers, methacryloyl derivatives of bioactive compounds including detailed mechanistic implications. There are many advantages for this reaction. One of the most striking properties observed in the resulting polymers is that these polymeric prodrugs are of very low heterogeneity (narrow molecular weight distribution) which is of great value in pharmaceuticals for highly functionalized polymeric prodrugs. Thus, the present reaction provides a novel and simple methodology for the syntheses of highly functionalized polymeric prodrugs through a totally dry process. The nature of drug release from many kinds of polymeric prodrugs prepared by mechanochemical polymerization was also investigated. The rate of drug release from the polymeric prodrugs can be controlled by the property of comonomer and the structure of spacer between the main chain of polymer and drug. Several applications of polymeric prodrugs (chemoembolization and hybrid polymeric prodrugs) were also described. We have carried out the mechanochemical polymerization in the presence of pharmaceutical aids to exploit the features of this reaction. If one takes the physicochemical property of pharmaceutical aids into consideration, novel composite polymeric prodrugs possessing a variety of rates of drug release can be synthesized simultaneously with mixing. PMID- 11193384 TI - [Roles of human cytochrome P450 enzymes involved in drug metabolism and toxicological studies]. AB - Multiple forms of cytochrome P450 (P450 or CYP) enzymes play important roles in the oxidation of structurally diverse xenobiotics and endobiotics. Interindividual variations in the level and activity of P450 enzymes were investigated in the human liver microsomes. Although the total P450 content was higher in Caucasian samples than in Japanese ones, the relative levels (percentage of total P450) of individual forms of P450 determined immunochemically were not very different. CYP3A (about 30% of total P450) and CYP2C (about 20%) enzymes were major forms. Different P450 enzymes in the human liver play major roles in a variety of drug oxidations and the hepatic contents of these P450 forms could be affective to determine which P450 enzymes play major roles in drug metabolism in individual humans. Recently recombinant P450 enzymes from different sources, e.g., microsomes of human lymphoblastoid cells, of yeast, and insect cells infected with baculovirus systems, and Escherichia coli membranes containing coexpressed P450 and reductase, have been widely used for drug metabolism research. However, the marker activities or kinetic parameters of human P450 enzymes reported are not always similar. Cytochrome b5 can enhance the activities of recombinant P450 systems in some cases using different mechanisms. These differences in activities may be a critical factor for understanding the roles of human P450 enzymes involved in drug metabolism. This review provides useful information for the study of drug biotransformation in humans and for the basis of drug toxicities and carcinogenesis. PMID- 11193385 TI - [Phytochemical study of liverworts Conocephalum conicum and Chiloscyphus polyanthos]. AB - Four hundred samples of Conocephalum conicum, collected in various places have been analyzed by GC-MS. This resulted in the presence of three chemo-types of C. conicum. One of them elaborate (-)-sabinene (type-I) as a major compound. The other two types characteristically contained (+)-bornyl acetate (type-II) and methyl cinnamate (type-III) as major constituent respectively. The structures of three new monoterpenic esters, isolated from the ether extract of C. conicum (type-I and/or II) have been established by chemical and spectral means. They were shown to be monoterpenic esters of (+)-borneol and p-coumaric acid derivatives. The ether extract of the liverwort Chiloscyphus polyanthos afforded sesquiterpenoids which are enantiomeric to those found in another liverwort Lepidozia vitrea. The absolute configurations of the sesquiterpenoids found in the C. polyanthos were determined by spectroscopic evidence, chemical derivatization and/or x-ray crystallographic analysis. The ether extract of the liverwort Porella perrottetiana afforded (-)-alpha-eudesmol, which showed an opposite sign of the optical rotation to that found in higher plants. Present work on the absolute configuration and an optical purity of (-)-alpha-eudesmol strongly suggested that the positive values (e.g. +28.5 degrees) described in many previous papers should be revised. Since the absolute configuration of (-) alpha-eudesmol was identical to that (+)-beta-eudesmol found in the higher plants, it was apparent that the expression of the positive sign might be revised to (-)-alpha-eudesmol. The optical purity, reconfirmation of the absolute configuration and synthesis of (-)-alpha-eudesmol will be discussed. PMID- 11193386 TI - [Anti-carcinogenic structural modification by fluorine-substitution in aza polycyclic aromatic hydrocarbons]. AB - One of the major goals of a series of our studies is to explore the availability of a method for anti-genotoxic modification of carcinogens by fluorine substitution. Quinoline, a hepatocarcinogen, mutates bacterial tester strains in the presence of rat liver microsomal enzymes and induces GST-P (placental glutathione S-transferase)-positive foci in a medium-term bioassay system for hepatocarcinogenesis. On the other hand, 3-fluorinated quinoline (3-FQ) was neither mutagenic nor carcinogenic in the same assay system, whereas 5 fluoroquinoline (5-FQ) was mutagenic and carcinogenic. Quinoline, 3-FQ, and 5-FQ were also tested in an in vivo mutagenicity assay system using a lacZ-transgenic mouse (Muta Mouse). Mutation was induced by quinoline and 5-FQ only in the liver, the target organ of carcinogenesis by quinoline, but not in the other organs examined. 3-FQ was non-mutagenic in all of the organs. The results strongly indicate that fluorine-substitution at the position-3 of quinoline could be an anti-genotoxic structural modification of quinoline in a wide range of its genotoxic end-points. Additionally, seventeen mono- and di-fluorinated derivatives of 1,7-phenanthroline, 1,10-phenanthroline, benzo[h]quinoline, and benzo[f]quinoline were subjected to analysis of their structure-mutagenicity relationship. The results support that the enamine epoxide structure of the pyridine moiety, as well as the bay-region epoxide structure, is responsible for mutagenicity. These results suggest that the introduction of a fluorine atom to the molecule in question may be a useful tool to modify their mutagenic potency and to better understand the mechanism of mutation. PMID- 11193387 TI - [Suppressive effect of protein kinase C inhibitors on tumor cell function via phosphorylation of p53 protein in mice]. AB - We examined the role of protein kinase C (PKC) in the phosphorylation of a p53 protein. Exposure to a protein kinase inhibitor, 1-(5-isoquinolinesulfonyl)-2 methylpiperazine dihydrochloride (H7), increased the phosphorylation of the wild type p53 protein, whereas exposure to a tumor promoter phorbol ester, 12-O tetradecanoyl-phorbol-13-acetate (TPA), decreased it in vivo after incubation with mouse epidermal JB6 cells for 3 h. Exposure to a cAMP dependent protein kinase (PKA) activator, forskolin, did not decrease the phosphorylation of p53 protein. In the transient transfection/luciferase reporter transactivation assay, H7 slightly increased the mouse double minute (MDM) 2 reporter transactivation activity of the p53 protein after treatment for 24 h, whereas TPA completely blocked it. Exposure to H7 and a specific PKC inhibitor, bisindolylmaleimide (bis), dose-dependently reduced the lung-colonizing potential of highly metastatic B16-F10 mouse melanoma cells in syngeneic mice. These results suggest that the phosphorylation of the wild type p53 protein is inversely related to PKC activation, and also suggest that the phosphorylation of the p53 protein is involved in the function of its transcription factor. The PKC inhibitor may exhibit a potent anti-metastatic effect through the phosphorylation of wild type p53 protein and the activation of its function. PMID- 11193388 TI - [Control mechanisms of renal functions: effects of cardiovascular drugs on vasoconstrictive and antinatriuretic stimuli in the in vivo kidney]. AB - The kidney contributes to cardiovascular homeostasis through Na+ and water excretion and renin secretion. Changes in renal functions, therefore, have a close relationship to pathophysiology of cardiovascular diseases and to drug efficacy for them. The functions of the kidney are controlled by the sympathetic nervous system and various kinds of humoral factors and by their complicated interactions. Studies in the intact and working kidney in vivo have been providing physiologically significant information on the renal functions and drug actions. This review, by demonstrating data obtained in our laboratory with experiments in anesthetized dogs in vivo, refers mainly to the neural control of renal functions and renal actions of atrial natriuretic peptide (ANP) and an adenylate cyclase activator NKH477, either of which could be used for the treatment of congestive heart failure. Electrical stimulation of the renal nerves, which could mimic the events during elevation of renal sympathetic nerve activity, induces frequency-dependent renal norepinephrine release, renal vasoconstriction, antinatriuresis and renin secretion. ANP causes potent natriuresis and suppresses the nerve stimulation-induced renin secretion and renal vasoconstriction without affecting the norepinephrine release. Effects of ANP on other vasoconstrictive and antinatriuretic stimuli such as angiotensin II and endothelin are also demonstrated. Renal actions of NKH477 had been unknown, but we revealed that NKH477 elevates renal cAMP level and causes vasodilation and natriuresis. NKH477 also suppresses the nerve stimulation-induced renal vasoconstriction, and thereby blunts the antinatriuresis. The renal actions of these drugs clarified in our study may contribute to their curative effects on congestive heart failure. PMID- 11193389 TI - [Molecular mechanisms of DNA recognition and function by bioactive compounds]. AB - Molecular mechanisms of DNA recognition and functional expression by bioactive compounds such as bleomycin, enediyne antibiotics, and zinc finger proteins are an important research subject in the pharmaceutical scientific field. Cleavage of cellular DNA by bleomycin substantially contributes to the antitumor activity of this drug. Some physicochemical data have clearly demonstrated that the bleomycin iron (II) complex forms a dioxygen adduct species. Of special interest is the fact that the bleomycin-iron complex and cytochrome P450 have a similar dioxygen activation cycle. Probably, the site-specific iron-peroxide species of bleomycin accounts for the action mechanism of selective DNA cleavage by bleomycin. The enediyne antibiotics possess an unprecedented chemical structure, potent anticancer activity, and a fascinating mode of biological action. A new compound, C-1027, consists of a carrier apoprotein and an enediyne chromophore. The high resolution NMR experiments clarified that novel chromophore interacts with DNA through its benzoxazolinate and aminosugar moiety, and also with apoprotein through the benzoxazolinate and macrocyclic moiety. The results provide a molecular basis for the host-recognition mode, the reaction mechanism, and the drug delivery system of chromoprotein C-1027. In addition, we found unique reactivity of C-1027 chromophore toward a tRNA(Phe). RNA as well as DNA might be also a potent biological target of the enediyne antibiotics. On the basis of characteristic DNA binding mode of Cys2His2-type zinc finger motif, artificial zinc finger proteins have been created, and new functions such as DNA cleavage, long sequence binding, and DNA bending are produced. The first artificial His4 type zinc finger protein is also made from Cys-->His mutations of the Cys2His2 type transcription factor Sp1. Such novel zinc finger proteins may be useful as a gene therapeutic agent and a tool for genetic engineering. PMID- 11193390 TI - [Molecular mechanism of exocytosis in neural and immune system]. AB - Exocytosis is a common process for the secretion of physiologically active substances such as neurotransmitter, hormone, and inflammatory mediators. Exocytosis is triggered by an increase in intracellular calcium ion concentration. At the nerve terminal, voltage dependent calcium channels (VDCCs) are responsible for this calcium increase. There are several types of VDCC which are different from each other in their electro-physiological and pharmacological characteristics. In order to identify the types of VDCC at the cholinergic nerve terminal, acetylcholine (ACh) release from the electric organ synaptosomes was measured in the presence of type-specific channel blockers. At least three types of VDCC were involved in the ACh release, and N- and P/Q-type VDCC had a major contribution. Adenosine receptor A1 was coupled with N-type VDCC and had negative feedback regulation of ACh release, while A2 receptor coupled with P/Q-type VDCC enhanced the ACh release. Investigation of the inhibitory effects of antibodies from patients of autoimmune disease Lambert-Eaton syndrome on ACh release revealed that P/Q-type channel was a target for the autoantibodies. Unlike the nerve terminal, little is known about the mechanism and molecules involved in the exocytosis of immune cells. Ion channel activities of secretory granule proteins of mast cells were observed. The calcium dependency of the open probability of the channel was similar to that of histamine release from mast cells. We also showed the expression of some SNARE proteins in RBL-2H3 cells. Localization and dynamics of VAMP-7 and syntaxin-3 after antigen stimulation suggested the involvement of SNARE proteins in the exocytosis of mast cells. PMID- 11193391 TI - [Competitive binding of some alkyl p-hydroxybenzoates to human estrogen receptor alpha and beta]. AB - Alkyl p-hydroxybenzoates such as isobutyl p-hydroxybenzoate (PHBA-iBu), butyl p hydroxybenzoate (PHBA-nBu), isopropyl p-hydroxybenzoate (PHBA-iPr), propyl p hydroxybenzoate (PHBA-nPr), ethyl p-hydroxybenzoate (PHBA-Et), and methyl p hydroxybenzoate (PHBA-Me) are widely used as preservatives, stabilizers and antiseptics for medical supplies, cosmetics, foodstuffs etc. We determined the binding affinity of alkyl p-hydroxybenzoates to human estrogen receptor alpha (ER alpha) and beta (ER beta) by non-RI receptor binding assays. PHBA-iBu had a high binding affinity for ER alpha (IC50: 6.0 x 10(-6) M, the relative binding affinity (RBA): 0.267) and ER beta (IC50: 5.0 x 10(-6) M, RBA: 0.340). These IC50 values and RBA were almost the same as those of bisphenol A. The ranking of the estrogenic potency of alkyl p-hydroxybenzoates for both ERs is different; that is, PHBA-iBu > PHBA-nBu[symbol: see text]PHBA-iPr[symbol: see text]PHBA-nPr > PHBA-Et >> PHBA-Me. Alkyl p-hydroxybenzoates bound with equal relative affinity to both ER alpha and beta proteins. Alkyl p-hydroxybenzoate having a long alkyl side-chain showed a high affinity for ER alpha and beta. These findings suggest that p-hydroxybenzoates may be endocrine disruptors. PMID- 11193392 TI - [Consultation and survey for drug interaction in outpatients taking the medicines potentially interact with St. John's Wort]. AB - Ministry Health Welfare of Japan announced the caution for drug interaction of St. John's Wort (SJW), a herbal supplement occasionally used for depression, on May, 2000. Immediately after the announcement, we conducted drug consultation for outpatients prescribed the medicines potentially interacting with SJW. We provided information concerning possible drug interaction with SJW for 741 outpatients (except for pediatrics) during the period of May 22-June 16, 2000. The potential drugs prescribed frequently were warfarin (28.0%), theophylline (19.7%), digitalis (18.4%), carbamazepine (7.2%), disopyramide (6.9%) and cyclosporin (6.3%). Of the patients, 401 subjects were surveyed by collecting the questionnaires to clarify the background of SJW drug interaction. Twenty-two subjects (5.5%) have known commercially available SJW products, 5 subjects (1.2%) have ever taken SJW products before and 2 subjects (0.5%) have taken SJW products concomitant with prescribed medicines. Gender difference was observed in paying attention to SJW products; female subjects (8.6%) tended to have more interest in SJW products than male subjects (2.8%). Two subjects taking SJW have realized for the first time that the supplements they took were SJW products when their package photographs were shown at the consultation. Showing the package photographs might be helpful for making the patients easy to identify the SJW products, because most patients do not pay attention to whether the supplements contain SJW or not. It is recommended that drug consultation should be provided to avoid serious drug interaction with SJW while the outpatients are taking potential medicines prescribed. PMID- 11193393 TI - Deduced amino acid sequence and possible catalytic residues of a thermostable, alkaline cellulase from an Alkaliphilic bacillus strain. AB - Alkaliphilic Bacillus sp. strain KSM-S237 (a relative of Bacillus pseudofirmus) produces a thermostable, alkaline endo-1,4-beta-glucanase (Egl). The entire gene for the enzyme harbored a 2,472-bp open reading frame (ORF) encoding 824 amino acids, including a 30-aminoacid signal peptide. The deduced amino acid sequence of the mature enzyme (794 amino acids, 88,284 Da) showed very high similarity to those of family 5 mesophilic, alkaline Egls from some alkaliphilic bacilli. The enzyme had a region similar to a novel cellulose binding domain proposed for an Egl (EngF) from Clostridium cellulovorans. Expression of the Bacillus Egl gene in Bacillus subtilis resulted in high carboxymethy cellulase activity (2.0 g/l) in the culture broth, concomitant with the appearance of a protein band on an SDS gel at 86 kDa. Site-directed mutagenesis delineated the importance of Arg111, His151, Glu190, His262, Tyr264, and Glu305 in catalysis and/or substrate binding of the enzyme. PMID- 11193394 TI - Effect of dietary linoleate/alpha-linolenate balance on the brain lipid composition, reproductive outcome and behavior of rats during their prenatal and postnatal development. AB - The effect of the dietary linoleate (LA)/alpha-linolenate (LNA) balance during development on the brain lipid composition, reproductive outcome and behavior of rats was studied. Female rats were fed on experimental diets during pregnancy and the resulting pups for 16 weeks. The dietary LA/LNA ratios were 1.07 (LA1), 2.64 (LA2), 4.45 (LA3), 7.68 (LA4) and 10.35 (LA5). The relative content of docosahexaenoate (DHA) in the brain of pups tended to increase with decreasing LA/LNA ratio at 0 and 3 weeks, while the level of DHA was maintained constant at 16 weeks regardless of the dietary LA/LNA ratio. The learning ability was measured at 12 weeks of age, and there was no difference among the groups. In an open field test, the exploratory index was significantly lower in the LA1 group than in the LA2 group. The LA1 group had a smaller litter size and lower survival rate than the other groups. We conclude that if the diet contained appropriate amounts and balance of LA and LNA, it was possible for rats to synthesize an appropriate amount of DHA and have normal behavioral activity without DHA supplementation. PMID- 11193395 TI - Antigen binding of an ovomucoid-specific antibody is affected by a carbohydrate chain located on the light chain variable region. AB - We cloned the variable regions of heavy and light chain genes of an anti ovomucoid monoclonal antibody (MAb-OM21) produced by the mouse hybridoma cell line OM21. DNA sequence analysis showed that the light chain of the MAb-OM21 has only one potential N-glycosylation consensus sequence in the complementarity determining region 2 of the light chain. To find whether carbohydrate chains are located on the light chain, we assayed for the size of the light chain, after treatment with N-glycosidase, by western blotting, and also detection of the carbohydrate chains on the light chain was done using the lectin blot assay. A N linked carbohydrate chain has been shown to bind to the light chain. To clarify the role of this carbohydrate chain in the light chain, we produced carbohydrate variant antibodies by N-deglycosylation using glycosidase or by expressing the antibody from different host cells. The N-deglycosylated variant antibody has greater antigen binding, and the antibody produced from the different host cells showed a reduced antigen binding activity and acquired the ability to react to ovalbumin. These results suggest that antigen binding of the ovomucoid specific antibody MAb-OM21 can be affected by the carbohydrate chain on the light chain variable region. PMID- 11193396 TI - Isolation and characterization of thermotolerant Gluconobacter strains catalyzing oxidative fermentation at higher temperatures. AB - Thermotolerant acetic acid bacteria belonging to the genus Gluconobacter were isolated from various kinds of fruits and flowers from Thailand and Japan. The screening strategy was built up to exclude Acetobacter strains by adding gluconic acid to a culture medium in the presence of 1% D-sorbitol or 1% D-mannitol. Eight strains of thermotolerant Gluconobacter were isolated and screened for D-fructose and L-sorbose production. They grew at wide range of temperatures from 10 degrees C to 37 degrees C and had average optimum growth temperature between 30-33 degrees C. All strains were able to produce L-sorbose and D-fructose at higher temperatures such as 37 degrees C. The 16S rRNA sequences analysis showed that the isolated strains were almost identical to G. frateurii with scores of 99.36 99.79%. Among these eight strains, especially strains CHM16 and CHM54 had high oxidase activity for D-mannitol and D-sorbitol, converting it to D-fructose and L sorbose at 37 degrees C, respectively. Sugar alcohols oxidation proceeded without a lag time, but Gluconobacter frateurii IFO 3264T was unable to do such fermentation at 37 degrees C. Fermentation efficiency and fermentation rate of the strains CHM16 and CHM54 were quite high and they rapidly oxidized D-mannitol and D-sorbitol to D-fructose and L-sorbose at almost 100% within 24 h at 30 degrees C. Even oxidative fermentation of D-fructose done at 37 degrees C, the strain CHM16 still accumulated D-fructose at 80% within 24 h. The efficiency of L sorbose fermentation by the strain CHM54 at 37 degrees C was superior to that observed at 30 degrees C. Thus, the eight strains were finally classified as thermotolerant members of G. frateurii. PMID- 11193397 TI - High P diet induces acute secretion of parathyroidhormone without alteration of serum calcium levels in rats. AB - To find whether a high phosphorus (P) diet stimulate the secretion of PTH, a high P diet was fed to rats and an increase in serum P levels has occurred. All rats were fed a control diet (0.5% calcium (Ca), 0.5% P) for 7 days, while they were being adapted, for 1 hour at 8:00 AM and again at 8:00 PM. Four groups were switched to the high-P diet (0.5% Ca, 1.5% P) at the time of their morning meal for 1 hour. The other 4 groups continued to receive the control diet. Blood samples were collected from the rats in the remaining group, which served as a pre-feeding control. Every 30 minutes after the start of feeding (30, 60, 90, 120 min), blood samples were collected from the rats in the groups fed the control and high-P diets. Serum P concentrations increased upon intake of the high P diet, within 30 minutes after the start of feeding. Serum PTH levels also increased upon intake of the high P diet, within 30 minutes after the start of feeding, and the levels were significantly higher in the high-P group than in the control group. However, no significant difference was observed in serum Ca levels between the two groups. From these results, our findings suggest that an increase in serum P concentration might be a trigger of PTH secretion without any changes of serum calcium levels. PMID- 11193398 TI - Synthesis of optically active olivil type of lignan from L-arabinose using threo selective aldol condensation as a key reaction. AB - The threo-selective aldol condensation of (3R, 4S)-3-hydroxy-5-trityloxy-4 pentanolide, which was prepared from L-arabinose, with piperonal was applied to the stereoselective synthesis of the olivil type of lignan, (2R, 3R, 4R)-4-benzyl 4-hydroxy-3-hydroxymethyl-2-(3,4-methylenedioxyphenyl)tetrahydrofuran. PMID- 11193399 TI - Molecular cloning and sequence analysis of an endoinulinase gene from Penicillium sp. strain TN-88. AB - A genomic DNA segment and cDNAs encoding an extracellular endoinulinase of Penicillium sp. strain TN-88 were cloned and sequenced. Southern blot analysis indicated that the endoinulinase gene (inuC) was present as a single copy in the genome. An open reading frame, consisting of 1,545 bp, was not interrupted by introns, and it encoded a 25 amino acid signal peptide and a 490 amino acid mature protein. The mature protein contained three Cys residues and ten potential N-linked glycosylation sites. Three distinct transcriptional start points were observed at positions -242 (A), -215 (A), and -75 (C) from the start codon. The 5'-noncoding region had a putative TATA box at position -120 (TATATATA) and two contiguous CAAT sequences at -159 to -151. The deduced amino acid sequence showed 72 and 85% identities with those of Aspergillus niger and Penicillium purpurogenum endoinulinase genes, respectively. A neighbor-joining tree showed that fungal endoinulinases form a distinct cluster from other members of the beta fructofuranosidase superfamily and that they are more closely related to bacterial levanases than to a fungal fructosyltransferase, yeast invertases, or a yeast exoinulinase. PMID- 11193400 TI - Role of tyrosine 114 of L-methionine gamma-lyase from Pseudomonas putida. AB - L-Methionine gamma-lyase from Pseudomonas putida has a conserved tyrosine residue (Tyr114) in the active site as in all known sequences of y-family pyridoxal 5' phosphate dependent enzymes. A mutant form of L-methionine y-lyase in which Tyr114 was replaced by phenylalanine (Y114F) resulted in 910-fold decrease in kcat for alpha,gamma-elimination of L-methionine, while the Km remained the same as the wild type enzyme. The Y114F mutant had the reduced kcat by only 28- and 16 fold for substrates with an electron-withdrawing group at the gamma-position, namely O-acetyl-L-homoserine and L-methionine sulfone, respectively, and also the similar reduction of kcat for alpha,beta-elimination and deamination substrates. The hydrogen exchange reactions of substrate and the spectral changes of the substrate-enzyme complex catalyzed by the mutant enzyme suggested that gamma elimination process for L-methionine is the rate-limiting determination step in alpha,gamma-elimination overall reaction of the Y114F mutant. These results indicate that Tyr114 of L-methionine gamma-lyase is important in y-elimination of the substrate. PMID- 11193401 TI - Purification and characterization of novel transglutaminase from Bacillus subtilis spores. AB - Transglutaminase activity was detected in suspensions of purified spores prepared from lysozyme-treated sporulating cells of Bacillus subtilis AJ 1307. The enzyme was easily solubilized from the spores upon incubation at pH 10.5 at 37 degrees C. The transglutaminase activity was separated into two fractions upon purification by hydrophobic interaction chromatography (TG1 and TG2). Each enzyme was purified to electrophoretic homogeneity (about 1,000-fold). Both enzymes had the same molecular weight of 29,000 as estimated by SDS-PAGE, had the same N terminal 30 amino acid sequence, and also showed the same optimal temperature (60 degrees C) and pH (8.2). The purified enzyme catalyzed formation of cross-linked epsilon-(gamma-glutamyl)lysine isopeptides, resulting in the gel-formation of protein solutions such as alphas-casein and BSA. PMID- 11193402 TI - Characterization of O-acetyl-L-serine sulfhydrylase purified from an alkaliphilic bacterium. AB - O-Acetyl-L-serine sulfhydrylase (EC 4.2.99.8) activity was shown to be very high compared with O-acetyl-L-homoserine sulfhydrylase (EC 4.2.99.10) activity and L cystathionine cleaving activities, in an extract of cells of an alkaliphilic bacterium grown in a synthetic medium. The synthesis of the first enzyme was repressed by approximately 55% by both L-cystine and L-djenkolic acid added to the medium at a concentration of 0.5 mM, but L-methionine (1 mM) and S-adenosyl-L methionine (0.5 mM) affected it to lesser extents. Its enzyme activity was inhibited by 25% and 12% by methionine (10 mM) and S-adenosylmethionine (5 mM), respectively. The enzyme was purified from the extract through ammonium sulfate fractionation, heat treatment, and chromatography on columns of DEAE-cellulose, Sephacryl S-300, and Octyl Sepharose CL-4B with a recovery of 21%. Polyacrylamide gel electrophoresis with sodium dodecylsulfate of the preparation obtained finally showed its homogeneity and the molecular mass of 37,000 Da for dissociated subunits. Gel filtration of the enzyme on a Sephacryl S-300 column showed an approximate molecular mass of 72,000 Da, suggesting that the enzyme was comprised of two identical subunits. The enzyme catalyzed the beta-replacement reaction with O-acetylserine as a substrate, and showed no reactivity to other O substituted amino acids tested. The reaction proceeded best at 40 degrees C (when tested at pH 7.5), and at pH 6.5 (at 40 degrees C). The enzyme kept 90% its activity after incubation at 65 degrees C (at pH 7.5) for 30 min, and more than 90% after 30 min incubation at pHs 7-12 at 30 degrees C. The enzyme had a Km of 4 mM for O-acetyl-L-serine and a Vmax of 37.0 micromol/min/mg of protein, a very low value compared with those of other organisms. However, the content of the enzyme in the extract was calculated to be approximately 3.5% total protein. Sensitivity of the enzyme to carbonyl reagents was very low, although it was shown to have pyridoxal 5'-phosphate as a cofactor by examination of its absorption spectrum. Sulfhydryl reagents tested showed no inhibition. The novelty of this enzyme among analogous sulfhydrylases purified from other organisms was discussed. PMID- 11193403 TI - Purification and characterization of thermostable pectate lyase with protopectinase activity from thermophilic Bacillus sp. TS 47. AB - A strain of thermophilic bacterium, Bacillus sp., with pectolytic activity has been isolated. It produced an extracellular endo-polygalacturonate trans eliminase (PL, EC 4.2.2.1) when grown at 60 degrees C on a medium containing polygalacturonate (PGA). The PL was purified by hydrophobic, cation exchange, and size exclusion column chromatographies. The molecular mass of the enzyme was 50 kDa by SDS-PAGE. The isoelectric point of the enzyme was pH 5.3. The enzyme had a half-life of 13 and 1 h at 65 and 70 degrees C, respectively, and showed optimal activity around at 70 degrees C and pH 8.0. It had protopectinase activity, besides PL activity, on lemon protopectin and cotton fibers. The first 20 amino acids sequence of the enzyme had significant similarity with that of PL from methophilic Bacillus subtilis, with 50% identity. PMID- 11193404 TI - Potent inhibition of macrophomate synthase by reaction intermediate analogs. AB - Potent inhibitors for macrophomate synthase, which has recently been found to catalyze a highly unusual five-step chemical transformation, were explored. Among 11 oxalacetate analogs tested, only three analogs had moderate to relatively strong inhibitory activities (I50 1.3-8.1 mM). On the other hand, among 35 bicyclic intermediate analogs synthesized, two diacids were found to be the most potent inhibitors (I50 0.80, 0.84 mM) which had a much higher affinity than that of the natural substrate 2-pyrone. (-)-Enantiomers of the diacids showed 30 times stronger activity (I50 0.34, 0.41 mM) than (+)-ones. The I50/Km values (0.20, 0.24) showed their potent inhibitions. Competitive inhibitions were observed in two representative inhibitors. PMID- 11193405 TI - Qualitative and quantitative analysis of endogenous jasmonoids in potato plant (Solanum tuberosum L.). AB - Qualitative and quantitative analyses of endogenous jasmonoids were done by liquid chromatography/ selected ion monitoring (LC-SIM) using deuterium-labeled compounds as internal standards. To prove the practicality of this way of analyzing the contents of endogenous jasmonoids in plants, the method was used for estimating jasmonoids in potato plants. PMID- 11193406 TI - Gordonan, an acidic polysaccharide with cell aggregation-inducing activity in insect BM-N4 cells, produced by Gordonia sp. AB - An acidic polysaccharide, termed gordonan, was isolated from the culture medium of Gordonia sp. as an inducer of cell aggregation in an insect cell line, BM-N4. Gordonan had an average molecular weight of 5 x 10(6) and its structure was identified as -->3)-4-O-(1-carboxyethyl)-beta-D-Manp-(1-->4)-beta-D-GlcAp-(1-->4) beta-D-Glcp-(1--> mainly by acid hydrolysis experiments and NMR analysis. It induces cell aggregation at the concentration of 4 microg/ml. A partially hydrolyzed polysaccharide derived from gordonan with a molecular weight of 5 x 10(5) showed weak activity, while any fragment molecules with lower molecular weights prepared from gordonan showed no activity. PMID- 11193407 TI - Dietary antioxidants fail in protection against oxidative genetic damage in in vitro evaluation. AB - Carcinogenesis is believed to be induced through the oxidative damage of DNA, and antioxidants are expected to suppress it. So, the polyphenolic antioxidants in daily foods were investigated to see whether they protect against genetic damage by active oxygen. In the evaluation, we used a bioassay and a chemical determination, a Salmonella mutagenicity test for mutation by a N-hydroxyl radical from one of the dietary carcinogens 3-amino-1-methyl-5H-pyrido[4,3 b]indole and the formation of 8-hydroxyl (8-OHdG) from 2'-deoxyguanosine (2'-dG) in a Fenton OH-radical generating system. Thirty-one antioxidants including flavonoids were compared in terms of radical-trapping activity with bacterial DNA and 2'-dG. Antioxidants inhibited the mutation but the IC50 values were in the mM order. Against 8-OHdG formation, only alpha-tocopherol had a suppressive effect with an IC50 of 1.5 microM. Thus, except alpha-tocopherol, the dietary antioxidants did not scavenge the biological radicals faster than bacterial DNA and intact 2'-dG, indicating that they failed to prevent oxidative gene damage and probably carcinogenesis. PMID- 11193408 TI - Two novel diterpenoids, erinacines H and I from the mycelia of Hericium erinaceum. AB - Novel diterpenoids, erinacines H (1) and I (3), were isolated from the cultured mycelia of Hericium erinaceum. The structures of the compounds were determined by interpretation of the spectral data. Erinacine H showed stimulating activity of nerve growth factor (NGF)-synthesis. PMID- 11193409 TI - Synthesis of novel heterobranched beta-cyclodextrins from alpha-D mannosylmaltotriose and beta-cyclodextrin by the reverse action of pullulanase, and isolation and characterization of the products. AB - Alpha-D-mannosyl-maltotriose (Man-G3) were synthesized from methyl alpha mannoside and maltotriose by the transfer action of alpha-mannosidase. (Man-G3) betaCD and (Man-G3)2-betaCD were produced in about 20% and 4% yield, respectively when Aerobacter aerogenes pullulanase (160 units per 1 g of Man-G3) was incubated with the mixture of 1.6 M Man-G3 and 0.16 M betaCD at 50 degrees C for 4 days. The reaction products, (Man-G3)-betaCD were separated to three peaks by HPLC analysis on a YMC-PACK A-323-3 column and (Man-G3)2-betaCD were separated to several peaks by HPLC analysis on a Daisopak ODS column. The major product of (Man-G3)-betaCDs was identified as 6-O-alpha-(6(3)-O-alpha-D mannosylmaltotriosyl)-betaCD by FAB-MS and NMR spectroscopies. The structures of (Man-G3)2-betaCDs were analyzed by TOF-MS and NMR spectroscopies, and confirmed by comparison of elution profiles of their hydrolyzates by alpha-mannosidase and glucoamylase on a graphitized carbon column with those of the authentic di glucosyl-betaCDs. The structures of three main components of (Man-G3)2-betaCDs were identified as 6(1),6(2)-, 6(1),6(3)- and 6(1),64-di-O-(63-O-alpha-D-mannosyl maltotriosyl)-betaCD. PMID- 11193410 TI - Gene cloning, purification, and characterization of two cyanobacterial NifS homologs driving iron-sulfur cluster formation. AB - Iron-sulfur proteins are essential in the photosynthetic system and many other biological processes. We have isolated and characterized enzymes driving the formation of iron-sulfur clusters from Synechocystis sp. PCC6803. Two genes (slr0387 and sll0704), showing similarity to nifS of Azotobacter vinelandii, were cloned, and their gene products (SsCsdl and SsCsd2) were purified. They catalyzed the desulfuration of L-cysteine. Reconstitution of a [2Fe-2S] cluster of cyanobacterial ferredoxin proceeded much faster in the presence of L-cysteine and either of these enzymes than when using sodium sulfide. These results suggest that SsCsdl and SsCsd2 facilitate the iron-sulfur cluster assembly by producing inorganic sulfur from L-cysteine. Synechocystis sp. PCC6803 has no gene coding for a protein with similarity to the N-terminal domain of NifU of A. vinelandii, which is believed to cooperate with NifS to assemble iron-sulfur clusters. Thus, the cluster formation in the cyanobacterium probably proceeds through a mechanism that is different from that in A. vinelandii. PMID- 11193411 TI - A novel lantibiotic, nukacin ISK-1, of Staphylococcus warneri ISK-1: cloning of the structural gene and identification of the structure. AB - Staphylococcus warneri ISK-1, which we had previously reported as Pediococcus sp. ISK-1, produces a novel bacteriocin, nukacin ISK-1. Edman degradation of the chemically reduced nukacin ISK-1 produced a sequence of 27 amino acids, 7 of which were unidentified. Using single-specific-primer-PCR product as a probe, a 3.6-kb HindIII fragment containing the nukacin ISK-1 structural gene (nukA) was cloned and sequenced. The deduced amino acid sequence of nukacin ISK-1 had 57 amino acids, including a 30-amino acid leader region. The propeptide sequence showed significant similarity to those of lacticin-481 type lantibiotics. In the region upstream of nukA, a part of a long open reading frame (ORF), designated as nukM, encoding a putative modification enzyme was oriented in the opposite direction. In the region downstream of nukA, ORF1 was found in which the sequence of the putative translational product was similar to various response regulatory proteins. PMID- 11193412 TI - Synthesis and tumor-promoting activities of 12-Epi-phorbol-12,13-dibutyrate. AB - 12-Epi-phorbol-12,13-dibutyrate (1), the C12-epimer of the most frequently used phorbol ester probe, phorbol-12,13-dibutyrate (PDBu), has been synthesized from phorbol in 9 steps in order to investigate the structural requirements for tumor promoting activity. Compound 1 showed about 100-fold weaker in vitro biological activities related to in vivo tumor promotion, Epstein-Barr virus early antigen (EBV-EA)-inducing ability, superoxide (O2-) generation-inducing ability, and binding to the protein kinase C (PKC) regulatory domain surrogate peptides. The results indicated that the beta-stereochemistry at position 12 of the phorbol skeleton is important for optimal activity. Binding selectivity to each PKC C1 domain of 1 was almost equal to that of PDBu. PMID- 11193413 TI - Expression of soluble bovine pancreatic ribonuclease A in Pichia pastoris and its purification and characterization. AB - A Pichia pastoris expression system for bovine pancreatic RNase A was constructed: the RNase A sequence was fused to the PHO1 signal and the AOX1 promoter was used for efficient secretion. Approximately 5 mg of soluble enzymes were secreted per liter of the culture, but one half of them were glycosylated. After a series of purifications by cation-exchange chromatography, the glycosylated enzyme was removed and the pure recombinant soluble unglycosylated RNase A was obtained in the final yield of 1 mg per liter of the culture. N Terminal sequence, molecular weight, secondary structure, thermal stability, and activity were completely identical with those of commercial RNase A. Glycosylated RNase A had a decreased kcat, 60-70% of the activity of wildtype RNase A, as in the case of RNase B. Its carbohydrate moiety seemed to destabilize the enzyme differently from RNase B since Tm of the glycosylated RNase A was decreased by 6 degrees C. The carbohydrate moiety of the glycosylated enzyme contained no GlcNAc. The N34A mutant RNase A, in which the only potential N-glycosylation site, Asn34, is mutated to alanine, was also glycosylated, implying that glycosylation is not N-linked but O-linked. PMID- 11193414 TI - Family 19 chitinases from Streptomyces thermoviolaceus OPC-520: molecular cloning and characterization. AB - Family 19 chitinase genes, chi35 and chi25 of Streptomyces thermoviolaceus OPC 520, were cloned and sequenced. The chi35 and chi25 genes were arranged in tandem and encoded deduced proteins of 39,762 and 28,734 Da, respectively. Alignment of the deduced amino acid sequences demonstrated that Chi35 has an N-terminal domain and a catalytic domain and that Chi25 is an enzyme consisting of only a catalytic domain. Amino acid sequences of the catalytic domains of both enzymes, which are highly similar to each other, suggested that these enzymes belong to the family 19 chitinases. The cloned Chi35 and Chi25 were purified from E. coli and S. lividans as a host, respectively. The optimum pH of Chi35 and Chi25 were 5-6, and the optimum temperature of Chi35 and Chi25 were 60 and 70 degrees C, respectively. Chi35 bound to chitin, Avicel, and xylan. On the other hand, Chi25 bound to these polysaccharides more weakly than did Chi35. These results indicate that the N-terminal domain of Chi35 functions as a polysaccharide-binding domain. Furthermore, Chi35 showed more efficient hydrolysis of insoluble chitin and stronger antifungal activity than Chi25. In the polysaccharide-binding domain of Chi35, there are three reiterated amino acid sequences starting from C-L-D and ending with W, and the repeats were similar to xylanase (STX-I) from the same strain. However, the repeats did not show sequence similarity to any of the known chitin-binding domains and cellulose-binding domains. PMID- 11193415 TI - Purification of stearidonic acid (18:4(n-3)) and hexadecatetraenoic acid (16:4(n 3)) from algal fatty acid with lipase and medium pressure liquid chromatography. AB - Stearidonic acid (18:4(n-3)) and hexadecatetraenoic acid (16:4(n-3)) are included in some edible marine algae such as Undaria pinnatifida and Ulva pertusa with relatively high compositions (up to 40%) of total fatty acids. In order to prepare 16:4(n-3) and 18:4(n-3) enriched fatty acid concentrates, we screened for a suitable lipase which concentrates these acids by the removal of other fatty acids in the selective esterification reaction reported by Shimada et al. (Shimada et al. (1997), J. Am. Oil Chem. Soc., 74, 1465-1470). In combination with the lipase reaction and reversed-phase medium pressure liquid chromatography, we purified 18:4(n-3) and 16:4(n-3) to more than 95% purity. PMID- 11193416 TI - Inhibition of alpha-glucosidase and amylase by luteolin, a flavonoid. AB - Twenty-one naturally occurring flavonoids were tested for inhibitory activities against alpha-glucosidase (EC 3.2.1.20) and alpha-amylase (EC 3.2.1.1). Luteolin, amentoflavone, luteolin 7-O-glucoside, and daidzein were the strongest inhibitors among the compounds tested. Luteolin inhibited alpha-glucosidase by 36% at the concentration of 0.5 mg/ml and was stronger than acarbose, the most widely prescribed drug, in inhibitory potency, suggesting that it has the possibility to effectively suppress postprandial hyperglycemia in patients with non-insulin dependent diabetes mellitus. Luteolin also inhibited alpha-amylase effectively although it was less potent than acarbose. The clinical value of luteolin needs to be further evaluated. PMID- 11193417 TI - Increases in 1,5-anhydroglucitol levels in germinating amaranth seeds and in ripening banana. AB - To examine whether 1,5-anhydroglucitol (AG) is derived from starch degradation in plant tissues, we colorimetrically measured AG contents of germinating amaranth seeds and ripening banana pulp. In both cases, as starch degradation proceeded, AG levels were significantly increased, but were 1,700-5,000 times lower than those of total soluble carbohydrates. alpha-1,4-Glucan lyase activity, which is measured by the 1,5-anhydrofructose (AF) liberated from non-reducing glucose residues of starch or glycogen, was too low to be detected in amaranth or banana by the 3,5-dinitrosalicylic acid method. On the other hand, AF reductase, which reduces AF to AG, was detected in germinating amaranth seeds and banana pulp. Thus, the increases in AG levels are conceived to be derived from starch breakdown, although further investigation is needed to answer whether the starch degradation pathway via alpha-1,4-glucan lyase/AF reductase exists in plant tissues. PMID- 11193418 TI - Influence of exogenous natural oils on the omega-1 and omega-2 hydroxy fatty acid moiety of sophorose lipid produced by Candida bombicola. AB - Candida bombicola can synthesize monohydroxy fatty acid as a moiety of sophorose lipids. The hydroxy fatty acids contained in a major lactone were identified by GC-MS, after culturing with natural oils such as coconut, rapeseed, olive, and soybean oils. Hydroxy fatty acids of C18 and C16 were always synthesized, but differences were observed among the oils regarding the positions of hydroxyl groups, unsaturation, and composition of the fatty acids. A new C17 hydroxy acid was found without addition of oil. PMID- 11193419 TI - Dietary beta- and gamma-cyclodextrins stimulation of hepatic metallothionein gene expression in rats. AB - This study investigated whether hepatic metallothionein gene expression is affected by dietary cyclodextrins. Young male Wistar rats were fed a basal diet or cyclodextrin-supplemented (50 g of cyclodextrin per kg diet) diets for 7 d. Copper content in the liver did not show any significant changes among rats fed the basal, beta- and gamma-cyclodextrin diets. There were no differences in liver or serum zinc among groups. Copper content in serum was markedly decreased in rats fed the gamma-cyclodextrin-supplemented diet. Liver metallothionein mRNA levels were significantly elevated in both beta- and gamma-cyclodextrins-fed rats, but not in alpha-cyclodextrin-fed rats. Thus, the increase in hepatic metallothionein mRNA levels might be due to this mechanism except for the contents of copper and zinc in the liver. PMID- 11193420 TI - Simple synthesis of 5,9-dimethylated long-chain alkanes, the sex pheromones of leaf miner moths. AB - Each stereoisomeric mixture of 5,9-dimethylpentadecane and 5,9 dimethylhexadecane, the major and the minor sex pheromone components of Perileucoptera coffeella, respectively, was synthesized in about 25% overall yield through 6 steps from beta-citronellol. 5,9-Dimethylheptadecane, the major sex pheromone component of Leucoptera malifoliella, was also synthesized analogously as a stereoisomeric mixture in a 22% overall yield. PMID- 11193421 TI - Affinity of placental decorin for collagen. AB - Decorin was isolated from 7 M urea extract of bovine placental cotyledons by ion exchange and hydrophobic chromatography. Decorin and its core protein showed a broad band at about 115 kDa and a single band at 47 kDa, respectively by SDS PAGE. Anti-decorin core protein antiserum from pig skin was reacted with placental decorin and its core protein in western blotting. The NH2-terminal amino acid sequence of core protein from placental cotyledons was not different from that of core protein from skin and bone. Glycosaminoglycan of decorin was identified as dermatan sulfate by electrophoresis on a cellulose-acetate membrane and chondroitinase digestivity. Decorin bound to collagen in the order for type III, I, and V. PMID- 11193422 TI - Elongation factor 2 in the liver and skeletal muscle of mice is decreased by starvation. AB - We examined whether starvation affected the amount of EF-2 protein as well as the level of its mRNA in the liver and skeletal muscle of mice, to understand the molecular mechanism for nutritional adaptation of protein-turnover. Although the amount of EF-2 was diminished by starvation in each of the tissues examined, the amount of EF-2 mRNA did not decrease in parallel with the protein. PMID- 11193423 TI - Compilation and characterization of histidine-containing phosphotransmitters implicated in His-to-Asp phosphorelay in plants: AHP signal transducers of Arabidopsis thaliana. AB - Histidine (His)-to-Aspartate (Asp) phosphorelay signal transduction systems are generally made up of a "sensor histidine (His)-kinase", a "response regulator", and a "histidine-containing phosphotransmitter (HPt)". In the higher plant, Arabidopsis thaliana, results from recent intensive studies suggested that the His-to-Asp phosphorelay mechanism is at least partly responsible for propagation of environmental stimuli, such as phytohormones (e.g. ethylene and cytokinin). Here we compiled the members of the HPt family of phosphotransmitters in Arabidopsis thaliana (AHP-series, Arabidopsis HPt phosphotransmitters), based on both database and experimental analyses, in order to provide a comprehensive basis at the molecular level for understanding the function of the AHP phosphotransmitters that are implicated in the His-to-Asp phosphorelay of higher plants. PMID- 11193424 TI - Molecular cloning and characterization of a cDNA for a rice Sec31p homolog. AB - A cDNA for a putative Sec31p in rice has been cloned and sequenced. In yeast, Sec31p is a component of a protein-coated vesicle, COPII, which functions in the transport of cargo proteins from the endoplasmic reticulum to the cis-Golgi network. Structural similarities between yeast Sec31p and the rice putative homolog are discussed. PMID- 11193425 TI - Identification and characterization of a novel gene, hos2+, the function of which is necessary for growth under high osmotic stress in fission yeast. AB - hos2 mutants of the fission yeast Schizosaccharomyces pombe showed the phenotype of high osmolarity sensitivity for growth. An S. pombe strain carrying the hos2 M10 allele cannot form colonies on agar plates containing 2 M glucose, but the parental strain can do so very well, as demonstrated previously. In this study, the hos2+ gene was identified as one that encodes a small protein of 94 amino acids, which shows no sequence similarity to any other proteins in the current databases. The hos2-M10 mutation resulted in Gln-62 to TAG-termination codon. A Hos2-defective (hos2delta) strain, which we then constructed, showed the phenotype of high osmolarity sensitivity, as in the case of the original hos2-M10 mutant. For this hos2delta mutant, three multicopy suppressor genes were isolated and one of which was identified as the pgk1+ gene, encoding a phosphoglycerate kinase. PMID- 11193426 TI - Tributyrin specifically induces a lipase with a preference for the sn-2 position of triglyceride in Geotrichum sp. FO401B. AB - The extracellular Lipases A and C produced by Geotrichum sp. FO401B have a preference for the sn-1,3 and sn-2 positions of triglyceride, respectively. Total production of these lipases was increased by plant oils and tributyrin. Butyl Toyopearl column chromatography demonstrated that only Lipase C was produced in the presence of tributyrin. Lipase C hydrolysed natural fats except sardine oil preferentially at the sn-2 position, but it showed little stereoselectivity for triolein. PMID- 11193427 TI - Inhibition by (+)-persenone [corrected] A-related compounds of nitric oxide and superoxide generation from inflammatory leukocytes. AB - We have previously reported that persenone A, isolated from avocado fruit, is an effective inhibitor of both nitric oxide (NO) and superoxide (O2-) generation in cell culture systems. In this study, we have prepared four persenone A-related compounds and examined their inhibition of NO and O2- generation from inflammatory leukocytes. Some structural importance in persenone A to attenuate free radical generation is discussed. PMID- 11193428 TI - An avocado constituent, persenone A, suppresses expression of inducible forms of nitric oxide synthase and cyclooxygenase in macrophages, and hydrogen peroxide generation in mouse skin. AB - We investigated the suppressive effects of an avocado constituent, persenone A, on lipopolysaccharide- and interferon-y-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) in a mouse macrophage cell line RAW 264.7. Persenone A at concentration of 20 microM almost completely suppressed both iNOS and COX-2 protein expression. In mouse skin, double treatments with persenone A (810 nmol) significantly suppressed double 12-O-tetradecanoylphorbol-13-acetate (TPA, 8.1 nmol) application-induced hydrogen peroxide (H2O2) generation. Treatment with persenone A before the second TPA treatment was sufficient to inhibit H2O2 generation, while the first treatment was not. This study thus suggests that persenone A is a possible agent to prevent inflammation-associated diseases including cancer. PMID- 11193429 TI - Regulation of virulence factors of enterohemorrhagic Escherichia coli O157:H7 by self-produced extracellular factors. AB - Enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes serious diarrhea and hemolytic uremic syndrome in humans. The expressions of EspD and intimin by O157:H7 have now been shown to be down-regulated by medium conditioned by O157:H7 grown at stationary phase. Preparation of conditioned medium showing the effect on the amount of EspD was not dependent on temperature or growth medium, but was dependent on growth phase. Inhibition of EspD and intimin expression was also induced by medium conditioned by E. coli K-12 strains and homoserine lactone, a signal molecule of the quorum-sensing system in gram-negative bacteria. These results suggest the possibility that the quorum-sensing system mediated by self produced extracellular factors plays an important role in control of colonization of EHEC O157:H7. PMID- 11193430 TI - Molecular cloning of the gene encoding an outer-membrane-associated beta-N acetylglucosaminidase involved in chitin degradation system of Alteromonas sp. strain O-7. AB - The gene encoding beta-N-acetylglucosaminidase (GlcNAcaseA) was cloned using PCR with degenerate oligonucleotide primers from the partial amino acid sequence of the enzyme. The gene encoded a polypeptide of 863 amino acids with a predicted molecular mass of 97kDa. A characteristic signal peptide, which was present at the amino-terminus of the precursor protein, contained four amino acids (Ala-Gly Cys-Ser) identical in sequence and location to the processing and modification sites of the outer membrane lipoprotein of Escherichia coli, indicating that the mature GlcNAcaseA is a lipoprotein the N-terminal cysteine residue of which would be modified by the fatty acid that anchors the protein in the membrane. The predicted amino acid sequence of GlcNAcaseA showed similarity to bacterial beta-N acetylglucosaminidases belonging to the family 20 glycosyl hydrolases. PMID- 11193431 TI - Binding affinity of the methyl ester of AK-toxin I to membrane fractions from Japanese pear leaves. AB - The binding site of AK-toxin, a host-specific toxin against Japanese pear, was searched for in the membrane fractions of the pear leaves, using 3H-labeled AK toxin I methyl ester. Binding activity, which was displaceable by the unlabeled ligand, was observed for microsomal fraction from a toxin-susceptible cultivar, Nijisseiki. However, the binding was also observed for those from toxin-resistant cultivars, Kosui and Hosui. Detection of the specific binding failed for the plasma membrane fraction which was prepared from microsomal fraction of the toxin susceptible cultivar by aqueous two-phase separation, and the hitherto presumed model of the AK-toxin receptor in the plasma membrane could not be verified. PMID- 11193432 TI - [Clinical application of reticulated platelet analysis using the matic-modified thiazole orange method and flow cytometry]. AB - Reticulated platelet (RP) analysis using thiazole orange (TO) and a flow cytometer is a convenient and promising method for estimating platelet kinetics in patients with thrombocytopenia. Among many different modifications of the TO method, a novel protocol reported by Matic in 1998 seems to be superior because it allows RP analysis using a sample of whole blood very quickly and accurately. Therefore, we used this method to analyze platelet kinetics in patients with idiopathic thrombocytopenic purpura (ITP) and hemophagocytic syndrome (HPS), as well as patients with hematopoietic malignancies (HM) after intensive chemotherapy. The proportion of RP was increased in the patients with ITP and HPS, and furthermore showed a negative linear correlation with the platelet count. The change in the proportion of RP occurred about one week before the change in the circulating platelet count in the patients with HM after chemotherapy. This modification of the TO method by Matic is expected to become a standard protocol for RP analysis. PMID- 11193433 TI - [Idiopathic mediastinal and subcutaneous emphysema in a patient with acute lymphocytic leukemia after allogeneic bone marrow transplantation]. AB - A 45-year-old man was diagnosed as having Ph1+ acute lymphocytic leukemia (ALL) in February 1997. Complete remission was achieved by chemotherapy. Allogeneic BMT from his HLA-identical sister was performed on June 11, 1997. Engraftment was relatively quick, but acute GVHD (grade I) developed. The patient was discharged on day 113. Seven months after BMT, in January 1998, exertional dyspnea developed gradually. Chest X-ray examination showed diffuse interstitial pneumonia, for which corticosteroid was started immediately. The symptoms and signs gradually improved. However, on the 20th hospital day (February 23), bilateral subcutaneous emphysema developed in the neck and supraclavicular region. Chest X-ray and CT examinations showed pneumomediastinum without pneumothorax. The pneumomediastinum and subcutaneous emphysema gradually subsided after 3 weeks of bed rest. Subcutaneous emphysema and pneumomediastinum are relatively rare complications of allogeneic BMT. PMID- 11193434 TI - [Clinical features of essential thrombocythemia in three children]. AB - Essential thrombocythemia (ET) is one of the quite rare myeloproliferative disorders in children. The natural course and outcome of this disease have been reported to vary. We report three children (two boys and one girl, mean age at diagnosis 12 yr) with ET who showed different clinical courses. The girl was asymptomatic, but the boys had ankle pain and priapism, respectively. The platelet count ranged between 2300 and 2900 x 10(9)/L, and the diagnoses were made according to the criteria of the Polycythemia Vera Study Group. The serum thrombopoietin level reached 0.33 and 0.47 fmol/ml in two patients. All three children were administered aspirin or dipyridamole orally. Normalization of the platelet count was observed in two patients, and stable disease persisted in one. The 12 pediatric patients with ET reported previously in Japan demonstrated a low incidence of serious thrombohemorrhagic complications and a favorable outcome, none developing acute leukemia. Careful continuous observation and conservative treatment may be preferable in pediatric patients who do not have cardiovascular symptoms, avoiding the use of potential leukemogens such as alkylating agents and hydroxyurea. PMID- 11193435 TI - [Cytomegalovirus mononucleosis with severe thrombocytopenia]. AB - In October 1998, a 37-year-old man was admitted because of petechiae and thrombocytopenia following flu-like symptoms. On admission, there were numerous petechiae on the back and extremities. The WBC count was 3,700/microliter with 3% atypical lymphocytes, the lymphocyte CD4/CD8 ratio 0.37, and the platelet count 1,000/microliter. Mild splenomegaly was detected by CT. Results of blood chemistry and coagulation tests were normal. A bone marrow aspirate was normocellular with no signs of dysplasia, and the megakaryocyte count was normal. The patient was initially diagnosed as having virus infection-associated thrombocytopenia. Steroid therapy was started immediately, and the platelet count rose to 15 x 10(4)/microliter on day 21. The PA-IgG level was 652 ng/10(7) platelets. Mild liver dysfunction developed, and atypical lymphocytes increased in number thereafter. Because IgM anti-cytomegalovirus (CMV) antibody (Ab) was positive and IgG CMV Ab was negative, a diagnosis of CMV mononucleosis was made. Gancyclovir was therefore started. Four months later, steroid therapy was discontinued, and partial remission has since been maintained. In healthy individuals, CMV infection is usually latent, and the development of mononucleosis is rare. So far, 11 cases of CMV-induced mononucleosis associated with severe thrombocytopenia have been reported in immunocompetent adults. PMID- 11193436 TI - [Retardation of platelet recovery after autologous stem cell transplantation in a patient with acute lymphoblastic leukemia: possible role of decreased thrombopoietin production by bone marrow stromal cells]. AB - A 16-year-old boy was diagnosed as having acute lymphoblastic leukemia and underwent autologous stem cell transplantation at the time of his second complete remission. Retardation of platelet recovery was evident at day 90 (< 5 x 10(4)/microliter), and at day 660 after transplantation the platelet count was 8.5 x 10(4)/microliter. Neutrophils and RBCs showed only slightly retarded recovery. Bone marrow stromal cells, which are thought to play an integral role in megakaryopoiesis, were examined. Although TPO mRNA expression per cell was normal, CFU-F was significantly decreased, resulting in a decrease of total TPO mRNA expression. In contrast, expression of G-CSF mRNA per cell was increased. It was thought that chemotherapy before bone marrow transplantation may have reduced the number of stromal cells, leading to retardation of platelet recovery because of low TPO expression. PMID- 11193437 TI - [Disseminated MALT lymphoma associated with macroglobulinemia]. AB - We report a case of disseminated MALT lymphoma with macroglobulinemia in an 80 year-old man who presented with a persistent fever. A radiograph of the chest showed infiltration of the left lung and pleural effusion of the right lung. The fluid contained numerous atypical lymphoid cells, which were positive for CD19, CD20, and HLA-DR, and negative for CD5 and CD10. Analysis of a pleural biopsy sample demonstrated no abnormality. A CT scan of the abdomen showed extensive thickening of the wall of the stomach adjacent to a peritoneal mass. Endoscopic examination disclosed antral ulceration. Histopathological examination of gastric samples revealed infiltration by centrocyte-like cells and lymphoepithelial lesions. Serum electrophoresis detected a macroglobulin peak at 34.5 g/l, and immunoelectrophoresis revealed an IgM kappa component. A bone marrow aspirate showed infiltration by the same lymphoid cells as those in the pleural fluid. A chromosome study of the lymphoid cells from both the bone marrow and pleural fluid showed a normal karyotype. The final diagnosis was MALT lymphoma involving the stomach, lungs and bone marrow. The patient did not consent to chemotherapy, and instead was given oral prednisolone. He died of respiratory distress one year and four months after diagnosis. Autopsy revealed wide dissemination of the tumor cells. PMID- 11193438 TI - [Intravascular large B-cell lymphoma associated with hypoalbuminemia and hypoxemia]. AB - A 67-year-old man was referred to our hospital for treatment of hemophagocytic syndrome. Hypotension, hypoxemia, pleural effusion, severe anasarca, and splenomegaly were noticed at the time of admission. Laboratory findings showed anemia (7.7 g/dl), thrombocytopenia (4.5 x 10(4)/microliter), an increase of serum LDH (1,466 IU/L) and severe hypoalbuminemia (1.9 g/dl). Bone marrow aspiration revealed an increase of reticulum cells with active hemophagocytosis and the presence of immature lymphocytes (6.0%). Lymphoma was suspected, but effective chemotherapy could not be performed because of progressive hypoxemia and severe hypoalbuminemia, and the patient died of the disease 2 weeks after admission. Autopsy revealed large lymphoid cells packed within systemic vessels as well as invasion into organs such as the liver, lungs, and spleen. The postmortem diagnosis was intravascular large B-cell lymphoma. Hypoalbuminemia and hypoxemia appear to be important clinical features of intravascular large B-cell lymphoma. PMID- 11193439 TI - [Development of factor VIII inhibitor in three non-hemophiliac patients]. AB - Infrequently, inhibitors against factor VIII can develop in non-hemophiliac patients and cause serious bleeding. In the last year, we have experienced 3 non hemophiliac patients who developed factor VIII inhibitors. Here, we describe the clinical courses of the three patients and the characteristics of the inhibitors. Case 1: A 69-year-old man underwent a partial gastrectomy because of early gastric cancer, and one month later developed signs of a bleeding tendency such as hematemesis, tarry stools and intramuscular hemorrhage. Blood coagulation tests revealed prolongation of the activated partial thromboplastin time (aPTT), which had been normal on admission. Case 2: A 78-year-old woman with no previous disease history developed generalized subcutaneous purpura. Blood coagulation tests performed on admission revealed a prolonged aPTT. Case 3: A 30-year-old man was admitted to an emergency hospital because of left intrapleural hemorrhage and liver injury caused by a traffic accident. Two months later, a hematoma developed at the site of drainage in the left chest, and blood coagulation tests revealed prolongation of the aPTT, which had been normal on admission. Plasma factor VIII procoagulant activities in cases 1, 2 and 3 were 3%, 1% and 5%, respectively. The respective factor VIII inhibitor titers were 78, 870 and 0.5 Bethesda units/ml. The immunoglobulin class and subclass of the inhibitors examined by an ELISA method were: case 1, IgG1 and 4; case 2, IgG2 and 4 (dominant); case 3, IgG4. In cases 1 and 3, the patients recovered after glucocorticoid therapy, but in case 2 the patient died of intraperitoneal hemorrhage despite receiving two courses of methylprednisolone pulse therapy. The above clinical experience suggests that patients, who develop high titers of inhibitors may be refractory to ordinary immunosuppressive therapy, and therefore more aggressive therapy such as plasma exchange and/or bypass therapy using activated prothrombin complex concentrates or an activated factor VII preparation should be considered. PMID- 11193440 TI - [An autopsy case of pulmonary mucormycosis with fatal hemoptysis from a rupture of the thoracic descending aorta during remission from acute myelocytic leukemia]. AB - A 16-year-old girl was hospitalized because of anemia and thrombocytopenia in April 1998, and was diagnosed as having AML (FAB:M2). After failure of initial remission induction therapy, she was successfully treated with the MEC regimen as a second-line chemotherapy. On June 22, the first consolidation therapy was started. One week later, the patient developed a high fever with backache. Chest computed tomography (CT) on July 8 showed a 3cm mass lesion adjacent to the thoracic descending aorta in the left upper lobe. She was given fluconazole and antibiotics, and remained in remission. On July 24, the mass lesion changed to a cavitary lesion on chest CT, suggesting a fungal infection, probably aspergillosis. With recovery from neutropenia, the patient became asymptomatic, and fluconazole was changed to itraconazole. On July 27, she suffered sudden, massive hemoptysis and died. Autopsy revealed a localized adhesion between the cavitary lesion and the thoracic descending aorta, and the aortic wall was ruptured at this site. Microscopic examination revealed invasion of mucormycotic hyphae into the wall of the aorta with infiltration of inflammatory cells. The vasa vasorum were occluded by thrombi, in which mucormycotic hyphae were detected. PMID- 11193441 TI - [Lymphocytic infundibuloneurohypophysitis during the first remission in acute lymphoblastic leukemia]. AB - A 15-year-old girl developed acute lymphoblastic leukemia (ALL). The patient was treated according to the 13th protocol of the Tokyo Children's Cancer Study Group, and thereafter remained free of disease. However, at the age of 20, she complained of polyuria, polydipsia and amenorrhea. Hematological or meningeal relapse was ruled out on the basis of clinical and laboratory findings. The plasma concentrations of GH, TSH, LH, FSH, ACTH and ADH were low or below the detectable limits. There was no increase in urine osmolarity after water deprivation. Arginine, LH-RH, TRH and CRH tolerance tests revealed no or low responses of GH, LH/FSH, TSH, and ACTH/cortisol, respectively. Magnetic resonance imaging demonstrated thickening of the pituitary stalk, which was homogeneously enhanced by gadolinium administration. A biopsy specimen showed fibrosis and infiltration of CD8-positive T lymphocytes in a portion of the pituitary stalk, whereas the adenohypophysis was normal. In addition, no leukemic cells were observed in the samples. Thus, a diagnosis of lymphocytic infundibuloneurohyophysitis (LIN) was established. All the symptoms were improved by treatment with hydrocortisone, L-thyroxine, desamino-8-d-arginine vasopressin, estrogen and gestagen. This is the first reported case of ALL complicated by LIN. PMID- 11193442 TI - [Anhidrosis during long-term hydroxyurea therapy in a patient with chronic myelogenous leukemia]. AB - A 62-year-old man was diagnosed as being in the chronic phase of chronic myelogenous leukemia (CML) in 1990, and subsequently treated with hydroxyurea (HU). The total HU dose administered reached 2,929 g (average, 1.44 g/day). In December 1995, the patient was admitted to our hospital for control of the CML. Following HU therapy, he often experienced high fever (38-39 degrees C) due to infection or blastosis, and at that time his skin showed marked pigmentation, dryness and scaling with itching and anhidrosis. A skin biopsy sample from the left scapula showed atrophic change of the skin and epidermal tissues with fibrotic changes and damage to the subcutaneous glands. This was strongly suspected to have been caused by the continuous HU administration, and the anhidrosis and dryness was considered to have contributed to the patient's high body temperature. Frequent cooling of the patient's body was effective. PMID- 11193443 TI - [Clinical significance of a multiple myeloma cell line, derived from a case associated with hyperammonemia]. AB - Recently, there have been several reports describing patients with multiple myeloma complicated by consciousness disturbance due to hyperammonemia. Here we report a patient with multiple myeloma and hyperammonemia, who died after rapid progression of the disease. A 71-year-old man who had been diagnosed as having Bence Jones protein (kappa)-type multiple myeloma in 1996 was readmitted to our hospital in February 1997 because of worsening bone pain, renal dysfunction, and hypercalcemia. Bone marrow aspiration yielded an almost dry tap, and the bone marrow was found to be completely occupied by immature plasma cells. Although liver dysfunction was slight, the serum ammonia level was high and increased gradually. Despite treatment, the patient died due to cerebral embolism and progression of plasmacytic leukemia in October 1997. Peripheral blood sampled at the time of death showed a serum ammonia level of 204 micrograms/dl, and the myeloma calls were cultured using monolayered bone marrow stromal cells as feeder cells. This led to the successful establishment of a cell line. The level of ammonia in the supernatant was high, indicating that the cultured myeloma cells produced and released ammonia. PMID- 11193444 TI - [Recovery from pancytopenia and liver dysfunction after administration of thiamazole for hyperthyroidism]. AB - A 45-year-old woman was referred to our hospital because of hyperthyroidism complicated by atrial fibrillation and heart failure. Laboratory data revealed pancytopenia, with a white blood cell count of 2,600/microliter, red blood cell count of 330 x 10(4)/microliter, and platelet count of 6.2 x 10(4)/microliter. The patient had normal transaminase levels, but tests for hepaplastin and cholinesterase showed values of 34% and 1.4 U/ml, respectively, indicating liver dysfunction. There was also decreased excretion of indocyanine green. After initiation of treatment with 30 mg thiamazole and 20 mg propranolol daily, the patient's thyroid function normalized and the other abnormal laboratory findings such as pancytopenia and liver dysfunction also disappeared. Pancytopenia is a rare complication of hyperthyroidism. In this case, various laboratory abnormalities were normalized by antithyroid therapy alone, indicating that the hyperthyroidism itself was closely related to the pathogenesis of pancytopenia and liver dysfunction. PMID- 11193445 TI - [Severe hemolysis and SIADH-like symptoms induced by vincristine in an ALL patient with liver cirrhosis]. AB - An 11-year-old boy was diagnosed as having acute lymphoblastic leukemia (ALL, L1) in 1987 and underwent treatment with an ALL high-risk protocol (prednisolone, vincristine (VCR), daunorubicin, 1-asparaginase), which resulted in complete remission. In 1990 he developed chronic hepatitis C and received interferon therapy. In December 1994, ALL recurred, and the patient was treated with VCR. He subsequently developed severe hemolysis (Hb 12.5 g/dl-->6.8 g/dl) with increases of indirect bilirubin, AST, and LDH. Furthermore, symptoms resembling a syndrome of inappropriate secretion of ADH (SIADH) and DIC developed. Upon incubation of the patient's red blood cells with VCR in vitro, extreme deformity of the cells was observed. These findings suggested that splenomegaly, due to liver cirrhosis which had developed rapidly from chronic hepatitis C while the patient was in an immunosuppressed state induced by anticancer drugs, had trapped the deformed red blood cells and resulted in severe hemolysis. The patient died on the 165th day after admission due to liver failure. PMID- 11193446 TI - [Usefulness of early tetrofosmin myocardial SPECT during subacute period to estimate salvaged myocardium in patients with acute myocardial infarction- comparing with tetrofosmin myocardial SPECT during chronic period and evaluating regional wall motion using QGS method]. AB - To evaluate salvaged myocardium of acute myocardial infarction (AMI), we performed rest 99mTc-tetrofosmin (TF) SPECT with rest Tl and Tc-pyrophosphate (PYP) dual SPECT within 10 days after admission in 19 patients with initial AMI, who all were reperfused successfully and without restenosis. TF SPECT was obtained at 15 minutes (E) after tracer injection, 4 hours later (D), and 5 months later (FU). We calculated the regional uptake score (RUS) of infarcted area estimated by Tc-PYP uptake and defined RUS(FU) of TF(FU) as salvaged myocardium, and then regarded RUS/RUS(FU) x 100 (%) as subacute predicted value of salvaged myocardium. Furthermore, we regarded the improvement of wall motion estimated by QGS method as the guidepost of myocardial viability. The subacute predicted value of TF(E) was 85 +/- 25%, which was significantly higher than 61 +/- 28% of Tl and 36 +/- 24% of TF(D) (p < 0.01). Sensitivity and specificity of myocardial viability based on the improvement of wall motion SPECT image were 78% and 73% for Tl, 90% and 87% for TF(E) and 52% and 87% for TF(D). TF myocardial early imaging in subacute period was useful to detect salvaged myocardium. PMID- 11193447 TI - [Coronary flow reserve evaluated by 201Tl myocardial perfusion SPECT after coronary artery bypass grafting (CABG) for angina pectoris]. AB - We compared the flow reserves of the coronary bypass vessels between arterial and venous grafts by 201Tl myocardial perfusion SPECT on the patients with angina pectoris who had no past history of myocardial infarction or intervention therapy such as PTCA. Thirty two patients had undergone a total of 70 bypass grafts and 66 of them were proved to be patent at postoperative CAG. Reversible defects were observed in 6 of 40 segments (15.0%) covered by patent venous grafts, and in 11 of 26 segments (42.3%) by patent arterial grafts. The rate of postoperative reversible defects was higher in the areas grafted by artery but this had no relation with the severity of coronary artery stenosis before CABG. This reversible defect is most likely to be caused by the character of artery graft itself and this should not be considered to highly suggest the restenosis or occlusion of the graft vessel. PMID- 11193448 TI - [A new method for pharmacokinetic analysis of 99mTc-GSA using two-compartment and two-parameter model]. AB - Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (99mTc-GSA) is a liver scintigraphy agent which binds to asialoglycoprotein receptor in hepatocyte. Twenty-six patients with liver dysfunction were examined with 99mTc-GSA liver scintigraphy using two-compartment and two-parameter model (2C2P model). The 99mTc-GSA was assumed to move within two compartments (whole blood and liver). k1 and k2 were parameters which represented transfer rate constant from blood to liver, and from liver to blood, respectively. Two differential equations based on 2C2P model were integrated, so that k1, k2, k1/k2 and VLmg were estimated from the time-activity curves of the heart and liver. VLmg was computed as maximum amount of 99mTc-GSA binding to liver. The results were compared with the liver function tests and the conventional 99mTc-GSA indices: HH15, LHL15, and LU15. k1/k2 and VLmg values had positive correlation with the result of the serum liver function tests, Plt., T.Bil., ChE, GOT, LDH, ALP and gamma GTP. It is concluded that this new method using 2C2P model is not invasive and simplest in the 99mTc-GSA liver scintigraphies, and may be useful in evaluating liver function. PMID- 11193449 TI - [99mTc-HMDP accumulation in soft tissue tumor]. AB - Accumulation with bone scintigraphy using technetium-99m hydroxymethylene diphosphonate (99mTc-HMDP) in 68 cases with radiographically or pathologically verified soft tissue tumor was examined. Radiographical or histopathologic diagnoses of the 68 cases included; 14 lipomas, 11 liposarcomas, 11 neurinomas or neurofibromas, 6 malignant lymphomas, 5 malignant fibrous histiocytomas, 5 hemangioma, rhabdomyosarcomas, 2 Langerhans cell histiocytoses, 2 desmoid tumors and one each of neuroblastoma, hemangiopericytoma, angiomyxoma, plasmacytoma, liomyosarcoma, lymphangioma, fibrosarcoma, elastofibroma, synovial sarcoma, and ganglion. Thirty-seven (54%) showed positive accumulation and 31 were negative. One half of soft tissue tumors can be accumulated by 99mTc-HMDP. PMID- 11193450 TI - [Electrocardiographic findings in pulmonary thromboembolism--comparison with lung perfusion scan and echocardiographic findings]. AB - This study investigated the usefulness of electrocardiography (ECG) in pulmonary thromboembolism (PTE), compared with lung perfusion scan and echocardigraphic findings on evaluation of the severity. We checked ECG findings associated with PTE at hospital admission, with the seven abnormal findings described by Sreeram N, et al. On Lung perfusion scan, severity of perfusion defect was assessed total defect score (TDS), calculated as the sum of the scores for all 18 segment of lung. On echocardiography, severity of right ventricular overload was assessed. The number of the seven ECG abnormal findings and TDS were larger in patients with the right ventricular overload (p < 0.01). The number of the ECG findings was positively correlated with TDS (r = 0.75). The number of abnormal ECG findings in PTE is associated with the severity evaluated by lung perfusion scan and echocardiography. PMID- 11193451 TI - [Regional assessment of treatment in lung cancer using lung perfusion and ventilation images]. AB - In 30 patients with lung cancer undergoing non-surgical treatment, we performed perfusion lung imaging using 99mTc-MAA and inhalation lung studies using Technegas before and after treatment and evaluated regional perfusion and ventilation status in the lung regions where bronchogenic carcinoma was located. Regional ventilation status was preserved rather than perfusion counterpart (V > P) in 18 patients (18/30 = 60.0%) before treatment, while the former was better than the latter in 27 patients (27/30 = 90.0%) after treatment, indicating that regional ventilation status improved more significantly than regional perfusion counterpart after treatment (p = 0.005). We also classified the therapeutic effect for regional perfusion and ventilation status as improved, unchanged, or worsened, respectively; improvement in regional perfusion status was observed in 17 patients (56.7%) and that in regional ventilation status in 24 patients (80.0%). There was a statistically significant correlation between improved regional perfusion and ventilation status (p = 0.0018) when therapeutic effect was recognized. The patients who showed improvement in regional perfusion status after treatment always showed improved regional ventilation status, but 7 patients showed either unchanged or worsened regional perfusion status after treatment, although regional ventilation status was improved. In conclusion the pulmonary vascular beds seem more vulnerable to bronchogenic carcinoma and improvement in regional perfusion status was revealed to be more difficult than that in regional ventilation status after treatment. PMID- 11193452 TI - [Results of radioiodine therapy in patients with pulmonary metastases of differentiated thyroid cancer]. AB - Factors affecting the effect of 131I treatment and survival after pulmonary metastases in patients with differentiated thyroid cancer, were studied. Between 1984-1999, pulmonary metastases was observed in 51 out of 153 patients with differentiated thyroid cancer at our institution. Of these 41 patients had papillary and 10 follicular thyroid cancer. There were 37 females and 14 males with mean age (+/- S.D.) of 50.5 +/- 19.0 years. These 51 patients were subjected to 131I therapy. The effect of 131I treatment and the prognostic values of the following variables were examined: sex, age at the time of 131I treatment, histologic type of cancer, size of pulmonary metastases on CT, total-body scintigraphy with 201Tl and 131I, serum thyroglobulin levels and presence of metastases in distant sites other than lung. The effect of 131I treatment was evaluated by means of changes in the number and size of metastatic shadows on chest CT and by serum thyroglobulin levels. The minimum duration of follow-up was 12 months. Therapeutic 131I dose scans revealed detectable uptake in 25 of 51 patients. Therapeutic 131I dose uptake was achieved more frequently in patients under 40 years of age and in those with follicular cancers. Of the 51 patients, 13 were evaluated to be treated successfully. Those under 40 years of age, with 131I uptake in the lung and presence of other metastases showed a good response to treatment than others. Follicular cancer showed a more significant association with coarse type of lung metastases (> 5 mm in diameter on chest CT) and good 131I uptake than papillary cancer. Of all the variables studied, the best prognosis for survival was demonstrated by increased 131I uptake in pulmonary metastases. These results indicate that age, 131I uptake and presence of other metastases are important factors in predicting the effect of 131I treatment for pulmonary metastases of differentiated thyroid cancer. PMID- 11193453 TI - [The usefulness of 99mTc-MIBI scintigraphy in a patient with hyperparathyroidism who underwent percutaneous ethanol injection therapy]. AB - 99mTc-MIBI scintigraphy was performed in a 67-year-old male with hyperparathyroidism who underwent percutaneous ethanol injection therapy (PEIT). Abnormal 99mTc-MIBI uptake was clearly recognized. 99mTc-MIBI scintigraphy was useful also in the evaluation of hyperparathyroidism after imperfect PEIT. PMID- 11193454 TI - [A case of bone metastases from carcinoma of the lung demonstrating increased uptake of 99mTc-ECD]. AB - A 48-year-old man with carcinoma of the lung had loss of consciousness during radiation therapy and underwent 99mTc-ethyl cysteinate dimer (99mTc-ECD) SPECT to evaluate brain tumor seen on CT scan. Incidentally 99mTc-ECD SPECT imaging showed intense accumulation in the frontal and occipital bone. The tumor in the occipital bone had been histologically proven to be a metastasis from carcinoma of the lung. We presented a very rare case of bone metastasis demonstrating increased uptake of 99mTc-ECD. PMID- 11193455 TI - [Allergic rhinitis in the new millennium]. PMID- 11193456 TI - [Food allergy and food components]. PMID- 11193457 TI - [Japanese guideline for treatment and management of childhood asthma]. PMID- 11193458 TI - [A study of food-dependent exercise-induced anaphylaxis by analyzing the Japanese cases reported in the literature]. AB - We surveyed and analyzed cases of food-dependent exercise-induced anaphylaxis (FDEIA) in the Japanese literature. We found 167 cases which were reported as FDEIA since 1983. Analyzing these case, following characteristic features were revealed: 1) Recent upward trend in the number of reports of FDEIA was noted. 2) Male cases were more frequent than female cases, while about half of the cases were teenager. 3) More than half of the cases were proved to be induced by wheat followed by shrimp. In those under 20, shrimp was the most popular cause rather than wheat. 4) Skin test and/or IgE RAST showed positive results in most cases, suggesting that the response itself is linked to type I allergic reaction. 5) About 40% of the patients had history of atopic disease, indicating that atopic condition may play some role in FDEIA. 6) All cases who performed provocation test with aspirin responded to food challenge and/or exercise in combination with aspirin. This indicates that aspirin plays a key provoking factor in FDEIA. 7) In 17 cases FDEIA attacks were observed during noon recess or physical education class after lunch at school. We stress here the importance of a nation-wide education to school teachers the potential danger of this disorder. PMID- 11193459 TI - [Change in skin reactivity to common allergens in allergic patients over a 30 year period. Association with aeroallergen load]. AB - Five-year changes in the percentage of positive intradermal test to allergens in patients with bronchial asthma (BA) and allergic rhinitis (AR) over a period of 30 years from 1969 to 1998 were analyzed, with consideration of their association with the yearly changes in the levels of airborne pollens and molds over 30 years. Allergens used throughout the period were house dust, pollens from various plants (Japanese cedar, pine, oak, Japanese alder, Zelkova, orchard grass, ragweed, mugwort and Japanese hop) and molds (Alternaria, Cladosporium, Aspergillus, Penicillium and Candida). Overall percentages to house dust were higher in BA patients than in AR patients, but those to pollens were distinctly higher in the latter. Those to molds were higher in BA patients, except that those to Alternaria were about the same in both BA and AR patients. Therefore, the clinical expression of allergy may differ according to the type of allergen to which subjects are sensitized. Over the course of 30 years, the increase in the percentage of positive intradermal test to all of the allergens used was noted in both BA and AR patients, although this did not always reflect the aeroallergen load. This includes the two extremes to pollens from Japanese cedar and pine, either of which is the most common source of allergen in Japan. Significant increases in the percentages to Japanese cedar pollen (from 12.5% to 54.4% in BA patients, and from 35.1% to 81.5% in AR patients) appeared to be roughly correlated to marked increases in pollen count. In contrast, that to pine pollen was kept low at about 2%, because of their weak allergenicity, but abruptly increased to 5-6% in the last decade, despite the almost invariable pollen count over the last 30 years. Therefore, the increased sensitivity to aeroallergens may also be associated with other factors besides their load in the air. PMID- 11193460 TI - [Atopic dermatitis in early infancy in Matuyama city: prevalence and seasonal variations]. AB - From Jun 1996 to May 1999, 1280 infants were examined by the author 6 times from birth to 12 month-old in each 0, 1, 3, 6, 9, 12 month-old time at NTT Nishinihon Matuyama Hospital. The 12-month cumulative prevalence of AD was 28.5%. Out of the cases 82.2% showed the symptoms before 3 month-old. There were 217 male infants in AD group (59.5%). This percentage was significantly higher than 45.2% in non AD group (p < 0.001). Approximately 70% cases in AD group had family history of allergic diseases. This ratio was significantly higher compared to 49.6% in non AD group (p < 0.001). According to the season of birth, there were significant differences in the 12-month cumulative prevalence of AD (p < 0.005). Infants born in the spring, summer, autumn and winter showed 21.1%, 27.2%, 31.3%, and 33.9% of cumulative prevalence of AD respectively. The prevalence of AD at 3 month-old and the ratio that the symptoms appeared before 3 month-old also had similarly significant tendency (p < 0.001) (Infants born in the spring showed 15.4% and 73%. Infants born in the winter showed 31.5% and 92.9%). There were no relationship between the cumulative prevalence of AD and the precipitation. PMID- 11193461 TI - [Relation between serum eosinophil cationic protein (ECP) level and asthma attack in children]. AB - Serum eosinophil cationic protein (sECP) levels were measured in 339 patients with childhood asthma, and the clinical courses of these patients were followed for 57 weeks. While considering the history and characteristics of each patient, we examined the correlation between asthma attack frequency and sECP, blood eosinophil count, and serum total IgE (tIgE) to determine their usefulness in predicting asthma attacks. Among patients with no other allergic diseases, sECP levels in patients who had no asthma attacks two weeks before or after the measurement were significantly lower than those of patients who had attacks during the same four-week period. Among patients who had attacks, those patients with no attack for a year after the measurement were also found to have low sECP levels. Similarly, even among patients with asthma attacks and high sECP levels, there were cases where attacks were well controlled using nebulizer treatments with DSCG or BDP. The incident rate of attacks for patients with other allergic diseases and a low sECP was low. Yet, there was no common trend in patients with high sECP levels. Moreover, this study detected a significant correlation between sECP level and blood eosinophil count as well as between sECP level and serum tIgE. The most significant correlation with asthma attack frequency was sECP level. Thus, sECP level seems to reflect the allergy activity level, especially two weeks prior to and after the measurement. For patients without other allergic diseases, asthma attack prediction during the two weeks period after the measurement of sECP also seems possible. Therefore, periodic measurement of sECP level is useful in objectively monitoring the improvement of symptoms and establishing the treatment plan, including treatment with DSCG or BDP. PMID- 11193462 TI - [A clinical case of 13 years old boy of aspirin-induced asthma with food allergy]. PMID- 11193463 TI - [A new spacer, Babyhaler, for BDP inhalation therapy in severe infantile asthma]. AB - Recently, it has been recognized that airway inflammation is the most important pathogenesis of bronchial asthma, and inhaled corticosteroids therapy is effective for childhood asthma. However, using metered dose inhalers (MDI) of beclomethasone dipropionate (BDP) is difficult for infants. In this study, we administered BDP inhalation therapy with a new spacer, Babyhaler, for five cases of early childhood with severe infantile asthma that we could not control even by combination of theophylline round the clock (RTC) therapy and disodium cromoglycate (DSCG) + beta 2 stimulant (beta 2) regular use. We compared symptom score of asthma attack between the pre-treatment period (prior 2 weeks) and post treatment period (following 8 weeks) of BDP inhalation therapy with Babyhaler. As a result, symptom score decreased significantly within 4 weeks after treatment of BDP with Babyhaler as compared with the score before treatment of BDP. These findings suggest that Babyhaler is useful for BDP inhalation therapy in infantile asthma. PMID- 11193464 TI - [Study on casein allergy in children]. AB - Casein a component of milk is used for food additives, industrial materials and drugs. However casein is known to be a main allergen in milk allergy. Recently several cases of anaphylaxis to antibiotics including casein have been reported. In this study we investigated casein allergy in milk allergy. 6 out of 8 patients who were positive for milk RAST were also positive for casein RAST. In these positive cases only 3 out of 6 patients had some allergic symptoms after taking antibiotics. In 3 patients DLST was also positive to casein. There was one patient who was positive in DLST without any symptoms after taking the same antibiotics. It is needed to pay attention to casein allergy when giving the medication which includes casein. PMID- 11193465 TI - 5th Congress of the European Federation of Neurological Societies. 14-18 October 2000. Copenhagen, Denmark. Abstracts. PMID- 11193468 TI - Gastric polyps: an update of their pathology and biological significance. AB - Gastric polyps are clinically important lesions that are frequently encountered in routine pathology (2-3% of all gastroscopies). Polyps may occur sporadically or in polyposis syndromes, such as familial adenomatous polyposis coli (FAP), Peutz-Jeghers syndrome, juvenile polyposis, Cowden's disease and Cronkhite-Canada syndrome. In biopsy specimens taken during routine gastroscopic examinations, it is almost always possible to differentiate between neoplastic and non-neoplastic polyps and to type polyps. In this review, we focus on the morphological spectrum of gastric polyps in an attempt to assist the pathologist and the gastroenterologist in recognising the lesion and in treating patients with gastric polyps, respectively. Further, we propose that the World Health Organization (WHO) classification should be modified to include the following categories: non-neoplastic polyps (WHO: tumour-like lesion), hamartomatous polyps/polyps of polyposis syndromes (WHO: tumour-like lesion), heterotopic tissue polyps (WHO: tumour-like lesion), neoplastic polyps (WHO: epithelial, non epithelial and endocrine tumours) and reactive polypoid lesions. PMID- 11193469 TI - Mantle cell lymphoma, in leukaemic phase with prominent splenomegaly. A report of eight cases with similar clinical presentation and aggressive outcome. AB - Mantle cell lymphoma (MCL) is a well-defined peripheral B-cell lymphoma usually diagnosed upon peripheral lymph node biopsy. We report eight cases of peripheral B-cell leukaemia that demonstrate presumptive evidence of mantle cell characteristics. The patients had a median age of 68.5 years, and five were male. All presented with an enlarged spleen without any peripheral lymphadenopathies, and they were leukaemic at presentation (median lymphocytosis, 38x10(9)/l). Morphological diagnosis of MCL was very difficult in five cases but easier in three because we were able to analyse either pre- or post-mortem lymph nodes and spleen. The immunophenotype of blood lymphocytosis using flow cytometry, the presence of a t(11;14)(q13;q32) and a cyclin D1 expression by leukaemic cells all fit with the diagnosis of MCL. All patients progressed and died with a median overall survival of 8 months. Multifocal areas of transformation in blastoid or large cell variants were observed in the three autopsied patients. In summary, one should consider the diagnosis of MCL at presentation in leukaemic phase even in the absence of peripheral adenopathies. PMID- 11193470 TI - beta-catenin expression pattern in primary oesophageal squamous cell carcinoma. Relationship with clinicopathologic features and clinical outcome. AB - beta-Catenin has an essential role in intercellular adhesion and signal transduction. beta-catenin functions as a transcriptional activator downstream in the Wnt signalling pathway. Cytoplasmic stabilisation of beta-catenin, mainly due to inactivating mutations of the adenomatous polyposis coli (APC) tumour suppressor gene or activating mutations in exon 3 of the beta-catenin gene, can activate this important pathway in the development of several carcinomas. To determine whether this pathway for malignant transformation is important in oesophageal cancer, we analysed 39 primary oesophageal squamous cell carcinomas (OSCC). Immunohistochemical expression of beta-catenin was studied in formalin fixed, paraffin-embedded tissue samples. Results were correlated with clinicopathological parameters and immunohistochemical expression of the proteins p53, E-cadherin, bcl-2 and Ki-67. All examined OSCC had beta-catenin expression localised in the cellular membrane, frequently with a heterogeneous pattern. Seven (18%) cases also showed immunoexpression in the cytoplasm and nuclei of the tumour cells. These seven tumours were localised in the upper (three) or in the middle third (four) of the oesophagus. Only one patient had p53 expression and all had bcl-2 expression. The consensus sequence for glycogen synthase kinase (GSK) 3beta phosphorylation in exon 3 of the beta-catenin gene was studied using polymerase chain reaction and direct sequencing in the seven cases with nuclear beta-catenin expression. No genetic alteration was found. These results suggest that beta-catenin expression may characterise a subset of OSCC. PMID- 11193471 TI - Comparison of loss of heterozygosity and microsatellite instability in adenocarcinomas of the distal esophagus and proximal stomach. AB - Adenocarcinoma of the gastroesophageal junction is rapidly rising in incidence. It has been proposed that these tumors be classified as three different types: distal esophageal (AEG I), cardia (AEG II), and subcardia (AEG III). Using comparative genomic hybridization (CGH) analysis, one recent study reported that the 14q chromosomal arm showed a significantly higher rate of deletion in esophageal than in cardia adenocarcinoma. Using a microsatellite analysis technique, we analyzed this area and regions in the vicinity of the APC, DCC, and p53 genes. Tumor and normal tissues were microdissected from 54 cases (27 AEG I and 27 AEG III). DNA was extracted and then amplified using seven fluorescent labeled microsatellite markers, one pair each on 5q, 18q, and 17p and four on 14q. The results were analyzed for loss of heterozygosity (LOH) and microsatellite instability (MSI). LOH varied from 20% to 30% at each locus except for the 17p locus, where it was slightly above 50% in both groups. No significant differences in LOH or MSI were found between the esophageal and gastric tumors, including the 14q chromosomal arm. These results fail to confirm the finding that abnormalities on the 14q chromosomal arm distinguish between distal esophageal and proximal gastric tumors. PMID- 11193472 TI - Assessment of tumor angiogenesis in invasive breast carcinomas: absence of correlation with prognosis and pathological factors. AB - Different retrospective studies have shown that microvessel counting (MVC) is an independent prognostic marker for clinical outcome in breast cancer. The aim of this study was to evaluate the prognostic value of MVC alone or in association with classical clinicopathological parameters, as well as the reproducibility of the technique. We analyzed a retrospective series of 216 cases of breast carcinoma. Tissue sections were stained for Factor-VIII-related antigen. Microvessel quantification was performed at x400 magnification in the three most vascular areas of the tumors (hot spots). Mean and highest values were studied. Furthermore, a semi-quantitative evaluation of MVC was performed by use of an image-analysis system. The effect of multiple factors on survival was tested under a Cox multivariate proportional hazards model. In ten cases, a study of the reproducibility was done by evaluating MVC in different sections of the same block and in different blocks of a same tumor. There was no association between MVC (determined at a microscopic level or by image analysis) and overall survival or relapse-free survival. No association was found with tumor size, tumor grade, and lymph-node status. The study of reproducibility showed a very high intra tumoral variation of MVC. The intra-individual coefficient of variation (CV) varied between 20 and 80%. This study did not show any significant correlation between angiogenesis, as assessed by MVC, and relapse-free survival or overall survival in infiltrating breast carcinomas. The low reproducibility of the MVC for the same tumors suggests that this technique must still be optimized before routine application. PMID- 11193473 TI - Stromelysin-3 expression in invasive ovarian carcinomas and tumours of low malignant potential. AB - Stromelysin (ST)-3 is considered to be a marker of invasion and preinvasive lesions to indicate the likelihood of subsequent invasion. The expression of ST-3 has not been systematically studied in ovarian neoplasms. We studied 47 ovarian carcinomas and 49 ovarian tumours of low malignant potential (LMP) to see whether the expression of ST-3 correlated with any histopathologic features and, in the LMP tumours, whether its expression might be a prognostic indicator. All of the primary tumours and available metastases or implants were studied using immunohistochemistry (IHC) for ST-3 and, in 52 selected lesions, in situ hybridisation (ISH) using a cDNA probe. Expression of ST-3 was seen in 42 of 47 (89%) of the carcinomas and in 16 of 49 (33%) of the LMP cases. A significantly higher percentage of carcinomas than LMP tumours (P<0.00001) expressed ST-3 in the stroma adjacent to the tumour, with a correlation to increasing FIGO (International Federation of Gynecology and Obstetrics) tumour stage. ST-3 was expressed in the surrounding stroma of 1 of 8 LMP implants and 46 of 55 (84%) of the carcinoma metastases. The single LMP patient who died of tumour recurrence had ST-3 expression, but a significant prognostic impact was not found. The infrequent expression of ST-3 in LMP compared with carcinoma metastases appears to be more consistent with a peritoneal "field effect" than spread from the ovarian LMP tumour. PMID- 11193474 TI - Nuclear changes in the normal-looking columnar epithelium adjacent to and distant from prostatic intraepithelial neoplasia and prostate cancer. Morphometric analysis in whole-mount sections. AB - Subtle morphological changes and molecular alterations have been reported in normal-appearing tissue in prostates with high-grade prostatic intraepithelial neoplasia (PIN) and prostate cancer (PCa). The severity and the distribution of these changes and alterations within the prostate gland have not been addressed in previous publications. The aim of this study was to investigate morphometrically the nuclear changes of the normal-looking columnar epithelium adjacent to and distant from high-grade PIN and PCa. Karyometry was performed on the whole-mount histological sections of three radical prostatectomy (RP) specimens. Two concentrical lines, one corresponding to the outer surface (or capsule) of the prostate and the other corresponding to one centimeter towards the center, were drawn with a black pen on each whole-mount section. The part of the prostate tissue between these two boundaries was then divided into twelve equal sectors or regions. The part within the inner line was divided into two regions. The analysis was also performed on the slides of the apex and base of the prostate. One prostate contained normal-looking epithelium only (case no. 1). Another contained both high-grade PIN and PCa, the former occupying larger areas than the latter (case no. 2). Both high-grade PIN and PCa were present in the third sample, in which PCa was more widely distributed than PIN (case no. 3). The lesion measured in each region was always the most severe, e.g., either high grade PIN or PCa. When neither were identifiable, then the normal-looking columnar epithelium was analyzed. For each sector, the mean and standard deviation of the nuclear area, maximum nuclear diameter, nuclear roundness factor, and nucleolar area were calculated. In normal-looking columnar epithelium, the mean of the mean nuclear area of the sectors of case no. 1 was 35.19 microm2 (SD 4.14). The mean nuclear areas in cases no. 2 and no. 3 were 37.94 microm2 (SD 4.65) and 37.31 microm2 (SD 4.36), respectively. The mean of the mean nuclear area of the sectors with high-grade PIN of case no. 2 was 49.85 microm2 (SD 8.44), whereas it was 54.26 microm2 (SD 2.91) in case no. 3. The mean of the nuclear area values obtained in the sectors of cases no. 2 and no. 3 with PCa was 56.74 microm2 (SD 6.56) and 61.17 microm2 (SD 8.13), respectively. When considering the normal-looking tissue of the second and third case, 79% and 90%, respectively, of the regions showed nuclear area values greater than 34.94 microm2 (e.g., the 50th percentile of the mean nuclear area values of the regions of the first case). Sectors with normal-looking epithelium, whose nuclear area was above this threshold, were both adjacent to and at a distance of more than 1 cm from those with PIN or PCa. The other nuclear features showed a similar trend of value changes. This study demonstrates that the normal-looking ducts and acini from prostate harboring preneoplastic and neoplastic lesions show morphological nuclear abnormalities that are not seen by the human eyes but that can be detected with image analysis. Such changes may be of diagnostic importance, especially in cases where clinical suspicion for cancer prevails after a negative biopsy. PMID- 11193475 TI - Thyroglobulin mRNA expression helps to distinguish anaplastic carcinoma from angiosarcoma of the thyroid. AB - The existence of angiosarcoma (AS) of the thyroid has been a matter of debate for many years, because some authors believe that most if not all ASs are in fact "angiomatoid" anaplastic carcinomas (ACs). Immunohistochemistry alone was not successful in solving the problem, since cytokeratin expression is a known occurrence in AS. Therefore, we wanted to compare nine cases of AS with ten cases of AC, assessing whether thyroglobulin (TG) mRNA was still transcribed in undifferentiated tumors and could be helpful to distinguish AC from AS. The cases were analyzed for TG mRNA expression by means of radioactive in situ hybridization. The silver grains were counted using an automated device, and their amount was compared with that of stroma, background, and peritumoral thyroid. A weak signal was present in all AC but not in AS (mean counts 35.7 and 9.6 arbitrary units, respectively: P<0.01). In two cases of AC, residual areas of poorly differentiated insular carcinoma had a strong signal (similar to that of peritumoral thyroid). These findings further confirm that AC and AS of the thyroid are unrelated malignant tumors. PMID- 11193476 TI - Two cases of ectopic hamartomatous thymoma. AB - Ectopic hamartomatous thymoma (EHT) is a rare benign neoplasm. Since it was named by Rosai et al. in 1984, 24 cases have been reported. We herein report two cases of EHT, one of which presented with massive myoid cells, and review the literature related to EHT. Both of our cases displayed the typical features of EHT: (1) nests of epithelial cells, including solid, cystic, or glandular epithelial islands; (2) spindle cells dominating the microscopic picture; and (3) adipose cells which intermingle haphazardly to impart a hamartomatous quality to the tumor. In this paper, we observed massive myoid cells and the transition from spindle epithelial cell to myoid cell in one of our cases. Immunohistochemical examinations showed that the main component of EHT, spindle cells, was positive for cytokeratin and epithelial membrane antigen (EMA). Intriguingly, the myoid cells simultaneously expressed cytokeratin, EMA, myoglobin, and creatine kinase mm, suggesting that myoid cells may originate from epithelial cells and are an intermediate state between epithelial cells and muscular cells. PMID- 11193477 TI - Proliferation and number of Clara cell 10-kDa protein (CC10)-reactive epithelial cells and basal cells in normal, hyperplastic and metaplastic bronchial mucosa. AB - Clara cell 10-kDa protein (CC10) is an inhibitor of phospholipase A2 and binds to phosphatidylinositol. It may therefore interfere with intracellular signal transduction. Bronchial CC10-reactive cells have been described by several authors. In contrast to the bronchiolar CC10-containing Clara cell, which is a progenitor cell of terminally differentiated airway epithelium, the role of bronchial CC10-reactive cells remains to be elucidated. We assessed the number of bronchial CC10-reactive cells in relation to cytokeratin (CK) expression and proliferative activity in normal, hyperplastic and squamous metaplastic epithelium. Sixty-five human bronchial mucosal specimens were investigated immunohistochemically for CK expression (CK7, CK13 and CK5/6), proliferative activity (MIB-1) and number of CC10-reactive epithelia. The proliferation fraction of CC10-reactive cells was assessed with double staining for MIB-1 and CC10. The proliferation index of the epithelium differed significantly between normal, hyperplastic and metaplastic epithelium. The number of CC10-reactive cells was inversely related to the epithelial proliferation. Bronchial CC10 reactive cells showed no proliferative activity as assessed using immunohistochemical double staining for CC10 and MIB-1. In contrast to normal and hyperplastic epithelium, squamous metaplasia disclosed CK5/6 in all epithelial layers, a loss of CK7 and a gain of CK13. We conclude that CC10-reactive cells have no progenitor role in the bronchial mucosa. However, because the proliferative activity is inversely related to the number of CC10-reactive cells, the CC10 protein may play a role in the regulation of epithelial repair. Squamous metaplasia most likely originates from basal cells. PMID- 11193478 TI - Phlegmonous colitis: a specific and severe complication of chronic hepatic disease. AB - Phlegmonous colitis (PC) is an acute infectious entity caused by bacteria. In this study, we reviewed 8,822 autopsy cases and found 13 cases of PC (0.15%). PC affected 2.43% of patients with hepatic cirrhosis or subacute liver atrophy, both of which were considered to be due to hepatitis viral infection. Before autopsy, none of the cases studied was suspected to involve PC, irrespective of the immediate cause of patient death. Thirteen autopsy cases showed some or all of the following pathohistologic characteristics: (1) involvement of the cecum (9 cases, 76.9%), (2) phlegmonous inflammatory changes and edema in the submucosa (100%), (3) bacterial infection (100%), (4) no microscopically detectable mucosal injuries (12 cases, 92.3%), and (5) acute serositis (peritonitis) (2 cases, 15.4%). These results suggest that PC is an unrecognized, but fatal complication of patients with some hepatic diseases and that PC has pathohistologic characteristics in common with previously reported spontaneous bacterial peritonitis in animal models. PC probably arises due to spontaneous infection in patients with hepatic cirrhosis. PMID- 11193479 TI - Inducible nitric oxide synthase expression in human urinary bladder cancer. AB - Nitric oxide (NO) is generated by a family of enzymes, nitric oxide synthases (NOS), in a wide range of mammalian cells. NO produced by the inducible NOS isoform (iNOS) has been suggested to play an important role in tumor biology with both tumor promoter and anti-tumor activity. Here, the cellular localization of iNOS in tissue of 100 cases of urinary bladder cancer was assessed immunohistologically using a commercially available antiserum. Positive iNOS immunostaining was detected in all samples of tumor tissue, whereas nonmalignant tissue adjacent to malignant areas did not show any iNOS positivity. The tumor tissue revealed a highly inhomogeneous staining pattern. In addition to uniformly stained tumor specimens, we also found markedly iNOS-positive tumor islets in the midst of unstained tumor tissue and scattered individual tumor cells expressing marked staining. In some cases, the tumor tissue showed no or only weak staining intensity. In some instances, the superficial epithelial layer of papillary carcinomas was extremely immunoreactive, in other cases it was not. Thus we were unable to show a clear correlation to tumor grade or stage. Further studies with a diversity of tumor markers including molecular genetics techniques will be necessary to elucidate how and to what extent NO and bladder cancer of different grades and stages are functionally interrelated. PMID- 11193480 TI - Influence of the chronic nitric oxide synthesis inhibition on cardiomyocytes number. AB - This work analyzes the relationship between the number of viable cells and alteration of the cardiomyocytes growth response capacity of the hypertensive rat myocardium. Hypertension was induced in Wistar rats by means of nitric oxide synthesis blockade using NG-nitro-L-arginine methyl ester (L-NAME). L-NAME (12 mg/kg per day) was given to animals in drinking water ad lib for 15 weeks. Proliferating cell nuclear antigen (PCNA) protein expression and the disector method were used to evaluate the proliferation capacity of the cardiomyocytes and its numerical density alteration (Nv[m]), respectively. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and monoclonal antibody to single-stranded DNA were two methods that detected the process of the apoptotic cell death. The association of the p53 expression with the apoptosis was investigated using anti-p53 antibody. The heart weight, body weight, and heart weight/body weight ratio of the control rats increased 114%, 77%, and 22%, respectively, and the Nv[m] decreased 60% (P<0.0001) relative to the L-NAME rats. The cardiomyocytes did not present PCNA labeling, indicating the absence of cellular proliferation. The decline of the Nv[m] was also associated with apoptotic cell death in the myocardium of the hypertensive rats. A p53-dependent pathway seems to mediate the programmed cell death in this model of hypertension. PMID- 11193481 TI - Primary neuroendocrine carcinoma with ganglion cell differentiation in a crural lymph node. AB - A primary neuroendocrine carcinoma with ganglion cell differentiation is described in a crural lymph node. The patient, a 48-year-old woman, presented a palpable lymph node of the crural region in March 1994. Histologically, the lesion was composed mostly of small cells immunoreactive for cytokeratins, neuron specific enolase and synaptophysin. The small cells merged gradually with areas containing ganglion cells immersed in a fibrillar matrix resembling neuropil. Ganglion cells expressed neuron-specific enolase, synaptophysin, neurofilament proteins and S-100 protein. Moreover, a minority of them featured cytokeratin expression. Electron microscopy was performed in the small cell component. These cells featured attenuated desmosomes and electron dense granules with an average size of 120 nm within bundles of intermediate filaments. Clinically, no tumour was found elsewhere despite extensive work-up over the 76-month follow-up period. Although similarities with previous cases of primary neuroendocrine carcinoma of lymph node, ganglion cell differentiation has never been described. PMID- 11193482 TI - Absence of a PDX-1 mutation and normal gastroduodenal immunohistology in a child with pancreatic agenesis. AB - Pancreatic agenesis is a rare condition, of which only a limited number of cases have been described. One recent paper reported a homozygous mutation in the pancreatic duodenal homeobox gene 1 (PDX-1) in a child with pancreatic agenesis. We report a 6-year-old boy with pancreatic agenesis, treated medically, without abnormalities in the PDX-1 gene coding sequence and with normal gastroduodenal endocrine cell distribution. Genes other than PDX-1 also appear to be involved in human pancreatic agenesis. PMID- 11193483 TI - CT scanning in lung cancer. PMID- 11193484 TI - "Opportunist" mycobacterial infection. PMID- 11193485 TI - Tuberculosis in Cuba. PMID- 11193486 TI - Birth weight and adult lung function in China. PMID- 11193487 TI - Hyperventilation syndrome. PMID- 11193488 TI - Supplemental oxygen in COPD. PMID- 11193489 TI - [Immunological aspects in H. pylori-associated chronic gastritis]. PMID- 11193490 TI - [Host factors in Helicobacter pylori infection]. PMID- 11193491 TI - [Cyclooxygenase activity in chronic gastritis]. PMID- 11193492 TI - [The significance of magnetic resonance cholangiopancreatography in acute cholecystitis]. AB - To clarify the significance of magnetic renonance cholangiopancreatography (MRCP) in the acute phase of acute cholecystitis, MRCP was carried out in forty-five patients with acute cholecystitis in their acute phase. The MR pericholecystic high signal was observed in 38 of the 45 patients (84%). Enlargement of the gallbladder, presence of gallstones, and impacted stones was seen in 71%, 53%, and 18%, respectively. The MR pericholecystic high signal was classified into four categories: type 0, not observed; type 1, a liner high signal; type 2, a band-like high signal; type 3, a radiating high signal. In patients who showed a type 3 MR pericholecystic high signal, 91% required percutaneous transhepatic gallbladder drainage, and most of the gallbladders were diagnosed as necrotic cholecystitis by histology. The accuracy of MRCP for the diagnosis of choledocholithiasis was 96%. It was suggested that MRCP for patients with acute cholecystitis in the acute phase provides useful information for planning the treatment. PMID- 11193493 TI - [An alpha-fetoprotein and PIVKA-II producing carcinoma of the colon: report of a case]. PMID- 11193494 TI - [A case of intractable intrahepatic cholestasis treated with coenzyme Q10 (ubidecarenone)]. PMID- 11193495 TI - [A case of hepatocellular carcinoma fed by the cystic artery treated with chemolipiodolization therapy]. PMID- 11193496 TI - [A case of hepatic biloma after less invasive therapy for HCC]. PMID- 11193497 TI - [A case of IIa + IIb-like advanced gallbladder cancer: usefulness of endoscopic double contrast cholecystography]. PMID- 11193498 TI - [A case of primary sclerosing cholangitis having autoimmune hepatitis-resembling clinical features at the onset of illness]. PMID- 11193499 TI - Dexa-measured bone density changes over time after intertrochanteric hip fractures. AB - The local bone density after an intertrochanteric hip fracture changes over time. In this study, bone density was measured in proximal femur and third lumbar vertebrae in patients treated for an intertrochanteric hip fracture at various periods. There were 60 patients (mean age 71.4 years) and 50 control patients (mean age 62.4 years). Bone density measurements were performed with Dual energy X-ray absorptiometry (DEXA). Bilateral measurements of the greater trochanter, lesser trochanter and femoral diaphysis as well as the third lumbar vertebrae were performed. Each area showed different course of change. The bone density of the greater trochanter and the lesser trochanter in the injured side increased after three months as compared with the control. After three years, the bone density of the greater trochanter decreased. The bone density of the femoral diaphysis and the third vertebrae gradually decreased over time. The authors suggest that bone density changes under the influence of callus formation, bone remodeling, decrease in daily activity, and use of ambulatory aids, etc. PMID- 11193501 TI - Chondromyxoid fibroma of the finger. AB - We report a case of chondromyxoid fibroma arising from the middle phalanx of the index finger. The radiographic and pathologic findings are described. PMID- 11193500 TI - The role of cyclooxygenase-2 and inflammatory cytokines in pain induction of herniated lumbar intervertebral disc. AB - Lumbar disc herniation (LDH) is the disease which is the major cause of radiculopathy. In terms of the pathogenesis of disease, it is reported that prostaglandinE2 (PGE2) plays an important role to induce radiculopathy. Arachidonate cascade, which is the process of PGE2 synthesis, is mainly regulated by two kinds of enzymes, phospholipaseA2 (PLA2) and cyclooxy genase (COX). Previously, PLA2 was recognized as the rate-limiting enzyme of this cascade, and some authors reported the clinical significance of PLA2 at the site of LDH concerning the radicular pain. Recently, COX was elucidated to consist of 2 types of isoform, a constitutive form of COX-1 and an inducible form of COX-2. COX-2 has been focused as a key enzyme to regulate PGE2 synthesis and plays an important role in inflammation, because COX-2 was induced in many types of cells by the stimulation of inflammatory cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha). However, it is not fully discussed whether or not, COX-2 is induced in lumbar disc tissue and if it plays a significant role in the pathogenesis of LDH. To clarify the role of COX-2 in the pathomechanism of radiculopathy of LDH, we have investigated the expression of COX-2, IL-1 beta and TNF alpha in herniated lumbar disc tissue. Immunohistologically, they were detected in the cytosol of chondrocytes constituting the disc tissue. RT-PCR showed that herniated lumbar disc-derived cells expressed mRNA of COX-2, IL-1 beta and TNF alpha in the presence of inflammatory cytokines in vitro. The disc-derived cells also produced much PGE2 by stimulating of inflammatory cytokines at the same time and this PGE2 production was distinctly suppressed by a selective inhibitor of COX-2, 6-methoxy 2-naphtyl acetic acids (6MNA). These results suggest that COX-2 and inflammatory cytokines might play a causative role in the radiculopathy of LDH through upregulating PGE2 synthesis. PMID- 11193502 TI - A case of adenoma of the ampulla of Vater. AB - A case of adenoma of the ampulla of Vater is presented in a 48-year-old man who was admitted with epigastric pain. Gastroendoscopy revealed a sessile tumor about 3 cm in diameter at the ampulla of Vater, and the pathological diagnosis of a biopsy specimen was adenoma with moderate atypia. Because of the possibility of a malignant component, pylorus-preserving pancreatoduodenectomy was performed to avoid local recurrence. The final pathological diagnosis was adenoma with severe atypia. PMID- 11193503 TI - The results of anterior radical debridement and anterior instrumentation in Pott's disease and comparison with other surgical techniques. AB - Classic procedure in the treatment of vertebral tuberculosis is drainage of the abscess, curettage of the devitalized vertebra and application of antituberculous chemotherapy regimen. Posterior instrumentation results are encouraging in the prevention or treatment of late kyphosis; however, a second stage operation is needed. Recently, posterolateral or transpedicular drainage without anterior drainage or posterior instrumentation following anterior drainage in the same session is preferred to avoid kyphotic deformity. Seventy-six patients with spinal tuberculosis were operated in the 1st Department of Orthopaedics and Traumatology, Ankara Social Security Hospital, between January 1987 and January 1997. There were four children in our series. Average follow-up period was 36.1 +/- 14.5 months and the average age at the time of operation was 40.8 +/- 15.2 years. This study reports the surgical results of 45 patients with Pott's disease who had anterior radical debridement with anterior fusion and anterior instrumentation [14 patients with Z-plate and 31 patients with Cotrel-Dubousset Hopf (CDH system)]. The results are compared with those of 8 patients who had posterolateral drainage and posterior fusion, 12 patients who had only anterior drainage and anterior strut grafting and, 11 patients who had posterior instrumentation following anterior radical debridement in the same session in terms of fusion rates, correction of kyphotic deformity, recurrence rate and clinical results. All patients had one year consecutive triple drug therapy. Preoperative 23.2 degrees +/- 12.5 degrees local kyphosis angle was lowered to 6.1 degrees +/- 6.9 degrees with a correction rate of 77.4 +/- 22.3%. When the other three groups which had been instrumented were compared, the correction rates in the local kyphosis angle values were not statistically different and the variation in loss of correction at the last follow-up was also statistically insignificant. The sagittal contour of the involved vertebra's region did not change in the uninstrumented group, while it did so in instrumented groups which had normal range values postoperatively. Overall, 27 patients had neurologic deficits preoperatively. Twenty of these (74.1%) had complete, and 5 (18.5%) had partial recovery with a combined 92.6% neurologic improvement. All the patients had a solid fusion mass at the last controls. Reactivation was not seen. Additionally, contrary to the common belief, anterior instrumentation which anterior autologous strut grafting following anterior radical debridement can be a good treatment option with low complication rate, high correction rate in acute local kyphosis, and high fusion rate. PMID- 11193504 TI - Diagnostic value of MRI for the female urethral diverticulum. AB - A woman, who discharged pus at the time of intercourse, was diagnosed to have a urethral diverticulum by combination of urethroscope and MRI. MRI provided clear view of the diverticulum in terms of the relationship with the surrounding organs. PMID- 11193505 TI - A study on the development and the deodorizing capability of metal-phthalocyanine processed stump socks for amputees. AB - The socks which were treated with Metal-Phthalocyanine, a derivative of an artificial enzyme, were developed by the author and called Kobe Stump Socks(KSS). KSS was made of a cotton cloth that had undergone an ammonium salt cationization process and also a Metal-Phthalocyanine process. The study from a bacteriological view and the moisture absorption effect of KSS revealed that the mechanism of the deodorizing ability was bared on the decomposition function of Metal Phthalocyanine, while the antibacterial function came from the cationization and also that the high water absorption speed and capacity further enhanced these two functions. In this report, the author studied the deodorizing capability of KSS. To measure the adherence of an odor substance, ammonia, a testing device that measured this adherence was used. As a result, the adherence of ammonia to KSS was more than three times that of an unprocessed cloth. KSS had been used as stump socks on the stumps of amputees who were using prosthetic limbs, and a snuff test on the difference of the odor strength inside the socket was done. Of 33 subjects, 32 recognized a deodorizing effect. From these facts, KSS was proven to dry and deodorize the limb surface with the moisture absorption effect and deodorizing capabilities due to the Metal-Phthalocyanine process. These characteristics were never recognized in other stump socks. These date mentioned above suggested that KSS was the best material to deodorize prosthetic limb sockets. PMID- 11193506 TI - Early lesions of cerebral atherosclerosis from induced hypertension in Watanabe heritable hyperlipidemic rabbits. AB - Watanabe heritable hyperlipidemic (WHHL) rabbits are well known to develop severe atherosclerotic lesions in extracranial arteries but not in cerebral arteries. In the present work we produced and investigated atherosclerotic lesions in cerebral arteries of WHHL rabbits by inducing hypertension. Hypertension was induced by right nephrectomy and surgically induced stenosis of the left renal artery. Six months after surgery the rabbits were killed for morphologic, immunohistochemical and transmission electron microscopic studies of extracranial and cerebral atherosclerosis. A significant rise in systolic blood pressure was evident 3 months after surgery in the hypertensive group (p < .001). Atherosclerotic lesions had developed areas near the vertebral-basilar arterial confluence and the circle of Willis in the hypertensive Watanabe rabbits by 6 months after surgery (p < .001). Atherosclerotic lesions in cerebral arteries remained less severe than in the aorta and coronary arteries, and showed qualitative morphologic differences. This is the first report of production by hypertension of experimental cerebral atherosclerosis in the WHHL rabbits, indicating that hypertension as well as hyperlipidemia was required for development of lesions in cerebral arteries. This model should be useful for studying development of cerebral atherosclerosis and may contribute to improved prevention and treatment of the human disease. PMID- 11193507 TI - [The effect of sevoflurane and enflurane on renal sympathetic nerve activity in sinoaortic denerved rabbits]. AB - We assessed the effects of sevoflurane and enflurane, i.e. halogenated volatile anesthetics, on blood pressure, heart rate, and renal sympathetic nerve activity (RSNA) in rabbits. To eliminate the influence of baroreceptor reflex, bilateral carotid sinus nerve branches and vagus nerves were resected before the measurements. Sevoflurane and enflurane [0.5-1.15 MAC (minimum alveolar anesthetic concentration)] did not significantly change heart rate, but decreased mean blood pressure in a concentration-dependent manner. On the other hand, while sevoflurane did not significantly attenuate RSNA, enflurane decreased it in a concentration-dependent manner. There was a significant difference between sevoflurane and enflurane in their effects on RSNA. These results suggest that a decrease in blood pressure caused by sevoflurane is related to factors other than sympathetic nerve activity, and that hypotension caused by enflurane is related more closely to attenuated activity of sympathetic nerve, at least, in comparison with sevoflurane. PMID- 11193508 TI - [Effects of intravenous nicardipine, prostaglandin E1, nitroglycerin, sodium nitroprusside, and epidural lidocaine on hepatic and renal blood flow during hypotensive anesthesia]. AB - We studied the effects of intravenous nicardipine (NIC), prostaglandin E1 (PGE1), nitroglycerin (TNG), sodium nitroprusside (SNP) and epidural lidocaine (LID) on hepatic and renal blood flow during general anesthesia (nitrous oxide-oxygen sevoflurane) in 46 female patients undergoing unilateral total hip arthroplasty. During operations, hepatic blood flow, glomerular filtration rate, renal plasma flow, and renal tubular injury were measured by R 15 ICG (15 minutes retention rate of indocyanine green), CCR (creatinine clearance), CPAH (para-aminohippuric acid clearance), and urinary excretion of NAG and beta 2-microglobulin. Significant elevation of R 15 ICG was observed in the hypotensive state in the TNG group and the elevation of R 15 ICG indicates that blood flow to the liver has decreased during hypotensive anesthesia. Urine volume in the PGE1 group was larger than that in the TNG, SNP or LID group. CCR in the PGE1 group was larger than that in the NIC, TNG or SNP groups. CPAH in the PGE1 group was larger than that in the SNP or LID group. The value of urine NAG in the TNG group was larger than that in the NIC or PGE1 group. The value of urine beta 2-microglobulin in the NIC group was larger than that in the PGE1 or SNP group. The results of urine volume, CCR, CPAH, urine NAG, and urine beta 2-microglobulin indicate that blood flow to the kidneys was greater in the PGE1 group as compared to other groups. This study indicates that prostaglandin E1 is the best hypotensive drug for hepatic and renal blood flow during hypotensive anesthesia. PMID- 11193509 TI - [Hemodynamic and pulmonary effects of fluid resuscitation from hemorrhagic shock in the presense of mild pulmonary edema]. AB - The hemodynamic and pulmonary effects of fluid resuscitation with crystalloid and colloid solutions in the presence of mild pulmonary edema were investigated. Anesthetized dogs received oleic acid to increase pulmonary capillary permeability, and one hour later bled to produce hemorrhagic shock. One hour after the shock, resuscitation was performed with Ringer's lactate, 6% hydroxyethyl starch (HES) solution, or dog's plasma. Resuscitation from hemorrhagic shock restored hemodynamics to pre-hemorrhagic levels with all of the above solutions. Ringer's lactate resuscitation resulted in increases in extravascular lung water volume (EVLWV) and oxygen consumption, and decreases in colloid osmotic pressure and oxygen delivery. Resuscitation with HES solution and plasma did not result in increases in EVLWV, but with HES solution resulted in decreases in colloid osmotic pressure to pre-hemorrhagic levels in two hours. This suggests that the resuscitation with HES solution can not maintain colloid osmotic pressure for more than two hours. The author concludes that the hemodynamic and pulmonary effects of HES solution and plasma are similar in mild lung injury cases. PMID- 11193510 TI - [Adrenergic receptor and knockout mouse: 1) Beta adrenergic receptor knockout mouse]. AB - Functional analysis of beta 1 and beta 2 adrenergic receptor (AR) subtypes has been made possible by establishing knockout mice (KO) with abolished beta 1 and/or beta 2 AR expression. Neither resting heart rate nor resting blood pressure of beta 1 AR KO, beta 2 AR KO, or beta 1/beta 2 KO differed significantly from those of wild-type mice. The chronotropic response to isoproterenol was significantly attenuated in beta 1 AR KO and beta 1/beta 2 KO, whereas there was no detrimental effect on heart rate in beta 2 AR KO. This suggests that chronotropy is mediated by beta 1 AR. In terms of the vasodilatory response to isoproterenol, there appears to be a graded and additive attenuation of the hypotensive response in beta 1 AR KO, beta 2 AR KO, and beta 1/beta 2 KO. Vascular relaxation is thought to be controlled by both beta 1 AR and beta 2 AR. Tachycardia induced by exercise was significantly attenuated in beta 1 AR KO, and beta 1/beta 2 KO. beta 2 AR KO subjected to treadmill exercise showed significant hypertension, increased oxygen consumption, and ability of long distance running. PMID- 11193511 TI - [One-stage surgery of minimally invasive direct coronary artery bypass, abdominal aortic aneurysm repair and carotid endarterectomy]. AB - A 74 year-old man with bladder transitional carcinoma had severe multivascular disease; coronary artery stenosis, abdominal aortic aneurysm and right internal carotid artery stenosis. First, transurethral bladder tumor resection (TUR-Bt) was performed twice but in the second TUR-Bt, no carcinoma cell was found. One stage surgery of minimally invasive direct coronary artery bypass (MIDCAB), abdominal aortic aneurysm (AAA) repair and carotid endarterectomy (CEA) was proposed. MIDCAB was performed first. Inspite of the bradycardia, heart oppression by stabilizer and coronary artery clamping, blood pressure and ST segments were stable. With heparinization and the chest left open, AAA repair was carried out. On aorta clamping and declamping, blood pressure and heart rate were stable. After completion of AAA repair, heparinization was reversed with protamine. Chest and abdominal wounds were closed simultaneously. CEA was performed lastly, because the patient had no cerebral ischemic symptom and no risk of cardiopulmonary bypass. After the operation, no neurologic deficit appeared. This experience of one stage surgery was reported with review of literatures. One stage surgery is a possible approach to the patients with severe multivascular disease. PMID- 11193512 TI - [Influence of injection speed of the spread of 4.0 ml of 0.5% isobaric bupivacaine in spinal anesthesia]. AB - Influence of injection speed on the spread of isobaric 0.5% bupivacaine 4.0 ml was studied in 100 patients to analyze the correlation between analgesia levels and patient's characteristics. All patients (ASA PS I.II) were scheduled for orthopedic or urological procedures, and received no premedication. They were randomly divided into two groups by injection speed; group 1 of 0.2 ml.sec-1 and group 2 of 0.03 ml.sec-1. Spinal tap was performed in lateral decubitus position at the L 3-4 intenspace with median approach, using a 25 G Quincke needle. Immediately after the injection, the patient was placed in supine position. The maximum sensory block was tested by pinprick method, and no significant difference in the height of sensory block was observed between the two groups. No significant correlation with patient's characteristics was observed except body weight in group 1. This study suggests that the speed of injection does not influence the spread of isobaric 0.5% bupivacaine 4.0 ml. PMID- 11193513 TI - [A modified technique for insertion of the laryngeal mask airway in children]. AB - We modified the technique for laryngeal mask airway (LMA) insertion in children. This modification involves inserting a two-thirds inflated LMA with its lumen facing laterally toward left and then rotating it 90 degrees clockwise as it passes downwards into position behind the larynx. Then the cuff is inflated fully. We conducted a survey on the use of LMA in ten consecutive children for minor superficial surgery. After slow induction, anesthesia was maintained with 3.0% of end-tidal sevoflurane concentration in 100% oxygen for 5 minutes before insertion of LMA. No muscle relaxant was used. Successful insertion was judged by the clinical integrity of the airway. The standard LMA insertion technique or another airway device was applied when three trials had failed. Traumatic insertion was observed by the attachment of blood clots to the surface of the removed LMA. A satisfactory airway was achieved in all of the children who participated in the survey. There were no significant differences in vital signs between pre- and post-insertion. Only one child was found to have attachment of blood clots on the surface of the removed LMA. We conclude that our technique would be one recommended method in pediatric practice. PMID- 11193514 TI - [Anesthetic management of two patients with polymyositis]. AB - We report anesthetic experience of two patients suffering from polymyositis. The first case is a 56 year old woman who underwent tympanoplasty for cholesteatoma of the middle ear. Anesthesia was induced with thiopental and deepened with oxygen-nitrous oxide and sevoflurane. No muscle relaxant was used for endotracheal intubation and for maintaining anesthesia. Another is a 61 year old man who underwent open reduction and internal fixation for condyle fracture of the tibia. Epidural catheter was inserted at L 3-L 4. Epidural blockade was established with 2% mepivacaine, and sedation was achieved by intravenous midazolam. Concerning the anesthetic management of a patient with polymyositis, there are some informations on the appropriate use of muscle relaxants. It is generally believed that the patient is sensitive to nondepolarizing muscle relaxants and the use of antagonist drug (reversal) may cause muscle weakness, severe dysrhythmia, et al. Therefore we think it is appropriate to manage such a patient without muscle relaxants. PMID- 11193515 TI - [A case of fixed drug eruption due to ephedrine hydrochloride]. AB - We report the case of a 29-year old female who developed a fixed drug eruption due to ephedrine hydrochloride administered intravenously during the cesarean section. On the day of the operation a palm-sized dark brown macula with half egg sized erosion appeared on her right lower thigh. We diagnosed her disease as fixed drug eruption and examined the causative agent among all the 14 drugs used from admission to the appearance of fixed drug eruption. Each of systemic challenge, patch test on the lesion, intradermal and subcutaneous injection on the lesion with ephedrine hydrochloride showed positive reaction. As far as we have been able to search, our case is the first one of fixed drug eruption due to ephedrine hydrochloride. PMID- 11193516 TI - [Localized right atrial tamponade after aortic valve replacement]. AB - A 78-year-old man developed isolated right atrial tamponade 15 hours following aortic valve replacement. There were excessive postsurgical bleeding, low blood pressure, and low cardiac output. Volume expansion and inotropic therapy did not increase blood pressure. There were no cardiomegaly and echo-free space. Diagnosis was made by appearance of pulsus paradoxus and transthoracic echocardiography and confirmed by surgery. The clinical picture was improved dramatically after surgical removal of the hematoma. Right atrial tamponade leads to a unique clinical conglomeration of hemodynamic and echocardiographic features. Constant attention to this entity is necessary to make a timely diagnosis. PMID- 11193517 TI - [Anesthetic management of MIDCAB in a patient with Wolff-Parkinson-White syndrome]. AB - We experienced the anesthetic management of a minimally invasive direct coronary artery bypass (MIDCAB) in a patient with Wolff-Parkinson-White (WPW) syndrome. A 55-year-old male had chest pain on effort and was diagnosed as having stenosis of the left coronary artery (#6). He was scheduled to undergo MIDCAB. Anesthesia was induced with midazolam 5 mg, fentanyl 300 micrograms, and vecuronium 10 mg and maintained with air-oxygen, propofol, and fentanyl (27 micrograms.kg-1). Diltiazem was continuously infused at a rate of 0.5-1.5 micrograms.kg-1.min-1 throughout the surgery. The hemodynamic parameters were maintained stable and paroxysmal supraventricular tachycardia was not observed during the procedure. We conclude that the administration of propofol and a medium dose of fentanyl is useful for the anesthetic management of MIDCAB in patients with WPW syndrome and that intraoperative administration of diltiazem might be needed to avoid paroxysmal supraventricular tachycardia. PMID- 11193518 TI - [Anesthetic management of a patient with hepatocellular carcinoma with tumor thrombus extending into the right atrium]. AB - A 58 year-old male was scheduled for surgery of his hepatic cancer. Tumor invaded to the right atrium through the inferior vena cava. The operative method of removing the tumor in the right atrium was scheduled under extracorporeal circulation after the left lobe hepatectomy. Since there was a tumor in the right atrium, central venous pressure monitoring could not be reliable. Transesophageal echocardiography (TEE) was employed in order to detect the part of the tumor flowing into the pulmonary artery or occluding the tricuspid valve. Due to massive blood loss during hepatectomy, the capacity in the right atrium decreased and the tumor was often about to engage the tricuspid valve. After the rapid fluid therapy, the right atrium capacity increased preventing the engagement of the tumor. TEE was useful not only to observe the movement of the tumor in the right atrium but also to monitor the circulating blood volume. PMID- 11193519 TI - [Problems in clinical use of intraarterial blood gas monitoring system, Paratrend 7]. AB - We evaluated the intraarterial blood gas monitoring system Paratrend 7 in clinical use. One hundred and sixty six sensors used for patients receiving thoracic, open heart or great vessel surgery were tested for one year, prospectively. Sensors were inserted through a 20 G intraarterial cannula into the radial artery before operation and removed when they malfunctioned or seemed to be not necessary for patient management in critical care unit. We encountered several problems such as, initial calibration failure (5/166), impossible sensor insertion (2/166), arterial pressure wave change (5/166), parameter display failure (21/166), and thrombus in the circuit (9/166). Parameter display failure after insertion tended to occur on patient's arm movement imparing the sensor. No serious accident, such as arterial thrombosis was experienced. Some troubles were due to staff's incorrect handling of the apparatus. Training of staffs is indispensable for safe and sufficient utilization of Paratrend 7. PMID- 11193520 TI - [Analysis of inadvertent epidural injection of drugs]. AB - We asked 31 anesthesiologists, who were on the Japanese Board of Anesthesiology, about inadvertent injection of drugs into the epidural space, and received answers from 28 (90%). Fifteen (54%) had an experience of inadvertent epidural injection, and five of them had two experiences. Injected drugs were ephedrine (6 times), a mixture of neostigmine and atropine (3), thiopental (2), etilefrine (2), vecuronium (1), suxamethonium (1), bicarbonate (1), midazolam (1), lactated Ringer's solution (1), nicardipine (1), and pentazocine (1). The inadvertent injection of thiopental or bicarbonate was noticed by back pain during injection. No treatment was added after the inadvertent injections, except a patient with an epidural steroid injection following thiopental. No neurological complications were found in any patients. PMID- 11193521 TI - [Anesthesia in a children's hospital in Nepal]. AB - The author experienced ten cases of anesthesia in a children's hospital in Nepal. Eight cases were pediatric surgeries and two cases were gynecological procedures. Halothane or intravenous ketamine anesthesia was performed in pediatric cases. Regional block or intravenous ketamine anesthesia was performed in gynecological cases. Oxygen supply stopped during anesthesia in one case, and patient was resuscitated by ambu-bag with room air. Electricity was interrupted in one case, and operation was continued with only one battery light. There is no mechanical ventilator nor nitrous oxygen in the hospital. Air conditioning was not in the operating room although the hospital was situated in the subtropical area and room temperature reached up to 40 degrees. Electrocardiogram and suction machines were present, but they were out of order. The anesthetic technique required in the developing countries is not so simple. Especially for young doctors trained among so many sophisticated monitors, anesthesia in the developing countries is not only an experience of volunteer, but provides effective training of pediatric anesthesia for strengthening their sense and skills. PMID- 11193522 TI - [Safety of intraoperative autotransfusion using the closed-circuit autotransfusion system in Jehovahs witnesses patient]. PMID- 11193524 TI - [Tentorial meningioma: surgical anatomy and approaches]. PMID- 11193525 TI - [Postoperative evaluation of EC/IC bypass surgery--long-term follow up study by donor artery compression test]. AB - Focal cerebral vascular dependency of donor arteries was evaluated in 45 patients who had undergone EC/IC bypass surgery. During EEG recording, digital compression was applied to the anastomosed donor superficial temporal artery (STA) at the preauricular region. The appearance of slow waves on the EEG recording suggests hypofunction of the local brain. In cases showing positive response to the STA compression test, we suggest that the blood supply via STA is an essential collateral route to the ischemic brain. The test was periodically repeated in the postoperative follow-up period for a mean of seven years. Eleven cases (24%) showed positive results in the STA compression test during the long-term postoperative follow-up period. PMID- 11193526 TI - [Diagnosis of brain tumor with proton MR spectroscopy--the quantification of gliomas compared with normal brain]. AB - We conducted quantification of proton MR spectroscopy (MRS) using water signal as an internal standard, in order to quantify the concentrations of metabolites in normal adult brains and in gliomas in vivo. Single-voxel spectra were acquired using a point-resolved spectroscopic (PRESS) pulse sequence as part of the Probe. P spectroscopy package on a GE Signa Horizon Hispeed LX1.5T scanner (TR/TE/Ave = 3000 msec/30 msec/64). The volume of interest (VOI) varied from 15.0 x 15.0 x 15.0 mm3 to 20.0 x 20.0 x 20.0 mm3 for the brain. The present study included 26 healthy volunteers and 12 patients with gliomas, whose diagnoses were verified by histologic examination. The calculated concentrations of N-acetyl-aspartate (NAA), creatine (Cre) and choline (Cho) in normal hemispheric white matter were 23.66 +/- 1.94 mM (mean +/- SD), 12.97 +/- 1.44 mM, and 4.38 +/- 0.60 mM, respectively. We found they were not necessarily uniform in different parts of the brain, for example, in the pons and basal ganglia. The concentrations of NAA and Cre decreased in all gliomas (p < 0.001). Cho concentration also decreased in the glioma (p < 0.005). The NAA/Cre, NAA/Cho, and Cre/Cho ratios can distinguish normal brain from gliomas, and NAA/Cho ratio can distinguish low-grade astrocytoma from the high-grade group. The results indicate that this noninvasive method offers reasonable estimation of metabolite concentrations in the brain in vivo and therefore is useful in diagnoses of gliomas. PMID- 11193527 TI - [The efficacy and safety of the nicardipine prolonged-release implant in a canine double hemorrhage model]. AB - A drug delivery system using copoly (lactic/glycol acid) was tested to determine its efficacy and safety in preventing cerebral vasospasm following subarachnoid hemorrhage in dogs. Rod shaped implants (1 mm diameter, 10 mm length, and approximately 10% of nicardipine) was prepared by a heat compression method. Ten dogs were assigned to two groups: double hemorrhage group and double hemorrhage group treated with implants. Vertebral angiography and arterial blood injection into the cisterna magna were performed, followed by midline suboccipital craniectomy and laminectomy of the atlas and placement of nicardipine implants in the cisterna magna. On day 2, arterial blood injection into the cisterna magna was repeated (double hemorrhage model). On day 7, vertebral angiography was repeated. The animals were then sacrificed and the brain and blood clot were taken out. All the animals involved in both groups had been clinically well. Though 5 animals of the control group showed severe vasospasm, no vasospasm was observed in 3 animals and only very mild vasospasm in 2 of the nicardipine treated group. There was a statistically significant difference in diameter between the two groups (0.5 mm vs 1.1 mm, p = 0.009). Histological examination showed no specific changes related to implants. Furthermore, left frontotemporal craniotomy and placement of nicardipine implants in the carotid-optico cistern were preformed in 3 dogs. Neither clinical symptoms related to implants nor specific histological changes were observed (e.g. hypotension, seizure). These results suggested that nicardipine-prolonged release preparation is safe as well as effective for cerebral vasospasm. PMID- 11193529 TI - [Ultrasonic aspirator with controllable suction system--variable action suction adapter and clinical experience with it]. AB - While the ultrasonic aspirator (UA) has been widely used as one of the indispensable tools in the field of neurosurgery, a potential risk when using the present UA is injury to the neurovascular structures due to ultrasonic pulverization and constant forceful suction power. We have devised a small variable action suction adapter that can be used in a similar manner to conventional surgical suction tubes. The UA control unit and the handpiece used in this study were the Sonopet UST-2000 and HA-01, respectively (M & M Corporation Tokyo, Japan). The handpiece is slim, with the mid-portion diameter of 13 mm, and it weighs 100 grams. A variable action suction adapter was made from polycarbonate of 15 x 12 x 13 mm in size. The adapter was connected to the suction tube using a Y-shaped connector (Fig. 2 A), which was integrated into the handpiece. The suction power is regulated by variably closing the oval-shaped hole. The adapter can be variously placed on and rotated around the handpiece (Fig. 2 B and C) so that either the right or left hand handles it in a similar fashion to conventional suction tubes. We used this UA in surgery for 8 patients with large brain tumors (meningioma in 5 cases, metastatic brain tumor in 2 cases and glioma in one case). It reduced the risk of suction-related injury to the neurovascular structures and was handled in a similar manner to conventional suction tubes. This adapter ensures the complete control of suction power, which will reduce the risk of suction injury. PMID- 11193528 TI - [Recurrence of cerebral aneurysms in the long-term follow-up after aneurysm surgery]. AB - We investigated late aneurysmal recurrence in 71 patients who underwent direct operations for intracranial aneurysms during the period from 1981 to 1988 and were under 50 years old at the time of operation with ADL rating of 1 or 2 at discharge. And out of the 71 patients, four had already sustained reattack of SAH and been confirmed to have recurrent anuerysms. Another two had been diagnosed as harboring unruptured recurrent aneurysms. Cerebral angiography was carried out for nine patients in the remaining 63, revealing aneurysmal recurrence in four patients. Overall, 14 recurrent aneurysms, 11 de novo and 3 regrowth aneurysms, have been found in 10 patients. Considering the high risk of aneurysmal recurrence, postoperative long-term follow-up including MRA and angiography is mandatory, especially for relatively young patients. PMID- 11193530 TI - [Surgical treatments for 7 pituitary adenomas in multiple endocrine neoplasia type 1]. AB - We analyzed 7 pituitary adenomas in patients with multiple endocrine neoplasia type 1 (MEN1). Their incidence was 1.6% among 450 patients with pituitary adenomas which had been treated surgically in our department between 1978 and 1999. The age, gender, symptoms, type of hormone secretion, pathological and operative findings in the MEN1 patients were not apparently different from those in the non-MEN1 patients. Incidence of non-functioning pituitary adenomas, however, was more frequently encountered in our series than that in previous reports among Caucasian people. One patient who had 5 previous operations for the MEN tumors died following postoperative subarachnoid hemorrhage. Four of the seven patients presented initial symptoms related to pituitary adenomas and increased serum Ca level was retrospectively recognized in three of the four at the time of treatment for the pituitary adenomas. PMID- 11193531 TI - [Production and clinical application of fibrin sealant with high concentrated fibrin (fibrin patch)]. AB - OBJECT: The sealing properties of fibrin sealant with high concentrated fibrin (fibrin patch) were examined. MATERIAL AND METHODS: A commercial fibrin sealant (Bolheal) produced from pooled human plasma was utilized for this study. The fibrin sealant made of fibrinogen and thrombin solutions mixed in a volume ratio 5:1 was applied as the fibrin sealant with high concentrated fibrin (fibrin patch). The burst pressure of the fibrin clots of either 1:1 or 5:1 mixing ratio, which sealed the small holes, was measured by a water-leak preventing model. The tensile strength of the fibrin patch was measured by the breaking pressure of the fibrin clot. The burst pressure of the fibrin patch, which sealed the dural defect with a diameter of 15 mm, was compared with that of expanded polytetrafluoroethylene (ePTFE). RESULTS: The burst pressure was elevated from 287 +/- 23.1 to 445 +/- 30.5 mmHg by changing the mixing ratio from 1:1 to 5:1. The breaking pressure of the fibrin patch showed 131 +/- 25.4 mmHg and that of the patch mixed at the ratio of 1:1 showed 46.6 +/- 9.9 mmHg. The result of dural repair with the fibrin patch revealed higher sealing effectiveness than that of ePTFE. The burst pressure averaged 70.5 +/- 21.4 mmHg in the fibrin patch samples and 51.4 +/- 13 mmHg in the ePTFE samples. CONCLUSION: The fibrin patch revealed higher performance as a sealant and has the potential to be a candidate for acceptance as the new dural repair material. PMID- 11193532 TI - [Improvement of visual function after balloon angioplasty for innominate artery stenosis: a case report]. AB - Occlusive disease of the innominate artery is relatively rare, but visual disturbance is a frequently encountered manifestation of this disease. A 48-year old man presented with a 1-year history of right amaurosis fugaxs. During the nine years prior to admission, the patient had undergone aortic artery-coronal artery bypass surgery two times. Upon ophthalmological examination, the patient was found to have impaired right retinal sensitivity and prolonged right arm-to retina circulation time. Aortic arch angiography demonstrated severe stenosis of the innominate artery near its origin. The stenosis was successfully treated by balloon angioplasty. Subsequently, right retinal sensitivity improved and right arm-to-retina circulation time normalized following the procedure. These findings indicate that this patient had sufferred impaired visual function due to hemodynamic retinal ischemia caused by innominate artery stenosis. PMID- 11193533 TI - [Two cases with coil embolization following incomplete neck clipping]. AB - We report two cases with embolization (coil embolization) using Guglielumi detachable coils of residual aneurysms following incomplete neck clipping. The first case, a 75-year-old woman suffered from a subarachnoid hemorrhage due to the rupture of a left internal carotid posterior communicating aneurysm in June, 1997. Neck clipping of the aneurysm was performed at day 1. Follow-up angiogram at day 7 showed a residual aneurysm involving the dome of the initial aneurysm. We performed coil embolization of the residual aneurysm following the angiogram. Almost complete obliteration of the aneurysm lasted during the follow-up period of two and a half years. The second case, a 71-year-old woman suffered from a subarachnoid hemorrhage due to the rupture of a right internal carotid posterior communicating aneurysm in May, 1999. Neck clipping of the aneurysm was performed at day 1. Follow-up angiogram at day 7 showed a residual aneurysm involving only a part of the initial aneurysm near the neck. Because no spontaneous thrombosis of the residual aneurysm was obtained after 2 months, we performed coil embolization of the residual aneurysm. Almost complete obliteration of the aneurysm lasted during the follow-up period of 7 months. These patients were discharged with good performance status. We consider the morphologic feature of the residural aneurysm to be most important for determining when to perform coil embolization of such residual aneurysms. PMID- 11193534 TI - [Craniopharyngioma presenting a symptom of pituitary apoplexy and hyponatremia: a case report]. AB - We report a case of a 70-year-old woman admitted to our hospital with sudden headache, drowsiness and hyponatremia. MRI on admission showed an intrasellar mass with suprasellar extension. Serum examination revealed decreased sodium and hypopituitarism, but they were normalized gradually by compensation using hydrocortisone, thyroid hormone and salt. Afterwards, masked diabetes insipidus appeared and required aqueous pitressin for the control of urine volume. A removal operation was performed uneventfully using the transsphenoidal approach and histological examination confirmed squamous-papillary type craniopharyngioma. Intratumoral hemorrhage of the craniopharyngioma is extremely rare. These cases tend to occur after over 15 years of maturation and the squamous-papillary type tend to bleed more than the adamantinomatous type. However, it is very difficult to make a differential diagnosis between craniopharyngioma with intratumoral hemorrhage and pituitary apoplexy, judging only by symptoms or interventional radiology. The definite mechanism of hyponatremia associated with a parasellar lesion is still obscure, but compression to the anterior hypothalamus or pituitary gland by an enlargement of the parasellar tumor is generally hypothesized. PMID- 11193535 TI - [A case of metastatic tumor of the pituitary gland presenting as a subarachnoid hemorrhage]. AB - We reported the case of a 55-year-old man with metastatic tumor of the pituitary gland who suffered from symptomatic pituitary apoplexy with subarachnoid hemorrhage. The patient, who had sigmoid colon carcinoma and left parietal metastatic brain tumor, developed severe headache and decrease of right visual acuity. CT showed a pituitary mass with subarachnoid hemorrhage. Transsphenoidal surgery was performed after replacement therapy with corticosteroids. Histological examination revealed metastasis of adenocarcinoma. Pituitary apoplexy is an unusual manifestation of metastatic pituitary tumor. The case of metastatic tumor of the pituitary gland presenting as subarachnoid hemorrhage such as this case is especial rare. PMID- 11193536 TI - [Multiple sclerosis]. PMID- 11193537 TI - [Therapy of paraneoplastic neurological syndrome]. PMID- 11193538 TI - [Treatment of chronic inflammatory demyelinating polyradiculoneuropathy(CIDP)--a review]. AB - This is a review article about the recent progress and the general consensus of the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Although the first line treatment is believed to be adrenocorticosteroid prescribed orally or intravenously, some insist that plasmapheresis or intravenous immunoglobulin is better. The latter two are expensive but the effects are comparable to that of steroid, and in some patients complete remission might be induced. On the other hand, about 30% of patients do not respond to any of these conventional procedures, and for these the combination of two or three of them might be effective. As another choice, immunosuppressant or interferon (alfa-2 a or beta-1 a) has been applied although its usefulness is still inconclusive. For any of these here mentioned, the clinical response greatly varies among patients, and the elucidation of predictive factors of effectiveness is eagerly awaited from the standpoint of reasonable treatment selection and cost-effectiveness. PMID- 11193539 TI - [Human immunodeficiency virus-associated dementia: review of pathogenesis and treatment studies]. PMID- 11193541 TI - [Staged total callosotomy for medically intractable seizures]. AB - For the treatment of intractable generalized epilepsies, two-staged total callosotomy was performed in five patients. In all patients, preceded anterior callosotomy failed to obtain satisfactory seizure control. All patients showed mental retardation with various degrees. Mean age at the first operation was 10.2 years and 4 patients were operated in their childhood. All patients showed various types of seizures; drop attack (DA) in 3 patients, tonic seizure (TS) in 2, myoclonus (MY) in 2, complex partial seizure (CPS) in 2, atypical absence (AA) in 1, and head drop (HD) in 2. After anterior callosotomy, complete cessation of CPS and 50-80% reduction of DA was obtained in one, respectively. However, only less than 50% reduction of seizures was obtained in other types of seizures. Two years after anterior callosotomy, posterior portion of the corpus callosum was divided. After staged total callosotomy, complete cessation of DA was obtained in all patients and 80-100% reduction of AA was obtained in one patient. One adult patient showed the disconnection syndrome which did not affect activities of his daily life. Our study revealed the efficacy of posterior callosotomy in DA patients with unsatisfactory results after anterior callosotomy. This strategy should be considered especially in childhood cases, since obvious complication was not observed in such cases. PMID- 11193540 TI - [Comparison of nerve conduction studies between conventional and lumbrical/interossei recording methods in diabetics]. AB - Median nerve conduction studies were performed by conventional and lumbrical/interossei recording methods. The former is composed of recordings of compound muscle action potential from abductor pollicis brevis (APB) and sensory nerve action potential from second digit (D) after wrist stimulation. In the latter the recording electrode was placed lateral to the midpoint of the 3rd metacarpal bone, and recorded compound muscle action potential from the 2nd lumbrical (2 L) and sensory nerve action potential from the digital nerve (N) after wrist stimulation. Subjects were 57 healthy individuals and 97 patients with diabetes mellitus. Particularly in diabetic patients values of coefficient of correlation between each measurement were high enough; i.e., r = 0.91 between latencies to 2 L and APB, r = 0.55 between amplitudes of 2 L and APB, r = 0.86 between amplitudes of N and D. Corresponding measurements by conventional method and lumbrical/interossei method were identical in the values of coefficient of correlation between measurements. The characteristics of lumbrical/interossei method are to be able to record compound muscle action potentials and nerve action potential from the same electrode. In this study values obtained by lumbrical/interossei method showed identical correlation between measurements to the corresponding ones by conventional method. In conclusion recordings of APB and D by conventional method can be replaced with the recordings of 2 L and N by lumbrical/interossei method in the evaluation of diabetic neuropathies. PMID- 11193542 TI - [A case of moyamoya disease presenting with geographic mislocation, person misidentification and fantastic confabulation]. AB - A 52-year-old woman presented with geographical mislocation (misidentification for place), person misidentification and fantastic confabulation as a result of cerebral infarction. Head MRI demonstrated a focal lesion in the right frontal lobe. Cerebral angiogram demonstrated occlusion in the circle of Willis with moyamoya vessels. The neuropsychological examination revealed memory impairment and frontal lobe dysfunction. The patient's misidentification for place and person as well as confabulation lasted for 1.5 months since admission, then gradually disappeared. We speculate that there existed a common mechanism for these three symptoms; i.e., misidentification and confabulation were based upon the impaired interpretation of the small events and partial objects in the surrounding circumstances, which might interfere with the appropriate integration and judgments of the outside information in general. The impaired monitoring and frontal dysfunction caused by the right frontal lesion appeared to be responsible for causing her deficits. PMID- 11193543 TI - [A case report of chronic myelocytic leukemia with multiple brain metastases, which responded to the gamma-knife therapy]. AB - We report a 78-year-old woman who had multiple leukemic cell tumors in the brain in the course of chronic myelocytic leukemia (CML). As far as we could survey, such brain tumors were extremely rare. She had been followed because of chronic phase of CML until October, 1998, when she noticed muscle weakness in her left upper and lower extremity. A head MRI revealed multiple masses in the brain, a biopsy of which revealed a tumor of CML cells. Although 40 Gy gamma-knife therapy had reduced the size and numbers of brain tumors, we found recurrence of left hemiparesis and tumors three months after the gamma-knife therapy. Whole brain irradiation therapy (total 30 Gy) was somewhat effective to the tumor and hemiparesis transiently subsided. Thereafter her general condition worsened again, and she died in June, 1999, eight months after the diagnosis of the brain tumors of leukemic cells. We had not seen any other clinical evidence of generalized blastic crisis in this patient. In our case, MRI of the brain showed two patterns of metastases, tumor forming and cortical invasive type. We thought that these two patterns of brain involvement might show different responses to the radiation therapy, and it was characteristic in this patient. PMID- 11193544 TI - [A case of hypertrophic cranial pachymeningitis developed skull lesion]. AB - We report a case of hypertrophic cranial pachymeningitis (HCP) developed skull lesion. A 70-year-old male presented with the symptom of left hemiconvulsion. MRI revealed that the enhanced intraosseous mass infiltrated into the the dura and brain parenchyma under the parasagittal region of the right parietal bone. Histological examination revealed chronic inflammation with lymphoplasmacytic infiltrate and fibrosis of both intraosseous mass and dural invasive lesion. Steroid therapy resulted in improvement of clinical symptoms and enhanced lesion of MRI. Three years later, the patient presented with generalized convulsion and weakness of right upper and lower limbs. MRI revealed dural thickening with gadolinium enhancement in the bilateral parasagittal region and falx. Angiography showed occlusion of the superior sagittal sinus. The cause of relapsing symptoms in this patient may have been related to the occlusion of the superior sagittal sinus, due to HCP. We considered that the incipient intraosseous mass resulted from a response of the marrow by destructive progression of chronic inflammation passed through the fracture crack or the cavity of arachnoid granulation. PMID- 11193545 TI - [A case of effective urgent irradiation therapy for metastatic spine tumor]. AB - A 74-year-old man noticed weakness in bilateral lower limbs 2 months prior to admission. The weakness had rapidly progressed and he could not stand by himself on admission. All thoracic vertebral bodies showed mosaic pattern on T 2 weighted image. At Th 10 and Th 11, two enhanced masses compressed spinal cord posteriorly. Basal-serum tumor markers, such as LDH, ALP, total-acid phosphatase and prostatic acid phosphatase were elevated, metastatic spine tumor from prostatic carcinoma was suspected. Biopsy specimen from its prostate revealed low differentiated adenocarcinoma. Because sphincter dysfunction progressed rapidly after admission, we started 3 Gy/day irradiation within 24 hr from its appearance targeting both Th 10 to L 1 vertebral bodies and the prostate in total 30 Gy. The clinical symptoms started to resolve immediately, and the disappearance completely within 7 months. This case illustrated that urgent irradiation was effective for broad metastatic spinal tumor with rapidly progressive neurological deficits. PMID- 11193546 TI - [Small epidermoid induced trigeminal neuralgia unrecognized by conventional CT and MRI for over 25 years]. AB - A 65-year-old woman had been conservatively treated as idiopathic trigeminal neuralgia for over 25 years, because conventional computed tomography (CT) and magnetic resonance imaging(MRI) showed no abnormality in the cerebello pontine(CP) angle cistern. She received a detailed MRI by constructive interference in steady state and diffusion weighted image(DWI) sequences. Those sequences on MRI well demonstrated a epidermoid tumor in the CP angle cistern, and the removal of the tumor completely resolved the neuralgia. Since a small epidermoid in the CP angle cistern seems to be unrecognized by conventional CT and MRI, detailed evaluation by DWI sequence, which has been widespread recently, is required for patients with trigeminal neuralgia. PMID- 11193547 TI - [Anosognosia for hemiplegia in a patient with pontine infarction]. AB - We report a patient with anosognosia for hemiplegia associated with a right pontine infarction. A 51-year-old woman with histories of hypertension and diabetes mellitus was admitted because of weakness of her left upper and lower extremities. On neurologic examination, she was alert and oriented without dementia. Visuospatial hemineglect was not present. Hemiparesis of her left upper and lower extremities was noted. Her brain MRIs showed a large infarction in the right pons. On admission, she could recognize her illness but was indifferent to her hemiplegia, so she said that there was not well-off for her life. Two weeks after the onset, her neurological symptoms gradually improved. Simultaneously, her interest in her hemiparesis increased. We proposed that, in the present patient, anosognosia for hemiplegia was caused by the pontine infarction. Since pontine anosognosia for hemiplegia has been rarely reported to date, it is expected that the findings of the present patient will be useful to the better understanding of mechanisms underlying anosognosia. PMID- 11193548 TI - [3 D-MRA of idiopathic carotid-cavernous fistula]. PMID- 11193549 TI - [Postictal magnetic resonance imaging mimicking the dissemination in patient with anaplastic astrocytoma]. PMID- 11193550 TI - [Current topics on classification and nomenclature of bacteria. 3. The present condition and role of the subcommittees on taxonomy]. PMID- 11193551 TI - [A Shigella sonnei outbreak in Nagasaki]. AB - We have experienced an outbreak of dysentery in Nagasaki. Shigella sonnei were positively cultured from 467 patients out of suspected 821 cases, and 346 patients were admitted. 121 patients were treated with oral antimicrobials in the outpatient clinic. Five patients were diagnosed as secondary infection. We treated a total of 96 patients in Nagasaki Municipal Medical Center, and studied the clinical and bacterial features in these 96 patients. Chief complaints included fever, abdominal pain and diarrhea. Most diarrheal patients showed waterly diarrhea and only a few were bloody (3 of 47). Treatment of levofloxacine 300 mg a day for 5 days successfully eliminated S. sonnei from all culture positive patients. An environmental surveillance revealed that water in a well at the university to which many patients were using was the origin of the infection with positive cultures of S. sonnei. No difference between the clinical and environmental isolates was observed in results on biochemical, serological and enzymatic tests. All isolates were susceptible to levofloxacin and to ofloxacin, but three isolates showed resistance of fosfomycin with MIC above 64 micrograms/ml. In analysis of pulsed-field gel electrophoresis, both clinical and environmental isolates were considered to be closely related. PMID- 11193552 TI - [Comparison of cost and benefits of each model for rubella immunization in Japan]. AB - MMR (measles-mumps-rubella) immunization in Japan was suspended in 1993 due to the high incidence of mumps meningitis as a complication. As a result, immunization coverage for rubella still remains at the 50-60% level in Japan. One way to increase the coverage rate is to increase the frequency of immunization. We calculated the predicted positivity rate of the antibody and cost and the benefits is three models of double vaccination, i.e., vaccination twice. The first model consists of simply two identical vaccinations. The second model consists of two vaccinations with mass vaccination at school for the second immunization. The third model consists of two vaccinations with screening of the urinary antibody for rubella in the second immunization. To calculate the predicted values we used coefficients from Ibara City. The predicted positivity rates and cost increases ranged from 60% to 90% and from 7.3 billion to 12.8 billion yen from the first to third models, respectively. Screening for the urinary antibody should be much cheaper than the presumed price because more than a million subjects will be screened. Since it would cost less than half the price, the third model should be best for the positivity rate of the antibody and cost and benefits. Therefore, we think that third model is the best correction until MMR immunization can be reintroduced. PMID- 11193553 TI - [Comparison of the morphology and the reactivity of Chlamydia pneumoniae isolated in north-Kanto Area, Ibaraki Prefecture, Japan]. AB - To compare the morphology among Chlamydia pneumoniae (C. pneumoniae), strain TW183 and strains which were isolated in the area of Kasumigaura, Ibaraki from 1992 to 1995. C. pneumoniae were infected on HL cell monolayers and cultured in 5% CO2 at 35.5 degrees C for about 60 hrs. The cells were harvested and fixed with 2.5% glutaraldehyde, and then the regular procedure for observation of Chlamydia in inclusion by transmission electron microscope was performed. Immunoblot assay was carried out by using highly and partially purified C. pneumoniae TW183 and 4 isolates with partial purification as antigens. The results were as follows: the shape of TW183 and the isolates included pear and round shapes, respectively. Immunoblotting profiles were the same in terms of band-formation patterns with the serum from a patient infected with C. pneumoniae. These results may indicate that the round shape of C. pneumoniae elementary body (EB) is predominantly pandemic in Japan, although pear-shaped EBs of C. pneumoniae were found in the neighboring prefecture of Chiba. PMID- 11193554 TI - [Virucidal activity of disinfectants: virucidal activities of disinfectants on some viruses coated on several materials and its durability]. AB - First, four disinfectants were tested for virucidal activity on viruses coated upon materials. Disinfectants of the aldehyde and halogen groups had a destructive effect on both enveloped and non-enveloped DNA and RNA viruses coated on a cotton gauze, stainless chips, wood shavings, polyplopylene resin chips and latex resin chips, respectively. Disinfectant of the biguanide group had a virucidal activity on both enveloped DNA and RNA viruses. Secondary, five disinfectants were tested for the durability of their virucidal activity on two DNA and RNA viruses after preparing working solutions. The disinfectants of the aldehyde group maintained their virucidal efficiency for 2 to 3 days. Disinfectants of the invert and amphoteric soap groups, the biguanide group and the halogen group maintained their virucidal efficiency for 1 to 2 days. In the presence of bovine serum, the virucidal activity of the aldehyde group and the halogen group were not influenced but that of the invert and amphoteric soap groups were strongly influenced and lost their effect. PMID- 11193555 TI - [Clinical evaluation of rapid diagnostic kit detecting separately influenza A and B viruses]. AB - The Directigen Flu A + B kit, a rapid diagnostic device for influenza virus A and B was evaluated. The nasopharyngeal aspirates were obtained from 239 patients who visited our hospital, between January and March, 2000, presenting flu-like symptoms. Influenza virus AH1: 77 and AH3: 51 were isolated from 128 specimens and none from 111 specimens. Directigen Flu A + B showed 115 specimens positive and 106 specimens negative. The sensitivity and specificity of this kit were 89.8% (115/128) and 95.5% (106/111) compared with viral isolation. Agreement on positive and negative interpretations between Direction Flu A and this kit was 97.9% (234/239). In the evaluation of this kit for influenza B virus, 60 frozen nasopharyngeal aspirates collected from February to April, 1999 were used. The sensitivity and specificity of this kit were 88.9% (16/18) and 88.1% (37/42) compared with viral isolation. Agreement on positive and negative interpretations between FLU OIA and this kit was 91.7% (55/60). The Directigen A + B demonstrated sensitivity and specificity equivalent to the conventional kits in nasopharingeal aspirates. This kit can also differentiate influenza A and B viruses, a feature which is useful for treatment using anti-viral agents such as amantadine and neuraminidase inhibitor. To date, the kit is the most effective tool for the rapid diagnosis of influenza. PMID- 11193556 TI - [Sensitivity and specificity of rapid diagnosis kit detecting separately influenza A and B viruses]. AB - Sensitivity and specificity of the Directigen Flu A + B kit, a rapid test for influenza virus A and B, were evaluated. This test detects influenza A and B viruses separately by EIA. Reactivity of the kit was tested using a total of 23 isolates: 13 isolates of human influenza virus A (H1N1, H3N2) and 10 isolates of human influenza virus B. All of the isolates were tested positive and no difference in reactivity was found in antigenic variables and subtypes. The kit was only reactive to influenza virus A and B, not reactive to other viruses. Typical influenza A and B strains were tested for detection limit. 7.8 x 10(3) pfu/ml was a detection limit for influenza virus A (H1N1: Beijing/262/95), 4.7 x 10(4) pfu/ml for influenza virus A (H3N2: Kitakyusyu/159/93), and 3.1 x 10(4) pfu/ml for influenza virus B (Guangdong/05/94). The Directigen Flu A + B kit was a easy-to-use, rapid detection device and the kit has sensitivity and specificity equivalent to other diagnostic devices, suggesting the kit are useful in medical institutions. PMID- 11193557 TI - [Clinical efficacy and safety of the selective oral neuraminidase inhibitor oseltamivir in treating acute influenza--placebo-controlled double-blind multicenter phase III trial]. AB - We conducted the placebo-controlled double-blind multicenter Phase III trial of newly developed selective oral neuraminidase inhibitor, oseltamivir phosphate (Ro64-0796), in order to evaluate the efficacy and safety, when Ro64-0796 was administered orally to both type A and type B influenzavirus infected patients. Patients were randomly assigned to either Ro64-0796 75 mg twice daily group or matching placebo group for five days. A total of 316 patients (Ro64-0796 group; 154 and placebo group; 162) were recruited, and intent-to-treat infected population, which was defined as the patients that study drug was administered one or more and laboratory-confirmed influenzavirus infection was demonstrated, were 122 and 130, respectively. Ro64-0796 decreased significantly median viral titers after 72 hours (p = 0.0009. Analysis of covariance), indicating the rapid inhibition of virus replication, and duration of illness which was primary variable of efficacy, was reduced statistically significant by one day (23.3 hours) (p = 0.0216, generalized Wilcoxon test). Ro64-0796 treatment also resulted in the reduction of the fever duration and severity of clinical symptoms. Concerning the safety evaluation, the main accompanied symptoms with Ro64-0796 application were gastrointestinal disorders such as bellyache, nausea and vomiting. Most of these events were mild and allowable for the clinical use. There was no abnormal change attributable to Ro64-0796 application in the clinical laboratory tests as well as the physiological tests. Our data suggests that Ro64-0796 is useful in treating the acute influenzavirus infection. PMID- 11193559 TI - [Two cases of HIV infection accompanied with borderline personality disorder]. AB - We report here two cases of HIV infection with a borderline personality disorder. Case 1 was a 25-year-old male patient who was diagnosed with HIV infection 4 years ago. Borderline personality disorder was also diagnosed at that time. Although he was referred to our hospital in 1999, we had to refer him to another hospital for his regular outpatient hemodialysis. Case 2 was a 24-year-old male patient who had borderline personality disorder since 1996. He was diagnosed with HIV infection in 1999 and referred to our hospital. He ignored rules in visiting clinics such as prior reservations and frequently called doctors, case-workers and nurses. After several visit he intentionally took excessive sedative medicines and called a case-workers at our hospital. He was admitted to our hospital for three days. After he was discharged, we set limitations for his behavior not to harm himself and to obey the rules in visiting clinics. In other countries investigators report that borderline personality disorder is more common in HIV-infected persons. It may be because persons with borderline personality disorder are more likely to engage in high-risk sexual behavior, which is also applicable to these two cases. As HIV infection is rapidly prevailing in Japan, it is possible that the chance are that this disorder will be seen more frequently in HIV infected cases. PMID- 11193558 TI - [Efficacy and safety of the selective oral neuraminidase inhibitor oseltamivir for prophylaxis against influenza--placebo-controlled double-blind multicenter phase III trial]. AB - We have investigated the long-term prophylactic efficacy and safety of oseltamivir phosphate (Ro64-0796), an orally bioavailable prodrug of novel, potent and selective type A and type B influenzavirus neuraminidase inhibitor, when Ro64-0796 was administered orally to the healthy volunteers. Participants older than 16 year-old were randomly assigned to either Ro64-0796 75 mg once daily group or matching placebo group for six weeks. A total of 308 participants (Placebo group; 153 and Ro64-0796 group; 155) were enrolled in this trial. The primary variable of efficacy, incidence of laboratory-confirmed influenzavirus infected subjects accompanied by both fever of 37.5 degrees C or higher and at least two influenza symptoms (group 1) were 1.3% in Ro64-0796 group in contrast with 8.5% in placebo group, inducing 85% inhibition of infection (p = 0.00323, Fisher's exact test). As secondary variable, incidence of laboratory-confirmed influenzavirus infected subjects who lack either fever (37.5 degrees C or higher) or at least two influenza symptoms (group 2) and incidence of asymptomatic infected subjects (group 3) were tend to decrease in Ro64-0796 group, and finally cumulative inhibition rate was 76% in group 1 + 2 combined (p = 0.000891. Fisher's exact test), and 63% in group 1 + 2 + 3 combined (p = 0.002150, Fisher's exact test). As for the safety evaluations, Ro64-0796 was well tolerated but was associated with gastrointestinal disorders such as nausea and vomiting which were mild and allowable for the clinical use. There was no abnormal change attributable to Ro64-0796 application in the clinical laboratory tests as well as the physiological tests. Our results demonstrate that oseltamivir is safe and effective for the prevention of influenza. PMID- 11193560 TI - [A case of pyogenic vertebral osteomyelitis caused by Haemophilus aphrophilus]. AB - On Aug. 3, 1999, a 73-year-old male was admitted to our hospital with the chief complaint of pain in the neck, high fever, and numbness in the arm. MRI of the cervix showed high intensity at the C3/C4 disc space. Laboratory data showed several signs of inflammation. Haemophilus aphrophilus was detected from the specimen of the disc space, and the diagnosis of pyogenic vertebral osteomyelitis caused by H. aphrophilus was made. After the identification of H. aphrophilus, antibiotic therapy with Cefotiam (2 g/day) was given but his vertebral collapsed. Surgical treatment consisted of curettage and anterior spinal body fusion using the iliac bone, was performed on his 23rd hospital day, successfully. The antibiotic therapy of Cefazolin (2 g/day) was continued for the first 3 days, followed by Cefotiam (2 g/day) and later Levofloxacin (300 mg/day). The patient was discharged on the 88th hospital day. The origin of infecting H. aphrophilus in this patient was not clear, but oral source was suspected. We reported the first case of pyogenic vertebral osteomyelitis caused by H. aphrophilus in Japan. PMID- 11193561 TI - Expression and function of Na+HCO3- cotransporters in the gastrointestinal tract. AB - The stomach, duodenum, colon, and pancreas secrete HCO3- ions into the lumen. Although the importance of HCO3- secretion for the maintenance of mucosal integrity, a normal digestion, and the reabsorption of Cl- has been well established, the molecular nature of the apical and basolateral HCO3- transporting proteins has remained largely unknown. Functional studies have suggested that a Na+HCO3- cotransport system, similar but not identical to the well-characterized Na+HCO3- cotransporter in the basolateral membrane of the kidney proximal tubule, is present in duodenal and colonic enterocytes, pancreatic ducts cells, and gastric cells and involved in HCO3- uptake from the interstitium. This report describes our work towards understanding the molecular nature, cellular origin, and functional relevance of the Na+HCO3- cotransporter(s) in the stomach and intestine and reviews work by others on the function and localization of Na+HCO3- cotransport processes in the gastrointestinal tract. PMID- 11193562 TI - Epithelial transport and barrier function: pathomechanisms in gastrointestinal disorders. Proceedings of a conference. March 26-27, 1999. Berlin, Germany. PMID- 11193563 TI - Tumor necrosis factor-alpha potentiates ion secretion induced by muscarinic receptor activation in the human intestinal epithelial cell line HT29cl.19A. PMID- 11193564 TI - Investigation of motility and secretion in perfused guinea pig colon ex situ. PMID- 11193565 TI - Stimulation by portal insulin of intestinal glucose absorption via hepatoenteral nerves and prostaglandin E2 in the isolated, jointly perfused small intestine and liver of the rat. AB - Insulin infused into the portal vein acutely enhanced intestinal glucose and galactose absorption via the sodium-dependent glucose cotransporter-1 in the isolated, jointly perfused small intestine and liver of the rat. Atropine and tetrodotoxin infused into the superior mesenteric artery completely prevented the portal insulin-dependent increase in intestinal glucose absorption, and carbachol caused an increase similar to that of portal insulin. Thus, a signal was transmitted against the bloodstream in a retrograde direction from the portal vein to the small intestine via hepatoenteral cholinergic nerves. The intracellular messenger in the enterocytes was cAMP, and the link between the muscarinic receptors, which do not increase cAMP concentrations, and adenylate cyclase was found to be prostaglandin E2. PMID- 11193566 TI - Effects of HIV protease inhibitors on barrier function in the human intestinal cell line HT-29/B6. PMID- 11193567 TI - Induction of endothelial barrier function in vitro. PMID- 11193568 TI - The structure and function of claudins, cell adhesion molecules at tight junctions. AB - Tight junctions (TJs) play a pivotal role in compartmentalization in multicellular organisms by sealing the paracellular pathway in epithelial and endothelial cell sheets. Recently, novel integral membrane proteins, claudins, have been identified as major cell adhesion molecules working at TJs. Claudins comprise a multigene family, and each member of approximately 23 kDa bears four transmembrane domains. To date, 15 members of this gene family have been identified. When expression vectors of each species of claudins were transfected into fibroblasts lacking endogenous claudins or TJs, well-developed TJs were observed between adjacent transfectants. Furthermore, claudins were shown to be directly involved in the barrier function of TJs by experiments using Clostridium perfringens enterotoxin. Now that claudins have been identified, the structure and functions of TJs should be determined in detail in molecular terms. PMID- 11193569 TI - Intestinal cell adhesion molecules. Liver-intestine cadherin. AB - The cadherin superfamily comprises a large number of cell adhesion molecules, several of which are expressed in the gastrointestinal tract. LI-cadherin represents a novel type of cadherin within the cadherin superfamily distinguished from other cadherins by structural and functional features described in this review. In the mouse and human, LI-cadherin is selectively expressed on the basolateral surface of enterocytes and goblet cells in the small and large intestine, whereas in the rat this cadherin is additionally detectable in hepatocytes. LI-cadherin is capable of mediating Ca(2+)-dependent homophilic cell cell adhesion independent of interactions with the cytoskeleton, indicating that the adhesive function of this novel cadherin is complementary to that of E cadherin and desmosomal cadherins co expressed in the intestinal mucosa. PMID- 11193570 TI - Molecular diversity of plaques of epithelial-adhering junctions. AB - In biochemical and immunocytochemical comparisons of adhering junctions of different epithelia, we have observed differences in molecular composition not only between the intermediate filament-attached desmosomes and the actin filaments-anchoring adherens junctions but also between desmosomes of different tissues and of different strata in the same stratified epithelium. In addition we now report cell type-specific differences of molecular composition and immunoreactivity in both desmosomes and adherens junctions of certain simple epithelia. Whereas the zonula adhaerens of human intestinal and colonic epithelial cells, and of carcinomas derived therefrom, contains the additional armadillo-type plaque protein ARVCF, this protein has not been detected in the zonula adhaerens of hepatocytes. Similarly, plakophilin 3 is present in the desmosomal plaques of intestinal and colonic cells but appears to be absent from the hepatocytic desmosomes. We suggest that these profound compositional differences in the junctions of related simple epithelia are correlated to functional differences of the specific type of epithelium. PMID- 11193571 TI - Characterization and molecular localization of anion transporters in colonic epithelial cells. AB - This study describes the identification and characterization of anion transporters in apical membrane (APM) and basolateral membrane (BLM) of rat distal colon. Cl-HCO3, Cl-OH, Cl-butyrate, and butyrate-HCO3 exchanges and Na HCO3 cotransporter are present in rat distal epithelial cells. Cl-HCO3 exchange (1) is present only in APM from surface, but not from crypt cells; (2) is also present in BLM; and (3) of surface cell is encoded by anion exchange (AE)-1 isoform, whereas BLM Cl-HCO3 is encoded by AE2 isoform. Cl-OH exchange is present only in APM, but not in BLM from surface and crypt cells, and is responsible for regulation of cell functions (i.e., cell pH and cell volume regulation). Butyrate HCO3 exchange (1) is also present in apical membrane vesicles (AMV) from surface, but not from crypt cells; (2) is present in BLM; and (3) is responsible for SCFA dependent HCO3 secretion. By contrast, Cl-butyrate exchange: (1) is present in APM from both surface and crypt cells; (2) is not present in BLM; and (3) recycles butyrate by absorbing Cl. Na-HCO3 cotransport: (1) is present only in BLM; (2) is expressed predominantly in midcrypt regions; and (3) may be linked to HCO3 secretion. A mechanism for HCO3 movement across the crypt apical membrane has not as yet been identified. PMID- 11193572 TI - Neutrophil migration across intestinal epithelium. AB - Transmigration of neutrophils across epithelial surfaces is the hallmark of inflammatory mucosal diseases of diverse organs. In disorders such as Crohn's disease, ulcerative colitis, pyelonephritis, and bronchitis, for example, neutrophil transmigration correlates with clinical disease activity, is associated morphologically with injury to the epithelium, and is central to disease pathophysiology. The mechanisms by which neutrophils transmigrate across epithelia are, therefore, of considerable significance for numerous pathologic states. In this paper, we discuss current evidence that defines these mechanisms in intestinal epithelium, emphasizing the structural constituents determining adhesive interactions and a subset of the complex regulatory signals between neutrophils and epithelium. PMID- 11193574 TI - Role of M cells in intestinal barrier function. AB - M cells are known as specialized epithelial cells of the follicle-associated epithelium of the gastrointestinal tract. As M cells have a high capacity for transcytosis of a wide range of microorganisms and macromolecules, they are believed to act as an antigen sampling system. The primary physiological role of M cells seems to be the rapid uptake and presentation of particular antigens and microorganisms to the immune cells of the lymphoid follicle to induce an effective immune response. In contrast to absorptive enterocytes, M cells do not exert direct defense mechanisms to antigens and pathogens in the gut lumen. Therefore, they provide functional openings of the epithelial barrier. Although M cells represent a weak point of the epithelial barrier, even under noninflamed conditions, there seems to be a balance between antigen uptake and immunological response. The low number of M cells in the gastrointestinal tract and the direct contact to immune cells in the lamina propria usually prevent the occurrence of mucosal inflammation. During chronic intestinal inflammation we observe an increase of M cell number and apoptosis selectively in M cells. M cell damage seems to be responsible for the increase of the uptake of microorganisms that is observed during intestinal inflammation. Under inflammatory conditions in the intestine, the maintenance of the epithelial barrier is broken and M cells seem to play a major role during this process. PMID- 11193573 TI - Expression and function of death receptors and their natural ligands in the intestine. AB - The tumor necrosis factor receptor (TNFR) family is a still-growing group of homologous transmembrane proteins, some of which bear an intracellular "death domain" and are able to directly mediate apoptosis. Apoptosis is induced upon trimerization of the receptors by their natural ligands' constituting the complementary TNF family. The best-characterized apoptosis-mediating TNFR family member is CD95 (APO-1/Fas). CD95 is functionally expressed on the basolateral surface of colonic epithelial cells regardless of their position along the crypt axis. The biological significance of this CD95 expression in the gut, however, is still under discussion. Although it is unlikely that the CD95/CD95L system is involved in the physiologic regeneration of the intestinal epithelium, this system may play an important role in the pathogenesis of inflammatory bowel diseases. In contrast to the normal epithelium, colon carcinoma cell lines are mostly resistant to CD95-induced apoptosis. The detection of CD95L expression in colon carcinoma cell lines has led to the concept of carcinomas as "immunoprivileged sites," where invading immune cells are killed by CD95L expressing tumor cells. A more recently described member of the TNF family is TRAIL, which is also able to induce apoptosis. As yet, four TRAIL receptors have been cloned, two of which (TRAIL-R1 and 2) bear a death domain and mediate apoptosis, whereas two others (TRAIL-R3 and 4) lack (functional) death domains and are supposed to act as decoy receptors. Because many tumor cell lines in vitro are sensitive to TRAIL-induced apoptosis while their normal counterparts are not, TRAIL is currently under discussion as a possible anticancer therapeutic agent. PMID- 11193575 TI - Nutrient transporter function studied in heterologous expression systems. AB - Although a large number of plasma cell nutrient transport proteins has been cloned in the last couple of years, much remains to be learned about their structure-function relationships, membrane topology, posttranslational regulation, and bioenergetics of transport. Major progress in the study of the human and animal transporters has come from heterologous expression systems, which offer the benefits of ease of genetic selection and manipulation, short generation time of the organisms in which transporters are expressed, and comparatively high levels of expression of the recombinant proteins. Because our main focus is mammalian peptide transporters, the intestinal peptide transporter, PEPT1, and its renal counterpart, PEPT2, will serve here as models for the analysis of their structure and function when they are heterologously expressed in different cell systems. PMID- 11193576 TI - Epithelial barrier defects in HT-29/B6 colonic cell monolayers induced by tumor necrosis factor-alpha. AB - The barrier function of intestinal epithelia relies upon the continuity of the enterocyte monolayer and intact tight junctions. After incubation with tumor necrosis factor-alpha TNF-alpha, however, the number of strands that form the tight junctions decreases, and apoptosis is induced in intestinal epithelial cells. These morphological changes lead to a rise of transepithelial ion permeability, because the paracellular ion permeability increases and leaks associated with sites of apoptosis increase by number and magnitude. Thus apoptosis and degradation of tight junctions contribute to the increased permeability observed after exposure to TNF-alpha. These mechanisms explain clinical manifestations in the inflamed intestinal wall containing cytokine secreting macrophages--for example, leak flux diarrhea and invasion of bacterial enterotoxins. PMID- 11193577 TI - Enhanced expression of iNOS in inflamed colons of IL-2-deficient mice does not impair colonic epithelial barrier function. AB - On the basis of recently observed high levels of iNOS expression that correlated with intestinal inflammation in interleukin-2-deficient [IL-2(-/-)] mice, it was postulated that nitric oxide may damage colonic epithelial cells or impair intestinal epithelial barrier function. This damage may result in an increased permeability of the colonic epithelium leading to high antigenic exposure of the intestinal immune system, which may perpetuate chronic inflammation. Our data demonstrate that high expression of iNOS in IL-2(-/-) mice is correlated with the length/weight ratio (L/W ratio), a widely accepted marker for intestinal inflammation. However, no reduction of epithelial resistance was observed, as would be expected in case of a damaged, leaky epithelium. Our results suggest that enhanced formation of NO in IL-2(-/-) mice does not cause impairment of epithelial barrier function. PMID- 11193578 TI - Regulation of intercellular tight junctions by zonula occludens toxin and its eukaryotic analogue zonulin. AB - The intestinal epithelium represents the largest interface between the external environment and the internal host milieu and constitutes the major barrier through which molecules can either be absorbed or secreted. There is now substantial evidence that tight junctions (tj) play a major role in regulating epithelial permeability by influencing paracellular flow of fluid and solutes. Tj are one of the hallmarks of absorptive and secretory epithelia. Evidence now exists that tj are dynamic rather than static structures and readily adapt to a variety of developmental, physiological, and pathological circumstances. These adaptive mechanisms are still incompletely understood. Activation of PKC either by Zonula occludens toxin (Zot) or by phorbol esters increases paracellular permeability. Alteration of epithelial tj is a recently described property for infectious agents. Clostridium difficile toxin A and B and influenza and vesicular stomatitis viruses have been shown to loosen tj in tissue culture monolayers. Unlike what occurs after the Zot stimulus, these changes appear to be irreversible and are associated with destruction of the tj complex. On the basis of this observation, we postulated that Zot may mimic the effect of a functionally and immunologically related endogenous modulator of epithelial tj. We were able to identify an intestinal Zot analogue, which we named zonulin. It is conceivable that the zonulins participate in the physiological regulation of intercellular tj not only in the small intestine, but also throughout a wide range of extraintestinal epithelia as well as the ubiquitous vascular endothelium, including the blood-brain barrier. Disregulation of this hypothetical zonulin model may contribute to disease states that involve disordered intercellular communication, including developmental and intestinal disorders, tissue inflammation, malignant transformation, and metastasis. PMID- 11193579 TI - Analysis of low-molecular-weight GTP-binding proteins in two functionally different intestinal epithelial cell lines. AB - Low molecular weight GTP-binding proteins are molecular switches that are believed to play pivotal roles in cell growth, differentiation, cytoskeletal organization, and vesicular trafficking. In this study, for the first time, members of this family of proteins in two functionally different intestinal epithelial cell lines are identified and characterized. [alpha-32P]GTP blot overlay assays of cytosolic and membranous fractions revealed the presence of specific GTP-binding proteins in the range of 20-30 kDa (small GTPases) in both fractions, with considerably higher amounts in the membranous insoluble fraction. Analysis by two-dimensional electrophoresis, immunoprecipitation using monoclonal and sequence-specific polyclonal antibodies, and C3 exoenzyme-mediated ADP ribosylation demonstrated the presence of Ras, Rap, Rho, Rac, Rab, and several other small GTPases. The pattern of small GTP-binding proteins corresponded to the characteristics of the cell lines. Caco-2 cells showed a Rab5 protein that is known to be involved in endocytosis but was not found in T84 cells. On the contrary Rab3 has been shown to participate in secretory processes. It is highly expressed in T84 cells (sixfold compared to Caco-2 cells). PMID- 11193580 TI - Increased tight junction permeability can result from protein kinase C activation/translocation and act as a tumor promotional event in epithelial cancers. AB - Exposure of LLC-PK1 epithelial cell cultures to phorbol ester tumor promoters causes immediate translocation of protein kinase C-alpha (PKC-alpha) from cytosolic to membrane-associated compartments. With a very similar time course, a dramatic and sustained increase in tight junctional (paracellular) permeability occurs. This increased permeability extends not only to salts and sugars but macromolecules as well. Fortyfold increases of transepithelial fluxes of biologically active EGF and insulin occur. Recovery of tight junction barrier function coincides with proteasomal downregulation of PKC-alpha. The failure to downregulate activated membrane-associated PKC-alpha has correlated with the appearance of multilayered cell growth and persistent leakiness of tight junctions. Accelerated downregulation of PKC-alpha results in only a partial and transient increase in tight junction permeability. Transfection of a dominant/negative PKC-alpha results in a slower increase in tight junction permeability in response to phorbol esters. In a separate study using rat colon, dimethylhydrazine (DMH)-induced colon carcinogenesis has been preceded by linear increases in both the number of aberrant crypts and transepithelial permeability, as a function of weeks of DMH treatment. Adenocarcinomas of both rat and human colon have been found to have uniformly leaky tight junctions. Whereas most human colon hyperplastic and adenomatous polyps contain nonleaky tight junctions, adenomatous polyps with dysplastic changes did possess leaky tight junctions. Our overall hypothesis is that tight junctional leakiness is a late event in epithelial carcinogenesis but will allow for growth factors in luminal fluid compartments to enter the intercellular and interstitial fluid spaces for the first time, binding to receptors that are located on only the basal-lateral cell surface, and causing changes in epithelial cell kinetics. Tight junctional leakiness is therefore a promotional event that would be unique to epithelial cancers. PMID- 11193581 TI - Stress-induced decrease of the intestinal barrier function. The role of muscarinic receptor activation. AB - Recently the breakdown of the barrier function of the intestinal epithelium after application of an experimental psychological and physical stress protocol in rats has been observed. Not only did smaller molecules pass from the luminal to the serosal side, but so also did larger proteins with the dimensions of luminal antigens and toxins. The increased permeability for macromolecules is primarily due to a decrease of the tightness of the zonula occludens, but an increased endocytotic uptake indicates that transcytosis is increased also. From studies of model systems it can be concluded that activation of the intracellular protein kinase C route by muscarinic receptor activation or histamine receptor activation can be one of the underlying cellular pathways. The physical pathway relaying the stress from the brain to the intestinal tract appears to be the parasympathetic branch of the autonomic nervous system. The difference in reaction of different strains suggests that coping style is an important determinant of the response of the intestinal barrier to stress. PMID- 11193582 TI - Immunologically mediated transport of ions and macromolecules. AB - There is increasing evidence supporting the involvement of immune cells and mediators in the control of intestinal physiology. Cell coculture systems and epithelial cell lines have provided convenient model systems for the study of immunomodulation of epithelial function. Abundant cytokines and immune mediators have been shown to directly or indirectly alter epithelial transport of ions and macromolecules. Animal models of hypersensitivity have shown that luminal antigen challenge in the intestine of sensitized rats induces a rapid ion secretory response due to enhanced transepithelial transport of antigen. Transport of ions and macromolecules is highly regulated and an important component of host defense. Dysregulation of epithelial function may play a role in several intestinal disorders, such as inflammatory bowel diseases and food allergy. PMID- 11193583 TI - Carbachol-induced Ca2+ entry into rat colonic epithelium. PMID- 11193584 TI - Effects of endotoxin on human large intestine. PMID- 11193585 TI - Increased paracellular macromolecular transport and subnormal glucose uptake in duodenal biopsies of patients with microvillus inclusion disease. Comparisons to other chronic diarrhea patients and to nondiarrhea patients. PMID- 11193586 TI - Apoptosis and intestinal barrier function. AB - The signal transduction pathways of the induction of apoptosis in the gastrointestinal tract have in part been discovered. However, almost nothing is known about the functional influence of apoptotic signals on intestinal barrier function. In this study the effect of camptothecin-induced apoptosis in HT-29/B6 monolayers and the influence of apoptosis on epithelial barrier function were characterized. We demonstrated that camptothecin causes a decrease of transepithelial resistance and an increase in fluxes of the paracellular marker [3H]mannitol. Camptothecin increased the apoptotic rate and the conductance of single-cell apoptosis as measured by the conductance scanning technique. We conclude that in our model of HT-29/B6 cells camptothecin is a potent inductor of apoptosis that causes significant barrier defects measured by the Ussing chamber technique and the conductance scanning technique. Based on these results we are able to investigate the effect of other cytokines--TGF-beta, for instance, and its role in apoptotic conditions. PMID- 11193587 TI - p53-independent apoptosis induced by menadione in the human colon carcinoma cell line Caco-2. PMID- 11193588 TI - Epidermal growth factor, polyamines, and epithelial remodeling in Caco-2 cells. PMID- 11193589 TI - Effect of TNF alpha and IFN gamma on epithelial barrier function in rat rectum in vitro. PMID- 11193590 TI - Colectomy and ileal pouch. Transport and barrier in pouchitis. PMID- 11193591 TI - Mechanisms of epithelial barrier impairment in HIV infection. AB - Diarrhea and malabsorption due to intestinal dysfunction are common symptoms in HIV infection. The pathophysiologic mechanisms of these alterations are often not known, and the role of HIV per se is still controversially discussed. We measured the epithelial transport and barrier function by means of a miniaturized Ussing chamber system in the duodenum of HIV-infected patients in different disease stages, determined by the CD4 cell count in the serum as well as symptoms in patients with and without diarrhea. We could show that diarrhea induced by HIV per se is caused by a leak flux mechanism due to impaired epithelial barrier function. Antisecretory therapy does not seem to be useful in these patients, because we did not find increased active ion secretion. Along the course of the HIV infection, the epithelial transport and barrier function varies with HIV disease stage (expressed by CD4 cell status). In addition, an in vitro model was studied to characterize the effect of HIV-infected human immune cells on the epithelial barrier function using the human colonic epithelial cell line HT 29/B6. HIV infection of human immune cells induced an increase in cytokine release--for example, TNF-alpha, IL-1 beta, IFN-alpha, and IFN-gamma- downregulating the epithelial barrier function of the human colonic epithelial cell line HT-29/B6. Taken together we postulate a specific stage-dependent cytokine pattern released from HIV-infected immune cells in the mucosa, which, corresponding to the HIV disease stage, is responsible for the variation in epithelial function. PMID- 11193593 TI - Cytokine-induced alteration of the epithelial barrier to food antigens in disease. AB - The alteration of the intestinal epithelial barrier is often a consequence of various intestinal diseases but may also be the starting point of these diseases. Undigested food antigens are transported across the intestinal epithelium by a transcytotic mechanism, including a processing within the enterocytes, and leading to the passage of intact proteins, peptides, and amino acids to the underlying mucosa. Inflammation and infection lead to the upregulation of the transport and processing of food proteins; for example, IFN gamma increases the rate of transcytosis and alters, like TNF alpha, the tight junction permeability. Infection of gastric digestive epithelia with Helicobacter pylori also increases the antigenic load transmitted to the underlying immune system by inhibiting the enterocytic lysosomal degradation of proteins. In allergic diseases, such as cow's milk allergy, TNF alpha may be involved in the intestinal dysfunction and the associated enteropathy. PMID- 11193592 TI - Short-term regulation of NHE3 by EGF and protein kinase C but not protein kinase A involves vesicle trafficking in epithelial cells and fibroblasts. AB - NHE3 is an intestinal epithelial isoform Na+/H+ exchanger that is present in the brush border of small intestinal, colonic, and gallbladder Na(+)-absorbing epithelial cells. NHE3 is acutely up- and downregulated in response to some G protein-linked receptors, tyrosine kinase receptors, and protein kinases when studied in intact ileum, when stably expressed in PS120 fibroblasts, and in the few studies reported in the human colon cancer cell line Caco-2. In most cases this is due to changes in Vmax of NHE3, although in response to cAMP and squalamine there are also changes in the K'(H+)i of the exchanger. The mechanism of the Vmax regulation as shown by cell surface biotinylation and confocal microscopy in Caco-2 cells and biotinylation in PS120 cells involves changes in the amount of NHE3 on the plasma membrane. In addition, in some cases there are also changes in turnover number of the exchanger. In some cases, the change in amount of NHE3 in the plasma membrane is associated with a change in the amount of plasma membrane. A combination of biochemical studies and transport/inhibitor studies in intact ileum and Caco-2 cells demonstrated that the increase in brush border Na+/H+ exchange caused by acute exposure to EGF was mediated by PI 3 kinase. PI 3-kinase was also involved in FGF stimulation of NHE3 expressed in fibroblasts. Thus, NHE3 is another example of a transport protein that is acutely regulated in part by changing the amount of the transporter on the plasma membrane by a process that appears to involve vesicle trafficking and also to involve changes in turnover number. PMID- 11193594 TI - Epithelial barrier and transport function of the colon in ulcerative colitis. PMID- 11193595 TI - Diarrhea in ulcerative colitis. The role of altered colonic sodium transport. AB - In normal human colon, water and sodium (Na+) absorption are directly related. Defective Na+ absorption may therefore be an important factor in the pathogenesis of diarrhea in ulcerative colitis (UC). Electrophysiological studies have revealed profound decreases in channel-mediated apical Na+ entry and Na(+)-K(+) ATPase-mediated basolateral Na+ extrusion in surface epithelial cells in inflamed human distal colon. Recent molecular biological studies indicate that mucosal inflammation in UC leads to significant decreases in Na+ channel beta- and gamma subunit expression in the apical membrane of surface colonocytes, with a marked reduction in the levels of beta- and gamma-subunit-specific mRNAs. In addition, basolateral expression of the Na(+)-K(+)-ATPase alpha 1-isoform is reduced along the surface cell-crypt cell axis in UC, although there is no change in the level of the corresponding mRNA. Diarrhea in ulcerative colitis is therefore related, at least in part, to a major defect in electrogenic Na+ absorption, which reflects changes in the levels of expression of critical subunits of both the apical Na+ channel and basolateral Na(+)-K(+)-ATPase. PMID- 11193596 TI - Barrier dysfunction and Crohn's disease. AB - Crohn's disease is a debilitating illness of unknown etiology. A current hypothesis of disease pathogenesis suggests that this illness represents an abnormal immunological reaction to a luminal antigen. As part of this theory it is suggested that the luminal antigen is delivered to the mucosal immune system by a paracellular route. If this theory is correct several testable predictions can be made. In this manuscript these predictions are presented and the evidence to support or refute them is presented. PMID- 11193597 TI - Mechanisms of cholera toxin-induced diarrhea. AB - In the pathogenesis of cholera, cyclic adenosine monophosphate, 5 hydroxytryptamine, prostaglandins, and the function of neuronal structures have been implicated. To elucidate the role of different isoforms of cyclooxygenase (COX)-1 and COX-2, selective COX-2 inhibitors were used. The selective COX-2 inhibitors NS-398 and DFU completely suppressed cholera toxin-induced prostaglandin E2 biosynthesis and caused a dose-dependent inhibition of cholera toxin-induced fluid secretion in the rat jejunum in vivo. Constitutive expression of COX-1 but also of COX-2 mRNA was found in mucosal scrapings of the rat jejunum. Cholera toxin had no effect on COX-1 as well as COX-2 mRNA expression. Treatment of rats with dexamethasone did not effect cholera toxin-induced prostaglandin E2 biosynthesis and did not influence the expression of COX-2 mRNA, further substantiating that cholera toxin does not cause an induction of COX-2 mRNA. Treatment of rats with E. coli lipopolysaccharide caused a marked increase in COX-2 mRNA expression that was inhibited by dexamethasone. In conclusion, the results provide evidence that cholera toxin, in addition to other mediators, uses prostaglandin E2 to exert its secretory effect and that in the case of cholera toxin prostaglandins are metabolized via COX-2. PMID- 11193598 TI - Effects of Clostridium difficile toxins on epithelial cell barrier. AB - Clostridium difficile is the primary agent responsible for many patients with antibiotic-associated diarrhea and almost all patients with pseudomembranous colitis following antibiotic therapy. C. difficile infection is the most frequent form of colitis in hospitals and nursing homes and affects millions of patients in the United States and abroad. The first event in the pathogenesis of C. difficile infection involves alterations of the indigenous colonic microflora by antibiotics, followed by colonization with C. difficile. C. difficile causes diarrhea and colitis by releasing two high molecular weight protein exotoxins, toxin A and toxin B, with potent cytotoxic and enterotoxic properties. Evidence presented here indicates that C. difficile toxins compromise the epithelial cell barrier by at least two pathophysiologic pathways, one involving disaggregation of actin microfilaments in colonocytes via glucosylation of the Rho family of proteins leading to epithelial cell destruction and opening of the tight junctions, whereas the other appears to involve early release of proinflammatory cytokines from intestinal epithelial cells probably via activation of MAP kinases. We speculate that cytokines released from intestinal epithelial cells in response to toxin A exposure will diffuse into the lamina propria and activate macrophages, enteric nerves, and sensory neurons to release SP, CGRP, and NT, which, in turn, interact with immune and inflammatory cells and amplify the inflammatory response. Dissection of this inflammatory cascade may help us understand the pathophysiology of inflammatory diarrhea caused by this important pathogen. PMID- 11193599 TI - Ion transport during growth and differentiation. AB - The major function of the adult colon is to reabsorb fluid from the chyme. This ability to conserve salt and water is especially important in newborns, where reserves are small and diarrhea is frequent. Although much is known about regulation of Cl- transport in the adult colon, postnatal changes in electrolyte transport are not well characterized. We have established an in vitro model to study colonic epithelial cells (colonocytes) at different stages of development. Primary cultures were isolated from newborn, weanling, and adult rabbit colon and properties such as growth and Cl- transport characterized. The isolation procedure yielded a crypt-enriched population of cells, and the cell yield per gram mucosa increased with age. The colonocytes also showed an age-related decrease in attachment to extracellular matrix, with maximum attachment seen with Matrigel and collagen IV. The crypt enrichment was confirmed by demonstrating that the cell population was capable of transporting Cl-, which was stimulated by agents such as forskolin and phorbol esters at all ages. Agents that increased intracellular cGMP, however, did not increase Cl- transport at any age. It was interesting to observe that the secondary bile acid, taurodeoxycholate, stimulated Cl- transport only in the adult but not newborn or weanling distal colonocytes. We have demonstrated that rabbit distal colonocytes can be kept viable in culture and transport Cl- at all ages. However, the regulation of Cl- transport changes during ontogeny and depends on the signaling pathway. PMID- 11193600 TI - Cl-dependent Na-H exchange. A novel colonic crypt transport mechanism. AB - This communication summaries a series of observations of the transport function of the crypt of the rat distal colon. Development of methods to study both 22Na uptake by apical membrane vesicles prepared from crypt cells and intracellular pHi (pHi), fluid movement (Jv), and bicarbonate secretion during microperfusion of the crypt has led to the identification of (1) a novel Cl-dependent Na-H exchange (Cl-NHE) that most likely represents the coupling of a Cl channel to a Na-H exchange isoform that has not as yet been identified and (2) bicarbonate secretion that appears to be most consistent with HCO3 uptake across the basolateral membrane by a mechanism that is closely linked to Cl transport and its movement across the apical membrane via an anion channel. Na-dependent fluid absorption is the constitutive transport process in the crypt, while fluid secretion is regulated by one or more neurohumoral agonists. Cl-NHE is responsible for both the recovery/regulation of pHi in crypt cells to an acid load and fluid absorption. PMID- 11193601 TI - Coupling between Na+, sugar, and water transport across the intestine. AB - Water is absorbed across the small intestine in the absence of external driving forces. However, it has been established that water transport is secondary to active sodium transport. In the upper intestine both sodium and water absorption are largely dependent on the presence of D-glucose. The link between active sodium transport and glucose is the coupled transport of sodium and glucose across the brush border membrane of enterocytes by the Na+/glucose cotransporter (SGLT1). Na+ that enters the cells with glucose is pumped out towards the blood by 3Na+/2K+ pumps on the basolateral membrane, and glucose passes out across the basolateral membrane by facilitated diffusion, the net result being that glucose and sodium are transported across the epithelium. The coupling between Na+, glucose, and water transport is less well understood. It is commonly thought that Na+ transport increases the local osmotic pressure in the lateral intercellular spaces, and that this in turn generates osmotic water flow across the epithelium. Recent work suggests a more direct link between Na+, glucose, and water transport; that is, water is cotransported along with Na+ and sugar through SGLT1. Here we review the evidence for Na+/glucose/water cotransport. PMID- 11193602 TI - Regulation of chloride secretion. Novel pathways and messengers. AB - The capacity for active chloride secretion, thereby driving the secretion of fluid, is an important property of the intestinal epithelium. Chloride secretion is stimulated by mechanisms involving increases in either cyclic nucleotide or cytoplasmic calcium concentrations. The calcium-dependent response is transient and limited in its magnitude, implying that negative signaling events may restrict the overall extent of this mode of chloride transport. We have uncovered a number of negative signaling mechanisms intrinsic to the epithelium that uncouple increases in calcium from the downstream response of chloride secretion. These involve various kinase cascades, the generation of messengers derived from membrane phospholipids, and interactions of G protein-coupled receptors with those for peptide growth factors such as epidermal growth factor. This chapter will review emerging information on the details of these negative signaling mechanisms, as well as points of convergence and divergence. The possible physiological and pathophysiological significance of such signaling will also be discussed. PMID- 11193603 TI - Neurotransmitters in neuronal reflexes regulating intestinal secretion. AB - The intestinal crypt cell secretes chloride into the lumen, resulting in accumulation of fluid that normally thins out mucus or, at higher secretory rates, flushes out the contents. The regulation of chloride secretion occurs by neural reflex pathways within the enteric nervous system. Mechanical stimulation releases 5-hydroxytryptamine (5-HT) from enterochromaffin cells with subsequent activation of intrinsic primary afferents that carry electrical signals to submucosal ganglia. After processing, interneurons activate cholinergic and vasoactive intestinal peptide (VIP) secretomotor neurons. Acetylcholine and VIP bind to epithelial receptors and stimulate sodium chloride and fluid secretion. Reflex-evoked secretory rates can be modulated by a variety of mediators at the level of the enterochromaffin cells, neurons within the reflex pathway, or epithelial cells. Understanding the complex regulatory mechanisms for chloride secretion is likely to provide mechanistic insights into constipation and diarrhea. PMID- 11193604 TI - Three 5'-variant mRNAs of anion exchanger AE2 in stomach and intestine of mouse, rabbit, and rat. AB - AE2 is one of three known isoforms of the anion exchanger (AE) gene family. The use of alternative promoters, resulting in a tissue-specific transcript pattern, was reported for all AE genes. Three N-terminal variant AE2 subtypes are described: AE2a, AE2b, and AE2c. Although the basolaterally located parietal cell anion exchanger is known to be an AE2, the molecular identity of the basolateral and apical anion exchangers throughout the gut are still unknown. This article summarizes functional, immunohistochemical, and Western blot data demonstrating the basolateral localization of the gastric and intestinal AE2 in rabbit, mouse, and rat, and showing the AE2 subtype mRNA expression pattern in the stomach and along the intestine of rabbit and mouse: AE2a is expressed in all studied tissues, but most strongly in the colon; AE2b is expressed mainly in the stomach; and AE2c is detected nearly exclusively in the stomach. Further investigation is necessary to characterize the apical anion transport protein involved in NaCl absorption and HCO3- secretion in the gut. PMID- 11193605 TI - Differential regulation of ENaC by aldosterone in rat early and late distal colon. PMID- 11193606 TI - Epithelial phosphate transporters in small ruminants. PMID- 11193607 TI - Inflammatory mediators influencing submucosal secretory reflexes. PMID- 11193608 TI - The role of the OIE in international trade. AB - The OIE (Office International des Epizooties), the world animal health organization, has been addressing the most serious animal diseases throughout the globe for the past 75 years. It has developed guidelines for safe international trade in animals and animal products as part of its original mandate. Since the establishment of the World Trade Organization and the Sanitary and Phytosanitary Agreement, the role for the OIE has changed. At this point in the history of the OIE, new demands, expectations and challenges lie ahead as the OIE faces a new role in international trade. PMID- 11193610 TI - A Swedish/European view of bioterrorism. AB - Bioterrorism includes possible use of Weapons of Mass Destruction (WMD), preferably biological agents, by non-state terrorist groups as well as criminal clusters. The threat from terrorists to utilize biological agents to achieve goals is not new, but the threshold to realize the threats seems to be lower than previously expected. It can be argued that as targets for bioterrorism Sweden and Europe are less likely than is the U.S. However, with the collapse of the former Soviet Union heavy mafia-based groups have emerged in Russia with the intent to obtain and trade material and utilities for the creation of WMD. Such activities are reaching far beyond the borders and can thus be found in Sweden as well as the other countries of Europe. This together with the fact that groups of different shades of political opinion can come in open conflict in the most unexpected countries of Europe have given bioterrorism a face in Sweden, as well as in the rest of Europe. PMID- 11193609 TI - Cryptosporidiosis. A global challenge. AB - During the last 30 years, our concept of cryptosporidiosis has changed from that of a rare, largely asymptomatic disease, to an important cause of diarrhea in animals and humans worldwide. Significant disease first appeared in cattle. Subsequently, the zoonotic danger of the organism was recognized in HIV-infected persons and young children. Cryptosporidium are now ubiquitous and disease has been described in over 79 host species. Cryptosporidiosis has become a major cause of calfhood diarrhea worldwide. In humans it accounts for up to 20% of all cases of childhood diarrhea in developing countries and is a potentially fatal complication of AIDS. Waterborne contamination is a growing concern as a source of widespread outbreaks of disease. Factors that have contributed to the emergence of cryptosporidiosis in animals include biological features of the organism, the lack of an effective treatment or preventative, increased environmental contamination, and trends in livestock production. In humans the zoonotic nature of infection and an increased at-risk population have contributed to disease. Genetic characterization of Cryptosporidium, improved detection methods, and a better understanding of the factors that predispose to disease are important contributions to understanding the epidemiology of cryptosporidiosis. PMID- 11193611 TI - Response to bio-terrorism directed against animals. AB - The Animal and Plant Health Inspection Service (APHIS) has a long history of rapid direction, control, and eradication of devastating diseases. Our immediate response mechanisms to diseases such as avian influenza, Venezuelan equine encephalomyelitis, and Newcastle disease, have long been recognized by the global emergency response community as models of control and eradication. APHIS and the U.S. livestock industries, in partnership with the Animal Agriculture Coalition, re-evaluated the Nation's animal health emergency preparedness and response systems. The group identified areas that negatively impact, biologically and/or economically, the Nation's animal and food production industries. To counter the increased risks including bioterrorism, APHIS plans to establish a world-class "Center of Excellence for Animal Health Emergency Management." APHIS, Intelligence agencies, other Federal departments, State governments, and industries are working together to provide accurate information on the foreign and domestic threats posed to the U.S. agricultural sector by biological weapons. Additionally, the same agencies and organizations are evaluating, updating, and improving the coordination and training mechanisms necessary to respond in the even of a widespread pest or disease outbreak. PMID- 11193612 TI - Mitigation of bioterrorist threats in the 21st century. AB - There is a raising level of awareness and concern that agriculture and food supplies might serve as targets for bioterrorists. To minimize such threats a number of new initiates are urgently needed: 1. Greater levels of financial commitment from federal, state, and international organizations for research on highly infectious diseases and for emergency response infrastructure; 2. Wellorchestrated emergency response plans based on inter-agency, inter departmental and stakeholder working groups; 3. Teams prepared for risk assessment and risk communication; 4. Modern systems of animal identification and accurate trace-back for animal movement; 5. Increased biosecurity in intensive production operations; 6. Accurate intelligence as to what pathogens pose the highest risks for economic and social impact; 7. Establishment of new international animal and plant disease research networks and partnerships; 8. Strengthen international disease surveillance networks for early detection and intervention; 9. New generations of rapid diagnostic tests for pathogen detection that are practical for field and diagnostic laboratories; 10. Increased level of commitment to pathogen genomics research for molecular epidemiology and vaccine development; 11. New chemical and immunological intervention strategies to prevent or control disease outbreaks; 12. Increased level of training on exotic and emerging animal diseases in basic veterinary education and through continuing education for veterinarians, state and federal field personnel and laboratory diagnosticians. PMID- 11193613 TI - The role of diagnostic laboratories in disease control. AB - Recognition of disease is the foundation of disease control and prevention. In the process of disease recognition, the diagnostic laboratory forms the third (and last level) following the animal owner and the practitioner. The diagnostician's main role is determination of disease etiology. Secondary but equally important roles played by the diagnostic laboratory include: 1) consultative/advisory role; 2) interpretative role; and 3) disease surveillance role. This presentation will discuss these various roles and the interactions of the diagnostic laboratory with other players in the process of disease recognition. PMID- 11193614 TI - The role of the World Reference Laboratories for Foot-and-Mouth Disease and for Rinderpest. AB - The World Reference Laboratories for Foot-and-Mouth Disease and for Rinderpest provide a worldwide diagnostic and surveillance service for these disease for FAO and OIE. Both laboratories are housed within the high security facility of the Institute for Animal Health, Pirbright, UK. Foot-and-mouth disease (FMD) and rinderpest (RP) are OIE List A diseases and historically have caused huge losses to agricultural economies around the world, prompting the establishment of veterinary colleges in Europe and environmentally controversial control programs in Africa. FMD and RP have now been geographically restricted, but the large legal and illegal world trade in live animals and animal products constantly threatens to allow them to spread back into disease-free areas. The Reference Laboratories provide a center of excellence for the development of improved diagnostic techniques and a repository of isolates collected over many years. These libraries provide material for investigations of the molecular epidemiology and evolution of the viruses and a data base against which new isolates can be compared. Thus it is possible to individually characterize new outbreak strains, identify their likely origin and provide the most up-to-date support for their control. PMID- 11193615 TI - Development, testing and commercialization of a new brucellosis vaccine for cattle. AB - Vaccines used against brucellosis do not generally protect completely against infection or abortion. Genetic analysis has revealed differences in arrangements of DNA sequences between these vaccine strains and the virulent parent strain and permits the specific identification of field isolates of B. abortus as wild-type or vaccine strain. B. abortus strain 19 is a low-virulence, live vaccine developed for use in cattle. Although it is effective, strain 19 vaccine had a tropism for the placenta and caused abortion when given to pregnant cows, was infectious for humans, and caused serologic responses in calves that could not be differentiated from those in cattle infected with natural field strains. In the mid-1980s the need for a new vaccine emerged when the USDA increased its efforts in brucellosis eradication. In the 1990s, research on biosafety, vaccine efficacy and field application rapidly established the fact that strain RB51 is protective in cattle at doses comparable to those of strain 19. Thus, Brucella abortus strain RB51 is the vaccine of choice against brucellosis of cattle in the United States. Studies have established the relative efficacy of strain RB51 vaccine on bison, and the vaccine has also been accepted for use in commercial bison herds in the U.S. PMID- 11193616 TI - Culture-derived parasites in vaccination of cattle against tick-borne diseases. AB - The major economically important tick-borne diseases of cattle are theileriosis, babesiosis, anaplasmosis, and cowdriosis. Culture-derived attenuated schizonts of Theileria annulata have proved to be safe for all types of cattle and they protect against tick-borne theileriosis. T. parva was also successfully grown in vitro; however, inoculation of cattle with allogeneic schizont-infected cells resulted in rejection and destruction of the parasites together with the host cells. The number of schizont-infected cells needed for immunization is greater than for T. annulata theileriosis. Culture-propagated Babesia bovis and B. bigemina were used for large scale vaccination in the field. An avirulent population of Babesia spp. was obtained by in vitro cloning; inoculation of cattle did not induce clinical babesiosis, but produced specific antibodies. Culture-derived exoantigens of Babesia spp. proved to be completely safe for cattle, however, they conferred less protection than live parasites. Cell cultured Cowdria ruminantium was highly infective for susceptible animals but, attenuated in vitro, could offer a potential source for vaccination. Anaplasma marginale, successfully grown in tick cell culture, may be developed for vaccines. Factors that should be considered in the developing of vaccines against tick-borne diseases include: the protective immune response to the pathogenic parasite developmental stages, virulence, immunological strain differences, and antigenic variations in cattle and in culture. PMID- 11193617 TI - Biocontrol of ticks. AB - The increasing resistance of arthropodes to pesticides, their high price, and the growing public demand for safer food and a cleaner environment are obliging animal growers to minimize the use of pesticides by introducing alternative means for tick control. The development of a biological tick control method has been neglected as compared to the control of plant pests or dipterous insects harmful to men and animals. There are abundant observations, but only a few studies have as yet been conducted on pathogens, parasitoides, and predators of ticks. A first attempt at tick biocontrol was made with the introduction of tick-parasitic wasps from France to the USA and Russia. During the past decade, interest in developing antitick biocontrol agents such as birds (Brazil, Kenya, and Zimbabwe), parasitoides (Kenya and USA), entomopathogenic nematodes (Egypt, Israel, Guadeloupe, and USA), entomopathogenic fungi (Brazil, Cuba, Israel, Kenya, and USA), and bacteria (Brazil) has gained momentum. The reintroduction of oxpecker birds in some areas of Zimbabwe remains up to now the only known successful attempt at tick biocontrol. PMID- 11193618 TI - Eradication and surveillance of the tropical bont tick in the Caribbean. An international approach. AB - The Caribbean Amblyomma program (CAP) is a multidonor funded effort involving several technical organizations and national governments in the eradication of the tropical bont tick. The Food and Agriculture Organization (FAO) is the lead technical agency, providing both technical and administrative support to the CAP Regional Coordination Unit (RCU) based in Barbados. All collaborating agencies, donors, and national representatives are members of the Amblyomma Program Council (APC), the overall governing body of the CAP. In addition to FAO, the other organizations involved are the Caribbean Community (CARICOM), the European Union (EU), the Inter-American Institute for Cooperation on Agriculture (IICA), the International Fund for Agricultural Development (IFAD), and the United States Department of Agriculture (USDA). Several agencies (EU, FAO, IFAD, and USDA) are also major donors. The CAP cooperates with the complementary Plan POSEIDOM Veterinaire Program in the French West Indies. The University of the West Indies (UWI), the International Institute for Biological Control (IIBC), and the Departement d'Elevage et de Medecine Veterinaire des Pays Tropicaux (EM-VT) in Guadeloupe are other collaborators. PMID- 11193619 TI - World Trade, disease and Florida's animal populations. The changing dynamics. AB - One of Florida's three leading economic industries is agriculture. Agriculture feeds and enhances the lives of millions of people in Florida, the United States, and the entire world. Agriculture in Florida results in more than $6 billion in farm cash receipts, employment for more than 60,000 people a month, more than $18 billion in farm-related economic activity and stretches from the farm gate to the state's supermarkets with an impact of nearly $45 billion. The domestic and wild animal populations of Florida, our unique relationship to the Caribbean, Atlantic Ocean, Gulf of Mexico, Central and South America, as well as tourism, diverse human population growth and immigration, all add to the complexity of an environment capable of establishing many animals, animal pests and diseases not native to the United States. Never before have the dynamics of disease control involved as much challenge and diversity. Is the balance at risk, or is the risk over-balanced? Can science, economics and politics blend to maintain this balance? How will the balance affect world trade, disease control and the animal populations of Florida? PMID- 11193620 TI - Screwworm eradication in the Americas. AB - The screwworm fly, Cochliomyia hominivorax (Coquerel), is a parasite that attacks all warm-blooded animals including humans. This parasite has caused significant losses to the livestock industries of the Americas. Since the screwworm eradication program was initiated in the Southeastern United States in 1957, the eradication program has successfully progressed to its current location in Panama. A variety of technologies and tools have been used in the eradication programs. The cooperative agreement has been a significant tool in the success of the program. In the United States, the State-Federal Cooperative programs provided the mechanism for carrying out screwworm eradication. Once screwworms were eradicated from the United States, the need to expand the program internationally, in order to protect the United States, became evident. A cooperative agreement created the Mexico-United States Commission for the Eradication of Screwworms (Commission). Commission-Guatemala and Commission Belize Cooperative Agreements were used to eradicate screwworms from these countries. Followup programs in El Salvador, Honduras, Nicaragua, Costa Rica, and Panama were implemented by cooperative agreements between the United States Department of Agriculture and the individual countries. The positive and negative aspects, as well as the necessary elements of successful cooperative agreements, are discussed. PMID- 11193621 TI - International approach to eradication and surveillance for foot-and-mouth disease in the Americas. AB - Foot-and-mouth disease (FMD) was introduced into the Americas in 1870. At that time the disease was described simultaneously in the North coast of the United States of North America, the Province of Buenos Aires in Argentina, the central region of Chile, Uruguay, and South Brazil. At the beginning of the twentieth century the disease spread to the rest of Brazil, Bolivia, Paraguay, and Peru. In 1950 the disease was introduced into Venezuela, and in the same year to Colombia, and from there to Ecuador. The United States of America eradicated an outbreak of FMD in 1929. Outbreaks of FMD were also eradicated from Mexico in 1947 and from Canada in 1952. The last outbreak that occurred in Mexico in 1954 was also eradicated. In 1951 the Americas Animal Health Authorities decided to establish a Pan-American Foot-and-Mouth Disease Center (PANAFTOSA), initially as a special program within the American States Organization (OAS). The center was later transferred to the Pan-American Health Organization (PAHO). In the early 1970s PANAFTOSA developed a proposal for a continental surveillance system for vesicular diseases, which was approved by Agriculture Ministers at an International Meeting for FMD and Zoonoses (RICAZ). Since then, PANAFTOSA dedicated all efforts to collaborate with each country in the implementation of the system and to receive, analyze, and distribute a weekly report of vesicular diseases. The model was elaborated using coordinate grid maps, one for the South American Continent, others for each country in the region. The reports from each country consist of the grid location for any suspicious outbreak of vesicular disease. Using the information gathered during visits to the countries, as well as weekly reports, and by studying the most frequent animal movements within the region, PANAFTOSA developed a proposal for FMD eradication. This plan was approved by the Government of South America and implemented in cooperation with PANAFTOSA. The hemispheric plan for FMD eradication (PHEFA), has been implemented and today Chile and Uruguay are FMD free without vaccination; Argentina, Paraguay, and the states of Rio Grande do Sul and Santa Catarina in Brazil are also recognized by the OIE to be FMD Free, with vaccination. The use of the continental surveillance system is the main strategy for achieving the eradication of FMD in South America. At this time PANAFTOSA is working to improve the system, and to add other diseases indicated by the governments of the Americas. PMID- 11193622 TI - Animal trypanosomiasis in South America. Current status, partnership, and information technology. AB - Animal trypanosome species of economical importance in South America include T. vivax and T. evansi. Both species are described in Brazil, Bolivia, Colombia, French Guyana, Peru, Suriname, and Venezuela. In Argentina and Guyana, only T. evansi and T. vivax are found, respectively. Our studies on T. vivax indicated that the parasite was spreading around 1.3 km per day in Bolivia. We found severe leukopenia in bovines from Pantanal (Brazil) and the Department of Santa Cruz (Bolivia). Because it can cause immunosuppression, the importance of trypanosomiasis control in ensuring success of vaccination campaigns against foot and mouth disease (FMD) in the Pantanal and Bolivia should be considered. The use of one needle for several animals during FMD campaigns in Brazil and Bolivia could also contribute to the spread of T. vivax. The anticipated losses due to T. vivax could exceed $160 million, assuming there are 11 million head of cattle in the Brazilian Pantanal and Bolivian lowlands. International collaboration among research institutes is needed to deal with these diseases and parasites. Previous efforts using information technologies resulted in the creation of two discussion lists (Tryplink and Trypan), the edition of the on-line version of Trypnews and Internet conferences. PMID- 11193623 TI - An international approach to laboratory diagnosis of animal diseases. AB - During the past thirteen years, and as part of an overall support program for developing countries, the Joint FAO/IAEA Division has developed a series of standardized and internationally validated ELISA-based systems for the diagnosis and surveillance of the major epizootics affecting livestock in the developing world. Linked to comprehensive internal and external quality assurance protocols and to the use of standardized equipment and data management software, veterinary laboratories in many developing countries are now able to provide quality assured results on the prevalence of the major diseases affecting their livestock. This internationally standardized approach can rapidly enable developing countries to both monitor the effectiveness of their disease control and eradication programs and to meet requirements for international disease status recognition and for trade in livestock and livestock products. PMID- 11193624 TI - Assessing infestation risk by vectors. Spatial and temporal distribution of African ticks at the scale of a landscape. AB - Control of major livestock diseases in the tropics, such as theileriosis or trypanosomosis, is still largely based on the control of their vectors. Understanding the distribution of vectors, such as ticks and tsetse flies, is needed in order to improve the efficiency and economical viability of control operations. Technical improvements such as remote sensing and global information systems have allowed valuable improvements for the prediction of large-scale vector distribution (continental to national), but trying to make these predictions at the scale of a landscape is facing other challenges. At this scale, an analysis of host/vector interactions with an evolutionary point of view is useful. A study was undertaken on a mixed game/cattle ranch in Zimbabwe during which we monitored variations in the abundance and spatial distribution of the immature free stages of Rhipicephalus appendiculatus/R. zambeziensis and R. e. evertsi, two major groups of tick species in Southern Africa. We found two contrasting distributions in relation to contact between tick larvae. The ungulate-host R. e. evertsi appeared to be unpredictable, whereas R. appendiculatus/R. zambeziensis were predictable in time and space, but associated with key-resources for ungulates (water and forage resources). The consequences of such distributions are discussed in terms of vector control. PMID- 11193625 TI - An in vivo model to investigate lymphocyte-mediated immunity during acute hemoparasitic infections. Use of a monoclonal antibody to selectively deplete CD4+ T lymphocytes from thymectomized calves. AB - Thymectomized calves were selectively depleted of CD4+ T lymphocytes with a monoclonal antibody (mAb) specific for the bovine CD4 monomer (ILA-11). Calves were treated with high loading doses of ILA-11 during the first week of the study then treated with subsequent lower maintenance doses. Depletion of CD4+ T lymphocytes was assessed weekly by flow cytometric analysis of PBMC and mononuclear cells from lymph node and spleen biopsies. Treatment with high doses of ILA-11 resulted in rapid and marked depletion of CD4+ T lymphocytes from the peripheral blood, peripheral lymph nodes, and spleen. Although CD4+ T lymphocytes slowly returned to the peripheral blood, peripheral lymph nodes, and spleen by day 21 post-treatment, the numbers of CD4+ T lymphocytes in depleted calves remained below pre-depletion levels for the duration of the study. CD4+ T lymphocytes failed to be effectively depleted from a non-thymectomized calf treated with the mAb ILA-11. Development of a T lymphocyte depletion model in thymectomized calves will permit testing of the hypothesis that CD4+ T lymphocytes and IFN-gamma are required in cattle for control of acute anaplasmosis. In subsequent planned studies, thymectomized calves depleted of CD4+ T lymphocytes will be experimentally infected with A. marginale and parameters of disease compared between depleted and non-depleted calves. PMID- 11193626 TI - Challenges of non-tsetse transmitted animal trypanosomoses (NTTAT). An outline and some perspectives. AB - Non-tsetse transmitted animal Trypanosomoses (NTTAT) result from infection by Trypanosoma evansi, T. equiprdum, and T. vivax. The latter is present both in South America and in tsetse depopulated areas of Africa. Since the inception of the OIE group, numerous studies have been carried out to result in a better understanding of this infection and hope for immunological control. PMID- 11193627 TI - Protecting health, facilitating trade, or both? AB - The General Agreement on Tariffs and Trade (GATT) has existed and dealt with trade issues since 1947. However, to take on the question of to what extent can we set fair and science-based rules allowing countries to have the sovereign right to set measures for protecting public, animal and plant health and food safety, while not creating unjustified barriers to trade was the challenge of the Uruguay Round negotiators. The outcome of this seven-year exercise was the SPS Agreement discussed here. A number of key issues are addressed: transparency including notification, special and differential treatment for developing countries, harmonization, equivalence, regionalization, risk analysis, and other matters. Early warning and exposure of these issues has encouraged countries to resolve their problems quickly. Some of the issues that should be taken into consideration during this next round are the following: biotechnology, aquaculture, consumer concerns, animal welfare, the environment, organic foods, morality in trade, compliance with the WTO, compensation, and the precautionary principle. Compliance with the decision of the WTO is an area of grave concern, especially if developed and powerful countries continue to threaten the survival of the WTO system through lengthy and costly legal interpretations and appeals of dispute settlements without serious efforts by all parties to find win-win solutions. In spite of these problems, over all we must recognize the significant gains in trade thanks to the SPS Agreement. The most flagrant trade violations have been eliminated as a result of improved transparency in the process. Consumers are in general better off, since they have greater diversity and increased safety in what they can buy. PMID- 11193628 TI - Rapid recovery and identification of anthrax bacteria from the environment. AB - Bacillus anthracis has been recognized as a highly likely biological warfare or terrorist agent. We have designed culture techniques to rapidly isolate and identify "live" anthrax from suspected environmental release. A special medium (3AT medium) allows for discrimination between closely related bacilli and non pathogenic strains. Nitrate was found to be a primary factor influencing spore formation in Bacillus anthracis. Nitrate reduction in anthrax is not an adaptation to saprophytic environmental existence, but it is a signal to enhance environmental survival upon the death of the anthrax host, which can be mimicked in culture. PMID- 11193629 TI - Future perspectives on veterinary hemoparasite research in the tropics at the start of this century. AB - This paper has two main objectives: (1) to promote discussion about the future of veterinary hemoparasite research at the start of the twenty-first century and the third millennium, and (2) to stimulate young students to start research on parasitology, in particular in the field of veterinary tropical diseases. It is well known that in the twenty-first century human society will be challenged by several major problems resulting from the demographic explosion, since the Earth's population for the year 2020 will reach 8.5 billion, or 10 billion for the year 2050, as long as the birth rate decreases from 2.8 births per woman today to 2.0 by the year 2030 (data released by the U.N. Population Fund, 1998). Since the food production rate, either from plant or animal origin, is lower than the human birth rate, the challenge ahead will be to produce enough food for ten billion people. Consequently, to deal with this problem, especially in developing nations, it is proposed: (1) to give priority status to scientific research in the agriculture and animal fields; (2) to concentrate financial support and efforts for research especially on hemoparasitic diseases (i.e., babesiosis, anaplasmosis, cowdriosis, ehrlichiosis, and trypanosomosis), in particular to apply biotechnology techniques to those animal diseases; and (3) to grant a better role to studies on veterinary and medical parasitology in universities of the Americas and Europe, since in these universities parasitology is currently considered a secondary subject. PMID- 11193630 TI - Ethnoveterinary medicine and indigenous pharmacopoeia of Passore Province in Burkina Faso. AB - A study of traditional animal health care practices in Passore province of Burkina Faso led to the characterization of 24 diseases, together with their local names, causes of their appearance, and their treatment. Most (95%) of the medicinal recipes used to treat affected animals were based on plants. PMID- 11193631 TI - The epidemiology of Theileria parva infections on smallholder dairy farms in Kenya. AB - The purpose of the study was to characterize the differences in epidemiology (risks of infection, morbidity, mortality) and potential control of East Coast fever (ECF) between the selected strata. Evidence of Theileria parva infection was assessed by increased antibody levels as measured in an indirect ELISA test by the percent positivity (PP) of serum samples relative to a strong positive reference serum. A prospective cohort study was conducted in five purposively sampled agroecological zone (AEZ)-grazing system strata in Murang'a District, Kenya, between March 1995 and June 1996. The study strata were selected to represent the widest range of ECF risks in the district and included, zero grazing and open-grazing farms in the Upper Midlands (UM) one and four AEZs and zero-grazing farms in the UM2 AEZ. In total, 225 calves from 188 smallholder farms were examined from birth to age six months. Calves were recruited into the study at birth and visited within the first two weeks of life and thereafter at biweekly intervals for up to 14 visits. Important differences were observed between the different AEZ-grazing strata. Seroconversion risks of T. parva were highest in the UM4-open grazing stratum. Antibody prevalence in adult cattle and ECF morbidity and mortality risks were also highest in this stratum. In the open grazing strata, particularly in the lower elevation AEZ, UM4, there was stronger challenge and a greater impact of ECF. There is likely to be an expansion of smallholder dairy farming into this area so that it is likely to be the most important target production system for ECF control in the central highlands of Kenya. PMID- 11193632 TI - Phylogenetic analysis by rRNA comparison of the highly pathogenic sheep-infecting parasites Theileria lestoquardi and a Theileria species identified in China. AB - In the Northwestern part of China there have been reports of clinical cases in small ruminants of a haemoparasite with the characteristics of Theileria hirci (T. lestoquardi). However, some properties of this parasites argue against its classification as T. lestoquardi. In this paper, we present evidence that T. lestoquardi and the Chinese Theileria isolate are distinct parasite species. Phylogenetic analysis of determined nucleotide sequences of small subunit ribosomal RNA (srRNA) genes of T. lestoquardi and the Chinese Theileria parasite show that they belong to different clades within the phylogenetic tree of piroplasms. The srRNA sequence of the Chinese parasite was found to be most closely related to T. buffeli, which, with T. sergenti, belongs to an evolutionary lineage of non-lymphoproliferative Theileria species. On the other hand, it was clearly divergent to a lineage of lymphoproliferative Theileria species; T. annulata, T. parva, T. taurotragi, and T. lestoquardi, the latter being most closely related to T. annulata. PMID- 11193633 TI - Lymphocyte stimulatory capacity of Theileria annulata-infected ovine lymphoblastoid cells. AB - T. annulata, the causative agent of tropical theileriosis in cattle, is transmitted by ticks of the genus Hyalomma. Sporozoites of this parasite invade their target cells, where they differentiate to macroschizonts. T. annulata additionally invades and transforms ovine and caprine leukocytes. T. annulata infection in the ovine system is poorly studied, thus we used a mixed lymphocyte culture (MLC) to analyze the capacity of these cells to activate naive uninfected ovine cells. The peak response was observed on day three or four and the response could not be induced by lysates of infected cells or their supernatants. The stimulated cells expressed IL-2 and secreted an IL-2-like growth factor. PMID- 11193634 TI - Humoral immune response of dogs immunized with salivary gland, midgut, or repeated infestations with Rhipicephalus sanguineus. AB - The antibody (Ab) responses of dogs immunized with adult tick salivary gland (TSG), midgut (TMG), or repeated infestations of Rhipicephalus sanguineus were monitored to determine if there is an association between Ab production and R. sanguineus performance. Tick-naive dogs were immunized with TSG or TMG and subjected to two challenge infestations. The control group was infested five times at 21-day intervals. The ELISA technique was used to measure Ab levels in sera from these dogs, which expressed different forms of resistance against R. sanguineus. In dogs immunized with TSG or TMG, similar Ab levels were detected against TMG, TSG, muscle, synganglion, and reproductive organs. However, these sera had different Ab levels against egg mass, unfed larvae, fed larvae, and nymph antigens. Ab levels to muscle, nerve, and reproductive antigens were lower than those observed when TMG or TSG antigens were used. Sera from dogs immunized with TMG or TSG responded to most tick stages or tissue antigens, whereas repeated infestation sera showed the lowest response among the three groups. PMID- 11193635 TI - Ticks associated with wild animals in the Nhecolandia Pantanal, Brazil. AB - A study of ticks associated with wild animals was carried out from September 1996 to April 1998 at the Fazenda Alegria (21,000 ha), in the Nhecolandia Pantanal, State of Mato Grosso do Sul, Brazil, a sunken plain bordering the upper Paraguay river, located 19 x 08'S; 56 x 46'W. A total of 81 wild animals (13 species, 6 orders) were captured with the aid of nets, and ticks were found on 63 (78%). Tick species identified included Boophilus microplus (Canestrini), Amblyomma cajennense (F.), A. parvum (Aragao), A pseudoconcolor (Aragao), A. scalpturatum (Neumann), A. nodosum (Neumann), A. ovale (Koch), and A. tigrinum (Koch). Dragging from grasslands (campos) yielded negative results compared to the high concentration of ticks, mainly nymphs, that were collected from leaves in the forests (capao). Predominance of immature instars (Amblyomma genera) was observed in the end of winter (August-September). Ticks were associated mainly with coatis, deer (Mazama gouazoubira) and anteater, and these animals may play a role in the epidemiology of tick-transmitted pathogens in the Pantanal if one considers their co-existence with local domestic animals. PMID- 11193636 TI - Thermal constant estimation in tropical horse tick, Anocentor nitens (Acari:Ixodidae). AB - Experience has demonstrated that the exclusive use of acaricides as a control method against cattle ticks causes several problems, and is not totally effective. Other methods need to be added in order to achieve better and more profitable control of these parasites. Groups of 12 to 15 engorged ticks, bred on bovines, were individually incubated at six temperatures (T = 24, 26, 28, 30, 32, and 34 degrees C) and four relatives humidities (RH = 100, 80, 75.5, and 70%), creating 24 variants. The onset of oviposition and eclosion (emergence of larvae from eggs) was observed in all ticks, and preeclosion times (PET) were determined. A linear regression equation for the velocity of development with temperature as a function of the inverse of PET was calculated for each RH value. For each RH the minimum thermal threshold (MTT) was obtained by extrapolation and the effective temperature summation (ETS) calculated from the equation (incubation temperature--MTT) x PET. The four MTT values obtained were not significantly different; the mean value of MTT was 15.25 degrees C. The thermal constants did not prove to be not statistically different over the range of RH values employed in the experiments, the mean being 354.04 degrees C-day. PMID- 11193637 TI - Laboratory evaluation of pathogenicity of entomogenous nematodes to African tick species. AB - Five strains of entomogenous nematodes, Steinernema carpocapsae strains DD, Mexican, SR, and Heterorhabditis bacteriophora strains 1S5 and HP88, were tested for their pathogenicity to various developmental stages of five African tick species namely; Rhipicephalus appendiculatus, R. evertsi, Amblyomma variegatum, A. gemma, and Boophilus decoloratus. In engorged female R. appendiculatus, all nematodes at a concentration of 1,000 infective juveniles (IJ)/dish, except S. carpocapsae Mexican strain, induced high mortalities (56-100%), whereas in engorged female R. evertsi, only S. carpocapsae DD and H. bacteriophora HP88 induced high mortalities (78% and 56%, respectively). In engorged B. decoloratus, S. carpocapsae DD, Mexican, SR and H. bacteriophora HP88 (100 IJ/dish) induced mortalities of 85%, 65%, 80%, and 100%, respectively. In all cases, except for S. carpocapsae Mexican strain, a higher concentration (5,000 IJ/dish) did not result in higher mortality than occurred with 1,000 IJ/dish. Unfed females and immature stages of ticks were found to be generally resistant to the nematodes. The feasibility of using entomogenous nematodes for biological control of African tick species are briefly discussed. PMID- 11193640 TI - Artificial feeding in Boophilus microplus (Acari:Ixodidae) through micropipettes. AB - Newly molted Boophilus microplus females obtained in a laboratory at 30 degrees C and environmental relative humidity (RH) were employed. An original device was used to hold ticks during feeding. Three groups of 15 ticks each were created: unfed, fed with heparinized blood, and fed with defibrinated blood. Ticks were weighed before and after feeding. Females were restricted by group in three isolators attached on the skin of a bovine. Ten sexually competent males were added to each isolator. Time of coupling, tick mortality, time of detachment, and weight of engorged ticks were determined. Engorged females were incubated at 30 degrees C and 100% RH. Periods of nonparasitic phase, laying efficiency, and fertility of eggs were noted. There were no statistical differences between the three groups. This means that feeding with micropipettes does not affect the non parasitic phase of B. microplus, the differences between heparinized and defibrinated blood are not significant. PMID- 11193638 TI - Larval survival of Anocentor nitens under simulated natural conditions. AB - Basic knowledge about the survival of free living stages of ticks is of great importance as a practical tool to improve control methods. For Anocentor nitens there is little information on this subject. Eighty-four engorged females were incubated at 30 degrees C and 100% relative humidity. After 17 days, groups of 5,500 eggs each were collected and isolated in vials. Age zero was defined as 10 days after eclosion had begun. At this time vials with larvae were attached to 40 Sorghum halepense plants sowed in clay pots, under outdoor conditions, and separated from one another by 30 cm in order to prevent the larvae from mixing. Four hours later vials were retired and the larvae remaining in the vials were counted. The next day four plants were sampled and this survival considered as 100%. Each week for eight weeks the same sampling procedure was performed. The remaining four plants were used to determine the maximum larval survival (MLS). Four repetitions of the procedure were performed, two in March 1989 and two in September 1989. PMID- 11193639 TI - International trade. Multinational aspects. AB - Of numerous regional economic agreements, the European Union (EU), the North American Free Trade Agreement (NAFTA), South American Common Market (MERCOSUR), the Association of Southeast Asian Nations (ASEAN), the South Asian Association for Regional Cooperation (SAARC) and the Australia-New Zealand Closer Economic Relations Agreement are examples that are actively pursuing regional integration for freer trade of animals and animal products. The World Trade Organization (WTO) believes that regional and multinational integration initiatives are complements rather than alternatives in the pursuit of more open trade. In the efforts to harmonize SPS standards among multilateral trading nations, it is recommended that national requirements meet the standards developed by the OIE and the FAO/WHO Codex Alimentarius Commission as the minimum requirements rather than adopting the standards of the lowest common denominator. Regional grouping may hinder multilateral or bilateral trade between the countries of a group and those of the other groups. How to eliminate such non-tariff barriers as traditional trade custom remains to be examined. Ongoing activities of VICH (Harmonisation of Technical Requirements for Registration of Veterinary Medical Products) may pave the way for more open trade in pharmaceutical products between multilateral regional groups. PMID- 11193641 TI - Tropical bont tick (Amblyomma variegatum) eradication in the Caribbean. The St. Kitts experience. AB - The tropical bont tick (TBT) was first identified in St. Kitts in 1978. Initially, infestation was observed on cattle that developed a severe dermatitis. Over a period of seven years, the TBT spread to most areas of the island, affecting cattle, sheep, and goats. The ruminant livestock population declined from, 6,000, 9,000, and 7,000 cattle, sheep, and goats, respectively, in 1984 to an estimated 400, 800, and 1,000, cattle, sheep, and goats in 1990. A project to control the tropical bont tick on St. Kitts was implemented in 1983. This effort was based on the use of plunge dips located in communal grazing areas. In October of 1995, the Caribbean Amblyomma Programme was initiated on St. Kitts to eradicate the TBT from the Caribbean. In 1996, there were 416 animal owners with 2,000, 4,300, and 4,000 cattle, sheep, and goats, respectively. Cases of dermatophilosis, declined from 657 in 1995 to 153 in 1996. During the period 1997 to 1998 treatment with Flumethrin continued. The Department of Agriculture initiated activities for treatment compliance, monitoring, and TBT surveillance. The animal population increased to 3,000, 6,000, and 4,500 cattle, sheep, and goats, respectively, and with 810 animal owners participating. The number of cases of dermatophilosis declined to 42. In 1998, the TBT was confined to three foci. The remainder of the island was declared provisionally tick free. PMID- 11193642 TI - The eradication of contagious bovine pleuropneumonia from south western Africa. A plan for action. AB - Contagious bovine pleuropneumonia (CBPP) caused by the Mycoplasma mycoides subspecies mycoides SC is one of the major plagues affecting cattle. With the imminent eradication of rinderpest from Africa, CBPP will become the major epidemic disease on the continent, because the majority of countries in sub Saharan Africa have the infection in their cattle. There is an enclave of CBPP on the borders of Angola, Botswana, Namibia, and Zambia. There has been endemic infection in the cattle herds on the borders of Angola and Namibia for more than 100 years, with irregular spread from these animals to the cattle of Botswana or Zambia. However, much of Angola and Namibia and all of Botswana and Zambia are currently free from the disease. This paper explains the origins of the problem and describes the current disease situation. A plan for the eradication of CBPP from this area is proposed and discussed. If this plan is successful it will release valuable resources to tackle other constraints on livestock and food production. Furthermore, it will act as a model for the eradication of CBPP from the remainder of the continent. PMID- 11193643 TI - At the end of the day. The socioeconomic impacts of eradicating contagious bovine pleuropneumonia from Botswana. AB - In February 1995, an outbreak of contagious bovine pleuropneumonia occurred in the Northwest district of Ngamiland, Botswana. The government of Botswana determined to eradicate the disease by depopulating the entire district of cattle. In total, 320,000 cattle were destroyed. Measures were put in place by government to mitigate the effects of eradication on the affected communities and household monitoring was instituted. This paper reports the major findings of the monitoring exercise. It is observed that although 45% of households said they would rely on arable cropping as a coping strategy, only 29% expected to produce sufficient food for themselves. Use of permanent, male agricultural labor fell by 33%, whereas both permanent and temporary female labor increased substantially. Although eight out of ten respondents planned to rebuild their herds, routine household demands on the generally small cash compensation received suggest that economic recovery for many of Ngamiland's households is likely to be prolonged. It is recommended that relief programmes continue but with improved targeting. Objective indicators are needed to determine when government assistance can be terminated. PMID- 11193644 TI - Mammalian reservoirs and epidemiology of rabies diagnosed in human beings in the United States, 1981-1998. AB - Between 1981 and 1998, 37 cases of rabies were diagnosed in human beings in the United States. Information directly linking the cause of infection to animal bite was available for only eight of these cases. Indirect incrimination of the vector by analysis of cDNA sequences obtained by reverse transcriptase polymerase chain reaction of samples indicated that for all cases (12/12) believed to have been acquired in foreign countries, variants of the rabies virus (VRVs) associated with dogs (7/12 involved known bite histories) were the cause of the rabies infections. In contrast, VRVs associated with bats (bat-associated VRVs or BAVs) were implicated as the cause of 88% (22/25) of infections believed to have been acquired within the United States (1/22 involved known bite histories). Sequence analyses revealed that a single BAV (Ln/Ps), associated with rabid silver-haired (Lasionycteris noctivagans) and Eastern pipistrelle (Pipistrellus subflavus) bats, was implicated in 73% (16/22) of bat-associated infections. Silver-haired bats are predominantly solitary and migratory. Eastern pipistrelle bats may occur individually or in small clusters. Both species are only infrequently submitted for rabies testing. Unrecognized bites and unique properties of the Ln/Ps BAV may explain its association with the majority of rabies infections in human beings in the United States. PMID- 11193645 TI - Emergence of Nipah virus in Malaysia. AB - A pig-borne virus causing viral encephalitis amongst human beings in Malaysia was detected in 1997 by the Ministry of Health. Initially, the disease was considered to be Japanese encephalitis. Subsequently, it was thought to be a Hendra-like viral encephalitis, but on 10th April, 1999 the Minister of Health announced this mysterious and deadly virus to be a new virus named Nipah virus. The virus was characterized at CDC, Atlanta, Georgia. The gene sequencing of the enveloped virus revealed that one of the genes had 21% difference in the nucleotide sequence with about 8% difference in the amino acid sequence from Hendra virus isolated from horses in Australia in 1994. The virus was named after the village Nipah. In all, the Ministry of Health declared 101 human casualties, and 900,000 pigs were culled by April, 1999. The worst affected area in Malaysia was Negri Sembilan. The symptoms, incubation period in human being and pigs, animal to human transmission, threat of disease to other livestock, and control program adopted in Malaysia is described. PMID- 11193646 TI - Evaluation of a new sandwich ELISA kit that uses serum for detection of cattle persistently infected with BVD virus. AB - Cattle immunotolerant to and persistently infected (PI) with bovine viral diarrhea (BVD) virus (BVDV) constitute the mechanism by which BVDV persists in and spreads among cattle herds. Detection and elimination of PI cattle are necessary for control of BVD. Serum is an excellent specimen for BVD PI testing because of high survivability of BVDV in serum and ease of collection, storage, and handling. Currently, microtiter virus isolation (VI) employing serum and sandwich ELISAs (S-ELISA) on tissues or leukocytes are used for BVDV PI screening. This paper evaluates a new S-ELISA kit that uses serum as the diagnostic sample. Cattle sera (n = 408) were tested using VI and the S-ELISA. The VI detected 172 BVDV-positive sera. Of these, 18 were confirmed PI cattle. The S-ELISA was positive on all PI samples. Considering only the PI animals, and using VI as the gold standard, the relative sensitivity of S-ELISA was 100%. The overall relative sensitivity was 93.6% and the agreement quotient (kappa) was 0.94. The relative specificity of the kit, based on 236 VI-negative sera, was 100%. These data indicate that the new kit is very adequate for detection of BVDV PI cattle. PMID- 11193647 TI - The impact of diseases on the importation of animals and animal products. AB - For decades the veterinary services of the United States and other nations protected their livestock and poultry industries from the ravages of introduced animal diseases by rigorous import restrictions. This policy of zero risk frequently translated to no or reduced trade in animals and animal products or dramatic trade inequities. However, GATT articles enforced by the WTO require that imported products be treated no less favorably than domestically produced goods with regard to animal health restrictions. Under authority from the WTO, the OIE establishes recommendations and guidelines for the regulation of trade in animals and products of animal origin through the OIE International Animal Health Code, sets animal health standards, and reports global animal health situations and statuses. Diseases often have a dramatic impact on the animal agricultural industries of a nation--disease outbreaks may be deleterious to the competitiveness of the products of one nation but offer opportunities for others. The potential dangers of lax vigilance, insufficient scientifically valid data, inadequate SPS measures, and errors in assessing risk can turn the heady experience of seemingly unlimited growth in international markets and demand for one's products into a catastrophic return to reality. The experience of the United Kingdom and countries of Europe with bovine spongiform encephalopathy is a case in point. It is estimated that the cost of the outbreak of this disease to the economy of the UK has been more than $3 billion. Responses of their trading partners, including the US, to this outbreak were abrupt and restrictive. Although the decision was controversial, the US stopped importation of live cattle from the UK in the late 1980's and subsequently, in 1997, importation of all products of ruminant origin was stopped from all countries of Europe. The transmission of the disease to continental Europe and the disclosure that the pathogen was associated with a fatal human illness, rocked consumer confidence in the safety of the UK beef supply, brought down the ruling political party in the UK, and forced major changes in the beef industry. PMID- 11193648 TI - Comparison between c-ELISA and CFT in detecting antibodies to Mycoplasma mycoides mycoides biotype SC in cattle affected by CBPP in Botswana. AB - Contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides mycoides biotype small colony (SC) (MmmSC) appears to be making a serious comeback in Africa after successful control programs in many parts of the continent during the 1960s and 1970s. Botswana, a country that has been free from the disease for more than 50 years, was affected in 1995. An eradication policy was adopted by the Government of Botswana in which 320,000 cattle in the affected district of Ngamiland, Northwestern Botswana were slaughtered. This was followed by a restocking exercise in which 70,000 cattle were sent to the outbreak areas as replacement stock. It became necessary to carry out serosurveillance in order to ensure that the disease did not reenter Botswana and to ensure that the replacement stock remained free from the disease. The specificity and sensitivity of the complement fixation test (CFT) in Botswana was assessed in 82 cattle affected by the disease and held in a double fenced quarantine camp. The newly developed competitive ELISA was made available to the National Veterinary Laboratory (NVL) through the FAO/IAEA Joint Division in Vienna, Austria. Using postmortem lesions as the gold standard and a 2 x 2 contingency table, the two tests were compared in terms of their sensitivity and specificity in detecting antibodies to MmmSC. The CFT was found to be slightly more sensitive than the c ELISA, and this could be related to the stage of the disease. A long-term study comparing the progression of the disease with the two tests is, therefore, essential. PMID- 11193649 TI - Conservation medicine. AB - The Field Veterinary Program (FVP) of the Wildlife Conservation Society (WCS) was created in 1989 to combat the wildlife disease and health problems that increasingly complicate the process of wildlife conservation. The FVP provides veterinary services for the more than 300 WCS conservation projects located in more than 50 countries around the world. Most of these projects are in tropical regions and many have a wildlife/domestic livestock component. Wildlife health care provided by the FVP staff includes (1) identifying critical health factors; (2) monitoring health status; (3) crisis intervention; (4) developing and applying new technologies; (5) animal handling and welfare concerns; and (6) training. Additionally, the staff of the FVP give expert advice to many governmental and non-governmental agencies that are involved in setting policies directly related to wildlife health and conservation issues. In this paper, two FVP projects are presented as examples of studies that have increased our understanding of the role wildlife diseases may play in the health of livestock and human populations, as well as the role humans and livestock may play in the health of wildlife populations. Examples of the collaborative work between the FVP staff and scientists from many disciplines (e.g., acarologists, mycobacterium experts, ecologists, and biologists) are also presented. PMID- 11193650 TI - Detection of mucosally delivered antibody to Cryptosporidium parvum p23 in infected calves. AB - We have developed an assay to detect mucosally delivered antibody to Cryptosporidium parvum sporozoite antigens. We absorbed a recombinant 23-kD sporozoite protein to polystyrene microspheres, and used flow cytometry to detect, titer, and determine the isotype of antibody to p23 that was shed in the feces of experimentally infected calves. Noninoculated calves have low levels of mucosal antibody to p23, with IgG1 as the predominant isotype. Antibody titers rise in inoculated calves as the animals recover from cryptosporidiosis. A calf that was naturally protected from cryptosporidiosis had mucosal IgM and IgG1 isotype anti-p23 antibodies prior to challenge with C. parvum oocysts. Ten days after challenge, the calf had high titers of IgM, IgA, IgG1, and IgG2 anti-p23 antibodies. Together, the data show that this method can be used to assess mucosally delivered antibody to C. parvum. PMID- 11193651 TI - A study on the time of ovicidal effect of some anthelmintics in Djallonke sheep and its implication for the control of parasitic helminth infections. AB - The time lag between the administration of five different anthelmintics and the exertion of their ovicidal effect on worm eggs was monitored in five groups of Djallonke sheep. In this experiment, all the animals in all treated groups and an untreated control group were grazed together. Worm egg output and the number of infective strongylate nematode larvae (L3s) recovered from fecal cultures from each group were observed every four hours for 72 h. The earliest time observed for the occurrence of ovicidal effect resulting in the absence of L3s in fecal cultures was 8 h after the administration of the anthelmintics. However, this time was not the same for all the anthelmintics. The implication of the results are discussed in relation to its application for worm control. PMID- 11193652 TI - Standardization of the diagnostic criteria for canine ehrlichiosis. Towards a universal case definition. AB - Canine ehrlichiosis is a highly variable syndrome presenting a significant differential diagnostic difficulty. It imitates many metabolic and infectious diseases and lacks standardized diagnostic criteria, common reagents, and database resources. A clinical diagnosis of canine ehrlichiosis may be based on the manifestation of fever, thrombocytopenia, anorexia, nasolacrimal discharge, epistaxis, and exclusion of autoimmune and common canine vector borne diseases. These parameters are not invariably observed especially in the atypical form of the disease often caused by species other than Ehrlichia canis. A definitive diagnosis is based on the presence of specific antibodies to ehrlichial agent(s), the demonstration of the etiologic agent(s) itself, or specific amplicons by a strigently quality controlled PCR protocol. The relationship of the various clinical and laboratory parameters, the status of the currently available tests, and their real or presumed predictive value are discussed in the context of stimulating an effort to formulate an international standard for the diagnosis of this and related diseases of man and animals. PMID- 11193653 TI - Ten years of research activities on tropical parasitology of dromedaries, cattle, and small ruminants in Mauritania. AB - In the past, the essential part of the activity of the parasitology laboratory of the Centre National d'Elevage et de Recherches Veterinaires (CNERV) was represented by diagnostic work that enabled the construction of an inventory of local parasitic fauna and a good collection of specimens. However, the small and irregular number of samples each year, led us to switch our activities in 1990 toward work that could better justify the existence of CNERV. We started work on applied research topics, such as tick-borne diseases, helminthology (nemathelminths and plathelminths), and trypanosomosis. These results were valorized through scientific publication and communication at international meetings. The most valuable information was conveyed to herders. PMID- 11193654 TI - A perspective on animal protein production in sub-Saharan Africa. AB - A large survey of animal protein production in sub-Saharan Africa was performed. The objective was to identify specific production needed to ensure sustainable development. Starting from data collection and analysis to gain control of this information, the study proposes possible paths of evolution for supply and demand for animal production. Africa will be the continent where the demand will grow the most (together with Asia), because of demography and urbanization. Urbanization will represent an extraordinary opportunity for the development of animal production. In 2020, the global demand will be 20 million tons per year (7.3 in 1994) for meat, 45 million tons for milk (18.6 in 1994) and 2.9 million tons for eggs (1.1 in 1994). Red meat, which now provides 55.6% of present meat consumption will satisfy only 36.5% in 2020. This underlines the immense effort needed to intensify ruminant production and/or to develop monogastric production. Consequently, there is a need in tropical animal health and research for better knowledge and control of monogastric diseases and particularly those linked to intensification. The development of peri-urban milk production will require particular attention to hemoparasitic diseases. Globally, there is an urgent need to set up projects for the development of animal production. PMID- 11193655 TI - Development of a molecular probe to baboon interleukin-10 mRNA for in situ hybridization during experimental schistosomiasis. AB - A nucleic acid probe complementary to baboon interleukin 10 (IL-10) mRNA was developed for in situ hybridization. Highly conserved IL-10 protein sequences from several mammals were aligned to design oligonucleotide primers flanking a 270-bp sequence of the target cDNA. RNA was isolated from stimulated peripheral blood mononuclear cells (PBMC). IL-10 cDNA was reverse-transcribed from the total PBMC RNA and amplified with the polymerase chain reaction (PCR). Cloning and sequencing of the PCR product confirmed it to be of baboon IL-10 origin, with 97.8% identity to human and 100% identity to macaque mRNA sequences. The baboon IL-10 DNA probe hybridized in Southern blots to a 7.9-Kbp or 8.6-Kbp band after digestion of genomic baboon DNA with Bam H1 or Eco R1, respectively. Preliminary results with an antisense riboprobe derived from this sequence showed the presence of IL-10 mRNA in sections of granulomatous tissues. PMID- 11193657 TI - VSV-NJ on Ossabaw Island, Georgia. The truth is out there. AB - Ossabaw Island, Georgia, is the only recognized enzootic focus of vesicular stomatitis virus New Jersey (VSV-NJ) in the United States and has been the subject of VSV-NJ research since 1981. To date, VSV-NJ antibodies have been detected only from feral swine, cattle, equines, deer, and raccoons. VSV-NJ transmission occurs annually, is seasonal, and is associated with the maritime forest. Despite high transmission rates the clinical disease is rarely detected. A sand fly (Lutzomyia shannoni) occurs on the Island, and experimental and field data suggest that it is a biological vector of VSV-NJ at this site. Many questions relating to the epidemiology of VSV-NJ on Ossabaw remain. What is the maintenance cycle of VSV-NJ? Is a vertebrate amplifying host(s) needed? Are other insect vectors involved in mechanical or biological transmission? Why do vesicular lesions develop on some but not all infected animals? Do native and domestic animals play the same role in the maintenance cycle? These questions challenge researchers in all areas where VSV-NJ occurs. It is our hope that Ossabaw Island will provide a much needed model system for gaining insight into the epidemiology of this virus. PMID- 11193656 TI - Longitudinal studies in the epidemiology of vesicular stomatitis on Costa Rican dairy farms. AB - Twenty-three Costa Rican dairy herds from an vesicular stomatitis (VS) endemic area were under an active surveillance between April 1997 and March 1999. Ninety two confirmed cases of VS New Jersey were found. Factors associated with clinical cases of VS virus New Jersey were: Parity (animals of parity 4 or 5 were 5.3 times more likely to present a clinical case than animals of parity 3 and lower; on the other hand, animals of parity 6 and higher showed an odds 4.6 times greater than animals of parity 3 and lower.) Ecological life zone (animals in premountain moist forest were 7.4 times more likely to present clinical cases than animals in lower mountain rain forest). Factors associated with seropositivity at the time of birth were farm and breed (Jersey calves had an odds 14.7 times greater than Holstein calves). Seroconversion, defined as the first twofold increase in the titers of the blood, was associated with farm and showed four peaks during the study period, September (wet season) 1997, February (dry season) 1998, September 1998, and February 1999. Finally, time to event analysis showed difference between farms and age, older animals showed the first seroconversion earlier than younger animals. PMID- 11193658 TI - Laboratory vector competence of black flies (Diptera:Simuliidae) for the Indiana serotype of vesicular stomatitis virus. AB - In previous experiments we have demonstrated that colonized and wild black flies are competent laboratory vectors of different Mexican and Western USA isolates of vesicular stomatitis virus, serotype New Jersey (VSV-NJ). We have recently demonstrated biological VSV-NJ transmission by black flies using animal models. In the study described here, we tested the vector competence of colonized and wild black flies for the vesicular stomatitis virus, serotype Indiana (VSV-IN). A 1998 equine isolate was used. After a 10 day incubation period, saliva from experimentally infected Simulium vittatum and S. notatum was individually collected and tested for the presence of infectious virus. Virus was detected in the saliva of both species following oral infection, indicating that they are competent laboratory vectors of VSV-IN. In addition, the results suggest that the black fly gut may exert evolutionary pressures on the virus. PMID- 11193659 TI - Pharmacological factors in the saliva of blood-feeding insects. Implications for vesicular stomatitis epidemiology. AB - Vesicular stomatitis (VS) epizootics in the Western United States have caused substantial economic losses to U.S. livestock industries in 1995, 1997, and 1998. The role of arthropods in transmitting VS to U.S. livestock is unclear. In particular, the impact of arthropod salivary gland factors in VS infections in livestock needs study. Pharmacological effects of arthropod salivary gland factors on animals are reviewed. The potential effects of arthropod saliva on the transmission and spread of VS virus to livestock in the Western U.S. is presented with emphasis on the biting midge, Culicoides sonorensis. Information is discussed with attention to vector potential of C. sonorensis, and its use as a model for evaluating insect salivary gland pharmacology on livestock response to VS. PMID- 11193660 TI - Survey of small rodents and hematophagous flies in three sentinel farms in a Costa Rican vesicular stomatitis endemic region. AB - A survey of rodents and hematophagous flies was conducted on three farms located in an area endemic for vesicular stomatitis to determine the species composition of each zoological group occurring in these areas. Eleven species of small rodents were collected and identified. Individuals from forty-nine species of hematophagous flies of the families Ceratopogonidae, Culicidae, and Phlebotominae were captured and identified. The species compositions in each group were compared between farms. Rodents were tested for antibodies to vesicular stomatitis, New Jersey and Indiana serotypes. Seven species had antibody titers greater than 1:10. Attempts to isolate the virus produced negative results for all the species tested. PMID- 11193661 TI - Vaccines against Theileria parva. AB - Bovine theileriosis caused by Theileria parva continues to be a major economic problem in many parts of Eastern, Southern, and Central Africa. Due to the unsustainable nature of the present control method--using toxic acaricides to kill ticks--alternative control methods are being sought. Live vaccines are being used in many countries in the region. These vaccines are based on the infective sporozoite stage of the parasite. Sporozoites are inoculated in cattle with simultaneous administration of a long-acting formulation of oxytetracycline. These vaccines are poorly adopted in the region, mainly because of problems associated with the use of live parasites. An experimental recombinant vaccine based on a sporozoite surface antigen (p67) has been developed. Immunization with this antigen induces neutralizing antibodies and, under laboratory conditions, this technique protects approximately 70% of the immunized cattle to a defined needle challenge. The efficacy of the vaccine is currently being evaluated under field challenge in Kenya. Since a vaccine based on a single antigen may not be sustainable under field conditions, a search for schizont antigens that induce protective cell-mediated immune responses continues. It is expected that the ultimate vaccine against theileriosis will incorporate a mixture of several antigens derived from both sporozoite and schizont stages, contributing to robust immunity. PMID- 11193662 TI - Anaplasmosis control and diagnosis in South Africa. AB - Anaplasmosis is widespread in South Africa with more than 99% of the total cattle population at risk. Five tick species have been experimentally shown to be capable of transmitting Anaplasma in South Africa. Mechanical transmission through blood contaminated instruments and biting flies also occurs. Vaccination against Anaplasma marginale by administration of an Anaplasma centrale live-blood vaccine has been practiced in this country since 1912. Although generally a mild pathogen, Anaplasma centrale can cause severe clinical reactions following vaccination and also does not afford complete protection against all A. marginale isolates. Anaplasmosis vaccine is routinely available in a deep-frozen form and approximately 220,000 doses of vaccine are sold per annum. Microscopic examination of stained thin blood smears is still the most reliable and cost effective method of confirming a clinical diagnosis of anaplasmosis. Several diagnostic tests, such as the complement fixation tests, card agglutination test, and enzyme-linked immunosorbent assay (ELISA) have been developed to identify carrier cattle. A competitive inhibition ELISA test, based on antibody binding to a recombinant MSP-5 protein conserved among Anaplasma species, is routinely used at this laboratory. PMID- 11193663 TI - Vaccination against tropical theileriosis. AB - Theileria annulata, the cause of tropical theileriosis is propagated in cattle with stage-to-stage transmission by Hyalomma ticks. Three stages in the life cycle of the parasite--tick-derived sporozoites, intramononuclear schizonts, and erythrocytic merozoites--infect cattle. When cattle are inoculated with schizont infected cells, the parasite is transferred from the donor cell to the recipient. The main pathological damage in cattle is induced by the schizont stage. Each development stage of T. annulata elicits a specific immune response. Schizont infected lymphoid cells can be grown indefinitely in culture and prolonged cultivation results in loss of virulence. Blood-derived schizonts induce stronger immunity than culture-derived schizonts, which suggests that restrictions on the parasite population or antigenic variation occur during prolonged cultivation. The duration of immunity following sporozoite or schizont infections has not yet been determined, but does not appear to be lifelong. The attenuated, culture derived anti-theileria vaccine proved to be safe and effective in prevention of field theileriosis in large enzootic areas. PMID- 11193664 TI - OIE List A disease as a constraint to international trade. AB - World Trade Organisation agreements have swept aside many of the previous constraints to international trade in animals and animal products and have looked critically at those that still survive. The presence of disease, in particular the OIE list A diseases, still provide legitimacy for barriers to trade, and as a consequence the importance of reliable animal disease surveillance has increased. However, the economic consequences of reporting the occurrence of a List A disease have also increased, as this provides trading partners with sufficient reason to impose an embargo that could severely compromise the national agricultural industry. The dilemma for some developing economies, reliant on agricultural exports, is how to balance a transparent and efficient disease reporting service, sufficient to provide the necessary information for importing countries to make realistic risk assessments, with the perceived political damage from being honest with trading partners who might take advantage of the information to require additional safeguards and health certification. PMID- 11193665 TI - Anaplasmosis control. Past, present, and future. AB - Control methods for anaplasmosis have not changed markedly during the past 50 years and include arthropod control, chemoprophylaxsis, vaccination, and maintenance of an Anaplasma-free herd. Control measures implemented vary with geographic location, and depend on availability, cost, and the feasibility of application. Vaccination has been an effective means of preventing outbreaks of anaplasmosis, but these vaccines, both live and inactivated, are dependent on bovine blood as the source of infection or antigen. Blood-derived vaccines are difficult to standardize and bear the risk of transmitting other bovine pathogens inapparent at the time of blood collection. Extensive purification is required to remove bovine cell membranes, which may cause side effects. Most importantly, geographic isolates of A. marginale are often not cross-protective. Development of a tick cell culture system for A. marginale shows promise as a source of antigen for development of an improved inactivated vaccine in the near future that is free from bovine pathogens. Development of an antigenically defined molecular vaccine appears to be a realistic goal, although further research is required to determine epitopes involved in both humoral and cellular immunity, to define antigenic variation during cyclic rickettsemia, and to develop effective delivery systems for optimization of the immune response. PMID- 11193666 TI - Babesiosis (Babesia bovis) stability in unstable environments. AB - Enzootic stability (herd immunity) in bovine babesiosis occurs when the rate of transmission (inoculation rate) of Babesia spp by the tick vector is sufficient to immunize a majority of susceptible calves before the loss of calfhood resistance. The effect of three tick (Boophilus microplus) control strategies (none, threshold, and strategic) on enzootic stability and the likelihood of babesiosis (Babesia bovis) outbreaks was studied using a spreadsheet age-class computer simulation model. The model was driven by weekly bovine tick counts from Brazil and Uruguay. The Eldorado do Sul, RS, Brazil bovine population (30 degrees 05' South latitude) was found to be in a naturally occurring state of enzootic stability, corresponding to an inoculation rate exceeding 0.005 throughout the year. Threshold dipping strategies should not increase the risk of babesiosis in cattle so managed. Strategic dipping resulted in an extended period of enzootic instability lasting 30 weeks, which requires protection of the herd through immunization. Because of the more prolonged low winter temperature conditions, the Tacuarembo, Uruguay bovine population (31 degrees 40' South latitude) was found to be in a naturally occurring state of enzootic instability, characterized by a 28 week period in which the inoculation rate was below 0.005. Strategic dipping should lead to eradication of the babesial parasite from tick and bovine populations, but would not result in eradication of the tick vector. This could lead to subsequent outbreaks if Babesia carrier animals were to be introduced into the herd. In both populations, strategic tick control could be accompanied by concurrent babesiosis vaccination. PMID- 11193667 TI - Characterization of attenuated Theileria annulata vaccines from Spain and the Sudan. AB - Theileriosis caused by Theileria annulata can be effectively prevented by vaccination with attenuated, cultured schizonts. Although these attenuated vaccines have been applied for a long time, not much is known about the fate of the vaccine strain in the field. Here, two experimental Spanish vaccine strains originating in Cadiz and Caceres, and one Sudanese strain are studied to address the development of a carrier status and the infectivity for Hyalomma ticks. Moreover, the heterogeneity of the merozoite surface protein, Tams1, was analyzed in search for an attenuation marker. Using the sensitive reverse line blot (RLB) hybridization, the development of a low level carrier status was demonstrated in the Caceres and Sudanese line vaccinated calves. Although no signal was detected in the Cadiz line vaccinated calves, seroconversion against the schizont stage was observed, as it was in all other calves. The experimental transmission of T. annulata by Hyalomma ticks to naive calves was unsuccessful for all cell line inoculated calves. Tams1 heterogeneity indicated a clonal selection of parasites during the process of attenuation, but the Tams1 sequence itself has no connection with the attenuation status. In conclusion, a carrier status develops in attenuated schizont culture vaccinated calves, but is not infective for Hyalomma ticks. Based on these data, the risk for spread of the vaccine strains in the field may be very low. PMID- 11193668 TI - Integrated molecular diagnosis of Theileria and Babesia species of cattle in Italy. AB - A reverse line blot hybridization (RLB) test was developed to specifically identify six Theileria spp. (T. annulata, T. parva, T. mutans, T. velifera, T. taurotragi, and T. buffeli/orientalis) and three Babesia spp. (B. bovis, B. bigemina, and B. divergens). No cross reaction was observed with other livestock pathogens (such as Anaplasma marginale, A. centrale, A. ovis, Cowdria ruminantium, Trypanosoma brucei, T. congolense, and T. vivax). This method was used to test bovine blood samples collected in Sicily in April and November, 1998. Preliminary results indicated that T. annulata and T. buffeli/orientalis were the main species observed in cattle blood. Babesia species represented 1.8% and 23.5% in April and November, respectively. PMID- 11193669 TI - Vaccination against bovine babesiosis. AB - Bovine babesiosis is an important disease caused by Babesia bovis, B. bigemina, and B. divergens. Solid immunity develops after infection and this feature has been exploited with the use of live attenuated organisms as immunogens. Attributes of live vaccines include a durable immunity to heterologous challenge after one vaccination. To overcome disadvantages relating to poor quality control (risk of contamination and adverse reactions), production procedures have been modified to meet the requirements of codes of good manufacturing practice. This includes development of methods to allow production of cryopreserved vaccine and limit antigenic drift. Killed vaccines have also been used on a limited basis and consist of antigens extracted from cultured material or blood of infected calves, and given with adjuvant. The degree and duration of immunity against heterologous challenge is not well documented. Attempts are being made to develop subunit vaccines but the progress has been slow. A better understanding of the mechanisms involved in the expression of protective immunity against Babesia spp will aid in the identification of protective antigens. PMID- 11193670 TI - Past and present national tick control programs. Why they succeed or fail. AB - The historical reasons for the introduction of tick control during the nineteenth century are reviewed. Background and concepts for the choice between long-term tick control and tick eradication are compared. Case studies of large-scale tick control or eradication programs in Africa, Australia, the United States, and the Caribbean are used to highlight successes and failures. The main reasons for lack of sustainability, or failure, of programs are discussed. These include the economic constraints that were faced in several African countries, or technical shortcomings such as were perceived as a major problem in Puerto Rico. The successes are generally associated with enforcement of appropriate legislation and good management, such as occurred in Zimbabwe. These case studies are analyzed to identify features that may assist in the implementation of the ongoing tropical bont tick eradication program in the Caribbean. The paper concludes with some practical suggestions for the future, and the need to reassess the economics of control and the potential additional animal health benefits derived from tick control programs. PMID- 11193671 TI - The increasing significance of international trade in equids and its influence on the spread of infectious diseases. AB - Expansion in international trade in equids and equine semen has been especially notable over the past 10-15 years among those countries historically identified as having significant breeding and performance horse industries. The continuing trend towards globalization of the horse industry received additional impetus in January, 1995, following establishment of the World Trade Organization (WTO), whose primary goal is to promote freer economic exchange between member countries through the reduction or elimination of protectionist barriers to trade. Continued growth in international trade, closely related to changing trends in the horse industry, has greatly increased the risk of spread of a wide range of equine infectious diseases between countries. In consequence, the global distribution of certain of these diseases is likely to change in the future. Within the past 30-40 years, there have been numerous confirmed instances of the spread of specific diseases through the international movement of equids or shipment of semen, some of which have resulted in epidemics of major economic importance. Under the Sanitary-Phytosanitary Agreement of the WTO, national agencies have had to rethink their traditional "zero-risk" approach in regulating the importation of equids or equine semen from other countries. Mindful of the risks of disease spread inherent in such transactions, authorities must now accept that primary emphasis in today's global economic climate must be on greater facilitation of trade, rather than attempting to provide absolute disease preventive safeguards. PMID- 11193672 TI - Trials to control South American ticks with entomopathogenic fungi. AB - Ticks are parasites of great importance to man, domestic, and wild animals. In spite of the progress of the science, thus far, ticks are controlled mainly by chemical acaricides and when this technique is used in an indiscriminate way it can lead to ambiental pollution and development of tick resistance to acarcides. The studies developed in the Universidade Federal Rural do Rio de Janeiro demonstrate that some isolates of the fungi Metarhizium anisopliae and Beauveria bassiana are pathogens for ticks and their action effects the mortality of ticks and reduces the populational levels in subsequent generations. In future, research needs to address the search of new pathogens; the association of biological with chemical products seeking an synergistic action; the search of formulations that propitiate increased stability, and careful studies on the safety of biological products for use in animals. PMID- 11193673 TI - Laboratory and field evaluation of entomogenous fungi for tick control. AB - Aqueous and oil-based formulations of two entomogenous fungi, Beauveria bassiana and Metarhizium anisopliae were tested for their efficacy against the three major species of African ticks; namely, Amblyomma variegatum, Rhipicephalus apendiculatus, and Boophilus decoloratus. Both fungal species and formulations were observed to induce high mortalities, especially in the larvae. The oil-based formulation was found to be more effective than the aqueous formulation. Monthly application of aqueous formulations of B. bassiana and M. anisopliae on vegitation in paddocks significantly reduced numbers of the tick R. appendiculatus on cattle. Possibilities for using entomogenous fungi in tick control, alone, or in combination with the conventional acaricides are discussed. PMID- 11193675 TI - Skin test and tick immune status in susceptible and resistant cattle in Brazil. AB - A cutaneous hypersensitivity test (CHT) was used to correlate host resistance to ticks and type of reaction elicited to unfed larval extract-ULE of the cattle tick Boophilus microplus in European and Indian cattle. Twenty calves were separated into four groups of five animals each: naive or preinfested Indian or European cattle. CHT was induced by intradermal inoculation of 0.1 ml of ULE cattle tick B. microplus (50 micrograms protein) in the calf ear. Ear thickness was measured using calipers before and 10 min, 1, 2, 6, 18, 24, 48, 72, 96, and 144 h postinoculation (PI). Preinfested European calves showed only an immediate type reaction with maximum response (75% increase in ear thickness) at 10 min PI. On the other hand, preinfested Indian calves presented an immediate response with maximum reaction (70% increase in ear thickness) between 10 min and one hour PI, and a delayed type reaction at 72 h PI (60% increase in ear thickness). These results point out the crucial role of the cellular immune response of cattle in the expression of resistance to cattle tick B. microplus. Skin test might be useful in the ranking of cattle according to the susceptibility/resistance to ticks. PMID- 11193674 TI - Role of grooming in biological control of ticks. AB - Although many species of wild bovids live in tick infested environments, tick loads are usually kept to very low levels, primarily by frequent self grooming. Evidence from numerous studies on antelope in Africa strongly support the concept that the delivery of bouts of grooming reflects programmed grooming rather than stimulus driven or reactive grooming. In other words, grooming occurs in response to an endogenous generator that produces grooming bouts at periodic intervals, resulting in removal of ticks before they attach and begin to feed. In the same tick exposure environment, animals that groom most have the fewest ticks. The rate of programmed grooming is modulated by a number of interspecific and intraspecific determinants. Interspecific determinants include adult body size and whether or not the evolutionary habitat is tick dense or tick sparse. Intraspecific determinants include developmental stage of growth, gender (e.g., territorial male vs. female), ectoparasite exposure, and stage of arousal. Some of the intraspecific determinants appear to be mediated by systemic physiological influences suggesting there may be ways to improve grooming activity in weak groomers, such as cattle. PMID- 11193676 TI - The potential for antitick plants as components of an integrated tick control strategy. AB - Extracts from various African plants have been shown to possess strong acaricidal and/or tick repellent properties. Some of the plant extracts are capable of reducing tick feeding, molting, fecundity, and viability of eggs. Pasture grasses capable of repelling, trapping, and killing ticks have also been reported. These grasses possess hairs (trichomes) that retard ticks from climbing to the top of the grasses in order to attach themselves to passing animals. Furthermore, some grass species, such as Stylosanthes, produce viscous fluids that poison and kill ticks. Results obtained with antitick plants are presented in this paper and feasibility of using them in an integrated tick control strategy is discussed. PMID- 11193677 TI - Present and future technologies for tick control. AB - Arsenic dips were the first effective method for controlling ticks and tick-borne diseases, and were used in many parts of the world for over 50 years before resistance to the chemical became a problem. Until organochlorine products became available about 1946 as alternatives to arsenic, significant losses occurred in cattle herds exposed to arsenic-resistant tick strains. Since the discovery of organochlorines, virtually every chemical group of pesticides developed for the control of arthropods is represented among the list of products employed for the control of ticks on cattle. The evolution of tick resistance to acaricides has been a major determinant of the need for new products. The variety of procedures for treating animals with acaricides ranges from dipping cattle to injecting systemic acaricides, but regardless of the treatment method used, producers need to know and follow proper application procedures to derive maximum benefits. The possibility of stocking with cattle breeds that acquire pronounced resistance to ticks or using recombinant antigen antitick vaccines are the most promising alternatives to acaricides. Most ranchers depend completely on acaricides to control ticks, but do not have access to guidelines on how to make a profit from their tick control program or how to detect and resolve problems with resistance to acaricides. Extension programs are needed to help ranchers manage animal health problems, including how to control ticks and tick-borne diseases. PMID- 11193678 TI - Biocontrol of ticks by entomopathogenic nematodes. Research update. AB - Entomopathogenic nematodes (EPNs) are lethal to ticks even though they do not use their normal propagation cycle within tick cadavers. The tick Boophilus annulatus was found to be far more susceptible to EPNs than Hyalomma excavatum, Rhipicephalus bursa, or Rhipicephalus sanguineus. Ticks seem to be less susceptible to nematodes when feeding on a host. Preimaginal tick stages were less susceptible to nematodes than adult ticks. The mortality rate of unfed females was highest, followed by unfed males, and engorged females. The virulence of nematodes to ticks varied greatly among different nematode strains. In most cases, the Heterorhabditis sp. strains were the most virulent strains tested in petri dishes. In buckets containing sandy soil sprayed with 50 nematodes/cm2 and engorged B. annulatus females, the LT50 of the ticks was less than five days. The addition of manure to soil or a manure extract to petri dishes reduced nematode virulence. Since ticks spend most of their life cycle in the upper humid layer of the ground, and many nematode strains share this same ecological niche, the use of EPNs for biocontrol of ticks appears promising. PMID- 11193679 TI - Generation of cytotoxic T lymphocytes and cytostatic acting cells in T. annulata immune cattle. AB - Cattle immunized against Theileria annulata with schizont containing autologous cell lines are immune to challenge with a homologous parasite strain. Two cell types have been detected in the peripheral blood of the immunized animals: cytotoxic T lymphocytes (CTL) and cytostatic acting cells (CAC). Killing the target cells by CTL is infection associated and is MHC class I restricted. Hence, no cytotoxicity was observed against target cells that were treated with the theilericidal drug buparvaquone or autologous Con A-blasts. The growth inhibition of CAC is MHC unrestricted, and not mediated by cytokine interferon gamma (IFN gamma). PMID- 11193680 TI - What and how do we communicate? AB - The rapid, inexpensive transmission of words and data, brought about by the internet and cheap computers, is changing the world faster than anything mankind has ever experienced, reaching into nearly every aspect of our lives, public and private, commercial and governmental. We are in an Information Age with an essentially instantaneous availability of large volumes of information and data. Technological pressures have their own momentum. The changes and improvements in data handling and information sharing will take place, however much or little we do in veterinary medicine, whether at the international or national levels. In addition, there are new superpowers emerging in the world. These are the small and medium third world countries that are gradually gaining democracy through political restructuring and involving the civil society in decision making. There are also the marginal pressure groups, once too small and insignificant to be noticed. These are changing the rules by which the way the world is governed and they are doing it now by the internet and banding together to serve their common interests. The rapid provision of accurate information on animal diseases is desirable goal from a public health as well as an economic viewpoint. PMID- 11193681 TI - Efficacy and safety of new adjuvants. PMID- 11193682 TI - Cross reactivity between instars of the Rhipicephalus sanguineus (Latreille, 1806) tick. PMID- 11193683 TI - Emerging diseases of Africa and the Middle East. AB - The term "emerging diseases" has been used recently to refer to different scenarios, all of which indicate changes in the dynamics of disease in the population. Of the OIE List A diseases, major changes have been experienced with rinderpest, peste des petit ruminants (PPR), contagious bovine pleuropneumonia (CBPP), foot-and-mouth disease, African swine fever, lumpy skin disease, and Rift Valley fever. Rinderpest represents a success story of the 1990s, thanks to the programs of the Pan African Rinderpest Campaign (PARC). The situation has changed from that of the 1980s when rinderpest was widespread throughout most of Tropical Africa and the Middle East. PPR is a disease that has become of increasing importance throughout Tropical Africa and the Middle East. CBPP, which had previously been reduced to sporadic incidence within endemic areas, invaded new areas, causing heavy mortality. African swine fever has extended to West Africa and to Madagascar, in both regions resulting in heavy losses. Climatic changes in both East and West Africa were associated with an upsurge of Rift Valley fever. Deficiencies in national veterinary services have contributed to failures in early detection and response; in many regions investigation and diagnosis services have deteriorated. The continuing structural adjustment program for national veterinary services will need to take into account their transformation from providers of services (e.g., vaccinations, medicines) to inspection and quality assurance services. Surveillance, early warning, and disease emergency preparedness will need to be pursued more vigorously in Africa and the Middle East as vital components of national veterinary services. PMID- 11193684 TI - Preliminary results of a larval resistance test to ivermectins using Boophilus microplus reference strains. PMID- 11193685 TI - Attenuated trivalent vaccine against babesiosis and anaplasmosis in Colombia. PMID- 11193686 TI - Immunological control of ticks through vaccination with Boophilus microplus gut antigens. AB - The control of tick infestations and the transmission of tick-borne diseases remain a challenge for the scientific community. Traditional control methods have been only partially successful. Recently, vaccination with recombinant Boophilus microplus gut antigens has been shown to control tick infestations. Our Bm86 containing vaccine formulation (Gavac) has been effective for the control of artificial infestations of B. annulatus, B. decoloratus, and chemically sensitive and resistant B. microplus strains from Australia, Africa, America, and Iran. Preliminary results with Hyalomma spp. and Rhipicephalus spp. suggest partial cross protection. In field trials, vaccination with Gavac controlled B. microplus and B. annulatus infestations and reduced the transmission of babesiosis, resulting in important savings for the cattle industry. Different degrees of susceptibility to the vaccination with Bm86 and sequence variations in the Bm86 locus have been reported. The Bm95 antigen was isolated from the Argentinean Bm86 resistant B. microplus strain A. A Bm95-based vaccine was used to protect cattle against tick infestations under production conditions with similar results to that obtained with Gavac. The Bm95 antigen from strain A was able to protect against infestations with Bm86-sensitive and Bm86-resistant tick strains, thus suggesting that Bm95 could be a more universal antigen in protecting cattle against infestations by B. microplus strains from different geographical areas. These results clearly demonstrate the advantage and possibilities for the immunological control of ticks. PMID- 11193687 TI - Evaluation of the MAP1b ELISA for the diagnosis of heartwater in South Africa. PMID- 11193688 TI - Insecticide resistance studies on Blattella germanica (Dictyoptera:Blattellidae) from Cuba. AB - We studied the levels of resistance to seven insecticides: malathion, chlorpyrifos, pirimiphos-methyl, propoxur, cypermethrin, deltamethrin, and lambda cyhalothrin in nine strains of Blattella germanica (Linnaeus, 1717) collected from sites in Santiago de Cuba and Havana City. The strains from Santiago de Cuba, generally had high levels of resistance to malathion, cypermethrin, deltamethrin, and lambda-cyhalothrin, but only low levels of resistance to pirimiphos-methyl, chlorpyrifos, and propoxur. In the strains from Havana City we found a moderate resistance to the organophosphate insecticides, resistance to the pyrethroids (except for three strains that showed susceptibility to lambda cyhalothrin), and susceptibility to the carbamate insecticide (propoxur). PMID- 11193690 TI - The genetic basis for emerging antibiotic resistance in veterinary pathogens. PMID- 11193689 TI - Serological evidence of exposure to Ehrlichia species in dogs in Spain. PMID- 11193691 TI - Association of botulism and tetanus as causative agents of an outbreak of bovine paraplegic mortality in the eastern plains of Colombia. PMID- 11193692 TI - Immune response of naive cattle to successive infestations of Boophilus microplus ticks. PMID- 11193693 TI - Identification of stage-specific genes in Schistosoma mansoni. PMID- 11193694 TI - Homologous and heterologous immune reactions between Venezuelan geographic isolates of Anaplasma marginale. PMID- 11193695 TI - Improving egg production in two indigenous communities through the adaptation of management practices and local knowledge. The results of participative research. AB - Free-ranging poultry (FRP) are known to be efficient in the recycling of residues of agroforestry systems. The objective of this paper is to present the results of participative applied research on the improvement of egg production in two indigenous communities in Costa Rica. This involved a dialectic process of adaptation between indigenous knowledge and introduced management practices. We report an increase in egg production through the use of nests and improved diets. PMID- 11193696 TI - Anaerobic dog bite wound infection. PMID- 11193697 TI - Isolation and partial characterization of the Montecitos strain of Boophilus microplus (Canestrini, 1877) multiresistant to different acaricides. PMID- 11193698 TI - Isolation and morphological characterization of mosquito spirochetes from a Lyme disease endemic area. PMID- 11193699 TI - Proliferation and cytokine profile of T. annulata-infected ovine, caprine, and bovine lymphoblastoid cells. AB - T. annulata, the causative agent of tropical theileriosis in cattle, can also infect ovine and caprine leukocytes in vitro. In vivo studies showed that this parasite causes a mild infection in both these animal species, and in sheep merozoite stage development seems to be inhibited. Since the nature of T. annulata infected caprine and ovine cells is not known, all three cell lines were karyotyped and phenotypically characterized by flow cytometry. They all express mRNA of cytokines IL-1 alpha, IL-1 beta, IL-8, and TNF-alpha, but not of IFN gamma, IL-2, and IL-4. In contrast, IL-6 mRNA was expressed in the cattle cell line only, while mRNA of IL-10 was exclusively produced by the sheep cell line. The observed differences in cytokine mRNA expression may be responsible for the different pathogenesis of T. annulata infection in cattle and sheep. PMID- 11193701 TI - Red meat production and meat losses in Burkina Faso (1987-1997). AB - Based on monthly recorded data collected from 1987 to1997 in all official slaughter houses across the country, this study analyzes the trends of ruminant meat production and importance of meat condemnations by veterinary inspection in Burkina Faso. The average beef production per year is estimated at 6.717.5 + or - 2.969.1 tons, nd for small ruminant meat it is 8,715.5 + or - 4,161.3 tons. During the ten-year period (1987-1997) it appears that a large drop in production (up to 18%) occurred in 1994-1995 consistent with monetary devaluation. The average amount of red meat theoretiacally available for each inhabitant is estimated at 2.14 + or - 0.27 kg per year. Approximately 10 to 16 tons of diseased red meat is condemned every year by veterinary inspection. This is very important for a country where malnutrition and undernutrition is quasi endemic. PMID- 11193700 TI - Safety testing of needle free, jet injection devices to detect contamination with blood and other tissue fluids. AB - Needle free jet injection guns have been used extensively in both veterinary and human health to deliver both vaccine and drugs, but in recent years, concerns have mounted for their potential to transmit blood borne disease agents among consecutive vaccinates. A Ped-O-Jet type jet injection device was used to deliver serial subcutaneous injections of 0.5 mL saline (as a surrogate for vaccine) into calves and pigs, with intervening ejectates collected in vials to represent what the next vaccinate would have received. An enzyme linked immunosorbant assay was developed to detect species specific albumin as a marker for blood, using calibration standards from known dilutions of bovine or porcine blood. Assay sensitivity of 20 pL/mL corresponded to the estimated minimal chimpanzee infectious dose of 10 pL for hepatitis B virus. The methodology and available results for evaluating the safety of jet injector devices are reported. PMID- 11193702 TI - Canine colonization and transmission of Bordetella pertussis. PMID- 11193703 TI - Prevention of disease transmission in primate conservation. PMID- 11193704 TI - Contagious bovine pleuropneumonia. A reassessment of the efficacy of vaccines used in Africa. AB - Contagious bovine pleuropneumonia is a major threat for cattle in Africa. Since 1956 the T1/44 strain has been used as a vaccine, and later on, T1sr, a streptomycin-resistant variant that gives fewer post-vaccinal reactions had been developed. These vaccines are known not to be very efficient but they normally should provide protection for about eight months. However, recent emergency vaccinations, performed in various countries in the southern part of the continent apparently met with failure, casting doubts on the identity as well as the protection afforded by the T1sr strain. A vaccine trial has been designed to reassess the real protection afforded by these vaccines in face of recently isolated pathogenic strains. Great care has been taken to test the original vaccinal strains at a dose corresponding to the minimum requirement by international standards. The test was performed in Cameroon, Kenya, and Namibia as to take into account the genetic diversity that exists among the pathogenic strains. In those conditions, the protection rate at three months varied from 33 to 67%, whatever the strain used, T1/44 or T1sr. These results call for additional research for vaccine development and careful planning of strategies in the fight against CBPP. PMID- 11193705 TI - American canine hepatozoonosis. An emerging disease in the New World. AB - Hepatozoon canis was first described from dogs in 1905 in India and Rhipicephalus sanguineus was identified as the vector. Dogs on the Texas Gulf Coast were recognized in 1978 to have hepatozoonosis, and it was thought that H. canis had entered the New World. Later, it was realized that American canine hepatozoonosis (ACH) is more debilitating than its Old World counterpart, often resulting in death. When the malady and parasite were characterized, a new species, H. americanum, was described, in 1997. Phylogenetic analysis, based on 18S rRNA gene sequence and classical taxonomic features, revealed that the two dog parasites are closely related. Amblyomma maculatum, the Gulf Coast tick (GCT), has been demonstrated to be an excellent vector; nymphal ticks were readily infected and oocysts from newly molted adults were uniformly infectious for dogs. The merogonic cycle of H. americanum in dogs and the sporogonic development in the invertebrate host have been described. ACH is diagnosed primarily by histologic examination of skeletal muscle. Curative therapy is not available, but anti protozoal and anti-inflammatory drugs may prolong life. Naturally infected coyotes have been found in Oklahoma and Texas, and experimental infections have been produced in this canid. Additional effort is needed to determine the vertebrate host range of H. americanum and to define the enzootic cycle of which dogs have become a part; likewise, more work is required to determine whether larval GCTs can acquire infection and transmit it as nymphs. PMID- 11193706 TI - Neosporosis. Aspects of epidemiology and host immune response. AB - Neospora caninum is a recently recognized protozoan parasite which has been described as causing a neuromuscular paralysis in dogs and is emerging as a major cause of bovine infertility and abortion worldwide. The parasite is known to infect a range of warm blooded animals but the disease predominates in dogs and cattle. It is not yet known if N. caninum can infect and cause disease in people. The dog has recently been identified as the definitive host and the parasite may be transmitted through the ingestion of oocysts or congenitally from mother to fetus. N. caninum is known to infect red foxes (Vulpes vulpes) and coyotes (Canis latrans) and the role of wildlife species as reservoirs of infection requires further investigation. Little is known about the range of parasite genotypes within the environment or the variation in virulence between different strains. RAPD-PCR analysis of geographically distinct bovine and canine isolates has revealed little genetic variation. Epidemiological studies from different areas of the world have investigated the importance of N. caninum as an abortifacient agent and longitudinal studies have shown the high rate (approximately 80%) of congenital transmission within infected herds. Information on the rates of repeat abortion due to neosporosis are less well defined however current estimates put this at 5% suggesting that cattle may develop some form of protective immunity against N. caninum-induced abortion. Diagnosis of the disease is based upon detection of the parasite in the tissues, most commonly using immunohistochemistry with additional information provided by serology. However, although positive fetal serology is a strong indicator of exposure to the parasite, care should be taken in the interpretation of maternal serology. As we understand more about the epidemiology of neosporosis we are also better able to interpret the results of diagnostic tests. The mere presence of the parasite does not necessarily infer that this was the primary cause of abortion. CD4+ T-cells, interferon gamma and macrophages have all been found to significantly inhibit multiplication of N. caninum tachyzoites. The nature of a protective immune response and its modulation in the pregnant animal is discussed. PMID- 11193707 TI - A brief history of the Society for Tropical Veterinary Medicine. PMID- 11193708 TI - Catabolic response to stress and injury: implications for regulation. AB - Muscle catabolism is an important component of the metabolic response to stress and injury, including sepsis and burn injury. Muscle wasting and weakness in catabolic patients may adversely affect the outcome in these patients owing to delayed ambulation and involvement of respiratory muscles. An understanding of the regulation of muscle protein breakdown during sepsis and following injury therefore is of great importance from a clinical standpoint and is essential for the development of new therapeutic modalities to prevent protein loss from muscle tissue. Studies in experimental animals and in patients have provided evidence that the myofibrillar proteins actin and myosin are particularly sensitive to the effects of sepsis and injury. (Glucocorticoids, interleukin-1, and tumor necrosis factor participate in the regulation of muscle protein breakdown. Most muscle proteins are degraded by the ubiquitin-proteasome-dependent proteolytic pathway. Because the proteasome does not degrade intact myofibrils, a calcium-dependent Z band disintegration and release of myofilaments from the myofibrils may be an important initial step of muscle breakdown during sepsis and other catabolic conditions. Continued studies to define mechanisms of the catabolic response to stress and injury are important for improving the metabolic care of patients with muscle catabolism. PMID- 11193709 TI - Metabolic assessment. AB - Although no techniques are currently available that meet the needs of nutrition support professionals, the future is promising. This article reviews various methods and techniques used to assess the metabolic and nutritional status of surgical patients. Technologic advances in bioengineering, molecular biology, and physiology are providing exciting new tools that may eventually replace or supplement traditional static indices of metabolic assessment. At the very least, an increased understanding of the cellular abnormalities associated with various diseases will likely change our view of illness and our approaches to nutritional and metabolic intervention. PMID- 11193710 TI - Access routes for nutritional therapy. AB - Enteral nutrition (EN) and total parenteral nutrition (TPN) may provide life sustaining therapy for surgical patients. The duration of nutritional therapy (enteral or parenteral) implies distinct access routes. We review the main aspects related to access routes for nutrient delivery. The enteral route, whenever feasible, is preferred. For EN lasting less than 6 weeks, nasoenteric tubes are the route of choice. Conversely, enterostomy tubes should be used for longer-term enteral feeding and can be placed surgically or with fluoroscopic and endoscopic assistance. The first choice for patients who will not be submitted to laparotomy is percutaneous endoscopic gastrostomy. Postpyloric access, although not consensual, must be considered when there is a high risk of aspiration. For intravenous delivery of nutrients lasting less than 10 days, the peripheral route can be used. However, because of frequent infusion phlebitis, its role is still in discussion. Central venous catheters (CVCs) for TPN delivery may be (1) nonimplantable, percutaneous, nontunneled-used for a few days to 3 to 4 weeks; (2) partially implantable, percutaneous, tunneled-used for longer periods and permanent access; or (3) totally implantable subcutaneous ports-also used for long-term or permanent access. The subclavian vein is usually the insertion site of choice for central venous catheters. Implantable ports are associated with lower rates of septic complications than percutaneous CVCs. The catheter with the least number of necessary lumens should be applied. Central venous nutrient delivery can also be accomplished through peripherally inserted central catheters, which avoid insertion-related risks. PMID- 11193711 TI - Advances in perioperative nutrition: cancer. AB - The role of perioperative nutritional support in the management of cancer patients remains controversial. The benefit of supplemental calories is not the only current issue: in fact, the route of delivery, composition of basic nutrients (carbohydrate, protein, fat), and the role of supplemental additives (arginine, glutamine, omega-3 fatty acids, nucleotides) in improving immune status and ultimate outcome have been the focus of much discussion. Emerging data suggest that the use of supplemental agents is associated with improvement in immune status in these patients, although there is little clear evidence that this improves outcome. Ongoing studies are aimed at defining the group of patients who would most benefit from nutritional interventions during the perioperative period. PMID- 11193712 TI - Short bowel syndrome. AB - The short bowel syndrome is a symptom complex that occurs in adults who have less than 200 cm of jejunum-ileum remaining after intestinal resection. Similar symptoms are observed in infants and children following massive bowel resection or congenital anomalies and in individuals with longer segments of intestine with severe mucosal disease. Initial care should focus on a thorough excision of nonviable bowel, an exact measurement of the remaining viable bowel, placing all intestine in continuity at the initial or subsequent operation, and controlling initial food intake. With time, adaptation of the remnant intestine occurs, and absorptive function may be maximized by enhancing the enteral diet and minimizing parenteral nutrition. Growth factors and specialized nutrients may also enhance this process. Intestinal transplantation should be considered in selected individuals with the short bowel syndrome who fail intestinal rehabilitation protocols. PMID- 11193713 TI - Advances in intravenous lipid emulsions. AB - Over the past decade, our views have considerably evolved with respect to the metabolism of intravenous lipid emulsions and their composition. Substantial progress has been made in understanding the metabolic pathways of emulsion particles and the delivery of their various components (fatty acids and vitamins) to specific tissues or cells. Although soybean long-chain triglycerides represent a valuable source of energy, concerns have been raised about their high content of polyunsaturated fatty acids (mainly n-6 essential fatty acids), which may adversely affect immune functions and antioxidant status. Introduction of medium chain triglycerides or olive oil to lipid emulsions can largely help bypass these disadvantages. Recently, incorporation of n-3 fatty acids in lipid preparations was suggested to have potential application in several chronic and acute diseases because of their ability to reduce inflammatory and thrombotic responses and cell sensitivity to various stimuli. Hence lipid emulsions should no longer be considered only as a means of providing energy substrates; they also modulate key metabolic functions. Such improved knowledge may lead to optimizing the metabolic care of certain patients. PMID- 11193714 TI - Perioperative nutrition and metabolism in pediatric patients. AB - A developing child, with a high metabolic rate and low body stores of nutrients, is susceptible to metabolic disturbances due to surgical stress. For perioperative nutritional care of infants, the distinct physiologic features of their body fluids must be carefully considered. The postoperative metabolic response is the same as that in adults, but in children this response is more rapid. Based on the urinary excretion of 3-methylhistidine in infants, the postoperative degradation of muscle protein is thought to be twice the preoperative level. This transient increase during the early postoperative period was not suppressed by increased amino acid intake, and energy intake was sufficient. To prevent postoperative metabolic complications, the energy intake of glucose or fat should correspond to the patient's requirements, and excess carbohydrate should be avoided. The quantity and quality of the amino acid formula used must be carefully evaluated. PMID- 11193715 TI - Glutamine. AB - Relatively little was known about glutamine metabolism until the 1930s, when Sir Hans Krebs first demonstrated glutamine hydrolysis and biosynthesis in the kidney. Subsequent studies by Rose in 1938 demonstrated that glutamine is a nonessential (dispensable) amino acid, as it can be readily synthesized de novo in virtually all tissues in the body. Because the body has the capacity to synthesize considerable quantities of glutamine, it has been assumed that glutamine is not required in the diet. However, this amino acid becomes quite depleted during the course of a catabolic insult such as injury or infection, indicating that the ability of glutamine production to meet demands during a variety of surgical illnesses is impaired. In states of health, the assumption that glutamine is not required in the diet is probably valid, although it is difficult to test the hypothesis, as glutamine is present in virtually all dietary proteins. Most naturally occurring food proteins contain 4% to 8% of their amino acid residues as glutamine; therefore less than 10 g of dietary glutamine is likely to be consumed daily by the average person. In contrast to this usual dietary availability, studies in stressed patients indicate that considerably larger amounts of glutamine (20-40 g/day) may be necessary to maintain glutamine homeostasis. Thus from a nutritional standpoint, glutamine may be thought of as a drug as well as a nutrient. This paper reviews the physiology and biochemistry of glutamine with an emphasis on its metabolism in surgical illnesses and its role as a conditionally essential amino acid. PMID- 11193716 TI - Growth factors in clinical practice. AB - Growth factors enhance protein synthesis and thus reduce the catabolic response to injury. As a result of bioengineering and new manufacturing techniques several anabolic agents have become available for clinical use and have been evaluated in surgical patients with catabolic illness. Data support the anabolic effects of growth home in such patients, but its expense and possible deleterious effects during the acute phase of illness limit its use to selected patient groups. Insulin-like growth factor-1 has also been studied, but specific indications for its use have not been identified in catabolic patients. Testosterone and derivatives of this hormone exert anabolic effects, but few randomized trials include catabolic surgical patients, and higher doses of some derivative compounds are associated with hepatic dysfunction. Nonetheless, as we move into the future, studies will determine the specific doses for administration of these and other anabolic factors in specific patient groups. Anabolic therapy will shorten the length of therapy and improve the outcome in the future. PMID- 11193717 TI - Creation, evaluation, and continuing assurance of excellence of the certified surgical specialist. AB - A position paper on the subject of certified surgical specialists was published in 1966 under the direction of Professor Charles Wells of Liverpool, England. President John Terblanche of the International Federation of Surgical Colleges brought together leaders in surgical education from four nations (Australia, Japan, South Africa, United States) to update current "state-of-the art" views. Presentations were made at the 38th Congress of the International Society of Surgery, August 18, 1999 in Vienna, Austria. After careful review of the four presentations, it was clear that surgeons all over the world have made great improvements in the many facets of surgical education. Yet the advances remain spotty, with gaps noted when viewed from an international perspective. PMID- 11193719 TI - Lower limb revascularization and free flap transfer for major ischemic tissue loss. AB - The objective of this study was to assess the value of lower limb revascularization and free flap transfer (LLR-FFT) in the management of critical leg ischemia and major tissue loss. A total of 29 consecutive patients with critically ischemic leg and major tissue loss underwent 24 simultaneous and 6 staged LLR-FFT procedures. The main outcome measures were bypass graft patency, free flap viability, leg salvage, patients alive with salvaged leg, and survival. At the 2-year follow-up, the bypass graft patency rate was 85%, secondary free flap viability rate was 82%, and 82% of patients achieved leg salvage and were ambulant. If the success was defined as patients being alive with a salvaged leg, the corresponding rate was 80%. Three patients achieved long-term primary patency and leg salvage despite free flap failure, which occurred during the 30-day postoperative period. Lower extremity revascularization plus free flap coverage of large ischemic lesions is valuable in achieving long-term leg salvage. Because revascularization and conventional management of major tissue loss alone can be effective in the management of a small number of cases, staged LLR-FFT is indicated, when appropriate, for better selection of patients undergoing such an aggressive and demanding treatment. PMID- 11193718 TI - Role of malignancy and preoperative embolization in the management of carotid body tumors. AB - The purpose of this retrospective study is to present our approach to the management of patients with carotid body tumors (CBTs), emphasizing the role of malignancy and preoperative embolization. Between 1975 and 1998 a series of 18 patients with CBTs were treated, and 16 of them underwent successful excision of the tumor. According to the Shamblin classification, six of the tumors were type I, six type II, and six type III. In three of these patients (two with type II tumors and one with type III) in whom preoperative embolization had been performed, mean intraoperative blood loss was 400 ml, whereas in the remaining 13 cases this loss was 700 ml. Two patients with intracranial tumor spread underwent only radiotherapy. Neither postoperative deaths nor strokes occurred. Temporary cranial nerve injury occurred in four cases (25%). Local lymph node invasion was found in two patients, establishing the diagnosis of malignancy. One of these patients developed distal metastases 3 years after the operation and was treated with radiotherapy and octreotide. Follow-up ranging from 30 months to 23 years (mean 5 years) revealed no local recurrence except for the two patients who were treated with radiotherapy only. In conclusion, surgical excision remains the treatment of choice for CBTs and can be performed without major risks and with low morbidity and mortality. Preoperative embolization is helpful by diminishing intraoperative bleeding, and malignancy, though rare justifies early management. PMID- 11193720 TI - Remaining small bowel length: association with catheter sepsis in patients receiving home total parenteral nutrition: evidence of bacterial translocation. AB - Patients with short bowel syndrome (SBS) receiving total parenteral nutrition (TPN) have a high incidence of catheter-related sepsis, one of its major complications. The aim of this study was to correlate the length of remaining small bowel (RSB) with septic episodes related to the central venous catheter in a group of patients with severe SBS with home TPN. The length of the RSB (<50 cm or > or = 50 cm) was related to the frequency of catheter sepsis, time until the first episode, and the agents responsible in eight SBS patients receiving home TPN. There were 13 episodes of catheter infection (0.88 per patient-year). The group with a shorter RSB length (five patients) presented 1.3 to 2.76 infections/year and 2 to 9 months until the first episode, compared to 0 to 0.75 infections/ year (p = 0.0357) and 11 to 65 months until the first episode (p = 0.0332) in the group with the longer RSB. In the first group, the agents isolated were Enterobacteriae (Enterobacter sp., Klebsiella sp., Pseudomonas sp., and Proteus sp.) in eight episodes and Candida sp. in one. In the latter sepsis was caused by Staphylococcus sp. in three episodes and Pseudomonas sp. in one. Therefore patients with remaining small bowel shorter than 50 cm have a higher frequency of catheter-related sepsis, particularly by enteric microorganisms. This might be an evidence of the occurrence of bacterial translocation and its role in the pathogenesis of catheter-related sepsis in patients with an extremely short RSB receiving home TPN. PMID- 11193721 TI - Relation between effective utilization of exogenous fat emulsion as energy substrate and oxygen metabolism after surgery. AB - It is known that fat oxidation is increased in patients who have sustained surgical stress, but it is not clear whether fat emulsion should be administered during the early postoperative period. The aim of this study was to evaluate the utilization of exogenous fat emulsion after major surgery. Total parenteral nutrition composed of glucose/amino acids or glucose/amino acids/fat was administered for 6 days to 18 patients who had undergone esophagectomy. The caloric intake was significantly less than the resting energy expenditure (REE), and there was no difference in substrate utilization in either group up to postoperative day (POD) 2. After POD 4, fat utilization was significantly increased in the fat group. The total ketone body concentration was higher in the fat group than in the glucose group on POD 1 and 2. The arterial ketone body ratio (AKBR), which reflects the rate of turnover of the Krebs cycle, was positively correlated with the caloric intake/REE ratio. It was negatively correlated with the oxygen delivery index, oxygen consumption, and lactate concentration between POD 0 and POD 2. The lactate concentration was decreased and the AKBR was increased by POD 4. Fat emulsion was effectively utilized as energy substrate after POD 4, after the relative tissue hypoxia had improved and the AKBR had increased. The utilization of exogenous fat emulsion was closely related to deficient caloric intake and oxygen metabolism. PMID- 11193722 TI - Evaluation of the Maruyama computer program accuracy for preoperative estimation of lymph node metastases from gastric cancer. AB - Controversy still exists about the optimal lymph node (LN) dissection for potentially curable gastric cancer. For rational LN dissection it is important to know the incidence of metastasis at each LN station. For this purpose a computer program was developed using data from 4302 primary gastric cancers treated at the National Cancer Center Hospital in Tokyo between 1969 and 1989. To evaluate the accuracy of the computer program, the differences between the individual reports generated by the computer and the stored data were investigated in 282 Italian patients submitted to curative gastrectomy and D2 or more extended LN dissections for gastric cancer. Receiver operating characteristic (ROC) analysis was used to assess the sensitivity and specificity of the program for predicting LN metastases in each of the 16 regional LN stations. The computer program showed good predictive ability for LN metastases in most of the 16 LN stations, as the areas under the curve ranged from 0.741 (station 15) to 0.944 (station 8), with a mean of 0.856. A critical cutoff point of 18% of the program's expected percentage was the value maximizing the validity of the prediction. Using an "absolute" cutoff point of 0%, the overall rate of false-negative (FN) predictions in 176 N+ patients was 11.9%; of these, 11 (6.2%) were absolute FNs, in which the program totally failed to estimate LN metastases; the remaining 10 cases (5.7%) were relative FNs because the specific prediction was positive for a different depth of stomach invasion. The low number of D3/D4 lymph-adenectomies in the historical database may affect the low estimate of metastases to N3/N4 nodes generated by the program. Based on these data, the program predicts with good accuracy the extent of LN metastases from gastric cancer, but it is not recommended for directing the surgeon to perform more extensive lymphadenectomy. PMID- 11193723 TI - Risk factors for recurrence after resection of hepatitis C virus-related hepatocellular carcinoma. AB - Although there have been many studies of the risk factors for recurrence after resection of hepatocellular carcinoma (HCC), the subjects were patients with various viral status in the previous studies, and hepatitis C viremia has not been evaluated. We investigated risk factors, including hepatic C viremia and histologic findings of noncancerous hepatic tissue, for recurrence after resection of hepatitis C virus (HCV)-related HCC. A total of 223 patients who underwent liver resection for HCV-related HCC were studied. HCV viremia, laboratory data, degree of HCC malignancy, histologic findings in noncancerous hepatic tissue, preoperative interferon therapy, and operative methods were evaluated for recurrence risk by univariate and multivariate analyses. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin, and the proportion of patients with a high histologic activity score (mild to severe active hepatitis) were significantly higher in patients with HCV viremia than in those without viremia. Serum albumin was significantly lower in patients with HCV viremia. By univariate analysis, older age (> 65 years old), HCV viremia, elevated AST (> 40 IU/L) and ALT (> 45 IU/L), large tumors (> 40 mm), multiple HCCs, moderately or poorly differentiated HCC, portal invasion, mild to severe active hepatitis, and lack of preoperative interferon therapy were risk factors for recurrence. Multivariate analysis showed that older age, HCV viremia, high AST, multiple HCCs, and portal invasion were independent risk factors. For HCV-related HCCs, not only the degree of malignancy of the HCC but also HCV viremia and active hepatitis are risk factors for recurrence. PMID- 11193724 TI - Additional hepatocellular carcinomas undetectable before surgery. AB - The presence of small additional hepatocellular carcinomas (HCCs) undetectable before hepatic resection is a crucial topic for hepatic surgeons. We assessed the incidence of pathologically diagnosed multiple HCCs in 267 patients who underwent hepatic resection for HCC. Ninety-five additional HCC nodules were detected in 72 of the patients (27%). The survival rate of these 72 patients was significant worse than for the 195 with single nodular HCC (p = 0.0013). Twenty-one (22%) were detected before surgery, 29 (31%) during surgery, and 45 (47%) on pathologic examination after surgery. The mean nodule diameters for each group were 2.1, 1.0, and 0.9 cm, respectively (p < 0.0001). None of the 21 nodules detected before surgery was well differentiated, whereas 30 of the 74 nodules in the other two groups were well-differentiated. Although the mean nodule diameter of the well-differentiated HCC group was the smallest, there was no significant difference among the three groups assigned according to tumor differentiation (p = 0.2355). Altogether, 9 of 16 patients with additional nodules detected before surgery (56%) and 49 of 59 with additional nodules detected during or after surgery (88%) had cirrhosis of the liver. The odds ratio for detecting a new HCC nodule during or after surgery in the presence of cirrhosis was 5.444 (p = 0.0087). Improvement in the detection of small additional HCC nodules before and during surgery and meticulous follow-up after surgery are necessary for patients with cirrhosis. For patients without cirrhosis, surgical treatment may be performed according to the results of preoperative imaging studies. PMID- 11193725 TI - Upper airway obstruction in patients with goiter studies by flow volume loops and effect of thyroidectomy. AB - The patient with goiter and his or her physician frequently overlook symptoms of upper respiratory obstruction. Conventional radiology is the accepted method for detecting upper airway obstruction in these patients. Flow volume loops provide additional information on airflow dynamics. Twenty-five patients of goiter undergoing surgery were evaluated for upper airway obstruction by symptomatology, conventional radiology, and flow volume loops. Flow volume loops were repeated 1 month after surgery. Ten (40%) patients had mild symptoms on direct questioning. Tracheal deviation, compression, or both were noted in eight (32%) patients on radiology. Flow volume loops detected upper airway obstruction in 15 (60%) patients. Surgery resulted in normalization of all preoperative abnormal curves. The flow volume loop is a simple noninvasive method for detecting upper airway obstruction in patients with goiter. Abnormal upper airway dynamics are present in more patients with goiter than previously recognized, and relief of this obstruction should be an important aspect of thyroid surgery. PMID- 11193726 TI - Preoperative localization of parathyroid adenoma in patients with concomitant thyroid nodular disease. AB - We have previously demonstrated the role of high-resolution ultrasonography (US) in preoperative localization of parathyroid adenoma in patients with primary hyperparathyroidism (PHPT) and no thyroid abnormalities. The present study prospectively evaluated the possible additional value of 99mTc-sestamibi (MIBI) in patients with PHPT and concomitant multinodular thyroid disease (MND). Patients with PHPT underwent US and MIBI scintigraphy prior to neck exploration. Imaging data were correlated with the site and pathology of the parathyroid tissue removed and were analyzed separately for patients with MND and those with a normal thyroid gland. Among 77 patients with a solitary parathyroid adenoma at surgery, 40 had concomitant MND, whereas 37 patients had no morphologic changes in the thyroid gland, on US or at surgery. Prior to surgery, MIBI scintigraphy depicted 58 of the 77 adenomas (75%) and US localized 51 (66%): the combined sensitivity was 87% (67/77). Among the 37 patients with no thyroid nodules, MIBI located 29 (78%) and US identified 30 (81%) of the adenomas; the combined sensitivity was 89%. In the 40 patients with MND, MIBI identified 29 adenomas (73%) and US localized only 53% (21/40); the combined sensitivity was 85%. Overall, the positive predictive value (PPV) of MIBI for detecting a solitary parathyroid adenoma was 94%, for US it was 88%, and with the two tests combined it was 97%. In patients with no thyroid abnormalities, the PPV of MIBI and US was 97%, but it decreased to 91% and 78%, respectively, in patients with MND. Two patients with false-positive findings on both MIBI and US had associated thyroid disease. Hence MIBI scintigraphy contributes to localization of a solitary parathyroid adenoma mainly in patients with concomitant MND. The combined MIBI and US modalities result in sparing these patients bilateral neck exploration. PMID- 11193727 TI - Pancreastatin plasma levels in patients with primary hyperparathyroidism. AB - Pancreastatin, a C-terminally amidated peptide derived from chromogranin A, is known to inhibit insulin secretion, pancreatic enzyme release, and gastric acid secretion. It also inhibits parathyroid hormone (PTH) secretion in animals. The physiologic and clinical relevance of pancreastatin in humans, however, is not known. Because pancreastatin has been found in parathyroid adenomas, we investigated the plasma levels in patients with primary hyperparathyroidism (pHPT). Thirteen patients operated on for solitary parathyroid adenoma were investigated. Plasma levels of pancreastatin and serum levels of ionized calcium and intact PTH were measured before and 6 weeks after operation. In 10 patients the levels were also monitored before and 60 minutes after adenoma excision. The adenomas were investigated for pancreastatin immunoreactivity by immunocytochemistry. The median weight of the excised parathyroid adenoma was 0.64 g (range 0.07-2.00 g). Cells displaying pancreastatin immunoreactivity were present in all adenomas examined and varied in number and immunostaining intensity among and within the adenomas. Intraoperatively, after adenoma excision the levels of PTH and pancreastatin declined (p < 0.01), whereas the levels of ionized calcium did not change (p = 0.96). At the 6-week follow-up the levels of ionized calcium and PTH had decreased compared to the preoperative levels (p < 0.01), and all patients were normocalcemic. In contrast, the pancreastatin levels were not changed (14.5 +/- 6.1 pmol/L preoperatively vs. 12.8 +/- 11.2 pmol/L 6 weeks postoperatively; p = 0.12). In patients with pHPT, pancreastatin is likely to be produced by the parathyroid adenoma. The changes in pancreastatin levels immediately after surgery warrant further investigation. PMID- 11193728 TI - Comparison of coagulation parameters for healthy subjects and Behcet disease patients with and without vascular involvement. AB - Behcet disease (BD) is an inflammatory illness that may attack several systems. Vascular involvement with thrombosis is one of the basic characteristics of this disease. The etiology of thrombosis tendency in BD has not been understood well. In this study, the role of primary coagulation parameters in patients with BD who have thromboembolic events was evaluated. In addition, the relation between the clinical activity of the disease and these parameters was compared. A total of 96 patients with a diagnosis of BD were studied at Ankara University, Medical School, Department of General Surgery and Behcet Center. BD patients were separated into two groups with respect to vascular involvement. Group A contained 22 patients with vascular attacks, and group B contained 74 patients without vascular attacks. In addition, 25 healthy persons comprised the control group (group C). The coagulation parameters assessed included protein C, protein S, antithrombin III activity, fibrinogen level, prothrombin time (PT), and partial thromboplastin time (PTT). There were no differences among the three groups with respect to protein C, protein S, fibrinogen, PT, and PTT values (p > 0.05). The antithrombin III value was found to be high in BD patients compared to those in the control group (p = 0.011). There was no difference regarding the antithrombin III value between BD patients with or without vascular attacks (p = 0.954). There was no correlation between the activity of disease and coagulation parameters (p > 0.05), but a positive correlation was seen between the duration of illness and vascular involvement. Fifty percent of patients who had had BD more than 8 years had vascular involvement (p = 0.002). We could not determine a specific pathology in relation to coagulation parameters that could explain the etiology of thrombosis in patients with BD. The elevated antithrombin III levels in patients with BD (compared to controls) may be due to a compensatory defense mechanism against increased procoagulant activity. There was a correlation between the duration of illness and vascular involvement. PMID- 11193729 TI - II. Vinzenz Czerny (1842-1915): grand seigneur of oncologic surgery--life, influence, and work of the Second Congress President of the ISS/SIC. International Society of Surgery/Societe Internationale de Chirurgie. AB - Vinzenz Czerny, chairman and professor of surgery in Freiburg im Breisgau and in Heidelberg, Germany, is the typical example of a prominent surgeon with an elegant technique, who was also a keen observer and scientist at the turn of the nineteenth into the early twentieth century. Starting his career in Vienna, Austria, he can be looked upon as the most important disciple of Theodor Billroth. Whereas Billroth may be regarded as the father of modern gastrointestinal surgery, Czerny can be considered the father of modern surgery for intestinal malignancies and multimodal treatment. The early history of visceral cancer therapy is linked with his career. He became a surgeon of the highest rank, with great clinical skill, rare judgment, and vision who contributed essentially to the development of modern surgery. From his early education he maintained a lifelong affection for the natural sciences and was an excellent physiologist and pathologist. During his professional life he successfully built up a well deserved reputation for general and cancer surgery and for the introduction of radio- and chemotherapy into the treatment of tumors. Czerny founded and chaired the first experimental Institute for Cancer Research in Germany. Two years later, in 1908, he presided at the 2nd Congress of the International Society of Surgery/Societe Internationale de Chirurgie (ISS/SIC) in Brussels, a congress that was almost entirely devoted to the etiology of visceral cancer and the progress and achievements of its treatment. Czerny left a clear legacy of opinion and methods on which the modern era of surgical cancer treatment is based. PMID- 11193730 TI - Plant Virus Epidemiology: Challenges for the twenty-first century. 11-16 April 1999. Conference proceedings. PMID- 11193731 TI - An extremely interesting conference. PMID- 11193732 TI - Emerging new biotechnologies and the patent attorneys' struggle to best protect them. PMID- 11193733 TI - Biomonitoring, ecoextrapolation and then bioremediation for ecorestoration? PMID- 11193734 TI - Chloroplast genetic engineering. PMID- 11193735 TI - Tubular carcinoma of the breast: a histologic subtype indicative of breast conserving therapy. AB - We reviewed the clinical and pathologic features of pure tubular carcinoma of the breast with particular emphasis on the reported risk factors associated with local recurrences and survival following breast-conserving therapy. Of 1653 cases of invasive breast cancer, 12 (0.7%) were identified as pure tubular carcinoma. Clinical/pathologic features of pure tubular carcinoma were compared with those of T1 invasive carcinoma of all other histologic types (T1 IC). Of the 12 patients with pure tubular carcinoma (median tumor diameter 1.4 cm; range 0.5-3.0 cm), a multicentric association was identified in one patient while a multifocal association was seen in two. One patient had nodal metastatic disease out of the ten who underwent axillary dissection. No lymphatic vessel invasion was identified in any tumors (P < 0.1 vs T1 IC). In addition, extensive intraductal spread was not present in any tumors (P < 0.05 vs T1 IC). This study shows that patients with pure tubular carcinoma are appropriate candidates for breast conserving therapy based on the clinical/ pathologic features. When a multifocal association is suspected preoperatively, either a wide local excision or a quadrantectomy which includes other lesions is thus recommended. PMID- 11193736 TI - The prognosis of patients with non-small cell lung cancer found to have carcinomatous pleuritis at thoracotomy. AB - Non-small cell lung cancer with carcinomatous pleuritis is considered to be a contraindication of surgical resection. The objective of this study was to clarify the prognosis of patients with non-small cell lung cancer in whom carcinomatous pleuritis was found at thoracotomy. A questionnaire survey on the survival of patients with carcinomatous pleuritis found at thoracotomy between January 1985 and December 1994 was conducted by the Japan Clinical Oncology Group. According to the data collected from 21 hospitals, 8813 patients with non small cell lung cancer underwent thoracotomy, 284 (3.2%) of whom were found to have carcinomatous pleuritis. Information on survival was available for 227 of these patients, 34 (15%) of whom underwent thoracotomy alone without resection, whereas 193 (85%) underwent surgical resection. Of the 193 resected patients, 155 had no macroscopical residual tumor apart from the carcinomatous pleuritis. The 5 year survival rate was 14%. According to a univariate analysis, female sex, the presence of adenocarcinoma, a tumor size of less than 3.0 cm, no clinical lymph node metastasis, and no macroscopical residual tumor had a significantly favorable impact on survival. A multivariate analysis revealed that the extent of clinical lymph node metastasis (P = 0.006), histology (P = 0.028), and the absence or presence of a macroscopic residual tumor after the operation (P = 0.045) were predominant prognostic factors. The 5-year survival rate of 83 patients with three positive variables was 24%. The prognosis of patients with adenocarcinoma found to have carcinomatous pleuritis at thoracotomy was not necessarily unfavorable if there was no clinically detected lymph node metastasis and no residual tumor apart from the carcinomatous pleuritis. PMID- 11193737 TI - A phase II trial of a new 5-fluorouracil derivative, BOF-A2 (Emitefur), for patients with advanced gastric cancer. AB - The antineoplastic effects of BOF-A2 (Emitefur), a 5-fluorouracil (5-FU) derivative, in capsule form were assessed in patients with advanced gastric cancer, in a multicenter late phase II study and at 11 different hospitals. The patients were scheduled to receive a minimum of two courses of BOF-A2 orally, with each course of BOF-A2 consisting of 200 mg twice daily for 2 weeks followed by a withdrawal period of 2 weeks. Of the 24 patients entered into the study, the clinical response was able to be evaluated in 21 cases and the toxicity was determined in 23 cases. Eleven (45.8%) patients had been treated previously with other anticancer drugs. There was a 38.1% (8/21) response rate (95% confidence interval 17.3-58.9) with 1 (4.8%) complete response (CR) and 7 (33.3%) partial responses (PR), and these responses continued for over 4 months. In particular, the response rate for the primary lesion was 33.3% (3/9). No change (NC) in the disease was observed in 5 (23.8%) patients, and in 8 (38.1%) the disease progressed (PD). At the time of analysis, the median survival of the responders was 13 months, while that of the NC group was 7 months and that of the PD group was 2 months. The major adverse events consisted of gastrointestinal symptoms, myelosuppression, and skin symptoms, while toxicities of grade 3 or more occurred in 26.1% (6/23). These toxicities all resolved within 1-37 days after discontinuing the drug treatment. Based on the above findings, BOF-A2 is considered to be a promising anticancer drug for patients with advanced gastric cancer. PMID- 11193738 TI - Lymph node metastasis-related carbohydrate epitopes of gastric cancer with submucosal invasion. AB - This study was conducted to examine the lymph node metastasis-related carbohydrate epitopes of cancer cells in primary lesions of gastric cancer with submucosal invasion (sm gastric cancer). A total of 118 formalin-fixed and paraffin-embedded surgical specimens were studied. Carbohydrate epitopes were detected histochemically using 17 kinds of biotin-labeled lectins and three kinds of monoclonal antibodies (mAbs) against Thomsen-Friedenreich antigen (HB-T1), Tn (HB-Tn1), and sialyl Tn antigens (HB-STn1). The node-positive group showed significantly lower reactivities with Ricinus communis I (RCA-I), Lotus tetragonolobus (Lotus), Triticum vulgaris (WGA), and Concanavalia ensiformis (ConA), and higher reactivities with HB-STn1. When sm gastric cancer was classified into differentiated and undifferentiated types, lower reactivities with RCA-I and ConA were observed in the differentiated type cancers, whereas lower reactivities with Lotus, WGA, and higher reactivity with HB-STn1 were observed in the undifferentiated type cancers. Nodal status was able to be predicted with high precision by a combination of these carbohydrates and histological subtypes. Since neuraminidase treatment rarely changed the reactivity of cancer cells with these lectins, we conclude that the loss of certain kinds of carbohydrates that are restricted by histological subtypes is related to lymph node metastasis in sm gastric cancer. PMID- 11193739 TI - Immunocytochemical analysis of cellular infiltrates in human appendicitis. AB - This study was conducted to determine the immunologic cellular composition in human appendicitis and its association with the development of perforated appendicitis. Appendiceal specimens from 27 patients with acute appendicitis were immunostained to detect lymphocyte surface markers. Moreover, the lymphocyte surface markers of peripheral blood were analyzed by laser flow cytometry in 12 patients. Helper T lymphocytes (CD4) were present in all the patients, while B lymphocytes (CD19), natural killer (NK) cells (CD56), and cytotoxic T lymphocytes (CD8) were present in 7 (70%), 10 (100%), and 9 patients (90%) with perforated appendicitis, and in 12 (63.2%), 10 (58.8%), and 6 (54.5%) patients without perforation, respectively. There were significant differences between the patients with a perforated appendix and those without perforation, in the positivity rate for CD8 and CD56 cells (P < 0.05). The number of cells positive for CD56, being NK cells, in the blood from the patients with perforation was significantly lower than that in the blood from those without perforation (P < 0.05). The infiltration of a greater number of cytotoxic T lymphocytes and NK cells was observed in the appendices from patients with perforated appendicitis than in those from patients with nonperforated appendicitis. PMID- 11193740 TI - The effect of upper dorsal thoracoscopic sympathectomy on the total amount of body perspiration. AB - Thoracoscopic T2-T3 sympathectomy is the treatment of choice for primary palmar hyperhidrosis (PPH); however, compensatory hyperhidrosis (CH) is a disturbing sequela of this operation, the mechanism of which is poorly understood. This study was conducted to evaluate the effect of heat stress on total body perspiration after thoracoscopic T2-T3 sympathectomy, and determine its correlation with CH. A total of 17 patients with PPH who underwent bilateral T2 T3 sympathectomy were subjected to heat stress induced by a 10-min sauna bath (ambient temperature 70 degrees C), 1 day before and 1 month after surgery. The naked body weight was recorded before and immediately following the sauna bath, and the patients were followed up to assess whether CH had developed and the degree of its severity. Postoperatively, the amount of perspiration increased in 13 patients and decreased in 1. The amount of perspiration induced by the sauna bath ranged from 60 to 480 g, with a mean value of 185.29 +/- 125.80 g, before the operation, and from 60 to 540 g, with a mean value of 265.88 +/- 154.05 g, after the operation (P = 0.0113). There was no correlation between the degree of alteration in total body perspiration and the development of CH. Performing thoracoscopic T2-T3 sympathectomy for PPH affects the total body sweating response to heat; however, the development of CH does not correlate with this alteration. PMID- 11193741 TI - The effect of immunosuppression on aortic dilatation in a rat aneurysm model. AB - This study was conducted to investigate whether systemic immunosuppression attenuated aortic dilatation in a rat aneurysm model. Sprague-Dawley rats were subjected to elastase infusion of the infrarenal aorta and divided into two groups of 12 rats each. The immunosuppression group (group 1) was given subcutaneous injections of cyclosporine A (5 mg/kg per day), azathioprine (2 mg/kg per day), and methylprednisolone (2 mg/kg per day) from the operative day until postoperative day (POD) 6. An additional subcutaneus injection of cyclophosphamide 30 mg/kg was also given on the operative day. The control group (group 2) was given subcutaneous injections of saline. Relaparotomy was performed on POD 7. After measurement of the aortic diameter, aortography and ultrasonography were performed in three rats from each group, following which the aortas were excised for histologic examination. The aortic diameter was significantly smaller in group 1 (2.58 +/- 0.37 mm) than in group 2 (6.21 +/- 1.74 mm) (P < 0.01) and the aortic lumen was slightly dilated in group 1, whereas it was spherically dilated in group 2. Total loss of elastic tissue was seen in both groups. Inflammatory cell infiltration and collagen fiber fragmentation were noted in group 2, whereas very little inflammatory cell infiltration and well preserved collagen fibers were seen in group 1. These findings showed that immunosuppression attenuates aortic dilatation, partly by preserving the collagen fibers, in this rat aneurysm model. PMID- 11193742 TI - Therapeutic effect of TNP-470 on spontaneous liver metastasis of colon tumors in the rabbit. AB - Even though angiogenesis inhibitor is thought to be one of the promising agents in tumor dormancy therapy, its optimal administration is still unknown. Therefore, the efficient protocol using TNP-470 was examined regarding its treatment affect against spontaneous liver metastases of colon tumors in the rabbit. A spontaneous liver metastases model was established in the rabbit by the inoculation of VX-2 tumors into the subserosal space of the colon. The therapeutic effect of TNP-470 was then investigated by monitoring both the number of metastatic nodules in the liver and the microvessel density (MVD) in the tumor by immunohistochemical staining using anti-CD31 monoclonal antibody. TNP-470 did not show any effect on the primary tumor. It was able to reduce the metastatic spread to liver when it was administered at the microscopic metastatic stage. Treatment at this stage, however, was not able to sufficiently control the disease. These results indicated that TNP-470 could efficiently cause the tumor to enter into a dormant state by inhibiting angiogenesis when it was used at the initial stage of the metastatic process in the liver. Regarding its clinical application, TNP-470 might be useful for preventing the metachronous liver metastases of colorectal cancer when it is administered as adjuvant therapy after curative surgery. PMID- 11193743 TI - Rhabdomyosarcoma presenting as an anterior cervical mass in an adult: report of a case. AB - We report herein the case of a 61-year-old man who was referred to our hospital for treatment of a rapidly growing tumor in the right anterior cervical region. A 13 x 14 x 15 cm mass was palpated on physical examination. Computed tomography (CT) findings indicated a thyroid tumor, but cytology results suggested rhabdomyosarcoma. A tumor, measuring 9.3 x 7.2 x 5.2 cm and weighing 220 g, was resected and histopathological examination confirmed a diagnosis of rhabdomyosarcoma. Cervical rhabdomyosarcoma is rarely found in adults. PMID- 11193744 TI - Reexpansion pulmonary edema due to high-frequency jet ventilation: report of a case. AB - Barotrauma is well known to be a relatively common complication of high-frequency jet ventilation (HFJV); however, the occurrence of reexpansion pulmonary edema (REPE) is extremely rare. We report herein a case of REPE caused by difficulties encountered with anesthesia using HFJV during video-assisted thoracic surgery (VATS) for a spontaneous pneumothorax. We believe the rapid increase in pressure in the lung after degassing for VATS resulted in REPE as well as typical barotrauma. PMID- 11193745 TI - Left ventricular myxoma: report of a case. AB - Although recent advances in echocardiography have made it easier to detect cardiac tumors, left ventricular myxomas are still rare and often not found until the patient presents with a history of syncopal episodes or systemic embolization. Left ventricular myxomas are usually benign and curable; however, unreliable excision of the myxoma due to poor visualization of the left ventricular cavity can result in recurrence. To prevent recurrence, it is necessary to select the most appropriate surgical approach to excise the myxoma completely. We report herein the case of a patient in whom surgical excision of a left ventricular myxoma arising from the posterior wall of the left ventricle was successfully performed. PMID- 11193746 TI - Surgical treatment of a sigmoid volvulus associated with megacolon: report of a case. AB - Sigmoid volvulus occurring concomitantly with megacolon is an uncommon cause of bowel obstruction, and various approaches to treatment have been proposed. We report herein a case of sigmoid volvulus with megacolon that was successfully treated by elective surgery following endoscopic reduction during the same hospital stay. A 70-year-old woman was admitted to our hospital with abdominal pain, distension, and severe constipation. Physical examination, plain abdominal X-ray, and barium enema confirmed a sigmoid volvulus and further examinations revealed concomitant megacolon. An elective sigmoid colectomy was performed following successful endoscopic decompression. The postoperative course was uneventful and there was no residual colonic dysmotility. Histologically, no aganglionic tissue was observed in the resected specimen. PMID- 11193747 TI - Metastasis to the forearm skeletal muscle from an adenocarcinoma of the colon: report of a case. AB - While the liver and lung are primary targets for distant metastasis from colorectal carcinoma, metastasis in other distant sites is rarely found. We report herein an unusual case of metastasis to the skeletal muscle of the right forearm from an adenocarcinoma of the transverse colon. A 60-year-old man was originally admitted to our hospital for surgical treatment of an intestinal obstruction caused by a transverse colon carcinoma. Transverse colon resection along with lymph node dissection was performed and no evidence of distant metastatic foci was found. Angiography-enhanced computed tomography scanning done 14 months after the first operation revealed multiple hepatic metastases which were resected. A metastasis was subsequently detected in the right extensor carpi ulnaris muscle 2 years after the primary resection, and a major part of the right extensor carpi ulnaris and the extensor digiti minimi muscle were resected, warranting a sufficient margin of 5 cm of normal tissue from the tumor. Reattachment of the residual muscles into the ulna was performed. Metastases to bone and/or soft tissues from colorectal carcinomas are extremely rare and to our knowledge, only eight other cases have been reported in the world literature. This low incidence may be related to the anatomical characteristics and/or the biochemical environment of the skeletal muscle, but it is also possible that the true incidence is underestimated. Recent improvements in interventional radiological procedures may facilitate a diagnosis of skeletal muscle metastasis being made more frequently. PMID- 11193748 TI - Membranous glomerulonephritis associated with diffuse malignant pleural mesothelioma: report of a case. AB - Membranous glomerulonephritis is associated with a variety of malignant neoplasms. However, an association between membranous glomerulonephritis and pleural mesothelioma is very rare. We report herein a case of pleural mesothelioma associated with membranous glomerulonephritis. A 52-year-old man with severe proteinuria was diagnosed to have diffuse malignant pleural mesothelioma. A left extrapleural pneumonectomy was thus performed. The proteinuria resolved postoperatively. However, 6 months postoperatively, the proteinuria recurred. A renal biopsy revealed membranous glomerulonephritis. Simultaneously, a recurrence of the mesothelioma in the left pleural cavity was confirmed. Although rare, membranous glomerulonephritis appears to be one type of paraneoplastic syndrome associated with malignant pleural mesothelioma. PMID- 11193749 TI - Discovery and perspectives from the blastokinin era. AB - The events and rationalizations that led to one discovery of the rabbit uterine protein, then called blastokinin, are narrated in historical perspective and related to the independent discovery of the same protein, named uteroglobin. The period when the name "blastokinin" remained in partial use, roughly from the original publication in 1967 until the early 1980s, is considered here as the blastokinin era. Subsequent perspectives, originating from the era, are presented on the hormonal regulation of blastokinin, as well as its distribution, biological function, and potential relationships with other entities that exist coincidentally. PMID- 11193750 TI - Crystal structure analysis of recombinant human uteroglobin and molecular modeling of ligand binding. AB - Uteroglobin, a steroid-inducible, cytokine-like, secreted protein with immunomodulatory properties, has been reported to bind progesterone, polychlorinated biphenyls (PCB), and retinol. Structural studies may delineate whether binding of ligands is a likely physiological function of human uteroglobin (hUG). We report a refined crystal structure of uncomplexed recombinant hUG (rhUG) at 2.5-A resolution and the results of our molecular modeling studies of ligand binding to the central hydrophobic cavity of rhUG. The crystal structure of rhUG is very similar to that of reported crystal structures of uteroglobins. Using molecular modeling techniques, the three ligands--PCB, progesterone, and retinol--were docked into the hydrophobic cavity of the dimer structure of rhUG. We undocked the progesterone ligand by pulling the ligand from the cavity into the solvent. From our modeling and undocking studies of progesterone, it is clear that these types of hydrophobic ligands could slip into the cavity between helix-3 and helix-3' of the dimer instead of between helix-1 and helix-4 of the monomer, as proposed earlier. Our results suggest that at least one of the physiological functions of UG is to bind to hydrophobic ligands, such as progesterone and retinol. PMID- 11193751 TI - Antiflammins. Bioactive peptides derived from uteroglobin. AB - Uteroglobin/Clara cell 10-kDa protein (UG/CC10) is a hormonally regulated small secretory protein that has a variety of in vitro and in vivo pharmacological effects. These include a potent anti-inflammatory activity and inhibitory effects on neutrophil migration, thrombin-induced platelet aggregation, in vitro chemoinvasion, as well as "tumor suppressor"-like effects and other properties. Several mechanisms of action have been proposed for these effects. Pharmacological properties suggest that UG itself or substances derived from it may be used as experimental drugs for several indications. The group of oligopeptides collectively known as "antiflammins" (AFs) were originally described in 1988. Their design was derived from the region of highest sequence similarity between UG and another group of proteins with anti-inflammatory properties, the lipocortins or annexins. Nanomolar concentrations of these peptides can reproduce several of the pharmacological activities of UG, including its in vivo anti-inflammatory effects and inhibition of platelet aggregation. The AFs have been safely and effectively used to suppress inflammation and fibrosis in several animal models. Progress in clarifying the mechanism of action of the AFs may facilitate the structure-based design of a novel class of potent anti inflammatory, antichemotactic drugs. PMID- 11193752 TI - Therapeutic applications of antiflammin peptides in experimental ocular inflammation. AB - Antiflammins are synthetic peptides derived from the region of highest local similarity between uteroglobulin and lipocortin. These peptides have shown anti inflammatory activity on carrageenan-induced rat footpad edema. They are potent inhibitors for phospholipase A2 activation both in vitro and in vivo. Previously, we have demonstrated the effectiveness of topical antiflammins in suppressing acute ocular inflammation and allergic response in rodent endotoxin-induced uveitis and murine allergic conjunctivitis. The mechanisms by which antiflammins protect against inflammation and allergy in these ocular models may involve inhibition of phospholipase A2 and inducible nitric oxide synthase (iNOS) as well as the production of proinflammatory cytokine, interleukin-6. PMID- 11193753 TI - Antiflammin peptides in the regulation of inflammatory response. AB - This review focuses on the role of antiflammins in the regulation of the inflammatory response, in particular acute inflammation. The results show that antiflammins were effective on several classical models of inflammation. Preliminary data suggest that antiflammin action may be due to their ability to suppress leukocyte trafficking to the lesion. PMID- 11193754 TI - Regulation of the Clara cell secretory protein/uteroglobin promoter in lung. AB - Clara cell secretory protein/uteroglobin (CCSP/UG) is specifically expressed in the conducting airway epithelium of the lung in a differentiation-dependent manner. The proximal promoter region of the rodent CCSP/UG gene directs Clara cell specificity. Previously, it was shown that the forkhead transcription factors HNF-3 alpha and beta and the homeodomain factor TTF-1 are important transcription factors acting through this region, suggesting that they contribute to cell specificity of the CCSP/UG gene. Members of the C/EBP family of transcription factors can also interact with elements of the proximal rat and mouse CCSP/UG promoters. The onset of C/EBP alpha expression in Clara cells correlates with the strong increase of CCSP/UG expression. Thus, C/EBP alpha may play a crucial role for differentiation-dependent CCSP/UG expression. Transfection studies demonstrate that C/EBP alpha and TTF-1 can synergistically activate the murine CCSP/UG promoter. Altogether, these results suggest that C/EBP alpha, TTF-1, and HNF-3 determine the Clara cell-specific, differentiation dependent expression of the CCSP/UG gene in murine lung. The relative importance of these three transcription factors, however, differs in rabbits and humans. PMID- 11193755 TI - Uteroglobin gene transcription: what's the RUSH? AB - Prolactin enhances progesterone-dependent transcription of the rabbit uteroglobin gene. RUSH transcription factors are implicated in the signal transduction pathway. The RUSH acronym identifies key features of these nuclear phosphoproteins, that is, RING-finger motif, binds the uteroglobin promoter, structurally related to the SWI/SNF family of transcription factors, and helicase like. Cloned by recognition site screening, RUSH proteins bind to an 85-bp region (-170/-85) of the uteroglobin promoter that was subsequently identified as a novel prolactin-responsive region by promoter deletion analysis. Gel shift and linker-scanning assays further reduced the RUSH target site to -160/-110. A hexameric core of MCWTDK was identified as the RUSH-specific DNA-binding site ( 126/-121) by CASTing. This site overlaps authentic HNF3 beta and OCT-1 binding sites. A unique Type IV P-type ATPase that is embedded in the inner nuclear membrane binds the RING domain of RUSH. The conformationally flexible loop portion of this RING-finger binding protein (RFBP) extends into the nucleoplasm to contact euchromatin. The physical association of RFBP with transcriptionally active chromatin supports the speculation that RFBP targets RUSH transcription factors to the active uteroglobin promoter. PMID- 11193756 TI - Physiological regulation of uteroglobin/CCSP expression. AB - Uteroglobin/CCSP is expressed specifically in the Clara cells. This allows the gene to be used as a marker to identify the elements regulating the physiologic and cell-specific expression of this gene. The regulation of UG/CCSP by IFN-gamma was shown to be at the level of the proximal promoter by the upregulation of HNF3 beta. This has allowed the determination of the factors responsible for the expression of UG/CCSP. PMID- 11193757 TI - Tumor necrosis factor alpha stimulation of human Clara cell secretory protein production by human airway epithelial cells. AB - Clara cell secretory protein (CCSP) or uteroglobin/CC10 is a product of epithelial cells in a variety of organs including the lung. CCSP has anti inflammatory properties and may act as an inhibitor of secretory phospholipase A2's. Tumor necrosis factor alpha (TNF-alpha) is capable of inducing the expression of gene products including a variety of cytokines and chemokines in the airway epithelium that may upregulate the airway inflammatory response. Therefore, it was of interest to determine whether this proinflammatory cytokine might also induce the production of a counterregulatory protein such as CCSP, which might modulate the inflammatory response in the airway. Normal human tracheobronchial epithelial cells in primary culture and a human bronchial epithelial cell line (BEAS-2B) were studied. CCSP mRNA levels in BEAS-2B cells were detected by ribonuclease protection assay. CCSP mRNA levels increased in response to TNF-alpha (20 ng/mL) stimulation after 8-36 h, with the peak increase at 18 h. Immunoblotting of CCSP released from BEAS-2B cells into the culture media demonstrated that TNF-alpha induced the synthesis and secretion of CCSP over 8 to 18 h. Similarly, TNF stimulated the release of CCSP from human tracheobronchial epithelial cells in primary culture at 8 and 18 h. The CCSP reporter gene including 801 bases 5' of the transcription start site did not increase transcriptional activity in response to TNF-alpha stimulation. A CCSP mRNA half-life assay indicated that TNF-alpha induced increases in CCSP mRNA at least in part at a posttranscriptional level. Therefore, TNF-alpha induces airway epithelial cell expression of human CCSP and may modulate airway inflammatory responses in this manner. PMID- 11193758 TI - Pulmonary phenotype of CCSP/UG deficient mice: a consequence of CCSP deficiency or altered Clara cell function? AB - Clara cell secretory protein (CCSP) is the most abundant secreted protein within airways of the lung. Moreover, CCSP levels are modulated in human lung disease, supporting a potentially important role for CCSP and/or Clara cells in lung homeostasis. However, in vivo roles for CCSP remain elusive. A popular hypothesis is that CCSP is a regulator of the inflammatory response. The purpose of this review is to provide an overview of the phenotype of CCSP null mice and relate this phenotype to proposed functions for the protein. Phenotypic analysis of mice homozygous for the CCSP-1 null allele of the CCSP gene (CCSP-/-1) revealed susceptibility to inhaled oxidant gases. Sensitivity of CCSP-/-1 mice to inhaled ozone is unrelated to alterations in antioxidant defenses, but is associated with increased cellular injury. Additional studies investigating inflammatory control in CCSP deficient mice found no differences between wild-type and CCSP-/-1 mice in their inflammatory response to low-dose inhaled endotoxin exposure, arguing against a role for CCSP in regulation of pulmonary inflammation. The findings among CCSP-/-1 mice of ultrastructural alterations to Clara cell secretory apparatus, with associated changes in airway lining fluid protein composition, demonstrate that the CCSP-/-1 genotype results in more complex changes to airways than CCSP deficiency per se. It can be concluded that CCSP does not regulate endotoxin-induced pulmonary inflammation. Moreover, CCSP-/-1 mice represent a valuable tool for probing functional roles for Clara cells in regulation of airway lining fluid composition and lung pollutant susceptibility. PMID- 11193759 TI - Insight into the physiological function(s) of uteroglobin by gene-knockout and antisense-transgenic approaches. AB - To determine the physiological function(s) of uteroglobin (UG), a steroid inducible, homodimeric, secreted protein, we have generated transgenic mice that either are completely UG-deficient due to UG gene-knockout (UG-KO) or are partially UG-deficient due to the expression of UG antisense RNA (UG-AS). Both the UG-KO and UG-AS mice develop immunoglobulin A (IgA) nephropathy (IgAN), characterized by microhematuria, albuminuria, and renal glomerular deposition of IgA, fibronectin (Fn), collagen, and C3 complement. This phenotype of both UG-KO and UG-AS mice is virtually identical to that of human IgAN, the most common primary glomerulopathy worldwide. The molecular mechanism by which UG prevents this disease in mice appears to center around UG's interaction with Fn. Since Fn, IgA, and UG are present in circulation and high plasma levels of IgA-Fn complex have been reported in human IgAN, we sought to determine whether UG interacts with Fn and prevents Fn-Fn and/or IgA-Fn interactions, essential for abnormal tissue deposition of Fn and IgA. Our coimmunoprecipitation studies uncovered the formation of Fn-UG heteromers in vitro and these heteromers are detectable in the plasma of normal mice, but not UG-KO mice. Further, high plasma levels of IgA-Fn complex, a characteristic of human IgAN patients, were also found in UG-KO mice. Finally, coadministration of UG + Fn or UG + IgA to UG-KO mice prevented glomerular deposition of Fn and IgA, respectively. Our results define a possible molecular mechanism of IgAN and provide insight into at least one important physiological function of UG in maintaining normal renal function in mice. PMID- 11193760 TI - Uteroglobin binding proteins: regulation of cellular motility and invasion in normal and cancer cells. AB - Uteroglobin (UG) is a multifunctional, secreted protein with anti-inflammatory and antichemotactic properties. While its anti-inflammatory effects, in part, stem from the inhibition of soluble phospholipase A2 (sPLA2) activity, the mechanism(s) of its antichemotactic effects is not clearly understood. Although specific binding of UG on microsomal and plasma membranes has been reported recently, how this binding affects cellular function is not clear. Here, we report that recombinant human UG (hUG) binds to both normal and cancer cells with high affinity (20-35 nM, respectively) and specificity. Affinity cross-linking studies revealed that 125I-hUG binds to the NIH 3T3 cell surface with two proteins of apparent molecular masses of 190 and 49 kDa, respectively. UG affinity chromatography yielded similar results. While both the 190- and 49-kDa proteins were expressed in the heart, liver, and spleen, the lung and trachea expressed only the 190-kDa protein. Some cancer cells (e.g., mastocytoma, sarcoma, and lymphoma) expressed both the 190- and 49-kDa proteins. Further, using functional assays, we found that UG dramatically suppressed the motility and extracellular matrix invasion of both NIH 3T3 and some cancer cells. In order to further characterize the anti-ECM-invasive properties of UG, we induced expression of hUG into cancer cell lines derived from organs that, under physiological circumstances, secrete UG at a high level. Interestingly, it has been reported that a high percentage of the adenocarcinomas arising from the same organs fail to express UG. Our results on induced hUG expression in these cells show that inhibition of motility and ECM invasion requires the expression of both UG and its binding proteins. Taken together, our data define receptor-mediated functions of UG in which this protein regulates vital cellular functions by both autocrine and paracrine pathways. PMID- 11193761 TI - The role of CC10 in pulmonary carcinogenesis: from a marker to tumor suppression. AB - CC10 is infrequently expressed in human non-small cell lung cancers (NSCLCs), despite being abundantly produced by progenitor cells for normal and neoplastic epithelium. Many abnormalities in the surrounding lung associated with field carcinogenesis, which reflect prolonged exposure to such carcinogens as tobacco smoke, also revealed altered expression of CC10. Exposure of hamsters and mice to the tobacco-specific carcinogen NNK led to reduced CC10 expression, which was partially reversible. Overexpression of CC10 in immortalized bronchial epithelial cells delayed the induction of anchorage-independent growth in response to NNK. The data suggest that downregulation of CC10 contributes to carcinogenesis because CC10 antagonizes the neoplastic phenotype. PMID- 11193762 TI - All human genes of the uteroglobin family are localized on chromosome 11q12.2 and form a dense cluster. AB - Rabbit uteroglobin is the founder member of a family of mammalian proteins that has expanded to more than 20 members within the last few years. All members are small, secretory, rarely glycosylated dimeric proteins with unclear physiological functions and are mainly expressed in mucosal tissues. A phylogenetic analysis shows that the family can be grouped into five subfamilies, A to E. Subfamily A contains rabbit uteroglobin and its orthologues from various species; most of these have been described to form antiparallel homodimers via two intermolecular disulfide bonds. All other subfamily members contain a third conserved cysteine and, from existing biochemical data, it can be predicted that a member of subfamily B or C will likely form heterodimers with a partner from subfamily E or D, respectively. Besides the mentioned cysteines, only one central lysine is conserved in all family members. In the known uteroglobin structures, this lysine forms an exposed salt bridge with an aspartate side chain, which is conserved in almost all sequences. Using radiation hybrid mapping and P1 clone analysis and utilizing data from the human genome project, we show that all known five human family members (Clara cell 10-kDa protein, lipophilins A and B, lacryglobin, mammaglobin) and a new member, we call lymphoglobin, are localized on chromosome 11q12.2 in a dense cluster spanning not more than approximately 400 kbp. PMID- 11193763 TI - Development of an enzyme-linked immunosorbent assay for Clara cell 10-kDa protein: in pursuit of clinical significance of sera in patients with asthma and sarcoidosis. AB - We have produced nine monoclonal antibodies to human CC10/protein-1 and analyzed their characterization. TY-5, TY-7, and TY-8 recognized restricted possible hydrophobic epitopes and their binding to CC10 prevented the other clones from CC10 binding, suggesting that these antibodies induce strong conformational change. TY-1, TY-2, TY-3, TY-6, and 6D4 recognize amino acid residues 61-68 and the presence of disulfide bonds might be essential for epitope expression of these five clones. The best combination was TY-1 and TY-2 in developing an enzyme linked immunosorbent assay (ELISA), whereas TY-5 was most suitable for immunohistochemistry and immunoblotting. We found significantly lower serum CC10 levels in asthmatic subjects and higher serum CC10 levels in sarcoidosis subjects than in controls. Data of CC10 levels in BAL fluids of sarcoidosis subjects were similar to those in the circulation. CC10-positive epithelial cells were significantly lower in small airways of asthmatic subjects than in controls, and CC10-positive epithelial cells were inversely correlated with T cell and mast cell accumulation in the airways of asthmatic subjects. CC10 may be a downregulator in both Th1- and Th2-mediated chronic inflammatory diseases. The use of these MoAbs and recombinant CC10 is a powerful tool to investigate the clinical roles of CC10/P1 and the structure and function of CC10/P1. PMID- 11193764 TI - Rationale for the development of recombinant human CC10 as a therapeutic for inflammatory and fibrotic disease. AB - CC10/uteroglobin is a remarkable protein whose physiological roles have only recently been explored in vivo. Both transgenic mice that have been rendered deficient and humans that have been characterized as deficient in this protein exhibit tendencies toward inflammatory, fibrotic, and oncologic disease, demonstrating the potential of the protein as a therapeutic agent. The protein itself is an excellent candidate for clinical development because of its inherent physical properties. It is relatively small, resistant to proteases, stable to extremes of heat and pH, and can be produced by recombinant methods. The physiological roles of this multifunctional protein continue to be uncovered as research progresses in vitro, in animals, and eventually in humans. The pathways through which CC10 mediates its effects, its receptors, and other family members will be a rich source of exciting research, as well as potential diagnostic and therapeutic agents. This paper is an introductory, noncomprehensive review of some of the scientific and medical rationale in support of CC10-based therapies in selected clinical applications. PMID- 11193765 TI - C/EBP alpha and TTF-1 synergistically transactivate the Clara cell secretory protein gene. PMID- 11193766 TI - Human uteroglobin gene polymorphisms and genetic susceptibility to asthma. PMID- 11193767 TI - Amino acid residues in alpha-helix-3 of human uteroglobin are critical for its phospholipase A2 inhibitory activity. PMID- 11193768 TI - Mammaglobin complexes with BU101 in breast tissue. PMID- 11193769 TI - Uteroglobin in situ hybridization: novel monitoring of epithelial differentiation in the rabbit endometrium. PMID- 11193770 TI - Prolactin augments progesterone-dependent expression of a nuclear P-type ATPase that associates with the RING domain of RUSH transcription factors in the endometrium. PMID- 11193771 TI - A novel in situ method of SV40 transfection for the establishment of immortal pulmonary alveolar type II cell lines. PMID- 11193772 TI - Uteroglobin expression and release in the human endometrium. PMID- 11193773 TI - Expression of inflammatory cytokines in a mouse transformed Clara cell line by tumor necrosis factor-alpha. PMID- 11193774 TI - Binding of rhCC10 to fibronectin and its effect on cellular adhesion. PMID- 11193775 TI - Mammaglobin as a marker for the detection of tumor cells in the peripheral blood of breast cancer patients. PMID- 11193776 TI - In vivo and in vitro analysis of hyperoxia-induced gene expression in mouse lung and mouse transformed Clara cells. PMID- 11193777 TI - Uteroglobin/Clara cell 10-kDa family of proteins: nomenclature committee report. PMID- 11193778 TI - Clara cell proteins. AB - Clara cells are nonciliated, nonmucous, secretory cells of the pulmonary airways. These cells are known to secrete a variety of proteins, including Clara cell 10 kDa protein/uteroglobin. This protein consists of a homodimer of 70-77 amino acid polypeptides arranged in antiparallel fashion. In vitro testing suggests that the protein suppresses inflammation. The physiologic role of the protein remains to be determined. PMID- 11193779 TI - Secretory lipophilins: a tale of two species. AB - Secretory lipophilins are "lipid-loving" proteins that are major constituents of several mammalian secretions, including the prostatic fluid of rats and the tears of humans and rabbits. These proteins form covalent heterodimers that are stabilized by three intramolecular cystine disulfide bonds. The heterodimers, some of which are glycosylated, may undergo additional non-covalent assembly to form tetramers. The peptide components found in secretory lipophilins are from two subfamilies: lipophilins A/B and lipophilin C. The C subfamily members described in this report are three rabbit and one human lipophilin, plus human mammaglobin and the C3 subunit of rat prostatein. Human A/B and C lipophilins are expressed by many tissues and are especially prominent in endocrine-responsive organs. The gene for human lipophilin B resides at chromosome 10q22-23. This region harbors the PTEN/MMAC1 gene and is believed to contain additional tumor suppressor genes. Although the functions of secretory lipophilins are imperfectly understood, their abundance in glandular secretions and in hormone-responsive tissues suggests that they deserve considerably more attention than they have received to date. PMID- 11193780 TI - Clara cell secretory protein (CC16): features as a peripheral lung biomarker. AB - Clara cell protein (CC16 or CC10) is a 15.8-kDa protein secreted all along the tracheobronchial tree and especially in the terminal bronchioles where Clara cells are localized. Even though the exact in vivo function of CC16 remains to be clarified, evidence is accumulating that CC16 plays an important protective role in the respiratory tract against oxidative stress and inflammatory response. CC16, however, presents also a major interest as a peripheral lung marker for assessing the cellular integrity or the permeability of the lung epithelium. The serum concentrations of CC16 are decreased in subjects with chronic lung damage caused by tobacco smoke and other air pollutants as a consequence of the destruction of Clara cells. By contrast, serum CC16 increases in acute or chronic lung disorders characterized by an increased airways permeability. The sensitivity of serum CC16 to an increased leakiness of the lung allows for the detection of defects of the epithelial barrier at ozone levels below current air quality guidelines. Although the clinical significance of these early epithelial changes detected by serum CC16 remains to be determined, these results clearly show that the assay in serum of lung secretory proteins such as CC16 represents a new noninvasive approach to evaluate the integrity of the respiratory tract. PMID- 11193781 TI - Mammaglobin, a breast-specific gene, and its utility as a marker for breast cancer. AB - The mammaglobin gene encodes a 10-kDa glycoprotein that is distantly related to a family of proteins that includes rat estramustine binding protein (EMBP)/prostatein and human Clara cell 10-kDa protein (CC10)/uteroglobin. Among normal adult tissues, mammaglobin mRNA expression has been detected only in the mammary gland. As an initial step to determine mammaglobin's clinical utility as a breast tumor marker, we evaluated the frequency and specificity with which mammaglobin expression could be detected in primary breast tumors, metastatic breast tumors, and breast tumor cells present in the peripheral circulation. Approximately 80% of all primary and metastatic breast tumors examined were strongly immunopositive for mammaglobin protein, and staining was independent of tumor grade. Among peripheral stem cell collections from breast cancer patients, mammaglobin mRNA could be detected in 60% of cases. Recent work has identified the secreted mammaglobin protein in the sera of some breast cancer patients using both Western blot and ELISA. This study demonstrates that the detection of mammaglobin protein and mRNA in clinical samples may be a useful marker for primary, metastatic, and occult breast cancer. PMID- 11193782 TI - The discovery of uteroglobin and its significance for reproductive biology and endocrinology. AB - The discovery of uteroglobin resulted from investigations on the biochemical composition of oviductal and uterine secretions of the rabbit and other mammals. These determinations about physiological composition were urgently requested to prepare culture media for research on early mammalian development in vitro. Discovery of significant proteins during the sixties reflected the laboratory skills of that time. Protein characterization was achieved by isolation via Sephadex gels, electrophoresis on polyacrylamide gels, and finally immunoprecipitation using classical polyclonal antibodies. The molecular biology was not yet established. Uteroglobin could be found as the major protein component of rabbit uterine secretion. From the beginning, it was already identified as an unusually small, spheric uterine secretory molecule without any carbohydrates--hence its name. Uteroglobin was the first mammalian protein that turned out to be progesterone-regulated and, at the same time, released in mg amounts actually in one organ compartment. Moreover, uteroglobin and its gene proved to be a reliable model for the description of progesterone/progesterone receptor complex action at the DNA level. After its original observation in the uterus, however, uteroglobin was detected also in several other organs, for example, the epididymis, the seminal vesicle, and the lung. Initially, it could not be found in the blood, which challenged the hypothesis that uteroglobin specifically should operate by local activation rather than by a humoral or endocrine effect. Later, though, the human uteroglobin molecule, isolated from blood filtrate, was used for detailed structural analyses. The rabbit uteroglobin model certainly was beneficial for reproductive biological research. Experimental interference with steroid hormone regulation during preimplantation presented surprising effects, which led to the discovery of the transposition of the implantation window. The uterine secretion protein patterns, in particular the uteroglobin fraction and the beta-glycoprotein fraction, served as decisive marker profiles to identify the biological stage of the intrauterine microenvironment during preimplantation. This diagnostic procedure, using only protein parameters, enabled us to precisely predict the receptive stage of the endometrium for donated blastocysts to achieve implantation successfully. PMID- 11193783 TI - The uteroglobin fold. AB - Uteroglobin (UTG) forms a fascinating homodimeric structure that binds small- to medium-sized ligands through an internal hydrophobic cavity, located at the interface between the two monomers. Previous studies have shown that UTG fold is not limited to the UTG/CC10 family, whose sequence/structure relationships are highlighted here, but can be extended to the cap domain of Xanthobacter autotrophicus haloalkane dehalogenase. We show here that UTG fold is adopted by several other cap domains within the alpha/beta hydrolase family, making it a well-suited "geode" structure allowing it to sequester various hydrophobic molecules. Additionally, some data about a new crystal form of oxidized rabbit UTG are presented, completing previous structural studies, as well as results from molecular dynamics, suggesting an alternative way for the ligand to reach the internal cavity. PMID- 11193784 TI - Alzheimer's disease: a compendium of current theories. Proceedings of a conference. April 30-May 2, 1999. Orlando, Florida, USA. PMID- 11193785 TI - Genetic factors in the genesis of Alzheimer's disease. AB - At least four different genes have been identified that are associated with inherited susceptibiltiy to Alzheimer's disease. Some of the genes are highly penetrant (PS1, PS2, beta APP); the other, APOE, is a weaker susceptibility factor. Several additional genes are suspected to exist but have not yet been cloned. PMID- 11193786 TI - Comprehensive theory of Alzheimer's disease. The effects of cholesterol on membrane receptor trafficking. AB - Neurotrophic factors (NTFs), once known for their role in development, have recently been shown to contribute to the maintenance and plasticity of the adult nervous system. This knowledge has provoked hypotheses implicating NTFs in neurodegenerative conditions, particularly Alzheimer's disease (AD). Many of these hypotheses, however, fail to place the possibility of trophic factor dysfunction in the context of recent advances in the molecular pathogenesis of AD. Most notable has been the discovery of several genetic risk factors and three causative Alzheimer's genes. Genetic advances, in turn, have not yet shed much light on an important pathological feature of AD, synaptic loss. We propose here an hypothesis based on recent cell biological research that attempts to integrate findings in these areas. Our hypothesis states that AD pathogenesis results from disruption of cholesterol uptake and metabolism and that this in turn results in abnormal trafficking of membrane proteins critical to normal neuronal function and synaptic plasticity. PMID- 11193787 TI - The brain's microenvironment, early functional loss, and the conversion to Alzheimer's disease. AB - We hypothesize that insults in the local microenvironment may cause selective, local neurite degeneration by apoptotic-like mechanisms, leading to the loss of synaptic connectivity observed in the Alzheimer disease brain. This may be an early mechanism of neurodegeneration, potentially contributing to neuronal vulnerability and disease pathogenesis. PMID- 11193788 TI - A "protease activation cascade" in the pathogenesis of Alzheimer's disease. AB - A pathway to Alzheimer's disease (AD) relevant to sporadic AD pathogenesis is described that involves the early and progressive activation of proteolytic systems including, but not limited to, the calpain-calpastatin and endosomal lysosomal systems. Activation of these proteolytic systems is initiated by normal brain aging and is propelled by the genetic and environmental factors known to increase AD risk. Recent studies show how cathepsins and calpains, acting directly or indirectly through other proteolytic pathways and cellular signaling cascades, may promote beta-amyloidogenesis, neurofibrillary pathology, as well as mediate neurodegeneration in AD. PMID- 11193789 TI - A perspective on inflammation in Alzheimer's disease. AB - Although there have been hundreds of recent papers that document a role for innate inflammatory responses in Alzheimer's disease (AD), several global issues and organizational points are still worth emphasizing. These include etiologic versus pathogenic roles for AD inflammation, the potency of AD inflammation, the sources of AD inflammation, and the highly interactive nature of AD inflammatory responses. PMID- 11193790 TI - Impaired cerebromicrovascular perfusion. Summary of evidence in support of its causality in Alzheimer's disease. AB - After nearly a century of inquiry, the cause of Alzheimer's disease (AD) remains to be found. In this review, basic and clinical evidence is presented that assembles and hypothetically explains most of the key pathologic events associated with the development of AD. These pathologic events are triggered in AD by impaired cerebral perfusion originating in the microvasculature that affects the optimal delivery of glucose and oxygen and results in an energy metabolic breakdown of brain cell biosynthetic and synaptic pathways. We propose that two factors must be present before cognitive dysfunction and neurodegeneration is expressed in the AD brain: (1) advanced aging, (2) presence of a condition that lowers cerebral perfusion, such as a vascular risk factor. The first factor introduces a normal but potentially menacing process that lowers cerebral blood flow in proportion to increased aging, while the second factor adds a crucial burden that further lowers brain perfusion and places vulnerable neurons in a state of metabolic compromise leading to a death pathway. These two factors will lead to a critically attained threshold of cerebral hypoperfusion (CATCH). CATCH is a self-sustaining and progressive circulatory insufficiency that will destabilize neurons, synapses, neurotransmission, and cognitive function, creating in its wake a neurodegenerative process characterized by the formation of senile plaques, neurofibrillary tangles, amyloid angiopathy, and, in some cases, Lewy bodies. Since any of a considerable number of vessel-related conditions must be present in the aging individual for cognition to be affected, CATCH supports the heterogeneic disease profile assumed to be characteristic of the AD syndrome. A brief discussion of target therapy based on the proposed pathogenesis of AD is also reviewed. PMID- 11193791 TI - Existing data suggest that Alzheimer's disease is preventable. AB - The ultimate goal of Alzheimer's disease (AD) research is to prevent the onset of the neurodegenerative process and thereby allow successful aging without cognitive decline. Herein I argue that a simple and effective preventative approach for AD may be in hand. AD is a disorder associated with the aging process and is, accordingly, characterized by cellular and molecular changes that occur in age-related diseases in other organ systems. Such changes include increased levels of oxidative stress, perturbed energy metabolism, and accumulation of insoluble (oxidatively modified) proteins (prominent among which are amyloid beta-peptide and tau). The risk of several other prominent age related disorders, including cardiovascular disease, cancer, and diabetes, is known to be influenced by the level of food intake--high food intake increases risk, and low food intake reduces risk. An overwhelming body of data from studies of rodents and monkeys has documented the profound beneficial effects of dietary restriction (DR) in extending life span and reducing the incidence of age-related diseases. Reduced levels of cellular oxidative stress and enhancement of energy homeostasis contribute to the beneficial effects of DR. Recent findings suggest that DR may enhance resistance of neurons in the brain to metabolic, excitotoxic, and oxidative insults relevant to the pathogenesis of AD and other neurodegenerative disorders. While further studies will be required to establish the extent to which DR will reduce the incidence of AD, it would seem prudent (based on existing data) to recommend DR as widely applicable preventative approach for age-related disorders including neurodegenerative disorders. PMID- 11193792 TI - Oxidative stress leading to loss of critical proteases in Alzheimer's disease. An alternative view of the etiology of AD. AB - An alternative view of the etiology of Alzheimer's disease is suggested which focuses on the relationship between oxidative stress and the decrease in proteases seen in aging. Proteases act to govern the acceleration of the pathology of aging and, as damage from oxidative stress increases, the loss of proteases in at-risk persons leads to symptoms of AD. Controlling the damage to proteases or controlling the generator(s) of oxidative stress may help to control the onset or progression of Alzheimer's disease. PMID- 11193793 TI - Oxidative metabolism. AB - There is a large body of evidence showing both metabolic defects and oxidative damage in Alzheimer's disease. Studies of cybrid cell lines show reduced cytochrome oxidase. There is also substantial evidence for a defect in alpha ketoglutarate dehydrogenase. It is therefore possible that therapeutic strategies to improve brain metabolism or ameliorate oxidative damage might be useful in treating Alzheimer's disease. PMID- 11193794 TI - Toward a comprehensive theory for Alzheimer's disease. Hypothesis: Alzheimer's disease is caused by the cerebral accumulation and cytotoxicity of amyloid beta protein. AB - A central challenge of research on Alzheimer's disease (AD) is to assemble the enormous body of scientific observations about the disorder, some of them seemingly in conflict with others, into a coherent and credible mechanism of pathogenesis. In this article, I attempt to synthesize the disparate findings on AD into a unified sequence that essentially begins with alterations in the production or clearance of the amyloid beta-protein (A beta). Mounting evidence from many laboratories supports an A beta accumulation in limbic and association cortices as the fundamental initiator of the disease, with attendant therapeutic implications. PMID- 11193795 TI - The mitochondrial spiral. An adequate cause of dementia in the Alzheimer's syndrome. AB - A variety of chronic, relatively low-grade injuries to the brain occur in Alzheimer's disease (AD). The extent to which each of these contributes to the clinical syndrome is unclear. Several of the abnormalities that occur in AD brain can cause dementia by themselves, even in people who do not have the neuropathological hallmarks of AD. Prominent among these abnormalities is a deleterious "mitochondrial spiral," which consists of reduced brain metabolism, oxidative stress, and calcium dysregulation. The hypothesis presented in this paper is that the mitochondrial spiral contributes to dementia in AD and presents a reasonable target for the development of new approaches to the treatment of this syndrome. PMID- 11193796 TI - Toward a comprehensive theory of Alzheimer's disease--challenges, caveats, and parameters. AB - The task of developing a unifying theory of Alzheimer's disease faces several impediments. The most difficult include: the impact of scientific orthodoxy on the acceptance of new ideas; the uncertain relationship between aging and disease(s); the long time course of the degenerative process; the heterogeneity in the genotype and phenotype of the disease; the complex interactions among genetic and other risk factors (many of which are not yet known); the poorly understood nonlinear relationships between the neurobiological and the clinical phenotypes of the disease--namely, viewing clinical symptoms as emergent behavior(s) of a complex system; and the paucity of appropriate models or modeling systems for human disease(s) such as Alzheimer's. PMID- 11193797 TI - The pathogenesis of Alzheimer's disease. Is amyloid beta-protein the beginning or the end? AB - A central issue in Alzheimer's disease research is whether amyloid beta-protein (A beta) is a cause or effect of the pathogenic process. Several independent lines of evidence argue for causality, although human clinical trials may be required to finally settle the issue. PMID- 11193798 TI - Pathways to primary neurodegenerative disease. AB - Genetic analysis has revealed the pathogenic lesions that cause autosomal dominant Alzheimer's disease, prion disease, and some forms of Parkinson's disease. Molecular biological experiments based on these genetic findings allow a hypothesis to be configured linking these and the other diseases in which tangles or Lewy bodies are a pathological feature. In this article, this hypothesis is presented in the context of deriving curative treatments for these disorders. PMID- 11193799 TI - Arson. Tracking the culprit in Alzheimer's disease. AB - By focusing on the lesions in Alzheimer's disease, and regarding them as either critical or irrelevant, researchers may have missed much regarding the origin and pathogenesis of this disease. In this article we consider that the lesions are so obvious not only because they are pathognomonic for Alzheimer's disease, but also because they represent a major departure from normal physiology. We suggest that these myriad pathological changes are homeostatic compensatory mechanisms to aging. PMID- 11193800 TI - Synaptic structure and function in transgenic APP mice. AB - Efforts using transgenic mice are being made to understand the molecular and structural basis for dementia in Alzheimer's disease. Transgenic mice 12 to 18 months of age with amyloid plaques and impaired cognition show no neuronal or synaptic loss in the CA1 hippocampal subfield. Electrophysiological studies may yield new insights. PMID- 11193801 TI - A plasticity-based theory of the pathogenesis of Alzheimer's disease. AB - Amyloid plaques (APs) and neurofibrillary tangles (NFTs) are the two diagnostic markers of Alzheimer's disease (AD). The neuropsychological features of AD are closely correlated with the distribution of the NFTs and therefore favor a disease process revolving around neurofibrillary degeneration. The genetics, however, favor a disease process revolving around the APs, principally because mutations in the amyloid precursor protein (A beta PP) are sufficient to cause AD. The inability to reconcile these two aspects of AD has prevented the formulation of a unified theory of pathogenesis. It is interesting to note that all genetic causes and risk factors of AD can increase the physiological burden of neuroplasticity. My hypothesis is that the resultant intensification of the plasticity burden leads to an initially adaptive upregulation of tau phosphorylation and A beta PP turnover, to the subsequent formation of NFTs and APs as independent consequences of excessive plasticity-related cellular activity, and to the eventual loss of neurons, dendrites, and synapses as the ultimate expression of plasticity failure. The two pathological markers of AD are therefore independent manifestations of a more fundamental process through which the many different genotypes of AD trigger an identical clinical and neuropathological phenotype. PMID- 11193802 TI - Vulnerability of select neuronal types to Alzheimer's disease. AB - From a morphological perspective, Alzheimer's disease (AD) is primarily a degenerative disorder of the neuronal cytoskeleton involving lipofuscin-laden cortical projection neurons with long, thin, and sparsely myelinated axons. The neocortical primary fields, relatively small in extent but functionally sophisticated, exhibit an early and brief myelination cycle, whereas the much more expansive but relatively simply organized association areas undergo a late and prolonged myelination process. The greater the degree of myelination and the less intense the pigmentation, the more resistant a given projection neuron may be to oxidative stress as well as to the development of AD-related neurofibrillary changes and vice versa. The neurofibrillary pathology commences from those cortical areas that are less completely myelinated and gradually progresses to the most functionally developed cortical fields that display the highest degree of myelination, thereby reflecting a hierarchy in the susceptibility of diverse cortical areas to the evolution of the AD-associated cytoskeletal pathology. PMID- 11193803 TI - "Fatal attractions" of proteins. A comprehensive hypothetical mechanism underlying Alzheimer's disease and other neurodegenerative disorders. AB - Abnormal protein-protein interactions that result in the formation of intracellular and extracellular aggregates of proteinacious fibrils are common neuropathological features of many, albeit diverse, neurodegenerative disorders, such as sporadic and familial Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and prion encephalopathies. Indeed, increasing evidence suggests that abnormal protein-protein interactions and/or the lesions that result from the aggregation of pathological protein fibrils could play a mechanistic role in the dysfunction and death of neurons or glial cells in neurodegenerative diseases. Here we propose that "fatal attractions" between brain proteins are the key pathological events underlying Alzheimer's disease and a large number of other seemingly diverse neurodegenerative disorders. This hypothesis predicts that the abnormal interaction between normal brain proteins alters their conformation and promotes the assembly of these pathological conformers into filaments that progressively accumulate as intracellular or extracellular fibrous deposits in the central nervous system. Further, the transformation of the normal proteins into pathological conformers is predicted to result in losses of critical functions, and the disease proteins or their progressive accumulation into filamentous aggregates are predicted to acquire neurotoxic properties, all of which culminate in the dysfunction and death of affected brain cells. Thus, the "fatal attractions" hypothesis describes a plausible unifying mechanism that accounts for the onset/progression of Alzheimer's disease and a large number of other seemingly unrelated neurodegenerative disorders characterized neuropathologically by filamentous brain lesions formed by different proteins. PMID- 11193804 TI - The role of synaptic proteins in Alzheimer's disease. AB - Synaptic damage is an early event common to neurodegenerative disorders such as Alzheimer's disease (AD) and is the best correlate to the cognitive impairment found in these patients. Recent studies have shown that several of the molecules involved in neurodegenerative disorders are in fact synaptic proteins with amyloidogenic potential (SPWAP). Here we propose a unified theory to explain the neurodegenerative process in AD based on the idea that abnormal folding and/or aggregation of these molecules leads to cell death. The most important predictions of this hypothesis are that: (1) there are other yet unknown SPWAP that might be involved in AD, and their identity can be predicted by defining what makes a protein amyloidogenic; (2) there are endogenous anti-amyloidogenic molecules that regulate the aggregation state of SPWAP; and (3) there might be forms of the disease associated with decreased production of endogenous anti amyloidogenic molecules or with unbalance of pro- versus anti-amyloidogenic factors. PMID- 11193805 TI - The long reach of evolution and development. Effects on the Alzheimer brain. AB - Genes that cause late-onset neurodegenerative disease may have the property of evolvability. Their tendency to collect mutations may have contributed to the rapid evolution of the brain. PMID- 11193806 TI - A very incomplete comprehensive theory of Alzheimer's disease. AB - For this meeting, I was asked to put down some ideas toward the development of theories of the etiology and pathogenesis of Alzheimer's disease. This charge has led to a first attempt to consider the "big picture," at least as seen from my viewpoint. Many details of the schemes I propose could be discussed in much greater depth, but I have tried to avoid getting bogged down in this way. It is sometimes valuable to step back from our own little domains of research and to attempt to integrate what we have collectively discovered into a more comprehensive framework. PMID- 11193807 TI - Apolipoprotein E and Alzheimer's disease. A role in amyloid catabolism. AB - It has been shown over the past few years that apolipoprotein E (apoE) plays a central role in the brain response to injury and neurodegeneration in mammalian species. The coordinated expression of apoE and its different receptors, the so called LDL receptor family, appears to regulate the transport of cholesterol and phospholipids during the early and middle phases of the reinnervation in the adult mammalian brain. As neurons undergo dendritic remodelling and synaptogenesis using cholesterol internalization through the apoE/LDL receptor pathway, they progressively shut down 3,3-hydroxymethylglutaryl-Coenzyme A (HMG CoA) reductase activity, the rate-limiting enzyme in the synthesis of cholesterol. These results suggest that cholesterol delivery and synthesis in the brain are tightly regulated through an apoE-dependent mechanism. The discovery that the apolipoprotein e4 allele is strongly linked to both sporadic and familial late-onset Alzheimer's disease (AD) has raised the possibility that a dysfunction of lipid transport could explain the poor compensatory synaptogenesis reported by several independent research groups in the brain of AD subjects. Recently, it has been shown that alterations of cholesterol homeostasis in the brain by exogenous administration of dietary cholesterol, or through inhibition of cholesterol synthesis, markedly affect beta amyloid production (1-40 and 1-42) and deposition and significantly impair amyloid precursor protein (APP) metabolism. In vivo, it has been shown that breeding of APP-overexpressing mice with apoE knockout mice completely abolishes amyloid plaque deposition in the brain of hybrid animals, without affecting beta amyloid steady state levels. Conversely, introduction of the human apoE3 and apoE4 genes in APP-overexpressing mice drastically reduced beta amyloid deposition in the brain of hybrid mice, confirming the proposed biological role of apoE in the clearance of extracellular beta amyloid. These results indicate that lipid homeostasis is controlled in large part by the apoE lipoprotein transport system in the extracellular space, whereas alterations in intracellular lipid homeostasis markedly affect APP processing, beta amyloid production and plaque formation in vivo. The convergence of the so-called amyloid cascade hypothesis (Hardy et al., 1992) and of the apoE/lipid recycling cascade model (Poirier, 1994) is consistent with the notion that alterations in lipid homeostasis could serve as the common denominator for apoE and beta amyloid dysfunctions in Alzheimer's disease. It is also interesting to note that lipid homeostasis is also a central feature of one of the most important neurotransmitter systems in the brain: the cholinergic system. This system is unique in the CNS since it relies heavily on lipid bioavailability to locally synthesize acetylcholine. It is thus quite tempting to propose that two of the most common neuropathologic landmarks of AD--namely, cholinergic dysfunction and amyloid deposition--may in fact depend on the integrity of local lipid homeostatic processes, which in turn are strongly dependent upon proper lipid delivery by the apoE transport system. PMID- 11193808 TI - Apolipoprotein E and Alzheimer's disease. AB - The specific molecular pathway by which apolipoprotein E modifies the expression of Alzheimer's disease remains elusive. Isoform-specific interactions of apolipoprotein E with other molecules determine the outcome from other neurologic disorders and may provide more tractable model systems. PMID- 11193809 TI - Estrogens and estrogen-like non-feminizing compounds. Their role in the prevention and treatment of Alzheimer's disease. AB - The present position paper is intended to provide evidence that estrogen deprivation contributes to the occurrence and course of Alzheimer's disease (AD) and that currently available estrogen preparations may be useful in the prevention and treatment of AD in women. Additionally, there is now substantial preclinical evidence to support the development of novel non-feminizing estrogens for use in male and female subjects for the protection of neurons from damage and death that underlies the neuropathology of AD. Estrogens and non-feminizing estrogen-like compounds may exert their beneficial effects in AD through a variety of mechanisms, directly through their neuroprotective actions and indirectly through their neurotrophic effects. Inasmuch as estrogens are comparatively free of both acute and chronic toxicities, and non-feminizing estrogens are expected to be even safer, their use for years to decades for the prevention or treatment of AD is possible. PMID- 11193810 TI - Alzheimer's disease and some speculations about the evolution of its modifiers. AB - In this paper we consider the evolution of Alzheimer's-like neuropathology in the aging primate brain. In particular, we examine the evolutionary pressures that have likely selected for the neuroprotective effects of estrogen and of the apolipoprotein E2 and E3 isoforms. We analyze this in the context of the altricial nature of new-born primates, their long period of dependency on competent maternal care, and the requirement of cognitive intactness for such competency. PMID- 11193811 TI - In vitro evaluation of VIP/PACAP receptors in healthy and diseased human tissues. Clinical implications. AB - The evaluation of peptide receptors in man is relevant to identifying the physiological target tissues of a given peptide and to selecting diseases with a sufficient receptor overexpression for diagnostic or therapeutic intervention. VIP/PACAP receptors have been evaluated in normal and diseased human non-neuronal tissues by using in vitro receptor autoradiography with 125I-VIP or 125I-PACAP in tissue sections. As assessed by subtype-selective VIP analogs, VIP receptors of the VPAC1 subtype are found in a wide variety of tissues including liver, breast, kidney, prostate, ureter, bladder, pancreatic ducts, gastrointestinal mucosa, lung, thyroid, adipose, and lymphoid tissues. VPAC2 receptors are predominantly found in vessels and smooth muscles, whereas PAC1 receptors are present in the adrenal medulla. VIP/PACAP receptors are expressed in the majority of the most frequently occurring human tumors, including breast, prostate, pancreas, lung, colon, stomach, liver, and bladder carcinomas, as well as lymphomas and meningiomas, predominantly as VPAC1 receptors, as do their tissues of origin. Although leiomyomas predominantly express VPAC2 receptors, glial tumors, pituitary adenomas, neuroblastomas, paragangliomas, pheochromocytomas, and endometrial carcinomas preferentially express PAC1 receptors. The very wide distribution of VIP/PACAP receptors in the normal human body is indicative of the key role of these peptides in human physiology and pathophysiology. Moreover, the receptor expression in tumors is the molecular basis for clinical applications of VIP/PACAP such as in vivo scintigraphy and radiotherapy of tumors as well as VIP/PACAP analog treatment for tumor growth inhibition. PMID- 11193812 TI - Neuropeptide action in sympathetic ganglia. Evidence for distinct functions in intact and axotomized ganglia. PMID- 11193813 TI - Chemokines released from astroglia by vasoactive intestinal peptide. Mechanism of neuroprotection from HIV envelope protein toxicity. AB - The mechanism through which VIP prevents neurotoxicity associated with HIV envelope protein has been shown to involve the release of a beta-chemokine, MIP-1 alpha. Astrocytes stimulated with subnanomolar concentrations of VIP caused the release of MIP-1 alpha and RANTES, both of which have been shown to prevent neuronal cell death associated with gp120. It is further proposed that gp120 causes neuronal cell death, in part, by competing with endogenous chemokines at various chemokines receptors in the brain that are necessary for neuronal survival. Although the chemokines are known to be mediators of inflammation, our studies suggest that these compounds have additional roles as neuroprotective agents that depend on the concentration of chemokine, cellular microenvironment, and stage of development of target neurons. Our studies further imply that in a developing system, stimulation with a MIP-1 alpha like substance is necessary for neuronal survival and interference with this action results in neuronal cell death. PMID- 11193814 TI - A novel VIP responsive gene. Activity dependent neuroprotective protein. AB - Activity dependent neuroprotective protein (ADNP, 828 amino acids, pI 5.99) is a glial-derived protein that contains a femtomolar active neuroprotective peptide, NAPVSIPQ (NAP). VIP induces a two- to threefold increase in ADNP mRNA in astrocytes, suggesting that ADNP is a VIP-responsive gene. ADNP is widely distributed in the mouse hippocampus, cerebellum, and cerebral cortex. VIP has been shown to possess neuroprotective activity that may be exerted through the activation of glial proteins. We suggest that ADNP may be part of the VIP protection pathway through the femtomolar-acting NAP and through putative interaction with other macromolecules. PMID- 11193815 TI - Neuroprotective effects of PACAP38 in a rat model of transient focal ischemia under various experimental conditions. AB - In the study reported here, we investigated the neuroprotective effect of PACAP38 in a rat model of middle cerebral artery occlusion (MCAO) under various experimental conditions. Stroke patients often develop mild hyperthermia that increases the infarct size and worsens the outcome. We compared the neuroprotective effect of PACAP38 in normothermic and moderately hyperthermic animals. Brain damage was more extensive in the hyperthermic animals, but PACAP38 significantly reduced the infarct size, measured 48 h after MCAO, in both the normothermic and the moderately hyperthermic animals, by more than 50%. However, a significant neuroprotection with PACAP38 could only be demonstrated when animals with no definite circling behavior and/or convulsions were excluded from the evaluations. In conclusion, moderate hyperthermia did not influence the effect of PACAP38, but animals with questionable brain damage or convulsions must be excluded from the sample in order to demonstrate the neuroprotection with PACAP38. PMID- 11193816 TI - PACAP action in nervous system development, regeneration, and neuroblastoma cell proliferation. AB - Pituitary adenylate cyclase activating peptide (PACAP) may play a role in neurogenesis, nerve injury, and neural tumor growth. A PACAP ligand receptor system functionally coupled to cAMP production was found to be expressed in the embryonic mouse neural tube at the onset of neurogenesis. PACAP was found to inhibit DNA synthesis and antagonize sonic hedgehog signaling in cells isolated from the neural tube, suggesting that PACAP interacts with patterning factors to regulate neurogenesis and phenotypic specification in the developing CNS. PACAP and PACAP receptor (PAC1) mRNA levels were strongly increased and decreased, respectively, in motor neurons in adult rats after facial nerve axotomy, indicating that PACAP may also act in nerve regeneration. Experiments using a neuroblastoma tumor cell line model indicate that PACAP may execute growth related functions by activating MAP kinase in addition to cAMP-dependent protein kinase A. PMID- 11193817 TI - Characterization of intestinal receptors for VIP and PACAP in rat and in PAC1 receptor knockout mouse. AB - The receptors for VIP and PACAP were characterized in vitro on rat ileal and colonic longitudinal smooth muscle with adherent myenteric ganglia. Colon strips from PAC1 receptor knockout and wildtype mice were also examined. VIP, PACAP-38 and PACAP-27 all caused concentration dependent relaxations. In rat ileum three different types of smooth muscle VIP/PACAP receptors were defined: (1) a PACAP-27 preferring receptor coupled to apamin sensitive Ca(2+)-dependent K+ channels, (2) a PAC1 receptor activated by both PACAP-27 and PACAP-38, and (3) a VIP specific receptor regulated by NPY. The receptors identified in rat colon were: (1) a PAC1 receptor localized on NO synthesizing neurones. Activation leads to increased NO production. (2) A smooth muscle PAC1 receptor. The responses elicited by both receptors were abolished by apamin. (3) A smooth muscle VIP specific receptor. PAC1 receptor knockout mice did not respond to PACAP-27 or PACAP-38, whereas VIP induced a relaxatory response indicating the presence of a VIP specific receptor. In wildtype mice all three peptides elicited relaxatory responses. Pharmacological characterization of intestinal VIP/PACAP receptors indicates the existence of receptors, such as a PACAP-27 preferring receptor and a VIP specific receptor, distinct from those that have been cloned (VPAC1, VPAC2, and PAC1). PMID- 11193818 TI - Mutational analysis of the glucose regulatory element in the promoter of the glucagon receptor gene. AB - Recently, we identified a glucose regulatory element in the promoter of the rat glucagon receptor gene. The effect of glucose is centered on a highly palindromic sequence of 19 nucleotides that we called the G box (Portois et al., 1999, J. Biol. Chem. 274: 8181-8190). This sequence contains two E boxes. Recently, we investigated the role of each individual E box, as well as the contribution of the sequences located upstream and downstream from this G box. (1) Mutation of nucleotides "CA" to "GT" in the first E box (position -543 to -542) suppressed the activation of the CAT reporter gene by glucose. In contrast, mutation of the nucleotides "CA" to "GT" in the second E box (position -534 to -533) had no effect on this glucose activation. (2) Deletion of a sequence upstream from the G box (nucleotides -579 to -555) suppressed the activation by glucose, whereas deletion of a sequence located downstream from the G box (nucleotides -501 to 443) had no effect on this parameter. (3) Subcloning of a small promoter fragment of only 49 nucleotides (-560 to -512) into the pCat5 plasmid conferred to transfected cells sensitivity to glucose in terms of CAT activity. Consequently, all transactivation factors required for this glucose effect must act via this short gene fragment. PMID- 11193819 TI - Molecular characterization of the VIP receptor transcriptional repressor protein. AB - The rat type 1 VIP receptor transcriptional repressor protein (VIPR-RP) is a recently isolated novel transcription factor. In the study reported here, the functional domains of VIPR-RP were characterized. To map the DNA binding domain, various regions of VIPR-RP were either transcribed and translated in vitro or expressed in and purified from E. Coli as a glutathione S-transferase (GST) fusion. The ability of the truncated proteins to bind to VIPR-RP specific binding sequence was tested by gel mobility shift assays. The results indicated that the amino acid sequences between 367 and 475 play an essential role for VIPR-RP DNA binding. To determine the amino acid sequences required for transcriptional repression, fusion proteins containing the GAL4 DNA binding domain and various parts of VIPR-RP were constructed, and their ability to repress transcription of the reporter gene containing GAL4 DNA binding sequences were tested in transiently transfected COS7 cells. The results showed that VIPR-RP contains two separate transcriptional repression domains located between amino acids 50 to 101 and 470 to 527. PMID- 11193820 TI - Regulation of vasoactive intestinal peptide receptor expression in developing nervous systems. AB - Vasoactive intestinal peptide (VIP) is a 28-amino acid peptide that has several functions, including the regulation of water and electrolyte secretion, hormone and cytokine release, bronchodilitation, and neurogenesis. VIP effects are mediated by specific G-protein coupled receptors. Three distinct receptor subtypes, with differing affinity for VIP, have been cloned and characterized as receptors 1 and 2 (VPAC1 and VPAC2) and pituitary adenylate cyclase activating polypeptide receptor (PAC1). Our laboratory has demonstrated that upregulation of VPAC1 in SK-N-SH neuroblastoma cells results in marked shift in cell type to the glial lineage with a corresponding loss of neuronal lineage and suppression of xenograft tumor growth. To understand the molecular mechanisms responsible for regulation of the VPAC1 gene in neuronal lineage, we have cloned and sequenced 2.6-kb of the 5'-flanking sequences of the human VPAC1 gene. Sequence analysis demonstrated that the human VPAC1 promoter sequence contains putative binding sites for several known transcription factors, including Sp1, NFkB, and cETS-1. To study the temporal and spatial expression pattern of human VPAC1 promoter sequences, we have generated transgenic mice expressing the bacterial beta galactosidase gene under the control of the 2.6-kb 5'-flanking and promoter sequence of the human VPAC1 gene. Transgene expression was detected in brain, spinal cord, and lung in 14-day-old animals. Taken together, these results demonstrate that VPAC1 may play an important role in the nervous system, and suggest a role for VIP in neuronal differentiation. PMID- 11193821 TI - Differential activation of phospholipase D by VPAC and PAC1 receptors. AB - To investigate the phospholipase D (PLD) responses of the VIP/PACAP receptors, VPAC1 and VPAC2, and the PACAP-specific PAC1 receptors (short and "hop" intracellular loop 3 (i3) splice variants), stable CHO cell lines expressing similar levels of each wildtype receptor were generated (except for the VPAC1 receptor clone which showed considerably lower expression and lesser responses in signalling assays). All clones caused activation of PLD in response to agonists, as monitored by [3H]phosphatidylbutanol production. The PLD responses of the PAC1 "hop", but not the "null" receptor, were sensitive to the ARF inhibitor, brefeldin A (BFA) (as were VPAC1 and VPAC2 responses). Chimeric constructs of VPAC2 receptors containing i3 of either PAC1 hop or PAC1 null receptors were transiently expressed in COS 7 cells and PLD responses were measured. Only the PLD response of the hop construct was sensitive to BFA. This suggests that i3 motifs in certain Group II GPCRs may play a key role in determining their linkage to ARF-dependent PLD activation. PMID- 11193822 TI - PACAP modulates rat sympathetic neuron depolarization through IP3. PMID- 11193823 TI - Essential structural motif in the C-terminus of the PACAP type I receptor for signal transduction and internalization. AB - The objectives of the study reported here were to identify amino acid residues of the C-terminus that are critical for intracellular signaling. A total of nine amino acid substitution and truncation mutants were constructed by PCR and confirmed by sequencing. Mutant and wildtype receptors were stably transfected into NIH/3T3 fibroblasts and studied for their ability to bind PACAP-27 and activate phospholipase C (PLC) and adenylyl cyclase (AC). Receptor affinity of 125I-PACAP-27 for the wildtype and mutants were similar (Kd = 0.6-1.5 nM). However, truncation of the entire 63 amino acids of the hPAC1 resulted in no signaling to either AC or IP. Addition of the proximal 10 amino acids of the C terminus failed to restore AC or IP signaling, whereas addition of the proximal 27 amino acids of the C-terminus resulted in reconstitution of complete AC and IP responses, identical to the WT. Point mutations within this 17 amino acid region identified specific amino acids involved in PAC1 signaling. These results indicate that a structural motif within the proximal region of the carboxyl terminus is critical for G protein coupling. PMID- 11193824 TI - PACAP peptides modulate guinea pig cardiac neuron membrane excitability and neuropeptide expression. AB - Morphological studies identified PACAP-immunoreactive nerve fibers in dense pericellular arrangements around virtually every cholinergic parasympathetic neuron of guinea pig cardiac ganglia; all postganglionic cardiac neurons expressed membrane-associated PAC1 receptor protein. Characterization of the alternative splice variants established predominant expression of the PAC1(very short) receptor transcript containing neither HIP nor HOP exons. PACAP depolarized cardiac neurons and increased membrane excitability; the excitability resulted from neither altered action potential properties nor inhibition of IM. Treatment of cardiac ganglia explants with PACAP significantly reduced the numbers of cholinergic neurons coexpressing somatostatin immunoreactivity, which did not appear to be correlated with prosomatostatin mRNA expression. The PACAP mediated decrease in somatostatin immunoreactive neurons required calcium influx through L-type calcium channels and activation of adenylyl cyclase, whereas activation of phospholipase C or protein kinase A was not required. These observations indicate that PACAP through the PAC1 receptors elicits complex actions on guinea pig parasympathetic cardiac ganglia neurons, including modulation of membrane ion conductances and modulation of neuropeptide expression. PMID- 11193825 TI - Functional significance of colocalization of PACAP and catecholamine in nerve terminals. AB - Medullary neurons containing pituitary adenylate cyclase-activating polypeptide (PACAP) and noradrenalin (NA) project to the hypothalamus and they are involved in the regulation of arginine vasopressin (AVP) neurons. At the ultrastructural level, PACAP immunoreactivity was detected in the granular vesicles in catecholaminergic nerve terminals that made synaptic contact with AVP neurons. Both PACAP (at least 1 nM) and NA (at least 1 microM) induced large increases in the cytosolic Ca2+ concentration ([Ca2+]i) in isolated AVP cells. PACAP at 0.1 nM and NA at 0.1 microM had little effects, if any, on [Ca2+]i. However, when 0.1 nM PACAP and 0.1 microM NA were combined, they evoked large increase in [Ca2+]i in AVP neurons. An inhibitor of protein kinase A (PKA) completely inhibited the PACAP-induced increase in [Ca2+]i, but only partly inhibited the NA-induced increase in [Ca2+]i. In AVP cells that were prelabeled with quinacrine, PACAP and NA acted synergistically to induce a loss of quinacrine fluorescence, indicating secretion of neurosecretory granules in AVP neurons. The results suggest that PACAP and NA, coreleased from the same nerve terminals, act in synergy to evoke calcium signaling and secretion in AVP neurons, and that the synergism is mediated by the interaction between cAMP-PKA pathway an as yet unidentified factor "X" linked to L-type Ca2+ channels. The synergism between PACAP and NA may contribute to the regulation of AVP secretion under physiological conditions. PMID- 11193826 TI - VIP- and PACAP-induced salivary chromogranin A secretion in the isolated perfused submandibular gland of rats. AB - In the study reported in this paper, sensitive ELISA for rat CgA was developed using synthetic rat CgA(359-389) as antigen, N alpha-biotinylated glycylglycyl rat CgA(359-389), and antirat CgA(359-389) serum for the measurement of CgA-LI in rat saliva. CgA-LI in rat submandibular tissues and saliva was characterized by both immunohistochemical and immunochemical methods. Using isolated perfused rat submandibular gland. VIP at 0.1-1.0 nM in the presence of 0.1 microM ACh was found to cause CgA-LI secretion, whereas neither PACAP-27 nor PACAP-38 showed any effect on CgA secretion. PMID- 11193827 TI - New developments in the biology of the glucagon-like peptides GLP-1 and GLP-2. AB - Glucagon-like peptides 1 and 2 (GLP-1 and GLP-2) are coencoded within a single mammalian proglucagon precursor, and are liberated in the intestine and brain. GLP-1 exerts well known actions on islet hormone secretion, gastric emptying, and food intake. Recent studies suggest GLP-1 plays a central role in the development and organization of islet cells. GLP-1 receptor signaling appears essential for beta cell signal transduction as exemplified by studies of GLP-1R-/- mice. GLP-2 promotes energy assimilation via trophic effects on the intestinal mucosa of the small and large bowel epithelium via a recently cloned GLP-2 receptor. The actions of GLP-2 are preserved in the setting of small and large bowel injury and inflammation. The biological actions of the glucagon-like peptides suggest they may have therapeutic efficacy in diabetes (GLP-1) or intestinal disorders (GLP 2). PMID- 11193828 TI - Role of PACAP1 receptor in regulation of ECL cells and gastric acid secretion by pituitary adenylate cyclase activating peptide. AB - We previously reported that PAC1 is expressed on ECL cells resulting in stimulation of [Ca2+]i, histamine and acid secretion. The study reported here characterized the signaling by PAC1 on ECL cells; determined the effects of PACAP on the gastric acid secretion in vivo, and determined the effects of chronic administration of PACAP-27 on ECL cell proliferation. PACAP-27 dose dependently stimulated ECL cell Ca2+ and AC with detectable stimulation at 1 nM and maximal stimulation at 100 nM (six-fold). In rats PACAP-27 administration (10 pmol/kg/h) increased the rate of gastric acid secretion when an antisomatostatin antibody was co-administered. Chronic administration of PACAP (10 pmol/h for seven days) via osmotic pump resulted in a more than twofold increase in BrdU incorporation into ECL cells. PACAP acting at the PAC1 results in dual signaling responses to both [Ca2+]i. AC in ECL cells stimulates gastric acid secretion via the actions of histamine acting at the parietal cell and in whole animals leads to proliferation of ECL cells when administered chronically. PMID- 11193829 TI - Integrative mitogenic role of protein kinase B/Akt in beta-cells. AB - Protein kinase B/Akt (PKB/Akt) is activated by phosphatidylinositol 3-kinase (PI 3-K) and is a central mediator of cellular proliferation and protection against apoptosis. Insulin, insulin-like growth factor (IGF-1), and glucagon-like peptide 1 (GLP-1) act as glucose-dependent growth factors for pancreatic beta-cells. We assessed signaling pathways and stimulation patterns of PKB/Akt activation by these ligands in the beta-cell line INS-1. Insulin, IGF-1, and GLP-1 induced distinctive time dependent, dose dependent, and glucose dependent phosphorylation of PKB/Akt. Insulin and IGF-1 stimulated PI 3-K activity was mainly associated with insulin receptor substrate (IRS) isoforms IRS-1 and IRS-2 and less so with the IRS-isoform Grb-2 associated binder-1 (Gab-1). In contrast, GLP-1 induced PI 3-K activity mainly in Gab-1 and also in IRS-2 immunoprecipitates, although in an attenuated kinetic. Thus, activation pathways of PKB/Akt by insulin, IGF-1, and GLP-1 converge at the level of IRS-isoforms and PI 3-K inducing differential activation of PKB/Akt. These data indicate an essential role of PKB/Akt in regulation of beta-cell proliferation. PMID- 11193830 TI - The effects of PACAP on insulin secretion and glucose disposal are altered by adrenalectomy in mice. AB - We previously showed that pituitary adenylate cyclase-activating polypeptide (PACAP) potently stimulates insulin secretion in vivo in mice without altering glucose disposal. Such a combination of results would be explained if epinephrine released by PACAP counteracts the action of insulin and, therefore, that the glucose disposal after PACAP administration is altered by adrenalectomy. In the study reported in this paper, we examined the influence of PACAP27 (1.3 nmol/kg i.v.) on insulin secretion and glucose disposal during an intravenous glucose (1 g/kg) tolerance test in mice subjected to bilateral adrenalectomy 48 h prior to the tolerance test. We found that in control mice, PACAP potentiated glucose stimulated insulin secretion threefold without affecting glucose disposal. Adrenalectomy potentiated the augmentation by PACAP27 of glucose-stimulated insulin secretion, and in adrenalectomized mice, PACAP27 simultaneously augmented glucose disposal (elimination rate 2.30 +/- 0.07%/min vs. 2.56 +/- 0.05%/min; p = 0.011). Furthermore, PACAP27 augmented glucose elimination stimulated by i.v. insulin administration only in adrenalectomized, but not in control mice. We, therefore, conclude that under in vivo conditions, epinephrine released by PACAP from the adrenals prevents the marked insulinotropic action of the peptide from augmenting glucose disposal. PMID- 11193831 TI - Intraperitoneal PACAP administration decreases blood glucose in GK rats, and in normal and high fat diet mice. AB - PACAP is an islet peptide that serves as an endogenous amplifier of glucose induced insulin secretion. Furthermore, we has recently found that PACAP also potentiates insulin stimulated glucose uptake in adipocytes. Therefore, an antidiabetic action of PACAP is possible. In the present study, we examined the effect of PACAP treatment of the hyperglycemia in GK rats, an animal model of type 2 diabetes, and in high fat fed C47BL/6J mice, an animal model for glucose intolerance. GK rats housed with normal diet exhibited a normal level of blood glucose until three weeks old but significant hyperglycemia at eight weeks. When GK rats were treated with daily PACAP38 (i.p. injection, 6 pmol/kg) from age three weeks, development of hyperglycemia was prevented. In high fat fed mice, i.p. administration of PACAP27 for five (25 nmol/kg twice daily) reduced plasma glucose levels to 6.9 +/- 0.2 mmol/l compared to 8.1 +/- 0.2 mmol/l in saline injected animals (p < 0.001) without altering baseline insulin levels. We conclude that PACAP reduces circulating glucose in animal models of type 2 diabetes and glucose intolerance. The mechanism of this action needs to be established. PMID- 11193832 TI - VPAC1 receptors and lung cancer. AB - VIP/PACAP are autocrine growth factors for lung cancer. VIP and/or PACAP mRNA is present in most lung cancer cell lines examined. Although mRNA for VPAC2-R is not common, VPAC1-R and PAC1-R mRNA is present in many lung cancer cell lines. 125I VIP binds with high affinity to lung cancer cells and specific 125I-VIP binding is inhibited with high affinity by (Lys15, Arg16, Leu27)VIP1-7 GRF8-27, the VPAC1 R specific agonist, but not by Ro25-1553(18), the VPAC2-R specific agonist. VIP elevates cAMP and increases c-fos gene expression. The increase in cAMP and c-fos mRNA caused by VIP is inhibited by SN(VH). (SH)VH inhibited the proliferation of NCIH1299 cells in the MTT assay, which is based on cytotoxicity. In a recent cell line screen, (SN)VH inhibited the growth of 51 of 56 cancer cell lines including leukemia, lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, breast cancer, and prostate cancer (T. Moody, unpublished). It remains to be determined if (SN)VH will be useful for treatment of a wide variety of cancers. PMID- 11193833 TI - The Viktor Mutt Memorial Lecture. Protection by VIP and related peptides against cell death and tissue injury. PMID- 11193834 TI - Cyanine dye labeled vasoactive intestinal peptide and somatostatin analog for optical detection of gastroenteropancreatic tumors. PMID- 11193835 TI - Analysis of VIP and CGRP plasma levels after radiotherapy for treatment of metastasis from prostatic carcinoma. AB - It has previously been shown that radiotherapy leads to an increased level of neuropeptides in various organs. In the study we report here, we examined whether the plasma levels of two neuropeptides, vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP), are influenced by radiotherapy. Blood was collected at four time intervals after radiotherapy; 1-12 days after treatment for skeletal metastasis from prostatic carcinoma. The VIP- and CGRP-plasma levels, as analyzed by radioimmunoassay, were not statistically different between the different time points analyzed. PMID- 11193836 TI - Anti-inflammatory actions of VIP/PACAP. Role in endotoxemia. PMID- 11193837 TI - The effect of cardiac arrest on the permeability of the mouse blood-brain and blood-spinal cord barriers to PACAP. PMID- 11193838 TI - PACAP acts as a neurotrophic factor during histogenesis of the rat cerebellar cortex. AB - During development of the rat cerebellum, PAC1 receptors are transiently expressed by neuroblasts of the external granule cell layer (EGL). We have previously shown that PACAP is a potent stimulator of granule cell survival in vitro. In the study reported in this paper, we have investigated the effect of PACAP on the development of the rat cerebellar cortex in vivo. PACAP induces a transient increase in the volume of the cerebellar cortex, with a maximum effect at postnatal day 12, which can be accounted for by an increase in the number of granule cells in the EGL, the molecular layer, and the internal granule cell layer (IGL). The effect of PACAP on the number of granule cells is blocked by the antagonist PACAP(6-38), which, by itself, produces a slight inhibition of the number of granule cells in the IGL. These data indicate that PACAP activates proliferation and/or inhibits programmed cell death of granule cells in the developing rat cerebellum. PACAP also stimulates neuronal migration from the EGL to the IGL. Thus, it appears that PACAP can act in vivo as a neurotrophic factor controlling histogenesis of the cerebellar cortex. PMID- 11193839 TI - Molecular cloning, mRNA distribution and pharmacological characterization of a VIP/PACAP receptor in the frog Rana ridibunda. PMID- 11193840 TI - Distribution of PACAP receptor mRNAs and PACAP binding sites in the rat brain during development. PMID- 11193841 TI - Immunohistochemical and immunochemical evidence for expression of human lung PACAP/VIP receptors. PMID- 11193842 TI - Expression and coupling of PACAP/VIP receptors in cortical neurons and type I astrocytes. PMID- 11193843 TI - Ultrastructural localization of PACAP immunoreactivity in the rat retina. PMID- 11193844 TI - PACAP and VIP in the photoneuroendocrine system. From the retina to the pituitary gland. PMID- 11193845 TI - Synaptic interaction between galanin immunoreactive neurons and axon terminals immunopositive for VIP and PACAP in the bed nucleus of the stria terminalis in the rat. PMID- 11193846 TI - Downregulation of VPAC1R expression in breast cancer cell lines. AB - The breast carcinoma cell line T47D was tested for 17 beta-estradiol (E2) mediated regulation of vasoactive intestinal polypeptide receptor type-1 (VPAC1) expression. E2 was found to downregulate the mRNA level. The number of VIP binding sites was reduced 66% on treatment with E2 for 72 h. Experiments with cycloheximide suggested that the effect was independent (at least partly so) of protein synthesis. Experiments with the transcriptional inhibitor, actinomycin D, showed that E2 did not influence the VPAC1 mRNA halflife. Both of two antiestrogens, ICI 182,780 and 4-hydroxy-tamoxifen, mediated a concentration dependent inhibition of the effect of E2 on the mRNA level. Transient transfection with reporter-gene constructs containing various portions of the VPAC1 5'-flanking sequence revealed the most proximal 100 bp to be essential for the basal transcriptional activity. However, E2 did not influence the expression of the reporter gene using up to 3,250 bp of the VPAC1 5'-flanking region. PMID- 11193847 TI - Prohormone convertase PC4 processes the precursor of PACAP in the testis. PMID- 11193848 TI - Presence of PACAP-immunoreactive neurons in the trigeminal ganglion of the sheep. Indications for a trigeminal innervation of the pineal gland. PMID- 11193849 TI - Genomic organization and chromosomal localization of the mouse pituitary adenylate cyclase activating polypeptide (PACAP) gene. PMID- 11193850 TI - PACAP receptor expression in the rat adrenal medulla by in situ hybridization and immunocytochemistry. PMID- 11193851 TI - Alanine scanning of VIP. Structure-function relationship for binding to human recombinant VPAC1 receptor. PMID- 11193852 TI - Postnatal development of vasoactive intestinal peptide receptor-effector system in rat immunocompetent cells. PMID- 11193853 TI - Sequences (103-110) and (116-120) of the rat secretin receptor are implicated in secretin and VIP recognition. PMID- 11193854 TI - Gene expression for PACAP receptor mRNA in the rat retina by in situ hybridization and in situ RT-PCR. PMID- 11193855 TI - Imaging tumors in humans with Tc-99m-VIP. AB - Vasoactive intestinal peptide (VIP) was modified at the C terminus with a spacer and four amino acids to serve as a chelating moiety. The modified peptide, TP 3654, was labeled with Tc-99m and evaluated in normal volunteers, as well as in patients with a history of cancer. Renal clearance (67%) was the primary route of excretion, with approximately 20% of the radioactivity clearing through the hepatobiliary system. No adverse reaction was noted in any of the subjects and all, except one small, of the known lesions as seen by CT, MRI, Tc-99m-MIBI, or mammography were correctly identified within a few minutes of an i.v. injection of approximately 10 mCi of Tc-99m-TP 3654 (specific activity 11.3 x 10(3) Ci/m mol). The scans were in concordance in nine patients. In the remaining two, one with a visible mass in the neck from high grade spindle cell sarcoma and the other with a palpable mass in a breast from ductal epithelial hyperplasia, were localized only with Tc-99m-TP 3654, but not with Tc-99m-MIBI. Both malignancies are known to express VIP receptors. The VIP analog promises to be a nontoxic and reliable agent for imaging cancers in humans that express VIP receptors. PMID- 11193856 TI - Organization of the rat PACAP gene. AB - The rat PACAP gene has been isolated, cloned, and sequenced. The gene organization is very similar to that of the mouse and human PACAP genes. An analysis of the 5'-UTR in proPACAP mRNAs indicates that multiple transcripts are generated by using different splice sites within exons 1A, 1B, and 2 to form the 5'-UTR. Analysis of PACAP promoter activity in PC12 cells suggests that forskolin responsiveness of the gene is dependent on elements located between -77 and -413 bp from the transcription start site. PMID- 11193857 TI - Distribution of PACAP receptor and its splice variants in the rat brain by in situ RT-PCR. PMID- 11193858 TI - Ontogeny of PACAP receptor and its splice variants in the rat brain. PMID- 11193859 TI - Effect of flutamide androgen-receptor blockade on rat prostatic VIP receptor/effector system. PMID- 11193860 TI - Dual contacts between peptide agonist ligands and the secretin receptor directly established by photoaffinity labeling. AB - Structural analysis of secretin in solution has demonstrated extended helical domains within both amino- and carboxyl-terminal halves, with a possible turn in between. However, the conformation of this peptide as it resides in its binding site within the receptor has not been established. In the work reported here, we performed affinity labeling of the secretin receptor with radioiodinated secretin analogues having photolabile benzoyl-phenylalanine residues positioned in each half of the peptide. The probes had sites of covalent attachment in positions 6 and 22, and have been recently synthesized and characterized to represent high affinity agonist ligands. Both covalently labeled the secretin receptor in a saturable, specific, and efficient manner. After purification of the labeled receptor, we used a series of chemical and enzymatic cleavage techniques to define the domain of labeling. We complemented this by receptor mutagenesis, followed by additional cleavage and Edman degradation sequencing to refine our insights into the labeled residues. This has allowed us to demonstrate that sites of attachment were both within the extracellular aminoterminal domain of the receptor. Of particular interest, both probes labeled residues within the amino terminal thirty residues at the distal end of the receptor. It will be particularly interesting to use these molecular approximations to model the binding domain of this important receptor. PMID- 11193861 TI - VIP regulates angiotensinogen synthesis in the liver. PMID- 11193862 TI - Nerve growth factor upregulates the PAC1 promoter by activating the MAP kinase pathway in rat PC12 cells. AB - We report that: (1) An increase in the transcription activity is a mechanism by which trophic peptides may regulate the expression of PAC1. (2) An activation of the PAC1 promoter does not necessarily correlate with the neurotrophin-promoted neuritogenesis. (3) Activation of the PAC1 promoter is probably an early event since the EGF response is rather weak and transient in PC12 cells. (4) MAP kinase pathway activation is necessary for the NGF effect. The mechanism of the antagonism between PACAP and NGF observed on the PAC1 promoter activity and already described in regulating chromaffin cell proliferation, remains to be explained. PMID- 11193863 TI - Different domains of the VIP receptors modulate agonist affinity and intrinsic activity. PMID- 11193864 TI - PAC1 null females display decreased fertility. AB - We report here that PAC1 KO females display decreased fertility, whereas male fertility was normal. ICC on pituitary section showed that FSH, LH, and prolactin synthesis were not affected in KO mice. Moreover, the pituitary-gonadal axis responded properly to an acute fasting test in KO mice. Hence, the phenotype of PAC1 null mice provides clear evidence for the role of PAC1 receptor in reproduction process. PMID- 11193865 TI - The inhibitory effect of PACAP38 on ovulation is mediated by CRF and endogenous opioids. PMID- 11193866 TI - PACAP and VIP induce changes in cytosolic calcium in putative folliculostellate cells of the mouse pituitary. PMID- 11193867 TI - PACAP augments nitric oxide synthesis in rat vascular smooth muscle cells stimulated with IL-1 alpha. PMID- 11193868 TI - Synergistic interaction between VIP-related peptides and bombesin on ion transport in guinea pig distal colonic mucosa. PMID- 11193869 TI - The effect of VIP on progesterone (PROG) release in dehydrated male rats. PMID- 11193870 TI - Occurrence and effect of PACAP in the human fetal adrenal gland. AB - In the study reported in this paper, we characterized PACAP in the human fetal adrenal gland and we investigated the effect of PACAP on steroid secretion from cultured fetal adrenal cells. The adrenal gland from 20-week-old fetuses contained substantial concentrations of PACAP-immunoreactive material (88.6 ng/g wet tissue). HPLC analysis of adrenal extracts revealed the presence of both PACAP27 and PACAP38, the latter being the predominant form. Incubation of cultured fetal adrenal cells with PACAP38 (10(-7) M) significantly increased cortisol and DHEAS secretion. Administration of the beta-adrenoreceptor agonist isoproterenol mimicked the stimulatory effect of PACAP on both steroid secretion whereas preincubation of fetal cells with the beta-adrenoreceptor antagonist propranolol suppressed the steroidogenic effect of PACAP. These data, together with the observation that PACAP receptors are exclusively located on chromaffin cells, suggest that, in the fetal human adrenal gland, the effect of PACAP on steroid secretion is mediated via the local release of catecholamines. PMID- 11193871 TI - Distribution of vasoactive intestinal polypeptide and its effect on glucagon secretion from normal and diabetic pancreatic tissue fragments in rat. PMID- 11193872 TI - PACAP activates pancreatic alpha-cells in a glucose independent manner. PMID- 11193873 TI - The role of VIP and somatostatin in the control of GH and prolactin release in anorexia nervosa and in obesity. PMID- 11193874 TI - Vasoactive intestinal peptide (VIP) receptor type 2 (VPAC2) is the predominant receptor expressed in human thymocytes. AB - Vasoactive intestinal peptide (VIP) binding sites have been identified in the human thymus, but the receptor subtype and how these receptors are distributed in the human thymus subsets is unknown. To assess gene expression, distribution, and receptor regulation of the two G-protein-associated VIP receptors, VPAC1 and VPAC2 mRNAs were quantified using a novel fluorometric-based kinetic (real-time) RT-PCR. Bulk and fractionated thymocytes were stimulated via the TCR/CD3 receptor complex and anti-CD28. Our results demonstrate that thymocytes express higher levels of VPAC2 compared to VPAC1 expression in bulk thymocytes, CD4+CD8+ selected double positives (DP), and CD8 depleted thymocytes. Double negative cells express low levels of VPAC2 mRNA. We demonstrate T-cell activation dependent down-regulation of VPAC1, but not VPAC2, in human thymocytes. This study reports the first direct evidence of a differential distribution and selective regulation of VPAC1 and VPAC2 gene expression in normal human thymocyte subsets. PMID- 11193875 TI - PACAP27 sensitizes glucose induced insulin secretion in INS-1 cells. PMID- 11193876 TI - Distinctive effects of glicentin, GLP-1 and GLP-2 on adaptive response to massive distal small intestine resection in rats. PMID- 11193877 TI - Cytosolic calcium handling in islets of normal Wistar and diabetic Goto Kakizaki rats in the presence of glucose and truncated glucagon-like peptide 1 (7-36) amide. PMID- 11193878 TI - Colocalization of GLP-1 and GIP in human and porcine intestine. PMID- 11193879 TI - Insulinotropin PACAP potentiates insulin action. Stimulation of glucose uptake in 3T3-LI adipocytes. AB - PAC1 receptor was expressed in the rat fat tissue and 3T3-L1 adipocytes. PACAP-38 (10 nM) significantly enhanced insulin induced 2-deoxyglucose uptake by 3T3-L1 adipocytes. GLP-1 has a similar effect. PACAP-38 further increased insulin stimulated phosphatidylinositol (PI) 3-kinase activity, but has not effect on tyrosine phosphorylation of insulin receptor beta-subunit or IRS-1. These results reveal that PACAP-38 enhances insulin induced glucose uptake, an effect probably mediated by PI 3-kinase. In conclusion, PACAP potentiates not only insulin secretion but also insulin action in adipocytes, thereby exhibiting antidiabetic actions at two important steps of glucose metabolism (Fig. 2). PMID- 11193880 TI - VIP and PACAP inhibit activation induced apoptosis in T lymphocytes. AB - Apoptosis in T and B lymphocytes is a major element controlling the immune response. Activation induced cell death (AICD) in T cells is a main mechanism for maintaining peripheral tolerance and for limiting an ongoing immune response. AICD is initiated by antigen reengagement of the T cell receptor (TCR), and mediated through Fas/Fas ligand (FasL) interactions. VIP and PACAP are two multifunctional neuropeptides present in the lymphoid microenvironment that act primarily as anti-inflammatory agents. In this study we report on the role of VIP and PACAP on T cell AICD, and on the mechanisms involved. VIP and PACAP inhibit AICD in vivo and in vitro, in peripheral T cells and T cell hybridomas. The effect is dose dependent and is mediated through the specific receptors VPAC1 and VPAC2. The inhibition of AICD is achieved through reduction in FasL expression at protein and mRNA level. By affecting FasL expression, VIP and PACAP may play a physiological role in both the generation of memory T cells and the inhibition of FasL-mediated T cell cytotoxicity. PMID- 11193881 TI - VIP and PACAP induce shift to a Th2 response by upregulating B7.2 expression. AB - VIP and PACAP, two structurally related neuropeptides produced within the lymphoid microenvironment, modulate several immunological functions. Although primarily anti-inflammatory in nature, VIP and PACAP also affect resting macrophages. In this study, we report on the role of VIP and PACAP on macrophage B7 expression and costimulatory function for antigen-primed CD4+ T cells, and on the macrophage-induced regulation of Th1/Th2 differentiation in vitro and in vivo. VIP and PACAP upregulate B7.2, but not B7.1, MHC class II, or ICAM-1 expression, and activate macrophages to stimulate the proliferation of naive T cells in response to soluble anti-CD3 or allogeneic stimulation. The stimulatory effect is mediated through the specific receptor VPAC1, and involves the cAMP/PKA pathway as second messengers. The enhancement in B7.2 expression occurs at both mRNA and protein levels, and correlates with the VIP/PACAP induced upregulation of the costimulatory activity of macrophages for antigen-primed CD4+ T cells. VIP/PACAP-treated macrophages gain the ability to induce Th2-type cytokines such as IL-4 and IL-5, and to reduce Th1-type cytokines such as IFN gamma and IL-2. In vivo administration of VIP or PACAP in antigen-immunized mice reduces the numbers of IFN gamma-secreting cells, enhances the numbers of IL-4-secreting cells, and affects the pattern of antigen-specific Ig isotypes. The preferential differentiation into Th2 effector cells induced by VIP/PACAP-treated macrophages is mediated through the upregulation of B7.2 expression. Since Th1-dominated responses are associated with some autoimmune diseases and inflammatory reactions typical of cell-mediated immunity, the VIP/PACAP inhibition of Th1 development may represent an additional mechanism for the general anti-inflammatory activity of the two neuropeptides. PMID- 11193882 TI - Vasoactive intestinal peptide mediation of development and functions of T lymphocytes. AB - The first phase in investigating neural regulation of immunity has delineated anatomical connections, shared mediators and receptors for mediators with distinctive effects, and the immune functional consequences of altering relevant neural activities. Vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase-activating peptide (PACAP) are represented prominently in immune organs. They have potent novel effects on many aspects of immunity, are derived from and serve as autacoids in some sets of immune cells, and they participate in both physiological and pathological immune responses. The present phase of neuroimmune research has begun to elucidate the genetic determinants of expression and functions of neuromediators in immunity. Our evolving understanding of the novel mechanisms for adaptation and specificity in the VIP/PACAP neuroimmune network suggests the importance of immunoselective transcriptional control of expression of VIP/PACAP receptors in T cells, a dominant role for numerous cytokines, and the critical involvement of small subsets of VIP-/PACAP-responsive thymocytes and T cells. PMID- 11193883 TI - Receptors and transcriptional factors involved in the anti-inflammatory activity of VIP and PACAP. AB - VIP and PACAP modulate the function of inflammatory cells through specific receptors. VIP/PACAP inhibit the production of TNF alpha, IL-6, IL-12, and nitric oxide (NO), and stimulate IL-10 in peritoneal macrophages and Raw 264.7 cells. Here we report on the specific VIP/PACAP receptors, transduction pathways, and transcriptional factors involved in the regulation of these macrophage factors by VIP and PACAP. Both neuropeptides inhibit IL-6 production mainly through PAC1 binding, PKC activation, and the subsequent shedding of the LPS receptor CD14 in macrophages. However, the effects on TNF alpha, IL-10, IL-12, and NO are mostly mediated through the constitutively expressed VPAC1 receptor, although the inducible expressed VPAC2 may also participate. VIP/PACAP binding to VPAC1 induces both a cAMP-dependent and a cAMP-independent pathways that regulate cytokine and NO production at the transcriptional level. VIP/PACAP inhibit TNF alpha through reduction in NFkB binding and changes in the composition of CRE binding complexes; they inhibit IL-12 through reduction in NFkB binding and changes in the composition of the ets-2 complexes. VIP/PACAP inhibit iNOS expression through reduction in NFkB and IRF-1 binding, and augment IL-10 by increasing CREB-binding. Whereas the inhibition of IRF-1 and CRE-binding complexes seems to be mediated through the cAMP-dependent pathway, VIP/PACAP inhibition of NFkB nuclear translocation is mediated through a reduction in IkB alpha degradation mediated by the cAMP-independent pathway. This study provides new evidence for the understanding of the molecular mechanism by means of which VIP and PACAP attenuate the inflammatory response. PMID- 11193884 TI - Mechanism of action of camptothecin. AB - Camptothecin (CPT) class of compounds has been demonstrated to be effective against a broad spectrum of tumors. Their molecular target has been firmly established to be human DNA topoisomerase I (topo I). CPT inhibits topo I by blocking the rejoining step of the cleavage/religation reaction of topo-I, resulting in accumulation of a covalent reaction intermediate, the cleavable complex. The primary mechanism of cell killing by CPT is S-phase-specific killing through potentially lethal collisions between advancing replication forks and topo-I cleavable complexes. Collisions with the transcription machinery have also been shown to trigger the formation of long-lived covalent topo-I DNA complexes, which contribute to CPT cytotoxicity. Two novel repair responses to topo-I mediated DNA damage involving covalent modifications of topo-I have been discovered. The first involves activation of the ubiquitin/26S proteasome pathway, leading to degradation of topo-I (CPT-induced topo-I downregulation). The second involves SUMO conjugation to topo-I. The potentials roles of these new mechanisms for repair of topo-I-mediated DNA damage in determining CPT sensitivity/resistance in tumor cells are discussed. PMID- 11193885 TI - Homocamptothecins: E-ring modified CPT analogues. AB - Homocamptothecins (hCPT) are modified camptothecins (CPT) with a seven-membered beta-hydroxylactone instead of the naturally occurring six-membered alpha hydroxylactone. This E-ring modification fully conserves the ability to stabilize topo I-DNA single-strand breaks and stimulates high levels of DNA cleavage. A key feature is the irreversibility of E-ring opening, which should give reduced toxicity. Substituted hCPTs have been selected for their high antiproliferative activity on a panel of tumor cell lines, including those with cross resistance, and were found to be active at very low doses in a variety of human tumor xenografts when administered orally. BN 80915, a difluoro-hCPT, has entered clinical trials. PMID- 11193886 TI - Molecular and biological determinants of the cytotoxic actions of camptothecins. Perspective for the development of new topoisomerase I inhibitors. AB - Camptothecin, originally discovered in 1957 as an antitumor activity in plant extracts, has recently become one of the most promising leads to new anticancer drugs. After lingering for many years, interest in camptothecin was revitalized in 1985 upon discovery of its specific action on topoisomerase I. Detailed elucidation of action mechanisms at the molecular, cellular, and pharmacologic levels has made camptothecin and its congeners perhaps the best understood among clinical anticancer drugs. Promising chemical variants of camptothecin, and recently other chemical categories of topoisomerase I-targeted drugs, provide unusually rich opportunities for rational drug selection and design. This is made possible by current concepts based, for the most part, on a sound experimental foundation, which points the way towards optimally effective therapy. PMID- 11193887 TI - The cascade radical annulation approach to new analogues of camptothecins. Combinatorial synthesis of silatecans and homosilatecans. AB - An overview of the cascade radical annulation approach to the camptothecin family of antitumor drugs is presented. This combinatorial synthetic approach involves two key steps: (1) N-propargylation of a lactone/pyridone D/E ring fragment and (2) cascade radical annulation of an A-ring isonitrile to form rings B and C. The synthesis is probably the most flexible and general route to the camptothecin class of molecules. The parallel synthesis of several libraries of silatecan and homosilatecan libraries is summarized. One of the first-generation silatecans, DB 67, is emerging as a serious candidate for cancer chemotherapy. PMID- 11193888 TI - Structure-activity relationship of alkyl camptothecin esters. AB - The cytotoxicity of camptothecin (CPT) esters 1-6 was measured. Like parental camptothecin, esters 2 and 3, but not 1, 4, 5, and 6, inhibited proliferation of human leukemia cells in culture and induced programmed cell death as assessed by flow cytometry studies. Exhibition of similar levels of antiproliferative activities of CPT 2 and 3 required different incubation time periods in cell cultures, with CPT and 3 requiring the shortest and longest periods, respectively. Both 2 and 3 were inactive against cells resistant to the semisynthetic CPT derivative 9-nitrocamptothecin and unable to stabilize DNA topoisomerase I (Topo I) "cleavable complexes" in a cell-free system, suggesting that Topo I activity was required but insufficient for the mechanism of action of 2 and 3. Mouse liver homogenate converted esters to parental CPT, but the conversion rates were different with different esters. Of four tested esters in this experiment, ester 2 had the fastest conversion rate. In vivo studies showed that ester 2 had an exceptional lack of toxicity in nude mice, even at enormous doses, and demonstrated extensive activity against human breast and colon tumors grown as xenografts in immunodeficient nude mice, whereas no antitumor activity was observed for the other esters. In conclusion, ester 2 is a prodrug of the antitumor compound CPT, and it can be administered at very high doses in mice with no appearance of toxicity. This study provides a basis for further evaluation of CPT ester 2 as an investigational anticancer agent. PMID- 11193889 TI - Conjugation of camptothecins to poly-(L-glutamic acid). AB - Conjugation of water-insoluble cancer chemotherapeutic drugs to macromolecular polymers can lead to improved pharmaceutical properties and improved therapeutic ratios due to accumulation of the polymer-drug conjugate in tumor tissue through the enhanced permeability and retention (EPR) to macromolecules associated with tumor vasculature. Pharmaceutical shortcomings of certain active camptothecins including difficulty in formulation and instability of the active lactone form due to interactions with human albumin might be improved by conjugation to polymers. In this report, conjugations of camptothecin (CPT), 10-hydroxy-CPT, and 9-amino-CPT to poly-(L-glutamic acid) (PG) are described; coupling was accomplished either through the 20(S)-hydroxyl or 9 and 10 substituents with and without the use of a glycine linker. Studies using a PG paclitaxel conjugate (PG TXL), which is currently in Phase I testing, demonstrated that PG enhanced aqueous solubility, prolonged plasma residence time, and greatly increased the distribution of paclitaxel to tumor tissue in a murine model. In this report, we describe the use of similar conjugation technology for CPT derivatives and demonstrate that these difficult to formulate compounds can be rendered water soluble, that their maximum tolerated doses are increased, and that they retain substantial anti-tumor activity in syngeneic and xenogeneic tumor models. Preliminary data suggest that PG with molecular weights between 37 and 50 kDa with CPT loading between 14% and 37% with or without glycine linkers display enhanced efficacy compared with nonconjugated camptothecins administered at their maximum tolerated dose. PMID- 11193890 TI - 9-Nitrocamptothecin liposome aerosol treatment of human cancer subcutaneous xenografts and pulmonary cancer metastases in mice. AB - The purpose of this study was to test the anticancer properties of the water insoluble derivative of camptothecin, 9-nitrocamptothecin (9NC), administered in a liposome formulation (L-9NC) in aerosol to mice with subcutaneous xenografts of three human cancers and in mice with murine melanoma and human osteosarcoma pulmonary metastases. The drug was formulated with dilauroylphosphatidylcholine and nebulized in particle sizes of 1.2-1.6 microns mass median aerodynamic diameter and a geometric standard deviation of 2.0. The aerosol was generated with the nebulizer flowing at 10 l/min and delivered to mice in sealed plastic cages or in a nose-only exposure chamber. Aerosol was administered for 15 min to 2 hr daily, delivering deposited doses in the respiratory tract of 8.1-306.7 micrograms of 9NC/kg. With subcutaneous tumors, growth was greatly inhibited or tumors were undetectable after several weeks of treatment. We also showed that oral dosage with L-9NC had no detectable effect on cancer growth, and thus the benefit from aerosol treatment was due to pulmonary deposition and not the larger fraction of drug deposited in the nose of mice during aerosol treatment which is promptly swallowed. Intramuscular L-9NC in slightly larger doses than given in the aerosol had detectable anticancer activity, but it was significantly less than in mice receiving the drug by aerosol. With metastatic pulmonary cancers, treated animals showed highly significantly less cancer growth than control animals. L-9NC aerosol showed a major therapeutic benefit in the treatment of subcutaneous human cancer xenografts in nude mice, suggesting that cancers at systemic sites might be responsive to this treatment. In addition, the strong anticancer effect of L-9NC aerosol on pulmonary metastases offers a therapeutic approach for treatment of pulmonary cancers. Thus, L-9NC aerosol may have applicability in the treatment of cancers throughout the body. PMID- 11193891 TI - Modified lactone/carboxylate salt equilibria in vivo by liposomal delivery of 9 nitro-camptothecin. AB - The lactone stability of camptothecins is critical for their anticancer activity. A stable liposomal 9-nitro-camptothecin formulation was developed to circumvent the drawbacks of low aqueous solubility and lactone instability and to provide sustained release of the agent in blood circulation. The potential merits of the formulation were demonstrated by its profoundly improved lactone stability in vivo, favorable pharmacokinetic and biodistribution characteristics in rats, and enhanced preclinical efficacy in tumor-bearing athymic mice. PMID- 11193892 TI - New analogues of camptothecins. Activity and resistance. PMID- 11193893 TI - Intraperitoneal topoisomerase-I inhibitors. Preliminary findings with 9 aminocamptothecin. AB - The i.p. administration of topoisomerase I (Topo I) inhibitors has a pharmacologic advantage over intravenous application, including preservation of the biologically active lactone form. In our ongoing study, patients have received 9-amino-20(S)-camptothecin (9-AC) i.p. on days 1, 3, 5, 8, 10, and 12, repeated every 4 weeks. The daily dose has been escalated to level IV of 1.5 mg/m2 (9.0 mg/m2 per course), median of 3 cycles, range 1-4, with a reversible Grade 3 neutropenia in one patient. Responses included one CR (resolution of a pleural effusion), two patients without progressive disease (PD), two not evaluable, and two patients too early for evaluation. The area under the curve (AUC)i.p./AUCpl ratio (pharmacologic advantage) ranged from 7.6 to 16.5 on average, and, using nonlinear modeling, the pharmacologic decay data were fit to one- or two-compartmental models. Overall, a 9-AC i.p. application is well tolerated and anticipated to be an active regimen against i.p. malignancies, particularly those known to be sensitive to systemic Topo-I inhibitors. PMID- 11193894 TI - Transport of topoisomerase I inhibitors by the breast cancer resistance protein. Potential clinical implications. AB - The multidrug resistance protein BCRP (breast cancer resistance protein) is a member of the ATP-binding cassette family of drug transporters. Overexpression of BCRP caused by exposure of cells to mitoxantrone (MX) or doxorubicin/verapamil resulted in a resistance pattern that is different from what is generally seen in the case of P-glycoprotein and MRP1 overexpression. Recently, the BCRP gene has been described in ovarian, breast, colon, and gastric cancer and fibrosarcoma cell lines. Our human tumor cells T8 and MX3, derived from the ovarian cancer cell line IGROV1 by stepwise increased exposure to topotecan and MX, are resistant to topotecan, CPT11, SN38, and 9-aminocamptothecin as well as MX. Increased energy-dependent efflux of affected drugs was noted. BCRP is a very efficient transporter of topotecan. Our recent studies, using the monoclonal antibody (mAb) BXP34, revealed that BCRP is located in the plasma membrane of the T8 and MX3 cell lines. Preliminary results of staining of human tumor cells showed low or absent levels of BCRP in a panel of solid tumors and acute myeloid leukemia cells. PMID- 11193895 TI - Pharmacokinetics of orally administered camptothecins. AB - Phase I trials of oral camptothecins, including camptothecin (CPT) and irinotecan (CPT-11), have reported substantial interpatient variability in systemic exposure, which could result in suboptimal antitumor activity in some patients or enhanced risk for toxicity in others. This investigation evaluates the contribution of intestinal absorption and first-pass metabolism in the disposition of oral CPT and CPT-11, respectively. The transport of CPT in Caco-2 cell lines (validated model of intestinal drug transport) was concentration dependent and saturable (Vmax: 34 x 10(-5) cm/sec and Km: 20 microM), and was temperature dependent with an activation energy (Ea) of 11.7 kcal/mole. Cumulatively, this data was indicative of carrier-mediated intestinal transport. In addition, a reduction of transport in the presence of sodium azide plus deoxyglucose suggested ATP dependence. Thus, variable expression and availability of intestinal transporters could contribute to the observed wide variability in the exposure to oral CPT. CPT-11 is hydrolyzed by the ubiquitous enzyme carboxyl esterase to active SN-38, and first-pass metabolism of oral CPT-11 would include both intestinal and hepatic hydrolysis. Incubation of CPT-11 with S9 fractions of human liver and intestinal tissues resulted in variable rates of formation of SN 38. The mean (+/- SD) specific activities (pmoles/min/mg) were: liver (8.57 +/- 10.4, n = 8), duodenum (5.06 +/- 3.7, n = 4), jejunum (6.44 +/- 2.8, n = 5), ileum (4.81 +/- 2.4, n = 5), colon (1.93 +/- 1.5, n = 6), and rectum (0.82, n = 1). Interestingly, there was a decrease in SN-38 formation by tumor tissue compared to matched normal liver and colon tissues. Therefore variable first-pass metabolism could contribute to the substantial differences in the systemic exposures to CPT-11 and SN-38 in patients receiving oral CPT-11. PMID- 11193896 TI - Metabolism of CPT-11. Impact on activity. AB - Irinotecan (CPT-11) is a semi-synthetic camptothecin with a broad spectrum of clinical activity. It is a prodrug that is cleaved by esterases to the potent topoisomerase I poison, SN-38. In humans, this activation is relatively inefficient, but this may result in a more protracted formation of SN-38 lactone. Some intratumoral activation may also occur, but the significance of this process is uncertain. CPT-11 is metabolized by cytochrome P450 3A to yield a number of comparatively inactive compounds. SN-38 is glucurono-conjugated in the liver, and this metabolite, although inactive, may participate in the enterohepatic cycling of SN-38 after hydrolysis in the intestinal lumen. Overall, the production of SN 38 from CPT-11 is the result of the complex interplay of several metabolic pathways and the source of considerable interpatient variability. PMID- 11193897 TI - Pharmacology of camptothecin esters. AB - An intact lactone ring of camptothecins is a structural requirement for their anticancer activity. Propionate esters of camptothecin (CPT) and 9 nitrocamptothecin (9NC), CZ48 and CZ112, respectively, have been synthesized as derivatives resistant to lactone hydrolysis and are chemotherapeutically active. In this study, we have examined the mechanism of action of CZ48 and CZ112 and their distribution, metabolism, and toxicity. CZ112 incubated in human plasma retained its lactone structure longer than 9NC (t1/2: 10.5 and < 1 hr for CZ112 and 9NC, respectively). This resistance to lactone hydrolysis was also observed in mouse plasma or albumin solutions. Neither CZ48 nor CZ112 inhibit topoisomerase I and thus are prodrugs dependent on hydrolysis to CPT or 9NC, respectively. Rates of hydrolysis of CZ48 to CPT are higher by homogenates of mouse liver, spleen, lung, and kidney than by plasma. Rates of hydrolysis by tumor cells in culture vary and were higher by breast cancer and melanoma cells than by colon cancer cells. On the basis of these and other data, it is proposed that CZ48 and CZ112 may act as anticancer agents by resisting hydrolysis to camptothecins while in circulation. Hydrolysis in tissues may release intact lactone in target tissues. PMID- 11193898 TI - The clinical development of 9-aminocamptothecin. AB - 9-Aminocamptothecin (9-AC) is a topoisomerase I-targeting agent first synthesized by Wani and Wall in 1986. Because of its potent in vitro effects and promising preclinical activity in colorectal cancer animal models, it was designated a high priority compound for further drug development by the NCI. In 1993, 9-AC first entered clinical trials as a 72-hour intravenous (i.v.) infusion. Predictable myelosuppression was the major dose-limiting toxicity, and pharmacokinetic studies showed a relatively short plasma half-life and unstable lactone ring. Unfortunately, phase II studies using this schedule showed minimal or no activity in tumors such as colorectal and lung cancer. Modest activity was observed in ovarian cancer and in refractory lymphomas. Efforts to improve systemic drug exposure by utilizing alternative schedules of administration of 9-AC such as prolonged, continuous intravenous infusions have also been tested. However, phase II studies of 120-hour weekly infusions of 9-AC have not shown improved activity against solid tumors such as colorectal cancer. More recently, a daily times 5 days i.v. administration schedule has been tested. Currently, further development of intravenously administered 9-AC for the treatment of colorectal cancer is not promising. Thus, topotecan and irinotecan remain the only two successfully developed topoisomerase I-targeting drugs in the United States. This experience with 9-AC raises important questions regarding how to best select new topoisomerase I-targeting drugs for future clinical development. PMID- 11193899 TI - Alternative administration of camptothecin analogues. AB - The binding of camptothecin (CPT) to the DNA-topoisomerase complex is reversible, but it needs to be maintained for maximal inhibitory activity. It is also dependent on the chemical structure of CPT. The lactone form is thought to be necessary for the activity. In human serum, the equilibrium between lactone and carboxylate is in favor of the latter. For these reasons, alternative administration of CPT analogues is being evaluated. The ideal compound would remain in lactone form and would expose the host for long periods of time to its effects. Oral administration of irinotecan (CPT-11) and topotecan (TPT) is discussed by other investigators. We studied oral rubitecan and reported a low lactone to total drug area under the plasma concentration-time curve (AUCP) ratio (14.7%), with low plasma concentration over time despite repeated administrations and the presence of an enterohepatic cycle. Aerosolization of a liposomal formulation of rubitecan is currently under study. Six patients have been treated once a day for 5 days every 3 weeks. The dose was 6.7 micrograms/kg/day. Plasma levels are dose for dose higher than those after oral administration, but the ratio of lactone versus total drug is low. No toxicity was observed. The study will continue with increasing doses and lengths of administration. Intrathecal administration of topotecan has been studied in a phase I trial in children. Doses of 0.4 mg are tolerated without toxicity, and clinical responses have been seen in patients with refractory meningial carcinomatosis. Phase II studies are planned. Intraperitoneal (i.p.) administration of topotecan has been studied in a phase I trial as a 24-hour infusion in 5% dextrose at pH 3.5 every 21 days. Dose limiting toxicity is 4 mg/m2. Toxic effects are neutropenia, anemia, emesis, fever, and pain. Five of 10 patients with ascites had symptomatic relief. Pharmacokinetic analysis demonstrates a second-order kinetics with elimination half-lives of 0.49 and 2.7 hours. The peritoneal to plasma AUC ratio was 31.2. Intramuscular, transdermal, and subcutaneous administrations have been extensively studied in the mouse. PMID- 11193900 TI - Topotecan (hycamptin) and topotecan-containing regimens in the treatment of hematologic malignancies. AB - Single-agent topotecan is an active drug in chemotherapy-naive MDS and CMML and, to a lesser degree, in refractory/relapsed acute leukemias, low-/intermediate grade lymphoma, and myeloma. Its combination with cytosine arabinoside induces complete remissions in high-risk MDS/CMML. A triple-combination regimen of cyclophosphamide, cytosine arabinoside, and topotecan (CAT) was extensively tested in refractory/relapsed as well as in untreated AML. By proving effective in inducing complete remission in newly diagnosed AML at rates comparable to those achieved by anthracycline-cytosine arabinoside regimens, for example, CAT offers a useful treatment alternative. Topotecan combined with paclitaxel is promising in low-/intermediate-grade lymphomas. The activity of topotecan justifies further evaluation of topotecan-containing combination regimens, particularly in MDS/CMML and acute leukemias. PMID- 11193901 TI - DX-8951f: summary of phase I clinical trials. AB - Exatecan mesylate (DX-8951f) is a new hexacyclic camptothecin analogue with favorable attributes compared to topotecan and CPT-11, including watersolubility, greater potency against topoisomerase I, lack of esterase-dependent activation, broad antitumor activity, and low cross-resistance against MDR-1 overexpressing tumors. In preclinical studies, the compound demonstrated a favorable toxicology profile with hematologic dose-limiting toxicity and moderate gastrointestinal toxicity, linear pharmacokinetics, P450 hepatic metabolism (CYP3A4 and CYP1A2), and predominately fecal excretion. The results of six U.S. and European phase I clinical trials as well as two Japanese studies are presented including total DX 8951 and lactone DX-8951 pharmacokinetics. The toxicity profile was similar for all schedules of administration. Hematologic toxicity was dose-dependent and reversible. Neutropenia was dose-limiting in minimally pretreated patients, whereas neutropenia and thrombocytopenia were dose-limiting in heavily pretreated patients. Non-hematologic toxicity included moderate gastrointestinal toxicity (nausea, vomiting > diarrhea), transient elevation of hepatic transaminases, asthenia, and alopecia. Two cases of acute pancreatitis not predicted by preclinical toxicology were also observed. Antineoplastic activity was detected in several solid tumor types: non-small cell lung cancer, extrapulmonary small cell cancer, colorectal cancer, hepatocellular cancer, and sarcoma. Antitumor activity was seen in CPT-11 and topotecan-resistant tumors. Pharmacokinetics were linear within the dose range tested. A pharmacokinetic/pharmacodynamic model predictive of DX-8951f-induced neutropenia in individual patients was developed. The daily x5, every 3-week schedule with the drug administered as a 30-minute intravenous infusion was selected for future phase II clinical trials based on its superior antitumor activity. PMID- 11193902 TI - Dependence of anticancer activity of camptothecins on maintaining their lactone function. AB - Camptothecins contain a lactone ring that exists in the closed form below ph 7. Above 7, the open (CPT+) and the closed (CPT) form coexist in a 50-50 ratio in mouse plasma and in a 90-10 ratio in human plasma due to the high affinity of human serum albumin (HSA) for CPT+. CPT+ is much less toxic than CPT and it is excreted much faster. In complete RPMI 1640 culture medium, the equilibrium CPT(+)-CPT is 50-50. If 4% HSA is added, it moves to 90-10 modeling for the human physiological situation. PMID- 11193903 TI - Cellular and molecular responses to topoisomerase I poisons. Exploiting synergy for improved radiotherapy. AB - The efficacy of topoisomerase (Topo) I-active drugs may be improved by better understanding the molecular and cellular responses of tumor compared to normal cells after genotoxic insults. Ionizing radiation (IR) + Topo I-active drugs (e.g., Topotecan) caused synergistic cell killing in various human cancer cells, even in cells from highly radioresistant tumors. Topo I poisons had to be added either during or immediately after IR. Synergy was caused by DNA lesion modification mechanisms as well as by concomitant stimulation of two pathways of cell death: necrosis (IR) + apoptosis (Topo I poisons). Cumulative data favor a mechanism of synergistic cell killing caused by altered DNA lesion modification and enhanced apoptosis. However, alterations in cell cycle regulation may also play a role in the synergy between these two agents in certain human cancers. We recently showed that NF-kappa B, a known anti-apoptotic factor, was activated in various cancer cells after poisoning Topo I using clinically active drugs. NF kappa B activation was dependent on initial nuclear DNA damage followed by cytoplasmic signaling events. Cytoplasmic signaling leading to NF-kappa B activation after Topo I poisons was diminished in cytoplasts (lacking nuclei) and in CEM/C2 cells that expressed a mutant Topo I protein that did not interact with Topo I-active drugs. NF-kappa B activation was intensified in S-phase and blocked by aphidicolin, suggesting that activation was a result of double-strand break formation due to Topo I poisoning and DNA replication. Dominant-negative I kappa B expression augmented Topo I poison-mediated apoptosis. Elucidation of molecular signal transduction pathways after Topo I drug-IR combinations may lead to improved radiotherapy by blocking anti-apoptotic NF-kappa B responses. Recent data also indicate that synergy caused by IR + Topo I poisons is different from radiosensitization by beta-lapachone (beta-lap), a "reported" Topo I and II-alpha poison in vitro. In fact, beta-lap does not kill cells by poisoning either Topo I or II-alpha in vivo. Instead, the compound is "activated" by an IR (damage) inducible enzyme, NAD(P)H:quinone oxidoreductase (NQO1), a gene cloned as x-ray inducible transcript #3, xip3. Unlike the lesion modification pathway induced by IR + Topo I drugs, beta-lap kills cells via NQO1 futile cycle metabolism. Downstream apoptosis caused by beta-lap appears to be noncaspase-mediated, involving calpain or a calpain-like protease. Thus, although Topo I poisons or beta-lap in combination with IR both synergistically kill cancer cells, the mechanisms are very different. PMID- 11193904 TI - In vitro antitumor activity of 9-nitro-camptothecin as a single agent and in combination with other antitumor drugs. AB - Preclinical studies at Roswell Park Cancer Institute by Minderman, Cao, and Rustum (unpublished results) showed that a combination of SN-38 and 5-FU against HCT-8 human colon carcinoma cells in vitro was synergistic, with the best interaction occurring when the drugs were added sequentially, SN-38 first. Their in vivo studies using HCT-8 tumor xenografts implanted s.c. in nude athymic mice demonstrated superior efficacy for a sequential i.v. administration of CPT-11, 24 hr before 5-FU. On the basis of these studies, our group has begun to evaluate effects of RFS2000 (9-nitro-20(S)-camptothecin) (9-NC) in combination with a series of other antitumor agents. Using a panel of human tumor cell lines including A121 ovarian cancer, HCT-8 colon cancer, H-460 NSCLC, HT-1080 fibrosarcoma, and MCF7 mammary cancer, we found that a 2-hr exposure to 9-NC resulted in ID50 values of < 1.0 microM, whereas continuous exposure to drug resulted in ID50 values of < 1.0 nM. Tumor growth inhibitory activities of 5-FU, gemcitabine, and paclitaxel were determined for comparison. Combinations of these agents were evaluated with 9-NC using the human HCT-8 colon tumor cell line. Concurrent and sequential combinations of 9-NC with 5-FU had some regions of the concentration-effect surface with local synergy and some with local antagonism. However, sequential combination of 9NC or SN-38 followed by 5-FU, 24 hr later appeared to be highly synergistic at high dose-effect levels (i.e., ID90), suggesting that sequential drug administration may be more efficacious at high effect level and that the order of drug addition is very important. Overall, our results were similar to that found earlier by Rustum's group with CPT11 (or SN 38) and 5-FU, suggesting that sequential combination of 9-NC (or other camptothecin analogues) followed by 5-FU has potential for the treatment of cancer in man. PMID- 11193905 TI - p53 and p21 are major cellular determinants for DNA topoisomerase I-mediated radiation sensitization in mammalian cells. PMID- 11193906 TI - The homocamptothecin, BN 80927, is a potent topoisomerase I poison and topoisomerase II catalytic inhibitor. PMID- 11193907 TI - The dual topoisomerase inhibitor, BN 80927, is highly potent against cell proliferation and tumor growth. PMID- 11193908 TI - Ubiquitin, SUMO-1, and UCRP in camptothecin sensitivity and resistance. PMID- 11193909 TI - A spectrophotometric study of the pH-dependent and DNA binding properties of topotecan. PMID- 11193910 TI - Kinetics of in vitro hydrolysis of homocamptothecins as measured by fluorescence. PMID- 11193911 TI - The combinatorial synthesis of racemic homosilatecan libraries via a cascade radical annulation. PMID- 11193912 TI - Combined radiation and 9-nitrocamptothecin (rubitecan) in the treatment of locally advanced pancreatic cancer. PMID- 11193913 TI - Preclinical and phase I clinical studies with Ckd-602, a novel camptothecin derivative. PMID- 11193914 TI - Action of topoisomerase targeting drugs on non-Hodgkin's lymphoma and leukemia. Correlation of clinical and cell culture studies. PMID- 11193915 TI - Improvement of therapeutic index of low-dose topotecan delivered per os. PMID- 11193916 TI - Camptothecin dose, schedule, and timing of administration for clinical radiation sensitization. PMID- 11193917 TI - Rapid chromatin reorganization induced by topoisomerase I-mediated DNA damage. PMID- 11193918 TI - NF-kappa B activation in topoisomerase I inhibitor-induced apoptotic cell death in human non-small cell lung cancer. PMID- 11193919 TI - Phase I study of 9-nitro-20(S)-camptothecin in combination with cisplatin for patients with advanced malignancies. PMID- 11193920 TI - Phase II study of intravenous DX-8951f in patients with advanced ovarian, tubal, or peritoneal cancer refractory to platinum, taxane, and topotecan. PMID- 11193921 TI - Feasibility, phase I, and pharmacological study of aerosolized liposomal 9-nitro 20(S)-camptothecin in patients with advanced malignancies in the lungs. PMID- 11193922 TI - Inhibition of DNA replication in camptothecin-treated cells is regulated by protein kinases. PMID- 11193923 TI - Camptothecin design and delivery approaches for elevating anti-topoisomerase I activities in vivo. AB - The camptothecins as a class have exhibited unique dynamics and reactivity in vivo, with respect to both drug hydrolysis and blood protein interactions. These factors have confounded their pharmaceutical development and clinical implementation. Recent bench and clinical research alike indicates that the combination of medicinal chemical and drug delivery approaches has been and will continue to be highly valuable in improving the overall therapeutic indices of camptothecin-based anti-topoisomerase I therapies. In the future the development of camptothecin analogues that exhibit highly specific human albumin interactions will likely be avoided, and agents such as the highly lipophilic DB-67 analogue with improved tissue stability will be evaluated. Drug delivery scientists will also devise better ways of targeting camptothecin therapies to solid tumors by using carriers such as tumor-targeted long-circulating liposomes. PMID- 11193924 TI - Mechanisms of resistance to camptothecins. AB - Camptothecins are broad-spectrum anticancer drugs that specifically target DNA topoisomerase I. Although the availability of camptothecins has had a significant impact on cancer therapeutics, de novo or acquired clinical resistance to camptothecins is common. Studies of camptothecin resistance using yeast and mammalian cell culture models suggest three general mechanisms of resistance: (1) reduced cellular accumulation of camptothecins, (2) alteration in the structure or location of topoisomerase I, and (3) alterations in the cellular response to camptothecin-DNA-ternary complex formation. The relevance of these mechanisms to clinical drug resistance is not yet known, but evaluation of these models in clinical specimens should enhance the use of camptothecins both as single agents and in combination with other anticancer drugs. PMID- 11193925 TI - Structure-based analysis of the effects of camptothecin on the activities of human topoisomerase I. AB - The sole target for the anticancer drug camptothecin (CPT) is the type I topoisomerase. The drug poisons the topoisomerase by slowing the religation step of the reaction, thereby trapping the enzyme in a covalent complex on the DNA. In addition, CPT has been shown to inhibit plasmid DNA relaxation in vitro. The structural bases for these two activities of CPT are explored in relation to the recently published crystal structure of the enzyme with bound DNA. PMID- 11193926 TI - Mechanisms of DNA topoisomerase I-induced cell killing in the yeast Saccharomyces cerevisiae. AB - DNA topoisomerase I (Top1) catalyzes the relaxation of supercoiled DNA by a mechanism of transient DNA strand cleavage characterized by the formation of a phosphotyrosyl bond between the DNA end and active site tyrosine. Camptothecin reversibly stabilizes the covalent enzyme-DNA intermediate by inhibiting DNA religation. During S-phase, collisions with advancing replication forks convert these complexes into potentially lethal lesions. To define the DNA damage induced by alterations in Top1p catalysis and the cellular processes that mediate the repair of such lesions, the yeast Saccharomyces cerevisiae was used. Substitution of conserved residues N-terminal to the active site tyrosine (Tyr-727) produced alterations in the camptothecin sensitivity or catalytic cycle of DNA Top1. For example, substituting Ala for Thr-722 in Top1T722A increased the stability of the covalent enzyme DNA intermediate. As with camptothecin, Top1T722A-induced cytotoxicity was ascribed to a reduction in DNA religation. By contrast, enhanced covalent complex formation by Top1N726H resulted from a relative increase in the rate of DNA cleavage. Conditional yeast mutants were also selected that exhibit temperature-sensitive growth only in the presence of the self-poisoning Top1T722A enzyme. Subsequent analyses of these tah mutants identified 9 genes whose function suppresses the cytotoxic action of camptothecin and Top1T722A. These include genes encoding essential DNA replication proteins (CDC45 and DPB11) and proteins involved in SUMO- or ubiquitination (UBC9 and DOA4). PMID- 11193927 TI - Camptothecins as probes of the microenvironments of topoisomerase I--DNA complexes. AB - By uncoupling the cleavage and ligation reactions of DNA oligonucleotides mediated by topoisomerase I, it has been possible to demonstrate modification of DNA oligonucleotide structure by the enzyme. These modifications indicate an unusual flexibility inherent in the behavior of topoisomerase I and may reflect some of the cellular roles played by the enzyme. The ability of individual camptothecin analogues to inhibit these modification processes differentially provides insight into the relative nature of the microenvironments present. To the extent that these enzyme-mediated structural modifications do constitute models of cellular roles for the enzyme, the observed differential inhibition also provides a potential strategy for assessing the function and importance of such modifications. PMID- 11193928 TI - Preclinical and clinical trials of topoisomerase inhibitors. AB - CPT-11, developed by Yakult Honsha, has achieved the position of standard chemotherapy for colorectal cancer in the United States and in Western countries because CPT-11 + 5FU + LV showed survival benefit compared with 5FU-LV in two randomized controlled trials. CPT-11 has been distributed to almost all countries. In Japan, combination therapy of CDDP + CPT-11 was significantly superior to CDDP-VP-16 in the treatment of extensive disease small cell lung cancer. This combination is also active against non-small cell lung cancer. Daiich Pharmaceutical Co. developed a more active nonmasked form of camptothecin derivative, DX-8915f. The phase I study of a new camptothecin inhibitor, DX 8915f, has just been completed. The new topoisomerase I inhibitors of indolocarbazol derivatives, NB-506 and J107088, developed by Banyu Co., have strong antitumor activity and a wide therapeutic ratio. The phase I trial of J107088 is currently ongoing in the United States and Japan. These do not show any cross-resistance to MDR drugs. PMID- 11193929 TI - The Camptothecins: Unfolding Their Anticancer Potential. Proceedings of a conference. March 17-20, 2000, Arlington, Virginia, USA. PMID- 11193930 TI - [Establishment and characterization of rat myelomonocytic leukemia clones undergoing differentiation or apoptosis]. AB - It has not clearly been elucidated how differently differentiation-inducing drugs act on tumor cells, whether they promote differentiation or apoptosis. To elucidate the mechanisms whether leukemic cells responding to ONO-4007, a lipid A derivative, undergo differentiation or apoptosis, we established two cell clones from a rat myelomonocytic leukemia c-WRT-7/P2 clone which undergoes differentiation followed by apoptosis by ONO-4007-treatment. One of the clones (1D6) showed the features of differentiation, such as phagocytosis when treated with ONO-4007 more than 24 hrs. The other clone (3B1) clearly showed the features of apoptosis, such as DNA ladder formation within 24 hrs after incubation with ONO-4007. We then examined expression of CD14, p21, p38MAPK, JNK/SAPK, and bcl-2, functional p53 statuses and cell cycle in these two clones, and revealed the following: Without treatment with ONO-4007; 1) CD14, p21, and bcl-2 proteins were equally expressed in both clones; 2) wild-type and non-functional mutated-type p53 were present in both clones and the p53 in 3B1 clone was recessive whereas that in 1D6 clone was dominant negative; 3) p38MAPK in 3B1 clone was already phospholyrated whereas that in 1D6 clone was not. After treatment with ONO-4007; 1) neither expressions of CD14 nor that of p21 protein was changed in any of the clones; 2) p38MAPK in 3B1 clone was dephospholyrated at 1 and 2 hrs after treatment whereas that in 1D6 clone was phospholyrated at 4 and 8 hrs after treatment; 3) the expression of bcl-2 protein in 3B1 clone was reduced. These findings suggest that p53 may be one of the key factors in leading these cells to differentiation or apoptosis, and that bcl-2 may suppress the apoptosis. PMID- 11193931 TI - [Development of a detection system (APC yeast color assay) of APC mutations by color change of yeast]. AB - The author developed a sensitive yeast-based color assay which expresses APC-ADE2 (reporter) fusion protein in yeast and can screen almost the entire coding region of the APC gene. In this assay, the wild-type APC coding sequence of 8.5 kb is divided into 5 overlapping regions which are respectively ligated in-frame with an ADE2 open reading frame. The resulting five constructs containing a part of wild-type APC gene preserve the ADE2(+) phenotype (white yeast colony) when introduced into the yeast, whereas the yeast transfected with plasmids containing frameshift mutations of the APC gene shows an ADE2(-) phenotype (red yeast colony). Six human colon cancer cell lines were analyzed by this yeast color assay. HCT116 cells with wild-type APC and normal colonic mucosa gave low percentages of red colonies (0-9.9%) in all the regions. On the other hand, more than 96% red colonies were observed in one of the five regions in SW480, Colo201 and Colo320DM cells. Sequence analysis demonstrated the clonal APC mutations at codon 1,338 in SW480, 1,554 in Colo201 and 811 in Colo320DM. Moreover, the assay detected a germline mutation of the APC gene in polyps of a familial adenomatous polyposis (FAP) patient which gave about 50% red colonies. For testing the assay for clinical utilization, 18 colon cancer tissues were subjected to the assay. Eleven cancers (61%) gave more than 10% red colonies (17-57%) and clonal mutations were detected in all these samples. The same mutations were demonstrated in both DNA and RNA samples derived from idendical tissues. These results suggest that this APC yeast color assay is powerful means for detection of APC mutations in clinical samples. PMID- 11193932 TI - [Roles of neuropeptide Y in the expression of anticipatory corticosterone peak in rats under restricted daily feeding]. AB - NPYmRNA in the arcuate nucleus (ARC) and the nucleus of the solitary tract (NST) was measured by quantitative RT-PCR and in situ hybridization in rats under 48 hour food deprivation (FD) or under restricted daily feeding (RF) in which free access to food was restricted to 2 hours per day for 3 weeks. Plasma corticosterone levels were elevated immediately prior to daily food supply under RF, while they remained essentially unchanged by 48-hour FD. On the other hand, the NPYmRNA levels in the ARC were increased by 48-hour FD and RF, while those in the NST were elevated by RF but not by 48-hour FD. These findings indicate that the NPY neurons in the NST are specifically involved in the prefeeding corticosterone peak in the rats the under RF, while the NPY neurons in the ARC are involved in the feeding activity in general and stimulated by decreased food availability. PMID- 11193933 TI - [Development of a new method for sequential monitoring of transcriptional activities of growth hormone genes by a secreted bioluminescence reporter]. AB - The genetic reporter system has been introduced as a tool for sensitive and convenient monitoring of gene expression. In the present study, the promoter activity of growth hormone (GH)-coding gene was sequentially monitored in GH3 cells (rat pituitary adenoma cell-line) by means of bioluminescence which was evoked by a secreted reporter, Vargula hilgendorfii (VH) luciferase. Three kinds of expression plasmids were constructed, which consisted of a rat GH promoter fragment and VH luciferase cDNA, and transfected into GH3 cells. The sensitivity of the reporter was revealed to be extremely high from the dose-response curve of VH luciferase. With the use of the stable transformant, the reporter activity as well as that of GH was sequentially measured in plate culture. The intracellular dynamics of reporter signals was analyzed through the response to inhibitors of transcription, protein synthesis and vesicle transport, which suggested that the overall time from transcription to secretion was essentially identical to those of the VH luciferase and GH although the both proteins took different time course at different intracellular stages. When the GH promoter was activated by triiodothyronine (T3), the reporter activity was enhanced, and well correlating with the amount of GH mRNA, which indicated a reliability of the reporter system. Furthermore, in the present reporter system, a synergistic effect of T3 and dexamethasone was observed not only on the GH transcription but also on the stability of mRNA. It is concluded that the bioluminescence reporter system using the VH luciferase is an excellent tool for sequential monitoring of the GH transcriptional activity. PMID- 11193934 TI - [Anxiolytic effects of serotonin reuptake inhibitors and their mechanism of action]. AB - The purpose of this study was to examine the anxiolytic effects of serotonin (5 HT) reuptake inhibitors and to clarify their action mechanisms and roles in the brain serotonergic system in the psychopathology of anxiety. It has been proposed that conditioned fear stress (CFS)-induced freezing behavior in rats could be used as a model of anxiety. In the experiment using this model, acute treatment with the 5-HT reuptake inhibitors reduced CFS-induced freezing behavior, while acute treatment with the noradrenaline or dopamine reuptake inhibitors failed to alter CFS-induced freezing. CFS elevated extracellular 5-HT levels in the medial prefrontal cortex, and this elevations of 5-HT level was followed by a resolution of the freezing. A dose of 10 mg/kg of a selective 5-HT reuptake inhibitor (SSRI), citalopram, administered 60 min before exposure to CFS increased extracellular 5-HT concentrations immediately and potently, and reduced freezing. The 5-HT1A receptor antagonists, particularly at low doses, enhanced the antifreezing effect of citalopram. While the antifreezing effect of citalopram (10 mg/kg) disappeared by prolongation of the period between conditioning and exposure to CFS, acute challenge of citalopram (10 mg/kg) reduced freezing in the rats into which citalopram (10 mg/kg) had been injected twice daily for 7 days. From these findings, it is indicated that 1) 5-HT reuptake inhibitors decrease anxiety, 2) 5-HT release is increased at the nerve terminal under anxiety conditions, 3) the elevation of 5-HT levels in the terminal has an anxiolytic action which is closely related to the pharmacological effects of SSRI-class of anxiolytics, and 4) 5-HT1A receptor antagonist enhances the antifreezing effect of SSRI by blocking the autoreceptor-mediated negative feedback mechanisms of 5 HT neurons. By prolonging the period between conditioning and exposure to CFS, the author recognized the feasibility to establish an animal model which reflects the psychopathology of anxiety disorder more precisely. Presynaptic 5-HT1A receptor desensitization may account for the mechanism of action of repeated treatment with SSRI. PMID- 11193935 TI - The main factor causing prolonged reaction time on force producing process following anterior cruciate ligament reconstruction. AB - This study investigated the electromechanical properties of atrophied human quadriceps femoris muscle during a voluntarily elicited maximal isometric contraction (MVC) and a peripherally stimulated twitch contraction. Nineteen patients were recruited 2-3 months following a unilateral anterior cruciate ligament (ACL) reconstruction. Both the involved leg as well as the uninvolved leg were studied. Maximal twitch response was elicited and surface electromyograms (EMG) were recorded from the vastus lateralis. Total reaction time (TRT) for both MVC and twitch on involved leg was prolonged (251.47 msec, 26.01 msec). This prolongation suggests an extended lag in avoiding injury such as during sports. Pre-motor time during both MVC and twitch (PMTmvc, PMTtwitch) did not differ between both groups. Electromechanical delay during MVC (EMDmvc) was prolonged on involved leg (53.42 msec), and also evoked twitch EMD (EMDtwitch) (20.04 msec) as compared to the opposite side. Prolonged EMDtwitch may be due to a decrease in stiffness of the series elastic component, changes of peripheral muscle composition to containing more slow type muscle fibers, or a decrease in function of the excitation-contraction (E-C) coupling process. A prolonged EMDtwitch can also explain the prolonged EMDmvc. These findings also suggested that prolonged TRTmvc to visual stimulus during MVC in atrophied human quadriceps femoris muscle after disuse was principally due to prolongation of EMDmvc. Prolonged EMDmvc may have resulted from decreased muscle stiffness, which was evident in the prolongation of the EMDtwitch. PMID- 11193936 TI - Bilateral simultaneous oblique MR imaging of the proximal femur. AB - Oblique axial and oblique coronal MR images parallel to the femoral neck provide more valuable information concerning the proximal femur than orthogonal images. The main disadvantage of the unilateral oblique imaging is that the imaging time is significantly increased when both hips need to be imaged. If the bilateral oblique imaging is performed simultaneously, this increase in imaging time is eliminated because the scanning time for the bilateral oblique imaging and the orthogonal imaging is the same. PMID- 11193937 TI - Is communication to endocardium necessary for angiogenesis in transmyocardial laser revascularization? AB - There is evidence of angiogenesis being induced after transmyocardial laser revascularization (TMLR), although the precise mechanism has not been fully elucidated. This study was designed to examine whether or not blood flow from the left ventricle through the channels is essential for angiogenesis following TMLR. Ten dogs underwent the creation of two types of laser channels in the left ventricle: 1) a transmural channel (TMC), which penetrates the myocardium, and 2) a non-transmural channel (NTMC), which does not open to the epicardium. The animals were sacrificed on the 28th postoperative day and the vascular density was examined. Vessels with smooth muscle media were seen within or around the channel remnant. The vessel density was compared between TMC and NTMC. The outer and inner halves of the myocardium in the TMC region were compared in the same way. The density of vessels within and around the channel remnants was significantly higher in TMC than in NTMC (1.439 versus 0.685 vessels/microscopic visual field (mvf=40X); p=0.0025). The vascular density was significantly higher in the region adjacent to TMC than in a distant region (>3 mm from the channel center). The vascular density was significantly higher in the outer half than in the inner half of the myocardium (1.730 versus 1.180 vessels/mvf: p=0.0459). These findings demonstrate that communication to the left ventricular lumen enhances angiogenesis of TMLR, although blood flow in the channel did not exist 4 weeks after TMLR and angiogenesis tended to be more highly enhanced in the outer half than in the inner half of the myocardium. PMID- 11193938 TI - Clinicocytopathological and immunohistochemical study of adenoma malignum of the uterine cervix. AB - Adenoma malignum is a rare type of very highly differentiated adenocarcinoma of the uterine cervix, and is quite difficult to diagnose because there are few findings definitely suggesting malignancy on cytologic or histologic examination. We recently encountered four patients with adenoma malignum and reviewed their clinicocytopathological and immunohistochemical findings. The most characteristic symptom was a watery discharge and an enlarged cervix was palpable, while multiple cystic lesions (MCL) were observed by transvaginal and abdominal ultrasonography, CT or MRI. On cytodiagnosis, the cervical gland cells formed large sheets or showed a palisading arrangement. Slightly enlarged nuclei and yellowish-orange staining of the cytoplasmic mucus were the characteristic findings. On histological examination, many cervical glands of different sizes were present and extended deep into the muscle layer, while branching or papillary growth into the lumen was also observed. On immunohistochemical study, HIK1083, a monoclonal antibody for gastric gland mucous cell mucin, was found to be positive in 3 of 4 cases, and this was fairly useful in the diagnosis of adenoma malignum. PMID- 11193939 TI - Laparoscopic cholecystectomy in a patient on continuous ambulatory peritoneal dialysis. AB - The patient was a 72-year-old man who was receiving continuous ambulatory peritoneal dialysis (CAPD) with a diagnosis of chronic renal failure. Although his response to dialysis therapy was favorable, right hypochondralgia and fever occurred, and gallstones were detected by abdominal ultrasonography and computed tomography. Drip-infusion cholangiography (DIC) revealed neither dilation nor calculus in the common bile duct. The patient was diagnosed as having acute cholecystitis and cholecystolithiasis and, in consideration of his general condition, laparoscopic cholecystectomy was carried out. Pneumoperitoneum was performed through a CAPD tube, and a 10 mm-trocar was carefully introduced through a supraumbilical incision so as not to injure the CAPD tube. Since intraoperative cholangiography showed a condition similar to preoperative DIC, only cholecystectomy was undertaken. The postoperative course was uneventful, with neither postoperative hemorrhage nor leakage of dialysate from the wound. PMID- 11193940 TI - [Macular disease]. PMID- 11193941 TI - [Optic neuritis--from diagnosis to optic nerve transplantation]. AB - Optic neuritis is a clinical syndrome resulting from inflammation, demyelination, or infection of the optic nerve. Its diagnosis and treatment are complicated. In 1884, Nettleship first reported 28 cases of optic neuritis whose clinical symptoms have been accepted up to the present without any change. On the other hand, the development of diagnostic procedures and steroid therapy have also altered the clinical features of optic neuritis. Among several developed diagnostic procedures, the visually evoked cortical potential (VECP) has become a good tool to prove the impairment of the optic nerve. In 1971, we reported a decrease of threshold intensity required to evoke VECPs in optic neuritis patients whose visual acuity was relatively well preserved. In the same year, Halliday et al. reported that pattern VECP (PVECP) was delayed in 93% of patients with multiple sclerosis (MS) without optic neuritis. Stimulated by this report, a great number of studies appeared to show the usefulness of PVECP in the diagnosis of MS. However, few of these studies gave descriptions of ophthalmic findings. PVECP later become known to be closely related with ophthalmic conditions. In the ophthalmological field, we reported the influence of pupillary size, accommodation power, refractive powers, eccentricity of stimulated retinal area, retinal luminance, contrast, wavelengths, spatial and temporal frequencies, stimulus field etc. On the basis of our results, we developed a television display system in 1975 and applied it clinically. In the present study, we reviewed the medical records of a total of 272 cases of optic neuritis who presented in our clinic between 1978 and 1999. In the diagnostic, therapeutic point of view in relation with the data of other countries, the study was important regarding the racial differences and recent conceptions of optic neuritis. The results showed that there were no racial difference in optic neuritis as had been thought. The development from optic neuritis to multiple sclerosis was not less than in Caucasian patients. Regarding steroid therapy, we found that the most effective method was sub-Tenon injection. For cases which recur and progress to optic atrophy, optic nerve transplantation will be needed. Therefore, we have been studying the reconstruction of the optic nerve in Wister rats. We experimentally damaged the ganglion cells by causing ischemic retina with ligation of the ophthalmic artery and cutting the optic nerve just behind the eyeball. To prevent the apoptosis of ganglion cells, we injected various neurotrophic factors such as BDNF, GDNF, and HSP 27 into the vitreous. For effective injection of DNA, electropolation was applied and the best condition for avoiding apoptosis was chosen. Further, in Mx-c-fos transgenic mice, we found that regeneration of ganglion cells was inhibited. Based on the rescue study of the ganglion cells, optic nerve transplantation was performed using an artificial graft in which cultured Schwann cells from the ischiatic nerve, BDNF, CNTF, insulin, and forscolin were compound and bridged to the superior colliculus. The results showed a regeneration rate of the optic nerve axon of 15%. This rate was much higher than in other reports. Keratoplasty and intraocular lens implantation had a relatively long history of research before achieving clinical success. We believe that optic nerve transplantation will one day be successful in clinical treatment in the same way. PMID- 11193942 TI - [Gene expression and the eye]. AB - We examined the role of the expression of the various genes in ocular tissues using knockout mice. In this paper, the results are described in three sections: development, physiology, and pathology. Regarding development, the IKK alpha in the development of the ocular surface and maf family genes in the development of the lens were examined. We clearly demonstrated that the deletion of some genes results in disorganization in the development according to the function of the genes. Regarding physiology, c-fos gene was expressed in the subpopulation of retinal neurons under a physiological light/dark cycle, and its expression is dependent on signal transduction system in the retinal cells. Regarding pathology, focal retinal injury of the retina induced the expression of c-fos mRNA in retinal Muller cells. There is a significant contribution of Jun N terminal phosphorylation to the induction of apoptosis of retinal ganglion cells after optic nerve transection. GLAST is required for normal signal transmission between photoreceptors and bipolar cells and both GLAST and GLT-1 play a neuroprotective role during ischemia in the retina. Blockage of the neurotrophin receptor p 75 rescue photoreceptor apoptosis induced by light exposure whereas the blockage of TrkC increased the photoreceptor cell death. PMID- 11193943 TI - [Treatment of exudative age-related macular degeneration]. AB - I PROPHYLACTIC TREATMENT: We followed 75 eyes contralateral to eyes with exudative age-related macular degeneration (AMD), using indocyanine green angiography (IA), for more than one year. Hyperfluorescent areas in the late phase of IA were seen in 19 eyes at the initial examination, and in 25 eyes during follow-up. Exudative AMD developed in 9 of the 25 eyes. Using timetable analysis, we estimated that 11% of these 27 eyes developed AMD within one year and 55% within three years. The hyperfluorescent areas seen on IA appeared to be latent choroidal neovascularization (CNV) under the retinal pigment epithelium. We propose that photocoagulation aimed at hyperfluorescent areas should be considered in such cases. We performed prophylactic laser photocoagulation in 21 eyes, which were then followed up for at least six months. These eyes all had 10 or more serous drusen within 1,500 microns of the fovea and did not show hyperfluorescence, suggesting latent CNV in the late phase of IA. The majority or a small fraction of the serous drusen disappeared in 48% and 18% of the 21 eyes, respectively. CNV appeared adjacent to the laser scar in one eye (5%). Judging from these results, it is important to establish a method of definitively abolishing drusen and preventing the development of CNV. II TREATMENT OF CNV: Of 229 eyes which showed occult CNV in fluorescein angiography (FA), 124 eyes (54%) showed classic CNV outside the fovea on IA. One hundred and two of the 124 eyes (45%) underwent laser photocoagulation. We evaluated indocyanine green guided laser photocoagulation of extrafoveal CNV in 139 eyes. The success rate was 81% at 3 months after laser photocoagulation. This was estimated using timetable analyses to have decreased to 78% at one year and 71% at three years. Eighty percent of successfully treated eyes showed maintained or improved visual acuity. These results did not differ significantly from those obtained with laser photocoagulation based on FA findings. When classic CNV is not detected on FA, IA is indicated and if classic CNV is detected outside the fovea, photocoagulation should be performed aggressively. We compared the histological findings of removed subfoveal CNV with the IA findings prior to removal. IA findings of CNV before removal were divided into four types. Types I and II showed numerous vascular lumina in von Willebrand factor staining. Prominent proliferation in types I and II was demonstrated with Ki-67. Vascular endothelial growth factor (VEGF) showed strong staining in types I, II and III. Therefore, CNV in eyes with types I, II and III, and especially type I, requires urgent treatment. We compared visual outcomes one year after treatment between 52 eyes that underwent removal and 56 eyes that underwent laser photocoagulation of subfoveal CNV. When CNV size was one disc diameter or less, mean visual acuity, the percentage of eyes with improved vision and with a visual acuity of 0.1 or more, was significantly greater in operated eyes than in coagulated eyes. Removal is therefore superior to photocoagulation in subfoveal CNV of one disc diameter or less in size. We evaluated preoperative factors influencing the best corrected visual acuity at least six months after removal of subfoveal CNV in 67 eyes. Factors influencing the best corrected visual acuity were IA findings, feeder vessel ingrowth sites and CNV sizes. Good indications for removal included types I, II and III IA findings, extra foveal location feeder vessel ingrowth sites, and small CNV. III LOW VISION CARE: We performed reading tests using the MN read J chart for 90 eyes with the scar stage of CNV. Reading speed profiles of the 90 eyes were classified into two groups: 48 eyes showing a plateau with a relatively constant reading rate at the maximum level; and 42 eyes showing steadily increasing reading rate without a plateau. Eyes without a plateau had worse visual acuity, worse reading acuity, and slower reading speed. We evaluated newspaper reading performance by comparing conventional versus new methods based on the critical print size of the MN read J chart. Magnification power based on the critical print size were similar to those finally chosen as the best aid by the patients. On the other hand, magnification power was lower when conventional methods were used. The critical print size of the MN Read J chart appears to be valuable for determining low vision aids which facilitate reading by AMD patients. PMID- 11193944 TI - [New examination methods for macular disorders--application of diagnosis and treatment]. AB - To establish a diagnosis or evaluate the efficacy of treatment for macular disorders, we need methods to evaluate the anatomical and functional changes of these disorders. In this article, we describe several studies that we have conducted for 2 years. In section 1, we report our new methods for making a diagnosis and evaluating visual function in macular disorders. In section 2, we describe our trials of these examination methods in treatment. Here is the summary of our results. In section 1, to examine the structures of the macular area, we used a retinal thickness analyzer (RTA), a confocal scanning laser ophthalmoscope (Heidelberg Retina Tomograph, HRT), and optical coherence tomography (OCT) to measure retinal thickness and assess retinal microstructures. We compared retinal imaging analysis of various macular diseases obtained with these three instruments. With the RTA, we obtained good three-dimensional macular images displayed on a retinal thickness map, but the retinal thickness map did not demonstrate the thickened retina with dense retinal hemorrhages, and high backscattering from hard exudates might obscure the vitreoretinal interface. The HRT three-dimensional topographic image clearly showed the undulation of the retinal surface. However, it took a relatively long time to obtain the HRT image, and we sometimes could not obtain good topographic images because of fixation movement. Examination with the OCT allows confirmation of the retinal cross sectional structures, such as retinoschisis or cystoid spaces and the vitreomacular interface, such as vitreous traction, that cannot be detected using other conventional methods with high resolution, but high reflectivity from dense hemorrhages obscured the deeper layers of the retinal structures. Measurement of retinal thickness obtained with both the RTA and OCT is highly reproducible, and there was significant correlation between the retinal thicknesses measured with the two instruments. We believe that these three instruments might contribute significantly to early, accurate diagnosis and better monitoring of the therapeutic effects of vitrectomy for macular diseases. In the future, if these fundus imaging analysis instruments can achieve higher resolution and can analyze three-dimensional retinal images, they will provide better information to clinically evaluate macular diseases. We demonstrated vitreous examination and examination from the retinal surface to the deeper retinal layer at the macular area using a scanning laser ophthalmoscope (SLO). The SLO examination with an argon laser and a large confocal aperture was useful for conducting kinetic examination of the vitreous opacity above the macula. With a diode laser and a ring aperture (dark-field mode), it was possible to examine the retina from the deeper retinal layer to the choroids. On the other hand, the SLO also allows us to conduct a functional examination of fixation. We demonstrated that the referred retinal locus of fixation may change during the follow-up period in patients whose central fixation is impaired due to macular disease, and we showed that the fixation behavior was related to the visual acuity. Therefore, the SLO is an ideal instrument for determining the visual field and the visual acuity before and after treatment in patients with macular disease, because of its precise localization of the examination point by directly observing the fundus and by monitoring fixation behavior. Our new program installed in the SLO allows us to complete the quantitative retinal sensitivity evaluation within 2 minutes, which is difficult to do using a conventional SLO program. Furthermore, we demonstrated for the first time that minute functional changes in the retina can be detected by the SLO under low background illuminance. Such changes cannot be detected under conventional conditions. In addition, the extrafoveal visual acuity of normal subjects and patients with macular disease was studied using this new SLO program. The iso-acuity lines could be illustrated by summarizing these results in normal subjects. The SLO acuity of the horizontal meridian is significantly better than that of the vertical meridian, and even in the nasal area adjacent to the optic disc, an acuity of better than 0.1 could be achieved. To evaluate macular function, we also investigated the blood flow of the choroid (CF), the retina (RF), and the choriocapillaris at the fovea (CCF). We investigated the CF in patients with age-related macular degeneration (AMD) using pulsatile ocular blood flow (POBF) measurements. In patients with exudative AMD, the POBF was significantly lower than in patients with nonexudative AMD or in control subjects. Decreased CF may play a role in the development of choroidal neovascularization in AMD. RF was measured using laser Doppler velocimetry (LDV). (ABSTRACT TRUNCATED) PMID- 11193945 TI - [Macular diseases--application of automated static perimetry and optical coherence tomography]. AB - The usefulness of automated static perimetry and optical coherence tomography in the management of macular diseases has been described. Scotomata in eyes with central serous chorioretinopathy could be evaluated with central 10-degree automated static perimetry. The degree of visual field defects in eyes with the disease varied greatly with mean deviation of -10 dB or less in as many as 10% of the subjects. Although retinitis pigmentosa is a diffuse retinal dystrophy, eyes with a moderately advanced stage of retinitis pigmentosa should be managed as a macular disease, because the functioning retina is confined within the vascular arcade. The progressive nature in this stage of the disease could be demonstrated with a central 10-degree automated static perimetry measured once or twice a year and the use of univariate linear regression of mean deviation, in half of the patients with a mean follow-up period of 5 years. Functional recovery in eyes with exudative age-related macular degeneration after laser surgery or submacular surgery could be evaluated with central 10-degree automated static perimetry. Eyes with increased mean deviation in spite of reduced visual acuity after therapeutic intervention should also be evaluated. Macular function could also be evaluated using a color test. A newly developed color saturation discrimination test was applied to patients with age-related macular degeneration, retinitis pigmentosa, and cone dystrophy. The degree of dyschromatopsia was less in eyes with age-related macular degeneration than in those with retinitis pigmentosa or cone dystrophy with the same level of acuity loss. The highly protrusive nature of the orange-red nodule in eyes with idiopathic polypoidal choroidal vasculopathy was demonstrated with dimensional measurement with OCT. The degree of protrusion was greater than in eyes with serous pigment epithelial detachment, which suggests that the polypoidal lesion is covered with rigid tissues including Bruch's membrane. Parafoveal retinal sensitivity obtained with automated static perimetry was studied in correlation with retinal thickness measured using OCT in eyes with branch retinal vein occlusion showing macular edema without macular non perfusion or massive retinal hemorrhages. The increased retinal thickness due to macular edema is closely correlated with retinal sensitivity both at the fovea and in the parafoveal area. Eighty-nine phakic eyes of 46 patients with retinitis pigmentosa patients were studied to detect cystoid macular edema using OCT. Cystoid lesions were observed in the macula in 12 eyes in 6 (13%) of 46 patients. Some eyes with OCT-proven cystoid macular edema did not show dye pooling in the fluorescein angiogram. The width of the total area of cystoid lesions was positively correlated with best-corrected visual acuity but the thickness of the neurosensory retina at the center of the fovea was not. OCT findings of successfully repaired macular holes were categorized into 3 groups. Eyes with U type showed a normal foveal contour and a dark layer corresponding to the outer segment of photoreceptors. Eyes with V-type showed a notch in the surface of repaired neurosensory retina without a dark layer on the retinal pigment epithelium. Those with W-type showed a defect of the neurosensory retina, where the retinal pigment epithelium was exposed. The visual results were excellent in eyes with U-type, but poor in those with W-type. PMID- 11193946 TI - [Molecular cell biology on morphogenesis of the fovea and evolution of the central vision]. AB - Since Charles Darwin wrote "On the Origin of Species by Means of Natural Selection", it had been assumed that various eye types, from the compound eye to the camera eye, had originated independently in at least 40-60 different phyletic lines. However, the finding of Pax 6, the master control gene for eye morphogenesis, and the fact that its sequence is highly conserved throughout the animal kingdom indicated that the prototype eye in a primitive animal originated only once in evolution, and various eye types arose from the same origin. We recently found a Pax 6 mutation in a pedigree with foveal hypoplasia. Thus, the Pax 6 that appeared in light sensory cells of a primitive animal in ancient times may play a role in morphogenesis of the fovea, the most highly developed visual receptor. The fovea first appeared in evolution in the temporal retina of fishes. Then, in birds, the nasal fovea and bifoveal system with nasal and temporal foveas developed. The fovea disappeared in primitive mammals, and reappeared in primates. A residue of the fovea is conserved in the visual streak, and the disappearance and reappearance of the fovea, in primitive mammals and primates respectively, correlates with degeneration and restoration of cone pigment genes in photoreceptors. Humans inherited the temporal fovea that had first originated in fish eyes. Pax 6 is expressed in the entire eyeball at an early stage of development, and is also expressed widely in the retina to determine its differentiation. To determine the position of the fovea, retinal cells are abundant in the visual streak, probably because expression of Pax 6 is regulated by patterning of the dorsoventral axis of the eyeball. Signaling molecules, discharged from the front of the face, also regulate Pax 6 expression, and determine position of the fovea, visual axis, angle gamma, growth of the eyeball, and shape of the visual field. Further investigation of nerve pathfinding system from the fovea to the central nervous system will clarify the origin of the central vision, and contribute to human welfare. PMID- 11193948 TI - Partnership for Health and Accountability. Unique statewide partnership breaks ground on health care accountability. PMID- 11193949 TI - Answering the call for increased accountability. PMID- 11193950 TI - Challenges to HHS "conditions of participation" may be initiated in federal court. National Association of Psychiatric Health Systems v. Shalala. PMID- 11193951 TI - State enjoined from enforcing new drug price control law. Pharmaceutical Research and Manufacturer's Association of America v. Commissioner. PMID- 11193952 TI - Royston-based health care system honors the real "Georgia peach". PMID- 11193953 TI - A matter of public trust. PMID- 11193954 TI - Lexical, syntactic, and stress-pattern cues for speech segmentation. AB - Many sources of segmentation information are available in speech. Previous research has shown that one or another segmentation cue is used by listeners under certain circumstances. However, it has also been shown that none of the cues are absolutely reliable. Therefore, it is likely that people use a combination of segmentation cues when listening to normal speech. This study addresses the issue of how young adults use multiple segmentation cues (lexical, syntactic, and stress-pattern) in combination to break up continuous speech. Evidence that people use more than one cue at a time was found. Furthermore, the results suggest that people can use segmentation cues flexibly such that remaining cues are relied upon more heavily when other information is missing. PMID- 11193955 TI - Verb and noun morphology in the spoken and written language of children with language learning disabilities. AB - The purpose of this study was to investigate the use of verb and noun morphology in school-age children's spoken and written language. Sixty children, with and without language learning disabilities (LLD), each produced 2 spoken and 2 written language samples. The children's accuracy in using morphemes that mark verb finiteness (regular past tense, 3rd person singular present tense, copula, and auxiliary BE) was compared with their accuracy in using noun morphology (regular plural, possessive, articles). As would be expected, the typically achieving children, who were aged 7 to 12 years, had mastered the verb and noun morphology in spoken and written samples. The children with LLD, aged 10 to 12 years, also showed high accuracy in the spoken samples. On the other hand, they showed substantial difficulty in the written samples with the regular past tense, with errors in 26% of obligatory contexts. However, the children with LLD also had difficulty with the regular plural, with errors in 12% of obligatory contexts. For both the regular past tense and plural, all errors were errors of omission. These results indicate that finiteness marking remains an area of relative difficulty, but perhaps not the only grammatical difficulty, for children with language impairments in the school years. PMID- 11193956 TI - Factors affecting young children's use of pronouns as referring expressions. AB - Most studies of children's use of pronouns have focused either on the morphology of personal pronouns or on the anaphoric use of pronouns by older children. The current two studies investigated factors affecting children's choice of pronouns as referring expressions-in contrast with their use of full nouns and null references. In the first study it was found that 2.5- and 3.5-year-old children did not use pronouns differentially whether the adult (a) modeled a pronoun or a noun for the target object or (b) did or did not witness the target event (although there was evidence that they did notice and take account of the adult's witnessing in other ways). In the second study it was found that children of this same age (a) do not use pronouns to avoid unfamiliar or difficult nouns but (b) do use pronouns differently depending on the immediately preceding discourse of the experimenter (whether they were asked a specific question such as "What did X do?" or a general question such as "What happened?"). In the case of specific questions, children prefer to use a null reference but use some pronouns as well (almost never using full nouns); in the case of the generic questions, children use pronouns even more often (and use nouns more as well). This finding was corroborated by some new analyses of children's use of pronouns in specific discourse situations in previously published studies. These findings suggest that children's choice of pronouns as referring expressions in early language development is influenced more by the immediately preceding discourse than other kinds of factors. PMID- 11193957 TI - Spoken language production in Huntington's and Parkinson's diseases. AB - The purpose of this study was to investigate the presence and nature of spoken language deficits in Huntington's (HD) and Parkinson's (PD) diseases. Specifically, the study examined whether (a) the spoken language abilities of patients with HD or PD differ from those of age-matched control participants with no brain damage, (b) HD and PD are associated with similar spoken language profiles, and (c) the spoken language abilities of patients with HD or PD are related to the severity of their motor speech deficits, cognitive impairments, or both. All participants completed picture description tasks and a battery of cognitive and motor speech tests. Syntactic, quantitative, and informativeness measures of spoken language were analyzed. In terms of syntax, patients with HD produced shorter utterances, a smaller proportion of grammatical utterances, a larger proportion of simple sentences, and fewer embeddings per utterance than their non-brain-damaged peers. The HD group also produced utterances that were shorter and syntactically simpler than those of the PD group, despite similar performances on the cognitive and motor speech tests. The only syntactic difference between the PD group and their control group was that patients with PD produced a smaller proportion of grammatical sentences. Although the patient and control participants tended to produce similar amounts of verbal output, less of what the patients said was considered informative. Correlations between language measures and test battery results suggested that the spoken language abilities of patients with HD or PD are related to a variety of neuropsychological and motor speech changes. The implications of these findings for the clinical management of HD and PD are discussed. PMID- 11193958 TI - Use of temporal envelope cues by children with developmental dyslexia. AB - This study evaluates the ability to process auditory temporal-envelope cues in a group of 6 children with dyslexia (mean age: 10;10 years;months). To address this issue, we measured (a) temporal modulation transfer functions (TMTFs), that is, the detection thresholds of sinusoidal amplitude modulation (SAM) applied to a white noise carrier, as a function of modulation frequency, fm (fm was 4, 16, 64, 256, and 1,024 Hz) and (b) identification performance for vowel-consonant-vowel (VCV) stimuli over 5 sessions. VCV stimuli were either unprocessed or digitally processed to remove the original spectral information, resulting in a time varying speech envelope amplitude modulating a noise carrier. The same tests were conducted in 6 normal control children (mean age: 11;6 years;months) and 6 normal control adults (mean age: 24;8 years;months). SAM thresholds were similar in normal children and adults. For both normal groups, TMTFs were low pass in shape and showed low between-listener variability. TMTFs measured in children with dyslexia showed higher between-listener variability: TMTFs were band pass in 2 children, flat in 1 child, and low pass in the 3 others. Overall, SAM thresholds were higher in children with dyslexia than in normal children at fm = 4 and 1,024 Hz. Unprocessed-speech identification performance was nearly perfect in normal children and adults, and impaired in children with dyslexia. "Speech-envelope noise" identification performance was poorer in normal children and children with dyslexia than in normal adults. Performance improved across sessions in normal children and adults, but remained constant in children with dyslexia. Compared to normal children, children with dyslexia showed poorer reception of voicing, manner, and place of articulation for unprocessed speech and poorer reception of voicing for "speech-envelope noise." Taken together, these results support the hypothesis that some children with dyslexia may show abnormal auditory temporal envelope processing. Such a deficit, in turn, may explain the difficulties of children with dyslexia with speech perception. PMID- 11193959 TI - Multi-channel compression and speech intelligibility in industrial noise. AB - This study examined how various forms of compression affect speech intelligibility in moderately high levels of industrial noise. Thirteen listeners with high-frequency sensorineural hearing loss were fit with a digital hearing aid programmed to operate in three modes of compression: compression limiting, compression of low frequencies only (BILL), and compression of high frequencies only (TILL). For each of these conditions, listeners attempted to recognize CID W 22 monosyllabic words delivered in a background of recorded industrial noise. Word recognition was also measured in quiet for the compression-limiting condition. The highest word identification scores were obtained in quiet (80.9%). Of the three conditions in which background noise was present, the mean score was highest for TILL compression (52.4%), and lowest for BILL (39.7%). Representative time-weighted average (TWA) exposures for each of the aided noise conditions were determined by means of a procedure outlined previously by the first author. The projected 8-hour amplified TWA with the hearing aid programmed to the TILL configuration was 94 dBA, whereas TWAs for the linear and BILL configurations were each 104 dBA. Thus, the highest intelligibility and lowest noise exposures were obtained with the aid in the TILL mode. PMID- 11193960 TI - Perception of voiceless fricatives by normal-hearing and hearing-impaired children and adults. AB - This study examined the perceptual-weighting strategies and performance audibility functions of 11 moderately hearing-impaired (HI) children, 11 age matched normal-hearing (NH) children, 11 moderately HI adults, and 11 NH adults. The purpose was to (a) determine the perceptual-weighting strategies of HI children relative to the other groups and (b) determine the audibility required by each group to achieve a criterion level of performance. Stimuli were 4 nonsense syllables (see text). The vowel, transition, and fricative segments of each nonsense syllable were identified along the temporal domain, and each segment was amplified randomly within each syllable during presentation. Point biserial correlation coefficients were calculated using the amplitude variation of each segment and the correct and incorrect responses for the corresponding syllable. Results showed that for /see text/ and /see text/, all four groups heavily weighted the fricative segments during perception, whereas the vowel and transition segments received little or no weight. For /see text/, relatively low weights were given to each segment by all four groups. For /see text/, the NH children and adults weighted the transition segment more so than the vowel and fricative segments, whereas the HI children and adults weighted all three segments equally low. Performance-audibility functions of the fricative segments of /see text/ and /see text/ were constructed for each group. In general, maximum performance for each group was reached at lower audibility levels for /see text/ than for /see text/ and steeper functions were observed for the HI groups relative to the NH groups. A decision theory approach was used to confirm the audibility required by each group to achieve a > or =90% level of performance. Results showed both hearing sensitivity and age effects. The HI listeners required lower levels of audibility than the NH listeners to achieve similar levels of performance. Likewise, the adult listeners required lower levels of audibility than the children, although this difference was more substantial for the NH listeners than for the HI listeners. PMID- 11193961 TI - Age-related improvements in auditory backward and simultaneous masking in 6- to 10-year-old children. AB - This study investigated the development of auditory frequency and temporal resolution using simultaneous and backward masking of a tone by a noise. The participants were 6- to 10-year-old children and adults. On the measure of frequency resolution (the difference in the detection threshold for a tone presented either in a bandpass noise or in a spectrally notched noise), 6-year old children performed as well as adults. However, for the backward masking task, 6-year-olds had, on average, 34 dB higher thresholds than adults. A negative exponential decay function fitted to the backward masking data for subjects of all ages indicated that adult-like temporal resolution may not be reached until about 11 years of age. These results show that, measured by masking, frequency resolution has reached adult-like performance by 6 years of age, whereas temporal resolution develops beyond 10 years of age. Six-year-old children were also assessed with tests of cognitive ability. Improvements in both frequency and temporal resolution were found with increasing IQ score. PMID- 11193962 TI - Changes in normal speech after fatiguing the tongue. AB - Detrimental effects of tongue fatigue on speech have been assumed to exist based on neuromotor speech disorders. However, to address whether fatigue is a contributing cause to impaired speech requires an experimental protocol with an uncomplicated population. This study induced tongue fatigue in eight neurologically normal persons and examined changes in speech perceptually and acoustically. The fatigue task consisted of repeated cycles of 6 s of sustained maximum voluntary contraction and 4 s of rest until 50% of maximum strength could not be achieved for three consecutive cycles. Participants then produced speech that was weighted heavily with lingual-palatal consonants. Perceptual analyses of the speech revealed a statistically significant deleterious effect of induced tongue fatigue on speech precision and an incomplete reversal of this effect after a recovery period. Acoustically, the first and third spectral moments (mean and skewness) of the spectral energy for /see text/, /see text/, and /see text/ differed significantly after fatigue but in directions opposite to a priori predictions. Tendencies were found for decreased stop-closure duration and increased voice onset time for /see text/ after fatigue. Supplemental analyses revealed decreased second formant (F2) frequency for /see text/ and /see text/ and flattened F2 transition for the diphthong /see text/ after fatigue. These results indicate disruption of tongue positioning and transitioning for lingual palatal consonants during speech after prolonged strenuous tongue exercises. PMID- 11193963 TI - Disfluency and time perception. AB - Stuttering is manifested as a disruption in speech timing, but it may stem from a more basic temporal disorder (R. D. Kent, 1984). We compared the ability of stuttering and nonstuttering adults to estimate protensity and to distinguish the relative lengths of short tones. We also examined whether there is a correlation between a person's degree of disfluency and the ability to measure protensity or judge the relative lengths of short tones. Twenty stuttering and 20 nonstuttering adults were given the Duration Pattern Sequence Test. They were also asked to estimate the lengths of 8 tones and silent intervals. A negative correlation was found between degree of disfluency and ability to determine the relative lengths of short tones. A positive correlation was found between degree of disfluency and length of protensity estimates. PMID- 11193964 TI - Treating stuttering in young children: predicting treatment time in the Lidcombe Program. AB - It is known that children may recover from stuttering without formal treatment during the first years after onset. Consequently, the timing of professional, early stuttering intervention is a pressing issue in speech-language pathology. This report presents data pertinent to this issue for 261 preschool-age children who received the Lidcombe Program of early stuttering intervention. Of these children, 250 completed the program and were considered by their clinicians to have been treated successfully. For the children who were treated successfully, logistical regression analyses were used to determine whether age, gender, period from onset to treatment, and stuttering severity related systematically to the time required for treatment. The present data confirmed previous reports that a median of 11 clinic visits was required to achieve zero or near-zero stuttering with the Lidcombe Program. Results were also consistent with a preliminary report of 14 children (C. W. Starkweather & S. R. Gottwald, 1993) showing a significant relation between stuttering severity and the time needed for treatment, with children with more severe stuttering requiring longer treatment times than children with less severe stuttering. However, results did not associate either increasing age or increased onset-to-treatment intervals with longer treatment times. This finding is not consistent with the Starkweather and Gottwald report, which linked advancing age with longer treatment time. In fact, the present data suggest that, for a short period after stuttering onset in the preschool years, a short delay in treatment does not appear to increase treatment time. An important caveat to these data is that they cannot be generalized to late childhood or early adolescence. The present findings are discussed in relation to natural recovery from stuttering. PMID- 11193965 TI - Perceptual-phonetic predictors of single-word intelligibility: a study of Cantonese dysarthria. AB - This study investigated the perceptual-phonetic predictors of intelligibility in Cantonese speakers with dysarthria. The speakers were 20 young adults with cerebral palsy. The listener group consisted of 12 native Cantonese speakers. A single-word intelligibility test was constructed, based on 17 phonetic contrasts. There were no significant differences in intelligibility for gender, age, or type of cerebral palsy. A regression analysis showed that intelligibility could be predicted with 97% accuracy by 5 out of the 6 most problematic contrasts. Three contrasts (glottal vs. null, final vs. null, and long vs. short vowel) predicted variation on an independent intelligibility measure obtained for the same speakers with 84% accuracy. Principal components analysis derived 4 components, which accounted for 81% of the variance in the 17 contrasts. Physiological explanations and language-specific contributions to speech disorder in this group of speakers are discussed. PMID- 11193966 TI - An acoustic study of coarticulation in dysarthric speakers with Parkinson disease. AB - Anticipatory vowel coarticulation in obstruent + vowel syllables was studied for 9 dysarthric males with mild to moderate idiopathic Parkinson disease (PD) and a group of 10 healthy males. In addition to studying coarticulatory differences for speakers' habitual rate repetitions, a graded speaking rate task was used to investigate the effect of rate variation on coarticulation. The ratio of F2 onset frequency/F2 target frequency was used to infer coarticulation (i.e., ratios of 1.0 indicate complete vowel harmony at vowel onset, and ratios greater than 1.0 indicate relatively less coarticulation). Because F2 onset frequency is a relatively novel measure of coarticulation, a more common measure of anticipatory vowel coarticulation-fricative F2-was obtained for a subset of the speech stimuli and compared to F2 onset measures. Ratios of fricative F2/F2 target frequency also were computed to infer coarticulation and the results were compared to the F2 onset/F2 target ratios. The results indicated a modest relationship between F2 onset frequency and fricative F2 for both speaking tasks and speaker groups, with a stronger relationship for the graded rate task. Regression analyses for the graded rate task further indicated that longer vowel durations were associated with larger ratios for both speaker groups. Thus, coarticulation tended to increase with faster rates and decrease with slower rates, although the relationship was more systematic for control speakers. Ratios for the habitual task tended to be smaller for speakers with PD, suggesting increased coarticulation relative to control speakers. This effect was not entirely attributable to the more rapid speaking rates for speakers with PD. Because habitual rate F2 onset/F2 target ratios tended to underestimate the extent to which coarticulation was increased for speakers with PD-compared to the fricative F2/F2 target ratios-measures other than F2 onset should be used to infer absolute differences in extent of coarticulation for speakers with PD and healthy controls. PMID- 11193967 TI - Motor strategy in rapid sequential swallowing: new insights. AB - This study examined the physiological properties and movement strategies of normal, rapid sequential swallowing during simultaneous videofluoroscopy (VFS) and submental surface electromyography (EMG). Ten subjects performed discrete (5 and 15 cc) and sequential (150 cc in tilted and upright head postures) swallowing tasks. Analyses included VFS event timing, movement/bolus passage characteristics, EMG amplitude waveforms, and peak and offset EMG amplitudes. Results revealed that sequential swallows were significantly shorter than discrete swallows in several VFS event durations, but significantly longer in pharyngeal transit and stage transition times. The hyolaryngeal system exhibited a cyclical "rise and partial fall" movement pattern during sequential swallows on VFS, corresponding to a repetitive "activation and partial deactivation" characteristic on EMG. Greater peak EMG amplitude for sequential than discrete swallows was found in 6/10 subjects. Pharyngeal bolus merging, preparatory laryngeal gestures, and penetration without aspiration were also observed in some subjects on VFS. Intersubject differences were significant in timing measures and EMG amplitude. Our findings of individual variability and subject-specific strategies for task accommodation support the notion of built-in plasticity in the deglutitive motor complex. PMID- 11193968 TI - Multivariate statistical analysis of flat vowel spectra with a view to characterizing dysphonic voices. AB - The aim of this article is to show how dysphonic voices can be characterized by means of a multivariate statistical analysis of flat vowel spectra. The spectral contour was obtained by means of a wavelet transform of the logarithmic magnitude spectrum, which was subsequently flattened to remove interspeaker variability related to the excitation and vocal tract filter functions. The results of the statistical analysis of flat spectra were the following. Firstly, principal components analysis produced markers that separated noisy from clean spectra. Secondly, the heuristic search for harmonic peaks or interharmonic dips could be omitted. Thirdly, conventional spectral markers of noise appeared as special instances of the markers that were derived statistically. Fourthly, the levels of visually assigned hoarseness and the first two principal components were significantly correlated. The assignment of different levels of (visual) hoarseness to different vowel timbres could be explained by the variability associated with the spectral contour. PMID- 11193969 TI - A comparison of speech training methods with deaf adolescents: spectrographic versus noninstrumental instruction. AB - The effects of speech training with real-time spectrographic displays (SDs) were examined and compared to the effects of noninstrumental (NI) instruction (i.e., training without computerized displays of speech) for deaf adolescents. A single case modified alternating-treatment experimental design with replication across subjects and speech targets was used to examine within-subject performance in establishing, maintaining, and generalizing target consonants. Comparisons between the two approaches were accomplished by determining how frequently each method resulted in improvement, maintenance of improvement, and generalization to untrained words. Each of the 4 subjects demonstrated improvement under both forms of instruction in a relatively short time. Maintenance of improvement was observed 6 weeks post-treatment for two NI-trained targets and one SD-trained target. Two subjects showed better generalization for their SD-trained target than their NI target. There was little difference in generalization scores for the remaining subjects. All subjects either regained their highest previous levels of acceptability or maintained high-level acceptability following brief, independent practice with SDs 10 weeks after training was discontinued. The expediency of independent practice with SDs was discussed. PMID- 11193970 TI - Variations in the relative speeds of orofacial structures with stuttering severity. AB - Stuttering can be characterized in part as a disorder in the coordination of different muscle systems. In light of basic aspects of orofacial physiology and development, the speeds of the lips and tongue relative to the jaw may be an important dimension for evaluating motor coordination among persons who stutter (PWS). To test this idea, an electromagnetic system was used to obtain measures of lip, tongue, and jaw speed in 38 adults (29 PWS and 9 normally fluent speakers, NFS) as they repeated a simple speech utterance at a normal rate. Using categorical ratings of stuttering severity, ratios of tongue speed to jaw speed were significantly greater in PWS rated as severe, compared to NFS and other PWS. Significant increases in lower lip-to-jaw and tongue-to-jaw speed ratios with stuttering severity were also reflected in correlation analyses relating speed ratios to a continuous measure of stuttering severity. These trends in speed ratio were related to increases in lower lip and tongue speed and decreases in jaw speed with stuttering severity. Sources of the speed differences are discussed in relation to underlying muscle activity, motor compensation processes in adults, and the development of orofacial motor control in children who stutter. PMID- 11193971 TI - Does the respiratory system function as an active pressure-flow source during experimental venting of oral air pressure? Comments on Finnegan, Luschei, and Hoffman (1999). PMID- 11193972 TI - Performing a quality semen analysis in the clinical laboratory. PMID- 11193973 TI - Nutrition assessment outcomes: a protocol for Native American hospitals. AB - The incorporation of visceral protein testing into nutrition assessment protocols can help all hospitals rapidly and accurately identify patients in need of restorative nutrition therapy. Reilly showed that a 3- to 5-day delay in identifying malnutrition has a direct variable cost of $1,500 per case. Studies by Brugler, Mears, and Reilly have demonstrated longer lengths of stay and increased care costs because of nosocomial complications (i.e., infections, pressure ulcers, wound dehiscence, dyspnea, system failures) related to malnutrition. Brugler showed that functionality--a measure of a patient's independence and ability to perform daily activities--both at admission and discharge, the number of care interventions, the occurrence of complications, the level of nutrition treatment needed, and the patient's discharge disposition were strongly associated with their admission albumin value. Conversely, nutrition restoration leads to improved patient outcomes, reduced costs, maximization of care reimbursement, and fulfillment of regulatory requirements. Adoption of this protocol by other hospitals should allow them to demonstrate comparable results, thereby justifying the incorporation of visceral protein testing into their nutrition assessment methods. PMID- 11193974 TI - Point-of-care testing. AB - Is POCT worth integrating into a facility? Despite its promise of speed and convenience, this technology requires careful evaluation of potential benefits, disadvantages, and challenges to the existing system. If the pros outweigh the cons, a step-by-step approach can ease the process of implementing a POCT program. PMID- 11193975 TI - Measuring ionized magnesium in complex physiological solutions. PMID- 11193976 TI - HIV's pharmacokinetics, pharmacodynamics, pharmacogenetics, and pharmacogenomics. PMID- 11193977 TI - Automated immunoassay of ANA and dsDNA autoantibodies in human serum samples. PMID- 11193978 TI - Use of a high-sensitivity C-reactive protein assay in evaluating cardiovascular disease risk. PMID- 11193980 TI - Laboratory results in real-time via the Web. PMID- 11193979 TI - Extending disease management: a home monitoring system for vital signs. PMID- 11193981 TI - An improved diabetes diagnostic kit with desiccant. PMID- 11193982 TI - Give families credit, access. PMID- 11193983 TI - Hill Physicians--the impact of the Internet on an IPA. Case study 2. PMID- 11193984 TI - Supply capitation. Proving ground. PMID- 11193985 TI - Herbal supplements. Potion patrol. PMID- 11193986 TI - Scripps Health--using technology to reinvent itself. Case study 3. PMID- 11193987 TI - Reducing stroke deaths. Stroke of genius. PMID- 11193988 TI - Used medical equipment. Old stuff is us. PMID- 11193989 TI - E-ICU. Hands-off care. PMID- 11193990 TI - HIPAA is not Y2K. PMID- 11193991 TI - Consumers in control. How the Net will reshape health care. AB - Two trends are converging upon the health care landscape. And the collision of these two forces may change the health care system forever. Consumerism, a trend challenging every industry throughout the nation, is magnified in health care by simple demographics. The baby boomers, the most demanding consumers history has ever known, are entering the age of high health care use en masse. They will not be denied. Meanwhile, the development of the Internet--combined with the explosion in its use--has created a medium that has the force to change industries. PMID- 11193992 TI - Big ideas. Technology: crossed wires. PMID- 11193994 TI - Big ideas. Consumerism: who's buying it? PMID- 11193993 TI - Big ideas. Genomics: delayed reaction. PMID- 11193995 TI - Big ideas. Wild cards: surprises? You bet. PMID- 11193996 TI - Allina Health--a lesson in strategy. Case study 1. PMID- 11193997 TI - Kinder caring. PMID- 11193998 TI - Seroprevalence of Chlamydia pneumoniae infection in Thailand. AB - Chlamydia pneumoniae (C. pneumoniae) is an emerging infectious agent, with a spectrum of clinical manifestations, and it has recently been tentatively linked to atherosclerosis. In order to describe the seroprevalence of C. pneumoniae in Thailand, we evaluated 1,798 normal healthy subjects (aged 20-93 years) for anti C. pneumoniae IgG and IgA. Specific antibodies were measured by the fully automated ELISA method using elementary bodies of C. pneumoniae as an antigen. IgG antibodies against C. pneumoniae were presented in 55.16 per cent of men and 41.63 per cent of women. Anti-C. pneumoniae IgA were presented in 31.50 per cent of men and 27.49 per cent of women. The prevalence of IgG antibody increased with age and reached 78 per cent in subjects between 51-93 years. The pattern of IgA antibody was a saddle shape, which indicated 2 peaks of chronic infection. Our results suggested that C. pneumoniae infection was common in Thailand. The high prevalence of evidence of exposure to C. pneumoniae may have implications for the prevention of cardiovascular disease if further study concludes that infection with this organism is a risk for cardiovascular disease. PMID- 11193999 TI - Comparison of parathyroid hormone in angiographically-demonstrated coronary artery disease patients and healthy Thais. AB - Parathyroid hormone (PTH) influences the calcium metabolism. The idea of cardiovascular effects of PTH is not new. Target cells for PTH are cardiomyocytes and smooth muscle cells. Evidence from previous studies suggest that many patients with heart disease have elevated PTH concentrations. Our objective was to determine PTH status in patients with coronary artery disease (CAD). We compared intact PTH levels in 109 CAD patients with 103 healthy people by electrochemiluminescence immunoassay. Mean values of PTH in healthy Thais and CAD patients were 37.4 +/- 17.9 and 40.2 +/- 21.8 respectively. No statistical difference was shown. In addition, we compared PTH levels among various numbers of coronary occlusion and also found no differences. We propose that intact PTH concentrations in CAD patients are not higher than in the healthy population. PMID- 11194000 TI - Limitation of transthoracic echocardiography in the diagnosis of congenital heart diseases. AB - Nowadays, it has been widely accepted that echocardiography is the most efficient, non invasive diagnostic tool to diagnose congenital heart diseases. However, cardiac catheterization remains the gold standard to diagnose and obtain hemodynamic data prior to cardiovascular surgery. In order to find out the accuracy of transthoracic echocardiography in relation to the anatomical diagnosis of congenital heart diseases, 175 consecutive patients who underwent diagnostic cardiac catheterization during January 1999 to December 1999 were reviewed. All of them had complete echocardiographic studies prior to the procedure. The male to female ratio was 1.06:1. The median age at the time of echocardiography was 3.36 (0.01-28.8) years old. The indications of the cardiac catheterization were to demonstrate cardiovascular anatomy 64 per cent, to obtain pulmonary artery pressure and pulmonary vascular resistance 13.7 per cent, and to get both information 22.3 per cent. Tetralogy of Fallot (23.4%) was the most frequent cardiac malformation, followed by complex congenital heart diseases (22.3%), simple left to right shunt (12%), pulmonary atresia with ventricular septal defect (8.6%), tricuspid atresia (5.7%), simple d-transposition of great arteries (4%), etc. From cardiac catheterization; 49 cases (28%) revealed additional data which were surgically important, 3 cases (1.7%) resulted in different diagnoses, and 3 cases (1.7%) revealed additional information which was not surgically important. Inadequate imaging technique (36 cases, 65.5%) and limitation of technique (19 cases, 34.5%) were the reasons for missing anatomical findings of transthoracic echocardiography. Age at the time of echocardiography was not a significant factor affecting the accuracy. Persistent left superior vena cava, multiple aorto-pulmonary collateral arteries, pulmonary artery anatomy, and coronary artery anatomy were the most frequent cardiac lesions misdiagnosed by transthoracic echocardiography that were somewhat surgically important. The incorrect echocardiographic diagnoses were aorto-pulmonary window, patent ductus arteriosus, and vascular ring. Thorough and extensive echocardiographic scanning coupled with cooperative or adequately sedated patients by an experienced operator using an efficient echocardiographic machine might improve the accuracy of transthoracic echocardiography in the diagnosis of congenital heart diseases. PMID- 11194001 TI - Comparison of supraventricular tachycardia from concealed bypass tract and Wolff Parkinson-White syndrome. AB - Supraventricular tachycardia (SVT) is a common problem. There are 2 types of accessory atrioventricular pathway (AP) causing SVT: one can conduct antegradely (WPW syndrome) and another can conduct only in a retrograde direction (concealed bypass tract or CBT). There are little data of the significance and difference of the two types in Thailand. The objectives of this study were to compare characteristics of patients, accessory pathways and outcome of radiofrequency catheter ablation (RFCA) between the 2 types of accessory pathways. We reviewed the electrophysiology report of patients with supraventricular tachycardia from the accessory pathway who were referred for RFCA. There were 74 males and 74 females at a mean age of 37 years. CBT accounts for 44 per cent of SVT from AP. Compared to CBT, WPW syndrome was more in the right-sided location, more associated with heart disease, a higher number of accessory pathways, more inducible atrial fibrillation and more difficult to do ablation. However, the overall success rate of RFCA was similar. Although the recurrence rate was 8.4 per cent, all patients with recurrence were successfully reablated. We concluded from this study that RFCA is a highly effective method for the treatment for both forms of accessory pathway although there are some differences between WPW syndrome and CBT. PMID- 11194002 TI - Effect of atenolol on symptomatic ventricular arrhythmia without structural heart disease. AB - Ventricular arrhythmia (VA) from right ventricular outflow tract (RVOT) is a common problem. Symptomatic patients are usually treated with beta-blockers. There is little data on the systematic evaluation of the drug efficacy. The objectives of this study were 1) To determine proportion of exercise induced ventricular arrhythmia among patients with symptomatic ventricular arrhythmia and 2) to determine the response to beta blockers and the correlation between the response to betablockers and exercise induced VA. We prospectively studied 46 consecutive patients with symptomatic ventricular arrhythmia. Patients recorded their symptom scores underwent exercise testing and 24-hour ambulatory monitoring before treatment and 1 month after atenolol. Exercise induced ventricular arrhythmia was demonstrated in 28 per cent of patients with symptomatic ventricular arrhythmia. Atenolol improves symptoms, decreases PVC count from ambulatory monitoring, increases exercise duration and suppresses malignant form of VA during exercise. These effects are at a similar extent in both groups of patients: those with and without exercise induced VA. However, the effect on ventricular arrhythmia suppression during exercise of atenolol was seen only in patients with increased PVC during exercise. In conclusion, atenolol is a good option in treating patients with symptomatic VA from RVOT regardless of the pattern of PVC response to exercise. Atenolol can suppress PVC during exercise testing better in patients with exercise induced VA compared to those without. PMID- 11194003 TI - Biochemical markers of bone turnover in angiographically-demonstrated coronary artery disease patients and healthy Thais. AB - The patients with coronary artery disease (CAD) were suffering from dyspnea. Physical activity of these patients was limited. Their lifestyle may be contributory factors for osteoporosis. Recent research has shown that biochemical markers may be used to predict future bone loss and identify individuals at risk for osteoporosis. Our objectives were to estimate reference ranges of bone markers in healthy Thais and to compare bone turnover between 105 healthy people and 118 CAD patients by using biochemical markers of bone formation and resorption. Mean values of bone markers in controls and patients were 22.9 +/- 12.9, 21.6 +/- 16.2 respectively for N-Mid osteocalcin and 0.45 +/- 0.30, 0.47 +/ 0.37 respectively for beta-Crosslaps. There was no statistical difference of N Mid osteocalcin (p=0.50) and beta-Crosslaps (p=0.64) values between groups. Our data from this study suggested that that CAD patients have no higher risk for osteoporosis than healthy people. PMID- 11194004 TI - Reliability of Thai version of SF-36 questionnaire for the evaluation of quality of life in cardiac patients. AB - Quality of life is an important measurement of medical outcomes. Reliability of a Thai version of the SF-36 questionnaire has never been reported. The objective of this study was to determine the reliability of a Thai version of the SF-36 questionnaire in cardiac patients. We developed a Thai version of the SF-36 questionnaire and tested it in 212 cardiac patients. Reliability of the Thai version of the SF-36 questionnaire was assessed by internal consistency using Cronbach's Alpha statistic and inter-item correlation. We demonstrated that Cronbach's Alpha coefficient of every aspect of QOL exceeded 0.7, and all inter item correlation exceeded 0.4. In conclusion, the Thai version of the SF-36 questionnaire is a valuable tool in assessing medical outcomes and medical research in Thai patients with cardiac disease. Whether it can be used in other diseases remains unknown. PMID- 11194005 TI - The use of cardiac magnetic resonance imaging in coronary artery disease. AB - A new noninvasive imaging technique, magnetic resonance imaging (MRI), has been developed that has the potential to assess anatomical and functional data of patients with coronary artery disease. None of the other cardiac investigations to date can combine all aspects of information. Cardiac MRI is a challenging task because of the motion of the structure during cardiac contraction and the motion with respiration. We reviewed the technique and the use of cardiac MRI in various aspects. The emerging area in cardiac MRI is the analysis of the plaque morphology information, and the use of the new contrast agents. Further investigation is needed in order for cardiac MRI to achieve a better image information within a shorter period of time. PMID- 11194006 TI - Impaired fasting glucose, diabetes mellitus and coronary risk factors. AB - The authors conducted a prevalence survey of impaired fasting glucose and diabetes mellitus in 3,615 Shinawatra employees, and we also determined various risk factors of coronary artery disease such as blood pressure level, body mass index and serum lipids. The prevalence of impaired fasting glucose and diabetes mellitus were 1.7 per cent and 0.8 per cent respectively. The prevalences were more common in males and increased with increasing age. Coronary risk factors were higher in impaired fasting glucose (IFG) and diabetes mellitus (DM) when compared with normal glucose levels. There were also significant differences between impaired fasting glucose and diabetes mellitus, except for pulse pressure, serum cholesterol level, LDL-cholesterol level and HDL-cholesterol level. PMID- 11194007 TI - Regular exercise and cardiovascular risk factors. AB - Physical inactivity has been counted as a risk factor for coronary artery disease. Regular exercise has also been reported to reduce risk of cardiovascular disease and its risk factors. We surveyed 3615 subjects for their conventional risk factors of coronary disease and for the frequency of their exercise. We found that subjects who had regular exercise were more likely to have lower triglyceride and resting heart rate. HDL cholesterol was higher in the group of subjects who had regular exercise. There was no difference in fasting plasma glucose, total cholesterol or blood pressure levels between those who had and those who did not have regular exercise. PMID- 11194008 TI - Electromagnetic interference of permanent pacemakers by mobile phones in Thailand. AB - The possible permanent pacemaker function interference by mobile telephones is concerned worldwide. Previous studies from the other countries with different mobile telephone systems and permanent pacemakers provided useful but indirect information. We in vitro studied the interaction between local mobile telephones and permanent pacemakers in Thailand. Seventeen mobile telephones from different systems and brands were tested in the laboratory with seven permanent pacemakers from different companies. We found no interference in the function of permanent pacemakers. The application of the information may be limited from the in vitro nature of the study. However this would be the useful reference for the future in vivo study. PMID- 11194009 TI - Are routine checkups necessary?: The Shinawatra's employee study. AB - The authors performed a survey in 3,615 Shinawatra employees aged 18-60 years to determine the abnormalities found with routine checkup. The annual checkup included: history taking. anthropometric measurement, physical examination, complete blood count, urine analysis, chest roentgenography, blood chemistry (fasting blood glucose, BUN, creatinine, uric acid, AST/ALT, cholesterol, triglyceride and HDL-cholesterol). The prevalence of abnormalities with management change detected by complete blood count, urine analysis was low and we did not recommend the routine use of complete blood count and urine analysis. The prevalence of hypertension was more common in males and the prevalence increased sharply after the age of 25 years in males and 40 years in females. The prevalence of abnormalities of BUN, creatinine (both males and females) and uric acid (in females) was very low. There was high prevalence of high AST/ALT which suggested hepatitis in our population, and the prevalence was more common in males beginning at a young age. Diabetes mellitus was more common in males especially after the age of 45 years. Chest roentgenography abnormalities were found in 9.4 per cent and the prevalence of abnormalities increased with age and was common after the age of 44 years. Most of the abnormalities found by chest roentgenography were pulmonary infiltration and cardiomegaly. The authors' findings did not recommend the routine use of complete blood count, urine analysis, fasting BUN and creatinine. We recommend routine blood pressure measurement in males aged 25 years or more and in females aged 40 years or more. We suggest routine blood cholesterol measurement in both sexes, blood triglyceride measurement in males aged 25 years or more and fasting blood sugar tests in males aged more than 44 years, chest roentgenography in males and females after the age of 45 years. PMID- 11194010 TI - Prevalence of new coronary risk factors in Thai population. AB - Many new cardiovascular biomarkers of atherosclerosis have recently been emerging. However, there is a paucity of these data in the Thai population. This study aims to determine the prevalence of these biomarkers of atherosclerosis and the relationship between these new risk factors and other conventional risk factors for atherosclerosis in the healthy Thai population. As a yearly check-up program, we surveyed 3,615 normal healthy populations for their conventional risk factors and some new cardiovascular biomarkers for atherosclerosis. The authors found hyperhomocysteinemia and high level of Lp(a) in 27 per cent and 32 per cent of the cases respectively. Prevalence of recent and past chlamydial infection was found in 30 per cent and 51 per cent respectively. PMID- 11194011 TI - Acute and follow-up results of laser angioplasty: single center experience. AB - Excimer laser angioplasty was used to treat total occluded coronary arteries and instent restenosis lesions with high success rate. To assess immediate and long term results of patients treated with excimer laser, we analyzed demographic information and the immediate results of 44 patients who underwent ELCA. The patients were followed up and assessed for clinical restenosis. The initial success rate of ELCA was 86.4 per cent which is comparable to plain balloon angioplasty performed during the same period. Clinical restenosis was 29 per cent. In conclusion, ELCA for patients with coronary artery disease can be performed with initial high success rate and reasonable long-term restenosis. PMID- 11194012 TI - The use of nonfluoroscopic catheter-based mapping system to perform radiofrequency ablation in complex ventricular tachycardia after cardiac surgery in congenital heart disease: a case report. AB - A nonfluoroscopic electroanatomical cardiac mapping system (CARTO) integrates anatomical and electrophysiological information to reconstruct a three dimensional activation map. Information from the CARTO system helps to reveal the mechanism and perform successful ablation in scar re-entry ventricular tachycardia after cardiac surgery. Three-dimensional activation and propagation mapping was performed in a patient with ventricular tachycardia after surgical correction of a double outlet right ventricle. The ventricular tachycardia appeared in two morphologies and were refractory to antiarrhythmic medication including amiodarone. Both ventricular tachycardias were re-entered using the ventriculotomy scar but rotated in different directions. Successful radiofrequency ablation was performed by creating a line of conduction block from the pulmonic valve to the ventriculotomy scar using entrainment mapping and the ablation lesion tagging technique. The CARTO system is useful in mapping and guiding the ablation of complex ventricular tachycardia after surgical correction in congenital heart disease PMID- 11194013 TI - Polymorphism of the gene encoding lipoprotein lipase in thai primary hyperlipoproteinemias. AB - Lipoprotein lipase (LPL) plays a central role in the clearance of very low density lipoprotein (VLDL) and chylomicrons from the circulation. It also affects the maturation of high density lipoprotein (HDL) and low density lipoprotein (LDL). LPL is an important candidate gene in determining the risk factor in metabolic disorders including primary hyperlipidemia. Our study is the first report from Thailand on the characterization of two common DNA polymorphisms, i.e Pvu II and Hind III at introns 6 and 8, respectively of the LPL gene in 94 Thai dyslipidemic subjects compared to 32 normolipidemic subjects using PCR-RFLP. It was observed that the frequencies of the cut and uncut alleles of Pvu II were 0.67 and 0.33 in normolipidemic subjects. Such frequencies were 0.64 and 0.36 in hyperlipidemic subjects. Additionally, the frequencies of the cut and uncut alleles of Hind III were found to be 0.73 and 0.27 in normolipidemic subjects. They were 0.85 and 0.15 in hyperlipidemic subjects. The allele frequencies of the Hind III but not Pvu II polymorphism in hyperlipidemic subjects were significantly different from normolipidemic subjects (p<0.05). The relation between these polymorphisms and lipid traits was not statistically significant (p>0.05). PMID- 11194014 TI - Correlation of serum lipoprotein(a) with the clinical presentation of Thai coronary artery disease patients. AB - Elevated serum levels of lipoprotein(a) [Lp(a)] confer an increased risk of coronary artery disease (CAD) and have been confirmed as a strong and independent risk factor for this disease. This case-control study was to determine the significance of elevated Lp(a) levels for the existence of CAD by systematically recording cardiovascular risk factors in diagnostic coronary angiography in a group of patients. Two hundred thirty seven consecutive patients (175 men, 62 women, aged 61+/-10 years) which comprised 24 acute myocardial infarction (AMI), 76 unstable angina (UA) and 137 stable angina (SA) who underwent coronary angiography, were used as cases. One hundred seventy normal healthy volunteers (95 men, 75 women, and aged 58+/-15 years) were used as controls. Lp(a) concentration were measured by an immunoturbidimetric method (Roche Diagnostics, Switzerland). There was a significant difference between Lp(a) levels in UA compared with the control subjects (44.2+/-49.0 vs. 27.6+/-25.3 mg/dL, p = 0.0006). When we compared SA and the control group (35.6+/-31.3 vs. 27.6+/-25.3 mg/dL, p = 0.0139) there was a significant difference between these two groups. UA patients also had a significantly higher prevalence of abnormal Lp(a) (>30 mg/dL) compared with the normal healthy control group (43.2% UA vs. 28.8% control, OR = 1.90, 95%CI = 1.08-3.32, p = 0.0248). SA patients also had the same finding as UA patients in a higher prevalence of abnormal Lp(a) when compared with the control group (45.2% SA vs. 28.8% control, OR = 2.04, 95%CI = 1.27-3.27, p = 0.0028). These data further support the role of Lp(a) in atherosclerotic coronary disease and the pathogenesis of acute coronary syndromes. PMID- 11194015 TI - Percutaneous transluminal coronary angioplasty in the young patients--Siriraj Hospital's experience. AB - The aim of this study was to follow-up immediate and long term results of patients aged less than 40 years with CAD treated by PTCA. Primary end points were to record major coronary events, incidence and timing of restenosis and requirement of repeated revascularization after initial PTCA. Data was collected retrospectively from records of patients aged less than 40 years who underwent PTCA from Jan 1996 to June 1998 in Her Majesty Cardiac Center, Siriraj Hospital. Patients were followed up and data was collected regarding recurrent angina, major coronary events and results of repeated coronary angiography and revascularization if available. Out of 830 procedures performed for 325 patients, 30 patients (9%) were less than 40 years of age and comprised of 26 males (87%) and 4 females (13%). Eighteen patients (60%) had more than one risk factor. The most important risk factor was smoking (60%) followed by dyslipidaemia (47%) and family history of coronary artery disease (20%). DM was strikingly uncommon. 14 patients had single vessel disease and 16 patients had multiple vessel disease. Initial stenosis was 87.5 +/- 9.8 and residual stenosis was 17.8 +/- 10.8. PTCA failed for 5 lesions, overall success rate was 89 per cent. Stent was used for 12 lesions in 10 patients. There was no major complication during the procedure. Minor complications included non occlusive dissection in four cases and groin haematoma in three cases. The follow up ranged from 7-36 months with the median of 23 months. During follow up, there was no major cardiac event such as death, acute MI, congestive heart failure or cerebero-vascular accident. Eleven patients (37%) had sustained improvement without recurrent angina. Recurrent angina occurred in 19 patients (63%) after initial PTCA and second/third recurrent angina occurred in 5 patients. On repeated coronary angiography angiographic restenosis was seen in 10 patients (33%) after initial PTCA. Overall repeated revascularization was done twenty times for sixteen patients which included 4 CABGs and 16 PTCA. Twenty one patients (70%) showed sustained improvement after repeated PTCA and medications. Follow up results of PTCA in young patients showed sustained improvement but achieved at high rate of repeated revascularization. PMID- 11194016 TI - Biosense mapping for ablation of ventricular tachycardia in cardiomyopathy. AB - Using conventional technology, radiofrequency ablation of ventricular tachycardia in cardiomyopathy is frequently unsuccessful because of hemodynamic instability, multiple foci and recurrences. The Biosense CARTO nonfluoroscopic mapping and navigation system, when used to locate the area of the scar or reentry circuit, has the potential to improve the successful ablation, and reduce the rate of recurrence. We report 2 cases here of ventricular tachycardia in cardiomyopathy in which Biosense mapping was useful to identify the area of scar in 1 case, and the area of microreentry circuits in another. Radiofrequency ablation was possible and successful, while the use of conventional mapping was impossible or had recurrence. PMID- 11194017 TI - Myocardial injury after radiofrequency catheter ablation. AB - Radiofrequency catheter ablation has been a good treatment option for various types of cardiac arrhythmia. However there is concern about myocardial injury associated with radiofrequency catheter ablation. We studied myocardial injury with biochemical markers and echocardiogram in 41 consecutive patients who underwent electrophysiology study (EP study) and radiofrequency catheter ablation (RFCA) at our institute from April to July 2000. The concentration of biochemical markers (CK-MB mass, troponin T and myoglobin) and result of the echocardiograms were analyzed with other characteristics. In 41 patients subjected to EP study with possible RFCA, abnormal levels of troponin T, CK-MB mass and myoglobin were found in 46 per cent, 15 per cent and 44 per cent immediately after procedure, which went up to 64 per cent, 22 per cent and 2 per cent at twenty four hours. Compare to the group with normal troponin T level, the patients with abnormal level at 24 hours after RFCA had a longer procedure time (119+/-44 min. vs 90+/ 22 min.), more frequent use of impedance ablation catheters (65% vs 27%), more RF applications (9+/-8 vs 18+/-16) and more ventricular ablation sites (69% vs 9%). The echocardiogram results showed no remarkable abnormality in any patients. Troponin T was the most sensitive marker to detect thermal myocardial injury associated with radiofrequency catheter ablation. Prolonged procedure time, RF applications, the use of impedance ablation catheter and ventricular ablation site were associated with elevated troponin T concentration after RFCA. PMID- 11194018 TI - The prevalence of left ventricular hypertrophy and associated factors in a Thai population. AB - Electrocardiographic left ventricular hypertrophy (LVH) has been a bad prognostic factor for cardiovascular morbidity and mortality. However the prevalence and prognostic value of LVH are varied among nationalities and populations. Several factors have been shown to associate with LVH. Some factors are treatable such as hypertension. We prospectively studied the prevalence of LVH and associated factors in selected group of Thai population. The study population was 1,606 Shinawatra employees who were 30 year old or more. The prevalence of LVH was 13 per cent (210) among study population. Hypertension, lower body weight and male sex were significantly associated factors. In the subjects with LVH, the prevalence of hypertension was 25.6 per cent, male ratio was 5:1 and mean body weight was 57.7 kg, compare to 9.8 per cent prevalence of hypertension, 2:1 female ratio and mean body weight was 62.3 kg in the group without LVH. PMID- 11194019 TI - Radiofrequency catheter ablation: 5 years experience at Siriraj Hospital. AB - Between February 1995 to May 2000, 626 consecutive patients underwent radiofrequency catheter ablation for various types of cardiac arrhythmia. The mean age was 41 years, range 1-85 years. Mapping and ablation were guided by intracardiac electrogram and anatomical approaches. The initial success, compliction, recurrent and final success rates are shown below:- [table; see text] Conclusion, RFCA is an effective treatment and should be considered as first line treatment for certain tachyarrhythmia. PMID- 11194020 TI - Obesity and risk factors of coronary heart disease in healthy Thais: a cross sectional study. AB - Association between obesity and conventional risk factors for coronary artery disease is well established. Obesity is currently considered an independent risk for coronary artery disease. The relationship between body mass index (BMI) and fasting plasma lipids and glucose and blood pressures in non-obese subjects is not established. The authors studied relationships between BMI and lipids, and glucose, and blood pressure levels in healthy a population. The authors measured the weights and heights of 3,615 employees of a company during a routine yearly health examination. There were 1,250 males aged 31.3 +/- 6.6 and 2,365 females aged 29.3 +/- 4.9 years old. The average BMI for males and females were 23.5 +/- 3.6 and 20.1 +/- 3.0 respectively. The levels of total cholesterol (Chol), LDL cholesterol, and triglyceride (TG), fasting plasma glucose (FPG) had a positive relationship with BMI (r = 0.22, 0.26, 0.41, 0.20; p < 0.001). HLD-cholesterol had a negative correlation with BMI (r = -0.36, p < 0.001). Both systolic (SBP) and diastolic (DBP) blood pressures had a positive correlation with BMI. The association persisted after all values were adjusted by age and sex. BMI has a significant positive relationship with the conventional risk factors for coronary artery disease and a negative relationship with HDL-cholesterol. PMID- 11194021 TI - Utility of intraoperative transesophageal echocardiogram in congenital heart disease. AB - Intraoperative transesophageal echocardiogram (TEE) has improved the perioperative outcome in adult patients. The purpose of the current study was to assess the benefit of intraoperative TEE in patients with congenital heart disease undergoing surgical correction (repair). The results of the patients who had consecutively undergone intraoperative TEE during their congenital heart surgery between January 1998 to June 2000 were reviewed. There were 104 patients (whose ages ranged from one week old to 50 years old (median 5 years old) and their weights from 3 kg to 79 kg (median 15 kg). A significant impact was said to have occurred if these findings prompted a change in surgical procedure following a prebypass study or rebypass for repair of a residual defect. Prebypass TEE had a significant impact in seven patients (6.7%). TEE could be used as a guide to help repair in three patients. The postbypass TEE examination had a significant impact in 15 patients (14.4%). Of these 15 patients, eight were detected primarily by TEE examination. The group of patients in whom TEE had the most significant impact was in patients who had surgery related to the repair of the atrioventricular valve (complete or partial atrioventricular (AV) canal repair, Ebstein's anomaly; 9 out of 22 patients; 41%). A less significant impact was found in surgery for other complex congenital defects (single ventricle or complete transposition of great arteries; eight out of 46 patients; 17.4%). TEE had limited impact in simple congenital lesion. Intraoperative TEE is valuable in the perioperative care of patients with congenital heart defects. We found the most benefit in patients with complete or partial AV canal and Ebstein's anomaly. PMID- 11194022 TI - Screening for a D9N common mutation in exon 2 of the LPL gene in Thai normolipidemic and hyperlipidemic subjects. AB - Lipoprotein lipase (LPL) is a multifunctional protein, playing a major role in the hydrolysis of triglyceride-rich lipoproteins. It also affects the maturation of high density lipoprotein (HDL) and low density lipoprotein (LDL). A D9N substitution is a frequent mutation found in exon 2 of the LPL gene. It is due to a G --> A transition causing a substitution of Asp by Asn at amino acid residue 9 of the protein. This mutation was screened for in 94 Thai primary dyslipidemic (46 hypercholesterolemic and 48 combined hyperlipidemic) subjects compared to 32 normal healthy subjects using PCR-RFLP. Such a mutation has not, yet, been detected in any of these Thai subjects. PMID- 11194023 TI - Analytical and clinical performance of two homogeneous assays for measuring of LDL-cholesterol. AB - A clinical laboratory currently estimates LDL-Cholesterol (LDL-C) concentration using the Friedewald calculation, which requires fasting specimens and is subject to error with increasing triglycerides levels. We evaluated the analytical and clinical performance of the direct LDL-C assay from two companies, Roche Diagnostics (LDL-C(Roche)) and Wako Pure Chemical (LDL-C(Wako)). Both methods meet current guidelines for precision with within-run coefficients of variation less than 3 per cent. The LDL-C(Roche) assay correlated well with the LDL-C from the Friedewald equation (LDL-C(Fried), r = 0.958, y = 0.85x + 17.08 mg/dL, n = 422). The LDL-C(Wako) assay also correlated with the LDL-C(Fried) (r = 0.946, y = 0.86x + 7.81 mg/dL, n = 422). In addition, at the medical decision cutoff points, LDL-C(Roche) assay and LDL-C(Wako) showed positive predictive values of 87.44 per cent and 69.67 per cent respectively. We conclude that the LDL-C(Roche) assay meets the currently established analytical and clinical performance, but LDL C(Wako) assay meets only analytical performance. Clinical performance needs further evaluation. PMID- 11194024 TI - Serum cardiac troponin T in unstable angina pectoris patients. AB - Cardiac troponin T (cTnT) is a regulatory contractile protein not normally found in blood. Its detection in the circulation has been shown to be a sensitive and specific marker for myocardial cell damage. In this study, we used a second generation enzyme immunoassay for cTnT to determine whether its presence in the serum of patients with unstable angina was a prognostic indicator. Thirty patients with unstable angina pectoris (UAP) and 30 patients with Q-wave acute myocardial infarction (AMI) were screened for serum CK-MB activity and cTnT at 6, 12, 24 and 48 hours after the onset of chest pain, All of the mean concentrations of CK-MB activity determined in UAP patients were less than the upper limit of normal (25 U/L). Meanwhile, the mean concentration of cTnT at 6, 12, 24 and 48 hours after onset of chest pain were higher than the cutoff values (0.1 microg/L), We found that one third of UAP patients had serum cTnT at the time of admission more than 0.1 microg/L and that these groups of patients were associated with a high risk for cardiac events. Our results suggested that patients with elevated serum cTnT could be considered as high-risk patients for developing myocardial infarction, Patients with normal cTnT levels and a low or intermediate clinical risk could be stabilized and further stratified noninvasively. PMID- 11194025 TI - Screening for mutations in exon 4 of the LDL receptor gene in Thai subjects with primary hypercholesterolemia: detection of a novel mutation D151Y by PCR-CFLP. AB - A mutation in low density lipoprotein (LDL) receptor gene causes an autosomal codominant disorder namely familial hypercholesterolemia (FH). Mutations in the LDL receptor gene are very heterogeneous at the DNA levels, occurring in all 18 exons of the gene. However, exon 4 has been found to be the hot spot for mutational events. In this study DNA from 45 Thai subjects with primary hypercholesterolemia was screened for mutations in the hot spot exon 4. The DNA samples were amplified by Polymerase Chain Reaction (PCR) and screened for mutation by Cleavase Fragment Length Polymorphism (CFLP) technique. Identification of mutation was performed by direct sequencing of PCR product. From this screening, one female patient was found to be heterozygous for a novel mutation which was due to a G to T transversion at nucleotide 514. This transversion would change the species-conserved amino acid at codon 151 from charged R group aspatic (GAC) to uncharged R group tyrosine (TAC), termed D151Y. From the same screening strategy, we found that this mutation was absent in 33 healthy normolipidemic subjects. In this index subject, Arg 3500 Gln mutation in apo B-100 gene, causing hypercholesterolemia namely familial defective apo B-100 (FDB), was not found. Therefore, hypercholesterolemia in this index subject was possibly caused by the D151Y mutation in the LDL receptor gene. PMID- 11194026 TI - Effect of Ava II and NcoI polymorphisms at the low density lipoprotein receptor gene on plasma lipid levels in a group of Thai subjects. AB - The contribution of common genetic variations at the LDL receptor gene in determining interindividual differences in plasma lipid levels in the general population has been observed in several studies. In this study, we employed the PCR-RFLP method to investigate such an effect of the common Ava II (exon 13) and Nco I (exon 18) polymorphisms at the low density lipoprotein (LDL) receptor gene locus in 54 normolipidemic Thai subjects. The mean LDL-C level was slightly higher in the Ava II (+/+) genotype than the other Ava II genotypes. This difference was significant at the 5 per cent level although there were only three homozygotes with Ava II (+/+) genotype. The average effect of Ava II (+) allele was to increase LDL-C level by 6.75 mg/dl. A gene-dosage effect was not observed for this polymorphism. In addition, the subjects with Ava II (+/+) genotype also tended to have high serum total cholesterol and triglyceride and low HDL-C levels. Nco I polymorphism revealed no statistically significant effect on lipid levels in these subjects. However, the subjects with (+) allele tended to have high levels of LDL-C, serum total cholesterol and triglyceride. PMID- 11194027 TI - Mutation analysis of exon 9 of the LDL receptor gene in Thai subjects with primary hypercholesterolemia. AB - The low density lipoprotein (LDL) receptor plays an important role in cholesterol homeostasis. A mutation in this gene causes an autosomal codominant disorder, namely familial hypercholesterolemia (FH). In this study, single strand conformation polymorphism (SSCP) analysis was used to screen for mutations in exon 9 of the LDL receptor gene in a group of 45 Thai patients (11 males and 34 females) with primary hypercholesterolemia. The peptide encoded by exon 9 belongs to the epidermal growth factor (EGF) precursor homology domain which is highly conserved in the LDL receptor protein. An abnormal SSCP pattern was observed in one female patient. The same screening strategy was also used to screen DNA samples from 33 normolipidemic subjects. All of these samples showed normal SSCP pattern. By direct DNA sequencing, the underlying mutation in the DNA with abnormal SSCP pattern was identified. The index subject was heterozygous for a T to C transition at nucleotide 1235. This transition would cause a nonconservative substitution of a nonpolar side chain amino acid "methionine" at codon 391, with an uncharged polar side chain amino acid "threonine", note M391T. From multiple amino acid sequence alignment in six species, the amino acid at codon 391 and the others nearby are completely conserved. Such nonconservative substitution of an amino acid residue in a highly conserved region could consequently result in a functional and/or structural defect in the receptor protein. In conclusion, we propose that M391T is likely to be the cause of hypercholesterolemia in this index subject. PMID- 11194028 TI - Coarctation of the aorta in children at Siriraj Hospital. AB - A retrospective analysis of 33 children who were diagnosed to have coarctation of aorta at Siriraj Hospital between January 1989 and December 1998 was undertaken. There were 21 males (64%) and 12 females (36%). Their ages ranged from one day to 11 years (median 2 months). The majority of the patients (78.8%) were presented early within the first year of life. The predominant clinical manifestations were congestive heart failure (69.6%), systemic hypertension of the upper extremities (36.3%) and decreased femoral pulses. Chest roentgenogram revealed cardiomegaly (70%) and increased pulmonary blood flow (84%), reflecting congestive heart failure and associated left-to-right shunting. Electrocardiogram showed normal pattern (33.3%), right ventricular hypertrophy (33.3%), left ventricular hypertrophy (22.2%) and biventricular hypertrophy (11.2%). The younger the patient is, the more right ventricular predominance is demonstrated. According to the echocardiogram and/or aortogram, juxtaductal type was found in 51.5 per cent, postductal type in 27.3 per cent and preductal type in 21.2 per cent. Medical management included prostaglandin E1 infusion in a newborn baby presented with low-cardiac output state, anticongestion and antihypertension, if indicated, followed by surgical correction. The result of coarctectomy with end-to-end anastomosis with or without arch augmentation was good. The operative mortality rate was 5 per cent. The overall mortality in the present study was 9 per cent. The most common causes of death were multiorgan failure and pulmonary infection. Residual coarctation was found in 5 per cent. PMID- 11194029 TI - A 5-year prospective study of conventional risk factors of coronary artery disease in Shinawatra employees: a preliminary prevalence survey of 3,615 employees. AB - We conducted a prevalence survey of conventional risk factors of coronary artery disease in 3,615 Shinawatra employees and we planned to prospectively follow up this population to determine the impact of the risk factors in the development of coronary disease. The prevalence of hypertension, diabetes mellitus, hyperlipidemia, obesity, physical inactivity and smoking were 7.4 per cent, 1.4 per cent, 21.1 per cent, 13.9 per cent, 76.3 per cent and 16.3 per cent respectively. The awareness of hypertension, diabetes mellitus and hyperlipidemia were 42.2 per cent, 78 per cent and 32.9 per cent respectively. The prevalence of the risk factors was more common in males and increased with increasing age. Dependent variables which were associated with hypertension included: excessive weight; male sex; increasing age; hypercholesterolemia and diabetes mellitus. Variables which were associated with diabetes mellitus were hypertriglyceridemia, hypertension, male sex, increasing age and excessive weight.. Variables which were associated with hypercholesterolemia were hypertriglyceridemia, high HDL cholesterol, increasing age, excessive weight and hematocrit level while overweight, hypercholesterolemia, low HDL-cholesterol, smoking, hematocrit level, low income and increasing age were associated with hypertriglyceridemia. Excessive weight was associated with hypertriglyceridemia, low HDL-Cholesterol, presence of hypertension, hypercholesterolemia, diabetes mellitus, increasing age and low education. PMID- 11194030 TI - Cell-mediated and humoral immunity and phagocytic ability in chicken Lines divergently selected for serum immunoglobulin M and G levels. AB - Humoral and cell-mediated immunities and phagocytic ability were examined at the third and fourth generations of selection in two pairs of chicken lines (at 10 wk of age) that were divergently selected for levels of high serum Ig M (HIM), low serum Ig M (LIM), high serum Ig G (HIG), and low serum Ig G (LIG). Cell-mediated immunity was examined by splenomegaly assay at 12 wk of age. At 20 and 23 wk of age, 20 birds from the respective lines were injected Brucella abortus (BA), and blood samples were collected at 7 and 14 d postprimary immunization (PPI) and postsecondary immunization (PSI). Phagocytic ability was measured by carbon clearance assay at 25 and 30 wk of age. The results showed that the LIG line had higher degree of splenomegaly indices than the HIG line in both generations. The HIM and HIG lines had significantly (P < 0.05) higher total antibody titers to BA than their low counterparts. Similarly, mercaptoethanol-resistant (MER) antibody titers to BA, as measured only in the fourth generation, were significantly (P < 0.05) higher in the HIM and HIG lines than their low counterparts. In both generations, the HIM and HIG lines had significantly (P < 0.01) faster carbon clearance ability than the LIM and LIG lines. The results suggest that both pairs of selected lines exhibited divergence in immunocompetence, although they had been selected for serum Ig isotypes. PMID- 11194031 TI - Developmental instability in japanese quail genetically selected for contrasting adrenocortical responsiveness. AB - Differences in developmental instability were assessed with Japanese quail of two lines that had been genetically selected over several generations for reduced (low stress, LS) or exaggerated (high stress, HS) plasma corticosterone response to brief mechanical restraint. At 32 wk of age, three bilateral traits were selected for study in each quail line. The characteristics chosen were length of the metatarsus (shank length, SHL), diameter of the shank (SHD) perpendicular to the spur, and distance between the auditory canal and the nares (face length, FL). Significantly greater bilateral trait size variances were associated with the measurement of SHL (P < 0.0088) and FL (P < 0.0016) in the HS line than in the LS line. SHD variances did not differ (P = 0.22) in quail of the HS and LS lines. These findings suggest that developmental instability (i.e., fluctuating asymmetry, FA) is more pronounced in HS quail than in LS quail. Previous studies have shown that not only do quail of the HS line show greater adrenocortical responsiveness to a wide range of stressors but that they are also more easily frightened than LS birds. Therefore, the line differences in FA found here may reflect the birds' differential responsiveness to chronic social and physical environmental stressors. The present findings also support previous suggestions that measuring asymmetries in bilateral traits could be an additional and valid method of assessing stress and of comparing phenotypic stability in selected populations. PMID- 11194032 TI - A model for persistency of egg production. AB - The objectives of our study were to propose a new definition for persistency of egg production and to develop a mathematical model to describe the egg production curve, one that includes a new measure for persistency, based on the proposed definition, for use as a selection criterion to improve total egg production. Persistency of egg production is an important determining factor for total egg production. Hens with the same total production, however, can exhibit different egg production curves because of differences in persistency. We propose a new definition for persistency of egg production: the number of weeks during which a level of constant production is maintained. No egg production model exists that includes a measure of persistency in terms of duration of time or that allows this measure of persistency to be derived from model parameters. It was necessary, therefore, to develop a new model to describe an egg production curve for a flock: equation [see text] and for an individual: equation [see text] where y(t) = egg production at time t, t1 and t2 = times at transition, r = duration of transition, y(p) = level of constant production, b4 = rate of decline in production, and P = persistency of constant production. These parameters measure directly the important biological characteristics of an egg production curve. To illustrate the model, six data sets were used: two from flocks (one pullet flock and one hen flock) and four from two pairs of individuals. The proposed definition of persistency should be important for genetic selection because it might be desirable to select for increased persistency. The novel approach to the definition and measure of persistency presented here should provide a better understanding of the relationship between the new measure of persistency and other characteristics of egg production. PMID- 11194033 TI - The effect of storage and strain of hen on egg quality. AB - Eggs from 31-wk-old ISA-White and ISA-Brown hens were sampled immediately after lay and after periods of storage of 1, 3, 5, and 10 d at room temperature. Longer periods of storage resulted in lower albumen weight and albumen height and higher albumen pH. Eggs from ISA-Brown hens had more albumen and shell than those from ISA-White hens, likely due to differences in selection history rather than due to pleiotropic effects of eggshell color. Within each line and storage period, the egg weight was more closely associated with albumen weight than with yolk or shell weight. The albumen height of eggs from ISA-Brown hens was lower than that of ISA-White hens at all storage times, but the albumen pH was not affected by the strain. Albumen height and albumen pH were statistically unrelated in fresh eggs, but the association became larger as the storage period increased, suggesting that albumen height measures factors that are present when the egg is laid and changes during storage, whereas albumen pH measures only the effect of storage. PMID- 11194034 TI - Infection and immunity in broiler chicken breeders vaccinated with a temperature sensitive mutant of Mycoplasma gallisepticum and impact on performance of offspring. AB - A comparison of infection and immunity to Mycoplasma gallisepticum (MG) in broiler chicken breeders vaccinated with a temperature-sensitive mutant of MG versus nonvaccinated chickens, and the impact on the performance of their offspring was conducted. Infection and immunity in breeders were assessed by culture and enzyme-linked immunoassay, respectively. However, performance in their offspring was assessed by studying MG infection in embryos, occurrence of infection titers to MG in relation to mortality, and feed conversion in the broilers. Five out of 10 broiler chicken breeder flocks raised on the same multiple-age farm with a long history of mycoplasmosis were vaccinated intraocularly once with a temperature-sensitive MG mutant vaccine (ts-11) at an average age of 7.5 wk; another five breeder flocks were left as unvaccinated controls exposed to field MG. The average recoveries of ts-11 organisms from tracheas and infraorbital sinuses of 41-wk-old vaccinates were 88 and 84%, respectively. No field MG organisms were recovered from vaccinates between 15 and 41 wk of age. The recovery of field MG organisms from tracheas and sinuses of nonvaccinated chickens increased to an average of 100% at 41 wk of age. A significant decrease (P < 0.05) in the average percentage of MG-seroconverted breeders occurred in ts-11-vaccinated flocks in comparison with nonvaccinated, MG infected flocks at 15, 20, 23, 29, 32, 36, and 41 wk of age. The average infection prevalence by MG in the vitelline membrane of 7-d-old embryos produced by the five unvaccinated breeder flocks peaked at 79% when their respective hatching eggs were collected at 36 wk of breeder's age. Embryos of ts-11 vaccinated flocks had zero prevalence of MG infection at all times between 29 and 57 wk of breeder's age. Seroconversion to MG (average of 17.7%) at 42 d of age was only present in sera of 10 offspring broiler flocks of the nonvaccinated breeders. However, a lack of seroconversion to MG occurred in 10, 42-d-old offspring broiler flocks of the five ts-11-vaccinated breeder flocks. This lack was associated with a lower, better average feed-conversion ratio (2.05) (P < 0.05) and a lower average mortality percentage (5.3%) (P < 0.05) in comparison with those obtained in the offspring of the five unvaccinated, MG-infected breeder flocks. The results indicate that vaccination of broiler chicken breeders with a temperature-sensitive mutant of MG prevented infection by field MG in tracheas and infraorbital sinuses of these breeders and in the vitelline membranes of their embryos. In addition, the broiler offspring of the vaccinated breeders had a better production performance. PMID- 11194035 TI - Allelic complementation between MHC haplotypes B(Q) and B17 increases regression of Rous sarcomas. AB - Major histocompatibility (B) complex haplotypes B(Q) and B17 were examined for their effect on Rous sarcoma outcome. Pedigree matings of B(Q)B17 chickens from the second backcross generation (BC2) of Line UCD 001 (B(Q)B(Q)) mated to Line UCD 003 (B17B17) produced progeny with genotypes B(Q)B(Q), B(Q)B17, and B17B17. Six-week-old chickens were injected with subgroup A Rous sarcoma virus (RSV). The tumors were scored for size at 2, 3, 4, 6, 8, and 10 weeks postinoculation. A tumor profile index (TPI) was assigned to each bird based on the six tumor scores. Two experiments with two trials each were conducted. In Experiment 1, chickens (n = 84) were inoculated with 30 pock-forming units (pfu) RSV. There was no significant B genotype effect on tumor growth over time or TPI among the 70 chickens that developed tumors. Chickens (n = 141) were injected with 15 PFU RSV in Experiment 2. The B genotype significantly affected tumor growth pattern over time in the 79 chickens with sarcomas. The B(Q)B17 chickens had the lowest TPI, which was significantly different from B17B17 but not B(Q)B(Q). The data indicate complementation because more tumor regression occurs in the B(Q)B17 heterozygote than in either B(Q)B(Q) or B17B17 genotypes at a 15 pfu RSV dose and significantly so compared to B17B17. By contrast, the 30 pfu RSV dose utilized in the first experiment overwhelmed all genotypic combinations of the B(Q) and B17 haplotypes, suggesting that certain MHC genotypes affect the immune response under modest levels of viral challenge. PMID- 11194036 TI - Dietary polyunsaturated fatty acids alter lymphocyte subset proportion and proliferation, serum immunoglobulin G concentration, and immune tissue development in chicks. AB - The effects of fat source on immune response of the offspring of the Single Comb White Leghorn laying hens were investigated. The laying hens were fed for 6 wk with a wheat-soybean meal basal diet with added sunflower oil (SO), animal oil (AO), linseed oil (LO), or menhaden fish oil (FO) at 5% (wt/wt). Upon hatching, the chicks (30/group) were given the same types of diets for 8 wk. The dietary SO, AO, and LO provided different n-6 to n-3 polyunsaturated fatty acids (PUFA) ratios. The FO and LO had ratios of n-6 to n-3 PUFA that were close but had different components of n-3 PUFA. The results demonstrated that the chicks fed LO or FO had significantly lower (P < 0.05) splenocyte proliferative response to ConA than the chicks fed SO or AO at either 4 wk or 8 wk of age, with a stronger (P < 0.05) suppressive effect produced by LO at 4 wk. A significantly lower (P < 0.05) splenocyte response to PWM was produced by the chicks fed AO, LO, and FO compared with the chicks fed SO at 8 wk. The thymus lymphocyte proliferation in response to ConA at 4 wk was lower (P < 0.05) in the chicks fed AO, LO, and FO than in the chicks fed SO. Both LO and FO elevated (P < 0.05) the proportion of IgM+ lymphocytes in spleen, but only FO increased (P < 0.05) the serum IgG concentration. The LO elevated (P < 0.05) the percentage of CD8+ T-lymphocytes but not the ratio of CD4+ to CD8+ cells (P > 0.05) in spleen. Growths of thymus, spleen, and bursa were impacted significantly (P < 0.05) by the amount of dietary PUFA, the ratio of n-6 to n-3 fatty acids, and n-3 PUFA components. PMID- 11194037 TI - Effects of dietary conjugated linoleic acid and linoleic:linolenic acid ratio on polyunsaturated fatty acid status in laying hens. AB - A study was conducted to determine the effects of dietary conjugated linoleic acid (CLA) and the ratio of linoleic:linolenic acid on long-chain polyunsaturated fatty acid status. Thirty-two 31-wk-old White Leghorn hens were randomly assigned to four diets containing 8.2% soy oil, 4.1% soy oil + 2.5% CLA (4.1% CLA source), 4.1% flax oil + 2.5% CLA, or 4.1% soy oil + 4.1% flax oil. Hens were fed the diets for 3 wk before eggs and tissues were collected for the study. Lipids were extracted from egg yolk and tissues, classes of egg yolk lipids were separated, and fatty acid concentrations of total lipids, triglyceride, phosphatidylethanolamine, and phosphatidylcholine were analyzed by gas chromatography. The concentrations of monounsaturated fatty acids and non-CLA polyunsaturated fatty acids were reduced after CLA feeding. The amount of arachidonic acid was decreased after CLA feeding in linoleic acid- and linolenic acid-rich diets, but amounts of eicosapentaenoic acid and docosahexaenoic acid were increased in the linolenic-rich diet, indicating that the synthesis or deposition of long-chain n-3 fatty acids was accelerated after CLA feeding. The increased docosahexaenoic acid and eicosapentaenoic acid contents in lipid may be compensation for the decreased arachidonic acid content. Dietary supplementation of linoleic acid increased n-6 fatty acid levels in lipids, whereas linolenic acid increased n-3 fatty acid levels. Results also suggest that CLA might not be elongated to synthesize long-chain fatty acids in significant amounts. The effect of CLA in reducing the level of n-6 fatty acids and promoting the level of n-3 fatty acids could be related to the biological effects of CLA. PMID- 11194038 TI - Prediction of the effect of enzymes on chick performance when added to cereal based diets: use of a modified log-linear model. AB - A previous study demonstrated that a log equation could be used to predict the relationship between the amount of a crude enzyme added to a diet and chick performance. The objective of the current study was to determine if a modification of the original equation, in conjunction with a computer program, would overcome some of its limitations. The modified equation was Y = A + B log (CX + 1), where Y is the estimated performance value; A is the intercept that represents the performance without enzyme supplementation; B, the slope of the equation (performance change per log unit of an enzyme in the diet), is a measure of an enzyme efficacy; C is an amplified factor; and X is the amount of enzyme in the diet. The results demonstrated that the new model more accurately predicted chick performance than that of the original equation with correlations (r) between chick performance and amount of different enzymes added to the diet ranging from r = 0.80 to 0.99 (P < 0.05). In addition, the same trends were found when the model was used to assess the efficacy of a given enzyme added to corn-, wheat-, barley-, and rye-based diets or for combinations of two dietary components (rye and wheat). The model proposed in this study provides a new means of assessing the overall efficacy of an enzyme preparation. This model could be routinely used by enzyme and livestock producers to establish the best combination of different cereals and enzymes so as to maximize net returns. PMID- 11194039 TI - The effects of enzyme addition to broiler diets containing high concentrations of canola or sunflower meal. AB - The effects of two commercial enzyme products on the nutritive value of canola meal (CM) and sunflower meal (SFM) were determined in a classical AME bioassay with special emphasis on the utilization of nonstarch polysaccharides (NSP). The enzymes were added to semi-purified broiler grower diets based on corn and casein containing 35% CM or 35% SFM, respectively. Feed intake, growth, and AME of the diets were significantly (P < 0.001) affected by type of oilseed meal included in the diet. Birds fed the SFM-based diets had a significantly (P < 0.001) higher growth rate and AME and a lower feed conversion ratio (FCR) than did birds fed the CM-based diets. The addition of enzymes to either CM- or SFM-based diets had no significant effects on growth performance and AME; however, the addition of enzymes to CM-based diets resulted in a significant reduction in the concentration of soluble NSP in the jejunum (Enzyme A) or a significant reduction of total NSP in the jejunum (Enzyme B). The AMEn was significantly lower in diets containing CM supplemented with Enzyme B. The addition of enzymes to SFM-based diets significantly improved NSP digestion in the jejunum and protein digestion in the ileum. The results of this study indicate that commercial enzyme products had some effects in diets containing high concentrations of CM or SFM. However, these effects could only be seen after detailed analyses of feed and digesta and did not result in significant improvement in growth performance of broilers. PMID- 11194040 TI - Effect of pressure processing on amino acid digestibility of meat and bone meal for poultry. AB - In the future, it may become desirable or required to process meat and bone meal (MBM) under pressure to reduce human health concerns associated with bovine spongiform encephalopathy (BSE). Therefore, three experiments evaluated the effects of different processing pressures on the digestibility of amino acids (AA) in MBM when the pressure processing was done after typical rendering (Experiments 1 and 2) or during the initial rendering process of raw materials (Experiment 3). Processing pressures varied from 0 to 60 psi in experimental or commercial feather meal cookers. Increasing pressure during processing reduced MBM Cys concentrations in Experiments 1 and 2. True digestibilities of most AA were significantly decreased by increasing pressures in Experiments 1 and 2, and reductions were generally largest for Cys and Lys, particularly Cys, and increased with severity as pressure increased. For example, in Experiment 1, Cys digestibility decreased from 65 to 50 to 15%, and Lys digestibility decreased from 76 to 68 to 41% as the MBM was processed at 0, 30, and 60 psi, respectively, for 20 min. When the pressure processing occurred during the initial rendering of the MBM raw material (Experiment 3), a significant reduction in digestibility of most AA was observed only at 60 psi, and the decrease was much less than that observed in Experiments 1 and 2. Our results indicate that pressure processing of MBM decreases the digestibility of AA for poultry. Thus, pressure processing of MBM to reduce potential BSE infectivity will likely decrease the nutritional value of the MBM. PMID- 11194041 TI - Isoleucine imbalance using selected mixtures of imbalancing amino acids in diets of the broiler chick. AB - Three experiments were conducted to determine the isoleucine requirement of a broiler from the time of hatch to 16 d of age. Chicks in the experiments were fed an isoleucine-limiting diet composed of wheat and peanut meal as the primary protein sources; this diet was used to investigate various mixtures of amino acids as imbalancing agents for isoleucine. The isoleucine requirement for maximum weight gain and feed efficiency was determined on the basis of broken line regression analysis to be 0.63 to 0.65% of the diet or 3.28 to 3.38% of dietary protein. A similar diet, marginally limiting in isoleucine, was used to investigate the response of chicks to the addition of various mixtures of amino acids to the diet. Chicks that received a 5% dietary addition of 11 amino acids consisting of equimolar concentrations of leucine, valine, histidine, methionine, phenylalanine, tryptophan, tyrosine, alanine, glycine, serine, and threonine had significantly lower weight gain and feed consumption and a higher feed conversion ratio than did chicks fed the basal diet. These adverse effects were only partly prevented by an isoleucine supplement. The large neutral amino acids, histidine, methionine, phenylalanine, tryptophan, and tyrosine, accounted for most of the effect of the mixture. No effect of a mixture of leucine and valine or a mixture of the small neutral amino acids (alanine, glycine, serine, and threonine) at the same concentrations as those in the mixture of the 11 amino acids was observed. Lysine and arginine were the only two indispensable amino acids not present in the mixture of 11 amino acids. A subsequent experiment demonstrated that these amino acids did not become co-limiting with isoleucine when the diet was imbalanced with the amino acid mixture. These results indicate that an isoleucine imbalance in chicks is readily precipitated by excessive dietary concentrations of large neutral amino acids in diets that are otherwise marginally adequate in isoleucine. PMID- 11194042 TI - Effect of dietary protein intake during the pullet-to-breeder transition period on early egg weight and production in broiler breeders. AB - The effects of CP intake on broiler breeder hen performance were evaluated. A flock of pullets was reared in floor pens from 0 d to 20 wk of age. At 20 wk of age, 96 pullets were randomly assigned to one of three feeding regimens with 14, 16, or 18% dietary CP. Daily feed allocation from 20 to 29 wk of age was identical for all three treatments and was based on the BW of the birds fed the 16% CP diet. Photostimulation occurred at 22 wk of age. At 29 wk of age, the hens were killed for determination of carcass characteristics. Dietary protein intake did not influence BW or BW gain throughout the trial. There were no differences in age at sexual maturity among treatments. From 25 to 28 wk of age, the hens on the 16 and 18% CP treatments had a significantly greater egg weight than did hens in the 14% CP group. The 14% CP treatment was unable to sustain as high a level of egg production as the other two treatments at 29 wk of age. The number of settable eggs was also lowest for the 14% CP treatment. The CP level in the diet did not affect the weights of the Pectoralis major or minor. Carcass composition was also not different among the treatments. Increased levels of CP in the prelay and early lay diets increased egg size and production rate although had minimal effect on carcass and ovarian parameters. PMID- 11194043 TI - Efficacy of sperm mobility assessment in commercial flocks and the relationships of sperm mobility and insemination dose with fertility in turkeys. AB - Our objectives were to evaluate: 1) the efficacy of the Sperm Mobility Test on commercial turkey farms, and 2) the influence of sperm mobility phenotype on fertility when insemination parameters are varied. In research flocks, differences in sperm mobility among toms are predictive of fertility. We wanted to test the efficacy of this sire selection test in practical, real-world situations, evaluating its usefulness in terms of assessing large numbers of toms, different strains of turkeys, and variable management practices. Utilizing field study results, controlled studies were then conducted to improve test parameters. For the field trials, semen from each of 405 breeder toms (11 strains or lines) was evaluated either in duplicate (n = 285) or in triplicate (n = 120). Sperm mobility was normally distributed among all toms tested, except for one strain. Because the sperm mobility indices for toms evaluated in these field trials were higher than those observed in research flocks, the Sperm Mobility Test was modified to increase the separation between high and low sperm mobility phenotypes by increasing the concentration of Accudenz. To determine the effects of sperm mobility and insemination dose on sustained fertility through time, hens from a research flock were inseminated twice before the onset of lay with sperm from toms classified as high-, average-, or low-mobility in concentrations of 25 to 400 million sperm per artificial insemination dose, and egg fertility was evaluated over a 5-wk period. Toms with the high-mobility sperm phenotype maintained higher fertility (P < 0.05) over the 5-wk period at all insemination doses compared with toms with low-mobility sperm. Toms with high-mobility sperm sired equal numbers of poults in a sperm competition study in which numbers favored low-mobility toms by 3:1. These results demonstrate that the Sperm Mobility Test can be used for on-farm evaluation of semen quality of toms in commercial flocks and that sperm mobility influences fertility and sire fitness. PMID- 11194044 TI - The effects of methylxanthines on the mobility of stored turkey sperm. AB - The mobility of pooled turkey sperm following various storage regimens was assessed by objectively measuring the ability of sperm to penetrate a 2% Accudenz [5-(N-2,3-dihydroxypropylacetamido)-2,4,6-tri-iodo-N,N'-bis(2,3 dihydroxypropyl)isophthalamide] solution at 41 C. When semen was diluted with Beltsville poultry semen extender and stored at 5 C with agitation at 150 rpm, sperm mobility declined as the storage interval increased (P < or = 0.05), with mobility scores (mean +/- SEM) of 0.440+/-0.029, 0.374+/-0.031, 0.282+/-0.011, 0.202+/-0.019, and 0.130+/-0.019 for 0-, 3-, 6-, 24-, and 48-h storage, respectively. For a 10-wk fertility trial using the same storage method, sperm mobility and fertilizing capacity of semen were significantly reduced following 24-h storage compared with values for unstored semen. The sperm mobility scores were 0.404+/-0.051 and 0.101+/-0.046 for unstored and 24-h stored semen, respectively, whereas the percentage of fertilized eggs was 95.9+/-5.1 for unstored semen and 48.0+/-5.1 for 24-h stored semen. When caffeine or pentoxifylline was added to semen at 2.5, 5, or 10 mM, no significant effect on sperm mobility was seen, regardless of whether these compounds were added to unstored semen, were present during 6-h storage, or were added following the 6-h storage interval. These studies demonstrate that sperm mobility and fertilizing capacity of pooled turkey semen declines with storage, and that addition of caffeine or pentoxifylline either during or after storage does not affect sperm mobility. PMID- 11194045 TI - Paternal influences on turkey embryonic growth in the absence of changes in egg weight and eggshell conductance. AB - The hypothesis was proposed that embryonic growth could be influenced paternally in the absence of changes in egg weight or eggshell conductance. Sire families were established by selecting 11 sires based on blood sampling of approximately 50 commercial turkey males. Southern blot analysis was used to identify the most distantly related individuals in the subpopulation. Five hen siblings or half siblings of the males were randomly assigned to each male to randomize effects of egg size and eggshell conductance. Artificial inseminations were performed weekly for 17 wk, using each sire with the assigned hens. Fertilized eggs were collected and set in incubators at biweekly intervals. Offspring were observed at the time of hatching for sex, body weight, and blood glucose concentration. Significant differences among sires were observed at hatching for poult weights and blood glucose concentration, and a significant correlation between the BW and glucose concentration was noted. Progeny of sires with the highest and lowest BW and blood glucose concentrations were subsequently compared. Mean BW of poults from different sires differed by as much as 10 g, although they were hatched from eggs of the same weight. Elevated blood glucose was associated with heavier BW; heavier heart, liver, and muscle weights; a rapid utilization of glycogen at pipping; and increased gluconeogenesis as measured by plasma organic acids and glucose-6-phosphatase activity. We conclude that poult embryonic growth differs even when not mediated by egg size and functional characteristics. PMID- 11194046 TI - Correlation of body weight with hatchling blood glucose concentration and its relationship to embryonic survival. AB - The negative correlation between selection for rapid growth and embryonic survival was investigated. Embryonic growth was assessed with hatchling weights of a closed population of commercial turkey breeders. Hatchling weights were highly significantly (P < 0.0001) and positively correlated with blood glucose concentrations at hatching. This relationship existed for both tom and hen poults. Significant differences among dams for hatchling blood glucose were observed. Further experiments examined dams selected for producing poults hatching with high (High) or low (Low) blood glucose concentrations. The High embryos were in larger-sized eggs with the same eggshell conductance but with significantly lower conductance constants than the Low embryos, suggesting that Low had longer incubation periods. High embryos grew faster than Low embryos with elevated organ glycogen concentrations. Organic acid analysis indicated elevated plasma alpha-ketoglutarate, urate, and beta-hydroxy butyrate concentrations, suggesting a greater reliance on gluconeogenesis for the High group. Posthatch growth was significantly positively correlated with hatchling blood glucose concentrations in toms but not in hens. Tom poults hatching with elevated glucose were heavier than low glucose hatch mates until 22 wk of age, but hen poults displayed no differences until 16 wk when High hens weighed less than Low hens. These data suggest that the negative correlation between rapid growth and embryonic survival is related to egg-shell conductance constants and embryonic energy metabolism. PMID- 11194047 TI - Improvement of hatchability of chicken eggs injected by blastoderm cells. AB - In our first experiment, we studied the effect of injection method of blastoderm cells (BC) into the subgerminal cavity of White Leghorn embryos on hatchability of chicken chimeras. Freshly laid eggs were injected through a hole made in the equatorial plane of the eggshell (Method A). In Method B, eggs were stored pointed end down for 5 to 7 d prior to injection, and a hole was cut in the blunt end of the eggshell. An advantage of Method B was that the early embryonic mortality was reduced (P < or = 0.01) and resulted in higher hatchability (41.0%; 43/105) than Method A (9.8%; 14/143). In the second experiment, we studied chicken hatchabililty as influenced by windowing (no hole, Group 1; hole in the equatorial plane, Group 2; hole in the blunt end of egg, Groups 3 and 4) and egg turning (Groups 1 and 4) or not (Groups 2 and 3) during incubation. The hatchability percentages were as follows: 67.9 (Group 1) 0.0, (Group 2) 23.3, (Group 3), and 56.8 (Group 4). A statistically significant difference (P < or = 0.05) was noted between Group 1 or 4 and the other groups. We found no statistically significant differences in the weight changes (g) but did note certain differences in the egg weight loss (%) among different egg treatments. In the third experiment, we investigated the influence of origins of BC donors: Rhode Island Red (RIR), Barred Plymouth Rock (BPR), and Green-legged Partridgelike (GP) on hatchability of putative and somatic chimera chickens. The hatchability of chimeras was dependent on the adequate assortment of BC of the donor and ranged from 7.4% (RIR) to 56.1% (GP). In the case of BC injection of the GP breed, good hatchability was accompanied by very high percentage (86.9; 20/23) of somatic chimeras. PMID- 11194048 TI - Biliary glutathione secretion in male single comb white leghorn chickens after inhibition of gamma-glutamyl transpeptidase. AB - The amount of hepatic export of glutathione into bile and the importance of gamma glutamyl transpeptidase (gammaGT) activity for catabolizing glutathione in the bile duct, have not been reported previously for domestic fowl. Therefore, the primary objective of this study was to establish baseline values of biliary glutathione, and a secondary objective was to investigate the effect of acivicin (AT-125; a gammaGT inhibitor) on biliary glutathione in the chicken. Cannulae were placed in the carotid artery (to measure blood pressure) and into the left bile duct of anesthetized male Single Comb White Leghorn (SCWL) chickens (n = 5; 17 to 18 wk). The right bile duct was clamped between the liver and gall bladder. Bile samples were collected at 15-min intervals into microcentrifuge tubes (on ice) containing serine borate and iodoacetic acid to prevent glutathione oxidation. After two samples were obtained to establish baseline values, retrograde infusion of AT-125 (30 microLmol/kg BW) was given to inhibit gammaGT activity in the biliary tree. Systemic blood pressure of the birds remained above 100 mm Hg throughout each experiment (90 to 120 min). Bile flow did not change significantly during the experiment and ranged between 0.15+/-0.03 and 0.20+/ 0.07 mL/15 min per kg BW. Baseline biliary secretion values of reduced glutathione (GSH), oxidized glutathione (GSSG), and total glutathione (TGSH) were 4.6, 5.9, and 17 nmol/min per kg BW. After AT-125 infusion, biliary GSH levels increased from 15 to 31 nmol/min per kg BW, indicating that considerable gammaGT mediated catabolism of GSH occurred in the biliary tree of SCWL males. These results indicate that considerable turnover of GSH in the livers of domestic chickens is due to biliary excretion and that substantial recovery of GSH occurs through activity of gammaGT in the biliary tree. PMID- 11194049 TI - Mineral, amino acid, and hormonal composition of chicken eggshell powder and the evaluation of its use in human nutrition. AB - Chicken eggshell powder (ESP) might be an attractive source of Ca for human nutrition. To study its nutritional value, we analyzed minerals, amino acids, and hormones in commercially available Slovakian ESP. The mineral composition was compared with three Dutch ESP samples that differed in feed and housing, a Japanese ESP, refined CaCO3, and an oyster shell supplement. Chicken eggshell powder contains high levels of Ca (mean +/- SD/g EPS: 401+/-7.2 mg) and Sr (372+/ 161 microg) when compared with recommended or estimated daily intakes for humans 51 to 70 yr of age. Levels of potentially toxic Pb, Al, Cd, and Hg were very low as were levels of V, B, Fe, Zn, P, Mg, N, F, Se, Cu, and Cr. Large differences in the levels of F, Se, Cu, Cr, and Sr in the Dutch and Slovakian ESP indicated a strong influence of feed and environment. The small protein fraction of ESP contains high levels of Gly and Arg. Furthermore, small amounts of transforming growth factor-beta1 (0.75 to 7.28 ng/g ESP), calcitonin (10 to 25 ng/g ESP), and progesterone (0.30 to 0.33 ng/g ESP) were detected. Estradiol-17beta and calcitriol were below the detection limit of the methods used. Compared with ESP, refined CaCO3 was found to contain increased levels of Cd, and the oyster shell supplement showed increased levels of Al and Cd. Therefore, ESP seems to have a beneficial composition with about 39% of elemental Ca, relevant amounts of Sr, and low levels of Al, Pb, Cd and Hg. It may be used as a Ca source in human nutrition. PMID- 11194050 TI - Surface finishes on stainless steel reduce bacterial attachment and early biofilm formation: scanning electron and atomic force microscopy study. AB - Three common finishing treatments of stainless steel that are used for equipment during poultry processing were tested for resistance to bacterial contamination. Methods were developed to measure attached bacteria and to identify factors that make surface finishes susceptible or resistant to bacterial attachment and biofilm formation. Samples of the treated surfaces (sand-blasted, sanded, and electropolished) were exposed to natural bacterial populations from chicken carcass rinses to allow growth of bacteria and development of biofilms on the surfaces. The kinetics of bacterial growth during surface exposure was followed by UV-visible spectrophotometry, and counts of bacteria and early biofilm formation were measured following scanning electron microscopy (SEM). The surface morphology of the samples was analyzed by atomic force microscopy (AFM) with samples from each of the batches of treatments used in the SEM studies. Relative differences in the surface morphology, including fractal dimensions, Z ranges, roughness, and other measurements corresponded by treatment with the differences in reduction of bacterial counts shown by SEM. The surface types varied in affinity for bacteria, and both physical and electrochemical treatments improved resistance of stainless steel to bacterial attachment. Electropolished stainless steel was the least rough surface and showed significantly fewer bacterial cells and beginning biofilm formations than the other treated surfaces. Food safety could be improved if bacterial populations could be reduced during processing by increasing the use of materials that are resistant to bacterial contamination. These findings will aid equipment manufacturers and processors in selecting materials and finishes that are most resistant to bacteria and biofilm formation. PMID- 11194051 TI - Effect of dry honey on oxidation in turkey breast meat. AB - The effect of adding dry honey to turkey breast meat on oxidative stability was measured using TBA, volatile headspace, and oxidative stability index. Ground turkey breast meat was mixed with different concentrations of dry honey (0, 1, 5, 10, 15, and 20%) then cooked in polyethylene bags to 72 C. Oxidative stability measurements were taken for raw meat and cooked meat and for cooked meat after 48 h of storage at 4 C. The proximate composition of the raw meat was 73.9% moisture, 23.2% protein, and 1.3% fat. Gas headspace analysis determined hexanal to be the most abundant volatile compound. Hexanal content decreased as the amount of added honey increased in both freshly cooked meat and in meat stored for 48 h at 4 C. The TBA values also decreased with increasing levels of added honey in the freshly cooked and 48-h-stored meats. The percentage inhibition of oxidation for the 5, 10, 15, and 20% samples increased from 50 to 76% for the freshly cooked meat and from 34 to 88% for the 48-h-stored meat. The oxidative stability index increased with increasing concentrations of honey from 0.28 h (control) to 7.73 h (20% honey). Addition of up to 15% honey inhibited the development of oxidative compounds in cooked turkey meat, with little further inhibition observed compared to 20% honey. PMID- 11194052 TI - Shelf life of ground poultry meat stored under modified atmosphere. AB - The shelf life of ground chicken and turkey meat packaged under a modified atmosphere containing O2 and a high level of CO2 (62% CO2, 8% O2, and 30% N2; gas 1), or a gas mixture without O2 (20% CO2 and 80% N2; gas-2) was evaluated for 20 d at 1 C. Meat packaged under gas-2 maintained a higher a* value (redness) throughout the experiment and generally had a more appealing color than the meat packaged using gas-1. Microbial populations were assessed after 8, 12, and 15 d of storage. Total aerobic mesophilic counts were higher in chicken meat than in turkey throughout storage. Coliforms and Escherichia coli counts were lower in meat packaged under gas-1. After 15 d of storage at 1 C, Brochothrix thermosphacta was detected only in ground chicken meat packaged using gas-2. Meat packaged under the gas mixtures tested had similar counts for presumptive pseudomonads, Staphylococcus aureus, and lactic acid bacteria. These results indicate that an appropriate gas mixture can maintain a desirable color in ground poultry meat but offers no guarantees with respect to the microbial profile of meat. PMID- 11194053 TI - Validation of thiosulfate for neutralization of acidified sodium chlorite in microbiological testing. AB - At low pH, acidified sodium chlorite (ASC) has antimicrobial activity against a variety of foodborne contaminants. To evaluate the antimicrobial efficacy of ASC at specific time points posttreatment, it is necessary to halt the action of the disinfectant by removing residual chlorite or by increasing the pH. In this study, thiosulfate was investigated at varying concentrations for its effect on microbial survival and was investigated at a concentration of 0.1% in the presence of ASC for its effect on the antimicrobial and chemical activity of the test solution. Additionally, sodium thiosulfate was tested in two buffering systems, buffered peptone water (BPW) and Butterfield's phopshate buffer (BPB), for its ability to inactivate ASC chemistry. The results of this study show that, at a concentration of 0.1%, sodium thiosulfate has no deleterious effect on Escherichia coli survival and is effective in halting the antimicrobial action of ASC by eliminating the production of residual chlorite. The BPW alone and BPB in combination with thiosulfate were found to be effective inactivators of ASC chemistry. PMID- 11194054 TI - HeartSaver VAD: a totally implantable ventricular assist device. Results of in vivo studies. AB - Currently, the most widely utilized ventricular assist devices (VADs) require percutaneous connections and are located either externally (e.g., Thoratec, Abiomed) or intra-abdominally (e.g., Novacor, TCI). These attributes have been implicated in a variety of complications (infection, thromboembolic, gastrointestinal, etc.). To address these concerns, a totally implantable VAD that requires no percutaneous connections and can be implanted in the left hemi thorax has been developed. The developed device has undergone in vivo evaluation as part of the design and development process. A total of 43 implants in the bovine model, with 5 device versions, have been conducted between July 1992 and February 2000. These studies successfully have demonstrated several important aspects of the developed device, including 1) feasibility of a totally implantable system; 2) capability of the device to support a dysfunctional heart; and 3) ability of the device to provide flows up to 10 L/min in a physiological setting. The studies to date have played a vital role in the design and development process as well as demonstrating the feasibility of a totally implantable intrathoracic VAD. Based on these studies, design optimization was conducted, resulting in the development of the pre-clinical version of the device in preparation for clinical trials. PMID- 11194055 TI - In vitro comparison of inhibitors of inducible nitric oxide synthase in a macrophage model. AB - Nitric oxide (NO) has been shown to decrease cardiac performance, induce global hypotension, and generate oxygen free-radicals. Nitric oxide is produced from the conversion of L-arginine to L-citrulline by inducible nitric oxide synthase (iNOS) and is a component of many cellular second messenger systems. It is not clearly understood if NO and iNOS are compensatory mechanisms or pathological processes in heart failure, and this study was designed to understand better inhibition of iNOS in a cell culture model. Inhibitors of iNOS were compared for in vitro capability of inhibiting the production of NO. Ethanol and S methylisothiourea (MITU) were applied to macrophage populations in 120 microM and 1 microM, 100 and 10 nM for an 8-h incubation. Level of iNOS expression was measured in the ethanol-treated populations using an anti-iNOS primary antibody with a fluorescent labeled secondary antibody. Serum nitrites were measured in both treatment groups by the nonenzymatic Griess method to determine enzyme function. Our data indicate that ethanol demonstrates a stimulation and simultaneous inhibition of iNOS during an 8-h incubation. No dose-dependent correlation between amount of serum nitrites produced and ethanol treatment was observed. However, MITU demonstrated a clear inhibition of iNOS at 120 microM with a serum nitrite value of 25.7002 +/- 0.0647, with control values of 24.3421 microM. Lower concentrations of MITU also demonstrated no correlation. Although both agents display inhibitory effects upon iNOS, MITU seems to have no apparent simultaneous stimulation and may hold more potential as a post-translational inhibitor of iNOS. PMID- 11194056 TI - Co-administration of aprotinin and epsilon-aminocaproic acid during cardiopulmonary bypass in a swine model. AB - Despite the beneficial effects of pharmacological interventions to prevent bleeding and to reduce the need for autogeneic blood, there are concerns that these agents induce a prothrombotic state. The purpose of this study was to examine the coagulation phenomena influenced by the coadministration of epsilon aminocaproic acid (EACA) and aprotinin during cardiopulmonary bypass (CPB). A swine model of CPB was utilized in this study. During 120 min of CPB, treatment animals (N = 5) received 6 x 10(6) Kiu of aprotinin and 30 grams of EACA; whereas, control animals (N = 3) received an equal volume of 0.9% saline. Indices of thrombogenicity included hematological variables, gross pathology, and circuit examination for the presence of thrombus. The application of both antifibrinolytics resulted in an increase use of heparin. Total heparin requirements were significantly different between treatment group (58,800 +/- 3493 iu) versus control group (51,000 +/- 3464 iu). D-dimer concentration was also significantly higher in the control group (500-1000 ng mL-1) than in the treatment group (250-500 ng mL-1) at 5 and 30 min postprotamine. Other coagulation markers tested were not observed to be statistically significant between groups. Thromboelastographic (TEG) index decreased in the treatment group during the surgical procedure and bypass from 2.74 +/- 2.9 to -1.36 +/- 4.1 as compared to an increase from 2.62 +/- 2.9 to 4.05 +/- 0.4 in the control group. Pathologic analysis revealed occurrences of thrombus formation in small vessels in the lung and kidney glomeruli of treatment animals. The concurrent use of both aprotinin and EACA may induce a prothrombotic or coagulant state as determined by histological assessment. PMID- 11194057 TI - Technique for routine use of heparin bonded circuits with a reduced anticoagulation protocol. AB - The use of heparin-bonded cardiopulmonary bypass circuits (HBCs) with reduced anticoagulation protocol during cardiac surgery attenuates some of the adverse pathophysiologic responses to cardiopulmonary bypass (CPB). The strategies of how to maximize improvements in clinical outcomes using this technique are still debated. This article describes in detail a comprehensive approach to strategies developed at Boston Medical Center and the West Roxbury Veteran Affairs Medical Center in over 4000 cases in which HBC with a reduced anticoagulation protocol is used routinely. Important elements of this technique include elimination of cardiotomy reservoir during coronary artery bypass graft surgery (CABG), autologous blood priming, normothermic CPB, and precise heparin and protamine titration. Adaptation and variation in this technique to specific clinical situations is also highlighted. PMID- 11194058 TI - The effects of nitric oxide on coagulation during simulated extracorporeal membrane oxygenation. AB - Extracorporeal membrane oxygenation (ECMO) is associated with profound alterations in hemostasis, with platelet dysfunction often being implicated as a causative factor for transfusion. Nitric oxide (NO) has shown to be a rapid yet temporary inhibitor of platelet function. The purpose of this study was to evaluate the effects of NO on platelet number and function in an in vitro ECMO model. Eight silicone membrane oxygenators were primed with fresh, heparinized, bovine blood and allowed to circulate for 48 hours. The treatment group (NO) consisted of four oxygenators that had an end concentration of 20 ppm NO applied to the sweep gas. Platelet counts, methemoglobin levels, plasma-free hemoglobin levels, activated clotting times, and thromboelastographic (TEG) studies were performed at baseline, 1, 6, 12, and 24 h. Scanning electron microscopy (SEM) was performed on sample areas from each oxygenator. The treatment group maintained an average of 25% higher platelet counts than the control group (85.1 +/- 32.0, x 10(3) versus 66.5 +/- 30.9 x 10(3)) although statistical significance was not achieved. Methemoglobin levels were significantly elevated in the treatment circuit at hours 12 and 24 (p < .05). This could be attributed to the lack of a biological interaction that would break down this toxic by-product. TEG indices steadily declined in both groups from baseline (-0.4 +/- 3.6) to (-17.2 +/- 3.3 p < .0007) treatment and (-20 +/- 4.5, p < .0001) control, with the treatment circuit maintaining only slightly improved indices over the most of the study. SEM data showed increased fibrin and cellular deposits in the control group (p = .05) when compared with the treatment group. NO added to the sweep gas of a simulated ECMO circuit at 20 ppm had little effect on the maintenance of platelet number and function. PMID- 11194059 TI - A cardiopulmonary bypass perfusion technique for the surgical repair of aortic type I dissections requiring the elephant trunk procedure. AB - The effect of cerebral and spinal cord protection by a modified perfusion technique during the elephant trunk procedure was assessed. Between 1997 and 1998, six patients underwent selective cerebral perfusion (SCP) and lower half of the body perfusion (LBP), in which the right subclavian and left femoral arteries were separately cannulated and perfused by individual pump heads. Moderate systemic cooling was used (nasal temp. 20-30 degrees C; rectal temp. 23-26 degrees C). The open distal aortic repair was performed using only the selective cerebral perfusion; while the aortic arch reconstruction was performed using both selective cerebral and lower half of the body simultaneous perfusion. Blood oxygen saturation of the left jugular vein (SjO2) and regional oxygen saturation cerebral (rSO2) in the front region of the brain, was monitored along with the pressure of the left temporal superficial and femoral artery. The mean cardiopulmonary bypass time was 136 minutes, with a mean arrest time of 92 minutes. Mean duration of isolated selective cerebral perfusion was 23 minutes, with flow rates of 5-8 mL/kg/min; a left temporal superficial artery pressure of 50 mmHg; SjO2 65-80%, and rSO2 58-72%. Mean duration of simultaneous selective cerebral and lower half of the body perfusion was 27 minutes; cerebral flow rates 5-8 mL/kg/min; the left temporal superficial artery pressure of 45-50 mmHg; SjO2 70-85% and rSO2 55-76%. At the same time, lower half of the body flow rates were maintained within 30-50 mL/kg/min; with a femoral artery pressure 50-80 mmHg. Mean extubation time was 28 hours; mean ICU time was 4.5 days. There were no neurologic complications in any patient. All patients survived the operation and were discharged from the hospital. This modified perfusion technique of SCP and LBP worked well and provided satisfactory cerebral and spinal cord protection. PMID- 11194060 TI - Cost-benefit of trained transport teams: estimates for head-injured children. AB - INTRODUCTION: Care during transport influences the outcome of head-injured children. Secondary adverse events, e.g., hypotension and hypoxia, worsen morbidity and mortality. Trained transport teams lower the incidence of such secondary "insults." OBJECTIVE: To estimate the cost-benefit of improved care from trained escorts. METHODS: The setting was a provincial air ambulance service during transition to trained pediatric escort paramedics. A retrospective review of transport and hospital records for a 12-month period was conducted. All children with head injuries (n = 43) transported to tertiary care [11 by untrained escorts (UE), 32 by trained escorts (TE)] were enrolled. Severity of injury was classified by Glasgow Coma Score (GCS); incidence of adverse events was counted and cost of change of severity resulting from preventable insults was estimated using published care costs. RESULTS: There were 13 preventable insults in six patients (55%) in the UE group and five preventable insults in four patients (12%) in the TE group (p<0.05). Among those in the UE group, two changed in severity from moderate to severe, one moderate worsened (decrease in GCS of 2 or more), and two severe worsened. In the TE group, there were no changes >1. Cost-benefit estimates based on change in severity were $136,000 (median) to $238,000 (mean). CONCLUSION: Significant cost-benefit likely accrues from training escorts who transport children with significant head injuries to tertiary care. PMID- 11194061 TI - Patient status and time to intubation in the assessment of prehospital intubation performance. AB - Assessment of paramedic endotracheal intubation (ETI) performance often does not account for varied clinical conditions or the time required to complete the procedure. OBJECTIVE: To demonstrate the utility of patient status and time to intubation (TTI) for evaluating prehospital ETI performance. METHODS: Paramedic charts were reviewed for the period January-December 1998. Patient clinical status was defined as cardiac arrest (absence of perfusing rhythm) or non-cardiac arrest (presence of perfusing rhythm). Method, route, and success of ETI were noted. The TTI was determined as the elapsed time from on-scene arrival to securing of the endotracheal tube. Time elapsed from on-scene arrival to emergency department arrival was noted for instances of failed ETI. Statistical analysis was performed using chi-square and survival analysis (Kaplan-Meier estimator). RESULTS: Computer records were available for 26,026 patient contacts. Of 893 documented ETI attempts, 771 (86%) were successful. The ETI success rate was significantly higher (p<0.001) for cardiac arrests (551 of 591, 93.2%) than for non-cardiac arrests (220 of 302, 72.9%). Median TTIs were 5 minutes (95% CI: 5, 5) for cardiac arrests and 17 minutes (95% CI: 14, 20) for non-cardiac arrests; this difference was significant (p<0.001). For non-cardiac arrests, ETI success was significantly (p = 0.002) higher for orotracheal intubation (OTI) (168 of 214, 78.5%) than for nasotracheal intubation (NTI) (52 of 88, 59.1%). Median TTIs were 15 minutes (95% CI: 13, 17) for OTI and 25 minutes (95% CI: 23, 27) for NTI; this difference was significant (p = 0.002). For non-cardiac arrests, the difference i PMID- 11194062 TI - EMS dispatch. PMID- 11194063 TI - Which emergency medicine journals should EMS professionals read? PMID- 11194064 TI - Visits to home environments by emergency medical services: a statewide study. AB - Understanding out-of-hospital transport demographics would clarify the opportunities for injury surveillance and prevention. OBJECTIVE: To test the hypotheses that there are demographic differences in home vs. non-home emergency medical services (EMS) scene transports and that among age groups there are differences in demographics. METHODS: Data were extracted from the EMS State Ambulance Transport database of all reported during 1995. Transports from patient homes were compared with transports from all non-home scenes. Data extracted included age, gender, race, and type of complaint. Subgroup analysis was performed based on age groups in nonvehicular cases, safety problems, and interpersonal violence. Results were compared using a two-tailed chi-square with significance at p<0.05. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for significant differences. RESULTS: The study included 118,131 transported patients: 13% were children, 49% were adult between 18 and 64 years, and 38% were elder; 13% were African American, 82% were white, and 5% were other; 47% were male and 53% were female. Fifty-eight percent of the transports were for safety problems, and 17% were for interpersonal violence. Of the 118,131 transports, 56,812 (48%) were from patients' homes and 61,319 were not. Compared with EMS transports from non-home scenes, fewer home EMS transports were for injury (p<0.01, OR = 0.18, 95% CI = 0.17-0.19) and more home EMS transports were for illness (p<0.01, OR = 5.64, 95% CI = 5.49-5.79). There was no clinically significant difference in age, race, or gender. For all non-vehicular injury transports, the reason was more likely safety problems than interpersonal violence (58% vs. 17%); however, there was no difference in the percentages of type of call between the home and non-home transports. Home EMS transports were more likely interpersonal violence problems among adult patients less than 65 years old; however, among the old and young, the problems were more likely to be safety-related. CONCLUSION: Forty-eight percent of all EMS transports are from the home. Only 18% of these EMS home transports are for injury-related problems. In general, EMS injury transports are more likely related to safety than to interpersonal violence. Among the home EMS transports, more than 50% of transports for young and old patients are safety-related. A large proportion of the home EMS transports for adults less than 65 years of age, however, are for interpersonal violence. PMID- 11194065 TI - Diversion of ALS ambulances: characteristics, causes, and effects in a large urban system. AB - OBJECTIVE: To characterize the reasons for and effects of diversions of advanced life support (ALS) ambulances in a large urban area with a high concentration of receiving hospitals. METHODS: A retrospective study was performed in a large urban region during a consecutive three-month period. Diversion was defined as the ALS transport of a patient to an emergency department (ED) other than the designated primary receiving facility. Case-matched concurrent cohorts of patients who were and were not diverted were studied to establish emergency medical services (EMS) time intervals, including total prehospital interval (TPI), on-scene interval (OSI), and patient transfer interval (PTI); age; gender; Glasgow Coma Score (GCS); ALS interventions; and insurance status. The reasons for diversion and the chief complaints of diverted patients were also studied. RESULTS: During the study period, 2,534 ALS runs occurred, of which 147 (5.8%) were diverted. Twenty-four (16.3%) diversions had incomplete run times, leaving 123 (83.7%) for analysis. The most common chief complaints of diverted patients were shortness of breath (SOB), chest pain (CP), and altered mental status (AMS). The most common reason for diversion was special consideration (SC), defined as a diversion requested by a patient, family member, law enforcement officer, or private medical doctor. Diverted ambulances had significant increases in TPI, 36.4 [95% confidence interval (95% CI) 35.1-37.7] vs. 33.4 [95% CI 32.13-34.7], and PTI, 10.3 [95% CI 9.4-11.2] vs. 7.9 [95% CI 7.2-8.6], compared with nondiverted ambulances. Further analysis demonstrated that SC diversions accounted for all of the increases in TPI (p<0.001) and PTI (p<0.001) when compared with other types of diversions and nondiverted transports. CONCLUSION: "Special consideration" was the most common reason for diversion in this study. Special consideration diversions increased TPI and PTI, causing delays in arrival to the ED and decreased ALS ambulance availability. PMID- 11194066 TI - The emotional content and cooperation score in emergency medical dispatching. AB - BACKGROUND: A common belief regarding scripted-protocol-driven emergency medical dispatch is that the caller is "too hysterical" or "too uncooperative" to allow a structured interrogation or to receive and act upon dispatch life support instructions. OBJECTIVES: To examine the emotional content and cooperation scores (ECCSs) of callers in more than 6,000 cases from two communication centers and to investigate the relationships between ECCS and caller party, incident nature, time of day, and geographical location. METHODS: The ECCS has five levels: 5, uncontrollable, hysterical; 4, uncooperative, not listening, yelling; 3, moderately upset but cooperative; 2; anxious but cooperative; and 1, normal conversational speech. The authors tabulated the ECCS as recorded during case review for a random sample of each center's ongoing quality assurance programs. Statistical tests were used to identify the presence of relationships between ECCS and caller party, arrest/nonarrest situations, time of day, and geographical location. RESULTS: Regardless of the caller party, the type of call, the time of day, or the geographical location, the mean ECCS of emergency callers is extremely low, indicating that most emergency callers are, in fact, very calm. The average ECCS computed from more than 3,000 cases from British Columbia was 1.05; the average score from almost 3,500 cases from New York State was 1.21. CONCLUSION: While relationships between ECCS and the different parameters were noted, the differences were so small as to be of little or no use as additional information to assist with complaint triage. The low overall ECCS shows that the typical caller who requests emergency medical assistance is calm enough to be interrogated in a scripted and structured fashion, and is cooperative enough to be responsive to dispatch life support instructions. PMID- 11194067 TI - Utilization of air medical transport in a large urban environment: a retrospective analysis. AB - OBJECTIVE: To determine the utility of air medical transport in a large urban environment. METHODS: The authors conducted a retrospective analysis of all air medical transports of patients in the Fire Department of the City of New York EMS (emergency medical services) Command for the period of January 1, 1996, to December 31, 1999. These data were evaluated for frequency of air medical transport, patient condition at time of flight, and necessity of air evacuation. RESULTS: During the study period, some form of air medical transport was used 182 times. Of this number, 32 were for transports of patients from a scene of an incident to a hospital within New York City; 18 for interfacility transport of patients from a hospital facility within New York City to another facility within New York City; 122 for interfacility transfers of patients from medical facilities outside of the New York City area to a facility in New York City; and ten for transport of patients from New York City medical facilities to facilities out of the area. CONCLUSION: The Fire Department of the City of New York EMS Command utilizes air medical evacuation for patient transports very infrequently. The parameters of New York City's large urban environment may not be conducive to air medical transport. These data seem to be consistent with experiences of other large urban cities. PMID- 11194068 TI - Prehospital rapid-sequence intubation. PMID- 11194069 TI - Performance of retrograde intubation in a multiple-trauma patient. PMID- 11194070 TI - The closing and evacuation of Flagler County, Florida: rapid emergency medical services system response to a unique problem. PMID- 11194071 TI - Acute coronary syndrome: pharmacotherapy. AB - Acute coronary syndrome (ACS) refers to the spectrum of cardiac disease, from unstable angina to ST-segment-elevation myocardial infarction. In the emergency medical services (EMS) setting, ACS may be more broadly thought to include patients with chest pain or other symptoms believed to have a cardiac origin who have evidence of ischemia or acute myocardial infarction on a 12-lead electrocardiogram, or symptomatic patients with a previous cardiac event or known cardiac disease. Pharmacologic management of these patients is based on the use of three primary classes of drugs: those that affect clotting, those that establish and maintain hemodynamic control, and those that relieve pain. Many of these agents have been evaluated in large clinical trials for in-hospital use, and a number of ongoing studies are assessing their efficacy in the prehospital setting. The appropriateness of prehospital use of specific agents within each class depends on proper patient selection, the necessity of immediate intervention, ease of use in the field, expertise of EMS personnel, and cost effectiveness of therapy. This consensus group reviewed agents from all three classes (including aspirin, GPIIb/IIIa inhibitors, unfractionated and low molecular-weight heparins, fibrinolytics, beta-adrenergic blockers, calcium antagonists, nitrates, and morphine) for their overall indication, applicability to the prehospital setting, and current prehospital use. PMID- 11194072 TI - Predicting survival in pediatric trauma patients receiving cardiopulmonary resuscitation in the prehospital setting. AB - OBJECTIVES: To determine survival in pediatric trauma patients receiving cardiopulmonary resuscitation (CPR) in the prehospital setting and to identify subgroups of patients who may have increased survival rates. METHODS: Records were obtained from the National Pediatric Trauma Registry on all pediatric trauma patients (age <19 years) over an 82-month period who received CPR at the scene of the injury. Data were recorded as to type of injury, need for additional CPR at the receiving hospital, and intubation in the field. Patient outcome was defined as: dead on arrival, dead at trauma center discharge, or alive at trauma center discharge. Univariate and logistic regression analyses were performed to identify statistical differences in survivors compared with nonsurvivors. RESULTS: Seven hundred twenty-nine patients were identified. The median age was 7.0 years, with a mean of 7.9 years; 62% were male, 37% were female, and 1% had no gender recorded. Age and gender distributions were not statistically different for the three outcomes. Eighty-seven patients (12%) were dead on arrival and an additional 458 (63%) were dead at trauma center discharge, while 184 (25%) were alive at trauma center discharge. Motor vehicle crashes accounted for 27% of admissions, and pedestrians struck by vehicle accounted for 23%. Intentional violence accounted for 18% of the accrued patients. Predictors of death in the patients who were alive at admission were penetrating injury (p = 0.001) and requirement of additional CPR at the trauma center (p = 0.001). Prehospital intubation was associated with decreased survival. Of the 641 patients who arrived at the hospital alive, 29% lived to trauma center discharge, but of the 534/641 who received prehospital intubation, only 19% lived. The mean Functional Independence Measure (FIM) scores were 38.9 (range 18 to 126). CONCLUSIONS: Survival of pediatric trauma patients after receiving CPR in the prehospital setting is significantly higher than expected in adult patients. Penetrating trauma, the need for additional CPR at the trauma center, and prehospital intubation are all predictors of a worse outcome. PMID- 11194073 TI - Optimal prehospital cardiovascular care. AB - Optimal prehospital cardiovascular care may improve the morbidity and mortality associated with acute myocardial infarctions (AMIs) that begin in the community. Reducing the time delays from AMI symptom onset to intervention begins with maximizing effective patient education to reduce patient delay in recognizing symptoms and seeking assistance. Transportation delays can be minimized by appropriate use of 911 systems and improving technological 911 support. Patient triage to heart centers from the prehospital setting requires strict and comprehensive definition of the criteria for these centers by competent, unbiased clinical societies or governmental agencies. Prehospital 12-lead electrocardiograms and initiation of thrombolytic therapy can provide acute diagnosis and early treatment, thus facilitating faster processing and more directed in-hospital intervention. They also minimize over- and undertriage of patients to cardiac centers. Although evidence from investigational trials suggests that many of these procedures are effective, more research is required to ensure correct implementation and quality assurance at all emergency service levels. PMID- 11194074 TI - Concepts and application of prehospital ventilation. AB - Airway management and optimal ventilation are crucial aspects of managing out-of hospital medical emergencies. The goals in these situations are controlled ventilation and optimized inspiratory time, expiratory time, and airflow. Numerous techniques and devices are available to deliver oxygen-enriched air to patients during resuscitation. The bag-valve-mask (BVM) is one of the most common devices used to provide ventilation, although the American Heart Association ranks BVM devices lower in preference than other ventilation adjuncts, such as emergency and transport ventilators (ETVs) and pocket masks. The clearly documented limitations of BVM ventilation and its widespread use in the United States underscore the need to improve ventilation practices during care provided by emergency medical services (EMS) personnel. As part of that improvement, ETVs clearly have a role in the prehospital setting. These devices should be available on every ambulance, and the ability to use ETVs should be part of each EMS provider's skill set. Furthermore, all patients requiring emergency ventilation must be adequately monitored, including continuous monitoring of end-tidal carbon dioxide concentrations. As with any other skill, ventilation requires attention during initial training, continuing education and skill reinforcement, and quality review. PMID- 11194075 TI - Resuscitation in the out-of-hospital setting: medical futility criteria for on scene pronouncement of death. AB - The complete and irreversible cessation of life is often difficult to determine with complete confidence in the dynamic environment of out-of-hospital emergency care. As a result, resuscitation efforts often are initiated and maintained by emergency medical services (EMS) providers in many hopeless situations. Medical guidelines are reviewed here to aid EMS organizations with respect to decisions about: 1) initiating or waiving resuscitation efforts; 2) the appropriate duration of resuscitation efforts; and 3) recommended procedures for on-scene or prehospital pronouncement of death (termination of resuscitation). In cases of nontraumatic cardiac arrest, few unassailable criteria, other than certain physical signs of irreversible tissue deterioration, exist for determining medical futility at the initial encounter with the patient. Thus, the general medical recommendation is to attempt to resuscitate all patients, adult or child, in the absence of rigor mortis or dependent lividity. Conversely, wellfounded guidelines now are available for decisions regarding termination of resuscitation in such patients once they have received a trial of advanced cardiac life support. In practice, however, the final decision to proceed with on-scene pronouncement of death for these patients may be determined more by family and provider comfort levels and the specific on-scene environment. For patients with posttraumatic circulatory arrest, the type of injury (blunt or penetrating), the presence of vital signs, and the electrocardiographic findings are used to determine the futility of initiating or continuing resuscitation efforts. In general, patients who are asystolic on-scene are candidates for on-scene pronouncement, regardless of mechanism. With a few exceptions, blunt trauma patients with a clearly associated mechanism of lethal injury are generally candidates for immediate cessation of efforts once they lose their pulses and respirations. Regardless of the medical futility criteria, specialized training of EMS providers and targeted related testing of operational issues need to precede field implementation of on-scene pronouncement policies. Such policies also must be modified and adapted for local issues and resources. In addition, although the current determinations of medical futility, as delineated here, are important to establish for societal needs, the individual patient's right to live must be kept in mind always as new medical advances are developed. PMID- 11194077 TI - Liquid-based cytology for cervical screening. PMID- 11194076 TI - Spinal immobilization in the field: clinical clearance criteria and implementation. AB - Awareness of the health and financial repercussions of unnecessary immobilization has made cervical spinal immobilization controversial in out-of-hospital care. Clinical criteria for clearance of the cervical spine in the hospital based on mechanism of injury have been supported by many trauma centers. However, implementation of clinical criteria for cervical spinal clearance in out-of hospital settings is not as well validated by multicenter studies or accepted by many emergency departments. This consensus group recommends that clinical criteria to determine "low-risk" patients be available for use by emergency medical services providers in out-of-hospital settings; however, training, audits, quality management, integration into the medical community, and extent of program implementation should be decided based on individual emergency medical services systems. PMID- 11194078 TI - Cervical screening in England and Wales: its effect has been underestimated. AB - Opinions about cervical screening in the UK tend to follow one of two negative lines of thought. The first is that cervical cancer is a rare disease, and too much time and effort are spent on screening. The second is that it has been relatively ineffective, since incidence of invasive carcinoma did not fall until the NHS Cervical Screening Programme (NHSCSP) was introduced in 1988, although it fell by 40% since then. This paper presents publicly available data to demonstrate that neither of these views is true. Registrations of invasive carcinoma of the uterine cervix and carcinoma in situ in England and Wales between 1971 and 1996 show that a substantially increased risk of disease in women born since 1940 has been reversed, almost certainly by greatly improved screening. Cervical carcinoma is now a rare disease because most cases are prevented before they become invasive, mostly by screening young women, aged 20 40, before the decade of life when symptomatic cervical carcinoma most frequently presents. PMID- 11194079 TI - Ethnic factors in the pathology of the uterine cervix cervical screening: a population at variance with national targets. AB - In recent years, it has been noted that the rate of detection of high-grade uterine cervical abnormalities by screening in the Newham and Tower Hamlets districts have been much lower than the national average. Whilst the national average for the detection rate of moderate and severe dyskaryosis has been around 1.6%, the detection rate in Newham and Tower Hamlets has consistently been substantially lower, at 0.6-1.0%. This discrepancy may be explained on demographic grounds. The ethnic make up of the two districts differs from the national average. Newham has a mixed ethnic structure: Moslem (11%). Asian non Moslem (12%) and other groups (77%). The population of Tower Hamlets is made up of Moslem (23%), Asian non-Moslem ( 11%) and other groups (66%). In both districts, the rate of detection of moderate and severe dyskaryosis in these population subgroups between 1997 and 1999 was 0.57% for Moslem women, 0.52% for Asian non-Moslem women and 1.18% for other women. This study attempts to confirm the effects of social factors in the differences in rates of detection of cervical intraepithelial neoplasia (CIN) in Newham and Tower Hamlets. PMID- 11194080 TI - Survey of smear taking practice in the former North Thames region. AB - One hundred and seventy-seven doctors and 161 nurses from 230 clinics responded to a questionnaire on smear taking practice. The responses show that 66% of smear takers use the Aylesbury spatula and 30% use the Ayre spatula. A total of 53% use a cytobrush for selected cases. Training of smear takers and preparation of smears was satisfactory. Most (but not all) smear takers routinely record clinical information on the request form. Only 20 cytology laboratories in the North Thames region (70%) provide additional feedback to the smear takers about the quality of their smears apart from the information on the request form. Our study shows that feedback is an area where interaction between the laboratory and smear taker could be encouraged. PMID- 11194081 TI - Fine needle aspiration cytodiagnosis of secretory carcinoma of the breast. AB - Secretory carcinoma (SC) of the breast is a rare variant of breast malignancy and its cytological features in fine needle aspirates have only recently been described. In this communication, our experience with four cases of SC of the breast is presented in which the diagnosis was established on fine needle aspiration cytology (FNAC). In all cases, the samples were cellular and featured diffuse, prominent, intracytoplasmic vacuoles and secretion in malignant cells and occasional signet-ring like forms. The cytodiagnosis of SC in all the cases correlated with subsequent examination of cell blocks of the aspirate and tissue. Cytochemical stains showed diffuse positivity for mucin by alcian blue stain in the vacuolated cells which was periodic acid-Schiff positive and resistant to diastase digestion. Oil-red O staining was negative. Immunopositivity to carcinoembryonic antigen, cytokeratin (CAM 5.2), B72.3 and epithelial membrane antigen was found in malignant cells. The cytodiagnostic criteria for SC of the breast, characteristic cytological features which are useful in a correct FNAC diagnosis and differentiation from other pertinent breast carcinomas, are discussed. PMID- 11194082 TI - Validation of a decision support system for the cytodiagnosis of fine needle aspirates of the breast using a prospectively collected dataset from multiple observers in a working clinical environment. AB - We have used a 692 case dataset, collected retrospectively by a single observer, to develop decision support systems for the cytodiagnosis of fine needle aspirates of breast lesions. In this study, we use a 322 case dataset that was prospectively collected by multiple observers in a working clinical environment to test two predictive systems, using logistic regression and the multilayer perceptron (MLP) type of neural network. Ten observed features and the patient age were used as input features. The systems were developed using a training set and test set from the single observer dataset and then applied to the multiple observer dataset. For the independent test cases from the single observer dataset, with a threshold set for no false positives on the training set, logistic regression produced a sensitivity of 82% (95% confidence interval 73-91) and a predictive value of a positive result (PV +) of 98% (95-99), the values for the MLP were 79% (69-89) and 100%, respectively. However the performance on the prospective multiple observer dataset was much worse, with a sensitivity of 72% (65-80), and PV + of 97% (94-99) for logistic regression and 67% (60-75) and 91% (85-97) for the MLP. These results suggest that there is considerable interobserver variability for the defined features and that this system is unsuitable for further development in the clinical environment unless this problem can be overcome. PMID- 11194083 TI - Cytological findings in cystic hypersecretory ductal carcinoma of the breast: a potential pitfall in mammary cytology. PMID- 11194084 TI - Optimising FNA processing--a collection fluid allowing Giemsa, PAP and H & E staining, and facilitating thinprep, cytospin and direct smears and ancillary tests. PMID- 11194085 TI - The malpractice crisis. PMID- 11194086 TI - Influenza: a public health leadership meltdown. PMID- 11194087 TI - Medical care crisis looming in West Virginia. PMID- 11194088 TI - Breast cancer risks and prevention: implications of the Breast Cancer Prevention Trial results. AB - Breast cancer is a major health concern for women in the U.S. Several factors determine a woman's risk for developing breast cancer including age, genetics, hormonal exposure and others. It is possible to estimate a woman's risk for developing breast cancer by using a statistical model known as the Gail model. Using this model, the Breast Cancer Prevention Trial (BCPT) found that women at high risk for breast cancer could have their incidence of breast cancer reduced by 49% by taking tamoxifen. The serious side effects of tamoxifen therapy were almost exclusively seen in women over age 50. Women under 50 with a high risk of breast cancer are, therefore, most likely to benefit from taking tamoxifen for five years. Thus, a benefit-to-risk estimate should be made for each woman before advising her to take tamoxifen. A new trial (Study of Tamoxifen And Raloxifene, STAR) will compare tamoxifen with raloxifene for their effectiveness in reducing breast cancer and for side effects. West Virginia women participated in the BCPT and will be able to participate in the STAR trial through centers in Morgantown and Charleston. PMID- 11194089 TI - The STAR (Study of Tamoxifen and Raloxifene) trial in West Virginia. AB - Female breast cancer is a major medical problem with significant public health ramifications. In 1999, more than 170,000 women were diagnosed with breast cancer in the U.S. and more than 40,000 died from this disease. The STAR trial will determine if raloxifene (Evista) is either more or less effective than tamoxifen (Nolvadex in reducing the incidence of invasive breast cancer in postmenopausal women who are at increased risk for the disease. A secondary goal is to compare raloxifene and tamoxifen with regard to their side effects. Approximately 22,000 postmenopausal women, 35 years of age or older, who are at increased risk for developing breast cancer will be randomly assigned in this double-blind trial to receive either 20 mg of tamoxifen plus a placebo or 60 mg of raloxifene plus a placebo, for five years. A substudy to evaluate the effect of raloxifene and tamoxifen therapy on study participants' quality-of-life will also be conducted. PMID- 11194090 TI - The West Virginia Coalition for Quality Health Care: reducing variation and improving care. PMID- 11194091 TI - Recent advances in end-of-life care. PMID- 11194092 TI - Intradural convexity chondroma: a case report and review of diagnostic features. AB - Intradural convexity chondromas are slow-growing tumors of young adults and children. Their symptoms are due to their size and degree of mass effect. They are extra-axial, avascular masses without peritumoral edema. CT and magnetic resonance resonance imaging of the head and cerebral angiography are helpful in diagnosis. Treatment is surgical resection. PMID- 11194093 TI - Estrogen-induced relaxation in bovine coronary arteries in vitro: evidence for a new mechanism. AB - Numerous studies have shown estrogen to be vasoactive in various circulations. Our objective was to determine the effect of estrogen on isolated bovine coronary arteries and the possible mechanism. Bovine coronary arteries, precontracted with thromboxane mimetic U46619 were given doses (0.01-30 microM) of 17B-estradiol in the presence and absence of endothelium and these inhibitors: 10 microM indomethacin (cyclooxygenase inhibitor), 10 microM methylene blue (inhibits soluble guanylate cyclase), 100 microM nitro-L-arginine (inhibits nitric oxide synthesis), 100 microM isobutylmethylxanthine (phosphodiesterase inhibitor) and 30 microM mifepristone (Ru38486 steroid receptor antagonist). Our results indicated that, estrogen, in the highest concentration used (30 microM), elicited an acute dose-dependent relaxation of bovine coronary arteries from 4%-68% (n = 15). No major difference in relaxation was observed between coronary arteries with or without endothelium, indicating that the mechanism was endothelium independent. Indomethacin, nitro-L-arginine and methylene blue did not alter this relaxation, suggesting that relaxant prostaglandins, l-arginine products and cGMP are not involved (n = 11-16), isobutylmethylxanthine enhanced relaxation from 20% 40% (n = 15 p < 0.01), suggests a role for cAMP. Furthermore, mifepristone reduced the relaxation by more than 50% (n = 15 p < 0.05) consistent with the role for estrogen receptors. Based on our study, estrogen causes a dose-dependent relaxation of bovine coronary arteries that does not appear to utilize endothelium, prostaglandins, cGMP or arginine products, but may involve cAMP and estrogen receptors. This study may help justify treating myocardial ischemia with estrogen. PMID- 11194094 TI - Melanoma: latest diagnosis methods, surgical treatments and follow-up procedures. AB - Melanoma is a disease that is estimated will affect approximately 1 in 80 Americans. It is a potentially lethal cutaneous malignancy that requires initial diagnosis by full thickness incisional or excisional biopsy followed by appropriate surgical care. Prospective randomized studies for adjuvant therapy with intermediate (0.76-4 mm. Breslow depth), and deeper (4 mm. or greater Breslow depth) lesions will be discussed. This paper outlines an algorithm for lifelong postoperative clinical follow-up. PMID- 11194095 TI - Heart rate and blood pressure changes with endurance training: the HERITAGE Family Study. AB - PURPOSE: The purpose of this study was to determine the magnitude of change in resting and exercise heart rate (HR) and blood pressure (BP), by race, sex, and age, after a 20-wk endurance training program in 507 healthy and previously sedentary subjects from the HERITAGE Family Study. METHODS: After baseline measurements, subjects exercised on cycle ergometers 3 d x wk(-1) for a total of 60 exercise sessions starting at 55% of VO2max for 30 min x session(-1) and building to 75% of VO2max for 50 min x session(-1) for the last 6 wk. HR and BP at rest and during exercise (50 W, 60% of VO2max maximal exercise) were each determined in duplicate on two different days both before and after training (resting values at 24-h and 72-h posttraining). RESULTS: After the period of training, there was a small decrease in resting HR (-2.7 to -4.6 beats x min(-1) across groups at 72-h posttraining), and small changes (i.e., < 3 mm Hg) in resting systolic (SBP), diastolic (DBP), and calculated mean BP (MBP), which varied by race, sex, and age. During exercise at the same absolute work rate (50 W), HR, SBP, DBP, and MBP were all significantly reduced, with greater reductions in HR in women compared with men, and greater reductions in BP in blacks and older subjects compared with whites and younger subjects, respectively. At the same relative work rate (60% VO2max), HR, DBP, and MBP were reduced, but SBP remained unchanged. Blacks had a greater reduction in DBP, but whites had a greater reduction in HR. Finally, at maximal exercise, there was a small decrease in HR, with men and whites decreasing more than women and blacks; an 8 mm Hg increase in SBP, with men increasing more than women; a 4 mm Hg decrease in DBP, with blacks decreasing more than whites; and no change in MBP. CONCLUSION: In conclusion, the reductions in resting HR and BP with training were generally small, but the reductions during exercise were substantial and clinically important, with the older and the black populations experiencing greater reductions. PMID- 11194096 TI - Deficits in eccentric versus concentric torque in children with spastic cerebral palsy. AB - PURPOSE: The purposes of this study were to determine whether ambulatory children with spastic cerebral palsy (CP) had abnormal isokinetic eccentric peak torque values at the knee and ankle, and to gain further insights on the influence of spasticity on voluntary force production in this population. METHODS: Twenty-four children with spastic CP (mean = 11.1+/-2.6 yr) and twenty children of comparable age with no neuromotor pathology (mean = 10.3+/-2.6 yr) participated in an isokinetic testing protocol on a Biodex dynamometer that measured eccentric and concentric peak torques of the knee extensors, knee flexors, ankle dorsiflexors, and ankle plantarflexors. Angular velocity of the eccentric trials was 30 degrees x s(-1) and of the concentric trials was 30 degrees x s(-1), 60 degrees x s(-1), and 120 degrees x s(-1). Peak torque values were normalized by body weight and compared across groups by using ANOVA procedures. Eccentric to concentric (E/C) peak torque ratios at 30 degrees x s(-1) were computed for each muscle and compared across groups. The torque values in CP were also expressed as a percent of the mean normalized value of the comparison group and compared across conditions using repeated measures ANOVA (P < 0.05). RESULTS: Children with CP demonstrated decreased eccentric and concentric peak torques for all muscle groups tested. The relative deficit in eccentric torque was less than the concentric torque and the decrement in concentric torque across speeds was greater in CP for all muscle groups except the ankle dorsiflexors. The E/C ratios for the knee extensors and flexors were also greater in CP. CONCLUSIONS: Children with CP have diminished eccentric as well as concentric peak torques at the knee and ankle. The influence of spasticity on voluntary force production can be inferred from the bias toward greater eccentric torque and the greater decrement in concentric torque across speeds in children with spastic CP. PMID- 11194097 TI - Effect of knee joint effusion on quadriceps and soleus motoneuron pool excitability. AB - PURPOSE: To examine changes in quadriceps and soleus MN pool activity resulting from knee joint effusion over a 4-h period and assess the relationship between the muscles. METHODS: A repeated measures before-after trial design was used for this study. Eight, neurologically sound volunteers (age 23.3+/-2.1 yr, height 171.8+/-15.9 cm, mass 65.5+/-17.7 kg) participated in this study. An area superomedial to the patella was cleaned and anesthetized, and 30 mL of sterile saline was injected into the knee joint capsule to mimic mechanical joint effusion. The Hoffman reflex (H-reflex) was elicited by applying a percutaneous stimulus to the appropriate nerve and recording the response through surface electromyography. Soleus and vastus medialis H-reflex measures were collected from each volunteer before, at 30 min, 90 min, 150 min, and 210 min intervals over a 4-h period after knee effusion. RESULTS: All soleus H-reflex measures after effusion (30 min 5.89+/-0.92 V; 90 min 6.16+/-0.48 V; 150 min 6.59+/-0.50 V; 210 min 6.70+/-0.56 V) were increased in relation to the preeffusion measure (5.01+/-0.79 V). All vastus medialis H-reflex measures after effusion (30 min 4.23+/-0.94 V; 90 min 4.15 +/-1.11 V; 150 min 4.16+/-0.57 V; and 210 min 4.99+/ 1.23) were decreased in relation to the preeffusion measure (5.88+/-1.44 V; P < or = 0.05). CONCLUSIONS: Afferent activity from the knee joint capsule resulted in an inhibitory effect on the vastus medialis and a facilitatory effect on the soleus. Facilitation of the soleus in cooperation with other lower extremity musculature could be a mechanism for compensation of the inhibited quadriceps to maintain lower kinetic chain function. PMID- 11194098 TI - Knee biomechanics of the dynamic squat exercise. AB - PURPOSE: Because a strong and stable knee is paramount to an athlete's or patient's success, an understanding of knee biomechanics while performing the squat is helpful to therapists, trainers, sports medicine physicians, researchers, coaches, and athletes who are interested in closed kinetic chain exercises, knee rehabilitation, and training for sport. The purpose of this review was to examine knee biomechanics during the dynamic squat exercise. METHODS: Tibiofemoral shear and compressive forces, patellofemoral compressive force, knee muscle activity, and knee stability were reviewed and discussed relative to athletic performance, injury potential, and rehabilitation. RESULTS: Low to moderate posterior shear forces, restrained primarily by the posterior cruciate ligament (PCL), were generated throughout the squat for all knee flexion angles. Low anterior shear forces, restrained primarily by the anterior cruciate ligament (ACL), were generated between 0 and 60 degrees knee flexion. Patellofemoral compressive forces and tibiofemoral compressive and shear forces progressively increased as the knees flexed and decreased as the knees extended, reaching peak values near maximum knee flexion. Hence, training the squat in the functional range between 0 and 50 degrees knee flexion may be appropriate for many knee rehabilitation patients, because knee forces were minimum in the functional range. Quadriceps, hamstrings, and gastrocnemius activity generally increased as knee flexion increased, which supports athletes with healthy knees performing the parallel squat (thighs parallel to ground at maximum knee flexion) between 0 and 100 degrees knee flexion. Furthermore, it was demonstrated that the parallel squat was not injurious to the healthy knee. CONCLUSIONS: The squat was shown to be an effective exercise to employ during cruciate ligament or patellofemoral rehabilitation. For athletes with healthy knees, performing the parallel squat is recommended over the deep squat, because injury potential to the menisci and cruciate and collateral ligaments may increase with the deep squat. The squat does not compromise knee stability, and can enhance stability if performed correctly. Finally, the squat can be effective in developing hip, knee, and ankle musculature, because moderate to high quadriceps, hamstrings, and gastrocnemius activity were produced during the squat. PMID- 11194099 TI - Effects of walking poles on lower extremity gait mechanics. AB - PURPOSE: The purpose of this study was to determine whether walking with poles reduces loading to the lower extremity during level over ground walking. METHODS: Three-dimensional gait analysis was conducted on 13 healthy adults who completed 10 walking trials using three different poling conditions (selected poles, poles back, and poles front) and without the use of poles (no poles). The inverse dynamics approach was used to calculate kinetic data via anthropometric, kinematic, and kinetic data. RESULTS: All walking with poles conditions increased walking speed (P = 0.0001-0.0004), stride length (P < 0.0001), and stance time (P < 0.0001) compared with the no poles condition. There also was a decrease in anterior-posterior GRF braking impulse (P = 0.0001), a decrease in average vertical GRF walking with poles (P < 0.0001-0.0023), and a decrease in vertical (compressive) knee joint reaction force (P < 0.0001-0.0041) compared with the no poles condition. At the knee, extensor impulse decreased a 7.3% between the no poles and selected poles conditions (P = 0.0083-0.0287) and 10.4% between the no poles and poles back conditions (P < 0.0001). The support moment was reduced between the no poles and poles back (P = 0.0197) and poles front (P = 0.0002) conditions. Ankle plantarflexor work (A2) was reduced in the poles-front condition (P = 0.0334), but no differences were detected in all other ankle, knee or hip power and work variables (P > 0.05). CONCLUSION: There were differences in kinetic variables between walking with and without poles. The use of walking poles enabled subjects to walk at a faster speed with reduced vertical ground reaction forces, vertical knee joint reaction forces, and reduction in the knee extensor angular impulse and support moment, depending on the poling condition used. PMID- 11194100 TI - Energy expenditure during 2 wk of an ultra-endurance run around Australia. AB - PURPOSE: For ultra-endurance athletes, whose energy expenditure is likely to be at the extremes of human tolerance for sustained periods of time, there is increased concern regarding meeting energy needs. Due to the lack of data outlining the energy requirements of such athletes, it is possible that those participating in ultra-endurance exercise are compromising performance, as well as health, as a result of inadequate nutrition and energy intake. To provide insight into this dilemma, we have presented a case study of a 37-yr-old ultra marathon runner as he runs around the coast of Australia. METHODS: Total energy expenditure was measured over a 2-wk period using the doubly labeled water technique. RESULTS: The average total energy expenditure of the case subject was 6321 kcal x d(-1). Based on the expected accuracy and precision of the doubly labeled water technique the subject's total energy expenditure might range between 6095 and 6550 kcal x d(-1). The subject's average daily water turnover was 6.083 L over the 14-d period and might range between 5.9 L and 6.3 L x d(-1). CONCLUSIONS: This information will provide a guide to the energy requirements of ultra-endurance running and enable athletes, nutritionists, and coaches to optimize performance without compromising the health of the participant. PMID- 11194101 TI - Oligo-amenorrheic long-distance runners may lose more bone in spine than in femur. AB - PURPOSE: Strenuous training can be associated with amenorrhea leading to amenorrhea-related accelerated bone loss. Insufficient calorie energy, calcium, and/or protein intakes can also be frequently encountered in women with intense training, possibly contributing to bone loss. Long-distance runners with or without regular menses (age range 19-37 yr) were prospectively studied. METHODS: Changes in areal bone mineral density (BMD) were measured at 1-yr interval. RESULTS: Among 10 eumenorrheic, 11 oligo-amenorrheic, and 9 oral contraceptive users, there was no difference in energy, calcium, or protein intakes. Baseline BMD values were significantly lower in the oligo-amenorrheic group than in the two others at the level of lumbar spine (anteroposterior view: 0.941+/-0.039 in oligo-amenorrheic vs 1.077+/-0.029 or 1.051 +/-0.017 g x cm(-2), P < 0.005, in the eumenorrheic and contraceptive user groups, respectively) but not in weight bearing bone such as proximal and midshaft femur. Over a 1-yr interval, during which the three groups did not differ in terms of running distances and dietary intakes, oligo-amenorrheic women displayed a significant decrease in lumbar spine BMD in lateral view (-0.049+/-0.012 in oligo-amenorrheic vs -0.001+/-0.013 and 0.014+/-0.012 g x cm(-2), p < 0.005, in the eumenorrheic and contraceptive user groups, respectively). We did not detect any significant change in femoral neck, trochanter, or midshaft BMD. CONCLUSIONS: Oligo-amenorrhea in long-distance runners, with adequate dietary intakes, was associated with a decrease in BMD affecting more the lumbar spine than the proximal and midshaft femur during a 1 yr follow-up. PMID- 11194102 TI - Plasma lactate concentrations for self-selected maximal effort lasting 1 h. AB - PURPOSE: We determined the plasma lactate concentrations for 11 well-trained endurance cyclists or triathletes during a laboratory trial to measure maximal distance cycled in 1 h. METHODS: Subjects performed three distance trials, cycling as far as possible in 1 h. Blood samples were taken from a forearm vein every 10 min during the third trial (T). Samples were analyzed by spectrophotometer for plasma lactate concentrations ([La]). RESULTS: During T, subjects cycled 40.8+/-2.2 km at an average of 83+/-4% of their predicted maximum heart rate (HRmax). Minimum and maximum [La] for each subject was noted for minutes 10, 20, 30, 40, and 50. Minimum [La] ranged between 2.8 and 10.3 mmol x L(-1), and maximum [La] ranged between 5.8 and 13.6 mmol x L(-1). The average [La] from minute 10 to 50 was calculated for each subject and ranged from 5.0 to 12.3 mmol x L(-1). This did not correlate with performance (distance covered in 1 h). Therefore, there was a wide range of individual plasma lactate responses to the same laboratory test that simulated an actual race. The overall average [La] for all subjects was 7.6+/-2.1 mmol x L(-1). CONCLUSIONS: These data indicate first that the value of 4 mmol x L(-1), commonly referred to as OBLA, may often underestimate the upper limit of tolerance to lactate during a maximal endurance performance test lasting approximately 1 h. Second, during this type of work, intersubject differences in average plasma lactate concentration do not correlate with performance. PMID- 11194103 TI - Energy system contribution during 200- to 1500-m running in highly trained athletes. AB - PURPOSE: The purpose of the present study was to profile the aerobic and anaerobic energy system contribution during high-speed treadmill exercise that simulated 200-, 400-, 800-, and 1500-m track running events. METHODS: Twenty highly trained athletes (Australian National Standard) participated in the study, specializing in either the 200-m (N = 3), 400-m (N = 6), 800-m (N = 5), or 1500-m (N = 6) event (mean VO2 peak [mL x kg(-1)-min(-1)] +/- SD = 56+/-2, 59+/-1, 67+/ 1, and 72+/-2, respectively). The relative aerobic and anaerobic energy system contribution was calculated using the accumulated oxygen deficit (AOD) method. RESULTS: The relative contribution of the aerobic energy system to the 200-, 400 , 800-, and 1500-m events was 29+/-4, 43+/-1, 66+/-2, and 84+/-1%+/-SD, respectively. The size of the AOD increased with event duration during the 200-, 400-, and 800-m events (30.4+/-2.3, 41.3+/-1.0, and 48.1+/-4.5 mL x kg(-1), respectively), but no further increase was seen in the 1500-m event (47.1+/-3.8 mL x kg(-1)). The crossover to predominantly aerobic energy system supply occurred between 15 and 30 s for the 400-, 800-, and 1500-m events. CONCLUSIONS: These results suggest that the relative contribution of the aerobic energy system during track running events is considerable and greater than traditionally thought. PMID- 11194104 TI - Field evaluation of energy expenditure from continuous and intermittent walking in women. AB - RATIONALE: Recent physical activity recommendations suggest that comparable amounts of prescribed physical activity, done as a single continuous bout or as a set of intermittent bouts, will produce equal amounts of energy expenditure (EE) during the prescribed activity as well as throughout the day. HYPOTHESES: In a field setting, we tested two hypotheses: (1) continuous and intermittent walking conditions will result in significantly greater total daily EE than a control condition, and (2) continuous and intermittent walking conditions will result in similar total daily METHODS: Thirty women (mean age [yr] = 43.7+/-5.8; mean body mass index [kg x m(-2)]= 24.7+/-4.0) participated in a repeated-measures design so that each woman participated in three walking conditions on successive days of the week: a single 30-min brisk walk (continuous): three 10-min brisk walks (intermittent); and no activity (control). Throughout the study protocol, women wore a TRITRAC-R3D accelerometer programmed to estimate EE in 2-min intervals. RESULTS: Mean total EE estimates (kcal) for the three walking conditions were as follows: continuous: 2181+/-308; intermittent: 2121+/-305; and control: 1948+/ 270. A repeated-measures analysis of variance omnibus test indicated that EE differed significantly by experimental condition [F(2,58) = 40.2, P < 0.001). To test the first hypothesis, contrasts were examined revealing that EE in the continuous and intermittent conditions was significantly greater than EE in the control condition [F(1,29) = 58.2, P < 0.001]. To test the second hypothesis, contrasts revealed that EE in the continuous condition was significantly greater than EE in the intermittent condition [F(1,29) = 7.0, P = 0.013]. CONCLUSION: For the purposes of total EE, selecting a continuous mode of walking may offer additional benefit over an intermittent mode, given the same total prescribed duration. PMID- 11194105 TI - Validity of lower extremity strength and power utilizing a new closed chain dynamometer. AB - PURPOSE: The purpose of this study was to compare selected variables measured on a traditional isokinetic dynamometer (Cybex II) with a new lower extremity, closed chain dynamometer (Omnikinetic, OmK). METHODS: Twelve subjects (6 male, 6 female, age = 28+/-5 yr, mean +/- SD) performed Cybex II knee flexion and extension at 1.05, 3.14, and 5.23 rad x s(-1). A maximal effort of 10 repetitions of lower extremity concentric extension and eccentric flexion at 36% of subject's 1-RM was performed on the OmK. Crank power and joint (ankle, knee, and hip) kinetics were recorded as a mean of 10 repetitions. RESULTS: t-Tests revealed right versus left leg differences (P < 0.05) for Cybex II peak torque flexion at 5.23 rad x s(-1), and OmK knee and hip peak power and hip root mean square power (RMS) power. Cybex peak knee torques were related (Pearson r values 0.78-0.92, P < 0.01) to OmK peak knee torques. Cybex average power was related to OmK knee power (Pearson r values 0.71-0.96, P < 0.01) and OmK crank power (r = 0.62-0.94, P < .01). Correlations tended to be stronger comparing the OmK with the fastest (5.23 rad x s(-1)) Cybex II speed. CONCLUSIONS: These results suggest that the OmK knee and crank kinetic data are comparable to Cybex It isokinetic dynamometry. The ability to evaluate lower extremity joint exercise at a subject's maximal movement speed, in addition to the use of a closed-chain, multi joint motion, may allow for the OmK to provide a more global evaluation of lower extremity kinetics during seated concentric-extension, eccentric-flexion exercise. PMID- 11194106 TI - Exercise training with a heart device: a hemodynamic, metabolic, and hormonal study. AB - PURPOSE: The mechanisms of the training-induced improvements in left ventricular assist (LVAD) patients are unknown. METHODS: We measured the hemodynamic, gas exchange, and metabolic and hormonal effects of 6-wk exercise training in a cardiogenic shock patient who was assisted by an LVAD. RESULTS: After training, the peak power and VO2 increased by 166% and 56%, respectively (80 W and 16.1 mL x min(-1) x kg(-1)), whereas the ventilatory drive decreased. Although the LVAD output increased little with exercise, the systemic cardiac output rose (adequately for the VO2) from 5.91 and 4.90 L x min(-1) at rest to 9.75 and 9.47 L x min(-1) at peak work rate, before and after training, respectively. Thus, the left ventricle ejected again through the aortic valve. Unloading and/or retraining resulted in a left ventricular filling pressure decrease. Although the right ventricular ejection fraction increased with exercise, it decreased again at the maximal load after training. For a given work rate the arterial lactate, the norepinephrine (NE) and epinephrine (E) concentrations fell after training, but the enhanced maximal work rate elicited higher NE and E concentrations (4396 and 1848 pg x mL(-1), respectively). The lack of right ventricular unloading might have kept the atrial natriuretic peptide higher after training, but the blood cyclic GMP and endothelin were lower after training. CONCLUSION: In an LVAD patient, retraining returns the exercise capacity to the class III level by peripheral and left ventricular hemodynamic improvements, but the safety of maximal exercise remains to be proven in terms of right ventricular function and orthosympathetic drive. PMID- 11194107 TI - Effect of elbow joint angle on the magnitude of muscle damage to the elbow flexors. AB - PURPOSE: It has been shown that eccentric actions at a long muscle length result in a larger decrease in force and more muscle tenderness compared with those at a short muscle length. To further investigate the effect of elbow joint angle on the development of muscle damage, this study compared two maximal eccentric exercise regimens in which the starting position of the action was different, but the range of movement was the same. METHODS: One arm of 10 male students performed 24 maximal eccentric actions of the elbow flexors at the elbow joint angle from 0.87 to 2.27 rad (50-130 degrees: S condition) and the other arm at the elbow joint angle from 1.74 to 3.14 rad (100-180 degrees: L condition). Maximal isometric force, range of motion, muscle soreness, plasma creatine kinase activity, upper arm circumference, and B-mode ultrasound pictures of the elbow flexors (US) were measured before and for 5 d postexercise in both conditions. Magnetic resonance imaging (MRI) of the transverse scans of the upper arm was taken at 4 d after exercise. RESULTS: All measures changed significantly (P < 0.01) after exercise for both conditions; however, significantly (P < 0.01) larger changes in the measures were found in the L condition compared with the S condition. MRI and US displayed that only the brachialis was damaged for the S condition but the biceps brachii was also damaged for the L condition. CONCLUSION: The greater development of muscle damage in the L condition compared with the S condition is likely to be associated with the elbow flexors muscles affected by the exercise. PMID- 11194108 TI - Habitual physical activity in children and adolescents with cystic fibrosis. AB - PURPOSE: This study was conducted to: 1) measure total physical activity levels, including the intensities of the various types of activities, in children and adolescents with CF compared with non-CF healthy control subjects; and 2) determine whether vigorous activity level was related to aerobic fitness and disease status in patients with CF. METHODS: Thirty patients with CF (18 male, 12 female) and 30 control subjects (17 male, 13 female), 7-17 yr old, participated in this study. Habitual physical activity was measured using Kriska's Modifiable Activity Questionnaire (MAQ) and the past year's average of total hours, MET hours, and vigorous (VIG) hours (>6 METs) of activity per week were determined. Aerobic fitness was determined from peak oxygen uptake (VO2peak) obtained via maximal exercise testing on a cycle ergometer. Standard spirometry was used to measure pulmonary function. Body mass index (BMI) was determined from height and weight measurements. RESULTS: The CF and control groups were similar in age and gender distribution, but the patients were smaller (BMI, 98 vs 112% of predicted) and less aerobically fit (36.5 vs 41.4 mL x kg(-1) x min(-1)). Total and MET hours of physical activity did not differ between groups; however, the CF group participated in significantly fewer hours of vigorous activities than the control group (2 vs 3.7 h x wk(-1)). In patients with worse lung disease, VIG-h x wk(-1) were significantly related to VO2peak (r = 0.83). CONCLUSION: These results suggest that children with CF engage in less vigorous physical activities than their healthy non-CF peers, despite having good lung function. In view of the progressive nature of the disease, and the association between aerobic fitness and vigorous activity, patients should be encouraged to engage in more vigorous activities that promote aerobic fitness and may ultimately have an impact on survival. PMID- 11194109 TI - Treatment of exercise-induced muscle injury via hyperbaric oxygen therapy. AB - PURPOSE: This study examined the role of hyperbaric oxygen therapy (HBO) in the treatment of exercise-induced muscle injury. METHODS: 21 college-aged male volunteers were assigned to three groups: control, immediate HBO (iHBO), and delayed HBO (dHBO). All subjects performed 6 sets (10 repetitions per set) of eccentric repetitions with a load equivalent to 120% of their concentric maximum. HBO treatments consisted of 100-min exposure to 2.5 ATA and 100% oxygen with intermittent breathing of ambient air (30 min at 100% O2, 5 min at 20.93% O2). HBO treatments began either 2 (iHBO) or 24 h (dHBO) postexercise and were administered daily through day 4 postexercise. Forearm flexor cross-sectional area (CSA) and T2 relaxation time via magnetic resonance imaging (MRI) were assessed at baseline, 2, 7, and 15 d postinjury. Isometric strength and rating of perceived soreness of the forearm flexors were assessed at baseline, 1, 2, 3, 4, 7, and 15 d postinjury. Serum creatine kinase (CK) was assessed on day 0 and on days 1, 2, 7, and 15 postinjury. RESULTS: Mean baseline CSA values were: 2016.3, 1888.5, and 1972.2 mm2 for control, iHBO, and dHBO, respectively. All groups showed significant increases in CSA in response to injury (21% at 2 d, 18% at 7 d) (P < 0.0001), but there were no significant differences between groups (P = 0.438). Mean baseline T2 relaxation times were: 26.18, 26.28, and 27.43 msec for control, iHBO, and dHBO, respectively. Significant increases in T2 relaxation time were observed for all groups (64% at 2 d, 66% at 7 d, and 28% at 15 d) (P < 0.0001), but there were no significant differences between groups (P = 0.692). Isometric strength (P < 0.0001), serum CK levels (P = 0.0007), and rating of perceived soreness (P < 0.0001) also indicated significant muscle injury for all groups, but there were no differences between groups (P = 0.459, P = 0.943, and P = 0.448, respectively). CONCLUSION: These results suggest that hyperbaric oxygen therapy was not effective in the treatment of exercise-induced muscle injury as indicated by the markers evaluated. PMID- 11194110 TI - Alcohol and college athletes. AB - PURPOSE: This study examines heavy episodic alcohol consumption and associated harms in collegiate athletes in the United States. The factors which may promote or deter such use are explored. METHODS: Randomly selected students in a nationally representative sample of 4-yr colleges in the United States completed self-report questionnaires in the spring of 1997. Athletes were defined as students who participated in one or more hours of intercollegiate athletics per day. Heavy episodic or "binge" drinking for men was defined as consuming five or more alcoholic drinks on at least one occasion in the past 2 wk and four or more for women. Athletes were compared with other students at their colleges. RESULTS: Athletes reported more binge drinking, heavier alcohol use, and a greater number of drinking-related harms. Athletes are more likely to exhibit the strong social ties found to be associated with binge drinking. Athletes, despite drinking more heavily than other students, report greater exposure to alcohol prevention efforts and possess unique motivations to limit their alcohol use. CONCLUSIONS: Athletes are a high-risk group for binge drinking and alcohol-related harms. Although special educational programs have targeted this group they have not sufficiently impacted the problem. Future prevention efforts targeted for athletes should address the unique social and environmental influences on athletes. Programs should also take advantage of motives of athletes for self limiting alcohol intake. Colleges, athletic departments, coaches, and sports medicine professionals are urged to act to help reduce athletes risk of alcohol related harms. PMID- 11194111 TI - Effect of swim taper on whole muscle and single muscle fiber contractile properties. AB - PURPOSE: To examine the changes in whole muscle function and single cell contractile properties of Type I and II muscle fibers from the deltoid muscle of highly trained swimmers before and after a 21-d reduction in training volume (taper). METHODS: Six college male swimmers (age, 20+/-1 yr; height, 187+/-2 cm, weight, 79+/-3 kg, fat, 7+/-1%) who had been, on average, swimming 6200 m x d(-1) for 5 months before the taper participated in this investigation. RESULTS: Whole muscle power increased (P < 0.05) 17% and 13% on the swim bench and swim power tests, respectively. Swim times improved by 4% (range: 3.0-4.7%; P < 0.05). There was no change in Type I fiber diameter, whereas Type IIa fibers were 11% larger (P < 0.05) after taper. Peak force (Po) of the Type I fibers was unaffected by the taper but increased (P < 0.05) from 0.63+/-0.02 to 0.82+/-0.05 mN in the IIa fibers. However, the specific force (Po/CSA) of the IIa fibers was unchanged. Shortening velocity (Vo) was 32% and 67% faster (P < 0.05) in the Type I and IIa fibers, respectively. Although Type I fiber power was unaltered, the IIa fibers increased 2.5-fold from 24.6+/-2.8 to 56.2+/-3.9 microN x FL x s(-1). When power was normalized for cell size, the power was still elevated twofold. CONCLUSIONS: These data suggest that tapering induces alterations in the contractile properties of single muscle fibers. Further, it appears that the Type IIa fibers are more affected than the Type I fibers by the taper. The increased size, strength, velocity, and power of the IIa fibers may be responsible for the improvements in whole muscle strength and power after the taper. PMID- 11194112 TI - Effects of light physical exercise on sleep regulation in rats. AB - PURPOSE: Acute physical exercise is known to enhance slow-wave sleep (SWS) and reduce paradoxical sleep (PS) in humans. In this study, we examined the effects of moderate physical exercise on sleep in rats. METHOD: Young adult Wistar rats underwent a 4-h baseline electroencephalographic (EEG) recording session. The following day, they were induced to walk (0.8 m x min(-1)) or run (4 m x min(-1)) for 45 min in a rota-rod treadmill. Active control rats (ACR) were placed on the locked rota-rod for 45 min, whereas passive control rats (PCR) remained in their home cages. They were then left free to sleep for 4 h during which EEG activity was recorded. Rectal temperature (Tre) was monitored before and after exercise in ACR, walking and running rats (WR and RR, respectively) and at 45 min intervals in PCR. RESULTS: WR were able to walk for 45 min consecutively whereas in RR performances differed. Posttraining Tre was unchanged in ACR, PCR, and WR and resulted about 1.8 degrees C above baseline in RR. In both WR and RR after exercise i) length of SWS and PS, ii) intensity of SWS (spectral power density in 1-4 Hz range), and iii) propensity for falling asleep were enhanced. Interestingly, there was a more conspicuous increment in PS than SWS. In ACR and PCR there were no changes in sleep. CONCLUSIONS: Due to the complexity of sleep regulation, the interaction of several factors might underlie the observed increment in SWS and PS. Nevertheless, it is interesting that light physical exercise favors sleep and above all a harmonic enhancement of both sleep phases. PMID- 11194113 TI - Creatine supplementation affects muscle creatine during energy restriction. AB - INTRODUCTION: Anaerobic performance and body protein may decrease with energy restriction practiced by some athletes for weight loss. METHODS: This investigation examined the effects of creatine (Cr) supplementation during energy restriction on muscle Cr, exercise performance (10 sprints of 6 s, with 30-s rest), nitrogen balance, and body composition in male resistance trainers. Creatine supplemented (CrS, 20 g x d(-1) of Cr) and those given a placebo (P1) consumed a formula diet of 75.3 kJ (18 kcal) x kg(-1) x d(-1) (54.7% C, 21.3% P, 24% F) for 4 d. A control group was unsupplemented and continued their normal diet. There were no changes in body composition or performance of the control group. RESULTS: CrS and P1 demonstrated similar decreases in body weight and percent body fat. The percent change in fat-free mass was more for P1 (2.4+/-0.3% reduction) than CrS (1.4+/-0.4%), but urinary nitrogen losses were similar. Significant increases in muscle total Cr and CrP of 15-16% were demonstrated by CrS over the energy restriction period, whereas P1 had no changes in muscle Cr. Total work done during the sprints expressed per body weight tended to be 3.8% higher in CrS and 0.5% less in P1 after the energy restriction (P = 0.058). CONCLUSION: It was concluded that Cr supplementation increased muscle Cr during short-term energy restriction but did not affect body fat or protein loss. The change in muscle creatine was reflected in a tendency for higher total sprint work for the Cr group. PMID- 11194114 TI - The influence of diet and exercise on muscle and plasma glutamine concentrations. AB - PURPOSE: This study examined the relationship between muscle glutamine, muscle glycogen, and plasma glutamine concentrations over 3 d of high-intensity exercise during which dietary carbohydrate (CHO) intake varied. METHODS: Five endurance trained men completed two exercise trials in randomized order, over a 14-d period. Each trial required subjects to perform 50 min of high-intensity continuous and interval exercise on three consecutive days while consuming a diet that provided 45% of the energy as CHO or a diet in which CHO provided 70% of the total energy. Four days of inactivity and consumption of a 55% CHO diet separated the two randomized trials. Menus and food were provided for the subjects and all food and drink consumed were weighed and recorded for later analysis. Before exercise on the first day of each trial, at the start of exercise on day 3 and on completion of exercise on day 3, muscle was biopsied from the vastus lateralis for the analysis of glutamine and glycogen concentrations. Venous blood was sampled before and twice after exercise on each day for the analysis of plasma glutamine and cortisol concentrations. RESULTS: Mean plasma glutamine concentration was significantly higher during the 70% CHO exercise trial when compared with the 45% CHO trial (P < 0.05). Glycogen decreased by the same magnitude during both trials and there was no relationship between changes in plasma glutamine and changes in muscle glycogen concentration. Muscle glutamine concentration did not change in either trial. CONCLUSIONS: These data suggest that the influence of carbohydrate intake upon the concentration of plasma glutamine is not mediated through the concentration of intramuscular glycogen. PMID- 11194115 TI - Maximal exercise as a countermeasure to orthostatic intolerance after spaceflight. AB - Previous investigators have suggested that maximal exercise performed 24 h before the end of bed rest, a spaceflight analog, restores prebed rest plasma volume, baroreflex responses, and orthostatic tolerance. PURPOSE: In this case report, we examined the effect of a similar exercise protocol 24 h before a Shuttle landing on the orthostatic responses of four crewmembers (EX) after spaceflights of 8-14 d. Four additional crewmembers (CON) served as controls and did not perform exercise during the final day of the flight. METHODS: Each crewmember performed a 10-min stand test approximately 10 d before launch (L-10) and within 1-2 h of landing (R+0). Cardiac stroke volume was measured (Doppler ultrasound) supine and during each min of standing for three EX and three CON subjects. RESULTS: Preflight, all crewmembers completed the stand test and each group had similar heart rate and blood pressure responses. Postflight, all subjects also completed the 10-min stand test. Each group had similarly elevated supine and standing heart rates, elevated diastolic and mean arterial blood pressures, and reduced pulse pressures compared to L-10. However, postflight cardiac output, mean +/- SEM, (EX: 4.5+/-0.6 L x min(-1); CON: 3.1+/-0.3 L x min(-1)) and stroke volume (EX: 43+/-7 mL x beat; CON: 30+/-6 mL x beat) were higher after 10 min standing in the EX subjects compared to CON subjects. CONCLUSIONS: For these four crewmembers, maximal exercise performed 24 h before landing may have helped maintain stroke volume but did not maintain heart rate and blood pressure responses during standing compared to preflight. PMID- 11194116 TI - Vascular smooth muscle: integrator of vasoactive signals during exercise hyperemia. AB - The primary focus of this review is to discuss the importance of vascular smooth muscle function in mechanisms underlying exercise hyperemia in skeletal muscle. Important features of exercise hyperemia are presented and include: 1) the large magnitude of increase in blood flow, 2) the pattern of increased blood flow within and among skeletal muscle during exercise, 3) exercise hyperemia results from increases in vascular conductance produced by relaxation of vascular smooth muscle, 4) the increased blood flow is linked to the oxidative metabolism of the muscle, and 5) the increased blood flow occurs very rapidly with the initiation of exercise. A prevailing theme throughout this review is that vascular smooth muscle is a primary integrator of vasoactive signals that, in turn, regulate vascular resistance and muscle blood flow. Signal transduction pathways involved in vascular smooth muscle contraction and relaxation are discussed, with particular emphasis on the role of multiple and redundant signaling pathways for initiating a given contractile/relaxation response. We emphasize the concept that exercise hyperemia is a local phenomenon and that, during maximal exercise when most signals for vasoconstriction are still present, three primary control mechanisms are thought to regulate vasodilation and subsequent increases in vascular conductance: myogenic vascular control, metabolic vascular control, and endothelium-mediated vascular control. Experimental paradigms to test the relative importance of the predominant mechanisms thought to underlie exercise hyperemia are discussed and evaluated in light of the multiple and redundant control systems now known to contribute to control of blood flow in striated muscle tissue. PMID- 11194117 TI - An effective, economic way of monitoring menstrual cycle hormones in at risk female athletes. AB - PURPOSE: Female athletes, in response to intensive training, competition stress and a lean, athletic physique, are at increased risk of altered hypothalamic pituitary ovarian (HPO) axis function associated with menstrual cycle disturbance and reduced secretion of the ovarian hormones estrogen and progesterone. Because there is evidence suggesting possible detrimental effects on skeletal health associated with deficiencies in these hormones, a suitable means to asses ovarian hormone concentrations in at risk athletes is needed. The aim of this study was to evaluate a simple, economical means to monitor the ovarian hormone production in athletes, in the setting of intensive training. METHODS: Subjects comprised 14 adolescent rowers, 12 lightweight rowers, and two groups of 10 matched control subjects. Ovarian function was monitored during the competition season by estimation of urinary excretion of estrone glucuronide (E1G) and pregnanediol glucuronide (PdG), enabling the menstrual cycles to be classified as ovulatory or anovulatory. RESULTS: Results indicated 35% and 75% of schoolgirl and lightweight rowers had anovulatory menstrual cycles, respectively. These findings were highlighted by significantly lower excretion of E1G and PdG during phases of intensive training in both the lightweight and schoolgirl rowers, compared with the control subjects. CONCLUSION: It was concluded that the urinary E1G and PdG assays were an effective means to assess the influence of intense training on ovarian hormone concentrations in at risk athletes. It is recommended that this technique be applied more widely as a means of early detection of athletes with low estrogen and progesterone levels, in an attempt to avoid detrimental influences on skeletal health. PMID- 11194118 TI - Exercise training increases creatine kinase capacity in canine myocardium. AB - INTRODUCTION: The creatine kinase (CK) energy shuttle of cardiomyocytes channels metabolic energy from the mitochondria to sites of energy utilization at contracting myofibrils and sarcolemmal and sarcoplasmic reticular ion pumps. Although plasticity of the myocardial CK system in response to hemodynamic overload has been repeatedly demonstrated, the effects of aerobic exercise training on myocardial CK are less well understood. This investigation tested the hypothesis that aerobic exercise training increases the capacity of the CK system in canine myocardium. METHODS: Mongrel dogs were conditioned by a 9-wk treadmill running program or cage-rested for 4 wk. Total CK activity was measured colorimetrically; CK(MB) was separated from other CK isoforms and measured by electrophoresis. RESULTS: Relative to sedentary controls, training increased left ventricular total CK activity 46% (P < 0.05) but did not alter total CK activity in right ventricular myocardium. Also in left ventricular myocardium, training increased CK(MB) isoenzyme activity 4.5-fold and the CK(MB) fraction of total CK threefold from 1.1+/-0.4 to 3.4+/-0.8% (P < 0.05). In contrast to left ventricle, CK(MB) activity and its fraction of total CK activity were not altered by training in right ventricular myocardium. CONCLUSIONS: Aerobic exercise training increases total myocardial CK activity and CK(MB) content in canine left ventricular myocardium, although CK(MB) remains a minor component of the myocardial CK system. The right ventricular CK system was not affected by training. PMID- 11194119 TI - Cardiac output and stroke volume changes with endurance training: the HERITAGE Family Study. AB - PURPOSE: The purpose of this study was to determine the magnitude of changes in cardiac output (Qc), stroke volume (SV), and arterial-mixed venous oxygen difference (a-vO2 diff) during submaximal exercise following a 20-wk endurance training program, with the primary focus on identifying differences in response by race, sex, and age. METHODS: The participants in this study (N = 631) were healthy and previously sedentary men (N = 277) and women (N = 354) of varying age (17-65 yr) and race (blacks, N = 217; whites, N = 414) who had completed the HERITAGE Family Study protocol. After baseline measurements, participants trained on cycle ergometers 3 d x wk(-1) for a total of 60 exercise sessions starting at the HR associated with 55% of maximal oxygen uptake (VO2max) for 30 min/session and building to the HR associated with 75% of VO2max for 50 min/session, which was maintained during the last 6 wk. HR, Qc (CO2 rebreathing), and SV (Qc/HR) were determined in duplicate at 50 W and at 60% of VO2max on two different days both before and after training. RESULTS: After training, there were significant decreases in HR and Qc, and significant increases in SV and a-vO2 diff at 50 W (except for no change in a-vO2 diff in black men). The changes in HR differed by sex and age, and the changes in SV, Qc, and a-vO2 diff differed by race. Qc decreased by 0.6 L x min(-1) at 50 W for the total sample, consistent with the decrease in VO2 at this power output. At 60% of VO2max HR decreased, and SV, Q, and a-VO2 diff increased. There were small differences in response by sex (HR and SV), race (HR), and age (HR and Qc). CONCLUSION: It is concluded that the cardiovascular systems of men and women, blacks and whites, and younger and older subjects are not limited in their ability to adapt to endurance training. PMID- 11194120 TI - Assessment of the Massachusetts Behavioral Health Program Year 6. AB - After a difficult transition from the previous vendor to the Massachusetts Behavioral Health Partnership (MBHP), Year 6 was a year of stability and incremental changes for the Massachusetts Behavioral Health Program. This assessment of Year 6 is based on interviews with key players, data provided by the MBHP, a survey of providers, as well as on the fifth year of an ongoing review of the program. Results indicate that enrollment grew, and new services were developed in response to identified needs. Providers considered access, utilization, and quality of care to be the same or better than a year earlier. Coordination improved, but was not optimal. Clinical and overall decisions with MBHP were collaborative or negotiated and less hierarchical in manner than the previous year. Providers rated MBHP better than other managed care organizations on quality of care and utilization review decisions, access, flexibility, and administration. PMID- 11194121 TI - Playing policy pinball: making policy analysis palatable. AB - The author presents a teaching tool to make policy analysis accessible to a wide range of audiences, especially those who might normally be reluctant to engage in policy discussions or debate. The tool has been used with good results in a variety of venues, and is presented with brief examples of how it can be used. PMID- 11194122 TI - The evolution of mental health parity in American politics. PMID- 11194123 TI - Trauma within the psychiatric setting: conceptual framework, research directions, and policy implications. PMID- 11194124 TI - Managed care and service capacity development in a public mental health system. AB - Developing a continuum of care is considered to be one of the first steps in the process of implementing managed care strategies. This study summarizes the results of a final survey that focused on the ability of Colorado community mental health centers (CMHCs) to build service capacity and create new programs as a result of Medicaid capitation financing. Capitated agencies, compared to those that remained fee-for-service during the study period, reported a much greater ability to develop services as a result of capitation. Decreases in services were minimal for all agencies. Some differences in managed care organizational models were noted, as were differences in the speed of implementation. Gaps in some services still remain. These findings point to important program implementation issues for publicly funded managed care. PMID- 11194125 TI - Enhancing inter-network cooperation among organizations providing mental health services to older persons. AB - The authors examine how organizations in several networks voluntarily cooperate to provide mental health services to older persons and recommend how organizational coordination and the delivery system can be improved. Information from mail surveys and in-depth interviews was analyzed. Little evidence of formal coordination across networks was found. Established organizations and agencies providing a larger number of services were more integrated. Providers recommended that organizational coordination be increased. Providers suggested that a more centralized delivery system and proactive education for clients and providers would be effective strategies to enhance service delivery. PMID- 11194126 TI - Performance measures of cultural competency in mental health organizations. AB - The authors utilized numerous documents created by advisory groups, expert panels and multicultural focus groups to develop performance measures for assessing the cultural competency of mental health systems. Competency was measured within three levels of organizational structure: administrative, provider network, and individual caregiver. Indicators, measures and data sources for needs assessment, information exchange, services, human resources, plans and policies, and outcomes were identified. Procedures for selection and implementation of the most critical measures are suggested. The products of this project are broadly applicable to the concerns of all cultural groups. PMID- 11194127 TI - Alosetron withdrawn from market. PMID- 11194128 TI - Needlestick prevention measures become law. PMID- 11194129 TI - Companies try different plans for same clotting factor product. PMID- 11194130 TI - Triple-drug tablet approved for HIV infection. PMID- 11194131 TI - Merck-Medco offers free generics to physicians. PMID- 11194132 TI - AHRQ assesses evidence for best management of COPD exacerbations. PMID- 11194133 TI - Opposing groups find common ground on health care coverage. PMID- 11194134 TI - Pharmacy and the e-train: time to get on board. PMID- 11194135 TI - Treatment strategies for recurrent oral aphthous ulcers. AB - The clinical features, etiology, and treatment of recurrent aphthous ulcers (RAU) are discussed. Aphthous ulcers are among the most common oral lesions in the general population, with a frequency of up to 25% and three-month recurrence rates as high as 50%. The ulcers, which usually occur on the nonkeratinized oral mucosa, can cause considerable pain and may interfere with eating, speaking, and swallowing. RAU is classified as minor, major, and herpetiform on the basis of ulcer size and number. The cause of RAU is idiopathic in most patients. The most likely precipitating factors are local trauma and stress. Other associated factors include systemic diseases and nutritional deficiencies, food allergies, genetic predisposition, immune disorders, the use of certain medications, and HIV infection. The primary goals of therapy for RAU are relief of pain, reduction of ulcer duration, and restoration of normal oral function. Secondary goals include reduction in the frequency and severity of recurrences and maintenance of remission. Topical medications, such as antimicrobial mouthwashes and topical corticosteroids, can achieve the primary goals but have not been shown to alter recurrence or remission rates. Systemic medications can be tried if topical therapy is ineffective. Levamisole has shown variable efficacy in reducing ulcer frequency and duration in patients with minor RAU. Oral corticosteroids should be reserved for severe cases of major RAU that do not respond to topical agents. Thalidomide is effective but, because of its toxicity and cost, should be used only as an alternative to oral corticosteroids. RAU can be effectively managed with a variety of topical and systemic medications. PMID- 11194136 TI - Validity and reliability of observational methods for studying medication administration errors. AB - The validity and reliability of observational methods for studying medication administration errors (MAEs) were studied. Between January and June 1998, two pharmacists observed consecutive drug administration rounds by nurses on two wards in a U.K. hospital and recorded all MAEs identified. The observers intervened in cases of potentially harmful errors. MAE records were audited to determine the percentage of omitted doses for which a corresponding reason was documented for the observation periods and for nonobservation periods. Error rates for each drug administration round were analyzed according to whether they were for the nurse's first, second, third (and so on) observed round. Error rates were calculated before and after the first intervention with nurses for whom an intervention was made. Observer reliability was calculated by comparing the rates of errors identified by the two observers. There was no difference between the observation and nonobservation periods in the percentage of omitted doses for which a reason was documented, and there was no change in the error rate with repeated observations. There was no difference in error rates before and after the first intervention for each nurse. There was also no difference in error detection between the two observers and no change with increasing duration of observation. Observation of nurses during drug administration at a U.K. hospital did not significantly affect the MAE rate; nor did tactful interventions by the observers. Observer reliability was high. Concerns about the validity and reliability of observational methods for identifying MAEs may be unfounded. PMID- 11194137 TI - The Institute of Medicine report on medical error: overview and implications for pharmacy. PMID- 11194138 TI - Pharmacists building a safer health system. PMID- 11194139 TI - Credentialing in pharmacy. The Council on Credentialing in Pharmacy. PMID- 11194140 TI - Centralized, pharmacist-managed anticoagulation service for a university-based health system. PMID- 11194141 TI - Of medication orders and deli sandwiches. PMID- 11194142 TI - Additional Novartis products available through assistance programs. PMID- 11194143 TI - Human tooth enamel as a record of the comparative lead exposure of prehistoric and modern people. AB - There is a considerable body of evidence to support the contention that the atmospheric Pb burden is now considerably greater than it was in the remote past. However, as there are a diversity of potential environmental pathways leading to Pb ingestion, it is not clear how atmospheric Pb levels relate to human exposure. It is necessary to establish a baseline for human exposure to Pb from natural sources in the pre-metallurgical past, with which contemporary exposure can be compared. This paper addresses this issue by comparing the Pb content of human dental enamel--an established proxy for Pb exposure--from modern and archaeological, pre-metallurgical individuals using thermal and plasma ionisation mass spectrometry. It is shown that mean Neolithic enamel Pb contents are approximately 0.31 +/- 0.04 ppm. These values are only one order of magnitude lower than previously reported data for the same tissues for modern juveniles, despite an established 400-fold increase in the atmospheric Pb burden. The results suggest that 'natural' exposure to Pb in food and water may have been higher than previously thought, and that the link between atmospheric Pb and human exposure warrants further investigation. PMID- 11194144 TI - Characterization of visibility and atmospheric aerosols in urban, suburban, and remote areas. AB - Visibility data from over the past four decades accumulated from urban areas of central Taiwan indicated that air pollutants have significantly degraded visibility in recent years. Currently, the annual average visibility in urban areas of the same region is approximately 8-10 km, while the visibility in remote areas is approximately 25-30 km. To understand how aerosols affect the visibility in this region, here we selected three sites in central Taiwan to measure the soluble ionic and carbonaceous species of PM(2.5) and PM(2.5-10) during 1997 1998. A MOUDI cascade impactor was used to measure the size distributions of atmospheric sulfate, nitrate, and carbonaceous particles. The aerosol data were then analyzed together with meteorological and air quality data. Comparing the results obtained from urban, coastal suburban and remote sites revealed that sulfate, carbonaceous species and local wind speed significantly affected the visibility in the urban area. However, sulfate concentration and humidity influenced visibility in the coastal area of central Taiwan. The particulate concentration at the remote station was roughly one-fifth of that in the city. Regression analysis results indicated that humidity is a dominant factor affecting remote visibility. PMID- 11194145 TI - Study of the copper distribution in contaminated soils of hop fields by single and sequential extraction procedures. AB - Hop growing in Bavaria requires the use of copper containing fungicides against mildew, which results in an accumulation of copper in the upper soils to concentrations of up to approximately 450 mg kg(-1). The naturally occurring concentration of copper is approximately 10-15 times lower. Several single and sequential extractions were performed in parallel to the determination of total copper content after aqua regia digestion. By these means copper mobility and retention, its availability to plants as well as its distribution in soils was assessed. Three agricultural soils and two soils from fallow land have been analysed to elucidate whether the copper distribution changes in relation to agricultural activities and to predict environmental risks due to the high copper concentrations. This work also focuses on the difficulties arising from different results when using single and sequential extraction procedures. EDTA, acetic acid, deionised water, ammonium nitrate and calcium chloride were used as single extractants for the functionally defined speciation. EDTA and acetic acid can be regarded as extractants for the plant-available species, while deionised water, NH4NO3 and CaCl2 only release electrostatically weakly bound metals to estimate the mobile species. The extraction behaviour of copper in these procedures is discussed with respect to the quantities extracted from the contaminated and non contaminated soils. The studies indicate that no vertical copper translocation is observed in the ground, but the main amounts are highly available to plants. Sequential extraction procedures were used for operationally defined speciation, quantifying copper in specific soil phases. The 'five-step extraction scheme' first applied, suggested by the Standard Measurement and Testing Programme of the European Community, overestimated the amounts of copper bound to the residual phase. This was mainly due to the non-specific nature of the reagents for the organic/sulfidic and crystalline iron oxide fraction. A second reason could be the fact that this scheme was developed for sediment and not for soil analysis. Therefore, the sequential extraction has been applied using an adapted method of Zeien and Bruemmer, using different extractants for the two phases. The copper distribution was different, showing that approximately 40-50% of the total copper was bound to the organic fraction and approximately 15-30% could be extracted with the iron oxides. The amounts in the residual fraction were much lower. After comparing the results of the different extraction procedures the environmental behaviour of copper and its risks for plants, micro-organisms and groundwater is discussed in brief. PMID- 11194146 TI - Adsorption equilibriums of principal herbicides on paddy soils in Japan. AB - Herbicides used in paddy fields during the flooding season can easily cause pollution by run-off into rivers or by other routes. It is very important to know the adsorption characteristics that influence their fate in the soil. The adsorption equilibriums have often been expressed by Henry equations, and the values of equilibrium constant, Kd, are estimated from the adsorption constants, K(OC), based on organic carbon contents of soils. There is little information concerning the equilibrium values expressed by the Freundlich equations, and insufficient information on the actual concentration levels in the paddy field. Therefore, adsorption equilibriums of the five principal herbicides: esprocarb, mefenacet, pretilachlor, simetryn and thiobencarb, on five kinds of paddy soil in Japan were investigated. It was found that their equilibrium values were better expressed by the Freundlich equation for concentration levels for the paddy fields, and that the values for the adsorption coefficient, n, varied from 1.0 to 1.6. Values for the coefficient, k, were in the range of 29-420 mg(1 - 1/n) l(1/n)/kg-dry, and the values were poorly related to solubilities in water or to the octanol-water partition coefficients of the herbicides. For each herbicide, except for simetryn, the values of k among the soils differed by 2-3 times, and no correlation could be found with the organic carbon contents, specific surface areas, pH, cation exchange capacity or major minerals of the soils. The adsorption equilibriums calculated from the values of adsorption constant Kd by the values of K(OC) in the literature were found to be very different from the experimental equilibriums. From the experimental values of coefficient k and n of the Freundlich equation, the maximum runoff concentrations of the herbicides were preliminarily estimated by a simple equilibrium model. PMID- 11194147 TI - Selenium and iodine in soil, rice and drinking water in relation to endemic goitre in Sri Lanka. AB - Endemic goitre has been reported in the climatic wet zone of south-west Sri Lanka for the past 50 years, but rarely occurs in the northern dry zone. Despite government-sponsored iodised salt programmes, endemic goitre is still prevalent. In recent years, it has been suggested that Se deficiency may be an important factor in the onset of goitre and other iodine deficiency disorders (IDD). Prior to the present study, environmental concentrations of Se in Sri Lanka and the possible relationships between Se deficiency and endemic goitre had not been investigated. During the present study, chemical differences in the environment (measured in soil, rice and drinking water) and the Se-status of the human population (demonstrated by hair samples from women) were determined for 15 villages. The villages were characterised by low (< 10%), moderate (10-25%) and high (> 25%) goitre incidence (NIDD, MIDD and HIDD, respectively). Results show that concentrations of soil total Se and iodine are highest in the HIDD villages, however, the soil clay and organic matter content appear to inhibit the bioavailability of these elements. Concentrations of iodine in rice are low (< or = 58 ng/g) and rice does not provide a significant source of iodine in the Sri Lankan diet. High concentrations of iodine (up to 84 microg/l) in drinking water in the dry zone may, in part, explain why goitre is uncommon in this area. This study has shown for the first time that significant proportions of the Sri Lankan female population may be Se deficient (24, 24 and 40% in the NIDD, MIDD and HIDD villages, respectively). Although Se deficiency is not restricted to areas where goitre is prevalent, a combination of iodine and Se deficiency could be involved in the pathogenesis of goitre in Sri Lanka. The distribution of red rice cultivation in Sri Lanka is coincident with the HIDD villages. Varieties of red rice grown in other countries contain anthocyanins and procyanidins, compounds which in other foodstuffs are known goitrogens. The potential goitrogenic properties of red rice in Sri Lanka are presently unknown and require further investigation. It is likely that the incidence of goitre in Sri Lanka is multi factorial, involving trace element deficiencies and other factors such as poor nutrition and goitrogens in foodstuffs. PMID- 11194148 TI - Baseline metal concentration in the Asian periwinkle Littorina brevicula employed as a biomonitor to assess metal pollution in Korean coastal water. AB - Concentrations of Al, Fe, Mn, Cu, Zn, V, Ni, Co, Cr, Cd and Pb in the Asian periwinkle Littorina brevicula were determined from 39 sampling locations along the whole Korean coast. Metal concentrations in the periwinkle varied highly with sampling stations, but the variations could be well explained by the body size after eliminating the data exceeding the 'High' criteria. Among the stations exceeding the 'High' criteria corresponding to mean plus one standard deviation of the logarithms of the individual site mean, some stations exhibited values higher than expected from the relationship between metal body burden and body size, indicating that these locations were polluted with metals. However, several 'High' stations followed the trends of the curve, suggesting that they resulted from the effect of their small body size, not from environmental contamination. Periwinkles of similar body sizes exhibited same range of metal concentrations in their body, independent of geographical position. PMID- 11194149 TI - The measurement of volatile constituents in Foray 48B, an insecticide prepared from Bacillus thuringiensis var. kurstaki. AB - Foray 48B, an insecticide prepared from Bacillus thuringiensis var. kurstaki (Btk), has been used for many years to combat infestations of Gypsy moths. Foray 48B also contains a large number of 'inert ingredients' which are not disclosed by the manufacturer. Gypsy moths usually enter the country through marine- and airports in close proximity to urban areas, which consequently need to be sprayed. The population affected often demands more detailed information than what is available including the potential presence of volatile organic agents which could be released during spraying, posing a potential health hazard. Four different methods were investigated using GC/mass spectrometry regarding their ability to capture volatile agents associated with Foray 48B. It was found that solid phase micro-extraction was most efficient in capturing volatile agents from the head-space of Foray 48B. Separate trials using 95:5% ethanol/isopropanol mixture and toluene in an impinger configuration were much less efficient. Standard techniques using activated charcoal tubes in the laboratory setting as well as in a field trial did not capture any compounds. It was concluded that the volatile agents associated with Foray 48B did not appear to constitute a significant health hazard and no one agent was a likely candidate to serve as a tracer for Foray 48B exposure. PMID- 11194150 TI - Quantitative assessment of estrogenic activity in the water environment of Korea by the E-SCREEN assay. AB - In this study, the E-SCREEN assay was optimized and validated for the sensitive quantitative determination of the total estrogenicity in river samples. River water and sediment samples were collected and analyzed with the E-SCREEN. River water (10 l) was extracted using combined solid-phase extraction in static adsorption mode with Soxhlet extraction. Estrogenic pollutants adsorbed to the XAD-4 resin were recovered with 98.24 +/- 5.90% efficiency by elution with ethyl acetate and dichloromethane (1:9). The detection limit by 17beta-estradiol equivalent concentration (EEQ) of the E-SCREEN assay was 8.03 pg EEQ/l. Among the water samples, the estrogenic activity was observed to be higher downstream of the Kumho river (7.43 ng EEQ/l) and upstream of Kum river (2.05 ng EEQ/l) than in other samples. More than 3 mg of equivalent sediment samples from the Kumho river, Kum river and Miho stream showed partial agonistic effects, and the Mankyung river showed a partial agonistic effect with only 1.5 mg of sediment. The highest value of RPE was 83.34 downstream of the Kumho river, and the lowest value of RPE was 6.52 downstream of the Miho stream. Full estrogen agonistic activities were observed downstream of the Kumho river and upstream of the Kum river. The partial agonistic activity was observed in upstream of the Kumho river, downstream of the Mankyung river, and upstream of the Miho stream, and no agonistic action was observed downstream of the Kum river or Miho stream, or upstream of the Mankyung river. The total estrogenic activity in the river water and sediment samples was between 0.50 pg/L and 7.4 ng/L, 3.39 pg/g and 10.70 pg/g. PMID- 11194151 TI - Determination of radionuclide exchangeability in freshwater systems. AB - Two freshwater sediments were spiked with 57Co, 85Sr and 134Cs and left for adsorption times ranging from 1 day to over 60 days. Following adsorption, the 'exchangeable' pool of each radionuclide was measured using ammonium acetate extractions and a sequential leach procedure (Tessier et al., 1979), and the results were compared. Exchangeability was found to depend upon the sediment, radionuclide, sorption time and the identity of extracting agent. All three radionuclides showed a shift with increasing adsorption time from regular exchange sites to sites which are sterically hindered, but a fixation within the sediment was only observed for 57Co and 134Cs, with similar ammonium acetate extraction yields for both radionuclides. Misleading results were obtained during the sequential leach procedure due to redistribution and, therefore, the inclusion of a NH4+ leach after the MgCl2 extraction step was suggested. A mathematical model of element speciation was fairly successful at defining the 'exchangeable' fraction, suggesting that the chemically- and mathematically defined fractions were similar. PMID- 11194152 TI - Algal biomass in a disturbed Atlantic river: water quality relationships and environmental implications. AB - Benthic algal biomass was determined at 38 sites along the Oria, a river with intense human activity on its watershed. Water temperature, total suspended solids and nutrient concentration affected algal biomass in different ways. Lower values of algal biomass [(chlorophyll-a concentration and ash-free dry weight (AFDW)] were found in the headwaters and forested tributaries, but also at sites receiving high deposition of solids (due to the outflow from paper mills and quarries). Higher values of algal biomass (both chlorophyll-a and AFDW) were common both in the main stretch of the river and in some tributaries receiving urban sewage outflows. Averages and ranges of temperature and dissolved oxygen concentration were compared for two continuously monitored stations. One of them (forested, nutrient-poor) had low algal biomass, while the second (open, nutrient rich) showed high chlorophyll-a concentration. Accumulation of algal biomass had environmental implications both in water quality and in the fish diversity of the Oria. Diel variations of dissolved oxygen were much higher (and reached hypoxia) at the site with higher biomass accumulation. The abundance of a fish community (dominated by cyprinids) more tolerant to hypoxia at that site can partly be attributed to the influence of algal biomass accumulation. PMID- 11194153 TI - Serum concentrations of organochlorines in men: a search for markers of exposure. AB - Analysis of single marker substances in serum could provide cost-effective assessment of human exposure to complex mixtures of organochlorines. We studied the serum concentrations of 10 polychlorinated biphenyl (PCB) congeners and 11 chlorinated pesticides and some of their metabolites in samples collected from 120 Swedish men (mean age 63 years, range 40-74 years) from the general Swedish population. The median concentrations of individual PCB congeners increased in the order PCB 52 < PCB 101 < or = PCB28 < PCB 105 < PCB 167 < PCB 156 < PCB 118 < PCB 138 < PCB 180 < PCB 153. The concentrations of o,p'-DDT, o,p'-DDE, p,p'-DDD, alpha-HCH and gamma-HCH were in most cases below the quantification limit (2-4 ng/g lipid). Among the other chlorinated pesticides the median concentration increased in the order oxychlordane (12 ng/g lipid) < p,p'-DDT < trans-nonachlor < beta-HCH < HCB < p,p'-DDE (586 ng/g lipid). The observed concentrations of PCB and chlorinated pesticides were in the same range as those found in similar groups of men from Sweden and Norway, but lower than those found in male populations with recent occupational exposure or high environmental exposure. Strong relationships were found between the concentrations of single mono- and di ortho PCB congeners and groups of PCB congeners in serum. In our group of men PCB 153 was a good marker substance for the concentration of sigma PCB and sigma di ortho PCB concentrations in serum. Moreover, among the mono-ortho PCB congeners analyzed, PCB 156 could be used as a marker for the sigma mono-ortho PCB TEQ concentrations in serum in the studied group. No useful marker substances were found among DDT compounds and other chlorinated pesticides and metabolites, except for trans-nonachlor which predicted the concentration of the metabolite oxychlordane fairly well. PMID- 11194154 TI - Minerals controlling arsenic and lead solubility in an abandoned gold mine tailings. AB - Numerous areas have been contaminated by heavy metals and metalloids due to industrial and mining activities. Studies investigating the behavior of such contaminants in the environment have identified speciation as a key factor controlling their mobility, availability and toxicity. Here we characterize As- and Pb-bearing phases resulting from the oxidation of sulfide-rich tailings of a former gold mine (La Petite Faye, France) in order to assess the risk for water quality. Elements were first pre-concentrated by granulometric fractionation (sedimentation in deionized water) and then investigated using X-ray diffraction and electron microprobe analyses. Two main As-Pb-bearing minerals were clearly identified: scorodite (FeAsO4 x 2H2O) and beudantite PbFe3(AsO4)(SO4)(OH)6. Minor amounts of As and Pb were dissolved in deionized water during granulometric fractionation, indicating the possible presence of other soluble Pb-sulfates which could be some of the primary metastable products of sulfide oxidation. This dissolution also provides information about the fate of these phases in the case of intensive leaching of the tailings. Scorodite may not be considered as a relevant candidate for As on-site immobilization, because its solubility largely exceeds drinking water standards whatever the pH. Since beudantite solubility has not yet been determined, an estimation of its solubility product was obtained using the Gibbs free energy of formation of plumbojarosite [Pb0.5Fe3(SO4)2(OH)6]. This estimation suggests that beudantite should efficiently maintain low Pb concentration in waters. However, Pb dissolution in deionized water during the granulometric fractionation led to Pb concentrations much higher than the French and US drinking water standards (2.4 x 10(-7) mol l(-1)), which may be due to dissolution of the suspected metastable Pb-sulfates. Accurate determination of beudantite solubility is now required to improve the Pb risk assessment on such polluted sites. PMID- 11194155 TI - Determination of metals in plant samples by using a sector field inductively coupled plasma mass spectrometer. AB - The capability of pine needles to be used as bioindicators of trace metals in the environment is discussed. Samples were collected around the Instituto de Pesquisas Energeticas e Nucleares, the largest nuclear research center in South America and chosen to be the sampling target area. Results obtained for the elemental content of Th and U in samples collected nearby an uranium facility were, respectively, 0.072 and 0.042 mg kg(-1), while the results obtained for the La, Ce and Sm content in a sample collected in the vicinity of an extraction laboratory were, respectively, 0.22, 0.88 and 0.39 mg kg(-1). All these values are higher than the ones obtained with a reference sample (La 0.12; Ce 0.19, Th 0.020 and U 0.012 mg kg(-1)), located far from the target area. Internal standardization was used to compensate the non-spectral interference of the different elements present in the sample solution matrix. The chemical elements bismuth (Bi) and indium (In) were chosen as internal standards. In order to control the accuracy of the chemical measurement process, certified samples of pine needles (NBS SRM 1575) were also analyzed. The results obtained show the capability of the investigated method in the determination of the relevant trace metals in the environment. PMID- 11194156 TI - The effect of surface coatings on the association of orthophosphate with natural colloids. AB - A new method has been utilised for the characterisation of natural particle surface coatings. The method involves the use of sedimentation field-flow fractionation (SdFFF), radiolabelling and inductively coupled plasma-high resolution mass spectrometry (ICP-HR MS) techniques to study the effect of colloidal surface coatings on the adsorptive behaviour of orthophosphate. Colloidal river sediment and soil samples were chemically treated in an attempt to selectively remove metal hydroxyoxides and natural organic matter. The samples were then radiolabelled with 33PO4(3-) and analysed by SdFFF to determine the surface adsorption density (SAD) of orthophosphate as a function of particle size. The SdFFF unit was directly coupled to an ICP-HR MS to determine the chemical composition of the colloidal samples as a function of particle size. Element concentration/UV detector signal and element atomic molar ratios were plotted against particle size, and the trends used in the interpretation of SAD distribution (SADD) changes for the samples were studied. In general, non constant trends in the orthophosphate SADDs were found, except for the river sediment treated with hydroxylamine hydrochloride. The results indicated that, in the soil sample studied, the Mn oxide coating was a dominant factor in determining phosphorus adsorption. This method could also be applicable to other industrial or similar samples. PMID- 11194157 TI - 16-year trends in elements of lichens at Theodore Roosevelt National Park, North Dakota. AB - An epiphytic lichen and a soil lichen in two very closely related genera (Parmelia sulcata and Xanthoparmelia chlorochroa, respectively) were sampled 16 years apart at Theodore Roosevelt National Park in North Dakota and measured for their elemental content. Mercury and cadmium decreased approximately 30% over the time period in both species. Sulfur decreased 8% in the epiphytic species, but increased 20% in the soil lichen. Factor analysis revealed that soil elements were higher in the soil lichen, indicating there was some soil contamination in that species. A relationship between iron and titanium was found only in the soil lichen. Sulfur and mercury were highly enriched in both species relative to the soil, which suggests that the atmosphere is a contributing source of these elements. New baseline values were calculated, 22 elements for both species, although it is not recommended that the soil lichen be sampled in the future. PMID- 11194158 TI - Methane emission from a simulated rice field ecosystem as influenced by hydroquinone and dicyandiamide. AB - A simple apparatus for collecting methane emission from a simulated rice field ecosystem was formed. With no wheat straw powder amended all treatments with inhibitor(s) had so much lower methane emission during rice growth than the treatment with urea alone (control), which was contrary to methane emission from the cut rice-soil system. Especially for treatments with dicyandiamide (DCD) and with DCD plus hydroquinone (HQ), the total amount of methane emission from the soil system and intact rice-soil system was 68.25-46.64% and 46.89-41.78% of the control, respectively. Hence, DCD, especially in combination with HQ, not only increased methane oxidation in the floodwater-soil interface following application of urea, but also significantly enhanced methane oxidation in rice root rhizosphere, particularly from its tillering to booting stage. Wheat straw powder incorporated into flooded surface layer soil significantly weakened the above-mentioned simulating effects. Regression analysis indicated that methane emission from the rice field ecosystem was related to the turnover of ammonium-N in flooded surface layer soil. Diminishing methane emissions from the rice field ecosystem was significantly beneficial to the growth of rice. PMID- 11194159 TI - Ecological half-life of 137Cs in fish from a stream contaminated by nuclear reactor effluents. AB - Radiocesium (137Cs) concentrations were determined during 1974, 1981 and 1998 for seven species of fish inhabiting a stream (Steel Creek) contaminated by effluents from a nuclear reactor to examine the decline of this radionuclide in a natural ecosystem. Median 137Cs concentrations were highest in Micropterus salmoides (largemouth bass) during each year of the investigation (1974 = 6.67 Bq g(-1) dry wt. of whole body; 1981 = 3.72 Bq g(-1); 1998 = 0.35 Bq g(-1)), but no patterns of differences were observed among Aphredoderus sayanus (pirate perch), Esox americanus (redfin pickerel), Lepomis auritus (redbreast sunfish), L. gulosus (warmouth), L. punctatus (spotted sunfish), and Notropis cummingsae (dusky shiner). Results demonstrated a rapid decline in 137Cs within fish from Steel Creek during the 24-year period. For example, 137Cs concentrations in all fish species declined significantly among years, even after accounting for radioactive decay. The observed percent declines in 137Cs concentrations of individual species were 3-4 times greater between 1974 and 1981 compared to that expected by physical decay alone, and 2-3 times greater during 1981-1998. Ecological half lives (EHLs) of 137Cs in fish ranged from 4.43 years in A. sayanus to 6.53 years in L. gulosus. The EHL for 137Cs in all fish species combined was 5.54 years. Current levels of 137Cs in fish from Steel Creek (1.16 Bq g(-1) dry wt. of whole body to below detection limits) indicate that the consumption of fish from this ecosystem poses little risk to humans and sensitive wildlife species. These results demonstrate the importance of incorporating the concept of ecological half-life into determinations concerning the length and severity of potential risks associated with radiocontaminants. PMID- 11194160 TI - Comparison of atmospheric pesticide concentrations measured at three sampling sites: local, regional and long-range transport. AB - We present the comparison of atmospheric concentrations of eleven currently used pesticides (HCB, alpha-HCH, gamma-HCH, trifluraline, mecoprop, phosalone, atrazine, carbofuran, carbaryl, diuron and isoproturon) measured in remote (Aubure), rural (Colmar) and urban (Strasbourg) areas of Alsace and Vosges regions (cast France). Pesticides samples were collected simultaneously on two of the three sites during the summer season of 1993 and 1994, using a Hi-Vol sampler with Whatman filter paper and XAD-2 resin. The particle and gas phases were collected separately during 24 h. The relative importance of local emissions and local, regional and long distance transport on the contamination of the atmosphere in the three environments (remote, rural and urban) were investigated. To facilitate the interpretation of the results, the alpha/gamma-HCH ratio was used as a tracer of pesticide emissions. PMID- 11194161 TI - The long-term evolutions and the regional characteristics of atmospheric methane concentrations in Nagoya, 1983-1997. AB - This study provides information on the long-term evolutions of the atmospheric methane (CH4) concentrations in Nagoya City, Japan, which were analyzed by using the continuous monitoring data observed at the eight observatory stations for 1983-1997. The 15-year records of the atmospheric CH4 concentrations were examined by means of a time-series analysis using a fast Fourier transform with a low-pass filter to elucidate the seasonal cycles and the long-term trends. The annual averages of the CH4 concentrations in Nagoya were 1.85 ppmv (parts per million by volume), 1.91 ppmv, and 1.90 ppmv in 1988, 1995 and 1997, respectively. Moreover, the annual average growth rate showed a drastic decrease from 17 ppbv (parts per billion by volume) year(-1) in 1992 to 2 ppbv year(-1) in 1993, and further down to 7 ppbv year(-1) in 1997. Comparison of the atmospheric CH4 records in Nagoya with those in global air of the northern hemisphere observed at Mauna Loa observatory in Hawaii, USA, allows us to estimate the excess concentration of CH4 in the urban atmosphere of Nagoya, which was 0.17 ppmv in 1988 and 0.15 ppmv in 1997. On a local scale, the atmospheric CH4 concentrations in the northern part of Nagoya City increased until 1992 and then gradually decreased from 1993 to 1997, although those in the south-western urban areas constantly increased at the averaged growth rate of 13 ppbv year(-1) for 1988-1997. The variation of the long-term trends of the CH4 concentrations in Nagoya may be ascribed to the emission changes from the CH4 sources due to the human activities such as waste dumping and landfills. PMID- 11194162 TI - Feasibility of assessing dermal exposure to PAHs of workers on gaswork sites--the SOLEX study. AB - Population exposure to pollutants in soil is an important public health concern. Difficult to measure, it is usually estimated using multimedia models. Modeling data predict that the skin surface is a predominant exposure route in roughly 15% of the US Superfund sites. Nonetheless, no study has confirmed these predictions. The SOLEX study was an opportunity to study the feasibility of estimating the cutaneous polycyclic aromatic hydrocarbons (PAHs: all 16 of the United States Environmental Protection Agency list) load of workers at three former manufactured gas sites, one of those being under remediation. Over two measurement periods (November 1997 and June 1998), 30 and 28 volunteers, respectively, were equipped for a single day work with five pads that collected soil particles and were placed at the neck, shoulder, wrist, groin, and ankle. Pad contamination was observed for six of the nine workers on the site being remediated but not on other sites. The wrist pad was most often affected, followed by the neck pad, these are, the exposed regions of the body. The PAHs most frequently identified were anthracene, fluoranthene, naphthalene, phenanthrene, and pyrene, at concentrations relatively high. In conclusion, this study showed that estimating skin exposure to soil pollutants is feasible. Secondly, it suggested that only subjects in close contact with the soil had a detectable exposure to PAHs. Extension of this approach to other exposure settings is warranted, especially among children playing in polluted public or private gardens, because their games lead to frequent contact with the soil. PMID- 11194163 TI - Seasonal and long-term variation of 210Pb concentration in air, atmospheric deposition rate and total deposition velocity in south Germany. AB - The activity concentration in air and atmospheric deposition rate of the long lived radon progeny 210Pb has been investigated at Munich-Neuherberg, south Germany, from 1972 (activity concentration) and from 1981 (atmospheric flux) to 1999. For these periods, the continuous measurements yielded an average 210Pb activity concentration at ground level of 0.57 mBq m(-3) and an average total 210Pb deposition rate to ground of 180 Bq m(-2) year(-1). The average total deposition velocity, which relates the total 210Pb deposition rate to the 210Pb activity concentration was calculated to be 1.0 cm s(-1). The variation of the data with time was studied by time-series analysis and distinct seasonal patterns were identified. Maximum 210Pb activity concentrations in air are observed in the autumn and winter months (October through February) of each year. By contrast, the maximum 210Pb deposition rate is observed during summer (June-August), i.e. in the months with the highest amount of rainfall at this site. Like the 210Pb deposition rate, the total deposition velocity exhibits a seasonal pattern with maximum values in summer. Due to the long observation period of 18 years, it was possible to observe for the first time a strong positive relationship between 210Pb deposition and precipitation, especially for the months May and June and to a smaller extent for several other months. In the long-term, variations of approximately a factor of 2 were observed in the annual average 210Pb activity concentrations, the annual deposition sums and the annual average deposition velocities. Since around 1981 210Pb concentrations in air steadily decreased while 210Pb depositions increased. As a consequence of these significant trends, the time series of the total deposition velocity exhibits a trend of the data from approximately 0.7 cm s(-1) in 1981 to 1.7 cm s(-1) in 1999. PMID- 11194164 TI - Granulometry and the content of toxic and potentially toxic elements in vacuum cleaner collected, indoor dusts of the city of Warsaw. AB - Twenty-seven sites, together with 23 household dust sample sites, representing the home environment, and four public room dust sample sites, representing working environment (mainly offices) have been described in this paper. The latter were examined to obtain an approximate reference to the home environment data. All the samples were collected between May and July 1997 by a vacuum cleaner method, in the city of Warsaw, Poland. The granulometry of the dusts was determined by their separation into seven fractions in the range 8-500 microm. The concentrations of Cr, Ni, Cu, Zn, Pb, Br and Fe in the samples were investigated in fractions 8-32, 32-63 and 63-125 microm by the EDXRF technique. The results showed higher concentrations of these elements in finer fractions (8 32 microm). The Pb content in the household dusts was found to be unexpectedly low, ranging from 120 microg g(-1) for the 63-125 microm fraction, up to 210 microg g(-1) for the 8-32 microm fraction. Car exhausts could not be determined clearly as the main source of Pb in the indoor household dusts due to the lack of a Pb-Br intercorrelation. In these dusts, only Cr and Zn showed a remarkably high content of 90-100 and 1020-1070 (microg g(-1)), respectively. In the household dusts, strong intercorrelations were present in the three analysed fractions for the metal pairs: Pb-Zn, Pb-Cu, Fe-Cr, and Cu-Cr (weaker). The working environment rooms showed a higher degree of dustiness by 300%, as compared to the dwellings. The dusts collected in the working environment rooms showed slightly higher concentrations of Ni and by 50-100% higher concentrations of: Cu, Zn, Pb, Br than the analysed household dusts. PMID- 11194165 TI - Human impact on the environment in Japan and New Zealand: a comparison. AB - Because of its proximity to Asia, Japan has been populated by humans for a much longer time period than New Zealand and has a much higher population density. The similarity in geology and tectonic setting of the two island groups has forced both peoples to confront similar environmental hazards but this was achieved in different ways. During the Edo period (1600-1868) when contact with outside countries was limited, the Japanese adapted their agricultural practices to the environment and developed an agricultural system that corresponds closely to the ideals of sustainability. Indeed, it can be argued that the farming lifestyle of the Edo period was the most advanced way of life that can be adopted without depleting stock resources. Following the Meiji restoration in 1868, the policy of rapid industrialization led to many environmental mistakes, particularly after World War II. By the end of the 1960s, Japan was the world's most polluted country. The situation has subsequently improved greatly from this low point but much remains to be done. New Zealand was initially occupied by the Maori over 1000 years ago. They did more environmental damage than was previously thought, particularly in burning off bush and destroying the bird life. However, it was the colonization of New Zealand by the Europeans after 1840 that led to the greatest environmental damage with their introduction of farming methods unsuited to the conditions. Although the need for better scientific planning of land use practices within New Zealand is recognized, sustainable management of the environment remains a distant goal. More detailed study of the agricultural methods and lifestyles adopted in Japan during the Edo period could help in defining the concept of sustainability. PMID- 11194166 TI - Polycyclic aromatic hydrocarbons in soil and plant samples from the vicinity of an oil refinery. AB - Soil samples, and samples of leaves of Plantago major (great plantain) and grass (mixed species) were collected from the vicinity of an oil refinery in Zelzate, Belgium, and analysed for seven polycyclic aromatic hydrocarbons (PAHs). The samples from the site adjacent to the refinery (site 1) contained very high total PAH-concentrations: namely 300, 8 and 2 microg/g dry wt. for soil, P. major and grass, respectively. Concentrations in samples from more remote sites (up to 4 km from the refinery) were a factor of 10-30 lower than those from site 1, but between them the differences were small. The PAH-profiles of the plant samples, in contrast with those of the soil samples, appeared to shift to higher contributions of gaseous PAHs with increasing distance from the refinery. This can be explained by particle-bound PAHs being deposited closer to the source than gaseous PAHs. It is suggested that particle-bound deposition is relatively more important for deposition to soil than to plants, due to blow-off and wash-off of the compounds from the leaves. The total PAH-concentrations in the leaves of P. major were higher than those measured in the grass samples, probably due to differences in aerodynamic surface roughness, leaf orientation and/or leaf age. However, the concentration ratios of P. major/grass were not constant for the different sites, varying from 1.2 to 8.8. Therefore, it appears that a precise prediction of PAH-concentrations for one plant species from known concentrations of another species is not possible. When errors in predicted concentrations need to be smaller than a factor of approximately 10, the sampling strategy has to be focussed on all species of interest. PMID- 11194167 TI - Population-based planning a popular tool for ASCs (ambulatory surgery centers). PMID- 11194168 TI - AMA launches partnership to lease physician database. AB - A joint venture is allowing the AMA to refine the physician data it sells to marketers. Physicians in the organization's heavily used database get some latitude in how information about them is distributed. PMID- 11194169 TI - Physicians go online for electronic medical records. AB - Frustrated with electronic health records systems on the market, a California physician took matters into his own hands. The result is an electronic medical records system in use by 9,000 physicians in about a dozen communities. PMID- 11194170 TI - Medical school consortium develops clinical protocols using Web-based strategy. PMID- 11194171 TI - HCIA-Sachs benchmarking study. Top-performing orthopedic hospitals have better outcomes despite higher acuity. PMID- 11194172 TI - Pharmacodynamic study of Hypericum perforatum L. AB - The effects of Hypericum perforatum L. (Hypericaceae) crude ethanol extract (A), ethyl acetate extract (B), aqueous extract (C) and infusion (I), on pentobarbital induced sleeping time, intestinal motility, and their analgesic activity, have been investigated. Extracts A and B exhibited significant stimulatory and antidepressant effects on the CNS. Both extracts prolonged sleep, increasing time up to more than 25 min. The antidepressive activity of extract A was also achieved by significant reduction of the myorelaxant activity of diazepam. Extract B exhibited strong analgesic activity reducing abdominal stretching induced by acetic acid by nearly 50 %. Extracts A, B and C exhibited spasmolytic activity, significantly reducing intestine motility. PMID- 11194173 TI - Oral bioavailability of active principles from herbal products in humans. A study on Hypericum perforatum extracts using the soft gelatin capsule technology. AB - The oral absorption of two known active principles of Hypericum perforatum, namely hyperforin and hypericin, was studied in an open, single dose, two-way, randomized, cross-over study involving 12 healthy subjects (six males and six females). Alcoholic Hypericum extract (300 mg, containing 5% hyperforin and 0.3 % hypericin) was administered in the morning after 12 hours fasting. The formulation was administered as softgel capsules containing, inter alia, soya oil together with the herbal extract. A second standard formulation in two piece hard gelatin capsules was also used for comparison purposes. Blood was sampled from the subjects at different times after drug administration and the plasma was analysed according to published analytical methods for the determination of hyperforin and hypericin. Peaks of plasma concentration, Cmax of hyperforin were 168.35 ng/ml +/- 57.79 for the soft gelatin formulation (CV=34.32, n=12) and 84.25 ng/ml +/- 33.51 for the hard gelatin capsule (CV=39.77, n=12). The Tmax values for hyperforin were 2.50 h +/- 0.83 for the soft gelatin formulation compared to 3.08 h +/- 0.79 for the reference formulation, whereas the total AUC were respectively 1482.7 h x ng/ml +/- 897.13 and 583.65 h x ng/ml +/- 240.29. As for hypericin, plasma levels were detectable in approximately half of the subjects treated. However also in this case the soft gelatin capsules exhibited a higher individual absorption when compared with the corresponding data for the hard gelatin capsules. PMID- 11194174 TI - Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an experimental study. AB - The roots of Withania somnifera (WS) are used extensively in Ayurveda, the classical Indian system of medicine, and WS is categorized as a rasayana, which are used to promote physical and mental health, to provide defence against disease and adverse environmental factors and to arrest the aging process. WS has been used to stabilize mood in patients with behavioural disturbances. The present study investigated the anxiolytic and antidepressant actions of the bioactive glycowithanolides (WSG), isolated from WS roots, in rats. WSG (20 and 50 mg/kg) was administered orally once daily for 5 days and the results were compared by those elicited by the benzodiazepine lorazepam (0.5 mg/kg, i.p.) for anxiolytic studies, and by the tricyclic anti-depressant, imipramine (10 mg/kg, i.p.), for the antidepressant investigations. Both these standard drugs were administered once, 30 min prior to the tests. WSG induced an anxiolytic effect, comparable to that produced by lorazepam, in the elevated plus-maze, social interaction and feeding latency in an unfamiliar environment, tests. Further, both WSG and lorazepam, reduced rat brain levels of tribulin, an endocoid marker of clinical anxiety, when the levels were increased following administration of the anxiogenic agent, pentylenetetrazole. WSG also exhibited an antidepressant effect, comparable with that induced by imipramine, in the forced swim-induced 'behavioural despair' and 'learned helplessness' tests. The investigations support the use of WS as a mood stabilizer in clinical conditions of anxiety and depression in Ayurveda. PMID- 11194175 TI - Hypocrellin and hypericin-induced phototoxicity of HL-60 cells: apoptosis or necrosis? AB - Hypericin and hypocrellin are potential antiviral and antineoplastic agents with multiple modes of light-induced biological activity connected with a production of singlet oxygen and/or excited-state proton transfer and consequent pH drop formation in the drugs environment. In present work light-induced cytotoxicity of hypericin and hypocrellin and mechansim of cell death (apoptosis or necrosis) on human leukemic cell line HL-60 was studied. As a mean for apoptosis detection we used poly (ADP-ribose) polymerase (PARP) as a sensitive marker of early stages of apoptosis. Our results show that exposition of HL-60 cells to hypericin (1 x 10( 5) mol x l(-1)) for 4 hours has no effect on PARP cleavage. However, after 24 and 48 hours of illumination there is evident that hypericin in this concentration cleaved PARP (116 kDa) into two fragments (85 and 25 kDa). Contrary to hypericin, hypocrellin in concentration 1 x 10(-5) mol x l(-1) after 4 hours of illumination cleaved PARP into two fragments typical for apoptosis. In lower concentration (1 x 10(-6) mol x l(-1)) hypocrellin possess also significant cytotoxic activity. Because we detected no fragmentation of PARP in all observed time periods we suggest that cytotoxic effect of hypocrellin in this concentration is due to induction of necrosis. Our results support the hypotesis that the hypericin and hypocrellin has similar mechanism of action and illumination increases cytotoxic effect of both agents. PMID- 11194176 TI - Croton zehntneri essential oil: effects on behavioral models related to depression and anxiety. AB - Croton zehntneri (Cz), a popular plant used to treat "nervous disturbance", contains a complex mixture of compounds, including substances exhibiting central nervous system activity. The effects of Cz essential oil administration (p.o.) on the rat's central nervous system were studied in behavioral models used to evaluate anxiety and antidepressive drugs. The results showed that administration of Cz essential oil: 1) increased the immobility duration measured in the forced swimming test as compared to control group (control = 89.8 +/- 45.8; 1 microl = 153.0 +/- 48.7; 3 microl = 157.4 +/- 45.3; 10 microl = 145.3 +/- 51.0); 2) reduced the locomotion frequency observed in the open field (control = 62.5 +/- 22.7; 3 microl = 38.0 +/- 13.5; 10 microl = 39.2 +/- 22.2); 3) had no effect on the experimental group (1 microl) observed in open field; 4) had no effect on animals tested in social interactions, plus-maze and holeboard tests. These data suggest that Cz oil produced central depressor effects in rats without any anxiety alterations. These results may explain the popular use of this plant in Brazilian folk medicine for treating "nervous disturbances". PMID- 11194177 TI - Induction of cytotoxicity by chlorogenic acid in human oral tumor cell lines. AB - Millimolar concentrations of chlorogenic acid (CGA) showed higher cytotoxic activity against human oral squamous cell carcinoma (HSC-2) and salivary gland tumor (HSG) cell lines, as compared with that against human gingival fibroblast (HGF). The cytotoxic activity of CGA was significantly reduced by catalase or CoCl2, but not affected by FeCl3 or CuCl2. ESR spectroscopy showed that higher (millimolar) concentrations of CGA produced radicals under alkaline conditions, acting as a prooxidant, whereas lower concentrations of CGA scavenged superoxide and hydroxyl radical. CGA produced large DNA fragments (as identified by slightly faster migrating band of DNA on agarose gel electrophoresis) and nuclear condensation (as demonstrated by Hoechst (No. 33258) staining) in tumor cell lines. Activation of caspase was demonstrated by staining with M30 monoclonal antibody, which reacts with degradation products of cytokeratin 18. Contact with CGA for at least 6 h was necessary for irreversible cytotoxicity induction. Pretreatment of the cells with caspase 3 inhibitor partially inhibited the cytotoxic action of CGA. These date suggest that CGA induces cytotoxicity in oral tumor cell lines, possibly by hydrogen peroxide-mediated oxidation mechanism. PMID- 11194178 TI - Ampelopsis brevipedunculata (Vitaceae) extract inhibits a progression of carbon tetrachloride-induced hepatic injury in the mice. AB - Ampelopsis brevipedunculata (Maxim.) Trautv. (Vitaceae) has been used in Japanese herbal folk medicine to treat liver disease. The objective of this study is to evaluate the antihepatotoxic effect of A. brevipedunculata in the mice. An aqueous fraction was extracted by immersing the berries of the plant material in 40% ethanol for six months, followed by removing ethanol. Daily free access to the aqueous extract as drinking water greatly reduced the severity of hepatic injury, characterized by centrilobular necrosis, cytoplasmic vacuolation, cellular swelling, inflammation, and fibrosis in the mice receiving a nonlethal dose of carbon tetrachloride twice weekly during nine weeks. In addition, such a feeding regimen decreased the elevated levels of plasma glutamate oxaloacetate transaminase and glutamate pyruvate transaminase in the carbon tetrachloride administered mice. These results suggest that the feeding regimen with A. brevipedunculata extract inhibited a progression of hepatic injury induced by carbon tetrachloride. PMID- 11194179 TI - Curative property of Withania somnifera Dunal root in the context of carbendazim induced histopathological changes in the liver and kidney of rat. AB - The liver and kidney of rat underwent severe histopathological lesions when treated with a single bolus dose of carbendazim, a fungicide, particularly affecting the hepatocytes and the renal corpuscles, respectively. The effects appear to be manifestations of the microtubule-disrupting activity of carbendazim. Treatment of carbendazim-treated rats with the powder of tuberous root of Withania somnifera (Ashwagandha) for 48 days resulted in complete cure of these organs. The results indicate that Withania somnifera would be an effective curative for carbendazim-induced histopathological changes in the liver and kidney. PMID- 11194180 TI - Anti-ulcer compound from Voacanga africana with possible histamine H2 receptor blocking activity. AB - Voacanga africana is used in Cameroonian ethnomedicine for the treatment of peptic ulcers. We have tested the cytoprotective, anti-secretory and ulcer healing actions of an alkaloid (TN) obtained from the fruit extract. Oral administration of TN (50-100 mg/kg) dose-dependently prevented ulcer formation by HCl/ethanol (36-75%), absolute ethanol (43-75%), HCl-ethanol/indomethacin (58 84%), Pylorus ligation (31-100%), cold restraint stress (68-100%) and histamine (49-100%). The inhibitory effect at 50 and 100 mg/kg against HCl/ethanol was not suppressed by pre-treatment with indomethacin (20 mg/kg, i.p.). TN reduced Shay ligated gastric acid secretion from 77 mEq/l in the controls to 46 and 25 mEq/l for the 50 and 100 mg/kg doses. Augmented histamine-induced gastric acid secretion was reduced from 84 mEq/l in the controls to 45 and 21 mEq/l for the two doses of TN, with total inhibition of gastric and duodenal ulcers by the 50 mg/kg dose. Healing rate of chronic acetic acid-induced ulcers was 62 and 83%, respectively, for the dose of 50 and 100 mg/kg of TN compared with the controls. TN has gastric anti-secretory effects similar to histamine receptor blockers. Its cytoprotective and ulcer healing properties are related to its ability to strengthen gastric mucosal defenses through enhanced gastric mucus production. PMID- 11194181 TI - Effects of Tarchonanthus camphoratus and Eriocephalus africanus on nociception in mice and pyrexia in rats. AB - The affects of water extracts of the leaves of T. camphoratus and E. africanus on acetic acid- and hotplate-induced nociception and lipopolysaccharide-induced pyrexia were investigated. The writhing induced by acetic acid was significantly attenuated by T. camphoratus (50-100 mg/kg, i.p.), and E. africanus (50-200 mg/kg, i.p.). Similarly, the pain produced by the hot-plate was significantly antagonized by T. camphoratus (100 mg/kg, i.p.), and E. africanus (50-100 mg/kg, i.p.). T. camphoratus (100 mg/kg, i.p.), and E. africanus (100-200 mg/kg, i.p.) significantly attenuated the fever produced by the bacterial endotoxin (lipopolysaccharide, 50 microg/kg, i.m.). Paracetamol (500 mg/kg, i.p.), produced similar effect to T. camphoratus and E. africanus on acetic acid-induced writhes but did not affect the pain and the fever produced by the hot-plate and lipopolysaccharide respectively, to any significant extent. These results indicate that both T. camphoratus and E. africanus have analgesic and antipyretic properties. PMID- 11194182 TI - Interaction of Strychnos nux-vomica-products and iron: with reference to lipid peroxidation. AB - In this paper, it has been investigated that strychnine, the major active principle in the alcoholic extract of the seeds of Strychnos nux-vomica, is responsible for its antilipid peroxidative property. The mechanism of action of this drug is through the chelation of the free iron in the system. It has also been observed that strychnine does not have any pro-oxidant-property, because it does not convert Fe3+ to Fe2+ and vice versa in the reaction system, as has been observed with several other antioxidants. PMID- 11194183 TI - Investigation of topical application of procyanidin B-2 from apple to identify its potential use as a hair growing agent. AB - Procyanidin B-2 is a polyphenol compound we have identified in apple which acts as a hair-growing factor in the murine model both in vitro and in vivo. This report describes our investigation of the effects of 1% procyanidin B-2 tonic on human hair growth after sequential use for 6 months. A double-blind clinical test involving a total of 29 subjects was performed. Nineteen men in the procyanidin B 2 group and 10 men in the placebo control group were subjected to analyses. No adverse side effects were observed in either group. The hair-growing effect was evaluated using a macrophotography technique combined with measurements of the hair diameter of clipped hairs. The increase in number of total hairs in the designated scalp area (0.5 cm square = 0.25 cm2 area) of procyanidin B-2 group subjects after the 6-month trial was significantly greater than that of the placebo control group subjects (procyanidin B-2, 6.68 +/- 5.53 (mean +/- SD)/0.25 cm2; placebo, 0.08 +/- 4.56 (mean +/- SD)/0.25 cm2; P < 0.005, two-sample t test). The increase in number of terminal hairs, which are defined as hairs more than 60 microm in diameter, in the designated area (0.5 cm square = 0.25 cm2 area) of the procyanidin B-2 group subjects after the 6-month trial was significantly greater than that of the placebo control group subjects (procyanidin B-2, 1.99 +/- 2.58 (mean +/- SD)/0.25 cm2; placebo, -0.82 +/- 3.40 (mean +/- SD)/0.25 cm2; P < 0.02, two-sample t test). Procyanidin B-2 therapy shows potential as a safe and promising cure for male pattern baldness. PMID- 11194184 TI - The Korean version of the neuropsychiatric inventory: a scoring tool for neuropsychiatric disturbance in dementia patients. AB - The Neuropsychiatric Inventory (NPI) is a standardized, validated, and reliable tool to assess neuropsychiatric derangements in dementia patients. The aim of this study is to develop the Korean version of the NPI (K-NPI) and to test its reliability and usefulness in dementia patients. The subjects were 49 normal controls and 92 patients with Alzheimer's disease (43), vascular dementia (32), frontotemporal lobar degeneration (11), and other causes (6). Their caregivers familiar with the subjects' everyday behavior were interviewed with the K-NPI. In a subgroup (29/141) of the caregivers, the K-NPI was repeated for test-retest reliability, average of 23.1 days after the initial test. Prevalence rates of 12 behavioral domains in dementia patients were comparable to those of the original NPI; apathy was the most common and hallucination was the least common behavior. Total K-NPI scores correlated positively with dementia severity assessed with the Korean Mini-Mental State Examination. Test-retest reliabilities of frequencies and severities of all subscales were significantly high. Depression, anxiety, apathy, irritability, night-time behavior, and eating change were identified at very low rates in normal controls and were significantly less than those in dementia patients (p<0.001). The K-NPI, whose reliability and competency are comparable to those of the original version, may be a reliable and useful tool for measuring neuropsychiatric disturbances in Korean dementia patients. PMID- 11194185 TI - Serotypes and antimicrobial susceptibility in clinical isolates of Haemophilus influenzae from Korean children in prevaccination era. AB - Fifty-five strains of Haemophilus influenzae recovered at a children's hospital in Korea from 1992 through 1997, were analyzed for serotype and antibiotic resistance. Antimicrobial susceptibility was tested by broth dilution method. Among the 55 strains, 26 were from normally sterile body fluids, of which 17 were from the immunocompetent children. Spectrum in the immunocompetent included meningitis (47%), bacteremic pneumonia (18%), and bacteremia without focus (35%). Three (12%) of 26 invasive infections were caused by non-type b: one type d and two type f. Nine of 29 non-sterile body fluid isolates belonged to one of encapsulted serotypes: four a, two c, one of each of b, d and e. Thirty two (58%) strains were resistant to ampicillin, and all of which produced beta-lactamase. All of the strains were highly susceptible to amoxicillin/clavulanate, cefixime, cefuroxime, azithromycin and ciprofloxacin, while 1 (2%), 7 (13%), 4 (7%) and 4 (7%) strains were intermediate to cefprozil, cefaclor, loracarbef, and clarithromycin, respectively. The serotype distribution of H. influenzae in Korean children is similar to those in developed countries before the introduction of Hib conjugate vaccine, and ampicillin resistance rate is among the highest published to date. PMID- 11194186 TI - Serologic heterogeneity of HLA-A24 correlates with allelic types in the Korean population. AB - HLA-A24 is the second most frequently expressed HLA-A type in Koreans (GF 22.8%). Four different serologic reaction patterns were observed in Korean A24 positive samples using a commercial serologic typing kit. To clarify the nature of serologic heterogeneity, thirteen A24 positive DNA samples representing the four different serologic reaction patterns were subjected to DNA sequencing analysis of the amplified HLA-A genes from each sample. Four A*24 alleles (A*2402101, A*2403, A*2408, and A*2421) were associated with the four unique serologic reaction patterns. During this study, a novel allele, A*2421, was characterized. The new sequence is similar to A*2402101, differing at codon 127 (AAA-->AAC; K- >N). By comparing putative amino acid sequences and serologic reaction patterns of A*24 allelic products identified in this study, several crucial sites for A24- and A9-specific antibody binding were predicted: 127K for A24 antibody binding, and 62E-65G and 166D-167G for A9 antibody binding. This information will be helpful for accurately assigning HLA-A24 types by serology and for predicting serologic types of new alleles. PMID- 11194187 TI - Effectiveness of propofol pretreatment on the extent of deranged cerebral mitochondrial oxidative enzyme system after incomplete forebrain ischemia/reperfusion in rats. AB - It has been suggested that propofol has the protective effect on cerebral ischemia-reperfusion injury. The aim of this study is to evaluate the effect of propofol pretreatment on incomplete forebrain ischemia-reperfusion injury in rats. Thirty Sprague-Dawley rats were anesthetized with isoflurane in oxygen and randomly allocated into propofol group (n=13) and saline group (n=17). In propofol group, propofol was pretreated in a step-down scheme before inducing forebrain ischemia by occlusion of both common carotid arteries and arterial hypotension. After ischemia (20 min) and reperfusion (30 min), rats were decapitated. Brain was sliced to obtain coronal slices of 4-12 mm from frontal pole, which were reacted with 2% 2,3,5-triphenyl-2H-tetrazolium chloride (TTC) for 10 min to differentiate the damaged tissues from normal tissues. Median (interquartile range) values of the average percent infarct area were 0.0 (8.6)% and 20.1 (41.2)% in propofol and saline groups, respectively. There was significant difference between the groups. In conclusion, propofol may have a protective effect on incomplete forebrain ischemia-reperfusion injury. PMID- 11194188 TI - Presence of circulating autoantibodies against bronchial epithelia cell in patients with nonatopic asthma. AB - Allergic response to common environmental agents has been regarded as a main pathogenetic mechanism of bronchial asthma. However, allergic sensitization (atopy) can not be detected in a siginificant number of adult asthmatic patients. The etiology of nonatopic asthma has not yet been defined. To evaluate the possible involvement of autoimmune response against bronchial mucosa in the pathogenesis of nonatopic asthma, we performed indirect immunofluorescence staining of fresh frozen human bronchial mucosa tissue using serum samples from patients with atopic and nonatopic asthma, healthy controls, and patients with systemic lupus erythematosus. On immunostaining, circulating IgG autoantibodies against bronchial mucosa were detected in 2 (9.1%) of 22 patients with nonatopic asthma and in none of 22 patients with atopic asthma and of 22 healthy controls. IgG autoantibodies from the two patients with nonatopic asthma predominantly stained the cytoplasmic membrane of basal cells in bronchial epithelium. Serum samples from 10 patients with systemic lupus erythematosus immunostained the nucleus of epithelial cells in whole layer of bronchial epithelium. This study showed the presence of circulating IgG autoantibodies against the bronchial epithelial cell in a small portion of patients with nonatopic asthma. Further studies may be necessary to evaluate the possible involvement of autoimmune mechanism in the pathogenesis of nonatopic asthma. PMID- 11194189 TI - Change in activity of the sympathetic nervous system in diet-induced obese rats. AB - We investigated the change in activity of the sympathetic nervous system (SNS) in high-sucrose diet (HSD)-induced obese rats compared with controls. Power spectral analyses of R-R interval variability were performed to obtain the low frequency (LF, 0.04-0.699 Hz) and high frequency (HF, 0.7-3.0 Hz) powers. The percents of fat mass to body weight (%F/BW) and fat to muscle ratios (F/M) were significantly increased in HSD-fed rats. Plasma glucose, leptin, and triglyceride concentrations in rats fed with HSD were significantly increased. LF in normalized units (LFn), which represents both sympathetic and parasympathetic activities, was significantly increased whereas HF in normalized unit (HFn), which represents parasympathetic activity, was significantly decreased in HSD-fed rats. LF/HF, which represents sympathetic activity, was significantly increased in HSD-fed rats and was correlated with leptin (r=0.549, p<0.023), %F/BW (r=0.513, p<0.035), F/M (r=0.536, p<0.038), and triglyceride (r=0.497, p<0.042). When adjusted for leptin concentrations, however, LF/HF of HSD-fed rats was significantly decreased. In conclusion, HSD-induced obese rats showed increased LF/HF, which was significantly decreased by adjustment for leptin concentrations. We suggest that stimulating effect of leptin on SNS is reduced, which might play a role in induction of obesity by HSD. PMID- 11194190 TI - Relationship between normal heart size and body indices in Korean. AB - We provided a curve-fit equation to predict the normal heart weight (g) in Koreans by examining 422 autopsies (215 males and 207 females, from newborn to age 77 yr) who were relatively in good general condition. Heart weight was well correlated with body surface area (m2), body weight (kg), and body height (cm) but poorly with age in both sex. Heart weight progressively increased from birth to the earlier 3rd and 4th decades in male and female, respectively, and then gradually decreased; mean heart weight of all age group was greater in male than in female and significantly different from birth to 4th decade. In both sex, heart weight exponentially increased in accordance with the increase of body height, body weight, and body surface (in male, heart weight=0.00312 x body height(2.239), r2=0.750, p<0.0001; in female, heart weight=0.00443 x body height(2170), r2=0.781, p<0.0001; in male, heart weight=9.22 x body weight(0.853), r2=0.770, p<0.0001; in female, heart weight=9.00 x body weight0.855, r2=0.820, p<0.0001; in male, heart weight=155.18 x body surface area1.290, r=0.808, p<0.0001; in female, heart weight=124.13 x body surface area1.242, r=0.834, p<0.0001). These results indicate that heart weight is better correlated with body surface area than with body weight; however, body weight should be a better determinant of a predicted heart weight, since body surface area is entirely dependent on body height and body weight. PMID- 11194191 TI - Expression of progesterone receptor in human keratinocytes. AB - Despite the various responses of human skin to female sex hormones, cellular and subcellular targets and the mechanisms of action of estrogen and progesterone in human skin are not well understood. The detection of estrogen receptor (ER) and progesterone receptor (PR) in the skin is of great importance to understand the effect of estrogen and progesterone. In primary cultures of human keratinocytes, expression of ER and PR was monitored by immunocytochemistry and reverse transcriptase polymerase chain reaction (RT-PCR). Paraffin embedded skin tissues were stained with monoclonal antibodies to human ER and PR by immunohistochemistry. Cultured human keratinocytes expressed cytoplasmic PR protein and PR mRNA transcripts. By contrast, ER was detected only at the mRNA level. Suprabasal keratinocytes from samples of pruritic urticarial papules, plaques of pregnancy (PUPPP) and psoriasis were stained positively only for PR, while those from samples of erythema nodosum were negative for both ER and PR. Lesional epidermis of PUPPP showed positive PR immunoreactivity, while nonlesional epidermis did not. No other cells in the normal human skin were stained with ER and PR. The present study suggests that by expressing PR human keratinocytes act as targets for progesterone action. PMID- 11194192 TI - Prognostic significance of E-cadherin/catenin complex expression in gastric cancer. AB - Abnormal expression of E-cadherin/catenin complex in cancer has been associated with poor differentiation and acquisition of invasiveness, suggesting a possible role of this protein as an invasion suppressor. In this study, we conducted an immunohistochemical investigation of all components of the E-cadherin/catenin complex in 65 gastric cancer patients. Abnormal expression of E-cadherin and, alpha- and gamma-catenin occurred more frequently in diffuse than in intestinal type of gastric cancer, and correlated with poor differentiation. Abnormal expression of E-cadherin and beta-catenin correlated with poor survival. Abnormal expression of all four components of the complex was associated with poorly differentiated and diffuse-type carcinoma, and poor survival. In the multivariate analysis, abnormal expression of the E-cadherin/catenin complex was not an independent prognostic factor. These results suggest that the E-cadherin/catenin complex may be a useful marker of differentiation and prognosis in gastric cancer. Further studies are warranted to clarify the impact of the E cadherin/catenin complex on prognostic factor of gastric cancer. PMID- 11194193 TI - Topographic expression of p21WAF1/SDI1/CIP1, bcl2, and p53 is altered at the early stage of colorectal carcinogenesis. AB - We analyzed the expression of p21, bcl2, and p53 in normal and different pathologic mucosa of the human colorectum using immunohistochemistry and cold polymerase chain reaction-single strand conformation polymorphism. The topography of normal mucosa showed; bcl2 and p53 expression restricted to basal epithelial cells and p21 expressed only in superficial epithelial cells. This topographic expression was altered in hyperplastic polyps and adenomas. Hyperplastic polyps revealed absence of or weak bcl2 expression and strong p21 expression without topography. In adenomas, whereas bcl2 expression increased and extended to parabasal and superficial dysplastic epithelium, the increase of p21 expression was limited to surface dysplastic epithelium. p53 was weakly expressed throughout the full thickness of dysplastic epithelium. Bcl2 expression in adenomas was stronger than in carcinomas; p53 expression was converse and p21 expression was variable. In carcinomas, this topographic expression was largely abrogated but p53 mutation (36%) was more frequent than in adenomas (2%). In carcinomas, p21 and p53 expression correlated inversely, but there was no relationship with bcl2. These results suggest that there is precisely ordered topographic pattern of p21, bcl2, and wild p53 expression in normal colorectal cells, but this becomes disordered during the early stage of colorectal carcinogenesis. PMID- 11194194 TI - Incidence pattern of colorectal cancer in Korea by subsite of origin. AB - It has been suggested that colorectal cancer might not be one homogenous disease entity, based on the distinctive characteristics of its subsite of origin. Incidence data on 4,987 colorectal cancer were obtained from the Seoul Cancer Registry between 1993 and 1995. Age, sex, and subsite-specific incidence rates were compared. The age-standardized annual incidence rates of total colorectal cancer were 26.1 and 18.0 per 100,000 for men and women, respectively. There were no appreciable difference in the rates of colon and rectal cancer for either sex (colon vs rectum: 12.8 vs. 13.2 for men, 9.3 vs. 8.6 for women). The incidence rate of right colon was slightly higher in men than in women, and this discrepancy became even greater in left colon (men vs women: 3.5 vs. 3.0 for right colon, 4.7 vs. 2.9 for left colon). When the incidence rate of right colon was compared with that of left colon, women had a higher rate in the right colon among the elderly, aged 60 yr and over and a lower rate at age 40 yr or less, while the opposite was observed for men. More analytic approaches are needed to identify which factors are related with these descriptive results in colorectal cancer incidence. PMID- 11194195 TI - A rat model for radiation-induced proctitis. AB - Radiation proctitis is a frequent acute complication encountered with pelvic irradiation. This study was aimed at establishing the optimal radiation dose for radiation-induced proctitis in rats. Female Wistar rats were used. The rectal specimens were examined morphologically at 5th and 10th day following 10-30 Gy irradiation in single fraction. With increasing dose, mucosal damage became worse, and there was a prominent reaction after > or =15 Gy. We selected 17.5 Gy as an optimal dose for radiation proctitis and examined specimens at day 1-14 and at week 4, 6, 8, and 12 after 17.5 Gy. The rectal mucosa revealed characteristic histological changes with time. An edema in lamina propria started as early as 1 2 days after irradiation and progressed into acute inflammation. On day 7 and 8, regeneration was observed with or without ulcer. Four weeks later, all regeneration processes have been completed with end result of either fibrosis or normal appearing mucosa. This study showed that the radiation injury of the rectum in rat develops in dose-dependent manner as it has reported in previous studies and suggested that 17.5 Gy in single fraction is the optimum dose to evaluate the protective effect of various medications for radiation proctitis in face of the clinical situation. PMID- 11194196 TI - Association of serum lipids and glucose with the risk of colorectal adenomatous polyp in men: a case-control study in Korea. AB - Previous studies on life style for colorectal cancer risk suggest that serum lipids and glucose might be related to adenomatous polyps as well as to colorectal carcinogenesis. This case-control study was conducted to investigate the associations between serum lipids, blood glucose, and other factors and the risk of colorectal adenomatous polyp. Male cases with colorectal adenomatous polyp, histologically confirmed by colonoscopy (n=134), and the same number of male controls matched by age for men were selected in hospitals in Seoul, Korea between January 1997 and October 1998. Serum lipids and glucose levels were tested after the subjects had fasted for at least 12 hr. Conditional logistic regression showed that there was a significant trend of increasing adenomatous polyp risk with the rise in serum cholesterol level (Ptrend=0.07). Increasing trend for the risk with triglyceride was also seen (Ptrend=0.01). HDL-cholesterol and LDL-cholesterol had increasing trends for the risk, which were not significant. In particular, it was noted that higher fasting blood glucose level reduced the adenomatous polyp risk for men (Ptrend=0.001). This study concluded that both serum cholesterol and triglyceride were positively related to the increased risk for colorectal adenomatous polyp in Korea. Findings on an inverse relationship between serum glucose and the risk should be pursued in further studies. PMID- 11194197 TI - The significance of CD44 variants expression in colorectal cancer and its regional lymph nodes. AB - CD44 is a cell adhesion molecule with numerous isoforms created by mRNA alternative splicing. Expression of CD44 variants has been suggested to play a potential role in tumor progression and metastasis. We designed primers CD44V, CD44V6/7, CD44R1 and CD44V6-10 to analyze and compare the roles of each CD44 variants. Expressions of CD44 variants were investigated in normal colonic mucosa, the lymph nodes which was histopathologically free of cancer cell, and cancer tissues of 44 human colorectal cancer patients by RT-PCR method. The expression of CD44V was observed in 28 out of 39 (71.8%) tumors and 7 out of 11 (63.6%) N1 normal regional lymph nodes, and CD44V6/7 was observed in 28 out of 39 (71.8%) tumors and 9 out of 11 (81.8%) N1 normal regional lymph nodes. The expressions of CD44V and CD44V6/7 were most frequently observed compared with any other CD44 variants. In normal colonic mucosa, the expression of CD44 variants are low but in cancer tissue and its regional lymph node, the expression of CD44V and CD44V6/7 were significantly higher and more frequent than any other CD44 variants (p<0.05). These results suggest that CD44V and CD44V6/7 can be a molecular marker for colorectal cancer and its micrometastasis to the regional normal lymph node. PMID- 11194198 TI - Successful treatment in the patient with serum sodium level greater than 200 mEq/L. AB - Hypernatremia developing in nonhospitalized adults is predominantly a disease of the elderly and mentally handicapped patients, possibly revealing inadequate nursing care of these patients. It has long been claimed that the duration of hypernatremia and its rate of correction are correlated with improvement in patients' neurologic status. Since there are only a handful of cases with serum sodium levels greater than 200 mEq/L until recently, it is not clear at what rate plasma sodium concentration can be safely normalized in severe hypernatremic patients. We report a case of severe hypernatremia with survival. This patient underwent rapid correction of serum sodium concentration during the management of this metabolic derangement using isotonic solution. PMID- 11194199 TI - Fungal discitis due to Aspergillus terreus in a patient with acute lymphoblastic leukemia. AB - We report a case of Aspergillus terreus discitis which developed in a patient with acute lymphoblastic leukemia following induction chemotherapy. A. terreus was isolated from sputum, one month earlier, but the physician did not consider it significant at the time. Magnetic resonance imaging study showed the involvement of L3-4, L4-5 and L5-S1 intervertebral discs. Etiology was established by means of histology and culturing a surgical specimen of disc materials. Our patient survived after a surgical debridement and amphotericin B administration with a total dose of 2.0 g. Discitis caused by Aspergillus terreus is a very rare event. A. terreus is one of the invasive Aspergillus species. The pathogenetic mechanism is discussed and the literature is reviewed. PMID- 11194200 TI - Toxic amebic colitis coexisting with intestinal tuberculosis. AB - A patient with a fulminant amebic colitis coexisting with intestinal tuberculosis had a sudden onset of crampy abdominal pain, mucoid diarrhea, anorexia, fever and vomiting with signs of positive peritoneal irritation. Fulminant amebic colitis occurring together with intestinal tuberculosis is an uncommon event and may present an interesting patho-etiological relationship. The diagnosis was proven by histopathologic examination of resected specimen. Subtotal colectomy including segmental resection of ileum, about 80 cm in length, followed by exteriorization of both ends, was performed in an emergency basis. Despite all measures, the patient died on the sixth postoperative day. The exact relationship of fulminant amebic colitis and intestinal tuberculosis is speculative but the possibility of a cause and effect relationship exists. Fulminant amebic colitis may readily be confused with other types of inflammatory bowel disease, such as idiopathic ulcerative colitis, Crohn's disease, perforated diverticulitis and appendicitis with perforation. This report draws attention to the resurgence of tuberculosis and amebiasis in Korea, and the need for the high degree of caution required to detect it. PMID- 11194201 TI - Extensive acute lung injury following limited thoracic irradiation: radiologic findings in three patients. AB - The aim of our study was to describe the radiologic findings of extensive acute lung injury associated with limited thoracic irradiation. Limited thoracic irradiation occasionally results in acute lung injury. In this condition, chest radiograph shows diffuse ground-glass appearance in both lungs and thin-section CT scans show diffuse bilateral ground-glass attenuation with traction bronchiectasis, interlobular septal thickening and intralobular smooth linear opacities. PMID- 11194202 TI - Intraoperative radiation therapy as an adjunctive therapy for huge and highly vascular parasagittal meningiomas. AB - This case presents a 34-year-old man who had a huge parasagittal meningioma. Initial treatment consisted of preoperative external carotid artery embolization and partial tumor resection. During the resection, we found that the tumor invaded the adjacent calvarium, and due to massive hemorrhage, total removal of the tumor was impossible. The patient was treated with intraoperative radiation therapy (IORT) (25 Gy via 16 MeV) as an adjunctive therapy. Eight months after IORT, we were able to remove the tumor completely without surgical difficulties. IORT can be considered an useful adjunctive therapy for the superficially located, huge, and highly vascular meningioma. PMID- 11194203 TI - Macular amyloidosis presented as poikiloderma: a case report. AB - We report a 51-year-old Vietnam War veteran with an unusual variant of macular amyloidosis presenting as poikilodermatous skin lesions. The extensive mottled brown pigmentation was checkered with small hypopigmented or normal skin-colored spots and intermingled with telangiectasia. Skin biopsy revealed subepidermal amyloid deposits. There was no evidence of extracutaneous involvements. This case could be easily confused with other true poikiloderma lesions. PMID- 11194204 TI - A sensible formulation of the significance test. AB - The conventional procedure for null hypothesis significance testing has long been the target of appropriate criticism. A more reasonable alternative is proposed, one that not only avoids the unrealistic postulation of a null hypothesis but also, for a given parametric difference and a given error probability, is more likely to report the detection of that difference. PMID- 11194205 TI - Using just noticeable differences to interpret test scores. AB - This study explored the value of obtaining a just noticeable difference (JND) for a test--the difference in scores needed before observers detect a difference in examinees' behavior--as a means of interpreting the practical meaning of scores. Classical psychophysical methods were adapted and applied to the scores of foreign teaching assistants (TAs) on an achievement test, the Test of Spoken English (TSE), and the ratings for English proficiency that the TAs received from their students. The JND for the TSE scores was substantial, as large as the standard deviation of the scores and much larger than the standard error of measurement and guidelines for the d index of effect size for mean differences, suggesting that both sets of standards may highlight score differences that are not practically significant. This study demonstrates the applicability of JNDs for evaluating scores on educational and psychologists' tests. PMID- 11194206 TI - The consequence of ignoring a nested factor on measures of effect size in analysis of variance. AB - Although the consequences of ignoring a nested factor on decisions to reject the null hypothesis of no treatment effects have been discussed in the literature, typically researchers in applied psychology and education ignore treatment providers (often a nested factor) when comparing the efficacy of treatments. The incorrect analysis, however, not only invalidates tests of hypotheses, but it also overestimates the treatment effect. Formulas were derived and a Monte Carlo study was conducted to estimate the degree to which the F statistic and treatment effect size measures are inflated by ignoring the effects due to providers of treatments. These untoward effects are illustrated with examples from psychotherapeutic treatments. PMID- 11194207 TI - Sample size and multiple regression analysis. AB - Despite the development of procedures for calculating sample size as a function of relevant effect size parameters, rules of thumb tend to persist in designs of multiple regression studies. One explanation for their persistence may be the difficulty in formulating a reasonable a priori value of an effect size to be detected. This article presents methods for calculating effect sizes in multiple regression from a variety of perspectives and also introduces a new method based on an exchangeability structure among predictor variables. No single method is deemed superior, but rather examples show that a combination of methods is likely to be most valuable in many situations. A simulation provides a 2nd explanation for why rules of thumb for choosing sample size have persisted but also shows that the outcome of such underpowered studies will be a literature consisting of seemingly contradictory results. PMID- 11194208 TI - A comparison of subset selection and analysis of covariance for the adjustment of confounders. AB - Two common methods for adjusting group comparisons for differences in the distribution of confounders, namely analysis of covariance (ANCOVA) and subset selection, are compared using real examples from neuropsychology, theory, and simulations. ANCOVA has potential pitfalls, but the blanket rejection of the method in some areas of empirical psychology is not justified. Assumptions of the methods are reviewed, with issues of selection bias, nonlinearity, and interaction emphasized. Advantages of ANCOVA include better power, improved ability to detect and estimate interactions, and the availability of extensions to deal with measurement error in the covariates. Forms of ANCOVA are advocated that relax the standard assumption of linearity between the outcome and covariates. Specifically, a version of ANCOVA that models the relationship between the covariate and the outcome through cubic spline with fixed knots outperforms other methods in simulations. PMID- 11194209 TI - Measurement and structural models for children's problem behaviors. AB - This article considers an analytic strategy for measuring and modeling child and adolescent problem behaviors. The strategy embeds an item response model within a hierarchical model to define an interval scale for the outcomes, to assess dimensionality, and to study how individual and contextual factors relate to multiple dimensions of problem behaviors. To illustrate, the authors analyze data from the primary caregiver ratings of 2,177 children aged 9-15 in 79 urban neighborhoods on externalizing behavior problems using the Child Behavior Checklist 4-18 (T. M. Achenbach, 1991a). Two subscales, Aggression and Delinquency, are highly correlated, and yet unidimensionality must be rejected because these subscales have different associations with key theoretically related covariates. PMID- 11194210 TI - Combining independent p values: extensions of the Stouffer and binomial methods. AB - The Stouffer z method, and other popular methods for combining p values from independent significance tests, suffer from three problems: vulnerability to criticisms of the individual studies being pooled, difficulty in handling the "file drawer problem," and vague conclusions. These problems can be reduced or eliminated by supplementing a test of combined probability with a variety of new analyses described here. Along with other advantages, these analyses provide a way to address the file drawer problem without making limiting assumptions about the nature of studies not included in the pooled analysis. These analyses can supplement a traditional meta-analysis, yielding conclusions not provided by widely used meta-analytic procedures. PMID- 11194211 TI - Promoting behavioral science research in diabetes. PMID- 11194212 TI - Relationship between electroneurographic changes and serum ubiquitin levels in patients with type 2 diabetes. AB - OBJECTIVE: The aim of the present study was to investigate any relationship between serum ubiquitin levels and electroneurographic changes in peripheral nerves for patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: The study involved 34 patients (19 men, 15 women; mean age 46 +/- 13 years) with type 2 diabetes. Serum ubiquitin values were measured by sandwich enzyme-linked immunosorbent assay Measurement of nerve conduction velocity (NCV) was performed on three motor (median, tibial, and peroneal) and three sensory (median, ulnar, and sural) nerves. The value of motor compound muscle action potential (CMAP) was obtained from the sum of median, tibial, and peroneal motor nerve amplitudes, and sensory compound nerve action potential (CNAP) was computed as the sum of median and ulnar sensory nerve amplitudes. RESULTS: Patients with diabetes were divided into three groups: group 1 (n = 8) had normal electroneurography results, group 2 (n = 8) had slowed NCV, and group 3 (n = 18) had low values of motor CMAP and/or sensory CNAP as well as slowed NCV. Mean ubiquitin level in group 3 (20.4 +/- 2.9 ng/dl) was significantly higher than that in group 1 (11.2 +/- 1.1 ng/dl, t = 11.5, P < 0.0001) and group 2 (13.2 +/- 2.7 ng/dl, t = 5.9, P < 0.0001). Serum ubiquitin levels were inversely correlated with motor CMAP (r = -0.68) and sensory CNAP (r = -0.61) values. CONCLUSIONS: The results of this study indicate that there could be a relationship between the diminished amplitudes of axons of the peripheral nerve and the increase in serum ubiquitin levels in patients with type 2 diabetes. Further studies are required to confirm this relationship. PMID- 11194213 TI - Involvement of peripheral polymorphonuclear leukocytes in oxidative stress and inflammation in type 2 diabetic patients. AB - OBJECTIVE: To determine the extent to which peripheral polymorphonuclear leukocytes (PMNs) contributed to oxidative stress (OS) and inflammation in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: PMNs and plasma were separated from blood withdrawn from 18 type 2 diabetic patients and 16 age- and sex-matched normal control subjects. The rate of superoxide release from phorbol 12-myristate 13-acetate (PMA)-stimulated PMNs and the plasma glutathione (GSH) levels served as measures of OS. Inflammation was assessed by PMN recruitment, expressed by peripheral blood PMN counts, and the in vitro survival of PMNs, which reflects cell necrosis. RESULTS: PMA-stimulated PMNs from diabetes released superoxide significantly faster, and plasma-reduced GSH was lower in diabetic patients than in normal control subjects. The rate of superoxide release from diabetic PMNs showed no correlation with the plasma glucose concentrations, whereas a positive linear correlation with HbA1c was found. The in vitro survival of diabetic PMNs was lower than normal control PMNs when each was incubated in its own serum. The in vitro survival of normal control PMNs was reduced when incubated with diabetic serum, whereas normal control sera promoted the survival of diabetic PMNs. Peripheral PMN counts were higher in diabetic patients than in normal control patients. CONCLUSIONS: Type 2 diabetes is accompanied by a priming of PMNs, resulting in OS and increased self-necrosis. Necrosis starts a chain of inflammatory reactions that result in cell recruitment and in the long run, with OS, may result in endothelial dysfunction. Understanding the contribution of PMNs to OS and inflammation in diabetes may illuminate new mechanisms through which endothelial dysfunction evolves and causes angiopathy and atherosclerosis. PMID- 11194214 TI - Flexible meal-related dosing with repaglinide facilitates glycemic control in therapy-naive type 2 diabetes. AB - OBJECTIVE: This double-blind randomized placebo-controlled parallel group study assessed the efficacy and safety (with particular regard to body weight and hypoglycemia) of repaglinide when used in a flexible mealtime dosing regimen in a situation close to everyday clinical practice. RESEARCH DESIGN AND METHODS: A total of 408 patients with type 2 diabetes considered poorly controlled by diet, but without a history of previous antidiabetic medication, were randomized to receive 0.5 mg repaglinide at mealtimes (increased to 1 mg after 4 weeks depending on blood glucose response) or placebo for 16 weeks. Patients were free to choose a flexible meal pattern, adjusting the dosing schedule from two to four preprandial doses per day in accordance with a "one meal, one dose; no meal, no dose" principle. Additional snacks were not a requirement of the treatment schedule. RESULTS: Treatment with repaglinide significantly improved glycemic control with respect to baseline and placebo, reducing HbA1c by 1.14% from baseline and fasting plasma glucose by 1.8 mmol/l. Improvement in glycemic control was independent of the meal pattern adopted by patients, including those most commonly taking two or four meals daily, with no correlation between meal pattern and risk of hypoglycemia. The improvement in glycemic control was also independent of degree of obesity and age < or =65 or >65 years. There was no significant body weight increase in the repaglinide group. CONCLUSIONS: Mealtime dosing with repaglinide is effective in improving overall glycemic control in type 2 diabetic patients for which control is suboptimal using diet alone. Patients are able to vary their meal pattern from a conventional regimen of three meals daily without compromising control or increasing the risk of adverse events. PMID- 11194215 TI - Sodium sensitivity related to albuminuria appearing before hypertension in type 2 diabetic patients. AB - OBJECTIVE: To find whether sodium sensitivity of blood pressure appears before hypertension and whether the sensitivity is related to diabetic nephropathy, we examined type 2 diabetic patients with normal levels of serum creatinine. RESEARCH DESIGN AND METHODS: A total of 32 patients were divided into three age matched groups: 11 patients had normoalbuminuria, 12 had microalbuminuria, and 9 had macroalbuminuria. Patients stayed on a diet with ordinary sodium levels for 1 week and a sodium-restricted diet for 1 week, in random order. Urinary excretion of sodium and albumin and systemic blood pressure were measured daily. A pressure natriuresis curve was drawn by linkage of the two datum points obtained in the steady state during the different diets. We calculated the sodium sensitivity index as the reciprocal of the slope of this curve. RESULTS: The median sodium sensitivity index and the mean blood pressure were higher in micro- and macroalbuminuric patients than in normoalbuminuric patients. Eighteen patients were without hypertension (<140/90 mmHg); of these, 10 had blood pressure readings <130/85 mmHg with ordinary sodium levels. Urinary albumin was correlated with the index but not with blood pressure. For these 10 patients, the index in those with albuminuria was higher than in those with normoalbuminuria. In such patients with albuminuria, sodium restriction decreased albuminuria and blood pressure. CONCLUSIONS: In type 2 diabetic patients with albuminuria but normal levels of serum creatinine, sodium sensitivity of blood pressure appears before hypertension and is related to albuminuria; sodium restriction is one treatment for diabetic nephropath, even without hypertension. PMID- 11194216 TI - Behavioral science research in diabetes: lifestyle changes related to obesity, eating behavior, and physical activity. AB - Lifestyle factors related to obesity, eating behavior, and physical activity play a major role in the prevention and treatment of type 2 diabetes. In recent years, there has been progress in the development of behavioral strategies to modify these lifestyle behaviors. Further research, however, is clearly needed, because the rates of obesity in our country are escalating, and changing behavior for the long term has proven to be very difficult. This review article, which grew out of a National Institute of Diabetes and Digestive and Kidney Diseases conference on behavioral science research in diabetes, identifies four key topics related to obesity and physical activity that should be given high priority in future research efforts: 1) environmental factors related to obesity, eating, and physical activity; 2) adoption and maintenance of healthful eating, physical activity, and weight; 3) etiology of eating and physical activity; and 4) multiple behavior changes. This review article discusses the significance of each of these four topics, briefly reviews prior research in each area, identifies barriers to progress, and makes specific research recommendations. PMID- 11194217 TI - Report of the health care delivery work group: behavioral research related to the establishment of a chronic disease model for diabetes care. AB - As one of four work groups for the November 1999 conference on Behavioral Science Research in Diabetes, sponsored by the National Institute on Diabetes and Digestive and Kidney Diseases, the health care delivery work group evaluated the status of research on quality of care, patient-provider interactions, and health care systems' innovations related to improved diabetes outcomes. In addition, we made recommendations for future research. In this article, which was developed and modified at the November conference by experts in health care delivery, diabetes and behavioral science, we summarize the literature on patient-provider interactions, diabetes care and self-management support among underserved and minority populations, and implementation of chronic care management systems for diabetes. We conclude that, although the quality of care provided to the vast majority of diabetic patients is problematic, this is principally not the fault of either individual patients or health care professionals. Rather, it is a systems issue emanating from the acute illness model of care, which still predominates. Examples of proactive population-based chronic care management programs incorporating behavioral principles are discussed. The article concludes by identifying barriers to the establishment of a chronic care model (e.g., lack of supportive policies, understanding of population-based management, and information systems) and priorities for future research in this area needed to overcome these barriers. PMID- 11194218 TI - Management of hyperglycemic crises in patients with diabetes. PMID- 11194219 TI - The Starr County Diabetes Education Study: development of the Spanish-language diabetes knowledge questionnaire. AB - OBJECTIVE: This study reports the psychometric properties of the 24-item version of the Diabetes Knowledge Questionnaire (DKQ). RESEARCH DESIGN AND METHODS: The original 60-item DKQ was administered to 502 adult Mexican-Americans with type 2 diabetes who are part of the Starr County Diabetes Education Study. The sample was composed of 252 participants and 250 support partners. The subjects were randomly assigned to the educational and social support intervention (n = 250) or to the wait-listed control group (n = 252). A shortened 24-item version of the DKQ was derived from the original instrument after data collection was completed. Reliability was assessed by means of Cronbach's coefficient alpha. To determine validity, differentiation between the experimental and control groups was conducted at baseline and after the educational portion of the intervention. RESULTS: The 24-item version of the DKQ (DKQ-24) attained a reliability coefficient of 0.78, indicating internal consistency, and showed sensitivity to the intervention, suggesting construct validation. CONCLUSIONS: The DKQ-24 is a reliable and valid measure of diabetes-related knowledge that is relatively easy to administer to either English or Spanish speakers. PMID- 11194220 TI - American Diabetes Association 60th Scientific Sessions, 2000: thiazolidinediones, obesity, and related topics. PMID- 11194221 TI - Oxidative stress in families of type 1 diabetic patients: further evidence. PMID- 11194222 TI - Failure to develop hepatic injury from rosiglitazone in a patient with a history of troglitazone-induced hepatitis. PMID- 11194223 TI - Plasma lipoprotein subpopulation distribution in Caucasian and African-American women with gestational diabetes. PMID- 11194224 TI - Thyrotoxicosis masked by diabetic ketoacidosis: a fatal complication. PMID- 11194225 TI - Beta-cell autoimmunity, genetic susceptibility, and progression to type 1 diabetes in unaffected schoolchildren. PMID- 11194226 TI - Type 1 diabetes and arterial dysfunction in asymptomatic Chinese adults. PMID- 11194227 TI - Lipoatrophy associated with lispro insulin in insulin pump therapy: an old complication, a new cause? PMID- 11194228 TI - Clinical evaluation of a newly designed compliant side port catheter for an insulin implantable pump: the EVADIAC experience. Evaluation dans le Diabete du Traitement par Implants Actifs. PMID- 11194229 TI - Efficacy of Tibetan medicine as an adjunct in the treatment of type 2 diabetes. PMID- 11194230 TI - Therapeutic benefits of ACE inhibitors and other antihypertensive drugs in patients with type 2 diabetes. PMID- 11194231 TI - Environmental factors and type 1 diabetes. PMID- 11194232 TI - Efficacy of octreotide in the therapy of severe nonproliferative and early proliferative diabetic retinopathy: a randomized controlled study. Response to Grant et al. PMID- 11194233 TI - 4-g monofilament is clinically useful for detecting diabetic peripheral neuropathy. PMID- 11194234 TI - Applying the diabetes quality improvement project indicators in the Indian Health Service primary care setting. AB - OBJECTIVE: With publication of the Diabetes Quality Improvement Project (DQIP) measures, the Indian Health Service National Diabetes Program applied the DQIP format to its IHS Diabetes Care and Outcomes Audit for comparison and benchmarks. RESEARCH DESIGN AND METHODS: Since 1986 the IHS Diabetes Care and Outcomes Audit has been conducted by medical record review in >75% of IHS and tribal facilities. Each year systematic random sample of charts is drawn from local diabetes registries. Chart reviews are conducted by, trained professionals according to standard definitions and instructions. Abstracted data are entered into a microcomputer-based epidemiologic software package. Local, regional, and national rates are constructed for each item. During the period 1995-1997, 150 facilities submitted data for compilation, representing participation from all 12 IHS administrative regions. The IHS Diabetes Care and Outcomes Audit collected virtually all of the DQIP measures, with the exception of LDL cholesterol (which was added to the record review in 1998). RESULTS: In 1995, 1996, and 1997, a total of 9,557, 9,985, and 9,626 individuals, respectively, were included in the total IHS audit sample. The reviews for 1995, 1996, and 1997 revealed that of all subjects: 55, 65, and 80%, respectively, had more than one HbA1c test during the year (P < 0.001); 42, 38, and 34%, respectively; had a high-risk HbA1c (>9.5%) (P < 0.001); 83, 81, and 84%, respectively, were tested for macroproteinuria (P < 0.11) and 16, 17, and 23%, respectively were tested for microproteinuria (P < 0.001); total cholesterol was assessed in 80, 81, and 85%, respectively (P < 0.001), and corresponding proportions of those with values <5.17 mmol/l were 48, 50, and 52%, respectively; triglyceride values were measured for 75,75, and 80%, respectively (P < 0.001), and the corresponding median triglyceride levels were 199, 198, and 193 mg/dl, respectively (P < 0.001); the proportion of clients with a blood pressure <140/90 mmHg was 64, 64, and 66%, respectively (P < 0.05); 55, 56, and 55%, respectively, had a dilated eye exam (P < 0.053); and the proportion of clients who had a comprehensive foot exam were 59, 59, and 61%, respectively (P < 0.05). CONCLUSIONS: The DQIP accountability and quality improvement measures could be easily applied to the IHS Diabetes Care and Outcomes Audit, and the process can prove to be practical. However, data alone are not sufficient to effect change. Use of the measures to ensure that the quality of care improves must also be stressed, because measuring alone will not guarantee such improvement. PMID- 11194235 TI - Comparative analysis of organ-specific autoantibodies and celiac disease- associated antibodies in type 1 diabetic patients, their first-degree relatives, and healthy control subjects. AB - OBJECTIVE: In type 1 diabetes the coexistence with other endocrine diseases and organ-specific autoantibodies has been frequently reported leading to the concept of autoimmune polyendocrine syndrome (APS). In addition, an association of type 1 diabetes with celiac disease has been described. These disorders share a similar genetic background, and first-degree relatives of type 1 diabetic patients may also be affected significantly. Screening for specific antibodies allows early diagnosis of these disorders. RESEARCH DESIGN AND METHODS: In the present cross sectional study, we analyzed sera from 197 recent-onset type 1 diabetic patients at the time of diagnosis, 882 first-degree relatives, and sera of 150 healthy control subjects for prevalence and co-occurence of the following antibodies (method): insulin autoantibodies (radioimmunoassay); GAD and IA-2 antibodies (radioligand assay); islet cell antibody, anti-adrenal cortex antibodies, and anti-gastric parietal cell antibodies (indirect immunofluorescence); anti thyroglobulin and anti-thyroid peroxidase antibodies; and gliadin IgG/A and tissue-transglutaminase IgA (enzyme-linked immunosorbent assay). RESULTS: The overall frequency of gastric patietal cell antibodies and adrenal antibodies did not differ significantly among groups. In contrast, type 1 diabetes-associated antibodies and thyroid antibodies were significantly more frequent both in recent onset type 1 diabetic patients and in the group of first-degree relatives (P < 0.05). The prevalence of gliadin IgG/IgA and transglutaminase IgA was significantly higher in the group of recent-onset type 1 diabetic patients (P < 0.05), but the difference between first-degree relatives and control subjects did not reach statistical significance. Focusing on the coexistence of antibodies, the group of recentonset type 1 diabetic patients presented with 27.4% of the subjects testing antibody-positive-specific for two or more of the envisaged disorders (i.e., type 1 diabetes, autoimmune thyroiditis, and celiac disease) compared with 3.1% in the group of first-degree relatives and 0 of 150 in the control population (P < 0.05). CONCLUSIONS: We conclude that, in an active case finding strategy, recent-onset type 1 diabetic patients should be routinely screened at least for concomitant autoimmune thyroid disease and additionally for celiac disease. Screening in their first-degree relatives should include at a minimum the search for thyroid autoimmunity in addition to screening for pre-type 1 diabetes. PMID- 11194236 TI - Early failure of the diabetic heart. PMID- 11194237 TI - MICA polymorphism is associated with type 1 diabetes in the Korean population. AB - OBJECTIVE: Recent studies have demonstrated that MICA (major histocompatibility complex class I chain-related genes) on the short arm of the chromosome 6 are associated with susceptibility to various autoimmune diseases in Caucasians. The aim of our study was to investigate the role of MICA in type 1 diabetes susceptibility independent of the HLA DR-DQ polymorphism in genetically distinct Koreans. RESEARCH DESIGN AND METHODS: A total of 119 patients selected from Korean Seoul type 1 diabetes registry and 134 nondiabetic unrelated control subjects were typed for exon 5 polymorphism of MICA in addition to HLA DR-DQ typing. A total of 52 simplex families of type 1 diabetes were also studied. RESULTS: The MICA microsatellite allele consisting of six repetitions of GCT/AGC (A6) was present at a significantly lower frequency in the diabetic patient group (Pc < 0.01; Pc = P value after Bonferroni correction) than in the control population. The MICA microsatellite allele consisting of four repetitions (A4) was present at a higher frequency in diabetic patients (P < 0.05). This deviated distribution was not changed even after controlling for the HLA DRB1-DQB1 haplotype. Transmission/disequilibrium test revealed significant deviation of transmission for alleles at the A6 polymorphism within the MICA gene (P < 0.05). CONCLUSIONS: We could assess that the MICA gene might be associated with type 1 diabetes transracially independent of the HLA gene. PMID- 11194238 TI - Abnormal glucose tolerance and increased risk for cardiovascular disease in Japanese-Americans with normal fasting glucose. AB - OBJECTIVE: To compare the American Diabetes Association (ADA) fasting glucose and the World Health Organization (WHO) oral glucose tolerance test (OGTT) criteria for diagnosing diabetes and detecting people at increased risk for cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS: Study subjects were 596 Japanese Americans. Fasting insulin, lipids, and C-peptide levels; systolic and diastolic blood pressures (BPs); BMI (kg/m2); and total and intra-abdominal body fat distribution by computed tomography (CT) were measured. Study subjects were categorized by ADA criteria as having normal fasting glucose (NFG), impaired fasting glucose (IFG), and diabetic fasting glucose and by WHO criteria for a 75 g OGTT as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetic glucose tolerance (DGT). RESULTS: Of 503 patients with NFG, 176 had IGT and 20 had DGT These patients had worse CVD risk factors than those with NGT . The mean values for NGT, IGT, and DGT, respectively, and analysis of covariance P values, adjusted for age and sex, are as follows; intra-abdominal fat area by CT 69.7, 95.0, and 101.1 cm2 (P < 0.0001); total CT fat area 437.7, 523.3, and 489.8 cm2 (P < 0.0001); fasting triglycerides 1.40, 1.77, and 1.74 mmol/l (P = 0.002); fasting HDL cholesterol 1.56, 1.50, and 1.49 mmol/l (P = 0.02); C-peptide 0.80, 0.90, 0.95 nmol/l (P = 0.002); systolic BP 124.9, 132.4, and 136.9 mmHg (P = 0.0035); diastolic BP 74.8, 77.7, and 78.2 mmHg (P = 0.01). CONCLUSIONS: NFG patients who had IGT or DGT had more intra-abdominal fat and total adiposity; higher insulin, C-peptide, and triglyceride levels; lower HDL cholesterol levels; and higher BPs than those with NGT. Classification by fasting glucose misses many Japanese-Americans with abnormal glucose tolerance and less favorable cardiovascular risk profiles. PMID- 11194240 TI - Diastolic dysfunction in normotensive men with well-controlled type 2 diabetes: importance of maneuvers in echocardiographic screening for preclinical diabetic cardiomyopathy. AB - OBJECTIVE: Because a pseudonormal pattern of ventricular filling has never been considered in studies that reported a prevalence of left ventricular diastolic dysfunction (LVDD) between 20 and 40%, our aim was to more completely evaluate the prevalence of LVDD in subjects with diabetes. RESEARCH DESIGN AND METHODS: We studied 46 men with type 2 diabetes who were aged 38-67 years; without evidence of diabetic complications, hypertension, coronary artery disease, congestive heart failure, or thyroid or overt renal disease; and with a maximal treadmill exercise test showing no ischemia. LVDD was evaluated by Doppler echocardiography, which included the use of the Valsalva maneuver and pulmonary venous recordings to unmask a pseudonormal pattern of left ventricular filling. RESULTS: LVDD was found in 28 subjects (60%), of whom 13 (28%) had a pseudonormal pattern of ventricular filling and 15 (32%) had impaired relaxation. Systolic function was normal in all subjects, and there was no correlation between LVDD and indexes of metabolic control. CONCLUSIONS: LVDD is much more common than previously reported in subjects with well-controlled type 2 diabetes who are free of clinically detectable heart disease. The high prevalence of this phenomenon in this high-risk population suggests that screening for LVDD in type 2 diabetes should include procedures such as the Valsalva maneuver and pulmonary venous recordings to unmask a pseudonormal pattern of ventricular filling. PMID- 11194239 TI - How cost-effective is the treatment of dyslipidemia in patients with diabetes but without cardiovascular disease? AB - OBJECTIVE: Epidemiological studies have shown that the risk of myocardial infarction (MI) in diabetic patients without cardiovascular disease (CVD) is comparable to the risk of MI in patients with CVD. We used a validated Markov model to compare the long-term costs and benefits of treating dyslipidemia in diabetic patients without CVD versus treating CVD patients without diabetes in the U.S. The generalizability and robustness of these results were also compared across six other countries (Canada, France, Germany, Italy, Spain, and the U.K.). RESEARCH DESIGN AND METHODS: With use of the Cardiovascular Disease Life Expectancy Model, cost effectiveness simulations of simvastatin treatment were performed for men and women who were 40-70 years of age and had dyslipidemia. We forecast the long-term risk reduction in CVD events after treatment. On the basis of the Scandinavian Simvastatin Survival Study results, we assumed a 35% reduction in LDL cholesterol and an 8% rise in HDL cholesterol. RESULTS: In the U.S., treatment with simvastatin for CVD patients without diabetes was cost effective, with estimates ranging from $8,799 to $21,628 per year of life saved (YOLS). Among diabetic individuals without CVD, lipid therapy also appeared to be cost-effective, with estimates ranging from $5,063 to $23,792 per YOLS. In the other countries studied, the cost effectiveness of treating diabetes in the absence of CVD was comparable to the cost effectiveness of treating CVD in the absence of diabetes. CONCLUSIONS: Among diabetic men and women who do not have CVD, lipid therapy is likely to be as effective and cost-effective as treating nondiabetic individuals with CVD. PMID- 11194241 TI - Potential short-term economic benefits of improved glycemic control: a managed care perspective. AB - OBJECTIVE: There are limited data relating glycemic control to medical costs among patients with diabetes. The goal of this study was to examine the potential impact of improved glycemic control on selected short-term complications of diabetes and associated costs in a managed care setting. RESEARCH DESIGN AND METHODS: Using a retrospective cohort design and automated databases from January 1994 to 30 June 1998, adult members of the Fallon Clinic who were diagnosed with diabetes were identified and assigned to one of three study groups based on each patient's mean HbA1c level: good control (<8%), fair control (8-10%), and poor control (> 10%) groups. Inpatient (hospital or skilled nursing facility) admissions for selected acute (short-term) complications, represented by selected infections, hyperglycemia, hypoglycemia, and electrolyte disturbances, and the associated medical charges were evaluated across the three HbA1c groups. Multivariate analyses were used to control for differences in several potential confounding factors among the study groups. All findings were expressed on a 3 year basis. RESULTS: Of 2,394 patients with diabetes, approximately 10% (251) had at least one inpatient stay for a short-term complication, accounting for 447 admissions. Over 3 years, the adjusted rate of inpatient treatment ranged from 13 per 100 patients with good glycemic control to 16 per 100 patients with fair glycemic control and 31 per 100 patients with poor glycemic control (P < 0.05). The corresponding mean adjusted charges were approximately $970, $1,380, and $3,040, respectively Among the 30% of the study population with long-term diabetic complications, the results were more marked; the adjusted admissions per 100 patients (mean charges) were estimated to be 30 ($2,610), 38 ($3,810), and 74 ($8,320) over 3 years for patients with an HbA1c of <8, 8-10, and > 10%, respectively. CONCLUSIONS: In typical practice, better glycemic control is associated with a reduced rate of admission for selected short-term complications and, therefore, reduced medical charges for these complications over a 3-year period. The potential short-term economic benefits are important to consider when making decisions regarding the adoption and use of new interventions for the management of diabetes. PMID- 11194242 TI - All-cause mortality in the Canterbury (New Zealand) insulin-treated Diabetic Registry population. AB - OBJECTIVE: To establish all-cause death rates and life expectancies of and risk factors for mortality in insulin-treated diabetic individuals living in Canterbury, New Zealand. RESEARCH DESIGN AND METHODS: Insulin-treated diabetic subjects (n = 1,008) on the Canterbury Diabetes Registry were tracked over 9 years, and their vital status was determined. Death rates were standardized using direct and indirect methods. Cox proportional hazard regression was used to model the effects of demographic and clinical covariates on survival time. RESULTS: At study entry, age ranged from 2.9 to 92.7 years, with mean 48.7 +/- 20.4 years; age at diagnosis was 0.2-88.9 years, mean 34.5 +/- 20.0 years; and duration of diabetes was 0.1-58.5 years, mean 14.0 +/- 10.6 years. There were 303 deaths in 7,372 person-years of follow-up with a standardized mortality ratio (SMR) of 2.6 (95% CI 2.4-3.0). Relative mortality was greatest for those aged 30-39 years (SMR 9.2 [4.8-16.2]). The death rate for the diabetic cohort standardized against the Segi world standard population was 16.2 per 1,000. Attained age, sex, and clinical subtype were significant predictors of mortality The SMR for subjects with type 1 diabetes and age at onset <30 years was 3.7 (CI 2.7-5.0), 2.2 (1.8 2.6) for those with onset > or =30 years, and 3.1 (2.5-3.7) for subjects suspected of having latent autoimmune diabetes in adulthood or insulin-treated type 2 diabetes. Life expectancy was reduced for both sexes at all ages. CONCLUSIONS: Mortality rates for insulin-treated diabetic individuals remain high, resulting in shortened life spans relative to the general population. Marked differences in mortality exist between clinical groups of subjects. Further research is needed to improve diabetes classification and to clarify differences in health outcomes. PMID- 11194243 TI - Impact of diabetes on employment and income in Manitoba, Canada. AB - OBJECTIVE: To compare employment and income of working-age (18-64 years) people with and without diabetes. RESEARCH DESIGN AND METHODS: We conducted a prospective population-based cohort study based in Manitoba, Canada, consisting of 25,554 individuals without diabetes and 608 with diabetes, of whom 242 had a complication of the disease. Adjusted odds ratios (ORs) of employment and income variables were determined. RESULTS: Diabetic individuals with complications were twice as likely not to be in the labor force (OR 2.07 [95% CI 1.49-2.87]) than nondiabetic individuals. This difference was not evident for diabetic individuals without complications (OR 1.20 [0.93-1.56]). Diabetic individuals without complications had incomes similar to those of nondiabetic individuals. The total income of diabetic individuals with complications was 72% of the income of nondiabetic individuals. When the analysis was limited to only those in the labor force, diabetic workers with complications still had only 85% the employment income of nondiabetic people. Diabetic individuals with complications received 58% more social support income. In a separate analysis of aboriginal individuals, complicated diabetes was not associated with an increased likelihood of not working or a decrease in employment income. CONCLUSIONS: In general, complications of diabetes and the absence of the disease affect the ability to earn income in Manitoba, Canada. This effect was not identified in the aboriginal population of the province. PMID- 11194244 TI - Efficacy, safety, and pump compatibility of insulin aspart used in continuous subcutaneous insulin infusion therapy in patients with type 1 diabetes. AB - OBJECTIVE: The purpose of this study was to compare the efficacy, safety and pump compatibility of insulin aspart (a rapid-acting insulin analog) and buffered regular human insulin in patients with type 1 diabetes undergoing continuous subcutaneous insulin infusion (CSII) therapy. RESEARCH DESIGN AND METHODS: This was a single-center randomized open-label study Patients received CSII therapy with insulin aspart (n = 19) or buffered regular human insulin (n = 10) for 7 weeks. Bolus doses of insulin aspart were administered immediately before meals and buffered regular human insulin 30 min before meals. RESULTS: Insulin aspart and buffered regular human insulin were both effective in controlling average daily blood glucose levels (8.2 +/- 1.9 and 8.5 +/- 2.1 mmol/l, respectively) (mean +/- SD) and maintaining serum fructosamine (343 +/- 25.7 and 336 +/- 27.4 micromol/l) and HbA1c (6.9 +/- 0.6 and 7.1 +/- 0.6%) levels. Possible obstructions and set leakages were infrequently reported in both groups. Similar numbers of patients experienced hypoglycemia (blood glucose <2.5 mmol/l): 14 (74%) insulin aspart patients versus 6 (60%) buffered regular human insulin patients. Patients receiving insulin aspart had fewer hypoglycemic events per patient (2.9) than those patients receiving buffered regular human insulin (6.2). There were no differences between the two insulins in the occurrence of hyperglycemic events (blood glucose >19 mmol/l) or in the number and type of adverse events. CONCLUSIONS: Insulin aspart and buffered regular human insulin were effective and well tolerated and provided similar pump compatibility when used in CSII therapy. PMID- 11194245 TI - Mealtime glucose regulation with nateglinide in healthy volunteers: comparison with repaglinide and placebo. AB - OBJECTIVE: This study was designed to compare the pharmacodynamic effects of single doses of nateglinide (A-4166), repaglinide, and placebo on mealtime insulin secretion and glycemic control in healthy subjects. RESEARCH DESIGN AND METHODS: Fifteen healthy volunteers participated in this open-label five-period crossover study. They received single 10-min preprandial doses of 120 mg nateglinide, 0.5 or 2 mg repaglinide, or placebo or 1 min preprandially of 2 mg repaglinide. Subjects received each dose only once, 48 h apart. Pharmacodynamic and pharmacokinetic assessments were performed from 0 to 12 h postdose. RESULTS: Nateglinide induced insulin secretion more rapidly than 2 and 0.5 mg repaglinide and placebo (10 min preprandial), with mean rates of insulin rise of 2.3, 1.3, 1.15, and 0.8 microU x ml(-1) x min(-1), respectively, over the 0- to 30-min postmeal interval. After peaking, insulin concentrations decreased rapidly in the nateglinide-treated group and were similar to placebo within 2 h postdose. After 2 mg repaglinide, peak insulin concentrations were delayed and returned to baseline more slowly than with nateglinide treatment. Nateglinide treatment produced lower average plasma glucose concentrations in the 0- to 2-h postdose interval than either dose of repaglinide and placebo (P < 0.05 vs. 0.5 mg repaglinide and placebo). Plasma glucose concentrations returned more rapidly to predose levels with nateglinide treatment than with either dose of repaglinide. Treatment with repaglinide produced a sustained hypoglycemic effect up to 6 h postdose. CONCLUSIONS: In this single-dose study in nondiabetic volunteers, nateglinide provided a more rapid and shorter-lived stimulation of insulin secretion than repaglinide, resulting in lower meal-related glucose excursions. If similar results are observed in diabetes, nateglinide may produce a more physiological insulin secretory response with the potential for a reduced risk of postabsorptive hypoglycemia. PMID- 11194246 TI - New ulceration, new major amputation, and survival rates in diabetic subjects hospitalized for foot ulceration from 1990 to 1993: a 6.5-year follow-up. AB - OBJECTIVE: To evaluate 1) the new ulceration, the new major amputation, and the survival rates of 115 diabetic subjects hospitalized for foot ulceration from 1990 to 1993, with an average follow-up of 6.5 years, and 2) the demographic and clinical characteristics associated with these events. RESEARCH DESIGN AND METHODS: A total of 115 subjects, 31 women and 84 men, were monitored until 31 December 1998. All subjects were provided with therapeutic shoes and received intense education. Data concerning new ulceration, new major amputation, and reamputation events and the date and cause of death were recorded for each patient. The prognostic factors for these events were then evaluated. RESULTS: The average follow-up was 78.3 +/- 15.3 months (range 60-106). During this time, 13 homolateral and 12 contralateral episodes of new ulceration occurred. At univariate analysis, none of the variables considered were significantly associated with the new ulceration. There were three major amputations: two of the limb previously healed and one of the contralateral limb. Of the 115 subjects, 51 (44.3%) died: 24 of the 31 women (77.4%) and 27 of the 84 men (32.1%). Ischemic cardiopathy was the most frequent cause of death (60.8%). Mortality concerned 20 of the 27 subjects (74.1%) undergoing major amputation from 1990 to 1993 and 31 of the 88 healed subjects (35.2%), with a significant difference (P < 0.0001). Multivariate analysis showed the independent role of the ankle-brachial index < or =0.5 (P = 0.005), age (P = 0.003), and female sex (P = 0.027). CONCLUSIONS: We believe that the use of therapeutic shoes and intense educational training, including the education of the family, have contributed to the low incidence of new ulceration and major amputation in our study population. The high frequency of ischemic cardiopathy as a cause of death should, perhaps, lead to a more aggressive diagnostic and therapeutic attitude toward this pathology in diabetic subjects admitted to hospitals for foot ulceration. PMID- 11194247 TI - A comparison of two diabetic foot ulcer classification systems: the Wagner and the University of Texas wound classification systems. AB - OBJECTIVE: In this study the following two ulcer classification systems were applied to new foot ulcers to compare them as predictors of outcome: the Wagner (grade) and the University of Texas (LT) (grade and stage) wound classification systems. RESEARCH DESIGN AND METHODS: Ulcer size, appearance, clinical evidence of infection, ischemia, and neuropathy at presentation were recorded, and patients were followed up until healing or for 6 months. RESULTS: Of 194 patients with new foot ulcers, 67.0% were neuropathic, 26.3% were neuroischemic, 1.0% were ischemic, and 5.7% had no identified underlying factors. Median (interquartile range [IQR]) ulcer size at presentation was 1.5 cm2 (0.6-4.0). Lower-limb amputations were performed for 15% of ulcers, whereas 65% healed [median (IQR) healing time 5 (3-10) weeks] and 16% were not healed at study termination; 4% of patients died. Wagner grade (P < 0.0001), and UT grade (P < 0.0001) and stage (P < 0.001) showed positive trends with increased number of amputations. For UT stage, the risk of amputation increased with infection both alone (odds ratio [OR] = 11.1, P < 0.0001) and in combination with ischemia (OR = 14.7, P < 0.0001), but not significantly with ischemia alone (OR = 4.6, P = 0.09). Healing times were not significantly different for each grade of the Wagner (P = 0.1) or the UT system (P = 0.07), but there was a significant stepwise increase in healing time with each stage of the UT system (P < 0.05), and stage predicted healing (P < 0.05). CONCLUSIONS: Increasing stage, regardless of grade, is associated with increased risk of amputation and prolonged ulcer healing time. The UT system's inclusion of stage makes it a better predictor of outcome. PMID- 11194248 TI - Insulin resistance and insulin secretory dysfunction are independent predictors of worsening of glucose tolerance during each stage of type 2 diabetes development. AB - OBJECTIVE: Although prospective studies indicate that insulin resistance and insulin secretory dysfunction predict type 2 diabetes, they provide limited information on the relative contributions of both abnormalities to worsening glucose tolerance at different developmental stages of the disease. We therefore assessed the predictive effect of insulin resistance and insulin secretory dysfunction separately for the progression from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) and from IGT to diabetes. RESEARCH DESIGN AND METHODS: Insulin-stimulated glucose disposal (M) (hyperinsulinemic clamp), acute insulin secretory response (AIR) (25-g intravenous glucose tolerance test), and body composition (hydrodensitometry or dual-energy X-ray absorptiometry) were measured in 254 Pima Indians with NGT and in 145 Pima Indians with IGT, who were then followed for 0.5-13 years. RESULTS: After follow-ups of 4.4 +/- 3.1 and 5.5 +/- 3.4 years, 79 (31%) of the subjects with initial NGT had developed IGT, and 64 (44%) of the subjects with initial IGT had developed diabetes. In proportional hazards analyses with adjustment for age, sex, and percent body fat, low M and low AIR were independent predictors of both the progression from NGT to IGT (relative hazards [95% CI] for 10th vs. 90th percentile: M 2.4 [1.2-4.7], P < 0.02; AIR 2.1 [1.1-4.1], P < 0.04) and from IGT to diabetes (M 2.5 [1.3-5.0], P < 0.01; AIR 1.8 [0.99-3.3], P = 0.055). CONCLUSIONS: During each stage of the development of type 2 diabetes, insulin resistance and insulin secretory dysfunction are independent predictors of worsening glucose tolerance and are, therefore, both targets for the primary prevention of the disease. PMID- 11194249 TI - Limited joint mobility in type 1 diabetic patients: associations with microangiopathy and subclinical macroangiopathy are different in men and women. AB - OBJECTIVE: To study the relationship of limited joint mobility (LJM) in type 1 diabetic patients with microvascular complications, hypertension, and early atherosclerosis and to determine whether sex has an influence on possible associations. RESEARCH DESIGN AND METHODS: A total of 335 consecutive unselected patients (191 women and 144 men), aged 14-40 years, were studied for LJM, retinopathy, nephropathy (stages III and IV), and hypertension. Standard laboratory tests were performed; the intima-media thickness (IMT) of the carotid arteries, which reflects the extent of early atherosclerosis, was measured by high-resolution ultrasound, and plaques were identified. RESULTS: The frequency of LJM was 33.7% (29.8% in women and 38.9% in men). Subjects with LJM had a longer diabetes duration (P < 0.001) than those without (women 16.7 +/- 9.1 vs. 10.3 +/- 6.0 years; men 15.0 +/- 9.0 vs. 9.4 +/- 6.3 years). Age, HbA1c, lipids, and systolic/diastolic blood pressure were not different between men and women with or without LJM. Men with LJM had a higher albumin excretion rate (37.1 vs. 13.1 microg/min, P < 0.05) than those without LJM and showed a higher risk of proteinuria (odds ratio 1.8, 95% CI 1.2-2.7; P < 0.05), retinopathy (2.4, 1.7 3.5; P < 0.001), and hypertension (1.7, 1.2-2.6; P < 0.05). The occurrence of these complications was not different between women with and without LJM, but only women with LJM had a greater IMT (0.59 +/- 0.13 vs. 0.55 +/- 0.10 mm, P < 0.05) and a higher risk of plaques (odds ratio 2.1, 95% CI 1.3-3.4; P < 0.05) than women without LJM. In a multiple logistic regression analysis, adjusted for age and diabetes duration, male sex independently predicted the presence of LJM. Moreover, LJM proved to be an independent predictor of retinopathy in men only. CONCLUSIONS: LJM is an indicator of microvascular disease in men, and LJM is associated with early macrovascular disease in women. PMID- 11194250 TI - Inability of five-month-old infants to retrieve a contiguous object: a failure of conceptual understanding or of control of action? AB - Infants of 5 to 6 months of age can retrieve a free-standing object, but fail to retrieve the same object from atop a slightly larger object. The accepted explanation has been that the infants do not understand that an object continues to exist independently when placed upon another. Predictions based on that explanation were tested against the hypothesis that infants' problem consists of lack of precision in visually guided reaching and lack of ability to inhibit reflexive reactions to touch. Twelve infants each at 5 and 7 months of age were tested on 16 trials. More 5-month-olds succeeded, in less time, and with fewer touches to an edge of the base, on trials more forgiving of an imprecise reach than on less forgiving trials. Success in retrieving objects close in size and fully contiguous with their bases was seen even at 5 months when the demands on skill in reaching were reduced. It is proposed that when 5-month-old infants fail to retrieve one object placed upon another, it is not because of a lack of conceptual understanding, but because they lack the skill to reach to the top object without accidentally touching an edge of the base en route. PMID- 11194251 TI - Middle-school-age outcomes in children with very low birthweight. AB - Most previous studies of children with birthweight <750 g have focused on early childhood sequelae. To evaluate later outcomes, a regional sample of 60 <750-g birthweight children was compared at middle school age (M = 11 years) to 55 children with birthweight 750-1,499 g and 49 term controls. The groups were matched on age, gender, and demographic variables at the time of an early-school age assessment (mean age 7 years). The <750-g birthweight group fared less well at middle school age than the term group on measures of cognitive function, achievement, behavior, and academic performance. In many instances, outcomes were less favorable for the <750-g children than for the 750 to 1,499-g group. Children in the <750-g group who were free of neurosensory disorders and global cognitive impairment performed more poorly on several tests than their term counterparts. Group differences in this subsample on tests of motor skills, math, and the ability to copy and recall a complex drawing remained significant even after controlling for IQ. Disparities between the <750-g and term groups increased with age for some measures. Despite favorable outcomes for many children in the <750-g group, this population is at risk for long-term developmental problems. PMID- 11194252 TI - Sibling differentiation in adolescence: implications for behavioral genetic theory. AB - The presence of sibling "differentiating processes"--defined as processes in which increased sibling similarity in environmental or genetic factors leads to differences in sibling outcomes-poses a challenge for standard behavioral genetic theory and research. The presence of differentiation processes may affect estimates of genetic and environmental parameters in ways that have not been fully recognized. Utilizing data from the Nonshared Environment and Adolescent Development project, this study examined whether differentiating processes existed for seven composite indices of positive and negative adolescent adjustment. The 720 sibling pairs in the study were broken down into groups by age difference (0-4 years) between siblings. The hypothesis that siblings close in age would demonstrate lower correlations on adjustment measures was generally supported at two time points, three years apart. However, siblings one year apart at Time 1 were more similar to each other than were siblings two years apart, suggesting that shared environmental influences counteract sibling differentiation processes for these siblings. The overall trend supporting sibling differentiation was found to be unrelated to measures of sibling positivity and negativity. PMID- 11194253 TI - Can young infants add and subtract? AB - Three experiments (N = 68), using Wynn's procedure, tested 5-month-old infants' looking time reactions to correct and incorrect results of simple addition and subtraction transformations. The aim was to investigate both the robustness and the parameters of infants' arithmetic competence. Experiments 1 and 2 (N = 44) were replications of Wynn's first two experiments in which infants were shown addition (1 + 1 = 1 or 2) and subtraction (2 - 1 = 1 or 2) requiring imprecise calculation. Experiment 3 (N = 24) was a subtraction counterpart (3 - 1 = 1 or 2) to Wynn's third experiment requiring precise calculation of addition (1 + 1 = 2 or 3). Unlike Wynn, we found no systematic evidence of either imprecise or precise adding and subtracting in young infants. Our results, together with the mix of both positive and negative findings from other studies of infant arithmetic, suggest that infants' reactions to displays of adding and subtracting are variable and, therefore, that infants' numerical competencies are not robust. This conclusion is consistent with previous findings indicating that simple adding and subtracting develops gradually and continuously throughout infancy and early childhood. PMID- 11194254 TI - Findings of addition and subtraction in infants are robust and consistent: reply to Wakeley, Rivera, and Langer. AB - Findings showing numerical computation abilities in infants are considerably more robust and consistent than Wakeley, Rivera, and Langer suggest. All the interim replication attempts have successfully replicated my original findings. Possible reasons for Wakeley et al.'s failure to replicate are discussed. PMID- 11194255 TI - Predicting the outcomes of physical events: two-year-olds fail to reveal knowledge of solidity and support. AB - Two-year-olds' (N = 153) knowledge of solidity was tested in four search tasks adapted from infant looking-time experiments. In Experiment 1, 2-year-olds failed to search in the correct location for a falling ball after a hidden shelf that blocked its trajectory had been inserted in the apparatus. Experiment 2 extended this finding by showing that 2-year-olds failed to take into account the effects of either removing or inserting a shelf in their search for a toy dropped behind a screen. Experiment 3 examined sensitivity to the constraint provided by a solid barrier on horizontal motion. In all three experiments, 2-year-old children searched initially at the location where they saw the object during familiarization. Experiment 4, using multiple test trials but no familiarization to a pretest location, also showed that 2-year-olds failed to take the presence or absence of a barrier into account when planning where to search for a toy they had seen dropped behind a screen. In all of these studies, 2-year-olds showed no evidence of representing solidity and support constraints on the trajectories of falling objects. Experiments 1 and 3 also included 2 1/2-year-olds (N = 31), who succeeded on these search tasks. The implications of the poor performance of 2 year-olds, in the face of success by very young infants on looking-time measures of sensitivity to similar constraints on object motion, are discussed. PMID- 11194256 TI - Children's attention to rigid and deformable shape in naming and non-naming tasks. AB - In four experiments with three-year-olds (N = 67), we investigate children's understanding of the differential importance of shape for categorization of solid rigid objects with fixed shapes and solid but deformable objects with shapes that can be changed. In a non-naming task we find that young children categorize rigid and deformable things differently and know that material is important for deformable things and shape for rigid things. In two naming tasks, however, children generalize names for both solid and deformable objects by shape similarity and disregard rigidity. To understand this pattern of results we examine a corpus of early-learned nouns and the kinds of rigid and nonrigid things named by nouns in that corpus. The results suggest that names for categories of solid, rigid objects in which instances are similar in shape dominate children's early noun vocabularies. We suggest that children's novel word generalizations for deformable things may be overgeneralizations of this dominant pattern. PMID- 11194257 TI - Word-learning skills of deaf preschoolers: the development of novel mapping and rapid word-learning strategies. AB - Word-learning skills of 19 deaf/hard-of-hearing preschoolers were assessed by observing their ability to learn new words in two contexts. The first context required the use of a novel mapping strategy (i.e., making the inference that a novel word refers to a novel object) to learn the new words. The second context assessed the ability to learn new words after minimal exposure when reference was explicitly established. The children displayed three levels of word-learning skills. Eleven children learned words in both contexts. Five were able to learn new words rapidly only when reference was explicitly established. Two children did not learn new words rapidly in either context. The latter seven children were followed longitudinally. All children eventually acquired the ability to learn new words in both contexts. The deaf children's word-learning abilities were related to the size of their vocabularies. The present study suggests that word learning strategies are acquired even when children are severely delayed in their language development and they learn language in an atypical environment. PMID- 11194258 TI - Effects of age and delay on the amount of information provided by alleged sex abuse victims in investigative interviews. AB - A total of 145 children of 4 to 5, 6 to 7, 8 to 9, and 10 to 12 years of age were interviewed within 3 days, 1 month, 1 to 3 months, or 5 to 14 months after allegedly experiencing a single incident of sexual abuse. The proportion of substantive investigative utterances eliciting new details from the children increased with age and decreased after delays of more than 1 month. Age (but not delay) was also associated with the length and richness of informative responses to individual investigative utterances of all types. Children were more likely to provide new details in response to option-posing and suggestive prompts. As in previous field studies, interviewers employed few open-ended prompts, and thus only 5% of the information obtained was elicited using free-recall prompts. PMID- 11194259 TI - Adolescents sex-typed friendship experiences: does having a sister versus a brother matter? AB - This study examines the connections between having a sister versus a brother and coming from a same-sex versus an opposite-sex sibling dyad and the degree of sex typing in adolescents' friendship experiences, including the qualities of their friendships (i.e., intimacy, control) and their friends' personal attributes (i.e., sex-typed leisure interests, expressive and instrumental personality qualities). Participants were 159 firstborn-secondborn adolescent sibling pairs (M = 14.94 years and M = 12.43 years, respectively) and a close friend of each sibling (N = 636, including siblings and friends). Data were collected during home visits with siblings and telephone interviews with friends of siblings. The results suggested that sisters may learn control tactics from their brothers that they apply in their friendships; boys, however, were less likely to model the emotional intimacy that characterized their sisters' experiences with friends. In addition, coming from an opposite-sex sibling dyad was linked to sex-typing in friends' personal attributes, particularly their masculine leisure interests and instrumental personality qualities. Sisters and brothers may provide unique opportunities to learn about sex-typed relationship experiences in early adolescence, a time when gender segregation in the peer context is pervasive. PMID- 11194260 TI - Sibling comparison of differential parental treatment in adolescence: gender, self-esteem, and emotionality as mediators of the parenting-adjustment association. AB - This study employs findings from social comparison research to investigate adolescents' comparisons with siblings with regard to parental treatment. The sibling comparison hypothesis was tested on a sample of 516 two-child families by examining whether gender, self-esteem, and emotionality-which have been found in previous research to moderate social comparison-also moderate sibling comparison as reflected by siblings' own evaluations of differential parental treatment. Results supported a moderating effect for self-esteem and emotionality but not gender. The sibling comparison process was further examined by using a structural equation model in which parenting toward each child was associated with the adjustment of that child and of the child's sibling. Evidence of the "sibling barricade" effect-that is, parenting toward one child being linked with opposite results on the child's sibling as on the target child-was found in a limited number of cases and interpreted as reflecting a sibling comparison process. For older siblings, emotionality and self-esteem moderated the sibling barricade effect but in the opposite direction as predicted. Results are discussed in terms of older siblings' increased sensitivity to parenting as well as the report of differential parenting reflecting the child's level of comfort and benign understanding of differential parenting, which buffers the child against environmental vicissitudes evoking sibling comparison processes. PMID- 11194261 TI - Mothers of anxious/ambivalent infants: maternal characteristics and child-care context. AB - A general model of the determinants of parenting was employed to explore the antecedents of the ambivalent attachment pattern in Israel. Specifically, three classes of variables were identified: maternal, infant, and child-care context. Participants were 98 mothers and their infants. This research was part of a longitudinal study on sleep patterns. Mothers filled out questionnaires and were observed with their infants in the Ainsworth Strange Situation laboratory procedure. Mothers of ambivalent infants showed lower education level, higher separation anxiety, and higher parenting stress than mothers of secure infants. Infants' perceived difficult temperament did not discriminate between the two groups. Longer hours spent at work and placement in group day-care were both associated with ambivalent attachment. The findings are discussed in light of the importance of considering distal factors such as maternal attitudes and general caregiving strategy in clarifying the antecedents of attachment patterns. PMID- 11194262 TI - Maternal regulation of sibling interactions in the preschool years: observational study in Japanese families. AB - Characteristics of three maternal regulating behaviors--(1) reference to one sibling's actions or emotional states toward the other sibling, (2) encouragement of sibling interactions, (3) distraction of one sibling's attention away from the other sibling-and their associations with children's positive and negative behaviors toward their siblings were investigated through semistructured home observations for 40 sibling pairs (1-4 years, 2-8 years) and their mothers in Japanese families. Maternal regulating behaviors were observed more frequently when the younger sibling was still in an early developmental stage in the preschool years, although the findings were modest. The older sibling's negative behaviors toward the younger sibling positively correlated with maternal distraction toward the younger; alternatively, the younger sibling's negative behaviors do not correlate with maternal distraction but do correlate with maternal encouragement directed toward the older sibling. Reliable associations were found between maternal regulating behaviors and prosocial exchanges between siblings; maternal reference to the younger sibling's actions or emotional states directed toward the older sibling was associated with the older sibling's positive behavior toward the younger sibling. Maternal regulating behaviors during mother-sibling triadic interactions were associated with the quality of sibling relationships. PMID- 11194263 TI - Interparental conflict and child adjustment: testing the mediational role of appraisals in the cognitive-contextual framework. AB - Children's appraisals of interparental conflict consistently have been associated with adjustment problems, but the processes that give rise to this association are not well understood. This paper proposes that appraisals of threat and self blame mediate the association between children's reports of interparental conflict and internalizing problems, and tests this mediational hypothesis in two samples of children, one drawn from the community (317 ten- to fourteen-year olds) and the other from battered women's shelters (145 ten- to twelve-year olds). Results indicate that perceived threat mediates the association between interparental conflict and internalizing problems for boys and girls in both samples, and self-blame mediates this association for boys in both samples and girls in the shelter sample. Perceived threat and self-blame do not mediate links with externalizing problems, and there is no evidence of a moderating effect of appraisals on the association between conflict and child adjustment. Implications for understanding the mechanism by which exposure to interparental conflict could lead to child maladjustment are discussed. PMID- 11194264 TI - Agents of change: pathways through which mentoring relationships influence adolescents' academic adjustment. AB - A conceptual model was tested in which the effects of mentoring relationships on adolescents' academic outcomes were hypothesized to be mediated partially through improvements in parental relationships. The parameters of the model were compared with those of an alternative, in which improved parental relationships were treated as an outcome variable rather than a mediator. The study included 959 young adolescents (M age = 12.25 years), all of whom applied to Big Brothers Big Sisters programs. The adolescents were randomly assigned to either the treatment or control group and administered questions at baseline and 18 months later. The hypothesized model provided a significantly better explanation of the data than the alternative. In addition to improvements in parental relationships, mentoring led to reductions in unexcused absences and improvements in perceived scholastic competence. Direct effects of mentoring on global self-worth, school value, and grades were not detected but were instead mediated through improved parental relationships and scholastic competence. Implications of the findings for theory and research are discussed. PMID- 11194265 TI - Middle-class African American adolescents' and parents' conceptions of parental authority and parenting practices: a longitudinal investigation. AB - Conceptions of parental authority and ratings of parental rules and decision making were examined longitudinally among 82 middle-class African American adolescents and their parents (82 mothers and 52 fathers), who were divided into two groups according to family income. Adolescents were, on average, 13.14 years of age at Time 1 and 15.05 years of age at Time 2. Nearly all adolescents and parents affirmed parents' legitimate authority to regulate (and children's obligation to comply with) rules regarding moral, conventional, prudential, friendship, and multifaceted issues, but they were more equivocal in their judgments regarding personal issues. With age, adolescents increasingly judged personal issues to be beyond the bounds of legitimate parental authority, but judgments differed by family income. Adolescents from upper income families rejected parents' legitimate authority to regulate personal issues more at Time 1 than did adolescents from middle income families, but no differences were found at Time 2. Authority to regulate adolescents' behavior did not extend to other adults or to schools, churches, and the law. With adolescents' increasing age, African American families became less restrictive in regulating prudential, friendship, multifaceted, and personal issues. Adolescents', mothers', and fathers' judgments demonstrated significant continuity over time, but few cross- or within-generation associations in judgments were found. Conceptions of legitimate parental authority at Time 1 were found to predict family rules at Time 2. PMID- 11194267 TI - [Federal committees wnat uniform continuing education certification. MMW readers will soon be able to earn federally valid continuing education points]. PMID- 11194268 TI - [Drug therapy of backache. "We must distance ourselves from these guidelines"]. PMID- 11194266 TI - Child development and evolutionary psychology. AB - Evolutionary developmental psychology involves the expression of evolved, epigenetic programs, as described by the developmental systems approach, over the course of ontogeny. There have been different selection pressures on organisms at different times in ontogeny, and some characteristics of infants and children were selected in evolution to serve an adaptive function at that time in their life history rather than to prepare individuals for later adulthood. Examples of such adaptive functions of immaturity are provided from infancy, play, and cognitive development. Most evolved psychological mechanisms are proposed to be domain specific in nature and have been identified for various aspects of children's cognitive and social development, most notably for the acquisition of language and for theory of mind. Differences in the quality and quantity of parental investment affect children's development and influence their subsequent reproductive and childcare strategies. Some sex differences observed in childhood, particularly as expressed during play, are seen as antecedents and preparations for adult sex differences. Because evolved mechanisms were adaptive to ancestral environments, they are not always adaptive for contemporary people, and this mismatch of evolved mechanisms with modern environments is seen in children's maladjustment to some aspects of formal schooling. We argue that an evolutionary perspective can be valuable for developing a better understanding of human ontogeny in contemporary society and that a developmental perspective is important for a better understanding of evolutionary psychology. PMID- 11194269 TI - [Not just tolerating chronic pain. Which analgesics for elderly patients?]. AB - Some 25-50% of all elderly persons living at home suffer from chronic pain. Among nursing home residents, the figures are appreciably higher, ranging between 45% and 80%. The major causes of pain in old age are degenerative joint disease, lower back pain, cancer, osteoporosis and herpes zoster, polymyalgia rheumatica, and arterial occlusive disease. In many cases, chronic pain goes undiagnosed and is not properly treated. When a correct diagnosis is established, however, it is almost always possible to achieve adequate pain relief by a combination of non drug treatment and analgesics, and thus to improve the patient's quality of life. PMID- 11194270 TI - [Acute confusion in the elderly. Search for etiology and therapy]. PMID- 11194271 TI - [Suicidality in the elderly. What to do when the patient is suicidal?]. AB - The suicide rate shows a constant increase with age, and the reasons are multifactorial. In particular people with mental disturbances, especially depression, age-related multimorbidity and loneliness, have a tendency towards suicidal behavior. Therapeutic approaches are grounded in the early recognition of direct and indirect remarks indicative of suicidal tendencies, and in binding agreements on necessary therapeutic measures. For the future, there is an urgent need for further expansion of the cooperative effort between physicians and care providing and social services in multiprofessional teams that also involve relatives, together with training in crisis intervention in suicidal persons. PMID- 11194272 TI - [It's never too late to build muscle. How the elderly benefit from power training]. PMID- 11194273 TI - [What to recommend and prescribe. When children have headaches]. PMID- 11194274 TI - [Therapy control in respiratory tract diseases. Diagnostic series: evaluating lung function]. PMID- 11194275 TI - [Antidepressive drug against nicotine. A method for smoking cessation]. AB - Currently, two drugs are considered useful for those wishing to quit smoking in Germany--nicotine and bupropion. The mechanism of action appears to involve reuptake inhibition of the transmitters noradrenaline and/or dopamine by the brain. Treatment with a daily dose of 300 mg delayed release buproplon for 7 to 9 weeks resulted in smoking cessation in 30.3% (buproplon) and 35.5% (bupropion plus nicotine patch) of the smokers at 12 months (placebo: 15.6%, nicotine patch: 16.4%). A large number of the participants had had negative experience with nicotine preparations in previous attempts to stop smoking. Most side effects of bupropion involve the nervous system (disturbed sleep, trembling, loss of concentration, headache, dizziness, depression, restlessness, anxiety) and the gastrointestinal tract (dry mouth, nausea, vomiting, abdominal pain, constipation) and elevated temperature (> 1% of the treated subjects). It is suggested that, at present, bupropion should be used for this indication only in those smokers in whom treatment with nicotine has failed. PMID- 11194276 TI - [Diagnostic quiz. Tachycardia in lung disease. Sarcoidosis]. PMID- 11194277 TI - [Drug therapy and prevention on unreliable footing. Stepchildren of migraine research]. PMID- 11194278 TI - [The Netherlands permit active euthanasia. Physician as the angel of death? (interview by Dr. med. Julia Rautenstrauch)]. PMID- 11194279 TI - [14. Coronary heart diseases: how the general practitioner can improve the prognosis]. PMID- 11194280 TI - Influence of peripheral vascular occlusive disease on the morbidity and mortality of coronary artery bypass grafting. AB - The impact of peripheral vascular occlusive disease (PVD) on outcome for patients who have undergone coronary artery bypass grafting (CABG) was assessed by comparing preoperative and intraoperative patient characteristics and outcome in 2 groups of patients who underwent CABG (patients with PVD, n=96; patients without PVD, n=593). Patients with PVD were significantly older (69+/-8.4 vs 63+/ 8.7; p<0.0001), and had a higher incidence of diabetes mellitus (48% vs 32%; p<0.01), hypertension (62% vs 46%; p<0.01), preoperative cerebral infarction (26% vs 12%; p<0.001) and chronic renal dysfunction (11% vs 4.4%; p<0.01) than those without PVD. Postoperative morbidity and mortality were assessed, after those risk factors were adjusted, using multivariate logistic regression analysis. The perioperative myocardial infarction (PMI) rate and in-hospital mortality rate were significantly higher in patients with PVD than in patients without PVD (9.4% vs 3.0%; p=0.0108, 17% vs 2.7%; p=0.0003, respectively). The odds ratio of PMI and in-hospital mortality were 3.4 (95% confidence intervals (CI): 1.3-8.6) and 4.3 (95% CI: 2.0-9.5), respectively. Although the excess mortality rate was mainly the result of cardiac problems, such as low output syndrome or arrhythmia, in most of the cases, PVD, which may frequently prevent the use of the intraaortic balloon pump, also seemed to have a strong relation to postoperative morbidity and mortality. PMID- 11194281 TI - Extremely thickened media of small pulmonary arteries in fatal pulmonary hypertension with congenital heart disease--a morphometric and clinicopathological study. AB - There are patients with congenital heart disease and fatal pulmonary hypertension in whom the medial hypertrophy of the small pulmonary arteries is quite beyond the extent of ordinary cases of hypertension, a condition described as pulmonary hypertension with extremely thickened media of small pulmonary arteries (PH/ETM). Lungs from 6 infants, all younger than 2 years of age, who had congenital heart disease and fatal pulmonary hypertension, were analyzed by accurately measuring the media using Suwa's method. In PH/ETM, the media of the small pulmonary arteries was shown to be not only unusually thick, but extending toward the periphery, whereas the intimal changes were unexpectedly mild. In the PH/ETM group, the % wall thickness at a diameter of 50 microm (%Tw(50)), determined from regression analysis, was 23.2+/-1.3%, which was significantly higher than in either the control (10.3+/-1.2%) or ventricular septal defect group (18.9+/ 1.6%). In persistent pulmonary hypertension of the newborn (PPHN), it was 22.3+/ 1.8%, not significantly different from PH/ETM. The striking medial hypertrophy in PH/ETM and PPHN was apparently confined to small pulmonary arteries and in both conditions is likely to be the result of maldevelopment of these arteries. Surgical intervention may trigger a critical elevation of the pulmonary arterial resistance. PMID- 11194283 TI - Determination of left ventricular mass by echocardiography in normotensive diabetic patients. AB - Patients with Type 2 diabetes mellitus (DM) have excessive cardiovascular morbidity and mortality, even in the absence of hypertension. Left ventricular hypertrophy (LVH), which is an ominous prognostic sign and an independent risk factor for cardiac events, is often present in Type 2 DM patients. Forty-two Type 2 DM patients without hypertension, all of whom had been diagnosed more than 10 years ago, were examined in the present study. They had no evidence of renal dysfunction and had not received any anti-hypertensive drugs. Age-matched healthy normal subjects (n=47) were recruited as controls. All participants were classified according to the left ventricular mass index (LVMI) using M-mode echocardiography and their systolic function (fractional shortening) was examined. The systolic function was not significantly different between the Type 2 DM and control groups. LVH can be seen even in the normotensive Type 2 DM patients, with these patients still having a higher LVMI than the normal control subjects. Although the plasma insulin levels were not significantly increased in the Type 2 DM patients, the LVMI significantly correlated with plasma insulin levels. However, the LVMI did not significantly correlate with plasma fasting glucose and hemoglobin A1c in the Type 2 DM patients. These results suggest that LVH in Type 2 DM patients without hypertension may be associated with elevated plasma insulin levels. PMID- 11194282 TI - Prognostic significance of cardiopulmonary exercise testing for 10-year survival in patients with mild to moderate heart failure. AB - Although a number of studies have investigated the prognostic significance of exercise variables, they have focused only on short-term prognosis in relatively severe heart failure. This study was carried out to determine whether the indices obtained during cardiopulmonary exercise testing have prognostic significance during a 10-year follow-up in mild to moderate heart failure. Three hundred and sixty-four consecutive patients with cardiac disease performed 4 min of 20-W warm up, followed by a symptom-limited incremental exercise test on a cycle ergometer. In addition to the measurements of peak oxygen uptake (VO2) and gas exchange (anaerobic) threshold, the time constant of VO2 kinetics during the onset of warm up exercise was calculated using a single exponential equation. Data on mortality were available for follow-up in 260 patients. After 3,331+/-610 days of follow up, 29 cardiovascular-related deaths occurred. The time constant of VO2 in the nonsurvivors was 76.7+/-43.3 s and was significantly prolonged compared with that of survivors (55.3+/-30.6 s, p=0.001). Peak VO2 and gas exchange threshold were both significantly lower in nonsurvivors than in survivors. Kaplan-Meier survival curves for 10 years of follow-up demonstrated a survival rate of 89.0% for patients with a normal VO2 time constant (< 80 s) and 71.7% for those with a longer time constant (> or = 80 s), showing a significant difference in survival (p=0.0028). Respiratory gas parameters obtained during exercise testing, particularly the time constant of VO2 kinetics, were found to be useful for predicting long-term prognosis in patients with chronic heart failure. These results suggest that cardiopulmonary exercise testing could be more applicable in ambulatory patients with minimal symptoms or minimal functional impairment. PMID- 11194284 TI - Causes of late mortality in patients with disabling intermittent claudication. AB - The long-term prognosis of patients suffering from intermittent ischemic claudication is reportedly worse than that of the normal population. The outcome of patients with ischemic claudication admitted to hospital was reviewed retrospectively to identify the causes of late death. The cumulative survival rates for patients with claudication were 94.6% at 1 year, 79.4% at 3 years, 67.3% at 5 years and 37.4% at 10 years. The 3 major causes of death, that is, ischemic heart disease, malignancy, and cerebrovascular accident, were equally common. The younger patients tended to die of ischemic heart disease, whereas the older patients died of cerebrovascular accidents. Malignancies caused a similar number of late deaths in all age groups. These results suggest that specific care should be given to patients with intermittent claudication based on the age related causes of death. PMID- 11194285 TI - Diagnostic significance of the morphological change in the atrial electrogram during Para-Hisian pacing. AB - Para-Hisian pacing (PHP), a pacing method to differentiate between conduction occurring over an accessory pathway (AP) from that over the atrioventricular node (AVN), is assessed essentially by comparing the timing in the atrial electrogams. Morphological change in the atrial electrograms is often observed during PHP, but its significance has not been investigated. Prior to the catheter ablation procedure, PHP was performed in 52 patients with an AP and in 36 patients with AV nodal reentrant tachycardia (AVNRT). The morphological change in the atrial electrograms, which was retrospectively assessed between the His bundle and proximal right bundle branch (HB-RB) captured and non-captured beats, was identified in 15 of 52 patients with an AP and in 26 of 36 patients with AVNRT. The atrial electrogram in the 6 of these 15 AP patients changed its morphology without overlapping the ventricular electrogram. All 6 AP patients exhibited a PHP pattern with the presence of 2 retrograde conduction routes, an AP and the AVN. In the patients demonstrating no morphological change in the atrial electrogram, 33 of 37 AP patients and all 10 AVNRT patients had only one retrograde conduction route. Morphological change in the atrial electrogram without overlapping the ventricular electrogram seems to have diagnostic significance indicating the presence of both AP and AVN conduction. PMID- 11194286 TI - Clinical surveillance of a thin bipolar pacing lead. AB - A total number of 415 co-radial, bipolar pacing leads (189 atrial leads; 226 ventricular leads) were implanted in 228 patients between November 1994 and July 1999. Mean pacing thresholds at the implantation were normal at 0.6 V in the atrium and at 0.4 V in the ventricle with a pulse duration of 0.4-0.5 ms. Lead impedance was relatively low (337-447 ohms for atrial leads; 369-459 ohms for ventricular leads) at the implantation and during the follow-up periods. No definite failure in lead materials was observed in either atrial or ventricular leads (mean follow-up of 19.7 and 19.2 months, respectively: up to 52.9 months for both leads). Predicted clinical surveillance up to 10 years calculated statistically showed that the upper 95% confidence limit was a constant of 100%. The lower 95% confidence limits at 5, 7, and 10 years were estimated to be 98.0%, 97.2%, and 96.0%, respectively. From the present study, the ThinLine lead is reliable for both sensing and pacing thresholds, and has excellent predicted lead longevity. Nevertheless, further observation is required regarding cost performance, such as early replacement of the pacemaker generator, because of the lower pacing lead impedance. PMID- 11194287 TI - Detecting viable hibernating myocardium in chronic coronary artery disease--a comparison of resting 201Tl single photon emission computed tomography (SPECT), 99mTc-methoxy-isobutyl isonitrile SPECT after nitrate administration, and 201Tl SPECT after 201Tl-glucose-insulin infusion. AB - To identify and quantify the amount of viable hibernating myocardium in patients with chronic coronary artery disease, resting 201Tl single photon emission computed tomography (SPECT) was compared with 99mTc-methoxy-isobutyl isonitrile (MIBI) SPECT after nitrate infusion (nitrate-99mTc-MIBI) and 201Tl SPECT after 201Tl with glucose-insulin-potassium infusion (201Tl-GIK) in 25 patients. Twenty one patients also underwent completely left ventriculography beforehand and 5+/-4 months afterwards. SPECT images were divided into 9 segments and scored visually from 0 (normal uptake) to 3 (absent). The defect score was calculated as the summation of the total scores (TDS) in each patient. The TDS of nitrate-99mTc MIBI images (6.3+/-4.3) and 201Tl-GIK images (5.8+/-4.2) were significantly lower than the 7.4+/-4.3 of resting 201Tl images (p<0.01). Based on the improvement of wall motion after coronary revascularization, the sensitivity of 201Tl-GIK imaging (85%) was significantly higher (p<0.05), and that of nitrate-99mTc-MIBI imaging (79%) also tended to be higher (p=0.08), than that of 201Tl imaging (62%) in detecting viable myocardium. The specificity of the 3 methods was almost the same. The nitrate-99mTc-MIBI and 201Tl-GIK methods were more useful than the resting 201Tl method for evaluating viable hibernating myocardium. Furthermore, the 201Tl-GIK method may provide a more accurate estimate of the amount of viable myocardium than the nitrate-99mTc-MIBI method. PMID- 11194288 TI - Influence of age (body size) on the Fontan circulation--analysis by a theoretical model. AB - Among the original selection criteria for the Fontan operation, the recommended age at the time of surgery has been 4 years or older, but recent clinical data have indicated the feasibility of this procedure in younger patients. Because age may influence the properties of the systemic vascular bed, changes in systemic vascular resistance (Rs) and systemic vascular compliance (Cs) associated with physical development were quantified in 86 pediatric patients without known abnormalities of the systemic circulation, and the effects of age (body size) on Fontan circulation were then analyzed using an analytical model of the cardiovascular system. As the body surface area (BSA) of the patient decreased, Cs also decreased significantly (r=0.81, p<0.001). Based upon this relationship between BSA and Cs, the analytical model showed that the impedance (ventricular afterload) of the Fontan circulation significantly increased as Cs decreased with the decrease in BSA. Moreover, the increase in impedance in response to changes in heart rate or Rs was inversely proportional to the BSA. However, these findings were significant only when the BSA was below 0.3 m2. Small BSA, or a lower age, has minimal effects on the Fontan circulation until it comes close to the infant value, and thus the Fontan procedure may be feasible much earlier than formerly recommended when the hemodynamics are otherwise acceptable. PMID- 11194289 TI - Diagnostic usefulness of the post-exercise systolic blood pressure response for the detection of coronary artery disease in patients with diabetes mellitus. AB - Patients with diabetes mellitus (DM) often have a positive result on exercise testing despite a normal coronary arteriogram, which indicates that exercise induced ST depression is not always an accurate indicator of the presence of coronary artery disease (CAD) in such patients. The present study evaluated the usefulness of the post-exercise systolic blood pressure (SBP) response for the detection of CAD in 47 consecutive patients with DM. Significant stenotic lesions were detected by angiography in 25 patients; 18 of these had true positive (TP) exercise testing results, and 7 had false negative (FN) results. No significant stenotic lesions were detected in the remaining 22 patients and of these 10 had true negative (TN) exercise testing results, and 12 had false positive (FP) results. The SBP ratio (SBP after 3 min of recovery divided by the SBP at peak exercise) was significantly higher in patients with coronary stenoses than in those without. Analysis of the relative cumulative frequency revealed that a SBP ratio greater than 0.87 was associated with significant stenoses. The sensitivity, specificity, and accuracy of ST change combined with a SBP ratio greater than 0.87 for detecting stenoses in patients with DM were 68%, 82%, and 74%, respectively. These results suggest that calculating the SBP ratio, in combination with monitoring for ST depression, improves the accuracy of treadmill exercise testing for the detection of CAD in patients with DM. PMID- 11194290 TI - Clinical characteristics and prognosis of hospitalized patients with congestive heart failure--a study in Fukuoka, Japan. AB - The clinical characteristics and prognosis of patients with congestive heart failure (CHF) have been described by a number of previous studies, but very little information is available on this issue in Japan. This study aimed to delineate the clinical characteristics and prognosis of Japanese patients hospitalized with CHF. Medical records were reviewed for 230 consecutive patients at 5 teaching hospitals in Fukuoka, Japan from January to December 1997 and the survival and hospital readmission were followed through December 1999 (mean follow-up, 2.4 years). The study population had a high mean age, contained a larger population of women especially in the older ages, and had a higher incidence of overt HF (48%) despite a relatively normal ejection fraction on echocardiography. Major causes of CHF were ischemic, valvular, and hypertensive heart diseases. The 1-year mortality rate was as low as 8.3% whereas rates of hospital readmission because of an exacerbation of CHF were as high as 40% during the follow-up period. Patients hospitalized with CHF in routine clinical practice in Japan have characteristics that differ from those in the population included in community-based studies or large clinical trials. PMID- 11194291 TI - Usefulness of transesophageal echocardiographic monitoring in transluminal endovascular stent-graft repair for thoracic aortic aneurysm. AB - The endovascular stent-graft has been devised for the treatment of thoracic aortic aneurysm (TAA) to reduce complications associated with conventional surgical repair. The present study assessed the usefulness of transesophageal echocardiography (TEE) for intra- and post-operative examinations in patients treated with transluminal endovascular stent-graft repair for TAA. Nine patients with TAA and 2 with chronic type B aortic dissection were studied. Immediately after stent-graft deployment, perigraft leakage was evaluated with both intraoperative TEE and aortography. In 9 of 11 patients, TEE and aortography immediately after stent-graft deployment revealed the same perigraft leakage results. TEE might therefore be useful for evaluating perigraft leakage and thrombus formation after stent-graft repair for TAA and could be an alternative to aortography, especially for patients with renal dysfunction who have the possibility of contrast agent-induced complications. PMID- 11194292 TI - Brain natriuretic peptide predicts chronic atrial fibrillation after ventricular pacing in patients with sick sinus syndrome. AB - Chronic atrial fibrillation (AF) is one of the main complications of sick sinus syndrome (SSS). As previously reported, plasma brain natriuretic peptide (BNP), reflects hemodynamic changes in different pacing modes, as does plasma atrial natriuretic peptide (ANP), so the present study investigated whether plasma BNP or ANP can predict chronic AF after single-chamber ventricular (VVI) pacemaker implantation in patients with SSS. Plasma ANP and BNP levels were measured before and 1-3 months after implantation in 99 SSS patients. Long-term follow-up was conducted with chronic AF as an endpoint. Chronic AF occurred in 19 patients during a mean follow-up of 5.1 years. Plasma ANP and BNP were significantly higher in the patients who developed chronic AF after implantation than in those who did not, despite similar ANP and BNP levels between the 2 groups before implantation. Post-implant high BNP and a history of paroxysmal AF were independent predictors of chronic AF by a multivariate Cox proportional hazards analysis. Plasma BNP can predict the development of chronic AF after VVI pacemaker implantation in patients with SSS because increased levels may reflect latent hemodynamic abnormalities, which may contribute to the development of AF after VVI pacemaker implantation. PMID- 11194293 TI - Adenosine-induced coronary flow reserve in Watanabe heritable hyperlipidemic rabbits. AB - The Watanabe heritable hyperlipidemic (WHHL) rabbit develops coronary atherosclerosis and hypercholesterolemia because of a genetic deficiency of low density lipoprotein receptors and is therefore a good animal model for studying the relationships of coronary atherosclerosis, hypercholesterolemia and coronary flow reserve. The aim of the present study was to assess myocardial perfusion at baseline and during adenosine infusion (0.2 mg x kg(-1) x min(-1)) in 8 WHHL rabbits (13.8+/-0.5 months) with 13N-ammonia, small-animal positron emission tomography (PET) and colored microspheres. Results were compared with those from 6 age-matched Japanese white rabbits. Plaque distribution was also examined in the extramural coronary arteries. All 8 WHHL rabbits had coronary plaques, with 6 showing multiple plaques. Mean global myocardial blood flow (ml x min(-1) x g( 1)) did not differ significantly between control and WHHL groups both at baseline (3.67+/-0.72 vs 4.26+/-1.12 ml x min(-1) x g(-1), p=NS) and with adenosine (7.92+/-2.00 vs 9.27+/-2.91 ml x min(-1) x g(-1), p=NS), nor did coronary flow reserve (2.16+/-0.37 vs 2.18+/-0.41, p=NS). None showed evidence of regional perfusion abnormalities by visual and semiquantitative analyses of PET images. It was concluded that WHHL rabbits preserve adenosine-induced coronary flow reserve despite coronary atherosclerosis and hypercholesterolemia, suggesting that a compensatory mechanism develops in this animal model. PMID- 11194294 TI - Significance of pericardial cytokines in giant cell myocarditis in rats- pathological comparison to viral myocarditis in mice. AB - To investigate the precise disease progression in myocarditis, Lewis rats were injected with porcine cardiac myosin, and C3H/He mice were inoculated with coxsackievirus B3. Both were killed serially, and the hearts were stained with hematoxylin-eosin to compare their pathological characteristics. In viral myocarditis, viral replication in the myocardium resulted in myocardial necrosis with inflammation, and the lesions were distributed transmurally, as previously reported. On the other hand, in giant cell myocarditis, inflammatory lesions appeared at first around the capillaries in the epicardium, and thereafter spread transmurally. Pericardial effusion was noticed in all the rats with myocarditis in the fulminant stage. Levels of interleukin (IL) -1beta and IL-6 in the pericardial effusion were elevated compared with the serum cytokines at the peak of inflammation. However, interferon-gamma in both the pericardial effusion and serum was not elevated. The cause of the myocardial lesions that developed in rats with giant cell myocarditis may be some active inflammatory process via the pericardial effusion. PMID- 11194295 TI - Primary cardiac malignant fibrous histiocytoma in the right ventricular infundibulum treated with a cavo-pulmonary shunt and coronary embolization. AB - A 51-year-old woman presented with progressive right ventricular infundibular wall thickening and outflow obstruction. She had had an aorto-coronary bypass for left main coronary artery disease 1 year after radiation therapy for left mammary cancer. Enhanced computed tomography showed a mass in the right ventricular free wall with no connection to the mediastinum; the tumor extended into the main pulmonary artery, but there was no other evidence of a primary or metastatic tumor. A biopsy specimen was obtained and based on the microscopic and immuno histochemical findings (vimentin and Kp-1 positive) the diagnosis was primary cardiac malignant fibrous histiocytoma, which is very rare. A cavo-pulmonary artery connection lessened her symptoms, but embolization of the coronary artery to try and to reduce the mass had minimal effect. Four months after the tumor was diagnosed she died of extended pulmonary artery obstruction. PMID- 11194296 TI - Isolated coronary ostial stenosis associated with coronary vasospasm. AB - A 50-year-old woman was brought to the emergency room in a preshock condition. An emergency coronary angiogram revealed 90% ostial stenosis of the left coronary artery with delayed distal filling. After intracoronary nitrate, the degree of stenosis was reduced to 75%; no other coronary lesions were evident. The patient was found to have hyperthyroidism and she became euthyroid after a 2-month regimen of methimazole. A follow-up coronary angiogram showed that the left coronary artery had 50% ostial stenosis without delayed distal filling. At the same time, an aortogram showed complete occlusion of the right subclavian artery in its proximal site, a slight dilatation of the truncus brachiocephalic artery, and a diffuse wall irregularity of the abdominal aorta, suggestive of Takayasu's arteritis. PMID- 11194297 TI - Isolated left coronary ostial stenosis as a result of fibromuscular dysplasia in a young man. AB - A 28-year-old man was admitted to hospital for investigation of a 2-week history of angina occurring on exertion. Coronary angiography showed an isolated left coronary ostial stenosis and left main trunk plasty was performed 2 weeks later. The pathological diagnosis of the left coronary ostial stenosis was fibromuscular dysplasia, which makes this a rare case. PMID- 11194298 TI - Infective endocarditis with extensive calcified granulation of the mitral annulus and valve--a case report. AB - Mitral annular calcification, a degenerative process usually seen in the elderly or in chronic renal failure, is rarely seen in an extensive form. A 69-year-old man with no history of renal failure, rheumatic fever, or heart disease had mitral valve vegetation and regurgitation, together with extensive mitral annuls and valve calcification, which may or may not have been secondary to the infective endocarditis. PMID- 11194299 TI - Developments in Medicaid managed care. PMID- 11194300 TI - Staying the course: pursuing value in the Medicaid managed care era and beyond. PMID- 11194301 TI - Monitoring quality in Medicaid managed care: accomplishments and challenges at the year 2000. AB - This paper reviews the major developments during the late 1990s in quality monitoring for Medicaid managed care and offers an assessment of major challenges faced at the year 2000. We highlight the dramatic increase in activities to ensure and improve quality in Medicaid managed care. Prior to these developments, little was known about the actual level of quality of care. Thus, a major accomplishment of the late 1990s is that we now know more about quality, through some key indicators, and that states and plans have implemented activities and structures designed to improve quality. Despite this achievement, there is still a critical gap in our understanding about which activities and structures effectively improve the health of beneficiaries. There are also three operational challenges. First, as state quality assurance and improvement systems become increasingly comprehensive, states are challenged to keep them well coordinated and well targeted to key issues. Second, the dynamics of both plan turnover and enrollment-including steep drops in Medicaid enrollment-present a challenge for measuring and improving quality. A third challenge is to ensure that quality assurance and improvement programs work for enrollees with special health care needs. Finally, devoting sufficient resources to quality monitoring and improvement is a challenge for both states and plans since managed care programs are expected to save money as well as improve quality. PMID- 11194302 TI - Commercial managed care plans leaving the Medicaid managed care program in New York State: impact on quality and access. AB - To develop sufficient managed care capacity to accomplish the goal of transitioning Medicaid recipients into managed care, state policymakers have relied on commercial health maintenance organizations to open their panels of providers to the Medicaid population. However, while commercial health maintenance organization involvement in Medicaid managed care was high initially, since 1996 New York State has had 14 commercial plans leave the New York State Medicaid Managed Care Program. It has been speculated that the exodus of these commercial plans would have a negative impact on Medicaid enrollees' access and quality of care. This paper attempts to evaluate the impact of this departure from the perspective of quality and access measures and plan audit performance. Univariate and multivariate analyses were performed to evaluation the effect of commercial managed care plans leaving the Medicaid program. The overall performance of plans that remained in the program was compared to that of the plans that chose to leave for the two time periods 1996-1997 and 1998-2000. Access to care, quality of care, and annual audit performance data were analyzed. The departure of commercial health plans from the New York State Medicaid Managed Care Program has not had a statistically significant negative effect on the quality of care provided to Medicaid recipients as evaluated by standardized performance measures. In addition, there were no instances when there was a negative impact of the exit of the commercial plans on access to care. Managed care plans that chose to remain in Medicaid passed the Quality Assurance Reporting Requirements audit at a significantly (P < .01) higher rate than plans that chose to leave. CONCLUSIONS: A program consisting of health plans voluntarily participating and committed to Medicaid managed care can provide Medicaid recipients with appropriate access to high-quality health care. The exodus of commercial health plans from New York's Medicaid Managed Care Program during the time periods studied did not result in a detectable adverse impact on the quality of care for enrollees. PMID- 11194303 TI - Problems with quality monitoring for Medicaid managed care: perceptions of institutional and private providers in New York City. AB - The study objective was to examine quality oversight efforts by Medicaid managed care organizations (MCOs) for children in a sample of ambulatory care institutions and private practices in New York City. This was a cross-sectional study of quality assurance priorities and strategies of MCOs and their impact date in institutions in New York City. Data were from structured interviews administered in 1997 to medical directors in the eight largest MCOs; and medical directors, heads of ambulatory pediatrics, and institutional pediatricians in a random sample of 15 institutions and 20 private office-based providers. Medical directors in MCOs reported that their main priority areas were the preventive care measures (e.g., immunization and lead screening) that they must report to the state. Knowledge of these MCO priority areas and monitoring activities was high for medical directors in the random sample, but decreased from these medical directors to heads of ambulatory pediatrics to institutional pediatricians, with the differences between the medical directors and institutional pediatricians significant (P < .05). However, 96% of the institutional pediatricians reported knowing their own institution's priorities and monitoring activities. In contrast, most private pediatricians reported they knew MCO priorities and monitoring activities (80%). Less than 33% of any group reported activities as "very effective" or felt any incentive to improve performance. There was a high level of overlap in provider networks, with institutions and private providers having children in many MCOs, and MCOs having children in many sites. Conclusions. The current model of quality oversight is producing reports for the state, but is not translating into effective strategies at the provider level. The need to work through the leadership in institutions to influence quality is highlighted. The level of overlap in provider networks suggests the need for collaboration among MCOs in quality monitoring. PMID- 11194304 TI - A "best practices" strategy to improve quality in Medicaid managed care plans. AB - Medicaid managed care is delivered through organizations operating in very heterogeneous environments that confront similar barriers to success. Because Medicaid managed care is implemented differently in each state, health plans have been isolated from each other and have not had an opportunity to learn how others may have surmounted commonly encountered barriers. After interviewing Medicaid health plan medical directors, we developed a learning collaborative model based on shared categories of problems they would need to address before they could implement a successful improvement strategy in an important clinical area, birth outcome improvement. Under the Best Clinical and Administrative Practices initiative, we have brought together 12 Medicaid health plans to work together on strategies and specific objectives for overcoming obstacles to improvement. Evaluations by participants have been positive, and they appear to be making a number of specific organizational changes based on learning from the collaboratives. We will be employing this organizational development model to a series of clinically and administratively important topics over the next few years. PMID- 11194305 TI - Managed care for the Medicaid disabled: effect on utilization and costs. AB - The objective of this study was to describe the effect on health care utilization and costs of a program of managed care for the Medicaid disabled. The study was designed as a pre/post enrollment cohort comparison and was carried out in three Ohio counties. The subjects were disabled Medicaid-insured patients who voluntarily enrolled in a managed care program for at least 6 months between July 1, 1995 and December 31, 1997, and who had (1) at least one Medicaid claim in the 24-months pre-enrollment period and (2) overall satisfactory postenrollment encounter-level data. Ohio Medicaid provided claims and reimbursements (costs) for the pre-enrollment period and encounter-level data for the postenrollment period. Postenrollment costs were estimated by applying category-specific average pre-enrollment costs to postenrollment utilization data. We measured the following per patient-month: (1) trends in category-specific utilization and costs for up to 24 months before and after enrollment, (2) differences in overall and category-specific costs 1 year before and after enrollment, and (3) changes in the distribution of services 1 year before and after enrollment. Utilization categories included inpatient care, outpatient hospital (including emergency department) care, physician services, prescription medications, durable medical equipment and supplies, and home health care. We found that satisfactory encounter data were available in two of three counties. Of 1,179 enrollees, 592 met all inclusion criteria. Before enrollment, utilization and costs were increasing significantly in four of six categories and were unchanging in two. Postenrollment, decreasing utilization was observed for three categories, one remained unchanged, and two were increasing, but from a lower "baseline." Except for physician services and home health care, there were lower utilization and estimated costs in all categories in the year after enrollment. Estimated inpatient and total costs declined by $155/patient-month (44.9%) and $210/patient month (37.1%), respectively. Findings were similar across sites. Inpatient care, outpatient hospital care, and prescription medications accounted for 97% of the reductions in estimated costs in the postenrollment period. Among patients voluntarily enrolled for at least 6 months, managed care for the Medicaid disabled was associated with striking decreases in health care utilization and estimated costs. The effect of managed care on these patients' satisfaction, access to specialized services, quality of care, and health outcomes are understood incompletely. PMID- 11194306 TI - Analysis of selection effects in New York City's Medicaid managed care population prior to mandatory enrollment. AB - It is becoming increasingly apparent that over the next several years the majority of Medicaid patients in many states will become enrolled in managed care plans, some voluntarily, but most as the result of mandatory initiatives. An important issue related to this development is the extent to which this movement to managed care is accompanied by serious selection effects, either across the board during the phase in or among individual plans or plan types with full-scale implementation. This paper examines selection effects in New York City between 1993 and 1997 during the voluntary enrollment period prior to implementation of mandatory enrollment pursuant to a Section 1115 waiver. No substantial selection bias was documented between patients entering managed care and those remaining in the fee-for-service system among the largest rate groups, although some selection effect was found among plans and plan types (with investor-owned plans enrolling patients with lower prior utilization and expenses). PMID- 11194307 TI - Oil and water? Lessons from Maryland's effort to protect safety net providers in moving to Medicaid managed care. AB - Studies have highlighted the tensions that can arise between Medicaid managed care organizations and safety net providers. This article seeks to identify what other states can learn from Maryland's effort to include protections for safety net providers in its Medicaid managed care program--HealthChoice. Under HealthChoice, traditional provider systems can sponsor managed care organizations, historical providers are assured of having a role, patients can self-refer and have open access to certain public health providers, and capitation rates are risk adjusted through the use of adjusted clinical groups and claims data. The article is based on a week-long site visit to Maryland in fall 1998 that was one part of a seven-state study. Maryland's experience suggests that states have much to gain in the way of "good" public policy by considering the impact of their Medicaid managed care programs on the safety net, but states should not underestimate the challenges involved in balancing the need to protect the safety net with the need to contain costs and minimize the administrative burden on providers. No amount of protection can compensate for a poorly designed or implemented program. As the health care environment continues to change, so may the need for and the types of protections change. It also may be most difficult to guarantee adequate protections to those who need it most- among relatively financially insecure providers that have a limited management infrastructure and that depend heavily on Medicaid and the state for funds to care for the uninsured. PMID- 11194308 TI - A managed care/public health partnership: opportunities in New York City's Medicaid program. PMID- 11194309 TI - Evolution of federal policy on access to health care 1965 to 1980. 1983. PMID- 11194310 TI - The prevalence of homelessness among injection drug users with and without HIV infection. AB - Cross-sectional investigations of homelessness have many potential biases. Data from 2,452 individuals enrolled in a longitudinal cohort study of Baltimore, Maryland, residents recruited in 1988-1989 with a history of injection drug use were analyzed to identify the extent and determinants of homelessness. Proportions having ever experienced homelessness were compared across subgroups of injection drug users (IDUs) who were human immunodeficiency virus (HIV) negative, HIV positive, and HIV seroconverting. Logistic regression identified independent predictors of homelessness. In the cohort, 1,144 (46.7%) participants experienced homelessness during the course of the study. There were differences in prevalence of homelessness by serostatus: 42.4% (n = 621) of participants who remained HIV negative were ever homeless, while 50.6% (n = 346) of HIV-infected individuals and 58.9% (n = 178) of those who seroconverted during the study were ever homeless (P < .001). Participants who consistently denied active injection drug use during follow-up were unlikely to experience homelessness (19%). Independent predictors of homelessness were male sex, HIV seroprevalence, and HIV seroconversion. Following participants over time captures more experiences of homelessness than cross-sectional studies and more accurately identifies risk characteristics. Our data suggest that homelessness is a significant problem among IDUs, especially those with HIV/AIDS. PMID- 11194311 TI - Social costs of untreated opioid dependence. AB - Using cost-of-illness methodology applied to a comprehensive survey of 114 daily opiate users not currently in or seeking treatment for their addiction, we estimated the 1996 social costs of untreated opioid dependence in Toronto (Ontario, Canada). The survey collected data on social and demographic characteristics, drug use history, physical and mental health status, the use of health care and substance treatment services, drug use modality and sex-related risks of infectious diseases, sources of income, as well as criminality and involvement with the law enforcement system. The annual social cost generated by this sample, calculated at Canadian $5.086 million, is explained mostly by crime victimization (44.6%) and law enforcement (42.4%), followed by productivity losses (7.0%) and the utilization of health care (6.1%). Applying the $13,100 cost to the estimated 8,000 to 13,000 users and 2.456 million residents living in Toronto yields a range of social cost between $43 and $69 per capita. PMID- 11194312 TI - Reasons given for disclosure of maternal HIV status to children. AB - The purpose of this investigation was to ascertain the reasons given by mothers diagnosed with AIDS (acquired immunodeficiency syndrome) for disclosing or not disclosing their HIV (human immunodeficiency virus) status to their children, a dilemma faced by most HIV-infected parents and those who counsel them. We interviewed 29 mothers residing in one of two New York City facilities that provide housing and medical treatment for adults with AIDS. The majority of these mothers do not live with their children, but all had recent face-to-face contact with them. The two reasons most frequently considered important for disclosing to children were that disclosure was the "right thing to do" and the need to make arrangements for children's future in case of maternal death or incapacity. The reason most frequently considered important for not disclosing was maternal concern about discussing death and dying with children. These findings have significant implications for counseling of HIV-positive parents. PMID- 11194313 TI - Maternal mortality in New York City: excess mortality of black women. AB - To assess maternal mortality in New York City, birth certificates and mortality records for New York City from 1988 through 1994 were linked and examined. During these 7 years, maternal mortality in New York City (defined by the International Classification of Diseases, 9th edition [ICD-9], as 630-676) per 100,000 live births significantly exceeded that of the country as a whole (20.2 vs. 8.2, respectively). Within New York City, an even greater variation of maternal mortality by race/ethnicity was noted, with the mortality ratio of whites, blacks, and Hispanics being 7.1, 39.5, and 14.4 per 100,000 live births, respectively. Socioeconomic characteristics such as educational attainment, marital status, and income influenced maternal mortality more in non-blacks than blacks. Analyses of cause-specific mortality revealed that, overall, ectopic pregnancy, embolism, and hypertension were the leading causes of death. However, the major factors explaining the excess maternal mortality among blacks were hypertension (mortality ratio of blacks to whites 5.57, 95% confidence interval 2.30-13.39), ectopic pregnancy (4.78, 95% confidence interval 2.40-9.51), and abortion (4.58, 95% confidence interval 1.72-12.22). These findings confirm a persisting gap in maternal death between black and white women. Indeed, if all New Yorkers who became pregnant enjoyed the survival of the city's non-Hispanic white residents, the difference in maternal mortality between the city and the nation would be eliminated. PMID- 11194314 TI - The prevalence of asthma in children of elementary school age in western New York. AB - To determine the prevalence of caregiver-reported asthma in children 4 to 13 years old in metropolitan western New York State, surveys were conducted during 1997-1999 in the Buffalo, Niagara Falls, Iroquois, and Gowanda school systems. Questionnaires (3,889) were sent to the homes of elementary school children in nine schools in western New York. The caregivers were asked to complete a 13-item questionnaire for the child. Of the questionnaires, 60.5% (2,353/3,889) were completed. Of all children, 18% had physician-diagnosed asthma. Of children diagnosed with asthma, 86% were taking medication. Symptoms were consistent with suspected undiagnosed asthma for 13% of the children. Buffalo had the highest rate of diagnosed asthma (20%) for the age group. Gowanda had a prevalence of 18%, Iroquois 16%, and Niagara Falls 15%. Variations were observed in asthma prevalence rates among different racial/ethnic groups. In general, boys had a significantly (P = .001) increased odds of being asthmatic compared with girls. Overall, African-Americans and Hispanic/Latino children had significantly (P = .012 and P = .005, respectively) higher asthma prevalence rates, two to five times those of their Caucasian peers. In Gowanda, the prevalence of diagnosed asthma among Native American children was 23%, compared to 15% among Caucasian children. Of diagnosed Native American children, 71% were female. In Gowanda, a significant association (P = .007) of asthma among children in split-grade classes was observed compared to nonsplit grades. Of Native American children in split grades, 60% were diagnosed asthmatics. These observations reveal a high prevalence of asthma in the age group of 4 to 13 year olds in western New York. Local variations in potential triggers of asthma need to be considered when advising asthmatics. The results suggest that some grades have a disproportionate amount of children with asthma. The implications of asthma for children's early education need to be examined further. PMID- 11194315 TI - Expanded syringe access demonstration program in New York State: an intervention to prevent HIV/AIDS transmission. PMID- 11194316 TI - New York State pharmacists' attitudes toward needle and syringe sales to injection drug users before implementation of syringe deregulation. AB - In May 2000, New York State passed legislation permitting the sale, purchase, and possession of up to 10 needles and syringes without a prescription. The law is intended to reduce the transmission of human immunodeficiency virus (HIV) and hepatitis among injection drug users (IDUs), their sexual partners, and their children. To obtain baseline information about the attitudes and likely practices of New York State pharmacists, we distributed a self-administered questionnaire to attendees of the state pharmacy association meeting in June 2000. Of 48 usable responses, 19% were from New York City and the rest from New York State. Of the 48, 42% were unaware of the new law before the day of the survey, and 60% were somewhat or very willing to sell needles and syringes to an IDU. Of those who were not willing to sell to an IDU, 82% cited familiarity of the customer as a very important consideration in their decision making. Those who were not willing to sell to an IDU were more concerned about the detrimental impact of syringe sales on the community, were less likely to be aware of the new law, and were more likely to be concerned about legal liability for syringe sales. Over 80% of all pharmacists believed that syringe sales to IDUs are an important preventive health measure. The majority also favored learning more about the law. Compared to other state surveys of pharmacists, these preliminary data show a similar level of interest in becoming involved with syringe availability programs. PMID- 11194317 TI - New York City pharmacists' attitudes toward sale of needles/syringes to injection drug users before implementation of law expanding syringe access. AB - In May 2000, New York State passed legislation permitting the sale, purchase, and possession of up to 10 needles and syringes (hereafter "syringes") without a prescription, intended to reduce blood-borne pathogen transmission among injection drug users (IDUs). To obtain baseline data on pharmacists' attitudes and practices related to human immunodeficiency virus (HIV) prevention and IDUs, a telephone survey was administered to 130 pharmacists systematically selected in New York City. Less than half of pharmacists were aware of the new law; 49.6% were willing to or supported providing nonprescription sales of syringes to IDUs. Pharmacists in support tended to be less likely to consider customer appearance "very important." Managing and supervising pharmacists were more likely than staff pharmacists to support syringe sales to IDUs. Managing and supervising pharmacists who stocked packs of 10 syringes and personal sharps disposal containers, pharmacists who supported syringe exchange in the pharmacy, and pharmacists who were willing to sell syringes to diabetics without a prescription were more likely to support syringe sales to IDUs. Syringe disposal was a prominent concern among all pharmacists. Those not in support of syringe sales to IDUs tended to be more likely to believe the practice would increase drug use. These data suggest the need for initiatives to address concerns about syringe disposal and tailored continuing education classes for pharmacists on HIV and viral hepatitis prevention among IDUs. PMID- 11194318 TI - [Away from deficit orientation--emphasis on individual quality of life]. PMID- 11194319 TI - [Hygiene on the way to the future]. PMID- 11194320 TI - [Nosocomial infections are preventable]. PMID- 11194321 TI - [Washing the patient--"do you think of body care?"]. PMID- 11194322 TI - [Administration of nose drops: the best position is head down, legs up]. PMID- 11194323 TI - [Working together as a team to reach a goal]. PMID- 11194324 TI - [Introduction to the DGR system. I. The count-down runs relentlessly]. PMID- 11194325 TI - [When the DRG come to Germany in the year 2003: the transition in the delivery of health care will gain in importance]. PMID- 11194326 TI - [Regulations regarding costs of the nursing profession should be resumed]. PMID- 11194327 TI - [Tasks of nursing experts have many sides]. PMID- 11194328 TI - [Biographers need extensive knowledge about generations]. PMID- 11194329 TI - [The human body and its nursing care]. PMID- 11194330 TI - [Decubitus ulcer is always preventable]. PMID- 11194331 TI - [Does nursing need its own ethics?]. AB - In contrast to a medicine and medical ethics dominated by the physician, nurses claim more professional autonomy, domains of independent responsibility and recognition of their own moral judgment and ethical reflection. In my article I endorse these claims, but I object to the widespread opinion that their fulfillment requires a nursing ethics of its own, in the sense of a specific moral theory for nursing. Such a "special ethics" would be counterproductive to the concerns of nurses, and just as mistaken as a special medical or physicians ethics. Instead, a critique of medicine on the basis of a general ethics is required both for nurses and physicians. Part I presents arguments against mistaken conceptions of a special nursing ethics. Part II outlines elements of a general ethics for medicine and nursing. Part III explains my understanding of an ethical critique of medicine, which is founded upon the distinction of three conceptual dimensions of medicine: as science, institution and practice. This critique focuses the ethical attention on the life situation of the patient. Consequences for argumentative support and political fulfillment of the nurses' claims mentioned will thereby become evident. PMID- 11194332 TI - [Intuition as implicite knowledge]. AB - The article relates the terms intuition, tacit knowledge and experience and describes their meaning for nursing. An empirical study with 16 experienced nurses is presented whereby the nurses had to deal with a simulated critical nursing situation. Basing on their actions a method for explication of action guiding tacit knowledge was developed so that a closer scrutinizing of this type of knowledge became possible. Results underline the assumption of many practitioners that intuition as a resource in nursing activities is not to underestimate. At the same time a warning is given: Intuition and tacit knowledge is not always and at all times to evaluate positively. Finally, this differentiated point of view is discussed regarding consequences for nursing practice. PMID- 11194333 TI - [Study on quality assurance in the prevention and therapy of decubitus ulcer by measuring the overlay pressure with test subjects on different prophylaxis systems]. AB - The aim of this study on quality assurance in prevention and treatment of bedsores was to analyse the current state of treatment of pressure sores at the University Hospital in Marburg. Measurements of pressure exerted on the skin were taken of six soft storage systems and five alternating pressure systems. In addition, the study aimed to find out whether the applied method of pneumatic pressure measurement could be used with patients in every day nursing and whether reliable and valid data could be generated from patients who have already developed bedsores. In order to answer these questions measurements were taken on 23/19 patients, including patients in lateral position, placing measuring instruments between the mattress/bed system and the body. The soft storage systems results prove a significant pressure reduction at all measuring points (p < 0.05), at the os coccygis even a highly significant pressure reduction (p < 0.01). The alternating pressure systems results show that the average maximum pressure over 12 min lies between 56.39 mmHg and 38.94 mmHg with differing amplitudes (75.47 mmHg-5 mmHg) and alternating frequency (1.5 min-10 min). PMID- 11194334 TI - [The influence of nursing measures on incision pain and the use of opioids in the postoperative period]. AB - This experimental study was designed to investigate the influence of a cognitive behavioural technique on elective abdominal-surgical and orthopaedic patients at seven different time points within the first 72 postoperative hours. It examines the effect of deep breathing relaxation on the anxiety, distress, and incisional pain levels of postoperative surgical patients. The results show that the cognitive behavioural technique positively affects postoperative perception of pain, energy level, relaxed state and strain within the experimental group. The technique did not influence the patients' postoperative state-anxiety and agitation. Postoperatively, patients from the experimental group in both surgical areas used more opioids than patients from the control group. Preoperatively assessed personality factors did not differ between both groups. Overall the findings suggest that the implementation of a deep breathing relaxation technique positively influences the postoperative course of elective abdominal-surgical and orthopaedic patients. PMID- 11194335 TI - [Families living with HIV and Aids--review of the literature]. AB - This article presents the current state of the art regarding the concept of families living with HIV and Aids. The literature reflects a comprehensive view including families of origin, families of choice and partnerships. It is evident that family networks of homosexual men are most systematically described in the literature; to a lesser extent families with hemophilia and i.v. drug users and even fewer studies are found regarding families with a heterosexual transmission background and especially female family caregivers. This paper also focuses on the wide range of support offered by these family systems. The acute and mostly terminal infectious disease Aids, as observed in the 80 Dies, has now become a predominantly chronic-progressive illness. Since the mid 90 Dies, the new antiretroviral therapies have further decreased morbidity and mortality, leading to less personal care, high-tech nursing requirements and household support. This development places families in a position of providing more emotional and advocatory support and companionship over a considerably longer time span. The discussion identifies strengths and weaknesses of the current literature in order to define deficits in the Anglo-American as well as in the German speaking area. From a nursing science point of view, the characteristics of HIV/Aids care must be further acknowledged, described and systematically studied, and results must be made accessible. This is important because the knowledge acquired by studying families affected by HIV and Aids is of interest for other family systems dealing with chronically ill family members. Finally, research recommendations are listed regarding family-oriented care and future study designs. PMID- 11194336 TI - [Pain management and nursing care--results of a review of the literature]. AB - Especially for patients with chronic conditions, the ability to cope with the experience of illness in their daily lives is essential for the quality of life. An analysis of the international literature, of German nursing textbooks and journals was carried out to determine the dissemination of the state of the art of pain management. International research findings indicate a wide gap between the state of the art and pain management practice. Multidisciplinary role model programs where nurses play a major role as change agents have proved to be an effective strategy to change the institutional practice of pain management. In Germany, pain therapy as a medical discipline as well as academic courses in nursing were only institutionalized in the last decade. As a consequence pain research and therapy remained the domain of medicine and psychology up to now. Enhancing knowledge and educative skills of nurses will not only promote the quality of care. It is a key concept of professionalization in nursing. PMID- 11194338 TI - [Endangered by narcotic gases in the operating room?]. PMID- 11194337 TI - [Dr. Gustav Feldmann (1872-1947)--promoter of Jewish nursing in Germany]. AB - The origins of Jewish nursing in Germany date back to the last part of the 19th Century. In the wake of national socialism tyranny (NS-Zeit), the existence of Jewish nursing was completely destroyed. Regarding establishment and solicitous development for Jewish women, owing to a Jewish doctor living in Stuttgart Dr. Gustav Feldmann (1872-1947) whose contribution to developing new profession in the first quarter of the 20th century was not without merit. Up to now, he was hardly recognized by medical history and historical research. The following contribution serves to get a better view of his life and activities; most importantly to introduce his published work to a wide readership. PMID- 11194339 TI - [Operating room nursing--continuing education or technical assistant?]. PMID- 11194340 TI - [Diagnosis-related groups--a subject for nursing, or not?]. PMID- 11194341 TI - [Mutual supervision by colleagues. A method of quality assurance in patient care]. PMID- 11194342 TI - [Pain in old age]. PMID- 11194343 TI - [Animals at the psychiatric hospital]. PMID- 11194344 TI - [Basal stimulation in severe burns. Limits to be observed--resources used]. PMID- 11194345 TI - [Minor amputation on the foot--ambulatory surgery under conduction anesthesia]. PMID- 11194346 TI - ["Keyhole" surgery, even on the spine]. PMID- 11194347 TI - [Managing suicidal patients in hospital]. PMID- 11194348 TI - [Chronic wounds]. PMID- 11194349 TI - [Is it logical or not? Understanding the logic of demented patients]. PMID- 11194350 TI - [What is new in the treatment of diabetes mellitus?]. PMID- 11194351 TI - [Understanding comes from observation. The DCM method (Dementia Care Mapping)]. PMID- 11194352 TI - [Tegaserod]. PMID- 11194353 TI - [Age-related macular degeneration (AMD)--a frequent cause of vision loss in the aged]. PMID- 11194354 TI - [Photodynamic therapy with Vsudyne (Verteporfin)--an innovative therapy of age related macular degeneration]. PMID- 11194355 TI - [Early Tamiflu therapy of influenza can reduce disease time by half]. PMID- 11194356 TI - In vivo resistance of coronally induced bacterial ingress by an experimental glass ionomer cement root canal sealer. AB - The resistance of an experimental sealer (KT-308) to bacterial ingress was assessed in six beagle dogs. In four mandibular premolars per dog, canals were prepared, filled with condensed gutta-percha and either KT-308 or Roth 801 cement (n = 24 roots), and the pulp chambers inoculated with plaque. Two additional premolars per dog were similarly root-filled, but not inoculated (n = 12 and 11, respectively). One incisor per dog was inoculated, but not root-filled (n = 6). Dogs were terminated after 6 months, and jaw blocks were retrieved and processed for light microscopic examination of the periapical tissues. Inflammation about the inoculated roots was significantly lower (p < 0.03) for KT-308 (17%) than Roth 801 cement (46%). Inflammation about the noninoculated roots did not differ significantly between KT-308 (8%) and Roth 801 cement (36%). This study demonstrated a better functional efficacy of KT-308 than of Roth 801 cement, and validated this in vivo model for assessment of root filling materials. PMID- 11194357 TI - Characterization of reactive oxygen species generated from the mixture of NaClO and H2O2 used as root canal irrigants. AB - Characterization of a mixed solution of sodium hypochlorite (NaClO) and hydrogen peroxide (H2O2), which have been used as root canal irrigants, was investigated using electron spin resonance spectroscopy combined with a spin-trapping technique. In the solution, two kinds of reactive oxygen species, the superoxide anion radical (O2-.) and the hydroxyl radical (.OH), were detected. The pH changes and dissolved oxygen values in the NaClO-H2O2 reaction mixture were investigated. The pH influenced the generation of O2-. and .OH, and O2 was generated from H2O2. It is suggested that root canal irrigation with NaClO and H2O2 induces biological effects, such as tissue irritation (from the chemical reactions of O2-. and .OH) and physical effects, such as O2 bubbling. PMID- 11194358 TI - Identification of G-protein coupled receptor subunits in normal human dental pulp. AB - To respond appropriately to their environment, dental pulp cells must integrate informational input from multiple ligands, such as neuropeptides, growth factors, and vasoactive amines. These ligands act through multiple intracellular signaling pathways. G-protein coupled receptor subunits play a major role in this process, providing a mechanism for coordinated regulation of both messengers and effectors. Increasing number of neuropeptides have been found in pulpal tissue. However, there is no data about molecular identification of G-protein subunits in human dental pulp. To identify the postreceptor mechanism involved in dental pulp cell signal transduction, we performed a Western blot analysis of different G protein subunits. Biopsy specimens of human dental pulp were prepared and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by analysis with appropriate antibodies. We detected G alpha q/alpha 11, short and long forms of G alpha s, beta common, Gio-3, and Gil-2 antigens with a molecular weight approximately 42 kDa, 42 and 45 kDa, 36 kDa, 40 kDa, and 40 kDa, respectively. These results indicate that human pulp cells possess the cellular machinery to respond to sensory neuropeptides when they are released from the peptidergic nerve fibers. On this basis, the relationships of postdevelopmental, age-dependent, and pathophysiological disorders of G-proteins subunits in dental pulp could be studied. PMID- 11194359 TI - Suppression of bacterial adherence by experimental root canal sealers. AB - To prevent reinfection after root canal treatment, root filling materials should be antimicrobial. This study assessed the antimicrobial efficacy of KT-308, a modified glass ionomer cement sealer, and three formulations of ZUT, a combination of KT-308 and three different concentrations of a silver-containing zeolite. Discs prepared from the test materials and paper controls were incubated in Brain Heart Infusion broth for 12 wk. At 2-wk intervals, 18 discs from each group were inoculated with Enterococcus faecalis and incubated for periods of 1 to 30 h. After further processing, a 200 microliters aliquot of the broth immersing each disc was plated on agar and assessed for bacterial growth. The remaining broth was measured for optical density. All ZUT discs demonstrated no bacterial growth after 15 h of interaction, in contrast to abundant growth with the KT-308 and paper discs. Thus ZUT effectively suppressed adherent E. faecalis after 15 h, irrespective of its concentration and age. PMID- 11194360 TI - Bleaching effect of sodium percarbonate on discolored pulpless teeth in vitro. AB - The purpose of this study was to evaluate the bleaching effect of sodium percarbonate on artificially stained pulpless teeth. Twenty extracted human mandibular premolars were stained by immersing them in human blood mixed with iron sulfide, and divided into three test groups and one control group. The following bleaching agents were used: sodium perborate mixed with 30% hydrogen peroxide (WB), sodium percarbonate mixed with distilled water (PW) or 30% hydrogen peroxide (PH). On days 5, 10, and 15, each pulp chamber was refilled with fresh bleaching paste. The L* (average lightness) of the midbuccal area of specimens was measured before and after staining, and on days 5, 10, 15, and 20 by colorimeter. The bleaching effect was evaluated by the lightness recovery rate (LRR) calculated from L*. WB showed the highest LRR among all groups, and PW and PH showed significantly higher LRR when compared with the control group. PW and PH were not significantly different. Results showed that sodium percarbonate had an obvious bleaching effect without hydrogen peroxide and indicated that it could be a safe intracoronal bleaching agent. PMID- 11194361 TI - Leakage of amalgam, composite, and Super-EBA, compared with a new retrofill material: bone cement. AB - An in vitro leakage study was conducted to compare the root-end sealing ability of amalgam with cavity varnish, composite with dentin bonding agent, and Super EBA with a new retrofill material: bone cement. Eighty single-rooted teeth were instrumented and obturated with gutta percha, resected and retroprepared. The teeth were then randomly divided into 4 groups of 20, with each group receiving one of the previously mentioned retrofill materials. The bone cement group was either etched or unetched. The teeth were immersed in silver nitrate and developer for leakage assessment. The teeth were grooved and split longitudinally to measure leakage. Statistical analysis showed that amalgam leaked significantly less than Super-EBA and unetched bone cement; composite leaked significantly less than Super-EBA. Amalgam was not statistically different from composite or etched bone cement. No significant difference between composite and both bone cements was noted, nor between both bone cements and Super-EBA. PMID- 11194362 TI - Radiovisiography in the detection of periapical lesions. AB - The periapical areas of 16 teeth from 6 human mandibular jaw specimens were randomly examined by 3 observers using conventional radiography with Kodak E speed film and radiovisiography (with variable contrast and with fixed contrast). Each periapical area was examined preoperatively and after #2, #4, #6, and #8 sized bur periapical lesions were created in the cortical bone. The three radiographic methods were compared by repeated-measures ANOVA of the accuracy scores for the 16 periapical lesions. Accuracy increased with size of lesion, but did not vary by method. Repeated-measures ANOVA of the accuracy scores of only the smallest and no lesion condition showed that conventional radiography and radiovisiography (variable contrast) have opposite strengths. Conventional radiography tended to be more accurate in the no lesion condition, whereas radiovisiography using variable contrast was somewhat more accurate in the smallest lesion condition. The accuracy of radiovisiography with fixed contrast was not significantly different from the other two methods. PMID- 11194363 TI - Three-dimensional reconstruction: a new method for the evaluation of apical microleakage. AB - The purpose of this study was the evaluation of a new method for studying apical microleakage by using a three-dimensional (3-D) reconstruction method. Fourteen human single-rooted mandibular teeth were used for this work. The canals were prepared with hand instruments by using the step-back technique. To supply a focus to the study of the method, the teeth were divided into two groups that were obturated using two different sealers. India ink was used for passive stain. Serial cross-sections 0.75 mm thick were taken from each specimen by using a special microtome. Each section was photographed under a stereoscopic microscope. Each photograph was digitized and processed to obtain a 3-D reconstruction of the external surface of the teeth, their corresponding prepared root canals, and their apical microleakage. Sample size and experimental methods were not designed to make valid groups; however, apical microleakage was observed in both groups ranging between 2.25 to 8.25 mm height. The 3-D reconstruction method has proved to be a useful tool in the study of apical microleakage. PMID- 11194364 TI - Interpretation of artificial and in vivo periapical bone lesions comparing conventional viewing versus a video conferencing system. AB - The purpose of this study was to compare the interpretation of conventional radiographs transmitted by a video teleconferencing system to conventional viewbox interpretation for both artificial and in vivo periapical bone lesions. A total of 30 radiographic images were used in this study: 20 radiographic images of artificial lesions and 10 radiographs from actual patients. Two endodontists evaluated the 30 images by giving a "yes" or "no" response when determining whether a periapical lesion was present on the radiograph. The study was conducted in two sessions, separated by a 6-wk interval to minimize evaluator recall. Results of the study revealed no statistical difference between the ability of the evaluator to identify periapical bone lesions using conventional radiographs on a viewbox and his ability to interpret the same images transmitted on a monitor screen. PMID- 11194365 TI - Comparison of nickel-titanium and stainless-steel spreader penetration and accessory cone fit in curved canals. AB - The purpose of this study was to compare nickel-titanium and stainless-steel spreader penetration in curved canals. Twenty prepared plastic blocks with a 30 degrees curvature were used for each part of the study. In part 1, the force required to insert each spreader to within 1 mm of working length in an empty canal was measured. In part 2, the force required to insert each spreader to within 3 mm of working length was measured in a canal containing a master cone. In part 3, the depth of penetration of each spreader with a master cone in place using a 1.5 kg force was measured. Additionally, in part 3, the depth of penetration of the first accessory cone was measured. The results from part 1 showed that a nickel-titanium spreader required significantly less force than a stainless-steel spreader (0.30 kg vs. 0.59 kg). In part 2, a nickel-titanium spreader required significantly less force than a stainless-steel spreader (1.56 kg vs. 2.42 kg). In part 3, a nickel-titanium spreader penetrated significantly deeper than a stainless-steel spreader (15.0 mm vs. 14.0 mm). There was no significant difference in the depth of penetration of the first accessory cone used after either spreader (0.8 mm vs. 0.7 mm). Therefore, the potential for vertical root fracture in curved canals during lateral condensation may be minimized by using nickel-titanium spreaders. PMID- 11194366 TI - A supernumerary tooth fused to the facial surface of a maxillary permanent central incisor: case report. AB - A case of a supernumerary tooth fused to the facial surface of a maxillary permanent central incisor is reported. Root canal therapy on the maxillary central incisor was performed due to pulpal communication between the supernumerary tooth and the maxillary central incisor after removing the supernumerary tooth structure. The communication was sealed with mineral trioxide aggregate. The difference between fusion and gemination is discussed. PMID- 11194367 TI - An accident with a Gates Glidden drill in endodontic practice. AB - An unusual accident in clinical endodontic practice is described. The Gates Glidden drill is currently being used for establishing straight-line access in endodontic practice (1). One potential hazard in using the Gates Glidden drill is that it can separate within the canal (2). This article reports an accident involving a Gates Glidden drill separating in the elbow of a dentist during endodontic practice and to discuss the safety of using a Gates Glidden drill. PMID- 11194368 TI - Zebra. XVIII. Part 2. Adenoid cystic carcinoma. PMID- 11194369 TI - Effects of irrigation on debris and smear layer on canal walls prepared by two rotary techniques: a scanning electron microscopic study. AB - Debris and smear layer were evaluated in canals prepared with either Lightspeed (LS) or ProFile (PF) rotary instruments. Irrigants used were tap water (group A) or alternating 5.25% NaOCl and 17% EDTA (group B). Apical stops were prepared to size 52.5 in the LS and to size 6 (approximately ISO size 36) in the PF techniques. The roots were split longitudinally and examined at apical, middle and coronal levels for debris and the smear layer using a 5-step scale. Using only water, mean debris scores were similar for LS and PF. In contrast, with EDTA/NaOCl, LS- and PF-prepared canals had similar debris scores at the apical and coronal levels, but there was a significant difference at the middle level. Mean smear layer scores were similar in LS- and PF-shaped canals when water was the sole irrigant. In contrast, with NaOCl and EDTA, mean smear layer scores were significantly different at the apical and middle levels, but not at the coronal level. Neither technique was superior in removing debris, but larger canal preparations obtained in this study with LS instruments enabled a more effective removal of the smear layer in the EDTA-NaOCl group. PMID- 11194370 TI - Effectiveness of ProFile .04 taper rotary instruments in endodontic retreatment. AB - This study investigated the retreatment effectiveness of .04 Taper nickel titanium rotary ProFiles. Thirty extracted single-rooted anterior teeth were instrumented and obturated with gutta-percha/Roth's Sealer using lateral condensation. They were distributed into three groups of 10 each. Retreatment for group A was done using Profile alone, group B using Profile and chloroform, and group C using hand files with chloroform. The teeth were then split longitudinally into halves. The remaining gutta-percha/sealer on the root canal wall in the cervical, middle, apical thirds, and the whole canals were visually scored with the aid of light microscopes. The results showed that the mean scores in groups A and B were generally lower (better) than group C. Mean scores of the apical thirds tended to be higher (worse) than the middle and the cervical thirds, except in group A. ProFile with or without chloroform seemed to be a viable alternative retreatment method. PMID- 11194371 TI - Three-rooted maxillary second premolar. AB - The possibility of three canals in maxillary second premolars is quite small; however, it must be taken into account in clinical and radiographic evaluations during endodontic treatment. Many times their presence is noticed only after canal treatment, due to continuing postoperative discomfort. This article describes a clinical case of three-canal maxillary second premolars that are endodontically treated. PMID- 11194372 TI - Endodontic considerations of the nasopalatine duct region. AB - Although rare, anomalies of the nasopalatine region have been reported in the literature mimicking pathoses of endodontic origin. The purpose of this article is to present a case of a patent nasopalatine duct that was originally diagnosed as a sinus tract and referred for endodontic therapy. A review of the anatomy of the nasopalatine region is also discussed. PMID- 11194373 TI - Comparison of digital dental X-ray systems with self-developing film and manual processing for endodontic file length determination. AB - Human skulls were sectioned into 15 sextants. Teeth were then removed and 45 canals were instrumented to their apical foramina. Endodontic files were glued in place at random distances from the apical foramina. Image geometry was maintained by a custom mounting jig. Images were captured with self-developing film, manually processed D-speed film, and a digital radiographic system (Dexis). Digital images were read on a conventional color monitor (cathode ray tube) and a laptop screen (active-matrix liquid crystal display). Fifteen dentists measured the distance from the file tip to the apical foramen of the tooth. Results showed that the measurement error was significantly less for the digital images than for the film-based images. It is likely that these statistical differences may not be of great clinical significance because the digital images could be measured in increments < 0.25 mm. PMID- 11194374 TI - Effect of rotational speed on the breakage of nickel-titanium rotary files. AB - Nickel-titanium 0.04-tapered rotary files were evaluated for breakage at different rotational speeds in semicircular bovine bone simulated root canals of identical size and radius for each file size group tested. The bovine bone canals had a radius of curvature of 5 mm and a canal width equivalent to the D1 diameter of the file plus 0.04 mm. Profile instrument #3, #4, and #5 were tested at 150, 250, and 350 rpm. A contra-angle electric handpiece was mounted on an Instron machine that was set to deliver a constant downward speed of 5 mm/min. The electric handpiece and Instron machine were activated until the files broke. The amount of file tip penetration into the semicircular bovine bone canal was measured in degrees with a protractor from a radiographic image taken of the file inside the bone model. Greater degrees of tip penetration indicated greater resistance to breakage. Statistical analysis was done and the results indicated that there was a significant difference for all file sizes in the extent of file tip penetration before breakage. In the rotation range between 150 and 350 rpm the greatest extent of penetration occurred at 150 rpm. This study concluded that 0.04 taper nickel-titanium rotary file breakage is less likely to occur if the files are rotated at lower speeds. PMID- 11194376 TI - Torsional properties of stainless-steel and nickel-titanium files after multiple autoclave sterilizations. AB - This study tested the hypothesis that multiple sterilizations of endodontic stainless-steel and nickel-titanium files will lead to a continuous decrease in the resistance of files to separation by torsion. One hundred stainless-steel and 100 nickel-titanium #30 K-type files were divided into 20 groups of 10 and sterilized in increments of 10 cycles, using a full cycle and a fast cycle autoclave. These files were tested by twisting each of them in a clockwise direction until fracture (torque g-cm). Samples of the fractured files were embedded in an epoxy resin and polished for Knoop hardness tests. In addition, the samples were chemically etched to reveal changes in microstructure. The findings of this study indicate that neither the number of sterilization cycles nor the type of autoclave sterilization used affects the torsional properties, hardness, and microstructure of stainless-steel and nickel-titanium files. PMID- 11194375 TI - Effects of ultrasonic root-end preparation on microcrack formation and leakage. AB - Root-end preparations made with conventional ultrasonic (CUS) tips, diamond coated ultrasonic (DUS) tips, and high-speed stainless-steel burs (HSB) were compared for the incidence of microcracks and dye leakage. One hundred twenty incisors were instrumented, obturated, and had 3 mm resected from their apices. Sixty teeth were used for microcrack evaluation before and after root-end preparation with CUS, DUS, or HSB. Three types of microcracks were observed: intracanal, extracanal, and communicating. Four of the five cracks observed after root resection (before root-end preparation) were of the extracanal or intracanal type. After root-end preparation, 19 of the 41 new microcracks that developed were the communicating type. There was no significant difference among CUS, DUS, or HSB for the number or type of cracks. Of the remaining 60 resected teeth, 25 were prepared with DUS, 25 with CUS, and 10 served as controls. All of the DUS and CUS teeth were filled with Super-EBA. Dye penetration was measured after immersion in Pelikan ink for 5 days. The dye penetration difference between DUS and CUS was not significant. PMID- 11194377 TI - Endothelial cell and stromal antigens in human periapical granulation tissue. AB - Periapical granulation tissue consists of vasculature of varying sizes and types, infiltrating cells, and other stromal elements. We examined the differential expression of endothelial and stroma antigens in this tissue to determine their tissue distribution in order to obtain hints on their functions. Some of the antigens examined were present only in the endothelial lining of vasculature, including high endothelial venules (e.g. CD31 and CD105), whereas others were more widely expressed by both vascular and stromal elements (e.g. CD29, CD63, CD44, and CD151). Immunohistochemical analysis using monoclonal antibodies specific to certain tissue compartments revealed the tissue architecture more precisely and the expression of certain antigens in the tissue suggested special roles for these antigens. Tissue distribution of CD63, CD143, CD147, and CD151 in periapical granulation tissue is first reported in the present study. PMID- 11194378 TI - Heat transfer to the periodontal ligament during root obturation procedures using an in vitro model. AB - It appears to be important to avoid thermal injury to the periodontal ligament when using heated guttapercha techniques such as "System B." An in vitro model was developed, consisting of an extracted human tooth rooted in an artificial periodontal ligament (PDL) and alveolar socket, which allowed us to measure the temperature transferred to the root surface. The teeth were instrumented and subsequently embedded in alginate to simulate the PDL. Medium gutta-percha points were fit, sealer was applied, and a fine Buchanan plugger was used for condensation. Temperature measurements were taken simultaneously at the apex and 5 mm from the apex during obturation with two fine gauge thermocouples connected to a digital thermometer. The average temperature increase was approximately 1 degree C at the apex and approximately 2 degrees C at the 5 mm mark. The resulting temperature increases appear to be lower than previously reported by other investigators (Hardie, 1986, 1987; Barkhordar et al., 1990; Weller et al., 1991; Lee et al., 1998), who did not allow for the heat disseminating effect of the PDL. PMID- 11194379 TI - Time course of the increase in trk A expression in trigeminal neurons after tooth injury. AB - Injury to tooth pulp often results in extensive sprouting of sensory nerve fibers at the site of wound repair due to local increases in nerve growth factor (NGF) concentration. NGF interacts with high-affinity binding sites, termed trk A receptors, located on the cell membranes of responsive neurons. If NGF induces wound repair and/or nociceptive responses in tooth pulp, then changes in expression of NGF receptors (trk A receptors) in response to dentin injury would be expected. To characterize the role of trk A receptors in mediating NGF-induced signals to sensory neurons, trigeminal ganglia from adult male rats were examined for changes in expression of trk A as a function of time after injury to maxillary molar dentin. In situ hybridization was performed with 35S-labeled riboprobes encoding the sense or antisense trk A sequences, and grain densities quantified over maxillary neurons. As early as 12 h after tooth injury, grain density counts increased by 71% above control level, indicating an increase in trk A receptor mRNA expression. Grain densities obtained from ganglia harvested at all time points through 168 h after injury remained elevated. At 336 h (14 days) after injury, trk A receptor expression had decreased such that grain density counts were not different from preinjury levels. Thus our results suggest that NGF may be mediating repair and pain responses by the sustained upregulation of its cell surface receptor, trk A, in neurons of the trigeminal ganglia. PMID- 11194380 TI - Penetration of the pulp chamber by bleaching agents in teeth restored with various restorative materials. AB - It is thought that externally applied bleaching agents may penetrate into the pulp chamber. This study was conducted to evaluate the diffusion of peroxide bleaching agents into the pulp chamber of teeth restored with various restorative materials. Sixty-five human extracted anterior maxillary teeth were separated into the 13 groups containing 5 teeth. Five teeth (control group) were not subjected to any cavity preparation and restoration. Standardized class V cavities were prepared in the other 60 teeth and restored using composite resin (Charisma), polyacid modified composite resin (Dyract), or resin-modified glass ionomer cement (Vitremer). All teeth were sectioned 3 mm apical to the cementoenamel junction to remove the intracoronal pulp tissue, and the pulp chamber was filled with acetate buffer to absorb and stabilize any peroxide that might penetrate. Vestibular crown surfaces of teeth in the experimental groups were subjected to four different bleaching agents for 30 min at 37 degrees C, whereas the teeth in the control groups were exposed only to distilled water. Then the acetate buffer solution in the pulp chamber of each tooth was removed, and the pulp chamber of each tooth was rinsed with 100 ml of distilled water twice. Leukocrystal violet and enzyme horseradish peroxidase were added to the mixture of the acetate buffer and rinse water. The optical density of the resulting blue solution was determined spectrophotometrically and converted into microgram equivalents of hydrogen peroxide. Higher hydrogen peroxide concentrations resulted in a higher pulpal peroxide penetration. The highest pulpal peroxide penetration was found in resin-modified glass ionomer cement groups, whereas composite resin groups showed the lowest pulpal peroxide penetration. PMID- 11194381 TI - A histopathological and immunohistochemical study of dental pulp and pulpal nerve fibers in rats after the cavity preparation using Er:YAG laser. AB - The purpose of this study was to investigate histopathological changes in the dental pulp after Er:YAG laser irradiation compared with those after high-speed drill preparation. For evaluation, repair of nerve fibers was observed using an immunohistochemical technique. There was no significant difference between the remaining dentin thickness in either cases. (Mann-Whitney U test). In the Er:YAG laser group a marked fibroblast proliferation and the formation of reparative dentin were observed relative to the high-speed drill group. The time course of the increase and decrease in calcitonin gene-related peptide-immunoreactive fibers in the high-speed drill group was similar to that of previous reports. In the Er:YAG laser group an increase in calcitonin gene-related peptide immunoreactive fibers was seen earlier than in the high-speed drill group, and 7 days after operation these fibers decreased to control level. The results suggested that the Er:YAG laser leads to pulpal repair earlier than the high speed drill. PMID- 11194382 TI - [Perioperative management with short-acting intravenous anesthetics]. AB - Total intravenous anaesthesia (TIVA) with short-acting drugs is a standard procedure for day case surgery and is increasingly used for neurosurgical, cardiac surgical and paediatric surgical operations. The combination of propofol with alfentanil or remifentanil is frequently applied due to its favourable pharmacological properties. Propofol is characterized by a large volume of distribution at steady state and a relatively long elimination half time (t1/2 beta). Because of a high metabolic clearance, the clinical effects of propofol decline rapidly even after prolonged intravenous drug infusion. In patients with increased age, obesity or liver or renal failure, decreased doses of propofol for induction of anaesthesia are recommended. The short-acting opioids alfentanil and remifentanil provide small volumes of distribution at steady state, a short blood brain equilibration time and decreased t1/2 beta. Remifentanil has unique pharmacological properties due to an ester binding and its elimination via extrahepatic hydrolysis by non-specific blood and tissue esterases. The context sensitive half time of remifentanil is significantly shorter than that of other opioids. Its analgetic potency is equal to fentanyl and 20 to 30 times higher than alfentanil. The advantages of total intravenous anaesthesia include fewer haemodynamic side-effects, a decreased incidence of postoperative nausea and vomiting and less neurohumoral stress response to surgery. Adequate pain therapy is mandatory after total intravenous anaesthesia with short-acting drugs. Continuous infusion of remifentanil for postoperative analgesia or supplementation of regional anaesthesia requires careful monitoring of vital functions. The economic aspects of TIVA remain to be determined. PMID- 11194383 TI - [Anesthesia with remifentanil combined with desflurane or sevoflurane in lumbar intervertebral disk operations]. AB - Recovery characteristics, haemodynamic profile, analgesic requirement and costs were evaluated and compared in patients undergoing elective lumbar discectomy with remifentanil-based anaesthesia using either desflurane or sevoflurane as the volatile anaesthetic agent. Sixty-two patients (ASA I/II status) were randomly assigned to receive either desflurane and remifentanil or sevoflurane and remifentanil (in oxygen/air) for anaesthesia. After induction with 0.5 microgram/kg/min remifentanil, 4 to 5 mg/kg thiopentone and 0.5 mg/kg atracurium, the patients received 0.25 microgram/kg/min remifentanil and 0.5 +/- 0.05 MAC of one of the volatile anaesthetic agents for further maintenance of anaesthesia. At the end of surgery, early emergence from anaesthesia was recorded by assessing the time to sufficient spontaneous respiration, eye opening and tracheal extubation. The total demand of piritramide in the postoperative period was determined using patient-controlled analgesia (PCA device). Quality of pain therapy was assessed via a verbal ranking scale (VRS). Side-effects such as postoperative nausea, vomiting or shivering were recorded in the postanaesthetic care unit. In both groups, the haemodynamic profile was nearly identical. Mean arterial pressure (-18%) and heart rate (-23%) were significantly reduced throughout anaesthesia in both groups. All recovery parameters were significantly shorter in the desflurane group in comparison with the sevoflurane group (e.g. time to tracheal extubation: 8.5 +/- 3.0 min vs. 11.9 +/- 4.6 min). No significant differences between the groups were observed concerning the amount of piritramide required, side-effects such as nausea and vomiting or the total cost of anaesthesia. In conclusion, both anaesthetic techniques provide adequate haemodynamic stability and postoperative pain control in a surgical procedure with minimal trauma. Incidence and severity of side-effects such as nausea, vomiting or shivering did not differ between the groups and were acceptable under clinical conditions. Costs for desflurane were significantly higher than those for sevoflurane, but total costs were not different between the groups. Concerning recovery profile, desflurane/remifentanil seems to have small advantages over sevoflurane/remifentanil in patients undergoing lumbar vertebral disc resection. PMID- 11194384 TI - [Continuous recording of cardiac output volume with the OptiQ system--experiences with clinical application]. AB - This report discusses initial experiences with the clinical application of continuous cardiac output measurement (OptiQ SvO2/CCO-System). The system was used in 9 intensive care patients suffering either global cardiac insufficiency or systemic inflammatory response syndrome. Continuous cardiac output measurement was recorded during a period of stable blood pressure conditions and compared with the results of the conventional thermodilution method (bolus technique) in these patients. Regression analyses yielded r = 0.523 (r2 = 0.274) for the "urgent" mode, r = 0.943 (r2 = 0.889) for the "fast" mode, r = 0.953 (r2 = 0.907) for the "fast filter" mode and r = 0.990 (r2 = 0.980) for the "normal" mode. Mean differences between the continuous and the bolus technique were calculated as 0.13 +/- 1.81 l/min for the "urgent" mode, -0.42 +/- 0.51 l/min for the "fast" mode, -0.14 +/- 0.48 l/min for the "fast filter" mode and -0.08 +/- 0.19 l/min for the "normal" mode. After a period of two days, the costs of the conventional bolus technique significantly exceeded those of continuous measurement. The expenses for the conventional thermodilution technique are largely determined by the frequency of application and, hence, by the personnel and laboratory costs. In our experience, easy component handling and stable measuring properties make this new method of continuous cardiac output monitoring a valuable method in the diagnose and care of patients who are critically ill. PMID- 11194385 TI - Distance learning--an educational tool for developing countries. AB - Many anaesthetists in small hospitals and developing countries have poor access to educational materials. The use of electronic means of publication and distribution, combined with the concepts of distance learning, can lead to better levels of knowledge and clinical practice. A project based on these principles has been set up in Zimbabwe, and is proving helpful to both trainers and trainees. All District Hospitals have been visited, and trainees in them identified. A survey has been completed to identify the subject areas in which training is most necessary. Trainees have been provided with reference materials on CD-ROM which they can access by computer (each hospital has a computer). Specialist anaesthesiologists in the country are producing interactive tutorials which can be sent out by e-mail to every hospital, and these are backed up by a programme of regular visits, seminars and clinical teaching. The programme is proving helpful to both trainees and tutors, and has the potential to be used in the future in other developing countries. PMID- 11194386 TI - Outrageous II. PMID- 11194387 TI - Now is the time to observe and treat dental occlusion. PMID- 11194388 TI - Courts conflict over ERISA pre-emptions. PMID- 11194389 TI - Missing posterior teeth. PMID- 11194390 TI - Dental waterline filters. PMID- 11194391 TI - Alternate benefits. PMID- 11194392 TI - Proper terms. PMID- 11194393 TI - Parallel posts. PMID- 11194395 TI - Medication misuse is prevalent. PMID- 11194394 TI - Journal unveils new look, new features; prepares to go online. PMID- 11194396 TI - Home security in a broadband world. PMID- 11194397 TI - Macroesthetic elements of smile design. AB - BACKGROUND: Clinicians' expanding use of cosmetic restorative procedures has generated greater interest in the determination of esthetic guidelines and standards. The overall esthetic impact of a smile can be divided into four specific areas: gingival esthetics, facial esthetics, microesthetics and macroesthetics. In this article, the authors focus on the principles of macroesthetics, which represents the relationships and ratios of relating multiple teeth to each other, to soft tissue and to facial characteristics. CASE DESCRIPTION: The authors categorize macroesthetic criteria based on two reference points: the facial midline and the amount and position of tooth reveal. The facial midline is a critical reference position for determining multiple design criteria. The amount and position of tooth reveal in various views and lip configurations also provide valuable guidelines in determining esthetic tooth positions and relationships. CLINICAL IMPLICATIONS: Esthetics is an inherently subjective discipline. By understanding and applying simple esthetic rules, tools and strategies, dentists have a basis for evaluating natural dentitions and the results of cosmetic restorative procedures. Macroesthetic components of teeth and their relationship to each other can be influenced to produce more natural and esthetically pleasing restorative care. PMID- 11194398 TI - Ask the expert. Will ceramic restorations be challenged in the future? PMID- 11194399 TI - Clinical implications of sex in acute temporomandibular disorders. AB - BACKGROUND: Previous research on temporomandibular disorders, or TMDs, has been somewhat limited, with studies having low numbers of subjects, restricting the focus to women or looking at patients already diagnosed with chronic TMD. Because early intervention is beneficial, it is important to understand the symptoms that men and women have in the acute stage of TMD. METHODS: A total of 233 patients (161 women, 72 men) with acute TMD symptoms were assessed with a battery of biopsychosocial measures. Patients were diagnosed as having TMD on the basis of research diagnostic criteria, or RDC, or RDC, for TMD. After six months, patients were reassessed to determine whether they continued to have pain, thus classifying them as having chronic TMD. The authors found that 153 patients (47 men, 106 women) had developed a chronic condition, while 80 patients (25 men, 55 women) no longer reported pain (nonchronic). RESULTS: Female and male patients who developed chronic TMD differed significantly from patients who had acute symptoms that subsided. Women who developed chronic TMD exhibited significantly more psychosocial distress and impairment than women who did not develop chronic TMD, in terms of Diagnostic and Statistical Manual, Fourth Edition, or DSM-IV, diagnoses; Beck Depression Inventory, or BDI, scores; Minnesota Multiphasic Personality Inventory scores; Multidimensional Pain Inventory, or MPI, scores; and physical and psychological measures assessed with the RDC for TMD. Men who developed chronic TMD differed significantly from men who did not develop chronic TMD, in that they exhibited more impairment in terms of DSM-IV diagnoses and BDI and RDC measures. CONCLUSIONS: These findings provide evidence that significant differences exist between men and women in regard to acute TMD symptoms. CLINICAL IMPLICATIONS: The biopsychosocial differences between men and women suggest that some treatments may be more beneficial for women than for men. PMID- 11194400 TI - Potential health and environmental issues of mercury-contaminated amalgamators. AB - BACKGROUND: Dental amalgamators may become contaminated internally with metallic mercury. This contamination may result from mercury leakage from capsules during trituration or from the long-term accrual from microscopic exterior contaminants that result from the industrial assembly process. The potential health risk to dental personnel from this contamination is unknown. METHODS: The authors assessed used amalgamators from the federal service inventory for the amounts of mercury vapor levels, as well as the visual presence of mercury contamination. They evaluated these amalgamators for potential mercury vapor health risk, using established National Institute for Occupational Safety and Health methods and American Conference of Governmental Industrial Hygienists standards. RESULTS: Ten of the 11 amalgamators assessed had measurable mercury vapor levels. Four amalgamators were found to have internal static mercury vapor levels above Occupational Safety and Health Administration ceiling limit thresholds. During a simulated worst-case clinical use protocol, the authors found that no amalgamators produced mercury vapor in the breathing space of dental personnel that exceeded established time-weighted federal mercury vapor limits. CONCLUSIONS: Amalgamators may be contaminated internally with metallic mercury. Although the authors detected mercury vapor from these units during aggressive, simulated clinical use, dilution factors combined with room air exchange were found to keep health risks below established federal safety thresholds. CLINICAL IMPLICATIONS: Dental personnel should be aware that amalgamators may be contaminated with mercury and produce minute amounts of mercury vapor. These contaminated amalgamators may require disposal as environmentally hazardous waste. PMID- 11194401 TI - Perspectives of Maryland dentists on oral cancer. AB - BACKGROUND: Maryland's mortality rate for oral and pharyngeal cancer is seventh highest overall in the United States, sixth highest for men and third highest for African-American men. As part of a statewide needs assessment and in follow-up to a mail survey of Maryland general dentists, focus groups were conducted to obtain more in-depth information about why dentists do not provide a comprehensive oral cancer examination for most of their patients and how to solve this problem from a dentist's perspective. METHODS: A trained focus group moderator conducted two focus groups of general practice dentists in two locations in Maryland. Five major themes emerged from the two focus groups: inaccurate knowledge about oral cancer; inconsistency in oral cancer examinations; lack of confidence in when and how to palpate for abnormalities; lack of time to routinely provide oral cancer examinations; and recommendations to help resolve these issues. CONCLUSIONS: The focus groups provided a rich source of ideas on how to best provide dentists with continuing education about oral cancer prevention and early detection. Participants also provided opinions about the need to improve the public's awareness of oral cancer and its prevention. CLINICAL IMPLICATIONS: Dentists need to include comprehensive oral cancer examinations as part of their routine oral examinations for all appropriate patients. PMID- 11194402 TI - Using notched tray modification for accurate double-arch impressions. PMID- 11194403 TI - Utilization of library outreach services by dental school alumni, 1988-1998. AB - BACKGROUND: The University of Missouri-Kansas City School of Dentistry Library outreach service includes the Dental Reference Service, or DRS; Loansome Doc service, Career Opportunity Center, or COC; and the Instructional Resources Library, or IRL. The author reviewed usage of services for 1988-1998 to analyze use by alumni and nonalumni and to determine possible trends. METHODS: The author reviewed the UMKC School of Dentistry Library outreach service database from 1988 1998 to determine the total number of contacts for all services, numbers of contacts for each service, overall number of items sent and the number of dental health professionals contacting the services. RESULTS: The author found that the COC received 55 percent of contacts for the years 1988-1998, while the DRS received 26 percent of the total contacts and the IRL service received 19 percent. The DRS had the highest usage by alumni (80 percent); Loansome Doc service accounted for 11 percent of the DRS contacts. Total number of items sent in response to all requests was 34,325, of which 22,647 (66 percent) were to alumni. Alumni usage of all outreach services was consistent, ranging from 54 to 63 percent of the total. CONCLUSIONS: It appears that UMKC School of Dentistry alumni are active information-seekers. Several questions, however, remain, indicating that additional research should be done in the area of dental informatics. PRACTICE IMPLICATIONS: Information-seeking behaviors are an important part of the active clinical practice and may become more important as evidenced-based dentistry becomes more prevalent. PMID- 11194404 TI - Ask the expert. What are the diagnostic protocols for oral cancer screenings? PMID- 11194405 TI - Dentists' attitudes and behaviors regarding domestic violence. The need for an effective response. AB - BACKGROUND: The authors examined the attitudes and behaviors of a national sample of dentists regarding domestic violence and the barriers dentists face in intervening to help victims. METHODS: The authors surveyed a national random sample of 321 dentists by mail from November 1997 to March 1998 about their attitudes and clinical practice behaviors related to domestic violence. Survey items were developed based on the domestic violence and health care literature. The authors used the Total Design Method to maximize the response rate and analyzed data to determine differences between dentists who had received domestic violence education and those who had not. RESULTS: Eighty-seven percent of responding dentists never screened for domestic violence; 18 percent never screened even when patients had visible signs of trauma on their heads or necks. Overall, respondents intervened only minimally to help patients whom they had identified as victims. Respondents reported that the major barriers to screening were the presence of a partner or children (77 percent), lack of training (68 percent), concern about offending patients (66 percent) and their own embarrassment about bringing up the topic of abuse (51 percent). Respondents who had received domestic violence education were significantly more likely to screen for domestic violence and to intervene. CONCLUSIONS: Dentists face many barriers to identifying and helping patients who are abuse victims, yet these data suggest that education about domestic violence could help them overcome some of these barriers. CLINICAL IMPLICATIONS: We suggest that dentists follow the AVDR model when approaching abused patients in their practice: Ask about abuse, provide Validating messages, Document presenting signs and Refer victims to domestic violence specialists. PMID- 11194407 TI - Brain activity and cognitive processes: introduction to the special issue. PMID- 11194406 TI - Anticalculus efficacy of an antiseptic mouthrinse containing zinc chloride. AB - BACKGROUND: The authors undertook a controlled clinical study to determine the efficacy of a tartar-control antiseptic mouthrinse in inhibiting the development of supragingival dental calculus. METHODS: After undergoing a dental prophylaxis, 334 subjects with a moderate rate of calculus formation were stratified and randomly assigned to one of three groups: positive control (using a tartar control toothpaste and an antiseptic rinse), negative control (using a regular toothpaste and an antiseptic mouthrinse) or experimental (using a regular dentifrice and a tartar-control mouthrinse). Subjects brushed and rinsed twice daily, unsupervised, for four months. The researchers assessed subjects' calculus levels using the Volpe-Manhold Index, or VMI, after 16 weeks. RESULTS: Using analysis of covariance, the authors found that both the experimental group (which used a tartar-control rinse containing zinc chloride) and the positive control group (which used a tartar-control dentifrice containing pyrophosphate) demonstrated statistically significantly lower VMI scores (P = .001) than the negative control group (which used a regular dentifrice and an antiseptic rinse). Both anticalculus agents provided a clinically relevant 21 percent reduction in calculus formation. CONCLUSION: An antiseptic mouthrinse containing 0.09 percent zinc chloride as the anticalculus agent provides a clinically relevant reduction in calculus formation in people with a moderate rate of such formation. CLINICAL IMPLICATIONS: A tartar-control mouthrinse with zinc chloride as the tartar control ingredient is clinically effective in reducing the formation of calculus. PMID- 11194408 TI - Cognitive neuroscience of episodic memory encoding. AB - This paper presents a cognitive neuroscientific perspective on how human episodic memories are formed. Convergent evidence from multiple brain imaging studies using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) suggests a role for frontal cortex in episodic memory encoding. Activity levels within frontal cortex can predict episodic memory encoding across a wide range of behavioral manipulations known to influence memory performance, such as those present during levels of processing and divided attention manipulations. Activity levels within specific frontal and medial temporal regions can even predict, on an item by item basis, whether an episodic memory is likely to form. Furthermore, separate frontal regions appear to participate in supplying code-specific information, including distinct regions which process semantic attributes of verbal information as well as right-lateralized regions which process nonverbal information. We hypothesize that activity within these multiple frontal regions provides a functional influence (input) to medical temporal regions that bind the information together into a lasting episodic memory trace. PMID- 11194409 TI - Individual differences in the functional neuroanatomy of verbal discrimination learning revealed by positron emission tomography. AB - Why do some people have better memory abilities than others? This issue has been of long-standing interest to scientists and lay people. However, using purely behavioral methods, psychologists have made little progress in illuminating it. Now that functional brain imaging techniques have become available to study mind/brain relations, there is a new promise of understanding individual differences in learning and memory in terms of corresponding differences in brain activity. In this paper, we will present a positron emission tomography (PET) study designed to examine individual differences in learning and memory abilities. The basic assumption is that different patterns of brain activity serve as strong predictors of memory performance. Two specific questions were addressed in this study: (i) Can PET illuminate the relations between memory processes and their neuroanatomical correlates among individual learners and rememberers? and (ii) if so, how are these relations affected by the stage of practice on a given memory task? Our PET study examined individual differences in the neuroanatomical correlates of multi-trial verbal discrimination learning in 16 young healthy subjects. The results identified patterns of brain regions in which blood flow correlated with subjects' retrieval performance. However, these regions did not correlate with performance during all learning trials. Instead, a gradual shift was observed from one pattern of brain regions to another over the course of learning. These results suggest that individual differences in memory performance are related to differences in neural activity within specific brain circuits. PMID- 11194410 TI - Episodic encoding and recognition of pictures and words: role of the human medial temporal lobes. AB - In the present PET study, we examined brain activity related to processing of pictures and printed words in episodic memory. Our goal was to determine how the perceptual format of objects (verbal versus pictorial) is reflected in the neural organization of episodic memory for common objects. We investigated this issue in relation to encoding and recognition with a particular focus on medial temporal lobe (MTL) structures. At encoding, participants saw pictures of objects or their written names and were asked to make semantic judgments. At recognition, participants made yes-no recognition judgments in four different conditions. In two conditions, target items were pictures of objects; these objects had originally been encoded either in picture or in word format. In two other conditions, target items were words; they also denoted objects originally encoded either as pictures or as words. Our data show that right MTL structures are differentially involved in picture processing during encoding and recognition. A posterior MTL region showed higher activation in response to the presentation of pictures than of words across all conditions. During encoding, this region may be involved in setting up a representation of the perceptual information that comprises the picture. At recognition, it may play a role in guiding retrieval processes based on the perceptual input, i.e. the retrieval cue. Another more anterior right MTL region was found to be differentially involved in recognition of objects that had been encoded as pictures, irrespective of whether the retrieval cue provided was pictorial or verbal in nature; this region may be involved in accessing stored pictorial representations. Our results suggest that left MTL structures contribute to picture processing only during encoding. Some regions in the left MTL showed an involvement in semantic encoding that was picture specific; others showed a task-specific involvement across pictures and words. Together, our results provide evidence that the involvement of some but not all MTL regions in episodic encoding and recognition is format specific. PMID- 11194411 TI - Brain activation during episodic memory retrieval: sex differences. AB - Behavioral studies have shown a tendency for women to outperform men on episodic memory tasks. Here, data from a series of positron emission tomography (PET) studies were analyzed to examine sex differences in brain activity associated with episodic memory retrieval (yes/no recognition). A total of 17 women and 17 men were included in the analyses. The strongest effect of the design was a retrieval-related increase in activity, involving right prefrontal and anterior cingulate regions, that was common to women and men. In addition, a significant task-by-sex interaction effect was observed which involved a distributed set of brain regions, including several frontal areas. These results suggest that while the neural correlate of episodic memory retrieval is largely the same for men and women, some differences do exist. Possible explanations for the observed differences are discussed, and it is concluded that biological and experiential factors jointly contribute to sex differences in brain activity. PMID- 11194412 TI - When, where, what: the electromagnetic contribution to the WWW of brain activity during recognition. AB - Recent findings from event-related potential (ERP) as well as hemodynamic studies have provided physiological evidence that recognition memory involves task related brain processes, notably episodic retrieval mode, and item-related brain processes, notably retrieval success or ecphory. The excellent time resolution of electromagnetic techniques allows to study the time course of these processes on a time range from milliseconds to several seconds. In a series of studies, the time scales within which task- and item-related processes are likely to operate were investigated. The results raise the possibility that both types of processes are further fractionable into short and longlasting components. The cognitive underpinnings of these components have yet to be determined. PMID- 11194414 TI - The cognitive neuroscience of signed language. AB - The present article is an assessment of the current state of knowledge in the field of cognitive neuroscience of signed language. Reviewed lesion data show that the left hemisphere is dominant for perception and production of signed language in aphasics, in a fashion similar to spoken language aphasia. Several neuropsychological dissociations support this claim: Non-linguistic visuospatial functions can be dissociated from spatial functions and general motor deficits can be dissociated from execution of signs. Reviewed imaging data corroborate the lesion data in that the importance of the left hemisphere is re-confirmed. The data also establish the role of the right hemisphere in signed language processing. Alternative hypotheses regarding what aspects of signed language processing are handled by the right hemisphere are currently tested. The second section of the paper starts by addressing the role that early acquisition of signed and spoken language play for the neurofunctional activation patterns in the brain. Compensatory cognitive and communicative enhancements have also been documented as a function of early sign language use, suggesting an interesting interaction between language and cognition. Recent behavioural data on sign processing in working memory--a cognitive system important for language perception and production suggest e.g. phonological loop effects analogous to those obtained for speech processing. Neuroimaging studies will have to address this potential communality. PMID- 11194413 TI - Lateralization of cognitive processes in the brain. AB - The lateralization of cognitive processes in the brain is discussed. The traditional view of a language-visuo/spatial dichotomy of function between the hemispheres has been replaced by more subtle distinctions. The use of magnetic resonance imaging (MRI) to study brain morphology has resulted in a renewed focus on the relationship between structural and functional asymmetry. Focus has been on the role played by the planum temporale area in the posterior part of the superior temporal gyrus for language asymmetry, and the possible significance of the larger left planum. The dichotic listening technique is used to illustrate the difference between bottom-up, or stimulus-driven laterality versus top-down, or instruction-driven laterality. It is suggested that the hemispheric dominance observed at any time is the sum result of the dynamic interaction between bottom up and top-down processing tendencies. Stimulus-driven laterality dominance is always monitored and modulated through top-down cognitive processes, like shifting of attention and changes in arousal. A model of top-down modulation of bottom-up laterality is presented with special reference to the understanding of psychiatric disorders. PMID- 11194415 TI - Functional brain imaging as a looking-glass into the degraded brain: reviewing evidence from Alzheimer disease in relation to normal aging. AB - Research on the real-time relationship between brain activity and mental performance is intense. However, relatively few studies have been devoted to patients with different diseases or lesions. Such studies may cast light on certain aspects of brain activity, such as plasticity. This review summarizes studies on Alzheimer's disease (AD) patients where the techniques to map brain activity in relation to mental performance have been utilized. Research findings suggest, that there is a spectrum of changes in AD patients that is distinct from that seen in healthy aging. These changes include: (i) loss of activated regions, (ii) reduced activation possibly due to brain degeneration typical of AD, (iii) the emergence of newly activated regions in order to compensate for minor brain deterioration (e.g., an enlargement of activated regions sometimes manifested as an increased bilaterality or a hemispheric shift of activation, and dedifferentiation), (iv) decreased level of activation, and (v) no change at all, which may occur in easy tasks or tasks that do not involve regions exposed to brain atrophy. In conclusion, the pattern of activation in AD depends on interactions between the clinical stage of patients, and the pattern of brain degeneration, as well as the task difficulty and specific networks necessary for solving the task. PMID- 11194417 TI - Noah's new ark. The imminent birth of a cloned gaur signals a new approach to preservation. PMID- 11194416 TI - The potent perils of a miracle drug. PMID- 11194418 TI - Feel no pain. What you need to know about the new rules for treating pain at hospitals and other facilities. PMID- 11194419 TI - The new biology and human reproduction. PMID- 11194420 TI - Antenatal transfer of rural women to perinatal centres. High Risk Obstetric and Perinatal Advisory Working Group. AB - The aim of this study was to describe antenatal transfers of rural women to perinatal centres, and among transferred women, to assess the use of selected evidence-based therapies and determine the predictors of preterm and imminent births. The clinical records of rural women antenatally transferred to perinatal centres in NSW and the ACT during 1997-1998 were reviewed. Of 453 rural antenatal transfers, 408 (90%) were emergency transfers. Increasing remoteness was associated with increased rates of antenatal transfer but not with a lower probability of giving birth. Of all transferred women, 64% delivered; 58% of preterm transfers delivered preterm and of those delivering preterm, 76% delivered within 7 days. Although the main reason for antenatal transfer was the possibility of preterm birth, women presenting with preterm contractions only were less likely to deliver preterm (OR = 0.2, 95% CI 0.1-0.4) or < or = 7 days (OR = 0.3, 95% CI 0.2-0.5) than women with any other presenting symptoms. The overall usage of effective interventions (antenatal steroids, antibiotics for PPROM and beta-mimetic tocolysis to delay birth) among antenatally transferred rural women was high, but there is room for increased uptake prior to transfer. PMID- 11194421 TI - Fetal growth charts for Aboriginal fetuses. AB - The study aimed to determine whether fetal growth parameters in Aboriginal pregnancies are such that separate fetal growth charts are necessary for their appropriate care. We designed a prospective study of a cohort of Aboriginal women presenting for antenatal care before 20 weeks gestation (ultrasound proven) and a reference cohort of Caucasian women. Four remote North Queensland communities served by the Far North Regional Obstetric and Gynaecological Service (FROGS) and the antenatal clinic at Cairns Base Hospital took part in the survey One hundred and four Aboriginal and 101 Caucasian women with no known medical factors affecting fetal growth or gestation were recruited, and 96 Aboriginal and 96 Caucasian women completed the study Measurements took the form of longitudinal percentile charts of fetal biparietal diameter, abdominal circumference and femur length. Ultrasound measurements of fetal biparietal diameter, abdominal circumference and femur length were obtained 3 to 5 times during Aboriginal and Caucasian pregnancies, where the gestation was established by ultrasound before 20 weeks gestation, and no known medical conditions which affect fetal growth were present in the mother. There were no statistical or clinically important differences in biparietal diameter, femur length and abdominal circumference of Aboriginal and Caucasian fetuses. We concluded that there is no reason to use separate fetal growth charts when examining Aboriginal fetal growth. PMID- 11194422 TI - The impact of nausea and vomiting on women: a burden of early pregnancy. AB - Nausea and vomiting are troublesome symptoms occurring in the first trimester of pregnancy. The aim of this study was to describe the impact these symptoms have on women in early pregnancy by interviewing, using a structured questionnaire, 593 pregnant women presenting with nausea and vomiting in the first trimester of pregnancy. The women were asked to complete the Rhodes index of nausea and vomiting and the MOS 36 Short Form Health Survey (SF-36). Symptoms of nausea and vomiting started early in pregnancy. Nausea was the most troublesome symptom experienced by women, both in its duration and intensity. Low scores for the SF 36 were found for all items, particularly physical functioning, energy and social functioning. The women described substantial effects on working, household duties and parenting activities. Findings from this study suggest nausea and vomiting in early pregnancy has a profound impact on women's general sense of well-being and day to day life activities. PMID- 11194423 TI - Preoperative diagnosis of dehiscence of the lower uterine segment in patients with a single previous Caesarean section. AB - Preoperative diagnoses were checked during surgery in 39 patients who underwent elective repeat Caesarean section with (n = 20) and without (as control, n = 19) a preoperative diagnosis of wall dehiscence (thinning) of the lower uterine segment (LUS). All patients were examined manually and by ultrasonography at 36 weeks gestation before labour. A preoperative diagnosis of wall dehiscence was made when the wall thickness was less than 2 mm and/or the patient felt pain and tenderness in the LUS. Surgical findings of dehiscence were defined as a subperitoneal separation of the uterine scar in the LUS. The sensitivity and specificity of our ultrasonographic evaluations were found to be 100% and 83% (p < 0.05), respectively. On the other hand, there were no surgical findings of dehiscence in patients who felt pain and tenderness in the LUS with a wall thickness greater than 2 mm, nor among those in the control group. PMID- 11194424 TI - Perimortem Caesarean section: two case reports and a management protocol. AB - Perimortem Caesarean section is a rare clinical event. Two cases are reported. Both cases had poor outcomes. The impact of this was traumatic for the trainee specialists who managed the two cases. The relevant literature has been reviewed and a protocol for the management of this rare emergency is presented. PMID- 11194425 TI - Improving antenatal recognition of women at risk for postnatal depression. AB - The purpose of this study was to assess the effectiveness of a practical antenatal screen used at the Royal Women's Hospital, Brisbane, to identify women at risk for postnatal depression. It was a prospective, hospital-based, cohort study of 901 women (600 with and 301 without prenatal risk factors for postnatal depression). Depression was measured 16 weeks after the birth using the Edinburgh Postnatal Depression Scale. More of the women with a prenatal risk factor for depression (25.9%) scored above 12 on the Edinburgh Postnatal Depression Scale than those without any risk (10.9%) (p < or = 0.001). Low social support (p < or = 0.001), a personal history of mood disorder (p < or = 0.001) and a past history of postnatal depression ( p = 0.002) were all strongly associated with postnatal depression in this sample. Results indicate that an objective, psychosocial assessment during pregnancy improves recognition of women at risk for postnatal depression. PMID- 11194426 TI - Contemporary management of epilepsy in pregnancy. PMID- 11194427 TI - A randomised controlled trial of dietary energy restriction in the management of obese women with gestational diabetes. AB - A randomised controlled trial was designed to determine the effect of moderate 30% maternal dietary energy restriction on the requirement for maternal insulin therapy and the incidence of macrosomia in gestational diabetes. Although the control group restricted their intake to a level similar to that of the intervention group (6,845 kiloJoules (kJ) versus 6,579 kJ), the resulting cohort could not identify any adverse effect of energy restriction in pregnancy. Energy restriction did not alter the frequency of insulin therapy (17.5% in the intervention group and 16.9% in the control group). Mean birthweight (3,461 g in the intervention group and 3,267 g in the control group) was not affected. There was a trend in the intervention group towards later gestational age at commencement of insulin therapy (33 weeks versus 31 weeks) and lower maximum daily insulin dose (23 units versus 60 units) which did not reach statistical significance. Energy restriction did not cause an increase in ketonemia. PMID- 11194428 TI - The utilisation of nuchal translucency as a prenatal marker of Down syndrome, 1993-1999. AB - A sample of 6,038 obstetric ultrasound referrals and reports between January 1993 and June 1999 in a single Melbourne private ultrasound practice was reviewed to determine whether the referral and reporting pattern for nuchal translucency (NT) measurement has changed. The proportion of both 10-14 week ultrasound scans and mid trimester fetal anatomy scan referrals increased significantly over the study period (p < 0.001 and p < 0.001, respectively). There was also a significant increase in NT reporting and the number of specific referrals for an NT measurement over the study period (p = 0.01 and p < 0.001, respectively). If current trends continue it is likely that the 10-14 week scan for NT measurement will become a routine component of antenatal care. Therefore, as a matter of urgency, it is imperative that the best and most cost-effective screening strategy for Down syndrome in an Australian population is defined. PMID- 11194429 TI - Parental decision-making differences between patients in two healthcare systems for choroid plexus cysts. AB - We evaluated the medical-sociological implications of parental perception of risk and decision-making choices for prenatally ascertained choroid plexus cysts (CPC) between two obstetric populations. The Wayne State University (WSU) Reproductive Genetics database and the Madigan Army Medical Center (MAMC) experience were reviewed to compare the rates of aneuploidy and invasive testing for cases with CPC. Aneuploidy rates were compared between those with isolated CPC, CPC with advanced maternal age (AMA), and CPC associated with multiple anomalies. In the WSU cohort 186 cases were identified, of whom 27 (15%) declined invasive fetal testing. In the remaining 159 cases, aneuploidy was present in 2/132 (1.5%) isolated CPC, 3/11 (27%) CPC with AMA, and 15/16 (93%) CPC with multiple anomalies. In the MAMC cohort 107 cases were identified, of whom 99 (92%) declined invasive fetal testing. No aneuploidy cases were found in the 3/12 AMA cases or 5/95 non-AMA cases that underwent amniocentesis. The two cases of aneuploidy with isolated CPC cannot be ignored, and provide an estimated attributable risk of at least 0.8%, a higher risk than 38 years of age. However, the parental sociologic context may be as important for decision-making as the genetic-prognostic risk. PMID- 11194430 TI - Management of vaginal agenesis: review of 10 years practice at a tertiary referral centre. AB - Vaginal agenesis is an uncommon congenital anomaly, and is often associated with agenesis of the uterus and fallopian tubes. Recent reports suggest that non surgical methods to create a neovagina offer advantages when assisted reproductive treatments are used in the adult life of these women. We have reviewed the management of 39 women with congenital vaginal agenesis to assess the outcomes of neovaginal creation. In 25 women with total Mullerian agenesis, creation of a neovagina using progressive perineal dilatation alone was very successful in women motivated by a sexual relationship. PMID- 11194432 TI - An experience with transvaginal sonography in gynaecologic tumour surveillance. AB - Surveillance of gynaecologic cancer patients treated with a curative intent involves frequent presentations by the patient for a targeted history, detailed general and pelvic examination, including Pap smear. One of the aims of such surveillance is to detect potentially curable recurrences early to allow the initiation of further therapy, hopefully to attain eradication of the recurrent tumour. Six cases are presented where the prudent use of transvaginal sonography (TVS) was found to be useful in the exclusion of recurrent tumour in patients with symptoms; early diagnosis in patients who were asymptomatic; confirmation of disease in those with symptoms; to evaluate patients with obliterated upper vaginas due to therapy, and follow-up of those with confirmed recurrence as a form of disease marker. PMID- 11194431 TI - Pain relief following day case laparoscopic tubal ligation with intra-peritoneal ropivacaine: a randomised double blind control study. AB - The aim of this study was to examine the effectiveness of ropivacaine administered by a simple intraperitoneal technique in relieving pain following laparoscopic application of Filshie clips. Nineteen patients were randomised to receive either ropivacaine (200 mg) or normal saline through the umbilical port following clip application. Using a visual analogue scale women receiving ropivacaine had significantly lower pain scores 2 hours post operatively (0.97 vs 2.03 p < 0.05). The mean total postoperative fentanyl use was also significantly lower on the ropivacaine group (40 microg vs 104 microg p < 0.02). Only 10% (1/10) of the women in the ropivacaine group complained of nausea compared with 44% (4/9) in the control group. Furthermore, 80% (8/10) of women in the ropivacaine group were either very or totally satisfied with their pain relief. Only 56% (5/9) of the women in the control group were very or totally satisfied with their pain relief. Ropivacaine administered by a simple intraperitoneal technique following laparoscopic sterilisation significantly reduces postoperative pain and parenteral analgesic requirements. It would be reasonable to consider this method as standard practice following laparoscopic tubal ligation. PMID- 11194433 TI - Body image and psychological well-being in pregnancy. A comparison of exercisers and non-exercisers. AB - This study compared the perceptions of body image and psychological well-being between exercising and non-exercising pregnant women. A prospective longitudinal study was conducted with 65 nulliparous women (mean age years = 30.3, range = 23 39) who were allocated to 2 groups based on level of recreational exercise participation; 25 exercisers were compared with 18 non-exercisers. A self-report exercise history questionnaire and a 10 item Body Cathexis Scale were completed on two occasions during the pregnancy, at approximately 17 weeks and 30 weeks of gestation. The General Health Questionnaire (GHQ-28) was administered in late pregnancy. There was a significant difference between the exercise group and the non-exercise group in late pregnancy for some items on the Body Cathexis Scale. The exercise group had a lower level of probable caseness on the GHQ-28 with reduced frequency of somatic symptoms, anxiety and insomnia, and a higher level of psychological well-being. PMID- 11194434 TI - Changes in the plasma activities of protein C and protein S during pregnancy. AB - The objective of the study was to determine the changes in the plasma activities of protein C and protein S that occur during normal pregnancy In this prospective cross-sectional study, plasma activities of protein C and protein S were measured in 32 normal pregnant women in the first, second and third trimester and 6 weeks after delivery There was a significant fall in protein C and protein S activities during normal pregnancy compared with the post-puerperal period. The activities of protein C and protein S also gradually decreased throughout pregnancy (p < 0.01). Increasing plasma volume during normal pregnancy and its dilutional effect might play some role in the low activities of protein S observed. The normal falls in protein S and protein C activities make it difficult to diagnose protein S and C deficiency during pregnancy. Based on our findings, if a woman has a thromboembolic event during pregnancy, testing for a definitive diagnosis of protein C or protein S deficiency or functional failure should be delayed until at least 6 weeks postpartum. PMID- 11194435 TI - Tissue kallikrein activity in pregnancy. AB - To determine tissue kallikrein (TK) activity in black African women with hypertensive disorders of pregnancy; 140 women were recruited and divided into the following groups: group A--35 preeclamptic women, group B--35 mild to moderate hypertensive pregnant women and group C--35 normotensive pregnant women, and group D--35 normotensive non-pregnant healthy women. The activity of tissue kallikrein was determined from a random untimed urine sample using a selective, synthetic chromogenic tripeptide substrate having the sequence H-D-Val-Leu-Arg pNA (S-2266). Urinary sodium and potassium levels was determined by flame photometry. Tissue kallikrein activity was decreased in women with preeclampsia (1.54 +/- 0.95 vs 3.05 +/- 0.83 ngTK/microg protein; p < 0.0001) and mild to moderate hypertensive group (2.03 +/- 0.76 vs 3.05 +/- 0.83 ngTK/microg protein; p < 0.0001) compared with normotensive pregnant women. There was also a significant difference in tissue kallikrein activity between the pregnancy groups (1.54 +/- 0.95 vs 2.03 +/- 0.76 ngTK/microg protein; p < 0.001). No difference in tissue kallikrein activity was observed between normotensive pregnant and normotensive non-pregnant healthy women (3.05 +/- 0.83 vs 3.14 +/- 0.88 ngTK/microg protein; p = 0.51). There was no difference in the excretion of urinary sodium and potassium in pregnancy groups compared to normotensive pregnant group. Tissue kallikrein activity is decreased in hypertensive disorders of pregnancy. PMID- 11194436 TI - Oophorectomy at the time of surgery for moderate endometriosis: a survey of Australian gynaecologists. AB - The decision to perform bilateral oophorectomy at the time of surgery for endometriosis is dependent upon many factors, one of which is the opinion of the surgeon concerned. At present there is no consensus on this subject, and in an attempt to document current opinion, we performed a postal survey of all Fellows of RANZCOG living within Australia. The questionnaire presented the Fellow with a clinical scenario describing moderate endometriosis, and then asked him/her to select their preferred option for each of a number of anatomical areas. Out of 1,050 questionnaires, 688 (65.5%) were returned. Analysis of these replies suggests that current opinion supports a conservative approach to surgery, with only 27.5% of Fellows electing to perform a hysterectomy in conjunction with bilateral oophorectomy. PMID- 11194437 TI - Ruptured tubal ectopic pregnancy associated with negative qualitative human chorionic gonadotrophin levels. PMID- 11194438 TI - Successful vaginal delivery in a woman with amyoplasia. AB - We report on the pregnancy management of a 22-year-old woman with amyoplasia, the commonest type of arthrogryposis multiplex congenita (AMC). Extrapolating from childhood and adult studies, the majority of cases are likely to be ambulatory and live independent lives as adults. Many females, therefore, would be expected to achieve a pregnancy. There have been several case reports on anaesthetic management for Caesarean section delivery in women with arthrogryposis, but no medical literature exists regarding the likelihood or management of vaginal delivery. This is the first reported case of conservative management of a woman with amyoplasia. A multi-disciplinary team was involved in her care. This involved careful assessment of her suitability for vaginal delivery, possible anaesthetic complications and potential difficulties in caring for an infant at home. Induction of labour at 37 weeks gestation resulted in the successful vaginal delivery of a liveborn healthy male. PMID- 11194439 TI - Spontaneous miscarriage of a cervical pregnancy and continuation of intra-uterine pregnancy following in vitro fertilisation and embryo transfer. PMID- 11194440 TI - Vaginal melanoma masquerading as adenocarcinoma based on cervical cytology: a case report and review of the literature. PMID- 11194441 TI - Self-inflicted penetrating abdominal injury in pregnancy. PMID- 11194442 TI - Carcinoid tumour of the ovary: a multidisciplinary approach? PMID- 11194443 TI - Multiple endocrine neoplasia type IIA (Sipple's syndrome) presenting in pregnancy. PMID- 11194444 TI - Birth of twins using in vitro matured oocytes and cryopreserved semen from a male with carcinoma of the penis. AB - Semen cryopreserved from a male prior to treatment for carcinoma of the penis was used for intra-cytoplasmic sperm injection (ICSI) of in vitro matured (IVM) oocytes, resulting in the birth of healthy, non-identical twin girls. PMID- 11194445 TI - It is possible to perform a sacrospinous colpopexy via the incision of an anterior vaginal repair alone if a posterior repair is not required. PMID- 11194446 TI - A new indication for breech extraction. PMID- 11194447 TI - New indication for breech extraction. PMID- 11194448 TI - Outcome after a pap smear report of low-grade abnormality: a longitudinal comparative study. PMID- 11194449 TI - The Chan et all retrospective study of vacuum versus forceps is really a study of difference of practice and not a study of different instruments. PMID- 11194450 TI - Urethral prolapse in a 7 year old girl. PMID- 11194451 TI - Inflammatory breast cancer survival: the role of obesity and menopausal status at diagnosis. AB - No previous studies have evaluated the effect of body size and menopausal status at diagnosis on survival from inflammatory breast cancer (IBC). We evaluated whether obesity and menopausal status had an impact on IBC survival in a cohort of 177 female IBC patients seen from 1974 to 1993 at The University of Texas MD Anderson Cancer Center. Survival time was defined as time from diagnosis until death or censorship at last date of contact. We categorized women by body size by using the National Institutes of Health/National Heart, Lung, and Blood Institute's definitions of obesity as body mass index ((BMI) = weight in kg/(height in m)2) > or = 30, overweight as 25 < or = BMI < 30kg/m2, and normal/lean as BMI < 25 kg/m2. Cox proportional hazards analysis, adjusting for axillary lymph node involvement and chemotherapy protocol, revealed a modifying effect of menopausal status at diagnosis on the association between obesity and IBC survival (P = 0.02). Relative to postmenopausal women, premenopausal women had significantly worse survival (hazard ratio (HR) = 1.51, 95% confidence interval (CI) = 1.03-2.22). After stratifying by menopausal status, premenopausal obese women had non-significantly better survival than their leaner premenopausal counterparts (HR = 0.63, 95% CI = 0.34-1.15) while postmenopausal obese women had significantly worse survival than their leaner counterparts (HR = 1.86, 95% CI = 1.02-3.40). These findings suggest that factors associated with larger body size at diagnosis may contribute to shorter IBC survival among postmenopausal women but not premenopausal women, who were found to have poorer survival regardless of body size. PMID- 11194452 TI - Preliminary assessment of cognitive function in breast cancer patients treated with tamoxifen. AB - BACKGROUND: Tamoxifen is an anti-estrogen used in the treatment of breast cancer and to reduce the incidence of breast cancer in high risk women. Although the brain is an estrogen target organ and several studies have found a beneficial effect of estrogen on cognitive function, the effect of tamoxifen on cognition has not been reported. Therefore, we initiated a follow-up study of women who had participated in a study of breast cancer to assess the effect of tamoxifen treatment on cognitive function. METHODS: We recruited previously interviewed patients who were cases in a population-based case-control study of 2,653 women with primary breast cancer diagnosed between 1987 and 1996 at ages 55-72 years in Los Angeles County, California, USA. In November 1997, each case was mailed a follow-up questionnaire. Cognitive function was assessed by (1) clock drawing. (2) copying a box drawing, and (3) narrative writing to describe a pictured scene. Women reporting treatment with tamoxifen were categorized as standard-term users (4-5 years), short-term users (< 4 years) or long-term users (6 + years) and compared to never users. Tamoxifen users were also classified as past or current users. Differences in the mean cognitive test scores were tested after adjusting for age, age at diagnosis, stage of disease, radiation therapy, chemotherapy, race, education, marital status, previous use of oral contraceptives, type of menopause, age at last menstrual period, previous use of hormone replacement therapy, and depressive symptoms using analysis of covariance. All p-values for differences in the proportion of women who had errors on the tests are 2-sided and adjusted for age, stage of disease at diagnosis, and chemotherapy. FINDINGS: Information from 1,163 women aged 57-75 years of age was analyzed; 710 had taken tamoxifen. There was little difference between women who had used tamoxifen for the standard five years and never users on the three cognitive tests. However, more women who had used tamoxifen for the standard term reported seeing their physician for memory problems than non-users (3.8% vs 1.5%, p = 0.04). This was especially true for current users of standard term (8.0%, p = 0.003). Current users also had a significantly lower mean complexity score (p = 0.03) on the narrative writing task. No differences were seen between past users and non-users. INTERPRETATION: Our study suggests that current use of tamoxifen may adversely effect cognition. Further study of tamoxifen and cognition is needed so that healthy women considering tamoxifen for the primary prevention of breast cancer have comprehensive information about the side effects of the treatment. PMID- 11194453 TI - Liarozole fumarate (R85246): in the treatment of ER negative, tamoxifen refractory or chemotherapy resistant postmenopausal metastatic breast cancer. AB - Three phase II studies were conducted to determine the efficacy and tolerability of liarozole fumarate (R85246; liarozole), a retinoic acid metabolism blocking agent (RAMBA) and aromatase inhibitor. Additionally, animal experiments in the MNU-induced rat mammary tumor model and in immature ovariectomized rats were conducted to further elucidate liarozole's mechanisms of action. Patients were postmenopausal with either: ER negative disease in first relapse (Group 1: 1n = 16); ER positive or unknown disease refractory to tamoxifen (Group 2; n = 16); ER positive, negative or unknown disease resistant or refractory to chemotherapy (Group 3; n = 27). Treatment was liarozole (150-300mg) twice daily orally until disease progression. Response rates were: 25% in group 1 (95% CI 11.0-52.3%: median duration (MD) 20 months; range 2-36.5); 25% in group 2 (95% CI 11.0-52.3%; MD 6.5 months: range 3.5-38): 11% in group 3 (95% CI 4.2-29.2%; MD 7 months; range 3-8.5). No significant improvement in quality of life scores (FLI-C) was noted. Toxicities observed were predominantly dermatological (skin disorders: 88%; dry mouth/eyes/lips: 69%). Plasma estradiol decreased from mean pre treatment levels of 72.7 pM (9.1-1,839 pM) to below detection (9.2 pM) after 1 month. Liarozole, but not vorozole, partially inhibited estradiol induced uterine hypertrophy and demonstrated dose-dependent anti-tumor effects in the rats, only partially overcome by coadministration of estradiol. The clinical responses observed, together with our preclinical results, confirm liarozole's dual mechanism of action and provide a rationale for further evaluation of RAMBAs in the treatment of breast cancer. PMID- 11194454 TI - Polyadenylic-polyuridylic acid plus locoregional radiotherapy versus chemotherapy with CMF in operable breast cancer: a 14 year follow-up analysis of a randomized trial of the Federation Nationale des Centres de Lutte contre le Cancer (FNCLCC). AB - With a median follow-up of 14 years, the combination of polyadenylic-polyuridylic acid plus locoregional radiotherapy (257 patients) has significantly improved disease-free survival (p = 0.03) and significantly reduced the incidence of metastases (p = 0.04) when compared to CMF alone (260 patients), in women with operable breast cancer. The trial does not, however, permit an appreciation of the respective role of radiotherapy and PolyAU in these results. PMID- 11194455 TI - Selective decrease of serum immunoglobulin G1 as marker for early stages of invasive breast cancer. AB - The diagnostic value of the decrease in percentage of immunoglobulin G1 (%lgG1) in breast cancer was analyzed with special emphasis on early tumor stages. IgG1 and total IgG were preoperatively measured in the sera of a total of 801 individuals using a modified quantitative affinity chromatography. Group A consisted of 174 healthy individuals of both sexes, group B of 324 female patients with benign breast disease, and group C of 303 patients with invasive and non-invasive breast cancer. Within group C, 13 patients presented with intraductal carcinoma, and 22 patients with a pT1a-tumour (diameter less than 0.5 cm). The %IgG1 values were compared among groups A, B and C. In addition, correlations were sought between %IgG1 values of group C and tumor size, stage (UICC), histopathological grade and oestrogen (ER) and progesteron receptor (PR) expression. The mean value of %IgG1 in group A was 63.3 +/- 0.5 s.e.m., in group B 57.75 +/- 0.4 s.e.m. and in group C 52.37 +/- 0.5 s.e.m. The differences of mean values were highly significant between all three groups. Sensitivity and specificity of %IgG1 to discriminate between group A and C were 75% and 87%, and between group B and C 62% and 63%, respectively. The significant decrease of %IgG1 in total serum IgG is able to distinguish patients with breast cancer of more than 5 mm in diameter from healthy controls and patients with benign breast diseases. Finally, calculated posterior probabilities revealed that within certain concentration limits %lgG1 may provide predictive information with high probabilities. PMID- 11194456 TI - Alcohol and breast cancer mortality in a cohort study. AB - Available epidemiological evidence indicates that alcohol intake is associated with a higher risk of developing breast cancer. Plausible biological pathways include its effect on levels of estrogens, cell membrane integrity and cell-to cell communication, inhibition of DNA repair, and congener effect. The present study evaluated the impact of alcohol on mortality from breast cancer, an area with relatively few studies in the literature. The subjects were participants in a Canadian prospective cohort study, the National Breast Screening Study (NBSS). Women were enrolled in the cohort from 1980 to 1985 to evaluate the efficacy of mammographic screening. Information on usual diet and alcohol intake at enrolment and other epidemiological variables was collected by means of a mailed, self administered questionnaire. Mortality from breast cancer during follow- up to 31 December, 1993 was ascertained by record linkage to the Canadian Mortality Data Base maintained by Statistics Canada. During the follow-up period of 1980-1993 (average 10.3 years), 223 deaths from breast cancer were identified for this analysis. The hazard ratios for the risk of death from breast cancer increased with intakes of total alcohol of 10-20 g/day (1.039, 1.009-1.071) and > 20 g/day ( 1.063, 1.029-1.098). This increase was contributed largely by the intake of wine, a 15% increase in risk at intakes higher than 10 g/day of alcohol from wine. Alcohol from spirits was associated with a small decrease in risk of death (hazard ratio at 10g/day, 0.945, 0.915-0.976). The effect of alcohol from beer was not significant in the two categories studied. Although our results were statistically significant, the magnitude of the change in risk was small. PMID- 11194457 TI - Inhibition of NF-kappaB activity enhances TRAIL mediated apoptosis in breast cancer cell lines. AB - Most breast cancer cell lines are resistant to TNF-related apoptosis inducing ligand (TRAIL) induced apoptosis. In sensitive breast cancer cell lines TRAIL rapidly induces the cleavage and activation of caspases leading to the subsequent cleavage of downstream caspase substrates. In contrast, there is no caspase activation in the resistant cell lines. The transcription factor NF-KB can inhibit apoptosis induced by a variety of stimuli including activation of death receptors. We investigated whether NF-kappaB contributes to the resistance of breast cancer cells to TRAIL induced apoptosis. All of the resistant breast cancer cell lines expressed NF-kappaB and had detectable NF-kappaB activity in nuclear extracts prior to treatment with TRAIL. Upon TRAIL treatment, a significant increase in NF-kappaB activity was seen in most of the cell lines. To directly test if NF-kappaB activity contributes to the resistance of these cell lines to TRAIL, we transiently transfected the resistant cell lines with an inhibitor of NF-kappaB (IkappaBdeltaN) and measured TRAIL induced apoptosis in control and transfected cells. All of the resistant cell lines tested showed an increase in TRAIL induced apoptosis when transfected with the IKBdeltaN. These results demonstrate that TRAIL resistant breast cancer cells fail to rapidly activate the apoptotic machinery but they do activate NF-kappaB. Inhibition of NF kappaB activity increases the sensitivity to TRAIL mediated apoptosis in resistant cells. These results suggest that agents which inhibit NF-kappaB should increase the clinical efficacy of TRAIL in breast cancer cells. PMID- 11194458 TI - PTP LAR expression compared to prognostic indices in metastatic and non metastatic breast cancer. AB - Several prognostic indices in breast cancer, including c-erbB2, epithelial growth factor receptors (EGFR), estrogen and progesterone receptors are signal transduction molecules. Recently, expression of another signal transduction molecule, the protein tyrosine phosphatase LAR, has been suggested to be increased in breast cancer. The objective of the current investigation was to examine the relationship between LAR expression and prognostic parameters in breast cancer. LAR expression was associated with metastatic potential in the well-characterized 13762NF rat mammary adenocarcinoma clones. The metastatic MTLn3 and MTLn2 clones expressed sizable amounts of LAR. The essentially non metastatic MTC clone had little LAR expression. C-erbB2 had highest expression in the highly metastatic MTLn3 clone, but c-erbB2 levels were sizeable in the weakly metastatic MTLn2 and non-metastatic MTC clone. EGFR expression had the strongest association with a clone's metastatic potential, being very high in MTLn3, weak in MTLn2, and undetectable in MTC. In human breast cancer specimens, LAR expression was strongly positive in 50% of metastatic cases but in only 21% of 'non-metastatic' cases. As with the 13762NF-derived clones, c-erbB2 expression was strongly positive independent of metastatic phenotype. However, 46% (6/13) of cases that were strongly positive for c-erbB2 were strongly positive for LAR. Only 17% (2/11) of negative or weakly c-erbB2 positive samples were strongly positive for LAR. All ER+ positive tumors (n = 15) were positive for LAR and 53% of these tumors were strongly positive for LAR. In ER negative cases, only 1 of 11 was strongly positive for LAR. While the current data indicate a strong association between ER and LAR expression in breast cancer tissue (p = 0.003), additional studies are warranted to further explore the relationship between LAR and prognostic indices of breast cancer progression. PMID- 11194459 TI - Australia maintains its capacity to fight and defeat any outbreak of foot & mouth. PMID- 11194460 TI - Media release hit the right targets. PMID- 11194461 TI - Perth and UK labs combine for PETS. PMID- 11194462 TI - AAHL also involved under PETS scheme. PMID- 11194463 TI - Dysplasia laxity. PMID- 11194464 TI - Caged hens--AVA misses welfare 'boat'. PMID- 11194465 TI - Conservative management of juvenile canine hip dysplasia. PMID- 11194466 TI - Triple pelvic osteotomy for juvenile canine hip dysplasia. PMID- 11194467 TI - Alternative surgical methods for treating juvenile canine hip dysplasia. PMID- 11194468 TI - Effects of an oral vasopressin receptor antagonist (OPC-31260) in a dog with syndrome of inappropriate secretion of antidiuretic hormone. AB - OBJECTIVE: The syndrome of inappropriate secretion of antidiuretic hormone is a rare disorder in dogs characterised by hypo-osmolality and persistent arginine vasopressin production in the absence of hypovolaemia and/or hypotension. The study describes the efficacy and safety of the nonpeptide selective arginine vasopressin V2 receptor antagonist OPC-31260 in a dog with the naturally occurring syndrome. DESIGN: The detailed case history of a dog with spontaneous syndrome of inappropriate secretion of antidiuretic hormone that received long term therapy with oral OPC-31260 is presented. Effects of the first dose of OPC 31260 and of a dose administered after a continuous dosing period of 12 days are reported. PROCEDURE: Packed cell volume, plasma sodium, total protein, arginine vasopressin, renin activity, atrial natriuretic peptide, urine specific gravity, urine output, heart rate and body weight were monitored for 2 h before, and for 4 h after, the first dose of OPC-31260. The same parameters plus plasma osmolality and urine osmolality were monitored when an identical dose was administered after 12 days of therapy. RESULTS: Oral administration of OPC-31260 at 3 mg/kg body weight resulted in marked aquaresis with increased urine output and decline in urine specific gravity within 1 h. Corresponding increases in concentrations of plasma sodium, plasma osmolality and plasma renin activity were recorded over a 4 h period. Arginine vasopressin concentration remained inappropriately elevated throughout the study. Results were similar when the trial procedure was repeated after a stabilisation period of 12 days. Long-term therapy with OPC-31260 at a dose of 3 mg/kg body weight orally every 12 h resulted in good control of clinical signs with no deleterious effects detected during a 3-year follow-up period. Despite sustained clinical benefits observed in this case, plasma sodium did not normalise with continued administration of the drug. CONCLUSIONS: Treatment of a dog with naturally occurring syndrome of inappropriate secretion of antidiuretic hormone with OPC-31260 at 3 mg/kg body weight orally every 12 h resulted in marked aquaresis and significant palliation of clinical signs with no discernible side-effects detected over a 3-year period. Thus, OPC-31260 appears to offer a feasible medical alternative to water restriction for treatment of dogs with syndrome of inappropriate secretion of antidiuretic hormone. Higher doses of OPC-31260 may be required to achieve and maintain normal plasma sodium in dogs with this syndrome. PMID- 11194469 TI - Evaluation of an insulin zinc suspension for control of naturally occurring diabetes mellitus in dogs. AB - OBJECTIVE: To evaluate duration of action of an insulin zinc suspension (Caninsulin, Intervet) in spontaneously occurring cases of canine diabetes mellitus and suitability of its use as a once daily administered insulin for treatment of this disease. DESIGN: Eight client-owned canine diabetics were included in a prospective pilot study. All dogs had been treated with Caninsulin for a minimum of 2 months and were considered on clinical grounds to be adequately stabilised. PROCEDURE: Dogs were hospitalised for 24 h and blood collected every 2 h via indwelling venous catheters for blood glucose determination. RESULTS: Once daily Caninsulin administration failed to maintain glycaemic control for greater than 13 h in five of eight dogs, but acceptable blood glucose concentrations were maintained for 22 h and greater than 24 h in two others. One dog became distressed during hospitalisation and the blood glucose curve did not show an identifiable response to the insulin. CONCLUSION: Most diabetic dogs may require twice daily administration of Caninsulin for satisfactory glycaemic control, but once daily administration may be adequate in some animals. More comprehensive investigation into duration of activity of Caninsulin is warranted. PMID- 11194470 TI - In vitro antimicrobial susceptibilities of three Porphyromonas spp and responses in the oral cavity of cats to treatment with selected antimicrobial drugs. PMID- 11194471 TI - The BSE inquiry and communication of risk. PMID- 11194472 TI - Effects of tail amputation and treatment with an albendazole controlled-release capsule on the health and productivity of prime lambs. AB - OBJECTIVE: To assess the effects of tail amputation and treatment with albendazole controlled-release capsule (CRC) on the health and productivity of prime lambs. DESIGN: Field trials on three farms. ANIMALS: About 551 Coopworth Poll Dorset cross, 588 Border Leicester-Merino-Poll Dorset cross and 575 Corriedale-Poll Dorset cross lambs. PROCEDURE: On three farms, lambs with amputated tails were compared with an equal number of lambs with tails left entire. In both of these groups half the lambs were treated with an albendazole CRC 13 weeks after the start of lambing. Faecal soiling of the breech and flystrike of the breech were recorded. Lambs were weighed and body condition scored at each visit and carcase weights and fat score of each lamb at slaughter. Procedures on the slaughter chain were monitored to determine whether the retention of the tail caused any problems. RESULTS: There were no observed benefits of treatment with an albendazole CRC on the farms in the study. There was no strong evidence that tail amputation had any long-term effect on the growth rate of lambs or carcase traits. No detrimental effects were observed during processing of lambs with long tails in the abattoir. Lambs with entire tails had significantly greater mean dag scores than lambs with amputated tails. On one farm lambs with entire tails were at about twice the risk of requiring crutching and on another farm were at three times the risk of breech strike compared with lambs with amputated tails. CONCLUSION: This study provides evidence that amputating the tail is not an absolute requirement to maintain the health and welfare of prime lambs, but leaving the tail of prime lambs entire is likely to increase chemical usage to control flystrike, and to increase the frequency of crutching. PMID- 11194473 TI - Surveys in Papua New Guinea to detect the presence of Trypanosoma evansi infection. AB - OBJECTIVE: To confirm serological evidence that Trypanosoma evansi is present in Papua New Guinea. DESIGN: Three surveys were undertaken in PNG during 1997/1998. Animals were selected for sampling on the basis of convenience. Samples of blood were examined for the presence of T evansi by the haematocrit centrifugation technique (HCT) and mouse inoculation test (MI). Sera were tested in the field using the card agglutination test for trypanosomiasis/T evansi (CATT). Bovine sera were tested at James Cook University using an antibody-detection ELISA (Ab ELISA). Results from testing bovine sera with the Ab-ELISA and sera from wallabies with the CATT were analysed using FreeCalc to determine the probability that animals in these populations were infected with T evansi. RESULTS: A total of 545 serum samples were collected, during the three surveys of which 39 cattle, two pig and three agile wallaby samples were positive with the CATT. All bovine sera collected were negative when tested with an Ab-ELISA. T evansi was not isolated using the HCT or the MI from any of these animals. CONCLUSION: Based on the Ab-ELISA results it was concluded that T evansi infection was not present in cattle in villages around Balimo at a minimum expected prevalence of 10% (P < 0.05) and, based on the CATT results, that infection was not present in wallabies on the Bula plain at a minimum expected prevalence of 10% (P < 0.1). These results indicate that it is unlikely that T evansi is endemic in PNG. PMID- 11194474 TI - Application of ERIC-PCR for the comparison of isolates of Haemophilus parasuis. AB - OBJECTIVE: To validate a polymerase chain reaction (PCR) based method. Enterobacterial Repetitive Intergenic Consensus-PCR (ERIC-PCR), for the fingerprinting of Haemophilus parasuis strains and to use that method to differentiate isolates from apparently related outbreaks of Glasser's disease on three pig farms. DESIGN: ERIC-PCR was evaluated by comparing 15 different strains that represented all 15 recognised serovars in the Kielstein-Rapp-Gabrielson (KRG) scheme for serotyping H parasuis. Next, ERIC-PCR was used to examine 14 Australian field isolates of H parasuis; 12 collected from three farms suffering apparently related outbreaks of Glasser's disease and two from two other farms with no known connection. RESULTS: The 15 serovar reference strains all gave unique, reproducible ERIC-PCR fingerprints. The 12 isolates from the three apparently related outbreaks all gave a single fingerprint, which was distinct from any seen in the 15 serovar reference strains and the two other Australian field isolates in the studied farms. The confirmation that all 12 isolates were the same strain allowed the development of a prevention and control program that has prevented the emergence of any further outbreaks of Glasser's disease on the three farms. CONCLUSION: ERIC-PCR is a suitable technique for the differentiation of unrelated strains of H parasuis. The finding that the 12 field isolates of H parasuis all shared the same fingerprint is strong evidence that there was a common source of infection on all three farms. This study has shown, for the first time, that ERIC-PCR is a suitable technique for the sub-typing of H parasuis and useful for studying the epidemiology of outbreaks of Glasser's disease. PMID- 11194475 TI - Sensitivity and specificity of two serological tests for the detection of ovine paratuberculosis. AB - OBJECTIVE: To determine the sensitivity and specificity of an absorbed ELISA and an AGID test for the detection of clinical and subclinical paratuberculosis in sheep. DESIGN: By testing a panel of sera from 1257 Australian Merino and crossbred sheep greater than 1 year of age, of which 1137 sheep were not infected with Mycobacterium avium subsp paratuberculosis and 120 sheep had paratuberculosis. PROCEDURE: Sera were collected from 457 sheep in Victoria and 800 sheep in Western Australia. Presence of M a paratuberculosis infection in Victorian sheep was determined by histological examination of intestinal tissues, whereas sheep from Western Australia were presumed to be free of Johne's disease. The ability of an absorbed ELISA to discriminate between infected and uninfected sheep was described by test sensitivity and specificity, the distribution of ELISA OD, and the area under a receiver operating characteristic curve. RESULTS: The absorbed ELISA had a specificity of 98.2 to 99.5% (CI) and a sensitivity of 35 to 54% (CI). In sheep from infected flocks in Victoria, the AGID test had a specificity of 99 to 100% (CI) and a sensitivity of 38 to 56% (CI). The sensitivity of serological tests was higher in sheep with a body condition representative of the lower quintile of their flock of origin. CONCLUSION: The AGID test and absorbed ELISA are useful tests for the detection of ovine paratuberculosis. Although the tests had a similar accuracy, they detected different subpopulations of infected sheep with only moderate overlap. The AGID test had a higher specificity than the absorbed ELISA. PMID- 11194476 TI - Effect of ephemeral fever of cattle on the appearance and contraction of blood clots. PMID- 11194477 TI - Pyogranulomatous enteritis in sheep due to penetrating seed heads of Dittrichia graveolens. PMID- 11194478 TI - [Report of the hospital discharge of the patient with myocardial infarct]. PMID- 11194479 TI - [Opioids. Pharmacology, clinic, prospectives for an extensive use]. PMID- 11194480 TI - [Deciding in conditions of uncertainty: the Delphi method and its use in the formulation of guidelines]. AB - The purpose of this paper is to analyze one of the most powerful tools in the decision-making under conditions of uncertainty, the Delphi method, and to verify the related interest of scientific world, particularly, for formulation of guidelines. The method combines the expert opinion preventing biases due to institutional role, status or dominant personality. In the text we explain the methodology and the steps through which it is possible to realize the consensus; we schematized in a didactic manner all the phases for an operational approach of the reader. The search by the most diffused biomedical database (Medline) individualized 623 citations, 7 of which are guidelines (3 of remarkable importance). In conclusion, the Delphi method may be considered particularly interesting for its theoretical assumptions and it can be used as reference tool for assuming decisions in the formulation of clinical practice guidelines as objectively as possible. PMID- 11194481 TI - [Hyperthyroidism, therapy with erythropoietin, malnutrition and systolic function in hemodialysis: echocardiography study]. AB - Secondary hyperparathyroidism is a frequent condition of dialysis patients. Endocrine derangements, with disturbance of calcium metabolism are complex, involving bone, heart (left ventricular hypertrophy-dilatation), bone marrow (anemia and erythropoietin resistance), muscle (increase of body fat mass) and insulin resistance. Aim of the study was to assess how these conditions are inter correlated in the same patients. 45 patients (m 20, f 25; years 61.8 +/- 11.6) in maintenance bicarbonate three-weekly hemodialysis since > 3 years were studied. Cardiac function was assessed by echocardiography (EF%: left ventricular ejection fraction), which showed an inverse correlation both with parathormone (iPTH vs EF%: r = -0.64; p < 0.001) and with erythropoietin (rHu-EPO vs EF%: r = -0.62; p < 0.001). This suggests the possibility of a multi-endocrine resistance in dialysis patients with chronic renal failure, secondary to the degree of malnutrition. Lower lean mass is correlated with hyperparathyroidism (iPTH vs fat mass%: r = 0.37; p < 0.01), with lower left ventricular systolic function (EF% vs fat mass%: r = -0.41; p < 0.005) and with rHu-EPO resistance. Moreover, patients with higher iPTH show a hypercatabolic disposition, assessed as protein catabolic rate (PCR/kg vs iPTH r = 0.54; p < 0.001). This pattern can be a consequence of chronic renal failure, but bio-compatibility of materials can be involved as well. PMID- 11194483 TI - [Intraparenchymal mycotic tonsillitis in childhood]. PMID- 11194482 TI - [Pituitary pathology in elderly patients admitted in a division of internal medicine. Description of 3 cases]. AB - Pituitary diseases are often unrecognized in the elderly, although if they can be at the basis of several pathological conditions. We report three clinical cases. Patient n. 1: 87 years old woman, in poor general condition. Thyroid function evaluation showed secondary hypothyroidism. Subsequent pituitary function evaluation demonstrated hypopituitarism with empty sella. The diagnosis was "hypopituitarism with secondary hypothyroidism and adrenocortical insufficiency, in empty sella" starting substitutive treatment with glucocorticoids and L thyroxine, with improvement in her clinical conditions. Patient n. 2: 74 years old woman, with severe congestive heart failure. Her clinical history revealed hypothyroidism. An endocrine evaluation (in absence of therapy) demonstrated panhypopituitarism with secondary hypothyroidism and adrenocortical insufficiency in presence of empty sella. The patients was started on substitutive treatment and her conditions improved. Patient n. 3: 74 years old man with several atrial fibrillation episodes and hyperthyroidism. Thyroid function evaluation suggested secondary hyperthyroidism confirmed by the presence of a pituitary macroadenoma. The patient underwent surgical adenomectomy by trans-sphenoidal route. The clinical conditions of the patient improved, but a slight secondary hyperthyroidism was still present caused by the persistence of residual pathological tissue in the right cavernous sinus region confirmed by octreoscan suggesting the presence of a lesion endowed with somatostatin receptors. The patient was started on long acting octreotide treatment, which is still in progress. In conclusion, pituitary diseases pass often unrecognized in the elderly. Their prompt recognition and treatment can resolve dangerous situations for the patients. PMID- 11194484 TI - [Genetic basis of sudden cardiac death]. PMID- 11194485 TI - [High-dose chemotherapy in carcinoma of the breast. Sunshine and shadows]. PMID- 11194486 TI - [The obesity problem, today]. PMID- 11194487 TI - [Influenza]. AB - Influenza outbreaks remain today among the most serious and intractable health problems owing to high rates of morbidity and high economic costs. Periodical epidemics and pandemics in temperate regions of the world are due to high genetic variability of influenza viruses, which concerns primarily haemagglutinin and neuraminidase antigens (antigenic drift and shift). Most influenza infections are self-limited, but they cause increased mortality in high-risk groups of population (such as the elderly and the subjects with chronic diseases) and increased morbidity in the general population, with loss of productivity and high health costs. During the past thirty years, efforts to control influenza have focused on the use of inactivated vaccines in high-risk groups and of two antiviral drugs, amantadine and rimantadine. However, the wide spread of influenza in all population groups and the limits of adamantane compounds induced to investigate novel approaches for prevention and control of flu. The new live attenuated, cold-adapted, trivalent intranasal vaccine was shown to be highly effective in children against influenza A (H3N2) and B viruses. The new antiviral drugs (zanamivir and oseltamivir), neuraminidase inhibitors, reduced the median time to alleviation of the major symptoms of influenza by 1-2 days. These advances in the last few years will certainly modify our approaches to influenza treatment and prevention. PMID- 11194488 TI - [Rhino-bronchial syndrome]. AB - A close anatomical and functional relationship between superior and inferior airways is well documented. A typical example is offered by the close relationship between allergic rhinitis and asthma whose close connection is documented by epidemiological and pathological data. The mechanisms which can explain this phenomenon are not fully known but naso-bronchial reflexes, mouth breathing due to nasal obstruction and aspiration of nasal secretions seem all to be important. Moreover it has been recently proved that the treatment of rhinitis can improve the concomitant asthma thus confirming their relationship. Another less frequent association is between sinusitis and asthma. Such a connection seems to be frequent in patients suffering of atopic rhinitis but also in patients presenting a nasal obstruction of different nature such as deviations of the nasal septum, adenoid hypertrophy etc. Also in this case a correct medical or surgical treatment of sinusitis can improve asthma symptomathology. Finally a classic example of involvement of superior and inferior airways is represented by the syndrome of ASA intolerance. These patients in fact initially complain of rhinitis which afterwards is complicated by the onset of nasal polyposis and asthma which can prove clinically very severe. Nowadays, anyway, there is no evidence that the treatment of rhinitis or polypectomy can improve the clinical course of asthma. In conclusion, diseases of superior and inferior airways must be considered in strict connection and need the same global treatment. PMID- 11194489 TI - [Reye's syndrome: the death of a syndrome? (Or death by a syndrome?)]. AB - Reye syndrome is characterized by acute encephalopathy and fatty degeneration of the liver almost exclusively in children. The onset is heralded by profuse vomiting and varying neurologic impairment from irritability to coma, decerebration and death. The encephalopathy must be associated with a greater increase in the levels of ammonia, or alanine amino-transferase and aspartate amino-transferase in serum; and with a fatty metamorphosis of the liver diagnosed by biopsy or at autopsy. The only characteristic universally accepted as diagnostic are the specific mithocondrial changes in the liver-biopsy specimen. Larger studies confirmed the association of aspirin with RS. The CDC of Atlanta cautioned physician and parents and a dramatic decline in case began at that time. Classic Reye syndrome is now so rare in the USA that when an apparent case is encountered in a child who has not taken aspirin, other diagnoses should be considered. After a brief survey of RS relative lack of specificity of case definition and of the polyhedric etiopathogenetic moments, the A. on the personal experience, point: a) the biological unicity of the man and the necessary coexistence of "constitutional" factors (metabolic and/or endocrine, and/or immunitary factors, the later almost never investigated), toxic, and infectious factors for the syndrome's deflagration; b) some aspects of the continued existence of therapeutic and diagnostic problems: the aspirin and/or salicilate use and the pharmacogenetic; the continued existence of other, generally similar conditions, such the drug and other known and unknown toxic mithocondrial factors that provoke this unusual response to common infections; and the inborn errors of metabolism; c) some practical aspects of diagnostic and therapeutic approach. PMID- 11194490 TI - [The use of erythropoietin alpha in programs of high-dose chemotherapy]. AB - Epoetin (Epo) is physiologically present in the human body, stimulating erythropoiesis from bone marrow. Anemia is observed in cancer patients submitted to high-dose chemotherapy (HDCT), mainly caused by myelosuppression. Epoetin alfa has been widely used to treat the anemia that develops in the HDCT setting. Controlled studies in patients with hematologic malignancies or solid tumors who received Epo following HDCT have shown a decreased red blood cell transfusion requirement at least in patients receiving allogeneic bone marrow transplantation (BMT), while results in patients receiving autologous BMT have been disappointing. The administration of Epo before HDCT, in a period when bone marrow is still responsive to growth factors, may represent a new strategy aimed at decreasing the degree of anemia in these patients. A combination of granulocyte-colony stimulating factor and Epo has proved to be effective in mobilizing stem cell and committed myeloid/erythroid precursors. PMID- 11194492 TI - [Psychiatry of women: an new field of research in mental health]. AB - This paper presents the state of the art of our current knowledge in the field of female psychiatry. This domain of mental health studies the particularities of psychological distress in women. It is a new concept, and its creation is subtended by some clinical and epidemiological realities. The creation of this very interesting field of research has been promoted on the one hand because of the existence of certain female-specific psychiatric disorders (premenstrual syndrome, post-partum psychopathologies, pseudocyesis, Ferjol's syndrome and menopause-related disorders) and on the other hand because the vast majority of mental diseases may be expressing major gender-related variations (prevalence, natural history of disease, symptomatology, prognosis and treatment outcome). Research in female psychiatry has numerous goals. First of all, the sex-based differences in the prevalence of mental disorders (e.g., depression, schizophrenia, anxiety, anorexia nervosa, personality disorders) has to be understood (are they artefacts, or the expression of hormonal or genetic influence, or a consequence of social factors, or even the result of brain development?). Second, the specific nature of some of these diseases is under investigation (e.g., is postnatal depression a classical major depressive disorder or a puerperal-specific disease?). And third, treatments must be adapted accordingly. Indeed, the study of female psychiatry attempts the integration of the gender-effect in order to improve the treatment modalities. PMID- 11194491 TI - [The importance of syndrome X in daily practice]. AB - Metabolic syndrome X includes glucose intolerance or type 2 diabetes, dyslipidemia and arterial hypertension which are classical cardiovascular (CV) risk factors. In course of time, other CV risk factors have been added to the syndrome: rheological alterations, endothelial dysfunction, anomalies in the coagulation/fibrinolysis system, microalbuminuria and so on.... Insulin resistance is the cornerstone of metabolic syndrome X, with secondary hyperinsulinism. Upper body obesity is associated with metabolic syndrome X. Simple waist measurements can detect the subjects (10-15% of the population) at increased CV risk with a sensitivity of 70%. This is invaluable for such a simple and cheap test. Diet is the first step in treating these patients and reducing caloric intake is necessary in most of them. Saturated fats will be replaced by polyunsaturated and mono-unsaturated ones. Long-chain carbohydrates with low glycemic index will be suggested. Regular physical activity will be promoted. If these life style modifications fail, drugs can be added: biguanide and glitazone are good candidates. Orlistat has improved metabolic syndrome X on a long-term basis. Drugs that could increase insulin resistance are to be avoided. PMID- 11194493 TI - [Why radiation for the postmastectomy patient?]. AB - We can identify a subgroup of patients with a high risk of loco-regional relapse after mastectomy. When those patients are irradiated, their absolute loco regional relapse risk drops for more than 10% with a relative risk reduction of 66% (p < 0.0001). The severe complication rate is below 1%. With earlier radiotherapy techniques, there was an excess in long term cardiac mortality among irradiated patients. Even if the breast specific survival was improved with radiotherapy, the overall survival was not better. Three recent randomised trials have shown that postmastectomy radiotherapy adds 10% survival benefit to an adjuvant systemic treatment. The impact of radiotherapy on overall survival is more pronounced for less advanced tumors. PMID- 11194494 TI - [Reduction of perinatal transmission of HIV-1: antiretroviral prophylaxis and obstetrical interventions]. AB - Incorporation of zidovudine prophylaxis (given to the mother during the third trimester of pregnancy and at delivery and to the newborn during the first 6 weeks of life) in clinical practice has substantially reduced the perinatal transmission of HIV-1 and the number of pediatric AIDS cases in industrialized countries. Rates of transmission of +/- 1% have been observed with the combination of antiretroviral prophylaxis and elective caesarean delivery. Elimination of perinatal transmission of HIV is therefore a feasible goal in Europe and the United States. Recent studies have identified less complex and less expensive preventive therapies more applicable to developing countries. PMID- 11194495 TI - [Dopaminergic agonists in the treatment of Parkinson's disease]. AB - After levodopa, dopaminergic agonists are the most powerful agents in idiopathic Parkinson's disease treatment. Used in monotherapy or rather in early combination with levodopa, they allow a dramatic reduction of long-term motor side effects of the latter: onset and peak-dose dyskinesias, early morning dystonias. Their gastro-intestinal (nauseas) and moreover psychiatric (confusion and hallucinations) side effects limit their use, notably in geriatric populations. Superiority of so-called "second generation" agonists (ropinirole, pramipexole) on "first generation" agonists (bromocriptine, pergolide) remains to be proved. PMID- 11194496 TI - [Medical teaching skills and basic science]. PMID- 11194497 TI - [The quota system in Europe: its place in Belgium]. PMID- 11194498 TI - [The quota system and its financial impact on the Erasmus Hospital]. PMID- 11194499 TI - [Treatment of iatrogenic ureteral injuries]. PMID- 11194500 TI - [A new method of scintigraphy]. PMID- 11194501 TI - [Therapy of chronic inflammatory intestinal disease]. PMID- 11194502 TI - [Colorectal cancer: importance of early diagnosis]. PMID- 11194503 TI - [Differential diagnosis in hyperferritinemia]. PMID- 11194504 TI - [7th Conference on Retroviruses and Opportunistic Infections]. PMID- 11194505 TI - [Erasmus and medicine]. PMID- 11194506 TI - [Workshop: immunosuppression in chickens]. PMID- 11194507 TI - [Immunocastration is one step further in the castration of pigs]. PMID- 11194508 TI - [Practical remarks in response to the question and answer about artificial insemination of the dog]. PMID- 11194509 TI - [The importance of different pig diseases in the Netherlands]. AB - As part of the project 'Clean pigs', IPG Institute for Pig Genetics BV made an inventory of the impact of different diseases on the Dutch pig industry. An expert panel assessed the importance of the different diseases with regard to public health, farm economy, the pig sector and export sales. The possibilities for the diagnosis of the different pathogens were listed and the goal for the next years, was set. Diseases were classified into three categories, according to their importance for the Dutch pig industry (Table 2). The diseases that can be eradicated are Salmonella (only specific strains), Pasteurella multocida DNT + PAR), Actinobacillus pleuropneumoniae, Haematopinus suis (lice) and Sarcoptes scabei (var. suis) (mange). National introduction of list A en most list B diseases of the OIE classification must be prevented. PMID- 11194511 TI - [KNMvD: banning some dog breeds will not solve the aggression problem]. PMID- 11194512 TI - [The recognition rule in the practice]. PMID- 11194513 TI - [Molecular effects and neuronal nets]. PMID- 11194514 TI - [Neural mechanisms of anesthesia]. AB - Positron emission tomography studies on volunteers showed that, at concentrations inducing the loss of consciousness, propofol, halothane and isoflurane reduce glucose metabolism of neocortical neurones by 20-50%. To find out whether these effects are caused by direct anaesthetic actions on cortical structures, experiments were carried out on isolated neocortical brain slices. In these investigations an excellent correlation was observed between anaesthetic concentrations causing a half-maximal depression of action potential firing in neocortical brain slices and anaesthetic blood concentrations monitored during awaking from anaesthesia in humans. Furthermore, it could be shown that, at concentrations approximately one half the MAC-value, isoflurane decreases the frequency of auditory evoked 30-40 Hz oscillations in the neocortex by 50%. Similar quantitative effects were observed on spontaneously occurring high frequency rhythms in neocortical brain slices. However, not all aspects of cerebral anaesthetic actions can be explained by direct effects on cortical neurones. The EEG synchronisation and the amplitude reduction of mid latency auditory evoked potentials are probably related to the inhibition of thalamic neurones. Halothane, isoflurane, enflurane and propofol reduced action potential firing of cortical neurones by enhancing GABAA receptor-mediated synaptic inhibition. This molecular mechanism seems also to be involved in depressing painful stimuli-induced motor responses. Nevertheless, there must be a difference between relevant anaesthetic mechanisms on the cerebral and spinal level. This follows from the observation that the relation between the concentration causing the loss of consciousness and the concentration that depresses movements considerably varies among different anaesthetic agents. PMID- 11194515 TI - [Invasive Candida infection in surgical patients: a valid clinical entity]. AB - OBJECTIVE: Establishment of a case definition for invasive candidosis in postsurgical intensive care patients. METHODS: During the period of 1996-1999, 8 cases of invasive candidosis were observed on a surgical intensive care unit. Patient records were evaluated with respect to diagnostic criteria and response to antimycotic therapy. RESULTS: Patients included 3 women and 5 men with a mean age of 62.7 (37-85) years. Candida peritonitis (n = 6) occurred after surgery or perforation of the intestinal tract, and Candida pneumonia was due to artificial ventilation (n = 3). C. albicans was isolated in all 8 cases, but mixed infections with other Candida spp. occurred in 3 cases. The Candida serum antigen test yielded a positive result in only 2/8 cases. I.v. therapy with fluconazole was successful in 7 cases, one patient with severe initial disease died with ongoing infection. With the exception of the lethal case, all patients showed a diagnostic serum antibody test, proving systemic candida infection. CONCLUSION: Based on the case descriptions, we propose the following definition of invasive candidosis: (1) Clinical signs of infection after surgery, (2) absence of bacterial pathogens and/or failure to respond to systemic antibiotics, (3) cultivation of Candida spp. from normally sterile sites or abundant growth in tracheal aspirate, (4) response to antimycotic therapy and (5) diagnostic serum antibody test. This definition proved to be valid for our patients and could be used as an inclusion criterion for future clinical studies of serodiagnosis of Candida infection or antimycotic chemotherapy. PMID- 11194516 TI - [Comparison of hydroxyethyl starch solutions derived from potato and corn starch] . AB - OBJECTIVE: The study was designed to investigate the effects of hydroxyethyl starch (HES) solutions derived from potato (p) compared to HES derived from corn (c) starch on the colloidosmotic pressure, plasma viscosity, and to measure the plasma and urine concentration. METHODS: After approval by the Ethics Committee, and having obtained informed consent, we recruited 20 patients undergoing lumbar disc surgery who received either 1000 ml of p-HES or c-HES (MW 200,000 DS 0.5) in a randomized, single-blind way. Colloidosmotic pressure, plasma viscosity and the plasma concentration were measured before and 30, 90, 240 min and one day after the infusion. Statistical analysis was performed using chi-square and Mann Whitney test. There were no differences between the two groups in regard to demographics and anesthesia. RESULTS: Plasma viscosity and colloidosmotic pressure did not change significantly during that time. There were no differences in plasma concentration and excretion of both solutions. The peak plasma concentration was reached after 30 min in both groups (8.57 +/- 3.92 g/l c-group and 7.67 +/- 4.68 g/l p-group) and declined thereafter. Within 6 h 38% (c-group 23.0 +/- 3.2 g HES) and 28% (p-group 16.8 +/- 1.6 g HES) of the infused HES were found in the urine. 12 h later about 50% was excreted. CONCLUSION: The present study demonstrated that there was no clinically apparent effect on hematorheology and pharmacokinetics between these two solutions. PMID- 11194517 TI - [Value of reflecting disposable insulation (Thermodrape) in preventing perioperative hypothermia]. AB - OBJECTIVE: The aim of the study was to evaluate the value of reflecting disposable insulation for the prevention of perioperative hypothermia. METHODS: After approval by the local ethics committee 36 patients undergoing long lasting urological intraabdominal surgery were studied. Anaesthesia was performed using etomidate, fentanyl, midazolam, pancuronium and succinylcholine. Patients were randomly assigned to 4 groups. These groups were treated as follows: Gr. 1: Infusion warmer (Hotline HL-90 with System L-70, Level 1 Technologies Inc., Marshfield, USA) and standard O.R. draping with two layers of cotton drapes. Gr. 2: Infusion warmer and reflecting disposable insulation (Thermadrape, O.R. Concepts Inc., Roanoke, USA) covering the legs, upper body, arms and head. Gr. 3: Infusion warmer and convective air warming with upper body blanket (WarmTouch, Mallinckrodt Medical, Hennef/Sieg, Germany). Gr. 4: Infusion warmer, convective air warming and reflecting disposable insulation. RESULTS: After 2 hours of surgery patients of groups 1 and 2 became hypothermic with core temperatures of 35.1 and 35.6 degrees C respectively. No relevant difference could be found between the two groups. The combination of an infusion warmer and convective air warming was an effective method to prevent hypothermia in groups 3 and 4. After 2 hours of surgery these patients had core temperatures of 36.6 and 36.4 degrees C respectively. Reflecting disposable insulation did not improve the effect of convective air warming. CONCLUSION: Reflecting disposable insulation was insufficient in the investigated operative setting. PMID- 11194518 TI - [Autologous phasmapheresis--from euphoria to rationality: practical handling of scientific knowledge. Part 3. Autologous plasmapheresis: valuable coagulation treatment or expansive volume replacement? Physiology and pharmacology]. PMID- 11194519 TI - [Autologous plasmapheresis: ingenious coagulation treatment or expensive volume replacement?]. PMID- 11194520 TI - [Hemoglobin solutions]. PMID- 11194521 TI - [Autologous blood transfusion form the anesthesiologist's viewpoint]. PMID- 11194522 TI - [Perspectives on autologous transfusion from the transfusion physician's viewpoint]. PMID- 11194523 TI - Airway rescue with the intubating laryngeal mask in a patient with an unexpectedly large epiglottic cyst. AB - We report the successful use of the intubating laryngeal mask airway for rescue and intubation in an anaesthetised patient with an unexpectedly large epiglottic cyst. This case illustrates that airway rescue and intubation with the intubating laryngeal mask is possible and preoperative airway assessment does not always provide reliable information about airway management. PMID- 11194524 TI - [Perioperative treatment of a patient with hereditary angioedema (HAE) in a case of a young patient with osteosynthesis from a femoral fracture]. AB - The following case report describes hereditary angioedema (HAE) in a juvenile male patient presenting with femoral fracture. The clinical characteristics, pathophysiological changes, diagnostics and management of anaesthesia for patients with hereditary angioedema will be discussed. Hereditary angioedema (HAE) is a rare autosomal dominant disorder, which is caused by congenital deficiency of functional C1-inhibitor (C1-INH). Patients are suffering from episodic and painless edema of the skin (face and limbs) and mucous membranes of the respiratory and gastrointestinal tracts (the latter causing abdominal cramps due to edema of the intestine). Life-threatening airway obstruction may occur when patients develop laryngeal edema. It is important to differentiate HAE from the more frequent allergic angioedema because of differences in the pharmacological treatment of acute attacks of HAE. C1-INH-concentrate is effective in both treatment of acute attacks and prevention of edema, especially in children, juveniles and young women. PMID- 11194525 TI - Nutrition in bone health revisited: a story beyond calcium. AB - Osteoporosis is a complex, multi-factorial condition characterized by reduced bone mass and impaired micro-architectural structure, leading to an increased susceptibility to fractures. Although most of the bone strength (including bone mass and quality) is genetically determined, many other factors (nutritional, environmental and life-style) also influence bone. Nutrition is important modifiable factor in the development and maintenance of bone mass and the prevention and treatment of osteoporosis. Approximately 80-90% of bone mineral content is comprised of calcium and phosphorus. Other dietary components, such as protein, magnesium, zinc, copper, iron, fluoride, vitamins D, A, C, and K are required for normal bone metabolism, while other ingested compounds not usually categorized as nutrients (e.g. caffeine, alcohol, phytoestrogens) may also impact bone health. Unraveling the interaction between different factors; nutritional, environmental, life style, and heredity help us to understand the complexity of the development of osteoporosis and subsequent fractures. This paper reviews the role of dietary components on bone health throughout different stages of life. Each nutrient is discussed separately, however the fact that many nutrients are co-dependent and simultaneously interact with genetic and environmental factors should not be neglected. The complexity of the interactions is probably the reason why there are controversial or inconsistent findings regarding the contribution of a single or a group of nutrients in bone health. PMID- 11194526 TI - American ginseng improves glycemia in individuals with normal glucose tolerance: effect of dose and time escalation. AB - OBJECTIVE: We studied the effect of escalating the dose and administration time of American ginseng (AG, Panax quinquefolius L.) in nondiabetic individuals to achieve further improvements in glucose tolerance seen previously when 3 g of AG was taken 40 minutes before a 25 g glucose challenge. METHODS: Ten nondiabetic individuals (6M:4F; mean +/- STD: age = 41 +/- 13 years, BMI = 24.8 +/- 3.5 kg/m2, FBG = 4.5 +/- 0.1 mmol L(-1)) on 12 separate occasions, randomly received 0 (placebo), 3, 6 or 9 g of ground AG root at 40, 80, or 120 minutes before a 25 g oral glucose challenge. Capillary blood glucose was measured prior to ingestion of AG or placebo capsules and at 0, 15, 30, 45, 60 and 90 minutes from start of challenge. RESULTS: Compared with the placebo, 3, 6 and 9 g of AG reduced (p<0.05) postprandial incremental glucose at 30, 45 and 60 minutes; also, 3 and 9 g of AG did so at 90 minutes. At 60 minutes, 9 g of AG reduced incremental postprandial glucose relative to 3 g of AG (p<0.05). All AG doses reduced (p<0.05) area under the incremental glucose curve (3 g, 26.6%; 6 g, 29.3%; 9 g, 38.5%). AG taken at different times did not have an additional influence on postprandial glycemia. CONCLUSIONS: In nondiabetic individuals, 3, 6 or 9 g of AG taken 40, 80 or 120 minutes before a glucose challenge similarly improved glucose tolerance. PMID- 11194527 TI - Responses of plasma lipoproteins and sex hormones to the consumption of lean fish incorporated in a prudent-type diet in normolipidemic men. AB - OBJECTIVE: The effects of lean fish on plasma lipoproteins, postheparin plasma lipolytic activities and sex hormones were examined in 11 normolipidemic male subjects. METHODS: This study was a randomized crossover trial of two isoenergetic prudent-type diets, lean fish diet and beef, pork, veal, eggs and milk (nonfish) diet. Experimental diets provided approximately 11800 kJ--18% as proteins, 50% as carbohydrates, 32% as lipids [ratio of polyunsaturated to saturated fatty acids (P:S) of 1:1 compared with 0.5:1 in preexperimental diet], and 260 mg cholesterol/day. RESULTS: Compared with the nonfish diet, the lean fish diet induced higher plasma total and LDL apolipoprotein (apo) B and apo B:apo A-1 ratio, indicating that the substitution of lean fish for beef, veal, pork, eggs and milk provides little benefits with regard to plasma apo B concentrations in a low-fat high P:S diet. Moreover, triglycerides:apo B and cholesterol:apo B ratios of VLDL were lower following the lean fish diet than the nonfish diet, suggesting the presence of smaller very low-density lipoprotein (VLDL) particles following the consumption of lean fish. Higher plasma concentrations of sex hormone-binding globulin (SHBG), HDL2 cholesterol and HDL2:HDL3 cholesterol ratio were found with the lean fish diet compared with the nonfish diet. Negative correlations between plasma postheparin lipoprotein lipase (LPL) activity and VLDL triglycerides (n = 11, r = -0.53, p = 0.02), and between plasma postheparin LPL activity and VLDL triglycerides:apo B ratio (n = 11, r = 0.64, p = 0.02) were also observed following the lean fish diet. CONCLUSION: These results suggest that the effects of substituting lean fish for beef, veal, pork, eggs and milk on plasma lipoproteins may be partly associated with variations in plasma sex hormone status and plasma LPL activity in normolipidemic men. PMID- 11194528 TI - Dairy calcium is related to changes in body composition during a two-year exercise intervention in young women. AB - OBJECTIVE: Relationships between micronutrients and dairy product intake and changes in body weight and composition over two years were investigated. DESIGN: Two year prospective non-concurrent analysis of the effect of calcium intake on changes in body composition during a two year exercise intervention. SUBJECTS: 54 normal weight young women, 18 to 31 years of age. MEASURES OF OUTCOME: Mean intakes of nutrients of interest were determined from three-day diet records completed at baseline and every six months for two years. The change in total body weight and body composition (assessed by dual x-ray absorptiometry) from baseline to two years was also determined. RESULTS: Total calcium/kilocalories and vitamin A together predicted (negatively and positively, respectively) changes in body weight (R2 = 0.19) and body fat (R2 = 0.27). Further, there was an interaction of calcium and energy intake in predicting changes in body weight, such that, only at lower energy intakes, calcium intake (not adjusted for energy) predicted changes in body weight. CONCLUSIONS: Regardless of exercise group assignment, calcium adjusted for energy intake had a negative relationship and vitamin A intake a positive relationship with two year changes in total body weight and body fat in young women aged 18 to 31 years. Thus, subjects with high calcium intake, corrected by total energy intake, and lower vitamin A intake gained less weight and body fat over two years in this randomized exercise intervention trial. PMID- 11194529 TI - Effect of meat replacement by tofu on CHD risk factors including copper induced LDL oxidation. AB - OBJECTIVE: To investigate the effect of replacing lean meat with a soy product, tofu, on coronary heart disease risk factors including serum lipoproteins, lipoprotein (a), factor VII, fibrinogen and in vitro susceptibility of LDL to oxidation. DESIGN: A randomized cross over dietary intervention study. SETTING: Free-living individuals studied at Deakin University. SUBJECTS: Forty-five free living healthy males aged 35 to 62 years completed the dietary intervention. Three subjects were non-compliant and excluded prior to analysis. INTERVENTIONS: A diet containing 150 grams of lean meat per day was compared to a diet containing 290 grams of tofu per day in an isocaloric and isoprotein substitution. Each dietary period was one month duration. RESULTS: Analysis of the seven-day diet record showed that diets were similar in energy, protein, carbohydrate, total fat, saturated and unsaturated fat, polyunsaturated to saturated fat ratio, alcohol and fiber. Total cholesterol and triglycerides were significantly lower, and in vitro LDL oxidation lag phase was significantly longer on the tofu diet compared to the meat diet. The hemostatic factors, factor VII and fibrinogen, and lipoprotein(a) were not significantly affected by the tofu diet. CONCLUSIONS: The increase in LDL oxidation lag phase would be expected to be associated with a decrease in coronary heart disease risk. PMID- 11194530 TI - The effect of lecithin supplementation on plasma choline concentrations during a marathon. AB - BACKGROUND: Previous studies have shown that plasma and urinary free choline concentrations decrease significantly during a marathon, and that these decreases may be associated with decreased performance. OBJECTIVE: In a pilot study, we sought to determine whether lecithin supplementation prior to a marathon would maintain plasma free and urinary choline concentrations and improve performance versus placebo. METHODS: 12 accomplished marathon runners, males (7) and females (5), 21 to 50 years of age were randomized to receive lecithin (4 capsules BID; PhosChol 900) or placebo beginning one day prior to the 2000 Houston-Methodist Health Care Marathon. The lecithin supplement provided approximately 1.1 g of choline on a daily basis (2.2 g total). Runners estimated finish time based on recent performance and training. Fasting, pre- and post-marathon plasma and a five-hour urine collection were analyzed for free choline and plasma for phospholipid-bound choline. Pre-race predicted, as well as the actual finish time, were recorded. RESULTS: All subjects completed the marathon. Plasma free choline decreased significantly in the placebo group and increased significantly in the lecithin group (9.6 +/- 3.6 to 7.0 +/- 3.6 nmol/mL vs. 8.0 +/- 1.2 to 11.7 +/- 3.6 nmol/mL, p = 0.001 for the delta between groups). No significant changes in plasma phospholipid-bound choline concentration were observed. There was a non significant decrease in urine free choline in both groups. Actual finish time was 256.3 +/- 46.3 minutes for the lecithin group vs. 240.8 +/- 62.0 for the placebo group and the actual:predicted time was 1.03 +/- 0.06 (lecithin) and 1.07 +/- 0.08 (placebo), p = 0.36. CONCLUSION: Short-term lecithin supplementation prior to a marathon maintains normal plasma free choline concentration during the race, but failed to improve performance. PMID- 11194531 TI - Revisiting the picky eater phenomenon: neophobic behaviors of young children. AB - OBJECTIVES: To compare picky eater behaviors (food neophobia) of children as toddlers and at 42 to 84 months of age and to assess their mothers' neophobic behaviors. METHODS: In a follow-up study of toddlers' picky eater behaviors, trained interviewers conducted four in-home interviews with mothers (n = 71) when their children were 42, 60, 72 and 84 months of age. Mothers reported children's diets (1 weekend day and 2 week days, 12 days total) and their behaviors; weight and height were measured. An additional interview at 48 months involved only mothers' behaviors. Nutritionist IV software, correlations, t tests and repeated measures ANOVA were used to determine nutrient intake, behavioral relationships and differences by picky eater status. Mothers' descriptions of the children's food neophobia and bothersome behaviors were analyzed by qualitative methods. RESULTS: Mothers reported children's neophobic behaviors at all ages. Mothers' and children's behaviors were significantly and consistently correlated for number of attempts before deciding an unfamiliar food was disliked (p < 0.01) and trying unfamiliar foods away from home (p < 0.01). Other behavioral associations were significantly related for some ages but not for all the children's ages. There were no significant differences by picky eater status for nutrient intake or height and weight at any age. Mothers most frequently attempted unfamiliar entrees away from home because of social setting/relationships. About 20% of mothers attempted unfamiliar foods or new recipes just because they were different. CONCLUSIONS: Findings suggest that some neophobic behaviors of children did not improve with maturity. Mothers' perceptions about their children's picky eater status were inconsistent over time. PMID- 11194532 TI - Relative weight, weight loss efforts and nutrient intakes among health-conscious vegetarian, past vegetarian and nonvegetarian women ages 18 to 50. AB - OBJECTIVE: To compare relative weight, weight loss efforts and nutrient intakes among similarly health-conscious vegetarian, past vegetarian and nonvegetarian premenopausal women. METHODS: Demographic data, lifestyle practices and weight loss efforts (by questionnaire), body mass index (BMI;kg/m2) and dietary intake (via multiple-pass 24-hour diet recall) were compared in a convenience sample of 90 current vegetarians, 35 past vegetarians and 68 nonvegetarians. RESULTS: Age (31.9 +/- 8.8), educational attainment, smoking status, alcohol use, physical activity and perceived health status were similar among the three groups of women. BMI did not differ by dietary pattern and averaged 23.7 +/- 4.7 for all women combined. Participants had intentionally lost > or = 10 pounds a mean of 2.1 times, and 39% of women perceived themselves to be overweight; again, no differences were observed among dietary groups. Dietary intakes of vegetarians and current nonvegetarians were consistent with current recommendations for macronutrient composition (< 30% fat, < 10% saturates). Compared to current nonvegetarians, current vegetarians had lower intakes of protein, saturated fat, cholesterol, niacin, vitamins B12 and D, and higher fiber and magnesium intakes. Vegetarians' mean vitamin B12 and D intakes were well below recommendations. CONCLUSIONS: Relative weight and weight loss efforts do not differ by dietary pattern among similarly health-conscious vegetarian and nonvegetarian women. The only differences in nutrient intake with potential health implications were vitamins D and B12. PMID- 11194533 TI - Double-blind controlled study on the effects of dietary diacylglycerol on postprandial serum and chylomicron triacylglycerol responses in healthy humans. AB - OBJECTIVE: The effects of dietary diacylglycerol (DG) on postprandial lipemia in healthy humans were investigated. METHODS: Forty normolipidemic male volunteers ingested fat emulsions containing either DG oil or triacylglycerol (TG) oil, at different doses: 10 g (n = 13), 20 g (n = 10) and 44 g (n = 17). Two test emulsions were given at seven-days intervals in random order. Fatty acid compositions of the test oils had been adjusted to be equal. Fasting and postprandial serum lipid concentrations in each group and plasma lipoprotein lipids in the 20 g-fat ingestion group were measured during the postprandial intervals. RESULTS: When DG emulsion was ingested, serum TG concentrations were significantly lower (p < 0.05) in the late postprandial phase, i.e., 4 hours, 6 hours as compared to the TG emulsion. The magnitude of postprandial lipemia (the area bounded by the curve above the fasting concentration) after ingestion of 44 g-DG emulsion was significantly less than that of 44 g-TG emulsion (6.54 +/- 5.12 and 8.45 +/- 7.54 mmol x h/L, mean +/- SD, respectively). Chylomicron TG, cholesterol, and phospholipid concentrations at 4 hours after ingestion of DG emulsion were significantly lower (p < 0.05) than those after the ingestion of TG emulsion at the same time point. No marked differences were observed for VLDL, LDL and HDL lipids between the test emulsions. CONCLUSION: In the usual range of fat intake (10-44 g), postprandial response after ingestion of DG emulsion was significantly less than that after ingestion of TG emulsion in healthy human subjects. PMID- 11194534 TI - Feeding tolerance in preterm infants: randomized trial of bolus and continuous feeding. AB - OBJECTIVE: To test the hypothesis that continuous gastric infusion (CGI) is better tolerated than intermittent gastric bolus (IGB) in small very low birth weight (VLBW) infants. DESIGN: Two-center, prospective, randomized, unmasked clinical trial. PATIENTS: 28 VLBW infants (birth weight <1250 g). A strict feeding protocol was followed. INTERVENTION: Patients were randomized to IGB or CGI. MAIN OUTCOME MEASURES: Time to reach full feeds (160 cc/kg/d)(by design and real), daily weight, caloric intake, residual gastric volume and type of feeding (formula vs. human milk vs. both). RESULTS: Five infants failed to complete the study because of death (n = 4) or protocol violation (n = 1). The two groups did not differ by birth weight or gestational age; infants fed via IGB reached full feeds earlier (p = 0.03) and had less delay in reaching full feeds than infants fed via CGI. CONCLUSION: Contrary to our hypothesis, gravity IGB is more effective than CGI in improving feeding tolerance in small VLBW infants. PMID- 11194535 TI - Development of a self-assessment instrument to determine daily intake and variability of dietary vitamin K. AB - OBJECTIVE: To develop and validate a brief, self-assessment instrument (K-Card) to determine daily variations in dietary vitamin K1 (phylloquinone) intake for use in patients receiving oral warfarin anticoagulant therapy. METHODS: The K Card was designed to include a checklist of selected common foods and beverages providing > or = 5 microg vitamin K per serving in American diets and items with lower vitamin K content typically consumed in quantities which contribute significantly to total vitamin K intake. The K-Card was validated against records of weighed food intake from thirty-six healthy volunteers, 20 to 40 and 60 to 80 years of age, whose phylloquinone intakes and plasma concentrations had been previously measured by the Metabolic Research Unit, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA USA. Future use of the K-Card by patients was simulated by a single investigator using 108 one day weighed food records to estimate phylloquinone intakes. Dietary phylloquinone calculated from the K-Card was compared to the values of phylloquinone intake from the diet records collected on the same days, and to fasting plasma phylloquinone concentrations obtained from the same individuals on the following day. RESULTS: The mean dietary phylloquinone intake (+/- SEM) was 138.8 +/- 15.7 microg for the K-Cards compared to 136.0 +/- 15.8 microg for the diet records (p = 0.067). Bland-Altman limits of agreement between quantities of dietary phylloquinone calculated from the K-Card and values obtained from the weighed food records were +/- 38 microg. CONCLUSION: In this simulation, the K-Card provided an accurate estimate of dietary phylloquinone intake and therefore deserves further testing for use by patients receiving coumarin-based anticoagulant therapy to determine whether variability in dietary patterns contributes to disruptions in anticoagulant drug efficacy and safety. PMID- 11194536 TI - Results of the Azizkhan procedure for long-term suprastomal tracheomalacia. AB - One of the reasons of failure to decannulate patients after airway surgery or long-term tracheostomy is suprastomal tracheomalacia. We present 7 cases with long-term tracheostomies treated by an anterior cricoid suspension described by Azizkhan in 1993. Prior to surgery, other causes of airway obstruction, as well as the presence of gastroesophageal reflux disease should be ruled out. All of them are decannulated. This procedure is a safe surgical technique, easily reproducible and with low costs. PMID- 11194537 TI - Surgery of subglottic stenosis in neonates and children. AB - The excellent management of patients in the different Intensive Care Units has decreased mortality but, as a side effect, we have to treat an increasing number of patients with airway problems secondary to prolonged intubation. The clinical records of patients diagnosed of acquired or congenital subglottic stenosis (SE) between 1990 and 1995 were retrospectively reviewed. Types of treatment included conservative, endoscopic, and open surgery: anterior cricoid split (ACS), anterior laryngotracheoplasty (ALTP) and anteroposterior laryngotracheoplasty (APLTP). 46 patients had SE: 7 congenital and 39 acquired. According to Cotton's classification 13 had grade I, 16 grade II, 12 grade III and none grade IV. Eleven of twelve cases treated conservatively did well (92%); one out of six patients managed endoscopically required further surgery (7%); good results were obtained in 5 of 7 cases treated by ACS (71 %); 8 out of 9 patients treated by ALTP did well (89%) and 7 out of 8 managed by APLTP had good results (87.5%). One iatrogenic suture dehiscence required further surgery. There is no statistical difference in the complication rate between patients treated conservatively and those treated by open surgery, while the mean hospital stay was higher in the latter (p < 0.05). An appropriate surgical technique should be offered to those patients with SE who do not do well with conservative management, since these techniques have yielded good results with a low rate of complications. Long-term follow-up shows the absence of recurrence. PMID- 11194538 TI - A new and successful chance in surgical treatment of gastrooesophageal reflux in severely neurologically impaired children: Bianchi's procedure. AB - AIM: Neurologically impaired (NI) children present with neuromuscular incoordination and severe gastroesophageal reflux (GER). In these cases, Bianchi has proposed total oesophagogastric dissociation (OGD) as a primary procedure and not only after failed fundoplication. METHODS: Anthropometric and laboratory data, incidence of respiratory symptoms, days of hospitalisation, time of feeding, stool frequency and quality of life were tested preoperatively and after OGD over a 12-month period in 13 severe NI patients. RESULTS: Results are shown in Table 1. We also recorded improvement in quality of life, based on communication by the person responsible for the care of the subject, and determined by psychological interviews. CONCLUSIONS: OGD is a successful and feasible procedure and can be included as a primary definitive surgical treatment in individualised nutritional rehabilitation planning for each severe NI child. PMID- 11194539 TI - Gastric electrical activity normalises in the first decade of life. AB - AIM: Electrogastrography (EGG) is emerging as a non-invasive modality for clinical investigation, especially in children. Yet the results of EGG are influenced by many factors, including age. The objective of this study was to establish the relationship between EGG parameters and age. METHODS: Fasting surface EGG (Digitrapper, Synectics) was recorded on 24 healthy boys. The data were analyzed using ANOVA, taking p < 0.05 as being statistically significant. RESULTS: The age of the boys studied ranged from 1.0 to 11 years (mean = 6.0 years). The percentage of bradygastria was high, accounting for 34% of the recording. Normal rhythm increased (p = 0.013) and the bradygastria decreased with age (p = 0.026). The dominant frequency instability coefficient also decreased to a certain extent with age (p = 0.065). CONCLUSION: Compared to the adult population, bradygastria is common in children. The EGG progressively approaches adult pattern as the enteric development matures in the first decade of life. This justifies the conservative approach in managing conditions like gastro-oesophageal reflux in young children. PMID- 11194540 TI - Venoocclusive liver disease (VOD) as a complication of Wilms' tumour management in the series of consecutive 206 patients. AB - In 4 years (1993-1996) 206 pts. with nephroblastoma were treated. All children were treated according to SIOP 93-01 protocol. Overall survival was 92%. In 27 cases hepatotoxic events occurred. In 10 cases, venoocclusive liver disease (VOD) was diagnosed. VOD is a syndrome associated with hepatomegaly, sudden weight gain or ascites and jaundice. It results from damage to the endothelium of hepatic venules and necrosis of central hepatocytes with subsequent proliferation of fibrous tissue and occlusion of the central hepatic veins. Dactinomycin is one of the drugs considered responsible for its development. Mean age of VOD patients was 4 yrs, however 3 of them were below 1 yr. In all cases, VOD occurred during postoperative chemotherapy (mean 16 th week of treatment). All patients received dactinomycin and vincristine. Five children with right kidney tumors underwent post-operative abdominal irradiation. Main VOD symptoms were hepatomegaly and ascites (80%). Hypertransaminasaemia, as well as, on ultrasound, gallbladder wall thickening and/or free abdominal fluid were observed. Median VOD duration was 27 days and its course was usually temporary and self-limiting. However, in 2 cases recurrent VOD episodes were noted. All children received supportive treatment only. In 6 cases, VOD resulted in chemotherapy delay or drug reductions, while in 4 others chemotherapy was completed preliminarily. Nevertheless it did not affect patients' outcome overall survival in VOD group was 90%. CONCLUSIONS: Total 5% VOD frequency is similar to other reports. Infants and children receiving abdominal irradiation seem to be at special risk of VOD development. PMID- 11194541 TI - Is there a correlation between organochlorine compounds and undescended testes? AB - Some pesticides and synthetic chemicals are known to act as hormonal modulators, often possessing oestrogenic activity (xenooestrogens). They are persistent and accumulate in fatty tissue. Aim of our study is to address the question, whether a selection of such compounds is to be found in the fatty tissue of children undergoing surgical procedures and whether there are differences in values obtained from patients with or without undescended testes. Fat samples of 48 patients, 18 of whom had undescended testes, were examined by high-resolution gas chromatography and mass spectrometry for DDT and metabolites, polychlorinated biphenyls (PCB), toxaphenes, hexachlorocyclohexane (HCH), chlorinated cyclodienes and chlorinated benzenes. We were able to find accumulation of all substances in every patient. Statistical analysis revealed a highly significant difference between patients from the control group and those from the undescended testes group for two compounds, namely heptachloroepoxide (HCE) and hexachlorobenzene (HCB), increased values being found in the patients with undescended testes. Since the aetiology of this entity is unknown in most of the cases, prenatal exposure to exogenous oestrogens is an attractive and plausible hypothesis. In order to confirm this, some questions will have to be answered in further studies: effect of exposure to xenooestrogens during a specific period of development, probable role of other substances with proven or suspected hormonal activity, potential synergism of such compounds and differences in individual susceptibility. PMID- 11194542 TI - First Spanish Trauma Registry: analysis of 1500 cases. AB - OBJECTIVES: To develop the first Spanish Pediatric Trauma Registry to collect and evaluate infomation concerning aspects of injuries in our pediatric population. METHODS: From January 1995 to August 1998, 35,946 children younger than 16 years were treated in our hospital for acute injury: 1500 were admitted and included in our database. Our file registry consists of 108 data points including: patient identification, type, place and mechanism of injury, pre-hospital care, transport, assessment on admission, severity scores, diagnostic studies, injuries, treatment morbidity and mortality. RESULTS: Accidents were more frequent in males (68%) than in females. The predominant age group was 12-15 years of age (34%). Accidents were more frequent in the street (35.1%) than at home (18.9%) or school (13%). Falls and traffic-related accidents were the leading cause of injury (39% and 21.2%, respectively). Two hundred and thirty five (15.7%) had a Pediatric Trauma Score < or = 8. Fifty of these sustained multiple trauma (33%) (Injury Severity Score > or = 15). Musculoskeletal and head trauma were the most frequent injuries (48.5% and 42.0%, respectively). Surgical or orthopedic procedures were performed in 906 patients (56.5%). The average length of stay was 4.5 days (range 1-93 days). Functional impairment in children older than 4 years of age was found in 413 children (33.3%). We encountered 7 deaths in the 1500 patients, or an overall mortality of 0.5%. These 7 deaths were only seen in the I.S.S. > or = 15 group (50 patients) with 14% mortality. CONCLUSIONS: The goals of this Registry are to establish the epidemiology of our injured pediatric population, to review patient care, to develop prevention programs and to compare results with other centers so that potential deficiencies can be corrected. PMID- 11194543 TI - Elastic stable intramedullary nailing (ESIN) provides good long-term results in pediatric long-bone fractures. AB - The present study evaluates the long-term outcome of elastic stable intramedullary nailing (ESIN) in children with long-bone shaft fractures. 70 patients were examined, the present mean age of patients was 12.7 (+/- 3.26) years, mean time interval since surgery was 3.1 (+/- 1.49) years. Following ESIN at the lower extremity (23 femur fractures, 14 tibia fractures), keloid formation was remarkable in one patient, range of motion (ROM) was adequate in all but one boy (extension deficit of the hip of 10 degrees). Overall leg length discrepancy was +4.1 mm (+/- 5.2 mm) following ESIN for femur fracture and +3.2 mm (+/- 6.4 mm) following tibia fracture. Radiologically, all fractures had healed and no signs of avascular necrosis (AVN) could be detected. Malalignment was documented in one girl following tibia fracture (valgus of 12 degrees). Assessment of the upper extremity (28 forearm fractures, 5 humerus fractures) revealed keloid formation in 5 children. Impaired ROM was found in three children following ESIN for a forearm fracture (limited pro-/supination). Radiological controls detected one case of retrocurvation of the humerus (12 degrees, polytrauma patient) and one varus deviation of the radius in a 10-year old boy. Questioning the children about their opinion of the treatment, 93% considered the cosmetic results as good (6% fair), they judged the functional ability as perfect in 91% (9% fair) and 93% expressed great overall content (6% fair, 1% poor). In conclusion, ESIN provides good long-term results and can be a beneficial method for children with long-bone fractures. PMID- 11194544 TI - Small-bowel perforation in very low birth weight neonates treated with high-dose dexamethasone. AB - INTRODUCTION: Early postnatal treatment with high doses of corticosteroids may be effective in reducing the duration of mechanical ventilation in very low birth weight infants at risk for bronchopulmonary dysplasia. However, serious side effects may occur. MATERIAL AND METHODS: A retrospective study on 5 very low birth weight neonates, mean (+/- SEM): gestational age range 27.5 +/- 2 weeks, mean birth weight (+/- SEM): 836 g +/- 169 referred between April 1997 and October 1998 from a single academic neonatal intensive care unit to our tertiary pediatric surgical center with the diagnosis of intestinal perforation. During the same period, 60 very low birth weight infants have been treated in that unit following a standardized protocol including surfactant for respiratory distress syndrome and high-dose dexamethasone to prevent bronchopulmonary dysplasia. RESULTS: Pneumoperitoneum was diagnosed between 6 to 9 days after birth. Clinically, all babies remained surprisingly stable. An isolated ileal perforation, without sign of necrotizing enterocolitis, was found at laparotomy in each patient. A limited intestinal resection was performed, with primary end toend anastomosis (3 cases) or with transient ileostomies (2 cases). Surgical outcome was favorable in all patients. CONCLUSION: isolated intestinal perforation may be a complication of the preventive treatment of chronic lung disease with high-dose corticosteroids in very low birth weight infants. Conversely, corticosteroids may reduce the clinical signs and the multiple organ dysfunction associated with an abdominal drama, explaining the very good surgical prognosis of these newborns. Attention must be paid to an insidious pneumoperitoneum. PMID- 11194545 TI - Successful EXIT (ex utero intrapartum treatment) procedure in a fetus diagnosed prenatally with congenital high-airway obstruction syndrome due to laryngeal atresia. AB - Congenital high-airway obstruction syndrome (CHAOS) is due to rare malformations and has been reported previously in only few cases. If the diagnosis can be made prenatally, the ex utero intrapartum treatment (EXIT) procedure may be life saving. A healthy 28-year old nulli-para was referred because of isolated ascites found at gestational week 16 during routine ultrasound scan. Repeated scans showed overdistended hyperechogenic lungs with inverted diaphragm and a dilated trachea, which was interpreted as a CHAOS resulting from laryngeal atresia. The ascites eventually disappeared. An EXIT procedure was performed at 35 weeks of gestation. Anesthesia of the mother was induced with thiopental, succinylcholine and fentanyl followed by intubation, and maintained with isoflurane and nitrous oxide. A low abdominal midline incision was performed followed by a low transverse incision of the uterus. The fetal head, right arm and shoulder were delivered and intramuscular anesthesia was administered to the fetus. Immediate laryngoscopy confirmed the diagnosis and a tracheostomy was therefore performed. Surfactant was given after a few minutes of ventilation. Compliance improved and when the fetus was easy to ventilate, it was delivered. The baby is developing normally at 18 months of age. Surgical correction of the malformation will be performed after two years of age. It is concluded that some fetuses with a prenatal diagnosis of CHAOS can benefit from the EXIT procedure at delivery. This necessitates a multidisciplinary management team. PMID- 11194546 TI - Prophylactic thyroidectomy in the treatment of thyroid medullary carcinoma. Age for surgery? AB - Since the association of RET proto-oncogene mutations and medullary thyroid carcinoma in children there has been much discussion regarding timing of surgery. Our study group was formed from a brother and sister (8 and 5) and 3 brothers (9, 13, 16) selected on the basis of a positive family history for thyroid medullary carcinoma. Histological examinations of the thyroidectomy specimens showed that the 8- and 9-year old had microinvasive carcinoma and the remaining three had C cell hyperplasia. Our recommendation is for prophylactic thyroidectomy for children with RET proto oncogene mutations at an early age, clearly before age 5. PMID- 11194547 TI - Spondylothoracic dysplasia with diaphragmatic defect: a case report with literature review. AB - Spondylothoracic dysplasia (Jarcho-Levin syndrome) is a syndrome of unknown etiology. We describe a new case with diaphragmatic eventration. Literature review for cases of Jarcho-Levin syndrome with diaphragmatic defects, which were six cases, revealed that renal affection increased when diaphragmatic defects associate the syndrome with pulmonary hypoplasia. Thus, the subgroup of spondylothoracic dysplasia with diaphragmatic defect is a more severe subgroup of the syndrome rather than the other forms of this syndrome. Relating the described anomalies in this case and that of the literature cases to the known embryological basis may point to a pivotal developmental link between lung, kidney and diaphragm, possibly the posterior mesenchyme. PMID- 11194548 TI - Neuroblastoma and bronchogenic cyst: a rare association. AB - A few of the known associations between paediatric cancer and congenital anomalies are attributable to contiguous-gene syndromes. Neuroblastoma (NB) has been linked with an excess of gastrointestinal malformations, but there is a significant scarcity of associated respiratory anomalies. We report on two children having an abdominal NB and a bronchogenic cyst diagnosed simultaneously and in different order of appearance. Both masses were removed in separated procedures, taking into account the priority and the time sequence of chemotherapy. Literature is reviewed, checking that the genetic basis for this association is supported by speculations about the oncogene RON. PMID- 11194549 TI - In vitro development of green fluorescent protein (GFP) transgenic bovine embryos after nuclear transfer using different cell cycles and passages of fetal fibroblasts. AB - Nuclear transfer using transfected donor cells provides an efficient new strategy for the production of transgenic farm animals. The present study assessed in vitro development of nuclear transfer embryos using green fluorescent protein (GFP) gene-transfected bovine fetal fibroblasts. In experiment 1, bovine fetal fibroblasts (BFF) were transfected with linearized pEGFP-N1 by electroporation, and the enucleated oocytes were reconstructed by nuclear transfer of transfected cells (BFF-GFP). The rates of blastocyst formation did not differ significantly between BFF and BFF-GFP (18.2% v. 15.6%). In experiment 2, before nuclear transfer, the donor cell stage was synchronized by serum deprivation or forming a confluent monolayer. The rates of cleavage (67.1% v. 71.8%) and blastocyst formation (15.8% v. 15.5%) did not differ between confluent and serum-starved cells after nuclear transfer. In experiment 3, the effects of different passages of donor fibroblast cells on the development of nuclear transfer embryos were investigated. Donor cells from 'early' (at passage 8-16) showed better blastocyst development (18.9%) than those from 'late' (at passage 17-32; 10.5%). In conclusion, this study suggests that transgenic somatic cell nuclei from early passages can be reprogrammed more effectively than those from late passages. In addition, GFP, a non-invasive selection marker, can be used to select transgenic nuclear transfer embryos. PMID- 11194550 TI - In situ pH measurements of the Syrian hamster uterus during early pregnancy to determine the role of pH in zona pellucida loss in vivo. AB - The mechanisms of zona pellucida (ZP) loss in peri-implantation hamster embryos in vivo versus in vitro are distinctly different. To investigate if ZP loss in vivo is the result of transient uterine pH changes, the luminal pH of the pregnant uterus was measured during the ZP loss period. Prior to ZP loss, pH was 7.30 +/- 0.05 (mean +/- SE; left uterine horn) and 7.35 +/- 0.03 (right horn). During ZP loss, pH was 7.26 +/- 0.07 (left) and 7.35 +/- 0.03 (right), and after embryo attachment, 7.25 +/- 0.02 (left) and 7.27 +/- 0.02 (right). None of these values are statistically different. The pseudopregnant uterine pH was 7.30 +/- 0.04 (left) and 7.31 +/- 0.04 (right), not statistically different from each other or from pregnant uteri. Blastocyst ZP loss in vitro (pH 3.0-8.5) occurred only at pH 3.0. Loss of ZP occurred in uterine flushings from pregnant or pseudopregnant hamsters, evidence that ZP loss is related to uterine factors. Complete ZP loss occurred at pH 6.8, but was incomplete at pH 6.6, 7.0 and 7.2. No ZP loss occurred in uterine flushings from non-mated females. In summary: (i) a change in uterine pH does not cause ZP loss in vivo in the Syrian hamster; (ii) a pH-sensitive factor in pregnant and pseudopregnant uterine fluid is responsible for ZP loss. PMID- 11194551 TI - Intrauterine insemination in sows with reduced sperm number. AB - Usually 2-3 x 10(9) sperm per insemination are used in pigs. In other species it has been shown that changing the site of insemination allows a reduction in the amount of sperm per insemination dose. The goal of this study was to determine the minimal number of sperm that can be used, without a reduction in either the pregnancy rate or the mean litter size, using surgical deep intrauterine insemination in sows after weaning. Three different sperm concentrations (5 x 10(8), 1 x 10(8) and 1 x 10(7) sperm cells extended in 0.5 mL Androhep) were inseminated into the tip of each uterine horn. In addition two groups of control sows were inseminated once intracervically 24-32 h after the first signs ofoestrus with 1 x 10(9) and 3 x 10(9) sperm in 80 mL Androhep extender. Animals that became pregnant were allowed to farrow normally. No significant differences were observed between groups inseminated surgically with the three different sperm dosages with respect to pregnancy or farrowing rate. There was also no significant difference between the results of these groups and the results obtained from the non-surgically inseminated control groups. Neither the mean number of live-born nor stillborn piglets was significantly different between the surgically inseminated groups and the control groups. The total number of piglets born in each group was also not statistically different. The data show that the sperm number to be used for surgical insemination can be lowered without loss of the fertilization potential and may be used in the field as soon as a suitable insemination device is available. PMID- 11194552 TI - Development of reconstituted pig embryos by nuclear transfer of cultured cumulus cells. AB - This study tested the effects of oocyte collection method, activation protocol and maturational age of recipient oocytes on the in vitro development of nuclear transfer embryos reconstructed with cultured cumulus cells. Cumulus cells synchronized in G0/G1 phase by serum-starvation culture were transferred into enucleated oocytes that were collected by aspiration or dissection method and cultured for 33 or 44 h. Reconstituted embryos were activated with a combination of calcium ionophore A23187 or electric pulse and cycloheximide (CHXM), and cultured for 6 days. Oocyte collection methods, activation treatment in the presence of cytochalasin B and activation protocols did not affect the developmental rate of embryos reconstituted with 44-h-matured recipients. However, the development of embryos reconstituted with 33-h-matured recipients was significantly improved (P<0.05) by activation with the combination of electric pulse and CHXM. The present study shows that reconstituted porcine embryos derived from cultured cumulus cells can develop to the blastocyst stage, and that their development can be improved by reconstruction with young oocyte cytoplasts following activation with a combination of electric pulse and CHXM. PMID- 11194553 TI - Non-invasive monitoring of reproductive status in wild mongoose lemurs (Eulemur mongoz). AB - Endocrine profiles were investigated in wild and captive mongoose lemurs (Eulemur mongoz; Lemuridae) by analysing faecal progestagens and oestrogens. Oestrous cycle characterization was not possible, as most females appeared to conceive during the first oestrus of the breeding season. Conception was preceded by a pseudo-oestrus with no discernible luteal phase. Pseudo-oestrus and oestrus identification was possible by investigating the oestrogen:progestagen ratio. Pregnancy was reliably determined approximately 47 days after conception, when progestagen and oestrogen excretion increased above breeding season concentrations. Gestation was further characterized by high progestagen concentrations and a decline in oestrogen excretion 70-80 days after conception. Post partum, progestagens declined, but oestrogen excretion increased to exceed breeding season concentrations. In the wild group, a nulliparous daughter conceived while still a member of her natal group and aborted after 70-80 days of pregnancy at which time progestagens had declined but oestrogens remained high. Comparisons with other strepsirhine primates suggest that pseudo-oestrus followed by conception at first oestrus may be prevalent in lemurs. Gestational progesterone profiles vary between species, but a delayed increase in oestrogens during pregnancy could be common to all strepsirhines, although oestrogen levels during the final trimester of pregnancy differ between lemurs and lorises. Methodological investigations showed that prolonged storage of faeces in ethanol is viable and that the presence of undigested vegetable matter in the faecal pellets had no effect on the interpretation of hormone profiles. PMID- 11194554 TI - The viability of transferred sheep embryos after long-term cryopreservation. AB - The survival to term of 414 sheep embryos, thawed and transferred after conventional cryopreservation and storage for 13 years, was evaluated. A concurrent experiment involving the transfer of vitrified embryos to 91 ewes and artificial insemination of 51 ewes with frozen-thawed semen from sires of the long-term cryopreserved embryos provided forms of control treatments. The donor ewes had a mean ovulation rate of 10.9, and 7.1 embryos per ewe were cryopreserved. Each recipient ewe received two embryos and pregnancy was assessed at Day 18, Day 54 and term. The pregnancy rate was lower in the long-term embryo group than the artificial insemination group at Day 18 (P<0.01) and Day 54 (P<0.05), although the difference at term (31% v. 49%) was not significant, with the vitrified embryo group being similar to the long-term group. Embryo survival to birth was 21%, with the majority of loss (80%) occurring by Day 18. The later stage of development and higher grade of transferred embryos and the older age of donor ewes resulted in a significantly higher (P<0.01) pregnancy rate at Day 54 and term, and percentage of lambs born and weaned. Other effects of donor ewes (genotype, superovulation treatment, number of ovulations and embryos cryopreserved) were not significant. Implications for the design of genetic evaluation and germplasm conservation programmes using embryo cryopreservation technology are discussed. PMID- 11194555 TI - Protein synthesis and phosphorylation by elongating 13-15-day-old cattle blastocysts. AB - Most early embryonic loss in cattle occurs during the period of blastocyst formation and elongation. In this study de novo protein synthesis and phosphorylation by 13-15-day-old cattle blastocysts was determined. Blastocysts were classified by dimension into spherical, ovoid and elongated stages and cultured under oil for 4 h in drops of KSOM medium containing either 35S methionine or 32P-orthophosphate. Protein content increased with shape from spherical to ovoid to elongated. There were differences (P<0.05) within and among days in the percentage of radiolabel incorporated. Incorporation of 35S methionine increased with embryo protein content. However, incorporation of 35S methionine into TCA-insoluble material, expressed per microg of protein, decreased with shape (P<0.001) with more than a 10-fold difference between spherical and elongated 13-day-old blastocysts. Incorporation of 32P orthophosphate also tended to decrease with shape, with a 3-fold difference between spherical and elongated Day 13 blastocysts. It was concluded that, from Day 13, protein synthesis and phosphorylation, when expressed per unit of protein, decreased from a much higher level, which in the present study was around the time the blastocysts began to elongate. PMID- 11194556 TI - Pituitary responsiveness to diurnal and nocturnal GnRH pulses in melatonin treated ewe lambs. AB - It has been shown that oral administration of melatonin to Suffolk ewe lambs, from 10 weeks of age onwards, advances the onset of puberty compared with control lambs maintained under the same natural photoperiod. Luteinizing hormone (LH) pulse frequency at 20 and 26 weeks of age was unchanged by melatonin. However, LH pulse amplitudes greater than 1 ng mL(-1) were consistently observed in melatonin treated lambs, suggesting either a high responsiveness of the pituitary gland to endogenous gonadotrophin-releasing hormone (GnRH) pulses, or a large amount of GnRH released by each pulse. The purpose of the present study was to assess the pituitary responsiveness to six diurnal and six nocturnal exogenous pulses of GnRH (10 ng kg(-1) bodyweight) in melatonin-treated ewe lambs (3 mg melatonin daily at 1600 hours, from 10 weeks of age; n = 5) and control lambs of the same age (n = 5), born in the spring and kept under natural photoperiod. Pulses of GnRH were given intravenously at 60-min intervals by means of an indwelling jugular catheter from 0900 to 1400 hours and from 2100 to 0200 hours to ewe lambs of 20 and 26 weeks of age. Blood samples were collected at 10-min intervals using a contralateral jugular vein catheter from 1 h before and up to 1 h after the last GnRH pulse. The difference (delta) between plasma LH concentrations at 0 min and the greatest concentration of LH after each GnRH pulse was calculated and compared in the same group. The total area under the GnRH response curve (AUC) was also calculated and compared within and between the groups. The AUC of melatonin-treated lambs (66.1 +/- 5.94 and 52.24 +/- 7.42 ng mL(-1)/6 h, diurnal and nocturnal respectively) was greater than that of control lambs (39.42 +/- 4.29 and 32.82 +/- 3.6 ng mL(-1)/6 h diurnal and nocturnal respectively; P<0.05) at 20 weeks of age. At 26 weeks of age, only the diurnal total AUC was greater in melatonin-treated lambs than in control lambs (60.17 +/- 7.98 and 29.8 +/- 5.02 ng mL(-1)/6 h respectively; P<0.05). Delta LH concentrations in response to the first diurnal pulse of GnRH were greater than those in response to the fifth diurnal GnRH pulse (P<0.05) in melatonin-treated lambs of 20 weeks of age. Also, the delta LH concentrations in response to the first three diurnal GnRH pulses were greater than to the last three nocturnal pulses of GnRH (P<0.05). Delta LH concentrations were greater in response to the second diurnal pulse of GnRH than to the last three diurnal GnRH pulses, and greater than the responses to the first and the last four nocturnal GnRH pulses (P<0.05), at 26 weeks of age in melatonin-treated lambs. The response to nocturnal pulses of GnRH was similar. In control lambs, the responses to diurnal and nocturnal GnRH pulses were similar at 20 and 26 weeks of age. These results suggest that melatonin enhances the pituitary responsiveness to GnRH pulses in ewe lambs. PMID- 11194557 TI - Characterization of the spermiation response, luteinizing hormone release and sperm quality in the American toad (Bufo americanus) and the endangered Wyoming toad (Bufo baxteri). AB - Spermiation and LH release in response to several methods of LHRH administration were assessed in the American toad (Bufo americanus), and the most successful method was tested in the endangered Wyoming toad (Bufo baxteri). Specific objectives were to: (1) compare spermiation responses and plasma LH concentration after invasive and non-invasive LHRH treatments; (2) evaluate sperm production in response to different LHRH dosages; (3) characterize the timing of sperm release post LHRH treatment; and (4) assess sperm quality (motility, viability, morphology and acrosomal status). Male American toads were administered 4 microg LHRH by one of four routes: (1) intraperitoneal injection (i.p.); (2) subcutaneous injection (s.q.); (3) dorsal dermis absorption (d.d.a.); and (4) ventral dermis absorption (v.d.a.). Aspermic urine only was collected from saline treated controls and d.d.a. animals. Several v.d.a. animals released spermic urine; however, all LHRH-injected toads released spermatozoa. I.p. animals produced higher sperm and LH concentrations than s.q. animals. The spermiation response in animals treated i.p. with 1 microg LHRH was similar to that in animals treated with 4 microg, but lower LHRH dosages tested produced inferior responses. Sperm production in responsive animals increased over time during the 12-h sampling interval. Regardless of treatment, most American toad spermatozoa were motile, viable, and acrosome-intact. Endangered Wyoming toads were treated i.p. with 4 microg LHRH, and spermic urine was collected. Although most spermatozoa were viable and acrosome-intact, a considerable percentage possessed structurally abnormal heads. A single i.p. injection of LHRH appears to be a reliable and safe method for controlling spermiation in toads and may be useful for assisting endangered amphibian propagation. PMID- 11194558 TI - Polo-like kinase expression in normal human endometrium during the menstrual cycle. AB - The enzyme, polo-like kinase (PLK), is a mammalian serine/threonine kinase involved in cell cycle regulation. A great deal of evidence regarding the role of PLK in the cell cycle has been obtained through studies of cultured cells, though little is known about its function or even expression in vivo. The endometrium undergoes rapid proliferation and differentiation under ovarian steroid hormone control during the 28-day cycle. Thus, normal endometrium provides an excellent model in which to study the hormone dependency of PLK expression. In the present study, we examined the features of PLK expression in 20 samples of normal human endometrium during the menstrual cycle. The expression of Ki-67 and proliferating cell nuclear antigen (PCNA) were also examined as markers of proliferation. Immunohistochemical studies showed that PLK staining was detected in the basement membrane of many endometrial glands, stromal cells, and some endothelial cells. The number of PLK-positive endometrial gland cells was significantly higher in the late proliferative phase (19.16% +/- 4.98%) and the early secretory phase (19.28% +/- 4.99%) than in the early proliferative phase (2.60% +/- 2.33%) or the late secretory phase (5.76% +/- 2.16%) (P<0.0001). PLK expression seemed to be correlated with the expression of Ki-67 and PCNA in many endometrial glands and stromal cells particularly in the late proliferative phase, reflecting a role of PLK in cellular proliferation. Nevertheless, in the early secretory phase, at which point the expression of Ki-67 and PCNA decreased in endometrial glands, PLK was strongly expressed. This finding suggests that PLK may have some post-mitotic functions in certain specialized cell types. Although the highest expression of PLK was observed in the late proliferative and the early secretory phases, the expression drastically decreased in the late secretory phase. These findings, taken together, indicate that the expression of PLK in normal endometrium fluctuates over the course of the menstrual cycle, suggesting in turn that PLK is associated with hormone-dependent cellular proliferation and that hormone functions may be involved in its regulation. PMID- 11194559 TI - Influence of relative size at birth on growth and glucose homeostasis in twin lambs during juvenile life. AB - The effect of differences in size at birth on growth and glucose homeostasis between female twin lambs during juvenile life was examined. Twenty-six sets of twins were entered into the study, of which ten were used for organ sampling at birth and 16 were studied over the first year of life. Eleven sets were defined as being mismatched for birthweight as the weight difference between twins was >25%, with light lambs weighing 4.1 +/- 0.3 kg and heavy lambs weighing 5.1 +/- 0.1 kg. All remaining twins were matched in bodyweight, weighing 4.6 +/- 0.5 kg. During the rapid period of juvenile growth (i.e. one, three and six months of age) and following stabilization of bodyweight (i.e. 12 months of age) glucose tolerance tests were performed by intravenously injecting 0.8 mg kg(-1) bodyweight glucose. This was followed the next day with an insulin tolerance test, performed by intravenously injecting 0.08 units kg(-1) bodyweight insulin. At birth there were no differences in organ weight as a fraction of total bodyweight between matched and mismatched twins, but the ratio of liver to brain weight was lower in light compared with heavy twins. Light lambs remained lighter than their twins up to six months of age, and crown-rump length was also shorter. At one and three months of age there were no differences in basal plasma glucose concentrations between the groups, but glucose tolerance was greater in light compared with heavy lambs at one and six months of age. Insulin tolerance was greater in light compared with matched lambs at one and six months of age. In conclusion, it has been shown that size at birth of one twin in relation to its co-twin is one factor determining glucose regulation during postnatal life. This not only affects glucose and insulin tolerance but also growth over the first six months of age. PMID- 11194560 TI - Vasoactive intestinal peptide influences hatching of ovine blastocysts. AB - Expanded blastocysts collected from superovulated Sarda ewes were divided at random into four groups for culture in a simple medium that does not support blastocyst hatching (CZB) or a complex medium that is permissive to hatching (TCM 199), with or without vasoactive intestinal peptide (VIP), a known embryo mitogenic peptide. Plasminogen activator (PA) secretion after 24 h of culture, and the number of cells, diameter of blastocysts and hatching rate after 48 h of culture were compared. The results showed an increase in hatching rate (78.6 v. 6.7%; P<0.01), diameter and number of cells (220.89 v. 210.44 microm, P<0.01 and 246 v. 232, P<0.01 respectively) and caseinolytic areas (1.33 v. 0.92 cm, P<0.01) of blastocysts cultured in TCM 199 compared with those cultured in CZB. Supplementation of the culture media with VIP increased these parameters in CZB (P<0.01) and partially in TCM 199. In particular, cell number, diameter and PA activity were significantly higher (P<0.01) after culture with VIP in both media. Immunoneutralization of exogenous VIP in culture with anti-VIP antibody caused a decrease in the hatching rate (P<0.01) of embryos cultured in medium with VIP, similar to the rate in unsupplemented CZB (P<0.01). These results suggest a receptor-mediated response. In immunohistochemical studies, VIP was shown to bind receptors in hatched blastocysts demonstrating the VIP-receptor interaction, and VIP receptors of approximately 150 kDa were revealed by electrophoretic studies. In conclusion, ovine preimplantation embryos exhibit VIP receptors, providing a basis for a receptor-mediated influence of VIP in the hatching of ovine blastocysts. PMID- 11194561 TI - Tumour necrosis factor alpha up-regulates matrix metalloproteinase-2 activity in periovulatory ovine follicles: metamorphic and endocrine implications. AB - The collagenous matrix of the wall of periovulatory follicles is degraded and remodelled during ovulatory ovarian rupture and luteinization. Matrix metalloproteinase-2 (MMP-2) belongs to a family of zinc endopeptidases that cleave extracellular proteins; its primary substrate is the type IV collagen of basement membranes. Tumour necrosis factor alpha (TNFalpha) is a putative mediator of collagenolysis and ovulation. The objective of this investigation was to ascertain the regulatory role of TNFalpha on MMP-2 activity relevant to the folliculo-luteal transition in ewes. Luteal regression and the preovulatory surge of gonadotropins were induced by administration of prostaglandin F2alpha and gonadotropin-releasing hormone (GnRH) on Days 14 and 15.5 (= 0 h) of the oestrous cycle, respectively. Ovulation occurs from the dominant follicle approximately 24 h after GnRH. An immunocapture-activity assay was used to measure MMP-2 in follicular extracts. Bioactive MMP-2 increased from 0 to 20 to 40 h after GnRH. Enzyme was immunolocalized at 40 h to the connective tissue framework that invades the parenchyma of the formative corpus luteum. Activity of MMP-2 was up regulated by incubation (20 h) of 0-h follicular explants with TNFalpha; this response was suppressed by the transcriptional inhibitor actinomycin D. Activity of MMP-2 was reduced when preovulatory follicular tissues were incubated (12-h explants for 6 h) with TNFalpha antiserum. Ovulation was blocked by intrafollicular injection of TNFalpha antiserum. Unruptured follicles luteinized, but were deficient in collagenous/vascularized trabeculae, and produced less progesterone than their control luteal counterparts. It is suggested that TNFalpha, via MMP-2 induction, contributes to the reorganization of an ovulatory follicle into a fully competent corpus luteum. PMID- 11194562 TI - Contraceptive effects of levonorgestrel implants in a marsupial. AB - The effect of subcutaneous levonorgestrel implants on reproduction in female tammar wallabies was investigated during the breeding and non-breeding season. Female tammars were given either a control or a levonorgestrel implant and their pouch young were removed to terminate embryonic diapause. Both the control and the levonorgestrel-implant animals treated during the months of May and June gave birth, demonstrating that levonorgestrel does not prevent the reactivation of the diapausing blastocyst or its subsequent development when given at these times. However, none of the levonorgestrel-treated animals mated post partum, whereas all of the control females that gave birth had a post partum oestrus and mated. Control animals gave birth again when the neonate was removed, and continued to breed normally during the following 36 months of the investigation. None of the levonorgestrel-treated animals gave birth again or mated during the next 36 months. Animals given control implants during December did not reactivate or give birth until the normal start of the breeding season in late January. Animals treated with levonorgestrel implants during December did not reactivate with the control animals at the beginning of the breeding season and did not give birth during the next 36 months. There were no effects of levonorgestrel treatment on early lactation. Levonorgestrel implants were removed from six females and four of these animals resumed reproductive activity, confirming that the contraceptive effect of the implants is reversible. Levonorgestrel implants therefore provide a highly effective, reversible and long-term method of contraception for tammar wallabies. This contraceptive system appears to offer a method of population control for the management of overabundant captive and selected wild populations of macropodid marsupials. PMID- 11194563 TI - Fetal organ growth in response to oesophageal infusion of amniotic fluid, colostrum, milk or gastrin-releasing peptide: a study in fetal sheep. AB - The hypothesis of the present study was that the infusion of the biological fluids to which the developing gut is normally exposed (i.e. amniotic fluid, colostrum, milk) and a single growth factor (gastrin-releasing peptide), which is found in high concentrations in fetal fluids and milk, could ameliorate the altered growth induced by the elimination of swallowed input secondary to ligation of the oesophagus. At 108-110 days of gestation the fetal oesophagus was ligated and a catheter inserted towards the stomach (32 fetuses). At 117-119 days of gestation saline (n = 5), amniotic fluid (n = 5), colostral whey (n = 5), milk whey (n = 5) or gastrin-releasing peptide (3.6 nmol day(-1), n = 6), was infused for 7 days (4 x 20 mL day(-1)), or no infusion was given (ligated group, n = 6). A further 15 fetuses were not ligated (normal group, n = 15). All fetuses had carotid artery and/or jugular vein catheters implanted. At 124-126 days of gestation the fetus was delivered and fetal body and organ weights recorded. Analysing the results by ANOVA, there were no effects of either ligation alone or infusion after ligation on fetal weight, crown-rump length, or weight relative to bodyweight of heart, adrenal, pancreas, large intestine and cecum. There were significant differences between the infusion groups for lungs, kidney, pancreas, total gut, abomasum, small intestine, spleen, chest and neck thymus, and mesenteric lymph nodes. Ligation alone significantly reduced small intestinal growth and increased kidney and spleen growth. Colostrum infusion enhanced growth of most organs. Gastrin-releasing peptide significantly increased growth of all the immune organs studied. It was concluded that at an age when premature delivery could be encountered, the fetal gut is capable of significant adaptive growth, to varying degrees, depending on the enteral diet. Growth effects in organs distant to the gut suggest that either gastrointestinal uptake and transport of growth factors or altered nutrient uptake and/or availability can affect the growth of other major fetal organs. PMID- 11194564 TI - Maternal copper supplementation protects the neonatal rat lung against the adverse effects of maternal nicotine exposure. AB - Maternal nicotine exposure interferes with the extracellular formation of the connective tissue framework of the neonatal lung, a process that is dependent on copper-dependent lysyl oxidase. It has been shown that, during the phase of lung development associated with alveolarization, maternal nicotine exposure resulted in a reduction in the copper content and thus conceivably in the activity of lysyl oxidase of the neonatal lung. Therefore the aims of this study were (a) to determine the effects of maternal nicotine exposure during gestation and lactation on neonatal lung development, and (b) to establish whether maternal copper supplementation during gestation and lactation prevented the effect of maternal nicotine exposure on neonatal lung development. Pregnant rats were randomly divided into four groups: the control group received saline; the second group received 1 mg nicotine (kg bodyweight)(-1) day(-1) subcutaneously; the third group received 1 mg copper (kg bodyweight)(-1) day(-1); and the fourth group received both nicotine and copper in the same quantities as the previous two groups. Lung tissue of 14- and 42-day-old rat pups were processed for light microscopy. Maternal nicotine exposure during gestation and lactation resulted in (a) decreased alveolar number, (b) reduced internal surface area and (c) increased alveolar volume. Copper supplementation during gestation and lactation prevented the adverse effects of maternal nicotine exposure during gestation and lactation on the development of the alveolar region of the rat lung. PMID- 11194565 TI - NMR-based screening in drug discovery. PMID- 11194566 TI - Biophysical and biochemical investigations of RNA catalysis in the hammerhead ribozyme. PMID- 11194567 TI - Recent advances in the understanding of membrane protein assembly and structure. PMID- 11194568 TI - Prion propagation and molecular chaperones. PMID- 11194569 TI - Physicians' legal duties regarding the use of genetic tests to predict and diagnose Alzheimer disease. PMID- 11194570 TI - The physician profile database. Publishing malpractice information on the Internet. PMID- 11194571 TI - Regulation of medical devices in the European Union. PMID- 11194572 TI - To know or not to know. Legal perspectives on genetic privacy and disclosure of an individual's genetic profile. PMID- 11194573 TI - Asymptomatic rise in transaminase levels: clinician's dilemma and patient's concern. PMID- 11194574 TI - Iatrogenic hepatotoxicity. PMID- 11194575 TI - Gastroenterology and the Internet. AB - BACKGROUND: The Internet has come to play a significant role in health care across the world. Simple specific how-to-use information about the Internet for Gastroenterologists is lacking in the literature. AIM: To explain the origin, functions, use and impact of the Internet and to provide a list of important web site addresses related to Gastroenterology. METHODS: We undertook a detailed scan of the Internet and identified a large number of web sites pertaining to Gastroenterology. The sites were then thoroughly searched to evaluate their potential usefulness to Gastroenterology clinicians and researchers. A list of web site addresses were then compiled according to specific sub-areas of Gastroenterology. CONCLUSION: This overview of Internet and compliation of important web site addresses is expected to stimulate and instruct Gastroenterologists in the use of the Net in health care delivery and research. The list of web sites according to subspecialities provided in this article is expected to facilitate their search. PMID- 11194576 TI - Portal system thrombosis: a new dimension of high altitude illnesses. PMID- 11194577 TI - Effect of Giardia lamblia on duodenal disaccharidase levels in humans. AB - The study was conducted to detect the effect of giardiasis on human disaccharidase levels. Forty patients attending the medical outpatient department of PGIMER, Chandigarh were enrolled. Twenty patients, positive for Giardia lamblia comprised the study group while 20 patients negative for Giardia lamblia were taken as controls. Upper gastrointestinal endoscopy was performed in all patients. Estimation of lactase, sucrase, maltase and trehalase was done in biopsies. Histopathological investigation was carried out in all biopsy specimens after Haematoxylin and Eosin staining. Complaints of pain abdomen and bloating occurred commonly in giardiasis. Four biopsy samples in study group showed mild increase in lymphomononuclear infiltrate. Giardia lamblia was detected in 7 biopsies. Lactase levels were decreased significantly (p < 0.05) in giardiasis. Rest of the enzymes were comparable to the controls. No differences in the enzyme activities were observed between males and females in either group and with the duration of symptoms. PMID- 11194578 TI - Evaluation of garlic oil as a contact dissolution agent for gallstones: comparison with monooctanoin. AB - AIM: To find a better contact solvent to dissolve gallstones we studied invitro use of garlic oil and compared it with monooctanoin. METHODS: In the first stage gall stones obtained from patients after cholecystectomy were subjected to dissolution in different concentrations of garlic oil. Then the rate of dissolution of gall stones in garlic oil was compared to that in monooctanoin in stage II. Efficacy of various concentration of garlic oil and monoocatanoin in dissolving gallstones in artificial gall bladder and common bile duct models were compared in stage III. RESULTS: Garlic oil dissolved the cholesterol gall stones in proportion to the concentration used. The gall stone fragmentation was faster [6 hours V/s 36 hours] and more [88.30% V/s 71.01%] by garlic oil in comparison to monooctanoin in test tubes and even in artificial gallbladder and common bile duct models. CONCLUSIONS: Garlic oil is a better contact dissolving agent of gallstones than monooctanoin. PMID- 11194579 TI - Gastric tuberculosis presenting as non-healing ulcer: case report. AB - Tuberculous infection of the stomach is uncommon and the diagnosis is often missed due to its non-specific presentation. We report a case of gastric tuberculosis which presented as a non-healing gastric ulcer. PMID- 11194580 TI - Angiographic detection and embolization of a Dieulafoy's lesion. PMID- 11194581 TI - Non-traumatic tracheoesophageal fistula in an adult. PMID- 11194582 TI - Primary malignant melanoma of the oesophagus: case report and review. AB - Primary malignant melanoma of the oesophagus [PMME] is a rare tumour. Worldwide, less than 200 cases have been reported to date. We report here a 72 year-old Saudi male who presented with abdominal pain and anorexia. On endoscopy a dark lesion was found in the oesophagus. Its histopathological features were consistent with malignant melanoma. There were no other melanotic lesions elsewhere. PMME occurs most frequently in the 7th and 8th decades of life with a male predominance. It is an aggressive tumour with the majority of patients dying in less than 2 years due to metastases to vital organs. Surgery is the treatment of choice. However, radiation may be useful as adjuvant therapy. PMID- 11194583 TI - Diffuse hepatic hemangiomatosis: case report. AB - Hemangiomas of the liver are often incidental findings on routine abdominal ultrasonography. Majority are single and asymptomatic. We report a patient with diffuse hemangiomatosis of the liver who presented with thrombocytopenia and congestive cardiac failure. PMID- 11194584 TI - Spontaneous neonatal gall bladder perforation. AB - A full term neonate was operated for diaphragmatic eventration through the chest. Postoperatively the baby developed gastric outlet obstruction. Ultrasonography and barium meal examination were suggestive of extrinsic compression in the region of the pylorus. At laparotomy a gall bladder perforation was found producing a biloma just abve the pylorus. Drainage of the bilioma and temporary cholecystostomy cured the gastric outlet obstruction. PMID- 11194585 TI - Infantile gastric teratoma. AB - Gastric teratoma is a rare tumour, comprising less than 1% of all teratomas in children. A 5 month old male child, who presented with an abdominal mass, fever and vomiting was diagnosed to have a gastric teratoma on ultrasonography, CT scan and serum alpha-feto protein. Complete excision of the tumour was performed. No chemotherapy was given. The histological examination revealed immature teratoma. The child is well 1 year after surgery. PMID- 11194586 TI - Hepatocyte isolation and transplantation in syngenic rats. AB - Refinement of techniques to isolate viable hepatocytes began in the late 1960's. It was established that perfusion of the intact liver as opposed to incubation of liver slices or chopped tissue increased the yield of cells. The present study aims to establish a simple, two-step, collagenase digestion method for hepatocyte isolation. A single inbred Fisher rat was used for hepatocyte isolation. The liver was perfused in-situ with perfusion buffer containing ethylene glycol bis N, N1, tetra acetic acid (EGTA), followed by the collagenase buffer. The liver was excised and gently minced. The tissue was resuspended in the collagenase buffer to complete dissociation. The cell suspension obtained was washed, centrifuged and filtered to complete the isolation procedure. The trypan blue exclusion test showed 80-85% cell viability. The isolated cells were transplanted into the splenic parenchyma of syngenic rats. Survival of the transplanted hepatocytes was confirmed by histological examination at the end of 90 days. This two step technique of in-situ liver perfusion gives a high yield of viable hepatocytes which show long term survival after transplantation. PMID- 11194587 TI - Review of a hospital experience of enterocutaneous fistula. AB - A retrospective analysis of records of 46 patients with enterocutaneous fistulas treated over a period of three and half years has been done. There were 28 males and 18 females, with 80% of patients being in age group of 25-35 years. Forty five patients were postoperative and in one patient fistula occurred spontaneously. Tuberculosis was the most common underlying pathology, seen in 32.6% followed by enteric fever in 23.9%. The small intestine was the most common site for the origin of fistula, seen in 34 patients (73.9%). There were 22 patients with high output fistula and 24 with low output. For high output fistulas, enteric fever was the most common cause (45%) and ileum was the most site of origin (82%). Low output fistulas were mainly of tubercular aetiology (62%) and involved ileum in 62% of cases. Nineteen out of 22 patients of high output fistulae had sepsis. Fourteen of these had generalised peritonitis (63%) and 5 had localized intra-abdominal collections (27%). Spontaneous closure occurred in 45.6% of patients on conservative management and 37% patients underwent surgical intervention. The overall mortality was 30.4%. High output fistulae had mortality figure of 54.5% and low output fistulas 8.4%. Mortality in relation to sepsis was 63%. No patient with sepsis and without surgical intervention survived. Following surgical intervention mortality was 50% in patients who showed evidence of sepsis. Early and effective control of sepsis is the most important factor determining outcome in patients of enterocutaneous fistula. PMID- 11194588 TI - Ruptured liver abscess with fulminant amoebic colitis: case report with review. AB - Amoebic liver abscess is the commonest extra intestinal manifestation of amoebiasis. Intraperitoneal rupture of liver abscess and fulminant necrotizing amoebic colitis are rare occurrences which complicate a severe form of invasive disease caused by Entamoeba histolytica. These complications are associated with a high morbidity and mortality. Synchronous pathological lesions in colon and liver are rare. Still rare is the occurrence of complicated colonic and hepatic invasive amoebiasis presenting as an acute abdomen. One such presentation of ruptured liver abscess and necrotizing amoebic colitis in a 70 year old male which was successfully managed is being reported. PMID- 11194589 TI - Oesophageal leiomyoma presenting as a mediastinal mass. AB - A 28 year old male presented with complaints of retrosternal pain, discomfort and dysphagia of 4 years duration. Barium swallow and oesophagoscopy were suggestive of extrinsic compression of thoracic oesophagus. CT scan of chest was suggestive of a large mediastinal lymph node mass. Thoracotomy and open biopsy showed a benign mesenchymal tumor on frozen section. A transthoracic oesophagectomy with gastric pull up and cervical oesophago-gastric anastomosis was performed. The postoperative course was uneventful and the patient discharged on the tenth postoperative day. PMID- 11194590 TI - Primary omental torsion: case report. AB - Primary omental torsion is a rare condition. It is confused with acute appendicitis. Presence of a normal appendix at surgery should raise the suspicion of omental torsion. PMID- 11194591 TI - Post cholecystectomy Mirizzi syndrome? PMID- 11194592 TI - Pacing in heart failure: improved ventricular interaction in diastole rather than systolic re-synchronization. AB - AIMS: To determine the mechanism by which left ventricular and biventricular pacing works. BACKGROUND: Pacing for congestive heart failure patients is employed in those with left bundle branch block on the basis that it will improve discoordinated contraction; however, the response is unpredictable. The authors propose that the mechanism of benefit is rather related to improvement of ventricular interaction in diastole (VID). VID is found in patients with a high left ventricular end-diastolic pressure (> 15 mmHg). Left ventricular pacing in these patients will delay right ventricular filling and allow greater left ventricular filling before the onset of VID. METHODS: The study group consisted of 18 congestive heart failure patients with an ejection fraction < 30% and with no more than Grade 1 mitral regurgitation. Group I comprised 10 patients with pulmonary capillary wedge pressure > 15 mmHg, four patients had a normal QRS duration and six had left bundle branch block. Group II comprised eight patients with pulmonary capillary wedge pressure < 15 mmHg, of whom five had a normal QRS duration. Haemodynamics were measured at baseline and during VDD pacing from either the left ventricle or right ventricle. RESULTS: The ratio of stroke volume/pulmonary capillary wedge pressure was calculated as an index of the relationship between left ventricular end-diastolic pressure and contractile function. This ratio was lower in group I than in group II patients (P = 0.005). In group I, haemodynamics were improved with left ventricular pacing (stroke volume/pulmonary capillary wedge pressure increased from 2.2 +/- 0.9 to 4.4 +/- 3.6, P = 0.03). In group II there was no response to either left ventricular or right ventricular pacing. The improvement with left ventricular pacing was unrelated to QRS duration (r = 0.09). CONCLUSIONS: Left ventricular pacing acutely benefits congestive heart failure patients with pulmonary capillary wedge pressure > 15 mmHg irrespective of left bundle branch block. The present data suggest that the mechanism of response may be an improvement in left ventricular filling rather than ventricular systolic re-synchronization. PMID- 11194593 TI - Rate dependence of the effect of antiarrhythmic drugs delaying cardiac repolarization: an overview. AB - Prolongation of the cardiac action potential and refractoriness (class III effect) is a potentially beneficial electrophysiological mechanism of action. However, this effect may be diminished or eliminated at rapid heart rates, so called 'reverse rate dependence' of prolongation of repolarization. Action potential duration normally shortens as heart rate increases, due to increases in outward repolarizing currents, and/or decreases in inward depolarizing currents. The assessment of the effect of drugs on action potential duration is complicated by inter-species differences in ionic currents mediating repolarization, heterogeneity within the heart in repolarizing currents, and differential effect of drugs in different species, during differing experimental conditions, and at different rates of stimulation. In general, most drugs which predominantly block the IKr repolarizing current exhibit reverse rate-dependent effects on cardiac repolarization. Drugs or combinations of drugs which produce multiple ionic channel blocks and possibly those which block the IKs current, may be less prone to this potentially undesirable effect. PMID- 11194594 TI - Efficacy and tolerability of continuous overdrive atrial pacing in atrial fibrillation. AB - Overdrive right atrial pacing has been used to prevent atrial fibrillation, but its efficacy in atrial fibrillation prevention and the patient tolerability and quality of life during high rate pacing remain uncertain. The objective of this study was to test the effects of a consistent atrial pacing algorithm that automatically paced the atrium at 30 ms shorter than the sinus P-P interval for atrial fibrillation prevention. Fifteen patients with sick sinus syndrome implanted with a Thera DR (model 7940 or 7960, Medtronic Inc.) were randomly programmed to rate adaptive dual chamber pacing (DDDR) or DDDR + consistent atrial pacing mode, each for an 8-week study period. The efficacy of consistent atrial pacing was assessed by the number of automatic mode switching and the number of premature atrial complexes. Symptoms and quality of life were assessed by the SF-36 quality of life questionnaire and an atrial fibrillation symptom checklist. The percentage of atrial pacing increased from 57 +/- 32% to 86 +/- 28%. Overall, there was no significant difference in the number of automatic mode switching episodes between DDDR and DDDR + consistent atrial pacing (47 +/- 90 vs 42 +/- 87, P > 0.05), but a significant reduction in premature atrial complexes by 74.7% (P < 0.001). There was no undue increase in atrial rate by the DDDR + consistent atrial pacing mode versus DDDR (63 +/- 13 vs 70 +/- 7 bpm). There was no significant difference in quality of life scores and symptom severity on frequency between the two modes of pacing, but a trend towards a lower frequency of symptoms in the DDDR + consistent atrial pacing mode compared with baseline (29.5 +/- 10.2 vs 25.1 +/- 9.7, P = 0.07). An algorithm that provides consistent atrial overdrive pacing can suppress atrial fibrillation triggering premature atrial complexes without the need to increase the overall atrial rate compared with conventional pacing. The algorithm appears to be well-tolerated, but further studies are needed to address the clinical impact of this atrial fibrillation prevention algorithm. PMID- 11194595 TI - New onset atrial flutter termination by overdrive transoesophageal pacing: effects of different protocols of stimulation. AB - AIM: We evaluated the effect of different stimulation protocols on atrial flutter interruption by transoesophageal pacing. METHODS AND RESULTS: Eighty patients with new onset atrial flutter were randomized into four groups. Pacing was attempted under the following conditions: with short bursts (5 s), without treatment (group A) and after oral administration of propafenone 600 mg (group B); with prolonged bursts (30 s), without treatment (group C) and after oral administration of propafenone 600 mg (group D). Pacing interrupted atrial flutter in 20% of patients in A, 55% in B, 50% in C and 85% in D. The use of longer bursts gave better results both in patients without treatment (P < 0.05: C vs A) and in patients with propafenone (P < 0.05: D vs B). Comparing groups with the same stimulation protocol, we observed a better response in patients treated with propafenone (P < 0.05: B vs A and D vs C). In the groups without treatment the use of shorter bursts was associated with a lower induction of stable atrial fibrillation (three vs nine episodes), in the groups on propafenone no differences were observed (one vs one episode). CONCLUSIONS: We conclude that the association of propafenone with long bursts gives the best result for interruption of new onset atrial flutter by transoesophageal pacing. PMID- 11194596 TI - Long-term evaluation of autonomic tone in patients below 50 years of age with unexplained cerebral infarction: relation to atrial vulnerability. AB - Preliminary studies have described, in young patients with unexplained cerebral infarction, electrophysiological abnormalities similar to those observed in paroxysmal atrial fibrillation. Moreover, in young adults with 'normal' hearts, increased susceptibility to paroxysmal atrial fibrillation with autonomic abnormalities as assessed by heart rate variability analysis have been reported. METHODS: The long-term time and frequency domain measures of heart rate variability were analysed prospectively from 24-h Holter ECG recordings in 25 patients (39 +/- 8 years) with unexplained cerebral infarction, and in 25 age-, sex- and cigarette-smoking-matched healthy control subjects. The day following the Holter ECG recordings, 9 +/- 4 months (mean) after the stroke, stroke patients underwent an electrophysiological study in order to analyse the electrical characteristics of their right atria and also to determine their vulnerability to atrial fibrillation. The correlations between autonomic tone parameters and electrophysiological findings were therefore assessed with linear regression analyses. RESULTS: All the measured components of heart rate variability either in time (SDNN, pNN50, SDANN/5, rMSSD) or frequency domains (total power, low-frequency, high-frequency power, low-frequency/high-frequency power ratio) were similar between stroke patients and controls. During electrophysiological study, atrial fibrillation was induced in 80% of stroke patients. Among these patients, atrial refractory periods were significantly shorter, local electrograms were longer, and latent atrial vulnerability index was markedly decreased when compared with patients having no inducible atrial fibrillation. Concerning heart rate variability analysis, no difference was found between patients with induced atrial fibrillation when compared with a matched subgroup of healthy control subjects. Furthermore, there was no statistically linear correlation between any of the measured autonomic tone parameters and any of the discovered atrial vulnerability markers. CONCLUSIONS: The long-term autonomic tone parameters of young patients presenting with a history of unexplained cerebral infarction are similar to those of healthy control subjects and are not correlated with atrial vulnerability parameters or atrial fibrillation inducibility. PMID- 11194597 TI - Electrophysiological determinants of atrial fibrillation in sinus node dysfunction despite atrial pacing. AB - AIMS: The effectiveness of atrial pacing in reducing the incidence of atrial fibrillation in patients with sinus node dysfunction is incomplete, and the correlation between electrophysiological atrial properties and the effect of permanent atrial pacing has been poorly investigated. Accordingly, the aim of the present study was to correlate electrophysiological data, in terms of atrial refractoriness, conduction parameters, and propensity to atrial fibrillation induction, and the likelihood of atrial fibrillation after DDD device implantation. METHODS AND RESULTS: The authors reviewed electrophysiological data of 41 patients with sinus node dysfunction (mean age 70 +/- 8 years, who were investigated free of anti-arrhythmic treatments before pacemaker implantation. At a drive cycle length of 600 ms, effective and functional refractory periods, S1 A1 and S2-A2 latency, A1 and A2 width, and latent vulnerability index (effective refractory period [ERP] A2), were measured. Atrial fibrillation induction was tested with up to three extrastimuli in 34 patients. Induction of sustained atrial fibrillation (> 1 min) was considered as the end-point. P-wave duration on the surface ECG in lead II/V1 was also measured. Minimal atrial rate was programmed between 60 and 75 bpm (mean: 64 +/- 4 bpm). After implantation, the patients were followed-up for 28 +/- 17 months, and ECG-documented occurrence of atrial fibrillation was determined. Electrophysiological characteristics of patients with (n = 12) or without (n = 29) paroxysmal atrial fibrillation before implantation were similar. When comparing patients with (n = 11) or without (n = 30) post-pacing atrial fibrillation occurrence, no differences were found in age, underlying heart disease, left atrial size, minimal pacing rate, and follow-up duration. Additionally, between the two former groups, there was no significant difference in terms of effective refractory periods (233 +/- 47 ms vs 239 +/- 25 ms), functional refractory periods (280 +/- 48 ms vs 272 +/- 21 ms), S1-A1 (44 +/ 20 ms vs 37 +/- 13 ms) and S2-A2 latency (77 +/- 28 ms vs 66 +/- 22 ms), and A1 duration (60 +/- 23 ms vs 53 +/- 16 ms). In contrast, in patients with post pacing atrial fibrillation occurrence, the P wave was more prolonged (116 +/- 22 ms vs 98 +/- 13 ms; P < 0.01), A2 was longer (116 +/- 41 ms vs 87 +/- 27 ms; P < 0.01), effective refractory periods/A2 was lower (2.1 +/- 0.4 cm vs 3.1 +/- 1.4 cm; P < 0.05), and rate of atrial fibrillation induction was higher (8/11 patients vs 8/23 patients; P < 0.05). Electrophysiological characteristics of patients free of post-pacing atrial fibrillation with associated (n = 6) or unassociated (n = 24) paroxysmal atrial fibrillation history before implantation were quite similar. In patients with post-pacing atrial fibrillation with associated (n = 6) or unassociated atrial fibrillation history (n = 5) before implantation, effective refractory periods was statistically different (207 +/- 23 ms vs 264 +/- 46 ms; P < 0.05). Values of effective refractory periods < 220 ms were significantly more frequent in patients with post-pacing atrial fibrillation than in patients without (4/11 patients vs 2/30 patients; P < 0.05). When comparing patients with post-pacing atrial fibrillation with effective refractory periods > or = 220 ms (n = 7) and < 220 ms (n = 4), A2 duration was remarkably prolonged (145 +/- 42 ms vs 90 +/- 11 ms; P < 0.05) in those with effective refractory periods > or = 220 ms. By contrast, between the two groups, effective refractory periods/A2 were identical (2.08 +/- 0.6 cm vs 2.15 +/- 0.3 cm; P = n.s.). CONCLUSION: Prolonged atrial refractoriness, lesser degrees of conduction disturbance and a lower rate of atrial fibrillation induction seem to be predictive of stable sinus rhythm. In contrast, patients with persistence of atrial fibrillation despite pacing have a more abnormal and inhomogeneous atrial substrate, as well as a higher rate of atrial fibrillation induction. Prolonged P wave, shortened refractoriness, or remarkably abnormal conduction disturbances in the presence of prolonged refractoriness limit the effectiveness of standard atrial pacing in atrial fibrillation prevention. Identification of predictive criteria of failure of single-site atrial pacing may be used to consider dual site atrial pacing in such patients with sinus node dysfunction. PMID- 11194598 TI - Recording monophasic action potentials using a platinum-electrode ablation catheter. AB - AIMS: The monophasic action potential (MAP) is conventionally recorded using Ag AgCl electrodes which are not suitable for delivering radiofrequency currents. To be able to use the sharp MAP upstroke for identifying the local activation, as a step towards the development of a MAP-guided catheter ablation technique, the possibility of recording MAP via platinum electrodes of an ordinary ablation catheter was explored. METHODS AND RESULTS: One hundred and forty-two MAP recordings from the endocardium were obtained via an ablation catheter in 40 patients undergoing electrophysiological study/catheter ablation. During sinus rhythm and pacing, 90% of the ventricular and 100% of the atrial MAPs had stable baselines. The amplitudes were 13 +/- 4.2 mV for ventricular and 2.4 +/- 0.8 mV for atrial MAPs. During mapping and ablation, MAPs and uni- and bipolar electrograms were recorded simultaneously using the same tip electrode in eight patients. The MAPs provided more distinct local activation than the electrograms. During 17 MAP recordings, additional MAPs were recorded simultaneously using an Ag-AgCl electrode catheter in the immediate vicinity of the ablation catheter. The MAPs taken with the ablation catheter had characteristics consistent with those taken with the Ag-AgCl catheter. CONCLUSIONS: (1) Platinum electrodes can be used for timely recording of MAPs in patients. (2) It is feasible to record MAPs and deliver radiofrequency currents via the same platinum-tip electrode. These findings suggest that MAP-guided catheter ablation is technically possible. PMID- 11194599 TI - Dose-related cardiac electrophysiological effects of intravenous magnesium. A double-blind placebo-controlled dose-response study in patients with paroxysmal supraventricular tachycardia. AB - AIMS: The role of magnesium as an antiarrhythmic drug is yet not conclusive. Therefore, we performed a double-blind, randomized, placebo-controlled dose response study of cardiac electrophysiological effects of intravenous magnesium. METHODS AND RESULTS: Thirty-six patients undergoing an electrophysiological evaluation for paroxysmal supraventricular tachycardia were randomized to one of the following dosages of intravenous magnesium (0, 5, 10 or 20 mmol). Conventional electrophysiological variables for sinus node function, atrial, atrioventricular node and ventricular conduction and refractoriness were measured before and after magnesium administration. Prolongation of the atrial-His interval was found at 5 mmol of magnesium compared with placebo and no further prolongation was observed at higher doses (-3 +/- 8, 11 +/- 9, 7 +/- 15, 11 +/- 16, for the dosages of 0, 5, 10 and 20 mmol of magnesium, respectively, P < 0.05). Measures of sinus node function, intra-atrial conduction and conduction through the Purkinje system were unaffected by magnesium. Male gender was associated with prolongation in atrial effective refractory period, in contrast to shortening in females: 2 +/- 43, 35 +/- 44, 36 +/- 33, 13 +/- 12 ms for males and 3 +/- 6, -12 +/- 11, -13 +/- 12, 0 +/- 23 ms for females, respectively (P < 0.001). CONCLUSION: Atrioventricular node conduction was prolonged by 5 mmol intravenous magnesium and no further prolongation was observed at higher dosages. At dosages of 5 and 10 mmol magnesium the atrial effective refractoriness was prolonged in males and shortened in females. PMID- 11194600 TI - Ventricular fibrillation induced by rapid atrial rates in patients with hypertrophic cardiomyopathy. AB - AIMS: To describe the mechanisms of induction of ventricular fibrillation (VF) by rapid atrial rates in patients with hypertrophic cardiomyopathy (HCM). METHODS: Electrophysiological studies, management and follow-up in three patients with HCM with VF induced by atrial pacing. RESULTS: In one patient, spontaneous sinus tachycardia triggered VF. In another patient, VF occurred after verapamil infusion during rapid atrial fibrillation, and in the remaining patient there was no clinical VF. In all three patients, short runs of atrial pacing (cycle length 272-380 ms) induced VF, and QRS widening preceded fibrillation in all patients. Marked ventricular electrogram fragmentation was documented in one patient during atrial pacing and in another patient during late ventricular extra-stimuli. Hypotension was associated with sinus tachycardia in one patient. The two patients developing clinical VF underwent atrioventricular (AV) junctional ablation; a ventricular defibrillator was implanted in one, and a mode-switching dual-chamber pacemaker in the other. No arrhythmic events occurred during 34- and 35-month follow-up, respectively. In the other patient, postatrial fibrillation pauses caused syncope, and he is asymptomatic 52 months after implantation of a dual-chamber pacemaker. CONCLUSIONS: Rapid atrial rates can trigger VF in some patients with HCM, probably through a combination of electrophysiological and ischaemic mechanisms. AV junctional ablation may prevent VF in selected cases. PMID- 11194601 TI - The effects of orthostasis on the ventricular-evoked response. AB - AIMS: The effects of orthostasis on the morphology of the ventricular-evoked response were investigated. METHODS AND RESULTS: Seven patients (five females; 74.9 +/- 4.6 years) with second- or third-degree atrioventricular block received DDD pacemakers Physios CTM 01 with fractal-coated ventricular leads (both Biotronik, Germany). At their 3-month follow-up sessions, these patients underwent tilt-table tests. Heart rate, mean arterial blood pressure and ventricular-evoked response were measured continuously. Signals were averaged over 15 consecutive beats. Coefficients of correlation between selected ventricular-evoked response parameters and heart rate or mean arterial blood pressure were calculated. Tilt upwards affected heart rate, mean arterial blood pressure and ventricular-evoked response extremes showed non-uniform, patient specific changes that were not related directly to other parameters. Heart rates significantly increased in six patients following tilt upwards. For all patients, ventricular-evoked response plateau amplitudes immediately increased with tilt upwards. Furthermore, repolarization times correlated with changes in heart rates (r = -0.78). CONCLUSIONS: Monitoring of the ventricular-evoked response during tilt-table testing revealed that the plateau amplitude of the ventricular-evoked response depends on the patient's position; ventricular-evoked response increased in the upright position and decreased in the supine position. Furthermore, repolarization time and heart rate correlated inversely; higher heart rates resulted in a shortening of the ventricular-evoked response. PMID- 11194602 TI - 'The Italian Protocol': a simplified head-up tilt testing potentiated with oral nitroglycerin to assess patients with unexplained syncope. AB - Head-up tilt testing potentiated by sublingual nitroglycerin (NTG), advocated by an Italian group, is a simple and safe but still not a standardized, diagnostic tool for the investigation of syncope. In fact, owing to its rapid spread, the original protocol received, often arbitrarily, many subsequent modifications. We now define the best methodology of the test on strictly evidence-based criteria as: stabilization phase of 5 min in the supine position; passive phase of 20 min at a tilt angle of 60 degrees; provocation phase of further 15 min after 400 micrograms NTG sublingual spray. Test interruption is made when the protocol is completed in the absence of symptoms, or there is occurrence of syncope, or occurrence of progressive (> 5 min) orthostatic hypotension. We intend that this protocol, named by us as 'The Italian Protocol', will be accepted as the standard methodology of the tilt test potentiated by sublingual nitrates. PMID- 11194603 TI - Venous pooling during nitrate-stimulated tilt testing in patients with vasovagal syncope. AB - AIMS: To investigate the importance of venous pooling and variation in venous tone during nitrate-stimulated tilt testing in patients. METHODS: Ten patients with a history of vasovagal syncope underwent an upright tilt test after an injection of 99mTc-labelled albumin. A gamma camera was positioned at the level of the lower legs. The patients were tilted to 90 degrees for 30 min or until symptoms developed. In those subjects who did not show any symptoms before the end of the 30-min period, isosorbide dinitrate (ISDN) 5 mg was given sublingually and the test was prolonged for a maximum of 15 min. RESULTS: Nine of 10 patients needed nitrate stimulation to develop symptoms, and one patient remained symptom free following ISDN administration. Measurement of radioactivity revealed no significant increase in calf volume after nitrate stimulation (the mean volume increase was 77% before ISDN stimulation and a further 0.9% afterwards). CONCLUSIONS: The higher sensitivity for vasovagal syncope during upright tilt testing after administration of sublingual ISDN is not due to an increase in venous pooling in the lower extremities. PMID- 11194604 TI - Prevention of recurrent ventricular fibrillation by ventricular rate stabilization. AB - This report describes a post-infarct patient with recurrent ventricular fibrillation in the absence of acute ischaemia, in whom arrhythmia recurrences could be prevented by ventricular rate stabilization of a third-generation cardioverter defibrillator. Review of the literature and clinical implications are discussed. PMID- 11194605 TI - Ablation of idiopathic ventricular tachycardia by bipolar radiofrequency current application between the left aortic sinus and the left ventricle. AB - BACKGROUND: Failure to ablate idiopathic ventricular outflow tract tachycardia by radiofrequency current is not uncommon and suggests that non-standard approaches may be required to map and suppress idiopathic ventricular tachyarrhythmias in some patients. METHODS AND RESULTS: Left and right ventricular activation and pace mapping proved inadequate for radiofrequency application in a patient with idiopathic ventricular outflow tract tachycardia. Presystolic activity was recorded at the left aortic sinus of Valsalva, and the QRS complex recorded at this location during pacing showed few differences compared with that recorded during tachycardia. Radiofrequency current application at this site transiently suppressed the tachycardia. Following new mapping of the left ventricle outflow tract, radiofrequency application just below the aortic valve in close proximity to the previous aortic application site transiently abolished the arrhythmia. Finally, bipolar radiofrequency application between the distal electrode of the aortic catheter and the distal electrode of a second catheter placed in the left ventricular subaortic area permanently suppressed the tachycardia. CONCLUSION: Bipolar radiofrequency application between the aortic sinus of Valsalva and the left ventricle could be an alternative approach in occasional patients with idiopathic ventricular outflow tract tachycardia resistant to conventional left ventricular and aortic root unipolar radiofrequency application. PMID- 11194606 TI - 2000, Future of Arrhythmology: Lessons from the Past, Promises for Tomorrow. Maastricht, The Netheralands, 15-18 April 2000. Abstracts. PMID- 11194607 TI - Anterior cruciate ligament reconstruction with the Leeds-Keio artificial ligament. AB - The Leeds-Keio (L-K) artificial ligament, developed for knee ligament reconstruction, is made of polyester with a maximum tensile strength of 2200 N. This implant works not only as a ligament but also as a scaffold onto which natural tissue grows from synovium. In an animal experiment, each strand of the L K ligament was covered with new tissue by 2-3 weeks after anterior cruciate ligament reconstruction. Eight weeks postoperatively, abundant fibrous tissue with extensive vascularity covered the implant, which was still histologically immature. After 16 weeks, vascularization and tissue induction began to subside, and histologic analysis showed dense fibers running longitudinally and parallel. By 36 weeks, the new ligament looked like a natural anterior cruciate ligament, although histologically more cells could be seen than in the natural ligament. This maturation was observed only when the substitute was implanted under good tension. Clinically, the surgical procedure has been improved over the past 10 years, to the current practice in which the tape-in-tube double L-K ligament employs a small piece of autogenous tissue to promote early tissue induction and maturation. Using this practice (n = 135), more than 85% of the patients were satisfied subjectively, objectively, and arthroscopically at the 5-year postoperative FU period. Few patients had joint effusion postoperatively. Sacrifice of autogenous tissue is minimal. The patient can return to activities of daily living within 2 weeks, and more than 50% of them to sports within 10 weeks, and the new ligament is expected to keep its function for a long period as ingrowth completes the structure biologically. PMID- 11194608 TI - Clinical application of artificial ligament for ankle instability--long-term follow-up. AB - We have applied a reconstructive operation to patients with injury of the lateral ligament in the ankle joint using an artificial ligament made of polyester (Leeds Keio) since 1985. The operation was performed on 451 feet of 436 patients. Average follow-up period was 5 years and 8 months. Talar tilt and anterior drawer translation before and after the operation were improved from 16 degrees to 4 degrees and from 11 mm to 4 mm, respectively. In this study, which has followed the same patients over an extended period, there were no cases with a decrease in the range of motion of the joint, with further development of osteoarthritis, or with a poorer result than those observed in our earlier study, which reported a short-term follow-up of the same patients. It may therefore be concluded that this reconstructive procedure of the lateral ligament of the ankle joint, using the artificial ligament, is also excellent after long-term follow-up. PMID- 11194609 TI - Long-term results of anterior cruciate ligament reconstruction using semitendinosus and gracilis tendons with Kennedy ligament augmentation device compared with patellar tendon autografts. AB - ACL reconstructions were postoperatively evaluated in 102 patients who underwent surgery using an arthroscopically assisted double-incision technique. Augmentation of the distally based semitendinosus and gracilis tendons was done either with the Kennedy ligament augmentation device (LAD) (Group 1 patients, mean follow-up of 108 months) or bone-patellar-tendon-bone graft (Group 2 patients, mean follow-up of 109 months). At follow-up, serial KT-1000 measurements showed < or = 5 mm side-to-side differences in 70% of Group 1 and 90% of Group 2 patients. No differences were found among patients regarding postreconstruction complications such as loss in motion range, patellofemoral crepitus, osteoarthritis, and muscle disfunction. PMID- 11194610 TI - Follow-up study of Gore-Tex artificial ligament--special emphasis on tunnel osteolysis. AB - The Gore-Tex anterior cruciate ligament has been implanted in 123 patients at our institutions between 1984 and 1993. The Gore-Tex ligaments were totally ruptured in 26 cases. In the remaining 97 cases, 80 were followed up 5-11 years after operation. Graft loosening occurred in half of the cases, and osteoarthritic change was developed in 62% of the cases. Moreover, tibial and tunnel osteolysis was observed in most of the cases. Judging from these follow-up results, the Gore Tex ligament should not be used for anterior cruciate ligament reconstruction. PMID- 11194611 TI - Tissue expander: histological and histochemical study 6 months after transplant- our experience. AB - Implanting an expander in the subcutaneous layer causes gradual expansion and provides additional tissue for reconstruction of tissular defects. The force applied remodels the connective tissue and modifies dermis contractibility in additional tissue. Other authors confirm that parameters such as mitosis and hyaluronan influence the system in the tissue regeneration processes. We studied histochemical and morphological variations of tissue expanders before and 6 months after transplant. Our histochemical data do not show any changes in dermis glycosaminoglycans of the expanded and transplant-expanded skin when compared to controls. Morphological data demonstrate reorganization of connective fibers and disappearance of the papillar layer. The latter is not yet formed in the expanded skin 6 months after transplant. This suggests that a long time is required for biological reconstruction of epidermal-dermal interactions after transplant. PMID- 11194612 TI - Biomechanical performance of silicone and latex external condom catheters. AB - Standard in vivo biomechanical performance tests and a pilot clinical study of latex external condom catheters (ECCs) and silicone ECCs demonstrated the superior performance of the silicone ECC over that of the latex ECC. The silicone ECC has a self-adhesive that binds more securely to human skin than the self adhesive of latex ECC. In addition, the moisture vapor transmission through silicone is significantly greater than through latex. The aggressive self adhesive of the silicone ECC significantly reduced ECC catheter pop-off compared to that of latex ECC. Silicone ECC removal can be facilitated by the application of a warm, wet cloth to the exterior surface of the silicone ECC, which significantly reduces its self-adhesive force. Constant, gentle traction is then applied to the silicone catheter outlet end to achieve atraumatic silicone ECC removal. On the basis of the results of these standardized tests and pilot study, the silicone ECC is recommended for incontinent men without obstructive uropathy. PMID- 11194613 TI - Routine practices and additional precautions for preventing the transmission of infection in health care. PMID- 11194614 TI - Infection prevention and control practices for personal services: tattoing, ear/body piercing, and electrolysis. PMID- 11194615 TI - Effect of seated posture on interface pressure in children who are able-bodied and who have myelomeningocele. AB - PURPOSE: The objective of this study was to investigate the relationship between sitting position and interface pressure distribution in seated children. METHOD: Fifteen able-bodied children and 15 children with myelomeningocele complete paraplegia, aged 7 to 18 years were included in the study. The body-seat interface pressure was measured with the QA pressure measurement system. Four sitting positions typically used to reduce body-seat interface pressure position (recline, tilt, combined and lean forward) were compared to a neutral position. RESULTS: Test/re-test Pearson correlation coefficients were greater than 0.94 for maximum pressure and greater than 0.88 for mean pressure at all test positions (p < 0.0001) and, for the risk area (defined as the percentage of sensors which recorded pressures greater than 40 mm Hg.) varied from 0.62 to 0.85 (p < 0.0005). Maximum pressures for the myelomeningocele group were significantly higher than those recorded for able-bodied subjects in the neutral, combined and lean forward positions (p < 0.001). For the able-bodied subjects, maximum pressures at the combined (p < 0.001), tilt (p < 0.05) and lean forward (p < 0.0001) positions were significantly lower than those measured at the neutral position. For the myelomeningocele subjects, maximum pressure at all tested positions was significantly lower than at the neutral position (p < 0.05). CONCLUSIONS: The results point to the importance of measuring body-seat interface pressure for each wheelchair user and of using the information to customize wheelchair utilization. PMID- 11194617 TI - How does spinal cord injury affect marital relationship? A story from both sides of the couple. AB - PURPOSE: To explore the impact of spinal cord injury (SCI) upon the family and marital relationship in Hong Kong. METHOD: Semi-structured interviews were conducted on 66 persons with SCI and 40 spouses. Qualitative information on family and marital relationships, life satisfaction, social functioning and leisure activities was transcribed and analysed. RESULTS AND CONCLUSION: It was found that the impact of the SCI was manifested in different but interrelated aspects onto the individuals and their spouses. However, many of the problems were due to the lack of communication between them. Rehabilitation professionals should then treat the couple as a single unit in order to facilitate mutual understanding and get rid of any distorted perception. PMID- 11194616 TI - A comparison of chronic pain patients and controls on traumatic events in childhood. AB - PURPOSE: The purpose was to examine the incidence of traumatic events in childhood, such as sexual and physical abuse, in a chronic pain group and a control group of hospital employees without chronic pain. METHOD: Ninety two patients with chronic pain, age range 20-62, were consecutively recruited from the outpatient clinics of a rehabilitation hospital and a general hospital. Ninety eight hospital employees, age range 20-62, were consecutively recruited from the employee health office of a rehabilitation hospital. All participants responded to nine questions related to sexual, physical and verbal abuse in childhood and completed the Childhood Traumatic Events Scale. A logistic regression with age, gender, sexual, physical, and verbal abuse, death of a family member, childhood illness, major upheaval before age 17, as independent variables were used to predict membership in the pain group contrasted with the control group. RESULTS: Child abuse was reported in the childhood history by 54.4% of the chronic pain group, compared with 21.4% of the control group. A logistic regression showed that after adjusting for gender and age, sexual and verbal abuse were statistically significant predictors of being a member of the pain group. Odds ratios were sexual abuse: 2.67, p < 0.05, CI 1.00-7.14. Verbal abuse: 4.39, p < 0.001, CI 1.93-9.97. A logistic regression was modelled to predict child abuse when gender was taken into account. The results of the logistic regression showed that pain was a significant predictor for sexual abuse after adjusting for gender and age: odds ratio 4.37, p < 0.001, CI 1.80-10.60. Gender was not a statistically significant predictor for sexual abuse, after adjusting for pain and age: odds ratio 2.92, p < 0.072, CI 0.91-9.42. CONCLUSIONS: A history of physical, sexual and verbal abuse is more likely to occur in a chronic pain group than in a control group of hospital employees. Although child abuse is reported to be as high as 25% in the general American population, the statistics for chronic pain patients are twice as high as in the general population. The mechanisms for abuse include age, gender, and early family environment. PMID- 11194618 TI - Disability, coping and quality of life in individuals with muscular dystrophy: a prospective study over five years. AB - PURPOSE: The present study investigates progressive muscular dystrophy over a five year period. The purpose is twofold: to describe changes over time and to investigate relations between disability, coping and quality of life. METHOD: The study group comprised 45 adults (16 men and 29 women), with an average age of 44 years. All were assessed in 1991 and 1996, with the following instruments: the ADL staircase, the Self-report ADL, the Mental Adjustment to Cancer scale, the Sickness Impact Profile and the Psychosocial well-being questionnaire (Kaasa). RESULTS: Increasing disability was accompanied by an increase in dependence on others and a significant deterioration of health-related quality of life and with regard to 'Satisfaction'. The predominant type of coping was 'Fighting spirit', whilst 'Fatalism' showed the greatest decline over time. 'Ambulation' and the ADL staircase correlated with 'Physical index' on the SIP. Correlations between disability, coping and quality of life were moderate. The results can serve as a basis for planning and evaluation of recurring rehabilitation for persons with MD. PMID- 11194619 TI - A comparison of the responsiveness of the Nottingham extended activities of daily living scale, London handicap scale and SF-36. AB - PURPOSE: Clinical trials require scales which are sensitive to the effects of intervention. This study examined the sensitivity to change of three generic health status measurement scales commonly used in evaluations of interventions in chronic, disabling disease. METHODS: Questionnaires comprising the SF-36, London Handicap Scale and Nottingham Extended Activities of Daily Living scale were administered to 81 patients before and after hip replacement. Changes were quantified as 'effect sizes'. RESULTS: Eighty nine per cent of patients reported improvements three months after surgery. The largest changes were seen on the SF 36 pain scale (effect size 1.2 at three months, 1.5 at 6-12 months), physical function (1.1, 1.3) and role limitation--physical (0.8, 1.2) scales. The London Handicap Scale also measured large changes (effect sizes 0.6, 0.9), but the Extended Activities of Daily Living scale was insensitive to change (effect sizes 0.1, 0.2). CONCLUSIONS: Some of the SF-36 dimensions were very sensitive to change. The London Handicap Scale was also reasonably responsive, and has the advantage of being a single, utility-based, score. The simpler Extended ADL score was poorly responsive. PMID- 11194620 TI - The mediation of disability by self efficacy in different samples of chronic pain patients. AB - PURPOSE: A path analytic model conceptualizing self efficacy as a mediator of disability was tested. This model could help explain the circumstances under which disability develops more in some chronic pain patients than in others. METHOD: Questionnaires from 479 chronic pain patients were collected prior to an initial consultative visit with a pain specialist at three pain clinics. These patients represented three separate samples. One sample from a tertiary care hospital (n = 226), one from a community-based clinic (n = 137) and a third sample from combined settings, but excluding patients with a history of depression prior to the onset of their pain (n = 116). Hypothesized and alternative models were tested to identify the model best fitting these data. RESULTS: Regression analysis supported self efficacy as a mediator of the relationship between pain intensity and disability (p < 0.001) in all three groups. This model was best supported in the group with no prior depression (accounting for 47% of the explained variance in disability). The 'no-prior depression' group was different than the other samples in that depression did not contribute to disability in this sample where prior depression was not controlled for. CONCLUSION: Self efficacy in an important variable contributing to the disability of chronic pain patients. Therefore, evaluating and bolstering the patient's belief in their own abilities may be an important component of therapy. PMID- 11194621 TI - An exploration of the Malawian perspective on children's everyday skills: implications for assessment. AB - PURPOSE: The aim of this study was to consider Malawian concepts of psychosocial development in children and to draw implications for the devising of an instrument to measure everyday skills in children. METHOD: Key informant interviews, focus groups and other interviews, video tapes and observations of children were undertaken in a rural village in Malawi, with a focus on 4-5-year olds. RESULTS: A well adapted child of this age is expected to show first of all understanding of social responsibilities, with regards respect, obedience, cooperation, ability to socialize with other children, ability to carry out 'children's chores', to know people by names but more importantly how they are related to the child. The child should also show memory skills sufficient to carry messages. Such a child is described as intelligent/clever, characteristics important for survival. CONCLUSION: There are significant implications for the justification for the development of an instrument to measure everyday skills in African communities. PMID- 11194622 TI - Critical illness polyneuropathy: a summary of the literature on rehabilitation outcome. AB - PURPOSE: To evaluate the available literature on outcome of critical illness polyneuropathy (CIP) and to identify rehabilitation problems. METHODS OF STUDY SELECTION: A literature search in electronic databases. Primary articles on outcome in CIP using the classification of ICIDH or Quality of Life were enrolled in this study. Because of the types of study design, the lack of information regarding validity and the variability, a quantitative analysis was not possible. Instead, the overall results were evaluated in a qualitative approach. RESULTS: In the literature minimal attention was given to the rehabilitation aspects and long-term outcome of patients with CIP. Outcome measures were mainly used on the level of impairments and in lesser extent on the level of disabilities. One year after the onset of CIP, muscle weakness and decreased sensory function were frequently observed. Reported functional disabilities were dependency in Activities of Daily Living (ADL) and walking disabilities. CONCLUSION: The specific course and long-term outcome of CIP remains unclear. Research on the course and long-term functional outcome in CIP is necessary in order to identify rehabilitation problems and to formulate treatment strategies specifically directed towards the outcome of CIP. PMID- 11194623 TI - [Intravesical chemotherapy with mitomycin C after TUR for superficial bladder carcinoma]. AB - Fifty-four patients mean aged 58.5 years (28 women and 26 men) undergo transurethral resection for superficial bladder carcinoma. Postoperatively 20 mg mitomycin is administered by instillation into the bladder for 8 weeks. Preoperative assessment includes: complete blood count, urea, creatinine, isotope nephrography, ultrasonography, excretory urography and CT scan of pelvis. Multifocal lesions are diagnosed in 22 patients (40.7%). In 36 cases (66.7%) it is a matter of solitary papillomas. The distribution of lesions is as follows: left bladder wall--12 patients (22.2%), right bladder wall--13 (24.07 per cent), trigone--18 (33.3%), and anterior bladder wall--11 (20.03 per cent). Postoperative check-ups: cytological assessment of urine and regular endoscopic study at 3-6 months. Recurrence rate amounts to 42.5% for the maximum follow-up period. PMID- 11194624 TI - [Serious infections associated with transurethral operations for lower urinary tract obstruction]. AB - Serious urinary infections associated with transurethral surgery are a problem of current interest. The underlying causes of their occurrence and the therapeutic approach used are discussed. The study covers 139 patients treated over a two year period. The types of diseases giving rise to lower urinary tract obstruction and the transurethral operations performed--optic urethrotomy, laser photocoagulation and transurethral resection--are analyzed. In all patients sterile urine assessment is done before, during and after treatment. Identification of the bacterial strains and antimicrobial sensitivity testing are conducted with mini API system--Bio-Merieux, France. The frequency of microbical causing agents and their antibacterial resistance are studied. The tactics in selecting the most adequate drug is discussed. Pseudomonas aeruginosa is identified as urinary infection cause in 49.5 per cent. Good results are obtained in 118 patients (84.9%); among those without urethral catheter prior to operation -97.3 per cent, and in the group with urethral catheter--70.3 per cent. Conclusions are drawn concerning the necessity of microbiological study of the urine in transurethral operations, and undertaking treatment in due course. Retaining of the indwelling urethral catheter prior to intervention should be reduced to a minimum. The clinical efficacy of oral beta-lactams is lower by comparison with fluoroquinolines owing to the multiple resistance of strains. The tenets of picking out an antibiotic for handling significant urinary infections are outlined. PMID- 11194625 TI - [The most common complications associated with nephrectomy]. AB - Access to the kidney and technical performance of nephrectomy should be related to the stage of the disease and degree of pathological process development (I. Viktorov 1983, S. Lambrev and T. Andreev 1961, T. Patrashkov 1982, F. S. Judy et al 1995). Advanced pathoanatomical changes in the kidney and pararenal space greatly interfere with the operation, especially in the event of adhesions to peritoneum and contiguous tissues (N. A. Lopatkina et al 1986, N. Minkov 1987, T. Patrashkov and H. Kumanov 1988). In the authors' reports presented are analyzed 388 patients nephrectomized in the University Hospital "Alexandrovska", covering the period 1990 through 1995. All updated methods are used in diagnosing. The commonest intraoperative complications recorded in a series of 188 nephrectomies (48.45%) include: 1. Pus collections in the kidney--88 cases (46.80%). 2. Opening of peritoneum--64 (34.04%). 3. Decompressive puncture of the kidney--15 (7.97%). 4. Neoplastic masses escaping from the renal parenchyma into the operative field- 7 (3.72%). 5. Opening of pleura--5 (2.66%). 6. Purposeful opening of the tumor itself for decompression--3 (1.95%). 7. Kidney removal gives rise to diffuse bleeding necessitating inserting a tampon for hemorrhage control--2 (1.06%). 8. Splenectomy--1 (0.53%). 9. Because of advanced neoplastic process only biopsy is taken--1 (0.53%). 10. Hemicolectomy--1 (0.53%). 11. Injury to v cava inferior--1 (0.53%). As shown by the experience gained, nephrectomy is a technically difficult operation, particularly in case of altered topoanatomical interrelations during secondary interventions on the kidney and ureter, or in case of concomitant pyelonephritis. Intraoperative complications are not life endangering provided treatment is undertaken in opportune time. PMID- 11194626 TI - [Mucinous breast carcinomas with neuroendocrine differentiation]. AB - Mucinous breast carcinomas, denominated also gelatinous, mucoid and colloid (collomas), represent a heterogeneous group of neoplasms. More than half of them exhibit signs of neuroendocrine differentiation. Eighteen mucus producing carcinomas of the breast are subjected to morphological study. On the ground of demonstrating argyrophilia by the methods of Grimelius and Churukian--Shenk, and presence of secreting granules during electron microscopic study, they are assigned under the heading apudomas, i.e. tumors of the diffuse endocrine system, or the so-called APUD-system. The important practical implications of demonstrating neuroendocrine cells with a special reference to the biological patterns of this particular type of tumors are discussed. PMID- 11194627 TI - [Mammary gland carcinoma in men]. AB - Over a 10-year period, a total of 403 patients with mammary gland carcinoma--398 women (98.8%) and five men (1.2%)--are operated in the Clinic of Thoracic Surgery & Oncology at the Military Medical Academy. The mean age in men, as compared to that in women, is nearly 12 years older. In one patient tumorectomy is done for "cleanliness" on account of the seriously impaired general condition. In the remainder the operative intervention is radical mastectomy after Patey or Pirogov, with meticulous axillary lymph dissection. In all men operated on, gynecomastia concurrent to the underlying disease is found. The histological patterns of mammary gland cancer in male patients is identical to the histological picture in women. PMID- 11194628 TI - [Carotid body tumors - diagnosis and treatment]. AB - Carotid body tumors are rare, with a tendency of slow but progressive growth, giving rise to external compression and/or involvement of the carotid arteries, craniofacial nerves and other neighbouring structures. They are adequately vascularized, with surgery being the treatment of choice. Localization and vascularity require comprehensive understanding of the anatomy, and most likely, vascular surgeons with carotid experience and neurosurgeons would make the best teams. In certain cases the participation of craniofacial surgeon is likewise needed. Over the period 1989 through 1999, in the Department of Vascular Surgery, six patients presenting carotid body tumor are treated. There is not a single case with bilateral involvement, and all have negative family history for carotid body tumor. Two of them are subjected to explorative surgery elsewhere. Two patients only are asymptomatic. In 3 patients CT of the neck, and in one--MRI are used as diagnostic modalities. Five patients undergo carotid artery ultrasonography, and three--angiography. Internal carotid clamping is necessitated in one case only, undergoing explorative surgery at another hospital and presenting a big tumor, stage III (Shamblin). Postoperatively, the patients complain of slight deviation of the tongue and slurred speech. The check-up carotid ultrasound shows hemodynamically relevant stenosis of the internal carotid artery, 1 cm distally to the carotid bifurcation, without flow into the external carotid being detected. On follow-up, all patients are alive and free of local recurrences or metastases. PMID- 11194629 TI - [Foreign bodies in the upper airways of children - problems relating to diagnosis and treatment]. AB - The authors share their experience and systematic observations with regard to the correlation between "chronic pneumonia" and foreign bodies in the respiratory tract, based on a survey of 480 bronchoscopic examinations for a period of 10 years. It was established that misdiagnosed foreign bodies in the lower respiratory tract account for 12.5% of all these cases. The percentage of undiagnosed bilateral foreign bodies is unusually high, as well as that of the left-sided foreign bodies, although to a smaller degree. The study also shows that very often in pediatric practice foreign bodies are wrongly diagnosed as bronchopneumonia and bronchial asthma. PMID- 11194630 TI - [Complications in Le Fort facial fractures combined with craniocerebral trauma]. AB - The present research is based on the most frequent traumas and fractures in the middle zone of the face (second and third type by Rene le Fort) and the proceeded from them complications for a period of four years in the clinic of Neurosurgery in NIUMN "Pirogov". From the 280 patients that were studied the complications were observed in 54 of them. We worked up the received results statistically and presented them in drawing. PMID- 11194631 TI - [History of nephrectomy]. AB - Following animal experiments (Combair 1803, Prevost and Dumas 1823) and accidental removal of the kidney in humans (Spillgellberg 1867, Peaslee 1868, Wolcott 1886), it has been established that elimination of a single kidney does not lead mandatorily to fatal outcome if the second functioning kidney is preserved. The chronology of nephrectomy development on a worldwide scale, and in Bulgaria as well, after the first routinely scheduled nephrectomy performed by Gustav Simon (2 Aug 1869), is presented. In 1897, almost 30 years later, Ivan Mikhaylovsky from the Plovdiv Hospital performed the first nephrectomy in this country. In the late 19th and early 20th century, nephrectomy becomes one of the most often used kidney operations (H Kumill, 1913--49.3 per cent), but gradually parallel to improving the diagnostic technique it is less frequently applied (W Lutzer et al, 1976--28 per cent) at the expense of organ-salvaging interventions. The last decade marks the introduction of laparoscopic nephrectomy (RV Clayman et al, 1991, AD Joce et al, 1992, JJ Rassweller et al, 1993, Sy Nakada et al, 1996, CC Abbou et al, 1998) which is a safe procedure even in patients with malignant renal pathology and adequately selected cases presenting various urological diseases. PMID- 11194632 TI - [Case of an adult female operated successfully for Boerhaave's syndrome]. PMID- 11194633 TI - [Case reports on constrictive strictures of the esophagus]. PMID- 11194634 TI - [A rare case of scrotal calculosis in a male presenting hydrocele]. PMID- 11194635 TI - [Pseudolymphoma of the stomach]. PMID- 11194636 TI - [Bile duct anomalies and variations of arterial blood supply to the liver and gall bladder]. PMID- 11194637 TI - [Bladder neck reconstruction after radical prostatectomy]. AB - Experience had with radical prostatectomy in patients presenting localized prostate carcinoma is shared. A modified technique for new bladder-neck formation contributing to continence preservation is used in five patients, yielding very good postoperative results. In four cases a full recovery of continence is achieved within 3 months of the operation without resorting to drug therapy. In one case medical treatment with parasympaticolytics and agonists of voluntary sphincter is applied. The final outcome is stress incontinence only and passage of urine in the event of micturition postponed with 3-3.5 hours. PMID- 11194638 TI - [Methods most frequently used in the diagnosis of renal diseases leading to nephrectomy]. AB - In the past few years, the progress of science and technology, and introduction of new diagnostic and treatment methods (echography, isotope study, computerized axial tomography, renovasography, magnetic resonance imaging and others) have contributed greatly to early detection and timely treatment of pathological processes involving the kidney (ZK El-Zein, 1995). After practical implementation of new clinical methods of examination it becomes possible to gain better insight into the undelying causes and character of renal diseases (T. Patrashkov, 1982). The study covers 388 patients subjected to nephrectomy for various diseases of the kidneys and urether, diagnosed and treated in the Department of Urology University Hospital "Alexandrovska", over the period 1990 through 1995. The commonest diagnostic methods used to make diagnosis prior to nephrectomy include: 1. Survey roentgenography of kidneys, urethers and urinary bladder (KUB)--364 (93.81%). 2. Venous urography--320 (82.47%). 3. Echography--302 (77.83%). (Antegrade pyelography--2 (0.51%). 4. Isotope nephrogram (ING)--212 (54.63%). 5. Scintography of kidneys--126 (32.47%). 6. Computerized axial tomography (CAT)--82 (21.13%)/(70.68%) among 116 renal tumor nephrectomies. 7. Renovasography--82 (21.13%). 8. Retrograde pyelography--48 (12.37%). 9. Gamma-camera--10 (2.57%). 10. Cystoscopy--6 (1.54%). 11. Ureterorenoscopy--2 (0.51%). Presumably, apart from the new "noninvasive" methods of study (computerized axial tomography--CAT and echography), the conventional venous urography has by no means lost its popularity. PMID- 11194639 TI - [Finite element analysis of an additional implant for intramedullary nailing]. AB - In the surgical treatment of fractured femurs, the fracture is bridged by a medullary nail fixed in the bone with interlocking screws. Failure of bone substance in the region of the interlocking screws is the most common complication in the treatment of osteoporotic bone. With the aim of preventing this complication, an additional implant was developed. A finite element analysis of an ideal bone/implant system was carried out to investigate the role of the additional implant. Three defined finite element models were generated, and the associated stress situations compared. The first model is a standard fixation without the additional implant. In the second model, the additional implant is integrated within the bone/implant system. The third model uses a modified form of the additional implant. The results show that both additional implants reduce the stresses occurring, both in the bone substance and at the screws. The modified form of the additional implant proved to be the most favorable version. In the case of the original additional implant, the negative effect of the sharp edges of the thread was demonstrable. PMID- 11194640 TI - [Assessment of bone healing during callus distraction by an automatic torsional stiffness metering system]. AB - The present article describes a newly developed device for the quantitative assessment of torsional in vivo stiffness of regenerating bone under callus distraction. Both the design and function of this device, and its use during bony consolidation are discussed. The device exhibited an accuracy of +/- 18% for stiffness under 0.1 Nm/degree, and +/- 5% stiffness above 0.1 Nm/degree. The average accuracy was +/- 14%. The data scatter for the stiffness measurement ranged between +/- 1.43% and +/- 7.68% (average: +/- 3.99%). The precision of a test machine was between +/- 0.01% and +/- 11.3% (average: +/- 3.65%). The method has the following advantages over existing methods for investigating healing: 1. no need to dismantle the external fixation for measurement; 2. preservation of the bone axis with minimal risk of misalignment during the bone healing process; 3. minimal technical requirements, with easy, noninvasive measurement; 4. no exposure to X-radiation. PMID- 11194641 TI - [Standardized testing of bone implant surfaces with an osteoblast cell culture cyste. III. PVD hard coatings and Ti6Al4V]. AB - The effect of titanium-based PVD coatings and a titanium alloy on the proliferation and differentiation of osteoblasts was investigated using a standardised cell culture system. Human fetal osteoblasts (hFOB 1.19) were cultured on titanium-niobium-nitride ([Ti,Nb]N), titanium-niobium-oxy-nitride coatings ([Ti,Nb]ON) and titanium-aluminium-vanadium alloy (Ti6Al4V) for 17 days. Cell culture polystyrene (PS) was used as reference. For the assessment of proliferation, the numbers and viability of the cells were determined, while alkaline phosphatase activity, collagen I and osteocalcin synthesis served as differentiation parameters. On the basis of the cell culture experiments, a cytotoxic effect of the materials can be excluded. In comparison with the other test surfaces, [Ti,Nb]N showed greater cell proliferation. The [Ti,Nb]N coating was associated with the highest level of osteocalcin production, while all other differentiation parameters were identical on all three surfaces. The test system described reveals the influence of PVD coatings on the osteoblast differentiation cycle. The higher oxygen content of the [Ti,Nb]ON surface does not appear to have any positive impact on cell proliferation. The excellent biocompatibility of the PVD coatings is confirmed by in vivo findings. The possible use of these materials in the fields of osteosynthesis and articular surfaces is still under discussion. PMID- 11194642 TI - [Simulator for migration processes and wear in the artificial hip acetabulum for radiologic measurement]. AB - For assessing migration of cups, standard X-rays or stereo radiological images (SRI) are available. In addition, software is also available for measurements. The accuracies of the various systems are established statistically, in part combined with phantoms, and compared. To date, no known phantom is available for the simulation of acetabular cup migration with account being taken of the position of the pelvis in the X-ray beam. Such an appliance covering 8 different parameters has now been developed, the cup can be moved horizontally, vertically and in the loading direction. Angular accuracy is +/- 0.5 degree, and wear of a magnitude of 0.25 mm can be simulated. Two degree elevation of the pelvis, left or right, can be simulated. The position of the pelvis around the horizontal axis permits continuous variation. This appliance can simulate migratory movements of the acetabular cup within a pelvis, and wear within the cup. In addition, the spatial position of the pelvis can be varied. The X-ray images can be used to investigate the accuracy of evaluation strategies. PMID- 11194643 TI - [Survival rate of the cemented Charnley total hip endoprosthesis and modifying parameters]. AB - AIM OF THE STUDY: To analyse survival of cemented Charnley prostheses, and influencing factors. MATERIAL AND METHODS: 539 patients (mean age: 62 years) undergoing 426 primary, and 200 revision Charnley hip arthroplasties, were examined. The indications for primary operation was idiopathic coxarthrosis in 239 cases (56.1%), and rheumatic coxarthrosis in 56 cases (13.1%). Reasons for revision surgery included aseptic loosening in 123 cases (61.5%), septic loosening in 36 cases (18%), and prosthetic fracture in 13 cases (6.5%). RESULTS: After a mean follow-up of 4.4 years, patients were scored using the Merle d'Aubigne evaluation. The average postoperative score for primary operations was 14.8 points, and for revision surgery 13.1 points. The respective pre-operative scores were 8.2 and 8.1. Radiographic investigation revealed peri-articular calcifications in 28.4% of the primary operations, and in 28.5% of the revisions. Radiolucent lines or protrusions were found in 29.8% of the primary, and in 42.0% of the revisions. At follow-up, 45 implants in 41 patients had been replaced. Kaplan-Meier survival rates for the primary group were 99.6% after one year, 92.8% after five years, 78.3% after 10 years, and 45.9% after 15 years. The respective figures for the revision group were 98.2%, 85.3%, 59.7% and 31.3%. The largest difference was seen in the eleventh year. Patient age had no significant influence for the first 12 years. In the primary group, body mass index showed a significant influence only after 15 years. Analysis of the indications for surgery revealed a slightly higher survival rate in the arthrosis group (84%) vis a-vis the dysplasia group (83.3%), and a significantly higher rate vis-a-vis patients with rheumatoid arthritis (42%). CLINICAL RELEVANCE: Such factors as age, diagnosis and weight had an influence only over the long term. Significant differences between primary and revision operations were not found. PMID- 11194644 TI - [Ceramic acetabulum for hip endoprostheses. 8: Revisions]. AB - For total hip replacement, ceramic femoral heads and acetabular liners are being used with success. However, reports of revision surgery necessitated by fractures or marked wear of ceramic components are still being published. The revision rate due to fracture is less than 0.01%, and much lower than for other complications. Nevertheless, improvement of safety remains a topic of discussion. This article reviews the results of investigations of explanted ceramic heads and liners, and discusses the problems caused by ceramic wear and chipping. Recommendations for revision surgery in such cases are given. PMID- 11194645 TI - [ESKA-Ceram--a new material in hip endoprosthetics]. AB - ESKA-Ceram is a new material for use in hip endoprostheses, and comprises two thirds polyurethane and one-third Al2O3 ceramic powder. Its wear rates are of a similar low order of magnitude as those reported for metal-metal and ceramic ceramic combinations. A great advantage of the material is that it permits the production of asymmetrical inserts for acetabular cups. PMID- 11194646 TI - [Problems relating to vascular reconstruction in renal transplantation from a living donor]. AB - We discuss vascular surgical problems in 59 kidney transplantations using alive donors. From April 96 till May 99 we harvested 59 kidneys from relatives (44 women and 15 men), mean age 54.33 years. Those kidneys were transplanted to 37 men (mean age 55.71 years), and 22 women (mean age 36.85 years). Preoperative dialysis was performed for a period of 5.015 years (mean). Thirty eight of the kidneys are right, and 21 of them are left. Six kidneys have two renal veins (10.16%), and 5 of them have two renal arteries (8.47%). We prefer end-to-end anastomosis between the donor renal artery and the recipient hypogastric artery. It ensures best regional hemodynamics, long-term patency and best positioning of the kidney avoiding vascular compression. The venous anastomosis is performed end to-side to the iliac vein of the recipient. In 7 cases of short renal artery of the donor kidney greater saphenous vein is used as arterial conduit to ensure tension-free anastomoses. Only 1 patient (1.74%) of 59 cases (71 venous anastomoses) suffered thrombosis of the iliac vein, which caused kidney rupture. We had 5 cases of postoperative bleeding (8.47%), three of them were from the kidney hilus, and two from exposure sites. After reexploration all of them have normal function. Vascular anomalies and/or vascular disease do not preclude the procedure. Atraumatic harvesting of the kidney is critical. PMID- 11194647 TI - [Our experience in the diagnosis and treatment of carotid-jugular fistulae]. AB - We present our experience in treatment of patients with carotid-jugular fistulas for a three years period. Three of those patients had congenital fistulas and one had acquired (posttraumatic) fistula. Signs and symptoms include: pulsatile neck mass, systolic murmur, thrill, dilated superficial veins. Diagnosis was confirmed with Duplex ultrasonography and angiography. Patients were treated by open surgery (ligation and resection) and endovascular procedures (conventional and laser embolization). In cases of single A-V communication ligation and resection gives excellent results. In cases of multiple communications recurrence in the same or neighbouring vascular area is more likely and second stage surgery or/and endovascular procedures (embolization) may be needed. PMID- 11194648 TI - [Post-cystectomy derivations - a rule or control of technical skills?]. AB - Limitations in gaining better understanding of bladder tumor responsiveness do exist, and accordingly the therapeutic interventions undertaken in diverse forms of the disease are conspicuous for discrepancies (M. J. Droller, 1990). E. Bricker in 1950 is the first to practically implement ileal conduit for urine derivation, and thus initiates the new and newest continent derivations. Over the period 1992-1998, in the Chair of Urology are performed 76 cystectomies with different urine derivations, using seven methods for the purpose: [table: see text] Also discussed are the conditions a derivation should mandatorily meet. Emphasis is laid on the fact that the choice of derivation is still largely dependent on the skill and experience of urologists. PMID- 11194649 TI - [Endoscopic treatment of upper urinary tract obstruction]. PMID- 11194650 TI - [Therapeutic approach to upper urinary tract obstructions (UUTO) of gynecologic nature]. AB - The existence of numerous treatment methods for upper urinary tract obstructions (UUTO) following gynecological interventions, taken alone demonstrates that it is a matter of a complex surgical problem, hardly lending itself to solution. There is no ideal operation, manipulation or procedure. It is precisely the role of the urologist to choose and implement in practice the most adequate therapeutic approach to each individual case. Urology is an interdisciplinary and extensive surgical speciality, disposing of both classical, well-tried operative procedures, and vast possibilities for performing minimum invasive interventions and manipulations. All treatment approaches to UUTO after gynecological operations used in the Chair of Urology are described and comprehensively discussed. PMID- 11194651 TI - [Long-term results of 516 transurethral resections of the prostate gland]. PMID- 11194652 TI - [Duodenal decompression in the surgical management of complicated ulcers]. AB - Operative duodenal decompression for correction of and prophylaxis against duodenostasis is discussed. The methods used for treating complicated pyloric or duodenal ulcers include: perforation suture according to Opel-Polykarpov, resection of the stomach after Billroth-Haberer-Finney, resection of the stomach after Billroth-Vitebsky. All procedures listed above are performed in conjunction with operative interventions aimed at duodenostasis decompression. PMID- 11194653 TI - [Hair transplantation with Calvitron - experience with 25 patients (preliminary report)]. AB - Between 20 and 30% of the male and 5% of the female population is affected by baldness. This 'androgenic' alopecia is linked to a genetic and hormonal characteristic. The surgical options for the treatment of the alopecia are numerous, however none of it do not produced single solution that is applicable to all problems. In approximately 90% of the cases treated, the hair graft transplants comes to the forefront of the therapeutic methods. The method is applied in 25 patients and the Calvitron was used for the purpose. The patients were followed for 6 months after the implantation. From 300 to 620 grafts or 600 to 1200 hair follicules were implanted in one section. PMID- 11194654 TI - [Complications in plastic surgery breast reconstruction with TRAM flap. Preventive methods and treatment modalities]. AB - The breast reconstruction with the TRAM-flap is sophisticated and demanding procedure, requiring careful planning and technical proficiency. Despite these efforts, the outcome of the breast reconstruction can be compromised by factors such as vascular insufficiency, scar contraction, errors in planning of the flap, or in the technique of building the new breast. Preventing the problems and complications in breast reconstruction require careful preoperative study, proper patient selection, accurate analysis of the results and immaculate technical performance. PMID- 11194655 TI - [Combined and extended radical operations in colorectal carcinoma patients]. AB - This is a report on radical operative interventions performed in 273/385 patients presenting complicated colorectal carcinoma, covering the period 1993 through 1998. Fifty-four patients are subjected to combined and extended operations, distributed as follows: 31 combined and 23 extended. In fifteen patients with abdomino-perineal extirpation the combined interventions include: hysterectomy (6), ovariectomy (8), resection of vagina (7), prostate gland resection (3) and bladder resection (2). In case of resection of rectum after Hartmann, combined intervention is done in five patients--small intestine resection, ovariectomy, appendectomy and cyst extirpation from pelvis minor, respectively. Postoperative lethality amounts to 12.9 per cent, or 7/54 patients with complicated colorectal carcinoma undergoing combined and extended surgical interventions. PMID- 11194656 TI - [Orthotopic liver transplantation - recipient selection criteria]. AB - In a great number of patients with progressive liver diseases whose terminal phases are cirrhosis and hepatic insufficiency, liver transplantation is the only feasible therapeutic alternative. However, the undertaking of liver transplantation is largely dependent on the availability of donor organs. Hence, the process of selecting the most adequate recipient is of critical importance from both medicolegal view-point, and in terms of the likelihood of a successful outcome of transplantation. The study is designed to asses the problems faced with a special reference to indications, contraindications and timing of liver transplantation. PMID- 11194657 TI - [Monitoring phagocytic activity in acute pancreatitis patients (mild and severe forms)]. PMID- 11194658 TI - [Bilateral thoracotomy with transverse sternotomy in bilateral pulmonary echinococcosis]. PMID- 11194659 TI - [Volvulus of the stomach]. PMID- 11194660 TI - [Wegner granulomatosis with initial manifestation of bilateral granulomatous purulent necrotic mastitis]. PMID- 11194661 TI - [Case report of combined variation of the branches of the subclavian and superior thyroid arteries]. PMID- 11194662 TI - [Creation of an orthotopic urinary bladder from ileum - "St Anna's" procedure]. PMID- 11194663 TI - [Therapeutic approach to postoperative dysphonia following thyroid gland surgery]. AB - The recurrent nerve palsy, which is frequently expressed clinically by postsurgical dysphonia is quite often a complication in the thyroid surgery. The choice of therapeutic behaviour is based on the assessment of the clinical condition of the patient, in other words, whether the dysphonia is accompanied by dyspnoea or not. 32 patients with postsurgical dysphonias are included in the survey. All patients were operated for thyroid disease in the Clinic of Endocrine Surgery between August 1996 until May 1998 and surveyed for a follow-up period of 3 to 21 months. The analysis of the results shows that the conservative treatment is appropriate for patients with functionally well compensated dysphonias, whereas the existence of high-level dyspnoea, whose morphologic substratum is most frequently a bilateral recurrent nerve palsy with median position of the vocal folds, necessitates surgical treatment. PMID- 11194664 TI - [Notes on some operative procedures in chest surgery]. AB - Experience with some useful procedures in chest surgery, gained over a 35-year long clinical practice, is shared. The items discussed include: Lever assisted retraction of the intercostal space in thoracotomy. Preventive paravertebral excision of a rib in thoracotomy. Costal resection during thoracotomy. Hemostasis through aspiration electric cautery in thoracotomy and mediastinoscopy. Continuous running suture of bronchial stump and pulmonary parenchyma. Plastic bronchial stump hermetization. Pleural cavity drainage following inferior bilobectomy. Douche lavage for topical management of post-pulmonectomy empyema. The methods briefly outlined are addressed mainly to young chest surgeons in post graduate training. PMID- 11194665 TI - [Primary colorectal carcinoma as an underlying cause of obturation of the ileum]. AB - This is a report on 169 patients presenting colorectal carcinoma with complication assuming the form of occlusive ileus, observed over the period 1993 through 1998. Obturation is the commonest complication of colonic carcinoma (48.9%) with the left colon being more often involved (58.3%), recorded in a total of 108 patients. During the same period of time, occlusive ileus against the background of carcinoma of the rectum is diagnosed in 61 cases, representing 37 per cent of complicated forms of this malignant neoplasm. The scope of operative management and the procedure used are largely determined by the location of primary malignancy. The timing of undertaking one or another operative intervention depends on the efficacy of preoperative preparation, degree of occlusive ileus progress, patient's age, concomitant diseases and the like. Failing to comply with or overlooking some of the aforementioned factors invariably exerts an unfavourable effect on the final outcome of treatment. In each patient presenting colorectal-carcinoma-induced occlusive ileus it is mandatory to precisely specify the scope of surgery, consistent with the patient's general condition, and eliminate the underlying cause jeopardizing his life. PMID- 11194666 TI - [Cosmetic rhinoplasty: open versus closed access. Results with 70 patients]. AB - Because of its central location, the nose is an important element in facial aesthetics. The size and the shape is conditioned by the volume and the strength of the osteocartilaginous framework and the thickness of the soft-tissue cover. Rhinoplasty is a complex procedure requiring understanding of the anatomy and how each element contributes to the shape of the nose. In an attempt to obtain a pleasing aesthetic result and to have a satisfied patient 70 patients were operated. The results of open and closed approaches in rhinoplasty and the indications for the open approach are discussed. PMID- 11194667 TI - [Characteristic features of anesthesia in post-mastectomy mammary-gland reconstruction]. PMID- 11194668 TI - [Current diagnosis of upper urinary tract obstructions (UUTO) of gynecologic origin]. AB - Upper urinary tract obstructions represent a problem faced by urological specialists for many decades. Regardless of the updated methods of diagnosing and management, as well as the attempts at early detection of neoplastic diseases and their complications, there is a permanent tendency of the morbidity rate of carcinoma of the uterine neck and body to increase. What is more, age stratified morbidity most frequently demonstrates involvement of women in the 40-49 years age group. In the daily routine urological practice cases presenting UUTO are by no means rare, and not infrequently urologists confront a queer challenge necessitating to make exact diagnosis in opportune time. It is the purpose of the study to present a summed up assessment of the diagnostic methods most frequently used. PMID- 11194669 TI - [Obstruction of the upper urinary tract following gynecological interventions for neoplastic diseases of female genitalia]. PMID- 11194670 TI - [Radical prostatectomy with broadened scope of indications - analysis of early experience]. PMID- 11194671 TI - [Rupture of abdominal aortic aneurysm into inferior vena cava]. PMID- 11194672 TI - [Combined surgical treatment of patients with huge aortic abdominal aneurysms associated with coronary artery lesions]. AB - The objective of this study was to define the perioperative risk of simultaneous operations in patients with abdominal aortic aneurysm (AAA) associated with coronary artery disease (CAD). The hospital data of 30 patients with coexistent severe symptomatic AAA and significant CAD, who underwent one stage surgery of the abdominal aorta and the coronary arteries was retrospectively analysed. Most of the pts.--28 were male and only 2 female. The average age consisted 57.7 years. Infrarenal AAA (diameter over 5 cm) was presented in 25 patients and suprarenal extension was in presented in 5 pts, while all patients with coexisting CAD had three vessels disease and significant impairment of left ventricular function (23 pts with ejection fraction (EF) < 50% and 10 pts < 30% EF). The resections of AAA in pts. undergoing simultaneous coronary artery procedure were performed on cardiopulmonary bypass (CPB) and moderate hypothermia. There were 2 early postoperative deaths (6.66%) and 5 major nonfatal postoperative complications (16.6%). Our experience with simultaneous surgery of coexistent huge AAA and CAD demonstrated that: a) Combined procedure can be performed safely in patients with significant AAA and CAD. b) The overall early operative mortality and morbidity after combined surgery compare favourably with the results after CABG of patients with impaired left ventricular function. c) Simultaneous operation seems to be more favourable in patients with coexistent AAA and CAD regarding the high risk of aneurysmal rupture, saving them also the potential morbidity and eventually fatal complications associated with the second procedure. d) Even the management of suprarenal and huge infrarenal AAA can be carried out easier and with less risk of complications under the protection of CPB. PMID- 11194673 TI - [Case of successful lung carcinoma surgery in a 78-year-old male patient]. PMID- 11194674 TI - [Clinical and anatomical aspects of muscles within the deep anterior perineum of women]. PMID- 11194675 TI - [Obturation of infrainguinal arteries - clinical picture and surgical management]. PMID- 11194676 TI - Six sigma. PMID- 11194677 TI - A remote possibility. PMID- 11194678 TI - A veteran physician's view of the future. PMID- 11194679 TI - A community of physicians. PMID- 11194680 TI - The emergence of the acute care nurse practitioner. PMID- 11194681 TI - Hospitalists redefine the future of inpatient medicine. PMID- 11194683 TI - Small is beautiful, say independent physicians. PMID- 11194682 TI - Elections 2000: the future of health care. PMID- 11194684 TI - Health policy report. Health and health services utilization--what determines what? PMID- 11194686 TI - Chronic appendicitis: it does exist. PMID- 11194685 TI - Loss prevention case of the month. Costly error in judgment. PMID- 11194687 TI - Comparison between vaginal misoprostol and cervical dinoprostone for cervical ripening and labor induction. AB - OBJECTIVE: To compare the efficacy of intravaginal misoprostol (Cytotec) to intracervical dinoprostone (Prepidil) for pre-induction cervical ripening. METHODS: Sixty-one patients admitted for induction of labor, whose cervices were unfavorable (Bishop score: 4), were randomly assigned to either intravaginal placement of a 50 micrograms misoprostol tablet or intracervical administration of dinoprostone gel. RESULTS: Eighteen women (56%) in the misoprostol group and five (17%) in the dinoprostone group achieved cervical ripening within 12 hours (P = 0.007). Fewer doses of misoprostol were required to achieve cervical ripening, and the interval from induction of labor to delivery was shorter in the misoprostol group. Sixteen patients (50%) in the misoprostol group required oxytocin, whereas 26 (90%) in the dinoprostone group required oxytocin augmentation (P = 0.008). There was no significant difference in mode of delivery or neonatal outcome between the two groups. CONCLUSION: Vaginal misoprostol appears to be a more effective cervical ripening agent than cervical dinoprostone. PMID- 11194688 TI - Department of Health Report. Care coordination and Children's Special Services. PMID- 11194690 TI - Opportunities to improve Mississippi's quality of medical care. PMID- 11194689 TI - A therapeutic nightmare. (loss prevention case). PMID- 11194691 TI - Mineral starvation. 1913. PMID- 11194692 TI - Sources of medical information for patients at civilian and Navy primary care clinics in Pascagoula, Mississippi. PMID- 11194693 TI - The 1878 yellow fever epidemic in Memphis. PMID- 11194694 TI - Clustering of lifestyle behaviors: the relationship between cigarette smoking, alcohol consumption, and dietary intake. AB - PURPOSE: To examine relationships between cigarette smoking, alcohol use, and dietary intake. DESIGN: Respondents to the U.S. Department of Agriculture's Continuing Survey of Food Intakes by Individuals, a nationwide probability sample conducted from January 1994 through January 1997 (n = 23,602; response rate = 80%), were selected. Adults ages 19 years and older were grouped according to their smoking and drinking habits. Selected demographic variables, food group servings, food energy, and densities of selected nutrients were compared. SETTING: In-home interviews were conducted in the 50 states and the District of Columbia. SUBJECTS: The selected sample (n = 6745) included 3229 nonsmokers, 1701 former smokers, and 1808 current smokers, and 2284 abstainers, 2713 occasional drinkers, 1000 moderate drinkers, and 748 liberal drinkers. MEASURES: Responses to standard questionnaires were examined by Student's t-test, chi 2, one-way analysis of variance, and univariate and multivariate analyses of covariance. RESULTS: Men were more likely than women to be current smokers and liberal drinkers (64% vs. 40% and 62% vs. 38%). For both, the use of cigarettes and alcohol was closely related. An additive relationship was observed between smoking/drinking classification and lower food group servings and nutrient intakes. Although cigarette and alcohol use may have been underreported, these findings support previous ones showing poor food choices along with lower nutrient intakes as smoking and drinking increase. CONCLUSIONS: Smoking and drinking habits may alter individuals' food selections and nutrient intakes. Future interventions for health promotion may achieve greater success by targeting multiple risk factors simultaneously or sequentially. PMID- 11194695 TI - Implementing a dietary intervention in primary care practice: a process evaluation. AB - OBJECTIVES: Physicians acknowledge the need to advise their patients about dietary habits, but they may not have the training or tools to do this efficiently. In the context of a randomized trial, we investigated the feasibility of enlisting physicians to implement a dietary intervention in the primary care setting. METHODS: Physicians from 14 primary care practices were assigned via randomization to introduce a self-help booklet to promote dietary change at routine appointments. Delivery of the booklet was recorded by these intervention physicians at the clinic appointment; intervention participants were asked 3 months later in a telephone interview about whether they received and used the booklet. RESULTS: According to physician documentation, 95% of intervention participants who kept an appointment (n = 935) received the booklet; among participants completing a 3-month interview (n = 890), 96% reported the same. However, only about 50% of participants reported receiving the booklet from their physician; the remainder received the booklet from other clinic staff. Overall, 93% reported reading at least part of the booklet. Use of the booklet varied little whether it was delivered by a physician or staff person, but it was more likely to be read as time spent discussing the booklet increased. CONCLUSIONS: Physician cooperation and evidence of intervention effectiveness support the use of primary care for the delivery of interventions to change diet; training the entire health team and repeating dietary advice at subsequent visits may improve the success of such interventions. PMID- 11194696 TI - Increasing the reach of health sponsorship: using a "sponsorship kit" to promote health. AB - In Australia, a tobacco tax provides funding for Healthway, the Western Australian Health Promotion Foundation. Healthway provides sponsorships for the arts and racing and sporting events to replace funds previously provided by tobacco companies. These sponsorships provide visibility for Healthway and positive health messages. Normally, Healthway staff attends these events to help promote health messages. To reduce Healthway staff time spent helping event organizers promote health messages, Healthway developed a sponsor kit of promotional materials which communicate health messages without requiring Healthway staff to attend events. Recognition, awareness, comprehension, and acceptance of health messages was comparable at events that featured Healthway staff versus the sponsor kits, but the average cost of the sponsorship kits was only 40% of the cost when Healthway staff was featured. PMID- 11194697 TI - Patterns of health promotion programs for older adults in local health departments. AB - Questionnaires were sent to all 2561 members of the National Association of County Health Officers in 1996; only 492 (19.2%) responded. Almost all departments have health promotion or disease prevention programs available to older adults, but only three-fifths specifically target older adults with these programs. Most of those programs are clinical preventive services, including immunizations. PMID- 11194698 TI - Physical activity patterns and body mass index scores among military service members. AB - Questionnaires on exercise practices, reasons for exercising, factors that would increase exercise, and demographics were mailed to a stratified random sample of 19,510 active duty personnel in all of the United States military services who were stationed at 38 large military installations and a number of remote locations. Responses were returned by 8,572 (55%). Approximately 63% exercised three times a week for 15-20 minutes, and 15% did not exercise at all. Mean BMI was 25.2. The top five reasons for exercising were to improve physical conditioning, have fun, manage weight, improve appearance and manage stress. PMID- 11194699 TI - The relationship between home smoking bans and exposure to state tobacco control efforts and smoking behaviors. AB - PURPOSE: To examine the relationship between home smoking bans and adult smokers' exposure to the statewide California Tobacco Control Program (TCP) and their cigarette smoking behavior. DESIGN: Cross-sectional survey that was part of the statewide Independent Evaluation of the California Tobacco Control, Prevention and Education Program. SETTING: Random telephone interviews within 18 California counties. SUBJECTS: A representative sample of 1315 adult smokers, aged 25 years and older. MEASURES: The telephone survey included questions about smoking behavior, quitting smoking, exposure to tobacco control program components, home smoking rules, and attitudes related to tobacco use and environmental tobacco smoke (ETS). RESULTS: Smokers with a home smoking ban were twice as likely (OR = 2.29; 95% CI 1.22, 4.29) to have heard of TCP community programs and three times more likely (OR = 3.18; 95% CI 1.34, 7.57) to have seen and talked about the ETS media spot than smokers with no home smoking policy. Multivariate regression models indicated that having a home smoking ban was related to smoking fewer cigarettes per day and greater interest in quitting smoking compared with smokers with no smoking rules in the home (p < .05). CONCLUSIONS: These findings suggest that smokers reporting exposure to the California TCP were more likely to have restrictive home smoking policies and that more restrictive home smoking policies were associated with reduced smoking behavior. PMID- 11194700 TI - The social context of experimenting with cigarettes: American Indian "start stories". AB - Smoking rates among American Indians are higher than any other racial or ethnic group. Focus groups were conducted with 140 American Indian middle school students who were not living on reservations to explore the social context of smoking initiation. Most teens smoked their first cigarettes with friends, siblings or cousins, usually out of curiosity, or in response to peer encouragement. There was no indication of any link between smoking initiation and use of tobacco in traditional ceremonies. Overall, the social context for these teens was very similar to the social context of other teens in the United States. PMID- 11194701 TI - Stages of change and smoking cessation: a computer-administered intervention program for young adults. AB - Sixty-five college-student smokers were randomly assigned to a four-week computer administered, stage-based smoking control program or a four-week computer administered general health education control condition. At post-test, the percentage of students advancing to a higher stage of readiness to change was slightly higher among those in the stage-based program compared to the control condition. At seven month follow-up, both groups reported abstinence rates of approximately 30%. Continuous abstinence for 6 months was 19% for the stage-based group and 14% for the control group at the final follow-up. PMID- 11194702 TI - Impact of a telephone-based intervention on the reduction of health risks. AB - PURPOSE: Evaluate the long-term impact of telephone-based interventions that target high risk, ready-to-change individuals. DESIGN: Quasi-experimental design with pre/post comparisons of lifestyle-related health risks between participants and nonparticipants. SETTING: Six organizations from the private and public sectors. SUBJECTS: Subjects were 607 intervention participants who were compared with a control group of 1134 eligible nonparticipants. MEASURES: Health risk assessment at baseline and at an average of 2 years later measured risk in 13 lifestyle areas. INTERVENTION: Programs were offered in seven areas: back care, cholesterol control, eating habits, exercise and activities, stress management, tobacco use, and weight control. Each program was conducted by a trained health educator who provided information and counseling to facilitate change in the area selected by the participant. All counseling was done by telephone and included three to five contacts over a 1-year period. RESULTS: Binary logistic regression models controlling for gender and age revealed both specific and general effects. Participants were 1.8 to 3.5 times as likely as nonparticipants to reduce the targeted risk in six of seven risk areas. In addition, participants were 1.7 to 3.5 times as likely as nonparticipants to reduce their risks in nine of 13 areas not targeted by the intervention (i.e., general effect). Overall, participants significantly reduced their number of risks, whereas nonparticipants significantly increased their risk (difference of .85 risks). CONCLUSIONS: Results show that at-risk participants make long-term improvements in health risks directly related to the intervention in which they participate. Results also suggest that this intervention may help individuals develop behavior-change skills they can apply to other lifestyle issues. PMID- 11194703 TI - Delayed closure of epiphyseal cartilages induced by the aromatase inhibitor anastrozole. Would it help short children grow up? AB - Estrogens locally generated from androgen precursors due to the action of aromatase play a main role in epiphyseal cartilage fusion. Treatment with an aromatase inhibitor (anastrozole, 1 mg/day for 3 yr) in a boy previously operated on for a hamartoma causing precocious puberty and presenting with advanced bone maturation and nearly fused epiphyseal cartilages, slowed cartilage fusion consenting a higher final stature than expected (164.4 cm vs 158.4 cm). It is suggested that treatment with aromatase inhibitors, alone or in combination with rh-GH, may also be useful in children with constitutional short stature in order to delay epiphyseal closure and improve the final height. PMID- 11194704 TI - Neonatal and adult human heart tissues from normal subjects and patients with ischemic, dilated or hypertrophic cardiomyopathy express insulin-like growth factor binding protein-3 (IGFBP-3). AB - In the human fetus IGFBP-3 mRNA expression is most abundant in the skin, muscle and heart but circulating IGFBP-3 levels show age-related variations. In human heart tissues from controls and patients with either ischemic, dilated or hypertrophic cardiomyopathy (no.: 20, age-range from fetuses to elderly subjects) we determined the expression of cardiac IGFBP-3 mRNA by reverse transcriptase polymerase chain reaction (RT-PCR) and the protein by Western blotting. The same parameters were also determined in human livers. We detected IGFBP-3 mRNA in neonatal and adult as well as in fetal human heart tissues in both ventricles. Western blotting revealed the presence of IGFBP-3 in all the examined cardiac tissues. IGFBP-3 appeared to be more abundant in the heart than in the liver and in the failing hearts from patients with ischemic heart disease than in those with hypertrophic cardiomyopathy. Thus both normal and pathological human heart tissues express IGFBP-3 across lifespan and IGFBP-3 could play IGF-dependent and/or -independent actions at the myocardial level. PMID- 11194705 TI - Bone turnover in hyperthyroidism before and after thyrostatic management. AB - Hyperthyroidism is associated with enhanced osteoblastic and osteoclastic activity, and patients frequently have low bone mineral density and high bone turnover. The aim of this study was to examine the bone formation and resorption markers trend in 12 female patients, before and after normalization of thyroid activity. The following measurements were made at baseline and 1 and 6 months after hormone normalization induced by methimazole treatment: total alkaline phosphatase (ALP), bone alkaline phosphatase (BALP), collagen type C-terminal propeptide (PICP), osteocalcin (BGP), telopeptide (ICTP), urinary hydroxyproline/urinary creatinine (uOHP/uCreat), urinary calcium/urinary creatinine (uCa/uCreat) and deoxypyridinoline crosslinks (D-Pyr). Compared with controls, all of these parameters were significantly increased (ALP p = 0.014; BALP p = 0.0001; PICP p = 0.013; BGP p = 0.009; ICTP p = 0.0001; uOHP/uCreat p = 0.002; uCa/uCreat p = 0.044; crosslinks p = 0.0001). After treatment the values of ALP, BALP and PICP in hyperthyroid patients showed an initial slight increase and then a significant downwards trend (ALP p = 0.008, BAP p = 0.001, PICP p = 0.026). Furthermore, resorption markers showed a significant decrease (uOHP/ uCreat p < 0.005 and D-Pyr p < 0.008). As regards lumbar BMD patients, measurements were significantly reduced in comparison with the control group (p = 0.005). Six months after serum thyroid hormones level normalization, we observed a significant increase (p=0.014 vs baseline). Both neoformation and resorption markers are useful to assess pathological bone turnover and bone involvement in hyperthyroidism. They could also be employed to monitor the effect of antithyroid treatment on bone and to indicate if bone antiresorption therapy should be considered. PMID- 11194706 TI - Oxidative markers in diabetic ketoacidosis. AB - Oxidative stress has been implicated in the pathogenesis of the chronic complications of diabetes mellitus but little is known in diabetic ketoacidosis (DKA). The aim of this work was to determine whether lipid peroxidation, as assessed by measuring malondialdehyde (MDA, a prooxidant) and antioxidant status (TAS, an index of antioxidant defenses), is modified in DKA, and also whether any observed abnormalities were related to metabolic disturbances. METHODS: four groups of patients were studied, comprising 19 patients with DKA, massive ketonuria and plasma standard bicarbonate levels below 16 mmol/l (group 1); 20 patients with poorly controlled diabetes, glycated hemoglobin (HbA1c) above 8% and plasma bicarbonate levels above 16 mmol/l (group 2); 11 patients with well controlled diabetes and HbA1c below 8% (group 3); and 10 non-diabetic, non-obese control subjects (group 4). Metabolic parameters, MDA levels and TAS were assessed in the plasma of the four groups of subjects. RESULTS: mean plasma MDA and TAS values were significantly different among the four groups (respectively p < 0.001 and p < 0.01). Mean plasma MDA value was significantly higher in group 1 than in group 3 (p < 0.02) and group 4 (p < 0.001) but was not different from that in group 2. Mean plasma MDA value in group 2 was significantly lower than that in group 4 (p = 0.002). Mean plasma TAS value in group 1 was significantly lower than in groups 3 (p < 0.002) and 4 (p < 0.05). Mean plasma TAS value was significantly lower in group 2 than in group 4 (p<0.05). Plasma MDA values in the diabetic patients (groups 1+2+3) were not related to any clinical characteristics (BMI, age, duration of the disease) or metabolic parameters (glycemia, HbA1c bicarbonates, blood urea nitrogen, phosphatemia, lipids), while plasma TAS values correlated negatively with glycemia, osmolality and HbA1c. A significant relationship was also found between TAS and HbA1c in group 1 (p < 0.05) and between MDA and HbA1c in group 3 (p < 0.05). Correlations were also found between TAS and phosphatemia in group 1 (p < 0.01) and between MDA and phosphatemia in group 2 (p < 0.01). A positive relationship between MDA and cholesterol levels was found in group 1 (p < 0.01). In conclusion, MDA values are increased and TAS values decreased in DKA and poorly controlled diabetes, and tend to correlate more with markers of diabetic imbalance than with markers of acute metabolic disturbances of DKA. PMID- 11194707 TI - Growth promoting effect of human plasma ultrafiltrate bioactive fraction (TBP) for human non-functioning pituitary adenoma cells in vitro. AB - We described before that the chromatographically purified "human plasma ultrafiltrate bioactive fraction" (humoral factor tentatively denoted as tumor basic protein--TBP) regulates in vitro release of ACTH from pituitary adenomas stimulating the hormone release from the tumors showing low hormonal activity in vitro and inhibiting ACTH production in vitro by highly hormonally active pituitary tumors. In this study we describe growth promoting effects (determined by 3H-TdR incorporation assay) of TBP (5 microg/l, i.e. 10% w/v plasma equivalent concentration) for 10 non-functioning pituitary tumors. The effects of TBP appeared to negatively correlate with the in vitro growth abilities of the tumors that were otherwise dependent on the duration of the clinical symptoms of the tumor presence. Hence, similar to its effects on hormonal activity of the pituitary tumors, TBP stimulated the growth of the tumors which did not express high spontaneous 3H-TdR intensity, but did not stimulate the cells with high capacity of spontaneous 3H-TdR incorporation. Moreover, all the tumors that were stimulated by TBP were nononcocytic adenomas while oncocytoma cells were not stimulated at all. Thus, TBP shows activity of humoral (plasma) factor involved in the growth regulation of pituitary adenomas that might be used to define the growth abilities of these tumors, especially in case of null cell adenomas and oncocytomas as were the tumors used in this study. PMID- 11194708 TI - Pyridostigmine and metoclopramide do not restore the TSH response to TRH inhibited by L-thyroxine treatment in children with goiter. AB - To define the role of somatostatin and dopamine in TSH suppression induced by L thyroxine, 16 children (12 F, 4 M) on suppressive doses of L-thyroxine (3-4 microg/kg/day) for endemic goiter were studied. Firstly a conventional TRH test was performed in all subjects, in order to evaluate TSH, PRL and GH (basal study). A week later a second TRH test was carried out; one hour before the test, however, group A (9 patients) was given 60 mg pyridostigmine bromide po (pyridostigmine study) and group B (7 patients) 10 mg metoclopramide po (metoclopramide study). In the basal study, TSH was suppressed in both groups and levels did not increase following TRH administration, while PRL increased significantly and GH levels remained stable. In the pyridostigmine study, TSH levels did not increase following TRH administration, while PRL and GH levels were both significantly raised. In the metoclopramide study, TSH and GH levels were not raised following TRH administration, while a significantly greater increase of PRL was observed. In conclusion, suppressive doses of L-thyroxine inhibit the TSH response to TRH, while they do not seem to affect GH and PRL secretion. Somatostatin and/or dopamine do not seem to play a significant role in the L-thyroxine-induced TSH suppression. PMID- 11194709 TI - Proteolytic processing of human growth hormone (GH) by rat tissues in vitro: influence of sex and age. AB - Although a wealth of evidence exists indicating that proteolytic cleavage can enhance the biological activity of the growth hormone (GH) molecule, the mechanisms responsible for the generation of GH fragments are not completely understood. In the present work we investigated the ability of different rat tissues to cleave 22 kDa GH, as well as the influence of sex and age, the two major physiological regulators of GH secretion on this process. Our results show that tissue homogenates obtained from rat liver, skeletal muscle or adipose tissue (three well-documented target organs for the hormone) are able to cleave 22K-GH, while the hormone is resistant to cleavage by rat brain homogenates. This process is rather selective for 22K-GH, since the 20 kDa GH variant exhibits stability to degradation by all tissue homogenates investigated. Moreover, only a minor fraction of 22 kDa GH is cleaved under our experimental conditions, suggesting that GH microheterogeneity within the 22 kDa range may also determine hormone susceptibility. Finally, we also found that 22K-GH processing shows important age-related changes (the greatest intensity observed in 4-day-old pups), while no gender-related differences exist in any of the tissues investigated. PMID- 11194710 TI - A multimodality therapeutic approach in anaplastic thyroid carcinoma: study on 39 patients. AB - The aim of this study was to investigate the role of multimodality treatment in patients with anaplastic thyroid carcinoma. From 1992 to 1999, 39 consecutive patients with a histologically or cytologically proven anaplastic thyroid carcinoma were referred to the Thyroid Center of Padua General Hospital. There were 28 females and 11 males with a median age of 69 years (range 39-88 years). About one-third of patients had a history of preceeding nodular goiter. Two patients had areas of differentiated thyroid carcinoma at histological examination. Local disease was present in 26 patients while distant metastases, mainly to the lung, were present in 22 at diagnosis or quickly developed during the observation period in all the others except one. Thirty-two patients were previously untreated: 9 of them were in good general condition, 1 had limited lung metastases, and the tumor mass was considered resectable by the surgeon. These 9 patients were treated with cisplatin once a week and radiotherapy (RT) 36Gy in 18 fractions over three weeks, followed by total thyroidectomy (TT) and by further chemotherapy (CHT) with adriamycin and bleomycin in 4 patients. Seven patients, 3 with lung metastases at diagnosis, had undergone TT, followed by RT in 5, in another hospital and were subsequently referred to our center due to the presence of distant metastases. Therefore, a total of 16 patients (Group 1) was treated with TT, RT and CHT in various order. Nine patients with distant metastases at diagnosis (Group 2) received CHT; one of them had a disappearance of lung metastases and was then treated by TT and further CHT. Group 3 consisted of 14 elderly patients in poor general conditions; 4 of these received local RT, while the remaining did not receive any treatment. Four complete responses were seen in patients from Group 1, and 1 from Group 2. One patient without distant metastases at diagnosis is alive and free of disease 6 months after TT and adjuvant CHT, and 12 months after diagnosis. Three had long-term survival (14, 24, 27 months) with a disease-free interval of 6-8-10 months. The patient from Group 2 who was treated in a second time by TT is alive without disease after 60 months. Median survival rate was 11 months for Group 1, 5.7 months for Group 2 and 4 months for Group 3. In some patients multimodality treatment (TT, RT and CHT) is associated with increased survival. Nine out of 16 patients, who underwent surgery and complementary treatment, had no local progression. In all but one distant metastases developed, mainly in the lung, during or after post surgical CHT. The best results were obtained in younger patients with less advanced disease. Early diagnosis is mandatory. Only a few patients responded to CHT, confirming that anaplastic thyroid carcinoma is often resistant to anticancer drugs. Our experience with combination modalities suggests that aggressive and appropriate combinations of RT, TT and CHT may provide some benefit in patients with anaplastic thyroid carcinoma. Preoperative CHT and RT may enhance surgical resectability of the primary tumor. PMID- 11194711 TI - Amyloid goiter in a case of systemic amyloidosis secondary to ankylosing spondylitis. AB - Infiltrative diseases of the thyroid include systemic sclerosis, hemochromatosis, sarcoidosis, chondrocalcinosis and amyloidosis. Only rarely does thyroid amyloidosis result in clinically palpable goiter. Classically, amyloidosis is associated with tuberculosis, rheumatoid arthritis, multiple myeloma or inflammatory bowel disease. Only rarely does clinical amyloidosis develop in the setting of ankylosing spondylitis. We describe a case of amyloid goiter in a patient with ankylosing spondylitis-associated amyloidosis. PMID- 11194712 TI - Use of the dopamine agonists bromocriptine and cabergoline in the management of risperidone-induced hyperprolactinemia in patients with psychotic disorders. AB - Risperidone is a novel antipsychotic agent that blocks both dopaminergic and serotonergic receptors. In several reports, clinically significant hyperprolactinemia has been reported in patients on this agent. However, the optimal management of risperidone-induced hyperprolactinemia has not been clarified. We reviewed the records of 5 patients with psychotic disorders who were evaluated for risperidone-induced hyperprolactinemia. There were 4 females and 1 male patient, aged 30-45 yr. All patients had significant hyperprolactinemia, with prolactin (PRL) levels ranging from 65.5 to 209 microg/l. All but 1 of these patients had manifestations of hypogonadism. In these 4 patients, risperidone therapy was continued and the dopamine agonists bromocriptine or cabergoline were added. In 3 out of 4 patients, such additional therapy reduced the PRL level and alleviated hypogonadism. None of the patients treated with these agents had a worsening of psychosis. We conclude that risperidone can cause clinically significant hyperprolactinemia in patients treated with this drug. If risperidone therapy must be continued in such patients, addition of the dopamine agonists bromocriptine or cabergoline may successfully alleviate hyperprolactinemia and the associated manifestations without worsening psychotic symptoms. PMID- 11194714 TI - DHEA: A forgettable steroid? PMID- 11194713 TI - Occupational and environmental agents as endocrine disruptors: experimental and human evidence. AB - In the last few years great concern has arisen from the description of adverse endocrine effects of several occupational and environmental chemical agents on human and/or wildlife health. Such agents may exert their effects directly, specifically binding to hormone receptors, and/or indirectly, by altering the structure of endocrine glands and/or synthesis, release, transport, metabolism or action of endogenous hormones. Many studies have been focused on the outcomes of the exposure to those chemicals mimicking estrogenic or androgenic actions. Nonetheless, the disruption of other hormonal pathways is not negligible. This paper reviews the experimental and human evidence of the effects of occupational and environmental chemical agents on hypothalamus-pituitary unit, pineal gland, parathyroid and calcium metabolism and adrenal glands. PMID- 11194715 TI - Animal welfare and scientific evidence. PMID- 11194716 TI - Egg safety more important than hen housing. PMID- 11194717 TI - "Extreme upset"--AVA's welfare claims appalling. PMID- 11194718 TI - President started well but now seems 'lost'. PMID- 11194719 TI - Mastitis, polyarthritis and abortion caused by Mycoplasma species bovine group 7 in dairy cattle. AB - OBJECTIVE: To report an outbreak of mastitis, polyarthritis and abortion caused by Mycoplasma sp bovine group 7 in three large, centrally-managed dairies and to review the relevant literature. DESIGN: Epidemiological, clinical and laboratory data were analysed, collated and reported. Multidisciplinary procedures were employed. These included clinical assessment and comprehensive laboratory investigations of affected calves, aborted foetuses and milk samples. Mycoplasma cultures and genetic analyses of isolates were undertaken to identify the aetiological agent. RESULTS: About 30% of 240 calves usually kept in a calf rearing facility developed severe polyarthritis as a result of Mycoplasma sp bovine group 7 infection between 2 and 3 weeks of age. Multiple abortions occurred on these farms. Mycoplasma sp bovine group 7 was recovered from the fibrinopurulent synovial exudates of four 14-day-old calves, from the stomach contents and lungs of two aborted foetuses, from 14 of 21 bulk milk and four of 10 mastitic quarters. Three bulk colostrum samples cultured during the outbreak were negative for mycoplasma. CONCLUSION: Mycoplasma sp bovine group 7 caused significant economic losses as a result of polyarthritis, abortion and mastitis. The disease probably originated from udder infections with spread being facilitated by the decreased use of tetracycline in the treatment of mastitis. Neonatal calves were most likely infected by the consumption of milk contaminated with the organism. Abortions presumably resulted from mycoplasmaemia. This appears to be the first report in Australia of bovine abortion resulting from Mycoplasma sp infection. PMID- 11194720 TI - Physical, chemical and biological hazards in veterinary practice. AB - OBJECTIVE: To identify major occupational hazards encountered by veterinarians and their staff in practice in Australia. PROCEDURE: A literature search of Medical (MEDLINE), Occupational Health and Safety (OSHRAM) and Nursing and Allied Health (CINAHL) electronic data bases plus continual monitoring utilising the Uncover alerting system using the key words, 'occupational injury', 'occupational disease' and 'safety' linked with use of the word 'veterinarians' has found relevant articles. Personal communication with people who have undertaken studies on occupational safety in veterinarians elicited further information. CONCLUSION AND RECOMMENDATIONS: Veterinarians often sustain animal-related injuries, the most common of which are dog and cat bites, cat scratches and being hit or crushed by large animals. The most costly to treat include strains and back injuries. Most veterinarians treat themselves. There is no single reporting system for injuries or disease in veterinarians and reported cases may greatly underestimate the total. There is a need to assess accurately the occupational hazards in veterinary practice, to determine the actual occurrence of injuries and to develop strategies to prevent them. PMID- 11194721 TI - Characterisation of isolates of Haemophilus paragallinarum from Indonesia. AB - OBJECTIVE: To characterise 18 isolates of Haemophilus paragallinarum isolated from chickens in Indonesia. PROCEDURE: The isolates were identified to species level by traditional phenotypic methods. Six of the isolates were also identified by a species-specific polymerase chain reaction. Fourteen of the isolates were examined for resistance to a panel of seven antimicrobial agents using a disc diffusion method. All 18 isolates were serotyped according to the Page scheme using reference antisera in a haemagglutination inhibition test. RESULTS: Four of the 18 isolates were obtained from indigenous (kampung) chickens, with the remainder being from typical intensive poultry production systems. The 18 isolates were obtained from 11 outbreaks that showed the typical clinical signs of infectious coryza and 11 of the isolates were obtained from chickens that had been vaccinated with infectious coryza vaccines. All 18 isolates were confirmed as H paragallinarum by biochemical testing and six isolates were also identified as H paragallinarum by the polymerase chain reaction test. Eleven isolates were resistant to erythromycin and streptomycin, 10 to neomycin, eight to oxytetracycline, five isolates to doxycycline, three to sulphamethoxazoltrimethoprim but only one to ampicillin. Seven isolates were Page serovar A, four were Page serovar B and seven were Page serovar C. CONCLUSION: The presence of all three Page serovars (A, B and C) has been confirmed for the first time in Indonesian chickens. As the majority of the infectious coryza vaccines in use in Indonesia contain only serovar A and C, the presence of serovar B in chickens indicates that the protection by these bivalent vaccines would be reduced. The use of trivalent infectious coryza vaccines that contain serovars A, B and C is recommended for use in Indonesia. PMID- 11194722 TI - A clinical trial to evaluate the effectiveness of antibiotic treatment of lactating cows with high somatic cell counts in their milk. AB - OBJECTIVE: To determine the effectiveness of treatment of lactating cows with high somatic cell counts in milk. DESIGN: Randomised clinical trial. METHODS: Single pooled quarter samples of milk were obtained from cows with somatic cell counts above 500,000 cells/mL on fifty farms. Milk samples were cultured for known mastitis bacterial pathogens. Cows were randomly allocated to treated and untreated groups. Treated cows received both intramammary cloxacillin and parenteral erythromycin. Single pooled quarter milk samples were obtained at 6 weeks after treatment and were cultured for the presence of pathogenic bacteria. The percentage of samples with no growth at the post-treatment culture was used as an estimate of the bacteriological cures for each pathogen type and for each treatment group. Somatic cell counts of cows were compared between treatment groups and within pathogen group. The number of cows that completed a full lactation were compared between each treatment group and within each pathogen group. RESULTS: Treatment had no effect upon bacteriological cures, irrespective of pathogen present or the presence of bacteria during the previous lactation. There was no effect of treatment upon somatic cell count except for cows infected with Streptococcus dysgalactiae in which treatment caused a significant lowering of cell counts. This effect was not present in the subsequent lactation. Treatment of chronically infected cows did not alter the probability of a cow completing a full lactation but did improve the probability of newly infected cows being retained for the next lactation. Twenty-eight of 214 treated cows developed clinical mastitis in more than one quarter after treatment, thus indicating a poor technique by farmers for the insertion of intramammary antibiotics. CONCLUSIONS: Treatment during lactation of cows with high somatic cell counts in milk is ineffective in reducing bacterial infections and in reducing somatic cell counts to acceptable numbers. PMID- 11194723 TI - Prevalence of laryngeal paresis in dogs undergoing general anaesthesia. AB - OBJECTIVE: To estimate the prevalence of laryngeal paresis within a selected population of dogs and identify some of the distinguishing characteristics of affected dogs. DESIGN: A prospective study involving laryngoscopic examination of 250 dogs. PROCEDURE: The laryngeal movements of 250 dogs undergoing general anaesthesia were observed. The severity of laryngeal paresis in these dogs was graded (0 = normal laryngeal movements, 4 = bilateral laryngeal paralysis). The following information was also recorded for each dog: age, sex, weight, breed, condition score, anaesthetic protocol, clinical suspicion of disease and observer. RESULTS: Twenty five percent of the dogs examined had some degree of laryngeal paresis. Affected dogs were significantly older than unaffected dogs (P < 0.001). There was a trend for the severity of laryngeal paresis to increase with age. There was no difference between the sexes. Dogs with laryngeal paresis were significantly heavier than normal animals (P < 0.02). Overweight animals had a significantly higher laryngeal grade than those with a normal condition score (P < 0.05). Labrador Retrievers and Rottweilers had a significantly higher risk of having laryngeal paresis (P < 0.05). Clinical suspicion was found to have high diagnostic value. An intra-class correlation coefficient for inter-rater reliability between the two observers was 0.95. CONCLUSIONS: Laryngeal paresis had a high prevalence in the animals surveyed and was strongly associated with age and breed. The results of this study are consistent with the concept of a progressive degenerative disease with a breed susceptibility. Clinical suspicion for the presence of the disease was a reliable indicator. The grading system used had a high degree of inter-observer agreement. PMID- 11194724 TI - Genetic screening for progressive retinal atrophy in the Australian population of Irish Setters. AB - OBJECTIVE: To determine whether the rcd-1 mutation causing progressive retinal atrophy (PRA) in Irish Setters is in the Australian breeding population. METHOD: DNA samples were tested for the mutation using the Polymerase Chain Reaction and specific primer nucleotides to amplify the phosphodiesterase gene followed by restriction enzyme cleavage and fragment size determination. RESULTS: No mutant alleles were found in 38 Irish Setters, representing over 80% of all major breeding stock in five Australian states. CONCLUSIONS: It is likely that the Australian population of Irish Setters is free of the rcd-1 form of PRA. PMID- 11194725 TI - Evaluation of brain damage resulting from penetrating and non-penetrating captive bolt stunning using lambs. AB - OBJECTIVE: To compare the brain damage in sheep resulting from penetrating and non-penetrating captive bolt stunning. DESIGN: The unrestrained heads of anaesthetised lambs were impacted in the temporal region with penetrating and non penetrating captive bolt pistols (humane stunners) using a constant charge. Two hours after head impact, brains were perfusion-fixed with 4% paraformaldehyde. Coronal sections were stained with haematoxylin and eosin and immunohistochemically for amyloid precursor protein, a sensitive marker of axonal and neuronal reaction in brains after trauma. Pathological changes in these brains were then quantified by morphometric analysis. RESULTS: The skull was fractured in 50% of lambs after a non-penetrating head impact and in all animals after a penetrating head wound. Impact contusions were present in 80% of lambs receiving a non-penetrating head injury and in all of those with a penetrating wound. Total contusion area was similar in both groups. Amyloid precursor protein positive axons and neurons, and haemorrhage, were widely distributed in the brain after both head impact types, but there was no statistically significant difference between the two groups. Multifocal necrosis of the cerebellar granular layer was found in all lambs with non-penetrating head injury, but in none with a penetrating injury. CONCLUSIONS: The structural brain damage, a mixture of focal and diffuse injury, produced by penetrating and non-penetrating captive bolt pistols was overall similar and of sufficient severity to suggest that both types of weapon are acceptable for euthanasia. PMID- 11194726 TI - Comparison of three serological tests and an interferon-gamma assay for the diagnosis of paratuberculosis in experimentally infected sheep. AB - OBJECTIVE: To compare the diagnostic performance of a complement fixation test, an agar gel immunodiffusion test, an enzyme-linked immunosorbent assay, and a whole-blood interferon-gamma assay for paratuberculosis in 14 sheep experimentally infected with Mycobacterium avium subsp paratuberculosis. EXPERIMENTAL DESIGN: Longitudinal study. RESULTS: The IFN-gamma assay detected more experimentally infected sheep, and earlier, than any of the serological tests. None of the antibody assays was able to detect all sheep with histologically confirmed paratuberculosis. CONCLUSIONS: The superior performance of the IFN-gamma assay in detecting infected sheep in this small experimental population warrants its further evaluation in a larger population of sheep naturally exposed to M a paratuberculosis. PMID- 11194727 TI - Improving the predictability of performance by prerace detection of dorsal metacarpal disease in thoroughbred racehorses. PMID- 11194728 TI - Bulk milk cell counts and bacterial dermatoses. PMID- 11194729 TI - Helicobacter pylori: changing patterns of ulcer disease and antibiotic resistance. PMID- 11194730 TI - Getting to grips with heroin and other opioid use. PMID- 11194731 TI - Lessons from the MONICA Project. MONItoring Trends and Determinants of CArdiovascular Disease. PMID- 11194732 TI - Domestic violence. PMID- 11194733 TI - Demographic and endoscopic characteristics of patients with Helicobacter pylori positive and negative peptic ulcer disease. AB - OBJECTIVE: To identify demographic and endoscopic characteristics of patients with Helicobacter pylori positive and negative chronic peptic ulcer disease. DESIGN: Cross-sectional study of peptic ulcer disease in prospectively recruited PATIENTS undergoing gastroscopy. PATIENTS: 277 consecutive patients referred for gastroscopy in 1996-1998. MAIN OUTCOME MEASURES: Rapid urease test, culture and histological examination for H. pylori infection; anti-H. pylori IgG antibodies in serum; demographic data, intake of non-steroidal anti-inflammatory drugs (NSAIDs) in the preceding 3 months, and size, number and location of ulcers. RESULTS: 54 patients (19%) had evidence of peptic ulcer disease (34 gastric ulcer, 14 duodenal ulcer and 6 both gastric and duodenal ulcer); 45 had active chronic peptic ulcer disease and were analysed in detail. H. pylori was present in 25 (56%) of these patients; 10 (22%) had used NSAIDs and 7 of the NSAID group also had H. pylori infection. Of the patients with gastric ulcers, those with non H. pylori, non-NSAID ulcers were significantly younger than both those with H. pylori-associated ulcers (mean age, 48 v. 65 years, P = 0.02) and those with NSAID-associated ulcers (mean age, 48 v 68 years, P = 0.02). The average size and number of gastric ulcers did not differ between patients with and without H. pylori infection. Of patients with duodenal ulcers, those with H. pylori infection had significantly fewer ulcers (1.1 v. 1.8, P = 0.04), although ulcer size was similar in the infected and uninfected groups. CONCLUSIONS: Gastric ulcers may now be more common than duodenal ulcers. Gastric ulcers associated with H. pylori infection and/or NSAID use occurred mostly in older people, while non-H. pylori, non-NSAID gastric ulcers were more common in younger patients. In the duodenum, single ulcers were associated with H. pylori infection, and multiple ulcers were more frequent in the non-H. pylori, non-NSAID group. PMID- 11194734 TI - Antibiotic resistance in Helicobacter pylori. AB - OBJECTIVE: To describe antibiotic resistance patterns in Helicobacter pylori. DESIGN: Culture and antibiotic sensitivity testing of antral and gastric body biopsy samples from patients having gastroscopy. PARTICIPANTS: Consecutive consenting patients aged 18 years or more presenting for gastroscopy from 1 July 1998 to 30 June 1999. SETTING: An open-access gastroscopy service at an urban university tertiary hospital. MAIN OUTCOME MEASURES: Number of H. pylori isolates showing resistance to antibiotics; correlates of such resistance with demographic and clinical information. RESULTS: Of 1580 patients undergoing endoscopy, 434 agreed to participate in the study. 108 (24.9%) had positive cultures for H. pylori, and 88 of these isolates (81%) were available for further testing. Resistance to metronidazole and clarithromycin was detected in 36% and 11%, respectively. No resistance was found to tetracycline or amoxycillin. Metronidazole resistance was commoner in younger patients (P = 0.0004) and macrolide resistance was commoner in those born outside Australia or New Zealand (P = 0.03). CONCLUSIONS: We found substantial resistance to metronidazole, and emerging clarithromycin resistance, but complete susceptibility to amoxycillin, tetracycline, gentamicin and cefaclor. These factors may influence the effectiveness of presently recommended eradication regimens. PMID- 11194735 TI - Trends in licit opioid use in Australia, 1984-1998: comparative analysis of international and jurisdictional data. AB - OBJECTIVES: To examine trends from 1984 to 1998 in licit opioids used in Australia compared with nine other developed countries, and in New South Wales compared with other Australian jurisdictions. DESIGN: Poisson regression analysis of annual rates of national and jurisdictional consumption of methadone, morphine and pethidine. MAIN OUTCOME MEASURES: All drug data were standardised to defined daily doses per 1000 population per day. RESULTS: Methadone consumption increased by, on average, 12% per year (RR, 1.12; 95% CI, 1.08-1.17), with Australia in the first rank of countries. Morphine use increased by 5% per year (RR, 1.05; 95% CI, 1.02-1.09), with Australia ranking equal second with three other countries behind Denmark. Consumption of pethidine in all 10 countries was unchanged (RR, 0.99; 95% CI, 0.97-1.00), with Australia equal first. In Australia, use of methadone syrup increased by 17% per year (RR, 1.17; 95% CI, 1.16-1.17) and by 11% per year for methadone tablets (RR, 1.11; 95% CI, 1.10-1.12). Consumption of methadone syrup in NSW was more than double that of any other jurisdiction. Consumption of methadone tablets was 2.4 times higher in South Australia (RR, 2.35; 95% CI, 2.09 2.65) than NSW. The Northern Territory, Tasmania and Queensland also had significantly higher consumption than NSW. From 1991 to 1998, controlled-release morphine consumption increased by 27% per year nationally (RR, 1.27; 95% CI, 1.24 1.30). The NT had 2.6 times more supply of morphine (RR, 2.63; 95% CI, 1.71-4.03) and Tasmania 58% more supply than NSW (RR, 1.58; 95% CI, 1.11-2.25). CONCLUSIONS: Australia's consumption of licit opioids ranked high internationally. There were diverse trends in the supply of licit opioids to Australia's jurisdictions, resulting in a heterogeneous pattern throughout the country. PMID- 11194736 TI - How many dependent heroin users are there in Australia? AB - OBJECTIVE: To estimate the prevalence of dependent or daily heroin users in Australia, and to compare the prevalence in Australia with that in other developed countries. DESIGN: We applied three different methods of estimation (back-projection, capture-recapture, and multiplier) to data on national opioid overdose deaths in Australia, first-time entrants to methadone maintenance treatment, and heroin-related arrests in New South Wales. We compared our estimates with estimates derived by similar methods in countries of the European Union. DATA SOURCES: Data on national opioid overdose deaths were obtained from the Australian Bureau of Statistics. Data on methadone entrants in NSW were extracted from a database maintained by the NSW Department of Health. Data on arrests for heroin-related offences were supplied by the NSW Police Service. RESULTS: The best estimates of the number of dependent heroin users in Australia in 1997-1998 from the three methods of estimation were between 67 000 and 92 000 and the median estimate was 74 000. The population prevalence was 6.9 per 1000 adults aged 15-54 years. The prevalence of heroin dependence in Australia is the same as that in Britain (7 per 1000) and within the range of recently derived estimates in the European Union (3-8 per 1000 adults aged 15-54 years). CONCLUSIONS: Although the exact figures need to be interpreted with caution, our estimates suggest that Australia has a substantial public health problem with dependent heroin use that is of a magnitude similar to that in comparable European societies. PMID- 11194737 TI - What can we do about domestic violence? AB - Domestic violence is a complex issue at both an individual and public health level. Barriers to disclosure often lie with the doctor rather than the victim. Assessment of risk and devising a safety plan are important steps for the doctor to undertake with the victim. Recommendations for joint counselling or marriage guidance for the couple are usually not appropriate. The efficacy of population screening for domestic violence has not yet been demonstrated. More limited opportunistic screening is recommended, especially in the emergency department, mental health and obstetric settings, and general practice. Health professionals can be a bridge to resources within the community, but this requires knowledge of and liaison with those services. PMID- 11194738 TI - The rediscovery of methadone for cancer pain management. AB - Methadone is a potent synthetic opioid analgesic best known in Australia as maintenance therapy for narcotic addicts. Acceptance of methadone in cancer pain management is limited by a poor understanding of its pharmacokinetics and confusion about dosage. Many opioid conversion charts underestimate the potency of methadone, resulting in the risk of toxicity. Methadone is a valuable addition to the armamentarium of clinicians treating severe cancer pain, particularly neuropathic pain, that is poorly responsive to opioids or where opioid side effects are unacceptable. PMID- 11194739 TI - Forty years of combined oral contraception: the evolution of a revolution. AB - The combined oral contraceptive (COC) pill has become an integral part of fertility choice in almost every country since its introduction in 1960 in the United States. It was the first contraceptive method to provide sexual freedom of choice for women through reliable personal, private control of fertility. Modern, very low-dose pills have maintained a high degree of contraceptive efficacy, but the margin for error in pill-taking appears much smaller. These COCs have a much lower incidence of side effects and serious complications than early high-dose COCs. Serious health risks from venous thromboembolism are rare, and not measurably higher for pills containing third-generation compared with earlier progestogens. Most women feel very well taking modern COCs, but myths about these drugs still abound. Most non-contraceptive health benefits of COCs are still not widely appreciated in spite of much evidence. Controversy still persists over the association between COC use and breast cancer. Although slightly more breast cancers are detected in current COC users (relative risk 1.24; 95% CI, 1.15 1.33), they are less advanced and less aggressive. Some women have pre-existing medical risk factors for COC use, and a detailed history for cardiovascular risk factors is one of the most important precautions. PMID- 11194740 TI - Depression: dispirited or spiritually deprived? AB - The 20th century has seen a widespread decline in mental health in Western society. One important factor may be the lack of meaning and spiritual fulfilment that is part of our increasingly secular and materialistic society. In medical education and practice, religious issues are often marginalised or 'pathologised", despite consistent evidence from the literature of the protective effect of "religiosity" or "spirituality" on mental and physical health. PMID- 11194741 TI - Pituitary apoplexy: the importance of citing the differential diagnosis. PMID- 11194742 TI - Does cleansing the birth canal at delivery reduce postnatal infection rates? PMID- 11194743 TI - Amoxycillin resistance in an isolate of Helicobacter pylori from Melbourne. PMID- 11194744 TI - Epidemic of schizophrenia in children or inappropriate prescribing? PMID- 11194745 TI - Carotid sinus massage in the elderly: is it worth the risk? PMID- 11194746 TI - Managed care. PMID- 11194747 TI - Accidental paracetamol overdosing and fulminant hepatic failure in children. PMID- 11194748 TI - Possible steroid-sparing effect in asthma of lyprinol, a shellfish lipid extract. PMID- 11194749 TI - Overcrowding and infectious diseases--when will we learn the lessons of our past? PMID- 11194750 TI - Qualitative approaches in health research. PMID- 11194751 TI - Transposition of the great arteries: operative outcome in the current era. AB - AIMS: To assess the operative outcome, cardiac and neurodevelopmental sequelae in infants with transposition of the great arteries (TGA) undergoing the arterial switch operation (ASO). METHOD: Cross-sectional review of the 48 consecutive patients operated on in the calendar years 1995 and 1996 was undertaken to obtain recent cardiac, growth and neurodevelopmental parameters, and the mortality results were compared to the entire cohort of infants who underwent the ASO for definitive repair of TGA and double outlet right ventricle at Greenlane hospital between 1984 and 1998. RESULTS: Between January 1995 and December 1996, 48 patients underwent the ASO. 96% were alive, and 88% alive and free from reoperation or significant neurological sequelae at a mean followup interval of sixteen months. Six (13%) had important residual cardiac lesions, of which supra valvular pulmonary stenosis was the most common. Growth parameters at follow-up were normal, as was the neurodevelopmental progress of all but two survivors (96%). CONCLUSION: In the current era, the ASO is a relatively safe procedure with excellent cardiac and neurodevelopmental outcome in the majority of infants. PMID- 11194752 TI - The sexual activity of 654 fourth form Hawkes Bay students. AB - AIMS: To describe the self reported patterns of sexual behaviour of 4th form High School Students from the Hawkes Bay region of New Zealand, in 1998. METHODS: Subjects completed a self administered written anonymous questionnaire in a supervised classroom situation. RESULTS: 654 4th form students, median age fourteen years, completed the questionnaire--45% male, 54% female. 39.4% of the sample reported having had sex/intercourse. Maori students were nearly three times (74.9%) as likely as European students (26.7%) to be sexually active (p < 0.0001). 20.1% of these sexually active 4th formers report more than five partners. 11.9% of the total group and 30.2% of those who are sexually active, reported having first sex at age 12 or younger. CONCLUSIONS: The sexual activity of this sample of 4th form students is higher than reported previously in New Zealand, particularly so for Maori. Further research is needed to examine sexual behaviours and attitudes of young New Zealanders in the different communities to enhance the development and provision of geographically and culturally appropriate early sexuality education programmes and services. These should be designed to have particular relevance to the needs of young Maori. PMID- 11194753 TI - The effect on medical practice of disciplinary complaints: potentially negative for patient care. AB - AIM: To explore the personal and professional effect on general practitioners (GPs) of receiving a complaint against them to the (former) Medical Practitioners Disciplinary Committee, when the complaint did not proceed to a formal hearing. METHODS: Ten GPs were interviewed by telephone, following an enrollment procedure that protected identities from the interviewer. Qualitative (thematic) analysis of indepth interviews was used to categorise doctors' perceived effects of complaints on practice and to develop a theory on why such effects should occur. RESULTS: Receipt of a complaint had both short- and long-term effects on the doctor, and on their views of patients, society and the disciplinary process. There were immediate negative emotional responses that were sustained in the long term in a way that adversely effected doctor-patient relationships beyond the relationship with the original complainant. Doctors reported short-term changes in their practice of medicine, with reduced ability to work confidently and decisively. Doctors also reported altered practice in the long-term in the direction of defensive medicine, by withdrawing from providing some services and avoiding perceived at-risk activities. CONCLUSION: The impact of a complaint on the self of the doctor suggests a shame response. There may be a need for the relevant professional college to establish a rapid response 'crash team' to minimize the negative personal and professional effects of a complaint, even when the complaint does not proceed to a formal hearing. PMID- 11194754 TI - Frequency of microdeletions in the azoospermia factor region of the Y-chromosome of New Zealand men. AB - AIM: To determine the frequency of microdeletions in the azoospermic factor (AZF) genes on the Y-chromosome of New Zealand men attending the Fertility Centre. METHODS: World Health Organisation criteria were used to classify men as normospermic, oligozoospermic, severely oligozoospermic, and azoospermic. Microdeletions were detected from DNA of semen samples by the sequence-tagged site polymerase chain reaction. RESULTS: Microdeletions were detected in 20% (3/15) of azoospermic men, 4% (2/50) of severely oligozoospermic men, 3.2% (2/62) of oligozoospermic men, and 0.7% (1/141) normospermic men. One azoospermic man had multiple non-contiguous deletions. Overall, 5.5% of infertile men had at least one microdeletion in the long arm of the Y-chromosome. One severely oligozoospermic man and one oligozoospermic man had produced unassisted pregnancies. CONCLUSION: New Zealand men attending a Christchurch fertility centre have a similar frequency of microdeletions in the Y-chromosome to other populations. Azoospermic men have a higher frequency of microdeletions than men with less severe spermatogenic failure. Men with microdeletions can have reduced fertility, but are not necessarily sterile. PMID- 11194755 TI - Concealing clinical uncertainty--the language of clinicians. PMID- 11194756 TI - Blowing the whistle on bad practice. PMID- 11194757 TI - Retention of junior medical officers. PMID- 11194758 TI - Gastrogate. PMID- 11194759 TI - Getting health back on track. PMID- 11194760 TI - Getting health back on track. PMID- 11194761 TI - Health and the World Trade Organization. PMID- 11194762 TI - Does place of residence matter? Contextual effects and smoking in Christchurch. AB - AIM: To analyse the relationship between residential segregation and smoking and quit rates in Christchurch. METHOD: The study used a nested research design, which examines the extent to which variations in adult smoking rates at the meshblock level are, when holding socio-economic status constant, also influenced by the socio-economic profile of the census area units or wider communities within which they are located. RESULTS: Smoking and quit rates are not only related to levels of local neighbourhood (meshblock) deprivation, but also depend to a large extent on whether such neighbourhoods are located in socially segregated or more socially mixed parts of the city. The findings provide added support for the independent influence of contextual effects on smoking behaviour. CONCLUSION: The results suggest that attempts to further reduce smoking should target places as well as people. PMID- 11194763 TI - Utilisation rates in capitated primary care centres serving low income populations. AB - AIM: To measure utilisation rates in capitated primary care organisations serving low income populations with low or zero co-payments, and to examine the relationship between utilisation rates and organisation, age group, sex, ethnicity, community services card (CSC) holding rates, high use health card (HUHC) holding rates and deprivation of area of residence (NZDep96). METHODS: Data were collected during 1997/98, from eleven primary care organisations. Utilisation data were collected from practice computer information systems. RESULTS: 53.9% of registered patients were recorded as having consulted in a twelve-month period. Utilisation rates for doctor, nurse and midwife combined were higher amongst the young, elderly, and CSC holders. For males, they were higher amongst those living in the most socioeconomically deprived areas, but not for females. Utilisation rates were highest amongst the 'other' ethnic group, and lowest in the Pacific Island ethnic group. Organisation, age group, sex, ethnicity, CSC, HUHC and NZDep96 were independently predictive of total utilisation. CONCLUSIONS: Utilisation rates in capitated practices tended to be lower than those in fee-for-service practices. If equitable needs-based capitation funding formulas are to be developed, utilisation data from capitated practices in a range of cultural and socioeconomic settings is urgently required. PMID- 11194764 TI - "The view from the bottom of the cliff." Old age psychiatry services in New Zealand: the patients and the resources. AB - AIM: Despite the continual restructuring of New Zealand's health services in recent years, the development of mental health services for older people has been neglected as a strategic planning issue. METHODS: In 1998/9, the New Zealand branch of the Faculty of Psychiatry of Old Age (FPOA) of the Royal Australian and New Zealand College of Psychiatrists (RANZCP) initiated a national survey to obtain an overview of patient needs and national resources, with the aim of providing information to assist planning. Data were collected from eleven Old Age Psychiatry services nationwide, covering a total catchment of 2,800,000 New Zealanders. RESULTS: Patients were mostly over 70 years of age, female and with high co-morbidity for both medical and psychiatric illnesses. New Zealand resources directed to meet the needs are low by international standards. CONCLUSIONS: The results clarify the range of patient problems that Old Age Psychiatry services manage and the resources available. Most New Zealand services conform to World Health Organization recommendations. PMID- 11194765 TI - Distal forearm fractures in New Zealand children: annual rates in a geographically defined area. AB - AIMS: To estimate the annual incidence of distal forearm fractures in New Zealand children and to describe circumstances associated with this fracture. METHODS: The ages and dates of fracture of all girls and boys aged three to fifteen years with distal forearm fractures treated at Fracture Clinic, Dunedin Public Hospital in one calendar year were recorded. RESULTS: The age-standardised annual incidence rates for Dunedin girls and boys aged three to fifteen years were 10.4 per 1000 (95% CI 8.3-12.4 per 1000), and 10.4 per 1000 (95% CI 8.3-12.6 per 1000), respectively. The peak incidence in girls was observed at ten years of age (23.5 fractures per 1000) and for boys at thirteen years of age (25.3 fractures per 1000). Extrapolation of these rates to all New Zealand suggest that in children aged three to fifteen years, 3659 (95% CI 2906-4413) distal forearm fractures occur per year in girls, and 3845 (95% CI 3087-4603) per year in boys, representing about 20 fractures per day. Many of the fractures for the girls and boys resulted from apparently slight trauma (62.2% and 61.6%, respectively). CONCLUSIONS: Distal forearm fractures are very common events in New Zealand children and adolescents, and are usually caused by apparently slight trauma. PMID- 11194766 TI - Waiting for coronary bypass surgery. Observations from the sidelines. PMID- 11194767 TI - Whither the public health function? PMID- 11194768 TI - There is no place for a graduate entry medical course in New Zealand. PMID- 11194769 TI - Gastrogate. PMID- 11194770 TI - Getting the fat tax on the table. PMID- 11194771 TI - Pregnancies among New Zealand teenagers. PMID- 11194772 TI - Rickets in the welfare state. PMID- 11194773 TI - Re-using 'single-use' medical devices. PMID- 11194774 TI - Evolving concepts in the pathogenesis of chronic obstructive pulmonary disease. AB - It is arguable that more biologic insight has been gained from the study of COPD than from any other pulmonary disorder. A vast knowledge of the biology of extracellular matrix proteins, proteinases, and proteinase inhibitors has largely stemmed from the elastase:anti-elastase hypothesis for the pathogenesis of emphysema. An equally compelling case could be made that interest in, and funding for, COPD research has been woeful, and investigators have made no significant medical breakthroughs in the treatment of this disorder, which, unfortunately, is becoming epidemic worldwide. Indeed, it cannot be argued that physicians have very little treatment to offer to the many patients with COPD. Humankind is rapidly approaching a time when all human genes will be sequenced, and genetic engineering will allow determination of the function of these proteins in vivo. Expression profiling and bioinformatics will allow clinicians to assess the spectrum of genes and proteins regulated in biologic processes, no longer limiting study to naive candidate genes. These advances will allow investigators to decipher precise pathways of complex diseases, identify genetic and environmental interactions, and ultimately lead to specific (pre)diagnoses and rational treatment. Answers to the question as to why only a subset of smokers develop COPD will enhance the understanding of the disease process. Fortunately, there has been a resurgence of interest in COPD, led largely by the pharmaceutical industry, which has discovered the potential of this unmet need. Consequently, these state-of-the-art scientific techniques are being directly applied to COPD, lending hope for the future. Of even greater importance, the tide seems to be turning on the cigarette industry. Although difficult to imagine, perhaps cigarettes will disappear in this lifetime or at least the next generation won't be fooled by this deadly habit! Well ... the rational therapy thing could work. PMID- 11194775 TI - Genetic risk factors for chronic obstructive pulmonary disease. AB - Numerous epidemiologic studies have indicated that there is a genetic basis to COPD. This result suggests that COPD develops in genetically susceptible individuals after sufficient exposure to cigarette smoke. At present, most of the genes that contribute to the genetic component to COPD are unknown. alpha 1 Antitrypsin deficiency is clearly a risk factor for COPD, but the other genetic associations with this disease must be considered as tentative. The key to establishing that a gene modifies the risk for a disease is replication of the association in different populations. This is a difficult task, however, because different genetic risk factors may be present in different populations. In addition, these genetic factors may interact with each other and with environmental risk factors, obscuring the effect of the gene on the phenotype. Apart from alpha 1-AT only the GST-M1, VDBP and CFTR genes have been implicated as risk factors in more than one population. Identification of other candidate genes awaits further understanding of the pathogenesis of COPD at the molecular level. There is good evidence that the propensity to smoke cigarettes and the likelihood of quitting smoking are influenced by genetic factors. This information may be useful in efforts directed toward cessation; however, most of the genetic studies so far have shown a rather small effect. The responses to hypoxia and hypercapnia also seem to be influenced by genetic factors. Identification of the genes involved could yield important insights into the pathogenesis of COPD and may highlight new targets for therapeutic intervention for this debilitating disease. PMID- 11194776 TI - Controversies in the use of spirometry for early recognition and diagnosis of chronic obstructive pulmonary disease in cigarette smokers. AB - Office spirometry used to detect COPD in smokers ages 44 and above with respiratory symptoms probably meets the criteria for a population-based screening test and for clinical case finding: If not detected early, COPD causes substantial morbidity or mortality, and smoking cessation is more effective when COPD is recognized before exertional dyspnea develops. Office spirometry is a feasible testing strategy and may be used to encourage smoking cessation efforts that change behavior in at least some patients. Office spirometry is relatively simple and affordable, is safe, and includes an action plan with minimal adverse effects. On the other hand, the false-positive and false-negative rates of office spirometry in the primary care setting may be higher than diagnostic spirometry performed during epidemiologic studies or in diagnostic pulmonary function laboratories, and the incremental benefit of office spirometry on smoking cessation rates is poorly established (when added to referral to an AHCPR-based smoking cessation program). PMID- 11194777 TI - Advances in radiologic assessment of chronic obstructive pulmonary disease. AB - Chest radiography allows detection of moderate and severe emphysema but does not allow quantitation of severity of disease or detection of mild emphysema. Chest radiography is helpful in assessing complications of emphysema such as pneumothorax or secondary infection of a bulla. HRCT provides a detailed image of emphysematous lung disease comparable to that of macroscopic pathologic appearance. The main role of HRCT in patients with COPD is in the preoperative assessment of patients being considered for bullectomy or LVRS. PMID- 11194778 TI - Peripheral muscle dysfunction in chronic obstructive pulmonary disease. AB - Peripheral muscle dysfunction is a common systemic complication of moderate to severe COPD and may contribute to disability, handicap, and premature mortality. In contrast to the lung impairment, which is largely irreversible, peripheral muscle dysfunction is potentially remediable with exercise training, nutritional intervention, oxygen, and anabolic drugs. Therapeutic success is often incomplete, however, and a better understanding of the mechanisms involved in the development of peripheral muscle dysfunction in COPD is needed to help develop innovative and more effective therapeutic strategies. PMID- 11194779 TI - Respiratory muscle function and drive in chronic obstructive pulmonary disease. AB - Respiratory, and particularly inspiratory, muscle function is altered in COPD. Many of these alterations are secondary to a mechanical disadvantage related to hyperinflation. Other factors, including corticosteroid therapy and nutritional depletion, are also deleterious to muscle function. In addition, the load imposed on the respiratory muscles is increased in COPD. Combined with the altered respiratory muscle function, this increase induces important changes in respiratory muscle drive and recruitment. Moreover, the imbalance between respiratory muscle function and load is an important determinant of dyspnea and hypercapnia. Because much of the lung and airway derangements are irreversible in COPD, the respiratory muscles appear to be an attractive target for therapeutic interventions. PMID- 11194780 TI - Mechanisms and measures of exercise intolerance in chronic obstructive pulmonary disease. AB - The mechanisms for exercise intolerance in chronic obstructive pulmonary disease are complex and multifaceted. Although ventilatory limitation caused by abnormal pulmonary function is a major contributor to this phenomenon, other factors may play an important role in limiting exercise. These other factors include depressed cardiac function, respiratory and peripheral muscle weakness, nutritional imbalances, and psychologic factors. The assessment of the pulmonary patient who complains of decreased functional status must include examination and consideration of all these variables. Only by addressing and treating the combination of these variables as they present in an individual patient will clinicians have the potential to impact that individual's functional status and quality of life. PMID- 11194781 TI - The chronic obstructive pulmonary disease exacerbation. AB - Chronic obstructive pulmonary disease is the only leading cause of death with a rising prevalence. The medical and economic costs arising from acute exacerbations of COPD are therefore expected to increase over the coming years. Although exacerbations may be initiated by multiple factors, the most common identifiable associations are with bacterial and viral infections. These are associated with approximately 50% to 70% and 20% to 30% of COPD exacerbations, respectively. In addition to smoking cessation, annual influenza vaccination is the most important method for preventing exacerbations. Controlled O2 is the most important intervention for patients with acute hypoxic respiratory failure. Evidence from randomized, controlled trials justifies the use of corticosteroids, bronchodilators (but not theophylline), noninvasive positive-pressure ventilation (in selected patients), and antibiotics, particularly for severe exacerbations. Antibiotics should be chosen according to the patient's risk for treatment failure and the potential for antibiotic resistance. In the acute setting, combined treatment with beta-agonist and anticholinergic bronchodilators is reasonable but not supported by randomized controlled studies. Physicians should identify and, when possible, correct malnutrition. Chest physiotherapy has no proven role in the management of acute exacerbations. PMID- 11194782 TI - Update on pharmacologic therapy for chronic obstructive pulmonary disease. AB - As described throughout this article, significant improvements continue to occur in the pharmacologic management of COPD. These improvements range from improved medication targeting to better understanding of mechanisms of action, to better delivery of medications, to lower side effects. New areas of pharmacologic intervention, if not ready for use today, hold great promise for the not-too distant future. In addition to the many agents described here, multiple mediator antagonists and anti-inflammatory agents are also under investigation for use in COPD. Interestingly, repair of alveolar tissue may be possible. Indeed, preliminary animal studies suggest that retinoic acid may be able to induce regeneration of lung alveoli. Overall, more effort is needed to broaden awareness and provide for the appropriate diagnosis of COPD, better explain pharmacologic therapies for COPD, simplify and disseminate guidelines, and highlight key differences between asthma and COPD, including their treatment strategies. As interest in COPD continues to grow, future updates on COPD management will continue to add new pharmacologic options for this devastating and preventable disease. PMID- 11194783 TI - Corticosteroids in chronic obstructive pulmonary disease. Clinical benefits and risks. AB - The use of systemic and inhaled corticosteroids for COPD has increased appreciably over the past 20 years. Clearer indications for corticosteroid therapy in COPD are beginning to emerge as the results from large clinical trials become available. Systemic corticosteroids are only modestly effective for acute COPD exacerbations, increase the risk for hyperglycemia, and should be given for no more than 2 weeks. The efficacy of long-term systemic corticosteroid therapy has not been adequately evaluated in this patient population. If longer term use of systemic steroids in COPD should be found to be useful, this conclusion would have to be weighed against the risk for serious adverse effects. High doses of inhaled corticosteroids cause a small sustained increase of the FEV1 in patients with mild and moderately severe COPD, but they do not slow the rate of FEV1 decline. Based on analyses of secondary outcome, inhaled corticosteroids may improve the respiratory symptoms and decrease the number and severity of COPD exacerbations in patients with more advanced disease. Low doses of inhaled corticosteroids appear to be safe, but there is growing awareness that higher doses may not be so benign. PMID- 11194784 TI - Nutritional abnormalities and supplementation in chronic obstructive pulmonary disease. AB - Weight loss and muscle wasting commonly occur in patients with chronic obstructive pulmonary disease (COPD). A decreased dietary intake and elevated energy requirements underlie weight loss in these patients. Disturbances in intermediary metabolism caused by altered anabolic and catabolic mediators such as hormones, cytokines, and growth factors, and resulting in disproportionate muscle wasting have been described. Nutritional supplementation in combination with an anabolic stimulus (e.g. exercise) has been shown effective in improving functional capacity, health status, and mortality in most depleted patients. Nutritional or pharmacologic modulation of the catabolic response may further enhance the response in the near future. PMID- 11194785 TI - Exercise training in chronic obstructive pulmonary disease. AB - Exercise limitation is a common and disturbing manifestation of COPD. The exercise intolerance is often caused by multiple interrelated anatomic and physiologic disturbances. Importantly, exercise tolerance can be improved despite the presence of fixed structural abnormalities in the lung. Exercise training, undertaken alone or in the context of comprehensive PR, improves exercise endurance and, to a lesser degree, the maximal tolerated workload of patients with COPD. Pulmonary rehabilitation also improves dyspnea and QOL. Exercise training and PR should be considered for all patients lacking contraindications who experience exercise intolerance despite optimal medical therapy. Lower extremity training should be included routinely in the exercise prescription. The choice of type and intensity of training should be based primarily on the patient's individual baseline functional status, symptoms, needs, and long-term goals. When tolerated, high-intensity (continuous or interval) training may lead to greater improvements in aerobic fitness than low-intensity training but is not absolutely necessary to achieve gains in exercise endurance. Upper-extremity training should be undertaken when possible. Ventilatory muscle training should be considered for patients who continue to experience exercise limitation and breathlessness despite medical therapy and general exercise reconditioning. Exercise tolerance may improve following exercise training because of gains in aerobic fitness or peripheral muscle strength; enhanced mechanical skill and efficiency of exercise; improvements in respiratory muscle function, breathing pattern, or lung hyperinflation; as well as reduction in anxiety, fear, and dyspnea associated with exercise. Gains made in exercise tolerance can last up to 2 years following a limited duration (6-12 week) rehabilitation program. PMID- 11194786 TI - Noninvasive ventilation in chronic obstructive pulmonary disease. AB - Over the past 15 years, numerous studies have explored the possibility that intermittent ventilatory assistance using noninvasive ventilation is beneficial in patients with severe stable COPD. The results are conflicting and no sustained beneficial action has been proven, although some improvement in respiratory muscle function may occur after short-term rest, and lengthening of the total duration of sleep has been shown in a few studies. Based on the observation that studies with favorable findings have generally had considerably higher PaCO2s than studies with negative findings, the current consensus view is that patients with severe CO2 retention (PaCO2 > 50-55 mm Hg) warrant a trial of NPPV. In addition, the Health Care Financing Agency that determines Medicare reimbursement policy in the United States has recently published guidelines for use of NPPV in patients with severe stable COPD that are based partly on the consensus view. There remains a deficiency of evidence supporting this application, however, and no study has confirmed any survival benefit or sustained improvement in functional status. Of note, several uncontrolled studies suggest that days of hospital use may be reduced after initiation of NPPV in these patients, but confirmatory studies are pending. If NPPV is to be initiated in patients with severe stable COPD, a more difficult adaptation process should be anticipated than for patients with neuromuscular disease. Great care must be taken in selecting a proper mask and optimal ventilator settings, and patients usually require considerable reassurance and encouragement. Potential problems should be anticipated and prevented, if possible. With a patient and supportive approach and a willingness to devote time to the process, clinicians can help optimize the likelihood of success, but failure rates are apt to remain higher than for other forms of chronic respiratory failure until the patient subpopulations with COPD most likely to benefit from NPPV are better defined and improvements in mask and ventilator technology enhance tolerance rates. PMID- 11194787 TI - Mechanical ventilation in chronic obstructive lung disease. AB - Exacerbations of COPD are a leading indication for MV in the intensive care unit. A thorough understanding of the pathophysiology of AVF in COPD is critical for physicians caring for these patients. In particular, physicians should understand DHI and use the ventilator and ancillary techniques to minimize its impact. Noninvasive positive-pressure ventilation should be considered strongly in relatively stable patients with an adequate mental status and manageable secretions. Once AVF resolves, patients should be removed from the ventilator as soon as is safe to do so to minimize the adverse effects of prolonged MV. An organized approach to weaning and identifying patients capable of independent breathing is crucial. Most patients with COPD and AVF benefit from MV and generally return to or approach their premorbid functional status. A significant subset, however, will not benefit from, or choose not to undergo, MV. Deciding upon appropriate therapeutic options for these patients relies heavily on effective communication between physician and patient. Comprehensive discussions before the development of AVF can assist decision-making after respiratory failure develops. PMID- 11194788 TI - Lung volume reduction surgery for emphysema. AB - Over the past decades, extensive literature has been published regarding surgical therapies for advanced COPD. Lung-volume reduction surgery would be an option for a significantly larger number of patients than classic bullectomy or lung transplantation. Unfortunately, the initial enthusiasm has been tempered by major questions regarding the optimal surgical approach, safety, firm selection criteria, and confirmation of long-term benefits. In fact, the long-term follow up reported in patients undergoing classical bullectomy should serve to caution against unbridled enthusiasm for the indiscriminate application of LVRS. Those with the worst long-term outcome despite favourable short-term improvements after bullectomy have consistently been those with the lowest pulmonary function and significant emphysema in the remaining lung who appear remarkably similar to those being evaluated for LVRS. With this in mind, the National Heart, Lung and Blood Institute partnered with the Health Care Finance Administration to establish a multicenter, prospective, randomized study of intensive medical management, including pulmonary rehabilitation versus the same plus bilateral (by MS or VATS), known as the National Emphysema Treatment Trial. The primary objectives are to determine whether LVRS improves survival and exercise capacity. The secondary objectives will examine effects on pulmonary function and HRQL, compare surgical techniques, examine selection criteria for optimal response, identify criteria to determine those who are at prohibitive surgical risk, and examine long-term cost effectiveness. It is hoped that data collected from this novel, multicenter collaboration will place the role of LVRS in a clearer perspective for the physician caring for patients with advanced emphysema. PMID- 11194789 TI - Lung transplantation for chronic obstructive pulmonary disease. AB - Lung transplantation is able to provide dramatic gains in pulmonary function to patients with advanced pulmonary emphysema. At the present time, however, transplantation is available to a strictly defined pool of candidates, and outcomes are limited by numerous respiratory and nonrespiratory postoperative complications. Further progress is needed in expanding the supply of donor lungs, minimizing perioperative complications, and optimizing postoperative immunologic management. PMID- 11194790 TI - Epidemiology of invasive and other pneumococcal disease in children in England and Wales 1996-1998. AB - The results of enhanced national surveillance of pneumococcal disease in children < 15 y of age in England and Wales are reported for the period 1996-1998. Of the 1985 cases of laboratory-confirmed invasive disease (annual incidence 6.6 per 100,000 overall and 39.7 per 100,000 in infants < 1 y of age), 485 (24%) were meningitis (annual incidence of 1.6 per 100,000 overall and 15.7 per 100,000 in infants <1 y of age). Fifty-nine deaths in children with invasive disease were identified-3% of the total reports. Thirty-one different serogroups/types were identified, with organisms in the 7-valent conjugate vaccine responsible for 69% of the infections in children < 5 y of age: this rose to 77% and 82%, respectively, for the 9-and 11-valent vaccines. Resistance to penicillin varied from 2.3% to 6.2% in different years, but erythromycin resistance remained constant at 17%. The vast majority of resistant isolates were in vaccine serotype/groups. Computerized hospital admission records for all children < 15 y of age with a discharge diagnosis code indicating probable pneumococcal disease were also analysed for 1997. The annual incidence for cases with a code specifically mentioning S. pneumoniae was 9.9 per 100,000 compared with 71.2 per 100,000 for lobar pneumonia; the mean duration of stay for both was < 1 wk. The incidence of admission for pneumococcal meningitis (1.9 overall and 19.6 for infants < 1 y of age) was similar to that derived from laboratory reports and resulted in an average duration of stay of 2 wk. CONCLUSION: This surveillance has confirmed the substantial burden of morbidity attributable to pneumococcal disease in British children and the potential public health benefits that could be achieved by the use of pneumococcal conjugate vaccines. PMID- 11194791 TI - Epidemiology of pneumococcal disease in children in Germany. AB - Recently published and as yet unpublished data allow a reasonable estimate of the annual burden of pneumococcal disease in Germany. At least 277,000 episodes of otitis media and at least 2,000 episodes of sinusitis occur in children under the age of 5 y. Pneumococcal meningitis was found in 200 children under the age of 16 y; the estimate for all age groups ranges from 450 to 1100 cases. Of approximately 150,000 cases of ambulatory pneumococcal pneumonia, at least 63,000 105,000 patients are hospitalized each year. CONCLUSION: Further studies of pneumococcal epidemiology in Germany are needed, and continued surveillance will be necessary for a better understanding of the overall burden of pneumococcal disease in children as well as adults. PMID- 11194792 TI - Epidemiology of meningitis and bacteraemia due to Streptococcus pneumoniae in The Netherlands. AB - In The Netherlands, accurate data on the epidemiology of pneumococcal meningitis are available through a clinical microbiology laboratory-based national surveillance of cerebrospinal fluid isolates. The Netherlands Reference Laboratory for Bacterial Meningitis receives isolates of about 80% of all meningitis cases and about 40% of bacteraemic cases. The incidence of pneumococcal meningitis has increased slowly from 1.0/100,000 in 1990 to 1.5/100,000 since 1996. The highest age-specific incidence of meningitis was observed in children < 5 y of age (8.2/100,000 in 1999). Of all isolates, 35% were from children < 5 y of age. The number of isolates from non-meningitis patients with bacteraemia increased considerably since the early 1990s, especially among the elderly. The highest incidence was found in 1996, probably owing to a relatively severe winter. During 1995-1999, pneumococcal meningitis in The Netherlands was caused mainly by serotypes 3, 6B, 7F, 9V, 14, 18C, 19F, and 23F. Of the cases in children < 15 y, almost half were caused by serotypes 6B, 14, 18C, and 19F. The serotypes present in the 23-valent polysaccharide and 7 valent conjugate vaccines accounted for 87% and 47% of all meningitis cases, respectively. Pneumococcal resistance to penicillin in The Netherlands is still low, at about 1%. Genotypically, resistant strains belong to many clones. Horizontal transfer of capsular genes occurs among these isolates. In The Netherlands, 45% of cases of pneumococcal meningitis have severe predisposing factors. The case-fatality rate was significantly higher among patients with impaired immunity than among those with a break in the integrity of the dura. PMID- 11194793 TI - Epidemiology of pneumococcal infections in French children. AB - Since 1977, resistance to beta-lactams and other families of antibiotics among isolates of Streptococcus pneumoniae has increased alarmingly worldwide. France is particularly affected by this phenomenon; in 1997 the French National Reference Centre for Pneumococci reported that 44% of S. pneumoniae strains were penicillin non-susceptible (PNSS). Furthermore, resistance to macrolides (53%) and sulphonamides (37%) was comparable; in addition, >50% of PNSS had a high level of resistance to penicillin and were multiresistant. The highest frequency of resistance is observed in children, particularly those with acute otitis media (AOM). CONCLUSION: The clinical consequences of increasing antibiotic resistance are evident for meningitis and AOM, prompting clinicians to consider alternative agents such as high-dose cefotaxime (300 mg/ kg/d) or ceftriaxone (100mg/kg/d) plus vancomycin (60 mg/kg/d) for meningitis, and high-dose amoxicillin (> 80 mg/kg/d) or ceftriaxone (50 mg/kg/d) for AOM. PMID- 11194794 TI - Epidemiology of invasive pneumococcal infections in children aged 0-6 years in Denmark: a 19-year nationwide surveillance study. AB - The impact of the new pneumococcal conjugate vaccines on invasive disease burden in Danish children was evaluated by analysing the results from the last 19 years of a nationwide surveillance of invasive pneumococcal infections. During 1981 1999, the Streptococcus Unit at Statens Serum Institut, Copenhagen, received 1123 invasive pneumococcal isolates from children aged 0-6 years. Nearly 72% (71.8%) of the pneumococcal isolates were from children aged <2 y. The median ages of children with pneumococcal meningitis and bacteraemia were 10.2 mo and 15.9 mo, respectively. The incidence of pneumococcal meningitis remained stable during the study period. The mean annual incidence rates of pneumococcal meningitis among children aged <1, <2, and <7 years were 17.4, 12.4, and 4.3 per 100,000, respectively, during 1981-1999 (overlapping age groups are used throughout this article to facilitate the comparison of incidence data from different countries or among different studies). The annual incidence of pneumococcal bacteraemia increased from 1981 to 1996, after which a slight fall was noted. During the last six years of the study period, the mean annual incidence rates of bacteraemia were 30.1, 32.5, and 14.0 per 100,000 children aged < 1, < 2, and < 7 years. In the 1990s, pneumococcal isolates with reduced sensitivity to penicillin (0-5% each year) and erythromycin (7.4% in 1999) emerged as a cause of invasive infections in children aged 0-6 years in Denmark. During 1981-1999, 10 serotypes (1, 4, 6A, 6B, 7F, 9V, 14, 18C, 19F, 23F) caused 82% of invasive infections in Danish children. Importantly, no significant temporal changes in overall serotype distribution or differences in serotype distributions between girls and boys could be documented during the study period. CONCLUSION: According to the Kaiser Permanente trial, the 7-, 9-, and 11-valent pneumococcal conjugate vaccines will probably cover around 60%, 70%, and 80%, respectively, of all invasive pneumococcal infections in Danish children aged 0-6y, corresponding to 12-14 episodes of meningitis and 40-60 episodes of bacteraemia per year. PMID- 11194795 TI - Epidemiology of invasive childhood pneumococcal infections in Greece. AB - A retrospective study was conducted to identify the epidemiologic characteristics of invasive pneumococcal infections among children <14 y of age in our geographic region. During a 5-y period, from 1995 to 1999, 590 cases of invasive pneumococcal infection were identified in Aghia Sophia Children's Hospital, Athens, Greece. The male to female ratio was 1.4:1 and 64% of patients were younger than 5 y of age. The overall annual incidence rate was estimated as 44/100,000 children <14y of age, whereas the incidence rate for children <5y of age was 100/100,000. The most common types of infections were pneumonia (472 cases; 133 definite and 339 probable), bacteraemia without focus (79 cases), and meningitis (33 cases). A seasonal variation of invasive pneumococcal infections was noted, with two peaks--one during spring and the other during autumn. Only two cases with meningitis died and one developed permanent neurological sequelae, representing a case-fatality rate for meningitis of 6%. Serogroups 14, 19, 6, 18, 23, 4 and 9 were the most prevalent, comprising 77% of 92 serotyped isolates. CONCLUSION: Invasive pneumococcal infections cause considerable morbidity in the paediatric population in the Athens metropolitan area. Sixty-six percent of the serotypes causing invasive pneumococcal disease in our region are included in the 7-valent conjugate vaccine. PMID- 11194796 TI - Epidemiology of pneumococcal infections in Swedish children. AB - OBJECTIVE: This paper provides an overview of pneumococcal infections in Swedish children. METHOD: Data supplied by the Swedish Institute for Infectious Disease Control (SMI) provided information on invasive pneumococcal isolates and on isolates with reduced susceptibility to penicillin. Disease burden was estimated from data collected in northern Stockholm and Malmohus County. RESULTS: Only 3-6% of the total number of invasive pneumococcal isolates came from children 0-15 years of age. Predominant serotypes in descending frequency were 7, 6, 14, and 23. Strains from all sources with reduced sensitivity to penicillin (MIC > or = 0.5 mg/l) were found in 3% of children and varied between 0.2% and 11%, with the highest value found in Southern Sweden (predominating strains were 9, 19, 15, 6, and 23). A 10-year review of all cases of meningitis in Northern Stockholm reflected an incidence of 10/100,000 (0-2 years) or 5.8/100,000 (0-5 years), with severe sequelae occurring in 20% of children. This information can be used to predict an annual incidence of 30 cases of meningitis in Sweden. CONCLUSION: The large proportion of serotype 7 among invasive isolates is distressing since this serotype is not represented in the present 7- and 9-valent protein-conjugated vaccines under development. However, the heptavalent vaccine, including serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F would (at a serotype level) provide coverage against 83% of the resistant isolates in Southern Sweden. PMID- 11194797 TI - Epidemiology of Streptococcus pneumoniae in Italian children. AB - In Italy, data regarding the aetiological role, antibiotic resistance, and serotype distribution of isolates of Streptococcus pneumoniae are scarce and based on very small population samples. We found that S. pneumoniae caused about 30% of lower respiratory tract infections and 15% of acute otitis media infections in Italian children. The incidence of S. pneumoniae meningitis in subjects aged 0-4y was 1.1 x 100,000. In children <5 y of age with meningitis, the most common S. pneumoniae serotypes were, in rank order, 14, 6, 23, 1 and 4; among 53 nasopharyngeal carriers the most frequent serotypes were 6 and 19. The actual percentage of resistance of S. pneumoniae to penicillin is 10.2%, while for macrolides it reaches 25.5%. More data on the distribution of serotypes in Italian children are urgently needed in order to obtain a better understanding of the impact of the new pneumococcal vaccines. PMID- 11194798 TI - Streptococcus pneumoniae in children in Spain: 1990-1999. AB - This study analyses the serogroups/types (SGTs) and resistance to penicillin and erythromycin of 3921 strains isolated from 1990 to 1999 in children aged 0-14 y in Spanish hospitals of all the autonomous communities. Based on the age of the children, strains have been divided into five groups: 0-6 mo, > 6-1 y, > 1-2 y, > 2-5 y and > 5 y. While only eight SGTs were responsible for 80% of the infections in children from 6 mo to 2 y of age, this number increased to 11 and 16 for the groups > 2-5 y and > 5-14 y, respectively. SGTs 6, 14 and 19 were prevalent in blood and otic exudates. SGTs 1, 4, 5, 12 and 18 were more frequent in invasive disease but serotype 3 was clearly associated with otitis. Serotypes I and 5 were quite significant in children of over 2 y of age, and this should be taken into account in future vaccine formulations. CONCLUSION: Although high, the rate of penicillin resistance in the paediatric population has remained stable in recent years. Conversely, erythromycin resistance is still increasing in our country. Coverage by the 7-valent vaccine was 78 and 81% for blood and otic isolates, respectively. These coverage levels would be increased by 9% and 3% if 9-valent (plus 1 + 5 serotypes) were used and by an additional 2.6% and 7.6% using the 11 valent (plus 3 + 7) formulation. PMID- 11194799 TI - The 2000 presidential address. Back to the future: the ABA and burn prevention. PMID- 11194800 TI - The 2000 Everett Idris Evans Memorial Lecture. Burn prevention: a long way. PMID- 11194801 TI - The 2000 Clinical Research Award. Describing and predicting distress and satisfaction with life for burn survivors. AB - We investigated ratings of emotional distress and satisfaction with life at discharge from the hospital and at a 6-month follow-up in a multisite sample of 295 adults hospitalized for the care of a major burn injury. Several psychosocial variables (history of alcohol abuse, marital status, and previous mental health) and some medical variables (days of intensive care, pulmonary complications, and hand burns) accounted for significant variance in the prediction of outcomes. Brief Symptom Inventory (distress) scores were higher and Satisfaction With Life Scale scores were significantly lower than those of a normative population at both measurement points. The results show the utility of biosocial models in which psychological and physical variables interact to influence adjustment and quality of life. PMID- 11194802 TI - The 2000 Moyer Award. The relevance of base deficits after burn injuries. AB - The relevance of an elevated base deficit (BD) during the fluid resuscitation of a thermally injured patient is not completely understood. After nonthermal trauma, early elevation of the BD represents insufficient cellular perfusion and is ultimately associated with a higher incidence of organ dysfunction and death. However, this relationship has not been completely examined after burn injuries. The purpose of this study was to determine if elevation of the BD during burn resuscitation was associated with potential consequences of malperfusion, such as systemic inflammatory response syndrome, acute respiratory distress syndrome, and multiple organ dysfunction. The records of 72 patients with burn injuries (mean age, 46 +/- 17 years; mean total body surface area burned, 44% +/- 18%) who required fluid resuscitation on admission to an adult regional burn center were analyzed. Patients with a mean BD of less than -6 mmol/L during the first 24 hours were compared with patients with a mean BD of more than -6 mmol/L. Despite adequate resuscitation with good maintenance of urinary output, the patients in the group with a mean BD of less than -6 mmol/L had more florid systemic inflammatory response syndrome (P = .004), had more prevalent acute respiratory distress syndrome (P = .012), and experienced more severe multiple organ dysfunction (P < .001) compared with patients in the group with a mean BD of more than -6 mmol/L. The results suggest that abnormal elevation of the BD after burn injuries represents a malperfusion state, which may not be recognized if only "traditional" parameters, such as UO, are followed. Furthermore, this state appears to be related to the onset of more severe systemic inflammation and organ dysfunction. PMID- 11194803 TI - Multimodal versus progressive treatment techniques to correct burn scar contractures. AB - The treatment of burn scar contractures is a major emphasis in the rehabilitation of patients with burn injuries. Many treatment techniques have been used successfully but without a critical investigation of the best practice of care. In this study, we compared the outcomes for pediatric and adult patients treated with a multimodal therapy approach to treatment techniques that are considered to be progressive to determine if differences existed in the techniques. The medical records of 52 patients with documented burn scar contractures were reviewed for patient and rehabilitation treatment parameters. Included were population demographic information and type of treatment intervention used to correct the scar contracture. In particular, the postburn day when the contracture appeared, the percentage of range of motion deficit, the day when definitive treatment that eventually corrected the contracture was begun, and the days required to correct the contracture were noted. With equal range-of-motion deficits identified, the burn scar contractures of patients in the progressive treatment group were corrected in less than half the time of the burn scar contractures of the patients in the multimodal treatment group. This result occurred despite scar contractures that appeared significantly earlier and later initiation of definitive treatment. PMID- 11194804 TI - Sprayed keratinocyte suspensions accelerate epidermal coverage in a porcine microwound model. AB - Keratinocyte suspensions can potentially treat a variety of epidermal defects, but the mechanism of action has not been fully determined. We developed a porcine model to study the effect of sprayed cell suspensions delivered on small wounds within a meshed autograft. Paired full-thickness surgically excised wounds were covered with a fully expanded 3:1 meshed split-thickness autograft. A keratinocyte cell suspension was sprayed onto half of the wounds at a seeding density of 2.8 x 10(3) cells/cm2; the remaining wounds were sprayed with cell culture medium alone. Histologic analysis at days 5 and 8 showed an increase in average epidermal thickness, confluence, keratin cysts, and blood vessels in the keratinocyte cell suspension group compared with the cell culture medium control group. Wounds sprayed with the cell suspension showed faster and better quality of epithelialization than wounds sprayed with cell culture medium alone. PMID- 11194805 TI - The efficacy and safety of fentanyl for the management of severe procedural pain in patients with burn injuries. AB - Fentanyl has been shown to be effective for the management of intense pain of short duration. We have recently used intravenous fentanyl for burn wound procedures because of its rapid onset, high potency, and short duration. In this report, we reviewed our experience with fentanyl in a variety of procedural burn pain settings to develop specific recommendations about its effectiveness and safety for the treatment of pain in patients with burn injuries. The medical records of patients with burn injuries who received fentanyl for wound procedures over a 2-year period were retrospectively reviewed. Patient demographics, the amount of fentanyl administered, the level of analgesia achieved, and the incidence of adverse effects were analyzed. Fifty-five patients who were 9 months to 75 years old with burn wounds (range, 1%-90% of total body surface area) received 148 doses of fentanyl for the treatment of procedural pain. An average of 8.0 +/- 7.0 microg/kg of fentanyl (range, 0.7 to 38.0 microg/kg) was required for the first wound procedure with fentanyl. No correlation between dosage of fentanyl given and either age or percentage of total body surface area burned was observed. Transient respiratory depression was observed in 17 patients (31%). No patient required intubation or additional supplemental oxygen after the conclusion of the procedure. High doses of fentanyl are required to achieve adequate analgesia during some burn wound procedures. Respiratory depression associated with fentanyl use is transient but requires adequate preparation and trained personnel. Fentanyl may be effectively integrated into the pain control strategy for patients with burn injuries. PMID- 11194806 TI - A survey of gram-negative bacteria survival on hospital fabrics and plastics. AB - One critical factor for the transmission of microorganisms from person to person or from the environment to a person (patient or health care worker) is the ability of the microbe to survive on an environmental surface. The purpose of this study was to determine the length of survival of various gram-negative bacteria on fabrics and plastics commonly used in hospitals. Seven materials were tested: smooth cotton (clothing), cotton terry (towels), 60% cotton-40% polyester blend (scrub suits and lab coats), polyester (drapes), 75% nylon-25% spandex (pressure garments), polyvinyl (splash aprons), and polyurethane (keyboard covers). The following bacteria were tested: Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Proteus mirabilis, Acinetobacter species, and Enterobacter species. Swatches of the materials were inoculated with defined amounts of bacteria and assayed at regular intervals. Survival was dependent on the bacterium, its inoculum size, and the material tested. At 102 microorganisms per swatch, bacteria survived from less than 1 hour to 8 days. At 10(4) to 10(5) bacteria per swatch, survival ranged from 2 hours to more than 60 days. These findings emphasize the need for careful disinfection and conscientious contact control procedures in areas that serve immunosuppressed individuals, such as patients with burn injuries. PMID- 11194807 TI - Burn injuries in rats upregulate the gene expression of the ubiquitin-conjugating enzyme E2(14k) in skeletal muscle. AB - Burn injuries are associated with muscle cachexia, which mainly reflects protein breakdown in the ubiquitin-proteasome pathway. Ubiquitination of proteins degraded by this mechanism is regulated by multiple enzymes, including the 14-kd ubiquitin-conjugating enzyme, E2(14k). In this study, burn injuries in rats resulted in increased levels of the 1.2 kilobase E2(14k) transcript in the white, fast-twitch extensor digitorum longus muscle with no changes or only minor changes in the red, slow-twitch soleus muscle, liver, and kidney. The results provide the first evidence that burn injuries upregulate the gene expression of E2(14k) in skeletal muscle and suggest that ubiquitin-proteasome-dependent muscle protein breakdown after thermal injuries may, at least in part, be regulated by E2(14k). PMID- 11194808 TI - Cost-effective use of helicopters for the transportation of patients with burn injuries. AB - We performed a retrospective review to analyze the use of helicopters for the transportation of patients with burn injuries to determine whether a more cost effective approach could be developed without impairing the quality or delivery of health care. Charts were reviewed for all patients with burn injuries who were transported by helicopter to our hospitals during a 2-year period. Patients with inhalation injuries, with burn injuries received more than 24 hours before admission or more than 200 miles from our burn center, with more than 30% total body surface area (TBSA) burned, or with associated trauma injuries were excluded. Control patients with burn injuries who were transported by ambulance were identified and matched to the patients with burn injuries transported by helicopter for the percentage of TBSA burned, the percentage of third-degree burns, transport mileage, and age. The outcome was evaluated by comparison of length of stay, days on ventilator, and mortality rate. Comparisons were performed with Student t test. The transportation charge was determined for the patients transported by helicopter who we believed were eligible for transport by ambulance. Forty-seven of 85 patients transported by helicopter matched the inclusion criteria and had survived. There was no statistically significant difference between the percentage of TBSA burned, the percentage of third-degree burns, length of stay, days on ventilator, age, or transport mileage. There was, however, a significant difference in the time from the injury to admission to the hospital, as well as in the charge for transportation. Patients who had less than 30% TBSA thermal cutaneous injuries without evidence of inhalation injury, and who are less than 200 miles from a burn center may be safely transported by ambulance. Ambulance transportation may take additional time; however, stricter protocols for helicopter transportation of patients with burn injuries will result in potentially substantial savings without affecting outcomes for patients. PMID- 11194809 TI - Analysis of hypertrophic and normal scar gene expression with cDNA microarrays. AB - Hypertrophic scar is one form of abnormal wound healing. Previous studies have suggested that hypertrophic scar formation results from altered gene expression of extracellular matrix molecules. A broadscale evaluation of gene expression in hypertrophic scars has not been reported. To better understand abnormalities in hypertrophic scar gene expression, we compared messenger RNA expression in hypertrophic scars, normal scars, and uninjured skin with the use of complementary (c)DNA microarrays. Total RNA was extracted from freshly excised human hypertrophic scars, normal scars, or uninjured skin and reverse transcribed into cDNA with the incorporation of [33P] deoxycytidine triphosphate. The resulting radioactive cDNA probes were hybridized onto cDNA microarrays of 4000 genes. Hybridization signals were normalized and analyzed. In the comparison of tissue samples, mean intensities were calculated for each gene within each group (hypertrophic scars, normal scars, and uninjured skin). Ratios of the mean intensities of hypertrophic scars to normal scars, hypertrophic scars to uninjured skin, and normal scars to uninjured skin were generated. A ratio that was greater than 1 indicated upregulation of any particular gene and a ratio that was less than 1 indicated downregulation of any particular gene. Our data indicated that 142 genes were overexpressed and 50 genes were underexpressed in normal scars compared with uninjured skin, 107 genes were overexpressed and 71 were underexpressed in hypertrophic scars compared with uninjured skin, and 44 genes were overexpressed and 124 were underexpressed in hypertrophic scars compared with normal scars. Our analysis of collagen, growth factor, and metalloproteinase gene expression confirmed that our molecular data were consistent with published biochemical and clinical observations of normal scars and hypertrophic scars. cDNA microarray analysis provides a powerful tool for the investigation of differential gene expression in hypertrophic scar samples and either uninjured skin or normal scars. Our data validate the use of this technology for future studies on gene expression during repair processes of normal and abnormal wounds. PMID- 11194810 TI - The use of inhaled nitric oxide as adjuvant therapy in patients with burn injuries and respiratory failure. AB - Inhaled nitric oxide (NO) is a relatively new modality in the management of acute respiratory distress syndrome. The purpose of this study was to examine our experience with inhaled NO in 10 adult patients with burn injuries and acute respiratory distress syndrome-related oxygenation failure. The patients had a mean age of 50 +/- 19 years and a mean burn size of 41% +/- 20% of the total body surface area. Seven patients died and 3 survived. The survivors and nonsurvivors did not differ with respect to age, burn size, pre-NO ventilator settings, or indices of oxygenation including PaO2, oxygen saturation in arterial blood, PaO2/fraction of inspired oxygen (FIO2) ratio, and alveolar-arterial oxygen tension difference. The concentration of NO administered ranged between 5 ppm and 30 ppm. PaO2, oxygen saturation in arterial blood, and the PaO2/FIO2 ratio increased in all patients. Although it was not statistically significant, survivors tended to have a more vigorous and sustained response than non survivors; this was best exemplified by the change in PFR. During the first hour of therapy, the PaO2/FIO2 ratio increased from 64.3 +/- 12.7 to 231.8 +/- 154.5 in survivors and from 93.9 +/- 44.0 to 161.5 +/- 81.8 in the nonsurvivors. After 12 hours of therapy, the PaO2/FIO2 ratio was 306.2 +/- 333.7 in the survivors and 178.9 +/- 69.9 in the nonsurvivors. There were no complications associated with the use of inhaled NO. Although a stronger early response to NO seems to occur in survivors, we cannot definitely conclude that the early response pattern is predictive of recovery. Nonetheless, we believe that inhaled NO has a useful role in the treatment of patients with burn injuries and severe acute respiratory distress syndrome-related oxygenation failure. PMID- 11194811 TI - Palm computer demonstrates a fast and accurate means of burn data collection. AB - Manual biomedical data collection and entry of the data into a personal computer is time-consuming and can be prone to errors. The purpose of this study was to compare data entry into a hand-held computer versus hand written data followed by entry of the data into a personal computer. A Palm (3Com Palm IIIx, Santa, Clara, Calif) computer with a custom menu-driven program was used for the entry and retrieval of burn-related variables. These variables were also used to create an identical sheet that was filled in by hand. Identical data were retrieved twice from 110 charts 48 hours apart and then used to create an Excel (Microsoft, Redmond, Wash) spreadsheet. One time data were recorded by the Palm entry method, and the other time the data were handwritten. The method of retrieval was alternated between the Palm system and handwritten system every 10 charts. The total time required to log data and to generate an Excel spreadsheet was recorded and used as a study endpoint. The total time for the Palm method of data collection and downloading to a personal computer was 23% faster than hand recording with the personal computer entry method (P < 0.05), and 58% fewer errors were generated with the Palm method.) The Palm is a faster and more accurate means of data collection than a handwritten technique. PMID- 11194813 TI - How should endotension be defined? History of a concept and evolution of a new term. PMID- 11194812 TI - Burn injury in kitchen workers: a cause for prevention. AB - Preventable thermal injuries in professional kitchen workers have been identified, and we have introduced a protective garment. Because of the nature of their occupation, kitchen workers are prone to thermal injuries. It has been our experience that the majority of these injuries are scald injuries on the ankles and dorsum of the feet. We propose that a protective garment, such as a waterproof shoe and garter, could reduce the incidence of these injuries. PMID- 11194814 TI - Does successful embolization of endoleaks lead to aneurysm sac shrinkage? AB - PURPOSE: To determine whether embolization of endoleaks after endovascular repair of aortic aneurysms is associated with a decrease in the diameter of the aneurysm. METHODS: Fifteen patients (13 men; median age 76 years) demonstrated primary endoleaks persisting > or =3 months after endovascular abdominal aortic aneurysm repair with a variety of commercial endografts. In 8 patients, coil embolization failed to completely obliterate the leak, whereas embolotherapy proved successful in the remaining 7 patients. Surveillance of endoleaks and the effect of their embolization on aneurysm size were followed with serial computed tomographic (CT) scans. Follow-up after embolization extended for at least 12 months. RESULTS: Patients with persistent leak exhibited a slight increase in mean aneurysm area from 21.41+/-4.25 to 22.47+/-6.70 cm2. Medians differed from 20.03 (range 16.59-28.73) to 23.03 (range 14.14-33.69) cm2 (p = 0.0078, 95% confidence interval [CI] = 0.0075 to 0.0081). Successfully treated patients, however, showed a mean decrease from 20.58+/-3.63 (median 19.87) to 16.36+/-6.46 cm2 (median 18.10) at 1 year (p = 0.0156, 95% CI = 0.0151 to 0.0160). The medians differed significantly between groups (p < 0.05). CONCLUSIONS: Persistent endoleaks after endovascular aortic aneurysm treatment led to an increase in the diameter of the aneurysm, whereas complete occlusion was associated with a significant decrease in aneurysm diameter. PMID- 11194815 TI - Aneurysm expansion and retroperitoneal hematoma after thrombolysis for stent graft limb occlusion caused by distal endograft migration. AB - PURPOSE: To describe a complication of thrombolytic therapy used to treat graft limb occlusion precipitated by distal migration and kinking of an abdominal aortic stent-graft. CASE REPORT: A 5.5-cm abdominal aortic aneurysm (AAA) in a 66 year-old woman was treated with Vanguard bifurcated stent-graft. At the 1-year follow-up, she complained of left leg claudication. Computed tomography (CT) showed a 36% reduction in maximum AAA diameter, but the stent-graft had migrated distally approximately 5 mm, and the left graft limb was occluded. Thrombolysis was initiated, but after approximately 8 hours, abdominal pain began. Emergent CT scanning revealed rapid aneurysm expansion and a retroperitoneal hematoma. Thrombolytic treatment was stopped; transfusions and thrombogenic drugs were given to restore hemodynamic stability. The aneurysm began to decrease in size. The occluded graft limb had been reopened by the lytic therapy, uncovering a stenosis in the native artery distal to the graft limb. Stent placement restored outflow. The retroperitoneal hematoma resolved over time, and the aneurysm sac shrank to its prelytic diameter. The patient is well with a functioning endograft 18 months after the occlusion (30 months after stent-grafting). CONCLUSIONS: Caution must be taken when using thrombolysis in patients with endovascular aortic grafts because unexpected bleeding complications might arise. Thrombectomy, femorofemoral bypass, or stent or stent-graft extensions might be safer alternatives for treating occluded stent-graft limbs. PMID- 11194816 TI - Role of duplex imaging in endovenous obliteration for primary venous insufficiency. AB - PURPOSE: To assess the role of duplex imaging in defining suitable pathological anatomy for endovenous obliteration and characterizing its treatment outcomes over time. METHODS: Eighteen lower limbs in 17 patients (12 women; mean age 48 years; range 29-74 years) presenting with varicose greater saphenous veins (GSVs) were treated with endovenous obliteration without adjunctive high ligation. Duplex imaging was used as an intraprocedural guidance tool for vein access and catheter positioning and for preprocedural evaluation and serial surveillance after the procedures. RESULTS: In the 18 limbs, preprocedural duplex scanning defined reflux owing to incompetence of the terminal valve (n = 6), subterminal valve (n = 9), or truncal valve (n = 3). Duplex imaging facilitated percutaneous vein puncture and was essential in catheter positioning at the saphenofemoral junction (SFJ). At 1 week, the saphenous trunks of all 18 limbs were either shrunken and obliterated (n = 7) or occluded by thrombus without shrinkage (n = 11). By 6 months, 7 GSVs were no longer sonographically visible, 10 were shrunken and obliterated, and 1 had a segmental partial recanalization. In the 15 limbs with terminal or subterminal valve incompetence at 1 week, 5 had total SFJ obliteration, 4 had > or =1 patent tributaries draining directly into the femoral vein through an open SFJ, and 6 had > or =1 patent tributaries draining into an open SFJ through a short (<2 cm) proximal saphenous trunk. By 6 months, only 1 limb had total SFJ occlusion; the other 14 had at least 1 persistent or reopened tributary. CONCLUSIONS: Duplex scanning is indispensable for selecting patients, guiding the procedure, and defining the morphological maturation and hemodynamic changes that appear to characterize successful endovenous obliteration. PMID- 11194817 TI - A retrospective comparative study of open and endoscopic saphenous vein harvesting. AB - PURPOSE: To compare the operative variables, complications, and potential benefits of endoscopic saphenous vein harvesting (ESVH) with traditional open vein retrieval for coronary artery bypass grafting (CABG). METHODS: Data were collected retrospectively on 212 consecutive CABG patients from whom saphenous veins were harvested by one surgeon using either an open saphenous vein harvesting (OSVH) technique (n = 135) or ESVH (n = 77) performed with the ENDO SAPH Vein Harvest System. Fifty-three patients underwent a purely endoscopic procedure, whereas 24 patients had either a combined endo-open procedure (n = 13) or were converted to an open technique (n = 11) because of equipment failure or adverse anatomical characteristics. Harvest time was measured from initial leg incision to aortic cross-clamping. Leg wound complications were evaluated on the basis of progressive severity. RESULTS: Harvest and procedural times were longer for the ESVH group (111 and 313 minutes, respectively) than for the OSVH patients (63 and 252 minutes, respectively, p < 0.001). Mean length of stay was not appreciably different: 11.7+/-6.2 days (range 3-52) for the OSVH group, compared with 11.0+/-6.0 days (range 3-41) for the ESVH patients (p = 0.40). Fewer complications occurred in the ESVH group when a purely endoscopic procedure was performed (17% versus 35% for OSVH, p = 0.012). Infection occurred in 1 OSVH and in 4 ESVH patients, but 3 of the endoscopic patients had a combined procedure. Bivariate correlational analysis showed that an increased number of incisions (r = 0.29, p < 0.01), obesity (r = 0.18, p < 0.01), and short stature (r = -0.16, p < 0.05) were associated with leg wound complications, but hierarchial stepwise regression analysis determined only short stature to be a predictive variable (beta = 0.17, R2 = 0.03). CONCLUSIONS: Despite increased operating time, ESVH results in fewer complications when a purely endoscopic procedure is performed. PMID- 11194818 TI - Does prosthetic covering of nitinol stents alter healing characteristics or hemodynamics? AB - PURPOSE: To evaluate placement of polyester (Dacron) coverings on nitinol stents implanted in the canine aorta to determine the effect on cross-sectional lumen area, development of intimal hyperplasia, device endothelialization, and flow hemodynamics. METHODS: Ten polyester-covered and 10 uncovered nitinol stents (60 mm length, 10- or 12-mm diameter) were deployed percutaneously in the normal infrarenal aorta of 20 adult mongrel dogs using random assignment. Angiography, intravascular ultrasound (IVUS), and duplex ultrasound performed at device deployment and before explantation at 6 weeks were used to measure aorta/device diameter and cross-sectional area. Pressure-perfusion-fixed aortic segments were compared for surface endothelialization (CD31 staining) and for thickness of neointimal formation. RESULTS: All 20 endoluminal devices were accurately positioned in the infrarenal aorta without early or delayed evidence of device thrombosis, significant lumen narrowing, or device deformity. IVUS and duplex scanning identified no anatomical stenosis in either the covered or the bare devices by duplex ultrasound; peak systolic velocity measurements were similar (106+/-25 cm/s in the covered stent versus 96+/-25 cm/s for bare stents, p > 0.05). Mean neointimal thickness was significantly greater (p < 0.005) in the covered (326+/-145 microm) compared with the bare (219+/-62 microm) stents. Intima-to-media height ratios were greater in the covered stents (3.0+/-1.1 compared with 1.1+/-0.2, p < 0.003). Mean surface area endothelialization in the proximal, middle, and distal sections of each device was similar (p > 0.05) in covered (59%, 56%, and 69%) and bare (59%, 65%, and 53%) stents. CONCLUSIONS: Deployment and balloon dilation of a covered nitinol stent in a nondiseased canine aorta increased neointimal development compared with an uncovered stent, but overall lumen cross-sectional area was preserved. No differences in device patency, intradevice thrombus formation, flow hemodynamics, or luminal endothelialization were demonstrated, despite a thicker intradevice neointima induced by the polyester covering. PMID- 11194819 TI - Differing morphological changes following endovascular AAA repair using balloon expandable or self-expanding endografts. AB - PURPOSE: To determine whether changes in aneurysm morphology after endovascular abdominal aortic aneurysm (AAA) repair differ according to the type of endograft (self-expanding versus balloon-expandable). METHODS: Among 88 patients with AAA treated with either homemade polytetrafluoroethylene (PTFE) aortomonoiliac endografts or Talent stent-grafts, 30 patients (24 males; mean age 73 years, range 55-93) were selected for this study based on a >2-year follow-up and freedom from endoleak or conversion. Of these, 12 had PTFE endografts and 18 Talent devices. All patients had spiral computed tomographic angiography with 3 dimensional reconstruction at 5 days posttreatment and 6-month intervals thereafter. Neck dimensions (length and diameters at 3 levels) were measured, along with volumes and maximal diameters of the sac and lengths of the aneurysm and endograft. Intra- and interobserver errors were <5% for linear and volume measurements. RESULTS: Both groups had an initial 20-mL increase in median volume (p = 0.02) followed, only in Talent patients, by marked shrinkage at 6 months ( 87.4 mL; p = 0.09). PTFE patients had no further changes in sac volume. Maximal sac diameters reflected volumes, but only after day 5. PTFE patients had an immediate increase (p = 0.03) in aneurysm neck diameters, which then remained stable. Talent patients had continuing increases in diameter to 6 months (p < 0.05), with no change thereafter. Length changes were not significant in either group. PTFE patients had an increase in median aneurysm length at day 5 (+3.2 mm, p = 0.04) and again at 1.5 years (+6.4 mm, p = 0.03). Endograft length slowly increased (+18.7 mm) over 1.5 years (p = 0.02). Talent patients had no length changes in the device or aneurysm. CONCLUSIONS: Aneurysm morphology appeared to alter according to the type of endograft deployed. With PTFE endografts, aneurysm volume does not change, whereas impressive sac shrinkage occurs in conjunction with the Talent system. Aneurysm/graft lengths increase with unsupported stent grafts. Neck diameter increases immediately with balloon-expandable endografts and then remains constant. In the self-expanding models, neck diameter increases at 6 months but not thereafter. PMID- 11194820 TI - An endovascular model of carotid stenosis for the evaluation of thrombolysis and angioplasty. AB - PURPOSE: To develop a porcine carotid artery thrombosis model using a novel stent graft device to evaluate the efficacy of thrombolytic therapy and angioplasty procedures. METHODS: An endovascular device made from a tapered polytetrafluoroethylene graft inverted in a self-expanding nitinol stent was delivered to bilateral carotid arteries via a right femoral approach in 16 pigs. Carotid thrombotic occlusion ensued from flow stasis created by the intrastent stenosis. Via selective carotid catheterization from a femoral approach, urokinase (250,000 IU) was pulse-sprayed in one carotid artery while a control saline solution was infused in the contralateral vessel; delivery times were 1 hour, 8 hours, 3 days, or 6 days after carotid occlusion (4 animals per time period). After thrombolysis, balloon angioplasty was performed to maintain carotid patency. Arteriography and intravascular ultrasound were used to evaluate the efficacy of thrombolysis. Light microscopy was used for histological analysis of the thrombus. RESULTS: Carotid artery occlusion occurred in 15+/-8 minutes after stent-graft placement in all animals. Urokinase was effective in recanalizing all occluded arteries in the 1-hour, 4-hour, and 3-day groups (100%) but was effective in only 2 of 4 animals in the 6-day group (p < 0.05). Overall thrombolytic efficacy was 78%+/-7%. Control saline solution showed no thrombolytic effect (p < 0.001). Angioplasty successfully restored normal luminal diameter in all fully lysed arteries (100%). Histological analysis showed fibrin predominant thrombus with a varying degree of platelet deposition. CONCLUSIONS: This endovascular approach, which creates a carotid stenosis using this novel stent-graft device, is reliable in producing carotid thrombosis. In our model, thrombolytic therapy was effective in restoring luminal patency, and the intraluminal stenosis is amenable to balloon angioplasty. The model is useful for the evaluation of antithrombotic therapy and adjunctive endovascular interventions. PMID- 11194821 TI - Does complete aneurysm exclusion ensure long-term success after endovascular repair? AB - PURPOSE: To examine whether complete aneurysm exclusion is a reliable marker for successful long-term endovascular abdominal aortic aneurysm (AAA) repair. METHODS: The medical records, computed tomographic (CT) scans, and duplex examinations of all the patients who underwent endovascular AAA repair at a single institution and had at least 12 months of follow-up were reviewed. Sixty seven patients (58 men; mean age 74 years, range 57-87) were identified. Complete aneurysm exclusion was defined by the absence of an endoleak at any time before an adverse event. The primary endpoint included all major adverse events that occurred during the postoperative period, including aneurysm expansion, acute symptoms referable to the AAA, late secondary procedures, ruptures, and deaths from ruptures and all other causes. RESULTS: There were 44 adverse events (8 expanding aneurysms, 4 acute symptoms, 17 secondary procedures, and 15 deaths from other causes) in 28 (42%) patients. Among 36 (54%) patients who had initial complete aneurysm exclusion (no endoleak), 12 (33%) experienced adverse events, compared with 16 (52%) events in 31 patients who had endoleak (chi2 = 1.59, p = 0.21). CONCLUSIONS: There was no statistically significant difference in adverse events based on the presence or absence of endoleak. Complete aneurysm exclusion as defined by absence of an endoleak does not indicate an event-free postoperative course. A better marker of clinical success of endovascular AAA repair is needed. PMID- 11194822 TI - Percutaneous stenting of an latrogenic superior mesenteric artery dissection complicating suprarenal aortic aneurysm repair. AB - PURPOSE: To report endovascular repair of an iatrogenic superior mesenteric artery (SMA) dissection caused by a balloon occlusion catheter. CASE REPORT: A 68 year-old man with a suprarenal aortic aneurysm underwent conventional prosthetic replacement, during which visceral artery back bleeding was controlled with balloon occlusion catheters. Six hours postoperatively, the patient experienced an episode of bloody diarrhea with abdominal pain and tenderness and mild metabolic acidosis. Colonoscopy revealed colitis (grade I) without necrosis of the right and left colon. An emergent abdominal computed tomographic scan showed signs of mesenteric ischemia with bowel dilatation and SMA wall hematoma; angiography identified a dissection 1 cm distal to the SMA origin. An Easy Wallstent was deployed percutaneously, successfully reestablishing SMA patency. The postoperative course was uneventful, and the patient remains asymptomatic with a patent SMA stent and aortic graft at 1 year. CONCLUSIONS: latrogenic SMA dissection should be suspected after suprarenal aortic aneurysm repair if signs of mesenteric ischemia arise. Prompt and thorough imaging studies are necessary to confirm the diagnosis and assess the potential for an endoluminal treatment. PMID- 11194823 TI - Transseptal guidewire stabilization facilitates stent-graft deployment for persistent proximal ascending aortic dissection. AB - PURPOSE: To report endovascular repair of a DeBakey type I ascending aortic dissection. CASE REPORT: Five months after aortocoronary bypass grafting, a 56 year-old woman demonstrated a persistent ascending aortic type I dissection whose entry tear proximal to the innominate artery spiraled down the descending thoracic aorta into the iliofemoral arteries. Repair was facilitated with a guidewire passed through a transseptal sheath in the right femoral vein. The guidewire traversed the right and left atria and the left ventricle and then exited into the ascending aorta and was exteriorized through the right femoral artery. A right brachial catheter aided contrast visualization of the innominate artery. Adenosine-induced elective cardiac arrest promoted precise placement of a customized polyester-covered balloon-expandable stent, which closed the aortic rent. CONCLUSIONS: A transseptal approach enables the guidewire to follow the curvature of the aortic arch, providing precise control of the stent-graft delivery system. This case illustrates the applicability of endovascular techniques to repair ascending aortic pathologies using readily available techniques, equipment, and drugs. PMID- 11194824 TI - Hybrid open-endoluminal technique for repair of thoracoabdominal aneurysm involving the celiac axis. AB - PURPOSE: To describe a technique combining endoluminal and open approaches for the repair of thoracoabdominal aneurysms involving the celiac axis. CASE REPORT: Two patients with type I thoracoabdominal aneurysm and suboptimal cardiac reserve underwent transluminal stent-graft implantation. To achieve satisfactory distal seal, the caudal end of the endograft was circumscribed with a Dacron band that was sutured to the aorta and endograft through a midline incision. The patent celiac artery in both patients was ligated to stop retrograde filling of the aneurysm sac. The patients developed no problems perioperatively, and exclusion of the aneurysms was confirmed by follow-up imaging. Three years after endografting, both patients had excluded aneurysms without evidence of endoleak or device migration. CONCLUSIONS: This combined approach is another treatment option for thoracic aneurysms that have an anatomically suitable proximal attachment zone with a compromised distal neck. PMID- 11194826 TI - Endograft surveillance: a priority for long-term device performance. PMID- 11194825 TI - Endoleaks and the need for a paradigm shift. PMID- 11194827 TI - A reply. PMID- 11194828 TI - Modulation of Th1/Th2 subsets by granulocyte-colony stimulating factor. PMID- 11194829 TI - Th1/Th2 lymphokine profile of T cells present in the blood of granulocyte-colony stimulating factor-treated stem-cell donors: up or down modulation. PMID- 11194830 TI - Clinical trial claims instructions issued. PMID- 11194831 TI - Customized patient bills can improve customer service. PMID- 11194832 TI - Health care access and use among low-income children: who fares best? AB - In this paper we assess how access to care and use of services among low-income children vary by insurance status. Although 40 percent of low-income children rely on private health insurance, little is known about how this coverage compares with Medicaid coverage in meeting their health care needs. We find that Medicaid and privately insured low-income children appear to have fairly comparable access but that Medicaid-covered children are more likely to receive services and to have more visits when they receive care. Expanding public coverage may not be sufficient to ensure that all low-income children have access to comprehensive and high-quality care. It may require improvements in preventive and dental care for children with private coverage, an area in which states have limited influence. PMID- 11194833 TI - Back to school: a health care strategy for youth. AB - School-based health centers (SBHCs) are a policy innovation designed to increase health care access among youth. The centers offer primary and acute care, often to underserved populations. We describe SBHCs, trace their history, and analyze the three great political challenges they face: moral opposition triggered by concern about reproductive health services in schools; funding in a managed care era; and partisan state politics. We show how the centers have been meeting these challenges. Finally, we consider the prospect of this innovation going to scale across the nation. PMID- 11194834 TI - A founder of quality assessment encounters a troubled system firsthand. Interview by Fitzhugh Mullan. PMID- 11194835 TI - HealthMarts, HIPCs (health insurance purchasing cooperatives), MEWAs (multiple employee welfare arrangements), and AHPs (association health plans): a guide for the perplexed. AB - This paper considers how pending proposals to authorize new forms of group purchasing arrangements for health insurance would fit and function within the existing, highly complex market and regulatory landscape and whether these proposals are likely to meet their stated objectives and avoid unintended consequences. Cost savings are more likely to result from increased risk segmentation than through true market efficiencies. Thus, these proposals could erode previous market reforms whose goal is increased risk pooling. On the other hand, these proposals contain important enhancements, clarifications, and simplification of state and federal regulatory oversight of group purchasing vehicles. Also, they address some of the problems that have hampered the performance of purchasing cooperatives. On balance, although these proposals should receive cautious and careful consideration, they are not likely to produce a significant overall reduction in premiums or increase in coverage. PMID- 11194836 TI - Have small-group health insurance purchasing alliances increased coverage? AB - We use data from 1993 and 1997 employer surveys to assess whether the three largest statewide small-group health insurance purchasing alliances--in California, Connecticut, and Florida--increased coverage in small business. They did not. Specifically, they did not reduce small-group market health insurance premiums, and they did not raise small-business health insurance offer rates. We explore and discuss some reasons why. Alliances do permit employers to offer much greater choice in the number and types of plans; employees are found to take advantage of this wider choice. PMID- 11194837 TI - Consumer-choice purchasing pools: past tense, future perfect? PMID- 11194838 TI - Shifting health insurance coverage, 1997-1999. PMID- 11194839 TI - How a changing workforce affects employer-sponsored health insurance. PMID- 11194840 TI - Generation vexed: age-cohort differences in employer-sponsored health insurance coverage. PMID- 11194841 TI - Communicating health information through the entertainment media. PMID- 11194842 TI - Prospects for improved decision making about medical necessity. PMID- 11194843 TI - Using and misusing anecdote in policy making. PMID- 11194844 TI - Out of the closet and into the legislature: breast cancer stories. PMID- 11194845 TI - Betwixt and between: targeting coverage reforms to those approaching Medicare. AB - Recent Medicare buy-in proposals agree on setting eligibility at age sixty-two but disagree on linking eligibility to loss of employer insurance or ability to pay. We examine arguments for targeting incremental coverage for older Americans in these ways. While access to retiree health insurance is declining, we question whether targeting loss of employer insurance can address many older Americans' insurance problems. Furthermore, focusing on persons ages sixty-two to sixty-four misses a large group of persons in poor health with limited resources. Efforts to improve coverage for older Americans should consider trade-offs between defining eligibility by age versus ability to pay. PMID- 11194846 TI - Covering the uninsured through TennCare: does it make a difference? AB - Tennessee created TennCare in 1994 to address the needs of "poor and uninsured citizens ... excluded from the health care system." Under TennCare, Tennessee implemented managed care in its Medicaid program and used savings anticipated from the switch to expand insurance coverage to uninsured and uninsurable adults and children. Our analysis of the expansion suggests that it improved access to care, reduced unmet need, and encouraged use of preventive services, particularly for children. These changes coincided with higher levels of satisfaction with care among TennCare beneficiaries. PMID- 11194847 TI - Patterns of insurance coverage within families with children. AB - This paper examines patterns of health insurance within families with children, using the 1996 Medical Expenditure Panel Survey (MEPS). Four and a half million families (14 percent) had insurance for some, but not all, family members. These partially insured families generally obtained coverage because of one of three situations: (1) A parent earned relatively higher wages and received the concomitant benefits of such jobs but could not afford dependent coverage; (2) the family had young children who were covered by Medicaid through more generous eligibility thresholds for children under age six, while other family members were ineligible; or (3) the family had a member who was eligible for public coverage because of a disability. Each of these situations offers the platform from which incremental policies might efficiently expand coverage to families. PMID- 11194848 TI - Left out: immigrants' access to health care and insurance. AB - Recent policy changes have limited immigrants' access to insurance and to health care. Fewer noncitizen immigrants and their children (even U.S.-born) have Medicaid or job-based insurance, and many more are uninsured than is the case with native citizens or children of citizens. Noncitizens and their children also have worse access to both regular ambulatory and emergency care, even when insured. Immigration status is an important component of racial and ethnic disparities in insurance coverage and access to care. PMID- 11194849 TI - Unfriendly shores: how immigrant children fare in the U.S. health system. AB - The proliferation of poor immigrant children in the United States raises concern about their high uninsurance rates and access to care. We examined the joint effects of health insurance status and place of birth on use of health services by children of the working poor. Of foreign-born children, 52 percent were uninsured and 66 percent had a regular care source, compared with 20 percent and 92 percent, respectively, of native-born children. Foreign-born uninsured children were less likely than their native-born peers were to have a regular care source or to have sought care. Health insurance and immigration policies must act in concert to increase health care access for foreign-born children. PMID- 11194850 TI - Assessing the impact of health plan choice. AB - Many health policy researchers have argued that increased insurance plan choice will enhance the efficiency of the health care system. However, relatively little is known about plan choice and its association with insurance coverage and access to and satisfaction with health care. Using data from the 1996 Medical Expenditure Panel Survey, we find that 55 percent of workers had plan choice in that year. Approximately 26 percent of workers with choice obtained it through a family member. Controlling for other factors, plan choice is associated with higher levels of employment-based insurance coverage and a greater likelihood that workers are satisfied that their families' health care needs are being met. PMID- 11194852 TI - Use of antihypertensive drugs by Medicare enrollees: does type of drug coverage matter? AB - Research has demonstrated that Medicare beneficiaries with drug coverage consume more clinically essential drugs. However, generosity of coverage varies considerably across beneficiaries. This study examines the association between types of drug coverage and the consumption and cost per tablet of essential antihypertensive medications among beneficiaries with hypertension. The findings indicate that while both state- and employer-sponsored drug coverage are associated with greater consumption of antihypertensive drugs and lower out-of pocket costs per tablet, private supplemental coverage is not associated with greater use and is associated with only slightly lower out-of-pocket costs than among noncovered beneficiaries. PMID- 11194851 TI - Covering the low-income uninsured: the case for expanding public programs. PMID- 11194853 TI - Working with employers to increase SCHIP (State Children's Health Insurance Program) enrollment. PMID- 11194854 TI - Medicaid coverage for tobacco-dependence treatments. PMID- 11194855 TI - More on Medicare competitive pricing. PMID- 11194856 TI - Reorganizing HCFA: another look. PMID- 11194857 TI - HCFA reorganization: not a simple task. PMID- 11194858 TI - Medical professionalism: another view. PMID- 11194859 TI - Building a consensus for expanding health coverage. AB - Despite a flourishing economy and recent growth in employment-based health coverage, forty-three million Americans remain uninsured. Extending coverage to the uninsured is not an intractable public policy problem but could be addressed if the various health care stakeholders could only find common ground. We argue that to win broad-based support from across the ideological and political spectra, a meaningful proposal should achieve a balance between public- and private-sector approaches, focus attention on those who are most in need of assistance (low-income workers), and build on systems that work today. With the aim of pulling together a political coalition, we present a proposal specific enough to attract support but whose details will arise later, in the context of the legislative process. PMID- 11194860 TI - Window shopping: state health reform politics in the 1990s. AB - Throughout the 1990s states sought politically acceptable policies to reduce the ranks of the uninsured. Visions of comprehensive health reform and universal coverage yielded by mid-decade to more modest measures to repair private health insurance markets, and to these enactments were added several new public programs (state and federal) to expand coverage for lower-income children and, in some cases, adults. Because governments remain ill equipped to counter the power of business, insurers, and providers in conflicts fought on private turf, reform agendas have been more readily set, moved, and cleared in public-sector arenas. Although the number of uninsured rose steadily until 1999, "catalytic federalism" -the accelerating interplay between state and federal reform forces and funds- may be putting the programmatic foundations for broader coverage incrementally into place. PMID- 11194861 TI - Will new leadership address the issue of the uninsured? PMID- 11194862 TI - Increments toward what? AB - Incremental proposals to expand health insurance coverage, such as expansions of the State Children's Health Insurance Program (SCHIP) or creation of new tax credits, should be examined for the values that underlie them and for how they structure future options for additional incremental coverage expansions. This paper examines five design issues in incremental reform: who determines coverage options for the newly insured; what risk pool do they enter; what is the government's contribution toward their coverage; what barriers are created by efforts to encourage efficiency; and how are issues of federalism handled? Tax credits are a departure from past approaches, while an SCHIP expansion is a continuation of current policy directions. PMID- 11194863 TI - Expanding coverage: reflections on recent efforts. AB - This paper focuses on the major health care initiatives and proposals that policymakers have enacted or considered since 1980 and describes what we can learn from these efforts to expand coverage. Most proposals have focused on incremental strategies, through expansion of public programs or tax incentives for the purchase of private coverage, although universal proposals have also emerged. Incremental approaches, which seem more politically feasible, still involve complex policy trade-offs. Efforts to improve take-up rates of public and private insurance could greatly expand coverage as well. PMID- 11194864 TI - Expanding coverage via tax credits: trade-offs and outcomes. AB - In this paper we discuss various options for using refundable tax credits to reduce the number of uninsured persons. The effect of tax credits on the number of uninsured depends on the form of the credit scheme adopted. Moreover, since large subsidies for private insurance directed to low-income persons have never been implemented, there is considerable uncertainty about the effect of various tax credit proposals. We find that small credits will do little to reduce the number of uninsured but that credits covering about half of the premium for a benchmark policy might have a significant effect, especially if they take a fixed dollar form and can be used for policies with few restrictions. Finally, we discuss the normative issues surrounding the "costs" of these credits schemes, and the policy issues raised by the uncertainty of the effects. PMID- 11194865 TI - Medicaid for children: federal mandates, welfare reform, and policy backsliding. AB - The 1996 federal welfare reform law delinked Medicaid enrollment from welfare participation. This paper estimates the impact of welfare reform on children's Medicaid enrollment using a methodology that both adjusts for income and other demographic differences over time and across states, and provides income-specific estimates of enrollment. The results indicate large enrollment declines: Between 1995 and 1998, enrollment probabilities for children in families with no income declined from 81 percent to 68 percent, while at half the poverty line, the decline was from 61 percent to 53 percent. This implies that 926,000 to 1.37 million fewer children were enrolled after welfare reform. At the state level, Medicaid declines and welfare reform were strongly associated, with only a few states succeeding in preserving children's Medicaid coverage. PMID- 11194866 TI - Amplification methods for the immunolocalization of rare molecules in cells and tissues. AB - The needs to precisely assign macromolecules to specific locations and domains within tissues and cells and to reveal antigens which are present in low or even in trace amounts, led to the elaboration of a wide spectrum of immunocytochemical amplification procedures. These arise from the successive improvements of tissue preparation techniques, of antigen retrieval procedures and of immunological or non-immunological detection systems. Improvement of detection systems may be the most active in the development of amplification techniques. Since the early work of Coons, in which by the introduction of the indirect technique has started amplifying the signal, different systems have succeeded in increasing the sensitivity of antigens detection. Indeed, amplification techniques such as the multiple antibody layers, the multiple bridges, the enzyme complexes, the avidin biotin, the silver intensification, and the numerous variations and combinations among these have increased the sensitivity for the detection of scarce tissue antigens. However, as shown by the recent progress carried out with new approaches such as the catalyzed reporter deposition (CARD) and the enhanced polymer one-step staining (EPOS), more efficient methods are still needed. In electron microscopy, few techniques have reached the resolution afforded by the post-embedding immunogold approach. In spite of this and in order to further increase its sensitivity, new probes and novel approaches are allowing combination of the gold marker with the amplification capacity of enzymes afforded by the CARD technique. Immunogold amplification strategies, such as the multiple incubations with the primary antibody and the use of an anti-protein A antibody have also led to enhanced signals displaying the advantages in terms of resolution and possibilities of quantification inherent to the colloidal gold marker. PMID- 11194867 TI - Role of the nucleoid-associated protein H-NS in the synthesis of virulence factors in the phytopathogenic bacterium Erwinia chrysanthemi. AB - The ability of the enterobacterium Erwinia chrysanthemi to induce pathogenesis in plant tissue is strongly related to the massive production of plant-cell-wall degrading enzymes (pectinases, cellulases, and proteases). Additional factors, including flagellar proteins and exopolysaccharides (EPS), also are required for the efficient colonization of plants. Production of these virulence factors, particularly pectate lyases, the main virulence determinant, is tightly regulated by environmental conditions. The possible involvement of the protein H-NS in this process was investigated. The E. chrysanthemi hns gene was cloned by complementation of an Escherichia coli hns mutation. Its nucleotide sequence contains a 405-bp open reading frame that codes for a protein with 85% identity to the E. coli H-NS protein. An E. chrysanthemi hns mutant was constructed by reverse genetics. This mutant displays a reduced growth rate and motility but an increased EPS synthesis and sensitivity toward high osmolarity. Furthermore, pectate lyase production is dramatically reduced in this mutant. The hns mutation acts on at least two conditions affecting pectate lyase synthesis: induction of pectate lyase synthesis at low temperatures (25 degrees C) is no longer observed in the hns mutant and induction of pectate lyase production occurs in the late stationary growth phase in the hns background, instead of in the late exponential growth phase as it does in the parental strain. Moreover, the E. chrysanthemi hns mutant displays reduced virulence on plants. Taken together, these data suggest that H-NS plays a crucial role in the expression of the virulence genes and in the pathogenicity of E. chrysanthemi. PMID- 11194868 TI - Genetic identification of multiple biological roles associated with the capsid protein of satellite panicum mosaic virus. AB - Satellite panicum mosaic virus (SPMV), an 824-nucleotide, positive-sense, single stranded RNA virus, depends on Panicum mosaic virus (PMV) for replication and spread in host plants. Compared with PMV infection alone, symptoms are intensified and develop faster on millet plants infected with SPMV and PMV. SPMV encodes a 157 amino acid capsid protein (CP) (17.5 kDa) to encapsidate SPMV RNA and form T = 1 satellite virions. The present study identifies additional biological activities of the SPMV CP, including the induction of severe chlorosis on proso millet plants (Panicum miliaceum cv. Sunup or Red Turghai). Initial deletion mutagenesis experiments mapped the chlorosis-inducing domain to amino acids 50 to 157 on the C-terminal portion of the SPMV CP. More defined analyses revealed that amino acids 124 to 135 comprised a critical domain associated with chlorosis induction and virion formation, whereas the extreme C-terminal residues 148 to 157 were not strictly essential for either role. The results also demonstrated that the absence of SPMV CP tended to stimulate the accumulation of defective RNAs. This suggests that the SPMV CP plays a significant role in maintaining the structural integrity of the full-length satellite virus RNA and harbors multiple functions associated with pathogenesis in SPMV-infected host plants. PMID- 11194869 TI - Uncoupling resistance from cell death in the hypersensitive response of Nicotiana species to cauliflower mosaic virus infection. AB - Cauliflower mosaic virus strain W260 elicits a hypersensitive response (HR) in leaves of Nicotiana edwardsonii, an interspecific hybrid derived from a cross between N. glutinosa and N. clevelandii. Interestingly, we found that N. glutinosa is resistant to W260, but responds with local chlorotic lesions rather than necrotic lesions. In contrast, N. clevelandii responds to W260 with systemic cell death. The reactions of the progenitors of N. edwardsonii to W260 infection indicated that each contributed a factor toward the development of HR. In this study, we present two lines of evidence to show that the resistance and cell death that comprise the HR elicited by W260 can indeed be uncoupled. First, we showed that the non-necrotic resistance response of N. glutinosa could be converted to HR when these plants were crossed with N. clevelandii. Second, we found that cell death and resistance segregated independently in the F2 population of a cross between N. edwardsonii and N. clevelandii. We concluded that the resistance of N. edwardsonii to W260 infection was conditioned by a gene derived from N. glutinosa, whereas cell death was conditioned by a gene derived from N. clevelandii. An analysis of pathogenesis-related (PR) protein expression in response to W260 infection revealed that elicitation of PR proteins was associated with resistance rather than with the onset of cell death. PMID- 11194870 TI - Modulations in gene expression and mapping of genes associated with cyst nematode infection of soybean. AB - Infection of the soybean root by the soybean cyst nematode (SCN) (Heterodera glycines Ichinohe) induces a well-documented, yet poorly understood, response by the host plant. The plant response, involving the differentiation of a feeding structure, or "syncytium," facilitates the feeding and reproduction of the nematode to the detriment of the host. We used a genetic system involving a single dominant soybean gene conferring susceptibility to an inbred nematode strain, VL1, to characterize the nematode-host interaction in susceptible line PI 89008. The restriction fragment length polymorphism marker pB053, shown to map to a major SCN resistance locus, cosegregates with resistance among F2 progeny from the PI 89008 x PI 88287 cross. Cytological examination of the infection process confirmed that syncytium development in this genetic system is similar to that reported by others who used noninbred nematode lines. Our study of infected root tissue in the susceptible line PI 89008 revealed a number of genes enhanced in expression. Among these are catalase, cyclin, elongation factor 1alpha, beta-1,3 endoglucanase, hydroxy-methylglutaryl coenzyme A reductase, heat shock protein 70, late embryonic abundant protein 14, and formylglycinamidine ribonucleotide synthase, all of which we have genetically positioned on the public linkage map of soybean. Formylglycinamidine ribonucleotide synthase was found to be tightly linked with a major quantitative trait locus for SCN resistance. Our observations are consistent with the hypothesis proposed by others that feeding site development involves the dramatic modulation of gene expression relative to surrounding root cells. PMID- 11194871 TI - Early symbiotic responses induced by Sinorhizobium meliloti iIvC mutants in alfalfa. AB - A mutation in the ilvC gene of Sinorhizobium meliloti 1021 determines a symbiotically defective phenotype. ilvC mutants obtained from different S. meliloti wild-type strains are able to induce root hair deformation on alfalfa roots and show variable activation of the common nodulation genes nodABC. All of these mutants are noninfective. The presence of extra copies of nodD3-syrM in an IlvC- background does not promote nod expression but allows the detection of low levels of Nod factor production. The sulphation of the Nod factor metabolites, however, is not affected. Furthermore, IlvC- strains induce a specific pattern of starch accumulation on alfalfa roots as well as of early nodulin expression. Hence, the pleiotropic action of the ilvC gene in S. meliloti may reveal novel complexities involved in the symbiotic interaction. PMID- 11194872 TI - Legume models strut their stuff. PMID- 11194873 TI - Functional screening yields a new beta-1,4-endoglucanase gene from Heterodera glycines that may be the product of recent gene duplication. AB - Clones with secreted cellulolytic activity were identified when a cDNA library constructed from poly A(+) RNA of preparasitic second-stage juveniles of Heterodera glycines, the soybean cyst nematode, was expressed in the Escherichia coli SOLR strain and overlaid with a carboxymethylcellulose (CMC) substrate. Twenty CMC-degrading clones were analyzed, and all were either identical or strongly similar to a beta-1,4-endoglucanase gene (HG-eng-2), previously isolated from H. glycines. A subgroup of identical "HG-eng-2-like" clones had considerable differences in the 5' untranslated region compared with HG-eng-2 and were designated HG-eng-3. One H. glycines genomic clone contained HG-eng-2 and HG-eng 3 full-length genes, separated by a distance of approximately 8 kb, and a second genomic clone contained two copies of HG-eng-2, separated by approximately 6.5 kb, suggesting the presence of endoglucanase gene clusters in H. glycines. The HG eng-2 and HG-eng-3 genes were in opposite transcriptional orientation, with considerable nucleotide differences in their 5' flanking regions. The highly conserved nucleotide sequence in the introns and exons and their close proximity within the genome suggest that HG-eng-2 and HG-eng-3 are the products of recent gene duplication and inversion. PMID- 11194874 TI - Molecular cloning of a cDNA encoding an amphid-secreted putative avirulence protein from the root-knot nematode Meloidogyne incognita. AB - Amplified fragment length polymorphism fingerprinting of three pairs of Meloidogyne incognita near-isogenic lines (NILs) was used to identify markers differential between nematode genotypes avirulent or virulent against the tomato Mi resistance gene. One of these sequences, present only in the avirulent lines, was used as a probe to screen a cDNA library from second-stage juveniles (J2s) and allowed cloning of a cDNA encoding a secretory protein. The putative full length cDNA, named map-1, encoded a 458 amino acid (aa) protein containing a predictive N-terminal secretion signal peptide. The MAP-1 sequence did not show any significant similarity to proteins deposited in databases. The internal part of the protein, however, was characterized by highly conserved repetitive motives of 58 or 13 aa. Reverse transcription polymerase chain reaction (RT-PCR) experiments confirmed that map-1 expression was different between avirulent and virulent NILs. In PCR reactions, map-1-related sequences were amplified only in nematode populations belonging to the three species against which the Mi gene confers resistance: M. arenaria, M. incognita, and M. javanica. Polyclonal antibodies raised against a synthetic peptide deduced from the MAP-1 sequence strongly labeled J2 amphidial secretions in immunofluorescence microscopy assays, suggesting that MAP-1 may be involved in the early steps of recognition between (resistant) plants and (avirulent) nematodes. PMID- 11194875 TI - Inhibition of fungal appressorium formation by pepper (Capsicum annuum) esterase. AB - A pepper esterase gene (PepEST) that is highly expressed during an incompatible interaction between pepper (Capsicum annuum) and the anthracnose fungus Colletotrichum gloeosporioides has been previously cloned. Glutathione-S transferase-tagged recombinant PepEST protein expressed in Escherichia coli showed substrate specificity for p-nitrophenyl esters. Inoculation of compatible unripe pepper fruits with C. gloeosporioides spores amended with the recombinant protein did not cause anthracnose symptoms on the fruit. The recombinant protein has no fungicidal activity, but it significantly inhibits appressorium formation of the anthracnose fungus in a dose-dependent manner. An esterase from porcine liver also inhibited appressorium formation, and the recombinant protein inhibited appressorium formation in the rice blast fungus, Magnaporthe grisea. Inhibition of appressorium formation in M. grisea by the recombinant protein was reversible by treatment with cyclic AMP (cAMP) or 1,16-hexadecanediol. The results suggest that the recombinant protein regulates appressorium formation by modulating the cAMP-dependent signaling pathway in this fungus. Taken together, the PepEST esterase activity can inhibit appressorium formation of C. gloeosporioides, which may result in protection of the unripe fruit against the fungus. PMID- 11194876 TI - Oxidative burst in alfalfa-Sinorhizobium meliloti symbiotic interaction. AB - Reactive oxygen species are produced as an early event in plant defense response against avirulent pathogens. We show here that alfalfa responds to infection with Sinorhizobium meliloti by production of superoxide and hydrogen peroxide. This similarity in the early response to infection by pathogenic and symbiotic bacteria addresses the question of which mechanism rhizobia use to counteract the plant defense response. PMID- 11194877 TI - Cloning and characterization of a bean UDP-glucosyltransferase cDNA expressed during plant-bacterial interactions. AB - A cDNA clone, which corresponds to an RNA transcript that accumulates in bean during the hypersensitive reaction, was isolated and designated Hra25 (for hypersensitive reaction associated). Hra25 is predicted to encode a UDP glucosyltransferase. Northern analysis was used to study Hra25 transcript accumulation in bean in response to incompatible and compatible strains of Pseudomonas syringae, an Hrp- mutant, and wounding. Our data suggest that the Hra25 transcript is activated in response to specific avr-derived signals as well as non-avr, general signals. PMID- 11194878 TI - Azorhizobium caulinodans ORS571 colonizes the xylem of Arabidopsis thaliana. AB - Improved conditions were used for the aseptic growth of Arabidopsis thaliana to investigate whether xylem colonization of A. thaliana by Azorhizobium caulinodans ORS571 might occur. When seedlings were inoculated with ORS571 (pXLGD4) tagged with the lacZ reporter gene, nearly all of the plants showed blue regions of ORS571 colonization at lateral root cracks (LRC). The flavonoids naringenin and liquiritigenin significantly stimulated colonization of LRC by ORS571. Blue bands of ORS571 (pXLGD4) bacteria were observed histochemically in the xylem of intact roots of inoculated plants. Detailed microscopic analysis of sections of primary and lateral roots from inoculated A. thaliana confirmed xylem colonization. Xylem colonization also occurred with an ORS571 nodC mutant deficient in nodulation factors. There was no significant difference in the percentage of plants with xylem colonization or in the mean length of xylem colonized per plant between plants inoculated with either ORS571 (pXLGD4) or ORS571::nodC (pXLGD4), with or without naringenin. PMID- 11194879 TI - Construction of a derivative of Agrobacterium tumefaciens C58 that does not mutate to tetracycline resistance. AB - Agrobacterium tumefaciens C58 mutates to tetracycline resistance at high frequency, complicating the use of many broad-host-range cloning and binary vectors that code for resistance to this antibiotic as the selection marker. Such mutations are associated with a resistant gene unit, tetC58, that is present in the genome of this strain. By deleting the tetC58 locus, we constructed NTL4, a derivative of C58 that no longer mutates to tetracycline resistance. The deletion had no detectable effect on genetic or physiological traits of NTL4 or on the ability of this strain to transform plants. PMID- 11194880 TI - DNA of nonhuman primates harbors hepatitis C-virus-specific sequences of its 5' non-coding region (5'-NCR). AB - The DNA from PBMCs of both hepatitis C virus (HCV)-positive patients and healthy HCV-negative human individuals tested thus far contains essential parts--up to 272/341 nucleotides--of the HCV 5'-non-coding region (5'-NCR). These findings bring up the question of the possible evolutionary background of these sequences. Therefore, using the same methodology, we looked for the same sequences in animals closely related to man, i.e., in nonhuman primates (two chimpanzees, one orang-utan, one Debrazza monkey, two New World monkey species and a prosimian). The DNA from PBMCs of the studied animals belonging to nonhuman primates contains essential parts--up to 272/341 nucleotides--of the HCV 5'-non-coding region (5' NCR). A common sequence of 82 nucleotides is contained in the DNA of all the tested animals but only the chimpanzee's DNA harbors the same, longer sequence region of 272/341 nucleotides of the 5'-NCR found in human DNA. The results may provide a clue as to the possible origin of parts of the IRES containing sequence area of the HCV. PMID- 11194881 TI - Modified percutaneous endoscopic gastrostomy (PEG) with gastropexy--early experience with a new introducer technique. AB - OBJECTIVE: The Cliny PEG 13 has been available since 1999 for clinical use in the modified introducer technique in combination with endoscopically controlled gastropexy. Data on indication, insertion technique and safety have not yet been reported in the literature. METHODS: During the time period from January 1999 to June 2000, from a total of 457 patients receiving a PEG 27 (5.9%) subjects, in whom the insertion of a PEG by means of pull-through technique was impossible or only in combination with an intervention e.g. bougienage were included in this prospective study. Each patient received a Cliny PEG 13 by means of introducer technique with endoscopically controlled double gastropexy. Tumor patients with severe stenosis made up more than 90% of the cases. The insertion and 30 day follow-up were performed using a standardized protocol. Method-related and unrelated complications were recorded. RESULTS: PEG insertion was successful in all patients without additional intervention. We did not see any method-related complications. The peri-interventional local infection rate was 3.7%. One patient died during the 30-day follow-up period as a result of progression of the underlying disease. No further complications occurred in long term follow-up. CONCLUSIONS: Our results show that the Cliny PEG 13 is a safe technique and an alternative to other methods and surgical procedures in patients in whom a PEG was not applicable by means of the pull-through technique. Larger case numbers and the use in other patient collectives will have to prove these initial results. PMID- 11194882 TI - [Sonography: quo vadis?]. PMID- 11194883 TI - [The ultrasound centre as a medically and economically relevant alternative--a report of the Regensburg experience]. AB - In most medical centres, ultrasonography is performed independently by several departments. In october 1997, the University hospital of Regensburg founded an ultrasound centre, integrating surgical and medical departments as well as the institutes for radiology and nuclear medicine. The aims of this centre were the concentration of organization, machines, financial resources, manpower and know how, standardized training and quality, and strengthening of interdisciplinary cooperation in clinic, medical education and research. Booking, standardized reports and a joint archiving of reports are assisted by a collective computer system. Most examinations in the centre are performed by three all-day present gastroenterology, surgery and radiology residents who are supported by licensed sonographers of the other departments. Training is standardized, and the certification for ultrasound examinations is acquired after a test with theoretical and practical parts. The integration of various departments in the ultra-sound on-call service has led to significant savings. The pool of ultrasound machines is used jointly, department-specific resources for new machines have been put together. We are convinced that this way of a close interdisciplinary cooperation will result in improvements in quality, utilization of financial resources and clinical research. PMID- 11194884 TI - [Successful therapy of hepatorenal syndrome with norepinephrine]. AB - A 39-year-old female with alcoholic cirrhosis was admitted with signs of an alcoholic hepatitis. Within one week a hepatorenal syndrome (HRS) (Creatinin 5.83 mg/100 ml, Harnstoff 235 mg/100 ml) evolved in the absence of additional causes. She had a diminished water (urine volume 31 ml/h) and sodium excretion (10 mmol/l). Urine flow was increased to 131 ml/h by plasma expansion with i.v. infusion of volume and albumin and with infusion of dopamine (3 micrograms/kg/min) and, as there was no diuretic pretreatment and thus, no HRS secondary to diuretic treatment, furosemide (500 mg/24 h). However, impairment of renal function remained unchanged with this therapy. Therefore, norepinephrine (NE) therapy was initiated. A dosage of 0.1-0.12 microgram/kg/min was necessary to achieve the desired increase in the mean arterial pressure of 10-20 mm Hg. During the NE infusion the urine volume increased further to 231 ml/h, the sodium excretion raised to 44 mmol/l, and serum levels of creatinine and urea decreased to 1.91 mg/100 ml and 141 mg/100 ml, respectively. With recovering liver function the NE infusions could be discontinued after 5 days without recurrence of a HRS until discharge after 3 weeks. Beside the vasopressin analogon ornipressin, the combination of norepinephrine and dopamine seems to be useful for the therapy of HRS. Norepinephrine has the advantage of an easy accessibility in ICUs and seems to exert less side effects. PMID- 11194885 TI - [Pulmonal sarcoidosis: A rare side effect of interferon-alpha treatment for chronic hepatitis C infection]. AB - This is a case report of a 44-year-old woman who received a 1-year-treatment with interferon-alpha for chronic hepatitis C virus infection. 3 months after cessation of the therapy she relapsed and was successfully retreated 12 months with a combination of interferon-alpha and ribavirin thereafter. During the treatment the patient developed a typical flue-like syndrome, dry cough with exertional dyspnea that was initially interpreted as a typical side effect of interferon-alpha treatment. Due to the persisting cough, further radiologic and histologic work up was done and results were significant for interstitial sarcoidosis. After interferon-treatment was stopped the pulmonary symptoms resolved completely while pathologic changes in radiographic imaging persisted. Interferon-alpha may have contributed to the development and progression of sarcoidosis by activation of cellular immunity. Although there are only few reports about pulmonary sarcoidosis associated with interferon-alpha treatment, this entity should be included in the differential diagnosis of putative side effects of interferon-alpha therapy. PMID- 11194886 TI - [Ulcers of the colon in association with nonsteroidal anti-inflammatory drugs (NSAID)--a rare cause of gastrointestinal bleeding? Report of 3 cases]. AB - Although adverse side effects of nonsteroidal anti-inflammatory drugs (NSAID) can affect the whole gastrointestinal tract, most reports refer to upper gastrointestinal tract complications. We report on 3 patients with lower gastrointestinal bleeding (patient 1 and 2) respectively detectable fecal blood loss (patient 3) after the use of NSAID. Patient 1 and 3 were taking NSAID over at least 6 months for the treatment of rheumatic diseases while patient 2 reported a single use of 2 g acetylsalicylic acid. Colonoscopy showed a single ulcer of the colon in patients 1 and 2. Due to acute bleeding patient 1 required interventional endoscopic treatment. Colonoscopy of patient 3 revealed multiple colonic ulcerations. Gastroduodenoscopy also detected adverse NSAID-effects on the upper gastrointestinal tract in patient 1 and 3 (ulcers of the stomach, erosive duodenitis). NSAID-medication was discontinued in all patients and, additionally, mesalazine was administered to patient 3. Consecutively, symptoms and lesions disappeared. Our cases stress the clinical importance of NSAID toxicity distal to the small intestine which may exist concomitantly to lesions of the upper gastrointestinal tract and is not obligatory dose-dependent. PMID- 11194887 TI - [Aminosalicylates and aspirin for colonic cancer: from anti-inflammatory to antineoplastic drugs?]. AB - The aim of this article is to review potential antineoplastic properties of anti inflammatory compounds commonly used in various inflammatory diseases such as aminosalicylates, aspirin and other nonsteroidal drugs. Starting from experimental and epidemiologic evidence showing prophylaxis and/or tumor regression/suppression, specific antineoplastic actions especially the inhibition of cyclooxygenase-(COX)dependent and COX-independent steps including the role of transcription factor (NFkappaB) in the cell cycle regulation are reviewed. In addition other mechanisms by which these drugs may exert antitumor effects, also may be important such as induction of apoptosis of cancer cells and/or inhibition of potentially carcinogenic oxidative DNA damage. Based on this knowledge potential clinical implications are discussed. PMID- 11194888 TI - [Therapy of acute pancreatitis. Consensus guidelines]. PMID- 11194889 TI - Stronger association with HLA-Cw6 than with corneodesmosin (S-gene) polymorphisms in Swedish psoriasis patients. AB - Psoriasis vulgaris is strongly associated with certain human leukocyte antigens, especially in early onset. The purpose of this study was to study the HLA-Cw6 allele and its contribution to disease susceptibility in a set of 104 families with at least two affected siblings. A sequencing method was utilized to examine the two exons that build up the antigen binding site of the C locus receptor. DNA from patients homozygous for Cw6 based on haplotype information were sequenced. The results confirmed the identity of the Cw6 allele in affected individuals with the consensus sequence for Cw*0602. We screened the set of families for psoriasis patients homozygous for Cw6 and found 11 individuals with a mean age at onset of 16.1 years. The corresponding figure for the Cw6 heterozygotes was 18.45 years and for the Cw6-negatives 22.36 years. This is indicative of a gene dose effect. We performed a transmission disequilibrium test (TDT) on the Cw6 allele per se, used as a biallelic marker. The analysis resulted in a P-value of 5.3 x 10(-17) (t167/nt45). This greatly exceeds our previous results of a TDT in the region, including microsatellite markers and single nucleotide polymorphisms (SNPs) in the coding part of the S gene (corneodesmosin), which is a suggested candidate gene in the region. The maximum nonparametric linkage (NPL) value was also reached using HLA-C as a marker. We conclude that Cw6 is the allele which shows the highest degree of association with psoriasis in our set of families and we propose that it directly influences the age at onset of the disease rather than increasing the genetic load in accordance with a polygenic theory. PMID- 11194890 TI - Polymorphisms in inflammation genes (angiotensinogen, TAP1 and TNF-beta) in psoriasis. AB - This study focused on the association between plaque psoriasis and polymorphisms of several inflammation genes. Included in the study were 142 Caucasian (Czech) patients with plaque psoriasis and 141 healthy subjects. The genotypes of the polymorphisms in angiotensinogen [M235T ATG, A(-6)G ATG], in transporters associated with antigen processing TAP1 (TAP1*0101, TAP*02011 and TAP1*0301) and in lymphotoxin alpha (TNFbeta) (NcoI in intron 1) were detected by polymerase chain reaction-based methods and restriction enzyme analysis. An increase in B1 (less frequent) allele of NcoI TNFbeta polymorphism was found in psoriatic patients compared to healthy individuals (odds ratio = 1.6, 95% confidence interval 1.13-2.26, P = 0.006). A positive family history of psoriasis was associated with a higher B1 allele frequency in NcoI TNFbeta (P = 0.011). Hardy Weinberg disequilibrium was found in TAP1 polymorphism A-->G at nucleotide 1207 in psoriatic patients. A case-control difference was found in the allelic concurrence of M235T and A(-6)G ATG polymorphisms. The most frequent population genotypes MMGG, MTAG and TTAA were observed in 92% of patients vs 74% of control subjects (odds ratio 0.29, 95% confidence interval 0.14-0.60, P = 0.0003). A positive history of tonsillitis and/or tonsillectomy was associated with a higher T allele frequency of the M235T ATG polymorphism (P = 0.037) as well as with a higher G allele frequency of the A(-6)G ATG polymorphism (P = 0.022). Polymorphisms in proinflammatory angiotensinogen and TNFbeta genes were associated with plaque psoriasis, a positive family history of psoriasis and with frequent tonsillitis in childhood. PMID- 11194891 TI - Animal model of sclerotic skin. III: Histopathological comparison of bleomycin induced scleroderma in various mice strains. AB - We have recently established a mouse model for scleroderma by repeated local bleomycin treatment. In this study, we compared the susceptibility to bleomycin in the development of dermal sclerosis among Balb/c, C3H/He, C57BL/6J, A/J, DBA/2, B10.BR, B10.A, and B10.D2 mouse strains. After either bleomycin or PBS treatment, skin from the injection site was histologically examined. Dermal sclerosis was induced by bleomycin treatment for 4 weeks in all of the strains examined. In particular, C3H/He, DBA/2, B10.D2 and B10.A mice developed intense dermal sclerosis characterized by deposition of homogeneous material in the dermis and thickened collagen bundles. Dermal thickness showed a more than twofold increase following bleomycin treatment, as compared with PBS treatment, except in C57BL/6J and DBA/2 mice. In A/J, C3H/He, B10.A, and B10.D2 mice, dermal thickness showed a more than 2.5-fold increase. Mast cell numbers in sclerotic skin were significantly greater than in PBS-treated skin in Balb/c and B10.A mice after 4 weeks of treatment. We also examined whether bleomycin treatment for 3 weeks could induce dermal sclerosis in C3H mice. Histological examination revealed that epidermal thickness as well as dermal sclerosis was increased in C3H mice following bleomycin treatment for 3 weeks. Increased hydroxyproline content as well as mRNA expression of alpha1(I) collagen, as determined by Northern blot analysis, were observed following bleomycin treatment. Taken together, we conclude that C3H/He and B10.A mouse strains are bleomycin 'susceptible', and these strains are considered to be a suitable experimental model of bleomycin-induced scleroderma. PMID- 11194892 TI - Targeted delivery of DNA encoding herpes simplex virus type-1 glycoprotein D enhances the cellular response to primary viral challenge. AB - Intravenous injection of plasmid DNA encoding herpes simplex virus type-1 glycoprotein D (gD-1) complexed with asialoorosomucoid-poly-L-lysine (gD-ASOR) targets foreign DNA to the liver, leading to hepatic expression of gD-1. BALB/c mice were given two intravenous injections of gD-ASOR, pBK-ASOR (plasmid lacking the gD-1 gene but complexed with ASOR), or PBS. The skin was inoculated with 1 x 10(4) PFU of HSV-1 or sham-inoculated, and analyzed for infectious virus and cellular infiltration 1, 3, and 5 days after inoculation. Prior immunization with gD-ASOR led to significantly lower (P < 0.05) viral titers in the skin 5 days after inoculation compared with controls. Infiltration of the skin at the site of inoculation by polymorphonuclear neutrophils (PMNs), T cells, B cells, dendritic cells, and macrophages was monitored immunohistochemically. Significantly higher numbers (P < 0.05) of CD4+ and CD8+ T cells, dendritic cells, and macrophages responded to HSV-1 challenge in mice immunized with gD-ASOR than in mice immunized with pBK-ASOR or PBS. The response by PMNs and B cells was indistinguishable among the treatment groups. These results suggest that BALB/c mice sensitized to gD-1 following gD-ASOR immunization develop an enhanced T-cell response to primary HSV-1 infection. PMID- 11194893 TI - Comparative inhibitory effects of vitamin D3 and an analogue on normal and psoriatic epidermis in organ culture. AB - Recently, there have been many vitamin D3 analogues synthesized and tried in the treatment of psoriasis. In the experiments reported here we observed and compared their effects on normal and psoriatic epidermis in organ culture in vitro. We employed a new vitamin D3 analogue, 22-oxa-calcitriol (OCT), the effect of which was compared with that of calcitriol (1,25-D3). Both caused suppression of proliferation of normal and psoriatic epidermis, dependent upon concentration and culture time. Histologically, in the presence of the agents, degeneration started from the top of the epidermis downwards. This is the first report of cell degeneration as a direct effect of vitamin D. The nature of the degeneration was evaluated by electron microscopy (EM) and by the in situ nick end labeling technique (TUNEL), and these studies revealed that the degeneration involved necrosis rather than apoptosis. This in vitro method may be useful to assess the effectiveness of newly synthesized vitamin D3 analogues in the treatment of psoriasis. PMID- 11194894 TI - Bleomycin increases steady-state levels of type I collagen, fibronectin and decorin mRNAs in human skin fibroblasts. AB - Bleomycin is a drug capable of inducing tissue fibrosis. In this study, the effects of bleomycin on gene expression of extracellular matrix encoding alpha1(I) collagen, fibronectin and decorin were determined in vitro in human dermal fibroblasts. Northern blot analysis showed that bleomycin upregulated alpha(I) collagen, fibronectin and decorin gene expression dose-dependently between 1 nM and 1 microM. Bleomycin at 100 nM upregulated alpha1(I) collagen, fibronectin and decorin mRNA expression with a peak at 6 h following stimulation in normal skin fibroblast monolayers. Bleomycin enhanced mRNA expression encoding these extracellular matrix proteins in both normal dermal and scleroderma fibroblasts. Concomitant stimulation with bleomycin and interferon-gamma (1,000 U/ml), a representative antifibrotic cytokine, decreased alpha1(I) collagen mRNA expression. Bleomycin also mildly upregulated mRNA expression of transforming growth factor-beta (TGF-beta) and connective tissue growth factor (CTGF) coordinately in normal skin fibroblasts. Our results indicate that bleomycin modulates gene expression of extracellular matrix proteins in dermal fibroblasts, and this effect may be mediated by TGF-beta and CTGF. PMID- 11194895 TI - Vitamin B6 phototoxicity induced by UVA radiation. AB - We have previously reported that pyridoxine shows UVA-induced cytotoxicity. Four other vitamin B6 compounds (pyridoxal, pyridoxamine, pyridoxal phosphate, and pyridoxamine phosphate) are metabolically more important in vivo than pyridoxine. These compounds were examined for UVA phototoxicity to cultured human fibroblasts. The cytotoxicity was measured by post-UVA irradiation colony-forming ability. All the B6 compounds except pyridoxal phosphate showed cytotoxicity. Pyridoxamine phosphate, which is the most important form of vitamin B6 in vivo, had the strongest cytotoxic effect. To examine the involvement of reactive oxygen species in the phototoxicity, we performed an electron spin resonance study using the spin trapping agent, 5,5-dimethyl-1-pyrroline N-oxide, and diethylenetriaminepentaacetic acid. We failed to detect radicals derived from vitamin B6. The cytotoxic effect remained in UVA-irradiated solutions for at least 30 min after the end of UVA irradiation. Hydrogen peroxide was produced in the solution, but the amount was not enough to cause cytotoxicity. In addition, the cells from xeroderma pigmentosum patients who belong to group A or C showed survival curves similar to those of normal fibroblasts. This suggests that cyclobutane pyrimidine dimers or 6-4 photoproducts of DNA were not involved in this damage. These findings suggest that UVA-induced vitamin B6 cytotoxicity is caused by toxic photoproducts resulting from irradiated vitamin B6. PMID- 11194896 TI - Detection of clonal T cells in lichen planus. PMID- 11194897 TI - Immunohistochemical localization of sulfhydryl oxidase correlates with disulfide crosslinking in the upper epidermis of rat skin. PMID- 11194898 TI - The bulge is the source of cellular renewal in the sebaceous gland of mouse skin. PMID- 11194899 TI - Acne chlorina and acne vulgaris--casual likeness or casual homology? PMID- 11194900 TI - Direct contrast-enhanced 3D MR venography. AB - Non-enhanced two-dimensional (2D) time-of-flight (TOF) MRA is well established for imaging of the deep venous system. However, based on the acquisition of multiple axial images, it can be time-consuming and often fails to delineate small superficial and perforating veins. The presented low-dose, direct-contrast injection 3D MR venography technique allows rapid acquisition of high-quality MR venograms and can be employed for the display of the deep and superficial venous system of upper and lower extremity including pelvic and central thoracic veins. This article describes the employed technique and provides a comprehensive image based overview of the various indications for direct-infusion 3D MR venography such as post-/thrombotic changes, varicosities, and assessment of the greater saphenous vein prior to bypass surgery. PMID- 11194901 TI - Blunt trauma of the heart: CT pattern of atrial appendage ruptures. AB - Blunt trauma patients with myocardial ruptures rarely survive long enough to reach a trauma center; however, for the survivors, prompt diagnosis and surgery are mandatory and save up to 80% of patients. Preoperative diagnosis of myocardial ruptures is assessed by echocardiography or, more rarely, by angiocardiography. We report two cases of blunt trauma patients with an atrial appendage rupture which could be retrospectively identified on admission CT survey. PMID- 11194902 TI - Use of half-dose gadolinium-enhanced MRI and magnetization transfer saturation in brain tumors. AB - The aim of this study was to search if half-dose gadolinium (Gd)-enhanced MR imaging with magnetization transfer saturation (MT) can replace standard-dose T1 weighted spin echo (SE) without MT saturation in brain tumors. Thirty patients with a total of 33 brain tumors (14 gliomas, 13 meningiomas, 6 metastases) were prospectively studied using T1-weighted SE half-dose of Gd with MT, and T1 weighted SE standard-dose Gd without MT. The contrast-to-noise ratio (CNR) of the two sequences was calculated and four radiologists reviewed qualitatively the images of the two sequences. There was no significant difference between both techniques for quantitative analysis (Wilcoxon test). However, there was a good agreement between sequences to evidence an intraclass correlation coefficient (r = 0.70) of all lesions. In cases of meningioma, the agreement was better (r = 0.84). The results show a difference in the qualitative data between the two sequences, suggesting the use of the T1-weighted MR images with MT and half-dose of Gd with good results in the whole tested parameters except the lesional edema and the presence of artifacts. Half-dose T1-weighted SE with MT can replace standard-dose T1-weighted SE without MT with no loss of contrast enhancement in investigation of meningiomas and saving 50% of the contrast material. PMID- 11194903 TI - Intracranial aneurysms: evaluation in 200 patients with spiral CT angiography. AB - The goal of this study was to assess the usefulness of spiral CT angiography (CTA) with three- dimensional reconstructions in defining intracranial aneurysms, particularly around the Circle of Willis. Two hundred consecutive patients with angiographic and/or surgical correlation were studied between 1993 and 1998, with CTA performed on a GE HiSpeed unit and Windows workstation. The following clinical situations were evaluated: conventional CT suspicion of an aneurysm; follow-up of treated aneurysm remnants or of untreated aneurysms; subarachnoid haemorrhage (SAH) and negative angiography; family or past aneurysm history; and for improved definition of aneurysm anatomy. Spiral CTA detected 140 of 144 aneurysms, and an overall sensitivity of 97%, including 30 of 32 aneurysms 3 mm or less in size. In 38 patients with SAH and negative angiography, CTA found six of the seven aneurysms finally diagnosed. There was no significant artefact in 17 of 23 patients (74%) with clips. The specificity of CTA was 86% with 8 false positive cases. Spiral CTA is very useful in demonstrating intracranial aneurysms. PMID- 11194904 TI - Multiple glioblastomas: CT and MR features. AB - The aim of this study was to analyze the CT and MR features of multiple glioblastomas, and to determine the best imaging modality for the initial diagnosis. The CT (four exams) and MR imaging (eight exams) of eight patients with proven multiple glioblastomas were reviewed by two neuroradiologists. The lesions were always hypo- or isodense on CT and hyperintense on T2-weighted images (100%). They were usually hypo- or isointense on T1-weighted images (90%). Edema and mass effect were very variable. After contrast media administration, the enhancement was mostly strong (71% on CT and 70% on MR), often either heterogeneous or ring-like. The different lesions of a patient often had a different pattern on MR (75% of cases). Meningeal or ventricular enhancement, suggestive of a possible way of dissemination, was rare. In case of multiple cerebral masses, multiple glioblastomas should be considered as a possible diagnosis in addition to the better known diagnosis of brain metastases, abscesses, or multifocal lymphomas. Moderate edema and mass effect on MR associated with strong and heterogeneous enhancement are suggestive of feature of multiple glioblastomas. Magnetic resonance allows rarely the visualization of a dissemination route. PMID- 11194905 TI - Robust processing of intracranial CT angiograms for 3D volume rendering. AB - The goal of this study was to develop a robust and simple technique for processing of cranial CT angiograms (CTA) in the clinical setting. The method described in this paper involves segmentation of the bone, then dilation of the skull by adding three or four layers of voxels. This dilated skull is subtracted from the vessels object on a voxel-by-voxel basis, allowing segmentation and subsequent display of the vessels only. For evaluation of the technique, three groups of operators processed one CTA, and the quality of the 3D views obtained and the times taken were compared. One group was given training by an expert and a "recipe" for guidance, the second was given only the "recipe," and the third group consisted of expert operators. All operators were able to produce good or acceptable shaded-surface displays when compared with digital subtraction angiography, within 10 min for experienced users, an average of 17 min for trained operators and 26 min for those using only the recipe sheet. Using a simple scoring system for the appearance of feeding vessels and draining veins, no significant differences were found between the three levels of training and experience. This technique simplifies the processing of CTAs and is quick enough to make such examinations part of a routine clinical service. PMID- 11194906 TI - Klippel-Feil syndrome in association with posterior fossa suboccipital dermoid cyst. AB - We present the second case of Klippel-Feil syndrome in association with a posterior fossa dermoid cyst extending through the occipital bone and presenting as a suboccipital subcutaneous mass. We describe its radiographic, CT, and MRI appearances as well as on MRI diffusion-weighted images. Posterior cranial fossa dermoid cysts and sinuses should be added to the list of congenital abnormalities which must be sought in patients with Klippel-Feil syndrome. Diffusion-weighted images of brain may differentiate these masses from cerebral spinal fluid collections. PMID- 11194907 TI - Middle cerebral arterial occlusion in a child with osteopetrosis major. AB - Osteopetrosis major (infantile autosomal recessive type) usually presents with pathological fractures, bone marrow failure and some neurological deficits due to remodelling defect of the bone and narrowed bonny channel of the blood supply. Herein we present a case of osteopetrosis major with neurological deficits not attributed to the narrowed carotid channel of the petrous bone, but due to middle cerebral arterial occlusion 2 cm distal to narrowed channel. PMID- 11194908 TI - The gamut of abdominal and pelvic cystic masses in children. AB - The gamut of abdominal and pelvic cystic masses in children is long with lesions affecting the urogenital tract and retroperitoneum, gastrointestinal tract and mesentery, hepatobiliary tract, and spleen. The goal of this pictorial review is to display the radiological manifestations of these disorders. The radiologist will learn, from this review of the differential diagnosis, how to reach a diagnosis after analyzing the characteristic findings using the appropriate imaging diagnostic studies among the various modalities available in his armamentarium, and the optimal management of these conditions. PMID- 11194909 TI - Prenatal thoracoabdominal tumor mimicking pulmonary sequestration: a diagnosis dilemma. AB - Thoracoabdominal masses are among the many congenital anomalies being detected in fetus. The differential diagnosis of such anomalies include cystic adenomatoid malformation, pulmonary sequestration, neuroblastoma, lymphangioma, congenital diaphragmatic hernia, and bronchial atresia. We report a fetal thoracoabdominal mass that proved to be an angioma that was treated by partial embolization. Complete regression was observed. PMID- 11194910 TI - Quiz case of the month. Osteomyelitis. PMID- 11194911 TI - Diuretic-enhanced gadolinium excretory MR urography: comparison of conventional gradient-echo sequences and echo-planar imaging. AB - The aim of this study was to investigate the utility of different gadolinium enhanced T1-weighted gradient-echo techniques in excretory MR urography. In 74 urologic patients, excretory MR urography was performed using various T1-weighted gradient-echo (GRE) sequences after injection of gadolinium-DTPA and low-dose furosemide. The examinations included conventional GRE sequences and echo-planar imaging (GRE EPI), both obtained with 3D data sets and 2D projection images. Breath-hold acquisition was used primarily. In 20 of 74 examinations, we compared breath-hold imaging with respiratory gating. Breath-hold imaging was significantly superior to respiratory gating for the visualization of pelvicaliceal systems, but not for the ureters. Complete MR urograms were obtained within 14-20 s using 3D GRE EPI sequences and in 20-30 s with conventional 3D GRE sequences. Ghost artefacts caused by ureteral peristalsis often occurred with conventional 3D GRE imaging and were almost completely suppressed in EPI sequences (p < 0.0001). Susceptibility effects were more pronounced on GRE EPI MR urograms and calculi measured 0.8-21.7% greater in diameter compared with conventional GRE sequences. Increased spatial resolution degraded the image quality only in GRE-EPI urograms. In projection MR urography, the entire pelvicaliceal system was imaged by acquisition of a fast single-slice sequence and the conventional 2D GRE technique provided superior morphological accuracy than 2D GRE EPI projection images (p < 0.0003). Fast 3D GRE EPI sequences improve the clinical practicability of excretory MR urography especially in old or critically ill patients unable to suspend breathing for more than 20 s. Conventional GRE sequences are superior to EPI in high-resolution detail MR urograms and in projection imaging. PMID- 11194912 TI - MR imaging findings of uterine endometrial stromal sarcoma: differentiation from endometrial carcinoma. AB - Endometrial stromal sarcoma (ESS) is a rare malignant neoplasm of the uterus. We retrospectively analyzed pelvic MR imaging in 8 cases of ESS to determine the characteristic MR findings of ESS. Magnetic resonance images of 8 cases of ESS were evaluated for findings including the size, margin of the tumor, nodular lesions at the tumor margin, intramyometrial worm-like nodular extension, multiple nodular mass formation, hemorrhage, and necrosis in the tumor. The degree of contrast enhancement was also analyzed. The MR imaging findings of 21 consecutive cases of endometrial carcinoma (EC) were also evaluated and compared with those of ESS. The mean and the standard deviation of the maximum diameter of ESS and EC were 8.80 +/- 4.99 and 3.93 +/- 2.47 cm, respectively. Increased enhancement in at least a part of the tumor was observed in five of the six analyzed ESS cases and in 2 of 12 analyzed EC cases. The irregular margin, nodular lesions at the margin, intramyometrial nodular extension, and multiple nodular mass formation were more frequently seen in cases of ESS than in cases of EC. Magnetic resonance imaging can play a role in both diagnosing ESS as well as in differentiating ESS from EC. PMID- 11194913 TI - Postoperative retroperitoneal hemorrhage due to a bleeding ureteric artery: treatment by transcatheter embolization. AB - We report a case of a postoperative retroperitoneal haemorrhage due to an iatrogenic perioperative injury of an ureteric artery. Transcatheter embolization using microparticles stopped the bleeding and the patient stabilized immediately. Ureteric artery injury is a very rare condition but can be managed successfully by percutaneous interventional techniques. PMID- 11194914 TI - Renal lymphangiomatosis during pregnancy: management with percutaneous drainage. AB - We report a unique case of exacerbation of renal lymphangiomatosis during pregnancy which was managed percutaneously until delivery. Renal lymphangiomatosis is a very rare benign disorder that might cause abdominal pain and rarely hypertension and hematuria. Surgical treatment options may result in nephrectomy. Percutaneous drainage of symptomatic renal lymphangiomas should be viewed as an efficient therapeutic option particularly when surgery is contraindicated. PMID- 11194915 TI - Present-day imaging of patients with renal colic. AB - In the past decade alternatives to urography have been proposed for the study of patients with renal colic. In 1992 it was suggested to replace urography with KUB and ultrasonography. In 1993 the combination of KUB and ultrasonography followed by urography in unresolved cases was proposed and, in 1995, it was suggested to replace urography with unenhanced helical CT (UHCT). This article illustrates the contribution of UHCT to the study of patients with renal colic and analyses advantages and shortcomings of the technique compared with other diagnostic approaches. Diagnostics of the patient with renal colic is based on the detection of direct and indirect signs which allow identification of not only the calculus, with a sensitivity of 94-100% and accuracy of 93-98% according different authors, but also other signs that can serve to guide patient management and evaluate long term prognosis. Unenhanced helical CT has the capability to detect extraurinary abnormalities which present with flank pain and mimic renal colic. The examination technique affects the quality of the images and therefore diagnostic accuracy as well as the dose to the patient. With regard to setting parameters, the choice of thickness and table feed should be guided by numerous factors. Multiplanar reconstruction is indicated in the study of the entire ureter course to identify the exact site of the calcification for the urologist to perform an evaluation similar to that obtained by urography. Many authors consider UHCT to be a valuable tool for suggesting the best therapeutic approach. Among these there are also urologists. The evaluation is based on the stone detection, its size and level in the urinary tract. Cost analysis shows that the cost of UHCT is equal to or inferior to the cost of urography. With regard to the dose, different data are reported in the literature. A high pitch (more than 1.5) and a thin collimation (3-mm thickness) are good compromise between quality and dose which can be compared to the dose of normal urography. What is to be done if helical CT is not available? If helical CT is not available, plain film plus ultrasonography should be considered. This approach does not solve all the cases; in unresolved cases urography is indicated. It should also be noted that US has a good sensitivity in detecting other conditions such as biliary lithiasis, acute pancreatitis, acute appendicitis and abdomino-pelvic masses which are responsible for pain that mimics renal colic. In conclusion, IVU should not have any more the priority in investigating the patients with renal colic. Helical CT should be the first choice in imaging a patient with renal colic. If this technique is not available, plain film and ultrasonography should be considered adding urography in unresolved cases. PMID- 11194916 TI - Virtual endoscopy of the middle ear. AB - Virtual endoscopy is a computer-generated simulation of fiberoptic endoscopy, and its application to the study of the middle ear has been recently proposed. The need to represent the middle ear anatomy by means of virtual endoscopy arose from the increased interest of otolarygologists in transtympanic endoscopy. In fact, this imaging method allows the visualization of middle ear anatomy with high detail, but it is evasive and is essentially used for surgical guidance. Virtual endoscopy provides similar perspectives of the tympanic cavity but does not require the tympanic perforation. In the study of the middle ear, specific attention is given to the retroperitoneum. This region contains elevations of the medial wall (pyramidal eminence and ridge, styloid eminence and ridge, subiculum, ponticulus) and depressions (sinus tympani, posterior sinus tympani, facial sinus, fossula of Grivot, oval window fossula), which can be effectively displayed by virtual endoscopy. Virtual endoscopy is foreseen as a useful tool in preoperative management of patients who are candidates for middle ear surgery, since it can predict with high detail the patient's specific anatomy by imaging perspectives familiar to otosurgeons. PMID- 11194917 TI - 2D and 3D CT imaging correlated to rigid endoscopy in complex laryngo-tracheal stenoses. AB - The aim of this study was to compare 2D and 3D CT imaging in the pre- and postoperative evaluation of complex benign larynges-tracheal airway stenoses with rigid endoscopy, considered as the gold standard. Six patients (aged 5-72 years) with a total of nine complex laryngo-tracheal stenoses underwent non-contrast helical CT scans (slice thickness 3 mm, pitch 1.3, reconstruction interval 1.5 mm) before and after surgical resection. With prototype software, virtual endoscopy (VE) post-processing algorithms were applied to the imaging data sets. The VE and multiplanar 2D findings were compared with rigid endoscopy, considered as standard of reference. All nine stenoses were correctly identified on 3D images and their anatomical locations correctly assessed on 2D reconstructions. Artifacts were met when patients were unable to suspend their breath, leading to one false-positive result. Two-dimensional images and 3D VE of tracheal stenoses proved to be efficient and complementary to the rigid endoscopy, permitting a reliable endoluminal 3D view and evaluation of the surrounding anatomical structures. Limitations of this technique relate to the maximal spatial resolution of 1.5 mm, the lack of color, and the inability to assess the mucosa. Virtual endoscopy is for complex laryngo-tracheal stenoses an excellent complement for rigid endoscopy, remaining the method of reference, and may be indicated with complicated pathological structures. PMID- 11194918 TI - Sinochoanal polyp and its variant, the angiomatous polyp: MRI findings. AB - The angiomatous polyp corresponds to the vascular compromised nasochoanal part of a sinochoanal polyp. We describe the MRI characteristics of such lesions in four patients. All patients had an angiomatous polyp, in three cases as part of an antrochoanal polyp, and in one case as part of a sphenochoanal polyp. The unenhanced MR images depicted the typical appearance of a sinochoanal polyp, hypointense on T1-weighted and hyperintense on T2-weighted images. On gadolinium enhanced MR images, the sinusal part showed little or no peripheral enhancement; however, the nasochoanal part, corresponding to the angiomatous polyp, showed strong enhancement. An angiomatous polyp mimics a hypervascular mass lesion on enhanced MR studies. The anatomic location and association with a sinusal polyp allows the correct diagnosis. PMID- 11194919 TI - Detection of subtle pulmonary disease on CR chest images: monochromatic CRT monitor vs color CRT monitor. AB - To clarify the diagnostic efficacy of color soft-copy computed radiographic (CR) images of the chest in the detection of subtle pulmonary abnormalities. Twenty observers compared 87 soft-copy CR images on four types of CRT monitor (nonmagnified monochromatic CRT, magnified monochromatic CRT, nonmagnified color CRT, and magnified color CRT). Of 87 test images, 45 (including two identical sets of 12 images to test intraobserver variability) were abnormal and 42 (including two identical sets of 12 images) were normal. Of the 45 abnormal images, 15 showed subtle abnormalities, 15 showed mild abnormalities, and 15 showed obvious abnormalities. In the receiver operating characteristic (ROC) analyses, there were no statistically significant differences among the four types of CRT display formats in the detection of subtle abnormalities. Color CRT monitors can replace monochromatic CRT monitors without any loss in the ability to detect subtle interstitial lung disease. PMID- 11194920 TI - Clinically suspected pulmonary embolism: is it safe to withhold anticoagulation after a negative spiral CT? AB - The goal of this study was 3-month clinical outcome in nonanticoagulated patients with clinically suspected acute pulmonary embolism (PE) following a negative spiral CT. During a 6-month period 305 patients underwent spiral CT, of whom only 8 also had a lung scintigraphy. In patients with a final CT report read as not positive for acute PE, all hospital records and answers to a patient questionnaire were analyzed for episodes of venous thrombembolism (VTE). Acute PE was diagnosed at spiral CT in 61 patients (20%). Twenty-six of the remaining 244 patients were excluded from further analysis because of (a) long-term anticoagulation due to symptomatic acute deep venous thrombosis (n = 5), clinically diagnosed acute PE (n = 2), chronic recurrent VTE (n = 4), and cardiac disorders (n = 5); and (b) a normal perfusion scintigram (n = 4) or a negative pulmonary arteriogram (n = 6). Three patients were lost to follow-up. Among the remaining 215 patients only 10 had undergone a negative lower extremity venous study. Sixteen patients (7%) died during the follow-up period, 6 of whom underwent autopsy. Venous thrombembolism was diagnosed in three of the 215 patients (1.4%, 95% confidence limits: 0.5-4.0%), one causing the patient's death. Two patients had advanced thoracic malignancies and the third severe chronic obstructive pulmonary disease (84 years old). A negative spiral CT may be able to exclude clinically significant acute PE with the same accuracy as a normal lung scintigraphy or a negative pulmonary arteriography. PMID- 11194921 TI - Venous hemangioma of the mediastinum. AB - Mediastinal hemangiomas are rare tumors. We present a case of venous hemangioma of the mediastinum. Computed tomography shows anterior mediastinal solid mass without enhancement effects. We believe that it is necessary to include a mediastinal hemangioma for differential diagnosis, when little or no enhancement effects are noted at early and delayed CT examination. PMID- 11194922 TI - Non-bronchial collateral supply from the left gastric artery in massive haemoptysis. AB - Two patients presented with recurrent, massive haemoptysis. Arteriography, including thoracoabdominal aortograms, revealed in both cases large non-bronchial collaterals arising from the left gastric artery. In the first case the non bronchial collateral supplied the upper left lobe and in the second case it supplied the middle right lobe. Percutaneous embolisation of bronchial and non bronchial collateral branches has become an accepted procedure in controlling massive or recurrent haemoptysis. Accurate identification of the non-bronchial collateral arterial feeders is essential for successful embolotherapy. PMID- 11194923 TI - Radiology of the spleen. AB - The spleen is generally not considered a challenge to the radiologist. Most often it poses a problem by anomalies or an irregular but normal contrast enhancement; however, a variety of inflammatory, infectious and neoplastic diseases may involve the spleen. CT and ultrasonography are screening modalities for the spleen. For problem solving, MR imaging can be helpful, especially due to its free choice of the imaging plane and because of the high resolution in contrast MR imaging. Splenic angiography as a diagnostic tool has generally been replaced by CT, ultrasound, or MR and is now used as an interventional method, e. g., in non-surgical management of patients with chronic idiopathic thrombocytopenia or in patients with splenic trauma. This article reviews the radiology of the spleen, including anatomy, embryology, splenomegaly, splenic injury, infarction, cysts, tumors, abscesses, sarcoidosis, and AIDS. Knowledge about the use of different imaging modalities and underlying gross and microscopic pathologic features leads to a better understanding of the radiologic findings. PMID- 11194924 TI - Left-sided omental torsion: CT appearance. AB - A 34-year-old male presented with exquisite left flank pain. Computed tomography showed a hyperdense vascular structure surrounded by whirling linear streaks situated in the greater omentum under the splenic flexure of the colon. Omental stranding extended caudally into the pelvis where part of the inflamed omentum entered a left inguinal hernia sac. Surgery revealed left-sided torsion of the greater omentum. Left-sided omental torsion is infrequent and pre-operative diagnosis is rarely established. The CT findings of an omental fatty mass with a whirling pattern is characteristic of omental torsion. Preoperative diagnosis is important because conservative management has been suggested. PMID- 11194925 TI - Hereditary angio-edema involving the gastrointestinal tract: CT findings. AB - We report a case of hereditary angio-edema in a young man presenting with recurrent abdominal pain for many years. The diagnosis was suspected on the basis of abdominal CT performed during an abdominal attack and was then confirmed by the measurement of serum concentration of C1 esterase inhibitor (C1-INH). To our knowledge, this is the first case reported of the hereditary form of angio-edema with isolated abdominal pain and in which the diagnosis was suggested by abdominal CT findings. PMID- 11194926 TI - Thiamine, beta-cell function and peripheral glucose utilization in thiamine responsive megaloblastic anemia (TRMA) syndrome. PMID- 11194927 TI - Plasma epinephrine and norepinephrine response to stimuli in autonomic neuropathy of type 2 diabetes mellitus. AB - The objective of this study was to examine epinephrine and norepinephrine plasma levels in patients with clinical type 2 diabetes mellitus, at different stages of autonomic neuropathy. Eighteen patients were classified in groups without (n = 6) and with early (n = 6), definite (n = 3) and severe (n = 3) neuropathy. Blood catecholamine levels were measured after the Valsalva maneuver, cold exposure and orthostatic tests. The norepinephrine basal levels were lower in patients with severe neuropathy (0.4 +/- 0.2 nmol/l), compared with the group with no neuropathy (1.3 +/- 0.5 nm/l, p = 0.034), or with early neuropathy (1.3 +/- 0.7 nm/l, p = 0.035). After the Valsalva maneuver, no increase was found in the group with severe alteration. In patients without neuropathy, cold exposure induced a peak of norepinephrine at 5 min (delta = 1.9 +/- 1.6 nmol/l). The increase was lower in groups with definite and severe damage. In patients with definite or moderate neuropathy, the orthostatic test induced minimal or no response. The epinephrine response to the maneuvers was not significant, and no differences were found among the groups. Norepinephrine basal levels and cold responses are diminished in patients with definite and severe autonomic neuropathy. This provides further evidence on their impaired response to stress. The comparable epinephrine levels in patients with or without autonomic neuropathy indicates that adrenal medullar function is not significantly altered. PMID- 11194928 TI - Stress and coping behavior in patients with diabetes mellitus. AB - Diabetes mellitus is a disease which must be controlled over the lifetime of a patient. We investigated the issues of stress and coping for diabetes mellitus which may influence self-management. In addition, we examined the association of these factors with blood glucose control, in order to review self-management instructions for diabetes mellitus. The study included 153 patients with diabetes mellitus. The patients were divided into two subgroups: good-control group, comprising patients with glycohemoglobin (HbA1c) values less than 7.0%; and poor control group, comprising those with HbA1c values of 7.0% or more. All patients responded to a questionnaire regarding stress tolerance, Jalowiec and Power's coping scale and awareness of diabetes mellitus. Stress tolerance was not significantly different between the good-control and poor-control groups. No significant gender differences in coping score were evident for the good-control group. However, in the poor-control group, the coping score in men was significant higher than that in women. The problem-oriented coping score for men in the poor-control group was significantly higher than that for the good-control group (p < 0.01). In a comparison of awareness of diabetes mellitus, the proportion of patients who replied that they were rigidly following diabetes treatment was higher in the poor-control group than the good-control group. Patients with diabetes mellitus may have a knowledge of the disease and a strong will to resolve problems. This is especially true for male patients in that their will appeared to be stronger, but they may not have the resolve to establish appropriate behavior patterns. In the future, methods for evaluating self management should be included in diabetes education. PMID- 11194929 TI - Synergistic effect of arcuate and raphe nuclei graft to alleviate insulinemia and obesity in Zucker rats. AB - The arcuate nucleus (AN) of the hypothalamus is a key area in which endocrine messages are relayed to the brain, while midbrain raphe nucleus (RN) is the source of brain serotonin. Both nuclei contribute to the central mechanism of energy homeostasis. This experiment aimed to determine the impact of AN and RN grafts on insulinemia and obesity in diabetic rats. AN and RN were dissected from 15-day (Fa/Fa) lean embryos and grafted separately or together into the third brain ventricle of obese (fa/fa) male Zucker rats. Histological analysis showed the functional maturity of grafts, which were vascularized, contained neurons reinnervating the periventricular hypothalamus and hypophysis, and expressed neuropeptide Y and enzymes for dopamine and serotonin synthesis. Three months after transplantation, the rats grafted with AN or RN had a lower body weight gain compared to sham-operated rats (19% and 17%, respectively). Rats grafted with AN together with RN gained significantly less body weight than rats grafted with AN or RN separately (31% vs. sham-operated rats), and showed a decreased plasma insulin concentration (132 +/- 33 microU/ml) vs. sham-operated rats (459 +/- 108 microU/ml, p < 0.05). A synergistic effect on alleviating obesity and insulinemia by double AN and RN grafts suggests that both these nuclei are functionally interrelated in maintaining energy homeostasis, and normal functioning of both nuclei is altered during obesity. PMID- 11194930 TI - The effect of aminoguanidine on urinary heparan sulphate levels in experimental diabetes. AB - In the present study, we investigated whether the ameliorating effect of aminoguanidine on diabetes-related proteinuria and nephropathy is associated with glomerular basement membrane heparan sulphate contents. STZ-induced diabetic rats developed proteinuria (at the tenth week: diabetic rats, 713 +/- 418 mg protein per millimole creatinine; control rats, <30) and increased urinary heparan sulphate excretion (diabetic rats, 1,400 +/- 83 microg/mmol creatinine; control rats, 41 +/- 13; p < 0.001), suggesting loss of glomerular basement membrane charge. Aminoguanidine treatment of diabetic rats diminished urinary heparan sulphate levels (196 +/- 52), suggesting high incorporation of heparan sulphate associated charge into glomerular basement membrane. Aminoguanidine administration to diabetic rats also relatively improved proteinuria (456 +/- 255). It is concluded that aminoguanidine treatment has a relative beneficial effect by restoring the diabetes-induced change in renal basement membrane heparan sulphate levels. PMID- 11194931 TI - Resting metabolic rate in Italians: relation with body composition and anthropometric parameters. AB - The objectives of this study were to obtain values for resting metabolic rate in Italians in relation to parameters of body composition, and to compare them to predicted values using the FAO/WHO/UNU equation. We performed a cross-sectional observational study of 131 healthy subjects (46 males and 85 females) at the Human Nutrition Unit, University Tor Vergata, Rome. Body composition was determined by dual energy X-ray absorptiometry (DXA) and resting metabolic rate was calculated using the Weir formula. Resting metabolic rate was 1,865 +/- 234 kcal/day in males and 1,354 +/- 154 kcal/day in females. These values decreased slightly with age. The relationships with weight and age were stronger than that with lean mass from DXA as independent variables in multiple regression analysis. Mean resting metabolic rates predicted with FAO/WHO/UNU and Harris-Benedict formula were not significantly different from measured values except for the Harris-Benedict value for females (p < 0.01). Individual differences between measured and predicted values were notably high. The measured values were higher than those reported in the literature. The prediction of resting metabolic rate is more accurate with simple anthropometric parameters than with fat-free mass obtained by DXA. The individual error in the predicted values can be so high that for individual use a measured value is preferred over an estimated value. PMID- 11194932 TI - Acute effect of physiologic hyperinsulinaemia on serum leptin concentration in healthy young people. AB - This study aimed to identify the acute effect of a physiologic dose of insulin, enough to produce hyperinsulinaemia similar to that obtained in the postprandial state, on serum leptin concentrations in healthy young people. A randomised, single blind controlled clinical trial was performed in 45 healthy, non-obese, young volunteers. Serum leptin concentration, uric acid, creatinine levels and lipid profile were determined for all subjects. Insulin suppression test modified with octreotide, used to produce physiologic hyperinsulinaemia, or saline infusion as control, were performed. Steady state insulin (SSI) concentrations were calculated and they represented the hyperinsulinaemia state. Clinical characteristics and laboratory profiles were similar between groups. There was no significant difference between the effect of insulin or saline infusions on the serum leptin concentration. The acute effect of physiologic hyperinsulinaemia did not modify the serum leptin concentration in healthy young people. PMID- 11194933 TI - Serum concentrations of advanced glycation endproducts are associated with the development of atherosclerosis as well as diabetic microangiopathy in patients with type 2 diabetes. AB - We measured serum concentrations of advanced glycation endproducts (AGEs) in patients with type 2 diabetes, to elucidate the mechanisms underlying the elevated serum concentrations of AGEs and to clarify the relationship between serum AGE concentrations and the development of microangiopathy and macroangiopathy. Serum AGEs were significantly higher in diabetic patients than in age-matched control subjects (p < 0.0001). In diabetic patients, serum AGEs were positively correlated with HbAlc (r = 0.47, p < 0.0001), urinary albumin excretion (UAE) (r = 0.42, p < 0.0001), diabetes duration (r = 0.31, p = 0.0030), and fasting plasma glucose (r = 0.34, p = 0.0010). Multiple regression analysis disclosed that only the HbAlc and UAE levels independently correlated with serum AGE levels. Serum AGEs in diabetic patients with progressive retinopathy and overt nephropathy were significantly higher than in those with less severe retinopathy and nephropathy. Serum AGEs were significantly higher in the diabetic patients with coronary heart disease (CHD) than in those without CHD. These results suggest that the HbAlc and UAE levels are independent risk factors for increased serum AGE concentrations in type 2 diabetic patients, and that higher serum AGE concentrations are associated with increased severity of diabetic retinopathy and nephropathy. Serum AGE concentrations may be a useful marker not only for the severity of diabetic microangiopathy but also for the development of CHD in patients with type 2 diabetes mellitus. PMID- 11194934 TI - Significant association between a silent polymorphism in the neuromedin B gene and body weight in German children and adolescents. AB - Neuromedin B has been shown to exert an inhibiting effect on food consumption in rats. The corresponding gene NMB maps to chromosome 15q22.3-q23, a region expected to contain a gene for the Bardet-Biedl syndrome type 4 (BBS4). Based on its map position and the putative function of the encoded peptide, NMB can be considered as a candidate gene both for BBS4 and the development of human obesity. To examine its involvement in these phenotypes, we determined the genomic structure of human NMB, and performed a mutation screen in its coding region. In genomic DNA of six BBS4 patients and in a large population sample, two sequence variants were detected: a g.253C-->A transversion creating a P73T substitution and a g.401G-->A silent mutation changing the stop codon TGA into stop codon TAA. A case-control study with 92 extremely obese patients and 94 underweight students revealed a significant association between the g.401G-->A polymorphism and body weight (adjustedp = 0.03), which was confirmed in a validation sample consisting of 95 extremely obese patients, and 95 normal weight and 48 underweight individuals (Mann-Whitney p = 0.02). These results suggest a contribution of NMB or a gene in its close vicinity to genetic weight control in humans. PMID- 11194935 TI - New temperature modification makes the Bielschowsky silver stain reproducible. AB - The Bielschowsky silver impregnation can be used as a single stain for the diagnosis of Alzheimer's disease. It impregnates both the amyloid and neuritic components of the senile plaques and it reliably stains neurofibrillary tangles. However, we find that the stain is highly sensitive to changes of the ambient temperature. Since the diagnostic criteria for Alzheimer's disease rely on a semi quantitative assessment of neuritic plaques and neurofibrillary tangles the reproducibility of the Bielschowsky stain is important. In this study we compare three different modifications of the Bielschowsky stain with the methenamine silver stain and with immunohistochemistry for the beta-amyloid and the hyperphosphorylated tau proteins. We found that the most reliable and easily reproducible modification of the Bielschowsky silver impregnation is the one that uses incubations at 5 degrees C. PMID- 11194936 TI - Cyclooxygenase expression in microglia and neurons in Alzheimer's disease and control brain. AB - Epidemiological studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs) lower the risk of developing Alzheimer's disease (AD). Most NSAIDs act upon local inflammatory events by inhibiting the expression or activation of cylooxygenase (COX). In the present study the expression of COX-1 and COX-2 in AD and non-demented control temporal and frontal cortex was investigated using immunohistochemistry. COX-1 expression was detected in microglial cells, while COX-2 expression was found in neuronal cells. In AD brains, COX-1-positive microglial cells were primarily associated with amyloid beta plaques, while the number of COX-2-positive neurons was increased compared to that in control brains. No COX expression was detected in astrocytes. In vitro, primary human microglial and astrocyte cultures, and human neuroblastoma cells (SK-N-SH) were found to secrete prostaglandin E2 (PGE2), especially when stimulated. PGE2 synthesis by astrocytes and SK-N-SH cells was stimulated by interleukin-1beta. Microglial cell PGE2 synthesis was stimulated by lipopolysaccharide only. Although astrocytes are used in studies in vitro to investigate the role of COX in AD, there are no indications that these cells express COX-1 or COX-2 in vivo. The different distribution patterns of COX-1 and COX-2 in AD could implicate that these enzymes are involved in different cellular processes in the pathogenesis of AD. PMID- 11194937 TI - Prenatal exposure to ethanol induces leptomeningeal heterotopia in the cerebral cortex of the rat fetus. AB - Pregnant rats were fed an ethanol-containing liquid diet between gestational day (GD) 10 and GD 21. Leptomeningeal heterotopias were observed in the cerebral cortex of ethanol-exposed fetuses. They appeared on the brain surface of the lateral cortical region near the rhinal fissure, and were found more numerously in the rostral than the caudal region. These abnormalities contained certain neuronal perikarya, microtubule-associated protein (MAP) 1b-positive neuronal processes, and Rat-401-positive radial glial fibers. Immunostaining for Rat-401 revealed that the heterotopias protruded through breaches in the glia limitans. In adult rats exposed to ethanol prenatally, the heterotopias persisted in the lateral cortical region. We conclude that prenatal exposure to ethanol might induce defects in the glia limitans, resulting in the genesis of leptomeningeal heterotopias. These abnormalities may be related to mental retardation or the cognitive deficits associated with human fetal alcohol syndrome (FAS). PMID- 11194938 TI - Neuronal and glial advanced glycation end product [Nepsilon (carboxymethyl)lysine]] in Alzheimer's disease brains. AB - The cellular distribution of an advanced glycation end product [Nepsilon (carboxymethyl)lysine (CML)] in aged and Alzheimer's disease (AD) brains was assessed immunohistochemically. CML was localized in the cytoplasm of neurons, astrocytes, and microglia in both aged and AD brains. Glial deposition was far more marked in AD brains than in aged brains, and neuronal deposition was also increased. On electron microscopic immunohistochemistry, neuronal CML formed granular or linear deposits associated with lipofuscin, and glial deposits formed lines around the vacuoles. Neuronal and glial deposits were prominent throughout the cerebral cortex and hippocampus, but were sparse in the putamen, globus pallidus, substantia nigra, and cerebellum, with glial deposits being far more prominent in AD brains. The distribution of neuronal and glial deposits did not correspond with the distribution of AD pathology. The extent of CML deposits was inversely correlated with neurofibrillary tangle formation, particularly in the hippocampus. Most hippocampal pyramidal neurons with neurofibrillary tangles did not have CML, and most of the neurons with heavy CML deposits did not have neurofibrillary tangles. In the hippocampus, neuronal CML was prominent in the region where neuronal loss was mild. These observations suggest that CML deposition does not directly cause neurofibrillary tangle formation or neuronal loss in AD. PMID- 11194939 TI - Cortical neurons expressing calcium binding proteins are spared in dementia with Lewy bodies. AB - The consistent regional and laminar distribution of cortical Lewy bodies (LB) in brains of patients with dementia with Lewy bodies (DLB) suggests that only a certain subpopulation of neurons develops these alpha-synuclein-immunoreactive cytoplasmic inclusions. This study examined whether four non-overlapping neuronal subpopulations, defined by the expression of non-phosphorylated neurofilaments (SMI-32) and several calcium binding proteins (parvalbumin, calretinin and calbindin D28k), are vulnerable to LB formation. We performed peroxidase immunostaining to examine the distribution and to quantitate each neuronal subpopulation within the superior temporal sulcus (STS) area, and double-label immunohistochemistry to test for colocalization of alpha-synuclein and each neuronal marker in the STS and the entorhinal cortex. There were no significant differences between DLB brains and controls in the proportional quantity or laminar distribution of each neuronal subpopulation. Parvalbumin-immunoreactive neurons represented around 7%, calbindin D28k 8%, calretinin 10%, and SMI-32 about 20% of the total neuronal population in the STS cortex. Neurons expressing parvalbumin and SMI-32 showed a widespread distribution across layers II to VI. Neurons expressing calretinin were present in superficial layers (II to IV), and calbindin D28k-immunoreactive neurons were mostly distributed within granular layers II and IV. None of the LB observed in the STS or the entorhinal cortex were located in neurons expressing calcium binding proteins; 25% of the LB were contained in SMI-32 immunoreactive neurons. In conclusion, cortical neurons expressing calcium binding proteins are spared in DLB, while SMI-32-positive neurons are affected in proportion to their density in the cortex. However, the majority of cortical LB develop in neurons not identified by any of these markers. PMID- 11194940 TI - Spinal tanycytic ependymomas. AB - Three cases of spinal tanycytic ependymoma are reported, a man aged 45 years and two women aged 36 and 55 years. Each patient developed gradual paraparesis over a few months prior to admission. Magnetic resonance imaging showed an enhancing, well-circumscribed tumor in the spinal cord in each case. Histologically, the tumors consisted of monotonous proliferation of long spindle cells with markedly eosinophilic cell processes; focally forming perivascular pseudorosettes. The tumor cells were strongly immunopositive for glial fibrillary acidic protein, S 100 protein and vimentin. Ultrastructurally, in addition to massive intermediate filaments, many tumor cells showed abundant microtubules. Well-developed desmosomes and microvilli/cilia-lined microlumina were occasionally observed. The tumors were grossly totally removed and the patients remain recurrence free at 9, 9, and 2 years postoperatively. Reviewing reported cases including our three cases, tanycytic ependymoma may occur frequently in spinal cord, especially in the cervical region of the spinal cord. Since histologically it resembles pilocytic astrocytoma and schwannoma, tanycytic ependymoma should be included in the differential diagnosis of benign spindle cell tumors of the central nervous system. PMID- 11194941 TI - Prion protein expression in senile plaques in Alzheimer's disease. AB - Prion protein (PrPC) is a glycolipid-anchored cell membrane sialoglycoprotein that localises in presynaptic membranes. Since synapses are vulnerable to Alzheimer's disease (AD), the present study examines PrPC expression in senile plaques, one of the major structural abnormalities in AD, by single- and double labelling immunohistochemistry. Punctate PrPC immunoreactivity is found in diffuse plaques, whereas isolated large coarse PrPC-positive granules reminiscent of dystrophic neurites are observed in neuritic plaques. Finally, PrPC deposition also occurs as dense filamentous and amorphous precipitates in amyloid cores of senile plaques, but not in the walls of blood vessels with amyloid angiopathy. In contrast to PrPC, betaA4-amyloid immunoreactivity is preserved and even enhanced following incubation of the tissue sections with proteinase K prior to immunohistochemistry, thus indicating no PrPC and betaA4-amyloid cross-reactivity in dense amyloid cores of senile plaques. Punctate PrPC deposition in diffuse plaques is similar to that of synaptophysin, a synaptic vesicle-associated protein, as already reported in other studies. Immunoprecipitation, electrophoresis and Western blot studies have shown that synaptophysin, amyloid precursor protein (APP) and betaA4 do not co-precipitate with PrP. These results suggest that synaptophysin, APP and betaA4 are likely not bound to PrP. PrPC accumulation in betaA4-amyloid dense cores may be the consequence of the release of PrP into the extracellular space. Whether PrPC accumulation in the extracellular space is the result of impaired endocytosis and subsequent hydrolysis in the endosomal compartment, in contrast to normal degradation of PrPC, resulting from or occurring in parallel to abnormal APP degradation, deserves further study. PMID- 11194942 TI - Primary involvement of the motor area in association with the nigrostriatal pathway in multiple system atrophy: neuropathological and morphometric evaluations. AB - To evaluate the changes that occur in the motor and supplementary motor cortices in cases of multiple system atrophy (MSA), we carried out morphological and morphometric studies in 7 cases of MSA and 11 age-matched controls. Neuropathological study revealed presence of glial cytoplasmic inclusions (GCIs) in the cortex and subcortical white matter of the motor and supplementary motor areas, loss of small to medium-sized pyramidal neurons, and astrocytosis in the motor cortex in all cases of MSA, showing a definite predilection in the cortical layers V and VI. The severity of neuronal loss in the motor cortex was highly correlated with the incidence of GCIs and the involvement of the nigrostriatal pathway. Morphometrically, significant reductions of both the thickness of motor cortical layers V and VI and the number of neurons were observed. In addition, a reduction in the number of neurons in the supplementary motor cortex was detected in three out of the seven MSA cases. The results of this study suggest that the motor area is a cardinal target in MSA, and that in association with the nigrostriatal pathway it forms a motor loop degeneration in this disease. PMID- 11194943 TI - Heme oxygenase-1 in lesions of human cerebral malaria. AB - Human cerebral malaria is a life threatening complication of Plasmodium falciparum infection. The cascades of signaling events resulting in tissue trauma, lesion formation, coma or resolution of lesions are only slowly becoming unraveled. Understanding the generation of local tissue protective cellular reactions might pave the way for generation of novel drugs limiting the formation of cerebral malaria lesions. Heme oxygenase-1 (HO-1) is an inducible enzyme degrading heme into the gaseous mediator carbon monoxide (CO) and biliverdin, a local antioxidant. Expression of HO-1 is considered a protective reaction against inflammatory and other insults to the brain. We have localized HO-1 to Durck's granulomas, typical lesions of advanced cerebral malaria. Here, activated monocytic cells and ramified microglia in direct vicinity to the lesions express HO-1. The striking association of HO-1 expression with areas of bleedings suggests that released hemoglobin and heme-- known inducers of HO-1--are mainly responsible for induction of monocytic HO-1 expression. HO-1 is expressed rather late to play a protective role in lesion formation and appears to have only a major role in Durck's granulomas. Further, generation of the gaseous mediator CO might contribute to the neurological derangements of advanced cerebral malaria. PMID- 11194944 TI - Autosomal recessive spastic paraplegia with hypoplastic corpus callosum, multisystem degeneration and ubiquitinated eosinophilic granules. AB - We report a 48-year-old woman with familial spastic paraplegia (FSP) showing mental retardation, amyotrophy and sensory disturbance. Her parents were second cousins and there were two other affected siblings in the family. Autopsy revealed degenerative lesions characterized by neuronal loss and gliosis in the upper and lower motor neuron systems, thalamus, lateral geniculate body, dentate nucleus and posterior column of the spinal cord. The remaining neurons often contained ubiquitinated lipofuscin granules. Although the corpus callosum was severely attenuated, it exhibited well-preserved myelination and only minimal gliosis. In the substantia nigra, the number of pigmented neurons was apparently low, but there was slight gliosis and no extraneuronal free melanin pigment in the background. The neurons in this brain region contained much smaller amounts of melanin pigment than might be expected for the patient's age. These findings suggest that this is an example of a family with autosomal recessive FSP with thin corpus callosum, and that maldevelopment of the corpus callosum and substantia nigra is a characteristic feature of the disease. PMID- 11194945 TI - Apoptotic muscle fiber degeneration in distal myopathy with rimmed vacuoles. AB - Rimmed vacuole formation, tubulofilamentous nuclear inclusions and muscle fiber atrophy are the characteristic pathological findings in distal myopathy with rimmed vacuoles (DMRV). Necrotic muscle fibers were few in number and did not appear to account for the muscle weakness, but the nuclear changes with myofibrillar degeneration followed by rimmed vacuole formation appeared to be the major reason for the muscle fiber atrophy in DMRV. To determine whether the nuclear change in DMRV was related to apoptosis, we examined 15 muscle biopsy specimens immunohistochemically, and 7 of them ultrastructurally. The characteristic tubulofilamentous nuclear inclusions were found in 4 and the typical fragmented apoptotic nuclei in 3 of the 7 muscle biopsy samples examined by electron microscopy. TUNEL-positive nuclei reflecting apoptotic DNA fragmentation were found in 13 of 15 biopsies ranging from a few to approximately 1.5% of myonuclei. Apoptosis-specific protein was expressed in the sarcoplasm of atrophic fibers in 13 biopsies both with or without rimmed vacuoles. These findings suggest that the apoptotic process plays a crucial role in myofibrillar degeneration followed by autophagocytosis, i.e., rimmed vacuole formation, in DMRV. PMID- 11194946 TI - [Multidisciplinary approach in the treatment of localized forms of cancer of the prostate]. AB - Localized prostate cancer can be treated by surgery, 3D conformal radiotherapy, brachytherapy: age, clinical stage, Gleason grade, baseline PSA, multidisciplinary approach enable physicians to tailor the therapeutic strategy. Patients are more informed of therapeutic morbidity and health related quality of life and want to give their feeling. Clinical research remains mandatory to set up the treatment policy with more objectivity. PMID- 11194947 TI - [Methods and results of radical prostatectomy for localized cancer of the prostate]. AB - A radical prostatectomy for localized prostate cancer is indicated after evaluation of the disease (initial PSA, clinical stage, biopsy mapping, results of radiologic explorations with an endorectal MRI) and the patient (age, morbidity, life expectancy and wishes of potency conservation). The surgical approaches, retropubic or laparoscopic, depend on the surgeon's experience. Radical prostatectomy provides good disease-free survival for organ-confined disease close to the natural life expectancy. Post-radical prostatectomy morbidity is essentially represented by orthostatic incontinence (up to 6.8%), stress incontinence (up to 27%) and impotence (30 to 95%), depending on the published series and patient age. PMID- 11194948 TI - [Tridimensional conformal radiotherapy of cancer of the prostate]. AB - 3D-conformal-radiation therapy is now available according to progress in imaging and treatment planning. It gives three advantages: better coverage of clinical target volume, decrease of dose in organs at risk and in some cases possibility of escalating the dose in the clinical target volume. These three theoretical advantages are demonstrated for localized prostate adenocarcinomas. An increase of clinical and biological cure rate was demonstrated with 3D-CRT compared with conventional technique for the same dose. A decrease of acute and late complications was observed with 3D-CRT in historical comparisons and in randomized clinical trials. The most exciting point were the results of studies of escalating dose (+10 or 15%). There was a relationship between dose and clinical and biological cure rate. The french study of escalated dose showed a probability of clinical and biological cure rate at 36 months of 50% for doses between 66 and 70 Gy and 85% for doses between 74 and 80 Gy. In conclusion, 3D CRT is becoming more and more important in the treatment of localized prostate carcinoma. PMID- 11194949 TI - The learning curve in prostate seed implantation. AB - OBJECTIVE: To describe the learning curve in prostate seed implantation, according to the experience with two groups of 100 patients. MATERIAL AND METHODS: A perineal, ultrasound-guided implantation technique with manual afterloading was used in all patients. Of a total of 255 patients treated over the period 1989 through 1998, the results of the first hundred patients were compared in relation to the last hundred patients. In the first group single seeds were used, while in the second group RAPID Strands were applied. RESULTS: Although there is a difference in the follow-up period, a significant difference is found in disease-free survival between the two groups. PSA progression was noticed in 39% of patients in the first group and in 12% in the other group. The strongest prognostic factor, however, is the initial PSA value. Toxicity is relatively low, though higher in the second group. CONCLUSIONS: The results obtained in the second hundred patients are in agreement with data from literature. Differences in outcome between the two groups are, however, not only explained by differences in technique, but also by selection and total number of implanted seeds. PMID- 11194950 TI - [Biomodulation and radiotherapy]. AB - Recent improvement in the understanding of the mechanisms involved in the response to ionizing radiation have made it possible to identify new therapeutic targets to increase the anti-tumor efficacy or, alternatively, to decrease the effect on normal tissues. These approaches included targeting genes involved in the regulation of radio-induced DNA-repair and cell death as well as genes involved in the regulation of radio-induced apoptosis. Many other molecular targets have been recently identified to potentially interfere with the response to ionizing radiation, such as some cell membrane growth factor receptors (EGFr, TGFb) or molecules involved in intra-cellular signal transduction pathways, cell cycle regulation, etc. In addition, other promising ways to modulate radiation induced response concern extracellular or tissue factors such as hypoxia and angiogenesis. PMID- 11194951 TI - [Concomitant radiochemotherapy in cancer of the cervix uteri: modifications of the standards]. AB - For a long time, combined external irradiation and brachytherapy has been considered as the standard treatment in patients with advanced cervical cancers. Recently, five clinical randomized trials assessing the role of cis-platin-based chemotherapy delivered concomitantly to radiotherapy have been conducted in the United States. Another clinical randomized trial assessing the role of epirubicin was conducted by the Queen Mary Hospital in Hong Kong. With more than 2,000 enrolled patients, these studies showed converging results with an overall and disease-free survival improvement in the arms combining cis-platin and epirubicin based chemotherapy and irradiation. These combinations led to a significant decrease in loco-regional evolution or recurrence rates, or even in pulmonary metastases rates. The relative risk of recurrences was decreased by 50%. The relative risk of death was decreased by 40%. The differences, however, were less significant in patients with advanced stages III or IVA. Hematological and digestive acute toxicity was significantly higher in the radiochemotherapy groups, but long-term complications were comparable. The results of these randomized trials have led to a modification in the standard of treatment in these poor prognosis cervix cancers. Five of the randomized trials evidenced the superiority of cis-platin-based chemotherapy, but the optimal chemotherapeutic regimens remain to be defined. PMID- 11194952 TI - [Positron emission tomography in thoracic radiography]. AB - The optimisation of the field of irradiation is the aim of the radiotherapist. Pet-Scan provides information revealing a better cartography of node involvement and allowing a better delineation of the tumour zone. In the follow-up of irradiated patients, PET-Scan provides information on the nature of residual lesions and a possible recurrence. PMID- 11194953 TI - [Ewing's sarcoma: towards a common protocol for adults and children]. AB - Ewing sarcoma is an uncommon malignancy that has been frequently managed differently in childhood and adults. This is a review of the international experience that conducted to a common European study called Euro Ewing. This study was launched in 1999. PMID- 11194954 TI - [Brachytherapy in the treatment of vesicoprostatic rhabdomyosarcomas in children]. AB - Brachytherapy has been widely used at the Institut Gustave-Roussy since 1972 in pediatric oncology. In genitourinary rhabdomyosarcoma, because of its ballistic and physical characteristics, it represents the optimal treatment whenever irradiation is required and brachytherapy feasible. Between 1976 and 1998, 23 children with bladder or prostate rhabdomyosarcoma were treated with a protocol including brachytherapy, with five of them treated with a salvage brachytherapy. All but one brachytherapy was performed during the surgery. Among the 18 brachytherapies performed as a first-line treatment, eight presented a tumoral evolution: five presented a local evolution, one a local and nodal evolution and two a nodal evolution. Brachytherapy allowed a conservative treatment among ten out of 11 children alive with no evidence of disease. Among the five patients with salvage brachytherapy, two presented a second recurrence. Sequelae were minimal, consisting of one grade I rectitis and one asymptomatic vesical and ureteral reflux. These results are consistent with the published data using more radical treatment. Brachytherapy can represent an alternative to radical surgery, when indications are clearly defined in bladder or prostate rhabdomyosarcoma. This type of treatment can be performed only integrated with other treatments, more particularly with surgery. This approach requires a close cooperation between the different specialists: pediatricians, surgeons and brachytherapists. PMID- 11194955 TI - [Innovations in the treatment of medulloblastoma]. AB - Prognosis of medulloblastoma remains serious with a disease-free survival rate of 70% at 5 years and severe sequelae in the majority of children. In order to improve this survival rate without unacceptable toxicity, various ways are currently under investigation. Among them, hyperfractionation and conformal therapy seem to be promising. Quality control of radiotherapy treatment could surely also play a major role on outcome. PMID- 11194956 TI - [A century of progress in the knowledge and treatment of nephroblastoma]. AB - Since its initial description by Max Wilms over a century ago, nephroblastoma has benefited from considerable improvements both in terms of basic knowledge about it and management of it. Today, the majority of these very young patients can expect a long-term survival in excess of 90% at the price of a light therapy that combines surgical resection, chemotherapy based on ill-toxic agents, and in selected cases, radiotherapy of remarkably low toxicity. The contribution of large international studies will be emphasized here. PMID- 11194957 TI - [Cancer of the breast: results and toxicity of locoregional irradiation after mastectomy]. AB - The locoregional control is a crucial step in the achievement of a cancer cure. After mastectomy, the locoregional irradiation clearly reduces the chest wall and nodal relapses, especially with initial lesions more than 5 cm or with nodal involvement and/or large lymphatic or vascular emboli. Two recent randomized trials confirmed the benefit of well-adapted locoregional irradiation. In the Danish trial, including premenopausal "high-risk" women treated by mastectomy and chemotherapy (CMF protocol), the radiotherapy reduced the locoregional relapses from 32 to 9% (P < 0.001) and increased the 10-year survival rates from 45 to 54% (P < 0.001). These results are now also confirmed in a postmenopausal group, with an increased 10-year survival rate of 36 to 45% (P < 0.001). In the Canadian trial, locoregional relapse rate decreased from 25 to 13% and 10-year survival rate increased from 56 to 65%. The meta-analysis published in 1995 by the Early Breast Cancer Trialist Collaborative Group (EBCTCG) showed only a modest benefit due to locoregional irradiation in breast cancer. However, when small trials and older trials started before 1970 are excluded due to imperfect methodologies and for inadequate irradiation techniques, the benefit of the "modern" radiotherapy appears significant in the 7,840 patients selected in this way. Thus, since the locoregional irradiation can avoid some metastatic evolutions developed only after "local" or "nodal" relapse, it must be integrated in a multidisciplinary strategy. Nevertheless, this treatment must be safe and this is possible by the use of new techniques, including the definition of anatomical volumes and previsional dosimetry. The most important point concerns the treatment of the internal mammary nodes, especially when previous chemotherapy including anthracyclines was performed. The use of a direct field, with at least 40% of the dose delivered by electrons in an alternating scheme, is recommended to ensure very good protection of the heart and lungs. PMID- 11194958 TI - [Patient positioning and its verification: justification, state of the art of the classical practices]. AB - Patient immobilization is considered an important part of the quality control program in radiation therapy. The need for patient immobilization according to the symptoms, ensuring both reproducibility and comfort, is described in the recommendations for level 1 published by the SFPM (Societe francaise de physique medicale) and the SFRO (Societe francaise de radiotherapie oncologique). A customized device, associated with regular controls, is required for level 2. Customized procedures are mandatory in clinical practice for head and neck and brain treatments. Internal margins and movements of patients must be analyzed and controlled as deviations of CTV placement relative to the isocenter of linacs. They could be reduced with efficient positioning devices and accurate customized immobilization systems. Different devices could be used according to tumor locations. Except for subclavicular tumors, their efficacy remains controversial. PMID- 11194960 TI - [11th National Congress of the French Society of Oncologic Radiotherapy. Paris, France, 23-24 November 2000. Proceedings and abstracts]. PMID- 11194959 TI - [Radiotherapy of cancer of the breast. Technical problems and new approaches]. AB - Technical problems often arise during irradiation to the breast, chest wall, and regional lymph nodes. The following are among the most frequently encountered problems: avoidance of normal tissues (heart and lungs) during chest wall, internal mammary nodes, and large breast irradiations; dose heterogeneity in large breasts; under- or overdosage at field junctions (breast medial tangent and internal mammary fields in particular). Various technical solutions have been offered: modified treatment positions, field inclinations, and conformal irradiation. Many are currently under evaluation. These new technical approaches in breast cancer irradiation require modern facilities for imaging, simulation, and dosimetry, which help to individually design treatment planning. PMID- 11194961 TI - [Assessment of the use of electronic portal imaging]. AB - Improvement in the accuracy of the positioning of the patient during external irradiation is one of the most important issues of the last decades, due to the detrimental impact of the misplacements on treatment outcome. Since 1990, the evolution of the technologic environment has led to a full integration of the portal imaging devices into linac technology. It offers a real on-line verification tool for "high-dose, high-accuracy" treatments. This overview based upon data from the literature describes the different types of imaging devices, the strategies of use and the results obtained. It also considers the use of imaging devices as an in vivo dosimeter. PMID- 11194962 TI - [Image fusion methods for the repositioning of the patient in radiotherapy]. AB - Conformal radiotherapy requires the accurate and reproducible setup of the patient for each fraction delivery. Megavoltage imaging could enable this. This requires the development of image processing and data fusion algorithms. We describe an automated method based on the use of mutual information for registration. Such a method does not require any preliminary segmentation of the images. This method has been extensively tested on phantom as well as on some patient data. The obtained results demonstrated that this automated method for 2D/2D registration is rapid, accurate and robust even in the case of blurred images for small treatment fields. PMID- 11194963 TI - [Is there a future for dosimetry control by portal imaging?]. AB - This article deals with the potential benefits of portal imaging as a tool for the dosimetric control of a radiotherapy treatment. In the introduction the advantages of dosimetric control with portal imaging are described. Subsequently, the physical problem is considered between patient exit dose and dose at the level of the portal detector. Measurements with phantoms have shown that this relationship is complex: different algorithms have been developed by groups of researchers and some of them are summarised in this article. Finally, three examples of dosimetric control using portal imaging are presented: in vivo dosimetry on the beam axis, dosimetric profiles in two dimensions and portal dosimetry for intensity modulation. PMID- 11194964 TI - [The role of surgery in the treatment of glial tumors]. AB - Indications for surgery in the management of glial tumors is twofold. Surgery provides a pathology-based diagnosis that is mandatory in every patient with a clinical diagnosis of glial tumor. However, its role in duration of survival is controversial. Total surgical removal is the best prognostic factor in grade 1 glioma. For grade 2 to 4 gliomas, the results of surgery are variable. Surgical resection is undoubtedly associated with clinical improvement. Its impact on duration of survival is not firmly established, due to, on the one hand, the infiltrative pattern of these types of tumors and, on the other hand, to the inherent difficulty in evaluating their size either pre- or postoperatively. However, the sole clinical improvement related to surgical resection appears sufficient to justify patients' exposure to resective surgery. The surgical risk has dramatically decreased over the last few years mainly due to technical improvements. PMID- 11194965 TI - [Radiotherapy of brain astrocytomas and oligodendrogliomas of the adult]. AB - Gliomas are moderately radiosensitive. The main prognostic factors are the anatomicopathological type and grade of glioma, the performance status, age of the patient and the extent of the surgery. According to data from the literature, high-grade gliomas should be given 60 Gy in five weekly fractions of 1.7 to 2 Gy in a volume including tumor or tumor bed, edema and a 2- to 3-cm margin. A dose of 45 Gy would be sufficient for low-grade gliomas, according to the results of a recent randomized EORTC trial. Brachytherapy and radiosurgery techniques may be indicated in selected cases. PMID- 11194966 TI - [Medical management of malignant gliomas]. AB - The management of patients with malignant glioma aims at improving the duration and quality of life. It rests upon symptomatic (steroid therapy, anticonvulsants, etc.) and specific (chemotherapy, etc.) treatments. It also includes palliative care during the terminal phase of the disease. During the last 15 years, oligodendrogliomas have been demonstrated to be chemosensitive, leading to an improvement of their management; on the other hand, the treatment of glioblastoma multiforme remains disappointing. Development of new research pathways (gene therapy, immunotherapy, antiangiogenic drugs, etc.) feed new hopes for progress in the understanding and management of gliomas during the years to come. PMID- 11194967 TI - [Fractionated radiotherapy of intracranial meningiomas and neurinomas]. AB - In most institutions, surgical excision remains the standard treatment of meningiomas and neurinomas; the aim of surgery is complete resection. However, total removal is not always feasible without significant morbidity and in some cases, the patient's condition contraindicates surgery. For incompletely excised tumors, recurrences will have consequences on neurological functions. There are now many reports in the literature confirming the fact that radiotherapy significantly decreases the incidence of recurrence of incompletely resected benign tumors and that it can replace surgery in some situations where an operation would involve considerable danger or permanent neurological damage: about 80 to 90% of such tumors are controlled with fractionated radiotherapy. Stereotaxic and three-dimensional treatment planning techniques increase local control and central nervous system tolerance so that the respective place of surgery and radiotherapy needs to be redefined, considering efficacy and morbidity of these two therapeutic means. In this article, we limit our remarks to fractionated radiotherapy and, after a review of the literature, we discuss the indications, volume evaluations and the techniques currently used. PMID- 11194968 TI - Combined ozonation and biodegradation for remediation of mixtures of polycyclic aromatic hydrocarbons in soil. AB - A study was conducted to investigate the feasibility of a combined treatment (i.e., ozonation and biodegradation) to overcome the inherent bacterial bioavailability limitation, and hence bioremediation limitation, of polycyclic aromatic hydrocarbons in soil. Ozonation was very efficient in the removal of naphthalene, fluorene, phenanthrene, and anthracene, but not for pyrene, chrysene, and benzo(a)pyrene from soil freshly spiked with the hydrocarbons. A similar result was obtained from coal tar-contaminated soil. Elimination of polycyclic aromatic hydrocarbons increased appreciably in sand containing 0.03% organic carbon, indicating the adverse effect of organic carbon on the efficiency of ozone treatment. In spiked and coal tar-contaminated soils, ozonation followed by biodegradation significantly increased the degradation of various polycyclic aromatic hydrocarbons including chrysene and benzo(a)pyrene which were not degraded by the test bacterial consortium alone. In particular, the effect of the combined treatment was more pronounced in coal tar-contaminated soil than in sterile soil spiked with hydrocarbons, probably due to the augmented biological activity of the introduced consortium. The results suggest that a combined treatment including ozonation and biodegradation may be a promising bioremediation technology in soil contaminated with mixtures of polycyclic aromatic hydrocarbons such as former manufactured gas plant sites. PMID- 11194969 TI - Formation of the metabolic intermediate 2,4,4-trimethyl-2-pentanol during incubation of a Sphingomonas sp. strain with the xeno-estrogenic octylphenol. AB - Degradation of branched octylphenol was studied in a bacterial culture of a Sphingomonas sp. strain. Octylphenol is considered to be the most stable degradation intermediate formed from the corresponding nonionic octylphenol polyethoxylates surfactants during biological wastewater treatment. Since octylphenol can exert estrogenic effects in wildlife, a detailed study of its biodegradation is warranted. The aerobic microbiological transformation of octylphenol was examined with and without the addition of the easily assimilable sodium acetate. In both cases the formation of the metabolite 2,4,4-trimethyl-2 pentanol, representing the intact alkyl chain as a tertiary alcohol, was observed. Since the octylphenol degradation rate was not affected by the presence of acetate, this strain did not show any diauxic metabolic behaviour when incubated with octylphenol and sodium acetate as the sources of carbon and energy. As a result of the biotransformation of octylphenol, its estrogenic potency was removed because it is the phenolic moiety that interacts with the estrogen receptors. This feature opens perspectives for the use of this strain in the framework of an adequate treatment of wastewater with high levels of alkylphenol polyethoxylates. PMID- 11194970 TI - Influence of phenol on biodegradation of p-nitrophenol by freely suspended and immobilized Nocardioides sp. NSP41. AB - The effect of the presence of an alternate toxic compound (phenol) on the p nitrophenol (PNP)-degrading activity of freely suspended and calcium alginate immobilized Nocardioides sp. NSP41 was investigated. In the single substrate experiments, when the concentration of phenol and PNP was increased to 1400 mg l( 1) and 400 mg l(-1), respectively, the initial cell concentrations in the freely suspended cell culture should be higher than 1.5 g dry cell weight l(-1) for complete degradation. In the simultaneous degradation experiment, when the initial concentration of phenol was increased from 100 to 400 mg l(-1), the specific PNP degradation rate at the concentration of 200 mg l(-1) was decreased from 0.028 to 0.021 h(-1). A freely suspended cell culture with a high initial cell concentration resulted in a high volumetric degradation rate, suggesting the potential use of immobilized cells for simultaneous degradation. In the immobilized cell cultures, although simultaneous degradation of PNP and phenol was maintained, the specific PNP and phenol degradation rate decreased. However, a high volumetric PNP and phenol degradation rate could be achieved by immobilization because of the high cell concentration. Furthermore, when the immobilized cells were reused in the simultaneous degradation of PNP and phenol, they did not lose their PNP- and phenol-degrading activity for 12 times in semi continuous cultures. Taken together, the use of immobilized Nocardioides sp. NSP41 for the simultaneous degradation of PNP and phenol at high concentrations is quite feasible because of the high volumetric PNP and phenol degradation rate and the reusability of immobilized cells. PMID- 11194971 TI - Distribution in the environment of degradative capacities for gasoline attenuation. AB - A methodology allowing the detailed assessment of the capacities of microflorae to degrade gasoline in aerobic conditions has been developed. It consisted in the determination of the degradation of a gasoline model mixture in liquid cultures in optimal conditions. The gasoline model mixture contained 23 representative hydrocarbons of gasoline (GM23). The kinetics and extent of biodegradation were evaluated by continuous overall monitoring of CO2 production and final chromatographic analysis (usually after about 30 days) of the consumption of each hydrocarbon. The methodology was used with soil and water samples from polluted and non polluted sites. The experimentation aimed at assessing the distribution of the degradative capacities in the environment and the prospects for natural attenuation of gasoline. Nine microflorae were tested. The intrinsic biodegradability (existence of mechanisms of biodegradation) appeared total for GM23 as shown by the results obtained with several microflorae. The degradative capacities of microflorae from non polluted samples were high (total degradation rates at least 85%). Incomplete degradation was observed essentially for trimethylalkanes (2,2,4-trimethylpentane and 2,3,4-trimethylpentane) and for cyclohexane. In several cases, samples from polluted sites exhibited more extensive degradative capacities, with total degradation of all hydrocarbons being observed for three out of the six samples. PMID- 11194972 TI - Investigating the specificity of regulators of degradation of hydrocarbons and hydrocarbon-based compounds using structure-activity relationships. AB - Microbial biosensors which have genes for bioluminescence coupled to genes that control hydrocarbon degradation pathways can be used as reporters on the specificity of regulation of those pathways. Structure-activity relationships can be used to discover what governs that specificity, and can also be used to separate compounds into different groups depending on mode of action. Published data for four different bioluminescent biosensors, reporting on toluene (two separate biosensors), isopropylbenzene, and octane, were analyzed to develop structure-activity relationships between biological response and physical/chemical properties. Good QSARs (quantitative structure-activity relationships) were developed for three out of the four biosensors, with between 88 and 100 per cent of the variance explained. Parameters found to be important in controlling regulator specificity were hydrophobicity, lowest unoccupied molecular orbital energies, and molar volume. For one of the biosensors, it was possible to show that the biological response to chemicals tested fell into three separate classes (non-hydrocarbons, aliphatic hydrocarbons, and aromatic hydrocarbons). A statistically significant QSAR based on hydrophobicity was developed for the fourth biosensor, but was poor in comparison to the other three (44 per cent variance explained). PMID- 11194973 TI - Degradation of o-methoxybenzoate by a two-member consortium made up of a gram positive Arthrobacter strain and a gram-negative Pantotea strain. AB - Aromatic carboxylic acids substituted with methoxylated groups are among the most abundant products in "alpechin", the wastes resulting from pressing olives to obtain olive oil. Degradation of o-methoxybenzoate by an stable consortium made of a gram positive bacterium, Arthrobacter oxydans, and gram negative one, Pantotea agglomerans, was shown to mineralize this compound efficiently. The concerted action of both microorganisms was needed for the two first steps in the process, namely, the conversion of o-methoxybenzoate into salycilate, and the hydroxylation of the latter to gentisate. Gentisate was further degraded by the Arthrobacter strain. PMID- 11194974 TI - Anaerobic utilization of essential oils by denitrifying bacteria. AB - Plant volatile organic compounds are a major carbon source in nature. We studied the degradability of these substances by anaerobic microorganisms in enrichment cultures with representative essential oils as organic substrates and nitrate as electron acceptor. Lemon and pine needle oil supported microbial growth in the presence of pure oil, whereas parsley seed, camphor, sage, fennel, and mint oil supported growth only when the essential oils were dissolved in an overlying phase of 2,2,4,4,6,8,8-heptamethylnonane. Thyme oil did not support denitrification. Analyses of the microbially degraded oils revealed the disappearance of monoterpenes, of several monoterpenoids, and of methoxy-propenyl benzenes, including apiole and myristicin. Most-probable-number determinations for denitrifying communities in sewage sludge and forest soil yielded 10(6) to 10(7) monoterpene-utilizing cells ml(-1), representing 0.7 to 100% of the total cultivable nitrate-reducing microorganisms. The utilization of essential oils together with the common occurrence of this metabolic trait are indications for an environmentally important, but currently unexplored anaerobic turnover of plant volatile organic compounds in soil. PMID- 11194975 TI - Enhancement of hydrocarbon waste biodegradation by addition of a biosurfactant from Bacillus subtilis O9. AB - A non-sterile biosurfactant preparation (surfactin) was obtained from a 24-h culture of Bacillus subtilis O9 grown on sucrose and used to study its effect on the biodegradation of hydrocarbon wastes by an indigenous microbial community at the Erlenmeyer-flask scale. Crude biosurfactant was added to the cultures to obtain concentrations above and below the critical micelle concentration (CMC). Lower concentration affected neither biodegradation nor microbial growth. Higher concentration gave higher cell concentrations. Biodegradation of aliphatic hydrocarbons increased from 20.9 to 35.5% and in the case of aromatic hydrocarbons from nil to 41%, compared to the culture without biosurfactant. The enhancement effect of biosurfactant addition was more noticeable in the case of long chain alkanes. Pristane and phytane isoprenoids were degraded to the same extent as n-C17 and n-C18 alkanes and, consequently, no decrease in the ratios n C17/pri and n-C18/phy was observed. Rapid production of surfactin crude preparation could make it practical for bioremediation of ship bilge wastes. PMID- 11194976 TI - Bacterial growth based on reductive dechlorination of trichlorobenzenes. AB - An anaerobic mixed bacterial culture was enriched for bacteria dechlorinating 1,2,3- and 1,2,4-trichlorobenzene (TCB) to dichlorobenzenes by exclusive use of non-fermentable substrates and the application of vancomycin. Growth and dechlorination occurred in a purely synthetic medium with formate or hydrogen, acetate, and TCB. Neither acetogenesis nor methanogenesis was detected in the culture. Repeated subculturing maintaining high dechlorinating activities was also achieved when only hydrogen and TCB were supplied. This indicated that reductive dechlorination of TCB was the primary energy conservating process. The number of dechlorinating bacteria was strictly limited by the amount of TCB supplied in the medium. In addition, the dechlorinating activity could be maintained only in the presence of TCB. A most probable number analysis showed that the dechlorinating species amounted to at least 6 x 10(5) cells per ml at a total cell number of about 2 x 10(6) cells per ml. Vitamin B12 significantly stimulated the dechlorinating activity. PMID- 11194977 TI - [Propofol and remifentanil in day surgery]. AB - BACKGROUND: AIM OF THE STUDY: to compare AG versus MAC using propofol & remifentanil in a day surgery setting evaluating intra and postoperative clinical conditions and emergence times. METHODS: Propofol and remifentanil, either for general anesthesia (AG) then conscious sedation (MAC), have been administered to 218 patients undergoing mainly plastic or proctologic surgery as day hospital. AG was induced with propofol 1.5-2 mg/kg followed by a continuous infusion of 10 mg/kg/h and remifentanil infused at 10 micrograms/kg/h; MAC was started with propofol 3 mg/kg/h and remifentanil 4-5 micrograms/kg/h; during the maintenance phase of both AG and MAC, infusion rates of both drugs were adjusted according to clinical needs. Diazepam (0.05-0.06 mg/kg) and/or midazolam (2-3 mg) were given as premedication or coinduction as necessary. All patients received field infiltration with local anesthetics (lidocaine or mepivacaine); patients under GA were artificially ventilated with O2/air through IOT or LMA. Surgical and anesthesiological data were collected on specially designed records, with special attention to time intervals between anesthesia (FA) and surgery (FC) end and eyes opening (EO), orientation (OR), return of spontaneous breathing (SR), extubation (EST), sitting (SED), walking (CAMM), dressing (VEST) and discharge (DIM); data were analyzed with parametric and non parametric analysis of variance. RESULTS: All emergence intervals were longer under AG than under MAC: the earlier in the range of 4-5 vs 0.5-1 min; for the late intervals; FA-SED 24 +/- 18 vs 15 +/- 8, FA-PIED 65 +/- 48 vs 34 +/- 17, FA-VEST 69 +/- 58 vs 33 +/- 17, FA-CAMM 68 +/- 42 vs 39 +/- 19. Discharge times (83 +/- 67 vs 73 +/- 60) were similar between the two groups. Drugs consumption under AG were roughly double than under MAC; total dose infused of propofol (mg/kg/min) 0.118 +/- 0.044 vs 0.06 +/- 0.036; total dose of remifentanil (microgram/kg/min): 0.106 +/- 0.049 vs 0.066 +/- 0.027. AG resulted in a higher % incidence of intraoperative hypotension and bradycardia: hypotension 61.7 vs 25.7 and bradycardia 30.3 vs 12.4. SaO2 decreased more commonly during MAC than AG (20.9% vs 10.1); intraoperative itching was referred in 20% of MAC patients. Conversions rate from MAC to AG was 2.8%. Psychomotor agitation was more frequent following AG (14%) than MAC (2%); nausea (1%), vomiting, shivering (12%), headache (2%), ortostatic hypotension (2%) were similar between the two groups. Diazepam and/or midazolam caused a significant prolongation of recovery intervals, for both AG and MAC with a mean delay of the order of 100-200%. CONCLUSIONS: Propofol- remifentanil gave excellent conditions for a wide variety of day surgery procedures, offering good anesthesia with quick emergence; the addition of bdz, even at low doses, prolongs significantly discharge times. PMID- 11194978 TI - Why anaesthesia is a good model to study respiratory system. PMID- 11194979 TI - Clinical comparison of either small doses of fentanyl or remifentanil for blunting cardiovascular changes induced by tracheal intubation. AB - BACKGROUND: To compare in a prospective, randomized study the effects on cardiovascular changes after tracheal intubation produced by small doses of either remifentanil or fentanyl. METHODS: With Ethical Committee approval, after intravenous midazolam premedication (0.05 mg.kg-1), 30 normotensive, ASA physical status I-II patients, without cardiovascular or respiratory diseases, and with a Mallampati score < 2, were randomly allocated to receive an intravenous bolus of either 3 micrograms.kg-1 fentanyl (n = 15) or 1 microgram.kg-1 remifentanil (n = 15) infused over 60 sec and followed by a 0.15 microgram.kg-1.min-1 continuous intravenous infusion. General anesthesia was then induced with propofol (2 mg.kg 1), followed by atracurium besilate (0.5 mg.kg-1) to facilitate tracheal intubation. Following intubation, the lungs were ventilated mechanically using a 60% nitrous oxide in oxygen mixture with a 1% inspired fraction of sevoflurane. Arterial blood pressure and heart rate were recorded before anesthesia induction (baseline), one minute after induction of anesthesia, immediately after tracheal intubation and every minute for the first five minutes after intubation. RESULTS: Systolic arterial blood pressure values were significantly higher in the Fentanyl than in the Remifentanil group patients from 2 to 5 min after tracheal intubation (p < 0.01), while no differences were observed between the two groups in either diastolic arterial blood pressure or heart rate values. Four patients in the Remifentanil group (26%) but only one patient in the Fentanyl group (7%) showed systolic blood pressure values < 90 mmHg during the study period (p = not significant); however, the observed decreases in systolic arterial blood pressure values were transient and did not require treatment for any subject. CONCLUSION: We conclude that in healthy normotensive patients, the control of cardiovascular responses to tracheal intubation obtained with a 1 microgram.kg-1 loading dose of remifentanil is more effective than that provided by a 3 micrograms.kg-1 bolus of fentanyl, with the advantage of no risks for postoperative respiratory depression. PMID- 11194980 TI - [Non-invasive positive pressure mechanical ventilation in acute respiratory failure]. AB - Known for two centuries, positive pressure non invasive mechanical ventilation (VMNPP) has been widely applied in acute respiratory failure (IRA) only in the last ten years. The fact that VMNPP is able to improve gas exchange by avoiding endotracheal intubation and its complications is the most attractive aspect in both general and respiratory intensive care units and in the respiratory ward. Characteristics of VMNPP (interface, ventilator and modality of ventilation), the side where it is performed as well as severity of IRA, underlying disease, and the team's experience are important factors which influence outcome. The addition of VMNPP to conventional medical therapy reduces the need for IE, mortality and hospitalisation in a selected population of BPCO patients in IRA. As there are no available data for comparison between invasive mechanical ventilation (VMI) and VMNPP, the latter has not to be considered as an alternative to VMI but able to prevent it and, even if VMNPP fails, it may be used as a weaning technique. In IRA due to other than BPCO diseases VMNPP seems not to be more effective than standard treatment in avoiding IE but it may give efficient support with fewer complications as compared to VMI. Acute cardiogenic pulmonary edema and "terminal" diseases represent some of the most interesting application fields of VMNPP in non-BPCO patients. According to the latest literature data, in this review history, technique, advantages, limits, indications, nursing and cost of VMNPP are examined. PMID- 11194981 TI - [Systemic review of trials on the use of tramadol in the treatment of acute and chronic pain]. AB - BACKGROUND: The purpose of the study was to verify the effectiveness of tramadol in the treatment of non-oncologic chronic pain, oncologic chronic pain and postoperative acute pain, applying the principles of meta-analytic analysis to randomized clinical trials (TCR). METHODS: I: Medline research of the TCR on the question in the period between 1989-1999, II: exclusion of single TCR through the question of Moore and Mcquay; calculation of the relative risk reduction (RRR), of the number needed to treat (NNT), of the odds ratio (OR) and of the typical odds ratio (TOR) of the trials which responded to characteristics of correct randomization and blindness, which expressed citation of the patients excluded from trial, and patients with measurable analgesic effectiveness (number of patients with reduction of the pain intensity 50%). RESULTS: 52 trials extracted from Medline: 10 on the treatment of non-oncologic chronic pain, 36 on the treatment of postoperative acute pain and 6 on the treatment of oncologic chronic pain. Responded fully to requirements: 8 studies (3 for non-oncologic chronic pain, 3 for postoperative acute pain and 2 for oncologic pain). The OR was 0.55 ( 0.31/1.41); 0.44 (1.04/1.92) and 0.98 (0.5/1.46); the RRR was 0.26 (-0.19/0.71), 0.38 (0.15/0.61), 0.005 (0.19/0.20) and the NNT 6.6 (6.39/6.81), 5.26 (5.12/5.4), infinity in the 3 trials selected between those that concern the treatment of the nononcologic chronic pain (with TOR: 0.57 and confidence index: 0.23-0.9); the OR was 0.36 (1.06/1.78), 0.78 (-0.08/-1.64) and 1.12 (0.54/1.69); the RRR was 0.26 ( 0.18/0.7), 0.07 (-0.2/0.35), -0.01 (-0.09/0.07) and the NNT 4.7 (4.42/4.58), 20 (19.8/20.20), infinity in the trials on the treatment of postoperative acute pain (with TOR: 0.4 and confidence index: -0.6-0.86); the OR was 0.53 (-0.67/1.73), 0.27 (-0.71/1.12); the RRR was 0.19 (-0.33/0.72), 0.35 (0.02/0.68) and the NNT 7.1 (6.78/7.42), 3.57 (3.37/3.76) in those that involved the treatment of oncologic chronic pain (with TOR: 0.49 and confidence index: 0.36-0.8). CONCLUSIONS: Although the short number of trials which can treated by the metanalytic technique the treatment with tramadol, compared comparison's to drugs (morphine, pentazocine, bupremorphine, etc.) determined a slight improvement in analgesic parameters or at least in analgesic effectiveness. PMID- 11194982 TI - European Committee for Hyperbaric Medicine (ECHM) to coordinate, promote and study the development of clinical hyperbaric medicine in Europe. PMID- 11194983 TI - Ketorolac for paediatric postoperative pain. A review. AB - Ketorolac, a nonsteroidal anti-inflammatory drug (NSAID) largely used in adults, deserves particular attention for postoperative pain therapy in children, even if it is not officially approved for paediatric use. We have examined a lot of studies about the use of ketorolac for paediatric postoperative pain, pointing out pharmacological and pharmacokinetic properties and side effects. There are significant differences in pharmacokinetic parameters, doses, routes of administration, length of treatment, side effects, usage precautions and pharmacological interactions between children and adults. Amongst the many drugs available, ketorolac seems to be particularly efficient for postoperative pain therapy in children too. PMID- 11194984 TI - Assessment of immunological status in the critically ill. AB - The systemic inflammatory response (SIRS) results from various types of injuries such as severe infection, trauma, ischemia-reperfusion and major surgery including cardiac surgery with cardio-pulmonary bypass. This response involves immune cell activation and a complex network of proinflammatory cytokines, which may induce multiple organ failure when uncontrolled. The monocyte plsys a central role in the response to infection with the release of TNF-alpha, IL-1 beta, and IL-12. In addition, monocytes present antigens to T lymphocytes. An optimal antigen presentation requires the expression of MHC class II HLA-DR on monocytes surface and of costimulatory molecules such as CD54 on monocytes and LFA-1 on lymphocytes. It has become increasingly apparent that the proinflammatory response is balanced by concomitant anti-inflammatory mechanisms that results in monocyte deactivation, characterized by a decrease in HLA-DR expression and the release of anti-inflammatory cytokines such as IL-10. This counterregulatory response, if prolonged or predominant, may predispose the patient to a higher risk of infection. Further studies need to be conducted to precise: i) the intensity of depression of the surface molocule expression assessing monocyte function, such as HLA DR and CD54; ii) the level of IL-10 and IL-12 release in patients with severe sepsis; iii) the immuno-modulating effects of frequently used treatments in these patients with severe sepsis and in surgical patients; iv) the time course of recovery; v) if the monitoring of HLA-DR, CD54, IL-10 and IL-12 will better predict the clinical outcome than clinical parameters. PMID- 11194985 TI - [Thrombotic thrombocytopenic purpura (TTP) or Moschowitz syndrome. Our experience]. AB - AIM: The aim of this study was to report that Moschcowitz's syndrome was an inexorable cause of death in our Centre in the cases we observed, all of which failed to respond to the treatment used. This severe prognosis was attributed to the irreversible nature of the pathology when the patients were admitted to intensive care. METHODS: Three cases are described which were brought to our attention with this pathology. The following association was present in all cases: low platelet count, anemia with schistocytosis and indirect hyperbilirubinemia. Plasmapheresis was the main treatment used in all cases. SETTING: the intensive care unit of our Hospital is the regional reference centre where plasmapheresis is performed. PATIENTS: Three patients were studied: two females aged 62 and 42 respectively, and one male aged 63. All three patients came from this region and no special features were found in their long-term medical history. INTERVENTIONS: all patients underwent blood transfusion, plasmapheresis and received targeted antibiotic and corticosteroid treatment, and parenteral nutrition. RESULTS: All three cases died. CONCLUSIONS: The analysis of these cases highlights the need for an early diagnosis, even if this is not easy, in order to commence successful therapy. PMID- 11194986 TI - [Low backache: toward practice guidelines?]. PMID- 11194987 TI - The role of arterial elastance in ventricular-arterial coupling in normal gravity and altered acceleration environments. AB - The role of physiological elastance (Ep) in maximizing external work (EW) transfer is not well understood and has not been investigated during microgravity and increased acceleration conditions. By better understanding this relationship, cardiovascular control mechanisms for meeting metabolic demands during normal gravity and altered acceleration stresses may be elucidated. Therefore, the objectives of this study were to determine the effect of Ep in maximizing EW of the left ventricle and to investigate this relationship during altered acceleration states. Ventricular and arterial parameters were estimated using established lumped parameter models from isolated beats of experimental data. These data were obtained during parabolic flight (0 and approximately 2 Gz) and centrifuge runs (approximately 1 to approximately 4 Gz) where acceleration was used to drive the cardiovascular system into a wide range of physiologic operating and coupling conditions. Parameter estimates at each Gz level were used in a series of computer simulations in which Ep was varied over a wide range to find the point of maximum EW for that coupling condition. Cardiac output and mean arterial pressure were maintained throughout the simulation process by adjusting heart rate. Results of the simulation showed that as arterial elastance decreased from its initially estimated (physiologic) value, external work increased slightly and as elastance increased, external work decreased. In particular, we found that the arterial elastance was set at a point near that which would produce maximal external work. In addition, it was found that altered Gz states may affect the Ep-EW relationship. PMID- 11194988 TI - The effects of age and sex on susceptibility to motion sickness. AB - BACKGROUND: The present investigation is concerned with the role of sex, age and experience in determining motion sickness susceptibility. HYPOTHESIS: Motion sickness susceptibility varies with sex and age, and may be related to the level of physical activity sustained by the individual. METHODS: Three surveys were conducted. The first included school age children (9-18 yr) and addressed motion experience and motion sickness on 13 forms of transport. The second questionnaire sought to determine whether these sex differences could be understood in terms of differential involvement in various forms of physical activity. The third survey addressed the role of age and sex effects in a college age population. RESULTS: The first study revealed significantly greater motion sickness for female as compared with male subjects on devices with which both groups were equivalent in terms of exposure history. The second study showed little relation between an individual's level of physical activity and susceptibility to motion sickness. The results of the third study were in essential agreement with the first survey and revealed no significant interactions between age and sex, suggesting that sex differences remain stable across this age range. CONCLUSION: Our conclusions regarding these surveys are that sex differences in motion sickness do not vary significantly with age and cannot be accounted for by differences in exposure to motion or physical activity. There was also little evidence for the notion that men are more reticent to report motion sickness. PMID- 11194989 TI - Positive end expiratory pressure (PEEP) slightly modifies ventilatory response during incremental exercise. AB - To clarify the ventilatory effects of a 5-cm H2O positive end expiratory pressure (PEEP) in healthy men during incremental exercise in normoxic conditions, 22 subjects were subjected to a constant workload (0 W, 50 W, 100 W, 150 W and 200 W) on a cycle ergometer for periods of 8 min each, both with and without 5-cm H2O PEEP. Results show that PEEP increases inspiratory (TI) and expiratory (TE) duration and tidal volume (VT) and decreases breathing frequency (fB) at rest (p < 0.05). During exercise, TI is higher at 50 W and 100 W (p < 0.05), but not at 150 and 200 W. TE only increases at 50 W (p < 0.05). An increased VT (p < 0.05 at 50, 100 and 150 W) and a decreased fB (p < 0.05 throughout the experiment) were observed. However, mean inspiratory flow (VT/T1) and duty cycle (TI/TT) were unaffected by PEEP. In conclusion, this study shows that a 5-cm H2O PEEP slightly modifies the ventilatory parameters in healthy subjects during incremental exercise in normoxic conditions. PMID- 11194990 TI - Energy cost of physical task performance in men and women wearing chemical protective clothing. AB - BACKGROUND: Chemical protective clothing (CPC) is required to perform certain occupations and is known to inhibit physical performance. Few data are available that quantify the physiological response of men and women during task performance while wearing CPC. HYPOTHESIS: The mobility of a task will have a significant effect on the change in energy cost. The energy cost of wearing CPC will be greater in women than men during physical task performance. METHODS: Energy cost (VO2) and the psychophysical scales, rating of perceived exertion (RPE) and respiratory distress (RD), were measured in 32 men and 26 women during the performance of 31 physical tasks. Tasks were categorized by mobility: stationary, intermittent or continuous. Between 6-12 men and 5-13 women conducted each task wearing 2 clothing conditions: battle-dress uniform (BDU, wt = 3.7 kg) and (CPC, wt = 9.3 kg). RESULTS: VO2 L x min(-1), was higher in CPC compared with BDU for the continuous task category for both genders. However, when VO2 (ml x kg(-1) clothed wt x min(-1)) was normalized for clothing weight, there remained a significant clothing effect for the continuous category, but there were no gender differences. VO2, expressed as a % VO2max, was significantly increased for BDU compared with CPC for the continuous task category only. This difference was significantly greater for women than men. Women exercised at a higher % VO2max and reported a higher RPE than men for all categories in both BDU and CPC. Both genders reported higher RD wearing CPC for the continuous task category only. CONCLUSIONS: There is an increase in energy cost wearing CPC during continuous tasks which can be attributed to both the clothing weight and the hobbling effect. Wearing CPC is more physiologically and psychologically demanding for women than men, especially when performing tasks of a continuous nature. PMID- 11194991 TI - Heat strain imposed by toxic agent protective systems. AB - This study evaluated physiological heat strain from two developmental toxic agent protective systems compared with the standard Toxicological Agent Protective (TAP) suit during exercise-heat stress. Eight subjects (six men, two women) completed three experimental trials, at 38 degrees C, 30% rh, wearing: 1) Self Contained Toxic Environment Protective Outfit (STEPO) with rebreather (STEPO-R); 2) STEPO with tether (STEPO-T) or 3) the standard TAP. The STEPO systems provided effective body cooling of: STEPO-R, 200 +/- 36 W; and STEPO-T, 186 +/- 59 W. TAP had no cooling. All experimental trials used treadmill walking at 0.89 m x s(-1), 0% grade at exercise/rest cycles of 20/10 min for 240 min. Metabolic rates for the treatments were: STEPO-R, 298 +/- 26 W; STEPO-T, 299 +/- 34 W; and TAP, 222 +/- 40 W. Rate of heat storage was less (p < 0.05) in STEPO-R (37 +/- 8 W x m( 2)) and STEPO-T (38 +/- 12 W x m(-2)) than in TAP (77 +/- 15 W x m(-2)). Sweating rate was less (p < 0.05) in STEPO-T (10.0 +/- 4.8 g x min(-1)) than in TAP (23.8 x 11.4 g x min(-1)). There was no difference between STEPO-R (12.3 +/- 5.6 g min( 1)) and the other two uniform systems. Subjects did not complete targeted exposure times of 240 min. Exposure time was longer (p < 0.05) in STEPO-R (83 +/- 22 min) and STEPO-T (106 +/- 39 min) than in TAP (46 +/- 10 min). Predicted time to 39.0 degrees C was less (p < 0.05) in TAP (69 +/- 20 min) than in either STEPO R (226 +/- 124 min) or STEPO-T (244 +/- 170 min). The results of this study show that cooling in STEPO significantly reduced heat storage relative to TAP. The new generation toxic cleanup uniform systems effectively reduced heat stress and increased work capabilities compared with the standard TAP suit. PMID- 11194992 TI - Determination of lumbar muscular activity in helicopter pilots: a new approach. AB - BACKGROUND: Discomfort in the lumbar region is a frequent complaint of helicopter pilots. Two factors that helicopter crewmembers relate to back pain are exposure to vibration and poor posture during flight, because during flight the seat and controls force the pilot to adopt an asymmetric posture. Repeated exposure to these adverse flight conditions could cause pathological changes in the spine. The purpose of this study was to compare right and left sided lumbar muscular activity in helicopter pilots under real flight conditions, using surface electromyography (SEMG) to demonstrate the effects of asymmetrical posture on the musculoskeletal system. An attempt was also made to correlate lumbar muscular activity with environmental factors and such variables as type of flight, type of helicopter, duration of flight, age, physical fitness, and height. METHODS: Right and left-sided lumbar electrical activity were measured using two-channel SEMG during 35 flights in 2 types of helicopter and a cockpit mock-up. RESULTS: There was a statistically significant increase in right-sided lumbar activity when related to the duration of flight. CONCLUSIONS: The data showed that when the pilot used the manual controls during flight, he did not maintain a symmetrical posture and contracted one side more than the other. We think the relationship between the greatest right-sided contraction and flight duration is due to maintaining an asymmetric posture over a long period. We also noted a tendency towards greater right lumbar musculature activity in older pilots. PMID- 11194993 TI - Impact evaluation of the Royal Australian Air Force health promotion program. AB - BACKGROUND: In 1981, the Royal Australian Air Force (RAAF) introduced an intensive health promotion program (HPP), the purpose of which was to control preventable diseases, particularly cardiovascular disease (CVD), linked to lifestyle-related risk factors. However, the RAAF HPP's effectiveness had not been appropriately evaluated since its implementation. HYPOTHESIS: The RAAF HPP's interventions have reduced, beyond secular trends, the prevalence of lifestyle related CVD risk factors. METHODS: Retrospective cross-sectional risk factor prevalence surveys of randomly selected RAAF pilots and navigators were conducted for the years 1980, 1983 and 1989. The survey results for RAAF subjects were compared with the results obtained for demographically similar subjects participating in National Heart Foundation (NHF) Risk Factor Prevalence Study (RFPS) surveys for the same periods, using chi2 and Mantel-Haenszel (M-H) chi2 tests, and 1-way and 2-way ANOVA. RESULTS: Over the survey periods, the prevalence of overweight and obesity decreased by 8% in RAAF subjects and increased by 7% in NHF subjects, and mean total serum cholesterol decreased by 8% in RAAF subjects while remaining static in NHF subjects. Participation in vigorous physical activity increased among RAAF, but not NHF, subjects. The results for most other risk factors showed significant differences between RAAF and NHF subjects, but trends were comparable over survey periods. CONCLUSIONS: On balance, reductions in the prevalence of overweight and obesity, and mean serum cholesterol in RAAF subjects were probable effects of the RAAF HPP. Other observed differences in CVD risk factors between RAAF and NHF groups were attributable to the RAAF aircrew selection process, or other RAAF-specific influences. The study thus provides qualified support for the hypothesis, although effects were less evident in older RAAF subjects. PMID- 11194994 TI - Factors associated with pilot error in aviation crashes. AB - BACKGROUND: The importance of pilot error in aviation crashes has long been recognized. However, understanding and preventing pilot error remains the foremost challenge in aviation safety. OBJECTIVE: This study aims to identify pilot characteristics and crash circumstances that are associated with the presence of pilot error in a large sample of aviation crashes. METHODS: Different data files compiled by the National Transportation Safety Board for 329 major airline crashes, 1,627 commuter/air taxi crashes, and 27,935 general aviation crashes for the years 1983-96 were merged; and the presence of pilot error was analyzed in relation to variables indicating the characteristics of the pilot-in command, crash circumstance, and aircraft. Multivariate logistic regression modeling was performed to assess the associations of individual variables with the likelihood of pilot error given a crash. RESULTS: Pilot error was a probable cause in 38% of the major airline crashes, 74% of the commuter/air taxi crashes, and 85% of the general aviation crashes. Among the factors examined, instrument meteorological condition and on-airport location were each associated with a significantly increased odds of pilot error. The likelihood of pilot error decreased as pilot certificate rating increased in commuter/air taxi and general aviation crashes. Neither pilot age nor gender was independently associated with the odds of pilot error. With adjustment for pilot characteristics and crash circumstances, flight experience as measured in total flight time showed a significant protective effect on pilot error in general aviation crashes. CONCLUSIONS: The prevalence and correlates of pilot error in aviation crashes vary with the type of flight operations. Adverse weather is consistently associated with a significantly elevated likelihood of pilot error, possibly due to increased performance demand. PMID- 11194995 TI - Age and risk-taking in French naval crew. AB - The purpose of this study was to evaluate the effects of age in French naval crew on risk-proneness. We tested 130 male navy personnel, age range 19-41 yr, with EVAR, a visual analog scale designed to rate risk-proneness and composed of 24 items distributed among 5 factors: "self control," "danger-seeking" "energy," "impulsiveness," and "invincibility." We observed a significant negative correlation between "energy" and age, whereas the other factors were not influenced by age. Risk-proneness change is limited and should not be a safety issue in the decision-making process if the age of navy crews is going to increase moderately. PMID- 11194996 TI - Louis H. Bauer, M.D., and the first civil U.S. aeromedical standards: his continuing legacy. AB - Louis Hopewell Bauer, M.D. (1888-1964) promulgated the first civil aviation medicine regulations for U.S. civil airmen on December 31, 1926. Major elements of these regulations are reflected in the current Federal Aviation Administration Civil Airman Medical Standards, these latter including modifications resulting from medical and aeronautical technical advances. Dr. Bauer's plans covering periodic examinations, waivers, and a system implemented through designated "Aviation Medical Examiners" are continued to this day. Dr. Bauer founded the progenitor of the present Aerospace Medical Association in 1929, the Aero Medical Association. Further, he founded the Journal of Aviation Medicine, the predecessor of the present Aviation, Space, and Environmental Medicine journal, the first issue published in March, 1930. Dr. Bauer's influence in medicine broadened to include the presidency of the American Medical Association (1952-3) and a long standing leadership role with the World Medical Association. His 1926 textbook, Aviation Medicine, stands as an historic centerpiece in the evolution of aviation medicine. Bauer's leadership and contributions to civil aviation medicine came at the right time to enhance the development of U.S. civil aviation and civil aviation safety. PMID- 11194997 TI - The experience of nausea during sustained hyper-gravity flight with negligible angular velocity. PMID- 11194998 TI - Fatigue modeling. PMID- 11195000 TI - Operational physiology in the U.S. Navy. PMID- 11194999 TI - Brief exposure to -Gz reduces cerebral perfusion pressure during subsequent +Gz stress in rats. AB - INTRODUCTION: In humans, +Gz exposure immediately preceded by exposure to zero or -Gz can result in unexpected incapacitation ("push-pull" effect). Our goals were to establish whether this phenomenon exists in rats and to evaluate the importance of varying the duration of -Gz exposure on magnitude of the push-pull effect on cerebral perfusion pressure. METHODS: Eight conscious male rats were studied in the transition from +5 Gz to +10 Gz imposed by centrifugation. This was done with (push-pull) or without (control) 2 s exposure to -5 Gz applied using a counterbalanced design. Seven isoflurane anesthetized rats were studied in the transition from 0Gz (+1Gy) to + 1Gz imposed by tilting. This was done with (push-pull) or without (control) 0.5, 1, 3, or 9 s exposure to -1Gz imposed immediately prior to the transition applied using a counterbalanced designed. RESULTS: Exposure to 2 s of -5 Gz significantly (p < 0.01) reduced carotid artery pressure in the 4th through 8th s of exposure to +10 Gz by an average of 15 mmHg compared with control. In the tilt experiments, a push-pull effect was found with mild Gz exposure (+/-1Gz) with as little as 0.5 s -Gz exposure. Varying the head down dwell time did not alter the magnitude of the exaggerated hypotension induced by "push-pull" (p = 0.90). CONCLUSIONS: We conclude that rats express a "push-pull" effect similar to that observed in humans but that altering the duration of exposure to -Gz does not influence the magnitude of the "push-pull" effect. PMID- 11195001 TI - Tumour vaccines: a new immunotherapeutic approach in oncology. AB - Substantial progress has been made in vaccine development in recent years for the treatment of malignant diseases. New technologies have fostered the identification of potentially immunogenic tumour antigens that can be used to activate the patient's immune system to specifically recognize and destroy human tumour cells. More detailed insights into the process of intracellular protein degradation, processing and cell surface presentation have allowed immunogenic peptide domains to be identified that can be used in vaccine trials. Still a matter of intensive debate is the question of the most optimal presentation of tumour-derived proteins or peptides to the immune system to achieve a maximum response. In this area, major progress has been made by using dendritic cell or even naked DNA-based vaccines. The generation of new tools such as HLA-tetramer complexes now allows researchers to monitor more closely the expansion of peptide specific T cells under the process of vaccination. On the basis of these advances, a couple of vaccine trials have been performed that have increased our knowledge of vaccine development and provided indications that the concept of tumour-specific vaccination might be valid. However, we are still at the beginning of this process and should always remember that only well-designed, prospective clinical trials can define the optimal use of tumour vaccines in oncology. PMID- 11195002 TI - Effects of interferon-alpha2b treatment on ex vivo differentiation of mast cells from circulating progenitor cells in a patient with systemic mastocytosis. AB - Interferon (IFN)-alpha, a known inhibitor of myelopoiesis, is increasingly used to treat patients with systemic mastocytosis (SM). However, the mechanisms of IFN alpha effects on mast cell (MC) growth remain unknown, and the treatment responses may be variable. In the present study, factor-dependent ex-vivo differentiation of MCs from peripheral blood mononuclear cells (PBMNCs) was analyzed in a patient with SM treated with IFN-alpha2b (3 million U/day). The patient exhibited an extensive MC infiltration in his bone marrow (BM) and increasing serum total tryptase levels (spiking to > 1,400 ng/ml). PBMNCs were collected before and during IFN-alpha2b treatment and cultured in the presence or absence of stem cell factor (SCF, 100 ng/ml) for 42 days. In the absence of SCF, no MC growth was detectable. However, in the presence of SCF, MC containing tryptase appeared in the cultures. Treatment with IFN-alpha2b resulted in a time dependent decrease in SCF-inducible formation of MCs from PB progenitor cells in vitro. Also, during IFN-alpha2b treatment, blood histamine concentrations decreased. Serum total tryptase levels initially increased despite IFN-alpha2b treatment. However, after a latency period of a few months, tryptase concentrations declined and then reached a plateau. In healthy individuals, the SCF-induced in vitro growth of MCs from their progenitor cells was also inhibitable by the addition of IFN-alpha2b. In summary, our data show that IFN alpha2b can exhibit inhibitory effects on factor-dependent growth of MC progenitor cells. However, it still remains open which of the patients with mastocytosis can benefit from long-term IFN-alpha treatment. PMID- 11195003 TI - GP130 and c-kit signalling, initiated by the sIL-6R/IL-6 complex, is insufficient to expand the primitive adult bone marrow CD34+CD38- pre-CFU cell. AB - It has previously been shown that gp130 and c-kit signalling synergize for the ex vivo expansion of human cord blood (CB) CD34+ haematopoietic progenitor cells. We were interested in evaluating this synergy within an ontogenetically different haematopoietic tissue [i.e. adult bone marrow (BM)] and on a more primitive progenitor subset (i.e. CD34+ CD38-cells), which are highly enriched for pre colony forming unit (CFU) cells. These cells were plated out in a primary liquid culture supplemented with either interleukin (IL)-6+stem cell factor (SCF), IL-6+ SCF+soluble IL-6 receptor (sIL-6R), IL-6+SCF+sIL-6R+IL3+IL-1 or SCF+IL-3+IL-6+IL 1. Cell counting after liquid culture revealed an absolute expansion of 2.2-, 4.1 , 89.5- and 65.7-fold compared with initial cell input for the four-cytokine combinations, respectively. The secondary read-out assay revealed that this cell expansion in the liquid culture also resulted in CFU generation, with absolute cloning efficiencies of 0.002, 0.024, 12.13 and 7.73 (per cell initially present) for the respective cytokine combinations. These results indicate that gp130 and c kit signalling alone (i.e. using IL6+SCF+sIL-6R), in terms of both cell number and CFU generation, insufficiently stimulate primitive adult BM CD34+CD38- haematopoietic cells in order to reach a CFU generation comparable with that obtained after multifactor stimulation. Adding sIL-6R to the multifactor stimulation and compared with this multifactor stimulation, a 1.7-fold synergy in terms of cell expansion and a 3.0-fold synergy in terms of CFU generation are obtained. The sIL-6R/IL-6 complex thus has a narrower spectrum of action on primitive adult BM CD34+CD38- cells than on CB CD34+ cells. PMID- 11195004 TI - Immunoelectron microscopic analysis of CD 54 surface distribution and its role in homotypic interaction on normal monocytes and blasts of acute myeloid leukemia. AB - The role of CD 54 in the homotypic interaction of normal monocytes and the blasts of five cases of acute myeloid leukemia (AML) was analyzed by immunoelectron microscopy (IEM). The cells were seeded on glass coverslips precoated with an electrontransparent melamine resin, which allowed their in situ labeling with monoclonal antibodies (MoAb) and subsequent analysis by whole mount immunoelectron microscopy (WM-IEM) or transmission immunoelectron microscopy (TIEM). Timed incubation of the cells in serum-free medium +/- interferon-gamma (IFN-gamma, 500 U/ml) induced a spreading of the monocytes and the blasts of four out of five leukemias, characterized by the development of numerous filopodia which led to initial cell-cell contacts. In parallel, an increase in CD 54 surface density in four out of five leukemias could be detected, while no evidence of a CD 54 redistribution (capping) on single cells could be observed. WM-IEM studies detected no CD 54 molecules in the "early" cell-cell contacts, while "later" cell-cell contacts displayed strong CD 54 positivity. These data indicate that CD 54 is not involved in initial cell-cell contacts but is shifted secondarily to the cell contact sides and may thereby stabilize the adjacent membrane areas. The absence of spreading of the CD 54 negative blasts in one out of five leukemias and the blockade of the cellular migration by an anti-CD 54 MoAb (Clone 84H10) in the remaining cases suggest that CD 54 expression is necessary for cellular locomotion. The observed inhibitory effect of the anti-CD 54 MoAb probably mimics a negative circuit that serves to control cellular migration. PMID- 11195005 TI - Successful autologous bone marrow rescue in patients who failed peripheral blood stem cell mobilization. AB - We assessed autologous bone marrow (BM) harvest and hematologic recovery after high-dose chemotherapy (HDCT) in patients who failed to achieve peripheral blood stem cell (PBSC) mobilization. One hundred and ninety-three patients with germ cell tumor, malignant lymphoma, sarcoma or medulloblastoma were scheduled for HDCT. In 123 patients, PBSC were mobilized by disease-specific chemotherapy plus granulocyte colony-stimulating factor (G-CSF). In 110/ 123 patients (89%) with circulating CD34+ cell counts 2 > or = 10/microl, sufficient hematopoietic autografts were collected (group A). In 13/123 patients (11%) with peripheral CD34 + cell counts < 10/microl, PBSC harvesting was not performed (group B). These latter patients were classified as "poor mobilizers" and underwent second line BM harvest at a median of 46 (range 10-99) days after mobilization failure. Seventy patients with first-line BM harvest (group C) acted as historical controls. Ten patients from group B proceeded to HDCT and nine were evaluable for hematopoietic reconstitution. Recovery to neutrophils >0.5 x 10(9)/l was comparable with group C patients: 16 (range 9-34) days vs 13 (range 8-98) days. However, platelet (PLT) reconstitution >20 x 10(9)/l was significantly slower, with a median of 35 (range 13-50) days as compared with 19 (range 9-148) days (P = 0.0106) for control patients. Supportive care requirements, febrile days and length of hospital stay were not significantly different between the two groups of patients. We conclude that patients who fail to mobilize PBSC should be evaluated for second-line BM harvest. This approach may preserve the therapeutic option of HDCT for these patients. PMID- 11195006 TI - Plasma kinetics of an artificial emulsion resembling chylomicrons in patients with chronic lymphocytic leukemia. AB - Chylomicrons are the lipoproteins that transport dietary lipids in the blood. Although neoplastic diseases are often accompanied by alterations in lipid metabolism, chylomicrons are scarcely explored in cancer, despite their importance for the body's energy supply. Moreover, no data are available regarding chylomicron metabolism in chronic lymphocytic leukemia (CLL). Chylomicron metabolism in the bloodstream consists of lipolysis by lipoprotein lipase and uptake of remnants by the liver and is difficult to assess in the human body. Among the methods to evaluate this pathway, the determination of the plasma kinetics of triglyceride-rich emulsions that mimic chylomicrons is a practical and straightforward approach. A double-labeled chylomicron-resembling emulsion was injected into 10 patients with CLL and into 11 normolipidemic healthy subjects. The plasma kinetic curves of the emulsion 3H-triglyceride and 14Ccholesteryl ester were determined in plasma samples collected over 30 min. The fractional clearance rate (FCR) of triglycerides in CLL was not changed compared with controls. The FCR of cholesteryl esters was also no different from controls. These results indicate that chylomicron lipolysis and remnant removal are not affected in CLL. PMID- 11195007 TI - Intracranial hemorrhage in children with immune thrombocytopenic purpura. Japanese Study Group on childhood ITP. AB - We sent questionnaires to hospitals in Japan in order to study the incidence and conditions of intracranial hemorrhage (ICH) in children with immune thrombocytopenic purpura (ITP). From 1980 to 1995, 11 cases of ICH were reported in eight patients with ITP at 35 institutions. One patient had ICH four times, but only one patient died of the condition. From 1990 through 1995, ICH occurred in four (0.52%) of 772 patients with ITP. None of the patients died. The platelet count when ICH occurred was 5.2 +/- 3.7 x 10(9)/l (mean +/- SD) (n = 11). Four of the eight patients (1980-1995) had received active treatment [e.g. intravenous immunoglobulin G (i.v. IgG)] immediately before ICH occurred. In seven cases (1980-1995), possible causes of ICH, including menstruation (n = 2) and viral infections (n = 3), were identified. Systemic lupus erythematosus (SLE) later developed in three patients. Although the incidence of ICH in children with ITP has not decreased compared with the rates in earlier studies, the mortality rate has decreased markedly. Our results suggest that menstruation, infection, and risk factors for progression to SLE may help to predict ICH in children with ITP. Large-scale prospective trials are needed to identify risk factors for ICH. PMID- 11195008 TI - Acute respiratory distress syndrome following intrathecal methotrexate administration: a case report and review of literature. AB - Acute Respiratory distress syndrome (ARDS) is a rare complication following intrathecal (IT) injection of methotrexate (MTX) in adult acute lymphoblastic leukemia (ALL) patients. A 19-year-old man with ALL developed strikingly acute respiratory failure during central nervous system (CNS) prophylaxis with IT MTX administration and cranial irradiation. Histopathologic study of the lungs revealed a pattern of diffuse alveolar damage with interstitial cellular infiltration. His symptoms were relieved soon following treatment with corticosteroids and the pulmonary infiltrates resolved gradually. Pulmonary symptoms did not recur as he was continuously treated with oral corticosteroids. PMID- 11195009 TI - Lymphoma of bone with initial presentation as a calvarial mass. AB - A 21-year-old man was examined for a right frontal skull mass that had been present for 4 months. Excision biopsy of the mass revealed diffuse large B-cell lymphoma. Subsequent studies showed right preauricular lymphadenopathy but no systemic involvement. The patient was treated with six courses of CHOP (cyclophosphamide, adriamycin, vincristine, and prednisolone) with adjuvant whole brain irradiation and achieved a complete remission. PMID- 11195010 TI - Complete remission of generalized relapsed extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type of the gastrointestinal tract after high-dose chemotherapy and autologous peripheral stem cell transplantation. AB - Due to their homing properties, extranodal marginal zone B-cell lymphoma (MZBL) of mucosa-associated lymphoid tissue (MALT) type remain localized for long periods of time, and therefore have an excellent prognosis. However, if generalization and/or transformation into a diffuse large-cell lymphoma occurs, the prognosis deteriorates and no established treatment concepts are yet available. We report about a 57-year-old female patient with relapsed transformed stage-IV extranodal MZBL of MALT type of the entire gastrointestinal tract who was successfully treated using salvage chemotherapy followed by BEAM conditioning [BCNU 1,3-bis-2-(chloroethyl-1-nitrosourea), etoposide, cytosine arabinoside, and melphalan] and autologous peripheral stem cell transplantation. Follow-up revealed a sustained complete remission for 22 months. PMID- 11195011 TI - Treatment of supraventricular tachycardias in the new millennium--drugs or radiofrequency catheter ablation? AB - Supraventricular tachycardias are a cause of significant morbidity in children. Newer anti-arrhythmic drugs and the invention of radiofrequency catheter ablation have revolutionised anti-arrhythmic therapy in children. CONCLUSION: With the availability of these very effective therapeutic options, an improved knowledge of these methods and their indications is required. PMID- 11195012 TI - Cerebral spinal fluid flow, venous drainage and spinal cord compression in achondroplastic children: impact of magnetic resonance findings for decompressive surgery at the cranio-cervical junction. AB - In order to investigate the diagnostic properties of MRI of the brain and spine in achondroplastic children with regard to decompressive surgery, 25 patients were examined by conventional morphological and by "functional" imaging of CSF flow and magnetic resonance angiography (MRA) of the veins and sinuses at the cranial base following a special protocol. The results were compared to those from age-matched controls and were correlated with each other and retrospectively with the neurological findings. Measurements of distances and angulations at the cranio-cervical junction (CCJ) from MR scans showed similar values to those from conventional radiographs and CTs and thus can be used without correction for spatial distorsion. Signs of cervical medullary compression, myelomalacia and intramedullary cyst formation were found in six, seven and three children respectively. These alterations correlated significantly with each other (P < 0.05). Semiquantitative evaluation of CSF flow demonstrated interruption of CSF pathways at the CCJ, which correlated with CCJ narrowing (P < 0.05). MRA showed a significant narrowing of the jugular foramina with a variable compensatory enlargement of the emissary veins and a significant reduction of the total outflow area (P < 0.01). There were no significant correlations between these MR changes and neurological deficits. CONCLUSION: Due to this unexpectedly poor correlation between magnetic resonance and clinical findings in achondroplastic children, the present role of magnetic resonance in the clinical setting is limited to the demonstration of spinal cord compression in individual cases. In three of our patients with prominent neurological abnormalities, the severe changes demonstrated by magnetic resonance imaging strongly supported the indication for surgical decompression. PMID- 11195013 TI - Effects of enzyme replacement therapy in thirteen Japanese paediatric patients with Gaucher disease. AB - To determine treatment effects in the unique and previously internationally unreported Japanese paediatric patient population with Gaucher disease (GD), we analysed six response parameters among 13 patients given enzyme replacement therapy (ERT). Also to obtain insights into optimising maintenance dosing, through subgroup analysis we retrospectively examined effects of three ERT dose reduction schedules from a starting regimen of 60 U/kg of body weight every 2 weeks. Our patients included 11 males and two females, 11 individuals with possible type 1 and two individuals with type 3b GD, six individuals with the L444P/F2131 genotype and five with the L444P/L444P genotype, and five who had been splenectomised. Despite different mutation prevalence, Japanese patients with GD, like their counterparts from other ethnic groups, generally benefitted from ERT. However, early and marked ERT dose reduction (from 60 U/kg to 30 or 15 U/ kg every 2 weeks within < or =6 months) was associated with insufficient improvement of mean haemoglobin level and relative height and with insufficient improvement or worsening of platelet count. Only the subgroup given 60 U/kg of ERT every 2 weeks for 36 months had significant improvement in mean haemoglobin, platelet count, angiotensin-converting enzyme and acid phosphatase levels and relative height at 36 months. CONCLUSION: These data suggest that long-term high dose enzyme replacement therapy may be required to obtain sufficient improvement to maintain health among paediatric patients with severe Gaucher disease. PMID- 11195014 TI - Clinical presentation of congenital sialidosis in a patient with a neuraminidase gene frameshift mutation. AB - Congenital sialidosis is a rare lysosomal storage disease caused by a primary neuraminidase deficiency which results from defects in the neuraminidase gene on chromosome 6p. The inheritance is autosomal recessive. Patients exhibit excessive urinary excretion of bound sialic acid and decreased or undetectable amounts of neuraminidase activity in various tissues. The clinical expression is variable, but ascites and hepatosplenomegaly are hallmarks of the disease. Skeletal abnormalities, facial dysmorphism and inguinal herniae have been described in most of the few reported cases. We describe a baby girl with biochemically proven sialidosis, who in addition to the above clinical features, had severely dilated coronary arteries, excessive retinal vascular tortuosity and an erythematous, macular rash. Homozygosity for a frameshift mutation at residue 623 of the neuraminidase cDNA was found. We speculate that the additional features found in our patient might be associated with the here described genotype of congenital sialidosis. CONCLUSION: Severely dilated coronary arteries, excessive retinal vascular tortuosity and an erythematous macular rash might be associated features of congenital sialidosis. PMID- 11195015 TI - Parental information needs in chronic renal failure and diabetes mellitus. AB - The information needs of parents of children with end stage renal failure (ESRF) or with insulin dependent diabetes mellitus (IDDM) were assessed by questionnaires over a 2-year period. Questionnaires were posted on seven occasions at 4-monthly intervals and were sent to both mothers and fathers. Most information needs were reported to be for detailed test results, for new information about the condition and about the child's future social development. Questions responsible for the three highest scores were concerned with the future: the child's fertility; their social, career and marriage prospects; and the hope for a new improved treatment. For the IDDM mothers, scores were significantly different depending on age of the child (P = 0.02). Change in treatment mode had no significant effect on the information needs of parents of children with ESRF (P = 0.81). Occupation was significantly associated with the mean general information needs scores for parents, with occupations of a lower socioeconomic status associated with higher information needs scores. There were no significant differences between the reported mean general information needs scores of parents of children with ESRF and of parents of children with IDDM (P = 0.69) or between mothers and fathers mean general information needs scores (P = 0.58). CONCLUSION: Multidisciplinary team members need to tailor information to the needs of the individual families and be sensitive to socioeconomic factors and communication issues. PMID- 11195016 TI - A major role of viruses in convulsive status epilepticus in children: a prospective study of 22 children. AB - A group of 22 previously healthy children with their first convulsive status epilepticus (SE), treated at Kuopio University Hospital, Finland, were prospectively studied. Eleven children had febrile and 11 afebrile SE. Polymerase chain reaction was used to detect specific DNA from CSF, enzyme immunoassays and immunofluorescence assays to detect specific antibodies in serum and CSF, viral cultures were obtained from CSF, throat and stool and antigen detection from throat specimens. Viral infection was identified in 10 of 11 children with febrile SE (91%) and in 7 of 11 with afebrile SE (64%). Human herpes virus 6 infection was identified in 12 children (55%), and in at least six of them the infection was primary. Single cases of human herpes virus 7, parainfluenza 3, adenovirus 1, echovirus 22, rota, influenza A and Mycoplasma pneumoniae infection were diagnosed. CONCLUSION: Viruses, human herpes virus 6 in particular, seem to be major associated factors in convulsive status epilepticus, both febrile and afebrile. Human herpes virus 7 and Mycoplasma pneumoniae are novel agents associated with status epilepticus. PMID- 11195018 TI - Diagnosis and treatment of the Pierre Robin sequence: results of a retrospective clinical study and review of the literature. AB - We performed a retrospective study of all children with Pierre Robin sequence (PRS), admitted to our hospital from 1981-1998 in order to evaluate diagnosis, treatment and prognosis. Patients were divided into two categories: isolated PRS (group 1) and PRS plus, i.e. PRS as part of a more complex syndrome (group 2). A total of 74 patients with PRS were found, 29 (39%) males and 45 (61%) females of whom 47 (63.5%) could be categorised as isolated PRS and 27 (36.8%) as PRS plus. The most frequent diagnoses in patients with PRS plus were Stickler syndrome and the velocardiofacial syndrome. Ophthalmological and fluorescent in situ hybridisation of chromosome 22 investigations should therefore be performed in all patients, as soon as the diagnosis of PRS is established. Some form of airway treatment was necessary in the majority of patients (52 of 74), most could be treated conservatively with prone/lateral positioning and close observation. Endotracheal intubation was necessary in one child from group 1 versus five from group 2. Tracheostomy was performed in three children from group 1 and two from group 2. Feeding problems occurred in about 25% of all PRS patients and stunted growth was seen especially in boys with isolated PRS before the age of 10 months. CONCLUSION: In our series, 33% of patients with Pierre Robin sequence plus had Stickler and velocardiofacial syndromes. Conservative airway management was a sufficient treatment for respiratory problems in the majority of patients. Feeding and growth need special attention in patients with Pierre Robin sequence. PMID- 11195017 TI - Gingival bleeding, epistaxis and haematoma three days after gastroenteritis: the haemorrhagic lupus anticoagulant syndrome. AB - A 3 year and 9 month-old girl presented with gingival bleeding, epistaxis, and multiple haematomas 3 days after an acute episode of gastroenteritis. Prothrombin time and activated partial thromboplastin time were prolonged with reduced clotting activity of factor II (< 10%), VIII (<1%), IX (3%), XII (10%) and evidence of a high titre inhibitor. Prothrombin (factor II) level was below the detection limit, both in a functional and immunological assay. It did not increase after administration of vitamin K or fresh frozen plasma. Further studies revealed presence of a strong lupus anticoagulant and a specific IgG antibody against prothrombin. Factor VIII antigen levels also were reduced (31%), but to a lesser extent than functionally determined factor VIII (<1%). Blood coagulation normalised following clinical recovery 6 weeks after admission. The pathophysiology of this acquired inhibitor phenomenon (accelerated clearance of complexes of clotting factors and phospholipids) is discussed. CONCLUSION: The haemorrhagic lupus anticoagulant syndrome (acquired hypoprothrombinaemia lupus anticoagulant syndrome) is a rare presentation of acquired bleeding diathesis in childhood. Since most cases in post-infectious children are asymptomatic, it might be underdiagnosed. In children with newly appearing bleeding symptoms or unclear prolonged prothrombin time or activated partial thromboplastin time, one has to consider this syndrome which could lead to relevant bleeding. PMID- 11195019 TI - Velofacial hypoplasia (Sedlackova syndrome): a variant of velocardiofacial (Shprintzen) syndrome and part of the phenotypical spectrum of del 22q11.2. AB - In 1955, a pattern of velar hypoplasia causing hypernasal speech and associated facial dysmorphism was observed in 26 children of Czech origin. Further cases with submucous cleft and/or cardiac anomalies were described. In 1978 velocardiofacial syndrome (VCFS) was reported, a condition very similar to velofacial hypoplasia (Sedlackova syndrome) apart from overt clefts instead of velar hypoplasia. In 1990 it was suggested that both syndromes might be variants of the same clinical entity. To test this hypothesis we performed fluorescence in situ hybridisation using the DiGeorge/VCFS region specific probe D22S75 on 20 patients originally classified as Sedlackova syndrome as well as molecular investigations for a subset of these patients. A 22q11.2 deletion was found in 16/20 patients. Thus, our results confirm the aforementioned hypothesis and expand the long list of clinical diagnoses associated with del 22q11.2. CONCLUSION: Velofacial hypoplasia (Sedlackova syndrome) and velocardiofacial (Shprintzen) syndrome have a corresponding phenotype and are both associated with del 22q11.2. PMID- 11195020 TI - Deficiency of CD4+ lymphocytes due to intestinal loss after Fontan procedure. PMID- 11195021 TI - Liver abnormality in Turner syndrome. PMID- 11195022 TI - The relatively short duration that a child retains a pacifier in the mouth during sleep: implications for sudden infant death syndrome. AB - The relatively short duration that a child retains a pacifier in the mouth during sleep has implications when the mechanism(s) of the apparent prophylaxis effect of pacifier use against sudden infant death syndrome are considered. PMID- 11195023 TI - Caudal blockade as alternative therapeutic approach in neonatal arterial thrombosis. AB - Considering the high frequency of bleeding complications following fibrinolytic treatment, caudal blockade could be used in association with lower doses of tissue plasminogen activator as a possible new therapeutic approach in management of arterial thrombosis in neonates. PMID- 11195024 TI - Improvement of neurological symptoms by enzyme replacement therapy for Gaucher disease type IIIb. AB - Enzyme replacement therapy might improve chronic liver dysfunction and contribute to the resolution of basal ganglia lesions in patients with type 3b Gaucher disease. PMID- 11195025 TI - Incontinentia pigmenti: a report of ten cases. AB - A multidisciplinary approach is necessary in the care of patients with incontentia pigmenti (Bloch-Sulzberger syndrome). PMID- 11195026 TI - Successful treatment of acquired undescended testes with human chorionic gonadotropin. AB - Human chorionic gonadotrophin therapy may have its place in the management of acquired undescended testes and surgery should be reserved for those who fail to respond to therapy. Further studies are necessary to evaluate these preliminary results. PMID- 11195027 TI - Partial agenesis of the corpus callosum with partial seizures and bilateral congenital lacrimal duct atresia. AB - Patients with partial agenesis of the corpus callosum can be readily detected by magnetic resonance imaging. PMID- 11195028 TI - Impaired autonomic control of the heart by SOX10 mutation. AB - The autonomic nervous system plays an important role in the generation of complex heart rate dynamics that enable an organism to adapt to stress. Little is known about genes influencing the development of this autonomic control of the heart. We suggest the SOX10 gene to be a candidate for this process. PMID- 11195029 TI - Premature adrenarche, increased growth velocity and accelerated bone age in male patients with Prader-Labhart-Willi syndrome. AB - Premature adrenarche/pubarche in male patients with Prader-Labhart-Willi syndrome may be associated with increased growth velocity and bone age acceleration. PMID- 11195030 TI - Lipopolysaccharide-induced nasal cytokine response: a dose-response evaluation. AB - Information on the dose-response relationship is a prerequisite to defining the non-response threshold of exposure. We investigated whether nasal lipopolysaccharide (LPS) challenges induce an inflammatory response in a dose dependent way. In three settings nasal lavage was performed before, and 20 min, 1, 6, 23, and 29 h after instillation of 0 microg, 10 microg, and 40 microg LPS for 10 s, in seven healthy subjects. Lavage fluids were analysed for concentrations of interleukin-6 (IL-6), IL-8, tumour necrosis factor-alpha (TNF alpha), histamine, and albumin. Symptoms were recorded by questionnaire and spirometric lung function was assessed after each lavage. The instillation of 40 microg LPS caused a small increase in nasal symptoms. TNF-alpha was below the detection limit (0.5 pg/ml) in most subjects and, like IL-8 and albumin, showed no relation to the LPS challenge. IL-6 increased over twofold with 10 microg LPS and over 13-fold with 40 microg LPS, with a peak at 6 h after LPS provocation, and the repeated design ANOVA was significant for dose and for time. Six hours after the 40 microg LPS challenge the histamine level significantly increased compared to the saline treatment. We conclude that short-lasting instillation of LPS causes a dose-dependent IL-6 release in the upper airways and minor nasal symptoms. PMID- 11195031 TI - Spontaneous compressive orbital emphysema of rhinogenic origin. AB - We report the case of a young patient who developed spontaneous compressive orbital emphysema after an attack of coughing. At admission the patient presented left proptosis, diplopia, vision impairment and headache. Computer tomography showed air in the lateral part of left orbit compressing the eyeball and the optic nerve medially. It also revealed a sphenoid bone dysplasia with hyperpneumatization of the left greater wing and with two dehiscences in its wall. It was very intriguing to discover that this sphenoid dysplasia and the flap of mucosa covering one dehiscence were causing a ball-valve effect, allowing air to enter but not leave the orbit. Endoscopic sinus surgery was successfully used to treat this case. PMID- 11195032 TI - Effect of irrigation of the nose with isotonic salt solution on adult patients with chronic paranasal sinus disease. AB - In a prospective, randomized, controlled, double-blind trial we compared the effectiveness of endonasal irrigations with Ems salt solution to that with sodium chloride solution in the treatment of adult patients with chronic paranasal sinus disease. Subjects (n = 40) were randomly allocated to treatment either with isotonic Ems salt solution or with isotonic sodium chloride solution. The treatment consisted of endonasal irrigation twice daily and additional nasal spray as required. Nasal endoscopy, plain radiography of the paranasal sinuses, olfactometry, anterior rhinomanometry, and a saccharin-clearance test were carried out on days 1 and 7. Patients recorded rating scales of general discomfort, nasal airway obstruction, agreeableness of the irrigation, duration of improved nasal resistance after each irrigation, and the amount of additional nasal spray in a diary. Nasal air flow was not improved significantly. Subjective complaints, endonasal endoscopy, and radiography results revealed a significant improvement in both groups (P = 0.0001). In comparison, the two groups were not significantly different in outcome. Endonasal irrigations with salt solutions are effective in the treatment of chronic sinusitis, and a significant difference between Ems salt and sodium chloride was not observed. PMID- 11195033 TI - Composite hyoid-sternohyoid interposition graft in the surgical treatment of laryngotracheal stenosis. AB - This article reports six patients with severe laryngotracheal stenosis. The causes of stenosis were tracheotomy (two cases); prolonged endotracheal intubation (one case); laryngeal trauma (two cases); and surgery with postoperative chemo- and radiotherapy, addressing a thyroid gland follicular adenocarcinoma (one case). Two patients were already tracheotomized. The main postoperative complication was necrosis of the graft in a female patient who had previously undergone treatment for thyroid follicular adenocarcinoma. All patients were decannulated 6 months postoperatively. Five patients were then regularly followed up, but we lost contact with one patient. Comparison between pre- and postoperative pulmonary function testing revealed an increased maximum inspiratory flow (Vi max50) in five cases between 0.57 l/s and 2.18 l/s. A helical scan with 3-dimensional reconstruction of the cervical area in four patients confirmed the presence and preservation of the hyoid bone graft. Four patients remained satisfied with their postoperative voice quality, one patient was dissatisfied, and one patient was not followed up. This technique is effective in adults with severe laryngotracheal stenosis, restricted to the first tracheal rings, providing one takes into consideration the main contraindications of the procedure: past history of radiotherapy and thyroid surgery. PMID- 11195034 TI - Primary carcinoma of the subglottic larynx. AB - Primary cancer of the subglottic region is very rare and delay in diagnosis often leads to a poor prognosis. We retrospectively reviewed 49 patients with primary cancer of the subglottic larynx observed from 1969 to 1993 in the ORL Clinic of the University of Florence. This number constitutes 1.6% of all laryngeal cancers observed during this period. Four (8.2%) patients were stage T1, 13 (26.5%) T2, 27 (55.1%) T3, and 5 (10.2%) T4. Forty-one patients were eligible for assessing the disease-free five-year survival rate, 17 of whom were treated with surgery alone, 6 with radiotherapy alone and 18 with combination therapy (surgery for the primary tumor and postoperative radiotherapy for cervical nodes). The five-year survival rate for the three treatment types was 47%, 0% and 83.3%, respectively. The overall survival rate was 56.1%. Combination therapy produced a significantly higher (P = 0.001) disease-free survival than surgery alone or radiotherapy alone. PMID- 11195035 TI - Fluorodeoxyglucose positron emission tomography, a new technique for increasing the detection rate of coincident thyroid cancer in head and neck oncology. AB - Clinically occult thyroid cancer is not uncommon and may occur in 1% to 10% of the population Since the first studies on the use of fluorodeoxyglucose positron emission tomography (FDG PET) in clinical oncology some reports have appeared on the detection of occult tumors using this imaging modality. According to these results, the number of patients with head and neck cancer and clinically occult coincident primary tumors at initial presentation may be expected to increase. In two of the four patients presented, the coincident tumor was detected with FDG PET. The possible role of this new imaging technique is discussed in correlation with treatment and clinical outcome. PMID- 11195036 TI - Schwannoma of the larynx: case report. AB - Neurogenous tumours of the larynx are extremely uncommon. We present a rare case of schwannoma of the larynx. Clinical findings are presented together with computed tomography (CT) and magnetic resonance images. The tumour was located in the right aryepiglottic fold of the larynx. CT showed a well defined and hypodense mass extending from the right aryepiglottic fold to the right vocal cord. The patient underwent an excision of the mass through a lateral thyrotomy and the tumour was completely removed. The diagnosis and treatment of this tumour are discussed. PMID- 11195037 TI - Merkel cell carcinoma of the auricle. AB - Merkel cell carcinoma is a rare, although increasingly recognized, malignant tumor of the skin. The most common site of occurrence is the head and neck (50%). Only five cases of this tumor on the auricle have been reported previously. We present a further such case. The incidence, clinical features, diagnosis, prognosis, and treatment of the Merkel cell carcinoma are discussed. PMID- 11195038 TI - Systematics in lymphatic tumor spread of carcinomas of the upper aerodigestive tract--a clinical study based on embryologic data. AB - BACKGROUND: The aim of this study was to assess the incidence and pattern of cervical lymph node (LN) metastases in carcinomas of the upper aerodigestive tract in relation to primary tumor (PT) invasion of the equivalents of pharyngeal arches (PhA) and occipital and cervical somites (OCS) in adults. METHODS: The pretherapeutic computed tomography scans and clinical findings in 729 patients with histologically proven carcinoma of the upper aerodigestive tract (112 nasopharyngeal, 289 oropharyngeal, 252 laryngo-hypopharyngeal, and 76 oral cavity carcinomas, with LN involvement in 70% of the total) were analyzed in relation to PT invasion of equivalents of PhA and OCS. Tumors were recorded according to the infiltration of these equivalents. The metastatic involvement of the different cervical LN groups was analyzed and correlated to the pattern of PT invasion of equivalents of PhA and OCS by the chi-square test. RESULTS: The findings show that the pattern of cervical LN involvement depends on the location and extension of the PT and its invasion of equivalents of the PhA and OCS. Jugular LN metastases were found in tumors invading the equivalents of PhA 2-6. Submandibular LN metastases were evident in tumors invading tissues arising from the first PhA and the tongue. Retropharyngeal, spinal accessory and transversa colli LN metastases were found in tumors invading tissues arising from OCS. The frequency of LN metastases in the different LN chains decreased in the cranio caudal direction. Each neck hemisphere showed separate lymphatic drainage. CONCLUSIONS: Analysis of PT extension in relation to PhA and OCS equivalents allows patterns of LN involvement to be predicted. PMID- 11195039 TI - Long-term results in the treatment of obstructive sleep apnea. AB - No recent update is available on long-term results of the various types of treatment of obstructive sleep apnea (OSA) which can help the physician in evaluating the individually tailored treatment for patients with OSA in the long term. We arbitrarily defined "long-term" results as those after at least 3 years and reviewed the literature from the past 25 years for reports on conservative, apparative, and surgical therapy of OSA in children and adults. Another inclusion criterion was that the diagnosis was also confirmed by polysomnography before treatment and at follow-up. Only relatively few long-term studies meeting the criteria of 'evidence based medicine' were found, comparing the findings of these was difficult or impossible due to varying criteria for success. Long-term data were available about the effect of weight reduction, nasal ventilation therapy, oral devices, tonsillectomy, uvulopalatopharyngoplasty, maxillomandibular advancement osteotomies, and tracheotomy. After approx. 25 years many treatment modalities in sleep medicine are still experimental concerning the long-term use for the individual. In particular, randomized controlled trials in surgery are lacking. Late results show that at least 50% of patients with OSA can be treated effectively by one or a combination of treatments. Nasal continuous positive airway pressure, tracheotomy, maxillomandibular advancement osteotomy, and tonsillectomy are the most effective treatments of OSA. PMID- 11195040 TI - Virtual endoscopy of the nasal cavity in comparison with fiberoptic endoscopy. AB - PURPOSE: To apply virtual-endoscopic mode to display the nasal cavity and to evaluate clinical application of virtual endoscopy in comparison with nasal fiberoptic endoscopy. MATERIALS AND METHODS: Eleven patients were examined by virtual endoscopy after axial spiral computed tomography (CT) scanning was performed. In addition, 9 out of these 11 patients underwent fiberoptic endoscopy. Spiral CT scanning was performed with 1-mm collimation, 0.5- to 1-mm increment, 25-250 mA s, and pitch 1-2. Virtual endoscopy was performed by Explorer software package. RESULTS: Virtual endoscopy could clearly demonstrate anatomic structures in the nasal cavity, septal deviation, stenosis and obstruction of the middle meatus, turbinate hyperplasia, and pathological masses larger than 3 mm in diameter. However, "false adhesions" may appear in virtual endoscopy. The main limitation of virtual endoscopy was the inability to evaluate mucosa and its surface. CONCLUSION: Virtual endoscopy of the nasal cavity is a new and noninvasive method. It can demonstrate normal and pathological structures in the nasal cavity. Its ability to visualize is comparable with fiberoptic endoscopy except for evaluating mucosal surface and secretions. In the future, this method will probably be a basic instrument of computer-assisted surgery in the midfacial region. PMID- 11195041 TI - Research on renal endothelin in proteinuric nephropathies dictates novel strategies to prevent progression. AB - Proteinuria is one of the major risk factors for renal disease progression in patients with chronic nephropathies. Studies in disease models have helped to delineate mechanisms leading to renal structural damage as a result of persistent dysfunction of the glomerular barrier to proteins, even when the primary immune or non-immune insult to the kidney has ceased. From these preclinical studies, a role for endothelin in proteinuric chronic renal diseases has been suggested, thus providing the rationale for novel therapeutic approaches with endothelin receptor antagonists to maximize renoprotection so far achieved with blockade of the renin-angiotensin system by angiotensin-converting enzyme inhibition or angiotensin II receptor antagonism. Trials are needed to explore this potential area of clinical interest. PMID- 11195042 TI - Aldosterone in renal disease. AB - Blockade of the renin-angiotensin-aldosterone system has proved effective in retarding the progression of renal disease in the remnant kidney model, as well as other experimental diseases, and most importantly, in a range of progressive human renal diseases. Attention has focused on the role of angiotensin II in propagating progression both by its hemodynamic and non-hemodynamic actions. Recent evidence, predominantly in the remnant kidney model, indicates that the drugs used to block this hormone system, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, also lower aldosterone levels. Aldosterone as well as angiotensin II thus appears to be instrumental in sustaining the hypertension and fibroproliferative destruction of the residual kidney. PMID- 11195043 TI - Angiotensin II type 1 receptor gene polymorphisms in humans: physiology and pathophysiology of the genotypes. AB - Many studies have attempted to relate genetic variants of components of the renin angiotensin system to complex diseases such as essential hypertension, cardiovascular disease and progressive renal failure. The angiotensin II type 1 receptor (AT1R) gene is an important example of this approach. Many polymorphisms of the AT1R gene have been identified, but the A1166-->C polymorphism has been the most extensively studied. The physiological significance of this polymorphism is uncertain because of its location in the 3'-untranslated region of the gene. The present review summarizes association studies of the AT1R gene, focusing on clinical end-points and physiological responses. PMID- 11195044 TI - Bibliography. Current world literature. Hormones, autacoids, neurotransmitters and growth factors. PMID- 11195046 TI - Bibliography. Current world literature. Circulation and hemodynamics. PMID- 11195045 TI - Growing kidneys. AB - The number of kidney transplantations performed per year is restricted by the limited availability of donor organs. One possible solution to this shortage is the use of renal xenografts. However, the transplantation of xenografts is complicated by hyperacute and acute rejection. A second possible solution is to 'grow a kidney' from a transplanted renal anlage. It has been postulated that the host immune response might be attenuated after the transplantation of such an anlage (metanephros) instead of a developed kidney. Transplanted metanephroi become chimeric organs in that their blood supply originates, at least partly, from the host. It is possible to transplant a developing metanephros, without the use of immunosuppression, from one rat to another. Transplanted metanephroi grow, differentiate, become vascularized, and function in host rats. 'Growing kidneys' via the transplantation of metanephroi may hold promise as a novel therapeutic approach to the treatment of chronic renal failure. PMID- 11195047 TI - CD2-associated protein and the kidney. AB - During the past 3 years there have been significant advances in our understanding of the biology of the glomerular podocyte. In particular, two proteins, CD2 associated protein and nephrin, have been identified as critical podocyte proteins that are both required for normal glomerular filtration. In addition to supporting the idea that the slit diaphragm plays a crucial role in glomerular function, these results suggest novel insights into the pathogenesis of glomerular diseases. The present review addresses these recent advances and discusses the implications of the findings. PMID- 11195048 TI - Current advances in molecular genetics of autosomal-dominant polycystic kidney disease. AB - Autosomal-dominant polycystic kidney disease results from at least two causal genes, PKD1 and PKD2. The identical clinical phenotype in human patients and targeted Pkd1 and Pkd2 mutant mouse models provides evidence that both gene products act in the same pathogenic pathway. The discovery of direct PKD1 and PKD2 interactions implies that both gene products, polycystin-1 and polycystin-2, play a functional role in the same molecular complex. The spectrum of germ-line mutations in both genes and the somatic mutations identified from individual PKD1 or PKD2 cysts indicate that loss of function of either PKD1 or PKD2 is the mechanism of cystogenesis in autosomal-dominant polycystic kidney disease. A novel mouse model, Pkd2WS25/-, has proved that loss of heterozygosity is the molecular mechanism of autosomal-dominant polycystic kidney disease. Recently, studies on the expression patterns of PKD1 and PKD2 in humans or mice indicate that polycystin 1 and polycystin 2 seem to have their own respective functional roles, even though most of the functions of these polycystins are parallel during human and mouse development. Pkd2-deficient mice have cardiac septum defects, but Pkd1 knockout mice do not have this phenotype. On the other hand, Pkd2 has a very low level of expression in the central nervous system when compared with Pkd1. In addition, the level of expression of Pkd1 is increased during mesenchymal condensation, whereas Pkd2 expression is unchanged. Preliminary data have shown that the PKD1/PKD2 compound trans-heterozygous has a more severe cystic phenotype in the kidney than that of an age-matched heterozygous type 1 or type 2 of autosomal-dominant polycystic kidney disease alone. This finding suggests that PKD1 may be a modifier of disease severity for PKD2, and vice versa. The characteristics of the contiguous PKD1/TSC2 syndrome phenotypes and the data from Krd mice imply that TSC2 and PAX2 may also serve as potential modifiers for the disease severity of autosomal-dominant polycystic kidney disease. PMID- 11195049 TI - The roles of cubilin and megalin, two multiligand receptors, in proximal tubule function: possible implication in the progression of renal disease. AB - Proteins that have not been retained by the glomerulus are reabsorbed in the proximal tubule by endocytosis, a process that involves binding at the apical pole of the tubule cell, vesicular internalization and subsequent lysosomal degradation. Data presented in this review indicate that the initial recognition step involves two high molecular weight proteins, megalin and cubilin, which have multiligand properties and can therefore account for the wide variety of proteins reabsorbed. Given the potential importance of transepithelial protein traffic in the induction of interstitial fibrosis, the identification of these receptors may have implications in the progression of acute or chronic renal disease and may provide a target for therapeutic intervention. PMID- 11195051 TI - Cytokines and hormones with anti-inflammatory effects: new tools for therapeutic intervention. AB - The inflammation that is involved in the development of glomerulonephritis is tightly regulated by the expression of anti-inflammatory factors. These include circulating hormones, such as glucocorticoids, and mediators that are produced by intrinsic cells and infiltrating leucocytes. The present review focuses on these anti-inflammatory factors, summarizing in particular their activities in existing models of glomerulonephritis. In addition, experimental evidence is presented that anti-inflammatory mediators are able to increase glucocorticoid binding or signalling in target cells. These data help to explain the in-vivo efficacy of anti-inflammatory mediators, and offer a promising new avenue for therapeutic intervention. PMID- 11195050 TI - Sodium reabsorption in aldosterone-sensitive distal nephron: news and contributions from genetically engineered animals. AB - The precise adaptation of renal sodium excretion to systemic needs is to a large extent achieved by the regulation of sodium re-absorption in the aldosterone sensitive distal nephron. Transcellular sodium re-absorption by the segment specific cells of the aldosterone-sensitive distal nephron (often called principal cells) is mainly controlled at the level of the expression and activity levels of the epithelial sodium channel, the apical amiloride-sensitive sodium influx pathway. Recent investigations have identified the first early aldosterone induced proteins that act on epithelial sodium channel function in expression systems. Indirect evidence suggests that one of these aldosterone-induced proteins, the serum- and glucocorticoid-inducible protein kinase SGK1, plays a central integratory role in the control of epithelial sodium channel surface expression and activity, also in the mammalian kidney. Gene-modified animals lacking epithelial sodium channel subunits or expressing mutant subunits have substantiated the central role of the epithelial sodium channel in sodium re absorption and blood pressure control, as well as for neonatal lung liquid clearance. Mice overexpressing or lacking specific hormones or their receptors have been used to study their role in sodium transport regulation, but the study of mouse physiology appears to lag behind the generation of gene-modified mice. Nonetheless, these new animal models have had a strong impact on research, by stimulating the integration of knowledge and techniques learned from reductionistic molecular approaches into tissue and animal studies, thus breaking down barriers and stimulating collaborations. PMID- 11195052 TI - Cytokine cross-talk between tubular epithelial cells and interstitial immunocompetent cells. AB - Immunostaining of renal biopsies of patients with interstitial rejection of allografts or other forms of interstitial inflammation has demonstrated the presence of activated T cells and monocytes/macrophages in the tubulointerstitial area. Cytokines that are produced by infiltrating cells are capable of activating tubular epithelial cells. In turn tubular epithelial cells can produce a wide variety of inflammatory mediators, including chemokines, which further regulate cellular influx. Interfering in this cross-talk between tubular epithelial cells and infiltrating cells might provide new options for therapeutic intervention. PMID- 11195053 TI - Implications from the Heart Outcomes Prevention Evaluation Study. PMID- 11195054 TI - Considerations for the evaluation of renal function in genetically engineered mice. AB - Transgenic and gene-targeting techniques have opened a new era of physiologic investigation: the field of functional genomics. The nearly exclusive use of the mouse in this discipline has necessitated the development and adaptation of sophisticated techniques for evaluating murine physiology at the cellular, tissue, organ and whole animal levels. Although many of the methodologies for exploring cardiorenal function have been successfully adapted from their use in the rat, there are important limitations and considerations that must be recognized when applying them in the mouse. Investigators have been successful in measuring a wide variety of functional variables at the whole kidney and even single nephron levels. Reviewed here are recent advances in the measurement of blood pressure, renal blood flow, whole kidney electrolyte excretion and clearance rates, single-nephron glomerular filtration rate and transport, and tubuloglomerular feedback. PMID- 11195055 TI - Do matrix metalloproteinases MMP-2 and MMP-9 (gelatinases) play a role in renal development, physiology and glomerular diseases? AB - Metalloproteinases MMP-2 and MMP-9 (also called gelatinases) are involved in cell invasion and in embryonic development and organogenesis. A growing number of reports suggest that MMP-2 and MMP-9 play some role in renal development, renal tubule physiology and glomerular pathophysiology. This editorial will focus on recent controversial data, especially those obtained from studies on MMP-9 deficient mice, which shed new light on the functions of gelatinases in normal and diseased kidneys. PMID- 11195056 TI - Molecular genetics of essential hypertension: recent results and emerging strategies. AB - Efforts to identify hypertension-predisposition genetic loci have focused largely on candidate gene strategies, in which specific candidates have been tested for linkage and association with blood pressure or the diagnosis of hypertension. A variety of candidate genes have been investigated, including loci involving the renin-angiotensin-aldosterone system, sodium epithelial channel, catecholaminergic/adrenergic function, renal kallikrein system, alpha-adducin, and others involving lipoprotein metabolism, hormone receptors, and growth factors. These studies, and more recently, several genome-wide scans, have yielded highly promising results suggesting a number of potential candidate genes and genomic regions that may contribute to blood pressure variation. The results also point to the need for more robust phenotypes that are intermediate in the pathogenetic development of high blood pressure. Additional methods and strategies for improving genetic studies of human hypertension include comparative genomics, in which results from animal studies are used to target potential blood pressure loci, the use of newly developed quantitative tests of linkage and association, comprehensive single-nucleotide polymorphism discovery in candidate loci, and the use of single-nucleotide polymorphisms in cladistic/haplotype analyses and genome-wide searches. PMID- 11195057 TI - Cytochrome P450 metabolites of arachidonic acid in the control of renal function. AB - Recent studies indicate that arachidonic acid is primarily metabolized by cytochrome P450 enzymes of the 4A and 2C families in the kidney to 20 hydroxyeicosatetraenoic acid (HETE), epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids. These compounds play central roles in the regulation of renal tubular and vascular function. 20-HETE is produced by renal vascular smooth muscle (VSM) cells and is a potent constrictor that depolarizes VSM cells by blocking the calcium-activated potassium channel. Inhibition of the formation of 20-HETE blocks the myogenic response of isolated renal arterioles in vitro, and autoregulation of renal blood flow and tubuloglomerular feedback responses in vivo. EETs are products formed in the endothelium and are potent dilators that activate the calcium-activated potassium channel in renal VSM. Endothelial-dependent vasodilators stimulate the release of EETs, and these compounds appear to serve as an endothelial-derived hyperpolarizing factor. EETs and 20-HETE are produced in the proximal tubule. There, they regulate sodium/potassium-ATPase activity and serve as second messengers for the natriuretic effects of dopamine, parathyroid hormone and angiotensin II. 20-HETE is also produced in the thick ascending loop of Henle. It regulates sodium potassium-chloride transport in this nephron segment. The renal production of cytochrome P450 metabolites of arachidonic acid is altered in hypertension, diabetes, toxemia of pregnancy, and hepatorenal syndrome. Given the importance of cytochrome P450 metabolites of arachidonic acid in the control of renal function, it is likely that changes in this system contribute to the abnormalities in renal function that are associated with many of these conditions. PMID- 11195058 TI - Cyclooxygenase 2 and the kidney. AB - Cyclooxygenase metabolizes arachidonic acid to a family of bioactive fatty acids designated prostaglandins. Two isoforms of cyclooxygenase exist, designated COX1 and COX2. These isoforms are expressed in distinct but important areas of the kidney. COX1 predominates in vascular smooth muscle and collecting ducts, whereas COX2 predominates in the macula densa and nearby cells in the cortical thick ascending limb. COX2 is also highly expressed in medullary interstitial cells. Whereas COX1 expression does not exhibit dynamic regulation, COX2 expression is subject to regulation by several environmental conditions, including salt intake, water intake, medullary tonicity, growth factors, cytokines, and adrenal steroids. Recently, COX2-selective non-steroidal anti-inflammatory drugs have become widely available. Many of the renal effects of non-selective non-steroidal anti-inflammatory drugs (including sodium retention, decreased glomerular filtration rate, and effects on renin-angiotensin levels) appear to be mediated by the inhibition of COX2 rather than COX1. Therefore, in contrast to the gastrointestinal-sparing effects of COX2-selective non-steroidal anti inflammatory drugs, when considering the kidney, the same caution must be applied when using COX2-selective inhibitors as has been used with traditional non selective non-steroidal anti-inflammatory drugs. PMID- 11195059 TI - Angiotensin type 2 receptors: potential importance in the regulation of blood pressure. AB - The angiotensin type 2 receptor is one of two major angiotensin II receptors that has been identified, cloned and sequenced. The other major receptor, the angiotensin type 1 receptor, is thought to mediate most of the biological responses to the peptide. The angiotensin type 2 receptor is expressed heavily in fetal tissues, but only at a low level in the adult. Documented angiotensin type 2 receptor expression sites in the adult include kidney, heart and mesenteric blood vessels. The function of the angiotensin type 2 receptor is just beginning to be explored. Most of the evidence suggests that the angiotensin type 2 receptor mediates a vasodilator signalling cascade that includes bradykinin, nitric oxide and cyclic guanosine 5-monophosphate. At least some of the beneficial actions of angiotensin type 1 receptor blockade, such as hypotension, are mediated by stimulation of the angiotensin type 2 receptor. Several recent papers suggest that angiotensin type 2 receptors, presumably located in systemic blood vessels, mediate vasodilation and hypotension. The angiotensin type 2 receptor may be a new therapeutic target and candidate gene for the pathophysiology of hypertension. PMID- 11195060 TI - [Strategies for preoperative therapy of locoregional cancers: an opportunity for expanding current concepts]. PMID- 11195061 TI - [Molecular markers as basis for chemotherapy?]. AB - Although a majority of cancer patients show no response or minimal response to any given chemotherapy, all patients are nevertheless placed on standard therapy regimens because there has been no way to identify beforehand those patients who are destined not to respond. Determining the biochemical factors relevant to drug response in each patient's tumor cells prior to treatment should allow optimal therapy to be selected for each patient on a rational basis. In this paper, we summarize studies aimed at determining whether analysis of the quantitative expression levels of genes or proteins involved in cancer drug activity in clinical specimens of tumor tissue could predict the effect of the drug on a tumor. This hypothesis has been tested mostly in 5-fluorouracil (5-FU)-based regimens in colorectal cancer. In the case of 5-FU, the quantitative expression levels of thymidylate synthase, thymidine phosphorylase, and dihydropyrimidine dehydrogenase were found to be associated with tumor response. Using all three of these markers together resulted in very effective identification of responding patients. The salient results of these studies were that, using the PCR enhanced by newly developed methodology, gene expressions can be identified and measured in pretreatment biopsies that are quantitatively associated with either response or non-response to drugs that are used in treating colorectal cancer. PMID- 11195062 TI - [Confirmed preoperative therapy of rectal carcinoma]. AB - Optimized surgical management is the most important factor influencing prognosis of patients suffering for rectal carcinoma. Oncologically radical surgical procedures with the intent of histologically complete resection should be performed, including excision of the tumour in total with sufficient margins in the oral and aboral directions. Total excision of the mesorectal tissue, at least in low-lying rectal tumours, is strongly recommended. Several retro- and prospective studies show that the surgeon him- or herself, using these adequate techniques, is the most important, statistically significant independent prognostic factor in patients with rectal carcinoma. In addition, adjuvant radiochemotherapy, given before or after surgery, decreases the local failure rates of high-risk patients (UICC stages II and III). Such radiochemotherapy is, to the great variety of different local failure rates in different surgical departments mandatory as recommended by the consensus conference of the German Cancer Society in July 1999. New and improved radiation techniques (conformal radiotherapy, intraoperative radiotherapy) could significantly decrease therapy related toxicity, and innovative schedules (continuous low-dose 5-FU) may show increased therapeutic benefit of adjuvant treatment. Combined radiochemotherapy prior to surgery seems to increase the rate of sphincter-preserving procedures in low-lying rectal cancer. Definitive results and a clear advantage of pre- over postoperative radiochemotherapy (currently being tested in a German multicenter study) are still pending. PMID- 11195063 TI - [New therapy approaches in tumors of the upper gastrointestinal tract (esophagus, stomach)]. AB - Despite numerous phase-II and phase-III studies investigating neoadjuvant treatment in esophageal and gastric cancer, the value of multimodal therapy in these tumors is not clearly defined yet. One reason are the different study entry criteria and different staging modalities in the investigations published so far. Concerning esophageal cancer, neoadjuvant chemotherapy does not yet have a definite role after several phase-III studies. It may be that this treatment should only be inaugurated in innovative protocols. Furthermore, in esophageal cancer it is proven that chemoradiation is superior to radiation alone in the neoadjuvant setting. Following neoadjuvant chemoradiation, there is a distinct trend in favor of multimodal therapy. In the case of locally advanced squamous cell carcinoma of the esophagus, neoadjuvant chemoradiation offers 30%-60% of the patients the possibility for a complete resection (UICC-R0); however, this is accompanied by increased postoperative morbidity and mortality. In gastric cancer, neoadjuvant chemotherapy is still an experimental approach. Intraperitoneal chemotherapy has failed to show any benefit in Western trials. Clinically related research is concentrating on the problem of distinguishing responder from non-responder at the beginning of the therapy. First results indicate that with molecular markers, response might be predicted before therapy. Using 18-FDG PET, it could be possible that the response can be recognized after only 1 week of treatment, opening the door to early response evaluation. New therapeutics like monoclonal antibodies for adjuvant therapy, which is again under discussion in gastric cancer, are only in phase-I studies. PMID- 11195064 TI - [Evaluation of neoadjuvant therapy in breast carcinoma]. AB - For 20 years preoperative chemotherapy has been the treatment of choice in inflammatory breast cancer. Adjuvant chemotherapy does not show any advantages over neoadjuvant systemic chemotherapy in terms of survival of patients with breast cancer. Reduction of the size of the tumor enables the surgeon to perform more breast-conserving surgery, but the long-term results for breast tumor to recur in these patients are not yet available. At our hospital, a tumor larger than 30 mm is an indication for mastectomy. In general, only 20.6% of all patients are suitable for neoadjuvant chemotherapy. Patients with lobular carcinoma or with tumors with an extensive ductal carcinoma in situ part will not benefit from such therapy. Tumor remission following neoadjuvant chemotherapy is of prognostic relevance. The rapid therapeutic effect of neoadjuvant therapy allows short-term evaluation of this treatment. PMID- 11195065 TI - [Differential indications for induction therapy of non-small-cell lung tumors]. AB - Induction chemotherapy and induction chemo-radiotherapy have shown their efficiency and feasibility in many phase-II studies and have profen superior to operation alone in stage IIIa of NSCLC in several phase-III studies. Therefore it is justified to recommend this multimodal therapy in stage IIIa N2 disease within clinical studies. However, it is currently not justified to present this multimodal treatment modality as a generally agreed standard. PMID- 11195066 TI - [Minimally invasive parathyroidectomy with local anesthesia in conjunction with ultrasonography, sestamibi scintigraphy and intraoperative parathyroid hormone measurement]. AB - INTRODUCTION: The standard procedure in patients with primary hyperparathyroidism (pHPT) includes cervical exploration and identification of all four enlarged parathyroid glands. New localization techniques, i.e., ultrasonography associated with color duplex sonography, 99mTc-sestamibi scintigraphy and the possibility of intraoperative parathormone (iPTH) measurement permit minimally invasive parathyroidectomy (MIP). Three different methods have been established: minimally invasive open parathyroidectomy, endoscopic parathyroidectomy and video-assisted parathyroidectomy. We present our experience with open MIP with the patient under local anesthesia (LA). METHODS: In 25 patients with pHPT the operation was started under local anesthesia. Preoperatively, ultrasonography and sestamibi scintigraphy were performed in each patient. iPTH measurement was carried out intraoperatively. RESULTS: In 23 patients (92%) the operation was done successfully in LA. There were no postoperative complications. During follow-up none of the patients developed hypercalcemia again. CONCLUSION: MIP in connection with ultrasonography, sestamibi scintigraphy and intraoperative PTH measurement offers a promising treatment for patients with pHPT. PMID- 11195067 TI - [Use of the heart-lung machine in extra-cardial carcinoma surgery]. AB - The employment of the heart-lung machine to assisting the circulatory system for the resection of extracardial tumors is increasing because of their location, growth and infiltration. We report on three patients in whom the resection of the tumor was only possible with extracorporeal circulation (ECC). In the first patient sarcoma of the pulmonary artery and valve was resected under ECC. Artery and valve were replaced with a cryo-preserved valved bifurcation homograft. In the other patients ECC was used on the basis of tumorinfiltration of the inferior vena cava and tumor embolus of the pulmonary artery in a case of primary renal cell carcinoma, and tumor infiltration of the superior vena cava and right atrium in a case of follicular thyroid carcinoma. All patients had a good postoperative course and excellent long term survival. PMID- 11195068 TI - [Paraneoplastic hypoglycemia in localized fibrous tumors of the pleura]. AB - Localized fibrous tumor of the pleura is a rare, slowly growing, benign tumor which originates from the submesothelial stem cells of the pleura visceralis. Most of these tumors clinically behave asymptomatically, although tumor associated hypoglycemia occurs in a few cases and can lead to hypoglycemic coma. Laboratory investigations show significant elevation of paraneoplastic IGF-II with a 2-3 times higher effect on the blood glucose level than insulin. Further, one finds reduced synthesis of IGFBP-3, which inhibits the action of IGF-II by inducing a complex with the paraneoplastic protein. As treatment, surgical resection of the tumor is recommended. We report on the case of a 72-year-old man with diabetes mellitus type II, who complained of recurrent hypoglycemic episodes. Diagnostic evaluation showed a fibrous tumor attached to the right diaphragm. After surgical treatment the hypoglycemic episodes disappeared. PMID- 11195069 TI - [Parathyroid gland carcinoma with postoperative encephalopathy]. AB - We present a 78-year-old patient who suffered from symptomatic transitory psychotic syndrome after laparotomy. Persisting somnolence appeared with cardiopulmonary decompensation and gastrointestinal atony. Due to prolonged hypercalcemia primary hyperparathyreoidism was diagnosed. Resection of a large carcinoma of the parathyroids led to continuous clinical improvement. PMID- 11195070 TI - [Possible variations of free autogenous jejunum transplantation for differential reconstruction of the oropharynx]. AB - INTRODUCTION: Resections of extensive tumours, recurrences and radiodermatitides at the neck cause complex defects. Free bowel transplantation enables one-stage reconstruction. PATIENTS AND METHODS: In 35 out of 57 interdisciplinarily treated patients, small-bowel transplantation was performed for reconstruction. Thirty patients received cylinder grafts, five jejunal patch plastics. In four patients neoglottis formations according to Ehrenberger were performed. To cover soft tissue defects, two patients received scapular free flaps, eight patients a jejunal segment, incised at the anti-mesenteric side, the mucosa stripped and covered by a split skin graft. RESULTS AND CONCLUSIONS: Thirty-four grafts were viable. One patient received a successful re-transplantation. One postoperative fistula at the hypo-pharyngojejunostomy was closed by a separated jejunal segment which was primarily used as monitor, two others by pectoral flaps. Separation of a jejunal graft into two or three segments enables restoration of swallowing, voice and covering soft tissue in a one-stage procedure. The whole reconstruction necessitates only one arterial and one venous microanastomosis at the neck. PMID- 11195071 TI - [Long-term follow up of bile duct injury by laparoscopic cholecystectomy and reconstruction with jejunum interposition]. AB - The follow-up of patients with severe bile duct lesions after laparoscopic cholecystectomy often shows secondary complications. We report on a female patient suffering from long-lasting complications after bile duct injury and early reconstruction by end-to-end anastomosis via a T-tube drainage. More than 5 years later and after multiple dilatation and stenting of the bile duct stenosis the patient was treated with an expanding metal stent. The severe cholangitis persisted. So the patient was operated on: bile duct and connected stent were resected. The reconstruction was performed with an isoperistaltic jejunal conduit. More than 24 months later the patient is healthy and at work again. PMID- 11195072 TI - [Endoscopic excision of extra-adrenal pheochromocytomas (paragangliomas)]. AB - We describe the successful endoscopic removal of six extra-adrenal pheochromocytomas in three patients. One neoplasia was located retrocavally, two between the aorta and vena cava, two by the para-aortal, and one by the parailiacal. The tumors were removed by the posterior retroperitoneoscopic or by the anterior laparoscopic approach, respectively. The intraoperative and postoperative courses were uneventful. PMID- 11195073 TI - [Extramedullary hematopoiesis as differential mediastinal space-occupying lesion diagnosis]. AB - Intrathoracic extramedullary hematopoiesis is a rare disease in the differential diagnosis of mediastinal masses. It is suggested that asymptomatic masses should not be treated. A correct diagnosis can thus help to avoid an operation. The aim of this case report is to draw attention to this phenomenon as a cause of mediastinal masses and to provide information about diagnostic facilities available. We report the case of a 53-year-old male patient with hereditary spherocytosis as well as the case of a 59-year-old male patient with pyruvate kinase deficiency who showed intrathoracic paravertebral masses, that were identified in the first case by video-assisted thoracoscopic intervention (VATS) and in the second case by thoracotomy as a region of extramedullary hematopoiesis. PMID- 11195074 TI - [Squamous epithelial carcinoma in a Zenker diverticulum]. AB - Zenker's diverticulum is a common anomaly in the elderly patient. Carcinoma in such a diverticulum is a rare but recognized complication of a posterior pharyngeal pulsion diverticulum. We present a case of a 67-year-old patient with a long-standing symptomatic Zenker's diverticulum. The diagnosis of the neoplasm was only achieved intraoperatively. The patient underwent a proximal esophageal resection with lymphadenectomy. Reconstruction was done with a microvascular free jejunal transplant. The postoperative course was uneventful. Wide oncologic surgical resection is the therapy of choice in cases of carcinoma in a Zenker's diverticulum. PMID- 11195075 TI - [Laparoscopic cholecystectomy in isolated gallbladder metastasis of malignant melanoma]. AB - Metastasized malignant melanomas can affect all organs of the human body. However, isolated metastatic spreading into the gallbladder is rare. We treated two asymptomatic patients who had undergone primary curative resection of a melanoma. Gallbladder structures suggesting the presence of tumors were noticed in the follow-up investigations. The two patients underwent laparoscopic cholecystectomy to clarify their pathological relevance. Histologically, the tumor was a metastasis of the malignant melanoma in each case. Surgery is indicated in stage IV in isolated metastatic spreading to the gallbladder in order to avoid symptoms or tumor complications. Since the vast majority of melanoma metastases of the gallbladder are located intraluminally and lymphadenectomy in the region of the hepatoduodenal ligament does not appear to be appropriate, the operation should be carried out laparoscopically. The value of postadjuvant chemoimmunotherapy after metastasis resection is being investigated in numerous studies at present. PMID- 11195076 TI - [Internet presence of surgical clinics in Germany. Current data and future prospects]. AB - INTRODUCTION: The aim of this study was to obtain an overview of the use of the Internet by surgical departments in Germany as a presentation platform and information resource for their patients. METHODS: After a randomizing a total of 1,760 surgical departments in Germany, 200 were chosen and asked about their Internet use. RESULTS: Most of the questionnaires (81.5%) were received and analyzed; 32.5% of the German surgical departments are represented on the Internet; 81.4% of the clinics without a homepage are planning to have one in the future. The hospitals represent themselves on average on two HTML documents. CONCLUSION: Approximately a third of the German surgical departments currently give information over the Internet with a wide and heterogeneous spectrum. In the near future approx. 80% of the German surgical departments will have online presence. Therefore, the increasing demand for medical information by the patients will be fulfilled. The professionalism and effectiveness of the home pages can be increased through registration with many search engines and the use of e-mail. PMID- 11195077 TI - [Comment on Ch. Konh"auser et a.: Operation method determines recurrence incidence of colorectal carcinomas]. PMID- 11195078 TI - [Comment on P. Fricke et al.: Multiple metachronous metastases of renal cell carcinoma in the pancreas]. PMID- 11195079 TI - [Comment on B. J. Leibl et al.: Laparoscopic inguinal hernia therapy as training operation]. PMID- 11195081 TI - [Surgical endoscopy: as won, so lost?]. PMID- 11195080 TI - [Benign diseases of the gallbladder and bile ducts]. PMID- 11195083 TI - Urine stone formation during treatment with zonisamide. PMID- 11195082 TI - [Is there a "collective malpractice" for physicians?]. PMID- 11195084 TI - Periventricular leukomalacia and tumor necrosis factor. PMID- 11195085 TI - cDermo-1 expression indicates a role in avian skin development. AB - Basic helix-loop-helix (bHLH) transcription factors have been shown to be important regulatory proteins for tissue determination and differentiation. We cloned the chicken homologue of the gene of the murine Twist-related bHLH protein Dermo-1, which we named cDermo-1, and analyzed its sequence and embryonic expression. Our sequence data suggest a decisive role of Dermo-1 proteins in the evolution of amniote skin. We present a detailed analysis of cDermo-1 expression during avian embryonic development. cDermo-1 is first expressed in a variety of mesodermal tissues of the chick embryo including the limb buds, but later becomes restricted to the subectodermal mesenchyme of the integument and the developing feather buds, indicating a role of cDermo-1 during avian skin and feather development. PMID- 11195086 TI - Okadaic acid-induced inhibition of protein phosphatase 2A enhances chondrogenesis in chicken limb bud micromass cell cultures. AB - The role of major cellular serine/threonine-specific protein phosphatases, protein phosphatase 1 and 2A, was investigated during chicken cartilage differentiation under in vitro conditions. Activity of protein phosphatase 2A decreased parallel to differentiation of chondrogenic cells, whereas activity of protein phosphatase 1 remained unchanged as assayed in the supernatants of the homogenised chicken limb bud micromass cell cultures. When okadaic acid, a potent inhibitor of protein phosphatase 1 and 2A was applied in 20 nM concentration for 4 h during the second and third culturing days, it significantly increased the size of metachromatic cartilage areas measured in 6-day-old colonies. Following okadaic acid treatments, a significant inhibition in the activity of protein phosphatase 2A was found, while the activity of protein phosphatase 1 was unaffected as measured an days 2 and 3. TRITC-phalloidin labelling demonstrated that okadaic acid disorganised actin filaments and induced rounding of chondrogenic cells. This deterioration of actin filaments was reversible. Electron microscopy and biochemical analysis of colonies revealed that the ultrastructure and major components of cartilage matrix remained unchanged under the effect of okadaic acid. Okadaic acid-treatment applied to cultures containing predominantly differentiated chondrocytes (after day 4) did not influence the cartilage formation. 3H-thymidine and bromodeoxyuridine incorporation-assays demonstrated enhanced cell proliferation in the okadaic acid-treated colonies compared to that of the untreated ones. Our results indicate, for the first time, that protein phosphatase 2A is involved in the regulation of chondrogenesis. Inhibition of protein phosphatase 2A with okadaic acid may result in increased chondrogenesis via modulation of proliferation and cytoskeletal organisation, as well as via alteration of protein kinase A-signaling pathway of the chondrogenic cells. PMID- 11195087 TI - Ingrowth of sympathetic innervation occurs concomitantly with a decrease of ANP in the growing rat cardiac ventricles. AB - The relationship between the immunohistochemical expression of atrial natriuretic peptide and the occurrence of sympathetic nerve fibres, as visualized by staining for tyrosine hydroxylase, in the growing rat heart was evaluated. Rats were investigated at four different stages from birth to 21 days postnatally. The effects of chemical destruction of sympathetic nerve terminals in neonatal rats on the cardiac atrial natriuretic peptide content were furthermore examined by use of radioimmunoassay. There was in principle a reciprocal pattern of immunoreaction for atrial natriuretic peptide and tyrosine hydroxylase positive innervation in the ventricular myocardium, atrial natriuretic peptide reaction becoming less and less pronounced with the ingrowth of innervation positive for tyrosine hydroxylase. Furthermore, in the peripheral Purkinje fibre network, there was a marked atrial natriuretic peptide immunoexpression and scarce or no nerve fibres throughout the examination period. The radioimmunoassay measurements showed that chemical sympathectomy lead to elevated cardiac levels of atrial natriuretic peptide. The study shows that sympathetic innervation grows into the ventricular parts concomitantly with the occurrence of a decline in atrial natriuretic peptide expression during development of the heart. Furthermore, it is shown that a reversion of the in growth of sympathetic innervation by destruction of cardiac sympathetic nerves at an early stage leads to increased levels of atrial natriuretic peptide in the heart. The results give new evidence to the phenomenon that the atrial natriuretic peptide levels in the ventricular myocardium and the peripheral parts of the conduction system are under influence of the presence of sympathetic innervation. PMID- 11195088 TI - Wisteria floribunda agglutinin labeling patterns in the human cortex: a tool for revealing areal borders and subdivisions in parallel with immunocytochemistry. AB - Wisteria floribunda agglutinin (WFA) is a lectin that labels selectively N acetylgalactosamines beta 1 (GalNAc beta 1-3 Gal) residues of glycoproteins within the extracellular matrix of the neurons, and has been identified as a specific marker for functionally different cortical areas of the rodent brain. Here we report that WFA-binding sites can be used for the characterization of cortical areas and their subdivisions of the immersion-fixed human brain. WFA binding showed an area-specific distribution pattern within areas 1, and 3a-3b of the somatosensory cortex as well as in the primary motor areas 4a-4p. The WFA binding labeled stripes of 150-175 microm width at intervals of 800-1000 microm within the motor cortex but not in the somatosensory cortex. At the cellular level, differences in staining intensities among certain cell types were evident among WFA-positive glial cells. WFA binding seems to be a useful marker to reveal areal borders and function related intraareal specializations in combination with immunocytochemical techniques. PMID- 11195089 TI - Retarded myelination in the lumbar spinal cord of piglets born with spread-leg syndrome. AB - Piglets born with spread-leg syndrome, a congenital weakness of the hindlimb adductors, were investigated to determine the site of lesion leading to limb impairment. Histological and immunohistochemical studies of the motor neuron unit showed no alterations but quantitative analysis revealed a reduction of axonal diameter and myelin sheath-thickness of the fibres innervating the adductors of the affected limbs. In the lumbar spinal cord a lack of myelination was observed in the tracts descending to the lower motor neurons. Recovery from the syndrome was accompanied by a catching-up of myelination with that of the controls. The spread-leg syndrome is due to a nutritional deficiency in the sow; thus it is assumed that the deficient maternal substances, mainly choline and methionine, are essential for the normal myelin production by spinal white matter oligodendrocytes of the fetus. PMID- 11195090 TI - Distribution of somatostatin-28 (1-12) immunoreactivity in the diencephalon and the brainstem of the dog. AB - The term somatostatin refers to a family of peptides, mainly somatostatin-14, somatostatin-28 and somatostatin-28 (1-12), which are the cleavage products of a single 116 amino acid-long preprosomatostain molecule. The production of antibodies to these peptides allows their localization in a number of neuronal populations throughout the entire neuroaxis in many mammals. The dog has been pointed out as an extremely useful animal model for studying age-related cognitive dysfunction and other neuronal changes associated with aging in which somatostatin appears to be involved. However, only very scanty information is available with regard to the distribution of somatostatin in the brain of the dog. In the present work we have determined the pattern of the distribution of somatostatin-28 (1-12) immunoreactivity in the diencephalon and the brainstem of the dog. High to moderate densities of labeled perikarya were found in the anterior periventricular and arcuate hypothalamic nuclei, the reticular thalamic nucleus, in delimited parts of the nucleus of the brachium inferior colliculus, the retrorubral area, the dorsal raphe nucleus, the myelencephalic reticular formation and the dorsal motor nucleus of the vagus. Less dense population of somatostatin cells were localized in other diencephalic and brainstem nuclei. The distribution of labeled fibers was even broader as in addition to those above mentioned there were a number of areas that appeared devoid of labeled perikarya. Many of the findings were similar to those reported in earlier works while others underlined the existence of inconsistencies in the distribution pattern of this peptide in the brain of mammals. PMID- 11195091 TI - A primary culture system of rat olfactory bulb forming many synapses similar to intact ones and spontaneously generating synchronous intracellular calcium oscillations. AB - Previously, several studies attempting to analyze olfactory functions using dissociated culture systems of the olfactory bulb (OB) have been reported. Reciprocal dendrodendritic synapses between secondary neurons (mitral/tufted cells) and interneurons (periglomerular/granule cells) are considered to play the most important role in signal processing in the OB. However, it is unclear whether these reciprocal synapses are formed in vitro in the same way as they are in the intact OB. Thus, we synaptologically investigated the nature of cultured OB neurons. These neurons from embryonic rats were classified into four groups based on the size of their somata and their glutamic acid decarboxylase (GAD) immunoreactivity. At 14 days in vitro, most of the neurons synchronously showed spontaneous intracellular Ca2+ oscillations that were reversibly inhibited by application of D-APV and CNQX. Moreover, the frequency of the oscillations decreased and their amplitude became larger following application of bicuculline. These results suggest functional glutamatergic synaptic coupling and inhibitory GABAergic synaptic modulation. Immunocytochemical staining revealed many dot-like products (puncta) that were immunoreactive to GAD as well as to synaptophysin surrounding the cultured neurons. These results strongly indicate the presence of GABAergic synapses. The existence of synaptic contacts in OB neuron cultures was also confirmed by electron microscopy. Two types of synapses, symmetrical and asymmetrical, were morphologically recognizable. Moreover, we could also identify peculiar synapses resembling the in vivo reciprocal dendrodendritic synapses. The use of these primary culture systems will facilitate the elucidation of mechanisms underlying olfactory functions. PMID- 11195092 TI - Uptake of aflatoxin B1 and T-2 toxin by two mycotoxin bioassay microorganisms: Kluyveromyces marxianus and Bacillus megaterium. AB - Uptake of aflatoxin B1 (AFB1) and trichothecene T-2 toxin from growth medium by mycotoxin bioassay strains of Klutyveomyces marxianus and Bacillus megaterium was assessed by incubating, washing, and sonicating the cells, extracting samples with chloroform, and analysing the extracts by a combination of high-performance thin-layer chromatography (HPTLC) and fluorescence densitometry. Using cultures of K. marxianus, the entire AFB1 dose was recovered and no AFB1 metabolites were detected. Less than 1% of the AFB1 was recovered from the cells, and AFB1 did not inhibit growth. Methanol in the incubation medium had no significant effect on the levels of AFB1 associated with K. marxianus cells. The entire dose of T-2 toxin was also recovered from K. marxianus cultures, and no metabolites were detected; again, less than 1% of T-2 toxin was cell-associated, but growth was completely inhibited. AFB1 partially inhibited the growth of B. megaterium; approximately 12% of the dose could not be recovered, and no AFB1-related metabolites were detected. Methanol increased the levels of recoverable AFB1 associated with B. megaterium cells. In the case of T-2 toxin, around 8% of the dose was not recovered, and no metabolites were detected; growth of B. megaterium was stimulated. These results suggest irreversible binding of both toxins, or derivatives of them, to the cells of B. megaterium. PMID- 11195093 TI - The use of morphomutants to investigate septum formation and cell separation in Schizosaccharomyces pombe. AB - Cytokinesis in the fission yeast Schizosaccharomyces begins by formation of a medially placed actomyosin ring, continues by progressive development of a septum, and is completed by cleavage of the mature septum to bring about cell separation. The cytological analysis of the Schizosaccharomyces pombe morphomutants sph2-3 and sep1-1 presented here demonstrates that the medial actomyosin ring colocalizes to the leading edge of the centripetally growing septum, and cleavage of the septum is triggered by rupture of the mother cell wall at the septal basis. PMID- 11195094 TI - Characterisation of coupling products formed by biotransformation of biphenyl and diphenyl ether by the white rot fungus Pycnoporus cinnabarinus. AB - Cells of the white rot fungus Pycnoporus cinnabarinus grown in glucose were able to hydroxylate biphenyl and diphenyl ether, although growth was inhibited by these substrates at concentrations above 250 microM. 2- and 4-Hydroxybiphenyl were detected as products of biphenyl metabolism and 2- and 4-hydroxydiphenyl ether as products of diphenyl ether metabolism in the culture media. After addition of 2-hydroxydiphenyl ether and 2-hydroxybiphenyl to cell-free supernatants containing laccase as the only ligninolytic enzyme, different coloured precipitates were formed. HPLC analysis revealed the formation of additional hydrophobic metabolites with one major product per transformation. Mass spectrometric analysis of the methyl derivatives of the polymer mixture indicated dimers and trimers with different binding types. The main products were identified as dimers with carbon-carbon bonds in para-position to the hydroxyl group of the monomers by mass spectroscopy and nuclear magnetic resonance spectroscopy. PMID- 11195095 TI - The Myxococcus xanthus wbgB gene encodes a glycosyltransferase homologue required for lipopolysaccharide O-antigen biosynthesis. AB - Myxococcus xanthus is a gram-negative soil bacterium that initiates a complex developmental program in response to starvation. A transposon insertion (Tn5-lac omega109) mutant with developmental deficiencies was isolated and characterized in this study. A strain containing this insertion mutation in an otherwise wild type background showed delayed developmental aggregation for about 12 h and sporulated at 1-2% of the wild-type level. Tn5-lac omega109 was found to have disrupted the M. xanthus wbgB gene, which is located 2.1 kb downstream of the M. xanthus lipopolysacharide (LPS) O-antigen biosynthesis genes wzm wzt wbgA. The deduced polypeptide sequence of WbgB shares significant similarity with bacterial glycosyltransferases including M. xanthus WbgA. The wbgB::Tn5-lac omega109 mutant was found to be defective in LPS O-antigen synthesis by immunochemical analysis. Further mutational analysis indicated that the defects of the wbgB::Tn5-lac omega109 mutant were not the result of polar effects on downstream genes. Various motility assays demonstrated that the Tn5-lac omega109 mutation affected both social (S) and adventurous (A) gliding motility of M. xanthus cells. The pleiotrophic effects of wbgB mutations indicate the importance of LPS O-antigen biosynthesis for various cellular functions in M. xanthus. PMID- 11195096 TI - A stable archaeal pyruvate carboxylase from the hyperthermophile Methanococcus jannaschii. AB - The pyruvate carboxylase (PYC) of the hyperthermophilic, strictly hydrogenotrophic, autotrophic and marine methanarchaeon Methanococcus jannaschii was purified to homogeneity. Optimal activity was at pH 8.5, > or = 80 degrees C, and a KCl concentration of 0.175 M. This enzyme is the most thermophilic PYC so far studied. Unlike the Methanobacterium thermoautotrophicum enzyme, Mc. jannaschii PYC was expressed in cells grown without an external source of biotin and in the purified form was stable during storage at 4, -20 and -80 degrees C. However, it was rapidly inactivated at 80 degrees C. The enzyme was insensitive to aspartate and glutamate, mildly inhibited by alpha-ketoglutarate, and was strongly inhibited by ATP and ADP (apparent Km, for ATP, 0.374 +/- 0.039 mM; apparent Ki for ATP, 5.34 +/- 2.14 mM; Ki for ADP, 0.89 +/- 0.18 mM). It was also strongly inhibited when the Mg2+ concentration in the assay exceeded that of ATP. Thus, this stable PYC could serve as a model for mechanistic studies on archaeal PYCs. It was apparently an alpha4beta4-type PYC composed of a non-biotinylated 55.5-kDa subunit (PYCA) and a 64.2-kDa biotinylated subunit (PYCB). The determined NH2-terminal sequences for these subunits provided additional support for our earlier proposal to rename the ORFs MJ1229 and MJ1231 in the NCBI Mc. jannaschii genome sequence database as PYCA and PYCB, respectively; even very recently, these have been misidentified as a subunit of acetyl-CoA carbxoylase (AccC) and the alpha-subunit of ion-pumping oxaloacetate decarboxylase (OADalpha), respectively. PMID- 11195097 TI - Hydrogen production by methanogens under low-hydrogen conditions. AB - Hydrogen production was studied in four species of methanogens (Methanothermobacter marburgensis, Methanosaeta thermophila, Methanosarcina barkeri, and Methanosaeta concilii) under conditions of low (sub-nanomolar) ambient hydrogen concentration using a specially designed culture apparatus. Transient hydrogen production was observed and quantified for each species studied. Methane was excluded as the electron source, as was all organic material added during growth of the cultures (acetate, yeast extract, peptone). Hydrogen production showed a strong temperature dependence, and production ceased at temperatures below the growth range of the organisms. Addition of polysulfides to the cultures greatly decreased hydrogen production. The addition of bromoethanesulfonic acid had little influence on hydrogen production. These experiments demonstrate that some methanogens produce excess reducing equivalents during growth and convert them to hydrogen when the ambient hydrogen concentration becomes low. The lack of sustained hydrogen production by the cultures in the presence of methane provides evidence against "reverse methanogenesis" as the mechanism for anaerobic methane oxidation. PMID- 11195098 TI - Isolation of human intestinal bacteria metabolizing the natural isoflavone glycosides daidzin and genistin. AB - Fecal bacteria from a healthy individual were screened for the specific bacteria involved in the metabolism of dietary isoflavonoids. Two strains of bacteria capable of producing primary and secondary metabolites from the natural isoflavone glycosides daidzin and genistin were detected. The metabolites were identified by comparison of their HPLC/mass, 1H NMR and UV spectra with those of standard and synthetic compounds. Both Escherichia coli HGH21 and the gram positive strain HGH6 converted daidzin and genistin to the their respective aglycones daidzein and genistein. Under anoxic conditions, strain HGH6 further metabolized the isoflavones daidzein and genistein to dihydrodaidzein and dihydrogenistein, respectively. The reduction of a double bond between C-2 and C 3 to a single bond was isoflavonoid-specific by strain HGH6, which did not reduce a similar bond in the flavonoids apigenin and chrysin. Strain HGH6 did not further metabolize dihydrodaidzein and dihydrogenistein. This is the first study in which specific colonic bacteria that are involved in the metabolism of daidzin and genistin have been detected. PMID- 11195099 TI - Simulation of the conformation of the murein fabric: the oligoglycan, penta muropeptide, and cross-linked nona-muropeptide. AB - The structure and conformation of the sacculus of bacteria at a scale much larger than just the component disaccharide penta-muropeptide is not well known and is crucially important for the understanding of bacterial growth and cell wall function. By computer simulations, the minimal energy conformations and the energy needed for stretching the component parts were found. The oligosaccharide chain, modeled as (GlcNAc-MurNAc)8 when under no tension, can assumed a variety of nearly iso-energetic conformations. These included a variety of bends and kinks, with the chain forming an irregular random coil. In the most relaxed and minimal energy state, the D-lactyl groups of the MurNAc (N-acetyl muramic acid) residues protruded at about an angle of 90 degrees relative to the D-lactyl groups of their immediate MurNAc neighbors in the same chain. The cell wall penta muropeptide precursor is identical for Escherichia coli and Bacillus subtilis; it also adopted many conformations, each of an energy almost equal to the global minimum. The cross-bridged structure of the tail-to-tail linkage of disaccharide nona-muropeptide has a second type of association, in addition to the covalent cross-bridge, which has not been considered before. This is the ionic interaction between the free D-Ala and the free amino group of the m-A2 pm. In vivo, when the cross-bridge is stretched (in the computer to simulate growth), this pairing dissociates. The possible biological significance of this is that it exposes the underlying 'tail-to-tail' peptide bond to autolysis and will expose both the ends of the m-A2 pm and the D-AlaD-Ala groups that may then be able to react with nascent penta-muropeptides to form trimers. This suggests a new model for growth of the bacterial cell wall that depends on changes in the chemical conformation of the cross-bridge structure as it comes to bear stress. PMID- 11195100 TI - Acetobacterium tundrae sp nov, a new psychrophilic acetogenic bacterium from tundra soil. AB - A new psychrophilic, anaerobic, acetogenic bacterium from the tundra wetland soil of Polar Ural is described. The organism fermented H2/CO2, formate, methanol, and several sugars to acetate as the sole end-product. The temperature range for growth was 1-30 degrees C with an optimum at 20 degrees C. The bacterium showed no growth at 32 degrees C. Cells were gram-positive, oval-shaped, flagellated rods 0.7-1.l x 1.1-4.0 microm in size when grown at 1-20 degrees C. At 25-30 degrees C, the cell size increased up to 2-3 x 10-15 microm due to a defect in cell division. The DNA G+C content of the organism was 39.2 mol%. Based upon 16S rDNA analysis and DNA-DNA reassociation studies, the organism was classified in the genus Acetobacterium as a new species, for which the name Acetobacterium tundrae sp. nov. is proposed. The type strain is Z-4493 (=DSM 9173T). PMID- 11195101 TI - Stable sulfur isotope fractionation during the reduction of thiosulfate by Dethiosulfovibrio russensis. AB - Stable sulfur isotope fractionation was investigated during reduction of thiosulfate by growing batch cultures of Dethiosulfovibrio russensis at a cell specific reduction rate of 2.4 +/- 0.72 fmol cell(-1) d(-1) (28 degrees C). Citrate was used as carbon and energy source. The hydrogen sulfide produced by this sulfur- and thiosulfate-reducing bacterium was depleted in 34S by 11% compared to total thiosulfate sulfur, in agreement with previous results observed for sulfate-reducing bacteria. This indicates the operation of a similar pathway for thiosulfate reduction in these phylogenetically different bacteria. PMID- 11195102 TI - Inducible expression and cellular location of AgrB, a protein involved in the maturation of the staphylococcal quorum-sensing pheromone. AB - AgrB has been suggested to be responsible for the posttranslational modification in staphylococci that leads to the production of the thiolactone-containing agr peptide pheromone. We demonstrate that AgrB is located in the cytoplasmic membrane. Vectors were constructed for the xylose-inducible overexpression of agrB, and of agrB and agrD together. A Staphylococcus epidermidis strain deleted for agr and containing these vectors was assayed for AgrB protein and pheromone production. The lack of adequate pheromone production suggests the involvement of additional factors in the production of the agr pheromone. PMID- 11195103 TI - A review of serious injuries and deaths among car occupants after motor vehicle crashes in Sweden from 1987 to 1994. AB - Car occupants injured in motor vehicle crashes (MVC) are a common problem in emergency departments. The aims of this study were to determine the incidence over time, according to the type of injury, age and sex distribution, mortality rate and geographical differences among all patients admitted to Swedish hospitals because of MVC injuries. Between 1987 and 1994, Swedish hospitals admitted 37,871 persons (51,348 admissions) who had been involved in MVC as drivers or passengers. There were 23,369 men and 14,502 women. The annual frequency of hospital admissions ranged from 5,943 to 7,175. There were 74.8 injured persons admitted per 100,000 of the population each year. Males between 16 and 24 years of age were more commonly involved. Injuries to the head and neck were particularly frequent (39%). Older persons, males, and passengers had a poor survival outcome. The incidence of injured car occupants was significantly higher in sparsly populated areas of Sweden. PMID- 11195104 TI - Anchor limited arthrodesis of the wrist. AB - We present a case of lunate dislocation with total disruption of all ligaments and, consequently, nutrient vessels. The injury was handled by fusion of the lunate with the scaphoid, capitate and triquetrum. This 'anchor fusion' has led to a very good long-term result. PMID- 11195105 TI - Glomangiopericytoma causing oncogenic osteomalacia. A case report with immunohistochemical analysis. AB - A 47-year-old woman suffered from gait disturbance due to back pain and muscle weakness. Laboratory data showed serum hypophosphatemia, elevated alkaline phosphatase, and a normal level of ionized calcium. Radiological examinations revealed multiple pathologic fractures in the ribs and pubic rami. She had had no episode of familial or any other notable disorder, and so she was initially treated with medication for adult-onset osteomalacia. However, 19 years later (when she was 66 years old), she noticed a soft-tissue tumor in her buttock. The tumor was excised. The histological features were those of glomangiopericytoma characterized by both glomus tumor-like and hemangiopericytoma-like structures. After removal of the tumor, her symptoms disappeared immediately. Laboratory data normalized 8 months later. To our knowledge, this is the first report of oncogenic osteomalacia caused by glomangiopericytoma. PMID- 11195106 TI - Synovial chondromatosis of the glenohumeral joint: a rare condition. AB - The case of a 22-year-old man with synovial chondromatosis (SC) of the shoulder joint is described. A literature review confirmed that SC of the glenohumeral joint is very rare and that the etiology of the disease is still unknown. The diagnosis is often delayed, and the preferred form of management remains controversial. We consider magnetic resonance imaging (MRI) a valuable tool in detecting SC at an early phase and estimating the intrasynovial extent of the disease. Shoulder arthroscopy today represents an elegant treatment option for removing the chondromas and performing a partial synovectomy. It might, however, be insufficent in cases of involvement of the bicipital tendon sheath and other recesses of the joint. PMID- 11195107 TI - Forty-two year survival with bilateral Judet hip prostheses. AB - In this case report, a 70-year-old man is presented who had begun to suffer from ankylosing spondylitis when he was 12 years old and had been operated on because of bilateral hip ankylosis at the age of 21 years. The interesting aspect of this case is that both hips were replaced with Judet type prostheses, which survived for 42 years. PMID- 11195108 TI - Presacral tumor associated with the Currarino triad in an adolescent. AB - A 17-year-old woman presented with pain over the sacral region. Plain radiographs of the sacrum demonstrated a bony deformity of the sacrococcygeal region in the shape of a scimitar. Magnetic resonance imaging showed a cystic mass of the presacral region which appeared to be continuous with the dural sac. An anteroposterior view myelogram revealed caudal elongation of the dural sac, and on the lateral view it was recognized as an anterior meningocele. At surgery, we confirmed a connection between the presacral mass and the rectum. In light of the combination of a sacral bony deformity, presacral mass including meningocele, and mass-rectum connection, we made the diagnosis of the Currarino triad, which is a rare complex of congenital caudal anomalies. The patient underwent excision of the presacral mass. Histologic examination of the resected specimen revealed features of an epidermoid cyst. PMID- 11195109 TI - Osteoid osteoma of olecranon process of ulna in subchondral location. AB - We present a case of a 15-year-old girl with osteoid osteoma in an unusual subchondral localization of the olecranon. Unspecific complaints and minimal X ray findings at the onset of the disease led to an incorrect diagnosis and more than 2 years of inefficient treatment. PMID- 11195110 TI - Osteoid osteoma of the carpal bones. AB - Osteoid osteoma is a benign bone tumor that rarely localizes in the hand or the carpal bones. We report two cases of osteoid osteoma localized in two different carpal bones. Unremitting wrist pain was a major clinical symptom. Surgical treatment including excision of the nidus was dramatically curative. In young patients, osteoid osteoma should be considered in the differential diagnosis of chronic wrist pain. PMID- 11195111 TI - Patellar tension band wiring: a revised technique. AB - Using a modified AO tension band wiring technique to treat a patellar fracture has become popular and has achieved a high success rate. However, the technique of Kirschner wire insertion has not been considered in detail, which may migrate and consequently introduce fragments loss of reduction. A revised technique involving bending both ends of the Kirschner wires was prospectively studied. Sixty-eight consecutive patients were so treated, and 62 patients were followed up for at least 2 years (range 2-6 years). All fractures healed with a union rate of 100% (62/62) and a union period of 2.5 +/- 0.5 months. Skin irritation was noted in 2 patients (3%). All patients achieved a satisfactory result. We therefore recommend this revised technique to treat all patellar fractures because of its high union rate and low complication rate. PMID- 11195112 TI - The role of mini-fragment screw fixation in volar dislocations of the proximal interphalangeal joint. AB - Palmar fracture-dislocations of the proximal interphalangeal (PIP) joint are uncommon injuries, which can be associated with long-term complications if sub optimally treated. We report two cases of palmar fracture-dislocations of the PIP joint treated by open reduction and internal fixation using a single mini fragment screw. The long term results of hand and finger function were excellent. PMID- 11195113 TI - Isola spinal instrumentation system for idiopathic scoliosis. AB - Since the definition of three-dimensional components of the scoliotic deformity, there have been important improvements in the surgical treatment of the problem. A derotation maneuver was proposed as a treatment option with CD instrumentation, but the reports of imbalance and decompensation with this system repopularized sublaminar wiring and translation as a corrective maneuver. Isola spinal instrumentation is one of the modern systems that utilizes vertebral translation instead of rod rotation. This study analyzes the results of 24 patients with idiopathic scoliosis who had been followed up for at least 2 years, and were surgically treated with titanium Isola Spinal Instrumentation in the Department of Orthopaedics and Traumatology, Ankara Social Security Hospital. Patients were grouped according to the King-Moe classification. Patients with type III, IV or V curves received only posterior instrumentation while this procedure followed anterior release and discectomy in the same session in patients with type I or II curves. A translation maneuver was utilized in the correction of scoliotic curves using the cantilever technique, either alone or supplemented by sublaminar wiring with Songer multifilament titanium cables. This study aimed to elucidate the effects of this technique in the frontal and sagittal plane curves and the trunk balance. The balance was analyzed clinically and radiologically by measurement of the lateral trunk shift (LT), shift of stable vertebra (SS), and shift of head (SH) in vertebral units (VU). The postoperative correction was significant in the frontal plane for all types of curves (p < 0.05). The postoperative correction was 80.9% +/- 9.5% in type III curves. Overall, the mean Cobb angle of the major curve value in the frontal plane was 66.9 degrees +/- 18.8 degrees, and it was corrected by 62.8% +/- 20.1%. The correction loss of Cobb angles in the frontal plane was 5.4 degrees +/- 5.5 degrees at the last follow-up visit. A normal physiologic thoracic contour (30 degrees - 50 degrees) was achieved in 83.3% of the patients and normal lumbar contour (40 degrees - 60 degrees) in 66.7% of the patients in the sagittal plane. The correction was found to be significant in all balance values (p < 0.05). The postoperative correction in LT values correlated with the correction of the Cobb angle values in the frontal plane. All patients had complete balance (SH: 0 VU and SS: 0 VU) or balanced curves (0 VU < SH, SS < 0.5 VU).Finally, the study concluded that the translation maneuver, especially when used with the cantilever technique, resulted in high correction rates in the frontal plane. Additionally, the technique was also successful in obtaining normal sagittal contours and correcting balance values. PMID- 11195114 TI - The GSB total knee arthroplasty. A medium- and long-term follow-up and survival analysis. AB - From 1981 to 1987, 77 GSB-II total knee arthroplasties were implanted in 65 patients. There were 23 men and 42 women aged on average 60 years old (range 30 85 years). The diagnosis was osteoarthritis (OA) in 21 knees, rheumatoid arthritis (RA) in 44 knees, and other in 12 knees. A clinical and radiological follow-up was performed in two stages after a mean of 6.7 years (61 knees) and 14.8 years (22 knees) to assess the medium- and long-term results and to determine if deterioration had occurred after mid-term follow-up. A survival analysis was done with two endpoints: (1) revision, and (2) revision, moderate or severe pain and lost to follow-up (worst-case scenario). At the last follow-up 36 patients (44 knees) had died, 2 patients (2 knees) refused examination, and 3 patients (3 knees) were lost to follow-up. Six knees had been revised for malposition (1.3%), septic (3.9%) and aseptic (2.6%) loosening. The mean Knee Society score after 6.7 and 14.8 years was 85 points (OA 82 points, RA 87 points). Lateralisation, subluxation or dislocation of the patella was present in 8 of 17 knees at the last follow-up. The 6- and 15-year survival rates with revision as the endpoint were 95% (CI 89%-100%) and 87% (CI 65%-100%), respectively. For the worst-case scenario, the 6- and 15-year survival rates were 95% (CI 89%-100%) and 56% (CI 0%-100%), respectively. The medium- and long-term results of the GSB-II total knee arthroplasty were good, and a decline in the knee score did not occur beyond the mid-term follow-up. Patella complications were abundant, and a marked decrease in implant survival was noted when moderate or severe pain and lost to follow-up were included as endpoints. PMID- 11195115 TI - Fracture-dislocations of the elbow joint--strategy for treatment and results. AB - Between January 1993 and December 1996, 41 patients with fracture dislocation of the elbow joint were treated in our department. In 28 patients (median age 46 years, range 15-77 years; 16 male, 12 female), a clinical and radiological follow up was obtained after median 34 months (range 12-59 months). In addition to the humero-ulnar dislocation, isolated fractures were present in 13 patients and combined fractures in 15 (all with involvement of the radial head). Primary neurological deficits were found in 7 and open fractures in 3 patients. In 7 patients, primary definitive surgical therapy was carried out by open reduction and internal fixation. A two-step surgical management (initial closed reduction and immobilization, 5 patients with external fixator, 7 with plaster; secondary open surgical procedure) was performed in 12 and conservative treatment in 9 patients. According to the Leipzig Elbow Score, taking subjective, clinical and radiological criteria into consideration, 4 patients achieved 'excellent' and 5 patients a 'good' result. Ten patients were scored 'moderate' and 9 'poor'. The rate of secondary complications necessitating revision was 36%. Poor results were primarily caused by extensive initial soft-tissue damage, delayed definitive surgical therapy, and ectopic heterotopic ossification. In contrast, fracture localization and degree of arthrosis were not of significant importance for the final outcome. In fracture dislocations, the goal is a primary definitive surgical treatment aiming for early postoperative physiotherapy. PMID- 11195116 TI - Fifteen-year results of the Muller CoCrNiMo straight stem. AB - Between September 1980 and May 1982, 112 primary unilateral total hip arthroplasties with the original cemented M. E. Muller Straight stem (manufactured from Protasul-10, a CoCrNiMo alloy) were inserted in 109 consecutive patients, all combined with non-cemented, non-coated polyethylene RM cups. Forty-three patients (40%) died during the follow-up period, all with the implant in place. Of the 66 surviving patients, 2 (1.8%) were lost to follow-up, and 7 (6.3%) were unable to attend the 15-year clinical and radiological follow up. Eight stems (7.3%) had to be revised for aseptic loosening and 3 stems (2.7%), for septic loosening. The 15-year survivorship of the Muller Straight stem regarding aseptic loosening is, therefore, 92.7%. Forty-six patients with 49 total hip replacements could be evaluated clinically and radiologically after 15 years. The mean duration of clinical follow-up for these 46 patients (42.2%) was 14.8 years (range 12.8-16.5 years). There were 22 women (48%) and 24 men (52%). The mean age at the time of the operation was 62 years (range 38-80 years), and 78 years (range 59-93 years) at the time of the latest follow-up. The mean Harris Hip Score at the latest follow-up evaluation of the 49 hip joints was 85 points (range 34-100 points). Of the 46 patients, 39 (85%) had a good or excellent clinical result. Radiographic follow-up was performed for 49 hips: 35 (70%) had linear or focal osteolysis in one or more zones of the stem, but only 4 (8%) had evidence of definitive loosening (linear radiolucency of over 2 mm all around the stem). Subsidence of over 2 mm was found in 20 hips (41%), 6 of them within the cement mantle. There was no correlation between subsidence and pain. The cause for the poor results is primarily the high rate of aseptic loosening of the non coated, non-cemented all-polyethylene RM cups, with a loosening rate of 63% and a revision rate of 25% after 15 years. PMID- 11195117 TI - Pelvic fracture among polytrauma decedents. Trauma-based mortality with pelvic fracture--a case series of 74 patients. AB - Pelvic fractures (PF) sustained from accidents are commonly believed to be a major cause of mortality in polytraumatized patients. The purpose of this paper is to determine whether PF are usually the primary cause or a contributing cause of mortality in these patients. A 10-year retrospective review was performed of all polytrauma patients with PF who were admitted to, and died, at a large, level I trauma center. The pelvic injury was graded according to Schatzker and Tile into stable (type A), partially stable (type B), and unstable (type C). The injury severity score (ISS), which incorporates associated injuries and their potential impact on mortality, was calculated for all patients. For each patient, a separate subjective designation of the probable cause of death was determined. We identified 74 decedents with PF following deceleration trauma. The pelvic fractures were classified as 12 type A (16%), 36 type B (49%), and 26 type C (35%). The mean ISS was extremely high, 40.6 +/- 1.4 (range 18-75), more than four times the score for simply a severe PF. The ISS was also not significantly different among the three pelvic fracture groups (P = 0.613). The records subjectively identified PF as the precipitating cause of death in only 13% of the patients. In this study, patients who died with PF had an ISS that implicated at least one or two additional major visceral injuries. These data do not support the hypothesis that PF, regardless of its complexity, is the usual primary cause or the major precipitating event of death in the polytraumatized patient. In these patients, mortality appears to be a function of the associated injuries based on the ISS calculation. PMID- 11195118 TI - A review of halo vest treatment of upper cervical spine injuries. AB - Thirty-five relevant studies involving in total 682 patients with 709 different types of injuries were evaluated in a review to determine the outcomes after immobilisation in a halo vest for various injuries to the upper cervical spine between 1962 and 1998. Studies were analysed according to the type of injury pattern and in terms of the treatment outcomes following primary treatment with a halo vest. The following types of injuries were evaluated: odontoid fractures (n = 420), hangman's fractures (n = 172), other axis fractures (n = 75), Jefferson fractures (n = 26), C1 arch fractures (n = 9), atlantooccipital (n = 2) and atlantoaxial dislocations (n = 5). The ligamentary atlantooccipital dislocations never healed. All isolated Cl ring fractures healed completely. The isolated C1 arch fractures healed in 83% of the cases. The ligamentary atlantoaxial dislocations had a 60% rate of healing. Healing was noted in all isolated odontoid type I fractures, 85% of the isolated odontoid type II fractures, and 67% of the odontoid type II fractures with combined injuries. The isolated odontoid type III fractures had a 97% healing rate. The non-classifiable odontoid fractures had a healing rate of 85%. The stable C2 arch fractures (hangman's fracture) healed consistently in 99%, and 90% success was found for other C2 fractures. A halo vest can be recommended for patients with isolated Jefferson fractures, hangman's fractures, odontoid type III and type II fractures, with a low dislocation rate. The results of treatment with a halo vest were unsatisfactory with regard to combined injuries with an odontoid type II fracture. An overall healing rate of 86%, however, allows one to conclude that this treatment continues to be a good alternative to operative stabilisation of bone injuries to the upper cervical spine. PMID- 11195119 TI - Surgical or conservative treatment for chronic rotator cuff calcifying tendinitis -a matched-pair analysis of 100 patients. AB - Conservative or operative treatment for rotator cuff calcifying tendinitis was investigated in 100 patients in a matched-pair analysis. They were examined clinically and ultrasonographically 35-60 months after the initial visit. The mean Patte score was 91.8 for the patients who underwent surgical treatment and 81 for the ones who received conservative therapy (p < 0.004), while the age related Constant-score was 103.4 and 95, respectively. Ultrasonography showed 28% calcifications in the surgical group, 18% newly formed and 10% that did not resolve after surgery. In the conservatively treated group, 33% calcifications were seen, of which 67% resolved. The number of rotator cuff ruptures was significantly higher in the conservative group. In the surgical group, 2% of partial tears and in the conservative group 5% of partial and 4% of complete cuff ruptures were found. Conservative treatment for calcifying tendinitis leads to less favourable pain results in the long term than surgical treatment. Surgery shortens the painful period and may reduce the number of future rotator cuff ruptures. Finally, the subjective functional outcome is significantly better after surgery. PMID- 11195120 TI - A model for assessing the rotational stability of uncemented femoral implants. AB - Permanent secondary stability of the uncemented femoral stem of hip prostheses can only be achieved once primary rotational and axial stability has been ensured. Rotational stability means that the stem is resistant to the articular forces that induce rotation around the implant's longitudinal axis. The 10-year survival rates of two uncemented conical shaped stems with decisively different proximal shapes were significantly different (Schenker SK 63.9%, Zweymuller SL 97.0%). The shapes were analyzed biomechanically by testing rotational stability in a silicone model. A reduction in the mediolateral height of the metaphyseal part by one-third led to a 20% smaller angle of ascent (P < 0.01), which indicated lower resistance. The proximally broader (mediolateral) prosthesis therefore proved to have better rotational stability. The study confirms that aseptic stem loosening is attributable to the design of the proximal part of the prosthesis. PMID- 11195121 TI - Effect of preoperative chemotherapy on the outcome of surgical treatment of vertebral tuberculosis: retrospective analysis of 434 cases. AB - A retrospective analysis of 434 patients with vertebral tuberculosis who were treated surgically was performed with special reference to the preoperative duration of chemotherapy. Of these, 376 underwent 4 weeks of a chemotherapy regimen with isoniazid, rifampin and ethamburol, and in 2 re-activation of the disease was observed. The remaining 58 underwent operation for neurological impairment with 6-18 h of the same chemotherapy regimen, and in no case did re activation occur. These results suggest a shorter duration of chemotherapy may be utilised in all patients undergoing surgical treatment for vertebral tuberculosis, providing a thorough debridement is performed, leaving no necrotic or infected tissue behind. PMID- 11195122 TI - Surgical treatment of tibial plateau fracture in elderly patients. AB - This retrospective study involves 22 patients with displaced tibial plateau fractures who were treated surgically from July 1993 to April 1996. All the patients were over 60 years old (mean 66.3 years old, range 61-80 years). All of the patients were treated by open reduction and internal fixation with AO/ASIF buttress plates (Synthes, Bochum, Switzerland). Additional small fragment plate or inter-fragmental screws were used in some of them as indicated. Two patients died during follow-up of causes unrelated to the fractures. The average follow-up time was 49.8 months (range 36-68 months). The other 20 patients were interviewed at the outpatient clinic, and radiographs of bilateral standing knees were taken. By comparison with the uninjured side on radiographs, condylar joint space depression was noted in 6 patients. However, joint depression greater than 4 mm was not found. Malalignment with varus or valgus greater than 5 deg was not demonstrated in any case. Their range of motion was restored in all patients, with more than 120 deg of flexion and without extension lag except for the one who suffered a superficial wound infection. No complication required further surgical management. During the period of follow-up, no accelerated degenerative change in the operated knee joint resulted in total knee arthroplasty. Two patients needed occasional medical treatment for residual knee joint pain. Only two patients needed canes for assistance during walking due to old age and minor stroke. The results justify surgical treatment for displaced tibial plateau fractures in elderly patients. PMID- 11195123 TI - The role of clinical examination and risk factors in the diagnosis of developmental dysplasia of the hip: a prospective study in 188 referred young infants. AB - In this prospective study, the role of clinical examination and risk factors in the diagnosis of developmental dysplasia of the hip (DDH) was analysed. For this purpose, 376 hips of 188 referred infants with an average age of 3.7 months (range 0-8 months) were clinically and ultrasonographically (Graf method) examined. Infants who had at least one risk factor for DDH had a three times higher occurence rate of DDH than those who didn't have any. Breech presentation and positive family history were the two most common risk factors associated with DDH. The rate of DDH was nearly 16 times higher in the hips with at least one abnormal clinical finding than in the ones without any. Ultrasonographically unstable hips (type IIc-unstable to type IV) were always detected during clinical examination. There was a risk of missing the diagnosis of hips with acetabular dysplasia alone. Limitation of abduction and asymmetry of the skin folds were the two most common clinical findings associated with DDH. Nearly two-thirds of the infants with at least one positive clinical finding and at least one risk factor had either an unilateral or bilateral dysplastic hip. It was concluded that a careful clinical examination was significantly more important than the coexisting risk factors in the detection of DDH. PMID- 11195124 TI - Ipsilateral fracture of the femoral neck and shaft, treatment by reconstruction interlocking nail. AB - This study involved nine patients with ipsilateral fractures of the neck and shaft of the femur. They were all male with an average age of 28.5 years. All of the fractures resulted from high-energy trauma. The neck fracture was initially missed in one case. All fractures were fixed by a Russell-Taylor reconstruction femoral nail. Surgery was delayed for an average of 6.6 days (range 2-21 days). The patients were followed up for an average of 2.1 years. All fractures healed; the average time of union for the neck fracture was 4.2 months (range 3-6 months) and for the shaft fracture, 6.9 months (range 4-18 months). A delay in surgery did not affect the union rate. There were no cases of avascular necrosis or non union of the femoral neck fracture. One hip healed into mild varus, one shaft fracture had a delayed union, and one developed a late infection of the femoral shaft. The use of the reconstruction nail offers superior stabilization over other currently used methods and is associated with fewer complications. PMID- 11195125 TI - Osteoporosis in patients with paralysis after spinal cord injury. A cross sectional study in 46 male patients with dual-energy X-ray absorptiometry. AB - In a cross-sectional study, 46 male patients with paralysis after spinal cord injury (average age 32 years; injuries sustained from 1 to 26 years ago; 33 Frankel A, 13 Frankel B, C, D) were examined clinically and by dual-energy X-ray absorptiometry (DEXA). Their bone mineral density (BMD) values were compared with age-related controls and correlated to clinical parameters. BMD was reduced in the proximal femur (p < 0.05) and the distal forearm (p < 0.05), but not in the lumbar spine. Demineralisation was influenced in the proximal femur (Z-score 2.95) by immobilisation after surgical treatment. Patients suffering from complete lesions had significantly lower BMD in the lumbar spine (-1.47) compared with patients with incomplete lesions (+0.02). BMD was not significantly influenced by the level of the lesion and the ambulatory status. Long-term monitoring showed significant demineralisation in the proximal femur (r = -0.36) and the distal forearm (r = -0.4), but not in the lumbar spine (r = -0.21). By correlating BMD with clinical parameters, it can be deduced that, firstly, immobilisation after surgical treatment should be reduced to a minimum; secondly, that every effort must be expended to prevent turning an incomplete into a complete lesion; and finally, that rehabilitation treatment should be lifelong. PMID- 11195126 TI - Adaptation of Ilizarov ring fixator to the economic situation of developing countries. AB - Especially in countries with low per capita income, poor patients with open fractures and non-unions are unable to purchase modern, commercially produced surgical implants. To alleviate this situation, we initiated the production of a locally made ring fixator. The rings were cut from tubes cast from scrap aluminium. It was applied in 40 patients to test its utility for the typical indications for the Ilizarov technique. The fixator was tolerated well. All fractures united except in one case where there was refracture of the consolidate due to too early removal of the fixator. Two arthrodeses were successful. Bone transport showed adequate regeneration. A single radial non-union united successfully. Loosening occurred in 11 wires and breakage in 6. The subacute infections in 11 (27.5%) patients were not due to the fixator itself but to low standards of hygiene and the delay of treatment in the prehospital phase. Reusing the fixator at least three times reduces the cost for the individual patient to US$ 13.60. A locally made fixator is cost-effective and can be recommended for surgical treatment under similar economic situations. PMID- 11195127 TI - Treatment of stages 2 and 3 giant-cell tumor. AB - During the period from August 1986 to August 1992, we treated 23 patients with giant cell tumors stage 2 or 3, according to the classification by Campanacci et al.. We analyzed the therapeutic options, complications, local recurrence rate, and functional results after a mean follow-up of 56 months (range 31-89 months). Intralesional resections were performed in 15 and wide resections in 8 patients. The majority of intralesional resections were performed for stage 2 tumors and the majority of en-bloc resections for stage 3 tumors. The overall local recurrence rate was 8.7%, but we observed local recurrence only in intralesional resections. Our experiences suggest that a subtle surgical technique with respect to oncological requirements is the most important element in the avoidance of local recurrence. Stage 2 tumors associated with weight-bearing anatomical structures should be treated with intralesional curettage and bone cement. Stage 3 tumors are limited as to their surgical options and are determined in some cases by their localization and the degree of bone destruction. Wide resections should be reserved mainly for stage 3 tumors. PMID- 11195128 TI - Early mobilization after sliding and Z-lengthening of heel cord: a preliminary experimental study in rabbits. AB - Sliding lengthening and Z-lengthening techniques are widely used in heel cord lengthening. Even though most surgeons performing these procedures apply a short leg cast after surgery, their postoperative immobilization intervals vary from 3 to 7 weeks. Nather et al. showed that there was no need for immobilization after the musculotendinous lengthening of long, deep flexor tendons. In the present study, we aimed to show the healing process of heel cords lengthened by sliding and Z-plasty lengthening in rabbits that did not undergo any postoperative immobilization. We performed sliding lengthening in the right heel cords of the rabbits and Z-lengthening in the left heel cords. We compared these two techniques radiographically, biomechanically, and histopathologically. Even though the biomechanical study showed superior results in the sliding lengthening group on the 7th day, elongation of the tendons at both sites was seen radiographically. There was no statistically significant difference between the sites according to the biomechanical study done on the 28th day. We concluded that the ankle should be immobilized in the early healing phase and that both types of lengthening gain a similar level of strength by the 4th week. PMID- 11195129 TI - Septic arthritis of a lumbar facet joint due to pyonex. AB - We present a case of septic arthritis of a lumbar facet joint with an associated epidural abscess. A 13-year-old boy was hospitalized with acute severe back pain and fever after pyonex was done. The infection was precisely localized with magnetic resonance imaging, bone and gallium scintigraphy. He responded to antibiotic therapy. We suppose that the infection was caused by pyonex because the blood cultures were negative, and the patient had an abrupt onset of severe pain and fever 24 h after the acupuncture. PMID- 11195130 TI - Primary intramuscular hydatidosis of supraspinatus muscle. AB - Hydatid disease of the muscle is very rare and represents approximately 3% of all patients with hydatidosis. Since the infection closely resembles a soft-tissue tumor on clinical examination, the preoperative radiologic diagnosis is very important to avoid biopsy. We report an unusual case of primary intramuscular hydatidosis with its magnetic resonance imaging appearance, clinical and pathological findings. PMID- 11195131 TI - Flexor digitorum longus accessorius in the club foot of an infant with Nager syndrome. AB - The case of a male infant is reported who had club foot on the right side and pes adductus on the left side in combination with acrofacial dysostosis; he also demonstrated preaxial anomalies of the upper limbs indicative of Nager syndrome. In addition, an unusual aberrant muscle was discovered during surgical correction of the right club foot. PMID- 11195132 TI - Periscapho-lunate dislocation. AB - A case of a volar periscapholunate dislocation is reported. Treatment by closed reduction and Kirschner wire fixation gave a good clinical result. PMID- 11195133 TI - No neurological involvement for more than 40 years in Klippel-Feil syndrome with severe hypermobility of the upper cervical spine. AB - We report the case of a 42-year-old woman with Klippel-Feil syndrome, who showed severe hypermobility of the upper cervical spine without neurological involvement for more than 40 years. Radiographs revealed the presence of the odontoid bone and fusion of the atlas, odontoid bone, and occiput. Congenital fusion was present from the axis to C5 as a block vertebra. Lateral flexion-extension radiographs revealed severe hypermobility at the junction between the odontoid bone and the axis. Prophylactic surgical stabilization has been recommended in patients with severe hypermobility, but adjacent disc problems may possibly occur at the unfused levels in the future. We believe that early prophylactic stabilization should not be indicated for Klippel-Feil syndrome without neurological involvement only because of hypermobility. PMID- 11195134 TI - Alcohol drinking and cigarette smoking: a "partner" for gastric ulceration. AB - Alcohol consumption and cigarette smoking are two etiologic factors that have a close relationship with peptic ulcer diseases. Chronic active gastritis is reportedly associated with chronic alcohol ingestion. Nonetheless, the inflammatory changes are likely to be related to concurrent Helicobacter pylori infection that is common among alcoholics. Moreover, chronic alcoholism is also correlated with the presence of gastric metaplasia. Both clinically and experimentally, alcohol had been shown to affect the mucosal barrier and histology. These ulcerogenic effects play a crucial role in altering gastric mucosal defense mechanisms. Cigarette smoking is coupled with the initiation and prolongation of gastric ulcers. Epidemiologic data show that cigarette smoking increases both the incidence and relapse rate of peptic ulcer diseases and also delays ulcer healing in humans. Retrospective studies also indicate that cigarette smoking is a key factor in inducing ulcer diseases rather than a linked behavior. The general detrimental effects of cigarette smoking in the gastric mucosa include reduction of circulating epidermal growth factor, increase in tissue free radical production and the presence of free radicals in smoke, together with reduction of mucosal constitutive nitric oxide synthase activity. Furthermore, the alteration of normal gastric mucosal blood flow and angiogenesis and the suppression of cell proliferation contribute largely to the delay in ulcer healing in cigarette smokers. Concurrent consumption of alcohol and cigarette smoking significantly increases the risk of gastric ulcers. In animal experiments, cigarette smoking potentiated ethanol-induced gastric mucosal damage. The reduction of mucus secretion, increase in leukotriene B4 level, increased activities of inducible nitric oxide synthase, xanthine oxidase and myeloperoxidase, and the expression of adhesion molecules in the gastric mucosa accompanied such potentiating effects. Substances other than nicotine in cigarette smoke may also contribute to the above effects. PMID- 11195135 TI - Guided tissue regeneration with and without demineralized freeze-dried bone allografts for maxillary Class II furca invasions of rapidly progressive periodontitis. AB - BACKGROUND: Guided tissue regeneration (GTR) using an expanded polytetrafluorethylene (ePTFE) membrane is an established treatment modality for periodontal disease. This study was designed to compare the effects of ePTFE membranes with and without demineralized, freeze-dried bone allografts (DFDBA) for treating maxillary class II buccal furca invasions of rapidly progressive periodonitis. METHODS: Seven patients with pairs of maxillary class II buccal furca invasions comprised the study group. The clinical parameters investigated were probing depth, probing attachment level and marginal tissue recession. One defect from each pair of teeth was randomly selected for the ePTFE membrane and DFDBA group and the other tooth defect received ePTFE membrane treatment only. During the operation, horizontal probing depths at the buccal furcation areas were measured. The membrane was removed 6 weeks after insertion. All measurements were repeated 1 year later at surgical re-entry of the buccal furcation. The Wilcoxon ranked sum test was used to test the significance of the difference between the groups 1 year after treatment. RESULTS: In the ePTFE membrane and DFDBA group, the mean probing depth reduction was 2.1 +/- 0.8 mm. The probing attachment gain was 2.6 +/- 1.0 mm and the bone fill was 3.1 +/- 1.7 mm. There was no statistically significant difference between the groups for these parameters. The marginal tissue recession was reduced 0.4 +/- 0.7 mm in ePTFE membrane and DFDBA group but increased 0.9 +/- 0.6 mm in ePTFE membrane only group. This difference was statistically significant (p = 0.016). CONCLUSIONS: There was no difference in probing depth reduction, probing attachment gain or bone fill between the two treatment modalities for treating maxillary class II buccal furca invasion of rapidly progressive periodontitis. Marginal tissue recession can be significantly reduced with the treatment of combined ePTFE membrane and DFDBA. PMID- 11195136 TI - False positive molecular diagnosis of Leber's hereditary optic neuropathy. AB - BACKGROUND: The most common pathogenic mitochondrial DNA (mtDNA) mutation associated with Leber's hereditary optic neuropathy (LHON) is at the 11,778 nucleotide (nt) position and is usually detected by loss of an Sfa NI restriction site. However, Sfa NI restriction site includes five nucleotides. Substitution of any of the five nucleotides leads to loss of the cutting site and causes a false positive result. We investigated the false-positive diagnosis of LHON by loss of the Sfa NI restriction site using Sfa NI restriction site analysis and single strand conformation polymorphism (SSCP) analysis. METHODS: Mae III restriction analysis for double confirmation of the Sfa NI restriction site and direct sequencing for final confirmation of SSCP analysis were performed. RESULTS: The sensitivity of Sfa NI test was 100% and the specificity of the Sfa NI test was 97%. The false-positive rate of Sfa NI test was 3%. SSCP analysis showed 100% sensitivity. Direct sequencing showed 32 patients had a mutation at nt 11,778 of mtDNA and one patient had a silent mutation at nt 11,782 of mtDNA. CONCLUSIONS: These results suggest that restriction enzyme digestion analysis requires double confirmation to avoid a false-positive diagnosis and that DNA sequencing is needed for the confirmation of the mutation detected by SSCP. PMID- 11195137 TI - Review of pre-eclampsia in Taiwan: a multi-institutional study. AB - BACKGROUND: Because the reported frequency of pre-eclampsia in Taiwan varies significantly, the aims of this study were to measure the current incidence of pre-eclampsia and its correlated morbidity and mortality for both mothers and fetuses in Taiwan. METHODS: We retrospectively studied all reported cases of pre eclampsia and eclampsia from January 1, 1993 to December 31, 1997 in the 14 tertiary medical centers and regional hospitals in Taiwan. Recruiting criteria were pregnancy-induced hypertension (systolic blood pressure > or = 140 mmHg or diastolic blood pressure > or = 90 mmHg) with proteinuria (> or = 300 mg of urinary protein per 24 hours) and independent part edema. RESULTS: There were 4,193 patients with pre-eclampsia and eclampsia for a frequency of 2.03% of 206,551 deliveries during the study period. Of these, 58.9% of patients were classified as having mild pre-eclampsia while 38.4% had severe pre-eclampsia. Advanced maternal age (> 35 years) (odds ratio [OR] = 4.56; 95% confidence interval [CI] = 4.23-4.90; p < 0.001), primiparity (OR = 1.71; 95% CI = 1.61 1.82; p = 0.02) and twin pregnancy (OR = 1.92; 95% CI = 1.64-2.25; p = 0.01) were significant risk factors for developing pre-eclampsia. However, multivariate analysis showed that only advanced maternal age was a significant risk factor for pre-eclampsia (OR = 3.21; 95% CI = 2.95-3.50; p < 0.001). In contrast to mild pre eclampsia, severe pre-eclampsia resulted in significantly worse outcomes for both mothers and fetuses. Complications in patients with severe pre-eclampsia included placental abruption, acute renal failure, pulmonary edema, postpartum hemorrhage, pleural effusion, preterm labor, intrauterine growth retardation, stillbirth, neonatal mortality and low birth weight infants, all of which occurred significantly more frequently than in patients with mild pre-eclampsia (p < 0.001). CONCLUSIONS: Pre-eclampsia remains a big challenge in modern obstetrics in Taiwan. Early diagnosis and management of patients with pre-eclampsia to prevent progression would significantly improve outcomes for mothers and fetuses. PMID- 11195138 TI - Krypton-81m ventilation and technetium-99m macroaggregated albumin perfusion scintigraphy for detection of pulmonary embolism: the first experience in Taiwan. AB - BACKGROUND: This study was designed to assess whether the self-made (Institute of Nuclear Energy Research, Taiwan) krypton (Kr)-81m could be used as a ventilation agent to detect patients with suspected pulmonary embolism (PE). In addition, xenon (Xe)-133 ventilation scintigraphy was also performed for comparison. METHODS: Forty patients with suspected PE were studied. Each patient received Kr 81m ventilation, Xe-133 ventilation and technetium (Tc)-99m macroaggregated albumin (MAA) perfusion studies on the same day. Images were judged using the criteria of the modified Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). For those with a high or intermediate probability of PE on lung scans and normal pulmonary function tests, anticoagulants were given and patients were monitored with Tc-99m MAA perfusion studies after treatment. The final diagnosis was based on chest radiography, pulmonary function tests and lung scans. RESULTS: All 40 patients successfully underwent lung scans. Of these, 11 had PE. Ten of the 11 cases were detected using Kr-81m ventilation and Tc-99m MAA perfusion studies, resulting in a sensitivity of 91%. Seven of 11 cases were detected using Xe-133 ventilation and Tc-99m MAA perfusion studies, resulting in a sensitivity of 64%. Of the 11 patients with PE, four had PE alone; Kr-81m and Xe-133 results agreed in three patients, but Kr-81m detected PE in the remaining patient. Of the remaining seven patients who suffered from PE with obstructive airway disease, Kr-81m and Xe-133 agreed in four, but Kr-81m detected PE in another two patients and one case was missed by both studies. CONCLUSIONS: Self made Kr-81m was safe and effective for ventilation scintigraphy in humans. When Kr-81m was used for the detection of PE, it was particularly advantageous when PE occurred in small areas of the lungs or when the patient with PE had concurrent obstructive airway disease. PMID- 11195140 TI - Predictive efficacy of motion sickness history for airsickness. AB - BACKGROUND: Airsickness is a common problem in the early stage of flying training. It can be sufficiently severe to impair the student's flight performance and his ability to learn. Without adequate evaluation and rehabilitation, intractable airsickness symptoms will force student pilots to be permanently grounded. The purpose of this study was to evaluate the predictive efficacy of motion sickness history for airsickness of flight students. METHODS: A motion sickness history questionnaire with four different scores was used to predict airsickness of student pilots in the Air Force Academy. The questionnaire asked subjects questions about the severity and frequency of motion sickness symptom experienced in nine different motion sickness situations before and after 12 years of age. The results were grouped to four different scores. Pearson correlation and Student's t-test methods were used to evaluate the correlations of the four different scores. RESULTS: A total of 76 flight students in the class of 1997 who had under gone their flight-training course were included in this study. They were all healthy males with a mean age of 22.2 years (range, 20-24 years). The airsickness incidence of student pilots was 50%. The four different scores of motion sickness history questionnaire were highly correlated (r = 0.69 0.86, p < 0.01). The "after 12 years-of-age actually sick" score key had greater predictive validity for airsickness than the other motion sickness history questionnaire score keys and so did the "before 12 years-of-age feels sick" and "after 12 years-of-age feels sick" for no airsickness. CONCLUSIONS: The motion sickness history questionnaire was an efficient method to predict airsickness among Air Force student pilots. PMID- 11195139 TI - Statistics in ophthalmic research: two eyes, one eye or the mean? AB - BACKGROUND: Ophthalmic data, while different among individuals, are usually similar between fellow eyes of the same individual. This study was designed to illustrate alternative approaches to account for the correlation between fellow eyes. This is important for making inferences using data from both eyes. METHODS: With the use of a real data set from a population-based study, we described the distribution of intraocular pressure (IOP) by estimating the mean and standard deviation (SD) and evaluated the potential risk factors of higher IOP based on the regression method. The units of observation studied were of both eyes, right eye only, left eye only, the eyes with higher IOP and the mean value of both eyes. Furthermore, the generalized estimating equation (GEE) method was used to account for the correlation between fellow eyes in the regression analysis. Results and inferences from the different approaches were compared. RESULTS: The analysis included all the eyes, providing the largest sample size and unbiased estimates of the mean and SDs. There were some discrepancies among different approaches in the regression analysis. The GEE method simultaneously evaluated the effects of both eyes, and increased precision and enhanced inferences. CONCLUSIONS: Inconsistent results among different ophthalmic studies result from variations in not only study design and courses but also statistical methods. Making the best use of appropriate statistical techniques, which account for between eye correlation, provides valid statistical inferences. PMID- 11195141 TI - Type III tympanoplasty with cartilage obliteration for cholesteatoma surgery. AB - BACKGROUND: The main objective of cholesteatoma surgery is complete eradication of the disease. Another goal is to preserve hearing acuity. We reviewed type III tympanoplasty with cartilage obliteration for cholesteatomatous ears. To evaluate the role of ossiculoplasty, the functional results of classic and modified type III tympanoplasties were compared. METHODS: Thirty-six cholesteatomatous ears undergoing type III tympanoplasty with cartilage obliteration were reviewed. The same operator performed these operations from 1984 until 1995. According to the CAO staging system, there were five early, 16 moderate and 15 advanced-stage cases of cholesteatoma. Using the anterior approach, all operations were canal wall-down type III tympanoplasties with "tailored" open cavity and cartilage obliteration. There were 24 classic and 12 modified type III tympanoplasties. RESULTS: The average follow-up duration was 7.2 years. Neither recidivistic cholesteatoma nor retraction pocket was observed postoperatively. There was an improvement in atelectatic score after surgery. The mean postoperative air-bone gap (ABG) was 15.8 +/- 10.7 dB and the mean closure of the ABG was 4.0 +/- 14.3 dB. After the disease stage and preoperative hearing status were adjusted using regression analysis, there was no significant difference in hearing results between ears that underwent classic or modified type III tympanoplasties. CONCLUSIONS: We performed the canal-wall-down tympanoplasty with cartilage obliteration using the anterior approach for treatment of cholesteatoma. Such surgical techniques eradicate the cholesteatoma, prevent its recurrence and create a clean ear. Hearing reconstruction can also be accomplished in a single stage procedure offering a serviceable hearing acuity. PMID- 11195142 TI - [LII Annual Meeting of the Spanish Society of Neurology. Barcelona, 13-16 December 2000. Abstracts]. PMID- 11195143 TI - [Iron and cerebral infarct]. PMID- 11195144 TI - Parkinson's disease: quantification of disability based on the Unified Parkinson's Disease Rating Scale. AB - OBJECTIVES: To develop a simple measure for quantification of the disability (dependency) due to Parkinson's disease (PD). METHODS: PATIENTS: 65 nondemented PD outpatients, stage 1 to 5 of the Hoehn and Yahr Classification (HY). ASSESSMENT: HY, Schwab and England Scale, Northwestern University Disability Scale, Columbia University Rating Scale, Webster Scale, Barthel's Index, finger tapping, and timed "Up & Go" test. Six items from the ADL Section of the Unified PD Rating Scale (UPDRS)--as representative of the most basic ADL--were chosen to compose the UPDRS disability score (UDS), that was simultaneously rated by three observers. Global evaluations of disability by patient and physician were also recorded. STATISTICS: Descriptive, Cronbach alpha, kappa of Fleiss, Spearman rank correlation coefficients, Kruskal-Wallis test, and factor analysis. RESULTS: Internal consistency (Cronbach alpha = 0.86-0.87) and interobserver reliability (kappa = 0.84-0.98) were satisfactory. Convergent validity of the UDS with the applied PD rating scales (R = 0.76-0.92), global evaluations (R = 0.84-0.88), and timed tests (R = 0.47-0.65) was highly significant (all, p < 0.001). Distribution of UDS values across the HY categories showed significant trends (Kruskal-Wallis test, p < 0.001). A single factor explaining over 64% of the variance was identified. CONCLUSION: A simple and valid instrument for standardized evaluation of disability in PD is embedded in the UPDRS. PMID- 11195145 TI - [Prospective epidemiologic study of headache in ambulatory neurology service in the province of Palencia]. AB - OBJECTIVES: To study demographic data about the first time consultations for headache in our neurologic clinic, its diagnostic distribution, its diagnostic and therapeutic management by the neurologist, its source, and the influence of the primary care doctors formation in their search of neurological consultation and therapeutic management in patients with headache. PATIENTS AND METHODS: A protocol with several demographic clinical and medical care data of the all first time visits for headache in our province was picked up, during 3 consecutive months. RESULTS: Headaches represent 21.5% of the first time consultations. The majority of the patients were women. The primary care doctors sent 93.6% of patients. The two more common diagnoses were tension-type headache (60%) and migraine (25.4%), reflecting their prevalences in the population. The more common treatments were the associations of two drugs. The general doctors sent more patients with headache (3.36 per thousand and year) than family doctors (1.84 per thousand and year). The approximation between initial diagnosis (primary care doctor) and final diagnosis (neurologist) was 26.4%, greater for family doctors (38.1%) than for general doctors (23.9%). CONCLUSIONS: Headaches represent the first cause of neurological consultation. The diagnostic distribution of the patients sent to our province shows the prevalences in the population. The family medicine formation is useful for a better selection of the patients sent to neurologists and a better diagnostic approach. PMID- 11195146 TI - [Molecular basis of spinal muscular atrophy: th SMN gene]. AB - Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by degeneration and loss of motor neurons of the anterior horn of the spinal cord. The clinical manifestations include proximal symmetric weakness and progressive atrophy of muscle. SMA is classified by age of onset, severity of symptoms, and evolution in three groups: type I, severe or Werdnig-Hoffmann disease, type II or intermediate and type III, moderate-mild, Kugelberg-Welander disease. The identification of the SMN1 gene as determinant of SMA opened new alternatives to study the disease. Most of the patients have deletions and conversion of SMN1 and in a small number of cases, point mutations were detected. There is no obvious genotype-phenotype correlation because homozygous absence of SMN1 was associated to a wide spectrum of manifestations from congenital disease to non symptomatic cases. Modifier factors, such as the number of copies of SMN2, could influence the phenotype. Other possible modifier genes are under study. The SMN gene is expressed in various neuronal populations. However, only motor neurons are responsible for the manifestations of the disease. The SMN protein is part of a complex with various proteins involved in the splicing reaction. This apparent essential function for all cells could be critical in motor neurons. When SMN1 is absent or dysfunctional, the motor neurons could be more sensitive because they have an increased transcription activity. In this situation, other cells and tissues could be protected by genetic or cellular factors still undiscovered. PMID- 11195147 TI - From the Austrian Society of Neurology and Psychiatry to the Austrian Society of Neurology. PMID- 11195148 TI - [Bilateral polar infarct]. PMID- 11195149 TI - [Schwannoma of the olfactory groove]. AB - Solitary schwannomas arising from the olfatory groove are extremely rare. Only 15 other cases have been reported so far. A case of olfatory groove schwannoma in a 19-year-old man with seizures and without neurological deficits is described. CT scan and MRI showed a tumour in the left frontobasal region. Left frontal craniotomy and excision of the tumour revealed a tumour in the region of the olfatory groove attached to the cribiform plate. The pathology, origin, and clinical characteristics of olfatory groove schwannomas are reviewed. PMID- 11195150 TI - [Symptomatic cluster headache: presentation of 2 cases]. AB - Cluster headache is a primary headache with well-defined diagnostic criteria. Nevertheless, in 3-5% of patients this syndrome is secondary to diverse cranial structural abnormalities. Atypical features which suggest a secondary or symptomatic origin include absence of periodicity and regular hourly recurrence, persistence of background pain among attacks, unsatisfactory response to treatment, and presence of neurological signs other than ptosis or miosis. We present two patients with symptomatic cluster-like headache. In one, the syndrome was associated with a fistula of the right superficial temporal artery. After embolization the pain attacks ceased. The second patient presented a ventricular xanthoma, located in the occipital horn; after surgical excision, the pain attacks did not recur. The progressive increase in frequency and absence of regularly hourly recurrence of pain episodes was a common feature in both cases. We comment and revise the pathophysiology of this syndrome, with emphasis on the case of the xanthoma, since we did not find a similar case described. If a secondary cluster-like headache is suspected, neuroimaging studies should be done. PMID- 11195151 TI - [Isolated sensory trigeminal neuropathy caused by a lateral pontine infarct]]. AB - Lesion of cranial nerves due to vascular damage at pontine level generally associates affectation of near nerve tracts. Isolated fifth nerve palsy due to vascular pontine lesions has been scarcely reported. We present a hypertense 57 year old woman who suffered from sudden paresthesias and hypoesthesia on the three divisions of trigeminal nerve without motor involvement and with preservation of corneal and masseter reflexes. Cranial magnetic resonance showed small dorsolateral pontine infarct over the right fifth cranial nerve entry. Isolated sensitive trigeminal neuropathy is a rare debut form of pontine infarct. PMID- 11195152 TI - [Stuttering as the only manifestation of a cerebral infarct]. AB - A 53-year-old right-handed man acutely developed stuttering. On his examination there was blocks and repetitions exclusively on first syllables of words in conversational speech, improving in automatic tasks. There was neither aphasia, nor other neurological deficits. An MR imaging of the brain showed a circumscribed cortical infarct on the left precentral circunvolution. Cerebral angiography was consistent with atherosclerotic narrowing of the intracavernous segment of left internal carotid artery. Artery-to-artery embolism was the suggested mechanism for this stroke and the patient was treated with oral anticoagulants for six months. Stuttering improved progressively and the patient became asymptomatic a month after the stroke. Ictal acquired stuttering symptomatic of ischemic stroke without aphasia or other neurological deficit is exceptional. An small infarct on the left motor area as cause of isolated acquired stuttering adds new information about neural circuits involved in this phenomenon. PMID- 11195153 TI - [Acute dystonia secondary to treatment with betahistine]. PMID- 11195154 TI - [Iatrogenic pneumocephalus caused by epidural analgesia]. PMID- 11195155 TI - [Episodes of complete inversion of the visual image and protuberance infarct]. PMID- 11195156 TI - Willingness to pay for long-term care insurance system in a municipality in Tokyo. AB - This study attempted to estimate the valuation of Long-term care (LTC) insurance system among the residents in a municipality in Tokyo by applying the Willingness to Pay (WTP) approach. The mean WTP for Group one (those aged 65 and over) and Group two (those aged between 40 and 64) was estimated to be 13,305 Japanese Yen and 8,722 Japanese Yen, respectively. Both amounts exceed the contribution estimated by the Ministry of Health and Welfare (2,500 Japanese Yen). The result reflects a high expectation for the system especially among those in Group one. It also suggests that those in Group one may be able to shoulder more financial responsibility for the system. Further research on WTP for LTC insurance system is deemed beneficial for its successful management. PMID- 11195158 TI - Mental health in the developing countries of the Asia Pacific region. PMID- 11195157 TI - Caries risk factors among three-year old children in Chiba, Japan. AB - In order to predict the factors which affect the occurrence of dental caries in children after the age 18-months, we analyzed the relationship between the increment of the decayed, missing, and filled teeth (dmft) in children from 18 months to three-years of age and caries risk factors. Subjects were 392 infants who received both an 18-month-old check-up and a three-year-old check-up in Chiba city. Stepwise multiple logistic regression analyses were used to analyze the results with the increment of the dmft by various combinations of independent variables (sex, order of birth, sweets intake, beverage intake, tooth brushing and feeding). The most predictive factors for the increment of the dmft in upper anterior and molar were "breast feeding" and "bottle feeding" respectively. From these results, we concluded that bottle feeding and breast feeding were the risk factors for the increment of the dmft from the age of 18-months to three years. PMID- 11195159 TI - Depressive symptoms and cigarette smoking among Native Hawaiians. AB - The present study estimated the prevalence of depressive symptoms and cigarette smoking and examined the relationship between depressive symptoms and cigarette smoking among native Hawaiians. Cross-sectional data from 524 rural, native Hawaiian from the Native Hawaiian Health Research Project are presented. Depressive symptoms were measured using the self-report Centre for Epidemiological Studies--Depression Scale. Information on smoking behavior and sociodemographic variables was collected. The prevalence of depressive symptoms was 15%, and significantly higher among participants with lower educational attainment. The prevalence of current smokers was 32%, and significantly higher among younger adults and participants with lower educational attainment. Regression analyses reported a significant relationship between CES-D scores and smoking status as well as between CES-D scores and number of cigarettes smoked daily. However, when education and age were included in the regression models, the relationships were attenuated. The findings and implications of this study are discussed. PMID- 11195160 TI - Change in mortality and years of life lost attributable to tobacco in Japan, 1985 and 1995. AB - Despite the secular trend of decreasing prevalence of smoking and consumption of tobacco in most industrialized countries, the prevalence of smoking in Japan continues to be one of the highest. Based on the alternative measure of population attributable fractions, the present study gives an estimate of the number of deaths and the years of life lost (YLLs) attributable to tobacco in Japan for both 1985 and 1995. This study shows a considerable increase in mortality from tobacco-related diseases over the decade, in particular from lung cancer and chronic obstructive pulmonary disease, a consequence of the intensified exposure to tobacco in the early 1960s. Although the period of the highest exposure to tobacco was in the late 1970s, prevalence of smoking is still considerably high in Japan and the burden from tobacco will persist if proper anti-smoking measures are not implemented immediately. PMID- 11195161 TI - Analysis of birth weight data from the Malaysian Family Life Survey II. AB - An analysis of birth weight was undertaken on secondary data derived from the Malaysian Family Life Survey II. A total of 1629 last singleton live birth infants was analysed with the aim of identifying from the variables available potential risk factors for low birth weight. Univariate and subsequently multivariate analyses were carried out for this purpose. The incidence of low birth weight was 11.8 percent. Race, parity and prematurity were found to be significantly associated with low birth weight after controlling of the other variables. The findings indicate that more work needs to be done to establish the underlying reasons for low birth weight in Malaysia. PMID- 11195162 TI - Association of lifestyle parameters with the prevention of hypertension in elderly Japanese men and women: a four-year follow-up of normotensive subjects. AB - To study the association of lifestyle parameters with the future risk of hypertension in normotensive subjects, a baseline questionnaire and a four-year follow-up were performed in 445 normotensive Japanese at 35 to 89 years of age. In 60 to 69 year old subjects, the changes of blood pressure during four years were negatively correlated with the amount of boiled rice intake in men and with Japanese tea intake in women. Multiple logistic regression analysis revealed that miso-soup intake at two bowls per day or over was protective against hypertension during follow-up (p < 0.05). These results indicate that food intake is important in the prevention of hypertension in the elderly. PMID- 11195163 TI - The health impacts of pesticide use on sugarcane farmers in Fiji. AB - A survey conducted among sugarcane farmers in Fiji found significant differences in the incidence of chronic illness and disease between users of pesticides and a nonuser control group. Though average production of sugarcane was markedly higher among pesticide users, average annual medical expenditures were also significantly higher. Advanced technological methods including chemical pesticides require a system of institutional support to provide, inter alia, information for an effective transition from traditional to modern agricultural practices. Without that support the ad hoc application of technology may result in inefficiency and, in the case of pesticides, increased health risks among the farm population. Besides practical handling and application advice farmers require information describing the chronic health impacts of pesticide exposure to allow their weighing of the full costs of pesticide use against the production benefits. PMID- 11195165 TI - Cost analysis of malaria patients in Taikkyi Township Myanmar. AB - A hospital and clinic-based study was conducted in one malaria endemic area, Taikkyi Township, Yangon Division, Myanmar, for analysis of cost incurred by different types of malaria cases and the factors influencing the cost of illness from July to October 1995. A total of 100 patients admitted to hospital and 100 patients receiving ambulatory care from malaria clinics were interviewed using a structured questionnaire. Total cost of one episode of malaria was estimated to be kyats 559 for ambulatory care, kyats 2582 for an uncomplicated admitted case, kyats 4056 for one episode of cerebral malaria, kyats 4568 for one episode of other severe and complicated malaria and kyats 4758 for one episode of malaria with other disease. This study showed that the cost of illness for patients attending outpatient malaria clinics who received early diagnosis and prompt treatment was four to seven times cheaper than the cost of illness for hospitalized malaria cases. Multivariate analysis revealed the factors that contributed to high cost of care. Duration of illness before getting any type of treatment was the key factor that contributed to high or low cost of care. Long duration of illness before getting any type of treatment can lead to high malaria parasite density, long duration of actual illness and high total attendance cost. Therefore, it is recommended that people from malaria endemic areas should be informed to seek early treatment from health staff, and primary health care services should be made accessible to people who live in malaria endemic areas. The information obtained from this study will be useful in planning future malaria control programs and influencing policy makers to focus on timely and effective treatment of non-severe cases, which can save a large amount of economic loss due to treatment of severe malaria. PMID- 11195164 TI - High Toxoplasma seroprevalence associated with meat eating habits of locals in Nepal. AB - A serosurvey of Toxoplasma gondii infection in apparently healthy subjects (n = 404) living in Achham (n = 215) and Dang (n = 189) districts in western Nepal was carried out. An interview with 249 participants, each representing a household, was also conducted. This interview pertained to their meat eating habits and the keeping of cats in their houses. Toxoplasma antibodies were detected by using the microlatex agglutination test. The overall seroprevalence was 65.3% with no significant difference in the two districts (Achham: 66.9% and Dang: 63.5%) included (p = 0.546). Females and the Indo-Aryan ethnic-group showed marginally higher prevalence compared with their male (p = 0.545) and Tibeto-Burman (p = 0.075) counterparts. The majority of the infections was found to have occurred during childhood. The frequency of meat eating in western and eastern regions differed greatly (p = 0.000) with the people in the eastern region being frequent meat eaters than those in the western region. About one-third of the subjects, all Indo-Aryans, in the western region had the raw meat eating habit but none in the eastern region. Approximately 7.0% of households in both western and eastern regions kept cats. The present findings demonstrated a typical role of meat eating habits of people in the high Toxoplasma seroprevalence in Nepal. PMID- 11195166 TI - Airborne transmission of classical swine fever virus under experimental conditions. AB - Sixty-one pigs were housed in an isolation unit with three compartments and five pens. Each compartment had its own ventilation system resulting in air currents flowing from compartment A (pens 1 to 3) towards compartment B (pen 4), but not towards compartment C (pen 5). Classical swine fever virus was introduced by the experimental inoculation of one pig in the middle pen (pen 2) of compartment A. The virus infected the pigs in pen 4, following the prevalent air currents, and the compartmentalisation had only a retarding effect on the transmission of the virus. The absence of infection in the pigs in pen 5, which was not different from pen 4 except for the ventilation system, indicates that the spread of virus was affected by the air currents. PMID- 11195167 TI - Effects of a 1 per cent hydrocortisone conditioner on the prevention of immediate and late-phase reactions in canine skin. AB - Ten laboratory beagles were used to determine whether a 1 per cent hydrocortisone conditioner applied topically for three consecutive days would inhibit IgE mediated immediate and late-phase reactions induced in their skin. The trial was blinded, controlled with the product's vehicle and designed with a crossover. It consisted of three phases: one period without treatment (control phase) and two periods of treatment with either the active ingredient or the vehicle. Immediate and late-phase reactions were induced by the intradermal injection of rabbit anti canine IgE polyclonal antibodies. Twenty minutes after the intradermal challenge, the diameter of the wheal, but not the erythematous flares, were significantly reduced after the application of the active product. In contrast, IgE-mediated cutaneous late-phase reactions, evaluated by measurements of dermal thickness and eosinophil counts six hours after challenge and the numbers of dermal CD3 positive T lymphocytes after 24 hours, were not reduced by its application. PMID- 11195168 TI - Talocalcaneal luxation with plantar displacement of the head of the talus in a dog and a cat. AB - A dog and a cat suffered talocalcaneal luxation with plantar displacement of the head of the talus. Each case was associated with luxation of the talocentral joint and subluxation of the calcaneoquartal joint. The collateral ligaments were not significantly disrupted and this made it technically difficult to reduce the luxations. However, after open reduction, the luxations were inherently stable and a positional screw provided long-term stability. Both animals returned to their previous level of activity with no detectable signs of lameness. PMID- 11195169 TI - Long-term follow up of the effect of a pheromone therapy on feline spraying behaviour. PMID- 11195170 TI - Prevalence of shiga toxin-producing Escherichia coli in healthy slaughter pigs in Switzerland. PMID- 11195171 TI - Pulex irritans infestation in dogs. PMID- 11195172 TI - Vaccination for avian influenza in Italy. PMID- 11195173 TI - Neutering of dogs. PMID- 11195174 TI - [Chlamydia pneumoniae and its relation with human atherosclerosis]. PMID- 11195175 TI - [Transforming growth factor-beta (TGF-beta), keystone in diabetic nephropathy]. PMID- 11195176 TI - [Viral C hepatitis in patients with end stage renal disease. II. Viral genotypes]. AB - BACKGROUND: The hepatitis C virus infection is highly prevalent in patients on chronic dialysis. There are more than 10 variants of the hepatitis C virus, with 55 to 72% of identity among them at the amino acid level. However, we do not know the specific genotype in dialysis patients in Mexico. Thus, the aim of the present study was to know the specific genotypes of the C virus in infected dialysis patients, to know the distribution of genotypes in the different dialysis techniques and to know the relation between genotype and hepatic disease stage. METHODS: We performed a prospective, transversal and comparative study in patients in dialysis in three hospital centers in the south of Mexico City. The presence of C-type hepatitis infection was assessed by ELISA II and qualitative RT-PCR in blood samples. The genotype of the hepatitis C virus was determined by analysis of the restriction pattern of the RT-PCR product using Mva I, Hinf I, BstU I and ScrF I restriction enzymes. Variables analyzed were: age, gender, etiology of renal failure, kind and time in substitutive therapy, transfusion and hepatitis history, liver function test, blood urea, serum creatinine and blood cell count. RESULTS: We studied 235 dialysis patients that were divided following their dialysis modality into: 132 in continue ambulatory peritoneal dialysis (CAPD), 17 in CAPD, but with history of hemodialysis (PD/HD) of at least one month and 86 on hemodialysis (HD). The hepatitis infection was detected in 24 of the 235 patients (CAPD = 4.5%, PD/HD = 41.1% and HD = 12.7%; p < 0.001). The most common genotype was 1B (12/24), followed by 1A and 2A (4/24 each one), and finally by 2B and 2C (2/24 each one). We detected no patients with genotypes 3 to 6. The patients with 2A genotype were older than those infected with 1A (p < 0.05). History of surgery, transfusions, and hepatitis was similar in all genotypes. Finally the time in dialysis was longer in patients with 2A genotype than others (2A = 60.5 +/- 71.5 months, vs. 1A = 11.5 +/- 11.3, 1B = 26 +/- 26.4 y 2B/C = 17.5 +/- 13.4), but the difference did not reach statistical significance. The genotype distribution between dialysis techniques showed that 1B genotype was the most frequent in all modalities. The 1A genotype was present in similar proportions in patients of the three dialysis groups, the 2C genotype was present only in patients with CAPD. Finally, the 2B was only found in hemodialysis patients. DISCUSSION: The assessment of viral genotype revealed that 1B is the most common genotype in patients on chronic dialysis in Mexico City. The fact that the 1B and 1A genotypes were the most common types in our dialysis population suggest that transmission was similar to the general population, that is, probably by blood transfusions. PMID- 11195177 TI - Waldenstrom's macroglobulinemia is infrequent in Mexican Mestizos: experience of a hematological diseases referral center. AB - Along a 17-year period 7,373 patients were prospectively studied in a private practice Health facility; of these 11 were patients with Waldenstrom's macroglobulinemia; calculations from these data and previous publications show that this lymphoid malignancy represents in Mexico 0.18% of all hematologic malignancies, a figure 11 times lower than that described from caucasians. The median age was 65 years (range 31 to 84); there were 6 males and 5 females. Ten individuals were mexican mestizos, whereas one had a caucasian phenotype. The clinical features of the patients afflicted by the disease in Mexico were similar to those reported from caucasian populations. The median survival (SV) of the group of patients was 40 months, whereas the 42-month survival was 49%; the prognosis of the disease was relatively good despite the fact that complete remissions were unfrequent as a result of the treatment. PMID- 11195178 TI - [Non rheumatic pulmonary hemorrhage: case series description]. AB - INTRODUCTION: Pulmonary hemorrhage (PH) is characterized by diffuse hemorrhage from the pulmonary microvasculature. Its main features are dyspnea, hemoptysis, diffuse bilateral alveolar infiltrate and sudden fall in hemoglobin. Because the conditioning causes can be both: rheumatic and non-rheumatic, early recognition of the precipitating causes aids in orienting specific therapy. OBJECTIVE: To identify the clinical and paraclinical features of non-rheumatic PH and determine the associated mortality. METHODS: The charts of all patients diagnosed with HP in this institution between 1987 and 1997 were reviewed. OPERATIVE DESCRIPTIONS (DEFINITION): HP was confirmed by bronchoscopy, pulmonary biopsy, necropsy or at least three of the following criteria: a.--Sudden dyspnea, b.--Hemoptysis, c.--Hb decrease of 1 g/dL or more, d.--Recent alveolar infiltrate in the chest X-ray. STATISTICAL ANALYSIS: Descriptive statistics. RESULTS: Nine cases of non rheumatic PH were identified. Median age of patients was 34 years. Six cases corresponded to men, chemotherapy was associated in three patients. The duration from diagnosis of the underlying disease to HP was one to 73 months. All the patients presented dyspnea, crepitant ates tachycardia, decrease in Hb (median 2 g/dL), hypoxemia a mean of 53.4 mmHg. A diffuse interstitial pattern was evident in X rays of six cases; bronchoscopy was performed in three. Seven patients died, six because of massive pulmonary hemorrhage as the direct cause of death and one because of ARDS. CONCLUSIONS: PH occurs in hematological diseases accompanied by severe thrombocytopenia and progressive pulmonary infections. Because its associated with high mortality, early detection and treatment are of utmost importance. PMID- 11195179 TI - [Changes in brain serotonin biosynthesis in rats with diabetes mellitus induced by streptozocin: effect of insulin treatment]. AB - OBJECTIVE: To investigate if the changes in the activity of the tryptophan-5 hydroxylase and in brain serotonin synthesis provoked by diabetes mellitus persist or return to normal in the diabetic rats submitted to treatment with insulin. METHODS: Diabetes induced by the administration of streptozotocin in rats and their treatment with insulin was the paradigm used. At days 7, 14 and 21 of evolution, the brain serotonergic biosynthetic activity was evaluated. RESULTS: The diabetic rats showed a significant decrease of body weight. Also, they showed a low concentration of I-tryptophan, as well as a diminution in the activity of the key enzyme tryptophan-5-hydroxylase and its product serotonin in the cerebral cortex and brainstem. Interestingly, the activity of the enzyme was higher in the brainstem from day 14, accompanied with an elevation of the neurotransmitter. The diabetic rats submitted to treatment with insulin showed a complete physical recovery and a return to normal of plasma and brain I tryptophan. The activity of the enzyme not only normalized but was elevated and with an increase of serotonin in the brainstem and cerebral cortex. CONCLUSION: The present findings confirm that diabetes mellitus produced a chronic anabolic deficit and a decrease in some brain regions of serotonin synthesis. Also, demonstrate that the diabetic rats under specific treatment with insulin had a complete physical recovery and a return to normal of the serotonin precursor in the blood and brain. However, the activity of the limiting enzyme TrpOH case was elevated with an increase of the neurotransmitter in all regions studied. Since the diabetic animal, insulin treated, does recover metabolically, the mechanism of activation of the serotonin biosynthetic path in the brain may not be dependent on the decreased availability of its precursor the free plasma I tryptophan. Instead, it might be due to a change in the kinetics of tryptophan-5 hydroxylase, since its activity remains significantly increased in spite of plasma and brain normalization of its substrate. Altogether these changes in the biosynthesis of an important brain neurotransmitter may be of relevance in the pathophysiology of the psychoneurological complications in diabetic patients. PMID- 11195180 TI - [Circadian arterial blood pressure variation in non hypertensive type 2 diabetic patients]. AB - OBJECTIVE: To determine the characteristics of the blood pressure circadian rhythm in non-hypertensive type 2 diabetic subjects. MATERIAL AND METHODS: Cross sectional study on 57 individuals with type 2 diabetes without hypertension (31 women and 26 men) and 57 healthy subjects in a control group (29 women and 28 men). High blood pressure, renal or hepatic diseases were exclusion criteria. Using patient activated semiautomatic portable blood pressure recorder (Omron Healthcare Inc., Vernon Hills, Ill 60061), self-measured blood pressure of 24-h was registered. Subjects who blood pressure measures were not appropriately recorded in equal or more than 10% of the lectures were not included. RESULTS: The average systolic and diastolic blood pressure of 24-h was similar between the groups studied. The percentage decrease in the nocturnal systolic/diastolic blood pressure was of 4.6%/1.2% and 3.8%/6.8% for the diabetic women and men respectively, and of 8.6%/9.9% and 6.8%/8.2% in the control women and men. For the last nocturnal and first diurnal hours the systolic/diastolic blood pressure of diabetic subjects showed a lower increase with a higher duration than that observed for the control group. CONCLUSIONS: Non hypertensive type 2 diabetic subjects shown both nocturnal blood pressure fall of less than 10% and a lower increase, with prolonged duration in the first diurnal hours, than that observed in healthy subjects. PMID- 11195181 TI - [Classification of acute leukemias according to the first latin-american consensus conference for the immunophenotyping of leukemias]. AB - OBJECTIVE: To evaluate the recommendations of the First Latinamerican Consensus Conference for the Immunophenotyping of Acute Leukemia in untreated patients with de novo disease immunologically classified employing flow cytometry and an extended panel of monoclonal antibodies. MATERIAL AND METHODS: In that conference it was recommended the use of the following antibodies: cytoplasmic CD79a (cCD79a) and CD19 to define B-progenitor acute lymphoblastic leukemia (B-ALL); cCD3 and CD7 for T-cell ALL (T-ALL), and CD13, CD33 and myeloperoxidase (cMPO) for acute myeloblastic leukemia (AML). We analyzed the expression of these cellular antigens in 91 non-consecutive patients classified with the extended panel as: B-ALL 28 cases; T-ALL 7; B-T-ALL 2; AML 47; and mixed-lineage acute leukemia 7 cases. RESULTS: All 28 B-ALL cases were positive with each of the two recommended antibodies cCD79a and CD19, whereas in 24 AML cases (the expression of cCD79a was not assayed in 23 cases) and in 7 T-ALL patients both antigens were absent. cCD3 and CD7 antigens were identified in 71% and 100% of T-ALL, respectively. CD7 antigen was not detected in any of the 28 patients with B-ALL but it was expressed in 6 of 47 AML cases, while none of 75 B-ALL and AML cases were positive to cCD3. Forty nine percent of AML were positive for the three recommended markers: cMPO, CD13 and CD33, and 51% of AML cases reacted with one or two of these three monoclonal antibodies. Six out of 28 cases of B-ALL had aberrant expression of myeloid antigen (CD33 in 3 cases and CD13 in 3 cases). CONCLUSIONS: There was no difference in the definition of AL lineage between employing the extended antibody panel and that recommended by the Latinamerican consensus. PMID- 11195182 TI - [Thrombophilia, thromboembolism and the use of the unfractionated and low molecular-weight heparins]. AB - An overview of the key concepts about detection of thrombophilic states, establishment of risk factors for thrombosis, the current strategies on diagnosis of thrombophilia, as well as an analysis of the current experience with the use of fractionated and unfractionated heparins, is presented. It is well known that thrombotic disease is multifactorial and that its treatment must be interdisciplinary and multidisciplinary in order to perform an opportune diagnosis and to establish an adequate prophylaxis and anti-thrombotic therapy. Even though several advantages are observed when low molecular weight heparins are used, unfractionated heparins still have some specific indications. Furthermore, under specific conditions, they can work synergistically to achieve a maximal effect on the thromboembolic states. We propose that every medical unit should establish its own criteria and diagnostic and therapeutic algorithms that allow to detect, to diagnose, and to treat the thrombotic events in the best way thus diminishing the morbidity and mortality associated with these thrombotic events. PMID- 11195183 TI - [Hepatitis C virus infection in patients with end stage renal disease]. PMID- 11195184 TI - [Hyperhomocysteinaemia: physiopathology and medical implications]. AB - Homocysteine is an intermediate aminoacid result of the conversion of methionine to cysteine. Homocystinuria or the hyperhomocysteinaemia are the most frequently related disorders of this aminoacid, being the former an autosomic recessive alteration, whereas the latter is conditioned by multiple factors, being the most important the genetic and nutritional factors. In the last years this alteration has regained special interest because of its increasing role in the thrombotic pathologies and the identification that hyperhomocysteinaemia represents an independent risk factor for the accelerated atherogenesis of multiple diseases. In this review physiopathological aspects and clinical implications of hyperhomocysteinaemia are mentioned as well as its diagnoses and treatment. PMID- 11195185 TI - [In search of prognostic factors in continuous ambulatory peritoneal dialysis]. PMID- 11195186 TI - [Technology's fetishism]. PMID- 11195187 TI - [Importance of risk of contamination from urine samples for diagnosis of urinary tract infection in a third level hospital]. PMID- 11195188 TI - [Central neurogenic hyperventilation associated with a pontine infarction]. AB - Central neurogenic hyperventilation in patients with a normal level of consciousness is uncommon. This condition occurs in bilateral pontine tegmental lesions, particularly tumors such as CNS lymphomas and glioma, as well as traumatic lesions. The physiopathological mechanisms are unknown and no there is no effective treatment for this entity. We report a case of central neurogenic hyperventilation associated to a unilateral basal pontine infarction. PMID- 11195189 TI - [The exercise of a more scientific clinical medicine]. PMID- 11195190 TI - [Is tacit consent more efficient than informed consent in cadaveric organ donation for transplantation?]. PMID- 11195191 TI - [A comparative study of antibacterial activity of ceftibuten, ceftazidime, cefuroxime and ampicillin against clinical isolates]. AB - Ceftibuten is an orally active third generation new cephalosporin. Its antibacterial activity in vitro was tested to many clinical isolates and was compared to the activity of ceftazidime, cefuroxime and ampicillin, by twofold serial dilution method in Muller-Hinton agar--detection of minimum inhibitory concentrations (MIC) and by the disc-diffusion method of Kirby-Bauer. The new cephalosporin demonstrated great activity against the different clinical important strains. Many resistant strains to ampicillin were high susceptible to ceftibuten. The majority of Gram-negative organisms, including Enterobacteriaceae, the respiratory pathogens M.(B.) catarrhalis and H. influenzae are highly susceptible to Ceftibuten, however Pseudomonas, Acinetobacter are resistant. The majority of methicillin-susceptible strains of Staphylococcus are resistant too. New cephallosporin was also active against S. pyogenes (Streptococcus gr. A) and penicillin-susceptible pneumococci, but was inactive against S. agalactiae (Streptococcus gr. B), S. pneumoniae penicillin resistant strains and enterococci, similar to the other cephalosporins. The activity of ceftibuten was higher than that of ampicillin and cefuroxime against beta-lactamases positive strains of H. influenzae and M.(B) catarrhalis, also against tested strains of Enterobacteriaceae. The major priority of the new antibacterial agent over other cephalosporins and ampicillin is its stability to hydrolysis by the main broad-spectrum beta-lactamases producing E. coli and K. pneumoniae sp. PMID- 11195192 TI - [Cytokines and the liver in health and disease]. AB - Cytokines are a group of proteins with autocrine, paracrine and endocrine activities which provide communication among hepatic cells and other cells and tissues of the man. Active in minute quantities, the cytokines activate and regulate homeostasis and cellular repair through effects on cell growth, differentiation and receptor expression and cell-mediated immunity. Cytokines--IL 1, IL-2, IL-6, IL-8 IL-10, IL-12, TNF-alfa, PDGF and others, modulate liver metabolism in health and disease, physiological and pathologic liver functions and the evolution of liver inflammation and injury to hepatic fibrosis and liver cirrhosis. Data concerning the use of a recombinant form of Interleukin-10 and Interleukin-12 in the treatment of chronic liver disease (chronic viral hepatitis, fibrosis, cirrhosis, alcoholic liver disease) and cell-mediated immunity regulation are widely discussed in the review. PMID- 11195193 TI - [Treatment of primary biliary cirrhosis with ursodeoxycholic acid]. AB - This study was undertaken to evaluate the efficacy of ursodeoxycholic acid (UDCA) in the treatment of primary biliary cirrhosis (PBC). Three patients with PBC (stage II) have been treated with UDCA (Ursofalk and Falk Pharma, Freiburg, Germany)--of 10 mg/kg daily dosage in the course of three years. Patients with well-defined PBC underwent complete history, physical examination, liver chemistries, ultrasonography and liver biopsy. Liver chemistries were determined every three months. A control liver biopsy was performed to one of the patient, an year after the beginning of the treatment. UDCA was well tolerated and showed no side effects. The most obvious benefit of UDCA was its favourable effect on serum biochemistries. Its use was associated with the delayed progression of the disease. PMID- 11195194 TI - [Consensus on the treatment of type 2 diabetes mellitus]. AB - The outcome data from the United Kingdom Prospective Diabetes Study (UKPDS) showed that intensive drug treatment of diabetes mellitus-type 2 and the tight control of glycaemia and blood pressure are associated with lower incidence of chronic diabetic complications and mortality. The economical analysis showed out that money invested in the intensive drug treatment of diabetes and arterial hypertension resulted in less expenses for the treatment of diabetic complications. These data are the reason to suggest an algorythm for the treatment of diabetes mellitus type 2. The main aims are to achieve fasting blood glucose < or = 6 mmol/l, 2 hour postprandial glucose < or = 8 mmol/l and glycated haemoglobin (HbA1c) < or = 7.0%. The steps in the treatment include: non pharmacological treatment, monotherapy with an oral drug, combined oral treatment, insulin therapy, combined insulin and an oral drug therapy. The blood pressure control aims to achieve a figure below 140/85 mm Hg, using monotherapy or a combination of antihypertensive drugs from different pharmacological groups. PMID- 11195195 TI - [Nimesulide - a non-steroidal anti-inflammatory drug, a preferential cyclooxygenase-2 inhibitor]. AB - Nimesulide (Aulin) refers to the class of sulphonanilides, which is unique among the non-steroidal antiinflammatory drugs (NSAIDs), being also the first drug on the market of pharmaceuticals, which preferentially inhibits the enzyme cyclooxygenase-2 (COX-2). This enzyme takes part in the synthesis of prostaglandin, which is produced in the course of the cascade of the inflammation process and has relation to the pathogenesis of pain, inflammation and fever, while the COX-1 enzyme forms prostaglandin, which projects the gastro-intestinal mucosis. Many newly found factors, together with the preferential inhibition of COX-2, are also contributing to the therapeutic effects of Nimesulide. The therapeutic concentration of non-combined active substance in blood-circulation reduces the following indicators: the activity of the myeloperoxidase; the release of cytokines; the histamine effects; the synthesis of stromelysin and collagenase, which pull down the proteoglicans and collagen. It is also characteristic of Nimesulide its antioxidant activity and suppression of: the synthesis of superoxidic ions from the neutrophils; also, the synthesis of platelet activating factor. Nimesulide shows good tolerability and is safe with patients having respiratory problems due to treatment with other NSAIDs. PMID- 11195196 TI - [Sodium in clinics and complications of liver cirrhosis]. AB - The changes in sodium homeostasis most frequently are expression of water electrolyte balance disturbances in patients with liver cirrhosis. Hyponatremia of water excess is found in 35% of the patients with cirrhosis and ascites. This disturbance is most frequently connected with raised antidiuretic hormone (vasopressin) secretion and is realized by including of nonosmotic stimulating mechanisms. The vasopressin plays a leading role in pathogenesis of disturbed water metabolism in the liver cirrhosis. Some patients with hepatorenal syndrome are established with highest plasma vasopressin concentrations. Gene expression of the regulation of kidney vasopressin-sensitive water channels (aquaporin-2 proteins) is also raised in the liver cirrhosis. Using in practice vasopressin type 2 (V-2) receptor antagonists gives hopeful results in medical treatment of water-electrolyte disturbances in patients with advanced liver cirrhosis. PMID- 11195198 TI - [Correlation between ventricular potentials and QT dispersion in patients with myocardial infarction]. AB - We investigated QT dispersion (QTcd) and QT apex dispersion (QTad), corrected in relation to heart rate and the presence of ventricular late potentials (VLP) in 27 patients with previous myocardial infarction. VLP were considered positive when two of following tree criteria were satisfied: 1. HF QRS > 114 ms; 2. RMS 40 < 20 microV; 3. LAS > 38 ms. The patients were divided into two groups: group A- with VLP positive, 10 patients and group B--with VLP negative, 17 patients. Group A showed a significantly higher QTcd and QTad than group B (42 +/- 18.1 ms. v/s 24.7 +/- 14.2 ms, p = 0.01 for QTcd and 41 +/- 20.2 ms. v/s 23.5 +/- 11.1 ms, p = 0.007 for QTad). There is also a moderate expressed linear correlation between QTcd and HF QRS (r = 0.459). Our data suggest, that the presence of slowly conducting areas of myocardium, related to positive VLP is associated with expressed inhomogeneity of ventricular repolarisation pi. e. higher QTcd. PMID- 11195199 TI - [Diagnostic algorithm and software for assessment and follow-up of dyspnea]. AB - Breathlessness is a common complaint among patients with lung and heart diseases. It is a complex, multidimensional symptom with descriptive and quantitative aspects. The aim of this study is to constitute a set of questionnaires and scales for adequate assessment of dyspnea and their combination in diagnostic algorithm with various ranges. In order to achieve this goal, we developed a software product DISKO with the following characteristics: Includes the basic instruments for assessing dyspnea in all dimensions--verbal (descriptive) characteristic, everyday activities and exercise dyspnea, as well as its impact on the patients' quality of life. Proposes minimal, optimal and comprehensive algorithm for assessment and follow up of dyspnea. Presents a convenient interface and an ability to configure a flexible data base easy for browsing and handling. Proposed tests and algorithm for dyspnea assessment make it easier for the physician to diagnose and follow up chronically ill patients whose major complaint is dyspnea. The software product DISKO is compliant with the modern requirements for medical software and can be utilized in the process of diagnostic, education and scientific research. PMID- 11195200 TI - Hemorheology in microcirculation: pathological changes. The 7th Tbilisi Symposium. Internet Virtual Symposium. Abstracts. PMID- 11195201 TI - Phylogenetic history of sifakas (Propithecus: lemuriformes) derived from mtDNA sequences. AB - The sifakas (Propithecus) include three species containing up to 10 described subspecies, whose evolutionary relationships remain contentious. In particular, it is unclear whether P. verreauxi deckeni and P.v. coronatus populations are differentiated at the subspecific level. Furthermore, the taxonomic status of the recently discovered P. tattersalli and its phylogenetic position also require further examination. About 2,400 bp of mitochondrial DNA sequence data from part of the COIII gene, together with complete genes for ND3, ND4L, ND4, and five tRNAs, were used to clarify relationships among Propithecus species and subspecies. All analyses group Avahi as the sister group to all sifakas. P. diadema is placed as a sister group to all other Propithecus. Among the remaining sifakas, one subclade is formed by Puv. coquereli and P. tattersalli, while P.v. verreauxi, P.v. deckeni, and P.v. coronatus form the second subclade. All analyses fail to resolve P.vu. coronatus and P.v. deckeni into separate monophyletic lineages. Based on pairwise distance comparisons and tree topology, we conclude that P. tattersalli does not represent a distinct species and that P.v. deckeni and P.v. coronatus do not deserve subspecific rank. On the other hand, our analyses indicate that P.v. coquereli may well represent a separate species. PMID- 11195202 TI - Age differences and developmental trends in alarm peep responses by squirrel monkeys (Saimiri sciureus). AB - Alarm calls can code for different classes of predators or different types of predatory threat. Acoustic information can also encode the urgency of threat through variations in acoustic features within specific alarm call types. Squirrel monkeys (Saimiri sciureus) produce an alarm call, known as the alarm peep, in highly threatening situations. Infant squirrel monkeys appear to have an innate predisposition to respond to alarm peeps but require experience to associate alarm peeps with the appropriate type of predatory threat [Herzog & Hopf, American Journal of Primatology 7:99-106, 1984]. Little is known about age related differences in the type or frequency of response to alarm peeps, or the development of alarm peep response in infants. The purpose of this study was to test experimentally the response strategies of different age classes of squirrel monkey to the playback of alarm peeps that were produced by infants, juveniles, or adults. Results suggest that infants, juveniles, and female subadults respond more frequently to alarm peeps than do adult females. Infant squirrel monkeys showed different behavioral strategies in response to alarm peeps as a function of age. Adult females differentiate between infant and adult alarm peeps by responding more frequently to the alarm peeps of adult females. These data demonstrate that squirrel monkeys use acoustic information to discern when to respond to the alarm peeps from conspecifics, and that infants gradually develop an adult-like response to alarm peeps over the first year of development. PMID- 11195203 TI - Effects of nonmaternal restraint on the vocalizations of infant rhesus monkeys (Macaca mulatta). AB - This study explored the effects of restraint by females other than the mother on the vocalizations of infant rhesus macaques (Macaca mulatta) in a captive social setting. In this species, females are very attracted to young infants and will frequently approach, groom, and hold the infant. Incompetent handling, abusive behavior, or extended periods away from the mother that prevent the infants from nursing represent potentially significant risks for infants. Vocal responses to such risky conditions appear to be the infants' only means to promote a return to their mothers. We examined the association between the severity of the threat posed to the infant and the nature of its vocal response to restraint, and whether the infants' calls influenced the behavior of their mothers or captors. The results suggest that situations posing greater risks for the infants, i.e., longer periods of restraint, were associated with a greater use of noisy screams. Furthermore, mothers' responding was associated with a greater use of noisy screams as well. The mothers' reactions, however, could be described as cautious, and consisted mostly of closer monitoring; such tempered response might be related to the risk of injury to the infant that could result from a more forceful and direct attempt at retrieval. PMID- 11195204 TI - Immunobiology of the reproductive tract in a female baboon. AB - The aim of this study was to assess the suitability of various antihuman antibodies directed against immunocomponent cells to identify components involved in cellular and humoral immune responses in the immune organs of a female baboon, and to use these reagents to analyze the immunobiology of its reproductive tract. A female baboon of reproductive age was euthanized in the luteal phase of the menstrual cycle, and samples of spleen, intestines, tonsil, lymph nodes, Fallopian tube, uterus, cervix, and vagina were removed. Tissues were either fixed in 10% unbuffered formaldehyde, Bouin's fluid, or 95% ethanol containing 5% glacial acetic acid, and embedded in paraffin, or frozen unfixed. Frozen sections were then fixed in 100% acetone. Subsequently, tissue sections were reacted with the following antihuman antibodies directed against CD3, CD45RA, CD45RO, CD4, CD8, CD20, CD68, HLA-DR, CD57, CD103, CD15, and TIA-1: IgA, IgG, IgM, J-chain, secretory component, and neutrophil elastase, using routine immunohistology techniques. Human tissues (spleen, small intestine, lymph node, and tonsil) were used as positive controls. All antihuman antibodies crossreacted with baboon tissues, except neutrophil elastase, CD15, CD45RO, CD57, and CD1A. The distribution of immune cells in the reproductive tract of the female baboon was comparable to that in the human and offers the potential for this primate to be used as a model for the study of human reproductive immunology. PMID- 11195205 TI - [The 75th anniversary of the I. P. Pavlov Institute of Physiology of the Russian Academy of Sciences]. PMID- 11195206 TI - [Specific and nonspecific cortical-subcortical mechanisms of behavior]. AB - The paper presents data on comparative morphological study of afferent connections between the cat, dog, monkey brain basal ganglia with structures of the "motor" and "limbic" systems, neurophysiological data on specifics of involvement of the pre-frontal cortex, amygdala, caudate nucleus and thalamus in the processes of learning, perception and assessment of the stimuli significance, formation of short- and long-term memory's programs, decision making, programming the actions and assessment of the actions being performed, experimental data on the role of glutamatergic, dopaminergic, cholinergic, GABA-ergic systems of the cortex and a number of subcortical structures in the mechanisms of formation and implementation of the food and defence reflexes. PMID- 11195207 TI - [Muscarinic receptors in the neostriatum--participation in the operant behavior regulation in dogs]. AB - Exposure of the dogs to signals, data collection and processing were accomplished using a special PC software. Bilateral microinjections of the muscarinic receptors agonists (oxotremorine) into the neostriatum enhanced the tonic component of instrumental movements, suppressed the phasic component and increased the postural component's amplitude. These changes were much more obvious in microinjections of the non-selective muscarinic receptor agonist carbachol due, probably, to its effect on both the M1 and M4 muscarinic receptors of the neostriatum efferent neurones. PMID- 11195208 TI - [Critical phases of the brain development]. AB - Various effects were shown to act alter the proceeding of histogenetic processes in the embryonic neural tissue. Studies in mice revealed that, depending on the embryogenesis stage when a lack of serotonin occurred, the lack of this monoamine entails either death of the embryo or a teratogenic effect, or underdevelopment of brain structures. In the rat model of a shorten hypoxia, a disorder of neural tissue histogenesis in early stages of development, was found, as well as a reduction of its sensitivity to lack of oxygen by the end of embryogenesis. PMID- 11195209 TI - [Plasticity of the social behavior in Drosophila]. AB - Original data illustrate self-starting classical conditioning to environmental factors in Drosophila, the factors serving as signals of a possible threat from other individuals and blocking initiation of activity. Instrumental conditioning resulting in reduction of an initially high level of activity in the group situation, helps a fly to avoid aggression from other flies and to use the food resources more efficiently. Classical conditioning makes it unnecessary for a fly to learn this instrumental task again and again: being faced with an analogous situation the fly automatically decreases its activity following presentation of the conditioned stimuli or the specific environment. PMID- 11195210 TI - [Corticoliberinergic mechanisms of the neostriatum in the neuroendocrine stress regulation]. AB - Neostriatum and its dopaminergic mechanisms were shown to be involved in mediation of some adaptive effects of the CRH (corticotropin-releasing hormone), both behavioural and endocrine. The data obtained suggest that neostriatum contributes to a coping response by selecting an appropriate behavioural strategy in stressful situation. PMID- 11195211 TI - [Nociceptive system response to repetitive painful stimuli during chronic psychoemotional stress in humans]. AB - Repeated nocigenic stimuli applied to the skin evoked a hyperalgesia in healthy subjects while in patients with neurasthenia which is a natural model of a chronic psychoemotional stress, they evoked a hyperalgesia accompanied by sensitization. The differences in the nociceptive system responses show particularities in reactivity (plasticity) of a wide dynamic range of the spinal neurons under chronic psychoemotional stress that is due to disorders in supraspinal descending modulation system of plasticity in the spinal nociceptive neurons. PMID- 11195213 TI - [The role of the prefrontal and parietal cortex in learning and memory in monkeys]. AB - Removal of the 7th field of parietal cortex and sulcus principalis of prefrontal cortex did not affect learning processes for images with such properties as spatial frequency, orientation, geometrical form, but worsen learning characteristics in visual differentiation of spatial information making the learning processes unstable, longer and below the 85% level. Removal of sulcus principalis also affects learning of differentiation among various colour stimuli. The short-term memory in these monkeys are also much worse than in intact animals. A scheme of learning involving interacting sensory and cognitive processes controlled by motivation system, is proposed. PMID- 11195212 TI - [Effect of the transcranial electrical stimulation of the endorphinergic brain structures on the functional activity of hepatocytes after toxic exposure]. AB - Biochemical events of the rat hepatocytes cytolysis and deterioration of their synthetic activity and detoxification ability, as well as morphological events of lipid degeneration after acute poisoning with dichloretane and CCl4, were significantly reduced by effects of transcranial stimulation (TES). Blockade of the TES effects with naloxone revealed its endorphinergic nature. Combined effects of the TES and Essenciale preparation were lower than separate those of these agents. The TES effects were clinically corroborated in treatment of toxic hepatitis. PMID- 11195214 TI - [Putative molecular mechanism of defensin interaction with the membrane of the sensory neuron]. AB - NP-1 defensin decreased effective charge transfer in the activation gating system of TTX-resistant (slow) sodium channels in a dose-dependent manner. The dissociation constant and Hill coefficient values were KD = 2 pM and X--0.9. Geometry of the NP-1 defensin molecule was built using its primary structure with three S-S briges and fully optimised in the framework of molecular mechanics method. The data obtained explain experimental results of stechiometry 1:1 due to ligand-receptor interaction by the only outward directed carboxyl group of Glu 14 which might form a hydrogen bond with a single binding site of non-identified defensin membrane receptor. PMID- 11195215 TI - [The mismatch negativity as an index of the perception of speech sounds by the human brain]. AB - The present article outlines the contribution of the mismatch negativity (MMN), and its magnetic equivalent MMNm, to our understanding of the perception of speech sounds in the human brain. MMN data indicate that each sound, both speech and non-speech, develops its neural representation corresponding to the percept of this sound in the neurophysiological substrate of auditory sensory memory. The accuracy of this representation, determining the accuracy of the discrimination between different sounds, can be probed with MMN separately for any auditory feature or stimulus type such as phonemes. Furthermore, MMN data show that the perception of phonemes, and probably also of larger linguistic units (syllables and words), is based on language-specific phonetic traces developed in the posterior part of the left-hemisphere auditory cortex. These traces serve as recognition models for the corresponding speech sounds in listening to speech. PMID- 11195216 TI - [Control of the human and animal locomotor activity in the absence of supraspinal effects]. AB - In patients deprived of supraspinal effects, electrical epidural stimulation of the spinal cord's dorsal surface at the level of 2nd lumbar segment induces step like movements accompanied by respective electromyographic activity of the leg's muscles. Triggering of the step-like movements occurs at certain parameters of the stimulation. The data obtained suggest that human spinal cord has networks of interneurons-generators of the step-like movements. A leading role of the spinal cord's propriospinal system in activation of spinal generators of stepping under epidural influences was shown in cats. PMID- 11195217 TI - [Visceral field of the rat insular cortex]. AB - Structural-functional organisation of the cortical insular area relating to processes of the visceral functions control, was analysed. Representation of gastrointestinal, respiratory, and cardiovascular systems in the area, is given. Sites of respective neuronal groups and specifics of their spatial organisation within the area, were found. The data obtained suggest a scheme of the rat insular cortex's visceral field. PMID- 11195218 TI - [Effect of hypotension on the arterial system responsiveness]. AB - The correlation analysis revealed no correlation within the range 110 to 80 mm Hg further transforming into a direct (within the range lower than 80 mm Hg) dependence of the pressure responses to mesatone on the reduction of initial mean arterial pressure under orthostatic hypotension in anaesthetised rats. Under paraverine hypotension a reverse correlation within the range 110-80 mm Hg transforming into a direct dependence (within the range lower than 80 mm Hg) of the responses to mesatone were observed. The dependence of cardiac shifts to mesatone on the initial arterial pressure was not occurred. The mechanisms of dependence of the systemic vascular responses on initial tone of arterial vessels, are discussed. PMID- 11195219 TI - [Metabolic/nutrition programming of the enzyme system in the offspring small intestine]. AB - Protein deficiency in female rats diet during pregnancy and lactation resulted in changes of the intestine enzymes activity in posterity in early and late periods of ontogenesis. In the former period, deceleration of sucrase induction, acceleration of lactase suppression and maltase induction, and an earlier occurrence of the adult-type distribution of the intestine alkaline phosphatase, were found. At 2 to 4-month age a reduction of the latter enzyme activity was revealed in the doudenum, jejunum and ileum. The changes in the intestine enzymes activities led to a disorder in intermediary metabolism and to occurrence of "risk diseases". PMID- 11195220 TI - [The role of histamine in vagal and gastrin effects on the secretory function of the rat stomach]. AB - In lumen-perfused stomachs of anaesthetized rat, acid and bicarbonate types of secretion were estimated on the basis of pH/PCO2 measurements. The data obtained reveal that, in anaesthetised rats, pentagastrin and cholinergic input affect acid secretion mainly indirectly via histamine release. Vagal effects on pepsinogen output are mediated partially via indirect histamine pathways. The direct action of pentagastrin, however, predominates. Bicarbonate production is subjected to cholinergic control alone. PMID- 11195221 TI - [The role of endogenous glucocorticoids in maintenance of the gastric mucosa integrity]. AB - Effect of glucocorticoid deficiency on susceptibility to gastric mucosal injury by non-steroid anti-inflammatory drugs (NSAID) was studied in rats. The corticosterone production was inhibited by a single large dose of cortisol as well as by an adrenalectomy. The drop in the corticosterone production prompted gastric erosions induced by the NSAID. Replacing corticosterone prevented the effects of cortisol pretreatment of adrenalectomy on NSAID-induced gastric erosions. The data obtained reveal a gastroprotective effect of endogenous glucocorticoids. PMID- 11195222 TI - [History of the unique museum--apartment of Ivan Petrovich Pavlov in the I. P. Pavlov Institute of Physiology of the Russian Academy of Sciences]. PMID- 11195224 TI - Quantifying infant respiratory variability: how to capture complexity. PMID- 11195223 TI - Overcoming surfactant inhibition with polymers. AB - Inhibition of the function of pulmonary surfactant in the alveolar space is an important element of the pathophysiology of many lung diseases, including meconium aspiration syndrome, pneumonia and acute respiratory distress syndrome. The known mechanisms by which surfactant dysfunction occurs are (a) competitive inhibition of phospholipid entry into the surface monolayer (e.g. by plasma proteins), and (b) infiltration and destabilization of the surface film by extraneous lipids (e.g. meconium-derived free fatty acids). Recent data suggest that addition of non-ionic polymers such as dextran and polyethylene glycol to surfactant mixtures may significantly improve resistance to inhibition. Polymers have been found to neutralize the effects of several different inhibitors, and can produce near-complete restoration of surfactant function. The anti-inhibitory properties of polymers, and their possible role as an adjunct to surfactant therapy, deserve further exploration. PMID- 11195225 TI - Familial aggregation and pain theory relating to recurrent pain experiences in children. PMID- 11195226 TI - What are the most effective means of promoting exclusive breastfeeding? PMID- 11195227 TI - Unnecessary water supplementation for babies: grandmothers blame clinics. AB - This study was designed to obtain policy-and programme-relevant data on exclusive breastfeeding in Lesotho at a time when global recommendations for exclusive breastfeeding were new. During both phases of field research, conducted in 1991 and 1992, qualitative information was obtained through focus groups and individual interviews with mothers, grandmothers and nurses. This was complemented during the second phase with quantitative data collected through a clinic-based survey of mothers. The qualitative and the quantitative findings consistently converged, illustrating a culture of infant feeding in which breastfeeding was central, but exclusive breastfeeding was an unknown concept and not practised. Grandmothers seemed to be more in tune with the ideal of exclusive breastfeeding as they had given their young infants thin gruel only occasionally. Contemporary mothers, in contrast, were regularly giving their young infants water. Mothers and grandmothers frequently cited nurses as the source of advice for giving water. Grandmothers were adamant in pointing out that they had never given water to their own young infants and asserted that they avoided giving it to their grandchildren as they considered it unnecessary and harmful. According to the grandmothers, water supplementation was a new practice that had been introduced through the clinics. CONCLUSION: Efforts to discourage water supplementation and encourage exclusive breastfeeding in this setting need to be directed both at mothers and health providers. PMID- 11195228 TI - Residual pulmonary hypertension in children after treatment with inhaled nitric oxide: a follow-up study regarding cardiopulmonary and neurological symptoms. AB - Inhaled nitric oxide is a potent vasodilator in acute severe pulmonary hypertension and is increasingly used as rescue treatment in intensive care algorithms aiming at reducing severe hypoxaemia in neonates and children. Although the immediate effects may seem impressive, long-term outcome regarding residual pulmonary hypertension and other sequelae has been studied in only a very few patients. The aim of the present study was to evaluate residual pulmonary hypertension, cardiopulmonary or neurological symptoms in children after treatment with inhaled nitric oxide in severely hypoxaemic and/or pulmonary hypertensive mechanically ventilated children. The study was performed in four paediatric intensive care units in university hospitals in Sweden, Norway and Australia. Patients who had received inhaled nitric oxide as part of their intensive care treatment for severe hypoxaemia and/or pulmonary hypertension, and in whom 6 mo had elapsed since treatment, were included for evaluation. Thus 36 paediatric or neonatal patients were examined for circulatory, respiratory or neurological disorders with clinical examination, echocardiography, chest X-ray and a capillary blood sample. Four patients with congenital heart disease had residual pulmonary hypertension. Nine patients were receiving bronchodilators. Sixteen patients had minor (n = 15) or moderate (n = 1) changes on a chest X-ray. One patient had a possible delay in psychomotor development. CONCLUSIONS: In spite of the severity of their primary illness, we found that the overwhelming majority of the surviving children were asymptomatic and doing well. The few residual circulatory and respiratory symptoms could be related to the initial condition. PMID- 11195229 TI - A study of breathing pattern and ventilation in newborn infants and adult subjects. AB - Experimentally modified breathing pattern in human subjects, by varying the inspired gas mixture or administering different neuromodulators, has been studied extensively in the past, yet unmodified breathing has not. Moreover, most data refer to infants during sleep and adults during wakefulness. We studied the baseline breathing pattern of preterm infants [n = 10; GA 30 (27-34) wk (median, range)]; term infants [n = 10; GA 40 (39-41) wk)], and adult subjects [n = 10; age 31 (17-48) y)] during quiet sleep. A flow-through system was used to measure ventilation. We found: (i) instantaneous ventilation was 0.273+/-0.006, 0.200+/ 0.003, and 0.135+/-0.002 L x min(-1) x kg(-1) in preterm, term infants, and adult subjects; the coefficients of variation were 39%, 25%, and 14% (p < 0.01). The greater coefficient of variation in neonates compared to adults related to increased variability in Vt (39% and 25% in preterm and term infants vs 14% in adults; p < 0.01) and f (39% and 22% vs 9%; p < 0.01). The major determinant of frequency in preterm infants was Te (81% variability), Ti varying less (25% variability); (ii) V(T)/Ti decreased and Ti/Ttot increased with age; (iii) the higher breath-to-breath variability in preterm infants was associated with larger changes in alveolar PCO2 and a larger variability in O2 saturation than later in life. PMID- 11195230 TI - HLA-DQA1*05-DQB1*0201 positivity predisposes to coeliac disease in Czech diabetic children. AB - The aims of this study were to estimate the prevalence of coeliac disease (CD) in Czech children with insulin dependent diabetes mellitus (IDDM), and to determine the contribution of HLA-DQA1 and DQB1 to CD susceptibility among diabetic children. We screened 345 children with IDDM (186 boys and 159 girls, aged 0 to 18 y) for coeliac disease using the IgA endomysial antibodies (EMA) test. In all EMA-positive children, small bowel biopsy was performed to confirm CD. To determine the role of the HLA-DQA1*05-DQB1*0201 (DQ2) and the DQA1*03-DQB1*0302 (DQ8) molecules in CD susceptibility among diabetic children, the HLA-DQA1-DQB1 was genotyped in all EMA-positive, and in 186 of EMA-negative diabetic patients. EMA positivity was found in 15/345 (4.3%) diabetic children. The diagnosis of CD was established in 14/345 (4.1%) children based on a bioptic finding of villous atrophy, while the remaining EMA-positive patient had a normal bioptic finding, being diagnosed as a potential CD. The HLA DQA1*05-DQB1*0201 (DQ2) molecule conferred a significant risk of CD among diabetic children (odds ratio = 4.1, CI 95% 1.1-15), being found more frequently in diabetic children with CD (80%) than in diabetic children without CD (49%). CONCLUSION: The high prevalence of CD (4.1%) found in Czech children with IDDM emphasizes the need for their regular screening. We suggest that this CD screening protocol may be individualized according to the DQA1*05-DQB1*0201 positivity. PMID- 11195231 TI - Elevated serum creatinine levels in infants with congenital hypothyroidism: reflection of decreased renal function? AB - The effects of hypothyroid status on renal function have been poorly studied in children. We assessed the renal function of hypothyroid infants detected during neonatal mass screening for congenital hypothyroidism (CH). Eighty hypothyroid infants and 20 age-matched normal infants for controls were enrolled. The 80 patients, aged 1 mo, were divided into two groups based on the initial thyroid stimulating hormone (TSH) and free thyroxine (FT4) values: a mild-moderately hypothyroid (MHT) group (n = 64, 31M and 33F) and a severely hypothyroid (SHT) group (n = 16, 3M and 13F). Serum creatinine (SCr), TSH, FT4 and other chemicals were compared before and 2 mo after L-thyroxine (LT4) substitution therapy. The following results were obtained: SCr levels were significantly higher in the SHT group (33.2+/-10.0 micromol/L, p < 0.001) compared with the MHT group (20.6+/-6.4 micromol/L) and normal control group (21.0+/-4.4 micromol/L). Two months after the LT4 replacement therapy, the elevated SCr levels in the SHT group decreased by 41.3% to the level (19.5+/-6.0 micromol/L) very close to that in the MHT group (18.8+/-5.1 micromol/L). No significant differences were noted among BUN levels in the three groups. Although serum creatinine kinase levels were significantly higher in the SHT group (230.3+/-102.3 U/L, p < 0.001) than in the MHT group (121.1+/-60.8 U/L), rhabdomyolysis was not considered to be responsible for the impaired renal function. CONCLUSION: From these results we conclude that serum creatinine levels are elevated in congenitally hypothyroid infants. This is a reversible change with thyroid hormone replacement therapy. The possibility of impaired renal functions should be kept in mind when treating hypothyroid infants. PMID- 11195232 TI - A multicenter collaborative study on the risk factors of cardiac sequelae due to Kawasaki disease: a one-year follow-up study. AB - OBJECTIVE: To measure the prevalence of cardiac sequelae 1 y after the onset of Kawasaki disease and determine the risk factors associated with these cardiac sequelae. MATERIAL AND METHODS: 1594 patients who initially visited one of the 87 target hospitals in 1996 for Kawasaki disease participated. Selection of the target hospitals was based on a nationwide survey. The patients were followed-up and information concerning cardiac sequelae occurring within 1 y of onset was obtained by mail survey. RESULTS: The prevalence of cardiac sequelae 1 mo after onset was 10.2% and decreased to 4.2% in 1 y. The prevalence was higher among males than females and higher in patients less than 1 y and 5 ys or older than in 1-4 year-olds. Of the patients with cardiac sequelae at 1 mo, the sequelae disappeared in 60.7% after 1 y. Analysis revealed low serum albumin as a risk factor related to the occurrence of cardiac sequelae 1 y after onset. Of the 1594 patients, 10 had giant anuerysms and 3 had a fatal outcome. CONCLUSIONS: Approximately 60% of cardiac sequelae due to Kawasaki disease that developed within 1 mo after onset disappeared in 1 y. The odds ratio was significantly higher among patients with a low serum albumin level 1 y after onset. PMID- 11195233 TI - Dextran reduces surfactant inhibition by meconium. AB - We have previously shown that an addition of dextran to surfactant increases resistance to inactivation by albumin. The present study was designed to investigate whether dextran has a protective effect against inactivation of surfactant by meconium. The dynamic surface properties of various mixtures of modified natural surfactant (Curosurf), meconium and dextran were evaluated with the pulsating bubble technique. In the absence of meconium, an addition of dextran at 10 mg ml(-1) significantly shortened the surface adsorption time of Curosurf suspended in normal saline at a concentration of 5 mg ml(-1) from 1.6+/ 1.3 (mean +/- SD) sec to 0.4+/-0.4 sec (p < 0.05). Meconium at 5 mg ml(-1) increased the mean minimum surface tension (gammamin) after 3 min of pulsation from 2.1 mN m(-1) to 24 mN m(-1) (p < 0.05). An addition of dextran at 5 and 10 mg ml(-1) to the meconium-surfactant mixture significantly reduced the gammamin to 6.4+/-4.5 mN m(-1) and 2.6+/-5.6 mN m(-1), respectively (p < 0.05 vs dextran 0 mg ml(-1)). Meconium also increased the maximum surface tension (gammamax) of Curosurf from about 33 mN m(-1) to 53 mN m(-1). An addition of dextran at 5 and 10 mg ml(-1) to the meconium-surfactant mixture reduced the gammamax to 41 and 39 mN m(-1), respectively (p < 0.05 vs dextran 0 mg ml(-1)). There were significant negative correlations between dextran concentration and both gammamin and gammamax. We conclude that dextran reduces surfactant inhibition by meconium in a dose-dependent manner. PMID- 11195234 TI - Effect of low-dose cisapride on gastric emptying and QTc interval in preterm infants. AB - The aim of the study was a prospective survey of the effects of low-dose cisapride on gastric emptying and QTc interval in very low birthweight infants. Twenty low birthweight infants were studied: mean (SD) gestation 30.5 (2.2) wk; birthweight 1320 (150)g. Gastric emptying was assessed ultrasonically in 15 of these infants, in a randomized blind crossover study, following 24-h low-dose oral cisapride administration (0.1 mg/kg given 8 hourly), or placebo. The QTc interval was also determined in all 20 infants following a 7-d course of cisapride or placebo. CONCLUSIONS: Cisapride significantly shortened both gastric emptying time and QTc interval (p < 0.05) compared to placebo. All infants completed the study without any apparent adverse effects. In conclusion, low-dose cisapride administration significantly improves gastric emptying without increasing the QTc interval. PMID- 11195235 TI - Budesonide delivered by dosimetric jet nebulization to preterm very low birthweight infants at high risk for development of chronic lung disease. AB - We investigated the effect of an aerosolized corticosteroid (budesonide) on the oxygen requirement of infants at high risk for developing chronic lung disease (CLD) in a randomized, double-blind study. The study objective was to attain a 30% decrease in FiO2 levels in the budesonide treatment group after 14 d of therapy. Thirty very low birthweight (VLBW) infants (median (range)) gestational age 26 wk (23-29) and birthweight 805 g (525-1227) were randomized. Inclusion criteria were mechanical ventilation on day 6 of life, or if extubated on nasal continuous positive airway pressure with FiO2 > or = 0.3. The budesonide (Pulmicort) dose was 500 microg bid, or placebo. The aerosol was delivered with a dosimetric jet nebulizer, with variable inspiratory time and breath sensitivity. Inhalations were started on day 7 of life. Twenty-seven patients completed the study. A significant lowering of the FiO2 levels at 21 d of life was not detected. Infants who received budesonide were more often extubated during the study period (7/8 vs 2/9) and had a greater relative change from baseline in their oxygenation index (budesonide decreased 26% vs placebo increased 60%). Subsequent use of intravenous dexamethasone or inhaled budesonide in the treatment group was significantly less. All patients required O2 supplementation on day 28 of life. At 36 wk postconceptual age, 61% of infants in the budesonide group needed supplemental O2 as opposed to 79% in the placebo group. No side effects on growth or adrenal function were observed. CONCLUSION: We conclude that inhaled budesonide aerosol via dosimetric jet nebulizer started on day 7 of life for infants at high risk for developing CLD decreases the need for mechanical ventilation similar to intravenous dexamethasone, but without significant side effects. PMID- 11195236 TI - Early motor development of premature infants with birthweight less than 2000 grams. AB - The aim was to assess motor function during infancy in order to predict later function, mainly cerebral palsy. The neuromotor development of a population-based cohort of 209 of 236 (89%) survivors with a birthweight less than 2000 g was assessed using the Infant Neurological International Battery (INFANIB) and detailed neurological assessment. The infants were classified as being normal, dystonic, hypotonic or having suspected cerebral palsy (CP) at 4, 7, 13 and 18 mo corrected age if birthweight was less than 1500 g (n = 119) and at 7 and 13 mo if birthweight was 1500-1999 g (n = 90). Those with dystonia or suspected CP were followed until diagnosed as normal or as having CP after at least 36 mo of age. Fourteen (7%) finally developed CP. Motor function at 4 mo was inaccurate in predicting function at 7 mo and later. All who were normal at 7 mo remained normal in the follow-up period. Eight of 65 who were dystonic at 7 mo developed suspected CP, and three judged as suspected CP were eventually normal. The 14 who developed CP were judged as suspected CP (n = 5) or dystonic (n = 8) and one as hypotonic at 7 mo of age. CONCLUSIONS: The specificity of motor evaluation at 7 mo corrected age regarding CP is unsatisfactory, since dystonia at this age is most often transient. A normal neuromotor assessment at 7 mo is highly predictive of subsequent normal motor function. PMID- 11195237 TI - Influence of the initial management regimen and family social situation on glycemic control and medical care in children with type I diabetes mellitus. AB - It is well known that social family factors are of importance in diabetes care, but it is not clear whether the initial management regimen can buffer these factors. In a prospective, randomized intervention study, 36 children with diabetes mellitus (type I) were followed, the aim being to study if a family psychosocial intervention at diagnosis could improve glycemic control and minimize hospital admissions. The control group was treated initially in a hospital ward, while the study group received problem-based learning and family therapeutic and social support in an out-hospital training apartment. A number of family social variables were evaluated at the time of diagnosis and 6, 12 and 24 mo later. Family function was assessed using the self-estimated Family Climate Test at these same time-points. HbAlc values and information concerning in- and out-hospital visits to the pediatric clinic were collected for the 5-y period following diagnosis. We found no association between the offered management regimen and glycemic control or rate of readmission. In the study group only, both parents reported a significant improvement of the family climate. An increased risk for poor glycemic control was recorded in children living in one parent families (p = 0.03) or in families where the father had a low level of education (p = 0.04). Younger age (p = 0.05), a single-parent family (p = 0.05) and poor glycemic control (p = 0.02) were associated with more days of rehospitalization. The rate of divorce in the whole group was at least as high as in the normal population but, surprisingly, maternal dysfunction was associated with lower HbAlc value. The conclusion is that even with an initial management regimen designed to offer a family-individual care regimen based on accurate estimation of the psychological and pedagogical needs, the social family background is a most important factor for the glycemic control and need for readmission. PMID- 11195238 TI - Parents' perception of mental development and behavioural problems in 8 to 9-year old children. AB - A slow maturational rate may be an underlying antecedent of a psychiatric disorder. If this is correct, differences in behavioural problems could be related to the maturity level in children of the same chronological age. The aim of the study was to compare the parents' perceptions and assessments of their children's maturational status and behavioural problems. A population based on a nationwide sample from the Swedish twin-register of 8 to 9-y-old children (n = 1079) was used. The parents completed a questionnaire including their views on their child's maturity level, the Swedish version of the Child Behaviour Checklist (CBCL) and an Attention Deficit Hyperactivity Disorder (ADHD) checklist based on the DSM-III-R criteria. Multivariate analyses showed a statistically significant relationship between immaturity reported by the parents and several behavioural problems reported on the CBCL: somatic complaints, anxious and depressed, social problems, thought problems, attention problems, behaviour problems and aggressive behaviour. There was also a statistically significant relationship between the maturity factor and the CBCL grouping of syndromes (internalizing, externalizing, total behaviour problems score) as well as between the maturity factor and ADHD. CONCLUSION: We conclude that at least from the parents' point of view the behaviour problems in their children may be related to maturity. PMID- 11195239 TI - Children of mothers abusing amphetamine: head circumference during infancy and psychosocial development until 14 years of age. AB - OBJECTIVE: To study the relationship between head circumference (HC) at birth (HO) and at 1 y of age (HI) and later outcome variables in children exposed to amphetamine during fetal life through maternal drug abuse. METHOD: Prospective longitudinal study of 65 children born to women abusing amphetamine. Potential bivariate and partial correlations between HC and outcome variables at 4, 8 and 14 y of age were studied. In multivariate analyses on outcome variables, HC, maternal and perinatal factors were used as predictors. Analyses were performed for all children and separately for boys and girls. RESULTS: Head circumference at birth and 1 y of age were significant predictors for the level of achievement in Swedish language at 14 y. Head circumference at birth was a significant predictor for grades in mathematics in boys. Combined assessment of psychomotor development and psychosocial adjustment at 4 and 8 y correlated with HI in girls. CONCLUSION: Head circumference at birth and at 1 y of age correlated with school achievement at 14 y. HI also correlated with adjustment at 4 and 8 y in girls. A difference in vulnerability between girls and boys is important and should be considered in longitudinal studies of risk cohorts. PMID- 11195240 TI - Recurrent pain symptoms in children and parents. AB - Recurrent pain in five different areas (stomach, arms & legs, head, back and neck & shoulders) in a population of 348 school children and their parents has been investigated. The study presented here is restricted to 229 mother-father-child trios. Forty-four percent of the children reported pain in at least one area compared to 60% of the mothers and 51% of the fathers. Headache and pains in arms and legs were most common in boys. The most frequent pain sites for girls were head and back. Overall, girls complained more than boys. No significant associations between complaints in parents and their children were demonstrated, analysed by logistic regression analysis. Furthermore, there was no significant association between the reported pain in the mother and father. CONCLUSION: Children's pain did not associate with parental pain in this study. The results do not support previous hypotheses that recurrent pain clusters in families. PMID- 11195241 TI - Diagnosis and prognosis of wheezing disorders in young children in the city of Sao Paulo, Southeast Brazil. AB - Three-hundred-and-ninety-seven children aged 2-59 mo presenting to the paediatric emergency departments of five public hospitals in Sao Paulo, Brazil, with an acute episode of lower respiratory disease were examined. The children were classified into the following diagnostic categories: acute bronchitis, acute bronchiolitis, pneumonia, asthma, post-bronchiolitis wheezing and wheezing of uncertain aetiology. Three years after the initial study, the homes of the children diagnosed as asthmatic or as having wheezing of uncertain aetiology were visited to collect information on subsequent episodes of lower respiratory disease. This paper reports the proportional incidence of different categories of lower respiratory disease and the results of an analysis to investigate clinical features that might distinguish wheezing children between those with asthma and those with an infectious disease. The predictions made for children with wheezing of uncertain aetiology were then compared with the follow-up data. Recurrent wheezing disorders (asthma, post-bronchiolitis wheezing) were common in the study sample (47% of children). Thirty-six percent of children with an initial diagnosis of wheezing of uncertain aetiology were diagnosed as asthmatic by another doctor over the next 3 y. We were unable to identify any clinical features that were useful in identifying those children likely to be diagnosed subsequently as asthmatic. CONCLUSIONS: The use of a diagnostic category similar to that which we have called "wheezing of uncertain aetiology" might help to alert physicians early to the possibility of asthma without interfering in the management of the illness. Such a classification might also be useful in epidemiological investigations of the aetiology of lower respiratory diseases. PMID- 11195242 TI - Does maternal or paternal heredity affect carotid atherosclerosis in children with familial hypercholesterolaemia? AB - Maternal hypercholesterolaemia has recently been shown to increase the number of fatty streaks in the foetal aorta, as well as subsequent progression of fatty streaks to more advanced lesions. We compared carotid intima-media thickness by B mode ultrasonography in children who inherited familial hypercholesterolaemia from their mothers or fathers, hypothesizing that children whose mothers were hypercholesterolaemic during pregnancy had increased atherogenesis compared with children whose mothers did not have familial hypercholesterolaemia. We found that carotid intima-media thickness and prevalence of plaque did not differ between children with familial hypercholesterolaemia who inherited FH maternally or paternally. PMID- 11195243 TI - Clinical features, laboratory findings and differential diagnosis of benign acute childhood myositis. AB - We report clinical and laboratory data from 32 children with benign acute childhood myositis (BACM), children who presented with calf tenderness and gait abnormality. Laboratory evidence of a viral infection was evident in 23 patients, while serum creatine phosphokinase was uniformly increased (558 to 6800 U/L). Twenty-five patients (78.1%) were given a diagnosis other than BACM by their general practitioner or paediatrician. All patients made a rapid recovery within one week. We conclude that BACM should be encountered among the main causes of sudden-onset gait abnormality in young children. PMID- 11195244 TI - Sternal tuberculosis in a 9-month-old infant after BCG vaccination. AB - Tuberculosis osteitis is mainly observed as a late complication of the pulmonary infection. We describe a 9-mo-old Japanese infant who became infected with Mycobacterium tuberculosis even after receiving Bacillus Calmette-Guerin (BCG) vaccination at 3 mo of age. This is the first report that the sternum is the localization for tuberculous osteitis in infants. He developed a localized tumor in the sternum without any respiratory symptom. Mycobacterium tuberculosis complex was detected by means of nucleic acid amplification test. Gastric aspirates also yielded Mycobacterium tuberculosis. The source of the infection was unclear. CONCLUSION: Tuberculous osteitis should be excluded in infants with undiagnosed bone lesions, even if they have been vaccinated with BCG. PMID- 11195245 TI - Acyclovir-resistant varicella infection with atypical lesions in a non-HIV leukemic infant. AB - An HIV-negative infant presented with VZV primary infection during the maintenance therapy for megakaryoblastic leukaemia. The lesions were initially vesicular and necrotic but became verrucous and hyperkeratotic. A clinical resistance to acyclovir was suspected and confirmed by histologic and virologic studies. The patient was successfully treated by foscarnet. CONCLUSION: resistance of VZV to acyclovir may occur after a short treatment in a non-AIDS patient. PMID- 11195246 TI - Continuous veno-venous haemodiafiltration in an infant with a stage ivs neuroblastoma and acute renal failure. PMID- 11195247 TI - Coronary revascularization in seven-year-old boy with homozygous familial hypercholesterolaemia. PMID- 11195248 TI - Retrospective neuropsychological evaluation of 18 Romanian subjects with hyperphenylalaninaemia. PMID- 11195249 TI - Increase of serum prolactin during combined high-dose estrogen and progestin treatment in girls with constitutional tall stature. PMID- 11195250 TI - Urinary tract dysfunction in children with cerebral palsy. PMID- 11195251 TI - Preventing the transmission of bloodborne pathogens in health care and public service settings. PMID- 11195252 TI - An integrated protocol to manage health care workers exposed to bloodborne pathogens. PMID- 11195253 TI - Canadian contingency plan for viral hemorrhagic fevers and other related diseases. PMID- 11195254 TI - Guidelines for preventing the transmission of tuberculosis in Canadian Health Care Facilities and other institutional settings. PMID- 11195255 TI - Does risperidone have a place in the treatment of nonschizophrenic patients? AB - There is a now a substantial body of evidence that suggests the new antipsychotic agent, risperidone, may be safe and effective for treating psychotic, affective or behavioural symptoms associated with various disorders other than schizophrenia, schizophreniform disorder or schizo-affective disorder. These conditions include bipolar disorder, obsessive-compulsive disorder, Tourette's syndrome, dementia, Lewy body disease, mental retardation, Parkinson's disease, idiopathic segmental dystonia and organic catatonia. Although much of the data is anecdotal or in the form of open studies, there is now emerging a small number of well controlled investigations supporting efficacy for mania, dementia, behavioural disturbance in mental retardation and conduct disorder. Conventional antipsychotics have long been used, either in a primary capacity or as an adjunct to treat these disorders; however, they have limited benefit, pose significant risks of extrapyramidal side-effects, and may cause the potentially life threatening neuroleptic malignant syndrome. In contrast, risperidone at the recommended low doses may be efficacious and pose reduced risk of motor side effects. This article reviews the evidence that risperidone may be an effective new treatment for disorders other than schizophrenia. PMID- 11195256 TI - An open trial of citalopram in adolescents with post-traumatic stress disorder. AB - In this preliminary, 12-week open-label study, eight adolescents with moderate to severe post-traumatic stress disorder (PTSD) were treated with citalopram (the most selective of the selective serotonin reuptake inhibitors) in a fixed daily dose of 20 mg, and rated at 2-week intervals. The Clinician-Administered PTSD Scale (Child and Adolescent Version) was the primary measure used to assess treatment outcome. Core PTSD symptoms (re-experiencing, avoidance, and hyperarousal symptoms) showed statistically significant improvement at week 12 on the Clinician-Administered PTSD Scale (Child and Adolescent Version) (CAPS-CA), with a 38% reduction in total CAPS scores between baseline and endpoint. Citalopram failed to effect improvement on self-reported depressive symptoms. All seven adolescent completers were rated as much improved or very much improved on Clinical Global Impression Improvement scores. Citalopram was well-tolerated overall with reported adverse experiences being relatively benign. However, larger, controlled trials are needed to consolidate these preliminary results. PMID- 11195257 TI - Efficacy and tolerability of moclobemide in bulimia nervosa: a placebo-controlled trial. AB - A 6-week double-blind placebo-controlled trial was carried out to examine the efficacy and tolerability of moclobemide, a monoamine oxidase type A selective and reversible inhibitor, in the treatment of bulimia nervosa. Patients were admitted to the study even if they were unable to adhere to a tyramine-free diet. Fifty-two normal-weight women (age range 18-40 years) suffering from bulimia nervosa (DSM-IV criteria) completed the trial. Particular emphasis was placed on evaluating the incidence of hypertension and other side-effects in chronically treated patients. At the usual antidepressant dose of 600 mg, moclobemide was not significantly superior to placebo in the reducing the weekly number of binge eating episodes or in improving several measures of eating attitudes and behaviour (BITE, EDI, TFEQ) in normal-weight bulimia nervosa. The dropout rate was relatively low (29%), and the side-effects were limited and equally distributed between the two treatment groups. No patient experienced a hypertensive crisis during the study and no serious side-effect was detected. The study indicates that moclobemide 600 mg pro die is not efficacious in bulimia nervosa, but it can be safely administered, even to young subjects, at a very high risk of consuming large amounts of tyramine-rich foods without dietary restrictions. PMID- 11195258 TI - Relapses after discontinuation of drug associated with increased resistance to treatment in obsessive-compulsive disorder. AB - The aim of the present study was to determine whether obsessive-compulsive disorder (OCD) patients whose symptoms recur after drug discontinuation respond again when the same drug at the same daily dosage is reinstituted. Eighty-one patients who were responders to a previous 6-month, open-label, noncomparative, acute treatment phase with fixed doses of selective reuptake inhibitors (SRIs) and who relapsed within 6 months of drug discontinuation had the drug to which they responded in the acute phase reinstated at the same daily dose. The reinstitution trial lasted 24 weeks with monthly evaluations (Yale-Brown Obsessive-Compulsive Scale and Clinical Global Improvement). Data obtained in the reinstitution phase were analysed using Pearson's chi-squared test or Fisher's exact test when appropriate. The cumulative percentages of patients who responded in the second trial were compared to those of patients who responded in the acute treatment phase (for each treatment and for all SRIs together) across all evaluation times. When considering all patients together, a lower percentage of responders resulted when SRIs were reinstated: the difference in the cumulative percentage of responders appeared at month 4 and increased at months 5 and 6 (Pearson chi-squared, P = 0.028, P = 0.009 and P < 0.001, respectively). When considering the patients separately according to the SRI used, no differences in the percentages of responders were found at any time. Our results indicate that patients whose symptoms recur after drug discontinuation respond again when the same drug used previously (at the same dosage used in the acute phase) is reinstated, but at a lower degree with respect to the acute treatment. Findings from our study, together with literature data indicating high relapse rates when discontinuing the treatment after the acute phase, support the idea of continuing the treatment in OCD over the long term. PMID- 11195260 TI - Depression in the community: results of the first Italian survey. AB - The 6-month prevalence of depression in the Italian community was evaluated by means of the modified-Mini-International-Neuropsychiatric Interview (MINI) administered with a computer-prompted interview to a representative panel of 3550 individuals. Major depression and minor depression accounted for 8.0% and 2.9% of the cases, respectively. Major depression was 1.3 times as prevalent in females (compared to males), while minor depression was 1.6 times as prevalent in males. Prevalence of major depression was maximal (11.9%) in subjects aged 30-49 years, and minimal (4.1%) in subjects aged 60 years or older. These results confirm prevalence figures for depression in the community reported with the modified MINI for other European countries, and support the use of telematic data acquisition for health-related general population surveys. PMID- 11195259 TI - Hyperactivity in the hypothalamic-pituitary-adrenal axis in demented patients with delirium. AB - Occurrence of delirium is known to be related to, among other things, organic brain disorder, somatic disease and old age. It has been hypothesized that delirium is also associated with stress. Disturbances of the hypothalamic pituitary-adrenal (HPA) system have been found in delirious patients in various studies. The aim of the present study was to determine the activity in the HPA axis in demented patients to ascertain whether the stress regulating system was more disturbed in patients with delirium than in those without delirium. Demented inpatients with no acute medical illness were included in the study. Basal cortisol levels in serum were measured and dexamethasone suppression test (DST) was performed. The most important finding of the study was a strong relationship between delirium and DST pathology irrespective of age and severity of dementia. It is suggested that certain demented individuals have an impaired HPA system and a low delirium threshold and respond to stress with delirium. PMID- 11195261 TI - Olanzapine-induced leukopenia with human leukocyte antigen profiling. AB - Olanzapine is an atypical antipsychotic medication frequently used in the management of psychotic states. While it has proved to be safe compared to clozapine with regard to haematotoxicity, because it has only been available for a few years, full documentation of its haematological side-effects remains incomplete. We report a case of olanzapine-induced leukopenia with associated neutropenia. Since clozapine-induced haematotoxicity has been associated with characteristic human leukocyte antigen (HLA) groups, HLA typing was determined in this patient. Following failure with typical antipsychotic medication, the patient received 10 mg/day of olanzapine. Three weeks later, he developed fever and a significant decrease in leukocyte count. Olanzapine was immediately discontinued. HLA typing was determined. The white cell count returned to normal and the fever, most probably secondary to the low white cell count, subsided with antibiotic treatment. HLA typing results were: A1 24, B7, B35, DRB1*15, DRB1*11, DRB3*01-03, DRB5*01-02. Olanzapine may induce serious leukopenia and neutropenia. HLA typing in this single patient demonstrated a distinct haplotype compared to that previously observed in clozapine-induced haematoxicity. PMID- 11195263 TI - Psychiatric aspects of women's health. AB - A number of psychiatric disorders are present exclusively or more commonly in women. Furthermore, within a particular disorder there may be significant gender differences across demographic and clinical variables, and neurobiological fluctuations across women's menstrual and life cycles may affect the psychobiology of disorders and the pharmacokinetics of pharmacotherapies. Indeed, exploration of gender may serve as a useful heuristic for advancing the field as a whole and for integrating epidemiological and psychobiological data. In this supplement, we highlight three issues that fall under the rubric of 'women's mental health'; premenstrual dysphoric disorder, pharmacotherapy during pregnancy and lactation, and violent trauma and post-traumatic stress disorder in women. Although further work across the range of basic, clinical, and sociopolitical fronts is needed, advances in the pharmacotherapy of premenstrual dysphoric disorder, recent safety data on certain agents in pregnancy, and progress in the management of post-traumatic stress disorder provides cause for clinical PMID- 11195262 TI - Contribution of sodium valproate to the syndrome of inappropriate secretion of antidiuretic hormone. AB - We report the case of a 62-year-old man who was administered sodium valproate (VPA) and who subsequently developed the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). He had been taking VPA for treatment of idiopathic generalized tonic-clonic convulsions since he was 56 years old. After substituting VPA with zonisamide, the serum sodium level returned to normal. We consider this episode of SIADH to be the result of a combination of factors including a weakness of the central nervous system and the long-term administration of VPA. PMID- 11195264 TI - Antidepressant drugs during pregnancy and lactation. AB - As depression is common in women during their childbearing years, many women will experience depression during pregnancy or postpartum. This paper reviews the latest scientific knowledge on the effects of antidepressant drugs during pregnancy and lactation. Information is presented on physical and behavioural teratogenic risks, impaired intrauterine growth, and neonatal toxicity, withdrawal, and death. Risk : benefit considerations, such as the effects of antidepressant drugs on the mother and foetus compared with the effects of untreated severe depression, are discussed to facilitate clinical decision making. Recent studies of the safety of antidepressant drugs during pregnancy and lactation are predominantly reassuring, and should guide and improve the care of depressed childbearing women and their infants. PMID- 11195265 TI - Trauma and post-traumatic stress disorder in women: a review. AB - In the aftermath of traumas such as combat or sexual assault, both men and women may experience similar symptoms, including post-traumatic stress disorder (PTSD). However, epidemiological studies have yielded higher rates of PTSD in women than in men in general populations, and there are also a number of gender differences in clinical presentation after trauma. Thus, in a study by the authors of patients presenting with physical trauma after interpersonal violence, women were more likely than men to have been previously assaulted, or to have sustained injury by a relative or someone known to them, but less likely to have used substances at the time of the assault or to require emergency surgery. A better understanding of the particular factors that contribute to higher rates of PTSD in women may ultimately shed light on the pathogenesis of this complex disorder. This article reviews gender differences in exposure to trauma and subsequent PTSD, emphasizing those features that characterize trauma and PTSD in women. PMID- 11195266 TI - Depression in Kenyan professional women. AB - This was a pilot study to document scores on a general measure of mental health, and to establish the relationship between perceived stress and social support, in Kenyan professional women. Subjects were identified through registered professional bodies, and were asked to self-administer several measures: the General Health Questionnaire, the Perceived Stress Scale, the Network Orientation Scale, and the Social Support Appraisal. Eighty-six out of 120 (71%) subjects responded, of which 22% reported depressive symptoms and 30% indicated that they were coping less well than usual. Increased perceived stress was significantly associated with lower network orientation and lower perceived social support. Further investigation is required in order to draw definitive conclusions. However, these data are of potential utility to Kenyan (and possibly other) professional organizations that intend to put in place systems for the promotion of women's mental health. PMID- 11195267 TI - Violence against women: an emerging health problem. AB - As well as being a violation of human rights, violence against women can be regarded as an 'emerging health problem' of the late twentieth century not because it is new, but because its prevalence and role in the aetiology of ill health has only recently been widely recognized. In this paper we discuss the epidemiology and health impact of violence against women, drawing particularly on data from research in South Africa. Here the prevalence of abuse is between 20% and 30%, which is in keeping with estimates for other countries and research has shown that 1% of women are raped each year. Gender-based violence is an appreciable cause of mortality from homicide and suicide. It is also associated with a range of other health problems, particularly injuries, HIV and sexually transmitted diseases, pregnancy complications and mental health problems. Available estimates suggest that it is associated with considerable costs to the health sector. Roles for the health sector in breaking cycles of abuse are increasingly being recognized and there is a need for appropriate interventions, based on screening, homicide and suicide risk assessment, documentation, information giving and referral to be implemented more widely in health facilities. PMID- 11195268 TI - Quality of life in cancer of the cervix patients. AB - Cancer of the cervix is one of the leading causes of death among female cancer patients in developing countries such as South Africa. Despite this, psychiatric morbidity, including impairment of quality of life, has not been well studied in such patients in this context. A total of 328 Zulu-speaking patients with cervical cancer were interviewed with a structured diagnostic instrument and with a quality of life measure (Quality of Life Index). Quality of life scores were numerically lower than published norms, and lower scores were associated with inpatient status, more advanced stage of the disease, lower Karnofsky physical performance scores, comorbid psychiatric disorder, and lower 'fighting spirit' and more 'helplessness/hopelessness'. The Quality of Life Index is a valuable instrument that can be used by clinicians in order to assess the negative impact of the PMID- 11195269 TI - Diagnosis and treatment of premenstrual dysphoric disorder: an update. AB - Premenstrual dysphoric disorder (PMDD) appears in the appendix of the DSM-IV under the heading 'depressive disorder not otherwise specified'. Yet, recently, a group of experts reached a consensus that PMDD is a distinct clinical entity with characteristic symptoms of irritability, anger, internal tension, dysphoria, and mood lability. PMDD is the more severe form of premenstrual symptomatology, whereas premenstrual syndrome (PMS) is milder and more prevalent and both must be differentiated from premenstrual magnification/exacerbation of an underlying major psychiatric disorder or a medical condition. Accurate assessment and diagnosis of significant premenstrual symptomatology is paramount and can be influenced by subjective perception, retrospective versus prospective reporting, and cultural context. The serotonergic system, which is in a close reciprocal relationship with the gonadal hormones, has been identified as the most plausible target for intervention. Results from randomized placebo-controlled trials in women with PMDD have clearly demonstrated that serotonin reuptake inhibitors (SSRIs), with daily or intermittent dosing, have excellent efficacy and minimal adverse effects and should be considered first-line treatment. Luteal phase only SSRI administration may offer an attractive treatment option for a disorder that is itself intermittent. Hormonal interventions, in particular the suppression of ovulation will eliminate premenstrual symptomatology; however, the benefits-risk ratio of these approaches should be carefully evaluated with the patient. PMID- 11195270 TI - Violent trauma among child and adolescent girls: current knowledge and implications for clinicians. AB - While the incidence and psychiatric correlates of violent trauma among children and adolescents have been well documented, there is less data on the specific ways in which girls are affected by violence. The present review examines current knowledge of the prevalence and effects of violent trauma on female children and adolescents. Domestic and community violence, sexual abuse and war trauma are included. Data on etiology and treatment are also reviewed. Current data indicate that violent trauma, particularly sexual victimization, is highly prevalent among child and adolescent girls. Furthermore, girls appear to be more vulnerable to post-traumatic stress reactions than boys. Some studies report that rates of posttraumatic stress disorder are six times higher in girls, possibly due to the sexual nature of girls' victimization. However, the nature of the exposure distress relationship and the role of protective factors both bear further research. The implications of current findings for clinical practice are discussed, in order to facilitate optimal assessment and treatment of young female victims of violence. PMID- 11195271 TI - Hand washing, cleaning, disinfection and sterilization in health care. PMID- 11195272 TI - Proceedings of the Consensus Conference on Infected Health Care Worker Risk for transmission of bloodborne pathogens. AB - The Laboratory Centre for Disease Control (LCDC) of Health Canada held a consensus conference on "Infected Health Care Workers: Risk for Transmission of Bloodborne Pathogens", on November 20-21, 1996. A wide range of opinion was sought (see Appendix 1 for a list of participants). This document represents the consensus achieved at that meeting as agreed upon by the participants at the final "consensus achieving" session. PMID- 11195273 TI - Preventing infections associated with indwelling intravascular access devices. PMID- 11195274 TI - Preventing the spread of vancomycin-resistant enterococci (VRE) in Canada. PMID- 11195275 TI - Foot care by health care providers. AB - These recommendations have been provided to assist health care providers in performing foot care with the intention of decreasing the transmission of pathogens and resulting infections. It is important that providers of foot care implement these recommendations into their daily practice so that infections associated with foot care can be prevented. PMID- 11195276 TI - Controlling antimicrobial resistance. An integrated action plan for Canadians. PMID- 11195277 TI - Deficiency of gustatory sensitivity to some deterrent compounds in "polyphagous" mutant strains of the silkworm, Bombyx mori. AB - Sawa-J, CSJ02 and N601 x C601 are selected mutant strains of Bombyx mori, which grow on various artificial diets or temporarily ingest various plant leaves. To examine the mechanisms mediating diet breadth of caterpillars, gustatory spike responses of the silkworms, called 'polyphagous" strains, were compared with normal strains, N137 x C146 and C02. There were notable differences in their feeding habits and in their sensitivity to salicin in deterrent cells in the maxillary medial styloconic sensilla and the epipharyngeal sensilla. By contrast, the deterrent cells of all strains responded similarly to strychnine nitrate in a dose-dependent manner. In additional comparisons of Sawa-J and N137 x C146, Sawa J maxillary deterrent cells were significantly less sensitive to phloridzin, amygdalin and arbutin, but responded to some alkaloids and 20-hydroxyecdysone with similar or even higher firing rate. These results suggest that the deficiency of the sensitivity to some deterrent compounds on the deterrent cell of the polyphagous strains may be caused by mutant genes and affects the diet breadth of caterpillars. PMID- 11195278 TI - Actions of neomycin on electrical light responses, Ca2+ release, and intracellular Ca2+ changes in photoreceptors of the honeybee drone. AB - Neomycin, known to inhibit phospholipase C-mediated IP3 formation, was applied in the bath or injected into cells and its effects on electrical light responses were analyzed. Neomycin effects on inositol 1,4,5-trisphosphate- and Ca2+-induced Ca2+ release from the endoplasmic reticulum and/or the light-induced Ca2+ elevation were also studied. Neomycin (0.5 mmol x l(-1)) blocked inositol 1,4,5 trisphosphate-, caffeine-, and Ca2+-induced Ca2+ release. Bath application of neomycin decreased the sensitivity to 20-ms light flashes by a factor of up to 100 and slowed the kinetics of dim flash responses. Intracellularly injected neomycin desensitized the photoreceptors more than 1 log unit, increased the latency, and slowed the rate of rise of the light response. Neomycin (0.5 mmol x l(-1)) in the bath delayed and reduced the transient component of responses to 1 s steps of light at intermediate intensities. It also decreased and slowed the light-induced, and it blocked the caffeine-induced intracellular Ca2+ elevation. The combined pharmacological effects of neomycin are suggested to decrease the Ca2+-mediated amplification of the phototransduction cascade and the Ca2+ mediated acceleration of processes determining the kinetics of light responses. PMID- 11195279 TI - Combined kinematic and electromyographic analyses of proleg function during crawling by the caterpillar Manduca sexta. AB - The planta retractor muscles in the prolegs of Manduca sexta caterpillars are a frequently-used model system for investigating a number of problems in neurobiology. We have combined kinematic and electromyogram analysis of proleg movements during crawling to examine the roles of these muscles during normal behavior. We found that retractor muscle activity is highly stereotyped, and that the primary function of these muscles is to disengage the crochets at the tip of the proleg for the swing phase of crawling. The duration of activity of the muscles was tightly coupled to the phasing of crawling behavior. The stepping patterns of animals changed to accommodate variations in the substrate, but the relative timing of retractor muscle activity was unaffected. There were no clear correlations between the various properties of motoneuronal input to the muscle (duration of activity, number of spikes, peak frequency of spikes) and the resulting muscle length change. Perhaps because it functions partially as a hydrostat, this may represent a neuromuscular system in which a significant part of the control algorithm is embedded in its morphology. PMID- 11195280 TI - Context dependency of a limb withdrawal reflex in the caterpillar Manduca sexta. AB - The proleg withdrawal reflex in the caterpillar Manduca sexta is a robust, well characterized system for investigating the integration of sensory information with centrally patterned behavior. The reflex is evoked by stimulating mechanosensory hairs--planta hairs--located at the tip of each proleg. We studied the expression of this reflex by combining video recordings and electromyographic recordings from the main retractor muscles of the proleg, the principal and accessory planta retractor muscles. In intact animals, the nature of the response depended on the motor context of the animal. Animals which were standing quietly showed great variability in both the kinematic properties of proleg withdrawal, and the corresponding muscle electrical activity. Animals which were hanging upside down from a wooden dowel exhibited a much faster reflex, with retraction of the proleg occurring slightly faster than in standing animals, but re extension of the proleg to the substrate being considerably faster. In crawling animals, expression of the reflex depended on the phase of the crawling cycle during which stimulation occurred. The reflex in a given proleg was suppressed during stance phase of that proleg. During swing phase, however, planta hair stimulation evoked proleg withdrawal, resulting in an assistance reflex. In contrast. isolated abdomens showed much less variability in the reflex. A comparison of the relationship between retractor muscle activity and the resulting proleg movement showed significant correlations between both the duration of activity and the number of muscle spikes, and the size of the associated proleg withdrawal. This is a promising system in which to investigate how central neuronal circuits accomplish context-dependency of motor behavior. PMID- 11195281 TI - Calcium responses to pheromones and plant odours in the antennal lobe of the male and female moth Heliothis virescens. AB - In male moths, the primary olfactory integration centre, the antennal lobe, consists of two systems. The macroglomerular complex processes pheromone information, while the ordinary glomeruli process plant odour information. Females lack a macroglomerular complex. We measured the spatial representation of odours using in-vivo optical recording. We found that: (1) pheromone substances elicited activity exclusively in the MGC. No response was found in female antennal lobes. (2) Plant odours elicited combinatorial activity patterns in the ordinary glomeruli in both males and females. No response was found in the MGC of male moths. (3) A clean air puff often led to activity, in both males and females, suggesting that mechano-sensory information is also processed in the antennal lobe. (4) With an interstimulus interval of 5 or 10 s, strongly activated glomeruli were able to follow the temporal structure of the stimulus, while others lost their phase-locking. Some glomeruli showed "off" responses. These properties were odour dependent. This confirms and extends previous studies, showing the functional significance of the two subsystems for processing olfactory information. Pheromones are coded in a combinatorial manner within the macroglomerular complex, with each glomerulus corresponding to one information channel. Plant odours are coded in an across-glomeruli code in the ordinary glomeruli. PMID- 11195282 TI - Effects of signal duration on the recognition of masked communication signals by the grasshopper Chorthippus biguttulus. AB - The detection and recognition of acoustic communication signals masked by noise was investigated in a grasshopper (Chorthippus biguttulus) whose auditory system exhibits only poor spectral resolution and therefore has to operate in the time domain. The signals of this species consist of numerous identical subunits that enable the receiver, in principle, to make repetitive measurements. We aimed at determining the maximum integration time in this species by using stimuli of different durations under increasing noise levels. As a criterion for recognition the typical phonotactic turning response of the males was evaluated, which is reliably triggered by a female song, and thus is a sensitive indicator for recognition of conspecific signals. When confronted with a long signal (1000 ms) males tolerated a 2.4 dB higher noise level as compared to a short signal (250 ms). Noise tolerance improved with increasing signal duration from 250 ms to 450 ms. Beyond this signal duration, however, no further improvement was observed, indicating an upper limit for temporal integration that corresponds to only five song subunits. The gain in noise tolerance had a slope of 2.7 dB per doubling duration, which corresponds to the expectation derived from an energy detector model (3 dB per doubling duration) rather than to the value expected from signal detection theory (1.5 dB per doubling duration). PMID- 11195283 TI - Wavelength-dependent polarization orientation in Daphnia. AB - The ability to detect and use the polarization of light for orientation is widespread among invertebrates. Among terrestrial insects, the retinula cells that are responsible for polarization detection contain a single visual pigment, either ultraviolet or short (blue) wavelength sensitive. With the exception of a few aquatic insects, the visual pigments underlying polarization sensitivity in aquatic invertebrates have yet to be determined. Here we report that polarotaxis in Daphnia pulex, a freshwater crustacean, is wavelength dependent and most likely mediated by two visual pigments with absorbance maxima in the middle (green) and long wavelength (red) parts of the spectrum. This contrasts with the response of a closely related species, D. magna, in which polarotaxis is wavelength independent and based on a single middle wavelength visual pigment. The visual systems in Daphnia are the first among crustaceans shown to utilize a middle wavelength pigment for polarization detection and, in the case of D. pulex, the first shown to use more than one visual pigment for such a purpose. PMID- 11195284 TI - The critical period for caste determination in Bombus terrestris and its juvenile hormone correlates. AB - The critical period for caste determination and its juvenile hormone (JH III) correlates were studied in Bombus terrestris. Larvae of known age and instar were taken from young colonies, in which they would have been reared as workers, and placed into groups of queenless workers. Under these conditions the critical age for caste determination was 5 days, during the second instar. Endocrine correlates of caste determination were obtained by determining profiles of juvenile hormone titer and juvenile hormone biosynthesis, measured by chiral specific radioimmunoassay and the in vitro radiochemical assay, respectively. By the middle of the second instar prospective queen larvae had significantly higher rates of juvenile hormone biosynthesis and juvenile hormone titer than prospective worker larvae. Based on the coincidence of timing of both the critical period and the appearance of caste-specific juvenile hormone titer, we suggest that juvenile hormone plays a role in the mechanisms that control caste determination in B. terrestris. PMID- 11195285 TI - Stereocilium injury mediates hair bundle stiffness loss and recovery following intense water-jet stimulation. AB - Inner ear hair cells exhibit many pathologies following exposure to intense sound, and the hair bundle is a major site of damage. This paper measures in vitro hair bundle motion on chick cochlear hair cells after intense in vitro and in vivo stimulation to explore the nature of hair bundle injury. Hair bundle stiffness, as well as relative and asymmetric motion of individual stereocilia, is controlled largely by the extracellular tip links, and a change in hair bundle motion was used to assess tip-link destruction following overstimulation. Intense in vitro stimulation caused a loss in stiffness that fully recovered within 10 min post-exposure. Relative and asymmetric stereocilia motion, however, were unchanged following the exposure, implying that tip links remained intact while the core or rootlet of the stereocilia were damaged and subsequently repaired. Intense and prolonged in vivo sound exposures produced stereocilia movements, measured in vitro, that were indicative of damage to stereocilia and tip links. Finally, the relative susceptibility of hair bundles to overstimulation was addressed by comparing stiffness loss with morphological features in the hair bundles. The loss of stiffness significantly increased as the amount of curvature in the hair bundle contour increased. PMID- 11195286 TI - Recent advances in the adjuvant therapy of breast cancer. PMID- 11195287 TI - [Sentinel lymphnode: surgical standard in breast cancer]. AB - Evaluation of the sentinel lymph node (SLN) is capable of avoiding dissection in a high percentage of node negative patients (> 90). It is essential that "useless" treatment not be performed as the negative collateral effects are not justifiable and furthermore present financial laws do not reimburse dissections carried out in the absence of node disease. The intraoperative evaluation of the SL is an extremely expensive procedure, due both to the personnel required and to the time necessary for the patient to remain in the operating room awaiting histology results. In fact, it is far easier to retrieve the SLN in day hospital and to examine the specimen on fixed material and not frozen. Twenty three cases of deferred SLN were evaluated, the results of which were highly reliable because of these, only 3 dissections were performed after an average of 4 days from biopsy. As SL evaluation does not increase the "curability" of the disease but only reduces any eventual complications, we believe it should be restricted to extremely selected and specialistic institutions due to the great economical and organizational cost involved. PMID- 11195288 TI - Adjuvant therapy for patients with node negative breast cancer. PMID- 11195289 TI - [Metastatic breast cancer: what are the objectives?]. AB - The medical approach to the treatment of metastatic breast cancer has changed in the last decade since the introduction of new drugs that demonstrate high activity and better tolerability profiles. The hormonal treatment, usually considered the first choice therapy for ER-positive metastatic breast cancer patients, has seen several improvements with the discovery of new selective aromatase-inhibitor agents and pure antiestrogens. New aromatase-inhibitors have shown higher activity and fewer side effects compared to megestrol acetate in second line treatment. The first line treatment has unchanged so far, but in the next future is possible that different agents, with lower toxicity, will replace tamoxifen since studies comparing this agent with pure antiestrogens or selective aromatase-inhibitors are ongoing. These new drugs would provide a better palliation of metastatic breast cancer in terms of higher clinical benefit, tolerability and quality of life. Chemotherapy is often used in ER-negative patients or in aggressive hormone refractory disease. Randomized trials have demonstrated that anthracyclin-containing regimens were more effective than combinations without anthracyclines. New cytotoxic drugs with high activity, such as taxanes (paclitaxel and docetaxel), vinorelbine, gemcitabine and capecitabine, have been introduced. Compared with older therapies, improved objective response rates and/or improved duration of response have been reported with these newer agents alone or in combination with other drugs. However, no clear improvement of overall survival has been shown so far. Taxanos alone or in combination are today considered the second line treatment of choice and studies are assessing the value of a taxane-anthracycline containing regimen in first line treatment. Some new agents (vinorelbine) showed, alone or in combination, an interesting cost effectiveness ratio with similar or higher "quality adjusted progression free survival" if compared to taxanes. Promising are also the results of agents that own low toxicity with comparable efficacy such as liposomal anthracycline. Attempts to improve overall survival with increased dose intensity or with high dose chemotherapy are disappointing. CONCLUSIONS: Since the goal of treatment of metastatic breast cancer is disease control rather than disease skill i.e. palliation of patients with complications of progressive cancer, the new agents have brought significant improvements (higher response rates, median time to progression, cost benefit and better tolerability). Future progresses for this disease, hopefully even in overall survival, will depend on the introduction of new therapies such as immunotherapy, inhibition of intracellular signaling, interference with tumor angiogenesis, gene-therapy and the development of vaccines. PMID- 11195290 TI - New perspectives in the treatment of non-small cell lung cancer. Introduction. PMID- 11195291 TI - Postoperative chemotherapy in non-small cell lung cancer. PMID- 11195292 TI - Treatment perspectives in advanced non-small cell lung cancer. PMID- 11195293 TI - Do we have good surrogate endpoints for survival in breast cancer studies? PMID- 11195294 TI - The evolution of surgery in non-small cell lung cancer. PMID- 11195295 TI - New drugs in non-small cell lung cancer. PMID- 11195296 TI - Neoadjuvant chemotherapy in non-small cell lung cancer: a standard approach? PMID- 11195297 TI - [Adjuvant therapy in gastric cancer]. AB - In Western countries gastric cancer represents the third cause of death even if in the last twenty years the epidemiology of disease has changed. Surgery remains the treatment of choice and overall survival is still 7-15%. Survival data after curative resection are higher in Japan than in Western countries due to a substantial different surgical approach and "early" diagnosis. In both countries adjuvant treatment has been developed to increase the survival rate and different schedules and polipharmacological schemes have been tested. In Japanese trials a statistical significance in survival was observed with chemoimmunotherapy using chemotherapy as control arm. In Western countries data are not conclusive: most trial used surgery as control arm and sample size was not sufficient to show a significant difference between the two arms. The meta-analysis performed up to now have shown a trend of advantage in survival with adjuvant chemotherapy and many objections can be raised concerning the methodology of the same. In fact there are different types of meta-analyses according to whether they are based on the literature (MAL) or individual patient data (MAP or IPD meta-analysis). With an IPD meta-analysis a search is not only done in the literature for all relevant published trials, but also in the scientific community unpublished trials. For all trials, whether published or not, individual patient data on the endpoint of interest are obtained from the investigators. No meta-analysis performed up to now has adopted this methodology. Recently, combined therapy (CT/RT) has shown interesting results with an increase in DFS and OS. At the moment trials results are not sufficient to consider adjuvant chemotherapy the standard treatment: other large trials are required and a combined approach such as RT, IP chemotherapy, neoadjuvant plus adjuvant chemotherapy may be a future research possibility. PMID- 11195298 TI - [Combination of 5-Fluorouracil and folinic acid--is it still the standard therapy for advanced colorectal carcinoma?]. AB - After a long period in which the only therapeutic approach for the management of colorectal cancer was the optimization of fluoropyrimidine-based chemotherapy, the last few years have seen the emergence of newly active chemotherapeutic agents endowed with novel mechanisms of action, such as oxaliplatin (OHP), irinotecan (CPT11), raltitrexed and oral 5-fluorouracil (5-FU) pro-drugs which can offer new therapeutic possibilities. The availability of these different classes of cytotoxic agents has introduced the possibility of combination chemotherapy. The most widely studied combinations are 5-FU/folinic acid (FA)/CPT11 and 5-FU/FA/OHP, both of which have been tested in two randomized studies. These trials consistently demonstrated that the addition of CPT11 or OHP to widely accepted infusional/bolus 5-FU/FA regimens is superior to the same 5 FU/FA schedule alone in term of response rate (rate of about > 50%) and time to progression. It's worth nothing that both trials with the combination of 5 FU/FA/CPT11 showed a significant survival benefit. Toxicity profiles were more pronounced with the combination therapies but the quality of life evaluation showed that the combinations had no negative impact on the evolution of the global health status over time. A current ongoing randomized study compares 5 FU/FA/CPT11 with 5-FU/FA/OHP in order to identify the best first-line chemotherapy. Preliminary results in terms of objective response and toxicity are similar for both treatments. Raltitrexed is a thymidilate synthase inhibitor with activity comparable to 5-FU and a convenient administration schedule. In our institution, we performed a phase II single center trial to assess the efficacy of the combination of raltitrexed and CPT11. The principal aim of the study was the overall response rate. We observed a very promising 51% overall response rate. Most relevant side effects were diarrhea in about 20% of patients, asthenia and vomiting. Two recent studies have assessed the efficacy and tolerability of raltitrexed-OHP combination therapy. The results showed that the combination is active (ORR: 46-62%) and tolerable. Promising results have also been obtained in phase I studies with the OHP/CPT11 combination. All these data need to be confirmed in phase II-III clinical trials. In conclusion, combination therapy with CPT11 plus 5-FU/FA produces a 2-3 month survival advantage over 5-FU/FA alone and represents the new reference in the first-line chemotherapy of colorectal cancer. The association of 5-FU/FA and OHP improves response rates and progression-free survival. The increase in toxicity of these combinations is predictable and reversible and does not compromise quality of life. These important data suggest that there is now a limited role for single-agent first line chemotherapy of metastatic colorectal cancer. PMID- 11195299 TI - The new European gold standard treatment for rectum cancer. PMID- 11195300 TI - New perspectives in the treatment of gastrointestinal tumors. Introduction. PMID- 11195301 TI - Cancer vaccines. PMID- 11195302 TI - Allogeneic stem cell transplantation and non-myeloablative conditioning regimens. PMID- 11195303 TI - [Effectiveness of precautionary chemotherapy in gastric cancer]. AB - Gastric cancer is a very aggressive disease. Surgery is the treatment of choice, with less than 30% 5-year survival for patients with complete resection. Although the incidence of gastric cancer in Western countries has declined progressively in recent decades, the prognosis of the disease has not changed in the last 30 years, with 5-year global survival rates between 7 and 15%. The achievement of an increase in the rate of cure would be therefore an important goal, but the efficacy of adjuvant chemotherapy in this disease is still controversial. The aim of this overview is to document that postoperative chemotherapy may be effective in patients operated with curative intent for gastric cancer. We reviewed the results of randomized trials comparing adjuvant chemotherapy versus surgery alone, divided into those performed in the West and those performed in Asia, and according to publication period. We also reported the preliminary results of an intergroup randomized study of postoperative chemoradiation versus follow-up. Then, we summarized and discussed the results of the 3 meta-analyses, published respectively in 1993, 1999, and 2000, that evaluated the combined results from the over mentioned trials. Singular studies reported conflicting results and failed to show a clear indication for chemotherapy, but they were open to criticisms, due to methodological and therapeutical limitations. The meta analysis published by Hermans showed a non-significant trend in favor of adjuvant treatment. This analysis was later criticized, and, in response, the author published an update in 1994 in which he recalculated a significant odds ratio. Meta-analyses by Earle and Mari indicated that postoperative chemotherapy produces a small survival benefit in patients with curatively resected gastric carcinoma. Subgroup analyses produced some interesting findings. There was a partial evidence of better results with chemotherapy regimens containing anthracyclines, but it is possible that the results of the ongoing trials testing regimens including cisplatin will add more reliable information about the new regimens. Studies with longer follow-up maintained a trend towards benefit from adjuvant therapy, indicating that long-term survival may be afforded by treatment, as opposed to simply delaying relapse. Finally, there was a trend towards a larger magnitude of the effect when analyses were restricted to trials which included higher risk patients. In conclusion, the results of the 3 meta analyses suggest that adjuvant chemotherapy may be effective. However, other studies to confirm an effective treatment and to find new therapeutic combination or strategies in the field of adjuvant therapy for gastric carcinoma are warranted. PMID- 11195304 TI - The role of attention shifts in the categorization of continuous dimensioned stimuli. AB - Results of human category learning experiments, using stimulus dimensions with binary values, have implicated a rapidly acting mechanism of attention shifts. Theories of categorization desire that stimuli with binary, discrete and continuous valued dimensions should all be treated similarly. Theoretical analyses of attention shifting, however, have up to now only been developed for shifts between features, or shifts between entire dimensions, not shifts within dimensions. Here we present a model of how people learn to discriminate categories made up of stimuli with continuous-valued dimensions. The model uses rapid shifts in attention within stimulus dimensions to reduce errors during learning; the model generalizes J. K. Kruschke's (Psychological Review, 99, 22 44, 1992) ADIT model. In an experiment in category learning, subjects were trained to discriminate four bivariate normal distributions that are presented with differential base rates. The base-rate manipulation produces several qualitative effects, for which the model accounts very well. With attention shifting turned off, the model fails to account for some aspects of the data, suggesting that attentions shifts are an important mechanism in the model. PMID- 11195305 TI - A shift of attention may be necessary, but it is not sufficient, for the generation of the Simon effect. AB - The Simon effect is the performance advantage for spatially corresponding, compared to non-corresponding, target-response ensembles when the location of the target is task irrelevant. In four experiments, we tested the predictions of the attention-shift account of the Simon effect. In all experiments, subject made choice responses with respect to the identity of a central target that followed a spatially non-informative peripheral precue. The first experiment showed a Simon effect away from the precue when the precue was a go/no-go signal: responses to spatially non-corresponding precue-response pairs were faster than responses to spatially corresponding precue-response pairs. The results of the second experiment suggested that this "reverse" Simon effect was not due to inhibition. In the third experiment, a secondary working memory task required the encoding, and later recall, of "oddball" precues. Although the Simon effect was absent, larger Simon effects towards the precue (i.e., responses were faster to spatially corresponding, compared to non-corresponding, precue-response ensembles) were correlated with poorer performance on the memory task. In the last experiment, the identity of completely non-informative precues was congruent, incongruent, or unrelated to the identity of the target. With precues that were unrelated to the identity of the target, there was a Simon effect towards the precues. Conversely, the Simon effect occurred away from the precue when the identity of the precue was related to that of the target. The findings suggest that a shift of attention alone is not sufficient to produce the Simon effect. Rather, the shift of attention must originate from an intentionally defined object. The results are discussed within a framework that integrates the attention-shift and referential coding hypotheses. PMID- 11195306 TI - Phase congruency: a low-level image invariant. AB - Phase congruency is a low-level invariant property of image features. Interest in low-level image invariants has been limited. This is surprising, considering the fundamental importance of being able to obtain reliable results from low-level image operations in order to successfully perform any higher level operations. However, an impediment to the use of phase congruency to detect features has been its sensitivity to noise. This paper extends the theory behind the calculation of phase congruency in a number of ways. An effective method of noise compensation is presented that only assumes that the noise power spectrum is approximately constant. Problems with the localization of features are addressed by introducing a new, more sensitive measure of phase congruency. The existing theory that has been developed for 1D signals is extended to allow the calculation of phase congruency in 2D images. Finally, it is argued that high-pass filtering should be used to obtain image information at different scales. With this approach, the choice of scale only affects the relative significance of features without degrading their localization. PMID- 11195308 TI - Subitizing and its subprocesses. AB - When people are presented with small sets of elements such as dots they can very easily determine their number. This ability has been called subitizing. The present paper reports results from four experiments. The discussion focuses on the question whether one or two psychological processes have to be assumed for this task of subitizing. Taken together our results support the two-process theories. In particular, a distinction between a process of separation and a process of enumeration is suggested. Experiments 3 and 4 support the canonical pattern hypothesis. Canonical patterns are processed substantially faster than noncanonical patterns. Furthermore, if a complex pattern can be broken down into small canonical patterns, then participants follow a partition and add strategy. PMID- 11195307 TI - The missing fundamental phenomenon in temporal vision. AB - Subjective flicker rates were measured for compound waveforms consisting of five harmonics without a fundamental component. It was found that observers perceived a rate at the fundamental frequency, although energy at this frequency was not included in the signals. In auditory pitch sensation this is called the missing fundamental phenomenon, and an analogous finding is known to occur in spatial vision. Moreover, observers perceived the flicker rates at the fundamental frequency even in the random-phase conditions, in which the period of the fundamental component is unclear in the real waveforms. The results indicate that the perceived flicker rates are not detected from the temporal waveforms per se. One possible mechanism for extracting such a periodicity in the signal is an auto correlation function to the real temporal waveforms. PMID- 11195309 TI - Perceptual inertia: spatial attention and warning foreperiod? AB - Perceptual inertia refers to a potential explanation for the observation that during a short period after stimulus onset, the visual system is insensitive to discriminatory detail. The present study attempted to replicate this empirical result in a simple one-item letter-identification task. The results provided little if any support for the construct of perceptual inertia. In the five experiments reported, evidence consistent with perceptual inertia was only obtained in Experiment 5. However, the Experiment 5 results can at least equally parsimoniously be explained in terms of two standard explanatory factors: an effect of precuing of the target position (selective attention) and foreperiod duration (general preparation). PMID- 11195310 TI - Selective cyclooxygenase-2 inhibitors: hope and facts. PMID- 11195311 TI - Usefulness of criteria for spondyloarthropathies. PMID- 11195312 TI - Contribution of arthroscopy and magnetic resonance imaging to the evaluation of painful knee osteoarthritis. AB - In knee osteoarthritis, arthroscopy provides valuable information that suggests an original approach to the disease. In combination with recent imaging study data, this information can be used to develop a novel concept of the evaluation of knee osteoarthritis. The main mechanisms responsible for flares of the disease seem to be synovitis, degenerative meniscal disease, and subchondral bone lesions. Treatments targeted at each of these mechanisms can be used as appropriate. Determination of the exact nature of the lesions can be difficult and relies at present on sophisticated investigations not readily available in everyday practice. Further work is needed to determine how a finer analysis of symptoms and signs in combination with simple investigations can differentiate between the various pathological patterns of knee osteoarthritis. PMID- 11195313 TI - Hypercalciuria. AB - Hypercalciuria is a biological syndrome defined as excretion in the urine of more than 0.1 mmol/kg/24 hours of calcium in the absence of dietary manipulation. A number of endocrine, renal, and bone diseases can cause hypercalciuria. Urinary calcium excretion is substantially influenced by dietary intakes of calcium, sodium, protein, carbohydrates, alcohol, and potassium: a poorly balanced diet can result in hypercalciuria. Recently, there has been a burst of interest in the molecular underpinnings of rare nephrolithiasis syndromes, which have been shown to result from mutations in the CLCN5 chloride channel gene. Mutations affecting the calcium-sensing receptor (CaSR) have been identified in other forms of hypercalciuria. Idiopathic hypercalciuria is defined as hypercalciuria that persists after correction of dietary imbalances and has no detectable cause. The classification suggested by Pak ("absorptive" hypercalciuria [with three types] and "renal" hypercalciuria) is controversial and of little assistance in clinical practice. Three mechanisms can be incriminated in idiopathic hypercalciuria: increased intestinal absorption of calcium, defective reabsorption of calcium by the renal tubule, and increased bone resorption. Overexpression of the vitamin D receptor (VDR) and deficiencies in renal tubule enzymes may also be involved. Bone mineral density is moderately decreased in idiopathic hypercalciuria, particularly in the renal type. The risk of vertebral fracture seems increased, however. Overproduction of calcitriol and cytokines that stimulate bone resorption have been incriminated in the bone loss. Treatment of the cause is essential in secondary hypercalciuria (dietary advice, treatment of an underlying disease, etc.). A diet low in sodium and meat and containing no more than 800 mg of calcium per day is advocated in idiopathic hypercalciuria. Hydrochlorothiazide therapy is warranted in patients with osteopenia and an inadequate response to dietary therapy. PMID- 11195314 TI - Can some cases of 'possible' spondyloarthropathy be classified as 'definite' or 'undifferentiated' spondyloarthropathy? Value of criteria for spondyloarthropathies. Spanish Spondyloarthropathy Study Group. AB - OBJECTIVES: When evaluating patients for spondyloarthropathy, clinicians use the 'possible spondyloarthropathy' category to indicate that they are unsure about the diagnosis. We sought to determine whether Amor's criteria or the European Spondyloarthropathy Study Group (ESSG) criteria could lift thi uncertainty. PATIENTS AND METHODS: During a Spanish study designed to validate criteria for spondyloar thropathies, 102 patients were classified in the 'possible spondyloarthropathy' category. We divided these patients into subgroups based on whether or not they met criteria for spondyloarthropathy. We compare baseline characteristics (N = 102) and five-year outcomes (N = 52) in these subgroups. RESULTS: The following features were significantly more common in the subgroups of patients who met Amor's criteria for spondyloarthropathy: oligoarthritis, heel pain, uveitis, balanitis, family history of spondyloarthropathy, an presence of the HLA B27 antigen. No differences were found for age at symptom onset, disease duration, buttock pain, gender, dactylitis, diarrhea, or psoriasis. Of the 52 patients followed up for five years, 17 me Amor's criteria at baseline and 13 were subsequently found to have definite spondyloarthropathy, whic was undifferentiated in six cases. There were only three cases of spondyloarthropathy among the 2 patients who did not meet Amor's criteria at baseline. Of the 28 patients who met ESSG criteria at baseline, 13 had spondyloarthropathy versus three of the 17 patients who did not meet ESSG criteria at baseline CONCLUSION: Amor's criteria or the ESSG criteria allow early classification of most patients with 'possible spondyloarthropathy' and early identification of undifferentiated spondyloarthropathy corresponding to minimal-symptom or incipient disease. In this study, Amor's criteria performed better than the ESSG criteria. PMID- 11195315 TI - Altered bone mineral metabolism in patients with osteoarthritis. AB - OBJECTIVE: Investigation of the relationship between osteoarthritis (OA) and mineral density, and determination of any alteration in bone mineral, metabolism as assessed by biochemical markers of bone resorption and formation. METHODS: Forty females and 20 males were included in the study. Spinal OA as well as knee OA were defined from radiographs and graded according to Lane et al.'s and Spector et al.'s scoring systems. Bone mineral density (BMD) of the lumbar spine was measured by osteo CT. Bone turnover rates were estimated by measuring biochemical markers of bone resorption (urinary deoxypyridinoline) and bone formation (bone-specific alkaline phosphatase). Forty females and 20 males of the same age were studied as a control group. RESULTS: BMD was greater in women with spinal OA as compared to controls (P < 0.05). Also, males with OA had a non significantly higher BMD than controls. The bone resorption markers were higher than normal values. However, they were lower than the control group. Similarly, the bone formation markers were lower as compared to the control group. CONCLUSION: Spinal OA is associated with higher BMD. This protective effect of spinal OA against osteoporosis may be mediated through decreased rate of bone turnover. PMID- 11195316 TI - Acquired lumbar kyphosis caused in adults by primary paraspinal myopathy. Epidemiology, computed tomography findings, and outcomes in a cohort of 23 patients. AB - Acquired lumbar kyphosis in adults, also called bent spine syndrome (BSS), is probably due to primary tardive myopathy affecting the paraspinal muscles. OBJECTIVES: To define family history and other factors associated with BSS, to score functional disability and pain in BSS using visual analog scales (VASs), to determine the pace of disease progression during follow-up, and to define computed tomography (CT) findings comparatively with age- and sex-matched controls. PATIENTS AND METHODS: Twenty-three patients (20 women and three men; mean age, 72.8 years) with a mean disease duration of 8.1 years at presentation and a mean follow-up of 3.5 years underwent a medical interview, a physical examination, and yearly CT scans with muscle density measurement at several vertebral levels (T4, T10, L1, L3, and L5). RESULTS: Mean age at BSS onset was 64.6 years (range, 56-72). In 12 of the 23 cases, a family history of BSS was highly likely. Thirteen patients had performed heavy manual labor at some time during their lives. At completion of follow-up, the mean functional VAS score was 74.5 mm, the mean Eifel score was 16/24, and the mean pain VAS score was 72.4 mm. Mean muscle density obtained by pooling measurements at all vertebral levels was 12.6 +/- 31 Hounsfield units (HU) in the patients and +36.9 +/- 21 HU in the controls. During the 3.5-year follow-up, the mean loss in muscle density was 6.9 +/- 16 HU in the patients; in contrast, no muscle density difference was found between two groups of low back pain patients without BSS aged 65 years and 72 years, respectively (36.2 +/- 15 HU vs 38.6 +/- 26 HU). CONCLUSION: BSS causes major functional disability and pain, which worsen over time. The decrease in paraspinal muscle density extends along the entire spine and becomes increasingly marked over time. PMID- 11195317 TI - Low back pain in hospital outpatients in Lome (Togo). AB - OBJECTIVE: To determine the patterns of low back pain and the conditions associated with this symptom in outpatients attending the rheumatology unit of the Lome Teaching Hospital. METHODS: Medical records of patients seen over a ten year period were studied retrospectively. RESULTS: Among the 9,065 patients seen during the study period, 3,204 (35.34%; 1,850 women and 1,354 men) had low back pain. Mean age at onset was 41 years, and mean duration of low back pain was three years. Diseases associated with low back pain were as follows: degenerative spinal disease, N = 3,054 (95.32%); spinal infections, N = 79 (2.47%); spondyloarthropathies, N = 44 (1.37%); and tumors, N = 27 (0.84%). The patterns of degenerative spinal disease included low back pain (N = 1,535, 47.91%), low back pain with nerve root pain suggestive of disk herniation (N = 1,108, 34.58%), and low back pain with nerve root pain and claudication suggestive of lumbar spinal stenosis (N = 411, 12.83%). Schober's index was abnormal in 831 of the 1,408 patients (59%) with acute pain or disk herniation. Most patients with lumbar spinal stenosis were women (72.26%) and were aged 35 to 64 years. Findings suggestive of tuberculosis were present in 62 of the 79 patients with lumbar spinal infection. Among the 44 patients with spondyloarthropathies, 15 had ankylosing spondylitis and 11 had infection with the human immunodeficiency virus (HIV). Multiple myeloma was present in ten patients and metastatic tumors in eight. CONCLUSION: Low back pain seems to be as common in sub-Saharan Africa as in occidental countries, with a prevalence of one-third among rheumatology outpatients. Lumbar spinal stenosis seems more common than in the occident and is mainly observed in woman. Schober's index is not useful for measuring forward bending of the lumbar spine in Africans. The epidemiology of spondyloarthropathies in sub-Saharan Africa has been changed by the expanding HIV epidemic, despite the low prevalence of the HLA B27 phenotype. PMID- 11195318 TI - Weismann-Netter-Stuhl syndrome: first Brazilian case reports. AB - Weismann-Netter-Stuhl syndrome was first described in 1954 and is defined by an anterior curvature of the bones of the lower limbs, usually bilateral and symmetrical. Since its initial description, 82 cases were reported, including only 14 pediatric patients. The authors report two cases of this syndrome. One patient was an adult who presented with almost all the characteristic features of the disease. The second case was a 12-year-old girl who also presented with severe bone deformities of the upper limbs. Weismann-Netter-Stuhl syndrome is probably more common than previously reported and must be included in the differential diagnosis of rickets/osteomalacia, congenital syphilis and some cases of Paget's disease. PMID- 11195319 TI - Remitting asymmetrical pitting oedema in systemic lupus erythematosus: two cases studied with magnetic resonance imaging. AB - To our knowledge, only three cases of remitting symmetrical pitting oedema in systemic lupus erythematosus have been reported so far. This is the first report of two patients with asymmetrical pitting oedema and systemic lupus erythematosus. The first patient presented two consecutive episodes of unilateral oedema. The first episode involved the distal part of the right lower extremity and remitted spontaneously while the second involved the volar region of the left wrist and distal half of the forearm and promptly responded to steroids. Magnetic resonance imaging of the left wrist and forearm showed tenosynovitis of the flexor tendons and subcutaneous oedema. The second patient instead developed a single episode of pitting oedema of the distal part of the right lower extremity that resolved spontaneously. Magnetic resonance imaging of the right ankle and foot showed subcutaneous oedema without involvement of the tendon sheaths or osteoarticular and ligamental structures. These two cases suggest that pitting oedema in systemic lupus erythematosus may occasionally be asymmetric and associated or not with tenosynovitis. PMID- 11195321 TI - Uncommon arthritis as presenting manifestation of silent Crohn's disease. PMID- 11195320 TI - A possible association between Chlamydiae psittacci infection and temporal arteritis. AB - Some arguments are in favor of the role of Chlamydia in the pathogenesis of atherosclerosis and some vasculitis. Illustrating this possible relation, we report the case of a patient developing consecutively a Chlamydia psittacci infection and a temporal arteritis. A 73-year-old woman, with no significant medical history, was hospitalized for constitutional symptoms. Three weeks before, she had described fever and sore throat of two days' duration. Since that time, she had remained exhausted and developed a mild intermittent claudication of the jaws. Clinical examination was poor. A biological inflammatory syndrome was noticed. Chest X-ray revealed bilateral interstitial opacities. The titer of anti-C. psittaci antibodies was significant (positive 1g G at 1/2048). Soon after initiation of doxycycline, a temporal arteritis biopsy was performed, due to the persistence of clinical symptoms and high inflammatory syndrome, conclusive for the diagnosis of temporal arteritis. Corticotherapy was added to antibiotic therapy, resulting in the decrease of inflammatory syndrome and an improvement in the general status of the patient. X-ray opacities decreased in three weeks. Serological control after three months showed a decrease of the titer of anti-C. psittacci antibodies to 1/256, confirming the initial diagnosis of Chlamydia pneumopathy. Our observation could provide one more argument for the role of bacteria-like Chlamydia in the pathogenesis of vascular diseases. Prospective seroepidemiological and molecular biology studies could allow us to clarify the association between Chlamydia infections and inflammatory vasculitis-like temporal arteritis. PMID- 11195322 TI - Pathophysiology of osteoarthritis. PMID- 11195323 TI - The chondrocyte: from cell aging to osteoarthritis. PMID- 11195324 TI - Proinflammatory cytokines, prostaglandins, and the chondrocyte: mechanisms of intracellular activation. PMID- 11195325 TI - Interest of animal models in the preclinical screening of anti-osteoarthritic drugs. PMID- 11195326 TI - Gene therapy in osteoarthritis. PMID- 11195327 TI - Autologous chondrocyte implantation for cartilage defects: development and applicability to osteoarthritis. PMID- 11195328 TI - Reasonable osteoporosis prevention: hormone replacement therapy, SERM, or bisphosphonate? PMID- 11195329 TI - Rehabilitation therapy in chronic low back pain. PMID- 11195330 TI - Positron emission tomography: how useful is this new functional imaging tool in rheumatology? PMID- 11195331 TI - A genetic map of cucumber composed of RAPDs, RFLPs, AFLPs, and loci conditioning resistance to papaya ringspot and zucchini yellow mosaic viruses. AB - The watermelon strain of papaya ringspot virus (PRSV-W) and zucchini yellow mosaic virus (ZYMV) are potyviruses that cause significant disease losses in cucumber. Resistances have been identified primarily in exotic germplasm that require transfer to elite cultivated backgrounds. To select more efficiently for virus resistances, we identified molecular markers tightly linked to PRSV-W and ZYMV resistances in cucumber. We generated F6 recombinant inbred lines (RILs) from a cross between Cucumis sativus L. 'Straight 8' and a line from 'Taichung Mou Gua', TMG1 (susceptible and resistant, respectively, to both viruses), and studied the segregations of amplified fragment length polymorphism (AFLP) markers, randomly amplified polymorphic DNAs (RAPDs), restriction fragment length polymorphisms (RFLPs), and resistances to PRSV-W and ZYMV. A 353-point map of cucumber was generated, delineating 12 linkage groups at LOD 3.5. Linkage arrangements among RFLPs were consistent with previously published maps; however linkages among RAPDs in our map did not agree with a previously published map. Resistances to PRSV-W and ZYMV were tightly linked (2.2 cM) and mapped to the end of one linkage group. One AFLP cosegregated with resistance to ZYMV. PMID- 11195332 TI - The sex-determining gene doublesex in the fly Megaselia scalaris: conserved structure and sex-specific splicing. AB - The well-known sex-determining cascade of Drosophila melanogaster serves as a paradigm for the pathway to sexual development in insects. But the primary sex determining signal and the subsequent step, Sex-lethal (Sxl), have been shown not to be functionally conserved in non-Drosophila flies. We isolated doublesex (dsx), which is a downstream step in the cascade, from the phorid fly Megaselia scalaris, which is a distant relative of D. melanogaster. Conserved properties, e.g., sex-specific splicing, structure of the female-specific 3' splice site, a splicing enhancer region with binding motifs for the TRA2/RBP1/TRA complex that activates female-specific splicing in Drosophila, and conserved domains for DNA binding and oligomerization in the putative DSX protein, indicate functional conservation of dsx in M. scalaris. Hence, the dsx step of the sex-determining pathway appears to be conserved among flies and probably in an even wider group of insects, as the analysis of a published cDNA from the silkmoth indicates. PMID- 11195333 TI - Coevolution of A and B genomes in allotetraploid Triticum dicoccoides. AB - Data is presented on the coevolution of A and B genomes in allotetraploid wheat Triticum dicoccoides (2n = 4x = 28, genome AABB) obtained by genomic in situ hybridization (GISH). Probing chromosomes of T. dicoccoides with DNA from the proposed A/B diploid genome ancestors shows evidence of enriching A-genome with repetitive sequences of B-genome type. Thus, ancestral S-genome sequences have spread throughout the AB polyploid genome to a greater extent than have ancestral A-genome sequences. The substitution of part of the A-genome heterochromatin clusters by satellite DNA of the B genome is detected by using the molecular banding technique. The cause may be interlocus concerted evolution and (or) colonization. We propose that the detected high level of intergenomic invasion in old polyploids might reflect general tendencies in speciation and stabilization of the allopolyploid genome. PMID- 11195334 TI - DNA content, rDNA loci, and DAPI bands reflect the phylogenetic distance between Lathyrus species. AB - The nuclear DNA content, the proportion of A+T base pairs, the chromosomal positions of 5S and 25S rRNA genes, as well as of DAPI (4,6-diamidino-2 phenylindole) bands are described for seven species belonging to three different sections of the genus Lathyrus. These data and chromosome measurements allowed to establish precise idiograms and to discriminate most of the chromosome pairs of the seven species. The karyotypic features correlate well with the phylogenetic distances between these species. PMID- 11195335 TI - Molecular contribution to selection of intergeneric hybrids between sugarcane and the wild species Erianthus arundinaceus. AB - Erianthus arundinaceus has great potential as a germplasm source for better ratoonability, vigour, tolerance to environmental stresses, and disease resistance in sugarcane. Many unsuccessful attempts have been made to introduce these characters into modern sugarcane cultivars. We report on significant progress made since molecular tools were implemented. Sequence-tagged PCR, revealing size variation in the 5S rDNA cluster, was performed on intact leaf tissue to identify genuine hybrids six weeks after germination. This early screening of seedlings avoids the loss of genuine hybrids due to competition with selfed progeny. Of 96 crosses made involving female Saccharum officinarum or sugarcane cultivars (Saccharum spp.) and male E. arundinaceus, 26 were fertile producing 1328 seedlings. Thirty-seven genuine hybrids were unequivocally identified but only 19 have survived. Genuine hybrids were produced from only three crosses, all involving S. officinarum as the female parent. Chromosome elimination was observed in all seven hybrids analyzed using genomic in situ hybridization (GISH). Very little cross-hybridization was observed between the genomes of the two species after GISH, confirming recent molecular studies which showed that E. arundinaceus is quite distant from the genus Saccharum. The major limitation in the introgression of E. arundinaceus resides now in the apparent sterility of the hybrids. PMID- 11195336 TI - Visualization of A- and B-genome chromosomes in wheat (Triticum aestivum L.) x jointed goatgrass (Aegilops cylindrica Host) backcross progenies. AB - Wheat (Triticum aestivum) and jointed goatgrass (Aegilops cylindrica) can cross with each other, and their self-fertile backcross progenies frequently have extra chromosomes and chromosome segments, presumably retained from wheat, raising the possibility that a herbicide resistance gene might transfer from wheat to jointed goatgrass. Genomic in situ hybridization (GISH) was used to clarify the origin of these extra chromosomes. By using T. durum DNA (AABB genome) as a probe and jointed goatgrass DNA (CCDD genome) as blocking DNA, one, two, and three A- or B genome chromosomes were identified in three BC2S2 individuals where 2n = 29, 30, and 31 chromosomes, respectively. A translocation between wheat and jointed goatgrass chromosomes was also detected in an individual with 30 chromosomes. In pollen mother cells with meiotic configuration of 14 II + 2 I, the two univalents were identified as being retained from the A or B genome of wheat. By using Ae. markgrafii DNA (CC genome) as a probe and wheat DNA (AABBDD genome) as blocking DNA. 14 C-genome chromosomes were visualized in all BC2S2 individuals. The GISH procedure provides a powerful tool to detect the A or B-genome chromatin in a jointed goatgrass background, making it possible to assess the risk of transfer of herbicide resistance genes located on the A or B genome of wheat to jointed goatgrass. PMID- 11195337 TI - Production and meiotic pairing behaviour of new hybrids of winter wheat (Triticum aestivum) x winter barley (Hordeum vulgare). AB - New winter wheat (Triticum aestivum L.) x winter barley (Hordeum vulgare L.) hybrids produced using cultivated varieties (wheat 'Martonvasari 9 krl'(Mv9 krl) x barley 'Igri', Mv9 krl x 'Osnova', 'Asakazekomugi' x 'Manas') were multiplied in tissue culture because of the high degree of sterility and then pollinated with wheat to obtain backcross progenies. Meiotic analysis of the hybrids Mv9 krl x 'Igri' and 'Asakazekomugi' x 'Manas' and their in vitro regenerated progenies with the Feulgen method revealed 1.59 chromosome arm associations per cell in both initial hybrids. The number of chromosome arm associations increased after in vitro culture to 4.72 and 2.67, respectively, in the two combinations. According to the genomic in situ hybridization (GISH) analysis, wheat-barley chromosome arm associations made up 3.6% of the total in the initial Mv9 krl x 'Igri' hybrid and 6.6% and 16.5% of the total in in vitro regenerated progenies of the 'Asakazekomugi' x 'Manas' and Mv9 krl x 'Igri' hybrids, respectively. The demonstration by GISH of wheat-barley chromosome pairing in the hybrids and especially in their in vitro regenerated progenies proves the possibility of producing recombinants between these two genera, and thus of transferring useful characters from barley into wheat. In vitro conditions caused an increase in chromosome arm association frequency in both combinations and in fertility in some regenerants. PMID- 11195338 TI - A maize chromosome 3 addition line of oat exhibits expression of the maize homeobox gene liguleless3 and alteration of cell fates. AB - Maize chromosome addition lines of oat offer the opportunity to study maize gene expression in oat and the resulting phenotypes. Morphological examination of a maize chromosome 3 addition line of oat showed that this line exhibited several morphological abnormalities including a blade-to-sheath transformation at the midrib region of the leaf, a hook-shaped panicle, and abnormal outgrowth of aerial axillary buds. Dominant mutations in the maize liguleless3 (lg3) homeobox gene result in a blade (distal)-to-sheath (proximal) transformation at the midrib region of the leaf. Ectopic expression of the dominant mutant Lg3 allele is believed to cause the phenotype. Therefore, we suspected that the maize lg3 gene, which is located on maize chromosome 3, was involved in the phenotypes observed in the maize chromosome 3 addition line of oat. Genetic analyses of an oat BC1F2 family segregating for maize chromosome 3 showed that the presence of a stable maize chromosome 3 was required for the expression of these cell fate abnormalities. RNA expression analysis of leaf sheath tissue from oat plants carrying maize chromosome 3 demonstrated that maize LG3 transcripts accumulated in oat, indicating that this expression is associated with the blade-to-sheath transformation, hook-shaped panicle and outgrowth of aerial axillary bud phenotypes. Our results demonstrate that the maize chromosome addition lines of oat are useful genetic stocks to study expression of maize genes in oat. PMID- 11195339 TI - DNA content, karyotypes, and chromosomal location of 18S-5.8S-28S ribosomal loci in some species of bivalve molluscs from the Pacific Canadian coast. AB - The DNA content of 10 species of bivalve molluscs from British Columbia coast was determined by image analysis, and the karyotypes of the horse clam Tressus capax, the bent-nose macoma Macoma nasuta, and the nuttall's mahogany clam Nuttallia nuttallii are described here for the first time. We also have analyzed the location of rDNA loci using a 28S-5.8S-18S probe in four of these species: Mytilus californianus, M. trossulus, Macoma nasuta and N. nuttallii. Results obtained report new data about cytogenetic characteristics of bivalve molluscs. PMID- 11195340 TI - Molecular characterization and chromosomal distribution of species-specific repetitive DNA sequences from Beta corolliflora, a wild relative of sugar beet. AB - Repetitive DNA sequences have been isolated from a Sau3AI plasmid library of tetraploid Beta corolliflora (2n = 4x = 36), a wild relative of sugar beet (B. vulgaris). The library was screened by differential hybridization with genomic DNA of B. corolliflora and B. vulgaris. When used as probes for Southern hybridization of genomic DNA, six clones were determined to represent highly repetitive DNA families present only in the B. corolliflora genome. Five other sequences were highly repetitive in B. corolliflora and low or single copy in B. vulgaris. The insert size varied between 43 bp and 448 bp. Two sequences pBC1279 and pBC1944 displayed strong homology to a previously cloned satellite DNA from B. nana. With one exception, sequences are tandemly arranged as revealed by a typical ladder pattern after genomic Southern hybridization. The chromosomal distribution of five probes was determined by fluorescence in situ hybridization (FISH) of mitotic metaphases from B. corolliflora and a triploid hybrid between B. vulgaris and B. corolliflora. Three sequences were spread along all chromosome arms of B. corolliflora while one sequence was present on only six chromosomes. The chromosome-specific sequence pBC216 was found in close vicinity to the 5S rDNA located on B. corolliflora chromosome IV. This set of species-specific sequences has the potential to be used as probes for the identification of monosomic alien addition lines and for marker-assisted gene transfer from wild beet to cultivated beet. PMID- 11195341 TI - Physical localization of single-copy sequences on pachytene chromosomes in maize (Zea mays L.) by chromosome in situ suppression hybridization. AB - A new approach for locating single-copy DNA sequences on pachytene chromosomes of maize (Zea mays L.) was developed. A cosmid clone with homologous sequences to a molecular marker (umc105a) linked to a quantitative trait locus (QTL) for resistance against sugarcane borer (SCB) was physically mapped by fluorescence in situ hybridization (FISH) to the short arm of chromosome 9. The marker umc105a was genetically placed in the centromeric region. To suppress signals generated by maize repetitive DNA, competitive in situ suppression (CISS) hybridization was necessary to obtain specific signals from umc105a. A centromere specific DNA probe (CentC) was used in a double-labeling technique as a reference marker. Fluorescence signals generated by umc105a cosmid and CentC were specific and highly reproducible. Thus the single-copy DNA sequence of umc105a was physically localized on the short arm of chromosome 9 near the telomere. This is the first report of physical localization of single-copy DNA sequence by CISS hybridization to a maize pachytene chromosome. PMID- 11195342 TI - Different classes of retrotransposons in coniferous spruce species. AB - We have used the conservation of reverse transcriptase and integrase domains among retroelements to PCR-amplify three well-known types of these mobile genetic elements. Reverse transcriptase sequences from Ty1-copia were identified in spruce in this way, as well as integrase sequences from the Ty3-gypsy group. Using these sequences as probes against a Picea glauca genomic bank, individual members from the LTR (long terminal direct repeat) groups were obtained. A partial Ty1-copia-type element named Spcl was isolated along with a Ty3-gypsy type element named Spdl. Genomic Southern hybridizations revealed the complexity and high copy number of LTR retrotransposons in black and white spruce. PMID- 11195343 TI - Lineage sorting accounting for the disassociation between chloroplast and mitochondrial lineages in oaks of southern France. AB - Dumolin-Lapegue et al. (Mol. Biol. Evol. 15: 1321-1331. 1998) suggested that recurrent inversions of a 4-bp sequence of the mtDNA nad4-1/2 locus due to intramolecular recombination were responsible for the disassociation of chloroplast and mitochondrial genomes of French oaks. Based on their PCR-RFLP (PCR-restriction fragment length polymorphism) data obtained from three noncoding spacers, a minimum spanning network representing the phylogeny of the cpDNA was reconstructed. The mapping of alleles b and c of the mtDNA nad4-1/2 locus on the cpDNA network revealed a nonrandom distribution, which contradicted the expected patterns when repeated, and ongoing inversions had been occurring. The fact that polymorphisms (a mixed c + d type) were mostly restricted to the interior nodes of the network, which represented ancient haplotypes and geographically coincided with probable glacial refugia in southern Europe, agreed with a migrant-pool model. Evidence of a widespread pattern of polymorphism distribution indicated that mtDNA haplotypes were likely to be more ancient than the cpDNA haplotypes. Lineage sorting, due to relative age of cpDNA vs. mtDNA, plus the specific migratory mode, which recruited colonists from a random sample of resource populations during glacial expansion (thereby extending the lineage sorting period, LSP), may have resulted in the disassociation of chloroplast and mitochondrial genomes in oaks. PMID- 11195344 TI - Chromosome structure of Triticum timopheevii relative to T. turgidum. AB - The chromosome structure of four different wild populations and a cultivated line of Triticum timopheevii (2n = 28, AtAtGG) relative to Triticum turgidum (2n = 28, AABB) was studied, using genomic in situ hybridisation (GISH) and C-banding analysis of meiotic configurations in interspecific hybrids. Two wild accessions and the cultivated line showed the standard C-banding karyotype. The other two accessions are homozygous for translocation 5At/3G and translocations 1G/2G and 5G/6G. GISH analysis revealed that all the T. timopheevii accessions carry intergenome translocations 6At/1G and 1G/4G and identified the position of the breakpoint in translocation 5At/3G. C-banding analysis of pairing at metaphase I in the hybrids with T. turgidum provides evidence that four species-specific translocations (6AtS/1GS, 1GS/4GS, 4GS/4AtL, and 4AtL/3AtL) exist in T. timopheevii, and that T. timopheevii and T. turgidum differ in the pericentric inversion of chromosome 4A. Bridge plus acentric fragment configurations involving 4AL and 4AtL were identified in cells at anaphase I. This result suggests that the paracentric inversion of 4AL from T. turgidum does not exist in T. timopheevii. Both tetraploid species have undergone independent and distinct evolutionary chromosomal rearrangements. The position, intercalary or subdistal, of the breakpoints in species-specific translocations and inversions contrasts with the position, at or close to the centromere, of intraspecific translocations. Different mechanisms for intraspecific and species-specific chromosome rearrangements are suggested. PMID- 11195345 TI - Linkage mapping and nucleotide polymorphisms of the 6-SFT gene of cool-season grasses. AB - Fructan plays an important role as an alternate carbohydrate and may contribute to drought and cold-stress tolerances in various plant species. The gene coding for sucrose:fructan 6-fructosyltransferase (6-SFT; EC 2.4.1.10), an enzyme that catalyzes the formation and extension of beta-2,6-linked fructans (levans), is important to fructan synthesis in many cool-season grasses, including cereal species. In this study, we compared a conserved sequence from the 6-SFT gene in barley with comparable sequences in 20 other cool-season grasses. We detected several DNA length polymorphisms, including variations in one simple-sequence repeat (SSR) in a 6-SFT intron of the barley cultivars Steptoe and Morex. Using the 'Steptoe' x 'Morex' doubled-haploid mapping population, the 6-SFT gene was genetically mapped to the distal region in the short arm of barley chromosome 1 (7H), where it is closely linked with trait locus Rpg1. Primers designed from other conserved regions of the barley 6-SFT gene successfully amplified 351- or 354-bp sequences of this gene from diverse cool season grass species. Sequence identities of the PCR products were greater than 80% among the 21 species. Phylogeny, as determined using these DNA sequences, is similar to that obtained from rDNA ITS sequences, and congruent with our current knowledge of genome relationships. PMID- 11195346 TI - Automictic parthenogenesis in the parasitoid Venturia canescens (Hymenoptera: Ichneumonidae) revisited. AB - Both arrhenotokous and thelytokous reproduction are known to occur in the parasitoid wasp Venturia canescens. The cytological mechanism of thelytoky was previously reported to involve the formation of a restitution metaphase after the reduction division, but the exact nature of the subsequent divisions, whether reductional or equational, remained unclear. We reinvestigated the cytological mechanisms in a thelytokous strain collected in France. Our observations confirm previous results, but an equational and not a reduction division was observed after restitution. This type of reproduction can be classified as central fusion automictic parthenogenesis. In two arrhenotokous strains the normal pattern of oogenesis and syngamy of Hymenoptera was observed. In addition, we used PCR amplification to show that thelytoky in V. canescens is not caused by Wolbachia bacteria. The results are discussed in relation to maintenance of heterozygosity and female sex. PMID- 11195347 TI - Organization of highly repeated sequences in surface-spread pachytene chromosomes of rye. AB - A method of preparing two-dimensional surface spreads of plant synaptonemal complexes (SCs) associated with fluorescence in situ hybridization (FISH) has been applied to analyze the location and organization of five different highly repeated DNA sequences in rye. Our observations indicate that, depending on the type of sequence, the chromatin displays different types of organization. Telomeric sequences were seen tightly associated with the SC while other repetitive DNA sequences were found to form loops that are associated with SCs only at their bases. On the contrary, the FISH signal of a centromeric satellite had a granular appearance, reflecting that the hybridization occurs only with parts of the chromatin loops. PMID- 11195348 TI - Reverse transcriptase can stabilize or destabilize the genome. AB - Telomeres, the eukaryotic chromosome termini, are deoxyribonucleoprotein structures that distinguish natural chromosome ends from broken DNA. In most organisms, telomeres are extended by a reverse transcriptase (RT) with an integrated RNA template, telomerase; in Drosophila melanogaster, however, telomere-specific retrotransposons, HeT-A and TART transpose specifically to chromosome ends. Whether telomeres are extended by a telomerase or by retrotransposons, an RT is a key component. RT has been studied extensively, both for its important role in converting RNA genomes to DNA, which has great evolutionary impact, and as a therapeutic target in human retroviral diseases. Here we discuss a few important aspects of RT usage during retrotransposition and telomere elongation. PMID- 11195349 TI - Structure, expression, and conserved physical linkage of mouse testicular cell adhesion molecule-1 (TCAM-1) gene. AB - Isolation and characterization were performed for cDNA encoding mouse testicular cell adhesion molecule-1 (TCAM-1) using 2908 bases coding for a protein having 548 amino acids (60 kDa). Mouse TCAM-1 protein was found to consist of seven domains for signal sequence, five immunoglobulin (Ig) domains, and the transmembrane plus cytoplasmic domain. TCAM-1 gene and the region linking it to growth hormone (GH) gene located downstream from the TCAM-1 gene were then analyzed. The mouse TCAM-1 gene was 11.6 kb in length with 8 exons; the same as for the 12.0 kb rat gene. The distance from the TCAM-1 to GH gene was 12.5 kb in the mouse genome, and 7.6 kb in the rat. By Northern hybridization, 3.1-kb TCAM-1 mRNA was detected in 17-day testis and would appear present in pachytene spermatocytes and round spermatids. PMID- 11195350 TI - Simple sequence repeats in Cucumis mapping and map merging. AB - Thirty-four polymorphic simple-sequence repeats (SSRs) were evaluated for length polymorphism in melon (Cucumis melo L.) and cucumber (Cucumis sativus L.). SSR markers were located on three melon maps (18 on the map of 'Vedrantais' and PI 161375, 23 on the map of 'Piel de Sapo' and PI 161375, and 16 on the map of PI 414723 and 'Dulce'). In addition, 14 of the markers were located on the cucumber map of GY14 and PI 183967. SSRs proved to be randomly distributed throughout the melon and cucumber genomes. Mapping of the SSRs in the different maps led to the cross-identification of seven linkage groups in all melon maps. In addition, nine SSRs were common to both melon and cucumber maps. The potential of SSR markers as anchor points for melon-map merging and for comparative mapping with cucumber was demonstrated. PMID- 11195351 TI - Genetic variation and relationship among and within Withania species as revealed by AFLP markers. AB - Withania somnifera is an important medicinal plant, and its anticancerous properties have been attributed to various classes of withanolide compounds. The objective of the present study was to investigate the inter- and intraspecific genetic variation present in 35 individuals of W. somnifera and 5 individuals of W. coagulans using AFLP (amplified fragment length polymorphism) marker technique. The information about genetic variation determined from AFLP data for 40 individuals was employed to estimate similarity matrix value based on Jaccard's coefficient. The similarity values were further used to construct a phenetic dendrogram revealing the genetic relationships. The dendrogram generated by UPGMA (unweighted pair group method of arithmetic averages) distinguished W. somnifera from W. coagulans and formed two major clusters. These two main clusters shared a similarity coefficient of 0.3, correlating with the high level of polymorphism detected. The dendrogram further separated W. somnifera into three subclasses corresponding to Kashmiri and Nagori groups and an intermediate type. The AFLP profile of Kashmiri individuals was distinct from that of the Nagori group of plants. The intermediate genotype was distinct as it shared bands with both the Kashmiri and Nagori individuals, even though it was identified as a Kashmiri morphotype. Furthermore, the intermediate type shared a similarity coefficient of 0.8 with the Kashmiri individuals. The present work revealed low levels of variation within a population though high levels of polymorphism were detected between Nagori and Kashmiri populations. The ability of AFLP markers for efficient and rapid detection of genetic variations at the species as well as intraspecific level qualifies it as an efficient tool for estimating genetic similarity in plant species and effective management of genetic resources. PMID- 11195352 TI - In vitro binding of cattle PstI SINE with a 33-kDa nuclear protein. AB - A PstI family of SINEs (short interspersed elements) has been identified in some of the members of the family Bovidae, for example, cattle, buffalo and goat. In vitro DNA-protein interactions were studied to provide a better understanding of the function of these SINEs in the genome. Use of one such cattle PstI interspersed repeat sequence, as a probe in gel retardation assays, has lead to the identification of a repeat DNA-binding factor PIRBP (PstI interspersed repeat binding protein) from cattle liver nuclear extract. Southwestern analysis with liver nuclear extracts from cattle, goat, and buffalo revealed the presence of a PIRBP-like nuclear factor in all three species belonging to the family Bovidae. Deletion analysis localized the PIRBP binding site to an 80-bp (337-417 bp) region within the cattle PstI sequence. UV crosslinking and Southwestern analyses clearly indicated that PIRBP is a singular, small polypeptide of 33-kDa molecular mass. Homology search of the nucleic acids database revealed that the cattle PstI sequence was associated with many different genes of the family Bovidae, either in the 5' flanking region, 5' locus activating region, 3' UTR or in intervening sequences. The binding of the cattle PstI SINE by PIRBP and its association with the regulatory regions of the genes suggests that it plays an important role in the bovine genome. PMID- 11195353 TI - An integrated SSR and RFLP linkage map of Sorghum bicolor (L.) Moench. AB - We report the development, testing, and use (for genetic mapping) of a large number of polymerase chain reaction (PCR) primer sets that amplify DNA simple sequence repeat (SSR) loci of Sorghum bicolor (L.) Moench. Most of the primer sets were developed from clones isolated from two sorghum bacterial artificial chromosome (BAC) libraries and three enriched sorghum genomic-DNA (gDNA) libraries. A few were developed from sorghum DNA sequences present in public databases. The libraries were probed with radiolabeled di- and trinucleotide oligomers, the BAC libraries with four and six oligomers, respectively, and the enriched gDNA libraries with four and three oligomers, respectively. Both types of libraries were markedly enriched for SSRs relative to a size-fractionated gDNA library studied earlier. However, only 2% of the sequenced clones obtained from the size-fractionated gDNA library lacked a SSR, whereas 13% and 17% of the sequenced clones obtained from the BAC and enriched gDNA libraries, respectively, lacked a SSR. Primer sets were produced for 313 SSR loci. Two-hundred sixty-six (85%) of the loci were amplified and 165 (53%) of the loci were found to be polymorphic in a population composed of 18 diverse sorghum lines. (AG/TC)n and (AC/TG)n repeats comprised 91% of the dinucleotide SSRs and 52% of all of the SSRs at the polymorphic loci, whereas four types of repeats comprised 66% of the trinucleotide SSRs at the loci. Primer sequences are reported for the 165 polymorphic loci and for eight monomorphic loci that have a high degree of homology to genes. Also reported are the genetic map locations of 113 novel SSR loci (including four SSR-containing gene loci) and a linkage map composed of 147 SSR loci and 323 RFLP (restriction fragment length polymorphism) loci. The number of SSR loci per linkage group ranges from 8 to 30. The SSR loci are distributed relatively evenly throughout approximately 75% of the 1406-cM linkage map, but segments of five linkage groups comprising about 25% of the map either lack or contain few SSR loci. Mapping of SSR loci isolated from BAC clones located to these segments is likely to be the most efficient method for placing SSR loci in the segments. PMID- 11195354 TI - Positive meaning in amputation and thoughts about the amputated limb. AB - The majority of research conducted on the aftermath of amputation understandably concerns itself with its most distressing aspects. This research aimed to explore whether and how people think about their amputated limb, and whether and if they considered anything good had emerged from their amputation. One hundred and four (104) people completed the Trinity Amputation and Prosthesis Experience Scales (TAPES) and two open-ended questions. The majority of participants were young and had traumatic amputations. Fifty-six percent (56%) of people thought about their amputated limb. People with bilateral or a trans-femoral amputation were more likely to think about their amputated limb than people with a trans-tibial amputation. Forty-eight percent (48%) considered that something good had happened as a result of the amputation. Furthermore, finding positive meaning was significantly associated with more favourable physical capabilities and health ratings, lower levels of Athletic Activity Restriction and higher levels of Adjustment to Limitation. Future research and clinical implications are discussed. PMID- 11195355 TI - Prosthetic foot roll-over shapes with implications for alignment of trans-tibial prostheses. AB - Roll-over shape is introduced as a significant characteristic of prosthetic feet. The roll-over shapes of the Flexwalk, Quantum, SACH, and SAFE prosthetic feet were determined using three methods; two involving quasi-static loading and one dynamic loading. The results show that foot roll-over shape properties obtained by quasi-static and by dynamic methods are similar. Relationships between foot roll-over shape and the alignment of trans-tibial prostheses are introduced that suggest ways to align trans-tibial prostheses without walking trials and iterations. The relationships may explain what prosthetists attempt to accomplish when they dynamically align a trans-tibial limb. They also explain why prosthetic feet with different mechanical properties usually necessitate different alignments, and may explain why a number of gait studies of trans-tibial amputees do not show major gait differences when walking is executed on various kinds of prosthetic feet. PMID- 11195356 TI - Trans-tibial amputee gait: time-distance parameters and EMG activity. AB - Gait analysis of trans-tibial (TT) amputees discloses asymmetries in gait parameters between the amputated and sound legs. The present study aimed at outlining differences between both legs with regard to kinematic parameters and activity of the muscles controlling the knees. The gait of 14 traumatic TT amputees, walking at a mean speed of 74.96 m/min, was analysed by means of an electronic walkway, video camera, and portable electromyography system. Results showed differences in kinematic parameters. Step length, step time and swing time were significantly longer, while stance time and single support time were significantly shorter on the amputated side. A significant difference was also found between knee angle in both legs at heel strike. The biceps femoris/vastus medialis ratio in the amputated leg, during the first half of stance phase, was significantly higher when compared to the same muscle ratio in the sound leg. This difference was due to the higher activity of the biceps femoris, almost four times higher than the vastus medialis in the amputated leg. The observed differences in time-distance parameters are due to stiffness of the prosthesis ankle (the SACH foot) that impedes the normal forward advance of the amputated leg during the first half of stance. The higher knee flexion at heel strike is due to the necessary socket alignment. Unlike in the sound leg, the biceps femoris in the amputated leg reaches maximal activity during the first half of stance, cocontracting with the vastus medialis, to support body weight on the amputated leg. The obtained data can serve as a future reference for evaluating the influence of new prosthetic components on the quality of TT amputee's gait. PMID- 11195357 TI - Isokinetic strength and endurance of the knee extensors and flexors in trans tibial amputees. AB - Significant levels of muscular fatigue alter the co-ordination patterns and the ability to accomplish proper daily functions, especially in patients with initial low levels of strength. The purpose of this study was to evaluate the strength and endurance of the quadriceps and hamstring muscles in trans-tibial amputees. Concentric strength and endurance of the thigh muscles were measured bilaterally by an isokinetic dynamometer. The measured variables were torque and angle. For the endurance test, a fatigue index was calculated. Peak torque for extension and flexion was significantly higher in the sound limb (p<0.01). The fatigue index for extension was not significantly different in the sound limb from the amputated limb. The fatigue index for flexion is significantly higher in the sound limb (p<0.01). The finding may imply that from a metabolic point of view, the muscles of the amputated limb function properly. It is of great importance to reduce the bilateral deficit and the degree of atrophy as soon as possible in order to improve the level of performance. By choosing a correct strength and endurance training programme, one may expect to get a significant and good reaction from the muscles of the amputated limb as is expected from training the muscles of a sound limb. PMID- 11195358 TI - Ultrasound study of the motion of the residual femur within a trans-femoral socket during gait. AB - This study analyses the motion of the residual femur within a trans-femoral socket during gait using ultrasound data from two simultaneously transmitting transducers connected to two ultrasound scanners. Calibration tests accurately established the orientation of the two transducers mounted on the lateral wall of the socket. Relative positions of the ultrasound image of the femur were measured on video playback. Motion of the residual femur, relative to the lateral wall of the socket, at any instant during gait may be estimated, if the relative positions of the two transducers and the motion of the ultrasound image are known. A consistent pattern of femoral motion during 10 gait cycles is displayed graphically. The femoral motion in this paper is expressed as abduction/adduction or flexion/extension relative to the socket. However, without a full gait analysis study, the orientation of the socket relative to the ground or relative to the pelvis cannot be determined. Only one ultrasound scanner may be available for clinical use. Hence data collection may be restricted to only one transducer during gait. In order to simulate the single transducer mode, the ultrasound data recorded during the 10 previous gait cycles, was averaged at any instant of the gait cycle. The angular orientation of the femur was calculated based on the averaged data. Similar patterns of femoral motion were obtained irrespective of the technique adopted. PMID- 11195359 TI - A rear support walking frame for severely disabled children with cerebral palsy: initial development. AB - Ambulation for patients with total body involved cerebral palsy poses greater problems than those encountered in providing reciprocal walking for thoracic lesion paraplegic subjects. Experience with a prototype system showed that an orthosis which controls the movement of the lower limbs, in combination with a walking frame giving anterior support, enables such patients to walk. Despite shortcomings which restricted the use of the system to an indoor environment it provided a sound basis on which to examine walking frames to address the problems which had been identified. A review of these devices showed that the most effective means of achieving this aim is the use of a wheeled walking frame which provides vertical support and truncal alignment via a sprung pantograph mounted to the rear of the patient (rear support walking frames). Trials were conducted with two existing rear support walking frames. These indicated their potential for severely disabled patients, but also identified the need for higher stiffness in the structure and more sensitive control of vertical support to be achieved if effective ambulation in a wider range of environments was to be made possible for the target group. Prototypes based on an existing frame, which took account of the specification requirements, were produced for four new total body involved cerebral palsy patients with the same degree of walking dysfunction. Three of the patients were able to walk in a much wider variety of environments than any patient in the original system. A number of other issues related to transfer and steering were identified as requiring further development. PMID- 11195360 TI - Principal structural testing of trans-tibial prosthetic assemblies: specimen preparation. AB - A simple alignment apparatus and the method of transferring the offset test load to the prosthetic assembly through an aligned mandrel for the principal structural tests in accordance with ISO 10328 is presented. The new alignment apparatus was used to prepare test specimens consisting of traditional laminated prosthetic sockets, adaptors, shanks and foot blocks. The alignment apparatus proved useful in ensuring proper orientation and positioning of the components relative to one another as well as to the loading coordinate axes. The sockets and the other components achieved the maximum load specifications during the static failure tests and no failure of components was observed in the cyclic tests. PMID- 11195361 TI - Combined shock-absorbing shin and dynamic response. PMID- 11195362 TI - Fitting of electronic elbow on an elbow disarticulated patient by means of a new surgical technique. AB - Rehabilitation of trans-humeral amputees represents a challenge. One of the difficulties to overcome is prosthetic suspension. In the case of elbow disarticulation the presence of humeral condyles permits better suspension, but there is no room for elbow joints, particularly electronic ones, and the only available mechanisms are provided by external hinges. The purpose of this report is to present a case of a primarily elbow disarticulated patient, with indication for surgical revision due to bad skin coverage, neuroma and the wish to improve prosthetic fitting. The surgical plan outlined was to produce a shortening of the humerus, by means of an osteotomy just above the humeral condyles, preserving them for prosthetic suspension. This bone reduction was carried out with complementary shaping of bone segments with an indentation to enhance fixation. The operation was completed with neuroma resection, myodesis and removal of the skin grafted area. Preservation of the humeral condyles actually produced effective suspension. For final fitting a Utah Arm II was used, with wrist rotator, and interchangeable hand and Greifer for terminal devices. Good initial results and at nine months follow-up suggest this procedure should be considered in other elective situations. PMID- 11195364 TI - On being an Inorganic Chemistry Janus: looking back with thanks and ahead with excitement. PMID- 11195363 TI - A myoelectrically controlled shoulder-elbow orthosis for unrecovered brachial plexus injury. AB - Two myoelectrically controlled battery powered shoulder-elbow orthoses manufactured individually for two traumatic unilateral brachial plexus injury cases are reported. The first case was 24 years old and the other was 6 years old. Both patients had undergone unsuccessful microsurgical nerve repair procedures leaving them with elbow and shoulder paralysis and some residual hand motion. Manufactured orthoses were made of lightweight thermoplastic polyethylene. They stabilised the affected shoulder joint in the neutral position. Elbow extension and flexion were activated by a myoelectrically controlled battery powered orthosis, and the active range of motion of the elbow was between 60 and 140 degrees. These orthoses achieved elbow motions at a speed of 16 degrees per second. The rehabilitation time was 3 months in both patients. The older patient was rehabilitated using a 1 kg mass, and the younger one with 0.5 kg mass, throughout the full range of active elbow motions. After 21 months it was found, in both cases, that the orthotic treatment had been successful and that the patients had been given the ability to engage in two-handed activities of daily living. PMID- 11195365 TI - Si extraction from silica in a basic polychalcogenide flux. Stabilization of Ba4SiSb2Se11, a novel mixed selenosilicate/selenoantimonate with a polar structure. AB - An unusual compound, Ba4SiSb2Se11, was discovered from a reaction of Ba/Th/Sb/Se. It is assumed that Si was extracted from the silica reaction tube. It forms as silver needlelike crystals in the polar space group Cmc2(1) with a = 9.3981(3) A, b = 25.7192(7) A, c = 8.7748(3) A, and Z = 4. A rational synthesis has been devised at 600 degrees C. The compound is composed of Ba2+ ions stabilized between infinite one-dimensional [SiSb2Se11]8- chains running parallel to the a axis. Each chain is composed of a [SbSe2]- infinity backbone with [SiSe4]4- tetrahedra chelating every other Sb atom from the same side of the backbone. The V-shaped triselenide groups, (Se3)2-, are attached to the rest of the Sb atoms in the chain through one of their terminal Se atoms. The compound has a band gap of 1.43 eV. The Raman spectrum shows a broad shift at 247 cm-1 and a shoulder around 234 cm-1, which are related to the Se-Se vibration of the triselenide groups and/or the Si-Se vibrations of the [SiSe4]4- groups. The compound decomposes at 522 degrees C. PMID- 11195366 TI - Preparations, characterizations, and structures of (biimidazole)dihalobis(triphenylphosphine)rhenium(III) salts: strong ion-pairing and acid-base properties. AB - Two-electron reduction occurs when the Re(V) precursors ReOX3(PPh3)2 and ReO(OEt)X2(PPh3)2 are reacted with biimidazole (biimH2) in boiling chloroform, affording rhenium(III) cationic complexes of the type cis,trans [ReX2(PPh3)2(biimH2)]X with X = Cl, Br, and I. Crystal structures are determined for the compounds with the three halogens, as well as for the [ReCl2(PPh3)2(biimH2)](benzoate) salt. In all cases, the counterion is attached to the complex cation via hydrogen bonding with the N-H groups of coordinated biimidazole. Variable-temperature 1H NMR spectroscopy shows that a mixture of [ReCl2(PPh3)2(biimH2)](benzoate) and [ReCl2(PPh3)2(biimH2)]Cl is in slow exchange below -50 degrees C in CD2Cl2, indicating that ion pairing is retained in solution. Both N-H groups can be deprotonated with sodium methoxide, and their acidities are evaluated from UV-visible spectra. Competition between monodeprotonated [ReCl2(PPh3)2(biimH)] and various carboxylic acids reveals that the acidity of the first N-H proton corresponds to that of acetic acid (pKa(aq) approximately 4.8). By a similar competitive reaction between bis-deprotonated [ReCl2(PPh3)2(biim)]- and phenols, the second acidity is estimated to be close to that of phenol (pKa(aq) approximately 9.8). PMID- 11195367 TI - Structural and electronic properties of Co-corrole, Co-corrin, and Co-porphyrin. AB - A quantitative study of the structure and electronic properties of Co-corrole, Co corrin, and Co-porphyrin, using density functional theory, is reported. The structure of each macrocycle is optimized, with no symmetry constraints, by considering different spin states. The ground-state structures and spin states (S = 1 for Co-corrole, S = 0 for Co-corrin and S = 1/2 for Co-porphyrin) are in good agreement with the experimental data available. The trends in the sizes of the coordination cavities upon varying the inner metal atom and/or the macrocycle are analyzed and compared with those for the Fe-porphyrin we studied previously. Our results reveal that most of the distortion of the Co-corrin core in the B12 coenzyme is due to the inherent properties of Co-corrin. Quite different behaviors are found between corrinoids and porphyrins upon varying the spin state. While an increase in the metal-nitrogen (M-N) distance with spin state occurs in the porphyrins, the corrinoids show little variation in the M-N distance and, in some cases, undergo small structural changes in the ring structure. These results aid in understanding the often discussed question of why nature has chosen corrin/porphyrin for carrying out the particular biological functions identified in the B12 coenzyme. PMID- 11195368 TI - Molecule-based magnets formed by bimetallic three-dimensional oxalate networks and chiral tris(bipyridyl) complex cations. The series [ZII(bpy)3][ClO4][MIICrIII(ox)3] (ZII = Ru, Fe, Co, and Ni; MII = Mn, Fe, Co, Ni, Cu, and Zn; ox = oxalate dianion). AB - The synthesis, structure, and physical properties of the series of molecular magnets formulated as [ZII(bpy)3][ClO4][MIICrIII(ox)3] (ZII = Ru, Fe, Co, and Ni; MII = Mn, Fe, Co, Ni, Cu, and Zn; ox = oxalate dianion) are presented. All the compounds are isostructural to the [Ru(bpy)3][ClO4][MnCr(ox)3] member whose structure (cubic space group P4(1)32 with a = 15.506(2) A, Z = 4) consists of a three-dimensional bimetallic network formed by alternating MII and CrIII ions connected by oxalate anions. The identical chirality (lambda in the solved crystal) of all the metallic centers determines the 3D chiral structure adopted by these compounds. The anionic 3D sublattice leaves some holes where the chiral [Z(bpy)3]2+ and ClO4- counterions are located. These compounds behave as soft ferromagnets with ordering temperatures up to 6.6 K and coercive fields up to 8 mT. PMID- 11195369 TI - Lithium amidohydridoaluminates. AB - The amidohydridometalates [Li(THF)4][HAl(NPh2)3] (1), [Li(DME)3][HAl(N(CH2Ph)2)3] (2), and [((THF)3Li)-(H2Al(NcHex2)2)].0.5toluene (3.0.5toluene; cHex = C6H11) have been prepared by reaction of the corresponding amines with LiAlH4 in THF. For 2 recrystallization from DME is required to obtain crystals, suitable for X ray diffraction. The new compounds have been characterized by elemental analyses, IR, NMR, and MS techniques, and X-ray structure analyses. According to this the anions of 1, 2, and 3x0.5toluene possess distorted tetrahedral coordination spheres. In 3x0.5toluene a Li...H contact of 184(4) pm was detected to complete the tetrahedral coordination of the Li+ center. PMID- 11195370 TI - Synthesis, characterization, solid-state molecular structures, and deprotonation reactions of cationic alcohol complexes of osmium nitrosyl porphyrins. AB - New alkoxide (OEP)Os(NO)(OR) (OEP = 2,3,7,8,12,13,17,18-octaethylporphyrinato dianion; R = ethyl, isopropyl, hexyl, cyclohexyl) compounds and alcohol [(OEP)Os(NO)(HOR)]+ complexes (R = methyl, ethyl, isopropyl, hexyl, cyclohexyl) have been prepared in high yields and have been fully characterized by IR, 1H NMR, and UV-vis spectroscopy, and by elemental analyses. The (OEP)Os(NO)(OEt) compound was characterized by single-crystal X-ray crystallography. The cationic aqua and alcohol [(OEP)Os(NO)(HOR)]+ complexes (R = ethyl, isopropyl, hexyl) complexes were also characterized by single-crystal X-ray crystallography, and the latter represent the first osmium alcohol structures to be reported. The electrophilic [(OEP)Os(NO)]+ cation in the [(OEP)Os(NO)(HOR)]+ complexes renders the coordinated alcohol ligands susceptible to deprotonation by pyridine to produce the corresponding alkoxide (OEP)Os(NO)(OR) derivatives. A one-pot reaction sequence for the preparation of new (OEP)Os(NO)(OR) complexes from (OEP)Os(NO)(OEt) was developed, which was based on (i) initial protonation of the ethoxide compound to give [(OEP)Os(NO)(HOEt)]+, (ii) alcohol substitution by ROH to give [(OEP)Os(NO)(HOR)]+, and (iii) deprotonation of the latter by pyridine to give (OEP)Os(NO)(OR). PMID- 11195371 TI - Biphasic behavior of the high-spin-->low-spin relaxation of [Fe(btpa)](PF6)2 in solution (btpa = N,N,N',N'-tetrakis(2-pyridylmethyl)-6,6'-bis(aminomethyl)-2,2'- bipyridine). AB - The light-induced high-spin-->low-spin relaxation for the Fe(II) spin-crossover compounds [Fe(btpa)](PF6)2 and [Fe(b(bdpa))](PF6)2 in solution, where btpa is the potentially octadentate ligand N,N,N',N'-tetrakis(2-pyridylmethyl)-6,6' bis(aminomethyl)-2,2'-bipyridine and b(bdpa) is the analogous hexadentate ligand N,N'-bis(benzyl)-N,N'-bis(2-pyridylmethyl)-6,6'-bis(aminomethyl)-2,2'- bipyridine, respectively, has been studied by temperature-dependent laser flash photolysis. [Fe(b(bdpa))](PF6)2 shows single-exponential 5T2-->1A1 relaxation kinetics, whereas [Fe(btpa)](PF6)2 exhibits solvent-independent biphasic relaxation kinetics. The fast process of [Fe(btpa)](PF6)2 with a rate constant, kHL, of 2.5 x 10(7) s-1 at 295 K and an activation energy, Ea, of 1294(26) cm-1 in methanol can be assigned to the 5T2-->1A1 relaxation as well. The slow process with a kHL(295 K) of 3.7 x 10(5) s-1 and a Ea of 2297(32) cm-1 in methanol--which is the slowest light-induced relaxation process observed so far for an Fe(II) spin-crossover complex in solution--is assigned to a coupling of the 5T2-->1A1 relaxation process to a geometrical rearrangement within the pendent pyridyl arms. PMID- 11195372 TI - Heteroleptic lanthanide compounds with chalcogenolate ligands: reduction of PhNNPh/PhEEPh (E = Se or Te) mixtures with Ln (Ln = Ho, Er, Tm, Yb). Thermolysis can give LnN or LnE. AB - Lanthanide metals reduce mixtures of azobenzene and PhEEPh (E = Se or Te) in pyridine to give the bimetallic compounds [(py)2Ln(EPh)(PhNNPh)]2 (E = Se, Ln = Ho (1), Er (2), Tm (3), Yb (4); E = Te, Ln = Ho (5), Er (6), Tm (7), Yb (8)). The structures of [(py)2Er(mu-eta 2-eta 2-PhNNPh)(SePh)](2).2py (2) and [(py)2Ho(mu eta 2-eta 2-PhNNPh)(TePh)](2).2py (5) have been determined by low-temperature single-crystal X-ray diffraction, and the nearly identical unit cell volumes of the remaining compounds indicate they are most likely isomorphous to 2 or 5. In all compounds, the Ln(III) ions are bridged by a pair of mu-eta 2-eta 2-PhNNPh ligands that, from the N-N bond length, have clearly been reduced to dianions. Charge is balanced by the single terminal EPh ligand on each Ln, and the coordination sphere is saturated by two pyridine donors to give seven coordinate metal centers. Thermal decomposition of 5 gives HoTe, 8 gives a mixture of YbN and YbTe, and 1 does not give a crystalline solid-state product. Crystal data (Mo K alpha, 153(2) K) are as follows: 2, monoclinic group P2(1)/n, a = 11.864(3) A, b = 14.188(2) A, c = 17.624(2) A, beta = 91.62(2) degrees, V = 2965(1) A3, Z = 4; 5, triclinic space group P1, a = 10.349(2) A, b = 17.662(4) A, c = 17.730(8) A, alpha = 75.82(3) degrees, beta = 74.11(3) degrees, gamma = 89.45(2) degrees, V = 3016(2) A3, Z = 2. PMID- 11195373 TI - New molecular assemblies of redox isomers, [CrIII(X4SQ)3-n(X4Cat)n]-n (X = Cl and Br; n = 0, 1, and 2), with metallocenium cations, [MIIICp2]+ (M = Co and Fe): X ray crystal structures and physical properties. AB - A series of redox isomers of [CrIII(X4SQ)(X4Cat)2]2-, [CrIII(X4SQ)2(X4Cat)]-, and [CrIII(X4SQ)3]0 (X = Cl and Br, SQ = semiquinonate, and Cat = catecholate) have been synthesized and characterized as charge-transfer (CT) compounds with metallocenium cations: (CoIIICp2)2[CrIII(Cl4SQ)(Cl4Cat)2] (1), (CoIIICp2)2[CrIII(Br4SQ)(Br4Cat)2] (2), (FeIIICp2)[CrIII(Cl4SQ)2(Cl4Cat)].C6H6 (4), (FeIIICp2)[CrIII(Br4SQ)2(Br4Cat)].CS2 (5), and (FeIIICp2)[CrIII(Cl4SQ)2(Cl4Cat)][CrIII(Cl4SQ)3] (6). First, the oxidation states of the chromium complexes are strongly dependent on the redox potentials of the metallocenes used. The CoIICp2, exhibiting stronger reduction power than FeIICp2, is useful for two-electron reduction of the [CrIII(X4SQ)3]0, affording [CrIII(X4SQ)(X4Cat)2]2- (1 and 2), which are first isolated and crystallographically characterized in the solid state. In contrast the reaction with FeIICp2 affords only [CrIII(X4SQ)2(X4Cat)]- (4 and 5). Second, solvents influence crystal structures of these compounds. The solvent set of C6H6/CS2 gives 1:1:C6H6 compound 4 with unique charged anions, [CrIII(Cl4SQ)2(Cl4Cat)]-, while the other set, n-C6H12/CS2, affords 1:2 compound 6 including the two redox isomers, [CrIII(Cl4SQ)2(Cl4Cat)]- and [CrIII(Cl4SQ)3]0. The [CrIII(X4SQ)(X4Cat)2]2- anions in 1 and 2 show no significant interconnection between them (discrete type), while the [CrIII(X4SQ)2(X4Cat)]- anions in 4-6 show one-dimensional column-type structures with the aid of intermolecular stacking interactions of the ligand moieties. The anions in 4 show additional stacking interaction with the [FeIIICp2]+ to form one-dimensional ...[D][A][S][D][A]... (D = [FeIIICp2]+, A = [CrIII(Cl4SQ)2(Cl4Cat)]-, and S = C6H6) type mixed-stack arrangements similar to that of previously reported (CoIIICp2)[CrIII(Cl4SQ)2(Cl4Cat)].C6H6 (3). Compound 6 forms a two-dimensional sheet structure where the two redox isomers, [CrIII(Cl4SQ)2(Cl4Cat)]- and [CrIII(Cl4SQ)3]0, are included. The sheet is regarded as a mixed-valence molecular assembly. Two types of the anions, [CrIII(X4SQ)(X4Cat)2]2- (1 and 2) and [CrIII(X4SQ)2(X4Cat)]- (4-6), exhibiting an intramolecular mixed-valence state, show intramolecular intervalence CT transition (IVCT) from the Cat to the SQ at near 5800 and 4300 cm-1, respectively, both in the solution and in the solid states. The intermolecular mixed-valence state of 6 was characterized by absorption spectroscopy, electric conductivity, and SQUID magnetometry. Interestingly, this mixed-valence state of the chromium module is dependent on the redox active nature of the coordinated ligands. PMID- 11195374 TI - Photon upconversion properties of Ni2+ in magnetic and nonmagnetic chloride host lattices. AB - Near-infrared to visible upconversion luminescence in Ni2+:CsCdCl3, Ni2+:CsMnCl3, and Ni2+:RbMnCl3 is presented and analyzed. In all three materials upconversion occurs via a sequence of ground-state absorption/excited-state absorption processes, which are both formally spin-forbidden transitions. Consequently, in the diamagnetic Ni2+:CsCdCl3 they are weak, and the efficiency of the upconversion process is relatively low. This is in clear contrast to the isostructural Ni2+:RbMnCl3 where the spin selection rule relaxes because of Ni(2+)-Mn2+ exchange interactions, leading to an intensity enhancement of the spin-flip transitions involved in the Ni2+ upconversion mechanism. This results in an exchange-induced enhancement of the upconversion rate in Ni2+:RbMnCl3 relative to Ni2+:CsCdCl3 by 2 orders of magnitude after two-color excitation into the maxima of the ground-state and excited-state absorption bands. In Ni2+:CsMnCl3 the Ni(2+)-Mn2+ exchange interaction does not play a significant role. This is due to the different Ni(2+)-Cl(-)-Mn2+ bridging geometry relative to Ni2+:RbMnCl3. In contrast to Ni2+:CsCdCl3 and Ni2+:RbMnCl3 where the upconversion luminescence occurs from Ni2+, in Ni2+:CsMnCl3 the upconverted energy is emitted from Mn2+ in the visible spectral region. This leads to an enhanced visible upconversion luminescence in Ni2+:CsMnCl3, relative to the other two samples where Ni2+ near-infrared inter-excited-state emissions compete with the visible upconversion luminescence. PMID- 11195375 TI - Copper(I) chemistry of bis(pyrazolyl)diphenylborate ligands: formation of a heterocycle by Cu-mediated acetonitrile addition. PMID- 11195376 TI - Synthesis and dehydrative condensation of monomeric hydroxoruthenium complexes with hydrotris(3,5-diisopropylpyrazolyl)borate ligand, TpiPr2Ru(L2)-OH (L2 = dppe, bipy). PMID- 11195377 TI - The molecular structure of (PSH+)(nido-7,8-C2B9H12-) determined by neutron diffraction (PS = proton sponge, 1,8-bis(dimethylamino)naphthalene). PMID- 11195378 TI - A NdIIICuII molecular material with a honeycomb-like structure. PMID- 11195379 TI - Mass and FTIR spectroscopic investigations of gaseous manganese tetrafluoride. PMID- 11195380 TI - Modeling the active sites of metalloenzymes. 4. Predictions of the unready states of [NiFe] Desulfovibrio gigas hydrogenase from density functional theory. AB - Density functional theory has been used to predict the structures of a variety of active site models for the unready states, Ni-A and Ni-SU, of the [NiFe] hydrogenase from Desulfovibrio gigas. By comparing available experimental results on Ni-A, Ni-SU, and Ni-SI with the computational results on these model complexes, we have been able to identify the most likely formulas and structures for the active sites of Ni-A and Ni-SU. Ni-A is predicted to be a Ni(III)-Fe(II) species with the bridging hydroxo ligand, rather than the expected oxo ligand, while Ni-SU is predicted to be a Ni(II)-Fe(II) species with a water molecule coordinated to the Fe center. Both have one of the terminal S atoms (cysteines) protonated. PMID- 11195381 TI - Synthesis and characterization of the diruthenium(III) complexes Ru2(F4Oap)2(F5ap)2 and Ru2(F4Oap)(F4NCNap)(F5ap)2 where F4Oap is the 2-(3,4,5,6 tetrafluoro-2-oxoanilino)pyridinate anion, F4NCNap is the 2-(3,4,5,6-tetrafluoro 2-cyanamidoanilino)pyridinate anion, and F5ap is the 2-(2,3,4,5,6 pentafluoroanilino)pyridinate anion. PMID- 11195382 TI - Preparation and crystal structure of tetraphenylphosphonium triiodotetrabromide [PPh4][I3Br4]. AB - Tetraphenylphosphonium triiodotetrabromide [PPh4][I3Br4] is obtained by the reaction of tetraphenylphosphonium bromide with iodine monobromide. It is the first example of an iodine rich, seven-membered polybromide. [PPh4][I3Br4] crystallizes triclinic in the space group P1 with a = 10.947(1) A, b = 11.945(1) A, c = 12.896(1) A, alpha = 66.80(1) degrees, beta = 77.21(1) degrees, gamma = 85.73(1) degrees, and two formula units per unit cell. The final R indices [I > 4 sigma(I)] are R1 = 0.0362 and wR2 = 0.0944. PMID- 11195383 TI - Hydrothermal syntheses, structures, and properties of [Cu3Cl2CN(pyrazine)] and copper(I) halide pyrazine polymers. AB - Crystals of copper halide and pseudohalide compounds with pyrazine are synthesized under hydrothermal conditions. The title compound, [Cu3Cl2CNPz] (1) (Pz = pyrazine), is a new copper compound exhibiting an unusual -(Cu3Cl2)- polymeric stair structural motif and three-coordinate cyanide. Compound 1 crystallizes in the monoclinic space group P2(1)/m, with a = 3.6530(7) A, b = 17.160(3) A, c = 6.9800(14) A, beta = 90.58(3) degrees, and Z = 2. In addition, the series of complexes [Cu2X2Pz] for X = Cl (2), Br (3), and I (4) are also crystallized under hydrothermal conditions. The inorganic polymer [Cu2Br2Pz] (3) belongs to the triclinic space group P1, with a = 6.9671(14) A, b = 7.849(2) A, c = 8.099(2) A, alpha = 71.69(3) degrees, beta = 70.71(3) degrees, gamma = 85.43(3) degrees, and Z = 2. The structure of 3, is similar to the recently reported structure for [Cu2Cl2Pz] (2) (Kawata, S.; Kitagawa, S.; Kumagai, H.; Iwabuchi, S.; Katada, M. Inorg. Chim. Acta 1998, 267, 143). The third member of the series, [Cu2I2Pz], is found to be isostructural on the basis of X-ray powder diffraction results. The lattice parameters are refined from indexed reflections to a = 7.115(10) A, b = 8.321(19) A, c = 8.378(17) A, alpha = 71.1(3) degrees, beta = 67.3(1) degrees, and gamma = 83.0(2) degrees. Electronic spectra show that compounds 1-4 have optical band gaps in the range 2.2-2.4 eV. The infrared and Raman spectra as well as the thermal properties of all compounds are presented. PMID- 11195384 TI - Crystal structure of CF3I(Cl)F. AB - In addition to CF3IF2 and CF3ICl2, CF3I(Cl)F is the only known example of the (trifluoromethyl)iodine dihalides. CF3I(Cl)F is even at low temperatures not stable in solution and decomposes by symmetrization. It crystallizes in the orthorhombic space group Cmca with a = 6.898(1) A, b = 7.310(1) A, c = 20.127(1) A and eight formula units per unit cell. The final R indices [I > 2 sigma(I)] are R1 = 0.0372 and wR2 = 0.0981. PMID- 11195386 TI - Synthesis of a vinylene-bridged ferrocene-hydroquinone complex and its unusual structural change originated by proton-coupled electron transfer. PMID- 11195385 TI - Mutual interdependence of spin crossover and metal-metal bond formation in M2Cl9(3-) (M = Fe, Ru, Os). AB - Broken-symmetry density functional theory is used to examine the coupling between metal ions in the face-shared bioctahedral complexes M2Cl9(3-), M = Fe, Ru, Os. In the ruthenium and osmium systems, the metal ions have low-spin configurations, and strong coupling results in the formation of a metal-metal sigma bond. In contrast, the iron system contains two weakly coupled high-spin FeIII centers, the different behavior being due to the high spin-polarization energy in the smaller Fe atom. At Fe-Fe separations shorter than 2.4 A, however, an abrupt transition occurs and the ground state becomes very similar to that for the heavier congeners (i.e., strongly coupled low-spin FeIII). The intrinsic link between high-spin/low-spin transitions on the individual metal centers and the onset of metal-metal bond formation is traced to the spin-polarization energy, which plays a central role in both processes. PMID- 11195387 TI - Structural characterization and magnetic properties of sandwich-type tungstoarsenate complexes. Study of a mixed-valent VIV2/VV heteropolyanion. AB - Complexes K11Na1[As2W18(Mn(H2O))3O66]x27H2O (1) and Na12[As2W18(Co(H2O))3O66]x34H2O (2) have been characterized. 1 crystallizes in the orthorhombic space group Pnma, with a = 30.6484(4) A, b = 14.9946(2) A, and c = 19.17080(10) A (Z = 4), while 2 crystallizes in the monoclinic space group C2/c, with a = 14.124(2) A, b = 23.294(3) A, c = 32.247(3) A, and beta = 98.935(10) degrees (Z = 4). Structures of the anions of 1 and 2 are similar, the divalent metals adopting a square pyramidal environment. K11[As2W18(VO)3O66]x23H2O (3) crystallizes in the orthorhombic space group Pnma, with a = 30.6240(5) A, b = 14.9861(2) A, and c = 19.2651(3) A (Z = 4). The structure has revealed a disorder on two of the three metals linking the [alpha AsW9O33]9- parts. For these two vanadium atoms, the V=O bonds are directed alternatively toward the inside or the outside of the [alpha-AsW9O33]9- cavity. The remaining vanadium shows a V=O bond always directed toward the outside of the cavity. Titration of VIV by CeIV revealed that 3 is the mixed-valent VIV2VV species. Magnetic measurements are in agreement with this formulation. The high temperature molar magnetic susceptibility of a powdered sample of 3 clearly confirms the presence of two d1 centers. The two VIV are antiferromagnetically coupled, with J = -2.9 cm-1 and g = 1.93. Crystallographic data do not permit the location of the two VIV to be distinguished from the location of the VV. As expected, the Mn(II) are very weakly antiferromagnetically coupled in compound 1. The complex Na8[Ni(H2O)6]2[As2W18(Ni(H2O))3O66]x20H2O (4) has been synthesized. The anion crystallized with two octahedral [Ni(H2O)6]2+ as counterions. Magnetic data have been fitted assuming that the only exchange-coupled centers are the nickels of the polyanion. 4 exhibits an antiferromagnetic coupling with J = -1.7 cm-1, g = 2.27, and theta = -1.5 K. PMID- 11195388 TI - Aqueous solution speciation of Fe(III) complexes with dihydroxamate siderophores alcaligin and rhodotorulic acid and synthetic analogues using electrospray ionization mass spectrometry. AB - Aqueous solutions of Fe3+ complexes of cyclic (alcaligin) and linear (rhodotorulic acid) dihydroxamate siderophores and synthetic linear eight-carbon chain and two-carbon-chain dihydroxamic acids ([CH3N(OH)C=O)]2(CH2)n; H2Ln; n = 2 and 8) were investigated by electrospray ionization mass spectrometry (ESI-MS). Information was obtained relevant to the structure and the speciation of various Fe(III)-dihydroxamate complexes present in aqueous solution by (1) comparing different ionization techniques (ESI and FAB), (2) altering the experimental parameters (Fe3+/ligand ratio, pH, cone voltage), (3) using high-stability hexacoordinated Fe(III) siderophore complex mixtures (ferrioxamine B/ferrioxamine E) as a calibrant to quantify intrinsically neutral (H+ clustered or protonated) and intrinsically charged complexes, and (4) using mixed-metal complexes containing Fe3+, Ga3+, and Al3+. These results illustrate that for all dihydroxamic acid ligands investigated multiple tris- and bis-chelated mono- and di-Fe(III) species are present in relative concentrations that depend on the pH and Fe/L ratio. PMID- 11195389 TI - Synthesis and characterization of novel trigonal bipyramidal technetium(III) mixed-ligand complexes with SES/S/P coordination (E = O, N(CH3), S). AB - Five-coordinate oxotechnetium(V) mixed-ligand complexes [TcO(SES)(S-p-C6H4-OMe)], where SES is a tridentate dithiolato fragment of the type -S(CH2)2E(CH2)2S- (E = O, 1; E = S, 2; E = NMe, 3) are converted via reduction-substitution reactions in the presence of PMe2Ph into the corresponding five-coordinate Tc(III) complexes [Tc(SES)(S-p-C6H4-OMe)(PMe2Ph)] (E = O, 4; E = S, 5; E = NMe, 6). Rearrangement of the original square pyramidal "3 + 1" oxo species to the trigonal bipyramidal "3 + 1 + 1" Tc(III) complexes occurs by placing the three thiolate donors on the basal plane, the phosphine phosphorus, and the heteroatom of the tridentate ligand at the apexes of the bipyramid. These Tc(III) complexes are diamagnetic species, thereby allowing multinuclear NMR characterization in solution, which confirm their structures to be identical to those observed in the solid state via X-ray determinations. PMID- 11195390 TI - Extended X-ray absorption fine structure analysis of the bipyridine copper complexes in atom transfer radical polymerization. PMID- 11195391 TI - Electrochemical synthesis and structural and physical characterization of one- and two-electron-reduced forms of [SMo12O40]2-. AB - Isolation of a soluble [NHex4]+ salt has allowed a detailed electrochemical study of the anion alpha-[SMo12O40]2- to be undertaken. Four reversible one-electron reduction processes are observed in CH2Cl2 solution. Controlled potential electrolysis led to isolation of tetraalkylammonium salts of the one-electron reduced anion alpha-[SMo12O40]3- and the two-electron-reduced anion alpha [SMo12O40].4- [SMo12O40]3- is stable to disproportionation in dry solvents (Kdis = 10(-7.4). EPR and magnetic susceptibility data indicate that [SMo12O40]3- is a simple paramagnet (S = 1/2) while [SMo12O40]4- is paramagnetic with the mu eff values decreasing at low temperatures. Solutions of the two-electron-reduced species are EPR silent, but microcrystalline powders show very weak signals. The crystal structure of alpha-[NBu4]3[SMo12O40] has been determined (triclinic P1; a = 13.840(3) A; b = 15.587(4) A; c = 19.370(3) A; alpha = 94.82(2) degrees; beta = 93.10(1) degrees; gamma = 91.05(2) degrees; Z = 2). There is disorder around the C2 axis of the central SO4(2-) tetrahedron. In the presence of aqueous HClO4 (0.045 M) in thf/H2O or MeCN/H2O (98/2 v/v), [SMo12O40]2- exhibits five two electron-reduction processes. Under these conditions, [SMo12O40]3- protonates and disproportionates into [SMo12O40]2- and the (2e-, 2H+)-reduced anion [H2SMo12O40]2-. PMID- 11195392 TI - Synthesis of nickel sulfides in aqueous solutions using sodium dithionite. AB - Reaction of nickel chloride with sodium dithionite in aqueous solutions at ambient temperature has been investigated systematically to obtain nickel sulfides. The products are characterized by X-ray diffraction, thermogravimetric analysis, and electrical resistivity and magnetic susceptibility measurements. It is found that the compositions and structures of the products are controlled by the reaction pH and the amount of the reactants. While reactions under highly acidic (pH < or = 2) and basic (pH > or = 7) conditions yield crystalline sulfur and amorphous or poorly crystalline NiySx, respectively, those at intermediate 3 < or = pH < or = 6 give crystalline NiySx. Both crystalline Ni3S2 (heazlewoodite structure) and Ni3S4 (spinel structure) have been obtained at room temperature. Additionally, NiS (millerite structure) is obtained by carefully heating Ni3S4 at 200 degrees C in a mixture of 90% Ar and 10% H2. Ni3S4 is found to be metastable, and it begins to disproportionate above 100 degrees C. Both Ni3S2 and Ni3S4 show metallic behavior. While Ni3S2 exhibits temperature-independent magnetic susceptibility, Ni3S4 shows ferrimagnetic ordering below 20 K. PMID- 11195393 TI - EPR spectroscopic studies of the reduction of chromium(VI) by methanol in the presence of peptides. Formation of long-lived chromium(V) peptide complexes. AB - The synthesis and characterization of the first Cr(V) complexes with non-sulfur containing peptides, which may mimic the chemistry of the intermediates in the formation of Cr-induced peptide-DNA cross-links in vivo, are reported. The reduction of Cr(VI) with methanol in the presence of a number of non-sulfur containing peptides produced relatively stable Cr(V)-peptide complexes, which were characterized by EPR spectroscopy and electrospray mass spectrometry. The reaction of Cr(VI) with methanol alone (in the absence of peptide ligands) resulted in the formation of two Cr(V)-methanol intermediates, with giso values of 1.9765 and 1.9687. The methanol reduction of Cr(VI) in the presence of the glycine peptides, triglycine, tetraglycine, and pentaglycine resulted in the formation of both Cr(V)-methanol and Cr(V)-peptide intermediates, while only the Cr(V)-peptide complexes were detected in the reactions with the alanine peptides trialanine, tetraalanine, and pentaalanine. Similar EPR signals were observed for all of the Cr(V)-peptide complexes with giso values between approximately 1.986 and approximately 1.979, and AN values of (2.1-2.6) x 10(-4) cm-1. PMID- 11195394 TI - Bimetallic cyanide-bridged complexes based on the photochromic nitroprusside anion and paramagnetic metal complexes. Syntheses, structures, and physical characterization of the coordination compounds [Ni(en)2]4[Fe(CN)5NO]2[Fe(CN)6]x5H2O, [Ni(en)2][Fe(CN)5NO]x3H2O, [Mn(3 MeOsalen)(H2O)]2[Fe(CN)5NO], and [Mn(5-Brsalen)]2[Fe(CN)5NO]. AB - The synthesis, crystal structure, and physical characterization of the coordination compounds [Ni(en)2]4[Fe(CN)5NO]2[Fe(CN)6]x5H2O (1), [Ni(en)2][Fe(CN)5NO]x3H2O (2), [Mn(3-MeOsalen)(H2O)]2[Fe(CN)5NO] (3), and [Mn(5 Brsalen)]2[Fe(CN)5NO] (4) are presented. 1 crystallizes in the monoclinic space group P2(1)/n (a = 7.407(4) A, b = 28.963(6) A, c = 14.744(5) A, alpha = 90 degrees, beta = 103.26(4) degrees, gamma = 90 degrees, Z = 2). Its structure consists of branched linear chains formed by cis-[Ni(en)2]2+ cations and ferrocyanide and nitroprusside anions. The presence of two kinds of iron(II) sites has been demonstrated by Mossbauer spectroscopy. 2 crystallizes in the monoclinic space group P2(1)/c (a = 11.076(3) A, b = 10.983(2) A, c = 17.018(5) A, alpha = 90 degrees, beta = 107.25(2) degrees, gamma = 90 degrees, Z = 4). Its structure consists of zigzag chains formed by an alternated array of cis [Ni(en)2]2+ cations and nitroprusside anions. 3 crystallizes in the triclinic space group P1 (a = 8.896(5) A, b = 10.430(5) A, c = 12.699(5) A, alpha = 71.110(5) degrees, beta = 79.990(5) degrees, gamma = 89.470(5) degrees, Z = 1). Its structure comprises neutral trinuclear bimetallic complexes in which a central [Fe(CN)5NO]2- anion is linked to two [Mn(3-MeOsalen)]+ cations. 4 crystallizes in the tetragonal space group P4/ncc (a = 13.630(5) A, c = 21.420(8) A, Z = 4). Its structure shows an extended 2D neutral network formed by cyclic octameric [-Mn-NC-Fe-CN-]4 units. The magnetic properties of these compounds indicate the presence of quasi-isolated paramagnetic Ni2+ and Mn3+. Irradiated samples of the four compounds have been studied by differential scanning calorimetry to detect the existence of the long-lived metastable states of nitroprusside. PMID- 11195395 TI - [CoII(4-terpyridone)2]X2: a novel cobalt(II) spin crossover system [4-terpyridone = 2,6-bis(2-pyridyl)-4(1H)-pyridone]. PMID- 11195396 TI - A three-dimensional extended Sb network in the metallic antimonides (M',Ti)5Sb8 (M' = Zr, Hf, Nb, Mo). AB - (M',Ti)5Sb8 was prepared from the melt by arc-melting suitable mixtures of Ti, TiSb2, and M'Sb2, respectively. This phase exists at least with M' = Zr, Hf, Nb, and Mo. A significant phase range for Zr delta Ti5 - delta Sb8 was found to be within 1.10(8) < or = delta < or = 3.9(3). All (M',Ti)5Sb8 representatives investigated occur in the same, yet hitherto unknown structure type, as determined by single-crystal analyses. E.g., the lattice dimensions of Zr delta Ti5 - delta Sb8 range from a = 654.49(3) pm, c = 2662.4(2) pm for delta = 1.10(8) to a = 671.06(6), c = 2679.7(4) pm for delta = 3.9(3) (space group I4(1)22, No. 98, Z = 4). The three chemically inequivalent metal sites are statistically occupied by different mixtures of the M atoms M' and Ti, included in a three dimensional network of Sb atoms on 6- to 8-fold Sb coordinated positions. Sb-Sb bonds of intermediate lengths occur in addition to the predominating heteronuclear M-Sb bonds. Physical property measurements of (Zr,Ti)5Sb8 reveal these phases being metallic exhibiting specific resistances of several m omega.cm and a small Seebeck coefficient at room temperature, in agreement with the results of the electronic structure calculations on the LMTO and extended Huckel levels. The calculations indicate a possible change to semiconducting properties by heavy doping. PMID- 11195397 TI - [The effect of exogenous nitric oxide on endothelial dysfunction in two-kidney, one-clip renovascular hypertensive rats]. AB - Previous studies have shown that hypertension causes endothelial dysfunction. To study the influence of exogenous nitric oxide(NO) on endothelial dysfunction produced by hypertension, we administered a non-depressor dose of nipradilol to two-kidney, one-clip renovascular hypertensive rats(2K1C). Sprague-Dawley rats underwent either sham surgery(G-1) or clipping of the left renal artery. From day seven, 2K1C were randomized into 3 groups, placebo treatment(G-2), nipradilol treatment(G-3,) and propranolol treatment(G-4). Urinary NO2- + NO3-(NOx) excretion (UNOx V) was measured 4 weeks after clipping, and then, acetylcholine(Ach), A23187, or sodium nitroprusside(SNP)-induced relaxation were measured in the aorta. Blood pressure was increased in G-2, G-3, and G-4 compared to G-1. UNOx V was lower in G-2, G-3, and G-4 compared to G-1, but UNOx V was higher in G-3 compared to G-2 and G-4. Although Ach or A23187-induced relaxation was significantly decreased in isolated artery from G-2, G-3, and G-4 compared with those from G-1. Ach- or A23187-induced relaxation was improved in G-3. SNP induced relaxation did not differ among the 4 groups. These results suggest that exogenous NO from nipradilol reduces the endothelial dysfunction caused by hypertension without changing the blood pressure. PMID- 11195398 TI - [Ambulatory blood pressure monitoring in hypertensive CAPD patients]. AB - The periodic structure of 24-hour blood pressure variation(circadian rhythm of blood pressure by ambulatory blood pressure monitoring(ABPM) in hypertensive CAPD patients was investigated by a new method of analysis based upon the maximum entropy method(MEM). In addition, this method allows the adequacy of antihypertensive therapies to be evaluated in such patients. The results were as follows; 1) The frequency of non-dipper type hypertension was 88%(36/41 cases), and the remaining 12% (5/41) were dipper type hypertension patients. The rise in morning blood pressure(morning surge: MS) was noted in 64% of the former. 2) Night time systolic blood pressure(182 +/- 22 mmHg, n = 36) was higher in patients with non-dipper type hypertension than in those with the dipper type(151 +/- 17 mmHg, n = 5, p < 0.01). 3) The standardized level of systolic blood pressure(SLSBP) calculated by MEM analysis in patients with non-dipper type hypertension(177 +/- 7 mmHg) was comparable with that in those with dipper type hypertension(168 +/- 13 mmHg, ns). 4) Treatment with long-acting Ca antagonist alone significantly reduced both SLSBP and the area over the SLSBP from 188 +/- 18 mmHg to 160 +/- 7 mmHg(p < 0.01, n = 8), and area over the SLSBP from 2,735 +/ 340 mmHg.hr to 1,945 +/- 298 mmHg.hr(p < 0.01, n = 8). 5) In addition to long acting Ca antagonist, administration of alpha 1-blocker given at bed time was significantly efficacious in reducing the rise in morning blood pressure, MS. The present study using MEM analysis of ABPM suggests that the blood pressure profile of hypertensive CAPD patients is characterized by a non-dipper type dominance and a frequent morning surge. Furthermore, the combined therapy with long-acting Ca antagonist and alpha 1-blocker was substantially effective both in reducing the overall blood pressure level, and in inhibiting the MS. This combined antihypertensive therapy may be potentially useful to prevent CAPD patients from the future development of cardiovascular complications. PMID- 11195399 TI - [The effects of ACE inhibitor treatment and ACE gene polymorphism on erythropoiesis in chronic hemodialysis patients]. AB - Aggravation of anemia in chronic renal failure patients by angiotensin-converting enzyme inhibitors (ACEIs) has been attributed to the inhibition of angiotensin II which facilitates erythropoietin(Epo) production. This study was aimed at evaluating whether ACEIs aggravate anemia in maintenance hemodialysis patients and to investigate the influence of ACE gene polymorphism on erythropoiesis in these patients. Ninety-one hemodialysis patients were divided into 2 groups, based on whether or not they were administered ACEIs, into the ACEI group(n = 24) and the non-ACEI group(n = 67), and comparisons were made of the doses of recombinant human Epo(rHuEpo) administered, the hematocrit(Hct) and the plasma Epo concentrations. Among the patients in the non-ACEI group, only 17 did not receive rHuEpo, while all of the patients in the ACEI group received rHuEpo. The average dose of rHuEpo was 102.7 +/- 45.4 IU/kg/week in the ACEI group and 57.8 +/- 55 IU/kg/week in the non-ACEI group and the difference between the two groups was statistically significant. A statistically significant difference in the Hct was also observed between the two groups: the mean Hct in the ACEI group was 28.7 +/- 2.9% while that in the non-ACEI group was 31.1 +/- 3.7%. The plasma Epo concentrations were significantly lower in the ACEI group than in the non-ACEI group. No significant differences in the rHuEpo dose and Hct were observed between the three ACE genotype classes in either the ACEI or the non-ACEI group, however, there was a significant difference among the three genotypes in the non ACEI group in regard to the plasma Epo concentrations; patients with the DD genotype had higher concentrations than those with the DI or II genotypes. These data suggest that anemia in maintenance hemodialysis patients is worsened by ACEIs as a result of the suppression of Epo production. Although it has been suggested that the endogenous Epo concentrations in maintenance hemodialysis patients are associated with ACE gene polymorphism, no significant influence of the ACE genotype on the rHuEpo dose or Hct was evident. Therefore, it is possible that exacerbation of anemia by ACEIs in the patients receiving rHuEpo is a result of an inhibited bone marrow response to Epo. PMID- 11195400 TI - [A case of high-age minimal change nephrotic syndrome relapse after 18-year remission and effective treatment with steroid and cyclosporin combined therapy]. AB - We describe the clinical course of a 69-year-old woman, who suffered from minimal change nephrotic syndrome(MCNS) after long-term remission. In 1979, she was admitted to Kanazawa University Hospital due to MCNS verified by renal biopsy and was treated with oral prednisolone(initially 40 mg/day) for two years. She suffered from edema again in 1999 with massive proteinuria. Renal biopsy revealed minor glomerular abnormality without any deposition of immunoglobulins or complements. Electron microscopic findings showed extensive foot process effacement. Therefore, we diagnosed this case as a recurrence of MCNS. She was treated with the combination of methylprednisolone pulse therapy(500 mg, 3 days), oral prednisolone(20 mg/day) and cyclosporin(CyA, 3 mg/kg/day), which could induce earlier complete remission. These results suggest that recurrence after long-term remission could occur in adult-onset MCNS and that the combination therapy of prednisolone and CyA may be effective for the induction of early remission in MCNS. PMID- 11195402 TI - NCCN outcomes research database: data collection via the Internet. AB - Since 1997, the National Comprehensive Cancer Network (NCCN) outcomes database has successfully collected and reported patterns of care and outcomes data in the oncology setting. Breast cancer was the first cancer site chosen for this outcomes study, with non-Hodgkin's lymphoma targeted as the next site. Quarterly reports of the data are compiled and distributed to all participating centers. The results for each institution are given to the Principal Investigator at the respective institution. At present, the NCCN database contains more than 100,000 records of longitudinal data on more than 5,000 women with breast cancer. Extending data collection to the community setting is a goal. PMID- 11195401 TI - [Three cases of severe hyponatremia under taking selective serotonin reuptake inhibitor (SSRI)]. AB - The association between selective serotonin reuptake inhibitors(SSRIs) and hyponatremia has been documented throughout the world. In Japan, since SSRIs have recently come into use for patients with depression, there are only a few reports of hyponatremia associated with SSRIs. We present here three cases of the syndrome of inappropriate secretion of antidiuretic hormone(SIADH) associated with the administration of fluvoxamine for depression. They were admitted to our hospital because of deep coma, and revealed severe hyponatremia. Their serum sodium levels were 103-112 mEq/l, serum osmolalities were 227-241 mmol/kg, urine sodium levels were 38-107 mEq/l, and urine osmolalities were 352-781 mmol/kg. These patients were started on fluvoxamine 3 days-3 months previously. The diagnosis of SIADH in these patients was made based on hyponatremia, and low serum and high urine osmolalities. The fluvoxamine treatment was discontinued, and hypertonic saline was infused. Their serum sodium levels and osmolalities were subsequently normalized. None of the other known causes of hyponatremia, including diuretic therapy, tumors, and respiratory and central nervous system diseases, were present. High plasma AVP levels observed in the two cases suggest that SSRIs stimulate AVP secretion, thereby causing SIADH. Many reports have shown that people older than 70 years were at a particularly high risk of developing hyponatremia when SSRIs were used. In the future, since the use of SSRIs will be increasing, the water and electrolyte balance of elderly patients should be monitored carefully during SSRIs therapy. PMID- 11195403 TI - Using tumor registry resources in analyzing concordance with guidelines and outcomes. AB - Collection and analysis of standardized multi-institutional outcomes data is a labor-intensive process. As the National Comprehensive Cancer Network (NCCN) seeks to expand its Outcomes Database to include multiple primary tumor types, the amount of time and effort required for detailed data abstraction and transmission will become an obstacle for many primary institutions. In addition, as the NCCN Guidelines become more widely distributed and adopted in the oncology community, it would be appealing to evaluate guideline concordance and quality of care in community hospitals and community-based physician practices vs major cancer centers. However, methods for case finding and collection of detailed outcomes data in the community setting are not well established. Most cancer centers and community hospitals have already set aside resources for maintaining a local tumor registry that includes limited information on demographics, diagnosis, staging, treatment, and survival for all new cancer patients treated at the specific institution. One strategy that can be used to facilitate a global outcomes program within the NCCN community calls for capitalizing on existing local database resources and experienced coding and data management staff. PMID- 11195404 TI - The managed-care perspective for improving quality. AB - The role of managed-care organizations (MCOs) is to determine the existence of a benefit and how it is to be covered. Clinical guidelines and evidence-based medicine are critical parts of those decisions, and help drive much of the medical policies of MCOs. The goal is to identify and support medically appropriate and cost-effective interventions, and not cover treatments that do not have those characteristics. This will become increasingly important as more payers move to defined contribution plans, which place added responsibility for care decisions on the medical care consumer. Improving quality, creating consistency, and establishing the credibility of MCOs and their guidelines are imperative for integrating evidence-based medicine into coverage decisions. The ultimate outcome sought by MCOs and payers is improvement of the health of the populations they serve. PMID- 11195405 TI - NCCN Practice Guidelines for Prostate Cancer. AB - Systemic therapies for prostate cancer are likely to improve, and as they do, they will have enormous impact on the treatment of high-risk and locally advanced cancers. Further technical improvements in radiotherapy and alternative local modalities, such as cryoablation, are also likely, and will bring even more options for local control. It is certain these guidelines will continue to evolve. PMID- 11195406 TI - New developments in the treatment of acute myeloid leukemia. AB - Curative therapy for acute myeloid leukemia (AML) remains unsatisfactory. However, three recent advances may play an important role in determining how AML is treated in the near future. First, the development of targeted antibody therapy using the anti-CD33-calicheamicin conjugate (gemtuzumab ozogamicin, Mylotarg) represents a novel targeted approach to the killing of leukemia cells. Second, modern molecular methods have improved our ability to identify minimal residual disease (MRD) in patients who appear to be in remission. These methods will allow physicians to tailor therapy, offering, for example, more intensive therapy to patients who harbor MRD. Lastly, the development of microarray gene expression technology allows for the simultaneous study of thousands of genes. With this technology, we may determine the genes responsible for the biological properties of treatment response and relapse in leukemia patients. PMID- 11195408 TI - NCCN Practice Guidelines for Cancer-Related Fatigue. AB - These guidelines propose a treatment algorithm in which patients are evaluated regularly for fatigue, using a brief screening instrument, and are treated as indicated by their fatigue level. The algorithm's goal is to identify and treat all patients with fatigue that causes distress or interferes with daily activities or functioning. Management of fatigue begins with primary oncology team members who perform the initial screening and either provide basic education and counseling or expand the initial screening to a more focused evaluation for moderate or higher levels of fatigue. At this point the patient is assessed for the five primary factors known to be associated with fatigue: pain, emotional distress, sleep disturbance, anemia, and hypothyroidism. If any of these conditions are present, it should be treated according to practice guidelines, and the patient's fatigue should be reevaluated regularly. If none of the primary factors is present or the fatigue is unresolved, a more comprehensive assessment is indicated--with referral to other care providers as appropriate. The comprehensive assessment should include a thorough review of systems, review of medications, assessment of comorbidities, nutritional/metabolic evaluation, and assessment of activity level. Management of fatigue is cause-specific when conditions known to cause fatigue can be identified and treated. When specific causes, such as infection, fluid and electrolyte imbalances, or cardiac dysfunction, cannot be identified and corrected, nonpharmacologic and pharmacologic treatment of the fatigue should be considered. Nonpharmacologic interventions may include a moderate exercise program to improve functional capacity and activity tolerance, restorative therapies to decrease cognitive alterations and improve mood state, and nutritional and sleep interventions for patients with disturbances in eating or sleeping. Pharmacologic therapy may include drugs such as antidepressants for depression or erythropoietin for anemia. A few clinical reports of the use of corticosteroids and psychostimulants suggest the need for further research on these agents as a potential treatment modalities in managing fatigue. Basic to these interventions, the effective management of cancer-related fatigue involves an informed and supportive oncology care team that assesses patients' fatigue levels regularly and systematically and incorporates education and counseling regarding strategies for coping with fatigue (Johnson, 1999), as well as using institutional fatigue management experts for referral of patients with unresolved fatigue. PMID- 11195407 TI - NCCN Practice Guidelines for Cancer Pain. AB - The overall approach to pain management encompassed in these guidelines is comprehensive. It is based on objective pain assessments, utilizes both pharmacologic and nonpharmacologic interventions, and requires continual reevaluation of the patient. The NCCN Cancer Pain Practice Guidelines Panel believes that cancer pain can be well controlled in the vast majority of patients if the algorithms presented are systematically applied, carefully monitored, and tailored to the needs of the individual patient. PMID- 11195409 TI - NCCN Practice Guidelines for Head and Neck Cancers. PMID- 11195410 TI - Oncology business update. AB - This article explores a variety of environmental factors that influence the delivery of oncology care in both academic and community settings. These factors include fragmentation of the managed-care process, increased backlash to managed care organizations, greater federal and state intervention, and new technologies, medicines, and procedures. The author also discusses continued consolidation of managed-care organizations, as well as how physicians and hospitals are being compensated for oncology services. Other topics explored include the progress of case rate and capitation as an alternative to fee-for-service medicine, the latest events in insurer coverage of clinical trials, and the progress of oncology disease management. In addition, the author discusses the interest of national payers in the management of oncology services and delivery mechanisms for highly specialized oncology services. PMID- 11195411 TI - NCCN Practice Guidelines for Colorectal Cancer. AB - The NCCN Colorectal Cancer Guidelines panel believes that a multidisciplinary approach is necessary for the management of the patient with colorectal cancer. The panel endorses the concept that treatment of patients in a clinical trial has priority over standard or accepted therapy. The recommended surgical procedure for resectable colon cancer is an en bloc resection; laparoscopic surgery should be done only in the context of a clinical trial. For patients with stage III disease, 5-FU-based adjuvant therapy is recommended. A patient who has metastatic disease in the liver or lung should be considered for surgical resection if he or she is a candidate for surgery and if surgery can extend survival. Surgery should be followed by adjuvant chemotherapy. The panel advocates a conservative post treatment surveillance program for colon and rectal carcinoma patients. Serial CEA determinations are appropriate if the patient is a candidate for aggressive surgical resection, should recurrence be detected. Abdominal and pelvic CT scans should be utilized only when there are clinical indications of possible recurrence. Patients whose disease progresses during 5-FU-based therapy should be treated with irinotecan or encouraged to participate in a phase I or phase II clinical trial. PMID- 11195412 TI - The NCCN/American Cancer Society partnership. AB - The National Comprehensive Cancer Network (NCCN) partnered with the American Cancer Society two years ago in an effort to translate the NCCN Practice Guidelines for professionals into guidelines for patients. The response from patients to the first two guidelines was overwhelmingly positive. The following panel discussion provides some background information on this alliance and discusses the development and highlights of their latest collaboration, the Colorectal Cancer Patient Guidelines. PMID- 11195413 TI - Novel therapeutic approaches for metastatic colorectal cancer. AB - More than 4 decades after its discovery, 5-FU remains an important part of the treatment of colorectal cancer. However, the advent of new agents and the discovery of novel molecular targets have opened a new era in the treatment of this disease. Recent trials of combinations of 5-FU, leucovorin, and either irinotecan or oxaliplatin have produced exciting results that warrant consideration of these regimens as front-line therapies for colorectal cancer. Having produced consistent improvements in response rate, progression-free survival duration, and overall survival duration, the combination of 5-FU, leucovorin, and irinotecan is rapidly becoming the standard against which newer regimens will be compared. Nevertheless, the improvements in survival achieved so far have remained relatively small. Whenever possible, patients should be encouraged to participate in well-designed clinical trials of new regimens. Despite the impressive advances of the past few years, advanced colorectal cancer remains a highly lethal disease. PMID- 11195414 TI - General guidelines for the management of older patients with cancer. AB - Because aging is highly individualized, the best guide to treatment of the older patient with cancer may be provided by a comprehensive assessment that evaluates such diverse areas as functional status, comorbidity, socioeconomic conditions, nutrition, polypharmacy, and the presence or absence of geriatric syndromes. Aging is further associated with important pharmacologic changes that involve pharmacokinetics, pharmacodynamics, and the toxicity profile of the drugs. These changes increase the risk of therapeutic complications partly because of the different behavior of the disease in an older patient population and partly because of a decreased tolerance to treatment in some older patients. PMID- 11195415 TI - NCCN Practice Guidelines for Chronic Myelogenous Leukemia. PMID- 11195416 TI - Role of oral chemotherapy in colorectal cancer. AB - Despite the long clinical history of 5-FU in gastrointestinal cancer, the development of oral agents has been a productive endeavor, and oral fluoropyrimidine agents are likely to play an important role in the management of colorectal cancer. Results of recent trials in advanced/metastatic colorectal cancer have shown equivalence of response rates, time to disease progression, and median survival and reduced rates of neutropenia and stomatitis with oral capecitabine (Xeloda) or UFT/leucovorin compared with standard fluorouracil (5 FU)/leucovorin regimens. Evaluation of these oral agents in adjuvant therapy, in combination chemotherapy, and in combination with radiation therapy is ongoing. PMID- 11195417 TI - The NCCN guidelines development process and infrastructure. AB - A major task of the National Comprehensive Cancer Network (NCCN) is to develop pathways reflecting the major step-by-step management decisions required to provide care for patients with cancer. The determination of what is appropriate care involves assessing the balance between the sum of the benefits compared to the sum of the risks. The guidelines are composed of recommendations based on the best evidence available at the time they are derived. Each guideline is reviewed annually and once revisions have been uniformly accepted, the new version becomes the official NCCN guideline for that year. PMID- 11195418 TI - NCCN Practice Guidelines for Breast Cancer. AB - The therapeutic options for patients with noninvasive or invasive breast cancer are complex and varied. In many situations, the patient and physician have the responsibility to jointly explore and ultimately select the most appropriate option from among the available alternatives. With rare exception, the evaluation, treatment, and follow-up recommendations contained within these guidelines were based largely on the results of past and present clinical trials. However, there is not a single clinical situation in which the treatment of breast cancer has been optimized with respect to either maximizing cure or minimizing toxicity and disfigurement. Therefore, patient and physician participation in prospective clinical trials allows patients not only to receive state-of-the-art cancer treatment but also to contribute to the improvement of treatment of future patients. PMID- 11195419 TI - NCCN Practice Guidelines for Acute Myelogenous Leukemia. PMID- 11195420 TI - Oncology legislative update. AB - This article reviews current legislative and regulatory issues of importance to the oncology community. Topics include patient protection, Medicare support of clinical trials, research data protection, the Medical Innovation Tax Credit, National Cancer Institute appropriations, and medical record privacy issues. Other topics discussed included funding for stem-cell research, genetic therapy oversight, and coverage for uninsured patients. PMID- 11195421 TI - Contribution of anemia to fatigue in the cancer patient. AB - One of the goals of the proposed National Comprehensive Cancer Network Practice Guidelines for Cancer-Related Fatigue is outlining a systematic approach to the evaluation, intervention, and assessment of outcome in the treatment of fatigue. Anemia has been characterized as a major contributor to fatigue, and a review of patients receiving cancer therapy showed that the majority developed anemia. The current data support the value of returning hemoglobin levels to the normal range in terms of maximizing improvements in quality of life related to anemia. The potential impact of anemia in terms of treatment outcome is under investigation. PMID- 11195422 TI - Considerations in the management of myeloma. AB - Multiple myeloma remains an incurable cancer. In recent years, progress in different drug classes has improved outcomes, but management has become more complicated. Areas such as prognostic classification, the increased use of high dose chemotherapy with autologous stem-cell rescue, and a wider array of ancillary drugs must be integrated into recommendations for a consolidated treatment plan. Estimating prognosis is dependent on both clinical features and a growing list of laboratory tests. Autologous transplantation has been applied to an increasing proportion of patients, at different points in the disease process. Besides the age cut-off issue, there are still significant treatment choices to be made within the transplant technique. Newer drugs, most recently, thalidomide (Thalomid), may offer benefits independent of conventional cytotoxic drugs or steroids. Use of ancillary drugs, such as bisphosphonates, interferon, P glycoprotein blockers, antibiotics, and growth factors, are also discussed. For the future, immunotherapy in the posttransplant setting appears promising. Ultimately, basic research must identify intracellular targets for the development of specific new-generation drugs. PMID- 11195423 TI - Managed care companies and the practice of medicine. AB - One of the major issues pertaining to the pending legislation for Patient's Bill of Rights is the potential of liability health care plans, particularly when they decline coverage they consider not medically necessary. We call these contracts "managed health care" plans. But, realistically, when is it managing? When is it medicine? When, if at all, does management undermine medicine? And if it does, should managed care organizations--and their representatives--be held legally liable for medical decisions that go wrong? A panel of seven experts examines these questions from medical, payment, patient, legal, insurance, and governing viewpoints. PMID- 11195424 TI - National Cancer Policy Board Report. AB - While collecting information for a consumer pamphlet to assist cancer patients in navigating through the medical system, the National Cancer Policy Board discovered the data that were available were critically insufficient. In response, the turned their attention to analyzing our ability to assess quality of cancer care. Their findings along with ten recommendations were published in April 1999. In particular, their conclusions concerning data collection and volume outcomes surprised many in the oncology community. These comments along with five of their recommendations--high-volume settings, standard guidelines, the elements of quality care, measuring and monitoring quality care, and end-of life care--are presented in this panel discussion. PMID- 11195425 TI - Influence of benzyl benzoate as oil core on the physicochemical properties of spray-dried powders from polymeric nanocapsules containing indomethacin. AB - To prepare spray-dried powders of poly(D,L-lactic acid) (PLA) or poly-epsilon caprolactone (P epsilonC) from colloidal suspensions containing indomethacin (IND) using benzyl benzoate (BnB), nanocapsules (NC) were prepared by nanoprecipitation. To select the best NC formulations, increasing drug concentrations were tested (1.0, 1.5, or 2.0 mg/mL). The particle size was measured by Nanosizer. Spray-dried powders (SDP) were prepared by addition of Aerosil 200 into suspensions of NC. IND was assayed by HPLC. Free IND was determined using an Ultrafree. NC-SPD were examined under SEM. The particle sizes of all formulations are in the sub-300 nm range and are IND-associated, with drug recovery close to 100%. After 1 month, the formulations with highest drug content (2.0 mg/mL) showed a decline of total quantity of IND. After spray-drying, IND recovery for SDP presented values above 100%, indicating that the drug was concentrated from loss of mass during the process. To verify the relationship of oil phase with this loss of mass, similar NC (IND 1.5 mg/mL) prepared with Miglyol 810 (MI) were spray-dried, and SEM analysis showed nanostructures adsorbed onto SiO2. Similar nano-structures were not visualized for NC samples prepared with BnB. A swelling experiment showed the complete dissolution of both polymer by the BnB, whereas for MI the polymer masses remained unchanged. In conclusion, BnB is a solvent for PLA and P epsilonC and this ester is entrained during spray-drying. Despite the use of BnB in formulations of NC, PLA, or P epsilonC, colloidal suspensions prepared with BnB could be micelles instead of nanocapsules. PMID- 11195426 TI - Pluronic F127-based ocular delivery system containing biodegradable polyisobutylcyanoacrylate nanocapsules of pilocarpine. AB - The objectives of our study were to prepare a biodegradable polyisobutylcyanoacrylate (PIBCA) colloidal particulate system of pilocarpine, to incorporate it into a Pluronic F127(PF127)-based gel delivery system, and to evaluate its ability to prolong the release of pilocarpine. Polyisobutylcyanoacrylate nanocapsules (PIBCA-NC) of pilocarpine were prepared by interfacial polymerization. Physicochemical characterization of the colloidal dispersion of PIBCA-NC of pilocarpine was performed by measuring drug loading, particle size analysis, and scanning electron microscopy. Results indicated that approximately 13.5% of pilocarpine was loaded onto the PIBCA-NC, the nanocapsules ranged from 370 to 460 nm, the distribution was narrow, and there was no significant effect of stirring speed on particle size. The PIBCA-NC dispersion of 1% pilocarpine alone (I) and after incorporation into the Pluronic F127 gel delivery system (II) were compared against 1% pilocarpine incorporated into a PF127 gel containing 5% methylcellulose (PF127MC) alone (III) by measuring the miotic response in the albino rabbit eye. Statistical analysis indicated a rank order for both the duration and intensity of miosis of II > III >> I, with all differences being significant (p < 0.05). Thus, it appears that II increases the contact time of pilocarpine with the absorbing tissue in the eye, thereby improving ocular bioavailability. The PIBCA-NC of pilocarpine dispersed in the PF127MC gel delivery system has considerable potential for achieving a prolonged delivery for such drugs as pilocarpine and other more hydrophobic drugs. PMID- 11195427 TI - Targeting of liposomal andrographolide to L. donovani-infected macrophages in vivo. AB - Despite the rapid development in medicinal and pharmaceutical technology, the targeting of drugs to phagocytic cells in macrophage-related diseases still remains a major unsolved problem. By using the mannosyl-fucosyl receptors on macrophages, attempts were made to target antileishmanial drugs encapsulated in mannosylated or fucosylated liposomes to treat experimental leishmaniasis in the hamster model. Mannosylated liposomes were found to be more potent in delivering antileishmanial drugs to phagocytic cells. Liposomes loaded with an indigenous drug, andrographolide, a labdane diterpenoid isolated from Indian medicinal plant Andrographis paniculata, were prepared and tested against experimental leishmaniasis in a hamster model. Mannosylated liposomes loaded with the drug were found to be most potent in reducing the parasitic burden in the spleen as well as in reducing the hepatic and renal toxicity. In addition, mannosylated drug-loaded liposome-treated animals showed a normal blood picture and splenic tissue histoarchitecture when compared with those treated with free drug or regular liposomal drug. Such a drug-vehicle formulation may be considered for clinical trials. PMID- 11195428 TI - Effect of nanoparticles on digitoxin uptake and pharmacologic activity in rat glomerular mesangial cell cultures. AB - Our experiments analyzed the uptake of free and nanoparticles (NP)-associated digitoxin (DGT) by rat glomerular mesangial cells. NP were prepared by the nanoprecipitation method using the biodegradable polyester, polycaprolactone (PCL). Prior to in vitro experiments, the systems were characterized by means of spectrofluorimetry, dynamic light scattering, and size exclusion chromatography (SEC). The loading efficiency was 80.30 +/- 1.03% of the initial DGT amount in the preparation, and the average particle size was 176 +/- 8 and 161 +/- 6 nm for DGT-NP and "empty" NP, respectively. SEC studies revealed noncovalent interactions among the different chemical compounds in the formulation. In vitro experiments were conducted at 37 degrees C and pH 7.5 by incubating "empty" NP, free DGT or DGT-NP (10 microg PCL/mL; 100 ng DGT/mL) with glomerular mesangial cells for 30 and 60 min. Uptake of DGT by the cells was favored by its incorporation into PCL-NP and showed time dependency. After 30 min of incubation, no significant differences of drug uptake were seen between free DGT (13.1 +/- 2.8%) or DGT-NP (17.4 +/- 4.9%); however, the uptake of DGT, when it was associated to the polymeric carrier, increased by approximately 2-fold (37.8 +/- 5.7%) at 60 min, whereas no significant changes were observed for free drug (20.0 +/- 6.8%). The pharmacologic activity of the drug was evaluated by measuring the planar cell surface area (PCSA). "Empty" NP, free drug, or DGT-NP did not produce significant variations on the PCSA as compared with control cells after a 30-min incubation. Nonetheless, DGT-NP reduced the PCSA to 82.51 +/- 8.42% of control values when the incubation lasted 60 min. The ability of cells to exclude the trypan blue dye and the leakage of lactate dehydrogenase into the medium revealed no signs of increased toxicity from incorporation of DGT into PCL-NP. Therefore, PCL-NP improved drug uptake by the cells without altering the pharmacologic activity and toxicity of the drug. Thus, they can be a useful approach to target drugs to the kidneys or the heart. PMID- 11195429 TI - Development and evaluation of nasal formulations of ketorolac. AB - Ketorolac tromethamine is a potent non-narcotic analgesic with moderate anti inflammatory activity. Clinical studies indicate that ketorolac has a single dose efficacy greater than morphine for postoperative pain and has excellent applicability in the emergency treatment of pain. Due to incomplete oral absorption of ketorolac, several approaches have been tried to develop a nonoral formulation in addition to injections, especially for the treatment of migraine headache. The aim of our study was to develop a nasal formulation of ketorolac with a dose equivalent to the oral formulation. A series of spray and lyophilized powder formulations of ketorolac were administered into the nasal cavity of rabbits, and their pharmacokinetics profiles were assessed. The spray and powder formulations were compared through their pharmacokinetics parameters and absolute bioavailability. Drug plasma concentration was determined using solid phase extraction, followed by an HPLC analysis. Nasal spray formulations were significantly better absorbed than powder formulations. A nasal spray formulation of ketorolac tromethamine showed the highest absorption with an absolute bioavailability of 91%. Within 30 min of administration, the plasma concentration was comparable to that resulting from an intravenous injection. The absolute bioavailability of a solution of ketorolac acid was 70%. Apparently, the dissolution of ketorolac acid into the mucous layer limits its absorption. There were no significant differences in absorption between different powder formulations. Even the reduction of particle size from 123 microm to 63 microm did not indicate better absorption of ketorolac tromethamine from powder formulations. Interestingly, the absolute bioavailability of ketorolac tromethamine from a powder formulation is only 38%, indicating that the drug may not be totally released from the polymer matrix before it is removed from nasal epithelium by mucociliary clearance. PMID- 11195430 TI - Effect of nicotinic acid conjugated to DNA-transfecting complexes targeted at the transferrin receptor of HeLa cells. AB - A conjugate consisting of streptavidin (biotinylated transferrin)-biotinylated polylysine for DNA delivery to cells was modified by partial nicotinylation of the polylysine component of the conjugate and used for transfection studies. A conjugate of biotin10-nicotinyl60-polylysine250 containing 60 weakly basic nicotinyl (pyridine-3-carboxyl) residues was prepared. The design of the modified polylysine was directed to the possible binding of H+ ions in the endosome lysosomal vesicles (pH 5-6) by the nicotinyl groups, thus circumventing the use of chloroquine. The results obtained, however, while showing a 5- to 6-fold increase in luciferase transfection activity still necessitated an absolute requirement for chloroquine. A further polylysine conjugate containing a larger number of nicotinyl residues, biotin10-nicotinyl120-polylysine250, also was prepared and studied. This macromolecule stimulated luciferase activity to a small extent and was also dependent on chloroquine. Smaller biotinylated polylysine100 conjugates containing nicotinyl groups were also prepared. These were biotin10-nicotinyl30-polylysine100, and biotin10-nicotinyl60-polylysine100, respectively. Both substances, however, gave opaque, hazy aqueous solutions with precipitates on standing and could not be used for further experimental work. The results indicate that the introduction of weakly basic nicotinyl (pyridine-3 carboxyl) groups onto polylysine250 give conjugates that are unable to replace the lysosomotrophic agent chloroquine in the HeLa cell sysem studied. A 5- to 6 fold increase in luciferase activity, however, was found with biotin10 nicotinyl60-polylysine250. PMID- 11195431 TI - Positively charged gelatin microspheres as gastric mucoadhesive drug delivery system for eradication of H. pylori. AB - Gastric mucoadhesive drug delivery systems are very promising for eradication of Helicobacter pylori (H. pylori), a spiral bacterium that resides in the gastric mucus layer and at the mucus-epithelial cell interface. New positively charged biodegradable microspheres were prepared using aminated gelatin by surfactant free emulsification in olive oil, followed by a cross-linking reaction with glutaraldehyde. The amino group contents of the modified gelatin and the microspheres were determined using a 2,4,6-trinitrobenzenesulfonic acid method. With the increase of glutaraldehyde concentration, the amino group content of the microspheres decreased accordingly. The influence of glutaraldehyde concentration, cross-linking reaction time, drug-loading patterns, and type of release media on the in vitro release characteristics of amoxicillin from the microspheres was investigated. Amoxicillin release rate from the modified gelatin microspheres was significantly reduced compared with that from gelatin microspheres. Furthermore, the release was decreased with the increase of glutaraldehyde concentration and/or cross-linking time. On the other hand, a faster release was observed in a lower pH release medium and/or using a lower pH solution for amoxicillin loading. The gastric mucoadhesive properties of the microspheres were evaluated using RITC-labeled microspheres in an isolated rat stomach. The gastric mucoadhesion of the modified gelatin microspheres was markedly improved compared with that of gelatin microspheres. The modified gelatin microsphere proves to be a possible candidate delivery system for the effective eradication of H. pylori. PMID- 11195432 TI - Repeat efforts pay off for cardiovascular initiative. PMID- 11195433 TI - Hospital finds nutrition care pays off on all counts, cutting costs, complications, mortality. AB - Identifying and treating malnutrition early reduces hospital stays, complications, and mortality. St. Francis Healthcare Services in Wilmington, DE, reports a two-year cost avoidance of $2.4 million from the reduced length of stay attributed to its malnutrition program. The program includes a screen to identify patients at high-risk of developing malnutrition and an algorithm for aggressive restorative care. PMID- 11195435 TI - Late-night, on-site radiologist reduces X-ray errors in the ER. AB - Hospital supports after-hours' radiologist with competitors' business. St. Elizabeth Health Partners in Covington, KY, pools readings from four other facilities to provide enough work to lure radiologists into evening shifts. With radiologists now reading X-rays on-site in the ER at night, return visits due to misinterpreted exams have been almost eliminated. PMID- 11195434 TI - Sending PharmD candidates to patients' homes can avert potential medication problems. AB - Pharmacists' home visits avert outpatient medication troubles. Crozer-Keystone Health System in Springfield, PA, has pharmacy students evaluate patients at home to address risk factors that could send the patients back to the hospital. The 3 year-old program has prevented at least five hospitalizations. PMID- 11195436 TI - Pharmacy expenses generally less than $10 million in 1998. AB - Data Benchmarks: According to the American Society of Health-System Pharmacists' 1999 survey, 57% of hospital pharmacies had operating expenses of $1 million to $9 million in fiscal 1998, with hospitals in the Northeast and West leading the pack. PMID- 11195437 TI - [Rh-prophylaxis or not? Recommendations are wanted]. PMID- 11195438 TI - [Alarming increase of esophageal cancer. Is antireflux surgery an efficient prevention?]. PMID- 11195439 TI - [Rh-prophylaxis or not? Obstetric departments should make decisions if there are medical reasons which justify the treatment]. AB - In order to find out whether or not the incidence rate of RhD-immunization has increased in pregnant women who were not given antenatal prophylaxis a survey was carried out comprising 620 women. It was evident that the number of new immunizations had decreased, both in absolute numbers and in relation to the number of births during the years 1991-1998. Hence prophylactic anti-D seems not to be indicated, neither for this group of women nor for women who have had a spontaneous abortion. PMID- 11195440 TI - [Fireworks explosion in Enschede in May 2000. The course, rescue work and consequences]. PMID- 11195441 TI - [To be mentally disabled is popular in California--consequences of the new Three strikes and you're out law]. PMID- 11195442 TI - [The "filling-in-trap". Our sences deceive us]. AB - We use various strategies in order to attain a complete knowledge of reality. One of these is using "filling-in". What is and is not filling-in is discussed. The brain may process light which reaches the retina in two fundamentally different ways. The conclusion is that many a patient with perimetrically verifiable visual field defects with each eye separately experiences a complete image of his total surrounding. The quality of this image correlates to the neuronal capacity of the retina in question. What generally has been assumed to be due to filling-in is in this specific instance a newly discovered faculty in the system consisting of eye and brain naively, we have walked straight into the trap of blaming this faculty on filling-in. PMID- 11195443 TI - [Did Saint Birgitta suffer from epilepsy?]. PMID- 11195444 TI - [Scrutiny of alternative medicine. "Distant healing"--a special kind of telemedicine]. PMID- 11195445 TI - [The neglected inside of human beings. Lack of competence among personnel when it comes to patients' needs of existential and spiritual talks]. PMID- 11195446 TI - [The Santa lives dangerously]. PMID- 11195447 TI - [Cosmas and Damianos. Altruistic twin physicians who were used by rich ruling dynasty]. PMID- 11195448 TI - [Psychiatric clinics--closed or moved? Significant part of current around-the clock care is now invisible]. PMID- 11195449 TI - [Physicians--future leaders?]. PMID- 11195450 TI - [Sjonell and Stahle give misleading information on mammography screening]. PMID- 11195451 TI - [Reply: the factual matter is the most important]. PMID- 11195452 TI - [Is work-related stress the primary cause of sudden death?]. PMID- 11195453 TI - [Is it always a matter of fact to prevent HIV transmission to the fetus/child?]. PMID- 11195454 TI - [An important contribution on increased mortality among anesthesiologists should initiate a debate]. PMID- 11195455 TI - [Evidence-based discussion on therapeutic strategies for dyspepsia is valuable]. PMID- 11195456 TI - Transgenic mouse models for lung cancer. AB - Transgenic technology allows the ability to target regulatory genes to the lungs in a cell-specific fashion. Using this technology, we have generated a model to investigate the phenotypic consequences of targeting oncogenes to particular cell types in the lungs and are developing a second model for the regulated expression of oncogenes in the lung. The transgenic model involves the constitutive expression of simian virus 40 large T antigen in the Clara cells of mouse lungs. This model has been used to investigate changes in expression of cell cycle regulatory genes in the Clara cells during the transformation process, as well as the expression of the transcription factors regulating the expression of Clara cell differentiation markers. The second model we are developing investigates the regulated expression of the genes in the lungs. This system is based on the establishment of two types of transgenic lines. The regulator line consists of a chimeric transcriptional factor placed under the control of a lung-specific SPC (surfactant protein C) promoter. This chimeric regulator is composed of a transcription activation domain, the GAL4 DNA-binding domain, and a truncated progesterone receptor that is responsive to RU 486, but not to endogenous progesterone. The second transgenic mouse line contains the silent target transgene under the control of a minimal promoter with upstream activating sequences (UAS) that are recognized by the regulator transgene. Upon breeding these two lines, the resulting bitransgenic mice can then be induced to express the target transgene only with the administration of RU 486. Two generations of regulators have been evaluated on their ability to regulate the expression of a growth hormone reporter gene. This system demonstrated the inducible expression of the reporter genes in the distal airways of the lungs. PMID- 11195457 TI - Use of p53 transgenic mice in the development of cancer models for multiple purposes. AB - The tumor suppressor gene p53 is perhaps the most commonly mutated gene in human cancer, being mutated in a high percentage of colon, breast, skin, bladder, and many cancers of the aerodigestive tract. Individuals with Li-Fraumeni syndrome, who routinely have a germline mutation in the p53 tumor suppressor gene, are at high risk for lung cancer, confirming its intimate role in lung tumorigenesis in humans. In contrast, the majority of chemically induced or spontaneous cancers in rodents do not contain mutations in p53. Therefore, we examined a transgenic mouse that contains a dominant negative mutation (Arg135Val) in the p53 gene placed under the control of its own endogenous promoter. The resulting mice have 3 copies of the mutated transgene as well as 2 normal p53 alleles. In the chemical carcinogenesis studies, we employed mice containing the mutated p53 gene to examine for carcinogen susceptibility. We found that mice with the p53 mutation, on an A/J F1 background, were more susceptible to a number of potential lung carcinogens, including N-methyl-N-nitrosourea (MNU) and the known tobacco carcinogens 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo(a)pyrene (BP). Mice with a mutant p53 developed larger tumors and roughly 3 times as many tumors, emphasizing the potential effects of a p53 mutation both on tumor initiation and progression. In addition, we examined 2 nonlung carcinogens, 1,2-dimethylhydrazine (DMH), a colon carcinogen, and N-butyl-N-(4-hydroxybutyl) nitrosamine (OHBBN), a bladder carcinogen. Interestingly a germline p53 mutation increased the incidence of DMH-induced colon, lung, hepatic, and uterine tumors, while having limited effects on OHBBN-induced bladder tumors. Because of its heightened susceptibility we are examining the use of this model in smoke-induced tumorigenesis in A/J mice as well. Employing the lung adenomas induced by NNK, we found that mice with or without a p53 mutation were equally susceptible to the chemopreventive effects of dexamethasone plus myo-inisitol and green tea. These tumors, which arise in a highly reproducible manner in p53 transgenic mice following carcinogen treatment, have mutations in both p53 and the K-ras oncogene. Thus, this model appears useful for examining for potential chemotherapeutic agents. p53-mutated or wild-type mice were equally susceptible to the therapeutic effects of Taxol or Adriamycin. Interestingly, piroxicam was similarly effective in inhibiting colon tumor formation by DMH in mice with or without a mutation in the p53 tumor suppressor gene. In contrast, lung and uterine tumors developing in these mice were not susceptible to the chemopreventive effects of piroxicam. In summary, mice with mutations in the p53 tumor suppressor gene appear to be particularly applicable for basic mechanistic studies, for screening for potential carcinogens, and for screening for chemopreventive or chemotherapeutic agents. PMID- 11195458 TI - Morphometric analysis of CC10-hASH1 transgenic mouse lung: a model for bronchiolization of alveoli and neuroendocrine carcinoma. AB - Constitutive expression of human achaete-scute homolog-1 (hASH1) alone or in combination with Simian virus 40 (SV40) large T antigen (TAg) under the Clara cell 10-kDa secretory protein (CC10) promoter results in bronchiolization of alveoli and enhanced tumorigenesis, respectively. A novel morphometric system composed of series of fixed distance concentric rings originating at the bronchioloalveolar junction was used to determine spatial growth patterns. hASH1 mice exhibited progressive airway epithelial hyperplasia near this junction, and minimal changes further away in the alveolar compartment. TAg animals shared this increase, but exhibited variable distance-dependent growth. By 2 months TAg/hASH1 animals showed highly increased growth at all points measured. Remarkably, TAg/hASH1 animals expressed both CC10 and extensive neuroendocrine differentiation in airways and tumors. The results suggest that these transgenic mice provide a useful model with many similarities to human lung carcinogenesis, which originates in airway epithelium, and often reveals neuroendocrine differentiation. PMID- 11195459 TI - Polygenic resistance to mouse pulmonary adenomas. AB - Susceptibility to urethan-induced pulmonary adenomas (PA) in mice is under polygenic control. To analyze these traits in detail, we generated a set of recombinant inbred (RI) mouse strains, called SMXA, from an intercross between PA susceptible A/J and resistant SM/J, and established a strain distribution pattern (SDP) table of 158 marker loci for SMXA RI strains. From the SDP table, it was possible to estimate the allele for 4 known PA susceptibility (Pas) loci in all members of SMXA RI strains. We compared combinations of Pas loci alleles with the data of number of PA induced by urethan. One of the RI strains, SMXA24, showed extremely low PA numbers, whereas they had the A/J-derived alleles at all 4 Pas loci. F1 hybrids of SMXA24 and A/J developed as few PA as SMXA24 on exposure to urethan. To confirm the hypothesis that SMXA24 has dominant PA resistance gene(s), we examined a backcross generation to A/J for multiplicity of PA. A preliminary genome scan followed by quantitative trait locus analysis revealed two resistance loci, one on mouse chromosome 11 (MMU11) (logarithm of odds [LOD] score 4.35) and another on MMU12 (LOD score 6.47). They were named Par1 and Par3, respectively. Both loci were epistatic to Pas1, the major susceptibility loci on MMU6. We next asked if such dominant resistance loci play some role in human lung cancer by studying possible loss of heterozygosity (LOH) at syntenic chromosomal segments in 79 human lung cancers, including 30 adenocarcinomas, 25 squamous cell carcinomas (SQ), and 24 small cell carcinomas (SCC). The map positions of Par1 and Par3 correspond to human 17q11-23 and 14q11-24. Of 30 adenocarcinomas, LOH was found in 53% at 17q and in 30% at 14q. For both SQ and SCC, LOH in 17q were about 10%, but LOH in 14q was about 30% to 42%. Therefore, a gene in 17q seemed to be selective for adenocarcinomas, probably at the level of the target cell. In contrast, another gene in 14q affected all 3 types of lung carcinomas, suggesting it is related to the progression of lung tumors in general. A comparative approach may provide useful information for understanding human cancers. PMID- 11195460 TI - Fine mapping and characterization of candidate lung tumor resistance genes for the Par2 locus on mouse chromosome 18. AB - In a number of recent studies, a lung tumor resistance locus designated either Par2 or Pas7 was mapped to distal chromosome 18 in crosses between susceptible A/J and more resistant BALB/c mice. This locus is important in that it accounts for as much as 60% of the difference in lung tumor susceptibility between the A/J and BALB/c mice, both of which contain the susceptible allele of Kras2, a marker and strong candidate for the major lung tumor susceptibility gene on mouse chromosome 6. We have now fine-mapped the Par2 locus by using congenic mice that were constructed by placing part of chromosome 18 from the susceptible A/J onto the genetic background of lung tumor-resistant BALB/c mice. After 7 generations of backcrossing, N7 mice that carried 28 cM of the A/J quantitative trait locus (QTL) region were crossed to the BALB/c to generate the N8 generation. Congenic strains (N8) that contain various QTL regions were generated. N9 mice, generated from N8 males x 3 BALB/c females, were genotyped in the region of the Par2 locus and treated with an initiating dose of urethane and allowed to form lung tumors over 6 months. The mice were killed and the lung tumors counted. With this cross the Par2 locus was narrowed to a 6-cM region. Potential candidate genes in this region include Smad4, Smad2, and Dcc. Previously, we excluded Smad4 and Smad2 as candidates for Par2 based on the lack of functional polymorphism(s) and differential expression in lungs from A/J and BALB/c mice. In this study, no polymorphism of the coding sequence of Dcc was observed between A/J and BALB/c mice. Further fine mapping and positional cloning are required for the identification of the Par2 gene. PMID- 11195461 TI - Fine mapping of quantitative trait loci using advanced intercross lines of mice and positional cloning of the corresponding genes. AB - High-resolution mapping of quantitative trait loci (QTLs) is an essential step towards positional cloning and identification of the corresponding genes. Most QTL detection and mapping studies in mice have been carried out using F2 intercross and backcross populations. As a consequence of the limited number of recombination events in small chromosomal regions, this has generally permitted mapping to only relatively large confidence intervals of 20 to 40 cM. A number of population designs have been proposed to increase recombination level in crosses. This includes advanced intercross lines (AIL) described by Darvasi and Soller [Genomics. 1995; 141: 1199-1207]. In this report demonstration of the utility of the AIL approach for fine mapping of QTL, which previously had been mapped with 95% confidence interval to 20 to 40 cM in a F2 intercross, will be presented. The methodological approaches to go from the fine-mapped QTL to the identification of the actual genes and mutations are discussed. PMID- 11195462 TI - Detection of genetic alterations in mouse lung adenocarcinomas by two-dimensional gel electrophoresis. AB - DNA from 14 mouse lung adenocarcinomas and 7 normal lungs were examined by 2 dimensional gel electrophoresis (2-DGE) for genetic alterations. 2-DGE profiles from tumor samples were compared with those profiles from normal lung tissues through a computer-assisted color overlay system. Compared to the profiles in normal lung DNA, 6 spots were amplified and 16 spots were partially reduced in their intensity in tumors. Two spots were detectable only in tumor tissues. These altered spots indicate genetic changes in mouse lung tumor development. The identification of these genetic alterations is probably important in understanding mouse lung carcinogenesis. PMID- 11195463 TI - K-ras p21 expression and activity in lung and lung tumors. AB - Although K-ras is mutated in many human and mouse lung adenocarcinomas, the function of K-ras p21 in lung is not known. We sought evidence for the prevalent hypothesis that K-ras p21 activates raf, which in turn passes the signal through the extracellular signal regulated kinases (Erks) to stimulate cell division, and that this pathway is upregulated when K-ras is mutated. Results from both mouse lung tumors and immortalized cultured E10 and C10 lung type II cells failed to substantiate this hypothesis. Lung tumors did not have more total K-ras p21 or K ras p21 GTP than normal lung tissue, nor were high levels of these proteins found in tumors with mutant K-ras. Activated K-ras p21-GTP levels did not correlate with proliferating cell nuclear antigen. Special features of tumors with mutant K ras included small size of carcinomas compared with carcinomas lacking this mutation, and correlation of proliferating cell nuclear antigen with raf-1. In nontransformed type II cells in culture, both total and activated K-ras p21 increased markedly at confluence but not after serum stimulation, whereas both Erk1/2 and the protein kinase Akt were rapidly activated by the serum treatment. Reverse transcriptase-polymerase chain reaction (RT-PCR) assays of K-ras mRNA indicated an increase in confluent and especially in postconfluent cells. Together the findings indicate that normal K-ras p21 activity is associated with growth arrest of lung type II cells, and that the exact contribution of mutated K ras p21 to tumor development remains to be discovered. PMID- 11195464 TI - Mechanisms of aflatoxin B1 lung tumorigenesis. AB - Although aflatoxin B1 (AFB1) is best known as a hepatocarcinogen, the respiratory system can also be a target of this mycotoxin. In isolated lung cells from rabbits and mice, AFB1 is bioactivated by cytochromes P450, primarily in nonciliated bronchiolar epithelial (Clara) cells. However, mutagenesis experiments suggest that the DNA-binding AFB1 epoxide metabolite can leave the cells of origin, and potentially interact with other cell types. Consistent with DNA adduct studies, AFB1-induced AC3F1 mouse lung tumors contain point mutations at guanine residues in K-ras, with the anticipated bias for the A/J allele. Furthermore, following AFB1 treatment but prior to tumor development, K-ras mutations occur preferentially in mouse Clara cells. However, in contrast to findings with other carcinogens, AFB1-induced mouse lung tumors demonstrate frequent, but heterogeneously distributed, overexpression of p53 protein as well as p53 point mutations, suggesting a carcinogen-specific response. Unlike lung tissue from mice and rabbits, human peripheral lung bioactivates AFB1 primarily by prostaglandin H synthase--and/or lipoxygenase-catalyzed cooxidation, with activity concentrated in macrophages. In addition, although glutathione S transferase M1-1 has high specific activity for AFB1 epoxide conjugation, lung tissues from GSTM1-null individuals do not demonstrate diminished rates of conjugation, compared to tissues from GSTM1-positive individuals. In summary, AFB1 tumorigenesis in mice demonstrates unique properties, and processes of bioactivation show significant species differences. PMID- 11195465 TI - Transforming growth factor-beta 1 and its receptors in human lung cancer and mouse lung carcinogenesis. AB - The transforming growth factor-betas (TGF-beta s) are multifunctional proteins that inhibit the proliferation of many epithelial cells through a set of cell protein receptors that includes the TGF-beta type I (RI) and type II (RII) receptors. Loss of growth inhibition by TGF-beta is thought to contribute to the development of many types of tumors. In the present study, we have examined expression of the proteins and mRNAs for TGF-beta 1, TGF-beta RI, and TGF-beta RII in normal human lung, well-characterized non-small cell lung cancer (NSCLC) cell lines, and primary NSCLC specimens. Immunohistochemical staining for TGF beta 1, TGF-beta RI, and TGF-beta RII using specific antibodies in normal human lung showed expression of the 3 proteins in the epithelium of bronchi and bronchioles as well as in alveoli. Differential expression of TGF-beta RI and TGF beta RII proteins was detected in 5 NSCLC cell lines using Western blot analysis, with reduced levels in 3 cell lines. A panel of 45 formalin-fixed and paraffin embedded NSCLC specimens showed positive immunostaining for TGF-beta 1, TGF-beta RI, and TGF-beta RII, with reduced TGF-beta RII in poorly differentiated adenocarcinomas and squamous cell carcinomas and some moderately differentiated adenocarcinomas. In situ hybridization studies conducted with specific riboprobes for TGF-beta 1, TGF-beta RI, and TGF-beta RII showed corresponding localization of expression of the mRNAs in the specimens that showed positive immunostaining for the proteins. To investigate the roles of TGF-beta 1, TGF-beta RI, and TGF beta RII in chemically induced mouse lung tumorigenesis, we examined the expression of their proteins and mRNAs in 2 mouse model systems. Whereas expression of the proteins and mRNAs for TGF-beta 1 and TGF-beta RI was comparable in lung adenomas and bronchioles of A/J mice treated with benzo(alpha)pyrene, decreased immunostaining and hybridization for TGF-beta RII protein and mRNA was detected in 50% of lung adenomas in these mice. Interestingly, expression of TGF-beta 1 and the TGF-beta receptor proteins was similar to that of bronchioles in C57B1/6 mice and their littermates heterozygous for deletion of the TGF-beta 1 gene treated with diethylnitrosamine. These data show that reduced levels of expression of TGF-beta RII occur in some, but not all, human and mouse lung tumors. This suggests that different mechanisms of action, some of which may involve the TGF-beta signaling pathway, may contribute to the progression of lung tumorigenesis. PMID- 11195466 TI - Differential sensitivity to lung tumorigenesis following transplacental exposure of mice to polycyclic hydrocarbons, heterocyclic amines, and lung tumor promoters. AB - Research conducted by this laboratory over the past decade has demonstrated the high susceptibility of the fetus to lung tumor formation following in utero exposure of the resistant C57BL/6 and DBA/2N strains of mice to 3 methylcholanthrene (MC). In this review, we describe our more recent studies on the effects of MC and cotreatment with the lung tumor promoter, butylated hydroxytoluene (BHT), on lung tumor formation in the intermediately susceptible BALB/c strain of mice, and the determination of the potential carcinogenicity of the heterocyclic amine, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in resistant mouse strains. BALB/c mice showed a similar incidence of lung tumors, both in terms of percentage of mice with tumors and number of tumors per mouse, as found in the resistant [D2 x B6D2F1]F2 mice. Ki-ras point mutations were found in 56% (20/36) of BALB/c lung lesions compared with an incidence of 79% in [D2 x B6D2F1]F2 mice. BALB/c lung lesions demonstrated a similar association of Ki-ras mutations with tumor stage. Interestingly, a strain-dependent difference was observed in the mutational spectrum, where 62% and 38% of the lesions in BALB/c mice exhibited G-->C and G-->T transversions, respectively, in contrast with the 16% and 84% incidences observed in [D2 x B6D2F1]F2 mice. BHT had no statistically significant effect on tumor incidence, multiplicity, or Ki-ras mutational spectrum in BALB/c mice treated in utero with MC, although a trend toward increased tumor multiplicity was observed. Finally, experiments initiated to assess the transplacental carcinogenicity of IQ in D2B6F1 mice demonstrated that 1 year after birth, no macroscopically or microscopically visible liver, lung, or colon tumors were found in the transplacentally treated offspring, nor was induction of Cyp1a1, Cyp1b1, or glutathione S-transferases (GSTs) in fetal lung and liver tissues observed. This implies that at least under these experimental conditions, IQ may not be an important transplacental carcinogen. Overall, these data demonstrate that mutagenic damage to Ki-ras is a critical early event mediating murine lung tumorigenesis in both sensitive and resistant strains. Strain-dependent differences in the Ki-ras mutational spectrum may be associated with their differential susceptibility to lung tumor initiation. PMID- 11195467 TI - Inhibition of COX-2 and induction of apoptosis: two determinants of nonsteroidal anti-inflammatory drugs' chemopreventive efficacies in mouse lung tumorigenesis. AB - Recent studies suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit lung tumorigenesis under conditions that are immunosuppressive. We hypothesized that this inhibition of mouse lung tumorigenesis requires induction of apoptosis and inhibition of COX (cyclooxygenase)-1, COX-2, and the incidence of K-ras mutation. The NSAIDs used in this study include acetylsalicylic acid (ASA) that is anti-inflammatory with COX-1 and COX-2 inhibition and N-[2 (cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS398) that is a specific COX 2 inhibitor. We have previously demonstrated that ASA (147 and 294 mg/kg diet) and NS398 (7 mg/kg diet) inhibited lung tumorigenesis by 31%, 44%, and 34%, respectively, in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-treated A/J mice. No difference in the incidence and types of K-ras mutations was found between the lung tumors treated with NNK and those treated with NNK/ASA and NNK/NS398. In NNK-treated mice, ASA (394 mg/kg diet) or NS398 significantly increased the apoptotic index, from 0.07 to 0.30 or to 0.33, respectively. ASA (294 mg/kg diet) and NS398 also inhibited the expression of COX-2. Finally, modulation of gene expression by NS398 and ASA (294 mg/kg diet) was determined using Atlas cDNA expression arrays. Expression of cyclin B2 was decreased and expression of Fas-L and BAD were increased in lung tissues treated with both NS398 and ASA. Treatment with NS398 also increased expression of p57kip2 and myosin. These genes modulated by NSAIDs may play a role in mediating the observed chemopreventive effects of the NSAIDs in the mouse lung. Our results demonstrate that lung tumor prevention with NSAIDs involve both the induction of apoptosis and the inhibition of COX-2 expression. PMID- 11195468 TI - Successful and not so successful chemoprevention of tobacco smoke-induced lung tumors. AB - Strain A/J mice underwent whole body exposure for 6 hours a day, 5 days a week, for 5 months to a mixture of cigarette sidestream and mainstream smoke (89%-11%; total suspended particulates 80-150 mg/m3), then were kept for another 4 months in air before being killed for scoring of lung tumors. In 7 independent experiments, lung tumor multiplicity was significantly increased in all 7 trials and lung tumor incidence in 5. When animals were kept for 9 months in smoke, lung tumor multiplicity was not significantly higher than in controls, although lung tumor incidence was. The following chemopreventive agents were evaluated: green tea, phenethyl isothiocyanate (PEITC), acetylsalicylic acid (ASA), N acetylcysteine (NAC), p-XSC (1,4-phenylenebis[methylene]selenocyanate), d limonene (DL), and a mixture of PEITC and BITC (benzyl isothiocyanate). In animals exposed to tobacco smoke, none of these agents reduced lung tumor multiplicity or incidence. As a control, the effects of the same agents were examined in A/J mice initiated with 4-(methylnitrosamino)-1-(3pyridyl)-1-butanone (NNK) or urethane. In mice injected with NNK, green tea and ASA did not reduce lung tumor multiplicities and NAC had no effect on urethane-induced lung tumors, whereas PEITC, p-XSC and DL reduced NNK-induced tumor multiplicities to 20% to 50% of control values. On the other hand, dietary mixture of myoinositol and dexamethasone was not only highly protective against NNK, but reduced lung tumor multiplicities and incidence in smoke-exposed animals to control values. This effect was also seen when the animals were fed the myo-inositol-dexamethasone mixture once they were removed from smoke. It is concluded that in animal studies it might be preferable to evaluate the effectiveness of putative chemopreventive agents against full tobacco smoke rather than against selected model compounds. The observations made with myo-inositol-dexamethasone suggest that people who have recently quit smoking might benefit the most from active chemoprevention. PMID- 11195469 TI - Chemoprevention of vinyl carbamate-induced lung tumors in strain A mice. AB - The ability of potential chemopreventive agents to prevent vinyl carbamate induced lung tumors was determined in 2 different experiments. Female strain A mice administered intraperitoneally either a single injection of 60 mg/kg vinyl carbamate that induced 24.0 +/- 1.72 tumors/mouse at 24 weeks or 2 injections of 16 mg/kg vinyl carbamate each (32 mg/kg total dose) that induced 43.2 +/- 3.2 tumors/mouse at 20 weeks. Lung carcinomas were found as early as 16 weeks. Dexamethasone and piroxicam provided in the diet were found to significantly inhibit lung tumors induced by 60 mg/kg vinyl carbamate at 24 weeks whereas myo inositol also provided in the diet, did not significantly inhibit tumor formation. In animals given 6 16-mg/kg doses of vinyl carbamate, tumor multiplicity was reduced roughly 25% by alpha-difluoromethylornithine and green tea and reduced 50% by dexamethasone and piroxicam. Combinations of these agents were also tested using a total dose of 32 mg/kg of vinyl carbamate. Although alpha-difluoromethylornithine and green tea did not result in a significant inhibition of lung tumor formation if used alone, the combination of alpha difluoromethylornithine and green tea resulted in a significant reduction of tumor multiplicity. The combinations of alpha-difluoromethylornithine or green tea with either dexamethasone or piroxicam or the combination of dexamethasone and piroxicam did not decrease tumor multiplicity greater than achieved by dexamethasone and piroxicam alone. In summary, selected chemopreventive agents previously shown to inhibit lung tumors by other chemical carcinogens also inhibited vinyl carbamate-induced lung tumors. PMID- 11195470 TI - Chemopreventive efficacy of promising farnesyltransferase inhibitors. AB - The studies presented were designed to test the efficacy of farnesyltransferase inhibitors (FTIs) as potential chemopreventive compounds in the mouse lung tumor model, and in tumor cell lines. The compounds included manumycin, gliotoxin, dihydroepiandrosterone (DHEA), perillyl alcohol (POH), and FTI-276. Each of these compounds had the potential, based on in vitro and limited in vivo evidence, to inhibit mouse lung tumorigenesis. In vitro studies were conducted with both K-ras transformed NIH-3T3 cells and mouse lung tumor epithelial cell lines. We utilized 2 primary mouse lung tumor models that reliably produce lung tumors with an oncogenic K-ras mutation when induded by 4-(methylnitrosoamino)-1-(3-pyridyl)-1 butanone (NNK). Manumycin, gliotoxin, DHEA, and POH were administered 3 times per week peritoneally (i.p.), starting 1 week prior to carcinogen treatment, and throughout the test period (4.5 months). FTI-276 was delivered daily for 4 months by a time-release pellet method. Both the manumycin and gliotoxin treatment groups demonstrated 100% incidence and an increase in tumor multiplicity over control, of 66% and 58% increase respectively (P < .05). Although DHEA showed no significant chemopreventive effect, POH treatment demonstrated a 22% reduction in tumor incidence (P < .05) and a 58% reduction in tumor multiplicity (P < .05). Finally, FTI-276 reduced both the tumor multiplicity by 41.7% (P < .005), and the total tumor volume/burden per mouse by 79.4% (P < .0001). The apoptotic index in FTI-276-treated tumors showed an increase of 77% over control tumors (P < .05). In vitro, all compounds demonstrated growth inhibition at a dose-response manner; however, manumycin, gliotoxin, and DHEA demonstrated an initial increase in growth rate at lower doses. In summary, we have shown that POH and FTI-276 are chemopreventive in a primary mouse lung tumor model. In contrast, DHEA was not significantly chemopreventive at the dosage utilized, and treatment of an immunocompetent host with manumycin or gliotoxin demonstrated a significant increase in tumorigenicity over carcinogen control. PMID- 11195471 TI - Is the combination of ibuprofen and caffeine effective for the treatment of a tension-type headache? PMID- 11195472 TI - What is the most cost-effective screening regimen for colon cancer? PMID- 11195473 TI - Are antidepressants effective in the treatment of fibromyalgia, and is this effect independent of depression? PMID- 11195474 TI - Clinical inquiries. What is a reasonable initial approach to the patient with fatigue? PMID- 11195475 TI - Clinical inquiries. Is surgery effective for reducing symptoms in adults with obstructive sleep apnea? PMID- 11195476 TI - Does the family APGAR effectively measure family functioning? AB - BACKGROUND: The Family APGAR has been widely used to study the relationship of family function and health problems in family practice offices. METHODS: Data were collected from 401 pediatricians and family physicians from the Pediatric Research in Office Settings network and the Ambulatory Sentinel Practice Network. The physicians enrolled 22,059 consecutive office visits by children aged 4 to 15 years. Parents completed a survey that included the Family APGAR and the Pediatric Symptom Checklist. Clinicians completed a survey that described child psychosocial problems, treatments initiated or continued, and specialty care referrals. RESULTS: Family dysfunction on the index visit often differed from dysfunction at follow-up (kappa=0.24). Only 31% of the families with positive Family APGAR scores at baseline were positive at follow-up, and only 43% of those with positive scores at follow-up had a positive score at the initial visit. There were many disagreements between the Family APGAR and the clinician. The Family APGAR was negative for 73% of clinician-identified dysfunctional families, and clinicians did not identify dysfunction for 83% of Family APGAR-identified dysfunctions (kappa=0.06). CONCLUSIONS: Our data do not support the use of the Family APGAR as a measure of family dysfunction in the primary care setting. Future research should clarify what it does measure. PMID- 11195477 TI - The common cold in patients with a history of recurrent sinusitis: increased symptoms and radiologic sinusitislike findings. AB - BACKGROUND: We evaluated whether the symptoms and signs and radiologic findings during a common cold are similar in patients who have and have not suffered from recurrent sinusitis. METHODS: We recruited 2 series of volunteer cases from February 1, 1996, to December 31, 1996. Twenty-three adults who claimed to have suffered from recurrent sinusitis and 25 who had never had sinusitis were examined during the period of a self-diagnosed cold of 48 to 96 hours' duration and again after 21 days. Symptom scores were recorded, nasoendoscopy and computed tomography scans were performed, and viral and bacterial specimens were taken. RESULTS: The patients with a history of sinusitis had significantly higher symptom scores than the control patients (P=.04) and had radiologic sinusitislike changes more often (65% [15] vs 36% [9]; difference 29% [95% confidence interval, 2%-56%]; P=.04). The viral etiology of the common cold (verified in 67% of the episodes) was similar in both groups. Pathogenic bacteria were isolated from the middle meatus in 24% (6) of the control patients and only 9% (2) of the sinusitis prone patients (P=.15). On the basis of the symptomatology, radiologic findings, and bacterial cultures only 2 patients in the sinusitis-prone group should have been treated with antimicrobials. CONCLUSIONS: Some patients are susceptible to both sinusitislike symptoms and radiologic findings during viral common colds. This may cause them to consult their physicians earlier and more often during viral colds, which may result in unnecessary antibiotic treatments. Nasopharyngeal bacteriological cultures may prove to be useful in ruling out bacterial sinusitis. PMID- 11195478 TI - Use and perceptions of antibiotics for upper respiratory infections among college students. AB - BACKGROUND: Upper respiratory infections (URIs) are mainly viral in nature, rendering antibiotics ineffective. Little is known about what college students believe concerning the effectiveness of antibiotics as a treatment for URIs. METHODS: Students (n=425) on 3 college campuses were surveyed using a survey describing 3 variations in presentation of an uncomplicated URI. Participants were questioned about their likelihood of using a variety of treatments for the URI and about their likelihood of seeking a physician's care. RESULTS: The percentage of students endorsing antibiotic use differed significantly by symptom complex. Likelihood of seeking medical care also differed significantly across symptom groups, with greater endorsement in the discolored nasal discharge and low-grade fever scenarios. Stepwise multiple regression analysis revealed that belief in antibiotic effectiveness for cold symptoms decreased with tic and Therapeutic increasing years of higher education. Likelihood of antibiotic use across different scenarios increased with age. Likelihood of seeking care across different scenarios was related to type of health insurance and belief in antibiotic effectiveness. CONCLUSIONS: Undergraduate college students show poor recognition of typical presentations of the common cold and have misconceptions about effective treatment. Although increasing years of college correlated with decreasing belief in antibiotics' effectiveness for a cold, more health education at the college level is recommended. PMID- 11195479 TI - Acute rhinosinusitis: a diagnostic and therapeutic challenge. PMID- 11195480 TI - Mental illness, functional impairment, and patient preferences for collaborative care in an uninsured, primary care population. AB - OBJECTIVE: Our goal was to compare the prevalence of mental illness and its impact on functional status in an indigent uninsured primary care population with a general primary care sample. We also hoped to assess patient preferences about mental health and medical service integration. STUDY DESIGN: We compared a survey of consecutive primary care adults in April and May 1999 with a 1997-98 survey of 3000 general population primary care patients. Both studies used the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire and the 20-question Medical Outcomes Study Short Form. POPULATION: The patients were from a private nonprofit primary care clinic in Grand Junction, Colorado, that served only low income uninsured people. We approached a total of 589 consecutive patients and enrolled 500 of them. MAIN OUTCOME MEASURE: The main outcomes were the prevalence of psychiatric illnesses and the relationship with functional impairment. We compared our findings with a more generalizable primary care population. RESULTS: This low-income uninsured population had a higher prevalence of 1 or more psychiatric disorders (51% vs 28%): mood disorders (33% vs 16%), anxiety disorders (36% vs 11%), probable alcohol abuse (17% vs 7%), and eating disorders (10% vs 7%). Having psychiatric disorders was associated with lower functional status and more disability days compared with not having mental illness. Patients indicated a preference for mental health providers and medical providers to communicate about their care. CONCLUSIONS: This low-income uninsured primary care population has an extremely high prevalence of mental disorders with impaired function. It may be important in low-income primary care settings to include collaborative care designs to effectively treat common mental disorders, improve functional status, and enhance patient self-care. PMID- 11195481 TI - Becoming an information master: using "medical poetry" to remove the inequities in health care delivery. AB - In response to the spiraling costs, the US populace, for now, has chosen to ration health care by choosing who can receive it rather than what services are provided. Changing this approach will require an organized national policy and will be difficult. Clinicians must accept that providing minimally beneficial but not absolutely necessary care to their patients increases cost without significantly improving quality, and results in more people who lack adequate health care. The public must accept that exclusively focusing health care decisions on individuals places patients in conflict with their community, their family, and, eventually, themselves. Effectively using valid Patient-Oriented Evidence that Matters (POEMs) will give family physicians the tools necessary to improve the value of health care services. Family physicians are in the unique position to guide the necessary changes in health care delivery to resolve these conflicts and to be leaders in this process. PMID- 11195482 TI - The evaluation and treatment of adults with gastroesophageal reflux disease. AB - Gastroesophageal reflux disease (GERD) is defined as symptoms or tissue damage that results from the abnormal reflux of gastric contents into the esophagus. A systematic review of population-based studies estimates that heartburn or regurgitation symptoms occur in 21% to 59% of the population during a given year. The frequency of GERD in specific populations is provided in Table 1. Although only 1 in 5 patients with upper intestinal symptoms that occur at least weekly seeks medical attention, nearly 1% of all visits to a family physician's office are for GERD or related conditions. GERD significantly affects the quality of patients' lives. In a survey of patients presenting for upper endoscopy with symptoms of at least 3 months' duration, those with a diagnosis of GERD reported low scores at baseline for general well-being. Fortunately, follow-up data reported 4 weeks after treatment note improvement in gastrointestinal symptoms, general well-being, general health, vitality, and depression. PMID- 11195483 TI - Does use of an instant hand sanitizer reduce elementary school illness absenteeism? PMID- 11195484 TI - Is the sweeping of membranes a useful intervention in conjunction with induction of labor in term pregnancy? PMID- 11195485 TI - Can a clinical rule accurately predict whether a patient has strep throat? PMID- 11195486 TI - Is budesonide or nedocromil superior in the long-term management of mild to moderate asthma in children? PMID- 11195487 TI - Smoking, hypertension, and erectile dysfunction. PMID- 11195489 TI - Old stone face. PMID- 11195488 TI - Preventing acute mountain sickness. PMID- 11195490 TI - Can vaginal misoprostol be administered 1 to 3 days after mifepristone without loss of efficacy or an increase in adverse events? PMID- 11195491 TI - Surface plasmon resonance imaging measurements of DNA and RNA hybridization adsorption onto DNA microarrays. AB - Surface plasmon resonance (SPR) imaging is a surface-sensitive spectroscopic technique for measuring interactions between unlabeled biological molecules with arrays of surface-bound species. In this paper, SPR imaging is used to quantitatively detect the hybridization adsorption of short (18-base) unlabeled DNA oligonucleotides at low concentration, as well as, for the first time, the hybridization adsorption of unlabeled RNA oligonucleotides and larger 16S ribosomal RNA (rRNA) isolated from the microbe Escherichia coli onto a DNA array. For the hybridization adsorption of both DNA and RNA oligonucleotides, a detection limit of 10 nM is reported; for large (1,500-base) 16S rRNA molecules, concentrations as low as 2 nM are detected. The covalent attachment of thiol-DNA probes to the gold surface leads to high surface probe density (10(12) molecules/cm2) and excellent probe stability that enables more than 25 cycles of hybridization and denaturing without loss in signal or specificity. Fresnel calculations are used to show that changes in percent reflectivity as measured by SPR imaging are linear with respect to surface coverage of adsorbed DNA oligonucleotides. Data from SPR imaging is used to construct a quantitative adsorption isotherm of the hybridization adsorption on a surface. DNA and RNA 18 mer oligonucleotide hybridization adsorption is found to follow a Langmuir isotherm with an adsorption coefficient of 1.8 x 10(7) M(-1). PMID- 11195492 TI - Electrochemically actuated mercury pump for fluid flow and delivery. AB - This paper describes the development of a prototype pumping system with the potential for incorporation into miniaturized, fluid-based analytical instruments. The approach exploits the well-established electrocapillarity phenomena at a mercury/electrolyte interface as the mechanism for pump actuation. That is, electrochemically induced changes in the surface tension of mercury result in the pistonlike movement of a mercury column confined within a capillary. We present herein theoretical and experimental assessments of pump performance. The design and construction of the pump are detailed, and the potential attributes of this design, including the generated pumping pressure, flow rate, and power consumption, are discussed. The possible miniaturization of the pump for use as a field-deployable, fluid-delivery device is also briefly examined. PMID- 11195493 TI - Continuous cell introduction for the analysis of individual cells by capillary electrophoresis. AB - Instrumentation for high-throughput analysis of single cells by capillary electrophoresis is described. A flow-based interface that uses electroosmotic flow (EOF) provides continuous injection of intact cells through an introduction capillary into a cell lysis junction and migration of the resulting cell lysate through a separation capillary for analysis. Specifically, two capillaries were coupled together with 5-mm-long Teflon tubing to create a approximately 5-microm gap, and the junction was immersed in a buffer reservoir. High voltage was applied across both capillaries so that cells were continuously pumped into the first capillary by EOF. Individual cells were lysed on-column at the junction without detergents, presumably owing to mechanical disruption caused by a dramatic change in flow properties at the gap. After each cell was lysed at the junction, the major proteins hemoglobin and carbonic anhydrase were separated by capillary electrophoresis and the resultant analyte zones were detected by laser induced native fluorescence using 275-nm excitation. The detection limits of hemoglobin and carbonic anhydrase were 37 and 1.6 amol, respectively, which correlate well with the literature. The instrumentation was evaluated with intact red blood cells. The averaged time for complete analysis (i.e., continuous injection, lysis, separation, and detection) of one human erythrocyte was less than 4 min with this capillary-based setup. Moreover, this instrumentation simplifies the introduction of individual, intact cells without the use of a microscope. PMID- 11195494 TI - Selected reaction monitoring LC-MS determination of idoxifene and its pyrrolidinone metabolite in human plasma using robotic high-throughput, sequential sample injection. AB - The generation of large numbers of samples during early drug discovery has increased the demand for rapid and selective methods of analysis. Liquid chromatography-tandem mass spectrometry (LC-MS-MS), because of its sensitivity, selectivity, and robustness, has emerged as a powerful tool in the pharmaceutical industry for many analytical needs. This work presents a high-throughput selected reaction monitoring LC-MS bioanalytical method for the determination of idoxifene, a selective estrogen receptor modulator, and its pyrrolidinone metabolite in clinical human plasma samples. The described method uses short, small-bore columns, high flow rates, and elevated HPLC column temperatures to perform LC separations of idoxifene and its metabolite within 10 s/sample. Sequential injections were accomplished with a 215/889 multiple probe liquid handler (Gilson, Inc.), which aspirates eight samples simultaneously and performs its rinse cycle parallel to sample injection, resulting in minimum lag time between injections. This high-throughput method was applied to the determination of idoxifene and its metabolite in clinical human plasma samples. Sample preparation employed liquid/liquid extraction in the 96-well format. Method validation included determination of intra- and interassay accuracy and precision values, recovery studies, autosampler stability, and freeze-thaw stability. The LOQ obtained was 10 ng/mL for idoxifene and 30 ng/mL for the metabolite. Using idoxifene-d5 as an internal standard, idoxifene showed acceptable accuracy and precision values at QC level 1 (QC1, 15 ng/mL), level 2 (QC2, 100 ng/mL), and level 3 (QC3, 180 ng/mL) (85.0% accuracy +/- 12.0% precision, 95.1 +/- 4.9%, and 90.3 +/- 4.7%, respectively). The pyrrolidinone metabolite also showed acceptable accuracy and precision values (using no internal standard for quantitation) at QC1 (60 ng/mL), QC2 (100 ng/mL), and QC3 (180 ng/mL) (104.9 +/- 14.4%, 91.1 +/- 13.0%, and 90.8 +/- 12.2%, respectively). The validated method was applied to the analysis of 613 human clinical plasma samples. An average run time of 23 s/sample (approximately 37 min/ 96-well plate or over 3,700 sample/day) was achieved. The successful validation presented indicates that rapid methods of analysis can efficiently and reliably contribute to the fast sample turnaround required for high sample number generating processes. PMID- 11195495 TI - Mercury micropumps. PMID- 11195496 TI - Microfluidic device for combinatorial fusion of liposomes and cells. AB - We describe an electrofusion-based technique for combinatorial synthesis of individual liposomes. A prototype device with containers for liposomes of different compositions and a fusion container was constructed. The sample containers had fluid contact with the fusion container through microchannels. Optical trapping was used to transport individual liposomes and cells through the microchannels into the fusion container. In the fusion container, selected pairs of liposomes were fused together using microelectrodes. A large number of combinatorially synthesized liposomes with complex compositions and reaction systems can be obtained from small sets of precursor liposomes. The order of different reaction steps can be specified and defined by the fusion sequence. This device could also facilitate single cell-cell electrofusions (hybridoma production). This is exemplified by fusion of transported red blood cells. PMID- 11195497 TI - "Four-decay" DNA sequencing. PMID- 11195498 TI - Diffusion-based calibration for SPME analysis of aqueous samples. AB - When an SPME fiber is exposed for a short period of time to a flowing fluid sample, the amount of extracted analyte depends on its diffusion coefficient in the matrix medium, and it can be correlated to its concentration using a simple mathematical model. This work discusses the extension of this approach, already validated for gaseous samples and SPME fibers coated with strong adsorbent coatings, to the diffusion-based quantification of analytes present in aqueous samples. Dilute aqueous solutions of aromatic hydrocarbons were used as model samples and vials were modified to use conventional magnetic agitation with controlled tangential flow of the test solution around the fiber. It was demonstrated that, with proper selection of the stirring speed and sampling time, the same diffusion-based quantitative model used for gas samples could be employed. Under optimal conditions, the concentrations of the evaluated aromatic hydrocarbons were estimated with relative standard deviations between 0.8 and 3.6% and without deviation from the expected values within this precision range. Considering the extraction times involved, between 30 and 60 s, the approach here presented is the fastest possible technique for direct extraction of analytes from liquid samples. PMID- 11195499 TI - Argentometric titration for the determination of liquid chromatographic injection reproducibility. AB - The reproducibility of autosamplers for high-performance liquid chromatography can be checked by the injection of a sodium chloride solution without an installed column. The dispensed chloride plug is analyzed quantitatively by argentometric titration. If the titration can be performed with high enough precision, the autosampler performance is investigated without additional effects. Experiments with a 20-microL loop were performed. We found the following repeatabilities (relative standard deviations): titration, 0.07%; 10-microL "pull loop" injection (partial filling of the loop), 0.6%; and 20-microL "full loop" injection, 0.1%. In contrast to these data, the relative standard deviations obtained from chromatographic peaks include the steps of injection, separation, detection, and integration without any knowledge of the individual contributions. Such values are higher; we found for chromatographic peak areas of parabens 2% under pull loop conditions and 0.17% by full loop. The titration approach allows the determination of the contribution of the injection to the uncertainty budget of a liquid chromatographic analysis. PMID- 11195500 TI - Chip-based mosaic immunoassays. PMID- 11195501 TI - Trace atmospheric gases on a shoestring. PMID- 11195502 TI - Phosphopeptide/phosphoprotein mapping by electron capture dissociation mass spectrometry. AB - Of methods for dissociation of multiply charged peptide and protein ions, electron capture dissociation (ECD) has the advantages of cleaving between a high proportion of amino acids, without loss of such posttranslational modifications as glycosylation and carboxylation. Here this capability is successfully extended to phosphorylation, for which collisionally activated dissociation (CAD) can cause extensive loss of H3PO4 and HPO3. As shown here, these losses are minimal in ECD spectra, an advantage for measuring the degree of phosphorylation. For phosphorylated peptides, ECD and CAD spectra give complementary backbone cleavages for identifying modification sites. For a 24-kDa heterogeneous phosphoprotein, bovine beta-casein, activated ion ECD cleaved 87 of 208 backbone bonds that identified a phosphorylation site at Ser-15, and localized three more among Ser-17,-18, -19, and -22 and Thr-24, and the last among four other sites. This is the first direct site-specific characterization of this key post translational modification on a protein without its prior degradation, such as proteolysis. PMID- 11195503 TI - Calixarenes: designer ligands for chemical sensors. PMID- 11195504 TI - A method for determination of ion distribution within electrosprayed droplets. AB - A simplified method for determination of ion distribution within electrospray ionization droplets has been developed. The method is based on an electrospray ionization mass spectrometry equilibrium partitioning model recently developed by Enke (Enke, C. G. Anal. Chem. 1997, 69, 4885-4893). This "simple" method required only two samples to be analyzed at each solution composition compared to the method previously reported. Furthermore, as the same m/z value is monitored in both experiments, possible effects of the mass-dependent ion transmission in the quadrupole were eliminated. Tetra-alkylammonium compounds with variable hydrophobicity were used as model compounds and the effect of methanol-water composition in the electrosprayed solution was studied. It was found, as expected, that the signal optimized at a high content of methanol in the electrosprayed solution. The distribution coefficient for analyte ions between the droplet surface and bulk solution maximize, however, at a lower content of methanol in the electrosprayed solution. PMID- 11195506 TI - Microwave-enhanced chemistry. PMID- 11195505 TI - Analysis of protein phosphorylation by capillary liquid chromatography coupled to element mass spectrometry with 31P detection and to electrospray mass spectrometry. AB - A method for phosphopeptide identification by capillary liquid chromatography (muLC) interfaced alternatively to element mass spectrometry (inductively coupled plasma mass spectrometry, ICPMS) and to electrospray ionization mass spectrometry (ESI-MS) is described. ICPMS is used for 31P detection and ESI-MS provides the corresponding molecular weight information. Alignment of the two separate muLC runs is performed using the baseline distortion at the elution front, which shows up in both muLC-ICPMS and muLC-ESI-MS. Both a quadrupole and a magnetic sector field mass analyzer were used in combination with ICP. The detection limit achieved for the muLC-ICP-HRMS runs is approximately 0.1 pmol of phosphopeptide injected. Without any further precautions, contamination by phosphate-containing compounds at this level was found to be uncritical. The method is demonstrated for the analysis of a complex mixture of synthetic phosphopeptides and a set of tryptic digests of three phosphoproteins. These include beta-casein, activated human MAP kinase ERK1, and protein kinase A catalytic subunit. The tryptic phosphopeptides of these proteins could all be detected and identified by our new strategy. Analysis of three fractions of protein kinase A catalytic subunit with different phosphorylation status gives direct access to the order in which the phosphorylation of the four phosphorylation sites occurs. The two most important aspects of using muLC-ICPMS with 31P detection for phosphopeptide identification are (i) that a high selectivity is achieved and (ii) that the signal intensity is independent of the chemical form of phosphorus and directly proportional to the molar amount of 31P in the muLC eluate. Thus, muLC-ICPMS with 31P detection is introduced as a new, robust, and specific method in phosphoproteomics. PMID- 11195507 TI - Determination of alkylbenzyldimethylammonium chlorides in river water and sewage effluent by solid-phase extraction and gas chromatography/mass spectrometry. AB - This study presents a modified method to analyze alkylbenzyldimethylammonium chlorides (ABDACs) in river water and sewage effluent. The method involves mixed samples with linear alkylbenzenesulfonates (LAS) as a counterion to enhance the extraction of ABDAC residues from an RP-18 solid-phase cartridge by formation of hydrophobic ion-pair complexes. The ABDACs were then eluted with methanol-ethyl acetate (1:1, v/v) and formed to their corresponding alkyldimethylamines by the Hofmann degradation with potassium tert-butoxide. The alkyldimethylamines were then identified and quantitated by gas chromatograph/mass spectrometry (GC/MS). The results indicate that, in the presence of LAS, debenzylation of ABDACs occurs selectively at a temperature higher than 90 degrees C to produce the corresponding nonionic alkyldimethylamines. The method proposed herein provides a high precision and sensitivity for ABDACs, to quantitation at < or =0.1 microg/L in 500 mL of the water samples. The average recovery of ABDAC spiked water samples was 95% with relative standard deviations (RSD, n = 7) of 9%. The RSDs of three replicate environmental sample analyses ranged from 5 to 11%. Direct HPLC method was applied to evaluate the GC/MS method, and compatible results were observed. PMID- 11195508 TI - Mixing electrochemistry with microscopy. PMID- 11195509 TI - Determination of mycophenolic acid and mycophenolate mofetil by high-performance liquid chromatography using postcolumn derivatization. AB - An efficient method to lower the optical detection limit is described using the displacement of an absorption and emission band of an analyte after a polarity change in different solvents. This solvatochromic effect was used in a RP-HPLC assay for the fluorescence detection of mycophenolic acid (6-(4-hydroxy-6-methoxy 7-methyl-3-oxo-5-phthalanyl)-4-methyl-4-hexenoic acid, MPA) and the prodrug mycophenolate mofetil (MMF), the N-(2-hydroxyethyl)morpholino ester of MPA. The rational to use fluorescence detection is based on the behavior of MMF and MPA, which fluoresce in a basic medium (pH >9.5). Following a simple protein precipitation, the analytes were separated in an isocratic RP-HPLC system. The postcolumn generation of the phenolate anions of MPA and MMF was achieved by addition of an aqueous sodium hydroxide solution regulated by a newly developed continuous-flow liquid control system. MPAG, not directly accessible for fluorescence detection, was analyzed after enzymatic deglucuronidation to MPA. Compared to published quantification limits for MPA and MMF by UV detection, this method is more than 100-fold more sensitive, with a lower limit of quantification of 45 fmol for both MPA and MMF. PMID- 11195510 TI - The limits of written tests. PMID- 11195511 TI - Sampling and analysis of airborne particulate matter and aerosols using in-needle trap and SPME fiber devices. AB - A needle trap device (NTD) and commercial poly(dimethylsiloxane) (PDMS) 7-microm film thickness solid-phase microextraction (SPME) fibers were used for the sampling and analysis of aerosols and airborne particulate matter (PM) from an inhaler-administered drug, spray insect repellant, and tailpipe diesel exhaust. The NTD consisted of a 0.53-mm o.d. stainless steel needle having 5 mm of quartz wool packing section near the needle tip. Samples were collected by drawing air across the NTD with a Luertip syringe or via direct exposure of the SPME fiber. The mass loading of PM was varied by adjusting the volume of air pulled through the NTD or by varying the sampling time for the SPME fiber. The air volumes ranged from 0.1 to 50 mL, and sampling times varied from 10 s to 16 min. Particulates were either trapped on the needle packing or sorbed onto the SPME fiber. The devices were introduced to a chromatograph/mass spectrometer (GC/MS) injector for 5 min desorption. In the case of the NTD, 10 microL of clean air was delivered by a gas-tight syringe to aid the introduction of desorbed analytes. The compounds sorbed onto particles extracted by the SPME fiber or trapped in the needle device were desorbed in the injector and no carry-over was observed. Both devices performed well in extracting airborne polycyclic aromatic hydrocarbons (PAHs) in diesel exhaust, triamcinolone acetonide in a dose of asthma drug and DEET in a dose of insect repellant spray. Results suggest that the NTDs and PDMS 7-microm fibers can be used for airborne particulate sampling and analysis, providing a simple, fast, reusable, and cost-effective screening tool. The advantage of the SPME fiber is the open-bed geometry allowing spectroscopic investigations of particulates; for example, with Raman microspectroscopy. PMID- 11195512 TI - Polypyrrole-coated capillary coupled to HPLC for in-tube solid-phase microextraction and analysis of aromatic compounds in aqueous samples. AB - In-tube solid-phase microextraction (SPME) based on a polypyrrole (PPY)-coated capillary was investigated for the extraction of aromatic compounds from aqueous solutions. The PPY-coated capillary was coupled on-line to HPLC that was programmed with an autosampler to achieve automated in-tube SPME and HPLC analysis. Three groups of aromatics, including both polar and nonpolar compounds, were examined. The results demonstrated that the PPY coating had a higher extraction efficiency than the currently used commercial capillary coatings, especially for polycyclic aromatic compounds and polar aromatics due to the increasing pi-pi interactions, interactions by polar functional groups, and hydrophobic interactions between the polymer and the analytes. In addition to the functional groups in the PPY coating, which contributed to the higher extraction efficiency and selectivity toward analytes, the coating's porous surface structure,which was revealed by electron microscopy experiments, provided a high surface area that allowed for high extraction efficiency. It was found that the extraction efficiency and selectivity could be tuned by changing the coating thickness. The preliminary study of the extraction mechanism indicated that analytes were extracted onto the PPY coating mainly by an adsorption mechanism. The method was used for the extraction and analysis of both polar and nonpolar aromatics in aqueous samples. PMID- 11195513 TI - Short-wave near-infrared spectroscopy of biological fluids. 1. Quantitative analysis of fat, protein, and lactose in raw milk by partial least-squares regression and band assignment. AB - The present study has aimed at providing new insight into short-wave near infrared (NIR) spectroscopy of biological fluids. To do that, we analyzed NIR spectra in the 800-1,100-nm region of 100 raw milk samples. The contents of fat, proteins, and lactose were predicted by partial least-squares (PLS) regression and band assignment in that region was investigated based upon PLS loading plots and regression coefficients. For the fat prediction, the whole set of samples was divided into two groups and the fat concentration was predicted for the samples that were not included in the calibration procedures. The correlation coefficient and root-mean-square error of prediction (RM-SEP) in the better prediction run were found to be 0.996 and 0.087 wt %, respectively. Assignment of the bands due to fat was proposed based upon the regression coefficients and PLS loading weights, and the importance of a pretreatment in the prediction was discussed. Milk proteins also yielded sufficient correlation coefficients and RMSEP although the contributions of protein bands to the milk spectra were much smaller than those of the fat bands. The sizes of the calibration models for protein prediction were considered. This is the first time that good correlation coefficients and RMSEP of proteins have ever been obtained for the short-wave NIR spectra of milk. For lactose, noisy regression coefficients with limited prediction ability were obtained. Band assignment was investigated also for bands due to proteins and lactose. We propose the detailed band assignment for the short-wave NIR region useful for various biological fluids. The results presented here demonstrate that the short-wave NIR region is promising for the fast and reliable determination of major components in biological and biomedical fluids. PMID- 11195514 TI - An approach for analysis of protein toxins based on thin films of lipid mixtures in an optical biosensor. AB - Biological membrane-like lipid films were deposited on the sensing surface in an optical biosensor instrument. The membranes were mixtures of biologically occurring lipids. Eight surfaces were prepared, some of which contained various glycolipids as minor components. One was supplemented with membrane proteins. The binding of six protein toxins (cholera toxin, cholera toxin B subunit, diphtheria toxin, ricin, ricin B subunit, staphylococcal enterotoxin B) and of bovine serum albumin at pH 7.4 and pH 5.2 to each of the sensor surfaces was studied. Each of the seven proteins gave a distinct binding pattern. The assay is rapid and simple, with no need for reagents. The lipid sensor surface is readily regenerated after binding and very stable. The concept with mixed lipid layers and assays at different pHs gives numerous combinations and could be applicable for developing a sensor for protein toxins. PMID- 11195515 TI - Micromosaic immunoassays. AB - Immunoassays are widely used for medical diagnostics and constitute the principal method of detecting pathogenic agents and thus of diagnosing many diseases. These assays, which are most often performed in well plates, would be greatly improved by a practical method to pattern a series of antigens on a flat surface and to localize their binding to many analytes. But no obvious method exists to expose a planar surface successively to a series of antigens and analytes. Here, we present miniaturized mosaic immunoassays based on patterning lines of antigens onto a surface by means of a microfluidic network (muFN). Solutions to be analyzed are delivered by the channels of a second muFN across the pattern of antigens. Specific binding of the target antibodies with their immobilized antigens on the surface results in a mosaic of binding events that can readily be visualized in one screening using fluorescence. It is thus possible to screen solutions for antibodies in a combinatorial fashion with great economy of reagents and at a high degree of miniaturization. Such mosaic-format immunoassays are compatible with the sensitivity and reliability required for immunodiagnostic methods. PMID- 11195516 TI - Selectivity behavior and multianalyte detection capability of voltammetric ionophore-based plasticized polymeric membrane sensors. AB - The current response features ofvoltammetric ion-selective polymeric membranes doped with neutral ionophores in view of practical sensor development are elucidated. The membranes are designed to extract ions only under applied external potentials and interrogated by normal-pulse voltammetry and pulsed amperometry. They contain two polarizable interfaces to avoid loss of lipophilic ions at the sample side and to maximize the available potential window. A simple theoretical model is developed that describes the observed current at the end of an uptake pulse to the applied membrane potential, which is the sum of both boundary potentials (at the sample and inner electrolyte side) and the membrane internal iR drop. The results describe how the selectivity of the resulting sensor must be dependent on the applied potential. Evidently, the role of the applied potential is akin to incorporating lipophilic cationic and anionic sites with potentiometric ionophore-based membranes, which are well known to considerably affect membrane selectivity and to define the charge type of the assessed ions. This has important implications for sensor design, as the applied cell potential can be used to tune sensor selectivity. Theory also explains the role of the inner electrolyte on sensor behavior. A maximum measuring range is expected with ions in the inner electrolyte that are difficult to extract into the membrane. This corresponds to Kihara's experimental results and contrasts to common ion-selective electrode practice, where a salt of the analyte ion is normally present in the inner electrolyte. Separate and mixed solution experiments with membranes containing the sodium-selective ionophore tert-butyl calix[4]arene tetramethyl ester and the lithium ionophore ETH 1810 agree very well with theoretical expectations. Multianalyte detection capability with a single sensing membrane is demonstrated in a selectivity-modifying pulsed amperometric detection mode, where each applied voltage yields a different practical selectivity of the sensor. The sensor is altered from being sodium to potassium selective as the magnitude of the applied potential is repetitively varied within the pulse sequence. The sensors show high long-term stability under continuous measuring conditions over 15 h. PMID- 11195517 TI - Liposomes labeled with biotin and horseradish peroxidase: a probe for the enhanced amplification of antigen--antibody or oligonucleotide--DNA sensing processes by the precipitation of an insoluble product on electrodes. AB - Liposomes labeled with biotin and the enzyme horseradish peroxidase (HRP) are used as a probe to amplify the sensing of antigen-antibody interactions or oligonucleotide-DNA binding. The HRP-biocatalyzed oxidation of 4-chloro-1 naphthol (1) in the presence of H2O2, and the precipitation of the insoluble product 2 on electrode supports, are used as an amplification route for the sensing processes. The anti-dinitrophenyl antibody (DNP-Ab) is sensed by a dinitrophenyl-L-cysteine antigen monolayer associated with an Au electrode. A biotinylated anti-IgG-antibody (Fc-specific) is linked to the antigen-DNP-Ab complex, and the biotin-labeled HRP-liposomes associate with the assembly through an avidin bridge. The biocatalyzed precipitation of 2 on the electrode increases the electron-transfer resistances at the electrode-solution interface or the electrode resistance itself. The binding events of the different proteins on the electrode and the biocatalyzed precipitation of 2 on the conductive support are followed by Faradaic impedance spectroscopy or constant-current chronopotentiometry. DNP-Ab concentrations as low as 1 x 10(-11) g x mL(-1) can be detected by this method. The labeled liposomes were also used for the amplified detection of DNA 3. The oligonucleotide 4, complementary to a part of the target DNA 3 that is a model nucleic acid sequence for the Tay-Sachs genetic disorder, is assembled on an Au electrode. Hybridization of the analyte 3 followed by the association of the biotin-tagged oligonucleotide 5 yields a three component double-stranded assembly. Sensing of the analyte 3 is amplified by the association of avidin, the labeled liposomes, and the subsequent biocatalyzed precipitation of 2 on the electrodes. The DNA 3 is detected with a sensitivity that corresponds to 6.5 x 10(-13) M. Faradaic impedance spectroscopy and chronopotentiometry were employed to follow the stepwise assembly of the systems and the electronic transduction of the detection of the analyte DNA 3. PMID- 11195518 TI - Low-affinity complexes. PMID- 11195519 TI - An investigation of the etiology of a mild diarrhea observed in a group of grower/finisher pigs. AB - An investigation into a mild diarrhea in a group of grower/finisher pigs was carried out in order to determine the etiology. A tiamulin injection and a carbadox-medicated ration were given to pens of pigs in a 2 x 2 factorial experimental design. Pens of pigs were assessed a score, based on the consistency of the feces in the pen, each week. The clinical investigation looked for the intestinal pathogens Brachyspira pilosicoli, B. hyodysenteriae, Lawsonia intracellularis, Salmonella spp., Yersinia spp., transmissible gastroenteritis virus, and rotavirus. Despite a rigorous investigation, the diarrhea was not attributed to any pathogen. A mild colitis was noted among pigs necropsied while affected with diarrhea. Improved diagnostic tools may allow a more effective response to an outbreak of mild disease, while at the same time reducing the amount of antimicrobials used in swine production. PMID- 11195521 TI - A survey of the prevalence of Giardia in dogs presented to Canadian veterinary practices. AB - Fecal samples (1216) were collected from dogs presented to 15 veterinary practices across Canada and tested for Giardia by ELISA for group-specific antigen. If positive, the presence of Giardia was confirmed by microscopy. Eighty eight submissions tested positive by ELISA and microscopy. The overall prevalence rate of Giardia was 7.2%. PMID- 11195520 TI - Evaluation of a strategic deworming program in dairy heifers in Quebec based on the use of moxidectin, an endectocide with a long persistency. AB - Two different deworming strategies based on the use of moxidectin, a broad spectrum endectocide with persistency against Ostertagia ostertagi, were evaluated in grazing dairy heifers. Eighty-four heifers unexposed to parasitic infection were randomly allocated to 3 different groups: untreated (Group 1), treated at 3 and 10 weeks after turnout with 0.5 mg/kg/body weight (BW) of topical moxidectin (Group 2), or treated at turnout and 10 weeks later with 0.5 mg/kg/BW of topical moxidectin (Group 3). The heifers were turned out on June 6 (Day 0) to a naturally contaminated pasture divided into 3 sections by an electrical fence. Each group of heifers was put on a different section of pasture. The trial ended when they were housed on October 29 (Day 143). The results of this experiment confirmed the beneficial effect of 2 strategic treatments with moxidectin pour-on under field conditions in Quebec. The parasitological parameters showed a statistical difference in terms of mean fecal egg counts between treated and control groups (ANOVA, P < or = 0.006). After turnout, pasture larval counts were consistently higher for Group 1 compared with counts for Group 2 or 3. All heifer groups gained weight during the trial period, but the weight gain profile of both treated groups was significantly higher than that of the untreated controls (ANOVA, P < 0.03). During the trial period, Group 2 and Group 3 gained 77.7 kg BW and 73.2 kg BW, respectively, while Group 1 gained only 57.9 kg BW, despite the fact that heifers of Group 1 received a greater quantity of supplementary feed while on pasture. PMID- 11195522 TI - Predictive variables for the occurrence of early clinical mastitis in primiparous Holstein cows under field conditions in France. AB - Holstein heifers from 47 dairy herds in France were enrolled in a field study to determine predictors for clinical mastitis within the first month of lactation. Precalving and calving variables (biochemical, hematological, hygienic, and disease indicators) were collected. Early clinical mastitis (ECM) predictive variables were analyzed by using a multiple logistic regression model (99 cows with ECM vs. 571 without clinical mastitis throughout the first lactation). Two variables were associated with a higher risk of ECM: a) difficult calving and b) medium and high white blood cell (WBC) counts in late gestation. Two prepartum indicators were associated with a lower ECM risk: a) medium and high serum concentrations of immunoglobulin G1 (IgG1) and b) high percentage of eosinophils among white blood cells. Calving difficulty and certain biological blood parameters (IgG1, eosinophils) could represent predictors that would merit further experimental studies, with the aim of designing programs for reducing the risk of clinical mastitis in the first lactation. PMID- 11195523 TI - The interpretation of "scientific". PMID- 11195524 TI - Estimating the cost of sea lice to salmon aquaculture in eastern Canada. AB - Parasitic sea lice are serious problems in aquaculture. The true cost of these parasites is unknown. We demonstrate the economic burden imposed by sea lice, so that researchers, aquatic specialists, and policy makers can approximate the economic cost of this problem and work towards developing alternative control methods. PMID- 11195525 TI - A survey of demographics and information demands of dairy producers. AB - Survey responses from 75 randomly selected dairy producers on Prince Edward Island were summarized to obtain a demographic picture of the dairy industry in this province and to determine information management practices and demands for the future. The results indicate a preparedness for dairy production in the future. PMID- 11195526 TI - Are dry cat foods contributing to the increased occurrence of certain feline diseases? PMID- 11195527 TI - Causes of sudden and unexpected death in cats: a 10-year retrospective study. PMID- 11195528 TI - Hypertrophic osteodystrophy in a Great Dane puppy. AB - An intact male, Great Dane puppy was evaluated for weakness, lethargy, reluctance to move, and inability to stand. Hypertrophic osteodystrophy was diagnosed based on clinical and radiographic findings. Clinical signs, radiographic lesions, gross pathology, histopathology, etiology, and treatment of the disease are discussed. PMID- 11195529 TI - An ethicist's commentary on the producer who is unwilling to euthanize sick pigs. PMID- 11195530 TI - [Migraine: dynamics of psychophysiologic pattern]. AB - 85 patients with migraine without aura and 20 healthy individuals were examined between the attacks, before the attack, during and after it (1-2 days). The examination included clinical-neurological analysis; psychological Spilberger's and Beck's tests, scale of alexithymia and complex algesic questionnaire; recording of the conditional negative wave; determination of nociceptive flexor reflex; recording of trigeminal evoked potentials; spectral analysis of the heart's rhythms; polysomnographic study. Psychophysiologic pattern characteristic for all the patients was established. Psychological and neurophysiological parameters changed synchronously in the periods before the attack, during and after it. Before the migraineous attack a specific pathologic integration increased and presented maximally (the activity of antinociceptive system weakens anxiety increased, tension of catecholaminergic systems grew, hyperactivity in trigeninal sphere elevated, tolerance to the pain decreased). A clear tendency to the reversibility of these changes was observed after an attack. A dynamics revealed in the psychophysiological pattern could serve as a predictor of a migraineous attack and open some perspectives for prophylaxis of the algesic attack. PMID- 11195531 TI - [Psychological factors of chronic pain]. AB - To investigate psychological factors, involved in formation of chronic algesic syndrome, 70 patients (50 women, 20 men, mean age--33.5 years) with panic disorder (PD) were examined. The patients were divided into 3 groups: with PD combined with chronic ache (CA) (26 patients); with PD combined with episodical ache (EA) (19 cases); PD without ache (25 individuals). Algesic phenomena were estimated according to "Algesic anamnesis of life" questionnaire; depression level was estimated according to Back's and Hamilton's Rating tests; the level of reactive and personality anxiety--according to Spilberger's inventory test. Severity of psychopathologic syndromes was estimated according to SCL Rating Scale. It was demonstrated that patients with CA and PD have a more significant role of depression in course of the disease as compared with anxiety; prevalence of functional-neurological symptoms in clinical pattern of PD (atypicalness); high level of somatization and a lot of algesic stresses in their life. Factors that prevent chronization of the ache were the following ones: degree of manifestation and the significance of phobic anxiety in the course of the disease, restricting behavior, atypical PD and less number of pain episodes in life. PMID- 11195532 TI - [A specific form of headache with neuralgia-like manifestations (SUNCT syndrome)]. AB - A recently described SUNCT is a rare head ache syndrome characterized by shortlasting, unilateral, neuralgia-like headache attack with conjunctival injection and tearing; 26 cases of SUNCT-syndrome have been reported in medical literature. The authors observed the described symptoms in 3 cases (among 86 patients with trigeminal paroxysmal manifestations). Clinical features of SUNCT syndrome are presented. In addition, the authors discuss possible etiologic factors and treatment as well as a differential diagnosis of SUNCT-syndrome, from trigeminal neuralgia, cluster headache, chronic paroxysmal hemicrania and combined syndromes. PMID- 11195533 TI - [Aspects of the development in dysphagia and its functional dynamics]. AB - 100 patients (88 women, 12 men) of 16-64 years of age with functional dysphagia were examined. In all the cases the disease develops under the influence of stress in individuals with high anxiety, easy formation of dysthymic, obsessive phobic reactions in the situation of frustration. Functional dysphagia arises most frequently at the age of 20-40 years. 4 stages pass in the course of the disease: a stage of reactive (neurotic) depression; psychosomatic reactions; psychosomatic cycles (mono- and polysomic); psychopathization. Psychopathization manifests pathologic (psychosomatic) development of personality observed usually in long-term course of dysphagia. PMID- 11195534 TI - [Imovan in therapy of sleep disorders in patients with cerebral stroke]. PMID- 11195535 TI - [Organic neuroses as psychosomatic problem]. AB - To study a role of psychogenic and somatogenic factors in the development of organic neuroses, 302 patients were examined: 199 with cardioneurosis and 103 with irritable-bowel syndrome (IBS) with mental and subclinical somatic pathology or without it. Two types of organic neuroses were distinguished: a conversive one -somatized hysteria (psychogenically determined subsyndromal hysterohypochondriac phobic or affective reactions with clear difference of algesic and autonomic disorders from symptoms of the somatic pathology, with polymorphism of the involved organic systems); and autonomic neurosis that is a central link in the structure of psychosomatic correlations, which, on the one hand, was overdone by clinical manifestations of the somatic pathology (mitral prolapse--35%, ventricular extrasystoles--12%, etc. in cardioneurosis, lymphoid hyperplasia of colonic mucosa--100%, dysbiopsis--10%, etc. in IBS); on the other hand, autonomic neurosis is a somatopsychic component of psychopathologic disorders of anxious phobic, affective and hypochondriac sphere (panic disorder--59%, generalized anxiety--15%, anxious depression--18% in cardioneurosis, melancholic or hypochondriac cyclothymic depressions--76%, hypochondriac development--24% in IBS). Psychosomatic correlations were considered in autonomic neurosis in the context of some continuum, where somatic disorders amplified by functional disorders are on the one pole and true mental pathology including somatoautonomic disorders--on the other pole. Recommendations have been formulated on therapy of organic neuroses with anxiolytics, antidepressants and atypical neuroleptics in combination with somatotropic drugs. PMID- 11195536 TI - [Application of phototherapy in children with headache]. AB - The paper presents an analysis of the influence of 10 sessions of phototherapy (exposure to bright white light, 3300 lux) in 9 children with episodic headache of tension (EHAT), in 21 children with chronic headache of tension (CHAT) and in 10 children with migraine. Clinical complaints, mood, autonomic status, blood levels of thyroid hormones, hydrocortisone, prolactin, excretion of catecholamines with daily urine were analysed. A course of phototherapy resulted in improvement of the mood, a decrease in the number of the complaints, a tendency to normalization of autonomic homeostasis, an increase in the levels of hydrocortisone and prolactin, a decrease of the high initial level of urine adrenaline and noradrenaline as well as elevation of initially low one in 92.5% of children from all the groups. The most pronounced positive effect was observed after phototherapy in children with CHAT, weaker effect was found in children with migraine. The conclusion is made about optimizing and modulating influence of phototherapy on the levels of stress-realizing hormones and autonomic homeostasis, that improves adaptation of a child's organism. PMID- 11195537 TI - [The influence of alpha-dihydroergocryptine derivatives on psychomotor manifestations in Parkinson disease]. AB - The paper presents the results of administration of alpha-dihydroergocryptine preparation (vasobral) to parkinsonic patients. It was prescribed to 20 patients with parkinsonism together with the specific therapy. Clinical state as well as the level of anxiety and depression was estimated using standard scales both before and after treatment. A high efficiency of vasobral was found as regards such symptoms as disorders of memory, headache, vertigo, a noise in ears and head, asthenic state. In some patients functional activity increased, in 4 patients a dose of dopaminergic preparations was successfully decreased by 25%. An important aspect of vasobral activity was also a decrease of anxious depressive symptoms. A conclusion was made about efficiency of vasobral in combined treatment of parkinsonic patients. PMID- 11195538 TI - [Efficiency of new forms of madopar in Parkinson's disease]. AB - The paper presents estimation of the efficiency of some new forms of madopar (madopar dispergative--Mad-Dis, Mad-HBS) in 26 patients with Parkinson's disease by methods of motor potential, autonomic tests. A good tolerance of Mad-HBS was found. Its administration neither causes changes of autonomic indices nor aggravates symptomatology of cardiovascular disease. A single dose of Mad-Dis may serve as a predictor for a positive result of DOPA-containing preparations in a certain group of patients with Parkinson's disease. PMID- 11195539 TI - [Disorder of eating behavior and comorbid syndromes in obesity and methods of their correction]. AB - Eating behavior and comorbid syndromes were investigated in 40 women with obesity. A frequent combination of obesity with disorders of eating behavior, with emotional-personality, psychoautonomic and algesic disorders as well as with appearance of affective disorders during dietetic nutrition ("dietetic depression") required their correction. As a result of insufficiency of serotoninergic system of brain in pathogenesis of such disorders, fluoxetine (prozac)-a selective inhibitor of serotonine reuptake--was used for treatment of eating disorders. Heterogeneity in the structure of the obesity is shown. Disorders of eating behavior were combined with pronounced anxiety, depression, algesic and psychoautonomic syndromes. Therapy with prozac during 3 months in dose of 20 mg daily resulted in decrease of weight. Normalization of eating pattern, decrease of anxiety, depression, reaction to the external stimuli, increase of stress-resistance of patients, alterations in eating liking, decrease of severity of disorders comorbid to obesity were observed. A conclusion is made that prozac is indicated for patients in whom pathology of eating behavior plays a significant role in pathogenesis of obesity. PMID- 11195540 TI - [The possibility of the use of several clinical, genetic and MRI characteristics for the prognosis of effects of beta-interferon-1beta treatment in multiple sclerosis]. AB - Recently, beta-interferons have become the first line medicine of pathogenic treatment of multiple sclerosis (MS). 75 MS patients from Moscow received the treatment with beta-interferon-1b (betaferon). Clinical, genetic and MRI data on 48 of them were included in detailed statistical analyses. High basic frequency of relapses, absence of atrophy of the brain at the first MRI scans and the presence of HLA-DRB1*15 (less significant DRB1*0301 and DRB1*04) were associated with better clinical effects of one year Betaferon course--decrease of relapses frequency and delay in EDSS progression. PMID- 11195541 TI - [Botox in combined treatment of cerebral palsy in children]. AB - Ten patients with cerebral palsy (CP) were treated with botox (botulinum toxin, type A). The next forms of the disease were observed in the patients: a spastic dysplegia, a spastic hemiplegia, a spastic-hyperkinetic form of CP. Botox was injected into the damaged muscles in a dose of 100-300 Units. Therapeutical effect was found in 90% of the patients, an average duration of the medical effect was 6-12 months. Because of the small cohort of the patients treated with botox there was made a preliminary conclusion about the high efficiency and safety of botox for CP treatment. The need of further clinical observations was emphasized. PMID- 11195542 TI - [Fluvoxamine (fevarin) in the treatment of depression]. AB - 30 patients of 23-73 years old with endogenic and reactive depressions were treated with fevarin. The clinical state of the patients was estimated by means of Hamilton Depression Rating Scale (Ham-D). Fevarin was administrated in daily dose of 100-300 mg; the course of the treatment was equal to 4-8 weeks. The anxiolytic and antidepressive effects of fevarin were developed from the 5-7 days of the therapy: an anxiety disappeared completely by the end of the 3-d week. The most pronounced antidepressive effect was found for the classic depression with melancholy. A mild simulative effect and a normalization of a sleep were also observed. An improvement of the mental state was found in the all the patients by the end of the treatment: in 60% it was significant (a complete remission); in 40%--a considerable improvement was observed with the reduction of all clinical components of the depressive state. Fluvoxamine was found to be the high effective preparation for both endogenic and reactive depressions. PMID- 11195543 TI - [Relative drug resistance as a result of an erroneous approach to patient care]. PMID- 11195544 TI - [Peculiar lexicon in hysteria]. AB - A psycholinguistic association experiment was used to examine 19 hysterical patients with different functional-neurological motor disorders, such as unilateral or bilateral pseudopareses, pseudoataxia and 9 healthy individuals (a control group). The method included three tests: a free associative experiment and different types of the directed associative experiment (grammatically mediated or semantically mediated). According to these tests verbal activity was significantly decreased in the patients as compared with controls and patients with left-sided pseudoparesis as compared with the right-sided one. In addition, there were correlations of verbal activity with the degree of paresis (a positive correlation) and with the level of demonstrability of personality (a negative one). PMID- 11195545 TI - [The use of the instrument for the control of statistic hypotheses for the analysis of patient population in mental hospitals]. AB - To reveal homogeneous groups of old-age patients in psychiatric hospitals, a classic method of mathematical statistics chi 2 criterion of Pearson for the contingency tables was used. The general sample of patients (655 individuals) was from hospitals of Moscow (281 persons), Tver (250 individuals) and Kalyazin (124 patients). Description of the patients was made by means of sets including 44 signs from three blocks: demographic, social and clinical. The pattern of homogeneous and heterogeneous groups was presented for each separate sign that was quite important for practical activity of psychiatrists-gerontologists. PMID- 11195546 TI - [The systemic analysis of the predictors of clinico-social prognosis in schizotypic pseudoneurotic disorder]. AB - By means of the systemic analytic approach (a correlation-regression analysis) author estimated prognostic significance of clinical characteristics of premorbid, initial period and manifestations of schizotypic pseudoneurotic disorders in terms of the level of social adaptation. 232 patients were observed after the fist hospitalization during 10 years. Criteria of both favorable and unfavorable prognosis of the disease were determined. The best prognosis took place in 7.6% of the patients, moderate--in 53.4% and the worst (maladaptation)- in 38.8% of the cases. A favorable prognosis correlated with poorly differentiated (nonspecific for endogenic diseases) disorders and with lack of personal changes. Meanwhile, an unfavorable prognosis correlated with disorders typical for slow-progredient schizophrenia (polymorphic neurosis-like and affective disorders, deficient changes of the personality and cognitive disorders). PMID- 11195547 TI - [Family form of hemiplegic migraine]. PMID- 11195548 TI - [Antiphospholipid syndrome with choreic manifestations]. PMID- 11195549 TI - [Family cases of syringomyelia and Arnold-Chiari anomalies]. PMID- 11195550 TI - Diatheses and stressors in borderline pathology of childhood: the role of neuropsychological risk and trauma. AB - OBJECTIVE: To determine the relative contributions of neuropsychological deficits and psychosocial stressors to the presence of borderline pathology in children. METHOD: The subjects were 86 school-age children (75 males, 11 females) referred for psychiatric day treatment. Thirty-five of the children met criteria for borderline pathology. Data on psychosocial risk factors were obtained for each child from a questionnaire completed by members of the child's clinical team and were based on interviews with parents and children, as well as reports from schools and social agencies. Neuropsychological measures included computerized versions of the Wisconsin Card Sorting Test and the Continuous Performance Test. RESULTS: Both deficits in executive function and psychological trauma made significant and independent contributions to the variance in borderline pathology. Inclusion of both sets of risk factors produced a model that explained 48% of the variance in borderline diagnosis. CONCLUSIONS: Both environmental risks and neurobiological vulnerability should be taken into account to understand the etiology of borderline pathology in children. PMID- 11195551 TI - Latent class analysis of child behavior checklist anxiety/depression in children and adolescents. AB - OBJECTIVE: Comorbidity of psychiatric problems such as anxiety and depression poses challenges to treatment and research. This study tested whether problem items from the Anxious/Depressed scale of the Child Behavior Checklist (CBCL) can be separated into distinct anxiety and depression classes or are continuously distributed throughout a population. METHOD: A CBCL was completed by a parent or guardian of each of 1,987 children and adolescents selected to represent nonreferred children in the United States, as well as by a parent or guardian of each of a demographically matched sample of 1,987 clinically referred children and adolescents. Problem items from the Anxious/Depressed scale of the CBCL were subjected to latent class analysis. RESULTS: Analyses revealed three levels of problem presentation in both samples. Children in the nonreferred sample were classified as having no problems, mild problems, or moderate anxiety/depression problems. Children and adolescents in the referred group were classified as having mild, moderate, or severe levels of problems. No pure anxiety or depression classes were found, only classes containing a mixture of both anxiety and depressive problems. Age, gender, and sample differences were found in class groupings, with nonreferred adolescent girls showing elevated levels of problems. CONCLUSIONS: Results suggest that the comorbid conditions of anxiety and depression, as assessed by the CBCL anxiety/depression problem items, can be thought of as part of the same continuum of problems. Implications for assessment and treatment utilization are discussed. PMID- 11195552 TI - When is an assessment an intervention? Parent perception of infant intentionality and language. AB - OBJECTIVE: To determine whether the process of having parents rate their infant's intentionality and language using parent-report questionnaires influences parents' tendency to view infants as intentional or linguistic. METHOD: The Infant Intentionality Questionnaire (IIQ) and the MacArthur Communicative Development Inventories (CDI) were administered to three groups of mothers. Forty mothers completed the interviews longitudinally when their infants were 8, 10 and 12 months old. A group of 20 mothers completed the interviews longitudinally when their infants were 10 and 12 months old. A third group of 20 mothers completed the interviews at 12 months only. RESULTS: IIQ scores increased across age but also were higher if parents had more experience with the questionnaire. CDI scores increased with age, but there was no effect of repeated testing. CONCLUSIONS: Previous experience with the IIQ seems to have enhanced the tendency to perceive intentionality. In contrast, repeated testing with the CDI did not alter parent perception of child language. These results suggest that some parent report instruments (e.g., the IIQ) can alter the test-taker's awareness and thus could serve as an intervention. Parent-report instruments that tap something that is salient, familiar, and easily observable (e.g., the child's language) are less likely to alter the parent's perception. PMID- 11195553 TI - A therapeutic approach to children and adolescents with anxiety disorders and associated comorbid conditions. PMID- 11195554 TI - Genetics of childhood disorders: XXII. ADHD, Part 6: The dopamine D4 receptor gene. PMID- 11195555 TI - Maternal depression and comorbidity: predicting early parenting, attachment security, and toddler social-emotional problems and competencies. AB - OBJECTIVE: To examine relations between maternal depression (in pure and comorbid forms) and mother-infant interactions, infant attachment, and toddler social emotional problems and competencies. A second objective was to explore sex differences. METHOD: Sixty-nine mother-infant dyads were followed from pregnancy to 30 months postpartum. Depression was measured at multiple times with self report and interview assessments. Play was assessed at 4 months and attachment status at 14 months postpartum. At 30 months, mothers completed the Child Behavior Checklist and Infant-Toddler Social and Emotional Assessment. RESULTS: Lifetime maternal depression predicted less optimal mother-infant interactions and insecure infant attachment. However, this "depression effect" was accounted for by mothers with comorbid diagnoses, who had less optimal interactions, and infants with higher rates of insecurity than either mothers with depression only or mothers with no psychopathology. Prenatal and postpartum depressive symptoms were associated with problem behaviors and lower competencies for boys. In contrast, quality of early interactions predicted problem behaviors in girls. CONCLUSIONS: It is important to examine the context of maternal depression with respect to additional psychopathology and environmental risks. Maternal depression in the presence of other psychopathology confers risk to the mother child dyad. Consistent with previous work, risk pathways appear to differ for boys and girls. Early identification and prevention efforts are warranted. PMID- 11195556 TI - Victimization of children. PMID- 11195557 TI - Effectiveness of mental health services. PMID- 11195558 TI - Diagnoses and interactive patterns of infants referred to a community-based infant mental health clinic. AB - OBJECTIVES: To describe the distribution of symptoms and diagnoses in a community based infant mental health clinic and to compare play and feeding interactions of referred and nonreferred infants. METHOD: The Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood (DC 0-3) was used to diagnose 113 referred infants (60% were boys). Thirty additional dyads were matched with 30 nonreferred dyads. Feeding, play interactions, and home environment were compared. RESULTS: Two peaks of referral were found: 0 to 6 and 12 to 18 months. The main reasons for referral were eating problems, sleep problems, aggressive behavior, irritability, and maternal depression. The most common DC 0-3 diagnosis was a combination of primary infant disorder, parent child relationship disorder, and parental psychopathology. Mothers of referred children provided lower levels of sensitivity, support, and structuring of the interaction, and less optimal home environment. The dyadic relationship showed a lower degree of mutuality and higher negative exchanges. Feeding interactions elicited more negative interactions than play. CONCLUSIONS: Infants referred by community health workers showed less optimal mother-infant interactions and had less optimal environment, compared with nonreferred dyads. Symptoms of emotional distress in infancy are best apprehended when assessed in multi-institutional contexts and formulated in a multiaxial approach. PMID- 11195559 TI - Infant and toddler pathways leading to early externalizing disorders. AB - OBJECTIVE: To examine pathways leading to specific types of early externalizing disorders. METHOD: Longitudinal data were collected on 310 low-income, male subjects followed from infancy until age 6 years. RESULTS: Support across informants was found for the importance of the caregiving environment during infancy in relation to the development of externalizing disorders at school entry. Support was also found for the significance of early child factors, but this was limited to child behavior at home. CONCLUSIONS: The results are consistent with social learning and attachment models, which suggest that severe conduct problems in early childhood are the result of deficits in the caregiving environment. Support was also found for Moffitt's hypothesis that children with the comorbid attention-deficit/hyperactivity disorder-oppositional defiant disorder/conduct disorder pattern experience multiple child and psychosocial risk factors that begin during infancy. PMID- 11195560 TI - Factitious disorder by proxy. PMID- 11195561 TI - Disruptive behavior in young children: what does it mean? AB - OBJECTIVE: To examine how the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood (DC 0-3) primary diagnoses, Parent-Infant Relationship Global Assessment Scale, and Child Behavior Checklist/2-3 (CBCL/2-3) externalizing and internalizing symptoms augment the DSM III-R/IV and guide treatment. METHOD: 82 children aged 18 to 47 months, who presented with disruptive behavior to an early childhood psychiatry clinic, were diagnosed using DSM-III-R/IV, DC 0-3, and the CBCL/2-3. RESULTS: Children with DSM-III-R/IV disruptive disorders or attention-deficit/hyperactivity disorder were diagnosed with DC 0-3 regulatory disorders, disorders of affect, and traumatic stress disorder. Clinically significant externalizing and internalizing symptoms co-presented in 45.1% of the children. Of children with disorders of affect, 41.2% had relationships categorized as disordered, contrasting with 21.1% of those with traumatic stress disorder and 10.3% of those with regulatory disorders. Increasingly disordered relationships were significantly correlated with externalizing and internalizing symptoms, and children with disordered relationships were 3.6 times more likely to have clinically significant levels of internalizing symptoms. CONCLUSION: In these children with disruptive behaviors, co-presentation of externalizing and internalizing symptoms is most common. Those with increased relational risk had more externalizing and internalizing symptoms and more disorders of affect. PMID- 11195562 TI - Paxil and self-scratching. PMID- 11195563 TI - Toward establishing procedural, criterion, and discriminant validity for PTSD in early childhood. AB - OBJECTIVE: To explore several key aspects of the diagnosis and assessment for posttraumatic stress disorder (PTSD) in infants and young children. METHOD: Fifteen traumatized, clinic-referred children, and a comparison sample of 12 at risk children, all younger than 48 months of age, were assessed with a standardized procedure and a semistructured diagnostic interview. The assessments were videotaped and reviewed by two blind raters for scoring DSM-IV PTSD criteria and an alternative set of PTSD criteria for young children. Raters were debriefed and consensus ratings were used to make best-estimate diagnoses. RESULTS: The investigation of procedural validity showed that 12% of the diagnostic criteria present in these children could be detected by a clinician through direct observation or interaction with the children. The remainder of criteria were apparent only through caregiver report. Problematic aspects of parental reporting were most evident for the avoidance/numbing of responsiveness criteria. The traumatized subjects showed significantly more alternative criteria of PTSD than DSM-IV criteria of PTSD. The main sources of rater disagreement are described. CONCLUSIONS: Additional sources of information would complement the multidimensional assessment of PTSD in young children. The set of alternative criteria appears to show greater criterion validity than the DSM-IV criteria. PMID- 11195564 TI - Pineal germinoma and psychosis. PMID- 11195565 TI - Classification of young children's sleep problems: a pilot study. AB - OBJECTIVES: This study examines videotaped sleep in infancy in an attempt to predict the development of disturbed sleep during toddlerhood. In addition, a tentative classification scheme that quantifies night waking and sleep onset problems in young children is proposed. METHOD: The sleep patterns of 33 children were assessed at two points in time. At 12 months of age (time 1), sleep was videotaped on two consecutive nights. A self-soothing/signaling index for 12 month-olds was constructed. At time 2 (mean age = 39 months), a follow-up telephone interview assessed current sleep patterns and the presence or absence of sleep problems. RESULTS: The data suggest that the self-soothing/signaling index obtained at 12 months of age predicts night waking approximately 2 years later. CONCLUSIONS: The preliminary classification scheme for night waking and sleep onset problems in young children warrants further study. Night waking in toddlers might be predictable from sleep behaviors at 1 year of age. PMID- 11195566 TI - Temperamental contributions to social behavior: the moderating roles of frontal EEG asymmetry and gender. AB - OBJECTIVES: Infant temperament is thought to provide one of the fundamental bases for social and emotional development. Few studies have examined the direct and indirect influences of early temperament and physiological disposition on later development. METHOD: This article presents results of a longitudinal study that took place between the years 1989 and 1996 in which the relations between maternal reports of negative reactivity at 9 months of age and maternal ratings and laboratory observations of social wariness and sociability at 4 years of age (n = 97) were examined. Also examined were the moderating roles of (1) frontal electroencephalogram (EEG) asymmetry as assessed at 9 months of age and (2) the child's gender. RESULTS: Negative reactivity predicted social wariness for infants with right frontal EEG asymmetry, but not for those with left frontal EEG asymmetry and for boys but not girls. The only significant predictor of sociability was gender. Specifically, at 4 years of age girls were rated higher on the measure of sociability than were boys. CONCLUSION: The findings are discussed in terms of the roles of frontal EEG asymmetry and gender in moderating the impact of temperamental negative reactivity on later social behavior. PMID- 11195567 TI - Fourteen-year follow-up of speech/language-impaired and control children: psychiatric outcome. AB - OBJECTIVE: To examine the association between early childhood speech and language disorders and young adult psychiatric disorders. METHOD: In a longitudinal community study conducted in the Ottawa-Carleton region of Ontario, Canada, interviewers administered structured psychiatric interviews to age 19 participants who were originally identified as speech-impaired only, language impaired, or nonimpaired at age 5. The first stage of the study took place in 1982 when participants were 5 years old, and the latest stage of the study took place between 1995 and 1997 when participants had a mean age of 19 years. This report examines the association between early childhood speech/language status and young adult psychiatric outcome. RESULTS: Children with early language impairment had significantly higher rates of anxiety disorder in young adulthood compared with nonimpaired children. The majority of participants with anxiety disorders had a diagnosis of social phobia. Trends were found toward associations between language impairment and overall and antisocial personality disorder rates. Males from the language-impaired group had significantly higher rates of antisocial personality disorder compared with males from the control group. Age of onset and comorbidity did not differ by speech/language status. The majority of participants with a disorder had more than one. CONCLUSIONS: Results support the association between early childhood speech and language functioning and young adult psychiatric disorder over a 14-year period. This association underscores the importance of effective and early interventions. PMID- 11195568 TI - Introduction--Assessment of infant and toddler mental health: advances and challenges. PMID- 11195569 TI - Natural course of alcohol use disorders from adolescence to young adulthood. AB - OBJECTIVES: To examine the course of alcohol use disorder (AUD) and determine the extent to which AUD in adolescence is a risk factor for AUD and other psychopathology in young adulthood. METHOD: Nine hundred forty participants from a large community sample in western Oregon were interviewed twice during adolescence (14-18 years of age the first assessment; between 1987 and 1991) and once at age 24 (1993-1999). Between 1995 and 1998, parents were assessed for lifetime AUD. Participants were classified into nonproblematic use (NON), problem drinker (PROB) (symptoms of AUD but no diagnosis), and AUD groups. RESULTS: Adolescent AUD significantly predicted AUD, substance use disorder, depression, and elevated levels of antisocial and borderline personality disorder symptoms by age 24. Compared with the NON group, adolescents in the PROB group were at increased risk for AUD, substance use disorder, depression, and antisocial personality disorder symptoms. However, the PROB group had lower rates of future AUD and antisocial personality disorder symptoms than the adolescent AUD group. Gender interactions were nonsignificant. Daily smoking and conduct/oppositional defiant disorders predicted future AUD, when adolescent AUD and other disorders were controlled. Paternal, but not maternal, AUD was associated with greater risk of future AUD. CONCLUSIONS: For the majority of adolescents, AUD are not benign conditions that resolve over time. Assessment, treatment, and prevention recommendations are discussed. PMID- 11195570 TI - Cognitive risk factors and suicide attempts among formerly hospitalized adolescents: a prospective naturalistic study. AB - OBJECTIVE: To examine the relationship between cognitive variables and time until suicide attempts among 180 adolescents who were monitored for as much as 6.9 years after discharge from an inpatient psychiatry unit. METHOD: In a prospective naturalistic study, adolescents were assessed at the time of their psychiatric hospitalization and semiannually thereafter. Suicidal behavior at index hospitalization and over the follow-up period was assessed with semistructured psychiatric diagnostic interviews. At hospitalization, cognitive risk factors were assessed with a problem-solving task and with questionnaires assessing hopelessness, expectations for posthospitalization suicidal behavior, reasons for living, and dysfunctional attitudes. RESULTS: Expectations about future suicidal behavior were related to posthospitalization suicide attempts. Among youths with previous suicide attempts, higher levels of hopelessness were associated with increased risk, and greater survival and coping beliefs were associated with decreased risk for posthospitalization suicide attempts. Hopelessness and survival and coping beliefs were not related to posthospitalization attempts among adolescents without prior suicidal behavior, and hopelessness was not predictive after controlling for overall severity of depression. CONCLUSIONS: Expectations for suicidal behavior, hopelessness, and survival and coping beliefs provide important prognostic information about later suicidal behavior and should be targeted in interventions with suicidal youths. PMID- 11195571 TI - [Use of data from DNA-DNA hybridization and analysis of 16S rRNA genes for resolving taxonometric problems using the order Haloanaerobiales as an example]. AB - In this review, the validity of evolutionary conclusions inferred from the quantitative estimates of the similarity between bacterial genes is evaluated using the order Halonanaerobiales as an example. The haloanaerobic phenotype is briefly characterized, as are some specific features that allow the order Haloanaerobiales to serve as a reference taxon. Phylogenetic analysis provides a set of standard quantitative criteria for ranking bacterial taxa, from species to families. Recommendations for the use of these standard criteria are given. PMID- 11195572 TI - [Organization and regulation of polyhydroxybutyrate/valerate biosynthesis in bacteria]. AB - Recent data on the biosynthesis of poly(3-hydroxybutyrate) (PHB) and poly(3 hydroxybutyrate-co-3-hydroxyvalerate) (PHB/V) and its regulation in bacteria are reviewed, with special emphasis on the properties and regulation of the relevant enzymes and their genes. Some conditions promoting the synthesis of PHB and PHB/V by natural, mutant, and recombinant producers are considered. PMID- 11195573 TI - [Facultative and obligate aerobic methylobacteria synthesize cytokinins]. AB - The presence and expression of genes controlling the synthesis and secretion of cytokinins by the pink-pigmented facultative methylotroph Methylobacterium mesophilicum VKM B-2143 with the serine pathway and nonpigmented obligate methylotroph Methylovorus mays VKM B-2221 with the ribulose monophosphate pathway of C1 metabolism were shown using the polymerase chain reaction (PCR) and reverse transcription-PCR methods. The presence of the corresponding mRNA in M. mesophilicum cells grown on methanol or succinate suggests that the expression of these genes is constitutive. The cytokinin activity of culture liquid and its fractions was determined by a biotest with Amarantus caudatus L. seedlings. Using enzyme-linked immunosorbent analysis, we detected zeatin (riboside) in the culture liquid of both bacteria studied. The data obtained show that the aerobic methylobacteria are phytosymbionts that are able to utilize the single- and polycarbon compounds secreted by symbiotic plants and to synthesize cytokinins. PMID- 11195574 TI - [Use of poly-beta-oxybutyric acid by Yersinia pseudotuberculosis and Listeria monocytegenes bacteria at various temperatures]. AB - A comparative investigation of the intracellular content of poly-beta hydroxybutyric acid showed that Yersinia pseudotuberculosis strains accumulated, on the average, lower amounts of this reserve substance than Listeria monocytogenes strains. The intracellular pool of poly-beta-hydroxybutyric acid was responsible for the growth of the bacteria at low temperatures (4-6 degrees C) in the absence of any exogenous carbon and energy source. PMID- 11195575 TI - [Production of proteinases associated with Bifidobacterium adolescentis 94-BIM cell wall]. AB - Bifidobacterium adolescentis 94-BIM was found to produce cell-wall bound proteolytic enzymes active at acidic, neutral, and alkaline pH values. The solubilization of proteinases with 0.5% Triton X-100 substantially improved the yield of the enzymes. The most active accumulation of cell-bound proteinases was observed in the third hour of cultivation at rates of 156.7, 179.5, and 111.1 U/(mg h), measured at pH 2.5, 7.0, and 9.0, respectively. It is suggested that the cell-wall bound proteinases of B. adolescentis 94-BIM are the precursors of the enzymes secreted into the medium. PMID- 11195576 TI - [Biosynthesis of Proteus mirabilis nuclease]. AB - The culture liquid and periplasm of Proteus mirabilis contained nuclease, an enzyme with DNase and RNase activities. The nuclease was most actively synthesized in the early exponential and stationary growth phases. Nuclease synthesis was regulated by nucleic acids (induction by substrate) and inorganic phosphate (end-product inhibition). The synthesis and secretion of nuclease by P. mirabilis was induced by mitomycin C, an inducer of the SOS functions of cells. This suggests the involvement of SOS-response proteins in the regulation of nuclease synthesis. PMID- 11195577 TI - [Degradation of phenanthrene by mutant strains--naphthalene degraders]. AB - Five naphthalene- and salicylate-utilizing Pseudomonas putida strains cultivated for a long time on phenanthrene produced mutants capable of growing on this substrate and 1-hydroxy-2-naphthoate as the sole sources of carbon and energy. The mutants catabolize phenanthrene with the formation of 1-hydroxy-2-naphthoate, 2-hydroxy-1-naphthoate, salicylate, and catechol. The latter products are further metabolized by the meta- and ortho-cleavage pathways. In all five mutants, naphthalene and phenanthrene are utilized with the involvement of plasmid-borne genes. The acquired ability of naphthalene-degrading strains to grow on phenanthrene is explained by the fact that the inducible character of the synthesis of naphthalene dioxygenase, the key enzyme of naphthalene and phenanthrene degradation, becomes constitutive. PMID- 11195578 TI - [Composition of lipids from yeast-like and mycelial cells of the fungus Mucor hiemalis, grown in the presence of 4-chloroaniline]. AB - The fungus Mucor hiemalis, which is commonly thought to be monomorphic, produced two types of cells, yeastlike and mycelial, during growth in a medium containing 4-chloroaniline. Among the polar lipids of yeastlike cells, diphosphatidylglycerol was dominant, while phosphatidylcholine and phosphatidylethanolamine were present in minor amounts. Conversely, mycelial cells mainly contained phosphatidylcholine and phosphatidylethanolamine, whereas the content of diphosphatidylglycerol was low. The neutral lipids of yeastlike cells were dominated by diacylglycerides, sterols, and fatty acids. The content of triacylglycerides and sterol esters was low. Yeastlike cells contained higher amounts of saturated fatty acids and lower amounts of unsaturated fatty acids than the mycelium. The content of stearic acid in the fatty acids of the mycelium grown in the presence of 4-chloroaniline was as high as 25.3-29.9%. PMID- 11195579 TI - [Characterization of a new strain of Bacillus thuringiensis, a producer of an endotoxin against coleoptera]. AB - A new strain of Bacillus thuringiensis 2-7 was found to belong to the serotype H8. Cells of this strain contained irregular and flat crystalline inclusions and two large plasmids. The gene responsible for crystal formation is most likely located on the large plasmid greater than 105 MDa in size. Comparison of the cry gene of B. thuringiensis 2-7 and the cryIIIA gene of B. thuringiensis subsp. tenebrionis showed that their nucleotide sequences are identical. PMID- 11195580 TI - [A new species of psychrophilic basidiomycetes yeast Leucosporidium fasciculatum sp. Nov]. AB - A psychrophilic yeast with a basidiomycetous developmental cycle and properties corresponding to the genus Leucosporidium Fell et al. was isolated from the fruiting body of the edible spring mushroom Gyromitra esculenta Pers. picked near Moscow. However, the isolate differed from all Leucosporidium species described to date in a number of characteristics. The results of the study of the developmental cycle and of the cultural, morphological, physiological, and biochemical properties of the new isolate, strain KBP Y-3696, allow it to be assigned to a new species of the genus Leucosporidium. PMID- 11195581 TI - [Growth of Escherichia coli cell culture and frequency of mutation, induced by N methyl-N'-nitro-N-nitrosoguanidine]. AB - The rate of Escherichia coli mutation with N-methyl-N'-nitro-N-nitrosoguanidine was found to depend on the age of the culture and the pH value of the incubation medium. The mutability of late-logarithmic cells was higher than that of mid logarithmic cells. Rifampicin, a transcription inhibitor, enhanced the mutagenic action of MNNG on cells from the late logarithmic and early stationary phases suspended in a medium with a pH of 7.4, and on cells from the mid-logarithmic phase suspended in a medium with a pH of 6.5. Conversely, streptomycin decreased the frequency of induced mutations in cells from the late logarithmic and early stationary phases suspended in the medium with a pH of 7.4, and in cells from the mid-logarithmic and early stationary phases suspended in the medium with a pH of 6.5. These data were interpreted as showing that the repair of premutational DNA lesions induced by MNNG depends on the level of DNA transcription and translation. PMID- 11195582 TI - [Assimilation of carbon dioxide and oxidation of methane in various zones of the Rainbow hyperthermophilic field zones]. AB - Rates of carbon dioxide assimilation and methane oxidation were determined in various zones of the Rainbow Hydrothermal Field (36 degrees N) of the Mid Atlantic Ridge. In the plume above the hydrothermal field, anomalously high methane content was recorded; the microbial population density (up to 10(5) cells/ml) was an order of magnitude higher than the background values; and the CO2 assimilation rate varied from 0.01 to 1.1 micrograms C/(1 day). Based on the data on CO2 assimilation, the production of organic carbon due to bacterial chemosynthesis in the plume was calculated to be 930 kg/day or 340 tons/year (about 29% of the organic carbon production in the photic zone). In the black smoke above active smokers, the microbial population density was as high as 10(6) cells/ml; the rate of CO2 assimilation made up 5-10 micrograms C/(1 day); the methane oxidation rate varied from 0.15 to 12.7 mu/(1 day); and the methane concentration ranged from 1.05 to 70.6 mu/l. In bottom sediments enriched with sulfides, the rate of CO2 assimilation was at least an order of magnitude higher than in oxidized metal-bearing sediments. At the base of an active construction site, whitish sediment was found, which was characterized by a methane high content (92 mu/dm3) and a high rate of oxidation (1.7 mu/(dm3 day)). PMID- 11195583 TI - [Microbiological study of the northern part of the Barentz Sea at the onset of winter]. AB - The total number of microorganisms and rates of microbial processes of the carbon cycle were determined in snow, sea ice, water, and seafloor sediments of the northern part of the Barents Sea from September to October, 1998. The explorations were carried out in two areas: along the trajectory from Franz Josef Land to Victoria Island and along the continental slope region covered with solid ice at latitude 81 degrees-82 degrees N and longitude 37 degrees-39 degrees E. At the time of study, the ice cover was represented by thick one-year old ice (up to 1.2 m), perennial ice (up to 1.85 m), and pack ice. The number of bacteria in the snow cover, sea ice, and seawater was 12 to 14, 50 to 110, and 10 to 240 x 10(3) cells/ml, respectively. Rates of CO2-assimilation in the absence of light, glucose utilization, and methane oxidation by bacteria were determined. The highest rate of microbial processes was found in samples of the lowermost newly formed sea ice. The lowest level of activity for all processes was observed from melted snow water. A direct relation was shown between the concentration of Corg, the bacterial biomass, and the values of delta 13Corg in mixtures of melted snow and ice. The number of microorganisms and rates of microbial processes in seafloor sediments measured at the stations on the continental slope are comparable to those in the central part of the Barents Sea and the northern part of the Kara Sea. PMID- 11195584 TI - [Microbiological processes of the carbon and sulfur cycle in cold methane seeps in the North Atlantic]. AB - Functioning of microbial communities in surface sediments of the Haakon Mosby underwater mud volcano (lat. 72 degrees N) and in gas seepage fields of the Vestnesa Ridge was investigated using Mir-1 and Mir-2 deep-sea submersibles during the 40th expedition of the research vessel Academician Mstislav Keldysh. Large areas of sedimentary deposits of the Haakon Mosby mud volcano (HMMV) and pockmarks of the Vestnesa Ridge (VR) are covered with bacterial mats 0.1 to 0.5 cm thick. The microbial community making up bacterial mats of the HMMV was predominated by large filamentous bacteria with filaments measuring up to 100 microns in length and 2 to 8 microns in width. The occurrence of rosettes allowed the observed filamentous bacteria to be referred to the morphologically similar genera Leucothrix or Thiothrix. Three morphological types of filamentous bacteria were identified in bacterial mats covering VR pockmarks. Filaments of type one are morphologically similar with representatives of the genera Thioploca or Desmanthos. Type two filaments had numerous inclusions of sulfur and resembled representatives of the genus Thiothrix. The third morphological type was constituted by single filaments made up of tightly connected disk-like cells and can, apparently, be assigned to the genus Beggiatoa. The rates of methane oxidation (up to 1570 microliters C/(dm3 day)) and sulfate reduction (up to 17 mg S/(dm3 day)) measured in surface sediments of HMMV and VR were close to the maximum rates of these processes observed in badly polluted regions of the northwestern shelf of the Black Sea. High rates of microbiological processes correlated with the high number of bacteria. The rate of methane production in sediments studied was notably lower and ranged from 0.1 to 3.5 microliters CH4/(dm3 day). Large areas of the HMMV caldera were populated by pogonophoras, represented by the two species, Sclerolinum sp. and Oligobrachia sp. The mass development of Sclerolinum sp. in the HMMV caldera was by the activity of aerobic methane-oxidizing bacteria localized inside the cells of these animals. Bacterial cells were also found in the trophosome tissue of Oligobrachia sp., but in cells of these bacteria, we did not observe the membrane structures typical of methanotrophs. The localization pattern of pogonophoras on the surface of reduced sediments suggests that the predominant bacteria in Oligobrachia tissues are sulfur-oxidizing endosymbionts. PMID- 11195585 TI - [Effect of sodium salicylate on the population dynamics of a rhizospheric strain of Pseudomonas aureofaciens in soil and on wheat roots]. AB - The effect of sodium salicylate on the population dynamics of the rhizobacterium Pseudomonas aureofaciens BS1393 and its variant bearing the naphthalene biodegradation plasmid pBS216 was studied in the wheat rhizoplane and adjacent soil. Optimum salicylate concentration for the maintenance of the plasmid-bearing strain and for the normal growth of wheat was found to be 250 micrograms/g soil. When the soil was supplemented with salicylate, the population of P. aureofaciens BS1393(pBS216) in the wheat rhizoplane and adjacent soil was, respectively, 4- and 20-fold higher than that of the parent strain lacking the plasmid. PMID- 11195586 TI - [Effect of Trichoderma species fungi on soil micromycetes, causing infectious conifer seedling lodging in Siberian tree nurseries]. AB - Soils in the tree nurseries studied were characterized by a lower species diversity of fungi than adjacent virgin soils. In particular, the relative abundances of representatives of the genera Mucor, Chaetomium, and Trichoderma in the nursery soil were two times lower than in adjacent virgin soils. On the other hand, the nursery soil exhibited greater abundances of fungi of the genus Fusarium, which are causative agents of many diseases of conifer seedlings. To appreciate the efficiency of biocontrol of the infectious diseases of conifer seedlings, we introduced several indigenous Trichoderma strains into the nursery soil and found that this affected the species composition of soil microflora considerably. Changes in the species composition of mycobiota beneficially influenced the phytosanitary state of soils and reduced the infectious lodging of conifer seedlings. PMID- 11195587 TI - [Chromatic adaptation of ancient viable cyanobacteria from Arctic permafrost]. PMID- 11195588 TI - [The phylogenetic position of aerobic, moderately-thermophilic bacteria of the Sulfobacillus species, oxidizing Fe2+, S(0) and sulfide minerals]. PMID- 11195589 TI - [Monoclonal antibodies as an instrument to study fibrin polymerization]. AB - Examples of using monoclonal antibodies (MAb) for studying the fibrin polymerization mechanism are considered. MAb with epitopes situated in the fibrin polymerization sites or in the recognition sites of enzymes thrombin, plasminogen, and factor XIII, which are the functional partners of fibrin, are primarily discussed. The MAb to epitopes in various regions of A alpha, B beta, and gamma polypeptide chains of the functionally important E, D, and alpha C domains of fibrin are successively described. PMID- 11195590 TI - [Phytoecdysteroids: structure, sources and biosynthetic pathways in plants]. AB - Data on the content of ecdysteroids in plant sources are given and the ecdysteroid biosynthesis and role in plants are discussed. PMID- 11195591 TI - [Synthetic peptide designs based on immunoactive fragments of the VP1 protein of the foot-and-mouth disease virus strain A22]. AB - Peptide constructs consisting of 44-53 aa were synthesized on the basis of sequences 135-159, 170-190 and 197-213 of VP1 from the foot-and-mouth disease A22 strain. Immunogenic and protective properties of the peptide constructs were studied in guinea pigs and mice of three lines. The constructs were shown to induce higher levels of antibodies and exhibit higher protective effects than the separate peptides. The most active among the peptides studied was the construct involving the VP1 fragments 135-160 and 170-190: it protected pigs from the experimental infection by the foot-and-mouth disease virus. PMID- 11195592 TI - [The chromosomal genes for black widow spider neurotoxins do not contain introns]. AB - The overlapping fragments of the chromosomal DNA from black widow spider Latrodectus mactans carrying genes for high-molecular-mass protein neurotoxins, alpha- and delta-latroinsectotoxins (alpha-LIT and delta-LIT) and alpha latrotoxin (alpha-LTX), were PCR-amplified and cloned. Restriction analysis of the PCR products showed that the distribution and sizes of the restriction fragments coincided with those deduced from the earlier sequencing of cDNAs of the corresponding genes. It thus followed that the alpha-LIT and delta-LIT genes are intronless. Along with our data on the structure of the alpha latrocrustotoxin (alpha-LCT), this implies that the lack of introns is a common feature of the black widow spider genes encoding high molecular mass neurotoxins. PMID- 11195593 TI - [Oligomerization of DNA-(adenine-N6)-methyltransferase from phage T4 and its effect on the catalytic characteristics of the enzyme]. AB - The structural and catalytic properties of the phage T4 DNA-(adenine-N6) methyltransferase (EC 2.1.1.72) were studied at different enzyme-substrate concentration ratios by chemical cross-linking of the protein subunits and by measuring the presteady state kinetics of the reactions. Various structural states of the methyltransferase were correlated with its catalytic activity, and it was shown that the oligomeric forms of the enzyme are catalytically active but are characterized by the reaction parameters different from those of the monomer. PMID- 11195594 TI - Perspectives. It's lonely in the middle of the road: big story is compromises not agreed to. PMID- 11195595 TI - Bold new Medicaid model encourages DM innovation. PMID- 11195596 TI - Seeking a DM approach to diagnosis, treatment of ADHD in adults. AB - Get a handle on diagnosis and treatment of ADHD in adults. Mental health practitioners are beginning to recognize that adults, too, can have ADHD, but a large percentage of them are falling through the cracks, often with devastating consequences. Further complicating the problem is the fact that there is widespread practice variation in how the disorder is diagnosed and treated. Now some experts are developing standardized assessment tools, and while the science to back up such efforts is admittedly lacking, it is clear that progress is being made. PMID- 11195597 TI - Use your data to efficiently monitor chronic illnesses. AB - Internet-based approach streamlines the work of case managers. Phone based follow up programs can work well in monitoring chronically ill patients, but they are labor intensive. To get around this problem, a Colorado provider has teamed up with an application service provider to automate the collection of important data on a real-time basis. The result is an Internet-based system of alerts which tells case managers who they need to call and when. PMID- 11195598 TI - Web-based 'early warning' predictive modeling system enhances preventive care. AB - Shifting the focus of disease management from treatment to prevention. There is nothing new about the concept of health risk assessment. Most of these tools seek to identify people with chronic disease so that interventions can be employed. But a cadre of DM firms think that approach does not go far enough. See how one firm is trying to move the focus from treatment to prevention of disease in the first place. PMID- 11195599 TI - Diabetes, hypertension, and cardiovascular disease. PMID- 11195600 TI - Significance of circulatory epinephrine levels in exercise-induced neurally mediated syncope. AB - BACKGROUND AND HYPOTHESIS: Previous research has failed to document temporal changes in epinephrine levels in patients with neurally mediated syncope associated with exercise. The purpose of this study was to investigate the role of circulatory catecholamines in exercise-induced neurally mediated syncope, specifically focusing on epinephrine levels. METHODS: The present study deals with temporal changes of circulatory catecholamine levels during head-up tilt tests (40 min, 80 degree tilt) in 62 patients with syncope of unknown origin, 7 of whom had syncope associated with exercise (exercise-induced group, 19+/-3 years). Data were compared with 10 control subjects (control group, 45+/-23 years). Of the 55 patients with syncope not associated with exercise, 32 tested positive for the head-up tilt tests (positive group, 31+/-16 years) and 23 patients tested negative (negative group, 46+/-19 years). Blood samples for circulatory catecholamine assay were obtained from the antecubital vein in the baseline supine position 2 min after the tilt started, every 10 min during tilt, and at the time of the onset of symptoms or the end of tilt. Levels of norepinephrine and epinephrine were determined using the high-pressure liquid chromatography (HPLC) method (pg/ml). RESULTS: Plasma norepinephrine levels among the four groups were similar at the supine position and during tilt testing. In contrast, patients in the exercise-induced group had significantly higher maximum epinephrine levels during head-up tilt testing than the other three groups (288+/ 191 vs. 148+/-117, 66+/-31, and 54+/-27 pg/ml, respectively, p < 0.05). Patients in the positive group had higher maximum epinephrine levels than those in the negative group (p <0.05). Also, patients in the exercise-induced group and those in the positive group had a significantly shorter tilt-testing time than patients in the negative and control groups. CONCLUSIONS: A marked increase of epinephrine was observed during head-up tilt testing in patients with neurally mediated syncope associated with exercise. The present findings further accelerate the identification of the role of epinephrine in the mechanisms behind neurally mediated syncope associated with exercise. PMID- 11195601 TI - Right ventricular involvement in hypertrophic cardiomyopathy: a case report and literature review. AB - Although hypertrophic cardiomyopathy (HCM) is classically considered a disease of the left ventricle, right ventricular (RV) abnormalities have also been reported. However, involvement of the right ventricle in HCM has not been extensively characterized. The literature regarding prevalence, genetics, patterns of involvement, histologic findings, symptoms, diagnosis, and treatment of RV abnormalities in HCM is reviewed. To highlight the salient points, a case is presented of apical HCM with significant RV involvement, with an RV outflow tract gradient and near obliteration of the RV cavity, in the absence of a left intraventricular gradient. Right ventricular involvement in HCM appears to be as heterogeneous as that of the left ventricle. The spectrum extends from mild concentric hypertrophy to more unusual severe, obstructive disease. While in some cases the extent of RV involvement correlates with left ventricular (LV) involvement, predominant RV disease can be seen as well. While the genetics of RV involvement have not been well characterized, histologic findings appear to be similar to those in the left ventricle, suggesting similar pathogenesis. Significant RV involvement may result in RV outflow obstruction and/or reduced RV diastolic filling, with potentially increased incidence of severe dyspnea, supraventricular arrhythmias, and pulmonary thromboembolism. The optimal treatment for patients with significant RV disease is unknown. Medical and surgical therapies have been attempted with variable success; experience with newer techniques such as percutaneous catheter ablation has not been reported. Further characterization of RV involvement in HCM is necessary to elucidate more clearly the clinical features and optimal treatments of this manifestation of HCM. PMID- 11195602 TI - Myocardial viability in patients with thrombolyzed myocardial infarction: is it assessable by predischarge exercise electrocardiography test? AB - BACKGROUND: Most studies concerning exercise electrocardiography (ECG) testing after acute myocardial infarction (AMI) were carried out in the prethrombolytic era. ST-segment elevation in the infarction area during exercise has usually been interpreted as indicating the presence of dyskinesia as a result of extensive left ventricle damage. HYPOTHESIS: This study was undertaken to evaluate the contributions of exercise-induced ST-segment elevation and T-wave pseudonormalization to the assessment of myocardial viability in patients with thrombolyzed myocardial infarction (MI), compared with low-dose dobutamine echocardiography. METHODS: The study comprised 52 consecutive patients with AMI treated with thrombolysis. All patients underwent low-dose dobutamine echocardiography and symptom-limited exercise testing before discharge. RESULTS: Nineteen patients showed ST-segment elevation (Group 1), 9 showed isolated T-wave pseudonormalization (Group 2), and 24 patients did not exhibit either of these ST T segment changes (Group 3). Low-dose dobutamine echocardiography revealed evidence of viability in 16 patients (84%) in Group I (p = 0.01), 5 (56%) in Group 2 (p = NS), and 11 patients (46%) in Group 3 (p = NS). CONCLUSION: Exercise induced ST-segment elevation may contribute to the evaluation of myocardial viability in patients with AMI treated with thrombolysis. However, in the absence of exercise-induced ST-segment elevation, further noninvasive studies might be indicated to assess myocardial viability. PMID- 11195603 TI - Screening for carotid artery disease before cardiac surgery: is current clinical practice evidence based? AB - BACKGROUND: There is no clear consensus as to the correct screening procedure to identify patients undergoing cardiac surgery and who are at greatest risk of stroke because of the presence of significant carotid artery stenosis. Such screening is important because some patients benefit from combined carotid and cardiac surgery and, regardless of this, the information gained puts the cardiac surgeon in a position to provide an accurate assessment of surgical risk. Our objective was to examine current clinical practice of carotid artery investigation prior to urgent cardiac surgery and to review this illustrative practice in the context of the world literature. HYPOTHESIS: The study aimed to establish that current typical practice for screening cardiac surgical patients for carotid artery disease is illogical according to the evidence in the world literature. METHODS: The study consisted of a retrospective assessment of all patients undergoing urgent cardiac surgery and a Medline-derived literature review, and included all patients undergoing urgent cardiac surgery at a tertiary cardiothoracic center between January 1 and December 31, 1997. RESULTS: Of 529 patients undergoing urgent cardiac surgery, 44 (8%) were screened preoperatively by duplex Doppler ultrasonography for carotid disease. The indications for screening were asymptomatic carotid bruit in 24 patients, history of stroke or transient ischemic attack (TIA) in 12 patients, and neither stroke, TIA, or bruit in 7 patients. The tests were requested either by the attending cardiologists or by the cardiac surgeon to whom they were referred. One patient had already been diagnosed as having carotid artery disease in the past. Thirteen patients underwent additional carotid investigations. Eleven patients were demonstrated to have internal carotid artery stenosis > or = 60% and 3 patients underwent combined cardiac and carotid surgery. Review of the literature revealed the following groups to be at increased risk of future stroke unrelated to surgery, and of postoperative stroke: those with a history of stroke or TIA, those with carotid bruits, and, of importance, all patients with significant carotid stenosis. Recent data suggest that symptomatic patients and the elderly are at greatest risk. CONCLUSIONS: Only 8% of patients undergoing urgent cardiac surgery in a 1-year period were screened for carotid artery disease. We suggest that screening should definitely be performed in all patients with a history of stroke or TIA, all patients with a bruit, and all patients aged > 65 years. The literature suggests, however, that significant reductions in stroke rate could be achieved by screening the whole cardiac surgical population, although there is a paucity of data that are specifically pertinent to this patient subgroup. Further data are therefore required for the construction of a scientifically valid and medicolegally sound policy. PMID- 11195604 TI - Electrocardiographic criteria for predicting total occlusion of the proximal left anterior descending coronary artery in anterior wall acute myocardial infarction. AB - BACKGROUND: Patients with occlusion of the left anterior descending coronary artery (LAD) proximal to both the first septal branch and the first diagonal branch may benefit most from early reperfusion therapy due to extensive area at risk. HYPOTHESIS: The aim of the study was to examine whether 12-lead electrocardiograms (ECGs) in the acute phase of acute myocardial infarction (AMI) could identify total occlusion of the LAD proximal to both the first septal and the first diagonal branch. METHODS: A 12-lead electrocardiogram was recorded on admission in 128 patients with anterior AMI within 12 h from symptom onset. Patients were divided into three groups according to the culprit lesion: 33 patients had total occlusion of the LAD proximal to both the first septal perforator and the first diagonal branch (Group P), in 51 it was proximal to either the first septal perforator or the first diagonal branch (Group D-a), and in 44 it was distal to both the first septal perforator and the first diagonal branch (Group D-b). RESULTS: Sensitivity and specificity of a greater degree of ST-segment depression in lead III than that of ST-segment elevation in lead aVL were 85 and 95%, respectively, which was better than the results derived by all other ECG criteria (p< 0.001). CONCLUSIONS: We conclude that a greater degree of ST-segment depression in lead III than that of ST-segment elevation in lead aVL is a useful predictor of proximal LAD occlusion in patients with anterior AMI. PMID- 11195605 TI - Influence of age on left atrial appendage function in patients with nonvalvular atrial fibrillation. AB - BACKGROUND: Age is an independent risk factor for thromboembolism in nonvalvular atrial fibrillation (NVAF). An association between low left atrial appendage (LAA) Doppler velocities and thromboembolic risk in NVAF has been reported. HYPOTHESIS: The study was undertaken to identify age-related differences in LAA function that may explain the higher thromboembolic rates in older patients with NVAF. METHODS: Forty-two consecutive patients (age 69+/-2 years [range 42-92], 24 [57%] men) with NVAF underwent transthoracic and transesophageal echocardiography. The following were compared in 22 patients younger and 20 older than 70 years: left ventricular (LV) diameter, mass and ejection fraction, left atrial (LA) diameter and volume, LAA area and volume, LAA peak emptying (PE) and peak filling (PF) velocities, presence and severity of spontaneous echo contrast (SEC) and mitral regurgitation (MR). RESULTS: Left atrial diameter (4.6+/-0.1 vs. 4.5+/-0.2 cm), LA volume (105+/-10 vs. 92+/-8 ml), LAA area (6.8+/-0.6 vs. 5.2+/ 0.8 cm2), and LAA volume (5.6+/-0.9 vs. 3.9+/-1.0 ml) were similar (p>0.05) in both groups. Older patients had lower LAA PE (26+/-2 vs. 34+/-3 cm/s, p = 0.02) and PF (32+/-2 vs. 41+/-4 cm/s, p = 0.04) velocities, lower LV mass (175+/-13 vs. 234+/-21 gm, p = 0.02), higher relative wall thickness (0.52+/-0.02 vs. 0.43+/ 0.03, p = 0.02), smaller LV diastolic diameter (4.3+/-0.1 vs. 5.2+/-0.2 cm, p < 0.001), and higher LV ejection fraction (62+/-2 vs. 55+/-2%, p = 0.025). Frequency and severity of SEC and MR were similar in both groups. Multivariate analysis identified older age as the only significant predictor of reduced LAA velocities. CONCLUSION: Compared with younger patients, older patients with NVAF have lower LAA velocities despite higher LV ejection fraction, smaller LV size, and similar LA and LAA volumes. These findings may explain the higher thromboembolic rates in older patients with NVAF. PMID- 11195606 TI - Silent ischemic interval on exercise test is a predictor of response to drug therapy: a randomized crossover trial of metoprolol versus diltiazem in stable angina. AB - BACKGROUND AND HYPOTHESIS: There is no method available to predict the relative antianginal efficacy of beta blockers and calcium-channel antagonists. The present study was undertaken to assess the role of silent ischemic interval (SII) on exercise treadmill test (ETT) as a predictor of response to therapy with metoprolol and diltiazem in patients with stable angina. METHODS: Thirty-four patients with stable angina were divided into two groups depending upon the presence or absence of an SII gap of at least 1 min between onset of ST depression and appearance of angina on ETT. Metoprolol (50-100 mg twice daily) and diltiazem (60-120 mg three times daily) were randomly assigned for 6 weeks to patients in each group, and then patients were crossed over for further 6 weeks after a washout period of 2 weeks. Antianginal efficacy was assessed by clinical and exercise parameters. RESULTS: In patients with SII, the clinical responder rate was better with metoprolol than with diltiazem (90 vs. 60%, respectively), and on ETT, metoprolol produced significant improvement in the total exercise time (p< 0.01), time to 1 mm ST depression (p <0.01), time to angina (p <0.01), and a significant decrease in peak rate-pressure product (p<0.001), whereas diltiazem had no significant effect on exercise parameters. However, in patients without SII, metoprolol and diltiazem had a similar clinical responder rate (57%), and both produced a significant increase in total exercise time (p < 0.01), time to 1 mm ST depression (p < 0.01), and time to angina (p < 0.01). In addition, metoprolol had a significant effect on peak rate-pressure product (p < 0.001). CONCLUSION: Silent ischemic interval on ETT can be a predictor of response to antianginal therapy in stable angina, as patients with SII respond better to metoprolol and those without SII respond equally to both metoprolol and diltiazem. PMID- 11195607 TI - Association between calcific aortic stenosis and hypercholesterolemia: is there a need for a randomized controlled trial of cholesterol-lowering therapy? AB - BACKGROUND: Calcific aortic stenosis may have common etiological factors with atherosclerosis. HYPOTHESIS: In this retrospective, case-control study, we aimed to determine whether there is an association between hypercholesterolemia and calcific aortic valve stenosis. METHODS: Consecutive patients undergoing single aortic or mitral valve replacement in a regional cardiothoracic surgical center were reviewed and preoperative patient characteristics were recorded: demographics, comorbidity (including coronary artery disease and associated risk factors), serum total cholesterol, lipid-lowering therapy, and serum creatinine. RESULTS: Serum total cholesterol concentrations were significantly higher in patients with calcific aortic stenosis than in controls (6.2+/-1.1 vs. 5.3+/-1.1 mmol/l; p < 0.001). The significant difference in serum cholesterol concentrations remained following correction for gender and body mass index (p = 0.02) and when patients with coronary artery disease were excluded (6.3+/-1.1 vs. 5.3+/-1.4 mmol/l; p<0.001). Subgroup analysis demonstrated that the association between elevated serum cholesterol concentrations and calcific aortic stenosis was particularly strong in patients with tricuspid aortic valves (6.4+/-1.2 vs. 5.3+/-1.1 mmol/l; p < 0.001) compared with those with bicuspid valves (5.9+/-1.1 vs. 5.3+/-1.1 mmol/l; p = 0.06). CONCLUSIONS: We conclude that hypercholesterolemia is associated with calcific aortic stenosis and may be implicated in its pathogenesis and progression. We believe that there is now a need for a randomized, controlled trial of cholesterol-lowering therapy in patients with calcific aortic stenosis. PMID- 11195608 TI - Length of stay and procedure utilization are the major determinants of hospital charges for heart failure. AB - BACKGROUND: Most of the 10 billion dollars spent annually on heart failure (HF) management in this country is attributed to hospital charges. There are widespread efforts to decrease the costs of treating this disorder, both by preventing hospital admissions and reducing lengths of stay (LOS). HYPOTHESIS: The objective of this study was to identify the major determinants of hospital charges for an acute hospitalization for HF among a large, diverse group of patients. METHODS: Administrative information on all 1995 New York State hospital discharges assigned ICD-9-CM codes indicative of HF in the principal diagnosis position were obtained. Bivariate and multivariate statistical analyses were utilized to determine those patient- and hospital-specific characteristics which had the greatest influence on hospital charges. RESULTS: In all, 43,157 patients were identified. Mean hospital charges were $11,507+/-15,995 and mean hospital LOS was 9.6+/-14.5 days. With multivariate analyses, the most significant independent predictors of higher hospital charges were longer LOS, admission to a teaching hospital, treatment in an intensive care unit, and the utilization of cardiac surgery, permanent pacemakers, and mechanical ventilation. Age, gender, race, comorbidity score, and medical insurance, as well as treatment by a cardiologist and death during the index hospitalization were not among the most significant predictors. CONCLUSIONS: We conclude that LOS and procedure utilization are the major determinants of hospital charges for an acute episode of inpatient HF care. Reducing LOS and other initiatives to restructure hospital based HF care may reduce total health care costs for HF. PMID- 11195609 TI - Combination treatment with telmisartan and hydrochlorothiazide in black patients with mild to moderate hypertension. AB - BACKGROUND: Hydrochlorothiazide (HCTZ) is commonly used to treat black patients with hypertension. To avoid the metabolic disturbances associated with high-dose HCTZ, blood pressure control may be achieved by combining low doses with another antihypertensive. HYPOTHESIS: The study was undertaken to assess the tolerability and antihypertensive dose-response efficacy of telmisartan and HCTZ and their combination in black patients with mild to moderate hypertension (mean supine blood pressure 140/95-200/114 mmHg). METHODS: Following a 4-week, single-blind, placebo run-in period, 222 black patients were randomized to once-daily treatment with one of 20 different double-blind combinations of telmisartan (0, 20, 40, 80, 160 mg) and HCTZ (0, 6.25, 12.5, 25 mg) for 8 weeks. Blood pressure was measured at baseline and after 2, 4, and 8 weeks. RESULTS: Telmisartan 80 mg/HCTZ 12.5 mg reduced supine trough diastolic blood pressure (DBP)--primary efficacy parameter- by 13.3 mmHg, and supine trough systolic blood pressure (SBP) by 21.5 mmHg. These reductions represented benefits of 13.7/8.7 mmHg over telmisartan 80 mg and 12.3/8.1 mmHg over HCTZ 12.5 mg (p < 0.01). Telmisartan 40 mg/HCTZ 12.5 mg reduced supine trough SBP/DBP by 14.3/10.0 mmHg, amounting to 12.3/3.3 mmHg more than telmisartan 40 mg and 5.1/4.8 mmHg more than HCTZ 12.5 mg. This reached significance for the comparisons with telmisartan 40 mg for SBP and HCTZ 12.5 mg for DBP (p<0.05). A response surface analysis and therapeutic response rates confirmed the additive antihypertensive effects of telmisartan and HCTZ. All treatments were well tolerated, with side-effect profiles comparable with placebo. Adverse events were mainly transient and of mild to moderate severity. CONCLUSIONS: Telmisartan 80 mg combined with HCTZ 12.5 mg is effective and well tolerated in black patients with mild to moderate hypertension, providing greater antihypertensive activity than the corresponding monotherapies. PMID- 11195610 TI - Heart rate-lowering and -regulating effects of once-daily sustained-release diltiazem. AB - BACKGROUND: Epidemiologic evidence suggests that an elevated heart rate (HR) is an adverse and independent prognostic factor in arterial hypertension and other cardiovascular diseases. Although diltiazem is characterized as an HR-lowering calcium antagonist, no studies have quantified the magnitude of HR changes in patients with angina or hypertension. HYPOTHESIS: The study was undertaken to explore the magnitude of proportional HR reduction at varying levels of resting HR with the sustained-release formulation of diltiazem (SR diltiazem) at the usual clinical doses of 200 or 300 mg once daily. METHODS: This meta-analysis was conducted on six comparative double-blind studies including 771 patients with angina or hypertension in which SR diltiazem 200-300 mg once daily was compared either with placebo or with other agents known not to influence HR (angiotensin converting enzyme inhibitors, diuretics). Sustained-release diltiazem decreases elevated baseline HR, with an increasing effect at higher initial rates. RESULTS: Multiple comparisons by baseline HR category showed a significant difference between both groups for baseline HR of 74-84 beats/min and > or = 85 beats/min (p = 0.001). Sustained-release diltiazem had no significant HR-decreasing effect on baseline HR < or =74 beats/min but appears to have a genuine regulating effect on HR: it reduces tachycardia without inducing excessive bradycardia. These findings are in contrast to those with dihydropyridine calcium antagonists, which tend to increase HR and have been associated with an adverse outcome in acute cardiovascular conditions. At the same time, there is evidence to suggest that HR lowering calcium-channel blockers decrease cardiovascular event rates following myocardial infarction. CONCLUSION: When calcium antagonists are indicated for use in patients with angina or hypertension, an HR-lowering agent, that is, diltiazem rather than dihydropyridine, should be recommended. PMID- 11195611 TI - Homocysteine: a new cardiac risk factor? AB - Elevated plasma homocysteine levels have recently been implicated as a new risk factor for coronary artery disease. In this article, homocysteine metabolism, secondary causes of elevated plasma homocysteine, and the potential mechanism of vascular damage in hyperhomocysteinemia are briefly reviewed. The current clinical evidence implicating hyperhomocysteinemia as a risk factor for coronary artery disease, as well as the data regarding the effects of B vitamin supplementation on homocysteine concentrations, are also reviewed. The current recommendation of the authors is to treat patients with known coronary artery disease or those who are considered to be at high risk for coronary artery disease with 400 microg of folate supplementation. Until prospective clinical trial data become available, this approach appears to be a safe and effective way to approach this patient population. PMID- 11195621 TI - Percutaneous retrieval of a large peripherally inserted central catheter remnant from the pulmonary arteries. PMID- 11195622 TI - Which fasting triglyceride levels best reflect coronary risk? Evidence from the Turkish Adult Risk Factor Study. AB - BACKGROUND: Association between raised low-density lipoprotein cholesterol (LDL C) levels and high risk for coronary heart disease (CHD) is well established and taken into account in guidelines on coronary prevention. HYPOTHESIS: The relationship between risk for coronary heart disease (CHD) and the levels of fasting plasma triglycerides was studied in the cohort of the Turkish Adult Risk Factor Study, a representative random sample of an adult population. METHODS: In 829 men and 907 women aged > or =27 years (mean 48.5+/-11), plasma lipids and lipoproteins were measured by the enzymatic dry method in the postabsorptive state. A sample of values was validated in a reference laboratory. Apoliprotein (apo) A-I and B were measured by the turbidimetric immunoassay using commercial kits in part of the cohort. Blood pressure and anthropometric measurements were made. Criteria for the diagnosis of CHD were based on history, cardiovascular examination, and Minnesota coding of resting electrocardiograms. Coronary heart disease was diagnosed in about 7% of the subjects. Participants were divided into four categories depending on their triglyceride levels: I = < 100 mg/dl (282 men, 400 women), II = 100-139 mg/dl (204 men, 228 women), III = 140-212 mg/dl (188 men, 180 women), and IV = > or = 212 mg/dl (155 men, 99 women). RESULTS: After adjustment for age, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, smoking, and body mass index by logistic regression analysis, and after assigning the CHD risk of 1 to Category I, the relative risk for men and women combined rose to 1.42 in Category III (p<0.045) while it diminished to 0.94 in Category IV (p = 0.79). In women, the odds ratio (OR) rose gradually up to 1.78 (p< 0.025) in Category III, only to decline in Category IV. The OR in men was slightly, insignificantly, and equally elevated in Categories III and IV. Patients with CHD in Category III were not distinguished from those in Category IV by the studied risk parameters. It was suggested that high risk for CHD- particularly in subjects with slightly elevated or normal cholesterol levels-is often not reflected by extreme increases of fasting triglycerides but best by modest elevations (140-212 mg/dl), which serve better as a marker of triglyceride rich lipoprotein particles. This knowledge may prove to be of value in population screening and individual risk assessment. PMID- 11195623 TI - Single left coronary artery with origin of the right coronary artery from distal circumflex. AB - We report two very unusual cases of agenesis of the right coronary ostium with continuation of the left circumflex artery as the right coronary artery. The recognition of the anomaly in the first case lead to a better understanding of this finding in the second case, which translated into shorter procedure time, less contrast volume, and fewer catheter manipulations. PMID- 11195624 TI - John Collins Warren. PMID- 11195625 TI - Molecular characterization of an infectious bronchitis virus strain isolated from an outbreak in vaccinated layers. AB - An infectious bronchitis virus (IBV) strain CT/7852/97 was isolated from a commercial layer flock experiencing decreased egg production and poor egg quality. Reciprocal virus neutralization test demonstrated that the isolate was closely related to Massachusetts, Arkansas, and JMK. With the use of both reverse transcription-polymerase chain reaction-restriction fragment length polymorphism and multiplex polymerase chain reaction methods, results consistently showed that CT/7852/97 isolate was Massachusetts serotype specific only. The nucleotide sequence of S1 polypeptide coding region of CT/7852/97 was determined and compared with the published sequences of 12 IBV strains from North America. The highest nucleotide homology with H120 (97%) and the least homology (62%) with Delaware (De/072/92) were observed. Massachusetts 41 and Beaudette shared 94% and 93%, respectively, nucleotide similarity with CT/7852/97, and Connecticut, JMK, and Arkansas 99 had 94%, 83%, and 78%, respectively, nucleotide similarity with CT/7852/97. Furthermore, no possible recombination site on S1 gene among Massachusetts 41, Arkansas 99, and JMK was detected in the isolate. PMID- 11195626 TI - Analysis of semen quality from each testis/duct system of a turkey with a duplicated cloaca and vent. AB - A case is described wherein a turkey male (tom) possessed two vent areas with duplicated cloacae served by one large intestine. Both cloacae were functional in that feces were excreted and semen could be collected from each. The left vas deferens and ureter emptied into the left cloaca, and the right vas deferens and ureter emptied into the right cloaca. This allowed semen from each testis/duct to be collected separately from the corresponding cloaca. Thus, a unique opportunity was presented to collect semen separately from the left and right testis/duct system for semen analysis and fertility determination. Sperm concentration and percentage of dead sperm were not significantly different when semen from left vs. right reproductive tract were compared. The concentrations of spermiophages in semen from both reproductive tracts fell into the range reported for normal semen (0-8 x 10(5)/ml); however, semen from the right side had consistently higher spermiophage concentrations than that from the left side. On the basis of observations from one male made possible by an anatomic anomaly, it appears that the fecundities of the left and right testis/duct systems of the turkey male do not significantly differ and that recruitment of spermiophages into one tract (because of immunologic challenge, etc.) does not necessarily mean that the opposite testis/ducts will respond similarly. PMID- 11195627 TI - Diagnosis of eastern equine encephalitis by immunohistochemistry in two flocks of Michigan ring-neck pheasants. AB - The diagnosis of eastern equine encephalitis (EEE) virus infection in avian species is relatively difficult when compared with other species. There are no characteristic histologic lesions in the avian brain that would serve to distinguish EEE from infections with, for example, Newcastle disease or highly pathogenic avian influenza virus. Traditionally, virus isolation (VI) and/or hemagglutination inhibition (HI) has been used for a definitive diagnosis of EEE in birds. Recently, we developed an immunohistochemistry (IHC) technique for confirmatory diagnosis of EEE infection in equine brain. This test also detected EEE virus in formalin-fixed avian brain. VI confirmed IHC finding in two cases of EEE in ring-neck pheasants. IHC is a rapid, sensitive test for confirming and differentiating a histopathologic diagnosis of EEE in avian species and should be considered as an alternative test to VI or HI. PMID- 11195628 TI - Infection of turkeys with Ornithobacterium rhinotracheale and Mycoplasma synoviae. AB - Within 1 mo, two separate outbreaks of respiratory disease occurred in two flocks on the multiage market turkey farm in Slovenia. More severe dinical signs and higher mortality were observed in male birds. Ornithobacterium rhinotracheale (ORT) was isolated in pure culture from tracheas of the affected birds in both outbreaks. Commercial enzyme-linked immunosorbent assay test showed the presence of antibodies to ORT in sera of birds from both clinically affected flocks and also in two flocks of younger birds without clinical sings. Immunoblotting with ORT culture isolated during the outbreak as an antigen confirmed the presence of antibodies to ORT in sera of turkeys of all four flocks examined. In addition, three different serologic assays also detected antibodies to Mycoplasma synoviae (MS) in three out of four flocks. The concomitant infection with MS did not show an obvious effect on mortality rates nor on the antibody response against ORT. Younger birds appeared to be less susceptible to ORT pathogenicity because in those flocks the infection was subclinical. PMID- 11195629 TI - Experimental Escherichia coli respiratory infection in broilers. AB - This study determined optimal conditions for experimental reproduction of colibacillosis by aerosol administration of avian pathogenic Escherichia coli to 2-to-4-wk-old broiler chickens. The basic model for reproducing disease was intranasal administration of approximately 10(4) mean embryo infectious dose of infectious bronchitis virus (IBV) followed by aerosol administration of an 02 or an 078 strain of E. coli in a Horsfall unit (100 ml of a suspension of 10(9) colony-forming units/ml over 40 min). Scores were assigned to groups of infected chickens on the basis of deaths; frequency and severity of lesions in the air sacs, liver and heart; and recovery of the challenge E. coli 6 days post-E. coli infection. An interval of 4 days between the IBV and E. coli challenges was best whether the chickens received the IBV at 8 or 20 days of age. Typically, 50%-80% of the chickens developed airsacculitis and 0 to 29% of the chickens developed pericarditis or perihepatitis, with little or no mortality. Escherichia coli alone resulted in no deaths and 0 to 20% airsacculitis, but these percentages increased to 0 to 5% and 52%-60% when the E. coli aerosol was administered through a cone-shaped chamber. Administration of IBV alone failed to induce lesions. Recovery of the challenge E. coli from chickens did not correlate well with lesions. On the basis of these data, administration of IBV to 20-day-old chickens followed 4 days later by exposure to an avian pathogenic E. coli reproduces avian colibacillosis with the low mortality, high percentage of airsacculitis, and low percentage of septicemic lesions characteristic of the conditions seen in the natural disease. PMID- 11195630 TI - Development of a quantitative-competitive polymerase chain reaction assay for serotype 1 Marek's disease virus. AB - We have developed a quantitative-competitive (QC) polymerase chain reaction (PCR) for the detection of Marek's disease virus (MDV) DNA. The assay utilizes a competitor DNA that differs from the viral DNA of interest by having a small insertion. The competitor DNA acts as an internal standard for the estimation of viral DNA in an unknown sample. The amount of viral DNA in a sample is quantitated by coamplification in the presence of a known amount of competitor DNA. The same PCR primers that amplify the viral DNA also amplify the competitor DNA. When the amount of competitor is equal to the amount of viral DNA in a sample, there is equal amplification of the competitor and the virus. Thus, we are able to quantitate the viral DNA in an unknown sample. To establish the utility of this assay, in vivo correlations between virulence and virus replication were studied. Our data demonstrated that a more virulent strain of MDV (648A) replicated better in thymus during cytolytic infection than did a less virulent strain (GA). However, no differences in virus titer were observed when these two viruses were propagated in tissue culture. Our data are consistent with the generally held idea that "hot" strains of MDV replicate earlier and better in birds. Thus, QC-PCR is extremely specific and sensitive to measure MDV DNA over a wide range and can be applied to in vivo studies of viral pathogenesis. PMID- 11195631 TI - Interaction of Marek's disease virus and Cryptosporidium baileyi in experimentally infected chickens. AB - Histocompatible B13/B13 white specific-pathogen-free leghorn chickens were used to investigate the effect of coinfection with Cryptosporidium baileyi and the HPRS 16 strain of Marek's disease virus (MDV) in chickens and to assess the pathogenicity of C. baileyi when MDV is given before or after the parasite. Groups of chickens concurrently infected with C. baileyi orally inoculated at day (D)4 and MDV inoculated at hatching (C4M0 group) or at D8 (C4M8 group) were compared with relevant control groups inoculated with only C. baileyi at D4 (C4 group), only MDV at hatching (M0 group) or at D8 (M8 group), and an uninoculated control group (UC group). The chickens were kept in isolator units until the end of the experiment at D62. Our results showed a considerable synergistic effect in concurrently infected chickens and more severe consequences when chickens received MDV before C. baileyi infection. In fact, except for a slight transitory weakness, the chickens in C4 group remained free of overt clinical signs and there was no mortality. However, coinfection with both pathogens induced more lasting or permanent oocyst shedding. Severe clinical cryptosporidiosis with weakness, anorexia, depression, growth retardation, and chronic and severe respiratory disease causing death occurred in all chickens in the C4M0 group between D12 and D43 and in 67% of the chickens in the C4M8 group between D17 and D57. Eighty-two percent and 33%, respectively, died before the development of specific Marek's disease lesions. Mortality rates were 27% and 33% in the M0 and M8 groups, respectively. The presence of MDV enhanced the establishment of more lasting cryptosporidial infection in the respiratory tract, esophagus, crop, proventriculus, and kidneys (only in C4M0 group) as well as in bursa of Fabricius, ceca, and cloaca. Serologic analysis showed that chickens with chronic cryptosporidiosis in the C4M8 group had an increased level of C. baileyi-specific immunoglobulin A. Our results may explain some cases of mortality in chickens naturally infected with MDV and Cryptosporidium. PMID- 11195632 TI - Nonspecific innate immunity against Escherichia coli infection in chickens induced by vaccine strains of Newcastle disease virus. AB - The objective was to test the hypothesis that vaccine strains of Newcastle disease virus (NDV) induce nonspecific immunity against subsequent infection with Escherichia coli. White leghorn chickens at 5 wk of age were vaccinated with a NDV vaccine at various days before challenge exposure with O1:K1 strain of E. coli via an intra-air sac route. Immunity was determined on the basis of the viable number of E. coli in the spleen 24 hr after the infection. Roakin strain induced significant (P < 0.05) immunity against E. coli at 4, 6, and 8 days, and La Sota strain at 2, 4, and 8 days, postvaccination. Secondary NDV vaccination administered 14 days later failed to induce immunity against E. coli when chickens were infected 1 or 5 days after the vaccination. Significant (P < 0.05) suppression of this nonspecific immunity was observed in birds treated with corticosterone, 40 mg/kg in feed, given for three consecutive days immediately prior to the bacterial exposure but not in those treated prior to the period. The results indicate that innate immunity induced by the primary NDV vaccination may significantly suppress the multiplication of E. coli in chickens for a period of 2-8 days postvaccination. The NDV-induced immunity was inhibited by corticosterone, which is known to mediate physiological responses to stress. PMID- 11195633 TI - Susceptibility of broiler chicks to infection by avian pneumovirus of turkey origin. AB - In this paper we present the results of studies on the infectivity of an isolate of avian pneumovirus (APV) from turkeys to broiler chickens. Two-week-old broiler chicks free of antibodies to APV were exposed either by oculonasal or oral route with a cell cultured APV of turkey origin. Chickens from both APV-inoculated groups exhibited clinical signs that included coughing, sneezing, nasal discharge, and watery eyes during 2-8 days postinoculation. Tissue samples from birds in the APV-inoculated group were positive for APV by polymerase chain reaction (PCR) up to 9 days postinoculation. Samples of blood from both oculonasally and orally infected chickens were positive for APV. Intestinal samples from chickens infected with APV orally were positive for the presence of APV on PCR up to 9 days postinoculation. APV was reisolated from samples taken from chickens in both groups inoculated orally and oculonasally. Sera from birds exposed by the oculonasal or by the oral route showed the presence of APV specific antibodies. PMID- 11195634 TI - Evaluation of chicken infectious anemia virus and associated risk factors with disease and production losses in broilers. AB - A case-control study was performed to determine the significance of chicken infectious anemia virus (CIAV) as a risk factor associated with secondary disease in commercial broilers and to identify the significance of production losses associated with CIAV. The study also examined the relationship between bursal and thymic atrophy and the presence of CIAV. Cases were defined as submissions to the Alabama Veterinary Diagnostic Laboratories with a history of clinical disease and with a diagnosis of coccidiosis, gangrenous dermatitis, or respiratory disease. Controls were selected from submissions with neither a history of disease nor evidence of disease on necropsy. CIAV was detected in fresh tissues by polymerase chain reaction. Both thymic atrophy and the detection of CIAV were significantly associated with a disease case (P < 0.05). Bursal atrophy was a significant risk factor associated with the detection of CIAV in a submission (P < 0.05). Whereas CIAV was associated with disease cases that showed production losses in both percentage of livability and percentage of condemnations (P < 0.05), detection of CIAV alone was not associated with detectable losses in production or flock performance. PMID- 11195635 TI - Induction of vitamin A deficiency in turkeys. AB - The objective of this study was to determine the relationship between the hepatic vitamin A (VitA) level and the pathologic changes in the oropharynx and esophagus of VitA-deficient turkeys. Study turkeys were provided with a diet sufficient (11,000 IU/kg) or deficient (2750 IU/kg) in VitA from 4 to 17 wk of age. Body weight, bacterial culture, and tissues from internal organs were collected at weekly intervals. VitA deficiency causes epithelial tissue damage in poultry. This epithelial damage was seen grossly as white plaques in the oropharynx and esophagus and histologically as squamous metaplasia of mucosal glands and keratinization of epithelium. No significant difference in body weights was seen among the groups. Moreover, no pathogenic bacteria was isolated during sampling periods. Liver VitA levels declined significantly after consumption of low VitA diet for 3 wk and were depleted after 5 wk. Squamous metaplasia due to VitA deficiency developed in the esophagus after 3 wk and in the oropharynx after 4 wk of consuming a VitA-deficient diet. PMID- 11195636 TI - The effect of hypovitaminosis A on the pathogenesis of Pasteurella multocida in turkeys. AB - It has been proposed that Pasteurella multocida can invade the host tissues via the mucous membrane. Vitamin A (VitA) deficiency has been associated with mucous membrane damage, such as squamous metaplasia. The objective of this study was to determine the early stages in the pathogenesis of P. multocida in VitA-deficient turkeys and clinically healthy turkeys. Fifteen-week-old VitA-deficient and clinically healthy turkeys were inoculated with P. multocida P-1059, a virulent strain, and the portal of entry, invasion, and localization of P. multocida were studied by microbial examination of the trachea, liver, and lung and histologic examinations of internal organs. Higher mortality was found in VitA-deficient turkeys. Pasteurella multocida was first reisolated from the trachea, secondarily from the liver and blood, and finally from the lung in both groups. Invasion of P. multocida into tissues occurred between 3 hr and 24 hr postinoculation in both groups. Our findings suggest that altered membrane integrity in VitA-deficient birds did not appear to change the time course of the systemic spread of P. multocida infection in turkeys and that the increased mortality seen in the VitA deficient turkeys may be associated with immune system impairment. PMID- 11195637 TI - Reticuloendotheliosis virus (REV) long terminal repeats incorporated in the genomes of commercial fowl poxvirus vaccines and pigeon poxviruses without indication of the presence of infectious REV. AB - Because of reticuloendotheliosis virus (REV) contamination in commercial poultry vaccines, polymerase chain reaction (PCR) assays have been described to increase the sensitivity of biological assays used to detect REV in vaccines. The PCR assay designed to amplify the long terminal repeat (LTR) region of REV identified REV LTRs in many of the commercial fowl poxvirus (FPV) vaccines evaluated. These commercial vaccines were not thought to be contaminated with replicating REV because of the lack of REV outbreaks, the lack of in vitro amplification, and lack of a serologic response to REV. As previously described, the FPV S vaccine strain is known to carry infectious integrated proviral REV, whereas FPV M vaccine strain and its derivatives carry integrated LTRs or remnants of REV proviral DNA inserted into the FPV genome. Another PCR assay designed to amplify the envelope gene of REV was used to verify that the envelope proviral gene was not present in REV LTR PCR-positive samples. Southern blot analysis with REV LTR probes hybridized to the 9-kb EcoRI genomic fragment of all FPV and pigeon poxviruses evaluated, whereas the envelope probe did not hybridize to any poxvirus genome. Sequence analysis of the 9-kb EcoRI fragment indicated that an integrated REV LTR exists in the 9-kb EcoRI of some poxvirus genomes. A new PCR assay designed to amplify integrated REV LTRs in the 9-kb EcoRI fragment identified complete and incomplete integrated REV LTRs in all FPV and pigeon poxvirus genomes evaluated. PMID- 11195638 TI - Viral pathogenesis in chicken embryos and tumor induction in chickens after in ovo exposure to serotype 1 Marek's disease virus. AB - We examined the susceptibility of late-stage chicken embryos to infection with oncogenic serotype 1 Marek's disease virus (MDV 1). Intravenous inoculation of MDV 1 at embryonic day (ED) 16 resulted in significant replication of the virus in embryonic tissues. Within 5 days of virus exposure, pp38 viral antigen (pp38) was detected in embryonic bursae and MDV 1 was isolated by plaque assay from the spleens, thymuses, and bursae of embryos. The pathogenesis of MDV 1 after intravenous inoculation at ED 16 was similar to that in chicks exposed to MDV 1 after hatching. In contrast to the response of the embryo to intravenous inoculation, embryos exposed to MDV 1 by the amniotic route did not develop detectable pp38, nor could the virus be isolated from the embryonic tissues by plaque assay. These results show that the route of inoculation of MDV 1 in the embryos is critical for allowing the virus to come in contact with target cells. PMID- 11195639 TI - Survival of Salmonella typhimurium and Escherichia coli O157:H7 in poultry manure and manure slurry at sublethal temperatures. AB - Exponential inactivation was observed for Salmonella typhimurium and Escherichia coli O157:H7 in poultry manure with decimal reduction times ranging from half a day at 37 C to 1-2 wk at 4 C. There was no material difference in inactivation rates between S. typhimurium and E. coli O157:H7. Inactivation was slower in slurries made by mixing two parts of water with one part of manure; decimal reduction times (time required for 90% destruction) ranged from 1-2 days at 37 C to 6-22 wk at 4 C. Escherichia coli O157:H7 consistently exhibited slightly slower inactivation than S. typhimurium. Log decimal reduction time for both strains was a linear function of storage temperature for manure and slurries. Chemical analysis indicated that accumulation of free ammonia in poultry manure was an important factor in inactivation of the pathogens. This finding was experimentally confirmed for S. typhimurium by adding ammonia directly to peptone water or to bovine manure, which was naturally low in ammonia, and adjusting pH to achieve predetermined levels of free ammonia. PMID- 11195640 TI - The effect of eukaryotic expression vectors and adjuvants on DNA vaccines in chickens using an avian influenza model. AB - Vaccination of poultry with naked plasmid DNA has been successfully demonstrated with several different poultry pathogens, but the technology needs to be further developed before it can be practically implemented. Many different methods can conceivably enhance the efficacy of DNA vaccines, and this report examines the use of different eukaryotic expression vectors with different promoters and different adjuvants to express the influenza hemagglutinin protein. Four different promoters in five different plasmids were used to express the hemagglutinin protein of an H5 avian influenza virus, including two different immediate early cytomegaloviruses (CMVs), Rous sarcoma virus, chicken actin, and simian virus 40 promoters. All five constructs expressed detectable hemagglutinin protein in cell culture, but the pCI-neo HA plasmid with the CMV promoter provided the best response in chickens when vaccinated intramuscularly at 1 day of age on the basis of antibody titer and survivability after challenge with a highly pathogenic avian influenza virus at 6 wk postinoculation. A beneficial response was observed in birds boostered at 3 wk of age, in birds given larger amounts of DNA, and with the use of multiple injection sites to administer the vaccine. With the use of the pCI-neo construct, the effects of different adjuvants designed to increase the uptake of plasmid DNA, including 25% sucrose, diethylaminoethyl dextran, calcium phosphate, polybrene, and two different cationic liposomes, were examined. Both liposomes tested enhanced antibody titers as compared with the positive controls, but the other chemical adjuvants decreased the antibody response as compared with the control chickens that received just the plasmid alone. The results observed are promising for continued studies, but continued improvements in vaccine response and reduced costs are necessary before the technology can be commercially developed. PMID- 11195641 TI - Relationship between antigen release and antibody response of infectious coryza water-in-oil-in-water emulsion vaccines. AB - The relationship between the antigen release from formulations in vitro and the antibody response after administration of water-in-oil-in-water (W/O/W) emulsion vaccines containing Haemophilus paragallinarum (Hpg) was studied in chickens. Increases of sorbitan sesquioleate volume in the formulation led to slower antigen release and tended to induce higher hemagglutination-inhibition (HI) antibody titers. In addition, the vaccines prepared with internal aqueous phase:oil phase:external aqueous phase (A:O:A) ratios of 3:4:3 and 3:3:4 also showed slower release of antigen and higher HI antibody titer compared with those of an A:O:A ratio of 3:2:5. Vaccines prepared with polyoxyethylene (POE)(10) hydrogenated castor oil or POE(40) hydrogenated castor oil instead of sorbitan sesquioleate showed higher release and lower antibody HI titers. As a result, HI antibody titers at 6 wk after vaccination were inversely related to antigen release, as determined by the release test. The correlation coefficient was 0.942. In infectious coryza W/O/W emulsion vaccines, the slow release of antigen from the formulation induced and maintained high HI antibody titers of Hpg. PMID- 11195642 TI - Antibody titers to infectious bursal disease virus in broiler chicks after vaccination at one day of age with infectious bursal disease virus and Marek's disease virus. AB - The effect of day-of-age vaccination with infectious bursal disease virus (IBDV) alone or in combination with Marek's disease virus (MDV) in broiler chicks was investigated. One-day-old commercial broiler progeny obtained from IBDV-immunized breeder flocks were vaccinated subcutaneously according to the manufacturer's directions with live-attenuated commercially available vaccines as follows: IBDV alone, MDV alone, IBDV + MDV, and unvaccinated control. IBDV was not detected after vaccination by reverse transcriptase/polymerase chain reaction in any of the bursal, thymic, and splenic tissues tested. Serum IBDV antibody levels, as monitored by enzyme-linked immunosorbent assay (ELISA), showed similar rates of decline among the four groups, and, by day 28 postinoculation, serum antibody levels in all groups were below detectable limits. IBDV-specific neutralizing maternal antibody (MA) titers in the IBDV + MDV and control groups, as monitored by the virus neutralization assay (VN), remained higher and declined more slowly throughout the experiment as compared with VN titers in the IBDV- and the MDV vaccinated groups. In a second experiment, groups of one-day-old broiler chicks were vaccinated as in Experiment 1. Serum IBDV antibody detected by ELISA and VN assay declined parallel to those observed in Experiment 1. Histopathologic lesions characteristic of IBDV were not observed in any of the groups. Vaccination with MDV alone was associated with increased rates of IBDV neutralizing MA decline similar to those caused by vaccination with IBDV alone, whereas concurrent vaccination with IBDV + MDV was not associated with increased rates of IBDV neutralizing MA decline over that of nonvaccinated controls. Results of these studies indicate that IBDV vaccination at 1 day of age does not cause accelerated IBDV-specific MA decline as detected by ELISA but does appear to cause an accelerated decline in neutralizing IBDV-specific MA. Furthermore, vaccination with IBDV at 1 day of age appeared to slow the accelerated rate of IBDV neutralizing antibody decline caused by MDV vaccination. PMID- 11195643 TI - Hematologic and clinical chemistry reference values in red lories (Eos spp.). AB - We established reference ranges for three hematologic and 15 clinical chemistry parameters of 40 clinically healthy birds of the genus Eos. The following species were included to the study: Eos histrio (n = 19), Eos squamata (n = 8), Eos bomea (n = 5), Eos reticulata (n = 4), Eos cyanogenia (n = 4). Detailed information concerning methodology, which is often missing in papers dealing with reference values, is included. As far as possible, data are compared with literature, and some thoughts on obvious deviations are given. The problem of establishing reference values in rare species is reviewed. PMID- 11195644 TI - Alterations in levels of various host antioxidant factors in turkey knockdown syndrome. AB - Five components (selenium, glutathione peroxidase, copper, superoxide dismutase, and vitamin E) of the antioxidant system of turkey poults were examined to determine if they play any role in the knockdown (KD) syndrome. All flocks were provided with feed formulated to contain monensin at 54-60 g/ton. Flock data were analyzed as a case-control study with three treatment groups (KD-affected and unaffected turkey poults from a KD flock and poults from an unaffected flock [control]). Affected turkey poults had lower (P < 0.001) serum vitamin E levels compared with unaffected poults from KD flocks or poults from unaffected flocks. No significant differences were observed for the other parameters evaluated but there was a trend towards lower copper and superoxide dismutase values in affected birds. It appears that serum vitamin E concentrations in turkey poults may play a significant role in susceptibility to or protection against KD syndrome. Other components of the antioxidant system may also be involved, and complex interactions among several body systems may be critical. PMID- 11195645 TI - Ornithobacterium rhinotracheale, a primary pathogen in broilers. AB - Field strains of Ornithobacterium rhinotracheale were tested on their virulence in different chicken breeds. Ornithobacterium rhinotracheale was able to induce lesions after aerosol challenge without a previous priming with virus, and thus O. rhinotracheale was proven to be a primary pathogen. The virulence of Dutch strains, isolated between 1995 and 1998, did not increase, but the Dutch isolates and a South African strain were more pathogenic compared with an American strain of O. rhinotracheale. White specific-pathogen-free leghorns were less susceptible to O. rhinotracheale infection than broilers, whereas there was no difference in susceptibility between commercial broilers and specific-pathogen-free broilers. PMID- 11195646 TI - In vitro effect of ethylenediaminetetraacetic acid-Tris on the efficacy of hatchery disinfectants. AB - Solutions of ethylenediaminetetraacetic acid (EDTA)-Tris showed synergistic or additive effects on gram-negative bacteria when combined with hatchery disinfectants consisting of phenol and detergent (Magnaphen-100), quaternary ammonium compound (QAC) and glutaraldehyde (Synergize), QAC (BioSentry 904), and hydrogen peroxide. The gram-positive bacteria reacted less favorably, with reaction mixtures showing all three levels of potentiation (synergistie, additive, and antagonistic). Combinations of EDTA-Tris and a commercial glutaraldehyde solution (Glutracide), when mixed with the test organisms, showed mostly antagonistic effects. Solutions of EDTA-Tris decreased the concentration of hatchery disinfectants required for bacterial killing by 75% in those situations in which synergistic potentiation occurred. EDTA-Tris is nontoxic to 12-day-old embryos. Serial passage of the test organisms in solutions of EDTA Tris did not result in the development of resistant forms. PMID- 11195647 TI - Genotyping Campylobacter jejuni strains isolated from the gut and oviduct of laying hens. AB - Campylobacter jejuni frequently colonizes the avian intestine. Recent evidence suggests that this organism can also colonize the oviduct of laying hens. However, the source and role of this colonization are unknown. Isolates from the ceca, cloacae, and oviducts of 11 laying hens in three intensive egg-producing flocks were genotyped by Fla typing with the restriction fragment length polymorphism of the polymerase chain reaction product of the flaA and flaB genes (fla typing) and pulsed-field gel electrophoresis (PFGE). A diversity in fla types and PFGE types was observed within and between flocks. Individual birds could be colonized by different genotypes at various intestinal and oviduct sites. However, the oviduct of individual birds appeared to be colonized by only one genotype at the time of sampling. In two birds, matching isolates investigated from the intestinal and reproductive tracts were genotypically identical but different from those oviduct isolates found in other birds in the same flock. Interestingly, not all cecal isolates appeared to be equally able to colonize the oviduct. These results suggest that oviduct colonization may result from ascending infection via the cloaca and that some strains of C. jejuni may be better adapted than others to oviduct colonization. PMID- 11195648 TI - Avian leukosis virus subgroup J infection profiles in broiler breeder chickens: association with virus transmission to progeny. AB - Profiles of infection with avian leukosis virus subgroup J (ALV-J) and factors that predict virus transmission to progeny were studied. Eggs from an infected broiler breeder flock were hatched at the laboratory. The flock was reared in a floor pen, transferred to laying cages at 22 wk, and inseminated to produce fertile eggs. A cohort of 139 chickens was tested at frequent intervals over a 62 wk period for virus, viral antigens, or antibodies in plasma, cloacal swabs, egg albumen, and embryos. Virus was detected in 7% of chicks at hatch but spread rapidly so that virtually all chicks became infected between 2 and 8 wk of age. Mortality due to myeloid leukosis and related tumors was 22%. Over 40% of the chicks developed persistent infections, whereas the remainder experienced transient infections. Five types of infection profiles were recognized. Novel responses included hens that were positive for virus intermittently or started late in life to shed viral antigens into the cloaca. ALV-J was isolated from 6% of 1036 embryos evaluated between 26 and 62 wk. However, over 90% of the virus positive embryos were produced between 29 and 34 wk of age. Of 80 hens that produced embryos, 21 produced at least one infected embryo and were identified as transmitters. All but one transmitter hen would have been detected by a combination of viremia, cloacal swab, and albumen tests conducted between 18 and 26 wk. However, virus was transmitted to embryos from hens that were not persistently viremic or that rarely shed viral group-specific antigen into the albumen of their eggs. Intermittent patterns of both antigen shedding and virus transmission to embryos were observed in some hens. These results validate current screening procedures to identify potential transmitter hens and provide some suggestions for improvement but also show that identification of all transmitter hens by such procedures is unlikely. Thus, eradication programs based solely on dam testing may be less effective than those where dam testing is combined with procedures to mitigate early horizontal transmission in progeny chicks. PMID- 11195649 TI - Pathogenicity of West Nile virus for turkeys. AB - In the fall of 1999, West Nile virus (WNV) was isolated during an outbreak of neurologic disease in humans, horses, and wild and zoological birds in New York, Connecticut, and New Jersey. Turkeys could potentially be a large reservoir for WNV because of the high-density turkey farming and the presence of large wild turkey populations in the eastern seaboard of the United States. Little is known about the pathogenicity of WNV in domestic or wild turkeys. Specific-pathogen free 3-wk-old turkeys were inoculated subcutaneously with 10(3.3) mean tissue culture infective doses of a WNV strain isolated fromthe index case in a New York crow. No clinical signs were observed in the turkeys over the 21 days of the experiment. One turkey died abruptly at 8 days postinoculation (DPI). Many turkeys developed viremia between 2 and 10 DPI, but the average level of virus was very low, less than needed to efficiently infect mosquitos. Low levels of WNV were detected in feces on 4 and 7 DPI, but no virus was isolated from oropharyngeal swabs. WNV wasnot transmitted from WNV-inoculated to contact exposed turkeys. All WNV-inoculated poults seroconverted on 7 DPI. In the turkey that died, WNV was not isolated from intestine, myocardium, brain, kidney, or cloacal and oropharyngeal swabs, but sparse viral antigen was demonstrated by immunohistochemistry in the heart and spleen. Turkeys in contact with WNV inoculated turkeys and sham-inoculated controls lacked WNV specific antibodies,and WNV was not isolated from plasma and cloacal and oropharyngeal swabs. These data suggest that WNV lacks the potential to be a major new disease of turkeys and that turkeys will not be a significant amplifying host for infecting mosquitos. PMID- 11195650 TI - A multiplex reverse transcription-polymerase chain reaction assay for Newcastle disease virus and avian pneumovirus (Colorado strain). AB - Newcastle disease virus (NDV) and avian pneumovirus (APV) cause Newcastle disease and rhinotracheitis respectively, in turkeys. Both of these viruses infect the respiratory system. A one-tube, multiplex, reverse transcription-polymerase chain reaction (RT-PCR) assay for the detection of both NDV and Colorado strain of APV (APV-Col) was developed and evaluated. The primers, specific for each virus, were designed from the matrix protein gene of APV-Col and the fusion protein gene of NDV to amplify products of 631 and 309 nucleotides, respectively. The multiplex RT-PCR assay, for detecting both viruses simultaneously, was compared with the single-virus RT-PCR assays for its sensitivity and specificity. The specific primers amplified products of predicted size from each virus in the multiplex as well as the single-virus RT-PCR assays. The multiplex RT-PCR assay was determined to be equivalent to the single-virus RT-PCR assays for detecting both NDV and APV Col. This multiplex RT-PCR assay proved to be a sensitive method for the simultaneous and rapid detection of NDV and APV-Col. This assay has the potential for clinical diagnostic applications. PMID- 11195651 TI - Characterization of Mexican strains of avian infectious bronchitis isolated during 1997. AB - Ten infectious bronchitis virus (IBV) isolates were recovered from broiler chickens in the states of Queretaro and Guanajuato in Mexico. The viruses were isolated from trachea, lung, kidney, and cecal tonsils of birds that showed respiratory signs in spite of vaccination with Massachusetts (Mass) and Connecticut strains of IBV. Each isolate was identified by an accession number from 1 to 10. Six of the isolates were neutralized by Mass monoclonal antibodies, whereas the other four were not. In addition, these four isolates did not produce lesions in embryos in the first five to seven passes. These four isolates were further characterized by the reverse transcriptase-polymerase chain reaction and restriction fragment length polymorphism techniques. The electrophoretic patterns for the four isolates were identical but were different from other known IBV isolates. PMID- 11195652 TI - Maintenance of a captive flock of house finches free of infection by Mycoplasma gallisepticum. AB - Since the beginning of an epidemic of conjunctivitis in wild house finches caused by Mycoplasma gallisepticum (MG), all captive colonies established by capturing free-ranging house finches from the eastern population have also either been infected at the time of capture or developed infection shortly after capture. In an attempt to avoid this infection in captive flocks being maintained for studies of the finches' behavior and ecology, we compared two different flock management strategies and were able to prevent the development of mycoplasmal conjunctivitis with one of the strategies. Single-sex flocks were built by introducing only seronegative wild-caught birds showing no clinical signs of conjunctivitis and covering their outdoor flight cages with netting to prevent interaction with other wild birds although only the female flocks were initially treated with a 6 wk course of tylosin tartrate (0.3 mg/ml). The female flocks never developed conjunctivitis although the disease did develop in the male flocks. Furthermore, serologic assessments of the healthy flock by serum plate agglutination assays for MG indicated that the females remained free of MG infection in the final 7 wk of the study, during which they were unmedicated. We conclude that any low-level MG infection not diagnosed by the initial test for seroconversion was cleared by the prolonged drug treatment. PMID- 11195653 TI - Health status of northern bobwhite quail (Colinus virginianus) in eastern Kansas. AB - The health status of wild northern bobwhite quail (Colinus virginianus) from Lyon County, Kansas, was evaluated by conducting comprehensive health assessments on 25 birds. Gross lesions indicative of avian pox, ulcerative enteritis, and quail bronchitis were not present. Serologic tests for antibodies to Salmonella pullorum, Salmonella gallinarum, Pasteurella multocida, Mycoplasma gallisepticum, Mycoplasma synoviae, and avian adenoviruses were all negative. Intestinal coccidia (Eimeria spp.) were found in 36% of the birds. Only three species of helminth parasites were found: Dispharynx nasuta in two birds, Cyrnea colini in one bird, and larval Physaloptera sp. in four birds. Arthropod parasites (ticks, lice, mites, and/or chiggers) were present on 96% of the birds examined. Compared with wild bobwhite populations in the southeastern United States, the diversity, prevalence, and intensities of microbial and parasitic agents were low. PMID- 11195654 TI - Outer membrane proteins for serologic detection of Ornithobacterium rhinotracheale infection in turkeys. AB - Ornithobacterium rhinotracheale (ORT) is a bacterium responsible for a respiratory disease in turkeys and chickens and has been identified as one of the emerging respiratory bacterial pathogens. The clinical signs and lesions caused by ORT are very similar to those caused by other respiratory infectious agents; therefore, an accurate diagnostic test is necessary to identify the infection. In this study, we have investigated the use of outer membrane proteins of ORT in an indirect enzyme-linked immunosorbent assay (ELISA) to detect the exposure to ORT infection. Outer membrane proteins of ORT were extracted and used as an antigen in ELISA to detect infection in turkeys exposed to different serotypes of ORT. The ELISA results were compared with the conventional serum plate agglutination test. The agglutination test detected specific antibodies for ORT in 65% of experimentally infected turkeys during the first 2 wk of infection. The ELISA detected up to 100% of infected birds for 8 wk postinfection. The results suggest that ELISA is able to detect the exposure to ORT in later stages of the infection and this assay can be used in serologic surveillance of ORT infection for poultry in the field. PMID- 11195655 TI - Presence of fluoroquinolone-resistant coliforms in poultry litter. AB - Litter was collected from four turkey farms (eight houses) with a history of fluoroquinolone (FQ) treatment failure, 10 adult broiler breeder chicken farms (43 houses) with one having a history of FQ treatment, and 30 broiler chicken farms (110 houses) with 24 having a history of FQ treatment. In the turkey litter, the percentage of nalidixic acid-resistant (at 100 microg/ml) coliforms/total number of coliforms ranged from 0.6% to 61.9%. Two of the four farms had houses containing coliforms resistant to the two FQs, enrofloxacin (1 microg/ml) and sarafloxacin (1 microg/ml). There was also multiple resistance to other antimicrobials on all four turkey farms (ampicillin, tetracycline, chloramphenicol, kanamycin). The level of total coliforms from the adult broiler breeder litter was low, and there were no nalidixic acid-resistant isolates from any of the 10 farms. In the broiler chickens, 7 of 91 houses with a history of FQ usage contained coliforms resistant to nalidixic acid; however, 2 of the 19 houses on farms with no history of FQ usage had nalidixic acid-resistant coliforms. All of the broiler farms with nalidixic acid-resistant isolates were also resistant to the FQ sarafloxacin, whereas only 3 of the 24 treatment history farms and 1 of the no-treatment history farms exhibited enrofloxacin-resistant coliforms in the litter. PMID- 11195656 TI - Some safety aspects of salmonella vaccines for poultry: distribution and persistence of three Salmonella typhimurium live vaccines. AB - The purpose of this study was to analyze the safety characteristics of three commercially available live Salmonella vaccine strains (vacT, Zoosaloral, and X3985) in relation to their persistence in individual animals but also within a flock and in the environment. In a first experiment, the digestive and systemic distributions in chickens were followed for 10 days in individually reared chickens that were orally inoculated at 1 day of age. Strain X3985 quickly disappeared from the digestive tract but remained in the liver until the end of this experiment, whereas strains vacT and Zoosaloral colonized the liver as well as the gut for 10 days. In the second trial, behavior of the vaccine strains was studied in groups of 20 chickens during 10 wk after a single oral administration to individual birds. Strain vacT remained in the environment of inoculated animals for 4-5 wk. Six weeks after the inoculation, vacT was not recovered from internal organs such as liver and spleen, and vacT disappeared from the digestive tract between the sixth and the 10th weeks. Comparatively, both Zoosaloral and X3985 vaccine strains persisted longer in the environment (8 wk at least). Of the vaccine strains, X3985 showed the greatest colonization of both systemic and digestive organs. PMID- 11195657 TI - Lack of antigenic relationship between French and recent North American non-A/non B turkey rhinotracheitis viruses. AB - Twelve turkey rhinotracheitis viruses (TRTVs) including the Colorado isolate and two French non-A/non-B viruses were serologically compared. Six enzyme-linked immunosorbent assay (ELISA) antigens derived from subgroup A, subgroup B, a French non-A/non-B, and the Colorado TRTVs were used. Virus neutralization (VN) tests were performed with four Ma-104-adapted viruses derived from subgroup A, subgroup B, a French non-A/non-B, and the Colorado viruses. French strains isolated since 1995 were assigned to subgroup B in both ELISA and VN, whereas those isolated in 1985 and 1986 appeared more diverse: two strains belonged to subgroup B, one to subgroup A, and two others appeared antigenically different from both the A and B subgroups and are classified as non-A/non-B. The Colorado strain appeared different from these three groups of TRTVs. Assignment to subgroup A or B was confirmed by reverse transcription-polymerase chain reaction, but neither the French non-A/non-B strains nor the Colorado virus could be classified with the subgroup-specific G-based primers. These results suggest that at least three antigenically different viruses were present in France in 1985-86 and that the Colorado strain is different from all European TRTVs. Further serologic and phylogenic studies will be necessary to evaluate their actual prevalences and relationships. PMID- 11195658 TI - Sequential spread of Campylobacter infection in a multipen broiler house. AB - Generally, colonization with Campylobacter jejuni is first detected in broilers 2 3 wk after hatching. Once introduced into a flock, this infection spreads very rapidly. The sources and routes of transmission of C. jejuni in broilers remain debatable. In this study, the spread of infection was monitored in a commercial multipen broiler house in which birds were contained in discrete groups and sampled sequentially. Colonization was monitored in two broiler flocks up to slaughter. Serotyping and fla typing methods were applied to differentiate all the C. jejuni strains isolated. In flock 1, colonization was first detected at 32 days of age in birds located at the rear of the house. By 40 days, nearly all the birds were infected with the same strain (fla type 1.9). However, at 46 days of age, a second strain (fla type 3.7) was detected in some of the birds. These birds were also located toward the rear of the house. In flock 2, infection was detected at 5 wk of age. This infection was once again first detected in birds located at the rear of the house. In this flock, only a single fla type (1.1) was isolated throughout. A survey of the broiler house relative to the location of first point of infection indicated the use of an entrance door unprotected by boot dips. However, securing this door during the second flock study did not prevent infection. PMID- 11195659 TI - Serologic survey of slaughter-age ostriches (Struthio camelus) for antibodies to selected avian pathogens. AB - Serum samples from 163 slaughter-age ostriches (Struthio camelus) in Ohio and Indiana were tested for antibodies to avian influenza virus (AIV), Newcastle disease virus (NDV), paramyxovirus (PMV) 2, PMV3, PMV7, infectious bursal disease virus (IBDV), Bordetella avium, Mycoplasma synoviae, Mycoplasma gallisepticum, Ornithobacterium rhinotracheale, Salmonella pullorum, Salmonella gallinarum, and Salmonella typhimurium. One ostrich had antibodies to AIV H5N9, 57% of the ostriches had antibodies to NDV, four ostriches had antibodies to both NDV and PMV2, and one ostrich had antibodies to NDV, PMV2, PMV3, and PMV7. None of the ostriches had antibodies to IBDV, B. avium, M. synoviae, M. gallisepticum, O. rhinotracheale, S. pullorum, S. gallinarum, and S. typhimurium. This is the first report of antibodies to avian influenza and PMV7 in ostriches in the United States. PMID- 11195660 TI - National surveillance of Campylobacter in broilers at slaughter in Denmark in 1998. AB - A surveillance study for thermophilic Campylobacter spp. in broiler flocks was carried out for the year 1998 in Denmark. The study included examinations of 4286 broiler flocks comprising samples from 57,000 birds. Overall, a flock prevalence of 46.0% was recorded. The species distribution was Campylobacter jejuni 86%, Campylobacter coli 11%, Campylobacter lari 1%, other not further diagnosed species 2%. The prevalence was significantly higher in the period from June to October (3.2 < odds ratio [OR] <1.8, P < 0.0002) and was significantly associated with abattoir (OR < 2.8, P < 0.0001) and the length of the period the broiler houses were left empty between flocks (download period; 6 days or more) (OR = 1.6, P < 0.0198). No association between Campylobacter colonization and the age at slaughter was found. Separating the flocks into batches for slaughter elevated the flock prevalence from 0.41 after the first batch had been slaughtered to 0.46 after all batches had been slaughtered. PMID- 11195661 TI - Suicide among gay and lesbian adolescents and young adults: a review of the literature. AB - This paper explores the issue of suicide among gay and lesbian adolescents and young adults, as well as provides information to guide clinicians in working effectively with this population. The theoretical perspectives on homosexual identity development by Troiden, Cass, and Lewis are discussed in connection with Durkheim's Suicide Theory and various theoretical risk factors, as well as implications for social work practice. This paper is intended to be utilized as a tool during the assessment phase of treatment with an adolescent or young adult who may be questioning his or her sexuality. PMID- 11195662 TI - Museums, friends, and lovers in the New South: Laura's Web, 1909-1931. AB - Laura Bragg, a member of the first graduating class at Simmons College, journeyed to Charleston as a New Woman in 1909. As the first woman director of a major scientific museum in the United States, Bragg transformed the Charleston Museum into a public education institution and became an innovative leader in museum education. This article documents Bragg's contributions within the context of antebellum culture where the Southern Belle was placed on a Victorian pedestal and Boston marriages were an unknown phenomenon. Using extensive and hitherto unpublished correspondence, the authors detail Bragg's lesbian relationships and describe her network within the homosexual male community during the era of the Charleston Renaissance. PMID- 11195663 TI - Recent scholarship on homosexuality in the Greco-Roman world. PMID- 11195664 TI - GLBT campuslife on the Web. PMID- 11195665 TI - What is the Word at Logos College? Homosocial ritual or homosexual denial in Don Delillo's End Zone? AB - "What Is the Word at Logos College? Homosocial Ritual or Homosexual Denial in Don Delillo's End Zone?" investigates the homoerotic desire that, despite being culturally repressed, periodically surfaces in foothall. Given the highly closeted nature of American foothall, it is necessary to look at the puns, allusions, and interactions between the players to see how Don DeLillo has created a text that subtly exposes the homoerotics of male sport. In order to strengthen the connection between homoeroticism and football, I will show how football's invention and organization in America coincides with the construction of the homosexual subject. Football and other arenas for male-male play become enforced at the same time as desire begins to express itself; thus, football is the logical place in America to look for unresolved (and resolved) male homosexuality, and DeLillo does this skillfully. PMID- 11195666 TI - The evolution of homoerotic behavior in humans. AB - This paper presents a theoretical model for the evolution of same-sex sexual behavior, or homoerotic behavior, in humans. Contrary to the traditional study of the topic, the emphasis is on homoerotic behavior itself, irrespective of sexual orientation. It is an inferential model drawn from cross-species evidence, cross cultural evidence, and current evolutionary theory. It is posited that humans evolved a disposition for homoerotic behavior because it increased same-sex affiliation among peripheralized hominids and indirectly influenced rates of survival and reproductive success. The implications for the conceptualization of same-sex sexual behavior and future research are indicated. PMID- 11195667 TI - The romantic sexology of John Addington Symonds. AB - This paper examines a radical text by the English Classicist and homosexual, John Addington Symonds (1840-1893). Through a close study of an unpublished and long concealed manuscript, "A Problem in Modern Ethics" (1891), Symonds's political vision and the odd form of writing it takes is revealed as romantic in character. Symonds polemicizes against the pathologization of homosexuals in the legal medical discourses of the time and advocates on behalf of a latent homosexual ethics, shunned from modern Western society, but continuing to hold forth a promise for the civic and moral renewal of Western countries. Against the positions of Krafft-Ebing and others, Symonds argues for the acceptance of "manly love," in the spirit of the ancients, as a source of moral inspiration for a declining Europe. Where Symonds is often read by historians of homosexual radicalism as a precursor to the radical tradition of the 20th century, romantic acceptance of the untimeliness of his moral vision, indicates less a politically progressive than a romantically fatalistic enterprise. PMID- 11195668 TI - [Puncture-drainage sanation of abdominal abscesses: is it sufficient treatment?]. AB - Some anatomical grounds of postoperative extravisceral abscess formation, methods and results of their treatment, therapeutic policy in abscesses of parenchymatous organs are presented. 681 patients with abdominal abscess of various location were examined. Detailed analysis of ultrasonic and computed tomographic semiotics of postoperative extravisceral suppurative focus was carried out in 164 patients. The risk zones of extravisceral abscess formation in the conditions of changed visceral syntopy and destroyed ligamentic structures were determined. The efficiency of puncture-drainage treatment in different variants of subdiaphragmatic abscess was 89.4%, in abscess of omental bursa--83.3%. Intracavital prolonged proteolysis by immobilized proteinases (imosimase) was applied. The injection of imosimase in abscess cavity led to its content lysis, including the thick products of inflammation, improving their secretion through the drainage. In the majority of the patients, the puncture-drainage treatment of abscesses of various etiology and pathogenesis is an adequate method of sanation. PMID- 11195670 TI - [Laparoscopic cholecystectomy]. AB - The results of more than 1000 laparoscopic cholecystectomies are analyzed. Significant improvement of main parameters (mean hospital stay, postoperative lethality, postoperative complications rate) is demonstrated, including cases of acute destructive cholecystitis. The conception of emergency laparoscopic cholecystectomy is proposed. It is shown that the percentage of severe complications and lethality are significantly lower in laparoscopic operations than in the open operations. The widespread opinion of frequent damage of extrahepatic bile ducts is not confirmed. The development of laparoscopic surgery justifies more active policy in acute cholecystitis. PMID- 11195669 TI - [Role of prolonged intraarterial catheter therapy in general peritonitis]. AB - The analyses of treatment results in 82 patients with general purulent peritonitis are presented. In these patients long-term intraarterial catheter therapy (IACT) was included in the complex of postoperative treatment after elimination of infection source. Postoperative peritonitis was in 66 patients, 52 patients of them underwent reoperations for persisting general peritonitis. Use of IACT promoted arrest of abdominal inflammatory process and polyorganic insufficiency due to high concentration of antibiotics in the affection focus, improvement of regional circulation, reduced number of postoperative complications and a sharp fall of lethality of 8.5%. PMID- 11195671 TI - [Gastrostomy as a stage of esophagoplasty]. AB - The description of a modified technique of gastrostoma formation on small flexure is presented. Indications for this operation in patients with tumor and cicatrical esophageal strictures, planned for gastric esophagoplasty are formulated. The are authors regard a correctly created gastrostoma as the first stage of esophagoplasty. The main mistakes in gastrostoma creation that donTt permit to use the stomach for esophagus replacement are noted. The main principles and techniques of stoma creation on small flexure are described. The presented method is recommended for use in specialized esophageal departments and in general surgical hospitals. PMID- 11195672 TI - [Laparoscopy in diagnosis and treatment of acute abdominal diseases in children]. AB - 2765 children with abdominal pains were observed in the clinic of pediatric surgery from 1995 to 1999. During the observation period the abdominal pains persisted in 85 children. As it was not possible to resect the acute abdominal diseases, these children underwent diagnostic laparoscopy. Destructive changes in the appendix were revealed in 12 patients, 73 patients have avoided unnecessary laparotomy and appendectomy. It is concluded that diagnostic potential of laparoscopy is not inferior to diagnostic laparotomy. Moreover laparoscopy has advantage as a method of final diagnosis. PMID- 11195673 TI - [Treatment of giant postoperative hernias]. AB - Modified hernial ring plasty leading to significant improvement of treatment result was used in 48 patients. Lethality was 2.1%, suppuration of the postoperative wound was seen in 16.6% patients. There was the relapse (in 3-5 years) in 9% patients. Positive result of the above method compared with other Sapezhko's plasty modifications is explained by good blood supply in sutured tissues due to absence of their excessive tension, by location of the sutures between peritoneal layers and contact of similar tissues as a result of tamponade of space between displaced flaps of scar tissues and internal sutures with duplication of fibrous tissue layer. PMID- 11195674 TI - [Transpubic approach in radical prostatectomy]. AB - Surgical interventions in prostate apex and urethral membranous part are difficult because these structures are in the depth of the small pelvis. Transpubic approach permits easy manipulations in this area. There are the following variants of this approach: symphysotomy, pubectomy, resection of superior horizontal rami of pubic bones, resection of inferior horizontal rami of pubic bones, clinoid resection of pubic bones. The simplicity, adequacy and convenience of different surgical manipulations are the advantages of transpubic approach. The clinoid resection of pubic bones is the optimal variant of this approach. In provides an adequate approach to operated organs, the integrity of pelvic ring is saved, as a result of which there are no severe orthopedic disorders in the nearest and remote postoperative periods. For determination of indications to transpubic approach, the comparative study of the transpubic and low-median approaches in radical prostatectomy was carried out in 50 male cadavers according to parameters proposed by Sozon-Yaroshevich in 1954. The type of constitution, height of symphysis, size and shape of the prostate puboprostatic ligaments, adhesion of ligaments to prostate, prostate position against symphysis, size of small pelvis venous vessels were taken into account. It was established that the angle of surgical action in wound in low-medium approach was 35-50 degrees, in transpubic approach--by 25-30 degrees more. Incline angle of surgical manipulation axis, which reflect the correspondence of surgical section to exposed organ's disposition, is very important in case of organ's immobile position. This angle in low-medium approach was 40 +/- 5 degrees, in transpubic--80-90 degrees. Dorsal venous plexus and urethrals membranous part are approachable if the prostate size is small, but if the prostate volume is more than 30 cm3 and symphysis is high (> 7 cm), it is very difficult to manipulate in this zone in low-medium approach. Transpubic approach warrants thorough and careful prostatectomy. Methods leading to disturbance of pelvic ring integrity (symphysotomy, pubectomy) have no advantages. Clinoid resection ensures the optimum view of operative field and satisfy the main requirements of surgical approach. PMID- 11195675 TI - [Ultrasonic diagnosis of complications after bypass operations in lower extremities arteries]. AB - After reconstructive vascular operations the patients need dynamic control and non-invasive monitoring. The purpose of the study was to reveal the potential of duplex scanning (DS) in assessment of bypasses function and diagnosis of postoperative complications. 148 patients after aorto-femoral and femoro popliteal bypass, including patients with late postoperative complications (shunt thrombosis, stenosis or spurious aneurysm of anastomosis) were examined. Energy colored DS was performed in scans "Toshiba" SSH-140 and "Acuson" Sequoia-512. In ultrasonic diagnosis the vascular graft was imaged as a tube structure with hyperechogenic walls and distinct pulse; it was easy to detect the material of vascular graft. In examination of distal anastomosis the initial portions of efferent arteries were usually imaged distinctly. In satisfactory distal vascular bed, the shunt's blood flow did not differ from normal blood flow. In patients with multifocal lesions the spectrum of shunt's blood flow was similar to main changed blood flow. Substantial change of blood velocity was revealed in complications (aneurysm or stenosis of anastomosis). Spurious aneurysm was imaged as a hypoechogenic pulsating formation. Thrombotic masses in aneurysm's cavity were distinctly detected at DS, unlike at angiography. In case of anastomosis insufficiency, the suture's disrupted filaments and free branch's ends could be imaged. Stenosis of anastomosis was characterized by visible lumen's stenosis, local thickening and unevenness of wall, spectrum's change and blood velocity increase. In shunt's thrombosis the DS permitted to follow the thrombed graft's path, to reveal the cause of thrombosis and to detect the condition of outflow tract. The authors regard DS as a method of choice in dynamic control for state of bypasses and arteries in patients after reconstructive operations in lower extremities arteries. PMID- 11195677 TI - [Atypical approach with allogenous vein for hemodialysis]. PMID- 11195676 TI - [Opportunity of operative traumatism decrease in patients with complicated tricuspid valve defect]. AB - This study examined the results of surgical trivalve of 44 patients with trivalve heart defect. In all the patients the heart defect was combined with two and more complicating factors: advanced III-degree calcinosis of the valves, cardiomegaly, cardiac fibrillation, left atrium thrombosis, high pulmonary hypertension. In 20 patients the operative intervention on the heart was repeated. The analysis of the results allowed to recommend some surgical techniques which allowed to decrease surgical traumatism in patients with complicated trivalve heart defect. Low traumatism was possible because of incomplete removal of the calcium masses extending on the fibrotic ring and outside, use of two-row counter U-suture on linings for the prosthesis fixing, transdoubleatrial approach without isolation of the heart from the adhesions in dense pericardial obliteration, correction even insignificant trivalve heart defect or relative valve incompetence. PMID- 11195678 TI - [Right-sided hemihepatectomy for hepatic abscess complicated by recurrent profuse bleeding]. PMID- 11195679 TI - [Use of electrographic method for detection of catheter position in the aorta]. AB - Electrographic method has permitted to detect the position of aorta catheter's end in 5 patients. This method is most available for intensive care departments of city hospital, because it doesn't require special equipment and additional staff, is easy to master, may be directly used during catheterisation, is safe for patients and staff and is cost effective. PMID- 11195680 TI - [Intraoperative ultrasonic examination in diagnosis of surgical diseases]. PMID- 11195681 TI - [Efficacy of obesity surgical treatment in diabetes mellitus type II]. PMID- 11195682 TI - [Endobronchial laser therapy in the preoperative preparation of patients with lungs surgical diseases]. PMID- 11195683 TI - [Clinical variants and treatment of gastrointestinal fistulas]. AB - The experience of 411 patients treatment, aged from 15 to 78 years with gastrointestinal tract fistulas are summarized. Depending on clinico-anatomical picture, fistulas are divided in 5 types. There were 110 (26.8%) patients with fistula type I, 36 (8.7%)--type II, 70 (17.03%)--type III, 29 (7.5%)--type IV, 66 (40.4%)--type V. Treatment policy was developed for each group. Necessity of urgent relaparotomy in patients with fistula type I, early relaparotomy in fistula type II, late relaparotomy and elective operations in fistula types III, IV and V were substantiated. At usage of this treatment 102 (24.8%) from 411 patients died. PMID- 11195684 TI - Recreational pharmaceuticals. PMID- 11195685 TI - Your A to Z guide to the year in medicine. PMID- 11195686 TI - Don't pass the salt. PMID- 11195687 TI - Buzzing about safety. The latest studies say there is no cell-phone risk, but many users are making their own decisions about taking precautions. PMID- 11195688 TI - Lost on the campus. PMID- 11195689 TI - The future of drugs. PMID- 11195690 TI - Brave new pharmacy. PMID- 11195691 TI - AIDS. Still no vaccine, but better antiviral drugs are on the way. PMID- 11195692 TI - Cancer. Smart bombs for targeting deadly tumors. PMID- 11195693 TI - Mental illness. Probing the chemistry of the brain. PMID- 11195694 TI - Autoimmune diseases. New ways to intervene when the body attacks itself. PMID- 11195695 TI - Obesity. Healthy genes could mean smaller jeans. PMID- 11195696 TI - Alzheimer's disease. New insights into its cause lead to new drug strategies. PMID- 11195697 TI - Heart disease. Rethinking treatments for the heart. PMID- 11195698 TI - Parkinson's disease. Lubricating gummed-up brains. PMID- 11195699 TI - The antibiotics crisis. We're in the midst of an escalating arms race with the microbe, and we may be losing. PMID- 11195700 TI - Beyond needles and pills. Drug reactions kill tens of thousands of patients each year. Part of the problem is how the medicine is being delivered. PMID- 11195701 TI - Potions from poisons. PMID- 11195702 TI - [SSRI antidepressants and alcoholism]. AB - It seems that SSRI (moreover than being antidepressant) may reduce alcohol consumption by decreasing desire, craving and liking for alcohol. The 5-HT reuptake inhibitors may be helpful for the treatment of alcoholism by reducing relapse frequency and severity. Moreover, if depression or anxiety is present, it should be effective to give them immediately because of the frequent association between these pathologies and alcoholism. PMID- 11195703 TI - [How I investigate...a burning mouth]. AB - Burning mouth is a symptom typical for the oral mucosa. In contrast, pruritus is absent at this site. The situation which is the reverse on the skin can be explained by microanatomical differences in the sensorial innervation and by a different balance between neuromediators. Burning mouth sensation calls for the search of a series of diseases. However, it is most often a monosymptomatic expression of a minimal lichenoid stomatitis. PMID- 11195704 TI - [Pharma-clinics. The drug of the month. Levofloxacin (Tavanic)]. AB - Levofloxacin, the (-)-(S)-enantiomer isolated from the racemate ofloxacin, is launched by Aventis under the trade name of Tavanic. This new oral and parenteral antibiotic belongs to the fluoroquinolone family and exerts a bactericidal activity upon a large spectrum of microorganisms, including Gram negative and Gram positive bacilli (among which Streptococcus pneunomiae), and atypical respiratory pathogens. It also has interesting pharmacokinetic properties. Besides the classical indications of other fluoroquinolones (especially complicated urinary tract infections, including pyelonephritis, and severe skin and soft tissue infections), levofloxacin is indicated for the treatment of acute sinusitis, acute exacerbations of chronic bronchitis and community-acquired pneumonia. PMID- 11195705 TI - [Info-congress. COPERNICUS and Val-HEFT studies]. PMID- 11195706 TI - [Image of the month. Malignant fibrous histiocytoma]. PMID- 11195707 TI - [How I treat... refractory multiple myeloma with thalidomide]. AB - Despite the use of high-dose chemotherapy with autologous hematopoietic stem cell transplantation, multiple myeloma remains largely uncurable. Indeed complete remission rate is about 50% and median survival reaches 5 years without plateau. Recently thalidomide has been identified as a promising agent. We report the clinical story of 2 patients with refractory myeloma that we treated successfully with thalidomide. PMID- 11195708 TI - [Clinical case of the month. Disseminated fusariosis in a immunocompromised patient]. AB - Fusarium spp are ubiquitous soil saprophytes and occasional plant pathogens. Fusariosis in humans is usually limited to superficial mycoses. We report the case of a disseminated fungal infection due to Fusarium spp in an immunosuppressed patient suffering from acute lymphoblastic leukemia. This report and review of the recent literature suggest that Fusarium spp are emerging fungal pathogens in immunosuppressed patients. PMID- 11195709 TI - [Primary hyperparathyroidism: etiology, diagnosis and treatment]. AB - Primary hyperparathyroidism is a not so infrequent disease that is often overlooked by physicians. Its incidence is estimated to be about 28 in 100.000 subjects, mainly women over seventy years old. Three to four percents of women over seventy are affected. Hyperparathyroidism can be isolated or be a component of a more complex syndrome like multiple endocrine neoplasms (MEN). Patients can be asymptomatic or present with symptoms like asthenia, hypertension or nephrolithiasis. The biological investigation requires the combined measurements of plasmatic ionized calcium and parathormone. In some cases, more specific explorations like calcium loading tests have to be performed in order to confirm the diagnosis. PMID- 11195710 TI - [Idiopathic pulmonary fibrosis: a new histopathologic classification and clinical aspects]. AB - Idiopathic pulmonary fibrosis (IPF) comprises different interstitial lung diseases of unknown origin. They are classified into four groups based on pathologic criteria: UIP, DIP, AIP and NSIP. This classification helps in terms of prognosis and treatment. In addition to history, physical examination and common investigations (chest X ray, pulmonary function testing), a bronchoalveolar lavage (BAL), a high-resolution CT scan and ideally a open-lung biopsy are needed to establish a precise diagnosis. The patients are usually treated by immunosuppressive agents, and mainly by corticoids. However, in UIP, lung transplantation is the only way to improve survival. PMID- 11195711 TI - [Fibromyalgia in the year 2000]. AB - Musculoskeletal pain is common in the population. Several pathologies like fibromyalgia (FM), chronic fatigue syndrome (CFS) or spasmophilia are associated with functional myalgia. The etiology of FM remains elusive, but the diagnosis is well established. The criteria for the classification are widespread pain combined with tenderness at 11 or more of the 18 specific tender points sites. The prevalence is 2% in the general population. This article reviews recent data on the pathophysiology and treatment of FM. PMID- 11195712 TI - [Urban and rural mycozoonoses]. AB - The main mycozoonoses are due to specific dermatophytes which are pathogens for man and animals. Contamination occurs most often after close contact with the animal showing clinical lesions or with inapparent carriage only. The contaminated environment also participates to the mycozoonotic epidemics. Interhuman transmission is more rarely encountered. Young children before puberty are most receptive to the disease. The main urban mycozoonosis is due to Microsporum canis transmitted by dogs and cats. Rural mycozoonoses due to Trichophyton ochraceum can be contracted from bovines. Zoophilic dermatophytes induce lesions which are most often quite inflammatory in humans. PMID- 11195713 TI - Information processing during sleep onset and sleep. AB - This Special Section examines the extent of information processing during sleep onset and sleep itself. It is generally agreed that, stimulus input is markedly inhibited during sleep, thus preventing conscious awareness of the external environment. Overt behavioural responses are rarely made within sleep. Two neurophysiological measures are therefore often used. The electrical activity of the brain (the EEG) can be employed to distinguish waking (conscious) from sleeping (unconscious) states. It is also possible to quantify the EEG prior to and following a detection (or a failure of a detection) of a stimulus. Such measures can thus be used to predict conscious awareness. A second measure that frequently has been employed is the brain's response to an external stimulus (the evoked potential). Different components of the evoked potential can be used to trace the extent of information processing during the different states of consciousness. Some are associated with a preconscious detection while others are associated with conscious awareness. Other evoked potentials may be unique to sleep. PMID- 11195714 TI - The mismatch negativity to frequency deviants during the transition from wakefulness to sleep. AB - This study examines the changes in the Mismatch Negativity during the transition from a waking, conscious state to one of sleep and unconsciousness. Auditory event-related potentials were recorded from eight participants during the sleep onset period. A 1,000 Hz-standard stimulus was presented every 600 ms. At random, on 20% of the trials, the standard was changed to either a large 2,000-Hz or a small 1,100-Hz deviant. During wakefulness, the large deviant elicited a larger, long-lasting MMN than the small deviant. Following the large deviant during relaxed wakefulness and Stage 2 sleep, the MMN continued to be elicited although it was reduced in amplitude. No significant MMN was recorded for either deviant in Stages 1 and slow wave sleep. The loss of consciousness therefore appears to have a marked effect on the MMN. PMID- 11195715 TI - The impact of prestimulus EEG frequency on auditory evoked potentials during sleep onset. AB - Auditory evoked potentials were recorded during wakefulness, Stage 1, and Stage 2 non-REM sleep using a three-tone auditory oddball paradigm. Stage 1 sleep was divided into trials preceded by alpha and those preceded by theta. A negative wave peaking at about 100 ms, N1, displayed a significant decrease in amplitude with the onset of Stage 2 sleep. A later N2 peaked at about 250 ms in the waking state. This changed into a sleep-specific negative wave peaking at 300 ms (N300) at the alpha-theta transition within Stage 1. The P300 displayed a similar shift to become a P450 in Stage 2 sleep. N550 was specific to Stage 2, and was larger in response to rare, rather than frequent stimuli. There was no evidence of any enhancement to relevant rare stimuli compared with irrelevant rare stimuli. PMID- 11195716 TI - EEG characteristics prior to and following the evoked K-Complex. AB - This study was designed to determine if the K-Complex reflects an arousal from sleep or a sleep protection mechanism. Ten participants were presented auditory stimuli every 20 s while asleep. Trials were sorted according to the presence or absence of a K-Complex. A fast Fourier Transformation of the data was computed on EEG segments prior to and following stimulus onset. The log power of activity in delta, theta, alpha, sigma, and beta bandwidths was computed. When a K-Complex was elicited, there were no differences in EEG activity prior to and following the stimulus. However, during slow wave sleep, when a K-Complex was not elicited, there was a significant overall increase in theta, alpha, sigma, and beta activity following stimulus. These results tend to support the notion that the K Complex appears to prevent arousal. PMID- 11195717 TI - Awareness during drowsiness: dynamics and electrophysiological correlates. AB - During drowsy periods, performance on tasks requiring continuous attention becomes intermittent. Previously, we have reported that during drowsy periods of intermittent performance, 7 of 10 participants performing an auditory detection task exhibited episodes of non-responding lasting about 18 s (Makeig & Jung, 1996). Further, the time patterns of these episodes were repeated precisely in subsequent sessions. The 18-s cycles were accompanied by counterbalanced power changes within two frequency bands in the vertex EEG (near 4 Hz and circa 40 Hz). In the present experiment, performance patterns and concurrent EEG spectra were examined in four participants performing a continuous visuomotor compensatory tracking task in 15-20 minute bouts during a 42-hour sleep deprivation study. During periods of good performance, participants made compensatory trackball movements about twice per second, attempting to keep a target disk near a central ring. Autocorrelations of time series representing the distance of the target disk from the ring centre showed that during periods of poor performance marked near-18-s cycles in performance again appeared. There were phases of poor or absent performance accompanied by an increase in EEG power that was largest at 3 4 Hz. These studies show that in drowsy humans, opening and closing of the gates of behavioural awareness is marked not by the appearance of (12-14 Hz) sleep spindles, but by prominent EEG amplitude changes in the low theta band. Further, both EEG and behavioural changes during drowsiness often exhibit stereotyped 18-s cycles. PMID- 11195718 TI - Norms of subjective frequency of use and imagery for a sample of 1,916 French nouns. AB - Norms of rated subjective frequency of use and imagery on seven-point scales are reported for 1,916 French nouns. Subjective frequency was defined as the rated frequency of occurrence of words in spoken French, and imagery was defined as the rated case with which a word aroused a mental image. The mean, standard deviation, and percentile rank of the frequency and imagery ratings for each item are presented in the Appendix together with their objective frequency of occurrence in Baudot's (1992) dictionary. Interjudge reliability was assessed by calculating the correlation between the mean ratings of items repeated in the booklet, between the mean ratings obtained from odd-numbered and even-numbered respondents, and by computing the Cronbach alpha statistic for each page of the booklet. These reliability estimates were equal to or greater than .92 for frequency and for imagery, confirming the high level of interjudge consistency. Although the estimates provided by female and male participants were highly correlated (r = .97), the former gave a slightly higher frequency rating to the word sample but a slightly lower imagery rating than the latter did. Moreover, female respondents gave slightly more extreme ratings on the frequency and imagery scales. An analysis of the absolute difference between female and male ratings revealed a discrepancy of one half point or more on 20% of the word sample for frequency and 13% for imagery. On both scales, the mean absolute difference between male and female ratings was larger than that obtained by chance alone. This finding highlights the possibility that some words may not be equally familiar to women and men or may not evoke imagery with the same ease in these groups. Validity estimates for the frequency and imagery ratings were derived from correlations with scale values drawn from other normative studies. These correlation coefficients were equal to or greater than .78 for frequency and .86 for imagery, confirming the high level of consistency between this and other studies. An analysis of the relationship between subjective frequency and imagery ratings indicated that these variables are generally uncorrelated but exceptions occur. In the present study the coefficient of the correlation between subjective frequency and imagery was .24. However, when items with extreme mean frequency were excluded from the calculation, the correlation coefficient dropped to .04 and was no longer significant. Imagery ratings from five independent studies were all positively and significantly correlated with Vikis-Freibergs's (1974) frequency estimates, which were obtained from a free-association task. This finding suggests that word association, as a form of cued recall, may be influenced by several stimulus attributes including prior frequency of association and imagery-evoking value. The pattern of correlation between imagery ratings and text-based frequency estimates is not coherent. It reveals significant correlations only in select cases and no consistent polarity of linear relationship. The main contribution of this research is to provide reliable estimates of subjective frequency and imagery value for a word sample that is larger than those included in previous studies. A close examination of the linear relationship among the various sources of frequency and imagery data underscores the risk of confounding these variables in the selection of lexical stimuli for research. PMID- 11195719 TI - On the role of eye movements and saccade preparation in generating auditory inhibition of return. AB - In three experiments, listeners were required to either localize or identify the second of two successive sounds. The first sound (the cue) and the second sound (the target) could originate from either the same or different locations, and the interval between the onsets of the two sounds (Stimulus Onset Asynchrony, SOA) was varied. Sounds were presented out of visual range at 135 azimuth left or right. In Experiment 1, localization responses were made more quickly at 100 ms SOA when the target sounded from the same location as the cue (i.e., a facilitative effect), and at 700 ms SOA when the target and cue sounded from different locations (i.e., an inhibitory effect). In Experiments 2 and 3, listeners were required to monitor visual information presented directly in front of them at the same time as the auditory cue and target were presented behind them. These two experiments differed in that in order to perform the visual task accurately in Experiment 3, eye movements to visual stimuli were required. In both experiments, a transition from facilitation at a brief SOA to inhibition at a longer SOA was observed for the auditory task. Taken together these results suggest that location-based auditory IOR is not dependent on either eye movements or saccade programming to sound locations. PMID- 11195720 TI - Acculturation attitudes and sociocultural adjustment of sojourner youth in Israel. AB - Among 300 Jewish sojourner youth (age range: 15-18 years) from the Russian Federation, the authors investigated associations of acculturation attitudes, measures of sociocultural adjustment, and length of the encounter with the host society, Israel. All the youth were participating in a 1-3-year program of high school studies in Israel. In the light of J. W. Berry's (1997) acculturation model, the authors examined the assumptions that the participants' adjustment to Israeli society would require readiness to abandon some of their previous identity and to adopt elements of a new identity characteristic of the host society. Lower degrees of separation and higher degrees of integration were positively linked with measures of sociocultural adjustment. The adjustment scores tended to decrease over time spent in Israel. PMID- 11195721 TI - Motivation in person perception: role of the other's perspective. AB - In previous studies (G. Steins & R. A. Wicklund, 1993, 1996, 1997; R. A. Wicklund & G. Steins, 1996), perspective-taking depended on the interplay between 2 variables--(a) press (the relationship intensity between perceiver and perceived person) and (b) conflict. In the absence of conflict, perspective-taking was positively related to press; in the presence of conflict, perspective-taking was negatively related to press. In the present 3 studies, involving samples of German students, the author conducted a detailed exploration of the motivational impact of press on perspective-taking: In the 1st study, she measured press via the participant's wish to deal with the other person; in the 2nd study, via the perceiver's preoccupation with the target; and in the 3rd study, she defined press as a general tendency of some participants to become absorbed in other individuals. All 3 studies included elements of conflict. The results further supported the perspective-taking model and improved the understanding of the influence of motivation in person perception. PMID- 11195722 TI - Sensation-seeking and differentially arousing television commercials. AB - The authors predicted (a) that disinhibited consumers would react more favorably to advertising that was high in arousal and (b) that inhibited consumers would react more favorably to advertising that was low in arousal. They tested these predictions by having U.S. college students evaluate both the commercial and the product being marketed in 1 of 2 beer commercials. The prospective buyers then completed a measure of dispositional sensation-seeking tendencies. Although the participants who differed in disinhibition reacted differently to the 2 commercials, the nature of their responses was more complex than predicted. PMID- 11195723 TI - Crowding effects of density and personal space requirements among older people: the impact of self-control and social support. AB - The authors examined the effects of self-control and social support among a representative sample of 300 older people, 150 in high-density and 150 in low density households in India. The Self-Control Schedule (M. Rosenbaum, 1980), the Comfortable Interpersonal Distance Test (M. Duke & S. Nowicki, 1972), the Social Support Questionnaire, and the Judgement of Environmental Quality Scale (I. G. Sarason, H. M. Levine, R. B. Basham, & B. R. Sarason, 1983) were the measures. A 2 x 2 x 2 (Density x Social Support x Self-Control) analysis of variance for perceptions of home environment and personal space requirements revealed that the Self-Control x Social Support interaction moderated the crowding effects of density: The participants in high-density households evaluated their home environments more positively and reduced their personal space requirements. PMID- 11195724 TI - Chinese implicit leadership theory. AB - In a 1st attempt to identify an implicit theory of leadership among Chinese people, the authors developed the Chinese Implicit Leadership Scale (CILS) in Study 1. In Study 2, they administered the CILS to 622 Chinese participants from 5 occupation groups, to explore differences in perceptions of leadership. Factor analysis yielded 4 factors of leadership: Personal Morality, Goal Efficiency, Interpersonal Competence, and Versatility. Social groups differing in age, gender, education level, and occupation rated these factors. Results showed no significant gender differences, and the underlying cause for social group differences was education level. All groups gave the highest ratings to Interpersonal Competence, reflecting the enormous importance of this factor, which is consistent with Chinese collectivist values. PMID- 11195725 TI - Perceived job image among police officers in Singapore: factorial dimensions and differential effects. AB - The authors examined the perceived job image of police officers in Singapore and its differential effects on their work-related attitudes (e.g., job satisfaction, organizational commitment, and intention to quit). The authors obtained data from questionnaire surveys and focus-group interviews. Perceived job image consisted of 4 dimensions: (a) prestige, (b) integrity, (c) competence, and (d) nonroutine job nature. Results of hierarchical regression analyses suggested that the first 2 dimensions of the perceived job image construct were salient in affecting the police officers' work-related attitudes. PMID- 11195726 TI - Coping style following acute stress in competitive sport. AB - The purpose of this study was to ascertain coping styles among competitive athletes in response to various acute stressors. Specifically, the authors used a 134-item survey to measure approach and avoidance coping styles, with task focused and emotion-focused coping tendencies nested hierarchically as subdimensions under each. Australian and U.S. college-aged participants indicated the extent to which they used approach, avoidance, task-focused, and emotion focused coping strategies (a 4-factor model) in response to selected acute stressors experienced during sport competition. The authors computed confirmatory factor analysis to test the theoretically driven model. The criterion loading of .30 and above for each of the factors reduced the survey to 65 items. Findings indicated stronger links between the 2 approach constructs of task- and emotion focused coping than between the 2 avoidance constructs of those subdimensions. The goodness-of-fit indices for the 4-factor model were 0.58 and 0.57 for Australian and U.S. samples, respectively, and .71 overall. Concomitant low correlations between the 2 approach (0.18) and the 2 avoidance dimensions (0.43) reflected relatively high residuals between stressors. In general, psychometric analyses suggest that coping style may be more prevalent in some situations than others, lending partial support for the transactional model of coping. PMID- 11195727 TI - Affectionate same-sex touch: the influence of homophobia on observers' perceptions. AB - The author extended the proposition (V. J. Derlega, R. J. Lewis, S. Harrison, B. A. Winstead, & R. Costanza, 1989) that the fear of being seen as homosexual accounts for the common finding that U.S. women engage in more same-sex touch than do U.S. men. The author proposed a theoretic model positing that the magnitude of homophobia's influence on behavior and on reactions to behavior is proportional to the likelihood that the behavior is sexual in nature. An experiment involving reactions to same-sex embraces demonstrated that, although homophobia was negatively related to evaluations of same-sex affectionate touch, the magnitude of the relationship covaried with the probability that the touch was sexual. The implications of these findings for longer range theory development are discussed. PMID- 11195728 TI - Education and career aspirations of Palestinian and U.S. youth. PMID- 11195729 TI - Management of abdominal pain. PMID- 11195730 TI - Clinical aspects of recurrent abdominal pain. PMID- 11195731 TI - The role of motility in functional abdominal disorders in children. PMID- 11195732 TI - Biopsychosocial issues in functional abdominal pain. PMID- 11195733 TI - Gastroesophageal reflux and other causes of abdominal pain. PMID- 11195734 TI - Chronic abdominal pain: inflammatory bowel disease and eosinophilic gastroenteropathy. PMID- 11195735 TI - Management of abdominal pain. Resident's column. PMID- 11195736 TI - A fictitious case of runaway abdominal pain. PMID- 11195737 TI - Laser pneumatic retinopexy for repair of recurrent retinal detachment after failed scleral buckle--ten years experience. AB - BACKGROUND: Although pneumatic retinopexy was introduced for the repair of primary retinal detachments, we have had excellent long-term success in employing this technique along with laser photocoagulation following failure of routine scleral buckle surgery in nonvitrectomized eyes over the last 10 years. PATIENTS AND METHODS: We categorized a consecutive series of 40 eyes that failed primary scleral buckling surgery and had at least six months follow-up. Eyes were separated into two groups: those with 1) subretinal fluid persisting or developing during the first 14 days after surgery or 2) those accumulating subretinal fluid at least 14 days after initially successful anatomic reattachment of the retina. RESULTS: In these groups, 36 of the 40 eyes (90%) were successfully reattached using outpatient pneumatic retinopexy alone. Complications were limited to the production of new retinal breaks in 5 patients. The 4 pneumatic retinopexy failures were all subsequently treated successfully with either scleral buckle revision or vitrectomy. CONCLUSION: We believe that laser pneumatic retinopexy repair of recurrent retinal detachments following scleral buckle and without significant proliferation vitreoretinopathy (PVR) should be considered ahead of conventional surgical intraoperative techniques. Laser pneumatic retinopexy may be a very successful procedure for the treatment of recurrent retinal detachments after failed scleral buckle surgery. In a consecutive series of 40 eyes with recurrent retinal detachment, we were able to repair 36 with pneumatic retinopexy alone. PMID- 11195738 TI - Iris neovascularization after vitrectomy combined with phacoemulsification and intraocular lens implantation for proliferative diabetic retinopathy. AB - PURPOSE: To analyze the incidence of iris neovascularization after vitrectomy combined with phacoemulsification and intraocular lens (IOL) implantation using a small incision in the treatment of proliferative diabetic retinopathy (PDR). PATIENTS AND METHODS: We studied a consecutive series of 46 eyes in which vitrectomy combined with phacoemulsification and IOL implantation had been performed, and compared the surgical results with a prior series of 40 eyes in which vitrectomy alone had been performed. RESULTS: Postoperative iris and angle neovascularization was found in 6 eyes (15%) treated by vitrectomy alone, but in only 1 eye (2%) treated by combined vitrectomy (P<0.05). Final visual acuity improved by two or more lines in 23 eyes (57%) in the vitrectomy alone group, and in 35 eyes (76%) in the combined vitrectomy group. CONCLUSIONS: The incidence of postoperative rubeosis iridis was significantly lower, and the visual results were satisfactory with vitrectomy combined with phacoemulsification and IOL implantation for PDR. These findings suggest that combined vitrectomy for PDR is a useful surgical procedure. PMID- 11195739 TI - Ocular penetration of cefepime following systemic administration in humans. AB - OBJECTIVE: To investigate the penetration of cefepime (a fourth generation cephalosporin) into the aqueous humor after single-dose intravenous administration in humans. PATIENTS AND METHODS: Before receiving cataract surgery, 30 patients received randomly 1 g (group 1, 15 patients) and 2 g (group 2, 15 patients) single intravenous injection of cefepime before surgery. Samples of aqueous humor and serum were obtained at 0.5, 1, 2, 4, and 12 hours after injection. Three patients were sampled each time for 1 g and 2 g of cefepime. Samples were assayed for cefepime concentrations with high performance liquid chromatography (HPLC). RESULTS: All the patients had detectable cefepime in their aqueous humor and serum measurable by HPLC. A mean peak aqueous humor level was 5.16 +/- 0.88 microg/mL in group 1 and 5.87 +/- 1.64 microg/mL in group 2 at 0.5 hour after injection. The mean level of cefepime in aqueous humor decreased after 0.5-hour measurements in both groups and was measured as 0.82 +/- 0.21 microg/mL in group 1 and 2.04 +/- 0.30 microg/mL in group 2 at 12 hours after injection. CONCLUSION: Aqueous humor levels of cefepime after single IV injection were above the minimum inhibitory concentration (MIC90) for most ocular pathogens, but the duration of exposure to an antibiotic was not sufficient for therapeutic effect. PMID- 11195740 TI - Excimer laser photorefractive keratectomy for hyperopia. AB - BACKGROUND AND OBJECTIVE: Photorefractive keratectomy (PRK) has been extensively evaluated for the correction of myopia. This study was undertaken to assess the safety, efficacy, and reliability of PRK in the correction of hyperopia. PATIENTS AND METHODS: There were 28 eyes with refractions of +1 to +7.75 D treated for hyperopia with the Chiron Technolas 217-C excimer laser. Thorough visual assessments were made before treatment and at regular follow-up to 18 months. Complications and patient satisfaction were noted. RESULTS: At 18 months the mean subjective refraction was +0.46+/-1.00 D with 26 eyes (92.8%) within 1 D of emmetropia. Thirteen eyes (46.4%) achieved uncorrected visual acuity (UCVA) of 20/20 or better and all patients had an UCVA of > or = 20/32 or better. Best corrected visual acuity (BCVA) remained unchanged in 26 eyes (92.8%) and improved in 2 eyes (7.2%). On the seventh day from treatment, 17 eyes (25%) had a loss of 2 or more lines of BCVA. At 15 days this was reduced to 8 eyes (14.3%) and at one month to 3 eyes (3.6%). There were no cases of loss of 2 or more lines of BCVA at 18 months of follow-up. All patients expressed a high degree of satisfaction. CONCLUSIONS: Photorefractive keratectomy safely and effectively reduced hyperopia in the patients studied. The technique was reliable and still offered good results at 18 months of follow-up. PMID- 11195741 TI - The effect of pterygium surgery on corneal topography. AB - OBJECTIVE: The aim of this prospective randomized clinical study was to evaluate the effect of pterygium surgery on the corneal topography using a computerized corneal topography system. PATIENTS AND METHODS: Computerized corneal topography was performed on 27 patients with primary pterygium before and after pterygium excision surgery. The topographical changes that occurred following surgery were evaluated using paired and unpaired two-tailed t-test and Pearson coefficient of correlation analyses. Simulated keratometric astigmatism at the central 3 mm and the total mean refractive powers of the whole cornea were measured before and after surgery. Following surgery, flattened or steepened corneal areas were determined. RESULTS: Simulated keratometric astigmatism at 3 mm was found to be 2.30 +/- 2.08 D (0.2 - 7.63) preoperatively and 0.82 +/- 0.74 D (0.06 - 2.79) postoperatively. The difference between these two values was statistically significant (t = -3.46, P = 0.002). Total mean refractive power of the whole cornea was found to be 42.26 +/- 0.63 (40.80 - 43.64) preoperatively and 43.69 +/ 0.88 (41.50 - 44.90) postoperatively and the difference was 1.42 +/- 0.87. There was a statistically significant high difference (t = 28.36, P < 0.001). When preoperative and postoperative corneal topographies were compared, the whole cornea was found steeper at the postoperative period except a little region in the superior nasal quadrant. CONCLUSION: We believe that corneal topographical changes caused by the pterygium are almost reversible after surgical treatment, and postoperatively the cornea becomes steeper. PMID- 11195742 TI - Fat-conserving aesthetic lower blepharoplasty. AB - OBJECTIVE: To evaluate a variation on lower eyelid fat-conserving blepharoplasty as a treatment for several facets of periorbital aging, especially eyelid fat protrusion and skeletonization of the inferior orbital rim. PATIENTS AND METHODS: Retrospective review of 14 consecutive patients at an academic center who underwent fat-conserving lower blepharoplasty over an 8-month period. Independent evaluation of surgical success was performed by two experienced surgeons. RESULTS: Fat-conserving blepharoplasty corrected skeletonization of the inferior orbital rim in 13 of 14 cases, and was moderately effective at correction of lower eyelid fat protrusion and wrinkles. There were no complications. CONCLUSION: Fat-conserving lower blepharoplasty is a safe and effective surgical technique for reduction of visibility of the bony orbital rim and can complement other procedures used to improve signs of aging in the periorbital region. PMID- 11195743 TI - The treatment of lacrimal apparatus obstruction with the use of an inner canthal Jones tube insertion via a transcaruncular route. AB - BACKGROUND AND OBJECTIVE: To evaluate the clinical utility of the lacrimal bypass surgery using Bowman's probe in treatment of obstruction of the lacrimal apparatus. PATIENTS AND METHODS: This study evaluated 124 cases of obstruction of the lacrimal passage systems with mean epiphora of 2.7 years. An incision was made on the side of the caruncle, and the lacrimal bone was penetrated between the lacrimal sac and the nasal mucosa by Bowman #0. Insertion of a Jones tube was made at the new lacrimal pathway, a puctum dilator or scissors was introduced through the caruncle and dilated across the lacrimal bone into the nasal cavity. The Jones tube was introduced over the probe into the nasal cavity, and fixed at the caruncle with nonabsorbable suture material. RESULTS: Complete resolution of epiphora was accomplished in 120 (96.8%) of 124 eyes; only 4 (3.2%) eyes failed during a mean of 17.1 months of follow-up. CONCLUSION: This procedure is simple and safe with no facial scarring, short operation time, high success rate, and can be performed under local anesthesia. Therefore, the clinical utility of this procedure seems to be of value in treatment of complicated obstruction of the lacrimal apparatus. PMID- 11195744 TI - Quantitative analysis of hydroxyl radicals in the anterior optic nerve of the cat following transient ischemia. AB - PURPOSE: Ischemic insults in the optic nerve are relatively common ocular disorders. This study provides quantitative data on the generation of hydroxyl radicals in the anterior optic nerve of the cat during the early reperfusion phase following 90 minutes of ischemia. MATERIALS AND METHODS: Cats were injected intravenously with sodium salicylate that by acting as an hydroxyl radical trap, forms 2,3-dihydroxybenzoic acid (2,3-DHBA). Ischemia was achieved by intraocular pressure (IOP) elevation via cannulation of the anterior chamber. Ischemia was maintained for 60 minutes in 6 eyes and 90 minutes in 12 eyes, followed by 5 minutes of reperfusion. In an additional 6 eyes, ischemia was maintained for 90 minutes without reperfusion. RESULTS: After 90 minutes of ischemia and reperfusion, mean normalized levels of 2,3-DHBA (ie, ng 2,3-DHBA/microg salicylate/mg protein) that represent the levels of hydroxyl radicals were 2.47 times (at least) higher in the anterior optic nerves than in the fellow sham operated controls (P = 0.03). These levels were 3.9 times (at least) greater than in the corresponding levels after 90 minutes of ischemia without reperfusion (P= 0.005). CONCLUSION: This study provides a quantitative analysis and evidence for the generation of hydroxyl radicals in the optic nerve of the cat following transient ischemia. A quantitative analysis may provide an important tool to detect even relatively small levels of free radicals in the tissues, and to evaluate the relative efficacy of various therapeutic agents in the inhibition of free radical generation following ischemia and reperfusion. PMID- 11195745 TI - Diode laser photocoagulation for retinopathy of prematurity: a histopathologic study. AB - Laser photocoagulation has largely supplanted cryotherapy as an effective treatment for retinopathy of prematurity. This case describes the ocular histopathologic findings of a pair of eyes in a severely premature male infant treated with diode laser photocoagulation for bilateral stage 3 retinopathy of prematurity (ROP) for 360 degrees in zone 1 with severe plus disease. The right eye responded to treatment; the left eye developed persistent vitreous hemorrhage and total retinal detachment. The histopathologic examination of laser burns in the right eye disclosed segmental areas of chorioretinal scarring with retinal atrophy and gliosis, loss of RPE and extensive atrophy of the choroid and its vasculature, which involved both the choriocapillaris and larger vessels. The left eye had iris neovascularization, a chronic organized vitreous hemorrhage and a totally detached retina. The histopathologic findings in an eye of a premature infant with threshold ROP treated with diode laser photocoagulation resembled those reported after transsceral cryotherapy. Diode laser photocoagulation may produce less severe chorioretinal damage. PMID- 11195746 TI - Progressive outer retinal necrosis in a patient with nephrotic syndrome. AB - Progressive outer retinal necrosis syndrome (PORN) is a variant of necrotizing herpetic retinopathy and the majority of the described cases were related to acquired immunodeficiency syndrome. We present a patient who is HIV negative with nephrotic syndrome and prednisolone use for 4 months who showed clinical features of PORN. Low CD4 counts and lymphocytopenia suggested immunosuppression. In the left eye, tractional retinal detachment at the posterior pole followed by incomplete posterior vitreous detachment developed. In addition to intravenous administration of acyclovir, vitreous surgeries including stripping of the posterior hyaloid and silicone-oil tamponade were successfully performed to repair the retinal detachment in the left eye and to prevent it in the right eye. PMID- 11195747 TI - The effect of tissue plasminogen activator on premacular hemorrhage. AB - BACKGROUND AND OBJECTIVE: Early vitrectomy is recommended for eyes with premacular hemorrhage, which causes fibrovascular proliferation and macular traction. The purpose of this study was to investigate the therapeutic effects of tissue plasminogen activator (tPA) on premacular hemorrhage, and the clearing of hemorrhage from the macula. PATIENTS AND METHODS: The authors injected tPA (25 37.5 microg) into the vitreous cavity of 13 eyes with premacular hemorrhage. The causes of premacular hemorrhage were diabetic retinopathy in 11 eyes and traumatic injuries in 2 eyes. Prior to tPA injection, 4 eyes had complete posterior vitreous detachment (PVD) and 9 eyes had no PVD. RESULTS: After tPA injection, the hemorrhages in 10 eyes were completely absorbed. They were absorbed partially in 2 eyes and were not absorbed at all in 1 eye. Absorption of hemorrhage in the 4 eyes with complete PVD took an average of 5.5 days, and in the 6 eyes with no PVD, it took an average of 12.7 days (P=0.002). After tPA injection, visual acuity improved in 9 eyes, remained stable in 3 eyes, and worsened in 1 eye. In 5 eyes, pars plana vitrectomy (PPV) was required after tPA injection because of recurrent vitreous hemorrhage, macular traction or nonabsorbed premacular hemorrhage. CONCLUSION: TPA seems to be a good alternative method of treatment for premacular hemorrhage, especially in eyes with complete PVD. It appears to improve vision and defer the need for PPV. PMID- 11195748 TI - A traumatic macular hole secondary to a high-energy Nd:YAG laser. AB - A case is reported of a traumatic macular hole caused by a high-energy Nd:YAG laser. The initial ocular examination revealed an explosive, crater-shaped, full thickness macular hole surrounded by local edema and detachment. By the 12th day after the injury, the hole had shrunk progressively and was covered by a thin fibrin-like membrane. A thick epiretinal membrane covered the injured area 1 month after the injury. Nine months after the injury, the macular hole closed spontaneously with a partially detached epiretinal membrane. This case demonstrates one of the natural healing processes of a traumatic macular hole. Although the hole finally closed, the patient did not regain his vision because of the severe damage to the photoreceptors, retinal pigment epithelium, and choroid. PMID- 11195749 TI - Lipemia retinalis. PMID- 11195750 TI - Subconjunctival cephalosporin anaphylaxis. AB - This case describes a patient who developed a systemic anaphylactic reaction to a subconjunctival injection of cephalosporin. The patient did well, but required intensive therapy, including airway intubation. She had a history of penicillin allergy. Even 50 mg of cephalosporin antibiotic injected locally can produce a life threatening anaphylactic reaction. PMID- 11195751 TI - Quantitative CMV antigenemia correlated with ophthalmoscopic screening for CMV retinitis in AIDS patients. AB - To assess the efficacy of the cytomegalovirus (CMV) antigen test in detecting the clinical presence of CMV retinitis. A retrospective chart review was conducted on 86 HIV positive patients who underwent dilated fundus exams for CMV retinitis. All patients had a CMV antigen assay performed within three months of their retinal exam. At a level of 45, the antigen test has a sensitivity of 96% in correctly detecting CMV retinitis and a specificity of 90.2%. The negative and positive predictive values of the antigen test were 98.2% and 80%, respectively. CMV antigen blood test provides a useful screening tool in detecting the presence or absence of CMV retinitis. An antigen level less than 45 strongly suggests the absence of retinitis. PMID- 11195752 TI - A simple closed chamber technique for repair of traumatic iridodialysis in phakic eyes. AB - A surgical technique was developed for traumatic iridodialysis repair using a small partial-thickness scleral flap and a 24-gauge disposible hypodermic needle. This procedure is a "direct iridodialysis-site approach" closed chamber technique with minimal surgical trauma that can be used in phakic, pseudophakic, or aphakic eyes. PMID- 11195753 TI - Subretinal hemorrhage from a retinal arterial macroaneurysm simulating a choroidal melanoma. PMID- 11195754 TI - Anxiety sensitivity in social phobia: comparison between social phobics with and without panic attacks. AB - The current study examines levels of anxiety sensitivity among social phobic patients with and without panic attacks. Two-hundred fourteen individuals with a primary diagnosis of social phobia completed the Anxiety Sensitivity Index (ASI) prior to treatment. Social phobics who experienced panic attacks reported higher levels of anxiety sensitivity than those without panic attacks. Patterning of response to ASI items differed between panicking and non-panicking patients, with the panicking patients reporting greater fear of catastrophic consequences of bodily sensations. Individuals with an additional diagnosis of panic disorder did not differ from those with exclusively situational panic attacks. The findings suggest the importance of examining differences between anxiety-disordered individuals who experience panic attacks and their non-panicking counterparts. PMID- 11195755 TI - Generalization of social anxiety to sporting and athletic situations: gender, sports involvement, and parental pressure. AB - Although researchers have documented that social anxiety may occur in a wide range of interpersonal and performance situations, little attention has been paid to the potential influence of social anxiety on participation in athletics or physical activity. The performance demands of sport and potential social evaluative nature of exercise make it likely that social anxiety would generalize to these situations. Given the physical and psychological benefits of engaging in regular physical activity, avoidance of such activities by socially anxious individuals may have profound health consequences. One-hundred and eighty undergraduate university students completed a battery of standardized social anxiety measures, and a series of 5-point Likert-type questions examining fear and avoidance of sporting and athletic situations. Results indicated that social anxiety and fear of negative evaluation were generally related to social evaluative fears in sporting or athletic situations, particularly for women. Furthermore, social anxiety was positively correlated with avoidance of individual sporting activities, but not with avoidance of team activities. Further analyses revealed social anxiety did not differ by competition level. However, for men, familial pressure to play sports during high school was associated with higher fear of negative evaluation. Implications for the assessment and treatment of social anxiety disorder are discussed. PMID- 11195756 TI - Attention to bodily sensations: a test of the cognitive-attentional model of panic. AB - This paper describes a study designed to test the cognitive-attentional model of panic. This model suggests that attention to internal sensations is likely to increase misinterpretation of them as representing a serious threat to health, which in turn might increase anxiety. In the present study, instructions for internal attentional focus were predicted to increase symptom reporting, anxiety, and catastrophic symptom attributions. Two groups, patients diagnosed with panic disorder with agoraphobia (PDA) and normal controls, watched a stressful film; half of each group was asked to attend to their internal sensations while watching, and the other half to focus on the film. In the normal controls, the manipulation was effective in modifying attentional focus, and the self-focused attention group became more anxious, reported more symptoms, and made more negative symptom attributions. However, in the PDA group, attentional focus was high in both conditions, and perhaps for this reason the intervention had no effect on mood, symptoms, catastrophic cognitions, or symptom attribution. PMID- 11195757 TI - Perception of emotions in anxious and learning disabled children. AB - This study examined differences in the ability to perceive others' emotions in anxious and learning disabled children, as these differences may contribute to these children's unique socio-emotional difficulties and therapeutic needs. Forty six children ages 8 to 12 with either anxiety disorders (ANX), language-based learning disabilities (LD), both conditions, or neither condition (clinical controls) were compared on the DANVA, a standardized measure of auditory and visual perception of emotion. Group results were then compared to normative data. Using multivariate analyses, significant group differences were found on the auditory portion of the DANVA but not on the visual portion. LD and comorbid children scored lower on several auditory stimuli, especially when presented at low emotional intensity, while ANX and comorbid children showed high accuracy for auditory sadness. Comorbid children also had lower auditory DANVA scores than the normative sample. No interactive effects between ANX and LD were found. ANX and LD each appear to have distinct effects on the auditory perception of others' emotions. Children with both conditions show both effects and differ from normal children in this domain. Replication using larger samples is required. PMID- 11195758 TI - Generalized anxiety disorder in older adults: examining the relation between clinician severity ratings and patient self-report measures. AB - Generalized anxiety disorder (GAD) is the most prevalent of the chronic anxiety disorders for older adults. Although a variety of self-report measures are beginning to be utilized to assess anxiety and related symptoms in older adults, there is a paucity of data regarding the convergence of self-report measures with clinician ratings of symptom severity. This situation is problematic in that interpretability of assessment data is limited, as is our broader understanding of the construct of GAD in an older adult population. To address these issues, we examined convergence across assessment modalities among 64 older adults who met diagnostic criteria for GAD. In addition to two Anxiety Disorders Interview Schedule for DSM-IV (ADIS-IV) interviews conducted by independent raters, participants completed four self-report measures (Penn State Worry Questionnaire [PSWQ], Worry Scale [WS], State-Trait Anxiety Inventory [STAI], Beck Depression Inventory [BDI]) as part of a more extensive pretreatment assessment battery. Results revealed significant correlations between clinician-rated GAD severity and the BDI, STAI, and PSWQ. Regression analyses indicated that the BDI (r2 = .15) and the PSWQ (r2 = .07) were particularly useful predictors of clinician rated GAD severity. A comorbid mood disorder, however, was identified as an important mediator of these relations. Specifically, presence of coexistent depression accounted for 17% of the variance in clinician severity ratings (CSR; P < .01), with individuals diagnosed with a comorbid mood disorder receiving higher clinician severity ratings. The only self-report measure that accounted for additional significant variance was the PSWQ (7%). The study highlights the need to address coexistent psychological conditions when examining convergence between assessment modalities, and expands upon the relatively neglected area of anxiety assessment in older individuals. Specifically, the BDI and the PSWQ are identified as particularly useful screening instruments that may be helpful in conceptualizing GAD severity within an older adult population. PMID- 11195759 TI - Age effects on the social interaction test in early adulthood male rats. AB - The effects of age on active and passive social interaction were studied in Wistar rats using the social interaction test (S.I.T.). Individual behaviors such as ambulation, rearing, and defecation were also studied. Despite the widespread use of the S.I.T. in anxiety research, the effects of age on the S.I.T. have not been studied thoroughly. Male Wistar rats of 75, 135, and 180 days old were used. Our results showed age effects on active social contact, passive social contact, ambulation, rearing, and defecation. At 135 days old, animals presented the lowest scores on active social behavior and the highest scores on defecation. Moreover, exploratory behavior measured by ambulation and rearing decreased with age. These results suggest that age could be a relevant variable in the social interaction test. PMID- 11195760 TI - Comorbidity in chronic shyness. PMID- 11195761 TI - Acute onset and remission of obsessions and compulsions following medical illnesses and stress. AB - Obsessive Compulsive Disorder (OCD) is generally chronic. Episodic OCD with complete remission has been rarely reported. Two cases of brief, episodic obsessions and compulsions that appeared for the first time following psychological stress and in the context of medical illness are reported. The possibility of brief episodes of OCD precipitated by stress is illustrated. Exploration of this phenomenon may help us learn more about OCD in general. PMID- 11195762 TI - Obstetric care in patients with HIV disease. AB - Appropriate management of pregnant patients who have human immunodeficiency virus (HIV) disease can have a major impact on maternal and infant health. The goals of therapy are to properly manage the pregnancy, treat the maternal HIV infection and minimize the risk of vertical transmission of HIV. Early detection of HIV through aggressive screening programs is necessary to initiate timely therapy. Zidovudine therapy given antepartum and intrapartum to the mother and after birth to the newborn has been shown to decrease the risk of vertical transmission. Evidence suggests that more aggressive antiretroviral therapy for the mother, which allows suppression of viral loads to undetectable levels, may be safe and may provide significant additional benefits. However, treatment needs to be individualized, weighing the possible teratogenic risks against the benefits of decreased transmission. Multiple prospective cohort studies support elective cesarean section as an additional means to decrease vertical transmission, but its role in relation to other therapies has not been determined. As in nonpregnant patients infected with HIV, prevention of opportunistic infections and adequate psychosocial support are essential. PMID- 11195763 TI - Photo quiz. Nodules in a linear distribution. PMID- 11195764 TI - The 2001 recommended childhood immunization schedule. PMID- 11195765 TI - A patient seeking disability. PMID- 11195766 TI - Office laboratory medicine. American Academy of Family Physicians. PMID- 11195767 TI - Spiritual assessment in medical practice. PMID- 11195768 TI - Spirituality and medical practice: a look at the evidence. PMID- 11195769 TI - Providing basic spiritual care for patients: should it be the exclusive domain of pastoral professionals? PMID- 11195770 TI - New insights into mental illness. PMID- 11195771 TI - Family physicians and end-of-life care. PMID- 11195772 TI - Adult rhinosinusitis: diagnosis and management. AB - Rhinosinusitis can be divided among four subtypes: acute, recurrent acute, subacute and chronic, based on patient history and a limited physical examination. In most instances, therapy is initiated based on this classification. Antibiotic therapy, supplemented by hydration and decongestants, is indicated for seven to 14 days in patients with acute, recurrent acute or subacute bacterial rhinosinusitis. For patients with chronic disease, the same treatment regimen is indicated for an additional four weeks or more, and a nasal steroid may also be prescribed if inhalant allergies are known or suspected. Nasal endoscopy and computed tomography of the sinuses are reserved for circumstances that include a failure to respond to therapy as expected, spread of infection outside the sinuses, a question of diagnosis and when surgery is being considered. Laboratory tests are infrequently necessary and are reserved for patients with suspected allergies, cystic fibrosis, immune deficiencies, mucociliary disorders and similar disease states. Findings on endoscopically guided microswab culture obtained from the middle meatus correlate 80 to 85 percent of the time with results from the more painful antral puncture technique and is performed in patients who fail to respond to the initial antibiotic selection. Surgery is indicated for extranasal spread of infection, evidence of mucocele or pyocele, fungal sinusitis or obstructive nasal polyposis, and is often performed in patients with recurrent or persistent infection not resolved by drug therapy. PMID- 11195773 TI - Spirituality and medical practice: using the HOPE questions as a practical tool for spiritual assessment. AB - The relationship between spirituality and medicine has been the focus of considerable interest in recent years. Studies suggest that many patients believe spirituality plays an important role in their lives, that there is a positive correlation between a patient's spirituality or religious commitment and health outcomes, and that patients would like physicians to consider these factors in their medical care. A spiritual assessment as part of a medical encounter is a practical first step in incorporating consideration of a patient's spirituality into medical practice. The HOPE questions provide a formal tool that may be used in this process. The HOPE concepts for discussion are as follows: H--sources of hope, strength, comfort, meaning, peace, love and connection; O--the role of organized religion for the patient; P--personal spirituality and practices; E- effects on medical care and end-of-life decisions. PMID- 11195774 TI - Management of ankle sprains. AB - Without adequate care, acute ankle trauma can result in chronic joint instability. Use of a standardized protocol enhances the management of ankle sprains. In patients with grades I or II sprains, emphasis should be placed on accurate diagnosis, early use of RICE (rest, ice, compression and elevation), maintenance of range of motion and use of an ankle support. Sprains with complete ligament [corrected] tears (grade III) may require surgical intervention. Although early motion and mobility are recommended, ligamentous strength does not return until months after an ankle sprain. PMID- 11195775 TI - Complementary medicine: viable models. AB - Complementary medicine has had a quiet, consumer-based, grassroots evolution, generally spearheaded by individual champions. In this article, McGrady describes six models of complementary medicine and details specific practitioners who have implemented these models. Solo practitioners, physician-based practices, academic and research initiatives, wellness centers, provider networks, and hospital-based initiatives are discussed to display the diversity of options for complementary medicine. In addition, the author touches upon the legalities and credentialing of practitioners, as well as the financial considerations that health systems must face. PMID- 11195776 TI - Complementary and alternative medicine: an opportunity for reform. AB - Healthcare in the United States is in the midst of a grassroots consumer movement as the use of complementary and alternative medicine (CAM) continues to increase. Traditional health providers find themselves in the unenviable and challenging position of being late entrants into a market that in theory could provide some ready cash at a time when reimbursement is scarce. This article first takes a look at the numbers involved in CAM, and from that foundation predicts future trends involving CAM, discusses the challenge presented to providers and insurers, and offers up the opportunities for systems providing CAM to consumers. While the task of incorporating CAM into the traditional healthcare system may seem daunting, systems that bring CAM into their continuum of care can take heart that millions of people and billions of dollars are just waiting for a new approach that adds value to health and quality to life. PMID- 11195777 TI - Observations from a bottom-line-oriented true believer. AB - While it is difficult to find two people who agree on the definition of complementary medicine, the McGrady and Freshley and Carlson articles help substantially in creating a common definition. This information should help to move providers and practitioners to a better understanding of complementary medicine and its inevitable presence on the American healthcare scene. In the post-Balanced Budget Act era, healthcare executives and physicians recognize that a business-as-usual approach to the delivery of healthcare services is not an option. Cultivating new sources of revenue and having a retail rather than a reimbursement mindset of new ventures is essential. The $13.7 billion dollars being spent annually on complementary medicine is money hospitals can no longer afford to leave on the table. If complementary medicine is approached with the proper philosophical and leadership commitment, and is truly accepted as an important component in the continuum of care, financial success will follow. PMID- 11195778 TI - We are a nation of lonely molecules. PMID- 11195779 TI - Alternatives that work--an insurer's path to integrated healthcare. PMID- 11195780 TI - Characterization of the 5'-flanking region of the rat TIS11 gene. AB - To understand the mechanism underlying the transcriptional regulation of the immediate early gene TIS11, we characterized the 5'-flanking region of the rat TIS11 gene. When fused to the luciferase reporter gene, the 5.3-kb 5'-flanking region of the rat TIS11 gene exhibited functional promoter activity in pheochromocytoma PC12 and hepatoma H4IIE cells. 5'-Deletion analyses indicated that multiple negative and positive regulatory regions were present in the 5' flanking region, and that some of these regions functioned in a cell type specific manner. Promoter activity of the rat TIS 11 gene was enhanced by phorbol 12-myristate 13-acetate (PMA) in both cell lines, and the PMA-responsiveness resided within the 5'-flanking region. The induction of promoter activity by PMA was completely blocked by GF109203X or PD98059, inhibitors of protein kinase C and mitogen-activated protein (MAP) kinase kinase, respectively. These results suggested that induction of the rat TIS 11 promoter by PMA is mediated by activation of the protein kinase C/MAP kinase cascade. PMID- 11195781 TI - The type of DNA attachment sites recovered from nuclear matrix depends on isolation procedure used. AB - A large variety of DNA sequences have been described in nuclear matrix attachment regions. It could be most likely a result of the different methods used for their isolation. The idea about how different types of known DNA sequences (strongly attached to the nuclear matrix, weakly attached, or not attached) directly participate in anchoring DNA loops to the nuclear matrices isolated by different experimental procedures was tested in this study. Matrix-attached (M) and matrix independent or loop (L) fractions as well as nuclear matrices were isolated using extractions of nuclei with 25 mM lithium 3,5-diiodosalicylate (LIS), 2 M NaCl, 0.65 M ammonium sulphate containing buffers followed by DNase I/RNase A digestion, or according to so designated conventional method. Using PCR-based and in vitro binding assays it was established that LIS and ammonium sulphate extractions gave similar results for the type of attachment of sequences investigated. The harsh extraction with 2 M NaCl or the conventional procedure led to some rearrangements in the attachment of DNA loops. As a result a big part of matrix attached sequences were found detached in the loop fractions. However, the in vitro binding abilities of the MARs to the nuclear matrices isolated by different methods did not change. PMID- 11195782 TI - Alpha-1 adrenergic signaling in a cardiac murine atrial myocyte (HL-1) cell line. AB - Activation of alpha-1 adrenergic receptors in the heart has been shown to result in increased contractile activity, cardiac fetal gene re-expression, and myocyte hypertrophy. Three alpha-1 adrenergic receptors have been identified through molecular cloning. Due to the limited selectivities of the currently available alpha-1 adrenergic receptor antagonists, the signaling pathways activated by specific subtypes in the heart remain unresolved. To resolve this dilemma, we have used a molecular approach to identify the signaling pathways and downstream genes that are engaged in response to activation of individual alpha-1 adrenergic subtypes in cardiac cells. We have transfected constitutively active alpha-1 adrenergic receptors (alpha1a-S290/293-AR [1] or the alpha1b-S288/294-AR [2]) subtypes into the cardiac murine myocyte cell line (HL-1) and studied the signal transduction pathway(s) and cardiac gene(s) activated by them. In this study, we demonstrate that the alpha1a-S290/293 -AR [1] subtype preferentially couples to cardiac-specific atrial natriuretic factor (ANF) gene expression, while the alpha1b-S288/294-AR preferentially couples to activation of mitogen-activated protein kinase (MAPK), Ets-like transcription factor-1 (Elk1) and serum response element (SRE) signaling pathways. Endogenous alpha-1 adrenergic receptors are expressed, and stimulate phosphatidylinositol-hydrolysis upon activation with the alpha-1 agonist, phenylephrine. PMID- 11195783 TI - Protein nitration. AB - Various proteins/enzymes obtained commercially were tested for the presence of endogenously nitrated tyrosine by Western blot analysis omitting reducing agent in the step of SDS-PAGE. Histones II-S and VIII-S, IgG, cAMP-dependent protein kinase (PKA), phosphorylase b, and phosphorylase kinase exhibited strong immunoreactive bands. Histone VI-S, glycogen synthase, lactate dehydrogenase, actin, thyroglobulin, and macroglobulin exhibited moderate immunoreactivity. Histone III-S, casein, acetyl cholinesterase, DNase I, and lipase had only traceable immunoreactivity. Whereas histone VII-S, pyruvate kinase, trypsin, pepsin, chymotrypsin, protease IV, and protease XIII, and glutathione S transferase lacked immunoreactivity. A variation of immunoreactivity between hypertensive and normaltensive rat hearts was found in the histone-agarose fractions of crude extracts. Additionally, nitrotyrosine immunoreactivity was observed in non-mammalian organisms including Eschericia coli, Saccharomyces cerevisiae and Triticum vulgaris. Upon the treatment of 15 microM peroxynitrite (PN), strong oxidant derived from nitric oxide (NO), the apparent Km of PKA for cAMP increased from approximately 10(-8) to 10(-6) M. The results imply that the varied nitration of tyrosine residues in proteins/enzymes may occur as a post translational modification in vivo, and such discriminative nitration may be vital in PN/NO-regulated signal transduction cascade. PMID- 11195786 TI - Vascular endothelial growth factor is increased following coronary artery occlusion in the dog heart. AB - Vascular endothelial growth factor (VEGF) is a hypoxia-inducible factor expressed into several molecular forms in mammalian tissues of which VEGF 120, VEGF 164, and VEGF 188 are the major isoforms. While VEGF 164 is the predominant isoform in most tissues, VEGF 188 has been reported to be dominant in cardiac tissues such as that in guinea pig, rat, and mouse. In the dog heart, an important model for studies of myocardial ischemia and angiogenesis, the expression of VEGF remains to be established. We investigated the expression of the various isoforms of VEGF in normal and ischemic dog heart tissues using Reverse transcription-Polymerase chain reaction, Ribonuclease Protection Assay and Western blotting. The nucleotide sequences of the major isoforms of VEGF were also determined using homology cloning techniques. Our study showed that the nucleotide sequences of dog VEGF were highly homologous to human VEGF especially in the c-terminal region spanning exons 58. A single amino acid-deletion (Glu5 in human VEGF), similar to that reported in other animal species, was observed in the major isoforms resulting in monomers of 120, 164, and 188 amino acids. A novel splice site similar to that in human VEGF183 was also identified in the dog heart, resulting in the 182 amino acid-containing isoform (VEGF 182). Moreover, VEGF 164 was expressed at a higher level as compared with VEGF 182 or VEGF 188 in both normal and ischemic tissues. The identification of the nucleotide sequences of VEGF isoforms in the dog heart should prove useful in investigating the molecular expression of VEGF in canine tissues. PMID- 11195785 TI - Lysosome lipid storage disorder in NCTR-BALB/c mice: spleen and lung lysosomes store unesterified cholesterol but differ in their phospholipid composition. AB - A strain derived from a colony of BALB/c mice at the National Center for Toxicological Research, Jefferson, AR, USA (NCTR-BALB/c) suffers from an autosomal recessive disorder characterized by proliferation of secondary lysosomes with accumulation ofunesterified cholesterol in several tissues. The unesterified cholesterol content of spleens and lungs from the affected mice were elevated 8- and 3-fold respectively over age- and sex-matched controls. Postnuclear supernatants of tissue homogenates were fractionated by sucrose density gradient centrifugation and the fractions were analyzed for unesterified cholesterol, protein and marker enzyme activities for lysosomes (N-acetyl-beta-D glucosaminidase, beta-D-glucuronidase), plasma membrane (alkaline phosphodiesterase I), endoplasmic reticulum (glucose-6-phosphatase) and mitochondria (cytochrome oxidase). The enzyme distribution profile showed that lysosomes of affected tissues floated at low density regions (density 1.05-1.08) of the gradient and contained substantial amount of tissue unesterified cholesterol. These low density lysosomes were purified about 17-fold (58% yield) from spleen and about 6-fold (32% yield) from lungs with minimal contamination by other organelles They were mostly intact as judged by high latency for N-acetyl beta-D-glucosaminidase activity (70-100%). Lysosomes of control tissues were not found at the low density regions. The distribution profiles for other organelles were similar between affected and control tissues. Phospholipid composition of low density lysosomes were distinctly different from their respective tissue homogenates. Spleen and lung lysosomes were enriched in sphingomyelin and phosphatidylcholine respectively. The results suggest that these lysosomes acquire their low densities due to accumulation of unesterified cholesterol, the retention of which may be aided by sphingomyelin and phosphatidylcholine content of the lysosomes. PMID- 11195787 TI - Effect of ethylisopropyl amiloride, a Na+ - H+ exchange inhibitor, on cardioprotective effect of ischaemic and angiotensin preconditioning. AB - The present study is designed to investigate the role of Na+ -H+ exchanger in the cardioprotective effect of ischaemic and angiotensin (Ang II) preconditioning. Isolated perfused rat heart was subjected to global ischaemia for 30 min followed by reperfusion for 120 min. Coronary effluent was analysed for LDH and CK release to assess the degree of cardiac injury. Myocardial infarct size was estimated macroscopically using TTC staining. Left ventricular developed pressure (LVDP) and dp/dt were recorded to evaluate myocardial contractility. Four episodes of ischaemic or Ang II preconditioning markedly reduced LDH and CK release in coronary effluent and decreased myocardial infarct size. 5-(N-ethyl-N isopropyl)amiloride (EIPA), a Na+ - H+ exchange inhibitor, produced no marked effect on ischaemic preconditioning and Ang II preconditioning induced cardioprotection. On the other hand, EIPA administration prior to global ischaemia produced a similar reduction in myocardial injury as was noted with ischaemic preconditioning or Ang II preconditioning. On the basis of these results, it may be concluded that inhibition of Na+ - H+ exchanger protects against ischaemia-reperfusion induced myocardial injury whereas activation of Na+ - H+ exchanger may not mediate the cardioprotective effect of ischaemic and Ang II preconditioning. PMID- 11195784 TI - Modification of beta-adrenoceptor signal transduction pathway by genetic manipulation and heart failure. AB - The beta-adrenoceptor (beta-AR) mediated signal transduction pathway in cardiomyocytes is known to involve beta1- and beta2-ARs, stimulatory (Gs) and inhibitory (Gi) guanine nucleotide binding proteins, adenylyl cyclase (AC) and cAMP-dependent protein kinase (PKA). The activation of beta1- and beta2-ARs has been shown to increase heart function by increasing Ca2+ -movements across the sarcolemmal membrane and sarcoplasmic reticulum through the stimulation of Gs proteins, activation of AC and PKA enzymes and phosphorylation of the target sites. The activation of PKA has also been reported to increase phosphorylation of some myofibrillar proteins (for promoting cardiac relaxation) and nuclear proteins (for cardiac hypertrophy). The activation of beta2-AR has also been shown to affect Gi-proteins, stimulate mitogen activated protein kinase and increase protein synthesis by enhancing gene expression. Beta1- and beta2-ARs as well as AC are considered to be regulated by PKA- and protein kinase C (PKC) mediated phosphorylations directly; both PKA and PKC also regulate beta-AR indirectly through the involvement of beta-AR kinase (betaARK), beta-arrestins and Gbeta gamma-protein subunits. Genetic manipulation of different components and regulators of beta-AR signal transduction pathway by employing transgenic and knockout mouse models has provided insight into their functional and regulatory characteristics in cardiomyocytes. The genetic studies have also helped in understanding the pathophysiological role of PARK in heart dysfunction and therapeutic role of betaARK inhibitors in the treatment of heart failure. Varying degrees of defects in the beta-AR signal transduction system have been identified in different types of heart failure to explain the attenuated response of the failing heart to sympathetic stimulation or catecholamine infusion. A decrease in beta1-AR density, an increase in the level of G1-proteins and overexpression of betaARK are usually associated with heart failure; however, these attenuations have been shown to be dependent upon the type and stage of heart failure as well as region of the heart. Both local and circulating renin-angiotensin systems, sympathetic nervous system and endothelial cell function appears to regulate the status of beta-AR signal transduction pathway in the failing heart. Thus different components and regulators of the beta-AR signal transduction pathway appears to represent important targets for the development of therapeutic interventions for the treatment of heart failure. PMID- 11195788 TI - Protein kinase C is involved in cardioprotective effects of ischemic preconditioning on infarct size and ventricular arrhythmia in rats in vivo. AB - Protein kinase C (PKC) has been known to play an important role in ischemic preconditioning (IP). This study was designed to examine whether the translocation of PKC is associated with the cardioprotective effects of IP in vivo on infarct size and ventricular arrhythmias in a rat model. Using anesthetized rats, heart rate, systolic blood pressure, infarct size and ventricular arrhythmias during 45 min of coronary occlusion were measured. PKC activity was assayed in both the cytosolic and cell membrane fraction. Brief 3 min periods ofischemia followed by 10 min ofreperfusion were used to precondition the myocardium. Calphostin C was used to inhibit PKC. Infarct size was significantly reduced by IP (68.1 (2.5)%, mean (S.E.) vs. 45.2 (3.4)%, p < 0.01). The reduction in infarct size by IP was abolished by pretreatment with calphostin C. The total number of ventricular premature complex (VPC) during 45 min of coronary occlusion was reduced by IP (1474 (169) beats/45 min vs. 256 (82) beats/45 min, p < 0.05). The reduction the total number of VPC induced by IP was abolished by the administration of calphostin C before the episode of brief ischemia. The same tendency was observed in the duration of ventricular tachycardia and the incidence of ventricular fibrillation. PKC activity in the cell membrane fraction transiently increased immediately after IP (100 vs. 142%, p < 0.01) and returned to baseline 15 min after IP. Pretreatment with calphostin C prevented the translocation of PKC. The translocation of PKC plays an important role in the cardioprotective effect of IP on infarct size and ventricular arrhythmias in anesthetized rats. PMID- 11195789 TI - Calpain-mediated proteolytic cleavage of troponin I induced by hypoxia or metabolic inhibition in cultured neonatal cardiomyocytes. AB - While ischemic damage to myofibrillar proteins is thought to be responsible in part for depressed cardiac function, the relation between myofilament protein breakdown and chronic hypoxia has not been defined. We previously characterized a chemical hypoxia model of neonatal cardiomyocytes mediated by 1 mM azide that exhibits features of calpain activation (Mol Cell Biochem 178:141-149, 1998). We here show that both hypoxia and azide-mediated metabolic inhibition induced heme oxygenase-1 expression, and caused cell death associated with lipid peroxidation. While blocking calcium influx or inhibiting calpain activity efficiently attenuated hypoxia-induced cell injury, it failed to prevent cell injury caused by adenoviral overexpression of the tumor suppressor protein p53. Inhibitors of caspases, on the other hand, suppressed cell injury caused by p53 overexpression. Hypoxia caused selective cleavage of troponin I (TnI), which could be suppressed by either nifedipine or calpeptin. Other myofilament proteins such as troponin T, myosin heavy chain, and actin appeared to remain largely intact. p53-mediated cell injury exhibited proteolysis of the caspase protein substrate lamin B without appreciable breakdown of TnI. We suggest that calpain-induced TnI breakdown may constitute a unique biochemical marker associated with chronically hypoxic cardiomyocytes. PMID- 11195790 TI - Effect of sex and bezafibrate on incorporation of blood borne palmitate into lipids of rat liver nuclei. AB - The aim of the present study was to investigate whether lipid metabolism in the nuclei is affected by changes in the metabolism of free fatty acids in the liver. The experiments were carried out on 3 groups of rats: 1 - control-male, 2 - female, and 3 - male, treated with bezafibrate (a peroxisome proliferator). The rats received 14C-palmitic acid intravenously. Thirty min later liver samples and blood from the abdominal aorta were taken. The liver nuclei were isolated in sucrose gradient. Lipids were extracted from the nuclei and the liver homogenate and subsequently separated into the following fractions: phospholipids, mono, di- and triacylglycerols, free fatty acids, cholesterol and cholesterol esters. The radioactivity of each fraction was counted. Furthermore, the content of free fatty acids and the fatty acid binding proteins was measured. It was found that radioactivity was present in each lipid fraction obtained from the liver homogenate and from the nuclei. In the female group, the total radioactivity of lipids in the liver homogenate was lower, whereas in the nuclei it was higher in comparison to the male group. The reduction in the radioactivity in the liver was mostly accounted for by decreased radioactivity in the fraction oftriacylglycerols and phospholipids. In the nuclei, the radioactivity of the fraction of phospholipids, free fatty acids and diacylglycerols was elevated. Bezafibrate did not affect the total radioactivity of lipids in the liver and reduced it in the nuclei. In the liver, the drug increased radioactivity mostly in the fraction of phospholipids and reduced it mainly in the fraction of triacylglycerols. In the nuclei, the radioactivity of each lipid fraction examined was reduced. The content of the fraction of free fatty acids in the liver and in the nuclei in the female and in the bezafibrate-treated groups did not differ from the respective value in the control group. The content of fatty acid binding proteins in the nuclei of the female and bezafibrate-treated groups increased in parallel to the elevation in their content in the cytosol. It is concluded that the female sex hormones and bezafibrate influence the transport of selected lipids into the nuclei. The effects seem to be a consequence of the action of these factors directly on the nucleus. PMID- 11195791 TI - Evidence that the TRP-1 protein is unlikely to account for store-operated Ca2+ inflow in Xenopus laevis oocytes. AB - The role of the TRP-1 protein, an animal cell homologue of the Drosophila transient receptor potential Ca2+ channel, in store-operated Ca2+ inflow in Xenopus laevis oocytes was investigated. A strategy involving RT-PCR and 3' and 5' rapid amplification of cDNA ends (RACE) was used to confirm and extend previous knowledge of the nucleotide and predicted amino acid sequences of Xenopus TRP-1 (xTRP-1). The predicted amino acid sequence was used to prepare an anti-TRP-l polyclonal antibody which detected the endogenous oocyte xTRP-1 protein and the human TRPC-1 protein expressed in Xenopus oocytes. Ca2+ inflow (measured using fura-2) initiated by 3-deoxy-3-fluoroinositol 1,4,5-trisphosphate (InsP3F) or lysophosphatidic acid (LPA) was completely inhibited by low concentrations of lanthanides (IC50 = 0.5 microM), indicating that InsP3F and LPA principally activate store-operated Ca2+ channels (SOCs). Antisense cRNA or antisense oligodeoxynucleotides, based on different regions of the xTRP-1 cDNA sequence, when injected into Xenopus oocytes, did not inhibit InsP3F-, LPA- or thapsigargin-stimulated Ca2+ inflow. Oocytes expressing the hTRPC-1 protein, which is 96% similar to xTRP-1, exhibited no detectable enhancement of either basal or InsP3F-stimulated Ca2+ inflow and only a very small enhancement of LPA stimulated Ca2+ in-flow compared with control oocytes. It is concluded that the endogenous xTRP-1 protein is unlikely to be responsible for Ca2+ inflow through the previously-characterised Ca2+ -specific SOCs which are found in Xenopus oocytes. It is considered that xTRP-1 is likely to be a receptor-activated non selective cation channel such as the channel activated by maitotoxin. PMID- 11195792 TI - Three dimensional atomic model and experimental validation for the ATP-Regulated Module (ARM) of the atrial natriuretic factor receptor guanylate cyclase. AB - Atrial natriuretic factor (ANF) receptor guanylate cyclase (ANF-RGC) is a single chain transmembrane-spanning protein, containing both ANF binding and catalytic activities. ANF binding to the extracellular receptor domain activates the cytosolic catalytic domain, generating the second messenger cyclic GMP. Obligatory in this activation process is an intervening transduction step, which is regulated by the binding of ATP to the cyclase. The partial structural motif of the ATP binding domain of the cyclase has been elucidated and has been termed ATP Regulatory Module (ARM). The crystal structures of the tyrosine kinase domains of the human insulin receptor and haematopoietic cell kinase were used to derive a homology-based model of the ARM domain of ANF-RGC. The model identifies the precise configuration of the ATP-binding pocket in the ARM domain, accurately represents its ATP-dependent features, and shows that the ATP-dependent transduction phenomenon is a two-step mechanism. In the first step, ATP binds to its pocket and changes its configuration; in the second step, via an unknown protein kinase, it phosphorylates the cyclase for its full activation. PMID- 11195793 TI - Influence of extracellular potassium on the antiarrhythmic effect of global preconditioning in isolated perfused rat hearts. AB - The objective of this study was to investigate if a variation in extracellular-K+ concentrations alters the effects of global pre-conditioning on ischemia-induced arrhythmias. Rat hearts were Langendorff-perfused with Krebs-Henseleit solution and randomised in 8 groups (n = 12/group): four control groups (K+: 2, 4, 6, or 8 mmol/L) which underwent 30-min coronary artery occlusion and four preconditioned groups (K+: 2, 4, 6, or 8 mmol/L) in which the 30-min regional ischemia was preceded by 2 cycles of 3 min global ischemia. In the presence of low K+ (2 mmol/L), there were no differences between control and preconditioning groups in the number of ventricular premature beats (VPBs): 194 +/- 64 vs. 217 +/- 81, the incidence of ventricular tachycardia (VT): 100% vs. 100% and of ventricular fibrillation (VF): 100% vs. 100%. In the presence of normal K+ concentration (4 mmol/L), ischemic preconditioning reduced the number of VPBs from 88 +/- 26 to 25 +/- 10, (p < 0.05), the incidence of VT from 100 to 50% (p < 0.05), and of VF from 67 to 16% (p < 0.05). In the condition of higher K+ concentration (6 mmol/ L), VPBs (34 +/- 8 vs. 11 +/- 4), the incidence of VT (100% vs. 25%; p < 0.05 ) and VF (25% vs. 8%) were further reduced in preconditioned hearts. In the condition of K+ concentration (8 mmol/L), there were no differences in VPBs (11 +/- 3 vs. 7 +/- 2), the incidence of VT (8% vs. 0%) and VF (8% vs. 0%) between control and preconditioned hearts. Our data show that ischemic preconditioning affords protection against arrhythmias during coronary artery occlusion in the isolated rat heart and that hypokalemia abolishes the antiarrhythmic effects of global preconditioning. PMID- 11195794 TI - Alteration of the levels of the M-type 6-phosphofructo-1-kinase mRNA isoforms during neonatal maturation of heart, brain and muscle. AB - During muscle, heart, and brain neonatal maturation, the capacity to utilize glucose in energy metabolism is directly related to the extent of accumulation of the 6-phosphofructo-1-kinase (PFK) M-type subunit. Neonatal development of other organs, such as liver and kidney, which are not characterized by large increases in the capacity to use glucose do not exhibit large increases in the M-type subunit protein. The presence of the M-type subunit in a PFK isozyme pool fosters a higher affinity utilization of carbohydrate and increased responsiveness to the levels of regulatory metabolites. To better appreciate this phenomenon, which is vital for normal development, the different isoforms of the M-type subunit mRNA's and alteration of their levels during maturation have been examined. Further, the potential promoter regions, i.e., the regions upstream from the sites of initiation of transcription, which are involved in expression of the different M type subunit mRNA isoforms have been isolated, sequenced, and examined for possible transcription factor interaction sites. Using cDNA libraries produced from adult rat brain or skeletal muscle RNA, two primary forms of rat M-type subunit cDNA's were detected. Although the translated regions of these mRNA's were essentially identical, the 5'-untranslated region (5'-UTR) exhibited different lengths (90 or 59 bp) and sequences. Each M-type subunit cDNA had 10 common nucleotides immediately upstream from the initiator ATG, and the remaining 5'-UTR's had insignificant identity. A genomic fragment which interacted with probes complimentary to the sequences of the 5'-UTR of each M-type subunit mRNA isoform was isolated and sequenced by primer walking. It was discovered that the 5'-UTR of one of the mRNA's (proximal mRNA) was located immediately upstream from exon I and was apparently transcribed without splicing. Subsequently, the initial bp in the sequence of the other mRNA isoform (distal mRNA) was located 4010 bp upstream from the ATG in exon 1. Employing Reverse Transcription-Polymerase Chain Reaction using total RNA and scanning densitometry, the relative levels of the proximal and distal mRNA's during neonatal maturation of brain, heart, and muscle were measured. In these tissues, both forms of M-type subunit mRNA's were present, and during maturation tissue-specific differences were noted. PMID- 11195795 TI - Methionine 156 in the immunodominant domain of CD36 contributes to define the epitope recognized by the NL07 MoAb. AB - CD36 is a membrane glycoprotein expressed by several cell types, and play a role as a receptor for different physiological and pathological ligands. An immunodominant domain of CD36 has been described in the amino acidic region 155 183, where many ligands and monoclonal antibodies (MoAbs) react. MoAbs against CD36 have proved useful in structural as well as functional studies. One of these antibodies, MoAb NL07, recognizes a conformational epitope that is acquired in the late steps of the CD36 maturation. The NL07 epitope appears to be functionally relevant and blocks CD36-mediated binding to red blood cells infected with the malaria parasite Plasmodium falciparum (IRBC). In this work a mutant COS-7 clone expressing NL07-negative CD36 molecules on the cell surface was investigated. In the mutant, the methionine in position 156 of the wild type CD36 sequence was replaced by a valine. It was determined that methionine 156 was essential for NL07 reactivity, mapping the NL07 epitope to the vicinity of the functionally important immunodominant domain (aa 155-183) of CD36. Although methionine 156 is located in this region, the CD36V156 mutated molecule was apparently functional and able to bind IRBC and oxidized LDL. PMID- 11195797 TI - Multiple sclerosis. PMID- 11195796 TI - Stimulatory effect of genistein and daidzein on protein synthesis in osteoblastic MC3T3-E1 cells: activation of aminoacyl-tRNA synthetase. AB - The effect of genistein and daidzein on protein synthesis in osteoblastic MC3T3 E1 cells in vitro was investigated to determine a cellular mechanism by which the isoflavones stimulate bone formation. Cells were cultured for 48 h in alpha minimal essential medium containing either vehicle, genistein (l0(-7) - 10(-5) M) or daidzein (10(-7) - 10(-5) M). The 5,500 g supernatant of cell homogenate was used for assay of protein synthesis with [3H]leucine incorporation in vitro. The culture with genistein or daidzein caused a significant elevation of protein synthesis in the cell homogenate. The effect of genistein ( 10(-5) M) or daidzein ( 10(-5) M) in elevating protein synthesis was significantly prevented, when cells were cultured for 48 h in a medium containing either actinomycin D (10(-7) M) or cycloheximide (10(-6) M) in the absence or presence of isoflavones. Moreover, when genistein (10(-7) 10(-5) M) or daidzein (10(-6) and 10(-5) M) was added to the reaction mixture containing the cell homogenate obtained from osteoblastic cells cultured without isoflavone, protein synthesis was significantly raised. This increase was markedly blocked by the addition of cycloheximide (10(-7) M). In addition, [3H]leucyl-tRNA synthetase activity in the cytosol of osteoblastic cells was significantly increased by the addition of genistein (10(-6) and 10(-5) M) or daidzein (10(-5) M) into the enzyme reaction mixture. The present study demonstrates that genistein or daidzein can stimulate protein synthesis in osteoblastic MC3T3-E1 cells. The isoflavones may have a stimulatory effect on osteoblastic bone formation due to increasing protein synthesis. PMID- 11195798 TI - Multiple sclerosis. PMID- 11195799 TI - Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. PMID- 11195800 TI - Exercise-induced premature ventricular depolarizations. PMID- 11195801 TI - Treatment of ectopic pregnancy. PMID- 11195802 TI - Repair of large bone defects with the use of autologous bone marrow stromal cells. PMID- 11195803 TI - Transmission of glomerular permeability factor from a mother to her child. PMID- 11195804 TI - 4th International Workshop on Pore-Forming Toxins. 14-17 September 2000, Trento, Italy. Abstracts. PMID- 11195805 TI - Bovine welfare spotlighted at annual forum. PMID- 11195806 TI - Drug compounding position statement adopted. PMID- 11195807 TI - Innovator in bovine housing standards gains welfare award. PMID- 11195808 TI - Natural bovine behavior key to evaluating management practices. PMID- 11195809 TI - Raising contented cattle makes welfare, production sense. PMID- 11195810 TI - Livestock shows a lesson in ethics, animal care. PMID- 11195811 TI - Welfare of animals integral part of professional rodeos. PMID- 11195812 TI - Assessing the state of the cattle slaughter industry. PMID- 11195813 TI - Feels acupuncture lacks scientific evidence. PMID- 11195814 TI - Opinions regarding the ECFVG program. PMID- 11195815 TI - Opinions regarding the ECFVG program. PMID- 11195816 TI - Opinions regarding the ECFVG program. PMID- 11195817 TI - AVAR defends accuracy of references. PMID- 11195818 TI - Believes aggression is more common in some dog breeds. PMID- 11195819 TI - Views on insurance and veterinary economics. PMID- 11195820 TI - Views on insurance and veterinary economics. PMID- 11195821 TI - Views on insurance and veterinary economics. PMID- 11195822 TI - Information on parasitic gastrointestinal tract infections in cats. PMID- 11195823 TI - Preparing today's veterinarians for a nontraditional future. PMID- 11195824 TI - Theriogenology question of the month. Endometrial cups. PMID- 11195825 TI - Steroidogenic response of adrenal tissues after administration of ACTH to dogs with hypercortisolemia. AB - OBJECTIVE: To evaluate adrenal sex hormone concentrations in neutered dogs with hypercortisolemia. DESIGN: Case series. ANIMALS: 11 neutered dogs with hypercortisolemia. PROCEDURE: Serum samples obtained before and 1 hour after administration of ACTH were evaluated for concentrations of cortisol, progesterone, testosterone, dehydroepiandrosterone sulfate or androstenedione or both, and 17-hydroxyprogesterone. RESULTS: For all dogs, concentrations of 1 or more adrenal sex hormones were substantially greater than reference range values before or after administration of ACTH. Testosterone concentration was not greater than reference range values in any of the dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results emphasize the importance of ruling out hypercortisolemia before measuring adrenal sex hormone concentrations as a means of diagnosing adrenal hyperplasia syndrome (alopecia X) in dogs. PMID- 11195826 TI - Long-term outcome of gonadectomy performed at an early age or traditional age in dogs. AB - OBJECTIVE: To determine long-term results and complications of gonadectomy performed at an early age (prepubertal) or at the traditional age in dogs. DESIGN: Cohort study. ANIMALS: 269 dogs from animal shelters. PROCEDURE: Dogs that underwent gonadectomy were allotted to 2 groups on the basis of estimated age at surgery (traditional age, > or =24 weeks old; prepubertal, < 24 weeks old). Adoptive owner information was obtained from shelter records, and telephone interviews were conducted with owners to determine physical or behavioral problems observed in the dogs since adoption. Follow-up information was obtained from attending veterinarians for dogs with complex problems or when owners were uncertain regarding the exact nature of their dog's problem. RESULTS: Prepubertal gonadectomy did not result in an increased incidence of behavioral problems or problems associated with any body system, compared with traditional-age gonadectomy, during a median follow-up period of 48 months after gonadectomy. Rate of retention in the original adoptive household was the same for dogs that underwent prepubertal gonadectomy as those that underwent traditional-age gonadectomy. Infectious diseases, however, were more common in dogs that underwent prepubertal gonadectomy. CONCLUSIONS AND CLINICAL IMPLICATIONS: With the exception of infectious diseases, prepubertal gonadectomy may be safely performed in dogs without concern for increased incidence of physical or behavioral problems during at least a 4-year period after gonadectomy. PMID- 11195827 TI - Comparison of in-hospital versus 24-hour ambulatory electrocardiography for detection of ventricular premature complexes in mature Boxers. AB - OBJECTIVE: To evaluate the use of in-hospital electrocardiography (ECG) for detection of ventricular premature complexes (VPC), compared with 24-hour ambulatory ECG. DESIGN: Original study. ANIMALS: 188 Boxers > 9 months old; 31 had a history of syncope, and 157 were healthy (no history of syncope). PROCEDURE: In-hospital ECG was performed on all Boxers for at least 2 minutes. Within 7 days after the in-hospital ECG was completed, 24-hour ambulatory ECG was performed. RESULTS: The specificity of in-hospital ECG was 100% for the detection of at least 50 VPC in a 24-hour period in dogs with syncope and 93% in healthy dogs. In-hospital ECG had poor sensitivity, although sensitivity increased as the number of VPC per 24 hours increased. CONCLUSIONS AND CLINICAL RELEVANCE: Use of in-hospital ECG is highly specific for detection of at least 50 VPC during a 24 hour period. However, in-hospital ECG is insensitive, and a lack of VPC does not suggest that the dog does not have a substantial number of VPC during that same period. The use of in-hospital ECG appears to be inadequate for screening purposes and therapeutic evaluations in mature Boxers with ventricular arrhythmic disease. PMID- 11195828 TI - Suspected caffeine and ephedrine toxicosis resulting from ingestion of an herbal supplement containing guarana and ma huang in dogs: 47 cases (1997-1999). AB - OBJECTIVE: To describe the clinical signs following ingestion of an herbal supplement containing guarana and ma huang in dogs, estimate minimum dose at which clinical signs of toxicosis and death were reported, and evaluate treatment options. DESIGN: Retrospective study. ANIMALS: 47 dogs with evidence of ingestion of an herbal supplement containing primarily guarana and ma huang. PROCEDURE: Records of dogs that had ingested an herbal supplement containing ma huang and guarana between July 1997 and October 1999 were retrieved from the National Animal Poison Control Center database. Data were retrieved and reviewed regarding signalment, dose ingested, clinical signs, laboratory test results, treatment, and final outcome. Cases were assessed by staff veterinarians as toxicosis or suspected toxicosis on the basis of strength of evidence supporting a diagnosis. RESULTS: Most dogs (80%) developed clinical signs of toxicosis within 8 hours of ingestion, and clinical signs persisted for up to 48 hours. Hyperactivity, tremors, seizures, and behavior changes were reported in 83% of dogs; other signs included vomiting (47%), tachycardia (30%), and hyperthermia (28%). Seventeen percent of the dogs died or were euthanatized. Estimated doses of guarana and ma huang ranged from 4.4 to 296.2 mg/kg (1.98 to 133.2 mg/lb) and 1.3 to 88.9 mg/kg (0.58 to 40.0 mg/lb) of body weight, respectively; minimum dose at which death was reported was 19.1 mg of guarana/kg (8.7 mg/lb) and 5.8 mg of ma huang/kg (2.6 mg/lb). CONCLUSIONS AND CLINICAL RELEVANCE: Accidental ingestion of herbal supplements containing primarily guarana and ma huang in dogs can lead to a potentially lethal condition that may require prompt detoxification and supportive treatment for several days. Most dogs recovered with supportive treatment. PMID- 11195829 TI - Radiographic patterns of periodontitis in cats: 147 cases (1998-1999). AB - OBJECTIVE: To determine patterns of alveolar bone loss (periodontitis) and other lesions evident on full-mouth survey radiographs of cats. DESIGN: Retrospective study. ANIMALS: 147 cats. PROCEDURE: Full-mouth radiographs were evaluated for evidence and severity of alveolar bone loss, odontoclastic resorption lesions (ORL), retained roots, missing teeth, signs of endodontic disease secondary to periodontitis, and apical resorption. RESULTS: 106 (72%) cats had some degree of periodontitis, 100 (68%) were missing teeth, 98 (67%) had ORL, 78 (53%) had expansion of the buccal alveolar bone at 1 or more canine teeth, 75 (51%) had retained roots, 48 (33%) had apical resorption, and 12 (8%) had signs of endodontic disease secondary to periodontitis. Cats < 4 years old were not significantly more likely than the general population to have normal alveolar bone height. Prevalence of ORL increased with age, but cats > or =13 years old were less likely than the general population to have moderate or severe generalized periodontitis. Purebred cats were not significantly more likely to have periodontitis or ORL than mixed-breed cats. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that periodontitis is common in cats and that horizontal bone loss is the most common radiographic pattern of alveolar bone loss. Purebred cats were not more likely than mixed-breed cats to have ORL or periodontitis, but when they did have periodontitis, it was more likely to be moderate to severe. Cats with ORL were less likely than cats without ORL to have normal alveolar bone height and more likely to have severe focal vertical bone loss. PMID- 11195830 TI - Intermittent hypoglycemia in a horse with anaplastic carcinoma of the kidney. AB - Clinically apparent hypoglycemia is rare in adult horses. Hypoglycemia is a well recognized paraneoplastic syndrome in humans and dogs with non-insulin-secreting tumors and may occur in horses as well. Hypoglycemia associated with non-insulin secreting tumors is believed to result from production of an abnormal form of insulin-like growth factor II. Neoplasia should be considered in the differential diagnosis for adult horses with hypoglycemia. PMID- 11195831 TI - Outbreaks of clinical mastitis caused by Trichosporon beigelii in dairy herds. AB - Trichosporon beigelii is widely distributed in nature and is classically associated with white piedra, a mycosis that may involve the hair of the human body. Intramammary infections caused by T beigelii may be fatal in cows; the prevalence in affected dairy herds may be high. Affected cows may have hyperthermia, swelling of the udder, and substantially decreased milk production or agalactia. Intramammary infections caused by yeast, including T beigelii, may also be associated with high bacterial counts in bulk-tank milk. PMID- 11195832 TI - Propylene glycol toxicosis in a llama. AB - Propylene glycol toxicosis in llamas can result from overzealous administration of propylene glycol-containing gels formulated and labeled for use in cattle. Treatment of ketosis in llamas requires re-establishment of stomach flora and stimulation of appetite. PMID- 11195833 TI - Use of medetomidine and ketamine for immobilization of free-ranging giraffes. AB - OBJECTIVE: To develop a dosage correlated with shoulder height (SH) in centimeters for effective immobilization of free-ranging giraffes, using a combination of medetomidine (MED) and ketamine (KET) and reversal with atipamezole (ATP). DESIGN: Prospective study. ANIMALS: 23 free-ranging giraffes. PROCEDURE: The drug combination (MED and KET) was administered by use of a projectile dart. Quality of induction, quality of immobilization, and time to recovery following injection of ATP were evaluated. Physiologic variables measured during immobilization included PaO2, PaCO2, oxygen saturation, end-tidal CO2, blood pH, indirect arterial blood pressure, heart and respiratory rates, and rectal temperature. RESULTS: Sixteen giraffes became recumbent with a dosage (mean +/- SD) of 143 +/- 29 microg of MED and 2.7 +/- 0.6 mg of KET/cm of SH. Initially, giraffes were atactic and progressed to lateral recumbency. Three giraffes required casting with ropes for data collection, with dosages of 166 +/- 5 microg of MED and 3.2 +/- 0.6 mg of KET/cm of SH. Four giraffes required administration of etorphine (n = 2) or were cast with ropes (2) for capture but remained dangerous to personnel once recumbent, precluding data collection. In giraffes successfully immobilized, physiologic monitoring revealed hypoxia and increased respiratory rates. Values for PaCO2, end-tidal CO2, and heart rate remained within reference ranges. All giraffes were hypertensive and had a slight increase in rectal temperature. Atipamezole was administered at 340 +/- 20 microg/cm of SH, resulting in rapid and smooth recoveries. CONCLUSIONS AND CLINICAL RELEVANCE: Medetomidine and KET was an effective immobilizing combination for free-ranging giraffes; however, at the dosages used, it does not induce adequate analgesia for major manipulative procedures. Quality of induction and immobilization were enhanced if the giraffe was calm. Reversal was rapid and complete following injection of ATP. PMID- 11195834 TI - Multifocal pyogranulomatous osteomyelitis resembling chronic recurrent multifocal osteomyelitis in a lemur. AB - Chronic recurrent multifocal osteomyelitis is a rare inflammatory bone disease of children and adolescents that is characterized by localized swelling and pain in the clavicles and long bones of the limbs. Diagnosis of chronic recurrent multifocal osteomyelitis is made from clinical signs, characteristic radiographic and histopathologic findings, and negative results of microbial cultures. Treatment of chronic recurrent multifocal osteomyelitis in humans includes administration of nonsteroidal anti-inflammatory drugs or immune modulators, which may be effective in lemurs. PMID- 11195835 TI - [Urinary tract infections in the elderly]. AB - DEFINITIONS: Age over 65 years is generally used to define the elderly population. Urinary tract infections are increasingly frequent after this age. Comorbidity and living conditions in the elderly have a particular incidence on the clinical expression and the bacterial flora involved. Besides these elements, altered cognitive capacity and abnormal urinary function prior to the infection and lead to an atypical clinical presentation. ASYMPTOMATIC BACTERIURIA: Systematic screening has produced a large body of literature on asymptomatic bacteriuria. Our review of the literature leads to the conclusion that systematic bacteriology tests are not warranted in the elderly population in general due to the subsequent risk of germ selection and erroneous diagnosis. PRACTICAL ATTITUDE: The diagnosis of urinary infection must be evidence-based, taking into account the patient's history and ruling out other diagnoses. In all cases, antibiotics must be carefully adapted to the patient's situation and titrated to kidney function. PMID- 11195836 TI - [Anti-epilepsy drugs and their use in the elderly]. AB - RISING INCIDENCE AND PREVALENCE: The frequency of epilepsy after the age of 60 years is increasing, a particularly important point in light of the rise in this age group. Incidence is estimated to exceed 100 cases per 100,000 subjects over the age of 60, reaching 160 per 100,000 in subjects aged 80 to 84 years. Prevalence exceeds 7 per 1000 in the 55 to 64 age group and 12 per 1000 in the 85 to 94 age group. CLINICAL FEATURES IN THE ELDERLY: Partial complex seizures are particularly frequent. Some patients experience seizure-related confusion states or slowly regressive neurological deficits. THERAPEUTIC STRATEGY: Excepting acute seizures induced by aggressive cerebral events, treatment should be aimed at the triggering factor. Anti-epilepsy drugs are warranted in patients who experience 2 or more seizures and for whom no amendable triggering factor can be identified. For stroke patients, long-term treatment should be reexamined after the acute phase. DRUG PRESCRIPTION: Benzodiazepines have proven efficacy when the objective is to achieve rapid control of frequent seizures. However, for elderly subjects, the risk of sedation and known adverse effects must be carefully assessed for these drugs. All anti-epilepsy agents are active: choosing the right drug for elderly subjects depends basically on patient tolerance and risk of drug interaction. Special attention should be given to the effect on cognitive function. PMID- 11195837 TI - [Diabetes in the elderly patient]. AB - EPIDEMIOLOGY: Diabetes mellitus in the elderly population is a major public health challenge. The aging population (over 65 years) now makes up 26.83% of the overall population in France and the prevalence of diabetes mellitus in this population is an estimated 10.3 to 20%. PATHOPHYSIOLOGY: The pathophysiology of diabetes is complex and mainly involves age-related insulin resistance. Changes in body fat, nutrition, and hormone secretions (insulin growth factor, dehydroepiandrosterone) also play an important role. Chronic hyperglycemia alone is pathogenic. COMPLICATIONS: Most are severe and induce not only dramatic vascular complications, diabetic foot, retinopathy, and neuropathy, but also, in association with age-induced illnesses and frail homeostasis, produce a high rate of disablement and decay of quality of life. MANAGEMENT: Current management of diabetes in the elderly population can be greatly improved. Systematic follow-up is essential, with special care to preserve self-independence. Education and self monitoring play an important role. Large diet allowances are recommended. Available drug therapies for the elderly (basically insulin, short half-life sulfamides, metformine if renal function in normal, and exceptionally alpha glucosidase inhibitors) must be examined in light of the specific situation of this frail population and the age-related changes in metabolism. Blood glucose control can be improved without risking unacceptable levels of hypoglycemia. PMID- 11195838 TI - [Treatment of arthroses in the elderly patient]. AB - BACKGROUND: Elderly subjects with osteoarthritis are treated with analgesic drugs, non-steroidal antiinflammatory drugs (NSAID) and intra-articular corticosteroid injections as well as symptomatic slow acting drugs in osteoarthritis (Sy-SADOA). BASIC REGIMENS: Initial treatment for osteoarthritis pain should be paracetamol, followed by NSAID if necessary, especially in the elderly, because of their adverse effects. EFFICACY: Sy-SADOA are effective on pain and function with a persistent effect, allowing the reduction of analgesic and NSAID dosage. PMID- 11195839 TI - [Dr. Watson's principle]. PMID- 11195840 TI - [Controlling pain in the elderly patient: efficacy and safety]. PMID- 11195841 TI - [Assessing nutritional status in the elderly: a different approach from assessing general health status]. PMID- 11195842 TI - [Protein-energy malnutrition. Diagnostic methods and epidemiology]. AB - EPIDEMIOLOGY: Protein-calorie malnutrition (PCM) is highly prevalent among elderly persons living in the community (4%), hospitalized in acute care units or geriatric rehabilitation units (50%), or in long-term care facilities (30-40%). PCM is the first predictor of poor prognosis in the elderly. DIAGNOSIS: Parameters used to establish the diagnosis of PCM and identify its pathophysiology are both simple and inexpensive: body mass index, plasma albumin and CRP, arm circumference and skin fold thickness. CONSEQUENCES: Because of its frequency and consequences on morbidity and mortality in the elderly, PCM is an important public health problem in industrialized countries. PMID- 11195843 TI - [Influence of nutrition and physical activity on muscle in the very elderly]. AB - AGE-RELATED LOSS IN MUSCLE MASS: Aging is associated with a progressive decline in muscle mass (sarcopenia). Age-related sarcopenia results in a 50% decrease in muscle fiber area, especially type II fiber area. There are many consequences related to this reduction in muscle mass including decline in muscle strength and function and impaired functional capacity. PROTEIN INTAKE: Sarcopenia also results in a reduction in the body's major protein pool. Adequate dietary protein to replace obligatory nitrogen loss and to support protein turnover is essential for maintaining muscle mass. It is usually suggested that protein requirements in older subjects are above 1 g/kg/d. PHYSICAL EXERCISE: Sedentary lifestyle may contribute to loss of skeletal mass in elderly people. Exercise can help reverse this deficit and may improve the regeneration potential of muscle fibers. PMID- 11195844 TI - [Malnutrition in the elderly. Clinical consequences]. AB - A COMMON PROBLEM: Undernutrition occurs when nutrient intake does not meet nutritional needs. Selective food intake induced micronutrient deficits (moderate undernutrition) and can later lead to protein calorie malnutrition (PCM). PCM is often discovered during acute illness (increased nutritional needs). PCM is observed in 30 to 50% of the institutionalized population and in 2-4% of the elderly living at home. Micronutrient deficits are far more frequent and concern 4 million elderly persons in France. AGE-RELATED CHANGES: Decreased smell and taste capacities and the inability to modify eating habits in stress conditions are mainly responsible for low food intake. Low intake leads to immunodeficiency, and subsequent frailty. Any intercurrent illness aggravates both undernutrition and immunodeficiency, creating a disease-to-disease spiral (undernutrition immunodeficiency) that is difficult to inverse. SIGNS OF PCM: Early signs of protein-calorie malnutrition are nonspecific: fatigue, apathy, decline in muscle strength. It is important to diagnose undernutrition at this stage before more specific symptoms develop: anorexia, weight loss, infection. Metabolic disorders occur at a later stage, generally during an acute illness, leading to overt PCM with perturbed glucose metabolism, recurrent infection, dehydration, impaired wound healing and calcium bone loss. The length of refeeding therapy depends on the intensity of the clinical signs, weight loss, dehydration, glucose metabolism disorder and/or on the severity of clinical complications such as infection or bone fractures. PRACTICAL ATTITUDE: Under nutrition must be recognized early at the stage of nonspecific clinical expression. Practitioners must be constantly aware of the risk of undernutrition and search for nonspecific signs in the elderly. PMID- 11195845 TI - [Nutritional support in elderly malnourished patients]. AB - ASSESSMENT OF NUTRITIONAL STATUS: Protein-calorie malnutrition is frequent and often severe in fragile hospitalized or institutionalized elderly subjects. Underdiagnosis and undertreatment is commonplace. Since under- or malnutrition is more difficult to correct in the elderly than in the young subject, a careful assessment of the nutritional status must be made in order to recognize any nutritional disorder early and initiate proper treatment early. NUTRITIONAL ASSISTANCE: High-protein oral supplementation and complementary enteral nutrition can improve the clinical status of certain under- or malnourished elderly subjects. It is particularly important to initiate nutritional assistance early and provide effective treatment for any recognized surgical or medical cause of malnutrition. Patient cooperation is crucial. EXPECTED RESULTS: Associated early with rehabilitation therapy, nutritional assistance can be expected to improve the functional independence of the elderly patient. Treatment efficacy and patient tolerance must be evaluated regularly to adapt nutritional assistance to the patient's particular clinical situation. Intensive enteral nutrition is not appropriate for elderly patients with severe malnutrition whose quality of life is compromised by motor, psycho-cognitive, or sensorial handicaps. PMID- 11195846 TI - Involvement of type I and type II mechanisms in the linoleic acid peroxidation photosensitized by tiaprofenic acid. AB - Analysis of the photomixtures resulting from irradiation of aqueous solutions of linoleic acid sensitized by tiaprofenic acid (TPA) or its major photoproduct (DTPA) by HPLC has shown the formation of all the four possible conjugated dienic hydroperoxides. According to laser flash photolysis experiments the rate constants for hydrogen abstraction from linoleic acid by the excited triplet states of TPA and DTPA are 2 x 10(5) and 3.2x 10(5) M(-1) s(-1), respectively. These data, together with the known rate constants for oxygen quenching of triplet (D)TPA and for the reaction of singlet oxygen with linoleic acid, show that the mechanism is mixed type I/type II. Finally, typical radical scavengers such as BHA and singlet oxygen quenchers such as DABCO and sodium azide are efficient quenchers of the triplet excited state of DTPA. This shows the risk of assigning mechanisms based on indirect 'evidences' using 'specific' additives. PMID- 11195847 TI - Photobinding of carprofen to protein. AB - Carprofen is a non-steroidal antiinflammatory drug with marked photosensitising properties. In order to elucidate the mechanisms underlying the phenomenon of drug-protein photobinding, mixtures of the drug and human serum albumin were irradiated under different experimental conditions. After irradiation and subsequent gel-filtration chromatography of the photomixture, the eluting protein fraction was analysed by means of fluorescence spectroscopy. The formation of drug-protein photoadducts could be evidenced by the characteristic emission properties of the carbazole chromophore. The photobinding of the drug to human serum albumin appears to involve the formation of aryl radicals resulting from carbon-halogen photocleavage. This mechanistic interpretation is supported by the observed variations in the intensity of the fluorescence spectra, which can be correlated with the lower quantum yield emission of chlorocarbazoles as compared to non-halogenated analogues. The results from laser flash photolysis studies are also in agreement with this proposal. PMID- 11195848 TI - Damage to mitochondria of cultured human skin fibroblasts photosensitized by fluoroquinolones. AB - The phototoxic fluoroquinolones ofloxacin, lomefloxacin, norfloxacin, ciprofloxacin and BAYy 3118 have ionizable groups with pKa values close to neutrality. Different ionic species of these fluoroquinolones, therefore, partition in various compartments and organelles of living cells according to their ionic equilibria. While all these fluoroquinolones accumulate in lysosomes, they more or less stain the rest of the cytoplasm of living HS 68 fibroblasts. As a result, photosensitized damage to other cytoplasmic sites than lysosomes can also be expected. Using microfluorometry and rhodamine 123 (Rh 123) as a specific fluorescent probe which is released from mitochondria by light absorption, we show that under ultraviolet A (UVA) irradiation norfloxacin and ciprofloxacin readily damage mitochondrial membranes. as evidenced by the UVA dose-dependent strongly accelerated release of Rh 123 from mitochondria in cells treated with norfloxacin and ciprofloxacin. Damages are already noticeable at UVA doses as low as 2 J/cm2. By contrast, no such photoinduced damage can be observed with ofloxacin, lomefloxacin and BAYy 3118, the latter being the most phototoxic derivative towards HS 68 fibroblasts. The initial photodamage induced by norfloxacin and ciprofloxacin can then propagate after the irradiation as shown by the strongly increased rate of release of Rh 123 from mitochondria of cells that have been incubated with these two fluoroquinolones and left in the dark after a pre-irradiation with 18 J/cm2 of UVA. Interestingly, the same pre irradiation after cells have been treated with BAYy 3118 and lomefloxacin induces similar post-irradiation effects, although they have no apparent immediate photosensitizing action on mitochondria. PMID- 11195849 TI - The phototumorigenic fluoroquinolone, lomefloxacin, photosensitises p53 accumulation and transcriptional activity in human skin cells. AB - The fluoroquinolone antibiotic, lomefloxacin, is phototoxic in human skin exposed to UVA radiation, photosensitises DNA strand breaks and pyrimidine dimers in human keratinocytes in vitro, and is phototumorigenic in mouse skin. The p53 tumour suppressor protein is activated by a variety of cellular insults including UV radiation, to become a transcription factor for downstream markers such as the cyclin-kinase inhibitor p21CIP1/WAF1 or cause caspase transactivation which cleaves poly ADP ribose polymerase (PARP) as an early step in apoptosis. We have investigated these molecular defence responses in human skin cells treated with lomefloxacin and UVA radiation in vitro. Western blots revealed that lomefloxacin photosensitised the stabilisation of p53 protein in human fibroblasts. Lomefloxacin also photosensitised p53 transcriptional activity in amelanotic melanoma cells expressing wild-type p53 and stably transfected with a construct containing a beta-galactosidase reporter gene downstream from a p53 consensus binding sequence. Neither photosensitised production of H2O2 nor the resultant DNA strand breaks, appeared to be involved in this effect. Interestingly, p21CIP1/WAFI protein was upregulated by lomefloxacin in the dark by a p53 independent mechanism. Lomefloxacin also photosensitised the degradation of nuclear PARP, suggestive of caspase mediated, early apoptotic events. PMID- 11195850 TI - Photoreactivity of tiaprofenic acid and suprofen using pig skin as an ex vivo model. AB - The skin is repeatedly exposed to solar ultraviolet radiation. Photoreaction of drugs in the body may result in phototoxic or photoallergic side effects. Non steroidal anti-inflammatory drugs, such as tiaprofenic acid (TPA) and the closely related isomer suprofen (SUP) are frequently associated with photosensitive disorders; they may mediate photosensitised damage to lipids, proteins and nucleic acids. Using ex vivo pig skin as a model, we investigated the photodegradation of TPA and SUP, and photobinding of these drugs to protein by means of HPLC analysis and drug-directed antibodies. Both with keratinocytes, which were first isolated from the pig skin and thereafter exposed to UVA and with keratinocytes which were isolated from pig skin after the skin was UVA exposed, time-dependent photodegradation of TPA and SUP was found, beside photoadduct formation to protein. The results of this work show that: (a) TPA and SUP were photodecomposed with similar efficiency; major photoproducts detected were decarboxytiaprofenic acid (DTPA) and decarboxysuprofen (DSUP), respectively. (b) Both drugs form photoadducts, as concluded from recognition by drug-specific antibodies. Pig skin appears to be a good model for studying the skin photosensitising potential of drugs. PMID- 11195851 TI - Photobinding of ketoprofen in vitro and ex vivo. AB - Ketoprofen (KP), a non-steroidal anti-inflammatory drug of the 2-aryl propionic class, has been shown to produce photoallergic side effects as well as cutaneous photosensitizing properties that induce other phototoxic effects. In the present study we investigated photobinding of ketoprofen to both human serum albumin (HSA), a model protein, and to ex vivo pig skin and its photodegradation. Results demonstrate that photoadduct formation and photodegradation progressively increased with irradiation time where they reach a maximum. Maximum photobinding to the viable layer of the epidermis was about 7-8% of the initial radiolabelled KP added, in the region of 15-30 min UV irradiation. These results were comparable to in vitro results that were seen with photobinding of KP to HSA; in this case, the quantity of covalently bound material was approximately 10% of the initial, after a maximum of 18 min irradiation. It was found by HPLC analysis that the KP decrease is accompanied by an increase of the corresponding photoproduct, decarboxylated ketoprofen (DKP). The yield of DKP reaches a maximum at around 15 min. DKP appears to play an important role in vitro and ex vivo, being the major photoproduct and responsible for the photobinding process. Using micro-autoradiographical techniques we investigated the penetration and distribution of ketoprofen in ex vivo pig skin in greater detail. It was apparent that percutaneous absorption was taking place and that most of the ketoprofen was predominately localised in fibroblasts in the papillary dermis. No other specific localisation within the skin architecture was identified. Although there were differences in the quantities of bound ketoprofen within the different layers of the skin, these levels did not appear to correlate with irradiation time. PMID- 11195852 TI - Analyses of cutaneous fluoroquinolones photoreactivity using the integrated model for the differentiation of skin reactions. AB - Currently available test models for the differentiation of photoallergic and photoirritant reactions are extremely time consuming and the protocols are very heterogeneous. In vitro tests are of proven value in predicting irritant or toxic effects, but these tests fail to predict chemical-induced allergic side effects. We developed test systems for this endpoint which is not easily detected by existing assays. In a previous publication we were able to discriminate between a contact sensitizer and a skin irritant with a combination of primary ear swelling analysis and cell counting of the ear-draining lymph nodes [Toxicol. Appl. Pharm. 153 (1998) 83; Arch. Toxicol. 73 (2000) 501]. This combination of tests was called the Integrated Model for the Differentiation of chemical-induced allergic and irritant Skin reactions (IMDS). In addition, it had been shown before that inclusion of UV irradiation in the local lymph node assay enables discrimination of photoallergic from photoirritant reactions after dermal application [Photodermatol. Photoimmunol. Photomed. 10 (1994) 57]. Because of the fact that fluoroquinolones are known to induce photoreactions after oral but not dermal treatment, the aim of the present study was to apply the IMDS for the fast and reliable differentiation of photoreactions due to fluoroquinolones after oral treatment. Enoxacin, lomefloxacin, ofloxacin, sparfloxacin and BAY y 3118 were tested in this system. We found a good correlation between the results of UV light-irradiated IMDS and a guinea pig model with the quinolones as far as photoirritancy was concerned. This holds true also for the photoallergic standard olaquindox and the photoirritant standard 8-methoxypsoralen. However, in contrast to the guinea pig assays the IMDS is fast and extremely predictive for the risk of both photosensitization and photoirritancy depending on the route of exposure. Thus, the UV light-irradiated IMDS turned out to be a good tool for the preclinical risk assessment procedure in terms of discriminating photoreactions. In addition, flow cytometric analyses were used to underline the fact that antigen-independent activation occurred after the induction of photoirritant reactions. PMID- 11195853 TI - Development of an expert system rulebase for the prospective identification of photoallergens. AB - Relationships between the structure and properties of chemicals can be programmed into knowledge-based systems such as DEREK (an acronym for 'Deductive Estimation of Risk from Existing Knowledge'). The DEREK knowledge-based computer system contains a sub-set of over 50 rules describing chemical substructures (toxophores) responsible for skin sensitization. This rulebase, based originally on Unilever historical in-house guinea pig maximisation test data, is largely complete and is undergoing refinement as the next stage of its development. As part of an ongoing program of validation and testing, the predictive ability of the sensitization rule set was assessed by processing the structures of over 100 chemical substances in the list of contact allergens identified by the BgVV (German Federal Institute for Health Protection of Consumers). The exercise highlighted areas of chemistry where further development of the rulebase was required, either by extension of the scope of existing rules or by generation of new rules where a sound mechanistic rationale for the biological activity could be established. Several chemicals likely to be acting as photoallergens were identified and rules for photoallergenicity were written covering three classes of chemicals. This paper describes work to extend the DEREK rules for photoallergenicity as part of the European Phototox Project. PMID- 11195854 TI - Photochemical decomposition of lomefloxacin in vitro and in vivo. AB - To obtain an idea of the photostability of Lomefloxacin (Lom) under in vivo conditions the compound was exposed to UV-A (310-360 nm) in PBS buffer pH 7.4. Exposure of 10 microg/ml of Lom in PBS pH 7.4 led to more than 50% decomposition within 10 min. Loss of the fluorine atom at C-8 and partial breakdown of the piperazine ring occurred. The only two photoproducts formed under these conditions were AEA, 1-ethyl-6-fluoro-1,4-dihydro-7-(2-aminoethyl-amino)-4-oxo-3 quinolinecarboxylic acid, and APA, 1-ethyl-6-fluoro-1,4-dihydro-7-(2-aminopropyl amino)-4-oxo-3-quinolinecarboxylic acid. When Lom was exposed in whole blood in vitro, the same photochemical decomposition was observed in the plasma as in PBS buffer: APA and AEA were the only products. During UV-A exposure, Lom was shown to be taken up by the leukocytes. This process appeared to be less rapid during UV-A exposure than in the dark. As soon as UV-A exposure commenced, AEA and APA were found. As in the plasma, the total amount of Lom and the two photoproducts in the leukocytes was not significantly different from the amount of Lom found in unexposed cells at the same time point. The erythrocytes did not take up Lom, but exposure of whole blood to Lom and UV-A under the above conditions led to more than 7% haemolysis. Treatment of rats with a combination of Lom and UV-A demonstrated photodecomposition of Lom in vivo. In urine produced during exposure and by the irradiated rats during the twilight period after exposure, a considerable amount of AEA and APA was found. The blood plasma from rats exposed simultaneously to UV-A and Lom proved to contain AEA and APA and, in the leukocytes, APA. This was not the case with animals kept in twilight. PMID- 11195855 TI - Clinical trials results of a unique monoclonal antibody in asthma. AB - IgE binds to high affinity receptors (Fc epsilon RI) on mast cells, basophils, alveolar macrophages, and antigen-presenting cells. This results in the degranulation of effector cells and the release of mediators, such as histamine, leukotrienes, cytokines, that are causally linked to the pathophysiology of allergic asthma. It made for an attractive target for the development of a unique humanized monoclonal antibody, rhuMAb-E25 (E25). E25 offers a novel strategic approach to allergy treatment, it is expected that using E25 to significantly decrease IgE levels will result in improved control of allergic asthma. PMID- 11195856 TI - Targets for asthma therapy. AB - Most asthma is allergic in origin, the disease involves four distinct phases of response: the sensitization phase and the activation phase, followed by the effector phase, initiated by the release of pharmacologically active agents, the growth and repair phase, characterized by proliferation of tissues as "remodeling" of the airway wall, altering structure and function. PMID- 11195857 TI - Varicose symptoms without varicose veins: the hypotonic phlebopathy, epidemiology and pathophysiology. The Acireale project. AB - Ever since 1982 the authors have been interested in varicose symptoms without varicose veins. Carrying out several pilot studies with infrared photoplethysmography (PPG) and strain gauge plethysmography they suggest that the pathophysiology of this behaviour could be caused by the reduction of the venous wall tone. They propose the name of Hypotonic Phlebopathy (HP). The diagnosis criteria are focused by symptoms (heavy legs in upright position, restless leg syndrome, sub-oedema and/or evening oedema) and signs detected by PPG, s.g plethysmography and duplex scanning (reduction of the muscle-venous calf pump and increase of the venous wall compliance). Epidemiology, assessed between 1989 and 1992 (Acireale Project), showed a 15.90% morbidity, with higher prevalence in females; the most important risk factors are pregnancy and family history. HP is not rare in males; the principal risk factor is work involving standing for long periods. These behaviours have been independently confirmed by two studies carried out in France in 1992, which showed a 15% prevalence in a similar group of subjects with functional venous insufficiency. The authors suggest the introduction of the term of Hypotonic Phlebopathy, the symptoms of which are significantly improved by phlebotonic drugs, especially when they are stronger. CEAP classification: C(0-S); E(P); A(0); P(unclassifiable); Clinical score (1-2); Anatomical score (0); Disability score (1). PMID- 11195858 TI - [Vascular pathology of surgical interest in drug addicts]. AB - The incidence of vascular complications due to drug abuse is at present increasing due to new types of drugs and to the different ways of intake of such substances. The vascular complications related to drug abuse may affect venous, arterious and lymphatic districts and in particular: ischemia following intra arterial injections, arterious and venous pseudoaneurysm, vasculitis, aneurysms, aortic dissections, abscesses complicated by erosions of vessels, arteriovenous fistulas, compartment syndrome, superficial and deep venous thrombosis, septic trombophlebitis, puffy hand syndrome. The scientific knowledge in this matter is incomplete because of the new pathological cases and the lack of information regarding the efficacy of different treatments. The authors report four patients affected by vascular pathologies due to drug abuse. In one case, a heroin addict has undergone multiple fasciotomies for compartimental syndrome arising because the patient maintained an innatural posture for several hours during an overdose coma. In a second case, a segmental right subclavear deep venous thrombosis has been treated by pharmacological therapy with satisfactory functional recovery of the arm. A third patient has been successfully submitted to intra-arterial pharmacological vasodilatation for generalised lower limbs vasospasm caused by drug abuse. In the last case, the voluntary swallowing of a great dose of cocaine caused the patient's death after multiple ischemic and hemorrhagic cerebral episodes. After the description of these cases, a review of the recent literature and some observations on this topic are presented. A better knowledge of vascular complications due to drug abuse should improve the therapeutical approach of these patients. PMID- 11195859 TI - [Harmonic echocardiography of tissue in the diagnosis of aneurysms of the interatrial septum. Study of 550 consecutive ambulatory patients]. AB - BACKGROUND: It has been assessed whether echocardiographic harmonic imaging improves the detection of atrial septal aneurysm (ASA) compared with fundamental imaging. METHODS: We studied consecutively, using fundamental and harmonic imaging, 550 patients (with or without cardiopathy; 300 females and 250 males) in an outpatients' department (age 23-76 years, mean 50 years). We used a multifrequency transthoracic probe transmitting at 2 Mhz and receiving at 4 Mhz. The ASA was classified in three types according to Hanley et al. Type 1A, protruding into the right atrium without oscillation; Type 1B protruding into the right atrium with oscillation, and Type 2, protruding into the left atrium with oscillation. We compared atrial septal aneurysm definition in fundamental and harmonic mode, and assessed the interobserver agreement in the diagnosis of ASA. The echocardiographic images were recorded on magneto-optical disk and analysed by two blinded observer. With Pearson test we assessed the interobserver concordance in the ASA study; so we quantified the advantage of harmonic imaging as reduction of the inter-observer variability. RESULTS: Among 550 consecutive subjects in the echocardiographic study population, ASA was diagnosed in 8 (1.45%) and 15 (2.72%) patients using fundamental and harmonic methods respectively. A significant reduction of the inter-observer variability in the ASA diagnosis was found with harmonic imaging (harmonic imaging: r = 0.96; fundamental imaging: r = 0.70). CONCLUSIONS: The harmonic methods drastically improves echocardiographic imaging of ASA, it may be used routinely and reduces the need for more invasive technique such as transesophageal echocardiography. PMID- 11195860 TI - [Use of colchicine in chronic pericardial effusion. Presentation of 2 clinical cases and review of the literature]. AB - Colchicine was introduced in 1987 for the treatment of recurrent pericarditis. Up to the present, papers have been published on a total of 117 patients treated with colchicine after the failure of treatment with FANS, corticosteroids and repeated pericardiocentesis. Here two cases of chronic pericardial effusion, one secondary to pericardiotomy, the second idiopathic, are reported. Both were recalcitrant to conventional therapy. Both patients were treated with 2 mg/die colchicine for 1 month followed by 1 mg/die for a further 5 months, without recurrence of the effusion after follow-up of 12 and 24 months respectively. No side-effects were observed. Colchicine is an anti-inflammatory drug which, by inhibiting various leukocyte functions, depresses the action of the leukocytes and of the fibroblasts at the site of the inflammation. We conclude that colchicine is effective in post-pericardiotomic and idiopathic chronic pericardial effusion as already reported in cases of recurrent pericarditis. Given the lack of side-effects, it could be considered as a drug of choice alternatively to FANS and corticosteroids. PMID- 11195861 TI - Thrombosis of mechanical valve prosthesis: thrombolysis vs surgical treatment. Report of two cases, personal experience and review of the literature. AB - We report the cases of two patients, previously operated for mitral mechanical valve replacement who developed thrombosis of the prosthesis. The two patients were successfully treated with pharmacological thrombolysis with no recurrence. One patient developed late peripheral embolization most probably due to late mobilisation of a thrombotic fragment. Our experience with surgical management is reported (39 mitral and 5 aortic prosthetic thrombosis from 1982 to 1999 among 89 patients with prosthetic malfunction). Average time interval between surgery and thrombus formation is 26 months (max 204, min 1 month). Rate of mitral thrombosis is 3.9% and aortic 0.25%. Clinical presentation spreads from almost asymptomatic patients to critically ill patients with pulmonary oedema or frank cardiogenic shock. Temporary suspension of anticoagulant therapy (83% in our study group) to rule out minor surgery, appears to be the most frequent cause of thrombosis. Transthoracic or better transoesophageal echo-cardiography and Doppler are by far the most accurate diagnostic tools that can entirely replace angiographic assessment. Operative mortality was 64% in the prosthetic mitral thrombosis and 20% in the aortic one. Thrombolytic treatment may be affected by minor to relevant complications such as peripheral or central embolization but in our experience and according to the literature it seems much less hazardous than re do surgery. Thrombolytic treatment is advocated for critical patients unless emergency institution of cardio pulmonary bypass is required and/or indicated. Re do surgery remains indicated for all other cases of prosthetic malfunction. PMID- 11195862 TI - Osteochondroma of the tibia and popliteal artery stenosis. AB - In our department, an osteochondroma of the tibia in a young girl with intermittent claudication of the right leg was treated. Many instrumental examinations were performed in order to exclude an arterial disorder. As the patient shows signs of arterial compression, an operative procedure to remove the exostosis was performed. PMID- 11195863 TI - Anaemia, osteogenesis imperfecta and valve diseases. The preoperative treatment with epoetin-alpha to increase haematocrit and haemoglobin levels in patients with high risk of perioperative bleeding. AB - The case of a patient with Osteogenesis imperfecta is reported who underwent surgery for mitral valve replacement. Osteogenesis imperfecta is a hereditary disease of the connective tissue, associated with bone fragility, bluish colouring of the sclerae, loss of hearing and dental anomalies. Osteogenesis imperfecta is included in a group of hereditary pathologies with Ehlers-Danlos syndrome, Hurler syndrome, pseudoxanthoma elasticum and Marfan syndrome. In the literature there are few cases of patients with osteogenesis imperfecta operated for mitral valve disease secondary to such disease. The patient also has a positive family history and a severe anaemia: this was treated with epoetin-alpha and ferrous sulphate during the three weeks before surgery. The response to epoietin treatment was good while clinical outcome was poor due to rupture of the posterior ventricular wall in the 12th postoperative hour. The use of epoietin alpha is discussed. PMID- 11195864 TI - Treatment of deep underlying reticular veins by Nd:Yag laser and IPL source. AB - BACKGROUND: The purpose of this paper is to estimate the efficacy of Nd:Yag laser and IPL combined action for the treatment of deep (up to 5 mm) and large (up to 3 mm in diameter) reticular varicosity of the lower extremity. METHODS: A group of 38 subjects (2 male and 36 female) aged from 34 to 65 years were treated for deep reticular varicosity of the legs. All patients underwent various clinical analyses in order to evaluate and exclude pre-existing cardiovascular pathology, coagulation disorders as well as pathology due to saphena incontinence. Also, for the first three months they underwent ambulatory specialistic treatments at 21 days intertreatment interval. RESULTS: A reduction of venous network of 80-90% after 2 treatment sessions with Nd:Yag laser was obtained in 84% of subjects. Successive 3 treatment sessions with IPL have achieved complete vanishing of the treated venous network in 36 patients (95%). CONCLUSIONS: A combined action of Nd:Yag laser and IPL has demonstrated its particular efficacy in non-invasive treatment of deep and extensive reticolar varicosity of the lower extremity, considering also that it is well tolerated by patients and applicable in each single case on out patient basis. PMID- 11195865 TI - Bone-inductive efficacy of recombinant human bone morphogenetic protein-2 expressed in Escherichia coli: an experimental study in rat mandibular defects. AB - Because to our knowledge the efficacy of prokaryotically expressed recombinant human bone morphogenetic proteins (rhBMP) to promote orthotopic osteogenesis has not previously been investigated, our aim was to test the efficacy of rhBMP-2 produced in Escherichia coli to promote bone healing in a standardised experimental bone healing model in rat mandibles. Different doses of rhBMP-2 were delivered in an absorbable collagen sponge carrier, and microporous barrier membranes were placed over half the number of defects in each treatment group, thereby making intraosseous cells the only recruitment source for new osteogenic cells. Results were evaluated by computerised image analysis after 12 and 24 days. The relative efficacy of rhBMP-2 preparations of different purity was also compared. E coli-produced rhBMP-2 stimulated bone healing, but its efficacy was estimated to be about one order of magnitude less than that of rhBMP-2 expressed in eukaryotic cells. We conclude that bacterially expressed rhBMP-2 is osteogenic in vivo, although higher doses will be required than of rhBMP-2 expressed in mammalian cell lines. PMID- 11195866 TI - Transfer of platelet-derived growth factor-BB gene by gene gun increases contraction of collagen lattice by fibroblasts in diabetic and non-diabetic human skin. AB - We have used an in vitro model of wound contraction, the fibroblast-populated collagen lattice, to examine the effect of platelet-derived growth factor BB (PDGF-BB) and PDGF-BB gene transfer by gene gun on the contraction of lattices composed of either diabetic or non-diabetic human fibroblasts. The area of collagen lattice and DNA synthesis were measured in 12 specimens. There were significant increases in lattice contraction with increasing doses of PDGF-BB and fibroblasts transfected with the PDGF-BB gene compared with control (p < 0.01). DNA synthesis of the non-diabetic and diabetic fibroblast lattices showed significantly increased incorporation of tritiated thymidine with increasing doses of PDGF-BB and fibroblasts transfected with the PDGF-BB compared with controls (p < 0.05). The effect of PDGF-BB gene transfer on diabetic and non diabetic fibroblasts was similar to that of 20 ng/ml or less of PDGF-BB. PMID- 11195867 TI - Scalding injuries in immigrant families. AB - From 1990 to 1996, 214 patients aged up to 6 years were treated at our inpatient burns unit. Ages ranged from 3 to 70 months. Scalding was the cause in 186 cases. The median size of the burned areas was 5.0% (range 0.5%-40%). One hundred and nine were deep dermal burns that required surgical treatment, but this was refused in seven instances. Duration of hospital stay was 11 days (2-45). The number of follow-up visits ranged from 0 to 17. Secondary reconstructions for scarring have been done for seven children so far. Ninety-eight (46%) came from immigrant families, mostly from the Middle East and the Balkans. Of the 186 scalded children, 94 (51%) were immigrants, and they also had a tendency to have more severe injuries. Explanations might be that they were more likely to cook with water and oil, they were unfamiliar with Swedish safety standards and measures, and they had difficulty in communicating (language) and a limited social network. The ensuing scar also may disturb or delay the child's adaptation to the new environment. Our preventive work is now based on a model that states that frequency, type, and severity of injury is dictated by the variables: risk, personality, supervision, and education. PMID- 11195868 TI - Wound closure by dermatotraction after fasciotomy for acute compartment syndrome. AB - Intramuscular pressure (IMP) was measured in 16 patients during secondary wound closure by dermatotraction with external tissue extension (ETE). Secondary wound closure was done 4-16 days after fasciotomy for acute compartment syndrome. The traction between wound edges was 2.5 N in the first six patients and 3.5 N in the following 10 patients. Mean (SD) IMP was 6.9 (3.5) mmHg before wound closure. It increased to 12.3 (1.4) mmHg in the 2.5 N group and to 24.7 (7.0) mmHg in the 3.5 N group when dermatotraction was applied. Mean (SD) leg perfusion pressure in the 2.5 N group decreased by 7% to 69.3 (10.9) mmHg and in the 3.5 N group by 23% to 62.2 (7.4) mmHg. None of the patients needed a skin graft. We conclude that dermatotraction by ETE raises IMP intraoperatively sufficiently to preserve adequate limb perfusion pressures. PMID- 11195869 TI - Dermabrasion of large congenital melanocytic naevi in neonates. AB - We describe our findings in a series of 12 patients with large congenital melanocytic naevi treated with dermabrasion between the first and fourteenth week of life. Postoperative follow-up ranged from 1-16 years. In all but two cases dermabrasion resulted in an appreciable and stable reduction of the hyperpigmentation, possibly by reducing the number of pigmented cells in the epidermis. In six of our 12 patients, reconstruction using grafts and flaps was done to improve the aesthetic result. Seven years after dermabrasion, one patient developed a minimal deviation melanoma in the treated area, but his subsequent clinical course has been uneventful. PMID- 11195870 TI - The lateral thoracodorsal flap in breast reconstruction: a comparison between two plastic surgical centres. AB - In a retrospective study the results of breast reconstruction with 146 lateral thoracodorsal flaps operated on during the period 1991-94 at the Departments of Plastic Surgery at the Sahlgrenska University Hospital in Goteborg and the Stockholm Soder Hospital were evaluated. The median age of the 135 patients was 51 years (range 37-74). About two thirds of the patients were also operated on on the opposite side at the same time; and this was done more often in Stockholm, which partly explains the longer operating time in Stockholm. Perioperative bleeding (median 100 ml, range 25-400) was similar in both groups. Median postoperative bleeding, which was measured only in Stockholm, was 300 ml (range 30-1000). Seromas were seen only in Goteborg where postoperative drains were rarely used. The rate of early complications (infection and partial necrosis) were higher in Stockholm where more flaps were raised in irradiated tissue. We conclude that the results were similar in the two centres, and the thoracodorsal flap gives good results. The incidence of early morbidity could be reduced by excluding patients who had been irradiated, by inserting drains, and by giving antibiotic prophylaxis. PMID- 11195871 TI - Clinical follow up of the lateral thoracodorsal flap in breast reconstruction: comparative evaluation from two plastic surgical centres. AB - A follow up study that compared the results from two plastic surgical centres comprised 95 patients after breast reconstruction with the lateral thoracodorsal (LTD) flap combined with either a smooth or textured saline-filled implant. It was conducted a median of 39 months (range 15-67) after the reconstruction. We investigated the size of the reconstructed breast and LTD flap, symmetry of the breasts, orientation of the mastectomy scar, and the rate of capsular contracture, which were similar in the two centres. However, according to the modified Baker classification and applanation tonometry reconstructions with smooth-surfaced implants and drainage of the implant pocket resulted in softer breasts (p = 0.03). The LTD flap technique in breast reconstruction was a good choice, particularly for women who required a minor breast reconstruction, and the technique can be recommended for suitable patients. PMID- 11195872 TI - Should sensory function after median nerve injury and repair be quantified using two-point discrimination as the critical measure? AB - Two-point discrimination (2PD) is widely used for evaluating outcome from peripheral nerve injury and repair. It is the only quantifiable measure used in the British Medical Research Council (MRC) classification that was developed by Highet in 1954. This paper reports the results of a study of 41 patients with complete median nerve lacerations to the wrist or forearm. Two-point discrimination thresholds were assessed together with locognosia (locognosia is the ability to localise a sensory stimulus on the body's surface), tactile gnosis, and touch threshold. Using the MRC classification 29 (71%) patients had a result of S2 or below, 11 (27%) were S3, and only one scored S3+. Patients scored much better on the other tests and showed progressive recovery. It remains too difficult for patients to obtain a measurable threshold value on 2PD and the test therefore lacks responsiveness. The rating of outcome from peripheral nerve repair should not be based solely on 2PD testing and must include other tests of tactile sensibility. PMID- 11195873 TI - Osseointegrated proximal interphalangeal joint prostheses with a replaceable flexible joint spacer--long-term results. AB - Osseointegrated proximal interphalangeal joint prostheses with a replaceable joint spacer were used in 25 joints in 19 patients (five men and 14 women) aged 45 (16-67) years. Indications for surgery were post-traumatic arthrosis (nine joints in eight patients), primary osteoarthrosis (10 joints in eight patients), and rheumatoid arthritis (six joints in three patients). A silicone joint spacer was attached to titanium fixtures by short titanium stems that extended from the spacer and fitted into a central canal in the screws. The arthroplasty was done in one stage, which included resection of the joint followed by grafting of marrow and cancellous bone from the iliac crest into adjacent medullary cavities before insertion of the titanium fixture. Follow up at 8.5 (5-11) years showed that 47 out of 50 fixtures (94%) had successfully osseointegrated while 17 of 25 joint spacers (68%) had fractured. However, because of the design of the prostheses fractured joint spacers could easily be replaced and a new spacer could be connected to already osseointegrated screws. The joint spacer was replaced in 11 fingers once or several times. Range of movement (ROM) in the whole series (four fusions excluded) was 41 (0-85) degrees with an extension defect of 15 (0-55) degrees. In eight joints with permanently intact joint spacers the ROM was 39 (0-60) degrees with extension defects of 16 (0-40) degrees. In six joints in which the spacer was replaced once the ROM was 43 (0 85) degrees with an extension defect of 16 (0-55) degrees. Our data confirm good long-term osseointegration of titanium fixtures and that a joint spacer, if needed, can be replaced by a new spacer that can be attached to already osseointegrated screws without jeopardizing the ROM. PMID- 11195874 TI - Triceps to biceps transfer to restore elbow flexion in three patients with brachial plexus palsy. AB - Between April 1994 and April 1998, triceps to biceps transfers were done for three men with post-traumatic lesions of the brachial plexus and consequent loss of elbow flexion. Their mean age at the time of their accidents was 33 years (range 19-41) and at the time of muscle transfer 40 years (28-46), with a mean observation period of 21 months (12-31). The transfer resulted in active elbow flexion in all patients with a mean of 113 degrees (90 degrees-130 degrees) and a degree of strength 4-5 (contraction against resistance) with no remaining deficit of passive extension. Two patients were satisfied with the result of the operation and the other was content. No complications were noted. The transfer of the triceps muscle to the tendon of the biceps muscle on loss of elbow flexion resulted in adequate movement and degree of strength. The triceps to biceps transfer involves operating close to the elbow joint and minimal complications, is cosmetically satisfactory, and is particularly suitable for co-contraction of triceps and biceps. PMID- 11195875 TI - Radial nerve palsy after simple fracture of the humerus. AB - Radial nerve palsy is a common complication of simple fracture of the humerus. The aim of this retrospective study was to assess the degree of spontaneous recovery and the need for exploration and repair of the nerve. The study included 26 patients with radial nerve palsy after simple fracture of the humerus. The male:female ratio was 3:1 and the median age was 21 years (range 9-79). Three patients had early exploration of the radial nerve in connection with osteosynthesis, and no appreciable damage to the nerve was found. Two other patients were explored later because they failed to recover. This exploration showed damage to the nerve which required further operation. Twenty-one patients were treated conservatively and all recovered well. None needed later operation. Because of the low incidence of nerve lesions we recommend an expectant policy initially. PMID- 11195876 TI - Effect of manual lymph drainage as described by Vodder on oedema of the hand after fracture of the distal radius: a prospective clinical study. AB - The aim of this study was to evaluate the efficacy of manual lymph drainage, as described by Vodder, in reducing oedema in the hand after a traumatic injury. During a period of 10 months in 1996-7, a total of 26 consecutive patients with a fracture of the distal radius that was treated by external fixation were included in the study. Patients were randomised into an experimental (n = 12) and a control group (n = 14). Treatment started 11 days after application of the external fixator. All patients had the same conventional treatment with exercises, movement, oedema control, and education. The experimental group was given 10 treatments of manual lymph drainage in addition. Oedema was measured four times with the volumeter, and the injured hand was always compared with the uninjured one. The first measurement was made three days after removal of the external fixation. The difference in hand volume showed that the experimental group had significantly less oedema in the injured hand. This result indicates that manual lymph drainage is a useful method for reducing post-traumatic oedema in the hand. PMID- 11195877 TI - Carpal tunnel syndrome in patients on long-term haemodialysis. AB - The purpose of this study was to describe the pathophysiology of carpal tunnel syndrome (CTS) in patients on long-term haemodialysis. We examined 110 patients, who had been having haemodialysis for chronic renal failure and had CTS, to clarify the clinical features and electrophysiological changes in peripheral nerves. There was a significant correlation between the incidence of CTS and the duration of haemodialysis. Compared with idiopathic CTS, CTS caused by long-term haemodialysis had relatively limited postoperative improvement. Symptoms recurred postoperatively in 11 patients (19%) of those with CTS caused by long-term haemodialysis. Electrophysiological measurements of sensory nerve conduction velocity showed that it was slower in distal segments of the median nerve in patients on haemodialysis compared with normal volunteers. Nerve conduction velocity in the carpal tunnel was significantly delayed (p < 0.05) in the patients with CTS on long-term haemodialysis. N9-13 interpeak latencies were significantly longer (p < 0.05) in subjects who had had haemodialysis for at least 10 years. All the patients with advanced destructive spondyloarthropathy had longer N9-13 interpeak latency. These results suggest that CTS in patients on long-term haemodialysis has its basis in neuropathy. The clinical course of CTS in these patients is different from that of patients with idiopathic CTS, because the neuropathy involves not only the carpal tunnel region, but also the proximal part of the median nerve both diffusely and progressively. PMID- 11195878 TI - Natural skin reduction and breast recovery using a tissue expander after enucleation of a giant breast tumour. AB - We report a new use of the tissue expander for reshaping a breast after resection of a giant tumour. After resection of giant fibroadenomas, two patients had expanders inserted into the tissue defect and gradually reduced in size over five months. This facilitated healing and natural skin shrinkage and resulted in a natural shape and size. PMID- 11195879 TI - Reconstruction of defects of the dorsum of the nose with bilateral transposition flaps. Case report. AB - Transposition flaps are old but are the method of choice in reconstruction of defects of the dorsum of the nose. Eleven consecutive patients with such defects were treated with 22 transposition flaps. The nasal defects resulted from tumour (n = 9), trauma (n = 1), and keratoacanthoma (n = 1). The dissection is rapid, easy and the complication rate is low. PMID- 11195880 TI - Hypertrophic branchial myopathy with uniform predominance of type 1 fibres. Case report. AB - A 17-year-old Japanese girl presented with left masseteric hypertrophy. She had a habit of chewing only on the affected side. Histochemical study of the masseter muscle showed myopathic changes characterised by uniform type 1 fibres with gross hypertrophy, increases of internal nuclei and split fibres, and endomysial fibrous tissue. This condition could be compatible with hypertrophic branchial myopathy, because it was confined to the masseter muscle and so cannot be classified into any known type of systemic myopathy. PMID- 11195881 TI - Giant cell tumour of the hamate. Case report. AB - We report the case of a 31-year-old woman who had had the distal end of the ulna resected for a giant cell tumour five years before presenting with a further one in the hamate. The medullary cavity of the hamate was curetted and cancellous bone grafted from the distal radius. Her symptoms resolved, and 26 months postoperatively the cortex of the hamate was fully restored. PMID- 11195882 TI - Median nerve injury caused by missed foreign body. Case report. AB - A 56-year-old woman sustained a delayed median nerve division after a penetrating injury of the right wrist by a piece of wood had gone unnoticed. There was no neurological damage at the time of the injury. The foreign body spread the median nerve apart, which subsequently reduced the sensitivity in the index finger. Removal of the wood resulted in complete recovery. PMID- 11195883 TI - Idiopathic tumoral calcinosis of the index finger. Case report. AB - Tumoral calcinosis of the hand is rare, and we present a case report of idiopathic tumoral calcinosis of the index finger, which posed a diagnostic problem as it looked like an infection. We successfully removed the calcific deposit and there had been no recurrence one year after the operation. PMID- 11195884 TI - Expressions of positive emotion in women's college yearbook pictures and their relationship to personality and life outcomes across adulthood. AB - To test hypotheses about positive emotion, the authors examined the relationship of positive emotional expression in women's college pictures to personality, observer ratings, and life outcomes. Consistent with the notion that positive emotions help build personal resources, positive emotional expression correlated with the self-reported personality traits of affiliation, competence, and low negative emotionality across adulthood and predicted changes in competence and negative emotionality. Observers rated women displaying more positive emotion more favorably on several personality dimensions and expected interactions with them to be more rewarding; thus, demonstrating the beneficial social consequences of positive emotions. Finally, positive emotional expression predicted favorable outcomes in marriage and personal well-being up to 30 years later. Controlling for physical attractiveness and social desirability had little impact on these findings. PMID- 11195885 TI - Sociocognitive self-regulatory mechanisms governing transgressive behavior. AB - This longitudinal research examined a structural model of the self-regulatory mechanisms governing transgressive conduct. Perceived academic and self regulatory efficacy concurrently and longitudinally deterred transgressiveness both directly and by fostering prosocialness and adherence to moral self sanctions for harmful conduct. The impact of perceived social self-efficacy was mediated through prosocialness. Moral disengagement and prosocialness affected transgressiveness through the mediating influence of irascible affectivity and hostile rumination. Ruminative affectivity, in turn, both concurrently and longitudinally affected transgressiveness. Moral disengagement also contributed independently to variance in transgressiveness over time. This pattern of relations was obtained after controlling for prior transgressiveness. The structural model was replicated across gender and provided a better fit to the data than did several alternative models. PMID- 11195886 TI - Age-related differences and change in positive and negative affect over 23 years. AB - Positive and negative affect, measured by the Bradburn Affect Balance Scale, were studied in a longitudinal sample spanning from 1971 to 1994. The sample (N = 2,804) represented 4 generations of families. Linear trend analyses compared generations over time for positive and negative affect and also examined the possible influences of neuroticism and extraversion on initial levels of affect and patterns of change in affect. Negative affect decreased with age for all generations, although the rate was attenuated among the oldest adults. Higher neuroticism scores also attenuated the decrease in negative affect across time. For positive affect, the younger and middle-aged adults showed marked stability, but the older group evidenced a small decrease over time. Higher levels of extraversion were related to more stability in positive affect. PMID- 11195887 TI - Self-concordance, goal attainment, and the pursuit of happiness: can there be an upward spiral? AB - Two studies used the self-concordance model of healthy goal striving (K. M. Sheldon & A. J. Elliot, 1999) to examine the motivational processes by which people can increase their level of well-being during a period of time and then maintain the gain or perhaps increase it even further during the next period of time. In Study 1, entering freshmen with self-concordant motivation better attained their 1st-semester goals, which in turn predicted increased adjustment and greater self-concordance for the next semester's goals. Increased self concordance in turn predicted even better goal attainment during the 2nd semester, which led to further increases in adjustment and to higher levels of ego development by the end of the year. Study 2 replicated the basic model in a 2 week study of short-term goals set in the laboratory. Limits of the model and implications for the question of how (and whether) happiness may be increased are discussed. PMID- 11195888 TI - Extending the bases of subjective attitudinal ambivalence: interpersonal and intrapersonal antecedents of evaluative tension. AB - Researchers have conceptualized ambivalence as resulting from the conflicting positive and negative thoughts and feelings that a person holds toward an attitude object (intrapersonal discrepancy). The authors investigated the hypothesis that perceived interpersonal attitudinal discrepancies can also contribute to feelings of subjective ambivalence beyond that determined by intrapersonal discrepancy. Study 1 revealed that the perception of attitudinal discrepancy with one's parents was associated with greater feelings of ambivalence. Studies 2 and 3 found increased ambivalence as a function of manipulated interpersonal discrepancies. Study 4 replicated and reversed the effect, revealing that interpersonal attitudinal discrepancy with a disliked other was associated with less ambivalence. Together, these studies provide support for the proposition that, because of balance processes, interpersonal relationships influence feelings of subjective ambivalence. PMID- 11195889 TI - Being accepted for who we are: evidence that social validation of the intrinsic self reduces general defensiveness. AB - Three studies examined the possibility that being liked intrinsically by others- for who one is--reduces self-esteem defense, whereas being liked for what one has achieved does not. All 3 studies contrasted the effects on self-esteem defense of liking based on intrinsic or achievement-related aspects of self. Study 1 showed that thoughts of being liked intrinsically reduced defensive bias toward downward social comparison. Study 2 demonstrated that being liked for intrinsic aspects of self reduced participants' tendency to defensively distance themselves from a negatively portrayed other. Study 3 revealed that being liked for intrinsic aspects of self encouraged a preference for upward over downward counterfactuals for a negative event. In all 3 studies, similar reductions in defensiveness were not found when liking was based on achievements. Discussion focuses on implications for understanding the functional value of different bases of self worth. PMID- 11195890 TI - Promotion and prevention focus on alternative hypotheses: implications for attributional functions. AB - Five studies examined hypothesis generation and discounting in causal attribution from the perspective of regulatory focus theory (E. T. Higgins, 1997, 1998). According to this theory, a promotion focus is associated with generating more and simultaneously endorsing multiple hypotheses, whereas a prevention focus is associated with generating only a few hypotheses and selecting 1 hypothesis from a given set. Five studies confirmed these predictions for both situationally induced and chronic individual differences in regulatory focus. In Studies 1, 2, and 3, individuals in a promotion focus generated more hypotheses than individuals in a prevention focus. In Studies 4 and 5, individuals in a promotion focus discounted explanations in light of alternatives less than individuals in a prevention focus. Study 5 also found that in a promotion focus, person explanations were generalized across situations less than in a prevention focus. PMID- 11195891 TI - Emotional distress regulation takes precedence over impulse control: if you feel bad, do it! AB - Why do people's impulse controls break down during emotional distress? Some theories propose that distress impairs one's motivation or one's ability to exert self-control, and some postulate self-destructive intentions arising from the moods. Contrary to those theories, Three experiments found that believing that one's bad mood was frozen (unchangeable) eliminated the tendency to eat fattening snacks (Experiment 1), seek immediate gratification (Experiment 2), and engage in frivolous procrastination (Experiment 3). The implication is that when people are upset, they indulge immediate impulses to make themselves feel better, which amounts to giving short-term affect regulation priority over other self regulatory goals. PMID- 11195892 TI - Emotions in collectivist and individualist contexts. AB - A theory of cultural differences in emotions was tested in a questionnaire study. Hypotheses about the differences between emotion in individualist and collectivist contexts covered different components of emotion: concerns and appraisals, action readiness, social sharing, and belief changes. The questionnaire focused on 6 types of events that were rated as similar in meaning across cultures. Participants were 86 Dutch individualist respondents and 171 Surinamese and Turkish collectivist respondents living in the Netherlands. As compared with emotions in individualist cultures, emotions in collectivist cultures (a) were more grounded in assessments of social worth and of shifts in relative social worth, (b) were to a large extent taken to reflect reality rather than the inner world of the individual, and (c) belonged to the self-other relationship rather than being confined to the subjectivity of the self. PMID- 11195893 TI - The forced-choice paradigm and the perception of facial expressions of emotion. AB - The view that certain facial expressions of emotion are universally agreed on has been challenged by studies showing that the forced-choice paradigm may have artificially forced agreement. This article addressed this methodological criticism by offering participants the opportunity to select a none of these terms are correct option from a list of emotion labels in a modified forced choice paradigm. The results show that agreement on the emotion label for particular facial expressions is still greater than chance, that artifactual agreement on incorrect emotion labels is obviated, that participants select the none option when asked to judge a novel expression, and that adding 4 more emotion labels does not change the pattern of agreement reported in universality studies. Although the original forced-choice format may have been prone to artifactual agreement, the modified forced-choice format appears to remedy that problem. PMID- 11195894 TI - Anger and advancement versus sadness and subjugation: the effect of negative emotion expressions on social status conferral. AB - Four studies examined status conferral (decisions about who should be granted status). The studies show that people confer more status to targets who express anger than to targets who express sadness. In the 1st study, participants supported President Clinton more when they viewed him expressing anger about the Monica Lewinsky scandal than when they saw him expressing sadness about the scandal. This effect was replicated with an unknown politician in Study 2. The 3rd study showed that status conferral in a company was correlated with peers' ratings of the workers' anger. In the final study, participants assigned a higher status position and a higher salary to a job candidate who described himself as angry as opposed to sad. Furthermore, Studies 2-4 showed that anger expressions created the impression that the expresser was competent and that these perceptions mediated the relationship between emotional expressions and status conferral. PMID- 11195895 TI - Interindividual-intergroup discontinuity reduction through the anticipation of future interaction. AB - Consistent with the role of a long-term perspective in reducing the tendency of intergroup relations to be more competitive than interindividual relations in the context of noncorrespondent outcomes, an experiment demonstrated that anticipated future interaction reduced intergroup but not interindividual competitiveness. Further results indicated that the effect was present only for groups composed of members high in abstractness (Openness-Intellect on the Big 5 Inventory and Intuition on the Myers-Briggs Type Inventory) who trusted their opponents. PMID- 11195896 TI - Suboptimal dialysis initiation in a retrospective cohort of predialysis patients- predictors of in-hospital dialysis initiation, catheter insertion and one-year mortality. AB - OBJECTIVE: Previous investigations using univariate study designs have reported that delayed referral to predialysis clinics is associated with adverse outcomes at the time of dialysis initiation. However, the independent effect of delayed referral is poorly defined. Moreover, the optimal time at which to refer patients to predialysis programs remains unclear. The aim of this study was to identify independent predictors of dialysis initiation requiring hospitalization. MATERIALS AND METHODS: A retrospective cohort of 201 predialysis patients was investigated using multivariate logistic regression analysis. RESULTS: Multivariate analysis selected advanced age (odds ratio (OR) 1.038,95% confidence interval (CI) 1.011-1.065), history of congestive heart failure (OR 2.877, 95% CI 1.205-6.871), and shorter predialysis follow-up time (OR 0.945, 95% CI 0.920 0.971) as independent predictors of in-hospital dialysis initiation. The risk of in-hospital dialysis initiation increased by 5.5% for every month lost due to late referral. CONCLUSION: Patients should be referred to predialysis programs as early as 24 months before anticipated dialysis initiation in order to minimize the risk of future adverse outcomes. PMID- 11195897 TI - Comparison of BTA stat and NMP22 tests in the detection of bladder cancer. AB - OBJECTIVE: This study aimed to compare the BTA (bladder tumour antigen) stat and urinary nuclear matrix protein (NMP22) tests in the detection of bladder cancer. MATERIAL AND METHODS: The office-based qualitative BTA stat and the laboratory based quantitative NMP22 tests were studied in the same urine samples obtained from 49 patients with a high suspicion of bladder cancer and 20 healthy subjects. RESULTS: A tumour was identified in 36 patients after the cystoscopy. BTA stat demonstrated a sensitivity of 89%, which was superior to the sensitivity of 66.6% with the NMP22 test in detecting the bladder cancer (p < 0.02). The sensitivities for grade I tumours with BTA stat and NMP22 were 55.5% and 33.3%, respectively. The sensitivity of BTA stat was 100% for tumour categories except for the pTa and grade I tumours. No positive result was observed with both tests among the healthy subjects. The specificities for BTA stat and NMP22 were 78.7% and 69.6%, respectively. CONCLUSIONS: The BTA stat test was significantly more sensitive than the NMP22 test in the detection of bladder cancer. Although the sensitivity of BTA stat was not sufficient to replace cystoscopy, its ease and low cost may play a role in reducing the number of control cystoscopies, especially in patients with low risk of progression. PMID- 11195898 TI - Evaluation of human leukocyte antigen expression in patients with prostate cancer. AB - OBJECTIVE: The aim of this prospective study was to evaluate the possible relationship between human major histocompatibility antigens [human leukocyte antigen (HLA)] and prostatic adenocarcinoma. MATERIAL AND METHODS: This clinical study was performed in 30 patients with histologically proven prostatic adenocarcinoma and 102 healthy men. HLA A, B and DR groups were evaluated in all patients. RESULTS: Of the HLAs examined, A2, A10, A28, A14, DR6, DR7 and DR9 were found to be accumulated significantly in patients with prostatic cancer in comparison with the healthy subjects. Apart from HLA A2 and DR7, the relative risk has been found to be over 2 in patients demonstrating these antigens. CONCLUSIONS: Although there was a statistically significant difference with respect to HLA accumulation between patients with prostate cancer and healthy subjects, larger series of patients including other parameters are needed. PMID- 11195899 TI - The use of betamethasone and hyaluronidase injections in the treatment of Peyronie's disease. AB - OBJECTIVE: The aim of this study was to assess the effect of local injections of betamethasone, hyaluronidase and lidocaine in patients with Peyronie's disease. MATERIAL AND METHODS: A total of 112 men who had a palpable plaque at the penis and suffered from painful erection and bending of penis was treated with a total of 12 injections containing betamethasone, hyaluronidase and lidocaine. Patients were classified into groups according to the duration of the disease (<6 months, 6-12 months or >12 months) as well as the size of the plaque (<10 mm, 10-20 mm or >20 mm). Pretreatment evaluation of patients and assessment of outcome were based on subjective criteria as well as measurement of the size of the plaque by means of ultrasound. Results were correlated to patients' characteristics. RESULTS: The overall response rate was 86%. Cure or improvement was noticed in 31% and 55% of patients respectively. Most of the patients (83%) had a duration of disease less than 12 months. Painful erection, bending of penis and plaque were absent in 97%, 32% and 31% of patients, respectively, after treatment. No severe complications were observed. The effect of treatment was strongly related to the duration of disease and the size of the plaque. CONCLUSIONS: The method is safe, well tolerated by patients and characterized by a high response rate in patients with a history of less than 12 months and a plaque not exceeding 20 mm. PMID- 11195900 TI - Effect of ultrasound in the treatment of primary nocturnal enuresis. AB - OBJECTIVE: This study aimed to determine the efficacy of ultrasound therapy in patients with primary nocturnal enuresis. MATERIAL AND METHODS: Thirty-five patients with enuresis were included the study. Patients were divided into two groups: 27 patients with enuresis were treated with ultrasound with irradiation and heating, and eight patients with enuresis were treated with ultrasound without irradiation or heating (placebo group). Ultrasound therapy was performed using the Therasonic 350 machine. The ultrasound therapy was applied to the skin of lumbosacral region. A treatment course of ultrasound comprised 10 sessions of 0.8 W/cm2 intensity applied daily for 8 min. Symptoms were evaluated I week, and 3, 6 and 12 months after the treatment. RESULTS: Twenty-two (81.5%) patients responded to the ultrasound therapy at the first week after the treatment. The effect of ultrasound started immediately after the treatment and continued during the 12 months of the follow-up period. CONCLUSION: Ultrasound therapy seems to be effective in the treatment of primary nocturnal enuresis in the 1 year follow-up period. PMID- 11195901 TI - First Scandinavian experience of electrical sacral nerve stimulation in the treatment of the overactive bladder. AB - OBJECTIVE: This study aimed to evaluate the efficacy of electrical sacral nerve stimulation (SNS) in the treatment of urinary incontinence and urinary retention refractory to conservative treatment, and to assess the impact of urodynamic abnormalities and electrode position. MATERIAL AND METHODS: Thirty patients (10 men, 20 women) with a mean age of 59 years (range 21-79 years), all of whom had longstanding symptoms ranging from 2 to 46 years (mean 12.4 years), were subjected to a percutaneous test stimulation. Ten patients responded well, resulting in a permanent implant in nine patients. Electrode positions were determined by plain X-ray and computed tomography. RESULTS: Radiologically, a variety of positions of the temporary electrodes was seen. In the implanted patients, long-term symptom reduction varied over time, ranging from total relief to partial or total recurrence of symptoms. CONCLUSIONS: SNS is a new promising option for the treatment of urge incontinence. Refined instruments for proper patient selection and the optimal way to position the electrode remain to be developed. PMID- 11195902 TI - Testicular seminoma in a man with bilateral microlithiasis and a history of cryptorchidism. AB - A case is presented of a young man with a history of bilateral cryptorchidism who presented with infertility. On investigation he was noted to have bilateral microlithiasis and left testicular seminoma. The possible association between microlithiasis and seminoma in patients with a history of cryptorchidism is discussed. PMID- 11195903 TI - An unusual case of duplex ureteropyelocystoplasty. AB - Ileocystoplasty is associated with electrolyte disturbances, mucus production and gastrointestinal tract disruption. An unusual case is presented of duplex ureteropyelocystoplasty with an excellent postoperative result. This technique avoids the complications associated with the use of ileum in the urinary tract. PMID- 11195904 TI - Erroneous diagnosis of chronic urinary retention in three women with pelvic cysts. AB - Three cases are presented where pelvic masses were originally misdiagnosed as cases of chronic urinary retention. In all cases the erroneous diagnosis was made at outpatient assessment, where postmicturition ultrasound scan measurement of residual urine volume had been performed. This investigation, while a useful tool, must be viewed in the context of other clinical findings. PMID- 11195905 TI - Rare earth elements--a new generation of growth promoters for pigs? AB - The present study which includes two feeding experiments was performed to investigate a possible performance enhancing effect of rare earth elements (REF) in piglets. This performance enhancing effect has been described in the Chinese literature for a long time, however, it was never tested under "western conditions". In the first feeding experiment 72 piglets at a mean BW of 7.3 kg were allotted to a control and to 4 REE groups at different levels of lanthanum chloride or an REE mixture containing mainly chlorides of lanthanum, cerium and praseodymium. The experimental period lasted 5 weeks. Positive effects of REE were found on body weight gain as well as on feed conversion ratio of the piglets. Compared to the control group, the daily weight gain was improved by 2 to 5% and feed conversion was better by up to 7%. These effects were, however, not significant. In the second feeding experiment, piglets (mean BW 17.3 kg) were fed for 8 weeks with a similar REE mixture. Significant positive effects of REE were found on both body weight gain and on feed conversion ratio by 19% and 10%, respectively. This is the first time that a performance enhancing effect of REE in pigs under western feeding conditions has been shown. Since the use of antibiotics as growth promoters in animal feed has been restricted in the European Union recently, rare earth elements might be of interest as new, safe and inexpensive alternative performance enhancers. PMID- 11195906 TI - Dietary carbohydrates affect caecal fermentation and modify nitrogen excretion patterns in rats. II. Studies with diets differing in protein quality. AB - In 2 two-factorial experiments, each conducted on 80 growing male rats, the effects of substituting 10% raw potato starch (PS), pectins (PEC), or cellulose (CEL) for wheat starch (WS) and the addition of tannic acid to WS (WSTA) were studied using diets differing in protein quality. Casein unsupplemented or supplemented with DL-methionine and gluten unsupplemented or supplemented with lysine, methionine and tryptophan were used as protein sources in Experiment 1 and 2, respectively. Parameters indicative of caecal fermentation intensity (pH, acetic, propionic and butyric acid contents, digesta and tissue weight) and of protein metabolism (urea blood concentration, faecal and urinary nitrogen excretion) were determined. Ten-day balance experiments were preceded by a 10-day adaption period to respective carbohydrates given in a diet containing balanced protein. In both experiments the type of carbohydrates affected the caecal concentration of individual and total SCFA and other parameters of fermentation intensity. Pectins and potato starch were fermented more intensively than cellulose. Faecal N excretion was increased by all carbohydrates substituted for cereal starch, and by tannic acid. Urinary excretion was greater on CEL than on PEC and WSTA containing casein and on other diets containing gluten. In both experiments urinary N excretion was the lowest on PEC diets. Protein quality had the greatest effect on apparent biological value and net protein utilization but all indices of protein utilization were also affected by carbohydrates. It is concluded that not only the amount of N excreted in faeces but also in urine is affected by the type and fermentability of carbohydrates. PMID- 11195907 TI - Comparative studies on the in vitro properties of phytases from various microbial origins. AB - The physical and chemical properties of six crude phytase preparations were compared. Four of these enzymes (Aspergillus A, Aspergillus R, Peniophora and Aspergillus T) were produced at commercial scale for the use as feed additives while the other two (E. coli and Bacillus) were produced at laboratory scale. The encoding genes of the enzymes were from different microbial origins (4 of fungal origin and 2 of bacterial origin, i.e., E. coli and Bacillus phytases). One of the fungal phytases (Aspergillus R) was expressed in transgenic rape. The enzymes were studied for their pH behaviour, temperature optimum and stability and resistance to protease inactivation. The phytases were found to exhibit different properties depending on source of the phytase gene and the production organism. The pH profiles of the enzymes showed that the fungal phytases had their pH optima ranging from 4.5 to 5.5. The bacterial E. coli phytase had also its pH optimum in the acidic range at pH 4.5 while the pH optimum for the Bacillus enzyme was identified at pH 7.0. Temperature optima were at 50 and 60 degrees C for the fungal and bacterial phytases, respectively. The Bacillus phytase was more thermostable in aqueous solutions than all other enzymes. In pelleting experiments performed at 60, 70 and 80 degrees C in the conditioner, Aspergillus A, Peniophora (measurement at pH 5.5) and E. coli phytases were more heat stable compared to other enzymes (Bacillus enzyme was not included). At a temperature of 70 degrees C in the conditioner, these enzymes maintained a residual activity of approximately 70% after pelleting compared to approximately 30% determined for the other enzymes. Incubation of enzyme preparations with porcine proteases revealed that only E. coli phytase was insensitive against pepsin and pancreatin. Incubation of the enzymes in digesta supernatants from various segments of the digestive tract of hens revealed that digesta from stomach inactivated the enzymes most efficiently except E. coli phytase which had a residual activity of 93% after 60 min incubation at 40 degrees C. It can be concluded that phytases of various microbial origins behave differently with respect to their in vitro properties which could be of importance for future developments of phytase preparations. Especially bacterial phytases contain properties like high temperature stability (Bacillus phytase) and high proteolytic stability (E. coli phytase) which make them favourable for future applications as feed additives. PMID- 11195908 TI - Lactational and metabolic effects in cows of lysine and methionine added to a ration deficient according to the I.N.R.A. method. AB - The effects of adding lysine and/or methionine to a ration of calculated deficiency in these amino acids of 10% and 20%, respectively, were studied in 24 Brown Swiss cows. The mixed rations (27% grass silage, 19% maize silage, 5% hay and 49% concentrate on DM basis) contained 14.5% CP on average. Lysine supply was selectively elevated by adding fish meal in exchange for other concentrate ingredients. Methionine was supplied in a rumen-protected form. Milk protein content was elevated whereas fat amount decreased by adding both amino acids. Lactose content increased without additional lysine from fish meal. Live weight, milk yield, milk fat content and protein amount remained unaffected by any variation of amino acids supply. Also nutrient digestibility and nitrogen balance were not changed by the treatments. Blood plasma concentrations confirmed the assumed variation in metabolic lysine and, less clear, methionine supply. Effects on plasma concentrations of other amino acids were relatively small. Most plasma hormones and enzymes, and metabolites in plasma, urine and milk did not respond to the variation in amino acid supply. Lysine addition via fish meal increased aspartate amino transferase and decreased urinary allantoin concentration. Additional methionine elevated plasma ornithine. Overall lysine and methionine appear to have been only marginally deficient in the unsupplemented ration fed for 3 weeks despite the deficiency of 10% to 20% as calculated by the I.N.R.A. method. PMID- 11195909 TI - Research note: is starch utilization for fat deposition in man different from that in animals? AB - Utilization of starch for fat deposition in humans was investigated by means of the nitrogen-carbon-balance method in a respiration chamber using the difference principle with a basal and a supplemental period. The basal diet was designed to maintain an adequate energy balance of the volunteer and to meet the maintenance requirements of protein, minerals and vitamins. The dietary fat content was minimized to 2.7% of DM. The digestibility of starch energy was determined to be 97%. The estimated efficiency of ME utilization of starch for energy deposition in humans amounted to 75.8%, which was in accordance with former results in pigs and rats. This suggests that in case of an intake of diets rich in carbohydrates and low in fat the utilization of carbohydrates for lipogenesis in humans is similar to that in monogastric mammal animals. PMID- 11195910 TI - Understanding ambiguous words in biased sentences: evidence of transient contextual effects in individuals with nonthalamic subcortical lesions and Parkinson's disease. AB - A cross-modal priming experiment was used to investigate lexical ambiguity resolution during sentence processing in individuals with nonthalamic subcortical lesions (NSL) (n = 10), compared to matched normal controls (n = 10), and individuals with cortical lesions (CL) (n = 10) and Parkinson's disease (PD) (n = 10). Critical sentences biased towards the dominant or subordinate meaning of a sentence-final lexical ambiguity were presented auditorily, followed after a short interstimulus-interval (ISI) (0 msec) or a long ISI (1000 msec), by the presentation of a visual target which was related to the dominant or subordinate meaning, or was an unrelated control word. Subjects made speeded lexical decisions on the targets. At the short ISI, lexical activation for the neurological patient groups appeared influenced by contextual information to a greater extent than in normal controls, which may indicate delayed lexical decision making or disturbed automatic lexical activation. At the long ISI, only the PD and NSL individuals failed to selectively activate the contextually appropriate meaning, suggesting a breakdown in the attention-based control of semantic activation through contextual integration. This finding may implicate disruptions to proposed frontal-striatal mechanisms which mediate attentional allocation and strategy formation. PMID- 11195911 TI - Emotional and physiological responses to false feedback. AB - The relationship between autonomic-visceral arousal and emotional experience is unclear. The attribution or cognitive-arousal theory of emotional experience posits that emotional experience is dependent on both visceral-autonomic nervous system feedback and the cognitive interpretation of the stimulus that induced this visceral activation. The finding that false cardiac feedback can alter emotional experience suggests that it may be the conscious perception that one is aroused, together with the cognitive interpretation of the stimulus that are important in developing emotional experience. Because the right hemisphere appears to play a special role in modulating arousal and interpreting emotional stimuli, it is possible that right hemisphere damage may interfere with developing the computations needed for emotional experience. To test this hypothesis we exposed men, both neurologically intact and those with right and left hemisphere lesions, to emotionally provocative pictures that were paired with false cardiac feedback, and examined the effects of this false feedback on their ratings of attractiveness of these pictures and their cardiac reactivity to this information. Subjects with left hemisphere damage, but not right hemisphere damage, showed significant changes in their emotional rating whereas control subjects showed marginal reactivity in their emotional ratings. Subjects with left hemisphere damage also showed significant changes in their cardiac reactivity. This finding is consistent with prior reports that indicate, when compared to right hemisphere damaged patients and normal controls, patients with left hemisphere lesions have an increased visceral-autonomic response to stimuli. These findings further provide support for the postulate that it is the cognitive interpretation of perceived physiological arousal together with the cognitive interpretation of the stimulus that is important in the development of emotional judgment and experience. These results do not support the approach-left hemisphere/avoidance-right hemisphere dichotomy, but instead suggest that left hemisphere damage increases reactivity to false feedback, and that the intact right hemisphere function integrates the cognitive interpretation of the emotional information and perceived arousal that lead to that emotional judgment. That these subjects showed no consistent relationship between their measures of cardiac reactivity and their ratings of attractiveness detracts from the James Lange and attribution theories. These subjects also showed no consistent relationship between their knowledge of affective physiological reactivity and their ratings of attractiveness, or between their knowledge of physiological reactivity and actual measures of cardiac reactivity, suggesting that other neuropsychological factors are involved in making an emotional judgment. PMID- 11195912 TI - An ecological approach to planning dysfunction: script execution. AB - Planning, which concerns many activities in everyday life, is a two-stage process. The first one predetermines a course of actions aimed at achieving some specific goals. It is founded on managerial knowledge or overlearned sequences of events and may be tested by script generation. The second stage entails monitoring and guiding the execution of the plan to a successful conclusion. It must take into account environmental contingencies and may be tested by script execution. If the frontal lobes intervene not only in managerial knowledge (Grafman, 1989) but also in binding the plan with contextual environment (Damasio, Tranel and Damasio, 1991; Shallice and Burgess, 1991), script execution would be more sensitive than script generation to planning deficits. To test this hypothesis, script execution and script generation were compared in 11 patients with a dysexecutive syndrome and 10 matched controls, using three scripts of daily life activities: (1) 'shopping for groceries'; (2) 'cooking'; (3) 'answering a letter and finding the way to post the reply'. Two way ANOVAs showed more errors in execution than in generation, more errors in patients than in controls, and a greater difference between execution and generation in patients than in controls. Furthermore, 'context neglect' and 'environmental adherence' were the two types of errors that best differentiated patients from controls. Finally, the total number of errors in execution correlated with the score on behavioral questionnaires answered by occupational therapists. These results confirm our hypothesis and suggest that script execution may be a valid ecological approach to estimate the severity of deficits in daily life activities. PMID- 11195913 TI - Orientation bias in unilateral neglect: representational contributions. AB - Left-neglect patients bisect horizontal lines to the right of true center. Longer lines are bisected further to the right than shorter lines. This line-length effect might be explained by an increase in the rightward bias of attention because longer lines extend further ipsilesionally. Alternatively, neglect patients might be limited in their abilities to internally represent horizontal magnitudes. Patients might orient further rightward with longer lines because these lines have longer representations. If the line-length effect occurs on lines of identical objective length but they are represented differently, then central mechanisms must contribute to the orientation bias. We constructed two types of lines that were perceived by normal subjects as having different lengths, but were of identical extents. Three neglect patients bisected lines perceived as longer, further to the right than lines perceived as shorter. These results demonstrate that relative magnitudes of internal representations contribute to the degree of bias in neglect patients. PMID- 11195914 TI - Predicting hand preference with performance on motor tasks. AB - Handedness may be defined as preference or hand-differences in task performance. The strength and significance of the relationship between hand preference and hand performance asymmetries have been contested. To evaluate this relationship, we administered the Edinburgh Handedness Inventory and measured asymmetries in finger tapping, Purdue Pegboard, and grip strength in 30 subjects who prefer their right hand and 30 subjects who prefer their left hand. Hand asymmetries in finger tapping, Purdue Pegboard, and grip strength each predicted hand preference scores. However, a multiple regression equation best predicted hand preference by using performance of each task. Hand asymmetries in finger tapping correlated strongly with asymmetries in Purdue Pegboard performance, but neither of these asymmetries correlated strongly with asymmetries in grip strength. These findings indicate that hand preference and asymmetries in motor proficiency are strongly related, but suggest that preference and proficiency for different aspects of motor performance may be independently lateralized. PMID- 11195915 TI - The role of the left hemisphere in verbal and spatial reasoning tasks. AB - Laterality of reasoning processes have long been a source of investigation. Differing formats of verbal and spatial reasoning tasks have meant it has not been possible to extricate true performance level from artefacts of input and output modalities. The Verbal and Spatial Reasoning Test (VESPAR) offers this opportunity, by virtue of matched sets of verbal and spatial inductive reasoning problems. Two series of 40 patients with unilateral left and right hemisphere lesions were tested on two verbal and two spatial subtests of the VESPAR, together with a battery of baseline tests. The performance of the left and right hemisphere lesion cases was compared with a normal standardisation sample. Whereas only the left hemisphere group failed the verbal sections, both left and right hemisphere groups failed the spatial sections. The influence of aphasia on spatial reasoning was considered to be an incomplete explanation for the failure of the left hemisphere group on the spatial sections. It is concluded that this investigation provides firmer evidence of a crucial role for the left hemisphere in both verbal and spatial abstract reasoning processes. PMID- 11195916 TI - Alzheimer patients' ability to read words with irregular stress. AB - The TIB, an Italian version of the National Adult Reading Test (NART), requires the subject to read out a list of Italian words with a dominant (regular) and a less frequent (irregular) stress pattern. It was given to a group of 45 patients with a diagnosis of dementia of Alzheimer type (DAT) and to a matched control group. Both the NART and the TIB are based on the assumption that the ability to translate orthography into phonology is relatively unimpaired in DAT patients. Despite the different language characteristics on which the two tests are based, the present results largely replicate those found for the NART. Patients with mild and moderate DAT did not perform differently from matched controls on the TIB, while they were impaired on the NART. Patients with severe dementia, however, also failed in the TIB test. PMID- 11195917 TI - Asymmetries of visuospatial attention are modulated by viewing distance and visual field elevation: pseudoneglect in peripersonal and extrapersonal space. AB - Many factors influence the degree of leftward error (pseudoneglect) that typifies the line bisection performance of normal subjects. We find that viewing distance also exerts a modulating influence on spatial attention in normal subjects, as it appears to do in neglect syndrome. Using forced-choice tachistoscopic line bisection, 38 right-handed subjects (15 male, 23 female) bisected horizontal lines (13.7 degrees w x 0.24 degrees h) presented in the midsagittal plane as a function of line elevation (- 3.6 degrees, 0 degrees, and 3.6 degrees relative to horizontal midline) and viewing distance (45 and 90 cm). We find a significant main effect of viewing distance, F (1, 37) = 10.04, p = .003, where pseudoneglect is larger in peripersonal (45 cm) than in extrapersonal (90 cm) space. We replicate an effect of line elevation, F (2, 74) = 4.40, p = .016, where pseudoneglect is greatest in the superior visual field (McCourt and Jewell, 1999). The interaction was not significant, p > .05. Thus, we find evidence for independent spatiotopic (viewing distance) and retinotopic (line elevation) effects on line bisection performance in normal observers, suggesting that the allocation of visuospatial attention is modulated within multiple frameworks. PMID- 11195918 TI - Semantic category dissociations, familiarity and gender. AB - We carried out four experiments to assess the extent to which familiarity with certain objects in everyday life is related to gender and can account, at least partially, for the semantic category dissociation observed in a few brain-damaged patients. In the first experiment, 210 normal subjects, half males and half females, were given the names of 60 stimuli from the Snodgrass and Vanderwart's set, 30 belonging to living categories and 30 to non-living categories. The task was to rate their familiarity, based on the frequency with which one (i) thinks or speaks of a given item, (ii) sees it represented in the media, and (iii) is confronted with real exemplars. The three indices were highly correlated and their average value was, therefore, used. Females gave higher familiarity ratings to fruit, vegetables and furniture and males to tools. The second experiment was aimed to verify whether the gender difference was responsible for the category dissociation found following brain damage. A male patient with greater impairment for living categories and a female patient with greater impairment for non-living categories were requested to name the same 60 stimuli and their scores were analysed, partialling out the familiarity effect, measured both with the non gender specific index of Snodgrass and Vanderwart and with the new gender specific index. In either case, the category dissociation remained significant. To determine if the mean general population familiarity index was valid for the single subject, we studied whether a cohabitant first degree relative was able to predict a normal subject's familiarity better than the population index. Contrary to expectations, the better predictor was the population index. The test-retest reliability of each subject's familiarity ratings was satisfactory, but not higher than the correlation between the personal judgement of each subject and the population index. PMID- 11195919 TI - Cinema seating in right, mixed and left handers. AB - Two hundred and sixty four right-handed, 246 mixed-handed and 360 left-handed students were requested to indicate on five maps of cinema halls what place they would choose. All three handedness groups showed a preference for the right and a corresponding directional bias towards the left space. However, they differed significantly from each other on the magnitude of this bias which was most pronounced in right and less in left handers. It is assumed that lateralized mechanisms underlying such biases have developed evolutionarily and serve right handed persons best. Non-dextrality considerably reduces their phenotypic expressions, but even left-handedness does not reverse the directional bias towards the left. It is also hypothesized that right, mixed and left handers differ in a large number of behavioral choices and strategies, modeled by cerebrally lateralized mechanisms and that the cinema seating preference is only one of them. PMID- 11195920 TI - [Risk management in the surgical practice: recovered serenity]. PMID- 11195921 TI - [Role of somatostatins in the preventin of pancreatic fistulae and the treatment of digestive fistulae]. AB - Somatostatin and analogues exert an extraordinary range of inhibitory effects which eventually may have a variety of therapeutic applications. Treatment of intestinal and pancreatic fistula are the main targets in general and digestive surgery. The perioperative and prophylactic application of somatostatin or octreotide in patients who undergo major pancreatic surgery reduces the postoperative complication rate. This prevention seems indicated following Whipple procedure in patients with soft pancreatic tissue. The efficacy of somatostatin or analogues in the treatment of intestinal or pancreatic fistulae is still in debate. Fistula output frequently decreases but closure rate, healing time and complications rate are not reduced. The treatment and care of patients with high output fistulae may be simplified by somatostatin or analogues if a positive effect on output is obvious in the first days of treatment. PMID- 11195922 TI - [French randomized trials in general and digestive surgery in the last decade]. AB - STUDY AIM: To study the characteristics of randomized trials published by general and digestive French surgeons over the last decade. MATERIAL AND METHODS: An extensive electronic and manual literature search was performed. Trials published as original articles compared two surgical techniques or a surgical procedure with a nonsurgical treatment. The characteristics of the trials and their methodology were assessed. At the same time, a survey was conducted among authors to assess the impact of application of the Huriet-Serusclat law (ethics related to the protection of individuals subjected to bioclinical research) on the conduct of the trial. RESULTS: Forty trials (including 22 multicentre trials) were found. Twelve trials (30%) addressed a key-question and twenty (50%) addressed a particular step of the procedure (anastomosis, drainage, etc). Most trials (83%) were published in English language journals. The 18 trials with a good methodological quality mainly had a multicentre design (n = 16). The survey showed that 10 trials were conducted prior to the publication of Huriet-Serusclat law and that 14 trials were conducted in compliance with this law. CONCLUSION: This study revealed the large number of well designed multicentre trials in France. But most trials assessed technical steps of the surgical procedures. Application (without prerequisite) of the Huriet-Serusclat law could probably explain the rarity and the difficulties of conducting trials comparing two different procedures or a surgical with a medical treatment. PMID- 11195923 TI - [Laparoscopic treatment of solid and cystic tumors of the liver. Study of 33 cases]. AB - AIM OF THE STUDY: Laparoscopic liver surgery is still in its early stages. The aim of this study was to report our experience in the laparoscopic management of solid and cystic liver tumours. PATIENTS AND METHODS: From April 1991 to December 1999, 32 patients with various lesions of the liver underwent laparoscopic liver surgery. One group of patients presented with cysts (n = 15) (11 giant solitary cysts and 4 polycystic liver diseases) and one group of patients presented with solid tumours (n = 18): focal nodular hyperplasia (n = 8), haemangioma (n = 6), adenoma (n = 2), isolated metastasis from a colonic cancer (n = 1) and hepatocellular carcinoma (n = 1). Fifteen cyst fenestrations and eighteen liver resections were performed via a laparoscopic approach including 1 right lobectomy, 5 left lateral segmentectomies, 2 subsegmentectomies IVb, 1 segmentectomy III and 9 non-anatomical resections. RESULTS: Conversion to laparotomy was performed in one case (3%) at the end of the operation (patient who had successfully undergone left lateral segmentectomy for hepatocellular carcinoma) to check the resection margins and surgical transection had been performed in healthy parenchyma. Mean diameter of solid tumours was 6.5 cm and 15.7 cm for solitary cysts. The mean operating time for hepatic resections was 232 minutes. There was no postoperative mortality. Complications occurred in one case for each group and consisted in intestinal stricture through a port site requiring intestinal resection. Mean postoperative hospital stay was 5.6 days for solid tumours and 7.5 days for cystic lesions. In the group of cystic lesions, the recurrence rate was 50% with a 5.5-months follow-up. CONCLUSION: Laparoscopic liver surgery can be safely performed, but requires a good experience in open hepatic surgery and laparoscopic surgery. The laparoscopic approach is indicated in patients with symptomatic or atypical benign solid tumour, giant solitary cyst and polycystic liver disease, located anteriorly on the liver. Indications for malignant lesions have not been clearly defined and require further information. PMID- 11195924 TI - [Assessment of quality of life after antireflux surgery]. AB - AIM OF THE STUDY: To assess the quality of life (QoL) of patients operated for gastroesophageal reflux disease (GERD). PATIENTS AND METHODS: This prospective study included 82 consecutive patients submitted to antireflux surgery between October 1998 and January 1999. A new questionnaire was used to assess their QoL: the Gastrointestinal Quality of Life Index (GIQLI) that includes 36 items concerning 5 dimensions: symptoms, vitality, emotions, social relations and medical treatment. The series consisted of 44 men and 38 women with a mean age of 47 years (range: 18-78). QoL was assessed before and 6 months after surgery; the follow-up rate was 94% (77/82). The pre- and postoperative GIQLI scores of the study group and the GIQLY score of a control group of 110 healthy patients were compared. RESULTS: Before surgery, the GIQLI score (90 +/- 23) was greatly impaired compared to the score (123 +/- 13) observed in the control group (p < 0.001). After surgery, the GIQLI score (110 +/- 23) increased significantly (p < 0.001), but remained statistically lower than the score of the control group (p < 0.001). The postoperative score recorded in the symptoms dimension was lower than the control group score: 55 +/- 11 versus 66 +/- 6 (p < 0.001), while no significant difference was observed in the other 4 dimensions. Univariate statistical analysis revealed that the postoperative GIQLI score (y) was correlated with the preoperative GIQLI score (x) according to the formula: y = 0.43 x + 71 (p < 0.001) and the sex of the patients, as the postoperative GIQLI score was higher in male patients (115 +/- 19) than in female patients (103 +/- 23) (p < 0.02). CONCLUSION: The QoL of the patients was greatly improved after antireflux surgery, but remained lower than that of a control group of healthy subjects. Better patient selection should improve the results. In our series, male patients or patients with a high preoperative GIQLI score were the best candidates for antireflux surgery. PMID- 11195925 TI - [Pickrell intervention in children for anal incontinence secondary to anorectal malformation]. AB - STUDY AIM: The aim of this study was to report the results of unilateral Pickrell procedure in children with fecal incontinence secondary to anal atresia. PATIENTS AND METHOD: Twenty three children were operated between 1975 and 1997. The mean age at the time of the operation was 8.5 years. Functional results were systematically evaluated by Kelly's clinical score and by anal sphincter electromyography and anal manometry for some patients. RESULTS: There was no postoperative mortality. One colostomy was performed for recurrent local sepsis. The functional result with a mean follow-up of 6 years was estimated to be good in 25%, intermediate in 45% and poor in 30%. Clinical improvement of continence was obtained in 70% of cases. CONCLUSION: The improvement of continence after Pickrell procedure essentially depends on the patient selection criteria, pre- and postoperative rehabilitation and regular enemas. In the case of poor results, the authors propose bilateral Pickrell procedure which improved the results in eight out of nine children in this group. PMID- 11195926 TI - [Intravagal parathyroid ectopia]. AB - AIM OF THE STUDY: The presence of an ectopic parathyroid gland is the commonest cause of persistent hyperparathyroidism (HPT). High cervical ectopic glands represent 0.21 to 9% of these cases. Only 3 cases of high intravagal sites have been described. The authors report two new cases of persistent HPT caused by an intravagal parathyroid gland. PATIENTS AND METHOD: In a series of 1,712 cases of HPT operated over the last 25 years (1,307 primary HPT and 405 secondary or tertiary HPT), two cases (0.12%) of persistent HPT were caused by a high intravagal parathyroid gland. One case corresponded to primary HPT and the other case corresponded to tertiary HPT. One patient underwent three operations and the other patient underwent four operations. CONCLUSION: Intravagal thyroid tissue may cause HPT. This very rare site must be considered among the other high cervical ectopic sites in the pre- and intraoperative assessment of hyperparathyroidism, particularly in cases of persistent or recurrent hyperparathyroidism. PMID- 11195927 TI - [Mature teratome of the mediastinum]. AB - STUDY AIM: The aim of this retrospective study was to report a series of 12 cases of mature teratoma of the mediastinum operated during a 10-year period in the same center. PATIENTS AND METHOD: From 1990 to 2000, 12 patients (7 females and 5 males with a mean age of 32 years) were operated for mature mediastinal teratoma. Chest pain was present in 10 cases; cough, dyspnea and septic episodes were present in 5 cases and X-ray detected the mediastinal tumor in 10 cases. CT scan showed a tumor with liquid and fatty components and calcifications in 5 out of 9 cases. Tumors were resected via a posterolateral thoracotomy in 11 cases and an anterior thoracotomy in one case, associated with pneumonectomy in 1 case, basal segmentectomy in 1 case and thymectomy in 1 case. RESULTS: There were no postoperative deaths. Morbidity included 2 phrenic nerve palsies, 1 pyothorax after pneumonectomy, 1 case of bleeding and 1 pleural effusion. No recurrences have been observed with a follow-up of 5 to 87 months. Nine of the 10 tumors reviewed by pathologist contained multiple tissue components and one only contained a single tissue. CONCLUSION: Mature teratomas are usually detected in young patients: they are usually located in the middle part of the anterior mediastinum and are only diagnosed by pathologic examination of the specimen. They have an excellent prognosis when tumor resection is complete and in the absence of immature tissue in the tumor. PMID- 11195928 TI - [Filling of bone defects with tricalcium phosphate beta in traumatology]. AB - AIM OF STUDY: Synthetic bone substitutes like calcium phosphate ceramics have been used in orthopaedic surgery for several years. The aim of this study was to assess the results of the use of tricalcium phosphate beta for filling bone defects in trauma cases. PATIENTS AND METHOD: beta tricalcium phosphate was used in 24 trauma cases. The GESTO classification (Association pour l'etude des Greffes et Substituts Tissulaires en Orthopedie) and a qualitative scale were used to estimate the integration. RESULTS: With a mean follow-up of 20 months, integration was excellent in 41.2%, good in 29.2% and moderate in 17.4%. No fibrous encapsulation was observed around the implants in any case. Sepsis occurred in 3 cases with open fractures. CONCLUSION: beta-Tricalcium phosphate seems in our experience to be an excellent bone substitute for filling bone defects in trauma cases. PMID- 11195929 TI - [Use of the vacuum-assisted closure system for the treatment of perineal gangrene involving the abdominal wall]. AB - The vacuum-assisted closure (VAC) system is used for the treatment of complicated wounds and large tissular dehiscences. The study aim was to report a case of perineal gangrene extended to the abdominal wall in a 53-year old woman. After several extensive surgical debridments, using of the VAC was followed by a good and rapid healing of the wound. PMID- 11195930 TI - [Primary malignant melanoma of the esophagus]. AB - Primary malignant melanoma of the esophagus is a rare but aggressive tumor that accounts for less than 0.1-0.2% of all esophageal malignancies. The aim of this study was to report a case of primary malignant melanoma of the esophagus in a 72 year-old woman. The diagnosis was histologically proven, but the patient died despite extensive surgical resection. PMID- 11195931 TI - [Germain Pichaut de Lamartiniere. Eulogy presented to the Royal Academy of Surgery during the public session on April 22, 1784]. AB - G. Pichaut de Lamartiniere (1696-1783) accompanied the king during his campaigns and, in 1747, then succeeded La Peyronie as first surgeon to the king and President of the Royal Academy of Surgery. "He devoted his talent as an organizer in favour of surgeons. He did everything to proclaim the independence of surgery and to protect it from the tyranny of the Faculty of Medicine of Paris". He did not leave behind any scientific or academic works. PMID- 11195932 TI - The nuclear chloride ion channel NCC27 is involved in regulation of the cell cycle. AB - NCC27 is a nuclear chloride ion channel, identified in the PMA-activated U937 human monocyte cell line. NCC27 mRNA is expressed in virtually all cells and tissues and the gene encoding NCC27 is also highly conserved. Because of these factors, we have examined the hypothesis that NCC27 is involved in cell cycle regulation. Electrophysiological studies in Chinese hamster ovary (CHO-K1) cells indicated that NCC27 chloride conductance varied according to the stage of the cell cycle, being expressed only on the plasma membrane of cells in G2/M phase. We also demonstrate that Cl- ion channel blockers known to block NCC27 led to arrest of CHO-K1 cells in the G2/M stage of the cell cycle, the same stage at which this ion channel is selectively expressed on the plasma membrane. These data strongly support the hypothesis that NCC27 is involved, in some as yet undetermined manner, in regulation of the cell cycle. PMID- 11195933 TI - Regulation kinetics of Na+-Ca2+ exchange current in guinea-pig ventricular myocytes. AB - To investigate the regulation of native cardiac Na+-Ca2+ exchange by cytoplasmic Na+ (Na+i) and Ca2+ (Ca2+i), we recorded the Na+-Ca2+ exchange current (INa-Ca) from inside-out 'macro patches' excised from intact guinea-pig ventricular cells. The half-maximal concentration (Kh) of Ca2+i required to induce an inward INa-Ca was 7 microM. The Kh of Na+i required to induce an outward INa-Ca was 21 mM, and tended to decrease at the steady state of Na+-dependent inactivation. The time constant (tau) of Na+-dependent inactivation was approximately 1.5 s at 100 mM Na+i and 1 microM Ca2+i. The Kh for Na+i was 14 mM. Ca2+i augmented the peak outward INa-Ca (Kh = 0. 2 microM) and attenuated Na+-dependent inactivation (Kh = 2.2 microM). The outward INa-Ca was activated by 5 microM Ca2+i with a half-time to reach steady state (t1/2) of approximately 0.4 s. This activation was composed of two exponential processes. Deactivation of the current upon Ca2+i removal also consisted of two exponential processes and had a t1/2 of approximately 0.5 s. A Na+-Ca2+ exchange model, consisting of one consecutive 4Na+:1Ca2+ exchange cycle and two inactive states, well mimicked the experimental data with regard to ion dependencies and regulation kinetics. These data provide detailed information on the kinetics of the Na+i- and Ca2+i-dependent regulation of native Na+-Ca2+ exchange. They also indicate that the regulation kinetics operate faster in macro patches than in the giant membrane patch from cardiac 'blebs', or in Xenopus oocytes expressing a cloned exchanger (NCX1.1). PMID- 11195934 TI - A genetic algorithm with adaptive mutations and family competition for training neural networks. AB - In this paper, we present a new evolutionary technique to train three general neural networks. Based on family competition principles and adaptive rules, the proposed approach integrates decreasing-based mutations and self-adaptive mutations to collaborate with each other. Different mutations act as global and local strategies respectively to balance the trade-off between solution quality and convergence speed. Our algorithm is then applied to three different task domains: Boolean functions, regular language recognition, and artificial ant problems. Experimental results indicate that the proposed algorithm is very competitive with comparable evolutionary algorithms. We also discuss the search power of our proposed approach. PMID- 11195935 TI - Short-term prediction of chaotic time series by using RBF network with regression weights. AB - We propose a framework for constructing and training a radial basis function (RBF) neural network. The structure of the gaussian functions is modified using a pseudo-gaussian function (PG) in which two scaling parameters sigma are introduced, which eliminates the symmetry restriction and provides the neurons in the hidden layer with greater flexibility with respect to function approximation. We propose a modified PG-BF (pseudo-gaussian basis function) network in which the regression weights are used to replace the constant weights in the output layer. For this purpose, a sequential learning algorithm is presented to adapt the structure of the network, in which it is possible to create a new hidden unit and also to detect and remove inactive units. A salient feature of the network systems is that the method used for calculating the overall output is the weighted average of the output associated with each receptive field. The superior performance of the proposed PG-BF system over the standard RBF are illustrated using the problem of short-term prediction of chaotic time series. PMID- 11195936 TI - Kernel and nonlinear canonical correlation analysis. AB - We review a neural implementation of the statistical technique of Canonical Correlation Analysis (CCA) and extend it to nonlinear CCA. We then derive the method of kernel-based CCA and compare these two methods on real and artificial data sets before using both on the Blind Separation of Sources. PMID- 11195937 TI - Features selection and architecture optimization in connectionist systems. AB - In this paper, we propose a features selection measure and an architecture optimization procedure for Multi-Layer Perceptrons (MLP). The algorithm presented in this contribution employs a heuristic measure named HVS (Heuristic for Variable Selection). This new measure allows us to identify and select important variables in the features space. This can be achieved by eliminating redundant features and those which do not contain enough relevant information. The proposed measure is used in a new procedure aimed at selecting the "best" MLP architecture given an initial structure. Application results for two generic problems: regression and discrimination, demonstrates the proposed selection algorithm's effectiveness in identifying optimized connectionist models with higher accuracy. Finally, an extension of HVS, named epsilonHVS, is proposed for discriminative features detection and architecture optimization for Time Delay Neural Networks models (TDNN). PMID- 11195938 TI - Assessing rbf networks using DELVE. AB - In this paper, different methods for training radial basis function (RBF) networks for regression problems are described and illustrated. Then, using data from the DELVE archive, they are empirically compared with each other and with some other well known methods for machine learning. Each of the RBF methods performs well on at least one DELVE task, but none are as consistent as the best of the other non-RBF methods. PMID- 11195939 TI - Content-based image retrieval system using neural networks. AB - An effective image retrieval system is developed based on the use of neural networks (NNs). It takes advantages of association ability of multilayer NNs as matching engines which calculate similarities between a user's drawn sketch and the stored images. The NNs memorize pixel information of every size-reduced image (thumbnail) in the learning phase. In the retrieval phase, pixel information of a user's drawn rough sketch is inputted to the learned NNs and they estimate the candidates. Thus the system can retrieve candidates quickly and correctly by utilizing the parallelism and association ability of NNs. In addition, the system has learning capability: it can automatically extract features of a user's drawn sketch during the retrieval phase and can store them as additional information to improve the performance. The software for querying, including efficient graphical user interfaces, has been implemented and tested. The effectiveness of the proposed system has been investigated through various experimental tests. PMID- 11195940 TI - Effects of background noise on audiometric thresholds during positron emission tomography: passive and active noise-reduction. AB - Position emission tomography (PET) is used to assess the functional activity of the human auditory brain; however, the activity detected by PET could be affected by ambient acoustic noise from the PET equipment. To evaluate these effects, we compared behavioural thresholds in the PET camera with those measured in an audiometric sound booth. Thresholds were measured with: (i) ER2 earphones, (ii) ER2 earphones + Cabot earmuffs, (iii) ER2 earphones + Bose Series II Aviation Headset with active noise-reduction off, and (iv) ER2 earphones + Bose Series II Aviation Headset with active noise-reduction on. Overall ambient noise level in the camera was 73 dB SPL and the maximum octave-band SPL was 68 dB SPL at 250 Hz. Threshold elevations in the PET camera were greatest with ER2 (17 dB, 125 Hz) earphones and lowest with ER2 earphones + Bose Series II Aviation Headset (8 dB at 250 Hz) with active noise-reduction. Thus, PET scanner noise had little or no effect on threshold when stimuli were presented through ER2 earphones covered with an activated Bose Series II Aviation Headset. PMID- 11195941 TI - Use of the 400 Hz period evoked potential in the prediction of loudness discomfort levels in normal hearing adults. AB - This study investigated normally-hearing adult subjects to establish whether the 400 Hz Period Evoked Potential (PEP) can be used to predict Loudness Discomfort Level (LDL). Parameter-intensity functions were obtained using the response measures (400 Hz components) of amplitude, phase, magnitude squared coherence (MSC) and phase coherence (PC). The best predictor of the subjective LDL was found to be the gradient of the individual's amplitude-intensity function for significant (MSC > 0.264 and/or PC > 0.525) responses only. In this case 82% are predicted within 10 dB and there is a maximum error of 15 dB. PMID- 11195942 TI - Multifrequency multicomponent tympanometry in normal and otosclerotic ears. AB - A multifrequency multicomponent admittance meter was used to evaluate 70 ears of patients affected by fenestral otosclerosis (Os ears), monolateral (16 cases) or bilateral (27 cases). The 16 contralateral ears of the patients with monolateral otosclerosis who presented a pure-tone air-bone gap less than 10 dB were evaluated separately (Cos ears). A group of 48 ears belonging to 24 otologically normal subjects (N ears), with hearing thresholds better than or equal to 10dB HL in the frequencies between 250 and 8000 Hz served as a control group. The purpose of the study was to evaluate the acoustic admittance characteristics of the three groups of ears, with particular regard to the parameters represented by the resonance frequency (RF), the acoustic conductance value (G) at RF and the individual interaural differences in these two parameters in the N and Cos groups. The degree to which fenestral otosclerosis can influence variations of RF and the correlation between the value of RF and conductive hearing loss in patients with clinically confirmed pictures and in the controlateral ears in the cases where the disease was clinically unilateral were also investigated. The study reveals statistically significant differences between the RF means in the N group (1085 +/- 244Hz) vs the Os group (1264 +/- 320 Hz) (p < 0.001) and between the G means in the N group (5.33 +/- 1.72 mmhos) vs the Os group (4.46 +/- 2.54 mmhos) (p = 0.04) and N group vs Cos group (3.42 +/- 2.27 mmhos) (p < 0.001). No correlation was found between the value of RF and conductive hearing loss. This study also shows how prognostic value may also be attributed to conductance at middle-ear pressure balancement: extremely low values for this parameter at RF are indicative of initial otosclerotic involvement of the oval window. PMID- 11195943 TI - Symptoms, disability and handicap in unilateral peripheral vestibular disorders. Effects of early presentation and initiation of balance exercises. AB - The aim of this study was to obtain a profile of disability and handicap in patients with unilateral peripheral vestibular disorders presenting to a specialist tertiary care unit. Two validated questionnaires were sent to patients who had a unilateral peripheral vestibular disorder as defined by strict criteria. Some patients still suffered moderate handicap and disability 5 years after the initial symptoms related to a unilateral vestibular disorder, although the duration of symptoms (onset to questionnaire completion) did not correlate with severity of disability and handicap, as judged by questionnaire scores. However, patients presenting to the unit within 6 months of onset of vertigo commenced balance exercises significantly earlier and had significantly lower disability scores than patients presenting later. A high proportion of non compliance with, and delay in initiation of, vestibular rehabilitation exercises was noted in the total patient sample, while compliance with, and early initiation of, Cooksey Cawthorne exercises were significantly correlated with low disability and questionnaire scores. These findings suggest that early referral to a specialist balance unit for patients with persistent dizziness is associated with better outcome. PMID- 11195944 TI - Auditory function among young occupational divers: a 3-year follow-up study. AB - Auditory function was measured in a 3-year follow-up study of 54 young occupational divers divided into high-exposure (n = 23) and low-exposure (n = 31) groups. The divers performed open-sea dives with a median number of 132 dives (range 44-766) during follow-up. At the start of follow-up, hearing in the high exposure group was reduced compared with that in the low-exposure group. During the follow-up period, the total group experienced a significantly reduced hearing ability at 4 kHz in the left ear. No difference in change between the last and the first measurement for both ears combined was found when the two groups were compared. A regression analysis of measurements at the end of follow-up shows an association between the loss of hearing in the left ear at 6 and 8 kHz and the total number of years of diving. This indicates that diving may contribute to hearing impairment. PMID- 11195945 TI - Effect of frequency content on categorical loudness normalization. AB - In this study, increases in loudness with increases in bandwidth, termed loudness summation, were derived from loudness growth functions estimated using a loudness scaling procedure. The results revealed that at equal loudness category, categorical loudness summation was generally larger in normal-hearing than in hearing-impaired subjects; furthermore, the increase in loudness summation at intermediate loudness levels observed in the former, was absent in the latter. These results, in broad agreement with recent data from the literature, can be explained in the light of physiological data on cochlear compression. One implication of these results regarding hearing aid fitting was that channel-by channel loudness normalization was effective only when the incoming sound was closed in bandwidth to one of the test stimuli. PMID- 11195946 TI - Interrater agreement on tympanometry in infants. AB - Two-hundred and forty-two tympanograms of infants were interpreted according to a standard operating procedure independently by an audiologist and ten study doctors from the Finnish Otitis Media Vaccine Trial. The interrater agreement among the study doctors according to Kappa index was excellent (kappa = 0.80). The agreement was significantly better on curves taken during pre-scheduled healthy visits than during sick visits due to respiratory infection (p < 0.001). In addition concurrent knowledge of the clinical ear status significantly improved the agreement on abnormal curves (flat B-curves and failed F-curves, p < 0.001). The clinical differences between the groups were minor. The age of the infant had no effect on interpretation. The agreement between the audiologist and the study doctors was also excellent (kappa = 0.77). Excellent agreement can be achieved in infant tympanometry through adequate instruction and training. PMID- 11195947 TI - Severe-profound hearing impairment and health-related quality of life among post lingual deafened Swedish adults. AB - Health-related quality of life (HRQL) was measured with the Nottingham Health Profile (NHP) in 311 Swedish adults suffering from severe-profound hearing impairment (sensorineural hearing loss in the better ear of > or = 70 dB HL at a frequency of 1.0 kHz) for comparisons with a normal-hearing population. The subjects completed NHP and a questionnaire regarding bio-psycho-social status. Generally, subjects with profound hearing loss reported lower HRQL. Significant differences were obtained for lack of energy, emotional reactions and social isolation. Females with profound impaired hearing tended overall to have lower HRQL than the males. The persons with severe-profound hearing impairment working full-time reported higher HRQL than those with a partial or full disablement pension and were comparable with the hearing population. Severe-profound hearing impairment is associated with an impact on HRQL of the sufferers, especially their emotional and social coping and energy resources. The profound hearing impaired persons seem to constitute a risk group for worse psychosocial adjustment and need greater attention and support. PMID- 11195948 TI - Speech perception after multichannel cochlear implantation in Finnish-speaking postlingually deafened adults. AB - This study was done to examine the short-term and long-term effects of multichannel cochlear implantation on speech perception in Finnish-speaking adults. The subjects comprise 20 adults. Pure-tone thresholds (0.125-8kHz), discrimination of phoneme quantity, sentence recognition, word recognition, phoneme recognition and listening performance were studied before and after implantation. After switch-on of the implant, the median pure-tone threshold values in the sound field were comparable to the level of mild hearing impairment. Most improvement in sentence recognition took place during the 6 months after the switch-on (mean score 74%). In word recognition, most improvement took place during the 12 months after the switch-on (mean score 66%), and clear improvement was noted even thereafter. In phoneme recognition, the performance of the subjects improved over the entire follow-up period, and 24 months after the switch-on the mean score was 52%. Individual variation was seen in the performance of the subjects. With 3 months of listening experience, all subjects were able to recognize some speech without speechreading, and they gained good functional benefit from the implant. The use of speech recognition tests with different degrees of difficulty is essential for the follow-up of adult cochlear implant subjects. PMID- 11195949 TI - Sun Protection is Fun! A skin cancer prevention program for preschools. AB - Children and their caregivers are prime candidates for intervention to curb the rising incidence of skin cancer in the United States. Preschools provide a unique opportunity to influence the sun protection practices of parents and teachers on behalf of young children. Sun Protection is Fun!, a comprehensive skin cancer prevention program developed by The University of Texas M. D. Anderson Cancer Center in collaboration with The University of Texas-Houston Health Science Center School of Public Health, was introduced to preschools in the greater Houston area. The program's intervention methods are grounded in Social Cognitive Theory and emphasize symbolic modeling, vicarious learning, enactive mastery experiences, and persuasion. Program components include a curriculum and teacher's guide, videos, newsletters, handbooks, staff development, group meetings designed to encourage schoolwide changes to support the program, and sunscreen. The intervention map, including objectives for program development, implementation, and evaluation, is discussed. PMID- 11195950 TI - Project SOAR: a training program to increase school counselors' knowledge and confidence regarding suicide prevention and intervention. AB - School counselors are often the lead individuals in school suicide prevention programs. All school counselors in Dallas, Texas, receive training through Project SOAR (Suicide, Options, Awareness, and Relief), a suicide prevention program. This study assessed Dallas school counselors' knowledge of suicidal risk factors and perceived ability to initiate appropriate steps when confronted with a suicidal student. A two-page, 44-item survey was distributed to all Dallas school counselors attending a mandatory meeting in spring 1999. A total of 186 school counselors (75%) responded. Most had been a school counselor for less than 10 years and one-half received initial SOAR training less than four years ago. The majority strongly agreed that they could recognize suicidal warning signs, assess a student's risk for suicide, and offer support to a suicidal student. In addition, most knew the intervention steps to take when a student assessed at high suicidal risk. When compared to school counselors nationwide, these counselors reported increased confidence in identifying students at suicidal risk. PMID- 11195951 TI - Analysis of a bi-state, multi-district, school-based hepatitis B immunization program. AB - A descriptive correlational research design assessed factors influencing participation and completion rates, and to determine vaccine administration costs, in a school-based Hepatitis B vaccination program. Of 18,046 students in public and private schools in the metropolitan Kansas City, Mo., area, 12,986 (73.4%) participated with approximately 75% of these students completing the vaccine series. Larger schools reported decreased participation and completion rates. Both rates were highest in schools providing educational interventions. Schools with a large population of commercially insured students reported low participation rates (65%), but high completion rates (85%). Schools with a high number of Medicaid-eligible students had high participation rates (97%), but low completion rates (67%). The vaccine cost $5.06 per dose to administer. PMID- 11195952 TI - A meta-analysis examining effects of school sexuality education programs on adolescents' sexual knowledge, 1960-1997. AB - This study analyzed and synthesized findings from selected studies conducted from 1960 through 1997 regarding effects of school sexuality education on adolescents' sexual knowledge. This purpose was achieved using meta-analysis. Sixty-seven studies that met the selection criteria were included in the meta-analysis. The 67 studies reported 72 outcomes regarding sexual knowledge, which were grouped into six independent variables related to knowledge about sexuality. A weighted effect size method developed by Hedges and Olkin was calculated using all studies. For all studies, 97% of weighted effect sizes were positive. The weighted average effect size on sexual knowledge across all studies of 0.41 was statistically significant, indicating a significant difference occurred between control and experimental groups' mastery of objectives related to sexual knowledge. It was concluded that sexuality education programs positively affect overall sexual knowledge. PMID- 11195953 TI - Who wants to be healthy? PMID- 11195954 TI - Implications of growing up digital. PMID- 11195955 TI - [Effect of blood concentrations of preovulatory estradiol on the quality of eggs and pre-embryos in patients treated with fertilization in vitro]. AB - The objective was to investigate if the preovulatory estradiol concentrations obtained during controlled ovarian hyperstimulation (COH) have effect on reproductive outcome. The study included a total of 198 in vitro fertilization (IVF) cycles. Patients were divided into four groups according to serum preovulatory estradiol concentrations. In low responder patients was observed significantly decreased oocyte and preembryo quality compared with normal or high responders (P < 0.01). In this work high response do not have effect on IVF outcome. The clinical results indicate that low estradiol levels the day of hCG administration are apparently correlated with poor oocyte and embryo quality. PMID- 11195956 TI - [Comparative study between estradiol valerate combined with cyproterone acetate, and conjugated equine estrogens combined with medroxyprogesterone acetate as hormone replacement therapy in climacteric]. AB - OBJECTIVE: To compare the effectiveness in the control of climacteric symptoms, the tolerability and the uterine bleeding pattern between two types of hormone replacement therapy. MATERIAL AND METHODS: 81 postmenopausal women between 40 and 60 years age with vasomotor symptoms were studied. Randomly it was administered: I. Conjugated equine estrogens (CEE)-Medroxyprogesterone acetate (MPA): 21 tablets with 0.625 mg of CEE and 10 tablets with 5 mg of MPA which were taken with the last ten tablets of CEE in each cycle (n = 3 7). II. E2V-CPA: 11 tablets with 2 mg of E2V and 10 tablets with 2 mg of E2V and 1 mg of CPA (n = 44). Each cycle comprised 28 days. The treatments were compared with squared Chi and Mann Whitney U test. RESULTS: The hot flushes presence was significantly greater in the group with CEE-MPA (p < 0.03). Severe throbs at the end of the study had a trend to be more frequent in the group with EC-MPA (p < 0.06). At the end of the study there was a greater frequency of breast tenderness in the group with CEE MPA (P = 0.009). CONCLUSIONS: Both treatments have good effectiveness, tolerability and same bleeding pattern. Only the frequency of hot flushes, the presence of severe throbs and breast tenderness were lower in the group with E2V CPA, that makes this preparation an option that can have a better acceptance by the women. PMID- 11195957 TI - [Prenatal steroids for fetal maturation in preterm birth. Experience at an institution]. AB - INTRODUCTION: Prenatal steroids have been proved useful in the prevention of respiratory distress syndrome (RDS) and other complications in premature infants. OBJECTIVE: To analyze retrospectively the impact of prenatal steroids in premature infants < 34 weeks. MATERIAL AND METHODS: Two hundred nineteen premature infants were divided into two groups: Group I (n = 145) without prenatal steroids and Group II (n = 74) with steroids. Maternal age, prenatal control, gestational age, gender, weight, Apgar score at 1 and 5 minutes, duration of neonatal hospital care, the presence or absence of RDS, intraventricular haemorrhage (IVH), necrotising enterocolitis (NEC), chronic lung disease (CLD) and neonatal death were analyzed. Chi square test and OD ratios were calculated. RESULTS: Significant statistical difference were found in maternal age, prenatal control, and birth weight. Gestational age, gender and Apgar score at 1 and 5 minutes showed no significant difference. RDS and CLD incidence proved to be lower in group II (with prenatal steroids) showing a significant statistical of X2 = 31.32; p < 0.01 and X2 = 5.42; p < 0.01 respectively. Intraventricular difference (X2 = 5.02; p < 0.1), NEC (X2 = 1.47; p < 0.1), duration of neonatal hospital care and neonatal death showed no significant difference. DISCUSSION: As reported by other authors, RDS incidence in premature infants is reduced by the use of prenatal steroids, and secondarily the incidence of CLD. No effect was found in the presence of IVH even though the OD ratio showed a protective effect. No beneficial effect nor an increase in the frequency of NEC was demonstrated. It is necessary to incorporate strategies at different levels that have the objective of preventing premature births and its complications. PMID- 11195959 TI - [Breast angiosarcoma]. AB - OBJECTIVE: To report the case of a female with Mammary Angiosarcoma. SETTING: Breast Unit of Oncology Service from Hospital General de Mexico. CASE REPORT: A 28 year old female patient was noted to have a left painless breast mass with reddish-violaceous macular lesions in the overlaying skin in upper quadrants, which she had initially discovered 2 years previously. The patient described a progressive breast enlargement. Mammography showed dense tissue without focal mass. A contrast-enhanced Magnetic Resonance of left breast was performed, and 10.5 x 8.5 cm enhancing vascular mass with irregular borders that occupied the entire superior portion of the breast was identified, the mass extended to the pectoral fascia but no evidence of muscle invasion. An incisional Biopsy of the breast mass was performed and the biopsy was interpreted as low grade Mammary Angiosarcoma. Left Simple Mastectomy with partial pectoral resection was performed; and final histopathologic result was intermediate grade Mammary Angiosarcoma. Immunohistochemistry was positive for Factor VIII, Anti Ulex Europeaus and CD 31. CONCLUSION: High index suspect is mandatory for an opportune diagnosis and treatment of Angiosarcoma. Magnetic resonance has a potential role in guiding clinical management. PMID- 11195958 TI - [Comparative assessment of efficacy and safety of assisted vaginal delivery with forceps and with vacuum extractor]. AB - We performed a prospective, controlled, randomized trial to compare de safety and efficacy between the vaginal assisted delivery with vacum extractor forceps. We included a control group of primigravidae. We use the ACOG application criteria for operative obstetrics. We measured the differences in regard to indication for operative delivery, obstetric trauma and the general characteristics of the patients. A total of 210 patients were included which were distributed in three groups. In the first group we included the patients of vacum extractor, the second group of forceps and the third the control group. In our results we found no statistically significant differences among three groups in regard to the general characteristics and obstetric trauma. In the vacum extractor group we found six cefalohematomas (8.5%), two newborns with skin laceration (2.8%) and four newborns with cerebral edema (5.7%). In the forceps group we had two newborns diagnosed with cefalohematomas (2.8%), seven newborns with cerebral edema (10%) and scalp laceration on four newborns (6%). In the control group we found one cefalohematoma (1.4%) and cerebral edema in four newborns (5.7%). We did not find statistically significant differences when we compared the group of the vacum and the forceps. CONCLUSION: With this information we concluded that both instruments are equal in regard to efficacy and safety when they are use by experimented hands and following the application criteria. Nevertheless, there is a high incidence of vaginal injuries and obstetric trauma in the newborn in the operative delivery compared with the control group without an important increase in the perinatal mortality. PMID- 11195960 TI - [Use captopril and estradiol-medroxyprogesterone in premenopausal hypertensive patients]. AB - INTRODUCTION: The premenopause period is that which precedes the actual menopause, when a decrease of the ovarian hormones is present, leading to cardiovascular diseases as arterial hypertension, acute myocardial infarction and cerebrovascular diseases. OBJECTIVE: We evaluated the antihypertensive response of the estradiol-medroxyprogesterone, to reduce arterial pressure in the premenopausal patient. MATERIAL AND METHODS: In a clinical trial from March 1997 to September 1998, 106 patients with systemic hypertension, symptoms hypoestrogenism and estradiol levels less than 30 pg/mL were evaluated. They were randomized at a trial in two groups with pursuit of 6 months. Group A: 53 with captopril, Group B: 53 with estradiol-medroxyprogesterone. The arterial pressure, cholesterol, triglycerides and symptoms hypoestrogenism were analyzed before and after the treatment. The statistical analysis was performed with Student T. RESULTS: A decrease of arterial pressure was observed with estradiol, the same as with captopril with a p < 0.05. Decrease of cholesterol and triglycerides were more significant in the estradiol group with a p < 0.05. A bigger attenuation of symptoms of the hypoestrogenism existed in the estradiol group. CONCLUSIONS: The antihypertensive response with estradiol was the same as with captopril in the premenopausal patient with systemic hypertension. PMID- 11195961 TI - [Maternal risk factors associated with anencephaly]. AB - INTRODUCTION: Anencephaly has factors of risk genetics, environmental and maternal. OBJECTIVE: Identify maternal factors of risk for anencephaly. DESIGN: Case-control study. SETTING: Department of Gyneco-Obstetrics and Pediatrics; second level Social Security Hospital. PARTICIPANTS: 69 pregnant patients attended in their delivery, 23 cases and 46 controls. INTERVENTIONS: We applied a questionnary with questions about factors of risk to each patient with anencephaly children (cases), and to two mothers with healthy children (controls). MEASUREMENTS: The data were analyzed and in boards 2 x 2 resisting differentiates them with x2 test, and the association was measured with odds ratio (OR). Results greater than 1.5 with IC95% by above 1 were significant. RESULTS: Incidence of anencephaly is 2.82/1,000 live births. Association with maternal age, pregnancy, gestational pathology, exposition to high temperatures, mother occupation, exposition to chemical or physical agents, was not found. Protective effects associated, with drug administration during gestation, mainly multivitamin preparations, was found. CONCLUSIONS: The incidence is high, it is a public health problem. During pregnancy probability of anencephaly was less frequent in mothers receiving multivitamin preparations. PMID- 11195962 TI - [Acute fatty liver of pregnancy. Report of a case and review of the literature]. AB - Acute Fatty Liver of Pregnancy. The acute fatty liver of pregnancy (AFLP) is an uncommon entity, potentially fatal, which affects women during the last quarter of pregnancy. It is characterized by a prodromic period of symptoms followed by jaundice, hepatic failure, clotting disorders and fatty infiltration of the liver, evident through hepatic biopsy. The incidence ranks from 1 to 20 thousand births, and it is more frequent among women with multiple pregnancies. We report the case of a 29-year-old patient, with multiple pregnancy 33 to 34 weeks of gestation, blood pressure values of 140/90 mmHg, 160,000/dL platelets, PT 25.6 seconds, TPT 64.7 seconds, blood glucose 52 mL/dL, creatinine 2.1 mg/dL, uric acid 11.9 mg/dL, lactic dihydrogenase 1063 U/l, GPT 220 U/l, AF 1172 U/l, total bilirubin 8.4 mg/dL, proteinuria 30 mg/dL. A cesarean section was practiced after correcting the coagulation disorders. The first twin was a male with birth weight of 2,070 g, APGAR 8-9; the second twin was a female fetal death weighting 2,050 g. Hepatic biopsy confirmed the diagnosis. The cause of AFLP is unknown. The frequency among multiple pregnancies is higher. Almost half of the cases have hypertension and proteinuria. There are also high levels of both transaminases, phosphatase and bilirubins and hypoglycemia. The prothrombin time is enlarged. The differential diagnostic between pre-eclampsia and AFLP is not crucial since the obstetric management is the same. The main treatment is promptly deliverance and general measures. The obstetrician must be aware of this hepatic disease. PMID- 11195963 TI - [Intrahepatic cholestasis of pregnancy, an unpredictable fetal risk: report of a case and review of the literature]. AB - This is a clinical case of intrahepatic cholestasis of pregnancy that developed fetal death few hours after a reactive non-stress test. A 35 year old woman who suffered intrahepatic cholestasis in two previous pregnancies with good outcome. In her last pregnancy she had again intrahepatic cholestasis with abnormal liver tests. The clinical evolution, as well as electronic fetal heart monitoring and ultrasonographic evolution were all normal except for the fetal growth that was restricted, but symmetric. At 35 4/7 weeks of gestation she developed prodromic uterine contractions and a non-stress test was normal. However, 8 hours later the patient returned for reexamination and the fetus was found dead and at birth was a symmetrically small male baby. The fetus' genetic study and placenta's histological study were both normal. The patient cholestasis was resolved few weeks later. PMID- 11195964 TI - Influenza in Canada--1999-2000 season. PMID- 11195965 TI - Two serologically non-groupable Neisseria meningitidis strains from clinical specimens identified by molecular method as serogroup B meningococci. PMID- 11195966 TI - Isolation, purification, and characterization of glutathione S-transferase from oat (Avena sativa) seedlings. AB - Glutathione S-transferase (GST) from oat seedlings was purified by ammonium sulfate precipitation and glutathione (GSH) affinity chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed the presence of two major protein subunits with molecular masses of 29 and 31 kDa, respectively. Isoelectric focusing revealed a major band with pI of 3.43 and a minor band with pI of 7.42. Kinetic analysis with respect to 1-chloro-2,4-dinitrobenzene (CDNB) as substrate revealed a Km of 1.18 mM and Vmax of 0.94 micromol/min and a specific activity of 17.96 micromol/min/mg. Inhibition studies indicated that oat GST is strongly inhibited by chlorophyllin, hemin, and anthocyanin and only weakly by bilirubin and biliverdin. PMID- 11195967 TI - Native fluorescence and mag-indo-1-protein interaction as tools for probing unfolding and refolding sequences of the bovine serum albumin subdomain in the presence of guanidine hydrochloride. AB - Changes in the fluorescence spectrum of tryptophans Trp 134 and Trp 212 in bovine serum albumin (BSA) and of Trp 214 of human serum albumin in the presence of the chaotropic agent guanidine hydrochloride (Gnd) were studied. A detailed analysis of the fluorescence spectrum of native BSA yielded the fluorescence spectrum for each tryptophan of BSA. Modifications in the binding of Mag-indo-1 to BSA, which results in a specific quenching of the fluorescence spectrum of Trp 134 associated with an energy transfer from Trp 134 to the protein-bound Mag-indo-1, were also investigated. Changes occurring when the Gnd concentration is decreased stepwise cover a larger concentration scale of Gnd than the reverse protocol, allowing one to suggest that the resulting conformational changes in the subdomain IA of BSA involve at least three different steps. PMID- 11195968 TI - Construction of a ferritin reactor: an efficient means for trapping various heavy metal ions in flowing seawater. AB - An apparatus consisting of two pumps, a mixer, a ferritin reactor, and a spectrophotometer was constructed to study the ability to trap various heavy metal ions (M2+) and the dynamics of a reconstituted ferritin reactor in flowing seawater. Reconstituted pig spleen ferritin (PSFr) is assembled from apo-protein shell to form a reconstituted iron core. The main components of the PSFr are its core, which contains an Fe2+:Pi stoichiometry of 6.0 +/- 0.5, reconstituted from pig spleen apoferritin (apo PSF), Fe2+, inorganic phosphate (Pi), and O2 (0.6 atm). The Fe3+-Pi clusters within the PSFr core exhibit resistance to salt ranging from 1% to 6% NaCl. The ferritin reactor consists of PSFr and an oscillating bag. Using the reactor, M2+ ions such as Cd2+, Zn2+, Co2+, and Mn2+ are directly trapped by the ferritin. We found a 1:2 +/- 0.2 stoichiometry of the trapped M2+ to the released iron as measured by chemical analysis or atomic absorption spectrometry; nontransient elements such as Na+, K+, Ca2+, etc., were scarcely trapped by the reactor. This study provides basic conditions for establishing a ferritin reactor and a convenient means for monitoring the pollution of heavy metal ions in seawater. PMID- 11195969 TI - Chaperone-mediated refolding of recombinant prochymosin. AB - It has been verified that prochymosin is characterized by a two-stage refolding: dilution of unfolded protein into pH 11 buffer followed by neutralization at pH 8; the high-pH step is indispensable. Here we demonstrate that one-stage refolding around pH 8 can be achieved when GroE or 10-fold molar excess (rather than catalytic concentration) of protein disulfide isomerase (PDI) over prochymosin is present. The helping effect varies with the oxidation states of prochymosin. GroE and PDI increase the reactivation of the unfolded, partially reduced and the unfolded, oxidized prochymosin from 5% to 40% and from 50% to 100%, respectively. For the unfolded and fully reduced prochymosin, GroE does not have a positive effect, whereas PDI promotes renaturation from 2% to 28%. Based on our previous and present observations, we propose that at pH 8 there may be two kinds of incorrect interactions within and between prochymosin polypeptides leading to unproductive pathways: one prevents disulfide rearrangement, which can be avoided by high pH; the other interferes with acquisition of native conformation, which can be relieved by GroE and PDI. PMID- 11195970 TI - Amino acid sequences of hemoglobin from guinea fowl (Numida meleagri) and California quail (Lophortyx californica) with phylogenetic analysis of major groups of Galliformes. AB - We determined the complete amino acid sequences of the hemoglobin of two species, guinea fowl and California quail, in Galliformes from intact globin chain and chemical cleavage fragments in order to analyze the molecular evolution of hemoglobin for the classification of Galliformes. Galliformes have two types of hemoglobin components, HbA and HbD, which consist of identical beta chain and different alpha chains. The sequences are similar to globin chains of Galliformes reported previously. These sequences were compared with those of other Galliformes (Phasianidae, Meleagrididae) using duck and goshawk as out-groups. The phylogenetic tree of major groups of Galliformes based on hemoglobin was similar to the tree model produced based on the amino acid sequence of lysozyme c. PMID- 11195971 TI - Effects of Ca2+ on the activity and stability of methanol dehydrogenase. AB - The effects of exogenously added Ca2+ on the enzymatic activity and structural stability of methanol dehydrogenase were studied for various Ca2+ concentrations. Methanol dehydrogenase activity increased significantly with increasing concentration of Ca2+, approaching saturation at 200 mM Ca2+. The effect of Ca2+ on the activation of MDH was time dependent and Ca2+ specific and was due to binding of the metal ions to the enzyme. Addition of increasing concentration of Ca2+ caused a decrease of the intrinsic tryptophan fluorescence intensity in a concentration-dependent manner to a minimum at 200 mM, but with no change in the fluorescence emission maximum wavelength or the CD spectra. The results revealed that the activation of methanol dehydrogenase by Ca2+ occurred concurrently with the conformational change. In addition, exogenously bound Ca2+ destabilized MDH. The potential biological significance of these results is discussed. PMID- 11195972 TI - Light chain of botulinum A neurotoxin expressed as an inclusion body from a synthetic gene is catalytically and functionally active. AB - Botulinum neurotoxins, the most potent of all toxins, induce lethal neuromuscular paralysis by inhibiting exocytosis at the neuromuscular junction. The light chains (LC) of these dichain neurotoxins are a new class of zinc-endopeptidases that specifically cleave the synaptosomal proteins, SNAP-25, VAMP, or syntaxin at discrete sites. To facilitate the structural and functional characterization of these unique endopeptidases, we constructed a synthetic gene for the LC of the botulinum neurotoxin serotype A (BoNT/A), overexpressed it in Escherichia coli, and purified the gene product from inclusion bodies. Our procedure can provide 1.1 g of the LC from 1 L of culture. The LC product was stable in solution at 4 degrees C for at least 6 months. This rBoNT/A LC was proteolytically active, specifically cleaving the Glu-Arg bond in a 17-residue synthetic peptide of SNAP 25, the reported cleavage site of BoNT/A. Its calculated catalytic efficiency kcat/Km was higher than that reported for the native BoNT/A dichain. Treating the rBoNT/A LC with mercuric compounds completely abolished its activity, most probably by modifying the cysteine-164 residue located in the vicinity of the active site. About 70% activity of the LC was restored by adding Zn2+ to a Zn2+ free, apo-LC preparation. The LC was nontoxic to mice and failed to elicit neutralizing epitope(s) when the animals were vaccinated with this protein. In addition, injecting rBoNT/A LC into sea urchin eggs inhibited exocytosis dependent plasma membrane resealing. For the first time, results of our study make available a large amount of the biologically active toxin fragment in a soluble and stable form. PMID- 11195973 TI - Steady-state kinetic analysis of human ubiquitin-activating enzyme (E1) using a fluorescently labeled ubiquitin substrate. AB - We report the synthesis of fluorescently labeled ubiquitin (Ub) and its use for following ubiquitin transfer to various proteins. Using Oregon green (Og) succinimidyl ester, we prepared a population of Ub mainly labeled by a single Og molecule; greater than 95% of the Og label is associated with Lys 6 of Ub. We demonstrate that Og-Ub is efficiently accepted by Ub-utilizing enzymes, such as the human ubiquitin-activating enzyme (E1). We used this fluorescent substrate to follow the steady-state kinetics of human E1-catalyzed Ub-transfer to the ubiquitin-carrier enzyme Ubc4. In this reaction, E1 uses three substrates: ATP, Ubc4, and Ub. The steady-state kinetics of Og-Ub utilization by E1 is presented. We have also used analytical ultracentrifugation methods to establish that E1 is monomeric under our assay condition (low salt) as well as under physiological condition (150 mM NaCl). PMID- 11195974 TI - Kinetic characterization of the double mutant R148A/E182S of glycogen phosphorylase kinase catalytic subunit: the role of the activation loop. AB - Many protein kinases are activated by phosphorylation in a highly conserved region of their catalytic subunit, termed activation loop. Phosphorylase kinase is constitutively active without the requirement for phosphorylation of residues in the activation loop. The residue which plays an analogous role to the phosphorylatable residues in other protein kinases is Glu182, which makes contacts to a highly conserved Arg148. In turn, Arg148 adjacent to the catalytic Asp149, enabling information to be transmitted from the activation loop to the catalytic machinery. The double mutant R148A/E182S has been kinetically characterized. The mutation resulted in an approximate 16- to 22-fold decrease in the kcat/Km value of the enzyme. The kinetic data, discussed in the light of the structural data from previously determined complexes of the enzyme, lead to the suggestion that the activation loop has a major role in substrate binding but also in correct orientation of the groups participating in catalysis. PMID- 11195975 TI - Effects of denaturing and stabilizing agents on the inhibitory activity and conformational stability of Schizolobium parahyba chymotrypsin inhibitor. AB - The conformational stability of the Schizolobium parahyba chymotrypsin inhibitor (SPCI) was investigated based on conformational changes and inhibitory activity in the presence of chaotropic and stabilizing agents. At 90 degrees C, the half lifetime of SPCI was 154 min, while in the presence of 1 M KCl and 20% PEG 20,000, it was drastically reduced to 6 and 3 min, respectively. In contrast, at 90 degrees C, the SPCI structure remained unaltered with the addition of 1 mM DTT and 56% glycerol. The reduction of the two disulfide bonds caused conformational changes in the SPCI without altering the inhibitory activity, suggesting that disulfide bonds are irrelevant to the maintenance of SPCI conformation. Unfolded structures were formed in the presence of 6 M GdnHCl, while in the presence of 8 M urea, destabilization was due to peptide bond rupture. These results suggest that the thermal inactivation of SPCI involves conformational changes and that hydrophobic and electrostatic interactions play a significant role, while the disulfide bonds are of secondary importance in maintaining the high thermal stability of SPCI. PMID- 11195977 TI - Binding study of riboflavin-binding protein with riboflavin and its analogues by differential scanning calorimetry. AB - Thermal unfolding parameters of hens' egg-white riboflavin-binding-protein (RBP) were measured by differential scanning calorimetry. Thermal denaturation scans of apoRBP and RBP complexes with riboflavin and its analogues (FMN, N10 DL-glyceryl isoalloxazine, and N10 omega-hydroxypentyl isoalloxazine) have been measured. It was found that ligand binding causes increase of RBP thermal stability, as manifested by a change of denaturation temperature from 60.8 degrees C for apoRBP to 72.8 degrees C for RBP-Rf complex. For RBP-FMN complex, the denaturation temperature of 73.0 degrees C was even higher than for the RBP-Rf complex. The other two flavin analogues showed transition temperatures in between 66.9 degrees C and 68.8 degrees C, respectively. Analysis of excess heat capacity data showed that the best fit was the sum of two independent thermal transitions. One of the transitions, which contributed approximately 70% to the total heat effect, has transition temperature in the broad range of 60.5-73.2 degrees C; the other transition temperature is in the narrower range of 65.4-71.1 degrees C. The observed transitions can be related to RBP domains. PMID- 11195976 TI - Purification and characterization of a trypsin-like enzyme with fibrinolytic activity present in the abdomen of horn fly, Haematobia irritans irritans (Diptera: Muscidae). AB - This work describes the purification and characterization of a trypsin-like enzyme with fibrinolytic activity present in the abdomen of Haematobia irritans irritans (Diptera: Muscidae). The enzyme was purified using a one-step process, consisting of affinity chromatography on SBTI-Sepharose. The purified protease showed one major active proteinase band on reverse zymography with 0.15% gelatin, corresponding to a molecular mass of 25.5 kDa, with maximum activity at pH 9.0. The purified trypsin-like enzyme preferentially hydrolyzed synthetic substrates with arginine residue at the P1 position. The Km values determined for three different substrates were 1.88 x 10(-4), 1.28 x 10(-4), and 1.40 x 10(-4) M for H alpha-benzoyl-Ile-Glu-Gly-Arg-p-nitroanilide (S2222), DL-Ile-Pro-Arg-p nitroanilide (S2288), and DL-Phe-Pip-Arg-p-nitroanilide (S2238), respectively. The enzyme was strongly inhibited by typical serine proteinase inhibitors such as SB PMID- 11195978 TI - Conformational studies of a melittin-inhibitor complex. AB - The conformation of a melittin-inhibitor complex was studied by solution NMR, solid-state NMR, and circular dichroism. In solution, binding was studied by titrating inhibitor against melittin in dimethyl sulfoxide, methanol, aqueous buffer, and dodecylphosphocholine micelles. The change in chemical shift of Trp19 resonances and the formation of a precipitate at 1:1 molar ratio indicated that the inhibitor was bound to melittin. Solid-state NMR also showed a change in chemical shift of two labeled carbons of melittin near Pro14 and a change in 1HT1 relaxation times when complexed with inhibitor. Rotational resonance experiments of melittin labeled in the proline region indicated a change in conformation for melittin complexed with inhibitor. This observation was also supported by circular dichroism measurements, indicating a reduction in alpha-helical structure for increasing ratios of inhibitor bound to melittin. PMID- 11195979 TI - Temperature, pH, and solvent isotope effects on cytochrome c peroxidase mutant N82A studied by proton NMR. AB - The mutant of baker's yeast cytochrome c peroxidase-CN with Ala82 in place of Asn82, [N82A]CcPCN, exhibits a complex solution behavior featuring dynamic interconversion among three enzyme forms that so far have only been detected by NMR spectroscopy. Proton NMR studies of [N82A]CcPCN reveal resonances from each of the three enzyme forms and show that the interconversion among forms is controlled by the pH, temperature, and isotope composition (H2O vs. D2O) of the buffer solution. No evidence for a key hydrogen bond between His52 and heme coordinated cyanide is found in any of the enzyme forms, indicating that disruption of the extensive distal hydrogen bonding network is the source of this phenomenon. PMID- 11195980 TI - The interaction between impulsivity and neighborhood context on offending: the effects of impulsivity are stronger in poorer neighborhoods. AB - This research blends 2 traditions of theorizing on the causes of crime, one focused on the role of individual differences and the other focused on structural and contextual variables. Two related studies examined the relations among impulsivity, neighborhood context, and juvenile offending. The first, cross sectional study uses a large sample of 13-year-old inner-city boys, whereas the second, longitudinal study offers a conceptual replication using 17-year-old inner-city boys who are a subset of the original sample. Across both studies, results indicate that the effects of impulsivity on juvenile offending are stronger in poorer neighborhoods. Furthermore, nonimpulsive boys in poor neighborhoods were at no greater risk for delinquency than nonimpulsive boys in better-off neighborhoods. PMID- 11195981 TI - Perceptual organization in schizophrenia: the processing of symmetrical configurations. AB - The hypothesis that the perceptual organization dysfunction of patients with poor premorbid schizophrenia is due to a deficit in global visual sensory store processing was tested by assessing their ability to process symmetrical configurations that develop early and have strong prepotent structures. Two same different judgment tasks in which performance varies as a function of the symmetrical organization and task demands were administered to participants with good and poor premorbid schizophrenia, those with mood disorders, and normal controls. Like the other groups, poor premorbid schizophrenics' latency and error response patterns closely paralled the a priori model of adequate processing. The results support their competence in perceptually processing symmetrical configurations and disconfirm the hypothesis that their input deficiencies represent a general deficiency in all forms of perceptual organization. The implications for specifying their early input dysfunction are discussed. PMID- 11195982 TI - Vulnerability to depression: cognitive reactivity and parental bonding in high risk individuals. AB - Although various conceptual proposals have suggested that disruptions in childhood bonding processes may be linked to the origins of these cognitive structures, little research has tested these proposals. This study assessed the information processing of vulnerable individuals and its relationship to childhood bonding. Formerly depressed (vulnerable) and never depressed (nonvulnerable) individuals participated in a mood induction task followed by an attentional allocation task. Results indicated that vulnerable individuals uniquely diverted attention toward negative stimuli when they were in a negative mood. Furthermore, level of maternal caring was found to be associated with performance on this task for vulnerable individuals in this mood state. These data support the idea that cognitive variables form a pathway between troublesome parental-child/adolescent interactions and depression. PMID- 11195983 TI - Phobia-relevant illusory correlations: the role of phobic responsivity. AB - The authors investigated the role of phobic responsivity in the generation of phobia-relevant illusory correlations. As a means of disentangling the contributions of prior fear and elicited fear responses, half of a group of phobic women received 1 mg alprazolam (n = 21), and half received a placebo (n = 22). A group of nonfearful women (n = 24) was included to control for prior fear per se. Participants were exposed to slides of spiders, weapons, and flowers that were randomly paired with a shock, a siren, or nothing. Postexperimental covariation estimates and on-line outcome expectancies were assessed. Irrespective of both prior and elicited fear, participants postexperimentally overassociated spiders and shock. Yet, only women with spider phobia displayed a persisting fear-confirming expectancy bias. This bias was similar for the placebo and alprazolam groups. Thus, the bias appeared to be due to preexisting phobogenic beliefs, whereas phobic responsivity played a negligible role. PMID- 11195984 TI - Induced emotional interpretation bias and anxiety. AB - Five experiments are reported showing that the interpretation of personally relevant emotional information can be modified by systematic exposure to congruent exemplars. Participants were induced to interpret ambiguous information in a relatively threatening or a benign way. Comparison with a baseline condition suggested that negative and positive induction had similar but opposing effects. Induction of an interpretative bias did not require active generation of personally relevant meanings, but such active processing was necessary before state anxiety changed in parallel with the induced interpretative bias. These findings provide evidence consistent with a causal link between the deployment of interpretative bias and anxiety and reveal something of the processes underlying this association. PMID- 11195985 TI - Psychological and physiological predictors of response to carbon dioxide challenge in individuals with panic disorder. AB - Past studies in nonclinical samples have found that suffocation fear, but not a behavioral index of carbon dioxide (CO2) sensitivity (i.e., breath-holding duration), predicts anxious response to CO2 challenge. These associations were examined in individuals with panic disorder while adding more sensitive indices of CO2 sensitivity. Consistent with the earlier studies, the authors found that suffocation fear predicted anxious responding to CO2 challenge but breath-holding duration did not. However, highly precise measures of CO2 sensitivity, not included in earlier studies, did predict anxious challenge responding. These findings support the predictive value and possible etiological relevance of both specific psychological variables and physiological CO2 sensitivity in panic vulnerability. Further work is still needed to determine whether the findings are specific to panic disorder. PMID- 11195986 TI - Posttraumatic stress disorder and retrospectively reported stressor exposure: a longitudinal prediction model. AB - There has been recent concern about the degree to which posttraumatic stress disorder (PTSD) symptomatology influences reports of prior exposure to highly stressful life events. In this longitudinal study of 2,942 male and female Gulf War veterans, the authors documented change in stressor reporting across 2 occasions and the association between change and PTSD symptom severity. A regression-based cross-lagged analysis was used to examine the relationship between PTSD symptom severity and later reported stressor exposure. Shifts in reporting over time were modestly associated with PTSD symptom severity. The cross-lagged analysis revealed a marginal association between Time 1 PTSD symptom severity and Time 2 reported stressor exposure for men and suggested that later reports of stressor exposure are primarily accounted for by earlier reports and less so by earlier PTSD symptomatology. PMID- 11195987 TI - Evidence for a genetic etiology of early-onset delinquency. AB - Age at onset of antisocial behavior discriminates persistent and transitory offenders. The authors proposed that early-onset delinquency has an underlying genetic influence that manifests in problems related to inhibition, whereas late onset delinquency is more environmentally mediated. To test these notions, they selected 36 early starters, 86 late starters, and 25 nondelinquent controls from a large sample of 11-year-old twins and compared them on several measures related to inhibition and a peer group measure. As expected, early starters had more psychological, behavioral, and emotional problems related to inhibition than late starters and controls. A longitudinal analysis indicated an increase an antisocial behavior among peers of late starters shortly before their delinquency onset. Family history data and a twin analysis provided evidence of greater genetic influence on early-onset than late-onset delinquency. PMID- 11195988 TI - Psychosocial predictors of the short-term course and outcome of major depression: a longitudinal study of a nonclinical sample with recent-onset episodes. AB - Three variables have been hypothesized to play important roles in prolonging the course of depressive episodes: a ruminative response style, significant interpersonal relationships, and childhood adversity. The authors examined whether these variables predicted the short-term course of major depressive disorder (MDD). Participants (n = 84) were college students with a recent-onset major depressive episode. Assessments included several interview and self-report measures, and data on interpersonal relationships were obtained from close confidants. Follow-up interviews were conducted 6 months later. After controlling for baseline severity, harsh discipline in childhood significantly predicted mean level of depression across the follow-up and level of depression at follow-up. Harsh discipline was also significantly associated with relapse but not with recovery. After controlling for baseline severity, rumination and the interpersonal variables did not predict the outcome of MDD. PMID- 11195989 TI - Are the discrepancies between self- and others' appraisals of competence predictive or reflective of depressive symptoms in children and adolescents: a longitudinal study, Part II. AB - Two cohorts of children and adolescents (who started 6th grade in 1993 and 1996), parents, teachers, and peers participated in a 4-wave, 2-year, longitudinal study of perceived competence and depressive symptoms. The authors assessed children's tendencies to underestimate their competence (discrepant self-appraisals) relative to the appraisals of significant others. We also assessed the degree to which self-appraisals reflected the evaluations of others (reflective self appraisals). Domains of competence were academic competence, physical appearance, behavioral conduct, social acceptance, and athletic competence. Cross-sectional analyses indicated that depressive symptoms correlated with reflective and discrepant self-appraisals. Longitudinal analyses revealed that reflective and discrepant self-appraisals predicted subsequent depressive symptoms and that depressive symptoms predicted discrepant but not reflective self-appraisals. Clinical implications of the findings are discussed. PMID- 11195990 TI - Memory illusions: false recall and recognition in adults with Asperger's syndrome. AB - As persons on the autistic spectrum are known not to use semantic features of word lists to aid recall, they might show diminished susceptibility to illusory memories that typically occur with lists of associated items. Alternatively, since such individuals also have poor source monitoring, they might show greater susceptibility. The authors found that adults with Asperger's syndrome (n = 10) recalled similar proportions of a nonpresented strong associate of the study list items, compared with controls (n = 15). In Experiment 2, rates of true and false recognition of study list associates did not differ significantly between Asperger (n = 10) and control (n = 10) participants. Moreover, the Asperger participants made fewer remember and more know judgments than controls for veridical but not for false recognitions. Thus, deficits found in some aspects of memory in people with Asperger's syndrome do not affect their susceptibility to memory illusions. PMID- 11195991 TI - Realism of confidence in obsessive-compulsive checkers. AB - The study examined whether obsessive-compulsive (OC) checkers have reduced confidence in their knowledge. OC checkers were compared with panic disorder (PD) patients and nonpatient controls using a calibration-of-knowledge procedure. Participants completed a general knowledge questionnaire, rated their confidence in each answer, and estimated the total number of correct answers. These responses were converted to 2 measures of confidence relative to performance- over/underconfidence and over/underestimation. OC checkers had lower scores than nonpatients did on both measures, whereas the PD patients did not differ from either group. For the OC checkers, relative confidence was inversely related to the severity of obsessions. The authors speculate that confidence may depend on a confirmation bias in testing hypotheses and that the reduced confidence in OC checkers may reflect a disconfirmation bias in this population. PMID- 11195992 TI - Prospective analysis of comorbidity: tobacco and alcohol use disorders. AB - Alcohol use disorders (AUD) and tobacco use disorders (TD) frequently co-occur. The authors examined AUD-TD comorbidity over time using a state-trait (ST) model. The ST model represents variance in AUD/TD as a traitlike factor that spans measurement occasion and identifies distinct sources of variance in AUD-TD comorbidity. The ST model was evaluated on 450 young adults (baseline age = 18.5 years; 51% with family history of alcoholism) assessed 5 times over 7 years. The ST model demonstrated superior fit over a first-order autoregressive model. The tendency to diagnose with AUD and TD was partially explained by family history of alcoholism; this relationship was mediated by childhood stressors, alcohol expectancies, and behavioral undercontrol. Results supported a common third variable influence (vs. directional) model of comorbidity. The ST model is an important conceptual and methodological approach to the prospective study of comorbidity in general. PMID- 11195993 TI - Biases in eye movements to threatening facial expressions in generalized anxiety disorder and depressive disorder. AB - The study investigated biases in selective attention to emotional face stimuli in generalized anxiety disorder (GAD) and depressive disorder, using a modified probe detection task. There were 4 face types: threatening, sad, happy, and neutral. Measures of attentional bias included (a) the direction and latency of the initial eye movement in response to the faces and (b) manual reaction time (RT) to probes replacing the face stimuli 1,000 ms after their onset. Results showed that individuals with GAD (without depressive disorder) were more likely to look first toward threat faces rather than neutral faces compared with normal controls and those with depressive disorder. They also shifted their gaze more quickly toward threat faces, rather than away from them, relative to the other two groups. There were no significant findings from the manual RT data. Implications of the results for recent theories of clinical anxiety and depression are discussed. PMID- 11195994 TI - Impaired positive inferential bias in social phobia. AB - People with social phobia report anticipatory and retrospective judgments about social situations that appear consistent with a negative interpretative bias. However, it is not at all clear that biased interpretative inferences are made "on-line;" that is, at the time that ambiguous information is first encountered. In a previous study, volunteers who were anxious about interviews were found to lack the positive on-line inferential bias that was characteristic of nonanxious controls but also failed to show a bias favoring threatening inferences (C. R. Hirsch & A. Mathews, 1997). This finding was confirmed in the present study, in which social phobic patients showed no evidence of making on-line emotional inferences, in contrast with socially nonanxious controls who were again clearly biased in favor of positive inferences. The authors concluded that nonanxious individuals are characterized by a benign on-line inferential bias, but that this is impaired in people with social phobia. PMID- 11195995 TI - Implicit memory bias for threat-relevant information in individuals with generalized social phobia. AB - The authors used a noise judgment task to investigate implicit memory bias for threat in individuals with generalized social phobia (GSP). Participants first heard neutral sentences (e.g., "The manual tells you how to set up the tent.") and social-threat sentences (e.g., "The classmate asks you to go for drinks."). Implicit memory for these sentences was then tested by asking participants to rate the volume of noise accompanying the presentation of these "old" sentences intermixed with "new" sentences that had not been previously presented. Implicit memory for old sentences is revealed when participants rate the noise accompanying old sentences as less loud than the noise accompanying new sentences. Those with GSP demonstrated an implicit memory bias for social-threat sentences, whereas controls did not. This differential priming effect suggests that information about threat may be automatically accessed in GSP. PMID- 11195997 TI - Aberrant semantic and affective processing in people at risk for psychosis. AB - Semantic and affective processing were examined in people at risk for psychosis. The participants were 3 groups of college students: 41 people with elevated Perceptual Aberration and Magical Ideation (PerMag) scores, 18 people with elevated Social Anhedonia (SocAnh) scores, and 100 control participants. Participants completed a single-word, continuous presentation pronunciation task that included semantically related words, affectively valenced words, and semantically unrelated and affectively neutral words. PerMag participants exhibited increased semantic priming and increased sensitivity to affectively valenced primes. SocAnh participants had increased sensitivity to affectively valenced targets. PMID- 11195996 TI - Increases in manic symptoms after life events involving goal attainment. AB - Bipolar disorder has been conceptualized as an outcome of dysregulation in the behavioral activation system (BAS), a brain system that regulates goal-directed activity. On the basis of the BAS model, the authors hypothesized that life events involving goal attainment would promote manic symptoms in bipolar individuals. The authors followed 43 bipolar I individuals monthly with standardized symptom severity assessments (the Modified Hamilton Rating Scale for Depression and the Bech-Rafaelsen Mania Rating Scale). Life events were assessed using the Goal Attainment and Positivity scales of the Life Events and Difficulties Schedule. As hypothesized, manic symptoms increased in the 2 months following goal-attainment events, but depressed symptoms were not changed following goal-attainment events. These results are congruent with a series of recent polarity-specific findings. PMID- 11195998 TI - Borderline personality: traits and disorder. AB - Although the 5-factor model (FFM) has been advocated as an alternative to representing the construct of borderline personality, some argue that this diagnosis carries essential information that is not well captured by the FFM. The present study examined antecedent, concurrent, and predictive markers of construct validity in a sample of 362 patients with personality disorders. The results indicated that neuroticism best distinguished borderline and nonborderline patients, whereas the FFM as a whole captured a sizable proportion of the variance in the borderline diagnosis. However, the residual of the borderline diagnosis that was not explained by the FFM was found to be significantly related to childhood abuse history, family history of mood and substance use disorders, concurrent symptoms, and 2-year and 4-year outcomes. Thus, some elements of the borderline diagnosis may not be fully captured in a 5 factor representation. PMID- 11196000 TI - The paradox of normal neuropsychological function in schizophrenia. AB - Mounting evidence suggests that compromised neurocognitive function is a core feature of schizophrenia. However, some studies have found neuropsychologically normal schizophrenia patients. To address this apparent contradiction, we blindly rated individual neuropsychological profiles of 75 schizophrenia patients and 91 control participants on the basis of methods developed by L. J. Seidman, S. V. Faraone, W. S. Kremen, J. R. Pepple, M. J. Lyons, and M. T. Tsuang (1993). Almost one-quarter of the patients were classified as neuropsychologically within normal limits (WNL). Despite significantly worse neuropsychological performance, WNL patients had higher estimated premorbid ability than did controls. Compared to a subset of controls matched on overall neuropsychological function, WNL patients had higher estimated premorbid ability and current IQs. Our results favor the view that even neuropsychologically normal schizophrenia patients have compromised cognitive function relative to their presumed expected or premorbid level of intellectual ability. PMID- 11195999 TI - Naltrexone's effects on reactivity to alcohol cues among alcoholic men. AB - The mechanisms of naltrexone's effects on urges to drink during abstinence are unclear. Naltrexone may suppress either urges to drink specifically or appetitive responses in general. The effects of naltrexone on cue reactivity to alcoholic and sweet nonalcoholic beverages were investigated. Alcohol-dependent men (N = 53) in treatment received naltrexone (50 mg) or placebo. Four hours later, they received baseline assessment, exposure to fruit juice, and exposure to their usual alcoholic beverage in 3-min trials. Naltrexone reduced urge to drink and self-reported attention to the alcohol cues, not at the initial exposure but after repeated exposures to alcohol cues. Naltrexone reduced negative affect across baseline and alcohol trials. No effects of naltrexone on responses to the nonalcoholic appetitive beverage cues were found, suggesting that general appetite suppression does not mediate the effects of naltrexone on urges. PMID- 11196001 TI - Self-perceived competence and the relation between life events and depressive symptoms in adolescence: mediator or moderator? AB - In a 2-wave longitudinal study, 9th-grade students (N = 468) completed self report measures of stressful life events, depressive symptoms, and 5 domains of self-perceived competence (i.e., academic competence, social acceptance, physical appearance, behavioral conduct, and athletic competence). Teachers and peers also reported about the participants' depressive symptoms. In longitudinal analyses, negative (but not positive) events related to depressive symptoms. Results suggested that self-perceived competence served as a mediator (but not a moderator) of this relation. Negative events predicted changes in self-perceived competence. Self-perceived competence predicted changes in depressive symptoms. Also, the direct effect of negative events on depressive symptoms diminished after controlling for self-perceived competence. PMID- 11196002 TI - Contextual insensitivity in schizophrenic language processing: evidence from lexical ambiguity. AB - The authors investigated whether contextual failures in schizophrenia are due to deficits in the detection of context or the inhibition of contextually irrelevant information. Eighteen schizophrenia patients and 24 nonpsychiatric controls were tested via a cross-modal semantic priming task. Participants heard sentences containing homonyms and made lexical decisions about visual targets related to the homonyms' dominant or subordinate meanings. When sentences moderately biased subordinate meanings (e.g., the animal enclosure meaning of pen), schizophrenia patients showed priming of dominant targets (e.g., paper) and subordinate targets (e.g., pig). In contrast, controls showed priming only of subordinate targets. When contexts strongly biased subordinate meanings, both groups showed priming only of subordinate targets. The results suggest that inhibitory deficits rather than context detection deficits underlie contextual failures in schizophrenia. PMID- 11196003 TI - Dysfunctional thinking in major depressive disorder: a deficit in metacognitive monitoring? AB - Speed of response to attitudinal statements has predictive behavioral significance and reflects the relative contributions of "automatic" access to precomputed schematic representations and slower "controlled" on-line processing. Latencies to Dysfunctional Attitude Scale (A. N. Weissman & A. T. Beck, 1978) and neutral statements were measured in 30 depressed patients and 30 nondepressed controls. For controls, responses incompatible with functional schemas were markedly slowed. This pattern of latencies is consistent with the operation of metacognitive monitoring of potential dysfunctional responses, dependent on limited controlled processing resources. For patients, there was no evidence of selective slowing for these or any other form of response. Results suggest that depressed patients have a deficit of metacognitive monitoring of dysfunctional cognitive products. PMID- 11196004 TI - Stressful life events, bipolar disorder, and the "kindling model". AB - A common misconception is that bipolar disorder is an endogenous process. However, previous research suggests a role for life events in the onset of and recovery from bipolar episodes. Yet, there remains some question as to whether the relationship between life events and onset changes over the course of the disorder as a result of the number of episodes an individual has experienced. Using a rigorous interview measure of stressful life events, the current study tested the kindling model (R. M. Post, 1992), which theorizes that major life events play a diminishing role over the course of illness in bipolar patients. Analyses revealed that the number of episodes experienced does not appear to have a significant effect on bipolar 1 patients' reactivity to external stressors. In addition, the results suggest that a more complex relationship exists among age, stress, and onset of new episodes than can be adequately explained by the kindling model. PMID- 11196005 TI - A comparison of two life stress assessment approaches: prospective prediction of treatment outcome in recurrent depression. AB - Research on life stress has been characterized by inconsistent results, which some researchers attribute to different assessment methodologies. Generally, studies have used either self-report checklists or investigator-based interviews. To test whether different results are derived from these approaches, the authors compared information from a self-report measure of life stress with the additional data available from a follow-up investigator-based measure in prospectively predicting the outcome of treatment for recurrent major depression. The 2 approaches produced different results, with investigator-based life events predicting lower probability of remission and self-report life events either predicting increased likelihood of remission or not predicting at all. The results demonstrated that methodology may account for some of the inconsistencies in the life stress literature. PMID- 11196006 TI - Expressed emotion and attributions in the relatives of bipolar patients: an analysis of problem-solving interactions. AB - Among the relatives of schizophrenic and depressed patients, high expressed emotion (EE) attitudes are associated with "controllability attributions" about the causes of patients' symptoms and problem behaviors. However, previous studies have judged EE attitudes and causal attributions from the same assessment measure, the Camberwell Family Interview (CFI; C. E. Vaughn & J. P. Leff, 1976). The authors examined causal attributions among relatives of 47 bipolar patients, as spontaneously expressed to patients in family problem-solving interactions during a postillness period. Relatives rated high EE during the patients' acute episode (based on the CFI) were more likely than relatives rated low EE to spontaneously attribute patients' symptoms and negative behaviors to personal and controllable factors during the postillness interactional assessment. Thus, the EE-attribution linkage extends to the relatives of bipolar patients evaluated during a family interaction task. PMID- 11196007 TI - Electroencephalographic asymmetries in adolescents with major depression: influence of comorbidity with anxiety disorders. AB - This study examined whether adolescents with major depressive disorder (MDD) display the abnormal electroencephalographic (EEG) alpha asymmetries found in depressed adults. Resting EEG was recorded in 25 right-handed female outpatients (19 with MDD, 11 of whom also had a current anxiety disorder; 6 with anxiety disorders only) and 10 non-ill controls. In contrast to the non-ill controls, adolescents having MDD but no anxiety disorder showed alpha asymmetry indicative of less activation over right than over left posterior sites. Within the MDD patient group, comorbid anxiety disorders reduced the posterior alpha asymmetry, supporting the potential importance of evaluating anxiety in studies of regional brain activation in adolescent MDD. These preliminary findings are similar to those from adult studies that suggest that MDD is associated with right parietotemporal hypoactivation. PMID- 11196008 TI - Psychiatric disorders and dissatisfaction with social relationships: does type of relationship matter? AB - The specificity of the association between 9 Axis I psychiatric disorders and quality of the relationship with spouse, relatives, and friends was evaluated for married participants who completed the Ontario Health Survey Mental Health Supplement (N = 4,933). When the authors controlled for the quality of other social relationships, not getting along with one's spouse was related to 6 disorders, with the strongest associations found for generalized anxiety disorder, major depression, panic, and alcohol problems; 4 associations remained significant when they controlled for comorbid disorders. Not getting along with relatives and friends was generally unrelated to psychiatric disorders when they controlled for the other social relationships. Results indicate that the association between marital quality and psychiatric disorders is not an artifact of general social dissatisfaction and that this association is significant for several disorders. PMID- 11196009 TI - Child development after maternal tocolysis with beta-sympathomimetic drugs. AB - The psycho-social development of both preterm and term children whose mothers reported tocolytic treatment was assessed at the ages of 2, 4.5, and 8 years. Term children exposed to tocolysis showed a higher rate of psychiatric disorders as well as poorer cognitive and motor performance than controls. In the preterm children no adverse impact of tocolysis could be found. The results are discussed concerning possible ways in which tocolytic treatment may influence child development. Restrictions because of the preliminary character of this study and the need of further prospective studies to clarify the developmental impact of tocolysis are also considered. PMID- 11196010 TI - Risk factors in childhood that lead to the development of conduct disorder and antisocial personality disorder. AB - With juvenile crime on the rise, understanding and preventing juvenile delinquency is one of the greatest challenges facing mental health professionals today. Recognizing early signs of conduct disorder (CD) can be difficult, but identifying risk factors is an important step in preventing a child's progression to CD or Antisocial Personality Disorder (APD). This paper focuses on various risk factors for CD and APD, such as intrinsic individual differences, psychosocial/environmental factors, genetic and neurochemical factors. Early recognition and intervention may prevent the progression from aggressive and maladaptive behaviors to CD and later APD. PMID- 11196011 TI - Trauma and personality correlates in long-term pediatric cancer survivors. AB - To explore the relationship between PTSD and trauma-spectrum symptoms, including personality and functional correlates, in long term pediatric cancer survivors (N = 40), we assessed these constructs with a structured interview for PTSD, a clinical interview, and self-report questionnaires. Thirty-five out of 40 participants (88%) currently met at least one trauma symptom at a functionally significant level. These survivors demonstrate high levels of restraint and low levels of distress, representative of a repressive adaptive style. After more than 5 years since treatment completion, the relatively high levels of current trauma-spectrum symptoms may reflect the long-term deleterious impact of childhood cancer. PMID- 11196012 TI - Implications of aggressive children's positively biased relatedness views for future relationships. AB - The present study examined the tendency of aggressive children to generalize the positive bias in their perceptions of relatedness across different interpersonal relationships. Secondly, it examined the implications of distorted perceptions of relatedness for quality of aggressive children's future relationships. Subjects included 62 second and third grade children nominated and rated by teachers as aggressive. Self- and others' appraisals of relationship quality were gathered across four interpersonal domains (i.e., mother, teacher, mentor, and peer). Children's positively biased perceptions of social relatedness were concordant across adult relationship domains but not across the peer domain, suggesting that children's relationships with adults and peers represent somewhat distinct socialization contexts. As expected, children who inflate levels of social relatedness establish less close relationships with novel partners (mentors). The findings emphasize the need for clinicians to focus on mental representations while planning interventions with aggressive children. PMID- 11196013 TI - Spatial orientation adjustments in children with autism in Hong Kong. AB - Abnormal spatial orientation and body postures in children with autism often interfere with visual abilities to attend tasks and social interactions. Twenty four children diagnosed with autism from Kowloon, Hong Kong were assessed for spatial orientation and spatial management abilities. Positive changes in spatial orientation were evident when the children wore ambient prism lenses and included changes in posture from slanted to erect. Adjustments in spatial management were evident in improved ball catching ability, a task requiring visual tracking and eye-hand coordination. The findings suggest that alterations to the sensory systems may lead to behavioral change in some children. PMID- 11196014 TI - Associated health risks of adolescents with disordered eating: how different are they from their peers? Results from a high school survey. AB - In this study, we compare health risks of adolescents with disordered eating to those of their peers without disordered eating. A self-report health survey from a community sample of 1769 high school students was used to compare emotional, medical, and social behaviors of these two groups. Risk data for disordered eating students was compared within and across genders. Adolescents with disordered eating are at increased risk for emotional and physical health problems compared to their peers. Overall health risks for boys and girls with disordered eating are quite similar. However, boys with disordered eating develop associated health risk profiles that differentiate them from male peers by having increased mental health, sexual and physical abuse, and general health problems. Girls with disordered eating have associated health risks for substance use and sexual risk-taking that distinguished them from their female peers. PMID- 11196015 TI - N232S, G741R and D778G beta-cardiac myosin mutants, implicated in familial hypertrophic cardiomyopathy, do not disrupt myofibrillar organisation in cultured myotubes. PMID- 11196016 TI - Give a dog a bad name--the story of DDT. PMID- 11196017 TI - 1999 HIV surveillance result--little grounds for pessimism. PMID- 11196018 TI - Registry: unusual HIV transmission in children under the age of 10 years. PMID- 11196019 TI - Russian and Cape health partners. PMID- 11196020 TI - Discrimination beyond the grave. PMID- 11196021 TI - Commitment more than skin deep. PMID- 11196022 TI - Mabasa leads a new struggle. PMID- 11196023 TI - Prevention of vertical transmission of human immunodeficiency type 1 virus in a managed care setting. PMID- 11196024 TI - Re-use of single-use disposable instrumentation. PMID- 11196025 TI - The Jaipur paradigm--a conceptual framework for understanding social susceptibility and vulnerability to HIV. PMID- 11196026 TI - Another unfortunate interpretation of section 7(2) of the Employment Equity Act. PMID- 11196027 TI - Emerging glycopeptide resistance in gram-positive organisms. PMID- 11196028 TI - The role of clinical assessment in the prevention of osteoporotic fractures. PMID- 11196029 TI - Chronic glucocorticoid therapy and osteoporosis--an under-recognised problem in South Africa. PMID- 11196030 TI - Vancomycin-resistant Staphylococcus aureus occurs in South Africa. PMID- 11196031 TI - A case of vancomycin-resistant enterococcal endocarditis. PMID- 11196032 TI - Ewart's sign in tuberculous pericarditis. PMID- 11196033 TI - Prevalence of nasopharyngeal antibiotic-resistant pneumococcal carriage in children attending private paediatric practices in Johannesburg. AB - OBJECTIVES: To determine the nasopharyngeal carriage rate, serogroups/types, and antibiotic resistance of Streptococcus pneumoniae in children attending paediatric practices in the private sector in Johannesburg and to relate patterns of resistance to antimicrobial exposure and other demographic characteristics in individual children. DESIGN: A total of 303 children aged from 1 month to 5 years were recruited from eight private paediatric practices in northern Johannesburg. Nasopharyngeal samples were taken and parent interviews were conducted. RESULTS: Pneumococci were isolated from 121 children (40%). The most common serotypes were 6B, 19F, 6A, 23F, 14, and 19A. Carriage was significantly associated with prior hospital admission (odds ratio 1.89) and day care attendance (odds ratio 2.31) and was negatively associated with antibiotic use within the previous 30 days. Antibiotic resistance was found in 84 isolates (69.4%); 45 (37.2%) were multiply resistant. One-third of the pneumococci showed intermediate level resistance to penicillin and 12.4% were highly resistant. There was a high level erythromycin resistance in 38% of the isolates. A total of 94/214 children (42%) had recently used antibiotics and were four times more likely to carry antibiotic-resistant pneumococci (P < 0.05). CONCLUSION: Pneumococcal resistance was significant in this group of children with easy access to paediatric services and antibiotic use. The implication of such high resistance for the treatment of pneumococcal diseases is that high-dose amoxicillin is the preferred empirical oral therapy for treatment of otitis media. Ceftriaxone or cefotaxime should be used in combination with vancomycin for the treatment of meningitis until a cephalosporin resistant pneumococcal cause is excluded. Intravenous penicillin or ampicillin will successfully treat pneumococcal pneumonia in this population. Antimicrobial resistance among pneumococci colonising children in the private sector has increased dramatically in recent years. PMID- 11196034 TI - Perimenopausal wrist fracture--an opportunity for prevention and management of osteoporosis. AB - OBJECTIVE: Review of Medscheme's administrative databases to study the relationship between hip fracture and previous wrist fracture in peri- and postmenopausal women. DESIGN: Retrospective analysis of 1995-1998 data for women aged 50 and above hospitalised for management of wrist fracture. Those identified were subjected to further review to establish rates of osteoporosis and/or hip fracture. Osteoporosis and/or hip fracture rates were also determined for a control population. MAIN OUTCOME MEASURES: Osteoporosis investigation and management rates in controls v. subjects who had experienced a previous wrist fracture. RESULTS: A total of 701 subjects was admitted to hospital for management of a wrist fracture between 1995 and 1998; and compared with 1,385 similarly aged controls. Diagnosis of osteoporosis and admission for hip fracture were more common in women who had experienced a previous wrist fracture (relative risk (RR) 1.55; 95% confidence interval (CI) 1.19-2.03 for osteoporosis, and RR 3.32; 95% CI 1.16-9.69 for hip fracture). Of 10 hip fractures which occurred in the wrist fracture group, 9 were in women not diagnosed as having, or treated for, osteoporosis. CONCLUSION: While women with a history of wrist fracture are more likely than controls to be tested and treated for osteoporosis, it nevertheless appears that insufficient attention is being paid to this premonitory event. PMID- 11196035 TI - Monitoring and management of bone status in patients on chronic glucocorticoid treatment--the Medscheme experience. AB - OBJECTIVE: Review of administrative databases to gain insight into the investigation, management and sequelae of bone disease in patients on long-term glucocorticoid treatment. DESIGN: Retrospective analysis of 1998 pharmaceutical and clinical claims data for +/- 2 million lives administered by Medscheme. Data were extracted for members registered with the chronic medication programme as eligible for chronic glucocorticoid treatment. Those identified were subjected to further review for evidence of osteoporosis and/or hip fracture. Subgroup analysis of peri- and postmenopausal women was carried out and compared against a control group. MAIN OUTCOME MEASURES: Osteoporosis investigation and treatment rates in males and females; frequency of hip fractures; prescribing profiles; role of underlying disease, glucocorticoid route, gender and age in development of osteoporosis. RESULTS: A total of 1,614 subjects (54% females) was registered for chronic glucocorticoid treatment. Osteoporosis was diagnosed in 14.1% of females and 5.9% of males across a broad age range. Hip fractures were recorded for one female and three males. The subgroup analysis showed that osteoporosis was +/- 1.5 times more common in women receiving glucocorticoids than in peri- and postmenopausal controls, and that there was greater use of vitamin D and calcium supplementation and bisphosphonates in those exposed to glucocorticoids. Multivariate analysis showed overall that female gender, increasing age and oral glucocorticoids were significantly related to osteoporosis. CONCLUSION: Reference to UK and US data suggests that while local practitioners are aware of the effect of glucocorticoids on bone, the level of awareness is probably suboptimal, especially with regard to male patients. PMID- 11196036 TI - Empiric treatment based on Helicobacter pylori serology cannot substitute for early endoscopy in the management of dyspeptic rural black Africans. AB - BACKGROUND: Evidence that chronic gastric Helicobacter pylori (HP) infection is an aetiological factor in dyspepsia, peptic ulcer disease, gastric carcinoma and lymphoma has led to the suggestion that all serologically positive dyspeptic patients should be treated empirically with antibiotics to eradicate the infection, without endoscopic diagnosis. The following study was performed to determine whether such a policy would prove to be of benefit in rural Africa, where endoscopic facilities are lacking and infection rates high. METHODS: Four district clinics were visited and 97 consecutive patients with persistent upper gastro-intestinal symptoms studied. After history-taking and physical examination, a blood sample was taken for HP serology (IgG anti-HP EIA) and endoscopy was performed. RESULTS: In comparison with similar studies in westernised countries HP was considerably more common (80%), and similar to that reported for the background population (83-86%), but peptic ulceration (17%) and gastric cancer (1%) were not. HP status and antibody levels failed to predict the presence of serious disease; patients with 'alarm' signs (78%), cancer (78%) and peptic ulcers (81%) had similar seropositivity rates to patients with non-ulcer dyspepsia (81%). Interestingly, many patients with distal oesophagitis were seronegative (40%). Haemoglobin concentrations and nutritional status were similar in HP-positive and negative patients. On the basis of published decision analysis strategies, empiric treatment of HP-positive patients with uncomplicated dyspepsia could be expected to produce symptomatic relief in 50% of cases, but would have delayed the diagnosis of 3 cases of cancer if patients over the age of 45 were included. CONCLUSION: The lack of association between HP serology and upper gastro-intestinal disease indicates that serological investigation cannot substitute for endoscopy in the management of black Africans with dyspepsia, and that empiric anti-HP therapy cannot be justified. PMID- 11196037 TI - Nutritional status of patients in a long-stay hospital for people with mental handicap. AB - OBJECTIVE: To investigate the general nutritional status of patients in Alexandra Hospital, Cape Town, and to determine whether dietary copper deficiency was causing anaemia in hospital patients. DESIGN: Descriptive and cross-sectional analytical studies. SETTING: A long-stay hospital for people with mental handicap. SUBJECTS: Information was obtained from the total hospital population. In addition, groups of 15 patients were selected from each of two specific wards, one with active and the other inactive patients. To determine whether copper deficiency was causing anaemia, a sample of 30 patients, divided into three groups (a hypochromic microcytic, a normochromic anaemic and a non-anaemic group) was studied. MAIN OUTCOME MEASURES: Body mass indices (BMI) and daily dietary intakes were compared with Recommended Daily Allowance (RDA) values. Serum copper and serum caeruloplasmin levels were used to detect possible copper deficiency. RESULTS: A considerable number of patients were found to be underweight (32% of males and 26% of females had BMIs < 20). A smaller number were obese (6% of males and 17% of females had BMIs > 30). Poor nutrition was more common in severely handicapped patients and those with acquired causes of their mental handicap. Subjects with Down syndrome were generally well nourished and occasionally obese. Poor dietary intakes of biotin, pantothenic acid, vitamin D and copper were encountered. The serum copper and caeruloplasmin values were found to be within normal limits. Patients with hypochromic, microcytic anaemia had higher serum copper and caeruloplasmin levels than those with normochromic anaemia and the control group. CONCLUSIONS: A number of nutritional problems among the inpatient population were found. Many were undernourished, while a smaller number of patients were overweight. In both the active and inactive wards macronutrient intakes were generally within normal limits. However, some micronutrient nutritional deficiencies were encountered. We were unable to establish that dietary copper deficiency was the cause of anaemia in our patients. Elevated serum copper and caeruloplasmin levels found in hypochromic, microcytic patients were thought to result from the existence of low-grade infection, associated with elevation of the acute-phase protein, caeruloplasmin. PMID- 11196038 TI - Critically ill obstetric and gynaecological patients in the intensive care unit. AB - OBJECTIVES: To document mortality among critically ill obstetric and gynaecological patients requiring intensive care unit (ICU) admission and to investigate whether any poor prognostic features could allow for earlier and more aggressive intervention. STUDY DESIGN: A retrospective study of all obstetric and gynaecological patients admitted to the ICU of Johannesburg Hospital between 1985 and 1996. Sixty-one patients were analysed both as a group and as two subgroups- those with incomplete abortions and those with other pregnancy-related diagnoses. RESULTS: Derangements in platelet counts, serum creatinine levels and prothrombin international normalised ratio (INR) were present in all patients on the day of admission to hospital. In the group with incomplete abortions absolute levels of these parameters may be used to identify those patients with a worse outcome. The mortality rate was 38%. CONCLUSION: Early ICU admission and aggressive surgical intervention are strongly recommended in patients with septic incomplete abortions presenting with more than a single organ dysfunction. PMID- 11196039 TI - Motorcycle taxi drivers and sexually transmitted infections in a Peruvian Amazon City. AB - BACKGROUND: In Iquitos, Peru, motorcycle taxis are a common form of public transportation used both by residents and visitors. GOAL: To evaluate the prevalence of factors associated with sexually transmitted disease risk and of Neisseria gonorrhoeae and Chlamydia trachomatis infections among motorcycle taxi drivers working in Iquitos, Peru. STUDY DESIGN: A convenience sample of motorcycle taxi drivers was recruited through street outreach. Participants were confidentially interviewed and provided urine specimens for gonococcal and chlamydial infection testing. RESULTS: A history of sexually transmitted disease (62%) or symptoms in the past year (35%) and of referral of clients to commercial sex workers (60%) was common. The prevalence of gonococcal or chlamydial infection was 3.5%. CONCLUSIONS: Motorcycle taxi drivers are a major means of public transportation in Iquitos, Peru, have high personal risks for sexually transmitted disease, and interface often with at-risk persons. PMID- 11196040 TI - Patterns of chlamydia and gonorrhea infection in sexual networks in Manitoba, Canada. AB - BACKGROUND: The use of sexual network analysis has the potential to further our understanding of sexually tranmitted disease (STD) epidemics and contribute to the development of more effective targeted control strategies. GOAL: To use sexual network analysis to study transmission patterns of chlamydia and gonorrhea in Manitoba, Canada. STUDY DESIGN: Routinely collected case/contact information gathered by public health nurses was used to construct the sexual network. RESULTS: Components within the sexual network ranged in size from 2 to 82 people. Two types of components, designated radial and linear, were described. Large linear components resembled the theoretical structure of STD core groups. Geographic analysis of the largest components demonstrated the potential for STD transmission between isolated rural communities and within different areas of an urban center. CONCLUSIONS: The application of sexual network analysis on a provincial basis demonstrated the importance of a centralized, coordinated approach to STD control. The analysis highlights the need for a greater understanding of the causative factors promoting the formation of different component types, the homogeneity and heterogeneity of behaviors within and between components, and the temporal stability of these patterns. PMID- 11196041 TI - Networks and pathogens. PMID- 11196042 TI - An unusual transmission of Neisseria meningitidis: neonatal conjunctivitis acquired at delivery from the mother's endocervical infection. AB - BACKGROUND: Primary meningococcal conjunctivitis is assumed to be due to the direct inoculation of Neisseria meningitidis into the conjunctival sac from an exogenous source. According to a literature review, no case of neonatal conjunctivitis infection acquired at delivery from maternal endocervicitis has been published. GOAL: To report a case of meningococcal neonatal conjunctivitis acquired at delivery because of the mother's endocervical infection and cross transmission of the strain with her partner. STUDY DESIGN: Strains were characterized by bacteriologic and serologic methods including grouping (agglutination), typing, and subtyping (enzyme-linked immunoabsorbent assay). Molecular analysis was done by pulsed-field gel electrophoresis. RESULTS: The three strains (newborn infant, mother, partner) were of the same antigenic formula (C:NT:P1.NT) and exhibited similar NheI and SpeI pulsed-field gel electrophoresis patterns. CONCLUSION: The identical phenotypic and genomic analysis of strains is the evidence for N meningitidis transmission at delivery from a maternal endocervical infection to the newborn infant and cross transmission between sexual partners. PMID- 11196043 TI - Unsuspected gonorrhea and chlamydia in patients of an urban adult emergency department: a critical population for STD control intervention. AB - BACKGROUND: Urban emergency departments (EDs) providing services to patients at high risk for sexually transmitted infection may be logical sites for intervention. GOAL: To determine the prevalence of gonorrhea (GC) and chlamydia (CT) in an adult ED patient population, and to assess risk factors for infection. STUDY DESIGN: Cross-sectional study of patients aged 18 to 44 in an urban ED, seeking care of any medical nature. Main outcome was positive for GC or CT by urine ligase chain reaction assay. RESULTS: Test results for GC and/or CT were positive in 13.6% of 434 18 to 31 year-olds and in 1.8% of 221 32 to 44 year olds. Of 63 infected individuals identified by the study, 15 (23.8%) were treated at the ED visit. Age < or =31 detected 88% of infections. Among 18- to 31-year old patients, predictive risk factors by multivariate analysis included age <25, >1 sex partner in the past 90 days, and a history of sexually transmitted disease. CONCLUSION: This study identified a high prevalence of GC and CT in patients seeking ED services. Many of these infections were clinically unsuspected. These data demonstrate that the ED is a high-risk setting and may be an appropriate site for routine GC and CT screening in 18- to 31-year-old patients. PMID- 11196044 TI - Incidence and prevalence of chlamydia, herpes, and viral hepatitis in a homeless adolescent population. AB - BACKGROUND: High rates of unprotected intercourse and illegal drug use have been reported among homeless adolescents. As a transient population with the potential to act as disease vectors from one location to another, incidence and prevalence of sexually transmitted infections in this population are of particular concern. GOAL: To assess a homeless adolescent population for incidence and prevalence of Chlamydia trachomatis, herpes simplex virus type 2, hepatitis B virus, hepatitis C virus, HIV, and psychosocial correlates of the acquisition of sexually transmitted infections. STUDY DESIGN: Longitudinal with assessments at baseline, 3 months, and 6 months (n = 536; 319 males and 217 females). RESULTS: Baseline prevalence of C trachomatis was 4.17% for males and 6.30% for females. Prevalence of herpes simplex virus type 2 was 5.73% for males and 12.50% for females. Hepatitis B virus and hepatitis C virus prevalences were 3.60% and 5.0%, respectively. HIV seroprevalence was 0.3%. The incidence of sexually transmitted infections was significantly higher among females than among males (16.7% versus 9.8%) and was associated with inconsistent condom use and, for females, number of partners and sex with older partners. Incident hepatitis B virus and hepatitis C virus infection rates were 3.44% and 6.61%, respectively; both were associated with injection drug use. CONCLUSIONS: Among females, the incidence of herpes simplex virus type 2 (> 25%) and C trachomatis (12%) was relatively high. Inconsistent condom use was the primary factor associated with a significantly greater risk of incident sexually transmitted infections. This was especially true for females with multiple partners. Homeless adolescents also are at high risk for hepatitis B virus and hepatitis C virus infection, primarily associated with self-reported injection drug use. PMID- 11196045 TI - Are emergency departments the next frontier for sexually transmitted disease screening? PMID- 11196046 TI - Implementation of a screening program for chlamydial infection in incarcerated adolescents. AB - BACKGROUND: In collaboration with the Houston Department of Health and Human Services, the authors implemented and evaluated a urine-based chlamydia screening program in incarcerated youth in Harris County, Texas, and assessed predictor variables for infection. GOAL: To implement and evaluate chlamydia screening in incarcerated youth. STUDY DESIGN: The authors determined prevalence of chlamydial infection, treatment rates, and predictor variables in 589 youth and repeated the measures 6 months later in 975 additional youth. RESULTS: Initially, the prevalence of infection was 9.6% in males and 28.1% in females; 88% of infected youth were treated while incarcerated. White males had a significantly lower prevalence of chlamydial infection; however, consistent condom use was not associated with a lower prevalence of chlamydia. In the 6-month assessment of chlamydia prevalence in 975 youth, prevalence and treatment rates remained high and predictor variables were similar. CONCLUSION: The authors instituted a screening program for chlamydial infection in incarcerated youth that was performing well at reassessment 6 months later. PMID- 11196047 TI - Herpes simplex virus type 2 seroepidemiology in Spain: prevalence and seroconversion rate among sexually transmitted disease clinic attendees. AB - BACKGROUND: Only limited data on the seroprevalence of herpes simplex virus type 2 (HSV-2) are available from European countries. Until recently, serologic tests for HSV-2 serotyping have been hampered by cross-reactivity to type-common antigens. The present study aims at providing data on the prevalence of HSV-2 infection in a group of STD clinic attendees using a reliable type-specific immunoassay. GOAL: To evaluate the seroprevalence of HSV-2 and the accumulated incidence of clinical genital herpes infection in a sample of Spanish sexually transmitted disease (STD) clinic attendees. STUDY DESIGN: The study consisted of two parts. First, a cross-sectional study of HSV-2 seroprevalence was conducted in patients with STDs. Second, a prospective cohort study was undertaken to evaluate the accumulated incidence of infection by HSV-2 and of clinical episodes of genital herpes in HSV-2-negative patients included in the first study during a follow-up period of 6 to 18 months. RESULTS: Of the 374 patients (129 men, 245 women) studied, 25% were seropositive for HSV-2 (12% of men, 30% of women). Antibodies to HSV-2 were related to female gender (odds ratio, 2.7; P < 0.001) and to the number of sexual partners (odds ratio, 4.1; P < 0.001). Fifty-two percent of patients (145 of 281 patients) who were initially seronegative returned to the clinic for a second serologic testing, of whom 1% (2 of 145 patients) had seroconverted. None of the patients developed genital herpes during the follow-up period. CONCLUSION: The relatively high seroprevalence (25%) and the low rate (4%) of HSV-2 previously reported in the general population in Spain suggest that the virus circulation may be restricted to certain risk groups. Therefore, future healthcare measures may target specific groups, such as patients with STDs. PMID- 11196048 TI - Slow diffusion of home HIV-specimen collection: provider concerns at odds with client preferences. AB - BACKGROUND: Home specimen collection and telephone counseling (HSCTC) may be a convenient new method for detection of HIV infection among cohorts at high-risk for HIV. GOAL: To evaluate attitudes about HSCTC among participants, HIV counselors, and community advisory board members associated with a national multisite study of persons at high risk for HIV. STUDY DESIGN: Twelve focus groups and surveys were conducted at six sites among 126 counselors, community advisory board members, and cohort participants. RESULTS: Staff and community advisory board members raised concerns about the acceptability, feasibility, safety, and effectiveness of HSCTC. In contrast, participants (92%) reported a willingness to collect blood and oral samples on a frequent basis, and preferred telephone (73%) to office-based counseling. CONCLUSION: Home specimen collection and telephone counseling appear to be preferred by study participants at high risk of HIV infection. Staff and community advisory board members had stronger reservations than prospective users. PMID- 11196049 TI - Curable sexually transmitted infections among the clientele of a family planning clinic in Istanbul, Turkey. AB - BACKGROUND: Integrating screening and treatment of sexually transmitted infections into existing family planning programs can be a good way to fight this problem. Also, the number of studies on the prevalence of certain sexually transmitted infections in this population in Turkey is limited. GOAL: To find out the prevalence of the most common sexually transmitted infections among the clients of an urban family planning clinic and to evaluate demographic characteristics and clinical signs related to sexually transmitted infections. STUDY DESIGN: Samples for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis were collected from 569 women who attended the clinic from December 15, 1997 to March 31, 1998. RESULTS: No case of N gonorrhoeae was found among the samples. The prevalence of C trachomatis infection was 1.9%, whereas the prevalence of of T vaginalis was 2.6%. None of the demographic characteristics or clinical signs was related to these infections. CONCLUSION: Larger studies using more sensitive laboratory tests are needed to determine the prevalence of chlamydial infections in family planning clinics in Turkey. PMID- 11196050 TI - [Evaluation of cognitive disorders and screening of delirium in cancer patients receiving morphine. Comparison of the use of the Elementary Test of Concentration, Orientation and Memory (TELECOM)and of the Mini-Mental State Examination (MMSE)]. AB - OBJECTIVE: The Mini Mental State Examination (MMSE) is the gold standard cognitive test for screening delirium in cancer patients on opioids. But the MMSE is long and requires writing, reading and drawing from patients with various degrees of physical inability. Age and educational level affect the MMSE score. The Blessed Orientation-Memory-Concentration (BOMC) test is strictly oral and brief. This six item test is not affected by age or educational level. PATIENTS AND METHODS: We conducted a validation study of BOMC for screening delirium in cancer patients taking opioids. One physician examined 25 advanced cancer patients 34 times with MMSE and BOMC. Diagnosis of delirium was made by the same examiner according to the DSM IV criteria. The MMSE score was used for diagnosis of cognitive failure. RESULTS: Seventy-six percent of the patients completed the MMSE and 100% the BOMC. Scores of the two tests were correlated (0.71). An average 4 min 12 sec was gained with BOMC compared with MMSE. For a 10/11 cutoff, the BOMC had 83% sensitivity and 95% specificity for delirium diagnosis. Positive and negative predictive values were 91%. The time for the BOMC was correlated with BOMC score (0.6). A BOMC time of 3 min 20 sec had 91% sensitivity and specificity for delirium diagnosis. CONCLUSION: BOMC is more applicable than MMSE for screening delirium in cancer patients. The relationship between BOMC time and delirium deserves further investigations. PMID- 11196051 TI - [Facial diplegias during pregnancy]. AB - BACKGROUND: Facial diplegia is a rare event, most commonly of unknown origin. We report the case of a woman who presented bilateral Bell's palsy a few days after a normal delivery. CASE REPORT: Five days after the delivery of gemellary pregnancy, a 34-year old woman developed complete bilateral facial palsy. No treatment was initially prescribed. She was first seen in our department two weeks after the onset of her illness. The diagnostic work-up was negative and we considered that our patient had bilateral Bell's palsy. Treatment with methylprednisolone and intravenous acyclovir, initiated since admission, have had very limited effect. DISCUSSION: As has already been shown for facial palsy, idiopathic facial diplegia, although exceptional, seems to be more frequent during the last trimester of pregnancy and in the early puerperium. Seven cases have been reported in the literature over the last 30 years. We discuss here the pathophysiology. PMID- 11196053 TI - [A new sign of chronic stomach volvulus in an elderly patient: an anterior gait desequilibrium]. PMID- 11196052 TI - [Reversible pulmonary hypertension in Basedow's disease]. AB - BACKGROUND: An association between pulmonary hypertension and hyperthyroidism has been described. An autoimmune mechanism is usually advocated but a direct effect thyroid hormones on the pulmonary vascular system is also suggested. CASE REPORT: A 49-year-old woman with a history of Graves' disease was admitted for sudden dyspnea. There was no evidence of ischemic stroke and the electrocardiogram and cardiac enzymes were normal. The lung scintiscan did not show any sign of pulmonary embolism. The chest computed tomography was normal. Doppler echocardiography found pulmonary hypertension with systolic pulmonary artery pressure of 68.7 mmHg. Thyroid function tests showed hyperthyroidism with recurrent Graves' disease. Pulmonary hypertension markedly decreased after the euthyroid state was achieved with antithyroid therapy. DISCUSSION: This patient had pulmonary hypertension associated with hyperthyroidism due to Graves' disease. The rapid reversibility of pulmonary hypertension in this case after the achievement of the euthyroid state suggest a pathogenic link between these two disorders and a possible direct effect of thyroid hormones on the pulmonary vascular system. PMID- 11196054 TI - [Gastrointestinal and thyroid localizations of a MALT lymphoma]. PMID- 11196055 TI - [Broncho-pulmonary colonization by Enteromonas hominis in gastroesophageal reflux]. PMID- 11196056 TI - [Dietary fiber or calcium supplementation does not prevent the recurrence of colonic adenomas]. PMID- 11196057 TI - [Concerning the creation of neurovascular units]. PMID- 11196058 TI - [Cannabis arteriopathy]. PMID- 11196059 TI - [An innocent speed selector]. PMID- 11196060 TI - [A virus called HTLV-1. Virological and molecular aspects]. AB - A VIRAL PATHOGEN: HTLV-1, the first oncogenic retrovirus discovered in man carries, in addition to the genes coding for its structural protein, genes for capside and matrix (gag), reverse transcriptase and integrase (pol), protease and envelope (env), a unique region (termed pX) of about 2 kb situated at the position 3' of the env gene that encodes for Tax and Rex regulator proteins. TAX AND REX: These two proteins play a role in the viral cycle. Rex acts at the post transcriptional level; Its capacity to modulate Tax expression could allow the virus to establish a chronic infection with little expression. Tax stimulates viral transcription and also plays a fundamental role in leukecernogenesis by modifying the expression of several genes crucial for cell survival and proliferation. GENETIC STABILITY: The HTLV-1 genome sequence appears to be very stable. Specifically leukernogeneic or neurotrophic strains are unlikely to exist. However, despite this genetic stability, there are molecular variants related to the geographical origin of the virus. PMID- 11196061 TI - [A virus called HTLV-1. Epidemiological aspects]. AB - GEOGRAPHIC DISTRIBUTION AND TRANSMISSION: HTLV-1 is not an ubiquitous virus. 15 to 25 million subjects are estimated to be infected. Endemic areas are recognized in southern Japan, tropical Africa, the Caribbean, some areas in Central and South America, and in few regions of the Middle East and Melanesia. In these endemic zones, 0.5 to 50% of the population, depending on age and gender, have specific antibodies against HTLV-1 antigens. Interhuman transmission can occur from mother to child by prolonged breast feeding, from men to women by sexual intercourse, and from blood exposure via infected lymphoid cells. MOLECULAR EPIDEMIOLOGY: Molecular epidemiology studies have evidenced several molecular types or genotypes of HTLV-1 linked to the geographical origin of the infected population rather than to the associated pathology (leukemia versus neuromyelopathy). The high stability of the HTLV-1 genome is probably related to clonal expansion of infected cells conjugated to the minimal use of the reverse transcriptase. This low variability has been used as a molecular tool to better understand the origin, the evolution and the dissemination of this retrovirus. The current distribution of HTLV-1, and its simian homologue STLV-1, results from at least 4 events: transmission of STLV-1 between different monkey species, transmission of STLV-1 to humans, persistence of HTLV-1 in isolated human populations, and finally global and more recent distribution of HTLV-1 (mainly the cosmopolite subtype) subsequent to migration of virus-infected populations. PMID- 11196062 TI - [Recommendations for the creation of neurovascular units. French Neurovascular Society]. PMID- 11196063 TI - Eye movements and lexical access in spoken-language comprehension: evaluating a linking hypothesis between fixations and linguistic processing. AB - A growing number of researchers in the sentence processing community are using eye movements to address issues in spoken language comprehension. Experiments using this paradigm have shown that visually presented referential information, including properties of referents relevant to specific actions, influences even the earliest moments of syntactic processing. Methodological concerns about task specific strategies and the linking hypothesis between eye movements and linguistic processing are identified and discussed. These concerns are addressed in a review of recent studies of spoken word recognition which introduce and evaluate a detailed linking hypothesis between eye movements and lexical access. The results provide evidence about the time course of lexical activation that resolves some important theoretical issues in spoken-word recognition. They also demonstrate that fixations are sensitive to properties of the normal language processing system that cannot be attributed to task-specific strategies. PMID- 11196064 TI - Priming in sentence processing: intralexical spreading activation, schemas, and situation models. AB - A series of eye-tracking experiments investigated priming in natural language understanding. Intralexical spreading activation accounts of priming predict that the response to a target word will be speeded (i.e., primed) when strong associates appear prior to the target. Schema-based priming accounts predict that priming will occur when the target word is a component of an activated schema or script. Situation model accounts predict that priming will occur when a target word can be integrated easily into an evolving discourse representation. In separate experiments, we measured the effect of associated words, synonyms, and identity primes on processing times for subsequently encountered target words. Our designs crossed prime type (e.g., synonyms vs. unassociated words) with semantic plausibility (i.e., the target word was a plausible vs. an implausible continuation of the sentence). The results showed that identity primes, but not associates or synonyms, primed target words in early measures of processing like first fixation and gaze duration. Plausibility effects tended to emerge in later measures of processing (e.g., on total reading time), although some evidence was obtained for early effects of semantic plausibility. We propose that priming in naturalistic conditions is not caused by intralexical spreading activation or access to precompiled schemas. PMID- 11196065 TI - One frog, two frog, red frog, blue frog: factors affecting children's syntactic choices in production and comprehension. AB - Two experiments are reported which examine children's ability to use referential context when making syntactic choices in language production and comprehension. In a recent on-line study of auditory comprehension, Trueswell, Sekerina, Hill, and Logrip (1999) examined children's and adults' abilities to resolve temporary syntactic ambiguities involving prepositional phrases (e.g., "Put the frog on the napkin into..."). Although adults and older children used the referential context to guide their initial analysis (pursuing a destination interpretation in a one frog context and a modifier interpretation in a two-frog context), 4 to 5-year olds' initial and ultimate analysis was one of destination, regardless of context. The present studies examined whether these differences were attributable to the comprehension process itself or to other sources, such as possible differences in how children perceive the scene and referential situation. In both experiments, children were given a language generation task designed to elicit and test children's ability to refer to a member of a set through restrictive modification. This task was immediately followed by the "put" comprehension task. The findings showed that, in response to a question about a member of a set (e.g., "Which frog went to Mrs. Squid's house?"), 4- to 5-year-olds frequently produced a definite NP with a restrictive prepositional modifier (e.g., "The one on the napkin"). These same children, however, continued to misanalyze put instructions, showing a strong avoidance of restrictive modification during comprehension. Experiment 2 showed that an increase in the salience of the platforms that distinguished the two referents increased overall performance, but still showed the strong asymmetry between production and comprehension. Eye movements were also recorded in Experiment 2, revealing on-line parsing patterns similar to Trueswell et al.: an initial preference for a destination analysis and a failure to revise early referential commitments. These experiments indicate that child-adult differences in parsing preferences arise, in part, from developmental changes in the comprehension process itself and not from a general insensitivity to referential properties of the scene. The findings are consistent with a probabilistic model for uncovering the structure of the input during comprehension, in which more reliable linguistic and discourse-related cues are learned first, followed by a gradually developing ability to take into account other more uncertain (or more difficult to learn) cues to structure. PMID- 11196066 TI - Locality and parsing complexity. AB - Two experiments, an off-line acceptability judgment study and an on-line self paced reading experiment, were conducted to tackle the question of locality-based preferences in sentence processing. The material consisted of German verb-final sentences containing a relative clause that was either host adjacent or extraposed. While the off-line data seem to reflect locality based integration cost, the on-line data revealed a highly different picture. It is argued that, in the present constructions at least, locality is relevant for production rather than perception. In perception, heads can be anticipated through incremental integration of their arguments. PMID- 11196067 TI - Wide-coverage probabilistic sentence processing. AB - This paper describes a fully implemented, broad-coverage model of human syntactic processing. The model uses probabilistic parsing techniques, which combine phrase structure, lexical category, and limited subcategory probabilities with an incremental, left-to-right "pruning" mechanism based on cascaded Markov models. The parameters of the system are established through a uniform training algorithm, which determines maximum-likelihood estimates from a parsed corpus. The probabilistic parsing mechanism enables the system to achieve good accuracy on typical, "garden-variety" language (i.e., when tested on corpora). Furthermore, the incremental probabilistic ranking of the preferred analyses during parsing also naturally explains observed human behavior for a range of garden-path structures. We do not make strong psychological claims about the specific probabilistic mechanism discussed here, which is limited by a number of practical considerations. Rather, we argue incremental probabilistic parsing models are, in general, extremely well suited to explaining this dual nature- generally good and occasionally pathological--of human linguistic performance. PMID- 11196068 TI - Evaluation of a highly specific functional test for the detection of factor V Leiden. AB - In the present study, a new functional test for the detection of increased resistance of coagulation factor V to degradation by activated protein C (factor V Leiden mutation) was evaluated. The STA-STACLOT APC-R Test (Diagnostica Stago, Asnieres, France) is based on the specific activation of factor X by Crotalus viridis helleri snake venom. The results are given as clotting time in seconds of the patient's plasma in the presence of venom and activated protein C. The intra assay coefficient of variation was 2.17% (n=20) for samples within the normal range, and 1.70% and 1.42% (n=20) for the plasma of a heterozygous or a homozygous carrier of the factor V Leiden mutation, respectively. The inter-assay coefficient of variation (n=10) was 7.75% for the plasma of a healthy donor, 5.05% for the plasma of a heterozygous carrier and 3.38% for the plasma of a homozygous individual. The normal range (5th-95th percentile) of 136.4 s-174.7 s was derived from the clotting time of the plasma of 38 healthy controls. Values below 136 s were found in every sample from patients carrying the factor V Leiden mutation (n=52), whereas no patient with protein C (n=11) or protein S deficiency (n=10) had reduced clotting times. Homozygous carriers of the factor V Leiden mutation had clotting times shorter than 66.0 s and heterozygous carriers had clotting times longer than 80.0 s. Thus, based upon the individual clotting time, patients homozygous for factor V Leiden mutation could easily be distinguished from normals or heterozygous individuals. The influence of coagulation factor X, V, or II deficiency on the STACLOT APC-R Test was evaluated and revealed prolonged clotting times at factor V activities below 50%. In the presence of lupus anticoagulant the specificity of the STA-STACLOT APC-R Test was clearly decreased. In the present study, we clearly show that the STA-STACLOT APC-R Test is able to discriminate carriers of the factor V Leiden mutation from healthy controls or patients with protein C or protein S deficiency. PMID- 11196069 TI - The mechanism of action of angiotensin II is dependent on direct activation of vascular smooth muscle carbonic anhydrase I. AB - Our previous studies have shown that angiotensin II increases carbonic anhydrase activity both in vitro and in vivo. In this study we investigated in vitro the effect of angiotensin II on carbonic anhydrase I and II from erythrocytes and on arteriolar vascular smooth muscle carbonic anhydrase I. We also studied in vitro and in vivo the effect of angiotensin II receptor blockers (irbesartan and candesartan) on purified carbonic anhydrase I and II, on vascular smooth muscle carbonic anhydrase I and on arterial blood pressure in humans and in animals. In vitro results showed that angiotensin II is a direct and stronger activator of carbonic anhydrase I than II. Angiotensin II receptor blockers reduced mainly carbonic anhydrase I activity and completely antagonized the activating effect of angiotensin II both on purified and on vascular smooth muscle carbonic anhydrase I. Our in vivo experiments showed that irbesartan and candesartan are powerful inhibitors of carbonic anhydrase I both in erythrocytes (in humans) and in vascular smooth muscles (in animals). In humans, irbesartan and candesartan progressively reduce arterial blood pressure in hypertensive subjects, in parallel with progressive reduction of erythrocyte carbonic anhydrase I activity. We believe that angiotensin II could have a dual mechanism of action: (1) angiotensin interacting with its receptor to form a stimulus-receptor complex; (2) the same stimulus directly acts on the carbonic anhydrase I isozyme (which might be coupled with angiotensin II receptors), ensuring an adequate pH for stimulus-receptor coupling for signal transmission into the cell and hence vasoconstriction. PMID- 11196070 TI - Nitric oxide production during bacterial and viral meningitis in children. AB - Nitric oxide is very likely to play a role in physiopathological mechanisms of bacterial meningitis. As shown by in vitro studies, nitric oxide is toxic to endothelial cells, as well as to neurones, and thus may be responsible for neurological sequelae in bacterial meningitis. Increased level of nitric oxide can also inhibit mitochondrial respiration, enhancing anaerobic glycolysis. Twenty-seven children with documented bacterial meningitis, 73 with viral (mumps and enteroviral) meningitis, and 51 controls were studied. All children with bacterial meningitis were given cefotaxime (200 mg/kg per day). Glucose and protein concentrations and cerebrospinal fluid cell counts were determined routinely, as well as nitrite and nitrate levels. The levels of nitrite and nitrate in cerebrospinal fluid on admission were higher in patients with bacterial meningitis than in controls or in children with viral meningitis. In 10 patients, dexamethasone therapy (0.4 mg/kg every 12 h for 2 days) was started about 10 min before the first antibiotic dose. A significantly lower nitrite concentration was observed after 24-48 h of treatment compared with non-steroid treated patients. Significant positive correlations between the nitrite and granulocyte counts and the protein concentration in cerebrospinal fluid were found in all patients with meningitis. Increased nitric oxide production in cerebrospinal fluid during the acute phase of bacterial meningitis may result from the inflammatory process and tissue injury. Dexamethasone administered before the first parenteral antibiotic dose seems to reduce nitric oxide production in the cerebrospinal fluid during bacterial meningitis. PMID- 11196071 TI - Oxidized low-density lipoprotein is localized in the ventricles of hearts from patients with coronary heart disease. AB - The present study was designed to investigate whether oxidized low-density lipoprotein is accumulated in the left and right ventricular walls of patients with coronary heart disease (n=10) compared with patients with dilated cardiomyopathy (n=9) or healthy heart donors (controls, n=5). Sections from both ventricles of explanted hearts and coronary arteries of the same patients were analyzed by semiquantitative immunohistochemistry for the presence of oxidized low-density lipoprotein. Oxidized low-density lipoprotein was enriched in the left and right ventricular walls from coronary heart disease patients compared with patients with dilated cardiomyopathy (P=0.0012 for left ventricle and P=0.103 for right ventricle) or controls (P=0.0012 for the left ventricle and P<0.05 for the right ventricle). The accumulation of oxidized low-density lipoprotein was higher in the left than in the right ventricles in all three groups. Positive immunoreactivity for oxidized low-density lipoprotein was mainly identified in the endocardium and the subendocardial areas of the ventricles and co-localized with macrophages. Accumulation of oxidized low-density lipoprotein in the ventricles significantly correlated with the enrichment in the respective coronary arteries, whereas only poor correlations were observed between various hemodynamic parameters and ventricular oxidized low-density lipoprotein accumulation. Ventricular accumulation of oxidized low-density lipoprotein seems to be a generalized pathophysiological process which does not exclusively involve the coronary arteries. Higher oxidative stress in combination with impaired oxygen supply in the endocardium could have favored low-density lipoprotein deposition and oxidation. PMID- 11196072 TI - Serum lipoprotein profile in patients with cancer. A comparison with non-cancer subjects. AB - The association of cancer with low serum total cholesterol is well established. Less clear is the relationship of cancer with the cholesterol distribution among the different lipoprotein classes. Conflicting results have been reported on low density lipoprotein cholesterol, high-density lipoprotein cholesterol and serum triglyceride levels in different types of tumor. Total serum cholesterol, low density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and serum triglycerides were analyzed in 530 patients with newly diagnosed cancer (97 with hematological malignancies, 92 with tumor of the lung, 108 of the upper digestive system, 103 of colon, 32 of breast, and 98 of the genitourinary system) and in 415 non-cancer subjects. Anthropometric (body mass index) and biochemical (serum albumin) indices of nutritional status were also determined in all subjects. Total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein cholesterol, serum albumin, and body mass index were significantly lower in cancer than in non cancer-subjects. The lowest values of total cholesterol, low density lipoprotein-cholesterol and high-density lipoprotein-cholesterol were recorded in patients with hematological malignancies and the highest in patients with breast tumor. All the cancer groups, with the exception of women with breast cancer, showed significantly lower total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein-cholesterol than age- and sex-matched non-cancer subjects. Multiple regression analysis with low-density lipoprotein cholesterol, high-density lipoprotein-cholesterol, and triglycerides as dependent variables and sex, age, body mass index, albumin, and cancer (dummy variable) as independent variables, showed that cancer was independently associated with low levels of low-density lipoprotein-cholesterol and high-density lipoprotein cholesterol and with high values of serum triglycerides. Total cholesterol, low density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, serum triglycerides, body mass index and serum albumin were significantly lower in patients with metastatic than in patients with non-metastatic solid tumor. The significant difference in low-density lipoprotein-cholesterol and serum triglycerides between patients with metastatic and non-metastatic cancer was lost when lipoprotein cholesterol and serum triglyceride levels were adjusted for nutritional variables. The lipid profile in cancer patients is characterized by low low-density lipoprotein-cholesterol, low high-density lipoprotein-cholesterol and relatively high serum triglycerides. The abnormality is a common feature of both hematological and solid tumors and is not entirely explained by poor nutrition. PMID- 11196073 TI - Role of platelets in tissue factor expression by monocytes in normal and hypercholesterolemic subjects. In vitro effect of cerivastatin. AB - Thrombosis is a complication of atherosclerosis and monocytes play a determinant role either in the progression of atherosclerotic plaque or in blood coagulation by way of tissue factor expression. Platelets play a direct role in thrombosis and a hyperfunctional state has been described in hypercholesterolemic subjects. Moreover, platelets seem to be able to enhance monocyte activity. Cholesterol lowering molecules (statins) are reported to reduce cardiovascular risk, either by decreasing the circulating level of cholesterol or by non-lipidic actions such as the reduction of monocyte and platelet activity. The aim of our study was to investigate the influence of platelets on the expression of tissue factor by monocytes and the effect induced by cerivastatin. We measured tissue factor levels by ELISA and the procoagulant activity of stimulated monocytes by a clotting assay on cellular preparations and whole blood in 40 hypercholesterolemic subjects (22 male, 18 female, mean age 52.7 +/- 12 years, total cholesterol 251.6 +/- 19.9 mg/dl) before and after cerivastatin addition. Tissue factor expression was enhanced in hypercholesterolemic subjects compared with normal subjects (31.6 +/- 7.6 vs. 23 +/- 5.8 pg/cells, P < 0.01). The presence of platelets increased the amount of tissue factor (55.3 +/- 7.3 pg/cells, P < 0.001) and cerivastatin reduced the expression of tissue factor in isolated monocytes, in the mixed cellular system, and in whole blood (19.6 +/- 4.1 pg/cells, P < 0.001). In conclusion, tissue factor expression by monocytes is enhanced in hypercholesterolemic subjects compared with normal controls. Platelets enhance monocyte production of tissue factor, and cerivastatin is able to counteract this prothrombotic mechanism. PMID- 11196074 TI - Responses of the skin microcirculation to acetylcholine and to sodium nitroprusside in chronic uremic patients. AB - The aim of the present study was to assess the endothelial function of the microcirculation in chronic renal failure. We investigated the responses of the cutaneous blood flow to locally delivered acetylcholine and sodium nitroprusside in uremic patients. The study included 60 chronic uremic patients: 40 patients with a creatinine clearance of 4-25 ml/min were on conservative treatment and 20 patients were on maintenance hemodialysis. The changes in skin blood flow following iontophoretic delivery of acetylcholine (an endothelium-dependent vasodilator) and sodium nitroprusside (an endothelium-independent vasodilator) were measured by laser Doppler flowmetry. Acetylcholine induced a progressive increase in blood flow in both groups, reaching approximately 100% of the maximal hyperemic response obtained by sodium nitroprusside delivery. The percent increase in blood flow from baseline was lower in hemodialysis patients than in patients on conservative treatment, after both acetylcholine (550 +/- 44 vs. 718 +/- 61%, P < 0.05) and sodium nitroprusside (553 +/- 46 vs. 735 +/- 69%, P < 0.05) delivery. In the hemodialysis group, the hyperemic responses to acetylcholine and sodium nitroprusside did not improve after the hemodialysis session. Hence, the hyperemic responses of the skin microcirculation are lower in hemodialysis patients than in patients on conservative treatment, and did not ameliorate after hemodialysis. It seems to be independent of endothelial dysfunction, and associated with the severity of uremia and with the maintenance hemodialysis treatment. This microcirculatory abnormality is in keeping with the arterial stiffness and vascular wall damages described in dialysis patients, which contribute to the cardiovascular morbidity of chronic uremia. PMID- 11196075 TI - Pulmonary effects of inhaled ultrafine particles. AB - INTRODUCTION AND OBJECTIVES: Recent epidemiological studies have shown an association between increased particulate urban air pollution and adverse health effects on susceptible parts of the population, in particular the elderly with pre-existing respiratory and cardiovascular diseases. Urban particles consist of three modes: ultrafine particles, accumulation mode particles (which together form the fine particle mode) and coarse mode particles. Ultrafine particles (those of < 0.1 micron diameter) contribute very little to the overall mass, but are very high in number, which in episodic events can reach several hundred thousand/cm3 in the urban air. The hypothesis that ultrafine particles are causally involved in adverse responses seen in sensitive humans is based on several studies summarized in this brief review. METHODS AND RESULTS: Studies on rodents demonstrate that ultrafine particles administered to the lung cause a greater inflammatory response than do larger particles, per given mass. Surface properties (surface chemistry) appear to play an important role in ultrafine particle toxicity. Contributing to the effects of ultrafine particles is their very high size-specific deposition when inhaled as singlet ultrafine particles rather than as aggregated particles. It appears also that ultrafine particles, after deposition in the lung, largely escape alveolar macrophage surveillance and gain access to the pulmonary interstitium. Inhaled low doses of carbonaceous ultrafine particles can cause mild pulmonary inflammation in rodents after exposure for 6 h. Old age and a compromised/sensitized respiratory tract in rodents can increase their susceptibility to the inflammatory effects of ultrafine particles significantly, and it appears that the aged organism is at a higher risk of oxidative stress induced lung injury from these particles, compared with the young organism. Results also show that ultrafine particle effects can be significantly enhanced by a gaseous co-pollutant such as ozone. CONCLUSIONS: The studies performed so far support the ultrafine particle hypothesis. Additional studies are necessary to evaluate mechanistic pathways of responses. PMID- 11196076 TI - A follow-up study on occupational exposure to inhaled anaesthetics in Eastern European surgeons and circulating nurses. AB - OBJECTIVE: Although no dose-response relationship exists for the health risks associated with the occupational exposure to inhaled anaesthetics, public health authorities recommend threshold values. The aim of the present study was to assess whether and to what extent these threshold values are exceeded in surgeons and circulating nurses of an Eastern European university hospital, before and after measures had been taken to reduce occupational exposure. METHODS: At nine workplaces, occupational exposure to nitrous oxide and the volatile anaesthetic used (halothane or isoflurane) was measured within the breathing zones of surgeons and circulating nurses by means of photoacoustic infrared spectrometry. The measurements were carried out in 1996 and were repeated in 1997 after the installation of active scavenging devices at five workplaces, and an air conditioning system at one workplace. RESULTS: Occupational exposure to nitrous oxide and halothane or isoflurane was lower in 1997 compared with that of 1996. In 1996, 89% of the nitrous oxide values were above the European threshold value of 100 ppm, whereas in 1997 approximately 50% were above this limit. In 1996 the majority of the measurements for the volatile anaesthetics were already below 5 ppm halothane and 10 ppm isoflurane and the number of measurements exceeding these limits was further reduced in 1997. CONCLUSION: The measures taken were effective in reducing waste gas exposure. Nevertheless, further efforts are necessary, especially for nitrous oxide, to reach Western European standards and to minimise possible health risks. These efforts comprise the installation of (active) scavenging devices, air-conditioning systems and new anaesthesia machines at all workplaces, the use of low-flow anaesthesia, the replacement of inhaled anaesthetics by intravenous anaesthetics and an appropriate working technique. PMID- 11196077 TI - Gender differences in upper extremity musculoskeletal complaints in the working population. AB - OBJECTIVES: This study analysed the association between gender and upper extremity musculoskeletal complaints, among the general working population and in various occupational groups. The hypothesis was tested whether the higher risk for women in the general working population for these complaints could partly be explained by differences in the distribution of men and women in occupations with different risks for the onset of upper extremity musculoskeletal complaints. METHODS: The data for this study came from cross-sectional questionnaire data from 16,874 employees categorised in 21 different occupational classes. Associations between gender and complaints of the upper extremities were analysed for the total study sample and for each occupational class separately. An adjustment was made for the variable 'occupational class' in the final model in order to study the impact of occupational gender segregation on gender differences in upper extremity complaints in the working population. RESULTS: In the total study sample, significantly higher risks of complaints of the neck, shoulder, elbow, and wrist among the women were observed. Within many occupational classes, women reported significantly higher risks than did men, in particular for complaints of the neck and shoulder. Adjustment for occupational class showed increased risks for female workers for complaints of the neck, shoulder, elbow, and wrist, hence, rejecting our hypothesis on occupational gender segregation as an explanation for the higher risks for upper extremity complaints among women in the general working population. CONCLUSIONS: This study confirmed the presence of gender differences in upper extremity musculoskeletal complaints among the working population and in many occupational classes, with female workers having the higher risk. The results, however, do not lend support to a differential occupational exposure theory as an explanation for the higher risks for these complaints among women in the general working population. Careful consideration of gender influence in ergonomic epidemiological studies is recommended. PMID- 11196078 TI - Biological monitoring of workers exposed to ethylbenzene and co-exposed to xylene. AB - OBJECTIVE: Ethylbenzene is an important constituent of widely used solvent mixtures in industry. The objective of the present study was to provide information about biological monitoring of occupational exposure to ethylbenzene, and to review the biological limit values corresponding to the threshold limit value of ethylbenzene. METHODS: A total of 20 male workers who had been exposed to a mixture of ethylbenzene and xylene, through painting and solvent mixing with commercial xylene in a metal industry, were recruited into this study. Environmental and biological monitoring were performed during an entire week. The urinary metabolites monitored were mandelic acid for ethylbenzene and methylhippuric acid for xylene. Correlations were analyzed between urinary metabolites and environmental exposure for ethylbenzene and xylene. The interaction effects of a binary exposure to ethylbenzene and xylene were also investigated using a physiologically based pharmacokinetic (PBPK) model. RESULTS: The average environmental concentration of organic solvents was 12.77 ppm for xylene, and 3.42 ppm for ethylbenzene. A significant correlation (R2 = 0.503) was found between environmental xylene and urinary methylhippuric acid. Urinary level of methylhippuric acid corresponding to 100 ppm of xylene was 1.96 g/g creatinine in the worker study, whereas it was calculated as 1.55 g/g creatinine by the PBPK model. Urinary level of mandelic acid corresponding to 100 ppm of ethylbenzene was found to be 0.7 g/g creatinine. PBPK results showed that the metabolism of ethylbenzene was highly depressed by co-exposure to high concentrations of xylene leading to a non-linear behavior. CONCLUSIONS: At low exposures, both methylhippuric acid and mandelic acid can be used as indicators of commercial xylene exposures. However at higher concentrations mandelic acid cannot be recommended as a biological indicator due to the saturation of mandelic acid produced by the co-exposure to xylene. PMID- 11196079 TI - Occupational exposure to low concentrations of carbon disulfide as a risk factor for hypercholesterolaemia. AB - OBJECTIVE: The objective of this study was to investigate the effect of occupational exposure to carbon disulfide (CS2) concentrations below threshold limit value (TLV)-time-weighted average (TWA) (31 mg/m3) on total cholesterol, blood pressure and the prevalence of coronary heart disease (CHD). METHODS: A cross-sectional study involving 141 viscose rayon workers (64 men), and 141 age- and gender-matched controls without occupational contact with noxious chemicals, was carried out. The probability for CHD was determined by means of the WHO questionnaire and was 12-lead electrocardiography-coded using Minnesota criteria. Blood pressure was measured by the standardized method of the WHO and blood was examined for total cholesterol. A cumulative exposure index (CS2 index) was calculated for each worker by multiplying the number of years held in a particular job, by the CS2 concentrations in that job-environment. According to the CS2 index, the exposed workers were distributed into two groups: group 1 (CS2 index < 100) and group 2 (CS2 index > or = 100). RESULTS: Depending on the job and specific work place the CS2 concentrations were between 1 and 30 mg/m3. Cholesterol levels were significantly higher in the exposed group (4.9 +/- 0.7) compared with the controls (4.6 +/- 0.7). Adjustment for age, smoking, body-mass index (BMI) and gender showed the significant effect of the CS2 index on the total cholesterol (P < 0.001). The prevalence of hypercholesterolaemia was significantly higher in the exposed group (42.6%), compared with the controls (26.2%); odds ratio (OR) (adjusted for potential confounders) was 2.56, 95% CI 1.47-4.46. Logistic regression showed a significantly increased risk for elevated cholesterol in group 2 (OR 5.52; 95% CI 2.81-10.83). No significant effect of CS2 index on blood pressure and CHD prevalence was found. CONCLUSIONS: The results of our study show that occupational exposure to CS2 concentrations below 31 mg/m3 and a CS2 index > 100 may increase total cholesterol. Our results imply that even the CS2 concentrations below TLV-TWA may produce morbid changes, and suggest the mechanism of the effect of CS2, leading to lipid metabolism disturbances and acceleration of atherosclerosis. PMID- 11196080 TI - Acute effects on the human EEG after an external exposure to 200 ppm methanol. AB - OBJECTIVES: Even low concentrations of organic solvents may cause acute effects on the human central nervous system. The German MAK (threshold limit value) of methanol is 200 ppm. The aim of this study was to investigate whether acute exposure to 200 ppm methanol causes adverse effects, measured by EEG, and moreover, whether it is possible to differentiate between sedative and excitatory effects with this method. METHODS: Twelve healthy subjects were exposed for 4 h to 200 ppm and to 20 ppm (control) in an exposure chamber in a cross-over design. The EEG was recorded before (reference) and at the end of each exposure with, the subject's eyes closed and opened and during a choice reaction test (color word stress test). Spectral power was calculated by fast Fourier transformation. Subjective symptoms and effects of blinding with 20 ppm methanol were assessed by questionnaires. RESULTS: The study was a single-blind one. During subjects' exposure to 200 ppm, their scores for prenarcotic and irritating symptoms were not different from controls. In the closed-eye condition of subjects, the spectral power of the theta-band and of some electrodes of the delta-band was significantly less at the end of exposure to 200 ppm, than that of controls. In the open-eye condition and during the color word stress test no significant changes were found. CONCLUSION: The changes in the theta-band suggest a slight excitatory effect of 200 ppm methanol. The effect was weak, as scores of acute symptoms did not change. With respect to our results, it is not necessary for the MAK value to be decreased. PMID- 11196081 TI - Performance assessment of a passive sampler in industrial atmospheres. AB - In this work we investigate the performances of a passive sampler (GABIE badge) in industrial atmospheres, in accordance with the general specifications of the EN 838 standard. The field experiment was carried out in a paint-manufacturing factory producing a large number of pollutants at the workplaces. A comparison was performed between the results obtained by passive sampling and the conventional tube/pump method (reference method) on nine solvents usually encountered in the different workshops: n-butanol, isobutanol, toluene, ethylbenzene, m-xylene, methylisobutylketone, methylethylketone (MEK), ethyl acetate, butyl acetate. Results were compared by use of the distribution of the relative difference between badge "passive sampling" and tube "active sampling" results (with the latter considered as the reference method). In general, results revealed good agreement between passive and active sampling (except in the case of MEK) and confirmed the accuracy of sampling rates determined for the GABIE sampler. Bias was generally low and variability could be considered to be satisfactory (generally < 20% with a maximum of 30% for ethylbenzene). For MEK, strong bias was noted together with probable underestimation of the tube results. Additional results lead us to suggest that this phenomenon could be due to poor desorption of the SKC tubes by carbon disulphide (CS2); (quantitative recovery for MEK is in fact possible using other desorption solvents). PMID- 11196082 TI - Factors affecting FEV1 in workers with potroom asthma after their removal from exposure. AB - OBJECTIVE: In this study the relationship has been studied between exposure time and potential prognostic factors and FEV1 percent predicted (FEV1-% pred) in workers with potroom asthma, after their transfer from exposure to exposure-free departments. METHODS: Between 1970 and 1990 in a Dutch aluminium-production plant, 179 workers had been diagnosed as having potroom asthma. We carried out a follow-up study (n = 122) in the population still present at the factory 5 years after their relocation to an exposure-free department. In this study population, we examined the relationship between FEV1-% pred at follow-up, and exposure time: the time interval between start of exposure and diagnosis. To correct for confounding factors, we included age, pre-employment FEV1-% pred, allergy, medical treatment, and smoking in the analysis. RESULTS: The mean FEV1-% pred at follow-up was within the normal range (90.3, SD 13.5). Long exposure time was significantly associated with a low FEV1-% pred at follow-up (P = 0.0046). Adjustment was necessary for pre-employment FEV1-% pred and current smoking as confounding factors. CONCLUSION: Long duration of exposure is a factor affecting FEV1 in workers with potroom asthma. The results of this study give support for additional preventive measures to be taken, such as early recognition of work related respiratory complaints and repeated education. PMID- 11196083 TI - Urinary 1-hydroxypyrene and 2-naphthol concentrations in male Koreans. AB - OBJECTIVE: Urinary 1-hydroxypyrene (1-OHP) has been used as a biological marker of exposure to polycyclic aromatic hydrocarbons (PAHs), and urinary 2-naphthol is suggested as a new marker for route-specific exposure to airborne PAHs. We analyzed urinary 1-OHP and 2-naphthol concentrations in 292 male Koreans (129 university students and 163 shipyard workers) to define the distribution pattern in Koreans with no or low occupational exposure to PAHs. METHOD: Histories of cigarette smoking and the eating of PAH-containing foods were obtained by a self administered structured questionnaire. Urine samples were collected and urinary 1 OHP and 2-naphthol concentrations were measured using high-performance liquid chromatography (HPLC). RESULTS: The arithmetic (geometric) means of urinary 1-OHP and 2-naphthol concentrations for all students, expressed as micromoles per mole of creatinine, were 0.04 (0.04) and 3.12 (2.22), for non-smokers 0.03 (0.03) and 1.78 (1.30) and for smokers 0.05 (0.03) and 4.36 (3.62), respectively. Among shipyard workers, the arithmetic (geometric) means of urinary 1-OHP and 2 naphthol concentrations were 0.69 (0.31) and 4.37 (2.62) for all, 0.27 (0.18) and 2.46 (1.16) for nonsmokers, and 0.97 (0.44) and 5.60 (4.44) for smokers, respectively. Mean urinary 1-OHP and 2-naphthol concentrations differed significantly between nonsmokers and smokers both in students and in shipyard workers. In smokers, some variables related to smoking habit were positively correlated with urinary 1-OHP and with 2-naphthol concentrations. The latter showed better correlations with the variables related to smoking amount than the former. None of the food-related factors was significantly correlated with urinary 1-OHP or 2-naphthol concentration. CONCLUSION: These results suggest that urinary 2-naphthol concentration is more sensitively affected by smoking status than urinary 1-OHP concentration and that urinary 2-naphthol is a sensitive marker for low-level inhalation of PAHs. PMID- 11196084 TI - Adjustment to concentration-dilution of spot urine samples: correlation between specific gravity and creatinine. AB - OBJECTIVE: Spot urine samples were investigated to determine correlations between urinary creatinine and specific gravity, and intra- and inter-day variations other than gender- and age-dependence of urinary concentrations. METHODS: Urinary creatinine concentrations and specific gravity were determined in 534 spot samples (385 from men and 149 from women). Subjects' ages ranged between 18 and 68 years. Spot urine samples were also collected from 14 male subjects before and after a 1-week work-shift for the evaluation of intra- and inter-day variations of creatinine and specific gravity. RESULTS: In spot samples, creatinine concentrations ranged between 0.16 and 4.36 g/l and specific gravity between 1.002 and 1.037. A high correlation (r = 0.82, P < 0.001) was observed between creatinine and specific gravity; male subjects showed significantly higher values of creatinine (P < 0.001) than did female subjects (1.90 +/- 0.74 and 1.41 +/- 0.72 g/l, respectively) and specific gravity (1.023 +/- 0.006 and 1.020 +/- 0.007, respectively). In addition, creatinine but not specific gravity significantly decreased (P < 0.02) in subjects older than 50 years, compared with those under 40. CONCLUSIONS: Results confirm the gender-dependence of creatinine concentrations in spot specimens and also show age-dependence, indicating the need for these aspects to be considered when the range of acceptable samples is to be set. No significant intra- or inter-day variations were observed for the two parameters. Lastly, the possibility of a comparison of differently adjusted values was indicated by a conversion formula derived from adjustments to creatinine and the corresponding specific gravity of a hypothetical urinary value, as follows: specific gravity adjusted values = 1.48 x creatinine adjusted values. PMID- 11196085 TI - Evaluation of occupational health service systems in small- and medium-sized industries in Korea. AB - OBJECTIVES: To establish a system of analytical methodology that can be used to evaluate an occupational health service system, to evaluate the performance of different types of the system in small- and medium-sized industries using the evaluation model, and to identify factors which influence the performance of an occupational health service system. METHODS: The input-output-outcome aspects of two different systems, capitation-based Group health services and fee-for-service based Individual health services, were examined, based on a causal model. Each causal relationship in the model was tested for its statistical significance by the linear regression technique based on the ordinary least square method. Data from 16 enterprises in the Group-type, 17 enterprises in the Individual-type, and 32 enterprises in the Transitional Group-type were used in the analyses. RESULTS: In the Group model, enterprises utilized fewer resources for occupational services, their workers were provided with more services when services such as medical examinations were supplied directly by the system, and they had worse outcome measures of health and industrial injuries. The latter was the result of less input and fewer services, the supply of which was not within the direct control of the system, such as compliance with the recommendation to install machine safety devices and the proper maintenance and operation of these devices. CONCLUSIONS: Although study results revealed problem areas in the performance of the Group system, the study found a potential for an effective and efficient system in the Group-type with efforts geared to the better follow-up of work environment problems. PMID- 11196087 TI - [Value of chemotherapy in curative therapy of head and neck therapy]. PMID- 11196088 TI - [Reports from the annual meeting of the German Society of Otorhinolaryngology, Head and Neck Surgery in Berlin]. PMID- 11196086 TI - Mechanism of refractory ceramic fiber- and rock wool-induced cytotoxicity in alveolar macrophages. AB - OBJECTIVES: Man-made vitreous fibers (MMVFs) can induce cytotoxicity in a way similar to that of other particles, including silica and asbestos fibers. However, as yet the mechanism of MMVF-induced cytotoxicity is still not clear. This report aims to clarify the mechanism of MMVF-induced cytotoxicity in the alveolar macrophage (AM). In this mechanism, an attempt to prove the involvement of the adenosine triphosphate (ATP) generation system and the polyinosinic acid inhibitable scavenger receptors was made. METHODS: Several parameters were observed for cytotoxicity, such as cell viability, the release of lactic dehydrogenase (LDH) and ATP levels in rat AM's that were treated with refractory ceramic fibers (RF2) and rock wool (RW1). A specially designed ATP generation system was used to determine the effect of MMVF on ATP generation. A scavenger receptor ligand was applied to evaluate the relationship between scavenger receptors and MMVF-induced ATP depletion. RESULTS: A 3-(4,5-dimethylthiazol)-2,5 diphenyl tetrazolium bromide (MTT) assay indicated that both RF2 and RW1 caused a decrease in cell viability and this decrease was concentration-dependent. RF2 and RW1 increased the release of LDH with increasing fiber concentration. From these parameters, RF2 was shown to exhibit greater cytotoxicity than did RW1. Both fibers decreased the intracellular ATP content and this decrease was concentration-dependent. The decrease was more pronounced in RW1 than in RF2 at all fiber concentrations. These fibers suppressed succinate-triggered oxygen consumption. Polyinosinic acid, a ligand of the scavenger receptor, inhibited the MMVF-induced decrease in ATP concentration. CONCLUSION: These results suggest that RF2 and RW1 can induce cytotoxicity and ATP depletion in the AM through the polyinosinic acid-inhibitable scavenger receptor. ATP depletion was the important factor in MMVF cytotoxicity, especially by RW1. PMID- 11196089 TI - [Congenital hearing disorders in children. 1: Acquired hearing disorders]. AB - The results of international investigations on connatally acquired hearing loss are compared with the data of the German Registry on Childhood Hearing Loss (4058 cases). The connatal hearing disorders have shown a notable change in the last years regarding to aetiology and prevalence. In contrast to countries of the third world in developed nations the prevalence of permanent childhood hearing loss has been reduced down to 1 in 1.000 births. The results let assume a prevalence of approximately 1:1.200 births in Germany. For instance the number of rubella embryopathia decreased effectively. In contrast CMV infections and alcohol fetopathia are playing an increasing role. In the patients of the German Registry on Childhood Hearing Loss the percentage of certainly progressive hearing loss is 10.3 within the 4058 children with permanent hearing impairment. Diagnostic procedures first of all for the early diagnosis of CMV but also of toxoplasmosis are considerable because these infections may result in treatable hearing loss. Also consequent hearing tests are demanded in children with alcohol fetopathia. PMID- 11196090 TI - [An assessment of tinnitus retraining therapy]. AB - Based on the neurophysiological model of tinnitus developed by Jastreboff and Hazell [39] there have been some important developments in understanding and therapy of tinnitus over the last decade. The clinical applications of this model are known as "tinnitus retraining therapy", which has the objective of reducing both the distress associated with tinnitus and the tinnitus perception itself. As a form of systematic, repeated and skilled counselling over a long period of up to 2 years supported by sound therapy (hearing aid or noise generator) the evidence for their high degree of effectiveness is overwhelming. On the basis of a "German concept" of tinnitus retraining therapy developed and proposed by the ADANO (Arbeitsgemeinschaft deutschsprachiger Audiologen und Neurootologen) the current status of this treatment will be briefly reviewed including some actual studies of Goebel et al. [14] that confirm the world wide critical comments on the recent developments in the management of tinnitus especially with regard to tinnitus retraining therapy [79]. PMID- 11196091 TI - [Quality assurance in ENT tumor surgery]. AB - BACKGROUND AND OBJECTIVE: Quality control is of special importance in head and neck oncology since the quality of medical care constitutes a vital parameter for the diseased patient. In contrast to other medical specialties, no quality assurance program for head and neck cancer patients has yet been established in Germany. Therefore, a survey was conducted to assess the quality assurance instruments that are in use today in otorhinolaryngology-head and neck (ORL-HNS) centers. PATIENTS AND METHODS: In a nationwide survey, questionnaires were sent out to 146 German ORL-HNS departments (the return rate was 75%). RESULTS: 56% of all departments apply dedicated quality assurance processes, and 38% have appointed a formal quality assurance officer. Interdisciplinary oncological conferences are held in the vast majority of all departments with the participation of radiation oncologists in 86 (78%), medical oncologists in 84 (76%), diagnostic radiologists in 82 (74%), and pathologists in 73 (66%). Morbidity-mortality conferences are held in seven departments (6%). A standardized follow-up of oncological patients is carried out in 95 units (86%), and 53 departments use computer-assisted data bases to organize their follow-up data (48%). A wide variety of documentation systems is in use throughout the country: 78 units (71%) offer formal follow-up to their oncological patients. CONCLUSIONS: This survey documents a wide-spread interest in quality assurance procedures. Many individual efforts are being undertaken. However, no uniform quality assurance or auditing system is currently in use in Germany nor is a commonly accepted data base available. The ability to offer oncological follow-up within the national social security system is generally considered indispensable for the maintenance of high-quality oncological care in ORL-HNS departments. PMID- 11196092 TI - [Morphological connections between the Hypoglassal and facial nerve in the brain stem of the rat]. AB - BACKGROUND AND OBJECTIVE: The perfect coordination and synchronization of hypoglossal and facial muscles during chewing, swallowing, breathing, and vocalization requires particular concomitant activities of the facial muscles. In contrast, no direct connection between the facial and hypoglossal nucleus on the level of the brain stem has been detected until now. PATIENTS/METHODS: Facial and hypoglossal nuclei of rats were identified on the basis of their antidromic field potential recorded after peripheral stimulation of the corresponding nerves. Stereotactically single or double fluorescence tracer injections (Biotin-Dextran, Fluorescine-Dextran, Rhodamine-Dextran, Fluoro Gold) were placed into the nuclei. RESULTS: Retrograde tracer injections into the facial nucleus consistently labeled small neurons in the hypoglossal nucleus. In reverse experiments the injection of anterograde tracers into the hypoglossal nucleus labeled fine caliber varicose nerve fibers, but no somata in the facial nucleus. Synchronous injections of different tracers into the facial and hypoglossal nucleus produced a small, but constant number of double-labeled cells in the parvocellular reticular formation. CONCLUSIONS: Both, hypoglossal interneurons projecting to the facial nucleus and neurons of the parvocellular reticular formation double projecting to the facial and hypoglossal nucleus might play an important role in coordinated orofacial movements. Moreover, both populations of neurons might be responsible for the excellent postoperative results after hypoglossal-facial anastomosis. PMID- 11196093 TI - [Pharyngolaryngoscopic findings in patients with obstructive sleep apnea syndrome and primary snoring]. AB - BACKGROUND AND OBJECTIVE: The localization of an upper airway collapse in snorers and patients suffering from obstructive sleep apnea was a subject frequently discussed in the last few years. Pharyngolaryngoscopy during sleep or drug induced sleep allows evaluation of upper airway conditions. PATIENTS/METHODS: A total of 324 patients suffering from snoring or obstructive sleep apnea underwent flexible pharyngolaryngoscopy while awake and under propofol-induced sedation in the course of routine diagnostic procedures in the sleeping lab. In this study, the results of pharyngolaryngoscopy are compared to results of the Muller maneuver and polysomnographic recordings. The therapeutic consequences of this additional investigation are discussed. RESULTS: In 95% of cases snoring was observed during drug-induced sleep. A significant discrepancy was seen between results of the endoscopy while being awake (Muller maneuver) and during drug induced sleep. The degree of collapse differed significantly in the area of the base of the tongue. Severe collapse was seen much more often with pharyngoscopy during drug-induced sleep compared to the results during the Muller maneuver. CONCLUSIONS: The collapsibility in the area of the base of the tongue correlated with higher results in the RDI (respiratory disturbance index) registered with standard polysomnography. Snoring and upper airway collapse were easily surveyed, and the pharyngolaryngoscopy during propofol-induced sleep proved to be a simple, safe, readily controllable and effective supplementary diagnostic device for the diagnosis and treatment of obstructive sleep apnea and snoring. PMID- 11196094 TI - [Significance of the SISI test within the scope of expert assessment of noise induced hearing loss]. AB - BACKGROUND AND OBJECTIVE: Proof of cochlear hearing loss is an essential prerequisite for the diagnosis of noise deafness. For this purpose, the Konigsteiner instruction leaflet (Konigsteiner Merkblatt) recommends among other items the SISI test. PATIENTS/METHODS: The results of the SISI test at 1 and 4 kHz were analysed for 100 expert opinions of noise (200 ears). RESULTS: 10% of the subjects showed at 1 and 4 kHz a positive and 44% a negative result. At 1 kHz, 46% indicated a negative result and at 4 kHz a positive result. In the group with a negative SISI test at both frequencies, 74% demonstrated characteristics of pseudohypacusis. There was no correlation between a retrocochlear hearing disorder and a negative SISI test. CONCLUSIONS: Our analysis demonstrated that the negative SISI test is more often evidence of pseudohypacusis rather than a retrocochlear disorder. Consequently, the validity of a negative SISI test is limited. PMID- 11196095 TI - [Value of a nutrition score in patients with advanced carcinomas in the area of the head and neck]. AB - BACKGROUND AND OBJECTIVE: Patients with advanced head and neck cancer often suffer from malnutrition even before the start of therapy. Hence, the demand for nutritional support increases particularly before and during radiochemotherapy. Though nutritional therapy has been shown to substantially improve individual outcome, neither the criteria for patient candidacy nor the indications for therapeutic intervention have been established. We performed a retrospective analysis to determine the indications for nutritional support and < 0 evaluate the benefits of measures actually taken against malnutrition before and during radiochemotherapy as well as perioperatively. PATIENTS/METHODS: Data taken from a prospective study for the evaluation of oral mucositis during radiochemotherapy was analysed retrospectively. To calculate the indication for nutritional support, a nutritional scoring system (Hackl) was employed for the first time, which contained biochemical and anthropometric parameters as well as the period of starvation. The results were then compared to a nutritional support program implemented by the subjective examinations of the attending physician. RESULTS: Changes in body weight and body mass index (BMI) remained the most impressive parameters. Catabolic metabolism developed preoperatively and a significant loss of whole-body protein followed surgical therapy. Clinically, the results of the nutritional score correlated with the observation of malnutrition. Furthermore, our findings suggest that nutritional therapy was commonly delayed until late in the clinical course. CONCLUSION: The results indicate the necessity of objective and reproducible diagnosis and control of malnutrition. The scoring system used may provide a useful and yet simple tool for assessing individual indications for timely nutritional support. PMID- 11196096 TI - [Objective measurement of normal nasality in the Saxony dialect]. AB - In the United States of America, the nasometer was developed by Fletcher as an objective method for measuring nasality. There are no accepted normal values for comparable test materials regarding the German language. The aim of this study was the examination of the auditively normal nasality of Saxon-speaking people with the nasometer. The nasalance of 51 healthy Saxon-speaking test persons with auditively normal nasality was measured with a model 6200 nasometer (Kay Elemetrics, U.S.A.). The text materials used were the vowels "a", "e", "i", "o", and "u", the sentences "Die Schokolade ist sehr lecker" ("The chocolate is very tasty") and "Nenne meine Mama Mimi" ("Name my mama Mimi"), and the texts of "North wind and sun", "A children's birthday", and an arbitrary selection from Strittmatter. The mean nasalance for the vowels was 17.7%, for the sentence containing no nasal sounds 13.0%, and for the sentence containing many nasal sounds 67.2%. The mean value of the texts was 33-41%. The results for the texts agreed well with the results of Reuter (1997), who examined people from the state of Brandenburg. A range from 20% to 55% is suggested as the normal value for nasalance in the German-speaking area. PMID- 11196097 TI - [Danger from exploding fireworks and blank firearms]. AB - Explosive amusement and deterrent articles such as New Year's Eve cannons and rockets, toy pistols, and blank guns are not at all harmless items. Their potential dangerousness is often extremely underestimated. Two damaging mechanisms are important: during explosions, high pressures and temperatures develop and a considerable sound pressure level can be measured. If the explosion happens near the human body (intentionally or inadvertently), not only superficial lesions can occur, but also (mainly due to contact shots) serious, deep-seated tissue damage, especially in the head and neck region with its endangered sense organs such as eye and ear, the vessels and nerves supplying the brain, the speech- and voice-forming apparatus, and in particular the face, can be the consequence. Their mutilation can lead to serious and extensive interpersonalchanges. Accidents are published in the relevant otological and forensic medical papers, but nevertheless it seems important to us to point out the dangerousness of these readily available items. PMID- 11196098 TI - [Tumor oxygenation in combined whole body hyperthermia and polychemotherapy. Studies exemplified by recurrent carcinoma of the mouth cavity]. AB - BACKGROUND AND OBJECTIVE: Previous studies have reported synergistic effects of combined hyperthermia and chemotherapy and/or irradiation. The response to irradiation and chemotherapy of well-oxygenated and vascularized tumors generally is better than that of hypoxic tumors. Therefore, tumor oxygenation is recognized as an important predictive factor in the therapy of malignant tumors. In practice, the head and neck area remains outside of the hyperthermia chamber during whole-body hyperthermia. It was the aim of this study to evaluate if the head and neck region receives sufficient warmth and, if so, if tumor oxygenation increases accordingly. PATIENTS/METHODS: Whole-body hyperthermia, as heat radiation (Enthermics Medical Systems RHS-7500), was applied to the narcotised 60 year-old male patient with a local recurrence tumor pT3 pN2b M0 squamous cell carcinoma of the oral cavity. Tumor oxygenation and temperature were measured by LICOX catheters via one-point measurement during the entire hyperthermia treatment (3.5 h). Parallelly, chemotherapy (ifosfamide/Carboplatin) was given in four cycles (one cycle/month). RESULTS: With a latency of 10 min the increase of intratumoral temperature was comparable to temperatures achieved in the esophagus. The maximum intratumoral temperature was 41.8 degrees C. The average increase in tumor oxygenation was more than 100%. The clinical outcome in the case presented was a partial tumor remission (PR). CONCLUSIONS: During combined whole-body hyperthermia and polychemotherapy, tumor oxygenation is also significantly improved in the head and neck area, despite the fact that the head and neck area remained outside the hyperthermia chamber. The intratumoral temperature was comparable to esophageal and rectal temperatures. PMID- 11196099 TI - [Determining the optimal position for snoring splints. Forced mandibular advance is not always required]. PMID- 11196100 TI - [Chronic pain at the base of the tongue. Projectile of an air rifle as a foreign body]. PMID- 11196101 TI - [Mucotympanum in cleft lip]. PMID- 11196102 TI - [Digital photo- and video-documentation]. PMID- 11196103 TI - Treating glucosphingolipid disorders by chemotherapy: use of approved drugs and over-the-counter remedies. AB - The accumulation of a glucosphingolipid (GSL) in individuals lacking an adequate level of hydrolase activity could be minimized by chemotherapeutic measures that slow the formation of the GSL and stimulate the defective hydrolase. By achieving a balance in the rates of formation and breakdown, one should be able to alleviate the symptoms of excess storage and achieve a satisfactory accommodation. While several drugs seem to be specifically suitable for this purpose, only one of these has been approved for human use. However, less effective drugs and over-the-counter substances are available for human use and may prove satisfactory for a few years until better ones are made available. The proposed materials and the evidence behind the recommendations are presented in this paper. PMID- 11196104 TI - Mutations in the low-density-lipoprotein receptor gene in German patients with familial hypercholesterolaemia. AB - Familial hypercholesterolaemia (FH) is an autosomal dominant disorder of lipid metabolism characterized by elevated low-density lipoproteins (LDL), the formation of tendon and skin xanthomata and the development of premature coronary atherosclerosis. It is caused by a defect in the receptor-mediated hepatic uptake of LDL due to mutations in the LDL receptor. In 25 FH families with a total of 160 members and in two individuals without available relatives, all of German origin, we identified LDL receptor mutations by a multiplex-PCR-based single strand conformation polymorphism method followed by direct sequencing. Of the 24 mutations found, 15 are missense mutations, 2 are nonsense mutations, 4 are small deletions or insertions leading to frameshifts, 2 are an in-frame insertion and deletion, respectively, and one is a splice site mutation. Propositi carrying mutations that are known to completely abolish receptor function (nonsense and frameshift mutations, missense mutation V480M) had significantly higher untreated total and LDL-cholesterol levels compared to those patients carrying missense and in-frame insertion mutations of unknown functional consequence, which may lead to either reduced or completely abolished receptor function (11.30+/-1.64 vs 9.76+/ 1.50 mmol/L, and 9.39+/-1.23 vs 7.99+/-1.45 mmol/L, respectively). These results confirm the clinical and molecular heterogeneity of FH and the influence of different functional classes of mutations on lipid values. PMID- 11196106 TI - Branched-chain L-amino acid metabolism in classical maple syrup urine disease after orthotopic liver transplantation. AB - We characterized the effect of orthotopic liver transplantation on the catabolism of branched-chain L-amino acids in a female patient with classical form of maple syrup urine disease. Transplantation was performed at the age of 7.4 years due to a terminal liver failure triggered by a hepatitis A infection. Since then, the patient is on an unrestricted diet and plasma concentrations of branched-chain L amino and 2-oxo acids are stable, yet at moderately increased levels (2- to 3 fold of control). L-Alloisoleucine concentrations, however, remained remarkably elevated (> 5-fold of control). In vivo catabolism was investigated by measuring the metabolic L-alloisoleucine clearance and whole-body leucine oxidation in the postabsorptive state. In an oral loading test with 580 micromol alloisoleucine per kg body wt, the L-alloisoleucine elimination rate constant (0.067 h(-1)) was in the normal range (0.069+/-0.012 h(-1), n = 4). In an oral L-[1-13C]leucine load (38 micromol/kg body wt), 19.5% of the tracer dose applied was recovered in exhaled 13CO2 versus 18.9+/-3.6% in healthy subjects (n = 10). Thus, the patient exhibited obviously normal whole-body catabolic rates although branched-chain L amino acid oxidation was confined to the liver transplant. Most likely, the enhanced substrate supply from extrahepatic sources led to an elevation of the plasma concentrations and thus induced a compensatory enhancement of the metabolic flux through the branched-chain 2-oxo acid dehydrogenase complex in the intact liver tissue. PMID- 11196105 TI - Hepatocellular carcinoma despite long-term survival in chronic tyrosinaemia I. AB - Tyrosinaemia I (fumarylacetoacetate hydrolase deficiency) is an autosomal recessive inborn error of tyrosine metabolism that produces liver failure in infancy or a more chronic course of liver disease with cirrhosis, often complicated by hepatocellular carcinoma, in childhood or early adolescence. We studied a 37-year-old woman with tyrosinaemia I whose severe liver disease in infancy and rickets during childhood resolved with dietary therapy. From 14 years of age she resumed an unrestricted diet with the continued presence of the biochemical features of tyrosinaemia, yet maintained normal liver function. In adult years she accumulated only small amounts of succinylacetone. Despite this evolution to a mild biochemical and clinical phenotype, she eventually developed hepatocellular carcinoma. Her fumarylacetoacetate hydrolase genotype consists of a splice mutation, IVS6-1g>t, and a novel missense mutation, Q279R. Studies of resected liver demonstrated the absence of hydrolytic activity and of immunological expression of fumarylacetoacetate hydrolase in liver tumour. In nontumoral areas, however, 53% of normal hydrolytic activity and immunologically present fumarylacetoacetate hydrolase was found. This case demonstrates the high risk of liver cancer in tyrosinaemia I even in a seemingly favourable biological environment. PMID- 11196107 TI - Tyrosine hydroxylase deficiency unresponsive to L-dopa treatment with unusual clinical and biochemical presentation. AB - Tyrosine hydroxylase (TH) deficiency is generally considered as a cause of the autosomal recessive form of dopa-responsive dystonia, also known as Segawa disease. Clinical hallmarks comprise parkinsonian and other extrapyramidal symptoms. Biochemically the defect leads to the defective synthesis of catecholamines, in particular dopamine. The diagnosis relies on a characteristic pattern of biogenic amine metabolites exclusively in the CSF and can be confirmed by establishing a mutation in the TH gene. Here we present a patient meeting all diagnostic criteria, including a new homozygous mutation (926T > C) with confirmed parental heterozygosity, extrapyramidal symptoms, but atypical other symptoms with periodic neurological episodes observed every 4 days and unresponsive to dopa treatment. The CSF biochemical abnormalities were severe. Uncharacteristically, a strongly abnormal urinary catecholamine metabolite pattern was also consistently observed. The atypical presentation of this patient shows that the clinical and metabolic phenotype of TH deficiency is more variable than formerly thought, and that the condition should no longer be considered as a treatable disorder per se. PMID- 11196108 TI - Trifunctional protein deficiency: three families with significant maternal hepatic dysfunction in pregnancy not associated with E474Q mutation. AB - We report five families with trifunctional protein deficiency in which, during pregnancy, three mothers experienced significant hepatic disease when carrying an affected fetus. Diagnoses were based on increased levels of long-chain hydroxyacylcarnitines and deficiencies of 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and 3-ketoacyl-CoA thiolase activity in fibroblasts. All affected infants lacked the common E474Q mutation associated with isolated LCHAD deficiency. This mutation is thought to be a predisposing factor for maternal hepatic disease in pregnancy. Our findings suggest that other defects in this enzyme complex might be responsible for maternal hepatic complications in pregnancy. PMID- 11196109 TI - Plasma creatinine assessment in creatine deficiency: A diagnostic pitfall. AB - Guanidinoacetate methyltransferase (GAMT) deficiency (creatine deficiency syndrome) is a recently discovered inborn error of creatine biosynthesis. Affected patients have elevated concentrations of guanidino-acetate, the metabolic precursor of creatine, in urine, plasma and cerebrospinal fluid. In addition, urinary creatinine excretion and plasma creatinine concentration are decreased. For biochemical evaluation of patients suspected to suffer from GAMT deficiency, correct quantification of creatinine in plasma is important. Here we report our experience with different quantification techniques. We found that creatinine in plasma from two GAMT-deficient patients appeared normal when measured by the Jaffe method but was decreased when measured enzymatically or by HPLC. The apparently normal levels of creatinine as measured by the Jaffe method were not caused by guanidinoacetate. In urine, the Jaffe method and the enzymatic method gave similar results, indicating that in urine no false elevations of creatinine can be expected. As the Jaffe method is still widely used for routine plasma creatinine measurements, it is important to realize it cannot be used to exclude GAMT deficiency. PMID- 11196110 TI - Neuroleptic malignant syndrome in a patient with citrullinaemia. PMID- 11196111 TI - Ornithine carbamoyltransferase deficiency presenting with chorea in a female. PMID- 11196112 TI - Holocarboxylase synthetase deficiency: urinary metabolites masked by gross ketosis. PMID- 11196113 TI - Hyperprolinaemia in patients with deletion (22)(q11.2) syndrome. PMID- 11196114 TI - Prolactin, a marker for cerebral dopamine deficiency in patients suffering from phenylketonuria (PKU)? PMID- 11196115 TI - A novel mutation in the glucose-6-phosphatase gene in Korean twins with glycogen storage disease type Ia. PMID- 11196116 TI - A novel mitochondrial transfer RNA proline mutation. PMID- 11196117 TI - Age-related scattered hypofluorescent spots on late-phase indocyanine green angiograms. AB - PURPOSE: Scattered hypofluorescent spots may be seen on indocyanine green (ICG) angiograms of regions that do not show abnormalities when viewed with an ophthalmoscope. Hypofluorescent spots are found in several pathologic conditions, typically in inflammatory diseases. In this report, we describe hypofluorescent spots in normal fundi and show that such spots can be age-related. METHODS: Video fundus camera ICG angiograms of 115 eyes of 109 patients aged 12 to 85 years with normal fundi or with only age-related maculopathy were reviewed. The relation between age and scattered hypofluorescent spots, and between age-related maculopathy and spots was examined utilising regression analysis. RESULTS: Scattered hypofluorescent spots were seen throughout the posterior pole in 24 eyes of 23 patients and in a portion of the posterior pole in 30 eyes of 29 patients. The hypofluorescent spots were noted between 26 and 37 minutes after dye injection. Patient age ranged from 51 to 80 years, and regression analysis showed that the frequency of hypofluorescent spots increased significantly with aging (p < 0.05). However, age-related maculopathy did not show a significant relation to the spots. CONCLUSION: Scattered hypofluorescent spots seen in the posterior pole during the late-phase of ICG angiograms can apparently be due to aging of the fundus. PMID- 11196118 TI - Parafoveal arteriolar obstruction after ocular trauma in a patient with systemic lupus erithematosus. AB - BACKGROUND: Retinal arterial obstruction after ocular trauma is a rarely described entity which presents a still controversial pathogenesis. However, intravascular leucoembolization in response to activation of complement factor 5 (C5a) has now been hypothesized as a possible cause of arterial embolization after severe trauma. Coincidentally, the pathogenesis of vascular lesions seen in active systemic lupus erithematosus is also related to the activation of the same complement factor. METHODS: We present the case of a 32-year-old man with active systemic lupus erithematosus who received a blunt trauma in his right eye and immediate developed severe visual loss. RESULTS: Ophthalmoscopy of the affected eye revealed a cherry-red spot macula, small hemorrhages and edema of the posterior pole. Fluorescein-angiography showed obstructions and staining of small branches of arterioles in the parafoveal region. After 2 months of follow-up, the ophthalmoscopic picture evolved to optic atrophy and the visual acuity remained severely reduced. CONCLUSION: We hypothesize that patients with complement mediated diseases are predisposed to retinal arteriolar obstruction after ocular trauma. PMID- 11196119 TI - Late Horner's syndrome following the bite of a black widow spider. AB - In this paper, we report on the case of a 23-year-old man who presented with a ptosis of the right upper lid and a miosis 1 month after being bitten in his right hand by Latrodectus revivenis. A positive cocaine test confirmed a diagnosis of Homer's syndrome. PMID- 11196120 TI - The antibacterial effect of topical anesthetic proparacaine on conjunctival flora. AB - PURPOSE: To investigate the antibacterial effect of topical anesthetic proparacaine on conjunctival flora. METHODS: One hundred and forty-four eyes of 72 patients awaiting cataract surgery were included in the study. A commercially available solution of proparacaine, preserved with benzalkonium chloride 0.01%, was instilled in one eye of all subjects while the vehicle solution, including the same concentration of preservative in aqueous solution, was administered to the other eye. Conjunctival cultures were taken from all eyes before and 15 minutes after the instillation of proparacaine and the vehicle. RESULTS: Of the 144 eyes, 76 (52.8%) had positive-conjunctival cultures with the most commonly isolated organisms being coagulase-negative staphylococci in each group. Of the 76 culture-positive eyes, 40 (52.6%) received proparacaine and 36 (47.4%) the vehicle preparation. Fifteen minutes after the instillation of proparacaine and the vehicle eyedrops, four eyes (10%) and 12 eyes (33.3%) had culture-positive conjunctival smears, respectively. Proparacaine significantly reduced the number of culture-positive eyes (p = 0.0003), in contrast to the vehicle (p = 0.21). CONCLUSION: A topical anesthetic, proparacaine, demonstrates antibacterial effects on the conjunctival flora. PMID- 11196121 TI - Evolution of ocular clinical and electrophysiological findings in pediatric Bardet-Biedl syndrome. AB - Bardet-Biedl syndrome (BBS) is a hereditary autosomal-recessive disorder, characterized by mental retardation, obesity, pigmentary retinopathy, polydactyly and, only in males, hypogenitalism. Even though genetic studies have revealed five different forms of BBS correlated to distinct loci on different chromosomes, a diagnosis of BBS is still primarily based on clinical data. The present study discusses the evolution of clinical ophthalmological and electrophysiological characteristics of BBS patients in developmental age. The main results obtained on a sample of 13 pediatric patients are the following: * progressive loss of visual acuity arised early in the first decade of life * ophthalmoscopic signs of pigmentary retinopathy were present only in 46% of the children studied * striking anomalies in the electroretinogram were also detected in the cases without pigmentary retinopathy * the electroretinographic results, when detectable, suggested a greater involvement of the photopic system as against the scotopic system. PMID- 11196122 TI - A comparative study on the effects of apraclonidine and timolol on the ophthalmic blood flow velocity waveforms. AB - PURPOSE: To evaluate the effects of topical timolol and apraclonidine on retrobulbar blood flow velocity waveforms in a group of healthy volunteers. METHODS: Apraclonidine 1% and timolol maleate 0.5% single dose administrations were crossed over double masked in 12 healthy volunteers. The intraocular pressure measurements were followed by Doppler examination of the ophthalmic artery and the central retinal artery. RESULTS: Intraocular pressure was reduced significantly on both treated and fellow eyes after timolol (p = 0.003, p = 0.04 respectively) and after apraclonidine (p = 0.002, p = 0.01 respectively). After apraclonidine administration end diastolic velocity, mean velocity decreased and pulsatility index increased in the ophthalmic artery of both treated and fellow eyes. Resistivity index increased and peak systolic velocity decreased only in the ophthalmic artery of treated eyes. All Doppler indices remained nonsignificant for central retinal artery of both eyes. After timolol administration there were no significant changes of the Doppler indices in the ophthalmic artery and central retinal artery of the treated and fellow eyes. CONCLUSION: Topical timolol and apraclonidine significantly reduced the intraocular pressure. Single dose administration of apraclonidine 1% increased the vascular impedance distal to the ophthalmic artery. On the other hand, timolol 0.5% had no effect on vascular impedance. PMID- 11196123 TI - Pseudoexfoliation and glaucoma in eyes with retinal vein occlusion. AB - PURPOSE: To evaluate pseudoexfoliation (PE) and pre-existent glaucoma in eyes with branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO). METHODS: Consecutive eyes with a diagnosis of BRVO (73 eyes of 70 patients) and CRVO (53 eyes of 49 patients) examined between July and December 1998 comprised the study eyes. Age-matched control group consisted of 384 eyes of 192 outpatients. The prevalence of PE and glaucoma were determined and appropriate statistical tests were performed. RESULTS: PE was present in six of 73 eyes with BRVO (8.2%), 11 of 53 eyes with CRVO (20.8%) and 20 of 384 control eyes (5.2%). Two of 73 eyes with BRVO (2.7%) and 10 of 53 eyes with CRVO (18.9%) had glaucoma. Compared with the control eyes, PE was significantly more common in eyes with CRVO and coexistent glaucoma was significantly more common both in eyes with CRVO and in eyes with BRVO. CONCLUSION: While glaucoma seems to be a risk factor both for BRVO and CRVO, PE is a likely risk factor for CRVO. PMID- 11196124 TI - Effect of oral felodipine on ocular circulation. AB - PURPOSE: To evaluate the effects of felodipine, a calcium channel blocker, on ocular circulation. METHODS: In a double blind, randomized, crossover design, 10 volunteers received placebo or felodipine on 2 separate days. Bidirectional laser Doppler velocimetry (BLDV), laser Doppler flowmetry (LDF), and monochromatic fundus photography (MFP) were employed to assess retinal, choroidal, and optic nerve rim circulatory parameters. Measurements were obtained at baseline, 1.5, and 3 hours after dosing. Blood pressure, intraocular pressure (IOP), and heart rate were monitored, and perfusion pressure (PP) was calculated. RESULTS: In comparison to placebo, significant average percentage decreases in diastolic blood pressure (BPd; p = 0.001), mean blood pressure (BPm; p = 0.003), and perfusion pressure (PP; p = 0.003) were observed 1.5 hours following felodipine. No significant differences were observed following placebo. Retinal, choroidal and optic nerve rim circulatory parameters showed no significant changes after placebo or felodipine. A significant positive correlation between BPd and optic nerve velocity (ONve1) was observed 3 hours following felodipine (R = +0.654; p = 0.040). In contrast, no significant correlation between BPd and ONve1 was noted (R = +0.198; p = 0.583) following placebo. CONCLUSIONS: No significant change in retinal, optic nerve rim, or foveolar choroidal blood flow were observed, a factor that may be important in the treatment of systemic hypertension in patients with glaucoma. PMID- 11196125 TI - Visual recovery in unilateral traumatic pediatric cataracts treated with posterior chamber intraocular lens and anterior vitrectomy in Pakistan. AB - PURPOSE: To evaluate visual recovery in unilateral traumatic cataracts in children treated with posterior chamber intraocular lens implantation and anterior vitrectomy. METHODS: Sixteen children with unilateral traumatic cataract between ages 3-10 years (mean, 5 years 8 months) were treated with posterior chamber intraocular lens implantation and anterior vitrectomy. Surgery was performed between 2 weeks and 7 months (mean, 7.75 weeks) after injury. Follow up was between 9 and 29 months (mean, 17.9 months). RESULTS: The most common postoperative complication was fibrinous uveitis, which developed in 4 children (25%). All eyes had a clear visual axis postoperatively; none required capsulotomy. The mean postoperative refraction was +0.9 diopters (range, +3.50 to -2.75 diopters). Three eyes (18.75%) had visual acuity of 6/9, 8 eyes (50%) had visual acuity of 6/12 or better, and 11 eyes (68.75%) had visual acuity of 6/18 or better. The cause of poor visual acuity was cystoid macular edema in one eye, macular scars in two eyes, and amblyopia in one eye. CONCLUSIONS: Unilateral traumatic cataracts in children in whom aphakia is corrected with posterior chamber lens implantation combined with anterior vitrectomy result in good visual outcome, and we recommend this treatment modality in traumatic cataract in children. PMID- 11196126 TI - The effect of latanoprost on aqueous humor PGF2alpha levels in glaucoma patients. AB - AIM: The purpose of this study is to evaluate the effect of the PGF2alpha isopropyl ester analogue, Latanoprost which is a new ocular hypotensive topical agent, on the aqueous humor PGF2alpha levels in open-angle glaucoma patients. METHODS: Patients diagnosed with either capsular or primary open-angle glaucoma and scheduled for trabeculectomy, were consecutively enrolled in the study. Group 1 represented the control group (n = 17) and Group 2 represented the Latanoprost treatment group (n = 9). All the topical drugs were stopped 10 days preoperatively and only systemic carbonic anhydrase inhibitors were continued if necessary. Group 2 patients received topical 0.005% Latanoprost once daily for 5 10 days preoperatively. During trabeculectomy operation, aqueous samples were taken through paracentesis from the patients. Aqueous humor levels of PGF2alpha and its metabolite 13,14-dihydro-15-keto-PGF2alpha were measured using enzyme immunoassay. RESULTS: The mean PGF2alpha levels were 24.38 +/- 5.79 pg/ml in the control group and 10.99 +/- 4.11 pg/ml in the Latanoprost group, the difference of which was statistically significant (p < 0.05). In the Latanoprost group, there was a positive correlation between levels of PGF2alpha, and its metabolite (p < 0.05). CONCLUSION: Pretreatment with PGF2alpha isopropyl ester analogue, Latanoprost topically decreased PGF2alpha levels in the aqueous humor of glaucomatous eyes, probably due to its uveoscleral outflow increasing effect. The clinical importance and application of this result has to be determined. PMID- 11196127 TI - 360 Degrees of epibulbar granulation tissue thirteen years after silicone circle buckle operation. AB - To demonstrate a granulomatous reaction to silicone buckel thirteen years after retinal detachment surgery. We report on a 71-year-old man who developed a 360 degrees of epibulbar granulation tissue due to silicone circle buckel. The granulation tissue was demonstrated by a computer tomography and histologically. A granulomatous reaction to silicone circle buckel can be found many years from the first operation. Biopsy is always necessary to establish a definitive diagnosis. Treatment of 360 degrees of epibulbar granulation tissue causing ocular dysfunction is by surgical excision. PMID- 11196128 TI - Correlation between high-pass resolution perimetry and standard threshold perimetry in subjects with glaucoma and ocular hypertension. AB - PURPOSE: To evaluate the correlation between High-Pass Resolution Perimetry (HRP) and standard threshold perimetry in patients with glaucoma or ocular hypertension. METHODS: 31 glaucomatous patients and 37 ocular hypertension subjects with previous perimetric examination experience were consecutively recruited and only one eye for each patient was selected at random. Glaucomatous patients were classified as having primary open angle glaucoma when they had an abnormal visual field and/or an abnormal optic nerve head (ONH)/retinal nerve fiber layer (RNFL) typical of glaucoma, open angle at gonioscopy and no clinically apparent secondary cause for their glaucoma. Ocular hypertension subjects were defined as having intraocular pressure >21 mm Hg on no treatment, normal visual field, normal ONH and RNFL, elevated intraocular pressure without any treatment. All the subjects were examined with Humphrey Field Analyzer (HFA) 640, 'program central 30-2' (Humphrey Systems, San Leandro, CA, USA) and with High-Pass Resolution Perimeter (HRP), Ophthimus version 2.4,'ring program' (Nikon HighTech Vision, Goteborg, Sweden). Visual field indices were obtained with both systems: for HFA mean deviation (MD), corrected pattern standard deviation (CPSD) and short term fluctuation (SF), while for HRP global deviation (GD), local deviation (LD), form index (FI) and neural capacity (NC). The data were analyzed by descriptive analysis, Student's t test with Bonferroni's correction or Mann Whitney non-parametric test and Pearson or Spearman's correlation coefficient. RESULTS: A significant correlation was found between MD and GD (r = -0.81), CPSD and LD (r = 0.87), PSD and LD (r = 0.72). NC was significantly correlated with MD (r = 0.76), GD (r = -0.94). FI was significantly correlated with PSD (r = -0.58), CPSD (r = -0.72), LD (r = -0.56). When the same data were analyzed for the glaucomatous group only, similar results were found; in the ocular hypertensive group no significant correlation was found except between NC and MD (r = 0.52). CONCLUSION: HRP indices vary comparably with HFA indices. Parameters as NC and FI were significantly correlated with standard visual field indices of both HFA and HRP. Although the clinical applications for FI are not clear yet, NC could detect both early glaucomatous damage and age related changes. PMID- 11196129 TI - Cytogenetics of donkey chromosomes: nomenclature proposal based on GTG-banded chromosomes and depiction of NORs and telomeric sites. AB - With the expansion of comparative genome analysis across different mammals, there is an increasing need to have well-defined banded karyotypes for the species chosen for investigation. In this context, the steadily growing gene mapping data in the donkey urgently require a framework whereby alignment/comparison of genetic information can be readily made with equids and other mammalian species. Hence a GTG-banded karyotype of the donkey (Equus asinus; EAS) is presented, along with schematic drawings and nomenclature of the banded chromosomes. In addition, the most characteristic features of individual chromosomes are described and their relative size estimated. Using the FISH approach, the location of nucleolous organizer regions (NORs) and telomeric repeat sequences (TTAGGG) were detected. Where possible, information on asine chromosomes is supplemented with known/likely equine and human homologues. The study thus primarily aims to provide an appropriate cytogenetic basis for the donkey chromosomes, so that research focused on gene mapping and comparative genomics in this species can be reported under a common format. PMID- 11196130 TI - Meiotic metaphase I pairing behavior of a 5BL recombinant isochromosome in wheat. AB - A recombinant isochromosome i5BLrec of wheat was developed with one arm and the proximal 36% of the other arm of Chinese Spring (CS) origin and the distal 64% of the recombined arm of Triticum turgiduM subsp. dicoccoides origin. The i5BLrec provides an unusual opportunity to analyze the role of the centromere or arm heterozygosity in chromosome prealignment and synapsis during meiosis. In monosomic condition, the i5BLrec formed a ring univalent in 86.8% of the pollen mother cells (PMCs) at meiotic metaphase I. In the disomic condition, the two i5BLrec preferentially paired as a normal bivalent in 74.8% of the PMCs, which differed significantly (p <0.01) from the normal bivalent pairing of 51% observed in diisosomic 5BL chromosomes of the CS (Di5BL(CS)) control plants. In plants with one i5BLrec and a normal 5B(CS), the long arm of 5B(CS) paired with the homologous arm of i5BLrec in 54.4% of the PMCs, and 40.4% of the PMCs had a 5B(CS) univalent and a i5BLrec ring univalent. The implications of the i5BLrec pairing data on the mechanism of Ph1 gene action are discussed. PMID- 11196131 TI - Analysis of replication timing at the FRA10B and FRA16B fragile site loci. AB - The molecular basis for the cytogenetic appearance of chromosomal fragile sites is not yet understood. Late replication and further delay of replication at fragile sites expressing alleles has been observed for FRAXA, FRAXE and FRA3B fragile site loci. We analysed the timing of replication at the FRA10B and FRA16B loci to determine whether late replication is a feature which is shared by all fragile sites and, therefore, is a necessary condition for chromosomal fragile site expression. The FRA10B locus was located in a transitional region between early and late zones of replication. Fragile and non-fragile alleles exhibit a similar replication pattern proximal to the repeat but fragile alleles are delayed relative to non-fragile ones on the distal side. Although fragility at FRA10B appears to be caused by expansion of an AT-rich repeat in the region, replication time near the repeat was similar in fragile and non-fragile alleles. The FRA16B locus was late replicating and appeared to replicate even later on fragile chromosomes. While these observations are compatible with the hypothesis that delayed replication may play a role in fragile site expression, they suggest that replication delay may not need to occur at the expanded repeat region itself in order to be permissive for fragility. PMID- 11196132 TI - Robertsonian polymorphism, B chromosomes variation and sex chromosomes heteromorphism in the african water rat Dasymys (Rodentia, Muridae). AB - Chromosome banding analysis (G- and C-bands) of Dasymys rufulus from Senegal, Mali and the Ivory Coast, and D. cf. incomtus from Eastern and South-western Ethiopia was carried out. The diploid numbers (2N) in the former species range between 36 and 39 due to the presence of 0-3 small biarmed heterochromatic B chromosomes, resulting in a corresponding variation of the number of autosomal arms (NFa) between 44 and 50. The basic autosomal set was, however, constant and identical in these specimens. The karyotypes of D. cf. incomtus from Eastern and Western Ethiopia were found to be different (2N = 40 and 38, respectively). Comparison of G-banding patterns of the species studied revealed that they differ from each others by 1-2 Rb fusions/fissions, one paracentric inversion and heteromorphous sex chromosomes resulting from addition/deletion of heterochromatic blocks (X) and pericentric inversion (Y). In the light of the available chromosome banding data, the significance of intraspecies karyotypic variability within D. cf. incomtus and its relevance to the systematics of the genus are discussed. PMID- 11196133 TI - The human autoantigen MCP1 is required during early stages of DNA replication. AB - Metaphase chromosome protein 1 (MCP1) is a nuclear autoantigen that is associated with condensed chromosomes throughout mitosis. During interphase, this antigen shows a speckle distribution in the nucleus, excluding the nucleolus. Additionally, MCP1 binds tightly to the scaffold/matrix component of nuclei and isolated chromosomes. In order to determine the in-vivo localization of the antigen, we have expressed MCP1 fused to EGFP in tissue culture cells. The results demonstrate that MCP1 is located in the nucleus during interphase and during mitosis associates tightly to condensed chromosomes. Furthermore, microinjection of specific antibody confirms these results. We have used a specific monoclonal antibody (mAb 402) against MCP1 to assess the function of this antigen during cell cycle progression. HeLa and Ptk-2 cells that were microinjected into the nucleus and/or cytoplasm at G1/S and very early S phase were not able to progress and complete DNA replication. However, injection of mAb 402 at mid or late S phase does not prevent completion of DNA replication and subsequent progression into mitosis. Microinjection of mAb 402 in Ptk-2 cells synchronized in mitosis did not interfere with progression of mitosis and cells divided. Our results suggest that MCP1 is required at the G1/S transition and during early S phase. PMID- 11196134 TI - Stability of transferred human chromosome fragments in cultured cells and in mice. AB - Chromosome fragments represent feasible gene delivery vectors with the use of microcell-mediated chromosome transfer. To test a prerequisite for a gene delivery vector, we examined the stability of human chromosome fragments (hCFs) in cultured cells and in trans-chromosomic (Tc) mice. Fragments of human chromosomes 2 (hCF(2-W23)), 11 (hCF-11) and 14 (hCF(SC20)) tagged with neo were introduced into the TT2F mouse ES cells, and retention of the hCFs was examined by FISH during long-term culture without selection. In contrast to the gradual loss of hCF(2-W23) and hCF-11, hCF(SC20) remained stable over 70 population doublings in the ES cells. The hCF(SC20) was also stable in cultured human tumor cells and chicken DT40 cells. We have previously generated chimeric mice using the ES cells harboring the hCF(2-W23) or hCF(SC20), followed by production of Tc mice. Although both the hCF(2-W23) and hCF(SC20) persisted in cells of Tc mice as an additional chromosome and were transmitted to offspring, the hCF(SC20) was more stable than the hCF(2-W23) in F1 and F2 mice. The present study shows that the stability of hCFs in Tc mice differs with tissue types and with genetic background used for successive breedings. Thus, the hCF(SC20), which was relatively stable in both mouse and human cells, may be a promising candidate for development as a gene delivery vector. PMID- 11196135 TI - Comparative FISH mapping of the ancestral fusion point of human chromosome 2. AB - It is known that human chromosome 2 originated from the fusion of two ancestral primate chromosomes. This has been confirmed by chromosome banding and fluorescence in-situ hybridization (FISH) with human chromosome-2-specific DNA libraries. In this study, the order of 38 cosmid clones derived from the human chromosome region 2q12-q14 was exactly determined by high-resolution FISH in human chromosome 2 and its homologous chromosomes in chimpanzees (Pan trogrodydes, 2n=48) and cynomolgus monkeys (Macacafascicularis, 2n = 42). This region includes the telomere-to-telomere fusion point of two ancestral ape-type chromosomes. As a result of comparative mapping, human chromosome region 2q12-q14 was found to correspond to the short arms of chimpanzee chromosomes 12 and 13 and cynomolgus monkey chromosomes 9 and 15. It is noted that no difference was detected in the relative order of the cosmid clones between human and chimpanzee chromosomes. This suggests that two ancestral ape-type chromosomes fused tandemly at telomeres to form human chromosome 2, and the genomic organization of this region is thought to be considerably conserved. In the cynomolgus monkey, however, the order of clones in each homologue was inverted. In addition to cosmid mapping, two chromosome-2-specific yeast artificial chromosome (YAC) clones containing the fusion point were identified by FISH. PMID- 11196136 TI - Gene density in the Giemsa bands of human chromosomes. AB - The human genome is formed by isochores belonging to five families, L1, L2, H1, H2 and H3, that are characterized by increasing GC levels and gene concentrations. In-situ hybridization of DNA from different isochore families provides, therefore, information not only on the correlation between isochores and chromosomal bands, but also on the distribution of genes in chromosomes. Three subsets of R(everse) bands were identified: H3+, H3* and H3-, that contain large, moderate, and no detectable amounts, respectively, of the gene-richest H2 and H3 isochores, and replicate very early and early, respectively, in S phase of the cell cycle. Here, we investigated the GC levels, replication timings and DNA compaction of G(iemsa) bands. We showed that G bands comprise two different subsets of bands, one of which is predominantly composed of L1 isochores, replicates at the end of the S phase, has a higher DNA compaction relative to H3+ bands and corresponds to the darkest G bands of Francke (1994). In contrast, the other subset is composed of L2 and H1 isochores, has less-extreme properties in replication and composition and corresponds to the less-dark G bands of Francke. PMID- 11196137 TI - Chromosome mapping of GABRB3 and PML loci in macaca and cercopithecus indicates the mechanism of evolution of human chromosome 15. PMID- 11196138 TI - [Dental agenesis. Results of a prospective study of 30 cases]. AB - OBJECTIVE: We conducted a prospective study to determine the types of bone anomalies observed in different types of dental agenesia. PATIENTS AND METHOD: This prospective series included 30 patients who attended our pluridisciplinary clinic since 1988. There were 22 cases of non syndromal agenesia and 8 cases of syndromal agenesia. Patients consulted for a variety of reasons, no specific sign was found. The diagnosis was based on the panoramic x-ray and confirmed at the genetic consultation. RESULTS: Results were systemized by localization of the agenesia. In all cases, the height of the bone crest was preserved compared with the adjacent teeth. In the anterior part of the maxillary, the bone crest was thin showing a water drop aspect. In the posterior maxillary, there was a decrease in the subsinusal height due to invagination of the floor of the sinus. In the anterior part of the mandible, the crest had a knife blade aspect but no loss of height and in the posterior part, a preserved distance between the residual crest rim and the dental canal. DISCUSSION: In 60% of the solitary agenesias in the anterior part of the maxillary, augmentation was not required. A sinus graft was required in all cases involving the posterior maxillary. Multiple anterior or lateral agenesias were treated with a parietal graft. PMID- 11196139 TI - [Maxillary distraction and implantology]. AB - Vertical alveolar distraction can be a useful surgical technique in preprosthetic reconstructive surgery, especially after failed autogenous onlay bone grafting. The main advantage of this technique is to allow expansion of both the bone and soft tissue. Through a case of vertical alveolar reconstruction by distraction osteogenesis and implant rehabilitation in a patient who had undergone two previously unsuccessful interposition bone graft procedures, this report illustrate the advantages of alveolar ridge augmentation by distraction osteogenesis. PMID- 11196140 TI - [Mandibular atrophy and a screw-retained implant-supported prosthesis]. AB - Prosthetic care for mandibular atrophy has raised many difficult problems, particularly in the most severe cases. The solution to most of these problems lies in the use of osteointegrated implants. Good results were obtained by using a small number of implants associated with adjustable overdenture prostheses or, alternatively, by using a larger number of implants (5 or 6) associated with a screw fixed prosthesis with posterior cantilever. Cantilever prostheses can provide support for the mental foramen zones and the posterior zones of the mandibular body where bone resorption is important after application of adjustable plates to the fibromucosa. PMID- 11196141 TI - [Evaluation of mandibular propulsion appliances in children. A study of 18 cases]. AB - PURPOSE: Mandibular propulsion appliances are used currently in the treatment of class II malocclusion. The purpose of this study was to evaluate their effects on facial development to formulate specific indications. PATIENTS AND METHODS: Eighteen children (mean age 9-12) treated with a propulsion device for a class II division 1 malocclusion with a minimum of 4 mm overjet were included in a retrospective study over a 4 year period. We compared maxillomandibular and dentoalveolar position before and after treatment using Delaire computer software cephalometric analysis and superpositions. RESULTS: Statistically significant effects on molar discrepancy (p = 0.0002), overjet (p = 0.0003), sagittal mandibular position (p = 0.0040 for FM-Me/theoretical and p = 0.0010 for NP-FM Me), mandibular length (p = 0.004 for FM-Me/theoretical), mandibular corpus length (p = 0.0286 for Go-Me/theoretical), upper incisors palatal version (p = 0.0002), and on lower incisors lip version (p = 0.0436) were assessed. No action on maxillary growth (p = 0.7274 for FM-NP/theoretical), ramus length (p = 0.9651 for Cp-Go/theoritecal), lower facial height (p = 0.7045 for ENA-Me/theoretical) or translation of the alveolar arches (p = 0.9571 for A-Pti'/ENA-Pti and p = 0.1564 for B-Pa'/B-Pa) could be confirmed. CONCLUSIONS: An increase in mandibular corpus development and no effect on alveolar arches suggests a basal mandibular action for this device. This concludes that retromandibular position and brachycorpus with upper incisor lip version, without lower incisors lip version are the best indications for mandibular propulsion appliances. Prospective studies should be carried out to confirm this hypothesis. PMID- 11196142 TI - [Indications and implications of surgical maxillary expansion in orthodontic surgery]. AB - Surgically assisted rapid maxillary expansion is an accepted method for correction of transverse skeletal and dental discrepancies. The surgical technique includes a Lefort I osteotomy with medial palatine osteotomy. The maxillary must be totally released to achieve the desired expansion. There are several advantages: bone apposition in osteotomy sites, reduced risk of dental version or extrusion compared with orthopedic care, secondary surgical cure of complex dysmorphism requiring fewer segmentary osteotomies. Finally, we examined skeletal side effects induced by surgically assisted rapid maxillary expansion in the vertical and sagittal dimension of the face. PMID- 11196143 TI - [Peroperative use of a silicone occlusal block for palatal and lingual support in orthognathic surgery]. AB - We present an alternative to acrylic occlusal wafers in orthognatic surgery. We propose using a silicone wafer that is easier to position preoperatively. PMID- 11196144 TI - [Success and failure in orthodontic maxillofacial treatment with superelastic shape-memory nickel-titanium wires. Apropos of 4 examples]. AB - We present four clinical cases to show the usefulness of superelastic shape memory NiTi alloy wires in orthodontics. Martensitic and austenitic states of the alloy facilitate wire insertion in the bracket slot, creating a gently continuous force to move the tooth whatever the deformation of the wire. Use of a more physiological force lessens the risk of therapeutic errors due to misevaluated dysfunction and/or underlying dysmorphism. PMID- 11196145 TI - [Semi-rigid bracket splinting of teeth after traumatic luxation]. AB - We describe a non-rigid procedure using brackets for splinting teeth after traumatic avulsion. This type of appliance preserves alveolodental ligament physiology and enables immediate mastication without occlusal obstruction. Installation is easy, except when severe bleeding or alveolar fracture occurs. PMID- 11196146 TI - Protection against 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine cytotoxicity and DNA adduct formation in human prostate by glutathione S transferase P1. AB - The prostate has been identified as a target for 2-amino-1-methyl-6 phenylimidazo[4,5-b]pyridine (PhIP)-induced carcinogenesis. Humans are exposed to PhIP through ingestion of well-done cooked meats, and there is evidence from epidemiological studies that implicates red meat consumption in prostate carcinogenesis. The alpha and pi class isoforms of glutathione S-transferases (GSTs) have been shown to inhibit adduction of activated PhIP metabolites to DNA in cell-free systems. In humans, silencing of GST pi(GSTP1) through CpG island hypermethylation is found in nearly all prostate carcinomas and is believed to be an early event in prostate carcinogenesis. We hypothesized that suppressed GSTP1 expression in prostate cells would increase their vulnerability to cytotoxicity and DNA adduct formation mediated by activated PhIP metabolites. To test this hypothesis, the human prostate adenocarcinoma cell line, LNCaP, which contains a silenced GSTP1 gene, was genetically modified to constitutively express high levels of GSTP1. Both LNCaP and LNCaP-GSTP1 cells exposed to N-OH-PhIP, but not parent PhIP, for 24 h showed a dose-dependent decrease in cell viability. GSTP1 overexpressing cells had LC50s 30-40% higher than cells transfected with the vector alone. PhIP-DNA adducts isolated from LNCaP-derived cells and primary human prostate tissue cultures exposed to N-OH-PhIP were analyzed by liquid chromatography/electrospray ionization mass spectrometry. Primary cultures of human prostate tissue and LNCaP-GSTP1 cells had approximately 50% lower adduct levels than parental LNCaP and vector control cells. Bioactivation assays using LNCaP cytosols showed that enzymatic activation of N-OH-PhIP to a DNA binding species was dependent on ATP and could be inhibited by recombinant human GSTP1 in the presence of glutathione. This evidence confirms that N-OH-PhIP can be bioactivated to a DNA binding species in human prostate and human prostate derived cells. These observations provide the basis for using LNCaP and LNCaP GSTP1 cells as a model system for studying the role of this enzyme in protection against N-OH-PhIP induced DNA damage in prostate carcinogenesis. Loss of GSTP1 expression in human prostate may, therefore, enhance its susceptibility to carcinogenic insult by compounds such as N-OH-PhIP. Conversely, induction of GSTs in early-stage prostate carcinogenesis may be a useful protective strategy. PMID- 11196147 TI - Synthesis and evaluation of 18F-labeled choline as an oncologic tracer for positron emission tomography: initial findings in prostate cancer. AB - The up-regulation of rates of choline uptake and phosphorylation in certain malignancies has motivated the development of positron-labeled choline analogues for noninvasive detection of cancer using positron emission tomography (PET). The choline analogue, no-carrier-added [18F]fluoromethyl-dimethyl-2-hydroxyethyl ammonium (FCH), was synthesized through the intermediate [18F]fluorobromomethane. FCH was evaluated in relationship to 2-[18F]fluoro-2-deoxyglucose (FDG) as an oncological probe in cultured PC-3 human prostate cancer cells, a murine PC-3 human prostate cancer xenograft model, and in PET imaging studies of patients with prostate cancer. FCH was synthesized in 20-40% radiochemical yield and >98% radiochemical purity. Accumulation of FCH and FDG were comparable in cultured prostate cancer cells, whereas only FCH was inhibited (90%) by hemicholinium-3, a specific inhibitor of choline transport and phosphorylation. FCH showed similar biodistribution to [14C]choline in the tumor-bearing mouse, with prominent renal and hepatic uptake. Tumor uptake of FCH was similar to choline and FDG in the mouse model, although tumor:blood ratios were moderately higher for FCH. Initial PET imaging studies in prostate cancer patients showed high uptake of FCH in advanced prostate carcinoma and detection of osseous and soft tissue metastases. FCH uptake by tumors was markedly reduced in patients rescanned during androgen deprivation therapy. It is concluded that FCH closely mimics choline uptake by normal tissues and prostate cancer neoplasms. FCH is potentially useful as a PET tracer for detection and localization of prostate cancer and monitoring effects of therapy. PMID- 11196148 TI - (+)-Catechin inhibits intestinal tumor formation and suppresses focal adhesion kinase activation in the min/+ mouse. AB - Colorectal cancer is sensitive to dietary influences. Epidemiological data linking high intake of fruits and vegetables to decreased cancer risk have prompted the search for specific plant constituents implicated in tumor prevention. This task is difficult because of the complex chemical composition of plant foods and the multifactorial nature of carcinogenesis. Researchers are aided in this effort by the C57BL/6J-Min/+ (Min/+) mouse, an animal bearing a germline defect in Apc that is similar to the initiating genetic event in the majority of human colorectal cancers. In this study, we treated Min/+ mice with (+)-catechin, a phenolic antioxidant abundant in certain fruits. Administration of (+)-catechin in an AIN-76A diet at doses of 0.1 and 1% decreased the intestinal tumor number by 75 and 71%, respectively. Mechanistic studies linked this effect to (+)-catechin-induced changes in integrin-mediated intestinal cell survival signaling, including structural alteration of the actin cytoskeleton and decreased focal adhesion kinase (FAK) tyrosine phosphorylation. Immunoblot analysis of small intestine scrapings from Min/+ mice and Apc+/+ wild-type C57BL/6J littermates together with excised Min/+ adenomas showed increased expression of phosphorylated FAK in the macroscopically normal enterocytes of untreated Min/+ mice and adenomas. Confirming the relevance of this signaling pathway, treatment of Min/+ mice with (+)-catechin reduced the expression of phosphorylated FAK to a level similar to the wild-type littermate controls. Thus, the natural abundance and favorable bioavailability of (+)-catechin make it a promising addition to the list of potential colorectal cancer chemopreventive agents. PMID- 11196149 TI - Estrogens reduce and withdrawal of estrogens increase risk of microsatellite instability-positive colon cancer. AB - There are sex differences in the occurrence of microsatellite instability (MSI) in colon tumors. Taken together with the epidemiological evidence that hormone replacement therapy (HRT) and, less consistently, parity, are inversely associated with colon cancer, it has been hypothesized that estrogens are associated with MSI. The purpose of this study was to evaluate sex-specific differences in the prevalence of MSI in colon tumors and to determine whether reproductive history and hormonal exposures are associated with MSI. Using data from a population-based case-control study of 1836 cases with MSI data and 2410 population-based controls, we evaluated sex, reproductive factors, and hormone exposure in relation to the presence or absence of MSI in tumors. MSI was evaluated by a panel of 10 tetranucleotide repeats, the noncoding mononucleotide repeat BAT-26, and the coding mononucleotide repeat in transforming growth factor beta receptor type II (TGFbetaRII). Exposure data on reproduction, hormone use, obesity, and physical activity were obtained from an interviewer-administered questionnaire. Women were less likely then men to have MSI+ tumors at a young age and more likely to have unstable tumors at an older age; we observed a significant interaction (P < 0.01) between age, sex, and MSI. Evaluation of reproductive factors showed that women who had ever been pregnant had half the risk of MSI+ tumors compared with women who had never been pregnant. In complementary fashion, total ovulatory months were associated with an increased risk of MSI+ tumors [odds ratio (OR), 2.1; 95% confidence interval (CI), 1.1-4.0 comparing MSI+ versus MSI- tumors]. Age at first and last pregnancy did not influence the association. The observed associations were strongest among women <60 years of age at the time of diagnosis. Having used oral contraceptives was associated with a lower risk of MSI+ tumors (OR, 0.7; 95% CI, 0.4-1.2); recent users of HRT were at a reduced risk of MSI+ tumors (OR, 0.8; 95% CI, 0.5-1.4); and women who were former HRT users were at an increased risk of MSI+ tumors (OR, 1.8; 95% CI, 1.1-3.0). Obesity and lack of physical activity were associated with an elevated risk of both MSI+ (OR, 1.7; 95% CI, 0.7-3.3) and MSI- (OR, 2.2; 95% CI, 1.7-3.) tumors in men, but only with MSI- (OR, 1.5; 95% CI, 1.1-2.2) tumors in women. The excess of MSI+ tumors in women is explained by the excess of MSI+ tumors at older ages. Our data suggest that estrogen exposure in women protects against MSI, whereas the lack of estrogen in older women increases risk of instability. HRT in these older women may, again, reduce the risk of unstable tumors. A model for the way in which estrogens (endogenous, exogenous, and obesity-associated) modify the risk of MSI+ tumors is proposed. PMID- 11196150 TI - Characterization of the antitumor effects of the selective farnesyl protein transferase inhibitor R115777 in vivo and in vitro. AB - R115777 [(B)-6-[amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)-methyl]-4-(3 chlorophenyl)-1-methyl-2(1H)-quinolinone] is a potent and selective inhibitor of farnesyl protein transferase with significant antitumor effects in vivo subsequent to oral administration in mice. In vitro, using isolated human farnesyl protein transferase, R115777 competitively inhibited the farnesylation of lamin B and K-RasB peptide substrates, with IC50s of 0.86 nM and 7.9 nM, respectively. In a panel of 53 human tumor cell lines tested for growth inhibition, approximately 75% were found to be sensitive to R115777. The majority of sensitive cell lines had a wild-type ras gene. Tumor cell lines bearing H-ras or N-ras mutations were among the most sensitive of the cell lines tested, with responses observed at nanomolar concentrations of R115777. Tumor cell lines bearing mutant K-ras genes required higher concentrations for inhibition of cell growth, with 50% of the cell lines resistant to R115777 up to concentrations of 500 nM. Inhibition of H-Ras, N-Ras, and lamin B protein processing was observed at concentrations of R115777 that inhibited cell proliferation. However, inhibition of K-RasB protein-processing could not be detected. Oral administration b.i.d. of R115777 to nude mice bearing s.c. tumors at doses ranging from 6.25-100 mg/kg inhibited the growth of tumors bearing mutant H-ras, mutant K-ras, and wild-type ras genes. Histological evaluations revealed heterogeneity in tumor responses to R115777. In LoVo human colon tumors, treatment with R115777 produced a prominent antiangiogenic response. In CAPAN-2 human pancreatic tumors, an antiproilferative response predominated, whereas in C32 human melanoma, marked induction of apoptosis was observed. The heterogeneity of histological changes associated with antitumor effects suggested that R115777, and possibly farnesyl protein transferase inhibitors as a class, alter processes of transformation related to tumor-host interactions in addition to inhibiting tumor-cell proliferation. PMID- 11196151 TI - Expression of a truncated first exon BCR sequence in chronic myelogenous leukemia cells blocks cell growth and induces cell death. AB - We have shown that a deletion mutant form of Bcr [Bcr(64-413)] is a strong inhibitor of the tyrosine kinase of Bcr-Abl in vitro and also inhibits its oncogenic growth effects (Liu et al., Cancer Res., 56: 5120-5124, 1996). To determine the effects of this Bcr-Abl kinase inhibitor on chronic myelogenous leukemia (CML) cells, we cloned BCR(64-413) into a recombinant, replication defective adenovirus to express useful quantities of Bcr(64-413) in a wide variety of cells in culture. Infection of Cos1 cells with plaque-purified virus at a multiplicity of infection of 20-40 induced high expression of Bcr(64-413) as detected by Western blotting. Infection of hematopoietic cells at modest multiplicities of infection (20-40) required special conditions involving shifting cycling cells to a nongrowing condition involving serum starvation and cell crowding. Under these conditions, both Bcr-Abl-positive and -negative hematopoietic cells can be efficiently infected by adenovirus, as demonstrated by 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside staining of cells infected by beta-galactosidase (beta-GAL) adenovirus. We found that expression of Bcr(64-413) in Bcr-Abl-positive K562 and BV-173 cells, but not Bcr-Abl-negative SMS-SB cells, increased cell-cell clumping and inhibited cell growth. In contrast to the effects of the Bcr(64-413) adenovirus, the beta-GAL adenovirus, despite infecting both types of cells, did not block growth or increase cell-cell clumping of Bcr Abl-positive and -negative hematopoietic cells. Expression of Bcr(64-413) protein in primary cultures of cells from CML patients with active disease interfered with cell growth, induced apoptosis (as measured by annexin staining), and increased cell-cell clumping, whereas the beta-GAL adenovirus and mock-infected cells lacked these effects. In contrast, normal marrow cells did not exhibit these effects on infection with Bcr(64-413) adenovirus. We conclude from these findings that Bcr(64-413) interferes with the oncogenic effects of Bcr-Abl and therefore has the potential for use in therapy of CML. PMID- 11196152 TI - Usefulness of repeated direct intratumoral gene transfer using hemagglutinating virus of Japan-liposome method for cytosine deaminase suicide gene therapy. AB - To investigate the feasibility of repeated gene transfection in suicide gene therapy against human solid tumors by a combination of 5- fluorocytosine (5-FC) and its converting enzyme, cytosine deaminase (CD), we repeatedly transfected the yeast CD gene into the human pancreatic cancer cell line BXPC3 using the hemagglutinating virus of Japan-liposome in a new gene transfer method. The in vivo growth of the s.c. transplanted BXPC3 tumor in nude mice given CD-gene transfection was significantly suppressed by i.p. injection of 5-FC when compared with tumors treated with the control vector. Furthermore, the tumor transfected with the CD gene during a 7-day interval was suppressed much more than that of a single transfection. These results suggest that repeated transfection of the suicide gene together with the combination of 5-FC and the yeast CD gene using the hemagglutinating virus of Japan-liposome gene transfer method may be useful for the treatment of human solid tumors, including pancreatic cancer. PMID- 11196153 TI - Mitochondrial dysfunction after aerobic exposure to the hypoxic cytotoxin tirapazamine. AB - Tirapazamine (TPZ) is a bioreductive drug that exhibits a high degree of selective toxicity toward hypoxic cells, and at doses that are used clinically, little or no cell killing is observed in aerobic cells. Nonetheless, the effects of TPZ on aerobic tissues are still responsible for the dose limitations on the clinical administration of this drug. Clinical side effects include fatigue, muscle cramping, and reversible ototoxicity. We have investigated TPZ-induced changes in the mitochondria in aerobically exposed cells as a potential mediator of these side effects. Our data show that aerobic administration of TPZ at clinically relevant doses results in a profound loss in the mitochondrial membrane potential (MMP). We show that loss in the MMP occurs in a variety of cell lines in vitro and also occurs in muscle tissues in vivo. The loss in MMP is temporary because recovery occurs within 2 h. TPZ is directly metabolized within mitochondria to a DNA-damaging form, and this metabolism leads to both the cell killing effects of TPZ on aerobic cells at high doses and to the loss in MMP at clinically relevant doses. Using cell lines derived from genetically modified mice with a targeted deletion in manganese superoxide dismutase, we have further distinguished the phenotypic effects of TPZ in mitochondria at high toxic doses versus those at clinically relevant doses. We have investigated several potential mechanisms for this TPZ-induced loss in MMP. Our results indicate no change in the rate of cellular respiration in TPZ-treated cells. This implies that the loss in MMP results from an inability of the inner mitochondrial membrane to sustain a potential across the membrane after TPZ treatment. Incubation of cells with an inhibitor of the mitochondrial permeability transition suggests that the loss of MMP may result from the regulated opening of a large mitochondria channel. PMID- 11196154 TI - In situ expression of soluble B7-1 in the context of oncolytic herpes simplex virus induces potent antitumor immunity. AB - In vivo delivery of immunomodulatory genes is a promising strategy for solid tumor vaccination. A drawback is that it necessitates induction of a large effect from transgene expression in a small percentage of tumor cells. Although the B7 family is known to be the most potent of the costimulatory molecules, gene transduction of B7 alone has not been effective in inducing antitumor immunity in nonimmunogenic tumors by ex vivo methods, much less in vivo. We have developed a novel approach where a gene encoding soluble B7-1, a fusion protein of the extracellular domain of murine B7-1 and the Fc portion of human IgG1, is delivered to tumor cells in vivo in the context of an oncolytic replication competent herpes simplex virus, and the gene product is secreted by tumor cells rather than expressed on the cell surface. Defective herpes simplex virus vectors containing the B7-1-immunoglobulin (B7-1-Ig) fusion transgene (dvB7Ig) were generated using G207 as a helper virus and tested in the poorly immunogenic murine neuroblastoma, Neuro2a, in syngeneic A/J mice. Intraneoplastic inoculation of dvB7Ig/G207 at a low titer successfully inhibited the growth of established s.c. tumors, despite the expression of B7-1-Ig being detected in only 1% or fewer of tumor cells at the inoculation site, and prolonged the survival of mice bearing intracerebral tumors. Immunohistochemistry of dvB7Ig/G207-inoculated tumors revealed a significant increase in CD4+ and CD8+ T-cell infiltration compared with control tumors inoculated with defective vector expressing alkaline phosphatase (dvAP/G207). The antitumor effect of dvB7Ig/G207 was not manifested in athymic mice. In vivo depletion of immune cell subsets in A/J mice further revealed that CD8+ T cells, but not CD4+ T cells, were required. Animals cured of their tumors by dvB7Ig/G207 treatment were protected against rechallenge with a lethal dose of Neuro2a cells but not SaI/N cells. The results demonstrate that the use of soluble B7-1 for immune gene therapy is a potent and clinically applicable means of in situ cancer vaccination. PMID- 11196155 TI - Tumor cell vaccine elicits potent antitumor immunity after allogeneic T-cell depleted bone marrow transplantation. AB - Allogeneic bone marrow transplantation (BMT) is currently restricted to hematological malignancies because of a lack of antitumor activity against solid cancers. We have tested a novel treatment strategy to stimulate specific antitumor activity against a solid tumor after BMT by vaccination with irradiated tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF). Using the B16 melanoma model, we found that vaccination elicited potent antitumor activity in recipients of syngeneic BMT in a time-dependent fashion, and that immune reconstitution was critical for the development of antitumor activity. Vaccination did not stimulate antitumor immunity after allogeneic BMT because of the post-BMT immunodeficiency associated with graft versus-host disease (GVHD). Remarkably, vaccination was effective in stimulating potent and long-lasting antitumor activity in recipients of T-cell-depleted (TCD) allogeneic bone marrow. Recipients of TCD bone marrow who showed significant immune reconstitution by 6 weeks after BMT developed B16-specific T-cell cytotoxic, proliferative, and cytokine responses as a function of vaccination. T cells derived from donor stem cells were, therefore, able to recognize tumor antigens, although they remained tolerant to host histocompatibility antigens. These results demonstrate that GM-CSF-based tumor cell vaccines after allogeneic TCD BMT can stimulate potent antitumor effects without the induction of GVHD, and this strategy has important implications for the treatment of patients with solid malignancies. PMID- 11196156 TI - Simultaneous treatment with 1-beta-D-arabinofuranosylcytosine and daunorubicin induces cross-resistance to both drugs due to a combination-specific mechanism in HL60 cells. AB - We have established a human myelogenous leukemia cell line (HL60/AD) that is 10 fold cross-resistant to both 1-beta-D-arabinofuranosylcytosine (ara-C) and daunorubicin; the cell line was isolated from HL60 by simultaneous treatment with these two agents at low drug concentrations attainable in clinical trials. HL60/AD was found to have multiple resistance mechanisms. With regard to ara-C, HL60/AD cells showed decreased deoxycytidine kinase activity but did not show elevation of cytidine deaminase activity or a decrease in ara-C influx. With regard to daunorubicin, a decrease in topoisomerase II activity was found. A decrease in intracellular accumulation of daunorubicin was also found. P glycoprotein was not detected, but the multidrug resistance-associated protein was expressed. Furthermore, an increase of total cellular glutathione (GSH) content was found. Interestingly, the resistance of HL60/AD cells not only to daunorubicin but also to ara-C was markedly reversed by treatment with L buthionine-(S,R)-sulfoximine (BSO), a potent inhibitor of GSH synthesis. After exposure of HL60/AD to ara-C, mitochondrial membrane potential and reactive oxygen intermediates showed no significant change, but a considerable loss of mitochondrial membrane potential and an increase in reactive oxygen intermediate generation were caused by pre-incubation with BSO. Neither elevation of GSH nor reversal of resistance by BSO was found in ara-C-resistant HL60 cells that were selected only with ara-C. These findings suggest that in addition to the summation of the mechanisms of resistance to each agent reported previously, an increased level of GSH plays an important role in the cross-resistance induced in HL60/AD cells by simultaneous exposure to both drugs. PMID- 11196157 TI - Induction of differentiation of acute promyelocytic leukemia cells by a cytidine deaminase-resistant analogue of 1-beta-D-arabinofuranosylcytosine, 1-(2-deoxy-2 methylene-beta-D-erythro-pentofuranosyl)cytidine. AB - Since the establishment of all-trans retinoic acid (ATRA) differentiation therapy, the prognosis of acute promyelocytic leukemia (APL) has improved, and APL has become a curable subtype of acute myelocytic leukemia. Complete remission can be achieved with ATRA alone, but disease-free survival is still too short because of relapse. To overcome this drawback, ATRA has been used in combination with chemotherapeutic agents such as 1-beta-D-arabinofuranosylcytosine (araC) and daunorubicin. However, growth of the APL cell lines NB4 and HT93 is less sensitive to araC than to that of other myeloid leukemia cell lines such as HL-60 and U937. ATRA effectively induced granulocytic differentiation of NB4 and HT93 cells, whereas araC did not, even in a high concentration. A cytidine deaminase resistant analogue of araC, 1-(2-deoxy-2-methylene-beta-D-erythro pentofuranosyl)cytidine (DMDC), inhibited the growth of NB4 and HT-93 cells and was also effective on HL-60 and U937 cells. The promyelocytic cell lines were induced to differentiate by DMDC and other cytidine deaminase-resistant analogues. Among them, DMDC was the most potent in inducing differentiation and inhibiting the growth of NB4 cells. The ATRA-induced differentiation of NB4 cells was not augmented by araC, whereas combined treatment with ATRA and DMDC had more than additive effects in inducing the differentiation of NB4 cells. Similar results were observed in a primary culture of leukemia cells that had been freshly isolated from APL patients. These results suggest that DMDC may play a role in the treatment of APL. PMID- 11196158 TI - Adenovirus-mediated Bax overexpression for the induction of therapeutic apoptosis in prostate cancer. AB - Using adenoviral technology, we overexpressed the proapoptotic molecules pro caspase-3, pro-caspase-7, and Bax to induce therapeutic apoptosis of prostate cancer cell lines growing in vitro and in vivo. Because overexpressed pro-caspase 3 did not undergo autocatalytic activation in any of the five prostate cancer cell lines evaluated, this strategy was unable to engage any component of the apoptotic pathway. Overexpressed pro-caspase-7 was proteolytically cleaved in LNCaP and LnCaP-Bcl-2 cells but not in PC-3, DU-145, or TsuPr(1) cells. Cleavage was associated with engagement of many components of the apoptotic pathway, including DEVDase activity, cleavage of intracellular caspase targets such as the DNA fragmentation factor and the proapoptotic Bid, release of cytochrome c from the mitochondria to the cytoplasm, and terminal deoxynucleotidyl transferase mediated nick end labeling. No apoptosis was observed in the cells where caspase 7 did not undergo autocatalytic activation. Searching for an approach that would more reliably induce therapeutic apoptosis of prostate cancer cell lines, we used a binary adenoviral system to overexpress the proapoptotic molecule Bax. Bax was dramatically overexpressed and caused apoptosis of every cell line infected by engaging the mitochondrial pathway, including proteolytic cleavage and catalytic activation of the caspases, cleavage of caspase substrates, release of cytochrome c from the mitochondria, and DNA fragmentation. Furthermore, three injections of the Bax overexpression system into PC-3 cell tumors in nude mice in vivo caused a 25% regression in tumor size corresponding to a 90% reduction relative to continued tumor growth in animals that received injections with the control binary system expressing Lac-Z. These experiments show that adenovirus-mediated Bax overexpression is capable of inducing therapeutic programmed cell death in vitro and in vivo by activating the mitochondrial pathway of apoptosis. On the basis of these studies, we conclude that manipulation of Bax expression is an attractive new gene therapy approach for the treatment of prostate cancer. PMID- 11196159 TI - More frequent beta-catenin exon 3 mutations in gallbladder adenomas than in carcinomas indicate different lineages. AB - To clarify the contribution of beta-catenin, which is related to cell adhesion and intranuclear transcription, to gallbladder carcinogenesis, we investigated its expression using immunohistochemistry, and beta-catenin exon 3 mutations by DNA direct sequencing, in 18 gallbladder adenomas and 82 adenocarcinomas. Membranous expression was significantly lower in moderately and poorly differentiated than in well-differentiated adenocarcinoma cases (P < 0.001). The gallbladder adenomas showed significantly stronger expression in the cytoplasm and the nucleus than carcinomas (P < 0.05 and P < 0.001, respectively), and exon 3 mutations were observed in 62.5% (10 of 16) of adenomas, but only 4.8% (1 of 21) of carcinomas. With beta-catenin as a molecular marker, the adenoma-carcinoma sequence can be considered to be a minor pathway in gallbladder carcinogenesis. PMID- 11196160 TI - Immunological and viral factors associated with the response of vulval intraepithelial neoplasia to photodynamic therapy. AB - Topical 5-aminolevulinic acid-based photodynamic therapy (PDT) has produced complete response rates of >90% for nonmelanoma skin carcinomas, which are mostly human papillomavirus (HPV) negative. Using a similar treatment protocol, we observed a short-term response in only one third (10 of 32) of high-grade vulval intraepithelial neoplasia (VIN 2-3) lesions. Unifocal lesions were found more responsive than multifocal and pigmented lesions. Animal model studies have suggested that long-term PDT response involves an immune reaction in which CTLs play a crucial role. In this study, we have assessed: (a) HPV infection; (b) HLA expression; and (c) immune infiltrating cells in VIN biopsies from responders and nonresponders to determine whether these factors may limit response to topical 5 aminolevulinic acid-based PDT. Tissues from normal vulva (n = 9), vulval carcinoma (n = 11), and VIN (32 patients from which 19 pre- and 43 post-PDT biopsies were taken) were investigated for immune cell infiltration and HLA class I expression by immunohistochemistry and HPV infection by PCR. There was a greater likelihood of HPV positivity associated with a lack of response of VIN to PDT (P = 0.002), and VIN nonresponders were more likely to show HLA class I loss compared with responders (P = 0.030). HLA class I down-regulation was significantly greater in the carcinomas (82%, total loss) than the VIN (28%, 19%, total loss; and 9%, allele loss; P = 0.004). None of the cases with class I down regulation responded to PDT, whereas 3 of 6 (50%) of cases that showed total class I loss subsequently developed superficial invasion. Compared with normal vulval skin, VIN lesions showed increased infiltration by CD4 (T-helper) and CD68 (macrophages) but not CD1a (Langerhans cells) or CD8 (CTLs). There was, however, a significant increase of CD8 infiltration in posttreatment VIN responders compared with nonresponders (P = 0.0001). These data clearly support the contention that high-risk HPV infection and lack of cell-mediated immunity may play a role in the observed poor response of lower genital lesions to topical PDT. PMID- 11196161 TI - A retrogen strategy for presentation of an intracellular tumor antigen as an exogenous antigen by dendritic cells induces potent antitumor T helper and CTL responses. AB - Induction of an effective antitumor response requires CD4+ helper T (Th) cells to recognize antigens on the same dendritic cells (DCs) that cross-present CTL antigens. Such cross-presentation is difficult to achieve by current tumor vaccine strategies. Here, we develop a novel "Retrogen" strategy for DCs to efficiently cross-present an intracellular tumor antigen, MAGE-3, to both MHC class I and MHC class II in a cognate manner. Specifically, the MAGE-3 gene was linked to a leader sequence at its NH2 terminus for secretion and to a cell binding domain at its COOH terminus for receptor-mediated internalization. DCs transduced with the modified MAGE-3 gene produced and secreted MAGE-3 proteins, which were efficiently taken up by DCs via receptor-mediated internalization and presented as exogenous antigens to class I and class II molecules. Immunization of mice with the transduced DCs expressing the MAGE-3 fusion protein, termed "Retrogen" for its retrograde transport/internalization after secretion, efficiently induced all arms of the adaptive antitumor immune responses. Thus, this retrogen strategy of using a unifying mechanism for DCs to cross-present an intracellular tumor antigen in a cognate manner could be generally used to improve the efficacy of tumor vaccines and immunotherapies. PMID- 11196162 TI - Histone deacetylase-targeted treatment restores retinoic acid signaling and differentiation in acute myeloid leukemia. AB - Histone deacetylase (HDAC)-dependent transcriptional repression of the retinoic acid (RA)-signaling pathway underlies the differentiation block of acute promyelocytic leukemia. RA treatment relieves transcriptional repression and triggers differentiation of acute promyelocytic leukemia blasts, leading to disease remission. We report that transcriptional repression of RA signaling is a common mechanism in acute myeloid leukemias (AMLs). HDAC inhibitors restored RA dependent transcriptional activation and triggered terminal differentiation of primary blasts from 23 AML patients. Accordingly, we show that AML1/ETO, the commonest AML-associated fusion protein, is an HDAC-dependent repressor of RA signaling. These findings relate alteration of the RA pathway to myeloid leukemogenesis and underscore the potential of transcriptional/differentiation therapy in AML. PMID- 11196163 TI - Granulocyte/macrophage-colony stimulating factor produced by recombinant avian poxviruses enriches the regional lymph nodes with antigen-presenting cells and acts as an immunoadjuvant. AB - Recombinant avian poxviruses [fowlpox and canarypox (ALVAC)], restricted for replication in nonavian cell substrates and expressing granulocyte/macrophage colony stimulating factor (avipox-GM-CSF), were evaluated for their ability to enrich an immunization site with antigen-presenting cells (APCs) and, in turn, function as biological vaccine adjuvants. Avipox-GM-CSF administered as a single s.c. injection significantly enhanced the percentage and absolute number of APCs in the regional lymph nodes that drain the injection site. Both the magnitude and duration of the cellular and phenotypic increases within the lymph nodes induced by the avipox-GM-CSF viruses were significantly (P < 0.05) greater than those measured in mice treated with four daily injections of recombinant GM-CSF protein. Temporal studies revealed that the APC enrichment of regional lymph nodes was sustained for 21-28 days after injection of the recombinant avipox virus expressing GM-CSF and, moreover, three injections of the recombinant virus could be given without any appreciable loss of in vivo bioactivity. Mice expressing human carcinoembryonic antigen (CEA) as a transgene (CEA.Tg) developed CEA-specific humoral and cell-mediated immunity after being immunized with avipox CEA. The coadministration of recombinant avipox viruses expressing CEA and GM-CSF significantly enhanced CEA-specific host immunity with an accompanying immunotherapeutic response in tumor-bearing CEA.Tg mice. The optimal use of avipox-GM-CSF, in terms of dose and dose schedule, especially when used with different immunogens, remains to be determined. Nonetheless, the present findings demonstrate: (a) the effective delivery of GM-CSF to an immunization site using a recombinant avian poxvirus; (b) the compatibility of delivering an antigen and GM CSF in replication-defective viruses to enhance antigen-specific immunity; and (c) the combined use of recombinant avipox viruses expressing CEA and GM-CSF to generate antitumor immunity directed at a self tumor antigen. PMID- 11196164 TI - Persistence of immunogenic pulmonary metastases in the presence of protective anti-melanoma immunity. AB - We have developed a murine melanoma model that allows us to investigate the mechanisms by which spontaneous, immunogenic melanoma metastases escape immunological destruction in syngeneic mice. In the current study, we tested the hypothesis that loss of immunogenicity is an obligatory step in the persistence of pulmonary metastases. Fragments of syngeneic K1735-M2 tumor were implanted in the outer edge of one pinna per C3H/HeN mouse, and the growing tumors were removed 2-3 weeks later. Two weeks after removal of the tumors, the mice demonstrated effective T-cell-mediated immunity to s.c. challenge with K1735-M2 cells. However, lung metastases appeared in 23% of the immunized mice within 9-12 weeks after the initial tumor implantation. The expression of protective immunity to s.c. tumors required the presence of both CD4+ and CD8+ T cells. The immunized mice had specific CTLs capable of killing both K1735-M2 melanoma cells and the cells of nine independently derived melanoma metastases. Furthermore, K1735-M2 immunization protected these mice from s.c. tumor challenge with all nine metastatic cell lines. Our results demonstrate that the persistence of these metastases within the lung was not attributable to emergence of antigen-loss variants in immunized hosts. Our model provides an approach to investigate other mechanisms by which spontaneous metastases escape from immunological control and an opportunity to improve immunotherapy of melanoma metastases. PMID- 11196165 TI - Human heat shock protein 70 peptide complexes specifically activate antimelanoma T cells. AB - Members of the heat shock protein 70 (HSP70) family display a broad cellular localization and thus bind a repertoire of chaperoned peptides potentially derived from proteins of different cellular compartments. In this report, we show that HSP70 purified from human melanoma can activate T cells recognizing melanoma differentiation antigens in an antigen- and HLA class I-dependent fashion. HLA class I-restricted anti-melanoma T cells were susceptible to MHC-restricted, HSP70-dependent stimulation, indicating that HSP70 complexed peptides were able to gain access to the class I HLA presentation pathway. In addition, MHC matching between the melanoma cells used as a source of HSP and the responding T cells were not required, indicating that HSP70 activation may occur across MHC barriers. Besides the MHC-restricted and peptide-dependent activation pathway, HSP70 with no endogenous complexed peptides or HSP70 purified from antigen negative cells was also able to induce IFN-gamma release by antimelanoma T cells by a MHC-independent mechanism. In this case, however, higher doses of HSP70 were required. The capacity to activate class I-restricted, antitumor T cells as well as antigen-presenting cells, together with the finding that the HSP70 chaperoned peptide repertoire includes melanoma-shared epitopes, holds promise for a HSP70 based cancer vaccine. PMID- 11196166 TI - Local administration of dendritic cells inhibits established breast tumor growth: implications for apoptosis-inducing agents. AB - Dendritic cells (DCs) can efficiently acquire foreign antigen(s) from apoptotic cells and induce MHC class I-restricted, antigen-specific CTLs. An accumulation of DCs within solid tumor masses in situ has been associated indirectly with a more favorable prognosis. Therefore, DCs may offer an efficient means for triggering immune responses within tumors, particularly in those masses containing significant apoptosis. We examined whether delivery of DCs could, alone, impact on the progressive growth of a tumor with a relatively high apoptotic index. We detected significant early apoptosis within the mass of a s.c. growing murine MT-901 breast carcinoma. DCs could efficiently engulf MT-901 tumor apoptotic cells in vitro. Intratumoral injections of syngeneic but not allogeneic DCs resulted in significant inhibition of MT-901 tumor growth. Histological examination of the tumor revealed intense mononuclear cell infiltration during and after DC injections. Tumor growth inhibition was relatively radiosensitive and dependent on host-derived CD8+ T cells. The baseline level of tumor apoptosis could be increased substantially by tumor necrosis factor alpha administration, leading to a greater DC-mediated antitumor effect. The antitumor effect could also be enhanced by first pulsing DCs with the foreign helper protein, keyhole limpet hemocyanin, prior to intratumoral delivery and combining it with the systemic administration of interleukin 2. Splenocytes from treated animals showed heightened levels of specific CTL activity and production of cytokines. The level of in situ tumor apoptosis appears to play a critical role in DC-mediated antitumor effects. The potential implication of these findings in DC-based tumor therapy strategies is discussed. PMID- 11196167 TI - Alterations of the double-strand break repair gene MRE11 in cancer. AB - MRE11 plays a role in DNA double-strand break repair. Hypomorphic mutations of MRE11 have been demonstrated in ataxia-telangiectasia (AT)-like disorder. ATM mutations play a causal role in AT and have been demonstrated in lymphoid malignancies in patients without AT histories. By analogy with the relationship of ATM to lymphoid malignancies, it is probable that alterations of MRE11 are associated with tumor formation. We performed a mutation analysis of MRE11 in 159 unselected primary tumors. Three missense mutations at conserved positions were found in breast and lymphoid tumors. Additionally, an aberrant transcript without genomic mutation was found in a breast tumor. These findings suggest an occasional role for MRE11 alterations in the development of primary tumors. PMID- 11196168 TI - A novel role of metalloproteinase in cancer-mediated immunosuppression. AB - Depressed immune responses have been observed frequently in cancer patients. In a variety of human malignancies, the expression of interleukin-2 receptor alpha (IL 2R alpha) on activated tumor-infiltrating lymphocytes was down-regulated. Because IL-2R alpha plays a pivotal role in the development and propagation of functional T cells, its depressed expression may result in poor function of tumor-reactive cytotoxic lymphocytes. For elucidating the mechanism responsible for down regulation of IL-2R alpha, a coculture model of in vitro mixed autologous lymphocytes and tumor cells was established. Kinetic analysis showed that cervical cancer cells down-regulated IL-2R alpha expression on encountered T cells. The amount of IL-2R alpha mRNA in tumor-infiltrating lymphocytes-derived CD8+ T cells was compatible with that in the corresponding activated CD8+ T cells. Additional evidence showed that cervical cancer cells could induce the release of soluble IL-2R alpha expression on encountered T cells. By using protease inhibition assays we demonstrated that tissue inhibitors of metalloproteinase abrogated the cancer-mediated IL-2R alpha proteolytic process and restored the T-cell proliferation function. Immunohistochemical stainings further revealed prominent metalloproteinase (MMP) expressions, including MMP-1, MMP-2, and MMP-9, in cervical cancer tissues. Additional in vitro studies showed that MMP-9 mediates cleavage of IL-2R alpha and down-regulates the proliferative capability of cancer-encountered T cells. Our findings suggest a new role of MMPs in tumor-mediated immunosuppression and provide a possible therapeutic potential for patients with cervical cancer. PMID- 11196169 TI - The chemotherapeutic drug 5-fluorouracil induces apoptosis in mouse thymocytes in vivo via activation of the CD95(APO-1/Fas) system. AB - The CD95/CD95 ligand (CD95L) system has been shown to mediate chemotherapeutic drug-induced apoptosis in vitro. However, the contribution of the CD95 pathway to drug-induced apoptosis is controversial. We have shown previously that 5 fluorouracil (5-FU) induces apoptosis in vitro via the activation of the CD95/CD95L system. To study the effects of the chemotherapeutic drug 5-FU and the contribution of the CD95 system to 5-FU-induced apoptosis in vivo, we gave mice an i.p. injection of 5-FU. Apoptotic cell death peaked in thymocytes at 18 h after administration of 5-FU. Total organ weight and cell number in the thymus were reduced by approximately 40%. This cell loss was due to apoptosis, as measured in cell suspensions by measuring hypodiploid DNA content and by terminal deoxynucleotidyl transferase-mediated nick end labeling staining of tissue sections. The number of apoptotic cells correlated with the extent of weight loss and cell attrition of the organs. Furthermore, in the thymi of 5-FU-treated animals, CD95L was strongly up-regulated. Apoptosis of thymocytes was blocked in vivo with neutralizing anti-CD95L antibodies. In addition, cell loss in the thymus was negligible in lpr mice in comparison with wild-type mice. Thus, a significant portion of apoptosis of thymocytes in vivo on treatment with 5-FU is mediated via the CD95/CD95L pathway. Our findings therefore contribute to the understanding how chemotherapeutic drugs exert their effects in vivo. PMID- 11196170 TI - Aberrant promoter methylation of multiple genes in non-small cell lung cancers. AB - Aberrant methylation of CpG islands acquired in tumor cells in promoter regions is one method for loss of gene function. We determined the frequency of aberrant promoter methylation (referred to as methylation) of the genes retinoic acid receptor beta-2 (RARbeta), tissue inhibitor of metalloproteinase 3 (TIMP-3), p16INK4a, O6-methylguanine-DNA-methyltransferase (MGMT), death-associated protein kinase (DAPK), E-cadherin (ECAD), p14ARF, and glutathione S-transferase P1 (GSTP1) in 107 resected primary non-small cell lung cancers (NSCLCs) and in 104 corresponding nonmalignant lung tissues by methylation-specific PCR. Methylation in the tumor samples was detected in 40% for RARbeta, 26% for TIMP-3, 25% for p16INK4a, 21% for MGMT, 19% for DAPK, 18% for ECAD, 8% for p14ARF, and 7% for GSTP1, whereas it was not seen in the vast majority of the corresponding nonmalignant tissues. Moreover, p16INK4a methylation was correlated with loss of p16INK4a expression by immunohistochemistry. A total of 82% of the NSCLCs had methylation of at least one of these genes; 37% of the NSCLCs had one gene methylated, 22% of the NSCLCs had two genes methylated, 13% of the NSCLCs had three genes methylated, 8% of the NSCLCs had four genes methylated, and 2% of the NSCLCs had five genes methylated. Methylation of these genes was correlated with some clinicopathological characteristics of the patients. In comparing the methylation patterns of tumors and nonmalignant lung tissues from the same patients, there were many discordancies where the genes methylated in nonmalignant tissues were not methylated in the corresponding tumors. This suggests that the methylation was occurring as a preneoplastic change. We conclude that these findings confirm in a large sample that methylation is a frequent event in NSCLC, can also occur in smoking-damaged nonmalignant lung tissues, and may be the most common mechanism to inactivate cancer-related genes in NSCLC. PMID- 11196171 TI - Transforming growth factor-beta-induced growth inhibition in a Smad4 mutant colon adenoma cell line. AB - Transforming growth factor-beta (TGF-beta) inhibits growth and induces apoptosis of colon epithelial cells. Binding of TGF-beta to its receptor induces phosphorylation of the Smad proteins Smad2 and Smad3, which then form heteromeric complexes with Smad4, translocate to the nucleus, and activate gene transcription. Smad4 function has been considered an obligate requirement for TGF beta signaling, and Smad4 mutations present in some cancers have been considered sufficient to inactivate TGF-beta signaling. In this work, we describe studies with a nontransformed human colon epithelial cell line that is mutant for Smad4 but remains growth-inhibited by TGF-beta. The colon cell line VACO-235 has lost one of its Smad4 alleles via a chromosome 18q deletion. The remaining allele bears two missense point mutations located in regions important for Smad4 trimer formation, which is thought necessary for Smad4 function. As expected, pSBE4 BV/Luc, a Smad4-activated transcriptional reporter, was inactive in VACO-235. Nonetheless, VACO-235 demonstrated 80% growth inhibition in response to TGF-beta, as well as retention of some TGF-beta-mediated activation of the p3TP-Lux transcriptional reporter. Transient transfection of the VACO-235 Smad4 mutant allele into a Smad4-null cell line confirmed that this allele is functionally inactive as assayed by both the pSBE4-BV and p3TP-Lux reporters. The simplest explanation of these results is that there is a non-Smad4-dependent pathway for TGF-beta-mediated signaling and growth inhibition in VACO-235 cells. PMID- 11196172 TI - A role for CCAAT/enhancer binding protein beta-liver-enriched inhibitory protein in mammary epithelial cell proliferation. AB - The transcription factor, CCAAT/enhancer binding protein beta (C/EBPbeta), regulates the expression of genes involved in proliferation and terminal differentiation. Dimerization of the dominant-negative C/EBPbeta-liver-enriched inhibitory protein (LIP) isoform with the C/EBPbeta-liver-enriched activating protein (LAP) isoform inhibits the transcriptional activation of genes involved in differentiation. Consequently, an increase in LIP levels may inhibit terminal differentiation and lead to proliferation. C/EBPbeta-LIP and LAP are crucial for mammary gland development (G. W. Robinson et al., Genes Dev., 12: 1907-1916, 1998; T. N. Seagroves et al., Genes Dev., 12: 1917-1928, 1998) and are also overexpressed in breast cancer (B. Raught et al., Cancer Res., 56: 4382-4386. 1996; C. A. Zahnow et al., J. Natl. Cancer Inst., 89: 1887-1891, 1997); however, little is known about how these isoforms differentially regulate cell cycle progression. To address this question, C/EBPbeta-LIP was overexpressed in both the mammary glands of transgenic mice and in cultured TM3 mammary epithelial cells. Here we report that the involuted mammary glands from transgenic mice overexpressing C/EBPbeta-LIP contain both focal and diffuse alveolar hyperplasia and, less frequently, contain mammary intraepithelial neoplasias (high grade) and invasive and noninvasive carcinomas. Likewise, cultured TM3 cells, stably expressing C/EBPbeta-LIP, showed an increase in proliferation and foci formation attributable to a reentry into S-phase during cellular confluence. These results demonstrate that C/EBPbeta-LIP can induce epithelial proliferation and the formation of mammary hyperplasias and suggest that a C/EBPbeta-LIP-initiated growth cascade may be susceptible to additional oncogenic hits, which could result in the initiation and progression of neoplasia. PMID- 11196173 TI - Lack of telomerase RNA gene hTERC expression in alternative lengthening of telomeres cells is associated with methylation of the hTERC promoter. AB - The immortal phenotype of most human cancers is attributable to telomerase expression. However, a number of immortal cell lines and tumors achieve telomere maintenance in the absence of telomerase via alternative mechanisms known as ALT (alternative lengthening of telomeres). Here we show that the promoter of the telomerase RNA gene (hTERC) is methylated in three of five ALT cell lines and is associated with a total absence of hTERC expression in the three lines. Treatment with 5-azacytidine in combination with trichostatin A resulted in partial demethylation of the hTERC promoter and expression of the gene. Partial methylation was detected in tumors (5%) and in immortal cell lines (27%). Cell lines with partial methylation express hTERC. Only in ALT cell lines does there appear to be a strong correlation between hTERC promoter hypermethylation and lack of hTERC expression. PMID- 11196174 TI - Nonhomologous end-joining of ionizing radiation-induced DNA double-stranded breaks in human tumor cells deficient in BRCA1 or BRCA2. AB - Mutations in the BRCA1 or BRCA2 genes predispose to a wide spectrum of familial cancers. The functions of the proteins encoded by BRCA1 and BRCA2 remain to be elucidated, but their interaction and colocalization with hRAD51 suggest a role in homologous recombination and DNA double-strand break (DSB) repair. The role of BRCA1 and BRCA2 in the rejoining of ionizing radiation (IR)-induced DNA DSBs, which may represent a step in the overall process of repair, remains uncertain because recent reports provide conflicting results. Because elucidation of the role of these proteins in DNA DSB rejoining is important for their functional characterization, we reexamined this end point in cells with mutations in either BRCA1 or BRCA2. We show that two pancreatic carcinoma cell lines known to have either wild-type (BxPC3) or mutant forms (Capan-1) of BRCA2 rejoin IR-induced DNA DSBs to a similar extent following biphasic kinetics characterized by a fast and a slow component. Importantly, inactivation of DNA-dependent protein kinase (DNA PK) by wortmannin generates similar shifts from the fast to the slow component of rejoining in BRCA2-proficient and BRCA2-deficient cells. This suggests that the functioning of either the fast, DNA-PK-dependent component or the slow, DNA-PK independent component of rejoining is not affected by mutations in BRCA2. Also, a human breast cancer cell line with mutated BRCA1 shows normal rejoining of IR induced DNA DSBs and levels of inhibition by wortmannin commensurate with the degree of DNA-PK inhibition. These observations fail to confirm a direct role for BRCA1 or BRCA2 in the rejoining of IR-induced DSBs in the genome of human tumor cells and, as a result, an involvement in nonhomologous end-joining. They are in line with similar observations with mutants deficient in genes implicated in homologous recombination and support the view that the radiosensitivity to killing of cells deficient in BRCA1 or BRCA2 derives from defects in this repair pathway. PMID- 11196175 TI - Mutant E-cadherin breast cancer cells do not display constitutive Wnt signaling. AB - Participation of E-cadherin in the Wnt signaling pathway was suggested because of the dual role of beta-catenin in cell adhesion and the Wnt signaling cascade. Whereas beta-catenin interacts at the cell membrane with the cell adhesion protein E-cadherin, in the nucleus it activates Wnt target genes through formation of transcriptionally active complexes with members of the Tcf/Lef family of transcription factors. Here, we analyzed by PCR and direct cycle sequencing 26 human breast cancer cell lines for alterations in the E-cadherin gene. Genetic alterations were identified in eight cell lines. Five cell lines had truncating mutations, whereas three cell lines had in-frame deletions in the gene transcript and expressed mutant E-cadherin proteins at the cell membrane. Involvement of E-cadherin in the Wnt pathway was evaluated through determination of the activity of a Tcf reporter gene, which had been transiently transfected into 15 breast cancer cell lines. None of six E-cadherin mutant cell lines and four cell lines that exhibit transcriptional silencing of the E-cadherin gene showed Tcf-mediated transcriptional activation. E-cadherin wild-type cell line DU4475 exhibited constitutive Tcf-beta-catenin signaling activity and was found to express truncated APC proteins. These results indicate that if cellular transformation occurred through mutation of E-cadherin, it is not mediated via constitutive activation of the Wnt signaling pathway. PMID- 11196176 TI - High resolution allelotype of nonfunctional pancreatic endocrine tumors: identification of two molecular subgroups with clinical implications. AB - A high resolution allelotype for nonfunctional pancreatic endocrine tumors (NF PETs) has been generated by microsatellite analysis of DNA from 16 frozen cases, each probed with 394 markers. Two subgroups of NF-PETs were found. Seven cases showed frequent, large allelic deletions [loss of heterozygosity (LOH)] with an average fractional allelic loss (FAL) of 0.55, whereas nine cases showed a small number of random losses with a FAL of 0.15. Designated high or low FAL, respectively, these genetic phenotypes showed correlation with the ploidy status: high-FAL tumors were aneuploid, low-FAL were diploid. Chromosomes 6q and 11q showed LOH in >60% of cases. About 50% of cases had losses on 11p, 20q, and 21. Selected LOH analysis on an additional 16 paraffin-embedded NF-PETs confirmed the high frequency of 6q and 11q LOH. The allelotype of NF-PET is markedly different from that of either ductal or acinar tumors of the pancreas as well as from that of functional-PETs. Moreover, whereas deletions involving chromosome 11 also are a feature of functional-PETs, the involvement of chromosome 6q is characteristic of NF-PETs. Survival analysis showed that none of the single chromosomal alterations was associated with outcome, whereas ploidy status is an independent factor adding prognostic information to that furnished by the proliferative index measured by Ki-67 immunohistochemistry. PMID- 11196177 TI - Five novel hormone-responsive cell lines derived from murine mammary ductal carcinomas: in vivo and in vitro effects of estrogens and progestins. AB - We have developed an experimental model of mammary carcinogenesis in which the administration of medroxyprogesterone acetate (MPA) to female BALB/c mice induces progestin-dependent ductal metastatic mammary tumors with high levels of estrogen receptor (ER) and progesterone receptor (PR). Through selective transplants in untreated mice, we have obtained progestin-independent variants, still expressing high levels of ER and PR. Primary cultures of the MPA-induced carcinomas C4-HD and C7-HI were set up, and after 3-4 months, several different cell lines were obtained. Four of these, MC4-L1, MC4-L2, MC4-L3, and MC4-L5 were established from C4-HD and a fifth, MC7-L1, from C7-HI. All cells were of epithelial origin, as demonstrated by electron microscopy and by immunocytochemical identification of cytokeratin and cadherin. In vitro MC4-L1, MC4-L3, and MC4-L5 showed a typical epithelial morphology; when transplanted in vivo, they originated metastatic carcinomas with different degrees of differentiation. MC4-L2 and MC7-L1 deviated from the standard epithelial picture; they disclosed a spindle-shaped morphology in vitro and in vivo gave rise to a biphasic spindle cell/tubular carcinoma and an anaplastic carcinoma, respectively; both lines gave rise to metastases. This differential morphology correlated with a higher degree of aggressiveness, as compared with MC4-L1, MC4-L3, and MC4-L5. ERs and PRs were detected by binding, immunocytochemistry, and Western blot. In vitro, MC4-L2 and MC7-L1 were stimulated by MPA (nM to microM) and 17beta-estradiol (nM and 10 nM); no significant stimulation was observed in MC4-L1, MC4-L3, and MC4-L5 under the same experimental conditions. In vivo, MPA significantly stimulated tumor growth in all epithelioid lines but not in MC4-L2 and MC7-L1. A progestin-dependent growth pattern was confirmed for MC4-L1, MC4-L3, and MC4-L5 in successive transplants, whereas MC4-L2 and MC7-L1 behaved as progestin independent. This is the first description of mouse mammary carcinoma cell lines expressing ER and PR. The different in vitro hormone responses as compared with in vivo and the differential effects of 17beta-estradiol in the parental tumors and in cell lines render these lines useful tools for the in vitro and in vivo study of hormone regulation of tumor growth and metastases. PMID- 11196178 TI - Expression of cyclooxygenase 2 in human malignant melanoma. AB - Cyclooxygenase (COX)-2 is an inducible enzyme involved in production of prostaglandins in inflammatory processes. There is now increasing evidence that a constitutive expression of COX-2 plays a role in development and progression of malignant epithelial tumors. In the present study we investigated expression and function of COX-2 in malignant melanoma. Expression of COX-2 was determined by immunohistochemistry in 28 cases of primary skin melanoma and 4 benign nevi. We show that COX-2 was expressed in 26 cases (93%) of melanomas, with a moderate to strong expression in 19 cases (68%). Benign nevi as well as normal epithelium were negative in all cases. A constitutive expression of COX-2 mRNA and protein was found in five melanoma cell lines (A375, MeWo, SK-Mel-13, SK-Mel-28, and IGR 37) by using Northern blot as well as immunoblotting. All melanoma cell lines produced prostaglandin (PG) E2 between 468 and 3500 pg/ml as determined by ELISA. Treatment with NS-398 (50 microM), a specific inhibitor of COX-2, suppressed PGE2 production of all melanoma cell lines by 50-96%. The IC50 for inhibition of PGE2 production by NS-398 was determined as 4 microM, indicating that NS-398 acts via inhibition of the COX-2 isoenzyme. We could show that proliferation of melanoma cell lines was not influenced by treatment with NS-398 in concentrations up to 100 microM. However, NS-398 reduced Matrigel invasion of all five malignant melanoma cell lines by 50-68%. Our results indicate that COX-2 is expressed in malignant melanomas and may be involved in regulation of melanoma invasion. It remains to be investigated whether selective inhibitors of COX-2 might be useful for prevention or treatment of malignant melanoma. PMID- 11196179 TI - Modulation of tumor angiogenesis by conditional expression of fibroblast growth factor-2 affects early but not established tumors. AB - Fibroblast growth factor-2 (FGF2) is a pleiotropic heparin-binding growth factor endowed with a potent angiogenic activity in vitro and in vivo. To investigate the impact of the modulation of FGF2 expression on the neovascularization at different stages of tumor growth, we generated stable transfectants (Tet-FGF2) from the human endometrial adenocarcinoma HEC-1-B cell line in which FGF2 expression is under the control of the tetracycline-responsive promoter (Tet-off system). After transfection, independent clones were obtained in which FGF2 mRNA and protein were up-regulated compared with parental cells. Also, the conditioned medium of Tet-FGF2 transfectants caused proliferation, urokinase-type plasminogen activator up-regulation, migration, and sprouting of cultured endothelial cells. A 3-day treatment of Tet-FGF2 cell cultures with tetracycline abolished FGF2 overexpression and the biological activity of the conditioned medium without affecting their proliferative capacity. Tet-FGF2 cells formed tumors when nude mice received s.c. injections. The administration of 2.0 mg/ml tetracycline in the drinking water before cell transplantation, continued throughout the whole experiment, inhibited FGF2 expression in Tet-FGF2 tumor lesions. This was paralleled by a significant decrease in the rate of tumor growth and vascularization to values similar to those observed in lesions generated by parental HEC-1-B cells. Tetracycline administration 20 days after tumor cell implant, although equally effective in reducing FGF2 expression and inhibiting tumor vascularity, only minimally impaired the growth of established Tet-FGF2 tumors. The results indicate that FGF2 expression deeply affects the initial tumor growth and neovascularization of HEC-1-B human endometrial adenocarcinoma in nude mice. On the contrary, the growth of established tumors appears to be independent of the inhibition of FGF2 expression and decreased vascular density. The possibility that a significant reduction of angiogenesis may not affect the progression of large tumors points to the use of antiangiogenic therapy in early tumor stage. PMID- 11196180 TI - Antiapoptotic role of endogenous nitric oxide in human melanoma cells. AB - The role of endogenous NO on cell survival was investigated in human melanoma cells and melanocytes. Inducible NO synthase (iNOS) was always expressed in a panel of melanoma cell lines from metastatic lesions and in normal adult melanocytes. iNOS was also detected by immunohistochemistry in melanoma cells from metastases. Release of NO by tumor cells and melanocytes was inhibited by a specific iNOS inhibitor, aminoguanidine (AMG). Inhibition of endogenous NO synthesis did not affect cell cycle progression of melanoma cells but led to cell death by apoptosis, as indicated by Annexin V/propidium iodide and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling assays. By contrast, iNOS inhibition by AMG did not promote apoptosis in normal adult melanocytes. A mitochondrial pathway was involved in melanoma apop tosis, as indicated by altered mitochondrial membrane potential (delta psi(m)) and down-regulation of Bcl-2 protein level after iNOS inhibition. AMG treatment triggered release of caspase-1, enzymatic activation of caspase-3, and degradation of poly(ADP-ribose) polymerase, one of the main caspase-3 substrates. Melanoma cell apoptosis induced by iNOS inhibition was completely blocked by peptide inhibitors of caspase-1 and caspase-3 (Ac-DEVD-CHO and AC-YVAD-CHO) or by an exogenous NO donor, sodium nitroprusside, or by addition of serum. Finally, comparison of control and AMG treated melanoma cells by pathway-specific gene array analysis indicated that inhibition of NO synthesis led, before induction of apoptosis, to up-regulation of mRNA levels of genes involved in the apoptosis pathway such as Bax, caspase-1, caspase-3, caspase-6, gadd45beta, mdm2, and TRAIL. Taken together, these results indicate that melanoma cell survival is regulated by endogenous NO resulting from iNOS activity. PMID- 11196181 TI - p53 induction and apoptosis in response to radio- and chemotherapy in vivo is tumor-type-dependent. AB - The p53 protein rapidly accumulates in cells in response to DNA damage, which can trigger apoptosis. This pathway is hypothesized to be important for tumor suppression by p53, as well as for the response of tumors to chemo- or radiotherapy. Implicit in these ideas is that the p53 induction-apoptosis pathway is active in tumor cells in vivo. Because tumor suppression by p53 in mice is markedly tissue-type-dependent, we tested the activity of the pathway in tumors in vivo by inducing tumors in six different tissues and treating tumor-bearing mice with DNA damaging cancer therapeutic agents. In response to treatment, cells from T-cell lymphomas, intestinal adenomas, and mammary tumors rapidly induced p53 and underwent apoptosis. In squamous cell papillomas, p53 was constitutively expressed and was further induced by the treatments, but apoptotic cells were only rarely observed. In treated mice bearing lung or liver adenomas, minimal or no p53 accumulation or apoptosis was observed in the tumor cells. Thus, there is marked variation in the intrinsic ability of autochthonous tumor cells to accumulate p53 and undergo apoptosis. This variation provides one explanation for the tissue specificity of tumor suppression by p53. It also indicates that the role of apoptosis in the response of tumors to therapy varies significantly among tumor types. PMID- 11196182 TI - Specific p53 mutations detected in plasma and tumors of hepatocellular carcinoma patients by electrospray ionization mass spectrometry. AB - Hepatocellular carcinoma (HCC), a common cause of cancer deaths worldwide, has several major etiological risk factors, including infection with the hepatitis viruses and exposure to aflatoxin B1. A specific missense mutation resulting from a guanine to thymine transversion at the third position of codon 249 in the p53 tumor suppressor gene has been reported in 10-70% of HCCs from areas of high dietary exposure to aflatoxin B1. Short oligonucleotide mass analysis was compared with DNA sequencing in 25 HCC samples for specific p53 mutations. Mutations were detected in 10 samples by short oligonucleotide mass analysis in agreement with DNA sequencing. Analysis of another 20 plasma and tumor pairs showed 11 tumors containing the specific mutation, and this change was detected in six of the paired plasma samples. Four of the plasma samples had detectable levels of the mutation; however, the tumors were negative, suggesting possible multiple independent HCCs. Ten plasma samples from healthy individuals were all negative. This molecular diagnostic technique has implications for prevention trials and for the early diagnosis of HCC. PMID- 11196183 TI - Apoptosis: an early event in metastatic inefficiency. AB - Whereas large numbers of cells from a primary tumor may gain access to the circulation, few of them will give rise to metastases. The mechanism of elimination of these tumor cells, often termed "metastatic inefficiency," is poorly understood. In this study, we show that apoptosis in the lungs within 1-2 days of introduction of the cells is an important component of metastatic inefficiency. First, we show that death of transformed, metastatic rat embryo cells occurred via apoptosis in the lungs 24-48 h after injection into the circulation. Second, we show that Bcl-2 overexpression in these cells inhibited apoptosis in culture and also conferred resistance to apoptosis in vivo in the lungs 24-48 h after injection. This inhibition of apoptosis led to significantly more macroscopic metastases. Third, comparison between the extent of apoptosis by a poorly metastatic cell line to that by a highly metastatic cell line 24 h after injection in the lungs revealed more apoptosis by the poorly metastatic cell line. These results indicate that apoptosis, which occurs at 24-48 h after hematogenous dissemination in the lungs is an important determinant of metastatic inefficiency. Although prior work has shown an association between apoptosis in culture and metastasis in vivo, this work shows that apoptosis in vivo corresponds to decreased metastasis in vivo. PMID- 11196184 TI - Laminin isoforms 8 and 10 are primary components of the subendothelial basement membrane promoting interaction with neoplastic lymphocytes. AB - To determine whether subendothelial laminins (LNs) could be implicated in the extravasation of neoplastic lymphocytes, we have examined the distribution of a number of LN isoforms in human vascular structures of adult individuals and have assayed the ability of the isolated LN molecules to promote adhesion of lymphoma and leukemic cells in vitro using a novel cell adhesion assay, CAFCA, Centrifugal Assay for Fluorescence-based Cell Adhesion (E. Giacomello et al., Biotechniques, 26: 758-762, 1999; P. Spessotto et al., Methods Mol. Biol., 139: 321-343, 2000). The use of previously characterized LN chain-specific antibodies showed that the vast majority of the smaller vascular compartments, known to correspond to sites of lymphocyte transmigration, expressed the subunits involved in the structuring of 9 of the 12 LN isoforms known to date. Eight LN isoforms (i.e., LN-1, -2, -4, 5, -8, -9, -10, and -11) and four naturally occurring LN complexes were isolated from various tissues and cultured cells by combined gel filtration, ion exchange, and immunoaffinity chromatographies, and the identity/composition of the isolated LNs/LN complexes was asserted by immunochemical means and amino-acid sequencing. Notwithstanding the widespread colocalization of LN isoforms, a panel of neoplastic B- and T-cell lines and lymphocytes isolated from patients affected by chronic lymphocytic B-cell leukemia attached preferentially and with high avidity to purified LN-8, purified LN-10, and LN-10-containing protein complexes, whereas lymphocytes derived from patients diagnosed with acute lymphocytic leukemia failed to bind to these LNs. All of the tested neoplastic lymphocytes failed to adhere to the isolated LN-1, LN-4, LN-9, and LN-11 and attached moderately well to purified LN-2 and LN-5. The interaction of transformed lymphocytes with LNs was cation-dependent and interchangeably mediated by the alpha3beta1 and alpha6beta1 integrins. The degree of engagement of the two LN receptors was dependent upon their relative levels of cell surface expression, whereas, irrespective of the phenotype, lymphocytes deprived of either of these receptors were incapable of LN binding. The findings suggest that LN-8 and LN-10 may act in an independent or complementary fashion as primary components of the endothelial basement membrane favoring the interaction of extravasating neoplastic lymphocytes. Thus, our results would demonstrate that different LN isoforms may evoke diverse cellular responses in different cell types and that this divergence may be the basis for the redundancy of LN distribution in a number of vascular structures. PMID- 11196185 TI - Reconstitution of caspase 3 sensitizes MCF-7 breast cancer cells to doxorubicin- and etoposide-induced apoptosis. AB - MCF-7, a breast cancer-derived cell line, is deficient of caspase 3 and relatively insensitive to many chemotherapeutic agents. To study the association of caspase 3 deficiency and chemotherapeutic resistance, we reconstituted caspase 3 in MCF-7 cells and characterized their apoptotic response to doxorubicin and etoposide. Western blots demonstrated that caspase 3 was constitutively expressed in the reconstituted MCF-7 cells. Both morphological observation and survival assays showed that caspase 3 reconstitution significantly sensitized MCF-7 cells to both drugs. Remarkably increased activation of caspases 3, 6, and 7, cleavage of cellular death substrates, and DNA fragmentation were detected in the reconstituted MCF-7 cells after drug treatment. Together, these data demonstrated a specific role for caspase 3 in chemotherapy-induced apoptosis and in activation of caspases 6 and 7. Our results also suggest that caspase 3 deficiency may contribute to chemotherapeutic resistance in breast cancer. PMID- 11196186 TI - Cytogenetic analysis of multifocal bladder cancer supports a monoclonal origin and intraepithelial spread of tumor cells. AB - Bladder cancer is often characterized by a multifocal growth pattern. This observation has given rise to the hypothesis of "field cancerization," predicting a polyclonal origin of multiple tumors rising from an area of independently transformed mucosa cells. On the other hand, genetic studies suggested a monoclonal origin. To address these contradictory hypotheses, we performed comparative genomic hybridization (CGH) on 32 tumors originating from six bladder cystectomy specimens. All tumors derived from the same patient showed a set of 7 13 identical chromosomal aberrations and additional individual alterations. Most striking were the findings of 17p losses in all (32 of 32) tumors of the six cystectomy specimens and 20p gains in all tumors of four bladders, as well as an unexpected high number of chromosomal changes (20.4 alterations per tumor on average). To clarify a possible role of the TP53 tumor suppressor gene on 17p13, we applied immunohistochemistry and sequence analysis on the tumors and additional 52 mucosa samples. Identical TP53 mutations and protein overexpression was found in individual tumors only as well as in mucosa samples from continuous areas. Our results not only provide further evidence for a monoclonal origin of multifocal bladder cancer but also point at intraepithelial migration of tumor cells carrying specific chromosomal aberrations. PMID- 11196187 TI - Frameshift mutations at coding mononucleotide repeats of the hRAD50 gene in gastrointestinal carcinomas with microsatellite instability. AB - Microsatellite instability (MSI) and frameshift mutations in genes containing nucleotide repeats have been reported in a subset of colorectal and gastric carcinomas. This study describes the analysis of MSI-positive colorectal (39 cases) and gastric carcinomas (36 cases) for the presence of frameshift mutations of the six genes known to be involved in DNA repair and containing mononucleotide repeats in their coding region. Our mutational study of the 75 MSI-positive tumors revealed frequent mutations in hRAD50 (23 cases, 31%), BLM (16 cases, 21%), and hMSH6 (16 cases, 21%); rare mutations in BRCA1 (1 case, 1%) and ATM (3 cases, 4%); and no mutation in NBS1. In contrast, no frameshift mutation was found in 60 MSI-negative colorectal and gastric carcinomas. The mutation of hRAD50, a gene that is involved in the response to cellular DNA damage and forms a complex with hMRE11 and NBS1, has not been reported previously. Our results suggest that frameshift mutations of hRAD50, BLM, and hMSH6 are selected and play a role in the tumorigenesis of colorectal and gastric carcinomas with MSI. The MSI targeting of the hRAD50 and BLM genes represents an additional link between MSI and DNA repair because alteration of these genes could accelerate defective DNA repair. PMID- 11196188 TI - Neuroblastoma-derived gangliosides inhibit dendritic cell generation and function. AB - Neuroblastoma (NB), a tumor of the sympathetic nervous system, is the most common extracranial solid tumor in children. NB-derived gangliosides inhibit the functional activity of T and natural killer cells, contribute to tumor-induced bone marrow suppression, and cause multiple alterations of hematopoiesis, resulting in pancytopenia. However, the role of gangliosides in the regulation of dendritic cell (DC) generation (dendropoiesis) has not been studied. Using murine and human NB cell lines, we demonstrated that coincubation of murine bone marrow progenitors or human CD34+ progenitor cells with NB cells resulted in a significant inhibition of dendropoiesis in vitro up to 90%. The number of DCs was assessed by FACScan determination of CD83+ or CD11c+ cells coexpressing MHC class II and CD86 molecules. In addition, inhibition of antigen-presenting properties of DCs cultured in the presence of NB cells was observed in allogeneic mixed leukocyte reaction (33,508 +/- 1,613 cpm for control DCs versus 17,428 +/- 152 cpm for NB-treated DCs; P < 0.05). Treatment of NB cells with 10 microM DL-threo 1-phenyl-2-decanolylamine-3-morpholino-1-propanol HCl, an inhibitor of glucosylceramide synthase, markedly abrogated ganglioside synthesis and was accompanied by blockade of NB ability to inhibit dendropoiesis. Furthermore, purified gangliosides added to DC cultures significantly inhibited DC generation. The percentage of CD83+ cells decreased from 51.8 +/- 6.1% in the control group to 12.9 +/- 2.7% in cultures treated with GD2 (P < 0.05). Thus, our results demonstrate that NB-derived gangliosides inhibit the generation of functionally active DCs and may play a role in tumor-induced immunosuppression and subsequent tumor escape from immune recognition and elimination. PMID- 11196189 TI - Specifically targeted killing of carcinoembryonic antigen (CEA)-expressing cells by a retroviral vector displaying single-chain variable fragmented antibody to CEA and carrying the gene for inducible nitric oxide synthase. AB - The generation of retroviral vectors that infect specific cell types through recognition of cell surface antigens is a promising and effective approach to targeted gene therapy of cancer. Carcinoembryonic antigen (CEA), a highly characterized, cell surface glycoprotein overexpressed by various tumor cells, provides a specific tool for tumor tissue-specific targeting by retroviral vectors. The conventional suicidal gene delivery systems need additional drugs other than their gene products. The inducible nitric oxide synthase (iNOS) gene product yields nitric oxide (NO), which directly induces autocytotoxicity and cytolysis of bystander cells. In the present study, we have developed a novel bifunctional Moloney murine leukemia virus-based recombinant retroviral vector that displays a chimeric envelope protein containing a single-chain variable fragmented (scFv) antibody to CEA and carries the iNOS gene in the genome. The resultant bifunctional retroviral vector showed a specific delivery of the iNOS gene to human CEA-expressing carcinoma cells, resulting in the direct and efficient killing of CEA-expressing carcinoma cells by induction of apoptosis. This is the first report of successful killing of CEA-expressing cells by specific targeting of the iNOS gene. This approach may offer a one-step procedure for effective gene therapy of CEA-expressing tumors. PMID- 11196190 TI - Matrix metalloproteinase 2 in tumor cell-induced platelet aggregation: regulation by nitric oxide. AB - A correlation exists between the ability of tumor cells to aggregate platelets and their tendency to metastasize. Tumor cell-induced platelet aggregation (TCIPA) facilitates the embolization of the vasculature with tumor cells and the formation of metastatic foci. It is well documented that matrix metalloproteinases (MMPs) play an integral part in tumor spread and the metastatic cascade. Therefore, we have examined the role of MMPs during TCIPA and its regulation by nitric oxide (NO) in vitro. Human HT-1080 fibrosarcoma and A549 lung epithelial cancer cells induced TCIPA in a concentration-dependent manner that was monitored by aggregometry. This aggregation resulted in the release of MMIP-2 from platelets and cancer cells, as measured by zymography. HT-1080 cells released significantly more MMP-2 than A549 cells and were more efficacious in inducing TCIPA. Inhibition of MMP-2 with phenanthroline (1-1000 microM), a synthetic inhibitor of MMPs, and by neutralizing anti-MMIP-2 antibody (10 microg/ml) reduced TCIPA induced by HT-1080 cells. TCIPA was abolished by simultaneous inhibition of platelet function with acetylsalicylic acid (100 microM; thromboxane pathway inhibitor), apyrase (250 microg/ml; ADP pathway inhibitor), and phenanthroline. NO donors such as S-nitroso-n-acetylpenicillamine and S-nitrosoglutathione (both at 0.01-100 microM) inhibited TCIPA and MMP-2 release from platelets and tumor cells. The inhibitory actions of S-nitroso-n acetylpenicillamine and S-nitrosoglutathione were reversed by 1H [1,2,4]oxadiazole[4,3]quinoxalin-1-one (0.01-30 microM), a selective inhibitor of the soluble guanylyl cyclase. We conclude that (a) human fibrosarcoma cells aggregate platelets via mechanism(s) that are mediated, in part, by MMP-2; (b) NO inhibits TCIPA, in part, by attenuating the release of MMP-2; and (c) these effects of NO are cGMP-dependent. PMID- 11196191 TI - Interleukin 6 inhibits proliferation and, in cooperation with an epidermal growth factor receptor autocrine loop, increases migration of T47D breast cancer cells. AB - Interleukin (IL)-6, a multifunctional regulator of immune response, hematopoiesis, and acute phase reactions, has also been shown to regulate cancer cell proliferation. We have investigated IL-6 signaling pathways and cellular responses in the T47D breast carcinoma cell line. The IL-6-type cytokines, IL-6 and oncostatin M, simultaneously inhibited cell proliferation and increased cell migration. In T47D cells, IL-6 stimulated the activation of Janus-activated kinase 1 tyrosine kinase and signal transducers and activators of transcription (STAT) 1 and STAT3 transcription factors. Expression of dominant negative STAT3 in the cells strongly reduced IL-6-mediated growth inhibition but did not prevent IL-6-induced cell migration. IL-6 treatment led to activation of the mitogen activated protein kinase (MAPK) and the phosphatidylinositol 3'-kinase (PI3K) pathways. Inhibition of MAPK or PI3K activity reversed IL-6- and oncostatin M stimulated migration. Because cross-talk between cytokine receptors and members of the ErbB family of receptor tyrosine kinases has been described previously, we have examined their interaction in T47D cells. Down-regulation of ErbB receptor activity, through the use of specific pharmacological inhibitors or dominant negative receptor constructs, revealed that IL-6-induced MAPK activation was largely dependent on epidermal growth factor (EGF) receptor activity, but not on ErbB-2 activity. Using a monoclonal antibody that interferes with EGF receptor ligand interaction, we have shown that in T47D cells, IL-6 cooperates with an EGF receptor autocrine activity loop for signaling through the MAPK and PI3K pathways and for cell migration. Both the tyrosine phosphatase SHP-2 and the multisubstrate docking molecule Gab1, which are potential links between IL-6 and the MAPK/PI3K pathways, were constitutively associated with the active EGF receptor. On IL-6 stimulation, SHP-2 and Gab1 were recruited to the gp130 subunit of the IL-6 receptor and tyrosine phosphorylated, allowing downstream signaling to the MAPK and PI3K pathways. Thus, in T47D breast carcinoma cells, IL-6 acts in synergy with EGF receptor autocrine activity to signal through the MAPK/PI3K pathways. Cooperation between IL-6 and the EGF receptor in T47D breast carcinoma cells illustrates how a combination of multiple stimuli, either exogenous or endogenous, may result in synergistic cellular responses. PMID- 11196192 TI - Vascular endothelial growth factor receptor-2-blocking antibody potentiates radiation-induced long-term control of human tumor xenografts. AB - Antiangiogenic therapy can enhance radiation-induced tumor growth inhibition. However, the effects of combined antiangiogenic and radiation therapy on long term tumor control and normal tissue response have not been reported. We treated mice bearing two different human tumor xenografts with anti-vascular endothelial growth factor receptor-2 antibody (DC101) and five dose fractions of local radiation and followed them for at least 6 months. DC101 significantly decreased the dose of radiation necessary to control 50% of tumors locally. The decrease was 1.7- and 1.3-fold for the moderately radiosensitive small cell lung carcinoma 54A and the highly radioresistant glioblastoma multiforme U87, respectively. In contrast to tumors, no increase in skin radiation reaction by the antibody was detected. Surprisingly, 44% of mice bearing 54A tumor developed clear ascites after DC101 treatment at its highest dose; this was fatal to 20% of mice. This adverse effect was seen only in mice that received whole-body irradiation 1 day before tumor implantation. The encouraging results on two human tumor xenografts suggest that vascular endothelial growth factor receptor-2 blockade merits further investigation to assess its potential as an enhancer of radiation therapy in the clinic. PMID- 11196193 TI - D-24851, a novel synthetic microtubule inhibitor, exerts curative antitumoral activity in vivo, shows efficacy toward multidrug-resistant tumor cells, and lacks neurotoxicity. AB - N-(pyridin-4-yl)-[1-(4-chlorbenzyl)-indol-3-yl]-glyoxyl-amid (D-24851) is a novel synthetic compound that was identified in a cell-based screening assay to discover cytotoxic drugs. D-24851 destabilizes microtubules and blocks cell cycle transition specifically at G2-M phase. The binding site of D-24851 does not overlap with the tubulin binding sites of known microtubule-destabilizing agents like vincristine or colchicine. In vitro, D-24851 has potent cytotoxic activity toward a panel of established human tumor cell lines including SKOV3 ovarian cancer, U87 glioblastoma, and ASPC-1 pancreatic cancer cells. In vivo, oral D 24851 treatment induced complete tumor regressions (cures) in rats bearing Yoshida AH13 sarcomas. Of importance is that the administration of curative doses of D-24851 to the animals revealed no systemic toxicity in terms of body weight loss and neurotoxicity in contrast to the administration of paclitaxel or vincristine. Interestingly, multidrug-resistant cell lines generated by vincristine-driven selection or transfection with the Mr 170,000 P-glycoprotein encoding cDNA were rendered resistant toward paclitaxel, vincristine, or doxorubicin but not towards D-24851 when compared with the parental cells. Because of its synthetic nature, its oral applicability, its potent in vitro and in vivo antitumoral activity, its efficacy against multidrug-resistant tumors, and the lack of neurotoxicity, D-24851 may have significant potential for the treatment of various malignancies. PMID- 11196195 TI - Tumor progression is associated with a significant decrease in the expression of the endostatin precursor collagen XVIII in human hepatocellular carcinomas. AB - Endostatin inhibits angiogenesis and tumor growth in mice. The role of its endogenous precursor collagen XVIII in human cancer is unknown. In normal tissues, two variants of collagen XVIII, namely, the short and long forms regulate tissue specificity, the long form being almost exclusively expressed by hepatocytes in the liver. We analyzed RNA arrays from 57 hepatocellular carcinomas (HCCs) with common and variant-specific probes and investigated the relationships between collagen XVIII expression and angiogenesis by measuring the CD34-positive microvessel density. Low collagen XVIII expression by tumor hepatocytes was associated with large tumor size (r, -0.63; P < 0.001) and replacement of trabeculae with pseudoglandular-solid architecture (chi2, 28; P < 0.001), which indicate tumor progression. Tumors expressing the highest collagen XVIII levels were smaller and had lower microvessel density (P = 0.01) than those expressing moderate levels; and HCCs with the lowest collagen XVIII levels approached a plateau of microvessel density, which indicated that a decrease in collagen XVIII expression is associated with angiogenesis in primary liver cancer. HCCs recurring within 2 years of resection showed 2.2-fold lower collagen XVIII mRNA than nonrecurring ones (P = 0.02). The findings relied on the hepatocyte-specific long form. Thus, the endogenous expression of the endostatin precursor decreases along with tumor progression in HCCs. PMID- 11196194 TI - Heregulin regulation of urokinase plasminogen activator and its receptor: human breast epithelial cell invasion. AB - Heregulin-beta1, which binds human epidermal growth factor receptors 3 and 4, promotes motility and invasiveness of breast cancer cells. Considering the established role of urokinase plasminogen activator (uPA) and its receptor (uPAR) in invasion, this study was undertaken to explore the role of heregulin-beta1 in regulating uPA and uPAR in breast cancer invasion. The stimulation by heregulin beta1 of noninvasive human breast cancer MCF-7 cells induced the expression of uPA mRNA, protein, and its plasminogenic activity. This uPA mRNA expression was blocked by a transcriptional inhibitor, actinomycin D, and does require de novo protein synthesis for its optimal induction in MCF-7 cells, but not in mouse mammary epithelial HC11 cells. Heregulin-beta1 also induced the expression of uPAR mRNA and protein in an actinomycin D-sensitive manner and cycloheximide superinduced the uPAR mRNA. Heregulin-beta1-stimulated signaling initiated the transcription from uPA- and uPAR-promoters. These results suggest that heregulin beta1 regulation of breast cancer cell invasion may be mediated in part through the up-regulation of uPA and uPAR. PMID- 11196196 TI - Highly elevated ultraviolet-induced mutation frequency in isolated Chinese hamster cell lines defective in nucleotide excision repair and mismatch repair proteins. AB - We have isolated N-methyl-N'-nitro-N-nitrosoguanidine-resistant cell lines from 43-3B Chinese hamster ovary cells, which are deficient in the ERCC1 gene involved in nucleotide excision repair. By Western blotting analysis, we found cell lines that are deficient or decreased in the amount of MSH6, or PMS2, or MSH2 proteins. Cell extracts of these cell lines show reduced efficiency of G:T mismatch repair activity. Compared with 43-3B, these cell lines exhibit highly elevated UV induced mutation rates, indicating that mammalian mismatch repair can suppress UV induced mutagenesis and may play a role in the fidelity of DNA replication at the sites of UV damage. PMID- 11196197 TI - Topoisomerase I-mediated cytotoxicity of N-methyl-N'-nitro-N-nitrosoguanidine: trapping of topoisomerase I by the O6-methylguanine. AB - Alkylating agents such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) are known to covalently link alkyl groups at the position 6 of guanines (O6MG) in DNA. O6 alkylguanine-DNA alkyltransferase (AGT) specifically removes the methyl group of the O6MG. Using purified human topoisomerase I (Top1), we found an 8-10-fold enhancement of Top1 cleavage complexes when O6MG is incorporated in oligonucleotides at the +1 position relative to a unique Top1 cleavage site. Top1 poisoning by O6MG is attributable to a decrease of the Top1-mediated DNA religation as well as an increase in the enzyme cleavage step. Increased cleavage is probably linked to a change in the hydrogen bonding pattern, such as in the case of the 8-oxoguanine, whereas inhibition of religation could be attributed to altered base pairing, such as abasic sites or base mismatches, because incorporation of a 6-thioguanine did not affect Top1 activity. Top1-DNA covalent complexes are also induced in MNNG-treated CHO cells constitutively lacking the AGT enzyme. Conversely, no increase could be detected in CHO cells transfected with the wild-type human AGT. Moreover, we show that yeasts overexpressing the human Top1 are more sensitive to MNNG, whereas knock-out Top1 strain cells display some resistance to the drug. Altogether, these results suggest a role for Top1 poisoning by alkylated bases in the antiproliferative activity of alkylating agents as well as in the DNA lesions resulting from endogenous and carcinogenic DNA modifications. PMID- 11196198 TI - The partial nontandem duplication of the MLL (ALL1) gene is a novel rearrangement that generates three distinct fusion transcripts in B-cell acute lymphoblastic leukemia. AB - A partial nontandem duplication (PNTD) of mixed lineage leukemia (MLL) gene is described in B-cell acute lymphoid leukemia without structural cytogenetic abnormalities at 11q23 and 9p22. A duplicated portion of MLL is interrupted by the insertion of a region of 9p22 that includes the 3'-end of the AF9 gene. The PNTD encodes: (a) a PNTD transcript; (b) a partial tandem duplication of MLL; and (c) a chimeric transcript fusing MLL to the 3'-end of AF9, mimicking the t(9;11)(p22;q23) and expressed 1024-fold higher than the other two. The MLL PNTD, therefore, contributes toward leukemogenesis through simultaneous production of fusion transcripts that are otherwise encoded by three distinct genetic defects. PMID- 11196199 TI - Human homologue of yeast Rad23 protein A interacts with p300/cyclic AMP responsive element binding (CREB)-binding protein to down-regulate transcriptional activity of p53. AB - The tumor suppressor protein p53 regulates various cellular responses to DNA damage and plays a significant role in DNA repair. The nuclear p300/cyclic AMP responsive element binding (CREB)-binding protein (CBP) proteins act as coactivators in supporting the transcription function of p53. We examined the role of the human homologue of yeast Rad23 protein A (hHR23A), one of the two human homologues of the Saccharomyces cerevisiae nucleotide excision repair gene product Rad23, in the p300/CBP-associated regulation of p53 activity. Overexpression of wild-type hHR23A inhibits the p53 transcriptional activity and results in a decreased steady-state protein level of cellular p53. The inhibitory effect of hHR23A can be overcome by the concomitant expression of p300, CBP, and p300 segments harboring C/H1 domain and neutralized by the coexpression of HIV accessory protein Vpr, which binds COOH terminus of hHR23A/B. Additionally, hHR23A was shown to interact in vitro and in vivo with p300 segments harboring C/H1 domain. These studies provide evidence for the involvement of hHR23A in the regulation of p53 activity through p300/CBP. Although the precise direct role of hHR23 proteins in regulation of p53 and DNA repair remains to be elucidated, our data suggest that the interaction between hHR23A and p300/CBP has important implications in cross-talk between the p53 pathway and DNA repair. PMID- 11196200 TI - Intact nitric oxide synthase II gene is required for interferon-beta-mediated suppression of growth and metastasis of pancreatic adenocarcinoma. AB - Previous studies have shown that enforced expression of IFN-beta suppressed tumor growth and metastasis. In this report, we determined whether the induction of nitric oxide synthase II (NOS II) gene is required for IFN-beta-mediated antitumor activity using syngeneic mice with intact (NOS II+/+) or genetically disrupted (NOS II-/-) NOS II gene. PANC02-H7 highly metastatic murine pancreatic adenocarcinoma cells were transfected with an IFN-beta expression vector or a control pcDNA3 vector. The parental PANC02-H7, control vector-transfected, and IFN-beta-transfected cells were orthotopically implanted into the pancreas of syngeneic NOS II+/+ and NOS II-/- C57BL/6J mice. In NOS II+/+ C57BL/ 6J, both parental and control vector-transfected cells grew progressively in pancreas and produced numerous liver metastases and a large amount of malignant ascites, whereas IFN-beta-secreting cells did not. In NOS II-/- C57BL/6J mice, however, IFN-beta-secreting cells grew much more aggressively. Higher NO induction was detected in NOS II+/+ mice that received injections with IFN-beta-secreting cells than with the control cells, but it was not detected in NOS II-/- mice. These data suggested that IFN-beta secreted from tumor cells stimulates NO production by host cells and suppresses tumor growth and metastasis. PMID- 11196201 TI - Proteomic analysis reveals that 14-3-3sigma is down-regulated in human breast cancer cells. AB - The class of molecular chaperones known as 14-3-3 is involved in the control of cellular growth by virtue of its apparent regulation of various signaling pathways, including the Raf/mitogen-activated protein kinase pathway. In breast cancer cells, the sigma form of 14-3-3 has been shown to interact with cyclin dependent kinases and to control the rate of entry into mitosis. To test for a direct role for 14-3-3 in breast epithelial cell neoplasia, we have quantitated 14-3-3 protein levels using a proteomic approach based on two-dimensional electrophoresis and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF). We show here that 14-3-3sigma protein is strongly down-regulated in the prototypic breast cancer cell lines MCF-7 and MDA-MB-231 and in primary breast carcinomas as compared with normal breast epithelial cells. In contrast, levels of the alpha, beta, delta, or zeta isoforms of 14-3-3 were the same in both normal and transformed cells. The data support the idea that 14-3-3sigma is involved in the neoplastic transition of breast epithelial cells by virtue of its role as a tumor suppressor; as such, it may constitute a robust marker with clinical efficacy for this pathology. PMID- 11196202 TI - Evidence for the development of p53 mutations after cytotoxic therapy in a neuroblastoma cell line. AB - p53 mutations are rare in neuroblastomas at diagnosis perhaps accounting for their initial response to therapy, but advanced neuroblastoma frequently relapses, and it is possible that p53 mutations develop later. Two neuroblastoma cell lines derived from the same patient before [SKNBE(1n)] and after [SKNBE(2c)] cytotoxic therapy were analyzed for the presence of chromosome 17 and p53 genes by fluorescent in situ hybridization, p53 mutations by DNA sequencing, and p53 function after irradiation by studying the transcription of p53-regulated genes, cell cycle arrest, and induction of apoptosis. The SKNBE(1n) cell line was wild type for p53, had two p53 genes, two copies of chromosome arm 17p and showed functional p53 after irradiation. The SKNBE(2c) cell line derived from the same patient 5 months later at relapse had loss of an entire chromosome 17, resulting in hemizygosity for the p53 locus on 17p and a missense p53 mutation in exon 5, and p53 was not functional after irradiation. The appearance of a p53 mutation in a cell line derived from a relapsed neuroblastoma suggests that this may be a mechanism of resistance to therapy. If p53 mutations develop frequently in relapsed neuroblastoma, cytotoxic agents more sensitive to mutant p53 might be more effective at relapse. PMID- 11196203 TI - A three-dimensional and temporo-spatial model to study invasiveness of cancer cells by heregulin and prostaglandin E2. AB - To study the temporal expression of motile structures and protease activity during colon cancer cell invasion by heregulin-beta1 (HRG) and prostaglandin E2 (PGE2), we have developed a three-dimensional spatial model system. HRG and PGE2 each induced the formation of well-organized, three-dimensional structures with empty spaces in the center and stimulated the expression of urokinase plasminogen activator (uPA) with differential localization of membrane-bound uPA at the focal adhesion points and leading edges of the motile cells. A specific cyclooxygenase 2 inhibitor blocked the formation of three-dimensional luminal glandular structures induced by HRG but did not block those induced by PGE2. A specific antagonist of uPA receptor completely blocked the formation of these luminal glandular structures induced by PGE2 and HRG. These findings suggest that HRG mediated increased invasiveness of colon cancer cells is augmented at least in part by induction of PGE2 and uPA, and this augmentation may involve the formation of three-dimensional invasive structures via the uPA pathway. In addition, the three-dimensional model system presented here may have a wider application to screen the effects of therapeutic compounds and biomolecules on different spatial aspects of colonic biology, including cell growth, motility, invasion, survival, and apoptosis. PMID- 11196204 TI - p53 modulates base excision repair activity in a cell cycle-specific manner after genotoxic stress. AB - To elucidate the nature of the cross-talk between the p53 protein and the DNA repair machinery, we have investigated the relationship between the two throughout the cell cycle. Base excision repair (BER) was analyzed in cell cycle phase-enriched populations of lymphoid cells expressing wild-type p53. Our study yielded the following novel findings: (a) BER exhibited two distinct peaks of activity, one associated with the G0-G1 checkpoint and the second with the G2-M checkpoint; (b) although the overall BER activity was reduced after exposure of cells to 400R, there was an augmentation of the G0-G1-associated BER activity and a reduction in the G2-M-associated BER activity; and (c) modulations in these patterns of BER after genotoxic stress were found to be p53 regulated. p53 protein levels induced after gamma-irradiation were distributed evenly in the various cell cycle populations (analyzed by the PAb-248 anti-p53 monoclonal antibody). However, both the dephosphorylation of serine 376 of p53 (contained in the PAb-421 epitope) and the specific DNA binding activity, as well as apoptosis, were enhanced toward the G2-M populations. Furthermore, inactivation of wild-type p53, mediated by mutant p53 expression, abolished the alterations in the BER pattern and showed no induction of a G2-M-associated apoptosis after gamma irradiation. These results suggest that after genotoxic stress, stabilized p53 enhances the G0-G1-associated BER activity, whereas it predominantly reduces BER activity at the G2-M-enriched populations and instead induces apoptosis. After genotoxic stress, p53 functions as a modulator that determines the pattern of BER activity and apoptosis in a cell cycle-specific manner. PMID- 11196205 TI - Progesterone receptor B gene inactivation and CpG hypermethylation in human uterine endometrial cancer. AB - The expressions of two isoforms of human progesterone receptor (PR) are under the control of the two different promoters. Recent studies revealed differences between these isoforms, PRA and PRB, in their expression and function in endometrial cells. Aberrant methylation of normally unmethylated CpG islands has been associated with inactivation of several genes in human cancers. In this study, we investigated the methylation status and the expression of the two different PR isoforms, PRA and PRB, in uterine endometrial carcinoma (UEC) using methylation-specific PCR (MSP), reverse transcription-PCR (RT-PCR), the 5' rapid amplification of cDNA ends method (5'RACE), and immunohistochemical staining. The results of RT-PCR and 5'RACE suggest that only PRB is inactivated, although PRA is activated in all UEC cell lines. Treatment with a demethylating agent, 5-aza 2'-deoxycytidine, restored PRB expression in all cell lines, suggesting that inactivation of this gene is through methylation. By MSP and direct DNA sequencing, PRB was methylated, whereas PRA was unmethylated in all of the cell lines. To determine the methylation status of PRB in UEC patients, we investigated 83 cancerous and 33 normal samples. Sixty-two of 83 cancer samples had only methylated alleles of PRB, although all cancer samples had only unmethylated PRA alleles. Seventy-one of 83 cancer samples were negative for PRB expression. All 62 cancer samples that had only methylated PRB alleles were negative for PRB expression. No significant changes were observed in PRA methylation status or immunohistochemistry positivity in normal and cancer samples. To determine whether de novo methylation of PRB occurred in UEC patients, we studied 32 pairs of cancer and normal samples from the same patient. Twenty of 32 cancer samples had only methylated PRB alleles, although all 32 normal samples had only unmethylated PRB alleles. The loss of unmethylated alleles was well correlated with negativity in immunohistochemical staining for PRB. This is the first report of the selective methylation and the subsequent silencing of PRB in uterine endometrial cancer. PMID- 11196206 TI - [Classification of idiopathic macular ruptures]. AB - Based on comprehensive examinations making use of optic coherent tomography, idiopathic macular ruptures were classified (by severity) as pre-ruptures, lamellar and perforating ruptures. A 10-point scale is proposed for quantitative analysis of ruptures. Regularities in retinal changes characteristic of each type of ruptures are detected. This helps accurately evaluate the rupture, choose treatment strategy, and evaluate its results. PMID- 11196207 TI - [Clinical picture of isolated retinal vasculitis]. AB - Clinical picture of isolated retinal vasculitis (IRV) in 43 patients (25 men and 18 women) aged 22-42 years is analyzed. IRV was bilateral in 88.4% cases and involved the veins. Two forms of disease were distinguished: peripheral (in 75%) and central-peripheral (25%). Both forms were characterized by a high hemorrhagic activity, occlusion of vessels, ischemic zones and neovascularization of the retina and optic disk, but these signs were more frequent in central peripheral form of IRV. IRV is a grave disease leading to poor vision or blindness in 18% cases. The onset is poorly manifest with floating spots and blurred vision; the main symptom is vitreous hemorrhage. Visual acuity was significantly decreased in patients with occlusive IRV in comparison with those without occlusions (0.32 +/- 0.37 vs. 0.77 +/- 0.28). The earliest changes can be detected mainly in the peripheral parts of the retina. This necessitates special attention of ophthalmologist to seemingly negligible complaints of patients and thorough examination of the fundus oculi, particularly of its peripheral sections, which can be performed only on condition of adequate mydriasis. Only timely diagnosis and early pathogenetic therapy can decrease the probability of such complications as hemophthalmos, retinal neovascularization, detachment of retina, and neovascular glaucoma, and prevent disability. PMID- 11196208 TI - [Treatment of experimental corneal injuries by dioxidine and urotropin solutions]. AB - The efficiency of 1% dioxidine and 5% urotropin solutions in suppurative penetrating corneal wounds was studied in 2 experimental series on 54 rabbits. In series A toxic effects of these drugs on eyeball tissues were studied on 6 rats, in series B drug effects were studied on a model of suppurative penetrating corneal wounds. A 21-day course of therapy with these drugs (instillations and subconjunctival parabulbar injections) caused no toxic changes in ocular tissues. Therapy with 1% dioxidine and 5% urotropin accelerated clinical cure by 4-6 days in comparison with other methods of treatment. Clinical cure was observed 3-5 days sooner after combined use of both drugs in comparison with their individual application, during during combined use their antibacterial effect was synergistic. Hence, a combination of 1% dioxidine and 5% urotropin solutions is an effective method for treating suppurative penetrating wounds of the cornea. PMID- 11196209 TI - [Comparative study of tears protein composition in patients after photorefractive keratectomy and laser specialized keratomileusis]. AB - Changes in the protein spectrum of the lacrimal fluid, resultant from refraction ocular surgery (photorefraction keratectomy, PRK, and laser specialized keratomileusis, LASIK) were evaluated. Lacrimal fluid was collected before operation and in various terms after it in 28 patients (48 eyes) subjected to PRK and in 34 patients (59 eyes) subjected to LASIK. Biochemical analysis of the lacrimal fluid was performed on a mass spectrometer. After PRK the greatest changes in the protein spectrum occurred immediately after the operation before reepithelialization. Changes after LASIK were negligible. Refraction laser operations cause changes in the protein composition of tears, LASIK being more physiological than PRK from viewpoint of intactness of the protein composition of tears. PMID- 11196210 TI - [Evaluation of various methods effectiveness for aphakia correction in patients with myopic refraction and glaucoma]. AB - The efficiency of various methods for correcting postoperative aphakia was evaluated in 113 patients (118 eyes) with medium and high myopia and glaucoma. In group 1 (44 eyes) extraocular correction of aphakia was planned after cataract extraction, in group 2 (33 eyes) intraocular lenses were implanted, in group 3 (21 eyes) combined interventions were performed (cataract extraction with antiglaucoma component), and in group 4 (20 eyes) cataract extraction was performed simultaneously with sinusotrabeculectomy and intraocular correction of aphakia. The number of patients with visual acuity higher than 0.1 was significantly more in groups 2 and 4 after implantation of intraocular lenses than in groups 1 and 3, who needed extraocular correction of aphakia: 59.1% in group 1, 42.9% in group 3, 78.8% in group 2, and 60% in group 4. Intraocular correction of aphakia in patients with glaucoma and myopia helps attain the maximum possible visual acuity even in patients with far-advanced stages of the disease with residual visual field. Individual approach to estimation of optic force of implanted intraocular lens helps reduce the myopic refraction of the operated eye. PMID- 11196211 TI - [Cosmetic results of posttraumatic eyeball subatrophy surgical treatment using "alloplant" biomaterials with subsequent use of prostheses]. AB - A complex of surgical operations making use of Alloplant biomaterials, performed in 47 patients with initial posttraumatic subatrophy and 79 patients with well developed and far advanced stages of this condition, helped preserve the eye as anatomical organ in 97.5% patients, with enlargement of the eyeball in two-thirds of patients and stabilization in one-third. Optic reconstructive operations were later performed and visual acuity improved in patients with the initial stage of subatrophy. Use of allotransplant for eyeball bandage in order to create a carcass for the sclera helped conceal the cicatricial deformation of the sclera and repair the shape and volume of the eyeball in patients with initial subatrophy, due to which a good cosmetic result was attained. In well-developed and far advanced subatrophy use of biomaterial for bandage created optimal conditions for thin-wall cosmetic prostheses, ruled out the irritating effect of the prosthesis in cases when corneal sensitivity was retained and/or there were coarse corneaoscleral cicatrices, and thus extended the indications for cosmetic prostheses of subatrophic eyes. PMID- 11196212 TI - [Indications, terms and classification of reconstructive interventions based on penetrating keratoplasty with implantation of posterior chamber intraocular lens]. AB - Based on analysis of 750 reconstructive operations on the anterior segment of the eye, the authors classify simultaneous reconstructive interventions based on perforating keratoplasty with implantation of posterior chamber intraocular lens (IOL). Indications, terms, and technological features of such operations are defined with due consideration for the etiology of involvement of the anterior segment of the eye, corneal status, presence of the lens, and intactness of the lenticular posterior capsule. Disk posterior chamber IOLs with intracapsular fixation are preferred (in case of an intact capsule sac, with suturing to the posterior surface of the cornea) in the absence of the posterior capsule of the lens. As a result of surgery, improvement of visual acuity by 0.04-0.8 was attained in 720 patients. PMID- 11196213 TI - [Experience of garasone use in surgical practice]. AB - The efficiency of garasone (Schering-Plau) in preoperative and postoperative treatment was evaluated in 50 patients. Controls (48 pts) were treated by combinations of antibiotics (0.25% levomycetin and 20% sodium sulfacyl solutions) and antiinflammatory drugs (0.1% dexamethasone and maxidex). The postoperative inflammatory reaction ceased much sooner in the patients treated with garasone than in the controls. Conjunctival edema, corneal edema, and descemetitis completely disappeared on days 4-5 after the operation in the study group and only on day 6 in the control. Higher efficiency of garasone can be attributed to the advantages of its components: wide-spectrum gentamicin and its high bioavailability for the eyeball tissues and an effective steroid betamethasone. One more advantage of garasone is that it is convenient to use (a single flask, no need in repeated instillations). The results recommend garasone for wide use for prevention and treatment of postoperative inflammatory diseases of the eyes. PMID- 11196214 TI - [Ophthalmodynamography in studies of ocular hemodynamics in normal subjects of different age with different arterial pressure]. AB - Computer-aided ophthalmodynamographer for studies of hemodynamics in the orbital artery has been elaborated at research and production firm All-Russian Institute of Medical Engineering--Optimed. A total of 292 healthy subjects (542 eyes) aged 28-77 years with systolic pressure 100-170 mm Hg were examined. Main hemodynamic parameters in the orbital artery were determined: systolic, diastolic, mean ophthalmic, perfusion pressure, and systolic increment in pulse volume. Ocular hemodynamic parameters, except systolic increment in pulse volume, directly depend on systemic arterial pressure but not on age. Normal parameters of systolic, diastolic, mean ophthalmic, and perfusion pressure in the orbital artery at certain levels of systemic arterial pressure were determined. PMID- 11196215 TI - [Efficiency of removing a transparent lens in high myopia]. AB - Results of removal of a transparent lens in high myopia are analyzed. The operation was performed in two stages according to V. S. Belyaev and T. S. Ilyina. The second stage of the operation (lens extraction) was performed by the extracapsular method, which prevented vitreous prolapse into the anterior chamber in all cases and ruled out the possibility of detachment of the posterior plate of the vitreous and retina. Simple technique of the operation, good remote results, no need in expensive instruments or equipment recommend this operation for any ophthalmological department performing extracapsular cataract extractions. PMID- 11196216 TI - [Immunopathological process in retina during development of diabetic retinopathy]. PMID- 11196217 TI - [Remote results of high myopia surgical correction by tunnel keratoplasty ]. AB - Remote results evidence high refraction efficiency of tunnel keratoplasty, stable results being observed for up to 15 years. A total of 104 operations (58 patients) were analyzed for a period of observation of more than 10 years. The patients' ages varied from 17 to 52 years, there were 34 women and 24 men. The main advantage of interlamellar refraction meridional keratoplasty is easiness of operation. At present it is the operation of choice for dosed reduction of eye refraction aimed at correction of high myopia and astigmatism. The possibility of correcting residual myopia after keratotomy and repair of refraction abnormalities resultant from perforating keratoplasty is particularly interesting. The possibility of regulating the corrective effect in remote periods by replacing the implants also deserves attention. Hence, low traumatism, high efficiency, and stability of the refraction effect once more confirm our recommendation to use tunnel keratoplasty in clinical practice. PMID- 11196218 TI - [Potentialities of conservative and surgical treatment of patients with congenital microphthalmia and anophthalmia]. AB - Congenital anophthalmia and microphthalmia were responsible for 1.7-1.8% cases of all cases treated at laboratory of plastic surgery and ocular prostheses. Clinical picture of the condition is described. The philosophy of rehabilitation of patients with congenital anophthalmia and microphthalmia is as follows: 1) no operations during the first years of life; 2) early staged fitting with prostheses; 3) surgical treatment in older age, when the resources of conservative extension of the cavity are exhausted. The authors emphasize that active conservative treatment should be preferred. Method for nonsurgical extension of the conjunctival cavity by staged insertion of prostheses is described. Positive and negative aspects of surgical treatments are discussed. The authors emphasize that surgical activity in early age is extremely harmful. Results of surgical treatment of 27 patients are presented. The patients were divided into 2 groups differing by the tasks of surgery: repair of consequences of previous operations (59.2% cases) and typical correction of the eye lids (40.8%). Clinical examples are offered. PMID- 11196219 TI - Towards an alternative approach to personhood in the end of life questions. AB - Within the Western bioethical framework, we make a distinction between two dominant interpretations of the meaning of moral personhood: the naturalist and the humanist one. While both interpretations of moral personhood claim to promote individual autonomy and rights, they end up with very different normative views on the practical and legal measures needed to realize these values in every day life. Particularly when we talk about the end of life issues it appears that in general the arguments for euthanasia are drawn from the naturalist interpretation of moral personhood while the arguments against euthanasia, for their part, are derived from the idealist and/or humanist understanding of the same concept. This article focuses on examining the metaphysical assumptions and internal contradiction found behind the opposing arguments presented by two prominent philosophers of these two traditions: Peter Singer and Ludger Honnefelder. The author claims that neither side of the debate succeeds in defending its normative position without reconsidering how to take the social aspects of moral personhood into account. The author holds that, despite our need to set individual's decision making into social context, the current communitarian narrative concept of personhood fails to offer a convincing alternative. Instead of merely trying to replace psychological and atomistic view of personhood with a collective understanding of an individual's moral identity, we need to discuss the normative relation between the concept of 'moral personhood' and the demand for respect of individual autonomy in Western bioethics within a wider philosophical perspective. PMID- 11196220 TI - 'Watching' medicine: do bioethicists respect patients' privacy? AB - Agich has identified 'watching' --the formal or informal observation of the medical setting-- as one of the four main roles of the clinical bioethicist. By an analysis of a case study involving a bioethics student who engaged in watching at an HIV/AIDS clinic as part of his training, I raise questions about the ethical justification of watching. I argue that the invasion of privacy that watching entails makes the activity unacceptable unless the watcher has received prior consent from the patients who are being observed. I conclude that, even though it is important for bioethics students to understand the complexities of actual medical practice, watching should play a prominent role in bioethics education only if the privacy problems in it can be resolved. PMID- 11196221 TI - The biomedical disciplines and the structure of biomedical and clinical knowledge. AB - The relation between biomedical knowledge and clinical knowledge is discussed by comparing their respective structures. The knowledge of a disease as a biological phenomenon is constructed by the interaction of facts and theories from the main biomedical disciplines: epidemiology, diagnostics, clinical trial, therapy development and pathogenesis. Although these facts and theories are based on probabilities and extrapolations, the interaction provides a reliable and coherent structure, comparable to a Kuhnian paradigma. In the structure of clinical knowledge, i.e. knowledge of the patient with the disease, not only biomedical knowledge contributes to the structure but also economic and social relations, ethics and personal experience. However, the interaction between each of the participating "knowledges" in clinical knowledge is not based on mutual dependency and accumulation of different arguments from each, as in biomedical knowledge, but on competition and partial exclusion. Therefore, the structure of biomedical knowledge is different from that of clinical knowledge. This difference is used as the basis for a discussion in which the place of technology, evidence-based medicine and the gap between scientific and clinical knowledge are evaluated. PMID- 11196222 TI - Dualism and its importance for medicine. AB - Cartesian dualism has been viewed by medical theorists to be one of the chief causes of a reductionist/mechanistic treatment of the patient. Although I aver that Cartesian dualism is one culprit for the misapprehension of the genuine treatment of patients in terms of both mind and body, I argue that interactive dualism which stresses the interaction of mind and body is essential to treat patients with dignity and compassion. Thus, adequate medical care that is humanistic in nature is difficult (if not impossible) to achieve without physicians adhering to a dualistic framework in which the body and person is treated during illness. PMID- 11196223 TI - Generalised chronic musculoskeletal pain as a rational reaction to a life situation? AB - While the biomedical model is still the leading paradigm within modern medicine and health care, and people with generalised chronic musculoskeletal pain are frequent users of health care services, their diagnoses are rated as having the lowest prestige among health care personnel. An epistemological framework for understanding relations between body, emotions, mind and meaning is presented. An approach based on a phenomenological epistemology is discussed as a supplement to actions based on the biomedical model. Within the phenomenological frame of understanding, the body is viewed as a subject and carrier of meaning, and therefore chronic pain can be interpreted as a rational reaction to the totality of a person's life situation. Search for possible hidden individual meanings in painful muscles presupposes meeting health personnel who view the person within a holistic frame of reference. PMID- 11196224 TI - Dying in America. PMID- 11196225 TI - [Proposal for a classification of Class II Division 1: contribution of Delaire's analysis]. AB - Class II division 1 dental malocclusions are present in various forms depending on the site, direction and degree of discrepancy between the arches. The ability to recognize the origin of the malocclusion is essential to decide how, and when it is necessary to treat. In this study, the Delaire's analysis was performed for 111 individuals with a Class II division I malocclusion; a classification of these cases is proposed, according to the presence or the absence of a skeletal discrepancy. In 87% of the cases, a Class II division 1 dental malocclusion was associated with a Class II skeletal discrepancy (50% maxillary prognathism, 23.5% normal maxillary relationship and 13.5% maxillary retrognathism). The lines of the cranial base, the shape and size of the mandible varied considerably. In only 6% of cases, the dental malocclusion was associated with a skeletal Class I relationship, and in 7% of cases with a Class III relationship: it was often related to retruded mandibular teeth. It was shown that Class II division 1 dental malocclusions may result from differing causes: therefore, the identification of their etiology seems essential to provide the best possible treatment, at the right period in time. PMID- 11196226 TI - [Body posture and craniofacial morphology]. AB - The body posture has been studied according to the craniofacial morphology. A cephalometric analysis (lateral cephalometric radiographs) and a stabilometric recording of the posture with a vertical force platform have been done for 45 individuals: 17 boys and 28 girls aged 9 to 16 years. Cephalometric sagittal and transverse variables show no correlation with the sagittal position of the center of foot pressure. It seems that mild to moderate dentofacial deformities do not reflect on the posture of the body as a whole. PMID- 11196227 TI - [Influence of saggital inclination of the teeth and the orientation of the occlusal plane on mesial drift in the dental arch]. AB - As a rule, the occlusal plane in man is not flat but curved in the three dimensions. This curved organization is related to a specific phenomena: the continuity of the dental arch without diastema. The Page's proposal of the tangent law explains the sagittal organization of the mandibular teeth by geometrical analyses. A cephalometric analysis of 485 subjects, in natural dentition, is the basis for the present statistical study of the mandibular teeth sagittal inclination, related to the direction of the tangent. Mandibular incisors follow the tangent law, but the long axis of the posterior mandibular teeth exhibits a postero-anterior and progressive differential angle with the direction of the tangent: 15 degrees, 20 degrees, 25 degrees, 28 degrees. The differential angle with the direction of vertical strength during closure movement generates an horizontal strength component, with a tendency to create a forward tooth movement. This horizontal component of force is tightening the proximal contacts, maintaining the continuity of the dental arch: it also originates the mesial "drift" and mandibular incisor crowding. PMID- 11196228 TI - [A device for mandibular advancement in respiratory disorders of sleep. Clinical study]. AB - This study describes the technical steps for the making of a mandibular advancement device for sleep disordered patients (apnea index < 10). In a second part of the study, a group of 21 patients with sleep disordered breathing treated successfully with a mandibular advancement device is compared to a homologous control group. The experimental group showed cephalometric characteristics approaching those seen in patients with sleep apnea syndrome. The mandibular advancement device moved the mandibule forward (SNB angle increases by 1.7 degrees) and downward (mandibular plane angle increases by 3 degrees, which can be related to the 7.4 mm anterior vertical height increase). The hyoid bone adopted a more distant position from the cervical vertebrae. Important individual variations were seen among the patients for the optimal repositioning of the mandible. PMID- 11196229 TI - [Functional and esthetic rhinoplasty in orthognathic surgery]. AB - The author presents a surgical rhinoplasty, aiming at functional and aesthetic purposes, in dentofacial orthopedics. PMID- 11196230 TI - [Excellence in orthodontics. Interview by M. G. Choukroun and O. Sorel]. AB - "Excellence is not an act, it is a daily exercise", is a sentence quoted by B. Zachrisson and is the cornerstone of his approach. He explains how, by a careful inspection and an analysis of the facial bone structure, using the patient's movement, he can establish a diagnosis and set the treatment's objectives. He defines the key points of a balanced smile, the rules and guidelines for enamel reproximation, the methods of bonding and the rules governing the stability of orthodontic treatments. PMID- 11196231 TI - [Growth and choices in orthopedic or orthodontic therapy]. AB - Although the clinical aspects of the skeletal Class II can be numerous, in most cases an insufficient sagittal development of the mandible can be identified. Besides the functional disorder caused by the sagittal skeletal problem, the aesthetic appearance is damaged. To provide an efficient orthodontic or orthopedic treatment, the practitioner must consider this aesthetic prejudice, while correcting the functional disorder. One of the main goal when correcting skeletal Class II relationships is to improve the sagittal development of the mandibular growth. The sagittal impact is greater for the horizontal growth and will improve the aesthetic appearance. In addition, the treatment will be easier, shorter and therefore less traumatic because of the spontaneously natural self correction. Finally, the correction will be more stable because the functions such as breathing and swallowing will be easily rehabilitated. To obtain convenient aesthetic and functional corrections of skeletal Class II relationships, four essential rules must be taken care of: finding the best therapeutic choice, choosing the best moment to start treatment, initiating an efficient unlocking, providing an overall treatment. PMID- 11196232 TI - [Trends in orthodontic biomaterials: metals and ceramics]. AB - While the beginning of orthodontics was marked by an acute scarcity in materials, the modern clinician has to face a large array of devices made of metals, plastics, ceramics and combinations thereof. Each of these materials have been developed for other purposes than orthodontics, and then transplanted "as is" in a field which has its own demands. During the years, theses devices, as well as the materials these are made of, have been modified most of time to the benefit of both the patient and the clinician, and some time to that of the manufacturer who has tried to save, or bypass limiting patients. Among the latter are the harder, but less corrosion resistant steels, the efficient but corrosion prone brazing, the inexpensive but weaker molded attachments, the aesthetic but fragile ceramics. Understanding the trends and basics of materials science should help the clinician to avoid being sued iatrogenic inflicted affections. PMID- 11196233 TI - [Comparative study of mandibular growth and rotation in two sample groups treated according to the "Distal Active Concept" or the Edgewise technique]. AB - The "Distal Active Concept" therapy, favours an immediate repositioning of the mandible and introduces new therapeutic sequences which allow an easy correction of the Class II molar relationship, enhancing the mandibular growth simultaneously. The "Distal Active Concept" therapy is a combined treatment which induces the correction of the Class II malocclusion without extractions and without headgear. The dento-alveolar unit is used as a functional matrix to free, then enhance the mandibular growth and induce its counter-clockwise rotation. 35 patients treated with the "Distal Active Concept" therapy are compared to 33 patients, treated with the extraction of four bicuspids and in Edgewise therapy, in order to visualize the mandibular growth and the counterbalancing rotation described by Dibbets. PMID- 11196234 TI - [Synthesis and evaluation of the clinical approach to growth]. AB - A critical reflection based on literature is presented to the lectures given at the symposium "A clinical approach to growth" at the 73rd Reunion Scientifique of the Societe Francaise d'Orthopedie Dento-Faciale in Deauville, France, on may 13th, 2000. Uncertainty is expressed about the long-term effects on the growth pattern after early surgery in children. It is apparent that conventional dentofacial orthopedics have a limited long-term effect on the growth pattern. Surgical as well as non-surgical (orthopedic) approaches are plagued by complications and relapse. The need for unbiased clinical research and standardized, complete documentation and analysis--also on how/why clinical decisions were taken--seems of utmost importance for a balanced future development of conventional and newly introduced techniques. PMID- 11196235 TI - [Xenotransplantation: utopia or clinical reality?]. AB - Xenotransplantation, i.e. the transplantation of organs (tissues, cells) from animals into humans has been a major question in medicine for many years. Based on the ever increasing shortage of suitable donor organs, the research of xenotransplantation grew more intensive than ever before. The problems associated with xenotransplantation can be divided into four categories: i./ immunological, ii./ physiological, iii./ infectious-microbiological, iv./ ethical. In this study the author attempts to summarize the possibilities of xenotransplantation, the problems associated with it, and their possible solutions. PMID- 11196236 TI - [Long-chain polyunsaturated fatty acids in the early development of the human nervous system]. AB - The role of long-chain polyunsaturated fatty acids (LCPUFA) in the early development of the human nervous system was put forward by the better cognitive development observed in breast-fed than in formula fed infants in parallel with the presence of LCPUFA in human milk but not in formula. The role of LCPUFA in early human neurodevelopment can be investigated by comparing data obtained in formula fed infants randomly assigned to receive formula with or without LCPUFA. Investigations in preterm infants indicate that the presence of LCPUFA in the formula offers benefits for the early postnatal development of visual and cognitive functions. The unequivocal results obtained in preterm infants led to the recommendation of LCPUFA supplementation to formulae for preterm infants. In several studies in full-term infants, enhanced dietary intake of LCPUFA was accompanied with better visual acuity and better results in various cognitive tests. However, other studies did not show visual or cognitive differences between full-term infants fed formula with or without LCPUFA. It is a question under current debate whether supplementation of LCPUFA to formulae for full-term infants is required to lessen the difference between the intellectual development of breast-fed and formula fed infants. PMID- 11196238 TI - [Meta-analysis of therapeutic and preventive clinical trials]. AB - The paper surveyes the principles and the models of meta-analysis and gives the basic statistical formulae. For evaluation of data of clinical trials two illustrative examples are presented: 1. evaluation of association and homogeneity in fixed and random models of the common standardized treatment effects measured by continuous variable with known sample sizes, means and standard deviations; 2. evaluation of association and homogeneity in fixed model of: the common InRelative-Risk and Risk-Difference ot treatment effects determined by dichotomous variable categorized in 2 x 2 tables and completed with Stouffer and Fisher methods combining z and p values of percentage differences of the treatment effects. It is demonstrated that the presented two illustrative examples, as models of meta-analysis provide objective statistical methods for data summarization of clinical trials. Evidence based medicine applies also the methods of meta-analysis. PMID- 11196237 TI - [Serum eosinophil cationic protein (sECP) level after cow's milk challenge test in allergic children]. AB - The eosinophil cationic protein (ECP) level in the sera is higher in allergic diseases. The change of the ECP level in the sera of patients with cow milk allergy was examined during the cow's milk challenge test after a long cow's milk free diet period. The sECP level of 35 milk sensitive patients was determined by a fluoroimmunoassay (Pharmacia CAP System ECP FEIA) before the milk challenge test, as well as 2 and 24 hours after it. The average age of the patients was 16 (6-49) months. The basic sECP level of cow's milk allergic patients was significantly higher (12.2 micrograms/l vs. 7.0 micrograms/l, p < 0.05) than that of the control group (n = 20). The sECP level significantly decreased 2 hours after the milk challenge test (12.2 micrograms/l vs. 9.2 micrograms/l, p = 0.01), 24 hours after the challenge it was again on the basic level (11.2 micrograms/l, p = 0.26). Out of the 35 allergic children ten had positive clinical reactions after the milk challenge test (positive group), while 25 had no reaction after it (negative group). Comparing the sECP level of these two groups, no significant difference was found in the sECP level either before the milk challenge test or after it. The significant decrease of the sECP level 2 hours after the beginning of milk challenge test might be explained by the fact that this toxic protein is secreted into the bowel. PMID- 11196239 TI - [Hypophosphatemic oncogenic osteomalacia]. AB - The first case of oncogen osteomalacia in Hungary is reported, to draw the attention of the medical profession to it and to present the new data about its pathomechanism. Pathological hip fracture caused by hypophosphataemic osteomalacia due to isolated renal phosphate wasting was found in a previously healthy 19 years old sportsman. In spite of daily 1.5 micrograms calcitriol treatment and phosphate supplementation, hypophosphataemia persisted for 13 years and he needed regular indometacin medication for his bone pain. During that time an 1.5 cm gingival tumour was found and radically removed. The serum phosphate level returned to normal in a few hours after the operation (preoperative 0.51, after 2, 4 and 8 hours 0.61, 0.68 and 0.79 mmol/l respectively), and remained normal without calcitriol. The histological examination showed epulis with fibroblast and vascular cell proliferation, which has never been previously reported in connection with oncogenic osteomalacia. The pain resolved after 3 months and the bone density became normal in one year. Oncogenic osteomalacia must be considered in every case presenting with atypical hypophosphataemic osteomalacia. Careful dental examination is needed also in the course of search for the underlying tumour. Every tumour-like growth, even the common epulis, has to be operated radically and serum phosphate monitored in the postoperative period in all such cases. PMID- 11196240 TI - [Faulty calculations of drug costs by the Hospital Association]. PMID- 11196241 TI - [Assessing the extent of alcohol consumption]. PMID- 11196242 TI - [Zoltan Vamossy, Editor of the Medical Weekly and Antal Tiszamarti]. PMID- 11196243 TI - Bibliography. Current world literature. Leukemia. PMID- 11196244 TI - Bibliography. Current world literature. Endocrine tumors. PMID- 11196245 TI - Bibliography. Current world literature. Cancer biology. PMID- 11196246 TI - Enuresis--background and treatment. AB - Nocturnal urinary continence is dependent on 3 factors: 1) nocturnal urine production, 2) nocturnal bladder function and 3) sleep and arousal mechanisms. Any child will suffer from nocturnal enuresis if more urine is produced than can be contained in the bladder or if the detrusor is hyperactive, provided that he or she is not awakened by the imminent bladder contraction. Urine production is regulated by fluid intake and several interrelated renal, hormonal and neural factors, foremost of which are vasopressin, renin, angiotensin and the sympathetic nervous system. Detrusor function is governed by the autonomic nervous system which under ideal conditions is under central nervous control. Arousal from sleep is dependent on the reticular activating system, a diffuse neural network that translates sensory input into arousal stimuli via brain stem noradrenergic neurons. Disturbances in nocturnal urine production, bladder function and arousal mechanisms have all been firmly implicated as pathogenetic factors in nocturnal enuresis. The group of enuretic children are, however, pathogenetically heterogeneous, and two main types can be discerned: 1) Diuresis dependent enuresis - these children void because of excessive nocturnal urine production and impaired arousal mechanisms. 2) Detrusor-dependent enuresis - these children void because of nocturnal detrusor hyperactivity and impaired arousal mechanisms. The main clinical difference between the two groups is that desmopressin is usually effective in the former but not in the latter. There are two first-line therapies in nocturnal enuresis: the enuresis alarm and desmopressin medication. Promising second-line treatments include anticholinergic drugs, urotherapy and treatment of occult constipation. PMID- 11196247 TI - Sex offender testimony: junk science or unethical testimony? PMID- 11196248 TI - Illegal behaviors in problem gambling: analysis of data from a gambling helpline. AB - Problem gambling behaviors, particularly the most severe form, which is pathological gambling (PG), represent an emerging public health problem. Compared with the general population, individuals with problem gambling are more likely to have reports of legal issues, including commission of crimes, arrest, and incarceration. The goal of the present study is to examine the characteristics of individuals seeking help for gambling problems with regard to reports of illegal behavior secondary to gambling. Individuals with gambling problems were identified through use of a 24-hour gambling helpline, and information regarding the identified problem gambler was investigated with respect to reported presence or absence of gambling-related illegal behaviors. Identified gamblers with reported gambling-related illegal behaviors compared with those without such behaviors appeared to experience more severe gambling-related problems. Despite being on average younger, gamblers with acknowledged gambling-related illegal behaviors were more likely to have reports of having problems with multiple forms of gambling, debts to acquaintances, been suicidal secondary to gambling, used alcohol or drugs excessively, and received mental health treatment. Secondary analyses of the subgroup of gamblers with gambling-related illegal behaviors revealed that those with reports of arrest or incarceration secondary to gambling compared with those with gambling-related illegal behaviors but without arrest or incarceration secondary to gambling were more likely to have features similar to those described for individuals with antisocial personality disorder (ASPD). That is, the gambler with reported arrest or incarceration secondary to gambling was more likely to be male, unemployed, single, and have reports of problems with excessive drug or alcohol use. In contrast, the gamblers acknowledging gambling related illegal behaviors but not arrest or incarceration secondary to gambling were predominantly female and more likely to have reports of problems with non strategic forms of gambling (e.g., slot machine), owing money to legitimate sources of borrowing, having filed for bankruptcy, and having family problems related to gambling. The findings indicate: (1) individuals with reported legal problems secondary to gambling represent a more ill subpopulation of problem gamblers; and (2) there exist separate subgroups of gamblers with gambling related illegal behaviors (i.e., those with or without reported arrest or incarceration secondary to gambling) with strikingly different characteristics and possibly different treatment needs. The results of the present study highlight the importance of the identification and treatment of individuals with gambling problems with respect to legal issues. PMID- 11196249 TI - Commentary: types, lotteries, and substance abuse among problem gamblers. PMID- 11196250 TI - All God's children: religion, divorce, and child custody. AB - Many young Americans, married and marriageable, are turning to more traditional or fundamentalist religions. Religiosity and ultra-strict morality often leads to attitudes that alter decision-making in marriage, divorce, and the disposition of the children of divorce. Judgmental pastoral counseling may affect these decisions even more. This paper discusses these issues, emphasizing the need for forensic psychiatrists involved in the custody arena to be aware of the religious, spiritual, irreligious, or even anti-religious feelings of the battling partners. It also presents detailed information about the four major American religions (Roman Catholicism, traditional Judaism, Mormonism, and Islam) that have specific doctrine, protocols, or customs affecting decisions in marriage, divorce, and child custody and visitation. This information is presented from the viewpoint of a child advocate. Mental health experts consulting in child custody must understand the backgrounds of the battling parents, including the religious pressures that well may adversely affect their interspousal disputes, particularly those over child custody. The experts must also recognize the attitudes of the religious communities in which the custodial parent may reside after divorce. Those attitudes may be rejecting of the children as well as of the divorced parent(s). Mental health experts may have a better chance to reach agreement between the battling parents if the experts reverse the historic reluctance of psychiatrists to evaluate and discuss the religious feelings and beliefs of their forensic evaluatees. PMID- 11196251 TI - Commentary: religiously enlightened consultation for child custody disputes. PMID- 11196252 TI - Survey of forensic psychiatrists on evaluation and treatment of prisoners on death row. AB - Psychiatrists have debated their role in evaluating prisoners accused of capital crimes and in treating prisoners on death row when restoration of competence would result in execution. Despite debate, there are no previous surveys of psychiatrists' opinions on this issue. We sent an anonymous questionnaire to all board-certified forensic psychiatrists in the United States. Of the 456 forensic psychiatrists identified, 290 (64%) returned the survey. Most respondents supported a role, in at least some cases, for psychiatric evaluation of prisoners accused of capital crimes. Respondents were divided on whether or not psychiatrists should treat incompetent death row prisoners if restoration of competence would result in execution. Attitudes about the ethical acceptability of capital punishment were associated with views about the psychiatrists' role but were not determinative in every case. PMID- 11196253 TI - Licensure requirements for out-of-state forensic examinations. AB - Forensic clinicians, including psychiatrists, are sometimes asked to perform solely forensic (e.g., court- or litigation-related) assessments or interviews outside states in which they are licensed. A short survey was sent to all U.S. state medical licensing agencies asking whether or not a psychiatrist licensed in another state must also be licensed in the surveyed state before performing a purely forensic interview or examination. Of the 45 states responding, 21 said that no additional "local" license would be required; 6 gave unclear responses; and 18 said a local license would generally be required. At least 7 of the 18 states that generally require a local license accept unlicensed out-of-state physicians when they are requested by or consulting to an in-state physician. The state's definition of "medical practice" figured heavily in many responses. No pattern of state size (area), population density, or geographic location was discerned. The materials received, comments by board staff and attorneys, and interpretations or assumptions by the author are not to be construed as "official" for any state. PMID- 11196254 TI - Actuarial risk assessment models: a review of critical issues related to violence and sex-offender recidivism assessments. AB - Risk assessment in the area of identification of violence has been dichotomized by several prominent researchers as the "clinical approach" versus the "actuarial method". The proponents of the actuarial approach argue for actuarially derived decisions to replace existing clinical practice. The actuarial method requires no clinical input, just a translation of the relevant material from the records to calculate the risk score. A risk appraisal approach based upon a sole actuarial method raises several questions: those of public safety, peer-accepted standards of practice, liability issues, and concordance with evidence-based medicine practice. We conclude that the sole actuarial approach fails to satisfy these critical issues. PMID- 11196255 TI - "Telling tales out of court": a pilot study of experts' disclosures about opposing experts. AB - A pilot questionnaire surveyed forensic psychiatrists and psychologists about information they would feel it appropriate to disclose to their retaining attorneys about an opposing expert witness. A spectrum of hypothetical disclosures was offered, varying in their relevance to the case at hand and in their degree of "public" versus "personal" information. Respondents agreed significantly that "public" information could be disclosed to one's attorney, but responses about disclosing "personal" information varied widely. The findings and their implications are briefly discussed. PMID- 11196256 TI - Criminal responsibility, diminished capacity, and the gay panic defense. PMID- 11196257 TI - Canadian landmark case: L.C. and the Attorney General for Alberta v. Brian Joseph Mills. PMID- 11196258 TI - Troxel, et vir, Petitioners v. Granville: grandparents' rights or parental autonomy? PMID- 11196259 TI - Dangerous severe personality disorder: extension of the use of civil commitment in the United Kingdom. PMID- 11196260 TI - Mental health court: promises and limitations. PMID- 11196261 TI - Re: "Terrorist on trial: the context of political crime". PMID- 11196262 TI - Disease outcome may be predicted by molecular detection of minimal residual disease in bone marrow in advanced neuroblastoma: a pilot study. AB - PURPOSE: This pilot study focussed on whether sequential molecular detection of minimal residual disease (MRD) in bone marrow (BM) could predict the outcome of patients with advanced neuroblastoma. PATIENTS AND METHODS: Bone marrow samples from 21 patients older than age 12 months with stage IV neuroblastoma were sequentially examined for tumor cell contamination by detecting tyrosine hydroxylase (TH) messenger ribonucleic acid (mRNA) using reverse transcription polymerase chain reaction (RT-PCR). Twenty patients received myeloablative therapy with hematopoietic stem cell transplantation after achieving complete remission. RESULTS: All BM samples of patients except that of one patient was cytologically positive for neuroblastoma cells at diagnosis, and they became negative for neuroblastoma cells within 3 months by cytologic examination. By RT PCR analysis, BM samples of all patients were positive for TH mRNA at diagnosis, and samples of 19 patients became negative for TH mRNA 1 to 13 months after the start of chemotherapy. Six patients whose BM samples became negative for TH mRNA within 4 months after the start of chemotherapy remained alive without evidence of disease (median 76 mos, range 36-91). In contrast, out of 15 patients whose BM samples remained positive, 10 patients had relapse develop and 9 patients died from disease (median 15 mos, range 10-25). There was a statistically significant difference in disease-free survival between the two groups (P < 0.05). CONCLUSION: Persistence of MRD in BM may predict poor prognosis in advanced neuroblastoma. PMID- 11196263 TI - Posttransplant lymphoproliferative disease in children: correlation of histology to clinical behavior. AB - PURPOSE: To determine whether the morphologic features of posttransplant lymphoproliferative disease (PTLD) correlated to a response to therapy. PATIENTS AND METHODS: We reviewed our experience with PTLD in the pediatric population. We identified 32 patients with a total of 36 episodes of PTLD. The diagnosis was confirmed by tissue examination and classified according to the degree of monomorphic features of the lesion. Thirty-four of 36 episodes were managed with immunosuppression reduction, and the patients were assessed for their response to this strategy. Chemotherapy was used to treat 10 of 15 patients who had progressive disease, and their subsequent course was also analyzed. RESULTS: Sixteen of 17 (94%) patients with polymorphic morphology responded to immunosuppression reduction compared with only 5 of 17 (29%) patients with monomorphic features (P < 0.001). All of the patients with progressive disease who did not receive additional therapy died. Standard chemotherapy regimens for lymphoma were administered to 10 patients with progressive disease, with a high response rate (90%), durable remissions, and acceptable toxicity. CONCLUSIONS: We conclude that the morphologic characteristics of PTLD provide information to potentially help guide treatment strategies in the management of this disease. Standard chemotherapy regimens for malignant lymphoma appear to be a viable treatment option for patients with progressive disease, although further investigation is needed. PMID- 11196264 TI - Impact of pharmacy practices on the cost of colony-stimulating factor use in pediatric stem cell transplantation: an institution-based analysis. AB - PURPOSE: An evaluation of colony-stimulating factor (CSF) use in pediatric stem cell transplantation (SCT) was conducted to identify potential cost-efficiencies while preserving institutional standards of patient care. METHODS: Clinical and pharmacy records of the 55 SCTs performed during fiscal year 1995 were reviewed. Material costs per vial and per microgram, exclusive of preparation or overhead costs, were used. The best costing strategy was defined as the least expensive stocking and dispensing practice to deliver the drug actually used during the study period. RESULTS: CSFs were used in 35 of 55 transplants; 68% of usage was protocol-mandated to enhance engraftment; the remainder was associated with life threatening complications of SCT. All use was consistent with published evidence based guidelines. Changes in stocking and dispensing practices would result in an overall annual savings of $48,162 (fiscal year 1995 dollars), a 39% decrease in cost without a change in clinical application. CONCLUSIONS: Our analysis demonstrates that stocking and dispensing practices place significant fiscal burden in the care of pediatric-aged patients and must be carefully considered. This analysis presents a model for evaluating all components of drug cost from a global perspective, highlighting a need for examination of pharmacy and manufacturing as well as clinical practices. PMID- 11196265 TI - Myelopoietic growth factors after stem cell transplantation: does it pay. PMID- 11196266 TI - Abundance of apoptotic neoplastic cells in diagnostic biopsy samples is not a prognostic factor in childhood primitive neuroectodermal tumors of the central nervous system. AB - PURPOSE: To assess if the abundance of apoptotic tumor cells is an independent prognostic factor in primitive neuroectodermal tumors (PNET) of the central nervous system. PATIENTS AND METHODS: Formalin-fixed paraffin-embedded tumor tissue sections from 78 clinically well-characterized children with PNET were evaluated by terminal deoxytransferase-mediated deoxyuridinie-5'-triphosphate (dUTP) nick-end labeling (TUNEL). Apoptotic indices (AI) were determined by counting TUNEL-positive tumor cells either in the highest staining region (AI hot spot) or in at least 15 randomly chosen fields (AI random). The AI hot spot and AI random were then correlated with clinical variables and survival outcome. RESULTS: AI hot spot (median 0.56%; range 0%-6.54%) and AI random (median 0.30%; range 0%-3.21%) showed considerable intertumor variability. Moreover, 53% of the evaluated PNET showed a more than two-fold difference between AI hot spot and AI random, showing important intratumoral variability of the abundance of apoptotic cells in a subset of the evaluated PNET. No significant associations were found between AI hot spot and AI random with clinical variables or survival outcome. CONCLUSION: The apoptotic index does not predict survival outcome and is not specifically associated with clinical variables of prognostic significance in childhood PNET. PMID- 11196267 TI - Prospective randomized trial between two doses of granulocyte colony-stimulating factor after ifosfamide, carboplatin, and etoposide in children with recurrent or refractory solid tumors: a children's cancer group report. AB - PURPOSE: The objectives of this study were: 1) to compare the time to hematologic recovery (absolute neutrophil count [ANC] > or = 1,000/mm3 and platelet count > or = 100,000/mm3) in a randomized prospective study of two doses of granulocyte colony-stimulating factor (G-CSF) (5.0 vs. 10.0 microg/kg per day) after ifosfamide, carboplatin, and etoposide (ICE) chemotherapy; and 2) to determine the response rate (complete response [CR] + partial response [PR]) of ICE in children with refractory or recurrent solid tumors. PATIENTS AND METHODS: From June 1992 until November 1994, 123 patients with recurrent or refractory pediatric solid tumors were treated with ifosfamide (1,800 mg/m2 per day x 5), carboplatin (400 mg/m2 per day x 2), and etoposide (100 mg/m2 per day x 5) and randomized to receive either 5.0 microg/kg per day or 10.0 microg/kg per day of G CSF subcutaneously until recovery of ANC to > or = 1,000/mm3. RESULTS: The incidence of grade 4 neutropenia during the first course was 88%. Median time from the start of chemotherapy to ANC > or = 1,000/mm(-3) for all patients during courses 1 and 2 was 21 and 19 days, respectively. The incidence of developing platelet count < or = 20,000/mm3 during course 1 was 82%. The median time from the start of the course of chemotherapy to platelet recovery > or =100,000/mm3 for all patients during courses 1 and 2 was 27 days. There was no significant difference in the median time of ANC recovery, platelet recovery, or incidence of grade 4 neutropenia; and in the median days of fever and the incidence of infections requiring hospitalization and intravenous antibiotics during courses 1 and 2, there was no significant difference between the two doses of G-CSF. One hundred eighteen patients were evaluated for response to ICE. The overall response rate (CR + PR) in this study was 51% (90% confidence interval, 43%-59%). The CR rate for all diagnostic categories was 27%. The Kaplan-Meier estimates of 1-year and 2-year survival probabilities for all patients were 52% and 30%, respectively. CONCLUSION: In summary, this combination of chemotherapy (ICE) was associated with a high CR rate (27%) in children with recurrent or refractory solid tumors, but also with a high incidence of grade 4 neutropenia and thrombocytopenia. Doubling the dose of G-CSF from 5.0 to 10.0 microg/kg per day after ICE chemotherapy did not result in an enhancement of neutrophil or platelet recovery or the incidence of grade 4 neutropenia developing. PMID- 11196268 TI - Osteogenic sarcoma associated with Diamond-Blackfan anemia: a report from the Diamond-Blackfan Anemia Registry. AB - PURPOSE: Diamond-Blackfan anemia (DBA) is a congenital pure red cell aplasia, usually presenting in infancy or early childhood. A review of the literature strongly supports a predisposition to hematopoietic malignancy. Recently, solid tumors have been reported, some attributable to hemosiderosis and/or androgen therapy. Two cases of osteogenic sarcoma have also been documented. An analysis from the Diamond-Blackfan Anemia Registry was performed to evaluate the cancer risk in patients with DBA. METHODS: The Diamond-Blackfan Anemia Registry of North America (DBAR) is a comprehensive database of patients with DBA enrolled, after informed consent, through outreach to pediatric hematologists and family groups. The patients and/or their families complete a detailed questionnaire, and a review of medical records and telephone interviews are performed to complete and clarify the information provided. RESULTS: Of the 354 patients registered in the DBAR, there were six patients meeting the accepted diagnostic criteria for DBA who were found to have malignancies. Three patients had osteogenic sarcoma diagnosed, one with myelodysplastic syndrome, one with colon carcinoma, and one with a soft tissue sarcoma. CONCLUSION: There appears to be an association of osteogenic sarcoma with DBA. A young age at presentation may be a feature of DBA associated osteogenic sarcoma. Because of the immaturity of the database, the actuarial risk for osteogenic sarcoma and other cancers in individuals with DBA cannot be ascertained. Speculation is made regarding the nature of the molecular defect leading to the association of DBA and osteogenic sarcoma. PMID- 11196269 TI - Chemotherapy-induced unconjugated hyperbilirubinemia caused by a mutation of the bilirubin uridine-5'-diphosphate-glucuronosyltransferase gene. AB - Chemotherapy for malignant neoplasms sometimes causes unconjugated hyperbilirubinemia in the absence of liver dysfunction. We analyzed the association of chemotherapy-induced hyperbilirubinemia with mutations of the bilirubin uridine-5'-diphosphate (UDP)-glucuronosyltransferase gene (UGT1A1) from two leukemic patients in whom chemotherapy resulted in a hyperbilirubinemic response. We isolated genomic DNA from peripheral blood samples and amplified UGT1A1 by polymerase chain reaction. The amplified DNA fragments were analyzed by direct sequencing. The genes of the two patients revealed an identical heterozygous missense mutation in exon 1 (211G-->A: G71R). This UGT1A1 mutation may be the basis of chemotherapy-induced unconjugated hyperbilirubinemia. PMID- 11196270 TI - Secondary myelodysplasia with monosomy 7 arising after treatment for acute lymphoblastic leukemia in childhood. AB - Monosomy 7 is recognized as a characteristic, clonal abnormality associated with acquired myelodysplasia (MDS) or acute myeloid leukemia (AML). It can occur as a late complication of cytotoxic therapy and is usually associated with exposure to alkylating agents or radiation therapy. We report two patients with therapy related myelodysplasia (t-MDS) associated with monosomy 7 occurring in children after completion of therapy for acute lymphoblastic leukemia (ALL). Both children were noted to have t-MDS with monosomy 7 at the time of cessation of chemotherapy. Neither child had received an alkylating agent or radiation therapy during treatment. One child had a unique dicentric marker chromosome that was shown by fluorescent in situ hybridization to be derived from chromosome 7. This report emphasizes the need to identify and minimize therapy-related side effects without compromising cure rates. PMID- 11196271 TI - Successful treatment of disseminated relapsed medulloblastoma in an infant by primary radiotherapy. AB - An infant who experienced disseminated relapse of medulloblastoma while receiving chemotherapy is described. He was subsequently treated with radiation therapy. Seven and one-half years from diagnosis, he is currently disease-free and enjoys a relatively normal life. We emphasize the importance of considering radiation as one of the treatment modalities for young children with relapsed medulloblastoma. PMID- 11196272 TI - Treatment of Langerhans cell histiocytosis with pamidronate. AB - A 14-year-old boy with longstanding multisystem Langerhans cell histiocytosis (LCH) had multifocal bone pain unresponsive to chemotherapy, corticosteroids, anti-inflammatories, and narcotic analgesics. He responded to two cycles of intravenous pamidronate, each 90 mg per day on three consecutive days. Two subsequent episodes of deterioration also responded to treatment. The pathophysiology of his bone pain and the likely mechanisms of biphosphonate action are discussed, with emphasis on the molecular and cellular basis of LCH. PMID- 11196273 TI - Clearance of TT virus after allogeneic bone marrow transplantation. AB - A 10-year-old girl with thalassemia underwent bone marrow transplantation. Before transplantation, she had persistent TT virus (TTV) DNAemia for at least 18 months. Interestingly, the viral DNAemia was cleared soon after transplant and remained undetectable at the latest follow-up at 28 months. The early clearance of TTV that had occurred before engraftment or initiation of any antiviral therapy, together with the absence of TTV DNA from the results of the liver biopsy performed before transplantation, led us to hypothesize that the hematologic compartment could have been the site for viral persistence. Thus, the conditioning regimen may have depleted the hemic cells and the hematologically compartmentalized TTV. The potential of hemic tropism of TTV and its role in hematologic diseases need to be considered. PMID- 11196274 TI - Extracutaneous Sweet syndrome involving the gastrointestinal tract in a patient with Fanconi anemia. AB - Acute febrile neutrophilic dermatosis, or Sweet syndrome, is a cutaneous eruption characterized clinically by the appearance of painful red plaques and nodules and histologically by an intense dermal neutrophilic infiltrate. Extracutaneous manifestations are rare. We report a patient in whom otherwise typical cutaneous Sweet syndrome was accompanied by an extracutaneous manifestation in the ileum. PMID- 11196275 TI - Congenital dyserythropoietic anemia type 1 with fetal onset of severe anemia. AB - We report a patient with congenital dyserythropoietic anemia type 1 with characteristic anomalies and two novel clinicopathologic presentations: intrauterine onset of severe anemia resulting in cardiac failure and relatively mild dyserythropoietic features on bone marrow aspiration in contrast to severity of anemia. After repeated transfusions and a trial of erythropoietin administration, the patient died from respiratory infection at age 7 months. Autopsy revealed characteristic dyserythropoietic features of the bone marrow by light microscopy and electron microscopy, which confirmed a diagnosis of congenital dyserythropoietic anemia type 1. PMID- 11196276 TI - An infant with homozygous hemoglobin D-Iran. AB - Hemoglobin D-Iran (Hb D-Iran, beta 22 Glu-->Gln) is a beta-chain variant that was first described in 1973. Hb D-Iran in combination with normal Hb A (Hb D-Iran trait) is a benign condition. Hb D-Iran has also been described in combination with sickle hemoglobin and beta thalassemia, but never as a homozygous mutation. The authors describe a case of homozygous Hb D-Iran in an infant of Pakistani descent. The hematologic values, hemoglobin electrophoresis, peripheral blood smear, and clinical course to date suggest that homozygous Hb D-Iran is a relatively benign condition with mild microcytic anemia, poikilocytosis, and minimal hemolysis. PMID- 11196277 TI - Treatment of hemolytic disease of the newborn caused by anti-Kell antibody with recombinant erythropoietin. AB - Recent data suggest that antibody-mediated suppression of erythroid progenitors may contribute to the anti-Kell-induced alloimmune hemolytic disease of the newborn (HDN). A 32-week-old girl who was positive for Kell was born to a mother who was negative for Kell but known to have anti-Kell antibodies. After birth, the baby had HDN and hyperbilirubinemia develop (peak bilirubin 21 mg/dL at day 9 of life). which was treated with phototherapy. Although the hyperbilirubinemia resolved, she became progressively anemic (hematocrit 22%) with an inappropriately low reticulocyte response (1.1%) and erythropoietin (EPO) level (20 mU/mL). To avoid the need for a blood transfusion, she was treated with recombinant erythropoietin (rEPO) and oral iron supplements. One week after starting EPO, the reticulocyte count increased to 9.1%. Erythropoietin therapy was continued for a total of 9 weeks, with resolution of her anemia at the end of therapy (hematocrit 35%). Thus, we were able to successfully treat the anemia with rEPO with avoidance of blood transfusion. This patient demonstrates that the antibody-mediated erythroid suppression in Kell alloimmune anemia can be overcome by rEPO. Recombinant erythropoietin should therefore be considered in the management of infants with severe or hypoproliferative anti-Kell-associated anemia. PMID- 11196278 TI - Treatment of Epstein-Barr virus-associated posttransplant lymphoproliferative disorders. PMID- 11196279 TI - Unusual complication of sickle cell crisis. PMID- 11196280 TI - Vincristine-induced fever in a child with rhabdomyosarcoma: cellular hypersensitivity to vincristine demonstrated by leukocyte migration test. PMID- 11196281 TI - The myth of informed consent. PMID- 11196282 TI - Smoking status in pregnant women assessment of self-report against carbon monoxide (CO). AB - Smoking according to self-report and to carbon monoxide (CO) were examined in 7,405 pregnant women who agreed to complete a breath test and questionnaire. The sensitivity and specificity of self-report against CO, and predictors of a high CO among reported nonsmokers, were examined. The prevalence of reported smoking was 23% (95% CI: 19.4-26.4), and 20% had a CO of 9 or more (95% CI: 17.0-23.1). The sensitivity and specificity against CO were 87% (95% CI: 83.1-91.6) and 93% (95% CI: 91.9-94.6). The positive predictive value was 76% (95% CI: 73.2-79.8), reflecting CO's inability to detect light smoking. The negative predictive value was 97% (95% CI: 95.6-97.8). The best predictors of high CO among reported nonsmokers were being divorced/separated (9.8% had high CO), quitting during pregnancy (8.5% had high CO), being third trimester, and high passive exposure. Some pregnant women may report inaccurately despite validation. Difficulties remain in determining the contributions of passive exposure and inaccurate report to inconsistencies between biochemical and self-report measures. PMID- 11196283 TI - A family study of homeland Korean alcohol use. AB - Survey data were obtained from 199 homeland Korean families consisting of 199 sets of parents, and 300 college-age sons (162) and daughters (138). Data were obtained regarding quantity and frequency of alcohol consumption by users and of judgments of what constituted "normal" and "problem" alcohol use, flushing status, symptoms experienced following alcohol use, reasons for drinking given by users, and reasons for abstaining given by abstainers. Fathers and sons differed little in use status, but daughters were abstainers far less often than their mothers. Female users drank a good deal less than males, fathers and sons differed slightly, while daughters drank considerably more than their mothers. Own use was substantially correlated with judgments of the nature of normal use and far less related judgements of problem use. There was a significant difference in fast versus slow skin flushing. with a higher proportion of females being fast flushers. Fast flushers drank less than slow flushers and also judged lower amounts of consumption as being "normal." Fast flushers experienced more physical symptoms than slow flushers; persons who drank more experienced fewer symptoms. Males more than females, slow flushers more than fast flushers, and heavy more than light users of alcohol are more likely to endorse a variety of reasons for drinking. Reasons for not drinking differ little across family membership groups. Contemporary homeland Koreans drink less than would have been expected on the basis of prior research, even though there is a substantial generational difference among females, with daughters being less frequently abstainers and drinking more, and more often than their mothers. PMID- 11196285 TI - Behavioral characteristics related to substance abuse and risk-taking, sensation seeking, anxiety sensitivity, and self-reinforcement. AB - Given the multitude of negative outcomes associated with substance abuse and other risk-taking behaviors, the current study sought to investigate sensation seeking, anxiety sensitivity, and self-reinforcement as they relate to participation in high-risk behaviors with 155 undergraduate students. The measures were the Reckless Behavior Questionnaire, Sensation Seeking Scale, Anxiety Sensitivity Index, Heiby Self-Reinforcement Questionnaire, and a sample of items from the treatment factor of the Substance Abuse Attitude Survey. Significant multivariate effects were attributable to sensation seeking and anxiety sensitivity. Sensation seeking and anxiety sensitivity were significant predictors of substance abuse. The model significantly predicted risky sexual behavior with a positive relationship between sensation seeking and risky sexual behavior. High anxiety-sensitivity scores were associated with a greater reported incidence of high-risk sexual practices. Participants highest in sensation seeking were most likely to engage in reckless driving, with male incidence being greater than for females. An unexpected finding was that anxiety sensitivity negatively correlated with substance abuse. PMID- 11196284 TI - Correlates of mental health service utilization and unmet need among a sample of male adolescents. AB - The authors sought to identify the correlates of mental health services utilization and unmet need for these services among a sample of adolescent males. We hypothesized that our findings would replicate and extend those of the recent Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) study, which found that parental factors play a major role in their children's unmet mental health care needs. Our study involved an evaluation of mental health service utilization and unmet need during the prior 2 years, as reported by the subjects at a follow-up assessment at age 16. Four factors were found to predict increased mental health services utilization, including attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) among the adolescent males, the father's alcohol use disorder, and the mother's amphetamine use disorder. One factor was found to predict decreased utilization, the father's cannabis use disorder. Four factors significantly predicted unmet treatment need, including conduct disorder, the mother's amphetamine use disorder, a higher number of siblings, and a parental history of having had a childhood anxiety disorder. The results of this study suggest that parental psychopathology, parental substance abuse, the presence of conduct disorder, and an increased number of siblings act as barriers to adequate mental health treatment among adolescents. These findings confirm the crucial role that parental factors play in the treatment utilization and the unmet treatment need of their children, and also suggest that an increased number of siblings can also be associated with unmet treatment need. PMID- 11196286 TI - Processes of changing gambling behavior. AB - Recovered problem gamblers (N = 37) described the processes used in overcoming their gambling problem using a modified version of the Processes of Change Questionnaire (J. O. Prochaska, W. F. Velicer, C. C. DiClemente, & J. S. Fava, 1988). The most frequently used processes were cognitive-experiential in nature and included self-reevaluation, environmental reevaluation, dramatic relief, and self-liberation. The least-used processes were reinforcement management and social liberation. Individuals who had sought gambling treatment reported greater use of most processes, in particular cognitive-experiential ones, compared with self-changers. The processes reported by participants were similar to those elicited through open-ended questions, but the results for problem gamblers differ from results of studies of other types of behavior change. PMID- 11196287 TI - Effect of current tobacco use and history of an alcohol problem on health status in hospitalized patients. AB - This prospective study assessed the relationship between current tobacco use and history of an alcohol problem to health status in hospitalized patients. Factors associated with current tobacco use and history of an alcohol problem were also evaluated. Data were collected using a self-administered survey distributed by nursing staff to adult inpatients registered on April 27, 1994 at the Mayo Clinic, Rochester, Minnesota affiliated hospitals. Respondents (N = 589, 45% female) were classified into 4 subgroups based on current tobacco use status and history of an alcohol problem: (a) current tobacco use only (n = 94, 16%); (b) history of an alcohol problem only (n = 30, 5%); (c) both (n = 27, 5%); or (d) neither (n = 438, 74%). Patients with both current tobacco use and an alcohol problem history reported markedly lower scores on health status measures of general and mental health compared to the other three subgroups. Moreover, current tobacco use and history of an alcohol problem were each associated with increased psychological distress. Current tobacco use was predictive of a history of an alcohol problem and vice versa. PMID- 11196288 TI - Concurrent prediction of drug use among high-risk youth. AB - Correlates of drug use were examined in a continuation high school sample (n = 1.315), using canonical correlation analysis. Fourteen demographic, attitudes/belief, and psychosocial pressure/ anxiety-type variables were included as concurrent predictors. Eight drug-use-related measures were also placed into the analysis as outcome variables. Two factors were revealed. White ethnicity, not being Latino, all attitude/belief measures, and family conflict and depression showed relatively high loadings on the first predictor factor, and were associated with all drug-use measures. Latino ethnicity and being relatively unacculturated (i.e., tending to speak Spanish), most of the attitude/belief measures (but not sensation seeking or spirituality), and perceived peer approval to use drugs, trait anxiety, and depression showed relatively high loadings on the second predictor factor, and were associated with the hard-drug-use measures. These results suggest that there is a subgroup of unacculturated Latino youth who are anxious, who perceive they will achieve peer approval by using drugs, and who tend to use hard drugs. Indicated drug abuse prevention strategies may need to be tailored to this subgroup when developing and implementing programming. PMID- 11196289 TI - Individual change amid stable smoking patterns in polydrug users over 3 years. AB - The pattern of stability/change in smoking status was examined annually in 254 community-dwelling polydrug users over 3 years. Respondents' smoking status was classified as nonsmoker, intermittent smoker, or "everyday" smoker. Results showed that the typical probability of retaining the same smoking status across any two consecutive assessments was: 0.77 for nonsmokers (never smokers and former smokers combined), 0.82 for everyday smokers, and 0.16 for intermittent smokers. The transition matrix proved stable across three observations; the predicted equilibrium distribution matched well with observed distributions. Fifty-five percent of intermittent smokers converted to everyday smoking within a year, but 29% converted to former-smoker status in the same period. No other transition exceeded 12%. Considerable flux in individual smoking status, particularly among intermittent smokers, was observed despite stable prevalence of smoking status in this population. Intermittent smoking status appeared to be a temporary "way station" between the two more stable everyday smoker and nonsmoker classifications. Results challenge current assumptions about "occasional" or "chipper" smokers. PMID- 11196290 TI - Smoking status and psychosocial variables in type 1 diabetes mellitus. AB - While depression, anxiety, and negative affect are associated with smoking and smoking cessation outcomes in healthy individuals, these associations have not been established in smokers with chronic diseases such as diabetes mellitus, a condition which greatly increases cardiovascular disease risk. Other psychosocial variables such as stress and locus of control may also be associated with smoking but are seldom reported. We examined stress, affect, and locus of control by smoking status in patients with type 1 diabetes mellitus. Results indicated that current smokers reported significantly higher levels of perceived stress, a more negative affect, and higher powerful others locus of control compared with nonsmokers. These findings indicate that those patients who have diabetes and who smoke are at greater risk for depressive symptoms. This knowledge may aid clinicians in their attempts to help these patients quit smoking. PMID- 11196291 TI - The context-specific positive alcohol outcome expectancies of university women. AB - Alcohol outcome expectancies are subjective beliefs about the psychological and physical effects of alcohol consumption. The primary purpose of the present study was to determine whether the types and strengths of university women's positive alcohol outcome expectancies differ across three typical student drinking contexts. Seventy-eight female undergraduates completed three versions of the Expectancy Context Questionnaire (ECQ) depicting Social, Sexual, and Tension drinking contexts, respectively, and then prospectively self-monitored their own drinking behavior. Respondent's total positive expectancies were strongest, overall, in the Sexual context and weakest in the Tension context. Consistent with hypothesis, the strengths of certain specific alcohol expectancies varied significantly across contexts: Arousal expectancies were strongest in the Sexual context and weakest in the Social context; Social/Sexual Enhancement expectancies were strongest in the Sexual context and weakest in the Tension context; and Global Positive Affect expectancies were strongest in the Social context and weakest in the Tension context. Drinking levels over the week of self-monitoring were significantly predicted by Global Positive Affect and Relaxation expectancies in the Social Context, and by Social/ Sexual Enhancement, Arousal, and Relaxation expectancies in the Sexual Context. The theoretical and clinical importance of identifying drinking context when examining alcohol expectancies is discussed. PMID- 11196292 TI - Drug-use behavior and correlates in people with schizophrenia. AB - This study examined how illicit drugs were accessed, reasons for drug use, prevalence of emotional, physical, and sexual abuse, psychiatric symptomatology, level of functioning, and the relationship of these factors to substance use in 25 schizophrenia outpatients. To identify unique substance-use behaviors or correlates, this information was compared to 25 substance-abusing outpatients with major affective disorders, and 30 people with schizophrenia alone. Patients largely financed their drug habits with money given by immediate family members, and reported using drugs primarily for social reasons. While all three groups reported high levels of physical, sexual, and emotional abuse, a relationship between emotional abuse and substance use was observed only for people with schizophrenia. There were no differences between the two schizophrenia groups in psychiatric symptoms or level of functioning. The treatment implications of these findings are discussed. PMID- 11196293 TI - Co-occurrence of alcohol and cigarette use among adolescents. AB - Concurrent use of alcohol and cigarettes among adolescents is a serious public health issue. Trends in concurrent use of alcohol and cigarettes were determined using data from three comparable large statewide samples of 7-12th-grade students in New York State, from surveys conducted in 1983, 1990, and 1994. The prevalence of use of alcohol and cigarettes decreased from 1983 (23%) to 1990 (19%), and increased by 1994 (22%). Logistic regression analysis showed that these trends are highly significant, and that the probability of use of alcohol and cigarettes is higher for females than males, increases with age, and is lower for most ethnic minorities than for Whites. In the 1990s, Blacks, Hispanics, and Asians increased in their probability of concurrent use more than did Whites. Users of both alcohol and cigarettes are at increased risk of personal and social problems, as well as increased risk of delinquency. Drinking and smoking show synergistic effects on illicit drug use and drug problems. PMID- 11196294 TI - Sources of motivation for abstinence: a replication analysis of the reasons for quitting questionnaire. AB - The Reasons for Quitting Questionnaire (RFQ) as modified by McBride and colleagues (C. M. McBride et al., 1994) for use with substance users other than tobacco smokers, was administered to individuals approved for public-sector addiction treatment. Four motivation dimensions, similar to those found by McBride et al., were identified: self-concept issues, health concerns, legal issues, and social influence. A forced two-component solution yielded dimensions interpretable as intrinsic and extrinsic motivation. Self-concept issues provided the highest levels of motivation for abstinence in this sample, with moderate levels provided by health concerns, and the lowest levels provided by legal and social influence components. Intrinsic motivation was higher than extrinsic motivation. Logistic regression models, with adjustment for total motivation, tested the association of successful abstinence during a follow-up period with baseline extrinsic and intrinsic motivation, and with the difference between intrinsic and extrinsic levels. All three associations were significant: intrinsic motivation (positive association), extrinsic motivation (negative association), and the difference score (positive association). The results suggest the usefulness of the 20-item modified RFQ in evaluating motivation for abstinence among treatment seekers exhibiting severe negative consequences of addiction. Testing with samples varying in severity of addiction consequences is recommended. PMID- 11196295 TI - Interest in different forms of self-help in a general population sample of drinkers. AB - The study investigates: (1) the level of interest in self-help services for drinkers, and (2) the predictors of interest in these services. A representative sample of 1,557 Ontario respondents participated in a telephone survey. Current drinkers (n=1,247) were asked about their interest in getting: (a) a telephone call from a therapist to help them evaluate their drinking, (b) a self-help book, and (c) a computerized summary comparing their drinking to that of other Canadians. Bivariate comparisons of demographic and drinking-related variables were made between those interested and not interested in each of the offered services. Logistic regression analysis was used to find the best predictors of interest. The results revealed that 16% were interested in a telephone call, 26% in a self-help book, and 39% in computerized normative feedback. Negative consequences of drinking and indicators of lower societal resources increased interest in self-help services. Computerized feedback and self-help books serve as cheap and nonintrusive ways to provide incentive for change to early-stage problem drinkers due to the interest they raise in the intended target population. PMID- 11196296 TI - Brave new monkey. PMID- 11196297 TI - The ultimate diet plan. Don't eat so much. PMID- 11196298 TI - Seeing a virtual shrink. PMID- 11196299 TI - Hybridization screening of very short PCR products for paleoepidemiological studies of Chagas' disease. AB - Single strands of very short PCR products can be covalently immobilized to a slide and then easily detected by probe hybridization. In this work, the PCR product was a 70-nucleotide segment of ancient DNA, representing a portion of repeat mini-circle DNA from the kinetoplast of Trypanosoma cruzi, the infectious agent of Chagas' disease (American Trypanosomiasis). The target segment was initially established to be present in soft tissue samples taken from four "naturally" mummified Andean bodies using PCR followed by cloning and sequencing. Hybridization screening of the covalently immobilized PCR products positively identified products from 25 of 27 specimens of different tissues from these four mummies. The method appears to be ideal for the purpose of screening a large number of specimens when the target PCR product is very short. PMID- 11196300 TI - Spreadsheet-based program for the analysis of DNA methylation. AB - Methylation of DNA in CpG dense regions of gene promoters (CpG islands) is important for transcriptional inactivation of selective genes in normal and neoplastic cells. Here, we present a spreadsheet-based program adapted from Microsoft Excel that is useful for identifying CpG islands and for assisting in the laboratory analysis of DNA methylation of these regions. Upon execution of the program, a customized workbook analyzes an entered DNA sequence for the total number and percentage cytosine and guanine nucleotides, the total number and percentage of CpG sites, and a CpG:GpC ratio. The program also displays the distribution of CpG sites in a visual format as well as in two different graphical formats. Finally, the program assists in laboratory studies of DNA methylation that employ bisulfite modification of DNA by displaying methylation dependent effects of bisulfite treatment on DNA sequences. PMID- 11196301 TI - Microsoft Word macro for analysis of cytosine methylation by the bisulfite deamination reaction. AB - Cytosine methylation at CpG dinucleotides is an important control mechanism in development, differentiation, and neoplasia. Bisulfite genomic sequencing and its modifications have been developed to examine methylation at these CpG dinucleotides. To use these methods, one has to (i) manually convert the sequence to that produced by bisulfite conversion and PCR amplification, taking into account that cytosine residues at CpG dinucleotides may or may not be converted depending on their methylation status, (ii) identify relevant restriction sites that may be used for methylation analysis, and (iii) conduct similar steps with the other DNA strand since the two strands of DNA are no longer complementary after bisulfite conversion. To automate these steps, we have developed a macro that can be used with Microsoft Word. This macro (i) converts genomic sequence to modified sequence that would result after bisulfite treatment facilitating primer design for bisulfite genomic sequencing and methylation-sensitive PCR assay and (ii) identifies restriction sites that are preserved in bisulfite-converted and PCR-amplified product only if cytosine residues at relevant CpG dinucleotides are methylated (and thereby not converted to uracil) in the genomic DNA. PMID- 11196302 TI - Conversion of capillary electrophoresis microchip genotyping data for analysis with Genetic Profiler software. AB - The collection and conversion of 4-color fluorescent genotyping data from capillary array electrophoresis microchip devices and its conversion to a format easily and rapidly analyzed by Genetic Profiler genotyping software is presented. Microchip fluorescence intensity data are acquired and stored as 4-color tab delimited text. These files are converted to electrophoretic signal data (ESD) files using a utility program (TEXT-to-ESD) written in C. TEXT-to-ESD generates an ESD file by converting text data to binary data and then appending a 632-byte ESD-file trailer. Up to 96 ESD files are then assembled into a run folder and imported into Genetic Profiler, where data are reduced to 4-color electropherograms and analyzed. In this manner, DNA fragment sizing data acquired with our high-speed electrophoretic microchip devices can be rapidly analyzed using robust commercial software. Additionally, the conversion program allows sizing of data with Genetic Profiler that have been preprocessed using other third-party software, such as BaseFinder. PMID- 11196303 TI - MouseBank: a database application for managing transgenic mouse breeding programs. PMID- 11196304 TI - Labeling DNA with stable isotopes: economical and practical considerations. AB - Labeling DNA with stable isotopes to measure cell proliferation can be a technique as effective as 3H-thymidine labeling without the limitations imposed by using radioisotopes. Here, we investigated the relative efficiency of four nonradioactive precursors to DNA: [1-13C]-glycine, [1,2-13C2]-glycine, [U-13C] glucose, and [U-13C, 15N]-thymidine. The efficiency of incorporation for each of these labeled precursors in HEP G2 cells in culture has been studied. When considering the actual costs of in vivo experiments in which large doses of labeled material are needed, economical constraints may play an important role in defining a practical method. Therefore, the economics of this process were also considered. Using the enrichment per dollar for whichever nucleoside had the highest incorporation in a given experiment, glycine is about five times more economical as a label than thymidine and eight times more economical than glucose in these cells. PMID- 11196305 TI - Detection of small sequence differences using competitive PCR: molecular monitoring of genetically improved, mercury-reducing bacteria. AB - A quantitative PCR approach is presented to detect small genomic sequence differences for molecular quantification of recombinant DNA. The only unique genetic feature of the mercury-reducing, genetically improved Pseudomonas putida KT2442::mer73 available to distinguish it from its native mercury-resistant relatives is the DNA sequence crossing the border of the insertion site of the introduced DNA fragment. The quantification assay is a combination of specific PCR amplification and temperature gradient gel electrophoresis (TGGE). Gene quantification is provided by a competitively co-amplified DNA standard constructed by point mutation PCR. After computing the denaturation behavior of the target DNA stretch, a single base difference was introduced to achieve maximum migration difference in TGGE between the original target DNA and the modified standard without altering the PCR amplification efficiency. This competitive PCR strategy is a highly specific and sensitive way to detect small sequence differences and to monitor recombinant DNA in effluxes of biotechnological plants. PMID- 11196306 TI - Quantitative detection of Chlamydia spp. by fluorescent PCR in the LightCycler. AB - Quantitative detection of intracellular bacteria of the genus Chlamydia by the standard cell culture method is cumbersome and operator dependent. As an alternative, we adapted hot-start PCR to the glass capillary quantitative PCR format of the LightCycler. The optimized PCR was consistently more efficient than commercially available pre-assembled PCRs. Detection by quantitative PCR of as few as single copies of DNA of Chlamydia spp. was accomplished by SYBR Green fluorescence of the dsDNA product and by fluorescence resonance energy transfer (FRET) hybridization probes. The PCRs were 15-fold more sensitive than the cell culture quantitative assay of C. psittaci B577 infectious stock. The number of chlamydial genomes detected by C. psittaci B577 FRET PCR correlated well with cell culture determination of inclusion forming units (IFUs) (r = 0.96, P < 0.0008). When infected tissue samples were analyzed by cell culture and PCR, the correlation coefficient between IFUs and chlamydial genomes was higher with C. psittaci B577 FRET PCR (r = 0.90, P < 0.0004) than with Chlamydia omp1 SYBR Green PCR (r = 0.85, P < 0.002). PMID- 11196307 TI - Use of SMART-generated cDNA for gene expression studies in multiple human tumors. AB - We demonstrate here that SMART PCR-amplified cDNAs arrayed on a nylon membrane are suitable for high-throughput tissue expression profiling when starting biological materials are limited. We show that SMART cDNA accurately reflects gene expression patterns found in total RNA by comparing the expression level of several target genes in SMART PCR-amplified cDNAs and their corresponding total RNAs. We also arrayed cDNAs from 68 matched tumor and normal samples on a nylon membrane to determine whether SMART PCR-amplified cDNA could be used for detecting differentially expressed genes in these tissues. These arrays containing normalized tumor and normal cDNAs were hybridized with probes for glutathione peroxidase and gelsolin. The hybridization results revealed cancer related and patient-specific gene expression differences between tumor and normal tissues for these genes. These studies show that SMART PCR-amplified cDNAs maintain the complexity of the original mRNA population and are thus suitable for high-throughput studies to compare the relative abundance of target genes and to detect differentially expressed genes in a wide variety of tissues simultaneously. PMID- 11196308 TI - Genes to drugs. PMID- 11196309 TI - Current concepts in cancer vaccine strategies. AB - Cancer vaccines are entering a new phase of popularity, in part because of the recognition of when a therapeutic vaccine is most effective and the identification of appropriate target antigens. New technologies, most notably gene transfection into dendritic cell and DNA vaccination approaches, have spurred further clinical evaluations. While many researchers consider humoral responses as not being viable for large tumors, these responses may play a role in regulating micrometastases (i.e., adjuvant setting). The recent approval of antibodies as therapeutics for cancer treatment has lent to the viability of this therapy concept. The success of carbohydrate-conjugate vaccines in bacterial systems has also renewed interest in developing such vaccines for cancer immunotherapy. Carbohydrates can be further converted into peptide/protein mimetics with several of these mimetics in clinical trials. These mimetic forms can be manipulated into DNA vaccine types that may be combined into DNA cassettes that contain CTL-associated epitopes to further define a novel strategy for future vaccine development. PMID- 11196311 TI - Improved methylation protection-based DNA footprinting to reveal structural distortion of DNA upon transcription factor binding. PMID- 11196310 TI - Generation and characterization of recombinant vascular targeting agents from hybridoma cell lines. AB - Vascular targeting agents (VTAs) can be produced by linking antibodies or antibody fragments directed against endothelial cell markers to effector moieties. So far, it has been necessary to produce the components of VTAs (antibody, antibody fragment, linker, and effector) separately and, subsequently, to conjugate them by biochemical reactions. We devised a cloning and expression system to allow rapid generation of recombinant VTAs from hybridoma cell lines. The VTAs consist of a single chain Fv antibody fragment as a targeting moiety and either truncated Pseudomonas exotoxin (resulting in immunotoxins) or truncated human tissue factor (resulting in coaguligands) as effectors. The system was applied to generate recombinant immunotoxins and coaguligands directed against endoglin, vascular endothelial growth factor (VEGF):VEGF receptor (VEGFR) complex and vascular cell adhesion molecule 1 (VCAM-1). The fusion proteins exhibited similar functional activity to analogous biochemical constructs. This is the first report to describe the generation and characterization of recombinant coaguligands. PMID- 11196312 TI - Maximization of signal derived from cDNA microarrays. AB - Microarray technology is a powerful tool for generating expression data on a large number of genes simultaneously. However, as for any assay, it must be reproducible to give confidence in the results. Using a classical statistical method--the factorial design of experiments--we have assessed the effects of different experimental factors in our system. Significant effects on signal were seen when the standard components were substituted with a different enzyme, fluorescent label, or RNA purification method. This has led to the implementation of an improved procedure that maximizes signal without affecting the variability of the system, thus increasing the signal-to-noise ratio. In addition, we were able to quantify the variability between microarrays and replicates within microarrays. PMID- 11196313 TI - Genotools SNP manager: a new software for automated high-throughput MALDI-TOF mass spectrometry SNP genotyping. AB - Analysis of single nucleotide polymorphisms (SNPs) is a rapidly growing field of research that provides insights into the most common type of differences between individual genomes. The resulting information has a strong impact in the fields of pharmacogenomics, drug development, forensic medicine, and diagnostics of specific disease markers. The technique of matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) has been shown to be a highly suitable tool for the analysis of DNA. It supplies a very versatile method for addressing a high-throughput SNP genotyping approach. Here, we present the Bruker genotools SNP MANAGER, a new software tool suitable for highly automated MALDI-TOF MS SNP genotyping. The genotools SNP MANAGER administers the sample preparation data, calculates masses of allele-specific primer extension products, performs genotyping analysis, and displays the results. In the current study, we have used the genotools SNP MANAGER to perform an automated duplex SNP analysis of two biallelic markers from the promoter of the gene encoding the inflammatory mediator interleukin-6. PMID- 11196314 TI - Background activity of reverse transcriptases. PMID- 11196315 TI - Development and use of a plasmid encoding green fluorescent protein in multiple antibiotic-resistant Salmonella. PMID- 11196316 TI - Large-scale colony screening and insert orientation determination using PCR. PMID- 11196317 TI - Cost-efficient quantification of enzyme-linked immunospot. PMID- 11196318 TI - Microplate assay for the measurement of hydroxyproline in acid-hydrolyzed tissue samples. PMID- 11196319 TI - Use of DAPI staining for quantitation of cell chemotaxis. PMID- 11196320 TI - Molecular modeling on the Web. PMID- 11196321 TI - System for cleavable Fc fusion proteins using tobacco etch virus (TEV) protease. AB - We describe a novel Fc fusion protein system that can be cleaved by tobacco etch virus (TEV) protease. This system is desirable because it takes advantage of the high specificity of TEV protease and its activity at 4 degrees C. We produced two TEV-Fc fusion proteins that contain the first three Ig domains and all six Ig domains of the cell adhesion molecule L1. Both proteins were efficiently cleaved by TEV protease at 4 degrees C. Functional analysis of the cleavage products in neurite outgrowth assays showed they had similar activities to their parental Fc fusion proteins. Therefore, TEV-Fc fusion proteins may increase the utility and flexibility of the Fc fusion protein system. PMID- 11196322 TI - Promoter methylation analysis on microdissected paraffin-embedded tissues using bisulfite treatment and PCR-SSCP. AB - Methylation-sensitive single-strand conformation analysis (MS-SSCA) is a new method of screening for DNA methylation changes. The combination of bisulfite modification and PCR results in the conversion of unmethylated cytosines to thymines, whereas methylated cytosines remain unchanged. This sequence conversion can lead to methylation-dependent alterations of single-strand conformation, which can be detected by SSCA. An analysis of mixtures of methylated and unmethylated DNA at known ratios revealed that the relative intensities of the corresponding bands following MS-SSCA were maintained. MS-SSCA was applied for methylation analysis of human p16 promoter region using genomic DNA obtained from either frozen, fixed, or microdissected fixed tissue sections. MS-SSCA is a rapid, specific, and semiquantitative approach that allows the detection of methylation of the p16 gene promoter. In reconstruction experiments, the method permits the detection of 10% or less of cells harboring a methylated p16 promoter. We have been successful in analyzing by MS-SSCA almost all (96%) tumor samples microdissected from archival paraffin-embedded fixed tissue sections and obtaining reproducible results. In addition, when microdissection was performed, the clonality of this genetic alteration could be identified. PMID- 11196323 TI - Preparation of a low molecular weight polyethylenimine for efficient cell transfection. AB - Polyethylenimines (PEIs) of a molecular weight between 25 and about 800 kDa have successfully been used for in vitro and in vivo gene delivery approaches. Recent publications indicated that PEI molecules of lower molecular weight and a small molecular weight range are also efficient transfection reagents with a much lower cytotoxicity compared to high molecular weight PEIs. Here, we describe the application of a molecular sieve chromatography to fractionate a commercially available 25-kDa PEI. We generated three pools of PEIs with molecular weight ranges of 70-360 (I), 10-70 (II), and 0.5-10 kDa (III), respectively. We show that, in comparison with the 25-kDa PEI, pool III increased the expression of luciferase up to 100-fold and the number of transfected cells 2-3 fold. In addition, the kinetics of reporter gene expression was also much faster in pool III, compared with the 25-kDa PEI or with pools I or II. Finally, pool III showed the lowest cytotoxicity in comparison with the other PEI preparations. Thus, we provide a one-step processing of a 25-kDa PEI, resulting in a more effective and also less cytotoxic transfection reagent. PMID- 11196324 TI - Acetylcholinesterase assay for rapid expression screening in liquid and solid media. AB - The synaptic enzyme acetylcholinesterase (AChE), which is the target of many insecticides and potential warfare agents, is implied in Alzheimer's disease and is a good potential candidate to be used in biosensors. This promotes a strong demand for production of recombinant AChE to be used in various studies. A promising expression system is the yeast Pichia pastoris, but the expression efficiency needs to be improved. Optimization studies require a rapid and efficient screening test to detect positive yeast colonies after transformation. Using indoxylacetate as a substrate, we designed a chromogenic test that is not interfered with by the culture media background color and, thus, is suitable for microplate screening. Moreover, it was possible to adapt the test for direct on plate detection of AChE-expressing colonies. PMID- 11196325 TI - Preparation of DNA suitable for PCR amplification from fresh or fixed single dinoflagellate cells. AB - A method is described to prepare total DNA from single cells of dinoflagellates, which can be used for PCR amplification. As model organisms, we used a stock strain of Alexandrium catenella and cells of Dinophysis acuminata harvested from the Atlantic Ocean. Fresh grown cells or cells maintained in different preservatives were tested as sources for DNA preparation. The method used to prepare DNA combines physicochemical and enzymatic procedures on cells embedded in agarose plugs or beads. The agarose pieces containing the DNA were used to perform PCR amplification of a fragment of DNA containing a 5.8S rRNA gene and the flanking internal transcribed spacers (ITS1 and ITS2). PMID- 11196327 TI - Rehabilitation after amputation. AB - The principles of amputee rehabilitation, from preamputation to reintegration into the work force and community, are reviewed. The authors discuss exercise techniques, training programs, and environmental modifications that have been found to be helpful in the rehabilitation of the amputee. The exercise programs presented here are divided into four main components: flexibility, muscle strength, cardiovascular training, and balance and gait. The programs include interventions by the physical, occupational, and recreational therapist under the supervision and guidance of a physician. PMID- 11196326 TI - cDNA library screening using the SOS recruitment system. AB - The SOS recruitment system (SRS), a recently developed method for detecting protein-protein interactions, provides an attractive alternative to identify biologically important protein interactions. In SRS, the protein-protein interactions take place in the cytoplasm instead of the nucleus, as is the case in the conventional two-hybrid system. Although the SRS has overcome some of the disadvantages of the conventional two-hybrid system, it still has several problems and limitations. Here, we describe a new protocol for SRS library screening. A new combination of growth media to avoid the tedious step of replica plating greatly increases the number of independent colonies in a single library screening. Furthermore, we designed a pair of ras-specific primers and a one-step simple PCR to rule out the most abundant false positive, the mammalian ras cDNA, in SRS library screening. PMID- 11196328 TI - Primary-care interventions for the population at risk for amputation. AB - The care of patients at risk for amputation includes the identification of at risk patients, appropriate follow-up and treatment, and the anticipation of possible complications. Education and long-term follow-up are vital for management of the patient at risk for amputation. PMID- 11196329 TI - Differentiation and treatment of phantom sensation, phantom pain, and residual limb pain. AB - This article defines the three major forms of postamputation sensation: 1) phantom sensation, 2) phantom pain, and 3) residual-limb pain. Proposed etiologies for phantom pain are discussed. The literature on current diagnoses and treatments for each of the three postamputation sensations is reviewed. PMID- 11196330 TI - Use of prostheses and footwear in 110 inner-city partial-foot amputees. AB - The number of partial-foot amputations performed is increasing, and many recommendations have been made regarding the use of prostheses and footwear designed to prevent higher-level amputations in this population. The present study investigated the use of prostheses and shoe inserts and the types of footwear worn by partial-foot amputees in the inner city to determine whether previous recommendations are being followed as well as whether new prosthetic styles are being used. The study surveyed 110 patients (73 men and 37 women) with a mean age of 58.6 years (range, 21 to 86 years) with partial-foot amputations of all levels. The results showed that about one-half of all patients wore a shoe insert orthosis. Although 54% wore some form of special footwear to accommodate and protect the residual foot, no patient in this study wore a shoe with a rocker bottom sole. Only one patient with a transmetatarsal amputation used a brace and only one patient in the entire study wore a modern cosmetic foot prosthesis. PMID- 11196331 TI - Subtotal pedal amputations. Biomechanical and intraoperative considerations. AB - Proper treatment for the compromised diabetic foot often requires surgical correction and subtotal pedal amputation. This article discusses various levels of amputation of the human foot, including digital, ray, transmetatarsal, midfoot, and Syme amputations. Surgical techniques and biomechanical considerations are presented in order to assist the surgeon in planning for the most functional outcome of the patient. A review of the literature and the experiences of the authors are presented. PMID- 11196332 TI - Why I chose to be 'Dr. Beyond'. PMID- 11196333 TI - For coughs and colds, older patients need alternatives to PPA products. PMID- 11196334 TI - Once-a-week alendronate for postmenopausal osteoporosis is as effective as once daily dosing. PMID- 11196335 TI - NIH modifies trial as ACE inhibitors slow renal disease in African Americans. PMID- 11196336 TI - Prostate cancer. When to offer screening in the primary care setting. AB - Prostate cancer is the second-leading cause of cancer death in American men over age 50. Even so, consensus is lacking on whom to screen, when to screen, and what to do if cancer is discovered. The two most commonly used screening methods are digital rectal examination and serum prostate-specific antigen (PSA). PSA misses 18 to 25% of prostate cancers and provides false-positive results some 60% of the time. PSA test refinements are improving its sensitivity and specificity and therefore the early, accurate detection of prostate cancer. Whether routine screening of all men is cost-effective remains controversial--especially for men age 75 and older--but the value of screening to the individual patient is the concern of the primary care physician. PMID- 11196337 TI - Successful aging. How increased life expectancy and medical advances are changing geriatric care. AB - If the unprecedented increase in life expectancy has a downside, it is the exposure of risk to chronic age-related disorders. As clinicians work to foster healthy aging, we must also seek ways to prevent the disabling disorders that keep many older persons from enjoying their longevity. The high prevalence of chronic illness and functional limitation among older persons underscores the need for strategically directed health and social services. Successful patient management must extend beyond diagnosis and disease treatment and include promotion of function and prevention of decline. Achieving this goal requires a seamless continuum of management and interdisciplinary caregiving. There also must be a focus on improving the understanding of the science of aging. New treatment approaches for managing aging may one day include cognitive enhancers, designer hormones, telomerase, antioxidants, and gene therapy. PMID- 11196338 TI - Influenza in the older adult. Indications for the use of vaccine and antiviral therapy. AB - Each year, the influenza virus is responsible for 20,000 to 40,000 deaths and up to 300,000 hospitalizations in the United States. Although children and younger adults experience more cases of influenza, older individuals who are infected with the virus experience greater morbidity and mortality. The most effective means of influenza prevention for older adults is the influenza vaccine. Antivirals are used as adjuvant therapy, but they are not intended as primary prevention except for at-risk patients who are allergic to the vaccine. The neuroaminidase inhibitors may cause fewer side effects than the older antivirals and therefore may be a useful alternative in the treatment of influenza symptoms in older adults. PMID- 11196339 TI - Serotonin syndrome. A common but often unrecognized psychiatric condition. AB - This case illustrates that compliance with the basic principles of geriatric pharmacology (start low, go slow, and avoid polypharmacy) might have prevented a clinical syndrome that could have caused serious complications. Fortunately, serotonin syndrome was recognized early, the offending agents were discontinued, and supportive treatment was provided. The patient was ultimately treated with mirtazapine, an antidepressant not associated with serotonergic effects. PMID- 11196340 TI - Measurement of the bioavailability of aescin-containing extracts. AB - OBJECTIVE: In horse chestnut seed extracts (HCSE), the triterpene saponin mixture aescin is considered the active principle. The bioavailability and pharmacokinetics of different HCSE preparations have been studied under single and repeated applications using a radioimmunological method (RIA) developed to identify beta-aescin, one of the pharmacologically active fractions of the saponin mixture. In this paper, the available pharmacokinetic data are reviewed and the observed heterogenicity between comparable studies is discussed. DATA SOURCES: Pharmacokinetic data from 5 single- and 4 multiple-dose bioequivalence studies with HCSE-containing products, were measured by the same analytical laboratory using the same RIA. EVALUATION: In studies where procedures were identical the pharmacokinetic data of beta-aescin show high variations. Even under steady-state conditions a considerable variability for the same HCSE product is obtained. CONCLUSION: Formal reasons like study design and medications can be ruled out as a source of pharmacokinetic variation. In extracts of herbal drugs like HCS, the relative concentration of the individual saponin fractions can considerably differ from batch to batch. For immunological methods, identification of such antigens with intermolecular variability, e.g., the structural aescin analogs, is of unknown validity. Therefore the shape of the concentration-time curve would only show an approximation of the time course but not for the absolute concentrations. A specific validation procedure for the RIA must be developed, otherwise a LC-MS/MS-method of sufficient sensitivity should be elaborated. PMID- 11196341 TI - Weighting function used for adjustment of multiple-bolus drug dosing. AB - This paper presents a new method for the adjustment of the multiple-bolus dosing of a drug. The method is based on the weighting function of the system describing the behavior (absorption, distribution and elimination) of the drug in the patient, identified employing a test dose administration of the drug to a patient. This method can be employed for the adjustment of the multiple-bolus dosing of the drugs whose behavior in the patient can be sufficiently described by linear time invariant models. The method allows to estimate loading and maintenance bolus doses of the drug, necessary to reach and maintain prescribed trough levels of the drug in a patient at desired time-points, both (the levels and time-points) specified by treatment requirements. The method is particularly suitable for the adjustment of multiple-bolus dosing of drugs with narrow therapeutical windows or of very expensive products such as the clotting factors. The method is exemplified by the adjustment of the multiple-bolus dosing of factor VIII in postoperative treatment of hemophilia A. PMID- 11196342 TI - Prooxidant role of histidine in hypoxic stressed mice and Fe(3+)-induced lipid peroxidation. AB - An attempt was made to study the effect of histidine on reactive oxygen species in a rodent model of hypoxic stress and in Fe(3+)-ascorbic acid-induced lipid peroxidation in mouse brain homogenates. The latency for onset of hypoxic stress induced convulsions was decreased in histidine-treated animals with a concomitant rise in brain lipid peroxidation levels. In vitro, histidine potentiated Fe(3+) ascorbic acid-induced lipid peroxidation in mouse brain homogenates while other antioxidants like B-HT and U-74500A inhibited the same. Moreover, Fe(3+) histidine-induced lipid peroxidation could not be inhibited by preincubation of the system with high concentrations of ascorbic acid. Thus, it is concluded that histidine acts as a strong prooxidant potentiating the genesis of reactive oxygen species during hypoxic stress as well as during Fe(3+)-ascorbic acid-induced lipid peroxidation. PMID- 11196343 TI - Xylazine, an alpha 2-adrenergic agonist, modulates proliferation of rat thymocytes in vivo and in vitro. AB - The effect of xylazine, an alpha 2-adrenergic agonist, on proliferation of rat thymocytes in vivo and in vitro was examined. It was found that the agonist administered to rats in vivo at doses of 2.5 mg/kg and 5 mg/kg stimulated thymocyte proliferation to suboptimal (0.625 microgram/ml) concentrations of concanavalin A (Con A). A similar effect was confirmed in vitro when lower concentrations of xylazine (5 microM) were added to cultures of thymic cells from intact animals in the presence of both suboptimal and optimal (2.5 micrograms/ml) Con A concentrations. Higher doses in vivo (25 mg/kg) and in vitro (50 microM, 100 microM and 250 microM) significantly inhibited proliferation of thymocytes to Con A. The phenomenon was followed by a decrease in interleukin-2 (IL-2) production (in vivo and in vitro) and down-regulation of IL-2 receptor alpha (IL 2R alpha) expression (in vitro). The exogenous IL-2 completely restored the inhibitory effect of xylazine in vivo on thymocyte proliferation. However, a minimal influence of the cytokine on the xylazine-inhibited thymocyte proliferation in vitro was observed. Stimulatory effect of xylazine on proliferation of thymocytes was probably mediated through alpha 2-adrenoreceptors since it was blocked by yohimbine, an alpha 2-adrenoreceptor antagonist. It seems that the pathways involved in inhibition of thymocyte proliferation by xylazine are more complex because the xylazine-suppressed thymocyte proliferation was potentiated by yohimbine. PMID- 11196344 TI - Cardioprotective effects of citrulline in ischemia/reperfusion injury via a non nitric oxide-mediated mechanism. AB - The effects of L-citrulline, the byproduct of nitric oxide (NO) synthesis, and its stereoisomer D-citrulline were studied in a polymorphonuclear leukocyte (PMN) dependent isolated perfused rat heart model consisting of 20 min of global ischemia and 45 min of reperfusion. Ischemic hearts reperfused with either D- or L-citrulline (20 nM) exhibited a marked preservation of left ventricular developed pressure and of maximal rate of development of left ventricular developed pressure, compared to hearts perfused without either D- or L-citrulline (both p < 0.001). In addition, both D- and L-citrulline significantly attenuated PMN accumulation in the post-reperfused myocardium from 288 +/- 33 PMNs/mm2 in untreated hearts to 89 +/- 10 and 76 +/- 6 PMNs/mm2, respectively (both p < 0.001). In isolated rat aortic rings, neither D- or L-citrulline induced any vasodilation or release of nitric oxide from the vascular endothelium. However, expression of P-selectin on the coronary vascular endothelium was markedly attenuated in hearts perfused with either D- or L-citrulline compared to ischemic reperfused hearts without citrulline (both p < 0.001). These results provide evidence that D- or L-citrulline significantly attenuates PMN-induced cardiac contractile dysfunction in the isolated perfused rat heart subjected to ischemia/reperfusion via a non-NO-mediated mechanism. PMID- 11196345 TI - Renal functional responses to centrally administered ouabain in anesthetized rabbits. AB - The effects of intracerebroventricularly administered ouabain on renal function were studied in rabbits. Ouabain, when given intracerebroventricularly in doses ranging from 0.1 to 10 micrograms/kg, dose-dependently produced antidiuretic, antinatriuretic and antikaliuretic effects, along with decreases in renal perfusion and glomerular filtration rate. Systemic blood pressure also increased significantly in a dose-related fashion. No increase in free water reabsorption was noted. Intravenously administered ouabain (10 micrograms/kg) caused less pronounced antidiuresis and antinatriuresis, with the renal hemodynamics tending slightly to decrease. No significant increment of systemic blood pressure with intravenous ouabain was observed. In rabbits with one kidney denervated and the contralateral left intact, ouabain 10 micrograms/kg i.c.v. produced the typical renal effects on the intact kidney, while the denervated kidney responded with prominent natriuresis and diuresis, showing the maximal response in the second 10 min period after administration. Renal nerve activity increased significantly upon administration of ouabain 10 micrograms/kg i.c.v. and reached a peak at around 10 to 20 min after drug administration, a period in which the most remarkable antidiuresis and antinatriuresis is produced by i.c.v. ouabain. These observations suggest that the antidiuresis and antinatriuresis elicited by centrally administered ouabain results mainly from the decrease of renal hemodynamics, which is caused by the increased renal nerve activity. PMID- 11196346 TI - Effect of clarithromycin on the pharmacokinetics of carbamazepine in rhesus monkeys. AB - Clarithromycin, an advanced-generation macrolide antimicrobial, is less prone to drug interactions as compared to erythromycin. Based on two case reports in which increased carbamazepine (CBZ) plasma concentrations were observed in patients receiving clarithromycin, a crossover multiple dose study was designed to find out the pharmacokinetic interaction between CBZ and clarithromycin in rhesus monkeys. CBZ (46 mg/kg/d) was administered to the monkeys alone and along with clarithromycin (20 mg/kg/d). Blood samples were collected from 0-24 h. Plasma concentrations of CBZ were measured by HPLC technique. Pharmacokinetic data revealed an increase in plasma concentrations, AUC(0-24) and t1/2e of CBZ when coadministered with clarithromycin, but the increase was not statistically significant. These findings suggest careful administration and plasma monitoring of CBZ concentrations when coadministered with clarithromycin. PMID- 11196348 TI - Depleted credibility. Did U.S. weapons make Italian soldiers sick? PMID- 11196347 TI - Double-blind, randomized, placebo-controlled pilot study with anapsos in senile dementia: effects on cognition, brain bioelectrical activity and cerebral hemodynamics. AB - The aim of this study was to evaluate the effects of two doses of anapsos in comparison with placebo on cognitive performance, brain bioelectrical activity pattern and cerebral hemodynamic parameters in patients with mild to moderate senile dementia of vascular type and Alzheimer type. Forty-five patients (age 73.8 +/- 7.6 years; range 56-89 years) with mild to moderate senile dementia (Global Deterioration Scale: stages 3-5) of the vascular (VD; n = 22) or the Alzheimer type (AD; n = 23) were included in a double-blind randomized placebo controlled clinical trial. After a 2-week period of drug washout, patients were treated with placebo (n = 15; age 72.7 +/- 7.5 years), 360 mg/day of anapsos (n = 15; age 75.5 +/- 7.2 years), or 720 mg/day of anapsos (n = 15; age 73 +/- 7.7 years) for 4 weeks (28 days). At baseline and after the 4-week period of double blind treatment, cognitive performance, brain bioelectrical activity power and blood flow hemodynamics in the middle cerebral arteries were evaluated with ADAScog, brain mapping and transcranial Doppler ultrasonography, respectively. Patients receiving 360 mg/day of anapsos showed a significant improvement in cognitive performance after treatment (ADAScog scores: p < 0.05) that was not observed in patients treated with placebo or 720 mg/day of anapsos. As compared to placebo, anapsos (360 mg/day) induced a significant improvement in ADAScog scores in mild senile dementia patients (p < 0.01) and in the subset of patients with AD (p < 0.05). Anapsos (360 mg/day) also increased cerebral blood flow velocities in left and right middle cerebral arteries in the subgroup of AD patients, whereas with the dose of 720 mg/kg this increase was only observed in the left side. Patients treated with anapsos (360 mg/day) showed a decrease in relative delta power and an increase in relative theta and alpha brain bioelectrical activity frequencies, indicating an acceleration of the EEG pattern. The present results show that anapsos (360 mg/day) improves cognitive performance, cerebral blood perfusion and brain bioelectrical activity in patients with senile dementia. These effects of anapsos were more marked in demented patients with mild mental deterioration and/or with dementia of the Alzheimer type. PMID- 11196349 TI - When healers kill. Could better monitoring have stopped a homicidal doctor? PMID- 11196350 TI - Monkeying with nature. A genetically altered primate could aid the study of human disease. PMID- 11196351 TI - The ABCs of vitamin A. Veggies revisited. PMID- 11196352 TI - Optical cylinder designs to increase the field of vision in the osteo-odonto keratoprosthesis. AB - BACKGROUND: The single optical cylinders used in the osteo-odonto keratoprosthesis (OOKP) are known to produce very small visual fields. Values of 40 degrees are typically quoted. The purpose of this paper is to present designs for new optical cylinders that significantly increase the field of view and therefore improve the visual rehabilitation of patients having an OOKP. METHODS: Computer ray-tracing techniques were used to design and analyse improved one- and two-piece optical cylinders made from polymethyl methacrylate. All designs were required to have a potential visual acuity of 6/6 before consideration was given to the visual field and optimising off-axis image quality. Aspheric surfaces were used where this significantly improved off-axis image quality. RESULTS: Single optical cylinders, with increased posterior cylinder (intraocular) diameters, gave an increase in the theoretical visual field of 18% (from 76 degrees to 90 degrees) over current designs. Two-piece designs based on an inverted telephoto principle gave theoretical field angles over 120 degrees. Aspheric surfaces were shown to improve the off-axis image quality while maintaining a potential visual acuity of at least 6/6. This may well increase the measured visual field by improving the retinal illuminance off-axis. CONCLUSIONS: Results demonstrate that it is possible to significantly increase the theoretical maximum visual field through OOKP optical cylinders. Such designs will improve the visual rehabilitation of patients undergoing this procedure. PMID- 11196353 TI - True exfoliation of the lens capsule following uveitis. AB - PURPOSE: To report a rare case of true exfoliation of the lens capsule following panuveitis, with slit-lamp photographs before and following the development of the true exfoliation. METHODS: Case report. Review of the history and clinical features of a 70-year-old woman who developed true exfoliation during the treatment for panuveitis. RESULTS: After 7 months of treatment for bilateral panuveitis with topical steroid and tropicamide, the patient developed a thin, transparent membrane arising on the lens surface in the right eye. A diagnosis of true exfoliation of the lens capsule was made. CONCLUSIONS: True exfoliation of the lens capsule following uveitis may occur due to the weakening of the anterior capsule by metabolic disorder caused by uveitis and precipitated by repeated mydriasis. PMID- 11196354 TI - Retinal blood flow changes in diabetic retinopathy measured with the Heidelberg scanning laser Doppler flowmeter. AB - BACKGROUND: Investigation of retinal blood flow in patients with and without diabetic retinopathy (DR). Retinal blood flow is measured with the non-invasive Heidelberg Retinal Flowmeter (HRF). The clinical suitability of the HRF in patients with diabetes mellitus is investigated, and measured blood flow is compared with blood flow in a group of non-diabetic persons. METHODS: Cross sectional study of retinal capillary perfusion in eighty diabetic patients and forty-nine control persons, non-invasively measured with the Heidelberg scanning laser Doppler flowmeter. RESULTS: In the control group, HRF measurements could be performed in all subjects. In the diabetes group some patients had media opacities or were not able to maintain stable fixation. Therefore HRF measurement was only possible in 79%, 75% and 60% of the subjects for the nasal, papillo macular and foveal areas respectively. Retinal blood flow as measured in the perifoveal and nasal areas was associated with the level of diabetic retinopathy. In patients with proliferative DR (levels 4 and 5) the blood flow was reduced, in comparison with that of the patients with exudative or non-proliferative DR (levels 1 and 2) and preproliferative DR (level 3). Blood flow was not correlated with age, systemic blood pressure, intra-ocular pressure and perfusion pressure in either group. A significant negative correlation with the actual blood glucose level was found in the perifoveal area (R = -0.585, P = 0.0001). CONCLUSIONS: The HRF offers an interesting non-invasive method for measurement of retinal blood flow. In this cross-sectional study variations in retinal blood flow could be detected in various stages of DR in relation to clinically visible funduscopic changes. PMID- 11196355 TI - Phacoemulsification following treatment of choroidal melanoma. AB - BACKGROUND: Little is known about the risks, effects and results of phacoemulsification following treatment with different modalities of choroidal melanoma. METHODS: In a retrospective study, records were evaluated of 72 patients who underwent cataract surgery after treatment of choroidal melanoma (35 were treated with iodine-125 plaques, 27 with ruthenium-106 plaques, eight by tumor excision, and two with proton beam irradiation). The data were analyzed with respect to complications, effects on postoperative tumor care and visual outcome. RESULTS: Phacoemulsification was performed at a mean interval of 21.5 months after primary tumor therapy. An intraocular lens (IOL) was implanted in 93% of the cases. The mean postoperative follow-up time was 16.2 months. Preoperative problems were rubeosis iridis (30.5%), secondary glaucoma (34.7%) and posterior synechiae (41.6%). Intraoperatively, defects of the posterior capsule occurred in 12.5%. Visual acuity equal to or better than preoperative vision was found in 95.8% of the patients as the best postoperative measurement and in 72.2% at the last follow-up measurement. A deterioration of more than two lines in visual acuity was observed in 4.2% as the best postoperative vision and in 27.8% at the last documented examination. Phacoemulsification was not the cause of deterioration in any of the cases. After cataract surgery, tumor retreatment was necessary in 19.4%. Treatment of radiation retinopathy was performed for the first time in 13.8%. Metastases developed in six patients (8.3%). CONCLUSION: Phacoemulsification following treatment for choroidal melanoma is both possible and advisable. The majority of patients have enhanced visual acuity. No decrease of vision occurred as a result of cataract extraction. The postoperative care of intraocular tumors and the treatment of radiation retinopathy is improved by timely cataract surgery. PMID- 11196356 TI - The sensitivity and specificity of direct ophthalmoscopic optic disc assessment in screening for glaucoma: a multivariate analysis. AB - BACKGROUND: Previous studies have shown that the cup:disc (C/D) ratio has limited sensitivity and specificity. Improved sensitivity and specificity has been found with combinations of disc parameters using stereophotography or disc imaging, but the extent to which these studies reflect what can be achieved by direct assessment is unclear. The purpose of this paper is to report the sensitivities and specificities of a range of disc parameters, both in isolation and in combination, as graded during clinical examination with direct ophthalmoscopy. METHODS: Sixty-seven patients with newly diagnosed primary open angle glaucoma and 145 non-glaucomatous subjects were examined by direct ophthalmoscopy. The following features of the optic disc were graded: vertical and horizontal C/D ratios (uncorrected for disc size), narrowest rim width, presence/absence of disc haemorrhage, focal pallor of the neuroretinal rim, parapapillary atrophy, steepness of the cup-edge and presence/absence of baring of the lamina cribrosa. Subjects were validated as glaucomatous/non-glaucomatous on the basis of visual fields, independently of the results of optic disc gradings. Multiple logistic regression modelling was used to evaluate the effectiveness of combinations of disc parameters. RESULTS: Sensitivities and specificities are limited for all features when considered in isolation. The 'cupping' parameters have the highest sensitivities and specificities but no single cut-off criterion for these parameters has both high sensitivity and specificity. Multiple logistic regression modelling indicated that two disc parameters in combination, narrowest rim width and parapapillary atrophy, were independently associated with glaucoma and achieved best prediction. Combining information from these parameters achieved a sensitivity of 81% (95% CI = 69-89%) and a specificity of 90% (95% CI = 84-95%), a level of discrimination that is not significantly better than narrowest rim width alone in terms of area under the receiver operator characteristic (ROC) curve. CONCLUSION: Disc assessment during clinical examination with direct ophthalmoscopy can achieve comparable sensitivities and specificities with those previously reported for stereophotographic assessment or visual fields screening. However, since the diagnostic accuracy of disc assessment in isolation is inadequate for screening, a combined test strategy is necessary. PMID- 11196357 TI - Light-induced damage of the retina through slit-lamp photography. AB - BACKGROUND: I report on two patients who suffered severe loss of visual acuity after slit-lamp photography of the anterior eye segment. METHODS: Both patients were pseudophakic and pictures were taken to document the degree of posterior capsule opacification via retroillumination with dilated pupils. Both patients had excellent visual acuity at the time of photography was taken and experienced reduction of to hand movement afterwards. A Zeiss 75 SL device was used for the slit-lamp photography. In cooperation with Carl Zeiss Jena the slit lamp was investigated. RESULTS: Ophthalmoscopy and angiography after photography discovered a central macular defect, similar to a photocoagulation. The visual acuity did not recover. CONCLUSION: Under certain circumstances slit-lamp photography of the anterior eye segment can lead to severe light-induced damage of the retina. PMID- 11196358 TI - Changes of retinal capillary blood flow in age-related maculopathy. AB - BACKGROUND: To investigate retinal capillary blood flow characteristics in patients with age-related maculopathy (ARM). METHODS: Retinal capillary blood volume (VOL), blood flow (FLOW), and velocity (VEL) were measured in four macular sectors (I, II, III, IV) and in two areas beyond the temporal superior and inferior major vessel arcades (V and VI) in: 10 eyes with early ARM (drusen > or = 63 microns and/or atrophy of the retinal pigment epithelium, RPE, < 175 microns and/or proliferation of RPE), 13 with late ARM (exudative), 10 with late ARM (fibrotic), 14 normal eyes of 14 children of patients with ARM, and in 4 age- and sex-matched control groups using the Heidelberg retinal flowmeter (HRF). Statistical analysis was performed with the exact Wilcoxon test using an additional adjustment procedure by Bonferroni-Holm. RESULTS: As compared to the control group, there was no significant change of VOL, FLOW, and VEL in patients with early ARM. In patients with late ARM (exudative), there was a significant higher FLOW in sectors I, II, and IV and a higher VOL and VEL in sectors III and IV. The group with late ARM (fibrotic) showed a reduction of VOL and FLOW in sectors I-IV and of VEL in sectors II and IV. In children of ARM patients, VOL, FLOW, and VEL of sectors I-VI did not differ from the control group. CONCLUSION: HRF measurements in patients with ARM indicate an increased macular retinal capillary blood flow in patients with the exudative form of late ARM and a decreased macular perfusion in those with the fibrotic form. PMID- 11196359 TI - Longitudinal nerve fibre layer thickness change in normal-pressure glaucoma. AB - PURPOSE: To investigate longitudinal retinal nerve fibre layer (RNFL) thickness change in patients with normal-pressure glaucoma (NPG) and to assess how this may be related to visual fields. METHODS: NPG patients and normal subjects who had had serial GDx nerve fibre layer Analyzer II imaging and Humphrey visual fields performed at least 18 months apart were selected for study. These measurements were compared between groups at baseline and at subsequent follow-up, for change over time. RESULTS: Seventy-five NPG patients and 35 normal subjects were studied. Significant differences in RNFL thickness were found between NPG patients and normal controls at baseline (P < or = 0.001). Over the same time, there was greater RNFL thinning in NPG patients than in normal subjects (P < or = 0.0001). RNFL thinning in NPG was negatively correlated with visual field log MD at baseline (P < 0.001) and change in MD over time (P < 0.001). CONCLUSION: Reduction of RNFL thickness over time was significantly greater in NPG patients than in normal subjects, indicating that NPG patients' RNFL had thinned at a faster rate. NPG patients with initially better visual fields had a greater reduction in RNFL thickness than did those with initially more advanced visual field defects, suggesting that more RNFL change may be observed when glaucoma is at an earlier stage. There was a direct relationship between RNFL thinning and visual field deterioration. PMID- 11196360 TI - Morphological study on rupture of posterior capsule in RLC mouse lens. AB - PURPOSE: To clarify the causative factor underlying rupture of the posterior capsule of the RLC mouse lens as a recessive trait around the 50th postnatal day. METHODS: The lenses of the RLC mouse were removed in the period from birth to 50th postnatal day. Some specimens were observed by light microscopy and transmission and scanning electron microscopy. Others were examined as flat preparations of the lens epithelium. RESULTS: There was an abnormal arrangement of lens fibers at the newborn stage, and lens fibers of the perinuclear zone ended almost vertical in relation to the posterior capsule. Consequently, the posterior suture was not formed in this mouse lens. On the 10th postnatal day, the ends of the lens fibers that terminated in the posterior capsule became swollen, and the posterior capsule at the posterior polar region became thin. On the 20th day, the area of swollen fibers was so large at the center of the posterior capsule that a vacuolated area was observed under the dissecting microscope. On the 30th day, the posterior cortical fibers in this area showed marked swelling, and the posterior capsule became extremely thin. On the 40th day, the anterior cortex became unusually thick, and the lens nucleus was dislocated towards the posterior capsule. On the 50th day, the posterior capsule ruptured. At this time the lens fibers from the perinuclear zone constituted the central area of rupture, and the cortical fibers from the equator formed the protruded area outside the lens. CONCLUSION: The findings revealed that the RLC mouse lens has an abnormal lens fiber arrangement from the early period of lens development, that the lens fibers from the perinuclear zone cause swelling without forming the posterior suture, and that the thin capsule is ruptured by pushing out of the nucleus by thickening of the anterior cortex. PMID- 11196361 TI - Transplantation of iris pigment epithelium into the choroid slows down the degeneration of photoreceptors in the RCS rat. AB - BACKGROUND: Trophic factors [e.g. basic fibroblast growth factor (bFGF)] released by transplanted retinal pigment epithelial (RPE) cells are able to slow down the hereditary degeneration of the retina in the Royal College of Surgeons rat in sites distant from the site of transplantation where rod outer segment (ROS) phagocytic activity is not reconstituted by the transplants. METHODS: To investigate whether iris pigmented epithelial (IPE) cells are also able to generate this rescue by trophic factors, we transplanted IPE cells from Long Evans rats into the choroid and subretinal space of 17 young RCS rats. The eyes were enucleated after 6 months and prepared for light microscopy. Six age-matched RCS rats served as controls. Light microscope sections from the whole choroid, healthy choriocapillaris, transplanted cells and the maximum thickness of the choroid, and outer nuclear layer parameters were analyzed by computer-assisted morphometry. RESULTS: In transplanted animals photoreceptor cells were rescued from degeneration although the majority of the transplanted IPE cells were located in the choroid. In the non-transplanted group photoreceptors were absent. CONCLUSIONS: Transplantation of IPE cells slows down degeneration of the photoreceptors in the RCS rat. This photoreceptor-sparing effect by the IPE cells was observed even when the transplants were predominantly located within the choroid. The beneficial effect observed may be related to trophic factors possibly secreted by the transplanted IPE cells. PMID- 11196362 TI - Alterations of sensory retinal explants exposed to choroidal melanoma cells ex vivo. AB - BACKGROUND: Cultures of retinal explants have been established as a useful tool to investigate effects of pathogenic agents in vitro. We used such cultures as a model to study the effects of choroidal melanoma on retinal organisation and function. METHODS: Rabbit retinal explants were co-cultured with human choroidal melanoma cells, or exposed to supernatants from choroidal melanoma cell cultures, for various periods from 1 day to 10 days. The retinal explants were then studied by histology and immunocytochemistry for glial fibrillary acidic protein (GFAP) and vimentin. The release of the pro-inflammatory interleukins IL-6 and IL-8 into the media was measured by enzyme-linked immunosorbent assay. RESULTS: Both in the co-cultures and after treatment with choroidal melanoma cell supernatants for more than 1 week, the layered structure of the retinae became disorganised. Retinal glial (Muller) cells displayed gliosis as indicated by increased GFAP immunoreactivity and decreased immunoreactivity for vimentin. Additionally, the secretion of cytokines, particularly of IL-8, was significantly modulated. The retinal explants produced much less IL-8 than the melanoma cells in separate cultures but increased their IL-8 release significantly after a few days' exposure to melanoma cell-conditioned medium. CONCLUSION: The results show that in cases of choroidal melanoma, the well-known morphological and inflammatory alterations of the retina are accompanied by glial cell reactivity and up regulated retinal cytokine secretion, and may be caused by soluble factors secreted and induced by the melanoma. PMID- 11196363 TI - Transforming growth factor-beta: a growth factor inducing alpha B-crystallin expression in ciliary muscle cells. AB - BACKGROUND: In a recent study we showed that, in vitro, transforming growth factor-beta 2 (TGF-beta 2) induces alpha B-crystallin expression in cultured trabecular meshwork (TM) cells, but not in cultured fibroblasts. We assumed that alpha B-crystallin can be induced by TGF-beta 2 only if the cells are already expressing a basal level of the protein. In the present study we therefore treated cultured ciliary muscle (CM) cells constitutively expressing alpha B crystallin and investigated the effect of TGF-beta on expression of alpha B crystallin and the corresponding mRNA in these cells. MATERIAL AND METHODS: Monolayer cultures of third-passage CM cells from eyes of five human donors (12 73 years), being confluent for 7 days, were treated with 1.0 ng/ml TGF-beta 1 or TGF-beta 2. Induction of alpha B-crystallin and the related mRNA was investigated by immunofluorescence and by western and northern blot analysis. RESULTS: An increase in alpha B-crystallin mRNA was observed following treatment with TGF beta. Actinomycin blocked the induction of alpha B-crystallin by the cytokine TGF beta. Using western blotting the increase in alpha B-crystallin expression in CM cells was only small. CONCLUSION: These results confirm our assumption that induction of alpha B-crystallin by the cytokine TGF-beta depends on basal levels of the protein and its mRNA constitutively present within the cells. Comparison of the increase in alpha B-crystallin mRNA and protein expression indicate that post-transcriptional regulation mechanisms are responsible for these findings in CM cells. PMID- 11196364 TI - Neurotransmitter contents in the retina of RCS rat. AB - BACKGROUND: Retinitis pigmentosa is a hereditary disease characterized by gradually developing degeneration of photoreceptors. The Royal College of Surgeons (RCS) rat is an experimental model of retinitis pigmentosa. However, there is a paucity of information concerning neurotransmitter contents in the retina of RCS rats. Thus, we determined the retinal contents of neurotransmitters in RCS rats at 4 and 23 weeks postnatally and in age-matched congenic control rats. METHODS: Dopamine (DA) and acetylcholine (ACh) were electrochemically measured by high-performance liquid chromatography (HPLC). Neuroactive amino acids, including gamma-aminobutyric acid (GABA) and taurine, were determined by means of an HPLC-precolumn derivatization method. RESULTS: Contents of DA, ACh, glutamate, aspartate and GABA in the retina of RCS rats 4 weeks postnatally were within normal ranges. At 23 weeks, the retinal contents of DA, glutamate and aspartate in the RCS rats were significantly lower than in the age-matched control rats, while the contents of ACh and GABA were unaffected even at this later stage. On the other hand, the retinal content of glycine in the RCS rats at 23 weeks was significantly higher than that in the age-matched control rats. It is interesting to note that the content of taurine in the RCS rats had already decreased at 4 weeks postnatally and the decrease was more marked at 23 weeks. CONCLUSION: The decrease in taurine content is probably the first sign of degeneration revealed by the retinal neurotransmitters of RCS rats. PMID- 11196365 TI - [Is knee osteotomy still indicated in knee osteoarthritis?]. AB - This study was undertaken to investigate whether high tibial osteotomy (HTO) still had a role in the treatment of osteoarthritis of the knee joint. The author has performed photoelasticity studies which confirmed abnormal stress distribution over the joint, as soon as its mechanical axis was deviated and the joint line had an obliquity over 10 degrees. High tibial osteotomy to correct varus or valgus deformity restores a symmetrical stress distribution and represents the only etiological treatment of secondary osteoarthritis of the knee. Two hundred and fifty HTO's were performed between 1971 and 1985 for osteoarthritis of the knee. The short-term result was good or very good in 75%, fair in 20% and poor in 5%. Fair and poor results were related to insufficient correction, to infection or mostly to incorrect indications. In 152 cases with a good or very good short term result, a further evaluation was made between 8 years and 15 years after operation. It was noted that osteoarthritis had been arrested in 105 cases (69%) whereas it had deteriorated in 47 cases. The main factors associated with further deterioration were insufficient correction and persistence of joint line obliquity. Provided on optimal correction is achieved (3 degrees to 6 degrees hypercorrection in valgus osteotomy, 0 degree in varus osteotomy) and provided a horizontal joint line is restored, HTO performed in good indications (Ahlback grade I or II) may provide good results for at least 10 to 15 years. PMID- 11196367 TI - [The role of arthroscopy in subacromial pathology. Retrospective study of a series of arthroscopic acromioplasties]. AB - The authors report the results of a retrospective study of 59 arthroscopic acromioplasties. Objective shoulder assessment was made following the relative Constant score and UCLA rating scale. Subjective satisfaction of the patient was assessed on an analogic scale. The patients were divided into 3 groups, according to the subacromial pathology treated. The first group (27 shoulders in 23 patients) included patients with subacromial impingement without a complete rotator cuff tear. The objective result, between 80 and 90%, was close to results in others series reported. Distinction between patients with no tear or partial tear of the cuff showed better results for patients with partial tears. This surprising finding may be at least partially explained by the fact that these patients were older than those without a cuff tear. The results of this study, and the review of the literature, confirmed the value of subacromial decompression as a treatment for impingement without complete cuff tear resistant to at least 6 months of conservative treatment; comparison between surgical and arthroscopic series showed similar results. The second group (19 shoulders in 19 patients) included patients with impingement and complete cuff tear. The objective results and the literature review led us to specify indications. Subacromial decompression with debridment of the tear has given excellent results in older patients--over 60 for most authors--when the tear was limited. In our study, the function of the shoulder at revision was good when the tear was limited to the supraspinatus and part of the infraspinatus. The third group (13 shoulders in 10 patients) included patients with calcifying tendinitis. Arthroscopic acromioplasty was performed in every case; excision of the calcification was performed in less than half of the cases and did not influence the final result. The calcifications had disappeared at revision in all cases. This may suggest that the treatment of the associated impingement was the most important procedure in these cases. PMID- 11196366 TI - The CINCA syndrome: a rare cause of chronic arthritis and multisystem inflammatory disorders. AB - Chronic infantile neurological cutaneous articular (CINCA) syndrome is a rare disorder with neonatal onset characterised by a chronic progressive inflammatory process with skin rash, articular and central nervous system involvement. This primary systemic inflammatory disorder should be distinguished from juvenile rheumatoid arthritis (JRA). Although the articular findings are characteristic features of CINCA syndrome, there is a certain degree of variability in the articular involvements which are not always symmetrical nor is the degree of severity uniform. The etiology of CINCA syndrome remains unknown. No single treatment has been found to be effective. This syndrome is known in the American medical literature as infantile onset multisystem inflammatory disease (IOMID). PMID- 11196368 TI - Lateral epicondylalgia: treatment by manipulation under anaesthetic and steroid injection and operative release. AB - A retrospective study of 112 cases of lateral epicondylalgia treated between April 1995 and April 1998 was conducted. The treatment modalities included manipulation under anaesthetic and operative release. A questionnaire was used to assess the outcome. The patients who were unresponsive to conservative treatment either had manipulation under anaesthetic and a steroid injection or had an operative release. Those who had manipulation under anaesthetic and injection had 33.3% satisfactory outcome for pain and function at 17.2 months mean follow-up. Among those who had operative release, 69% had satisfactory outcome for pain and function at 17.2 months mean follow-up. The results of manipulation under anaesthetic and steroid injection are not good enough for this treatment to be recommended in the management of tennis elbow. It is more effective to treat the patients unresponsive to conservative treatment with open release. PMID- 11196369 TI - Clinical relevance of acetabular erosion in young patients with a bipolar hip prosthesis. AB - In elderly patients bipolar hip prostheses are often used for intracapsular fractures of the femoral neck and are often complicated by pain after a few years; this pain is frequently related to acetabular erosion seen on xray. In this study 18 bipolar hip prostheses were used in the treatment of a proximal femoral sarcoma in a young patient population (mean age: 39.6 years). Their quality of life was evaluated by TESS and MSTS scores, after a mean follow-up of 81.8 months (range 8-171 months). A radiologic grading system was used to assess acetabular erosion on plain xrays. The patients did not report significant pain, they enjoyed a very good quality of life, and they did not show any obvious acetabular erosion. The use of a bipolar implant appears as a good alternative to total hip replacement in the treatment of relatively young patients who have to undergo proximal femoral tumor resection procedures and have a normal acetabulum. PMID- 11196370 TI - Impaction grafting for acetabular deficiency in total hip arthroplasty for developmental hip dysplasia. AB - The pathological anatomy in neglected developmental dysplasia of the hip often demands some sort of reconstructive surgery to augment the acetabular bone stock during total hip arthroplasty. We have reviewed 11 hips in 10 patients with osteoarthritis secondary to developmental hip dysplasia who underwent cemented total hip arthroplasty using impaction grafting of the acetabulum with a morselized femoral head autograft, to bring the socket down to the anatomical hip center. The mean age at the index procedure was 43.4 years (ranging from 29 to 60 years) and the mean follow-up period was 3.8 years (ranging from 2 to 7 years). Postoperative functional evaluation according to the Merle d'Aubigne and Postel score modified by Charnley revealed very satisfactory results. Radiographic review showed incorporation of all grafts. One socket is radiographically loose. No major complications have been encountered. There have been no reoperations. We believe that acetabular impaction grafting is a valuable alternative in dealing with osteoarthritic hips secondary to developmental hip dysplasia. PMID- 11196372 TI - Conservative or surgical management of distal femoral fractures. A retrospective study with a minimum five year follow-up. AB - We report the outcome of conservative and surgical management in 50 skeletally mature patients (average age 64.6 years, 36 females patients) with 51 supracondylar femoral fractures treated in our unit between June 1991 and December 1993. Thirty-six fractures were caused by low-energy trauma, and 15 were due to high-energy trauma. Open fractures occurred in 5 patients. Of the 34 patients (35 fractures) treated conservatively, 15 (46%) achieved a satisfactory result. Of the 16 patients treated by internal fixation, 10 (62%) reached a satisfactory outcome. Osteoporosis, severe comminution of the fracture, involvement of the knee joint, and soft tissue injury in open fractures were associated with unsatisfactory results. Conservative management of these fractures is associated with a lesser chance of achieving a good functional result. With the advent of new fixation devices and our experience that conservative management can actually lead to many complications, the proportion of patients operated upon is likely to increase. PMID- 11196371 TI - Failure of total hip arthroplasty with Boneloc bone cement. AB - Early failure of Boneloc cemented total hip arthroplasty is well documented. However, information regarding the long term prognosis is scanty. The aim of this study was therefore to assess the long term failure rate of total hip replacement with Boneloc bone cement. Between January 1991 and March 1992, Boneloc bone cement (Polymers Recontructive A/S, Farum, Denmark) was used in 42 consecutive total hip replacements in 42 patients. The average age of the patients was 75 years. There were 25 women and 17 men. The diagnosis at operation was osteoarthritis in all cases. A cemented Muller Taperloc femoral stem was used with a cemented Muller acetabular cup (Biomet, Warsaw, USA). The follow-up time was 9 years. All patients underwent radiographic control the first postoperative year and annually after 1995. To date 21 patients have been revised for aseptic loosening at a mean of 5 years (range: one year to 8 years). Three other patients have definite radiographic evidence of loosening. The overall failure rate is therefore 24/42 = 57%. Our results confirm the previously reported poor results of Boneloc bone cement for hip arthroplasty and support the recommendation of indefinite follow-up for surviving prostheses. New prosthesis designs and new cements should have documentation, including laboratory tests and randomized clinical studies with radiostereometric evaluation. However, the ethical responsibility rests heavily on the shoulders of the clinician to make a correct analysis of the need for a new product before he begins to use it. PMID- 11196373 TI - Anterograde femoral nailing with a reamed interlocking titanium alloy nail. AB - Intramedullary nailing has become the gold standard for treatment of femoral diaphyseal fractures. Between March 1995 and December 1998 we performed 40 intramedullary nailings using the ACE femoral nail (De Puy). The patients were followed for an average of 27.9 months (range: 6-54 months). The mean age was 33.2 years (range: 17-87 years); the sex distribution was 33 males and 7 females. All fractures were unilateral (right 18, left 22). Most of the fractures were caused by traffic accidents (35), the others originated from sports, work and gunshot (1). Thirty-five fractures were closed and 5 were open: 1 was grade I, 2 were grade II and 2 grade IIIa according to Gustilo's classification. According to the AO classification 18 fractures were type A, 13 type B and 9 type C. The majority of patients had associated injuries: neurotrauma 2, chest trauma 2, and other fractures e.g. of the clavicula, lumbar spine, patella, tibia. Immediate surgery was performed in 34 cases, delayed surgery in 6 cases. All fractures were treated on a fracture table, with closed reduction, reaming of the intramedullary canal, proximal and distal locking and intraoperative control of rotation and length. The mean time to healing was 17.85 weeks (range: 18-50 weeks). The following complications were observed: 3 delayed unions, which united after dynamisation, one malunion, which required corrective osteotomy, and one nonunion, which healed after exchange nailing. We encountered no rotational deformity and no clinically relevant shortening. Six nails were removed due to irritation by locking screws. These results are comparable with those of larger series in the literature with other types of interlocking nails. The union rate in this series was 97.5%. PMID- 11196374 TI - Ganglion cysts associated with cruciate ligaments of the knee: a possible cause of recurrent knee pain. AB - Intraarticular ganglia of the knee are uncommon; however, these ganglion cysts may produce knee discomfort without a clear etiology. We present the cases of 10 patients with ganglion cysts arising from cruciate ligaments of the knee joint who underwent arthroscopic excision after MR examination. The MR findings, clinical features and arthroscopic findings were evaluated comparatively. Diagnoses were confirmed by means of a histological study after arthroscopic excision. The cysts were fluid-filled, with low T1-weighted signal intensity and high T2-weighted signal intensity. Except for two patients with recent accidents, the remaining eight presented chronic pain without any history of trauma. Pain was the most frequent clinical sign. It was associated with knee extension in 3 cases and with flexion in 3 cases. In 7 cases, cysts were exclusively associated with the anterior cruciate ligament (ACL). Only in one case was a cyst associated with an ACL rupture. Four patients presented meniscal lesions. All ganglia appeared solitary in each knee. Postarthroscopy evolution was painless in 8 patients. Histologic diagnoses corresponded to ganglion cysts. The tissues from the patient with the ACL rupture presented a fibrous reaction with myxoid degeneration forming intraligamentary ganglion cysts. PMID- 11196375 TI - Surgical risk factors in Larsen's syndrome. AB - The authors report on a child with typical Larsen's syndrome with some rare findings such as mixed-type hearing loss and with some potentially fatal operative risks including laryngomalacia and cervical instability. A few deaths with Larsen's syndrome have been reported associated with various fatal risks such as spinal instability. Therefore, laryngomalacia and several other potentially fatal risks are presented in this report as awareness may prove essential to orthopedic surgeons. PMID- 11196376 TI - Congenital bilateral short femur complicated by stress fracture. A case report. AB - Congenital malformation of the femur is an uncommon but complex problem. Short femur with proximal deficiency (Kalamchi type III) is part of this congenital anomaly. If the precautions associated with progressive coxa vara and bowing in the femoral shaft are not taken, stress fractures may occur in the femoral neck and the femoral shaft. We report on a 38-year-old female with type III-A congenital malformation of both femurs who presented the complications mentioned and had not been treated before. This case is instructive because it illustrates the complications developed in patients who have not been treated. PMID- 11196377 TI - Extradigital glomus tumor causing para-Achilles tendon pain. A case report. AB - A 48-year-old woman with a 15-year history of a painful nodule in the para Achilles tendon area was evaluated by clinical examination, magnetic resonance imaging and ultrasonography, then treated by simple surgical excision of the nodule. Pathology revealed a glomus tumor, which is extremely rare in the para Achilles tendon area. This is the first report of a glomus tumor in this location. PMID- 11196378 TI - High-grade metachronous osteosarcoma. A case report over a 23-year period. AB - This is a case report on the remarkable 23-year course of a metachronous osteogenic sarcoma in a 31-year-old man. Histology invariably showed the features of a high-grade osteogenic sarcoma with predominantly chondroblastic cells. During the observed period the patient developed nine osseous metastases. The quiescent clinical course of some metastases was in sharp contrast to the histological pattern. The patient finally died from symptoms of increasing cervical spinal cord compression without ever developing lung metastases. PMID- 11196379 TI - [Traumatic luxation of the posterior tibialis tendon]. AB - Anterior dislocation of the tibialis posterior tendon is a traumatic lesion, which is rarely suspected following ankle trauma. It seems to be promoted by hypoplasia of the retromalleolar sulcus. Surgical treatment is easy and reportedly gives excellent results, but the diagnosis is difficult and absence of diagnosis may result in functional instability of the foot requiring more invasive surgical treatment. PMID- 11196380 TI - [Isolated traumatic luxation of the distal radio-ulnar joint. A case report]. AB - The author reports a case of isolated traumatic volar dislocation of the ulnar head in the distal radioulnar joint. This fairly uncommon injury is seldom accurately diagnosed at first presentation because there is no distinct deformity at the wrist and extension-flexion is normal and painless. However pronation is always restricted and painful. A dislocation of this joint may be simple or complex and the treatment varies accordingly. Because the dislocation in this patient had occurred more than two months previously, surgical reduction failed and resection of the distal ulna using Darrach's procedure was performed. PMID- 11196381 TI - [Donation and transplantation in Spain at the end of the 20th century]. PMID- 11196382 TI - [Stromal tumor of the rectum and leiomyosarcoma of the prostate as a cause of urinary syndrome attributable to BPH]. AB - OBJECTIVE: To discuss the classifications of patients with lower urinary tract symptoms ascribed to BPH, in order to define the indication for treatment for patients with similar features but of a different etiology. The literature is also reviewed. METHODS/RESULTS: Two patients, aged 62 and 63 years, diagnosed as having BPH were found to have a gastrointestinal stromal tumor (GIST) and a leiomyosarcoma of the prostate, respectively. The first patient had undergone retropubic resection. Frozen section analysis revealed a GIST. The second patient had undergone TURP twice. A perineal biopsy at the last medical examination showed a leiomyosarcoma of the prostate. This patient finally underwent pelvic tumorectomy. The international classification of BPH is discussed: PQSF (P: prostatic weight determined by transrectal US or DRE; Q: quality of life assessment; S: international prostate symptom score (IPSS); F: maximum urinary flow rate by uroflowmetry--Qmax). CONCLUSIONS: The classifications are practical, but should be improved. In our view, details useful in orienting the diagnosis could be lost by oversimplification. PMID- 11196383 TI - [Deletion of ABH antigens in urine sediment cells from patients with prostatic adenoma]. AB - OBJECTIVE: This study was conducted to analyze ABH antigenic expression in urinary sediment of patients with benign prostatic hyperplasia (BPH) before and after deobstructive surgery. METHODS/RESULTS: The agglutination inhibition technique was utilized to determine the ABH antigenic expression in urinary sediments of 30 healthy subjects and 34 patients with BPH. The presence of neoplastic cells was also determined in urinary sediments of the patients by Papanicolaou's stain. These studies were performed before and 12 months after surgery. Membrane antigen expression was found in 100% of the healthy subjects and in only 50% of the patients with BPH before surgery. Only 25 patients returned for control evaluation after surgery. Of these, 17 were positive and of the remaining 8 patients who were negative preoperatively, only one continued to be negative. Urine cytology demonstrated progression to malignancy in this patient. CONCLUSIONS: Determination of ABH antigenic expression appears to be able to identify premalignant conditions and could be a useful complementary diagnostic method to cytology. PMID- 11196384 TI - [Usefulness of PSA-complex in the diagnosis of prostatic carcinoma]. AB - OBJECTIVE: Since its discovery as a marker for prostate cancer, there have been many attempts to enhance the diagnostic efficacy of the prostate specific antigen (PSA). Among these are the studies that analyze the behavior of different forms of serum PSA bound to different antiproteases, such as alpha-1-antichymotrypsin, which forms the complexed PSA (PSA-c). This study analyzed the utility of PSA-c to enhance specificity without altering sensitivity in comparison to total PSA (PSA-t). METHODS: From September 1998 to March 1999, blood samples were obtained from 96 patients that had undergone a prostate biopsy due to a suspicion of prostate cancer. PSA-c, PSA-t (Technicon Immunol system, Bayer) and PSA-c/PSA-t ratio were analyzed in these patients. RESULTS: ROC curves were plotted and the optimal cutoffs were found for which the specificity was higher for PSA-c (44.6% [CI 95%, 32-57]) versus PSA-t (35.4% [CI 95%, 25-49]) and the PSA-c/PSA-t ratio (38.5% [CI 95%, 27-51]) while maintaining a similar sensitivity index (90%). PSA c showed similar results for other values of sensitivity. CONCLUSIONS: PSA-c was found to improve specificity in comparison to PSA-t and PSA-c/PSA-t ratio. PSA-c determination could avoid unnecessary biopsies without altering sensitivity; i.e., the same number of prostate cancers will be detected. PMID- 11196385 TI - [Significance of random biopsies of healthy mucosa in superficial bladder tumor]. AB - OBJECTIVE: To analyze the characteristics of the random biopsies of normal appearing mucosa taken during TUR of superficial bladder tumors and to correlate them with the outcome and characteristics of the superficial tumor. METHODS: Multiple random biopsy specimens from normal-appearing areas of 300 TUR procedures for primary or recurrent superficial urothelial carcinoma were analyzed. Preoperative cytologies were obtained in most of the patients and tumor number, localization, size, stage and grade according to the WHO classification were determined. In patients with multiple tumors, the stage, size and grade of the worst tumor were utilized. Patients who showed a risk of recurrence during follow-up received intravesical therapy postTUR of the bladder. The site and characteristics of recurrence were analyzed and compared with the random biopsy findings. RESULTS: In 38 superficial tumors (12.7%), significant histological changes were found in the random biopsies of normal-appearing mucosa taken during resection. A significant difference was found between patients with and without positive random biopsies only for tumor stage. Statistically significant differences were found when comparing the primary and recurrent tumors, due to the greater number of high and moderate grade tumors in the primaries. There were significant differences in regard to the positive preoperative cytologies between the patients with negative and those with positive random biopsies. No statistical correlation was found between the localization of the superficial tumor and a positive biopsy or between the latter and the site of tumor recurrence. There were 126 recurrences (42%); mean time to recurrence was 13.5 months (median 9.5 months). No significant difference was found (log-rank) for time to recurrence in patients with positive or negative random biopsies, but significant differences were found when we analyzed the number of superficial tumors and the use of intravesical therapy, but not for the type of therapy. CONCLUSIONS: Multiple random biopsies permit a better categorization of the tumor and complete staging. The outcome and the decision to administer intravesical therapy following TUR of the bladder are influenced by the foregoing. The practical results of random biopsies, however, are scanty, since the prognostic significance of the histological changes found in these biopsies is not worse than that of the superficial tumor resected. There are, however, a few cases with a higher risk of recurrence and/or progression than the superficial tumor. Preoperative cytology is useful in the selection of these patients. Furthermore, since the proportion of high grade tumors is higher in primary tumors, performing multiple biopsies is mandatory in these cases if previous urine cytology is not available. PMID- 11196386 TI - [Epidermoid carcinoma of the penis]. AB - OBJECTIVE: To analyze our series and review the prognostic factors in the treatment of epidermoid carcinoma of the penis. METHODS: Age, time to consultation, circumcision, form of presentation, local treatment, tumor stage and grade, lymph node involvement and outcome were analyzed in 27 cases of carcinoma of the penis diagnosed at our hospital from 1981 to 1999. RESULTS: The incidence rate was 1.8 cases/100,000 men/year. No patient had been circumcised, except one who was circumcised in the adult age. The median time to consultation was 24 months (interquartile range: 60-7.75). The median follow-up was 37 months (interquartile range: 84-12). All patients with pT1GI-II and pT2G-II primary tumor (n = 21; 78% of the series) and with no lymphadenopathy were disease-free at 6 months' minimum follow-up [17 of the 21 patients (81%) had more than 32 months' follow-up]. Only one patient with pT1-GII tumor, but with a vertical growth pattern, had positive inguinal lymph nodes (pN2). The remaining patients with lymph node involvement showed infiltration of the erectile tissue and moderately or poorly differentiated tumors. Only two prophylactic lymphadenectomy procedures were performed (pN0). Regardless of treatment, 5 of the 6 patients with lymph node involvement died within one year after diagnosis. CONCLUSIONS: Given the demonstrated relationship between carcinoma of the penis and hygiene, and phimosis which makes hygiene difficult, circumcision should be performed in childhood. Furthermore, circumcision at this age has been demonstrated to have a prophylactic value that disappears in the adult age. PMID- 11196387 TI - [Partial nephrectomy in lithiasis]. AB - OBJECTIVE: To analyze our series of patients with renal lithiasis who underwent partial nephrectomy from 1980-1999. METHODS: 28 patients who underwent partial nephrectomy were analyzed (22 females; mean age 48.09 years, and 6 males; mean age 60 years). Surgery for lithiasis had been previously performed in 5 renal units. Nine patients had previously undergone ESWL (more than 3 sessions), all of whom subsequently developed multiple residual calculi. Twelve patients had a microbiologically confirmed positive urine culture. The renal lithiasis amenable to treatment by partial nephrectomy was frequently localized in the lower calyces (17 cases). RESULTS: Histopathological analysis of the nephrectomy specimen showed a prevalence of signs of chronic parenchymal atrophy (25 cases). Three cases showed segmental renal dysplasia (those in whom a superior heminephrectomy was performed for duplex excretory system). Fifty percent of the stone fragments analyzed showed calcium phosphocarbonate. Eight patients had postoperative complications; the most important were two cases of renal cutaneous fistula and one subphrenic abscess. At 9 1/2 years' mean follow-up, renal function is normal in 25 patients. Lithiasis developed in the contralateral unit in 6 cases and in the same renal unit in one case. CONCLUSIONS: Partial nephrectomy continues to be a therapeutic option for lithiasis. Its indication depends on the morphological and functional characteristics of the compromised renal unit, especially in those cases in whom renal preservation can be obviated due to its scanty significance. PMID- 11196388 TI - [Treatment of erectile dysfunction with vacuum devices]. AB - OBJECTIVE: To analyze the results achieved with vacuum devices in the treatment of erectile dysfunction. METHODS: A telephone survey was conducted on 150 patients undergoing treatment with a vacuum device. Of these, 89 responded; 79 of which were considered valid for the study. The duration and frequency of use, side effects and degree of patient and partner satisfaction were analyzed. Mean follow-up was 59.5 months. RESULTS: There were 14 dropouts early in the course of treatment. The remaining 65 patients used the device for a mean duration of 34.6 months, 3.7 times monthly. 63.3% of the patients achieved erection in more than half of the attempts. The most frequent side effects were pain (27 patients) and ecchymosis (7 patients). Forty-eight patients discontinued treatment at 10.8 months' mean follow-up. The most common causes for discontinuing treatment were lack of efficacy, refusal of the partner and pain. CONCLUSIONS: Treatment of erectile dysfunction with the vacuum constriction device should be utilized as an alternative to intracavernosal drug-induced erection therapy when oral therapy fails or is contraindicated. A male with a stable partner and impotence arising from venous leakage or mild cavernous artery insufficiency is the ideal candidate. PMID- 11196389 TI - [Scrotal invasive angiomyofibroblastoma. First reported case]. AB - OBJECTIVE: To report a case of locally invasive angiomyofibroblastoma of the scrotum. To our knowledge, this is the first case of invasive scrotal angiomyofibroblastoma reported in the literature. METHODS: A case of invasive angiomyofibroblastoma of the scrotum is presented. The literature is reviewed with special reference to the etiopathogenesis, clinical features, diagnosis and treatment of this rare soft tissue tumor. RESULTS/CONCLUSIONS: The case described herein shows that angiomyofibroblastoma can be invasive. PMID- 11196390 TI - [Foreign body as renal pseudotumor in a patient with renal polycystic kidney]. AB - OBJECTIVE: To report a case of granuloma due to a retained surgical sponge that mimicked a pseudotumor in a patient with autosomal dominant polycystic kidney disease. The appearance of retained surgical sponges on diagnostic imaging is reviewed. METHODS: Patient evaluation included renal ultrasound, magnetic resonance imaging (MRI) and arteriography. RESULTS: MRI provides characteristic features that permit preoperative diagnosis. CONCLUSIONS: In the presence of a mass or abscess in patients who have previously undergone surgery, a retained surgical sponge should be included in the differential diagnosis. MRI permits preoperative diagnosis. PMID- 11196391 TI - [Bilharziasis, clinical course of the disease: acute and chronic phase. Two clinical cases]. AB - OBJECTIVE: To report two cases of bilharziasis and review the literature with special reference to treatment according to the stages of the disease. METHODS/RESULTS: Two patients that had previously visited endemic areas consulted for hematuria and renal colic, respectively. One patient was in the acute stage of the disease. Diagnosis was made on the demonstration of eggs of the schistosome in urine. Good response was achieved by medical treatment. The other patient was in the chronic stage. No eggs were demonstrated in urine and diagnosis was based on the anatomopathological findings: This patient required reconstructive surgery. CONCLUSIONS: Although bilharziasis is uncommon in our setting, its incidence is rising due to increasing migration and travel. The disease has different clinical manifestations depending on its stage and therefore different diagnosis and treatment. Recognizing the disease in the early stage prevents progression to the chronic stage and the morbidity and mortality of the late stage of the disease, as well as more aggressive treatment. PMID- 11196392 TI - [Bladder metastasis of signet-ring cell adenocarcinoma from the stomach]. AB - OBJECTIVE: To describe an additional case of metastatic bladder tumor from gastric signet-ring cell adenocarcinoma. METHODS/RESULTS: Local recurrence was demonstrated by gastrointestinal endoscopy and biopsy in a 52-year-old female who underwent total gastrectomy for signet-ring cell gastric adenocarcinoma two years earlier. A CT scan showed bilateral hydronephrosis and diffuse thickening of the bladder wall. Bladder biopsy demonstrated signet-ring cell adenocarcinoma. Palliative treatment with ureteral catheterization was instituted. CONCLUSIONS: Signet-ring cell adenocarcinoma of the bladder is usually a primary tumor. Metastatic signet-ring cell adenocarcinoma to the urinary bladder is uncommon. PMID- 11196393 TI - [Basal cell carcinoma of the penis]. AB - OBJECTIVE: To report an uncommon case of basal cell carcinoma of the penis. METHODS: A case of basal cell carcinoma of the penis is presented. This has been the only case of this tumor type detected in our setting. The literature is briefly reviewed. RESULTS/CONCLUSIONS: Basal cell carcinoma of the penis is rare. To date only 20 cases have been reported in the literature. To our knowledge, no case of distant metastasis has been documented. Diagnosis by gross examination may be difficult due to the broad polymorphism of this lesion and must be confirmed by histological analysis. PMID- 11196394 TI - [Lipoma of spermatic cord; report of a case]. AB - OBJECTIVE: To report an additional case of lipoma of the spermatic cord, an uncommon, silent tumor. METHODS: A case of lipoma of the spermatic cord is described. The patient had presented with an enlarged scrotum with no symptoms. The literature on lipoma of the spermatic cord is briefly reviewed, with special reference to its diagnosis, forms of presentation and treatment. RESULTS: US evaluation demonstrated a mass adhered to the epididymis. An epididymal tumor was suspected and surgical exploration by the inguinal approach was performed. CONCLUSIONS: Lipoma is the most common tumor of the spermatic cord. Its etiology is unknown. It frequently appears in the fourth and fifth decades of life and usually involves the left hemiscrotum. It is silent and is detected by enlargement of the scrotum. The diagnosis is histological supported by US, which offers a reliability of 80%-100%. Treatment is by surgery in all cases. PMID- 11196395 TI - [Non-functional renal paraganglioma associated with carotid paraganglioma and appendicular mucocele]. AB - OBJECTIVE: A case of nonfunctional renal paraganglioma associated with appendicular mucocele and metachronic carotid paraganglioma is presented. METHODS/RESULTS: A 68-year-old patient consulted for abdominal pain. Patient evaluation with US, CT and opague enema showed an elongated mass that compromised the cecum and a solid mass in the right kidney. The patient underwent appendectomy and radical right nephrectomy. The anatomopathological findings showed an appendicular mucocele and renal paraganglioma. The postoperative hormone analyses were normal. A carotid paraganglioma was removed 8 months later. CONCLUSIONS: Renal tumors arising from neural crest cells are uncommon. To our knowledge, this is the third case of nonfunctional renal paraganglioma reported in the literature. The associated appendicular mucocele was an incidental finding. PMID- 11196396 TI - Comparison of the efficacy of fluoxetine alone vs. fluoxetine plus local lidocaine ointment in the treatment of premature ejaculation. AB - OBJECTIVE: The present study compares the efficacy and side effects of fluoxetine alone vs. fluoxetine plus local lidocaine ointment in the treatment of premature ejaculation. METHODS: Forty-three patients suffering from premature ejaculation were studied. The exclusion criteria were erectile dysfunction, loss of libido, alcohol and substance abuse, mental retardation, diabetes mellitus, thyroid disease, hypotension, previous use of these drugs and urogenital infections. The patients' ages ranged from 19 to 48 years (mean age 28 +/- 1.6). They had regular sexual lives. They had normal psychiatric consultation and the Glombock Rast Sexual Satisfactory Test (GRISS) psychiatric test were in accordance with premature ejaculation. RESULTS: The patients were assigned to two groups. Twenty six patients, aged 21 to 36 years (mean age 27), received only fluoxetine 20 mg/day (1 capsule) for a week which was later increased to 40 mg/day (2 capsules). Seventeen patients, aged 19 to 48 years (mean age 31), were given fluoxetine 20 mg/day plus local application of lidocaine ointment. The patients and partners were re-evaluated 8 weeks after the treatment. The results were classified as unsuccessful, improvement and cure. The chi-square test was used for statistical analysis. In the fluoxetine group, 8 (30.8%) patients cured, 11 (42.2%) showed improvement and there were 7 failures (26.9%). In the combination treatment group, 9 (52.9%) patients cured, improvement was observed in 5 (29.4%) and failure in 3 (17.6%). Side effects in group I were observed in 6 patients (23%) and in 5 (29.4%) in group II. There were no statistical differences between the two groups according to the side effects (p > 0.01). No patients were excluded from the study due to side effects. CONCLUSION: The combination of fluoxetine plus local application of lidocaine ointment was found to be more effective than fluoxetine alone in the treatment of premature ejaculation. However, the results should be confirmed in further studies with a placebo group to rule out the placebo effect. PMID- 11196397 TI - Associations between thoracic kyphosis, head posture, and craniofacial morphology in young adults. AB - The aim of the present study was to investigate associations between thoracic hyper- and hypokyphosis, head posture, and craniofacial morphology in young adults. Using forward bending test and spinal pantographic measurements, 31 subjects, 16 with thoracic hyper- and 15 with hypokyphosis, were selected from a population-based cohort of 430 young adults. Lateral roentgen-cephalograms were taken in natural head posture and craniofacial and postural angular measurements were calculated. Any statistically significant differences between the groups thoracic hyperkyphosis and thoracic hypokyphosis--were analysed using Student's t test. Subjects with thoracic hyperkyphosis had a larger atlantocervical angle (At/ CVT, P < 0.01) than subjects with thoracic hypokyphosis. However, head position (NSL/VER) was similar in both groups, probably owing to the visual perception control of craniovertical relation. There was no statistically significant difference in craniofacial morphologyy between the groups. PMID- 11196398 TI - Oral health behavior and attitudes of adults in Lithuania. AB - In Lithuania, the oral health system is currently in transition and systematic data are needed for public oral health care planning. The objectives of this study were (i) to describe the self-assessment of oral health status in Lithuanian adults, the oral hygiene practices, and dental visiting habits; (ii) to assess the attitudes towards teeth and oral health, dental care and oral health services; (iii) to determine whether oral health attitudes and behavior are affected by socio-economic factors; and (iv) to analyse the association between self-care practices and use of oral health services. The study comprised random samples of 35-44-year-olds (n = 381) and 65-74-year-olds (n = 302). Data were collected during 1997 98 by means of self-administered questionnaires and the response rate was 53%. Nearly all persons of ages 35-44 had natural teeth, whereas 14% of 65-74-year-olds were edentulous. Among the dentate persons, 45% of the young adults against 36% of the elderly claimed having poor teeth, and 66% and 55%, respectively, had experience of pain from teeth or mouth during the past year. At ages 35-44, 33% of participants reported toothbrushing at least twice a day and this was the case for 21% of 65-74-year-olds. Dental visits within the past year were indicated by 60% of young adults and 43% of the elderly; 83% of all participants reported that their last visit to the dentist was due to acute oral symptoms. In general, the participants had positive dental knowledge and attitudes; however, 56% were unaware of any effect of fluoride. The bivariate analyses showed that perceived oral health status and oral self-care practices were related to use of dental services. The multivariate analyses of dental visiting habits revealed the effects of gender, urbanization, presence of natural teeth, experience of dental problems, attitudes to dental care and dentists, and education. In conclusion, preventive dental services should be introduced and the establishment of community-based oral health promotion programs is urgently needed for Lithuania. PMID- 11196399 TI - Immunolocalization of interleukin-8 and proliferating cell nuclear antigen in gingival keratinocytes in patients with periodontitis. AB - The aim of this study was to investigate the relation between local expression of IL-8 and the localization of neutrophilic granulocytes, using CD16 as a marker of neutrophils. We also investigated the correlation between IL-8 and epithelial proliferation using proliferating cell nuclear antigen (PCNA) as a marker of proliferation. The distribution of IL-8, CD16 and PCNA/cyclin was determined by immunocytochemical techniques. We used cryostat-cut sections from gingival biopsies harvested from 5 subjects with and 5 subjects without periodontitis. Our histological examination demonstrated that the localization of neutrophilic granulocytes in gingival tissue from patients with periodontitis did not correlate with the expression of IL-8. In all tissue sections from patients and controls, the inflammatory cells accumulated near the pocket epithelium and only a few leukocytes deviated from this pattern. In the patient group, keratinocytes not belonging to the pocket or junctional epithelium expressed IL-8 without any evidence of a chemoattractant effect on neutrophils. The marker of proliferation, PCNA/cyclin, was expressed in keratinocytes in the basal cell layer. The expression was less pronounced in the control group. Our finding that IL-8 was expressed in proliferating cells suggests that IL-8 may have a role in keratinocyte proliferation. PMID- 11196400 TI - Avoidance of dental visits: the predictive validity of three dental anxiety scales. AB - The purpose of this study was to determine the sensitivity, specificity, positive and negative predictive values for Corah's Dental Anxiety Scale (DAS) and two modified versions of it (MDAS; MDAS/4). A questionnaire was mailed to a simple random sample of 1,190 25-year-old residents in the west of Norway in 1997. Half the sample received DAS, the other half MDAS. The response rate after one reminder was 62%. The respondents completed the scales, gave demographic particulars and answered one question about dental visiting habits during the last 5 years plus an open-ended question about reasons for non-attendance. Using the answers to the latter question as validating criterion, it was found that, for all scales, sensitivity decreased while specificity improved when changing from a liberal to a stringent cut-off point. The scales gave low positive predictive values (< or = 0.26), but high negative predictive values (> or = 0.98). Since DAS and MDAS/4 gave almost identical findings, the two samples were combined. At a cut-off point > or = 13 sensitivity was 0.83, specificity 0.84, positive predictive value 0.18 and negative predictive value 0.99. The corresponding estimates when the cut-off point was > or = 15 were 0.67, 0.90, 0.22 and 0.98. It is concluded that, in this test, DAS and the two versions of MDAS gave acceptable, or near acceptable sensitivity, specificity and negative predictive values, but far too low positive predictive values to be useful for prediction at the individual level. PMID- 11196401 TI - Trends in dental and medical research and relevance of randomized controlled trials to common activities in general dentistry. AB - The aim was to study publication trends in dental and medical research as well as the proportion of randomized controlled trials in dental research (RCT-Ds) of relevance to common activities in general dentistry. The study was based on Medline searches, 1969 99 (MeSH terms). Data from Public Dental Services (county of Ostergotland, Sweden) were used to find the most common activities in the practice of general dentistry,. In dental research the annual number of publications had decreased from 5,900 in 1969 to 4,400 in 1999, corresponding to 9,100 and 14,000, respectively, in medical research. Clinical trials in dental research had increased to 7% and RCT-Ds to 5% of all dental research during 1969 99. In medicine, clinical trials and randomized controlled trials had increased to 2% and 1%, respectively. In dental and medical research, meta-analyses (MAs) totalled 0.1-0.2% in 1994 and 1999. One out of 200 dental research publications in 1979 99 was an RCT-D of relevance to the most common activities in general dentistry. These activities contributed to more than 80% of the dental care of children and adolescents and to more than 60% of the dental care of adults in 1999. PMID- 11196402 TI - Hyposalivation and iron stores among individuals with and without active dental caries. AB - The aims of the study were to investigate frequencies of low unstimulated whole saliva (UWS) levels and low serum ferritin (S-f) levels among individuals with active dental caries (ADC) and dental caries inactive (DCI) individuals and to compare the relationship between UWS and S-f levels. In this descriptive study, 48 ADC patients and 48 DCI individuals were compared. The two groups were matched regarding age and sex (30 females and 18 males in each group, age range 15-40 years). In the ADC group, 32 individuals (67%) had low (< or = 0.20 ml/min) UWS levels compared with 13 individuals (27%) in the DCI group. This difference was statistically significant (P < 0.001). The mean values of UWS were significantly lower in the ADC group compared to the DCI group (mean ml/min +/- SD) 0.20 +/- 0.13 and 0.33 +/- 0.24, respectively (P = 0.002). There were significant differences for females but not for males when comparing frequencies of low UWS levels (P < 0.001) and mean UWS levels (P = 0.002). There was no difference in S f levels between the two groups. Neither was any correlation between UWS and S-f found. In conclusion, the significant negative relationship found between UWS and ADC indicates that a suppressed defense for dental caries activity could play a more important role in ADC than previously presumed, especially among females. The absence of a correlation between UWS and S-f might indicate that saliva secretion will not be stimulated by iron supplementation. PMID- 11196403 TI - Changes in TMD signs and in mandibular movements from 10 to 15 years of age in relation to articulatory speech disorders. AB - This study is part of a longitudinal study on the associations between different orofacial dysfunctions. The aim was to determine changes in signs of temporomandibular disorders (TMD) and in mandibular movement capacity in subjects with articulatory speech disorders and in controls by re-examining a sample of 187 previously studied children from 10 to 15 years of age. Articulatory speech disorders were diagnosed by a phoniatrician. Mandibular movement capacity, signs of TMD, occlusal contacts/ interference and slide between retruded and intercuspal positions were recorded by a dentist. The follow-up results showed that mandibular mobility mainly increased up to the age of 15, but there was a decrease in protrusion capacity in almost half of the cases. This fluctuation probably reflects the normal changes in growth pattern. Signs of TMDs proved to be inconsistent in nature, especially among the controls. With age, girls in the control group, more so than boys, were prone to new signs of TMD, but no gender difference was found in the group of subjects with misarticulations of speech. The findings indicate that in adolescence different orofacial dysfunctions are related. PMID- 11196404 TI - Sealants and xylitol chewing gum are equal in caries prevention. AB - Sealants and xylitol have been demonstrated to prevent dental decay, but their effect has never been compared in the same study. Regular use of xylitol chewing gum during 2 or 3 school years was compared with application of occlusal sealants in a randomized study. The reliability of the clinical observations was controlled by examining the presence of dental decay in the same teeth from bitewing radiographs in a blind study. After 5 years, no statistically significant differences between the sealant and xylitol groups were found. The results were in line with the results from separate studies with sealants or xylitol. There were no great differences between the costs of the measures. The selection between the compared preventive measures has to be made on the basis of practical aspects such as caries occurrence, availability of personnel and other resources, opportunity costs, cooperation with schools, and other local conditions. PMID- 11196405 TI - Efficacy of a slow-release device containing fluoride, xylitol and sorbitol in preventing infant caries. AB - A novel slow-release administration device, the "Fall-Asleep Pacifier" (FAP), was studied as a prophylactic measure against mutans streptococcal oral infection and dental caries in a risk group of 1-year-old children by comparing the test (T, n = 34) and control (C, n = 88) groups in a prospective cohort study. In the T group the children received their fluoride tablets (Fludent, containing NaF corresp. 0.25 mg F0- , xylitol 159 mg and sorbitol 153 mg) in the evenings in FAP. In the C group the children received the same dose of Fludent crushed in food in the evenings. The proportion of children, whose plaque samples from the upper incisors were mutans streptococcus positive at the age of 24 months, was significantly (P < 0.05) greater in group C (25%) than in group T (9%). The children in the T group developed significantly (P < 0.001) less (none) new dentinal carious lesions in their primary dentitions than the children in the C group between 2 and 3 1/2 years of age. Fifty-four percent of the children to whom the FAP was offered complied with regular use of it. The beneficial effect observed in the T group compared with the C group was apparently mostly due to the administration mode via FAP, which could prolong the intra-oral bioavailability of the prophylactic preparation. PMID- 11196406 TI - The outcomes of mandibular third molar removal and non-removal: a study of patients' preferences using a multi-attribute method. AB - The aim was to study patients' preferences about outcomes of mandibular third molar removal and non-removal using multi-attribute utility (MAU) methodology. The study comprised three stages. Stage 1: Elicitation of domains, i.e. main areas of patients' lives which could be affected by third molar removal and non removal. Stage 2a: Interdomain weighting was obtained by relative weighting of the domains elicited in Stage 1. Stage 2b: Intradomain weighting obtained by patients' designation of values for different health states of each domain. Stage 3: Rating of outcomes. The patients were asked to imagine experiencing a variety of outcomes of mandibular third molar removal and non-removal, described in 19 short vignettes. The numbers of patients interviewed for the three stages were 30, 78, and 55, respectively. Five domains were identified. The mean relative weightings were approximately equal for the domains "Home and social life" and "General health and well-being", followed in order of importance by 'Job and studies" and "Health and comfort of mouth, teeth and gums". "Your appearance" received the lowest mean relative weighting. The vignette, which described the presence of a fluid-filled sac and suggested that this tooth must be removed, received the highest mean preference (least effect on patients' lives). The lowest mean preference (most effect on patients' lives) was generated by the vignette, which stated that the jaw was broken and that the teeth must be wired together for 6 weeks. We conclude that, from the patient's perspective, outcomes of non-removal were preferable to outcomes of mandibular third molar removal. PMID- 11196407 TI - Growth hormone and cortisol in serum and saliva. AB - Salivary diagnosis is a developing area in clinical chemistry and dentistry. Cortisol analyses from saliva have been used in pediatric practice and as doping tests. Growth hormone (hGH), also a stress hormone, has not been analyzed from saliva. We studied the serum and saliva of 51 healthy subjects. The samples were taken at 8:00 in the morning after 12 h fasting. Cortisol concentrations were analyzed using RIA. An immunoradiometric assay was applied for analyzing serum and salivary hGH. The validity of this method developed in our laboratory was found to be good. The results showed correlation of salivary cortisol with that of serum (r = 0.47, P < 0.001). Salivary hGH concentrations were 1000-fold lower than the respective values in serum, but a clear correlation was found between salivary and serum hGH levels (r = 0.59, P < 0.001). PMID- 11196408 TI - Steroidogenic factor 1 is a monomeric orphan, but does not work alone. PMID- 11196409 TI - The activation function of steroidogenic factor-1 is impaired in ACTH-resistant Y1 mutants. AB - This study explores the basis for the altered function of steroidogenic factor-1 (SF1) in a family of ACTH-resistant Y1 adrenal cell mutants. As determined in electrophoretic mobility shift assays, the DNA binding activity of SF1 was not impaired in the mutant clones. Instead, the ability of SF1 to interact with the coactivator, GRIP1 was affected as determined in a modified mammalian 2-hybrid assay. These findings indicate that the mutants harbor a defect affecting the activation function of SF1. PMID- 11196410 TI - Baboon cytochrome P450c11 is encoded by more than one gene. AB - Two P450c11 genes, sharing 99% homology, were cloned from Cape baboon adrenal tissue using RT-PCR. The cDNAs showed 96% and 94.6% sequence identity to human P450c11 and aldosterone synthase, respectively. One of the gene sequences contained a termination codon in exon one. The cloned cDNAs were expressed in COS 1 cells and the metabolism of deoxycorticosterone to corticosterone investigated. The expressed enzyme exhibited 1 beta hydroxylase activity, but no aldosterone synthase activity. PMID- 11196411 TI - Expression of three negative regulators of CYP17 gene transcription in adrenocortical cells. AB - The expression of negative regulators of CYP17 gene expression: DAX-1, COUP-TF and N-CoR was investigated in bovine adrenocortical cells in primary culture. The cells were incubated for 6 hours in a defined medium, containing ACTH (10 nM) or forskolin (25 microM). Total RNA was isolated, the concentration of CYP17 gene transcript was determined by hybridization analysis, and polyA RNA was reverse transcribed to obtain cDNA. Fragments of CYP17, DAX-1, COUP-TF, N-CoR and beta actin cDNA were amplified by PCR and the amplified cDNAs were analyzed by agarose gel electrophoresis followed by densitometry. It was found that DAX-1 and COUP-TF mRNA levels were unaffected by treatment with ACTH or forskolin. On the contrary, both compounds enhanced the level of mRNA encoding N-CoR. Under the same conditions, ACTH or forskolin substantially stimulated CYP 17 mRNA accumulation. Our results suggest that in the adrenocortical cells in culture, the expression of DAX1 and COUP-TF is constitutive, whereas N-CoR expression might be inducible. PMID- 11196412 TI - Regulation of CYP11B2 gene expression by protein kinase C. AB - Bisindolylmaleimide, a protein kinase C (PKC) inhibitor, was shown to stimulate the hamster CYP11B2 promoter activity in transfected NCI-H295 cells. In this study we have found that TPA, an activator of PKC, also inhibited the hamster CYP11B2 promoter activity. DAG-dependent PKC alpha and PKC epsilon, and atypical PKC zeta were detected in hamster adrenal zona glomerulosa, whereas the isoforms alpha, epsilon, zeta and theta were found in NCI-H295 cells. CYP11B2 promoter activity was inhibited in cells co-transfected with constitutively active PKC alpha and epsilon mutants, whereas it was increased with the constitutively active PKC zeta mutant. Dominant negative PKC alpha, epsilon and zeta mutants stimulated the promoter activity. Go6976, a specific inhibitor of classical PKCs, enhanced promoter activity, providing further evidence that PKC alpha, the only classical PKC revealed in hamster adrenal and NCI-H295 cells, was involved in the promoter inhibition. PMID- 11196413 TI - Transcriptional regulation of steroid receptor coactivator-1 (SRC-1) in glucocorticoid action. AB - Diverse mechanisms of steroid receptor action have been clarified in recent years, as a consequence of the discovery of multiple coactivators. Among them, steroid receptor coactivator-1 (SRC-1) is a member of the p160 coactivator families, which are 160 kDa proteins that interact with steroid receptors in a hormone-sensitive manner. Since coactivators function as transcriptional power boosters, subtle changes in coactivator expression levels in certain cells markedly change of receptor-mediated transcriptional activity. Expression of the glucocorticoid receptor (GR) has been shown to be autoregulated in glucocorticoid action, i.e., GR is downregulated by its cognate ligand, indicating that this autoregulation of GR may protect target cells against excessive hormone action. In the present study, we examined whether coactivator expression levels are also regulated by glucocorticoids. Among several coactivators, the SRC-1 mRNA level was downregulated by dexamethasone treatment in rat tissues, such as liver, heart, kidney, stomach, and cerebrum, in vivo. We also demonstrated dexamethasone mediated downregulation of SRC-1 mRNA and its protein levels in rat renal mesangial cells in vitro. These results suggest that ligand-mediated downregulation of SRC-1 is crucial in the physiology of glucocorticoid action. PMID- 11196415 TI - Transcriptional regulation of the gene encoding the StAR protein in the human adrenocortical cell line, H295R by cAMP and TGFbeta1. AB - In the present work, we have analyzed the transcriptional regulation of StAR expression in the human adrenocortical cell line H295R. We observed that StAR mRNA levels rapidly increased in response to forskolin, starting after 2 h of treatment and reaching a maximum by 12 h. Deletion analysis of the human StAR promoter demonstrated that the first 150 bp upstream of the transcription start were sufficient for both basal and cAMP-induced expression of a reporter gene. We demonstrate that out of the three binding sequences for the steroidogenic factor 1 (SF-1) only the central one (-105 to -96) is implicated in both basal and cAMP induced StAR expression. In addition, another important regulatory element for both basal and cAMP-induced StAR expression is present between -62 and -24 upstream of the transcription start. We also show that TGF1beta1 inhibits StAR expression at the transcriptional level. We found that the TGFbeta-inhibitory element lies between -150 and -85 upstream of the transcription start and that the SF-1 binding sites are not implicated in TGFbeta1 regulation. PMID- 11196414 TI - Orphan receptors COUP-TF and DAX-1 as targets in disordered CYP17 expression in adrenocortical tumors. AB - CYP17 gene transcription is activated by SF-1 binding to a cyclic AMP-responsive sequence within the promoter region of the gene, and its transcription is inhibited by COUP-TF binding to the sequence. Another orphan receptor, DAX-1, is shown to act as a suppressor of SF-1-mediated transcription. We examined the expression level of these orphan receptors in adrenocortical tumors and compared the results with CYP17 expression. CYP17 was highly expressed in cortisol producing adenomas, whereas COUP-TF and DAX-1 expression levels were very low. In deoxycorticosterone-producing adenomas, on the other hand, CYP17 expression was extremely low, whereas DAX-1 was highly expressed and SF-1 expression was slightly decreased. In conclusion, the reciprocal expression of CYP17 and the transcriptional repressors COUP-TF and DAX-1 indicates that these orphan receptors have a pathophysiologic role in the excessive hormone production in cortisol- and deoxycorticosterone-producing adrenocortical tumors. PMID- 11196416 TI - Pituitary-adrenal axis regulation in CRH-deficient mice. AB - Corticotropin-releasing hormone (CRH)-deficient (knockout (KO)) mice demonstrate severely impaired adrenal responses to restraint, ether, and fasting, and lack the normal diurnal glucocorticoid (GC) rhythm. Here, we summarize recent studies determining the role of CRH in augmenting plasma adrenocorticotrophic hormone (ACTH) concentration after glucocorticoid withdrawal and pituitary-adrenal axis stimulation in the context of inflammation. Even though GC insufficient, basal pituitary proopiomelanocortin (POMC) mRNA, ACTH peptide content within the pituitary, and plasma ACTH concentrations are not elevated in CRH KO mice. POMC mRNA content in CRH KO mice increases following adrenalectomy, and this increase is reversed by GC, but not aldosterone, replacement. In marked contrast to the increase in POMC mRNA, plasma ACTH does not increase in the CRH KO mice following adrenalectomy. Administration of CRH to adrenalectomized CRH KO mice results in acute, robust ACTH secretion. Thus, loss of GC feedback can increase POMC gene expression in the pituitary, but CRH action is essential for increased secretion of ACTH into the circulation. While GC secretion is impaired in CRH KO mice after most stimuli, we have found near-normal GC responses to inflammation and systemic immune challenge. Studies in mice with CRH and IL-6 deficiency reveal that IL-6 is essential for activation of the pituitary-adrenal axis during inflammatory and other stressors in the absence of CRH. PMID- 11196418 TI - Requirement of WT1 for gonad and adrenal development: insights from transgenic animals. AB - Development of the gonad and adrenal gland occurs in close proximity and it has been proposed that they share a common primordium. Recent knockout and transgenic studies in mice have demonstrated that besides the orphan nuclear receptor SF1, the Wilms' tumor suppressor gene WT1 is important for gonad and adrenal gland development. WT1 is a complex gene with at least 24 isoforms produced from its locus. Although the role of each isoform is not yet understood, biochemical studies and analyses of human patients suggest that they do serve different functions in the cell. Here we present our current view of the part WT1 may play in the development of the gonad and discuss its possible role in the formation of the adrenal primordium. PMID- 11196417 TI - Approaches to define the role of SF-1 at different levels of the hypothalamic pituitary-steroidogenic organ axis. AB - Targeted gene disruption has produced knockout mice globally deficient in the orphan nuclear receptor steroidogenic factor 1 (SF-1). These SF-1 knockout mice lacked adrenal glands and gonads and consequently exhibited adrenocortical insufficiency and sex reversal of their internal and external genitalia. They also had impaired expression of gonadtropins in the anterior pituitary gonadotropes and agenesis of the ventromedial hypothalamic nucleus (VMH), confirming roles of SF-1 at all three levels of the hypothalamic-pituitary steroidogenic organ axis. Ongoing experiments are directed at using evolving techniques for tissue-specific gene inactivation to define the roles of SF-1 within discrete sites of the hypthalamic-pituitary-steroidogenic organ axis. PMID- 11196419 TI - Fetal hypothalamic-pituitary adrenal (HPA) development and activation as a determinant of the timing of birth, and of postnatal disease. AB - Birth in most animal species is triggered by the fetus through activation of the fetal hypothalamic-pituitary-adrenal (HPA) axis. Preterm birth, may be associated with precocious activation of fetal HPA function, reflecting the fetal response to an adverse intrauterine environment. There is a progressive and concurrent increase of ACTH1-39 and cortisol (F) in the circulation of fetal sheep during the last 15-20 days of pregnancy (term, day 145-150) associated with increased expression of hypothalamic CRH pituitary POMC and adrenal ACTH receptor and steroidogenic enzymes, particularly P450 C17. Similar changes occur with fetal hypoxemia. Negative feedback is ameliorated by decreased pituitary and hypothalamic glucocorticoid receptor, increased CBG, and altered fetal pituitary 11B-hydroxysteroid dehydrogenase type 1. Repeated fetal hypoxemia, diminishes the fetal-pituitary ACTH response, but increases fetal adrenal responsiveness. Fetuses exposed to maternal glucocorticoid in late gestation are growth restricted with altered postnatal HPA responsiveness and glycemic responses that reproduce the insulin resistance of type 2 diabetes. We conclude that the level of fetal HPA activity is crucial not only for determining gestation length, but also predicts pathophysiologic adjustment in later life. PMID- 11196420 TI - DHEA replacement in women with adrenal insufficiency--pharmacokinetics, bioconversion and clinical effects on well-being, sexuality and cognition. AB - Standard replacement for adrenal insufficiency (AI) consists of glucocorticoids and mineralocorticoids while DHEA deficiency is routinely ignored. Thus, AI represents the ideal pathophysiological model of isolated DHEA deficiency. We investigated the effects of DHEA replacement in 24 women with primary and secondary AI employing a double blind, placebo-controlled, randomized crossover design. A DHEA dose of 50 mg/d was chosen based on preceding single-dose pharmacokinetics and bioconversion studies. Each patient received four months of treatment with DHEA and four months placebo, with a one-month washout period. Measurements included serum steroid hormones, somatotropic parameters and psychometric assessment of well-being, mood, cognition and sexuality. Treatment with DHEA raised the initially low serum concentrations of DHEA, DHEAS, androstenedione, and testosterone into the normal range. DHEA induced a slight increase in serum IGF-I, but only in patients with primary AI, suggesting a growth hormone-mediated effect. DHEA treatment significantly improved overall wellbeing as well as scores for depression, anxiety, and their physical correlates. Furthermore, DHEA significantly increased both sexual interest and the level of satisfaction with sex. DHEA replacement had no influence on the cognitive performance, which was already on a high level at baseline. In conclusion, DHEA replacement improves well-being and sexuality in women with adrenal insufficiency. If this is due to a direct effect of DHEA on the brain, an indirect effect via increased androgen synthesis, or both, remains to be elucidated. Long-term studies in patients of both sexes are needed to further define the role of DHEA in standard replacement for adrenal insufficiency. PMID- 11196421 TI - The HPA axis and the stress response. PMID- 11196422 TI - Gene dosage effects of steroidogenic factor 1 (SF-1) in adrenal development and the stress. PMID- 11196423 TI - The localization of DHEA sulfotransferase in steroidogenic and steroid metabolizing tissues of the adult rhesus macaque monkey. AB - Dehydroepiandrosterone sulfate is a major secretory product of the human adrenal cortex during intrauterine development as well as during adulthood. There are few animal experimental models that share this characteristic pattern of adrenal cortical steroidogenesis, which probably accounts for the relative paucity of information about the control of development and function of the adrenal androgen secretory apparatus. Adrenal androgen production in the rhesus macaque shares many similarities with that of the human. We sought to determine the tissue distribution of the enzyme DHEA sulfotransferase (DST) in the rhesus. Tissues were harvested at the time of autopsy from 7 adult monkeys (5 M, 2 F) ranging from 8-15 yrs old, and were fixed in 4% paraformaldehyde, embedded in paraffin, and sectioned at 5 mu thickness. Tissue sections were immunostained for DST with an anti-human liver DST antibody. DST was not detected in the testis or ovary. In the liver, immunoreactive DST was detected only in hepatocytes and in the kidney, DST was found only in the epithelial cells lining the collecting tubules. In the adrenal, DST was present in the cells of the zona reticularis but was not found in the cells of the medulla, zona fasciculata or in the very prominent zona glomerulosa. DST was most prominent in cells that were closest to the reticularis medullary border. In most adrenals evaluated, the immunopositive cells were scattered, rather than forming a continuous band of cells around the medulla. The tissue distribution of DST in the adult rhesus macaque is qualitatively similar that observed in the adult human. These data aresuggestive that the rhesus might be an excellent model for the exploration of factors that regulate adrenal androgen production during development, aging, and in response to illness and stress, all of which have been found to be associated with variations in DHEA and DHEA sulfate production in the human. PMID- 11196424 TI - N-proopiomelanocortin (1-77) suppresses expression of steroidogenic acute regulatory protein (StAR) mRNA in the adrenal gland of the fetal sheep. AB - In the sheep, there is a rapid increase in fetal adrenal growth and steroidogenesis during the last 10-15 days gestation. Recently, we have shown that infusion of POMC (1-77) increases fetal adrenal growth and expression of CYP17 mRNA but does not significantly alter fetal plasma cortisol concentrations [1]. We therefore investigated the effects of infusion of bovine POMC (1-77) and its biosynthetic derivative POMC (1-49) on adrenal StAR mRNA expression. At 136d gestation, POMC (1-77) (n=5 fetuses; 2microg/ml/h), POMC (1-49) (n=5 fetuses, 2microg/ml/h) or Saline (n=5 fetuses, 1ml/h) was infused for 48h. At 138d, fetal adrenal glands were collected and frozen in liquid N2 until RNA was extracted. Northern blot analyses demonstrated a major transcript for StAR mRNA at 3.0kb in fetal adrenal glands from all treatments. The membrane was stripped and re-probed with a P-labelled rat 18S rRNA oligo-probe to verify equal RNA loading. Infusion of POMC (1-77), but not POMC (1-49), resulted in a suppression of fetal adrenal StAR mRNA:18S rRNA when compared to adrenal StAR mRNA:18S rRNA from saline infused controls. Our data suggest POMC (1-77) may act via separate mechanisms to increase fetal adrenal growth and to limit adrenal steroidogenesis through suppression of StAR mRNA. PMID- 11196425 TI - Corticosteroid production by fetal rat hippocampal neurons. AB - 11beta-hydroxylase and aldosterone synthase catalyse the final stages of corticosterone and aldosterone synthesis respectively. Previously, we established that they are expressed in the rat brain, particularly the cerebellum and the hippocampus. Primary cultures of fetal rat neurons were studied. RT-PCR and immunohistochemistry established that neurons express 11beta-hydroxylase and aldosterone synthase mRNAs and protein. After incubating the cells with 10microM DOC for 24 hours, medium was analysed for aldosterone and corticosterone. Median % conversion of DOC to corticosterone was 7.6% compared to 0.4% in controls. Median % conversion of DOC to aldosterone was 6.2% compared to 0.06% in controls. Corticosteroids mediate a number of functions of mammalian brain, including blood pressure homeostasis, salt appetite and neuronal excitability. Local production of these steroids could have significant effects on these processes. PMID- 11196426 TI - Chronic stress effects on the rat adrenal cortex. AB - Under the influence of a chronic permanent stress, the adrenal function as well as the entire hypothalamic-pituitary-adrenal axis (HPAA) suffered an adaptation process that resulted in the normalization of the studied stress hormones (ACTH, corticosterone and aldosterone) with the exception of plasma renin activity which first diminished and at the end increased. ACTH receptors exhibited a dual response since after 14 days of permanent stress MC2-R showed a slight reduction while MC5-R was still up-regulated. PMID- 11196427 TI - Functional expression of the human ACTH receptor gene. AB - The ACTH receptor is the type 2 (MC2R) among the melanocortin receptor family and is expressed almost exclusively in the adrenal cortex. The human MC2R (hMC2R) was very difficult to express in heterologous cell lines. We have succeeded in transient and stable expression of hMC2R using the M3 melanoma cells. Moreover, we have found that the expressed hMC2R in M3 cells showed similar ACTH binding affinity and coupling to adenylate cyclase as the MC2R of normal human adrenal cells, contrarily to most of the other expression cell models. In these conditions, we have been able to test several mutant hMC2R described in patients with the familial glucocorticoid deficiency syndrome (FGD) using this cell line. PMID- 11196428 TI - Activation and phosphorylation of angiotensin AT1 and AT2 receptors. PMID- 11196429 TI - Hypophysectomy results in a loss of connexin gap junction protein from the adrenal cortex. AB - To test the hypothesis that gap junctions are dependent on the tropic state of the adrenal gland, the effect of hypophysectomy on connexin 43 (alpha1-Cx43) gap junction protein occurrence and distribution was examined in mice. Gap junction protein occurrence was assessed with immunohistochemical techniques. In the adrenal gland from intact animals, alpha1-Cx43 gap junction protein was detected in the zonae fasciculata(ZF) and reticularis (ZR) while only a few alpha1-Cx43 gap junction plaques were found connecting zona glomerulosa(ZG) cells. Hypophysectomy led to a profound atrophy of the cortex which was more marked in the inner zones (zonae fasciculata and reticularis) than in the zona glomerulosa. There was a time dependent loss of alpha1-Cx43 gap junction protein in the adrenal cortex after hypophysectomy. At 33 day following hypophysectomy there was a two fold decrease in gap junctions in the zona fasciculata while the average gap junction plaque size was not different than the size seen in control animal adrenal glands.. ACTH (1U/gm body weight) treatment in hypophysectomized animals increased the number of gap junction plaques in the zona fasciculata. Hypophysectomy led to diminished alpha1-Cx43 gap junction expression in the zona fasciculata which could be restored by ACTH treatment. Because altering the tropic state of the adrenal glands via hypophysectomy leads to a reduction in gap junction number, it can be suggested that control of gap junction expression in the adrenal gland is hormone dependent and linked to adrenal gland function. PMID- 11196430 TI - Neuroendocrine regulation by the Agouti/Agrp-melanocortin system. PMID- 11196431 TI - Isolation of a full length ovine angiotensin II type-1 receptor (AT1-R) cDNA. AB - A full-length ovine AT1-R cDNA (2358 bases: Genebank AF254119) was isolated from ovine adrenal cortex using 3'-RACE. While homology of the 5'-untranslated region to human sequence was low (34.2%), the beginning of both human exon 1 and human exon 5 (encoding the end of the 5'-untranslated sequence/complete protein coding region/3'-untranslated sequence) were exceptionally conserved and in context. The intervening untranslated sequence showed lower homology to human sequence, but still contained four additional ATG sequences close to corresponding "in frame" TGA Stop codons shown in human to impair AT1-R translation in vitro. The putative protein coding sequence was >99% identical to the previous reported ovine genomic sequence. The predicted amino acid sequence in turn encoded a protein with the properties of a seven alpha-helix transmembrane receptor sharing closest homology (99.1%) to the bovine receptor and lowest to the rat Type la (90.5%). The 3' untranslated region showed relatively high homology to the porcine and bovine receptor cDNA, but did not share the additional 643 bases found only in the bovine 3'-untranslated region. The ovine 3'-sequence included a polyadenylation signal as well as three AUUUA destabilization sequences observed in most other species including human. Thus ovine AT1-R mRNA stability may be short lived, and control of degradation may be an additional mechanism for regulation of ovine AT1 R expression. PMID- 11196432 TI - A role for the p42/44 isoforms of MAPK in the regulation of steroid secretion from Y1 mouse adrenocortical cells. PMID- 11196433 TI - Effect of serotonin4 (5-HT4) receptor agonists on aldosterone secretion in idiopathic hyperaldosteronism. AB - Serotonin (5-HT) stimulates aldosterone secretion in man through 5-HT4 receptors positively coupled to adenylyl cyclase. In particular, it has been shown that oral administration of a single dose of the 5-HT4 receptor agonist cisapride induces a significant increase in plasma aldosterone levels (PAL) in healthy volunteers. Idiopathic hyperaldosteronism (IH) is a rare disorder characterized by hypertension, hypokalemia and bilateral adrenal hypersecretion of aldosterone. In patients with IH, administration of the 5-HT precursor 5-hydroxytryptophan (5 HTP) is followed by a significant increase in PAL. 5-HTP-induced aldosterone secretion has been attributed to the activation of central serotonergic pathways. The aim of the present study was to evaluate the effect of the oral administration of a single dose of cisapride (10 mg) on aldosterone secretion in 15 patients with IH, in a simple blind fashion versus placebo. Cisapride induced a significant increase in PAL but did not affect renin, cortisol and potassium levels. The present study demonstrates that 5-HT4 receptor agonists are able to stimulate aldosterone secretion in patients with IH. These data also indicate that hyperplastic glomerulosa tissue, like normal glomerulosa cells, expresses a functional 5-HT4 receptor. Therefore, 5-HT4 receptor antagonists may represent a new approach in the treatment of primary hyperaldosteronism. PMID- 11196434 TI - Induction of nitric oxide synthase activity in adrenal cells. AB - The induction of nitric oxide synthase (NOS) II by bacterial lypopolysaccharide (LPS) was studied in a steroidogenic mouse tumor adrenal cell line (Y1). Conditioned media from LPS-stimulated peritoneal macrophages induced an increase in NOS II expression as shown by western and northern blot analysis. Accordingly, in the presence of conditioned media an increase in nitrite levels was observed. In addition, steroid production was significantly decreased. In conclusion, NOS II expression could be induced in steroidogenic cells with a concomitant inhibition of steroid production. PMID- 11196435 TI - Rat glomerulosa cells express functional 5-HT7 receptors. AB - It has been previously demonstrated that serotonin (5-HT) is a potent stimulator of aldosterone secretion in amphibians and mammals. The aim of the present study was to characterize the type of serotonergic receptor involved in the action of 5 HT on rat glomerulosa cells. The effects of 10 serotonergic receptor agonists and 12 receptor antagonists on aldosterone secretion from perifused rat adrenocortical slices were investigated. Correlation analysis between the potencies of the different compounds in our model and those previously reported for transfected 5-HT receptors showed that the rat adrenal 5-HT receptor exhibits the pharmacological profile of the 5-HT7 receptor. RT-PCR amplification with specific primers for the 5-HT7 receptor confirmed the presence of 5-HT7 receptor mRNA in the adrenal cortex. Western blot analysis using antibodies against the 5 HT7 receptor revealed the occurrence of a protein with an apparent molecular mass of 66 kDa in the zona glomerulosa. In glomerulosa cells, 5-HT induced a concentration-dependent increase of cAMP formation. These data demonstrate that rat adrenal glomerulosa cells express functional 5-HT7 receptors positively coupled to adenylyl cyclase. PMID- 11196436 TI - Effects of cellular mediator agonists on cortisol and steroid acute regulatory (StAR) protein in bovine zona fasciculata (ZF) cells. AB - Primary cultures of bovine ZF cells were incubated for 1 h or 6h with the agonists 8-bromo-cyclic AMP (8-Br-cAMP) an activator of protein kinase A (PKA), the phorbol ester phorbol 12-myristate 13-acetate (PMA) a protein kinase C (PKC) activator, the Ca2+ ionophore, A23187, or the L-type Ca2+ channel agonist Bay K8644. Both cortisol secretion (determined by radioimmunoassay of cell medium) and cellular StAR protein levels (quantified by western blotting) were significantly increased at 6h, by all agonists. However, while all agonists stimulated cortisol secretion at 1h, StAR protein levels remained unchanged by these treatments. We conclude that in bovine ZF cells, StAR protein synthesis can be regulated by mechanisms involving activation of PKA, PKC and Ca2+ influx. However, a net increase in cellular StAR protein does not appear to be essential for the initiation for the first stage of acute steroidogenesis. PMID- 11196437 TI - An ACTH-activated protein tyrosine phosphatase (PTP) is modulated by PKA-mediated phosphorylation. AB - In adrenal cortex, ACTH regulation of steroidogenesis depends on PKA-dependent serine/threonine phosphorylation and also on the activity of protein tyrosine phosphatases (PTPs). In addition, ACTH increases total PTPs involving at least three soluble PTPs (50, 82 and 115 kDa). Serine/threonine phosphorylation of these enzymes themselves could be a regulatory mechanism of their activity since the increase of total PTP activity is dependent on PKA-activation. In this report we analyzed the effect of in vitro phospho-dephosphorylation processes on the activity displayed by the ACTH-activated PTP of 115 kDa. Using an in-gel PTP assay we demonstrate that dephosphorylation catalyzed by potato acid phosphatase (PAP) reduces the activity of the 115 kDa PTP present in ZF from ACTH-treated animals and PKA-mediated phosphorylation reverses this effect. PMID- 11196438 TI - Calcium signal and mitochondrial metabolism in steroid producing cells. PMID- 11196439 TI - Inhibition of protein tyrosine phosphatase activity blocks shape change & steroidogenesis in Y1 cells. AB - Y1 adrenocortical cells respond to forskolin stimulation with increases in steroid secretion and change of shape. The rapid rounding of flat, adherent cells which occurs is known to involve dephosphorylation of the focal adhesion protein, paxillin. We have investigated the effects of a tyrosine phosphatase inhibitor, calpeptin (CP) on steroidogenesis and shape change in Y1 cells. Forskolin treatment (FSK, 2 microM) caused marked rounding of Y1 cells (FSK = 76.3 +/- 1.5% cells rounded after 30 minutes, untreated = 2.9 +/- 0.7 % rounded); calpeptin pretreatment (CP; 100 ug/ml) had little effect on shape (9.6 +/- 2.4% rounded) but blocked the rounding response to FSK (32.1 +/- 2.1% rounded. Calpetin also eliminated the steroidogenic response to FSK ( FSK = 242 +/- 14% control ; FSK + CP = 113 +/- 18% control ) without affecting production of steroid from membrane permeant 22R-OH-cholesterol. The results support the view that dephosphorylation of paxillin is important in the rounding response and provide evidence for the involvement of tyrosine-phosphatase activity in cyclic AMP-stimulated steroidogenesis in Y1 cells. PMID- 11196440 TI - Evidence that StAR and MLN64 act on the outer mitochondrial membrane as molten globules. AB - StAR increases the flow of cholesterol from the outer to inner mitochondrial membrane (OMM to IMM), but its mechanism of action remains unclear. MLN64 is a 445 amino acid protein of unknown function that has four N-terminal transmembrane domains and whose C-terminal domain from 218-445 is 37% identical to StAR. N-62 StAR is as active as wild-type StAR, and N-234 MLN64 has 1/3 to 1/2 of StAR's activity. N-62 StAR lacks a mitochondrial leader and is confined to the cytoplasm, indicating that it acts on the OMM. Bacterially expressed N-62 StAR and N-218 MLN64 are active with isolated MA-10 cell mitochondria, indicating the proteins were properly folded. Far-UV CD spectroscopy, unfolding in urea, and fluorescence spectroscopy indicate that StAR undergoes a pH-dependent transition to a molten globule (retained secondary structure, partially lost tertiary structure) and stabilizes in mildly acid conditions. Far-UV CD data indicate that MLN64 undergoes a much less pronounced transition. Western blotting shows that normal human placenta has abundant N-terminally-cleaved 30 kDa MLN64. Partial proteolysis followed by mass spectrometry shows that the C-termini of StAR and MLN64 are sensitive to proteolysis, indicating looser folding. Our model of StAR action is that the protease-resistant domain unfolds slowly during normal mitochondrial entry, keeping StAR in contact with the OMM longer, increasing activity. The transition to the molten globule may be related to interaction with the OMM. These data are consistent with the recent crystallographic structure of N-216 MLN64 in which MLN64 binds cholesterol one molecule at a time, but are not consistent with the suggestion that StAR/MLN64 must reside in the intramembraneous space to transfer cholesterol form the OMM to the IMM. PMID- 11196441 TI - Roles of scavenger receptor BI and APO A-I in selective uptake of HDL cholesterol by adrenal cells. AB - Adrenal cells obtain cholesterol for steroid production via the selective uptake of cholesteryl ester (CE) from HDL particles, a process in which CE is transferred to the plasma membrane without degradation of the HDL particle. Although this process has been studied for two decades, only recently have the receptor and the HDL ligand been identified. Scavenger class B, type I, (SR-BI) is regulated by ACTH in adrenocortical cells in parallel with steroid production. Antibody to SR-BI blocks the uptake and utilization of HDL CE for steroid production in Y1-BS1 adrenal cells. The adrenal glands of SR-BI knockout mice are depleted in cholesterol providing complementary evidence that SR-BI is responsible for HDL CE accumulation in adrenal cells. SR-BI-mediated HDL CE selective uptake is a two-step process in which SR-BI first interacts with multiple sites in apoA-I with the amphipathic inverted alpha-helical repeat units of apoA-I serving as recognition motifs. This is followed by efficient CE transfer down its concentration gradient to the plasma membrane, a process requiring the extracellular domain of SR-BI. Other scavenger receptors bind HDL but do not afford the CE transfer step. Adrenal glands from apoA-I knockout mice lack CE stores, indicating that apoAI is essential for HDL selective uptake in vivo. ApoA-I knockout HDL particles bind normally to SR-BI but do not permit efficient CE transfer to the cell. These findings suggest that apoA-I has an important role in the transfer of HDL CE that goes beyond its function as a ligand for interaction with SR-BI. PMID- 11196442 TI - Regulation of arachidonic acid release in steroidogenesis: role of a new acyl-CoA thioestrase (ARTISt). AB - It has been well established that arachidonic acid (AA) and its metabolism to leukotrienes plays an obligatory role in steroid production. The release of AA is regulated by hormone stimulation and protein phosphorylation. We have cloned a cDNA of a phosphoprotein with a molecular mass of 43 kDa (p43), purified from the cytosol of stimulated adrenal glands. This protein acts as intermediary in the stimulation of steroid synthesis through AA release, and has been found to be a member of a recently described acyl-CoA thioesterase family. In view of the mandatory role of this protein in the activation of AA-mediated steroidogenesis, the term Arachidonic acid-Related Thioesterase Involved in Steroidogenesis (ARTISt), is proposed for p43. The present study describes the production of the recombinant protein by cDNA expression in Escherichia coli and its functional characterization. Recombinant acyl-CoA thioesterase was capable to release AA from the respective acyl-CoA, and this activity was affected by well-recognized inhibitors of AA release and metabolism: 4-bromophenacyl bromide (BPB) and nordihydroguariaretic acid (NDGA). In addition, the inhibition of acyl-CoA thioesterase activity by NDGA correlates with the inhibition of steroid synthesis produced by this compound in adrenal cortex cells. Moreover, the recombinant protein was phosphorylated in vitro by PKA. These results provide the first evidence linking acyl-CoA thioesterases with the regulation of steroidogenesis, and support a regulatory role for acyl-CoA thioesterases in steroidogenic tissues, suggesting an alternative pathway for AA release in signal transduction. PMID- 11196443 TI - Relationship of StAR expression to mitochondrial cholesterol transfer and metabolism. AB - Experiments in Y-1 and primary adrenal cells have established that basal StAR mRNA is sufficient for maximum cAMP-stimulated cholesterol metabolism providing that newly synthesized p37 StAR precursor is phosphorylated, transferred to the matrix and proteolytically cleaved to pp30. This form is active at the inner membrane. The majority of mitochondrial StAR redistributes, perhaps with cholesterol, to matrix vesicles but no longer facilitates intermembrane transfer even when appropriately phosphorylated. MA10 cells utilize a similar to Y01 cells mechanism, but sustain a higher rate of cholesterol metabolism at comparable StAR levels and exhibit much higher maximum rates. In Y-1 adrenal cells cholesterol metabolism is fully activated prior to increased StAR expression which then does not affect the rate. Thus factors other than StAR are at least as important in determining overall rates of cholesterol delivery. Following cAMP stimulation StAR is predominantly expressed as the 3.5kb form which arises from alternative polyadenylation following transcription of an extended exon 7. This form contains an AU-rich regulatory element at the 3'-end that potentially mediates the relatively rapid turnover of this form. The 1.6kb form is more stable and reaches a steady state at later time points. Turnover of both forms is coupled tightly to ongoing transcription and translation. In addition to enhanced transcription cAMP appears to direct enhanced turnover of the 3.5kb form. StAR participation in cholesterol metabolism functions at very low levels of mRNA and high efficiency at each step. PMID- 11196444 TI - Post-translational regulation of steroidogenic acute regulatory protein by cAMP dependent protein kinase A. AB - Adrenal steroid production is stimulated by adrenocorticotropin hormone activation of the cAMP-dependent protein kinase A (PKA) signaling pathway and subsequent induction of Steroidogenic Acute Regulatory (StAR) protein expression. Herein we have compared StAR mRNA and protein levels in 8-Br-cAMP-treated mouse adrenocortical Y1 and the derived PKA mutant Kin-8 cell lines to evaluate the PKA requirement in StAR expression. StAR mRNA was induced by 8-Br-cAMP-treatment of both Y1 and Kin-8 cells with maximal expression levels in Kin-8 cells approximately 50% of that observed in Y1 cells. StAR protein levels, as detected by Western analysis, were concomitantly increased in Y1 cells but were not detected in the Kin-8 cells. StAR mRNA colocalized with the active polysome fractions in both 8-Br-cAMP-treated Y1 and Kin-8 cells, indicating translation was not blocked in Kin-8 cells. Consistent with this data, a 2-fold increase in incorporation of [35S]methionine into StAR was also observed after 8-Br-cAMP treatment of both cell lines. Since StAR protein levels were not sufficient to detect by Western analysis, these data indicate that PKA functions at the post translational level to regulate StAR expression and we propose that phosphorylation of StAR by PKA contributes to protein stability. PMID- 11196445 TI - Probing structural and functional domains of human P450c17. AB - Human P450c17 performs at least six chemical transformations, but this spectrum of activity is differentially regulated by structural changes and by redox partner proteins. Furthermore, P450c17 isoforms from different species with approximately 90% amino acid identity exhibit markedly different relative rates for these transformations. Although this phenomenology has been recognized for nearly 20 years, the underlying chemistry and structural basis for these effects are poorly understood. We have constructed a structural model of human P450c17 using computational chemistry to understand informative, naturally occurring human mutations and to provide a rational basis for designing alterations in P450c17 that probe functional domains of the protein. We have mapped with considerable confidence key residues involved in the interaction with redox partner proteins, including K89, R347, and R358, which form positive charges on the "proximal" surface of P450c17. Neutralization of these charges selectively impairs 17, 20-lyase activity without large reductions in 17alpha-hydroxylase activity or 17alpha-hydroxypregnenolone binding. We are now directing our efforts to the identification of key residues in the active site that mediate the substrate specificity and catalytic selectivity of human P450c17. PMID- 11196446 TI - Role of arachidonic acid metabolism in ACTH-stimulated cortisol secretion by bovine adrenocortical cells. AB - We have studied the effects of inhibitors of arachidonic acid (AA) metabolism, nordihydroguaiaretic acid (NDGA), a lipoxygenase (LPX) inhibitor, and indomethacin (INDO), a cyclooxygenase (COX) inhibitor, on cortisol secretion and StAR protein in primary cultures of bovine adrenal zona fasciculata (ZF) cells. NDGA inhibited cortisol secretion in response to both 10(-12) M and 10(-8) M ACTH. AA (10(-4) M) partially reversed the inhibition of cortisol secretion by NDGA at 10(-12) M ACTH but not at 10(-8) M ACTH. On the other hand, INDO potentiated the cortisol response to 10(-12) M ACTH. Neither NDGA nor INDO significantly affected StAR protein levels. These results suggest a StAR protein independent role for the LPX and COX pathways in acute cortisol secretion, and support the hypothesis that LPX products of AA metabolism are key cellular signals when bovine ZF cells are acutely stimulated by physiological concentrations of ACTH (10(-12) M). PMID- 11196447 TI - The role of 11 beta-hydroxysteroid dehydrogenase in central obesity and osteoporosis. AB - Both central obesity and osteoporosis are common findings in states of glucocorticoid excess. In many tissues, including adipose tissue, hydroxysteroid dehydrogenase type 1 (11beta-HSD1) catalyses the inter-conversion of active glucocorticoid, cortisol (F) and inactive cortisone (E) and regulates exposure to the glucocorticoid receptor. As such, factors which regulate 11beta-HSD1 are likely to have an important role in adipose tissue and bone physiology. Using primary cultures of human adipose stromal cells we have investigated the effect of various factors present within the adipocyte microenvironment for their effects on 11beta-HSD1 expression. IGF-1 caused a dose dependant inhibition of 11beta-HSD1 activity in both subcutaneous and omental stromal cells. Additionally, TNFalpha treatment increased 11beta-HSD1 reductase activity and mRNA expression. In adult human bone, 11beta-HSD1, but not 11beta-HSD2, expression was demonstrated using enzyme activity studies, RT-PCR and immunohistochemistry. In contrast to liver and adipose tissues, where reductase activity predominates, both reductase and dehydrogenase activities of 11beta-HSD1 were evident in bone chips and primary cultures of human osteoblasts. The action of growth factors and cytokines on glucocorticoid sensitive tissues such as adipose tissue and bone may be mediated by modulation of local glucocorticoid metabolism at a pre-receptor level. PMID- 11196448 TI - Molecular modeling of the hamster adrenal P450C17. AB - The cytochrome P450C17 (C17) is the steroidogenic enzyme responsible for the conversion of pregnenolone and progesterone to dehydroepiandrosterone (DHEA) and delta4-androstenedione (AD) respectively. This conversion is achieved by two enzymatic activities, 17alpha-hydroxylase and 17,20-lyase, located at the same active site. In man, the adrenal C17 basically only produces DHEA. We have shown that the hamster adrenal C17 produces DHEA as well as AD. Moreover, the hamster like man produces cortisol as its major glucocorticoid. We can thus compare the hamster and human adrenal C17, and use their differences in order to elaborate a strategy for structure-function studies. We have thus engineered hamster adrenal C17 mutants which possess modified enzymatic activities. We also proceeded to elaborate a three-dimensional model of the hamster C17 to visualise the structural impact of these mutations. This model demonstrates that the mutations created are not localised at the active site, but rather in surrounding regions. These could affect the conformation of the active site, in turn, modulating the 17alpha-hydroxylase and 17,20-lyase activities. For example, the mutation T202N is located next to Val 482 and Val 483 which compose the roof of the active site. This mutation decreased both 17alpha-hydroxylase and 17,20-lyase activities, indicating the importance of the roof of the active site for general functionality of the C17. PMID- 11196449 TI - Inhibition of cytochrome P450c11 by biogenic amines and an aziridine precursor, 2 (4-acetoxyphenyl)-2-chloro-N-methyl-ethylammonium chloride. AB - The interaction of several biogenic amines and Compound A (2-(4-acetoxyphenyl)-2 chloro- N-methyl-ethylammonium chloride), an analogue of the active substance in a HPLC fraction isolated from the shrub, Salsola tuberculatiformis Botsch., with cytochrome P450c11 was investigated. Noradrenaline, octopamine and Compound A inhibited the type I DOC induced difference spectrum of P450c11 and elicited a type II difference spectrum when added alone. The Ks-values for noradrenaline, octopamine, and Compound A were 0.8 mM, 0.16 mM and 0.36 mM, respectively. Dopamine, adrenaline and synephrine did not interact with, or inhibit, P450c11. Further investigation of Compound A indicated that it is a mixed inhibitor of sheep P450c11 with a stronger competitive (Kic = 106-110 microM) than uncompetitive (Kiu = 667-737 microM) element, and that it inhibits the conversion of deoxycorticosterone to corticosterone by human 11beta-hydroxylase and aldosterone synthase with EC50 values of 97 microM and 190 microM, respectively, in fetal calf serum. PMID- 11196450 TI - Properties of an adrenal medullary protein immunorelated to steroid acute regulatory (StAR) protein. AB - Immunohistochemistry using a StAR peptide antiserum had previously revealed strong staining in rat and bovine adrenal medulla, suggesting the presence of a protein immunogenically related to StAR. Western blots of bovine medulla tissue homogenates showed the principal adrenal medullary immuno-reactive species to have a higher molecular weight (50 kDa) compared to StAR protein (30 kDa). Subcellular fractionation localised the 50 kDa species principally to the medulla cytosol. StAR peptide antiserum binding to both the 30 kDa and 50 kDa species could be specifically competed by the peptide antigen. These data suggest that the adrenal medullary immuno-reactive species and StAR protein are distinct entities, which share some features in common. PMID- 11196451 TI - Triple A syndrome--clinical aspects and molecular genetics. AB - The triple A syndrome or Allgrove syndrome (MIM*231550) is characterized by adrenocorticotropic hormone (ACTH) resistant Adrenal insufficiency, Achalasia of the cardia and Alacrima. In addition to the main features, patients frequently suffer from neurological disturbances. Dermatological abnormalities such as palmoplantar hyperkeratosis as well as other signs like short stature, microcephaly and osteoporosis point to the multisystemic character of the disorder. The molecular defect of the autosomal recessively inherited triple A syndrome is not known. We initially performed a systematic genome linkage scan in eight triple A families and were able to map the syndrome to a 6 cM interval on human chromosome 12q13 near the type II keratin gene cluster. A refinement of the triple A critical region was achieved by detailed haplotype analysis in a further 37 families from different ethnic backgrounds. There was no indication of genetic heterogeneity. The achalasia-alacrima (AA) syndrome which has been defined as a distinct clinical entity (MIM 200440) is most likely a variant of the triple A syndrome as shown by haplotype analysis in three AA families. We constructed a high-resolution BAC/PAC-based transcript map of the region which will greatly facilitate the identification of the triple A syndrome gene. The considerable intra- and interfamilial variability of the severity of the disorder implies a variable expression of an impaired pleiotropically acting gene. PMID- 11196452 TI - A new insight into the molecular basis of 3beta-hydroxysteroid dehydrogenase deficiency. AB - Classical 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase (3beta-HSD) deficiency is a rare form of congenital adrenal hyperplasia that impairs steroidogenesis in both the adrenals and gonads resulting from mutations in the HSD3B2 gene, causing varying degrees of salt-loss in both sexes and incomplete masculinization of the external genitalia in genetic males. To date a total of 34 mutations (including 5 frameshift, 4 nonsense, 1 in-frame deletion, 1 splicing and 23 missense mutations) have been identified in the HSD3B2 gene. Results from functional charaterization studies of the mutant proteins agrees with the prediction that no functional type II 3beta-HSD isoenzyme is expressed in the adrenals and gonads of the patients with the severe salt-losing form, whereas the nonsalt-losing form causes an incomplete loss in enzymatic activity, thereby leaving sufficient enzymatic activity to prevent salt loss. Recent studies have highlighted the fact that various mutations appear to have a drastic effect upon the stability of the protein, therefore providing molecular evidence of a new mechanism involved in classical 3beta-HSD deficiency. Finally, the functional characterization of the missense mutations known to be involved in this autosomal recessive disorder provides valuable information concerning the structure function relationships of the 3beta-HSD enzyme superfamily. PMID- 11196453 TI - Genotype-phenotype correlations of mutations and polymorphisms in HSD11B2, the gene encoding the kidney isozyme of 11beta-hydroxysteroid dehydrogenase. AB - Mutations in the HSD11B2 gene encoding the kidney (11-HSD2) isozyme of 11beta hydroxysteroid dehydrogenase cause the syndrome of apparent mineralocorticoid excess, a form of salt-sensitive hypertension. Enzymatic activities of mutant enzymes measured in cultured cells are correlated with several parameters of clinical severity including urinary steroid product:precursor ratios, age at diagnosis, birth weight and potassium levels, but not with blood pressure. In normals or in subjects with essential hypertension, sensitivity of blood pressure to salt loading is correlated with activity of renal 11-HSD2, as measured by an increase in the ratio of urinary free cortisol/urinary free cortisone (UFF/UFE), and also correlated with length of a CA repeat polymorphism in the first intron of HSD11B2. A functional explanation for these associations remains to be elucidated. PMID- 11196454 TI - New molecular genetic defects causing 11beta-hydroxylase deficiency (CAH). PMID- 11196455 TI - Cortisol producing adrenal adenoma--a new manifestation of Gardner's syndrome. AB - INTRODUCTION: Familial adenomatous polyposis (FAP) is an autosomal dominant disorder which typically presents with colorectal cancer in early adult life secondary to extensive adenomatous polyps of the colon. Gardner's syndrome is a variant of FAP in which desmoid tumors, osteomas and pigmented retinal lesions occur together with intestinal manifestations. The APC gene (adenomatous polyposis coli) at 5q21 is a tumor suppressor gene which is mutant in FAP. PATIENT: A 36 year old woman presented with a history of polyposis ventriculi, ovarian desmoid cysts, and disseminated desmoid tumors. Her familial history was unremarkable. On admission she complained weight gain, secondary amenorrhea, and episodes of hypertension followed by paroxysmal headache. RESULTS: Elevated urinary free cortisol (878 microg/24h), suppressed basal ACTH (< 5 pg/ml) and insuppressible serum cortisol after low dose dexamethasone (189 ng/ml) revealed adrenal Cushing's syndrome. Abdominal NMR showed an adrenal mass two centimeter in diameter with inhomogeneous contrast enhancement. Unilateral adrenalectomy was performed and an adrenal adenoma was diagnosed by histological criteria. For mutational detection DNA from peripheral blood leucocytes was extracted. A protein truncation test was performed, which revealed a termination mutation between codon 1099 and 1623 of the APC gene. Direct sequencing showed a point mutation in exon 15 of the APC gene at position 1542 (CAG --> TAG). This region is known to be altered in patients with extraintestinal manifestation of FAP. CONCLUSION: In patients with Gardner's syndrome adrenal tumors leading to hormonal excess should be considered. Whether mutations in the APC gene have implications in sporadic adrenal tumorigenesis needs to be proven. PMID- 11196456 TI - Risk factors associated with persistent postoperative hypertension in Cushing's syndrome. AB - The aim of the present study was to assess the long-term results of adrenalectomy and to evaluate potential risk factors for the persistence or recurrence of hypertension. Forty-five patients with Cushing's syndrome caused by benign cortisol-producing adrenocortical adenomas were evaluated before and for a period of 1 year after surgical cure. When the patients were classified into two groups according to whether their preoperative BP was more (HBP group) or less (NBP group) than 140/90 mmHg, the BP level was found to be continuously higher in the HBP group than in the NBP group during the year after surgery. This finding suggests that the preoperative BP level in Cushing's syndrome may be a determinant factor for persistent hypertension after surgery (P<0.05). In addition, a correlation was found between postoperative BP level and duration of hypertension (P<0.05), but no relationships were found between postoperative BP levels and other factors, including age, BMI, tumor size, serum cortisol, aldosterone, potassium, total cholesterol, or glucose levels. The above findings indicate that intensive control of preoperative BP to maintain it below 140/90 mmHg with antihypertensive medication is a very important means of improving prognosis for postoperative BP. Immediate diagnosis and surgical treatment to reduce the duration of hypertension are also crucial for the long-term BP prognosis. PMID- 11196457 TI - Two novel mutations in splice donor sites of CYP11B1 in congenital adrenal hyperplasia due to 11beta-hydroxylase deficiency. AB - We present an in vivo and in vitro study of congenital adrenal hyperplasia in a patient with 11beta-hydroxylase deficiency. Genetic analysis showed two new base substitutions of CYP11B1, a conservative transition at the last base of exon 5, and a IVS8+4A-->G transition in intron 8. Difficulties with suppressive therapy resulted in severe hypertension. A laparoscopic adrenalectomy was decided which lead to normalization of blood pressure. In vitro, steroidogenesis by adrenal cells showed no measurable 11beta-hydroxylase activity. Analysis of CYP11B1 mRNA by RT-PCR and sequencing showed expression of a mRNA which lacked exon 8, presumably resulting from the intron 8 mutation. In addition a highly truncated mRNA was detected corresponding to exons 1, 2, 8, 9, with the loss of exons 3-7, presumably related to the exon 5 mutation. Western blot analysis showed a shorter CYP11B immunoreactive band of 43 kDa, consistent with truncation of exon 8. Thus adrenalectomy in this patient allowed effective treatment of severe hypertension and helped to understand the mechanisms of two novel mutations responsible for aberrant splicing of CYP11B1. PMID- 11196458 TI - The application of high density microarray for analysis of mitogenic signaling and cell-cycle in the adrenal. AB - Angiotensin II (AII) binds to specific G-protein coupled receptors and is mitogenic in adrenal, liver epithelial, and vascular smooth muscle cells. The H295R human adrenocortical cell line, which expresses AII receptors predominantly of the AT1 subclass, proliferates in response to treatment with AII. The induction and maintenance of cellular proliferation involves a precisely coordinated induction of a variety of genes. As the human genome sequencing projects near completion a variety of high throughput technologies have been developed in order to create dynamic displays of genomic responses. One high throughput method, the gridded cDNA microarray has been developed in which immobilised DNA samples are hybridized on glass slides for the identification of global genomic responses. For this purpose high precision robotic microarrayers have been developed at AECOM. The cyclin D1 gene, which encodes the regulatory subunit of the cyclin D1-dependent kinase (CD1K) required for phosphorylation of the retinoblastoma protein (pRB), was induced by AII in H295R cells. Abundance of the cyclin D1 gene is rate-limiting in G1 phase progression of the cell-cycle in a variety of cell types. AII induced cyclin D1 promoter activity through a c-Fos and c-Jun binding sequence at -954 bp. Theabundance of c-Fos within this complex was increased by AII treatment. Analysis of AII signaling in adrenal cells by cDNA microarray demonstrated an induction of the human homologue of Xenopus XPMC2 (HXPMC2). The cDNA for XPMC2 was previously shown to rescue mitotic catastrophe in mutant S. Pombe defective in cdc2 kinase function. Further studies are required to determine the requirement for cyclin D1 and XPMC2H in AII-induced cell-cycle progression and cellular proliferation in the adrenal. PMID- 11196459 TI - Signal transduction in G0/G1-arrested mouse Y1 adrenocortical cells stimulated by ACTH and FGF2. AB - In G0/G1 cell cycle arrested mouse Y1 adrenocortical tumor cells ACTH39, a weak mitogen and strong anti-mitogenic agent, blocks FGF2 mitogenic activity at G1 phase, keeping untouched ERK-MAPK activation and c-Fos protein induction. Here we report two anti-mitogenic mechanisms initiated in ACTH receptors and mediated by cAMP/PKA: a) post-transcriptional down regulation of c-Myc protein; b) dephosphorylation of AKT/PKB. In Y-1 cells the activity of the Mad/Max/Myc network of transcription factors seems to be regulated by c-Myc levels. FGF2 induces c-myc gene and stabilizes c-Myc protein by a process dependent on ERK MAPK (PD98059 sensitive), but not on PI3K (Wortmannin resistant). ACTH39, on the other hand, causes rapid decrease in c-Myc levels induced by FGF2 in wild type Y1 cells, but not in PKA-deficient Y1 clones. The ACTH inhibition of DNA synthesis stimulated by FGF2 is reversed by transient transfection and induction of the MycER chimera (fusion of c-Myc and estrogen-receptor), suggesting that c-Myc down regulation is an efficient anti-mitogenic mechanism activated by ACTH. Y1 cells display high constitutive levels of AKT/PKB, that is dependent on elevated Ras x GTP. FGF2 up regulates Ras x GTP, PI3K and AKT/PKB. ACTH antagonizes this mitogenic effect of FGF2, promoting rapid dephosphorylation of AKT/PKB. PMID- 11196460 TI - Neurotransmitters and neuropeptides in the differential regulation of steroidogenesis in adrenocortical-chromaffin co-cultures. AB - Adrenocortical steroidogenesis is regulated in addition to a central regulation via the hypothalamus-pituitary-adrenal axis by intra-adrenal mechanisms involving the adrenal medulla. We could previously show that adrenocortical steroidogenesis is stimulated by co-culturing bovine adrenocortical cells with medullary chromaffin cells. This stimulation was due to soluble factors released from the chromaffin cells under basal, unstimulated conditions and involved the increased expression of P450 enzymes, StAR and de novo protein synthesis. In the present study we analyzed the differential regulation of the three cortical zones and characterized secretagogues involved in this stimulation. While cortisol and androstenedione release were increased 10 fold by incubation with chromaffin cell conditioned medium, aldosterone secretion was not influenced. 80% of the stimulation proved to be due to adrenomedullary epinephrine, norepinephrine, ACTH, PACAP and PG-dependent mechanisms. Other adrenomedullary secretory products, serotonin, Met-enkephalin, Leu-enkephalin, galanin, CGRP, substance P, VIP or NPY did not stimulate steroidogenesis in this system. Our data show that adrenomedullary cells differentially regulate the three adrenocortical zones. This stimulation predominantly depended on epinephrine, norepinephrine, PACAP, and ACTH released from the chromaffin cells and prostaglandin-dependent mechanisms such as interleukin-1. PMID- 11196461 TI - Paracrine control of the adult adrenal cortex vasculature by vascular endothelial growth factor. AB - The extensive vascular network that irrigates the adult adrenal cortex is essential for both the delivery of oxygen and nutrients to glandular steroidogenic cells and for the rapid and efficient export of corticosteroid products from these cells into the blood flow. During experimental and pathological changes in adrenal cortex size caused by ACTH overproduction or deficiency, the vasculature evolves in a coordinated manner with the mass of glandular cells so that blood vessel formation/regression and cortical gowth/atrophy are respectively synchronized. In addition to its previously reported expression in human fetal adrenocortical cells, the angiogenic factor VEGF-A appears also to be strongly expressed by both glomerulosa and fasciculata cells of the adult bovine adrenal cortex, when the endothelium is quiescent. Moreover, the expression of the two major transcripts encoding the 121 and the 165 amino acid-long isoforms of VEGF-A was observed to be rapidly (within 2-4 h) up-regulated (2-3 fold) by ACTH in primary cultures of bovine fasciculata and glomerulosa cells. The expression of the signalling VEGF receptors R1 (flt-1) and R2 (flk-1) was restricted to the endothelial cells of the cortex whereas neuropilin-1 was expressed by both endothelial and steroidogenic cells. This suggests that, under the control of the pituitary hormone ACTH, VEGF exerts a paracrine control over the vasculature of the adult adrenal cortex. Given its known effects as an anti-apoptotic agent and an inducer of endothelial fenestration, VEGF is likely to play a role in the maintenance of the dense and fenestrated vascular bed of the adrenal cortex. The vasculature thus appears as an important secondary target of ACTH action in the physiological control of adrenal cortex homeostasis. PMID- 11196462 TI - Expression and regulation of BCL-2 family genes in human adrenocortical adenomas in comparison with adrenal hyperplasia of Cushing's disease. AB - The significance of increases in the expression of apoptosis-suppressing genes such as bcl-2 and mcl-1/EAT in human adrenal tumors has not yet been fully elucidated. Furthermore the roles of these genes in cell proliferation may involve interaction with steroidogenesis in the tumors via intracellular second messengers. Cyclic AMP (cAMP) caused human adrenocortical H295R cells to overexpress hCYP17 resulting in hypersecretion of cortisol. At the same time, however, expression of bcl-2, which has a cAMP response element (CRE), was not affected. Furthermore, in vivo Bcl-2 protein analysis showed its down-regulation in adrenal hyperplasia of Cushing's disease despite ACTH stimulation. Exogenous addition of glucocorticoid did not affect the expression of bcl-2 family genes. Expressions of Mcl-1/EAT and Bax did not differ markedly among human adrenal glands affected by various pathologies. In conclusion the down-regulation of Bcl 2 in Cushing's disease did not agree with no induction of this gene by cAMP in H295R cells, suggesting that expression of Bcl-2 protein was not regulated mainly by cAMP-protein kinase (PKA) pathways in human adrenal hyperplasia. PMID- 11196463 TI - p53 and Ki67 in adrenocortical tumors. AB - The p53 tumor-supressor gene has been reported as the most frequent genetic abnormality seen in human malignancies. Here we studied immunohistochemically the expression of p53 in a large series of adrenocortical tumors. The proliferative activity was assessed by the expression of Ki67. Tumor material consisted of 60 adrenocortical adenomas and 27 adrenocortical carcinomas. A tumor was scored as positive for p53 if more than 10% of the cells showed nuclear staining. All adrenocortical adenomas were negative for p53 and the percentage of Ki67 positive cells was mostly 1-2% but never exceeded 5%. Hormonal activity did not reflect the proliferation index. Adrenocortical carcinomas, however, behaved differently depending on hormonal activity. 10/13 of non-functional , 0/3 Conn's, 3/7 Cushing's and 3/4 virilizing carcinomas were positive for p53. The proliferative activity was also higher in non-fuctional carcinomas compared with hormonally active tumors. Our data show that majority of adrenocortical carcinomas are positive for p53, whereas all adenomas are negative. Hormonal activity of carcinomas reflects both p53 status and proliferation index. Thus, immunohistochemical levels of p53 and Ki67 are higher in hormonally inactive adrenocortical carcinomas. PMID- 11196464 TI - Expression of vascular endothelial growth factor in human adrenals. AB - Angiogenesis is an important component in many biological processes and also in pathologic conditions including neoplastic diseases. Vascular endothelial growth factor (VEGF) is a secreted endothelial cell-specific growth factor, which is induced by tissue hypoxia and is angiogenic in vivo. Adrenal gland is a well vascularized organ, and the roles of VEGF in normal adrenal and in adrenal tumorigenesis is not well characterized. We therefore investigated VEGF mRNA expression in normal human adrenals and in cultured adrenocortical cells. VEGF mRNA was constantly expressed in normal adrenals as well as in cultured adrenocortical cells. The mRNA levels were increased after 24h stimulation with either ACTH or cAMP. The effect of cAMP was dose-dependent. This suggests that ACTH-induced VEGF mRNA expression is mediated via protein kinase A dependent pathway. PMID- 11196465 TI - Role of ERK/MAP kinase in mitogenic interaction between ACTH and FGF2 in mouse Y1 adrenocortical tumor cells. AB - In G0/G1 cell cycle-arrested Y1 adrenocortical cells FGF2 is a strong mitogen, whereas ACTH39 can be a weak mitogen or a strong anti-mitogenic agent. Phosphorylated ERK1/2-MAP kinases are undetectable by Western and immunocitochemistry assay in G0/G1-arrested Y1 adrenal cells. Cell entry into S phase linearly correlates with migration of phosphorylated ERK to nucleus. FGF2 rapid and strongly triggers transient phosphorylation of ERK1/2, whereas ACTH39 is a poor ERK1/2 activator. But, the MEK1 inhibitor, PD98059 (50microM), inhibits cFos and cyclin D1 induction and DNA synthesis stimulation by both ACTH39 and FGF2, suggesting that ERK1/2 activation mediates the strong and the weak mitogenic effect of, respectively, FGF2 and ACTH39. In addition, ACTH39 antagonizes the FGF2 mitogenic effect keeping untouched ERK1/2 activation, c-Fos and cyclin D1 induction. PMID- 11196466 TI - Regulation of MAPK activity in response to dietary sodium in the rat adrenal gland. AB - Stimulation of aldosterone biosynthesis by angiotensin II (AII) is thought to be mediated via the PLC, IP3 and intracellular calcium signalling pathway. MAPK (p42/p44) is involved in cell proliferation, and is also activated by AII, but its role in the adrenal response to dietary sodium is unclear. To study the relationship between AII receptor (ATR), MAPK and PKC isoforms, PKCalpha and PKCepsilon, mature Wistar rats were maintained on low or high sodium diets for 1 week. In adrenals from animals on a sodium deplete diet, total ligand binding to both ATR subtypes decreased in the zona glomerulosa (ZG). Under these conditions, active MAPK in the ZG decreased paralleling a decrease in active PKCalpha. In the inner zones (IZ), largely reflecting medullary events, low sodium did not affect MAPK activity. However active PKCalpha decreased. In adrenals from sodium-loaded animals, type 2 ATR (AT2R) binding was reduced in the ZG, while type 1 ATR (AT1R) increased in the IZ. Active MAPK increased in ZG, as did active PKCalpha and PKCepsilon. In IZ, ERK, PKCalpha and PKCepsilon were unchanged. These results suggest that in the ZG and IZ, two different modes of MAPK regulation may exist, utilising different PKC isoforms. PMID- 11196467 TI - Adrenal tumorigenesis targeted by the corticotropin-regulated promoter of the aldo-keto reductase AKR1B7 gene in transgenic mice. AB - Studies of ACTH functions in adrenal steroidogenesis have been facilitated by the availability of immortalized mouse adrenocortical Y1 cells. In order to obtain alternative cell lines with a more differentiated zona fasciculata (ZF) phenotype we used targeted tumorigenesis strategy. We have generated transgenic mice expressing the SV40 T antigen under the control of the ACTH-dependent promoter for the AKR1B7/MVDP gene (aldo-keto reductase 1B7/mouse vas deferens protein), which encodes an enzyme responsible for detoxifying isocaproaldehyde, the product of side-chain cleavage of cholesterol generated by steroidogenesis. Our previous data indicated that in the mouse adrenal, AKR1B7 expression was restricted to the ZF and that a 0.5-kb promoter region was able to target specific adrenal expression in transgenic mice. In situ hybridization analyses indicate that AKR1B7 expression during fetal and post-natal periods paralleled the onset of glucocorticoid synthesis and the development of ZF. In transgenic mice, ACTH control and developmental programming of the CAT gene driven by the 0.5-kb promoter followed endogenous gene regulation. Then transgenic mice harboring the 0.5-kb/SV40 T antigen construct were generated and two founders out of three developed adrenal tumors. Cells derived from the tumor of founder 1 (ATC1) were grown in presence of forskolin to maintain ACTH receptor expression and were tested for ACTH responsiveness by immunocychemistry and northern blot analyses. Even after several passages, the ACTH induced AKR1B7 and P450c11beta mRNAs accumulations were similar to that observed in mouse primary adrenocortical cell cultures. Our findings suggest that ATC1 cells have conserved essential features of ZF cells. In order to achieve complete characterization of these cells further analyses are currently performed to investigate their steroidogenic activity. PMID- 11196468 TI - Daily regeneration of rat adrenocortical cells: circadian and zonal variations in cytogenesis. AB - Daily regeneration of rat adrenocortical cells were investigated in terms of circadian and zonal variations by following the cells at the DNA-synthesizing stage. An S-phase was assessed by 5-bromo-2'-deoxyuridine (BrdU) incorporation into the cell-nuclei and/or by visualizing proliferating cell nuclear antigen. The BrdU-positive cells were observed throughout the day mainly in two regions of the adrenal cortex, i.e. the innermost portion of the zona glomerulosa and the outermost portion of the zona fasciculata. Cells only in a latter region showed a distinct circadian rhythm of cell proliferation with a peak at 3-4 a.m. A remarkable rise in the plasma adrenocorticotropin (ACTH) concentration preceded such an increase in the cell proliferation by about 4 hours. This phenomenon could be mimicked by raising the plasma ACTH concentration by the administration of Cortrosyn Z or metyrapone. Angiotensin II-stimuli induced by Na-deficiency increased the proliferation of zona glomerulosa cells in the former region at 6 7p.m without significant effects on that of the zona fasciculata cells in the latter region. Thus at least two sites, which respond differentially to the day/night cycle and circulating hormone levels, exist in rat adrenal cortex being responsible for the cytogenesis in this endocrine organ. PMID- 11196469 TI - Transforming growth factor beta1: implications in adrenocortical tumorigenesis. AB - TGFbeta1, a multifunctional growth modulator, inhibits the proliferation of epithelial cells. TGFbeta1 signaling is dependent on the heterodimerization of the TGFbeta1 receptor II (TGFbeta1RII) with the TGFbeta1 receptor I (TGFbeta1RI). The cytoplasmic proteins Smads are the mediators of the TGFbeta1 signal. TGFbeta1 regulates adult and fetal adrenal growth and function. Previously we have shown by Northern analysis that TGFbeta1mRNA was well expressed in normal adrenal and in adrenocortical adenomas but reduced in carcinomas. To investigate whether TGFbeta1 receptors may act as tumor suppressors of adrenal tumorigenesis, 16 adenomas and 12 carcinomas were studied. We have used SSCP analysis to scan for inactivating mutations in carcinomas. All tumor samples were negative for somatic alterations of both genes. A competitive RT-PCR system was developed to compare the levels of expression of TGFbeta1, TGFbeta1R-I and TGFbeta1R-II, Smad-2 and Smad-4 genes in all tumors. In our study, we confirmed the presence of reduced levels of TGFbeta1 in carcinomas. On the contrary, Smad-4 gene levels were elevated in carcinomas when compared to that of adenomas. No significant differences were observed in gene expression of TGFbeta1RI and Smad-2. Our results suggest that mutations of TGFbeta1 receptors appear not to be involved in adrenal tumorigenesis. Adrenal carcinomas showed a significant reduction of the TGFbeta1 mRNA levels but on the contrary Smad 4 mRNA levels were significantly increased. PMID- 11196470 TI - ACTH inhibits A Ras-dependent anti-apoptotic and mitogenic pathway in mouse Y1 adrenocortical cells. AB - Mouse Y1 adrenocortical tumor cells harbor amplified and overexpressed c-Ki-ras gene, displaying relatively high constitutive levels of Ras x GTP. Here we report that Y1 cells also constitutively display high levels of phosphorylated AKT/PKB, that are dependent on Ras x GTP and PI3K. ACTH rapidly causes dephosphorylation of AKT/PKB in a cAMP/PKA dependent maner. This ACTH inhibition of the anti apoptic and mitogenic AKT/PKB pathway is likely to be relevant in ACTH growth inhibitory effects in Y-adrenocortical cells. PMID- 11196471 TI - Mechanisms of epigenetic silencing of the c21 gene in Y1 adrenocortical tumor cells. AB - We utilized Y1 adrenocortical carcinoma cell line as a model system to dissect the events regulating epigenomic gene silencing in tumor cells. We show here that the chromatin structure of c21 gene is inactive in Y1 cells and that it could be reconfigured to an active form by either expressing antisense mRNA to DNA methyltransferase 1 (dnmt1) or an attenuator of Ras protooncogenic signaling hGAP. Surprisingly however, the known inducer of active chromatin structure the histone deacetylase inhibitor trichostatin A TSA fails to induce expression of c21. These results suggest that the primary cause of c21 gene silencing is independent of histone deacetylation. We present a model to explain the possible roles of the different components of the epigenome and the DNA methylation and demethylation machineries in silencing c21 gene expression. PMID- 11196472 TI - Transplantation of normal and genetically modified adrenocortical cells. AB - Cell transplantation techniques have been applied to the study of the biology of the adrenal cortex and to adrenocortical cell proliferation, differentiation, and senescence. Primary bovine adrenocortical cells, primary human adrenocortical cells and genetically modified bovine adrenocortical cells have been transplanted. Successful methods include transplantation of cells beneath the kidney capsule and several subcutaneous cell transplantation procedures. In successful transplants the cells form a functional vascularized tissue structure that allows the host animals to survive adrenalectomy. We show here that subcutaneous cell transplantation does not depend on embedding cells in collagen gel before introduction into the host animal. Subcutaneous transplants secrete both cortisol and aldosterone. However, the variability of plasma aldosterone levels indicates that the factors that determine glomerulosa-type and fasciculata type cell function in transplant tissues are not well understood. PMID- 11196474 TI - Adrenocortical and gonadal differentiation regulated by transcription factors, Ad4BP/SF-1 (NR5A1) and Dax-I (NROB1). PMID- 11196473 TI - Regulation of human CYP11B2 and CYP11B1: comparing the role of the common CRE/Ad1 element. AB - In humans, the final steps in corticosteroid production results from the activity of aldosterone synthase in the glomerulosa and 11beta-hydroxylase in the fasciculata. The regional expression of these isozymes is believed to result from transcriptional regulation of the aldosterone synthase (CYP11B2) and 11beta hydroxylase (CYP11B1) genes. Previous studies suggest that the primary cis element needed for agonist enhanced transcription of the CYP11B genes shares high sequence similarity to a consensus cAMP Response Element (CRE). Here the role of the CRE/Adl was studied. Reporter constructs prepared with the 5'flanking DNA of hCYP11B2 and hCYP11B1 were transfected into NCI-H295R (H295R) adrenocortical tumor cells. Both hCYP11B2 and hCYP11B1 driven reporter constructs responded in a similar manner to treatment with angiotensin II, potassium, dbcAMP, or forskolin. Mutation of the hCYP11B1 CRE/Adl element decreased basal reporter expression and decreased response to agonist. Mutation of the hCYP11B2 CRE/Adl element caused a loss of basal expression but retained response to agonist suggesting a role for other cis-elements in hormonal regulation of hCYP11B2. In addition, both cis elements were able to form complexes with in vitro prepared CRE binding (CREB) protein, activating transcription factor (ATF)-1 and ATF-2 in mobility shift assays. However, only the ATF-2 complex migrated similarly to a complex seen using H295R nuclear extract. Taken together these data suggest that the CRE/Adl element plays an important role in the transcriptional regulation of both hCYP11B genes but does not play an important role in the regional distribution of the two isozymes within the adrenal. PMID- 11196475 TI - The AT2 receptor of angiotensin II and apoptosis in human fetal adrenal gland. PMID- 11196476 TI - Adrenocortical expression of MnSOD. AB - The mitochondrial matrix antioxidant manganese superoxide dismutase (MnSOD) is part of a cascade of components that protects the cell from cytotoxic reactive oxygen species (ROS) and previous investigations have predominately concentrated on this role. However, recent studies on the roles of redox state and ROS suggest that they may have a role in cellular regulation. Using a cDNA clone we generated, northern blot analysis localised the expression of MnSOD predominantly to the zona fasciculata and reticularis (zfr) in rat adrenals. To test whether this correlated with MnSOD activity, assays were conducted on adrenal tissue from rats maintained on a low sodium diet or betamethasone treated and compared with that of untreated controls. MnSOD activity was enhanced in zfr adrenal mitochondria from rats that were ACTH treated or on a low sodium diet. Betamethasone had no effect, and cytosolic/membrane SOD activities were unchanged by all of the treatments. The identification of MnSOD as a hormone inducible component in the adrenal cortex is consistent with the concept that the redox state and/or ROS are involved in the specific regulation of zfr function. PMID- 11196477 TI - Captopril effects on the rat adrenal cortex. PMID- 11196478 TI - Zonal differentiation in the rat adrenal cortex. AB - The factors that establish and maintain adrenocortical zonation are poorly understood. The capsular adrenal gland of the rat has been shown to develop into a functionally zoned tissue in autotransplanted glands in vivo. To examine this in vitro, capsular gland preparations (largely glomerulosa (zg) with some fasciculata (zf) were cultured in vitro in Eagles MEM (3.6mM K+) for 14 days. Zonal differentiation was determined by immunocytochemical localisation of inner zone antigen (IZA, zf/reticularis specific) and Pref-1 (zg specific). In the absence of further additions these preparations invariably maintained a good zonal arrangement of zg and zf over the whole period, though without significant cellular proliferation. Neither the daily addition of the stimulants, maximally 8.3mM potassium, 1nM ACTH, or 100nM angiotensin II (AII), or the AII type 1 receptor antagonist losartan (10microM) had any significant effect on the glands intrinsic capacity to maintain zonation in vitro. Aldosterone output declined rapidly under control conditions (3.6mM K+), but was stimulated by AII, or high K+ reaching a maximum after 7 days, and thereafter declined. However at higher K+ conditions (5.6mM) aldosterone was not supported by angiotensin II. Corticosterone secretion increased autonomously after 2 days in 3.6mM K+ then declined. At higher K+ conditions corticosterone rapidly declined. The factors studied had no effect on the inherent property of the adrenal gland to express the zg or zf phenotype. However the functional steroidogenic capacity of the adrenocortical cells was affected in a highly specific and complex manner by the added stimulants. PMID- 11196479 TI - Neural modulation of regenerating adrenal transplants. PMID- 11196480 TI - Role of phosphorylation, gene dosage and Dax-1 in SF-1 mediated steroidogenesis. AB - The mechanisms by which SF-1 (Steroidogenic Factor-1) and Dax-1 (Dosage-sensitive sex reversal-Adrenal hypoplasia congenita critical region on the X chromosome) dictate adrenal-specific transcriptional programs are the focus of this laboratory. SF-1-mediated transcription is upregulated by phosphorylation of serine 203 located in the hinge region of SF-1. An SF-1S203A mutant attenuates SF 1 activation, while substitution of S203 with a charged aspartate (SF-1S203D) results in a dose dependent increase in SF-1 mediated transcription. Ser203 serves as a substrate for Erk2 in vitro and is critical for activation of SF-1 by multiple components of the MAPK pathway. Isoelectric focusing demonstrates multiple immuno-reactive SF-1 species in mouse adrenal and NCI-H295A cell extracts. We propose that differential phosphorylation of SF-1 by various mitogens serves to couple extracellular signals to adrenal-specific transcriptional programs. Mouse studies utilizing SF-1 heterozygous mice explore the in vivo role of SF-1 levels, SF-1 phosphorylation and SF-1 interaction with Dax-1 in adrenal steroidogenesis. SF-1 heterozygous mice exhibit a marked decrease in baseline and post-stress corticosterone with a concomitant increase in ACTH. The role of Dax-1 in these SF-1 dependent processes is explored in compound SF-1 (+/-)/Dax-1 KO mice that exhibit an increase in basal corticosterone and a decrease in basal ACTH compared to simple SF-1 (+/-) mice. These finding are consistent with an inhibitory role for Dax-1 in SF-1 mediated transcription. Mice that express epitope tagged SF-1 (wild type, SF-1S203A and SF 1S203D) are being used to rescue the heterozygous adrenal phenotype and to determine the in vivo role of SF-1 phosphorylation in adrenal function. PMID- 11196481 TI - SIK (Salt-inducible kinase): regulation of ACTH-mediated steroidogenic gene expression and nuclear/cytosol redistribution. AB - Possible involvement of salt-inducible kinase (SIK), a serine/threonine protein kinase first cloned from high K+-diet treated rat adrenal glands, in the regulation of steroidogenesis was investigated. Y-1 cells, when treated with ACTH, underwent a rapid change in SIK's mRNA content. It reached the maximum within a few hours and returned to the base after 8 h. In contrast, the levels of mRNAs for CYP11A and StAR protein reached the maxima after 8 h. The SIK's mRNA induction failed to occur in ACTH-, forskolin- or 8-Br-cAMP-treated Kin-7 cells, a mutant cell line of Y-1 with defective cAMP-dependent protein kinase A (PKA). Y 1 cells that overexpress SIK, when treated with ACTH, had significantly repressed levels of mRNAs for CYP11A and StAR protein. Therefore, SIK might have a negative effect on the CYP11A- and StAR protein-gene expression in the early phase of ACTH mediated steroidogenesis. To further explore the mechanisms underlying this phenomenon, we examined intracellular distribution of the green fluorescence protein (GFP)-tagged SIK. When GFP-SIK was introduced into HeLa cells, the fluorescent signals were detected in the nucleus. In Y-1 cells GFP-SIK was detected both in the nucleus and cytosol, and the signal in the former moved to the latter after ACTH-treatment. The nuclear/cytosol re-distribution of GFP-SIK was also observed in forskolin- or 8-Br-cAMP-treated Y-1 cells, but not in Kin-7 cells. These results suggest that the intracellular re-distribution of SIK in Y-1 cells may depend on the cAMP/PKA signaling pathway and has an important regulatory role in the ACTH-mediated steroidogenic gene expression. PMID- 11196482 TI - Farewell to polio in the Western Pacific. PMID- 11196483 TI - The challenges of doing more against malaria, particularly in Africa. PMID- 11196484 TI - Roll back malaria--what are the prospects? PMID- 11196485 TI - Combination therapy for malaria in Africa: hype or hope? AB - The development of resistance to drugs poses one of the greatest threats to malaria control. In Africa, the efficacy of readily affordable antimalarial drugs is declining rapidly, while highly efficacious drugs tend to be too expensive. Cost-effective strategies are needed to extend the useful life spans of antimalarial drugs. Observations in South-East Asia on combination therapy with artemisinin derivatives and mefloquine indicate that the development of resistance to both components is slowed down. This suggests the possibility of a solution to the problem of drug resistance in Africa, where, however, there are major obstacles in the way of deploying combination therapy effectively. The rates of transmission are relatively high, a large proportion of asymptomatic infection occurs in semi-immune persons, the use of drugs is frequently inappropriate and ill-informed, there is a general lack of laboratory diagnoses, and public health systems in sub-Saharan Africa are generally weak. Furthermore, the cost of combination therapy is comparatively high. We review combination therapy as used in South-East Asia and outline the problems that have to be overcome in order to adopt it successfully in sub-Saharan Africa. PMID- 11196486 TI - Comparison of house spraying and insecticide-treated nets for malaria control. AB - The efficacies of using residual house spraying and insecticide-treated nets against malaria vectors are compared, using data from six recent comparisons in Africa, Asia and Melanesia. By all the entomological and malariological criteria recorded, pyrethroid-treated nets were at least as efficacious as house spraying with dichlorodiphenyltrichloroethane (DDT), malathion or a pyrethroid. However, when data from carefully monitored house spraying projects carried out between the 1950s and 1970s at Pare-Taveta and Zanzibar (United Republic of Tanzania), Kisumu (Kenya) and Garki (Nigeria) are compared with recent insecticide-treated net trials with apparently similar vector populations, the results with the insecticide-treated nets were much less impressive. Possible explanations include the longer duration of most of the earlier spraying projects and the use of non irritant insecticides. Non-irritant insecticides may yield higher mosquito mortalities than pyrethroids, which tend to make insects leave the site of treatment (i.e. are excito-repellent). Comparative tests with non-irritant insecticides, including their use on nets, are advocated. The relative costs and sustainability of spraying and of insecticide-treated net operations are briefly reviewed for villages in endemic and epidemic situations and in camps for displaced populations. The importance of high population coverage is emphasized, and the advantages of providing treatment free of charge, rather than charging individuals, are pointed out. PMID- 11196487 TI - Spatial targeting of interventions against malaria. AB - Malaria transmission is strongly associated with location. This association has two main features. First, the disease is focused around specific mosquito breeding sites and can normally be transmitted only within certain distances from them: in Africa these are typically between a few hundred metres and a kilometre and rarely exceed 2-3 kilometres. Second, there is a marked clustering of persons with malaria parasites and clinical symptoms at particular sites, usually households. In localities of low endemicity the level of malaria risk or case incidence may vary widely between households because the specific characteristics of houses and their locations affect contact between humans and vectors. Where endemicity is high, differences in human/vector contact rates between different households may have less effect on malaria case incidences. This is because superinfection and exposure-acquired immunity blur the proportional relationship between inoculation rates and case incidences. Accurate information on the distribution of malaria on the ground permits interventions to be targeted towards the foci of transmission and the locations and households of high malaria risk within them. Such targeting greatly increases the effectiveness of control measures. On the other hand, the inadvertent exclusion of these locations causes potentially effective control measures to fail. The computerized mapping and management of location data in geographical information systems should greatly assist the targeting of interventions against malaria at the focal and household levels, leading to improved effectiveness and cost-effectiveness of control. PMID- 11196488 TI - Molecular entomology and prospects for malaria control. AB - During the past decade, the techniques of molecular and cell biology have been embraced by many scientists doing research on anopheline vectors of malaria parasites. Some of the most important research advances in molecular entomology have concerned the development of sophisticated molecular tools for procedures such as genetic and physical mapping and germ line transformation. Major advances have also been made in the study of specific biological processes such as insect defence against pathogens and the manner in which malaria parasites and their anopheline hosts interact during sporogony. One of the most important highlights of this research trend has been the emergence during the past year of a formal international Anopheles gambiae genome project, which at present includes investigators in several laboratories in Europe and the USA. Although much of this molecular research is directed towards the development of malaria control strategies that are probably many years from implementation, there are some important areas of molecular entomology that may have a more near-term impact on malaria control. We highlight developments over the past decade in three such areas that we believe can make important contributions to the development of near term malaria control strategies. These areas are anopheline species identification, the detection and monitoring of insecticide susceptibility/resistance in wild anopheline populations and the determination of the genetic structure of anopheline populations. PMID- 11196489 TI - Entering the post-genomic era of malaria research. AB - The sequencing of the genome of Plasmodium falciparum promises to revolutionize the way in which malaria research will be carried out. Beyond simple gene discovery, the genome sequence will facilitate the comprehensive determination of the parasite's gene expression during its developmental phases, pathology, and in response to environmental variables, such as drug treatment and host genetic background. This article reviews the current status of the P. falciparum genome sequencing project and the unique insights it has generated. We also summarize the application of bioinformatics and analytical tools that have been developed for functional genomics. The aim of these activities is the rational, information based identification of new therapeutic strategies and targets, based on a thorough insight into the biology of Plasmodium spp. PMID- 11196490 TI - Using a geographical information system to plan a malaria control programme in South Africa. AB - INTRODUCTION: Sustainable control of malaria in sub-Saharan Africa is jeopardized by dwindling public health resources resulting from competing health priorities that include an overwhelming acquired immunodeficiency syndrome (AIDS) epidemic. In Mpumalanga province, South Africa, rational planning has historically been hampered by a case surveillance system for malaria that only provided estimates of risk at the magisterial district level (a subdivision of a province). METHODS: To better map control programme activities to their geographical location, the malaria notification system was overhauled and a geographical information system implemented. The introduction of a simplified notification form used only for malaria and a carefully monitored notification system provided the good quality data necessary to support an effective geographical information system. RESULTS: The geographical information system displays data on malaria cases at a village or town level and has proved valuable in stratifying malaria risk within those magisterial districts at highest risk, Barberton and Nkomazi. The conspicuous west-to-east gradient, in which the risk rises sharply towards the Mozambican border (relative risk = 4.12, 95% confidence interval = 3.88-4.46 when the malaria risk within 5 km of the border was compared with the remaining areas in these two districts), allowed development of a targeted approach to control. DISCUSSION: The geographical information system for malaria was enormously valuable in enabling malaria risk at town and village level to be shown. Matching malaria control measures to specific strata of endemic malaria has provided the opportunity for more efficient malaria control in Mpumalanga province. PMID- 11196491 TI - The fate of sporozoites. PMID- 11196492 TI - Demonstration of a persisting exo-erythrocytic cycle in Plasmodium cynomolgi and its bearing on the production of relapses. 1948. PMID- 11196493 TI - Malaria control stymied in 2010, mastered in 2025. PMID- 11196495 TI - Malaria--first, roll back expectations. PMID- 11196494 TI - Roll back malaria in sub-Saharan Africa? PMID- 11196496 TI - Roll back malaria: technically feasible or just politically correct? PMID- 11196497 TI - Roll back malaria is unarguably both necessary and possible. PMID- 11196498 TI - Estimating the number of helminthic infections in the Republic of Cameroon from data on infection prevalence in schoolchildren. AB - INTRODUCTION: The prevalence of infection with helminths is markedly dependent on age, yet estimates of the total number of infections are typically based on data only from school-aged children. Such estimates, although useful for advocacy, provide inadequate information for planning control programmes and for quantifying the burden of disease. Using readily available data on the prevalence of infection in schoolchildren, the relation between the prevalence of infection in school-aged children and prevalence in the wider community can be adequately described using species-specific models. This paper explores the reliability of this approach to predict the prevalence infection in the community and provides a model for estimating the total number of people infected in the Republic of Cameroon. METHODS: Using data on the prevalence of helminthic infection in school aged children in Cameroon, the prevalence of infection in pre-school children and adults was estimated from species-specific linear and logistic regression models developed previously. The model predictions were then used to estimate the number of people infected in each district in each age group in Cameroon. RESULTS: For Cameroon, if only the prevalence of infection in schoolchildren is used, the number of people infected with each helminthic species will be overestimated by up to 32% when compared with the estimates provided by the species-specific models. The calculation of confidence intervals supports the statistical reliability of the model since a narrow range of parameter estimates is evident. Furthermore, this work suggests that estimation of national prevalence of infection and the number infected will be enhanced if data are stratified by age; this model represents a useful planning tool for obtaining more accurate estimates. Estimates based on data aggregated from three geographical levels (district, regional, and national) show that summarizing prevalence data at the national level will result in biases of up to 19%. Such biases reflect differences in the geographical distribution for the prevalence of each species. DISCUSSION: Developing more accurate estimates requires a better understanding of the differences in the spatial heterogeneity of each species and also better methods of incorporating this information when making estimates. PMID- 11196499 TI - Safety of community drinking-water and outbreaks of waterborne enteric disease: Israel, 1976-97. AB - Waterborne disease remains a major public health problem in many countries. We report findings on nearly three decades of waterborne disease in Israel and the part these diseases play in the total national burden of enteric disease. During the 1970s and 1980s, Israel's community water supplies were frequently of poor quality according to the microbiological standards at that time, and the country experienced many outbreaks of waterborne enteric disease. New regulations raised water quality standards and made chlorination of community water supplies mandatory, as well as imposing more stringent guidelines on maintaining water sources and distribution systems for both surface water and groundwater. This was followed by improved compliance and water quality, and a marked decline in the number of outbreaks of waterborne disease; no outbreaks were detected between 1992 and 1997. The incidence of waterborne salmonellosis, shigellosis, and typhoid declined markedly as proportions of the total burden of these diseases, but peaked during the time in which there were frequent outbreaks of waterborne disease (1980-85). Long-term trends in the total incidence of reported infectious enteric diseases from all sources, including typhoid, shigellosis, and viral hepatitis (all types) declined, while the total incidence of salmonellosis increased. Mandatory chlorination has had an important impact on improving water quality, in reducing outbreaks of waterborne disease in Israel, and reducing the total burden of enteric disease in the country. PMID- 11196500 TI - Treatment of human African trypanosomiasis. PMID- 11196501 TI - UK report urges screening for "mad sheep" disease. PMID- 11196502 TI - The Uganda Ebola outbreak--not all negative. PMID- 11196503 TI - Malaria drug resistance gene identified. PMID- 11196504 TI - First countries to be recipients of GAVI funds. PMID- 11196505 TI - Doctors' first strike in Republic of Korea likely to end. PMID- 11196506 TI - WHO's plan for Internet health domain halted. PMID- 11196507 TI - A second WHO region declared polio-free. PMID- 11196508 TI - Crawling through the Web: what do our patients find? PMID- 11196509 TI - Factors associated with low bone mineral density in female patients with systemic lupus erythematosus. AB - OBJECTIVE: To study risk factors for low bone mineral density (BMD, g/cm) in patients with systemic lupus erythematosus (SLE). METHODS: Ninety-two consecutive patients with SLE followed by rheumatology faculty between 1997 and 1999 completed a questionnaire regarding lifestyle during the clinic visit, a chart review was performed, and data were collected for the time of the first dual energy x-ray absorptiometry (DXA) examination. Univariate and multivariate statistical analyses were used to assess relationships between various risk factors and BMD. RESULTS: Ninety-eight percent of patients had received prednisone, 51% were postmenopausal (9 of whom received hormone replacement therapy), 68% had received hydroxychloroquine, and 15% were osteoporotic. The following factors were found to be significantly related to lower BMD by univariate analysis: Caucasian race, older age at diagnosis, higher age at the time of the first DXA, longer disease duration, higher cumulative corticosteroid dose, higher SLE Damage Index score, and postmenopausal status. In the multivariate analysis only the following factors were significant: Caucasian race, increased number of pregnancies, postmenopausal status, higher SLE Damage Index, and higher cumulative corticosteroid dose. An unexpected finding was that taking hydroxychloroquine was the only factor associated with higher BMD of the hip and spine in the univariate analysis, and it remained predictive of higher BMD of the hip and spine in the multivariate analysis. CONCLUSION: Hydroxychloroquine appears to protect against low BMD in corticosteroid treated patients with SLE. PMID- 11196510 TI - Systemic vasculitis in patients with hepatitis C. AB - OBJECTIVE: To analyze the main characteristics of patients infected with hepatitis C virus (HCV) presenting with different types of vasculitis syndrome. METHODS: We retrospectively compared 2 groups of patients with HCV presenting with systemic vasculitis: 10 with biopsy proven polyarteritis nodosa-type systemic vasculitis (PAN, Group 1) and 7 with mixed cryoglobulinemia syndrome (MC, Group 2). RESULTS: Patients of Group 1 presented with different features than Group 2: life threatening systemic vasculitis (10 vs 0; p < 0.01), severe multifocal sensorimotor mononeuropathies versus distal moderate sensory polyneuropathies, malignant hypertension (5 vs 0; p = 0.04), cerebral angiitis (2 vs 0), ischemic abdominal pain (2 vs 0), kidney and liver microaneurisms (2 vs 0), increased erythrocyte sedimentation rate and C-reactive protein (7 vs 0; p < 0.01), renal insufficiency (5 vs 0; p = 0.04), HCV genotype 1b (3 vs 6; p = 0.06), and lower activity of chronic hepatitis (p = 0.02). Neuromuscular biopsies showed lesions of vasculitis in all patients, but the type of vasculitis was different in Group 1 compared to Group 2: medium size artery involvement (7 vs 0; p < 0.01), necrotizing vasculitis (10 vs 0; p < 0.01), and mononuclear cell infiltrate in perivascular areas (0 vs 7; p < 0.01). Using prednisone, plasma exchanges, and interferon-alpha, complete recovery was obtained in all PAN-type patients except one. In Group 2 patients, interferon-alpha did not have any effect on the peripheral neuropathy. CONCLUSION: HCV infection may be associated with different types of systemic vasculitis, i.e., polyarteritis nodosa or mixed cryoglobulinemia. Because of differences in clinical and pathological features and therapeutic strategy, PAN-type vasculitis should be distinguished from MC type vasculitis in HCV patients. PMID- 11196511 TI - Abnormal responses to endothelial agonists in Raynaud's phenomenon and scleroderma. AB - OBJECTIVE: To further specify the site of vascular dysfunction in patients with Raynaud's phenomenon (RP) and scleroderma. METHODS: Ten patients with RP and scleroderma and 11 healthy control subjects received brachial artery infusions of sodium nitroprusside, an endothelium independent vasodilator, bradykinin, and substance P while bilateral finger blood flow was measured with venous occlusion plethysmography. RESULTS: Both groups showed vasodilation to sodium nitroprusside. However, in response to the endothelium dependent compounds bradykinin and substance P, the controls showed vasodilation, whereas the patients showed vasoconstriction. CONCLUSION: The vascular defect in RP and scleroderma does not lie at the site of the muscarinic receptor, but possibly in a distal signaling mechanism. PMID- 11196512 TI - Interleukin 16 expression in relation to disease activity in rheumatoid arthritis. AB - OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology characterized by an infiltration of CD4+ T lymphocytes within the rheumatoid synovium. Cytokines have been shown to play a modulatory role in the pathogenesis of RA. We analyzed the expression of a T cell derived cytokine. interleukin 16 (IL-16), in relation to disease activity to characterize its biologic function in RA. METHODS: Secreted IL-16 was measured by enzyme immunoassay in sera and synovial fluids (SF) from 25 patients with RA in comparison to 20 control samples from patients with osteoarthritis (OA). IL-16 expression in peripheral blood mononuclear cells (PBMC) was characterized by flow cytometric analysis after intracellular cytokine staining for IL-16. In synovial tissue specimens, IL-16 mRNA expression was analyzed by real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR). In parallel, expression of IL-16 was localized in synovial tissues by in situ hybridization and immunohistochemistry. Results were analyzed in relation to disease activity. RESULTS: IL-16 was detected at significantly higher levels in sera and SF of patients with RA in comparison to OA (p < 0.001). Flow cytometry of PBMC showed that a great proportion of both CD4+ and CD8+ T cells constitutively expressed the IL-16 protein. In synovial tissues, IL-16 mRNA levels were significantly elevated in comparison to OA controls (p < 0.001). In situ hybridization for IL 16 producing cells revealed a predominant accumulation of IL- 16 positive cells within the inflammatory infiltrates. A significant correlation between IL- 16 expression and local inflammatory activity could not be established (r = 0.27, p = 0.19) by microscopic analysis of the synovial cell infiltrate. In addition, no significant association was observed between serum, SF, and synovial tissue expression of IL-16 and clinical disease activity in RA. CONCLUSION: These data suggest IL-16 might play a role in the pathogenesis of chronic inflammation in RA. The lack of significant correlation between IL-16 expression, clinical disease activity, and local inflammatory activity suggests a regulatory rather than a proinflammatory function for IL-16 in the pathogenesis of chronic synovial inflammation in RA. PMID- 11196513 TI - Seronegative rheumatoid arthritis in elderly and polymyalgia rheumatica have similar patterns of HLA association. AB - OBJECTIVE: To examine whether polymyalgia rheumatica (PMR) and late onset rheumatoid arthritis have identical or similar HLA-DRB1 genetic associations. METHODS: Seventy five PMR cases without evidence of giant cell arteritis were available for study. One hundred seven RA cases were investigated, of which 62 had disease onset after age 60 years. All cases were compared with 145 ethnically matched controls. All cases and controls originated from Lugo, NW Spain. HLA-DRB1 typing was performed on DNA samples using PCR based molecular methods. RESULTS: Early onset RA (< or =40 yrs) was strongly associated with DRB1*04 (DRB1*0401 and *0404). In contrast late onset RA (> or = 60 yrs) was not associated with DRB1*04 but was associated with DRB1*01. Stratification of late onset RA cases by rheumatoid factor status revealed that DRB1*01 was only increased in seropositive RA cases. Late onset seronegative RA cases exhibited increased frequency of DRB1*13/*14; this was also observed in PMR cases where coexistence of GCA had been excluded. CONCLUSION: These data indicate that (1) HLA associations with RA differ with respect to age at disease onset; and (2) seronegative late onset RA and "isolated" PMR have a similar HLA-DRB1 association and may have an identical etiological basis. PMID- 11196514 TI - Clinicopathological findings consistent with primary Sjogren's syndrome in a subset of patients diagnosed with chronic fatigue syndrome: preliminary observations. AB - OBJECTIVE: Some patients diagnosed with chronic fatigue syndrome (CFS) have symptoms commonly observed in Sjogren's syndrome (SS), particularly xerophthalmia and xerostomia, leading to speculation that some patients with CFS might have primary SS or that the 2 disorders share common pathophysiological features. We investigated the prevalence of symptoms of mucosal dryness, salivary gland pathology, lacrimal hyposecretion, and autoantibodies (antinuclear antibody, SSA/SSB) among patients diagnosed with CFS. METHODS: Twenty-five subjects with CFS and 18 healthy control subjects were interviewed and examined, had a Schirmer test and fluorescein tear dilution, and underwent minor salivary gland (MSG) biopsy. Antibody to nuclear antigen as well as anti-La (SSA) and anti-Ro (SSB) antibody were available for subjects with CFS. Pathologists unaware of the subject group assignment examined labial salivary gland biopsy specimens and calculated a standard MSG score for each specimen. RESULTS: Mucosal dryness was reported by 13/25 (52%) subjects with CFS, of which 8 (32%) also had MSG score, low Schirmer test value, and symptoms consistent with primary SS (p = 0.05). No control subject met diagnostic criteria for primary SS. MSG focus scores < or =1 were common among both groups (CFS 14/25; controls 15/18). MSG results without pathological alteration were rare, seen in only one control and no CFS patients. Low Schirmer values were found in 10/25 (40%) CFS patients and 1/18 (6%) control (p = 0.01). CONCLUSION: A subset of patients with CFS may have primary SS. PMID- 11196515 TI - The psychometric properties of patient preferences in osteoporosis. AB - OBJECTIVE: Osteoporosis is a chronic disease manifested by wrist, vertebral, and hip fractures that results in significant morbidity and burden to society. About 30% of postmenopausal women have osteoporosis according to the WHO criteria. Women with one vertebral fracture have a 4-fold increased risk of a subsequent fracture. The goal of treatment is to prevent fractures and improve quality of life. Preferences or utilities are now recommended for incorporating quality of life into evaluations of the cost effectiveness of new therapeutic interventions. We evaluated the psychometric properties of preference based measures in osteoporosis. METHODS: Preference scenarios were constructed with a health state classification system. The reliability and validity of the feeling thermometer and the standard gamble was assessed by interviewing 42 women from 4 different patient groups. The sensitivity to change of the feeling thermometer and standard gamble was compared with the Health Utilities Index Mark 2 (HUI2) and SF-36. All subgroups were reassessed about 2 months after their first interview. RESULTS: Preference measurement was feasible in women of different age groups. The reliability coefficients for health states ranged from 0.65 to 0.87. The preference scores for the marker states demonstrated content validity. Convergent validity of the feeling thermometer was supported by a significant correlation with the HUI2 (r = 0.38, p < 0.05) and the physical health summary of the SF-36 (r = 0.56, p < 0.005). The standard gamble did not correlate with the HUI2 (r = 0.15) or the feeling thermometer (r = 0.09), but correlated with 2 domains of the SF-36. The preference measures were sensitive to change, with the efficiency scores ranging from 0.78 to 1.0. CONCLUSION: Preference measurements in the evaluation of osteoporosis are feasible. The feeling thermometer and standard gamble appear to be related to different aspects of health related quality of life. Both instruments were sensitive to change over a 2 month period. PMID- 11196516 TI - Bone mineral density in patients with psoriatic arthritis. AB - OBJECTIVE: Little information is available concerning bone mass in patients with psoriatic arthritis (PsA): the existence of less severe periarticular osteoporosis is considered possible, but there are no data concerning the existence of systemic osteoporosis. We investigated bone mineral density (BMD) in patients with PsA. METHODS: We studied 186 patients with non-axial PsA and 100 healthy subjects, equally divided into 3 groups: women of child-bearing age, women in menopause, and men. No patient had previously received steroid treatment. In all patients, evaluation was made of disease duration, inflammation indices (erythrocyte sedimentation rate, C-reactive protein), functional indices (Steinbrocker scale), and the Health Assessment Questionnaire (HAQ). BMD was measured by fan-beam x-ray densitometry of the lumbar spine, femur, and total body (evaluating the whole skeleton, as well as the spine, trunk, and upper and lower limbs). Ultrasound densitometry of the heel was also performed. RESULTS: BMD was significantly lower in the arthritic than in the healthy subjects regardless of sex, menopausal status, or age, as expressed in g/cm2 (lumbar spine 1.112 vs 1.326; femoral neck 0.870 vs 1.006; total body 1.125 vs 1.203) or by T and Z scores (lumbar T = -1.36, Z = -0.98; femoral neck T = -1.12, Z = -0.83; total body T = -1.09, Z = -0.65). Ultrasound densitometry of the heel was similarly altered (stiffness 96 vs 77; T -1.78; Z -1.29). Among the PsA patients, demineralization in at least one skeletal region was observed in 67% of premenopausal women (marked in 11%), 100% of postmenopausal women (marked in 47%), and 80% of the men (marked in 29%). In premenopausal women, demineralization did not correlate with the disease variables; in postmenopausal women and the men, it correlated with a decline in the functional indices and the HAQ score. This was confirmed by analysis of the relative risk of osteoporosis expressed in odds ratios (HAQ: 1.6; age: 1.4; years since menopause: 1.7). CONCLUSION: Demineralization was observed in more than 2/3 of our PsA patients without axial involvement. This demineralization was not related to the indices of inflammation or disease duration, but there is a delayed correlation with HAQ score, as well as age and the number of years since menopause. PMID- 11196517 TI - Clinical and radiological amelioration of refractory peripheral spondyloarthritis by pulse intravenous pamidronate therapy. AB - OBJECTIVE: To examine the potential therapeutic properties of an aminobisphosphonate, pamidronate, using clinical and laboratory outcome variables together with dynamic magnetic resonance imaging (MRI) and gadolinium augmentation in patients with spondyloarthropathy (SpA) refractory to nonsteroidal antiinflammatory drugs (NSAID). METHODS: We studied 9 patients (7 male, 2 female) of mean age 27.9 years (range 19-38) and mean disease duration of 5.5 years (range 0.5-20). Five had ankylosing spondylitis (AS), 3 had undifferentiated SpA, and one had reactive arthritis. Seven were HLA-B27 positive. Two had inflammatory bowel disease. Pamidronate (60 mg) was given intravenously on Days 1, 2, 14, 28, and 56, over 4 h in 500 ml of 5% dextrose. Clinical outcome assessments included the BASDAI (disease activity), BASFI (function), BASGI (global well being) composite visual analog instruments, and swollen and tender joint count. Laboratory variables included the erthrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Dynamic MRI with gadolinium augmentation of synovium and bone was performed at baseline and at Day 84 in the first 6 patients enrolled in the study. RESULTS: All patients completed the study and there was a significant improvement in all clinical and laboratory variables assessed. Mean swollen and tender joint count decreased by 93.8% (p = 0.017) and 98.2% (p = 0.012), respectively, and complete clinical resolution of synovitis was noted in 5 patients. BASDAI decreased by 44.2% (p = 0.028), BASFI by 47.3% (p = 0.015), and BASGI by 42.2% (p = 0.011). ESR and CRP declined by 49.4% (p = 0.012) and 66.9% (p = 0.008), respectively. Acute lymphopenia accompanied by elevated CRP levels was noted in 8 patients in the 48 h after first pamidronate infusion. Maximal rate and magnitude of enhanced MRI signal after gadolinium augmentation decreased after pamidronate therapy, especially in the bone marrow. CONCLUSION: Preliminary data from uncontrolled studies support the efficacy of pamidronate therapy for NSAID refractory SpA and warrant further evaluation in controlled trials. PMID- 11196518 TI - Physical therapy is effective for patients with osteoarthritis of the knee: a randomized controlled clinical trial. AB - OBJECTIVE: To assess the effectiveness of physical therapy, given either as an individually attended treatment or in a small group format, in terms of pain, physical function, and health related quality of life for patients with osteoarthritis (OA) of the knee. METHODS: After 2 baseline assessments, 126 patients were randomized into one of 3 allocation arms: individual treatments (n = 43), small group format program (n = 40), and waiting list control (n = 43). After reassessment at 8 weeks, patients allocated to waiting list control were randomized into one of the 2 active treatment arms. Assessments included both self-report measures (WOMAC, SF-36) and objective measures of physical performance (gait analysis and muscle strength). RESULTS: Both physical therapy treatment allocations resulted in significant improvements in pain, physical function, and health related quality of life above the control group (standardized response mean 0.36 to 0.65). Improvements in the self-report measures were substantiated by significant correlated improvements in knee extensor strength and fast walking speed (rho 0.36-0.42). There were no significant differences in effectiveness between the 2 physical therapy allocations for any of the measured outcomes. Improvements gained were maintained for at least 2 months. Responsiveness to treatment was modified by loss of medial joint space width, the interaction being significant for physical function, gait, and knee extensor strength. CONCLUSION: Physical therapy, either as an individually delivered treatment or in a small group format, is an effective intervention for patients with knee OA. Responsiveness to this 8 week intervention was modified by loss of medial joint space width. PMID- 11196519 TI - Improvements following short term home based physical therapy are maintained at one year in people with moderate to severe rheumatoid arthritis. AB - OBJECTIVE: We previously demonstrated the efficacy of a 6 week home based physical therapy (PT) intervention for people with moderate to severe rheumatoid arthritis (RA). This followup study determined if short term improvements were maintained to one year. METHODS: Participants in the short term study were randomly assigned to receive a PT intervention (education, exercise, and pain relief modalities) delivered by physiotherapists with advanced rheumatology training (Weeks 0 to 6) or to a wait list control group. The control group received the intervention between Weeks 6 to 12. Outcome measures included the Stanford Arthritis Self-Efficacy Scale (SES), the Arthritis Community Research and Evaluation Unit Rheumatoid Arthritis Knowledge Questionnaire (KQ), and a visual analog scale for pain. Disease activity measures (tender joints, grip strength, and morning stiffness) were also included. MANOVA was used to compare within-subject scores at baseline and at 12 and 52 weeks. Paired t tests were used to determine if 12 week changes were maintained at 52 weeks. RESULTS: Of the 127 protocol completers, 117 (92.1%) were available for the one year followup. For those measures that showed significant improvement in the randomized controlled trial (SES, KQ, morning stiffness), improvements at 12 weeks were maintained at 52 weeks (p > 0.010). CONCLUSION: Subjects who participated in a short term home based PT intervention delivered by specially trained therapists reported improved outcomes following treatment, and these improvements were maintained at one year followup. Future studies need to explore the relative contributions of education, exercise, home based care, therapist training, and reinforcement strategies in improving longterm outcomes in RA. PMID- 11196520 TI - Comparative study of osteoarthritis of the contralateral knee joint of male amputees who do and do not play volleyball. AB - OBJECTIVE: To assess the prevalence of osteoarthritis (OA) of the contralateral knee of men with traumatic amputation who do and do not participate in regular, vigorous physical activity. METHODS: Three groups of patients were assessed. Group 1 consisted of 8 male amputee volleyball players. Group 2 consisted of 24 male amputees who do not play volleyball, and Group 3 was made up of 24 healthy controls matched by age and weight to Group 2. The prevalence of contralateral knee OA in Groups 1 and 2 was assessed by questionnaire, physical examination, and radiographs, and was compared with findings for Group 3. RESULTS: The rate of OA in all amputees (Groups 1 and 2 together) was 65.6%, which was significantly higher than among the controls (p < 0.05). The most common findings among the amputees were patellar and medial osteophytosis of the tibiofemoral joint, with a tendency to medial narrowing of the tibiofemoral joint space. CONCLUSION: Traumatic amputees have a higher prevalence of OA in the knee of the nonamputated leg than matched healthy controls. PMID- 11196521 TI - Chondroitin sulfate in osteoarthritis of the knee: a prospective, double blind, placebo controlled multicenter clinical study. AB - OBJECTIVE: To assess the efficacy and safety of chondroitin sulfate (CS) 1 g/day per os compared to placebo, in a double blind, randomized, parallel group study, with 3 months treatment followed by a 3 month posttreatment period, in patients with femorotibial osteoarthritis (OA). METHODS: The main criterion was the functional handicap assessed by Lequesne's algofunctional index (AFI). Secondary efficacy criteria were: self-assessed pain with activity and at rest, self assessed impact of OA on daily living, patient and physician assessed overall change in patient state since the previous visit, and daily NSAID and analgesic consumption, all evaluated monthly. The main analysis was performed on the intent to-treat (ITT) population at treatment endpoint compared to baseline (Day 0). RESULTS: The ITT efficacy data set comprised 130 patients (63 in CS group and 67 in placebo group). At treatment endpoint, the AFI showed greater but nonsignificant improvement in the CS than in the placebo group. Improvement became significant (p = 0.02) in the completer population (n = 114). In the ITT population, all variables tended towards greater improvement in the CS than the placebo group. In the completer population, pain at rest also significantly decreased in the CS group compared to the placebo group (p = 0.03), and, one month after treatment, CS had a significantly higher persistent effect than placebo on the AFI (p = 0.01), pain with activity (p = 0.001), physician assessed patient state (p = 0.05), and most other efficacy criteria. Adverse event rates did not differ significantly. CONCLUSION: We observed a trend towards efficacy of CS 1 g/day compared to placebo with good tolerability after 3 month treatment, and persistent efficacy one month posttreatment. Further investigations are required to confirm this trend. PMID- 11196522 TI - Single and multiple dose pharmacokinetics of acetaminophen (paracetamol) in polymedicated very old patients with rheumatic pain. AB - OBJECTIVE: To determine whether multiple dosing of acetaminophen would result in drug accumulation in polymedicated elderly patients with rheumatic pain. METHODS: Twelve inpatients (11 women), aged 89 +/- 4 years, weight 59 +/- 10 kg, receiving 3 to 8 concomitant medications, entered the study. Their creatinine clearance according to the Cockroft-Gault formula was 42 +/- 12 ml/min. The pharmacokinetics of 1 g acetaminophen was evaluated after the first dose (D1) and after the last dose (D7) during a 3 times daily regimen of 1 g for 5 consecutive days. RESULTS: The plasma pharmacokinetic profile of acetaminophen did not change significantly at D7 compared to D1. No significant within-patient differences were observed, especially with respect to plasma elimination half-life (2.74 +/- 0.48 and 2.77 +/- 0.32 hours, respectively), area under the concentration-time curve (82.5 +/- 21.1 and 90.1 +/- 15.2 microg x h/ml, respectively), and apparent oral clearance (3.68 +/- 0.85 and 3.28 +/- 0.52 ml/min/kg, respectively). CONCLUSION: No drug accumulation occurred during multiple dosing with acetaminophen in these very old subjects. On the basis of pharmacokinetic data alone, a dose regimen of acetaminophen 1 g tid seems to be appropriate in such patients. PMID- 11196523 TI - Surfing the Net--information on the World Wide Web for persons with arthritis: patient empowerment or patient deceit? AB - OBJECTIVE: In the past few years access to the Internet has become readily available. Patients are increasingly seeking and obtaining health information through the Internet, most often the World Wide Web (WWW). We assessed the content, authorship, and scope of the information available on WWW in relation to rheumatoid arthritis. METHODS: In an attempt to replicate use by the average person, a broad search of the Internet was conducted for the phrase "rheumatoid arthritis" using WebCrawler, a commonly used search engine. All the "hits" were critically assessed after visiting and collecting information from the respective Web sites in relation to relevance, scope, authorship, type of publication, and financial objectives. RESULTS: The search returned 537 hits. We evaluated 531-2 did not exist, 2 could not be contacted, one was not in English, and one required a membership to access. The 531 hits originated from 388 Web sites. Only 198 (51%) were considered to be relevant and 7 (2%) were of doubtful relevance. Thirty-four (17%) were posted by an individual, 57 (28%) by a nonprofit organization, 104 (51%) by a profit industry, and 10 (5%) by universities. Ninety one (44%) promoted alternative therapies, the most common including cetyl myristoleate, colloidal minerals, Pycnogenol, shark cartilage, and Tahitian Noni. Of the 107 sites with financial interests, 76 (71%) promoted alternative medicine. The first 100 hits only identified about a third of the nonprofit organizations or university owned Web pages. CONCLUSION: Many sites easily accessed by consumers appear to be profit based companies advertising an alternative product claimed to be effective for many conditions. These findings emphasize the need for critical evaluation of Web site contents. PMID- 11196524 TI - The arthritis of inflammatory childhood myositis syndromes. AB - OBJECTIVE: Arthritis has been an associated finding in juvenile dermatomyositis (JDM), but its prevalence, course, and response to therapy has not been well described. We investigated the frequency, course, and clinical and radiographic features in a large cohort of patients with JDM. METHODS: The charts of 94 patients with idiopathic myositis (1984-99) were reviewed: 80 JDM, 3 juvenile polymyositis (JPM), 5 amyopathic JDM, and 6 overlap myositis syndromes. Compiled data included demographics, clinical features, a detailed description of the arthritis, investigations (radiographs, autoantibodies), course, and response to therapy. All radiographs were independently reviewed by a single radiologist. RESULTS: Sixty-one percent (95% CI 50-72%) of patients with JDM had arthritis. The arthritis was reported a median 4.5 mo (range -73.6 to 76.6 mo) after the JDM onset. When compared to patients with no arthritis, the occurrence of arthritis was not significantly related to sex, race, positive antinuclear antibody or rheumatoid factor, calcinosis, nodules, vasculitis, or Raynaud's phenomenon. The initial involvement was pauciarticular in 67% and polyarticular in 33%. In the pauci group, asymptomatic knee effusions were the predominant finding (n = 19, 58%), and in 18 patients may have been the result of steroid therapy. Two patients evolved from a pauci onset to a polyarticular course. All responded to therapy (corticosteroids; 47 were taking other medications) with remission of the arthritis within a median of 2.0 mo (range 0.1-64.5 mo). However, the arthritis recurred in 39% as the corticosteroids were tapered. Four patients with JDM eventually required corticosteroid wrist injections, with resolution of the arthritis. The arthritis was nonerosive in all cases. No patient with JPM had arthritis. Three of 5 patients with amyopathic JDM and 4 of 6 with overlap myositis syndrome had a nonerosive polyarthritis. CONCLUSION: Nonerosive arthritis involving the knees, wrists, elbows, and fingers is a frequent manifestation of JDM and other idiopathic childhood myositis. The arthritis is seen early in the course of JDM and often responds to treatment. However, the arthritis may recur with tapering of corticosteroids despite remission of the JDM. In a significant proportion of JDM cases, arthritis is the major sequela and may warrant further medical therapy or intraarticular corticosteroid injections. PMID- 11196525 TI - Evidence for immune activation against oxidized lipoproteins in inactive phases of juvenile chronic arthritis. AB - OBJECTIVE: Oxidative stress contributes to joint inflammation and damage in rheumatoid arthritis. In a mobile inflamed joint, exercise induced multiple cycles of hypoxia-reperfusion injury may lead to the creation of a redox environment in which oxido-reductase systems, by NADPH mechanisms, produce highly reactive chemical species (i.e., oxygen free radicals). We investigated 2 endproducts of lipid peroxidation, malonildialdehyde (MDA) and diene conjugates (DC), and the formation of antibodies against oxidized low density lipoproteins (Ab oxLDL) in juvenile chronic arthritis (JCA), and assessed the role of oxidative phenomena in different phases and subsets of this disease. METHODS: To assess the role of oxidative stress in JCA, we measured the endproducts of lipid peroxidation, MDA and DC, by the increase of absorbance at 586 nm and 234 nm, respectively, and the levels of Ab oxLDL by ELISA in the sera of 58 patients with JCA and 21 healthy controls. Due to crossreactivity between Ab oxLDL and anticardiolipin antibodies (aCL), the sera were also tested by a standard ELISA for IgG-aCL. The patients were divided into 3 subsets: 29 with pauciarticular (pauci), 15 with polyarticular (poly), and 14 with systemic (sys) onset disease, and then were subdivided, according to different variables appropriate to each subset, reflecting active and inactive disease, into 30 active (14 pauci, 8 poly, 8 sys) and 28 inactive (15 pauci, 7 poly, 6 sys). RESULTS: Levels of Ab oxLDL were significantly increased in the whole group of patients (566.6 +/- 263.0 vs 206.6 +/- 136.3 mU/ml; p < 0.001) and in each of the type of onset (pauci 660.8 +/- 272.1, p < 0.001; poly 341.3 +/- 134.7, p < 0.01; sys 497.8 +/- 114.8, p < 0.001) compared to controls. Ab oxLDL were higher in the inactive than in the active group (743.5 +/- 231.9 and 404.4 +/- 169.9; p < 0.001). MDA and DC levels were not increased significantly in patients' sera. No patient was positive for IgG-aCL. CONCLUSION: These findings suggest that MDA and DC cannot be considered major markers of oxidative stress in JCA and that the Ab oxLDL may represent a delayed sign of oxidative stress previously induced by the inflammatory process in patients with JCA. PMID- 11196526 TI - Isolated tuberculous monoarthritis mimicking oligoarticular juvenile rheumatoid arthritis. AB - Isolated monoarthritis caused by Mycobacterium tuberculosis in the absence of clinical pulmonary disease is extremely rare in North America. After decades of consistent declines in incidence, a remarkable resurgence of tuberculosis (TB) is occurring in North America. It must always be considered in the differential diagnosis of chronic monoarthritis if devastating sequelae are to be avoided. We describe 2 cases of tuberculous arthritis in young children presenting with monoarthritis of the knee. The presumptive diagnosis in each case was oligoarticular onset juvenile rheumatoid arthritis (JRA). Each had an atypical course for JRA, with lack of response to intraarticular corticosteroid. The diagnosis of TB arthritis was made only with synovial biopsy. PMID- 11196527 TI - Central nervous system vasculitis as a complication of refractory dermatomyositis. AB - We describe a 47-year-old woman with refractory dermatomyositis (DM) who developed progressive cognitive dysfunction. Magnetic resonance imaging showed a large cerebral infarction, and the diagnosis of central nervous system (CNS) vasculitis was confirmed by both angiogram and brain biopsy. Her DM and CNS vasculitis responded promptly to the institution of daily cyclophosphamide, and her previously refractory disease entered remission. PMID- 11196528 TI - Self-injection of gold and methotrexate. PMID- 11196529 TI - Radiographic diagnosis of sacroiliitis--are sacroiliac views really better? PMID- 11196530 TI - Disappointing longterm result with disease modifying antirheumatic drugs. PMID- 11196531 TI - Nocardia pleural empyema complicating anti-Jo1 positive polymyositis during immunoglobulin and steroid therapy. PMID- 11196532 TI - Hemodynamics in vasculitides. PMID- 11196533 TI - Multifocal Staphylococcus aureus infection originating from the sacroiliac joint in a patient with rheumatoid arthritis. PMID- 11196534 TI - Stromelysin-1 (MMP-3) in synovial fluid of patients with rheumatoid arthritis has potential to cleave membrane bound Fas ligand. AB - OBJECTIVE: To investigate the relationship between matrix metalloproteinases (MMP) and the soluble form of Fas ligand (sFasL) in the synovial fluid (SF) of patients with rheumatoid arthritis (RA), and to determine which MMP have a major role in cleaving FasL. METHODS: The concentrations of sFas and sFasL in SF from 48 patients with RA and 43 patients with osteoarthritis (OA) were measured using specific ELISA. The levels of different MMP (MMP-1, 2, 3, 7, 9) in SF were also measured by ELISA. The active forms of gelatinases were detected by gelatin zymogram. Human FasL-expressing transfected cells (hFasL/L5178Y) were used to investigate whether FasL is cleaved from membrane bound FasL. RESULTS: Significantly higher levels of MMP-1, 3, and 9 were found in SF from RA patients compared to OA patients, but MMP-7 was not detectable in either group. The concentrations of sFas and sFasL in SF were also higher in RA than in OA patients. However, there was no relationship between the concentration of sFas and sFasL. Among MMP, MMP-3 concentrations in SF were closely correlated with the level of sFasL and with disease activity of RA. Enzymatic cleavage assay indicated that MMP-3 has potential to cleave the FasL expressed on hFasL/L5178Y cells and to produce sFasL. CONCLUSION: There was significant correlation between the concentration of sFasL and MMP-3 in SF of patients with RA. In addition, our data indicate that the shedding of FasL may be regulated by MMP-3 in the joint of patients with RA. PMID- 11196535 TI - Systemic onset juvenile idiopathic arthritis: a retrospective study of 80 consecutive patients followed for 10 years. PMID- 11196536 TI - Autoantibodies to CTLA-4 enhance T cell proliferation. PMID- 11196537 TI - Adverse reactions to rifabutin. PMID- 11196538 TI - Association between insulin-like growth factor status and physical activity levels in rheumatoid arthritis. AB - OBJECTIVE: To determine if the altered insulin-like growth factor (IGF) status in rheumatoid arthritis (RA) is due to inflammation, altered body composition, or lack of exercise. METHODS: Subjects included 73 patients with RA, 54 patients with other rheumatic diseases, both inflammatory and noninflammatory, and 28 healthy, physically active controls. Serum levels of IGF-I, IGF-II, and IGF binding protein-3 (IGFBP-3) were measured by radioimmunoassay. Body composition was estimated by bioelectrical impedance analysis, and habitual exercise level approximated by questionnaire. Statistical analysis was performed by 2 and 3 way ANOVA and moderated hierarchical regression. RESULTS: Serum IGF-I (p < 0.001), IGFBP-3 (p < 0.001), and the BP-3:total IGF molar ratio (p < 0.001) were depressed in both patient groups relative to controls. In contrast, IGF-II levels were depressed only in patients with RA (p < 0.01). Differences in the IGF proteins between patients and controls could not be attributed to inflammation. Habitual exercise level, but not body composition, was shown to be a significant predictor for IGF-I, IGFBP-3, and BP-3:total IGF molar ratio (p < 0.001). CONCLUSION: Our results indicate that the reduction in circulating IGF proteins observed in our patients is more related to their sedentary lifestyle than to the inflammatory process. This conclusion is in agreement with reports that show that highly active individuals typically exhibit higher levels of systemic IGF proteins than age matched sedentary controls. PMID- 11196539 TI - Genetic studies of psoriatic arthritis: dissecting joints and skin. PMID- 11196540 TI - Magnetic resonance imaging: a valuable method for the detection of synovial inflammation in rheumatoid arthritis. AB - OBJECTIVE: Clinical assessment of rheumatoid arthritis (RA) based on pain and swelling and physical examination is limited by observer error and interpretation. We compared magnetic resonance imaging (MRI) and clinical examination to detect synovitis in RA. METHODS: Twelve patients with active RA were assessed according to Ritchie index, swollen joint count and score, swollen joint count of hands and wrists [2 wrists, 10 metacarpophalangeal (MCP), 10 proximal interphalangeal (PIP)], morning stiffness, pain intensity, Disease Activity Score (DAS), erythrocyte sedimentation rate, and C-reactive protein. MR images of hands and wrists were obtained with an adapted device, on T1 weighted (T1W) spin echo (SE) coronal images before and after gadolinium DTPA, TIW SE axial images with gadolinium DTPA, T2* gradient echo recall coronal and axial sequences, and assessed by 2 radiologists (O = no synovitis, 1 = synovitis). RESULTS: The swollen joint count on hands and wrists was 59 on clinical examination (mean 5.08 +/- 3.15 per patient; 20/24 wrists, 7/120 MCP, 32/120 PIP) and 162 on MRI (mean 13.50+/- 5.65; 22/24 wrists, 70/120 MCP, 70/120 PIP). Statistically significant correlations were found between MRI synovitis count and swollen joint count (p = 0.015) and score (p = 0.019), Ritchie Index (p = 0.035), DAS (p = 0.02) and morning stiffness (p = 0.07). MRI revealed synovitis significantly more often than clinical examination (162 vs 59; p = 0.00002) [2 fold in PIP (70/32) and 10-fold in MCP (70/7)]. Clinical examination and MRI were concordant for 157/264 joints (59.5%). The association of normal MRI with synovitis on clinical examination was observed in 2 cases, the opposite in 105. CONCLUSION: MRI is more sensitive than clinical examination to detect synovitis of hands and wrists in RA, especially for MCP and PIP joints, and is valuable for assessment of inflammation in hands and wrists in RA. PMID- 11196541 TI - Plasma monocyte chemoattractant protein 1 is a marker for joint inflammation in rheumatoid arthritis. AB - OBJECTIVE: Monocyte chemoattractant protein 1 (MCP-1) level in plasma is described as a marker for joint inflammation in rheumatoid arthritis (RA). METHODS: MCP-1 in plasma and synovial fluid (SF) was quantified by ELISA in 36 RA patients with synovitis of the knee at Day 1 and 30. Disease activity was assessed by the swollen joint count, Ritchie Articular Index (RAI), global assessment, pain on visual analog scale, Health Assessment Questionnaire, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). RESULTS: By linear regression analysis plasma MCP-1 levels correlated significantly with the swollen joint count (Day 1: R = 0.47, p = 0.005; Day 30: R = 0.53, p < 0.001) and the RAI (Day 1: R = 0.37, p = 0.03; Day 30: R = 0.41, p = 0.01). The correlations of swollen joint count and RAI with ESR and CRP were significant only on Day 30 for the ESR (R = 0.40, p = 0.02). No association was found between plasma MCP-1 levels and the ESR/CRP levels. MCP-1 levels in plasma in RA patients were elevated compared to controls (p < 0.001) and MCP-I levels in SF were higher than in plasma (p < 0.001). No correlation was found between SF MCP-1 levels and in vitro migration of mononuclear cells towards SF. MCP-1 appears to participate in the disease process in RA, and plasma MCP-1 may be useful in monitoring joint inflammation. PMID- 11196542 TI - Epstein-Barr virus, methotrexate, and lymphoma in patients with rheumatoid arthritis and primary Sjogren's syndrome: case series. AB - OBJECTIVE: Rheumatoid arthritis (RA) and primary Sjogren's syndrome (SS) are associated with an increased risk of lymphoma. Epstein-Barr virus (EBV), a ubiquitous herpes virus, has been linked etiologically to lymphoma in patients with RA and primary SS. Recently, methotrexate (MTX) has also been linked to the development of these lymphomas. We investigated the frequency of EBV in lymphoma tissue of patients with RA and primary SS and the association of MTX with lymphomagenesis. METHODS: Twenty-three patients with RA and 9 with primary SS with a history of lymphoma were identified by writing to all Arthritis Foundation member rheumatologists in Washington State. Formalin fixed, paraffin embedded tissue blocks were then requested from pathology laboratories. Lymph nodes from 5 RA patients without lymphoma were also studied. In situ hybridization using a biotinylated EBER-1 oligonucleotide probe was used to detect EBV in tissue sections. Positive and negative laboratory controls were used to ensure procedural integrity. RESULTS: Specimens from 21 RA patients were obtained, with 2 subsequently excluded due to specimen quality. Specimens from 6 patients with primary SS were obtained. In situ hybridization for EBV was positive in 5/19 (26%) RA patients and 1/6 patients with primary SS. In the nonmalignant lymph nodes no patient showed EBV. One primary SS and 12 RA patients were known to be taking MTX at the time of lymphoma diagnosis. Of the EBV positive RA lymphoma patients, 4/5 were receiving MTX at the time of diagnosis. These results show that EBV is present in lymphoma tissue of some patients with RA and very few with primary SS. CONCLUSION: EBV is over-represented in the lymphomas of patients with RA, but whether MTX plays a role in predisposing patients with RA and primary SS to the development of lymphoma, perhaps by influencing behavior of EBV, remains unclear. PMID- 11196543 TI - Becoming a disability pensioner with rheumatoid arthritis in Norway 1971-1990. AB - OBJECTIVE: Physically demanding occupations have been associated with becoming a disability pensioner with rheumatoid arthritis (DPRA), but not with the disease of RA. The association with becoming DPRA probably reflects that patients with RA have difficulties in maintaining employment in a physically demanding occupation. However, the attitudes of the employers concerning employment of persons with RA might vary. For example, the patient's age may influence the strength of the association between a physically demanding occupation and becoming DPRA. We assessed whether the association between the predictors and becoming DPRA was stronger for the youngest or the oldest age group. METHODS: The study was prospective with data on persons in Norway 30-56 years old either in the census of 1970 or 1980. All new cases of DPRA during the 2 followup periods 1971-80 and 1981-90 were identified and analyzed by logistic regression. RESULTS: For women the predictors employment, low level of education, and period ( 1981-90 compared to 1971-80) were more strongly associated with becoming DPRA for the youngest compared to the oldest persons, while manual work and part time work were not predictors of becoming DPRA. For men, all the predictors in the study were more strongly associated with becoming DPRA for the youngest compared to the oldest age group. CONCLUSION: The higher risk of becoming DPRA was associated with most predictors for persons aged 30-39 years than the group aged 50-56 years. Our results appear to indicate that the consequences of having RA in the labor market are greater for the youngest age group. PMID- 11196544 TI - Opioid therapy for osteoarthritis of the hip and knee: use it or lose it? PMID- 11196545 TI - Carpal tunnel sonography by the rheumatologist versus nerve conduction study by the neurologist. AB - OBJECTIVE: To determine the value of sonography (SG) performed by the rheumatologist to diagnose carpal tunnel syndrome (CTS). METHODS: Sixty-three patients with clinical signs of CTS according to the neurologist, based on patient history and clinical examination, were studied. In the 6 weeks prior to surgery, SG was performed by a rheumatologist and nerve conduction study (NCS) was assessed. Improvement of initial complaints of 90% or more 3 months after surgery was considered to be the post-hoc gold standard for the diagnosis of CTS. RESULTS: After surgery, 47 patients (75%) experienced > or = 90% relief of complaints. Mean cross sectional area of the median nerve for patients with CTS was 11.3 mm2 compared to 6.1 mm2 in the control group. The sensitivity to detect CTS was 0.70 for SG and 0.98 for NCS, and specificity was 0.63 for SG and 0.19 for NCS. Positive predictive value was 0.85 for SG and 0.78 for NCS; negative predictive value was 0.42 for SG and 0.75 for NCS. Accuracy was 0.68 for SG and 0.78 for NCS. CONCLUSION: CTS can be identified by SG less sensitively but more specifically than by NCS. PMID- 11196546 TI - Incidence of elbow involvement in rheumatoid arthritis. A 15 year endpoint study. AB - OBJECTIVE: To evaluate the incidence of involvement and cause of destruction of humeroulnar (HU) and humeroradial (HR) joints in a prospectively followed cohort of 74 patients with seropositive and erosive rheumatoid arthritis (RA). METHODS: At the 15 year followup standard anteroposterior and lateral radiographs of 148 elbow joints were evaluated, and the grade of destruction was assessed by the Larsen method. RESULTS: Erosive involvement (Larsen grade 2) was observed in 75/148 (51%) elbows in 45/74 (61%) patients; 30 patients had bilateral and 15 unilateral involvement. The incidence of mild erosions (Larsen grade 2) was 49/148 (33%), and severe erosions (Larsen 3-5) 26/148 (18%). The 13 most severely involved (Larsen grade 4-5) joints were seen in 8 (11%) patients. Erosions were most often observed on the capitellum (64 joints) and the lateral epicondyle (58 joints) of the humerus (AP view) or on the olecranon of the ulna (52 joints). The Larsen score (0-100) for peripheral joints correlated significantly with the elbow joint Larsen grade on both sides: right, r = 0.53 (95% CI 0.34 to 0.68); left, r = 0.53 (95% CI 0.34 to 0.68). CONCLUSION: After 15 years more than half of the elbows and almost 2 of 3 patients with RA showed definite involvement of the elbow joint. Erosions were most often located on the capitellum and the lateral epicondyle of the humerus or the olecranon of the ulna. Severe destruction was most often bilateral. PMID- 11196547 TI - Analysis of leukemia inhibitory factor, type 1 and type 2 cytokine production in patients with eosinophilic fasciitis. AB - OBJECTIVE: Eosinophilic fasciitis (EF) is a scleroderma-like disease of unknown etiology characterized by skin induration, elevated immune globulins, and peripheral eosinophilia. The hallmarks of the chronic cutaneous involvement in this syndrome are inflammation and fibrosis of the fascia. To determine how the inflammatory process in EF may be regulated, we investigated the spontaneous and mitogen induced [lipopolysaccharide (LPS), phytohemagglutinin (PHA) or both LPS+PHA] syntheses of interleukins (IL)-2, 5 and 10, interferon-gamma (IFN gamma), and leukemia inhibitory factor (LIF) cytokines by peripheral blood mononuclear cells (PBMC) from 4 patients with active EF and compared them to those of 10 healthy individuals. METHODS: We used a short term whole blood assay and culture supernatants were collected after 24 h to measure the IL-2 and IFN gamma contents and after 48 h to evaluate IL-5, IL-10, and LIF. Supernatant cytokine concentrations were determined by ELISA. RESULTS: All 4 patients had similar patterns of cytokine secretion. Cytokine production did not differ between patients and controls under basal conditions or when LPS was added to the cultures. In contrast, under PHA or LPS+PHA stimulation, significantly higher amounts of all 5 cytokines were detected in samples from patients compared to those from controls. CONCLUSION: Overall, our data suggest that EF is characterized by an increased capacity of PBMC to produce IL-5 and IL-10, possibly leading to eosinophilia and immune globulin overexpression. In this context, the simultaneous elevations of type 1 cytokines (IL-2 and IFN-gamma) and LIF production by the same cells may be an attempt by the immune system to limit the exacerbation of a type 2 dominant response. PMID- 11196548 TI - Detection of nucleosome particles in serum and plasma from patients with systemic lupus erythematosus using monoclonal antibody 4H7. AB - OBJECTIVE: To develop a monoclonal antibody reagent that would react with nucleosomes but not directly with constituent double stranded DNA (dsDNA) or with histones. METHODS: Mice were immunized with highly purified chicken mononucleosomes and hybridomas employed to produce Mab that did not react with dsDNA or histones but still showed reactivity with nucleosomes. RESULTS: Murine monoclonal IgG antibody 4H7, generated from a mouse immunized with highly purified chicken erythrocyte nucleosomes, showed no direct ELISA reactivity with either dsDNA or isolated histones or with Sm and RNP antigens or combinations of any of these components. Mab 4H7 did show strong ELISA reactivity for chicken erythrocyte and calf thymus nucleosomes as well as for human leukocyte nucleosomes. The Mab did show strong ELISA reactions with peptides 1-25 of histone H2B and 1-21 of H3, which correspond to sequences known to be located at the surface of nucleosomes. We then measured relative serum levels of 4H7 reactive nucleosome antigen in 140 patients with systemic lupus erythematosus (SLE) in parallel with 50 non-SLE patients with other types of connective tissue disease and 92 healthy subjects. Occasional low levels of serum nucleosomal antigen were seen in 4 of 92 controls, but many patients with SLE (66/140) showed marked elevations of serum nucleosomal antigen. No difference was observed when serum or plasma samples were studied. A marked correlation (R = 0.401, p < 0.0001) was noted when disease activity score (SLEDAI) was plotted against optical density value measured with 4H7 in ELISA. Further, the levels of circulating nucleosomes were raised in SLE patients with very active central nervous system and renal involvement. CONCLUSION: Presence of nucleosome related antigen in sera from patients with SLE may provide insight into the sequence of disease related antigenic stimuli in active SLE. PMID- 11196549 TI - Phase I clinical trial of a monoclonal antibody against CD40-ligand (IDEC-131) in patients with systemic lupus erythematosus. AB - OBJECTIVE: To investigate the safety and pharmacology of a humanized monoclonal antibody against CD40-ligand (IDEC-131) in patients with systemic lupus erythematosus (SLE). METHODS: Cohorts of 3 to 5 patients with symptomatic lupus each received 0.05, 0.25, 1.0, 5.0, or 15.0 mg/kg of IDEC-131 as a single intravenous infusion. Patients were followed for 3 months to evaluate toxicity and pharmacokinetics. RESULTS: This phase I, single dose, dose-escalating study was conducted in 23 patients at a single institution. All patients experienced at least 1 adverse event (AE) during a 3 month followup period, although 58 AE in 17 patients were considered possibly or probably related or of unknown relationship to treatment. No dose relationship in the distribution of AE was apparent. No infusion related cytokine-release syndrome was observed; no infusions were interrupted, and all patients completed treatment. Eight mild (grade 1 or 2) infections were reported in 8 patients. All infections were considered unrelated to drug administration and all resolved uneventfully. No patient developed detectable antibodies to IDEC-131. Flow cytometry revealed no apparent treatment related depletion of lymphocyte subsets. Pharmacokinetic analysis indicated that the maximum serum concentration and the area under the concentration curve of IDEC-131 were proportional to the dose administered. At doses between 1.0 and 15.0 mg/kg, the serum half-life ranged from 299 to 320 h. Efficacy was not formally evaluated in this single dose study. CONCLUSION: IDEC-131 (humanized Mab against CD40L) administered in a single intravenous infusion at doses of 0.05 15.0 mg/kg is safe and well tolerated in patients with SLE. PMID- 11196550 TI - Localization of arrhythmogenic triggers of atrial fibrillation. AB - INTRODUCTION: Mapping procedures to identify triggers of atrial fibrillation from pulmonary veins (PVs) are not well established. We sought to determine the value of multipolar recordings from the coronary sinus (CS) and crista terminalis (CT) for identifying the origin of paced and atrial premature depolarizations (APDs) initiating atrial fibrillation from left versus right PVs. METHODS AND RESULTS: Fifteen patients with paroxysmal atrial fibrillation refractory to medications had decapolar catheters (5-mm electrode, 2-mm interelectrode spacing) placed in the CS and posterior medial to the CT. Bipolar electrograms were recorded at each site. Electroanatomic left atrial endocardial maps were created in sinus rhythm, and each PV was identified and paced. During spontaneous APDs initiating atrial fibrillation and PV pace maps, the atrial activation and the earliest electrogram at CS and CT were compared. PV sites were designated as sites of origin of APDs when (1) intracardiac electrograms in the CS and CT during arrhythmogenic APDs matched those of PV pace maps, (2) local activation preceded CS and CT recordings by at least 40 msec (all sites), and (3) atrial depolarizations were eliminated by application of radiofrequency energy (24/26 sites). Pacing from each of the 30 right PV sites resulted in proximal to distal CS activation and later recordings at the CS than the CT (earliest CS-CT activation range: -15 to -58 msec, mean -32 +/- 12). In contrast, pacing from the left PV sites typically (28/30 sites) activated the CS from the distal to proximal poles and demonstrated simultaneous or earlier (CS-CT range: -14 to +54 msec, mean 13 +/- 17) recordings of the CS than the CT (P < 0.0001). For 13 APDs mapped to the right PVs, CS minus CT activation was -17 to -49 msec (mean -31 +/- 8). For 13 APDs localized to the left PVs, the CS minus CT activation time ranged from -8 to +28 msec (mean 14 +/- 15). CONCLUSION: Activation sequence mapping from multipolar catheters placed in the CS and along the posterior medial CT rapidly differentiates right and left PV sites of origin of atrial depolarization. PMID- 11196551 TI - How to find the fibrillating site? Brain exercise versus fancy mapping tools. PMID- 11196552 TI - Importance of the atrial channel for ventricular arrhythmia therapy in the dual chamber implantable cardioverter defibrillator. AB - INTRODUCTION: Performance of dual chamber implantable cardioverter defibrillator (ICD) systems has been judged based on functioning of the ventricular tachycardia:supraventricular tachycardia (VT:SVT) discrimination criteria and DDD pacing. The purpose of this study was to evaluate the use of dual chamber diagnostics to improve the electrical and antiarrhythmic therapy of ventricular arrhythmias. METHODS AND RESULTS: Information about atrial and ventricular rhythm in relation to ventricular arrhythmia occurrence and therapy was evaluated in 724 spontaneous arrhythmia episodes detected and treated by three types of dual chamber ICDs in 41 patients with structural heart disease. Device programming was based on clinically documented and induced ventricular arrhythmias. In ambulatory patients, sinus tachycardia preceded ventricular arrhythmias more often than in the hospital during exercise testing. The incidence of these VTs could be reduced by increasing the dose of a beta-blocking agent in only two patients. In five patients in whom sinus tachycardia developed after onset of hemodynamic stable VT, propranolol was more effective than Class III antiarrhythmics combined with another beta-blocking agent with regard to the incidence of VT and pace termination. In all but three cases, atrial arrhythmias were present for a longer time before the onset of ventricular arrhythmias. During atrial arrhythmias, fast ventricular rates before the onset of ventricular rate were observed more often than RR irregularities and short-long RR sequences. Dual chamber diagnostics allowed proper interpretation of detection and therapy outcome in patients with different types of ventricular arrhythmia. CONCLUSION: The advantages of the dual chamber ICD system go further than avoiding the shortcomings of the single chamber system. Information from the atrial chamber allows better device programming and individualization of drug therapy for ventricular arrhythmia. PMID- 11196553 TI - Effect of sodium channel blockers on ST segment, QRS duration, and corrected QT interval in patients with Brugada syndrome. AB - INTRODUCTION: Brugada syndrome is characterized by an ST segment elevation in leads V1-V3 and a high incidence of ventricular fibrillation (VF). A mutation in a cardiac Na+ channel gene, SCN5A, has been linked to Brugada syndrome, and sodium channel blockers have been shown to be effective in unmasking the syndrome when concealed. The aim of this study was to examine the effects of Na+ channel blockers on ST segment elevation, QRS, corrected QT (QTc) interval, and ventricular arrhythmias in patients with Brugada syndrome. METHODS AND RESULTS: We examined the effects of three different Na+ channel blockers (flecainide, disopyramide, and mexiletine) on the amplitude of the ST segment 20 msec after the end of QRS (ST20), QRS duration, QTc interval measured from 12-lead ECG, and ventricular arrhythmias in 12 Brugada and 10 control patients. Maximum ST20 observed in the V2 or V3 leads under baseline conditions was greater in the Brugada patients than in control patients, whereas QRS duration and maximum QTc interval were no different between the two groups. Flecainide and disopyramide, but not mexiletine, significantly increased maximum ST20 and QRS duration in both groups, although these effects were much more pronounced in the Brugada patients. The increases in ST20 and QRS duration with flecainide were significantly larger than those with disopyramide. An increase of 0.15 mV in ST20 with flecainide separated the two groups without overlap. Ventricular premature complexes developed only with flecainide in Brugada patients (3/12) displaying a marked ST elevation but not widening of QRS. CONCLUSION: Our findings suggest that Na+ channel blockers amplify existing I(Na) and possibly other ion channel defects, with a potency inversely proportional to the rate of dissociation of the drug from the Na+ channel, thus causing a prominent elevation of the ST segment and, in some cases, prolongation of QRS duration in patients with Brugada syndrome. PMID- 11196554 TI - ST segment elevation and sudden cardiac death: from the Brugada syndrome to acute myocardial ischemia. PMID- 11196555 TI - Continuous telemetry from a chronic canine model of sudden cardiac death. AB - INTRODUCTION: We sought to develop a continuously telemetered animal model of sudden cardiac death (SCD) to study the role of existing infarcts and acute ischemia in fatal arrhythmias. METHODS AND RESULTS: A telemetry system capable of recording eight channels of electrophysiologic data continuously and chronically has been developed. To demonstrate the use of this technology in an animal model of sudden death, 12 anesthetized dogs were instrumented with eight electrodes located in endocardium of the right side of the heart, epicardium of the left ventricle (LV), or in the subcutaneous tissues. The left anterior descending (LAD) coronary artery was occluded for 90 minutes and reperfused to produce LV infarction. A copper wire was placed in the left circumflex (LCX) coronary artery to cause intimal injury in a second arterial bed. The telemetry unit recorded deaths in seven animals between 19 to 64 hours after surgery. Five animals that did not experience SCD by the fifth postoperative day served as controls. There were three modes of SCD: complex ventricular ectopy that degenerated into ventricular fibrillation (VF, n = 4); normal sinus rhythm that suddenly degenerated into VF (n = 1); and bradycardia (RR intervals >1,000 msec) that lasted >3 minutes and preceded VF (n = 2). ST segment changes were significantly greater in the LCX-bed electrograms for tachyarrhythmic compared to bradyarrhythmic deaths (mean +/- SD; 4.0 +/- 3.4 mV and 0.2 +/- 0.8 mV, respectively). Fast Fourier transform showed the peak frequency of VF 10 seconds after onset was significantly higher in the five dogs with initial tachyarrhythmias compared with the VF that followed profound bradycardia (6.5 +/- 3.1 Hz and 3.7 +/- 0.6 Hz, respectively). Computer-assisted planimetry of postmortem heart slices revealed that infarcts in the two dogs with bradycardic events were larger (19.7% +/- 2.2% of the LV and septal mass) than in the five dogs with tachyarrhythmias (7.7% +/- 2.4%) or in the five control dogs (11.9% +/- 8.1%). CONCLUSION: It is possible to record via telemetry the events leading to SCD in an animal model. Continuous telemetry monitoring demonstrated that both tachyarrhythmias and bradyarrhythmias ultimately resulted in VF in an animal model of SCD. Animals with tachyarrhythmic deaths had greate ischemia in the LCX bed, smaller preexisting infarcts, and higher VF peak frequency than animals with bradyarrhythmic deaths. PMID- 11196556 TI - Long-term monitoring of animal models of sudden death. PMID- 11196557 TI - Colocalization of tenascin and sympathetic nerves in a canine model of nerve sprouting and sudden cardiac death. AB - INTRODUCTION: Sympathetic nerve sprouting after myocardial infarction (MI) may contribute significantly to the occurrence of ventricular arrhythmia and sudden cardiac death. Tenascin-X (TnX), a matrix protein known to be associated with nerve growth in central and peripheral nerves, also may play a role in cardiac nerve sprouting after MI. METHODS AND RESULTS: Immunocytochemical staining techniques were used to identify nerves in 5-microm serial sections from 6 normal dogs and 11 dogs with MI. Among the dogs with MI, 4 also received nerve growth factor infusion to the left stellate ganglion. The time between MI to tissue harvest averaged 35.7 +/- 14.4 days. Tyrosine hydroxylase (TH) stain was used to identify sympathetic nerves, and growth-associated protein-43 (GAP-43) was used to identify growing nerves. Polyclonal antibody was obtained for use in identifying TnX. Nerves were evident in both the infarcted and noninfarcted areas. Many nerves were found around blood vessels. A total of 181 nerves in 69 slides were examined: 89 were from noninfarcted myocardium, 4 from infarct, 13 from infarct border zone, and 75 from perivascular regions. Except in normal dogs, all nerves stained positive for TH also stained positive for GAP-43, indicating sympathetic nerve sprouting after MI. In all dogs, the nerves that stained positive for TH also stained positive for TnX. CONCLUSION: There is a colocalization of TnX, GAP-43, and TH in sprouted cardiac nerves. These results suggest that TnX is important not only in the existing normal myocardial nerve cells but also in cardiac sympathetic nerve sprouting after MI. PMID- 11196558 TI - Mechanisms of sympathetic neural regeneration after myocardial infarction: more questions than answers. PMID- 11196559 TI - Is all ventricular fibrillation the same? Influence of mode of induction on characteristics of ventricular fibrillation. AB - INTRODUCTION: Little information is available on the relationship between the mode of induction of ventricular fibrillation (VF) to VF characteristics. METHODS AND RESULTS: VF was induced from the anterior left ventricle by programmed electrical stimulation, burst pacing, alternating current (AC), high current S2 at a site remote from S1, T wave shock, and intersecting wavefronts in seven normal dogs and seven dogs with chronic myocardial infarction. Using two electrode arrays, 112 electrograms were recorded from the anterior and lateral wall. Cycle lengths were analyzed and activation vectors were created by summing orthogonally recorded bipolar electrograms. The magnitude of the vector loops was integrated over time to produce an "ensemble vector" index (EVI) whose magnitude is high when beat-to-beat activation direction is consistent and low when activation direction is variable. T wave shock-induced VF had a significantly longer cycle length 1 to 5 seconds after VF onset than other modes of induction (P < 0.05). The frequency-corrected EVI was significantly larger for AC current and T wave shock-induced VF as opposed to all other modes of VF induction in early VF (P < 0.0001). After 10 seconds of VF, these differences persisted only on the anterior wall. CONCLUSION: VF induced in animals by T wave shock and AC current had different characteristics than VF induced by other methods. These findings may have implications for our understanding of VF pathophysiology. PMID- 11196560 TI - Fibrillation is more complex in the left ventricle than in the right ventricle. AB - INTRODUCTION: The mechanisms that maintain ventricular fibrillation (VF) are not completely understood. It has been proposed that increased ventricular wall thickness destabilizes VF wavefronts and therefore is an important determinant of VF activation patterns. We hypothesized that if this is the case, then VF patterns on the thin-walled right ventricle (RV) should be simpler than those on the thick-walled left ventricle (LV). METHODS AND RESULTS: In seven open chest pigs, we mapped VF simultaneously from two epicardial recording arrays, one on the RV and one on the LV. Each array contained 504 unipolar electrodes (in a 21 x 24 grid) spaced by 2 mm. We used specialized pattern analysis methods to compute quantitative descriptors of RV and LV activation patterns. Our data show that VF is more organized in the RV than the LV, containing fewer, larger wavefronts that follow fewer distinct pathways and are less likely to fragment or collide with other wavefronts. The incidence, size, and cycle length of reentrant circuits were similar in the two ventricles, but RV reentry persisted for more cycles. These results are not predicted by the differences in electrophysiologic properties between LV and RV that have been reported in mammalian hearts. CONCLUSION: The geometry of the ventricular wall, particularly wall thickness, is an important determinant of VF activation patterns. PMID- 11196561 TI - Understanding ventricular fibrillation by quantifying the complexity of activation patterns. PMID- 11196562 TI - Profibrillatory effects of verapamil but not of digoxin in the goat model of atrial fibrillation. AB - INTRODUCTION: Verapamil and digoxin have been shown to modulate tachycardia induced atrial electrical remodeling. The goal of the present study was to determine the direct effects of verapamil and digoxin on atrial fibrillation (AF), before and after electrical remodeling. METHODS AND RESULTS: In six goats we measured the AF cycle length (AFCL) and duration of AF (DurAF) of 50 consecutive induced paroxysms, before (t = 0) and after 24 hours (t = 24) of electrical remodeling. During AF, conduction velocity (CV(AF)), refractory period (RP(AF)), and type of AF (I, II, III) were determined. Verapamil was administered at a loading dose of 0.1 mg/kg, followed by a continuous (2-hour) infusion of 5 microg/kg/min. Digoxin was given intravenously as a single 0.02 mg/kg bolus. At t = 0 and t = 24, digoxin and verapamil caused a significant slowing of the ventricular rate of >40%. Digoxin had no effect on DurAF, AFCL, CV(AF), or RP(AF). Infusion of verapamil had a direct proarrhythmic effect. Both at t = 0 and t = 24, AFCL and RP(AF) were shortened by about 15%. During acute AF, verapamil prolonged the average duration of AF paroxysms from 7 to 16 seconds. After 24 hours of AF, the proarrhythmic effect was much stronger. Shortly after starting infusion (6 +/- 2 min), verapamil converted paroxysmal AF into sustained AF. As long as verapamil infusion was maintained, AF no longer terminated in any of the goats. This effect was associated with an increase in AF fragmentation from type I to type II-III. CONCLUSION: Verapamil shortens AFCL and RP(AF) in the presence and absence of electrical remodeling. After 24 hours, it exerted a marked proarrhythmic effect and converted paroxysmal (type I) into sustained (type III) AF. In contrast, digoxin had no effect on the rate or stability of AF. PMID- 11196563 TI - Termination of spiral waves with biphasic shocks: role of virtual electrode polarization. AB - INTRODUCTION: This simulation study seeks to extend the virtual electrode polarization (VEP) theory for defibrillation to explain the success and failure of biphasic shocks. The goals of the study are to (1) provide insight into why optimal biphasic shocks have a lower voltage defibrillation threshold than monophasic shocks, (2) examine the mechanisms of biphasic shock failure and to determine whether they differ from those of monophasic shocks, and (3) study how the timing of biphasic shock delivery to a spiral wave affects voltage defibrillation threshold. METHODS AND RESULTS: A spiral wave is initiated in a bidomain representation of a 2-cm x 2-cm sheet of ventricular myocardium. The model incorporates nonuniform fiber curvature, membrane kinetics suitable for high-strength shocks, and electroporation. A spatially uniform extracellular field is delivered by line electrodes. The shock establishes VEP that dictates the postshock activity in the tissue. Our results demonstrate that the second phase of biphasic shocks leaves the tissue with substantially smaller postshock excitable gap, thus eliminating the majority of the substrate for reinitiation of reentrant activity. Further, the occurrence of break excitations for weaker biphasic shocks indicates that the mechanisms for biphasic shock failure are more complex than for monophasic shocks. Biphasic voltage defibrillation thresholds range from 8 to 16 V/cm, depending on the position of the spiral wave. An increase in the amount of preshock excitable gap leads to an increase in voltage defibrillation threshold. CONCLUSION: This study demonstrates the importance of VEP and its interaction with preshock activity in the success and failure of biphasic defibrillation shocks. PMID- 11196564 TI - Time course of left atrial mechanical recovery after linear lesions: normal sinus rhythm versus a chronic atrial fibrillation dog model. AB - INTRODUCTION: The extent of left atrial (LA) mechanical function recovery after creation of linear lesions using the loop catheter has not been determined. METHODS AND RESULTS: LA mechanical function was assessed before and after linear lesions using transthoracic two-dimensional and Doppler echocardiography in two groups: (1) normal, which consisted of eight healthy dogs in normal sinus rhythm (NSR); and (2) atrial fibrillation (AF), which consisted of nine dogs in spontaneous AF for 6 months following rapid pacing-induced AF. NSR was restored with linear lesions in all AF dogs. All animals were in NSR 5 months after linear lesions. In the normal dogs, the maximal velocity of the transmitral flow "A" wave was reduced by 42% during the first week postablation and by 24% at 5 months versus preablation. At 5 months, no differences in LA function were noted between the normal and the AF group for all measured Doppler parameters. At 5 months, the LA systolic area in AF dogs was reduced by 40% (preablation 12.9 +/- 2.9 cm2, postablation 7.6 +/- 1.2 cm2; P < 0.01) and in the normal dogs by 21% (preablation 10.0 +/- 0.9 cm2, postablation 7.8 +/- 1.2 cm2; P < 0.02), being the same in both groups within 3 months of recovery. CONCLUSION: The creation of linear lesions with the loop catheter does not result in LA expansion. In normal dogs, LA mechanical activity is reduced for 3 weeks postablation. The time course of LA mechanical function recovery is the same for the AF and the NSR dogs, and it is complete at 3 months postablation. At 5 months, LA systolic function parameters in both groups are reduced by 24% versus the preablation values of the normal dogs. Linear lesions result in a significant reduction in LA size. PMID- 11196565 TI - In atrial fibrillation, size does matter. PMID- 11196566 TI - Endocardial noncontact activation mapping of idiopathic left ventricular tachycardia. AB - Idiopathic left ventricular tachycardia with a right bundle, left-axis deviation is thought to originate from posterior fascicles. Recently, there has been considerable interest in the anatomic and mechanistic basis of this arrhythmia. We report our experience with a 26-year-old man in whom new noncontact mapping technology was used to acquire detailed data from the left ventricle, identify the mid-diastolic potential and part of the ventricular tachycardia circuit, and perform successful ablation. This information helped define the physiologic aspects of this unique tachycardia. PMID- 11196567 TI - Long QT syndrome: cellular basis and arrhythmia mechanism in LQT2. AB - LQT2 is one form of the congenital long QT syndrome. It results from mutations in the human ether-a-go-go-related gene (HERG), and more than 80 mutations, usually causing single amino acid substitutions in the HERG protein, are known. HERG encodes the ion channel pore-forming subunit protein for the rapidly activating delayed rectifier K+ channel (I(Kr)) in the heart. This review summarizes current findings about mutations causing LQT2, the mechanisms by which mutations may cause the clinical phenotype of a reduction in I(Kr) and a prolonged QT interval, and how this may be involved in the generation of ventricular arrhythmias. PMID- 11196568 TI - An electrocardiographic masquerade. AB - A 60-year-old woman underwent successful pulmonary embolectomy for a massive pulmonary embolism. On postoperative day 2, while receiving intravenous dopamine for hypotension, she developed the tachycardia, and a 12-lead ECG was obtained (Fig. 1). Figure 2 shows the 12-lead ECG obtained on the previous day, when she was in sinus rhythm with frequent premature PMID- 11196569 TI - Prolonged atrioventricular block during AAI pacing for sick sinus syndrome. PMID- 11196571 TI - Asymmetric photolysis with elliptically polarized light. AB - Previous investigations have shown the efficacy of right-(RCPL) and left-(LCPL) circularly polarized light in promoting the asymmetric photolysis of racemic organic substrates and producing measurable enantiomeric excesses (e.e.s) when photolysis is incomplete. Synchrotron radiation, polychromatic and having out-of plane components which are elliptically and ultimately circularly polarized, has been suggested as a universal source of RCPL and LCPL on a cosmic scale. The more prevalent right-(REPL) and left-(LEPL) elliptically polarized components have never been investigated for similar capabilities. The present study, using a 212.8 nm laser beam to mimic the synchtrotron radiation, explores the potential of REPL and LEPL in this context and finds a qualitative trend indicating that each induces asymmetric photolysis in the same sense as RCPL and LCPL, but to a lesser degree. PMID- 11196570 TI - Nonenzymatic template-directed condensation of short-chained oligouridylates on a poly(A) template. AB - An oligouridylate with chain-length of more than three was condensed on a polyadenylate [poly(A)] template with 1-ethyl-3-(3 dimethylaminopropyl)carbodiimide (EDAC) in imidazole buffer. The condensation reaction proceeds via the phosphorimidazolide of the oligouridylate as an intermediate. Pentauridylate [(pU)5] was converted to decauridylate [(pU)10] in 10% yield at 0 degree C for 7 days in the presence of the poly(A) template, while no coupling product was obtained in the absence of the poly(A) template. The resulting linkage of the (pU)10 was mainly 2'-5' linkage. PMID- 11196572 TI - Synthesizing oligomers from monomeric nucleotides in simulated hydrothermal environments. AB - Dimers and trimers of adenosine monophosphate (AMP) were synthesized from AMP in environments simulating hot vents on the sea floor of the primitive Earth. The simulated environments were made in the flow reactor, in which an aqueous solution of reactants was circulated from the hot to the cold region repeatedly. The oligomerization proceeded most significantly when the hot reaction solution at about 110 degrees C was abruptly ejected into the cold environment maintained at about 0 degree C. PMID- 11196573 TI - Hydrothermal circulation of seawater through hot vents and contribution of interface chemistry to prebiotic synthesis. AB - Synthesizing oligopeptides from glycine and alanine in a flow reactor, which stimulates constant hydrothermal circulation of seawater through hot vents on the primitive Earth, demonstrated that an exponential growth of the products is possible. The initial rapid growth of the product is a consequence of using the products formed in one cycle as the starting materials for the cycle of synthesis. PMID- 11196574 TI - Prebiotic methylation and the evolution of methyl transfer reactions in living cells. AB - An hypothesis is presented for the prebiotic origin of methyl groups and the evolution of methyl transfer reactions in living cells. This hypothesis, described in terms of prebiotic and early biotic chemical evolution, is based on experimental observations in our lab and in those of others, and on the mechanisms of enzymatic methyl transfer reactions that occur in living cells. Of particular interest is our demonstration of the reductive methylation of ethanolamine and glycine in aqueous solution by excess formaldehyde. These reactions, involving prebiotic compounds and conditions, are mechanistically analogous to the de novo origin of methyl groups in modern cells by reduction of methylene tetrahydrofolate. Furthermore, modern cellular methyl transfers from S adenosylmethionine to amine nitrogen may involve formaldehyde as an intermediate and subsequent reductive methylation, analogous to the prebiotic chemistry observed herein. PMID- 11196575 TI - Formation of peptide bonds from metastable versus crystalline phase: implications for the origin of life. AB - Formation of peptide bonds was attempted by thermal activation of dry amino acids from aqueous solution that simulated prebiotic evaporative environments. The evaporation trend of amino acids solutions shows a bifurcation and can lead to either a crystalline phase (near equilibrium) or a metastable non-crystalline phase (far from equilibrium). Only amino acids in this metastable phase are able to form peptide bonds by thermal activation at temperatures that are generated by solar radiation today. We suggest that this metastable phase is the ideal initial material to trigger amino acid assemblage with protein-like structure because provide the driving force (supersaturation) for an intense interaction between monomers of different amino acids and allows activation of these monomers in plausible prebiotic conditions. PMID- 11196576 TI - Abiotic synthesis of guanine with high-temperature plasma. AB - The origin of guanine has been unknown, though there are some reports concerning its abiotic synthesis. We show here that guanine, as well as uracil and cytosine, are synthesized from a 90%N2-10%CO-H2O gas mixture via a complex organic product produced with the high-temperature and rapid quenching technique. This result implies that a large amount of complex organic matter including precursors of bioorganic compounds might have been produced on the primitive earth after cometary impacts. PMID- 11196577 TI - Fine structure of fossilized bacteria in Volyn kerite. AB - Ultrathin sectioning and cryofracture of fibrous kerite, sampled from 1.8-1.75 billion year old Volyn sediments (Ukraine), revealed in bacteria-like bodies the presence of structures similar to sheath, cell wall, periplasm, cytoplasm, septum, membranes, intramembrane particles, poly-beta-hydroxybutyrate inclusions. On the strength of these data and also the fatty acid profiles of these microfossils, we concluded that fibrous kerites are biogenic formations, namely fossilized bacterial mats. PMID- 11196578 TI - [Intracellular calcium: physiology and physiopathology]. AB - Many important aspects of our life are regulated by the free cytosolic Ca2+ concentration. The intracellular Ca2+ signal is regulated both in space, frequency and amplitude. Each cell chooses a unique set of Ca2+ signals to control its function. Ca2+ signal transduction is based on rises in free cytosolic Ca2+ concentration. Ca2+ can come from the extracellular space or be released from intracellular stores. Extracellular Ca2+ enters the cell through various types of plasma-membrane Ca2+ channels and leaves the cell using Ca2+ pumps and Na+/Ca(2+)-exchangers. Ca2+ is accumulated in intracellular stores by means of Ca2+ pumps and is released via inositol 1,4,5-trisphosphate (IP3) and ryanodine receptors. Mutations or abnormalities in one of the above mentioned Ca(2+)-transporting proteins can lead to disease. Skeletal-muscle pathology can be caused by abnormal ryanodine receptors (malignant hyperthermia, porcine stress syndrome, central core disease), plasma-membrane Ca2+ channels (hypokalemic periodic paralysis, muscular dysgenesis mice, paraneoplastic Lambert-Eaton myasthenia syndrome) or Ca2+ pumps (Brody disease). Neurologic disorders can be related to altered function of plasma-membrane Ca2+ channels (episodic ataxia type 2, spinocerebellar ataxia type 6, familial hemiplegic migraine, glutamate excitotoxicity, tottering, leaner, lethargic and stargazer mice), IP3 receptors (Lowe's oculocerebrorenal syndrome, manic depression, Alzheimer's disease, opisthotonos mice) and Ca2+ pumps (deafwaddler mouse and wriggle mouse sagami). Two skin diseases are caused by Ca(2+)-pump mutations (Darier disease and Hailey Hailey disease). Incomplete X-linked congenital stationary night blindness is caused by a mutation in the plasma-membrane Ca2+ channels in rods and cones. PMID- 11196579 TI - [Intra- and intercellular Ca(2+)-signal transduction]. AB - Calcium is one of the most universal signal-transduction elements in a large variety of cells ranging from bacteria to specialized neurons. Ca2+ acts as a second messenger controlling such processes as secretion, cell differentiation or signal transmission. In order to be able to execute their specific functions and to react in a coordinated way to stimuli, multicellular organs need a precise orchestration of cellular functions. For this purpose cells have developed different forms of intercellular communication (IC). In this study we investigated a number of mechanisms of intracellular propagation and IC using experiments with fluorescent Ca(2+)-indicators, confocal microscopy and digital imaging techniques. In ROS 17/2.8 osteoblasts, retinal pigment epithelial cells (RPE) and CPAE endothelial cells, a small mechanical deformation of the plasma membrane results in a transient increase of free cytoplasmic Ca2+ concentration ([Ca2+]i). This Ca(2+)-rise starts at the site of stimulation and propagates concentrically to neighboring cell layers. The intracellular Ca(2+)-wave in RPE and ROS cells is caused by Ca(2+)-influx followed by Ca(2+)-release from the intracellular stores and by intercellular propagation of the Ca(2+)-wave. The [Ca2+]i-transient upon mechanical stimulation of LLC-PK1 epithelial cells, C6 glioma cells and MLO-Y4 osteocytes was limited and/or variable. In CPAE cells only the intracellular release is important for evoking the Ca(2+)-transient, and is followed by IC. IC can occur via gap junctions (GJ) consisting of membrane spanning proteins, connexins (Cx). It was demonstrated that IC and GJ in RPE and ROS cells can be reversibly blocked by gap-junction inhibitors such as heptanol or halothane. We demonstrated important differences in modulation of gap junctional communication between these cell types. While in RPE cells stimulation of PKC activity was able to inhibit IC, this was not the case in ROS cells. We screened LE-RPE cDNA via PCR using specific primers for different connexins and found no effect of high glucose solutions, which cause decreased intercellular communication, on the Cx-isoforms expressed. Cx43 is the only Cx-isoform present at the protein level for which Western blot analysis revealed the presence of different forms corresponding to different phosphorylated states. Increased phosphorylation of Cx43 was only seen after direct PKC activation by PMA, but not by indirect PKC activation by high glucose levels. The decreased communication by high glucose concentrations was however associated by a decreased expression of cellular Cx43 to about 3/4 of the level in control conditions. High glucose concentrations therefore decrease Cx43 at the protein level via a PKC effect that appears to be independent of the direct activation of PKC by phorbolesters. Mechanical stimulation did not evoke intercellular Ca(2+)-waves in LLC-PK1 epithelial cells, C6 glioma cells and MLO-Y4 osteocytes. In CPAE-endothelial cells, the contribution of gap junctions to IC following mechanical stimulation is negligible, and modulation of gap junctions via phosphorylation or high glucose solutions is absent. Perfusion experiments and pharmacological studies demonstrated that IC following mechanical stimulation of these cells occurs via release of an extracellular mediator. Our experiments provide strong evidence in favor of purinergic agonists as mediators, such as ATP but mainly ADP. In conclusion we can say that cells contain a wide spectrum of mechanisms for intra- and intercellular communication, and that widely different mechanisms can evoke the same phenomenon of intra- and intercellular Ca(2+)-waves. PMID- 11196580 TI - [Antisense constructs, therapeutics of the future?]. AB - Two lines of research were followed to obtain an adequate antisense effect. Natural oligonucleotides can degrade their mRNA targets catalytically, but are prone to enzymatic instability. Therefore, we looked for the minimal molecular modification, which would yield nuclease stable constructs, which can be taken up sufficiently to exert a selective antiproliferative effect. Small aliphatic diols conjugated at the 3'-end yielded such constructs, enabling selective tumor growth inhibition in an experimental in vivo situation. Further studies with complexing agents which increase their stability as well as uptake are ongoing. Another strategy aimed at obtaining strongly binding analogs, which would allow mRNA translation inhibition by steric interference. Hexitol nucleic acids (HNA) by virtue of their high and selective affinity for RNA, are therefore a prime candidate. When targeting the translation initiation regions, and using a lipofection protocol, nice activities were obtained at inhibiting Plasmodium, ICAM-1 and Ha-ras mRNA expression. Therefore, uptake should not be a limiting factor for the development of HNA as antisense therapeutics. PMID- 11196582 TI - Turing instabilities in general systems. AB - We present necessary and sufficient conditions on the stability matrix of a general n(> or = 2)-dimensional reaction-diffusion system which guarantee that its uniform steady state can undergo a Turing bifurcation. The necessary (kinetic) condition, requiring that the system be composed of an unstable (or activator) and a stable (or inhibitor) subsystem, and the sufficient condition of sufficiently rapid inhibitor diffusion relative to the activator subsystem are established in three theorems which form the core of our results. Given the possibility that the unstable (activator) subsystem involves several species (dimensions), we present a classification of the analytically deduced Turing bifurcations into p (1 < or = p < or = (n - 1)) different classes. For n = 3 dimensions we illustrate numerically that two types of steady Turing pattern arise in one spatial dimension in a generic reaction-diffusion system. The results confirm the validity of an earlier conjecture [12] and they also characterise the class of so-called strongly stable, matrices for which only necessary conditions have been known before [23, 24]. One of the main consequences of the present work is that biological morphogens, which have so far been expected to be single chemical species [1-9], may instead be composed of two or more interacting species forming an unstable subsystem. PMID- 11196581 TI - Asymptotics of the total net direct pharmacological effect for large drug doses. AB - The direct pharmacological effect E is described by the Emax model relating E to the drug plasma concentration Cp. The area under the effect vs. time curve (AUCE) is used as the measurement of the total net pharmacological effect. The drug plasma concentrations are solutions of compartmental systems of ordinary differential equations with the input terminated after a finite time and controlled in a proportional manner by a single dose-like parameter. The asymptotics of the time derivative of Cp for large doses are derived and used as conditions which have to be satisfied by functions for which the asymptotics of the integral defining AUCE are derived. The AUCE is proportional to the time TC > EC50 for which the drug concentration stays above the threshold level EC50. The threshold EC50 denotes the drug plasma concentration which elicits 50% of the maximum effect. The parameter TC > EC50 is proportional to the logarithm of drug dose for large doses and its asymptotics is calculated up to the order o(1) as dose increases to infinity. The results are applied to basic pharmacokinetic systems. PMID- 11196583 TI - Analysis of clustered firing patterns in synaptically coupled networks of oscillators. AB - Oscillators in networks may display a variety of activity patterns. This paper presents a geometric singular perturbation analysis of clustering, or alternate firing of synchronized subgroups, among synaptically coupled oscillators. We consideroscillators in two types of networks: mutually coupled, with all-to-all inhibitory connections, and globally inhibitory, with one excitatory and one inhibitory population of oscillators, each of arbitrary size. Our analysis yields existence and stability conditions for clustered states, along with formulas for the periods of such firing patterns. By using two different approaches, we derive complementary conditions, the first set stated in terms of time lengths determined by intrinsic and synaptic properties of the oscillators and their coupling and the second set stated in terms of model parameters and phase space structures directly linked to parameters. These results suggest how biological components may interact to produce the spindle sleep rhythm in thalamocortical networks. PMID- 11196584 TI - A new explicit stability criterion for human periodic breathing. AB - The aim of this paper is to carry out a stability analysis for periodic breathing in humans that incorporates the dynamic characteristics of ventilation control. A simple CO2 model that takes into account the main elements of the respiratory system, i.e. the lungs and the ventilatory controller with its dynamic properties, is presented. This model results in a three-dimensional non-linear delay differential system for which there exists a unique equilibrium point. Our stability analysis of this equilibrium point leads to the definition of a new explicit stability criterion and to the demonstration of the existence of a Hopf bifurcation. Numericall simulations illustrate the influence of physiological parameters on the stability of ventilation. and particularly the major role of the dynamic characteristics of the respiratory controller. PMID- 11196585 TI - Stochastic epidemics in dynamic populations: quasi-stationarity and extinction. AB - Empirical evidence shows that childhood diseases persist in large communities whereas in smaller communities the epidemic goes extinct (and is later reintroduced by immigration). The present paper treats a stochastic model describing the spread of an infectious disease giving life-long immunity, in a community where individuals die and new individuals are born. The time to extinction of the disease starting in quasi-stationarity (conditional on non extinction) is exponentially distributed. As the population size grows the epidemic process converges to a diffusion process. Properties of the limiting diffusion are used to obtain an approximate expression for tau, the mean parameter in the exponential distribution of the time to extinction for the finite population. The expression is used to study how tau depends on the community size but also on certain properties of the disease/community: the basic reproduction number and the means and variances of the latency period, infectious period and life-length. Effects of introducing a vaccination program are also discussed as is the notion of the critical community size, defined as the size which distinguishes between the two qualitatively different behaviours. PMID- 11196586 TI - [Vasculitis: are we talking about the same thing?]. PMID- 11196587 TI - [Respiratory complications in hematopoietic stem cell transplantation. What does radiology contribute?]. AB - OBJECTIVE: To determine the incidence of respiratory complications and their manifestations in both conventional radiology and high-resolution computerized tomography (HRCT) in a series of patients who had undergone blood progenitor cell transplantation (BPCT). The objective was to evaluate whether the radiological findings associated with post-transplantation time can be useful for establishing the differential diagnosis. PATIENTS AND METHODS: A study was undertaken of a total of 108 consecutive patients who had undergone BPCT and were alive one year after; from these patients a selection was made of those who had some respiratory complications during the first year after transplantation. Complications were classified in three different groups on the basis of time elapsed since transplantation (early, intermediate, and late stages). Chest X-ray films of each patient were examined and in 17 cases the study was completed with HRCT. These findings were correlated with both definitive diagnosis and time elapsed since BPCT. The following procedures were useful for diagnostic confirmation: blood culture, sputum culture, fibrobronchoscopy with bronchoalveolar lavage or lung biopsy, biopsy by other methods, necropsy, or clinical course after empirical therapy. RESULTS: Thirty-three out of the 108 patients undergoing BPCT had some form of respiratory complication during the first year after transplantation. The most common radiological pattern both in the chest X-ray and in HRCT was alveolar consolidation. Other findings included ground-glass appearance, interstitial pattern, pulmonary nodules, and pleural effusion. The diagnoses in relation to the different stages of transplantation were: a) early stage: three cases of heart failure, two cases of alveolar hemorrhage, two cases of pulmonary aspergillosis and three cases of undocumented complications; b) intermediate stage: four cases of cytomegalovirus pneumonia, one case of pulmonary aspergillosis, two cases of bacterial pneumonia, and two cases of undocumented pneumonitis; c) late stage: four cases of bacteriologically documented pneumonia, two cases of pneumonitis with an unidentified agent, two cases of graft-versus host disease, one case of pulmonary aspergillosis and two complications without established diagnosis. CONCLUSIONS: The relationship between radiological findings and time elapsed since transplantation of blood precursor cells is very useful for establishing the diagnosis of pulmonary complications. High resolution computerized tomography is useful for detecting unnoticed lesions in conventional X-ray, and for diagnosing bronchiolitis obliterans and some fungal lesions. PMID- 11196588 TI - [Churg-Strauss syndrome. Our experience in 2 decades]. AB - BACKGROUND: Since 1951, the year when the Churg-Strauss syndrome was reported, several isolated cases have been reported in the literature but works containing a high number of cases are exceptional. The features of the syndrome as well as diagnostic criteria have not been contrasted in large series. We therefore tried to analyze these parameters in 16 patients diagnosed of Churg-Strauss syndrome at our hospital. METHODS: A retrospective analysis was made of 16 patients diagnosed of Churg-Strauss syndrome at Hospital Universitario La Paz from 1978 at 1998. Data regarding personal antecedents, clinical manifestations, analytical parameters, histology and clinical course were collected. Also, the main diagnostic criteria reported in the literature were applied to each case. RESULTS: Of the 16 cases, thirteen (81%) were women, six were diagnosed at an age between 21 and 40 years; other six cases from 51 to 70 years. All patients had antecedents of bronchial asthma. Among clinical manifestations, 60% had fever and 50% a general syndrome. The main involved organs by decreasing frequency were lung (100%), nervous system (63%), and heart (44%). The mean eosinophilic count was 7,640/mm3. The histological diagnosis was obtained in 14 out of the 16 patients (88%). The most efficient biopsies corresponded to muscle and nerve. After therapy, no relapse was noted of vasculitis although bronchial asthma persisted in most patients (12). Twelve cases (75%) fulfilled the Lanham diagnostic criteria. CONCLUSIONS: Churg-Strauss syndrome affects mainly women with severe eosinophilia. Electromyogram and muscle and peripheral nerve biopsy are useful tools for diagnosis. The Lanham criteria lead to the diagnosis in most patients. PMID- 11196589 TI - [Collagenous colitis: an entity with diverse therapeutic options]. AB - Collagenous colitis is a disorder which has been diagnosed with increasing frequency in the last few years, probably due to the routine obtention of colon biopsy specimens in the study of patients with chronic diarrhoea. Good responses have been reported with a number of therapies, although only a scarce number of clinical trials have been performed, partly because of the small number of patients studied. Two cases of collagenous colitis with different therapeutic approaches are here reported. All medical therapy options for this interesting disorder are reviewed. PMID- 11196590 TI - [Colorectal cancer: inducing circumstances (etiology) and pathogenic paths (pathogenesis]. PMID- 11196591 TI - [Diarrhea of nosocomial origin in an adult population]. PMID- 11196592 TI - [Vaccinations in the patient infected with the human immunodeficiency virus]. PMID- 11196593 TI - [Indications for the pharmacologic treatment of hyperlipidemias]. PMID- 11196594 TI - [Diagnostic management of syncope]. PMID- 11196595 TI - [A patient with dyspnea and pain in the right thigh]. PMID- 11196596 TI - [Progressively appearing hyperpigmented macules in a patient treated with furosemide]. PMID- 11196597 TI - [Exanthema in a patient infected with the human immunodeficiency virus after starting antiretroviral treatment]. PMID- 11196598 TI - [Necrotic plaques in a patient with chronic renal insufficiency]. PMID- 11196599 TI - [Prostatic infiltration by non-Hodgkin's lymphoma: report of a case]. PMID- 11196600 TI - [Human myiasis caused by Sarcophagidae sp. (Diptera) in a post-irradiation ulcerative lesion after treatment for an axillary epidermoid carcinoma]. PMID- 11196601 TI - [Diffuse large cell B lymphoma presenting as clinicohistologic lymphadenopathy]. PMID- 11196602 TI - [Abrupt decrease in visual acuity in the course of acute pancreatitis]. PMID- 11196603 TI - [Isolation of human herpesvirus type 6 in the blood of patients receiving a renal transplant]. PMID- 11196604 TI - Is the university-industrial complex out of control? PMID- 11196605 TI - Scepticism greets claims that uranium shells cause leukaemia. PMID- 11196606 TI - Dye dispute leans Amersham's way. PMID- 11196607 TI - Overseas investors plan six 'world class' universities in India. PMID- 11196609 TI - Canadian astronomers mount lobby effort. PMID- 11196608 TI - Bush targets space-based missile defence system. PMID- 11196610 TI - Scientists unimpressed by Australia's funding plan. PMID- 11196611 TI - US to take temperature of mercury threat. PMID- 11196612 TI - Hunt for Earth-like planets edges towards launch pad. PMID- 11196613 TI - Moderate takes key science role in Congress. PMID- 11196614 TI - Biologists crusade for evolution. PMID- 11196615 TI - Save our swamp. PMID- 11196616 TI - Sensitive development could protect Amazonia instead of destroying it. PMID- 11196617 TI - How electricity could power the car of today. PMID- 11196618 TI - Did agriculture reduce human lifespan? PMID- 11196619 TI - You can't have it all. PMID- 11196621 TI - The dark cradles of stars. PMID- 11196620 TI - Food, song and speciation. PMID- 11196622 TI - Haemoglobin scavenger. PMID- 11196623 TI - Cancer. Death and methylation. PMID- 11196624 TI - Earth science. In the beginning... PMID- 11196625 TI - Cardiovascular biology. Small cells, big issues. PMID- 11196626 TI - Climatology. Glacial hiccups. PMID- 11196627 TI - An enzymic 'latch' on a global carbon store. PMID- 11196628 TI - Cross-modal plasticity and cochlear implants. PMID- 11196629 TI - Networks of nanotubes and containers. PMID- 11196630 TI - Worms start the reef-building process. PMID- 11196631 TI - Rapid changes of glacial climate simulated in a coupled climate model. AB - Abrupt changes in climate, termed Dansgaard-Oeschger and Heinrich events, have punctuated the last glacial period (approximately 100-10 kyr ago) but not the Holocene (the past 10 kyr). Here we use an intermediate-complexity climate model to investigate the stability of glacial climate, and we find that only one mode of Atlantic Ocean circulation is stable: a cold mode with deep water formation in the Atlantic Ocean south of Iceland. However, a 'warm' circulation mode similar to the present-day Atlantic Ocean is only marginally unstable, and temporary transitions to this warm mode can easily be triggered. This leads to abrupt warm events in the model which share many characteristics of the observed Dansgaard Oeschger events. For a large freshwater input (such as a large release of icebergs), the model's deep water formation is temporarily switched off, causing no strong cooling in Greenland but warming in Antarctica, as is observed for Heinrich events. Our stability analysis provides an explanation why glacial climate is much more variable than Holocene climate. PMID- 11196632 TI - Internal structure of a cold dark molecular cloud inferred from the extinction of background starlight. AB - Stars and planets form within dark molecular clouds, but little is understood about the internal structure of these clouds, and consequently about the initial conditions that give rise to star and planet formation. The clouds are primarily composed of molecular hydrogen, which is virtually inaccessible to direct observation. But the clouds also contain dust, which is well mixed with the gas and which has well understood effects on the transmission of light. Here we use sensitive near-infrared measurements of the light from background stars as it is absorbed and scattered by trace amounts of dust to probe the internal structure of the dark cloud Barnard 68 with unprecedented detail. We find the cloud's density structure to be very well described by the equations for a pressure confined, self-gravitating isothermal sphere that is critically stable according to the Bonnor-Ebert criteria. As a result we can precisely specify the physical conditions inside a dark cloud on the verge of collapse to form a star. PMID- 11196633 TI - Quantum metallicity in a two-dimensional insulator. AB - One of the most far-reaching problems in condensed-matter physics is to understand how interactions between electrons, and the resulting correlations, affect the electronic properties of disordered two-dimensional systems. Extensive experimental and theoretical studies have shown that interaction effects are enhanced by disorder, and that this generally results in a depletion of the density of electronic states. In the limit of strong disorder, this depletion takes the form of a complete gap in the density of states. It is known that this 'Coulomb gap' can turn a pure metal film that is highly disordered into a poorly conducting insulator, but the properties of these insulators are not well understood. Here we investigate the electronic properties of disordered beryllium films, with the aim of disentangling the effects of the Coulomb gap and the underlying disorder. We show that the gap is suppressed by a magnetic field and that this drives the strongly insulating beryllium films into a low-temperature 'quantum metal' phase with resistance near the quantum resistance RQ = h/e2, where h is Planck's constant and e is the electron charge. PMID- 11196634 TI - The relationship between fragility, configurational entropy and the potential energy landscape of glass-forming liquids. AB - Glass is a microscopically disordered, solid form of matter that results when a fluid is cooled or compressed in such a manner that it does not crystallize. Almost all types of materials are capable of glass formation, including polymers, metal alloys and molten salts. Given such diversity, general principles by which different glass-forming materials can be systematically classified are invaluable. One such principle is the classification of glass-formers according to their fragility. Fragility measures the rapidity with which a liquid's properties (such as viscosity) change as the glassy state is approached. Although the relationship between the fragility, configurational entropy and features of the energy landscape (the complicated dependence of energy on configuration) of a glass-former have been analysed previously, a detailed understanding of the origins of fragility is lacking. Here I use simulations to analyse the relationship between fragility and quantitative measures of the energy landscape for a model liquid whose fragility depends on its bulk density. The results reveal that fragility depends on changes in the vibrational properties of individual energy minima in addition to their total number and spread in energy. A thermodynamic expression for fragility is derived, which is in quantitative agreement with kinetic fragilities obtained from the liquid's diffusivity. PMID- 11196635 TI - Observation of shear-induced nematic-isotropic transition in side-chain liquid crystal polymers. AB - Flow-induced phase transitions are a fundamental (but poorly understood) property of non-equilibrium systems, and are also of practical importance for tuning the processing conditions for plastics, petroleum products, and other related materials. Recognition that polymers may exhibit liquid crystal properties has led to the discovery of the first tailored side-chain liquid crystal polymers (SCLCPs), which are formed by inserting a spacer between the main polymer chain and the lateral mesogen liquid-crystalline graftings. Subsequent research has sought to understand the nature of the coupling between the main polymer chain and the mesogens, with a view to obtaining better control of the properties of these tailored structures. We show here that the parallel or perpendicular orientation of the mesogens with respect to the main chain can be reversed by the application of an external field produced by a shear flow, demonstrating the existence of an isotropic nematic phase transition in SCLCPs. Such a transition, which was theoretically predicted for low-molecular-weight liquid crystals but never observed, is shown to be a general property of SCLCPs too. We expect that these SCLCPs will prove to be good candidate systems for the experimental study of these non-equilibrium phenomena. PMID- 11196636 TI - An abrupt climate event in a coupled ocean-atmosphere simulation without external forcing. AB - Temperature reconstructions from the North Atlantic region indicate frequent abrupt and severe climate fluctuations during the last glacial and Holocene periods. The driving forces for these events are unclear and coupled atmosphere ocean models of global circulation have only simulated such events by inserting large amounts of fresh water into the northern North Atlantic Ocean. Here we report a drastic cooling event in a 15,000-yr simulation of global circulation with present-day climate conditions without the use of such external forcing. In our simulation, the annual average surface temperature near southern Greenland spontaneously fell 6-10 standard deviations below its mean value for a period of 30-40 yr. The event was triggered by a persistent northwesterly wind that transported large amounts of buoyant cold and fresh water into the northern North Atlantic Ocean. Oceanic convection shut down in response to this flow, concentrating the entire cooling of the northern North Atlantic by the colder atmosphere in the uppermost ocean layer. Given the similarity between our simulation and observed records of rapid cooling events, our results indicate that internal atmospheric variability alone could have generated the extreme climate disruptions in this region. PMID- 11196637 TI - Evidence from detrital zircons for the existence of continental crust and oceans on the Earth 4.4 Gyr ago. AB - No crustal rocks are known to have survived since the time of the intense meteor bombardment that affected Earth between its formation about 4,550 Myr ago and 4,030 Myr, the age of the oldest known components in the Acasta Gneiss of northwestern Canada. But evidence of an even older crust is provided by detrital zircons in metamorphosed sediments at Mt Narryer and Jack Hills in the Narryer Gneiss Terrane, Yilgarn Craton, Western Australia, where grains as old as approximately 4,276 Myr have been found. Here we report, based on a detailed micro-analytical study of Jack Hills zircons, the discovery of a detrital zircon with an age as old as 4,404+/-8 Myr--about 130 million years older than any previously identified on Earth. We found that the zircon is zoned with respect to rare earth elements and oxygen isotope ratios (delta18O values from 7.4 to 5.0%), indicating that it formed from an evolving magmatic source. The evolved chemistry, high delta18O value and micro-inclusions of SiO2 are consistent with growth from a granitic melt with a delta18O value from 8.5 to 9.5%. Magmatic oxygen isotope ratios in this range point toward the involvement of supracrustal material that has undergone low-temperature interaction with a liquid hydrosphere. This zircon thus represents the earliest evidence for continental crust and oceans on the Earth. PMID- 11196638 TI - Oxygen-isotope evidence from ancient zircons for liquid water at the Earth's surface 4,300 Myr ago. AB - Granitoid gneisses and supracrustal rocks that are 3,800-4,000 Myr old are the oldest recognized exposures of continental crust. To obtain insight into conditions at the Earth's surface more than 4 Gyr ago requires the analysis of yet older rocks or their mineral remnants. Such an opportunity is presented by detrital zircons more than 4 Gyr old found within 3-Gyr-old quartzitic rocks in the Murchison District of Western Australia. Here we report in situ U-Pb and oxygen isotope results for such zircons that place constraints on the age and composition of their sources and may therefore provide information about the nature of the Earth's early surface. We find that 3,910-4,280 Myr old zircons have oxygen isotope (delta18O) values ranging from 5.4+/-0.6% to 15.0+/-0.4%. On the basis of these results, we postulate that the approximately 4,300-Myr-old zircons formed from magmas containing a significant component of re-worked continental crust that formed in the presence of water near the Earth's surface. These data are therefore consistent with the presence of a hydrosphere interacting with the crust by 4,300 Myr ago. PMID- 11196639 TI - Fossil that fills a critical gap in avian evolution. AB - Despite the discoveries of well-preserved Mesozoic birds, a key part of avian evolution, close to the radiation of all living birds (Aves), remains poorly represented. Here we report on a new taxon from the Late Cretaceous locality of Ukhaa Tolgod, Mongolia, that offers insight into this critically unsampled period. Apsaravis and the controversial alvarezsaurids are the only avialan taxa known from the continental deposits at Ukhaa Tolgod, which have produced hundreds of fossil mammals, lizards and other small dinosaurs. The new taxon, Apsaravis ukhaana, is the best-preserved specimen of a Mesozoic ornithurine bird discovered in over a century. It provides data important for assessing morphological evolution across Avialae, with implications for, first, the monophyly of Enantiornithes and Sauriurae; second, the proposition that the Mesozoic sister taxa of extant birds, as part of an 'ecological bottleneck', inhabited exclusively near-shore and marine environments; and third, the evolution of flight after its origin. PMID- 11196640 TI - Correlated evolution of morphology and vocal signal structure in Darwin's finches. AB - Speciation in many animal taxa is catalysed by the evolutionary diversification of mating signals. According to classical theories of speciation, mating signals diversify, in part, as an incidental byproduct of adaptation by natural selection to divergent ecologies, although empirical evidence in support of this hypothesis has been limited. Here I show, in Darwin's finches of the Galapagos Islands, that diversification of beak morphology and body size has shaped patterns of vocal signal evolution, such that birds with large beaks and body sizes have evolved songs with comparatively low rates of syllable repetition and narrow frequency bandwidths. The converse is true for small birds. Patterns of correlated evolution among morphology and song are consistent with the hypothesis that beak morphology constrains vocal evolution, with different beak morphologies differentially limiting a bird's ability to modulate vocal tract configurations during song production. These data illustrate how morphological adaptation may drive signal evolution and reproductive isolation, and furthermore identify a possible cause for rapid speciation in Darwin's finches. PMID- 11196641 TI - Nitrogen limitation of microbial decomposition in a grassland under elevated CO2. AB - Carbon accumulation in the terrestrial biosphere could partially offset the effects of anthropogenic CO2 emissions on atmospheric CO2. The net impact of increased CO2 on the carbon balance of terrestrial ecosystems is unclear, however, because elevated CO2 effects on carbon input to soils and plant use of water and nutrients often have contrasting effects on microbial processes. Here we show suppression of microbial decomposition in an annual grassland after continuous exposure to increased CO2 for five growing seasons. The increased CO2 enhanced plant nitrogen uptake, microbial biomass carbon, and available carbon for microbes. But it reduced available soil nitrogen, exacerbated nitrogen constraints on microbes, and reduced microbial respiration per unit biomass. These results indicate that increased CO2 can alter the interaction between plants and microbes in favour of plant utilization of nitrogen, thereby slowing microbial decomposition and increasing ecosystem carbon accumulation. PMID- 11196642 TI - Regulation of the gain of visually guided smooth-pursuit eye movements by frontal cortex. AB - In studies of the neural mechanisms giving rise to behaviour, changes in the neural and behavioural responses produced by a given stimulus have been widely reported. This 'gain control' can boost the responses to sensory inputs that are particularly relevant, select among reflexes for execution by motoneurons or emphasize specific movement targets. Gain control is also an integral part of the smooth-pursuit eye movement system. One signature of gain control is that a brief perturbation of a stationary target during fixation causes tiny eye movements, whereas the same perturbation of a moving target during the active state of accurate pursuit causes large responses. Here we show that electrical stimulation of the smooth-pursuit eye movement region in the arcuate sulcus of the frontal lobe ('the frontal pursuit area', FPA) mimics the active state of pursuit. Such stimulation enhances the response to a brief perturbation of target motion, regardless of the direction of motion. We postulate that the FPA sets the gain of pursuit, thereby participating in target selection for pursuit. PMID- 11196643 TI - A role for ghrelin in the central regulation of feeding. AB - Ghrelin is an acylated peptide that stimulates the release of growth hormone from the pituitary. Ghrelin-producing neurons are located in the hypothalamus, whereas ghrelin receptors are expressed in various regions of the brain, which is indicative of central-and as yet undefined-physiological functions. Here we show that ghrelin is involved in the hypothalamic regulation of energy homeostasis. Intracerebroventricular injections of ghrelin strongly stimulated feeding in rats and increased body weight gain. Ghrelin also increased feeding in rats that are genetically deficient in growth hormone. Anti-ghrelin immunoglobulin G robustly suppressed feeding. After intracerebroventricular ghrelin administration, Fos protein, a marker of neuronal activation, was found in regions of primary importance in the regulation of feeding, including neuropeptide Y6 (NPY) neurons and agouti-related protein (AGRP) neurons. Antibodies and antagonists of NPY and AGRP abolished ghrelin-induced feeding. Ghrelin augmented NPY gene expression and blocked leptin-induced feeding reduction, implying that there is a competitive interaction between ghrelin and leptin in feeding regulation. We conclude that ghrelin is a physiological mediator of feeding, and probably has a function in growth regulation by stimulating feeding and release of growth hormone. PMID- 11196644 TI - Identification of the haemoglobin scavenger receptor. AB - Intravascular haemolysis is a physiological phenomenon as well as a severe pathological complication when accelerated in various autoimmune, infectious (such as malaria) and inherited (such as sickle cell disease) disorders. Haemoglobin released into plasma is captured by the acute phase protein haptoglobin, which is depleted from plasma during elevated haemolysis. Here we report the identification of the acute phase-regulated and signal-inducing macrophage protein, CD163, as a receptor that scavenges haemoglobin by mediating endocytosis of haptoglobin-haemoglobin complexes. CD163 binds only haptoglobin and haemoglobin in complex, which indicates the exposure of a receptor-binding neoepitope. The receptor-ligand interaction is Ca2+-dependent and of high affinity. Complexes of haemoglobin and multimeric haptoglobin (the 2-2 phenotype) exhibit higher functional affinity for CD 163 than do complexes of haemoglobin and dimeric haptoglobin (the 1-1 phenotype). Specific CD163-mediated endocytosis of haptoglobin-haemoglobin complexes is measurable in cells transfected with CD163 complementary DNA and in CD163-expressing myelo-monocytic lymphoma cells. PMID- 11196645 TI - Identification of the platelet ADP receptor targeted by antithrombotic drugs. AB - Platelets have a crucial role in the maintenance of normal haemostasis, and perturbations of this system can lead to pathological thrombus formation and vascular occlusion, resulting in stroke, myocardial infarction and unstable angina. ADP released from damaged vessels and red blood cells induces platelet aggregation through activation of the integrin GPIIb-IIIa and subsequent binding of fibrinogen. ADP is also secreted from platelets on activation, providing positive feedback that potentiates the actions of many platelet activators. ADP mediates platelet aggregation through its action on two G-protein-coupled receptor subtypes. The P2Y1 receptor couples to Gq and mobilizes intracellular calcium ions to mediate platelet shape change and aggregation. The second ADP receptor required for aggregation (variously called P2Y(ADP), P2Y(AC), P2Ycyc or P2T(AC)) is coupled to the inhibition of adenylyl cyclase through Gi. The molecular identity of the Gi-linked receptor is still elusive, even though it is the target of efficacious antithrombotic agents, such as ticlopidine and clopidogrel and AR-C66096 (ref. 9). Here we describe the cloning of this receptor, designated P2Y12, and provide evidence that a patient with a bleeding disorder has a defect in this gene. Cloning of the P2Y12 receptor should facilitate the development of better antiplatelet agents to treat cardiovascular diseases. PMID- 11196646 TI - Inactivation of the apoptosis effector Apaf-1 in malignant melanoma. AB - Metastatic melanoma is a deadly cancer that fails to respond to conventional chemotherapy and is poorly understood at the molecular level. p53 mutations often occur in aggressive and chemoresistant cancers but are rarely observed in melanoma. Here we show that metastatic melanomas often lose Apaf-1, a cell-death effector that acts with cytochrome c and caspase-9 to mediate p53-dependent apoptosis. Loss of Apaf-1 expression is accompanied by allelic loss in metastatic melanomas, but can be recovered in melanoma cell lines by treatment with the methylation inhibitor 5-aza-2'-deoxycytidine (5aza2dC). Apaf-1-negative melanomas are invariably chemoresistant and are unable to execute a typical apoptotic programme in response to p53 activation. Restoring physiological levels of Apaf-1 through gene transfer or 5aza2dC treatment markedly enhances chemosensitivity and rescues the apoptotic defects associated with Apaf-1 loss. We conclude that Apaf 1 is inactivated in metastatic melanomas, which leads to defects in the execution of apoptotic cell death. Apaf-1 loss may contribute to the low frequency of p53 mutations observed in this highly chemoresistant tumour type. PMID- 11196647 TI - The protein-protein interaction map of Helicobacter pylori. AB - With the availability of complete DNA sequences for many prokaryotic and eukaryotic genomes, and soon for the human genome itself, it is important to develop reliable proteome-wide approaches for a better understanding of protein function. As elementary constituents of cellular protein complexes and pathways, protein-protein interactions are key determinants of protein function. Here we have built a large-scale protein-protein interaction map of the human gastric pathogen Helicobacter pylori. We have used a high-throughput strategy of the yeast two-hybrid assay to screen 261 H. pylori proteins against a highly complex library of genome-encoded polypeptides. Over 1,200 interactions were identified between H. pylori proteins, connecting 46.6% of the proteome. The determination of a reliability score for every single protein-protein interaction and the identification of the actual interacting domains permitted the assignment of unannotated proteins to biological pathways. PMID- 11196648 TI - Crystal structures of SarA, a pleiotropic regulator of virulence genes in S. aureus. AB - Staphylococcus aureus is a major human pathogen, the potency of which can be attributed to the regulated expression of an impressive array of virulence determinants. A key pleiotropic transcriptional regulator of these virulence factors is SarA, which is encoded by the sar (staphylococcal accessory regulator) locus. SarA was characterized initially as an activator of a second virulence regulatory locus, agr, through its interaction with a series of heptad repeats (AGTTAAG) within the agr promoter. Subsequent DNA-binding studies have revealed that SarA binds readily to multiple AT-rich sequences of variable lengths. Here we describe the crystal structure of SarA and a SarA-DNA complex at resolutions of 2.50 A and 2.95 A, respectively. SarA has a fold consisting of a four-helix core region and 'inducible regions' comprising a beta-hairpin and a carboxy terminal loop. On binding DNA, the inducible regions undergo marked conformational changes, becoming part of extended and distorted alpha-helices, which encase the DNA. SarA recognizes an AT-rich site in which the DNA is highly overwound and adopts a D-DNA-like conformation by indirect readout. These structures thus provide insight into SarA-mediated transcription regulation. PMID- 11196649 TI - Projection structure of a ClC-type chloride channel at 6.5 A resolution. AB - Virtually all cells in all eukaryotic organisms express ion channels of the ClC type, the only known molecular family of chloride-ion-selective channels. The diversity of ClC channels highlights the multitude and range of functions served by gated chloride-ion conduction in biological membranes, such as controlling electrical excitability in skeletal muscle, maintaining systemic blood pressure, acidifying endosomal compartments, and regulating electrical responses of GABA (gamma-aminobutyric acid)-containing interneurons in the central nervous system. Previously, we expressed and purified a prokaryotic ClC channel homologue. Here we report the formation of two-dimensional crystals of this ClC channel protein reconstituted into phospholipid bilayer membranes. Cryo-electron microscopic analysis of these crystals yields a projection structure at 6.5 A resolution, which shows off-axis water-filled pores within the dimeric channel complex. PMID- 11196650 TI - Enabling the chemistry of life. AB - Enzymes are the subset of proteins that catalyse the chemistry of life, transforming both macromolecular substrates and small molecules. The precise three-dimensional architecture of enzymes permits almost unerring selectivity in physical and chemical steps to impose remarkable rate accelerations and specificity in product-determining reactions. Many enzymes are members of families that carry out related chemical transformations and offer opportunities for directed in vitro evolution, to tailor catalytic properties to particular functions. PMID- 11196652 TI - Improving enzymes by using them in organic solvents. AB - The technological utility of enzymes can be enhanced greatly by using them in organic solvents rather than their natural aqueous reaction media. Studies over the past 15 years have revealed not only that this change in solvent is feasible, but also that in such seemingly hostile environments enzymes can catalyse reactions impossible in water, become more stable, and exhibit new behaviour such as 'molecular memory'. Of particular importance has been the discovery that enzymatic selectivity, including substrate, stereo-, regio- and chemoselectivity, can be markedly affected, and sometimes even inverted, by the solvent. Enzyme catalysed reactions in organic solvents, and even in supercritical fluids and the gas phase, have found numerous potential applications, some of which are already commercialized. PMID- 11196651 TI - Enzymes for chemical synthesis. AB - New catalytic synthetic methods in organic chemistry that satisfy increasingly stringent environmental constraints are in great demand by the pharmaceutical and chemical industries. In addition, novel catalytic procedures are necessary to produce the emerging classes of organic compounds that are becoming the targets of molecular and biomedical research. Enzyme-catalysed chemical transformations are now widely recognized as practical alternatives to traditional (non biological) organic synthesis, and as convenient solutions to certain intractable synthetic problems. PMID- 11196653 TI - Modular enzymes. AB - Although modular macromolecular devices are encountered frequently in a variety of biological situations, their occurrence in biocatalysis has not been widely appreciated. Three general classes of modular biocatalysts can be identified: enzymes in which catalysis and substrate specificity are separable, multisubstrate enzymes in which binding sites for individual substrates are modular, and multienzyme systems that can catalyse programmable metabolic pathways. In the postgenomic era, the discovery of such systems can be expected to have a significant impact on the role of enzymes in synthetic and process chemistry. PMID- 11196654 TI - Combinatorial and computational challenges for biocatalyst design. AB - Nature provides a fantastic array of catalysts extremely well suited to supporting life, but usually not so well suited for technology. Whether biocatalysis will have a significant technological impact depends on our finding robust routes for tailoring nature's catalysts or redesigning them anew. Laboratory evolution methods are now used widely to fine-tune the selectivity and activity of enzymes. The current rapid development of these combinatorial methods promises solutions to more complex problems, including the creation of new biosynthetic pathways. Computational methods are also developing quickly. The marriage of these approaches will allow us to generate the efficient, effective catalysts needed by the pharmaceutical, food and chemicals industries and should open up new opportunities for producing energy and chemicals from renewable resources. PMID- 11196655 TI - Industrial biocatalysis today and tomorrow. AB - The use of biocatalysis for industrial synthetic chemistry is on the verge of significant growth. Biocatalytic processes can now be carried out in organic solvents as well as aqueous environments, so that apolar organic compounds as well as water-soluble compounds can be modified selectively and efficiently with enzymes and biocatalytically active cells. As the use of biocatalysis for industrial chemical synthesis becomes easier, several chemical companies have begun to increase significantly the number and sophistication of the biocatalytic processes used in their synthesis operations. PMID- 11196656 TI - The AT-rich region between -54 to -66 is important for the promoter activity of interleukin-10 in Epstein-Barr virus positive Burkitt's lymphoma cells. AB - IL-10 is an important regulatory cytokine. The recent characterization of the 5' flanking region of IL-10 led to the identification of the promoter region. The infection of B cells with EBV induces IL-10 production which may contribute to EBV-induced transformation. In the present report, IL-10 promoter elements involved in the constitutive expression of IL-10 in EBV-positive lymphoma cells are described. The AT-rich region between -54/-66 from the transcriptional start site was found to be important for IL-10-promoter activity in BL36. A point mutation at position -60 (T/A) was associated with over 90% reduction of luciferase activity in the cell lines BL36 and BL74. The conversion of A/T at position -57 led to enhanced promoter activity. In addition the AT-rich region could serve as an enhancer for the beta-globin basic promoter. In BJAB cells (EBV negative), sequences between -205/-139 rather than the AT-rich region were involved in IL-10 promoter regulation. This underlines the importance of the AT rich region for EBV-associated IL-10 promoter regulation. Our results further the understanding of how the IL-10 gene could be regulated in B cell lymphomas. PMID- 11196657 TI - Allelic variants in the interleukin-6 gene and essential hypertension in Japanese women. AB - Genes that can be implicated in hypertension in experimental animals are plausible candidates in the pathogenesis of human hypertension. A recent genome wide search for quantitative-trait loci (QTL) in hypertensive rats revealed a strong correlation between the interleukin-6 (IL-6) locus on rat chromosome 4 and systolic, diastolic, and mean arterial pressure in this mammalian species. To investigate a possible association between genetic variations of the IL-6 gene and hypertension in humans, we identified two novel single-nucleotide sequence variations, a C/G substitution at -634 in the promoter region and a G/A substitution at 4391 in a 3' non-coding portion of exon 5, and a previous reported sequence variant, an A/T variation in the composition of the AnTn tract around -447 in the promoter region (Fishman D et al. J Clin Invest 1998; 102: 1369-1376), within a test population of 96 Japanese subjects. Allelic associations involving these variations were analyzed in 150 hypertensive and 143 normotensive Japanese women. The distribution of alleles of the three polymorphisms, as well as a dinucleotide repeat present at the IL-6 locus, was similar in the two groups. Therefore, the IL-6 gene appears to play a minimal role in the genetic etiology of essential hypertension in Japanese women. PMID- 11196658 TI - Taxonomic hierarchy of HLA class I allele sequences. AB - The markedly high levels of polymorphism present in classical class I loci of the human major histocompatibility complex have been implicated in infectious and immune disease recognition. The large numbers of alleles present at these loci have, however, limited efforts to verify associations between individual alleles and specific diseases. As an approach to reduce allele diversity to hierarchical evolutionarily related groups, we performed phylogenetic analyses of available HLA-A, B and C allele complete sequences (n = 216 alleles) using different approaches (maximum parsimony, distance-based minimum evolution and maximum likelihood). Full nucleotide and amino acid sequences were considered as well as abridged sequences from the hypervariable peptide binding region, known to interact in vivo, with HLA presented foreign peptide. The consensus analyses revealed robust clusters of 36 HLA-C alleles concordant for full and PBR sequence analyses. HLA-A alleles (n = 60) assorted into 12 groups based on full nucleotide and amino acid sequence which with few exceptions recapitulated serological groupings, however the patterns were largely discordant with clusters prescribed by PBR sequences. HLA-B which has the most alleles (n = 120) and which unlike HLA A and -C is thought to be subject to frequent recombinational exchange, showed limited phylogenetic structure consistent with recent selection driven retention of maximum heterozygosity and population diversity. Those allele categories recognized offer an explicit phylogenetic criterion for grouping alleles potentially relevant for epidemiologic associations, for inferring the origin of MHC genome organization, and for comparing functional constraints in peptide presentation of HLA alleles. PMID- 11196659 TI - Genetic polymorphism of murine tissue plasminogen activator associated with antiphospholipid syndrome. AB - In a subset of patients with systemic lupus erythematosus (SLE), antiphospholipid syndrome characterized by thrombocytopenia, thrombosis, recurrent abortion and antiphospholipid antibodies develops. Male (NZW x BXSB) F1 mice are widely used as a model for SLE-associated antiphospholipid syndrome. Our earlier genetic studies showed that one susceptibility allele for thrombocytopenia and associated IgG platelet-binding autoantibodies in male (NZW x BXSB) F1 mice was linked to the BXSB-type polymorphic microsatellite D8Mit96, located in proximity to the gene Plat for tissue-type plasminogen activator (t-PA). In the present studies, sequence analyses for structural and promoter regions of Plat revealed a single nucleotide polymorphism encoding a catalytic domain of t-PA, with an amino acid substitution of anionic Glu366 in NZW for a cationic Lys in BXSB. Progeny studies using NZW x (NZW x BXSB) F1 male backcross mice showed that the BXSB Plat allele was significantly associated with high levels of both platelet-binding antibodies and thrombocytopenia. Furthermore, these two traits appeared to be regulated by a complementary effect of two BXSB alleles; one is linked to Plat and the other to the H-2 complex and the gene for plasminogen. Thus, the BXSB-type Plat may be one susceptibility allele for the multigenic antiphospholipid syndrome seen in (NZW x BXSB) F1 mice. Potential mechanisms are discussed. PMID- 11196660 TI - Variation in immunoregulatory genes determines the clinical phenotype of common variable immunodeficiency. AB - Variation in clinical phenotype is a hallmark of many complex diseases. The cause of this clinical heterogeneity is unknown, but it may be determined by genetic factors distinct from those conferring disease susceptibility. Common variable immunodeficiency (CVID) is a complex disease of unknown aetiology and diverse clinical manifestations. We have developed a unified polymerase chain reaction and sequence-specific primer (PCR-SSP) method to simultaneously genotype multiple polymorphisms under identical conditions, and have used this method to test the hypothesis that the clinical phenotype of CVID is determined by immunoregulatory gene polymorphism. Twenty-three polymorphisms in 13 genes were studied in 163 CVID patients. Vitamin D receptor and IL-6 alleles were associated with immunophenotypic abnormalities characteristic of more severe disease; and tumour necrosis factor and IL-10 alleles conferred susceptibility to the granulomatous form of CVID in an interacting fashion. These findings demonstrate that different clinical features of a disease may have unique pathogenetic abnormalities, determined by multiple interacting genetic factors. The ease of application of this efficient, robust genotyping technique to polymorphisms throughout the genome will make it a powerful tool in the investigation of the genetic basis of phenotypic variability in a wide variety of diseases. PMID- 11196661 TI - Chromosome 17q22-q24 and multiple sclerosis genetic susceptibility. American French Multiple Sclerosis Genetic Group. AB - Recently, genome-wide searches for multiple sclerosis (MS) susceptibility genes have suggested that the chromosome 17q22-q24 region might contain susceptibility genes in two sets of families of different ethnic backgrounds (Finnish and British). Therefore, we decided to test this region in two sets of families of different ethnic backgrounds (American and French), but collected according to the same diagnostic criteria. All lod-score values were non-significant. Moreover, we could exclude that the 17q22-24 region might contain a gene increasing the sibling recurrence risk of MS over 1.4, rendering the existence of such a gene very unlikely, at least in the group of tested families. PMID- 11196662 TI - Microsatellite alleles and single nucleotide polymorphisms (SNP) combine to form four major haplotype families at the human interleukin-10 (IL-10) locus. AB - Interleukin-10 (IL-10) is a pivotal immunoregulatory cytokine, influencing many aspects of the immune response. The IL-10 gene is located on chromosome 1 at 1q31 32 and is highly polymorphic. One microsatellite and three single nucleotide polymorphisms (SNPs) have been recorded within the 1.2 kb immediately upstream of the gene, with an additional microsatellite present at 4 kb upstream. The relationship between these two classes of polymorphism is poorly defined in the IL-10 gene. Haplotypes have been presented comprising alleles from the two microsatellite loci, and independently from the three SNPs, but these have not yet been brought together to define unified halpotypes. In the present report we describe the 29 IL-10 haplotypes found in 56 Dutch European families and show that they fall into four major haplotype groups, each of which spans the 4 kb upstream of the IL-10 gene and has a different distribution of IL10.G alleles. In addition, we describe three novel single nucleotide polymorphisms in the human IL 10 gene and suggest how they relate to these four haplotype families. PMID- 11196663 TI - Two polymorphisms within interleukin-3 (hIL3) gene detected by mismatch PCR/RFLP. AB - Two alleles of IL-3 have been reported to GenBank (GenBank M14743, M20137). The sequence difference between these two alleles is at the first nucleotide of the 27th codon (the 131st nucleotide from the initiation site): thymine and cytosine, and leading the amino acid difference: proline and serine (Pro27Ser). The other allelism, thymine and cytosine, was also observed at position -16 of the IL-3 upstream promotor region (GenBank L10616, M60870). We clarified that these substitutions were frequent polymorphisms in the Japanese population by using the mismatch-PCR (polymerase chain reaction)/RFLP (restriction fragment length polymorphism) method. PMID- 11196664 TI - A highly polymorphic CA repeat marker at the interleukin-11 locus. AB - The interleukin-11 (IL-11) stimulates T cell-dependent development of immunoglobulin-producing B cells and collaborates with IL-3 in supporting murine megakaryocyte colony formation. The interleukin-11 (IL-11) also stimulates osteoclast formation and inhibits osteoclast function in vitro and has been implicated in estrogen deficiency-induced bone loss. We isolated a polymorphic dinucleotide (CA) repeat sequence from a genomic clone containing the IL-11 gene located at 19q13.3-q13.4. High heterozygosity (0.81) makes this polymorphism a useful marker in genetic study of disorders affecting immune response and bone metabolism. PMID- 11196665 TI - Identification of novel single nucleotide polymorphisms in intron 1B and exon 1C of the human interleukin-1 receptor type I (IL-1RI) gene. AB - We have identified two novel single nucleotide polymorphisms in the 5' region of the human IL-1RI gene: (1) A-->G at position 52 in intron 1B (GenBank accession number AF146426), which creates an Mspl restriction endonuclease site. Allele frequencies in a Caucasian population were 0.1 (A allele) and 0.9 (G allele). (2) A-->T at position 140 in exon 1C (GenBank accession number AF146427). Allele frequencies in a Caucasian population were 0.27 (A allele) and 0.73 (T allele). PMID- 11196666 TI - A bi-allelic VNTR in the human TNFR2 (p75) gene promoter. AB - We describe a bi-allelic VNTR polymorphism within a 42 bp region in the promoter of the tumour necrosis factor receptor 2 gene (TNFR2). Within this region there are one (Allele 1) or two (Allele 2) repeats of a 15 bp sequence, 5'-GCCGGGC AGGTGGAG-3'. Allele frequencies observed in a Caucasian population were 0.3 (Allele 1) and 0.7 (Allele 2). PMID- 11196667 TI - A novel single nucleotide polymorphism and five probable haplotypes in the 5' flanking region of the IL-6 gene in African-Americans. AB - In order to identify novel single nucleotide polymorphisms (SNPs), we sequenced a 940 bp region of the 5' flanking region of the IL-6 gene in 63 normal African Americans. We identified a biallelic (G/C) SNP at position -573 relative to the transcription start site (-573C allele frequency 0.095). This SNP, together with SNPs at -598 and -174, allows identification of five probable haplotypes. Haplotypes containing the -174C allele, which has been associated with lower plasma IL-6 levels, were uncommon (4%). These haplotypes may influence IL-6 gene transcription and thus may contribute to racial differences in the prevalence of inflammatory diseases. PMID- 11196668 TI - Association of the TNF +489 polymorphism with susceptibility and radiographic damage in rheumatoid arthritis. AB - Multiple genetic factors contribute to susceptibility to rheumatoid arthritis (RA). The extent of variability in disease presentation in RA may be related to genetic heterogeneity. In this study we investigated the association of the TNF gene polymorphism at position +489 with susceptibility to and severity of RA. Analysis of the frequency of the +489 A and G alleles in a group of 293 consecutive RA patients and 138 healthy controls revealed a significant decrease of the A allele. The +489 GA patients had a 3.9 times decreased chance of having erosive disease than +489 GG patients. These results were confirmed in a prospective study using a cohort of 112 patients who were followed for 12 years. The progression rate of the erosion score over 12 years expressed as Sharp score for X-rays of hands and feet was 3.4 per year for the GA-genotyped patients and 12.1 for the GG-genotyped patients. These associations were independent of rheumatoid factor and HLA-shared epitope positivity. In conclusion, these data suggest that the intron TNF +489 polymorphism is associated with susceptibility to and disease severity of RA independently of HLA-shared epitope-positive alleles. PMID- 11196669 TI - New variations of human CC-chemokine receptors CCR3 and CCR4. AB - CCR3 and CCR4 are the members of CC chemokine receptor family expressed on Th2 type CD4+ T cells. In this study, variation screening of the entire coding regions of CCR3 and CCR4 was performed, and possible association with several autoimmune diseases was tested, using the genomic DNA from 304 Japanese healthy individuals and 272 Japanese patients with rheumatic diseases. One non-synonymous substitution was identified in CCR3 gene, whereas in CCR4 gene, two non synonymous and two synonymous substitutions were detected. Among the synonymous substitutions, CCR4 1014(C-->T) was observed in 7.2% of the healthy individuals and 6.6% of the patients, and was considered as a single nucleotide polymorphism. All other variations were observed in only one or two individuals. No significant association was observed between any of the variations and any of the rheumatic diseases. Among these variations, CCR3-C218S substitution coded by 652(T-->A) substitution was localized in the region conserved among the G protein coupled receptor family. Reactivity of eosinophils to the monoclonal antibody against CCR3 and the chemotaxis to eotaxin were slightly reduced in this patient as compared with healthy controls or a patient with Behcet disease homozygous for the common allele, while CCR3 mRNA level was not different. These findings suggest that CCR3-C218S substitution may lead to the reduced function of CCR3 at the protein level. Further study will be of interest to test whether CCR3-C218S variation or any of the CCR4 variations has a significant role in rendering susceptibility to immunological diseases or resistance to HIV infection. PMID- 11196670 TI - The major histocompatibility complex-encoded class I-like HFE abrogates endocytosis of transferrin receptor by inducing receptor phosphorylation. AB - The major histocompatibility complex-encoded gene, Hfe, has been implicated to play a pivotal role in hereditary hemochromatosis, a common autosomal recessive disorder of iron metabolism. The recent finding that a physical interaction between HFE and transferrin receptor establishes a functional link between HFE and transferrin receptor-mediated iron metabolism in the pathophysiology of hereditary hemochromatosis. To elucidate the underlying mechanisms by which HFE interacts with and affects transferrin receptor function, we have systematically investigated the consequences of the HFE-transferrin receptor interaction in cellular iron homeostasis. Herein we show that in HFE-expressing cells, the amount of intracellular transferrin is decreased by approximately 28%, despite a approximately 40% increase in surface-expressed transferrin receptor. Kinetic analysis of receptor-bound transferrin endocytosis reveals that HFE expression not only reduces transferrin binding but also abrogates transferrin receptor endocytosis. As a result, HFE expression leads to an accumulation of non functional transferrin receptors at the cell surface, and a decrease in iron uptake. Moreover, HFE expression induces hyper-serine phosphorylation of the transferrin receptor. Taken together, these results suggest that HFE negatively modulates cellular iron uptake by impairing transferrin receptor endocytosis via HFE-induced receptor phosphorylation. PMID- 11196671 TI - Interethnic studies of TNF polymorphisms confirm the likely presence of a second MHC susceptibility locus in ankylosing spondylitis. AB - The objective of this study was to investigate TNF promoter region polymorphisms for association with susceptibility to ankylosing spondylitis (AS). The TNF -238 and -308 polymorphisms were genotyped in 306 English AS cases and 204 ethnically matched healthy B27-positive controls, and 96 southern German AS cases, 58 B27 positive and 251 B27-negative ethnically matched controls. Additionally, the TNF 376 polymorphism was genotyped in the southern German cases and controls. In the southern German AS patients a significant reduction in TNF -308.2 alleles was seen, compared with B27 positive controls (odds ratio 0.4, P = 0.03, 95% confidence interval 0.2-0.9), but no difference in allele frequencies was observed at TNF -238. Significant association between AS and both TNF -238 and TNF -308 was excluded in the English cases. These results confirm previous observations in the southern German population of association between TNF promoter region polymorphisms and AS, but the lack of association in the English population suggests that these polymorphisms themselves are unlikely to be directly involved. More likely, a second, non-HLA-B, MHC locus is involved in susceptibility to AS in these two populations. PMID- 11196672 TI - Genetic influence on peripheral blood T lymphocyte levels. AB - T lymphocytes are a major component of the adaptive immune system. CD4 positive T cell subpopulations regulate B cell and macrophage effector function while CD8 positive T cells are largely responsible for anti-viral cytotoxic activity. The degree of natural variation in the levels and ratios of the various T cell subpopulations is a possible risk factor for the development of autoimmune disease, infectious disease and cancer. There is some evidence from studies of inbred strains of mice and humans which suggests that variation in T cell subpopulations is genetically influenced. However, family studies alone cannot distinguish between common environmental and shared genetic influences and provide less robust estimates of the heritability than twin studies. To comprehensively examine genetic influences on a selection of important T cell phenotypes, we investigated variation in levels of total lymphocytes, CD3+, CD4+, CD8+, CD3+CD4+, CD3+CD8+ lymphocytes and in CD4:CD8 ratio as a proportion of lymphocytes and of T cells using the classical twin model approach. Healthy female twin pairs were sampled from the St. Thomas' UK Adult Twin Registry. A maximum of 103 monozygotic (MZ) and 186 dizygotic (DZ) twins aged 18-80 years participated in the study. Whole blood samples were analysed for T cell subsets by flow cytometry. The relative genetic contribution to these phenotypes was estimated using a variance components model-fitting approach. Heritability estimates were calculated of 65% for CD4:CD8 T cell and lymphocyte ratios, around 50% for absolute lymphocyte, CD3+ and CD4+ counts, and 56% for CD8+ numbers. Unique (rather than shared) familial environment explains the remainder of the variance. Genetic factors have a major influence on the variation in peripheral T cell subset numbers. Polymorphism dictating such variation should be taken into account when assessing risk factors for T cell immune-mediated disease with a genetic background. PMID- 11196673 TI - New polymorphisms of human CD80 and CD86: lack of association with rheumatoid arthritis and systemic lupus erythematosus. AB - The crucial role of costimulatory molecules, CD28, CTLA-4, CD80 and CD86, for T cell activation and inhibition has been established. In the previous study, we reported the results of a polymorphism screening of human CTLA-4 gene. In this study, we screened for polymorphisms of human CD28, CD80 and CD86 genes, and detected that polymorphisms were tested for the association with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Variations were identified in the coding regions of CD80 (452G/A, 614C/G and 864A/G) and CD86 (1057A/G), while no variation was observed in the coding region of CD28. The variations at CD80 position 452 and CD86 position 1057 were present in a substantial proportion of the Japanese population, and were considered to be single nucleotide polymorphisms within the coding sequence (cSNPs). CD80 864 (G-->A) leads to the amino acid substitution N186D, and CD86 1057 (A-->G) results in A304T substitution. Furthermore, in the analysis of CD80 5'-flanking region, six SNPs, 454C/A, -387T/C, -232G/A, -79G/C, -7T/C and /A, and one insertion, -558ins (CATGA), were identified. The combination of these variations was found to constitute four promoter alleles of CD80. None of the observed variations was significantly associated with RA or SLE. Further studies will be of particular interest to examine the functional difference of the promoter alleles for the transcriptional activity of CD80, as well as the evolutionary pathway of the four alleles. PMID- 11196674 TI - Human genetic factors related to susceptibility to mild malaria in Gabon. AB - Several human genetic factors, including red blood cell polymorphisms (ABO blood group, sickle-cell trait, G6PD deficiency) as well as point mutations in the mannose binding protein (MBP) and in the promoter regions of both the TNF-alpha and NOS2 genes, influence the severity of disease due to infection with Plasmodium falciparum. We assessed their impact on mild P. falciparum malaria, as part of a longitudinal investigation of clinical, parasitological and immunological parameters in a cohort of 300 Gabonese schoolchildren. We found the following frequencies: blood group O (0.54), sickle-cell trait (0.23), G6PD deficiency (0.09), MBP gene mutations (0.34), TNF-alpha promoter mutations (at positions -238: 0.17 and -308: 0.22) and NOS2 promoter mutation (0.18). Blood group O or hemoglobin AA were associated with protection against higher parasitemia. Girls with normal G6PD enzyme activity were protected against clinical malaria attacks. In addition, we demonstrated for the first time that the mutation at position -238 of the gene coding for the promoter region of TNF alpha was positively correlated with the level of the antibody response specific for epitopes of the antigens MSA-2 and RAP-1 of P. falciparum. PMID- 11196675 TI - Cloning, expression and initial characterization of interleukin-19 (IL-19), a novel homologue of human interleukin-10 (IL-10). AB - Interleukin-10 (IL-10) is a pleiotropic cytokine with important immunoregulatory functions whose actions influence activities of many of the cell-types in the immune system. We report here identification and cloning of a gene and corresponding cDNAs encoding a novel homologue of IL-10, designated IL-19. IL-19 shares 21% amino acid identity with IL-10. The exon/intron structure of IL-19 is similar to that of the human IL-10 gene, comprising five exons and four introns within the coding region of the IL-19 cDNA. There are at least two distinct IL-19 mRNA species that differ in their 5'-sequences, suggesting the existence of an intron in the 5'-sequences of coding portion of the IL-19 gene. The longer 5' sequence contains an alternative initiating ATG codon that is in-frame with the rest of the coding sequence. The expression of IL-19 mRNA can be induced in monocytes by LPS-treatment. The appearance of IL-19 mRNA in LPS-stimulated monocytes was slightly delayed compared to expression of IL-10 mRNA: significant levels of IL-10 mRNA were detectable at 2 h post-stimulation, whereas IL-19 mRNA was not detectable until 4 h. Treatment of monocytes with IL-4 or IL-13 did not induce de novo expression of IL-19, but these cytokines did potentiate IL-19 gene expression in LPS-stimulated monocytes. In addition, GM-CSF was capable of directly inducing IL-19 gene expression in monocytes. IL-19 does not bind or signal through the canonical IL-10 receptor complex, suggesting existence of an IL-19 specific receptor complex, the identity of which remains to be discovered. PMID- 11196676 TI - Allele associations reveal four prominent haplotypes at the human interleukin-6 (IL-6) locus. AB - We have examined four polymorphic elements in the human interleukin-6 (IL-6) locus and described their allele distribution in 73 unrelated, healthy individuals from the West-of-Scotland. These comprised three single nucleotide polymorphisms (SNP) in the 5' promoter region of the gene and one VNTR in the 3' region of IL-6. A statistical consideration of the relationship between alleles at each locus was carried out. Of a total of 12 possible haplotypes observed in the population, the analysis suggested that four were prominent. These accounted for 41.1%, 28.1%, 14.4% and 3.4% respectively; in total, 87% of the haplotypes present. Frequently, these proposed haplotypes were supported by homozygosity across all four loci within individuals. We propose that these haplotypes be identified as IL6.0103, IL6.0204, IL6.0207 and IL6.0307, in recognition of their frequency in this population and the alleles that they contain. PMID- 11196677 TI - Linkage analysis of a candidate region in Scandinavian sib pairs with multiple sclerosis reveals linkage to chromosome 17q. AB - To date, four genome screens have been completed in the demyelinating autoimmune disease multiple sclerosis (MS). Although these screens failed to identify any loci with major effects on susceptibility, several novel regions of potential linkage were suggested, including the long arm of chromosome 17. In order to further pursue this promising region we have investigated six highly polymorphic microsatellite markers in 115 Scandinavian families with MS affected sib pairs. Multipoint linkage analysis revealed a peak maximum likelihood score (MLS) of 0.9 in the region of marker D17S787. Stratifying the results on the basis of HLA-DR2 status showed that the linkage was not limited to families segregating for the HLA-DR2 allele as has previously been suggested. In conclusion, our results further support the proposal that a multiple sclerosis susceptibility locus is contained on chromosome 17q. PMID- 11196678 TI - High-resolution analysis of IL-6 minisatellite polymorphism in Sardinian multiple sclerosis: effect on course and onset of disease. AB - A minisatellite polymorphism located in the 3' flanking region of the interleukin 6 (IL-6) gene was analysed in 192 Sardinian simplex families with multiple sclerosis (MS). By applying a high-resolution sizing approach, 9 alleles were identified. None of these were associated with in globo susceptibility to MS as shown by transmission disequilibrium testing. Analysis of clinically different groups showed that the A5 allele was associated with a benign (P = 0.007) but not with a malignant (P = 0.45) course of disease. In particular, the frequency of the A5/A5 genotype was significantly higher in patients with benign MS (P = 0.002). In addition, carriage of any of the larger alleles (A6-->A9) was associated with accelerated onset of disease (P = 0.025). Our results suggest that allelic variations in the IL-6 gene may predispose to alterations in the course and initial onset of MS. PMID- 11196679 TI - Mannose binding lectin (MBL) gene mutation is not a risk factor for systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in Japanese. AB - Mannose binding lectin (MBL) deficiency may be associated with increased susceptibility to infection and autoimmune disorders, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In the present study, we performed for the first systematic search for mutations in all the four exons of the MBL gene using polymerase chain reaction (PCR)/single-strand conformation polymorphism (SSCP) analysis. Of 49 healthy Japanese individuals studied, only the previously reported mutation at the codon 54 (substitution from Gly to Asp; G54D) was identified. The allele frequencies of G54D in 105 healthy Japanese individuals, 95 SLE patients and 59 RA patients, were 0.233, 0.226 and 0.178, respectively, which were not significantly different. In addition, two polymorphisms at positions of -550 and -221 in the promoter region were not associated with SLE and RA. It is unlikely that MBL deficiency plays a major role in the pathogenesis of SLE and RA in Japanese. PMID- 11196680 TI - Independent contribution of HLA-DRB1 and TNF alpha promoter polymorphisms to the susceptibility to Crohn's disease. AB - Although a number of studies reported the association of HLA-DRB1 and Crohn's disease (CD), the actual alleles associated with CD are considerably variable among populations. On the other hand, the relevance of tumor necrosis factor alpha (TNF alpha) in the pathogenesis of CD is established through experimental as well as clinical studies, raising the possibility that TNFA polymorphism is primarily or independently contribute to the association of HLA region genes with CD. New polymorphisms which may affect the transcriptional activity were recently reported within the upstream promoter region of TNFA gene. In the present study, we compared HLA-DRB1, TNFA promoter and TNF receptor 2 (TNFR2) genotypes in 154 Japanese patients with CD and 265 unrelated healthy controls to evaluate the individual contribution of these genes to the genetic predisposition to CD. Significant positive association was observed in HLA-DRB1*0405 (P = 0.001, odds ratio (OR) = 2.02) and 0410 (P = 0.002, OR = 4.79). Among the TNFA promoter haplotypes, TNFA-U03 (-1031C, -863A, -857C) was significantly increased (P = 0.008, OR = 1.64), while TNFA-U04 (-1031C, -863C, -857C) was significantly decreased (P = 0.014, OR = 0.12), in CD. The association with TNFA-U03 was independent of that with DRB1*0405 and 0410, and apparent additive or multiplicative effect was not observed between these susceptibility alleles. No association was observed between TNFR2-196M/R polymorphism and CD. These results indicated that both of HLA-DRB1 and TNFA promoter polymorphisms contribute to the susceptibility to CD in an independent manner. PMID- 11196681 TI - Evidence for recent selection of the CCR5-delta 32 deletion from differences in its frequency between Ashkenazi and Sephardi Jews. AB - Recent studies have shown higher frequencies of the CCR5-delta 32 allele and the CCR5-delta 32/delta 32 genotype, which confers protection against HIV infection, in northern Europe as compared to Mediterranean countries. Here, we analyse the prevalence of CCR5-delta 32 in 922 HIV seronegative blood donors in Israel to verify its frequency in Jews of Ashkenazi and Sephardi origin. A significant difference (P < 0.001) was found between the CCR5-delta 32 allele frequency in Ashkenazi (13.8%) vs (4.9%) Jews. In contrast, no significant difference was observed in the frequency of the CCR2-641 mutation between Ashkenazi (9.2%) and Sephardi (13.4%) Jews. Using the Island model we calculate that a minimal genetic migration rate of 3% per generation would have been necessary if the higher CCR5 delta 32 prevalence in Ashkenazi is to be fully explained by mixing with the indigenous north-European populations. This putative migration rate is 20-fold higher than that currently estimated from other genes, and would correspond to a non-realistic minimal current admixture of 80%. Thus, our results suggest that a positive selection process for CCR5-delta 32 should have occurred in northern Europe at most a 1000 years ago, after the Ashkenazi Jews separated from their Sephardi kin and moved to north Europe. PMID- 11196682 TI - No evidence for linkage in the promoter region of the inducible nitric oxide synthase gene (NOS2) in a Danish type 1 diabetes population. AB - Exposure of human pancreatic islets to a mixture of cytokines induces expression of inducible nitric oxide synthase (iNOS), impairs beta-cell function and induces apoptosis. Exposing human islets to high amounts of NO from chemical NO-donors causes DNA strand breaks and mitochondrial damage, suggesting that NO is deleterious to human beta-cells. Hence, we consider the gene encoding iNOS in beta-cells, NOS2, a candidate gene for type 1 diabetes in humans. In the present study we have tested three identified polymorphisms within the promoter sequence of the human NOS2 gene in a type 1 diabetic family material comprising 154 affected sib-pair families and 103 affected simplex families (1143 individuals in total). PCR-based amplification of the polymorphic loci were established. Linkage analysis was performed using the extended transmission disequilibrium testing (ETDT). A Bsal RFLP was found not to be polymorphic in 20 type 1 diabetic patients and 14 healthy control subjects and was not analysed further. In affected cases a nine allele CCTTT repeat and a bi-allelic TAAA repeat revealed allelewise Petdt of 0.52 and 0.60, respectively. ETDT applied to (TAAA)n; (CCTTT)n haplotypes demonstrated random transmission from heterozygous parents to affected offspring. In conclusion, the tested polymorphisms within the NOS2 gene promoter did not show evidence for linkage to type 1 diabetes in a Danish family material. PMID- 11196683 TI - Lack of association between the polymorphism at the heat-shock protein (HSP70-2) gene and systemic lupus erythematosus (SLE) in the Mexican mestizo population. AB - Major histocompatibility complex (MHC) alleles have been recognized as genetic factors for developing systemic lupus erythematosus (SLE). In the present study we analyzed whether a heat-shock protein gene (HSP70-2) is involved in determining susceptibility to develop SLE in a Mexican Mestizo population. A HSP70-2 Pst I polymorphism was detected by a restriction fragment length polymorphism analysis of polymerase chain reaction (PCR-RFLP) in 107 SLE patients and 158 healthy controls. No statistically significant differences were observed in the HSP70-2 allele distribution between patients and healthy controls. HLA-DR analysis showed an increased frequency of HLA-DR3 allele in the patients group (P < 0.05, OR = 2.26, EF = 6.0%). On the other hand, when we analyzed HSP70-2 polymorphism in relation to HLA-DR3 allele, we could only detect an increased frequency of AB genotype in the DR3 negative patients (pC < 0.05, RR = 2.6, EF = 11.3%). Linkage disequilibrium was observed for three haplotypes: HLA-DR3-HSP70 2A (D = 0.03, D' = 0.67, P < 0.01); HLA-DR1-HSP70-2A (D = 0.03, D' = 0.86, P < 0.01) and HLA-DR8-HSP70-2B (D = 0.02, D' = 0.46, P = 0.02). Our data indicate that HSP70-2 gene polymorphism as opposed to the other ethnic groups does not appear to be relevant in SLE susceptibility in Mexican patients and that the distribution of the different alleles depend on the frequency of HLA alleles associated with them. PMID- 11196684 TI - P-glycoprotein (encoded by multidrug resistance genes) is not required for interleukin-2 secretion in mice and humans. AB - P-glycoprotein (encoded by multidrug resistance genes), a member of the ATP binding cassette transporter protein superfamily, has been shown to play a role in the secretion of cytokines. This conclusion was based upon the inhibition of cytokine secretion by anti-P-gp monoclonal antibodies. In this study, we show that anti-CD3-stimulated lymphocytes from wild-type, mdr1a knock out and mdr1ab double knock out mice produce similar amounts of IL-2, IFN-gamma, IL-4, and IL 10. In addition, Jurkat T cells that lack P-gp and MDR1-transfected Jurkat T cells (JurkatP-gp) as well as purified human peripheral blood CD4+ P-gp+ and CD4+ P-gp- and CD8+ P-gp+ and CD8+ P-gp- T cell subsets produced comparable amounts of IL-2. These data show that P-gp is not required for secretion of IL-2, IFN-gamma, IL-4, and IL-10 secretion in mice and IL-2 secretion in humans. PMID- 11196685 TI - Association analysis with microsatellite and SNP markers does not support the involvement of BCL-2 in systemic lupus erythematosus in Mexican and Swedish patients and their families. AB - We have described suggestive linkage between microsatellite markers within the cytogenetic region 18q21-23 and SLE, a region where linkage with other autoimmune diseases has also been detected. The Bcl-2 gene located within this region, is a candidate gene because of its role in apoptosis, a physiological mechanism that could be deregulated in autoimmune disease. Furthermore, several studies have found abnormalities of Bcl-2 expression in SLE patients. We therefore sought to determine if the Bcl-2 gene is involved in SLE by studying members of a large cohort of Mexican SLE patients (n = 378) and 112 Swedish simplex families. Using a microsatellite marker and two single nucleotide polymorphisms located within the gene, we were unable to detect association between Bcl-2 and SLE in either population. We also tested whether combinations of alleles of the Bcl-2 and IL 10.G microsatellites would increase the risk for SLE. Our results do not support such hypothesis. Our findings suggest that linkage between SLE and the 18q21-23 region is due to a gene other than Bcl-2. PMID- 11196686 TI - Tumor necrosis factor gene polymorphisms in patients with cirrhosis from chronic hepatitis C virus infection. AB - Pro-inflammatory cytokines including tumour necrosis factor (TNF) mediate the pathogenesis of hepatitis C virus (HCV) infection. The distribution of TNF gene polymorphisms was examined among cirrhotic and non-cirrhotic patients infected with HCV. Thirty Caucasians with cirrhosis due to chronic HCV infection and 114 HCV-infected patients histopathologically free of cirrhosis were genotyped for genetic variants in TNF, lymphotoxin alpha and TNF-receptor type I using PCR based techniques. Variability in the progression of HCV-related cirrhosis was assessed in a multivariate model including genetic and non-genetic factors such as gender, estimated duration of infection, alcohol consumption, and viral genotype. Viral genotype and non-genetic host features were not independently related to the occurrence or rate of development of cirrhosis in the patient population. In contrast, the TNF promoter variants TNF2 (-238A) and TNF3 (-308A) conferred a 3.2-fold and 5.1-fold risk of cirrhosis respectively (P = 0.03 for both). Reciprocal effects were observed with several TNF alleles and haplotypes defined by the -238G/A and -308G/A dimorphic sequences. Polymorphisms in the TNF alpha promoter appear to be associated with variability in the histological severity of chronic hepatitis C infection. PMID- 11196687 TI - Spatial, a gene expressed in thymic stromal cells, depends on three-dimensional thymus organization for its expression. AB - Although the importance of thymic stroma in thymopoiesis has been recognized, the underlying molecular details regarding stromal cell biology remain obscure. To study this area, we have cloned genes expressed in thymic stromal cells. Spatial is alternatively spliced to generate two mRNAs in thymus and lymph node (LN) but it is not expressed in the spleen. In mouse embryos, the short form begins expression at day 10 while the long form is not detected until day 12. Both mRNAs encode proline rich proteins and their closest homology is to homeobox and POU domain transcription factors. Spatial is not expressed in thymocytes, but it is expressed in 2-deoxyguanosine-treated day 14 fetal thymic organ culture (FTOC) and in reaggregated FTOC. These data suggest that a normal three-dimensional organization of stromal cells is required for Spatial expression. An antiserum raised against a C-terminal peptide detected proteins of 38 and 32 kDa in Western blots of total thymus proteins. In frozen thymus sections, subcapsular epithelial cells were stained with the anti-Spatial antiserum. Paracortical subcapsular cells of unknown function were also stained in the LN. Both forms of Spatial fused to the green fluorescent protein (GFP) localize to the nucleus in transfected cells. PMID- 11196688 TI - Dinucleotide repeat polymorphism in the interleukin-10 gene promoter (IL-10.G) and genetic susceptibility to early-onset periodontal disease. AB - Emerging evidence suggests that certain genetic polymorphisms are associated with various sub-groups of early-onset periodontal diseases (EOP). We determined the genotype with respect to a (CA)n dinucleotide repeat polymorphism in the promoter region of the interleukin-10 gene (IL-10.G) in 72 patients with EOP and in 73 healthy individuals in order to test for possible disease associations. Some differences between the frequency of individual IL.10.G alleles in the patients groups as compared to the healthy controls were detected. For example the frequency of the IL-10.G9 allele in a clinical sub-group of the EOP patients with localised disease (L-EOP, n = 21) was 64.3% as compared to 41.8% in the controls. However, statistical analysis (Monte Carlo simulation) revealed that the differences in IL-10.G allele distribution between the healthy controls and both the EOP group and the L-EOP group were not statistically significant. We conclude that this study provides no evidence for a role of IL-10.G alleles in genetic susceptibility to EOP. PMID- 11196689 TI - The common functional C(-159)T polymorphism within the promoter region of the lipopolysaccharide receptor CD14 is not associated with sepsis development or mortality. AB - Sepsis is characterised by a systemic inflammatory response to bacterial products during infection, which interestingly both in humans and animal models is gender associated with a higher susceptibility of males than females. The CD14 receptor is involved in activation of cells by lipopolysaccharides released from Gram negative bacteria and, as recently shown, also by products of Gram-positive bacteria (e.g., peptidoglycans and lipoteichoic acid). The functional relevance of a C(-159)T CD14 polymorphism recently has been shown based on correlation of the T allele to higher plasma levels of soluble CD14, and higher membrane expression on monocytes. We, therefore, now analysed this CD14 polymorphism in 204 patients with severe sepsis and 247 controls. No significant difference of allele frequencies was observed between sepsis patients and controls neither for males nor females. Mortality also was not associated with the polymorphism studied. This may suggest that other mechanisms for lipopolysaccharide recognition, such as the recently described Toll-like receptors are important for inflammatory cell activation in sepsis. PMID- 11196690 TI - Immuno- and genetic therapy in autoimmune diseases. AB - Animal models of autoimmune disease have been developed that mimic some aspects of the pathophysiology of human disease. These models have increased our understanding of possible mechanisms of pathogenesis at the molecular and cellular level and have been important in the testing, development and validation of new immunotherapies. The susceptibility to develop disease in the majority of these models is polygenic as is the case in humans. The exceptions to this rule are gene knock outs and transgenic models of particular genes which, in particular genetic backgrounds, have also contributed to the understanding of single gene function and their possible contribution to pathogenesis. Gene therapy approaches that target immune functions are being developed with encouraging results, despite the polygenic nature of these diseases. Basically this novel immuno-genetic therapy harnesses the knowledge of immunology with the myriad of biotechnological breakthroughs in vector design and delivery. Autoimmune disease is the result of genetic dysregulation which could be controlled by gene therapy. Here we summarize the genetic basis of these human diseases as well as some of the best characterized murine models. We discuss the strategies for their treatment using immuno- and gene therapy. PMID- 11196691 TI - Targeting the mucosa: genetically engineered vaccines and mucosal immune responses. AB - The discovery that inoculation of DNA leads to strong and long lasting immune responses generated enthusiasm to assess the efficacy of various genetically engineered vaccines against mucosally acquired infections. Various techniques have been used to generate the most suitable DNA vaccines, ranging from immunization with naked DNA to utilizing genetically engineered recombinant viruses and bacteria to deliver the DNA. Different DNA vaccine modalities and mucosal immune responses to them have been discussed. It has been shown that even though intramuscular and intradermal immunization with these vaccines generates strong systemic responses, mucosal responses are not induced. It has been proposed that the site of immunization determines mucosal immune responses and that primed lymphocytes preferentially accumulate at sites where they have been induced thus generating the strongest cellular and antibody responses at the site of vaccination. The impact of the site of induction on mucosal immune responses to vaccines is discussed. It is possible to enhance desired vaccine effects in the mucosa and to modify the undesirable side effects. Cytokines such as IL-2, IL 12, IL-15 and IL-18 have been used to enhance CTL activity while IL-5, IL-6 and the chemokine MIP-1 alpha have shown the capacity to increase IgA responses to vaccines. PMID- 11196692 TI - The new genetics of bone marrow transplantation. AB - There is now little doubt that functional immune polymorphism exists and can exert a significant effect on the severity of immunologic disease. Studies in this area are driven by the belief that an understanding of the influence of immune polymorphism on immunologic disease will improve our ability to predict disease occurrence and severity. The usefulness of this information is necessarily limited, however, by the fact that an individual has a fixed genome. If an individual has an allele which predisposes to increased disease severity, there is little we can do, other than treat the disease in that individual in a more aggressive manner or attempt to find preventative therapies. There is, however, one unique immunologic disorder that is an exception to this rule. Graft versus-host disease (GVHD), the major complication of bone marrow transplantation, is an immunologic reaction mediated, in large part, by donor T cells. It is unique in that it is the only immunologic disorder in which we can choose the genetics of the immune system causing the disorder. In this disease, more than any other, an understanding of the role of immune polymorphism is essential since we could hypothetically use this information to choose a donor whose T cells will not mediate GVHD of life-threatening severity. In this review, I argue that there is highly suggestive evidence that allelic polymorphism in non MHC genes encoding mediators of the immune response exerts a very significant effect on the severity of GVHD and that typing for such allelic polymorphisms will in future be as important as MHC-typing in choosing an appropriate donor for bone marrow transplantation. PMID- 11196693 TI - Interleukin-10 gene promoter polymorphism in English and Polish healthy controls. Polymerase chain reaction haplotyping using 3' mismatches in forward and reverse primers. AB - A polymerase chain reaction with sequence-specific primers (PCR-SSP) system using primers with mismatches at the 3' ends was developed to determine polymorphisms in IL-10 promoter region. Three previously described biallelic polymorphisms in IL-10 were linked in a 12 reaction PCR-SSP system and the method used to provide genotype data on 233 UK and 166 Polish controls. There are eight possible polymorphic combinations in IL-10 promoter gene but only three were observed in both control groups. Population frequencies of IL-10 genotypes show, in contrast to HLA, that UK and Polish frequencies are remarkably similar. PMID- 11196694 TI - Identification of complement receptor one (CR1) polymorphisms in west Africa. AB - Complement receptor one (CR1) is a ligand for the rosetting of Plasmodium falciparum infected red cells with uninfected cells. Since CR1 exhibits three known polymorphisms, we studied European-Americans (n = 112) and African Americans (n = 330) and Malians (n = 158) to determine if genetic differences existed in an area endemic for malaria that could offer a survival advantage. The frequencies of Knops blood group phenotypes McC(b+) and Sl(a-) were greatly increased in Africans vs Europeans. Although the frequency of McC(b+) was similar between Africans from the USA or Mali, the Sl(a-) phenotype was significantly higher in Mali (39% vs 65%, respectively). There was an increased frequency of the largest size (250 kD) of CR1 in Mali, but this did not differ significantly from the USA (P = 0.09). Both cohorts of Africans had higher expression of red cell CR1 than European-Americans but this showed little difference between the USA and Mali groups. Thus, the most important CR1 polymorphism relevant to rosetting of malaria infected cells appears to be the Knops blood group. PMID- 11196695 TI - Single nucleotide polymorphisms in the coding regions of human CXC-chemokine receptors CXCR1, CXCR2 and CXCR3. AB - Chemokines and their receptors have critical roles in inflammatory and immunological responses, and thus their genetic contribution to various human disorders needs investigation. In this study, systematic variation screening of the entire coding regions of CXCR1 (IL8RA), CXCR2 (IL8RB) and CXCR3 was carried out, using genomic DNA from a large number of Japanese healthy individuals and patients with rheumatic diseases. In addition to the previously reported variations in CXCR1 and in CXCR2, two non-synonymous, two synonymous substitutions and one nonsense mutation of CXCR1, one non-synonymous and two synonymous substitutions of CXCR2, two non-synonymous substitutions of CXCR3 were newly identified. The common single nucleotide polymorphisms (SNPs) at CXCR1 codon 827 and CXCR2 codon 786 were in strong linkage disequilibrium. In addition, familial analysis indicated that human CXCR3 is located on chromosome X. No significant association was observed between the variations and the tested rheumatic diseases. However, CXCR variations identified in this study will provide valuable information for the future studies in medical sciences as well as in human genetics. PMID- 11196696 TI - IL-6 promoter polymorphisms in rheumatoid arthritis. AB - We investigated the possible association between the IL-6 promoter polymorphisms, at positions -622 and -174, and susceptiblity to, and/or outcome of, rheumatoid arthritis (RA). A total of 163 patients with RA and 157 healthy controls were genotyped for IL-6 using a PCR-RFLP method. The -622 and -174 alleles were in complete linkage disequilibrium. No difference was observed in the distribution of IL-6 promoter genotype or allele frequencies between RA patients and controls. However, a significant difference in the mean age at disease onset between IL-6 genotypes was observed. The present data appear to rule out an important role of IL-6 promoter polymorphisms in the susceptibility to RA. However, IL-6 genotypes may contribute to the pathogenesis of the disease by influencing the age at disease onset. PMID- 11196697 TI - Identification of four novel interleukin-13 gene polymorphisms. AB - The development of allergic asthma is thought to involve environmental and inherited genetic components and has pathophysiological features reflecting in part the activity of T cell cytokines. Interleukin-13, a product primarily of activated lymphocytes, is considered to be a critical effector molecule in allergic airway response and has been found to be overexpressed in the airways of patients with asthma. The IL-13 gene is located on chromosome 5q31, one of the major loci to be linked to asthma susceptibility, and amongst a cluster of genes which dominate the immunopathology of allergic disease. Recently, an IL-13 promoter polymorphism was found to be associated with allergic asthma. In the present study we report the identification of four novel biallelic polymorphisms in the IL-13 gene, two intronic and two exonic, one of which results in a basic to hydrophilic amino acid change. We characterised the frequencies of these four biallelic polymorphisms and the frequencies of the haplotypes, resulting from the combination of these four biallelic polymorphisms, in a population of 196 UK Caucasoid healthy individuals. PMID- 11196698 TI - Polymorphisms in the MBL2 promoter correlated with risk of HIV-1 vertical transmission and AIDS progression. AB - We investigated the polymorphisms of the promoter region of the MBL2 gene, which codifies for the Mannose-binding protein (MBP). The study population included 90 children with vertically acquired HIV-infection, further divided on the basis of the disease rate, 27 HIV exposed-uninfected children, and 74 healthy control subjects matched for ethnic origin to evaluate the MBP involvement in the risk of HIV-1 infection and to assess the role of the MBP promoter in AIDS progression. A region of 380 bp in the promoter of the MBL2 gene was analysed by PCR and direct sequencing of both DNA strands. We found that the polymorphism at position -550 influences the risk of HIV-infection and AIDS progression. Also a 6 bp deletion at position -328 was correlated with HIV-1 infection. This study indicates that the promoter of the MBL2 gene influences vertical transmission of HIV and the course of perinatal infection. PMID- 11196699 TI - A novel PCR-RFLP assay for the detection of a polymorphism in the 3' of STAT6 gene. AB - We have identified a novel single nucleotide polymorphism at position 2964 (G/A) in the 3' untranslated region of the human STAT6 gene (GeneBank Accession No. U16031). A novel PCR-RFLP method has been devised for this polymorphism using the amplification-created restriction site (ACRS) method. Allele frequencies in the UK Caucasian population were found to be 0.33 for allele A and 0.67 for allele G. PMID- 11196700 TI - Ku autoantigen (DNA helicase) is required for interleukins-13/-4-induction of 15 lipoxygenase-1 gene expression in human epithelial cells. AB - As reported previously in human monocytes, a human lung epithelial cell line, A549, showed de novo induction of 15-Lipoxygenase-1 (15-LO-1) in response to interleukins-13 (IL-13) and -4 (IL-4). In this cell line, 15-LO-1 expression, by RT-PCR and western blotting, was observed following 6 and 24 h of exposure to human IL-13 (ED50 5 ng/ml) and IL-4 (ED50 0.2 ng/ml). We have previously shown that no cis-acting regulatory elements exist within the 15-LO-1 promoter region. To define IL-13 and IL-4 responsive trans-acting elements, we identified a region (DP2: -353 to -304 bp site) within the 15-LO-1 promoter (by footprinting experiments) to which IL-13-responsive elements (or factors) bind specifically (Kelavkar et al, 1998, Mol Biol Rep 25, 173-182). To further delineate this region, we constructed (by site-directed mutagenesis) several deletion mutants in the 'LOPB5' region containing the 29 bp within the -353 to -304 bp of the DP2 core element. These were: DP3 (site totally deleted), DP4 (5 bp deleted at the center of the site), DP5 (8 bp at the 5'-end of the site) and DP6 (13 bp at the 3'-end of the site). Cotransfection of these deletion constructs (driving luciferase reporter genes) was associated with 90% (DP4, DP5 and DP6) or 100% (DP3) abrogation of promoter activity at 24 h. Purification of nuclear protein extracts from IL-13 and IL-4-stimulated A549 cells, using a DP2 core containing affinity column, identified a 150 kDa protein under non-denaturing conditions, and two, 70 and 85 kDa proteins under denaturing conditions. These were not detectable by Coomassie blue staining in control nuclear protein extracts. Matrix assisted laser desorption ionization mass spectrometry (MALDI-MS) of the tryptic digests of these proteins, identified one as the 86 kDA Lupus KU autoantigen protein P86 and the second as the 70 kDa Lupus KU autoantigen protein P70. Gel shift and supershift experiments using monoclonal antibodies toward Ku antigen and its individual subunits, and utilizing DP2 and other mutant oligonucleotides with purified nuclear protein extracts from control and cytokine-treated A549 cells, confirmed our findings. Furthermore, electroporation of neutralizing anti Ku70, Ku 80 and Ku70/80 antibodies into A549 cells totally suppressed IL-13 and IL-4-stimulated 15-LO-1 induction in these cells. Further, immunoprecipitation experiments data suggests that IL-4 and IL-13 activate Ku antigens and 15-LO-1 expression through distinct signaling events. In summary, in A549 cells, Ku antigen is induced in response to the cytokines, IL-13 and -4, and a 29 bp region within the -353 to -304 bp region of the 15-LO-1 promoter is required for its binding and subsequent induction of 15-LO-1 gene expression. The findings may provide an important link between the established dysregulated function of Ku antigen in auto-immune diseases, such as systemic lupus erythematosus and thyroiditis, and the increasingly recognized 'anti-inflammatory' role of 15-LO-1. PMID- 11196701 TI - Genetic control of susceptibility to UV-induced immunosuppression by interacting quantitative trait loci. AB - Ultraviolet B radiation (290-320 nm) initiates a dose and wavelength dependent down-regulation of cell-mediated immunity which is critical in experimental ultraviolet radiation (UV) carcinogenesis, preventing immune attack on highly antigenic UV-induced tumors. UV-induced immunosuppression has been demonstrated in humans and may be a risk factor for skin cancer. In this study, we have investigated genetic linkage of the autosomal loci controlling this trait. Previously, we had derived a model describing control of susceptibility to UV induced immunosuppression in inbred mice by unlinked interacting autosomal and X linked loci. A genome-wide scan using MIT microsatellite markers was carried out on 100 backcross (BALB/c x (BALB/c x C57BL/6) F1) mice derived from the inbred strains BALB/c (low susceptibility) and C57BL/6 (high susceptibility) and tested for systemic UV-induced immunosuppression of a contact hypersensitivity response. The values for % suppression for each animal and the genotype data were used to investigate genetic linkage by multiple regression analysis. Significance was assessed using the permutation test. Both main effects and interactive effects were investigated, first with each genotype marker singly, and secondly, in a novel approach using markers pairwise. A joint model was derived in which all loci and pairs of loci identified were included simultaneously in a multiple regression model. This model indicates four quantitative trait loci (QTLs) with significant main effects, one on chromosome 10 which decreased susceptibility to UV-induced immunosuppression and QTLs on chromosomes 6, 17 and 1 which increased susceptibility. Additionally, loci on chromosomes 14 and 19 showed significant interaction with the locus on chromosome 1. Further investigation indicated a potential three-way interaction involving the loci on chromosomes 1, 14 and 19. PMID- 11196702 TI - Linkage of human tumor necrosis factor-alpha to human osteoporosis by sib pair analysis. AB - Osteoporosis as well as osteopenia are common human conditions considered to result from the interplay of multiple genetic and environmental factors. Twin and family studies have yielded strong correlation between measures of bone mass and a number of genetic factors. Certain genes (e.g., cytokines such as interleukin 1, interleukin-6, or tumor necrosis factor-alpha) are capable of regulating metabolism, formation, and resorption of bone; all processes that determine bone mass. We tested 192 sib-pairs of adult Japanese women from 136 families for genetic linkage between osteoporosis and osteopenia phenotypes and allelic variants at the tumor necrosis factor-alpha (TNFA) locus, using a dinucleotide repeat polymorphism located near the gene. The TNFA locus showed evidence for linkage to osteoporosis, with mean allele sharing of 0.478 (P = 0.30) in discordant pairs and 0.637 (P = 0.001) in concordant affected pairs. Linkage with osteopenia was also significant in concordant affected pairs (P = 0.017). Analyses limited to the post-menopausal women in our cohort showed similar or even stronger linkage for both phenotypes. The results provide evidence that genetic variations within the TNFA locus or adjacent genes affect regulation of mineral metabolism in bone and some of them confer risk for osteoporosis in adult women. PMID- 11196703 TI - Characterization and genomic sequence of the murine 60 kD Ro gene. AB - Autoantibodies binding 60 kD Ro (or SS-A) are commonly found in patients with systemic lupus erythematosus and Sjogren's syndrome. While many studies have examined the autoimmune response directed against this RNA-protein, its function is still uncertain. As part of a broad effort to better understand animal models of anti-Ro autoimmunity we have characterized the murine 60 kD Ro gene. Southern blot analysis of mouse genomic DNA suggests that the 60 kD Ro gene is a single copy gene. The complete sequence of the gene was determined from three overlapping genomic lambda phage clones (GenBank accession number AF065398). The murine 60 kD Ro gene spans approximately 23 kb and consists of 8 or 9 exons. DNA sequence analysis revealed the presence of multiple B1 repetitive units. It maps in synteny with the human 60 kD Ro gene. Therefore, the isolation and characterization of the 60 kD Ro gene will be instrumental for future studies on protein function and the role this protein plays in the development of autoimmune responses. PMID- 11196704 TI - TNF-alpha-induced apoptosis in neonatal lymphocytes: TNFRp55 expression and downstream pathways of apoptosis. AB - Previously we have shown decreased Fas-mediated apoptosis in cord blood lymphocyte subsets. In this study, we compared tumor necrosis factor (TNF)-alpha induced apoptosis in T lymphocytes and their subsets between cord blood and peripheral blood from healthy young controls. The expression of TNF receptor I (TNFR-I) was assessed by flow cytometry and quantitative RT-PCR. The expression of adapter molecules TNF receptor-associated death domain (TRADD), Fas-associated death domain (FADD) and TNF-associated factor-2 (TRAF-2) and caspase 3 was analyzed by Western blotting. The activity of caspase 3 and caspase 8 was measured by colorimetric assay. The susceptibility of CD4+ and CD8+ T cells to TNF-alpha-induced apoptosis was measured by terminal deoxytidyl transferase mediated dUTP nick end labelling (TUNEL) assay. Both CD4+ and CD8+ T cell subsets from cord blood demonstrated decreased susceptibility to TNF-alpha-induced apoptosis that was associated with decreased activation of both caspase 8 and caspase 3 as compared to T cell subsets in peripheral blood. Furthermore, expression of TNFR-I, TRADD and caspase 3 was decreased in cord blood lymphocytes as compared to peripheral blood lymphocytes. The significance of these observations is discussed. PMID- 11196705 TI - The centromeric part of the human NK gene complex: linkage of LOX-1 and LY49L with the CD94/NKG2 region. AB - The natural killer (NK) gene complex is a genomic region containing lectin-type receptor genes. We have established a contig of PAC and BAC clones comprising about 1 Mb of the centromeric part of the NK gene complex. This region extends from the LOX-1 gene, which encodes a receptor for oxidized LDL and was found within 100 kb telomeric of the STS marker D12S77, contains the CD94 and NKG2 NK receptor genes and reaches beyond D12S852 on the proximal side. In this part we have mapped the human LY49L gene, a homologue of the rodent Ly49 genes, which encode important MHC class I receptors for the regulation of NK cell activity in rodents. The LY49L gene is localized 100 to 200 kb centromeric of the NKG2 gene cluster and 300 to 400 kb telomeric of the STS marker D12S841. Genomic sequencing of the complete gene including promoter and intron sequences confirmed that the structure is similar to the mouse Ly49 genes. Screening of several cDNA libraries did not detect any transcripts of putative additional human LY49 genes. In addition, in the course of these studies several EST sequences were localized in the region, one immediately upstream of the LY49L gene. PMID- 11196706 TI - CCR5 (chemokine receptor-5) DNA-polymorphism influences the severity of rheumatoid arthritis. AB - Chemokines are critical for the inflammatory process in autoimmune diseases such as rheumatoid arthritis (RA). The chemokine receptor-5 (CCR5) mediates chemotaxis by CC-chemokines and is expressed by lymphocytes with the Th1 phenotype and monocyte/macrophages. A 32 bp deletion in the CCR5 (CCR5-delta 32 allele) abolishes receptor expression in homozygotes, while CCR5-delta 32 carriers would express less receptor than wild-type homozygotes. This polymorphism is related to the resistance to HIV-1 infection and progression towards AIDS. We hypothesized that the CCR5-delta 32 allele may modulate the severity of disease in RA. A total of 160 RA-patients (71 and 89 with severe and non-severe phenotypes, respectively) and 500 healthy individuals from the same Caucasian population (Asturias, northern Spain) were genotyped. Carriers of the CCR5-delta 32 allele were at a significantly higher frequency (P = 0.012) in non-severe compared to severe patients (17% vs 4%). Our results suggest that the CCR5-delta 32 polymorphism is a genetic marker related to the severity of RA. PMID- 11196707 TI - Lack of association between the interferon regulatory factor-1 (IRF1) locus at 5q31.1 and multiple sclerosis in Germany, northern Italy, Sardinia and Sweden. AB - Interferon regulatory factor-1 (IRF-1) is a transcriptional inducer of the interferon-beta (IFN-beta) gene and other interferon-stimulated genes. A GT repeat polymorphism in the 7th intron of the IRF-1 gene was used as a marker to test for association with multiple sclerosis (MS) in a case-control study including individuals from Germany, Northern Italy and Sweden. In none of these populations, did we find any significant allelic association with disease. This lack of association was confirmed by testing transmission disequilibrium of individual IRF1 alleles in a representative sample of Sardinian simplex MS families. No deviation of the expected 50% transmission rates was seen. Therefore, our work does not provide evidence in favor of IRF1 being a candidate for conferring genetic susceptibility to, or protection against, MS in Europe. PMID- 11196708 TI - A new polymorphism in the promoter region of the human interleukin-16 (IL-16) gene. AB - Interleukin 16 (IL-16) is a chemotactic cytokine which binds to CD4 and affects T cell activation. Here we report a novel single nucleotide polymorphism, T to C, in the promoter region of the IL-16 gene in two distinct Asian populations, Japanese and Thai. This mutation occurs at an allele frequency of approximately 22% and 18%, respectively. Although IL-16 potently suppresses replication of human immunodeficiency virus type 1 (HIV-1), we observed no significant difference in the allele frequency of this polymorphism between HIV-1-infected and non-HIV-1-infected individuals in both Asian populations. Since differential IL-16 levels have been reported to be associated with inflammatory diseases such as systemic lupus erythematosus, atopic dermatitis and allergic asthma, it would be of interest to analyze the allele frequency of this mutation in patients with these autoimmune and allergic diseases. PMID- 11196709 TI - CTLA-4 in autoimmune diseases--a general susceptibility gene to autoimmunity? AB - For most autoimmune disorders, the pattern of inheritance is very complex. The major histocompatibility complex (MHC) gene complex has been implicated as the major genetic component in the predisposition to these diseases but other genes are likely to be involved. Based on function and experimental data, the gene encoding cytotoxic T lymphocyte-associated antigen 4 (CTLA4) has been suggested as a candidate gene for conferring susceptibility to autoimmunity. In this review, we critically evaluate the evidence for pathogenetical involvement of CTLA-4 in the different autoimmune diseases with focus on the possible role of genetic variation of the CTLA4 locus. PMID- 11196710 TI - Cytokine (TNF alpha, LT alpha and IL-10) polymorphisms in inflammatory bowel diseases and normal controls: differential effects on production and allele frequencies. AB - The influence of biallelic polymorphisms in the tumour necrosis factor-alpha (TNF alpha), lymphotoxin-alpha (LT alpha) and interleukin-10 (IL-10) genes on stimulated TNF alpha and IL-10 production was studied in ulcerative colitis (UC) patients, Crohn's disease (CD) patients and in healthy controls. A polymerase chain reaction sequence-specific primer (PCR-SSP) system was developed to type nine biallelic polymorphisms, three in each of the TNF alpha, LT alpha and IL-10 genes. Production of the TNF alpha and IL-10 was measured by ELISA in lipopolysaccharide (LPS) stimulated whole blood. Four haplotypes of the TNF alpha gene, three haplotypes of LT alpha and three haplotypes of IL-10 were identified. No significant differences in haplotype frequencies were found between patients and controls overall. On subgroup analysis however, haplotype TNF-2 was more frequent in women with extensive colitis compared to distal colitis (31% vs 12%; P = 0.028). This difference was even greater for the combined TNF-2-LT alpha-2 haplotype (56% vs 21%; P = 0.0007). The TNF-2 and LT alpha-2 haplotypes were associated with higher TNF alpha production in CD patients, and the TNF-4 haplotype was associated with lower TNF alpha production in UC patients. The A allele in the IL-10 promoter region at position -1082 was associated with decreased IL-10 production in CD patients and controls (P = 0.005, P = 0.015 respectively). These data provide evidence that the effect of TNF alpha, LT alpha and IL-10 gene polymorphisms on cytokine production differ in CD, UC patients and controls. PMID- 11196711 TI - SPLASH (PLA2IID), a novel member of phospholipase A2 family, is associated with lymphotoxin deficiency. AB - Lymphotoxin (LT) deficient mice have profound defects in the splenic microarchitecture associated with defective expression on certain gene products, including chemokines. By using subtraction cloning of splenic cDNA from wild-type and LT alpha or TNF/LT alpha double deficient mice we isolated a novel murine gene encoding a secretory type phospholipase A2, called SPLASH. The two major alternative transcripts of SPLASH gene are predominantly expressed in lymphoid tissues, such as spleen and lymph nodes. SPLASH maps to the distal part of chromosome 4, to which several cancer-related loci have been also mapped. PMID- 11196712 TI - Susceptibility to Leishmania major infection in mice: multiple loci and heterogeneity of immunopathological phenotypes. AB - Susceptibility as opposed to resistance of mouse strains (e.g., BALB/c vs C57BL/6) to Leishmania major has been attributed to a defective Th1 and a predominant Th2-response, resulting in increased IL-4 and IgE production, and decreased interferon gamma (IFN gamma) production, macrophage activation and elimination of parasites. Here we report dissection of genetic and functional aspects of susceptibility to leishmaniasis using two contrasting inbred strains BALB/cHeA (susceptible) and STS/A (resistant) and a resistant Recombinant Congenic (RC) Strain, CcS-5/Dem, which carries a random set of 12.5% of genes from the strain STS and 87.5% genes from the susceptible strain BALB/c. Linkage analysis of F2 hybrids between the resistant RC strain CcS-5 and the susceptible strain BALB/c revealed five loci affecting the response to the infection, each apparently associated with a different combination of pathological symptoms and immunological reactions. The correlation between Th2-type immune reactions and the disease in the F2 mice was either absent, or it was limited to mice with specific genotypes at loci on chromosomes 10 and 17. This suggests that the resistance vs susceptibility is influenced by mechanisms additional to the postulated antagonistic effects of Th1 and Th2 responses, and that the host's genotype affects the development of leishmaniasis in a complex way. PMID- 11196713 TI - Is interleukin-6 important in inflammatory bowel disease? AB - The IL-6 gene maps to an area of chromosome 7 known to be significant for susceptibility to inflammatory bowel disease. The functional effects of interleukin-6 (IL-6) polymorphisms in the 4th intron and in the 3' flanking region of IL-6 gene were studied in 192 inflammatory bowel disease patients and healthy subjects. A polymerase chain reaction with sequence-specific primers (PCR SSP) was used to determine a G to A polymorphism (* at position 4470 in intron 4 of IL-6 gene). Four alleles in the 3' flanking region were studied using a variable number of tandem repeats PCR (VNTR-PCR) amplification. Production of IL 6 was measured in lipopolysaccharide (LPS) stimulated whole blood samples by an enzyme-linked immunosorbent assay (ELISA). A modest increase in the frequency of the IL-6*G allele was noted in Crohn's disease (CD) patients (50%) and ulcerative colitis (UC) patients (46.1%) as compared to controls (39.8%, P = 0.025). We were unable to find any significant functional effect of the IL-6 polymorphisms tested on IL-6 protein production. We postulate that the IL-6 polymorphisms investigated here may be in linkage disequilibrium with a susceptibility gene and that they may be utilised as genetic markers. PMID- 11196714 TI - Eosinophilia is attenuated in experimental colitis induced in IL-5 deficient mice. AB - Tissue eosinophilia is a feature of idiopathic inflammatory bowel disease and other forms of colonic inflammation but it is not clear whether the role of eosinophils in the disease process is to contribute to tissue damage. Interleukin 5 (IL-5) stimulates production and activation of eosinophils in vitro and enhances immunoglobulin A (IgA) production. As very little is known about the function of IL-5 in the colon, the aim of this study was to assess its role in colonic inflammation. IL-5 deficient mice were studied using the dextran sulphate sodium (DSS)-induced colitis model and the results compared to a congenic IL-5+/+ strain. The absence of IL-5 resulted in reduction of tissue eosinophilia (P < 0.0001) but was not reflected in differences in the severity of the disease (P > 0.5) or in the extent of tissue damage in this model of colitis. Numbers of immunoglobulin-containing cells in IL-5 deficient mice were similar to those in the IL-5+ mice. We conclude that the main role of IL-5 in DSS-induced colonic inflammation is to attract a population of eosinophils which do not appear to contribute significantly to the initiation or development of tissue damage in this model of colitis. PMID- 11196715 TI - Genetic polymorphism of IL-12 p40 gene in immune-mediated disease. AB - Understanding of the genetic basis of autoimmune diseases is currently incomplete. Cytokine gene polymorphisms warrant consideration as factors explaining variation in the human immune and inflammatory responses and as candidate susceptibility genes for related pathological states. Interleukin 12 (IL-12) is a key regulator of the polarisation of immune responses to T helper 1 or 2 categories and plays a role in autoimmune and infectious diseases. Using a bioinformatic strategy, we aligned cDNA and expressed sequence tag sequences to identify putative polymorphic regions of the IL-12 p40 gene. Position 1188 in the 3' untranslated region (UTR) was polymorphic with the frequency of the common allele around 80% in healthy UK Caucasoids. PCR genotyping of multiple Caucasoid groups and an African group showed significant population variation. In a case control design, the polymorphism was not associated with rheumatoid arthritis, Felty's syndrome or large granular lymphocyte syndrome with arthritis or multiple sclerosis. A nonsignificant increase in the B allele frequency was observed in the rare large granular lymphocyte syndrome without arthritis (odds ratio 2.02 95% CI 0.95-4.3). This new genetic marker could be useful in anthropological studies and should be investigated in other autoimmune, allergic, inflammatory and infectious diseases. PMID- 11196716 TI - A TNFR2 3' flanking region polymorphism in systemic lupus erythematosus. AB - The role of pro-inflammatory cytokines in systemic lupus erythematosus (SLE) remains somewhat controversial. Several studies have shown increased production of TNF alpha and IL-6 in patients with SLE. Increased production of IL-6, TNF alpha, and IL-1 soluble receptors have also been reported. This finding is provocative because the soluble receptors have the capacity to act as antagonists. Several other inflammatory disorders are also associated with increased production of soluble TNF alpha receptors suggesting that this may be a general compensatory mechanism designed to down-regulate inflammation. The recent identification of an SLE disease susceptibility locus near the TNFR2 locus (TNFR p75) suggested the hypothesis that genetically driven differences in soluble TNFR2 production could play a role in the genetic susceptibility to SLE. We therefore characterized the frequency of a genetic polymorphism in the 3' untranslated region of the TNFR2 gene in Caucasoid SLE patients and geographically matched controls. No difference in the gene frequency of the two base-pair polymorphism in SLE patients compared to controls was found, nor was there any association with any particular clinical phenotype. PMID- 11196717 TI - A polymorphic microsatellite marker in the human p55 TNF receptor, CD120a. AB - We provide characterization of a highly polymorphic dinucleotide repeat in the human TNF-receptor 1 gene (TNFR1, TNFRp55, CD120a). We have observed 11 alleles at this locus in individuals from the West of Scotland. In a panel of healthy, unrelated individuals from the West of Scotland (n = 143), the overall heterozygosity was 68%, indicating the potential usefulness of these markers in immunogenetic studies. PMID- 11196718 TI - New polymorphisms in the IL-10 promoter region. AB - Interleukin-10 (IL-10) is an important immunoregulatory cytokine. We searched for new sequence variations in the 5' flanking region of the IL-10 gene by denaturing high performance liquid chromatography. A 3996 bp region spanning position -3934 to +61 was amplified in 12 polymerase chain reaction (PCR) fragments and each fragment was screened for variations in 23 Italian individuals. The following eight sequence variations all consisting of single base pair substitutions were identified: -3533A/T, -2769A/G, -2739A/G, -2013A/G, -1349A/G, -1255C/T, -851A/G, 657A/G. The new polymorphisms were analysed in an additional panel of random Italian individuals. The same samples were also tested for the IL10.G and IL10.R microsatellites, and for the two previously described single nucleotide polymorphisms (SNPs) at positions -1082 and -592. Highly significant pairwise linkage disequilibria were observed between alleles at most SNPs. Three major haplotypic combinations of alleles at multiple SNP sites were observed. PMID- 11196719 TI - A Bsr BI polymorphism in exon 1C of the human interleukin-1 receptor type I (IL 1RI) gene. AB - We have identified a single nucleotide polymorphism in the 5' region of the human interleukin-1 receptor type I (IL-1RI) gene, a C-->A transversion at position 52 in exon 1C (GenBank accession number AF172151) which creates a Bsr BI restriction endonuclease site. Allele frequencies in a Caucasian population were 0.72 (C allele) and 0.28 (A allele). PMID- 11196720 TI - Biliary complications associated with laparoscopic cholecystectomy--an analysis of common misconceptions. AB - BACKGROUND: Several views are expressed by surgeons on biliary complications following laparoscopic cholecystectomy as follow: most are caused by trainees; complications occur in the presence of difficult anatomy/pathology; injuries occur more proximally than at open cholecystectomy; most injuries are recognised immediately and most can be managed non-operatively. The aim of our study was to determine if these views are substantiated in clinical practice. METHODS: The mode of presentation, management and outcome of thirty-two patients referred to a hepatobiliary unit over a seven year period were analysed. RESULTS: In 72% of cases the initial operator was a consultant. Five of the 32 complications (16%) occurred in the presence of difficult anatomy/pathology. Two patients had proximal biliary tree injuries, the only mortalities (two) occurring in this group. Only 41% of injuries were detected immediately; 87% required surgical intervention, hepaticojejunostomy being the most common procedure performed (75%). CONCLUSION: Our study shows that the majority of bile duct injuries are not caused by trainees, do not occur because of unusual anatomy/pathology, do not occur in the proximal biliary tree and are not recognised at the time of operation. Most injuries ultimately require major reconstructive surgery for definitive management. PMID- 11196721 TI - Proximal femoral fracture in Northern Ireland between 1985-1997--trends and future projections. AB - The aims of this study were to identify changing trends with time of the incidence of proximal femoral fracture and to enable future number of hip fractures to be projected. Hospital theatre records in Northern Ireland were surveyed in 1985, 1991, 1994 and 1997 to establish the number of surgical procedures for proximal femoral fracture. The age and sex specific rates for males and females aged 50+ years were calculated. Analysis of age and sex specific incidence rates was undertaken using linear regression and Poisson regression. A 1.6% increase per annum (95% CI 1.0-2.2) was noted in males and females from 1985 to 1997. Projected increases in rates of proximal femoral fracture were calculated using population projection for 2001, 2006, 2011 and 2016. Modelling (a) assuming the age standardised rates in 1997 remain static and continue predicted a 55% fracture increase in males and a 29% increase in females by 2016, (b) assuming the secular increases continued predicted a 93% fracture increase in males and a 67% increase in females and (c) assuming further linear growth on a log-scale predicted a fracture increase in males of 135% and 99% in females. The number of proximal femoral fractures in Northern Ireland is increasing faster than that anticipated due to demographic changes alone, supporting a secular increase which was evident throughout the period of time studied, in contrast to that reported from other regions in the United Kingdom. PMID- 11196722 TI - Periprosthetic femoral fractures in Northern Ireland. AB - Twenty-five patients with periprosthetic femoral fractures were admitted to the Ulster Hospital between August 1998 and May 2000. Average age was 77 years (range, 42-96 years) with a female to male ratio of 2:1. Twenty-four of the fractures occurred following primary joint arthroplasty on average 7.6 years from insertion of the primary prosthesis. One patient sustained an intraoperative fracture during revision surgery. In the majority (80%), the periprosthetic femoral fracture was associated with a traumatic event. On average, two days elapsed from the time of injury until admission to our unit. Time from admission to surgery was on average 4 days. All patients were treated by open fracture fixation. Duration of stay in the fracture unit was on average 20 days. Prior to their fracture 92% of patients were living at home and 84% were mobile either unaided or with the use of a stick. At most recent review, 72% are back living at home and 60% are mobile either unaided or with the use of a stick. We emphasise that there is the likelihood of an increase in periprosthetic femoral fractures due to the increasing number of primary arthroplasties being performed on a more active, ageing population. Preventative measures and cost implications are also discussed. PMID- 11196723 TI - Drugs for dementia: the first year. An audit of prescribing practice. AB - In March 1998 the Department of Health and Social Services issued prescribing guidelines for the use of drugs for dementia. A criterion based audit of 202 consecutive cases was undertaken over one year which showed that the prescribing guidelines in general were being followed. A small number of patients, 3, were prescribed the drugs outside the guidelines and most failures, 10, were due to poor recording of data in the clinical record. Despite the recommendation of the DHSS no agreed shared care protocols have been implemented but this does not seem to have affected access to these drugs. As a result of this audit changes have been made with regard to documentation of patient assessments and suggestions made to review Clinical Resource Efficiency Support Team (CREST) guidelines. PMID- 11196724 TI - Non-small cell lung cancer and CHART (continuous hyperfractionated accelerated radiotherapy)--where do we stand? AB - This paper reviews the use of hyperfractionated and/or accelerated radiation therapy in the curative treatment of non-small cell lung cancer, and explains the scientific rationale behind the development of these regimes. The indications, practicalities and economics of introducing them routinely are addressed. Novel radiotherapy techniques are further discussed in the context of current developments and on-going clinical trials. PMID- 11196725 TI - Renal replacement therapy in Ireland--the Belfast experience. Based on the 2nd J Creery Ferguson Memorial Lecture of the Royal College of Physicians of Ireland on the occasion of the bicentenary of the Royal Victoria Hospital--7th March 1997. PMID- 11196726 TI - Airway management in a patient with a nail-gun injury to the floor of the mouth. PMID- 11196727 TI - Curative surgery following failure of vancomycin therapy: a case report of methicillin resistant staphylococcal endocarditis on a native mitral valve. PMID- 11196728 TI - Conservative management of major liver trauma. PMID- 11196729 TI - Cystic tumours of the pancreas--the importance of correct diagnosis and treatment. PMID- 11196730 TI - Volvulus of the gallbladder. PMID- 11196731 TI - The delivery of the first babies conceived using testicular sperm in Northern Ireland. PMID- 11196732 TI - Twin pregnancy with a living fetus and coexisting complete hydatidiform mole. PMID- 11196733 TI - Acute bilateral anterior dislocations of the shoulders. PMID- 11196734 TI - An unusual case of patellar dislocation. A case report and literature review. PMID- 11196735 TI - Aspirin-related small bowel diaphragm disease identified during emergency laparotomy. PMID- 11196736 TI - The declining autopsy rate and clinicians' attitudes. AB - The autopsy rate has been declining worldwide for decades. This study determined the overall and differential autopsy rates for the Royal Victoria Hospital, Belfast for the years 1997-1999 inclusive. Trends were examined by comparison with previously collected data for the years 1990, 1991 and 1993. Reasons for the decline in autopsy rates as perceived by hospital clinicians were assessed by means of a questionnaire. Over the last decade, there has been a steady decline in the overall autopsy rate from 30.4% in 1990 to 18.4% in 1999. This is due to a decrease in the hospital autopsy rate from 21.6% in 1990 to 7.9% in 1999. The coroner's autopsy rate has remained comparatively unchanged at around 11%. The decline in the overall and hospital autopsy rates involves all of the principal bedholding directorates, but is most dramatic in medicine, surgery and intensive care, where hospital autopsy rates are currently 7% or less. The main reasons for this decline as perceived by clinicians are difficulty in obtaining consent from relatives and advances in modern diagnostic techniques. The findings of this enquiry are in keeping with trends elsewhere, despite repeated studies which clearly demonstrate the continuing value of the autopsy in clinical practice. Recent publicity concerning the retention of organs can only have an adverse affect. Pathologists and clinicians who value the autopsy must become actively engaged in both public and medical education. Renewed emphasis must be placed on the importance of the autopsy in teaching, training and clinically relevant research, and as a means of medical audit. PMID- 11196737 TI - Paediatric renal transplantation in Northern Ireland (1984-1998). AB - Over the last 20 years a comprehensive paediatric nephrology service has been developed in Northern Ireland, based in the academic medical unit at the Royal Belfast Hospital for Sick Children (RBHSC). In the 15 years 1984-1998 a total of 77 renal transplants have taken place in patients aged 18 years and under. Initially transplants were only considered in children over five years of age but in the past eight years children as young as two years have successfully received kidneys. Aggressive nutritional support combined with peritoneal dialysis has enabled survival to a size when transplantation is feasible. The 5 year graft survival was 64%, with two children dying following transplantation. The complexity of managing this age group is reflected by the fact that a total of 10 transplants (13%) failed in the first 30 days. These figures compare favourably with statistics reported by similar paediatric centres from across the United Kingdom and Republic of Ireland, and with local results in adult patients. This demonstrates that a successful end stage renal replacement programme for children is achievable in a relatively small population, which is geographically isolated. PMID- 11196738 TI - Multiple sclerosis in Northern Ireland: a historical and global perspective. AB - The uneven worldwide distribution of multiple sclerosis has been of interest to epidemiologists, neurologists and statisticians for over a century, prevalence rates for the disease apparently being determined by variations in age, gender, geography, race and ethnic group. Northern Ireland has been recognised as an area of high MS prevalence since the truly seminal work of Allison and Millar almost 50 years ago. The most recent study in Northern Ireland was undertaken in 1996 and involved the neighbouring districts of Coleraine, Ballymena, Ballymoney and Moyle (population, 151,000). Overall, 254 definite and probable cases were identified (prevalence: 168.2/100,000) with a further 34 suspected cases (overall prevalence: 190.7/100,000). Females predominated (ratio, 2.1:1) and the average age at onset was 31.6 years. The highest age specific prevalence rate for females was in the 35-44 years old age group (519.6/100,000) and for males was in those aged 55-64 (292.3/100,000). The spectrum of disability was broad and 20% could be considered to have relatively "benign" disease. These figures sadly confirm that Northern Ireland has one of the highest and rising MS prevalence rates in the world and implies an enormous potential for societary costs. PMID- 11196739 TI - Discovery of the Rett syndrome gene and its function. PMID- 11196740 TI - Neonatal tetanus in the southeast of Turkey: risk factors, and clinical and prognostic aspects. Review of 73 cases, 1990-1999. AB - Although neonatal tetanus (NT) can be prevented by immunization of expectant mothers and by good hygiene and asepsis during delivery, it is still a common cause of neonatal mortality in developing countries. The objective of this study was to determine indicators in NT. We reviewed the clinical records of 73 neonates admitted to the Pediatric Infectious Diseases Ward of Dicle University Hospital, Diyarbakir, Turkey, with the diagnosis of NT. Delivery had occurred at home by untrained traditional birth attendants in all cases. None of the mothers had immunization with tetanus toxoid during pregnancy. The median age of infants at presentation was 7.3 days and the mean age at onset of symptoms was 5.6 +/- 2.8 days. The overall mortality was found to be 52 percent. Mortality was significantly associated with an incubation period of 4.3 days or less and fever. The incidence of NT in Turkey is on the decline due to widespread tetanus toxoid use in pregnant women, but in some regions, especially in the so-called rural poor areas, there is still risk of preventable diseases. Hygienic deliveries and immunization of pregnant women are very important for the prevention of NT deaths, and universal prenatal care, including education programs on appropriate perinatal and cord care, can significantly reduce NT incidence and mortality in developing countries. PMID- 11196741 TI - Reactogenicity and immunogenicity of a new measles-mumps-rubella vaccine containing RIT 4385 mumps virus strain in healthy Turkish children. AB - A total of 44 children aged between 15-18 months were randomly vaccinated either with a new measles-mumps-rubella (MMR) vaccine (Priorix, SmithKline Beecham) or a commercially available MMR vaccine (MMR-II, Merck) to compare the reactogenicity and immunogenicity. No local symptoms or fever was reported. Seroconversion rates of the study vaccine were 100, 95 and 100 percent for measles, mumps and rubella, respectively. The seroconversion rates for the control vaccine were 100, 94.7 and 95.5 percent, respectively. The geometric mean titers (GMT's) for the study and control groups were 1695, 95, 58; and 2198, 1183 and 47; respectively. In conclusion, the new MMR vaccine containing RIT 4385 mumps strain derived from the Jeryl Lynn strain was shown to be immunogenic and safe in healthy Turkish children. Further post-marketing surveillance should be conducted. PMID- 11196742 TI - Carnitinuria in rickets due to vitamin D deficiency. AB - In this study, we measured the serum-urine total carnitine levels and PTH levels before and after treatment in 18 patients with nutritional rickets. The urine and blood samples were taken on the first (pretreatment) and the 15th day of the study (post-treatment). The total carnitine levels of serum and urine samples, serum PTH and serum-urine creatinine concentrations were determined. We found that the levels of carnitine excreted in the urine on the first (pre-treatment) and on the 15th day (post-treatment) were higher than the reference levels. Decrease in carnitine excretion on the 15th day seemed to be correlated with decrease in aminoaciduria at that time. The study showed a significant correlation between urinary carnitine excretion and serum PTH levels. In our study we did not find any significant difference between the serum total carnitine levels on the first (pre-treatment) and the 15th day (post-treatment), and both values were lower than the reference values for the same age group. We observed that the total serum carnitine levels did not change on the 15th day of the post-treatment period in spite of a decrease in urinary carnitine excretion. The results of the present study indicated that carnitine metabolism is disturbed in nutritional rickets. Further evaluation of rickets cases and new studies will probably lead to a better understanding of carnitine metabolism in nutritional rickets. PMID- 11196743 TI - The relationship between osteocalcin levels and sexual stages of puberty in male children. AB - Osteocalcin is a specific and reliable marker which increases with rapid bone turnover and gives data about bone metabolism. The pubertal growth spurt is also known as a good example of rapid bone turnover. The aim of this study was to determine whether osteocalcin is a useful marker for the pubertal growth spurt period. In this study, osteocalcin levels in male adolescents were examined in relation to their sexual maturation stage and age. The osteocalcin levels and alkaline phosphatase levels were compared during the pubertal growth spurt. Serum osteocalcin and alkaline phosphatase levels were evaluated in 100 eligible healthy male children and adolescents (aged 10 to 17 years). Five groups (n: 20 each) of children and adolescents were formed according to their sexual maturation stages. Finally, the subjects were divided into three main groups in relation to the pubertal growth spurt and sexual maturation stages. Data were evaluated and compared among these three groups: First group = Stage 1 (prepuberty) + Stage 2 (early puberty) consisted of 40 (20 + 20) children and adolescents. Their mean osteocalcin value was 17.2 +/- 6.3 ng/ml and alkaline phosphatase 573.8 +/- 143.9 IU/L. Second group: Stage 3 + Stage 4 consisted of 40 (20 + 20) children and adolescents. These groups were known as the pubertal growth spurt groups. Their mean osteocalcin value was 29.4 +/- 10.6 ng/ml and alkaline phosphatase 728.4 +/- 233.9 IU/L. Third group: In this group, there were 20 children and adolescents who reached Stage 5 of sexual maturation and whose pubertal growth spurt was slowing. Their mean osteocalcin value was 15.3 +/- 5.8 ng/ml and alkaline phosphatase 435.8 +/- 184.8 IU/L. During the pubertal growth spurt, there is a relationship between bone remodelling and increasing osteocalcin and alkaline phosphatase levels. When sexual maturation reaches Stage 4 at 14 years old, osteocalcin and alkaline phosphatase levels make a peak, associated with the rapid growth in height. As sexual maturation reaches Stage 5, osteocalcin and alkaline phosphatase levels gradually decrease with growth maturation and their levels decline to the level of adults at the completion of this period. Our study showed that osteocalcin and alkaline phosphatase levels can be used as markers for evaluation of the growth spurt period. PMID- 11196744 TI - Analysis of 2017 Holter records in pediatric patients. AB - Holter monitoring (HM) is widely used in arrhythmic disorders of adult patients; however, studies in the pediatric age group are limited. This study aims to determine the value of HM in diagnosis and treatment of disorders related to arrhythmias in pediatric patients. We examined 2,017 Holter records of 1,500 children who applied to our institution between November 1994 and October 1998. The age ranged from 0-24 years (52% male, 48% female). The indications for HM were screening for arrhythmic symptoms (palpitation, chest pain, syncope) in 67 percent, monitoring dysrhythmic therapy in 17 percent, postoperative control in five percent, and pacemaker control in four percent. Palpitation is the leading presenting symptom, with more frequent findings of supraventricular extrasystole (SVE), supraventricular tachycardia (SVT), ventricular extrasystole (VE) and complete heart block (CHB) when compared to other symptoms. Only 5.3 percent of the patients had arrhythmic symptoms during monitoring and asymptomatic patients had more frequent arrhythmias. SVT, VE, and CHB are more frequent findings in the abnormal heart with previous cardiac operations. The diagnostic yield is low with arrhythmic symptoms in the pediatric age group; however, HM enables cumulative evaluation of heart rhythm and rhythm variability, which is important in diagnosing silent arrhythmias in high risk groups (abnormal heart, postoperative heart). PMID- 11196745 TI - Complications of pediatric cardiac catheterization: 18-month study. AB - Pediatric cardiac catheterization may be indicated under certain conditions, but is associated with some risk. The purpose of the study was to evaluate the complications associated with diagnostic and interventional catheterization procedures done over an 18-month period in our laboratory. Of the 230 cardiac catheterizations, 204 were solely diagnostic in nature. Eleven percent were interventional catheterizations including aortic and pulmonary valvuloplasties and balloon atrial septostomy. Six percent of the patients constituted grown-up congenital heart disease (GUCH). The median age was 34 months excluding the GUCH group. There was one death below one year of age (0.4% mortality) occurring six hours after the diagnostic catheterization; it was attributed to the underlying disease. There were eight complications (3.4%) that we would consider serious, including atrial flutter, ventricular tachycardia, severe hypercyanotic spell, seizure, transient complete heart block, peripheral vascular injury which resulted in pseudoaneurysm formation of the femoral artery requiring surgical intervention, and transient pulse loss. When catheterization is necessary, it should be carried out as efficiently as possible with awareness of conditions that probably increase the risk of a clinically important event. Although patients undergoing cardiac catheterization are now younger and have more complex cardiac abnormalities, the procedure seems to have become safer when compared to previous literature. PMID- 11196746 TI - Thymic enlargement in childhood. AB - Thymic masses constitute one of the least common mediastinal masses in childhood. While producing symptoms of airway compromise, they also raise the suspicion of malignancy when detected. Radiological, operative and pathological findings of patients that have been operated for thymic masses in our institution is presented in this paper. Nine patients were operated in our institution during a 12-year-period between 1985-1997 for thymic masses. Ages of the patients ranged from four months to 13 years. With the exception of one, who was diagnosed with a routine chest x-ray, all the patients had respiratory complaints. All the patients had been evaluated with computed tomography preoperatively. In total, seven sternotomies and four thoracotomies were performed to reach the anterior mediastinum. The distribution of masses was as follows two malignant thymomas, three thymic hyperplasia, one lymphocyte-rich thymoma, one epithelial thymoma, one cystic thymoma and one lymphoblastic lymphoma. Although rare, thymic enlargement may be a cause of intractable respiratory complaints in childhood. Because of the high incidence of primary malignancy of the mediastinal neoplasms in childhood, thymic enlargement requires accurate pathological diagnosis and treatment. Median sternotomy with intensive anesthetical care allows proper tumoral exposure. PMID- 11196747 TI - The clinical outcome of childhood masturbation. AB - This study was performed to investigate the clinical outcome of childhood masturbation. For this purpose 50 children (mean age = 48.7 +/- 24.5 months, 34 girls females and 16 boys males) with masturbation symptoms were examined at first visit to the Department of Child Psychiatry and two years thereafter with psychiatric interviews. The mean masturbation frequency at the initial interview was significantly decreased after two years. It was noted that 39 children (78%) were completely recovered and 11 children (22%) continued to masturbate after two years. Children who did not recover were significantly younger, began to masturbate earlier and masturbated more frequently than others at the time of initial evaluation. It was concluded that the findings about the beneficial effect of sedative drugs in combination with parental guidance, education and means for behavior modification were promising. PMID- 11196748 TI - Neonatal morbidity and mortality associated with maternal HELLP syndrome. AB - The syndrome of hemolysis, elevated liver enzymes and low platelet count (HELLP syndrome) is a severe form of preeclampsia and eclampsia. To compare the impact of HELLP syndrome and hypertension in pregnancy (HIP) on neonatal morbidity and mortality, 11 infants born to mothers with HELLP syndrome were recruited between 1993 and 1997 from neonatal records. They were compared to 11 infants born to mothers with HIP and 11 control infants born to healthy mothers matched for gestational age, postnatal age and gender. Cesarean section rate was higher in the HELLP group than in the controls (p < 0.05). HELLP group infants had lower Apgar scores (54.5% < 1 at 5th min), than controls (9.1%) (p < 0.05). Both HELLP and HIP group infants showed a higher incidence of intrauterine growth retardation (63.6% and 54.5%, respectively) than the controls (9.1%) (p < 0.05). The incidence of respiratory distress syndrome (RDS) was similar in HELLP and HIP groups and was greater than that in controls (p = NS). Additionally, the neonatal death rate was the highest in the HELLP group (p = NS). PMID- 11196749 TI - Clinicopathological conference: an 11-year-old boy with recurrent infections, hypertension, skin rash, and nephritic syndrome. AB - In this clinicopathological conference, an 11-year old boy who presented with recurrent pyogenic infections, hypertension, malar rash, various skin lesions and nephritic syndrome since five years of age is discussed. He was hospitalized for clinical investigation with skin and renal biopsies at 10 years of age. Using clinicopathological data obtained from his last admission, a clinical diagnosis was reached, and the disorders of the complement system causing patients to show these signs or symptoms are emphasized. At the end of the discussion, a clinicopathological correlation is given for making the diagnosis. PMID- 11196750 TI - Triosephosphate isomerase deficiency with elevated sweat chloride test: report of a case. AB - A 15-month-old girl with severe hemolytic anemia and progressive respiratory failure is presented. She was well until the age of six months when she developed a pulmonary infection. During the next six months, she had frequent respiratory infections and her paleness became evident. At the age of 12 months, she was observed to have easy fatigability and muscle weakness, and she received her first blood transfusion. She was referred to our hospital at the age of 15 months. The physical examination revealed a malnourished girl with hypotonia, nystagmus, generalized muscle weakness and severe breathing difficulty requiring ventilatory support The hemoglobin (Hb) was 9.7 g/dl; hematocrit (Hct) 29%, mean corpuscular volume (MCV) 101 fl and reticulocyte count 15%. Peripheral blood smear revealed macrocytosis and stomatocytosis (30% of the red cells) and polychromasia. Sweat chloride test was 90 and 94 mEq/L on two separate occasions. The serum vitamin E level was 0.26 mg/dl (N: 0.44-0.68). She was found to be heterozygous for factor V Leiden mutation. Although malnutrition, low serum vitamin E and elevated sweat chloride test were suggestive of cystic fibrosis, this diagnosis failed to account for all the findings in the patient. A search for a red cell enzyme deficiency revealed that the red cell triosephosphate isomerase (TPI) activity was low. DNA analysis showed the 315 G-C (105 Glu-Asp) TPI mutation, thus confirming the diagnosis of TPI deficiency. PMID- 11196751 TI - Familial mullerian agenesis. AB - Mullerian agenesis is characterized by the absence of the fallopian tubes, uterus and internal portion of the vagina. Patients have normal female phenotype and genotype, with normal secondary sex characteristics but with amenorrhea. We report a family in which mullerian agenesis was diagnosed in three siblings and their two paternal aunts. This family was ascertained when the proband was evaluated for primary amenorrhea. She had normal secondary sexual development. Her karyotype was 46, XX. Ultrasound examination and magnetic resonance imaging of the pelvis revealed absence of the uterus and vagina. The proband had three sisters and two of them showed similar physical and radiological findings. Two of the proband's paternal aunts had no uterus. Although the pathogenesis of mullerian agenesis is well understood, the etiology and genetics are still unknown. Various forms of inheritance patterns have been suggested by several authors. In conclusion, it would appear that mullerian agenesis is influenced by multifactorial inheritance and polygenic and familial factors. PMID- 11196752 TI - Dilatation of a restrictive interatrial communication using a balloon angioplasty catheter. AB - Balloon atrioseptostomy is a life-saving procedure palliating certain congenital heart defects like transposition of the great arteries, right or left atrioventricular valve atresia, hypoplastic left heart syndrome, and pulmonary hypertension. Occasionally the Rashkind balloon septostomy technique may be ineffective in creating an adequate interatrial communication. We performed balloon dilatation of a restricted atrial septal defect using a balloon angioplasty catheter in a three-month-old infant. PMID- 11196753 TI - Pseudomonas sepsis with neutrophagocytosis in a premature newborn. AB - Secondary hemophagocytic syndrome may develop during certain severe infections commonly due to viral infections, but is rarely associated with bacterial infections, and its appearance in a premature newborn is uncommon. We present a case of hemophagocytosis during Pseudomonas aeruginosa septicemia in a premature infant. After sepsis treatment with imipenem-cilastatin and aminoglycoside, remission of hemophagocytosis was achieved. PMID- 11196754 TI - Double meningocele. Case report. AB - The coexistence of two distinct meningoceles of the spine is a very unusual event. We report a three-day-old boy with double meningoceles at the thoracic and lumbar levels. The connection between the stalk of the thoracic meningocele and the spinal cord, as seen on magnetic resonance imaging, showed a neurological involvement in this lesion. Our case is only the third without association of congenital anomalies or neurofibromatosis to be reported to date. PMID- 11196755 TI - Congenital generalized infantile myofibromatosis and neonatal hemochromatosis. An autopsy case report. AB - An autopsy case of congenital infantile myofibromatosis and neonatal hemochromatosis is reported. A thirty-six-hour-old baby girl had multiple subcutaneous nodules in addition to multiple visceral involvement of heart, lungs, pharynx, larynx, stomach, small bowel, large bowel, pancreas, kidneys, spleen, thyroid, adrenal glands, lymph nodes, peripheral nerves, meninges and soft tissues. In these tumoral nodules, three types of histological patterns were observed: 1-hemangiopericytoma-like, 2-mixed, and 3-pure spindle cell. Tumor cells were immunohistochemically positive for actin, and negative for desmin, muscle-specific antigen, and estrogen, related protein. The histological and immunohistochemical findings of the case suggested that a close relationship may exist between infantile myofibromatosis and infantile hemangiopericytoma. In addition to infantile myofibromatosis, neonatal hemochromatosis characterized by iron deposition in parenchymatous organs such as liver, pancreas, lungs, thyroid, and adrenal glands was another important characteristic of the case. PMID- 11196756 TI - Congenital sick sinus syndrome with breath holding and severe syncope episodes during infancy. A case report. AB - Sick sinus syndrome is a rare cause of bradycardia in children without structural heart disease. A case of profound sinus bradycardia, sinus arrest with junctional escape, and pauses in a two-year-old infant with breath-holding and syncope episodes is presented. As a result of these clinical symptoms and electrocardiographic findings, the patient with sick sinus syndrome underwent implantation of transvenous ventricular pacemaker. He has been well and asymptomatic since the insertion of the pacemaker. In the differential diagnosis of an infant with breath-holding and syncope episodes, when these symptoms in particular cannot be explained by other common reasons, sick sinus syndrome should be kept in mind. This case also illustrates the importance of electrocardiographic studies for the diagnosis. PMID- 11196757 TI - Intraabdominal lymphangiomyoma in an infant with protein-losing enteropathy and hemihypertrophy. AB - Lymphangiomyoma is an extremely rare tumor occurring exclusively in women of reproductive age. The tumor is characterized by proliferation of immature smooth muscle along the lymphatic vessels of the abdomen, thorax and lung. Although lymphangiomyoma has been reported in a young girl and a girl infant, none has been reported in boys. We report herein a case of lymphangiomyoma in a two-year old boy. The unusual presentation in this patient was that the tumor arose from the small bowel mesentery without any evidence of lung involvement. The tumor was extirpated and lymphangiomyomatosis was confirmed pathologically. PMID- 11196758 TI - Polysplenia syndrome with hepatic artery of superior mesenteric artery origin and a circumaortic renal vein. AB - An 8 1/2-month-old girl with biliary atresia and polysplenia syndrome having multiple vascular anomalies without cardiac anomalies is reported. Interruption of the inferior vena cava with azygous continuation, which is a common anomaly, was seen in conjunction with origin of the common hepatic artery from the superior mesenteric artery and with a circumaortic renal vein. The case has particular importance in that no hepatic artery or renal vein variations have been described with biliary atresia and polysplenia syndrome in the literature thus far to our knowledge. The anomalies were shown using different radiological examinations including computed tomography, echocardiography, angiography, venography and magnetic resonance imaging. PMID- 11196759 TI - Preoperative diagnosis of bronchial atresia presenting with recurrent respiratory symptoms in an infant. AB - Bronchial atresia (BA) is a rare respiratory malformation that may be diagnosed from infancy to adulthood. A typical feature of the disease is involvement of the left upper lobe and a mass-like lesion surrounded by a hyperlucent and nondeflating zone. We present a six-month-old male infant who was diagnosed by contrast-enhanced spiral computed tomography (CT) with three-dimensional (3D) technology, and by Tc-99m-macroalbumin aggregate (Tc99m-MAA) radionuclide scintigraphy. We stress that early diagnosis of BA can be made noninvasively using contrast-enhanced spiral CT and radionuclide scintigraphy. 3D computed tomographic reformation allows a more accurate diagnosis as well as a more specific approach to management and follow-up. PMID- 11196760 TI - Are ferric compounds useful in treatment of iron deficiency anemia? AB - The effect of ferric compounds in therapy of iron deficiency anemia is doubtful; however, the absorption of iron is not affected negatively by food or drugs. In our Well Baby Clinic, ferric polymaltose (6 mg/kg/d) was given to 59 infants (Group 1) and ferrous sulphate (same doses) was given to 64 infants (Group 2) (74 +/- 9 d, 70 +/- 7 d, respectively). These infants had iron deficiency anemia, and their therapy was continuous. Ferric polymaltose was not as effective as ferrous sulphate, although it increased hemoglobin and serum iron. Mean corpuscular volume and serum ferritin were not significantly changed after therapy. For this reason, we prefer to use only ferrous salts in therapy. PMID- 11196761 TI - Synthesis and magnetic and structural characterization of the first homoleptic lanthanide beta-ketoiminate. PMID- 11196762 TI - Dual pathways for TiO2 sensitization by Na2[Fe(bpy)(CN)4]. PMID- 11196763 TI - Ligand-centered near-infrared luminescence from lanthanide complexes with chelating nitronyl nitroxide free radicals. PMID- 11196764 TI - Syntheses and characterization of anti-inflammatory dinuclear and mononuclear zinc indomethacin complexes. Crystal structures of [Zn2(indomethacin)4(L)2] (L = N,N-dimethylacetamide, pyridine, 1-methyl-2-pyrrolidinone) and [Zn(indomethacin)2(L1)2] (L1 = ethanol, methanol). AB - The syntheses and spectral and structural characterizations of Zn(II) indomethacin [1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid = IndoH] complexes, as different solvent adducts, have been studied. The complexes are unusual in that both monomeric and dimeric complexes are formed and that this is the first example of the same carboxylato ligand binding via both carboxylate oxygen atoms in monomeric and dimeric Zn(II) complexes. The crystal structures of Zn-Indo complexes with N,N-dimethylacetamide (DMA), pyridine (Py), 1-methyl-2 pyrrolidinone (NMP), EtOH, and MeOH as solvent ligands, [Zn2(Indo)4(DMA)2].2DMA, 1, [Zn2(Indo)4(Py)2].2H2O, 2b, [Zn2(Indo)4(NMP)2], 3, cis-[Zn(Indo)2(EtOH)2], 4, and cis-[Zn(Indo)2(MeOH)2], 5, were determined. Complexes 1, 2b, and 3 crystallize in the triclinic space group P1 (No. 2): a = 13.628(2) A, b = 17.462(2) A, c = 11.078(1) A, alpha = 99.49(1) degrees, beta = 108.13(1) degrees, gamma = 110.10(1) degrees for 1; a = 13.347(3) A, b = 16.499(5) A, c = 10.857(1) A, alpha = 99.48(2) degrees, beta = 108.25(2) degrees, gamma = 106.24(2) degrees for 2; a = 14.143(3) A, b = 14.521(2) A, c = 11.558(2) A, alpha = 109.07(1) degrees, beta = 90.80(2) degrees, gamma = 116.40(1) degrees for 3. The three complexes exhibit dinuclear paddle-wheel structures with a Zn...Zn distance of 2.9686(6) A, Zn-ORCOO distances of 2.035(2)-2.060(2) A, and a Zn-ODMA distance of 1.989(2) A in 1, a Zn...Zn distance of 2.969(1) A, Zn-ORCOO distances of 2.020(3) 2.049(3) A, and a Zn-NPy distance of 2.036(3) A in 2, and a Zn...Zn distance of 2.934(1) A, Zn-ORCOO distances of 2.009(3)-2.051(3) A, and a Zn-ONMP distance of 1.986(3) A in 3. In these cases, the zinc ions are offset along the z direction such that the L-Zn...Zn-L moiety is nonlinear, unlike the Cu analogues. Each Zn has a square-pyramidal geometry bridged by four carboxylato ligands in the basal plane with the solvent ligands containing an O- or N-donor atom at the apex. Complexes 4 and 5 are isostructural, with space group C2/c (No. 15). For 4, a = 30.080(2) A, b = 5.3638(6) A, c = 24.739(2) A, beta = 90.342(7) degrees, and for 5, a = 29.419(2) A, b = 5.320(2) A, c = 24.461(2) A, beta = 90.840(4) degrees. The Zn resides on a 2-fold axis and the complexes have a distorted cis octahedral structure with Zn-ORCOO bond lengths of 2.183(3) and 2.169(3) A, a Zn-OEtOH bond length of 2.015(3) A in 4, Zn-ORCOO bond lengths of 2.195(2) and 2.151(2) A, and a Zn-OMeOH bond length of 2.022(3) A in 5. PMID- 11196765 TI - Reactivity of [RuHCl(PiPr3)2]2 with functionalized vinyl substrates. The H2 ligand as a sensitive probe of electronic structure. AB - Reaction of [RuHClL2]2 (L = PiPr3) with 2-vinylpyridine gives L2ClRu(eta 2 CH=CHC5H4N) with liberation of H2. Reaction of [RuHClL2]2 with a range of olefins D(H)C=CR(EWG) substituted by electron-donating (D) and -withdrawing (EWG) groups occurs by oxidative addition of a vinyl C-H bond to give the metallacycles L2ClHnRu(eta 2-(++)C(D)=CR(EWG)). The 13C chemical shift of ++C and the fate of the "Hn" unit (decoordination, binding as H2, or binding as two hydrides) are strongly correlated, depend on the donating and withdrawing power of D and EWG, and can be used to decide whether ++C binds to Ru as a carbene or as a vinyl. These results emphasize the reducing power of Ru(II) when pi-acid ligands such as CO are absent. PMID- 11196766 TI - A new class of electron-rich unsaturated molecules: Ru2HnX4-n(PiPr3)4, X = anion. AB - Synthesis, spectroscopic, and X-ray structural characterization of Ru2HnCl4-nL4 (n = 2, 3) and Ru2H2F2L4 (L = PiPr3) are reported. The structure of Ru2HCl3L4 is also reported. These are dinuclear species containing two five-coordinate, approximately square-pyramidal metal atoms. Halides, not hydrides, preferentially occupy bridging sites, and the RuXL2 terminal moiety shows limited fluxionality, but hydrides do not migrate between metals. The limited steric protection provided by PiPr3 is evident from the dimerization observed and from the fact that all these structures have rather small [symbol: see text]P-Ru-P (approximately 105 degrees). Also reported are RuHXL2 species with X = acetylacetonate, phenoxide, O3SCH3, and O3SCF3. Several examples of coordinated olefin to complexed carbene conversions are used to test the influence of anion X on reactivity. PMID- 11196767 TI - Tuning charge recombination rate constants through inner-sphere coordination in a copper(I) donor-acceptor compound. AB - The coordination compounds [Cu(bpy-MV2+)(PPh3)2](PF6)3, where bpy-MV2+ is the 1 (4-(4'-methyl-2,2'-bipyridin-4-yl)butyl)-1'-methyl-4, 4'-bipyridinediium(2+) cation, and [Cu(dmb)(PPh3)2](PF6), where dmb is 4,4'-dimethyl-2,2'-bipyridine, have been prepared and characterized. Visible light (417 nm) excitation of [Cu(bpy-MV2+)(PPh3)2]3+ at room temperature leads to rapid intramolecular electron transfer, kcs > 1 x 10(8) s-1, to form a charge-separated state with an electron localized on the pendant viologen group and a copper(II) metal center, abbreviated [CuII-bpy-MV.+]. This state recombines to ground-state products with first-order rate constants that can be tuned with solvent over a approximately 10(7)-10(5) s-1 range. The activation parameters were determined from temperature dependent electron-transfer data with Arrhenius analysis. A model is proposed wherein a solvent molecule is coordinated to Cu(II) in the charge-separated state, [(S)CuII-bpy-MV.+]. Visible light excitation of [Cu(dmb)(PPh3)2](PF6) in argon-saturated dichloromethane produces long-lived photoluminescent excited states, tau = 80 ns, that are dynamically quenched by the addition of Lewis basic solvents. The measured quenching constants each correlate well with the lifetime of the charge-separated state measured after excitation of [Cu(bpy MV2+)(PPh3)2]3+ in the corresponding solvent. PMID- 11196768 TI - Oxalato-bridged dinuclear complexes of Cr(III) and Fe(III): synthesis, structure, and magnetism of [(C2H5)4N]4[MM'(ox)(NCS)8] with MM' = CrCr, FeFe, and CrFe. AB - A new series of homo- and heterometallic oxalato-bridged dinuclear compounds of formulas [Et4N]4[MM'(ox)(NCS)8] ([Et4N]+ = [(C2H5)4N]+; ox = C2O4(2-)) with MM' = Cr(III)-Cr(III) (1), Fe(III)-Fe(III) (2), and Cr(III)-Fe(III) (3) is reported. They have been structurally characterized by infrared spectra and single-crystal X-ray diffraction. The three compounds are isostructural and crystallize in the orthorhombic space group Cmca with Z = 8, a = 16.561(8) A, b = 13.481(7) A, and c = 28.168(8) A for 1, a = 16.515(2) A, b = 13.531(1) A, and c = 28.289(4) A for 2, a = 16.664(7) A, b = 13.575(6) A, and c = 28.386(8) A for 3. The structure of 3 is made up of a discrete dinuclear anion [CrFe(ox)(NCS)8]4- and four disordered [Et4N]+ cations, each of them located on special positions. The anion, in a crystallographically imposed C2h symmetry, contains metal cations in distorted octahedral sites. The Cr(ox)Fe group, which is planar within 0.02 A, presents an intramolecular metal-metal distance of 5.43 A. Magnetic susceptibility measurements indicate antiferromagnetic pairwise interactions for 1 and 2 with J = -3.23 and -3.84 cm-1, respectively, and ferromagnetic Cr-Fe coupling with J = 1.10 cm-1 for 3 (J being the parameter of the exchange Hamiltonian H = -2JS1S2). The ESR spectra at different temperatures confirm the magnetic susceptibility data. PMID- 11196770 TI - Importance of multiple-scattering phenomena in XAS structural determinations of [Ni(CN)4]2- in condensed phases. AB - A quantitative analysis of the XAS spectra of the tetracyanonickelate complex [Ni(CN)4]2- has been carried out. The simultaneous study of the EXAFS and XANES regions yielded complementary information regarding the geometric and electronic structures of the complex. XANES spectra were modeled by applying recently developed self-consistent, full multiple-scattering algorithms in the FEFF8 code (version 8 x 34). XANES spectra for clusters of different sizes (from 9 to 125 atoms) were computed and compared with experimental spectra. This region of the spectra was proportional to a broadened Ni p-density of states diagram above the Fermi level. Although the main features of the XANES spectra were reasonably reproduced by computations, the weak dependence of the theoretical spectra on cluster size contrasts with the close similarity between the experimental spectra of the solid and solution systems. Because of the special geometry of the complex, calculations with polarized light parallel and perpendicular to the molecular plane were carried out, yielding a reasonable reproduction of the experimental data from another report for cluster sizes equal to or higher than 45 atoms. The highly symmetric square planar structure of the complex was found to be responsible for the unusual amplitude of the multiple-scattering (MS) contributions to the EXAFS spectra. Spectra in this region were fitted using the FEFFIT EXAFS analysis program, taking into account only the MS paths that simultaneously have both a high amplitude, as calculated with the ab initio code FEFF, and a small Debye-Waller factor, as estimated by the independent-vibration approximation model. Fitting results yielded very similar structures for the Ni2+ complex in the solid state and in solution, though the larger Debye-Waller factors found for the solid suggest higher static disorder in this state. PMID- 11196769 TI - Ligand substitution behavior of a simple model for coenzyme B12. AB - The ligand substitution reactions of trans-[CoIII(en)2(Me)H2O]2+, a simple model for coenzyme B12, were studied for cyanide and imidazole as entering nucleophiles. It was found that these nucleophiles displace the coordinated water molecule trans to the methyl group and form the six-coordinate complex trans [Co(en)2(Me)L]. The complex-formation constants for cyanide and imidazole were found to be (8.3 +/- 0.7) x 10(4) and 24.5 +/- 2.2 M-1 at 10 and 12 degrees C, respectively. The second-order rate constants for the substitution of water were found to be (3.3 +/- 0.1) x 10(3) and 198 +/- 13 M-1 s-1 at 25 degrees C for cyanide and imidazole, respectively. From temperature and pressure dependence studies, the activation parameters delta H++, delta S++, and delta V++ for the reaction of trans-[CoIII(en)2(Me)H2O]2+ with cyanide were found to be 50 +/- 4 kJ mol-1, 0 +/- 16 J K-1 mol-1, and +7.0 +/- 0.6 cm3 mol-1, respectively, compared to 53 +/- 2 kJ mol-1, -22 +/- 7 J K-1 mol-1, and +4.7 +/- 0.1 cm3 mol-1 for the reaction with imidazole. On the basis of reported activation volumes, these reactions follow a dissociative mechanism in which the entering nucleophile could be weakly bound in the transition state. PMID- 11196771 TI - Hydrothermal synthesis of (C6N2H14)2(UVI2UIVO4F12), a mixed-valent one dimensional uranium oxyfluoride. AB - A new hybrid organic-inorganic mixed-valent uranium oxyfluoride, (C6N2H14)2(U3O4F12), UFO-17, has been synthesized under hydrothermal conditions using uranium dioxide as the uranium source, hydrofluoric acid as mineralizer, and 1,4-diazabicyclo[2.2.2]octane as template. The single-crystal X-ray structure was determined. Crystals of UFO-17 belonged to the orthorhombic space group Cmcm (no. 63), with a = 14.2660(15) A, b = 24.5130(10) A, c = 7.201(2) A, and Z = 4. The structure reveals parallel uranium-containing chains of two types: one type is composed of edge-sharing UO2F5 units; the other has a backbone of edge-sharing UF8 units, each sharing an edge with a pendant UO2F5 unit. Bond-valence calculations suggest the UF8 groups contain UIV, while the UO2F5 groups contain UVI. EXAFS data give results consistent with the single-crystal X-ray structure determination, while comparison of the uranium LIII-edge XANES of UFO-17 with that of related UIV and UVI compounds supports the oxidation-state assignment. Variable-temperature magnetic susceptibility measurements on UFO-17 and a range of related hybrid organic-inorganic uranium(IV) and uranium(VI) fluorides and oxyfluorides further support the formulation of UFO-17 as a mixed-valent UIV/UVI compound. PMID- 11196772 TI - Single-crystal polarized optical absorption spectroscopy of the one-dimensional ferrimagnet MnIICuII(pba)(H2O)3.2H2O (pba = 1,3-propylenebis(oxamato)). AB - Powder and single-crystal optical absorption of the ferrimagnet MnIICuII(pba)(H2O)(3).2H2O (denoted MnCu) and the Mn-doped compound Mn0.1Mg0.9Cu(pba)(H2O)(3).2H2O (denoted Mn0.1Mg0.9Cu) with pba standing for 1,3 propylenebis(oxamato) was investigated in the 10-300 K range. The crystal structure of MnCu was previously reported, and consists of bimetallic chains with octahedral MnII and square pyramidal CuII ions linked by oxamato bridges, MnCu and Mn0.1Mg0.9Cu being isostructural. The spectra of both MnCu and Mn0.1Mg0.9Cu show an important dichroism along the chain direction, due to the strong polarization of the CuII band at around 16,000 cm-1 in this direction. They exhibit narrow and intense spin-forbidden MnII transitions in the 24,000-25,000 cm-1 range, which are activated by an exchange mechanism. The polarization and thermal dependence of the 6A1g-->4A1g, 4Eg(G) MnII transitions were recorded. The polarization along the chain axis was interpreted in the framework of the pair mechanism first introduced by Tanabe and co-workers. A theoretical expression for the thermal dependence of the intensity was derived by considering the CuII spin as a quantum spin and the MnII spin as a classical spin, and compared with the experimental data. The interaction parameter between the local ground states has been found to be J = -25 cm-1 using the spin Hamiltonian H = -J sigma i(SMn,iSCu,i + SMn,i+1SCu,i). The spectra of Mn0.1Mg0.9Cu showed cold and hot bands, whose energy difference is directly related to J and the interaction parameter J* between the CuII ion in its ground state and the MnII ion in its spin-flip excited state. J* has been estimated to be +40 cm-1. These results have been compared to those obtained with other MnIICuII compounds. The complementarity between optical and magnetic properties has been discussed. PMID- 11196773 TI - Synthesis and structures of heterocyclic azidogallanes [(CH3)ClGaN3]4 and [(CH3)BrGaN3]3 en route to [(CH3)HGaN3]x: an inorganic precursor to GaN. AB - The synthesis of [(CH3)ClGaN3]4 (1) with a heterocyclic cyclooctane-like structure and [(CH3)BrGaN3]3 (2) with a trimeric structure has been demonstrated. X-ray structural determinations reveal that 1 and 2 consist of Ga4N4 eight membered rings and Ga3N3 six-membered rings, respectively, in which the Ga atoms are bridged by the alpha nitrogens of the azide groups. [(CH3)ClGaN3]4 crystallizes in the tetragonal space group P42(1)c with a = 11.017(4) A, c = 8.699(7) A, and Z = 8. [(CH3)BrGaN3]3 crystallizes in the triclinic space group P1 with a = 8.1080(10) A, b = 9.9390(13) A, c = 10.4439(13) A, alpha = 86.069(3) degrees, beta = 86.771(3) degrees, gamma = 80.829(2) degrees, and Z = 6. The reaction of 1 and 2 with LiGaH4 yields [(CH3)HGaN3]x, which is a new low temperature source of GaN. PMID- 11196774 TI - 1:1 complexes of dimethylthio- and ethylenedithio-tetrathiafulvalenothioquinone 1,3-dithiolemethides with CuBr2 as a new type of pi/d molecular system. AB - The reaction of dimethylthio- (1) and ethylenedithio tetrathiafulvalenothioquinone-1,3-dithiolemethides (2) with CuBr2 gave 1:1 complexes between the donors and CuBr2, 1.CuBr2 and 2.CuBr2, in which the Cu atom of CuBr2 binds to the thiocarbonyl S atom in 1 and 2. The electrical conductivity (sigma) of 1.CuBr2 at room temperature was ca. 10(-5) S cm-1, while a comparatively high value of 4.0 S cm-1 was obtained for 2.CuBr2, whose temperature dependence of sigma exhibited, however, semiconducting behavior with a very small activation energy of 0.18 eV. The observed paramagnetic susceptibilities (chi p's) of the Cu complexes were composed of both a component due to the localized Cu spins obeying the Curie-Weiss law and a temperature independent chi p due to the conducting pi electrons on the 1- or 2-stacked columns. From the Curie constants obtained, the degrees of intramolecular electron transfer from 1 and 2 to CuBr2 moieties were estimated at ca. 90% and 60%, respectively. The small, negative Weiss temperature suggest very weak antiferromagnetic interactions among the Cu spins on the CuBr2 moieties. PMID- 11196775 TI - Structure and reactivity of aquacarbonylruthenium(II) complexes. An X-ray and oxygen-17 NMR study. AB - The water exchange on [Ru(CO)(H2O-eq)4(H2O-ax)](tos)2 (1), [Ru(CO)2(H2O-eq)2(H2O ax)2](tos)2 (2), and [Ru(CO)3(H2O)3](ClO4)2 (3), the 17O exchange between the bulk water and the carbonyl oxygens have been studied by 17O NMR spectroscopy, and the X-ray crystallographic structures of 1 and 2 have been determined. The water exchange of equatorially and axially coordinated water molecules on 1 and 2 follow an Id mechanism and are characterized by keq298 (s-1), delta H++ (kJ/mol), and delta S++ (J/(mol K)) of (2.54 +/- 0.05) x 10(-6), 111.6 +/- 0.4, and 22.4 +/ 1 (1-eq); (3.54 +/- 0.02) x 10(-2) and 81 (1-ax); (1.58 +/- 0.14) x 10(-7), 120.3 +/- 2, and 28.4 +/- 4 (2-eq); and (4.53 +/- 0.08) x 10(-4), 97.9 +/- 1, and 19.3 +/- 3 (2-ax). The observed reactivities correlate with the strength of the Ru-OH2 bonds, as expressed by their length obtained by X-ray studies: 2.079 (1 eq), 2.140 (1-ax), 2.073 (2-eq), and 2.110 (2-ax) A. 3 is strongly acidic witha pKa of -0.14 at 262 K. Therefore, the acid-dependent water exchange can take place through 3 or Ru(CO)3(H2O)3OH+ with an estimated keq298 of 10(-4)/10(-3) s-1 and kOH262 of 0.053 +/- 0.006 s-1. The 17O exchange rate between the bulk water and the carbonyl oxygens increases from 1 to 2 to 3. For 1 an upper limit of 10( 8) s-1 was estimated. For 2, no acid dependence of kRuCO between 0.1 and 1 m Htos was observed. At 312.6 K, in 0.1 and 1 m Htos, kRuCO = (1.18 +/- 0.03) x 10(-4). For the tricarbonyl complex, the exchange can proceed through 3 or Ru(CO)3(H2O)2OH+ with kRuCO and kRuOHCO of, respectively, 0.003 +/- 0.002 and 0.024 +/- 0.003 s-1, with a ruthenacarboxylic acid intermediate. PMID- 11196777 TI - A dimeric titanium-containing polyoxometalate. Synthesis, characterization, and catalysis of H2O2-based thioether oxidation. AB - The previously unknown titanium(IV)-containing mu-hydroxo dimeric heteropolytungstate (Bu4N)7[(PTiW11O39)2-OH] (TBA salt of H1) has been synthesized, starting from H5PTiW11O40, and characterized by elemental analysis, multinuclear (31P, 17O, 183W) NMR, IR, FAB-MS, cyclic voltammetry, and potentiometric titration. 31P NMR reveals that H1 (delta -12.76) readily forms in MeCN from the Keggin monomer (POM), PTiW11O40(5-) (2, delta -13.34), upon the addition of 1.5 equiv of H+, via the protonated species, P(TiOH)W11O39(4-) (H2, delta -13.44). The ratio of H1, 2, and H2, which are present in equilibrium in MeCN solution at 25 degrees C, depends on the concentration of both H+ and H2O. The Ti-O-Ti linkage readily reacts with nucleophilic reagents, such as H2O and ROH, to yield monomeric Keggin derivatives. mu-Hydroxo dimer H1 shows higher catalytic activity than 2 for thioether oxidation by hydrogen peroxide in acetonitrile. The reaction proceeds readily at room temperature and affords the corresponding sulfoxide and sulfone in ca. quantitative yield. The addition of H2O2 to H1 or H2 results in the formation of a peroxo complex, most likely the hydroperoxo complex P(TiOOH)W11O39(4-) (I), which has 31P NMR resonance at -12.43 ppm. The rate of the formation of I is higher from H2 than from H1. When H1 is used as a catalyst precursor, the rates of the thioether oxidation and peroxo complex formation increase with increasing H2O concentration, which favors the cleavage of H1 to H2. H2O2 in MeCN slowly converts 2 to another peroxotitanium complex, P(TiO2)W11O39(5-) (II), which has 31P NMR resonance at -12.98 ppm. Peroxo complexes I and II differ in their protonation state and interconvert fast on the 31P NMR time scale. Addition of 1 equiv of H+ completely converts II to I, while 1 equiv of OH- completely converts I to II. 31P NMR confirms that I is stable under turnover conditions (thioether, H2O2, MeCN). Contrary to two-phase systems such as dichloroethane/aqueous H2O2, no products resulting from the destruction of the Keggin POM were detected in MeCN in the presence of H2O2 (a 500-fold molar excess). The reactivity of I, generated in situ from II by adding 1 equiv of H+, toward organic sulfides under stoichiometric conditions was confirmed using both 31P NMR and UV-vis spectroscopy. This is a rare demonstration of the direct stoichiometric oxidation of an organic substrate by a titanium peroxo complex. PMID- 11196776 TI - Structural characterization of the picket fence (TpivPP) porphyrins Co(TpivPP), Co(TpivPP)(NO2)(1-MeIm), and Co(TpivPP)(NO2)(1,2-Me2Im). AB - The compounds Co(TpivPP) (1), Co(TpivPP)(NO2)(1-MeIm) (2), and Co(TpivPP)(NO2)(1,2-Me2Im) (3) have been synthesized (TpivPP = meso tetrakis(alpha, alpha, alpha, alpha-o-pivalamidophenyl)porphyrinato dianion), and their structures have been determined with single-crystal X-ray diffraction methods. 1: a = 17.578(1) A, b = 17.596(1) A, c = 20.639(1) A, beta = 115.03(1) degrees, P2(1)/c, Z = 4, T = -120 degrees C. 2: a = 18.522(4) A, b = 18.942(4) A, c = 18.177(4) A, beta = 90.68(3) degrees, C2/c, Z = 4, T = -70 degrees C. 3: a = 18.998(4) A, b = 19.187(4) A, c = 18.000(4) A, beta = 90.96(3) degrees, C2/c, Z = 4, T = -120 degrees C. Compounds 2 and 3 have crystallographically imposed 2-fold axes. In 2 and 3, which represent R-state (relaxed) and T-state (tense) models, respectively, for hemoglobin, the NO2 ligand is bound on the "picket" side to the Co atom, and either 1-MeIm (for 2) or 1,2-Me2Im (for 3) is bound to the Co atom at the sixth coordination site on the sterically unhindered side of the molecule. The average deviations of atoms from the 24-atom porphyrin core are 0.031, 0.129, and 0.117 A for 1, 2, and 3, respectively. The Co atom is -0.043(1) A out of the mean 24-atom porphyrin plane toward the 1-MeIm ligand in 2 and -0.089(1) A out of the plane toward the 1,2-Me2Im ligand in 3. The bonds of both axial ligands in the R-state model 2, 1.898(4) A for Co-N(O2) and 1.995(4) A for Co-N(base), are shorter than the corresponding bonds in the T-state model 3, 1.917(4) A for Co N(O2) and 2.091(4) A for Co-N(base). PMID- 11196778 TI - Synthesis, characterization, and crystal structure of alpha-[Ru(azpy)2(NO3)2] (azpy = 2-(phenylazo)pyridine) and the products of its reactions with guanine derivatives. AB - The synthesis and characterization of alpha-[Ru(azpy)2(NO3)2], 1, are reported (azpy is 2-(phenylazo)pyridine; alpha indicates the isomer in which the coordinating pairs ONO2, N(py), and N(azo) are cis, trans, and cis, respectively). The solid-state structure of 1 has been determined by X-ray crystallography. Crystal data: orthorhombic a = 15.423(5) A, b = 14.034(5) A, c = 10.970(5) A, V = 2374(2) A3, space group P2(1)2(1)2(1) (No. 19), Z = 4, Dcalc = 1.655 g cm-3. The structure refinement converged at R1 = 0.042 and wR2 = 0.118 for 3615 unique reflections and 337 parameters. The octahedral complex shows monodentate coordination of the two nitrate ligands. The Ru-N(azo) bond distances (2.014(4) and 1.960(4) A), slightly shorter than the Ru-N(py) bonds (2.031(4) and 2.059(4) A), agree well with the pi-back-bonding ability of the azo groups. The binding of the DNA-model bases 9-ethylguanine (9egua) and guanosine (guo) to 1 has been studied and compared with previously obtained results for the binding of model bases to the bis(bipyridyl)ruthenium(II) complex. The ligands 9egua and guo appear to form monofunctional adducts, which have been isolated as alpha [Ru(azpy)2(9egua)Cl]PF6, 2, alpha-[Ru(azpy)2(9egua)(H2O)]-(PF6)2, 3, alpha [Ru(azpy)2(guo)(H2O)](PF6)2, 4, and alpha-[Ru(azpy)2(guo)Cl]Cl, 5. The orientations of 9egua and guo in these complexes have been determined in detail with the use of 2D NOESY NMR spectroscopy. In 2 and 5, H8 is directly pointed toward the coordinated Cl, whereas, in 3 and 4, H8 is wedged between the pyridine and phenyl rings. The guanine derivatives in the azpy complexes can have more orientations than found for related cis-[Ru(bpy)2Cl2] species. This fluxionality is considered to be important in the binding of the alpha-bis(2 (phenylazo)pyridine)ruthenium(II) complex to DNA. In complex 1, ruthenium is the chiral center and in the binding to guanosine, two diastereoisomers each of adducts 4 and 5 have been clearly identified by NMR spectroscopy. PMID- 11196779 TI - Magnetic coupling through the carbon skeleton of malonate in two polymorphs of ([Cu(bpy)(H2O)][Cu(bpy)(mal)(H2O)])(ClO4)2 (H2mal = malonic acid; bpy = 2,2' bipyridine). AB - Two polymorphic malonato-bridged copper(II) complexes of formula ([Cu(bpy)(H2O)][Cu(bpy)(mal)(H2O)])-(ClO4)2 (1 and 2) (bpy = 2,2'-bipyridine and mal = malonate dianion) have been prepared and their structures solved by X-ray diffraction methods. Compound 1 crystallizes in the monoclinic space group P2(1)/a, with a = 23.743(3) A, b = 9.7522(5) A, c = 27.731(2) A, beta = 114.580(10) degrees, and Z = 4. Compound 2 crystallizes in the orthorhombic space group Pbcn, with a = 23.700(5) A, b = 25.162(5) A, c = 9.693(5) A, and Z = 4. The structures of 1 and 2 are made up of uncoordinated perchlorate anions and malonate-bridged zigzag copper(II) chains grouped in an isosceles triangle running parallel to the b (1) and c (2) axes. These chains are built by a [Cu(bpy)(mal)(H2O)] unit acting as bis-monodentate ligand toward two [Cu(bpy)(H2O)] adjacent units through its OCCCO skeleton in an anti-anti conformation, whereas the OCO carboxylate bridges exhibit the anti-syn conformation. Compounds 1 and 2 contain four crystallographically independent copper(II) atoms, but the environment of all of them is distorted square pyramidal: the axial position is occupied by a water molecule, whereas the equatorial plane is formed by a chelating bpy and either a bidentate malonate or two carboxylate oxygens from two malonate groups. The equatorial Cu-O(mal) (1.911(4)-1.978(4) (1) and 1.897(5)-1.991(4) A (2)) and Cu-N(bpy) (1.983(4) 2.008(5) (1) and 1.971(6)-2.007(6) A (2)) bonds are somewhat shorter than the axial Cu-O(w) one (2.257(5)-2.524(5) (1) and 2.236(5)-2.505(6) A (2)). The angles subtended at the copper atom by the chelating bpy vary in the ranges 80.9(2) 81.8(2) degrees (1) and 80.4(2)-82.1(2) degrees (2), values which are somewhat smaller than those of the chelating malonate (80.4(2)-82.1(2) degrees (1) and 93.0(2)-93.6(2) degrees (2)). The intrachain copper-copper separations through the OCCCO fragment are 8.227(1) (1) and 8.206(2) A (2), whereas those through the OCO bridging unit are 4.579(1)-5.043(1) (1) and 4.572(2)-5.040(2) A (2). The magnetic behavior of 1 and 2 in the temperature range 2.0-290 K is very close, and it corresponds to an overall ferromagnetic coupling, the chi MT versus T curve exhibiting a maximum at 18 K. The analysis of the magnetic data through a numerical expression derived for the real topology of 1 and 2, that is, chains of isosceles triangles with two intrachain exchange pathways J1 (exchange coupling through the OCO carboxylate) and J2 (exchange coupling through the OCCCO malonate), indicates the occurrence of ferro- (J1 = +4.6 cm-1) and antiferromagnetic couplings (J2 = -4.2 cm-1). The magnetic coupling through these exchange pathways is further analyzed and substantiated by density functional theory calculations on a malonate-bridged trinuclear copper(II) model system. PMID- 11196780 TI - Synthesis, spectroscopic, and structural studies on transition metal complexes involving homoleptic tripodal selenoether and telluroether coordination. AB - The reaction of [MCl2(NCMe)2] (M = Pd or Pt) with 2 molar equiv of MeC(CH2ER)3 (E = Se, R = Me; E = Te, R = Me or Ph) and 2 molar equiv of TlPF6 affords the bis ligand complexes [M(MeC(CH2ER)3)2][PF6]2. The crystal structure of [Pt(MeC(CH2SeMe)3)2][PF6]2 (C16H36F12P2PtSe6, a = 12.272(10) A, b = 18.563(9) A, c = 15.285(7) A, beta = 113.18(3) degrees, monoclinic, P2(1)/n, Z = 4) confirms distorted square planar Se4 coordination at Pt(II), derived from two bidentate tripod selenoethers with the remaining arm not coordinated and directed away from the metal center. Solution NMR studies indicate that these species are fluxional and that the telluroether complexes are rather unstable in solution. The octahedral bis tripod complexes [Ru(MeC(CH2SMe)3)2][CF3-SO3]2 and [Ru(MeC(CH2TePh)3)2][CF3SO3]2 are obtained from [Ru(dmf)6][CF3SO3]3 and tripod ligand in EtOH solution. The thioether complex (C18H36F6O6RuS8, a = 8.658(3) A, b = 11.533(3) A, c = 8.659(2) A, alpha = 108.33(2) degrees, beta = 91.53(3) degrees, gamma = 106.01(2) degrees, triclinic, P1, Z = 1) is isostructural with its selenoether analogue, involving two facially coordinated trithioether ligands in the syn configuration. NMR spectroscopy confirms that this configuration is retained in solution for all of the bis tripod Ru(II) complexes. These low-spin d6 complexes show unusually high ligand field splittings. The hexaselenoether Rh(III) complex [Rh(MeC(CH2SeMe)3)2][PF6]3 was obtained by treatment of [Rh(H2O)6]3+ with 2 molar equiv of MeC(CH2SeMe)3 in aqueous MeOH in the presence of excess PF6- anion, while the iridium(III) analogue [Ir(MeC(CH2SeMe)3)2][PF6]3 was obtained via the reaction of the Ir(I) precursor [IrCl(C8H14)2]2 with the selenoether tripod in MeOH/aqueous HBF4. NMR studies reveal different invertomers in solution for both the Rh and Ir species. The Cu(I) complexes [Cu(MeC(CH2ER)3)2]PF6 were obtained from [Cu(NCMe)4]PF6 and tripod ligand in CH2Cl2 solution. The corresponding Ag(I) species [Ag(MeC(CH2TeR)3)2]CF3SO3 (R = Me or Ph) were obtained from Ag[CF3SO3] and tripod telluroether. In contrast, a similar reaction with 2 molar equiv of MeC(CH2SeMe)3 afforded only the 1:1 complex [Ag(MeC(CH2SeMe)3)]CF3SO3. The structure of this species (C9H18AgF3O3SSe3, a = 8.120(3) A, b = 15.374(3) A, c = 14.071(2) A, beta = 93.86(2) degrees, monoclinic, P2(1)/n, Z = 4) reveals a distorted trigonal planar geometry at Ag(I) derived from one bidentate selenoether and one monodentate selenoether. These units are then linked to adjacent Ag(I) ions to give a one dimensional linear chain cation. PMID- 11196781 TI - Sterically encumbered systems for two low-coordinate phosphorus centers. AB - Tetraarylphenyls of the form 2,3,5,6-Ar4C6 (Ar = p-tert-butylphenyl) are investigated as sterically demanding ligands for the syntheses of compounds having two p-phenylene-bridged phosphorus centers. The precursor to such materials, 1,4-diiodo-2,3,5,6-tetrakis(p-tert-butylphenyl)benzene (1), is readily obtained via a one-pot procedure in 68% yield. Compound 1 is then used to provide the bis(dichlorophosphine) 1,4-bis(dichlorophosphino)-2,3,5,6-tetrakis(p-tert butylphenyl)benzene (2) and the derived bis(phosphine) 1,4-bis(phosphino)-2,3,5,6 tetrakis(p-tert-butylphenyl)benzene (3) in yields of 56 and 94% respectively. These materials provide access to novel materials containing two low-coordinate phosphorus centers bridged by a sterically encumbered phenylene unit. Compound 2 reacts with benzaldehyde and 2,6-dichlorobenzaldehyde in the presence of excess trimethylphosphine and zinc to produce the new pale yellow crystalline bis(phosphaalkenes) (E,E)-PhC(H)=PAr4C6P=C(H)Ph (4a; 42%) and (E,E) Ar'C(H)=PAr4C6P=C(H)Ar' (4b; 46%; Ar' = 2,6-dichlorophenyl). The crystal structure of 4a shows a P=C bond length of 1.676(5) A. Compound 2 is also used to provide the unusual red-orange bis(diphosphene) DmpP=PAr4C6P=PDmp (5; 55%; Dmp = 2,6-Mes2C6H3). Compound 5 is structurally characterized, and a P=P bond length of 2.008(2) A is ascertained. PMID- 11196782 TI - The flash-quench technique in protein-DNA electron transfer: reduction of the guanine radical by ferrocytochrome c. AB - Electron transfer from a protein to oxidatively damaged DNA, specifically from ferrocytochrome c to the guanine radical, was examined using the flash-quench technique. Ru(phen)2dppz2+ (dppz = dipyridophenazine) was employed as the photosensitive intercalator, and ferricytochrome c (Fe3+ cyt c), as the oxidative quencher. Using transient absorption and time-resolved luminescence spectroscopies, we examined the electron-transfer reactions following photoexcitation of the ruthenium complex in the presence of poly(dA-dT) or poly(dG-dC). The luminescence-quenching titrations of excited Ru(phen)2dppz2+ by Fe3+ cyt c are nearly identical for the two DNA polymers. However, the spectral characteristics of the long-lived transient produced by the quenching depend strongly upon the DNA. For poly(dA-dT), the transient has a spectrum consistent with formation of a [Ru(phen)2dppz3+, Fe2+ cyt c] intermediate, indicating that the system regenerates itself via electron transfer from the protein to the Ru(III) metallointercalator for this polymer. For poly(dG-dC), however, the transient has the characteristics expected for an intermediate of Fe2+ cyt c and the neutral guanine radical. The characteristics of the transient formed with the GC polymer are consistent with rapid oxidation of guanine by the Ru(III) complex, followed by slow electron transfer from Fe2+ cyt c to the guanine radical. These experiments show that electron holes on DNA can be repaired by protein and demonstrate how the flash-quench technique can be used generally in studying electron transfer from proteins to guanine radicals in duplex DNA. PMID- 11196783 TI - Syntheses, structures, and reactivities of heteroleptic magnesium amide thiolates. AB - The syntheses and characterizations of a family of novel heteroleptic magnesium amide thiolates are presented. The compounds are synthesized by ligand redistribution chemistry involving reactions of equimolar amounts of magnesium amides and magnesium thiolates. Utilization of the smaller thiolates [Mg(SPh)2]n and [Mg(S-2,4,6-iPr3C6H2)2]n results in the isolation of dimeric species, [Mg(THF)(N(SiMe3)2)(mu-SR)]2 (R = Ph (1), 2,4,6-iPr3C6H2 (2)), with four coordinate metal centers and bridging thiolate functions. The sterically more encumbered thiolate S-2,4,6-tBu3C6H2 induces the formation of the four coordinate, monomeric species Mg(THF)2(N(SiMe3)2)(S-2,4,6-tBu3C6H2) (3)). Careful choice of reaction conditions allows the successful syntheses of pure heteroleptic compounds; however, it remains difficult to obtain the compounds in high yields, since a tendency toward product symmetrization and ligand redistribution under re-formation of the starting materials is prevalent. One of these symmetrized products is also included in this report: the dimeric, four coordinate magnesium thiolate [Mg-(THF)(S-2,4,6-tBu3C6H2)(mu-S-2,4,6-tBu3C6H2)]2 (4), isolated as the product of the reaction between [Mg-(N(SiMe3)2)2]2 and Mg(THF)2(S-2,4,6-tBu3C6H2)2. All compounds were characterized by NMR and IR spectroscopy, elemental analyses, and X-ray crystallography. Crystal data obtained with Mo K alpha (lambda = 0.710 73 A) radiation are as follows. 1: C16H31MgNOSSi2, a = 11.2100(1) A, b = 17.4512(3) A, c = 11.2999(2) A, beta = 97.952(1) degrees, V = 2189.32(6) A3, Z = 4, monoclinic, space group P2(1)/n, R1 (all data) = 0.0934. 2: C25H49MgNOSSi2, a = 11.1691(1) A, b = 11.0578(1) A, c = 26.0671(4) A, beta = 99.906(1) degrees, V = 3171.44(6) A3, Z = 4, monoclinic, space group P2(1)/c, R1 (all data) = 0.0557. 3: C36H71MgNO3SSi2, a = 42.8293(16) A, b = 10.9737(5) A, c = 16.8305(7) A, beta = 98.755(3) degrees, V = 7818.1(6) A3, Z = 8, monoclinic, space group C2/c, R1 (all data) = 0.1331. 4: C80H132Mg2O2S4, a = 18.8806(2) A, b = 19.3850(2) A, c = 27.3012(4) A, beta = 97.250(1) degrees, V = 9912.4(2) A3, Z = 4, monoclinic, space group P2(1)/n, R1 (all data) = 0.1023. PMID- 11196784 TI - Interaction of oxo-bridged vanadium(III) phenanthroline and bipyridine dimers with DNA. AB - Cationic mu-oxo V(III) dimers of the type [V2OL4Cl2]2+ (L = 1,10-phenanthroline, 3,4,7,8-tetramethyl-1,10-phenanthroline, 4,7-diphenyl-1,10-phenanthroline; or 2,2'-bipyridine) are shown to interact very strongly with DNA and to lead ultimately to its degradation. Spectroscopic binding studies, electrophoreses, DNA melting temperature experiments, and other tests on the parent 1,10 phenthroline complex all yield results consistent with tight binding. However, the exact nature of the binding--i.e., intercalative, groove binding, electrostatic, or covalent--remains unclear. Resonance Raman spectroscopy is found to be a powerful method for studying the interaction of these mu-oxo V(III) dimers with DNA and shows that in frozen aqueous solution, the parent complex [V2O(phen)4Cl2]2+ undergoes initial aquation, followed by the reaction of the aquated species with the DNA. Once the V(III) dimer is bound to the DNA, redox takes place, leading to the formation of alkaline-sensitive lesions. Hydrogen peroxide is implicated as a partner in this redox event, based on the effects of the enzymes SOD and catalase. PMID- 11196785 TI - Adduct formation or metathesis reactions of silver complexes containing the fluorinated ligands [HB(3,5-(CF3)2Pz)3]- and [CF3SO3]-: formation of silver adducts containing unsupported silver-germanium bonds. AB - A mixture of [HB(3,5-(CF3)2Pz)3]Ag(eta 2-toluene) and [(Me)2ATI]GeCl in CH2Cl2, rather than undergoing metathesis, formed a 1:1 adduct [HB(3,5-(CF3)2Pz)3]Ag<- GeCl[(Me)2ATI] (1, where [HB(3,5-(CF3)2Pz)3] = hydrotris(3,5 bis(trifluoromethyl)pyrazolyl)borate and [(Me)2ATI] = N-methyl-2 (methylamino)troponiminate) featuring a silver-germanium bond. Solutions of 1 (in CH2Cl2 or toluene) did not precipitate AgCl even after several days. However, it easily underwent metathesis with CF3SO3Ag, leading to the chloride-free product [HB(3,5-(CF3)2Pz)3]Ag<--Ge(OSO2CF3)[(Me)2ATI] (2). Compounds 1 and 2 were characterized by X-ray crystallography. The Ag-Ge bond distances of 1 and 2 are 2.4215(9) and 2.4116(10) A, respectively. PMID- 11196786 TI - Copper and silver complexes containing organic azide ligands: syntheses, structures, and theoretical investigation of [HB(3,5-(CF3)2Pz)3]CuNNN(1-Ad) and [HB(3,5-(CF3)2Pz)3]AgN(1-Ad)NN (where Pz = pyrazolyl and 1-Ad = 1-adamantyl). AB - Treatment of [HB(3,5-(CF3)2Pz)3]Na(THF) with CF3SO3Cu followed by 1 azidoadamantane affords [HB(3,5-(CF3)2Pz)3]CuNNN(1-Ad) in 65% yield. The solid state structure shows that the copper atom is coordinated to the terminal nitrogen atom (NT) of the azidoadamantane ligand. The related silver(I) adduct can be prepared in 80% yield by the treatment of [HB(3,5-(CF3)2Pz)3]Ag(THF) with 1-azidoadamantane. However, [HB(3,5-(CF3)2Pz)3]AgN(1-Ad)NN shows a different bonding mode where the silver atom coordinates to the alkylated nitrogen atom (NA) of the azidoadamantane ligand. Asymmetric stretching bands of the azido group for copper and silver adducts appear at 2143 and 2120 cm-1, respectively. Theoretical investigation shows that steric effects do not play a dominant role in determining the bonding mode of the azide ligand in these two metal complexes. Although the copper(I) ion affinity for the two coordinating sites NT and NA is nearly identical, copper-azide back-bonding interactions favor the copper-NT mode of bonding over the copper-NA mode. Silver (a very poor back-bonding metal) prefers the NA site for coordination. The NA site has a significantly higher proton affinity and slightly higher sodium ion affinity. Important structural parameters for [HB(3,5-(CF3)2Pz)3]CuNNN(1-Ad) and [HB(3,5-(CF3)2Pz)3]AgN(1-Ad)NN are as follows: Cu-NT 1.861(3) A, NT-N 1.136(4) A, N-NA 1.219(4) A, NT-N-NA 173.1(3) degrees; Ag-NA 2.220(5) A, NT-N 1.143(12) A, N-NA 1.227(10) A, NT-N-NA 176.8(12) degrees. Overall, the azidoadamantane ligand does not undergo any significant changes upon coordination to Cu(I) or Ag(I) ions. PMID- 11196787 TI - Symmetry of metal chelates. AB - Is a metal chelate symmetric, with the motion of the metal described by a single well potential, or is it asymmetric, in a double-well potential? For hydrogen, this is the familiar question of the symmetry of a hydrogen bond. The molecular symmetry of MLn complexes (M = Li, Na, K, Al, Pd, Rh, Si, Sn, Ge, Sb, etc.; L is the anion of 3-hydroxy-2-phenylpropenal) in solution is now probed with the method of isotopic perturbation of equilibrium. A statistical mixture of 3 hydroxy-2-phenylpropenal-d0, -1-d, and -1,3-d2 was synthesized and converted to various metal complexes. Some complexes show two aldehydic signals, which means that their ligands are monodentate. For LiL, NaL, and KL, the 13C NMR isotope shifts, delta CH(D) - delta CH(H), for the aldehydic CH groups are small and negative, consistent with L- being a resonance hybrid. They are small and positive for AlL3, PdL2, Rh(CO)2L, SiX3L, SiL3+X-, (CF3)3GeL, SbCl4L, (EtO)4TaL, and (EtO)4NbL. The positive isotope shifts are unusual, but since they are small and temperature independent, they are intrinsic and indicate that these metal chelates are symmetric, as expected. Large positive isotope shifts, up to 400 ppb, are observed for Ph3GeL, Me3GeL, Ph2GeL2, Bu3SnL, and Ph4SbL. However, it is likely that these are monodentate complexes undergoing rapid metal migration, as judged from the X-ray crystal structures of Ph3SnL and Ph4SbL. NMR experiments indicate an intermolecular mechanism for exchange, which may be a biomolecular double metal transfer. It is remarkable that the isotope shifts in these five complexes demonstrate that they are asymmetric structures, even though they appear from other NMR evidence to be symmetric chelates. PMID- 11196788 TI - Resonance Raman and semiempirical electronic structure studies of an odd-electron dinickel tetraiminoethylenedimacrocycle complex. AB - Resonance Raman studies of Ni2TIED3+ (TIED = tetraiminoethylenedimacrocycle) reveal that many modes couple to the intense electronic transition centered at 725 nm, a feature that is nominally similar to the intense delocalized intervalence absorption bands observed in the same region for Fe2(TIED)L4(5+) and Ru2(TIED)L4(5+) (L is any of several axial ligands). Time-dependent spectral modeling of the Raman and absorption spectra for the nickel compound was undertaken to understand the electronic transition. We were unable to model the Raman and absorption spectra successfully with a single electronic transition, suggesting that the absorption band is made up of two overlapping transitions. Semiempirical electronic structure calculations corroborate the suggestion. Additionally, these calculations indicate that the transitions are in fact ligand localized transitions, with little metal involvement and no charge-transfer character. Furthermore, the ground-state electronic structure is best described as an identical pair of NiII centers bridged by a radical anion rather than a three-site mixed-valence assembly. Previous EPR studies (McAuley and Xu, Inorg. Chem. 1992, 31, 5549) had indicated primarily ligand character for the radical. The assignments are consistent with the resonance Raman results where the dominant modes coupled to the transitions are assigned as totally symmetric bridge vibrations. PMID- 11196790 TI - The first mixed-valence fluorotin alkoxides: new sol-gel precursors of fluorine doped tin oxide materials. PMID- 11196789 TI - Crystal structures and solution behavior of paramagnetic divalent transition metal complexes (Fe, Co) of the sterically encumbered tridentate macrocycles 1,4,7-R3-1,4,7-triazacyclononane: coordination numbers 5 (R = i-Pr) and 6 (R = i Bu). AB - The coordination chemistry of the sterically hindered macrocyclic triamines, 1,4,7-R3-1,4,7-triazacyclononane (R = i-Pr, i-Pr3tacn, and R = i-Bu, i-Bu3tacn) with divalent transition metals has been investigated. These ligands form a series of stable novel complexes with the triflate salts MII(CF3SO3)2 (M = Fe, Co, or Zn) under anaerobic conditions. The complexes Fe(i-Pr3tacn)(CF3SO3)2 (2), [Co(i-Pr3tacn)(SO3CF3)(H2O)](CF3SO3) (3), [Co(i-Pr3tacn)(CH3CN)2](BPh4)2 (4), Zn(i-Pr3tacn)(CF3SO3)2 (5), [Fe(i-Bu3tacn)(CH3CN)2(CF3SO3)](CF3SO3) (6), Fe(i Bu3tacn)-(H2O)(CF3SO3)2 (7), and Co(i-Bu3tacn)(CF3SO3)2 (8) have been isolated. The behavior of these paramagnetic complexes in solution is explored by their 1H NMR spectra. The solid-state structures of four complexes have been determined by X-ray single-crystal crystallography. Crystallographic parameters are as follows. 2: C17H33F6FeN3O6S2, monoclinic, P2(1)/n, a = 10.895(1) A, b = 14.669(1) A, c = 16.617(1) A, beta = 101.37(1) degrees, Z = 4. 3: C17H35CoF6N3O7S2, monoclinic, P2(1)/c, a = 8.669(2) A, b = 25.538(3) A, c = 12.4349(12) A, beta = 103.132(13) degrees, Z = 4. 6: C24H45F6FeN5O6S2, monoclinic, P2(1)/c, a = 12.953(6) A, b = 16.780(6) A, c = 15.790(5) A, beta = 96.32(2) degrees, Z = 4. 7: C20H41F6FeN3O7S2, monoclinic, C2/c, a = 22.990(2) A, b = 15.768(2) A, c = 17.564(2) A, beta = 107.65(1) degrees, Z = 8. The ligand i-Pr3tacn leads to complexes in which the metal ions are five-coordinate, while it's isobutyl homologue affords six-coordinate complexes. This difference in the stereochemistries around the metal center is attributed to steric interactions involving the bulky alkyl appendages of the macrocycles. PMID- 11196791 TI - Synthesis of bis-thiolato-bridged ru(III) dimers. The crystal structure of [Ru(H2edta)(mu-SC6H5)]2. PMID- 11196792 TI - Synthesis and characterization of chelating triamide complexes of bismuth and antimony. PMID- 11196793 TI - A new structural class of lanthanide carbonates: synthesis, properties, and X-ray structure of the one-dimensional chain complex [Co(NH3)6]6[K2(H2O)10] [Nd2(CO3)8](2)20H2O. PMID- 11196794 TI - Oxidative additions of cyclo-octasulfur and cyclo-octaselenium to the cobalt(II) complex of 1,3-bis(dimethylphosphino)propane (dmpp): crystal structures and spectroscopic properties of [Co(S2O)(dmpp)2]PF6 and [Co(Se2)(dmpp)2]BF4. PMID- 11196795 TI - Bimetallic Pt/Ru complexes as catalysts for the electrooxidation of methanol. PMID- 11196796 TI - Neutral macrocycles via halide-induced ring opening of binuclear condensed intermediates. PMID- 11196797 TI - Preparation of a chiral, 2-dimensional network containing metallacrown and copper benzoate building blocks. PMID- 11196798 TI - Novel biomimetic calix[6]arene-based copper(II) complexes. PMID- 11196799 TI - Novel photoisomerization behavior of Rh binuclear complexes involving an azobenzene-bridged bis(terpyridine) ligand. Strong effects of counterion and solvent and the induction of redox potential shift. PMID- 11196800 TI - (Tetrakis(2-pyridylmethyl)ethylenediamine)iron(II) perchlorate. Study of density functional methods. AB - On the basis of the data obtained by X-ray diffraction, the properties of two independent crystallographic subsystems in the [Fe(tpen)](ClO4)2.2/3H2O complex are studied in detail with the density functional method B3LYP. The energies of singlet, triplet, and quintet states at different temperatures are obtained, the influences of geometry on energy changes are analyzed, the regularity of the spin state interconversions is investigated, and the effect of the triplet and action of the anion on spin crossover are discussed. This investigation demonstrates that (1) the energy difference between the high-spin state and singlet state decreases as the Fe-N distance and geometric distortion increase, (2) the spin equilibrium system is predominantly in low-spin form below room temperature and the proportion of high-spin state rapidly increases above room temperature, (3) one of the two cation sites has a greater presence of the high-spin content, (4) the triplet state may be responsible for the fast rate of spin-state interconversions, and (5) the B3LYP method proves to be very adequate to study the spin-state transition of this complex. PMID- 11196801 TI - Infrared and Raman spectroscopic investigations of the Nb(V) fluoro and oxofluoro complexes in the LiF-NaF-KF eutectic melt with development of a diamond IR cell. AB - A vacuum-tight cell for infrared spectroscopic investigations of extremely corrosive melts, e.g., molten fluorides, has been constructed and tested up to 750 degrees C. The cell has a gold-lined sample chamber and a diamond window transparent for the infrared light. It can be furnished with a gold piston that enables the recording of short-path-length FTIR spectra of liquid samples. Solutions of Nb(V) in LiF-NaF-KF eutectic (FLINAK) with and without oxide additions have been investigated by FTIR and Raman spectroscopy. The presence of NbF7(2-), NbOF5(2-), and NbO2F4(3-) complexes was established in the molten state at 600 degrees C. After solidification NbF7(2-) was still the only Nb(V) all fluoro complex present. Three oxofluoro complexes, NbOF6(3-), NbOF5(2-), and NbO2F4(3-), have been identified in the solid state. Typical frequency regions for the different complexes are established. Finally, it was shown that K2NbF7 can be used as an indicator to determine the oxide content of the sample melts. PMID- 11196802 TI - Mixed-addenda vanadium-substituted polyfluorooxometalates: synthesis, characterization, and catalytic aerobic oxidation. AB - For the first time, mixed-addenda vanadium-substituted polyfluorooxometalates, PFOMs, have been synthesized. Depending on the workup procedure used, two types of compounds were prepared. The first PFOM was a quasi Wells--Dawson type compound, [H2F6NaVVW17O56]8-, and the second a mixture of vanadium-substituted polyfluorooxometalates of the Keggin structure, XVIVW11FnO40 - n (X = H2, V, W; n = 1-4). From the X-ray diffraction analysis, [H2F6NaVVW17O56]8- has an elliptic (egg) shape with a central sodium atom surrounded by six fluorine atoms in a trigonal prism coordination. One may differentiate between two types of addenda atoms to be found in belt and capped positions. According to 1H, 19F, and 51V NMR analysis, it is concluded that vanadium is isomorphically substituted in both the belt and capped position of [H2F6NaVVW17O56]8-. The mixture of vanadium substituted PFOMs of the Keggin structure was shown, by HPLC and ESR, to contain at least two species of different charge and of a different vanadium environment. The [H2F6NaVVW17O56]8- PFOM was active for the catalytic aerobic oxidation of alkyl aromatic compounds in biphasic (water-catalyst and substrate) media. The reaction selectivity (autoxidation versus oxydehydrogenation) depended on the substrate and reaction conditions such as temperature and oxygen pressure. The selectivity to oxydehydrogenation was significantly higher compared to the prototypical cobalt acetate catalytic system. PMID- 11196803 TI - Determination of metal-ligand stoichiometries for inorganic complexes using total reflection X-ray fluorescence. AB - The methods usually used to determine the ratio metal-ligand in inorganic complexes require a set of solutions with different concentrations for both the ligand and metal. We propose a new method using the total reflection X-ray fluorescence technique, in which the ratio between metal and ligand is determined precisely, easily, and quickly. Experimental results provide evidence that for different chemical complexes, the ligand-metal ratio determined by this technique deviates at most from stoichiometric values by 6%. The technique is restricted usually to elements with Z above 14, and its detection limit is on the order of 10(-8) g/g. PMID- 11196804 TI - NMR and EPR investigations of iron corrolates: iron(III) corrolate pi cation radicals or iron(IV) corrolates? AB - The chloroiron corrolates of 2,3,7,8,12,13,17,18-octamethyl- and 7,13-dimethyl 2,3,8,12,17,18-hexaethylcorrole ([(Me8C)FeCl] and [(7,13-Me2Et6C)FeCl], respectively) and their bisimidazole complexes have been investigated by NMR spectroscopy as a function of temperature, and by EPR spectroscopy at 4.2 K. Magnetic susceptibilities were measured by the modified Evans method. It is found that the electron configuration of the chloroiron corrolates is that of a S = 3/2 Fe(III) center coupled to a corrolate pi radical, where one electron has been removed from the pi system of the corrolate. This pi radical is antiferromagnetically coupled to the unpaired electrons of the iron to yield an overall S = 1 complex, as evidenced by the very large positive shifts of the meso H resonances (183 and 172 ppm). That this antiferromagnetic coupling is very strong is supported by the near-Curie behavior of the 1H chemical shifts. For the chloroiron corrolates in the presence of imidazole, imidazole-d4, and N methylimidazole at temperatures of -50 degrees C and below, the mono- and bisligand complexes are formed. The NMR spectra can be assigned on the basis of chemical exchange between the chloroiron(III) parent complex and the bisligand complex at -30 degrees C, and between the bisligand complex and the monoligand complex at -50 degrees C. The bisimidazole complexes show pyrrole CH2 and CH3 resonances characteristic of low-spin Fe(III) centers (S = 1/2), but with strongly upfield-shifted meso-H resonances (delta values of -95 and -82.5 ppm for the octamethyl complex and -188 and -161 ppm for the dimethylhexaethyl complex at 203 K) characteristic of the presence of a macrocycle-centered unpaired electron. The magnetic moments of these bisligand complexes are somewhat lower than expected for overall S = 1 systems, and decrease as the temperature is lowered. The lower apparent magnetic moments (2.0-1.8 mu B between -50 and -90 degrees C) are believed to be caused by a combination of weak or no magnetic coupling between the metal and macrocycle electrons and decreasing solubility of the complex as the temperature is lowered. The non-Curie behavior of the 1H chemical shifts observed in the low-temperature (-50 to -90 degrees C) NMR spectra likely arises from a combination of the effects of weak antiferromagnetic coupling of metal and macrocycle spins, a low-lying electronic excited state, and ligand binding/loss equilibria at the highest temperatures studied (-50 degrees C). PMID- 11196805 TI - Crystal structures of a family of silver cyanide complexes of thiourea and substituted thioureas. AB - The syntheses and crystal structures of a family of silver cyanide complexes of thiourea and substituted thioureas are reported. The sulfur ligands include thiourea (tu), 1-methyl-2-thiourea (mtu), 1,3-dimethyl-2-thiourea (dmtu), 1,1,3,3 tetramethyl-2-thiourea (tmtu), and 2-imidazolidinethione (N,N'-ethylenethiourea, etu). Synthesis was effected by dissolving AgCN in an aqueous solution of ligand. Two different complexes were obtained by the reaction of AgCN with tu. Complex 1a: (AgCN)(tu), monoclinic, P2(1)/c, a = 9.3851 (6) A, b = 8.2782 (5) A, c = 7.1178 (5) A, beta = 94.591 (1) degree, and Z = 4. Complex 1b: (AgCN)(tu)2, triclinic, P1, a = 7.9485 (14) A, b = 9.431 (2) A, c = 12.771 (2) A, alpha = 85.695 (3) degrees, beta = 81.210 (4) degrees, gamma = 77.987 (2) degrees, and Z = 4. Complex 2: (AgCN)(mtu), triclinic, P1, a = 4.113 (2) A, b = 9.472 (4) A, c = 9.679 (4) A, alpha = 113.918 (5) degrees, beta = 98.188 (6) degrees, gamma = 97.725 (6) degrees, and Z = 2. Complex 3 (AgCN)2(dmtu)2, monoclinic, P2(1)/m, a = 7.1482 (7) A, b = 14.776 (2) A, c = 7.3366 (7) A, beta = 92.418 (2) degrees, and Z = 2. Complex 4: (AgCN)(tmtu), orthorhombic, P2(1)2(1)2(1), a = 8.823(6) A, b = 10.209 (2) A, c = 10.362 (2) A, and Z = 4. Complex 5: (AgCN)2(etu)2, triclinic, P1, a = 6.8001 (2) A, b = 8.6154 (1) A, c = 13.4747 (3) A, alpha = 71.720 (1) degree, beta = 79.906 (1) degree, gamma = 75.885 (2) degrees, and Z = 2. All of the structures involve either one- or two-dimensional polymeric arrays held together by bridging S and CN groups. There is, however, no similarity between any two of the arrays. Four of the five ligands used also form similar complexes with CuCN. For one ligand, tmtu, the structures are isomorphous. For the other three, not only are the structures not isomorphous, the m/n ratio in (MCN)mLn when M is Ag is different from that when M is Cu. PMID- 11196806 TI - Vanadium complexes of the N(CH2CH2S)3(3-) and O(CH2CH2S)2(2-) ligands with coligands relevant to nitrogen fixation processes. AB - Vanadium(III) and vanadium(V) complexes derived from the tris(2 thiolatoethyl)amine ligand [(NS3)3-] and the bis(2-thiolatoethyl)ether ligand [(OS2)2-] have been synthesized with the aim of investigating the potential of these vanadium sites to bind dinitrogen and activate its reduction. Evidence is presented for the transient existence of (V(NS3)(N2)V(NS3), and a series of mononuclear complexes containing hydrazine, hydrazide, imide, ammine, organic cyanide, and isocyanide ligands has been prepared and the chemistry of these complexes investigated. [V(NS3)O] (1) reacts with an excess of N2H4 to give, probably via the intermediates (V(NS3)(NNH2) (2a) and (V(NS3)(N2)V(NS3) (3), the V(III) adduct [V(NS3)(N2H4)] (4). If 1 is treated with 0.5 mol of N2H4, 0.5 mol of N2 is evolved and green, insoluble [(V(NS3))n] (5) results. Compound 4 is converted by disproportionation to [V(NS3)(NH3)] (6), but 4 does not act as a catalyst for disproportionation of N2H4 nor does it act as a catalyst for its reduction by Zn/HOC6H3Pri2-2,6. Compound 1 reacts with NR1(2)NR2(2) (R1 = H or SiMe3; R2(2) = Me2, MePh, or HPh) to give the hydrazide complexes [V(NS3)(NNR2(2)] (R2(2) = Me2, 2b; R2(2) = MePh, 2c; R2(2) = HPh, 2d), which are not protonated by anhydrous HBr nor are they reduced by Zn/HOC6H3Pri2-2,6. Compound 2b can also be prepared by reaction of [V(NNMe2)(dipp)3] (dipp = OC6H3Pri2-2,6) with NS3H3. N2H4 is displaced quantitatively from 4 by anions to give the salts [NR3(4)][V(NS3)X] (X = Cl, R3 = Et, 7a; X = Cl, R3 = Ph, 7b; X = Br, R3 = Et, 7c; X = N3, R3 = Bu(n), 7d; X = N3, R3 = Et, 7e; X = CN, R3 = Et, 7f). Compound 6 loses NH3 thermally to give 5, which can also be prepared from [VCl3(THF)3] and NS3H3/LiBun. Displacement of NH3 from 6 by ligands L gives the adducts [V(NS3)(L)] (L = MeCN, nu CN 2264 cm-1, 8a; L = ButNC, nu NC 2173 cm-1, 8b; L = C6H11NC, nu NC 2173 cm-1, 8c). Reaction of 4 with N3SiMe3 gives [V(NS3)(NSiMe3)] (9), which is converted to [V(NS3)(NH)] (10) by hydrolysis and to [V(NS3)(NCPh3)] (11) by reaction with ClCPh3. Compound 10 is converted into 1 by [NMe4]OH and to [V(NS3)NLi(THF)2] (12) by LiNPri in THF. A further range of imido complexes [V(NS3)(NR4)] (R4 = C6H4Y-4 where Y = H (13a), OMe (13b), Me (13c), Cl (13d), Br (13e), NO2 (13f); R4 = C6H4Y-3, where Y = OMe (13g); Cl (13h); R4 = C6H3Y2-3,4, where Y = Me (13i); Cl (13j); R4 = C6H11 (13k)) has been prepared by reaction of 1 with R4NCO. The precursor complex [V(OS2)O(dipp)] (14) [OS2(2-) = O(CH2CH2S)2(2-)] has been prepared from [VO(OPri)3], Hdipp, and OS2H2. It reacts with NH2NMe2 to give [V(OS2)(NNMe2)(dipp)] (15) and with N3SiMe3 to give [V(OS2)(NSiMe3)(dipp)] (16). A second oxide precursor, formulated as [V(OS2)1.5O] (17), has also been obtained, and it reacts with SiMe3NHNMe2 to give [V(OS2)(NNMe2)(OSiMe3)] (18). The X-ray crystal structures of the complexes 2b, 2c, 4, 6, 7a, 8a, 9, 10, 13d, 14, 15, 16, and 18 have been determined, and the 51V NMR and other spectroscopic parameters of the complexes are discussed in terms of electronic effects. PMID- 11196807 TI - Solid-state and solution structure of lanthanide complexes of a new nonadentate tripodal ligand containing phenanthroline binding units. AB - The new nonadentate tripodal ligand trenphen (tris[(1,10-phenanthroline-2 carboxamido)-ethyl]amine) has been synthesized by condensation of tren [tris(2 aminoethyl)amine] with an excess of 1,10-phenanthroline-2-carboxylic acyl chloride. The ligand trenphen and its lanthanide complexes (Sm, Nd, Eu, Tb, and Lu) have been structurally characterized by single-crystal X-ray diffractometry. Crystals of trenphen.H2O.CH3CN, 1, are monoclinic, space group P2(1)/n, a = 14.9923(8) A, b = 17.4451(10) A, c = 17.1880(10) A, beta = 114.8290(10) degrees, V = 4079.9(4) A3, Z = 4. The solid-state crystal structures of the isostructural [Ln(trenphen)](OTf)3.yH2O.xEt2O.zCH3CN (OTf = CF3SO3) (Ln = Nd, y = 0.5, x = 1, z = 3 (2); Ln = Sm, y = 0.5, x = 1, z = 3 (3); Ln = Eu, y = 0.5, z = 3 (4); Ln = Tb, y = 0.5, x = 1, z = 1.5 (5); Ln = Lu, y = 0.5, x = 1, z = 1.5 (6)) (trigonal, P-3, Z = 2) show that the covalent tripod trenphen undergoes a rearrangement in the presence of lanthanide ions yielding three tridentate binding units which encapsulate the nine-coordinated lanthanide ion with a slightly distorted, tricapped, trigonal prismatic coordination geometry. The correlation observed between the decrease of Ln-N distances and the metal ionic radius indicates that trenphen, although containing rigid bidentate phenanthroline units, is sufficiently flexible to self-organize without steric constraints around lanthanide ions of different size. Solution-state NMR studies show that complexes 2-6 exist in acetonitrile solution as discrete rigid C3-symmetric species retaining the triple-helical structure observed in the solid state. NMR and ES-MS titration show the formation of bimetallic and trimetallic species in the presence of an excess of metal, whereas mononuclear bistrenphen complexes are obtained in the presence of an excess of ligand. PMID- 11196808 TI - Synthesis and Mossbauer spectroscopic studies of chemically oxidized ferrocenyl(phenyl)phosphines. AB - The electrochemical potentials of Fc3-xPPhx, (1-3, x = 0-2) and (FcPPh)n (4) indicate that iodine should oxidize ferrocenyl(phenyl)phosphines. The molar conductivity of solutions of 1-3 increases sharply when the solutions are titrated with iodine, leveling off after the addition of > 2 equiv of oxidant, consistent with formation of 1:1 electrolytes. Diamagnetic salts 6-9 are observed upon addition of a benzene solution of iodine to a benzene solution of 1-4 at ambient temperature in ratios of I2/metallocene ranging from 1:1 to 2:1. Well resolved 1H and 31P NMR spectra are obtained for 6-8. Absorptions assigned to the I3- anion dominate the UV-vis spectrum of 6-8, whereas characteristic absorptions for [Fc][I3] are absent. Mossbauer spectra of 7-9 reveal isomer shifts consistent with low-spin iron(II) in ferrocene derivatives rather than those in ferricenium ions. Small amounts of low-spin FeIII appear to be present in 6. Taken together, the results suggest that 6-9 are iodophosphonium salts and not ferricenium salts. Diferrocenyl(phenyl)phosphine oxide (5) reacts with iodine to produce a diamagnetic, dark solid 10. Low-spin FeII is observed at 77 and 293 K in the Mossbauer spectra of 10 with no evidence for oxidation of FeII to FeIII. Compound 10 is proposed to be a neutral complex between 5 and I2. Reactions between 5 and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) yield [Fc2P(=O)][DDQ]2 (11). Mossbauer spectroscopy of 11 indicates the presence of a mixture of low-spin FeII and low-spin FeIII at 77 K, suggesting that some electron transfer occurs from 5 to DDQ. The fraction of low-spin FeIII increases at room temperature. PMID- 11196809 TI - Pentadentate terpyridine-catechol linked ligands and their cobalt(III) complexes. AB - A series of novel pentadentate terpyridine-catechol linked ligands were prepared, in which the terpyridine and catechol moieties were linked together by (CH2)n chains of different lengths (n = 4-6). Together with 1-methylimidazole, these ligands formed low-spin, six-coordinate Co(III) complexes. Two of the complexes (n = 4, 5) were characterized by X-ray crystallography [n = 4, monoclinic, P2(1)/c, a = 14.957(7) A, b = 10.585(9) A, c = 23.033(7) A, beta = 106.01(3) degrees, V = 3505(3) A3, Z = 4, R = 0.063; n = 5, monoclinic, P2(1)/c, a = 8.848(7) A, b = 15.78(1) A, c = 25.455(7) A, beta = 93.90(5) degrees, V = 3544(3) A3, Z = 4, R = 0.056], which revealed similar structures around the Co(III) centers but different conformations for the (CH2)n linkers. The (CH2)4 linker showed a straight, symmetric conformation whereas the (CH2)5 linker showed a curved conformation that allowed the accommodation of one extra CH2 unit, suggesting that the (CH2)4 linker presents the "best-fit" length for these complexes. PMID- 11196810 TI - Effects of substituents on the thermodynamic and kinetic stabilities of HCGeX (X = H, CH3, F, and Cl) isomers. A theoretical study. AB - The effect of substitution on the potential energy surfaces of HC identical to GeX (X = H, CH3, F, and Cl) were explored using density functional theory (B3LYP) and QCISD methods. The theoretical findings suggest that (H)(X)C = Ge: is the minimum on the singlet potential energy surface, regardless of the substituents (X) used. On the other hand, HC identical to GeX and XC identical to GeH are found to be local minima on the surface, but they are neither kinetically nor thermodynamically stable. PMID- 11196812 TI - Syntheses and electronic spectroscopy of [PtL(L')][ClO4] complexes (HL = 6-phenyl 2,2'-bipyridine; L' = pyridine, 4-aminopyridine, 2-aminopyridine, and 2,6 diaminopyridine). AB - Four cyclometalated Pt(II) complexes, [PtL(L')][ClO4] [HL = 6-phenyl-2,2' bipyridine; L' = pyridine (1), 4-aminopyridine (2), 2-aminopyridine (3), 2,6 diaminopyridine (4)], were designed and synthesized to probe intramolecular N...Pt interactions. The crystal structures of the compounds show that the pyridine ligands are almost perpendicular to the planes of the molecules. In addition, the pendant NH2 groups of the 2-aminopyridine and 2,6-diaminopyridine ligands are close to the metal centers in complexes 3 and 4, with the Pt-N(H2) distances (3.065(3)-3.107(3) A) significantly shorter than the sum of the van der Waals radii of Pt and N. These compounds were also studied by electronic spectroscopy. All the complexes display intense intraligand pi-->pi* transitions at 200-340 nm (epsilon = 10(4)-10(3) M-1 cm-1) and moderately intense (epsilon approximately 10(3) M-1 cm-1) metal (Pt)-to-ligand (pi*) charge-transfer (MLCT) transitions. For 1 and 2, the MLCT transitions occur at approximately 390 nm, but the MLCT transition of 4 is exceptionally low in energy (492 nm). The low temperature emission spectra of the complexes in frozen EMD glass indicate that 3 pi pi* is the emissive excited state for 1 and 2 but the emission of 3 is from a 3MLCT excited state. On the basis of the spectroscopic results, the order of energy of the MLCT excited states is established as 1 approximately 2 > 3 > 4. It is proposed that the red shifts of the MLCT transitions in 3 and 4 are due to increased electron-donating abilities of the ancillary pyridine ligands and intramolecular interactions between the orbitals of amine nitrogen lone pairs. Crystal data for the complexes are as follows. 1: triclinic P1, Z = 2, a = 8.7917(2) A, b = 10.6398(3) A, c = 11.9592(3) A, alpha = 107.130(1) degrees, beta = 92.522(1) degrees, gamma = 111.509(1) degrees. 2.CH3CN: triclinic P1, Z = 2, a = 7.0122(4) A, b = 12.9653(8) A, c = 14.0283(9) A, alpha = 107.3100(10) degrees, beta = 102.7640(10) degrees, gamma = 91.6320(10) degrees. 3.CH3CN: triclinic P1, Z = 2, a = 7.6459(1) A, b = 10.8433(1) A, c = 14.8722(2) A, alpha = 99.383(1) degrees, beta = 93.494(1) degrees, gamma = 101.385(1) degrees. 4.CH3CN: triclinic P1, Z = 2, a = 7.862(2) A, b = 10.977(3) A, c = 14.816(5) A, alpha = 99.34(2) degrees, beta = 92.64(2) degrees, gamma = 104.11(2) degrees. PMID- 11196811 TI - pH-controlled change of the metal coordination in a dicopper(II) complex of the ligand H-BPMP: crystal structures, magnetic properties, and catecholase activity. AB - The dinucleating ligand 2,6-bis[(bis(2-pyridylmethyl)amino)methyl]-4-methylphenol (H-BPMP) has been used to synthesize the three dinuclear Cu(II) complexes [Cu2(BPMP)(OH)][ClO4](2).0.5C4H8O (1), [Cu2(BPMP)(H2O)2](ClO4)(3).4H2O (2), and [Cu2(H-BPMP)][(ClO4)4].2CH3CN (3). X-ray diffraction studies reveal that 1 is a mu-hydroxo, mu-phenoxo complex, 2 a diaqua, mu-phenoxo complex, and 3 a binuclear complex with Cu-Cu distances of 2.96, 4.32, and 6.92 A, respectively. Magnetization measurements reveal that 1 is moderately antiferromagnetically coupled while 2 and 3 are essentially uncoupled. The electronic spectra in acetonitrile or in water solutions give results in accordance with the solid state structures. 1 is EPR-silent, in agreement with the antiferromagnetic coupling between the two copper atoms. The X-band spectrum of powdered 2 is consistent with a tetragonally elongated square pyramid geometry around the Cu(II) ions, in accordance with the solid-state structure, while the spectrum in frozen solution suggests a change in the coordination geometry. The EPR spectra of 3 corroborate the solid-state and UV-visible studies. The 1H NMR spectra also lead to observations in accordance with the conclusions from other spectroscopies. The electrochemical behavior of 1 and 2 in acetonitrile or in water solutions shows that the first reduction (Cu(II)Cu(II)-Cu(II)Cu(I) redox couple) is reversible and the second (formation of Cu(I)Cu(I) irreversible. In water, 1 and 2 are reversibly interconverted upon acid/base titration (pK 4.95). In basic medium a new species, 4, is reversibly formed (pK 12.0), identified as the bishydroxo complex. Only 1 exhibits catecholase activity (oxidation of 3,5-di tert-butylcatechol to the corresponding quinone, vmax = 1.1 x 10(-6) M-1 s-1 and KM = 1.49 mM). The results indicate that the pH dependence of the catalytic abilities of the complexes is related to changes in the coordination sphere of the metal centers. PMID- 11196813 TI - Dimolybdenum bis((S,S,S)-triisopropanolaminate(3-)): a blue compound with an unusual Mo-Mo triple bond. AB - Mo2(OtBu)6 and Mo2(NMe2)6 each react with (S,S,S)-triisopropanolamine (2 equiv) in benzene to yield dimolybdenum bis((S,S,S)-isopropanolaminate(3-)), Mo2[(OC-(S) HMeCH2)3N]2 (M identical to M), as a blue crystalline solid. Cell parameters at 160 degrees C: a = 17.389(6) A, b = 10.843(3) A, c = 10.463(3) A, beta = 125.28(1) degrees, Z = 2 in space group C2. The molecular structure involves an Mo2 unit inside an O6N2 distorted cubic box. The Mo2 axis is disordered about three positions with occupancy factors of ca. 45%, 45%, and 10%. Despite this disorder, the molecular structure is shown to contain a central Mo identical to Mo unit of distance 2.15(3) A coordinated to two triolate ligands which each have two chelating arms and one that spans the Mo identical to Mo bond. The local Mo2O6N2 moiety has approximate C2h symmetry, and the Mo-N distances are long, 2.4 A. The 1H and 13C(1H) NMR spectra recorded in benzene-d6 are consistent with the geometry found in the solid-state structure. The blue color arises from weak absorptions, epsilon approximately 150 dm3 mol-1 cm-1, at 580 and 450 nm in the visible region of the electronic absorption spectrum. Raman spectra recorded in KCl reveal pronounced resonance effects with excitation wavelengths of 488.0, 514.5, and 568.2 nm, particularly for the 322 cm-1 band, which can probably be assigned to nu(Mo identical to Mo). The electronic structure of this compound is investigated by B3LYP DFT calculations, and a comparison is made with the more typical ethane-like (D3d) Mo2(OR)6 compounds is presented. The distortion imposed on the molecule by the triisopropanolaminate(3-) ligands removes the degeneracy of the M-M pi molecular orbitals. The HOMO and SHOMO are both M-M pi and M-O sigma* in character, while the LUMO is M-M pi* and the SLUMO is predominantly M-O sigma* with metal sp character. The calculated singlet-singlet transition energies are compared with those implicit in the observed electronic spectrum. PMID- 11196814 TI - Surface-enhanced Raman scattering and surface-enhanced resonance Raman scattering excitation profiles of Ag-2,2'-bipyridine surface complexes and of [Ru(bpy)3]2+ on Ag colloidal surfaces: manifestations of the charge-transfer resonance contributions to the overall surface enhancement of Raman scattering. AB - Excitation profiles of SERS (surface-enhanced Raman scattering) and/or SERRS (surface-enhanced resonance Raman scattering) spectral bands of two forms of a Ag bpy (bpy = 2,2'-bipyridine) surface complex and of [Ru(bpy)3]2+ on Ag nanoparticle (hydrosol) surfaces were determined from the spectra excited in the 458-600 nm region and are reported together with the FT-SERS spectra of the Ag bpy surface complex and FT Raman spectra of [Ru(bpy)3] Cl2. Seven of the observed 11 fundamentals as well as their first overtones and combination bands are selectively enhanced in SERS of the Ag-bpy surface complex formed in the Ag colloid/HCl/bpy system. The profiles of these bands show a common maximum at approximately 540 nm. The selectively enhanced bands of the Ag-bpy surface complex have nearly the same wavenumbers as those enhanced in the SERRS and resonance Raman spectra of [Ru(bpy)3]2+ upon excitation close to the 453 nm maximum of its MLCT absorption band. Moreover, the intensity patterns of the bpy vibrations of the two species match both in resonance (541 nm excitation for Ag bpy, 458 nm for [Ru(bpy)3]2+) and in off-resonance (458 and 1064 nm for Ag-bpy, 1064 nm for [Ru(bpy)3]2+). The distinct band shapes of the excitation profiles of the selectively enhanced vibrational modes of the Ag-bpy surface complex, as well as the observation of overtones and combination bands in the SERS spectra upon excitation into this "band", are interpreted in terms of a charge-transfer resonance contribution to the overall SERS enhancement. In view of the near coincidence of the vibrational modes coupled to the resonant electronic transition of Ag-bpy with those coupled to the MLCT transition of [Ru(bpy)3]2+, the resonant electronic transition is tentatively assigned to a Ag metal to bpy (pi*) CT transition. PMID- 11196815 TI - Synthesis and structural characterization of luminescent trinuclear gold(I) complexes with dithiocarbamates. AB - We have synthesized a series of trinuclear gold(I) complexes, namely, [Au3(mu dpmp)(S2CNR2)nCl3-n] (n = 0-3; R = Me, CH2Ph), [Au3(mu-dpmp)(mu S2CNR2)Cl](CF3SO3) (R = Me, CH2Ph), and [Au3(mu-dpmp)(mu-S2CNMe2)(C6F5)]X (X = Cl, CF3SO3), containing the triphosphine dpmp [bis(diphenylphosphinomethyl)phenylphosphine] and varying amounts of dithiocarbamate. NMR experiments show fluxional behavior in solution for most of these derivatives because several arrangements of the ligands are possible. The crystal structure of [(mu-dpmp)(AuCl)3] has been determined by X-ray diffraction studies; the molecule displays mirror symmetry and involves an angular arrangement of the gold atoms [Au-Au-Au 119.603(14) degrees, Au-Au 3.3709(4) A]. We have studied the optical properties of these derivatives in the solid state, finding a red shift as a function of the dithiocarbamate number and, for some derivatives, wavelength-dependent emission spectra at low temperature. PMID- 11196816 TI - Electrophilic substitution of (diamine)tetrahydroxoplatinum(IV) with carboxylic anhydrides. Synthesis and characterization of (diamine)platinum(IV) complexes of mixed carboxylates. AB - A novel series of (diamine)platinum(IV) complexes of mixed carboxylates have been synthesized by electrophilic substitution of the tetrahydroxoplatinum(IV) complex (dach)Pt(OH)4 (dach = trans-(+/-)-1,2-diaminocyclohexane) with three different carboxylic anhydrides, pivalic, acetic, and trifluoroacetic anhydrides. Consecutive two-step acylations with two different carboxylic anhydrides in acetone or dichloromethane gave the mixed carboxylate complexes (dach)Pt(O2CR)x(O2CR')4 - x (R = C(CH3)3 or CF3, R' = CH3, x = 1-4) including all the possible stereoisomers, which could be separated and identified by means of HPLC, column chromatography, 1H NMR, and X-ray crystallography. From analysis of the reaction products we have found that the positions of electrophilic substitution of (dach)Pt(OH)4 were influenced by the kinds of carboxylic anhydrides exhibiting different electrophilicity or steric effects. The initial substitution by the first reactant occurs more favorably on axial OH, but in the case of pivalic anhydride, equatorial substitution is favored probably because of the bulkiness of the pivalate group. Such a result seems to be related to their stereochemical factors rather than to differences in electrophilicity. The lipophilicity of the title complexes was affected not only by the carbon numbers of substituents but also by the conformation of the resulting compound. PMID- 11196817 TI - Syntheses and structures of rhenium(IV) and rhenium(V) complexes with ethanedithiolato ligands. AB - A novel dimeric rhenium(IV) complex, [Re2(SCH2CH2S)4], and a monomeric methyloxorhenium(V) complex, [CH3ReO(SCH2CH2S)PPh3], were synthesized from methyloxorhenium(V) complexes and characterized crystallographically. The structure of [Re2(SCH2CH2S)4], the formation reaction of which showed surprising demethylation conceivably through the homolytic cleaveage of the rhenium-carbon bond, features distorted trigonal prismatic coordination of sulfurs around the metal center and a rhenium-rhenium triple bond. A revised structure, [Tc2(SCH2CH2S)4], is proposed for a related technetium complex, originally identified as [Tc2(SCH2CH2S)2(SCH=CHS)2] (Tisato et al. Inorg. Chem. 1993, 32, 2042). Additionally, a new compound, CH3Re(O)(SPh)2PPh3, was prepared. PMID- 11196818 TI - Detection of the EPR spectra of NO. in ruthenium(II) complexes. AB - The EPR of NO. can be detected in the liquid and solid states when crystal fields are sufficient to remove the axial symmetry and separate the (pi*)x and (pi*)y orbitals by a few hundred reciprocal centimeters. The theory of the EPR spin Hamiltonian of bound NO. is reviewed, further developed, and then applied to the observed frozen-liquid spectra of NO. bound to Ru(II) obtained from RuIINO+ complexes by reduction. Comparisons to earlier reports on the observation of the EPR spectra of NO. are made. PMID- 11196819 TI - Synthesis and structural characterization of highly chlorinated, brominated, iodinated, and methylated carborane anions, 1-H-CB9X9-, 1-NH2-CB9X9- (X = Cl, Br, I), and 1-H-CB9(CH3)9-. AB - The highly chlorinated, brominated, and iodinated carborane anions 1-R-CB9X9- (R = H, NH2; X = Cl, Br, I) were prepared in high yields by treatment of [Me3NH][1-R CB9H9] with excess ICl, Br2/triflic acid, and I2/triflic acid, respectively, in sealed tubes at 180-240 degrees C. With the aid of a Pd catalyst, B-I bonds could be converted into the B-Me bonds by treatment with excess MeMgBr, which led to the preparation of the permethylated species 1-H-CB9Me9- in good yield. These new anions were fully characterized by 1H, 13C, and 11B NMR, IR, and negative-ion MALDI MS spectroscopy. Some were further characterized by single-crystal X-ray analyses. The weakly coordinating nature of these new anions was probed by 29Si chemical shifts. PMID- 11196820 TI - Mono- and dinuclear ruthenium(II) and osmium(II) polypyridine complexes built around spiro-bridged bis(phenanthroline) ligands: synthesis, electrochemistry, and photophysics. AB - Two new dyads have been synthesized in which terminal Ru(II) and Os(II) polypyridine complexes are separated by sterically constrained spiro bridges. The photophysical properties of the corresponding mononuclear complexes indicate the importance of the decay of the lowest-energy triplet states localized on the metallo fragments through the higher-energy metal-centered excited states. This effect is minimized at 77 K, where triplet lifetimes are relatively long, and for the Os(II)-based systems relative to their Ru(II)-based counterparts. Intramolecular triplet energy transfer takes place from the Ru(II)-based fragment to the appended Os(II)-based unit, the rate constant being dependent on the molecular structure and on temperature. In all cases, the experimental rate constant matches surprisingly well with the rate constant calculated for Forster type dipole-dipole energy transfer. As such, the disparate rates shown by the two compounds can be attributed to stereochemical factors. It is further concluded that the spiro bridging unit does not favor through-bond electron exchange interactions, a situation confirmed by cyclic voltammetry. PMID- 11196821 TI - Analysis of the spin exchange interactions in the three phases of vanadium pyrophosphate, (VO)2P2O7, in terms of spin-orbital interaction energy. AB - The spin exchange interactions in the ambient-pressure orthorhombic (APO), high pressure orthorhombic (HPO), and ambient-pressure monoclinic (APM) phases of the vanadium pyrophosphate, (VO)2P2O7, were analyzed by calculating the spin-orbital interaction energies delta e-delta e0 of their spin dimers. The anisotropy of the spin exchange interactions in the HPO phase is well explained by the delta e delta e0 values. For the APO phase, the reported crystal structure does not provide accurate enough delta e-delta e0 values to conclude unambiguously which of the V1-V2 and V3-V4 chains has a larger spin gap and which of the bridged and edge-sharing spin dimers has a stronger spin exchange interaction in the V1-V2 and V3-V4 chains. The APM phase is predicted to exhibit essentially two spin gaps, with a large spin gap for the V8-V5-V7-V6 chain and a very small one for the V4-V2-V3-V1 chain. PMID- 11196822 TI - Stabilization of high-valent metals by corroles: oxo[tris(pentafluorophenyl)corrolato]chromium(V). AB - The aerobic reaction of Cr(CO)6 with tris(pentafluorophenyl)corrole (H3(TpFPC)) in toluene gives the dark red oxochromium(V) compound (TpFPC)Cr(O), which has been characterized by X-ray crystallography, electrochemistry, and EPR spectroscopy. Short Cr-N (1.927-1.943 A) bonds as well as relatively large 14N and small 53Cr coupling constants suggest that sigma (N-->Cr) donation is responsible for the unusual stability of chromium(V) in this complex. The CrV/IV reduction potential (0.11 V vs Ag/AgCl) is 0.65 V below that of oxo(tetramesitylporphinato)chromium(V). PMID- 11196823 TI - Countercomplementarity and strong ferromagnetic coupling in a linear mixed mu acetato, mu-hydroxo trinuclear copper(II) complex. Synthesis, structure, magnetic properties, EPR, and theoretical studies. AB - The structural and magnetic data of the trinuclear compound [Cu3(L)2(CH3COO)2(OH)2(dmf)2] (HL = N-(2-methylpyridyl)toluensulfonylamide) are reported. The compound crystallizes in the monoclinic system, space group P2(1)/n (no. 14), with a = 11.6482(6) A, b = 13.5772(6) A, c = 13.5306(7) A, alpha = 90 degrees, beta = 92.859(5) degrees, gamma = 90 degrees, and Z = 2. The three copper atoms form an exact linear arrangement. Neighboring coppers are connected by a hydroxo bridge and a bidentate syn-syn carboxylato group. The coordination spheres of the terminal copper atoms are square pyramidal with a dmf molecule as the apical ligand. The central copper has a regular square planar geometry. The mixed bridging by a hydroxide oxygen atom and a bidentate carboxylato group leads to a noncoplanarity of the adjacent basal coordination planes with a dihedral angle of 51.96(9) degrees. Susceptibility measurements (2-300 K) reveal a strong ferromagnetic coupling, J = 93(6) cm-1, in the mixed-bridged moiety leading to a quartet ground state that is confirmed by the EPR spectra. The ferromagnetic exchange coupling is discussed using DFT calculations on model compounds that have shown a countercomplementary effect of the hydroxo and acetate bridges. PMID- 11196824 TI - Single-molecule magnets: a new class of tetranuclear manganese magnets. AB - The preparation, X-ray structure, and detailed physical characterization are presented for a new type of single-molecule magnet [Mn4(O2CMe)2(pdmH)6](ClO4)2 (1). Complex 1.2MeCN.Et2O crystallizes in the triclinic space group P1, with cell dimensions at 130 K of a = 11.914(3) A, b = 15.347(4) A, c = 9.660(3) A, alpha = 104.58(1) degree, beta = 93.42(1) degree, gamma = 106.06(1) degree, and Z = 1. The cation lies on an inversion center and consists of a planar Mn4 rhombus that is mixed-valent, MnIII2MnII2. The pdmH- ligands (pdmH2 is pyridine-2,6 dimethanol) function as either bidentate or tridentate ligands. The bridging between Mn atoms is established by either a deprotonated oxygen atom of a pdmH- ligand or an acetate ligand. The solvated complex readily loses all acetonitrile and ether solvate molecules to give complex 1, which with time becomes hydrated to give 1.2.5H2O. Direct current and alternating current magnetic susceptibility data are given for 1 and 1.2.5H2O and indicate that the desolvated complex has a S = 8 ground state, whereas the hydrated 1.2.5H2O has a S = 9 ground state. Ferromagnetic interactions between MnIII-MnII and MnIII-MnIII pairs result in parallel spin alignments of the S = 5/2 MnII and S = 2 MnIII ions. High-frequency EPR spectra were run for complex 1.2.5H2O at frequencies of 218, 328, and 436 GHz in the 4.5-30 K range. A magnetic-field-oriented polycrystallite sample was employed. Fine structure is clearly seen in this parallel-field EPR spectrum. The transition fields were least-squares-fit to give g = 1.99, D = -0.451 K, and B4 degrees = 2.94 x 10(-5) K for the S = 9 ground state of 1.2.5H2O. A molecule with a large-spin ground state with D < 0 can function as a single-molecule magnet, as detected by techniques such as ac magnetic susceptibility. Out-of-phase ac signals (chi'' M) were seen for complexes 1 and 1.2.5H2O to show that these complexes are single-molecule magnets. A sample of 1 was studied by ac susceptibility in the 0.4-6.4 K range with the ac field oscillating at frequencies in the 1.1-1000 Hz range. A single peak in chi'' M vs temperature plots was seen for each frequency; the temperature of the chi'' M peak varies from 2.03 K at 995 Hz to 1.16 K at 1.1 Hz. Magnetization relaxation rates were evaluated in this way. An Arrhenius plot gave an activation energy of 17.3 K, which, as expected, is less than the 22.4 K value calculated for the thermodynamic barrier for magnetization direction reversal for an S = 8 complex with D = -0.35 K. The 1.2.5H2O complex with an S = 9 ground state has its chi'' M peaks at higher temperatures. PMID- 11196825 TI - Catecholate/salicylate heteropodands: demonstration of a catecholate to salicylate coordination change. AB - While iron release from enterobactin-mediated iron transport occurs primarily via an esterase that destroys the siderophore, other catechol siderophores that are not susceptible to hydrolysis act as bacterial growth factors. Elucidating the structures of protonated ferric enterobactin may reveal the pathway by which synthetic analogues fulfill bacterial iron requirements. In order to more completely model this potential delivery pathway for ferric iron, as well as to understand the pH dependent structural dynamics of ferric enterobactin, two ligands, (2-hydroxybenzoyl-2-aminoethyl)-bis(2,3-dihydroxybenzoyl-2 aminoethyl)amine (TRENCAMSAM) and (2-hydroxy-3-methoxybenzoyl-2-aminoethyl) bis(2,3-dihydroxybenzoyl-2- aminoethyl)amine (TRENCAM(3M)SAM), have been synthesized as models for monoprotonated enterobactin. The coordination chemistry of these ligands with Fe3+ and Al3+ has been investigated. Fe[TRENCAMSAM]2- crystallizes in the triclinic space group P1: Z = 1, a = 11.3307(6) A, b = 12.5479(7) A, c = 15.5153(8) A, alpha = 94.513(1) degree, beta = 105.867(1) degree, gamma = 94.332(1) degree. The structure is a two-metal two-ligand dimer supported by mu-oxo bridges from two catecholate moieties. Al[TRENCAMSAM]2- crystallizes in the triclinic space group P1: Z = 2, a = 9.1404(2) A, b = 13.3570(1) A, c = 15.5950(1) A, alpha = 95.711(1) degree, beta = 104.760(1) degree, gamma = 92.603(1) degree. The complex is a monomer with a five coordinate, square-pyramidal aluminum cation. Al[TRENCAM(3M)SAM]2- crystallizes in the monoclinic space group C2/m: Z = 8, a = 34.244(2) A, b = 11.6206(6) A, c = 21.9890(12) A, beta = 101.478(1) degree. The complex is also a monomer, but with a highly distorted five-coordinate, square-pyramidal aluminum cation coordination sphere. At high pH these complexes do not display a salicylate mode of binding; however, at low pH Al[TRENCAMSAM]2- converts to protonated Al[H3TRENCAMSAM]+, which is a six-coordinate, tris-salicylate complex. Al[H3TRENCAMSAM]+ crystallizes in the triclinic space group P1: Z = 2, a = 11.5475(4) A, b = 12.1681(4) A, c = 12.5094(4) A, alpha = 109.142(1) degree, beta = 104.327(1) degree, gamma = 103.636(1) degree. This is the first catecholamide enterobactin analogue that has been structurally characterized in both a catecholate and salicylate mode of coordination. PMID- 11196826 TI - Band deconvolution analysis of the absorption and magnetic circular dichroism spectral data of a planar phthalocyanine dimer. AB - The electronic absorption and magnetic circular dichroism spectral data of a phthalocyanine dicopper complex that is deduced to be very planar and to share a common benzene ring have been studied by band deconvolution analysis. The results were compared with those of the molecular orbital (MO) calculations within the framework of the Pariser-Parr-Pople (PPP) approximation. The results of the band deconvolution analysis are in good agreement with those of the PPP calculations, allowing many bands to be reasonably assigned on the basis of the MO calculations. The validity of the PPP method for the MO calculation of large molecules is also emphasized. PMID- 11196828 TI - Mesogenic palladium complexes with pincer ligands derived from dipicolinic acid. AB - 4-Substituted pyridine-2,6-dicarboxylic acids, (E)-dipicH2, and 4-substituted pyridine-2,6-bis(thiocarboxylic) acids, (E)-pdtcH2, (E = OCnH2n + 1, SCnH2n + 1) have been synthesized and used as O,N,O- and S,N,S-pincer ligands with palladium. In the fourth coordination site the complexes bear 4-decyloxy-4'-stilbazole (L1), 4-decyloxy-N-(4-pyridylmethylene)anilines (L2), decyl 4-pyridinecarboxylate (L3), 4-(4'-decyloxyphenyl)pyridinecarboxylate (L4), 4-(3',4',5' tridecyloxybenzyl)pyridinecarboxylate (L5), 4-isocyano-1-decyloxybenzene (L6), or 4-isocyano-4'-decyloxybiphenyl (L7). Thermotropic mesomorphism is observed for the (E)-dipic complexes with L5 and n = 12, which display columnar phases. The complexes with S,N,S-pincers show an important depression in the melting point compared to their O,N,O homologues and this change gives rise to mesomorphic materials (SC). However, in the case of L5 the mesomorphic behavior observed for the O,N,O derivative is lost in its S,N,S analogue. The alkylsulfanyl compounds exhibit lower transition temperatures and wider mesophase ranges than their alkoxy analogues. PMID- 11196827 TI - Structural and photophysical studies of Cu(NN)2+ systems in the solid state. Emission at last from complexes with simple 1,10-phenanthroline ligands. AB - For a variety of reasons, relating the photophysical properties of a copper phenanthroline to a structure in solution is problematic. To elucidate some of the issues involved, in this paper we describe the crystal and molecular structures of a series of Cu(NN)2(+)-containing systems along with spectral data obtained from the solids themselves. The NN ligands investigated are tmp (3,4,7,8 tetramethyl-1,10-phenanthroline), dpdmp (2,9-diphenyl-4,7-dimethyl-1,10 phenanthroline), dptmp (2,9-diphenyl-3,4,7,8-tetramethyl-1,10-phenanthroline), and dipp (2,9-diisopropyl-1,10-phenanthroline). The results show that a flattening distortion can have a large impact on the spectroscopic properties of a Cu(NN)2+ system, whereas a typical rocking distortion has comparatively little effect. The reflectance spectra of orange or orange-red salts that have approximately perpendicular phenanthroline ligands exhibit absorption bands in the neighborhood of 460 nm along with a shoulder at longer wavelength. In the other limit, when a pronounced flattening distortion occurs and the dihedral angle between ligands is 20 degrees or more off perpendicular, the reflectance spectrum exhibits two distinct visible bands with intense absorption occurring at 525 nm or even longer wavelength. If the phenanthroline ligand lacks bulky substituents in the 2,9 positions, the compound may even be purple, depending on the counterion. Cu(NN)2+ complexes that contain phenyl substituents in the 2,9 positions and exhibit long-wavelength absorption in solution probably adopt a flattened structure in the ground electronic state. In most other systems ground state flattening is a solid-state effect induced by lattice forces. However, a flattening distortion is an intrinsic attribute of the emissive excited state, although intra- or intermolecular forces can inhibit the effect. In the case of the Cu(dptmp)2+ system, intramolecular steric interactions oppose flattening because the methyl groups in the 3,8 positions control the torsion angles of the neighboring phenyl groups. In the case of [Cu(tmp)2]BPh4, packing interactions induce a small flattening in the crystal, but they also constrain the degree of distortion that can occur in the excited state. As a consequence [Cu(tmp)2]BPh4 exhibits a weak photoluminescence in the solid phase (tau = 15 ns). This is the first report of emission from a bis(phenanthroline)copper(I) system that does not have bulky substituents in the 2 and/or 9 positions of the ligand. The [Cu(tmp)2]BPh4 system crystallizes in space group P2(1)/n with a = 17.4883(4) A, b = 9.86860(10) A, c = 26.3747(6) A, alpha = 90 degrees, beta = 97.7021(8) degrees, gamma = 90 degrees, V = 4510.8(3) A3, and Z = 4. For 12,948 unique data with Fo2 > 2 sigma(Fo2), R = 6.5%. The [Cu(dpdmp)2]PF6 system crystallizes in space group P2/n with a = 16.0722(13) A, b = 8.1100(7) A, c = 16.8937(10) A, alpha = 90 degrees, beta = 93.947(5) degrees, gamma = 90 degrees, V = 2196.8(5) A3, and Z = 2. For 2833 unique data with Fo2 > 2 sigma(Fo2), R = 6.0%. The [Cu(dptmp)2]PF6.THF system crystallizes in space group P1 with a = 12.8486(4) A, b = 13.7341(1) A, c = 15.1678(3) A, alpha = 99.5819(14) degrees, beta = 96.7263(13) degrees, gamma = 97.3311(12) degrees, V = 2591.3(2) A3, and Z = 2. For 13,753 unique data with Fo2 > 2 sigma(Fo2), R = 7.4%. Finally, the [Cu(dipp)2]TFPB system crystallizes in space group P1 with a = 14.2523(3) A, b = 16.0496(4) A, c = 17.5801(3) A, alpha = 112.4150(13) degrees, beta = 105.7480(13) degrees, gamma = 99.6078(11) degrees, V = 3408.7(3) A3, and Z = 2. For 8774 unique data with Fo2 > 2 sigma(Fo2), R = 9.3%. PMID- 11196829 TI - N-porphyrinylamino and -amido compounds by addition of an amino or amido nitrogen to a porphyrin meso position. AB - This report describes the synthesis and characterization of a series of octaethylporphyrin derivatives in which the porphyrin pi-network is connected to phenyl, 3-fluoranthenyl, or 1-pyrenyl aromatic systems through a meso amino or amido nitrogen. Metal-free bases and zinc(II) and iron(III) complexes have been obtained. These compounds represent the first examples of linkages between porphyrins and extended pi-networks through a nitrogen atom directly attached to a porphyrin meso position. 1H NMR studies of the metal-free bases and zinc complexes showed that in the amido-linked adducts, the plane containing the aryl substituent was oriented perpendicular to the plane of the porphyrin. Linkage through the secondary amino nitrogen, however, allowed the aryl plane to rotate toward coplanarity with the porphyrin plane, resulting in conjugation of the highest occupied aryl and porphyrin molecular orbitals through the nitrogen lone pair. In developing routes to the amino-linked compounds, the facile formation of fused azaaryl chlorins via an oxidative intramolecular cycloaddition was observed. An aryl carbon ortho to the meso linkage attacked the beta-carbon of an adjacent pyrrole ring, accompanied by 1,2-migration of a pyrrole beta-ethyl substituent and a two-electron oxidation of the initially formed macrocycle. The resulting structures are analogous to benzochlorins. The electronic spectra of the metal-free bases are characterized by intense, long-wavelength bands in the visible region. Molecular structures of the chloroferric complexes of the azabenzofluorantheno- and azabenzpyrenoporphyrin macrocycles (derived from fusion of the fluoranthenyl and pyrenyl substituents, respectively) were obtained by X ray diffraction. The porphyrin moiety in the azabenzofluoranthenoporphyrin adopted a gable structure, with a 22 degrees fold along a diagonal including the pyrrole-ring C4 and C16 alpha-carbons. By contrast, the azabenzpyrenoporphyrin was virtually planar. PMID- 11196830 TI - Definitive assignment of the g tensor of [Fe(OEP)(NO)] by single-crystal EPR. AB - Single-crystal EPR measurements have been performed on the triclinic form of [Fe(OEP)(NO)] (Ellison, M. K.; Scheidt, W. R. J. Am. Chem. Soc. 1997, 119, 7404) and on the isomorphous cobalt derivative [Co(OEP)(NO)] (Ellison, M. K.; Scheidt, W. R. Inorg. Chem. 1998, 37, 382) which has been doped with [Fe(OEP)(NO)]. Principal values of the g tensor determined at room temperature are gmax = 2.106, gmid = 2.057, and gmin = 2.015. The principal direction associated with the minimum g value lies 8 degrees from the Fe-N(NO) direction, 2 degrees from the normal to the heme plane, and 42 degrees from the N-O direction. The direction associated with the maximum g value lies 9 degrees from the normal to the Fe-N-O plane. The fact that the direction of gmin is near the Fe-N(NO) direction is consistent with the dominant role of spin-orbit coupling at the iron atom in determining the g tensor and with the picture of the electronic structure of the compound from restricted calculations, which makes the half-filled orbital mostly dz2 on the iron atom. The hyperfine tensor is nearly isotropic and was only resolved in the doped samples. Principal values of the A tensor determined at room temperature are 40.9, 49.7, and 42.7 MHz. Principal values of the g tensor determined from the doped samples at 77 K are gmax = 2.110, gmid = 2.040, and gmin = 2.012. Principal values of the A tensor are 42.5, 52.8, and 44.1 MHz at 77 K. The small change in g values with temperature is in contrast to the large temperature dependence on g values observed in samples of MbNO (Hori et al. J. Biol. Chem. 1981, 256, 7849). PMID- 11196831 TI - meso-Aryl smaragdyrins: novel anion and metal receptors. AB - An easy synthesis of core-modified meso-aryl smaragdyrins containing oxygen and sulfur in addition to pyrrole nitrogens has been achieved through an alpha-alpha coupling involving modified tripyrrane and dipyrromethane. The complexation behavior of these macrocycles toward anions (Cl-, F-, AMP-) and metal cations (Rh(I), Ni(II)) is reported. Specifically, it has been shown that the Rh(I) and Ni(II) ions bind to the smaragdyrin skeleton in its free base form. X-ray structural studies of Rh(I) complex 1 indicate an eta 2-type coordination involving only one imino and one amino nitrogen of the dipyrromethane unit. However, all four bipyrrole nitrogens participate in the coordination with the Ni(II) ion. Furthermore, Ni(II) coordination oxidizes the ligand, and the complex is formulated as the pi-cation radical of nickel(II) smaragdyrin. The anion complexation is followed in both the solid and solution phases. Solution studies reveal that the binding constants of the ions with the protonated form of smaragdyrin vary as F- > AMP- > Cl-. The X-ray structure of the chloride anion complex reveals that the chloride ion is bound above the cavity of the smaragdyrin macrocycle through three N-H...Cl hydrogen bonds. Crystal data with Mo K alpha (lambda = 0.710,73 A) are as follows: 1, C41H27N4O3Rh, a = 11.836(8) A, b = 12.495(9) A, c = 12.670(2) A, alpha = 69.09(6) degrees, beta = 78.78(6) degrees, gamma = 77.02(5) degrees, V = 1692.1(17) A3, Z = 2, triclinic, space group P-1, R1 (all data) = 0.0471; 4.HCl, C41H29N4O1Cl, a = 11.878(2) A, b = 17.379(4) A, c = 16.015(3) A, beta = 109.546(10) degrees, V = 3115.47(11) A3, Z = 4, monoclinic, space group P2(1)/c, R1(all data) = 0.0850. PMID- 11196832 TI - Syntheses and structures of the arylaluminum chalcogenides (ArAlE)2 (Ar = 2 (NEt2CH2)-6-MeC6H3, E = Se; Ar = 2,6-(NEt2CH2)2C6H3, E = Se, Te). AB - Two intramolecular stabilized arylaluminum dihydrides, (2-(NEt2CH2)-6-MeC6H3)AlH2 (1) and (2,6-(NEt2CH2)2C6H3)AlH2 (2), were prepared by reducing the corresponding dichlorides with an excess of LiAlH4 in diethyl ether. Reactions of 1 and 2 with elemental selenium afforded the dimeric arylaluminum selenides [(2-(NEt2CH2)-6 MeC6H3)AlSe]2 (3) and [(2,6-(NEt2CH2)2C6H3)AlSe]2 (4). Reaction of 2 with metallic tellurium gave the dimeric arylaluminum telluride [(2,6 (NEt2CH2)2C6H3)AlTe]2 (5). The possible reaction pathway is discussed, and molecular structures determined by single-crystal X-ray analyses are presented for 3 and 5. PMID- 11196833 TI - Raman study of the hexafluoroaluminate ion in solid and molten FLINAK. AB - Raman spectra have been obtained for matrix-isolated AlF6(3-) in an LiF/NaF/KF (FLINAK) eutectic mixture. Three Raman bands characteristic of the hexafluoroaluminate ion were identified in the solids formed from FLINAK melts which contained small amounts (5-11 mol%) of either AlF3 or Na3AlF6. The three allowed Raman-active bands of the matrix-isolated octahedral complex ion, nu 1(A1g), nu 2(Eg), and nu 5(F2g), were observed at 560.5, 380, and 325 cm-1, respectively, for the solid sample at 25 degrees C. Wavenumbers and relative intensities were similar to those of Na3AlF6 (cryolite), K3AlF6, and K2NaAlF6 (elpasolite) and other crystals known to contain discrete, octahedral AlF6(3-) ions. Peak positions, half-widths, and relative intensities for the bands were measured for samples at temperatures different from room temperature through the melting transition and into the molten state. The transition from high temperature solid to molten salt at about 455 degrees C occurred gradually without perceptible change in the peak positions, half-widths, or relative intensities. For a sample in molten FLINAK at 455 degrees C, the nu 1(A1g), nu 2(Eg), and nu 5(F2g) modes of the AlF6(3-) ion were observed at 542, 365, and 324 cm-1, respectively. Raman depolarization experiments were consistent with these assignments, and the low value of the depolarization ratio of the nu 1(A1g) mode at 542 cm-1 indicated that the sample was molten above 455 degrees C. Differential thermal analysis also indicated that the FLINAK samples melted at about 455 degrees C. Raman measurements were performed for samples at temperatures from 25 to 600 degrees C in a silver dish, on a hot stage, in an argon-filled atmosphere, under a microscope. Additional Raman experiments were performed on samples at temperatures from 25 to 750 degrees C in a conventional graphite windowless cell, in an argon-filled quartz tube, in a standard furnace. Over the concentration range 4.8-11 mol% AlF3 (CR 23-8.0) in FLINAK, only bands due to the AlF6(3-) ion were detected. There was no evidence to support the presence of other aluminum complexes in these melts. PMID- 11196835 TI - Ortho-linked polyaryloxide ligands and their titanium complexes. AB - Ortho-linked polyphenols, quaterphenol L(OH)4, and moderately hindered terphenol PhL(OH)3 are developed as new multidentate polyaryloxide ligands for transition metal chemistry. The polyphenols are synthesized using ortho-metalation and metal catalyzed cross-coupling methodologies; the synthetic routes allow for facile electronic and steric modification of the basic ligand design. The Ti(IV) coordination chemistry of these ligands reveals a diverse collection of bridged structures: dimeric [Ti(mu-PhLO3)(OiPr)]2 (P2(1)/n, a = 12.2699(5) A, b = 11.7957(5) A, c = 21.238(1) A, beta = 94.551(1) degrees, Z = 2, T = 170(2) K), dimeric [Ti2(mu-PhLO3)2(mu-Cl)(Cl)(THF)] (P1, a = 11.212(1) A, b = 14.165(1) A, c = 22.447(2) A, alpha = 90.440(4) degrees, beta = 93.345(4) degrees, gamma = 111.164(4) degrees, Z = 2, T = 170(2) K), and trimeric [Ti3(mu,mu'-LO4)(mu OiPr)2(OiPr)6] P2(1)/n, a = 11.1022(5) A, b = 18.7015(9) A, c = 24.409(1) A, beta = 95.369(2) degrees, Z = 4, T = 170(2) K). The reaction of TiCl3(THF)3 with [PhLO3]3- results in oxidation of Ti(III) to Ti(IV) and formation of the oxo dimer [Ti(PhLO3)(THF)]2(mu-O) (P1, a = 10.8649(6) A, b = 12.1882(7) A, c = 14.3349(9) A, alpha = 65.602(3) degrees, beta = 84.390(3) degrees, gamma = 86.582(3) degrees, Z = 1, T = 200(2) K); the oxo group presumably originates from the THF solvent. The titanium centers in these environments are either 5- or 6 coordinate, with distorted square pyramidal/trigonal bipyramidal and distorted octahedral geometries, respectively; the polyphenoxide chelate ligands are capable of bridging multiple oxophilic titanium sites. PMID- 11196834 TI - Electronic and resonance Raman spectra of [Au2(CS3)2]2-. Spectroscopic properties of a "short" Au(I)-Au(I) bond. AB - The anion [Au2(CS3)2]2- has an unusually short Au-Au distance (2.80 A) for a binuclear Au(I) complex. We report detailed Raman studies of the nBu4N+ salt of this complex, including FT-Raman of the solid and UV/vis resonance Raman of dimethyl sulfoxide solutions. All five totally symmetric vibrations of the anion have been located and assigned. A band at delta nu = 125 cm-1 is assigned to nu (Au2). The visible-region electronic absorption bands (384 (epsilon 30,680) and 472 nm (epsilon 610 M-1 cm-1)) are attributable to CS3(2-) localized transitions, as confirmed by the dominance of nu sym(C-Sexo) (delta nu = 951 cm-1) in RR spectra measured in this region. An absorption band at 314 nm (22,250 M-1 cm-1) is assigned as the metal-metal 1(d sigma*-->p sigma) transition, largely because nu sym(C-Sexo) is not strongly enhanced in RR involving this band. Observation of the expected strong resonance enhancement of nu (Au2) was precluded as a result of masking by intense solvent Rayleigh scattering in the UV. PMID- 11196836 TI - Solvothermal construction of a coordination polymer around in situ generated pyroglutamic acid: preparation, crystal structure, and magnetic behavior of [Mn(C5H6NO3)2]infinity. PMID- 11196837 TI - Model complexes for the active form of galactose oxidase. Physicochemical properties of Cu(II)- and Zn(II)-phenoxyl radical complexes. PMID- 11196838 TI - Reactivity of organometallic molybdate toward lanthanide cations. Synthesis and structure of polynuclear lanthanide-molybdate complexes. PMID- 11196840 TI - Conjugation involving nitrogen lone-pair electrons: can it lead to stable multiply charged cations? PMID- 11196839 TI - Synthesis and molecular structure of (TTP)Ti(1,2-eta 2-PhC identical to C-C identical to CPh). PMID- 11196841 TI - Nitrosyl transfer from manganese to iron in tropocoronand complexes. PMID- 11196842 TI - Ethylene oxide and propylene sulfide complexes of silver(I): synthesis and characterization of [HB(3,5-(CF3)2Pz)3]Ag(OC2H4) and [HB(3,5 (CF3)2Pz)3]Ag(SC3H6). PMID- 11196843 TI - A dichromium(II,II) compound with a strong antiferromagnetic coupling but little or no Cr-Cr bonding. PMID- 11196844 TI - The propionate of heme binds N4O2 Schiff base antimalarial drug complexes. PMID- 11196845 TI - Influencing the size of giant rings by manipulating their curvatures: Na6[Mo120O366(H2O)48H12(Pr(H2O)5)6](approximately 200H2O) with open shell metal centers at the cluster surface. PMID- 11196846 TI - Supramolecular coordination chemistry in aqueous solution: lanthanide ion-induced triple helix formation. AB - The self-assembly of dinuclear triple helical lanthanide ion complexes (helicates), in aqueous solution, is investigated utilizing laser-induced, lanthanide luminescence spectroscopy. A series of dinuclear lanthanide (III) helicates (Ln(III)) based on 2,6-pyridinedicarboxylic acid (dipicolinic acid, dpa) coordinating units was synthesized by linking two dpa moieties using the organic diamines (1R,2R)-diaminocyclohexane (chxn-R,R) and 4,4' diaminodiphenylmethane (dpm). Luminescence excitation spectroscopy of the Eu3+ 7F0-->5D0 transition shows the apparent cooperative formation of neutral triple helical complexes in aqueous solution, with a [Eu2L3] stoichiometry. Eu3+ excitation peak wavelengths and excited-state lifetimes correspond to those of the [Eu(dpa)3]3- model complex. CD studies of the Nd(III) helicate Nd2(dpa-chxn R,R)3 reveal optical activity of the f-f transitions, indicating that the chiral linking group induces a stable chirality at the metal ion center. Molecular mechanics calculations using CHARMm suggest that the delta delta configuration at the Nd3+ ion centers is induced by the chxn-R,R linker. Stability constants were determined for both ligands with Eu3+, yielding identical results: log K = 31.6 +/- 0.2 (K in units of M-4). Metal-metal distances calculated from Eu3+-->Nd3+ energy-transfer experiments show that the complexes have metal-metal distances close to those calculated by molecular modeling. The fine structure in the Tb3+ emission bands is consistent with the approximate D3 symmetry as anticipated for helicates. PMID- 11196847 TI - Mechanistic studies of (porphinato)iron-catalyzed isobutane oxidation. Comparative studies of three classes of electron-deficient porphyrin catalysts. AB - We report herein a comprehensive study of (porphinato)iron [PFe]-catalyzed isobutane oxidation in which molecular oxygen is utilized as the sole oxidant; these catalytic reactions were carried out and monitored in both autoclave reactors and sapphire NMR tubes. In situ 19F and 13C NMR experiments, coupled with GC analyses and optical spectra obtained from the autoclave reactions have enabled the identification of the predominant porphyrinic species present during PFe-catalyzed oxidation of isobutane. Electron-deficient PFe catalysts based on 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin [(C6F5)4PH2], 2,3,7,8,12,13,17,18 octabromo-5,10,15,20-tetrakis(pentafluorophenyl) porphyrin [Br8(C6F5)4PH2], and 5,10,15,20-tetrakis(heptafluoropropyl) porphyrin [(C3F7)4PH2] macrocycles were examined. The nature and distribution of hydrocarbon oxidation products show that an autoxidation reaction pathway dominates the reaction kinetics, consistent with a radical chain process. For each catalytic system examined, PFeII species were shown not to be stable under moderate O2 pressure at 80 degrees C; in every case, the PFeII catalyst precursor was converted quantitatively to high-spin PFeIII complexes prior to the observation of any hydrocarbon oxidation products. Once catalytic isobutane oxidation is initiated, all reactions are marked by concomitant decomposition of the porphyrin-based catalyst. In situ 17O NMR spectroscopic studies confirm the incorporation of 17O from labeled water into the oxidation products, implicating the involvement of PFe-OH in the catalytic cycle. Importantly, Br8(C6F5)4PFe-based catalysts, which lack macrocycle C-H bonds, do not exhibit augmented stability with respect to analogous catalysts based on (C6F5)4PFe and (C3F7)4PFe species. The data presented are consistent with a hydrocarbon oxidation process in which PFe complexes play dual roles of radical chain initiator, and the species responsible for the catalytic decomposition of organic peroxides. This modified Haber-Weiss reaction scheme provides for the decomposition of tert-butyl hydroperoxide intermediates via reaction with PFe-OH complexes; the PFeIII species responsible for hydroperoxide decomposition are regenerated by reaction of PFeII with dioxygen under these experimental conditions. PMID- 11196848 TI - Molecular mechanics calculations of 10-vertex boron cage compounds. AB - The model proposed earlier for molecular mechanics calculations of 7- and 12 vertex boranes, carboranes, and metallocarboranes has been extended to the case of 10-vertex borane cage compounds. To use the MM3 program with the standard connectivity file, and to avoid program alterations, the 10-vertex cages of the molecules were presented as a superposition of four formally independent fragments. Interactions between the fragments were described with a Hill-like potential, with the parameters adjusted for valence interactions. Standard values for the bond lengths and bond angles in the 10-vertex boron cage have been found by statistical analysis of X-ray data on borane cage compounds stored in the Cambridge Structural Database. Several substituted neutral molecules and anions have been considered, and good agreement of the calculated and experimental data has been obtained. Using the approach developed, the unknown structure of the [mu B20H16O(CH2)4O(CH2)2CH(CH3)2]3- ion has been calculated. PMID- 11196849 TI - Encapsulating bis(beta-ketoiminato) polyethers. Volatile, fluorine-free barium precursors for metal-organic chemical vapor deposition. AB - The synthesis, characterization, and incorporation in volatile metal-organic chemical vapor deposition (MOCVD) precursors of a new class of linked beta ketoiminate-polyether-beta-ketoiminate ligands is presented. These ligands are designed to encapsulate alkaline-earth cations having low charges and large ionic radii. Barium complexes having the general formula Ba[(RCOCHC(R')N)2(R")] (R = tert-butyl or CF3; R' = tert-butyl, methyl, or CF3; R" = -(CH2CH2O)4CH2CH2- or (CH2CH2O)5CH2CH2)-) were prepared and characterized by 1H and 13C NMR spectroscopy, elemental analysis, and mass spectrometry. Single-crystal X-ray diffraction analysis of 2,2,5,25,28,28-hexamethyl-9,12,15,18,21-pentaoxa-4,25 diene-6,24- diimino-3,27-pentacosadionatobarium(II) reveals a monomeric, nine coordinate, tricapped trigonal prismatic coordination geometry. Single-crystal X ray structural analysis of 1,1,1,24,24,24-hexafluoro-4,21-ditrifluoromethyl 8,11,14,17- tetraoxa-3,21-diene-5,20-diimino-2,23 tetracosadionatobarium(II).2DMSO reveals a monomeric, ten-coordinate, distorted tetracapped trigonal prismatic coordination geometry. Volatility data are presented for these barium complexes, demonstrating viability as MOCVD precursors. In addition, it is demonstrated that thin epitaxial films of BaTiO3 can be grown on (001) MgO by low-pressure MOCVD techniques using one of these barium complexes and Ti(dipivaloylmethanate)2(isopropoxide)2 as precursors. PMID- 11196850 TI - Luminescent chains formed from neutral, triangular gold complexes sandwiching TlI and AgI. Structures of (Ag([Au(mu-C2,N3-bzim)]3)2)BF4.CH2Cl2, (Tl([Au(mu-C2,N3 bzim)]3)2)PF(6).0.5THF (bzim = 1-benzylimidazolate), and (Tl([Au(mu C(OEt)=NC6H4CH3)]3)2)PF6.THF, with MAu6 (M = Ag+, Tl+) cluster cores. AB - It has been found that several trinuclear complexes of AuI interact with silver and thallium salts to intercalate Ag+ and Tl+ cations, thereby forming chains. The resulting sandwich clusters center the cations between the planar trinuclear moieties producing structures in which six AuI atoms interact with each cation in a distorted trigonal prismatic coordination. The resultant (B3AB3B3AB3)infinity pattern of metal atoms also shows short (approximately 3.0 A) aurophilic interactions between BAB molecular centers. These compounds display a strong visible luminescence, under UV excitation, which is sensitive to temperature and the metal ion interacting with the gold. X-ray crystal structures are reported for Ag([Au(mu-C2,N3-bzim)]3)2BF4CH2Cl2 (P1, Z = 2, a = 14.4505(1) A; b = 15.098(2)A; c = 15.957(1)A; alpha = 106.189(3) degrees; beta = 103.551(5) degrees; gamma = 101.310(5) degrees); Tl([Au(mu-C2,N3-bzim)]3)2PF(6)05C4H8O (P1, Z = 2, a = 15.2093(1)A; b = 15.3931(4)A; c = 16.1599(4)A; alpha = 106.018(1) degrees; beta = 101.585(2) degrees; gamma = 102.068(2) degrees); and Tl([Au(mu C(OEt)=NC6H4CH3)]3)2PF6.C4H8O (P2(1)/n, Z = 4, a = 16.4136(3)A; b = 27.6277(4)A; c = 16.7182(1)A; beta = 105.644(1) degrees). Each compound shows that the intercalated cation, Ag+ or Tl+, coordinates to a distorted trigonal prism of six AuI atoms. The counteranions reside well apart from the cations between the cluster chains. PMID- 11196851 TI - Through-ring bonding in edge sharing dimers of octahedral complexes. AB - A study of the preferred structures for the M2X2 rings in the binuclear complexes of types [M2(mu-XR2)2L8] and [M2(mu-XR3)2L8] is presented, based on qualitative orbital arguments supported by extended Huckel calculations on Cr compounds. The main conclusions are confirmed by DFT calculations on key compounds of Cr and Mn and agree well with the results of a structural database analysis. With the simplified electron counting scheme deduced, complexes with six or four electrons available for bonding of the M2X2 framework are predicted to have two possible minimum energy structures, with either a short M-M or X-X distance, whereas compounds with eight framework electrons are expected to present no short through ring distance. Such a behavior is consistent with the framework electron rules reported earlier for compounds with different coordination spheres and provides a general description of the structure and bonding in a variety of compounds with M2X2 diamonds. Metal-metal bonding across the ring can be equally predicted taking into account only the bonding characteristics of the t2g-like orbitals for the XR2- but not for the XR3-bridged complexes. In addition, the framework electron counting scheme has the advantage of being independent of the formal oxidation state assigned to the metal atom. PMID- 11196852 TI - Syntheses, structures, and physical properties of LnAsTe (Ln = La, Pr, Sm, Gd, Dy, Er). AB - Six rare-earth arsenic tellurides have been synthesized by the reactions of the rare-earth elements (Ln) with As and Te at 1123 K. LaAsTe (a = 7.8354(11) A, b = 4.1721(6) A, c = 10.2985(14) A, T = 153 K), PrAsTe (a = 7.728(2) A, b = 4.1200(11) A, c = 10.137(3) A, T = 153 K), SmAsTe (a = 7.6180(16) A, b = 4.0821(9) A, c = 9.991(2) A, T = 153 K), GdAsTe (a = 7.5611(15) A, b = 4.0510(8) A, c = 9.920(2) A, T = 153 K), DyAsTe (a = 7.4951(13) A, b = 4.0246(7) A, c = 9.8288(17) A, T = 153 K), and ErAsTe (a = 7.4478(1) A, b = 4.0078(1) A, c = 9.7552(2) A, T = 153 K) crystallize with four formula units in the orthorhombic space group D2h16-Pnma. These compounds are isostructural and belong to the beta ZrSb2 structure type. In each compound, the Ln atoms are coordinated by a tricapped trigonal prism of four As atoms and five Te atoms. The entire three dimensional structure is built up by the motif of the LnAs4Te5 tricapped trigonal prisms. Infinite nonalternating zigzag As chains are found along the b axis, with As-As distances in these compounds ranging from 2.5915(5) to 2.6350(9) A. Conductivity measurements in the direction of these As chains indicate that PrAsTe is metallic whereas SmAsTe and DyAsTe are weakly metallic. Antiferromagnetic transitions occur in SmAsTe and DyAsTe at 3 and 9 K, respectively. DyAsTe above 9 K follows the Curie-Weiss law. PMID- 11196853 TI - Water adsorption and hydrolysis on molecular transition metal oxides and oxyhydroxides. AB - Addition of water to molecular transition metal oxides (TiO2(g) and CrO3(g)) and oxyhydroxides (ScO(OH)(g), VO2(OH)(g), and MnO3(OH)(g)) was studied by means of quantum chemistry. In the investigated reactions, each reaction step comprised the breaking of one M=O bond and the formation of two OH groups. Exothermicity was observed when the product had tetrahedral or lower oxygen coordination. The reactions were found to involve stable water complexes as intermediates. The stabilities of such complexes were accentuated in the addition reaction Sc(OH)3(g) + H2O(g), in which the formation of a tetrahedral complex was found exothermic. For VO(OH)3(g), CrO2(OH)2(g), and MnO3(OH)(g), water addition to the remaining M=O bonds was found endothermic, whereas the formation of water complexes, using hydrogen bonds and preserving the oxyhydroxide kernel, was preferred. Thus, the sequence of such kernels for water clustering in the investigated reactions was found to be Sc(OH)3.H2O(g), Ti(OH)4(g), VO(OH)3(g), CrO2(OH)2(g), and MnO3(OH)(g). These stability considerations are important, as CrO2(OH)2(g) is believed to be the product of water-induced degradation of the protective chromium oxide scale on stainless steel at elevated temperatures. PMID- 11196854 TI - Hydrolysis on transition metal oxide clusters and the stabilities of M-O-M bridges. AB - Water addition to molecular single, double and triple M-O-M bridges (M = Sc, Ti, V, Cr, and Mn) were considered, and the stabilities toward stepwise hydrolysis of the oxygen bridges were studied by means of quantum chemistry. The M-O bond distances for the studied systems were compared to experiment for demonstration of the applicability of the B3LYP functional to the investigated systems. While substantial exothermicities were found for the hydrolysis of double and triple M O-M bridges, addition of water to a single bridge was generally found to be slightly endothermic. The lack of enthalpy drive for the (OH)yOxM-O-MOx(OH)y + H2O-->2MOx-1(OH)y+2 reaction was taken to suggest that entropy increase and the formation of mononuclear water complexe, would be decisive factors for the dissociation. A mechanism was proposed for the observed erosion of the protective chromium oxide scale on high-temperature alloys at elevated temperatures and high humidities, based on the formation of CrO2(OH)2(g). PMID- 11196855 TI - Selective imidazolidine ring opening during complex formation of iron(III), copper(II), and zinc(II) with a multidentate ligand obtained from 2 pyridinecarboxaldehyde N-oxide and triethylenetetramine. AB - The condensation of 2-pyridinecarboxaldehyde N-oxide and triethylenetetramine yields a product with two imidazolidine rings, as proven by a solid-state X-ray structure analysis as well as by NMR solution spectra. This ligand, L1, undergoes a ring-opening reaction on complex formation with Cu(II), yielding [CuL2]2+ where L2 functions as a pentadentate ligand, containing only one imidazolidine ring. On complexation with Zn(II) and Fe(III), both rings are opened and the complexes [ZnL3]2+ and [FeL3]3+ with a hexadentate L3 ligand are formed. The recrystallization of [ZnL3]2+ from DMSO solution results in the complex [ZnL1(DMSO)2]2+ in which L1 behaves as a tetradentate ligand. Thus L1, L2, and L3 are structural isomers with two, one, or no imidazolidine rings, as confirmed by X-ray structure analyses. The intramolecular ring formation is the result of the nucleophilic addition of the N(amino) group to the electrophilic sp2-hybridized HC delta+=N site. Owing to the absence of the chelate effect on the sp3 hybridized carbon atom belonging to the imidazolidine ring, the ring opening is facilitated and readily observed upon complex formation with Cu(II), Zn(II), and Fe(III). PMID- 11196856 TI - Reactivity of "Eu(OiPr)2" with phenols: formation of linear Eu3, square pyramidal Eu5, cubic Eu8, and capped cubic Eu9 polymetallic europium complexes. AB - The direct reaction of europium with 2-propanol and phenols has been investigated under a variety of conditions. The reaction of europium metal with 2,6 dimethylphenol and 2,6-diisopropylphenol in 2-propanol at reflux revealed that polymetallic europium complexes could be generated by this method. Hx[Eu8O6(OC6H3Me2-2,6)12(OiPr)8], 1, and H5[Eu5O5(OC6H3iPr2-2,6)6(NCCH3)8], 2, were isolated by recrystallization in the presence of hexanes and acetonitrile, respectively, and characterized by X-ray crystallography. Complex 1 has a cubic arrangement of europium ions with face-bridging mu 4-O donor atoms, edge-bridging mu-O(phenoxide/phenol) ligands, and terminal O(isopropoxide/2-propanol) ligands. Complex 2 is mixed valent and has a square pyramidal europium core with four Eu(II) ions at the basal positions and one Eu(III) ion at the apex. Since these reactions gave complicated mixtures of products from which 1 and 2 could only be obtained in low yields, direct reactions under less forcing reaction conditions were investigated. Europium reacts slowly at room temperature to form arene soluble divalent [Eu(OiPr)2(THF)x]n, 3. Complex 3 reacts with 2,6-dimethylphenol to form the arene-insoluble complex (H[Eu(OC6H3Me2)2(OiPr)])n, 4. Recrystallization of 4 in the presence of THF results in the crystallographically characterizable divalent trimetallic complex [Eu(OC6H3Me2-2,6)2(THF)2]3, 5, which has an unusual linear metal geometry. In the presence of HOiPr at ambient conditions in the glovebox, crystals of 5 slowly convert to the mixed valent H10[Eu8O8(OC6H3Me2-2,6)10(OiPr)2(THF)6], 6, which was found to have a cubic arrangement of europium atoms similar to 1 by X-ray crystallography. Complex 4, upon heating under vacuum, followed by reaction with THF, forms the arene-soluble divalent complex H18([Eu9O8(OC6H3Me2-2,6)10(THF)7][Eu9O9(OC6H3Me2-2,6)10(THF)6]), 7, which contains two types of capped cubic arrangements of europium ions in the solid state. PMID- 11196857 TI - Magnetic coupling in end-to-end azido-bridged copper and nickel binuclear complexes: a theoretical study. AB - The influence of structural parameters on the exchange coupling J between metal atoms in end-to-end azido-bridged binuclear complexes of Cu(II) and Ni(II) has been studied by means of density functional calculations. For the case of double bridged Cu(II) compounds, four ideal pentacoordinate models have been employed in which the coordination spheres of the two metal atoms are either a trigonal bipyramid or a square pyramid, connected through equatorial or axial bridges. The distortion from those ideal geometries along a Berry pathway has also been analyzed. For the hexacoordinate Ni(II) compounds, models with two or one bridging ligands have been studied. The effect of the bridging M-N-N bond angles on the exchange coupling has been analyzed for both the Cu(II) and Ni(II) complexes. PMID- 11196858 TI - A hydrothermal investigation of the 1/2V2O5-H2C2O4/H3PO4/NH4OH system: synthesis and structures of (NH4)VOPO(4).1.5H2O, (NH4)0.5VOPO(4).1.5H2O, (NH4)2[VO(H2O)3]2[VO(H2O)][VO(PO4)2](2).3H2O, and (NH4)2[VO(HPO4)]2(C2O4).5H2O. AB - The 1/2V2O5-H2C2O4/H3PO4/NH4OH system was investigated using hydrothermal techniques. Four new phases, (NH4)VOPO(4).1.5H2O (1), (NH4)0.5VOPO(4).1.5H2O (2), (NH4)2[VO(H2O)3]2[VO(H2O)][VO(PO4)2]2.3H2O (3), and (NH4)2[VO(HPO4)]2(C2O4).H2O (4), have been prepared and structurally characterized. Compounds 1 and 2 have layered structures closely related to VOPO(4).2H2O and A0.5VOPO4.yH2O (A = mono- or divalent metals), whereas 3 has a 3D open-framework structure. Compound 4 has a layered structure and contains both oxalate and phosphate anions coordinated to vanadium cations. Crystal data: (NH4)VOPO(4).1.5H2O, tetragonal (I), space group I4/mmm (No. 139), a = 6.3160(5) A, c = 13.540(2) A, Z = 4; (NH4)0.5VOPO(4).1.5H2O, monoclinic, space group P2(1)/m (No. 11), a = 6.9669(6) A, b = 17.663(2) A, c = 8.9304(8) A, beta = 105.347(1) degrees, Z = 8; (NH4)2[VO(H2O)3]2[VO(H2O)][VO(PO4)2]2.3H2O, triclinic, space group P1 (No. 2), a = 10.2523(9) A, b = 12.263(1) A, c = 12.362(1) A, alpha = 69.041(2) degrees, beta = 65.653(2) degrees, gamma = 87.789(2) degrees, Z = 2; (NH4)2[VO(HPO4)]2(C2O4).5H2O, monoclinic (C), space group C2/m (No. 12), a = 17.735(2) A, b = 6.4180(6) A, c = 22.839(2) A, beta = 102.017(2) degrees, Z = 6. PMID- 11196859 TI - Formation of a tetranuclear copper (II) cluster assembled by metal-assisted hydrolysis and desulfurization of bis(3,5-dimethylpyrazolyl)methylphosphine sulfide, MeP(S)(3,5-Me2Pz)2. AB - The reaction of methylphosphine sulfide, MeP(S)(3,5-Me2Pz)2, 1, with anhydrous CuCl2 affords a tetranuclear copper cluster[Cu2Cl2(3,5-Me2Pz)3(MePO3)]2, 2, and a dinuclear compound Cu2Cl4(3,5-Me2Pz)4, 3. This reaction involves a metal-assisted desulfurization along with concomitant hydrolysis of P-N bonds. The X-ray structures of 1-3 have been determined, and the crystal parameters for these are the following. 1: space group = C2/c, a = 15.2552(1) A, b = 8.7364(2) A, c = 21.4490(3) A, beta = 93.349(1) degrees, V = 2853.74(8) A3, and Z = 8. 2: space group = P2(1)/n, a = 12.5964(4) A, b = 15.7773(4) A, c = 13.9781(4) A, beta = 116.6280(10) degrees, V = 2483.32(12) A3, and Z = 2. 3: space group = P2(1)/c, a = 8.7137(8) A, b = 13.5493(14) A, c = 11.8847(12) A, beta = 106.179(2) degrees, V = 1347.6(2) A3, and Z = 2. The structure of 2 shows that it comprises two dinuclear copper cores bridged together by two tripodal methylphosphinate, MePO3, ligands. 2 is weakly antiferromagnetically coupled, as revealed by variable temperature magnetic susceptibility measurements. PMID- 11196860 TI - Self-propagating metathesis routes to metastable group 4 phosphides. AB - Group 4 phosphides, which are typically prepared at high temperatures (> 800 degrees C) over several days, are synthesized in self-propagating metathesis (exchange) reactions in seconds. These reactions produce cubic forms of zirconium phosphide (ZrP) and hafnium phosphide (HfP) which are normally made at temperatures greater than 1425 degrees C and 1600 degrees C, respectively. To test whether the high temperatures reached in the metathesis reactions are responsible for the formation of the cubic phases, inert salts are added to lower the maximum reaction temperatures. The lower temperature reactions still result in cubic phosphides, although smaller crystallites form. Further experiments with phosphorus addition indicate that the phosphorus content is not responsible for cubic phase formation. Templating is ruled out using lattice mismatched KCl and hexagonal ZnS as additives. Therefore, the direct synthesis of the high temperature cubic phase in metathesis reactions appears to be caused by nucleation of the metastable cubic form that is then trapped by rapid cooling. Heating the cubic phase of either ZrP or HfP to 1000 degrees C for 18 h, or carrying out metathesis reactions in sealed ampules at 1000 degrees C, results only in the hexagonal phase. PMID- 11196861 TI - Peroxo and ferryl intermediates detected by 1H NMR spectroscopy during the oxygenation of iron(II) porphycene. AB - The iron(III) 2,7,12,17-tetra-n-propylporphycene (TPrPc)FeIIICl is reduced using aqueous sodium dithionite or zinc amalgam to produce (TPrPc)FeII. The 1H NMR spectrum of (TPrPc)FeII (293 K; delta (ppm): pyrrole, -37.52; meso, 71.56; alpha CH2, 27.47; beta-CH2, 8.92; gamma-CH3, 5.55) can be accounted for by the planar unligated iron(II) porphycene with an S = 1 ground electronic state. Introduction of dioxygen into a toluene-d8 solution of (TPrPc)FeII at 203 K results in the formation of the (mu-peroxo)diiron(III) porphycene (TPrPc)FeIII-O-O-FeIII(TPrPc). The value of the chemical shift of the pyrrole resonances (17.99 ppm at 203 K) of this species and its distinct non-Curie behavior imply strong antiferromagnetic iron(III)-iron(III) coupling via a mu-peroxo bridge. The (TPrPc)FeIII-O-O FeIII(TPrPc) intermediate is stable at 203 K, but it converts into the (mu oxo)diiron complex (TPrPc)FeIII-O-FeIII(TPrPc) upon warming above 203 K. Reaction of (TPrPc)FeIII-O-O-FeIII(TPrPc) with a nitrogen bases (B: pyridine-d5, 1 methylimidazole) results in a homolytic cleavage of the mu-peroxo bridge to form the ferryl porphycene complex B(TPrPc)FeIVO (1H NMR (223 K), delta (ppm): pyrrole, -1.32; meso, 11.80). B(TPrPc)FeIVO reacts with triphenylphosphine at 223 K to yield triphenylphosphine oxide. PMID- 11196862 TI - Structural influences of organonitrogen ligands on vanadium oxide solids. Hydrothermal syntheses and structures of the terpyridine vanadates [V2O4(terpy)2]3[V10O28], [VO2(terpy)][V4O10], and [V9O22(terpy)3]. AB - Hydrothermal reactions of the V2O5/2,2':6':2"-terpyridine/ZnO/H2O system under a variety of conditions yielded the organic-inorganic hybrid materials [V2O4(terpy)2]3[V10O28].2H2O (VOXI-10), [VO2(terpy)][V4O10] (VOXI-11), and [V9O22(terpy)3] (VOXI-12). The structure of VOXI-10 consists of discrete binuclear cations [V2O4(terpy)2]2+ and one-dimensional chains [V10O28]6-, constructed of cyclic [V4O12]4- clusters linked through (VO4) tetrahedra. In contrast, the structure of VOXI-11 exhibits discrete mononuclear cations [VO2(terpy)]1+ and a two-dimensional vanadium oxide network, [V4O10]1-. The structure of the oxide layer is constructed from ribbons of edge-sharing square pyramids; adjacent ribbons are connected through corner-sharing interactions into the two-dimensional architecture. VOXI-12 is also a network structure; however, in this case the terpy ligand is incorporated into the two-dimensional oxide network whose unique structure is constructed from cyclic [V6O18]6- clusters and linear (V3O5(terpy)3) moieties of corner-sharing vanadium octahedra. The rings form chains through corner-sharing linkages; adjacent chains are connected through the trinuclear units. Crystal data: VOXI-10, C90H70N18O42V16, triclinic P1, a = 12.2071(7) A, b = 13.8855(8) A, 16.9832(10) A, alpha = 69.584(1) degrees, beta = 71.204(1) degrees, gamma = 84.640(1) degrees, Z = 1; VOXI-11, C15H11N3O12V5, monoclinic, P2(1)/n, a = 7.7771(1) A, b = 10.3595(2) A, c = 25.715(4) A, beta = 92.286(1) degrees, Z = 4; VOXI-12, C45H33N9O22V9, monoclinic C2/c, a = 23.774(2) A, b = 9.4309(6) A, c = 25.380(2) A, beta = 112.047(1) degrees, Z = 4. PMID- 11196863 TI - Oxidative scission of a Mo-Mo quadruple bond. AB - Two compounds containing the cations Mo2(DPhIP)4n+, n = 1 or 2 and DPhIP = the anion of 2,6-diphenyliminopiperidine, have been obtained by oxidation of the quadruply-bonded Mo2(DPhIP)4 species. The first oxidation process conserves the structure but results in a slight increase of the Mo-Mo distance from 2.114(1) to 2.136(2) A in [Mo2(DPhIP)4](PF6).2CH2Cl2 (1.2CH2Cl2). However, the second oxidation process breaks the dimolybdenum bond, giving a bioctahedral complex, [Mo2(DPhIP)4](BF4)2.5CH3CN.Et2O (2.5CH3CN.Et2O), with Mo...Mo separation of 2.9954(7) A. Crystallographic data for 1.2CH2Cl2 are space group C2/c, a = 17.1891(9) A, b = 17.807(1) A, c = 24.210(2) A, beta = 106.403(4) degrees, Z = 4; for 2.5CH3CN.Et2O, space group P2(1)/n, a = 16.523(5) A, b = 27.418(5) A, c = 18.163(3) A, beta = 93.48(2) degrees, Z = 4. PMID- 11196864 TI - Preparations, structures, and electrochemical studies of aryldiazene complexes of rhenium: syntheses of the first heterobinuclear and heterotrinuclear derivatives with bis(diazene) or bis(diazenido) bridging ligands. AB - The mono- and binuclear aryldiazene complexes [Re(C6H5N=NH)(CO)5-nPn]BY4 (1-5) and [(Re(CO)5-nPn)2-(mu-HN=NAr-ArN=NH)](BY4)2 (6-12) [P = P(OEt)3, PPh(OEt)2, PPh2OEt; n = 1-4; Ar-Ar = 4,4'-C6H4-C6H4, 4,4'-(2-CH3)C6H3-C6H3(2-CH3), 4,4'-C6H4 CH2-C6H4; Y = F, Ph) were prepared by reacting the hydride species ReH(CO)5-nPn with the appropriate mono- and bis(aryldiazonium) cations. These compounds, as well as other prepared compounds, were characterized spectroscopically (IR; 1H, 31P, 13C, and 15N NMR data), and 1a was also characterized by an X-ray crystal structure determination. [Re(C6H5N=NH)(CO)(P(OEt)3)4]BPh4 (1a) crystallizes in space group P1 with a = 15.380(5) A, b = 13.037(5) A, c = 16.649(5) A, alpha = 90.33(5) degrees, beta = 91.2(1) degrees, gamma = 89.71(9) degrees, and Z = 2. The "diazene-diazonium" complexes [M(CO)3P2(HN=NAr-ArN identical to N)](BF4)2 (13 15, 17) [M = Re, Mn; P = PPh2OEt, PPh2OMe, PPh3; Ar-Ar = 4,4'-C6H4-C6H4, 4,4' C6H4-CH2-C6H4] and [Re(CO)4(PPh2OEt)(4,4'-HN=NC6H4-C6H4N identical to N)](BF4)2 (16b) were synthesized by allowing the hydrides MH(CO)3P2 or ReH(CO)4P to react with equimolar amounts of bis(aryldiazonium) cations under appropriate conditions. Reactions of diazene-diazonium complexes 13-17 with the metal hydrides M2H2P'4 and M2'H(CO)5-nP"n afforded the heterobinuclear bis(aryldiazene) derivatives [M1(CO)3P2(mu-HN=NAr-ArN=NH)M2HP'4](BPh4)2 (ReFe, ReRu, ReOs, MnRu, MnOs) and [M1(CO)3P2(mu-HN=NAr-ArN=NH)M2'(CO)5-nP"n](BPh4)2 (ReMn, MnRe) [M1 = Re, Mn; M2 = Fe, Ru, Os; M2' = Mn, Re; P = PPh2OEt, PPh2OMe; P',P" = P(OEt)3, PPh(OEt)2; Ar-Ar = 4,4'-C6H4-C6H4, 4,4'-C6H4-CH2-C6H4; n = 1, 2]. The heterotrinuclear complexes [Re(CO)3(PPh2OEt)2(mu-4,4'-HN=NC6H4 C6H4N=NH)M(P(OEt)3)4(mu-4,4'-HN=NC6H4- C6H4N=NH)Mn(CO)3(PPh2OEt)2](BPh4)4 (M = Ru, Os) (ReRuMn, ReOsMn) were obtained by reacting the heterobinuclear complexes ReRu and ReOs with the appropriate diazene-diazonium cations. The heterobinuclear complex with a bis(aryldiazenido) bridging ligand [Mn(CO)2(PPh2OEt)2(mu-4,4' N2C6H4-C6H4N2)Fe(P(OEt)3)4]BPh4 (MnFe) was prepared by deprotonating the bis(aryldiazene) compound [Mn(CO)3(PPh2OEt)2(mu-4,4'-HN=NC6H4-C6H4N=NH)Fe(4- CH3C6H4CN)(P(OEt)3)4](BPh4)3. Finally, the binuclear compound [Re(CO)3(PPh2OEt)2(mu-4,4'-HN=NC6H4-C6H4N2)Fe(CO)2(P(OPh)3)2](BPh4)2 (ReFe) containing a diazene-diazenido bridging ligand was prepared by reacting [Re(CO)3(PPh2OEt)2(4,4'-HN=NC6H4-C6H4N identical to N)]+ with the FeH2(CO)2(P(OPh)3)2 hydride derivative. The electrochemical reduction of mono- and binuclear aryldiazene complexes of both rhenium (1-12) and the manganese, as well as heterobinuclear ReRu and MnRu complexes, was studied by means of cyclic voltammetry and digital simulation techniques. The electrochemical oxidation of the mono- and binuclear aryldiazenido compounds Mn(C6H5N2)(CO)2P2 and (Mn(CO)2P2)2(mu-4,4'-N2C6H4-C6H4N2) (P = PPh2OEt) was also examined. Electrochemical data show that, for binuclear compounds, the diazene bridging unit allows delocalization of electrons between the two different redox centers of the same molecule, whereas the two metal centers behave independently in the presence of the diazenido bridging unit. PMID- 11196865 TI - Synthesis of monohalogeno derivatives of closo-[B9H9]2-. Crystal structures of (Ph4P)2[1-XB9H8].CH3CN (X = Cl, Br, I). AB - By reaction of Na2[B9H9] with the appropriate N-halogenosuccinimide, the monohalogenated anion [1-XB9H8]2- (X = Cl, Br, or I) is formed. The X-ray diffraction analyses performed on single crystals of (Ph4P)2[1-XB9H8].CH3CN (X = Cl, Br, I) reveal that the tricapped trigonal prismatic geometry of the cluster is retained after substitution in the 1-position. Crystallographic data are as follows for (Ph4P)2[1-XB9H8].CH3CN. X = Cl, Br: monoclinic, space group P2(1), a = 10.7 A, b = 32.9 A, c = 13.8 A, beta = 96 degrees, Z = 4, R1 = 0.038 and R1 = 0.036, respectively. X = I: monoclinic, space group P2(1)/n, a = 10.5 A, b = 13.6 A, c = 33.4 A, beta = 94 degrees, Z = 4, R1 = 0.094. The compounds have been characterized by vibrational and 11B NMR spectroscopy as well. PMID- 11196866 TI - Diazo complexes of rhenium: preparations and crystal structures of the bis(dinitrogen), [Re(N2)2(PPh(OEt)2)4][BPh4] and methyldiazenido [ReCl(CH3N2)(CH3NHNH2)(PPh(OEt)2)3][BPh4] derivatives. AB - Depending on experimental conditions and the nature of the hydrazine, the reactions of ReCl3P3 [P = PPh(OEt)2] with RNHNH2 (R = H, CH3, tBu) afford the bis(dinitrogen) [Re(N2)2P4]+ (2+), dinitrogen ReClN2P4 (3), and methyldiazenido [ReCl(CH3N2)(CH3NHNH2)P3]+ (1+) derivatives. In contrast, reactions of ReCl3P3 [P = PPh(OEt)2, PPh2OEt] with arylhydrazines ArNHNH2 (Ar = Ph, p-tolyl) give the aryldiazenido cations [ReCl(ArN2)(ArNHNH2)P3]+ (4+) and [ReCl(ArN2)P4]+ (7+) and the bis(aryldiazenido) cations [Re(ArN2)2P3]+ (5+, 6+). These complexes were characterized spectroscopically (IR; 1H and 31P NMR), and the BPh4 complexes 1, 2, and 7 were characterized crystallographically. The methyldiazenido derivative [ReCl(CH3N2)(CH3NHNH2)(PPh(OEt)2)3][BPh4] (1) crystallizes in space group P1 with a = 15.396(5) A, b = 16.986(5) A, c = 11.560(5) A, alpha = 93.96(5) degrees, beta = 93.99(5) degrees, gamma = 93.09(5) degrees, and Z = 2 and contains a singly bent CH3N2, group bonded to an octahedral central metal. One methylhydrazine ligand, one Cl- trans to the CH3N2, and three PPh(OEt)2 ligands complete the coordination. The complex [Re(N2)2(PPh(OEt)2)4][BPh4] (2) crystallizes in space group Pbaa with a = 23.008(5) A, b = 23.367(5) A, c = 12.863(3) A, and Z = 4. The structure displays octahedral coordination with two end-on N2 ligands in mutually trans positions. [ReCl(PhN2)(PPh(OEt)2)4][BPh4] (7) crystallizes in space group P2(1)/n with a = 19.613(5) A, b = 20.101(5) A, c = 19.918(5) A, beta = 115.12(2) degrees, and Z = 4. The structure shows a singly bent phenyldiazenido group trans to the Cl- ligand in an octahedral environment. The dinitrogen complex ReClN2P4 (3) reacts with CF3SO3CH3 to give the unstable methyldiazenido derivative [ReCl(CH3N2)P4][BPh4]. Reaction of the methylhydrazine complex [ReCl(CH3N2)(CH3NHNH2)P3][BPh4] (1) with Pb(OAc)4 at -30 degrees C results in selective oxidation of the hydrazine, affording the corresponding methyldiazene derivative [ReCl(CH3N=NH)(CH3N2)P3][BPh4] (8). In contrast, treatment with Pb(OAc)4 of the related arylhydrazines [ReCl(ArN2)(ArNHNH2)P3][BPh4] (4) [P = PPh(OEt)2] gives the bis(aryldiazenido) complexes [Re(ArN2)2P3][BPh4] (5). Possible protonation reactions of Bronsted acids HX with all diazenides, 1, 4, 5, 6, and 8, were investigated and found to proceed only in the cases of the bis(aryldiazenido) complexes 5 and 6, affording, with HCl, the octahedral [ReCl(ArN=NH)(ArN2)P3][BPh4] or [ReCl(Ar(H)NN)(ArN2)P3][BPh4] (10) (Ar = Ph; P = PPh2OEt) derivative. PMID- 11196867 TI - Syntheses, structures, and properties of tetrakis(mu-acetato)dirhodium(II) complexes with axial pyridine nitrogen donor ligands with or without assistance of hydrogen bonds. AB - Eight adducts of Rh2(O2CCH3)4 with axial pyridine derivatives that contain hydrogen-bonding amino and/or steric methyl substituents in the 2- and 6 positions have been prepared and examined by electronic absorption and 1H NMR spectroscopy in solution and by elemental, IR, thermogravimetric, and X-ray diffraction analyses in the solid state. The results indicated that strong hydrogen bonding interactions between Rh2(O2CCH3)4 and axially coordinated pyridine derivatives with a 2- or 6-amino group occur in both solution and the solid state and contribute to the higher thermal stability of the molecular assembly of dirhodium complexes. It was demonstrated that such a combination of coordinate and hydrogen bonds is useful as a building tool in designing and constructing new organic-inorganic hybridized compounds and supramolecular architectures. PMID- 11196868 TI - Synthesis and characterization of water-soluble silver(I) complexes with L histidine (H2his) and (S)-(-)-2-pyrrolidone-5-carboxylic acid (H2pyrrld) showing a wide spectrum of effective antibacterial and antifungal activities. Crystal structures of chiral helical polymers [Ag(Hhis)]n and ([Ag(Hpyrrld)]2)n in the solid state. AB - Two water-soluble, silver(I) complexes showing a wide spectrum of effective antibacterial and antifungal activities, i.e., ([Ag(Hhis)].0.2EtOH)2 (1; H2his = L-histidine) and [Ag(Hpyrrld)]2 (3; H2pyrrld = (S)-(-)-2-pyrrolidone-5-carboxylic acid) were prepared. In aqueous solution 1 and 3 were present as dimers, whereas in the solid state they were polymers. Crystallization of 1 by slow evaporation and/or vapor diffusion gave water-insoluble crystals of [Ag(Hhis)]n (2) showing modest antimicrobial activities. The complex 1 in the solid state is a polymer formed by intermolecular hydrogen-bonding interactions between dimeric [Ag(Hhis)]2 cores, while 2 is a different polymer without a core complex. X-ray crystallography revealed that 2 was a left-handed helical polymer consisting of a bent, 2-coordinate silver(I) atom bonding to the Namino atom of one Hhis- ligand and the N pi atom of a different Hhis- ligand. Of particular note is the fact that Ocarboxyl atoms do not participate in the coordination. X-ray crystallography also revealed that 3 was a left-handed helical polymer formed by self-assembly of dimeric [Ag(Hpyrrld)]2 cores with an intramolecular metal(I) metal(I) interaction (Ag-Ag distance, 2.9022(7) A). The FT-IR and the solid-state 13C and 15N NMR spectra showed that the dimeric core of 1 was formed through Ag-N bonds, while that of 3 was formed through Ag-O bonds. The molecular ions of 1 and 3 were detected by the positive-ion electrospray ionization (ESI) mass spectrometry. For 1-3, characterization by elemental analysis, TG/DTA, FT-IR, and variable-temperature solid-state 13C NMR and room-temperature 15N NMR measurements was performed, and for 1 and 3, that by solution molecular weight measurements and solution (109Ag, 1H, and 13C) NMR spectroscopies was also carried out. The antibacterial and antifungal activities of 1 and 3 were remarkable and comparable to those of the previous silver(I)-N-heterocycle complexes. PMID- 11196869 TI - Corroles with group 15 metal ions. Synthesis and characterization of octaethylcorroles containing As, Sb, and Bi ions in +3, +4, and oxidation states. AB - The synthesis, spectroscopic characterization, and electrochemistry of As, Sb, and Bi corroles are reported. The investigated complexes are represented by [(OEC)AsV(CH3)]+ClO4- and (OEC)M where M = As(III), Sb(III), or Bi(III) and OEC is the trianion of octaethylcorrole. The products of each redox reaction are characterized by UV-vis and ESR spectroscopy. The first one-electron oxidations of (OEC)As and (OEC)Sb are metal-centered and result in the formation of [(OEC)AsIV]+ and [(OEC)SbIV]+. A second one-electron oxidations generates [(OEC)AsV]2+ and [(OEC.)SbIV]2+, the latter of which is slowly converted to a Sb(V) corrole, [(OEC)SbV]2+. The first one-electron oxidation of (OEC)Bi leads only to the Bi(III) pi-cation radical, but a second one-electron oxidation is proposed to give a Bi(IV) complex, [(OEC)Bi]2+. The first reduction of [(OEC)AsV(CH3)]+ClO4- is accompanied by loss of the sigma-bonded methyl ligand and formation of an As(III) complex. PMID- 11196870 TI - Synthesis and characterization of the layered vanadium borophosphate (imidazolium)3.8(H3O)1.2[(VO)4(BO)2(PO4)5].0.3H2O. AB - The first layered vanadium borophosphate (imidazolium)3.8(H3O)1.2[(VO)4(BO)2(PO4)5].0.3H2O (1) has been synthesized hydrothermally and characterized by chemical analysis, infrared and Raman spectroscopy, and thermogravimetric and magnetic measurements. The compound crystallizes in the monoclinic space group C2/c, a = 9.4737 (5) A, b = 22.1444 (12) A, c = 17.2192 (13) A, beta = 105.936 (1) degrees, Z = 4. The structure contains a novel borophosphate secondary building unit, [B2P5O22], in which two BP2O10 trimers are linked by an additional PO4 tetrahedron. These units are connected by V(IV)2O8 dimers and V(IV)O5 square pyramids to form layers. The space between the layers is filled by disordered imidazolium and hydronium cations and water molecules that form a complex network of hydrogen bonds. A model for the interlayer disorder is proposed. PMID- 11196871 TI - Syntheses, characterizations, and single-crystal X-ray structures of soluble titanium alkoxide phosphonates. AB - Reactions of Ti(OiPr)4 with different phosphonic acids RPO3H2 (R = Ph, 4-CNPh, Me, tBu) in organic solvents have been investigated. In the presence of small amounts of water, the new molecular titanium oxide alkoxide phosphonates [Ti4(mu 3-O)(OiPr)5(mu-OiPr)3(RPO3)3].DMSO [R = Ph (1), Me (2), tBu (3), 4-CNPh (4)] were isolated. The single-crystal X-ray structure analyses of 1 and 2 revealed hexacoordinated titanium atoms and a connectivity of (111) for each phosphonate. Under rigorous exclusion of water, the reaction of Ti(OiPr)4 with tert butylphosphonic acid in toluene gave the titanium phosphonate tetramer [Ti(OiPr)2(tBuPO3)]4 (5). A single-crystal X-ray structure analysis of 5 revealed a 5 + 1 coordination of the titanium atoms as a result of the (112) connectivity of each phosphonate; such a coordination mode has never been reported for a titanium phosphate, phosphonate, or phosphinate. Compounds 1-5 were characterized by FT-IR, 31P MAS NMR, and solution multinuclear NMR (1H, 13C(1H,) 31P(1H)) spectroscopies. 13C CP MAS NMR experiments were carried out on arylphosphonates 1 and 4. Solution NMR experiments were also used to investigate the exchange reaction between 1 and 2 and the conversion of 5 to [Ti4(mu 3-O)(OiPr)5(mu OiPr)3(tBuPO3)3].iPrOH by partial hydrolysis in the presence of Ti(OiPr)4. The phosphonate clusters 1-5 are soluble in organic solvents and are likely intermediates in the sol-gel processing of inorganic-organic hybrids based on titanium oxide and phosphonate groups that we are currently developing. PMID- 11196872 TI - Synthesis and characterization of sulfide, sulfide-sulfonium, and bissulfide derivatives of [B12H12]2-. Additivity of Me2S and MeS- substituent effects in 11B NMR spectra of disubstituted icosahedral boron clusters. AB - The 1,2-, 1,7-, and 1,12-isomers of (Me2S)2B12H10 (O, M, and P) react with potassium phthalimide in DMF or EtSNa in CH3CN/EtOH upon reflux producing the corresponding isomers of [(MeS)(Me2S)B12H10]- (O1-, M1-, P1-). If excess of either nucleophile is used, [Me2SB12H11]- (1) and O, M, P can be converted into dianions [MeSB12H11]2- (2) and [(MeS)2B12H10]2- (O2-, M2-, P2-). The use of EtSNa is recommended since it facilitates the isolation of products compared to the potassium phthalimide method. When 1 or O, M, P are treated with an excess of an alkali metal (Na, K) in liquid ammonia at -40 degrees C, sulfide 2 or bissulfide dianions O2-, M2-, P2- are obtained cleanly and almost instantly. While both the nucleophilic substitution and alkali metal reduction methods are useful for the synthesis of dianions 2, O2-, M2-, and P2-, only the former method is suitable for the synthesis of the sulfide-sulfonium anions O1-, M1-, P1-. The analysis of the 11B NMR spectra of 1, O, M, P and anions derived from them demonstrated that the spectra of the disubstituted species can be predicted qualitatively, keeping in mind the simple substituent effects obtained from the spectra of monosubstituted anions 1 and 2. Some evidence is found for small partial double bond character of the B-SMe bonds in anions. [MePPh3]+ salts of [MeSB12H11]2- (2) and [1-(MeS)-7-(Me2S)B12H10]- (M1-) are structurally characterized by single crystal X-ray diffraction analysis. Crystal data: [MePPh3]2[MeSB12H11], P2(1) (No. 4), a = 9.243(1) A, b = 18.272(1) A, c = 12.548(1) A, beta = 103.17(1) degrees, Z = 2; [MePPh3][1-(MeS)-7-(Me2S)B12H10], P1 (No. 2), a = 9.278(2) A, b = 12.003(5) A, c = 14.819(7) A, alpha = 112.18(4) degrees, beta = 105.61(3) degrees, gamma = 92.91(3) degrees, Z = 2. PMID- 11196873 TI - Copper(II) and copper(I) complexes with an open-chain N4 Schiff base ligand modeling CuZn superoxide dismutase: structural and spectroscopic characterization and kinetics of electron transfer. AB - The structure of the complex [CuII(PuPy)](ClO4)2 (PuPy = L = 1,8-bis(2-pyridyl) 2,7-diazaoctadiene-1,7) and the structure of the corresponding copper(I) complex were determined. In CuIIL(ClO4)2, a model compound with CuZnSOD activity, the unit CuIIL2+ has a tetrahedrally distorted square-planar N4 coordination geometry. The copper(I) complex with L was found to be dimeric, (CuIL)2(ClO4)2.DMF (DMF = N,N-dimethylformamide). The binuclear unit (CuIL)2(2+) has a helical structure with two ligands L bridging the two copper atoms to provide tetrahedral N4 coordination of each copper(I). In solutions of (CuIL)2(ClO4)2.DMF, solvent-dependent dissociation occurs according to D reversible 2M (D = (CuIL)2(2+); M = CuILSx+; S = solvent). Stopped-flow spectrophotometry was used to determine the rate constants for the dissociation of the dimer D (kM) and dimerization of the monomer M (kD) for S = acetonitrile and DMF. Equilibrium constants Kdim = kM/kD were determined spectrophotometrically. In aqueous solution, the oxidation of the dimer (CuIL)2(2+) by CoIII(NH3)5Cl2+ and cis- and trans-CoIII(en)2Cl2+ follows a second order rate law, rate = kox[(CuIL)2(2+)][Co(III)]. Data for rate constant kox and for the activation parameters delta H++ and delta S++ are presented. In DMF, the oxidation of (CuIL)2(2+) by CoIII(NH3)5Cl2+ occurs via the monomer CuIL(DMF)x+ and the dissociation of (CuIL)2(2+) becomes rate-controlling. The reduction of CuIIL2+ by RuII(edta)H2O2- was found to be too fast to be resolved by stopped flow spectrophotometry. The kinetic results are discussed mechanistically in terms of the redox switch aspects of the system. PMID- 11196874 TI - Synthesis, characterization, and spontaneous resolution of chiral nickel(II) complexes with the tripod ligand tris[2-(((2-phenylimidazol-4 yl)methylidene)amino)ethyl]amine. AB - The chiral nickel(II) complexes of a tripod-type ligand with the chemical formulas [Ni(H3L)](NO3)2.MeOH (1), [Ni(H3L)](ClO4)2.MeOH (2), and [Ni(H3L)](C6H5COO)2.6H2O (3) were synthesized and characterized (H3L = tris[2 (((2-phenylimidazol-4-yl)methylidene)amino)ethyl]amine). The crystal structures of 1-3 were determined by their single-crystal X-ray analyses. 1, C37H40N12O7Ni: orthorhombic, P2(1)2(1)2(1); a = 14.198(2) A, b = 22.422(2) A, c = 12.019(2) A, Z = 4. 2, C37H40N10O9Cl2Ni: orthorhombic, P2(1)2(1)2(1); a = 14.206(2) A, b = 22.735(3) A, c = 12.696(3) A, Z = 4. 3, C50H58N10O10Ni: triclinic, P1; a = 14.191(5) A, b = 16.048(4) A, c = 13.692(4) A, alpha = 115.25(2) degrees, beta = 111.07(3) degrees, gamma = 64.75(2) degrees, Z = 2. Each complex has an octahedral coordination environment for the nickel(II) ion, formed by the six nitrogen donor atoms, and is either a delta (clockwise) or a lambda (anticlockwise) enantiomorph, depending on the screw arrangement of the tripod type ligand around the nickel(II) ion. The circular dichroism (CD) spectrum of a powdered sample of a crystal of 1 showed a positive and a negative peak at 915 and 630 nm, respectively, and that of another crystal showed an enantiomeric pattern. The observation of the Cotton effect and the crystal structure provided evidence for spontaneous resolution of the chiral complex molecule. PMID- 11196875 TI - 1,2-bis(pyridine-2-carboxamido)benzenate(2-), (bpb)2-: a noninnocent ligand. Syntheses, structures, and mechanisms of formation of [(n-Bu)4N][FeIV2(mu N)(bpb)2(X)2] (X = CN-, N3-) and the electronic structures of [MIII(bpbox1)(CN)2] (M = Co, Fe). AB - The well-known tetradentate ligand 1,2-bis(pyridine-2-carboxamido)benzenate(2-), (bpb)2-, and its 4,5-dichloro analogue, (bpc)2-, are shown to be "noninnocent" ligands in the sense that in coordination compounds they can exist in their radical one- and diamagnetic two-electron-oxidized forms (bpbox1)- and (bpbox2)0 (and (bpcox1)- and (bpcox2)0), respectively. Photolysis of high-spin [(n Bu)4N][FeIII(bpb)(N3)2] and its (bpc)2- analogue in acetone solution at room temperature generates the diamagnetic dinuclear complex [(n-Bu)4N][FeIV2(mu N)(bpb)2(N3)2] and its (bpc)2- analogue; the corresponding cyano complex [(n Bu)4N][FeIV2(mu-N)(bpb)2(CN)2] has been prepared via N3- substitution by CN-. Photolysis in frozen acetonitrile solution produces a low-spin ferric species (S = 1/2) which presumably is [FeIII(bpbox2)(N)(N3)]-, as has been established by EPR and Mossbauer spectroscopy. The mononuclear complexes [(n Bu)4N][FeIII(bpb)(CN2)] (low spin), [Et4N][CoIII(bpb)(CN)2] and Na[CoIII(bpc) (CN)2].3CH3OH can be electrochemically or chemically one-electron-oxidized to give [FeIII(bpbox1)(CN)2]0 (S = 0), [CoIII(bpbox1)(CN)2]0 (S = 1/2), and [CoIII(bpcox1)(CN)2]0 (S = 1/2). All complexes have been characterized by UV-vis, EPR, and Mossbauer spectroscopy, and their electro- and magnetochemistries have been studied. The crystal structures of [(n-Bu)4N][FeIII(bpb)(N3)2].1/2C6H6CH3, Na[FeIII(bpb)(CN)2], Na[CoIII(bpc)(CN)2].3CH3OH, [(n-Bu)4N][FeIV2(mu N)(bpb)2(CN)2], and [(n-Bu)4N][FeIV2(mu-N)(bpb)(N3)2] have been determined by single-crystal X-ray diffraction. PMID- 11196876 TI - Reactivity of mu-hydroxodizinc(II) centers in enzymatic catalysis through model studies. AB - The stable dinuclear complex [Zn2(BPAM)(mu-OH)(mu-O2PPh2)](ClO4)2, where BPAN = 2,7-bis[2-(2-pyridylethyl)-aminomethyl]-1,8-naphthyridine, was chosen as a model to investigate the reactivity of (mu-hydroxo)dizinc(II) centers in metallohydrolases. Two reactions, the hydrolysis of phosphodiesters and the hydrolysis of beta-lactams, were studied. These two processes are catalyzed in vivo by zinc(II)-containing enzymes: P1 nucleases and beta-lactamases, respectively. The former catalyzes the hydrolysis of single-stranded DNA and RNA. beta-Lactamases, expressed in many types of pathogenic bacteria, are responsible for the hydrolytic degradation of beta-lactam antibiotic drugs. In the first step of phosphodiester hydrolysis promoted by the dinuclear model complex, the substrate replaces the bridging diphenylphosphinate. The bridging hydroxide serves as a general base to deprotonate water, which acts as a nucleophile in the ensuing hydrolysis. The dinuclear model complex is only 1.8 times more reactive in hydrolyzing phosphodiesters than a mononuclear analogue, Zn(bpta)(OTf)2, where bpta = N,N-bis(2-pyridylmethyl)-tert-butylamine. Hydrolysis of nitrocefin, a beta lactam antibiotic analogue, catalyzed by [Zn2(BPAN)(mu-OH)(mu-O2PPh2)](ClO4)2 involves monodentate coordination of the substrate via its carboxylate group, followed by nucleophilic attack of the zinc(II)-bound terminal hydroxide at the beta-lactam carbonyl carbon atom. Collapse of the tetrahedral intermediate results in product formation. Mononuclear complexes Zn(cyclen)-(NO3)2 and Zn(bpta)(NO3)2, where cyclen = 1,4,7,10-tetraazacyclododecane, are as reactive in the beta-lactam hydrolysis as the dinuclear complex. Kinetic and mechanistic studies of the phosphodiester and beta-lactam hydrolyses indicate that the bridging hydroxide in [Zn2(BPAN)(mu-OH)(mu-O2PPh2)](ClO4)2 is not very reactive, despite its low pKa value. This low reactivity presumably arises from the two factors. First, the briding hydroxide and coordinated substrate in [Zn2(BPAN)(mu OH)(substrate)]2+ are not aligned properly to favor nucleophilic attack. Second, the nucleophilicity of the bridging hydroxide is diminished because it is simultaneously bound to the two zinc(II) ions. PMID- 11196877 TI - Synthesis and characterization of (R-C5H14N2)2[Ga4(C2O4)(H2PO4)2(PO4)4].2H2O, a layered gallium phosphatooxalate containing a chiral amine. AB - The first metal phosphatooxalate containing a chiral amine, (R C5H14N2)2[Ga4(C2O4)(H2PO4)2(PO4)4].2H2O, has been synthesized hydrothermally and characterized by single-crystal X-ray diffraction and 31P MAS NMR spectroscopy. It crystallizes in the monoclinic space group P2(1) (No. 4) with a = 8.0248(4) A, b = 25.955(1) A, c = 9.0127(5) A, beta = 100.151(1) degrees, and Z = 2. The structure consists of GaO6 octahedra and GaO4 tetrahedra connected by coordinating C2O4(2-) and phosphate anions to form anionic sheets in the ac plane with charge-compensating diprotonated R-2-methylpiperazinium cations and water molecules between the layers. There is a good correlation between the NMR spectrum and the structure. PMID- 11196878 TI - An electron paramagnetic resonance study of Mn2(H2O)(OAc)4(tmeda)2 (tmeda = N,N,N',N'-tetramethylethylenediamine): a model for dinuclear manganese enzyme active sites. AB - The complex Mn2(H2O)(OAc)4(tmeda)2 (tmeda = N,N,N',N'-tetramethylethylenediamine) is a model for the active site of hydrolase enzymes containing acetate-bridged dimanganese cores. The two high-spin Mn(II) ions are antiferromagnetically coupled, as determined by previous magnetic susceptibility studies (Yu, S.-B; Lippard, S. J.; Shweky, I; Bino, A. Inorg. Chem. 1992, 31, 3502-3504) to yield a spin "ladder" with total spin S = 0, 1, 2, ..., 5 in increasing energy. In this study, the complex was characterized by Q-band and X-band EPR spectroscopy in frozen solution. Analysis of the temperature dependence of these EPR spectra indicates that the primary spectral contribution is from the S = 2 manifold. The EPR spectra were simulated using a full spin Hamiltonian for this manifold of a coupled spin system, which provided the fit parameters J = -2.9 cm-1, g = 2.00, and D2 = -0.060 +/- 0.003 cm-1. An additional multiline EPR signal is observed which is proposed to arise from the total spin S = 5/2 ground state of a Mn(II) trimer of the type Mn3(OAc)6(tmeda)2. PMID- 11196879 TI - Cation disorder in Ga1212. AB - Substitution of calcium for strontium in LnSr2-xCaxCu2GaO7 (Ln = La, Pr, Nd, Gd, Ho, Er, Tm, and Yb) materials at ambient pressure and 975 degrees C results in complete substitution of calcium for strontium in the lanthanum and praseodymium systems and partial substitution in the other lanthanide systems. The calcium saturation level depends on the size of the Ln cation, and in all cases, a decrease in the lattice parameters with calcium concentration was observed until a common, lower bound, average A-cation size is reached. Site occupancies from X ray and neutron diffraction experiments for LnSr2-xCaxCu2GaO7 (x = 0 and x = 2) confirm that the A-cations distribute between the two blocking-layer sites and the active-layer site based on size. A quantitative link between cation distribution and relative site-specific cation enthalpy for calcium, strontium, and lanthanum within the gallate structure is derived. The cation distribution in other similar materials can potentially be modeled. PMID- 11196880 TI - Cooperative diastereoselectivity of palladium- and platinum-promoted intramolecular [4 + 2] Diels-Alder cycloaddition reactions of 3,4-dimethyl-1 phenylphosphole. AB - The complexes [(DMPP)2M(CH3CN2)]X2 (DMPP = 3,4-dimethyl-1-phenylphosphole; M = Pd, Pt; X = BF4-, NO3-, ClO4-) react with 2 equiv of the dienophiles N,N dimethylacrylamide (DMAA), 2-vinylpyridine (VyPy), and diphenylvinylphosphine (DPVP) to form bis-[4 + 2] Diels-Alder cycloaddition products. The [M(DMPP)2(DMAA)2]2+ and [M(DMPP)2(VyPy)2]2+ complexes form exclusively as the cis geometric isomers, whereas for [M(DMPP)2(DPVP)2]2+, both cis- and trans-geometric isomers are formed. The two Diels-Alder cycloadditions occur sequentially, and the absolute configuration of the first reaction influences the absolute configuration of the second. In all cases, recemic mixtures of the (R,R) and (S,S) diastereomers are formed; none of the meso (R,S) diastereomer is observed. New complexes were characterized by elemental analyses, physical properties, infrared spectroscopy, 1H, 1H(31P), 13C(1H), and 31P(1H) NMR spectroscopy, and, in most cases, X-ray crystallography. PMID- 11196881 TI - Similarities and differences between cobalamins and cobaloximes. Accurate structural determination of methylcobalamin and of LiCl- and KCl-containing cyanocobalamins by synchrotron radiation. AB - The accurate crystal structure determinations of MeCbl (1), CNCbl.2LiCl (2), and CNCbl.KCl (3), based on synchrotron diffraction data collected at 100 K and using high-quality single crystals, are reported. Refinements gave R1 indices of 0.0834 (1), 0.0434 (2), and 0.0773 (3). The influence of the water of crystallization and ion content on the crystal packing of these and other cobalamins (XCbl) is discussed, and a relationship between the crystal packing and the corrin side chain conformations is presented. An analysis of the bond lengths within the corrin moiety, based on 13 accurate structures with several X groups, shows that the trend of the C-C and C-N distances can be interpreted in terms of electronic and steric factors. The variation in structural, NMR and IR spectroscopic, and electrochemical properties are compared with those of cobaloximes, the B12 model, when X is varied. This comparison indicates that the pi-back-donation from metal to the CN axial ligand and the transmission of the trans influence of the X ligand are more effective in cobalamins than in cobaloximes. These findings are consistent with a significantly greater availability of electron charge on Co in cobalamins, and, hence, a semiquantitative evaluation of the electronic difference between the cobalt centers in the two systems is allowed. PMID- 11196882 TI - Linear trichromium complexes with the anion of 2,6-di(phenylimino)piperidine. AB - The anion of 2,6-di(phenylimino)piperidine (DPhIP) has been found to support linear chains of three metal atoms. Three new compounds, [Cr3(DPhIP)4Cl]Cl.(1).5CH2Cl2.0.5H2O (1.1.5CH2Cl2.0.5H2O), [Cr3(DPhIP)4(CH3CN)]- (PF6)2.H2O.4CH3CN (2.H2O.4CH3CN), and [Cr3(DPhIP)4(F)(CH3CN)](BF4)2.5CH3CN (3.5CH3CN), have been synthesized and characterized by X-ray crystallography. Compound 1 has a linear chain of three chromium atoms arranged in an unsymmetrical fashion, with two of them forming a quadruply bonded unit (Cr-Cr distance 1.932(2) A) and the third being a non-metal-metal-bound 5-coordinate unit (Cr...Cr distance 2.659(2) A). The fifth coordination site is occupied by a chloride ion, and another chloride ion is located in the interstices of the crystal. The trimetal unit in compound 2 is structurally similar to that in compound 1 except that the axial ligand in 2 is a CH3CN molecule. Compound 3 is an oxidation product prepared by reaction of 1 with AgBF4. Here, a square pyramidal CrIII unit, FCrN4, and a Cr-Cr quadruply bonded (Cr-Cr distance 1.968(2) A) unit, with an axially coordinated acetonitrile molecule, form the trichromium chain. The CrIII...CrII separation of 2.594(2) A in 3 is too long to be considered a bonding interaction. PMID- 11196883 TI - Straightforward conversion route to nanocrystalline monothiooxides of rare earths through a high-temperature colloid technique. PMID- 11196884 TI - Synthesis of arene-soluble dizirconium nonaisopropoxide lanthanide cations involving divalent ytterbium. PMID- 11196885 TI - Synthesis, characterization, and properties of a lithium 21-thiaporphyrin complex. PMID- 11196886 TI - On the failure to observe isotropic electron paramagnetic resonance spectra for certain chromium(I) carbonyl complexes. PMID- 11196887 TI - XAS investigation of the nickel active site structure in Escherichia coli glyoxalase I. PMID- 11196888 TI - Elemental solvothermal reaction to produce ternary semiconductor CuInE2 (E = S, Se) nanorods. PMID- 11196889 TI - Strong differences in the in vitro cytotoxicity of three isomeric dichlorobis(2 phenylazopyridine)ruthenium(II) complexes. PMID- 11196890 TI - Involvement of multiply bonded dirhenium complexes in mixed-metal assemblies. Isolation and characterization of a new type of Re4Pd2 cluster. PMID- 11196891 TI - Synthesis and structural characterization of quaternary thorium selenophosphates: A2ThP3Se9 (A = K, Rb) and Cs4Th2P5Se17. AB - Single crystals of A2ThP3Se9 (A = K (I), Rb (II)) and Cs4Th2PsSe17 (III) form from the reaction of Th and P in a molten A2Se3/Se (A = K, Rb, Cs) flux at 750 degrees C for 100 h. Compound I crystallizes in the triclinic space group P1 (No. 2) with unit cell parameters a = 10.4582(5) A, b = 16.5384(8) A, c = 10.2245(5) A, alpha = 107.637(1); beta = 91.652(1); gamma = 90.343(1) degrees, and Z = 2. Compound II crystallizes in the triclinic space group P1 (No. 2) with the unit cell parameters a = 10.5369(5) A, b = 16.6914(8) A, c = 10.2864(5) A, alpha = 107.614(1) degrees, beta = 92.059(1) degrees, gamma = 90.409(1) degrees, and Z = 2. These structures consist of infinite chains of corner-sharing [Th2Se14] units linked by (P2Se6)4- anions in two directions to form a ribbonlike structure along the [100] direction. Compounds I and II are isostructural with the previously reported K2UP3Se9. Compound III crystallizes in the monoclinic space group P2(1)/c (No. 14) with unit cell parameters a = 10.238(1) A, b = 32.182(2) A, c = 10.749(1) A; beta = 95.832(1) degrees, and Z = 4. Cs4Th2P5Se17 consists of infinite chains of corner-sharing, polyhedral [Th2Se13] units that are also linked by (P2Se6)4- anions in the [100] and [010] directions to form a layered structure. The structure of III features an (Se2)2- anion that is bound eta 2 to Th(2) and eta 1 to Th(1). This anion influences the coordination sphere of the 9 coordinate Th(2) atom such that it is best described as bicapped trigonal prismatic where the eta 2-bound anion occupies one coordination site. The composition of III may be formulated as Cs4Th2(P2Se6)5/2(Se2) due to the presence of the (Se2)2- unit. Raman spectra for these compounds and their interpretation are reported. PMID- 11196892 TI - Model investigations of vanadium-protein interactions: novel vanadium(III) and oxovanadium(IV) compounds with the diamidate ligand 1,2-bis(2 pyridinecarboxamide)benzene (H2bpb). AB - Novel vanadium(III) and oxovanadium(IV) compounds with the diamidate ligand 1,2 bis(2-pyridinecarboxamide)benzene (H2bpb) were synthesized and structurally characterized. H2bpb is capable of binding to vanadium in either its anionic (dianionic-monoanionic) or its neutral form, resulting in complexes of various geometries and stoichiometries. The dianionic form (bpb2-), in NHEt3(trans [VCl2(bpb)]) (1) and [VO(bpb)(H2O)]05dmso036CH3OH013H2O (6x05dmsox036CH3OHx013H2O), acts as a planar tetradentate bis[N-amidate-N pyridine] equatorial ligand. The monoanionic form (Hbpb-) behaves as an (Npy,Oam) or (Npy,Nam) chelator in [V(Hbpb)3]2CHCl3 (22CHCl3) as well as a mu 2-bridging eta 4-(Npy,Oam-Npy,Nam) in [VOCl(Hbpb)](2)x2CH3NO2 (3x2CH3NO2), while the neutral H2bpb behaves as a mu 2-bridging-eta 4-bis(Npy,Oam) in [VOCl(H2bpb)](2)x104CH3OHx123thfx074H2O (4x104CH3OH123thf074H2O). Compound 4x104CH3OHx123thfx074H2O crystallizes in the triclinic system P1, with (at 25 degrees C) a = 9140(2) A, b = 11058(2) A, c = 14175(2) A, alpha = 99013(5) degrees, beta = 104728(7) degrees, gamma = 102992(7) degrees, V = 13149(4) A3, Z = 1, while compound 605dmso036CH3OH013H2O crystallizes in the monoclinic space group P2(1)/n with (at 25 degrees C) a = 11054(5) A, b = 11407(5) A, c = 16964(7) A, beta = 932(1) degrees, V = 2136(2) A3, Z = 4. Variable temperature magnetic susceptibility studies of the dimeric compounds 3x2CH3NO2 and 4x104CH3OH show g values for the V(IV) centers that are slightly smaller than 20 (as expected for d1 ions) and indicate small antiferromagnetic coupling between the two vanadium(IV) centers. Ab initio calculations were also carried out, providing results concerning the effect of the relative strength and the deformation energy involved in the eta 2-(Npy,Nam) and eta 2-(Npy,Oam) bonding modes in the ligation of Hbpb- to vanadium. PMID- 11196893 TI - A systematic evaluation of molecular recognition phenomena. 1. Interaction between phosphates and nucleotides with hexaazamacrocyclic ligands containing m xylylic spacers. AB - The host-guest interactions between ortho- (Ph), pyro- (Pp), and tripolyphosphate (Tr) anions together with ATP (At), ADP (Ad), and AMP (Am) nucleotides and the hexaazamacrocyclic ligand 3,7,11,19,23,27-hexaazatricyclo[27311(13,17)]triaconta- 1(32),13,15,17(34),29(33),30-hexaene (Bn) have been investigated by potentiometric equilibrium methods. Ternary complexes are formed in aqueous solution as a result of hydrogen bond formation and Coulombic attraction between the host and the guest. Formation constants for all the species obtained are reported. The selectivity of the Bn ligand with regard to the phosphate and nucleotide substrates is discussed and illustrated with species distribution diagrams. A comparison of the present results with those obtained for the similar but smaller macrocyclic ligand 3,6,9,17,20,23- hexaazatricyclo[23311(11,15)]triaconta-1(29),11(30),12,14,25,27-hexaene (Bd) is also discussed. It is found that the competition of the Bd and Bn ligands for the formation of ternary species with a specific substrate is strongly dependent on the p[H]. The crystal structure of the compound [(H6Bn)(H2PO4)6]2H2O with empirical formula C28H68N6O26P6 has been solved by means of X-ray diffraction analysis. The compound belongs to the triclinic P1 space group with Z = 1, a = 8892(2) A, b = 9369(4) A, c = 16337(8) A, alpha = 7372(4) degrees, beta = 8301(4) degrees, and gamma = 6481(3) degrees. The phosphate counterions are found to bridge adjacent layers of macrocyclic molecules through an extensive hydrogen bonding network PMID- 11196894 TI - A systematic evaluation of molecular recognition phenomena. 2. Interaction between phosphates and nucleotides with hexaazamacrocyclic ligands containing diethylic ether spacers. AB - The host-guest interactions between ortho- (Ph), pyro- (Pp), and tripolyphosphate (Tr) anions together with ATP (At), ADP (Ad), and AMP (Am) nucleotides and the two hexaazamacrocyclic ligands 1,15-dioxa-4,8,12,18,22,26-hexaazacyclooctacosane (Pn) and 1,13-dioxa-4,7,10,16,20,24-hexaazacyclohexacosane (Op) have been investigated by potentiometric equilibrium methods. Ternary complexes are formed in aqueous solution as a result of hydrogen bond formation and Coulombic attraction between the host and the guest. Formation constants for all the species obtained are reported. The selectivity of the Pn and Op ligands with regard to the different phosphate and nucleotide substrates is discussed and illustrated with total species distribution diagrams. A comparison is also carried out, with the results obtained in this work and those obtained previously with three other closely related hexaazamacrocyclic ligands. This comparison manifests the importance of ligand basicity, rigidity, and pi-stacking capability in order to understand their binding and selectivity. PMID- 11196895 TI - "Bridging hydroxide effect" on mu-carboxylato coordination and electrochemical potentials of bimetallic centers: Mn2(II,II) and Mn2(III,III) complexes as functional models of dimanganese catalases. AB - Synthesis, solution structures, and electrochemistry of several dinuclear Mn2(II,II) complexes (1-4) and Mn2(III,III) complexes (6 and 8), derived from a functional catalase mimic [(L1,2)Mn2(II,II)(mu 13-O2CCH3)]2+ (1) are described that enable testing of the role of intramolecular hydroxide ligands on the redox properties. Addition of 1 equiv of hydroxide to 1 or 3 forms [(L1,2)Mn2(II,II)(mu 13-O2CCH3)(mu- OH)]+ (7A or 7B, respectively), possessing two six-coordinate Mn(II) ions bridged by hydroxide and acetato ligands. Two-electron oxidation of 7 with O2 occurs by forming [(L1,2)Mn2(III,III)(mu 1,3-O2CCH3)(mu-OH)]3+ (8) and H2O2 with no ligand rearrangements in methanol. Reaction of 8 with 2-3 equiv hydroxide forms [(L1,2)Mn2(III,III)(mu-O)(OH)(O2CCH3)]+ in which deprotonation of mu-OH- to yield mu-O2- favors subsequent addition of a terminal hydroxide ligand, accommodated by a bridging-to-terminal "carboxylate-shift". Preservation of six coordinate Mn(II) ions throughout all hydroxide-induced transformations is observed, including oxidation by O2. Cyclic voltammetry reveals that addition of mu-OH- converts the two-electron redox couple II,II/III,III for complexes 1-4 to sequential one-electron couples at lower reduction potentials, yielding substantial stabilization of the II,III and III,III oxidation states by delta E = 440 and 730 mV, respectively. Binding of a second OH- to 7A or 7B forms (L1,2)Mn2(II,II)(mu 13-O2CCH3)(OH)2, containing two six-coordinate Mn(II) ions with two terminal hydroxides and a mu 1,3-bridging acetato. Electrochemistry reveals that displacement of the bridging hydroxide to a terminal site upon addition of the second OH- restores a two-electron redox couple II,II/III,III but now at a higher reduction potential with considerable loss of the electrochemical stabilization energy provided by the mu-OH- (delta E = 250 and 350 mV loss for Mn2(II,II) and Mn2(III,III), (respectively). These results indicate a considerably stronger influence of bridging vs terminal hydroxide ligands in stabilizing the higher oxidation states and separating the one-electron redox potentials of bimetallic centers. By contrast, in the absence of mu-OH- bridges the longer separation with the mu 1,3-carboxylato bridge in dimanganese(II,II) complexes leads to nearly complete uncoupling of the Mn(II) oxidation potentials, thus yielding a two-electron redox transition to (III,III). We hypothesize that this "bridging hydroxide effect" may be due to both greater screening of the repulsive intermetallic electric potential energy and increased resonance stabilization of the mixed-valence (II,III) oxidation state by charge delocalization . These data provide a physicochemical basis for interpretation of the catalase activity of these complexes and of dimanganese catalase enzymes (see the following manuscript). PMID- 11196896 TI - Mechanism of hydrogen peroxide dismutation by a dimanganese catalase mimic: dominant role of an intramolecular base on substrate binding affinity and rate acceleration. AB - Several modifications of the manganese coordination environment and oxidation states of a family of synthetic dimanganese complexes have been introduced in search of the structural features that promote high rates of hydrogen peroxide dismutation (catalase activity). The X-ray structure of reduced catalase (T thermophilus) reveals a dimanganese(II,II) site linked by three bridges: mu 13 glutamate-, mu-OH-, and mu-OH2. The roles of a bridging hydroxide vs mu-aqua and the carboxylate have been examined in the reduced Mn2(II,II) complexes, [(L1,2)Mn2(mu-O2CCH3)(mu-X)]2+ for X- = OH- (7A) or X = H2O (1-4), and their oxidized Mn2(III,III) analogues, [(L1,2)Mn2(mu-O)(O2CCH3)(OH)]+ (6) (L1 is N,N,N',N'-tetrakis(2-methylenebenzamidazolyl)-1,3-diaminopropan- 2-ol, and L2 is the tetrakis-N-ethylated analogue of L1, which has all amine protons replaced by ethyl groups). The steady-state catalase rate is first-order in concentration of both substrate and reduced catalyst and saturates at high peroxide concentrations in all cases, confirming peroxide/catalyst complex formation. No catalyst decomposition is seen after > 2000 turnovers. Catalysis proceeds via a ping-pong mechanism between the Mn2(II,II/III,III) redox states, involving complexes 6 and 7A/7A'. The Mn2(III,IV) oxidation state was not active in catalase activity. Replacement of the mu-aqua bridge by mu-hydroxide eliminates a kinetic lag phase in production of the O2 product, increases the affinity for substrate peroxide in the rate-limiting step as seen by a 5-fold. decrease in the Michaelis constant (KM), and accelerates the maximum rate (kcat) by 65-fold The kinetic and spectroscopic data are consistent with substrate deprotonation by the hydroxide bridge, yielding a hydroperoxyl bridge coordinated between the Mn ions (mu, eta 2 geometry, "end-on") as the basis for catalysis: mu-OH- + H2O2-->mu-O2H- + H2O. Binding of a second hydroxide ion to 7A causes a further increase in kcat by 4 fold with no further change in substrate affinity (KM). By contrast, free (noncoordinating) bases in solution have no effect on catalysis, thus establishing intramolecular sites for both functional hydroxide anions. Solution structural studies indicate that the presence of 2-5 equiv of hydroxide in solution leads to formation of a bishydroxide species, [(L1,2)Mn2(mu 13 O2CCH3)(OH)2], which in the presence of air or oxygen auto-oxidizes to yield complex 6, a Mn2(III,III)(mu-O) species. Complex 6 oxidizes H2O2 to O2 without a kinetic lag phase and is implicated as the active form of the oxidized catalyst. A maximum increase by 240-fold in catalytic efficiency (kcat/KM = 700 s-1 M-1) is observed with the bishydroxide species versus the aquo complex 1, or only 800 fold less efficient than the enzyme. Deprotonation of the amine groups of the chelate ligand L was shown not to be involved in the hydroxide effects because identical results were obtained using the catalyst with tetrakis(N-ethylated)-L. Uncoupling of the Mn(II) spins by protonation of the alkoxyl bridge (LH) was observed to lower the catalase activity. Comparisons to other dimanganese complexes reveals that the Mn2(II,II)/Mn2(III,III) redox potential is not the determining factor in the catalase rate of these complexes. Rather, rate acceleration correlates with the availability of an intramolecular hydroxide for substrate deprotonation and with binding of the substrate at the bridging site between Mn ions in the reductive O-O bond cleavage step that forms water and complex 6. PMID- 11196897 TI - Binding of pi-acceptor ligands to (triamine)iron(II) complexes. AB - A series of (Me3TACN)FeII derivatives with soft coligands have been investigated, where Me3TACN is N,N',N"-trimethyl-1,4,7-triazacyclononane. Treatment of Me3TACN with FeCl2 afforded a compound with the empirical formula (Me3TACN)FeCl2 (1). Compound 1, which is a versatile precursor reagent, was shown by single-crystal X ray diffraction to be the salt [(Me3TACN)2Fe2Cl3][(Me3TACN)FeCl3], containing isolated [(Me3TACN)2Fe2Cl3]+ and [(Me3TACN)FeCl3]- subunits. Treatment of 1 with NaBPh4 gave the known [(Me3TACN)2Fe2Cl3]BPh4, while the addition of Me3TACN to FeCl4(2-) gave [(Me3TACN)FeCl3]-. Oxygenation of 1 afforded [(Me3TACN)FeCl2]2(mu O), which was shown crystallographically to be centrosymmetric with a pair of distorted octahedral Fe centers. The Fe-N bond trans to the Fe-O bond is elongated by 02 A relative to the other Fe-N distances. Solutions of 1 and thiolates absorb CO to give [(Me3TACN)Fe(SPh)(CO)2]BPh4 and (Me3TACN)Fe(S2C2H4)(CO) (nu CO = 1896 cm-1). Treatment of 1 with excess CN- afforded [(Me3TACN)Fe(CN)3]-, isolated as its PPh4+ salt 5. Crystallographic and spectroscopic studies show that 5 is low spin with a C3v structure; its Fe-N distances contracted by 023 A relative to those in [(Me3TACN)FeCl3]-. Aqueous solutions of 1 bind CO upon the addition of CN- to produce (Me3TACN)Fe(CN)2(CO) (6) Analogous to 6 is (Me3TACN)Fe(CN)2(CNMe), prepared by methylation of 5. The metastable dicarbonyl [(Me3TACN)FeI(CO)2]I was prepared by treatment of FeI2(CO)4 with Me3TACN and was crystallographically characterized as its BPh4- salt. Values of E1/2 for [(Me3TACN)FeCl3]-, 5, and 6 are -0409, -0640, and 0533 V vs Fc/Fc+, respectively. PMID- 11196898 TI - Syntheses and structures of heterobicyclic bis(tert butylamido)cyclodiphosph(III)azane compounds having phosphorus(III) and arsenic(III) centers. AB - Syntheses and single-crystal X-ray diffraction studies of heterobicyclic cyclodiphosphazanes having central phosphorus(III) and arsenic(III) atoms are described. Interaction of PCl3 or AsCl3 with cis-[(tBuNP)2(tBuNLixTHF)2] produced the isomorphous ([(tBuNP)2(tBuN)2]ECl); E = P(1), As(4), respectively. These Cs symmetric molecules crystallize with two molecules in the monoclinic space group P2(1)/m. Unit cell dimensions of 1 are (293 K) a = 9.777(1) A, b = 11.745(1) A, c = 9.986(2) A, and beta = 97.44(1) degrees; those of 4 are (213 K) a = 9.688(3) A, b = 11.873(3) A, c = 9.975(3) A, and beta = 97.80(3) degrees. When ([(tBuNP)2(tBuN)2]PCl) was treated with NaN3 or LiN(SiMe3)2, ([(tBuNP)2(tBuN)2]PN3)(2) and ([(tBuNP)2(tBuN)2]PN(SiMe3)2)(3), respectively, were obtained. Compound 2 crystallizes in the monoclinic space group P2(1)/m and has until-cell dimensions (213 K) of a = 9496(7) A, b = 12455(7) A, c = 10043(6) A, and beta = 9723(4) degrees, Z = 2. PMID- 11196899 TI - Structurally diverse copper(II)-carboxylato complexes: neutral and ionic mononuclear structures and a novel binuclear structure. AB - The copper complexes with the commercial auxin herbicides MCPA, 2,4-D, and 2,4,5 T in the presence of a nitrogen donor heterocyclic ligand, phen or bipyam, were prepared and characterized. The available evidence supports a dimeric structure for the 2,4-D complex in the presence of bipyam while phen leads to monomeric forms. The EPR spectrum of Cu2(2,4-D)4(bipyam)2 at 4 K in the solid state exhibits an axial signal which corresponds to almost isolated S = 1/2 magnetic ions. Magnetic data for the dimer show a weak antiferromagnetic interaction between the two metal ions with J = -08 cm-1. The crystal structures of tetrakis[(2,4-dichlorophenoxy)acetato]bis(2,2'-bipyridylamine)dicopper(II), 1, bis(1,10-phenanthroline)[(2,4,5-trichlorophenoxy)acetato]copper(II) chloride, 2, and aqua(1,10-phenanthroline)bis[((2-methyl-4-chlorophenoxyacetato]copper(II), 3, were determined and refined by least-squares methods using three-dimensional MoK alpha data. 1 crystallizes in space group P1, in a cell of dimensions a = 10813(1) A, b = 12138(1) A, c = 11909(1) A, alpha = 86448(3) degrees, beta = 80127(3) degrees, and gamma = 63982(3) degrees, and V = 13837(2) A3, with Z = 1 2 crystallizes in space group I2/a, in a cell of dimensions a = 29958(9) A, b = 11342(3) A, c = 21196(7) A, beta = 10794(1) degrees, and V = 68522(4) A3, with Z = 8 3 crystallizes in space group P1, in a cell of dimensions a = 87419(8) A, b = 12512(1) A, c = 14598(1) A, alpha = 110737(1) degrees, beta = 95742(2) degrees, gamma = 103286(2) degrees, V = 14241(2) A3, with Z = 2. PMID- 11196900 TI - Supramolecular complex of cytochrome c with lariat ether: solubilization, redox behavior and catalytic activity of cytochrome c in methanol. AB - A variety of lariat ethers were employed to solubilize water-soluble cytochrome c in methanol, in which alcohol, ether, ester, amine, and amide functionalities were attached as cation-ligating side arms to 18-crown-6, 15-crown-5, and 12 crown-4 rings. Among these lariat ethers, the alcohol-armed 18-crown-6 derivative offered the highest solubilization efficiency for cytochrome c via supramolecular complexation. The resulting cytochrome c-lariat ether complexes were electrochemically and spectroscopically characterized and confirmed to have redox active heme structures of 6-coordinate low-spin population in methanol. Some of them catalyzed the oxidation of pinacyanol chloride with hydrogen peroxide in methanol and exhibited higher activities than unmodified cytochrome c and its poly(ethylene glycolated) derivative. Since the supramolecular complexation between lariat ether and cytochrome c includes extremely simple procedures, it provides a facile preparation method of effective biocatalysts working in organic solvents from metalloproteins. PMID- 11196901 TI - Isothermal titration calorimetry measurements of Ni(II) and Cu(II) binding to His, GlyGlyHis, HisGlyHis, and bovine serum albumin: a critical evaluation. AB - The binding of Ni(II) and Cu(II) to histidine, to the tripeptides GlyGlyHis and HisGlyHis, and to the protein bovine serum albumin has been studied by isothermal titration calorimetry (ITC) to determine the experimental conditions and data analysis necessary to reproduce literature values for the binding constants and thermodynamic parameters. From analysis of the ITC data, we find that there are two major considerations for the use of this method to accurately quantify metal ion interaction with biological macromolecules. First, to determine true pH independent binding constants, ITC data must be corrected for metal ion competition with protons by accounting for the experimental pH and pKa values of the metal-binding residues. Second, metal interaction with the buffer (stability and enthalpy of formation of metal-buffer complex(es)) must be included in the analysis of the ITC data to determine the binding constants and the change in enthalpy. While it may be possible to use a buffer that forms only weak, and therefore negligible, complexes with the metal, a buffer that has a strong and well-characterized interaction has the benefit of suppressing metal ion hydrolysis and precipitation, and of allowing the quantification of high-affinity metal-binding sites on biological macromolecules. This study has also quantified the contribution of the N-terminal imidazole of HisGlyHis to the stability of the Cu(II) and Ni(II) complexes of this protein sequence and has provided new insight about Cu(II) binding to albumin. PMID- 11196902 TI - New linear tricobalt complex of di(2-pyridyl)amide (dpa), [Co3(dpa)4(CH3CN)2][PF6]2. AB - Reaction of the linear tricobalt compound Co3(dpa)4Cl2 (1) (dpa = di(2 pyridyl)amide) with silver hexafluorophosphate in acetonitrile yields [Co3(dpa)4(CH3CN)2][PF6]2 (2). Two crystalline forms are obtained from the same solution, namely, a monoclinic (P2(1)) form 2xCH3CNx2Et2O and a triclinic (P1) form, 2x3CH3CN. The tricobalt units in both crystals are essentially symmetrical, though this is not required by crystal symmetry, with Co-Co distances in the range 2298-2304 A. Each of the two terminal Co atoms is coordinated to an acetonitrile molecule with Co-N distances in the range 2068-2111 A at 213 K. The spiral arrangement of ligands gives an overall idealized D4 point group symmetry for the cation [Co3(dpa)4(CH3CN)2]2+ . Chiral crystals of both delta and lambda configurations in the P2(1) form have been isolated. The absolute configurations were determined by X-ray crystallography and their mirror-image circular dichroism spectra measured. The D4 symmetry of the cation appears to be preserved in solution as judged by the presence of only five proton resonance signals in the 1H NMR spectrum. Magnetic susceptibility measurements in the solid state indicates that 2 has a doublet ground state and exhibits an increase of the effective moment at high temperature (approximately 160 K) due to a spin crossover process. PMID- 11196903 TI - Synthesis, structure, and multi-NMR studies of (Me4N)[A(M(SC(O)Ph)3)2] (A = Na, M = Hg; A = K, M = Cd or Hg). AB - The compounds (Me4N)[A(M(SC(O)Ph)3)2] (A = K, M = Cd (2); A = Na, M = Hg (3); and A = K, M = Hg (4)) were synthesized by reacting the appropriate metal chloride with A+PhC(O)S- and Me4NCl in the ratios 1:3:1 and 2:6:1. The structures of these compounds were determined by single-crystal X-ray diffraction methods. All the compounds are isomorphous, isostructural, and crystallized in the space group P1 with Z = 1. Single-crystal data for 2: a = 106670(2) A, b = 111522(2) A, c = 119294(2) A, alpha = 71782(1) degrees, beta = 85208(1) degrees, gamma = 69418(1) degrees, V = 126140(4) A3, Dcalc = 1528 g cm-3. Single-crystal data for 3: a = 10840(2) A, b = 10946(4) A, c = 12006(3) A, alpha = 7218(2) degrees, beta = 8675(2) degrees, gamma = 6743(2) degrees, V = 12493(6) A3, Dcalc = 1756 g cm-3. Single-crystal data for 4: a = 104780(1) A, b = 112563(2) A, c = 119827(2) A, alpha = 71574(1) degrees, beta = 85084(1) degrees, gamma = 70705(1) degrees, V = 126523(3) A3, Dcalc = 1755 g cm-3. In the [A(M(SC(O)Ph)3)2]- anions, each M(II) atom is bonded to three thiobenzoate ligands through sulfur atoms, giving a trigonal planar MS3 geometry. The carbonyl oxygen atoms from the two [M(SC(O)Ph)3]- anions are bonded to the alkali metal atom, providing an octahedral environment. Solution metal NMR studies showed the concentration dependent dissociation of the alkali metal ions in the trinuclear anions. PMID- 11196904 TI - Mechanism and molecular-electronic structure correlations in a novel series of osmium(V) hydrazido complexes. AB - Reaction between the Os(VI) nitrido (OsVI identical to N+) complexes [OsVI(L3)(Cl)2(N)]+ (L3 is 2,2':6',2"-terpyridine (tpy) or tris(1 pyrazolyl)methane (tpm)) and secondary amines (HN(CH2)4O = morpholine, HN(CH2)4CH2 = piperidine, and HN(C2H5)2 = diethylamine) gives Os(V)-hydrazido complexes, [OsV(L3)(Cl)2(NNR2)]+ (NR2 = morpholide, piperidide, or diethylamide). They can be chemically or electrochemically oxidized to Os(VI) or reduced to Os(IV) and Os(III). The Os-N bond lengths and Os-N-N angles in the structures of these complexes are used to rationalize the bonding between the dianionic hydrazido ligand and Os. The rate law for formation of the Os(V) hydrazido complexes with morpholine as the base is first order in [OsVI(L3)(Cl)2(N)]+ and second order in HN(CH2)4O with ktpy(25 degrees C, CH3CN) = (581 +/- 12) M-2 s-1 and ktpm(25 degrees C, CH3CN) = 2683 +/- 40 M-2 s-1. The proposed mechanism involves initial nucleophilic attack of the secondary amine on the Os(VI) nitrido group to give a protonated Os(IV)-hydrazido intermediate. It is subsequently deprotonated and then oxidized by OsVI identical to N+ to Os(V). The extensive redox chemistry for these complexes can be explained by invoking a generalized bonding model. It can also be used to assign absorption bands that appear in the electronic from the visible-near-infrared spectra including a series of d pi-->d pi interconfigurational bands at low energy. PMID- 11196905 TI - Synthesis, structure, and bonding of A5Cd2Tl11, A = Cs, Rb. Naked pentagonal antiprismatic columns centered by cadmium. AB - A new anionic thallium cluster chain 1 infinity[Cd2Tl11(5-)] has been discovered in the A-Cd-Tl systems for A = Cs, Rb. The compounds are synthesized by direct fusion of the elements at 700 degrees C and equilibration of the quenched product at 200 degrees C for 1 month. The thallides crystallize in the orthorhombic space group Amm2, Z = 2, a = 56107(7) and 55999(6) A, b = 18090(3) and 17603(3) A, c = 13203(3) and 12896(2) A for A = Cs and Rb, respectively, and contain chains of face-sharing pentagonal Tl10 antiprisms embedded in a matrix of alkali metal cations. Cadmium atoms occupy the center of the antiprisms and donate electrons to the anionic chain. Additional four-bonded Tl atoms on one side of the chain make the structure acentric. The compounds are diamagnetic (chi 296 = -08, -40 (x 10(-4) emu/mol, respectively) and metallic (10-20 mu omega cm at 275 K), and the indirect band gap energy of both compounds is close to zero according to extended Huckel calculations on the isolated chain. PMID- 11196906 TI - Synthesis and structures of new ternary aluminum chalcogenides: LiAlSe2, alpha LiAlTe2, and beta-LiAlTe2. AB - The synthesis and crystal structures of new ternary aluminum chalcogenides, LiAlSe2, alpha-LiAlTe2, and beta-LiAlTe2, are reported. These compounds are synthesized by solid-state reaction at 800 degrees C. The single-crystal X-ray structures of these compounds have been determined. LiAlSe2: a = 68228(9) A, b = 8266(1) A, c = 65236(7) A, Pna2(1) (No 33, Z = 4) alpha-LiAlTe2: a = 65317(4) A, c = 116904(9) A, I42d (No 122, Z = 4) beta-LiAlTe2: a = 44810(6) A, c = 7096(1) A, P3m1 (No 156, Z = 1). These ternary compounds are formed by fusion of AlQ4 (Q = Se, Te) tetrahedra. LiAlSe2 shows beta-NaFeO2 structure type, which can be viewed as a wurtzite superstructure. alpha-LiAlTe2 adopts chalcopyrite structure type. In LiAlSe2 and alpha-LiAlTe2, AlQ4 (Q = Se, Te) tetrahedra share four corners to build three-dimensional structures and Li atoms are located in the tetrahedral sites between the chalcogen layers. beta-LiAlTe2 has polar layers formed by three-corner shared AlTe4 tetrahedra, and Li cations are in the distorted antiprisms between the layers. 7Li MAS NMR studies show that chemical shifts of Li in these ternary chalcogenides are nearly identical regardless of different chemical environments. PMID- 11196907 TI - Time-resolved infrared spectroscopic study of reactive acyl intermediates relevant to cobalt-catalyzed carbonylations. AB - Time-resolved infrared spectroscopic studies have been used to characterize the reactive intermediate CH3C(O)Co(CO)2PPh3 (ICo), which is relevant to the mechanism of the catalysis of alkene hydroformylation by the phosphine-modified cobalt carbonyls. Step-scan FTIR and (variable) single-frequency time-resolved infrared detection on the microsecond time scale were used to record the spectrum of ICo and to demonstrate that the principal photoproduct of the subsequent reaction of this species at PCO = 1 atm is the methyl cobalt complex CH3Co(CO)3PPh3 (MCo). At higher PCO the trapping of ICo with CO to re-form CH3C(O)Co(CO)3PPh3 (ACo) (rate = kCO[CO][ICo]) was shown to become competitive with the rate of acetyl-to-cobalt methyl migration to give MCo (rate = kM[ICo]). Activation parameters for the competing pathways in benzene were determined to be delta H++CO = 57 +/- 04 kJ mol-1, delta S++CO = -91 +/- 12 J mol-1 K-1 and delta H++M = 40 +/- 2 kJ mol-1, delta S++M = -19 +/- 5 J mol-1 K-1. The effects of varying the solvent on the competitive reactions of ICo were also explored, and the mechanistic implications of these results are discussed. PMID- 11196908 TI - Time-resolved IR studies of [Re(LL)(CO)4]+. PMID- 11196909 TI - Monodentate-bridged phosphodiester and sulfate complexes: structural insights into the biological activation of phosphodiesters, sulfate, and sulfate esters. PMID- 11196910 TI - Varying coordination modes and magnetic properties of copper(II) complexes with diazamesocyclic ligands by altering additional donor pendants on 1,5 diazacyclooctane. AB - A series of new diazamesocyclic ligands based on a diazamesocycle, 1,5 diazacyclooctane (DACO), functionalized by additional donor groups--1,5-bis(N-1 methylimidazol-2-ylmethyl)-1,5- diazacyclooctane (L1), 1-(2-hydroxybenzyl)-1,5 diazacyclooctane (HL2), 1,5-bis(2-hydroxybenzyl)-1,5-diazacyclooctane (H2L3), and 1-(N-1-methylimidazol-2-ylmethyl)-1,5-diazacyclooctane (L4)--and their Cu(II) complexes have been synthesized and characterized. Single-crystal X-ray diffraction analysis of the four Cu(II) complexes revealed that L1 forms a five coordinate mononuclear complex, HL2 a N3- mu-bridged binuclear complex, H2L3 an oxygen mu-bridged trinuclear complex, and L4 a one-dimensional zigzag coordination polymeric complex with Cu(II). [CuL1ClO4](ClO4) (I): a = 12.194(2) A, b = 13.351(3) A, c = 14.473(3) A, beta = 107.10(3) degrees, Z = 4. [CuL2(N3)]2 (II): a = 8.1864(6) A, b = 18.141(2) A, c = 9.3307(7) A, beta = 103.662(6) degrees, Z = 2. [Cu3(L3)2Cl2] (III): a = 10.7296(13) A, b = 13.7707(17) A, c = 13.5523(17) A, beta = 106.350(3) degrees, Z = 2. ([CuL4Cl]2ClO4) infinity (IV): a = 7.279(1) A, b = 23.695(5) A, c = 19.308(4) A, beta = 100.28(3) degrees, Z = 8. All four complexes crystallize in the monoclinic crystal system with the P2(1)/c space group, and each Cu(II) center coordinated with DACO is pentacoordinated with a distorted square-pyramidal or trigonal-bipyrimidal coordination environment. In complex IV, the binuclear cation unit [CuL4Cl]2(2+) constitutes the fundamental building block of an infinite alternating zigzag chain structure, and the binuclear unit contains two types of geometries around the Cu(II) centers: the Cu(1) center is a distorted square-pyramidal environment, while the Cu(2) is a distorted trigonal-bipyramidal coordination environment. To the best of our knowledge, this is the first Cu(II) complex of a diazamesocyclic ligand with an infinite polymeric structure. The magnetic properties of complexes II, III, and IV have been investigated by variable-temperature magnetic susceptibility measurements in the solid state. The obtained parameters are 2J = 2.06 cm-1 (II), -345.56 cm-1 (III), and -2.60 cm-1 (IV), which differ greatly from ferromagnetic to weak and strong antiferromagnetic coupling. These results unequivocally indicate that the nature of the pendant arms is a key factor governing the structure and properties of the complexes; therefore, the coordination modes and properties of the metal complexes of a diazamesocycle can be controlled by altering the pendant donors on it. Magneto-structural correlation has been precisely analyzed, and the solution properties of these complexes have also been described. PMID- 11196911 TI - Electronic structures of M21S8 (M = Nb, Zr) and (M,M')21S8 (M, M' = Hf, Ti; Nb, Ta) phases and reasons for variations in the metal site occupations. AB - The electronic structures of binary M21S8 (M = Nb, Zr) and isostructural ternary (M,M')21S8 (M, M' = Hf, Ti; Nb, Ta) phases have been studied by means of extended Huckel tight-binding band structure calculations. For the valence electron concentration in the binary group 5 metal phase Nb21S8, metal-metal bonding is optimized whereas, in the isostructural group 4 metal phase Zr21S8, metal-metal bonding levels exist above the Fermi level. However, the electronic structure analysis suggests a stable structure for M21S8 phases with group 4 metals and that (M,M')21S8 phases with mixed group 4 and group 5 metals, even if not yet reported, could well exist. In the ternary phase Nb6.9Ta14.1S8, a linear relationship exists between the magnitude of the metal-metal bonding capacity (as expressed by the total metal-metal Mulliken overlap population) of each crystallographically independent metal site and the occupation of the site with the heavier metal (i.e., the element with the greater bonding capability). The situation is quite more complex in Hf7.5Ti13.5S8, where the metal-metal bonding capacity of each site, differences in electronegativity between Ti and Hf, and site volume arguments must be taken into account to understand the metal site occupation. PMID- 11196912 TI - Ab initio study of rearrangements on the (CH)2(BR)2, R=H, and NH2 potential energy surfaces. AB - A comprehensive survey of the (CH)2(BH)2 potential energy surface was carried out at the [MP4/6-311 + G(d,p)]//MP2/6-31G(d) level. Many of the classical and nonclassical isomers of the carborane surface are separated by high activation barriers, which explains why derivatives of most isomers could be prepared as stable compounds at room temperature. The transition states are grouped into two types, hydrogen migration (terminal-to-bridge and bridge-to-terminal) and group migration (BH, CH, and CH2). The rearrangement of 1,3-diamino-1,3-diboretene (1 NH2) to 1,2-diamino-1,2-diboretene (2-NH2) was computed and compared to the rearrangement in the parent (1-->2). The effect of the amino group is to substantially increase the barrier height and stabilize the product, 2-NH2. PMID- 11196913 TI - Synthesis and characterization of mixed-ligand oxorhenium complexes with the SNN type of ligand. Isolation of a novel ReO[SN][S][S] complex. AB - A new series of mixed-ligand oxorhenium complexes 4-9, with ligands 1-3 (L1H2) containing the SNN donor set and monodentate thiols as coligands (L2H), is reported. All complexes were synthesized using ReOCl3(PPh3)2 as precursor. They were isolated as crystalline products and characterized by elemental analysis and IR and NMR spectroscopy. The ligands 1 and 2 (general formula RCH2CH2NHCH2CH2SH, where R = N(C2H5)2 in 1 and pyrrolidin-1-yl in 2) act as tridentate SNN chelates to the ReO3+ core, leaving one open coordination site cis to the oxo group. The fourth coordination site is occupied by a monodentate aromatic thiol which acts as a coligand. Thus, three new "3 + 1" [SNN][S] oxorhenium complexes 4-6 (general formula ReO[RCH2CH2NCH2CH2S][SX], where R = N(C2H5)2 and X = phenyl in 4, R = N(C2H5)2 and X = p-methylphenyl in 5, and R = pyrrolidinlyl and X = p methylphenyl in 6) were prepared in high yield. Complex 4 adopts an almost perfect square pyramidal geometry (tau = 0.07), while 6 forms a distorted square pyramidal geometry (tau = 0.24). In both complexes 4 and 6, the basal plane is formed by the SNN donor set of the tridentate ligand and the S of the monodentate thiol. On the other hand, the ligand 3, [(CH3)2CH]2NCH2CH2NHCH2CH2SH, acts as a bidentate ligand, probably due to steric hindrance, and it coordinates to the ReO3+ core through the SN atoms, leaving two open coordination sites cis to the oxo group. These two vacant positions are occupied by two molecules of the monodentate thiol coligand, producing a novel type of "2 + 1 + 1" [SN][S][S] oxorhenium mixed-ligand complexes 7-9 (general formula ReO[[(CH3)2CH]2NCH2CH2NHCH2CH2S][SX][SX], where X = phenyl in 7, p-methylphenyl in 8, and benzyl in 9). The coordination sphere about rhenium in 7 and 8 consists of the SN donor set of ligand 3, two sulfurs of the two monodentate thiols, and the doubly bonded oxygen atom in a trigonally distorted square pyramidal geometry (tau = 0.44 and 0.45 for 7 and 8, respectively). Detailed NMR assignments were determined for complexes 5 and 8. PMID- 11196914 TI - Mercury(I) molybdates and tungstates: Hg2WO4 and two modifications of Hg2MoO4. AB - The high-temperature (beta-) modification of Hg2MoO4 was prepared by solid-state reaction of HgO with MoO2 at 400 degrees C. Well-crystallized samples of the low temperature (alpha-) modification of Hg2MoO4 and isotypic Hg2WO4 were obtained by hydrothermal recrystallization of the microcrystalline powders at 180 degrees C. The crystal structures of these transparent yellow compounds were determined by single-crystal X-ray diffractometry. beta-Hg2MoO4: P2(1)/c, Z = 4, a = 511.31(6) pm, b = 901.83(7) pm, c = 1086.0(1) pm, beta = 101.01(3) degrees. alpha-Hg2MoO4 and Hg2WO4: C2/c, Z = 4, a = 873.52(6) and 873.0(1) pm, b = 1155.19(7) and 1147.6(3) pm, c = 493.05(3) and 493.24(6) pm, beta = 115.196(5) degrees and 114.86(1) degrees, respectively. In beta-Hg2MoO4 the molybdenum atoms are tetrahedrally coordinated by oxygen atoms and the MoO4 tetrahedra are linked via Hg2 dumb-bells, thus forming infinite zigzag chains. The low-temperature (alpha )modification of Hg2MoO4 contains MoO6 octahedra, which are linked via common edges to form zigzag chains, which are further linked via Hg2 dumb-bells, resulting in puckered two-dimensionally infinite sheets. Bonding between adjacent sheets is achieved only via weak (secondary) Hg-O bonds of 254.8 pm, while the strong Hg-O bonds of the nearly linear O-Hg-Hg-O groups within the sheets have a length of 214.8 pm. The Hg-Hg bond lengths are practically the same in the three compounds with 252.3(1), 253.49(7), and 253.3(1) pm in beta-Hg2MoO4, alpha Hg2MoO4, and Hg2WO4, respectively. The average Mo-O distances within the MoO4 tetrahedra and the MoO6 octahedra are 176.2, and 196.5 pm, respectively. The structural chemistry of these compounds is discussed together with that of previously reported mercury I and II molybdates and tungstates. PMID- 11196915 TI - Preparation and oxygenation of (flavonolato)copper isoindoline complexes with relevance to quercetin dioxygenase. AB - Mesitylcopper reacts with flavonol (flaH) in the presence of 1,3-bis(2 pyridylimino)isoindoline (indH) to yield the diamagnetic complex CuI(fla)(indH), which on reaction with molecular oxygen undergoes oxidative splitting of the C2 C3 bond of the pyranone ring of the flavonolate ligand to give CuI(indH)(O-bs) (O bs = O-benzoylsalicylate) (orthorhombic, P1, a = 8.048(7) A, b = 8.969(9) A, c = 19.240(2) A, alpha = 85.69 degrees, beta = 80.24(7) degrees, gamma = 77.87(7) degrees, V = 1337(2) A3, Z = 2) and carbon monoxide. The reaction of [CuI(CH3CN)4]ClO4, flaH, and indH with dioxygen at room temperature affords the paramagnetic complex [CuII(fla)(indH)]ClO4 (mu = 2.10 mu B), and after elimination of HClO4, CuII(fla)(ind) (orthorhombic, Pbca, a = 8.888(2) A, b = 19.169(7) A, c = 33.614(10) A, alpha = beta = gamma = 90 degrees, V = 5727(3) A3, Z = 8) with mu = 1.86 mu B is formed. The latter undergoes cleavage of the pyranone ring on oxygenation at 80 degrees C to give CuII(ind)(O-bs) (mu = 1.87 mu B, nu(CO) = 1742 cm-1, and nu(CO2) = 1581, 1387 cm-1) and carbon monoxide. CuII(fla)(ind) and [CuII(fla)(indH)]ClO4 serve as good catalysts for the oxygenation of flavonol to O-benzoylsalicyclic acid. PMID- 11196916 TI - New antitumor-active azole-bridged dinuclear platinum(II) complexes: synthesis, characterization, crystal structures, and cytotoxic studies. AB - Three new derivatives of the cytotoxic azole-bridged dinuclear platinum(II) complex [(cis-Pt(NH3)2)2(mu-OH)(mu-pz)][NO3]2 (1) have been prepared and structurally characterized. Their formulas are [(cis-Pt(NH3)2)2(mu-OH)(mu-1,2,3 ta)][NO3]2 (2) (1,2,3-ta = 1,2,3-triazolate), [(Pt(R,R-dach))(mu-OH)(mu pz)(Pt(S,S- dach))][NO3]2 (3) (dach = 1,2-diaminocyclohexane, pz = pyrazolate), and [(Pt(R,R-dach))(mu-1,2,3- ta)2(Pt(S,S-dach))][NO3]2 (4). The compounds were characterized by 1H, 13C, and 195Pt NMR spectroscopy, and elemental analysis, and their crystal structures were determined. Relevant data for 2: triclinic, space group P1, a = 8.5225(15) A, b = 9.1977(18) A, c = 9.9771(7) A, alpha = 66.988(10) degrees, beta = 75.423(9) degrees, gamma = 67.321(13) degrees, Z = 2. 3: orthorhombic, space group Pca2(1), a = 17.7653(3) A, b = 12.4076(3) A, c = 10.7091(3) A, Z = 4. 4: orthorhombic, space group Pbca, a = 13.8944(1) A, b = 17.8668(1) A, c = 20.7647(2) A, Z = 8. In the crystal structures of 2, and 3, the intramolecular distances between the two Pt atoms are 3.4411(6) and 3.4873(5) A, and the dihedral angles between the platinum coordination planes are 14.1(3) and 9.3(4) degrees, respectively. In 2, an intramolecular hydrogen bond is observed between N9 of the ammine ligand and the noncoordinated nitrogen atom (N3) of the triazole ring (N9...N3: 2.962(10) A). 4 has a boat-form structure, and the two coordination planes cross at 83.64(10) degrees. A cytotoxicity assay of these dinuclear platinum(II) compounds on human tumor cell lines was performed. In most of the cell lines, 1 and 2 showed much higher cytotoxicity than those of cisplatin. On the other hand, 3 was found to be moderately active, and 4 was found only marginally cytotoxic. Implications of these findings are discussed in the context of a structure-activity relationship. PMID- 11196917 TI - Synthesis of SnSe in various alkaline media under mild conditions. AB - The synthesis of SnSe was systematically investigated in various alkaline media and at various temperatures with SnCl2.2H2O and selenium as source materials. The basicity of the alkaline media and the reaction temperature are two key factors considered in our process. The synthesis of SnSe in sodium hydroxide solution and aqueous ammonia is limited to a narrow temperature range, while the synthesis in hydrazine hydrate and ethylenediamine proceeds over a wider range. The final products were characterized by X-ray diffraction pattern (XRD), energy dispersive X-ray (EDX), and transmission electron microscopy (TEM). TEM results showed a variation of crystal morphology of SnSe obtained in different media. Two simple chemical mechanisms for the formation of SnSe are presented. PMID- 11196918 TI - Bis(mercaptoimidazolyl)(pyrazolyl)hydroborato complexes of zinc, cadmium, and cobalt: structural evidence for the enhanced tendency of zinc in biological systems to adopt tetrahedral M[S4] coordination. AB - The bis(2-mercapto-1-methylimidazolyl)(pyrazolyl)hydroborato derivatives [pzBmMe]2Zn, [pzBmMe]2Co, and [pzBmMe]2Cd have been isolated and structurally characterized by X-ray diffraction. Despite their common [pzBmMe]2M composition, each of these complexes adopts a different structure. Thus, (i) the zinc complex exhibits a tetrahedral Zn[S4] structure in which only the sulfur donors coordinate to zinc, (ii) the cobalt complex exhibits a trigonal-bipyramidal Co[S3NH] structure in which one of the pyrazolyl groups and one of the B-H groups coordinate to cobalt, and (iii) the cadmium complex exhibits a six-coordinate Cd[S4H2] structure in which both B-H groups interact with the cadmium center. These comparisons emphasize that zinc has a greater preference for tetrahedral M[S4] coordination than does either cobalt or cadmium, an observation that is in accord with the prevalent role of zinc in the structural sites of enzymes. PMID- 11196919 TI - The OsO4F-, OsO4F2(2)-, and OsO3F3- anions, their study by vibrational and NMR spectroscopy and density functional theory calculations, and the X-ray crystal structures of [N(CH3)4][OsO4F] and [N(CH3)4][OsO3F3]. AB - The fluoride ion acceptor properties of OsO4 and OsO3F2 were investigated. The salts [N(CH3)4][OsO4F] and [N(CH3)4]2[OsO4F2] were prepared by the reactions of OsO4 with stoichiometric amounts of [N(CH3)4][F] in CH3CN solvent. The salts [N(CH3)4][OsO3F3] and [NO][OsO3F3] were prepared by the reactions of OsO3F2 with a stoichiometric amount of [N(CH3)4][F] in CH3CN solvent and with excess NOF, respectively. The OsO4F- anion was fully structurally characterized in the solid state by vibrational spectroscopy and by a single-crystal X-ray diffraction study of [N(CH3)4][OsO4F]: Abm2, a = 7.017(1) A, b = 11.401(2) A, c = 10.925(2) A, V = 874.1(3) A3, Z = 4, and R = 0.0282 at -50 degrees C. The cis-OsO4F2(2-) anion was characterized in the solid state by vibrational spectroscopy, and previous claims regarding the cis-OsO4F2(2-) anion are shown to be erroneous. The fac-OsO3F3- anion was fully structurally characterized in CH3CN solution by 19F NMR spectroscopy and in the solid state by vibrational spectroscopy of its N(CH3)4+ and NO+ salts and by a single-crystal X-ray diffraction study of [N(CH3)4][OsO3F3]: C2/c, a = 16.347(4) A, b = 13.475(3) A, c = 11.436(3) A, beta = 134.128(4) degrees, V = 1808.1(7) A3, Z = 8, and R = 0.0614 at -117 degrees C. The geometrical parameters and vibrational frequencies of OsO4F-, cis-OsO4F2(2-), monomeric OsO3F2, and fac-OsO3F3- and the fluoride affinities of OsO4 and monomeric OsO3F2 were calculated using density functional theory methods. PMID- 11196920 TI - Ruthenium(II) complexes of redox-related, modified dipyridophenazine ligands: synthesis, characterization, and DNA interaction. AB - The synthesis, spectral characterization, and electrochemical properties of [Ru(phen)2(qdppz)]2+, which incorporates a quinone-fused dipyridophenazine ligand (naphtho[2,3-a]dipyrido[3,2-h:2',3'-f]phenazine-5,18-dione, qdppz), are described in detail. Chemical or electrochemical reduction of [Ru(phen)2(qdppz)]2+ leads to the generation of [Ru(phen)2(hqdppz)](2+)--a complex containing the hydroquinone form (hqdppz = 5,18-dihydroxynaphtho[2,3-a]-dipyrido[3,2-h:2',3'-f]phenazine) of qdppz. Absorption and viscometric titration, thermal denaturation, topoisomerase assay, and differential-pulse voltammetric studies reveal that [Ru(phen)2(qdppz)]2+ is an avid binder of calf-thymus DNA due to a strong intercalation by the ruthenium-bound qdppz, while [Ru(phen)2(hqdppz)]2+ binds to DNA less strongly than the parent "quinone"-containing complex. DNA-photocleavage efficiencies of these complexes also follow a similar trend in that the MLCT excited state of [Ru(phen)2(qdppz)]2+ is more effective than that of [Ru(phen)2(hqdppz)]2+ in cleaving the supercoiled plasmid pBR 322 DNA (lambda exc = 440 +/- 5 nm), as revealed by the results of agarose gel electrophoresis experiments. The photochemical behaviors of both the quinone- and hydroquinone appended ruthenium(II) complexes in the presence of DNA not only provide valuable insights into their modes of binding with the duplex but also lead to detailed investigations of their luminescence properties in nonaqueous, aqueous, and aqueous micellar media. On the basis of the results obtained, (i) a photoinduced electron transfer from the MLCT state to the quinone acceptor in Ru(phen)2(qdppz)]2+ and (ii) quenching of the excited states due to proton transfer from water to the dipyridophenazine ligand in both complexes are invoked to rationalize the apparent lack of emission of these redox-related complexes in the DNA medium. PMID- 11196921 TI - Ruthenium(II) complexes of 6,7-dicyanodipyridoquinoxaline: synthesis, luminescence studies, and DNA interaction. AB - The hexaflurophosphate and chloride salts of a series of ruthenium(II) complexes incorporating a new dipyridophenazine-based ligand, dicnq (6,7 dicyanodipyrido[2,2-d:2',3'-f]quinoxaline), are synthesized in good-to-moderate yields. These mono ([Ru(phen)2(dicnq)]2+; phen = 1,10-phenanthroline), bis ([Ru(phen)(dicnq)2]2+), and tris ([Ru(dicnq)3]2+) complexes are fully characterized by elemental analysis, infrared, FAB-MS, 1H NMR, and cyclic voltammetric methods. Results of absorption titration and thermal denaturation studies reveal that these complexes are moderately strong binders of calf-thymus (CT) DNA, with their binding constants spanning the range (1-3) x 10(4) M-1. On the other hand, under the identical set of experimental conditions of light and drug dose, the DNA (pBR 322)-photocleavage abilities of these ruthenium(II) complexes follow the order [Ru(phen)2(dicnq)]2+ > [Ru(phen)(dicnq)2]2+ >> [Ru(dicnq)3]2+, an order which is the same as that observed for their MLCT emission quantum yields. Steady-state emission studies carried out in nonaqueous solvents and in aqueous media with or without DNA reveal that while [Ru(dicnq)3]2+ is totally nonemissive under these solution conditions, both [Ru(phen)2(dicnq)]2+ and [Ru(phen)(dicnq)2]2+ are luminescent and function as "molecular light switches" for DNA. Successive addition of CT DNA to buffered aqueous solutions containing the latter two complexes results in an enhancement of the emission in each case, with the enhancement factors at saturation being approximately 16 and 8 for [Ru(phen)2(dicnq)]2+ and [Ru(phen)(dicnq)2]2+, respectively. These results are discussed in light of the relationship between the structure-specific deactivations of the MLCT excited states of these metallointercalators and the characteristic features of their DNA interactions, and attempts are made to compare and contrast their properties with those of analogous dipyridophenazine-based complexes, including the ones reported in the preceding paper. PMID- 11196922 TI - 2-D interwoven and 3-D 5-fold interpenetrating silver(I) complexes of 1 (isocyanidomethyl)-1H-benzotriazole and 1,3-bis(dicyanomethylidene)indan. AB - This paper presents novel and distinctive organosilver polymers with intriguing structure motifs, constructed from iodoacetonitrile (L1), 1-(isocyanidomethyl)-1H benzotriazole (L2), 1,3-bis(dicyanomethylidene)indan (L3), and silver(I) salts, respectively. Treatment of L1 with AgClO4 generated [Ag(L1)(ClO4)]n (1), whose X ray determination revealed a 2-D wavy sheet structure with square grids. Reaction of L2 with AgPF6 gave rise to a novel 2-D wavy interwoven network, ([Ag(L2)(PO2F2)0.5])n (2). The complex [Ag2(L3)2]n (3) obtained by reaction of AgClO4 with L3 can be regarded as unprecedented 3-D 5-fold interpenetrating nets with columnar aromatic stacks and indicates semiconductive behavior. The IR, ESR spectroscopic results, conductivities, and structural features of the complexes are discussed, respectively. The present findings may provide insight into the coordination versatility of silver(I) and polynitrile ligands and an inspiration for the self-assembly of novel supramolecular networks with multifunctional ligands. Crystal data: 1, C2H2AgINClO4, orthorhombic, Pca2(1) (No. 29), a = 14.503(1) A, b = 5.104(2) A, c = 10.2019(9) A, Z = 4; 2, C8H6AgN4PF4O, orthorhombic, Pnna (No. 52), a = 12.2705(3) A, b = 21.150(1) A, c = 10.040(1) A, Z = 8; 3, C30H10Ag2N8, triclinic, P1 (No. 2), a = 14.920(2) A, b = 11.896(2) A, c = 7.400(4) A, alpha = 86.55(2) degrees, beta = 80.87(2) degrees, gamma = 74.47(1) degrees, Z = 2. PMID- 11196923 TI - Synthesis, structure, luminescence, and theoretical studies of tetranuclear gold clusters with phosphinocarborane ligands. AB - Treatment of the tetranuclear gold cluster [Au4((PPh2)2C2B9H10)2(AsPh3)2] (1), which contains the nido-carborane-diphosphine [7,8-(PPh2)2C2B9H10]-, with various tertiary phosphines leads to derivatives [Au4((PPh2)2C2B9H10)2-(PR3)2] (PR3 = PPh3 (2), P(4-MeC6H4)3 (3), P(4-OMeC6H4)3 (4)). The X-ray crystal structure of complex 4 shows a tetrahedral framework of gold atoms, two of which are chelated by the diphosphine, and two are coordinated to one monophosphine ligand each. These compounds are very stable and are obtained in high yield. MP2 calculations suggest that the two types of chemically nonequivalent gold atoms can be formally assigned as Au(I) (those attached to the arsines or phosphines) and Au(0) (those bonded to the anionic diphosphine) and emphasize the role of correlation in the gold-gold interactions. The compounds are luminescent. The emission is assigned to a gold-centered spin-forbidden transition; the assignment of the oxidation state of the gold centers on this basis leads to results coincident with those obtained by theoretical calculations. PMID- 11196924 TI - Kinetics and mechanism for reversible chloride transfer between mercury(II) and square-planar platinum(II) chloro ammine, aqua, and sulfoxide complexes. Stabilities, spectra, and reactivities of transient metal-metal bonded platinum mercury adducts. AB - The Hg2+aq- and HgCl+aq-assisted aquations of [PtCl4]2- (1), [PtCl3(H2O)]- (2), cis-[PtCl2(H2O)2] (3), trans-[PtCl2(H2O)2] (4), [PtCl(H2O)3]+ (5), [PtCl3Me2SO]- (6), trans-[PtCl2(H2O)Me2SO] (7), cis-[PtCl(H2O)2Me2SO]+ (8), trans [PtCl(H2O)2M32SO]+ (9), trans-[PtCl2(NH3)2] (10), and cis-[PtCl2(NH3)2] (11) have been studied at 25.0 degrees C in a 1.00 M HClO4 medium buffered with chloride, using stopped-flow and conventional spectrophotometry. Saturation kinetics and instantaneous, large UV/vis spectral changes on mixing solutions of platinum complex and mercury are ascribed to formation of transient adducts between Hg2+ and several of the platinum complexes. Depending on the limiting rate constants, these adducts are observed for a few milliseconds to a few minutes. Thermodynamic and kinetics data together with the UV/vis spectral changes and DFT calculations indicate that their structures are characterized by axial coordination of Hg to Pt with remarkably short metal-metal bonds. Stability constants for the Hg2+ adducts with complexes 1-6, 10, and 11 are (2.1 +/- 0.4) x 10(4), (8 +/- 1) x 10(2), 94 +/- 6, 13 +/- 2, 5 +/- 2, 60 +/- 6, 387 +/- 2, and 190 +/- 3 M-1, respectively, whereas adduct formation with the sulfoxide complexes 7-9 is too weak to be observed. For analogous platinum(II) complexes, the stabilities of the Pt-Hg adducts increase in the order sulfoxide << aqua < ammine complex, reflecting a sensitivity to the pi-acid strength of the Pt ligands. Rate constants for chloride transfer from HgCl+ and HgCl2 to complexes 1-11 have been determined. Second-order rate constants for activation by Hg2+ are practically the same as those for activation by HgCl+ for each of the platinum complexes studied, yet resolved contributions for Hg2+ and HgCl+ reveal that the latter does not form dinuclear adducts of any significant stability. The overall experimental evidence is consistent with a mechanism in which the accumulated Pt(II)-Hg2+ adducts are not reactive intermediates along the reaction coordinate. The aquation process occurs via weaker Pt-Cl-Hg or Pt-Cl-HgCl bridged complexes. PMID- 11196925 TI - Formation of one-, two-, and three-dimensional open-framework zinc phosphates in the presence of a tetramine. AB - Five new open-framework zinc phosphates, encompassing the entire hierarchy of open-framework structures, have been synthesized hydrothermally in the presence of triethylenetetramine. The structures include one-dimensional ladders, two dimensional layers, and three-dimensional structures as well as a zinc phosphate where the amine acts as a ligand. [C6N4H22]0.5[Zn(HPO4)2] (I): monoclinic, space group P2(1)/c (no. 14), a = 5.2677(1) A, b = 13.3025(1) A, c = 14.7833(1) A, beta = 96.049 degrees, Z = 4. [C6N4H22]0.5[Zn2(HPO4)3] (II): triclinic, space group P1 (no. 2), a = 7.515(1) A, b = 8.2553(1) A, c = 12.911(1) A, alpha = 98.654(1) degrees, beta = 101.274(1) degrees, gamma = 115.791(1) degrees, Z = 2. [C6N4H22]0.5[Zn2P2O8] (III): triclinic, space group P1 (no. 2), a = 8.064(1) A, b = 8.457(1) A, c = 9.023(1) A, alpha = 111.9(1) degrees, beta = 108.0(1) degrees, gamma = 103.6(1) degrees, Z = 2. [C6N4H22]0.5[Zn3(PO4)2(HPO4)] (IV): triclinic, space group P1 (no. 2), a = 5.218(1) A, b = 8.780(1) A, c = 16.081(1) A, alpha = 89.3(1) degrees, beta = 83.5(1) degrees, gamma = 74.3(1) degrees, Z = 2. [C6N4H20]0.5[Zn4P4O16] (V): monoclinic, space group P2(1)/c (no. 14), a = 9.219(1) A, b = 15.239(1) A, c = 10.227(1) A, beta = 105.2(1), Z = 4. The structure of I is composed of ZnO4 and HPO4 tetrahedra, which are edge-shared to form four-membered rings, which, in turn, form a one-dimensional chain (ladder). In II, these ladders are fused into a layer. The structures of III and IV comprise networks of ZnO4 and PO4 tetrahedra forming three-dimensional architectures. In V, the amine molecule coordinates to the Zn and acts as a pillar supporting the zinc phosphate layers, which possess infinite Zn-O-Zn linkages. The 16-membered one-dimensional channel in IV and the ZnO3N pillar, along with infinite Zn-O-Zn linkages in V, are novel features. The structure of the open-framework zinc phosphates is found to depend sensitively on the relative concentrations of the amine and phosphoric acid, with high concentrations of the latter favoring structures with lower dimensions. PMID- 11196926 TI - Influence of hydrogen bonding on the assembly of six-membered vanadium borophosphate cluster anions: synthesis and structures of (NH4)2(C2H10N2)6[Sr(H2O)5]2[V2P2BO12](6)10H2O, (NH4)2(C3H12N2)6[Sr(H2O)4]2[V2P2BO12](6)17H2O, and (NH4)3(C4H14N2)4 5[Sr(H2O)5]2[Sr(H2O)4][V2P2BO12]6 10H2O. AB - Three new strontium vanadium borophosphate compounds, (NH4)2(C2H10N2)6[Sr(H2O)5]2[V2P2BO12]6 10H2O (Sr-VBPO1) (1), (NH4)2(C3H12N2)6[Sr(H2O)4]2[V2P2BO12]6 17H2O (Sr-VBPO2) (2), and (NH4)3(C4H14N2)4.5[Sr(H2O)5]2[Sr(H2O)4][V2P2BO12]6 10H2O (Sr-VBPO3) (3) have been synthesized by interdiffusion methods in the presence of diprotonated ethylenediamine, 1,3-diaminopropane, and 1,4-diaminobutane. Compound 1 has a chain structure, whereas 2 and 3 have layered structures with different arrangements of [(NH4) [symbol: see text] [V2P2BO12]6] cluster anions within the layers. Crystal data: (NH4)2(C2H10N2)6[Sr(H2O)5]2[V2P2BO12]6 10H2O, monoclinic, space group C2/c (no. 15), a = 21.552(1) A, b = 27.694(2) A, c = 20.552(1) A, beta = 113.650(1) degrees, Z = 4; (NH4)2(C3H12N2)6[Sr(H2O)4]2[V2P2BO12]6 17H2O, monoclinic, space group I2/m (no. 12), a = 15.7618(9) A, b = 16.4821(9) A, c = 21.112(1) A, beta = 107.473(1) degrees, Z = 2; (NH4)3(C4H14N2)4.5[Sr(H2O)5]2[Sr(H2O)4] [V2P2BO12]6 10H2O, monoclinic, space group C2/c (no. 15), a = 39.364(2) A, b = 14.0924(7) A, c = 25.342(1) A, beta = 121.259(1) degrees, Z = 4. The differences in the three structures arise from the different steric requirements of the amines that lead to different amine-cluster hydrogen bonds. PMID- 11196927 TI - Ligand influences of the structures of molybdenum oxide networks. AB - The influence of organonitrogen ligands on the network structure of molybdenum oxides was examined by preparing three new molybdenum oxide phases [MoO3(4,4' bpy)0.5] (MOXI-8), [HxMoO3(4,4'-bpy)0.5] (MOXI-9), and [MoO3(triazole)0.5] (MOXI 32). The structure of [MoO3(4,4'-bpy)0.5) consists of layers of corner-sharing MoO5N octahedra, buttressed by bridging 4,4'-bipyridyl ligands into a three dimensional covalently bonded organic-inorganic composite material. Partial reduction of [MoO3(4,4'-bpy)0.5] yields the mixed-valence material [HxMoO3(4,4' bpy)0.5] (x approximately 0.5). The most apparent structural change upon reduction is found in the Mo-ligand bond lengths of the MoO5N octahedra, which exhibit the usual (2 + 2 + 2) pattern in [MoO3(4,4'-bpy)0.5] and a more regular (5 + 1) pattern in [HxMoO3(4,4'-bpy)0.5]. Substitution of triazole for 4,4' bipyridine yields [MoO3(triazole)0.5], which retains the layer motif of corner sharing MoO5N octahedra but with distinct sinusoidal ruffling in contrast to planar layers of [MoO3(4,4'-bpy)0.5] and [HxMoO3(4,4'-bpy)0.5]. The folding reflects the ligand constraints imposed by the triazole ligand that bridges adjacent Mo sites within a layer. MOXI-8, C5H4NMoO3: monoclinic P2(1)/c, a = 7.5727(6) A, b = 7.3675(7) A, c = 22.433(3) A, beta = 90.396(8) degrees, Z = 8. MOXI-9, C5H4.5NMoO3: monoclinic I2/m, a = 5.2644(4) A, b = 5.2642(4) A, c = 22.730(2) A, beta = 90.035(1) degrees, Z = 4. MOXI-32, C2H3N3Mo2O6: orthorhombic Pbcm, a = 3.9289(5) A, b = 13.850(2) A, c = 13.366(2) A, Z = 4. PMID- 11196928 TI - Multiple-path dissociation mechanism for mono- and dinuclear tris(hydroxamato)iron(III) complexes with dihydroxamic acid ligands in aqueous solution. AB - Linear synthetic dihydroxamic acids ([CH3N(OH)C=O)]2(CH2)n; H2Ln) with short (n = 2) and long (n = 8) hydrocarbon-connecting chains form mono- and dinuclear complexes with Fe(III) in aqueous solution. At conditions where the formation of Fe2(Ln)3 is favored, complexes with each of the two ligand systems undergo [H+] induced ligand dissociation processes via multiple sequential and parallel paths, some of which are common and some of which are different for the two ligands. The pH jump induced ligand dissociation proceeds in two major stages (I and II) where each stage is shown to be comprised of multiple components (Ix, where x = 1-3 for L2 and L8, and IIy, where y = 1-3 for L2 and y = 1-4 for L8). A reaction scheme consistent with kinetic and independent ESI-MS data is proposed that includes the tris-chelated complexes (coordinated H2O omitted for clarity) (Fe2(Ln)3, Fe2(L2)2(L2H)2, Fe(LnH)3, Fe(L8)(L8H)), bis-chelated complexes (Fe2(Ln)2(2+), Fe(LnH)2+, Fe(L8)+), and monochelated complexes (Fe(LnH)2+). Analysis of kinetic data for ligand dissociation from Fe2(Ln)(LnH)3+ (n = 2, 4, 6, 8) allows us to estimate the dielectric constant at the reactive dinuclear Fe(III) site. The existence of multiple ligand dissociation paths for the dihydroxamic acid complexes of Fe(III) is a feature that distinguishes these systems from their bidentate monohydroxamic acid and hexadentate trihydroxamic acid counterparts and may be a reason for the biosynthesis of dihydroxamic acid siderophores, despite higher environmental molar concentrations necessary to completely chelate Fe(III). PMID- 11196929 TI - Chemistry of metal-bound anion radicals. A family of mono- and bis(azopyridine) chelates of bivalent ruthenium. AB - The reaction of the dihydride [RuII(H)2(CO)(PPh3)3], 3, with excess azo-2,2' bipyridine (abp) in boiling dry benzene has afforded the diradical bischelate [RuII(abp.-)2(CO)(PPh3)], 4, and the hydridic monochelate monoradical [RuII(abp. )(H)(CO)(PPh3)2], 5. A similar reaction between 3 and 2-(p chlorophenylazo)pyridine (Clpap) did not yield a bischelate, but the hydridic monoradical [RuII(Clpap.-)(H)(CO)(PPh3)2], 6, has been isolated. Upon treatment of 4-6 with NH4PF6 in a wet dichloromethane-acetonitrile medium, the one-electron oxidized salts 4+PF6-, 5+PF6-, and 6+PF6- are isolated, H+ being the oxidizing agent. The X-ray structures of 4+PF6-.CH2Cl2, 5+PF6-.H2O, and 6+PF6- have been determined. In the monoradical 4+ the azo N-N bond lengths in the two chelate rings are 1.284(6) and 1.336(6) A, showing that the radical electron is localized in the latter ring. The half-filled extended Huckel HOMO is indeed found to be so localized, and it has a large azo character. Complexes 4-6 display radical redox couples with E1/2 in the range -0.5 to +0.10 V vs SCE. The E1/2 values qualitatively correlate with corresponding vco values (1900-2000 cm-1). The monoradicals (S = 1/2) 4+, 5, and 6 uniformly display a strong EPR signal near g = 2.00. Metal-mediated magnetic interaction makes the EPR-silent diradical 4 strongly antiferromagnetic with J = -299 cm-1. Crystal data are as follows: (4+PF6-.CH2Cl2, C40H33Cl2F6N8-OP2Ru) monoclinic, space group P2(1)/c (no. 14), a = 14.174(6) A, b = 16.451(4) A, c = 18.381(4) A, beta = 98.00(3) degrees, Z = 4; (5+PF6-.H2O, C47H41F6N4O2P3Ru) monoclinic, space group P2(1)/n (no. 14), a = 9.433(2) A, b = 38.914(17) A, c = 13.084(3) A, beta = 103.47(2) degrees, Z = 4; (6+PF6-, C48H39ClF6N3OP3Ru) monoclinic, space group P2(1)/n (no. 14), a = 10.496(5) A, b = 22.389(8) A, c = 19.720(6) A, beta = 90.53(3) degrees, Z = 4. PMID- 11196930 TI - Mixed hydroxypyridinonate ligands as iron chelators. AB - New ligands based on hydroxypyridinonate (HOPO) and other bidentate ligands are explored as iron(III) sequestering agents. These are based on the N,N',N"-tris[(3 hydroxy-1-methyl- 2-oxo-1,2-didehydropyrid-4-yl)-carboxamidoethyl]amine (TREN-Me 3,2-HOPO) platform in which one Me-3,2-HOPO ligand group is substituted with either a 2-hydroxyisophthalamide (TREN-Me-3,2-HOPOIAM) or a 2,3 dihydroxyterephthalamide (TREN-Me-3,2-HOPOTAM) moiety. The ferric complexes have been prepared and structurally characterized by X-ray diffraction: Fe[TREN-Me-3,2 HOPOIAM] crystallizes in the monoclinic space group C2/c with cell parameters a = 18.1186(3) A, b = 17.5926(2) A, c = 25.0476(2) A, beta = 98.142(1) degrees, Z = 8. Fe[TREN-Me-3,2-HOPOTAM]- crystallizes in the monoclinic space group C2/c with cell parameters a = 31.7556(12) A, b = 14.0087(6) A, c = 22.1557(9) A, beta = 127.919(1) degrees, Z = 8. The aqueous coordination chemistry of these ligands with both the ferric and ferrous redox states of iron has been examined using spectroscopic and electrochemical methods, giving log formation constants of 26.89(3) (beta 110), 31.16(6) (beta 111) for the ferric TREN-Me-3,2-HOPOIAM complexes and 33.89(2) (beta 110), 38.45(2) (beta 111) for the ferric TREN-Me-3,2 HOPOTAM complexes. For the reduced (ferrous) complexes values of 10.03(9) (beta 110) and 13.7(2) (beta 110) were observed for the Fe[TREN-Me-3,2-HOPOIAM]- and Fe[TREN-Me-3,2-HOPOTAM]2- complexes, respectively. These data provide a complete description of metal-ligand speciation as a function of pH and of redox activity. The ligands described in this work are part of a new class of heteropodate ligands which exploit the various chelating properties of several binding units within a single tripodal ligand and allow for systematic variation of the properties for medical or other applications. PMID- 11196931 TI - Synthetic models for the zinc sites in the methionine synthases. AB - The syntheses and molecular structures of a series of tetrahedral zinc complexes designed to model the active sites in Escherichia coli methionine synthases are reported. [PhTttBu]ZnBr (PhTttBu = phenyltris((tert-butylthio)-methyl)borate) was prepared and characterized crystallographically to provide entry into [S3]ZnX complexes. Metathesis with KSPh yielded the phenylthiolato complex, [PhTttBu]Zn(SPh), which represents a structural mimic of the homocysteine ligated form of the enzyme. Alternatively, [S2N]ZnX (X = Br, CH3, SPh) species were prepared using the new mixed-donor ligands, [Ph(pz)BttBu] (phenyl(pyrazolyl)bis((tert-butylthio)methyl)borate) and [Ph(pztBu)BttBu] (phenyl(3-tert-butylpyrazolyl)bis((tert- butylthio)methyl)borate). Protonolysis of [Ph(pztBu)-BttBu]Zn(CH3) by PhSH in toluene yielded [Ph(pztBu)BttBu]Zn(SPh), a synthetic analogue of the homocysteine ligated form of cobalamin-independent methionine synthase (Met E). The average Zn-S bond distance in [Ph (pztBu)BttBu]Zn(SPh) of 2.37 A compares well with the EXAFS-derived distance of 2.31 A found in the homocysteine-bound form of Met E. PMID- 11196932 TI - Heterogeneous electron-transfer rate constants for M2(O2CR)4(0)/+, where M = Mo, W, Ru, or Rh and R = alkyl or aryl. AB - By the use of Nicholson's method, the heterogeneous electron-transfer rate constants (ks) for the oxidation of a series of M2(O2CR)4 complexes have been determined in benzonitrile, where the metal M = Mo, W, Ru, or Rh and R = alkyl or aryl. For R = tBu, the values of ks follow the order M = Mo > W > Ru > Rh. No simple influence of R on ks was observed, although added ligands that are known to reversibly bind to the dinuclear center were shown to influence the E1/2 values in order of their basicity and to suppress the rate of electron transfer. The reported data are compared with those obtained for Cp2Fe0/+, Cp2*Fe0/+, and Ru(bpy)2(2)+/3+ and with earlier work on dirhenium multiply bonded compounds. PMID- 11196933 TI - Synthesis, structure, and H2O2-dependent catalytic functions of disulfide-bridged dicopper(I) and related thioether-copper(I) and thioether-copper(II) complexes. AB - A disulfide-bridged dicopper(I) complex, [Cu2(Py2SSPy2)](ClO4)2 (1) (Py2SSPy2 = bis(2-[N,N-bis(2-pyridylethyl)-amino]-1,1- dimethylethyl)disulfide), a thioether copper(I) complex, [Cu(iPrSPy2)](ClO4) (2) (iPrSPy2 = N-(2-isopropylthio-2 methyl)propyl-N,N-bis-2-(2-pyridyl)ethylamine, and a thioether-copper(II) complex, [Cu-(PheSPy2)(H2O)](ClO4)2 (3) (PheSPy2 = N-(2-methyl-2 phenethylthio)propyl-N,N-bis-2-(2- pyridyl)ethylamine), were newly synthesized by the reactions of Cu(ClO4)2.6H2O with a thiol ligand of Py2SH (N,N-bis[2-(2 pyridyl)-ethyl]-1,1-dimethyl-2- mercaptoethylamine) and thioether ligands of iPrSPy2 and PheSPy2, respectively. For complexes 1 and 2, X-ray analyses were performed. Complex 1 crystallizes in the triclinic space group P1, and complex 2 crystallizes in the orthorhombic space group Pbca with the following unit cell parameters: for 1, a = 15.165 (3) A, b = 22.185 (4) A, c = 14.989 (3) A, alpha = 105.76 (1) degrees, beta = 90.82 (2) degrees, gamma = 75.23 (1) degrees, and Z = 2; for 2, a = 17.78 (2) A, b = 17.70 (1) A, c = 15.75 (1) A, and Z = 8. Complex 1 is the first structurally characterized example obtained by the redox reaction Cu(II) + RSH-->Cu(I) + RSSR and has two independent structures (1a, 1b) which mainly differ in S-S bond distances, Cu(I)...Cu(I) separations, and C-S-S-C dihedral angles of the disulfide units. The S-S bond distances of 2.088(7) A in 1a and 2.070(7) A in 1b are indicative of significant activation of the S-S bonds by the dicopper centers. Fragment molecular orbital (FMO) analyses and molecular orbital overlap population (MOOP) analyses based on the extended Huckel method clarify the preferable formation of the disulfide S-S bond in 1 rather than the formation of a thiolate-copper(II) complex within the Py2S- ligand framework. Catalytic functions of complexes 1-3 were investigated with peroxides (H2O2 and tBuOOH) as oxidants. Complex 1 catalyzed the selective oxidation of cyclohexane to cyclohexanol and mediated the cyclohexene epoxidation in the presence of H2O2. A transient dark green intermediate observed in the reaction of 1 with H2O2 is characterized by UV-vis, EPR, and resonance Raman spectroscopies, identifying it as a Cu(II)-OOH species, 1(OOH). The resonance Raman features of the nu(O-O) bands at 822 and 836 cm-1, which are red-shifted to 781 and 791 cm-1, respectively, upon introduction of H2(18)O2, are indicative of formation of two kinds of Cu-OOH species rather than the Fermi doublet and the significant weakening of the O-O bonds. These mechanistic studies demonstrate that by virtue of the electron-donating ability of the disulfide unit the Cu-OOH species can be actually activated for one-electron oxidation, which has been reported so far unfavorable for other vibrationally characterized Cu-OOH species. PMID- 11196934 TI - Synthesis and crystal structure determination of a new pressure-induced iridium ditelluride phase, m-IrTe2, and comparison of the crystal structures and relative stabilities of various IrTe2 polymorphs. AB - The new monoclinic IrTe2 phase m-IrTe2 was synthesized under pressure, and its structure was determined by X-ray powder diffraction. The relative stabilities of the three known and three hypothetical IrTe2 polymorphs were discussed on the basis of tight binding electronic band structure calculations. m-IrTe2 exhibits structural features of both CdI2- and pyrite-type IrTe2 phases and is expected to be nearly as stable as that of the CdI2-type IrTe2. The hypothetical IrS2- and ramsdellite-type IrTe2 phases are predicted to be more stable than the CdI2-type IrTe2. PMID- 11196935 TI - Synthesis and characterization of a novel asymmetric ferrocene alkoxycarboxylate of titanium, Ti4O2(OiPr)6(eta 5-O2CC5H4)Fe(eta 5-C5H5))6. PMID- 11196936 TI - Interaction of [Pt(en)(phen)]2+ and [Pt(en)(phi)]2+ with the hexanucleotide d(GTCGAC)2: evidence for minor groove binding. PMID- 11196937 TI - Hydrothermal evolution of the thiourea-cerium(III) nitrate system: formation of cerium hydroxycarbonate and hydroxysulfate. PMID- 11196938 TI - Structural, electronic, and magnetic properties of (Fe[HC(3,5-Me2pz)3]2)(BF4)2 (pz = pyrazolyl): observation of unusual spin-crossover behavior. PMID- 11196939 TI - An isolable, oxygen-coordinated silver(I) complex of dimethyl diazomalonate: synthesis and characterization of [HB(3,5-(CF3)2Pz)3]Ag[OC(OCH3)]2CN2 (where Pz = pyrazolyl). PMID- 11196940 TI - Calixarenes as scaffolds: introduction of tridentate rare earth metal binding units into calix[4]arene. AB - The reactions of various derivatives of chelidamic acid (4-hydroxypyridine-2,6 dicarboxylic acid) with p-tert-butylcalix[4]arene have produced several new mono- and difunctionalized derivatives of the calixarene in which tridentate functional groups suitable for the binding of rare earth metal cations have been incorporated. Single-crystal X-ray structure determinations have been performed on two difunctionalized calixarenes found to adopt different "cone" and "1,2 alternate" conformations, as well as on a complex of europium(III) with the phenoxide form of a monofunctionalized ligand, this structure confirming that charge factors are dominant in determining the site of lanthanide metal binding in these ligands. PMID- 11196941 TI - Synthesis, structural characterization, and Monte Carlo simulation of the magnetic properties of two new alternating MnII azide 2-D honeycombs. Study of the ferromagnetic ordered phase below 20 K. AB - Reaction of MnII and pyridine derivatives such as 4-methylpyridine (4-Mepy) and 4 ethylpyridine (4-Etpy) led to the new two-dimensional systems trans-[Mn(4 Mepy)2(N3)2]n (1) and trans-[Mn(4-Etpy)2(N3)2]n (2). Compound 1 crystallizes in the triclinic system, P1 group (a = 9.269(2) A, b = 9.635(3) A, c = 18.860(4) A, Z = 4), and compound 2 crystallizes in the monoclinic system, P2(1)/c group (a = 14.416(3) A, b = 8.515(2) A, c = 15.728(4) A, Z = 4). The two compounds show honeycomb structures based on dinuclear Mn-(mu-N3)2-Mn subunits linked to the four nearest-neighbor similar subunits by four end-to-end single azido bridges, but whereas the subunits of compound 1 show the end-to-end Mn-(mu 1,3-N3)2-Mn kind of bridges, compound 2 prefers the end-on Mn-(mu 1,1-N3)2-Mn fragment. Magnetically, compound 1 is an alternating 2-D system with two different antiferromagnetic interactions, whereas compound 2 corresponds to a two dimensional ferro-antiferromagnetic system showing spin canting and permanent magnetization below 20 K. The coupling constant parameters J1 = -10.1 cm-1, J2 = 4.7 cm-1, and g = 2.019 for 1 and J1 = -5.3 cm-1, J2 = 2.9 cm-1, and g = 2.016 for 2 have been obtained from calculations using the Monte Carlo method based on the Metropolis algorithm. PMID- 11196942 TI - Reactions of M(CO)5X (M = Mn, Re; X = Cl, Br) with (Ph2PCH2)3CCH3 (P3) and (Ph2P(CH2)2)3P (P3P'): synthetic, spectroscopic, electrochemical, and electrospray mass spectrometric studies. AB - The reactions of M(CO)5X (M = Mn, Re; X = Cl, Br) with (Ph2PCH2)3CCH3 (P3) and (Ph2P(CH2)2)3P (P3P') are investigated, and the products are characterized by IR, NMR (31P and 13C), and electrospray mass spectrometric (ESMS) techniques. With P3, the major products are fac-M(CO)3(eta 2-P3)X (syn and anti isomers) and cis,fac-M(CO)2(eta 3-P3)X, and with P3P', the major product for each metal is cis,mer-M(CO)2(eta 3-P3P')X, but cis-[M(CO)2(eta 4-P3P')]X and fac-[Re(CO)3(eta 3 P3P')]X are also characterized. Addition of MeI to those complexes containing pendant phosphine groups produces the corresponding phosphonium cations without affecting the remainder of the molecule. On the voltammetric time scale, electrochemical oxidation of cis,fac-Mn(CO)2(eta 3-P3)X yields the corresponding 17e cation cis,fac-[Mn(CO)2(eta 3-P3)X]+, but on the longer time scale of exhaustive electrolysis or chemical oxidation, the product is fac-[Mn(CO)3(eta 3 P3)]+. In contrast, the rhenium cation cis,fac-[Re(CO)2(eta 3-P3)X]+ is stable on the synthetic time scale, but upon oxidation of cis,fac-Re(CO)2(eta 3-P3)X with NOBF4, the final product is the 18e [Re(CO)(NO)(eta 3-P3)X]+. cis,mer-Mn(CO)2(eta 3-P3P')X is reversibly oxidized to cis,mer-[Mn(CO)2(eta 3-P3P')X]+ on the voltammetric time scale, but on the longer synthetic time scale, the product isomerizes to trans-[Mn(CO)2(eta 3-P3P')X]+, which can be reduced to trans Mn(CO)2(eta 3-P3P')X. Upon voltammetric oxidation, the corresponding rhenium complexes show an initial irreversible response associated with the pendant phosphine group prior to the reversible oxidation of the metal on the synthetic time scale; spectroscopic data indicate formation of cis,mer-Re(CO)2(eta 3 P3P'O)X. The complex cis,mer-[Re(CO)2(eta 3-P3P'Me)X]+ shows only the reversible metal oxidation response. ESMS data are obtained directly for the methylated cationic complexes, and neutral complexes are either oxidized or adducted with sodium ions to produce cationic species. PMID- 11196943 TI - Main-group-element calix[4]arenes: variable coordination and conformational isomerism at phosphorus and silicon. AB - Treatment of calix[4]arene (1b) with trichloromethylsilane yields two conformers of calix[4]SiMe(OH), the cone 2b-C and the partial cone 2b-PC. These are isolated and structurally characterized, and their thermodynamic activation parameters are determined in solution [Ea = 117(3) kJ/mol, delta H = 5(4) kJ/mol]. Similar parameters are found for the p-tert-butylcalix[4]arene analogues 2a-C and 2a-PC. Deprotonation of 2b with butyllithium yields calix[4]SiMe(OLi) (8b). The structure of 8b is solvent dependent: 8b contains a five-coordinate silicon in THF and a four-coordinate silicon in benzene. Similar behavior is found for the p tert-butylcalix[4]arene analogues. The five-coordinate phosphorus analogue of the anion in 8, p-tert-butylcalix[4]PMe (11a), is synthesized from the phosphonium triflate salt p-tert-butylcalix[4]PMe(OH)OTf (10a(OTf)) via treatment with butyllithium. The structure of 11a shows the geometry around phosphorus to be very close to a pure trigonal bipyramid. The X-ray structure of 10a(OTf) cannot be obtained, but its iodide analogue 10a(T) is synthesized and structurally characterized. The cation in 10a(I) adopts the partial cone conformation in the solid state, similar to 2b-PC. Treatment of 8b with methyl trifluoromethanesulfonate yields the methyl phenyl ether calix[4]SiMe(OMe) (3b). This species and its p-tert-butyl analogue 3a are structurally characterized. Both adopt the partial cone conformation. The SiMe group in 3b can be removed via treatment with fluoride to yield the monomethylated calix[4]arene 4b in 50-60% overall yield based on 1b. PMID- 11196944 TI - Yttrium calix[4]arene complexes. Silylation and silylamine elimination reactions on model oxo surfaces. AB - The synthesis and the spectroscopic and structural characterization of lower-rim silylated and rare-earth-metalated calix[4]arenes are presented. Hexamethyldisilazane, HN(SiMe3)2, reacted in a selective manner with [p-tert buttylcalix[4]arene]H4 (1) in refluxing mesitylene to give the 1,3-silylated product [p-tert-butylcalix[4]arene(SiMe3)2]H2 (2) in high yield. The molecular structure of compound 2, as revealed by X-ray crystallography, shows the pinched cone conformation of the calixarene bowl, featuring hydrogen bonding between the phenylsilyl ether and phenolic oxygen atoms (O...O, 2.838 A). From the reaction of the sterically more crowded tetraphenyldimethyldisilazane, HN(SiMePh2)2, only starting material could be recovered. In contrast, tetramethyldisilazane, HN(SiHMe2)2, afforded the tetrakis-silylated product [p-tert butylcalix[4]arene(SiHMe2)4] (3) in hexane solution at ambient temperature. A single-crystal X-ray diffraction study of compound 3 established the 1,2 alternate conformation, which is also present in solution, as indicated by 1H NMR spectroscopy. The yttrium complex Y[N(SiHMe2)2]3(THF)2 (4) exchanged all of its silylamide ligands when treated with an equimolar amount of 1 in toluene at ambient temperature to yield compound 5, as indicated by IR and NMR spectroscopy. The molecular structure of 5 revealed a centrosymmetric dimer of composition [Y(p tert-butylcalix[4]arene(SiHMe2)(THF)]2. Three of the deprotonated phenolic oxygen atoms of the calixarene bowl bind to the metal center, two as terminal ligands and one in a bridging mode, while the fourth undergoes in situ silylation (nu(SiH) 2127 cm-1). The distorted-trigonal-bipyramidal coordination geometry is completed by a THF molecule. Bis-silylated 2 reacted with 4 to form the heteroleptic complex (Y[p-tert-butylcalix[4]arene(SiMe3)2][N(SiHMe2)2]) (6). Crystal data: C50H72O4Si2 (2), triclinic, P1, a = 12.8914(3) A, b = 14.9270(5) A, c = 15.1652(4) A, alpha = 77.293(2) degrees, beta = 65.019(2) degrees, gamma = 72.234(2) degrees, Z = 2; C52H80O4Si4 (3), triclinic, P1, a = 10.1774(2) A, b = 14.1680(2) A, c = 18.7206(2) A, alpha = 95.8195(8) degrees, beta = 95.5294(8) degrees, gamma = 98.1098(7) degrees, Z = 2; C100H132O10Si2Y2, 2(C6H6) (5), triclinic, P1, a = 13.2625(4) A, b = 14.5894(3) A, c = 17.0458(5) A, alpha = 65.0986(14) degrees, beta = 77.8786(8) degrees, gamma = 85.5125(13) degrees, Z = 1. PMID- 11196945 TI - Polyhedral members of the Mg2nP2m family derived from dimeric magnesium trialkylsilylphosphandiide. AB - The magnesiation of tri(tert-butyl)silylphosphane in THF yields tetrameric (tetrahydrofuran-O)magnesium tri(tert-butyl)silylphosphandiide 1. The central moiety is a slightly distorted Mg4P4 cube with tetracoordinate magnesium and phosphorus atoms. The reaction of dibutylmagnesium with H2PSitBu3 in toluene gives tetramagnesium tetrakis[mu-tri(tert-butyl)silylphosphanide] bis[mu 4 tri(tert-butyl)silylphosphandiide] 2. The central fragment is a Mg4P2 octahedron with the phosphorus atoms in a trans position. The Mg...Mg edges are bridged by the phosphanide substituents. Crystallographic data of 1: C68H148Mg4O5P4Si4, monoclinic, P2(1)/c, a = 13.454(1) A, b = 26.123(1) A, c = 24.539(2) A, beta = 96.53(1) degrees, Z = 4; crystallographic data of 2: C72H166Mg4P6Si6, monoclinic, P2(1)/n, a = 13.951(1) A, b = 14.269(1) A, c = 24.209(2) A, beta = 102.415(1) degrees, Z = 2. PMID- 11196946 TI - Matrix-isolated Al2OF6(2-) ion in molten and solid LiF/NaF/KF. AB - A Raman spectrum consistent with that expected from an Al2OF6(2-) ion was observed when Na2O was dissolved in a eutectic LiF/NaF/KF (FLINAK) melt at 500 degrees C, which contained a low concentration of either AlF3 or Na3AlF6. Furthermore, it was possible to trap the Al2OF6(2-) ion in the frozen solid and to measure its Raman and IR spectra at 25 degrees C. A number of bands have been detected; among those, the two most characteristic bands of the Al2OF6(2-) ion at 494 (polarized) and 265 cm-1 in the FLINAK melt at 500 degrees C, and those at 509 and 268 (Raman) and approximately 780 to approximately 900 (IR) cm-1 for the compound matrix isolated in solid FLINAK at 25 degrees C. In the absence of added oxide, the dissolved aluminum fluoride was in the form of the octahedral AlF6(3-) ion, which has characteristic Raman bands at 542 and 325 cm-1 in the FLINAK melt at 500 degrees C. Whereas alumina, Al2O3, was found to be essentially insoluble in FLINAK melts, it was possible to dissolve sufficient amounts of Na2O to convert most of the AlF6(3-) to the oxyfluoroaluminate, Al2OF6(2-). These solutions appeared to be metastable with respect to formation of insoluble alumina at higher temperatures. The present results can be compared to previous measurements on alumina dissolved in pure molten cryolite at much higher temperatures, where alumina solubility is low and broad bands due to oxide species are difficult to detect due to overlap with bands from AlF6(3-) and AlF4 . PMID- 11196947 TI - Crucial role of Cu-S bonding for structural changes accompanying the reversible CuI/CuII transition in an unrestrained Cu(N[symbol: see text]S)2 coordination arrangement. An experimental and DFT study. AB - The structure of reversibly oxidizable [Cu(mmb)2](BF4) with 1-methyl-2 (methylthiomethyl)-1H-benzimidazole (mmb) as bidentate N,S-donor ligand has been determined and compared with that of the copper(II) species [Cu(mmb)2(eta 1 ClO4)](ClO4). In the complex ions of the equilibrium [CuI(mmb)2](+) + ClO4- reversible e- + [CuII(mmb)2-(eta 1-ClO4)]+ the almost linear N-Cu-N backbone is invariant whereas the bonds to the thioether sulfur centers and especially the changing S-Cu-S angle (145.18(5) degrees for the CuII species, 109.33(3) degrees for the CuI form) reflect the metal oxidation state. In contrast to the perchlorate coordinating copper(II) species, [CuI(mmb)2](BF4) contains a cation with a very large vacant site at the metal center, resulting in elliptical channels within the crystal. DFT calculations on [CuI(mb)2]+, [CuII(mb)2]2+, and [CuII(mb)2(OClO3)]+ with mb = 2-methylthiomethyl-1H-benzimidazole confirm the essential role of the metal-sulfur bonds in responding to the reversible CuI/II electron transfer process, even in the absence of electronically stronger interacting thiolate sulfur centers or sophisticated oligodentate ligands. PMID- 11196948 TI - Organic-inorganic hybrids based on polyoxometalates. 6. Syntheses, structure, and reactivity of the bis(tert-butylsilyl)decatungstophosphate [(gamma-PW10O36)(t BuSiOH)2]3-. AB - Bis(tert-butylsilyl)decatungstophosphate (n-Bu4N)3[(gamma-PW10O36)(t-BuSiOH)2] (1) has been synthesized through phase-transfer conditions, by reaction of t BuSiCl3 with Cs7[(gamma-PW10O36)].xH2O. This new hybrid anion has been characterized by elemental analysis, X-ray crystallography, multinuclear solution and solid-state NMR, and infrared spectroscopy. Crystals of 1 are monoclinic, space group C2/c, with lattice constants a = 44.762(10) A, b = 19.032(4) A, c = 22.079(8) A, beta = 98.9(2) degrees, and Z = 8. Anion 1 has nominal Cs symmetry and displays an "open structure" with two t-BuSiOH groups anchored to the (gamma PW10O36) framework. The two t-BuSiOH units are nonequivalent as confirmed by 29Si CP-MAS NMR and by diffuse reflection infrared spectroscopy. The two OH groups are linked through one H-bond (dO-O = 2.63 A). According to 29Si and 183W NMR, 1 adopts a more symmetrical conformation (C2v) in solution. Anion 1 reacts cleanly in homogeneous conditions with Me2SiCl2 to yield (n-Bu4N)3[(gamma-PW10O36)(t BuSiO)2(SiMe2)] (2). The structure of 2 has been inferred from multinuclear NMR and infrared spectroscopy. The hybrid "closed-structure" anion 2 consists of the (gamma-PW10O36) framework on which is grafted a heterosilylated network composed of a capping fragment, Si(CH3)2, linked to the t-BuSi groups through two siloxane bridges. PMID- 11196949 TI - Synthesis and structural characterization of Sm(II) and Yb(II) complexes containing sterically demanding, chelating secondary phosphide ligands. AB - Metathesis between [(Me3Si)2CH)(C6H4-2-OMe)P]K and SmI2(THF)2 in THF yields [([Me3Si]2CH)(C6H4-2-OMe)P)2Sm(DME)(THF)] (1), after recrystallization. A similar reaction between [(Me3Si)2CH)(C6H3-2-OMe-3-Me)P]K and SmI2(THF)2 yields [([Me3Si]2CH)(C6H3-2-OMe-3-Me)P)2Sm(DME)].Et2O (2), while reaction between [(Me3Si)2CH)(C6H4-2-CH2NMe2)P]K and either SmI2(THF)2 or YbI2 yields the five coordinate complex [([Me3Si]2CH)(C6H4-2-CH2NMe2)P)2Sm(THF)] (3) or the solvent free complex [([Me3Si]2CH)(C6H4-2-CH2NMe2)P)2Yb] (4), respectively. X-ray crystallography shows that complex 2 adopts a distorted cis octahedral geometry, while complex 1 adopts a distorted pentagonal bipyramidal geometry (1, triclinic, P1, a = 11.0625(9) A, b = 15.924(6) A, c = 17.2104(14) A, alpha = 72.327(2) degrees, beta = 83.934(2) degrees, gamma = 79.556(2) degrees, Z = 2; 2, monoclinic, P2(1), a = 13.176(4) A, b = 13.080(4) A, c = 14.546(4) A, beta = 95.363(6) degrees, Z = 2). Complex 3 crystallizes as monomers with a square pyramidal geometry at Sm and exhibits short contacts between Sm and the ipso carbon atoms of the ligands (3, monoclinic, C2/c, a = 14.9880(17) A, b = 13.0528(15) A, c = 24.330(3) A, beta = 104.507(2) degrees, Z = 4). Whereas preliminary X-ray crystallographic data for 4 indicate a monomeric structure in the solid state, variable-temperature 1H, 13C(1H), 31P(1H), and 171Yb NMR spectroscopies suggest that 4 undergoes an unusual dynamic process in solution, which is ascribed to a monomer-dimer equilibrium in which exchange of the bridging and terminal phosphide groups may be frozen out at low temperature. PMID- 11196950 TI - Role of cyclometalation in controlling the rates of ligand substitution at platinum(II) complexes. AB - The rates of chloride for triphenylphosphine substitution have been measured in dichloromethane for a series of cyclometalated [Pt(N-N-C)Cl] complexes containing a number of terdentate N-N-C anionic ligands, derived from deprotonated alkyl-, phenyl-, and benzyl-6-substituted 2,2'-bipyridines. These rates have been compared with those of the corresponding [Pt(N-N)(C)Cl] (N-N = 2,2'-bipyridine; C = CH3 or C6H5) complexes having the same set of donor atoms but less constrained arrangements of the ligands. The reactions of the cyclometalated compounds occur as a single-stage conversion from the substrate to the ionic pair [Pt(N-N C)(PPh3)]Cl products. There is no evidence by 1H and 31P(1H) NMR spectroscopy for the formation of other Pt(II) species or of concurrent ring-opening processes. In contrast, in the monoalkyl- or monoaryl-2,2'-bipyridine complexes, chloride substitution is followed by subsequent slower processes which involve the detachment of one arm of the chelated 2,2'-bipyridine, fast cis to trans isomerization of the cis-[Pt(PPh3)2(eta 1-bipy)(R)]+ transient intermediate, and, eventually, the release of free bipy, yielding trans-[Pt(PPh3)2(R)Cl] (R = Me or Ph). All reactions are first-order with respect to complex and phosphine concentration, obeying the simple rate law kobsd = k2[PPh3]. The values of the second-order rate constant k2 do not seem particularly sensitive to the nature of the bonded organic moiety (alkyl or aryl), to its structure (cyclometalated or not), to the size of the ring, or to the number of alkyl substituents on it. The effects are those foreseen on the basis of an associative mode of activation. The only exception to this pattern of behavior is constituted by the complex [Pt(bipy phi-H)Cl] (bipy phi = 6-phenyl-2,2'-bipyridine), which features a significant rate enhancement with respect to the analogue [Pt(bipy)(Ph)Cl] complex. The results of this work, together with those of a previous paper, suggest that there is not a specific role of cyclometalation in controlling the reactivity, unless an in-plane aryl ring becomes part of the pi-acceptor system of the chelated 2,2 bipyridine, behaving as a cyclometalated analogue of the nitrogen terdentate 2,2':6',2"-terpyridine. PMID- 11196951 TI - Covalent metal-organic networks: pyridines induce 2-dimensional oligomerization of (mu-OC6H4O)2Mpy2 (M = Ti, V, Zr). AB - Treatment of M(OiPr)4 (M = Ti, V) and [Zr(OEt)4]4 with excess 1,4-HOC6H4OH in THF afforded [M(OC6H4O)a(OC6H4OH)3.34-1.83a(OiPr)0.66-0.17a(THF)0.2]n (M = Ti, 1-Ti; V, 1-V, 0.91 < or = a < or = 1.82) and [Zr(1,4-OC6H4O)2-x(OEt)2x]n (1-Zr, x = 0.9). The combination of of 1-M (M = Ti, V, Zr) or M(OiPr)4 (M = Ti, V), excess 1,4- or 1,3-HOC6H4OH, and pyridine or 4-phenylpyridine at 100 degrees C for 1 d to 2 weeks afforded various 2-dimensional covalent metal-organic networks: [cis M(mu 1,4-OC6H4O)2py2] infinity (2-M, M = Ti, Zr), [trans-M(mu 1,4-OC6H4O)2py2.py] infinity (3-M, M = Ti, V), solid solutions [trans-TixV1-x(mu 1,4-OC6H4O)2py2.py] infinity (3-TixV1-x, x approximately 0.4, 0.6, 0.9), [trans-M(mu 1,4-OC6H4O)2(4 Ph-py)2] infinity (4-M, M = Ti, V), [trans-Ti(mu 1,3-OC6H4O)2py2] infinity (5 Ti), and [trans-Ti(mu 1,3-OC6H4O)2(4-Ph-py)2] infinity (6-Ti). Single-crystal X ray diffraction experiments confirmed the pleated sheet structure of 2-Ti, the flat sheet structure of 3-Ti, and the rippled sheet structures of 4-Ti, 5-Ti, and 6-Ti. Through protolytic quenching studies and by correspondence of powder XRD patterns with known titanium species, the remaining complexes were structurally assigned. With py or 4-Ph-py present, aggregation of titanium centers is disrupted, relegating the building block to the cis- or trans-(ArO)4Tipy2 core. The sheet structure types are determined by the size of the metal and the interpenetration of the layers, which occurs primarily through the pyridine residues and inhibits intercalation chemistry. PMID- 11196952 TI - Crystal structure of (difluoro)methoxyoxo iodine(V) IF2(O)OCH3. AB - (Difluoro)methoxyoxo iodine(V) (IF2(O)OCH3), the methyl ester of the unknown difluoro iodic acid (IF2(O)OH), was obtained by the reaction of methoxytrimethyl silane with iodine pentafluoride. IF2(O)OCH3 crystallizes orthorhombic in the space group Pbca with a = 7.605(1) A, b = 7.360(1) A, c = 15.017(1) A, and eight formula units per unit cell. The final R indices [I > 2 sigma(I)] are R1 = 0.0264 and wR2 = 0.0516. Additionally, IF2(O)OCH3 was characterized by its vibrational spectra and quantum mechanical calculations were performed. PMID- 11196953 TI - Kinetic origin of the chelate effect. Base hydrolysis, H-exchange reactivity, and structures of syn,anti-[Co(cyclen)(NH3)2]3+ and syn,anti-[Co(cyclen)(diamine)]3+ ions (diamine = H2N(CH2)2NH2, H2N(CH2)3NH2). AB - The synthesis of syn,anti-[Co(cyclen)en](ClO4)3 (1(ClO4)3) and syn,anti [Co(cyclen)tn](ClO4)3 (2(ClO4)3) is reported, as are single-crystal X-ray structures for syn,anti-[Co(cyclen)(NH3)2](ClO4)3 (3(ClO4)3). 3(ClO4)3: orthorhombic, Pnma, a = 17.805(4) A, b = 12.123(3) A, c = 9.493(2) A, alpha = beta = gamma = 90 degrees, Z = 4, R1 = 0.030. 1(ClO4)3: monoclinic, P2(1)/n, a = 8.892(2) A, b = 15.285(3) A, c = 15.466(3) A, alpha = 90 degrees, beta = 91.05(3) degrees, gamma = 90 degrees, Z = 4, R1 = 0.0657. 2Br3: orthorhombic, Pca2(1) a = 14.170(4) A, b = 10.623(3) A, c = 12.362(4) A, alpha = beta = gamma = 90 degrees, Z = 4, R1 = 0.0289. Rate constants for H/D exchange (D2O, I = 1.0 M, NaClO4, 25 degrees C) of the syn and anti NH protons (rate law: kobs = ko + kH[OD-]) and the apical NH, and the NH3 and NH2 protons (rate law: kobs = kH[OD-]) in the 1, 2, and 3 cations are reported. Deprotonation constants (K = [Co(cyclen H)(diamine)2+]/[Co(cyclen)(diamine)3+][OH-]) were determined for 1 (5.5 +/- 0.5 M 1) and 2 (28 +/- 3 M-1). In alkaline solution 1, 2, and 3 hydrolyze to [Co(cyclen)(OH)2]+ via [Co(cyclen)(amine)OH)]2+ monodentates. Hydrolysis of 3 is two step: kobs(1) = kOH(1)[OH-], kobs(2) = ko + kOH(2)[OH-] (kOH(1) = (2.2 +/- 0.4) x 10(4) M-1 s-1, ko = (5.1 +/- 1.2) x 10(-4) s-1, kOH(2) = 1.0 +/- 0.1 M-1 s 1). Hydrolysis of 2 is biphasic: kobs(1) = k1K[OH-]/(1 + K[OH-] (k1 = 5.0 +/- 0.2 s-1, K = 28 M-1), kobs(2) = k2K2[OH-]/(1 + K2[OH-]) (k2 = 3.5 +/- 1.2 s-1, K2 = 1.2 +/- 0.8 M-1). Hydrolysis of 1 is monophasic: kobs = k1k2KK2[OH-]2/(1 + K[OH 1])(k-1 + k2K2[OH-]) (k1 = 0.035 +/- 0.004 s-1, k-1 = 2.9 +/- 0.6 s-1, K = 5.5 M 1, k2K2 = 4.0 M-1 s-1). The much slower rate of chelate ring-opening in 1, compared to loss of NH3 from 3, is rationalized in terms of a reduced ability of the former system to allow the bond angle expansion required to produce the SN1CB trigonal bipyramidal intermediate. PMID- 11196954 TI - Structure and bonding of transition metal-boryl compounds. Theoretical study of [(PH3)2(CO)ClOs-BR2] and [(PH3)2(CO)2ClOs-BR2] (BR2 = BH2, BF2, B(OH)2, B(OCH=CHO), Bcat). AB - Quantum chemical DFT calculations using the B3LYP functionals have been carried out for the electronically unsaturated 16 VE five-coordinate osmium boryl complexes [(PH3)2(CO)ClOs-BR2] and the 18 VE six-coordinate complexes [(PH3)2(CO)2ClOs-BR2] with BR2 = BH2, BF2, B(OH)2, B(OHC=CHO), and Bcat (cat = catecholate O2C6H4). The bonding situation of the Os-BR2 bond was analyzed with the help of the NBO partitioning scheme. The Os-B bond dissociation energies of the 16 VE complexes are very high, and they do not change very much for the different boryl ligands. The 18 VE complexes have only slightly lower bond energies than the 16 VE species. The Os-B bond in both classes of compounds is provided by a covalent sigma-bond which is polarized toward osmium and by strong charge attraction. Os-->B pi-donation is not important for the Os-B binding interactions, except for the Os-BH2 complexes. The stability of the boryl complexes [Os]-BR2 comes mainly from B<--R pi-donation, which is clearly higher than the Os-->B pi-donation. The intraligand charge distribution of the BR2 group changes little when the Os-B bond is formed, except for BH2. The CO ligand in [(PH3)2(CO)2ClOs-BR2] which is trans to BR2 has a relatively weak bond to the osmium atom. PMID- 11196955 TI - Experimental and theoretical studies of the d8-d10 interaction between Pd(II) and Au(I): bis(chloro[(phenylthiomethyl)diphenylphosphine]gold(I))- dichloropalladium(II) and related systems. AB - The reaction between thioether phosphine gold(I) precursors such as [AuCl(Ph2PCH2SPh)], 1, or [Au(Ph2PCH2SPh)2]CF3SO3 and PdCl2(NCPh)2 affords the new compounds [(AuCl(Ph2PCH2SPh)2PdCl2], 2, and [AuPdCl2(Ph2PCH2SPh)2]CF3SO3, 3. The crystal structure of complex 2 has the sterically unhindered Pd(II) and Au(I) at a distance of 314 pm. Quasirelativistic pseudopotential calculations on [AuPdCl3(PH2CH2SH)(SH2)] models give short Au-Pd distances at the second-order Moller-Plesset (MP2) level and long Au-Pd distances at Hartree-Fock (HF) level. A detailed analysis of the Au-Pd interaction shows dominant dispersion, some ionic contributions, and no net charge transfer between the metals. PMID- 11196956 TI - Structural characterization and formation mechanism of sitting-atop (SAT) complexes of 5,10,15,20-tetraphenylporphyrin with divalent metal ions. Structure of the Cu(II)-SAT complex as determined by fluorescent extended X-ray absorption fine structure. AB - The UV-vis absorption spectra and the formation kinetics of sitting-atop (SAT) complexes (M(H2tpp)2+) of 5,10,15,20-tetraphenylporphyrin (H2tpp) with a series of divalent metal ions (M2+ = Mn2+, Fe2+, Co2+, Ni2+, Cu2+, and Zn2+) in acetonitrile have been investigated. The structural characteristics of the SAT complexes for a series of M2+ ions are discussed on the basis of the UV-vis absorption spectra. The structure parameters around Cu2+ in the Cu(II)-SAT complex were determined by a fluorescent EXAFS method: the coordination number is 6 with three kinds of Cu-N interactions having bond lengths of 2.05, 1.98, and 2.32 A for pyrrolenine nitrogens of H2tpp, acetonitrile nitrogens at equatorial sites, and acetonitrile nitrogens at axial sites, respectively. The rate constants at 25 degrees C for the formation of the SAT complex in acetonitrile are as follows: kf/mol-1 kg s-1 = 3.4 x 10(2) for Mn2+, 0.18 for Co2+, 1.6 x 10( 3) for Ni2+, and 61 for Zn2+. The finding that the variation trends in the rate constants for a series of M2+ ions for the SAT complex formation and the solvent exchange reaction in various solvents are very similar indicates that the rate determining step for the SAT complex formation is the interchange between the coordinating nitrogen of a bound acetonitrile and the pyrrolenine nitrogen of H2tpp. The fact that the values of kf are smaller by 4-6 orders of magnitude in comparison with those of the solvent exchange suggests that there is a large energetic loss due to the fast preequilibria prior to the rate-determining step, such as deformation of a porphyrin ring and outer-sphere encounter formation due to an electrostatic interaction between M2+ and the local negative charge on the pyrrolenine nitrogens. We observed the subsequent formation of the corresponding metalloporphyrins by deprotonation of the SAT complex and oxidation of the M2+ center, of which the dynamic behavior was significantly different for the different M2+ ions. PMID- 11196957 TI - Ion-pair interactions of lanthanide(III) complexes in aqueous solutions. AB - The formation of ion-pair adducts between the cationic complex La(THP)3+ (THP = 1,4,7,10-tetrakis(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane) and the anionic complexes Tm(DOTA)- (DOTA = 1,4,7,10-tetraazacyclododecane-N,N',N",N"' tetraacetate), Tm(DTPA)2- (DTPA = diethylenetriamine-N,N,N',N",N"-pentaacetate), Tm(TTHA)3- (TTHA = triethylenetetraamine-N,N,N',N",N"',N"'-hexaacetate), and Tm(DOTP)5- (DOTP = 1,4,7,10-tetraazacyclododecane-N,N',N",N"' tetrakis(methylenephosphonate)) is examined by 13C NMR spectroscopy. The induced 13C shifts of the La(THP)3+ complex are followed by titration of the Tm(III) complexes of DOTA, DTPA, and TTHA at pH 7. From these data, the stability constants are calculated to be beta 1 = 64 M-1 (1:1), beta 1 = 296 M-1 (1:1), and beta 2 = 26,000 M-2 (2:1) for the ion pairs of La(THP)3+, with Tm(DOTA)-, Tm(DTPA)2-, and Tm(TTHA)3-, respectively. The La(THP)3+,Tm(DOTP)5- system elicits chiral resolution of the rapidly interconverting Tm(DOTP)5- isomers. PMID- 11196958 TI - Kinetics and mechanism of oxygen transfer to methyloxo(dithiolato)rhenium(V) complexes. AB - The kinetics and mechanism of the reactions of the dimeric and monomeric methyloxo(dithiolato)rhenium(V) complexes [(o-SC6H4CH2S)Re(O)CH3]2 and [(o SC6H4CH2S)PyRe(O)CH3] (Py = pyridine) with XO, sulfoxides, and pyridine N-oxides are studied. In these reactions, an oxygen atom from XO is transferred to rhenium, from which it later removed. A reaction scheme is proposed to interpret the kinetic data. This scheme features the formation of a monomeric (sulfoxide)- or (pyridine N-oxide)(dithiolato)methyloxorhenium(V) complex followed by its bimolecular oxidation in a rate-controlling step. Several sulfoxides (methyl, methyl phenyl, and substituted diphenyl) all react at similar rates. Activation parameters are determined for dimethyl sulfoxide and di-4-tolyl sulfoxide from temperature-dependent studies. The reactions with pyridine N-oxides show autocatalysis in which the catalyst is confirmed to be pyridine formed in the reactions. PMID- 11196959 TI - Preparation and properties of cyclopentadienyl- and pentamethylcyclopentadienyl titanium(IV) complexes with the C8H4S8 ligand, electrical conductivities of their oxidized species, and X-ray crystal structure of Ti(C5Me5)2(C8H4S8). AB - Ti(C5H5)2(C8H4S8) (1), Ti(C5Me5)2(C8H4S8) (2), [NMe4][Ti(C5H5)(C8H4S8)2] (3), and [NMe4][Ti(C5Me5)(C8H4S8)2] (4) [C8H4S8(2-) = 2-(4,5-ethylenedithio)-1,3-dithiole 2-ylidene)-1,3-dithiole-4,5- dithiolate(2-)] were prepared by reaction of Ti(C5H5)2Cl2, Ti(C5Me5)2Cl2, Ti(C5H5)Cl3, or Ti(C5Me5)Cl3 with Li2C8H4S8 or [NMe4]2[C8H4S8] in THF. They were oxidized by iodine, the ferrocenium cation, or TCNQ (7,7,8,8-tetracyano-p-quinodimethane) in CH2Cl2 or in acetone to afford one electron-oxidized and over-one-electron-oxidized species, [Ti(C5H5)2(C8H4S8)].I3, [Ti(C5H5)2(C8H4S8)][PF6], [Ti(C5Me5)2(C8H4S8)].I3, [Ti(C5Me5)2(C8H4S8)][PF6], [Ti(C5H5)(C8H4S8)2].I0.9, [Ti(C5H5)(C8H4S8)2][TCNQ]0.3, [Ti(C5Me5)(C8H4S8)2].I2.4, and [Ti(C5Me5)(C8H4S8)2][TCNQ]0.3, with the C8H4S8 ligand-centered oxidation. They exhibited electrical conductivities of 1.6 x 10( 1) to 7.6 x 10(-4) S cm-1 measured for compacted pellets at room temperature. The crystal structure of 2 was clarified to consist of isolated dimerized units of the molecules through some sulfur-sulfur nonbonded contacts: monoclinic, P2(1)/c, a = 9.534(2) A, b = 18.227(2) A, c = 17.775(2) A, beta = 94.39(1) degrees, Z = 4. PMID- 11196960 TI - Unprecedented stabilization of cobalt(II) in a tetrahedral S2O2 environment: the use of a redox-noninnocent ligand. AB - The reaction of Zn(II) and Co(II) with thiosalicylic acid, o-HSC6H4COOH, and its methyl ester has led to the following complexes: [Zn(SC6H4COO)] (1), (NEt4)Na[Zn(SC6H4COO)2].H2O (2), (NEt4)2Na[Co(SC6H4COO)3].2H2O (3), (NEt4)3Na3[(Co(SC6H4COO)3)2].6MeOH (4), [Zn(SC6H4COOMe)2] (5), and [Co(SC6H4COOMe)n], n = 2 (6), 3 (7). These ligands have not allowed stabilization of Co(II) in a sulfur-oxygen coordination environment. The structures of complexes 2-4 and 7 have been determined crystallographically. Those of 2-4 show significant similarities such as the behavior of the -SC6H4COO- anion as chelating ligand and the involvement of sodium ions as a structural element. Thus, the structure of the [Na(Zn(SC6H4COO)2)(H2O)]- anion in complex 2 can be described as infinite chains of consecutive [Zn(SC6H4COO)2]2- metalloligands linked by [Na(H2O)]+ centers, that of the [Na(Co(SC6H4COO)3(H2O)2)]2(4-) anion in 3 as a centrosymmetric tetranuclear Co2Na2 dimer with a (CoIII(S[symbol: see text]O)3)Na(mu-H2O)2Na(CoIII(S[symbol: see text]O)3) core, and that of the pentanuclear [Na3(Co(SC6H4COO)3)2(MeOH)6]3- anion in 4 as two dinuclear [(CoIII(S[symbol: see text]O)3)Na(MeOH)3] fragments linked to a central sodium ion, which appears to be the first structurally characterized example of a NaS6 site. The use of the o-HSC6H4COOMe ligand allowed the synthesis of [Co(SC6H4COOMe)2] (6) but not its full structural characterization. Instead, [Co(SC6H4COOMe)3] (7) was obtained and structurally characterized. It consists of mononuclear molecules containing an octahedral CoIIIS3O3 core. The selection of 2,2-diphenyl-2-mercaptoacetic acid as ligand with reductive properties has afforded the first mononuclear complex containing a CoIIS2O2 core and thus an unprecedented model for Co(II)-substituted metalloproteins containing tetrahedral MS2O2 active sites. The synthesis and full structural characterization of the isostructural complexes (NEt4)2[Zn(Ph2C(S)COO)2] (8) and (NEt4)2[Co(Ph2C(S)COO)2] (9) show that they consist of discrete [M(Ph2C(S)COO)2]2- anions, with a distorted tetrahedral coordination about the metal. In addition, the stability conferred by the ligand on the CoIIS2O2 core has allowed its characterization in solution by paramagnetic 1D and 2D 1H NMR studies. The longitudinal relaxation times of the hyperfine-shifted resonances and NOESY spectra have led to the assignment of all resonances of the cobalt complex and confirmed that it maintains its tetrahedral geometry in solution. Magnetic measurements (2-300 K) for complex 9 and 9.2H2O are in good agreement with distorted tetrahedral and octahedral environments, respectively. PMID- 11196961 TI - ((Fluoroformyl)imido)(trifluoromethyl)sulfur fluoride, FC(O)N = S(F)CF3: unexpected conformational properties. AB - The geometric structure and conformational properties of ((fluoroformyl)imido)(trifluoromethyl)sulfur fluoride, FC(O)N = S(F)CF3, are investigated by gas electron diffraction (GED) experiments, IR (gas) spectroscopy, and quantum chemical calculations (HF, MP2, and B3LYP with 6-31G* basis sets). The GED intensities are reproduced best with a mixture of 79(12)% trans-syn and 21(12)% cis-syn conformers. "Trans/cis" describes the orientation around the S=N double bond (FC(O) group relative to sulfur substituents), and "syn" refers to the orientation of the C=O bond relative to the S=N bond. From the intensities of the C=O bands in the IR (gas) spectrum, a composition of 86(8)%:14(8)% is derived. These ratios correspond to delta G0(GED) = 0.79(36) and delta G0(IR) = 1.09(35) kcal mol-1. The preference of a trans structure, around the S=N double bond is unexpected, since all imidosulfur compounds studied thus far possess a cis configuration. The conformational properties are reproduced qualitatively correctly by all theoretical calculations. The predicted energy differences delta E(HF) = 2.41, delta E(MP2) = 0.64, and delta E(B3LYP) = 0.28 kcal mol-1 are larger or slightly smaller than the experimental values. Additional theoretical calculations (B3LYP) for several imidosulfur compounds reveal that only FC(O)N=S(F)CF3, with mixed substitution at sulfur and the FC(O) group bonded to nitrogen, prefers the trans structure. PMID- 11196962 TI - Reaction of (carbonylimido)sulfur(IV) derivatives with TAS-fluoride, (Me2N)3S+Me3SiF2-. AB - In the reaction of TAS-fluoride, (Me2N)3S+Me3SiF2-, with carbonyl sulfur difluoride imides RC(O)NSF2 (R = F, CF3), C-N bond, cleavage is observed, and TAS+RC(O)F2- and NSF are the final products. From TASF and RC(O)NS(CF3)F, the salts TAS+RC(O)NS(CF3)F2- (R = F (14), CF3 (15)), with psi-pentacoordinate sulfur centers in the anions, are formed. An X-ray structure investigation of 14 shows that the fluorine atoms occupy axial positions and CF3, NC(O)F, and the sulfur lone pair occupy equatorial positions of the trigonal bipyramid. The -C(O)F group lies in the equatorial plane with the CO bond synperiplanar to the SN bond. According to B3LYP calculations, this structure corresponds to a global minimum and the expected axial orientation of the -C(O)F group represents a transition state. Calculations for the unstable FC(O)NSF3- anion show a different geometry. The -C(O)F group deviates 40 degrees from axial orientation, and the equatorially bonded fluorine is, in contrast to the -CF3 group in 14, syn positioned. PMID- 11196963 TI - Formation of mono-, bi-, tri-, and tetranuclear Ag(I) complexes of C3-symmetric tripodal benzimidazole ligands. AB - The C3-symmetric tripodal ligand tris(2-benzimidazolylmethyl)amine (ntb) and its alkyl-substituted derivatives tris(N-R-benzimidazol-2-ylmethyl)amine (R = methyl, Mentb; R = ethyl, Etntb; R = propyl, Prntb) react with various silver(I) salts to afford mononuclear [Ag(Prntb)(CF3SO3)].0.25H2O, 1, binuclear [Ag2(Mentb)2](CF3SO3)2.H2O, 2, trinuclear [Ag3(Etntb)2](ClO4)3.CH3OH, 3, and tetranuclear [Ag4(ntb)2(CH3CN)2(CF3CO2)2](CF3CO2)2.2H2O, 4. All four complexes have been characterized by elemental analyses, IR spectroscopy, and X-ray crystallography. The Ag(I) ion in 1 is coordinated to the three imine nitrogen atoms of the Prntb ligand and one oxygen atom of the trifluoromethanesulfonate anion in a distorted tetrahedral environment. Dinuclear 2 has C2 symmetry with each Ag(I) atom trigonally coordinated by two arms of one Mentb and one arm of another. Trinuclear 3 has C3 symmetry with a Ag3 regular triangle sandwiched between a pair of Etntb ligands such that one arm of each ligand is involved in linear coordination about an Ag(I) atom. In the tetranuclear complex 4, two linearly coordinated Ag(I) atoms lying on the molecular C2 axis are bridged by a pair of ntb ligands and the remaining pendant arm of each ntb ligand is attached to another Ag(I) atom whose tetrahedral coordination sphere is completed by an acetonitrile molecule and a chelating trifluoroacetate anion. Complexes 2 and 3 may be regarded as an aggregation of two tridentate ligands by a silver dimer and a trinuclear cluster with weak Ag...Ag interactions, respectively, while in 4 the aggregation of two tripodal ligands by four Ag(I) ions affords a multicomponent internal cavity. The packing modes of complexes 1-3 are dominated by weak supramolecular pi...pi and CH...pi interactions. Hexagonal or square channels are generated in 1 and 2, and a honeycomb layer structure is formed in 3 with solvate molecules and counteranions occupying the voids. The crystal structure of 4 consists of a three-dimensional network consolidated by NH...O and OH...O hydrogen bonds. PMID- 11196964 TI - Structure and photochemistry of dicyanocobalt(III) tetraphenylporphyrin. Photochromic reaction caused by photodissociation of axial ligand. AB - Chlorocobalt(III) tetraphenylporphyrin, (Cl)CoIIITPP, reacts with potassium cyanide in dichloromethane or benzene containing 18-crown-6 to give a green solution of [crown-K+][(CN)2CoIIITPP-]. The molecular structure of [crown K+][(CN)2CoIIITPP-] is identified by X-ray crystallography. In methanol, (Cl)CoIIITPP plus KCN also gives a green solution of [(CN)2CoIIITPP-]. The green methanol solution containing 1.4 x 10(-4) M KCN turns orange by continuous photolysis with a 250-W mercury lamp for 5 min. The orange solution returns to green when it is kept in the dark for 5 min. The kinetic study suggests that [(CN)2CoIIITPP-] dissociates CN- by continuous photolysis, giving rise to the formation of the orange species, (CH3OH)(CN)CoIIITPP. The photoproduct, (CH3OH)(CN)CoIIITPP, regenerates the green species, [(CN)2CoIIITPP-], by reaction with CN-. The laser photolysis study of [(CN)2CoIIITPP-] in methanol demonstrates that photodissociation of CN- takes place within 20 ns after the 355-nm laser pulse, resulting in the formation of two transients, I (short-lived) and II (long lived). The absorption spectra of both transients are similar to that of (CH3OH)(CN)CoIIITPP. These transients eventually return to [(CN)2CoIIITPP-]. The decay of species I follows first-order kinetics with a rate constant k. = 2 x 10(6) s-1, independent of the concentration of KCN. Species II is identified as (CH3OH)(CN)CoIIITPP, which is observed with the continuous photolysis of the solution. The laser photolysis of [crown-K+][(CN)2COIIITPP-] in dichloromethane gives the transient species, which goes back to the original complex according to first-order kinetics with a rate constant k = 5 x 10(6) s-1. [crown K+][(CN)2CoIIITPP-] is concluded to photodissociate the axial CN- to form [crown K+CN-][(CN)CoIIITPP] in which an oxygen atom of the crown moiety in [crown-K+CN-] is coordinated to the cobalt(III) atom of [(CN)CoIIITPP] at the axial position. The intracomplex reverse reaction of [crown-K+CN-][(CN)CoIIITPP] leads to the regeneration of [crown-K+][(CN)2CoIIITPP-]. The structure and the reaction of the transient species I observed for [(CN)2CoIIITPP-] in methanol are discussed on the basis of the laser photolysis studies of [crown-K+][(CN)2CoIIITPP-] in dichloromethane. PMID- 11196965 TI - Coordination of lanthanide triflates and perchlorates with N,N,N',N' tetramethylsuccinamide. AB - Compounds formed from the reaction of N,N,N',N'-tetramethylsuccinamide (TMSA) with trivalent lanthanide salts possessing the poorly coordinating counteranions triflate (CF3SO3-) and perchlorate (ClO4-) have been prepared and examined. Structural features of these Ln-TMSA compounds have been studied in the solid phase by thermogravimetric analysis, infrared spectroscopy, and, in selected cases, by single-crystal X-ray diffraction and in solution by infrared spectroscopy. Eight-coordinate compounds, [Ln(TMSA)4]3+, derived from coordination of four succinamide ligands to the metal ion could be formed with all lanthanides examined (Ln = La, Pr, Nd, Eu, Yb, Lu). Structural analyses by single-crystal X-ray diffraction were performed for the lanthanide triflate salts Ln(C8H16N2O2)4(CF3SO3)3: Ln = La, compound 1, monoclinic, P2(1)/n, a = 11.0952(2) A, b = 19.2672(2) A, c = 24.9759(3) A, beta = 90.637(1) degrees, Z = 4, Dcalcd = 1.586 g cm-3; Ln = Nd, compound 2, monoclinic, C2/c, a = 24.6586(10) A, b = 19.3078(7) A, c = 11.1429(4) A, beta = 90.450(1) degrees, Z = 4, Dcalcd = 1.603 g cm-3; Ln = Eu, compound 3, monoclinic, C2/c, a = 24.4934(2) A, b = 19.3702(1) A, c = 11.1542(1) A, beta = 90.229(1) degrees, Z = 4, Dcalcd = 1.617 g cm-3; Ln = Lu, compound 5, monoclinic, C2/c, a = 24.2435(4) A, b = 19.6141(2) A, c = 11.2635(1) A, beta = 90.049(1) degrees, Z = 4, Dcalcd = 1.626 g cm-3. X-ray analysis was also carried out for the perchlorate salt: Ln = Eu, compound 4, triclinic, P1, a = 10.9611(2) A, b = 14.6144(3) A, c = 15.7992(2) A, alpha = 106.594(1) degrees, beta = 91.538(1) degrees, gamma = 90.311(1) degrees, Z = 2, Dcalcd = 1.561 g cm-3. In the presence of significant amounts of water, 7 coordinate compounds with mixed aquo-TMSA cation structures [Ln(TMSA)3(H2O)]3+ (Ln = Yb) and [Ln(TMSA)2(H2O)3]3+ (Ln = La, Pr, Nd, Eu, Yb) have been isolated with structural determinations by single-crystal X-ray diffraction obtained for the following species: Yb(C8H16N2O2)3(H2O)(CF3SO3)3, compound 6, monoclinic, P2(1)/n, a = 8.9443(3) A, b = 11.1924(4) A, c = 44.2517(13) A, beta = 93.264(1) degrees, Z = 4, Dcalcd = 1.735 g cm-3; Yb(C8H16N2O2)3(H2O)(ClO4)3, compound 7, monoclinic, Cc, a = 19.2312(6) A, b = 11.1552(3) A, c = 19.8016(4) A, beta = 111.4260(1) degrees, Z = 4, Dcalcd = 1.690 g cm-3; Yb(C8H16N2O2)2(H2O)3(CF3SO3)3, compound 8, triclinic, P1, a = 8.6719(1) A, b = 12.2683(2) A, c = 19.8094(3) A, alpha = 75.815(1) degrees, beta = 86.805(1) degrees, gamma = 72.607(1) degrees, Z = 2, Dcalcd = 1.736 g cm-3. Unlike in the analogous nitrate salts, only bidentate binding of the succinamide ligand to the lanthanide metal is observed. IR spectroscopy studies in anhydrous acetonitrile suggest that the solid-state structures of these Ln-TMSA compounds are maintained in solution. PMID- 11196966 TI - Key factors determining the course of methyl iodide oxidative addition to diamidonaphthalene-bridged diiridium(I) and dirhodium(I) complexes. AB - The course of methyl iodide oxidative addition to various nucleophilic complexes, [Ir2(mu-1,8-(NH)2naphth)(CO)2(PiPr3)2] (1), [IrRh(mu-1,8 (NH)2naphth)(CO)2(PiPr3)2] (2), and [Rh2(mu-1,8-(NH)2naphth)(CO)2(PR3)2] (R = iPr, 3; Ph, 4; p-tolyl, 5; Me, 6), has been investigated. The CH3I addition to complex 1 readily affords the diiridium(II) complex [Ir2(mu-1,8 (NH)2naphth)I(CH3)(CO)2(PiPr3)2] (7), which undergoes slow rearrangement to give a thermodynamically stable stereoisomer, 8. The reaction of the Ir-Rh complex 2 gives the ionic compound [IrRh(mu-1,8-(NH)2naphth)(CH3)(CO)2(PiPr3)2]I (10). The dirhodium compounds, 3-5, undergo one-center additions to yield acyl complexes of the formula (Rh2(mu-1,8-(NH)2naphth)I(COCH3)(CO)(PR3)2] (R = iPr, 12; Ph, 13; p tolyl, 14). The structure of 12 has been determined by X-ray diffraction. Further reactions of these Rh(III)-Rh(I) acyl derivatives with CH3I are productive only for the p-tolylphosphine derivative, which affords the bis-acyl complex [Rh2(mu 1,8-(NH)2naphth)(CH3CO)2I2(P(p-tolyl)3)2] (15). The reaction of the PMe3 derivative, 6, allows the isolation of the bis-methyl complex [Rh2(mu-1,8 (NH)2naphth)(mu-I)(CH3)2(CO)2(PMe3)2]I (16a), which emanates from a double one center addition. Upon reaction with methyl triflate, the starting materials, 1, 2, 3, and 6, give the isostructural cationic methyl complexes 9, 11, 17, and 18, respectively. The behavior of these cationic methyl compounds toward CH3I, CH3OSO2CF3, and tetrabutylamonium iodide is consistent with the role of these species as intermediates in the SN2 addition of CH3I. Compounds 18 and 17 react with an excess of methyl triflate to give [Rh2(mu-1,8-(NH)2naphth)(mu OSO2CF3)(CH3)2(CO)2(PMe3)2][CF3SO3] (19) and [Rh2(mu-1,8 (NH)2naphth)(OSO2CF3)(COCH3)(CH3)(CO)(PiPr3)2][CF3SO3] (20), respectively. Upon treatment with acetonitrile, complexes 17 and 18 give the isostructural cationic acyl complexes [Rh2(mu-1,8-(NH)2naphth)(COCH3)(NCCH3)(CO)(PR3)2][CF3SO3] (R = iPr, 21; Me, 22). A kinetic study of the reaction leading to 21 shows that formation of these complexes involves a slow insertion step followed by the fast coordination of the acetonitrile. The variety of reactions found in this system can be rationalized in terms of three alternative reaction pathways, which are determined by the effectiveness of the interactions between the two metal centers of the dinuclear complex and by the steric constraints due to the phosphine ligands. PMID- 11196967 TI - Columnar mesomorphism of bi- and trinuclear Ni(II), Cu(II), and VO(II) cis enamonoketone complexes with low symmetry. AB - New enaminoketone tetradentate bi- and trinuclear complexes creating columnar mesophases are reported. Various combinations of nickel, copper, or vanadyl ions were applied as metallic centers. Because of the bowlike structure of chelating centers and the low molecular symmetry (Cs) the bivanadyl complexes form two diastereoisomers, which were separated. The superexchange coupling of the electron spins of paramagnetic centers copper-copper and vanadyl-vanadyl was found for binuclear complexes in ESR studies. PMID- 11196968 TI - Preparation and characterization of oxorhenium(V) complexes with 2,2' biimidazole: the strong affinity of coordinated biimidazole for chloride ions via N-H...Cl- hydrogen bonding. AB - N,N'-Dimethylbiimidazole and bipyridine (N-N) react with ReOCl3(OPPh3)(Me2S) to give mer-ReOCl3(N-N) compounds. Nonmethylated biimidazole forms a trans-O,O [ReOCl2(OPPh3)(biimH2)]+ cation, which is tightly associated with the Cl- counterion via N-H...Cl- hydrogen bonding. Hydrolysis of ReOCl3(biimMe2) in wet acetone (5% water) leads to the linear oxo-bridged dinuclear species [(OReCl2(biimMe2)2(mu-O)] containing chelated biimMe2. Acetone solutions containing only 1% water yield the bent oxo-bridged dinuclear species [(OReCl2)2(mu-O)(mu-biimMe2)2], where each Re center retains the ReO2Cl2N2 coordination but the biimMe2 ligands are bridging. The linear oxo-bridged [(OReCl2(biimH2)2(mu-O)] complex obtained with nonmethylated biimidazole includes two Cl- ions held via N-H...Cl- hydrogen bonds, leading to a dianionic [(OReCl2(biimH2...Cl)2(mu-O)]2- unit in the crystals of the PPh4+ salt. The compounds are characterized by IR and NMR spectroscopies, and the structures of [ReOCl2(OPPh3)(biimH2)]Cl, [(OReCl2(biimH2)2(mu-O)](PPh4Cl)(2).2H2O, and [(OReCl2)2(mu-O)(mu-biimMe2)2].acetone are determined by X-ray diffraction. PMID- 11196969 TI - Copper(II) benzoate nitroxide dimers and chains: structure and magnetic studies. AB - Copper(II) benzoate dimers and linear chains have been synthesized and exhibit very different magnetic behaviors. The benzoate dimers, 1a, show typical dimeric singlet-triplet transitions and strong antiferromagnetic coupling (JST = -206 K ( 143 cm-1); H = -2JSTSa.Sb). The bromobenzoate dimer can be converted into linear chains of hydrogen-bonded monomers, showing 1-D ferromagnetic coupling (6a, theta = +9 K). Copper(II) sites can also be bridged by nitroxide-substituted benzoates, 1b and 1c, that is, 2-(4'-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-3-oxide-1 oxyl (NNBA, 3a), with JST = -216 K (-150 cm-1), with comparable interactions between the nitroxide and triplet Cu(II) spins, theta T = -157 K. A 1-D chain similar to the bromobenzoate monomers can also be produced with NNBA, also exhibiting ferromagnetic coupling (6b, theta = +0.67 K), albeit much weaker. Other nitroxides have been introduced into the Cu(II) dimer system by capping copper(II) acetate with the polydentate 2-(4'-pyridyl)-4,4,5,5 tetramethylimidazoline-3-oxide-1-oxyl (PYNN, 3b), which exhibits almost no coupling to the copper centers when both ends of the dimer are capped (1d, theta = -5.8 K). In contrast, strong coupling is observed when only one PYNN is used (2, theta = -300 K), which is the result of direct coordination of the nitroxide to the copper centers, producing a chain of the dimer units. PMID- 11196970 TI - Oxo complexes of osmium(IV) formed via dioxygen activation. X-ray structures of [OsX(dcpe)2]PF6 (X = Cl, Br), [OsCl(eta 2-O2)(dcpe)2]BPh4, and [OsCl(O)(dcpe)2]BPh4 (dcpe = 1,2-bis(dicyclohexylphosphino)ethane). AB - Dioxygen addition to the 16-electron complexes [OsX(P-P)2]+ (3) gives the dioxygen adducts [OsCl(eta 2-O2)(P-P)2]+ (3), which in turn react with HCl gas to give the novel osmium(IV) oxo complexes trans-[OsX(O)(P-P)2]+ (5) (X = Cl, Br; P P = 1,2-bis(dicyclohexylphosphino)ethane (dcpe), 1,2-bis(diethylphosphino)ethane (depe), 1,2-bis((2R,5R)-2,5-dimethylphospholano)benzene (Me-duphos)). The complexes [OsX(dcpe)2]+ (X = Cl, Br) (3) are studied by X-ray crystallography and are shown to have a "Y-shaped" coordination geometry in the equatorial plane. The X-ray structural analysis of [OsCl(eta 2-O2)(dcpe)2]+ (4a) reveals an exceptionally short O-O bond (1.315(5) A). trans-[OsCl(O)(dcpe)2]+ (5a), the first oxo complex of osmium(IV) investigated crystallographically, exhibits a long Os-O distance of 1.834(3) A. The reactivity of 4 and 5 as oxidants is described. The dioxygen complex 4a transfers one oxygen atom to PPh3 (to give Ph3PO) or oxidizes iodide ions to triiodide ions in the presence of anhydrous HCl. In both reactions, the corresponding oxo species 5a is quantitatively formed as the only metal-containing product. Oxo complexes 5 are surprisingly stable and unreactive toward standard reducing agents such as phosphines. PMID- 11196971 TI - Copper(II) complexes of pyridyl-appended diazacycloalkanes: synthesis, characterization, and application to catalytic olefin aziridination. AB - As part of an ongoing effort to rationally design new copper catalysts for olefin aziridination, a family of copper(II) complexes derived from new tetradentate macrocyclic ligands are synthesized, characterized both in the solid state and in solution, and screened for catalytic nitrene transfer reactivity with a representative set of olefins. The pyridylmethyl-appended diazacycloalkane ligands L6(py)2, L7(py)2, and L8(py)2 are prepared by alkylation of the appropriate diazacycloalkane (piperazine, homopiperazine, or diazacyclooctane) with picolyl chloride in the presence of triethylamine. The ligands are metalated with Cu(ClO4)(2).6H2O to provide the complexes [(L6(py)2)Cu(OClO3)]ClO4 (1), [(L7(py)2)Cu(OClO3)]ClO4 (2), and [(L8(py)2)Cu](ClO4)2 (3), which, after metathesis with NH4PF6 in CH3CN, afford [(L6(py)2)Cu(CH3CN)](PF6)2 (4), [(L7(py)2)Cu(CH3CN)](PF6)2 (5), and [(L8(py)2)Cu](PF6)2 (6). All six complexes are characterized by X-ray crystallography, which reveals that complexes supported by L6(py)2 and L7(py)2 (1, 2, 4, 5) adopt square-pyramidal geometries, while complexes 3 and 6, ligated by L8(py)2 feature tetracoordinate, distorted square-planar copper ions. Tetragonal geometries in solution and d(x2 - y2), ground states are confirmed for the complexes by a combination of UV-visible and EPR spectroscopies. The divergent flexibility of the three supporting ligands influences the Cu(II)/Cu(I) redox potentials within the family, such that the complexes supported by the larger ligands L7(py)2 and L8(py)2 (5 and 6) exhibit quasi-reversible electron transfer processes (E1/2 approximately -0.2 V vs Ag/AgCl), while the complex supported by L6(py)2 (4), which imposes a rigid tetragonal geometry upon the central copper(II) ion, is irreversibly reduced in CH3CN solution. Complexes 4-6 are efficient catalysts (in 5 mol % amounts) for the aziridination of styrene with the iodinane PhINTs (in 80-90% yields vs PhINTs), while only 4 exhibits significant catalytic nitrene transfer reactivity with 1-hexene and cyclooctene. PMID- 11196972 TI - Selective tin-carbon bond cleavage reactions of trimethylstannylzirconocene dichloride with electrophiles. AB - The reaction of 5,5-bis(trimethylstannyl)cyclopentadiene with CpZrCl3 (Cp = eta 5 C5H5) affords the monostannylated metallocene complex (eta 5-Me3SnC5H4)CpZrCl2 (1), accompanied by variable amounts of (eta 5-ClMe2SnC5H4)CpZrCl2 (2). The complex (1) reacts with BCl3 or with ICl to afford 2 (Sn-CH3 cleavage), but with HCl, Cp2ZrCl2 is obtained instead (Sn-Cp cleavage). Depending on the reaction conditions, treatment of either 1 or 2 with BBr3 affords (eta 5 BrMe2SnC5H4)CpZrBr2 (3) or (eta 5-Br2MeSnC5H4)CpZrBr2 (4). The reaction of 1 with excess I2 affords the iodostannylated complex (eta 5-IMe2SnC5H4)CpZrCl2 (5). Two of the complexes (2.2C6H5CH3 and 4.THF) are crystallographically characterized. The adduct 4.THF has a distorted trigonal bipyramidal geometry about tin with a long O-Sn distance of 2.655 A. We find overall that Me3Sn substituents undergo electrophilic halodemethylation much more readily than corresponding Me3Si substituents, whereas the reactivities of the halostannylated complexes toward nucleophiles such as airborne moisture are much lower than those of their halosilylated counterparts. PMID- 11196973 TI - New inorganic/organic coordination polymers generated from bidentate Schiff-base ligands. AB - The coordination chemistry of the long conjugated bidentate Schiff-base ligands 1,4-bis(3-pyridyl)-2,3-diaza-1,3-butadiene (L1) and 2,5-bis(3-pyridyl)-3,4-diaza 2,4-hexadiene (L2) with cadmium and cobalt nitrate hydrates is investigated. Four new coordination polymers are prepared by solution reactions and fully characterized by infrared spectroscopy, elemental analysis, thermogravimetric analysis, and single-crystal X-ray diffraction. [Cd(NO3)2(L1)(1.5).0.5(L1)]n (1; monoclinic, P2(1)/c; a = 7.7729(16) A, b = 19.049(4) A, c = 17.865(4) A, beta = 93.13(3) degrees, Z = 4) is obtained by combination of L1 with Cd(NO3)(2).4H2O in a benzene/methanol or THF/methanol mixed-solvent system. The structure features two-dimensional brick wall sheets that are cross-linked by weak noncovalent pi-pi interactions (alternating face-to-face stacking of coordinated and uncoordinated L1 molecules) to generate a novel three-dimensional network. [Co(NO3)2(L1)(1.5).H2O]n (2; orthorhombic, Ccca; a = 19.031(4) A, b = 33.627(7) A, c = 14.299(3) A, Z = 4) is generated from the reaction of L1 with Co(NO3)(2).6H2O in a benzene/ethanol mixed-solvent system. It forms with a unique three-dimensional framework that can be considered a new polymeric motif based on the 1:1.5 metal-to-ligand composition M(L)1.5. The Cd(II) and Co(II) centers in 1 and 2, which lie in seven-coordinate environments, generate two new types of building blocks. The topologies of these two new building blocks are distinctly different from the common "T-shaped" building block generated from the same (MN3O4) coordination environment reported previously. Cd(L2)2(NO3)2 (3) and Co(L2)2(NO3)2 (4) are obtained by combination of L2 with Cd(NO3)(2).4H2O and Co(NO3)(2).6H2O, respectively. Compounds 3 and 4 are isostructural, crystallizing in the monoclinic space group P2(1)/n, with a = 8.5802(17) A, b = 17.506(4) A, c = 10.443(2) A, beta = 96.59(3) degrees, and Z = 2 for 3 and a = 8.5283(17) A, b = 17.408(4) A, c = 10.229(2) A, beta = 97.05(3) degrees, and Z = 2 for 4. 3 and 4 adopt a novel one-dimensional chain structural motif, consisting of M2(L2)2 (M = Cd, Co) ringlike units. O...H-C hydrogen-bonding interactions in both 3 and 4 play a significant role in aligning the polymer strands in the solid state. PMID- 11196974 TI - Ternary early-transition-metal palladium pnictides Zr3Pd4P3, Hf3Pd4P3, HfPdSb, and Nb5Pd4P4. AB - Several ternary palladium pnictides of the early transition metals have been prepared by arc-melting of the elemental metals and the binary pnictides ZrP, HfP, HfSb2, or NbP, and their structures have been determined by X-ray diffraction methods. The phosphides M3Pd4P3 (M = Zr, Hf) adopt a new structure type (Pearson symbol oP40), crystallizing in the orthorhombic space group Pnma with Z = 4 and unit cell parameters of a = 16.387(2), b = 3.8258(5), and c = 9.979(1) A for Zr3Pd4P3 and a = 16.340(2), b = 3.7867(3), and c = 9.954(1) A for Hf3Pd4P3. The antimonide HfPdSb was identified by powder X-ray diffraction (orthorhombic, Pnma, Z = 4, a = 6.754(1) A, b = 4.204(1) A, and c = 7.701(2) A) and confirmed to be isostructural to ZrPdSb, which adopts the TiNiSi-type structure. The phosphide Nb5Pd4P4 adopts the Nb5Cu4Si4-type structure, crystallizing in the tetragonal space group I4/m with Z = 2, a = 10.306(1) A, and c = 3.6372(5) A. Coordination geometries of pentacapped pentagonal prisms for the early transition metal, tetracapped distorted tetragonal prisms for Pd, and tricapped trigonal prisms for the pnicogen are found in the three structures; tetracapped tetragonal prisms for Nb are also found in Nb5-Pd4P4. In common with many metal-rich compounds whose metal-to-nonmetal ratio is equal or close to 2:1, the variety of structures formed by these ternary palladium pnictides arises from the differing connectivity of pnicogen-filled trigonal prisms. Pnicogen-pnicogen bonds are absent in these structures, but metal-metal bonds (in addition to metal pnicogen bonds) are important interactions, as verified by extended Huckel band structure calculations on Zr3Pd4P3. PMID- 11196975 TI - Recognition of DNA base pair mismatches by a cyclometalated Rh(III) intercalator. AB - Two cyclometalated complexes of Rh(III), rac-[Rh(ppy)2chrysi]+ and rac-[Rh(ppy)2 phi]+, have been synthesized and characterized with respect to their binding to DNA. The structure of rac-[Rh(ppy)2 phi]Cl.H2O.CH2Cl2 has been determined by X ray diffraction (monoclinic, P2(1)/c, Z = 4, a = 18.447(3) A, b = 9.770(1) A, c = 17.661(3) A, beta = 94.821(11) degrees, V = 3172.0(8) A3) and reveals that the complex is a distorted octahedron with nearly planar ligands, similar in structure to the DNA mismatch recognition agent [Rh(bpy)2chrysi]3+. The 2 phenylpyridyl nitrogen atoms are shown to be in the axial positions, as a result of trans-directing effects. This tendency simplifies the synthesis and purification of such complexes by limiting the number of possible isomers generated. The abilities of [Rh(ppy)2chrysi]+ and [Rh(ppy)2 phi]+ to bind and, with photoactivation, to cleave DNA have been demonstrated in assays on duplex DNA in the absence and presence of a single CC mismatch. [Rh(ppy)2chrysi]+ was shown upon photoactivation to cleave DNA selectively at the base pair mismatch whereas [Rh(ppy)2 phi]+ cleaves B-DNA nonspecifically. The reactivity of [Rh(ppy)2chrysi]+ was also compared to that of the known mismatch recognition agent [Rh(bpy)2chrysi]3+. Competitive photocleavage studies revealed that a 14 fold excess of [Rh(ppy)2chrysi]+ was required to achieve the same level of binding as that of [Rh(bpy)2chrysi]3+. However, the ratio of damage induced by [Rh(bpy)2chrysi]3+ to that induced by [Rh(ppy)2chrysi]+ is considerably greater than this value, indicating that decreased photoefficiency for the cyclometalated complex must contribute to its significantly attenuated photoreactivity. These cyclometalated intercalators provide the starting points for the design of a new family of metal complexes targeted to DNA. PMID- 11196976 TI - Copper(II) and nickel(II) complexes of binucleating macrocyclic bis(disulfide)tetramine ligands. AB - Novel macrocyclic bis(disulfide)tetramine ligands and several Cu(II) and Ni(II) complexes of them with additional ligands have been synthesized by the oxidative coupling of linear tetradentate N2S2 tetramines with iodine. Facile demetalation of the Ni(II) oxidation products affords the free 20-membered macrocycles meso-9 and rac-9 and the 22-membered macrocycle 16, all of which are potentially octadentate N4S4 ligands. X-ray structure analyses reveal distinctly different conformations for the two isomers of 9; meso-9 shows a stepped conformation in profile with the disulfide groups corresponding to the rise of the step, whereas rac-9 exhibits a V conformation with the disulfide groups near the vertex of the V. No metal complexes of rac-9 have been isolated. Crystallographic studies of three Cu(II) complexes reveal that depending upon the size of the macrocyclic ligand and the nature of the additional ligands (I-, NCO-, and CH3CN), the Cu(II) coordination geometry shows considerable variation (plasticity), with substantial changes in the Cu(II)-disulfide bonding. Thus, a diiodide salt contains six coordinate Cu(II) to which all four bridging disulfide sulfur atoms form strong equatorial bonds. In contrast, isocyanato complexes of the 20- and 22-membered macrocycles exhibit trigonal-bipyramidal Cu(II) and distorted cis-octahedral Cu(II) geometries, respectively, having only one and no short equatorially bound sulfur atoms. The coordination geometry of the latter complex can also be described as four-coordinate seesaw with two semicoordinated S(disulfide) ligands. Disulfide-->Cu(II) ligand-to-metal charge transfer absorptions of both isocyanato-containing Cu(II) species appear too weak to observe, probably because of poor overlap of the sulfur orbitals with the Cu(II) d-vacancy. The dual disulfide-bridged Ni(II) units of the crystallographically characterized octahedral Ni(II) complex of meso-9 with axial iodide and acetonitrile ligands promote substantial antiferromagnetic coupling (J = -13.0(2) cm-1). PMID- 11196977 TI - Allosteric manipulation of photoexcited state relaxation in (bpy)2RuII(binicotinic acid). AB - The emission spectrum and luminescent lifetime of (bpy)2RuII(binicotinic acid) is affected by the presence of heavy metal ions in solution. As little as 1 microM Pb2+ causes a red shift in emission, an increase in the emission quantum yield, and an increase in the room-temperature lifetime. A smaller red shift is observed in the 4,4'-dicarboxy analogue in the presence of large quantities of lead; however, the emission lifetime and intensity are diminished. An X-ray determination of the ground-state geometry shows that the bipyridine rings of the binicotinic acid are twisted along the 2,2' bond by 19.3 degrees. The interaction between lead and the binicotinic acid complex was modeled by molecular mechanics and extended Huckel calculations. The calculations show that interaction with lead flattens the bridged ring system of the binicotinic acid ligand, which affects the pi* energy levels of the ligand, the d-orbital energies of the Ru(II), and the vibrational modes available to the substituted bipyridine ligand. The inverse energy gap law behavior observed in the binicotinic acid complex is explained in terms of an allosteric interaction between lead and the binicotinic acid complex. PMID- 11196979 TI - Reversible and site-specific reduction of the ligand sides in a molecular rectangle with up to eight electrons. PMID- 11196978 TI - Kinetics of metal-mediated one-electron oxidation of guanine in polymeric DNA and in oligonucleotides containing trinucleotide repeat sequences. AB - The oxidation of guanines in DNA by Ru(III) is investigated by catalytic electrochemistry and stopped-flow spectrophotometry. The reactions of calf thymus DNA (20% guanine) and herring testes DNA (25% guanine) with Ru(bpy)3(3+) (bpy = 2,2'-bipyridine) show biexponential decays in stopped-flow spectrophotometric experiments with the fast and slow components in 2:1 ratios and average rate constants in 880 mM NaCl of = 18,700 M-1 s-1 for calf thymus DNA and = 24,600 M-1 s-1 for herring testes DNA. The higher rate constant for the more guanine-rich DNA is possibly due to a higher density of electron-rich guanine multiplets. The observation of a biexponential decay is incorporated into digital simulations of the catalytic voltammograms observed for Ru(bpy)3(2+) in the presence of DNA. For both DNAs, the rates observed by voltammetry are somewhat slower than those observed by stopped-flow spectrophotometry and the dependence of the rate constants on scan rate using the biexponential model is less pronounced than when only one decay is treated, supporting the notion that the scan rate dependence arises from the multiphasic decay. At low salt concentrations, where binding of the metal complex to DNA increases the effective catalytic rate constant, rates can be measured by stopped-flow spectrophotometry only with a less oxidizing complex, Fe(bpy)3(3+/2+), which yields trends in the rate constants similar to those observed for the case of Ru(bpy)3(3+/2+) at high ionic strength. Oligonucleotides based on the trinucleotide repeat sequences (AGT)n and (GAA)n produce significant catalytic currents, which are readily interpreted in terms of the guanine concentration and the secondary structure discerned from gel electrophoresis experiments. These experiments may provide a basis for sensing secondary structures and repeat numbers in biologically relevant DNAs. PMID- 11196980 TI - Dimeric bridged and chelated alkali metal (Li and Na) bis(iminophosphorano)methanide complexes with contrasting structures. PMID- 11196981 TI - Synthesis and structure of (H3NC2H4NH3)2Co7(PO4)6: a novel open framework cobalt phosphate. PMID- 11196982 TI - ESEEM and mims ENDOR spectroscopies of cis,trans-(L-N2S2)MoVO(SCH2Ph): detection of the two benzylthiolate alpha protons. PMID- 11196983 TI - Pictures of Charles Darwin. PMID- 11196984 TI - Founders of American Geology. Meeting: History of Geologic Pioneers, Troy, New York, USA; 3-5th August, 2000. PMID- 11196985 TI - The use of colours on the the seventeenth century royal warship Vasa. AB - The seventeenth-century Swedish Royal warship Vasa was painted and decorated with almost 500 figure sculptures and many carved ornaments. It is probably the most extensive sculptural work in wood to have been preserved from this period in European history. The ship's decorations are of particular importance given the scarcity of knowledge of how sculptures in general, and large ships in particular, were painted in Northern Europe during this period. About 20 different pigments have been characterized and it has been possible to reconstruct the appearance of many of the sculptures and to extend this knowledge to the ship's original appearance. PMID- 11196986 TI - The mathematical and military sciences in Renaissance England. AB - The Renaissance saw the evolution of troop management, fortification and artillery into 'mathematical' sciences and those who practiced these tasks into 'mathematical practitioners'. These terms have been allowed to imply that these areas were deeply theoretical, whereas they varied from theoretical to simply numerical. Gunnery, in particular, tended towards the latter. Practitioners of the simpler mathematics, however, gained by being able to connect their action to the more impressive study of 'the mathematicks'. Future work must recognize more critically the distinction inherent in the term 'mathematical' when applied to the arts of the Renaissance. PMID- 11196987 TI - Diffusion of astronomy in the ancient world. AB - Astronomical techniques, calendars and devices were developed independently in many places around the world. However, there was much cross-cultural exchange of technology over the centuries. The cultures of Egypt, Greece, India and China influenced each others' astronomy and each cannot be treated in isolation. PMID- 11196988 TI - Humphry Davy: science and social mobility. AB - Humphry Davy (1778-1829) was one of the first professional scientists, earning his living and rising spectacularly from an impoverished upbringing in Cornwall to be President of the Royal Society and a baronet. He owed his rise to patronage as well as to his range of abilities: as a lecturer, as a chemical theorist and as a very early applied scientist. But his exalted position brought him little happiness, for he could not satisfy all the hopes put upon him as the successor to Sir Joseph Banks. Admired rather than loved, he became unpopular and was seen as haughty. In his last two years, spent wandering lonely and sickly in Italy and the Alps, he sought to make sense of his life, writing dialogues as his bequest to the new generation. PMID- 11196989 TI - Elegant hypothesis and inelegant fact in developmental biology. AB - The relationship between theoretical and experimental approaches to the problem of pattern generation during embryonic development has often been uneasy. This stems at least in part from the different emphases that have typically been used in the two approaches. The spectacular success of modern genetic techniques in uncovering developmental mechanisms has led to a widespread belief that theory is no longer very relevant. However, recent examples of data-driven modelling point to new roles for theoretical approaches in exploring important issues such as the robustness and evolution of pattern-forming mechanisms. PMID- 11196990 TI - Applications of laser desorption and electrospray ionization mass spectrometry at the transition between clusters and colloids. PMID- 11196991 TI - A homologous series of redox-active, dinuclear cations with the bridging ligand 2 (2-pyridyl)-1,8-naphthyridine. PMID- 11196992 TI - Mechanistic role of benzylic bromides in the catalytic autoxidation of methylarenes. AB - Different pathways for benzylic bromide transformations were examined under conditions of cobalt-bromide catalysis in acetic acid. It has been shown that benzylic bromides participate in the catalytic cycle through their catalyzed and noncatalyzed oxidation, through their reaction with Co(III), and through cobalt(II)-catalyzed solvolysis. The rates of the direct reduction of Co(III) by several benzylic bromides were measured under an argon atmosphere; the reaction occurs by a mechanism involving two forms of Co(III). The same reaction under an oxygen atmosphere initiates the cobalt-bromide-catalyzed oxidation of benzyl bromide, thus leading to the regeneration of inorganic bromide and the fast reduction of Co(III). Solvolysis of benzylic bromides plays only a minor role in the regeneration of inorganic bromide in glacial acetic acid. PMID- 11196993 TI - Aminopyridine iron catecholate complexes as models for intradiol catechol dioxygenases. Synthesis, structure, reactivity, and spectroscopic studies. AB - Four new Fe(III) catecholate complexes, [(bispicMe2en)FeIII(DBC)]+, [(bispicCl2Me2en)FeIII(DBC)]+, [(trispicMeen)FeIII(DBC)]+, and [(BQPA)FeIII(DBC)]+, which all contain aminopyridine ligands, were synthesized. The structure of [(bispicMe2en)FeIII(DBC)]+ was determined by X-ray diffraction. It crystallizes in the triclinic space group P1 with a = 10.666(3) A, b = 13.467(5) A, c = 17.685(2) A, alpha = 93.46(2) degrees, beta = 93.68(2) degrees, gamma = 109.0(3) degrees, V = 2387.4 A3, and Z = 2. All of these complexes were found to be active toward oxidation of catechol by O2 in DMF at 20 degrees C to afford intradiol cleavage products. The catechol was quantitatively oxidized, mainly (90%) into 3,5-di-tert-butyl-5-(carboxymethyl)-2-furanone. Reaction rates were measured, and for the first three (topologically similar) complexes, a correlation of the second-order kinetic constants k with the optical parameters of the two LMCT O(DBC)-->Fe(III) bands was found. In particular, k increases with the epsilon max of the charge-transfer bands. The k value of the complex [(BQPA)FeIII(DBC)]+, containing a tripodal ligand, is smaller than expected on the basis of these correlations. This discrepancy could be related to steric hindrance induced by the BQPA ligand. However, the much lower activity of the bispicen-Fe(III)-type complexes compared to that of the [(TPA)FeIII(DBC)]+ complex synthesized by Jang et al. (J. Am. Chem. Soc. 1991, 113, 9200-9204), despite similar epsilon max values, shows that a knowledge of optical and NMR parameters values is not sufficient to explain the dioxygenase activity rate. In their study of protocatechuate 3,4-dioxygenase, Orville et al. (Biochemistry 1997, 36, 10052-10066) suggested that asymmetric chelation of the catecholate to Fe(III) is of great importance in the efficiency of the intradiol dioxygenase reaction. Indeed, a comparison of the X-ray structures of [(TPA)FeIII(DBC)]+ and [(bispicMe2en)FeIII(DBC)]+ shows that the Fe(III)-O bonds differ by 0.019 A in the former and are identical in the latter. Asymmetry could also play a role in the model complexes. An alternative explanation is the possible existence of a low-spin state for [(TPA)FeIII(DBC)]+, as recently identified in [(TPA)FeIII(cat)]+ by Simaan et al. PMID- 11196994 TI - Synthesis and structural characterization of configurational isomers of tungsten palladium complexes with bridging diphenyl(dithioalkoxycarbonyl)phosphine as a ligand and phosphine transfer from tungsten to palladium. AB - Treatment of the complex [W(CO)5[PPh2(CS2Me)]] (2) with [Pd(PPh3)4] (1) affords binuclear complexes such as anti-[(Ph3P)2Pd[mu-eta 1,eta 2-(CS2Me)PPh2]W(CO)5] (3), syn-[(Ph3P)2Pd[mu-eta 1,eta 2-(CS2Me)PPh2]W(CO)5] (4), and trans [W(CO)4(PPh3)2] (5). In 3 and 4, respectively, the W and Pd atoms are in anti and syn configurations with respect to the P-CS2 bond of the diphenyl(dithiomethoxycarbonyl)phosphine ligand, PPh2(CS2Me). Complex 3 undergoes extensive rearrangement in CHCl3 at room temperature by transfer of a PPh3 ligand from Pd to W, eliminating [W(CO)5(PPh3)] (7), while the PPh2CS2Me ligand transfers from W to Pd to give [[(Ph3P)Pd[mu-eta 1,eta 2-(CS2Me)PPh2]]2] (6). In complex 6, the [Pd(PPh3)] fragments are held together by two bridging PPh2(CS2Me) ligands. Each PPh2(CS2Me) ligand is pi-bonded to one Pd atom through the C=S linkage and sigma-bonded to the other Pd through the phosphorus atom, resulting in a six-membered ring. Treatment of Pd(PPh3)4 with [W(CO)5[PPh2[CS2(CH2)nCN]]] (n = 1, 8a; n = 2, 8b) in CH2Cl2 affords syn-[(Ph3P)2Pd[mu-eta 1,eta 2 [CS2(CH2)nCN]PPh2]W(CO)5] (n = 1, 9a; n = 2, 9b). Similar configurational products syn-[(Ph3P)2Pd[mu-eta 1,eta 2-(CS2R)PPh2]W(CO)5] (R = C2H5, C3H5, C2H4OH, C3H6CN, 11a-d) are synthesized by the reaction of Pd(PPh3)4 with [W(CO)5[PPh2(CS2R)]] (R = C2H5, C3H5, C2H4OH, C3H6CN, 10a-d). Although complexes 11a-d have the same configuration as 9a,b, the SR group is oriented away from Pd in the former and near Pd in the latter. In these complexes, the diphenyl(dithioalkoxycarbonyl)phosphine ligand is bound to the two metals through the C=S pi-bonding and to phosphorus through the sigma-bonding. All of the complexes are identified by spectroscopic methods, and the structures of complexes 3, 6, 9a, and 11d are determined by single-crystal X-ray diffraction. Complexes 3, 9, and 11d crystallize in the triclinic space group P1 with Z = 2, whereas 6 belongs to the monoclinic space group P2/c with Z = 4. The cell dimensions are as follows: for 3, a = 10.920(3) A, b = 14.707(5) A, c = 16.654(5) A, alpha = 99.98(3) degrees, beta = 93.75(3) degrees, gamma = 99.44(3) degrees; for 6, a = 15.106(3) A, b = 9.848(3) A, c = 20.528(4) A, beta = 104.85(2) degrees; for 9a, a = 11.125(3) A, b = 14.089(4) A, c = 17.947(7) A, alpha = 80.13(3) degrees, beta = 80.39(3) degrees, gamma = 89.76(2) degrees; for 11d, a = 11.692(3) A, b = 13.602(9) A, c = 18.471(10) A, alpha = 81.29(5) degrees, beta = 80.88(3) degrees, gamma = 88.82(1) degrees. PMID- 11196995 TI - Synthesis and characterization of Rhodium(III) dichloro complexes with unsymmetrically bound salen-type ligands. AB - We have synthesized a series of novel octahedral Rh(III) salen-type complexes where the salen ligand is unsymmetrically bound to the Rh(III) dichloride center. This mode of bonding left one intact phenol group coordinating to the rhodium center and has never before been observed in salen-metal chemistry. These remarkably stable complexes possess unique coordination geometry and represent the first time that Rh(III) salen complexes have been successfully isolated from the direct combination of RhCl(3).3H2O and the salen ligand in the absence of a nucleophilic base. The (salen)Rh(III) dichloride complex can be converted to the analogous monochloride complex by reaction with metal carbonate salts. PMID- 11196996 TI - Synthesis, characterization, and structure of macrocyclic mono- and C2-symmetric, binuclear nickel calixsalen complexes. AB - Mono- (3a,b) and binuclear (4a,b) tetradentate NiII complexes of a series of 26 membered macrocyclic salen dimers, [salen(CH2)]2, are prepared in good yield by solvent-controlled reaction with Ni(OAc)2. The mononuclear complex 3b crystallizes in the trigonal space group 3P1(#144), a = 18.2566(2) A, c = 15.9244(2) A, V = 4596.57(8) A3, and Z = 3. Refinement converged with R = 0.054 and Rw = 0.049 for 6852 reflections with I > 2.003 sigma(I). The NiII in complex 3b coordinates in an approximate square planar geometry to one of the two available tetradentate salen sites. Complex 4b crystallizes in the orthorhombic space group P2(1)2(1)2(1)(#19), a = 19.531(2) A, b = 22.891(3), c = 13.373(1) A, V = 5960(1) A3, and Z = 4. The refinement converged with R = 0.067 and Rw = 0.065 for 3752 reflections with I > 2.003 sigma(I). Complex 4b coordinates two distorted square planar, cofacially oriented NiII-salen units held 7.1 A apart by a rigid, syn-folded macrocyclic structure. The solution spectroscopic data and solid-state crystallographic data of 3b and 4b demonstrate the presence of a molecular-sized cavity which shows host-guest properties. Reaction of the flexible 32-membered disalen macrocycle [salen(OCH2CH2O)]2 with Ni(OAc)2 resulted in formation of a binuclear complex, 5. Complex 5 crystallizes in the triclinic space group P1(#1), a = 10.366(4) A, b = 12.170(3) A, c = 10.021(2) A, alpha = 106.29(2) degrees, beta = 91.69(2) degrees, gamma = 68.63(2) degrees, V = 1126.3(5) A3, and Z = 1. The refinement converged with R = 0.052 and Rw = 0.053 for 2385 reflections with I > 2.003 sigma(I). The binuclear complex 5 contains two cofacially oriented, square planar NiII-salen groups lying 3.5 A apart in an anti-folded macrocyclic structure. PMID- 11196997 TI - Ligand binding inside the cavities of lacunar and saddle-shaped cyclidene complexes: molecular mechanics and molecular dynamics studies. AB - Cobalt(II) complexes with tetradentate macrocyclic cyclidene ligands are known to coordinate one additional axial base molecule, leaving the sixth vacant coordination site at the metal ion available for small ligand (e.g., O2) binding. Molecular mechanics and molecular dynamics simulations provide a microscopic view of 1-methylimidazole (MeIm) binding within the cavities of several lacunar (bridged) and saddle-shaped (unbridged) cyclidenes and uncover the roles of the bridges and the walls of the clefts in steric protection of the cobalt(II) coordination site. Short bridges (C3 and C6) prevent inside-the-cavity MeIm binding because of severe ligand distortions leading to high-energy penalties (58 and 25 kcal/mol, respectively), while long bridges (C8 and C12) flip away from the MeIm binding site, allowing for penalty-free MeIm inclusion. In the unbridged saddle-shaped complex, there is no energy difference between inside- and outside the-cavity MeIm binding. The preferential existence of the coordinatively unsaturated, five-coordinate species Co(unbrCyc)(MeIm)2+ should therefore be explained by electronic, rather than steric, factors. Molecular dynamics and free energy simulations reveal the presence of a weak (ca. 4 kcal/mol in the gas phase and ca. 2 kcal/mol in methanol solution) noncovalent MeIm binding site at the entrance of the cleft of cobalt(II) unbridged cyclidene, at a distance of about 4 A from the metal ion. The macrocycle geometry remains undistorted at such large Co-N(MeIm) separations, while the cavity opens up by 0.9 A upon covalent MeIm binding (Co-N(MeIm) distance of 2 A). An increase in macrocycle strain energy upon MeIm inclusion is compensated by favorable nonbonded interactions between the incoming base and the walls of the unbridged cyclidene. PMID- 11196998 TI - Fluoride ion donor properties of TcO2F3 and ReO2F3: X-ray crystal structures of MO2F3.SbF5 (M = Tc, Re) and TcO2F3.XeO2F2 and Raman and NMR spectroscopic characterization of MO2F3.PnF5 (Pn = As, Sb), [ReO2F2(CH3CN)2][SbF6], and [Re2O4F5][Sb2F11]. AB - The fluoride ion donor properties of TcO2F3 and ReO2F3 toward AsF5, SbF5, and XeO2F2 have been investigated, leading to the formation of TcO2F3.PnF5 and ReO2F3.PnF5 (Pn = As, Sb) and TcO2F3.XeO2F2, which were characterized in the solid state by Raman spectroscopy and X-ray crystallography. TcO2F3.SbF5 crystallizes in the monoclinic system P2(1)/n, with a = 7.366(2) A, b = 10.441(2) A, c = 9.398(2) A, beta = 93.32(3) degrees, V = 721.6(3) A3, and Z = 4 at 24 degrees C, R1 = 0.0649, and wR2 = 0.1112. ReO2F3.SbF5 crystallizes in the monoclinic system P2(1)/c, with a = 5.479(1) A, b = 10.040(2) A, c = 12.426(2) A, beta = 99.01(3) degrees, V = 675.1(2) A3, and Z = 4 at -50 degrees C, R1 = 0.0533, and wR2 = 0.1158. TcO2F3.XeO2F2 crystallizes in the orthorhombic system Cmc2(1), with a = 7.895(2) A, b = 16.204(3) A, c = 5.198(1) A, beta = 90 degrees, V = 665.0(2) A3, and Z = 4 at 24 degrees C, R1 = 0.0402, and wR2 = 0.0822. The structures of TcO2F3.SbF5 and ReO2F3.SbF5 consist of infinite chains of alternating MO2F4 and SbF6 units in which the bridging fluorine atoms on the antimony are trans to each other. The structure of TcO2F3.XeO2F2 comprises two distinct fluorine-bridged chains, one of TcO2F3 and the other of XeO2F2 bridged by long Tc-F...Xe contacts. The oxygen atoms of the group 7 metals in the three structures are cis to each other and to two terminal fluorine atoms and trans to the bridging fluorine atoms. The 19F NMR and Raman spectra of TcO2F3.PnF5 and ReO2F3.PnF5 in SbF5 and PnF5-acidified HF solvents are consistent with dissociation of the adducts into cis-MO2F2(HF)2+ cations and PnF6- anions. The energy-minimized geometries of the free MO2F2+ cations and their HF adducts, cis MO2F2(HF)2+, have been calculated by local density functional theory (LDFT), and the calculated vibrational frequencies have been used as an aid in the assignment of the Raman spectra of the solid MO2F3.PnF5 adducts and their PnF5-acidified HF solutions. In contrast, ReO2F3.SbF5 ionizes in SO2ClF solvent to give the novel Re2O4F5+ cation and Sb2F11- anion. The 19F NMR spectrum of the cation is consistent with two ReO2F2 units joined by a fluorine bridge in which the oxygen atoms are assumed to lie in the equatorial plane. The [ReO2F2(CH3CN)2][SbF6] salt was formed upon dissolution of ReO2F3.SbF5 in CH3CN and was characterized by 1H, 13C, and 19F NMR and Raman spectroscopies. The ReO2F2(CH3CN)2+ cation is a pseudooctahedral cis-dioxo arrangement in which the CH3CN ligands are trans to the oxygens and the fluorines are trans to each other. PMID- 11196999 TI - Structures and magnetism of two novel heptanuclear lanthanide-centered trigonal prismatic clusters: [LnCu6(mu 3-OH)3(HL)2(L)4](ClO4)2.25H2O (Ln = La, Tb; H2L = iminodiacetic acid). AB - The new heteronuclear iminodiacetic acid (H2L) complexes [LnCu6(mu 3 OH)3(HL)2(L)4](ClO4)(2).25H2O with Ln = La (1) and Tb (2) have been prepared in aqueous solution and characterized by single-crystal X-ray diffraction to be isomorphous (crystallographic data for 1 and 2: hexagonal, P63/m; a = b = 12.6425(14) A, c = 24.541(5) A, Z = 2 (1); a = b = 12.5802(9) A, c = 24.285(4) A, Z = 2 (2)). Ln3+ was found to be located in the center of the trigonal prismatic cage formed by six Cu2+ ions, with a tricapped trigonal prismatic coordination environment of nine O atoms. The magnetic properties of complexes 1 and 2 have been studied. The results indicate the presence of ferromagnetic couplings between Tb3+ and Cu2+ in compound 2. PMID- 11197000 TI - Studies of the synthesis and thermochemistry of coordinatively unsaturated chelate complexes (eta 5-C5Me5)IrL2 (L2 = TsNCH2CH2NTs, TsNCH2CO2, CO2CO2). AB - A comparative synthetic, structural, and thermochemical study on a series of chelate complexes containing the fragment (eta 5-C5Me5)Ir [(eta 5 C5Me5)Ir(TsNCH2CH2NTs) (1), (eta 5-C5Me5)Ir(TsNCH2CO2) (2), (eta 5 C5Me5)Ir(CO2CO2) (3)] was performed to clarify the roles of carboxylato and sulfonamido ligands. Whereas 1 and 2 are monomeric in solution and in the solid state, 3 appears to exist as an oligomer or polymer, (3)n, which can be broken up by addition of a ligand L such as a phosphine, CO, or 2-methoxypyridine to form (eta 5-C5Me5)Ir(L)(CO2CO2) (6). The synthesis of (3)n from [(eta 5-C5Me5)IrCl(mu Cl)]2 required the use of silver oxalate in CH3CN, but if other solvents were used, the bridging oxalato complex (eta 5-C5Me5)IrCl(mu-eta 2-eta 2-C2O4)ClIr(eta 5-C5Me5) (7) was obtained and identified by X-ray diffraction. Enthalpies for reaction of THF-soluble monomers 1 and 2 with PMe3 were determined to be 28.7(0.5) and -28.5(0.4) kcal mol-1, respectively. The oligomerization behavior of 3 may be a result of reduced sigma- or pi-donation of carboxylato ligands compared to N-tosylamido ligands, because the values for nu CO in oxalato and bissulfonamido complexes 6-CO and (eta 5-C5Me5)Ir(CO)(TsNCH2CH2NTs) (4-CO) were 2064 and 2042 cm-1, respectively. PMID- 11197001 TI - Automated solid-phase synthesis and photophysical properties of oligodeoxynucleotides labeled at 5'-aminothymidine with Ru(bpy)2(4-m-4'-cam bpy)2+. AB - A facile and automated procedure for the incorporation of a derivatized Ru(bpy)3(2+) in an oligodeoxynucleotide is reported. The Ru(bpy)3(2+)-thymidine phosphoramidite is synthesized, and then incorporated in DNA using a standard protocol on an automated DNA solid-phase synthesizer. The structure of the DNA duplex is not altered after labeling with Ru(bpy)3(2+). Photophysical studies of the novel ruthenium trisdiimine thymidine complex as well as the corresponding labeled oligodeoxynucleotides demonstrate that the favorable properties associated with the ruthenium complex are retained after covalent attachment to the nucleoside and oligodeoxynucleotide. PMID- 11197002 TI - Polylithiated tetraaminosilanes: synthesis and characterization of (Et2O.Li)4[Si(Nnaph)4] and X-ray structure of (THF.Li3[Si(NiPr)3(NHiPr)])2. AB - The treatment of SiCl4 with 4 equiv of Li2(Nnaph) (naph = 1-naphthyl) in diethyl ether gives (Et2O.Li)4[Si(Nnaph)4] (4), which, upon reaction with excess tBuNH3Cl or MeO3SCF3, generates Si[N(H)naph]4 (5) or Si[N(Me)naph]4 (6), respectively. The centrosymmetric dimer (THF.Li3[Si(NiPr)3(NHiPr)])2 (7), formed via trilithiation of Si[N(H)iPr]4 with n-butyllithium, consists of a bis-THF-solvated Li6(NiPr)6 cyclic ladder bicapped by two SiN(H)iPr units. Crystal data for 7: C32H74Li6N8O2Si2, monoclinic, P2(1)/n, a = 10.661(7) A, b = 16.964(5) A, c = 12.405(4) A, beta = 93.22(4) degrees, V = 2239.9(15) A3, and Z = 2. PMID- 11197003 TI - Synthesis of stable crystals of a self-assembled centered icosahedral samarium cluster formed by bis(L-prolinato)nickel(II) ligands. AB - A centered icosahedral 12-coordinate samarium cluster formed by six bis(L prolinato)nickel(II) ([Ni(pro)2]) ligands, [Sm(Ni(pro)2)6]3+, was prepared. The reaction of Sm with [Ni(pro)2] in a small excess (a 2-fold excess) and also in a large excess (even a 10-fold excess) of the latter produced the cluster. Therefore, this system is a self-assembly. In the cluster, each nickel atom is surrounded by six atoms: two amino nitrogens, two carboxylate oxygens which form chelate rings with the nitrogen atoms, and two carboxylate oxygen atoms which link the neighboring nickel atoms. The samarium atom is coordinated by six [Ni(pro)2] ligands, and the metal is in an icosahedral environment formed by 12 oxygen atoms. The icosahedral geometry is almost ideal. Crystals of [Sm(Ni(pro)2)6](ClO4)3.6MeOH, which were prepared from a methanol solution, immediately decompose after filtration because of loosely trapped MeOH molecules in the crystal lattice. Therefore, crystals without MeOH molecules, which must be stable, were prepared by recrystallization from acetonitrile with tetramethylammonium perchlorate (TMAP). According to the X-ray crystal analysis, the cluster is TMA[Sm(Ni(pro)2)6](ClO4)4, cubic of space group F23, with a = 21.273(9) A, V = 9626(1) A3, and Z = 4; R = 0.053 (Rw = 0.049) for 1296 reflections. In addition, several crystals of cluster salts that have different counteranions, i.e., tetrafluoroborate (BF4-), hexafluorophosphate (PF6-), iodide (I-), and nitrate (NO3-), were prepared. The order of increasing ease of crystallization of the cluster salts was I- > PF6- approximately ClO4- > BF4- >> NO3-. The cluster structure is retained in alcohol and acetonitrile solutions; the UV-vis spectra of the solutions are perfectly consistent with the powder diffuse reflection spectrum. Cyclic voltammograms of [Sm(Ni(pro)2)6]3+ in acetonitrile proved that the structure of [Sm(Ni(pro)2)6]3+ is retained in the redox process and that the nickel atoms electrochemically interact with one another. Thermal analysis of the cluster salts with different counteranions was investigated. The results imply that the cluster is very stable until bis(L prolinato)nickel(II) ligands, which form the cage structure, disintegrate and that the thermal decomposition processes of the cluster salts depend on their counteranions. PMID- 11197004 TI - Electron paramagnetic resonance and spectroscopic characteristics of electrogenerated mixed-valent systems [(eta 5-C5Me5)M(mu-L)M(eta 5-C5Me5)]+ (M = Rh, Ir; L = 2,5-diiminopyrazines) in relation to the radicals [(eta 5 C5Me5)ClM(mu-L)MCl(eta 5-C5Me5)]+ and [(eta 5-C5Me5)M(mu-L)MCl(eta 5-C5Me5)]2+. AB - Electrochemical reduction of the dinuclear [(eta 5-C5Me5)ClM(mu-L)MCl(eta 5 C5Me5)]2+ ions (M = Rh, Ir; L = 2,5-bis(1-phenyliminoethyl)pyrazine (bpip) and 2,5-bis[1-(2,6-dimethylphenyl)iminoethyl]pyrazine (bxip)) proceeds via the paramagnetic intermediates [(eta 5-C5Me5)ClM(mu-L)MCl(eta 5-C5Me5)]+ (L = bpip) or [(eta 5-C5Me5)M(mu-L)MCl(eta 5-C5Me5)]2+ (L = bxip) and [(eta 5-C5Me5)M(mu L)M(eta 5-C5Me5)]+. Whereas the first is clearly a radical species with a small g anisotropy, the chloride-free cations are distinguished by structured intervalence charge transfer (IVCT) bands in the near-infrared region and by rhombic electron paramagnetic resonance features between g = 1.9 and g = 2.3, which suggests considerable metal participation at the singly occupied MO. Alternatives for the d configuration assignment and for the role of the bisbidentate-conjugated bridging ligands will be discussed. The main difference between bpip and bxip systems is the destabilization of the chloride-containing forms through the bxip ligand for reasons of steric interference. PMID- 11197005 TI - Ferromagnetism in an extended three-dimensional, diamond-like copper(II) network: a new copper(II)/1-hydroxybenzotriazolato complex exhibiting soft-magnet properties and two transitions at 6.4 and 4.4 K. AB - The use of the substituted benzotriazole ligand btaOH (1-hydroxybenzotriazole) in copper(II) chemistry has yielded a structurally and magnetically very interesting complex. The [Cu2(O2CMe)4(H2O)2]/btaOH.H2O/aqueous NH3 (1:4:4, 1:3:3, 1:2:2) reaction system in MeOH gives dark brown-green [Cu(btaO)2(MeOH)]n (4) in approximately 80% yield. 4 crystallizes in the tetragonal space group P4(3)2(1)2 with (at 25 degrees C) a = 9.915(1) A, b = 9.915(1) A, c = 14.715(2) A, and Z = 4. The structure consists of a 3D, diamond-like copper(II) lattice. The CuII atom has a square pyramidal geometry with four btaO- ligands at the basal plane. The btaO- ion functions as a bidentate bridging ligand, with N(3) and the deprotonated oxygen being the ligating atoms. Dc and ac magnetic susceptibility measurements, together with low-field (10 G) and high-field (up to 5000 G) magnetization data, are consistent with ferromagnetic interactions on the scale of the crystal lattice with two critical temperatures: 6.4 and 4.4 K. The former critical temperature could correspond to a transition from a paramagnetic to a ferromagnetic state; the latter one, to a transition from a ferromagnetically ordered state to its 3D ordering. The magnetic data, along with the field dependence of the magnetization and the EPR data, are also in line with a soft magnet. Moreover, the EPR studies performed on 4 reveal unique features reported for the first time in the field of molecular magnetism. PMID- 11197006 TI - 19F NMR study of the equilibria and dynamics of the Al3+/F- system. AB - A careful reinvestigation by high-field 19F NMR (470 MHz) spectroscopy has been made of the Al3+/F- system in aqueous solution under carefully controlled conditions of pH, concentration, ionic strength (I), and temperature. The 19F NMR spectra show five distinct signals at 278 K and I = 0.6 M (TMACl) which have been attributed to the complexes AlFi(3-i)+(aq) with i < or = 5. There was no need to invoke AlFi(OH)j(3-i-j)+ mixed complexes in the model under our experimental conditions (pH < or = 6.5), nor was any evidence obtained for the formation of AlF6(3-)(aq) at very high ratios of F-/Al3+. The stepwise equilibrium constants obtained for the complexes by integration of the 19F signals are in good agreement with literature data given the differences in medium and temperature. In I = 0.6 M TMACl at 278 K and in I = 3 M KCl at 298 K the log Ki values are 6.42, 5.41, 3.99, 2.50, and 0.84 (for species i = 1-5) and 6.35, 5.25, and 4.11 (for species i = 1-3), respectively. Disappearance of the 19F NMR signals under certain conditions was shown to be due to precipitation. Certain 19F NMR signals exhibit temperature- and concentration-dependent exchange broadening. Detailed line shape analysis of the spectra and magnetization transfer measurements indicate that the kinetics are dominated by F- exchange rather than complex formation. The detected reactions and their rate constants are AlF2(2+) + *F- reversible AlF*F2+ + F- (k02 = (1.8 +/- 0.3) x 10(6) M-1 s-1), AlF3(0) + *F- reversible AlF2*F0 + F- (k03 = (3.9 +/- 0.9) x 10(6) M-1 s-1), and AlF3(0) + H*F reversible AlF2*F0 + HF (kH03 = (6.6 +/- 0.5) x 10(4) M-1 s-1). The rates of these exchange reactions increase markedly with increasing F- substitution. Thus, the reactions of AlF2+(aq) were too inert to be detected even on the T1 NMR time scale, while some of the reactions of AlF3(0)(aq) were fast, causing large line broadening. The ligand exchange appears to follow an associative interchange mechanism. The cis-trans isomerization of AlF2+(aq), consistent with octahedral geometry for that complex, is slowed sufficiently to be observed at temperatures around 270 K. Difference between the Al3+/F- system and the much studied Al3+/OH- system are briefly commented on. PMID- 11197007 TI - Uranium(VI) sulfilimine complexes: a new class of nitrogen analogues of the uranyl ion. AB - The compound tetraphenylphosphonium tetrachlorooxo-S,S diphenylsulfiliminatouranium, [Ph4P][UOCl4(NSPh2)], has been prepared in high yield from [Ph4P][UOCl5] and [Ph2S=NSiMe3]. An X-ray structure of this compound shows that the uranium atom has a pseudooctahedral geometry with oxygen and nitrogen atoms in trans positions. The structure of the analogous phosphoriminato complex [Ph4P][UOCl4(NPPh3)] has been determined for comparison. Derivatization of the sulfide group shows that only a limited range of functionalization confers stability toward reduction. The emission spectrum of the first electronic excited state reveals a greatly reduced energy compared with that of the uranyl ion. This red shift in the transition is consistent with the weakening of the U-N bond relative to the U-O bond. PMID- 11197008 TI - Synthesis, structure, and single-crystal EPR study of [Cp(t-Bu3PN)Ti(mu-Cl)]2. AB - The reduction of CpTi(NPt-Bu3)Cl2 with Mg powder in benzene proceeds slowly to give [CpTi(NPt-Bu3(mu-Cl)]2 (1). An X-ray crystallographic study confirmed 1 is a centrosymmetric chloro-bridged dimer in the solid state. A single-crystal EPR study of 1 permitted the determination of the best-fitted values for the diagonal spin Hamiltonian parameters. This appears to be the first EPR single-crystal study of a Ti(III)-Ti(III) dimer. The implications of these data are considered and discussed in light of extended Huckel molecular orbital calculations. PMID- 11197009 TI - Preparation, characterization, and X-ray crystal structures of helical and syndiotactic zinc-based coordination polymers. AB - The reactions of (facac)2Zn.2H2O (facac = 1,1,1,5,5,5-hexafluoroacetylacetonate) with 2,5-bis(4-ethynylpyridyl)furan (1) and 1,2-bis(4-ethynylpyridyl)benzene (2) yield, upon crystallization, coordination polymers. The former polymer, ((facac)2Zn.1)n, has an isotactic, helical structure in the solid state [monoclinic space group P2(1)/n; a = 11.0374(3) A, b = 24.2179(10) A, c = 14.3970(4) A, beta = 92.880(2) degrees; Z = 4]. The latter polymer, ((facac)2Zn.2)n, adopts a syndiotactic structure in the solid state [monoclinic space group P2(1)/n; a = 9.1344(1) A, b = 21.7985(5) A, c = 16.0322(4) A, beta = 99.6680(11) degrees; Z = 4]. The solution structures of the corresponding oligomers have been studied by low-temperature 1H and 19F NMR spectroscopy. Chiral polymers were prepared using the fragment [(+)-tfc]2Zn ((+)-tfc = 3 ((trifluoromethyl)hydroxymethylene)-(+)-camphorate). A linear, zigzag structure was found for ([(+)-tfc]2Zn.1)n [triclinic space group P1; a = 7.4833(2) A, b = 14.1563(5) A, c = 21.21230(5) A, alpha = 78.4440(15) degrees, beta = 81.5644(15) degrees, gamma = 76.4976(13) degrees; Z = 1]. Reaction with tris(4 pyridyl)methanol (3) yielded a homochiral, helical polymer, ([(+)-tfc]2Zn.3)n [monoclinic space group C2; a = 25.0633(12) A, b = 11.8768(7) A, c = 17.1205(9) A, alpha = 90 degrees, beta = 117.954(3) degrees, gamma = 90 degrees; Z = 4]. PMID- 11197010 TI - Synthesis, characterization, and redox behavior of new selenium coronands and of copper(I) and copper(II) complexes of selenium coronands. PMID- 11197011 TI - Synthesis, structure, and magnetic properties of two new ferromagnetic/antiferromagnetic one-dimensional nickel(II) complexes. Magnetostructural correlations. AB - Two new one-dimensional nickel(II) complexes were synthesized and characterized: [Ni(N,N-dimethylethylenediamine)(N3)2] (1) and [Ni(2-aminoethylpyridine)(N3)2] (2). The crystal structures of 1 and 2 were solved. Complex 1 crystallizes in the monoclinic system, space group P2(1)/n with a = 10.569(2) A, b = 7.331(4) A, c = 12.9072(8) A, beta = 111.324(10) degrees, and Z = 4. Complex 2 crystallizes in the monoclinic system, space group P2(1)/c with a = 12.299(5) A, b = 14.307(2) A, c = 12.604(3), beta = 106.72(2) degrees, and Z = 4. The two complexes are similar and may be described as one-dimensional systems with double-azido-bridged ligands in end-to-end and end-on coordination alternatively. The end-on moiety is almost identical for 1 and 2, but the end-to-end moiety is different in each structure: for 1 this part is almost planar but for 2 is nonplanar. In both cases the Ni atoms are situated in similar distorted octahedral environments. The magnetic properties of the two compounds were studied by susceptibility measurements vs temperature. The chi M vs T plots for 1 and 2 show a global antiferromagnetic behavior with a maximum near room temperature for 1 and at very low temperature for 2. J values for 1 and 2 were deduced from the spin Hamiltonian sigma(J1SiSi+1 + J2Si+1Si+2). The computational method was based on the numerical solution for finite systems of increasing size. J values for 1 were J1 = -187 cm 1 and J2 = +77 cm-1 and for 2 J1 = -28 cm-1 and J2 = +73 cm-1. The positive values correspond to end-on azido ligands and the negative values to end-to-end azido ligands. Since the geometries of the [Ni(N3)]2 moieties involving the end on azido ligands are almost the same in the two structures, the ferromagnetic coupling is nearly identical in the two compounds, while the significantly different antiferromagnetic couplings reflect the near planarity of the end-to end Ni2(N3)2 fragment in 1 and its twisted geometry in 2. PMID- 11197012 TI - Unusual 9-->10 rearrangement of the substituted cage carbon in the ferratricarbollide series. Synthesis of the isomeric complexes [2-eta 5-(C5H5)-10 X-closo-2,1,7,10-FeC3B8H10] (where X = H2N, MeHN, Me2N, and ButHN). AB - Treatment of the zwitterionic amine tricarbollides of general formula 7-L-nido 7,8,9-C3B8H10 (1) (where L = Me2HN (1c) and ButH2N (1d)) with [(eta 5 C5H5)Fe(CO)2]2 in refluxing mesitylene resulted in the formation of a mixture of the known compounds [2-(eta 5-C5H5)-9-X-closo-2,1,7,9-FeC3B8H10] (2) (where X = H2N (2a), Me2N (2c), and ButHN (2d)) and a series of new, isomeric ferratricarbollylamines [2-(eta 5-C5H5)-10-X-closo-2,1,7,10-FeC3B8H10] (3) (where X = H2N (3a), Me2N (3c), and ButHN (3d)) in moderate yields. Complexes of type 3 (where X = H2N (3a), MeHN (3b), Me2N (3c), and ButHN (3d)) were also obtained readily by heating complexes of type 2 (where X = H2N (2a), MeHN (2b), Me2N (2c), ButHN (2d), and Bu(t)(Me)N (2e)) at ca. 300 degrees C for 10 min. All the complexes of type 3 contain reactive amine functions in meta positions with respect to the metal center. The observed 9-->10 rearrangement of the substituted cluster carbon is quite unexpected and is believed to result from higher thermodynamic stability of the 10-substituted isomers. The structures of all compounds of type 3 were established by high-field NMR spectroscopy and mass spectrometry, and that of 3d was determined by an X-ray diffraction study. PMID- 11197013 TI - Completion of the series of M2(hpp)4Cl2 compounds from W to Pt: the W, Os, and Pt compounds. AB - The series of M2(hpp)4Cl2 complexes (hpp is the anion of 1,3,4,6,7,8-hexahydro-2H pyrimido[1,2-a]pyrimidine) from M = W to M = Pt has been completed by the preparation and characterization of those with M = W, Os, and Pt. W(hpp)4Cl2 (1) has a W-W distance of 2.250(2) A, is diamagnetic, and can be assigned a W-W triple bond based on a sigma 2 pi 4 electron configuration. Os2(hpp)4Cl2 (2) has an Os-Os distance of 2.379(2) A and displays a temperature-independent paramagnetism. It can be assigned a sigma 2 pi 4 delta 2 delta*2 configuration. Pt2(hpp)4Cl2 has a Pt-Pt distance of 2.440(1) A and is diamagnetic. A bond order of 1, based on a configuration in which only the sigma* orbital is empty, is consistent with these data. PMID- 11197014 TI - Lowest electronic excited states of platinum(II) diimine complexes. AB - Absorption and emission spectra of Pt(diimine)L2 complexes (diimine = 2,2' bipyridine (bpy) or 4,4'-dimethyl-2,2'-bipyridine (dmbpy); L = pyrazolate (pz-), 3,5-dimethylpyrazolate (dmpz-), or 3,4,5-trimethylpyrazolate (tmpz-)) have been measured. Solvent-sensitive absorption bands (370-440 nm) are attributed to spin allowed metal-to-ligand charge-transfer (1MLCT) transitions. As solids and in 77 K glassy solution, Pt(bpy)(pz)2 and Pt(dmbpy)(pz)2 exhibit highly structured emission systems (lambda max approximately 494 nm) similar to those of the diprotonated forms of these complexes. The highly structured bands (spacings 1000 1400 cm-1) indicate that the transition originates in a diimine-centered 3(pi- >pi*) (3LL) excited state. The intense solid-state and 77 K glassy solution emissions from 3MLCT[d(Pt)-->pi*(bpy)] excited states of complexes with dmpz- and tmpz- ligands occur at longer wavelengths (lambda max = 500-610 nm), with much broader vibronic structure. These findings are consistent with increasing electron donation of the pyrazolate ligands, leading to a distinct crossover from a lowest 3LL to a 3MLCT excited state. PMID- 11197015 TI - Polysulfide anions II: structure and vibrational spectra of the S4(2-) and S5(2-) anions. Influence of the cations on bond length, valence, and torsion angle. AB - The influence of the cations on bond length, valence, and torsion angle of S4(2-) and S5(2-) anions was examined in a series of solid alkali tetra- and pentasulfides by relating their Raman spectra to their known X-ray structures through a force-field analysis. The IR and Raman spectra of BaS4.H2O and the Raman spectra of (NH4)2S4.nNH3, gamma-Na2S4, and delta-Na2S5 are presented. The similarity of spectra of gamma-Na2S4 with those of BaS4.H2O suggests similar structures of the S4(2-) anions in these two compounds with a torsion angle smaller than 90 degrees. The variations of SS bond length, SSS valence angle, and dihedral angle of Sn2- anions are related to the polarization of the lone pair and electronic charge of the anion by the electric field of the cations. A correlation between the torsion angle and the SSS valence angle is shown as that previously reported between the length of the bond around which the torsion takes place and the dihedral angle value. These geometry changes are explained by the hyperconjugation concept and the electron long-pair repulsion. PMID- 11197016 TI - Binding and redox properties of iron(II) bonded to an oxo surface modeled by calix[4]arene. AB - The syntheses of the parent compounds [(p-Bu(t)-calix[4]-(O)2(OR)2)Fe-L] [R = Me, L = THF, 5; R = Bu(n), L = THF, 6; R = PhCH2, L = THF, 7; R = SiMe3, L = none, 8] have been performed by reacting the protonated form of the dialkylcalix[4]arene with [Fe2Mes4] [Mes = 2,4,6-Me3C6H2]. All of them undergo one-electron oxidative functionalization. By use of different oxidizing agents, the following iron(III) derivatives have been obtained: [(p-Bu(t)-calix[4]-(O)2(OR)2)Fe-X] [X = Cl, R = Me, 9; X = I, R = Me, 10] and [(p-Bu(t)-calix[4]-(O)2(OR)2)2Fe2(mu-X] [X = O, R = Me, 11; X = O, R = Bu(n), 12; X = S, R = Me, 13], 9 and 10 being particularly appropriate for a further functionalization of the metal. The last three display typical antiferromagnetic behavior [J = -78.6 cm-1, 11; J = -64.1 cm-1, 13]. In the case of 7 and 8, the reaction with O2 led to the dealkylation of one of the alkoxo groups, with the formation of a dimeric iron(III) derivative ([mu-p-Bu(t) calix[4]-(O)3(OR))2Fe2] [R = PhCH2, 14; R = SiMe3, 15] [J = -9.8 cm-1]. The reaction of the parent compounds with ButNC and diazoalkanes led to the formation of [Fe=C] functionalities supported by a calix[4]arene oxo surface. The following compounds have been isolated and characterized: ([p-Bu(t)-calix[4] (O)2(OR)2)Fe=CNBut] [R = SiMe3, 16, nu CN = 2175 cm-1], ([p-Bu(t)-calix[4] (O)2(OR)2)Fe=CPh2] [R = Me, 17; R = PhCH2, 18; R = SiMe3, 19]. The three carbene complexes 17-19 display quite an unusual high-spin state, which is a consequence of the formation of a weak pi interaction between the metal and the carbene carbon, as confirmed by the extended Huckel calculations. The carbene functionality has been removed from the iron center in the reaction with O2 and HCl. The proposed structures have been supported by X-ray analyses of complexes 8, 9, 12, 14, 16, 17, and 19. PMID- 11197017 TI - General-acid-catalyzed reactions of hypochlorous acid and acetyl hypochlorite with chlorite ion. AB - The rate of oxidation of ClO2- by HOCl is first order in each reactant and is general-acid catalyzed. In the initial steps of the proposed mechanism, a steady state intermediate, HOClOClO-, forms (k1 = 1.6 M-1 s-1) and undergoes general acid (HA)-catalyzed reactions (k2HA) to generate a metastable intermediate, ClOClO. Values of k2HA/k-1 are 1.6 x 10(4) M-1 (H3O+), 20 M-1 (HOAc), and 8.5 M-1 (H2PO4-). Subsequent competitive reactions of ClOClO with ClO2- (k3) to give 2ClO2 and with OH- (k4OH) and other bases (k5B) to give ClO3- are very rapid. The relative yields of these products give k4OH/k3 = 1.3 x 10(5), k5HPO4/k3 = 0.20, and k5OAc/k3 = 0.06. At low pH and low buffer concentrations, the apparent yield of ClO2, based on 2ClO2 per initial HOCl, reaches 140%. This anomaly is attributed to the induced disproportionation of ClO2- by ClOClO to give ClO3- and additional HOCl. A highly reactive intermediate, ClOCl(O)OClO-, is proposed that can undergo Cl-O bond cleavage to give 2ClO2 + Cl- via one path and ClO3- + 2HOCl via another path. The additional HOCl recycles in the presence of excess ClO2- to give more ClO2. Ab initio calculations show feasible structures for the proposed reaction intermediates. Acetic acid has a second catalytic role through the formation of acetyl hypochlorite, which is much more reactive than HOCl in the transfer of Cl+ to ClO2- to form ClOClO. PMID- 11197018 TI - An EPR and 1H NMR active mixed-valence manganese (III/II/III) trinuclear compound. AB - A mixed-valence Mn(III)-Mn(II)-Mn(III) trinuclear complex of stoichiometry MnIIIMnIIMnIII(Hsaladhp)2(Sal)4.2CH3CN (1), where H3saladhp is a tridentate Schiff-base ligand, has been structurally characterized with X-ray crystallography. The Mn(III)Mn(II)Mn(III) angles are strictly 180 degrees as required by crystallographic inversion symmetry. The complex is valence-trapped with two terminal Mn(III) ions in a distorted square pyramidal geometry. The Mn(III)...Mn(II) separation is 3.495 A. The trinuclear complex shows small antiferromagnetic exchange J coupling. The magnetic parameters obtained from the fitting procedure in the temperature range 10-300 K are J1 = -5.7 cm-1, g = 2.02, zJ = -0.19 cm-1, and R = 0.004. The EPR spectrum was obtained at 4 K in CHCl3 and in tetrahydrofuran glasses. The low-field EPR signal is a superposition of two signals, one centered around g = 3.6 and the other, for which hyperfine structure is observed, centered around g = 4.1 indicating an S = 3/2 state. In addition, there is a 19-line signal at g = 2.0. The multiline signal compares well with that observed for the S2 or S0* states of the oxygen-evolving complex. 1H NMR data reveal that the trinuclear compound keeps its integrity into the CHCl3 solution. Crystal data for complex 1: [C54H52N4O18Mn3], M = 1209.82, triclinic, space group P1, a = 10.367(6) A, b = 11.369(6) A, c = 13.967(8) A; alpha = 112.56(1) degree, beta = 93.42(2) degrees, gamma = 115.43(1) degree, Z = 1. PMID- 11197019 TI - New calcium germanium nitrides: Ca2GeN2, Ca4GeN4, and Ca5Ge2N6. AB - We report three new calcium germanium nitrides synthesized as crystals from the elements in sealed niobium tubes at 760 degrees C using liquid sodium as a growth medium. Black Ca2GeN2 is isostructural with the previously reported strontium analogue. It is tetragonal P4(2)/mbc (no. 135) with a = 11.2004(8) A, c = 5.0482(6) A, and Z = 8. It contains GeN2(4-) units which have 18 valence electrons, and consequently are bent, like the isoelectronic molecule SO2. In contrast, clear, orange Ca4GeN4 with fully oxidized germanium contains isolated GeN4(8-) tetrahedra and is monoclinic P2(1)/c (no. 14) with a = 9.2823(8) A, b = 6.0429(5) A, c = 11.1612(9) A, beta = 116.498(6) degrees, and Z = 4. Clear, colorless Ca5Ge2N6, also with fully oxidized germanium, contains infinite chains, 1 infinity[GeN2N2/2(5-)], of corner-sharing tetrahedra similar to those found in pyroxenes. However, the precise structure of this latter phase has not yet been determined because of twinning problems. PMID- 11197020 TI - Lanthanide chalcogenolate complexes: synthesis and crystal structures of the isoleptic series [Sm(TpMe,Me)2ER] (E = O, S, Se, Te; TpMe,Me = tris-3,5 dimethylpyrazolylborate). AB - A series of lanthanide complexes containing a chalcogenolate ligand supported by two TpMe,Me (tris-3,5-dimethylpyrazolylborate) groups has been prepared and crystallized and provides direct comparisons of bonding to hard and soft ligands at lanthanide centers. Reaction of [Sm(TpMe,Me)2Cl] with NaOR (R = Ph, Ph-Bu(t)) gives [Sm(TpMe,Me)2OR] (1a and 1b, respectively) in good yields. Reductive cleavage of dichalcogenides by samarium(II) was used to prepare the heavier congeners. Complexes of the type [Sm(TpMe,Me)2ER] for E = S, R = Ph (2a), E = S, R = Ph-4-Me (2b), E = S, R = CH2Ph (2c), E = Se, R = Ph (3a), E = Se, R = Ph-4 Bu(t) (3b), E = Se, R = CH2Ph (3c), and E = Te, R = Ph (4) have been prepared together with the corresponding complexes with TpMe,Me,4-Et as ancillary. The X ray crystal structures of 1b, 2b, 3a, 3b, and 4 have been determined. The crystal of 1b (C40H57B2N12OSm.C7H8) was monoclinic, P2(1)/c, a = 10.6845(6) A, b = 18.5573(11) A, c = 24.4075(14) A, beta = 91.616(2) degrees, Z = 4. The crystal of 2b (C37H51B2N12SSm) was monoclinic, P2(1)/n, a = 15.0154(9) A, b = 13.1853(8) A, c = 21.1254(13) A, beta = 108.628(2) degrees, Z = 4. The crystal of 3a (C36H49B2N12SeSm.C7H8) was triclinic, P1, a = 10.7819(6) A, b = 19.3011(10) A, c = 23.0235(12) A, alpha = 79.443(2) degrees, beta = 77.428(2) degrees, gamma = 89.827(2) degrees, Z = 4. The crystal of 3b (C40H57B2N12SeSm) was triclinic, P1, a = 10.1801(6) A, b = 10.2622(6) A, c = 23.4367(14) A, alpha = 88.313(2) degrees, beta = 86.268(2) degrees, gamma = 62.503(2) degrees, Z = 2. The crystal of 4 (C36H49B2N12TeSm.C7H8) was monoclinic, P2(1)/c, a = 18.7440(10) A, b = 10.3892(6) A, c = 23.8351(13) A, beta = 94.854(2) degrees, Z = 4. The compounds form an isoleptic series of seven-coordinate complexes with terminal chalcogenolate ligands. Examination of 1b and other crystallographically characterized lanthanide alkoxides suggests that there is little correlation between bond angle and bond length. The structures of 3a and 3b, however, contain molecules in which one of the pyrazolylborate ligands undergoes a major distortion arising from twisting around a B-N bond so as to give an effectively eight-coordinate complex with pi-stacking of the phenyl group with one pyrazolyl ring. These distortions shed light on the fluxionality of these systems. PMID- 11197021 TI - M+(12-crown-4) supramolecular cations (M+ = Na+, K+, Rb+, and NH4+) within Ni(2 thioxo-1,3-dithiole-4,5-dithiolate)2 molecular conductor. AB - Monovalent cations (M+ = Na+, K+, Rb+, and NH4+) and 12-crown-4 were assembled to new supramolecular cation (SC+) structures of the M+(12-crown-4)n (n = 1 and 2), which were incorporated into the electrically conducting Ni(dmit)2 salts (dmit = 2-thioxo-1,3-dithiole-4,5-dithiolate). The Na+, K+, and Rb+ salts are isostructural with a stoichiometry of the M+(12-crown-4)2[Ni(dmit)2]4, while the NH4+ salt has a stoichiometry of NH4+(12-crown-4)[Ni(dmit)2]3(CH3CN)2. The electrical conductivities of the Na+, K+, Rb+, and NH4+ salts at room temperature are 7.87, 4.46, 0.78, and 0.14 S cm-1, respectively, with a semiconducting temperature dependence. The SC+ structures of the Na+, K+, and Rb+ salts have an ion-capturing sandwich-type cavity of M+(12-crown-4)2, in which the M+ ion is coordinated by eight oxygen atoms of the two 12-crown-4 molecules. On the other hand, the NH4+ ion is coordinated by four oxygen atoms of the 12-crown-4 molecule. Judging from the M(+)-O distances, thermal parameters of oxygen atoms, and vibration spectra, the thermal fluctuation of the Na+(12-crown-4)2 structure is larger than those of K+(12-crown-4)2 and Rb+(12-crown-4)2. The SC+ unit with the larger alkali metal cation gave a stress to the Ni(dmit)2 column, and the SC+ structure changed the pi-pi overlap mode and electrically conducting behavior. PMID- 11197022 TI - Synthesis of a ligand based upon a new entry into the 3-hydroxy-N-alkyl-2(1H) pyridinone ring system and thermodynamic evaluation of its gadolinium complex. AB - The synthesis of a new, more water soluble derivative of TREN-Me-3,2-HOPO (tris[(3-hydroxy-1-methyl-2-oxo-1,2- didehydropyridine-4-carboxamido)ethyl]amine) is presented. The synthesis starts with the condensation reaction of (N methoxyethylamino)acetonitrile hydrochloride and oxalyl chloride to give 3,5 dichloro-N-(methoxyethyl)-2(1H)-pyrazinone. The 3-position is readily substituted with a benzyloxy group, and the pyrazinone is converted to ethyl 3-(benzyloxy)-N (methoxyethyl)-2(1H)-pyridinone-4-carboxylate by a Diels-Alder cycloaddition with ethyl propiolate. Basic deprotection of the ester followed by activation, coupling to tren, and acidic deprotection of the benzyl groups gives the ligand TREN-MOE-3,2-HOPO (tris[(3-hydroxy-1-(methoxyethyl)- 2-oxo-1,2-didehydropyridine 4-carboxamido)ethyl]amine). The gadolinium complex of TREN-MOE-3,2-HOPO was prepared by metathesis, starting from gadolinium chloride. The solubility of the new metal complex is significantly enhanced. The four protonation constants (determined by potentiometry) for TREN-MOE-3,2-HOPO (log Ka1 = 8.08, log Ka2 = 6.85, log Ka3 = 5.81, log Ka4 = 4.98) are virtually identical to those reported for the parent ligand. The stability constants for the gadolinium complex of TREN MOE-3,2-HOPO determined by potentiometry (log beta 110 = 19.69(2), log beta 111 = 22.80(2)) and by spectrophotometry (log beta 110 = 19.80(1), log beta 111 = 22.88(1), log beta 112 = 25.88(1)) differ slightly from those for the parent ligand; this follows from a change in the complexation model in which a new diprotonated species, [Gd(TREN-MOE-3,2-HOPO)(H)2]2+, was included. The presence of this extra species was demonstrated by factor analysis, comparison of spectral data, and nonlinear least-squares refinement. Significant formation of this species is observed between pH 3 and pH 1.5. PMID- 11197023 TI - Kinetics of silicate exchange in alkaline aluminosilicate solutions. AB - In strongly alkaline aqueous KOH solutions containing SiIV in large excess over AlIII, the kinetics of exchange of monomeric silicate with small acyclic aluminosilicate solute species is much more rapid than with either cyclic aluminosilicates or any all-silicate anions. Selective inversion recovery 29Si NMR studies of homogeneous solutions of stoichiometric composition 3.0 mol kg-1 of SiO2, 0.1 mol kg-1 of Al2O3, and 8.0 mol kg-1 of K2O in 60-75% D2O gave rate constants of 2.0 +/- 0.2 kg mol-1 s-1 and 17 +/- 4 s-1 for the forward and reverse reactions of monomeric silicate with (HO)3AlOSiOn(OH)(3-n)(n+1)- (n = 2 or 3) at 0 degree C. These rate constants are more than 10(4)-fold faster than those extrapolated from 60 to 90 degrees C for comparable reactions of silicate anions. The greater lability of acyclic aluminate centers relative to silicate is ascribed partly to the availability of HO- groups for condensation reactions on Al and mainly to the ease of expansion of the coordination number of AlIII beyond 4. The latter attribute is diminished when AlIII is constrained to be tetrahedral in cyclic structures. With respect to the mechanism of formation of zeolites from alkaline aqueous media, it is suggested that small, labile AlOSi units add rapidly to growing zeolitic structures "on demand", whereas the more kinetically inert cage or ring structures cannot. This would explain why a silicate or aluminosilicate structure that is dominant among solute species at equilibrium in the presence of a particular cation may bear little or no geometric relation to the zeolitic framework promoted kinetically by that same cation. PMID- 11197024 TI - EPR and ligand field studies of iron superoxide dismutases and iron-substituted manganese superoxide dismutases: relationships between electronic structure of the active site and activity. AB - The problem of metal selectivity of iron/manganese superoxide dismutases (SODs) is addressed through the electronic structures of active sites using electron paramagnetic resonance and ligand field calculations. Studies of wild-type iron(III) SOD (FeSOD) from Escherichia coli and from Methanobacterium thermoautotrophicum and iron-substituted manganese(III) SOD (Fe(sub)MnSOD) from E. coli and from Serratia marcescens are reported. EPR spectroscopy of wild-type enzymes shows transitions within all three Kramers doublets identified by their g values. From the temperature dependence of the observed transitions, the zero field splitting is found to be negative, D = -2 +/- 0.2 cm-1. The electronic structure is typical of a distorted trigonal bipyramid, all the EPR features being reproduced by ligand field analysis. This unique and necessary electronic structure characterizes wild-type enzymes whatever their classification from the amino acid sequence into iron or manganese types, as E. coli FeSOD or M. thermoautotrophicum FeSOD. In iron-substituted manganese SODs, reduced catalytic activity is found. We describe how inhomogeneity of all reported substituted MnSODs might explain the activity decrease. EPR spectra of substituted enzymes show several overlapping components. From simulation of these spectra, one component is identified which shares the same electronic structure of the wild type FeSODs, with the proportion depending on pH. Ligand field calculations were performed to investigate distortions of the active site geometry which induce variation of the excitation energy of the lowest quartet state. The corresponding coupling between the ground state and the excited state is found to be maximum in the geometry of the native SODs. We conjecture that such coupling should be considered in the electron-transfer process and in the contribution of the typical electronic structure of FeSOD to the activity. PMID- 11197025 TI - Reactions of the dirhenium(II) complexes Re2X4(mu-dppm)2 (X = Cl, Br; dppm = Ph2PCH2PPh2) with isocyanides. 21. A comparison with the complexes Re2Cl4(mu dppE)2 and Re2Cl4(mu-dcpm)2 (dppE = Ph2PC(=CH2)PPh2; dcpm = Cy2PCH2PCy2) and the structural characterization of complexes of the types Re2Cl4(mu-LL)2(CNR), Re2Cl4(mu-LL)2(CNR)2, and [Re2Cl3(mu-LL)2(CNR)3]+ (LL = dppm, dppE, dcpm; R = t Bu, Xyl). AB - A study of the reactions between the triply bonded dirhenium(II) complexes Re2Cl4(mu-LL)2, where LL = Ph2PCH2PPh2 (dppm), Ph2PC(=CH2)PPh2 (dppE), or Cy2PCH2PCy2 (dcpm), with the isocyanides t-BuNC and XylNC (Xyl = 2,6 dimethylphenyl) show that complexes of the type Re2Cl4(mu-LL)2(CNR), Re2Cl4(mu LL)2(CNR)2, and [Re2Cl3(mu-LL)2(CNR)3]+ are formed sequentially. Several of these have been structurally characterized by X-ray crystallography: Re2Cl4(mu dppm)2(CNXyl) (2), Re2Cl4(mu-dcpm)2(CNXyl) (11), Re2Cl4(mu-dppE)2(CN-t-Bu)2 (6), Re2Cl4(mu-dcpm)2(CN-t-Bu)2 (12), and [Re2Cl3(mu-dppE)2(CN-t-Bu)3]Cl (7). Complex 2 has an A-frame-like structure with a single mu-Cl bridging ligand, whereas for 11 the structure is like that of 2 but without this bridge, viz., Cl2Re(mu dppm)2ReCl2(CNXyl) with a Re-Cl bond approximately collinear with Re identical to Re. The symmetrical complexes 6 and 12 are essentially isostructural and have an anti-arrangement of the two t-BuNC ligands. Complex 7 has the open bioctahedral structure [(t-BuNC)2ClRe(mu-dppE)2ReCl2(CN-t-Bu)]+, which is quite different from that of the edge-sharing bioctahedron found in salts of the [Re2Cl3(mu dppm)2(CNXyl)3]+ cation and its neutral congener Re2Cl3(mu-dppm)2(CNXyl)3; preliminary crystallographic data for the latter compound show the structure to be (XylNC)ClRe(mu-Cl)(mu-CNXyl)(mu-dppm)2ReCl(CNXyl) with an all-cis arrangement of XylNC ligands. The Re-Re bond distances of 2, 6, 7, 11, and 12 occur in the range 2.289-2.380 A and are consistent in all instances with the retention of a Re identical to Re bond, albeit weakened by some degree of Re-->CNR(pi*) back bonding. PMID- 11197026 TI - Self-assembling molecular wires of halogen-bridged platinum complexes in organic media. Mesoscopic supramolecular assemblies consisting of a mixed valent Pt(II)/Pt(IV) complex and anionic amphiphiles. AB - A novel class of supramolecular assemblies in organic media consisting of a molecular wire of a halogen-bridged platinum complex [Pt(en)2][PtCl2(en)2]4+ (en = 1,2-diaminoethane) and anionic amphiphiles is developed. When double-chained phosphates or sulfonates are employed, the resultant [Pt(en)2][PtCl2(en)2](4+) lipid complexes displayed intervalence charge transfer (CT) absorption bands in the crystalline state. They are soluble in organic solvents because of the amphiphilic superstructure, in which the solvophobic one-dimensional platinum complex is surrounded by solvophilic alkyl chains. CT absorption bands of halogen bridged linear complexes are maintained in organic media, with varied colors that depend on the chemical structure of constituent amphiphiles. Monoalkylated phosphates failed to form colored, halogen-bridged ternary complexes probably because of their coordination to the axial position of PtII(en)2. Formation of mesoscopic supramolecular assemblies in organic media was confirmed for the [Pt(en)2][PtCl2(en)2] complexes by electron microscopy. Interestingly, a supramolecular complex consisting of dihexadecyl sulfosuccinate and [Pt(en)2][PtCl2(en)2]4+ displayed clear, indigo solutions that are distinct from the yellow color observed for those of [Pt(en)2][PtCl2(en)2]/dialkyl phosphate complexes. The indigo color of the former complex disappeared upon heating the solution to 60 degrees C, whereas it reappeared reversibly by cooling the solution to room temperature. In electron microscopy, rodlike nanostructures with a minimum width of 18 nm and lengths of 700-1700 nm were observed after cooling, though not at elevated temperatures. Apparently, the lipid [Pt(en)2][PtCl2(en)2]4+ complex undergoes reversible dissociation and reassembly processes in chloroform, and it becomes better dispersed after the reassembling process. The present finding opens a general route to solution chemistry of low dimensional inorganic complexes and enables rational design and control of self assembling inorganic molecular wires. PMID- 11197027 TI - Crystal structure of the molecular addition compound diphenylchloroborane.tetrahydrofuran. PMID- 11197028 TI - Synthesis and characterization of a homoleptic thiolate complex of titanium(IV). PMID- 11197029 TI - Unusual redox state dependent fermi resonances in the infrared spectra of trinuclear ruthenium clusters with isocyanide ligands. PMID- 11197030 TI - Self-association in gold chemistry: a tetragold(I) complex linked by both aurophilic and hydrogen bonding. PMID- 11197031 TI - Neighborhood views on the definition and etiology of child maltreatment. AB - OBJECTIVE: The purpose of this study, as part of a larger study on neighborhoods and child maltreatment, was to determine how parents residing in neighborhoods with differing profiles of risk for child maltreatment reports defined child abuse and neglect and viewed its etiology. METHOD: Parents (n = 400) were systematically selected from neighborhoods (n=20) with different profiles of risk for child maltreatment report rates. As part of a larger interview, parents were asked to generate lists of behaviors that they would define as child abuse and neglect and to rate 13 etiological factors on a 10 point scale as to their contribution to the occurrence of child maltreatment. RESULTS: While there were differences in definitional emphases, with African-American parents including behaviors of neglect and European-American parents including behaviors of physical abuse, there was marked congruence on the catalogue of behaviors that parents would define as child abuse and neglect. Four factors were identified that explained almost two-thirds of the variance in parents' etiological explanations: poverty and family disruption, substance abuse and stress; lack of moral and family values; and individual pathology. These factors were related to neighborhood conditions, individual perceptions of neighborhood and individual characteristics. CONCLUSIONS: Community-based programs aimed at preventing or ameliorating child maltreatment must have at their very core an understanding of how populations being served define child maltreatment and why they believe that it occurs. PMID- 11197032 TI - Disciplining children: characteristics associated with the use of corporal punishment. AB - OBJECTIVE: To evaluate the Social Situational Model of Family Violence through an examination of characteristics associated with the use of ordinary and severe corporal punishment as measured by the Parents-Child Conflict Tactics Scales. METHOD: Logistic Regression used to examine the validity of the model using data from a national sample conducted by the Gallup Organizations. RESULTS: Those with fewer resources (lower income, lower educational attainment) were more likely to be use severe corporal punishment. In addition, those who had been more likely to be socialized into the use of violence were also more likely to use severe corporal punishment. CONCLUSIONS: The social situational model of family violence was supported suggesting that increased efforts be made to give these parents the resources they need to implement alternative discipline strategies. PMID- 11197033 TI - Maternal infanticides in Fiji. AB - OBJECTIVE: This essay contributes to the cross-cultural literature on childhood homicides by examining 16 infanticidal homicides that occurred in Fiji over an 11 year period. The results are compared with infanticide studies conducted in other societies. METHOD: Official police data recorded in a Homicide and Manslaughter register are analyzed. These are supplemented by newspaper reports of infanticides and semi-structured interviews conducted with key criminal justice and medical personnel intimately associated with infanticide cases. RESULTS: The findings show that most infanticide defendants were young, poor, Fijian, with little formal education, living with nonparental kin at the time of the crime. The infanticides were precipitated by unwanted pregnancies brought on by nonmarital and extramarital sex. Pregnancy is carried to full gestation without knowledge of family, friends and neighbors of offenders and the infant is killed immediately following birth. CONCLUSIONS: The current findings demonstrate that the patterns of maternal infant killings in Fiji are congruous in many significant ways with those in advanced industrialized societies. It is concluded that additional research in non-Western, nonindustrialized nations is imperative to contribute to the development of sound conclusions about, and remedies for infanticide. PMID- 11197034 TI - [Psychosocial aspects of infanticide in black Africa: the case of Senegal]. AB - OBJECTIVE: Following the example of Senegal, this study had two main objectives. First: Ring the alarm bell about the large number of infanticides in a country where people usually consider a child as a treasure. Second: Highlight the deep motivations which may induce an African woman to kill her child. METHOD: The author examined psychiatric experts reports about crimes and varied offenses acquired from Fann University Hospital in Dakar during a 27 year period, from January 1968 to December 1994. RESULTS: For a total number of 164 reports, 33 or 20% concerned infanticides. This underlines the importance of the phenomenon. Mental pathology appeared in two cases (3%) but 97% were supposed to be mentally healthy. CONCLUSION: These results suggest that social and cultural reasons more than medical ones explain the occurrence of infanticides. It seems that it is under the pressure of social and cultural motivations that women and especially young mothers, depreciate becoming a mother. PMID- 11197035 TI - Children involved in bullying at elementary school age: their psychiatric symptoms and deviance in adolescence. An epidemiological sample. AB - OBJECTIVE: This study investigated psychiatric symptoms and deviance at the age of 15 years among children involved in bullying at the age of 8 years or at the age of 12 years. Furthermore, the relationships between involvement in bullying at the age of 8 years, concurrent psychiatric deviance, and later psychiatric deviance were studied. METHOD: Questionnaires filled in by the parents, teachers and children themselves were used to reveal psychiatric symptoms and deviance. RESULTS: Children involved in bullying, in particular those who were bully victims at early elementary school age and those who were victims in their early teens, had more psychiatric symptoms at the age of 15 years. The probability of being deviant at the age of 15 years was higher among children involved in bullying at the age of 8 or 12 years than among non-involved children. When concurrent psychiatric deviance was taken into account, involvement in bullying increased the probability of teacher-defined deviance at the age of 15 years. CONCLUSION: Bullying experiences are connected not only to concurrent psychiatric symptoms but also to future psychiatric symptoms. Furthermore, the probability of being deviant in adolescence is increased if the child has been involved in bullying at elementary school age. PMID- 11197036 TI - Sexual abuse during childhood and adolescence among Nicaraguan men and women: a population-based anonymous survey. AB - AIMS: The objective was to describe experiences of sexual abuse occurring before 19 years of age among men and women in Leon, Nicaragua and to explore the possible association to later sexual risk behavior. METHOD: A sub-sample of literate urban men and women 25-44 years of age was selected from a representative sample of households in Leon. After an invitation to a public health event, 154 men (53% of the invited) and 213 women (66% of those invited) participated in giving written answers to an anonymous questionnaire. RESULTS: Twenty percent of men and 26% of women reported that they had experienced sexual abuse. Women had been victims of attempted or completed rape twice as often as men, 15% as compared to 7%. Thirty-three percent of the abuse towards boys and 66% of the abuse towards girls was committed by family members. Women who had experienced attempted or completed rape were more likely to later have had a higher number of sexual partners compared to non-abused or moderately abused women. CONCLUSIONS: Sexual abuse of children and adolescents of both sexes is common in Nicaragua. The results underscore the urgent need to address this serious problem more openly, and to make more resources available for the prevention of sexual abuse and for support to victims. PMID- 11197037 TI - Child on child sexual abuse: psychological perspectives. AB - OBJECTIVE: This study describes the emotional and behavioral responses of children who have been sexually victimized by juveniles (CC) 17 years of age and younger compared to child victims of adults (CA) 18 years of age and older. METHOD: A total sample of N = 194 children and adolescents participated in the study, with 26% (n = 51) comprising CC and 74% (n = 143) encompassing CA. The mother/caretaker was administered a demographic form, Achenbach's Child Behavior Checklist (CBCL), and the Family Assessment Measure (FAM-P). The child was given the Family Assessment Measure (FAM-C) and the Trauma Symptom Checklist for Children (TSCC). The clinician completed the Parental Reaction to Incest Disclosure Scale (PRIDS). RESULTS: No differences were found between the two groups for the type of sexual abuse, penetration, or the use of force. CC were younger and more likely to be males who were abused in a school setting, home, or a relative's home by a sibling or a non-related male. CC endorsed clinically significant sexual preoccupations and manifested borderline clinically significant symptomatology. CONCLUSIONS: Children victimized by other children manifested elevated levels of emotional and behavioral problems and were not significantly different from those who had been sexually abused by adults. PMID- 11197038 TI - The use of telemedicine in child sexual abuse evaluations. AB - OBJECTIVE: To describe the advantages, disadvantages and current status of child abuse consultations conducted through telemedicine networks. METHOD: The results of a telephone survey of seven statewide telemedicine networks are reported and discussed with respect to goals, funding, technical support and expertise, infrastructure, and extent of use. Quality assurance and liability issues concerning telemedicine child abuse consultations are also reviewed. RESULTS: The goals of telemedicine networks in child abuse are to provide (1) expertise to less experienced clinicians primarily in rural areas; (2) a method for peer review and quality assurance to build consensus of opinions particularly in sexual abuse cases; and (3) support for professionals involved in an emotionally burdensome area of pediatrics. Problems encountered by existing networks include: (1) funding for equipment and reimbursement for consultation; (2) consistent technical support: (3) clinician lack of technical expertise, knowledge, or motivation; and (4) lack of network infrastructure. Legal considerations include licensure exemptions for consulting across state lines, potential for malpractice, patient confidentiality and security of images forwarded over modem lines, and liability of the equipment, consulting site, and the consultant in criminal proceedings. CONCLUSIONS: Telemedicine consultations offer a unique opportunity to raise the standard of care in child abuse evaluations, but success depends on clinician motivation, appropriate infrastructure, and ongoing funding and technical support. PMID- 11197039 TI - Emotional responses to child sexual abuse: a comparison between police and social workers in Hong Kong. AB - OBJECTIVE: Research on specific emotional responses of professionals to child sexual abuse (CSA), other than the overwhelming feeling, is currently lacking in the child welfare literature. This study examines the initial responses to CSA of police and social workers in Hong Kong. METHOD: Based on their recall of the first child sexual abuse incident, 28 police officers and 86 social workers from 10 training sessions on child sexual abuse in Hong Kong indicated how strong they felt about their emotions in 10 categories of 37 responses. RESULTS: Among the 37 emotional responses, police and social workers showed significant differences in only seven responses: (1) embarrassment with the perpetrator; (2) ambivalence about rescuing the child or preserving the family; (3) fear of being inadequate in handling the situation; (4) titillation in response to our involuntary physiological responses to words and descriptions of sex acts; (5) feelings of revenge because the behavior was bad or immoral; (6) empathy with the child's condition; and (7) ambivalence about helping or punishing the perpetrator. In both groups, "anger at the perpetrator" and "empathy with the child's condition" were the most strongly felt emotions. CONCLUSIONS: Although these two professional groups were not significantly different in most of the emotional responses to their first child sexual abuse incidents, police were more likely to have ambivalent and revenge feelings, while social workers were more likely to have discomfort feelings. Limitations of this research project include sampling procedure, self-report biases, and effect of training. PMID- 11197040 TI - Childhood disciplinary experiences reported by adults with craniofacial anomalies. PMID- 11197041 TI - Enhancing children's narratives in investigative interviews. AB - OBJECTIVE: To illustrate the amount of detail that can be elicited from alleged abuse victims using open-ended prompts by closely examining forensic interviews of a 5-year-old and a 15-year-old. METHOD: Interview prompts in the substantive sections of two forensic interviews were characterized as invitations, cued invitations. directive or option-posing, and the number of details they each elicited was tabulated. RESULTS: In both interviews, open-ended prompts predominated and were distributed throughout the substantive phases of the interviews. Most of the information obtained was elicited using open-ended prompts, which remained equivalently effective throughout the interviews. Reconstruction of the children's accounts illustrated how successive prompts continued to elicit information. CONCLUSION: Well-framed open-ended prompts, including those that use details provided by the child as cues, elicit narrative accounts from children of all ages. Because such information is more likely to be accurate, investigators are urged to rely more extensively on open-ended prompts. PMID- 11197042 TI - Community acquired acute Helicobacter pylori gastritis. PMID- 11197043 TI - Chronic hepatitis B virus infection in Asian countries. AB - Of the estimated 50 million new cases of hepatitis B virus (HBV) infection diagnosed annually, 5-10% of adults and up to 90% of infants will become chronically infected, 75% of these in Asia where hepatitis B is the leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). In Indonesia, 4.6% of the population was positive for HBsAg in 1994 and of these, 21% were positive for HBeAg and 73% for anti-HBe; 44% and 45% of Indonesian patients with cirrhosis and HCC, respectively, were HBsAg positive. In the Philippines, there appear to be two types of age-specific HBsAg prevalence, suggesting different modes of transmission. In Thailand, 8-10% of males and 6-8% of females are HBsAg positive, with HBsAg also found in 30% of patients with cirrhosis and 50-75% of those with HCC. In Taiwan, 75-80% of patients with chronic liver disease are HBsAg positive, and HBsAg is found in 34% and 72% of patients with cirrhosis and HCC, respectively. In China, 73% of patients with chronic hepatitis and 78% and 71% of those with cirrhosis and HCC, respectively, are HBsAg positive. In Singapore, the prevalence of HBsAg has dropped since the introduction of HBV vaccination and the HBsAg seroprevalence of unvaccinated individuals over 5 years of age is 4.5%. In Malaysia, 5.24% of healthy volunteers, with a mean age of 34 years, were positive for HBsAg in 1997. In the highly endemic countries in Asia, the majority of infections are contracted postnatally or perinatally. Three phases of chronic HBV infection are recognized: phase 1 patients are HBeAg positive with high levels of virus in the serum and minimal hepatic inflammation; phase 2 patients have intermittent or continuous hepatitis of varying degrees of severity; phase 3 is the inactive phase during which viral concentrations are low and there is minimal inflammatory activity in the liver. In general, patients who clear HBeAg have a better prognosis than patients who remain HBeAg-positive for prolonged periods of time. The outcome after anti-HBe seroconversion depends on the degree of pre-existing liver damage and any subsequent HBV reactivation. Without pre-existing cirrhosis, there may be only slight fibrosis or mild chronic hepatitis, but with pre-existing cirrhosis, further complications may ensue. HBsAg-negative chronic hepatitis B is a phase of chronic HBV infection during which a mutation arises resulting in the inability of the virus to produce HBeAg. Such patients tend to have more severe liver disease and run a more rapidly progressive course. The annual probability of developing cirrhosis varies from 0.1 to 1.0% depending on the duration of HBV replication, the severity of disease and the presence of concomitant infections or drugs. The annual incidence of hepatic decompensation in HBV-related cirrhosis varies from 2 to 10% and in these patients the 5-year survival rate drops dramatically to 14-35%. The annual risk of developing HCC in patients with cirrhosis varies between 1 and 6%; the overall reported annual detection rate of HCC in surveillance studies, which included individuals with chronic hepatitis B and cirrhosis, is 0.8-4.1%. Chronic hepatitis B is not a static disease and the natural history of the disease is affected by both viral and host factors. The prognosis is poor with decompensated cirrhosis and effective treatment options are limited. Prevention of HBV infection thorough vaccination is still, therefore, the best strategy for decreasing the incidence of hepatitis B-associated cirrhosis and HCC. PMID- 11197044 TI - Evaluation of miniature manometric techniques for the measurement of esophageal body pressure waves. AB - BACKGROUND AND AIMS: Perfused miniature manometric assemblies with lumina of 0.4 0.5 mm i.d. have been developed. Reduced luminal size offers the advantages of reduced assembly bulk and increased assembly complexity with greater numbers of lumina and lower manometric infusion volumes because of a slower perfusion rate. This study investigated the recording fidelity of miniature manometric assemblies in the measurement of esophageal peristalsis. METHODS: Four miniature manometric assemblies, each containing manometric lumina of either 0.4 or 0.5 mm i.d., were evaluated at 100 and 180 cm lengths. The fidelity of miniature manometric luminal recordings were evaluated in vivo during esophageal peristalsis by using a simultaneous comparison with the standard lumina and an intraluminal strain gauge. RESULTS: During esophageal peristalsis, miniature manometric lumina recorded the peak amplitude of pressure waves, with an accuracy at perfusion rates of 0.04 mL/min (0.4 mm, i.d.) and 0.15 mL/min (0.5 mm, i.d.). CONCLUSION: Miniature manometric assemblies of lengths that are practical for use in humans are suitable for recording esophageal peristalsis. PMID- 11197045 TI - Histological analysis of gastritis and Helicobacter pylori infection in patients with early gastric cancer: a case-control study. AB - BACKGROUND AND AIMS: Infection with Helicobacter pylori is associated with an increased risk of gastric adenocarcinoma. However, most patients with H. pylori infection will not develop gastric cancer. The aims of the present study were to examine which histological features, including H. pylori infection, would increase the risk of gastric cancer using a case-control study. METHODS: Three gastric biopsy specimens were taken from 72 patients with early gastric cancer and 72 age- and sex-matched control subjects. The grade of gastritis was examined according to the updated Sydney System. The presence of H. pylori infection was determined by serology and histology. Odds ratio (OR) of developing gastric cancer was calculated for H. pylori positivity and histological features using conditional logistic regression. For patients with H. pylori infection, histological features in cancer patients and control subjects were compared. RESULTS: The OR of the presence of mononuclear cell infiltration in the corpus and intestinal metaplasia in the angulus were significantly elevated. The grade of mononuclear cell infiltration in the corpus and antrum was significantly higher in both types of cancer patients than controls. Glandular atrophy and intestinal metaplasia were increased in patients with intestinal-type cancer in the angulus and antrum. Bacterial density in the corpus and polymorphonuclear cell infiltration in the antrum were increased in patients with diffuse-type cancer. CONCLUSIONS: Severe chronic gastritis induced by H. pylori infection seems to be associated with diffuse-type gastric cancer. Glandular atrophy and intestinal metaplasia, which occur in gastric mucosa with chronic inflammation, are significantly associated with intestinal-type cancer. PMID- 11197046 TI - A short-term eradication therapy for Helicobacter pylori acute gastritis. AB - BACKGROUND AND AIMS: Acute gastritis, caused by an initial infection of Helicobacter pylori (H. pylori), may resolve spontaneously, but the infection sometimes becomes chronic. We examined the efficacy of a short-term H. pylori eradication therapy on acute gastritis. METHODS: Among the 15 patients with hemorrhagic acute gastritis who were randomly allocated to group A (eradication therapy) or group B (Lansoprazole, LPZ), 10 of them started to receive treatment within 1 day after the disease onset. The other five patients began the eradication therapy 4-6 days after disease onset (group C). Eradication therapy consisted of a daily oral administration of each of 30 mg lansoprazole (LPZ), once a day; 400 mg clarithromycin, twice a day; 1000 mg amoxicillin, twice a day; and 300 mg rebamipide, three times a day, for one week. If the endoscopy was normal, medication was stopped for the following 4 weeks before gastric endoscopy was performed again in order to assess H. pylori eradication. RESULTS: All group A patients were cured after the 1-week treatment and therefore, they became H. pylori negative. Group B and C patients had erosions or ulcers after the 1-week treatment and so received an additional 3-week administration of LPZ. Four weeks later, their gastritis was cured and except for one group B patient, they became H. pylori-negative. CONCLUSION: In patients with acute gastritis, caused by an initial H. pylori infection, eradication therapy was efficacious in achieving early healing. This therapy should be started as soon as possible after disease onset. PMID- 11197047 TI - Helicobacter pylori infection among Japanese children. AB - BACKGROUND: In Japan, there are few reports describing Helicobacter pylori infection among young children. The aim of the present study was to identify risk factors associated with H. pylori in school-aged children. METHODS: Subjects were first-grade students of three elementary schools (n = 310) and second-grade students of a junior high school (n = 300). Personal information, such as student's medical history, parent's history, family size, sibshipsize and household pets, was collected from guardians using a questionnaire. Saliva samples and personal information were collected twice (1995 and 1996). By using the saliva samples, H. pylori IgG antibody was measured using a commercial kit. To analyze the risk factors for H. pylori infection, sex- and age-adjusted odds ratios (OR) were calculated using a multiple logistic model. RESULTS: Among the children, factors related to Helicobacter antibody in saliva included spending a longer period of time in a nursery school or kindergarten (OR = 4.0) and a maternal history of stomach disease (OR = 2.8). Birth order (OR = 2.2), sleeping situation (OR = 2.3) and sibshipsize (OR = 1.6) were not factors that were significantly related to Helicobacter antibody in the saliva. Chewing food for the infant, family size, rooms in the household, sharing a bedroom during childhood, pets, a past history and a paternal history were not related to positivity. CONCLUSIONS: The results indicate that transmission is person-to person, mainly through close contact with other children and intrafamilial infection. Helicobacter pylori infection seems to occur frequently early in life, probably before 6 years of age. PMID- 11197048 TI - Non-steroidal anti-inflammatory drugs with different cyclooxygenase inhibitory profiles that prevent aberrant crypt foci formation but vary in acute gastrotoxicity in a rat model. AB - BACKGROUND: Standard non-steroidal anti-inflammatory drugs (NSAIDs) reduce the risk of colorectal cancer; however, their use as preventive agents is limited by their inherent toxicity. Drugs that selectively inhibit cyclooxygenase-2 (COX-2) may be useful in this setting as they are supposedly less toxic. No study has directly compared the ability of standard NSAIDs and selective COX-2 inhibitors to inhibit colorectal cancer at clinically relevant doses. METHODS: Aberrant crypt foci (ACF) were induced in Sprague-Dawley rats by using 1,2 dimethylhydrazine (DMH). Test agents or vehicle were then administered for 3 weeks, twice daily through orogastric gavage. At the end of this period, the number and multiplicity of ACF were determined. The agents tested at equivalent anti-inflammatory doses were: sulindac and indomethacin (standard NSAIDs), meloxicam (selective COX-2 inhibitor), celecoxib (specific COX-2 inhibitor) and sulindac sulfone (no known COX activity). Acute gastrotoxicity of NSAID in rats was compared by using quantitative histology. RESULTS: All test agents reduced the number of ACF. There was a 42% reduction with indomethacin, 46% with sulindac, 46% with meloxicam, 22% with celecoxib and 36% with sulindac sulfone. Only the COX-2 inhibitors caused no significant gastrotoxicity in rats. CONCLUSIONS: Cyclooxygenase-2 inhibitors are potentially ideal chemopreventive agents as they inhibit ACF and are not gastrotoxic. PMID- 11197049 TI - Overexpression of c-H-ras p21 is correlated with vascular endothelial growth factor expression and neovascularization in advanced gastric carcinoma. AB - BACKGROUND AND AIMS: ras Gene and its product (p21) have been reported to be associated with vascular endothelial growth factor (VEGF), which is one of the most important angiogenic factors, and tumor-associated angiogenesis. We tried to evaluate the correlation between the expression of c-H-ras gene product p21 and angiogenesis in advanced gastric carcinoma. METHODS: Immunohistochemical expression of c-H-ras p21 and VEGF was examined in 49 advanced gastric adenocarcinomas. In addition, double immunohistochemical staining was performed using anti-CD34 and anti-Ki-67 antibodies, and the intratumoral microvessel densities and their endothelial proliferative labeling indices were then counted to evaluate the degree of angiogenesis. RESULTS: The expression of c-H-ras p21 was demonstrated in 43 out of 49 gastric adenocarcinomas (87.8%). It did not correlate with histologic type, depth of invasion or metastasis. However, the degree of c-H-ras p21 expression was correlated with VEGF. In addition, the degree of c-H-ras p21 expression was correlated with increased intratumoral microvascular density and endothelial proliferative activity. CONCLUSIONS: We suggest that c-H-ras oncogene product p21 contributes to the upregulation of tumor-associated angiogenesis by the increased production of VEGF in advanced gastric carcinomas. Therefore, treatment involving the targeting of ras oncogene could inhibit solid tumor growth by suppressing tumor-associated angiogenesis. PMID- 11197050 TI - Decreased anti-Saccharomyces cerevisiae antibody titer by mesalazine in patients with Crohn's disease. AB - BACKGROUND: Saccharomyces cerevisiae may contribute to the pathophysiology of Crohn's disease. We determined serum anti-Saccharomyces cerevisiae antibody (ASCA) levels in patients with inflammatory bowel disease. METHODS AND RESULTS: Immunoglobulin G (IgG) ASCA was measured by using an ELISA in serum samples from 19 patients with ulcerative colitis, 18 patients with Crohn's disease and 7 healthy controls. The ASCA level was significantly higher in patients with ulcerative colitis and patients with Crohn's disease than in controls, and was significantly higher in patients with Crohn's disease compared with patients with ulcerative colitis. Age, gender, disease activity, extent of disease and small bowel involvement each did not affect ASCA levels. The use of elemental or polymeric diet therapy for Crohn's disease and administration of corticosteroids to patients with inflammatory bowel disease also did not affect ASCA levels. The ASCA titer was significantly lower in patients with Crohn's disease taking mesalazine than in those not taking it, although, serum IgG levels did not differ between these two groups, which might imply a suppression of IgG production by mesalazine at the intestinal level. CONCLUSIONS: The finding of increased serum ASCA titers in patients with inflammatory bowel disease suggests that Saccharomyces cerevisiae may play a role in the pathophysiology of this condition. PMID- 11197051 TI - Status and natural course of GB virus C/hepatitis G virus infection among high risk groups and volunteer blood donors in Taiwan. AB - BACKGROUND: Hemophilia, thalassemia and uremia patients are at risk of parenterally transmitted infectious agents. The status and nature of the course of GB virus C/hepatitis G virus (GBV-C/HGV) infection among these groups and blood donors in Taiwan was investigated. METHODS: Serum GBV-C HGV-RNA and antibodies to GBV-C/HGV envelope-2-protein (anti-E2) were determined in 500 blood donors and in 44 hemophilia, 37 thalassemia and 85 uremia patients. Phylogenetic analysis was performed. RESULTS: The prevalence of GBV-C/HGV-RNA and anti-E2, respectively, was 38.6 and 27.3% in hemophilia patients, 27.0 and 27.3% in thalassemia patients, 14.1 and 10.6% in uremia patients and 3.4 and 7.2% in blood donors. The prevalence of GBV-C HGV exposure was 59.1 and 51.4% in hemophilia and thalassemia patients, respectively, which was significantly higher than that for uremia patients (22.4%; P < 0.01) and blood donors (10.2%; P < 0.001). The anti E2 seroconversion rate was 66.7% in blood donors and 47.4, 36.8 and 34.6% in thalassemia, uremia (P < 0.05 compared with blood donors) and hemophilia (P < 0.01 compared with blood donors) patients, respectively. Discrepancies in the prevalence of GBV-C HGV and hepatitis C virus infection were found among the three risk groups. Phylogenetic analysis showed that 51 of 56 GBV-C HGV isolates clustered in group 3; the remaining five were of group 2a. Twelve of 39 viremic patients in the risk groups cleared the virus during the 4 year follow-up period; seven developed concomitant anti-E2 reactivity. CONCLUSIONS: GB virus C hepatitis G virus infection is epidemic among risk groups and GBV-C HGV group 3 is the major strain in Taiwan. In the risk groups, approximately 18% of infections resolve with concomitant anti-E2 seroconversion within 4 years. PMID- 11197052 TI - Chronic hepatitis C is mild in menstruating women. AB - BACKGROUND AND AIMS: Women with chronic hepatitis C may have a slower rate of disease progression than men. We have previously demonstrated a relationship between hepatic iron concentration and liver fibrosis in patients with chronic hepatitis C. Our aim was to compare hepatic histologic findings, iron status and other factors putatively capable of determining the severity of chronic hepatitis between menstruating women and men of comparable age. METHODS: We studied 21 consecutive hepatitis C virus (HCV)-RNA positive menstruating women and 24 consecutive HCV-RNA positive men of comparable age, who underwent liver biopsy for chronic hepatitis C. Alcohol intake was recorded and blood tests, HCV genotyping, serum iron, unsaturated iron binding capacity, serum ferritin, hepatic iron concentration, and liver histology were evaluated. RESULTS: Menstruating women showed lower grading (2.7 +/- 1.5 vs 3.6 +/- 2, P = 0.09) and significantly lower staging (1.38 +/- 1.11 vs 2.42 +/- 1.64, P = 0.037) scores than men of comparable age. Among the factors putatively capable of determining the severity of chronic hepatitis, only the hepatic iron concentration correlated with the hepatic histologic staging in a multivariate analysis. Iron-depleted women (transferrin saturation < 20% and/or serum ferritin < 9 micrograms/L) showed significant lower hepatic histologic grading (1.75 +/- 0.7 vs 3.23 +/- 1.55, P = 0.027) and staging (0.75 +/- 1.03 vs 1.77 +/- 1.01, P = 0.026) scores than women with normal iron status. CONCLUSIONS: Menstruating women with chronic hepatitis C may have a milder disease compared to men of comparable age, possibly because of menstrual blood loss and lower hepatic iron concentration. Women with chronic hepatitis C and iron deficiency have a milder disease compared to women with normal iron status, suggesting that iron deficiency results in a slower rate of disease progression. PMID- 11197053 TI - Efficacy of consensus interferon in the treatment of chronic hepatitis C. AB - BACKGROUND AND AIMS: Consensus interferon (CIFN) is a newly developed type I interferon. The aim of this study was to investigate the safety and efficacy of CIFN in the treatment of patients with chronic hepatitis C and to determine the predictors for sustained response. METHODS: Patients were randomized to receive 3 micrograms or 9 micrograms CIFN three times a week for 24 weeks, followed by 24 weeks of observation. Efficacy was assessed by normalization of serum transaminase levels and disappearance of serum hepatitis C virus (HCV)-RNA at the end of treatment and at 24 weeks after stopping treatment. Histologic response was defined as a decrease of at least two points in the Knodell necroinflammatory score at week 48 and was compared with baseline. RESULTS: There were no serious adverse effects related to CIFN therapy. Overall, 44% of patients receiving 3 micrograms and 48% of patients receiving 9 micrograms had normalization of serum transaminase levels and disappearance of HCV viremia at the end of treatment. At 24 weeks after stopping treatment, 16% of patients in receiving 9 micrograms and 12% of patients receiving 3 micrograms had sustained responses. The histologic responses in patients receiving 9 micrograms and those receiving 3 micrograms were 60% and 36%, respectively. The necroinflammatory score was significantly reduced from baseline to week 48 in both groups. In addition, bodyweight < 60 kg and pretreatment serum HCV-RNA level < 0.5 MEq/mL can serve as predictors for sustained response to CIFN treatment. CONCLUSIONS: These findings suggest that 9 micrograms CIFN is safe and effective in the treatment of patients with chronic hepatitis C. PMID- 11197055 TI - Gastrointestinal: double pylorus. PMID- 11197054 TI - Renovascular resistance assessed by color Doppler ultrasonography in patients with chronic liver diseases. AB - BACKGROUND AND AIMS: Renal arterial vasoconstriction is known to be related to renal hemodynamic derangement in patients with liver cirrhosis. Using color Doppler ultrasonography in patients with chronic liver diseases, abnormal resistance in the renal artery was examined non-invasively both cross-sectionally and longitudinally to clarify the relationship between renal vascular resistance and liver function to neurohumoral factors. METHODS: The study comprised 118 patients with cirrhosis, 23 patients with chronic hepatitis, and 35 healthy controls. Pulsatility and resistive indices that were derived from renal artery velocity analysis were used as parameters of renal arterial resistance. RESULTS: Both the pulsatility and resistive indices were significantly higher in cirrhotic patients (1.29 +/- 0.37, P < 0.001 and 0.69 +/- 0.07, P < 0.001, respectively) compared to controls (1.00 +/- 0.12 and 0.62 +/- 0.05, respectively) and compared to patients with chronic hepatitis (0.97 +/- 0.13 and 0.60 +/- 0.05, respectively). Both indices showed significant correlation with increased Child Pugh grade. Each correlated significantly with plasma renin activity and plasma aldosterone and norepinephrine levels. Multivariate analysis of the relationship between neurohumoral factors and renal arterial resistance disclosed that plasma renin activity was a significant independent predictor. The longitudinal change in pulsatility index, resistive index and neurohumoral factors were examined in the cirrhotic patients who were followed-up for longer than 6 months. Pulsatility and resistive indices increased according to the deterioration of liver function and the changes in both indices were closely related to the change in plasma renin activity. CONCLUSIONS: Pulsatility index and resistive index as measured by color Doppler ultrasonography were closely related to the severity of cirrhosis and to the levels of neurohumoral factors, especially plasma renin activity, in this cross-sectional and longitudinal study. Therefore, they are useful indices for assessing renal hemodynamics in patients with cirrhosis. PMID- 11197056 TI - Hepatobiliary and pancreatic: small liver tumor. Small hepatocellular carcinoma with fatty changes. PMID- 11197057 TI - A balanced 5:1 carbohydrate:protein diet: a new method for supplementing protein to patients with chronic liver disease. AB - BACKGROUND AND AIMS: Protein malnutrition in patients with chronic liver disease contributes to bone and muscle weakness and compromises immune function and survival. In contrast, high-protein diets may induce or exacerbate hepatic encephalopathy. The aim of the present study was to test whether increased amounts of protein, balanced by dietary carbohydrate in a 1:5 ratio, may be given to chronic liver disease patients in order to minimize postprandial increases in plasma amino acid (AA) concentrations. METHODS: Eight patients with chronic liver disease were studied. Each received, in a randomized order, three different diets of 2510 kJ of either high protein (37:50:28, carbohydrate:protein:fat), high carbohydrate (126:10:6) or a balanced 5:1 carbohydrate:protein diet (105:21:11). All patients were followed for plasma AA, glucose and insulin levels, as well as for cognitive and behavioral changes. RESULTS: Following the high protein diet, AA concentrations were significantly increased. In contrast, after the balanced diet, AA levels were practically constant enabled. All diets was well tolerated and no cognitive or behavioral changes appeared. CONCLUSION: The administration of a balanced 5:1 carbohydrate:protein diet may enable patients with chronic liver disease to tolerate increased amounts of dietary protein, without altering plasma amino acid concentrations. PMID- 11197058 TI - Parathyroid hormone-related peptide producing cholangiocellular carcinoma with a marked psammoma formation. AB - Humoral hypercalcemia caused by parathyroid hormone-related peptide (PTHrP), associated with cholangiocellular carcinoma (CCC), has rarely been documented. There have been no reports of CCC associated with extensive calcification of the tumor with psammoma body formation. A 66-year-old man was admitted with a large calcified tumor in the liver detected on an abdominal X-ray. An ultrasound-guided fine needle biopsy specimen of the liver tumor showed evidence of adenocarcinoma. He had hypercalcemia with an elevated PTHrP level. The patient died because of disseminated intravascular coagulation and progressive hepatic failure. A postmortem examination revealed a large poorly differentiated CCC in the liver. Immunohistochemical examination showed the presence of PTHrP-positive tumor cells. The calcified lesion consisted of a number of accumulated psammoma bodies. We present a case of PTHrP producing CCC with a marked psammoma formation. PMID- 11197059 TI - Advanced hepatocellular carcinoma with distant metastases, successfully treated by a combination therapy of alpha-interferon and oral tegafur/uracil. AB - We report a case of advanced hepatocellular carcinoma (HCC), successfully treated by a combination therapy of alpha-interferon (IFN-alpha) and tegafur/uracil (UFT). A 44-year-old Japanese man who underwent a partial hepatectomy for HCC developed tumor recurrence in the liver 10 months after surgery. Transcatheter arterial chemoembolization (TAE) was performed twice within 7 months, but was ineffective. Later, multiple metastatic lesions appeared in the liver, lung and spine. Following the third TAE, a combination therapy of IFN-alpha (10 x 10(6) units, i.m., t.i.w.) and UFT (300 mg, p.o.d.) was started. The treatment resulted in a fall in serum PIVKA-II (protein induced by vitamin K antagonism) levels from 906 mAU to normal levels and a complete resolution of all lung nodules within 6 months. At the latest follow up 24 months after the initiation of combination treatment, the patient was working full-time and showed no evidence of tumor relapse. A combination therapy of IFN-alpha and UFT may be promising for the treatment of advanced HCC. PMID- 11197060 TI - A multimodal intervention for grandparents raising grandchildren: results of an exploratory study. AB - This article describes the results of an exploratory study of a multimodal, home based intervention designed to reduce psychological stress, improve physical and mental health, and strengthen the social support and resources of grandparents raising grandchildren. The six-month intervention included home visits by registered nurses, social workers, and legal assistants; the services of an attorney; and monthly support group meetings. The intervention resulted in improved mental health scores, decreased psychological distress scores, and increased social support scores. Participants also experienced improvement in the level of public benefits received and in their legal relationships with their grandchildren. Implications of these findings for practice are highlighted. PMID- 11197061 TI - Helping foster parents cope with separation, loss, and grief. AB - Major changes in planning for children in foster care have resulted in significant changes in the roles of and expectations for foster parents, accompanied by even less attention to the issues of foster families' grief and loss. This article focuses on (1) the many ways foster parents encounter loss and grief on a continuous basis; (2) factors that affect the intensity of the loss and the healthy expression and resolution of grief; (3) problems that can result when the grief of foster parents is not adequately addressed; and (4) ways in which professionals can be helpful to these caregivers around loss and grief. PMID- 11197062 TI - How soon is too soon? Addiction recovery and family reunification. AB - This article describes the addiction recovery process and its impact on parenting behaviors-information needed by child welfare workers involved in decisionmaking regarding family reunification. Two models of recovery-from alcoholism and from cocaine addiction-are reviewed, along with issues encountered in recovery, particularly for women. Case examples and discussion demonstrate how child welfare workers can apply these models in determining the appropriateness of reunification. PMID- 11197063 TI - The postadoption experience: child, parent, and family predictors of family adjustment to adoption. AB - Eighteen to 24 months after they adopted children in state custody, 159 parents were surveyed regarding their postadoption experiences. Most children remained with their new families, with parents reporting the adoption experience to be "about as hard as expected," and rating the past year of caring for the child as being more "smooth" than "stressful." Parents saw how the child contributed positively to their lives, were less positive about available social supports, and expressed dissatisfaction with the speed of the adoption, the availability of community supports, and the ability to link with supports. Children's special needs (e.g., older age at adoption) were predictive of postplacement adjustment. PMID- 11197064 TI - Effects of clofibrate and indocyanine green on the hepatobiliary disposition of acetaminophen and its metabolites in male CD-1 mice. AB - 1. The effects of clofibrate (CFB) and indocyanine green (ICG) on the biliary excretion of acetaminophen (APAP) and its metabolites were investigated. 2. Male CD-1 mice were pretreated with 500 mg CFB/kg, i.p. for 10 days. Controls received corn oil vehicle only. After overnight fasting, common bile duct-cannulated mice were challenged with a non-toxic dose of APAP (1 mmol/kg, i.v.). 3. CFB pretreatment did not affect bile flow rate, nor did it affect the cumulative biliary excretion of APAP and its conjugated metabolites. 4. Additional CFB or corn oil pretreated mice were given 30 mumol indocyanine green (ICG)/kg, i.v., immediately before APAP dosing. ICG is a non-metabolizable organic anion that is completely excreted into the bile through a canalicular transport process for organic anions. 5. ICG significantly decreased the bile flow rate and biliary concentration of APAP-glutathione, APAP-glucuronide and APAP-mercapturate within the first hour after dosing without affecting the biliary concentration of APAP. 6. The results indicate that CFB pretreatment does not affect the total amount of APAP and its metabolites excreted in bile. They also suggest that the biliary excretion of several conjugated metabolites of APAP share the same excretory pathway with the organic anion ICG. PMID- 11197065 TI - In vitro identification of the cytochrome P450 isoform responsible for the metabolism of alpha-dihydroergocryptine. AB - 1. The in vitro metabolism of alpha-dihydroergocryptine (DHEC, Almirid), an ergot derived dopamine agonist for the treatment of Parkinson's disease, has been studied in cultured cell lines following incubation with DHEC. Human hepatocytes as well as two sets of metabolically competent cell lines expressing one single human cytochrome P450 (1A1, 1A2, 1B1, 2A6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4) were used. 2. Mono- and dihydroxy metabolites of DHEC could only be detected in the culture media of the cell line expressing human cytochrome CYP3A4. The same metabolites were found in the media of cultured human hepatocytes derived from three different donors. After 24-h incubation with 1 microM DHEC, approximately 60% mono- and approximately 20% dihydroxy metabolites were detected, i.e. approximately 80% of DHEC was metabolized. Further, DHEC demonstrated an inhibitory effect on CYP3A4-mediated testosterone metabolism and additionally could induce CYP3A4 and CYP2E1 mRNA when added at 10 microM to cultured human hepatocytes. 3. The data suggest that DHEC metabolism in humans is primarily mediated by the CYP3A4 isoform. The results are in accordance with findings derived from other ergot alkaloids. PMID- 11197066 TI - Glucuronidation of resveratrol, a natural product present in grape and wine, in the human liver. AB - 1. Resveratrol, a polyphenolic compound present in grape and wine, has beneficial effects against cancer and protective effects on the cardiovascular system. It has been shown that the compound is sulphated in human liver and the aims of the present investigation were to study resveratrol glucuronidation in human liver microsomes and to determine whether flavonoids inhibit resveratrol glucuronidation. 2. A simple and reproducible radiometric assay for resveratrol glucuronidation was developed. The assay employed uridine-5'-diphosphoglucuronic acid-[14C] and unlabelled resveratrol. Resveratrol-glucuronide was isolated by TLC. The intra- and interassays variabilities were 1 and 1.5%, respectively. 3. The rate of resveratrol glucuronidation was measured in 10 liver samples. The mean +/- SD and median of resveratrol glucuronidation rate were 0.69 +/- 0.34 and 0.80 nmol/min/mg, respectively. Resveratrol glucuronosyl transferase followed Michaelis-Menten kinetics and the Km and Vmax (mean +/- SD; n = 5) were 0.15 +/- 0.09 mM and 1.3 +/- 0.3 nmol/min/mg, respectively. The intrinsic clearance was 11 +/- 4 x 10(-3) ml/min.mg. 4. The flavonoid quercetin inhibited resveratrol glucuronidation and its IC50 (mean +/- SD; n = 3) was 10 +/- 1 microM. Myricetin, catechin, kaempferol, fisetin and apigenin (all at 20 microM) inhibited resveratrol glucuronidation and the percent of control ranged between 46% (catechin) to 72% (apigenin). 5. The present results show that resveratrol is glucuronated in the human liver. Glucuronidation may reduce the bioavailability of this compound however, flavonoids inhibit resveratrol glucuronidation and such an inhibition might improve the bioavailability of resveratrol. PMID- 11197067 TI - Metabolism of 26,27-hexafluoro-1 alpha,25-dihydroxyvitamin D3 and 26,27 hexafluoro-1 alpha,23(S)25-trihydroxyvitamin D3 in ROS17/2.8 cells transfected with a plasmid expressing CYP24. AB - 1. To clarify the possibility that the metabolism of 26,27-hexafluoro-1 alpha,25 dihydroxyvitamin D3 [F6-1,25(OH)2D3] to 26,27-hexafluoro-1 alpha,23(S),25 trihydroxyvitamin D3 [F6-1,23,25(OH)3D3 and that of F6-1,23,25(OH)3D3 to 26,27 hexafluoro-23-oxo-1 alpha,25-dihydroxyvitamin D3 [F6-23-oxo-1,25(OH)2D3] are catalysed by 25-hydroxyvitamin D3 24-hydroxylase (CYP24), ROS17/2.8 cells transfected with a plasmid expressing CYP24 [pSVL-CYP24(+)] and a corresponding blank plasmid [pSLV-CYP24R(-)] were used. 2. Incubation of [1 beta-3H]-F6 1,25(OH)2D3 for 2 and 5 days with ROS17/2.8 cells transfected with pSVL-CYP24(+) generated a metabolite that co-migrated with authentic F6-1,23,25(OH)3D3 in both normal phase and reversed-phase HPLC systems. 3. Incubation of [1 beta-3H]-F6 1,23,25(OH)3D3 for 5 days with pSVL-CYP24(+)- transfected ROS 17/2.8 cells generated a metabolite that co-migrated with authentic F6-23-oxo-1,25(OH)2D3. In contrast, the metabolites F6-1,23,25(OH)3D3 or F6-23-oxo-1,25(OH)2D3 were not generated in the cells transfected with pSVL-CYP24R(-). 4. The results indicate that CYP24 catalyses the conversion of F6-1,25(OH)2D3 to F6-1,23,25(OH)3D3 and that of F6-1,23,25(OH)3D3 to F6-23-oxo-1,25(OH)2D3. PMID- 11197068 TI - Isolation and cultivation of Ca2+ tolerant cardiomyocytes from the adult rat: improvements and applications. AB - 1. Primary cultures of cardiomyocytes provide a valuable tool for the study of the pharmacological and toxicological properties of drugs and chemicals, but for several technical reasons cardiomyocytes from adult animals are not routinely used in long-term culture. Because of significant advances in cardiovascular research, tissue engineering and cell transplantation, the need to isolate primary cells from adult animal and/or human tissue is likely to increase in the future. 2. The most common protocols for the isolation and cultivation of cardiomyocytes have been reviewed and the various approaches have been compared. The recent advances in cell culture techniques and the use of the cytoprotective agent, e.g. 2,3-butanedione monoxime greatly increases cell yield and cell viability of isolated and cultured cardiomyocytes. New concepts emerge that enabled an assessment of cellular differentiation in cultured cardiomyocytes and certain specific nuclear transcription factors may play a pivotal role in this process. PMID- 11197069 TI - Skeletal muscle kinetics of propofol in anaesthetized sheep: effect of altered muscle blood flow. AB - 1. The kinetics of propofol were studied in vivo in a skeletal muscle bed of the hindlimb of the anaesthetized sheep at normal and low rates of blood flow. 2. Propofol kinetics in muscle were determined during and after a 20-min i.v. infusion of propofol (10 mg min-1) via paired arteriofemoral venous blood sampling. One-and-a-half hours later, the study was repeated but with a concurrent left femoral artery infusion of adrenaline (0.004 mg min-1) to lower the muscle blood flow by vasoconstriction. 3. Muscle blood flow in the low flow state was 28% of that in the normal state. The kinetics were poorly described by a single flow-limited compartment model, but were better described by a model with a flow-limited component and a deeper distribution component. There were no significant differences in muscle retention of propofol between normal and low flow states. 4. There was an apparent arteriovenous shunt of approximately 24% of total muscle blood flow for the low flow state, but not for the normal blood flow state. PMID- 11197070 TI - Mass spectrometric and NMR characterization of metabolites of roxifiban, a potent and selective antagonist of the platelet glycoprotein IIb/IIIa receptor. AB - 1. The methyl ester prodrug roxifiban is an orally active, potent and selective antagonist of the platelet glycoprotein GPIIb/IIIa receptor and is being developed for the prevention and treatment of arterial thrombosis. 2. Roxifiban was rapidly hydrolyzed to the zwitterion XV459 in vivo and by liver slices from the rat, mouse and human and by intestinal cores from dog. XV459 was metabolized to only a small extent in vitro and in vivo. 3. Studies with rat and dog given radiolabelled roxifiban showed limited oral absorption with the majority of the radiolabel being excreted in faeces. After i.v. doses of 14C-roxifiban, most of the radioactivity was recovered in the urine of rat whereas the dog excreted significant amounts of radioactivity in bile and urine. 4. XV459 could be metabolized extrahepatically by dog gut flora to produce an isoxazoline ring opened metabolite. In vitro hepatic metabolism of XV459 was mainly by hydroxylation at the prochiral and chiral centres of the isoxazoline ring. These hydroxylated metabolites were not detected in the urine and plasma of human volunteers administered roxifiban. 5. Initial LC/MS identification of metabolites was achieved by dosing the rat with an equimolar mixture of d0:d4 roxifiban and detecting isotopic clusters of pseudomolecular ions. Unequivocal characterization of these metabolites was achieved by LC/MS, LC/NMR and high-field NMR techniques using synthetic standards of the metabolites. 6. The synthesis of one hydroxylated metabolite enabled the assignment of the correct stereochemistry of the substituted hydroxyl group on the isoxazoline ring. PMID- 11197071 TI - Transdermal delivery of the potent analgesic dihydroetorphine: kinetic analysis of skin permeation and analgesic effect in the hairless rat. AB - Dihydroetorphine is an extraordinarily strong opioid analgesic. To assess its effectiveness after topical application in hairless rats we have examined the kinetic analysis of skin permeation through excised skin and the in-vitro reservoir effect of skin, and have investigated the predictability of plasma concentration and analgesic effect following in-vivo transdermal application. Dihydroetorphine was moderately permeable from an aqueous suspension through excised hairless rat skin. Dihydroetorphine flux from drug-dispersed pressure sensitive adhesive tape was threefold that from the applied aqueous suspension. The fluxes through the abdominal and the dorsal skin during tape application fitted the Fickian diffusion equation well after the tape was removed peeling off the outer layer of the stratum corneum. The relationship between the plasma concentration and the analgesic effect was examined for four different rates of infusion of dihydroetorphine. A non-linear pharmacokinetic disposition was observed. Following abdominal (0.28 cm2, 20 microg) and dorsal (0.50 cm2, 35 microg) applications of the dihydroetorphine tape, plasma concentration (0.2-0.8 ng mL(-1)) and analgesic effect were maintained at a suitable level, for more than 8 h, until removal of the tape. These profiles were predictable using the combined equation for percutaneous absorption, disposition and the analgesic effect, but the analgesic effect was slightly lower than the predicted value. The results show that it was possible to control the plasma concentration and the analgesic effect of dihydroetorphine by topical application of the analgesic using pressure-sensitive adhesive tape in the hairless rat. It was possible to predict the result using mathematical modelling. PMID- 11197072 TI - Sustained release of 5-fluorouracil from polymeric nanoparticles. AB - The use of biodegradable nanoparticles loaded with 5-fluorouracil was investigated as a potential means to sustain the release of this drug. Nanoparticles prepared from four biodegradable polymers were loaded with 5 fluorouracil using three loading concentrations of drug and three different concentrations of added polymer. Washing particles using a centrifugation/re suspension with ultrasound protocol was found to dislodge the majority of drug, resulting in an over-estimation of incorporation efficiency and low levels of strongly entrapped drug. Increasing the initial 5-fluorouracil concentration before polymer/monomer addition increased the drug loading in both washed and unwashed particles. Increasing the amount of polymer used to make nanoparticles did not increase loadings, but did produce increased amounts of unusable polymer waste. Drug release from nanoparticles was evaluated using a Franz cell diffusion apparatus, which showed an initial burst effect followed by a slower release phase over 24 h. Indeed, nanoparticles prepared from poly(lactide-co-glycolide) released 66% of their 5-fluorouracil payload over this period. It was concluded that 5-fluorouracil-loaded nanoparticles could be readily included into a hydrogel-based delivery system to provide sustained drug release for trans epithelial drug-delivery applications. PMID- 11197073 TI - Enhancement of anti-metastatic activity of pentoxifylline by encapsulation in conventional liposomes and sterically stabilized liposomes in murine experimental B16F10 melanoma model. AB - Pentoxifylline has been shown to exhibit anti-metastatic activity by inhibiting homing of B16F10 melanoma cells in the murine experimental metastasis model. In this study, the effect of encapsulation of pentoxifylline in conventional and sterically stabilized liposomes on its anti-metastatic activity in the murine experimental metastasis model was investigated. After a single intravenous dose (10, 20 or 40 mg kg(-1)), pentoxifylline solution, as well as conventional pentoxifylline liposomes, significantly reduced the number of pulmonary nodules compared with the untreated control group. Conventional pentoxifylline liposomes showed significantly higher inhibition (69%) of pulmonary tumour nodule formation at a dose of 20mg kg(-1) as compared with pentoxifylline solution (49%) at the same dose. Encapsulation of pentoxifylline in sterically stabilized liposomes prepared by incorporation of monomethoxypolyethyleneglycol (5000)-cholesteryl ester further enhanced the inhibition of pulmonary nodule formation (77%) at a dose of 20 mg kg(-1) as compared with conventional pentoxifylline liposomes. Overall, the results suggest that encapsulation of pentoxifylline in conventional liposomes enhanced its anti-metastatic activity. Steric stabilization of pentoxifylline liposomes also resulted in a two-fold increase in anti-metastatic activity (at dose of 10 mg kg(-1)) as compared with conventional liposomes. PMID- 11197074 TI - Pharmacokinetics and bioavailability of tacrolimus in rats with experimental renal dysfunction. AB - The effects of renal failure on the pharmacokinetics and bioavailability of tacrolimus were investigated in rats. Experimental renal dysfunction was induced by intraperitoneal injection of cisplatin (5 mg kg(-1)) into rats. The blood concentration of tacrolimus was measured after intravenous and intra-intestinal administration of the drug. The blood concentration of tacrolimus after intravenous administration (1 mg kg(-1)) was slightly increased (up to 1.3 fold) by induction of renal dysfunction. In contrast, the peak tacrolimus concentration after intra-intestinal administration (1 mg kg(-1) or 3 mg kg(-1)) in rats with renal failure was about 2-fold higher than that in normal controls. The bioavailability was increased by about 35% in rats with impaired renal function as compared with normal controls. These results suggested that the bioavailability of tacrolimus, which is mainly metabolized in the liver and intestine after oral administration, is also influenced by renal function. PMID- 11197075 TI - Different effects of amitriptyline and imipramine on the pharmacokinetics and metabolism of perazine in rats. AB - The aim of this study was to search for possible effects of imipramine and amitriptyline on the pharmacokinetics and metabolism of perazine at steady state in rats. Perazine (10 mg kg(-1), i.p.) was administered to rats twice daily for two weeks, alone or jointly with imipramine or amitriptyline (10 mg kg(-1) i.p.). Concentrations of perazine and its two main metabolites (5-sulphoxide and N desmethylperazine) in the plasma and brain were measured at 30 min (Cmax), 6h and 12h (slow disposition phase) after the last dose of the drugs. Liver microsomes were prepared 24 h after withdrawal of the drugs. Amitriptyline increased the plasma and brain concentrations of perazine (up to 300% of the control) and N desmethylperazine, while not affecting those of 5-sulphoxide. Imipramine only tended to increase the neuroleptic concentration in the plasma and brain. Studies with control liver microsomes showed that amitriptyline and imipramine added to the incubation mixture in-vitro, competitively inhibited N-demethylation (Ki (inhibition constant) = 16 microM and 164 microM, respectively) and 5 sulphoxidation (Ki = 57 microM and 86 microM, respectively) of perazine, amitriptyline being a more potent inhibitor of perazine metabolism, especially with respect to N-demethylation. Studies with microsomes of rats treated chronically with perazine or tricyclic antidepressants, or both, did not show significant differences in the rate of perazine metabolism between perazine- and perazine+antidepressant-treated rats. The data obtained were compared with the results of analogous experiments with promazine and thioridazine. It was concluded that elevations of perazine concentration were caused by direct inhibition of the neuroleptic metabolism by the antidepressants. Similar interactions, possibly leading to exacerbation of the pharmacological action of perazine, may be expected in man. Since the interactions between phenothiazines and tricyclic antidepressants may proceed in two directions, reduced doses of both the neuroleptic and the antidepressant are recommended when the drugs are administered jointly. PMID- 11197076 TI - Effect of buthionine sulphoximine, glutathione and methimazole on the renal disposition of cisplatin and on cisplatin-induced nephrotoxicity in rats: pharmacokinetic-toxicodynamic analysis. AB - The aim of this study was to classify the protective mechanisms of DL-buthionine (S,-R)-sulphoximine, glutathione and methimazole on cisplatin-induced nephrotoxicity in rats. An Emax model was used to study the effect of these compounds on the pharmacokinetics of cisplatin, especially renal handling and intra-renal biotransformation. Cisplatin (5 mg kg(-1)) was administered as an intravenous bolus to rats treated with either 0.9% NaCl (control), buthionine sulphoximine, glutathione or methimazole. The blood urea nitrogen level was monitored to estimate cisplatin-induced nephrotoxicity. To estimate renal handling of cisplatin, cisplatin was infused intravenously to rats treated with 0.9% NaCl, buthionine sulphoximine, glutathione or methimazole. The concentrations of unchanged cisplatin in plasma, urine and kidney were determined by a post-column derivatization HPLC method. The relationship between the pharmacokinetics and toxicodynamics of cisplatin was analysed using a sigmoid Emax model. All compounds studied ameliorated significantly the nephrotoxicity of cisplatin. The renal accumulation of cisplatin was reduced significantly by pretreatment with buthionine sulphoximine but not by either glutathione or methimazole. Although glutathione treatment did not affect the renal accumulation of cisplatin, it significantly decreased the binding of cisplatin to the intrarenal organelle and the decreased binding was well correlated to the decrease of the blood urea nitrogen level. In summary, pharmacokinetic toxicodynamic analysis will be useful for classifying the protective mechanism of cisplatin-induced nephrotoxicity. PMID- 11197077 TI - Determination of tissue spaces of the isolated hindlimb of the rat using netilmicin as an extracellular space indicator. AB - The kinetic behaviour of drugs in extracellular space is of interest as it influences the drug's access to, and permanence in, those areas of the body upon which drugs exert pharmacological or toxicological actions. A series of experiments was carried out to characterize the vascular, interstitial and cellular spaces of the isolated hindlimb of the rat. Certain specific experimental conditions were met: body weight was under 230 g to avoid fat tissue in the preparations; a perfusion flow rate of 3 mL min(-1); and 3% of bovine albumin in the perfusate supplied at 25 degrees C to the tissues. The isolation of the hindlimb followed the method described by Ruderman with some modifications to restrict the perfusion to the right hindlimb. Tritiated water, netilmicin and methylene blue were injected separately and efferent fluid samples were collected for 15 min after solute injection. Analysis of the efferent curves was performed to calculate the statistical moments (AUC, area under concentration-time curve; MTT, mean transit time; VTT, variance of mean transit times) and solute distribution volumes, which were subsequently used to estimate the tissue spaces of the isolated hindlimb. The results revealed that methyl blue and netilmicin can be respectively used as alternatives to radiolabelled indicators of the vascular and extracellular spaces of tissues included in the rat isolated hindlimb. PMID- 11197078 TI - Time-dependent nephrotoxicity associated with daily administration of cisplatin in mice. AB - The chronopharmacokinetics and chronopharmacodynamics of cisplatin were studied in a mouse model to reveal the mechanisms of dosing time-dependent nephrotoxicity induced by daily administration. Chronotoxicity was tested by daily intraperitoneal injections of cisplatin (6mg kg(-1)) for 5 days at four time points (04:00, 10:00, 16:00 and 22:00h) in BALB/c mice (n = 6 in each group). After following the changes in body weight, serum concentrations of blood urea nitrogen (BUN) and creatinine obtained on day 6 were compared. The results showed diurnal variations in cisplatin toxicity, with the 04:00 and 16:00h time points the best and the worst, respectively. We then measured platinum concentrations in blood, liver and kidney and compared the results of the 04:00 and 16:00 h groups (n = 4 in each group). Kidney sensitivity to cisplatin alone, lipopolysaccharide (LPS) alone, cisplatin with LPS and saline (control) were also measured using a tissue culture system (a measurement system of interleukin-6 (IL-6) production) between the 04:00 and the 16:00 h groups (n = 4 in each group). These results showed no significant difference in platinum accumulation between the two groups. IL-6 production was higher in the 16:00 h group than in the 04:00 h group after saline injection alone (P < 0.05). Cisplatin treatment alone did not increase IL 6 production. However, IL-6 levels were markedly augmented by cisplatin with LPS. In conclusion, chrononephrotoxicity induced by daily cisplatin administration does not only depend on cisplatin accumulation, but might also depend on kidney sensitivity to diurnal variations in inflammatory reaction without direct cisplatin toxicity. PMID- 11197079 TI - Dammarane derivatives protect cultured rat cortical cells from glutamate-induced neurotoxicity. AB - We previously reported that ginsenosides Rb1 and Rg3, dammarane glycosides, of Panax ginseng C. A. Meyer (Araliaceae), significantly attenuated glutamate induced neurotoxicity in primary cultures of rat cortical cells. To seek more potent neuroprotective compounds, we attempted to modify the chemical structure of dammarane glycosides and obtained six derivatives, MA-11, PT-11, PT-111, POA 101, POA-111 and N-001. The neuroprotective activity of these dammarane derivatives were evaluated employing primary cultures of rat corticoid cells. The glutamate-induced neuronal cell damage was significantly reduced by a pre treatment with protopanaxadiol, MA-11 or PT-11 at concentrations ranging from 100 nM to 10 microM. Both MA-11 and PT-11, preserved the levels of catalase and inhibited decreases in glutathione reductase in glutamate-injured cells. Furthermore, the dammarane derivatives reduced the content of intracellular peroxide in glutamate-intoxicated cells. Finally, they inhibited the formation of malondialdehyde, a compound produced during lipid peroxidation, in glutamate insulted cells. These results show that the dammarane derivatives, MA-11 and PT 11, exert significant neuroprotective effects on cultured cortical cells by a mechanism seemingly distinct from that afforded by ginsenosides Rb1 and Rg3. As such, the dammarane derivatives may be efficacious in protecting neurons from oxidative damage caused by exposure to excess glutamate. PMID- 11197080 TI - Effects of Ba2+ on F&F 96365-sensitive sustained contraction of rat pulmonary artery. AB - The effects of Ba2+ on receptor-mediated sustained contraction of rat pulmonary artery and guinea-pig oesophageal muscularis mucosae were studied in-vitro. In rat isolated pulmonary artery, sustained contraction induced by noradrenaline (1 microM) was resistant to nicardipine (1 microM), but this same sustained contraction was completely inhibited by SK&F 96365 (30 microM), a blocker of voltage-dependent L-type Ca2+ channels and receptor-activated Ca2+ influx. The SK&F 96365-sensitive sustained contraction induced by noradrenaline (1 microM) may be due primarily to Ca2+ influx through receptor-activated Ca)+ channels resistant to nicardipine. Cumulatively applied BaCl2 (0.1 - 10 mM) increased the noradrenaline (1 microM)-induced sustained contraction of the pulmonary arterial preparation in the absence of nicardipine, but in the presence of nicardipine (1 microM), BaCl2 (0.1 - 3 mM) did not affect this contraction. A higher concentration of BaCl22 (10 mM), however, weakly inhibited the noradrenaline (1 microM)-induced tone. In addition, BaCl2 (3-10 mM) increased the tone induced by KCl (60 mM), and the BaCl2-elevated KCl tone was markedly inhibited by nicardipine (1 microM) treatment. In the guinea-pig isolated oesophageal muscularis mucosae, sustained contraction induced by acetylcholine (3 microM) was resistant to nicardipine (1 microM) but was returned to its basal level by SK&F 96365 (30-60 microM). The SK&F 96365-sensitive, acetylcholine-induced sustained contraction of the oesophageal muscularis mucosae is also likely to link with receptor-activated Ca2+ channels resistant to nicardipine. In contrast to the rat pulmonary artery, cumulatively applied BaC12 (0.3 - 10 mM) inhibited the acetylcholine (3 microM)-induced sustained contraction of the oesophageal muscularis mucosae in a concentration-dependent manner in the presence of nicardipine (1 microM). In conclusion, Ba2+ presumably activates voltage dependent Ca2+ channels by depolarizing plasma membrane and also passes through voltage-dependent Ca2+ channels to contract the pulmonary artery in the absence of nicardipine, and Ba2+ also has a minor effect on the nicardipine-resistant, SK&F 96365-sensitive sustained contraction induced by noradrenaline in rat isolated pulmonary artery. PMID- 11197081 TI - Effect of dimethylglycine on gastric ulcers in rats. AB - Dimethylglycine is an anti-stress nutrient with antioxidant properties. Recently, studies have implicated the generation of oxygen-derived free radicals and lipid peroxidation as one of the mechanisms in the pathogenesis of gastric ulcer. Hence, we evaluated the antiulcer activity of dimethylglycine in various rat models of ulcer and also investigated the probable antioxidant mechanism of the anti-ulcer effect. Dimethylglycine at a dose of 25 and 35 mg kg(-1) significantly reduced ulcer number, ulcer size and ulcer index in pyloric-ligation-, ibuprofen- and stress-induced ulcers. The 35 mg kg(-1) dose was more effective than 25 mg kg(-1) and was comparable to famotidine. Dimethylglycine did not produce any significant change in acid secretion, unlike famotidine. There was a significant increase in plasma and tissue malondialdehyde levels in pyloric-ligated rats but these levels fell following dimethylglycine treatment. Also, there was a significant reduction in glutathione levels after dimethylglycine treatment. The results suggest that the gastroprotective effect of dimethylglycine could be mediated by its free radical scavenging activity and cytoprotection of gastric mucosa. PMID- 11197082 TI - Clonidine attenuates the carbachol-induced contractile and phosphatidylinositol responses of rat trachea. AB - Although clonidine is known to affect vascular smooth muscle, its effects on airway smooth muscle are not fully understood. This study was designed to examine the effects of clonidine on carbachol-induced contractile and phosphatidylinositol responses of rat trachea. Clonidine, at a dose of 100 microM or greater, attenuated carbachol-induced contraction and the accumulation of carbachol-induced inositol monophosphate (IP1). Clonidine also attenuated the accumulation of aluminium fluoride-induced IP1. The concentration-effect relationship of IP1 accumulation was similar to that of carbachol-induced contraction; r = 0.797, P < 0.001. These results suggest that clonidine attenuates contractile responses, at least in part, through the inhibition of phospholipase C (coupled with G-proteins) in phosphatidylinositol responses. PMID- 11197083 TI - AL-3138 antagonizes FP prostanoid receptor-mediated inositol phosphates generation: comparison with some purported FP antagonists. AB - The aim of this study was to pharmacologically characterize the antagonist properties of a novel prostaglandin F2alpha (PGF2alpha) analogue (11-deoxy-16 fluoro PGF2alpha; AL-3138) using a variety of second-messenger assays of prostaglandin receptor subtypes. A detailed comparison was made between AL-3138 and some purported FP receptor antagonists such as PGF2alpha dimethylamine, PGF2alpha dimethylamide, glibenclamide and phloretin using the FP receptor mediated phosphoinositide turnover assay in A7r5 rat thoracic aorta smooth muscle cells and mouse Swiss 3T3 fibroblasts. The potency and efficacy of AL-3138 as an FP receptor agonist were: EC50 = 72.2 +/- 17.9 nM (Emax = 37%) (n = 3) in A7r5 cells and EC50 = 20.5 +/- 2.8 nM (Emax = 33%) (n = 5) in 3T3 cells. Being a partial agonist, the antagonist potency of AL-3138 against fluprostenol in A7r5 cells was determined to be: Ki = 296 +/- 17 nM (n = 3) and Kb = 182 +/- 44 nM (n = 5) (-log Kb = 6.79 +/- 0.1). AL-3138 exhibited very minimal or no antagonistic effects at EP2, EP4, DP and TP prostaglandin receptors. Both PGF2alpha dimethylamide and PGF2alpha dimethylamine were inactive as FP receptor antagonists, whereas phloretin and glibenclamide were very weak and had -log Kb values of 5.28 +/- 0.09 (n = 3) and 3.58 +/- 0.32 (n = 3), respectively. However, phloretin antagonized functional responses of EP2 and DP prostanoid receptors, and also the V1-vasopressin receptor. AL-3138 competed for [3H]PGF2alpha binding to FP receptors with a relatively high affinity (IC50high = 312 +/- 95 nM) matching its functional antagonist potency. In conclusion, AL-3138 is a more potent and selective FP receptor antagonist than glibenclamide, phloretin, PGF2alpha dimethylamide and PGF2alpha dimethylamine and is therefore a unique and novel pharmacological tool to help characterize FP receptor-mediated functions. PMID- 11197085 TI - Electron-microscopic study of the bactericidal effect of OPB-2045, a new disinfectant produced from biguanide group compounds, against methicillin resistant Staphylococcus aureus. AB - The bactericidal effect of OPB-2045, a new disinfectant produced from biguanide group compounds, against methicillin-resistant Staphylococcus aureus (MRSA), MRSA IID 1677, was investigated by transmission electron microscopy. OPB-2045 showed strong bactericidal activity against MRSA. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of OPB-2045 against the test strain were 0.78 and 1.56 microg mL(-1), respectively. The test bacteria were incubated in the presence of OPB-2045 at 1/2 MIC (0.39 microg mL(-1)), 1 MIC (0.78 microg mL(-1)), 2 MIC (1 MBC, 1.56 microg mL(-1)), 4 MIC (2 MBC, 3.13 microg mL(-1)) or 10 MIC (5 MBC, 7.8 microg mL(-1)) at 37 degrees C for 30 s, 3 min, 30 min or 6h. The morphology of the cells was examined by transmission electron microscopy. The cell damage observed after 30-min or 6-h incubation in the presence of OPB-2045 at 1/2 or 1 MIC was the same as that at 2, 4 or 10 MIC. The numbers of damaged MRSA cells increased according to the increase in concentration of added disinfectant, and the image of bacteriolysis was observed, too. After treatment at 1/2 or 1 MIC, a few leaking cells were recognized, but no destroyed cells were found. No morphological changes were observed after treatment at 1 or 2 MIC for 30 s, 3 min or 30 min. When the incubation time was extended to 6 h, morphological changes in the MRSA cells treated at 1 or 2 MIC were observed. When examining the relationship between the numbers of surviving bacteria and the MIC (MBC) values in soybean casein digest broth, no decrease in MRSA cell numbers was recognized in the untreated control or at 1/2 MIC, but a marked decrease in MRSA cell numbers was recognized as the OPB-2045 concentration was increased. The new disinfectant OPB-2045 would make a useful contribution to the medical field for the prevention of infections caused by pathogenic bacteria such as MRSA. PMID- 11197084 TI - Recombinant human lactoferrin is effective in the treatment of Helicobacter felis infected mice. AB - Recombinant human lactoferrin possesses in-vitro antibiotic and anti-inflammatory activity similar to the native form. It was tested for in-vivo activity in mice infected with the gastritis-inducing bacterium Helicobacter felis. A two-week course of treatment with lactoferrin was sufficient to partially reverse both infection-induced gastritis and the infection rate, and fully reverse gastric surface hydrophobicity changes. A comparison of lactoferrin with amoxicillin and standard triple therapy revealed no differences in infection rate. These results show that recombinant human lactoferrin is effective in a mouse model of Helicobacter infection, and support further testing of this promising agent for this application. PMID- 11197086 TI - Effects of Uncaria tomentosa total alkaloid and its components on experimental amnesia in mice: elucidation using the passive avoidance test. AB - The effects of Uncaria tomentosa total alkaloid and its oxindole alkaloid components, uncarine E, uncarine C, mitraphylline, rhynchophylline and isorhynchophylline, on the impairment of retention performance caused by amnesic drugs were investigated using a step-down-type passive avoidance test in mice. In this test, the retention performance of animals treated with the amnesic and test drugs before training was assessed 24 h after training. Uncaria tomentosa total alkaloid (10-20 mg kg(-1), i.p.) and the alkaloid components (10-40 mg kg(-1), i.p.), as well as the muscarinic receptor agonist oxotremorine (0.01 mg kg(-1), i.p.), significantly attenuated the deficit in retention performance induced by the muscarinic receptor antagonist scopolamine (3 mg kg(-1), i.p.). The effective doses of uncarine C and mitraphylline were larger than those of other alkaloid components. Uncarine E (20 mg kg(-1), i.p.) also blocked the impairment of passive avoidance performance caused by the nicotinic receptor antagonist mecamylamine (15 mg kg(-1), i.p.) and the N-methyl-D-aspartate (NMDA) receptor antagonist (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 7.5 mg kg(-1), i.p.), but it failed to affect the deficit caused by the benzodiazepine receptor agonist diazepam (2 mg kg(-1), i.p.). Rhynchophylline significantly reduced the mecamylamine-induced deficit in passive avoidance behaviour, but it failed to attenuate the effects of CPP and diazepam. These results suggest that Uncaria tomentosa total alkaloids exert a beneficial effect on memory impairment induced by the dysfunction of cholinergic systems in the brain and that the effect of the total alkaloids is partly attributed to the oxindole alkaloids tested. Moreover, these findings raised the possibility that the glutamatergic systems are implicated in the anti-amnesic effect of uncarine E. PMID- 11197087 TI - Baicalin, the predominant flavone glucuronide of scutellariae radix, is absorbed from the rat gastrointestinal tract as the aglycone and restored to its original form. AB - When baicalin was orally administered to conventional rats, it was detected in their plasma for 24 h after administration, but baicalein, the aglycone of baicalin, was not detected. However, when baicalin was given to germ-free rats, only a small amount of baicalin was detected in their plasma within 2 h after the administration, its AUC0-lim (the area under the concentration-time curve from 0 to last determination time) being 12.0% of that in conventional rats. Subsequently, a considerable amount (55.1 +/- 6.2%) of baicalin was recovered from the gastrointestinal tract even 4 h after administration. When baicalein was orally administered to conventional rats, however, baicalin appeared rapidly in their plasma at an AUC0-lim value similar to that obtained after oral administration of baicalin, despite the absence of baicalein in plasma. When intestinal absorption was evaluated by the rat jejunal loop method, baicalein was absorbed readily, but only traces of baicalin were absorbed. Moreover, in conventional rats a small amount (13.4 +/- 3.1%) of baicalin and an appreciable amount (21.9 +/- 3.4%) of baicalein were recovered from the gastrointestinal tract even 4 h after oral administration of baicalin, but only a small amount (3.93 +/- 1.43%) of baicalein was detected in the intestinal tract 1 h after administration of baicalein. Baicalin was transformed to baicalein readily by the rat gastric and caecal contents. When baicalin was administered orally to conventional rats, an appreciable amount of baicalein was recovered in their gastrointestinal tracts. Moreover, baicalein was efficiently conjugated to baicalin in rat intestinal and hepatic microsomes. These results indicate that baicalin itself is poorly absorbed from the rat gut, but is hydrolysed to baicalein by intestinal bacteria and then restored to its original form from the absorbed baicalein in the body. PMID- 11197088 TI - Obesity-related hospitalization costs to the U.S. Navy, 1993 to 1998. AB - The objective of this work was to estimate the cost to the U.S. Navy for obesity related hospital admissions by examining (1) inpatient utilization associated with obesity; (2) the rank order, probability, and total facility costs of obesity-related diagnosis-related groups (DRGs); and (3) expected inpatient expenses. The frequency and probability of inpatient events in the Navy's active duty population were derived from the Department of Defense's Retrospective Case Mix Analysis System. Medicare-based facility costs per DRG were estimated. These measures were combined in a decision-analytic model. Expected facility costs per obesity-related admission for active duty Navy personnel increased by age group from $3,328 for 18 to 24 year olds to $5,746 for 45 to 64 year olds. The annual avoidable inpatient cost for the Navy was estimated to be $5,842,627 for the top 10 obesity-related DRGs. Improvements to the Navy Physical Readiness Program and other interventions that may reduce obesity, obesity-related health care use, and the public economic burden should be pursued. PMID- 11197089 TI - The cost-saving potential of prevaccination antibody tests when implementing a mass immunization program. AB - A seroprevalence study of hepatitis A virus (HAV), hepatitis B virus (HBV), and varicella-zoster virus (VZV) was carried out among Saudi Arabian National Guard soldiers with the objective of determining the cost-saving potential of prevaccination antibody tests when implementing an immunization program for the soldiers. A systematic sampling of 450 blood samples from 1,350 soldiers who donated blood at our hospital was carried out. Antibody tests were performed using the enzyme-linked immunosorbent assay method. The seropositivity rates for antibodies to HAV, HBV, and VZV were 97.5, 17.8, and 88.5%, respectively. Comparing the cost of prevaccine screening with that of universal vaccination, it was estimated that savings of 76 and 32% could be effected for HAV and VZV. Conversely, screening for HBV before immunization could increase the cost of vaccinating against the disease by 49%. A seroprevalence study could be a useful cost-saving approach to a mass immunization program against endemic, natural immunity-conferring diseases. PMID- 11197090 TI - A comparison of health needs and personal health goals of Army Reserve Military and civilian employees. AB - Army active and reserve component personnel must be ready for rapid mobilization as world conflicts increase in number and intensity. Department of Defense civilian employees also need to be available to work long hours to maintain troop support. Healthy lifestyles are key to the physical and mental readiness demanded by this kind of work. The purpose of this descriptive study was to assess health and readiness by examining the health needs, identified through health risk appraisals, and personal health goals of military personnel and civilians (N = 90) employed at a large Army Reserve command headquarters located in the southern part of the country. Prominent health needs included reducing the number of saturated fats found in the diets of military personnel and increasing the frequency of exercise for civilian employees. Weight loss constituted the primary personal health goal for 53% of all employees. Initial health promotion activities should incorporate assessment information into the design of command sponsored programs. Focusing on health needs as well as personal health goals may enhance the early success of such programs. PMID- 11197091 TI - The effect of "mentored" relationships on satisfaction and intent to stay of company-grade U.S. Army Reserve nurses. AB - This study examined the strategic implications of mentoring relationships perceived by company-grade U.S. Army Reserve nurses. The effects of mentorship on professional socialization, job satisfaction, and intent to stay were examined using the adapted framework of Hunt and Michael. The study population consisted of U.S. Army Reserve nurses from all three components of the ready reserve. One hundred nurses from each category were randomly selected and provided a questionnaire. The questionnaire combined Dreher's Mentoring Scale, Price's Intent-to-Stay Scale, and Hoppock's Job Satisfaction Scale. The overall response rate was 57%. Seventy-two of the 171 respondents reported at least one mentored experience. Findings indicate that mentored nurses report more satisfaction and have a higher intent to stay than nonmentored nurses. Continued research and encouragement of mentoring are recommended. PMID- 11197092 TI - Mentoring experiences among Navy midshipmen. AB - Previous research suggests that mentor relationships are facilitative of career success, career satisfaction, and retention in organizations. Yet, little research has been done to explore the prevalence or function of mentor relationships in military populations. In this study, preliminary data were collected regarding the prevalence of mentor relationship experiences among 576 third year midshipmen at the U.S. Naval Academy. Only 40% of respondents had ever experienced a mentor relationship. Most mentors were senior military personnel, and 87% were male. Most relationships were mutually initiated, and they tended to last for several years. Although both career and psychosocial mentor functions were present in these relationships, psychosocial functions were most notable and most highly correlated with positive appraisals of mentor relationships. Midshipmen viewed mentoring as extremely important and rated their own mentor relationships as extremely positive. Implications for further research on mentoring are discussed. PMID- 11197093 TI - Gender differences in the utilization of a military ship's medical department. AB - Civilian studies show roughly a three-fold higher use of medical resources by females of childbearing age than males. Significantly higher use of medical services by females would be important information when staffing and supplying U.S. Navy ships to accommodate female crew members. In this light, visits to the medical department on a ship with a mixed-gender crew were reviewed for a 6-month period. Total visits were counted by gender, and female visits were categorized. Females were seen at a rate 9.2 times that of males (6.44 vs. 0.70 visits per year). Gender-specific problems accounted for a minority of female visits (39%), whereas gender-neutral problems yielded a female-to-male visit ratio of nearly 6:1. At this rate, the work load of a ship's medical department will increase substantially when integrating women into an all-male crew. PMID- 11197094 TI - Operational medicine experience integrated into a military internal medicine residency curriculum. AB - The optimal training of physicians should prepare them for the environment in which they will practice. During the past several years, the practice of internal medicine has shifted from a focus on the inpatient setting to one that includes an emphasis on the ambulatory clinic. Military internists must be further prepared to practice medicine with forward units, at field hospitals, and in other operational settings. Community-based teaching programs that reflect present and future practice are increasingly recognized as essential, yet details on the structure and implementation of such programs, especially those designed to teach field and operational medicine, are lacking. The Internal Medicine Residency Program at Walter Reed Army Medical Center has developed and implemented an operational medicine curriculum that includes a field medical training exercise. The program is driven by the residents and chief resident and requires little additional funding. Resident research continues to increase, morale remains high, and the first class to complete the 3-year operational curriculum achieved a 100% pass rate on the American Board of Internal Medicine certification examination. We describe our 3-year experience of implementing this program, with an emphasis on curriculum design and execution, qualitative assessment, and initial lessons learned. PMID- 11197095 TI - A longitudinal subspecialty experience for internal medicine residents. AB - OBJECTIVE: Market and technology innovations have greatly changed the teaching and practice of medicine in the past 10 years. This report describes an innovation in the ambulatory education of internal medicine residents: a subspecialty continuity clinic. METHODS: A subspecialty continuity clinic was developed to improve the training of internal medicine residents in caring for complex ambulatory patients. The clinic structure is discussed from the perspective of patients, residents, and subspecialists. Logistical challenges and solutions are described. RESULTS: Two and one-half years into the program, feedback from residents and subspecialists has been positive. In-training examination scores are relatively higher in the involved specialties, and residents are managing illnesses they rarely saw in an outpatient setting before this program. CONCLUSION: This experience suggests that a subspecialty continuity clinic is worthwhile and practical in educating primary care residents. PMID- 11197096 TI - Attack on Koreyni-Both's article. PMID- 11197097 TI - Evaluation of psychopathological factors and origins of suicides committed by soldiers, 1989 to 1998. AB - Research and scientific observations indicate that, in the armed forces, some individuals tend to experience strong feelings of solitude and harm and do not always have opportunities to receive help. The inability to solve and successfully cope with problems may lead to adaptive difficulties and provoke reckless reactions, including suicide attempts. The aim of this project was a retrospective analysis of the origins and factors leading to successful suicide attempts undertaken by soldiers from 1989 to 1998, with special emphasis on psychopathological determinants. The study examined all cases of successful suicides in the Polish Armed Forces: 163 professional soldiers (military service was their job) and 274 privates (obligatory military service group). The most common reason for suicides in the analyzed group was the combination of psychiatric disorders and psychosocial factors. Among privates, most of the suicides occurred during the first 12 months of service, whereas professional soldiers committed most suicides between their 11th and 15th years of service. The results suggest the urgent introduction of a suicide prevention program. PMID- 11197099 TI - Prevalence and contributing factors of eating disorder behaviors in active duty service women in the Army, Navy, Air Force, and Marines. AB - Eating disorders continue to be studied among civilian women. Gross disturbances in eating behaviors characterize the condition of anorexia nervosa (AN), currently seen among 1 to 2% of non-active duty women. Bulimia nervosa (BN) is prevalent among 2% of the female population, and both disorders have a female-to male ratios of 10:1. Another category of eating disorders known as not otherwise specified (NOS) occurs in 3 to 35% of individuals in the reported literature. This study examined the prevalence of AN, BN, and NOS among a large sample of active duty women currently serving in the Army, Navy, Air Force, and Marines. Multiple military, professional, and behavioral variables were analyzed to provide an increased understanding and awareness of these disorders among all active duty service women. This descriptive, correlational study of 3,613 service women targeted females from the total population of three major medical centers (Army, Navy, and Air Force) and the total population of Marine women serving in Okinawa, Japan, at the time of the study. Anonymous survey return was obtained at 34% (N = 1,278). The study revealed an overall prevalence of 1.1% for AN, 8.1% for BN, and 62.8% for NOS among all service women. However, AN, BN, and NOS were found at significantly higher rates (p = 0.000) among women in the Marines, who reported AN at 4.9%, BN at 15.9%, and NOS at 76.7%. Use of laxatives, diuretics, diet pills, vomiting, and fasting for standards increased during the body measurement and fitness periods for all services, but year-round use of many of these behaviors occurred at significantly higher rates among Marines (p = 0.000). Multiple logistic regression analysis predicted several factors associated with the manifestation of eating disorders in this population of active duty women. PMID- 11197098 TI - Community meetings on a military inpatient psychiatric unit: a question of balance. AB - Community meetings are a mainstay of any inpatient psychiatric unit. Although they differ in frequency, attendance, leadership, and size, they all maintain a similar purpose of acculturating the members to the values of the ward and encouraging responsible behavior and effective communication. The military inpatient psychiatric unit is no different, although it does have several unique factors that affect the management of the community meeting. Specifically, these factors are the inherent military rank structure, which often conflicts with the rank of staff and other patients, the incorporation of a civilian population into a military culture, and a greater focus on patient transitions from military to civilian society. We describe and discuss the common variables of community meetings, elucidate how the military aspects affect the meeting, and offer potential suggestions for the management of this unique large dynamic group. PMID- 11197100 TI - Organization and work of the war hospital in Tomislavgrad during the war in Bosnia and Herzegovina from 1992 to 1995. AB - The work of the War Hospital in Tomislavgrad during the war in Bosnia and Herzegovina from 1992 to 1995 is described. The War Hospital in Tomislavgrad was one of the first medical institutions organized in Bosnia and Herzegovina, with the intention of providing surgical treatment and care to soldiers, local civilians, and refugees who found shelter in this part of the country. It was located on the main communication route connecting Bosnia and Herzegovina and the south part of Croatia. During the 4-year period, 23,191 examinations, of which 8,341 were first-time examinations, and 1,547 surgical operations were performed. The hospital provided a high level of surgical and anesthesiology service in an area where none existed before the war. All patients were treated regardless of their nationality or religion, thus mitigating the consequences of the war. PMID- 11197101 TI - Vision readiness of the reserve forces of the U.S. Army. AB - In 1996 and 1997, the Army conducted an exercise to assess the ability to rapidly mobilize the reserve forces. In accordance with Army requirements, each soldier was evaluated to determine if he or she met vision and optical readiness standards. Of the 1,947 individuals processed through the optometry section, 40% met vision requirements without correction and 32% met vision requirements with their current spectacles. The remaining 28% required examination. A major impediment to processing reserve units for deployment is the lack of vision and optical readiness. In the mobilization for the Persian Gulf War, significant delays were incurred because of the time required to perform eye examinations and fabricate eyewear. However, as a result of this exercise, current prescriptions will be available in the event of mobilization. To ensure readiness, all units should perform such exercises periodically. PMID- 11197102 TI - Ocular injuries caused by mustard gas: diagnosis, treatment, and medical defense. AB - Sulfur mustard has been used as a vesicant chemical warfare agent. To investigate the ocular damage it causes, we studied the effects on chemical casualties in the Iran-Iraq War. The patient population consisted of more than 5,000 chemical casualties, both military and civilian. The range of ocular damage was wide. The most common ocular effects were conjunctivitis and photophobia. Patients with significant corneal involvement are at risk for corneal ulceration and rarely for anterior chamber scarring and neovascularization, any of which would result in prolonged disability. In conclusion, the eye is the organ most sensitive to sulfur mustard vapor. Ocular injuries generally heal completely. In severe cases, blindness may occur. The need for corneal transplantation is rare. PMID- 11197103 TI - Initial 67th Combat Support Hospital Optometry Services in Taszar, Hungary, during Operation Joint Endeavor. AB - BACKGROUND: Existing U.S. Army personnel and equipment authorization documents do not recognize the need for optometry services at deployed combat support hospitals (CSHs). The specific hospital tasked with the mission of supporting Operation Joint Endeavor from a support base in Taszar, Hungary, did not have any documentation authorizing the assignment of ophthalmology assets. Current Army doctrine stipulates the presence of an area support medical battalion, with assigned optometry assets, to deploy and operate near a CSH. However, in the winter of 1995, when Operation Joint Endeavor began, there were no area support medical battalions staffed in Europe, and none deployed to the Taszar support base. Therefore, the 67th CSH's mission to provide comprehensive inpatient and outpatient care on a contingency basis to all personnel in the area of operations did not have a doctrinal means of supporting an eye care requirement. OBJECTIVE: To meet this eye care shortfall between doctrinal policy and actual operational needs or requirements, the optometry staff of the 67th CSH scavenged two optometry field sets from old Operation Desert Storm war stock and deployed with the main body of hospital personnel to Taszar, Hungary, on December 18, 1995. In doing so, the Table of Organization and Equipment was thus supplemented with extra equipment and personnel, beyond doctrinal guidelines, to accomplish the assigned mission. METHOD: This report is a prospectively gathered summary of the eye care provided from December 18, 1995, to September 15, 1996. RESULTS: A total of 1,471 patients were examined and treated, averaging 7 patients per day. Less than half of the case load was medical in nature, with the remaining being refractive in nature or for periodic examination. The most common pathologies seen were soft contact lens complications, non-contact lens corneal pathology, conjunctivitis (bacterial, viral, and adenoviral), and ocular trauma (foreign bodies, chemical splashes, blunt injury). Refractive cases during the entire deployment involved primarily myopes requiring increased correction. However, close to half of the refractive cases in the first month involved habitually uncorrected low hyperopes and early presbyopes. CONCLUSIONS: Based on the productivity presented by the case load demand of this CSH's area medical support mission, an eye care need was clearly met, adding to the overall mission success of the 67th CSH. PMID- 11197104 TI - A comparison of morbidity in the Australian Defence Force with Australian general practice. AB - This study was designed to examine morbidity patterns among Australian Defence Forces members and to compare them with civilian general practice. The study was conducted in the outpatient departments of the Royal Australian Air Force (RAAF) No. 6 Hospital, Melbourne, Australia. The patients studied were male and female members of the RAAF (66%), Army (25%), and Navy (9%). The problems managed at all primary care consultations during 1993 and 1994 were coded using the Ninth Revision of the International Classification of Diseases (Clinical Modification). The codes were grouped and compared against a major study of Australian general practice. In the 6 Hospital study, 21,910 problems were managed at 19,909 consultations. The main differences found between the two studies were that service personnel had more medical examinations, more musculoskeletal and respiratory problems, and fewer psychological and cardiovascular problems. Most of the differences observed may reflect the Defence Force's recruitment selection criteria and the emphasis on physical fitness and diet. PMID- 11197105 TI - Proposed technique for evaluation of endotracheal tube fixation and comparison of four fixation methods. AB - BACKGROUND: The fixation of an endotracheal tube must be rapid in conditions involving numerous casualties, such as a chemical warfare (CW) situation. The tube also should be fixed and strong to prevent unplanned extubations. METHODS: We developed a technique for the evaluation of fixation methods. This technique was used to evaluate four methods. Three commercial fixators were compared with the fixation method used today in the Israeli Defense Forces (IDF) and commonly used in different out-of-hospital settings. The exercises were performed on adult intubation mannequins with and without CW protective gear. The fixations were timed, and their quality was evaluated by the participants and inspectors. RESULTS: The time score for the method used today in the IDF was significantly higher compared with the commercial fixation methods. The quality scores for the Thomas fixator and the IDF method were significantly higher than for the fixators by VBM and Rusch. The CW protective gear significantly prolonged the time but did not affect the quality of the fixation. CONCLUSIONS: With this technique, a good estimation of the time and quality of fixation can be achieved. PMID- 11197106 TI - Periodontal disease and its association with systemic disease. AB - Periodontal diseases are oral disorders characterized by inflammation of the supporting tissues of the teeth. Usually, periodontitis is a progressively destructive loss of bone and periodontal ligament (loss of the attachment apparatus of the teeth). Periodontitis has documented risk factors, including but not limited to specific plaque bacteria, smoking, and diabetes mellitus. Initially, the link between systemic disease and periodontal diseases was thought to be unidirectional. Currently, there is increasing evidence that the relationship between these entities may be bidirectional. Recent case-control and cross-sectional studies indicate that periodontitis may confer a 7-fold increase in risk for preterm low birth weight infants and a 2-fold increase in risk for cardiovascular disease. These early reports indicate the potential association between systemic and oral health. Additionally, these studies support the central hypothesis that periodontal disease involves both a local and a systemic host inflammatory response. This knowledge of disease interrelationships may prove vital in intervention strategies to reduce patient risks and prevent systemic disease outcomes. Based on the current evidence of the periodontal-systemic disease connection, the purpose of this report is to help establish the groundwork for closer communication between physicians and periodontists in the military health care setting. PMID- 11197107 TI - Surgical care in the isolated military hospital. AB - BACKGROUND: To maintain the health of service members and their families throughout the world, the Department of Defense has established several isolated military hospitals (IHs). The operational environment of IHs is such that illness and traumatic injury requiring surgical intervention is common. This study sought to examine the general and orthopedic surgical experience at an IH to determine whether surgical care could be provided in an effective and safe manner. METHODS: All patients evaluated by the general and orthopedic surgeon at Guantanamo Bay Naval Hospital from October 1, 1998, to April 1, 1999, were included in this study. The following data were retrospectively reviewed: patient demographic data, diagnosis, initial and follow-up care, medical evacuation data, operative procedures, and complications. RESULTS: There were 336 patients who presented for surgical evaluation, resulting in 660 follow-up appointments during the study period. There were 31 medical evacuations (3 emergent). The surgical services performed 122 major operative procedures. There were 58 inpatient admissions. There was 1 death, and surgical complications occurred in 2 patients, for an overall morbidity and mortality of 1.4% and 0.7%, respectively. CONCLUSION: Our data show that an IH is capable of providing surgical care, including care for traumatic injuries, in a safe manner. This is the first study that provides objective evidence that general and orthopedic surgery at an IH can be provided within the standard of care. PMID- 11197108 TI - Heat stroke. PMID- 11197109 TI - Poliomyelitis: the role of military in the final campaign. PMID- 11197110 TI - Radiofrequency volumetric tissue reduction (RFVTR) of inferior turbinates: a new method in the treatment of chronic nasal obstruction. AB - Twenty-two Caucasians (16 male and 6 female) with chronic bilateral nasal obstruction due to hypertrophic inferior turbinates were followed up over a three month period. They were assessed by clinical examination, as active anterior rhinometry, and acoustic rhinometry before and after topical decongestion, preoperatively and three months after surgery. All patients were treated by application of radiofrequency-volumetric-tissue reduction (RFVTR, or somnoplasty) to both inferior turbinates. Initial postoperative edematous response disappeared during the first week after RFVTR. Three months postoperatively 20 of 22 patients (91%) reported subjective improvement of nasal patency. The average cross sectional area for both sides of the nasal cavity (measured at the head of the inferior turbinate (C-Notch) before decongestion) increased in 15 of 22 patients (68.2%). This means a significant improvement from 1.24 to 1.49 cm2 for both sides of the nasal cavity (p = 0.0054). We conclude that RFVTR can safely reduce turbinate volume in a precise manner in patients with nasal obstruction due to hypertrophic inferior turbinates. PMID- 11197111 TI - Stereotactic computer-assisted navigational sinus surgery: accuracy of an electromagnetic tracking system with the tissue debrider and when utilizing different headsets for the same patient. AB - The InstaTrak system by Visualization Technologies, Inc. (Woburn, MA) has recently introduced attachments that can be utilized to localize the tip of the XPS Straightshot debrider (Xomed Industries, Jacksonville, FL) during image guided surgery. The accuracy of these newer attachments has not been objectively tested in a clinical setting. Our primary objective was to compare the actual instrument (XPS debrider tip) location with its computer screen location in the coronal, sagittal, and axial views. This was considered to be the "accuracy" of the instrument being tested. We secondarily compared its accuracy with the accuracy of the 0 degree and 45 degrees curved localizing aspirators in a prospective study. The manufacturer also recommends that the same headset used during scanning be utilized during surgery. A second objective therefore was to determine if a headset other than the one used during CT scanning could be used intraoperatively with an acceptable level of accuracy. Accuracy of the instruments between the patients' own headset (used during CT scanning) and a generic or research headset (not used during scanning) was compared intraoperatively. The third and final objective was to determine if the same headset could be used repeatedly with an acceptable level of accuracy. Generic "research" headsets were therefore utilized for a total of five surgeries per headset and visual accuracy between the multiply utilized research headsets and the patients' own headsets was recorded and compared. Anatomic localization accuracy was 1.06 mm for the XPS debrider, 0.89 mm for the 0 degree aspirator, and 1.05 mm for the 45 aspirator when the patients own headset was utilized. When the research (generic) headset was utilized the respective values were 0.69 mm for the debrider, 0.77 mm for the 0 degree aspirator, and 0.99 mm for the 45 degrees aspirator. With multiple utilization of a single headset, there was no significant loss in accuracy. In conclusion, the accuracy of the newly marketed attachment for the debrider was found to be comparable to the standard aspirators. Accuracy remained acceptable when a headset other than the one used during CT scanning was used intraoperatively. No loss in accuracy was noted when a headset was utilized more than once. PMID- 11197112 TI - Interleukin-1 beta, interleukin-5, interleukin-6, interleukin-8, and tumor necrosis factor-alpha in chronic sinusitis: response to systemic corticosteroids. AB - Recently, the role of various cytokines in the pathogenesis of chronic rhinosinusitis has come under investigation. Various studies have reported increased levels of interleukin-3, interleukin-4, interleukin-5, interleukin-13, and granulocyte macrophage-colony stimulating factor in the sinonasal mucosa of patients with chronic rhinosinusitis. The present study investigated the levels of pro-inflammatory cytokines, including interleukin-1 beta (IL-1 beta), interleukin-5 (IL-5), interleukin-6 (IL-6) interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha), in the sinonasal mucosa of patients with chronic rhinosinusitis, and evaluated the response of these cytokines to oral corticosteroids. Chronic rhinosinusitis subjects (n = 15) and control subjects (n = 9) underwent nasal endoscopy and biopsy of the sinonasal mucosa. Chronic rhinosinusitis subjects were subsequently treated with a 10-day tapering dose of prednisone followed by a second sinonasal endoscopic exam and biopsy. Mucosal biopsy specimens were immunostained for IL-1 beta, IL-5, IL-6, IL-8, and TNF-a. In chronic rhinosinusitis subjects, mucosal levels of IL-1 beta, IL-6, IL-8, and TNF-alpha were significantly elevated when compared with control subjects, and levels of IL-5 demonstrated a strong trend toward elevation. In posttreatment chronic rhinosinusitis subjects, levels of IL-6 were significantly decreased when compared with pretreatment levels, and TNF-alpha levels demonstrated a significant trend toward reduction. These findings support the hypothesis that the inflammatory response in chronic rhinosinusitis is associated with elevated levels of pro-inflammatory cytokines, and suggest that oral corticosteroids may exert a beneficial effect by significantly reducing the levels of IL-6 and TNF alpha. PMID- 11197113 TI - Nasal mucociliary transport in pregnancy. AB - Using the saccharin method, we performed tests of mucociliary function four times during pregnancy and once one month after delivery in 27 women. As the transport distance for saccharin varied from 37 to 65 mm, we used the transport speed for evaluation. Pregnancy rhinitis affects at least 20% of pregnancies. The mucociliary transport speed was higher in the group of women with pregnancy rhinitis, and was reduced during pregnancy in the group of women without that condition. We found no significant correlation between mucociliary transport speed and objectively registered nasal peak expiratory flow index. The pathophysiology of pregnancy rhinitis is not known, but is possibly multifactorial. The changes occurring in the nasal mucociliary transport system during normal pregnancy and in pregnancy rhinitis need further studies. PMID- 11197114 TI - Endoscopic sinus surgery in patients with cystic fibrosis: an analysis of complications. AB - The application of endoscopic sinus surgery (ESS) for the management of paranasal sinus disease in patients with cystic fibrosis (CF) has been well described. Due to underlying medical issues such as acquired coagulopathies and advanced pulmonary disease, perioperative morbidity is assumed to be higher in this group. The incidence and type of complications associated with CF patients undergoing ESS has not been previously described. We reviewed 52 consecutive endoscopic procedures in 41 patients with CF performed by a single surgeon over a 34-month period. This review focused on perioperative and postoperative complications. Additional clinical data gathered included estimated blood loss, length of procedure, coagulation laboratory studies, the presence of nasal polyposis, the use of nasal packing, pulmonary function status, and average hospitalization time. A total of six complications were identified--four immediate and two delayed. The perioperative or immediate complications included two cases of epistaxis, one case of periorbital ecchymosis, and one case of pulmonary hemorrhage. Delayed complications include one case of epistaxis and one case of intranasal scarring. In two of these six patients, length of hospitalization was prolonged for management of the associated complications. No study has specifically addressed complications of ESS in the CF patient. Our review demonstrates a complication rate of 11.5%, which compares favorably with the non CF ESS complication rates of 0-17% reported in the literature. Critical to successful management of these patients is coordinated care delivered by the pediatrician or internist, the pulmonary specialist, the anesthesia team, and the otolaryngologist. In addition to a review of current literature, we discuss the overall management approach adopted at our institution and highlight elements thought to minimize morbidity. PMID- 11197115 TI - Acanthamoeba rhinosinusitis: characterization, diagnosis, and treatment. AB - Nasal and paranasal sinus manifestations are among the most common presentations of the acquired immunodeficiency syndrome (AIDS). Several studies cite that as many as 70% of patients with this disease have symptoms referable to the head and neck, including a 30% prevalence of sinusitis. Although the bacteriology of sinusitis in this population is largely considered comparable to that of immunocompetent patients, several opportunistic pathogens have been identified, particularly when T-cell counts are low. This report identifies Acanthamoeba as a potentially fatal cause of rhinosinusitis in immunosuppressed patients. The pathogenesis, diagnosis, and treatment of this rare entity will be discussed and the literature reviewed. PMID- 11197116 TI - Frontal sinus surgery: endoscopic technique and preliminary results. AB - Endoscopic frontal sinus surgery, once the last frontier in the evolution of endoscopic sinus surgery, is considered difficult, risky to the patient, and likely to result in a high failure rate. We clarify the surgical anatomy for frontal sinus surgery that, based on a review of our data, provides safe and predictable access to the frontal sinus. We studied 200 consecutive patients with respect to indications, endoscopic and radiographic findings, results, and complications. The study will describe the technique in detail, including the following points: 1) computed tomography identification of the superior attachment of the uncinate process; 2) complete removal of the uncinate process, including its superior attachments, by using the microdebrider; 3) removal of the agger nasi cell, if present; and 4) verification of an open frontal sinus by a transillumination or image-guided system. Postoperative assessment of patients' symptoms and the confirmation of a patent frontal sinus by office endoscopy and transillumination indicated a 90% patency for short-term follow-up (average 12.2 months). There were no major complications. Postoperative complications included frontal recess stenosis, polypoid mucosa occluding the frontal recess, and middle turbinate lateralization. All of these situations may lead to recurrence of infection and symptoms. In-depth understanding of anatomic variations of the uncinate process and precise surgical removal of its superior attachments provide surgical access to the frontal sinus that is based on the natural ostia and is, therefore, more likely to remain patent. PMID- 11197117 TI - Effect of topical nasal pharmaceuticals on sodium and chloride transport by human airway epithelia. AB - The human airway epithelium lines the respiratory tract from the nasal mucosa to the bronchioles. Electrolyte transport by these epithelia is crucial in maintaining the appropriate volume and salt composition of the airway surface fluid. When this epithelium becomes functionally impaired, the airways are more prone to respiratory infections. We studied the effect of six common topical agents that are commonly used to treat rhinorrhea and nasal inflammation on the transepithelial resistance, sodium, and chloride transport of primary cultures of human airway epithelia grown at the air-liquid interface. The pharmaceuticals fluticasone propionate, cromolyn sodium, ipratropium bromide, azelastine, oxymetazoline, and normal saline were used and the electrical function of the epithelia was studied in Ussing chambers. Azelastin and ipratropium bromide treated epithelia were found to have a significant decrease in transepithelial resistance. Both normal saline and fluticasone propionate resulted in significant increases in amiloride-sensitive short circuit currents that reflect sodium transport. Finally, normal saline resulted in a significant increase in bumetanide-sensitive short circuit current that reflects chloride transport across the epithelia. The data presented may explain a mechanism by which some topical pharmaceuticals help reduce rhinorrhea, and may point to some unwanted side effects of some pharmaceuticals on the electrolyte transport of the airway epithelia. In summary, several of the common topical nasal agents alter the electrolyte transport of the nasal airway epithelia. The in vivo significance of these findings is to be determined. PMID- 11197118 TI - Subacute effects of ozone exposure on cultivated human respiratory mucosa. AB - This study was designed to investigate subacute effects of long-term exposure of both healthy and chronically inflamed human respiratory mucosa to ozone. Functional and metabolic effects on ciliary beat frequency (CBF), release of interleukin 8 (IL-8), interleukin 4 (IL-4), and gamma interferon (g-INF), as well as cellular viability and cytotoxicity, were monitored. Cell cultures of 60 specimens (healthy mucosa: n = 30, inflamed mucosa: n = 30) were exposed to synthetic air and to ozone-enriched synthetic air in different concentrations of 100, 500, and 1000 micrograms/m3. Continuous expositions were performed using an air/liquid interface cell culture technique for a period of 4 weeks. CBF was monitored using video-interference contrast microscopy and cytokine release was quantified by enzyme immunoassays. Cellular viability and cytotoxicity were controlled by measuring lactate dehydrogenase activity, cytosolic activity of esterases, and by staining of nuclear DNA. Synthetic air had no influence on CBF during the 4 weeks of exposure. IL-8 release was continuously diminished in unaffected and in chronically inflamed mucosa. Within the first week of continuous exposure with any ozone concentration neither CBF nor release of IL-8 were affected in healthy or in inflamed mucosa. During the second and the following weeks of exposure CBF and the release of IL-8 were reduced in both tissues. Release of IL-4 or g-INF were not detectable at any time during the 4 weeks of ozone exposure. At higher ozone concentrations of 500 and 1000 micrograms/m3 there was an increase of cytotoxicity which was greater in chronically inflamed than in healthy mucosa. In conclusion, ozone had no measurable effect on those parameters measured in human upper respiratory epithelium after one week of in vitro exposure to different concentrations, but did after longer periods of exposure. Chronically inflamed mucosa had a tendency toward a higher susceptibility to intermediate and high concentrations of ozone that did not reach a level of statistical significance under the conditions used in this study. PMID- 11197119 TI - Biologic characteristics of paragangliomas of the nasal cavity and paranasal sinuses. AB - Paragangliomas of the nasal cavity and paranasal sinuses are extremely rare. This study was conducted to investigate the biologic characteristics of these lesions on different molecular levels and to estimate their biologic behavior. Operative specimens of three patients who underwent surgery for a paraganglioma of the nasal cavity (one case) or paranasal sinuses (two cases) were investigated by routine histology, quantitative DNA analysis, and immunohistochemical assessment of proliferation markers (i.e., Proliferating Cell Nuclear Antigen, PCNA; Ki67 MIB-1), the expression of cell-surface antigens, which reflect the tumor-stroma interaction (i.e., CD 44 v0.4/5 and 6, CD 54, CD 106), oncogene products (nm-23; p53), and bcl-2 as a marker of apoptosis. Histologically, two tumors were paragangliomas of the adenomatous subtype, one lesion was classified as angiomatous. According to DNA analysis, aneuploid cells were detected in all tumors. Two of three paragangliomas were classified as a DNA type III pattern, implying a high percentage of aneuploid cells and an aggressive behavior. Immunohistochemically, paragangliomas of the nasal cavity showed increased scores for both proliferation markers tested, indicating a rapid growth pattern. According to the expression of cell-surface markers and oncogene products, these tumors displayed an aggressive behavior and an infiltrating growth pattern. The highest value for the parameters of quantitative DNA analysis and highest proliferation scores were found in a tumor of a patient who developed multiple tumor recurrences after radical excision of the lesion with clear margins, and finally died of disease. In conclusion, paragangliomas of the nasal cavity and paranasal sinuses examined in this study should be regarded as suspicious concerning their biologic and clinical behavior. Radical excision, and in cases with highly aggressive biology, postoperative radiation therapy are recommended. Tumor biologic examinations can help to recognize high-risk patients for developing recurrences and possibly lesions with a malignant behavior and to enhance our understanding of the biology of these extremely rare tumors of the nasal cavity and paranasal sinuses. PMID- 11197120 TI - Malignant fibrous histiocytoma of the nasal cavity and paranasal sinuses. AB - Malignant fibrous histiocytomas are uncommon in the head and neck, the sinonasal tract being the most common location. This report describes 5 cases in this area: two in the nasal cavity, two in the maxillary sinus, and one in the frontal sinus. Four were primary cases and one was secondary to previous irradiation. All patients received surgical treatment, one of them with postoperative irradiation. All five patients experienced local recurrences and three also experienced distant metastases. Only one of these recurrences was successfully salvaged and the patient is alive and free of disease 3 years after resection. A summary of knowledge about the entity is reviewed. PMID- 11197121 TI - Inheritance and variation in eggshell patterning in the great tit Parus major. AB - The inheritance of patterns on avian eggshells is central to understanding the evolution of traits such as egg mimicry (e.g. in cuckoos). Yet little is known about the inheritance, or indeed function, of eggshell patterns. It has long been believed that the evolution of eggshell pattern mimicry required that patterns be determined by genes situated on the female-specific W chromosome. However, it has never been demonstrated for any bird that egg pattern traits (rather than ground colour) are female sex linked, or indeed that they are inherited. We studied the inheritance of three measures of egg-pigment patterns in a wild great tit population. Egg patterns were female specific but unrelated to female attributes such as age or condition and showed only weak environmental effects. Eggs of daughters resembled those of both their mothers and maternal grandmothers, but not of their paternal grandmothers. We conclude that this is the first demonstration of female sex-linked inheritance of avian eggshell patterning, so raising the probability that such a system operates in egg mimics and their hosts. PMID- 11197122 TI - Cryptic genetic variation and paraphyly in ravens. AB - Widespread species that are morphologically uniform may be likely to harbour cryptic genetic variation. Common ravens (Corvus corax) have an extensive range covering nearly the entire Northern Hemisphere, but show little discrete phenotypic variation. We obtained tissue samples from throughout much of this range and collected mitochondrial sequence and nuclear microsatellite data. Our study revealed a deep genetic break between ravens from the western United States and ravens from throughout the rest of the world. These two groups, the 'California clade' and the 'Holarctic clade' are well supported and over 4% divergent in mitochondrial coding sequence. Microsatellites also reveal significant differentiation between these two groups. Ravens from Minnesota, Maine and Alaska are more similar to ravens from Asia and Europe than they are to ravens from California. The two clades come in contact over a huge area of the western United States, with mixtures of the two mitochondrial groups present in Washington, Idaho and California. In addition, the restricted range Chihuahuan raven (Corvus cryptoleucus) of the south-west United States and Mexico is genetically nested within the paraphyletic common raven. Our findings suggest that the common raven may have formerly consisted of two allopatric groups that may be in the process of remerging. PMID- 11197123 TI - Waiting time to parapatric speciation. AB - Using a weak migration and weak mutation approximation, I studied the average waiting time to parapatric speciation. The description of reproductive isolation used is based on the classical Dobzhansky model and its recently proposed multilocus generalizations. The dynamics of parapatric speciation are modelled as a biased random walk performed by the average genetic distance between the residents and immigrants. If a small number of genetic changes is sufficient for complete reproductive isolation, mutation and random genetic drift alone can cause speciation on the time-scale of ten to 1,000 times the inverse of the mutation rate over a set of loci underlying reproductive isolation. Even relatively weak selection for local adaptation can dramatically decrease the waiting time to speciation. The actual duration of the parapatric speciation process (that is the duration of intermediate forms in the actual transition to a state of complete reproductive isolation) is shorter by orders of magnitude than the overall waiting time to speciation. For a wide range of parameter values, the actual duration of parapatric speciation is of the order of one over the mutation rate. In general, parapatric speciation is expected to be triggered by changes in the environment. PMID- 11197124 TI - Molecular and morphological evidence on the phylogeny of the Elephantidae. AB - The African and Asian elephants and the mammoth diverged ca. 4-6 million years ago and their phylogenetic relationship has been controversial. Morphological studies have suggested a mammoth Asian elephant relationship, while molecular studies have produced conflicting results. We obtained cytochrome b sequences of up to 545 base pairs from five mammoths, 14 Asian and eight African elephants. A high degree of polymorphism is detected within species. With a dugong sequence used as the outgroup, parsimony and maximum-likelihood analyses support a mammoth African elephant clade. As the dugong is a very distant outgroup, we employ likelihood analysis to root the tree with a molecular clock, and use bootstrap and Bayesian analyses to quantify the relative support for different topologies. The analyses support the mammoth African elephant relationship, although other trees cannot be rejected. Ancestral polymorphisms may have resulted in gene trees differing from the species phylogeny Examination of morphological data, especially from primitive fossil members, indicates that some supposed synapomorphies between the mammoth and Asian elephant are variable, others convergent or autapomorphous. A mammoth African elephant relationship is not excluded. Our results highlight the need, in both morphological and molecular phylogenetics, for multiple markers and close attention to within-taxon variation and outgroup selection. PMID- 11197125 TI - Axial and appendicular pneumaticity in Archaeopteryx. AB - From the time of its discovery in 1860 to this day Archaeopteryx has been essential to our understanding of avian evolution. Despite the great diversity of plesiomorphic avialan (sensu Gauthier 1986) taxa discovered within the last decade, Archaeopteryx remains the most basal avialan taxon. A very unusual feature of extant birds is their lung structure, in which air diverticulae penetrate the bones. This has previously been reported in Archaeopteryx as well, in the cervical vertebrae of the Berlin specimen and in an anterior thoracal vertebra of the Eichstatt specimen. This indicates the presence of a cervical air sac. We show that the London specimen also has pneumatized anterior thoracal vertebrae, and, thus, that this feature was present in the most archaic avialans, as the London and Eichstatt specimens are different species. Furthermore, the pelvis of the London specimen shows clear signs of the presence of an abdominal air sac, indicating that at least two of the five air sacs present in modern birds were also present in Archaeopteryx. Evidence of pubic pneumaticity was also found in the same position in some extant ratites. PMID- 11197126 TI - Are avian blood parasites pathogenic in the wild? A medication experiment in blue tits (Parus caeruleus). AB - The Hamilton and Zuk hypothesis on haemoparasite-mediated sexual selection and certain studies of reproductive costs are based on the assumption that avian blood parasite infections are detrimental to their hosts. However, there is no experimental evidence demonstrating harmful effects of blood parasites on fitness in wild populations, it even having been suggested that they may be non pathogenic. Only an experimental manipulation of natural blood parasite loads may reveal their harmful effects. In this field experiment we reduced through medication the intensity of infection by Haemoproteus majoris and the prevalence of infection by Leucocytoazoon majoris in blue tits (Parus caeruleus), and demonstrated detrimental effects of natural levels of infection by these common parasite species on host reproductive success and condition. The fact that some of the costs of infection were paid by offspring indicates that blood parasites reduce parental working capacity while feeding nestlings. Medicated females may be able to devote more resources to parental care through being released from the drain imposed upon them by parasites and/or through a reduced allocation to an immune response. Therefore, this work adds support to previous findings relating hosts' life-history traits and haematozoan infections. PMID- 11197127 TI - Antigenic role of the endosymbionts of filarial nematodes: IgG response against the Wolbachia surface protein in cats infected with Dirofilaria immitis. AB - Filarial nematodes harbour intracellular endosymbiotic bacteria, which have been assigned to the genus Wolbachia. These bacteria appear to play an important role in the pathogenesis of filarial diseases through their lipopolysaccharides. In view of the presence of Wolbachia endosymbionts in the body of filarial nematodes, one might also expect that proteins from these bacteria play an antigenic role in humans and animals affected by filariases. To test this hypothesis, we produced in recombinant form the surface protein WSP and a portion of the cell-cycle protein FTSZ from the Wolbachia of Dirofilaria immitis. Western immunoblot assays were then performed using cat sera to test the immunogenicity of these proteins. Sera were collected from owners' cats, which were either sero negative or sero-positive for D. immitis and from cats before and after experimental infection with D. immitis. FTSZ was recognized in Western blots by sera from both positive and negative cats and from both uninfected and experimentally infected cats. WSP was recognized only by sera from positive cats and from cats experimentally infected with D. immitis; this protein was not recognized by sera from negative cats and from cats before experimental infection with D. immitis. The results of Western blot assays on WSP thus support the hypothesis that infection with filarial nematodes induces the production of antibodies against Wolbachia proteins. PMID- 11197128 TI - Intraspecific phylogenetic congruence among multiple symbiont genomes. AB - Eukaryotes often form intimate endosymbioses with prokaryotic organisms. Cases in which these symbionts are transmitted cytoplasmically to host progeny create the potential for co-speciation or congruent evolution among the distinct genomes of these partners. If symbionts do not move horizontally between different eukaryotic hosts, strict phylogenetic congruence of their genomes is predicted and should extend to relationships within a single host species. Conversely, even rare 'host shifts' among closely related lineages should yield conflicting tree topologies at the intraspecific level. Here, we investigate the historical associations among four symbiotic genomes residing within an aphid host: the mitochondrial DNA of Uroleucon ambrosiae aphids, the bacterial chromosome of their Buchnera bacterial endosymbionts, and two plasmids associated with Buchnera. DNA sequence polymorphisms provided a significant phylogenetic signal and no homoplasy for each data set, yielding completely and significantly congruent phylogenies for these four genomes and no evidence of horizontal transmission. This study thus provides the first evidence for strictly vertical transmission and 'co-speciation' of symbiotic organisms at the intraspecific level, and represents the lowest phylogenetic level at which such coevolution has been demonstrated. These results may reflect the obligate nature of this intimate mutualism and indicate opportunities for adaptive coevolution among linked symbiont genomes. PMID- 11197129 TI - A mechanistic link between parasite resistance and expression of a sexually selected trait in a damselfly. AB - This paper examines a field-based insect system in which a signal trait and an immune effector system responsible for parasite resistance rely on the same melanin-producing enzyme cascade (phenoloxidase, PO). Observations and experiments on males of the calopterygid damselfly Calopteryx splendens xanthostoma revealed that resistance to the prevalent parasite in the study system (a eugregarine protozoan infecting the mid-gut) was correlated with quantitative aspects of the sexually dimorphic melanized wingspot of males, a trait that is produced and fixed before the host comes into contact with the sporozsoites of the parasite. Regulation of PO during experimental immune challenge showed that males with dark, homogenous melanin distribution in their wings showed no change in PO levels 24 h after challenge. By contrast males with lighter and/or more heterogenous melanin distribution in their wings tended to show higher PO levels 2-h after immune challenge. The changes in PO levels occur despite the lack of a relationship between wing-pigment distribution and the cellular encapsulation response. These results suggest a shared, limiting resource may form the mechanistic basis of the trade-off between a condition dependent signal trait and immune function in this system. PMID- 11197130 TI - Human fertility variation, size-related obstetrical performance and the evolution of sexual stature dimorphism. AB - In several animal species, change in sexual size dimorphism is a correlated response to selection on fecundity. In humans, different hypotheses have been proposed to explain the variation of sexual dimorphism in stature, but no consensus has yet emerged. In this paper, we evaluate from a theoretical and an empirical point of view the hypothesis that the extent of sexual dimorphism in human populations results from the interaction between fertility and size-related obstetric complications. We first developed an optimal evolutionary model based on extensive simulations and then we performed a comparative analysis for a total set of 38 countries worldwide. Our optimization modelling shows that size-related mortality factors do indeed have the potential to affect the extent of sexual stature dimorphism. Comparative analysis using generalized linear modelling supports the idea that maternal death caused by deliveries and complications of pregnancy (a variable known to be size related) could be a key determinant explaining variation in sexual stature dimorphism across populations. We discuss our results in relation to other hypotheses on the evolution of sexual stature dimorphism in humans. PMID- 11197131 TI - 'Sloppy' sperm mixing and intraspecific variation in sperm precedence (P2) patterns. AB - Sperm precedence patterns are typically highly variable within (and between) species. Intraspecific variation in sperm precedence (measured as P2, the proportion of progeny fathered by the last male to mate' is frequently seen as a candidate for adaptive interpretation through either male effects (e.g. body size), female effects (e.g. cryptic female choice) or an interaction between the two. Here we show, using computer simulation, that if ejaculates divide into a number of 'packets' and packets from two males mix randomly, then a variety of patterns of sperm precedence may result. We term this process 'sloppy' mixing. If ejaculates break into a small number of packets, bimodal P2 distributions are predicted. As the number of packets is increased, then a complex series of changes through multimodal and flat to unimodal distributions results. Sloppy mixing can thus result in many of the observed P2 distributions. Sloppy mixing is unlikely to change the predictions of adaptive models of sperm competition. PMID- 11197132 TI - Extra-pair paternity as the result of reproductive transactions between paired mates. AB - Transactional ('optimal skew' or concessions') models of social evolution emphasize that dominant members of society can be favoured for donating parcels of reproduction to same-sexed subordinates in return for cooperation by the latter. We developed a mathematically similar model in which extra-pair paternity in broods receiving biparental care is viewed as emerging from a reproductive transaction between the paired mates. The model quantitatively predicted the maximum paternity that a male mate can demand before its female mate is favoured to break the pair bond and caring solitarily for a brood sired entirely by a neighbouring male. The model predicts that extra-pair paternity results when the neighbouring male is of sufficiently higher quality than the male mate. In such cases, the exact amount of extra-pair paternity will vary directly with the difference in quality between the two males and inversely with the value (fitness impact) of the male mate's parental care. Importantly, the transactional model provided a unified explanation for experimental and observational evidence that extra-pair paternity rises with decreasing quality of the male mate, increasing genetic variability among breeding males, increasing breeding density, increasing availability of food and decreasing involvement of the male mate in parental care. PMID- 11197133 TI - Male-male competition and parental care in collared flycatchers (Ficedula albicollis): an experiment controlling for differences in territory quality. AB - Females are known to benefit from mate choice in several different ways but the relationship between these benefits has received little attention. The quality of resources provided by males, such as nest sites, and paternal care are often assumed to covary positively However, because the location of the nest affects the cost of parental care, these two benefits from mate choice can easily be confounded. To investigate the provisioning ability of successful competitors while controlling for differences in territory quality we removed early-settled pairs of collared flycatchers (Ficedula albicollis) and allowed replacement by later-arriving males or floaters (i.e.'poor competitors'). A control group of early-settled males (i.e. 'good competitors') had their females removed. Females paired to good competitors enjoyed a significantly higher reproductive success and tended to receive more parental assistance from their mates compared with females mated to poor competitors. Thus, some males seem able not only to compete successfully over resources but also to feed their offspring at a relatively higher rate. An alternative explanation, that poor competitors invested less in offspring quality in response to a lower share of paternity, could be rejected. The rate of extra-pair paternity did not differ between the two treatment groups. Our results suggest that male- male competition can sometimes facilitate female choice of superior care-givers. Thus, a female's benefit from choosing a competitive male may not be restricted to the quality of the resource he defends but can also include superior paternal care. PMID- 11197134 TI - Early exposure leads to repeatable preferences for male song in female zebra finches. AB - This study addressed the question of how early learning processes in females influence later preferences for a male trait. I tested whether exposure to song alone (of a male other than the father) was sufficient for inducing a stable (repeatable) preference in female zebra finches (Taeniopygia guttata) by limiting early exposure to tape tutoring. A group of controls heard no songs before also being tested in adulthood. Repeated tests for preferences for tutor or unfamiliar song were made, interspersed with additional tests involving new songs. Preferences were tested in an operant task where pecking of response keys led to song playback. Most females significantly preferred one of the two songs in a given test. In the first test, the relative preference for the tutor song was significantly higher for the tutored than for the control females. Subsequently, tutored females' preferences for the tutor song remained higher on average, but the two groups did not differ significantly. However, tutored, but not untutored females' preferences were highly repeatable between tests, suggesting that early exposure to song might lead to a consolidation ol choice behaviour, a previously unknown effect of early exposure to song in female songbirds. PMID- 11197136 TI - Protecting your records in an online world. PMID- 11197135 TI - Attentional diversion during adaptation affects the velocity as well as the duration of motion after-effects. AB - The effects of diverting attention on early motion processing in human vision were studied with a selective adaptation technique. The velocity of motion after effects (MAEs) produced on a stationary test grating after prolonged exposure to drifting luminance-modulated gratings was measured by matching MAE velocity with that of another physically moving grating. Initial MAE velocities decreased and their rate of decay increased with the distance of the adapting and test gratings from the fixation point. When attention was diverted from the adapting grating, by having subjects process the intermittently changing digit which formed the fixation point, initial MAE velocities were reduced and rate of decay increased, with the largest effect of diversion being found for gratings near the fixation point. The effects of varying attention mimic those of varying adapting duration, rather than adapting contrast or velocity, and appear to reflect a genuine change in motion-processing mechanisms. PMID- 11197137 TI - Searching the Web. The power of portals. PMID- 11197138 TI - Drug ads on TV: pretty, but perplexing. PMID- 11197139 TI - Wintertime common sense: how much do you have? PMID- 11197140 TI - Why are our children getting fat? PMID- 11197141 TI - St. John's Wort for wintertime blues. PMID- 11197142 TI - Winter sledding tips. PMID- 11197143 TI - Paying for prescriptions: programs that can help. PMID- 11197144 TI - Caring for a child with asthma. PMID- 11197145 TI - Necessity of monitoring HPLC by a X-R control chart on measurement of serum fat soluble vitamins. AB - In epidemiologic studies, many serum samples obtained from a large population have to be processed for measurement of fat-soluble vitamins. Quantification results by a high performance liquid chromatography (HPLC) should be stable in both intra- and inter-run, and a quality control may be performed by a X-R control chart. The present study shows that serum retinol, alpha-tocopherol, alpha-carotene, beta-carotene, and lycopene could be measured simultaneously, by 1) use of photodiode-array (POD) detector, 2) selection of some optimal analytical conditions (e.g. column, mobile phase, column temperature), 3) applying 2 internal standards, and 4) monitoring by a X-R control chart. The present procedure yielded relatively low coefficients of variations (CVs) compared to some reported figures. However, determination of CVs only does not ensure the accuracy and precision of an assay system, and application of a X-R control chart may be necessary for a good quality control of measurement, such as serum fat-soluble vitamins. PMID- 11197146 TI - Thoracoscopic lung biopsy for diffuse infiltrative lung disease. AB - Thoracoscopic lung biopsy is becoming the procedure of first choice for the diagnosis of many localized and diffuse lung diseases. We have performed thoracoscopic lung biopsy for 17 patients with diffuse infiltrative lung disease, in Kurume University Hospital. There were 13 females and 4 males with a mean age of 48 years (range: 19-71 years). Thoracoscopic surgical biopsy was performed in the right lung in 12 and in the left lung in 5. Adequate lung tissue from each case was obtained for pathological examination. The mean surgical biopsy time was 49 min (range: 25-72 min) and bleeding was negligible. The mean duration for chest tube drainage was 2.6 days. No postoperative complication such as prolonged air leakage occurred. A specific diagnosis from the biopsy was achieved in 13 (76.4%) of the 17 cases. In only 6 (35.2%) of the 17 cases, the pathological diagnosis was the same as that from the thoracoscopic biopsy. In these 6 cases, the same diagnosis was obtained only in those with idiopathic interstitial pneumonitis or diffuse panbronchitis. Thoracoscopic lung biopsy was safe and useful for diagnosis for diffuse infiltrative lung disease. PMID- 11197147 TI - Plasma beta-phenylethylamine in Parkinson's disease. AB - Plasma beta-phenylethylamine (PEA) levels were determined in 27 patients with Parkinson's disease (PD) in order to evaluate its relation with the severity or clinical course of PD. The plasma PEA concentrations in PD patients were significantly lower (mean +/- SD, 862 +/- 554 pg/ml) than those in the control group (1765 +/- 790 pg/ml) (p < 0.0001). The concentrations of PEA in plasma did not correlate with Hoen and Yahr stage. However, in serial measurements of the PEA of 5 patients in the progressive group of the clinical course of PD, the plasma PEA levels revealed a downward trend after one or two years. On the other hand, in 3 patients of non-progressive group, the plasma PEA remained at the same level. This study suggests that plasma PEA level might reflect nigrostriatal degeneration in patients with PD. PMID- 11197148 TI - Shedding of herpes simplex virus type 1 into tears and saliva in healthy Japanese adults. AB - It is well known that asymptomatic viral shedding is one of the forms of reactivation of herpes simplex virus type-1 (HSV-1). Although there have been some long-term investigations of viral shedding into tears and saliva in healthy subjects in the U.S.A, there have previously been no investigation study in Japan. Racial differences in the incidence of reactivation of HSV-1 have been pointed out, and it has been considered that reactivation is found less often among Japanese people than among Westerners. In the present study, we selected 10 healthy adults (7 males and 3 females) to isolate HSV-1 from tears and saliva 3 times a week over 6 months, and the results were compared with the results of other studies conducted in the U.S.A. It was found that the virus was isolated in 5 (3 males and 2 females) of 10 subjects and of the 5 subjects, the virus was isolated from saliva in 4 and from tears in 1. The number of specimens was 1,742 for tears and 871 for saliva with isolation of 1 and 4, respectively. The duration of shedding was only 1 day in all of the 5 subjects in whom the virus was isolated. The isolation frequency was significantly lower among Japanese people than among American people when our results were compared with the results of studies conducted in the U.S.A. It was clear that the reactivation rate was lower for Japanese people in terms of asymptomatic shedding. PMID- 11197149 TI - Effectiveness of an educational trial to encourage sufficient calcium intake in women college students. AB - An educational trial to encourage sufficient calcium (Ca) intake was conducted on women college students who entered the college for dietitian either in 1993 or in 1994. The trial's effectiveness was assessed by a prospective cohort study. Two hundred and fifteen 18- or 19-year-old students were assigned into two cohorts, i.e., a control cohort (CC) and an educated cohort (EC). Both groups received 3 surveys, i.e., at baseline, 1 week after, and 1 year after the Ca education, which was given only to the EC at baseline to encourage sufficient Ca intake. The amount of Ca taken by the CC did not significantly change in the 3 surveys. The EC took a significantly larger amount of Ca 1 week after and maintained relatively larger amount of Ca 1 year after the Ca education. These results suggest some effectiveness of Ca education on the women college students. PMID- 11197150 TI - Effect of facial affect stimuli on auditory and visual P300 in healthy subjects. AB - This study investigated whether or not P300 components are influenced by emotional affect such as sadness and pleasure in twenty healthy subjects and whether or not the P300 effects of facial affect stimuli are influenced by auditory and visual stimulus modalities. Written informed consent was taken from each subject before the study. Each subject was asked to stare at a simple picture of a facial expression (crying or smiling faces) during the auditory and visual oddball tasks. P300 amplitude and area were significantly larger when viewing a crying face (sadness) than a smiling face (pleasure) under both conditions with auditory and visual stimulus. P300 latency was significantly longer while viewing sadness than while viewing pleasure only with auditory stimuli. Reaction time was not changed by facial stimuli. Amplitude and area of P300 were significantly larger in women than men in their modalities, but the effects of facial affect on P300 amplitude and area in women were similar to those in men. These results suggest that amplitude and area of P300 with both modalities recorded while viewing sadness may induce larger attentional resource than pleasure. Gender was a less potent influence of facial expression on P300 parameters. The influence of facial emotion may be important to investigate the recognition processes of subjects. PMID- 11197151 TI - Comparison of the inpatients admitted during the recent 5 years (January 1994 December 1998) with those admitted during the previous 5 years (January 1989 December 1993): a clinico-statistical study. AB - As society ages, the composition of the diseases that occur within it changes accordingly. With that in mind, we examined the characteristics and trends in the recent inpatients and compared these recent inpatients with those of a previous report to identify the changes that accompany the aging of society. Subjects were 1,534 cases (men 56.9%, female 43.1%, average age 47.1 years) who were hospitalized at Kurume University Hospital for treatment during the 5-year period from January 1st, 1994 through December 31st, 1998. The ratio of inpatients over 65 years old was about 1.8 times higher than in the previous study, showing a clear trend toward an increased overall age of inpatients. As for the types of disease observed, the most common malignancies were epithelial tumor, followed by other benign tumors, as well as 76 cases which included diseases resembling tumor (epulis and exostosis etc.). A majority of the patients (55.6%) were directed to the Hospital by their dentist, a finding similar to that of the previous report. As for geographical distribution, 93.3% of the inpatients lived within 40 km of the center of Kurume City where our oral surgery is located, an increase of about 10% from the last report. In other words, our results showed a reduction in the sphere of treatment distribution. PMID- 11197152 TI - Profiles of herpes simplex virus type 1 antibodies in primary herpetic infections of the maxillofacial regions. AB - Changes in the aspects of primary infection of herpes simplex virus type 1 in the maxillofacial region have been observed due to the increase in the number of adult cases. To elucidate the possibility of serologic diagnosis in primary infectious patients and the influence of virucide on antibody production, we evaluated changes in serum antibodies (neutralizing antibody, IgM, and IgG antibody) in pair serum in 35 primary infectious patients using a micro-plate method and ELISA. At the first examination, 31 (89%) of 35 patients did not have neutralizing antibodies, and 23 of the 31 patients showed significant increases of neutralizing antibody titer more than four times at the second examination. Three of the 4 patients that had neutralizing antibodies showed significant increases at the second examination; therefore, 26 (74.3%) of the 35 patients could be diagnosed as having primary infection only by neutralizing antibodies. Regarding 9 patients who did not show significant increases in neutralizing antibodies, 5 of the 9 patients showed increases in IgG antibody titer more than two times at the second examination, and at the first examination, IgM antibody titer in 3 of the remaining 4 patients was more than 0.2 that is the cut-off value; therefore, it was possible to diagnose the 8 patients as having primary infection. We evaluated the influence of the use of virucide, gender, age, period between onset and the first examination, and period between onset and the second blood collection on antibody production; however, there were no differences observed except that significant increases in antibody were observed in 4 children aged below 10 years, although they used virucide. These results revealed that it was not possible to serologically diagnose whether there was primary or recurrent infection only by neutralizing antibody titer. PMID- 11197153 TI - Histomorphological investigation regarding to malignant transformation of pleomorphic adenoma (so-called malignant mixed tumor) of the salivary gland origin: special reference to carcinosarcoma. AB - Pleomorphic adenoma is the best-recognized tumor among those of salivary gland origin that also has the highest incidence. However, it is not uncommon for it to become malignant, and it has been noted that the frequency of malignancy increases as a result of the tumor persisting without being treated following the onset of adenoma. Carcinomatous components demonstrate various histological appearances, and in particular, there have been sporadic reports of carcinosarcoma in which malignant findings are not only observed in epithelial components, but in mesenchymal components as well. We conducted a histopathological study on cases of malignant-transformed pleomorphic adenoma, namely so-called malignant mixed tumor observed in our department. The subject cases consisted of a total of 19 cases registered in the diagnostic files of our department and included 12 males and 7 females. Age ranged from 46 to 87 (average 67.7) years old. The sites of occurrence consisted of the parotid gland in 17 cases, and palatal and buccal minor salivary glands in one case each. Histological types consisted of 7 cases of adenocarcinoma not otherwise specified, 3 cases of squamous cell carcinoma, 3 cases of salivary duct carcinoma, and one case each of polymorphous low-grade adenocarcinoma and epithelial-myoepithelial carcinoma, while the remaining were 2 cases of sarcomatoid carcinoma and 2 carcinosarcoma. We described herein their histological characteristics, discussed diagnostic problems in various instants in which each phenotype on this setting, and reviewed the literature, especially as to carcinosarcoma in contrast with those derived from other organs. PMID- 11197154 TI - Advanced gastric cancer with liver metastasis effectively treated by intra hepatic arterial infusion of 5-FU, MMC and peroral administration of 5-FU: a case report. AB - We have experienced a case of advanced gastric cancer with liver metastasis effectively treated by intra-hepatic arterial infusion of 5-fluorouracil (5-FU), mitomycin C (MMC) and peroral administration of 5-FU. The patient was a 48-year old male diagnosed as having advanced gastric cancer with multiple liver metastasis in the bilateral lobes of the liver. This patient was treated by intra hepatic arterial infusion of 5-FU (250 mg/2 days x 8 doses), MMC (20 mg x 1 dose, 6 mg/2 weeks x 6 doses) and peroral administration of 5-FU (200 mg/day). At 14 weeks later, a CT revealed that the metastatic liver tumors had disappeared. However, at 7 months after the therapy, the patient eventually died of liver and brain metastasis. These results suggested that intra-hepatic arterial infusion of 5-FU and MMC was an effective therapy for metastatic tumors in the liver, but we need to perform intra-hepatic arterial infusion using a new prolonged regimen to treat the liver metastasis. PMID- 11197155 TI - Multiple carcinoids in the stomach with hypergastrinemia and type A gastritis: a case report. AB - We have experienced a case of the stomach with hypergastrinemia and type A gastritis with multiple carcinoids in a 37-year-old woman. An upper gastrointestinal series revealed multiple minute polyps in the upper body of the stomach. All polyps were diagnosed as carcinoid using endoscopic biopsies. She had neither symptom or signs of typical carcinoid disease. The serum gastrin level was as high as 725 pg/ml. Total gastrectomy was performed, and the diagnosis of multiple gastric carcinoids (sm, no) with type A gastritis was histologically confirmed. After the operation, the serum gastrin level returned to normal, and the patient has been doing well and is disease-free to date at 7 years after the operation. This case suggested that multiple gastric carcinoid lesions may be precipitated by chronic atrophic gastritis accompanying hypergastrinemia. In the treatment of multiple gastric carcinoids with type A gastritis, total gastrectomy with lymph node dissection should be standard operative procedure, in order to resect the fundic gland area completely which could be the origin of carcinoids and endocrine cell micronest. PMID- 11197156 TI - Separation of N2-ethyl-2'-deoxyguanosine-5'-monophosphate and four native deoxyribonucleoside monophosphates using capillary zone electrophoresis with polyethylene glycol as buffer additive. AB - We investigated the separation of five deoxyribonucleoside monophosphates: 2' deoxyguanosine-5'-monophosphate (dGMP), 2'-deoxyadenosine-5'-monophosphate (dAMP), 2'-deoxycytosine-5'-monophosphate (dCMP), 2'-deoxythymidine-5' monophosphate (dTMP) and a dGMP adduct possessing N2-ethyl-guanine, which has been noted in relation to mutagenesis of alcohol, using capillary zone electrophoresis (CZE). The concentration of polyethylene glycol (PEG) as a modifier and the pH of the running solutions can efficiently control the observed separation. Interaction of PEG with analytes was quantitatively evaluated. PEG worked effectively as a hydrophobic selector in these separations. The values of pKa of the acidic-NH-groups in the base moieties of dGMP, dTMP, and the dGMP adduct are close to that of boric acid used as buffer of the running solutions. The control of their charge was facilitated, enabling improved separations. A more sufficient and fast separation was achieved by both optimization of pH of the running solutions and PEG concentration compared with that obtained by pH control alone. On-line concentration using a stacking method followed by the PEG assisted CZE was briefly studied. PMID- 11197157 TI - Evaluation of norbornene- beta-cyclodextrin-based monomers and oligomers as chiral selectors by means of nonaqueous capillary electrophoresis. AB - Norbornen-5-yl carboxylic acid and norbornen-5-ylmethylsilyl ether-based beta cyclodextrins (beta-CDs) containing up to three norbornene ester and up to five norbornene silyl ether units have been prepared from beta-CD and norbornen-5 carboxylic chloride and norbornen-5-ylmethyldichlorosilane, respectively. Oligomers (n = 2-4) were prepared therefrom using ring-opening metathesis polymerization (ROMP). Monomeric and oligomeric substituted beta-CDs were evaluated as chiral selectors in nonaqueous capillary zone electrophoresis using 35 mM sodium bicarbonate in N-methylformamide (NMF) as background electrolyte. Both monomeric and oligomeric norbornene ester- and norbornene silyl ether-type selectors showed good enantioresolution for dansylated (DNS-) amino acids using concentrations of the chiral selector of up to 4% w/v. A significant improvement in resolution was observed upon the introduction of up to five norbornene silyl ether units into a beta-CD molecule, whereas higher degrees of substitution with norbornen-5-yl-carboxyl groups lead to a reduction in enantioresolution of DNS amino acids. Thus, pentakis(norbornen-5-ylmethylhydroxysiloxyl)-beta-CD turned out to be superior to mono(norbornen-5-ylmethylhydroxysiloxyl)-beta-CD in terms of enantioresolution. Moreover, norbornene silyl ether-type selectors were found to be more efficient than norbornene ester-type selectors. Finally, oligomeric selectors were found to possess superior or at least comparable enantioselectivity in the separation of DNS-amino acids compared to the parent monomers. A maximum in enantioresolution was obtained with oligo(pentakis(norbornen-5-ylmethylhydroxysiloxyl)beta-CD). PMID- 11197158 TI - Comparison of binding of tetraphenylborate and tetraphenylphosphonium ions to cyclodextrins studied by capillary electrophoresis. AB - Binding constants for tetraphenylborate and tetraphenylphosphonium ions (Ph4B- and Ph4P+) to cyclodextrins (CDs) to give 1:1 host-guest complexes have been measured using capillary electrophoresis. Mobilities of the ions as a function of gamma-CD concentration give binding constants, K, of 1.08 x 10(5) M-1 for Ph4B- and 0.6 x 10(1) M-1 for Ph4P+. This dramatic difference of four orders of magnitude in binding constants is not seen with beta-CD (K = 7.7 x 10(1) M-1 for Ph4B- and 3.7 x 10(1) M-1 for Ph4P+) or dimethyl (DM)-beta-CD (K = 46 x 10(1) M-1 for Ph4B-1 and 7.7 x 10(1) M-1 for Ph4P+). The crystal and hydrodynamic radii of the ions, the latter calculated from their absolute mobilities, indicate that Ph4B- is smaller than the gamma-CD cavity, whereas Ph4P+ is approximately the gamma-CD cavity size. Results suggest that Ph4B- fits exactly into a gamma-CD cavity, with hydrophobic contacts involving several of the phenyl rings, whereas Ph4P+ is too large to enable these multiple contacts to be made. When only a single phenyl ring can fit into the CD cavity, binding strengths are in the order DM-beta-CD > beta-CD > gamma-CD and Ph4B- > Ph4P+. Measurement of electrophoretic mobilities of the complexes shows that their hydrodynamic radii are in the order gamma-CD < beta-CD approximately DM-beta-CD for Ph4B- and gamma-CD > beta-CD approximately DM-beta-CD for Ph4P+. PMID- 11197159 TI - Expression of alpha-amylase gene in rat liver: liver-specific amylase has a high affinity to glycogen. AB - The reactivity of rat liver alpha-amylases with maltotriose (G3), maltopentose (G5) and glycogen has been investigated. Liver amylases were found to be glycosylated and to have a molecular mass of 50 kDa by Western blotting using an anti-human salivary amylase antibody. The glycosylated liver amylases were found to be capable of G3- and G5-hydrolysis and of glucose formation, as demonstrated by thin-layer chromatography. When the amylase preparation was exposed to different concentrations of glycogen and run on a cellulose acetate membrane, the mobilities of rat liver amylases significantly decreased with tailing directly from the point of origin. In contrast, rat salivary amylases were not so much. These results indicate that rat liver amylases have a strong affinity to glycogen. We confirmed the expression of liver-specific amylases in rat liver by reverse transcriptional-polymerase chain reaction (RT-PCR); PCR products showed one band of an expected size of 474 bp using primers tested in the present study. A partial nucleotide sequence was then determined. When compared with the gene of mouse liver amylase, the substitution of 26 bases out of 434 bases was elucidated. The present data demonstrate the presence of liver-specific amylases in rats. PMID- 11197160 TI - Chiral analysis of baclofen by alpha-cyclodextrin-modified capillary electrophoresis and laser-induced fluorescence detection. AB - An enantioselective method for baclofen (4-amino-3-p-chlorophenylbutyric acid) based on capillary electrophoresis (CE) separation and laser-induced fluorescence (LIF) detection has been developed. Naphthalene-2,3-dicarboxaldehyde (NDA) was used for precolumn derivatization of the nonfluorescent drug. alpha-Cyclodextrin (alpha-CD) was included in the buffer as a chiral selector for the separation of NDA-labeled S-(+)- and R-(-)-baclofen. Optimal resolution and detection were obtained with an electrophoretic buffer of 50 mM sodium borate (pH 9.5) containing 7 mM alpha-CD and a He-Cd laser (lambda ex = 442 nm, lambda em = 500 nm). Combined with a simple cleanup procedure, this method can be applied to the analysis of baclofen enantiomers in human plasma. The relative standard deviation (RSD) values on peak areas of a plasma sample containing 1.0 microM racemic baclofen were 6.4 and 4.9% (n = 8) for the S-(+)- and R-(-)-enantiomer, respectively. The RSD value on migration times of both enantiomers was 0.5% (n = 8). Calibration graphs for S-(+)- and R-(-)-baclofen in plasma showed a good linearity (r > or = 0.999) in the concentration range of 0.1-2.0 microM. The limit of detection of baclofen in plasma was about 10 ng/mL. PMID- 11197161 TI - Monitoring human serum transferrin by capillary zone electrophoresis with end column amperometric detection. AB - Capillary zone electrophoresis was employed for the determination of human serum transferrin using end-column amperometric detection with a carbon fiber microelectrode at a constant potential of 1.9 V vs. saturated calomel electrode (SCE). The optimum conditions of separation and detection are 7.5 x 10(-4) mol/L Tris-3.44 x 10(-4) mol/L HCl for the buffer solution, 20 kV for the separation voltage, 5 kV and 10 s for the injection voltage and the injection time, respectively. The limit of detection is 6.7 x 10(-8) mol/L or 440 amol (S/N = 2). The relative standard deviations are 0.67% for the migration time and 1.5% for the electrophoretic peak current. The method was applied to the determination of transferrin in human serum. The recovery is between 93-104%. PMID- 11197162 TI - Simultaneous determination of doxorubicin, daunorubicin, and idarubicin by capillary electrophoresis with laser-induced fluorescence detection. AB - The separation and simultaneous determination of doxorubicin, daunorubicin and idarubicin was investigated using capillary electrophoresis with laser-induced fluorescence detection. Because the three anthracycline antibiotics were similar in structure and mass, careful manipulation of the electroosmotic flow and electrophoretic mobilities was required. A buffer consisting of 100 mM borate, adjusted to pH 9.5, containing 30% acetonitrile was found to provide a very efficient and stable electrophoretic system for the analysis of the three anthracyclines. The method was applied to the determination of three anthracyclines in serum samples. Responses were linear in the range of 10-500 ng.mL-1 and the detection limits were lower than 0.9 ng.mL-1. PMID- 11197163 TI - Separation of cold medicine ingredients by capillary electrophoresis. AB - This study demonstrates the separation of cold medicine ingredients (e.g., phenylpropanolamine, dextromethorphan, chlorpheniramine maleate, and paracetamol) by capillary zone electrophoresis and micellar electrokinetic chromatography. Factors affecting their separations were the buffer pH and the concentrations of buffer, surfactant and organic modifiers. Optimum results were obtained with a 10 mM sodium dihydrogen-phosphate-sodium tetraborate buffer containing 50 mM sodium dodecyl sulfate (SDS) and 5% methanol (MeOH), pH 9.0. The carrier electrolyte gave a baseline separation of phenylpropanolamine, dextromethorphan, chlorpheniramine maleate, and paracetamol with a resolution of 1.2, and the total migration time was 11.38 min. PMID- 11197164 TI - Determination of nucleosides in natural Cordyceps sinensis and cultured Cordyceps mycelia by capillary electrophoresis. AB - Cordyceps sinensis is a well-known traditional Chinese medicine, and some of the active components are nucleosides. The analysis of nucleosides in Cordyceps material has been performed by reversed-phase high-performance liquid chromatography (HPLC) with gradient elution or by spectrometry. Here, we have explored the possibility of using capillary electrophoresis to determine the content of three major nucleosides (adenosine, guanosine and uridine) in Cordyceps. Capillary electrophoresis needs no gradients, and it provides a better separation due to its higher efficiency. In order to optimize the resolution, the separation of adenosine, guanosine and uridine was determined in Cordyceps with respect to the variation of buffer concentration, pH, temperature, and voltage. By using the calibrated electrophoresis system, the separation was achieved for the three nucleosides in less than 10 min with a background electrolyte consisting of 0.2 M boric acid-sodium hydroxide buffer, pH 8.5. The nucleoside contents of various types of natural Cordyceps and cultured Cordyceps mycelia were determined and compared. There was a great variation of nucleoside content in different sources of Cordyceps; the cultured Cordyceps mycelia, however, contains a much higher concentration than the natural Cordyceps. PMID- 11197165 TI - Determination of synthesized alpha-vitamin E by micellar electrokinetic chromatography. AB - We developed a micellar electrokinetic chromatography method (MEKC) for the direct determination of the content of synthesized alpha-vitamin E. It was found that under the optimum separation conditions 7 mM borate + 14 mM phosphate + 15 mM sodium dodecyl sulfate (SDS) + 10 mM sodium cholate (NaCh) + 8% acetonitrile (pH 9.2) with UV detection wavelength at 214 nm, 16 kV constant voltage, and 26 degrees C constant temperature, alpha-vitamin E and its isomers can be baseline separated and alpha-vitamin E was quantitatively analyzed. In addition, the sample recovery, the limit of detection and the repeatability of the method were investigated. The influence of various parameters on the separation such as SDS concentration, NaCh concentration, buffer pH and acetonitrile percentage were also discussed. PMID- 11197166 TI - Identification of a phosphoprotein that is downregulated in immortalized human fibroblasts. AB - Many lines of evidence indicate that the immortalization step is critical for the neoplastic transformation of normal human cells. Once normal human cells have been immortalized, they are relatively easily transformed into neoplastic cells. In order to understand these phenomena, patterns of protein phosphorylation in proliferating normal human fibroblast cell strains and their immortalized cell lines were compared by using two-dimensional polyacrylamide gel electrophoresis. It was found that the expression and phosphorylation levels of the human heat shock protein 27 (HSP27) were predominantly downregulated in the immortalized cells compared with those in their normal counterparts. In the normal cells, HSP27 expression and phosphorylation were markedly increased by physiological and nonphysiological stresses, such as serum addition, treatment with a carcinogenic agent like 4-nitroquinoline-1-oxide, and a high osmotic pressure. This may be a normal defense against acute changes of cellular environment and cytotoxic effects. However, these stresses had no effects on the expression and phosphorylation of HSP27 in the immortalized cells. These results suggest that an abnormal regulation of HSP27 expression and phosphorylation may be one of the reasons for easy neoplastic transformation of the immortalized cells by the treatment with carcinogenic agents. PMID- 11197167 TI - Nondenaturing two-dimensional electrophoretic analysis of loop-sheet polymerization of serpin, squamous cell carcinoma antigen-2. AB - Two homologous serine proteinase inhibitors (serpins), squamous cell carcinoma (SCC) antigen-1 and -2 were separated by nondenaturing two-dimensional electrophoresis combined with immunostaining to acquire further information on these proteins under physiological conditions. Polymers of SCC antigen-2 were detected in cytosolic extracts prepared from tumor tissues. The polymer formation of SCC antigen-2 was apparently decreased and the SCC antigen-2-synthetic peptide binary complexes were newly formed by the addition of synthetic peptide with sequences corresponding to residues from P14 to P2 in the reactive center loop of SCC antigen-2. On the other hand, the incubation with synthetic peptides having the sequence of the reactive center loop of SCC antigen-1 or antithrombin had no effect on polymerization of SCC antigen-2. These data suggest that the polymerization of SCC antigen-2 may occur spontaneously in vivo by the loop-sheet mechanism of serpin. PMID- 11197168 TI - Reduced proteolysis of surfactant protein A and changes of the bronchoalveolar lavage fluid proteome by inhaled alpha 1-protease inhibitor in cystic fibrosis. AB - In cystic fibrosis (CF), the chronic neutrophilic inflammation of the airways results in proteolytic degradation of lung tissue early in the course of the disease. Inhalation of alpha 1-protease inhibitor (alpha 1-PI) may restore the protease-antiprotease imbalance and thus lead to less tissue damage. To monitor its impacts on bronchoalveolar lavage (BAL) fluid protein pattern (proteome) and on surfactant protein A (SP-A), eight young adults with CF inhaled 100 mg of alpha 1-PI twice daily over eight weeks. BAL fluids were obtained before and after inhalation. Total protein, the number and amount of proteins with a molecular mass < 20 kDa were reduced compared to pretreatment values. Degradation products of SP-A were shown by immunoblotting, being reduced after alpha 1-PI treatment. This pilot study demonstrates that inhalation of alpha 1-PI is associated with biochemical changes consistent with reduced proteolysis. The display of the BAL proteome by two-dimensional electrophoresis may be helpful to quantify the overall molecular changes associated with proteolytic or other lung injuries and offers the possibility to monitor directly therapeutic interventions. PMID- 11197169 TI - Changes of voltage-dependent anion-selective channel proteins VDAC1 and VDAC2 brain levels in patients with Alzheimer's disease and Down syndrome. AB - Voltage-dependent anion-selective channel proteins (VDACs) are pore-forming proteins found in the other mitochondrial membrane of all eukaryotes and in brain postsynaptic membranes. VDACs regulate anion fluxes of a series of metabolites including ATP, thus regulating mitochondrial metabolic functions. We determined protein levels of VDACs in individual post-mortem brain regions of patients with Down Syndrome (DS) and Alzheimer's disease (AD) using two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization-mass spectroscopy (MALDI-MS). VDAC1 (SWISS-PROT accession number P21796) and VDAC2 (P45880) were unambiguously identified and quantified, but VDAC3 was not found. The spots representing VDAC1 were separated with different p/s (p/7.5, 8.5, and 10.0) probably caused by post-translational modifications as, e.g., phosphorylation. In DS cerebellum, total VDAC1 protein was elevated significantly whereas VDAC2 did not show any significant alterations. In AD brains, VDAC1 p/10.0 was significantly reduced in temporal, frontal, and occipital cortex with the p/7.5 form elevated in occipital cortex. Total VDAC1 was significantly decreased in frontal cortex and thalamus. VDAC2 was significantly elevated in temporal cortex only. The biological meaning of our results may be derangement of voltage-dependent anion-selective channel function and reflecting impaired glucose, energy, and intermediary metabolism as well as apoptotic mechanisms. PMID- 11197170 TI - Contribution of blotting techniques to the study of rapeseeds (Brassica napus L.) lipases. AB - A recent advance in the study of plant lipases involving immunological techniques is presented. In an attempt to characterize lipases of cotyledons from germinating rapeseed seedlings and to investigate an eventual cross-reactivity with animal lipases, we have prepared anti-porcine pancreatic lipase antibodies raised in rabbit. It is shown by enzyme-linked immunosorbent assay and dot blotting that these antibodies react with lipases in the rapeseed crude extract and in the different cellular fractions obtained by differential centrifugation. Preincubation of the antiserum with the rapeseed crude extract affects the amount of antibodies binding to the porcine pancreatic lipase. We demonstrate immunochemical cross-reactivity between rapeseed and porcine pancreatic lipase. Using the immunoblotting procedure, it is found that antibodies bind specifically to a single polypeptide with a molecular mass of about 55 kDa. Rapeseed lipase activity decreased after immunoprecipitation suggesting that antibodies were bound to some catalytic site residues. We conclude from the data obtained in this study that the two different lipase species present close similarities in amino acid sequence and antigen characteristics. PMID- 11197171 TI - Controversies over heteroplasmy. PMID- 11197172 TI - Hundredfold productivity of genome analysis by introduction of microtemperature gradient gel electrophoresis. AB - Genome profiling, which employs temperature-gradient gel electrophoresis (TGGE) for DNA analysis, has recently been developed in identifying species by genotype. However, the performance of this technology like the general applications of TGGE was, though highly informative, limited in its ability due to methodological reasons. This study demonstrates that minimization of the gel for TGGE, to around one-tenth of its conventional size (approximately 2 cm), can be successfully introduced, resulting in a hundredfold higher performance (total evaluation of time, cost, and degree of parallel operations) than that of the conventional. Reproducibility was evaluated from the measures of the pattern similarity scores (PaSS) between band patterns (genome profiles) obtained with the conventional TGGE, and that with micro-TGGE (microTGGE) developed here, after extracting a set of featuring points from genome profiles. Size minimization, which leads to the reduction of the amount of samples required (cost-saving), is another great advantage, enhancing the employment of multicolor fluorescence technology. Since the further development of microbe-related fields such as epidemiology and microbial ecology inevitably require knowledge based on the identification of a great number of species and strains, microbe-related fields will receive the most optimal benefits from the technological improvements attained here. PMID- 11197173 TI - Multiple voltage-gradient gel electrophoresis system. AB - A new device, based on the principle of voltage-gradient gel electrophoresis, was developed in order to enhance differentiation of the distance across the range of molecular masses in the electrophoretic fractionation of nucleic acids in an agarose matrix. The apparatus has a series of modular parallel plates, placed slantwise to allow reiteration of the voltage gradient effect along the gel. This subjects DNA fragments of variable length to differential runnings according to their original position in the gel. Both the number of slantwise plates and the distance between them can be changed to modify operating performance. Our system allows better fractionations as compared to conventional electrophoresis, since it forms gel areas in which distancing between the ranges of molecular masses is enhanced. PMID- 11197174 TI - Heparan sulfate, heparin, and heparinase activity detection on polyacrylamide gel electrophoresis using the fluorochrome tris(2,2'-bipyridine) ruthenium (II). AB - The paper shows the ability of the fluorochrome tris(2,2'-bipyridine) ruthenium (II) (Rubipy) to detect heparan sulfate, heparin, and heparinase activity of M3 murine mammary adenocarcinoma cells as well as bacterial heparinases I, II, and III in native polyacrylamide gel electrophoresis (PAGE). The technique is based on the electrophoretic mobility of high molecular weight heparins and subsequent staining with Rubipy (50 micrograms/mL). The minimum content of heparin detected by fluorescence in a UV transilluminator was 25-50 ng. The number of Rubipy molecules bound to heparin, determined in relationship to the number of disaccharide units (DU), showed that two to six heparin disaccharide units are bound by each fluorochrome molecule. Scatchard plot analysis showed one Rubipy binding site (Kd = (8.56 +/- 2.97) x 10(-5) M). Heparinase activity was determined by densitometric analysis of the fluorescence intensity of the heparin containing band of the gel. While heparinase I (EC 4.2.2.7.) degraded heparin and, to a lower degree, partially N-desulfated N-acetylated heparin (N-des N-Ac), heparinase II (no EC number) could efficiently degrade heparan sulfate (HS) and partially N-des N-Ac heparin. Finally, heparinase III (EC 4.2.2.8.) degraded HS almost exclusively. Only heparin and N-des N-Ac heparin were substrates for M3 tumor cell heparinases. We describe a qualitative, sensitive and simple method to detect heparinase activity and determine its substrate specificity using Rubipy fluorescence with heparin and heparan sulfate in multiple biological samples tested in parallel. PMID- 11197175 TI - An approach to the sensitivity of temperature-gradient gel electrophoresis in the detection of clonally expanded T-cells in cutaneous T-cell lymphoma. AB - Detection of T-cell clonality by polymerase chain reaction (PCR) and high resolution electrophoresis facilitates differentiation of early stages of cutaneous T-cell lymphoma (CTCL) from benign T-cell-rich dermatoses. However, data regarding the sensitivity of the various electrophoresis techniques differ remarkably. In the present study, the capacity of heteroduplex (HD)-loaded temperature-gradient gel electrophoresis (TGGE) to detect clonally expanded T cells was assessed systematically and modifications to the procedure were defined. Using our standard protocol, HD-TGGE detected clonal T-cell receptor (TCR)-gamma PCR products, generated from the Jurkat cell line, down to a total of 2 ng/microL (14 ng) DNA. However, slowly migrating single strands of the clonal PCR product reduced the amount of the clonality indicating homoduplices. To overcome this single-strand formation, thus decreasing the detection limit, the urea concentration in the gel and the temperature ramp for the HD-formation were altered, as well as the temperature gradient in the gel. Application of the modified protocol resulted in a tenfold lower detection limit of 0.15 ng/microL (1.05 ng) DNA in the clonal band. The sensitivity of the adapted HD-TGGE was investigated by dilution experiments using the well established T-cell lines Jurkat, Molt-4, MyLa and SeAx. By these approaches clonal PCR products diluted in nonclonal PCR products were detectable down to concentrations of 5-10%. Comparably, in the case of mixtures of clonal in nonclonal DNA the detection limit reached 5-10% clonal DNA. However, by dilution of clonal cells in nonclonal peripheral blood mononuclear cells, which corresponds to in vivo conditions, a lower detection limit of approximately 1-5% was observed. PMID- 11197176 TI - Electric light scattering from single-stranded DNA in linear polyacrylamide solutions. AB - The electric light scattering (ELS) of ssDNA (calf thymus, 10 kbp, 55 micrograms/mL) in denaturing polyacrylamide (PAA) solutions was studied as a function of applied sinusoidal electric field and polymer concentration. Electric fields of strengths up to 300 V/cm and of frequencies between 100 and 5000 Hz were applied. It was found that the ELS effect increases with the field strength and decreases at high frequencies. The dependence of the ELS effect of ssDNA on polymer concentration passes through a maximum at 1% PAA. The relaxation times of decay of the ELS effect increase with increasing polymer concentrations. It was demonstrated that ELS is a useful method for investigation of ssDNA behavior in the course of pulse-field electrophoresis in polymer solutions. PMID- 11197177 TI - Deficient brain snRNP70K in patients with Down syndrome. AB - The small nuclear ribonucleoprotein 70K (snRNP 70K; U1-70 kDa) is an integral part of the spliceosome, a large RNA-protein complex catalyzing the removal of introns from nuclear pre-mRNA. snRNP is one of the best-studied essential subunits of snRNPs, is highly conserved and its inactivation was shown to result in complete inhibition of splicing. Applying subtractive hybridization, we found a sequence with 100% identity to snRNP absent in fetal Down syndrome (DS) brain. This observation made us determine snRNP-mRNA steady-state levels and protein levels in brains of adult patients with DS. snRNP-mRNA and protein levels of five individual brain regions of DS and controls each, were determined by blotting techniques. snRNP-mRNA steady state levels were significantly decreased in DS brain. Performing Western blots with monoclonal and human antibodies, snRNP protein levels were decreased in several regions of DS brain, although one monoclonal antibody did not reveal different snRNP-immunoreactivity. Although decreased snRNP-protein could be explained by decreased mRNA-steady state levels, another underlying mechanism might be suggested: snRNP is one of the death substrates rapidly cleaved during apoptosis by interleukin-1-beta-converting enzyme-like (ICE) proteases, which was well-documented by several groups. As apoptosis is unrequivocally taking place in DS brain leading to permanent cell loses, decreased snRNP-protein levels may therefore reflect decreased synthesis and increased apoptosis-related proteolytic cleavage. PMID- 11197178 TI - A novel catalase mutation detected by polymerase chain reaction-single strand conformation polymorphism, nucleotide sequencing, and western blot analyses is responsible for the type C of Hungarian acatalasemia. AB - Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) screening was used for searching mutations of the catalase gene in two Hungarian hypocatalasemic families. A syndrome-causing mutation was found in a PCR product containing exon 7 and its boundaries. Nucleotide sequence analyses detected a G to T substitution at position 5 of intron 7. The effect of this splice site mutation was confirmed by Western blot analyses demonstrating a decreased catalase protein level in these patients. These findings represent a novel type (C) of catalase mutations in the Hungarian acatalasemic/hypocatalasemic patients. PMID- 11197179 TI - pH-independent large-volume sample stacking of positive or negative analytes in capillary electrophoresis. AB - In capillary electrophoresis, the short optical path length associated with on column UV detection imposes an inherent detection problem. Detection limits can be improved using sample stacking. Recently, large-volume sample stacking (LVSS) without polarity switching was demonstrated to improve detection limits of charged analytes by more than 100-fold. However, this technique requires suppression of the electroosmotic flow (EOF) during the run. This necessitates working at a low pH, which limits using pH to optimize selectivity. We demonstrate that LVSS can be performed at any buffer pH (4.0-10.0) if the zwitterionic surfactant Rewoteric AM CAS U is used to suppress the EOF. Sensitivity enhancements of up to 85-fold are achieved with migration time, corrected area, and peak height reproducibility of 0.8-1.6%, 1.3-3.7%, and 0.8 4.9%, respectively. Further, it is possible to stack either positively or negatively charged analytes using zwitterionic surfactants to suppress the EOF. PMID- 11197180 TI - pH-mediated field-amplified sample stacking of pharmaceutical cations in high ionic strength samples. AB - Capillary electrophoretic separation of samples of physiological origin typically have both poor resolution and efficiency due to destacking. We have previously reported a stacking method for concentration of catecholamines in artificial dialysate, or Ringer's solution. However, pH-mediated sample stacking of other cations has not been investigated. In this report, pH-mediated stacking has been extended to eletripan, dofetilide, doxazosin, sildenafil, UK-103,320, UK-202,581, and CP-122,288. These compounds were chosen without prior structural screening except that they were cationic at the pH of our background electrolyte (BGE). Capillary electrophoretic behavior of samples in BGE is compared with those of samples in Ringer's solution with and without pH-mediated acid stacking. Results indicate that the peak heights and efficiencies for acid-stacked samples are increased compared to the unstacked samples in Ringer's solution or BGE. For example, the peak efficiencies for 5 s injections of eletriptan in BGE and Ringer's solution are 138,000 and 72,000 plates, respectively. In contrast, a 10 s injection of eletriptan followed by acid injection for 16 s produces a peak with 246,000 plates. Evaluation of the stacking effect was performed by comparison of the peak height at similar peak efficiencies for samples in Ringer's solution with and without stacking. Using this method, pH-mediated acid stacking provides a 10- to 27-fold sensitivity enhancement for the seven cations. PMID- 11197181 TI - Discrimination between peak spreading in capillary zone electrophoresis of proteins due to interaction with the capillary wall and due to protein microheterogeneity. AB - Our study attempts to find an approach to distinguishing between the contribution to peak spreading in capillary zone electrophoresis (CZE) due to protein microheterogeneity and that due to interaction with the capillary wall, by analyzing correlations between observed peak spreading and peak asymmetry. The peak asymmetry was measured as ln[(tm-t1)/(t2-tm)] where tm, t1, and t2 are migration times at the mode of the peak and at the intersection of the peak width at half-height with the ascending and descending limbs, respectively. Two isoforms of recombinant green fluorescent protein (GFP-1 and GFP-2, 27 kDa molecular mass), glucose-6-phosphate dehydrogenase (GPD, 104 kDa), and the naturally fluorescent protein R-phycoerythrin (PHYCO, 240 kDa) were subjected to CZE in polyacrylamide-coated fused-silica capillaries of 50 and 100 microns diameters under varying conditions of protein concentration, field strength, and the initial zone length. Under conditions such that contributions to peak spreading from axial diffusion, thermal effects, and electrophoretic dispersion are negligible, the analysis of the interrelations between peak width and peak asymmetry was found to allow a conclusion as to the cause of peak spreading in CZE of protein. It appears that the peak width of GFP-2 originates mostly in protein microheterogeneity while that of GFP-1 is due to protein-capillary wall interactions. For PHYCO, both microheterogeneity and protein-capillary wall interactions contribute to peak spreading. GPD exhibits relatively little microheterogeneity or interaction with capillary walls. Thus, its peak width appears to be mostly affected by an extracolumn source of spreading such as the initial zone length. PMID- 11197182 TI - Determination of ebrotidine metabolites in overlapping peaks from capillary zone electrophoresis using chemometric methods. AB - This paper illustrates the possibilities of chemometric methods in the resolution and quantification of various compounds in overlapping peaks from capillary electrophoresis. Ebrotidine and most of its metabolites were efficiently separated by capillary zone electrophoresis (CZE) in a fused-silica capillary. However, the procedure was not suitable for the physical separation of the three less ionizable metabolites, which comigrated and overlapped with the electroosmotic flow signal. Multivariate curve resolution based on an alternating least squares procedure was used for their mathematical resolution. For such a purpose, data obtained in the CZE system with a diode array detector, which consisted of UV spectra registered over time, were analyzed. The ebrotidine metabolites were successfully resolved and quantified in synthetic mixtures and urine samples. PMID- 11197183 TI - Quantitative and qualitative precision improvements by effective mobility-scale data transformation in capillary electrophoresis analysis. AB - By transforming the time-based x-axis of electropherograms in capillary zone electrophoresis (CZE) into the corresponding effective mobility-scale, we propose a simple and robust data representation for a better qualitative and quantitative capillary electrophoresis (CE) analysis. The time scale of the raw electrophoretic data (detection signal versus time) is transformed into an effective electrophoretic mobility scale (mu eff-scale) with account of the electroosmotic flow (EOF) peak or of an internal standard of known effective mobility. With the new scaling (detection signals versus effective mobility), the obtained electropherograms are more representative of the velocity-based electrophoretic separation and the comparison of complete electropherograms is directly possible. This is of importance when tracking peaks in real samples where alteration in EOF stability can occur or when comparing electrophoretic runs from different experimental setups (independence in column length and voltage). Beside the qualitative possibilities, a quantitative improvement is achieved in the mu eff-scale with significant better peak area reproducibility and equal to more precision in quantitative analysis than with the primary time scale integration. PMID- 11197184 TI - Molecular recognition by chiral cationic micellar and micelle-like aggregates in electrokinetic capillary chromatography. AB - We examined the enantiomer separation with micelles and a micelle-like polymer made with trimethylammonium-terminated surfactants all of whose hydrocarbon chains contain hydrogen bonding valinediamide moieties in electrokinetic chromatography (EKC). The surfactants used were 3-(N-dodecanoyl-L-valylamino) propyltrimethylammonium bromide (surfactant 1) and 6-(N-nonanoyl-L valylamino)hexyl-trimethylammonium bromide (surfactant 2); the micelle-like polymer was derived from 3-(N-10-undecenoyl-L-valyl)aminopropyltrimethylammonium bromide (surfactant 3). N-Acylamino acids and their isopropyl esters were separated with enantiomers with the same configuration as the chiral surfactant and which were retained to a greater extent than the counterparts in micelles. The micellar hydrophobic environment, in which amides function as hydrogen bonding sites with solutes, and ceased micellar kinetic association-dissociation with polymerization are discussed. PMID- 11197185 TI - Separation and identification of platinum adducts with DNA nucleotides by capillary zone electrophoresis and capillary zone electrophoresis coupled to mass spectrometry. AB - Platinum adducts are supposed to be the cytotoxic lesions in DNA after platinum containing anticancer therapy. Various adducts are formed upon interaction of platinum complexes with nucleotides, but contribution of individual adducts to antitumor activity and toxicity of platinum complexes still remains to be examined. A capillary zone electrophoresis (CZE) method is described that is suitable to separate individual platinum adducts. We investigated the formation of adducts following the reaction of cis-diamminedichloroplatinum (II) (cisplatin) with various DNA nucleotides. Baseline separation of unmodified and modified nucleotides (adducts) was achieved using uncoated fused-silica capillaries and basic separation buffers. In order to elucidate the observed peak pattern, a coupled CZE-electrospray ionization-mass spectrometry (ESI)-MS approach was applied. After incubation of mononucleotides with cisplatin, monochloro, monoaqua and bifunctional adduct species were detected. Consequently, the migration order of nucleotides and individual platinum adducts could be determined. Moreover, the time-dependent conversion from monochloro to monoaqua and subsequently to bifunctional adducts was monitored. In conclusion, individual platinum adducts were separated by CZE and identified by CZE-ESI-MS. Formation and conversion of distinct species were confirmed. Potential applications comprise studies of novel platinum complexes, investigations of platinum-adduct formation with DNA, and determination of platinum-DNA adducts in cells. PMID- 11197186 TI - Temporality, sequential iconography and linearity in figures: the impact of the discovery of division in infusoria. AB - The paper analyses the impact of the discovery of the division of infusoria on eighteenth century microscopical iconography. In Autumn 1765, when reproducing the antispontaneist experiments of Lazzaro Spallanzani, Horace-Benedict de Saussure (1740-1799) discovered a new method of generation of the animalcules of the infusions, namely their division. Drawing a dividing animalcule raised particular problems, notably the question of how to depict the time sequence of a microscopical creature. Although Saussure's journal of microscopical experiments remained unpublished, the discovery was soon diffused and acknowledged by the European naturalists who began to repeat the observations and quickly faced iconographic problems similar to those experienced by Saussure. Indeed, linearity, used to picture time, is a construction, and, notably for public images, scholars had to contend with the conventions of drawers and engravers. The analysis of microscopical iconographic material of the period 1740-1786 shows that during this period, certain naturalists invented new solutions for depicting time, but diffusion of their innovations was not immediate. Nevertheless, in regards to the illustration of microscopical creatures, it is between 1765 and 1776 that the use of linearity was established as a solution enabling an audience to read an iconographic time process as a text. PMID- 11197187 TI - A century of research into the cause of cancer: is the new oncogene paradigm revolutionary? AB - Contemporary oncological research is predominantly characterised by genetic explanations, a situation which may be briefly denoted as the oncogene paradigm. This essay discusses why the new paradigm was perceived so attractive that it could take over the whole field of oncology within a time-span of less than two decades. It is argued that the revolutionary character of the oncogene paradigm stems from the fact that it transcends a dichotomy which has kept experimental cancer research divided for more than three quarters of a century. This concerns the dichotomy between so-called exogenous and endogenous explanations of cancer causation. This essay mainly focuses on the role of the exogenous/endogenous dichotomy in the reception of research on oncogenic viruses, especially discussing the work of Nobel laureate Peyton Rous on cancer viruses at the Rockefeller Institute. Rous was severely criticised by James Ewing, director of the Memorial Hospital for Cancer and Allied Diseases in New York, who held the idea that the origin of cancer was based in the cell. The twentieth century controversy over oncogenic viruses is placed in the context of the intense discussion over causality in medicine during the first decades of the twentieth century in Germany. It is argued that the oncogene paradigm may be seen as revolutionary because it succeeded in uniting the exogenous and endogenous explanations of cancer in a single paradigm. PMID- 11197188 TI - The blood from Auschwitz and the silence of the scholars. AB - The Kaiser Wilhelm Institute for Anthropology, Human Genetics and Eugenics in Berlin-Dahlem was the centre of scientific racism in Nazi Germany. Its bad history culminated in a research project to analyse the molecular basis of racial differences in the susceptibility to various infectious diseases such as tuberculosis. Josef Mengele, a former postdoc of the director of the institute, Otmar von Verschuer, collected blood samples and other material in Auschwitz from families and twins of Jews and Gypsies. The blood samples were analysed by Gunther Hillmann in the Berlin laboratory of Nobel Prize winner Adolf Butenandt. Butenandt had just moved to Tubingen. The project was paid for by the Deutsche Forschungsgemeinschaft. Butenandt, Hillmann and von Verschuer made scientific careers in the Federal Republic. To the present day this past has not been acknowledged by the Max-Planck-Gesellschaft as part of its history. PMID- 11197189 TI - The legacy of a scientist and his historian. PMID- 11197190 TI - Adherence to health messages: a social psychological perspective. AB - Non-adherence to regimes recommended by health practitioners is prevalent in the health and safety area. Even the most effective of interventions does not tend to lead to substantial improvements in adherence. This paper reviews models from the health psychology sphere that predict which factors might lead people to practice health-enhancing behaviours. In terms of health messages, the paper evaluates the methods of persuasion found to be most successful. It provides an analysis of a successful intervention, in which a target audience was motivated to adopt a health-enhancing choice. The paper concludes by examining the principles that can be drawn from successful interventions, in terms of changing a target audience's health behaviours. The focus is on those that can be applied to situations in which a health practitioner hopes to convince the patient to adhere to a preventive regime. PMID- 11197191 TI - Patient compliance with oral hygiene regimens: a behavioural self-regulation analysis with implications for technology. AB - Achieving optimal oral health through preventive efforts is a hallmark of the dental profession. A primary goal of a preventively-oriented dental practice is to encourage patients to practice appropriate oral self-care behaviours. When patients are asked to follow an oral self-care regimen, they are being given a target or goal (for example, brush twice a day) and their task is to control or regulate their behaviour to achieve that objective. Unfortunately, patients often fail to meet the expectations set forth by the clinical recommendation. This review examines the problem of poor patient compliance with oral hygiene regimens by applying the general principles that govern the self-regulation of behaviour. The component parts of a behavioural self-regulation model are reviewed in the context of oral self-care. Research in the area of toothbrushing behaviour is reviewed and methods for providing patients with feedback about their degree of compliance are discussed. PMID- 11197192 TI - An intervention programme to establish regular toothbrushing: understanding parents' beliefs and motivating children. AB - AIMS/OBJECTIVES: To determine the benefit of twice daily toothbrushing on newly erupted first permanent molars. To investigate, through the Health Belief Model, how parents' beliefs influence the likelihood of their children brushing twice a day. To identify aspects of a toothbrushing intervention programme that can be used in general dental practice. DESIGN: Randomised controlled trial. SETTING: Schools in deprived communities in Scotland. PARTICIPANTS: 461, 5-year-old children. INTERVENTIONS/METHODS: Supervised toothbrushing on school-days with a 1,000 ppm chalk-based fluoride toothpaste for two years. A school and home-based incentive scheme including toothbrushing charts, 6-monthly dental examinations and parental questionnaires. MAIN OUTCOME MEASURES: Caries increment and twice daily toothbrushing. RESULTS: In the control group, children who brushed once a day or less had 64% more caries than those who brushed at least twice a day (P = 0.001). In the intervention group this difference in caries was reduced to 16% (P > 0.05). The most significant parental belief explaining variation in twice-daily brushing was whether parents feel strongly that there is time to check their child's toothbrushing (P = 0.0001). The odds of these parents reporting that their child brushes twice daily are nearly three times greater. 95% of parents felt that toothbrushing charts would be a good way for dentists in practice to encourage children to brush regularly. CONCLUSIONS: The benefit of twice daily toothbrushing on caries development in newly erupted first permanent molar teeth is around 50% compared to brushing once a day or less. Parents' beliefs do influence the likelihood of their children brushing twice a day. Key parts of the intervention programme can be used when children attend general dental practice and would be welcomed by parents. PMID- 11197193 TI - The relevance of behavioural sciences in dental practice. AB - The aim of this paper is to illustrate how knowledge from behavioural sciences is necessary and relevant in creating a successful dental practice, benefitting patients and dental professionals. There are many ways to create a successful dental practice, the products of which are the various treatments performed by dentists or dental hygienists for their patients. Advanced technologies and methods are constantly improving these treatments and thus the technical and managerial aspects of dentistry. However, the success of dental practice is not only dependent on the technique applied or the technical skills of dental professionals, but also on patients, their attitudes and behaviour and the interaction between dental professionals and patients. It is well known that the success of dental treatments (for example, periodontal, orthodontic or implants) depends on the patient's behaviour, which includes compliance with certain oral hygiene regimens or specific dental visiting patterns. The outcome of the treatment depends on both the dental professional's knowledge and skills and the patient's skills, objectives and expectations. Furthermore, dental professionals and patients should be satisfied with the treatment plan as well as the outcome. This paper argues that in order for this to happen dental professionals need additional knowledge and skills from fields outside traditional dental sciences. In order to treat patients successfully, dental professionals must understand and change or modify patient behaviour, and the knowledge necessary for this is provided by the behavioural sciences. PMID- 11197194 TI - Reasons for replacement of restorations in permanent teeth in general dental practice. AB - OBJECTIVE: The analysis of reasons for the replacement of 9,805 amalgam, composite, glass ionomer, resin modified glass ionomer and 'other' restorations in permanent teeth in general dental practice. DESIGN: The data were subdivided on the bases of age and gender of the patients, the types of restorations and the clinicians' gender, experience and practice setting. RESULTS: The clinical diagnosis of secondary caries was the main reason for replacement of all types of restorations studied, followed by fracture of restorations, especially bulk fracture, irrespective of patient's age. Bulk discoloration was the third most common reason for replacement of resin based materials in adults, but it rarely occurred in adolescents 18 years and younger. The reasons for replacement of restorations were not associated with the gender of the patients. Subgroupings based on the clinicians' gender showed that female clinicians diagnosed secondary caries more often than male clinicians. Otherwise, the reasons for replacements were similar for both genders of clinicians. Subdivision of restorations based on the years since graduation of the clinicians resulted in small groups. The youngest group of clinicians diagnosed relatively more secondary caries both for amalgam and composite restorations than the most experienced group. CONCLUSION: The clinical diagnosis secondary caries was the main reason for replacement of all types of restorations studied. PMID- 11197195 TI - Further evidence for the reliability and validity of the Modified Dental Anxiety Scale. AB - AIM: To gain further evidence of the psychometric properties of the Modified Dental Anxiety Scale. SETTING: Dental admission clinics. DESIGN: Consecutive sampling, cross-sectional survey. PARTICIPANTS: Patients (n = 800) in four cities (Belfast, Northern Ireland; Helsinki, Finland; Jyvaskyla, Finland and Dubai, UAE). METHODS: Questionnaire booklet handed to patients, attending clinics, for completion following an invitation by the researcher to be included in the study. MEASURES: Modified Dental Anxiety Scale (MDAS), together with further questions concerning dental attendance and nervousness about dental procedures. RESULTS: Overall 9.3 per cent of patients indicated high dental anxiety. MDAS showed high levels of internal consistency, and good construct validity. The relationship of dental anxiety with age was similar to previous reports and showed lowered anxiety levels in older patients. CONCLUSION: Data from three countries has supported the psychometric properties of this modified and brief dental anxiety scale. PMID- 11197196 TI - Workforce requirements for a primary oral health care system. AB - AIM: To present the case for a primary health care (PHC) approach for dental care in Vietnam, and thereby contribute to a better understanding of the oral health problems that exist in many developing countries. METHODS: Information was obtained in Vietnam through discussions with dental and medical authorities of provincial health offices, educational institutions, hospitals, health centres and schools and by collecting data from record books and reports. FINDINGS: Dentistry lacks a PHC strategy and consequently urgent oral care and oral disease prevention and control are not available for the majority of the population in Vietnam. The curriculum of dental students and dental auxiliaries is not adequately directed to the oral health needs of the population. The present number of dental personnel is too low. CONCLUSION: A basic oral health care package (BOHCP) advocated by the WHO which could be incorporated into primary health services at sub-district level and in the school dental service would be most suitable to meet the oral health needs of the population in Vietnam. The oral health education component of the BOHCP may have more impact when it is conducted in close collaboration with non-dental health personnel and lay persons. The curriculum of dental personnel should be adjusted to meet the requirements of their future tasks. Dental auxiliaries, provided they are well trained can carry out the BOHCP. Consequently, there is a large need for this type of dental personnel in Vietnam. PMID- 11197197 TI - Introducing the Significant Caries Index together with a proposal for a new global oral health goal for 12-year-olds. AB - AIM: To describe a new index, the 'Significant Caries Index' (SiC Index) with the intention of focusing attention on those individuals with the highest caries scores in each population. METHOD: Attention is drawn to the skewed distribution of dental caries within a given population, indicating that there are still large groups of individuals who have considerably more caries than the WHO/FDI target level of DMFT 3 by the year 2000. The index is calculated as follows: individuals are sorted according to their DMFT values. The one third of the population with the highest caries score is selected and the mean DMFT for this subgroup is calculated. This value constitutes the SiC Index. RESULTS: The SiC Index can be easily calculated and used as a measure for future oral health goals. CONCLUSION: The SiC Index should be less than 3 DMFT in the 12-year-olds in a given population and it is hoped that this global oral health goal is reached at the latest by the year 2015. PMID- 11197198 TI - Caries patterns and their relationship to infant feeding and socio-economic status in 2-4-year-old Chinese children. AB - AIMS: To describe the prevalence, severity and patterns of caries in 2-4-year-old children and to evaluate the association between caries experience of the children and their feeding patterns and socio-economic background in terms of mothers' education and family income. DESIGN: Cross-sectional survey. SETTING: Suburban area of Hanchuan in Hubei province, China. PARTICIPANTS: A sample of 426 children (250 boys and 176 girls). METHODS: Dental-examinations were undertaken in kindergartens using World Health Organization diagnostic criteria for dental caries. Mothers completed a short questionnaire. OUTCOME MEASURES: Prevalence of caries; rampant caries; caries in incisors; caries in incisors and/or canines and molars; mean number of decayed, missing and filled teeth/surfaces (dmft/s). RESULTS: 36% of the children had caries, 7% had rampant caries. The more extensive pattern of caries involving primary molars as well as incisors and/or canines was seen in 12% of children. Children who had been wholly bottle-fed had five times the risk of having rampant caries compared to children who were breast fed. CONCLUSIONS: The results indicated that infant feeding practice might be a key risk factor for the development of caries at an early age in this country as elsewhere. PMID- 11197199 TI - Professional education and practice arrangements: are there gender differences among paediatric dentists in Israel? AB - AIM: To assess gender differences in professional education, practice setting and working arrangements among dentists in Israel, who primarily treat children. SUBJECTS: All 112 participants in the meeting of the Israeli Society of Dentistry for Children that was held in February 1999. METHODS: A questionnaire completed during the meeting. RESULTS: Seventy participants (63 per cent) completed the questionnaire and returned it. There were 43 females and 27 males. Less than half of the population were specialists (40 per cent of the females, 48 per cent of the males). No significant differences were found in the educational background and working in academia between females and males. With regard to practice arrangement, males significantly reported more frequently working in two clinics or more, than females (P = 0.049), and working in clinics with general practitioners (GPs) and specialists in various fields in dentistry, while more women reported working with either GPs or specialists (P = 0.007). In all other variables, no significant gender differences were found. The results of our study show that paediatric dentistry in Israel appears as a branch of the profession which shows great sexual equality of opportunity. PMID- 11197200 TI - Oral health status and treatment needs of 35-44-year old adults in Lebanon. AB - OBJECTIVES: The purpose of this study was to assess the oral health status and treatment needs of a Lebanese adult population. DESIGN: An epidemiological survey of 401 Lebanese adults aged 35-44 years was carried out in 1996. It followed the WHO methodology in assessing the oral health status and treatment needs of adult populations. A structured questionnaire and a standardised oral health exam were used for the investigation. RESULTS: Showed that the Decayed, Missing and Filled Teeth (DMFT) index was 16.3 and that 1.5 per cent of the sample had a DMFT score of zero, whereas, 55 per cent had a score of less than 4. Of the 401 subjects, 24 per cent had at least one bridge and 16 per cent had a removable prosthesis. Compared to other neighbouring countries, Lebanon ranked the highest in the DMFT index and its separate components. Close to 60 per cent of the sample was in need of operative treatment, 31 per cent needed tooth extraction and 60 per cent were in need of a crown or a bridge. Significant variations were observed in the oral health status as well as treatment needs of the sample when examining gender, socio-economic status, and place of residence differences. CONCLUSION: This study can be used as a stepping stone in the direction of building the base of knowledge on oral health in Lebanon. The planning and implementation of any strategy for oral health status improvement is crucial, alongside the country's infrastructure development. PMID- 11197201 TI - In vitro evaluation of two adhesive systems used with compomer filling materials. AB - AIM: To evaluate and compare the in-vitro shear bond strength, microleakage and dentine-restorative interface of a self-etching/self-priming dentine bonding agent with a three-component dentine-bonding agent. METHOD: For shear bond strength (SBS) testing 30 non-carious human molars were used of which 15 were tested with Non-Rinse Conditioner (NRC)/Prime&Bond NT (PBNT) and Dyract AP and 15 were tested with Scotchbond Multi-Purpose Plus (SBMP) and F2000. For the microleakage evaluation cavity preparations were made on the facial surfaces of 30 non-carious human premolars of which 15 were restored with NRC and PBNT with Dyract AP and 15 were restored with SBMP and F2000. The dentine-restorative interface was examined through a confocal scanning laser microscope (CSLM). RESULTS: The mean SBS of PBNT and SBMP were 12.8 and 18.1 MPa, respectively. The microleakage scores showed NRC/PBNT leaked on the dentine side in 13 of the 15 specimens examined. On the enamel side two of the 15 specimens showed microleakage. With SBMP no microleakage was observed on either enamel or dentine sides. The CSLM images show clear resin tag and hybrid layer formation for both the materials examined although SBMP showed better and deeper penetration into the dentine with longer resin tags. SBMP showed resin tags measuring about 150 mm while the hybrid layer measured about 5 mm. The length of the resin tags as well as the thickness of the hybrid layer for PBNT were 20 mm Pounds and 2 mm Pounds, respectively. CONCLUSIONS: The acid-etch technique of SBMP produced higher bond strength and no microleakage when compared with the self-etching/self-priming 'non-rinse technique' of NRC with PBNT. Thus it can only be speculated that SBMP should be the superior in the clinical situation. PMID- 11197202 TI - Teaching of posterior composite restorations in Japanese dental schools. AB - AIM: This study was conducted to assess the teaching programmes for Class I and II composite restorations in Japanese dental schools to obtain an overview of what is being taught, the relative teaching volume, the criteria for the provision of posterior composite restorations and the placement techniques taught. DESIGN: Questionnaire forms mailed to the operative dentistry teaching departments in all 29 Japanese dental schools. RESULTS: The response rate was 93 per cent, with replies from 27 of the 29 dental schools. Twenty-five (93 per cent) responding schools taught the use of Class I and two schools stated that they did not teach the use of posterior composite restorations. One of the two schools had no plan to teach posterior composites within the next five years. The other school did not answer this question. Most schools anticipated that the proportion of teaching time devoted to posterior composite restorations would increase within the next five years. Diversities and similarities between teaching programmes were noted between Japanese, North American and European dental schools, the Japanese programmes being closer to those in Europe than those in North America. CONCLUSION: The diversities in the teaching of posterior composite restorations in Japanese dental schools are as great as in other parts of the world. Such diversities must affect the overall quality of restorations in general practice. PMID- 11197203 TI - Interleukin-8: an expanding universe beyond neutrophil chemotaxis and activation. AB - Since the discovery 13 years ago of interleukin (IL)-8 as a potent neutrophil chemotactic factor, accumulating evidence has established it as a crucial mediator in neutrophil-dependent acute inflammation. Numerous observations have demonstrated that various types of cells can produce a large amount of IL-8, either in response to various stimuli or constitutively, after malignant transformation. Recent studies of IL-8-mediated signaling have revealed that IL-8 activates a wide range of signaling molecules in a coordinate manner. IL-8 has been proven to have diverse actions on various types of leukocytic and nonleukocytic cells besides neutrophils. The author reviews recent progress in IL 8 signal transduction and biological actions on nonneutrophilic leukocytes, including T lymphocytes, monocytes, and hematopoietic progenitor cells. Potential involvement of IL-8 in viral infections and tumor progression is also discussed. PMID- 11197204 TI - Role of chemokines in trafficking of lymphocytes and dendritic cells. AB - Lymphocytes continuously recirculate between the vascular system and tissues. Furthermore, different lineages and subsets are capable of migrating to different tissues and tissue microenvironments. Upon proinflammatory stimulation or antigen loading, immature dendritic cells in the skin and mucosa migrate into the T-cell zones of regional lymph nodes, where they become fully differentiated dendritic cells capable of activating naive T cells. These migratory properties of lymphocytes and dendritic cells, which are essential for the homeostasis and function of the immune system, are regulated by various cell-adhesion molecules and by a group of chemokines collectively called "immune chemokines." These chemokines are expressed constitutively in specific tissue microenvironments within the primary and secondary lymphoid organs, act via highly specific G protein-coupled receptors, and regulate the migration of lymphocytes and dendritic cells to specific tissue microenvironments. Immune chemokines are thus key elements in the genesis, maintenance, and function of the immune system. PMID- 11197205 TI - A chemokine, SDF-1/PBSF, and its receptor, CXC chemokine receptor 4, as mediators of hematopoiesis. AB - A chemokine, stromal cell-derived factor/pre-B-cell growth-stimulating factor (SDF-1/PBSF), and its primary physiologic receptor, CXC chemokine receptor 4 (CXCR4), are essential for B-lymphocyte production and colonization of bone marrow by myeloid lineage progenitors during embryogenesis. Moreover, CXCR4 is an autonomous cell essential for long-term lymphoid and myeloid reconstitution in adult bone marrow. Upregulation of CXCR4 expression may be useful for improving engraftment of repopulating stem cells in clinical transplantation. PMID- 11197206 TI - Roles of chemokines and chemokine receptors in HIV-1 infection. AB - Human immunodeficiency virus type 1 (HIV-1) uses a coreceptor together with CD4 to enter CD4+ target cells. The chemokine receptors CXCR4 and CCR5 have been found to be the major coreceptors for T-cell line-tropic and macrophage-tropic HIV-1 strains, respectively, although many other chemokine and orphan receptors have also been identified as potential coreceptors for HIV-1. Genetic analyses has revealed the importance of chemokine and chemokine receptor genes in disease progression. The discovery of coreceptors provides a more defined scheme for virus entry in which the HIV-1 envelope glycoprotein sequentially binds CD4 and coreceptor, leading to a membrane fusion reaction between the viral envelope and the plasma membrane of the target cell. It also provides the basis for HIV-1 cell tropism. The identification of HIV coreceptors provides new opportunities for the development of anti-HIV therapy. Many coreceptor-based therapeutic approaches have been developed, some of which are currently in clinical trials. PMID- 11197207 TI - Multidrug resistance of acute leukemia and a strategy to overcome it. AB - A representative cause of multidrug resistance (MDR) is expression of the MDR gene (mdr1) and its product P-glycoprotein (P-gp). The function of P-gp is thought to be the extrusion of anticancer drugs from the cell against a concentration gradient. In acute myelogenous leukemia (AML), P-gp expression in leukemic blast cells at initial presentation has been reported to be 20% to 40%. The remission rate of acute leukemia patients is significantly lower in P-gp+ patients than in P-gp- patients. A significantly shorter survival and relapse free survival in P-gp+ AML patients compared with P-gp- patients has been reported. Intracellular daunorubicin/Rhodamine123 content in P-gp+ leukemic blast cells is significantly lower than in P-gp- leukemic blast cells. By using a leukemic blast colony assay, lowered sensitivity to the anticancer drug was revealed not only in leukemic blast cells but also in leukemic progenitors. One method to overcome MDR with a possibility of clinical application is to use drugs that interfere with the function of P-gp. The addition of MS-209 in vitro as an MDR-reversing agent significantly enhanced the intracellular daunorubicin/Rhodamine 123 accumulation and the retention of P-gp+ leukemic blast cells to a level similar to that of P-gp- blast cells. Recent clinical trials using MDR-reversing agents have demonstrated some encouraging results in P-gp+ patients but not in P-gp- patients. PMID- 11197208 TI - Chemoprotective and radioprotective effects of amifostine: an update of clinical trials. AB - Amifostine (Ethyol), the first broad-spectrum cytoprotectant approved in many countries for clinical use, is an analog of cysteamine and was originally developed by the U.S. Walter Reed Army Institute of Research in the 1950s as a radioprotective agent. Studies have shown that amifostine selectively protects normal tissues of various organs from the effects of radiation and multiple cytotoxic chemotherapeutic drugs. Amifostine has demonstrated broad-spectrum cytoprotection against myelotoxicity, nephrotoxicity, xerostomia, and mucositis associated with various chemotherapy and radiation modalities. Amifostine has been evaluated in large comparative clinical trials in patients with advanced ovarian cancer, rectal cancer, and head and neck cancer, and in many phase 2 trials in patients with various neoplastic diseases. These trials have shown that amifostine delivers protection from the cytotoxic effects of cisplatin, cyclophosphamide, and radiation on various organs. Pretreatment with amifostine has also improved salivary gland tolerance of high-dose radioiodine treatment. Recent unique observations include improvement in cytopenia in patients with myelodysplastic syndrome. This review summarizes preclinical and clinical data on amifostine and includes trials that evaluated the drug's chemoprotective and radioprotective effects and other potential uses in clinical oncology. PMID- 11197209 TI - Structure and function of fibrinogen inferred from hereditary dysfibrinogens. AB - The structure-function relationships of human fibrinogen and their clinical implications are discussed on the basis of data provided by biochemical and electron microscopic analyses of normal and abnormal fibrinogen and by recent crystallographic studies on certain functional domains and segments of normal fibrinogen. Particularly, ultrastructure studies of individual fibrinogen molecules and fibrin networks of structurally elucidated dysfibrinogens enable us to understand the structure-function relationships of these dysfibrinogens more clearly than ever. Electron micrographs of some representative dysfibrinogen molecules are provided. PMID- 11197210 TI - Glanzmann thrombasthenia: integrin alpha IIb beta 3 deficiency. AB - Integrins, a family of noncovalently associated alpha beta heterodimeric adhesion receptors, are involved in a variety of pathological and physiological processes. The importance of integrins is evident in the severe pathogenic consequences of their congenital deficiencies: Glanzmann thrombasthenia (GT) and leukocyte adhesion deficiency. In this review, I have focused on GT, a rare autosomal recessive bleeding disorder characterized by the quantitative and/or qualitative abnormality of integrin alpha IIb beta 3 (glycoprotein IIb-IIIa). Molecular genetic analysis of GT, when caused by a quantitative abnormality of alpha IIb beta 3, provides important information regarding key structures for alpha IIb beta 3 biosynthesis. Of particular interest is GT when caused by a qualitative abnormality of alpha IIb beta 3 (GT variants). The analyses of GT variants provide new insight into the regulation of alpha IIb beta 3 function and the interaction between alpha IIb beta 3 and its ligands. This research could contribute to new and better alpha IIb beta 3 antagonists with minimal complications (such as bleeding and thrombocytopenia) for the prevention and treatment of pathological thrombosis. PMID- 11197211 TI - Glycoprotein 130 and c-kit signals synergistically induce thrombopoietin production by hematopoietic cells. AB - We have reported that simultaneous activation of glycoprotein (gp) 130 and c-kit signals by interleukin (IL)-6, soluble IL-6 receptor (sIL-6R), and stem cell factor (SCF) promotes proliferation of human hematopoietic progenitor cells and their differentiation into erythroid, myelocytic, and megakaryocytic cells. We recently found that erythropoietin produced by erythroid progenitors stimulates erythropoiesis via gp130 and c-kit signals. Here we examined thrombopoietin (TPO) production by hematopoietic cells cultured with IL-6, sIL-6R, and SCF. Reverse transcription-polymerase chain reaction analysis indicated that hematopoietic cells generated from cord blood CD34+ cells with the 3 factors expressed a minor splice variant of TPO messenger RNA, P1 delta E2, which can be translated to TPO protein more efficiently than regularly spliced isoforms. The reduction in c-mpl, receptors for TPO, by antisense oligodeoxynucleotides suppressed the generation of erythroid, myelocytic, and pluripotent progenitors in suspension culture, plus colony formation of megakaryocytic progenitors in addition to these progenitors in clonal culture of cord blood CD34+ cells with IL-6, sIL-6R, and SCF. The addition of anti-human TPO antibody to the clonal culture also suppressed colony formation. These findings indicate that TPO production by hematopoietic cells stimulated by IL-6, sIL-6R, and SCF is involved in promoting their own growth. PMID- 11197212 TI - Severe aplastic anemia associated with chronic natural killer cell lymphocytosis. AB - Chronic natural killer (NK) lymphocytosis involves a persistent increase in CD56+ large granular lymphocytes (LGLs) that is sometimes associated with immune mediated complications, such as anemia and neutropenia. However, aplastic anemia (AA) is a rare complication. Here we describe 2 patients with severe AA who presented with persistent increases in NK cells. Their LGLs were positive for CD56, CD16, and intracellular interferon (IFN)-gamma but negative for CD3, Fas ligand, and T-cell receptor rearrangement, findings that are compatible with NK cells. Not only the number of NK cells, but NK activity as well, was increased in both patients. The number of NK cells changed according to hematologic recovery and relapse in 1 case. Thus, there seemed to be a close relationship between NK cells and the progression of AA, at least in this instance. Further investigation of the clinical course of similar cases and the characteristics of NK cells is necessary. PMID- 11197213 TI - Trisomy 11 acute myeloid leukemia: 5 additional cases from the Japan Adult Leukemia Study Group AML-92 and AML-95 databases. AB - We searched for trisomy 11 in acute myelogenous leukemia (AML) patients using the Japan Adult Leukemia Study Group (JALSG) AML-92 and -95 databases to clarify the clinical and hematologic features of a rare numerical chromosome abnormality. Among the sequentially registered patients of JALSG AML-92 (655 patients) and JALSG AML-95 (531 patients), chromosome findings were obtained for 1074 patients (90.6%); we found 5 patients with trisomy 11 as the sole abnormality. The patients were 4 women and 1 man with trisomy 11 AML, all aged more than 45 years (median, 52 years), with 4 M1 morphologies and 1 M2. No patients manifested hepatosplenomegaly or lymph node enlargement, and no central nervous system leukemia or extramedullary lesions were detectable. All showed positivity for CD13 (5/5), CD33 (5/5), CD34 (3/3), CD38 (2/2), and HLA-DR (5/5). Except for 1 patient, all achieved complete remission after 1 course of induction chemotherapy, but 2 relapsed after discontinuation of chemotherapy. A third case of relapse occurred during intensification of chemotherapy, and the patient underwent allogenic bone marrow transplantation but died from interstitial pneumonia. PMID- 11197214 TI - Good prognosis of patients with acute promyelocytic leukemia who achieved second complete remission (CR) with a new retinoid, Am80, after relapse from CR induced by all-trans-retinoic acid. AB - A new synthetic retinoid, Am80, is effective in treating acute promyelocytic leukemia relapsed from all-trans-retinoic acid-induced complete remission (CR). We report here the long-term clinical outcomes of patients who achieved second CR with Am80. Of 24 evaluable patients, 14 achieved a second CR by Am80 therapy. Of those patients, 4 relapsed within 6 months, despite subsequent consolidation chemotherapy. Six patients underwent sibling or unrelated HLA-matched allogeneic bone marrow transplantation (BMT), and 4 are alive without relase for more than 49 months after achieving second CR. Four of 8 patients who did not receive BMT are alive without relapse for more than 49 months. Promyelocytic leukemia retinoic acid receptor alpha (PML-RAR alpha) fusion transcript was undetectable by reverse transcriptase-polymerase chain reaction in all living patients. Therefore, if patients achieve second CR with Am80 and HLA-matched donors are available, BMT is the treatment of choice. However, it is noteworthy that CR was maintained for more than 49 months in half of the patients who did not receive BMT. PMID- 11197215 TI - Lymphoid blast crisis during interferon-alpha therapy in a patient with chronic myelogenous leukemia in myeloid blast crisis. AB - A 47-year-old woman was admitted to the hospital on March 13, 1998, because of general malaise and fever. It was determined that she had chronic myelogenous leukemia (CML) in myeloid blast crisis. Hydroxyurea was started initially, and the blasts completely disappeared from peripheral blood on day 9 of therapy. Interferon (IFN)-alpha was subsequently started, but lymphoblasts newly appeared on day 13 of administration. Treatment with adriamycin, vincristine, and prednisolone (AdVP) was immediately started, which rapidly reduced the lymphoblasts. However, the myeloblasts again began to gradually increase. Subsequent examinations showed the combined presence of myeloblasts and lymphoblasts in the marrow and peripheral blood. The ratio between myeloblasts and lymphoblasts depended on the treatment (IFN-alpha or AdVP). The patient died from respiratory failure on November 16, 1998. This patient may have had an underlying bipotential blastic clone that evolved differently in response to IFN alpha or AdVP. In some CML patients, IFN-alpha may induce lymphoid blast crisis. PMID- 11197216 TI - Clinicopathological analyses of 5 Japanese patients with CD56+ primary cutaneous lymphomas. AB - We analyzed the clinicopathological features of 5 Japanese patients with CD56+ primary cutaneous lymphomas (3 men and 2 women aged 25 to 73 years). Except for 1 patient in whom bone marrow involvement was simultaneously observed, all patients presented with cutaneous lesions. Based on their Epstein-Barr virus (EBV) status, we categorized these patients into 2 groups, namely EBV-encoded small RNA-1 (EBER 1) (3 patients) and EBER-1- (2 patients). Generalized lymphadenopathy and bone marrow involvement were observed only in EBER-1 patients. Morphologically, angiocentric proliferation was more prominent in EBER-1+ patients and was accompanied by panniculitis-like changes. The lymphomas in EBER-1- patients featured monomorphic proliferation of lymphoblastic cells with no cytoplasmic granules. Phenotypically, CD3-, cytoplasmic CD3 epsilon+, and CD56+ were common findings in both types. The EBER-1- type showed an additional distinguishing feature, CD7+, CD4+, CD8-, HLA-DR+, and terminal deoxynucleotidyl transferase positive (TdT+) phenotype. The lymphoma was primarily resistant in the EBER-1+ type, and the patients died within 6 months of admission. In contrast, the lymphoma in the EBER-1- patients was originally chemosensitive. Collectively, we consider there to be at least 2 types of CD56+ primary cutaneous lymphomas, corresponding to nasal-type natural killer (NK)/T-cell lymphomas (EBER-1+) and blastic NK-cell lymphomas (EBER-1-). PMID- 11197217 TI - Anti-apoptotic role of Bfl-1 in staurosporine-treated B-lymphoblastic cells. AB - To examine the relationship between the expression level of Bfl-1 and the susceptibility to staurosporine-induced apoptosis in B-lymphoblastic cells, we tested cell survival in 4 cell lines: 2 that are Bfl-1-nonexpressing (Reh and JM 1) and 2 that are Bfl-1-expressing (IM-9 and Wil2-NS). Reh and JM-1 showed apoptosis levels of 62% (Reh) and 30% (JM-1) as early as 3 hours after treatment with staurosporine, whereas IM-9 and Wil2-NS showed apoptosis levels of only 40% and 26%, respectively, even after 1 day of treatment with staurosporine. Either induced expression of Bfl-1 with 12-o-tetradecanoyl phorbol-13-acetate or exogenous expression of Bfl-1 by transfection in Reh cells promoted cell survival. These results suggest that expression of Bfl-1 contributes to regulating apoptosis in the B-cell lines we examined. PMID- 11197218 TI - Successful treatment of multiple myeloma--associated amyloidosis by interferon alpha, dimethyl sulfoxide, and VAD (vincristine, adriamycin, and dexamethasone). AB - A 45-year-old Japanese man was admitted to our hospital because of a mass in the submandibular region, abnormal hematologic findings, and proteinuria. A diagnosis of multiple myeloma was made based on the results of bone marrow analysis and M protein in hematologic tests, and a diagnosis of amyloidosis was made on the basis of deposition of amyloid in the rectal submucosal and lip tissues and the mass in the submandibular region. Combination therapy of interferon (IFN)-alpha at 1-day intervals and daily oral dimethyl sulfoxide (DMSO) and vincristine, adriamycin, and dexamethasone (VAD) resulted in a marked decrease in the size of the mass and hypertrophy of the back, as well as a decrease in the levels of plasma cells in bone marrow and of M-protein and immunoglobulin G in serum. The results of this case indicate that long-term administration of IFN-alpha and DMSO with VAD is effective in treating amyloidosis with multiple myeloma. PMID- 11197219 TI - Successful treatment of disseminated Fusarium infection in an infant with leukemia. AB - Disseminated Fusarium infection in an immunocompromised host is intractable and results in high mortality. We provide the first full case report on successful treatment of a disseminated Fusarium infection in an infant. The 6-month-old infant, whose family raised livestock, had infantile leukemia. During the neutropenic period after intensive chemotherapy, vomiting, diarrhea, fever, subcutaneous nodes, and coughing appeared. Pneumonia was diagnosed, and Fusarium moniliforme was isolated from blood culture. A central venous catheter was removed. Granulocyte colony-stimulating factor (G-CSF) and amphotericin B (AMPH B) (total dose, 65 mg/kg) were administered continuously for 8 weeks. The infection was resolved according to improvement of clinical and laboratory findings, and intensive chemotherapy was restarted for the leukemia. Cord blood stem cell transplantation from an unrelated donor was performed. The Fusarium infection did not recur, but after transplantation, leukemia relapsed. Treatment of neutrophils using G-CSF, AMPH-B, and local treatment induced resolution of the disseminated Fusarium infection in this immunocompromised host with malignancy. We suggest caution for patients living in an environment conducive to the development of Fusarium infection because of the particular risk of infection. PMID- 11197220 TI - Successful engraftment of allogeneic peripheral blood stem cell transplant after nonmyeloablative preparative regimen with cytarabine and cyclophosphamide: report of 2 cases. AB - We report our experience with allogeneic peripheral blood stem cell transplantation (allo-PBSCT) following a nonmyeloablative conditioning regimen consisting of cytarabine (8 g/m2) and cyclophosphamide (120 mg/kg) in the treatment of 2 patients aged 50 and 55 years with refractory chronic myelomonocytic leukemia and chronic myeloid leukemia in accelerated phase, respectively. Our nonmyeloablative regimen was well tolerated by older patients at high risk of regimen-related toxicity by the conventional conditioning regimen but was immunosuppressive enough to achieve mixed chimerism. After allo-PBSCT, we monitored chimerism in these patients by fluorescence in situ hybridization using X- and Y-specific probes and polymerase chain reaction-based analysis of a variable number of tandem repeats. We found that full chimerism and graft-versus leukemia (GVL) effects could be induced in these patients by donor lymphocyte infusions and withdrawal of posttransplantation immunosuppressive therapy. Our observations suggest that a nonmyeloablative conditioning regimen can establish mixed chimerism and that donor lymphocyte infusion may induce GVL effects in older patients at high risk of regimen-related toxicity. PMID- 11197221 TI - Successful allogeneic bone marrow transplantation in a case of adult precursor B lymphoblastic lymphoma. AB - A 42-year-old woman was admitted to the National Cancer Center Hospital in Tokyo, Japan, because of lumbago and bilateral leg pain. Clinical examination revealed a retroperitoneal bulky tumor, a breast tumor, and lymphoblasts in bone marrow. She did not have surface lymph node swelling or systemic symptoms such as weight loss and night sweats. Lymphoblasts in bone marrow were positive for CD10 and CD19 but negative for CD20, surface immunoglobulin, and T-cell antigens. Needle biopsy of a retroperitoneal mass revealed diffuse infiltration of lymphoblastic tumor cells. Because the cells were immunoreactive for CD79a, CD10, and terminal deoxynucleotidyl transferase, the patient was diagnosed as having precursor B lymphoblastic lymphoma (which is rare in adults) with bone marrow involvement. The patient achieved complete remission by an induction therapy for acute lymphoblastic leukemia, underwent allogeneic bone marrow transplantation, and has remained in complete remission for more than 3 years. PMID- 11197222 TI - Circulating adhesion molecules in patients with stable coronary artery disease. AB - To evaluate platelet and endothelial function in patients with stable coronary artery disease (CAD), we investigated levels of the plasma-soluble (s) adhesion molecules E-selectin (sE-selectin), P-selectin (sP-selectin), and intercellular adhesion molecule-1 (sICAM-1) in 74 patients (mean age, 53 +/- 8 years) with angiographically documented coronary artery disease. Levels were compared to 27 matched healthy control subjects. Patients were excluded if they had recent cardiovascular events or any illness that might influence platelet and endothelial cell function. Concentrations of sP-selectin were significantly higher in patients with stable CAD (276 +/- 61 ng/mL) compared with control subjects (188 +/- 32 ng/mL) (P = .0001), whereas sE-selectin and sICAM-1 levels were similar between the 2 groups. Pooling both groups showed that sICAM-1 correlated weakly with triglycerides (r = 0.240, P = .01) and sP-selectin correlated weakly with low-density lipoprotein cholesterol (r = 0.204, P = .04). Although plasma sICAM-1 concentrations were significantly increased in hypercholesterolemic patients compared with those of normocholesterolemic patients (P = .04), sP-selectin and sE-selectin levels were similar between the 2 groups. In conclusion, significantly increased sP-selectin levels, indicating platelet activation, were found in patients with stable CAD. No other sign of endothelial cell activation in these patients could be detected. Moreover, sP selectin levels seem to reflect the activation of platelets rather than of endothelial cells. PMID- 11197223 TI - A new mutation, Ala1500-->Glu, responsible for type 2A von Willebrand disease. AB - Two patients (from the same family) with a bleeding disorder were diagnosed with type 2A von Willebrand disease (vWD). The 28th exon of the von Willebrand factor (vWF) gene was obtained by polymerase chain reaction and then screened by denaturing gradient gel electrophoresis. The fragments displaying abnormal melting behavior were directly sequenced. A heterozygous C-->A substitution changing alanine 1500 to glutamic acid at position 4750 in the A2 domain of vWF was found. The structure of recombinant A1500E vWF within transfected COS-7 cells and the secretion of high-molecular-weight (HMW) multimers were similar to wild type vWF. HMW forms of vWF multimers were absent in plasma but present in platelets. The mutation described here corresponds to the group II type 2A vWD characterized by normal secretion of all vWF multimers. PMID- 11197225 TI - Transformation of polycythemia vera to acute promyelocytic leukemia. PMID- 11197224 TI - Transient factor VIII inhibitor in a hemophilia patient after staphylococcal septic shock syndrome. AB - We report a transient type I factor VIII inhibitor that arose in a 30-year-old hemophilia patient just after staphylococcal septicemia. This situation usually occurs early in the course of substitution therapy with factor VIII concentrate in hemophilia patients. Although disseminated intravascular coagulation and acute respiratory distress syndrome developed after septic shock, the patient recovered following intravenous administration of antibiotics (meropenem and gentamycin), an antithrombin preparation, high-dose methylprednisolone, and recombinant factor VIII concentrate (rFVIII). During this therapy, however, activated partial thromboplastin time gradually lengthened. On the seventh day of hospitalization, intracranial hemorrhage occurred with right hemiplegia, even though the substitution therapy had continued at the same dosage (30 U/kg per day) of rFVIII. At that point, 4 Bethesda units of the type I inhibitor against factor VIII were detected in the plasma. Increased amounts (46 U/kg per day) of rFVIII and prednisolone were administered, and hypothermic therapy was initiated. Following these treatments, the patient's general condition gradually improved, and within 25 days the inhibitor titer dropped to undetectable levels and did not recur during treatment. These clinical findings suggest that the staphylococcal septic shock may have acted as a trigger in the development of transient factor VIII inhibitor in this patient. PMID- 11197226 TI - Second International Symposium on Myelodysplastic Syndromes in Childhood. AB - This article summarizes presentations from the Second International Symposium on Myelodysplastic Syndromes in Childhood, May 11 to 14, 2000, in Funen, Denmark. Topics included epidemiology, pathology, pathophysiology, cytogenetics, congenital neutropenia, transplantation, and classification. Dr. Henrik Hasle was the Meeting Chair and Dr. Gitte Kerndrup was the Co-Chair. PMID- 11197227 TI - Ultrastructure of the pellicle of Euglena gracilis. AB - Deep-etching technique was used to investigate the organization of the pellicle complex of Euglena gracilis. The interpretation of the images was further supported by SEM and TEM investigations. Our results mainly validate data obtained by previous freeze-fracture studies on the E and P faces of the outer cortical membrane. At the level of the ridges, the outer E fracture face is highly organized in a regular striated pattern, whereas the P inner face shows a particulate structure. However, our images reveal that this particulate organization of the P face is not limited to the ridges, but it is displayed also by the grooves. Moreover, this face shows two distinct layers, a particulate layer facing the cytoplasm and a striated layer facing the E face; these layers represent different true fracture levels of the same P face. PMID- 11197228 TI - Apoptosis and mitosis of parenchymal cells in the duct-ligated rat submandibular gland. AB - Apoptosis and proliferation of parenchymal cells during atrophy of rat submandibular gland induced by double duct ligation were investigated using immunohistochemistry for proliferating cell nuclear antigen (PCNA), terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labelling (TUNEL) and transmission electron microscopy (TEM). At 2 and 3 days after ligation, increased PCNA positive cells and mitoses were seen in ducts; thereafter PCNA positive cells decreased in number. At 3 and 4 days, the acinar cell population rapidly decreased, with many remaining TUNEL positive acinar cells. During this period, TEM showed typical apoptotic acinar cells that were phagocytosed by adjacent acinar cells or intraepithelial macrophages. After 7 days, most acinar cells had disappeared, leaving prominent residual ducts; a few acinar cells remained, especially at the lobule periphery. Submandibular gland duct ligation thus induced marked depletion of acinar cell by apoptosis and a concurrent short-lived cycle of duct cell proliferation. PMID- 11197229 TI - 20-Hydroxyecdysone-induced differentiation and apoptosis in the Drosophila cell line, l(2)mbn. AB - 20-Hydroxyecdysone has an inhibitory effect on the proliferation of l(2)mbn cells, causes vacuolization and fragmentation of cells, and promotes a strong phagocytotic activity. From several lines of evidence, it can be concluded that 20-hydroxyecdysone induces apoptosis. Long-term video observations following the fate of individual cells, scanning and transmission electron microscopy reveal the typical characteristics of apoptosis: sequestration of small cellular protuberances or larger parts of the cell with nuclear fragments (apoptotic bodies), chromatin condensation, condensation and vesiculation of cytoplasm, whereas the mitochondria retain their normal appearance. The induction of apoptosis by 20-hydroxyecdysone was confirmed by the TUNEL reaction and quantitatively determined by a method based on this reaction. Onset of apoptosis precedes phagocytotic activity. JH III alone has no clear-cut effect on l(2)mbn cells. In double treatments, the inhibitory effect of 20-hydroxyecdysone on cell proliferation is significantly reduced by the addition of JH III. Whether or not JH III also reduces apoptotic activity is not yet clear. It is shown that the l(2)mbn cell line is an advantageous model system for the exploration of steroid induced apoptosis. PMID- 11197230 TI - Swelling of the collagen-keratocyte matrix of the bovine corneal stroma ex vivo in various solutions and its relationship to tissue thickness. AB - AIM: The mammalian corneal stroma, like some other connective tissues, can absorb fluid, swell and become oedematous. Since studies on the corneal stroma have been carried out with different types of preparations and solutions, inter-study comparisons are very difficult. A study was thus undertaken on a standardised preparation to assess the relative magnitude of this swelling and its relationship to thickness of the preparations. METHODS: From selected recent post mortem eyes of adult cattle, stroma preparations were cut from the central part of the cornea. These preparations were immersed in various solutions of known pH and osmolality, and the time-dependent changes in wet mass were assessed over 9 h at 37 degrees C. The relative rates and magnitude of the swelling of the tissue were then compared. RESULTS: A reference value for stromal swelling was obtained by incubation in a 35 mM bicarbonate-buffered mixed salts solution equilibrated with 5% CO2-air (pH 7.60) where a 3.39-fold increase in wet mass and a 4.58-fold increase in thickness was realised in 9 h, at an initial rate of 76 +/- 3%/h. The swelling was essentially the same in an organic buffer-mixed salt solution (pH 7.5) but progressively greater in phosphate-buffered saline (pH 7.5), a range of phosphate buffers (10-67 mM, pH 7.5), NaCl solutions (0.025-1%) and with gross swelling observed in water (where a 15.9-fold increase in wet mass occurred along with a 25-fold increase in thickness, at an initial rate of 643 +/- 62%/h). Overall, the wet mass changes were strongly related to thickness (P < 0.001). CONCLUSIONS: The results confirm that the selection of solution(s) for studies on corneal stromal swelling is critical. The swelling (oedema) is lower in a physiologically-relevant solution (similar to the aqueous humour of the eye). This indicates that the swelling tendency of the corneal stroma has been overestimated in the past, and that a similar discrepancy may also exist for studies on other connective tissues ex vivo when non-physiological experimental solutions are used. PMID- 11197231 TI - Study of the microbial aggregation in Mycobacterium using image analysis and electron microscopy. AB - Cellular aggregation, which occurs in both prokaryotes and eukaryotes, is controlled by the hydrophobicity as well as the electrokinetic potential of the cell surface and substratum. It is known that the Mycobacterium genus form aggregates, but the influence of sugar on the cellular aggregation has not been reported for this genus. The mutant strain Mycobacterium sp. MB-3683 that transforms sterol to androstenedione (AD), a steroidal precursor used by the pharmaceutical industries, was employed in this study. This strain was cultivated in a synthetic medium on three sugars (glycerol, glucose and fructose) at different concentrations, and at 144 h microbial growth, cellular aggregation, hydrophobicity, lipid content, fatty acid composition, and width of cellular walls were measured. It was observed that at different sugar concentrations, similar growth and pH were obtained. However, in fructose, the aggregation level was significantly high, followed by glycerol and glucose (fructose < glycerol < glucose). These results were confirmed using electron microscopy and the aggregate area quantified by image analysis. Hydrophobicity was the highest in fructose and the lowest in glucose. The total lipids, in contrast to cellular hydrophobicity, were higher in glucose than glycerol. Although, the hydrophilic lipophilic balance (HLB) of principal fatty acids isolated was similar regardless of sugar used. In glycerol and fructose, the paraffins were observed, which are responsible for the high cellular hydrophobicity detected above. The width of cell wall of the organisms grown on glucose and fructose was similar, but in glycerol the walls were very thin. There is a correspondence between cell wall width and lipid content. PMID- 11197233 TI - Ultrastructural study of acrosome formation in mongolian gerbil (Meriones unguiculatus). AB - Spermatogenesis is a complex and very well organized process lasting from 30 to 75 days in mammals. The spermatogenic process has been described mainly in laboratory mammals, such as the rat, while correspondent studies in wild animals are scarce. The gerbil (Meriones unguiculatus) is a small rodent native of the arid regions of Mongolia and China. Few reports are available on reproduction in the male Mongolian gerbil. The present study provides the first description of the ultrastructural alterations in spermatid cytoplasm and nucleus, with particular reference to acrosome formation in gerbils. The testes were processed by conventional transmission electron microscopy technique. Based on the development of the acrosomal system and changes in nuclear morphology, the transformation of spermatids in spermatozoon was divided into 15 steps. There were four phases in the spermiogenesis process in the gerbil: Golgi, cap, acrosomal and maturation phases. This provides the foundation for a variety of future studies of the spermiogenesis of this animal. PMID- 11197232 TI - Regulation of acrosome formation in mice expressing green fluorescent protein as a marker. AB - Transgenic mice expressing enhanced green fluorescent protein under acrosin promoter were used to study the role of the Golgi complex and of the cytoskeleton during early development of the acrosomic system in exactly defined stages of the seminiferous epithelial cycle during in vitro differentiation. First acrosin expression was found uniformly in the cytoplasm of stage IV pachytene spermatocytes. The steady-state level increased up to stage X pachytene spermatocytes, and in diakinetic primary spermatocytes, acrosin started to accumulate into the Golgi complex. During step 2 of spermiogenesis, several small fluorescent proacrosomic granules were seen in various parts of the Golgi complex, and they fused to a solid acrosomic system at step 3. In cultured stage I-III seminiferous tubule segments, nocodazole slowed down acrosin incorporation and increased the distance of the acrosomic system from the nucleus. Follicle stimulating hormone had an opposite effect by increasing density of the acrosomic system together with activation of the surrounding microtubule network. The observations suggest that microtubules have an important function during the early differentiation of the acrosomic system. PMID- 11197234 TI - Ultrastructural characterization of the isolated hydrogenosome in Tritrichomonas foetus. AB - In the present study we show new aspects of the hydrogenosome ultrastructure as well alterations induced by the fractionation technique. The morphology of freshly isolated hydrogenosomes as well those found in whole cells of Tritrichomonas foetus were examined in thin-sections, in replicas of fast freezing, and conventional freeze-fracture, freeze-etching, and by high resolution scanning electron microscopy (field emission in-lens scanning electron microscopy). The true surface as well the concave and convex fracture faces of the inner and outer membranes are shown. We showed that after fractionation procedures the hydrogenosome ultrastructure can be changed, since isolated hydrogenosomes present patchwork-like structures, rosettes and the inner hydrogenosomal membrane is displaced. The peripheral vesicle is seen as a distinct compartment, since its content and morphological appearance is quite different from the rest of the organelle. The peripheral vesicle shows a smooth surface but presenting pores with 20 nm in diameter with a density of 7/micron 2 when observed after freeze-etching. We report the existence of characteristic intramembrane particles distribution and density on hydrogenosome membranes of isolated and whole T. foetus, suggesting that this organelle can have its morphology changed as consequence of technical modifications or as expression of its metabolic state. PMID- 11197235 TI - The osteochondral ligament: a fibrous attachment between bone and articular cartilage in Rana catesbeiana. AB - The anuran epiphyseal cartilage shows a lateral expansion that covers the external surface of the bone, besides other features that distinguish it from the corresponding avian and mammalian structures. The fibrous structure that attaches the lateral cartilage to the bone was characterized in this work. It was designated osteochondral ligament (OCL) and presented two main areas. There was an inner area that was closer to the periosteal bone and contained a layer of osteoblasts and elongated cells aligned to and interspersed with thin collagen fibers. The thin processes of the cells in this area showed strong alkaline phosphatase activity. The outer area, which was closer to the cartilage, was rich in blood vessels and contained a few cells amongst thick collagen fibers. TRITC phaloidin staining showed the cells of the inner area to be rich in F-actin, and were observed to form a net around the cell nucleus and to fill the cell processes which extended between the collagen fibers. Cells of the outer area were poor in actin cytoskeleton, while those associated with the blood vessels showed intense staining. Tubulin-staining was weak, regardless of the OCL region. The main fibers of the extracellular matrix in the OCL extended obliquely upwards from the cartilage to the bone. The collagen fibers inserted into the bone matrix as Sharpey's fibers and became progressively thicker as they made their way through the outer area to the cartilage. Immunocytochemistry showed the presence of type I and type III collagen. Microfibrils were found around the cells and amongst the collagen fibrils. These microfibrils were composed of either type VI collagen or fibrilin, as shown by immunocytochemistry. The results presented in this paper show that the osteochondral ligament of Rana catesbeiana is a complex and specialized fibrous attachment which guarantees a strong and flexible anchorage of the lateral articular cartilage to the periosteal bone shaft, besides playing a role in bone growth. PMID- 11197236 TI - Peptic ulcer bleeding. PMID- 11197237 TI - Endoscopic surveillance and ablative therapy for periampullary adenomas. AB - OBJECTIVES: Periampullary adenomas are an increasingly recognized condition, both in those with familial adenomatous polyposis syndromes (FAP) as well as sporadic cases. Endoscopic management has been advocated for these lesions without differentiating between these two patient groups regarding aim of therapy. The aims of this study were to determine the safety and effectiveness of endoscopic surveillance and ablative therapy of periampullary adenomas in patients with both sporadic and FAP-associated lesions. METHODS: Retrospective analysis of 59 patients with FAP and 32 with sporadic lesions who were all enrolled in a program of endoscopic surveillance and ablative therapy. Median follow-up was 24 months (range, 1-134 months). RESULTS: Ampullary ablative therapy has resulted in return to normal histology in 44 and 34% of sporadic and FAPassociated lesions, respectively. Complications of endoscopic therapy were mild in 12 patients and severe in 3 patients: the latter category involved one occurrence of asymptomatic duodenal stenosis and one occurrence of postcoagulation syndrome--both after Nd YAG laser therapy-and necrotizing pancreatitis after ampullary biopsy in one patient. Thirteen patients have been referred for surgical intervention. There has been no mortality and no cases of advanced malignancy missed by endoscopy. CONCLUSIONS: Endoscopic surveillance and ablative therapy of periampullary lesions is safe and can be effective, although eradication of ampullary tissue requires multiple ablative sessions. PMID- 11197238 TI - The effect of the modified puestow procedure on diabetes in patients with tropical chronic pancreatitis--a prospective study. AB - OBJECTIVES: Surgical decompression of the pancreatic duct in patients with chronic pancreatitis relieves pain in 80-90% of subjects, but its effect on exocrine and endocrine pancreatic function is not clear. We sought to further examine such effects. METHODS: We performed the modified Puestow procedure (lateral pancreaticojejunostomy) in 53 patients with chronic tropical pancreatitis. Pain evaluation was done subjectively and objectively, and the fasting and postprandial blood glucose, insulin requirements, and 72-h fecal fat levels were estimated before and at 3 months and 5 yr after operation. We compared 46 operated patients who completed 5 yr of follow-up with 40 patients who did not undergo operation. RESULTS: Forty-one patients (89%) had complete pain relief. The mean fasting (209 mg/dl) and postprandial (320 mg/dl) blood glucose and insulin requirements (40 U/day) decreased postoperatively (fasting, 162 mg/dl; postprandial blood glucose, 254mg/dl; insulin requirement, 18.2 U/day; p < 0.01), and steatorrhea improved in one of six patients. In the nonoperated group, endocrine and exocrine pancreatic function remained unchanged. CONCLUSIONS: Patients with tropical chronic pancreatitis who undergo the Puestow procedure not only have relief from pain but also improvement of diabetes. PMID- 11197239 TI - Osteoporosis in a north american adult population with celiac disease. AB - OBJECTIVE: Osteoporosis, common in European and South American adults with celiac disease, has not been reported in those patients with celiac disease residing in North America. We therefore evaluated bone density in a group of patients from the United States. METHODS: Patients (105 women and 23 men) with celiac disease, who had completed a questionnaire and had bone mineral density (BMD) measured by dual energy x-ray absorptiometry, were evaluated. The patients were an average age of 56 yr old (range 21-83 yr) and had been on a gluten-free diet from 0 months to 46 yr (mean 7.5 yr). RESULTS: Osteoporosis (T score < -2.5) was present in 34% of the patients at the lumbar spine, 27% at the femoral neck, and 36% at the radius. Low bone mass (T score between -1.0 and -2.5) was present in 38% at the lumbar spine, 44% at the femoral neck, and 32% at the radius. When compared to age-matched controls, men were more severely affected than women. BMD did not differ between those on a gluten-free diet and those who had not begun therapy. BMD was remeasured 16 +/- 2 months after beginning a gluten-free diet in 5 patients; it increased by 7.5% at the femoral neck (p < 0.02). In 16 patients who had followed a gluten-free diet for an average of 12 yr, BMD remained stable over an additional 2 yr of observation. CONCLUSIONS: Osteoporosis and low bone mass often affect North American adults with celiac disease, whether or not they are on dietary therapy. Routine screening for osteoporosis is indicated in patients with celiac disease. PMID- 11197240 TI - Prevalence of IgA-antiendomysial antibody in asymptomatic low bone mineral density. AB - OBJECTIVE: Celiac disease (CD) is a relatively common gastrointestinal disorder that can be asymptomatic. However, even among asymptomatic patients a long-term reduction in bone mineral density (BMD) is found. Excellent noninvasive screening tests for CD are now available. Studies using older screening techniques have suggested a 10-fold increased prevalence of CD among patients with low BMD, but this has not been confirmed with current testing methodology. We set out to confirm these prevalence estimates using antiendomysial antibody testing. METHODS: A total of 100 consecutive patients referred to our outpatient endocrinology clinic for evaluation of idiopathic low BMD were studied. In addition to the routine evaluation, patients completed a symptom questionnaire and underwent serological testing for the presence of the IgA antiendomysial antibody (EMA). All patients with a positive EMA underwent small bowel biopsy and permeability studies. RESULTS: EMA results were available on 96 patients; 78/96 patients were female and the mean age was 57 yr (range 18-86 yr). Seven of 96 (7.3% [95% CI 2.1-12.5%]) were EMA-positive, but all tests were low titer (< or = 1:20). However, none of the biopsies showed any histopathological features of CD, nor did EMA status correlate with any of the clinical or laboratory features assessed. CONCLUSIONS: Despite a high rate of weakly positive antibody tests, our data do not support an increased prevalence of CD among asymptomatic patients referred for evaluation of low BMD. Without an increase over the background prevalence, the high cost of EMA testing argues against routine use of this test for screening of this population. PMID- 11197241 TI - Characteristics of adult celiac disease in the USA: results of a national survey. AB - OBJECTIVE: The clinical spectrum of adults with celiac disease in the United States, where the disease is considered rare, is not known. We sought this information by distributing a survey. METHODS: A questionnaire was distributed by way of a celiac newsletter, directly to celiac support groups, and through the Internet. RESULTS: Respondents (1,612) were from all United States except one. Seventy-five percent (1,138) were biopsy proven. Women predominated (2.9:1). The majority of respondents were diagnosed in their fourth to sixth decades. Symptoms were present a mean of 11 yr before diagnosis. Diarrhea was present in 85%. Diagnosis was considered prompt by only 52% and 31% had consulted two or more gastroenterologists. Improved quality of life after diagnosis was reported by 77%. Those diagnosed at age > or = 60 yr also reported improved quality of life. Five respondents had small intestinal malignancies (carcinoma 2, lymphoma 3) accounting for a relative risk of 300 (60-876) for the development of lymphoma and 67 (7-240) for adenocarcinoma. CONCLUSIONS: Patients with celiac disease in the United States have a long duration of symptoms and consider their diagnosis delayed. Improved quality of life after diagnosis is common. An increased risk of developing small intestine malignancies is present. PMID- 11197242 TI - Efficacy of gluten-free diet alone on recovery from iron deficiency anemia in adult celiac patients. AB - OBJECTIVE: Iron deficiency anemia has been reported as the most frequent extraintestinal symptom in adult celiac disease. Prospective studies on the effect of gluten-free diet on recovery from iron deficiency anemia are lacking. The aim of this study was to verify in adult patients with celiac disease the efficacy of and the time course of recovery from iron deficiency anemia by a gluten-free diet alone. METHODS: We studied 190 consecutive adult patients with iron deficiency anemia, screened for celiac disease by duodenal biopsies. New diagnosed celiac patients were invited to follow a gluten-free diet alone without iron supplementation. After 6 months of diet, duodenal biopsies were performed and hematological tests were repeated at 6, 12, and 24 months. RESULTS: Celiac disease was diagnosed in 26 (24 women, 2 men; 13.7%) adult patients. After 6 months of gluten-free diet 14 of 18 (77.8%) female patients recovered from anemia, but only 5 of 18 (27.8%) reversed from iron deficiency. At 12-month control all but one patient (94.4%) recovered from anemia and 9 patients (50%) from iron deficiency. After 24 months of diet, only the patient who did not recover from anemia at 12-month control was still anemic, whereas 10 patients (55.5%) reversed from iron deficiency. A significant inverse correlation (r = 0.7141, p = 0.0003) between increase of Hb concentrations and decrease of individual histological scores of duodenitis was observed. CONCLUSIONS: A screening for celiac disease should be carried out in adult patients with iron deficiency anemia. Recovery from anemia occurs between 6 and 12 months on a gluten-free diet alone as a consequence of normalization of histological alterations of the intestinal mucosa. PMID- 11197243 TI - Celiac sprue: another autoimmune syndrome associated with hepatitis C. AB - OBJECTIVE: Celiac sprue is being diagnosed with increasing frequency by screening individuals with epidemiologically associated autoimmune syndromes. We sought to test our hypothesis that hepatitis C also may predispose to celiac sprue because it can trigger autoimmune reactions. METHODS: Two hundred fifty-nine consecutively evaluated patients with chronic hepatitis C infection, 59 with autoimmune liver disease, 137 with other hepatic diseases, 356 with various GI syndromes, and 221 normal volunteers underwent serologic screening for celiac sprue. Patients with antigliadin, antiendomysial, and antitissue transglutaminase antibodies in serum underwent duodenoscopy and biopsy. RESULTS: There was a statistically significantly higher prevalence of antigliadin antibody in all groups of patients with liver disease compared with GI controls and normal controls. However, only patients with hepatitis C (n = 3; 1.2%) or autoimmune liver disease (n = 2; 3.4%) had antiendomysial/antitissue transglutaminase antibody in serum. One of 221 normal volunteers (0.4%) was antigliadin, antiendomysial, and antitissue transglutaminase positive; this individual also was found to have hepatitis C (previously undiagnosed). Each of these six individuals had mild intestinal symptoms, duodenal histopathology consistent with celiac sprue, and the celiac-associated HLA-DQ2 allele. Five of the six followed a prescribed gluten-free diet and experienced symptomatic improvement. CONCLUSION: Celiac sprue is epidemiologically associated with chronic hepatitis C infection and with autoimmune liver disease. Because hepatitis C is much more frequently encountered than autoimmune liver disease, hepatitis C appears to be the most common hepatic disease associated with the development of celiac sprue. PMID- 11197244 TI - High prevalence of thrombophilic genotypes in patients with acute mesenteric vein thrombosis. AB - OBJECTIVES: Mesenteric vein thrombosis is a rare but severe abdominal emergency, often requiring intestinal resection. New genetic prothrombotic defects such as factor V Leiden, the prothrombin transition G20210A, and the methylenetetrahydrofolate reductase TT677 genotype have been described in association with venous thrombosis. Our goal was to assess prevalence and clinical significance of genetic thrombophilia in mesenteric vein thrombosis. METHODS: Twelve patients with acute mesenteric vein thrombosis were compared with 431 healthy people from the same geographical area. The factor V Leiden, the prothrombin transition G20210A, and the methylenetetrahydrofolate reductase TT677 genotype were identified by polymerase chain reaction and restriction analysis. RESULTS: A thrombophilic genotype was present in 9 patients (75%): the methylenetetrahydrofolate reductase TT677 genotype was present in 6 (50%), the factor V Leiden in 3 (25%), and the prothrombin transition G20210A in 3 (25%). Combined mutations were present in 4 (33%) patients. CONCLUSIONS: The factor V Leiden, the prothrombin transition G20210A, and the methylenetetrahydrofolate reductase TT677 genotype are important predisposing factors in the pathogenesis of mesenteric vein thrombosis. Their identification bears strong clinical implications for management of patients with mesenteric vein thrombosis. PMID- 11197245 TI - IL-15 drives the specific migration of CD94+ and TCR-gammadelta+ intraepithelial lymphocytes in organ cultures of treated celiac patients. AB - OBJECTIVES: Celiac disease (CD) is an under-diagnosed but extremely frequent disease, triggered by the ingestion of gliadin. The pathogenic mechanisms of CD are still poorly understood, but intraepithelial lymphocytes are considered to have a key role. We intended to define the subsets of T lymphocytes migrating upon gliadin challenge in organ cultures of treated celiac patients and establish the type of factor(s) driving such an infiltration. METHODS: Duodenum biopsies from 10 treated celiacs and 7 controls were cultured in vitro with/without gliadin digest (1 mg/ml) or interleukin (IL)-15 (10 ng/ml). In 7 treated celiacs IL-7, IL-4, and IL-2 were similarly tested. Intraepithelial CD3, CD8, TCR gammadelta, and CD94 were detected by immunohistochemistry and numbered per mm epithelium. RESULTS: IL-15 but not IL-7, IL-4, or IL-2 induced intraepithelial increase of CD3+ and CD8+ cells in celiac and control intestine (p < 0.001 vs cultures with medium). IL-15 induced increases in the number of intraepithelial TCR- gammadelta+ and CD94+ cells only in celiacs (p < 0.001). IL-7 was also effective in increasing intraepithelial TCR-gammadelta+ (but not CD94+) cells in celiac biopsies (p < 0.001). Gliadin induced intraepithelial migration of CD3+, CD8+ (p < 0.001), and CD94+ (p < 0.05) cells in celiacs, but not in controls. CONCLUSIONS: The results we describe in this report indicate that IL-15 might have a key role in modulating and driving intraepithelial infiltration and ultimately in the pathogenesis of CD. PMID- 11197246 TI - Influence of psychiatric diagnoses on interferon-alpha treatment for chronic hepatitis C in a veteran population. AB - OBJECTIVE: The prevalence of psychiatric problems and substance abuse is high in the veteran population with hepatitis C. The purpose of this study was to retrospectively analyze the effect of preexisting psychiatric conditions in veteran patients undergoing treatment with interferon a-2b (IFN-alpha) with respect to adverse events, compliance, and treatment response. METHODS: Thirty three veterans with chronic hepatitis C were treated with IFN-alpha (5 million units three times weekly) for 6 months, followed by a tapering dose for an additional 6 months. All patients fulfilled standard criteria for treatment eligibility. Psychiatric diagnoses, adverse events, and virological and biochemical responses to therapy were determined. RESULTS: Nineteen of 33 (58%) patients with hepatitis C had documented psychiatric conditions before starting IFN-alpha therapy. Of the patients with preexisting psychiatric diagnoses, 13/19 (68%) developed major adverse events requiring intervention or discontinuation of therapy. In contrast, 4/14 (29%) patients without psychiatric diagnoses developed major adverse events (p = 0.024) In the psychiatric group, 6/19 (32%) developed major neuropsychiatric side effects compared with 2/14 patients (14%) in the nonpsychiatric group (p = 0.25). Patients with and without psychiatric diagnoses had equivalent biochemical and virological responses to therapy. Overall, only 2/33 (6%) patients had a sustained virological response. CONCLUSIONS: Veterans with chronic hepatitis C and psychiatric diagnoses experienced a significantly greater number of major adverse events during treatment with IFN-alpha. Veteran patients with hepatitis C should be carefully screened for psychiatric conditions and may require more intensive monitoring during IFN-alpha therapy. PMID- 11197247 TI - Apoptosis in gastric epithelium induced by Helicobacter pylori infection: implications in gastric carcinogenesis. AB - OBJECTIVES: Helicobacter pylori is an identified carcinogen for gastric cancer, however, the underlying mechanisms remain to be defined. In this review, we sought to elucidate the role of apoptosis in gastric carcinogenesis, to determine the influence of H. pylori infection on apoptosis, and finally to provide insights into the mechanisms by which H. pylori may lead to gastric carcinogenesis. METHODS: A broad-based MEDLINE and Current Contents literature search was performed to identify relevant publications between 1966 and March 2000 addressing H. pylori infection, apoptosis, cell proliferation, gastric carcinoma, oncogenes, and tumor suppressor genes, as well as the products of these genes. Abstracts from recent major conferences that provided adequate additional data were also included. RESULTS: Apoptotic cells are rare in the glandular neck region (the generative cell zone) of normal gastric mucosa. With progression of atrophic gastritis, the generative cell zone shifts downward and a relatively large number of apoptotic cells occur. In intestinalized glands, both apoptotic cells and proliferative cells are present in deeper portions of the glands, corresponding to the generative zone. A higher frequency of apoptosis has been observed in gastric dysplasia than in coexisting gastric carcinomas, whereas the number of proliferative cells is significantly higher in gastric carcinoma than in dysplasia. Upregulation of oncogene bcl-2 in premalignant lesions and "downregulation" of the gene after malignant change is probably a common event. Accumulation of p53 protein is first detected in dysplasia, although mutation of the pS3 gene may occur in intestinal metaplasia. H. pylori infection induces apoptosis in gastric epithelial cells, which returns to normal after eradication of the infection. Numerous molecules produced by H. pylori including cytotoxin (VacA), lipopolysaccharide, monochloramine, and nitric oxide may directly induce apoptosis. Moreover, H. pylori-stimulated host inflammatory/immune responses lead to release of a large amount of cytokines. Cytokines produced by type 1 T helper cells, such as TNF-alpha and IFN-gamma, markedly potentiate apoptosis. Gastric cell proliferation is significantly higher in patients with H. pylori infection than in normal controls, and eradication of the infection leads to a reduction in cell proliferation. Apoptosis and cell proliferation are also increased in precancerous lesions such as gastric atrophy, intestinal metaplasia, and dysplasia in the presence of H. pylori infection. However, H. pylori-induced apoptosis may no longer be cell cycle-dependent in these lesions because of the occurrence of alterations and mutations of apoptosis-regulating genes, resulting in a loss of balance between apoptosis and cell proliferation. CONCLUSIONS: It is hypothesized that H. pylori-induced apoptosis may play a key role in gastric carcinogenesis by increasing cell proliferation and/or resulting in gastric atrophy. PMID- 11197248 TI - The incidence and clinical characteristics of symptomatic propylthiouracil induced hepatic injury in patients with hyperthyroidism: a single-center retrospective study. AB - OBJECTIVES: Although symptomatic propylthiouracil (PTU)-induced hepatic injury is known to be rare, there have been few reports about its exact incidence in patients with hyperthyroidism. We tried to evaluate its incidence in a single center and its clinical course. METHODS: Medical records of 912 hyperthyroid patients who had been diagnosed between March 1990 and December 1998 were reviewed about clinical characteristics, management, and laboratory findings. Symptomatic PTU-induced hepatic injury was defined as the development of jaundice or hepatitis symptoms with at least a 3-times elevation of liver function tests (LFT) without other causes. RESULTS: Four hundred ninety-seven patients (age 42.6 +/- 10.7 yr, male/female 140/357) were included. Clinically overt hepatitis developed in six patients (1.2%; age, 43.7 +/- 14.8 yr; male:female ratio, 3:3) between 12 and 49 days after PTU administration. Jaundice and itching developed in five patients, fever in two, rash in two, and arthralgia in one. Bilirubin, ALT, and ALP increased in five, four, and six patients, respectively (293 +/- 288 micromol/L, 143 +/- 111 U/L, and 265 +/- 81 U/L; normal, < 117 U/L). The type of hepatic injury was cholestatic in three, hepatocellular in one, and mixed in two patients. None resulted from viral hepatitis. There were no statistical differences in age, sex, PTU dose, or T4 and T3 levels at initial diagnosis between patients with and without hepatic injury. LFT normalized in all patients between 16 and 145 (72.8 +/- 46.4) days after the PTU withdrawal. CONCLUSIONS: Symptomatic hepatic injury develops usually within the first few months of PTU administration with rare frequency, but its clinical course is relatively benign once the drug is withdrawn. However, it may be difficult to predict its development, so all patients should be monitored for rise in LFTs at regular intervals, especially during the early period. PMID- 11197249 TI - Comorbidities and quality of life in patients with interferon-refractory chronic hepatitis C. AB - OBJECTIVES: Patients with chronic hepatitis C (HCV) consistently report a reduction in multiple domains of health-related quality of life (HRQOL) that does not correlate with liver disease severity. This may in part be due to the use of insensitive HRQOL instruments or extrahepatic factors that independently influence HRQOL. We hypothesized that a past history of substance abuse or active medical and psychiatric comorbidities would correlate with HRQOL scores. METHODS: In 107 patients who had failed previous interferon therapy, HRQOL was measured by using the modified SF-36, a disease-specific instrument, and the Health Utilities Index (HUI) Mark III, a generic instrument. RESULTS: Multiple SF-36 subscale and summary scores as well as the HUI Mark III attributes of emotion and pain were significantly reduced in the study population compared with healthy controls (p < 0.001). Serum alanine aminotransferase and HCV RNA levels, HCV genotype, liver histology, and HCV risk factors as well as demographic variables did not correlate with modified SF-36 and HUI scores. In addition, a history of alcohol abuse or dependency and intravenous drug use or dependency, identified in 52 and 51% of participants, respectively, did not correlate with HRQOL scores. However, the presence of one or more active medical comorbidities, defined as a chronic medical condition requiring treatment and monitoring, was significantly associated with both the modified SF-36 scores and HUI attribute deficits (p < 0.001). In particular, painful medical comorbidities or depressed mood requiring treatment were significantly associated with modified SF-36 scores and with HUI attribute deficits and utility scores (p < 0.001). CONCLUSIONS: Active medical and psychiatric comorbidities may account for some of the reduction and variability in HRQOL scores in patients with chronic HCV who have failed previous interferon therapy. Future studies that control for the presence of active comorbidities in large groups of treatment naive patients with varying severity of chronic HCV are needed to confirm these findings. PMID- 11197250 TI - Hepatocellular carcinoma in HIV-infected patients with chronic hepatitis C. AB - OBJECTIVES: Chronic hepatitis C is frequently seen in HIV-positive subjects infected through needle sharing or transfusion of contaminated blood products. Progression to end-stage liver disease seems to occur faster in these patients. As the life expectancy of HIV-infected persons has dramatically improved since the introduction of highly active antiretroviral therapies, cirrhosis and eventually hepatocellular carcinoma (HCC) may be recognized at an increasing rate in patients coinfected with HIV and hepatitis C virus (HCV). METHODS: We identified the main features of HIV-infected individuals with end-stage liver disease due to HCV infection and diagnosed with HCC in three HIV/AIDS referral centers, and compared these features to those of a control group of patients with HCV-related HCC but without HIV infection. RESULTS: Seven HIV-infected patients were identified. Of these, six were <45 yr of age and had been intravenous drug users. The mean time between exposure to HCV and the development of HCC was estimated to be 17.8 yr. Two subjects were coinfected with hepatitis B and delta viruses, respectively. Only one individual had been diagnosed of an AIDS-defining condition before the diagnosis of HCC was made. However, all subjects had < 500 CD4+ T cells at the time of HCC diagnosis. Five died within the first 4 months of follow-up. Patients in the control group (n = 31) were significantly older (68.9 +/- 8.9 vs 42.2 +/- 10.4; p < 0.001) and the duration of HCV infection was significantly longer (28.1 +/- 10.9 vs 17.8 +/- 2.7; p < 0.05) than in those with HIV-HCV coinfection. CONCLUSIONS: HCC seems to occur at a younger age and after a shorter period of HCV infection in subjects coinfected with HIV. Thus, treatment of CHC should be encouraged in HIV-positive patients, and in those with HCV related cirrhosis the periodic monitoring of alpha-fetoprotein and abdominal ultrasonography should be recommended. PMID- 11197251 TI - Effects of folate supplementation on two provisional molecular markers of colon cancer: a prospective, randomized trial. AB - OBJECTIVES: Dietary folate intake is inversely associated with the risk of colorectal cancer. This study investigated the effect of folate supplementation on genomic DNA methylation and DNA strand breaks in exons 5-8 of the p53 gene of the colonic mucosa, two provisional biomarkers of colon cancer. METHODS: Twenty subjects with adenomas were randomized to receive either folate (5 mg/day) or placebo for 1 yr after polypectomy. At baseline, 6 months and 1 yr, systemic and colonic measures of folate status were determined, as were the biomarkers mentioned earlier. RESULTS: Folate supplementation increased serum, red blood cell and colonic mucosal folate concentrations (p < 0.02). Folate supplementation also increased the extent of genomic DNA methylation at 6 months and 1 yr (p = 0.001), whereas placebo administration was associated with an increase in the extent of genomic DNA methylation only at 1 yr. Similarly, folate supplementation decreased the extent of p53 strand breaks in exons 5-8 at 6 months and 1 yr (p < 0.02), whereas placebo administration was associated with a decrease in the extent of p53 strand breaks only at 1 yr. CONCLUSIONS: Both of these provisional biomarkers of colon cancer underwent accelerated improvement at 6 months with folate supplementation. However, these markers also improved with placebo at 1 yr. Therefore, potential confounding factors that seem to modulate these biomarkers need to be identified and corrected in order for these markers to serve as suitable surrogate endpoints in folate chemoprevention trials. PMID- 11197252 TI - Factors that influence the decision to do an adequate evaluation of a patient with a positive stool for occult blood. AB - OBJECTIVE: The factors that influence the decision to do an adequate evaluation for a positive test for fecal occult blood in a middle-aged or elderly patient are largely unknown. Our study was undertaken to determine whether factors such as the number of positive Hemoccult II card windows, age, gender, family history of colon cancer, the patient's concern that he or she might have colon cancer, or history of rectal bleeding influence the evaluation performed. METHOD: A mass screening program for colon cancer was performed using unrehydrated Hemoccult II cards in the Boston area. RESULTS: Among the 23,593 Hemoccult II cards returned to Beth Israel Deaconess Medical Center, cards from 1,112 patients (4.7%) were found to be positive for one or more of the six possible card windows. Ninety percent, or 940 patients, over 40 yr of age had follow-up information available. As the number of positive windows increased from one to four, there was a significant trend (p < 0.001) for the adequacy of the evaluation to increase. Family history (p = 0.044) and a patient's worry that he or she might have colon cancer (p = 0.003) significantly improved a patient's chance for an adequate evaluation. CONCLUSIONS: Hemoccult testing is not followed by an adequate evaluation in a significant proportion of patients. Our study points out for the first time that the number of positive Hemoccult windows significantly influences the decision-making. PMID- 11197253 TI - Ethnic differences in colorectal cancer among Arab and Jewish neighbors in Israel. AB - OBJECTIVES: Migrant studies indicate that the differences in the incidence of colorectal cancer (CRC) are probably environmental and not genetic. There is epidemiological documentation that Israeli-born Arabs have much less CRC than Israeli-born Jews. We investigated these differences among Jews and Arabs living within the same central coastal region in Israel. METHODS: The files of pathology diagnosed patients with CRC hospitalized from 1988 to 1996 were reviewed, and demographic data and incidence and location of malignancies were retrieved for this relative frequency study. RESULTS: Of the 527 patients (51.4% men) diagnosed as having CRC, 489 (92.8%) were Jews and 38 (7.2%) were Arabs (p < 0.001), representing 0.46% and 0.04% of the respective populations in the region. The average age at disease diagnosis of the Jews was 73.8 yr and that of the Arabs 61.4 yr (p < 0.001). Both groups shared identical health facilities and habits of attending them. The Arab patients were or had been employed in occupations that involved more physical activity. The site of lesion was on the right colon in 24.9% of all the cases-23.5% of the Jewish patients and 42.1% of the Arab patients (p < 0.001). Rectal cancer was found in 25.7% of the former and 15.8% of the latter (p < 0.001). CONCLUSIONS: The lower incidence of CRC among the Arabs persisted over time, and that group had greater right side and lesser rectal involvement than their Jewish neighbors, possible indications of genicity. The incidence of CRC among the Jews rose concomitantly with "Westernization" of their lifestyle, supporting a role for environmental influences. PMID- 11197254 TI - Managing patients with acute, nonvariceal gastrointestinal hemorrhage: development and effectiveness of a clinical care pathway. AB - OBJECTIVES: To develop a clinical care pathway for the management of patients with acute upper or lower nonvariceal GI hemorrhage (GIH) who do not require immediate surgical intervention. To test the effectiveness and safety of the pathway in improving the efficiency of care for patients with acute GIH. METHODS: A multidisciplinary team developed the evidence-based GIH clinical care pathway by consensus techniques. In a quasiexperimental design, pathway outcomes were measured prospectively during the first 8 months of pathway implementation, and compared to similar time periods in the 2 prior yr. Effectiveness measures were the number of patients <65 yr of age admitted for GIH and the hospital length of stay for all patients. Thirty-day safety outcomes were the rates of recurrent GIH, mortality, and readmission to hospital for any reason. RESULTS: Of 368 patients studied after pathway implementation, 81 (22%) were managed as outpatients. The number of admissions for pathway patients <65 yr of age was significantly lower compared to 691 prepathway patients (p < 0.002). Mean length of stay (+/- 95% CI) for pathway inpatients was 3.5 (3.1, 3.9) days, compared to 5.3 (4.9, 5.7) and 4.6 (4.2, 5) days in the 2 prepathway yr, respectively (p < 0.001). Multivariable regression controlling for admission vital signs, comorbid conditions, age, and the etiology of GIH confirmed that admission after pathway implementation was an independent predictor of a reduced length of hospital stay. There were no significant between-year differences in the 30-day rates of recurrent GIH, mortality, or hospital readmission. CONCLUSION: A multidisciplinary clinical care pathway may improve the efficiency of caring for patients with acute upper or lower nonvariceal GIH. Decreasing the number of admissions for GIH and reducing the hospital length of stay can be achieved without increasing the number of adverse outcomes. PMID- 11197255 TI - Drug jars. PMID- 11197256 TI - Progressive gastrointestinal histoplasmosis leading to colonic obstruction two years after initial presentation. AB - A 37-yr-old man from Ecuador presented with abdominal pain, diarrhea, and weight loss. Endoscopy revealed duodenal histoplasmosis. The patient improved with antifungal therapy but was readmitted 2 yr later with diarrhea and fever. Colonoscopy revealed histoplasmosis lesions, including a constricting transverse colon lesion. The patient refused surgery and died of colonic perforation. We discuss the diagnosis and management of gastrointestinal histoplasmosis in this report. PMID- 11197257 TI - Marked gastric foveolar hyperplasia associated with active cytomegalovirus infection. AB - Transient protein-losing gastropathy with marked gastric rugal hypertrophy, a Menetrier's disease-like process, is an uncommon condition of unknown etiology. Most of these cases have been reported in pediatric patients; the clinical course is usually favorable. Cytomegalovirus infection has been implicated as a possible etiology in many of the reported cases. This type of Menetrier's-like disease has not been well documented in adult patients. We describe here an elderly man who presented with severe protein-losing gastropathy and large polypoid nodules in the stomach. Gastric mucosal biopsies revealed marked gastric foveolar hyperplasia with morphological evidence of cytomegalovirus (CMV) infection. Immunohistochemical analysis demonstrated an aberrant topographic distribution of staining for transforming growth factor-alpha and transforming growth factor-beta receptor II, as described in other cases of Menetrier's disease in the literature. This transient Menetrier's-like disease associated with CMV infection should be considered in the differential of both pediatric and adult patients with GI protein loss. PMID- 11197258 TI - Primary hepatic anaplastic large-cell lymphoma of T-cell phenotype in acquired immunodeficiency syndrome: a report of an autopsy case and review of the literature. AB - Anaplastic large-cell lymphomas (ALCL) were first described by Stein et al. in 1985 as large-cell neoplasms with a pleomorphic appearance, subtotal effacement of the lymph node structure, and expression of the lymphoid activation antigen CD 30 (Ki-l). Since their first description, these tumors have been documented in a variety of extranodal sites. We report a primary hepatic anaplastic large-cell lymphoma in a patient with advanced AIDS, who presented with hepatic failure and multiple nodules in the liver. A complete autopsy showed discrete tumor nodules throughout the entire liver without gross or microscopic involvement of lymph nodes or any other organs by the neoplastic process. The tumor cells showed typical histological and immunohistochemical features of ALCL and were strongly immunoreactive with the T-cell markers CD-3 and UCHL-1. Only one previous case of primary hepatic ALCL has been reported in the literature, and this tumor occurred in an immunocompetent patient and was not immunoreactive for B- or T-cell markers. To our knowledge, this study represents the first reported case of primary hepatic anaplastic large-cell lymphoma of T-cell phenotype. Additionally, this is the first case of primary hepatic ALCL reported in an AIDS patient. PMID- 11197259 TI - Delayed fatal hemorrhage from pseudoaneurysm of the hepatic artery after percutaneous liver biopsy. AB - Hemorrhage is the most common serious complication of percutaneous liver biopsy. Liver biopsy is usually done in an outpatient setting because most significant hemorrhage is evident within a few hours after biopsy. Delayed hemorrhage occurs much less frequently but carries a much higher mortality. We present a 41-yr-old man with chronic hepatitis C who underwent a percutaneous liver biopsy uneventfully but was found to have a pseudoaneurysm of the hepatic artery 5 days later. Shortly after admission, the patient experienced bleeding into the liver from the pseudoaneurysm, which was controlled initially by angiographic embolization. However, recurrent bleeding could not be controlled by repeat angiography and surgical intervention, and the patient expired. The diagnosis and management of pseudoaneurysm of the hepatic artery complicating liver biopsy is reviewed. PMID- 11197260 TI - Aggressive multiple myeloma presenting as mesenteric panniculitis. AB - Mesenteric panniculitis is a rare disease of the bowel mesentery, characterized by tumor-like infiltration by chronic inflammatory cells, fat necrosis, and fibrosis. Reported cases cited clinical presentation ranging from abdominal pain to fever of unknown origin, the majority of which were idiopathic and associated with a benign prognosis. We report the case of a 43-yr-old male who presented with malaise, weight loss, microcytic anemia, and a high erythrocyte sedimentation rate. Radiographic and histological investigations revealed typical features of mesenteric panniculitis. Initial treatment with high-dose oral prednisolone led to rapid and complete resolution of symptomatology, radiographic, and laboratory anomalies. Within 6 months, the patient presented again with anemia, renal failure, and hypercalcemia. A diagnosis of IgA kappa chain myeloma was made. Despite chemotherapy and restoration of normocalcemia, he died from refractory pulmonary edema. This is the first report of a hematological malignancy initially presenting with features of mesenteric panniculitis culminating in an aggressive course and a fatal outcome. PMID- 11197261 TI - Angiodysplasia of the appendix. AB - Angiodysplasia of the gastrointestinal tract is thought to be one of the most common causes of lower gastrointestinal bleeding in the elderly, and, in the majority of cases, lesions are located in the cecum or ascending colon. The authors report an extremely rare case of appendicular angiodysplasia. A 76-yr-old woman was hospitalized with massive recurrent red anal bleeding. Selective superior mesenteric arteriography revealed an extravasation of contrast material from the appendicular artery, and this finding proved to be bleeding from an angiodysplasia of the appendix. An appendectomy was performed, and anal bleeding did not recur postoperatively. A review of the literature revealed this to be an extremely rare case of angiodysplasia. PMID- 11197262 TI - Qua Vadis. PMID- 11197263 TI - Some of what glitters may be gold. PMID- 11197264 TI - Can postoperative relapse of Crohn's disease be prevented? PMID- 11197265 TI - Re: Saunders et al.--High mortality rate after percutaneous endoscopic gastrostomy in patients with dementia. PMID- 11197266 TI - WAGR syndrome in a baby--the result of 6-MP treatment in a father affected by Crohn's disease? PMID- 11197267 TI - Further evidence that 6-MP taken by the father with IBD provides risk of congenital anomaly to the pregnancy. PMID- 11197268 TI - Anti-Saccharomyces cerevisiae antibodies in autoimmune liver disease. PMID- 11197269 TI - Re. Zuckerman et al.--Sensitivity of CA-125 in patients with liver cirrhosis in the presence of ascites. PMID- 11197270 TI - Absence of toxicity of ornidazole after a 10-yr continous daily use for Crohn's disease. PMID- 11197271 TI - Partial obstruction of the colon caused by postoperative adhesions after cholecystectomy as a rare form of postcholecystectomy syndrome. PMID- 11197272 TI - Recurrent supraventricular extrasystolia due to retrocardiac stomach. PMID- 11197273 TI - A case of pancreatic cancer with production of granulocyte colony-stimulating factor. PMID- 11197274 TI - A nematode (ascaris) recognized by enteroclysis: a rare reason for chronic diarrhea. PMID- 11197275 TI - Enterolith-induced perforation in small bowel carcinoid tumor. PMID- 11197276 TI - Cytomegalovirus hepatitis in a nontransplant patient with autoimmune hepatitis taking immunosuppressants. PMID- 11197277 TI - Gallbladder carcinoma complicating Crohn's disease. PMID- 11197278 TI - Routine endoscopic "marking" of Dieulafoy-like lesions. PMID- 11197279 TI - Acute liver failure during lamivudine treatment in a hepatitis B cirrhotic patient. PMID- 11197280 TI - Mesenteric arteriovenous fistula causing jejunal varices and recurrent GI bleeding. PMID- 11197281 TI - Percutaneous endoscopic gastrostomy in patients with dementia. PMID- 11197282 TI - Esomeprazole once daily for 6 months is effective therapy for maintaining healed erosive esophagitis and for controlling gastroesophageal reflux disease symptoms: a randomized, double-blind, placebo-controlled study of efficacy and safety. AB - OBJECTIVE: Esomeprazole, the S-isomer of omeprazole, achieves a significantly greater healing rate and symptom resolution of erosive esophagitis than that achieved by omeprazole. The objective of this study is to assess the efficacy of the new proton pump inhibitor esomeprazole in preventing relapse over a prolonged period in patients with healed erosive esophagitis. METHODS: A total of 318 gastroesophageal reflux patients whose erosive esophagitis was healed in a comparative study of esomeprazole 40 mg, 20 mg, or omeprazole 20 mg, were randomized to maintenance therapy with once daily esomeprazole 40 mg, 20 mg, or 10 mg, or placebo in a U.S., double-blind multicenter trial. RESULTS: After 6 months, healing was maintained (cumulative life table rates) in 93.6% (95% CI 87.4-99.7) of patients treated with esomeprazole 40 mg, 93.2% (95% CI 87.4-99.0) treated with esomeprazole 20 mg, and 57.1% (95% CI 45.2-69) treated with esomeprazole 10 mg; p < 0.001 vs placebo (29.1%; 95% CI 17.7-40.3). Of patients relapsing, mean time to first recurrence of esophagitis increased with dose, from 34 days (placebo) to 78 days (10 mg), 115 days (20 mg), and 163 days (40 mg). Patients treated with esomeprazole had less frequent and less severe heartburn than those treated with placebo. At month 6, more than 70% of patients being treated with esomeprazole remained symptom-free. CONCLUSIONS: Esomeprazole is effective and well tolerated in the maintenance of a healing erosive esophagitis. Esomeprazole 40 mg and 20 mg maintain healing in over 90% of patients while providing effective control of heartburn symptoms. PMID- 11197283 TI - Treating chronic Hepatitis C patients with psychiatric disorders: an uphill battle. PMID- 11197284 TI - Effect of age on differences in upper esophageal sphincter and pharynx pressures between patients with dysphagia and control subjects. AB - OBJECTIVES: The aim of this study was to explore the effect of age and food consistency on manometric data of the swallow sequence in patients with dysphagia. METHODS: Manometric data from 41 patients (age range, 32-88 yr) and 41 age-matched control subjects was examined for differences between subgroups < 60 yr and > or = 60 yr of age, as well as for changes with food consistency. RESULTS: Only pharynx peak pressure showed an age-dependent decrease (144.1 +/- 21.4 mm Hg vs 95.8 +/- 15.1 mm Hg, p < 0.05) in patients. Significant higher upper esophageal sphincter residual pressure and delayed onset of upper esophageal sphincter relaxation were noted in patients aged <60 yr compared to age-matched controls, whereas only pharynx peak pressure was significantly lower in patients compared to controls aged > or = 60 yr. Food consistency did not have a consistent effect on manometric results in patients with dysphagia. CONCLUSIONS: This is the first study to systematically explore the influence of age and food consistency on manometric parameters in dysphagia patients. These results may provide useful insights when identifying actual manometric abnormalities in patients with dysphagia. They also suggest possible different underlying mechanisms of dysphagia in younger versus older patients. PMID- 11197285 TI - Risk factors for erosive reflux esophagitis: a case-control study. AB - OBJECTIVES: It is presently not fully understood which risk factors contribute to the occurrence of reflux esophagitis and how such factors might influence the severity of the disease. The aim of this study was to delineate the clinical epidemiology of erosive reflux esophagitis. METHODS: Outpatients from a medicine and gastroenterology clinic who underwent upper GI endoscopy were recruited into a case-control study. A total of 1,533 patients with and 3,428 patients without endoscopically diagnosed reflux esophagitis were categorized as case and control subjects, respectively. Using multivariate logistic regressions for statistical analysis, the presence of esophageal erosions, ulcers or strictures, served as three separate outcome variables. Demographic characteristics, intake of nonsteroidal anti-inflammatory drugs (NSAIDs), consumption of alcohol and cigarettes, and the presence of hiatus hernia or peptic ulcer served as predictor variables. RESULTS: Erosive reflux esophagitis tended to occur more frequently in Caucasian male patients. Hiatus hernia was associated with a strong risk for developing esophageal erosions, ulcers, and strictures. Although statistical significance was demonstrated only for esophageal erosions, in all grades of reflux esophagitis alike, gastric and duodenal ulcer exerted a protective influence. Consumption of NSAIDs increased the risk for esophageal ulcers only. Smoking and alcohol were not associated with an increased risk of developing any type of erosive reflux esophagitis. CONCLUSIONS: The results stress the critical role played by hiatus hernia in all grades of erosive reflux esophagitis. NSAIDs may act through a mechanism of topically induced esophageal injury. Our data also suggest that the presence of either gastric or duodenal ulcer exerts a protective influence against the development of reflux disease. PMID- 11197286 TI - Bleeding reflux esophagitis: a prospective 1-year study in a university hospital. AB - OBJECTIVES: The prevalence of bleeding from reflux esophagitis has not been studied. The aim of the study was to evaluate the 1-yr prevalence of bleeding from reflux esophagitis, as well as the independent factors associated with bleeding. METHODS: All patients with reflux esophagitis diagnosed with upper digestive tract endoscopy in Reims Hospital in 1996 were included. Studied parameters were prospectively recorded and compared between patients with bleeding and nonbleeding reflux esophagitis. RESULTS: Endoscopy was performed in 1983 patients of whom 219 (11.0%) had overt upper digestive tract hemorrhage. Reflux esophagitis was the cause of bleeding in 32 patients (14.6%). Reflux esophagitis was diagnosed in 391 patients during the same period of time. Bleeding reflux esophagitis accounted for 8.2% of them. Independent factors associated with bleeding were grade 3 or 4 (Savary-Miller) esophagitis (odds ratio [OR]: 25.5, 95% confidence interval [CI]: 9.6-67.9), cirrhosis (OR: 5.7, 95% CI: 1.7-18.9), Eastern Cooperative Oncology Group performance status > or = 3 (OR: 4.6, 95% CI: 1.5-14.2), and anticoagulant therapy (OR: 3.9, 95% CI: 1.2 12.5). A history of reflux esophagitis or heartburn was noted in only 28.1% or 37.5% of the patients with bleeding reflux esophagitis, respectively. CONCLUSIONS: In this population of patients with reflux esophagitis, the prevalence of bleeding esophagitis was high (8.2%). Bleeding esophagitis occurred primarily in patients with severe esophagitis and was the revealing clinical form of gastroesophageal reflux disease in the majority of cases, suggesting that bleeding prevention would hardly be effective. PMID- 11197287 TI - Initial validation of a diagnostic questionnaire for gastroesophageal reflux disease. AB - OBJECTIVES: Brief, reliable, and valid self-administered questionnaires could facilitate the diagnosis of gastroesophageal reflux disease in primary care. We report the development and validation of such an instrument. METHODS: Content validity was informed by literature review, expert opinion, and cognitive interviewing of 50 patients resulting in a 22-item survey. For psychometric analyses, primary care patients completed the new questionnaire at enrollment and at intervals ranging from 3 days to 3 wk. Multitrait scaling, test-retest reliability, and responsiveness were assessed. Predictive validity analyses of all scales and items used specialty physician diagnosis as the "gold standard." RESULTS: Iterative factor analyses yielded three scales of four items each including heartburn, acid regurgitation, and dyspepsia. Multitrait scaling criteria including internal consistency, item interval consistency, and item discrimination were 100% satisfied. Test-retest reliability was high in those reporting stable symptoms. Scale scores significantly changed in those reporting a global change. Regressing specialty physician diagnosis on the three scales revealed significant effects for two scales (heartburn and regurgitation). Combining the two significant scales enhanced the strength of the model. Symptom response to self-directed treatment with nonprescription antisecretory medications was highly predictive of the diagnosis also, although the item demonstrated poor validity and reliability. CONCLUSIONS: A brief, simple 12-item questionnaire demonstrated validity and reliability and seemed to be responsive to change for reflux and dyspeptic symptoms. PMID- 11197288 TI - Randomized study of two "rescue" therapies for Helicobacter pylori-infected patients after failure of standard triple therapies. AB - OBJECTIVES: A novel rifabutin-based therapy is able to cure Helicobacter pylori infection in most patients who have failed eradication after standard proton pump inhibitor (PPI)-based triple therapy. We compared this regimen with the quadruple therapy. METHODS: A total of 135 patients were randomized into three groups who were treated for 10 days with pantoprazole 40 mg b.i.d., amoxycillin 1 g b.i.d., and rifabutin 150 mg o.d. (RAP50150 group), or 300 mg o.d. (RAP300 group), and pantoprazole 40 mg b.i.d., metronidazole 250 mg t.i.d., bismuth citrate 240 mg b.i.d., and tetracycline 500 mg q.i.d. (QT group). Before therapy, patients underwent endoscopy with biopsies for histology, culture and antibiotic susceptibility tests. H. pylori eradication was assessed by the 13C-urea breath test. RESULTS: On intention-to-treat analysis, eradication rates (with 95% confidence intervals [CI]) were 66.6% (53-80%) in the RAP150 and QT groups, respectively, and 86.6% (76-96%) in RAP300 group (p < 0.025). Most patients harboring metronidazole- and clarithromycin-resistant strains were eradicated at an equal rate by each of the three regimens. Side effects were observed in 9% and 11% of rifabutin-treated patients, and in 47% of those on quadruple therapy (p < 0.0001). CONCLUSIONS: In patients who failed standard eradicating treatments, a 10-day course of rifabutin with pantoprazole and amoxycillin is more effective and well tolerated than the quadruple therapy. PMID- 11197289 TI - Associations of food-cobalamin malabsorption with ethnic origin, age, Helicobacter pylori infection, and serum markers of gastritis. AB - OBJECTIVES: Food-cobalamin malabsorption is common in patients with low cobalamin levels. However, characterization of affected subjects has been limited. The aim of this study was to analyze demographic and gastric data in a large study population. METHODS: Data were collected prospectively in 202 subjects (43 volunteers and 159 patients) who underwent the egg yolk-cobalamin absorption test (EYCAT). H. pylori status was determined in 167 of the subjects, serum gastrin and antiparietal cell antibody in 158 and pepsinogen (PG) I and PG II levels in 133. RESULTS: Latin American and black patients had lower EYCAT results than did white or Asian-American ones (p = 0.0001) and had severe food-cobalamin malabsorption (EYCAT < 1%) more often (p = 0.0001). Age correlated inversely with EYCAT results (p = 0.02). H. pylori infection was associated with food-cobalamin malabsorption (p = 0.0001), especially with severe malabsorption where 29/37 subjects (78.4%) were infected. Malabsorption was also associated with higher gastrin levels (p = 0.0001) and lower PG I levels (p = 0.01) and PG I:PG II ratios (p = 0.0001). Multivariate analysis showed that ethnic origin, gastrin levels, H. pylori infection and, to a lesser extent, age were independently associated with the EYCAT results. CONCLUSIONS: Latin American and black patients have food-cobalamin malabsorption more often than do white and Asian-American patients. This association is independent of the malabsorption's association with H. pylori infection, markers of gastritis, such as gastrin, and older age. The patterns of gastric tests suggest that malabsorption may be due to diverse mechanisms, not just atrophic gastritis. The possible role of H. pylori infection in many cases of severe food-cobalamin malabsorption also suggests avenues of treatment and prevention. PMID- 11197290 TI - Impact of chronic gastrointestinal symptoms in diabetes mellitus on health related quality of life. AB - OBJECTIVES: Morbidity from GI symptoms in diabetes is considered to be high, but no studies have quantified the impact of GI symptoms in diabetes on health related quality of life. We hypothesized that diabetics reporting increased GI symptoms would experience more impaired quality of life. METHODS: Subjects from the community with diabetes (n = 892) and outpatients with diabetes (n = 209) were recruited for this study. Subjects were divided into type 1 (diabetes diagnosed at age <30 yr and requiring insulin) and type 2. A validated questionnaire measuring GI symptoms and diabetes status and the Short Form-36 were completed. The results were compared with Australian normal data. GI symptom groups measured were frequent abdominal pain, bowel-related abdominal pain, reflux, dyspepsia, constipation, diarrhea, and fecal incontinence. RESULTS: There was a clinically significant decrease in quality-of-life scores in diabetics compared with population norms across all subscales. The impact on quality of life in diabetes was predominantly observed in type 2 diabetics. The quality-of life scores in all subscales decreased markedly with increasing numbers of distinct GI symptom groups, and this was similar in community and outpatient diabetics. For all the Short Form-36 subscales, GI symptom groups were significantly (all p < 0.0001) associated with poorer quality of life in diabetes, independent of age, gender, smoking, alcohol use, and type of diabetes. CONCLUSIONS: GI symptoms impact negatively on health-related quality of life in diabetes mellitus. PMID- 11197291 TI - Gastric involvement in systemic sclerosis: a prospective study. AB - OBJECTIVES: This study aims to assess the prevalence of gastric electrical activity dysfunction with cutaneous electrogastrography (EGG), disturbances of gastric emptying function using radiopaque pellets, and gastric endoscopic abnormalities in patients with systemic sclerosis (SSc). We also investigate for an association between EGG and gastric-emptying data with clinical manifestations and esophageal motor disturbances. METHODS: Fasting and postprandial gastric electrical activity was studied in 22 consecutive patients with SSc (17 with and 5 without clinical gastric manifestations) and 22 age- and sex-matched healthy subjects. Gastric emptying of radiopaque pellets and gastroscopy were also performed in SSc patients. RESULTS: The prevalence of EGG disturbances was as high as 81.82% in SSc patients. SSc patients exhibited, compared with controls, higher median percentage of dominant frequency in bradygastria during the fasting period and lower median values for postprandial electrical power and postprandial to fasting ratio for electrical power. Gastric emptying of radiopaque pellets was delayed in 11 SSc patients, and gastroscopy demonstrated "watermelon stomach" in 3 SSc patients. No correlation was found between the severity of gastric impairment and clinical presentation, SSc duration and subsets, and esophageal manometric impairment. CONCLUSIONS: Our study underlines the high frequency of gastric dysfunction in SSc patients. It suggests the usefulness of EGG in SSc in noninvasively detecting disorders of gastric electrical activity at an early stage and symptomatic patients with gastroparesis (because there was a correlation between values of postprandial to fasting ratio for electrical power of < 1 on EGG and delayed gastric emptying). Gastric-emptying evaluation of radiopaque pellets may further be a helpful method to depict symptomatic SSc patients with gastroparesis. Finally, our series confirms that watermelon stomach diagnosis should be excluded in SSc patients presenting with gastrointestinal hemorrhage or with anemia related to iron deficiency. PMID- 11197292 TI - Genetic and familial considerations of primary biliary cirrhosis. AB - The genetic basis of human autoimmune diseases is receiving increasing attention. Primary biliary cirrhosis (PBC) is a model autoimmune disease reflective of other organ-specific autoimmune pathology. PBC is an enigmatic autoimmune disease that predominantly affects women and leads to destruction of intrahepatic bile ducts. The serological hallmark of this disease is characterized by antimitochondrial antibodies that specifically react with the E2 components of 2-oxodehydrogenase enzymes, including PDC-E2. There are no clear major histocompatibility complex associations with the development of PBC, despite the observation that first degree relations of index patients with PBC have a 4-6% prevalence of development of PBC. This risk factor is comparable or higher than any other human autoimmune disease and suggests that a genome-wide approach towards dissection of genetic associations would lead to valuable new insights. In this review, we place these concepts in perspective and highlight in particular the genetic associations in PBC and the importance of studying siblings with PBC who are concordant for disease. PMID- 11197293 TI - Seroprevalence of Helicobacter pylori in patients with colorectal polyps and colorectal carcinoma. AB - OBJECTIVES: The role of Helicobacter pylori in the pathogenesis of colorectal polyps and colorectal carcinoma is unknown. H. pylori infection causes fasting and meal stimulated hypergastrinemia. Gastrin increases colorectal mucosal proliferation and promotes tumor growth. We performed a prospective study to determine the seroprevalence of H. pylori in patients with colorectal polyps and colorectal carcinoma and in controls. METHODS: Blood samples were collected from 189 patients with colorectal carcinoma, 57 patients with colorectal polyps, and 179 controls. H. pylori serology was determined by an ELISA assay. RESULTS: Logistic regression showed no difference in seroprevalence of H. pylori between patients with colorectal cancer and controls (odds ratio, 1.1; 95% confidence interval, 0.7 to 1.8) or between patients with colorectal polyps and controls (odds ratio 1.3; 95% confidence interval, 0.7 to 2.5). Age and sex were not found to be associated with H. pylori infection. Patients in social classes IV and V were 2.3 times more likely to have H. pylori infection than those in social classes I, II, and III (95% confidence interval, 1.3 to 4.2). CONCLUSIONS: This study shows that there is no increase in the seroprevalence of H. pylori in patients with colorectal polyps or colorectal carcinoma compared with controls. These results do not support the hypothesis that there is a relationship between H. pylori infection and the development of colorectal neoplasia. PMID- 11197294 TI - Peptic ulcer bleeding: comparison of two hemostatic procedures. AB - OBJECTIVE: Bleeding is a serious complication of peptic ulcer. Endoscopic injection therapy is accepted as a homeostatic endoscopic treatment in acute nonvariceal of upper GI hemorrhages, particularly in bleeding peptic ulcers. The risk of rebleeding is predicted by the endoscopic appearance of ulcer features classified according to Forrest's criteria. METHODS: Two hundred twenty-three patients were selected from 1,003 emergency upper endoscopies for GI bleeding. According to Forrest's criteria, 99 well-matched patients with ulcers F1 and F2 were considered at risk of rebleeding; 54 patients (group A) received local ulcer injection of epinephrine solution 1:10,000, whereas (group B) patients were treated with local epinephrine injection and then with endoscopic Hemoclips. (1) We considered the control of bleeding, the number of rebleeding episodes, the need for emergency surgery, and mortality. RESULTS: Bleeding ulcers stopped completely in 83.3% group A patients, and in 95.6% group B patients (p = not significant). In a subset of F1b patients the rebleeding rate was 31 % for group A and 0% for group B (p < 0.05). There was no mortality as a result of the procedure. There was a trend toward reducing surgery in favor of the combined therapy (0% vs 7.4%). No differences were found in transfusion requirements or mean hospitalization days. CONCLUSIONS: We conclude that endoscopic injection of l:10,000 epinephrine solution alone and epinephrine solution plus application of Hemoclips are equivalent therapies in treating bleeding and rebleeding from peptic ulcers. There was no difference between therapies in terms of need for surgery or mortality. Possibly combination therapy is more effective in treating ulcers that are actively oozing. PMID- 11197295 TI - A randomized controlled trial of total colonic decompression after colonoscopy to improve patient comfort. AB - OBJECTIVES: Bloating occurring after colonoscopy may cause significant discomfort in some patients. We sought to determine whether total colonic decompression decreased bloating and improved comfort after colonoscopy. METHODS: Consecutive outpatients undergoing elective colonoscopy were randomized to total colonic decompression or to the control group after completion of the routine colonoscopy. The colonoscope was advanced again to the cecum and the air aspirated during withdrawal in patients randomized to decompression and the procedure was terminated without decompression in control patients. Pain and bloating was assessed in the recovery room and in 24-48 h using a five-point scale. RESULTS: Sixty-five patients were randomized to decompression and 61 were randomized to the control group. The baseline demographic and procedural characteristics were similar between the two groups, but decompression took significantly longer (median, 17 min vs 14 min, p = 0.0002). Seventy-five percent of the decompression group and 80% of the control group denied any pain during colonoscopy. Significantly fewer patients from the decompression group complained of bloating after the procedure (25% vs 59%, p < 0.001) when questioned in the recovery room. However, comparable patients complained of postprocedure bloating when questioned in 24-48 h after the procedure (45% of decompression group vs 47% of control group, p = 0.86). The nurse and the endoscopist were poor at predicting the patient's bloating and significantly overestimated the level of pain. CONCLUSIONS: Total colonic decompression does not significantly reduce bloating after colonoscopy when assessed 24-48 h after the procedure. PMID- 11197296 TI - [What is your diagnosis? Erythema migrans]. PMID- 11197297 TI - [Treatment of depression with St. Johns wort in general practice]. AB - 70-90% of depressive patients are treated by their own family doctors. Recognising and treating depression is an important daily problem for family doctors. The severity of the disorder decides whether non-pharmacological therapy or pharmacotherapy is preferable. The choice and dosage of an antidepressant is dictated by the severity and the symptomatology of the disorder as well as the expected adverse effects. Not least on account of their low rate of adverse effects, phytotherapeutic agents are enjoying growing popularity among patients and thus assure high compliance. The use of herbal preparations is useful, in particular for mild to moderate depression in young patients or patients with a reserved attitude toward "chemical drugs". Of all phytopharmaceuticals St.-John's wort has been most widely scientifically documented for the treatment of depression. PMID- 11197298 TI - [St. Johns wort extract as plant antidepressant]. AB - In 1998 a standardized hypericum extract has been approved in Austria and Germany for treatment of mild and moderate depression. The efficacy has been already recognized since 1984 from the German Health Authorities based on traditional knowledge. However, this has been substantiated in the subsequent years in controlled clinical trials. Twenty of these studies including a total of 1787 patients have been filed, among them ten older studies in which hypericum was extracted with ethanol compared to newer studies in which the extract was methanol (LI 160). In the past ten years several controlled clinical trials have been conducted compared with placebo as well as synthetic antidepressants. These studies have shown that the effective dosage is within a range of 600-900 mg extract. The side effects are substantially fewer than with synthetic antidepressants and range within 3%. The most important risk is photosensitization, which is however without clinical relevance in the recommended dosages. Recent pharmacological studies revealed that hypericum extracts have a similar mechanism of action like the selective serotonin reuptake inhibitors (SSRI), however, very likely to a smaller extent. PMID- 11197299 TI - [Phytotherapeutic drugs and sleep]. AB - Most of the studies about phythotherapeutics and sleep confirmed only hypnotic effects on subjective sleep variables. For LI 160, a hypericum extract, an induction of slow wave sleep was demonstrated in older volunteers. In patients with major depression (MD) an increase of slow wave sleep was observed by our group after a six week therapy with hypericum extract (LI 160) and after an adjunct therapy with Ginkgo biloba LI 1370 extract. In MD sleep disturbances and hypersecretion of glucocorticoids are common features. For LI 160 beneficial effects on depressed mood and for LI 1370 effects on cognitive functioning are well documented. The potential relationship between influence on sleep structure and the hypothalamic-pituitary-adrenal axis will be discussed within the neurophysiological-neuroendocrine "extended two process model" of sleep regulation. PMID- 11197300 TI - [Treatment of dysthymia]. AB - Hippocrates described both melancholy and dysthymia. An episode of mild depression lasting up to 2 years, which does not make patients unfit to work, although the repressive irritative mood disorder does reduce their ability to work. Severe depressive moods can develop from dysthymia. While dysthymia responds to antidepressant treatment similarly to depressive episodes, treatment must be carried out for a considerably longer period. The dosage dose not differ from that for severe depressive episodes. A few examples of cases are presented from the speaker's own cases to illustrate how well they responded to treatment with St.-John's wort. PMID- 11197301 TI - Allelic variants of human beta-chemokine receptor 5 (CCR5) promoter: evolutionary relationships and predictable associations with HIV-1 disease progression. AB - Variability in the natural history of HIV-1 infection has been repeatedly associated with genetic variants in the beta-chemokine receptor 5 (CCR5) locus. While CCR5 coding sequences have demonstrated relatively limited variation, sequences of its promoter appear polymorphic in all major populations. Our studies revealed five major CCR5 promoter alleles with distributions that differed widely among the four distinct ethnic groups from Kigali, Rwanda and Bronx, New York. In particular, promoter allele P*0103 (G59029-T59353-T59356 A59402-C59653) was largely restricted to black subjects. The promoter allele P*0202 (A59029-C59353-C59356-A59402-T59653) was tightly linked to the slightly less frequent CCR2b-641, a variant of the CCR2b gene, which is about 12.7 kbp upstream from the promoter region. Another closely related promoter allele P*0201 (A59029-C59353-C59356-A59402-C59653) exclusively carried the far less common CCR5 delta 32, a 32-bp deletion in the CCR5 coding sequence 2 kbp downstream from the promoter. The homozygous P*0201/*0201 genotype can be predicted as a risk factor for more rapid disease progression. Among human, chimpanzee, pig-tailed macaque, and sooty mangabey promoter allelic sequences, the apparent ancestral lineage of the promoter sequence (G59029-T59353-C59356-A59402-C59653 = human P*0102) was highly conserved across the primate species analyzed here while P*0201 and P*0202 arose more recently than the other three major alleles. Further effort to establish the mechanism by which CCR chemokine receptor polymorphisms govern the initiation and pathogenesis of primate lentivirus infection apparently requires fully detailed genotypic characterization of the affected populations. PMID- 11197303 TI - Cytokine gene polymorphism in human disease: on-line databases. AB - The pathologies of many infectious, autoimmune and malignant diseases are influenced by the profiles of cytokine production in pro-inflammatory (TH1) and anti-inflammatory (TH2) T cells. Interindividual differences in cytokine profiles appear to be due, at least in part, to allelic polymorphism within regulatory regions of cytokine gene. Many studies have examined the relationship between cytokine gene polymorphism, cytokine gene expression in vitro, and the susceptibility to and clinical severity of diseases. A review of the findings of these studies is presented. An on-line version featuring appropriate updates is accessible from the World Wide Web site, http://www.pam.bris.ac.uk/services/GAI/cytokine4.htm. PMID- 11197302 TI - Genetic analysis of multiplex rheumatoid arthritis families. AB - To examine the genetic contribution of HLA and non-HLA genes in the etiopathogenesis of rheumatoid arthritis (RA), 60 Caucasian multiplex families were identified and DNA analyzed for over 52 markers including DRB1, DQA1 and DQB1 alleles. Many of the markers were chosen because of close proximity to candidate genes suggested by previous studies or models of pathogenesis. Sibling pair analysis (SIBPAL), relative pair analysis (RELPAL) and linkage studies using two different models of inheritance suggested linkage for the MHC and two additional chromosomal regions: chromosome 2 (D2S443 near CD8 and IGk; 2p13 2p11.1), and chromosome 15 (CYP19-estrogen synthase; 15q15). No support was found for two chromosomal regions, 1p36 and 3q13, recently suggested by other studies. We used transmission disequilibrium testing (TDT), conditional logistic regression, and segregation analysis to study the contributions that the shared epitope and TNF-c have in contributing to risk for RA. These studies provide additional evidence that the association of HLA alleles in RA patients from multiplex families is similar to that observed in sporadic disease, suggest candidate regions for further analysis and find additional support for an association of TNF-c alleles with RA susceptibility. PMID- 11197304 TI - The interferon gene cluster: a candidate region for MS predisposition? Multiple Sclerosis Study Group. AB - The clinical benefits of interferon (IFN) beta therapy in some multiple sclerosis (MS) patients are still unexplained, raising the question whether polymorphism within the IFNB gene itself would provide an explanation. Screening the IFNB gene by single strand conformation polymorphism (SSCP) analysis and sequencing, a single nucleotide polymorphism was identified. Both alleles were distributed with similar frequencies in MS patients and controls. Significant linkage disequilibrium (LD) between the IFN allele [153C] and allele [02] of the previously analyzed IFNA microsatellite (Epplen et al. Ann Neurol 1997; 41: 341 352) was observed in MS patients only, indicating a disease related haplotype. On the other hand an increased risk (RR = 12.41; Pc < 8 x 10(-5)) was observed for allele [07]. Hence the study was extended to neighbouring genes. Functionally relevant polymorphisms, i.e., premature stop codons in the IFNA10 [Cys20Stop] and IFNA17 [58Stop] genes and an aminoacid (aa) substitution [ile 184Arg] in the IFNA17 gene were analyzed. Patients carrying a non-functional IFNA17 allele bear an increased risk to develop MS (RR = 25.68; Pc < 0.06). In addition, LD analysis between IFNA10 [Cys20Stop], IFNA17 [58Stop] and the IFNA microsatellite alleles provides evidence for IFNA14, IFNA16 or IFNA5 as additional, most likely candidate genes. The present study excludes the IFNB gene as a candidate for MS predisposition but provides first evidence for predisposing IFNA genes. PMID- 11197305 TI - Association of IL-6 gene alleles with systemic lupus erythematosus (SLE) and with elevated IL-6 expression. AB - To evaluate the association of alleles of regions having regulatory potential in the IL-6 gene, with SLE, the AT-rich minisatellite in the 3' flanking region and the 5' promoter-enhancer of the IL-6 gene were genotyped by PCR- and RFLP-based methods. The AT-rich minisatellite allele distribution pattern was significantly different in SLE (n = 146) as compared to 139 controls (chi 2(7) = 48.97, P = 0.001, Caucasians; and chi 2(7) = 19.93, P = 0.006, African-Americans). In either race, short allele sizes (< or = 792 bp) were seen exclusively in SLE patients (P = 0.001), whereas the 828-bp allele was over-represented in controls (P = 0.015 and 0.002). In contrast, there was no preferential association of SLE with G/C alleles in the 5' region of the IL-6 gene. Furthermore, our results suggest that the 3' minisatellite alleles have biological significance: (1) B lymphoblastoid cells of patients having one or two SLE-associated alleles secreted IL-6 in 3- to 4-fold higher levels than non-allelic cells (P < 0.05); (2) higher percentages (approximately 4-fold) of IL-6 positive monocytes were observed in individuals having SLE-associated IL-6 alleles; (3) in lupus patients having SLE-associated minisatellite alleles, IL-6 mRNA stability was significantly enhanced. PMID- 11197306 TI - Association of Fc gamma receptor IIIB, but not of Fc gamma receptor IIA and IIIA polymorphisms with systemic lupus erythematosus in Japanese. AB - Human Fc gamma receptor (Fc gamma R) genes form a clustered gene family on chromosome 1q21-24. Although the association of Fc gamma R polymorphisms with systemic lupus erythematosus (SLE) has been extensively studied, the results are often contradictory. In this study, Fc gamma RIIA-131H/R, Fc gamma RIIIA-176F/V and Fc gamma RIIIB-NA1/2 genotypes were determined in the Japanese patients with SLE (n = 81) or rheumatoid arthritis (RA, n = 115) as well as in healthy individuals (n = 217), and possible association with the disease was tested using case-control analysis. Unlike in other populations, significant difference was not observed in the frequencies of Fc gamma RIIA and Fc gamma RIIIA genotypes between patients with SLE and healthy individuals. However, significant difference was detected in the frequencies of Fc gamma RIIIB genotypes between SLE and healthy individuals (P = 0.008). The odds ratio [OR] of the Fc gamma RIIIB-NA2/NA2 homozygotes for the development of SLE was 2.52 (95% confidence interval [CI]: 1.33-4.79). Among the patients with SLE, individuals with NA2/2 were significantly more likely to have lupus nephritis (P = 0.007). No association was observed between any of the Fc gamma R polymorphisms and RA. Significant linkage disequilibrium was detected between Fc gamma RIIIA and IIIB, but neither between IIA and IIIA, nor between IIA and IIIB. These observations may underscore the relevance of defective immune complex handling in the pathogenesis of SLE, or may suggest the presence of primarily associated gene(s) in linkage disequilibrium with Fc gamma R genes. PMID- 11197307 TI - An IL-13 promoter polymorphism associated with increased risk of allergic asthma. AB - IL-13 plays a crucial role in the development of allergic asthma by several mechanisms, including induction of IgE antibodies, airway eosinophilia and hyper reactivity. We previously established a deregulated production of IL-13 by T cells from allergic asthma patients. In this report we describe the identification of a novel IL-13 promoter polymorphism (C to T exchange) at position -1055. The IL-13 -1055 TT genotype is associated with allergic asthma (P = 0.002), altered regulation of IL-13 production (P < 0.002), and increased binding of nuclear proteins to this region. We postulate that the presence of this polymorphism predisposes to the development of allergic asthma. PMID- 11197308 TI - Heat-shock protein (HSP70-2) allelic frequencies in three distinct Mexican populations. AB - The major histocompatibility complex (MHC) genes are highly polymorphic and therefore have been useful in population genetics and disease association studies. We analyzed restriction fragment length polymorphism of HSP70-2 alleles in healthy unrelated Mestizo, Mazatecan and Nahua populations. Both Indian groups, Mazatecans and Nahuas, were in Hardy-Weinberg equilibrium, while Mestizos were in disequilibrium (chi 2 = 0.399; P < 0.05). The Mazatecan Indians presented a high frequency of BB homozygosity (17.35%) compared to Mestizos (5%) (P = 0.01). Mexican ethnic groups present differences in distribution of BB genotype. The low frequency of BB genotype in Mestizos may be the result of a negative selection process. PMID- 11197309 TI - What's new in Nicotine & Tobacco Research? PMID- 11197310 TI - Newspaper advertising could distort research results. PMID- 11197311 TI - Correlates of youth smokeless tobacco use. AB - The objectives of this study are to identify knowledge and attitude variables that correlate with smokeless tobacco use and how youth users and non-users differ in their attitudes and knowledge about smokeless tobacco. A randomized cluster sample of 1834 total fifth, eighth, and 11th grade students in West Virginia public schools during the 1996-1997 school year were surveyed on smokeless tobacco knowledge, attitudes and practices. Data from 648 male non users and 160 male monthly and daily users of smokeless tobacco were compared using chi 2 and two-tailed t-tests. Logistic regression analysis of survey variables revealed the following correlates of smokeless tobacco use: having a family member not living in the home who uses, having a friend who uses, playing football, having tried cigarettes, and having parents who would permit use at home. Important differences exist in knowledge and attitudes regarding smokeless tobacco between users and non-users in fifth, eighth, and 11th grade West Virginia public schools. Correlates of smokeless tobacco use are identified which can be used to target prevention programs. PMID- 11197312 TI - Does smoking reduction result in reduction of biomarkers associated with harm? A pilot study using a nicotine inhaler. AB - The aim of the study was to determine if smoking reduction using a nicotine inhaler in heavy cigarette smokers who wanted to reduce but not stop smoking results in decreased levels of known biomarkers of harm. The study design was a one-sample within-subject comparative open-label study of 23 (10 male and 13 female) subjects using a nicotine inhaler to reduce smoking, with follow-up at 24 weeks. A structured protocol was used with a smoking-reduction schedule from 40 or more cigarettes per day to 10 cigarettes per day by week 9. Behavioral counseling was provided by a research assistant and ad lib use of the nicotine inhaler for 12 weeks was permitted. Blood thiocyanate, cotinine, 4-aminobiphenyl hemoglobin adducts; urine NNAL and NNAL-glucuronide; and expired air carbon monoxide were measured. On average, the subjects were able to reduce their smoking by over 50% at week 12, but only two were able to reduce to 10 cigarettes per day. The reported reduction in smoking was not associated with a consistent reduction in the biomarkers. There was no reduction in the NNAL, 4-aminobiphenyl hemoglobin adducts nor carbon monoxide levels of expired air. There was a significant reduction of NNAL-glucuronide and the sum of NNAL and NNAL glucuronide but only at week 24. Thiocyanate levels increased. Before widely promoting harm reduction as a treatment strategy for heavy smokers, more research needs to be performed to prove conclusively that such smokers who want to reduce but not stop can actually reduce and maintain their smoking rate at a level which is likely to reduce harm. It also needs to be determined whether a reduction in the smoking rate translates into reduction of harm. At the present, for heavy smokers, an abstinence approach seems to be more scientifically sound. PMID- 11197313 TI - Ethnic differences in patterns and correlates of age of initiation in a population of Air Force recruits. AB - Early age of initiation is a significant risk factor for long-term dependent smoking and may also relate to other unhealthy behaviors. The current study assessed age of initiation in relationship to smoking dependence and motivation to quit, physical activity, dietary intake, body mass index (BMI), attitude toward illegal drug use, binge drinking, seat belt use, and smoking status at follow-up. Subjects were 7995 Air Force recruits who reported smoking regularly up to Basic Military Training. Euro-Americans initiated smoking more than a year earlier on average (15.5 years) than did African-Americans (16.8 years), with Hispanic-Americans (16.0 years) between these two groups. No gender differences were found for age of initiation for any ethnic group. Early age of initiation in Euro-Americans was associated with greater dependence on tobacco, reduced motivation to quit, less likelihood of quitting in the next 12 months, and a number of other health risk factors including lower self-reported physical activity, greater intake of high-fat foods, more favorable attitudes toward illegal drugs, increased likelihood of binge drinking, and less reported use of seat belts. Relationships between early age of initiation and other unhealthy behaviors were less consistent for African-Americans and for neither African Americans nor Hispanics did age of initiation predict smoking status at 1-year follow-up. PMID- 11197314 TI - Effects of nicotine replacement therapy on markers of oxidative stress in cigarette smokers enrolled in a smoking cessation program. AB - Twenty healthy, asymptomatic long-term cigarette smokers (8 males, 12 females; mean age: 43 +/- 9 years) were selected at random from a larger series receiving nicotine replacement therapy (NRT) for 12 weeks to study the effects of NRT on plasma markers of oxidative stress. Plasma aliquots, obtained at baseline (T0) and after 12 weeks (T12) of NRT, were used to measure malondialdeyde (MDA) and total Trolox-equivalent antioxidant capacity (TEAC). In subjects who completely quit smoking ('quitters', n = 10), MDA was higher at T0 (1.08 mumol/l, interquartile range 0.85-1.16) than at T12 (0.71 mumol/l, range 0.32-0.92; p < 0.01), and TEAC was lower at T0 (1.20 mM, range 1.11-1.31) than at T12 (1.43 mM, range 1.31-1.49; p < 0.05). In subjects who had only reduced the number of cigarettes smoked per day ('reducers', n = 10), differences between the T0 and T12 levels of MDA (0.81 [0.75-0.96] vs. 0.76 [0.58-0.84] mumol/l) and TEAC (1.28 [1.05-1.50] vs. 1.25 [1.09-1.42] mM) were not significant. At T0, MDA and cotinine levels correlated in reducers (r = 0.79, p < 0.05) and, though not significantly, in quitters (r = 0.50, p = 0.12). At T12 this relationship between MDA and cotinine was still present in the reducers (r = 0.70, p < 0.05), while the scatter of points in quitters was completely dispersed (r = (0.09). These results show that smoking cessation but not smoking reduction is associated with decreased markers of oxidative stress in the plasma of active cigarette smokers. PMID- 11197315 TI - Effect of cigarette smoking on coumarin metabolism in humans. AB - Extant data, mostly from studies in vitro, suggest that coumarin and nicotine are both metabolized by CYP2A6, a cytochrome P450 isozyme. In order to investigate this issue further, the activity of this enzyme in vivo was measured in 37 non smokers and 37 smokers using coumarin (2.0 mg, PO) as the metabolic probe. The percentage of coumarin metabolized to 7-hydroxycoumarin in 8 h was measured in urine by high-pressure liquid chromatography. There was more than 10-fold variability in coumarin metabolism in both groups. Coumarin metabolism was significantly reduced in smokers (46.6 +/- 4.4%) as compared to non-smokers (66.4 +/- 3.5%; p < or = .001). The results support previous in vitro findings that both coumarin and nicotine are metabolized, at least in part, by a common pathway, which most likely is CYP2A6. PMID- 11197316 TI - Socioeconomic status, ethnicity, and environmental tobacco exposure among non smoking females. AB - This study examined the relationship between socioeconomic status (SES) and environmental tobacco smoke (ETS) exposure among non-smoking females, determined which SES variable(s) were most strongly associated with ETS exposure, and examined whether the relationship between SES and ETS exposure was the same for Blacks and Whites. Participants were 404 never-smoker females recruited in the community. Independent variables included income, education, occupation, median income within zip code of participants' residence, and ethnicity. Number of days per week exposed to ETS in the past year was the dependent variable. There was a significant correlation between CO levels (parts per million, ppm) and self reported ETS exposure (r = 0.22, p < 0.001). The mean CO level exposure was 1.81 +/- 1.19 ppm, and the mean number of days per week of ETS exposure was 4.72 +/- 4.71. The most frequent source of ETS exposure was at public places (64.4%). Although Blacks tended to report higher ETS exposure than Whites (p = 0.08), this tendency disappeared when SES indicators were entered in the model. Correlations among SES indicators were either non-significant or very modest suggesting that different SES indicators may not measure the same construct. Education was the only SES variable that was significantly associated with ETS exposure in this population. The relationship between SES and ETS exposure was similar for both Blacks and Whites. These findings suggest that education may be the most important factor to be considered when designing interventions to decrease ETS exposure among young non-smoking females (e.g., public education of the hazards of ETS exposure and awareness of existing tobacco-control laws and regulations). PMID- 11197317 TI - A self-help cessation program for smokeless tobacco users: comparison of two interventions. AB - While the use of smokeless tobacco products has increased, there has been a paucity of research evaluating interventions to help users quit. This study is the first large-scale randomized trial evaluating two levels of self-help cessation intervention with adult smokeless tobacco (SLT) users. Smokeless users in five Northwest states were recruited to call a toll-free number and 1069 users were randomized to receive one of two interventions, Manual Only (MAN) or Assisted Self-Help (ASH), who received a video and two support phone calls in addition to the manual. The study demonstrated that low-cost minimal interventions done by mail and phone can help a sizable proportion of SLT users quit both SLT and all tobacco use. Follow-up data at 6 months showed that subjects in the ASH condition had a significantly higher quit rate for both smokeless (23.4% vs. 18.4%, p < 0.05) and all tobacco use (21.1% vs. 16.5%, p < 0.05), using an intent-to-treat model. Further analysis revealed that use of the recommended cessation procedures mediated the effect of intervention condition on outcomes. This may be the result of phone counselors getting subjects to carry out behavioral cessation procedures. Public health implications for this intervention are discussed. PMID- 11197318 TI - Efficacy of the nicotine patch for relief of craving and withdrawal 7-10 weeks after cessation. AB - The objective of this study was to test the efficacy of the nicotine patch for relief of craving and withdrawal beyond 6 weeks (during weeks 7-10), among heavy, dependent smokers, using a multicenter, randomized, double-blind, placebo controlled trial. The subjects were 421 nicotine-dependent smokers who had quit smoking with the NicoDerm CQ nicotine patch, recruited from among enrollees in the NicoDerm CQ Committed Quitters behavioral program. Following 6 weeks of 21-mg active patch use, participants who had not relapsed were randomized to receive either active or placebo patches for an additional 4 weeks with tapering (14-mg patch in weeks 7-8 and 7-mg patch in weeks 9-10). Craving and withdrawal symptoms were assessed daily by phone interview during weeks 7-10 following cessation. The active patch group reported significantly lower craving and withdrawal, and higher positive mood scores in weeks 7-8 (p < 0.001, 0.001, and 0.03, respectively) and weeks 9-10 (p < 0.02, 0.01, and 0.02, respectively) compared to the placebo group. It was concluded that some smokers may be best served by 10 weeks of patch treatment. This study demonstrated the utility of continuing patch treatment for symptom relief in weeks 7-10 of abstinence. Future research should examine the optimal duration of treatment, which may vary across different classes of smokers. PMID- 11197319 TI - Reducing tobacco use: a report of the Surgeon General--executive summary. PMID- 11197320 TI - Phylogenetic origin of a secondary pathway: the case of pyrrolizidine alkaloids. AB - Recent studies have revealed high sequence similarity between homospermidine synthase (HSS), the first pathway-specific enzyme in the biosynthesis of pyrrolizidine alkaloids, a class of sporadically occurring plant defence compounds, and deoxyhypusine synthase (DHS), a ubiquitous enzyme involved in the post-translational activation of the eukaryotic initiation factor 5A (eIF5A). The recruitment of DHS during the evolution of the alkaloid pathway is discussed and interpreted as evolution by change of function. PMID- 11197321 TI - The role of hexokinase in plant sugar signal transduction and growth and development. AB - Previous studies have revealed a central role of Arabidopsis thaliana hexokinases (AtHXK1 and AtHXK2) in the glucose repression of photosynthetic genes and early seedling development. However, it remains unclear whether HXK can modulate the expression of diverse sugar-regulated genes. On the basis of the results of analyses of gene expression in HXK transgenic plants, we suggest that three distinct glucose signal transduction pathways exist in plants. The first is an AtHXK1-dependent pathway in which gene expression is correlated with the AtHXK1 mediated signaling function. The second is a glycolysis-dependent pathway that is influenced by the catalytic activity of both AtHXK1 and the heterologous yeast Hxk2. The last is an AtHXK1-independent pathway in which gene expression is independent of AtHXK1. Further investigation of HXK transgenic Arabidopsis discloses a role of HXK in glucose-dependent growth and senescence. In the absence of exogenous glucose, plant growth is limited to the seedling stage with restricted true leaf development even after a 3-week culture on MS medium. In the presence of glucose, however, over-expressing Arabidopsis or yeast HXK in plants results in the repression of growth and true leaf development, and early senescence, while under-expressing AtHXK1 delays the senescence process. These studies reveal multiple glucose signal transduction pathways that control diverse genes and processes that are intimately linked to developmental stages and environmental conditions. PMID- 11197322 TI - Caleosins: Ca2+-binding proteins associated with lipid bodies. AB - We have previously identified a rice gene encoding a 27 kDa protein with a single Ca2+-binding EF-hand and a putative membrane anchor. We report here similar genes termed caleosins, CLO, in other plants and fungi; they comprise a multigene family of at least five members in Arabidopsis (AtClo1-5). Northern hybridization demonstrated that AtClo2-4 mRNAs levels were low in various tissues, while AtClo1 mRNA levels were high in developing embryos and mature seeds. Analysis of transgenic Arabidopsis plants expressing the GUS reporter under control of the AtClo1 promoter showed strong levels of expression in developing embryos and also in root tip cells. Antibodies raised against AtCLO1 were used to detect caleosin in cellular fractions of Arabidopsis and rapeseed. This indicated that caleosins are a novel class of lipid body proteins, which may also be associated with an ER subdomain. PMID- 11197323 TI - Increased abundance of MTD1 and MTD2 mRNAs in nodules of decapitated Medicago truncatula. AB - To gain insight into the molecular processes occurring in root nodule metabolism after stress, we used a mRNA differential display (DDRT-PCR) approach to identify cDNAs corresponding to genes whose expression is enhanced in nodules of decapitated Medicago truncatula plants. Two full-length cDNAs of plant origin were isolated (MTD1 and MTD2). Sequence analysis revealed that MTD1 is identical to an EST clone (accession number AW559774) expressed in roots of M. truncatula upon infection with Phytophthora medicaginis, while MTD2 is highly homologous to an Arabidopsis thaliana gene (accession number AL133292) coding for a RNA binding like protein. The two mRNAs started to accumulate in root nodules at 4 h after plant decapitation and reached even higher transcript levels at 24 h from the imposition of the treatment. MTD1 and MTD2 mRNAs were mainly induced in nodules, with very little induction in roots. The abundance of the two transcripts did not change in response to other perturbations known to decrease nitrogenase activity, such as nitrate and Ar/O2 treatments. Our results suggest that MTD1 and MTD2 represent transcripts that accumulate locally in nodules and may be involved in changes in nodule metabolism in response to decapitation. PMID- 11197324 TI - Identification and characterization of a heat-induced isoform of aldolase in oat chloroplast. AB - An analysis of protein synthesis at elevated temperatures in oat (Avena sativa) leaves revealed a heat-induced 44 kDa polypeptide. A cDNA library of heat-treated leaves was constructed and screened with specific antibodies raised against this 44 kDa polypeptide. A clone encoding the 44 kDa protein was identified as a form of the chloroplast-localized fructose-bisphosphate aldolase (EC 4.1.2.13). Northern and western blot analyses indicated heat-induced accumulation of the chloroplast aldolase isoform at both the RNA and protein level. Heat inducibility was restricted to the chloroplastic form of the enzyme, and was not observed for the cytoplasmic aldolase. The heat-induced isoform co-purified with thykaloid fractions, as confirmed by immunoassay and activity analyses. However, when thylakoid membranes were treated with proteinase K, the aldolase isoform completely disappeared, suggesting that this enzyme is not embedded but rather tends to adhere to the chloroplast membranes. Immunoblot analysis of other plant species revealed similar heat induction of thykaloid-associated aldolase homologues, suggesting the possible existence of a universal control mechanism for this enzyme's heat tolerance PMID- 11197325 TI - The Arabidopsis thaliana PPX/PP4 phosphatases: molecular cloning and structural organization of the genes and immunolocalization of the proteins to plastids. AB - The PPX/PP4 Ser/Thr protein phosphatases belong to the type 2A phosphatase subfamily and are present in most eukaryotic organisms. We have previously isolated two closely related DNAs encoding PPX isoforms (PPX-1 and PPX-2) of Arabidopsis thaliana. Here we report the molecular cloning of the genes encoding these proteins. The genes PPX-1 and PPX-2 are composed of eight exons and seven introns located at equivalent positions related to the coding sequences. Whereas the intron-exon organization of the PPX genes is completely different from that of the PP2A-3/PP2A-4 A. thaliana family, specific intron-exon boundaries are conserved among PPX genes from distantly related organisms. Based on GUS expression, both PPX genes show the same spatial and temporal pattern of expression: they are expressed in all the organs and tissues analyzed, and from the earliest stage of development. When PPX proteins were localized to the root in semi-thin methacrylate sections by immunofluorescence, staining was predominantly confined to small organelles, shown to be plastids by co localization of PPX and ferredoxin. Interestingly, only some ferredoxin-positive plastids were also PPX-positive, and PPX staining was consistently brighter in the epidermis. The localization was confirmed with immunogold and electron microscopy. Our results suggest that, despite its strong sequence conservation, PPX in plants functions differently than in animals. PMID- 11197326 TI - Two rice MADS domain proteins interact with OsMADS1. AB - OsMADS1 is a MADS box gene controlling flower development in rice. In order to learn more about the function of OsMADS1, we searched for cellular proteins interacting with OsMADS1 employing the yeast two-hybrid system. Two novel proteins with MADS domains, which were named OsMADS14 and OsMADS15, were isolated from a rice cDNA library. OsMADS14 and -15 are highly homologous to the maize MADS box gene ZAP1 which is an orthologue of the floral homeotic gene APETALA1 (AP1). Interactions among the three MADS domain proteins were confirmed by in vitro experiments using GST-fused OsMADS1 expressed in Escherichia coli and in vitro translated proteins of OsMADS14 and -15. We determined which domains in OsMADS1, -14, and -15 were required for protein-protein interaction employing the two-hybrid system and pull-down experiments. While the K domain was essential for protein-protein interaction, a region preceded by the K domain augmented this interaction. Interestingly, the C-terminal region of OsMADS1 functioned as a transcriptional activation domain in yeast and mammalian cells, while, on the other hand, the C domains of OsMADS14 and -15 exhibited only very weak transcriptional activator functionality, if any at all. PMID- 11197327 TI - The sequence and secondary structure of the 3'-UTR affect 3'-end maturation, RNA accumulation, and translation in tobacco chloroplasts. AB - RNA maturation and modulation of RNA stability play important roles in chloroplast gene expression. In vitro and in vivo studies have shown that both the 5'- and 3'-untranslated regions (UTRs) contain sequence and structural elements that guide these processes, and interact with specific proteins. We have previously characterized the spinach chloroplast petD 3'-UTR in detail by in vitro approaches. This stem-loop forming sequence is a weak terminator but is required for RNA maturation and also exhibits sequence-specific protein binding. To test petD 3'-UTR function in vivo, tobacco chloroplast transformants were generated containing uidA reporter genes flanked by variants of the petD 3'-UTR, including one which does not form an RNA-protein complex in vitro, and one which lacks a stem-loop structure. Analysis of uidA mRNA indicated that a stable secondary structure is required to accumulate a discrete mRNA, and that changes in the 3'-UTR sequence which affect protein binding in vitro can also affect RNA metabolism in vivo. The 3'-UTR also influenced beta-glucuronidase protein accumulation, but not in proportion to RNA levels. These results raise the possibility that in tobacco chloroplasts, the 3'-UTR may influence translational yield. PMID- 11197328 TI - Binding of cell type-specific nuclear proteins to the 5'-flanking region of maize C4 phosphoenolpyruvate carboxylase gene confers its differential transcription in mesophyll cells. AB - C4-type phosphenolpyruvate carboxylase (C4PEPC) acts as a primary carbon assimilatory enzyme in the C4 photosynthetic pathway. The maize C4PEPC gene (C4Ppc1) is specifically expressed in mesophyll cells (MC) of light-grown leaves, but the molecular mechanism responsible for its cell type-specific expression has not been characterized. In this study, we introduced a chimeric maize C4Ppc1 5' flanking region/beta-glucuronidase (GUS) gene into maize plants by Agrobacterium mediated transformation. Activity assay and histochemical staining showed that GUS is almost exclusively localized in leaf MC of transgenic maize plants. This observation suggests that the introduced 5' region of maize C4Ppc1 contains the necessary cis element(s) for its specific expression in MC. Next, we investigated whether the 5' region of the maize gene interacts with nuclear proteins in a cell type-specific manner. By gel shift assays with nuclear extracts prepared from MC or bundle sheath cells (BSC), cell type-specific DNA-protein interactions were detected: nuclear factors PEP(Ib) and PEP(Ic) are specific to MC whereas PEP(Ia) and PEP(IIa) are specific to BSC. Light alters the binding activity of these factors. These interactions were not detected in the assay with nuclear extract prepared from root, or competed out by oligonucleotides corresponding to the binding sites for the maize nuclear protein, PEP-I, which is known to bind specifically to the promoter region of C4Ppc1. The results suggest that novel cell type-specific positive and negative nuclear factors bind to the maize C4Ppc1 5'-flanking region and regulate its differential transcription in MC in a light dependent manner. PMID- 11197329 TI - Genes normally expressed in the endosperm are expressed at early stages of microspore embryogenesis in maize. AB - Reproduction in flowering plants is characterized by double fertilization and the resulting formation of both the zygotic embryo and the associated endosperm. In many species it is possible to experimentally deviate pollen development towards an embryogenic pathway. This developmental switch, referred to as microspore embryogenesis or androgenesis, leads to the formation of embryos similar to zygotic embryos. In a screen for genes specifically expressed during early androgenesis, two maize genes were isolated by mRNA differential display. Both genes represent new molecular markers expressed at a very young stage of androgenic embryogenesis. When their expression pattern was studied during normal reproductive development, both showed early endosperm-specific expression. Investigation of the cytological features of young androgenic embryos revealed that they present a partially coenocytic organization similar to that of early endosperm. These findings suggest that maize androgenesis may possibly involve both embryogenesis and the establishment of endosperm-like components. PMID- 11197330 TI - 2,4-Disubstituted oxazoles and thiazoles as latent pharmacophores for diacylhydrazine of SC-51089, a potent PGE2 antagonist. AB - 8-Chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[1-oxo-3-(4 pyridinyl)propyl]hydrazide, monohydrochloride (1, SC-51089) is a functional PGE2 antagonist selective for the EP1 receptor subtype with antinociceptive activity. Analogues of SC-51089, in which the diacylhydrazine moiety has been replaced with 2,4-disubstituted-oxazoles and-thiazoles, are described. PMID- 11197331 TI - Synthesis and characterization of a tetranucleotide analogue containing alternating phosphonate-amide backbone linkages. AB - Described herein is the synthesis and characterization of a tetranucleotide, 5' dC-phosphonate-T-amide-T-ophosphonate-dC (III), in which the C-T and T-C steps contain a phosphonate backbone bond and T-T is a peptide nucleic acid dimer unit (neutral backbone). The 5'- and 3'-OH groups of the tetramer can be further derivatized and, thus, the compound is a potential building block for longer oligonucleotides which will contain alternating backbone modifications at designated positions. The synthesis involved first the preparation of two hybrid peptide-deoxyribose dinucleotides, CT-CO (I) and N-CT (II) (C and T are nucleobases; CO and N are carboxylic and amino terminal, respectively); each is linked through a phosphonate linkage. A condensation reaction between the two dimers, followed by deprotection, resulted in the formation of a peptide linkage to give the desired tetramer III. The reaction conditions used are mild to afford products in moderate to excellent yields. The DNA-PNA-DNA tetramer, d(CTTC), is a substrate for T4 kinase but fails to give a ligation product, even though NMR shows weak interactions between the tetramer III with its complementary sequence, d(GAAG). PMID- 11197332 TI - Specific inhibitor of puromycin-sensitive aminopeptidase with a homophthalimide skeleton: identification of the target molecule and a structure-activity relationship study. AB - 2-(2,6-Diethylphenyl)-1,2,3,4-tetrahydroisoquinoline-1,3-dione (2: PIQ-22) was found to be a potent and specific inhibitor of puromycin-sensitive aminopeptidase (PSA). Lineweaver-Burk plot analysis showed that PSA is inhibited by PIQ-22 in a non-competitive manner. Structure -activity relationship studies indicated that tautomerism of the imidobenzoylketone group in the cyclic imide moiety of the PIQ 22 skeleton is important for the inhibitory activity. PMID- 11197333 TI - A phosphatidylinositol 3,4,5-trisphosphate analogue with low serum protein binding affinity. AB - Phosphatidylinositol 3,4,5-trisphosphate (PIP3) plays an important role in the regulation of diverse physiological functions. Recent evidence indicates that PIP3 is cell permeant, and can be added exogenously to modulate cellular responses. However, like many other phospholipids, PIP3 binds serum proteins with high affinity, resulting in rapid deactivation of this lipid second messenger. Our study indicates that bovine serum albumin (BSA) at concentrations as low as 10 microg/mL abrogated the biological activity of dipalmitoyl-PIP3. This nonspecific interaction with serum proteins hampers the use of PIP3 in biological studies where serum is needed. We report here an ether-linked PIP3 analogue, 1-O (1-O-hexadecyl-2-O-methyl-sn-glycero-3-phosphoryl)-myo-inositol 3,4,5 trisphosphate (C16Me-PIP3). which displays low serum protein-binding affinity while retaining the biological function of PIP3. The affinity of C16Me-PIP3 with BSA was two orders of magnitude lower than that of its dipalmitoyl-counterpart. Biochemical data indicate that C16Me-PIP3 was able to stimulate Ca2+ influx in T cells in the presence of moderate levels (up to 1 mg/mL) of BSA. Thus. C16Me-PIP3 may provide a useful tool to study the physiological function of phosphoinositide (PI) 3-kinase in vivo. PMID- 11197334 TI - Estrogen pyrazoles: defining the pyrazole core structure and the orientation of substituents in the ligand binding pocket of the estrogen receptor. AB - Previously, we reported that certain tetrasubstituted 1,3,5-triaryl-4-alkyl pyrazoles bind to the estrogen receptor (ER) with high affinity (Fink, B. E.; Mortenson, D. S.; Stauffer, S. R.; Aron, Z. D.; Katzenellenbogen, J. A. Chem. Biol. 1999, 6, 205-219; Stauffer, S. R.; Katzenellenbogen, J. A. J. Comb/. Chem. 2000, 2. 318 329; Stauffer, S. R.: Coletta, C. J.: Sun, J.; Tedesco, R., Katzenellenbogen, B. S.; Katzenellenbogen, J. A. J. Med. Chem. 2000, submitted). To investigate how cyclic permutation of the two nitrogen atoms of a pyrazole might affect ER binding affinity, we prepared a new pyrazole core isomer, namely a 1,3,4-triaryl-5-alkyl-pyrazole (2), to compare it with our original pyrazole (1). We also prepared several peripherally matched core pyrazole isomer sets to investigate whether the two pyrazole series share a common binding orientation. Our efficient, regioselective synthetic route to these pyrazoles relies on the acylation of a hydrazone anion, followed by cyclization, halogenation, and Suzuki coupling. We found that the ER accommodates 1,3,4-triaryl-pyrazoles of the isomeric series only somewhat less well than the original 1,3,5-triaryl series, and it appears that both series share a common binding mode. This preferred orientation for the 1,3,5-triaryl-4-alkyl-pyrazoles is supported by binding affinity measurements of analogues in which the phenolic hydroxyl groups were systematically removed from each of the three aryl groups, and the orientation is consistent, as well, with molecular modeling studies. These studies provide additional insight into the design of heterocyclic core structures for the development of high affinity ER ligands by combinatorial methods. PMID- 11197335 TI - Triarylpyrazoles with basic side chains: development of pyrazole-based estrogen receptor antagonists. AB - Recently, we developed a novel triaryl-substituted pyrazole ligand system that has high affinity for the estrogen receptor (ER) (Fink, B. E.: Mortenson, D. S.: Stauffer, S. R.; Aron, Z. D.: Katzenellenbogen, J. A. Chem. Biol. 1999, 6, 205). Subsequent work has shown that some analogues in this series are very selective for the ERalpha subtype in terms of binding affinity and agonist potency (Stauffer, S. R.: Coletta, C. J.: Tedesco. R.: Sun, J.: Katzenellenbogen, J. A. J. Med. Chem. 2000, submitted). We now investigate how this pyrazole ER agonist system might be converted into an antagonist or a selective estrogen receptor modifier (SERM) by incorporating a basic or polar side chain like those typically found in antiestrogens and known to be essential determinants of their mixed agonist/antagonist character. We selected an N-piperidinyl-ethyl chain as a first attempt, and introduced it at the four possible sites of substitution on the pyrazole core structure to determine the orientation that the pyrazole might adopt in the ER ligand binding pocket. Of these four, the C(5) piperidinyl-ethoxy substituted pyrazole 5 had by far the highest affinity. Also, it bound to the ER subtype alpha (ERalpha) with 20-fold higher affinity than to ERbeta. In cell based transcription assays, pyrazole 5 was an antagonist on both ERalpha and ERbeta, and it was also more potent on ERalpha. Based on structure-binding affinity relationships and on molecular modeling studies of these pyrazoles in a crystal structure of the ERalpha-raloxifene complex, we propose that pyrazoles having a basic substituent on the C(5) phenyl group adopt a binding mode that is different from that of the pyrazole agonists that lack this group. The most favorable orientation appears to be one which places the N(1) phenol in the A ring binding pocket so that the basic side chain can adopt an orientation similar to that of the basic side chain of raloxifene. PMID- 11197336 TI - Synthesis and cytotoxicity of 4'-C- and 5'-C-substituted toyocamycins. AB - Toyocamycin and some analogues have shown potent antitumor activities; however, none of them could be used clinically primarily owing to their cytotoxicity to normal human cells. In order to overcome the weakness of these nucleoside analogues, substitution of a variety of modified sugars for the ribofuranose was explored in our laboratories with expectation that certain sugar-modified toyocamycin analogues may be selectively cytotoxic to cancer cells. In this article, we report synthesis and cytotoxicity of 4'-C- and 5'-C-substituted toyocamycins, which were prepared via the condensations of 4-C- and 5-C substituted ribofuranose derivatives 11, 12, 13, 20, 21, and 26 with the silylated form of 4-amino-6-bromo-5-cyanopyrrolo[2,3-]pyrimidine (27) and subsequent debromination and debenzoylation. When compared to the parent toyocamycin, all these analogues showed much lower cytotoxicity to human prostate cancer cells (HTB-81), mouse melanoma cancer cells (B16) as well as normal human fibroblasts. Compound 1e showed a significant cytotoxicity to the prostate cancer cells and a moderate selectivity. The results suggested that sugar modifications, especially those that may affect phosphorylation of nucleosides, could alter cytotoxicity profile significantly. PMID- 11197337 TI - Synthesis and bioactivity of 2,4-diacyl analogues of paclitaxel. AB - The 2,4-diacyl paclitaxel analogues 8a-8r were prepared from paclitaxel by acylation of 4-deacetyl-2-debenzoylpaclitaxel 1,2-carbonate (3) followed either by hydrolysis of the carbonate and acylation or by direct treatment of the carbonate with an aryllithium. Some of the resulting derivatives showed significantly improved tubulin assembly activity and cytotoxicity as compared with paclitaxel; in some cases this improvement was especially significant for paclitaxel-resistant cell lines. PMID- 11197338 TI - Iantherans A and B, unique dimeric polybrominated benzofurans as Na,K-ATPase inhibitors from a marine sponge, Ianthella sp. AB - Two novel tetrabrominated benzofuran derivatives, named iantherans A and B, were isolated from an Australian marine sponge of the genus lanthella. The unique structures comprised of 2,3-bis(sulfooxy)-1,3-butadiene and two brominated benzofuran moieties were determined by spectroscopic and chemical methods. Iantheran A has a (Z,Z)-1,3-butadiene moiety, whereas iantheran B is the geometric isomer possessing a (Z,E)-1,3-butadiene moiety. The inhibitory activities of the iantherans and their derivatives against Na,K-ATPase as well as the efficacy of iantheran A against other several enzymes were evaluated. PMID- 11197339 TI - N-(Hydroxyaminocarbonyl)phenylalanine: a novel class of inhibitor for carboxypeptidase A. AB - N-(Hydroxyaminocarbonyl)phenylalanine (1) was designed rationally as a new type of inhibitor for carboxypeptidase A (CPA). The designed inhibitor was readily prepared from phenylalnine benzyl ester in two steps and evaluated to find that rac-1 inhibits CPA in a competitive fashion with the Ki value of 2.09 microM. Surprisingly, inhibitor 1 having the D-configuration is more potent (Ki = 1.54 microM) than its antipode by about 3-fold. A possible explanation for the stereochemistry observed in the inhibition of CPA with 1 is presented. PMID- 11197341 TI - Enzyme-catalyzed prodrug approaches for the histamine H3-receptor agonist (R) alpha-methylhistamine. AB - Five novel prodrug types of the potent and selective histamine H3-receptor agonist (R)-alpha-methylhistamine (1) were prepared and pharmacologically tested in vitro as well as in vivo. In particular, an amide of fatty acid, mono- and dicarbamates, an (acyloxy)alkylcarbamate, and a diphthalidyl derivative were synthesized, all of which require initial prodrug activation through an enzyme catalyzed reaction in contrast to formerly developed azomethine prodrugs which are cleaved by chemical hydrolysis only. Further drug liberation may ensue spontaneously in a cascade to give 1. Since they have diverse stabilities the prodrugs were investigated for drug liberation in vitro under neutral, acidic, and basic conditions at different temperatures as well as with liver homogenates. In vivo investigation of prodrugs after oral administration to mice proved that the fatty amide 2, the Nalpha-methylcarbamate 4a, and the Nalpha-(1 (acetyloxy)ethylcarbamate) 5 showed moderate to high plasma levels of 1. Compound 5 displayed even more than 2.5 times the AUC for 1 than that of the reference azomethine prodrug BP2.94 in the periphery and also displayed a detectable drug level in the central nervous system. It was shown that prodrug approaches based on an initial enzyme-catalyzed liberation step are successfully applicable to different pro-moieties for improved bioavailability and prolonged half-live. These approaches may also be used for other aminergic compounds of this class to optimize pharmacokinetic behavior. PMID- 11197340 TI - N-(3-Acyloxy-2-benzylpropyl)-N'-(4-hydroxy-3-methoxybenzyl) thiourea derivatives as potent vanilloid receptor agonists and analgesics. AB - A series of N-(3-acyloxy-2-benzylpropyl)-N'-(4-hydroxy-3-methoxybenzyl) thiourea derivatives were investigated as vanilloid receptor ligands in an effort to discover a novel class of analgesics. The proposed pharmacophore model of resiniferatoxin. which includes the C20 homovanillic moiety, the C3-carbonyl and the orthoester phenyl ring as key pharmacophoric groups, was utilized as a guide for drug design. The compounds were synthesized after several steps from diethylmalonate and evaluated in vitro in a receptor binding assay and in a capsaicin-activated channel assay. Additional evaluation of analgesic activity, anti-inflammatory activity and pungency was conducted in animal models by the writhing test, the ear edema assay, and the eye-wiping test, respectively. Among the new compounds, 23 and 28 were found to be the most potent receptor agonists of the series with Ki values of 19 nM and 11 nM, respectively. Their strong in vitro potencies were also reflected by an excellent analgesic profile in animal tests with ED50 values of 0.5 microg kg for 23 and 1.0 microg/kg for 28. Relative to capsaicin these compounds appear to be ca. 600 and 300 times more potent. Both 23 and 28 were found to be less pungent than capsaicin based on the eye-wiping test. However, the compounds did not show significant anti-inflammatory activity. A molecular modeling study comparing the energy-minimized structures of resiniferatoxin and 35 demonstrated a good correlation in the spatial disposition of the corresponding key pharmacophores. The thioureas described in this investigation, which were designed as simplified resiniferatoxin surrogates, represent a novel class of potent vanilloid receptor agonists endowed with potent analgesic activity and reduced pungency. PMID- 11197342 TI - Mechanism of toxicity of esters of caffeic and dihydrocaffeic acids. AB - Ten esters each of caffeic acid and dihydrocaffeic acid have recently been synthesized. Cytotoxicity evaluations of these esters versus L1210 leukemia and MCF-7 breast cancer cells in culture have led to the delineation of substantially different QSAR for each series. The L1210 QSAR for dihydrocaffeic acid esters resembles the QSAR obtained for simple phenols and estrogenic phenols. However, the QSAR pertaining to the caffeic acid esters differs considerably from its sister QSAR. This difference may be attributed to the presence of the olefinic linkage in the side chain. The octyl ester of caffeic acid is nearly ten times as toxic to the leukemia cells than the widely studied phenethyl ester, CAPE. PMID- 11197343 TI - Synthesis and stereostructure-activity relationship of three asymmetric center pyrethroids: 2-methyl-3-phenylcyclopropylmethyl 3-phenoxybenzyl ether and cyanohydrin ester. AB - 2-Methyl-3-phenylcyclopropylmethyl 3-phenoxybenzyl ether 2 and cyanohydrin ester 3, a couple of pyrethroids with three asymmetric centers, were synthesized. Of each of the four diastereomers of 2 and 3, only the (1R*,2R*,3R*)-2a and 3a showed significant insecticidal activities. Dual sets of enantiomers [(1R,2R,3R) (-)-2a and (1S,2S,3S)-(+)-2a] and [(1R,2R,3R)-(-)-3a and (1S,2S,3S)-(+)-3a] were synthesized through the asymmetric cyclopropanation using the Aratani catalyst. Significant separations of insecticidal activities were observed between both the enantiomers against the tobacco cutworm (Spodoptera litura) and the common mosquito (Culex pipiens pallens); (1S,2S,3S)-(+)-2a and (+)-3a showed higher activities than their antipodes (1R,2R,3R)(-)-2a and (-)-3a. This result is the second example of such synthetic pyrethroids with three asymmetric centers. PMID- 11197344 TI - Antioxidant constituents from rhubarb: structural requirements of stilbenes for the activity and structures of two new anthraquinone glucosides. AB - The methanolic extracts from five kinds of rhubarb were found to show scavenging activity for DPPH radical and .O2-. Two new anthraquinone glucosides were isolated from the rhizome of Rheum undulatum L. together with two anthraquinone glucosides, a naphthalene glucoside, and 10 stilbenes. In the screening test for radical scavenging activity of rhubarb constituents, stilbenes and a naphthalene glucoside showed activity, but anthraquinones and sennosides did not. In addition, most stilbenes inhibited lipid peroxidation of erythrocyte membrane by tert-butyl hydroperoxide. Detailed examination of the scavenging effect on various related compounds suggested the following structural requirements; 1) phenolic hydroxyl groups are essential to show the activity; 2) galloyl moiety enhances the activity; 3) glucoside moiety reduces the activity; 4) dihydrostilbene derivatives maintain the scavenging activity for the DPPH radical, but they show weak activity for .O2-. In addition, several stilbenes with both the 3-hydroxyl and 4'-methoxyl groups inhibited xanthine oxidase. PMID- 11197345 TI - Chemical synthesis and biological investigation of a 77-mer oligoribonucleotide with a sequence corresponding to E. coli tRNA(Asp). AB - A 77-mer RNA with the sequence of Eschlerichia coli tRNA(Asp) has been chemically synthesised using standard automated phosphoramidite chemistry with the coupling reagent 4,5-dicyanoimidazole (DCI). The synthesis was carried out on a 1000 A CPG column and. after deprotection and gel purification, a yield of about 7 mmol with a purity of > 95% was reproducibly obtained. By comparing automated synthesis of the 77-mer RNA using 1H-tetrazole and DCI as activator, DCI is advantageous in producing longer RNAs. However, for shorter RNAs ( <40 mer) no difference could be observed. In addition to the all-ribo tRNA(Asp) carrying the wild-type sequence, two variants were synthesised, one with a single C to G48 mutation and the second with a 2'-deoxy modification at C48. The three tRNAs were tested for their aminoacylation efficiency and high affinity binding to E. coli RNase P RNA. The results demonstrate that chemically synthesised 77-mer oligoribonucleotides can be successfully used for structure function studies. PMID- 11197346 TI - Participation of the beta-hydroxyketone part for potent cytotoxicity of callystatin A, a spongean polyketide. AB - The participation of the beta-hydroxyketone part of callystatin A in the potent cytotoxicity was analyzed through the analogue-syntheses and the assessment of their biological potencies. The ketonic carbonyl, the 19-hydroxyl, and the three asymmetric methyl groups located in the beta-hydroxyketone part of callystatin A were revealed to contribute to the cytotoxic potency, respectively. Moreover, the alpha,beta-unsaturated delta-lactone portion was shown to serve as a conclusive functional group for the cytotoxic activity. PMID- 11197347 TI - Molecular determinants of non-specific recognition of delta, mu, and kappa opioid receptors. AB - Identification of the molecular determinants of recognition common to all three opioid receptors embedded in a single three-dimensional (3D) non-specific recognition pharmacophore has been carried out. The working hypothesis that underlies the computational study reported here is that ligands that bind with significant affinity to all three cloned opioid receptors, delta, mu, and kappa, but with different combinations of activation and inhibition properties at these receptors, could be promising behaviorally selective analgesics with diminished side effects. The study presented here represents the first step towards the rational design of such therapeutic agents. The common 3D pharmacophore developed for recognition of delta, mu, and kappa opioid receptors was based on the receptor affinities determined for 23 different opioid ligands that display no specificity for any of the receptor subtypes. The pharmacophore centers identified are a protonated amine, two hydrophobic groups, and the centroid of an aromatic group in a geometric arrangement common to all 23, non-specific, opioid ligands studied. Using this three-dimensional pharmacophore as a query for searching 3D structural databases, novel compounds potentially involved in non specific recognition of delta, mu, and kappa opioid receptors were retrieved. These compounds can be valuable candidates for novel behaviorally selective analgesics with diminished or no side effects, and thus with potential therapeutic usefulness. PMID- 11197348 TI - Alternative heterocycles for DNA recognition: an N-methylpyrazole/N-methylpyrrole pair specifies for A.T/T.A base pairs. AB - Side-by-side pairs of three five-membered rings, N-methylpyrrole (Py), N methylimidazole (Im), and N-methylhydroxy-pyrrole (Hp), have been demonstrated to distinguish each of the four Watson Crick base pairs in the minor groove of DNA. However, not all DNA sequences targeted by these pairing rules achieve affinities and specificities comparable to DNA binding proteins. We have initiated a search for new heterocycles which can expand the sequence repetoire currently available. Two heterocyclic aromatic amino acids. N-methylpyrazole (Pz) and 4-methylthiazole (Th), were incorporated into a single position of an eight-ring polyamide of sequence ImImXPy-gamma-lmPyPyPy-beta-Dp to examine the modulation of affinity and specificity for DNA binding by a Pz/Py pair and or a Th/Py pair. The X/Py pairings Pz/Py and Th/Py were evaluated by quantitative DNase I footprint titrations on a DNA fragment with the four sites 5'-TGGNCA-3' (N=T, A, G, C). The Pz/Py pair binds T.A and A.T with similar affinity to a Py/Py pair but with improved specificity. disfavoring both G.C and C.G by about 100-fold. The Th/Py pair binds poorly to all four Watson Crick base pairs. These results demonstrate that in some instances new heterocyclic aromatic amino acid pairs can be incorporated into imidazole-pyrrole polyamides to mimic the DNA specificity of Py/Py pairs which may be relevant as biological criteria in animal studies become important. PMID- 11197349 TI - New constituents and antiplatelet aggregation and anti-HIV principles of Artemisia capillaris. AB - Five new constituents including a flavonoid, artemisidin A (1), and four coumarins, artemicapins A (2), B (3), C (4) and D (5), together with 70 known compounds (6-75), have been isolated and characterized from the aerial part of Artemisia capillaris. The structures of these compounds were determined from spectral analyses and/or chemical evidence. Among them, 15 compounds (3, 6, 10, 18. 30-32, 38-41, 44, 45, 51, and 55) showed antiplatelet aggregation activity and three compounds (10, 17, and 51) demonstrated significant activity against HIV replication in H9 lymphocytic cells. PMID- 11197350 TI - Design and synthesis of a multivalent homing device for targeting to murine CD22. AB - CD22 is a cell-surface glycoprotein uniquely located on mature B-cells and B-cell derived tumour cells. Current evidence suggests that binding of endogenous ligands to CD22 leads to modulation of B-cell activation by antigen. Incidentally, however, B-cell activation may derail. and lead to an undesired immune response, for example in cases of allergy, rheumatoid arthritis and Crohn's disease. In this situation, synthetic high-affinity ligands for CD22 may be of therapeutic value as inhibitors of B-cell activation. Recent studies have revealed that natural ligands for CD22 contain the trisaccharide NeuAc alpha-2,6 Lac as the basic binding motif. In addition, it has been demonstrated that binding to CD22 is strongly enhanced by multivalent presentation of the basic binding motif (cluster effect). In this paper. the stepwise development of a novel multivalent high-affinity ligand for CD22 is described. In the first stage, a series of monovalent NeuAc alpha-2,6-Glc(Y)X type binding motifs was prepared, and their affinity for murine CD22 was monitored, to obtain more insight into the effect of separate structure elements on ligand recognition. In the second stage, we prepared a trivalent cluster, based on the monovalent motif that displayed the highest affinity for CD22, NeuAc alpha-2,6-GlcNBzNO2OMe (7). This cluster, TRIS(NeuAc alpha-2,6-GlcNBzNO2)3 (52), displayed a more than 58-fold higher affinity for CD22 than the reference structure NeuAc alpha-2,6-LacOMe (10). To our knowledge, the cluster 52 is one of the most potent antagonists for CD22 yet synthesised. PMID- 11197351 TI - N-nitrosoanilines: a new class of caspase-3 inhibitors. AB - Caspases are a family of cysteine proteases activated during apoptosis. In cultured human endothelial cells, physiological levels of NO prevent apoptosis and interfere with the activation of the caspase cascade. Previous studies have demonstrated that NO inhibits the activity of caspase-3 by S-nitrosylation of the enzyme. In this study, the inhibitory effect of a new class of NO donors. N nitrosoaniline derivatives, were examined against caspase-3. Initially eight small molecule inhibitors bearing N-nitroso moieties were assayed. It was found that the presence of an electron-donating group on the phenyl ring led to better inhibitory potency, a trend consistent with the results from the previous papain studies. Based on the analysis of the enzyme and substrates' structures, two peptidyl N-nitrosoaniline inhibitors [Ac-DVAD-NNO (1) and Ac-DV-AMO (2)] were designed and synthesized. Both compounds exhibited enhanced inhibitory potency against caspase-3. PMID- 11197352 TI - Grants, not loans, for the developing world? PMID- 11197353 TI - Clinical picture: a newborn with gynaecomastia. PMID- 11197354 TI - Molecular quantification and mapping of lymph-node micrometastases in cervical cancer. AB - BACKGROUND: A proportion of patients with cancer and lymph nodes negative on histology will develop recurrence. Reverse-transcriptase PCR (RT-PCR) is a highly sensitive method for detection of lymph-node micrometastases, but accurate quantitative assessment has been difficult. METHODS: We studied primary tumours and 156 lymph nodes from 32 patients with cervical cancer (stage IA2, IB1, and IB2) and 32 lymph nodes from nine patients with benign disease. A fully quantitative, real-time RT-PCR assay was used to document absolute copy numbers of the epithelial marker cytokeratin 19. Primers and probe were designed not to amplify either of the two cytokeratin 19 pseudogenes. FINDINGS: All primary tumours and histologically involved lymph nodes (six) had more than 106 copies of cytokeratin 19 mRNA per microg total RNA. Expression of cytokeratin 19 (up to 1.1 x 10(5) copies per microg RNA) was detected in 66 (44%) of 150 histologically uninvolved lymph nodes, and in nodes from 16 of 32 patients with cervical cancer. 15 of these 16 patients with evidence of micrometastases had the highest cytokeratin 19 transcription level in a first lymph-node drainage station (three obturator, six internal, and six external iliac node). Transcription of cytokeratin 19 was found at a low level in just one of 32 lymph nodes obtained from nine patients with benign disease. Median copy number of cytokeratin 19 transcription was significantly higher (>10(3) copies) in association with adverse prognostic features. INTERPRETATION: The results suggest that about 50% of early-stage cervical cancers shed tumour cells to the pelvic lymph nodes. The amount of cytokeratin 19 expression was related to clinicopathological features. Further studies are required to document the clinical implications of molecular micrometastases. PMID- 11197355 TI - Is host endothelium a silver lining for allografts? PMID- 11197356 TI - Visualisation of presence, location, and transmural extent of healed Q-wave and non-Q-wave myocardial infarction. AB - BACKGROUND: A technical advance in contrast-enhanced magnetic resonance imaging (MRI) has significantly improved image quality. We investigated whether healed myocardial infarction can be visualised as hyperenhanced regions with this new technique, and whether assessment of the transmural extent of infarction yields new physiological data. METHODS: 82 MRI examinations were carried out in three groups: patients with healed myocardial infarction; patients with non-ischaemic cardiomyopathy; and healthy volunteers. Patients with healed myocardial infarction were prospectively enrolled after enyzmatically proven necrosis and imaged 3 months (SD 1) or 14 months (7) later. The MRI procedure used a segmented inversion-recovery gradient-echo sequence after gadolinium administration. Findings were compared with those of coronary angiography, electrocardiography, cine MRI, and creatine kinase measurements. FINDINGS: 29 (91%) of 32 patients with infarcts imaged at 3 months (13 non-Q-wave) and all of 19 imaged at 14 months (eight non-Q-wave) showed hyperenhancement. In patients in whom the infarct-related-artery was identified by angiography, 24 of 25 imaged at 3 months and all of 14 imaged at 14 months had hyperenhancement in the appropriate territory. None of the 20 patients with non-ischaemic cardiomyopathy or the 11 healthy volunteers showed hyperenhancement. Irrespective of the presence or absence of Q waves, the majority of patients with hyperenhancement had only non transmural involvement. Normal left-ventricular contraction was shown in seven patients examined at 3 months and three examined at 14 months, but in these cases hyperenhancement was limited to the subendocardium. INTERPRETATION: The presence, location, and transmural extent of healed Q-wave and non-Q-wave myocardial infarction can be accurately determined by contrast-enhanced MRI. PMID- 11197357 TI - Brand appearances in contemporary cinema films and contribution to global marketing of cigarettes. AB - BACKGROUND: The appearance of a cigarette brand in a cinema film gives the brand a certain distinction through its association with the characters and general tone of the film. Through the worldwide distribution of films, brands are promoted globally. We assessed the tobacco-brand appearances in a 10-year sample of contemporary films. METHODS: We viewed the contents of the top 25 US box office films for each year of release, from 1988 to 1997 (250 films in total). We compared the prevalence of brand appearances for films produced before a voluntary ban on paid product placement by the tobacco industry (1988-90) with films produced after the ban (1991-97). Tobacco-brand appearance was defined as the screen appearance of a brand name, logo, or identifiable trademark on products or product packaging, billboards, store-front advertising, or tobacco promotional items. We defined actor endorsement of a brand as the display of a brand while being handled or used by an actor. FINDINGS: More than 85% of the films contained tobacco use. Tobacco brands appeared in 70 (28%) films. Brand appearances were as common in films suitable for adolescent audiences as they were in films for adult audiences (32 vs 35%), and were also present in 20% of those rated for children. Prevalence of brand appearance did not change overall in relation to the ban. However, there was a striking increase in the type of brand appearance depicted, with actor endorsement increasing from 1% of films before the ban to 11% after. Four US cigarette brands accounted for 80% of brand appearances. Revenues outside the USA accounted for 49% of total revenues for these films, indicating a large international audience. INTERPRETATION: Tobacco brand appearances are common in films and are becoming increasingly endorsed by actors. The most highly advertised US cigarette brands account for most brand appearances, which suggests an advertising motive to this practice. PMID- 11197358 TI - Unexamined assumptions in explorations of upper limit for cases of variant Creutzfeldt-Jakob disease. PMID- 11197360 TI - Septicaemia in a pig-farm worker. PMID- 11197359 TI - Endothelial cell chimerism after renal transplantation and vascular rejection. AB - BACKGROUND: The blood vessels of a transplanted organ are the interface between donor and recipient. The endothelium in the blood vessels is thought to be the major target for graft rejection. Endothelial cells of a transplanted organ are believed to remain of donor origin after transplantation. We aimed to verify this concept. METHODS: We studied biopsy samples from 12 renal transplants for the presence of endothelial cells of recipient origin. We used three different techniques: immunohistochemistry for MHC class-I antigens, immunohistochemistry for ABO-blood-group antigens, and in-situ hybridisation for X and Y chromosomes. After we had confirmed that these techniques did identify endothelial cells of recipient origin, tests were done in a second group of 26 patients to find out whether endothelial chimerism correlated with graft rejection. FINDINGS: We found a strong correlation between the percentage of recipient endothelial cells in the peritubular capillaries and the type of graft rejection (r = 0.71, p < 0.0001). These cells were found mainly in grafts of patients who had had rejection, especially among patients with vascular rejection. In grafts of patients without rejection only sporadically recipient endothelial cells were detectable. INTERPRETATION: Our data show that endothelial cells of the recipient can replace those of the donor. This replacement is associated with graft rejection. We postulate that endothelium that is damaged by vascular rejection is repaired by endothelial cells of the recipient. PMID- 11197361 TI - Resistance of t(11;18) positive gastric mucosa-associated lymphoid tissue lymphoma to Helicobacter pylori eradication therapy. AB - 20-30% of gastric mucosa-associated lymphoid tissue (MALT) lymphoma associated with Helicobacter pylori do not regress after antibiotic therapy. Regression can be assessed only by extended follow-up. To assess whether t(11;18, q21;q21), which results in a chimeric transcript between the AP12 and MLT genes, predicts lymphoma resistance to antibiotic therapy, we screened for the fusion transcript with RT-PCR in ten responsive and 12 non-responsive gastric MALT lymphomas. The AP12-MLT transcript was detected in nine (75%) of 12 patients non-responsive to antibiotic therapy but not in responsive patients. Most H pylori-associated gastric MALT lymphomas that do not respond to antibiotic therapy are associated with t(11;18, q21;q21). PMID- 11197362 TI - Sunlight "D"ilemma: risk of skin cancer or bone disease and muscle weakness. PMID- 11197363 TI - Effect of vancomycin and rifampicin on meticillin-resistant Staphylococcus aureus biofilms. AB - Decolonisation of patients with urinary catheter colonisation by meticillin resistant Staphylococcus aureus (MRSA) is often difficult. Replacement of the catheter after prophylactic vancomycin administration has been one approach that is often unsuccessful in clinical practice. We suspected that formation of MRSA biofilms might account for the persistence of infection, and our study confirms this, also showing that MRSA is able to colonise a silastic rubber surface even in the presence of prophylactic vancomycin or rifampicin. PMID- 11197364 TI - Multidrug-resistance protein 1 in focal cortical dysplasia. AB - Drug resistance in epilepsy is poorly understood. We used routine immunohistochemistry to assess overexpression of a multidrug-resistance protein in dysplastic neurons, glia, and around vessels in surgically resected epileptogenic human brain tissue. We showed non-tumoral overexpression of this multidrug-resistance protein, which might contribute to drug resistance in epilepsy caused by focal cortical dysplasia. PMID- 11197365 TI - Treatment of aplastic anaemia with granulocyte-colony stimulating factor and risk of malignancy. Italian Aplastic Anaemia Study Group. AB - Granulocyte-colony stimulating factor (G-CSF) is being increasingly used in healthy volunteers to harvest haemopoietic stem cells. A possible role of G-CSF in the development of clonal disorders or leukaemia has been suggested. We analysed 144 patients with aplastic anaemia treated with immunosuppression protocols with or without G-CSF, with normal cytogenetics at diagnosis or immediately after immunosuppression. Our findings indicated that the risk of developing myelodysplasia or leukaemia was similar in patients with aplastic anaemia on immunosuppressive treatment with or without G-CSF. Therefore, it seems unlikely that G-CSF causes leukaemia in healthy volunteers. PMID- 11197366 TI - Aid organisations rebuke UN for Afghanistan sanctions. PMID- 11197367 TI - Music tunes up memory in dementia patients. PMID- 11197368 TI - Robert Butler: championing a healthy view of ageing. PMID- 11197369 TI - "Blood heads" and AIDS haunt China's countryside. PMID- 11197370 TI - New injuries for Kashmir as tentative steps towards peace are taken. PMID- 11197371 TI - "Plan Colombia"--parallels drawn with Vietnam war. PMID- 11197372 TI - Pathogenesis and genetics of pre-eclampsia. AB - After more than a century of intensive research, pre-eclampsia and eclampsia remain an enigmatic set of conditions. Aberration of the interaction between placental and maternal tissue is probably the primary cause, but the exact nature of the differences from normal pregnancy remain elusive. In this review attempts to understand the sequence of physiological changes have concentrated on vascular endothelium and oxidative stress issues. There are genetic components to susceptibility, but the relative contributions of maternal and fetal genotypes are still unclear. Whole-genome mapping could ultimately define the causative genes. PMID- 11197373 TI - Defining and refining international donor support for combating the AIDS pandemic. AB - The international aid effort against AIDS is greatly incommensurate with the severity of the epidemic. Drawing on the data that international aid donors self reported to the Organization for Economic Cooperation and Development (OECD), we find that, between 1996 and 1998, finance from all rich countries to sub-Saharan Africa for projects designated as AIDS control averaged US $69 million annually, and, assuming a safe margin for under-reporting and misreporting, we estimate that total donor spending on HIV/AIDS control was perhaps twice that at most. Since the late 1980s, aid levels have dropped relative to the prevalence of HIV infection, and stood recently at about $3 per HIV-infected person. Lack of finance is now the primary constraint on progress against AIDS, notwithstanding the widespread belief that a lack of interest from the goveements of poor countries is limiting. We argue that to produce a meaningful response to the pandemic, international assistance must be based on grants, not loans, for the poorest countries; be increased within the next 3 years to a minimum of $7.5 billion or more; be directed toward funding projects which are proposed and desired by the affected countries themselves, and which are judged as having epidemiological merit against the pandemic by a panel of independent scientific experts; and fund concurrent needs, including prevention, drug treatment (such as highly active antiretroviral therapy), and blocking mother-to-child HIV transmission. An effort of this scope and scale will both radically alter the prospects for intervention against AIDS in poor countries, and together with comparable efforts to control other infectious diseases, is easily afforded by the OECD donor economies, whose aggregate national income recently surpassed $21 trillion annually. PMID- 11197374 TI - Renal failure after bone-marrow transplantation. PMID- 11197375 TI - Concealing medication in patients' food. PMID- 11197376 TI - Tamoxifen and risk of endometrial cancer. PMID- 11197377 TI - Tamoxifen and risk of endometrial cancer. PMID- 11197378 TI - Tamoxifen and risk of endometrial cancer. PMID- 11197379 TI - Tamoxifen and risk of endometrial cancer. PMID- 11197380 TI - Tamoxifen and risk of endometrial cancer. PMID- 11197381 TI - Tamoxifen and risk of endometrial cancer. PMID- 11197382 TI - Tamoxifen and risk of endometrial cancer. PMID- 11197383 TI - Viraemia and faecal shedding of HEV in symptom-free carriers. PMID- 11197384 TI - Public health and air pollution. PMID- 11197385 TI - Importance of differentiating health status from quality of life. PMID- 11197386 TI - Public health and air pollution. PMID- 11197387 TI - Public health and air pollution. PMID- 11197388 TI - Survival after liver transplantation. PMID- 11197389 TI - Headache angina. PMID- 11197390 TI - Origin of AIDS. PMID- 11197391 TI - Origin of AIDS. PMID- 11197392 TI - Origin of AIDS. PMID- 11197393 TI - Non-communicable disease in sub-Saharan Africa. PMID- 11197394 TI - Floating kidney. PMID- 11197395 TI - Withholding and withdrawal of life support in intensive-care units in France: a prospective survey. French LATAREA Group. AB - BACKGROUND: In France, there are no guidelines available on withholding and withdrawal of life-sustaining treatments, and information on the frequency of such decisions is scarce. METHODS: We undertook a prospective 2-month survey in 113, of a total of 220, intensive-care units (ICUs) in France to study the frequency of, and processes leading to, decisions to withhold and withdraw life sustaining treatments. FINDINGS: Life-supporting therapies were withheld or withdrawn in 807 (11.0%) of 7309 patients (withholding in 336 [4.6%] and withdrawal in 471 [6.4%], preceded in 358 by withholding). Of 1175 deaths in ICU, 628 (53%) were preceded by a decision to limit life-supporting therapies. Futility and poor expected quality of life were the most frequently cited reasons. Decisions were strongly correlated with the simplified acute physiological score, but an independent centre effect persisted after adjustment for this score. Decisions were mostly taken by all the ICU medical staff, with (54%) or without (34%) the nursing staff; however, a single physician made decisions in 12% of cases. The patient's family was involved in the decision making process in 44% of cases. The patient's willingness to limit his or her own care was known in only 8% of the cases; only 0.5% of the patients were involved in decisions. INTERPRETATION: Withholding and withdrawal of life-support therapies are widely practised in French ICUs, despite their prohibition by the French legislation. The lack of an official statement from French scientific bodies may explain several limitations on the various steps of the decision making process. PMID- 11197396 TI - The genetics of haemostasis: a twin study. AB - BACKGROUND: The concentrations of fibrinogen, factor VII and VIII, von Willebrand factor, plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator have been associated with coronary-heart disease. In addition, polymorphisms in the genes coding for fibrinogen, factor VII, PAI-1, and factor XIII have been reported to affect both protein concentrations and cardiovascular disease risk. METHODS: We did a classic twin study to assess heritabilities of these haemostatic factors. We enrolled 1002 female twins; 149 pairs of monozygotic and 352 pairs of dizygotic twins. 89 monozygotic and 196 dizygotic twin pairs were analysed for factor VII. FINDINGS: Quantitative genetic model fitting showed that genetic factors contributed to about 41-75% of the variation in concentrations of fibrinogen, factor VII, factor VIII, PAI-1, tissue plasminogen activator, factor XIII A-subunit and B-subunit, and von Willebrand factor. Factor XIII activity showed higher (82%) and factor XIIa lower (38%) heritability. INTERPRETATION: We have shown that genetic factors have a major effect on plasma concentrations of haemostatic proteins. Our results stress the importance of research into the genetic regulation of proteins involved in haemostasis and atherothrombotic disorders, including myocardial infarction and stroke. PMID- 11197397 TI - Quality of hospital care for seriously ill children in less-developed countries. AB - BACKGROUND: Improving the quality of care for sick children referred to hospitals in less-developed countries may lead to better outcomes, including reduced mortality. Data are lacking, however, on the quality of priority screening (triage), emergency care, diagnosis, and inpatient treatment in these hospitals, and on aspects of these potential targets that would benefit most from interventions leading to improved health outcomes. METHODS: We did a qualitative study in 13 district hospitals and eight teaching hospitals in seven less developed countries. Experienced paediatricians used a structured survey instrument to assess initial triage, emergency and inpatient care, staff knowledge and practices, and hospital support services. FINDINGS: Overall quality of care differed between countries and among hospitals and was generally better in teaching hospitals. 14 of 21 hospitals lacked an adequate system for triage. Initial patient assessment was often inadequate and treatment delayed. Most emergency treatment areas were poorly organised and lacked essential supplies; families were routinely required to buy emergency drugs before they could be given. Adverse factors in case management, including inadequate assessment, inappropriate treatment, and inadequate monitoring occurred in 76% of inpatient children. Most doctors in district hospitals, and nurses and medical assistants in teaching and district hospitals, had inadequate knowledge and reported practice for managing important childhood illnesses. INTERPRETATION: Strengthening care for sick children referred to hospital should focus on achievable objectives with the greatest potential benefit for health outcome. Possible targets for improvement include initial triage, emergency care, assessment, inpatient treatment, and monitoring. Priority targets for individual hospitals may be determined by assessing each hospital. PMID- 11197398 TI - Long-term prospective observational study of patients with peanut and nut allergy after participation in a management plan. AB - BACKGROUND: Peanut and nut allergy is common and the most frequent cause of severe or fatal reactions to foods. Current advice is poor--doctors give an epinephrine injector to patients, without training or advice on nut avoidance--so that further reactions are common and deaths occur. We devised and assessed a management programme providing advice on nut avoidance and emergency medication. METHODS: Unselected referrals with confirmed peanut or tree-nut allergy were recruited. Severity of nut allergy was graded 1-5 and emergency medication allocated accordingly: oral antihistamine with or without inhaled or injected epinephrine. Patients, parents, and school staff received verbal and written advice on nut avoidance as well as training in recognition and self-treatment of reactions, with a written treatment plan. At follow-up (more than 13610 patient months) retraining was given and details of further reactions obtained. FINDINGS: 88 (15%) of 567 patients had a follow-up reaction of reduced severity. 62 of 88 were mild (grades 1-3, mainly cutaneous) and 49 patients used oral antihistamine, six inhaled adrenaline, and ten took no treatment. 12 of 12 patients with a moderate follow-up reaction improved after inhaled epinephrine. Only three (0.5%) of 567 patients, aged 27-40 years, had a severe follow-up reaction (involving dyspnoea) compared with 12% initially. Only one of 567 changed from a mild index reaction to a severe follow-up reaction. Patients with a moderate/severe (grade 4 5) reaction were older (median 18 years vs 9 years; p=0.03) and nine of 26 received injected epinephrine which was always effective. 85% of patients had no further reactions. Severity was related to the amount of nut eaten. INTERPRETATION: Self-treatment was effective (inhaled epinephrine for early laryngeal oedema and an epinephrine injector for severe reactions) but provision of this treatment, including who should carry epinephrine, required assessment of allergy severity. Our management plan was effective, and our results indicate that patients should be referred to specialist allergy centres for advice on nut avoidance. PMID- 11197399 TI - The pituitary gland and hereditary haemochromatosis. PMID- 11197400 TI - A 25-year-old with severe coronary artery disease. PMID- 11197401 TI - Long-term propofol infusion and cardiac failure in adult head-injured patients. AB - Five adult patients with head injuries inexplicably had fatal cardiac arrests In our neurosurgical intensive-care unit after the introduction of a sedation formulation containing an increased concentration of propofol. To examine the possible relation further, we did a retrospective cohort analysis of head-injured adults admitted to our unit between 1996 and 1999 who were sedated and mechanically ventilated. 67 patients met the inclusion criteria, of whom seven were judged to have died from propofol-infusion syndrome. The odds ratio for the occurrence of the syndrome was 1.93 (95% CI 1.12-3.32, p=0.018) for every mg/kg per h increase in mean propofol dose above 5 mg/kg per h. We suggest that propofol infusion at rates higher than 5 mg/kg per h should be discouraged for long-term sedation in the intensive-care unit. PMID- 11197402 TI - Inhaled nitric oxide in neonates with persistent pulmonary hypertension. AB - To investigate the oxygenation and haemodynamic dose response to inhaled nitric oxide in neonates with persistent pulmonary hypertension (PPHN), we gave seven neonates nitric oxide and measured directly pulmonary arterial pressure. Inhaled nitric oxide produced peak improvement in oxygenation at 5 parts per million (ppm) whereas peak improvement in the pulmonary-to-systemic arterial pressure ratio did not occur until a nitric oxide dose of 20 ppm, which suggests that an Initial dose of 20 ppm is optimum for the treatment of PPHN. PMID- 11197403 TI - Mifepristone abortion outside the urban research hospital setting in India. AB - Medical abortion holds great promise in less-developed countries, where abortion morbidity and mortality remain high. We tested the French mifepristone misoprostol regimen in two urban outpatient family-planning clinics (n=600) and a rural hospital (n=300) in India. 4% of urban women and 1% of rural women were lost to follow-up. Perfect use and typical-use success rates were as high as European rates at all sites. Although rural women reported fewer side-effects, most women in urban and rural settings were satisfied with their medical abortions. Medical abortion can be offered safely, effectively, and acceptably in urban outpatient clinics and rural hospitals in India. PMID- 11197404 TI - Sentinel-node biopsy in axillary lymph-node staging for patients with multicentric breast cancer. AB - Multicentric breast cancer is thought to be a contraindication for sentinel-node biopsy by most clinicians. In a prospective study we took sentinel-node biopsy samples from 19 patients with multicentric invasive breast cancer with use of a blue dye and radiolabelled colloid mapping technique at the subareolar injection site. All patients underwent complete axillary dissection after sentinel-node biopsy. Nine patients had tumour-free and ten had metastatic sentinel nodes. The sentinel-node status was in concordance with the axillary sample in all patients. Sentinel-node biopsy might become an alternative to complete axillary dissection in patients with multicentric breast cancer with clinically negative lymph nodes. PMID- 11197405 TI - Audit further exposes UK's worst serial killer. PMID- 11197406 TI - Elusive platelet ADP receptor identified. PMID- 11197407 TI - Should stress carry a health warning? PMID- 11197408 TI - Bush picks Wisconsin governor for key health post. PMID- 11197409 TI - US mental health care services failing children, report says. PMID- 11197410 TI - Nigerian government investigates Pfizer drug trial allegations. PMID- 11197411 TI - Paris' Pompidou hospital plagued by setbacks. PMID- 11197412 TI - Alternative strategies suggested to eradicate "hidden hunger" in India. PMID- 11197413 TI - Blood-pressure measurement and classification in pregnancy. AB - Pre-eclampsia is usually defined on the basis of new onset hypertension and albuminuria developing after 20 weeks of pregnancy. There are difficulties with measurement of these variables. Conventional sphygmomanometry remains the gold standard for blood-pressure measurement. The value of ambulatory blood-pressure measurement has yet to be established. Oedema is now omitted from all definitions of preeclampsia, although the finding of widespread severe oedema of sudden onset should not be ignored for clinical purposes. Definitions of pre-eclampsia based solely on hypertension and proteinuria ignore the wide clinical variability in this syndrome. Women with no proteinuria but who do have hypertension and other features such as severe headache or other symptoms, thrombocytopenia, hyperuricaemia, disordered liver function, and fetal compromise are likely to have pre-eclampsia. This notion is accepted in the new Australasian definition of pre-eclampsia and more than hinted at in the new American College of Obstetricians and Gynecologists' definition. Definitions used for clinical purposes should be as safe as practical; they are likely to include a considerable number of false positives. Most research studies are weakened if patients without the disease are included. Therefore, a separate stringent research definition of pre-eclampsia we also suggest. PMID- 11197414 TI - Suicide of the nephron. AB - There are various causes of renal disease. However, progressive renal disease is closely linked to the degree and duration of proteinuria. At first sight, this seems a perverse response in which a compromised organ unleashes a coordinated series of reactions that exacerbate the damage already done. Although the nephron has mechanisms whereby it can compensate for damage both by hypertrophy and hyperfunction after renal injury or ablation, these changes seem to provide only a temporary compensation. I and my colleagues found altered renal telomere shortening in the male rat linked to increased or decreased proteinuria and longevity, which suggests a mechanism whereby this compensatory process may be limited. I hypothesise that when the damaging or hypertrophic processes shorten renal telomeres to a critical length, the cells senesce with loss of function. I also suggest that the complex series of responses triggered in a protein-leaking nephron is normally a beneficial and limited process. It leads to the replacement by fibrosis of a malfunctioning unit in an otherwise healthy organ that has substantial spare capacity. The response only becomes life threatening when there is widespread nephron damage, the acceleration of which results in the ablation of all nephron function. PMID- 11197415 TI - Anderson-Fabry's disease: alpha-galactosidase deficiency. PMID- 11197416 TI - Uses of error: clinical and epidemiological. PMID- 11197417 TI - Mother-to-child HCV transmission. PMID- 11197418 TI - Mother-to-child HCV transmission. PMID- 11197419 TI - Mother-to-child HCV transmission. PMID- 11197420 TI - Mother-to-child HCV transmission. PMID- 11197421 TI - Mother-to-child HCV transmission. PMID- 11197422 TI - Cystatin for estimation of glomerular filtration rate. PMID- 11197423 TI - Voluntary counselling and testing for HIV-1. PMID- 11197424 TI - Voluntary counselling and testing for HIV-1. PMID- 11197425 TI - Diagnosis of meningococcal septicaemia. PMID- 11197426 TI - Diagnosis of meningococcal septicaemia. PMID- 11197427 TI - Diuretic response to water loading. PMID- 11197428 TI - Care for stroke patients. PMID- 11197429 TI - Care for stroke patients. PMID- 11197430 TI - The idea and the experiment. PMID- 11197431 TI - The idea and the experiment. PMID- 11197432 TI - Conjoined twins. PMID- 11197433 TI - Research in complex emergencies. Medical Emergency Relief International. PMID- 11197434 TI - Informed consent is flawed. PMID- 11197435 TI - Research agenda in less-developed countries. PMID- 11197436 TI - Accuracy of references in theses. PMID- 11197437 TI - Will India's medical sites learn from the US experience? PMID- 11197438 TI - The real lessons from Harold Frederick Shipman. PMID- 11197439 TI - Genetics of haemostasis. PMID- 11197440 TI - Aspirin for primary prevention of cardiovascular events. PMID- 11197441 TI - Relation between dermatomyositis and polymyositis and cancer. PMID- 11197442 TI - Paediatric emergency care in developing countries. PMID- 11197443 TI - Management of peanut and nut allergies. PMID- 11197444 TI - We all make mistakes: tell us yours. PMID- 11197445 TI - Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Collaborative Group of the Primary Prevention Project. AB - BACKGROUND: In addition to the treatment of specific cardiovascular risk factors, intervention which interferes with the general mechanisms of atherosclerosis could further reduce the incidence of cardiovascular events. We aimed to investigate in general practice the efficacy of antiplatelets and antioxidants in primary prevention of cardiovascular events in people with one or more major cardiovascular risk factors. METHODS: We did a randomised controlled open 2x2 factorial trial to investigate low-dose aspirin (100 mg/day) and vitamin E (300 mg/day) in the prevention of cardiovascular events, in people with one or more of the following: hypertension, hypercholesterolaemia, diabetes, obesity, family history of premature myocardial infarction, or individuals who were elderly. FINDINGS: 4495 people (2583 female, mean age 64.4 years) were included in the trial. After a mean follow-up of 3.6 years the trial was prematurely stopped on ethical grounds when newly available evidence from other trials on the benefit of aspirin in primary prevention was strictly consistent with the results of the second planned interim analysis. Aspirin lowered the frequency of all the endpoints, being significant for cardiovascular death (from 1.4 to 0.8%; relative risk 0.56 [95% CI 0.31-0.99]) and total cardiovascular events (from 8.2 to 6.3%; 0.77 [0.62-0.95]). Severe bleedings were more frequent in the aspirin group than the no-aspirin group (1.1% vs 0.3%; p<0.0008). Vitamin E showed no effect on any prespecified endpoint. Analyses were by intention-to-treat. INTERPRETATION: In women and men at risk of having a cardiovascular event because of the presence of at least one major risk factor, low-dose aspirin given in addition to treatment of specific risk factors contributes an additional preventive effect, with an acceptable safety profile. The results on vitamin E's cardiovascular primary preventive efficacy are not conclusive per se, although our results are consistent with the negative results of other large published trials on secondary prevention. PMID- 11197446 TI - Frequency of specific cancer types in dermatomyositis and polymyositis: a population-based study. AB - BACKGROUND: Dermatomyositis and polymyositis are associated with cancer, but previous nationwide studies have not had sufficient cases to test the association between myositis and specific cancer types. Our aim was to investigate the risk of specific cancer types in individuals with dermatomyositis and polymyositis. METHODS: We did a pooled analysis of published national data from Sweden, Denmark, and Finland. All patients with dermatomyositis and polymyositis (> or =15 years old) were identified by discharge diagnosis from the Swedish National Board of Health (1964-83), Danish Hospital Discharge Registry (1977-89), and Finnish National Board of Health (1969-85). Personal details were matched to national cancer registries, to identify all cases of cancer up to 1987 in Sweden, 1995 in Denmark, and 1997 in Finland, and to national death registries for the same periods. We calculated standardised incidence ratios (SIR) for individual cancer sites for dermatomyositis and polymyositis separately, using national cancer rates by country, sex, age, and date. FINDINGS: We identified 618 cases of dermatomyositis, of whom 198 had cancer. 115 of the 198 developed cancer after diagnosis of dermatomyositis. This disease was strongly associated with malignant disease (SIR 3.0, 95% CI 2.5-3.6), particularly ovarian (10.5, 6.1-18.1), lung (5.9, 3.7-9.2), pancreatic (3.8, 1.6-9.0), stomach (3.5, 1.7-7.3), and colorectal (2.5, 1.4-4.4) cancers, and non-Hodgkin lymphoma (3.6, 1.2-11.1). 137 of the 914 cases of polymyositis had cancer, which developed after diagnosis of polymyositis in 95. Polymyositis was associated with a raised risk of non-Hodgkin lymphoma (3.7, 1.7-8.2), and lung (2.8, 1.8-4.4) and bladder cancers (2.4, 1.3-4.7). In both dermatomyositis and polymyositis, risk of malignant disease was highest at time of myositis diagnosis. INTERPRETATION: Our results provide evidence that dermatomyositis is strongly associated with a wide range of cancers. The overall risk of malignant disease is also modestly increased among patients with polymyositis, with an excess for some cancers. PMID- 11197447 TI - Oedema in childhood. AB - Oedema is a common childhood problem with important public health implications. It is an abnormal accumulation of fluid in the interstitial space which might result from a decrease in intravascular oncotic pressure, an increase in intravascular hydrostatic pressure, an increase in capillary permeability or impaired lymphatic drainage. Renal sodium retention is an important factor in generalised oedema. This article reviews the pathophysiology and aetiology of oedema in children and suggests an approach to evaluation, diagnosis and management of the problem. PMID- 11197448 TI - Urinary tract infection in children: a review of its pathogenesis and risk factors. AB - Urinary tract infection (UTI) is one of the commonest bacterial infections seen in children, ranking second only to those of the respiratory tract. A steady flow of urine, complete emptying of the bladder and various host defences provide the principal means of protection. Urinary stasis, on the other hand, provides an opportunistic environment for bacterial multiplication; several other factors also contribute to UTI, such as urinary obstruction, vesico-ureteric reflux (VUR) and other urinary tract malformations. UTI, especially in the presence of VUR, may lead to scarring of the kidney and progressive renal disease. It is vital, therefore, to diagnose such anomalies at an early stage, the overall aim being to identify those at high risk so that measures may be taken to prevent serious complications and preserve renal function. Those at low risk of UTI, however, should not be over investigated; this is in order to keep invasive procedures down to a minimum. Whenever possible, the management of high risk cases is best discussed between paediatrician, microbiologist, radiologist, urologist and the general practitioner. PMID- 11197449 TI - Dietary advice on cancer prevention: time for a change? AB - Media coverage of recent dietary intervention studies has cast doubt on dietary advice for cancer prevention. The studies cited focussed on colorectal adenoma initiation as opposed to progression. There is ample evidence that in the colorectum the factors controlling initiation of adenomas differ from those causing progression to cancer, and that it is the latter that are the most important. In the light of this it is argued that studies of adenoma initiation are irrelevant to the advice given for overall cancer prevention. PMID- 11197450 TI - The use of anthropometric and clinical parameters for early identification and categorisation of nutritional risk in pre-school children in Benin City, Nigeria. AB - This study was conducted in Benin City, Nigeria between June and August 1996 to assess nutritional status and health risks of three to five-year-old children, with the view to suggesting practical approaches to their early detection and intervention. A total of 165 children comprising 90 males and 75 females was studied. Mid-upper arm circumference (MUAC), weight-for-age (WFA), weight-for height (WFH) and height-for-age (HFA) z-scores were determined and used to calculate percentage prevalence of malnutrition. Clinical features of macro- and micro-nutrient deficiency were used to develop a clinical scoring system which was subsequently matched with anthropometric z-scores. The results showed that MUAC z-scores (-1.91 SD +/- 0.74) gave the highest percentage prevalence of malnutrition of 45.2% in this population, followed by the WFA (-1.22 SD +/- 1.07) and HFA (-0.84 SD +/- 1.42) z-scores with a percentage prevalence of 23.3% and 20.6% respectively. The WFH z-score (-0.89 SD +/- 1.06) was the least sensitive in detecting malnutrition (14.7% prevalence). The percentage prevalence calculated from MUAC z-scores matched FAO figures (43%) for the sub-Saharan African region in 1996. MUAC z-scores also correlated more closely with the clinical features of malnutrition (R2 = 0.7087). Progressively worsening clinical features were also seen with decreasing z-scores for all variables. Even though moderate differences in clinical and anthropometric variables were detected between the sexes with females fairing better than male subjects, these differences were not statistically significant. Comparisons between anthropometric variables showed only weak correlation, except for WFA vs. HFA z scores (R2 = 0.5233) and WFH vs. WFA z-scores (R2 = 0.4559) which showed moderately positive correlation. We conclude that whereas MUAC z-scores were most sensitive in detecting the extent of malnutrition in this population, merely using anthropometric variables alone may lead to significant under-reporting of the prevalence of malnutrition in a community. A combination of various anthropometric z-scores with clinical features will however help in the early identification and categorisation of subjects in terms of degree of nutritional risk. The training of field health and nutrition workers should therefore emphasise the routine use and combination of anthropometric and clinical variables in the determination of prevalence of malnutrition and in the formulation of intervention strategies for nutrition rehabilitation. PMID- 11197451 TI - Is childhood allergy more common amongst an island population? AB - A rise in the prevalence of childhood asthma has been reported in both the UK and in several overseas countries during recent years. Wide geographical variations have also been demonstrated in the distribution of hay fever, atopic eczema and other allergic symptoms. It is the impression of many parents and some clinicians that allergic symptoms may be even higher amongst children in an island environment compared with a similar population on the mainland. To test this hypothesis, Guernsey and Jersey in the Channel Islands, and the Isle of Man in the Irish Sea participated as an independent arm in the International Study of Asthma and Allergy in Childhood (ISAAC). This entailed self-completion of a 38 part pretested and validated questionnaire in a classroom setting under standardised conditions. A total of 3,772 secondary students in school years eight and nine living in the three islands were compared with 27,507 students of similar age in 93 British secondary schools enrolled in the larger UK study. There are a number of demonstrable differences in climate, home environment and lifestyle factors between the islands and mainland UK. Although results were generally above the UK mean, they were comparable with the reference region of South West England and invariably below the UK maximum. For instance, the prevalence of 'ever wheezed?', 'wheezed in last twelve months?', 'wheezed with exercise?' and 'diagnosis of asthma' were a mean of 50.5%, 34.5%, 31% and 19.7% in the islands compared with a UK prevalence of 48.8%, 33.3%, 28.5% and 20.7%, whilst the prevalence of 'runny nose ever?' and 'runny nose in last twelve months?' was a mean of 46.6% and 36.7% in the islands, compared with 47.1% and 37.9% in the UK mean. These differences were not statistically significant. This information will be reassuring to parents of island children, and also demonstrates that services for the management of asthma and other allergic conditions should not be a higher public health priority in these locations than on the mainland of Britain. PMID- 11197452 TI - Dietary fibre, physicochemical properties and their relationship to health. AB - Dietary carbohydrates that escape digestion and absorption in the small intestine include non-digestible oligosaccharides (carbohydrates with a degree of polymerisation between three and ten), resistant starch and non-starch polysaccharides. The physiological effects of this heterogeneous mixture of substrates are partly predictable on the basis of their physicochemical properties. Monosaccharide composition and chain conformation influence the rate and extent of fermentation. Water-holding capacity affects stool weight and intestinal transit time. Viscous polysaccharides can cause delayed gastric emptying and slower transit through the small bowel, resulting in the reduced rate of nutrient absorption. Polysaccharides with large hydrophobic surface areas have potentially important roles in the binding of bile acids, carcinogens and mutagens. Ispaghula is capable of binding bile acids through a large number of weak binding sites on the polysaccharide structure, and having greatest effect on the potentially more harmful secondary bile acids deoxycholic acid and lithocholic acid. PMID- 11197453 TI - Do Asians with diabetes in Sandwell receive inferior primary care? A retrospective cohort study. AB - Although diabetes is more prevalent among Asian people, Asians with diabetes are anecdotally believed to receive a lesser standard of care, compared with non Asians. The aim of this study was to evaluate whether Asian patients with diabetes in Sandwell receive an inferior standard of care in primary care compared with non-Asians. Standards were based on tests carried out, in compliance with Sandwell's Diabetes Local Clinical Guideline. Data were collected from records of 774 patients with diabetes in 14 Sandwell practices. Proportions were recorded of Asian patients receiving specified tests, compared with non Asians. No significant differences were observed between Asians and non-Asians for checks on feet, eyes, body mass index (BMI), smoking or blood pressure. Significantly fewer Asians received an HbA1c check. The mean HbA1c value was higher in Asians. More Asian patients received a urine test than non-Asians. Asian patients generally had lower BMI values. When stratified by practice however, no significant differences between Asians and non-Asians were observed for any single check. No significant differences were found between the overall proportions of checks carried out between Asians and non-Asians. A wide variation was observed in the proportion of patients who had individual checks done, between practices. There were no systematic differences in the standard of care given to Asian and non-Asian patients. Practices varied a great deal in the extent to which they carry out, and record, checks on patients with diabetes. A possible explanation for the reason that no summary result showed a significant difference was due to the confounding effect of the practice: that general practices tended to treat all their patients--Asian and non-Asian--similarly. Nevertheless, general practitioners should therefore take steps to ensure that all patients with diabetes have these checks at recommended intervals. PMID- 11197454 TI - Medicine 2000 years ago: the case of Qumran and other biblical sites. AB - Since the eighteenth century, the dominance of orthodox or allopathic medicine in the West led to the branding of other forms of medicine as alternative. However, research shows a narrowing in the gap in popularity of the two methods and it is possible to envision a time when alternative medicine and mainstream medicine will work in tandem. As the West completes a year of millennium celebrations and looks back to the events that shaped the founding of the first millennium two thousand years ago, it is appropriate to increase our understanding of the form medicine took at that time. Research on Qumran and other biblical sites shows that the therapies offered there were based on alternative therapies such as herbal medicine and hydrotherapy as well as conventional therapy such as surgery. The article shows that the twin reliance on alternative and orthodox methods emerging today, marks a return to a pattern of provision which prevailed at the time the first millennium was born. PMID- 11197455 TI - Extramedullary plasmacytoma presenting as upper back pain. AB - Extramedullary plasmacytoma (EMP) is a rare soft tissue plasma cell tumour, usually presenting as a mass within the upper respiratory tract. It is most unusual for it to present in the posterior mediastinum as a primary solitary lesion. Discussed here is the case report of a patient who initially presented with musculoskeletal pain. Subsequent investigations, however, revealed the cause to be an EMP; diagnosis was made on finding aggregates of plasma cells on histological examination of the tissue specimen. The latter had been obtained by way of a computerised tomography scan guided biopsy of the tumour. Bone marrow aspiration studies showed no evidence of multiple myelomatosis. There was significant clinical improvement in response to radiotherapy. It is possible that this might represent one of the first documented reports of a primary solitary EMP in the posterior mediastinum. PMID- 11197457 TI - Future of the Web. PMID- 11197456 TI - A secondary interpretation is needed on serum CA 125 levels in case of serosal involvement. PMID- 11197458 TI - An overview of EPA regulation of the safe disposal of transuranic waste at the Waste Isolation Pilot Plant. AB - In March of 1999, the Waste Isolation Pilot Plant (WIPP) in southeast New Mexico, the world's first deep geological repository for radioactive materials, began receiving defense-related transuranic waste. The WIPP was designed and constructed by the U.S. Department of Energy, but critical to its opening was certification by the U.S. Environmental Protection Agency that the repository complies with the radioactive waste disposal regulations set forth as environmental radiation protection standards (40 CFR Part 191) and compliance criteria (40 CFR Part 194). This paper provides a summary of the regulatory process, including the Environmental Protection Agency's waste containment, groundwater protection, and individual dose regulations for the WIPP; the Department of Energy's performance assessment and the other parts of its compliance certification application; and the Environmental Protection Agency's review and analysis of the compliance certification application and related documentation. PMID- 11197459 TI - Detection of anthropogenic radionuclides by the CA002 monitoring station for the comprehensive test ban treaty. AB - A worldwide monitoring system for radioactive aerosols is being implemented for verification of the Comprehensive Test Ban Treaty. These 80 stations will detect airborne radioactivity not only from nuclear explosions but also from other anthropogenic and natural sources. A prototype unit has been in operation since April 1996 in Vancouver, British Columbia, Canada. It is a very sensitive system and reports clear signals for natural radioactivity, including cosmogenic 7Be, and the decay products from soil exhalation of 220Rn (thoron). In addition, there have been frequent detections of anthropogenic nuclides, probably coming from three distinct facilities-a medical isotope production center, a major university hospital, and a particle accelerator laboratory--all between 1 and 2 km away from the monitoring station. This experience is discussed to sensitize health physicists to the potential uses of this publicly available information. PMID- 11197460 TI - Determination and use of the monetary values of the averted person-sievert for use in radiation protection decisions in Hungary. AB - The monetary value of the averted dose is a key element in the implementation of the optimization principle both in radiation praxis and intervention. The main concept of this principle is to select options so as to maintain exposures at a reasonable level. The feature of this concept is to look for the minimal total cost, i.e., the sum of the costs of protection and health detriment. In its publications, ICRP emphasized the need for developing models which also take into account the "subjective" aspects of health detriment in the optimization process, such as the perception of risk by individuals and the need to put more emphasis on equity in the distribution of individual doses. This paper proposes a modified alpha-value model based on CEPN's model (Centre d'Etude sur L'Evaluation de la Protection dans le Domaine Nucleaire) to put more emphasis on recently published considerations about the smaller effects of the portion of collective dose derived from small doses. The parameters of the monetary value of unit collective dose averted, which is a key element of this type of model, can be estimated by means of approaches like human capital (HC) and willingness to pay (WTP) from the point of view of economic theories. The present study summarizes the results achieved by WTP among the radiation specialists mainly from the Paks Nuclear Power Plant, Hungary. The aim of the effort was to determine the value of a statistical life and the monetary value of a unit person-sievert associated with averted occupational exposure due to ionizing radiation. To apply the WTP method, a questionnaire has been prepared on the basis of the one introduced by CEPN in the late 1990's. The investigations show that the value of US$6,200 person-Sv(-1) seems to be acceptable for the alphabase-value for the occupational situation in Hungary in 1999. WTP assessments should be applied with caution since the economic level of the country, the workplace surveyed, and the computational methods affect the results. In addition, achieving a high level safety culture must rely on international cooperation both from the theoretical and practical viewpoints, and international markets affect the associated costs. Therefore the monetary requirements cannot always be assessed solely on a national basis. PMID- 11197461 TI - Methodology of radon monitoring and dose estimates in Postojna Cave, Slovenia. AB - Due to the specific work regime in the Postojna Cave, which depends primarily on the daily number of visitors, and on seasonal variations in air radon concentrations, an optimal methodology for radon and progeny measurement and dose calculation was sought. The program of measurement throughout the years was optimized, and now comprises 3-mo exposures of etched-track detectors, and twice a year, 8-10-d measurements using continuous monitors. Radon concentrations range from about 500 Bq m(-3) in winter to about 6,000 Bq m(-3) in summer, and equilibrium factors range from 0.42 to 0.69 in winter and from 0.33 to 0.86 in summer. Radiation doses from radon decay products for employees in the cave were calculated according to the ICRP 65 methodology. The basic input data are radon concentrations and equilibrium factors at two selected locations in the cave and the records of the time spent by a worker in the cave. Effective doses received by employees annually ranged from 0.02 to 8.4 mSv. PMID- 11197462 TI - 222Rn emanation from uranium-glazed ceramics. AB - Orange-red uranium-glazed dinnerware was found to emanate 222Rn to produce an average of less than 0.1 Bq 222Rn decay per piece, which should have no associated health risks. Comparison of 222Rn emanation to 226Ra in glazes (measured by alpha spectrometry) indicated inefficient emanation (<5%) of 222Rn, consistent with the low radon levels observed and with the presence of 222Rn progeny in glazes. These studies also showed that reagent grade uranium compounds may emanate measurable 222Rn. PMID- 11197463 TI - Thermodiffusion in concrete slab as a driving force of indoor radon entry. AB - The core of the hypotheses considered is that there is an additional strong driving force-the thermodiffusion of radon and soil air in concrete and soils, which can cause an intensive indoor radon entry. A vertical thermogradient in the slab causes thermodiffusion air flux through concrete into the house. The proof of this concept is based on consideration of concrete slab as a micro-porous system having a pore-size distribution that mostly pertains to Knudsen's region and a transition zone of pore sizes. The Knudsen's theory for a transition zone is developed, which is consistent with the known experimental data of thermodiffusion. Calculated thermodiffusion air flux across a concrete slab under thermogradient 80 K m(-1) approximately ranges 1 x 10(-7)-1 x 10(-6) kg x m(-2) x s(-1). The calculated typical radon-bearing advective air velocity in soil due to thermogradient in the slab is about 1 x 10(-6) m x s(-1). PMID- 11197464 TI - Chromosome aberrations study of pupils in high radon level elementary school. AB - The ICRP Publication 65 recommends 200-600 Bq x m(-3) as the indoor radon action level for the general public. In Slovenia, a value of 400 Bq x m(-3) has been proposed but not yet approved. In a nation-wide radon project financed by the Health Inspectorate of Slovenia, it was discovered that the elementary school named "S3" belongs to a group of schools with elevated winter indoor radon concentrations up to 7,000 Bq x m(-3). Opening windows and doors during classes substantially decreased radon concentrations, but very seldom below 1,000 Bq x m( 3). Yearly effective doses for pupils, estimated according to ICRP 65, ranged from 7 to 11 mSv. Because the pupils have been subjected to the elevated radon concentrations, special preventive health checks have been performed. The examination protocol included mutagenetic tests, one for structural chromosomal aberrations and the other a micronucleus test. Altogether 85 pupils (37 girls and 48 boys) from the first four grades between the ages of 9 and 12 y were examined. An increase in cytogenetic damage was found for these pupils, compared to the control group, composed of pupils of the same age from another area with indoor radon concentrations in their school of below 400 Bq x m(-3). The incidence of structural chromosomal aberrations reached 2.0% (0.5-4) and micronucleus test was 6.52 per 500 cells with a maximum of 15 in some cases. In the control group structural chromosomal aberrations varied from 0.5 to 2.5%, while the maximum incidence of micronucleus was 9 micronucleus per 500 CB cells. The results obtained are preliminary and suggest a need to expand the study. A long-term radon survey, at least over a year, of the homes and wider residential environment of the pupils would be necessary to assess the correlation between radon exposure and both structural chromosomal aberrations and micronucleus findings. PMID- 11197465 TI - Effects of gadolinium on the retention and translocation of 239Pu-hydroxide. AB - The effect of gadolinium on the lung retention, excretion, and translocation of plutonium was studied in rats instilled intratracheally with plutonium hydroxide with and without gadolinium. Three types of plutonium hydroxide were prepared: pure 239Pu-hydroxide colloid, that containing a high concentration of gadolinium, and that containing a low concentration of gadolinium. The lung retention of 239Pu was higher and the fecal excretion was lower in the rats administered 239Pu hydroxide containing a high concentration of gadolinium than those administered pure 239Pu-hydroxide colloid. The translocation of 239Pu from lung to other organs including the liver, spleen, femur, and kidney was not affected by gadolinium. The cytological examination of bronchoalveolar lavage cells showed that the administration of 239Pu-hydroxide containing a high concentration of gadolinium induced the inflammatory reactions in the lung. The delayed alveolar clearance of plutonium in the rats administered 239Pu-hydroxide colloid containing a high concentration of gadolinium may be attributable to the change in physicochemical characteristics of colloid and the inflammation induced in the lung by gadolinium. PMID- 11197466 TI - Radon in public water supplies in Migdonia basin, Central Macedonia, Northern Greece. AB - The main objective of this work is the accurate measurement of radon concentration in the public water supplies of the Migdonia basin in Northern Greece. The main aim is to localize the sub-areas that present high radon concentrations in water and to inform the local authorities so that more detailed studies might be set up in these areas. About 80 samples from special bore holes and taps that supply the local population with fresh water were collected in order to obtain detailed radon measurements. For the analyses, a liquid scintillation counting system, using the Packard protocol for measuring radon in water, was employed. The results of the investigation show that radon concentrations in these public water supplies are significant. The concentrations ranged from background concentrations to 170 Bq x L(-1). The level of 50 Bq x L( 1) is exceeded in 23% of water supplies. These preliminary results with initial data interpretation and inter-comparison assessment are presented. These results of the analyses showed that elevated radon concentrations were detected in water samples from an area at the western part of the Lake Volvi, due probably to the local intense tectonism, and from a village above the Lake Koronia. PMID- 11197467 TI - Temperature dependence of adsorption coefficients of 222Rn on activated charcoal determined by adsorption-desorption method. AB - Adsorption coefficients of 222Rn on five activated charcoal were determined (at 21, +7 and +26 degrees C) by an adsorption-desorption technique using a radon source and an Erlenmeyer flask. They varied from 1.1 to 41.2 L x g(-1). From this variation the mean heat of adsorption of radon on our charcoal was calculated as equal to 4,630(50) cal/mole. PMID- 11197468 TI - Did NATO attacks in Yugoslavia cause a detectable environmental effect in Hungary? AB - Because of the intensive NATO bombardment of the neighboring region to Hungary, i.e., Vojvodina, North Yugoslavia, air monitoring for detection of depleted uranium particles supposed to be used as a component of bullets was extended to the Southern region of the country. Alpha spectrometry was applied as a sensitive analytical technique able to detect uranium. Though no depleted uranium was detected in air by the sensitive technique of alpha-spectrometry, the increased uranium content in natural ratio as a component of normal soil, natural gas, etc., is suggested to originate from well dispersed dust (2.5 microm size) emitted to the atmosphere by explosions during bombing. This observation is supported by the geographical distribution and the relatively rapid decrease of pollution after the bomb attacks ceased. PMID- 11197469 TI - Radiographic operations and safety in the Nigerian petroleum industry. AB - This work reports on a radiation safety study of the use of radioactive sources and radiation-producing machines for radiographic purposes in the Nigerian Petroleum Industry. It is a part of a wider study on the level of safety in the use of radiation in the country-a study that covered the manufacturing and petroleum industries. The survey assessment is based on minimum requirements for radiological safety, on a scale of 0-100, to protect personnel, the public, and the environment from artificial radiation sources. The survey result shows that the level of safety in the use of radiation-emitting machines for radiographic purposes is scored at 52, while it is 66 in the use of radioisotopes. Consequently, the level of safety in radiographic practices in the Nigerian Petroleum Industry is about 60% of the ideal. PMID- 11197470 TI - Comment on article by Skedsmo and Vistnes. PMID- 11197471 TI - IAEA report to the UN. International Atomic Energy Agency. PMID- 11197472 TI - Spiers Memorial Lecture. On the hypothesis of cathodic protection of genes. PMID- 11197473 TI - Electron transfer mediated by glucose oxidase at the liquid/liquid interface. AB - In order to establish an experimental basis for exploring the reactivity of membrane-bound redox enzymes using electrochemistry at an organic/aqueous interface, the reactivity of glucose oxidase adsorbed at the dichloroethane/water interface has been studied. Turnover of glucose in the aqueous phase mediated by dimethyl ferricenium electrogenerated in the organic phase was measured by measuring the feedback current caused by recycling the mediator as the generator electrode approached close to the interface from the organic side. An unexpected self-exchange reaction of the ferrocene at the interface was suppressed by adsorption of a surfactant. The interfacial enzyme reaction could be distinguished from reaction within the bulk of the aqueous phase. Reaction within a protein-surfactant film formed at the interface is conjectured. PMID- 11197474 TI - Biomaterial engineered electrodes for bioelectronics. AB - A series of single-cysteine-containing cytochrome c, Cyt c, heme proteins including the wild-type Cyt c (from Saccharomyces cerevisiae) and the mutants (V33C, Q21C, R18C, G1C, K9C and K4C) exhibit direct electrical contact with Au electrodes upon covalent attachment to a maleimide monolayer associated with the electrode. With the G1C-Cyt c mutant, which includes the cysteine residue in the polypeptide chain at position 1, the potential-induced switchable control of the interfacial electron transfer was observed. This heme protein includes a positively charged protein periphery that surrounds the attachment site and faces the electrode surface. Biasing of the electrode at a negative potential (-0.3 V vs. SCE) attracts the reduced Fe(II)-Cyt c heme protein to the electrode surface. Upon the application of a double-potential-step chronoamperometric signal onto the electrode, where the electrode potential is switched to +0.3 V and back to 0.3 V, the kinetics of the transient cathodic current, corresponding to the re reduction of the Fe(III)-Cyt c, is controlled by the time interval between the oxidative and reductive potential steps. While a short time interval results in a rapid interfacial electron-transfer, ket1 = 20 s-1, long time intervals lead to a slow interfacial electron transfer to the Fe(III)-Cyt c, ket2 = 1.5 s-1. The fast interfacial electron-transfer rate-constant is attributed to the reduction of the surface-attracted Fe(III)-Cyt c. The slow interfacial electron-transfer rate constant is attributed to the electrostatic repulsion of the positively charged Cyt c from the electrode surface, resulting in long-range electron transfer exhibiting a lower rate constant. At intermediate time intervals between the oxidative and reductive steps, two populations of Cyt c, consisting of surface attracted and surface-repelled heme proteins, are observed. Crosslinking of a layered affinity complex between the Cyt c and cytochrome oxidase, COx, on an Au electrode yields an electrically-contacted, integrated, electrode for the four electron reduction of O2 to water. Kinetic analysis reveals that the rate limiting step in the bioelectrocatalytic reduction of O2 by the integrated Cyt c/COx electrode is the primary electron transfer from the electrode support to the Cyt c units. PMID- 11197475 TI - Engineering artificial redox chains by molecular 'Lego'. AB - This work reports on a novel approach for building artificial redox chains: the molecular 'Lego' approach. This exploits the scaffold of natural redox proteins by fusing together functional protein modules with the desired properties. The molecular 'Lego' mimics the natural molecular evolution that proceeded by modular assembly of genes/DNA segments. Non-physiological electron transfer partners, flavodoxin (fld) and cytochrome c553 (c553) from Desulfovibrio vulgaris and the haem domain of P450 BM3 (BMP) from Bacillus megaterium have been used as building blocks in different combinations to build artificial redox chains. The kinetic characterization of the electron transfer (ET) between the separate building blocks has been carried out. Under pseudo-first order conditions, a limiting ET rate, klim, of 0.48 +/- 0.05 s-1 and 43.77 +/- 2.18 s-1 and an apparent binding constant, Kapp, of 21 +/- 6 microM and 1.23 +/- 0.32 microM have been found for the fld/c553 and fld/BMP redox pairs, respectively. These results show that fld can be used as a module for transferring electrons to c553 and BMP. A 3D model of the fld/c553 and fld/BMP complexes was used to guide the construction of covalently linked assemblies via engineered disulfide bridges or by fusion of the relevant genes via an engineered loop. The first approach led to the construction, expression and characterization of the S35C and S64C mutants of fld and M23C and G51C mutants of c553. Although the redox potentials of the separate mutants were found to be the same as those of recombinant wild type proteins ( 408 mV for the semiquinone/hydroquinone couple of fld and +32 mV for the c553), the c553 homo-dimers M23C-M23C and G51C-G51C were found to have redox potentials of +88 and +105 mV, respectively. These differences have been analysed in terms of exposure of the haem cofactors to the solvent, and these lead to some interesting questions on the redox potentials of the transient redox complexes in physiological systems. The fld-c553 S64C-M23C and S35C-M23C chimeras were constructed, expressed and purified but the FMN was found to be destabilised resulting in the apo-form of these proteins. The gene fusion strategy was used to produce covalently linked assemblies of both fld-c553 and fld-BMP. The former was expressed using a seven amino acid (GPGPGPG) loop linking the C-terminus of fld to the N-terminus of c553. The fld-BMP fusion protein was successfully expressed by using the naturally occurring loop of the P450 BM3 (residues 471-479) to link the BMP domain at the N-terminus with fld domain at the C-terminus. This fusion was found to be correctly folded and functional. Efficient ET from the FMN to the haem domain (370 s-1) was also found to be in the same region of the physiological redox partners (250 s-1). This work demonstrates the feasibility of the molecular 'Lego' approach in generating functional multi-domain proteins with designed properties, beyond the restrictions imposed by the naturally occurring protein domains. PMID- 11197476 TI - A scanning tunnelling study of immobilised cytochrome P450cam. AB - A site-specifically engineered surface cysteine residue, located in a region where the haem moiety is closest to the surface, is used to anchor cytochrome P450cam enzyme molecules covalently to a gold electrode. More reproducibly ordered adsorption, at high coverage, occurs with this K344C mutant than with the wild-type enzyme. The subsequently formed close-packed monolayer arrays have been probed by scanning tunnelling microscopy under ambient conditions and under aqueous (buffered) solution at high resolution. Initial indications suggest that the immobilised enzyme is both electrochemically addressable and catalytically active. PMID- 11197477 TI - Using direct electrochemistry to probe rate limiting events during nitrate reductase turnover. AB - Protein film voltammetry of NarGH catalysing nitrate reduction under steady state conditions provides information on events occurring within the enzyme during the catalytic cycle. In this discussion we have focused on exploring the ability of two simple catalytic schemes to reproduce the voltammetric response of NarGH; electron transfer to the enzyme's active site being described either by interfacial electron exchange (Scheme 1) or intramolecular electron delivery via the operation of an electron relay centre (Scheme 2). When the two electron reduced, catalytically competent active site of the enzyme is generated from the oxidised form in 'rapid', non-rate limiting steps of the catalytic cycle, the voltammetric behaviour of NarGH cannot be reproduced. Rather under all the conditions investigated, one electron reduction of the active site from a semi reduced to a fully-reduced state is found to be crucial to progression through the enzyme's catalytic cycle. The catalytically relevant semi- and fully-reduced oxidation states of the NarGH active site are most likely to correspond to the Mo(V) and Mo(IV) states of the Mo(MGD)2 centre, respectively, although it is not possible to rule out the possibility that they correspond to molybdopterin based oxidation states as observed in other enzymes. We suggest that the rate of either conformational rearrangement within the semi-reduced active site or intramolecular electron delivery to the active site constitutes a defining feature in the catalytic cycle of NarGH and results in the napp approximately 1 appearance of the catalytic waveform. PMID- 11197478 TI - Fast voltammetric studies of the kinetics and energetics of coupled electron transfer reactions in proteins. AB - A wealth of information on the reactions of redox-active sites in proteins can be obtained by voltammetric studies in which the protein sample is arranged as a layer on an electrode surface. By carrying out cyclic voltammetry over a wide range of scan rates and exploiting the ability to poise or pulse the electrode potential between cycles, data are obtained that are conveniently (albeit simplistically) analysed in terms of plots of peak potentials against scan rate. A simple reversible electron-transfer process gives rise to a 'trumpet'-shaped plot because the oxidation and reduction peaks separate increasingly at high scan rate; the electrochemical kinetics are then determined by fitting to Butler Volmer or Marcus models. Much more interesting though are the ways in which this 'trumpet plot' is altered, often dramatically, when electron transfer is coupled to biologically important processes such as proton transfer, ligand exchange, or a change in conformation. It is then possible to derive particularly detailed information on the kinetics, energetics and mechanism of reactions that may not revealed clearly or even at all by other methods. In order to interpret the voltammetry of coupled systems, it is important to be able to define 'ideal behaviour' for systems that are expected to show simple and uncoupled electron transfer. Accordingly, this paper describes results we have obtained for several proteins that are expected to show such behaviour, and compares these results with theoretical predictions. PMID- 11197479 TI - The effect of pH and ligand exchange on the redox properties of blue copper proteins. AB - A study of the structure and redox properties of the copper site in azurins by means of EXAFS, NMR, redox titrations, potentiometry, equilibrium cyclic voltammetry and rapid scan voltammetry on protein films is reported. The results are discussed in light of existing theories on structure and function of type-1 copper sites. The exit and entry of electrons take place through the C-terminal histidine ligand of the copper. The hydrophobic patch through which this residue penetrates the protein surface plays an important role in partner docking (cf. The rim of the porphyrin ring sticking through the surface of the cytochromes-c). We find no experimental evidence for strain around the metal site. The active centre is able to maintain ET activity even in the presence of fairly gross disturbances of the site structure. The analysis of the thermodynamics of the redox reaction shows that the protein matrix and the solvent play an important role in 'tuning' the redox potential around a "design" value of around 300 mV at room temperature. The metal site appears "designed" to stabilise the Cu(II) instead of the Cu(I) form. The remarkable evolutionary success of the blue copper proteins is ascribed to the sturdy overall beta-sandwich structure of the protein in combination with a metal site that is structurally adaptable because three of its four ligands are located on a loop. The electronic "gate" that occurs in the middle of a hydrophobic patch allows for fine tuning of the docking patch for recognition purposes. PMID- 11197480 TI - Modulation of redox potential in electron transfer proteins: effects of complex formation on the active site microenvironment of cytochrome b5. AB - The reduction potential of cytochrome b5 is modulated via the formation of a complex with polylysine at the electrode surface (Rivera et al., Biochemistry, 1998, 37, 1485). This modulation is thought to originate from the neutralization of a solvent exposed heme propionate and from dehydration of the complex interface. Although direct evidence demonstrating that neutralization of the charge on the heme propionate contributes to the modulation of the redox potential of cytochrome b5 has been obtained, evidence demonstrating that water exclusion from the complex interface plays a similar role has not been conclusive. Herein we report the preparation of the V45I/V61I double mutant of rat liver outer mitochondrial membrane (OM) cytochrome b5. This mutant has been engineered with the aim of restricting water accessibility to the exposed heme edge of cytochrome b5. The X-ray crystal structure of the V45I/V61I mutant revealed that the side chain of Ile at positions 45 and 61 restricts water accessibility to the interior of the heme cavity and protects a large section of the heme edge from the aqueous environment. Electrochemical studies performed with the V45I/V61I mutant of cytochrome b5, and with a derivative in which the heme propionates have been converted into the corresponding dimethyl ester groups, clearly demonstrate that dehydration of the heme edge contributes to the modulation of the reduction potential of cytochrome b5. In fact, these studies showed that exclusion of water from the complex interface exerts an effect (approximately 40 mV shift) that is comparable, if not larger, than the one originating from neutralization of the charge on the solvent exposed heme propionate (approximately 30 mV shift). PMID- 11197481 TI - Surface immobilized biochemical macromolecules studied by scanning Kelvin microprobe. AB - The measurement of work function is a particularly effective method for the characterization of surfaces because of the sensitivity of the parameter to interfacial structure, modification and overall chemistry. Accordingly, techniques for the analysis of work function offer a powerful tool for monitoring surface chemical changes, especially for situations involving the immobilization of new moieties at the interface. In the present paper, we describe the performance of a new, modified scanning Kelvin microprobe which is capable of the tandem measurement of contact potential and surface topography with resolutions of 1 mV and 10 nm, respectively. The lateral resolution is 1 micron. The instrument has been applied to the study of substrates modified by the attachment of biochemical macromolecules such as oligonucleotides and DNA. This preliminary work confirms the great potential of the technique in the study of biocompatibility, macromolecular structure and microarray devices. PMID- 11197482 TI - Polyferredoxin-based electrode materials. AB - Electrochemical oxidation of the hydrosulfide cluster [Fe4S4(SH)4]2- on gold, platinum or vitreous carbon in a methyl cyanide electrolyte leads to the growth of a conducting film. Spectroscopic and other evidence suggests that the film has cubane centres, predominately in the [4Fe4S]3+ oxidation state, which are linked by disulfide ligands to give an anionic array of [Fe4S4(S approximately)4]n- units. X-ray data suggests some long-range order in the electrode material. The polyferredoxin binds redox active cations consistent with an anionic array. PMID- 11197483 TI - Electron-transfer pathways between redox enzymes and electrode surfaces: reagentless biosensors based on thiol-monolayer-bound and polypyrrole-entrapped enzymes. AB - Based on previous results which showed that quinohemo-protein alcohol dehydrogenase (QH-ADH) entrapped within polypyrrole is able to directly transfer electrons via the conducting polymer to the electrode surface, the electron transfer properties of this multi-cofactor enzyme adsorbed and covalently-bound to self-assembled thiol monolayers and bare electrode surfaces has been investigated more closely. While the dissolved enzyme is able to transfer electrons to the electrode via heme c as well as via the more deeply buried PQQ (fast adsorption-chemical reaction-desorption mechanism), an orientation of adsorbed QH-ADH on hydrophobic electrode surfaces, as well as of adsorbed and covalently bound QH-ADH on negatively-charged thiol monolayers could be observed. In these cases the heme c units are pointing towards the electrode surfaces resulting in an optimised direct ET rate. PMID- 11197484 TI - Electrochemical approach to the dynamics of molecular recognition of redox enzyme sites by artificial cosubstrates in solution and in integrated systems. AB - Application of antigen-antibody technology allows the attachment to an electrode surface of an enzyme monolayer structure to which both the enzyme and the mediator are bound. As illustrated with the example of glucose oxidase and a ferrocene mediator, the enzyme preserves its full activity in such structures, which may be easily reproduced. In spite of their fixation to the structure, the mobility of the ferrocene heads is sufficient to ensure that its transport to the enzyme prosthetic group is not rate determining. The reaction is rather controlled by the prior formation of a complex between the ferrocenium ion and the flavin required for electron transfer to occur. The efficiency of this step is affected by steric hindrance and the various observations made with free moving and attached ferrocene-ended poly(ethylene glycol) chains may be rationalized by the interplay of factors controlling their distribution and shape. Analyzing the dynamics of this system, in comparison with previous systems, was thus an occasion to shed further light on the recognition phenomenon. The enzyme monolayer integrated system is a good starting point for the step-by-step construction of spatially ordered multilayered assemblies with strong catalytic efficiencies. Fast responding systems are expected both in terms of electron transport and electron transfer between the mediator and the enzyme. The spatial order resulting from the step-by-step construction should allow a much more precise analysis of electron transport and electron transfer than in conventional assemblies of redox centers. Mastering both the construction and the functioning of such systems should help the design of more complex systems, integrating additional functionalities electrically controlled by means of their electron transport/electron transfer connection to the electrode surface. PMID- 11197485 TI - Direct heterogeneous electron transfer of recombinant horseradish peroxidases on gold. AB - Clean polycrystalline gold electrodes were modified with native glycosylated horseradish peroxidases (HRP) or two different recombinant (carbohydrate free) HRPs; recombinant wild-type HRP (rec-HRP) and recombinant HRP containing a six histidine-tag at the C-terminus of the polypeptide chain (rec-HRP-His), respectively. Only the electrodes modified with the recombinant HRPs exhibited high current responses to H2O2 due to relatively rapid direct electron transfer (ET) between recombinant HRP and gold. The absence of a carbohydrate shell on rec HRP and the additionally existing histidine-tag on rec-HRP-His improved the electrode sensitivity to H2O2 by more than 100 times if compared with the response observed at gold modified with native HRP. Rotating disk electrode experiments indicated that the heterogeneous electron transfer rates are equal to 4.7 and 7.5 s-1 for direct electron transfer between the gold electrode and rec HRP or rec-HRP-His, respectively. PMID- 11197486 TI - Development and comparison of biosensors for in-vivo applications. AB - Electrochemical biosensors have been of increasing interest, especially those developed to be directly applied in diagnostic areas, such as neuroscience. We have been interested in developing a range of biosensors for monitoring glucose, lactate, pyruvate, and glutamate in order to study on-line both brain function in the laboratory and to monitor brain health in neurointensive care. For a biosensor to function effectively in these situations, it has to combine the following characteristics: quick response and high sensitivity, good reproducibility and adequate stability. In this study we compared the performance of a number of different amperometric biosensors strategies. These included ferrocene mediation of immobilised enzymes (system A), a redox hydrogel based system (system B), and a conducting polymer approach using polyaniline (system C). All assays were operated as flow-injection systems with upstream immobilised enzyme beds if necessary. When calibrated for H2O2 systems A and B reacted quickly enough to give quantitative conversion up to 0.2 mM. Above this concentration the response was limited by horseradish peroxidase enzyme kinetics and eventually enzyme loading. System C showed a restricted H2O2 response. When calibrated for glucose (by use of immobilised glucose oxidase) system B exhibited the highest sensitivity but its analytical range was restricted because the system became limited by H2O2 response. System A had low sensitivity for analyte compared to H2O2 and system B, but a greater useful range. Problems of mediator cycling between the immobilised enzymes are discussed. System C gave an excellent linear range but sensitivity was limited by background noise. Stability and reproducibility of the systems are also described. In conclusion, from this study the ferrocene system proved to be overall most useful and has now been used in the first dual on-line monitoring of glucose and lactate in patients in neurointensive care. PMID- 11197487 TI - An independently addressable microbiosensor array: what are the limits of sensing element density? AB - A microdisc sensor array, prepared by thin film technology, has been used as a model for miniaturized multi-functional biosensors. It consists of a series of wells, 20 microns in diameter, possessing a 1000 A Pt layer at the bottom that serves as the indicating electrode. The depth of the wells ranged from 2.3-24 microns, depending on the photoresist employed and the spinning speed used to coat the electrode interconnect grid. Ten such wells were arranged in a circular array within an area of radius 130 microns. The center to center distance between any two of the discs ranged from 30 to 155 microns. Each disc is connected by a conductive film line to corresponding pads on the side of the sensor chip. A cylinder placed on top of the chip array formed the electrochemical cell into which a common reference and counter electrode were placed. The reference electrode was operated at ground potential. Prior to the evaluation of enzyme sensors, an assessment of "chemical cross-talk", the perturbation of sensor response resulting from the overlap of proximal diffusion layers, was made using Fe(CN)6(4-). The preliminary conclusion is that the sensing elements probably must be separated by about 100 microns in order to avoid interference from adjacent sensors. A technique was developed for the precision delivery of enzyme and cross-linking agent to the 2.3 microns cavity, having a capacity of 4 pL. This procedure makes possible the preparation of sensor arrays capable of detecting different analytes by employing different enzymes. The sensors gave reasonably rapid (2-4 s) response with linearity (up to about 10 mM. However, the sensors in the center of the array clearly showed the effects of depletion of substrates by the surrounding sensors. PMID- 11197488 TI - Analysis of individual biochemical events based on artificial synapses using ultramicroelectrodes: cellular oxidative burst. AB - Carbon fiber platinized ultramicroelectrodes placed within micrometres of a single living cell are used to monitor cellular events. This artificial synapse is used here to collect and examine the very nature of the massive oxidative bursts produced by human fibroblasts when their membrane is locally depolarized by a puncture made with a micrometre sized sealed pipette. The electrochemical analysis of the response indicates that oxidative bursts consist of a mixture of a few femtomoles of highly cytotoxic chemicals: hydrogen peroxide, nitrogen monoxide and peroxynitrite, together with nitrite ions, which may result from a partial spontaneous decomposition of peroxynitrite prior to its release by the cell. PMID- 11197489 TI - Protein adsorption on nanoporous TiO2 films: a novel approach to studying photoinduced protein/electrode transfer reactions. AB - We have investigated the use of nanoporous TiO2 films as substrates for protein immobilisation. Such films are of interest due to their high surface area, optical transparency, electrochemical activity and ease of fabrication. These films moreover allow detailed spectroscopic study of protein/electrode electron transfer processes. We find that protein immobilisation on such films may be readily achieved from aqueous solutions at 4 degrees C with a high binding stability and no detectable protein denaturation. The nanoporous structure of the film greatly enhances the active surface area available for protein binding (by a factor of up to 850 for an 8 microns thick film). We demonstrate that the redox state of proteins such as immobilised cytochrome-c (Cyt-c) and haemoglobin (Hb) may be modulated by the application of an electrical bias potential to the TiO2 film, without the addition of electron transfer mediators. The binding of Cyt-c on the TiO2 films is investigated as a function of film thickness, protein concentration, protein surface charge and ionic strength. We demonstrate the potential use of immobilised Hb on such TiO2 films for the detection of dissolved CO in aqueous solutions. We further show that protein/electrode electron transfer may be initiated by UV bandgap excitation of the TiO2 electrode. Both photooxidation and photoreduction of the immobilised proteins can be achieved. By employing pulsed UV laser excitation, the interfacial electron transfer kinetics can be monitored by transient optical spectroscopy, providing a novel probe of protein/electrode electron transfer kinetics. We conclude that nanoporous TiO2 films may be useful both for basic studies of protein/electrode interactions and for the development of novel bioanalytical devices such as biosensors. PMID- 11197490 TI - Layer-by-layer electrostatic deposition of biomolecules on surfaces for molecular recognition, redox mediation and signal generation. AB - Layer-by-layer supramolecular structures composed of alternate layers of negatively charged enzymes and cationic redox polyelectrolyte have been assembled. Glucose oxidase (GOx), lactate oxidase (LOx) and soybean peroxidase (SBP) have been electrically wired to the underlying electrode by means of poly(allylamine) with [Os(bpy)2ClPyCOH]+ covalently attached (PAA-Os) in organized structures with high spatial resolution. Biotinylated glucose oxidase has also been used to assemble step-by-step on antibiotin goat immunoglobulin (IgG) layers and the enzyme was electrically wired by PAA-Os. These spatially organized multilayers with mono- and bienzymatic schemes can work efficiently in molecular recognition, redox mediation and generation of an electrical signal. The concentration of redox mediator integrated into the multilayers, obtained from the voltammetric charge and an estimation of the layer thickness, exceeds by 100-fold the amount of deposited enzyme assessed by quartz crystal microbalance. Differences in GOx electrical wiring efficiency have been detected with the different assembling strategies. The surface concentration of electrically wired enzyme represents a small proportion of all the enzyme molecules present in the multilayers which can be oxidized by the soluble mediator [Os(bpy)2Cl PyCOOH]Cl. This proportion, as well as the rate of FADH2 oxidation by PAA-Os, increases with the number of electrically wired enzyme layers and with the spatial accessibility of the Os moiety to the enzyme active center. PMID- 11197491 TI - Applications of polyion films containing biomolecules to sensing toxicity. AB - This paper describes several applications of polyion-biomolecule films on electrodes related to future development of in vitro chemical toxicity sensors. In the first example, composite films of DNA and ionomers cast onto pyrolytic graphite (PG) electrodes are shown to be useful for detecting DNA damage during incubation with the carcinogen styrene oxide at pH 5.5. Single electrodes can be used to estimate relative damage rates by derivative square wave voltammetry. Films containing the ionomer Nafion gave better reproducibility than another ionomer, Eastman AQ38. In the second example, films containing redox proteins myoglobin (Mb) and cytochrome (cyt) P450cam were constructed in alternate layers with polyions including DNA on rough PG electrodes. Films with reversible protein FeIII/FeII electrochemistry with up to 7 electroactive layers were made. Amounts of electroactive protein on rough PG that were 7 to 17-fold larger than in similar films on smooth gold were achieved because many more layers were electroactive. Films of Mb/DNA also showed oxidation peaks after short incubations with styrene oxide that may be attributable to DNA damage. Results are relevant to the future design of enzyme-DNA films which convert pollutants and drugs to reactive metabolites, followed by electrochemical detection of the resulting DNA damage. PMID- 11197492 TI - The electrochemistry of ubiquinone-10 in a phospholipid model membrane. AB - The electrochemistry of ubiquinone-10, UQ, incorporated over a phospholipid layer adsorbed on a mercury drop electrode has been investigated over a wide pH range. It is shown that the position of the quinone headgroup in relation to the lipid determines the reversibility of the redox chemistry. For pH <7, the reaction follows a disproportionation route involving the ubiquione radical. There is evidence for the presence of a parallel reaction sequence. The bifurcation point appears to occur for the UQ molecule, which disproportionates after protonation and reduction, in parallel with direct electron transfer to yield the UQ--radical anion. The incorporation of UQ in a lipid monolayer makes its reduction very irreversible for pH > 7. PMID- 11197493 TI - Transforming growth factor-beta1 adsorbed to tricalciumphosphate coated implants increases peri-implant bone remodeling. AB - Increasing experimental interest has emerged for the use of growth factors to stimulate bone healing and bone formation in various clinical situations. We and others have demonstrated that recombinant human transforming growth factor-beta1 (rhTGF-beta1) adsorbed onto tricalcium phosphate (TCP)-coated implants can improve mechanical fixation and bone ongrowth. The present study evaluated bone remodeling in newly formed bone and adjacent trabecular bone around TCP-coated implants with and without rhTGF-beta1 adsorption. Unloaded cylindrical grit blasted titanium alloy implants coated with TCP were inserted bilaterally into the femoral condyles of 10 skeletally mature mongrel dogs. The implants were initially surrounded by a 2 mm gap. Implants with 0.3 microg rhTGF-beta1 were compared with implants without growth factor. The dogs were sacrificed after six weeks. Bone remodeling was evaluated by histomorphometry on Goldner-stained undecalcified sections. The bone volume in the gap was increased significantly from 17.6% in the control group to 25.6% in the rhTGF-beta1 group (p = 0.03). Also bone surface was increased in the rhTGF-beta1 group. The osteoclast covered surfaces were increased from 3.6% in the control group to 5.9% in the rhTGF-beta1 group (p = 0.02). In the surrounding trabecular bone no significant changes in bone remodeling parameters was demonstrated. This study suggests that rhTGF-beta1 adsorbed onto TCP-ceramic coated implants accelerates repair activity in the newly formed bone close to the implant, but it does not seem to influence bone remodeling in preexisting bone at a greater distance from the implant. PMID- 11197494 TI - Biocompatibility and biodegradation of intravitreal hyaluronan implants in rabbits. AB - To study the biocompatibility and the biodegradation rate in vivo of new intravitreal implants made with three different hyaluronic acid esters: Hyaff7, Hyaff11 and Hyaff11p75 (100% ethyl ester, 100 and 75% benzyl esters, respectively), the plugs were implanted through a sclerotomy at 3.5 mm from the limbus of rabbit eyes. In order to evaluate the in vivo biodegradation the shaft diameter of the plugs was measured by ultrasound biomicroscopy. Slit lamp microscopy, ophthalmoscopy and ERG were performed periodically. The effects of the implants on ocular tissues were also evaluated histologically. All the plugs showed a good biocompatibilitv. Plugs of both the total esters, Hyaff7 and Hyaff11, were found to undergo a slow dissolution process for 60 and 150 days, respectively. The partial benzyl ester, Hyaff11p75, was completely reabsorbed after 15 days. Analysis of variance showed a high correlation between biodegradation rate and the time of resorption (F = 90.5; p < 0.001). The biodegradation rate of each implant is related to the chemical structure of the three types of Hyaff (F = 4.51; p = 0.005). The present data suggest that intravitreal implants based on hyaluronic acid esters represent useful biocompatible and biodegradable devices for a potential drug delivery system in the treatment of posterior segment ocular diseases. PMID- 11197495 TI - Microphase separation in bioerodible copolymers for drug delivery. AB - This research examines the microstructure of bioerodible polyanhydrides with an eye towards precise design of drug delivery devices. Our main hypothesis is that the bioerodible copolymer poly(1,6-bis-p-carboxyphenoxyhexane-co-sebacic anhydride) (CPH : SA) undergoes micro-phase separation at certain copolymer compositions due to differences in relative hydrophobicity of the co-monomers, resulting in thermodynamic partitioning of drugs incorporated into these copolymers. We investigate the thermal properties, degree of crystallinity, and surface microstructure of several compositions of CPH : SA using differential scanning calorimetry (DSC), wide-angle X-ray diffraction (WAXD), and atomic force microscopy (AFM). We observe that the degree of crystallinity decreases, while the crystal lamellar thickness increases with CPH content. Phase-imaging using AFM indicates the presence of micro-domains in 20 : 80 and 80 : 20 CPH : SA, while poly(SA) and 50 : 50 CPH : SA show no micro-phase separation. Finally, drug polymer interactions are studied by loading the polymers with different amounts of brilliant blue (hydrophilic) and p-nitroaniline (hydrophobic). DSC and WAXD analysis shows that loading hydrophobic drugs into relatively hydrophobic polymers (poly(SA)) lowers melting point that becomes more pronounced with increased drug loading. PMID- 11197496 TI - Synthesis, characterization and in vitro degradation of a new family of alternate poly(ester-anhydrides) based on aliphatic and aromatic diacids. AB - A new family of alternate poly(ester-anhydrides) containing aliphatic and aromatic diacids were synthesized. The dicarboxylic acids were obtained by derivatization of p-hydroxy benzoic acid at the hydroxy terminus with cyclic anhydride (adipic anhydride and succinic anhydride) and subsequently polymerized via the corresponding mixed anhydrides by melt polycondensation. DSC traces revealed that the polymers had low Tg (< 40 degrees C) and no crystallinity. The static contact angle measurements indicated that the poly(ester-anhydrides) were more hydrophobic than poly(D,L-lactide) and poly(adipic anhydride). In vitro degradation of the polymers was also investigated in pH 7.4 PBS at 37 degrees C. It was found that degradation rate of the poly(ester-anhydrides) increased with p carboxy phenyl adipic monoester (CPA) content in the polymers and the degradation duration could be adjusted from ca. 20 days to ca. 2 months. Erosion curve of poly(p-carboxy phenyl adipic monoester anhydride) (PCPA) was characterized by a linear region of weight loss at nearly constant rate in the first 7 days (ca. 80% of weight loss) followed by a gradual decrease region. IR and SEM analysis showed that significant erosion of PCPA occurred in the outer layer and no apparent erosion could be seen in the inner layer of the degrading sample after 7-day degradation. The poly(ester-anhydrides) may be used as either anti-infective polymeric prodrugs or matrices for drug delivery. PMID- 11197497 TI - Behavior of osteoblasts on a type I atelocollagen grafted ozone oxidized poly L lactic acid membrane. AB - With oxidizing poly-L-lactic acid (PLLA) surface by ozone, peroxide groups are easily generated on the surface. Those peroxides are broken down by redox coupling reaction, and provide active species that initiate grafting by reaction with the collagen molecules. The surface density of generated peroxide on a PLLA surface was determined by an iodide method. The maximum concentration of peroxide was about 2.87 x 10(-8) mol/cm2 when ozone oxidation was performed at 60 V for 60 min. After the surface oxidation, type I atelocollagen was grafted onto PLLA surface. All physical measurements on the collagen-grafted surface indicated that the PLLA surface was effectively grafted with type I atelocollagen. Behavior of rat calvaria osteoblasts on type I atelocollagen grafted PLLA (PLLA + COL) surface was observed. Initial attachment of osteoblasts on the surface was significantly enhanced, and it is assumed that the atelocollagen matrix supported the initial attachment and growth of cells. Collagenous protein synthesis of osteoblasts was maintained at relatively low level in the early stage of proliferation due to the primarily existing grafted type I atelocollagen, and then increased in 7 days as the osteoblast differentiated. After 7 days, collagenous protein synthesis in osteoblasts was activated. Alkaline phosphatase (ALPase) activity and mineralization by osteoblasts were promoted on PLLA + COL surface. In comparison with PLLA + COL, non-treated PLLA and tissue culture plate (TCPS) did not show any feature expressed in osteoblasts' maturation up to 9 days in this experiment. The grafted type I atelocollagen provided a favorable matrix for cell migration in relation with collagenase expression. Ozone oxidation might be a favorable method for surface modification of PLLA membranes by collagen grafting, and cell behavior could be modulated by the grafted collagen. PMID- 11197498 TI - Morphology, drug distribution, and in vitro release profiles of biodegradable polymeric microspheres containing protein fabricated by double-emulsion solvent extraction/evaporation method. AB - The surface and internal morphology, drug distribution and release kinetics at 22 degrees C of polyesters such as PCL (polycaprolactone) and PLGA (poly(DL-lactic co-glycolic acid)) 65:35 microspheres containing BSA (bovine serum albumin) have been investigated in order to understand the relationship amongst morphology, drug distribution and in vitro release profiles and to develop controlled release devices for marine fishes in tropical area. CLSM (confocal laser scanning microscope) micrographs reveal that the polyvinylalcohol (PVA as an emulsifier) concentration in the external water phase strongly influences drug distribution within microspheres and release profiles. The presence of PVA in the internal water phase enhances the stabilization of inner water droplets against coalescence. This results in a more uniform drug distribution and a slower BSA release. Different oil-phase volumes and polymer concentrations yield different solvent exchange and precipitation mechanisms, which lead to different morphologies. A low oil-phase volume yields microspheres with a porous matrix and defective skin surface, which gives a high initial BSA burst as well as a fast release profile. Microspheres fabricated from a low polymer concentration have less defective skin surface, but with a less tortuous inner matrix which results in a more rapid BSA release. A higher BSA loading yields a larger concentration gradient between the emulsion droplet and the continuous water phase as well as between the microspheres and the in vitro medium. The former results in a lower encapsulation efficiency, whereas the latter yields a faster initial burst and a more rapid release profile. High stirring speed can reduce microsphere size, but decreases the yield of microspheres. PMID- 11197499 TI - Preparation and performance of protein-adsorption-resistant asymmetric porous membrane composed of polysulfone/phospholipid polymer blend. AB - To obtain protein-adsorption-resistant membrane for hemodialysis, we prepared a polymer blend composed of polysulfone and 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer (PSf/MPC polymer). The content of the MPC polymer in the PSf was 7 and 15 wt%. The asymmetric porous membrane was obtained by the dry/wet membrane processing method. The surface characterization of the PSf/MPC polymer membrane by X-ray photoelectron spectroscopy revealed that the MPC polymer located at the surface. The mechanical strength of the PSf/MPC polymer membrane did not change compared with that of the PSf membrane. On the other hand, the permeability of solute below a molecular weight (Mw) of 2.0 x 10(4) through the PSf membrane increased with the addition of the MPC polymer, which is considered to be an effect of the hydrophilic character of the MPC polymer. The amount of protein adsorbed on the PSf membrane from plasma was reduced by the addition of the MPC polymer. The permeability of low-molecular-weight protein (Mw = 1.2 x 10(4)) did not change even after the PSf/MPC polymer membrane was contacted with plasma protein solution for 4 h, whereas it decreased dramatically in the case of the PSf membrane. Platelet adhesion was also effectively suppressed on the PSf/MPC polymer membrane. Based on these results, the MPC polymer could serve as a doubly functional polymeric additive, that is, to generate a protein-adsorption-resistant characteristic and to render the membrane hydrophilic. PMID- 11197500 TI - In vitro reaction to orthopaedic biomaterials by macrophages and lymphocytes isolated from patients undergoing revision surgery. AB - Periprosthetic tissues observed at sites of loose total joint implants exhibit abundant macrophages, lymphocytes, fibroblasts and particulate debris. Macrophages phagocytose orthopaedic debris and release proinflammatory cytokines, chemokines, matrix metalloproteinases and other substances. In addition, other cell types present in tissues harvested from the bone-implant interface are thought to influence periprosthetic bone resorption. The present study examined the effects of polymethylmethacrylate (PMMA), cobalt chrome molybdenum alloy (CoCr), and titanium-alloy particle challenge on macrophages co-cultured with lymphocytes in vitro. Potential synergistic effects of lymphocytes on macrophage activation were determined by measuring interleukin-6 and tumor necrosis factor alpha release following exposure to orthopaedic biomaterial particles. Exposure of macrophages or macrophages co-cultured with lymphocytes to all three types of particles resulted in increased release of interleukin-6 and tumor necrosis factor-alpha at 48 h, when compared to macrophages or macrophages co-cultured with lymphocytes, respectively, cultured in the absence of particles. Lymphocytes isolated from periprosthetic tissues secreted increased basal levels of cytokines relative to peripheral blood lymphocytes. Higher doses of PMMA and titanium-alloy particles stimulated increased levels of cytokine release in the macrophage and macrophage/lymphocyte groups. In contrast, a higher dose of CoCr particles (0.075% v/v) was not as effective as the 0.015% v/v dose, indicating probable CoCr toxicity. The macrophage/lymphocyte co-culture did not show synergism between the two types of cells with respect to cytokine release. T-cells at the bone-implant interface may alter the biological response to particulate debris. PMID- 11197501 TI - Influence of the degree of acetylation on some biological properties of chitosan films. AB - In this study, we investigated in vitro the role of the degree of acetylation (DA) on some biological properties of chitosan films. We noticed that, whatever the DA, all chitosan films were cytocompatible towards keratinocytes and fibroblasts. We also demonstrated that the higher the DA of chitosan, the lower was the cell adhesion on the films. Fibroblasts appear to adhere twice as much as keratinocytes on these materials. We observed that keratinocyte proliferation increases when the DA of chitosan films decreases. Thus, DA influences the cell growth in the same way as cell adhesion. On the other hand, although they remain alive, fibroblasts do not proliferate on chitosan films. This behaviour is related to an extremely high adhesion on this kind of material, which certainly inhibits cell growth. In conclusion, DA plays a key role in cell adhesion and proliferation, but does not change the cytocompatibility of chitosan. In parallel, it is also important to notice the role played by the surface morphology of the material, a second major parameter which influences the mechanism of adhesion. PMID- 11197502 TI - Corrosion behavior of a welded stainless-steel orthopedic implant. AB - The corrosion behavior of combinations of materials used in an orthopedic implant: the spherical part (forged or forged and annealed) constituting the head, the weld (tungsten inert gas (TIG) or electron beam (EB) techniques), and the cylindrical part (annealed) constituting the shaft of a femoral prosthesis - has been investigated. Open-circuit potentials, potentiodynamic curves, Tafel slope, mixed potential theory and susceptibility to intergranular attack are electrochemical and chemical procedures selected for this work. Electrochemical measurements using a microelectrode have been made in the following zones: spherical part, cylindrical part, weld, and weld/sphere, and weld/shaft interfaces. To detect intergranular attack, the Strauss test has been used. At the interfaces, corrosion currents, measured (Icorr) and predicted (Icouple) are low, in the order of the pico- to nanoampere. The electrochemical behavior of the electron beam (EB) weld is better than that of the tungsten inert gas (TIG). Welds at interfaces can behave either anodically or cathodically. It is better if welds, which are sensitive parts of the femoral prosthesis, behave cathodically. In this way, the risk of starting localized corrosion (pitting, crevice or intergranular corrosion) from a galvanic couple, remains low. From this point of view, the sample with the EB weld offers the best behavior. All the other samples containing a TIG type of weld exhibit a less favorable behavior. The mechanical treatments (forged, and forged and annealed) of the steel sphere did not show any difference in the corrosion behavior. No intergranular corrosion has been observed at the weld/steel interface for unsensitized samples. With sensitized samples, however, a TIG sample has exhibited some localized intergranular corrosion at a distance of 500 microm along the weld/stainless steel (sphere) interface. PMID- 11197503 TI - A novel formulation for controlled release of heparin-DOCA conjugate dispersed as nanoparticles in polyurethane film. AB - Heparin is a potent anticoagulant agent that interacts strongly with antithrombin III to prevent the formation of fibrin clot. In this study, we propose a new method for preparing a heparin-releasing system using a simple solvent casting. The heparin-DOCA conjugate, having an amphiphilic property, was homogeneously mixed with polyurethane in the co-solvent of dioxane, propanol and water. After casting the film, heparin-DOCA was homogeneously dispersed as nanoparticles in a polyurethane film. As the loading amount of heparin-DOCA in the film was increased, nanoparticle size, water uptake, and release rate were increased. Moreover, the percentage of released amount of heparin-DOCA was increased with the increase in the loading amount of heparin-DOCA. This was because the size of heparin-DOCA particles increases with the increase in the loading amount of heparin-DOCA, thereby decreasing the distance between particles and the total diffusion length to the surface. The release rate of heparin-DOCA can be controlled by the amount of the drug being loaded and the film thickness. When the heparin-DOCA loaded on the polyurethane films was above 7.5%, the released heparin-DOCA prevented the formation of fibrin clot and the platelet adhesion on the film surface. PMID- 11197504 TI - Retinal pigment epithelial cell adhesion on novel micropatterned surfaces fabricated from synthetic biodegradable polymers. AB - Novel synthetic biodegradable polymer substrates with specific chemical micropatterns were fabricated from poly(DL-lactic-coglycolic acid) (PLGA) and diblock copolymers of poly(ethylene glycol) and poly(DL-lactic acid) (PEG/PLA). Thin films of PLGA and PEG/PLA supported and inhibited, respectively, retinal pigment epithelial (RPE) cell proliferation, with a corresponding cell density of 352,900 and 850 cells/cm2 after 7 days (from an initial seeding density of 15,000 cells/cm2). A microcontact printing technique was used to define arrays of circular (diameter of 50 microm) PLGA domains surrounded and separated by regions (width of 50 microm) of PEG/PLA. Reversed patterns composed of PEG/PLA circular domains surrounded by PLGA regions were also fabricated. Both micropatterned surfaces were shown to affect initial RPE cell attachment, limit cell spreading, and promote the characteristic cuboidal cell morphology during the 8-h period of the experiments. In contrast, RPE cells on plain PLGA (control films) were elongated and appeared fibroblast-like. The reversed patterns had continuous PLGA regions that allowed cell-cell interactions and thus higher cell adhesion. These results demonstrate the feasibility of fabricating micropatterned synthetic biodegradable polymer surfaces to control RPE cell morphology. PMID- 11197505 TI - We reap only what we sow. PMID- 11197506 TI - A radiation safety infraction notification form. AB - The use of a well constructed form can serve as an official notification of the violation of good radiation safety practice while providing a paper trail for documentation of corrective action. PMID- 11197507 TI - Experience with a medical waste portal monitoring system. AB - A portal monitor was installed to detect radioactivity in trash and laundry leaving the hospital facility. Experiences with selection, installation, calibration and detection capabilities are reviewed. Also reviewed are the topics used in training hospital employees on proper use of the monitor and response detected activity in trash or laundry. PMID- 11197508 TI - Using fault tree analysis to identify causes of non-compliance: enhancing violation outcome data for the purposes of education and prevention. AB - An enhanced coding system for the characterization of notices of violation (NOV's) issued to radiation permit holders in the State of Texas was developed based on a series of fault tree analyses serving to identify a set of common causes. The coding system enhancement was retroactively applied to a representative sample (n = 185) of NOV's issued to specific licensees of radioactive materials in Texas during calendar year 1999. The results obtained were then compared to the currently available summary NOV information for the same year. In addition to identifying the most common NOV's, the enhanced coding system revealed that approximately 70% of the sampled NOV's were issued for non compliance with a specific regulation as opposed to a permit condition. Furthermore, an underlying cause of 94% of the NOV's was the failure on the part of the licensee to execute a specific task. The findings suggest that opportunities exist to improve permit holder compliance through various means, including the creation of summaries which detail specific tasks to be completed, and revising training programs with more focus on the identification and scheduling of permit-related requirements. Broad application of these results is cautioned due to the bias associated with the restricted scope of the project. PMID- 11197509 TI - Minimum detectable activity in gamma-ray spectrometry--statistical properties and limits of applicability. AB - Some statistical properties of the essential physical quantity "Minimum Detectable Activity" were analyzed, as well as the limits of its applicability in gamma-ray spectrometry. It was shown that the Minimum Detectable Activity is not linear with respect to the quantity of the measured sample and it is advisable not to calculate the Minimum Detectable Activity per unit mass or volume (in Bq kg-1 or Bq cm-3). The MDA has a clear decisive relevance to samples that have an identical geometry and chemical composition with that of the sample that was used to derive the MDA. The relative uncertainty of the Minimum Detectable Activity is approximately +/- 32%. It is recommended not to exclude from evaluations those results that are below minimum detectable activities. PMID- 11197510 TI - Measurements in radioactivity should not be recorded as less than MDA. AB - Sometimes the results of measurements in radioactivity are reported as less than MDA. Over the years there have been articles informing the reader that it is incorrect to express the results of measurements as less than MDA. A very brief review of past comments on expressing the results of measurements precedes a discussion of why measurements should not be reported as less than MDA. PMID- 11197511 TI - Some health physics aspects of working with 203Hg in university research. AB - The radioisotope 203Hg is used in university toxicology research experiments. When our commercial vendor ceased the production of the high specific activity 203Hg we required, an alternative source was sought. Other commercial sources were investigated without success leaving the synthesis of this radioisotope to us. This paper outlines the method we used to synthesize 203Hg and provides a summary of our results to date and a discussion of our experiences. PMID- 11197512 TI - Results of a Division of Radiation Protection scrap yard exercise. AB - For years the Division of Radiation Protection (DRP) has participated in exercises, which are required by the Federal Emergency Management Agency (FEMA) to demonstrate our ability to deal with an accident at a nuclear power plant. These demonstrations are defined by objectives and are structured such that they offer little opportunity to practice for real-world radiological events in the exercise. Since real-world radiological incidents do occur throughout the year, this exercise was designed to be as realistic as possible. A scrap yard incident was chosen as the most probable type of event. The exercise was conducted on May 5 and 6, 1999. PMID- 11197514 TI - Review of Electronic Library for Radiation Protection. PMID- 11197513 TI - Ask the expert. PMID- 11197515 TI - Dose rate outside primary barriers. AB - The author has investigated the use of the inverse square function to predict the photon dose rate outside primary barriers for medical accelerators. Measurements of the dose rate as a function of distance outside the barriers were made at five medical accelerator facilities. An analysis of the data showed that the radiation field appears to diverge from a point between the x-ray target and primary barrier. This behavior of the x-ray beam was attributed to scattering of photons in the shield barrier. It was concluded that the dose outside the barrier will be overestimated if the distance from the x-ray target to the point of calculation is utilized to carry out an inverse square correction. PMID- 11197516 TI - Contaminating incident investigation in medicine and biomedical research. AB - Regardless of how well trained, experienced and careful individuals are, if they handle radioactive materials often enough they will eventually have a contaminating incident. When the incident occurs it is imperative that the proper actions are taken to control the incident, minimize contamination and exposure, assure that proper remediation is implemented, assure that the incident remains confined, that no others become contaminated or exposed and that effective remediation is documented. This paper discusses our approach to such incidents and discusses the incident report form and our philosophy of information recording. PMID- 11197517 TI - Statistical methods in epidemiology. VI. Correlation and regression: the same or different? AB - PURPOSE: The statistical terms 'correlation' and 'regression' are frequently mistaken for each other in the scientific literature. Why this is so is unclear. This paper discusses their differences/ similarities arguing that in most circumstances regression is the most appropriate technique to use, since regression incorporates a notion of dependency of one variable on another. METHOD: Pearson's correlation coefficient (r) is introduced as a method for estimating the degree of linear association between two normally distributed variables. The problem of least squares' regression (when y depends on x) is introduced by considering the best-fitting straight line between points on a scatter plot. RESULTS: Correlation, regression analysis and residual estimation are discussed by taking examples from the author's own teaching experiences. CONCLUSIONS: Correlation and regression share some similarities. However, regression is the better technique to use because with it comes a notion of dependency of one variable upon another. Regression model checking includes residual examination. The importance of plotting and examination of residuals cannot be overemphasized. Residual examination should become as much a part of a regression analysis as the estimation of the regression coefficients themselves. PMID- 11197518 TI - The feasibility of a kinematic measure of lip closure during meaningful speech. AB - PURPOSE: Assessment of dysarthria has traditionally been based on perceptual methods. The purpose of this study was to examine the feasibility of using 2D kinematic analysis to measure lip closure during normal speech. METHOD: Retroflective markers (4 mm diameter) were placed on the midline of each lip of three healthy male, caucasian volunteers aged 69 years who repeated the sentence 'My mother made me an apple and blackberry pie' six times. Videorecordings were analysed using the Ariel Performance Analysis System to calculate the distance between the lips before, during and after the sentence. RESULTS: The graphs produced from the data objectively measured the distance between the lips and identified the eight bilabial sounds. However, in spite of stringent study criteria to minimize differences linked to age, gender and race, differences were found between participants. CONCLUSION: Kinematic 2D analysis may have potential for the objective measurement of lip closure in dysarthria in the context of meaningful speech. These results justify further pilot work to explore: the possible variability within defined populations; and the usefulness of 2D kinematic analysis in the measurement of disordered lip closure in dysarthria. PMID- 11197519 TI - Strain and psychological distress among informal supporters of reflex sympathetic dystrophy patients. AB - PURPOSE: A study to investigate strain and psychiatric morbidity in informal caregivers of patients with reflex sympathetic dystrophy (RSD). METHOD: Fifty one caregivers of RSD patients in the community, identified from a support group in Leeds or a conference in Eastbourne completed standardized questionnaire measures of strain, mood, adjustment, positive and negative affectivity and social support. RESULTS: Fifty seven percent of caregivers experienced significant strain and 53% had poor mood. Adjusting for age and gender, partial correlations showed that the experience of strain in caregivers was associated with poor mood, poor psychological adjustment to the patient's illness, high levels of negative affectivity, increased handicap and disability of the patient. CONCLUSIONS: A high proportion of caregivers of RSD patients experience poor mood and significant levels of strain. Caregivers who are poorly adjusted to the illness experience the most strain. These findings suggest a need for intervention to alleviate the negative impacts of caregiving and facilitate adjustment. PMID- 11197520 TI - The modified rivermead mobility index: validity and reliability. AB - PURPOSE: This paper presents the evaluation of the following psychometric properties of the Modified Rivermead Mobility Index (MRMI): face/content validity, responsiveness, test-retest reliability, inter-rater reliability and internal consistency. This mobility scale represents a further development of the Rivermead Mobility Index (RMI). In its new form the scoring was adapted from a two-point to a six-point scale. The number of test items was reduced from fifteen to eight items in order to measure mobility-related items that physiotherapists consider being essential for demonstrating treatment effects in patients following a stroke. METHOD: A consensus exercise with forty-two physiotherapists attending a stroke care conference established face/content validity. Inter-rater and test-retest reliability were examined by assessing thirty patients by two independent raters selected from a pool of eight physiotherapists in two different settings, an elderly care unit and a stroke rehabilitation unit. All patients were hospitalised and had experienced a stroke within the past six weeks. Responsiveness was examined by calculating the effect size statistic on the admission and discharge score of sixteen acute patients following stroke. RESULTS: The results showed that the modified RMI was: responsive to change (effect size = 1.15), stable when tested on two occasions (paired t-test = 0.732; p = 0.47), highly reliable between raters (ICC = 0.98; p < 0.001) with high internal consistency (Cronbach's alpha = 0.93). CONCLUSIONS: These results suggest that when using the Modified RMI to assess patients in the early stages following stroke, similar results can be obtained by different raters, regardless of experience. However there needs to be a difference of more than 4.5 points (degree of measurement error at 95% confidence level) in the overall score to detect true changes in the patient's level of mobility. PMID- 11197521 TI - The actual state of the effects, treatment and incidence of disabling pain in a gender perspective-- a Swedish study. AB - PURPOSE: The purpose of the study was to elicit the actual state of self perceived experience of long-term and/or recurrent pain and its effects as reported by women and men with disabilities due to pain, in order to determine criteria for assessing the need for measures in rehabilitation/occupational therapy. METHODS: The study used a comparative design with a sample randomized from the Swedish population aged 18-58 years (n = 10,000). The inclusion criterion was that the respondents had or had had pain causing activity limitation or restricting participation in daily life. A special questionnaire including items concerning demography, pain, coping, occupations in daily life, work, treatments, care institutions and hospital/care staff visited, was posted to 1,849 persons and was answered by 1,448 respondents (study group n = 1,305, control group n= 117). RESULTS: Gender differences were found in the overall prevalence of pain, women reporting more frequent episodes of pain than men did. Differences were also found in pain variables, in daily occupations, days of sick leave and work variables. Women completed more varied treatment than men. The incidence rate of long-term/recurrent pain in the population studied was 0.07. CONCLUSIONS: As a conclusion from this study, three essential components are suggested for use when assessing the need for rehabilitation/occupational therapy: (1) shoulder/arm or lower back pain of aching, tensed and/or searing character, particularly among women; (2) emotional/affective pain effects causing restlessness and depression, particularly among women; and (3) limitations in daily occupations assessed by FSQ and the demand/control/support model with results falling within the warning zones plus long sick-leave periods. PMID- 11197522 TI - To what extent are the needs of severely disabled people met by community rehabilitation services? A follow-up study. AB - PURPOSE: To evaluate which needs of disabled people would be met over a one year follow-up period and to examine which factors would be predictive of identifying those people who had more needs met from those who had fewer needs met. METHOD: A follow-up study of a cohort of community dwelling disabled people (aged 16-65) from two NHS Health Districts in Southern England with contrasting patterns of rehabilitation provision, who had participated in a cross-sectional interview study one year previously which had assessed their met and unmet needs. The Southampton Needs Assessment Questionnaire was used to examine needs. Disability was evaluated with the OPCS Disability and Severity Scales and perceived health status with the SF-36. RESULTS: Participation rate at follow-up was 92 %. Of the 300 baseline unmet needs reported by 69 of the 77 participants 33% had been met at follow-up. People whose disability had increased more and/or whose mental health status had improved more had greater percentages of their baseline needs met. There was a non-significant trend for smaller percentages of baseline needs to be met in Basingstoke than in Southampton. CONCLUSIONS: At ground level, disabled people's views were taken into account, to some extent, in the provision of rehabilitation services. This input should be made at a higher level, in the overall shaping of services. PMID- 11197523 TI - Why knee disarticulation (through-knee-amputation) is appropriate for non ambulatory patients. AB - PURPOSE: To determine the reason why 79% of knee disarticulation amputees had not received a prosthesis. METHOD: A 10 year survey was carried out of all patients who had undergone a knee disarticulation at our medical centre. RESULTS: Seventeen of the 37 patients that had not received a prosthesis were recognized to be non-ambulators prior to the surgery. Four patients died after the surgery and in 16 of the patients their general condition limited functional ambulation. An effort had been made to ambulate the patients but had failed. CONCLUSIONS: From a biomechanical point of view many advantages are to be gained for sedentary and bedridden amputees when the level of amputation is through-the-knee. PMID- 11197524 TI - An integrated theory of ageing in the nematode Caenorhabditis elegans. AB - Numerous theories of ageing have been proposed, and many have been tested experimentally, particularly using nematode models such as Caenorhabditis elegans. By combining those theories of ageing that remain plausible with recent findings from studies of C. elegans life span mutants, an integrated theory of ageing has been devised. This is formed from 3 interconnected elements: the evolutionary theory of ageing, the oxidative damage theory of ageing, and a nonadaptive programmed ageing theory. This tripartite theory of ageing gives rise to a number of predictions that may be tested experimentally. PMID- 11197525 TI - Appearance of biomarkers of in vitro ageing after successive stimulation of WI-38 fibroblasts with IL-1alpha and TNF-alpha: senescence associated beta galactosidase activity and morphotype transition. AB - Sublethal oxidative stresses increase the proportions of human fibroblasts positive for senescence associated beta-galactosidase activity and accelerate the transition in the fibroblast morphotypes characterising fibroblast ageing. Stimulation of fibroblasts with TNF-alpha or IL-1alpha transiently increases the production of reactive oxygen species (ROS) in human fibroblasts. Here we propose that repeated stimulation of WI-38 fibroblasts with TNF-alpha or IL-1alpha can generate enough ROS to accelerate the transition in the fibroblast morphotypes and increase the proportion of cells positive for senescence associated beta galactosidase activity. The involvement of ROS is suggested by experiments where the stimulation of fibroblasts with TNF-alpha or IL-1alpha are performed in the presence of N-acetylcysteine which increases the intracellular antioxidant potential. It is proposed that the decrease in the proportions of morphotypes I and II, and the increase in the proportions of morphotypes III to VI observed after successive stimulation with TNF-alpha or IL1-alpha is attributed to an increased ROS production occurring during the stimulation. PMID- 11197526 TI - Exercise, oxidative stress and ageing. AB - Skeletal muscle has the unique ability to increase the rate of oxygen usage during contraction. This has led several workers to suggest that by-products of this increased oxygen consumption, oxygen-derived free radicals, may be primarily responsible for exercise-induced damage to skeletal muscle. However, because of this rapidly changing redox state, skeletal muscle has developed a number of different endogenous mechanisms which adapt rapidly following a period of exercise. These include numerous structural and biochemical changes such as increased muscle activity of antioxidant enzymes and content of stress or heat shock proteins (HSPs). This adaptation is associated with protection against the potentially damaging effects of a second period of exercise. In addition, we have recently demonstrated a significant increase in free radical production during a period of nondamaging exercise, which is rapidly followed by a significant increase in the expression of antioxidant enzymes and HSPs, suggesting that a change in redox state of the muscle may act as signal for adaptation. PMID- 11197527 TI - Cytokine/neurotrophin interaction in the aged central nervous system. AB - Age-associated neurodegenerative diseases such as Alzheimer's disease are characterised by neuronal impairment that leads to cognitive deficits. As certain affected neurons depend on trophic factors such as neurotrophins (NTs), impairment in NT function has been suggested to be a component of neuronal damage associated with such disorders. Age-related neurodegenerative diseases are also characterised by high levels of proinflammatory cytokines such as tumour necrosis factor alpha (TNFalpha) in the CNS. Because TNFalpha receptors and certain NT receptors share a high degree of homology and are capable of activating similar signalling pathways, one possibility is that altered cytokine levels may affect NT function in the aged or diseased CNS. Here we wish briefly to review the evidence suggesting a role for cytokine and NT in the onset of age-associated neurodegenerative diseases. We propose that cytokine/NT interactions may alter neuronal homeostasis, thus possibly contributing to some of the neuronal degeneration occurring during such age-associated CNS diseases. PMID- 11197528 TI - Glucocorticoids and the ageing hippocampus. AB - Approximately 30 % of human and mammalian populations develop cognitive impairments with ageing. Many of these impairments have been linked to dysfunction of the hippocampus, a well studied area of the medial-temporal lobe, which is involved in episodic memory and control of the hypothalamo-pituitary adrenal stress axis and, thus, of glucocorticoid secretion. This paper reviews the growing body of studies which explore a possible relationship between lifetime exposure to glucocorticoids and hippocampal impairment. There is now strong evidence which associates hypercortisolemia in aged men with later cognitive dysfunction and this complements a wealth of rodent and other human data. We conclude with a discussion of possible pharmacological and behavioural interventions. PMID- 11197529 TI - Parameters of calcium homeostasis in normal neuronal ageing. AB - The last decade has witnessed a significant turn in our understanding of the mechanisms responsible for the decline of cognitive functions in aged brain. As has been demonstrated by detailed morphological reassessments, the senescence related changes in cognition cannot be attributed to a simple decrease in the number of neurons. It is becoming clearer that a major cause of age-induced deterioration of brain capability involves much subtler changes at the level of synapses. These changes are either morphological, i.e. reduction in the number of effective synapses and/or functional alterations, i.e. changes in the efficacy of remaining synapses. Important questions are now raised regarding the mechanisms which mediate these synaptic changes. Clearly, an important candidate is calcium, the cytotoxic role of which is already firmly established. The wealth of evidence collected so far regarding the changes of Ca2+ homeostasis in aged neurons shows that the overall duration of cytoplasmic Ca2+ signals becomes longer. This is the most consistent result, demonstrated on different preparations and using different techniques. What is not yet clear is the underlying mechanism, as this result could be explained either through an increased Ca2+ influx or because of a deficit in the Ca2+ buffering/clearance systems. It is conceivable that these prolonged Ca2+ signals may exert a local excitotoxic effect, removing preferentially the most active synapses. Uncovering of the role of Ca2+ in the synaptic function of the aged brain presents an exciting challenge for all those involved in the neurobiology of the senescent CNS. PMID- 11197530 TI - Forkhead transcription factors are targets of signalling by the proto-oncogene PKB (C-AKT). AB - Following the discovery that the proto-oncogene protein kinase B (PKB) functions as a downstream element in signalling from phosphoinositide 3'-kinase (PI3 kinase) (Burgering & Coffer, 1995), PKB has been shown to mediate a diverse array of PI3-kinase dependent cellular responses. Most recently PKB-dependent phosphorylation of 3 members of the family of Forkhead transcription factors has been demonstrated to play a role in PI3-kinase dependent effects on transcription. This review focuses on this newly discovered function of PKB in conveying the diversity of PI3-kinase dependent cellular responses. PMID- 11197532 TI - Evolution, stress, and longevity. AB - The disposable soma theory suggests that longevity is determined through the setting of longevity assurance mechanisms so as to provide an optimal compromise between investments in somatic maintenance (including stress resistance) and in reproduction. A corollary is that species with low extrinsic mortality are predicted to invest relatively more effort in maintenance, resulting in slower intrinsic ageing, than species with high extrinsic mortality. We tested this prediction in a comparative study of stress resistance in primary skin fibroblasts and confirmed that cells from long-lived species are indeed more resistant to a variant of stressors. A widely studied example of within-species variation in lifespan is the rodent calorie restriction model. Food-restricted animals show elevations in a range of stress response mechanisms, and it has been suggested that this is an outcome of natural selection for life history plasticity. We have developed a theoretical model for dynamic optimisation of the allocation of effort to maintenance and reproduction in response to fluctuations in food availability. The model supports the suggestion that the response to calorie restriction may be an evolutionary adaptation, raising interesting questions about the hierarchy of genetic control of multiple stress response systems. The model identifies ecological factors likely to support such an adaptation that may be relevant in considering the likely relevance of a similar response to calorie restriction in other species. Comparative and theoretical studies support the role of somatic maintenance and stress response systems in controlling the rate of ageing. PMID- 11197531 TI - The effects of growth hormone and IGF-1 deficiency on cerebrovascular and brain ageing. AB - Research studies clearly indicate that age-related changes in cellular and tissue function are linked to decreases in the anabolic hormones, growth hormone and insulin-like growth factor (IGF)-1. Although there has been extensive research on the effects of these hormones on bone and muscle mass, their effect on cerebrovascular and brain ageing has received little attention. We have also observed that in response to moderate calorie restriction (a treatment that increases mean and maximal lifespan by 30-40%), age-related decreases in growth hormone secretion are ameliorated (despite a decline in plasma levels of IGF-1) suggesting that some of the effects of calorie restriction are mediated by modifying the regulation of the growth hormone/IGF-1 axis. Recently, we have observed that microvascular density on the surface of the brain decreases with age and that these vascular changes are ameliorated by moderate calorie restriction. Analysis of cerebral blood flow paralleled the changes in vasculature in both groups. Administration of growth hormone for 28 d was also found to increase microvascular density in aged animals and further analysis indicated that the cerebral vasculature is an important paracrine source of IGF-1 for the brain. In subsequent studies, administration of GHRH (to increase endogenous release of growth hormone) or direct administration of IGF-I was shown to reverse the age-related decline in spatial working and reference memory. Similarly, antagonism of IGF-1 action in the brains of young animals impaired both learning and reference memory. Investigation of the mechanisms of action of IGF-1 suggested that this hormone regulates age-related alterations in NMDA receptor subtypes (e.g. NMDAR2A and R2B). The beneficial role of growth hormone and IGF-1 in ameliorating vascular and brain ageing are counterbalanced by their well-recognised roles in age-related pathogenesis. Although research in this area is still evolving, our results suggest that decreases in growth hormone and IGF-1 with age have both beneficial and deleterious effects. Furthermore, part of the actions of moderate calorie restriction on tissue function and lifespan may be mediated through alterations in the growth hormone/IGF-1 axis. PMID- 11197533 TI - VEGF enhances intraneural angiogenesis and improves nerve regeneration after axotomy. AB - Whilst there is an increased understanding of the cell biology of nerve regeneration, it remains unclear whether there is a direct interrelationship between vascularisation and efficacy of nerve regeneration within a nerve conduit. To establish this is important as in clinical surgery peripheral nerve conduit grafting has been widely investigated as a possible alternative to the use of nerve autografts. The aim of this study was to assess whether vascular endothelial growth factor (VEGF), a highly specific endothelial cell mitogen, can enhance vascularisation and, indirectly, axonal regeneration within a silicone nerve regeneration chamber. Chambers containing VEGF (500-700 ng/ml) in a laminin based gel (Matrigel) were inserted into 1 cm rat sciatic nerve defects and nerve regeneration examined in relation to angiogenesis between 5 and 180 d. Longitudinal sections were stained with antibodies against endothelial cells (RECA-1), axons (neurofilament) and Schwann cells (S-100) to follow the progression of vascular and neural elements. Computerised image analysis demonstrated that the addition of VEGF significantly increased blood vessel penetration within the chamber from d 5, and by d 10 this correlated with an increase of axonal regeneration and Schwann cell migration. The pattern of increased nerve regeneration due to VEGF administration was maintained up to 180 d, when myelinated axon counts were increased by 78 % compared with plain Matrigel control. Furthermore the dose-response of blood vessel regeneration to VEGF was clearly reflected in the increase of axonal regrowth and Schwann cell proliferation, indicating the close relationship between regenerating nerves and blood vessels within the chamber. Target organ reinnervation was enhanced by VEGF at 180 d as measured through the recovery of gastrocnemius muscle weights and footpad axonal terminal density, the latter showing a significant increase over controls (P < 0.05). The results demonstrate an overall relationship between increased vascularisation and enhanced nerve regeneration within an acellular conduit, and highlight the interdependence of the 2 processes. PMID- 11197534 TI - Ultrastructural characteristics and lectin-binding properties of M cells in the follicle-associated epithelium of chicken caecal tonsils. AB - To clarify the nature of M cells, the detailed ultrastructural characteristics and lectin-binding properties of M cells were investigated in follicle-associated epithelium (FAE) of chicken caecal tonsils. M cells presented various outlines from columnar to dome shaped. Their polymorphism was dependent on the number of harboured intraepithelial migrating cells. The lighter and larger nuclei of M cells were situated at more apical levels in the epithelial lining compared with those of neighbouring microvillous epithelial cells. The microvilli, which were significantly shorter and thicker than those of adjacent microvillous epithelial cells, were sparsely distributed or completely absent on the apical surfaces of M cells. In general, the apical cytoplasm of M cells without microvilli protruded slightly into the intestinal lumen. Numerous small vesicles were often contained in the apical cytoplasm. The numerous small invaginations of the apical and lateral cell surfaces suggested active transportation of luminal substances. No canaliculi existed in the apical cytoplasm of M cells whereas they were often detected in the neighbouring microvillous epithelial cells. A noteworthy finding was the frequent detection of multivesicular bodies in the apical cytoplasm of M cells. These multivesicular bodies suggest some degradation of ingested luminal substances during transcytoplasmic transportation. WGA and 4 other lectins strongly reacted with all epithelial cells except for M cells, this negativity suggesting a means of detecting M cells in chicken caecal tonsils. Three lectins, DSL, ConA and Jacalin, reacted weakly with the glycocalyx on M cells. The positive reactivity might allow chicken M cells to be utilised for specific antigen delivery into the mucosal immune system in some parenteral vaccinations. PMID- 11197536 TI - The mechanical behaviour of a novel mammalian intervertebral joint. AB - The mechanics of mammalian intervertebral joints are complicated by the viscoelastic nature of the connective tissues joining vertebrae, and by multiple vertebral articulations and complex morphologies. Further, interspecific variation in these structures can greatly compound their functional variation between species, making comparative mechanical analyses even more difficult. Despite these sources of variation however, mammalian intervertebral joints universally exhibit a creep relaxation behaviour based on the viscoelastic nature of the soft tissue joint. We have evaluated, in 6 degrees of freedom, the mechanical signature of a novel mammalian lumbar intervertebral joint found in the Scutisorex spine, and compared it with a more typical mammalian joint in the Rattus (rat) lumbar spine. Scutisorex, the hero shrew, is an East African species of shrew with what is likely the most highly modified vertebral morphology in the entire history of mammals. Thus we decided to evaluate the mechanical behaviour of the intervertebral joint of this species, comparing it with a more representative mammal species in Rattus. We built a custom, 6 degrees of freedom, intervertebral joint transducer and a combined axial moment and load application system in order to quantify and compare the complex mechanical behaviour of these joints. Our results suggest that the Scutisorex joint is 5 times more resilient to simple axial torsion per body mass unit than Rattus, and that the complex load (combined axial compression and torsion) mechanical signature of Scutisorex is probably novel among all mammalian intervertebral joints. Under significant but physiological axial compression the Scutisorex intervertebral joint demonstrates no creep relaxation behaviour, simulating the mechanical behaviour of a rigid construct rather than a viscoelastic joint. The purpose of this rigid intervertebral joint in the ecology of Scutisorex remains unknown. PMID- 11197535 TI - Structure of the human tibialis anterior tendon. AB - The structure and vascular pattern of the human tibialis anterior tendon was investigated using injection techniques, light and transmission electron microscopy and immunohistochemistry. From the well vascularised peritenon, blood vessels penetrate the tendon tissue and anastomose with a longitudinally oriented intratendinous network. The distribution of blood vessels within the tibialis anterior tendon was not homogenous. The posterior part of the tendon had a complete vascular network that extends from the musculotendinous junction to the insertion at the first metatarsal and medial cuneiform bones. In the anterior half, the tissue was avascular in a zone with a length of 45-67 mm. This zone was covered by a single layer (approximately 30 microm) of oval shaped cells. Transmission electron microscopy showed that these cells have the characteristics of chondroid cells. This region was stained by Alcian blue at pH 1 which indicates a high concentration of acid glycosaminoglycans and immunohistochemical staining for chondroitin-4-sulphate, chondroitin-6-sulphate and aggrecan was positive. However, immunostaining for the typical cartilage specific type II collagen within this zone was negative. The location of the avascular zone corresponds to the region where the tibialis anterior tendon wraps around the superior and inferior retinacula which serve as fibrous pulleys. This is the region where most spontaneous ruptures of the tibialis anterior tendon occur. The presence of fibrocartilage within gliding tendons is a functional adaptation to compressive and shearing forces. In contrast to reports from the literature about the structure of gliding tendons wrapping around a bony pulley, the gliding zone of the tibialis anterior tendon has only a narrow layer of chondroid cells and proof of type II collagen is lacking. PMID- 11197537 TI - Immunohistochemical analysis of development of desmin-positive hepatic stellate cells in mouse liver. AB - Development of desmin-positive hepatic stellate cells was studied in mice using double immunofluorescent techniques and in vitro cultures with special attention given to their cell lineages. Several studies recently reported on the presence of cells that are immunologically reactive with both antidesmin and anticytokeratin antibodies in young fetal rat livers, and suggested the possibility that these cells give rise to hepatocytes and hepatic stellate cells. At early stages of mouse liver development, stellate cells with desmin-positive filaments were scattered in the liver parenchyma. However, the stellate cells definitely differed from hepatoblasts and hepatocytes in terms of their morphology and expression of desmin and hepatoblast and hepatocyte-specific E cadherin in the liver. Fetal hepatoblasts and hepatocytes did not react with antidesmin antibodies, nor did desmin-positive stellate cells express E-cadherin in vivo and in vitro. Thus it is likely that desmin-positive stellate cells and hepatoblasts belong to different cell lineages. In the fetal liver, the desmin positive stellate cells surrounded blood vessels, and extended their processes to haematopoietic cells and megakaryocytes. Many, but not all, hepatoblasts and hepatocytes were observed to be associated with the stellate cells. At fetal stages, cellular processes positive for desmin in the stellate cells were also thick compared with those in the adult liver, in which desmin-positive stellate cells lay in Disse's space and were closely associated with all hepatocytes. These developmental changes in the geography of desmin-positive cells in the liver parenchyma and their morphology may be associated with their maturation and interactions with other cell types. PMID- 11197538 TI - Influence of age and gender on thoracic vertebral body shape and disc degeneration: an MR investigation of 169 cases. AB - There are limited data detailing the pattern of age and gender-related changes to the thoracic vertebral bodies and intervertebral discs. A retrospective MR investigation, involving T1-weighted midsagittal images from 169 cases, was undertaken to examine age influences on the anterior wedge (anteroposterior height ratio or Ha/Hp), biconcavity (midposterior height ratio or Hm/Hp), and compression indices (posterior height/anteroposterior diameter or Hp/D) of the thoracic vertebral bodies. Disc degenerative changes in the annulus, nucleus, end plate and disc margin were noted on T2-weighted sagittal images for the 169 cases, based on a 3-level grading system. A linear age-related decline in the Ha/Hp and Hm/Hp indices was noted. The Hp/D index increased during the first few decades of life, then decreased gradually thereafter. The prevalence of abnormal findings in the annuli, nuclei and disc margins increased with increasing age, particularly in the mid and lower thoracic discs. Greater disc degenerative changes were observed in males. These findings provide further insight into the nature of thoracic vertebral shape changes across the lifespan, and the typical patterns of degeneration of the thoracic intervertebral discs. PMID- 11197539 TI - Morphological and biochemical re-evaluation of the process of cavitation in the rat knee joint: cellular and cell strata alterations in the interzone. AB - To assess the contribution of apoptosis to the mechanism of synovial joint cavitation, and to clarify morphological cellular changes during cavitation, we investigated the development of the rat knee joint by light and electron microscopy, TUNEL methods, and electrophoresis of DNA fragments. Although cavitation occurred within the interzone, which consists of 2 outer and a middle layer termed the intermediate zone, no morphological or biochemical signs of cell death, in particular apoptosis, were seen in the interzone at any embryonic stage. Microscopic and ultrastructural alterations affecting cell differentiation were clearly observed in the interzone, i.e. mesenchymal cells gradually showed elongation, cytoplasmic vacuolation and pyknosis in the intermediate zone where the elongated cells were arranged in parallel in some strata. Some of these cells were further flattened into spindle cells and the number of strata decreased to 2. The rest of the cells were incorporated secondarily into the outer layers, becoming chondroblasts. Collagen fibrils were arranged in a network structure in the outer layers, which obviously differed from the directional pattern parallel to the long axis of elongated cells in the intermediate zone. In addition, the density of collagen fibrils was higher in the outer layers than in the intermediate zone. During cavitation, the initial separation was detected between the elongated cells in the intermediate zone in paraffin sections at E16.5 and the spindle cells in epoxy sections at E18.5. The spindle cells lining the cavity, namely, the surfaces of the epiphysis and meniscus, finally became chondrocytes. The diminution of proteoglycans and collagen fibrils and the synthesis of hyaluronan in the extracellular matrix are now generally believed to be parts of the mechanism for cavitation based on the concept of 'loss of cohesion'. The microscopic and ultrastructural alterations in the interzone seemed to reflect differences in the arrangement and density of collagen fibrils and the developmental condition of the extracellular matrix between layers. Also it did not seem likely that these alterations inhibit the synthesis of hyaluronan at the presumptive joint line because this synthesis takes place at the plasma membrane. Separation between spindle cells should therefore represent the mechanism for developmentally programmed cavitation. Reorganization of the extracellular matrix is probably necessary for the cellular metamorphoses in the interzone involved in the process of cavitation. PMID- 11197540 TI - Compartments of the adult parasellar region. AB - In the infant the region lateral to the sella turcica which is traditionally termed the 'cavernous sinus' is composed of 3 individual compartments. The aim of this study was to demonstrate a similar compartmentation of the adult cavernous sinus and to identify and quantify the adipose bodies which are located within the compartments. The region of the cavernous sinus in 136 adults was analysed by microdissection and histology. We demonstrate that in 66% of the cavernous sinus in adults is composed of at least 2 compartments and in 22% it is made up of 3. Assimilating the renaming in infants we termed the compartments 'pterygopalatine', 'orbital' and 'lateral sellar'. The pterygopalatine and orbital compartments are connected with extracranial tissue spaces via the superior orbital fissure and contain characteristic adipose bodies. Exact topographic descriptions and measurements of the compartments and their adipose bodies are provided. Our study clearly defines compartmentation of the adult parasellar space in most individuals and thus changes the anatomical view of this space. The direct connection of 2 of these compartments with extracranial tissue spaces and the measurements of their adipose bodies are of interest for surgeons and neuroradiologists. PMID- 11197541 TI - Distribution of cartilage thickness on the head of the human first metatarsal bone. AB - Articular hyaline cartilage takes on the contours of the subchondral bone on which it lies, but its thickness varies between joints, within a single joint and within a single articular surface. Previous studies have correlated articular cartilage thickness distribution with the degree of stress and weight bearing on joint surfaces, but few studies have considered the thickness of the calcified cartilage in relation to these parameters. Here we report a correlation between the cartilage thickness distribution and weight bearing distribution on the head of the 1st metatarsal bone, a component of one of the major weight bearing joints in the lower extremity during the gait cycle. The greatest total and uncalcified articular cartilage thickness was found on the central and lateral distal aspects of the metatarsal head, a region that receives maximal ground reactive force during the propulsive phase of the normal gait cycle. Although the thickness of the calcified cartilage was correlated with the thickness of the uncalcified cartilage, it varied to a lesser extent across the articular surface than did that of the uncalcified cartilage. PMID- 11197542 TI - [Multiple bacterial resistance in daily practice]. AB - Present and future solutions to the problem of bacterial multiple resistance involve physicians, patients and veterinarians. Their behaviour should evolve to take into account the medical and economical issues of antibiotic prescription. The clinical diagnosis requires a more rigorous assessment, based on bacteriological and rapid antigenic tests. Vaccination in both young people and the elderly, is an essential prophylactic tool, which is too often neglected. When a bacterial infection is suspected or proven, priority should be given to a targeted antimicrobial therapy with a bactericidal activity, in order to quickly eradicate pathogens. Therapies should be shorter and questionable antibioprophylaxis should also be avoided. A watch laboratory network should provide physicians with an adequate information on local bacterial resistance patterns on a regular basis, in order to allow them adjusting their prescription. PMID- 11197543 TI - [Prions]. PMID- 11197544 TI - [Gamma irradiation of solid and liquid collagen] . PMID- 11197545 TI - [Methods of obtaining and formation mechanisms of polymer nanoparticles]. AB - Severals processes exist today for manufacturing colloidal systems of nanospheres or nanocapsules. These nanoparticles have applications in various industrial fields such as cosmetic, pharmacy, food industry, agrochemicals.... The formation of nanoparticles allows the protection of an active molecule by a polymeric coating and the release of this product following a perfectly defined profile, which depends on the nature of the polymer, the type of particle and the field of use. The purpose of this article is to expose the different methods of preparation of nanoparticular systems. These methods are classified in two mains categories. The first gathers most of the methods which are based on polymerization reactions, the second presents the use of preformed polymers (of natural or synthetic origin). A thorough study is devoted to the mechanisms of formation, in order to find the advantages and the disadvantages of each technique to support the development of manufactoring processes. PMID- 11197546 TI - Soluble scute proteins of healthy and ill desert tortoises (Gopherus agassizii). AB - OBJECTIVES: To characterize protein composition of shell scute of desert tortoises and to determine whether detectable differences could be used to identify healthy tortoises from tortoises with certain illnesses. ANIMALS: 20 desert tortoises. PROCEDURES: Complete postmortem examinations were performed on all tortoises. Plastron scute proteins were solubilized, scute proteins were separated by use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and proteins were analyzed, using densitometry. Two-dimensional immobilized pH gradient-PAGE (2D IPG-PAGE) and immunoblot analysis, using polyclonal antisera to chicken-feather beta keratin and to alligator-scale beta keratin, were conducted on representative samples. The 14-kd proteins were analyzed for amino acid composition. RESULTS: The SDS-PAGE and densitometry revealed 7 distinct bands, each with a mean relative protein concentration of > 1 %, ranging from 8 to 47 kd, and a major protein component of approximately 14 kd that constituted up to 75% of the scute protein. The 2D IPG-PAGE revealed additional distinct 62- and 68-kd protein bands. On immunoblot analysis, the 14-, 32-, and 45-kd proteins reacted with both antisera. The 14-kd proteins had an amino acid composition similar to that of chicken beta keratins. There was a substantial difference in the percentage of the major 14-kd proteins from scute of ill tortoises with normal appearing shells, compared with 14-kd proteins of healthy tortoises. CONCLUSIONS AND CLINICAL RELEVANCE: The major protein components of shell scute of desert tortoises have amino acid composition and antigenic features of beta keratins. Scute protein composition may be altered in tortoises with certain systemic illnesses. PMID- 11197547 TI - Use of an orally administered combined sugar solution to evaluate intestinal absorption and permeability in cats. AB - OBJECTIVE: To evaluate intestinal permeability and absorption in healthy cats in association with diet and normal intestinal microflora. ANIMALS: 6 healthy domestic shorthair cats. PROCEDURE: A sugar solution containing D-xylose, 30 methyl-D-glucose, L-rhamnose, lactulose, and 51Cr-EDTA was administered intragastrically to healthy cats, and urinary excretion of ingested sugars was determined 5 hours after administration. After the same cats had received metronidazole for 1 month, the study was repeated. A final study was performed while cats were maintained on a new diet differing in composition and processing. RESULTS: Lactulose-to-rhamnose ratios, reflecting intestinal permeability, were higher in cats, compared with values for humans or dogs, and values obtained before and after metronidazole administration (mean +/- SEM; before, 0.40 +/- 0.08; after, 0.45 +/- 0.09) were not significantly different. Intestinal absorption also was unaltered after antibiotic administration, and the xylose-to glucose ratio was 0.70 +/- 0.03 before and 0.71 +/- 0.06 after metronidazole administration. Sugar recovery did not differ significantly while cats were maintained on canned or dry food. CONCLUSIONS AND CLINICAL RELEVANCE: Reference ranges were established for the percentage urinary recovery of orally administered D-xylose, 3-0-methyl-D-glucose, L-rhamnose, lactulose, and 51Cr-EDTA obtained after 5 hours in healthy cats. The intestines of cats appear to be more permeable than those of other species, although the normal bacterial microflora does not appear to influence the integrity or function of the feline intestine, because values obtained for the measured variables before or after antibiotic administration were not significantly different. In addition, differences were not detected when the diet was completely altered. PMID- 11197548 TI - Determination of optimal immobilizing doses of a medetomidine hydrochloride and ketamine hydrochloride combination in captive reindeer. AB - OBJECTIVE: To establish optimal immobilizing doses of medetomidine hydrochloride (MED) with ketamine hydrochloride (KET) for hand- and dart-administered injections in captive reindeer. ANIMALS: 12 healthy 6- to 9-month-old reindeer (Rangifer tarandus tarandus). Procedure An optimal dose was defined as a dose resulting in an induction time of 150 to 210 seconds, measured from the time of IM injection until recumbency. Initially, each stalled reindeer was immobilized by hand-administered injection. If the induction time was > 210 seconds, the dose was doubled for the next immobilization procedure. If it was < 150 seconds, the dose was halved for the next immobilization procedure. This iteration procedure was continued for each reindeer until an optimal dose was found. Later the reindeer was placed in a paddock and darted with its optimal dose as determined by hand-administered injection. Adjusting to a linear relationship between dose and induction time, optimal darting doses for each reindeer were predicted and later verified. RESULTS: The established mean optimal hand- and dart-administered doses were 0.10 mg of MED/kg of body mass with 0.50 mg of KET/kg, and 0.15 mg of MED/kg with 0.75 mg of KET/kg, producing mean induction times of 171 seconds and 215 seconds, respectively. The mean induction time after darting was 5 seconds greater than the upper limit of the predefined time interval. CONCLUSIONS AND CLINICAL RELEVANCE: The higher dose requirement of MED-KET administration outdoors, compared with indoors, was explained by factors inherent in the darting technique and the different confinements. The iteration and the prediction methods seem applicable for determination of optimal doses of MED-KET in reindeer. The iteration and the prediction procedures may be used to reduce the number of experimental animals in dose-response studies in other species. PMID- 11197549 TI - Arrhythmogenic effect of hypercapnia in ducks anesthetized with halothane. AB - OBJECTIVE: To determine effects of hypercapnia on arrhythmias in ducks anesthetized with halothane. ANIMALS: 12 ducks, 6 to 8 months old, weighing 1.1 to 1.6 kg. PROCEDURES: Each duck was anesthetized with a 1.5% mixture of halothane in oxygen, and anesthetic depth was stabilized during a 20-minute period. We added CO2 to the inspired oxygen to produce CO2 partial pressures of 40, 60, and 80 mm Hg in the inspired gas mixture.The CO2 partial pressure was increased in a stepwise manner. When arrhythmias were not evident during inhalation of the gas mixture at a specific CO2 partial pressure, the CO2 partial pressure was maintained for 10 minutes before a sample was collected for blood gas analysis. When arrhythmias were detected, a sample for blood gas analysis was collected after the CO2 partial pressure was maintained for at least 2 minutes, and CO2 inhalation then was terminated. RESULTS: During the stabilization period, PaCO2 (mean +/- SD) was 33 +/- 5 mm Hg,and arrhythmias were not detected. In 6 ducks, arrhythmias such as unifocal and multifocal premature ventricular contractions developed during inhalation of CO2. Mean PaCO2 at which arrhythmias developed was 67 +/- 12 mm Hg. In 5 of 6 ducks with arrhythmias, the arrhythmias disappeared after CO2 inhalation was terminated. CONCLUSION AND CLINICAL RELEVANCE: Analysis of data from this study indicated that hypercapnia can lead to arrhythmias in ducks during halothane-induced anesthesia. Thus, ventilatory support to maintain normocapnia is important for managing ducks anesthetized with halothane. PMID- 11197550 TI - Effect of repetitive bronchoalveolar lavage on cytologic findings in healthy dogs. AB - OBJECTIVE: To determine reference values for cytologic examination results of bronchoalveolar lavage fluid (BALF) and to investigate effects of repeated lavages on pulmonary health and on results of cytologic examination of BALF in dogs. ANIMALS: 16 healthy adult Beagles. PROCEDURE: All dogs underwent pulmonary lavage to obtain BALF. Eleven dogs were repeatedly lavaged 6 times at 5- to 7 week intervals. Analyses for total and differential cell counts and for viability of cells before and after cell processing were performed. Arterial blood gas analysis before and after bronchoalveolar lavage was used to study the safety of the lavage procedure. Histologic and radiologic examinations were used to study effects of repeated lavages on pulmonary health. RESULTS: Mean (+/- SD) cell count was 104 +/- 69 cells/microl, comprising 75 +/- 7% alveolar macrophages, 13 +/- 6% lymphocytes, 5 +/- 4% neutrophils, 4 +/- 5% eosinophils, 2 +/- 2% mast cells, 0.6 +/- 0.7% epithelial cells, and 0.3 +/- 0.4% plasma cells. Centrifugation of samples and washing of cells caused significant cell loss (59 +/- 13%). Repeated lavages did not cause significant variations in cell counts of BALF or results of arterial blood gas analysis, thoracic radiography, or histologic examination of pulmonary specimens. Only a moderate, although significant, decrease in arterial oxygen content was observed after bronchoalveolar lavage. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis indicated that several lavages performed at 5- to 7-week intervals can safely and reliably be used to study the kinetics of pathologic processes in pulmonary tissues or for evaluation of therapeutic efficacy. PMID- 11197551 TI - Polymerase chain reaction analysis for viruses in paraffin-embedded myocardium from dogs with dilated cardiomyopathy or myocarditis. AB - OBJECTIVE: To perform polymerase chain reaction (PCR) analysis on paraffin embedded myocardium from dogs with dilated cardiomyopathy (DCM) and dogs with myocarditis to screen for canine parvovirus, adenovirus types 1 and 2, and herpesvirus. SAMPLE POPULATION: Myocardial specimens from 18 dogs with an antemortem diagnosis of DCM and 9 dogs with a histopathologic diagnosis of myocarditis were evaluated. PROCEDURE: Paraffin-embedded myocardial specimens were screened for viral genome by PCR analysis. Positive-control specimens were developed from cell cultures as well as paraffin-embedded tissue specimens from dogs with clinical and histopathologic diagnoses of viral infection with canine parvovirus, adenovirus types 1 and 2, and herpesvirus. The histologic characteristics of all myocardial specimens were classified regarding extent, location, and type of inflammation and fibrosis. RESULTS: Canine adenovirus type 1 was amplified from 1 specimen from a dog with DCM. Canine parvovirus, adenovirus type 2, and herpesvirus were not amplified from any myocardial specimens. Histologic analysis of specimens from dogs with DCM revealed variable amounts of fibrosis; myocardial inflammation was observed in 1 affected dog. Histopathologic analysis of specimens from dogs with myocarditis disclosed variable degrees of inflammation and fibrosis. CONCLUSIONS AND CLINICAL RELEVANCE: Viral agents canine parvovirus, adenovirus types 1 and 2, and herpesvirus are not commonly associated with DCM or active myocarditis in dogs. Additional studies evaluating for nucleic acid from viruses that less commonly affect dogs or different types of infectious agents may be warranted to gain insight into the cause of DCM and myocarditis in dogs. PMID- 11197552 TI - Effects of Mannheimia haemolytica leukotoxin on apoptosis and oncosis of bovine neutrophils. AB - OBJECTIVE: To investigate the concentration-dependent effects of Mannheimia haemolytica (formerly Pasteurella haemolytica) leukotoxin (LKT) on apoptosis and oncosis in bovine neutrophils and to examine the role of calcium ions (Ca2+) in LKT-induced apoptosis. SAMPLE POPULATION: Neutrophils isolated from blood samples obtained from healthy calves. PROCEDURE: Neutrophil suspensions were exposed to lytic or sublytic dilutions of LKT and then examined by use of transmission electron microscopy (TEM) or gel electrophoresis. Contribution of extracellular Ca2+ to LKT-induced apoptosis was investigated by incubating neutrophils with LKT or control solutions in buffer containing 1 mM CaCl2 or in Ca2+-free buffer containing 1 mM ethylene glycol-bis (b-aminoethyl ether)-N,N-tetraacetic acid (EGTA) prior to diphenyl amine analysis. RESULTS: Examination by TEM revealed that bovine neutrophils exposed to lytic dilutions of LKT had changes consistent with oncosis, whereas neutrophils exposed to sublytic dilutions of LKT and staurosporin, an inducer of apoptosis, had changes consistent with apoptosis. Effects of sublytic dilutions of LKT on apoptosis were confirmed by gel electrophoresis. Replacement of extracellular Ca2+ with EGTA, a Ca2+ chelator, reduced apoptosis attributable to the calcium ionophore A23187, but it did not have significant effects on apoptosis induced by LKT or staurosporin. CONCLUSIONS AND CLINICAL RELEVANCE: The ability of LKT to cause apoptosis instead of oncosis is concentration-dependent, suggesting that both processes of cell death contribute to an ineffective host-defense response, depending on the LKT concentration in pneumonic lesions. Furthermore, although Ca2+ promotes A23187 induced apoptosis, it is apparently not an essential second messenger for LKT induced apoptosis. PMID- 11197553 TI - Effects of the synthetic selectin inhibitor TBC1269 on tissue damage during acute Mannheimia haemolytica-induced pneumonia in neonatal calves. AB - OBJECTIVE: To determine effects of the selectin inhibitor TBC1269 on neutrophil mediated pulmonary damage during acute Mannheimia haemolytica-induced pneumonia in newborn calves. ANIMALS: Eighteen 1- to 3-day-old colostrum-deprived calves. PROCEDURE: Mannheimia haemolytica or saline (0.9% NaCl) solution was inoculated in both cranial lung lobes of 12 and 6 calves, respectively. Calves were euthanatized 2 (saline, n = 3; M haemolytica, n = 4) or 6 hours (saline, n = 3; M haemolytica, n = 8) after inoculation. Four M haemolytica-inoculated calves euthanatized at 6 hours also received TBC1269 (25 mg/kg, IV) 30 minutes before and 2 hours after inoculation. Conjugated diene (CD) concentrations, inducible nitric oxide synthase (iNOS) expression, and apoptotic cell counts were determined in lung specimens collected during necropsy. RESULTS: Conjugated diene concentrations were significantly increased in all M haemolytica-inoculated groups, compared with saline-inoculated groups. Calves treated with TBC1269 had decreased concentrations of CD, compared with untreated calves, although the difference was not significant. Number of apoptotic neutrophils and macrophages increased significantly inTBC1269-treated calves, compared with untreated calves. Inducible nitric oxide synthase was expressed by epithelial cells and leukocytes. However, iNOS was less abundant in airway epithelial cells associated with inflammatory exudates. Degree of iNOS expression was similar between TBC1269 treated and untreated calves. CONCLUSIONS: Mannheimia haemolytica infection in neonatal calves resulted in pulmonary tissue damage and decreased epithelial cell iNOS expression. The selectin inhibitor TCB1269 altered, but did not completely inhibit, neutrophil-mediated pulmonary damage. PMID- 11197554 TI - Evaluation of an in-shoe pressure measurement system in horses. AB - OBJECTIVE: To develop an objective, accurate method for quantifying forelimb ground reaction forces in horses by adapting a human in-shoe pressure measurement system and determine the reliability of the system for shod and unshod horses. ANIMALS: 6 adult Thoroughbreds. PROCEDURE: Horses were instrumented with a human in-shoe pressure measurement system and evaluated at a trot (3 m/s) on a motorized treadmill. Maximum force, stance time, and peak contact area were evaluated for shod and unshod horses. Three trials were performed for shod and unshod horses, and differences in the measured values were examined with a mixed model ANOVA for repeated measures. Sensor accuracy was evaluated by correlating measured variables to clinically observed lameness and by a variance component analysis. RESULTS: 4 of 6 horses were determined to be lame in a forelimb on the basis of clinical examination and measured values from the system. No significant differences were observed between shod and unshod horses for maximum force and stance time. A significant decrease in peak contact area was observed for shod and unshod horses at each successive trial. Maximum force measurements provided the highest correlation for detecting lameness (r = 0.91, shod horses; r = 1.0, unshod horses). A variance component analysis revealed that 3 trials provided a variance of 35.35 kg for maximum force (+/- 5.78% accuracy), 0.007 seconds for stance time (+/- 2.5% accuracy), and 8.58 cm2 for peak contact area (+/- 11.95% accuracy). CONCLUSIONS AND CLINICAL RELEVANCE: The in-shoe pressure measurement system provides an accurate, objective, and effective method to evaluate lameness in horses. PMID- 11197555 TI - Evaluation of a polyvalent enzyme-linked immunosorbent assay incorporating a recombinant p44 antigen for diagnosis of granulocytic ehrlichiosis in dogs and horses. AB - OBJECTIVE: To develop and evaluate a polyvalent ELISA incorporating a highly specific recombinant antigen (p44) for diagnosis of granulocytic ehrlichiosis in dogs and horses. ANIMALS: 32 dogs and 43 horses. PROCEDURE: Results of the ELISA were compared with results of indirect fluorescent antibody (IFA) staining and western immunoblotting incorporating whole-cell antigen. RESULTS: For the canine and equine samples, percentages of samples with positive IFA staining, western immunoblotting, and ELISA results were similar. For 29 (91 %) canine samples and 30 (70%) equine samples, results of IFA staining, western immunoblotting, and the ELISA were in complete agreement. Results of the ELISA for 3 canine serum samples known to contain antibodies to Ehrlichia canis and 12 equine serum samples known to contain antibodies to E risticii were negative. CONCLUSIONS AND CLINICAL RELEVANCE: Results of the present study suggest that a polyvalent ELISA incorporating a recombinant p44 antigen is suitable for detecting antibodies to E equi in dogs and horses. PMID- 11197556 TI - Evaluation of the cardiac actin gene in Doberman Pinschers with dilated cardiomyopathy. AB - OBJECTIVE: To evaluate the coding region of the cardiac actin gene in Doberman Pinschers with dilated cardiomyopathy (DCM) for mutations that could be responsible for the development of the condition ANIMALS: 28 dogs (16 Doberman Pinschers with DCM and 12 mixed-breed control dogs). PROCEDURE: Ten milliliters of blood was collected from each dog for DNA extraction. Polymerase chain reaction (PCR) primers were designed to amplify canine exonic regions, using the sequences of exons 2 to 6 of the cardiac actin gene. Single-stranded conformational polymorphism analysis was performed for each exon with all samples. Autoradiographs were analyzed for banding patterns specific to affected dogs. The DNA sequencing was performed on a selected group of affected and control dogs. RESULTS: Molecular analysis of exons 2 to 6 of the cardiac actin gene did not reveal any differences in base pairs between affected dogs and control dogs selected for DNA evaluation. CONCLUSIONS: Mutations in exons 5 and 6 of the cardiac actin gene that have been reported in humans with familial DCM do not appear to be the cause of familial DCM in Doberman Pinschers. Additionally, evaluation of exons 2 to 6 for causative mutations did not reveal a cause for inherited DCM in these Doberman Pinschers. Although there is evidence that DCM in Doberman Pinschers is an inherited problem, a molecular basis for this condition remains unresolved. Evaluation of other genes coding for cytoskeletal proteins is warranted. PMID- 11197557 TI - Spectral analysis of circadian rhythms in heart rate variability of dogs. AB - OBJECTIVE: To determine characteristics of power spectral analysis of heart rate variability (HRV) during a 24-hour period in dogs and to evaluate the effects of vagal and sympathetic tone on HRV ANIMALS: 16 healthy adult Beagles. PROCEDURE: Power spectral analysis of HRV was conducted, using 24-hour ambulatory ECG recordings. Circadian rhythms were evaluated in terms of absolute units of low frequency (LF) and high-frequency (HF) powers, their ratio (LF:HF), and their adjusted (normalized) units (LF[norm] and HF[norm]). Three or 4 dogs were used for simultaneous measurement of heart rate and respiratory waveform as well as to evaluate treatment (propranolol, atropine, or both) administered to cause blockade of the autonomic nervous system. RESULTS: Values for LF and HF powers, LF:HF, LF(norm), and HF(norm) had obvious rhythmicity in clinically normal dogs. The HF power of HRV in dogs was extremely high, compared with that of other species, and HF peaks corresponded to peaks obtained from respiratory waveforms. Blockade of the autonomic nervous system documented that HRV in dogs was mostly attributable to vagal activity. CONCLUSION AND CLINICAL RELEVANCE: We determined characteristics of power spectral analysis of HRV in dogs, including circadian rhythm of the autonomic nervous system. Power spectral analysis of HRV may provide a useful noninvasive technique for assessing the effect of drugs on activity of the autonomic nervous system in dogs. PMID- 11197558 TI - CRWAD dedicated to Coggins. Conference of Research Workers in Animal Diseases. PMID- 11197559 TI - Use of intraosseous blood for repeated hematologic and biochemical analyses in healthy pigs. AB - OBJECTIVE: To evaluate the clinical and histologic effects of repeated intraosseous (IO) needle placement in domestic pigs and determine whether blood and serum obtained intraosseously could be used for CBC and biochemical analyses. ANIMALS: 5 healthy 10-week-old pigs. PROCEDURE: An IO needle was placed in the proximomedial region of the tibia of anesthetized pigs every other week for 2 months, and IO blood was obtained for CBC and serum biochemical analyses. Results were compared with those obtained for blood collected at the same time from the auricular vein. Two weeks after the final samples were obtained, pigs were euthanatized and tibias were processed for histologic examination. RESULTS: Clinical abnormalities, including lameness, were not detected following IO needle placement. Histologic examination revealed only mild multifocal periosteal fibrosis and slight thickening of the periosteum without evidence of osteomyelitis. Chloride, creatinine, glucose, total protein, sodium, and BUN concentrations, alanine transaminase and gamma glutamyl transpeptidase activities, RBC count, mean corpuscular volume, and Hct did not significantly differ between IO and venous samples. However, aspartate transaminase activity, potassium, hemoglobin, and mean corpuscular hemoglobin concentrations, mean corpuscular hemoglobin, and platelet and WBC counts were significantly different. CONCLUSION AND CLINICAL RELEVANCE: Repeated placement of 10 needles may be a safe and clinically useful method to obtain serial blood samples from domestic pigs, particularly when other vascular sites are not accessible. Intraosseous blood can be used for many of the tests comprising CBC and serum biochemical analyses. PMID- 11197560 TI - Biomechanical properties of braided polyester tapes intended for use as intra articular cranial cruciate ligament prostheses in dogs. AB - OBJECTIVE: To determine the in vitro structural and material properties of braided, multifilament, nonabsorbable polyester tapes, used for intra-articular stabilization of cranial cruciate ligament- (CCL-) deficient stifle joints in dogs, and compare those with properties of multifilament polyamide tapes. SAMPLE POPULATION: 30 polyester tapes (width, 4 mm), 10 polyester tapes (width, 7 mm), and 30 polyamide tapes (width, 4 mm) were tested to failure. Cyclic loading experiments were also performed, using 3 polyester tapes of each width. PROCEDURE: Tapes were mounted in a tensile tester as single loops, simulating intra-operative conditions, and elongated to failure at 1,000 mm/min. Additionally, the behavior of polyester tapes was tested at different elongation rates. In a second series of experiments, biomechanical variables of the polyester tapes were measured after 25 sets of 2,000 cycles between physiologic force limits. RESULTS: Mean (+/- SD) ultimate loads of the 4-mm wide polyamide tapes, 4-mm wide polyester tapes, and 7-mm wide polyester tapes were 266.48 +/- 13.19 301.78 +/- 16.92, and 726.40 +/- 37.74 N, respectively. Corresponding stiffnesses were 15.57 +/- 0.49, 21.63 +/- 2.19, and 34.85 +/- 2.66 N/mm, respectively. Failure properties of polyester tapes were affected by previous cyclic loading. CONCLUSIONS AND CLINICAL RELEVANCE: Polyester tapes of 4- or 7-mm widths should be able to resist forces resulting from weight bearing in dogs, suggesting that these tapes will be effective for stabilization of the stifle joint in dogs with a ruptured CCL. PMID- 11197561 TI - Effects of anti-inflammatory drugs on lipopolysaccharide-challenged and unchallenged equine synovial explants. AB - OBJECTIVE: To evaluate the effects of anti-inflammatory drugs on lipopolysaccharide (LPS)-challenged and -unchallenged equine synovial membrane in terms of production of prostaglandin E2 (PGE2) and hyaluronan, viability, and histomorphologic characteristics. SAMPLE POPULATION: Synovial membranes were collected from the carpal, tarsocrural, and femoropatellar joints of 6 adult horses. PROCEDURE: Synovial membranes from each horse were minced and pooled and explants were treated with one of the following: no drug (control), drug, LPS alone, or LPS and drug. Treatment drugs were phenylbutazone (PBZ), flunixin meglumine (FNX), ketoprofen (KET), carprofen (CRP), meloxicam (MEL), low concentration methylprednisolone (METH), high-concentration METH, dimethyl sulfoxide (DMSO), or an experimental COX-2 inhibitor (dissolved in DMSO). Following 48 hours of culture, medium was assayed for PGE2 and hyaluronan concentration. Synovial explants were assessed for viability and histomorphologic characteristics. RESULTS: For the LPS-challenged explants, PBZ, FNX, KTP CRF MEL, and low-concentration METH suppressed PGE2 production, compared with LPS challenge alone. Only MEL suppressed PGE2 production from LPS-challenged explants, compared with unchallenged explants. Synovial explants maintained > 90% viability and there was no significant difference in viability or hyaluronan production among explants. Histomorphologic scores were significantly decreased for explants treated with low-concentration METH or DMSO. CONCLUSIONS AND CLINICAL RELEVANCE: PBZ, FNX, KTP, CRFP MEL, and low-concentration METH suppressed PGE2 production in LPS-challenged explants. Meloxicam appeared to have more selective suppression of COX-2 activity. Histomorphologic scores suggest detrimental effects of METH, DMSO, and the experimental COX-2 inhibitor. Commonly used nonsteroidal anti-inflammatory drugs suppress induced synovial membrane PGE2 production without detrimental effects on synovial membrane viability and function. PMID- 11197562 TI - Nucleotide and deduced amino acid sequence of equine retinal and pineal gland phosducin. AB - OBJECTIVES: To determine the full-length complementary DNA (cDNA) sequence of equine retinal and pineal gland phosducin (PHD) and to clone these sequences. SAMPLE POPULATION: Samples of equine retinal RNA. PROCEDURE: A primer set was designed for use in identifying a fragment of the equine PHD nucleotide sequence, derived from retinal RNA samples, and subsequently for use to deduce specific primers for additional examination. The full-length cDNA was determined by the method of rapid amplification of cDNA ends (RACE). For full-length cDNA, newly designed primers were used. Nucleotide sequences were analyzed by use of computer software. The deduced amino acid sequence was compared with sequences of PHD reported for other species. In addition, the sequence of equine pineal PHD was cloned. RESULTS: The cDNA nucleotide sequence for equine PHD was 1,209 base pairs (bp) in length with an open-reading frame encoding a protein of 245 amino acids and a calculated molecular mass of 28.214 kd. Similarity with amino acid sequences of PHD from other species was 89 to 93%. Sequences of equine PHD from retina and pineal gland were identical. Equine PHD contained a peptide sequence with 100% homology to an uveitopathogenic peptide reported for rat PHD. CONCLUSIONS: Equine PHD is a highly conserved protein that has homology of immunologic interest with rat PHD. These results establish a basis for studying the role of PHD in ocular inflammation of horses. PMID- 11197563 TI - Use of western immunoblot for evaluation of myocardial dystrophin, alpha sarcoglycan, and beta-dystroglycan in dogs with idiopathic dilated cardiomyopathy. AB - OBJECTIVE: To evaluate the potential importance of dystrophin, alpha-sarcoglycan (adhalin), and beta-dystroglycan, by use of western blot analysis, in several breeds of dogs with dilated cardiomyopathy. SAMPLE POPULATION: Myocardial samples obtained from 12 dogs were evaluated, including tissues from 7 dogs affected with dilated cardiomyopathy, 4 control dogs with no identifiable heart disease (positive control), and 1 dog affected with Duchenne muscular dystrophy (negative control for dystrophin). Of the affected dogs, 4 breeds were represented (Doberman Pinscher, Dalmatian, Bullmastiff, and Irish Wolfhound). PROCEDURE: Western blot analysis was used for evaluation of myocardial samples obtained from dogs with and without dilated cardiomyopathy for the presence of dystrophin and 2 of its associated glycoproteins, alpha-sarcoglycan and beta-dystroglycan. RESULTS: Detectable differences were not identified between dogs with and without myocardial disease in any of the proteins evaluated. CONCLUSIONS AND CLINICAL RELEVANCE: Abnormalities in dystrophin, alpha-sarcoglycan, and beta-dystroglycan proteins were not associated with the development of dilated cardiomyopathy in the dogs evaluated in this study. In humans, the development of molecular biological techniques has allowed for the identification of specific causes of dilated cardiomyopathy that were once considered to be idiopathic. The use of similar techniques in veterinary medicine may aid in the identification of the cause of idiopathic dilated cardiomyopathy in dogs, and may offer new avenues for therapeutic intervention. PMID- 11197564 TI - Prevalence and prognostic importance of hypomagnesemia and hypocalcemia in horses that have colic surgery. AB - OBJECTIVE: To determine the prevalence of hypomagnesemia and hypocalcemia in horses with surgical colic. ANIMALS: 35 horses with surgically managed colic. PROCEDURE: Serum concentrations of total magnesium (tMg2+) and calcium (tCa2+), as well as ionized magnesium (iMg2+) and calcium (iCa2+) were analyzed before surgery and 1, 3, 5, and 7 days following surgery. A lead-II ECG and pertinent clinical data were also obtained at each time. RESULTS: Preoperative serum tMg2+ and iMg2+ concentrations were below the reference range in 6 (17%) and 19 (54%) horses, respectively. Serum concentrations of tCa2+ and iCa2+ were less than the reference range in 20 (57%) and 30 (86%) horses before surgery. Horses with strangulating lesions of the gastrointestinal tract had significantly lower preoperative serum concentrations of iMg2+ and iCa2+, as well as a higher heart rate than horses with nonstrangulating lesions. Horses that developed postoperative ileus had significantly lower serum concentrations of iMg2+ after surgery. Serum concentrations of magnesium and calcium (total and ionized) correlated significantly with the PR, QRS, QT, and corrected QT (QTc) intervals. Horses that were euthanatized at the time of surgery (n = 7) had significantly lower preoperative serum concentrations of iMg2+, compared with horses that survived. Neither serum magnesium nor calcium concentrations were predictors of hospitalization time or survival. CONCLUSIONS AND CLINICAL RELEVANCE: Hypomagnesemia and hypocalcemia were common during the perioperative period, particularly in horses with strangulating intestinal lesions and ileus. Serum concentrations of tMg2+ and tCa2+ were less sensitive than iMg2+ and iCa2+ in detecting horses with hypomagnesemia and hypocalcemia. PMID- 11197565 TI - Evaluation of polymyxin B in an ex vivo model of endotoxemia in horses. AB - OBJECTIVE: To evaluate effects of polymyxin B sulfate (PMB) on response of horses to endotoxin, using an ex vivo model. ANIMALS: 8 healthy horses. PROCEDURE: In a crossover design, 3 doses of PMB (100, 1,000, and 10,000 U/kg of body weight) and physiologic saline solution (control) were evaluated. Prior to and for 24 hours after administration of PMB, blood samples were collected into heparinized tubes for use in 2 assays. For the endotoxin-induced tumor necrosis factor (TNF) assay, blood samples were incubated (37 C for 4 h) with 1 ng of Escherichia coli or Salmonella Typhimurium endotoxin/ml of blood. Plasma was harvested and assayed. For the residual endotoxin activity assay, plasma was collected into sterile endotoxin-free borosilicate tubes, diluted 1:10 with pyrogen-free water, and incubated for 10 minutes at 70 C. Escherichia coli endotoxin (0.1 or 1 ng/ml of plasma) was added to the thawed samples prior to performing the limulus ameobocyte lysate assay. Serum creatinine concentrations were monitored for 1 week. RESULTS: Compared with baseline values, PMB caused a significant dose- and time-dependent decrease in endotoxin-induced TNF activity. Compared with baseline values, residual endotoxin activity was significantly reduced after administration of 10,000 U of PMB/kg. Compared with baseline values, 1,000 and 5,000 U of PMB/kg should inhibit 75% of endotoxin-induced TNF activity for 3 and 12 hours, respectively. Serum creatinine concentrations remained within the reference range. CONCLUSION AND CLINICAL RELEVANCE: Results of the study suggest that PMB is a safe, effective inhibitor of endotoxin-induced inflammation in healthy horses. PMID- 11197566 TI - Pharmacodynamics and pharmacokinetics of ketoprofen enantiomers in sheep. AB - OBJECTIVE: To establish pharmacokinetic and pharmacodynamic properties of a racemic mixture and individual R(-) and S(+) enantiomeric forms of ketoprofen (KTP) in sheep and determine pharmacodynamic variables of KTP by pharmacokinetic pharmacodynamic modeling. ANIMALS: 8 female Dorset crossbred sheep. PROCEDURE: A tissue cage model of inflammation was used. Carrageenan was administered into tissue cages. Time course of cyclooxygenase (COX)-2 inhibition was determined in vivo by measurement of exudate prostaglandin E2 (PGE2) concentrations. Time course of COX-1 inhibition was determined ex vivo by measurement of serum thromboxane B2 (TXB2) concentrations. In addition, plasma concentration-time course and penetration of KTP enantiomers into inflammatory exudate and transudate (noninflamed tissue cage fluid) were investigated. Four treatments were compared: placebo, racemic mixture (rac-KTP [3 mg/kg of body weight, IV]), S(+) KTP (1.5 mg/kg, IV),and R(-) KTP (1.5 mg/kg, IV). RESULTS: Both KTP enantiomers had elimination half-life and mean residence time measurements that were short and volume of the central compartment and steady state volume of distribution that were low. Clearance was rapid, particularly for R(-) KTP Elimination of both enantiomers from exudate was > 10 times slower than from plasma. Both rac-KTP and the individual enantiomers significantly inhibited serum TXB2 concentrations for 12 hours. Rac-KTP and S(+) KTP, but not R(-) KTP, also significantly inhibited PGE2 synthesis in exudate for 12 hours. CONCLUSIONS AND CLINICAL RELEVANCE: Inhibition of serum TXB2 concentration and exudate PGE2 synthesis for similar time courses after S(+) KTP administration indicates that it is a nonselective inhibitor of COX in sheep. PMID- 11197567 TI - Effect of a leukocyte-depleting filter in an extracorporeal circuit used for low flow ischemia and reperfusion of equine jejunum. AB - OBJECTIVE: To determine effect of leukocyte depletion on hematologic, morphologic, and metabolic variables of equine jejunum after induction of arterial low-flow ischemia and reperfusion by use of an extracorporeal circuit. ANIMALS: 14 healthy adult horses. PROCEDURE: A segment of jejunum was surgically removed and maintained in an isolated circuit for 3 hours (control group), arterial flow was reduced to 20% of baseline for 40 minutes followed by 1 hour of reperfusion (low-flow group), or leukocyte depletion was filter-induced, and low flow ischemia and reperfusion were conducted as in the low-flow control group (filter-treated group). Various metabolic, hemodynamic, and histomorphologic variables were evaluated, including effects of electrical field stimulation and L N-nitro-arginine-methyl-ester (L-NAME) on contractile activity. RESULTS: The extracorporeal circuit appeared to maintain the jejunum within physiologic limits for an extended period. Low-flow ischemia with reperfusion induced significant differences in various measurements, compared with control specimens. Significant differences were not detected between the low-flow and filter-treated groups. Myeloperoxidase activity was greater in the low-flow group than the control group, whereas a difference was not detected between control and filter-treated groups. CONCLUSIONS AND CLINICAL RELEVANCE: The extracorporeal circuit maintained intestine for 3 hours in a physiologic state and may be used for simulation of tissue injury. Leukocyte depletion generally did not attenuate the effects of low flow ischemia and reperfusion on equine small intestine. PMID- 11197568 TI - Incidence of the endothelin receptor B mutation that causes lethal white foal syndrome in white-patterned horses. AB - OBJECTIVE: To determine incidence of the Ile118Lys endothelin receptor B (EDNRB) mutation responsible for overo lethal white syndrome (OLWS) and its association with specific types of white patterning. ANIMALS: 945 horses of white-patterned bloodlines and 55 solid-colored horses of other breeds. PROCEDURE: Horses were genotyped by use of allele-specific polymerase chain reaction to determine incidence of the Ile118Lys EDNRB mutation. RESULTS: Genotypes detected were homozygous Ile118, homozygous Lys118, and heterozygous. All foals with OLWS were homozygous for the Ile118Lys EDNRB mutation, and adults that were homozygous were not found. White patterning was strongly associated with EDNRB genotype. Color patterns with highest incidence (> 94%) of heterozygotes were frame overo, highly white calico overo, and frame blend overo. White-patterned bloodlines with lowest incidence of heterozygotes (< 21 %) were tobiano, sabino, minimally white calico overo, splashed white overo, nonframe blend overo, and breeding-stock solid. The mutation was not detected in solid-colored horses from breeds without white patterning. CONCLUSIONS AND CLINICAL RELEVANCE: In homozygotes, the Ile118Lys EDNRB mutation causes OLWS. In heterozygotes, the mutation is usually responsible for a frame overo phenotype. The frame pattern can be combined with other white patterns, making accurate estimation of EDNRB genotype by visual inspection difficult. Wide range of incidence of heterozygotes in various subtypes of white patterned horses indicates different genetic control of these color patterns. Determination of EDNRB genotype by use of a DNA-based test is the only way to determine with certainty whether white-patterned horses can produce a foal affected with OLWS. PMID- 11197569 TI - Head lice resistance: itching that just won't stop. AB - OBJECTIVE: To evaluate the reports of resistance and cross-resistance to pediculicides in the head louse (Pediculus capitis), as well as the mechanisms involved. DATA SOURCES: Literature identified through a MEDLINE search (1966 April 2000) and through other secondary literature databases and/or bibliographies of pertinent articles. DATA SYNTHESIS: Head lice infestation is a common, worldwide problem. The widespread use of insecticide treatments together with inadequate treatment methods has led to a concern regarding the potential development of resistant head lice. This literature review examines the reports of resistance of the head louse as well as the purported mechanisms involved. CONCLUSIONS: Current research suggests that head lice resistance exists, but little is known regarding the actual incidence of this resistance or whether this incidence is increasing. More research is needed to assess the status of this problem. Proposed mechanisms for head lice resistance include knock-down resistance, glutathione S-transferase-based resistance, and monooxygenase-based resistance. PMID- 11197570 TI - NSAID impairment of orthodontic tooth movement. AB - OBJECTIVE: To evaluate the impairment of orthodontic tooth movement caused by nonsteroidal antiinflammatory drugs (NSAIDs). DATA SOURCES: Biomedical literature accessed through MEDLINE (1966-January 2000), EMBASE (1980-January 2000), and International Pharmaceutical Abstracts (1970-January 2000). Key search terms included NSAIDs, orthodontics, and tooth movement. DATA SYNTHESIS: Orthodontic dentistry applies mechanical force to generate tooth movement. Since prostaglandins are mediators of tooth movement, it is reasonable to expect that prostaglandin inhibitors, such as NSAIDs, inhibit or delay tooth movement. An evaluation of studies measuring the extent of NSAID impairment on tooth movement was undertaken. CONCLUSIONS: Results from animal studies have shown that NSAIDs can impair the tooth movement process. Until long-term human data are obtained, acetaminophen remains an appropriate alternative to NSAIDs for treating orthodontic-associated pain. PMID- 11197571 TI - Comparison of Internet and community pharmacies. PMID- 11197572 TI - Colony-stimulating factors in acute leukemia: will we ever have an answer? PMID- 11197573 TI - Pulmonary edema associated with rosiglitazone and troglitazone. PMID- 11197574 TI - Comment: drug-herb interaction. PMID- 11197575 TI - Ritonavir-induced carbamazepine toxicity. PMID- 11197576 TI - Publication rates in Australia, Canada, UK, and US pharmacy schools. PMID- 11197577 TI - Possible interaction between cisapride and digoxin. PMID- 11197578 TI - Aseptic meningitis related to valacyclovir. PMID- 11197579 TI - Evaluation of outcomes in converting from intravenous ondansetron to oral granisetron: an observational study. AB - OBJECTIVE: To describe a systematic evaluation of the outcomes associated with revising institutional guidelines for the prevention of acute chemotherapy induced nausea and vomiting (CINV) to promote cost-effective use of the serotonin (5-HT3) antagonists. METHODS: The 5-HT3 antagonist of choice in the antiemetic guidelines was revised from intravenous ondansetron to oral granisetron in August 1995. Patient assessments were conducted immediately prior to (Period 1) and after (Period 2) guideline revision using validated questionnaires. The effectiveness of the two 5-HT3 antagonists were compared and reported to the prescribing oncologists. Outcomes were assessed one year after guideline revision (Period 3) using identical methods. RESULTS: No difference was found in the rate of total control (no emesis, no nausea) between patients receiving oral granisetron (60%) and intravenous ondansetron (56%) (p = 0.408, Period 1 vs. 2). Nausea severity, the number of emesis episodes, and use of rescue antiemetics were also equivalent. Prescriber compliance with using the 5-HT3 antagonist of choice and dose increased from 48% to 61% following adoption of oral granisetron. By Period 3, compliance increased to 78%, and satisfactory control of acute CINV was again documented. The costs for prevention of acute CINV decreased from $107 in Period 1 (intravenous ondansetron only) to $65 in Period 3 (oral granisetron). CONCLUSIONS: Outcomes associated with use of oral granisetron and intravenous ondansetron were equivalent in this patient population. Guideline revision and outcome documentation by the oncology pharmacists resulted in increased compliance with institution guidelines and a 40% cost savings. PMID- 11197580 TI - Lack of methemoglobinemia with flutamide. AB - OBJECTIVE: To determine whether the nonsteroidal antiandrogenic drug flutamide is a clinically relevant inducer of methemoglobinemia in patients with prostatic cancer. METHODS: Fifty consecutive outpatients with prostatic cancer stage D2 entered the study (age 71.1 +/- 7.3 y). Five patients were lost to follow-up; the remaining 45 patients received the recommended oral dose of flutamide 250 mg three times daily. Total hemoglobin (Hb) and methemoglobin (Met-Hb) concentrations were measured on varying days using an ultraviolet/visible spectrophotometric method with an intra- and interday variability < 8%. In 12 patients, Met-Hb was analyzed before initiating flutamide therapy and after therapy was begun. RESULTS: On average, 2.6 venous blood samples per patient were analyzed with a mean Met-Hb concentration of 1.9% of total Hb. Mean concentrations of > or = 3% were detected in only six patients (13%). The data from 12 patients evaluated before and after initiating flutamide therapy were without significantly different changes. During the study period, no clinical signs of methemoglobinemia were reported or observed. CONCLUSIONS: This study found no clinically relevant increase of Met-Hb concentrations in elderly patients with prostatic cancer during chronic treatment with flutamide. However, clinicians should be aware of the very rare possibility of flutamide-induced methemoglobinemia. PMID- 11197581 TI - Rhabdomyolysis secondary to a drug interaction between simvastatin and clarithromycin. AB - OBJECTIVE: To report a case of rhabdomyolysis resulting from concomitant use of clarithromycin and simvastatin. CASE SUMMARY: A 64-year-old African-American man was admitted to the hospital for worsening renal failure, elevated creatine phosphokinase, diffuse muscle pain, and severe muscle weakness. About three weeks prior to admission, the patient was started on clarithromycin for sinusitis. The patient had been receiving simvastatin for approximately six months. He was treated aggressively with intravenous hydration, sodium bicarbonate, and hemodialysis. A muscle biopsy revealed necrotizing myopathy secondary to a toxin. The patient continued to receive intermittent hemodialysis until his death from infectious complications that occurred three months after admission. There were several factors that could have increased his risk for developing rhabdomyolysis, including chronic renal failure. DISCUSSION: Clarithromycin is a potent inhibitor of CYP3A4, the major enzyme responsible for simvastatin metabolism. The concomitant administration of macrolide antibiotics and other hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have resulted in previous reports of rhabdomyolysis. Other factors may increase the risk of this drug interaction, including the administration of other medications that are associated with myopathy, underlying renal insufficiency, and administration of high doses of HMG-CoA reductase inhibitors. CONCLUSIONS: Macrolide antibiotics inhibit the metabolism of HMG-CoA reductase inhibitors that are metabolized by CYP3A4 (i.e., atorvastatin, cerivastatin, lovastatin, simvastatin). This interaction may result in myopathy and rhabdomyolysis, particularly in patients with renal insufficiency or those who are concurrently taking medications associated with myopathy. PMID- 11197582 TI - Disulfiram-ethanol induced delirium. AB - OBJECTIVE: To report a case of delirium, without major autonomic symptoms, as the primary manifestation of concomitant use of alcohol while taking disulfiram. CASE SUMMARY: A 50-year-old white woman with a history of bipolar disorder, type I, and alcohol dependence being treated with disulfiram was admitted to an inpatient psychiatric unit with a three- to four-day history of a change in mental status, including deficits in orientation, concentration, and visual hallucinations. Significant finding on review of systems included the spurious report of a 9.1-kg weight loss. Tachycardia and nonfocal neurologic signs on physical examination were also noted. Extensive metabolic, infectious, and neurologic work-up revealed no abnormalities that alone could explain the patient's acute confusional state. It was subsequently discovered that the patient had imbibed alcohol on at least two separate occasions while taking disulfiram prior to her change in mental status and that a similar, although shorter, experience had occurred previously. DISCUSSION: This is the first case, to the authors' knowledge, that describes an acute confusional state as the primary manifestation of a patient taking alcohol while being prescribed disulfiram as aversive therapy for alcohol abuse. Possible pathophysiologic mechanisms for delirium as a complication of alcohol ingestion while taking disulfiram include disturbances in various neuroendocrine axes, neurotransmitter systems, and metabolic derangements. Other reports of possible neuropsychiatric complications of disulfiram therapy are also reviewed. CONCLUSIONS: The differential diagnosis for the presentation of delirium in a patient known to be undergoing aversive therapy for alcohol dependence with disulfiram should include nonadherence to alcohol abstinence. PMID- 11197583 TI - Intramuscular ceftriaxone in the treatment of childhood meningitis due to Haemophilus influenzae type F. AB - OBJECTIVE: To describe a case of meningitis caused by Haemophilus influenzae type f (Hif) in a child. CASE SUMMARY: A 2.5-year-old white girl (18 kg) was hospitalized because of acute ataxia. The cerebrospinal fluid culture grew H. influenzae, which was later identified as type f. Therapy was limited by the inability to gain intravenous access. Treatment was initiated with dexamethasone 8 mg (0.44 mg/kg) intramuscularly, one dose on the day prior to initiation of ceftriaxone therapy, and intramuscular ceftriaxone 2 g (111 mg/kg/dose) once a day. After the first day, dexamethasone was administered at 3 mg (0.17 mg/kg/d) orally four times per day for four days. Within two days, the patient became afebrile and improved significantly. The remaining treatments were given during daily hospital visits on an outpatient basis. No complications occurred during the follow-up visits. DISCUSSION: The clinical presentation and therapeutic management of Hif meningitis is similar to that of H. influenzae type b (Hib) meningitis. Factors that may predispose a child to infections caused by Hif include upper respiratory tract infections, day care attendance, Down syndrome, and immunodeficiency. Hif meningitis usually is treated with a third-generation cephalosporin (frequently ceftriaxone). Although most often administered intravenously, intramuscular ceftriaxone can provide a satisfactory clinical outcome in a child with adequate peripheral perfusion but limited intravenous access. The majority of reported cases of Hif meningitis resolve with appropriate antibiotic therapy; however, long-term neurologic sequelae occasionally occur. CONCLUSIONS: Hif occasionally causes pediatric meningitis. In a patient with good perfusion and difficult intravenous access, daily intramuscular administration of ceftriaxone can be an effective treatment option. In this case, Hif meningitis occurred abruptly and resolved within 48 hours of initiation of ceftriaxone and dexamethasone without long-term sequelae. The risks of giving dexamethasone appear to be minimal, although efficacy for preventing Hif complications remains to be proven. PMID- 11197584 TI - Trovafloxacin-associated leukopenia. AB - OBJECTIVE: To report a case of trovafloxacin-associated leukopenia, which occurred in a trauma patient shortly after administration and resolved following discontinuation of the drug. CASE SUMMARY: A 79-year-old white man was admitted to Yale New Haven Hospital after sustaining partial amputation of his right lower leg by an industrial lawn mower. After successful resuscitation, he underwent complete right lower amputation and was treated with intravenous alatrofloxacin mesylate. He developed leukopenia that resolved after discontinuation of the drug. DISCUSSION: Trovafloxacin is a broad-spectrum synthetic fluoroquinolone used for a wide variety of bacterial infections. We report, for the first time in the English-language literature, a case of trovafloxacin-associated leukopenia. The leukopenia resolved promptly after discontinuation of the drug. This association is further supported by the exclusion of other potential causes for this adverse effect. CONCLUSIONS: Leukopenia is a well-recognized adverse effect of several drugs. We report a case of trovafloxacin-associated leukopenia during treatment of a trauma patient. Healthcare personnel should be aware of this possible adverse reaction in patients treated with trovafloxacin. PMID- 11197585 TI - Treatment of bipolar depression with twice-weekly fluoxetine: management of antidepressant-induced mania. AB - OBJECTIVE: To report a case of treatment of bipolar depression and management of antidepressant-induced mania with a low-dose fluoxetine regimen. CASE SUMMARY: A 59-year-old white woman was admitted involuntarily to a New York State psychiatric center with a diagnosis of bipolar (type I) disorder, mixed, with psychotic features. Initial treatment with lithium, olanzapine, and clonazepam produced a remission of manic and psychotic symptoms. However, the patient remained clinically depressed. Addition of oral fluoxetine 10 mg every morning to her medication regimen was followed 22 days later by the development of a manic state. Reduction of the fluoxetine dosage to 10 mg twice weekly was associated with the attainment of euthymia in 18 days. Thirteen days after the fluoxetine dosage reduction, the patient's fluoxetine blood concentration was 20 micrograms/L and the norfluoxetine concentration was reported as 53 micrograms/L. DISCUSSION: To our knowledge, this is the first published case that describes the association between a low-dose fluoxetine regimen and the evolution of a bipolar affective state from depression to euthymia via manic switching. The temporal synchrony of this switching with initial implementation of fluoxetine 10 mg every morning, followed by a dose reduction to 10 mg twice weekly, suggests that bipolar depressed patients are extremely sensitive to low doses of antidepressants and to incremental changes in these doses. However, it also suggests that they can respond clinically to such treatment. Furthermore, our laboratory data indicate that antidepressant blood concentrations may play a contributory role in maintaining the balance between euthymia and mania in these patients. CONCLUSIONS: Manic switching is always a concern when treating a bipolar depressed patient. Utilization of a low-dose antidepressant drug regimen may be a clinically prudent approach in such an individual. PMID- 11197586 TI - Cilostazol: treatment of intermittent claudication. AB - OBJECTIVE: To review the pharmacology and clinical utility of cilostazol, an antiplatelet and vasodilator agent approved for the management of intermittent claudication. DATA SOURCES: Primary literature on cilostazol was identified from a comprehensive MEDLINE literature search (1980-February 2000). Selected meeting abstracts and manufacturer literature were also used as source material. Indexing terms included cilostazol, intermittent claudication, platelet inhibitors, and restenosis. STUDY SELECTION: Human clinical, pharmacokinetic and randomized comparative trials performed in the US and Asia were reviewed. Selected in vitro, ex vivo, and animal studies were evaluated when human data were not available. DATA SYNTHESIS: Intermittent claudication, defined as reproducible discomfort of a muscle group induced by exercise and relieved by rest, is the most common clinical manifestation of peripheral arterial disease (PAD). Cilostazol, a specific inhibitor of cyclic adenosine monophosphate phosphodiesterase in platelets and vascular smooth-muscle cells, is a potent antiplatelet agent and vasodilator that reduces vascular proliferation and has lipid-lowering effects in vivo. Recent multicenter, randomized, placebo-controlled trials have led to approval of cilostazol by the Food and Drug Administration for relief of intermittent claudication in patients with stable PAD. Cilostazol doubled walking distances and improved quality of life compared with placebo in these studies. One trial found that cilostazol was more effective than pentoxifylline, the only alternative pharmacologic therapy for claudication. Although frequent (approximately 50%) minor adverse effects, including headache, diarrhea, and palpitations, may occur in clinical practice, cilostazol has not been associated with major adverse events or increased mortality. Small, nonblind studies suggest that cilostazol may prove useful in preventing thrombosis and restenosis following percutaneous coronary interventions, although these remain unlabeled uses. CONCLUSIONS: The unique combination of antiplatelet, vasodilatory, and antiproliferative effects of cilostazol appear to make it an attractive agent for use in patients with PAD. Clinical trials demonstrating a significant improvement in walking distances with cilostazol therapy suggest that it will be an important tool in improving symptoms and quality of life in patients with intermittent claudication. PMID- 11197587 TI - Neuraminidase inhibitors: zanamivir and oseltamivir. AB - OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of zanamivir and oseltamivir for the prophylaxis and treatment of influenza. DATA SOURCES: A MEDLINE search restricted to English-language journals was conducted (1980-May 2000). STUDY SELECTION AND DATA EXTRACTION: All efficacy and safety trials were included if conducted in humans and published in a journal. Abstracts were included if no other data source was available. DATA SYNTHESIS: Zanamivir and oseltamivir block influenza neuraminidase and prevent the cleavage of sialic acid residues, thus interfering with progeny virus dispersement within the mucosal secretions and reducing viral infectivity. The neuraminidase trials for prophylaxis and treatment of influenza enrolled predominantly young (mean age 29 37 y), healthy, mostly unvaccinated individuals who were at the lowest risk of influenza and its complications. When zanamivir 10 mg inhaled twice daily or oseltamivir 75 mg orally twice daily were used for treatment, systemic symptoms such as myalgias, fever, and headache were reduced by approximately 0.7-1.5 days. Greater efficacy (symptom reduction by 1.5-2.0 d) was noted in proven cases of influenza infection, in febrile patients, and in patients who received the treatment medication within 30 hours of symptom onset. Clinical efficacy did not increase when doses higher than the treatment dose approved by the Food and Drug Administration were used. When given for prophylaxis, zanamivir 10 mg inhaled once daily or oseltamivir 75 mg orally once daily was used for four to six weeks and achieved protective clinical efficacy for laboratory-confirmed influenza ranging from 67% to 74%, depending on whether culture or serologic tests were performed. The most common adverse effects (usually < 5%) included upper respiratory tract symptoms. Patients with asthma or chronic obstructive pulmonary disease who received zanamivir had an increased incidence of a > 20% decline in forced expiratory volume in one second or peak expiratory flow rates. Headaches, nausea, and vomiting were more frequent in the oseltamivir groups than in placebo groups. The most common gastrointestinal adverse effects, nausea and vomiting, were reduced to approximately 10% by administering the medication with food. CONCLUSIONS: Zanamivir and oseltamivir are more effective in preventing culture positive influenza or for treatment of culture-positive influenza in febrile (> or = 37.8 degrees C) individuals. Treatment is more effective if initiated within 30 hours of symptom onset in febrile individuals; however, it is difficult to meet these criteria. More realistically, clinical efficacy is closer to 60-70% and, for treatment started within 48 hours for laboratory-confirmed influenza, symptom reduction is approximately 0.7-1.5 days. If used appropriately to minimize the development of resistance, the neuraminidase inhibitors represent a new and unique class of antiinfluenza agents that can potentially reduce the morbidity associated with influenza. PMID- 11197588 TI - New competition in the realm of renin-angiotensin axis inhibition; the angiotensin II receptor antagonists in congestive heart failure. AB - OBJECTIVE: To critically review the studies comparing angiotensin II (AgII) receptor antagonists with placebo or angiotensin-converting enzyme (ACE) inhibitors in patients with congestive heart failure (CHF). DATA SOURCES: A MEDLINE search (1988 to January 2000) was used to identify pertinent literature. Additional references were also retrieved from selected articles. STUDY SELECTION: As most published CHF studies were performed with candesartan and losartan, these agents are the main focus of this article. However, all identified comparative clinical studies were reviewed and included, regardless of the agent used. DATA SYNTHESIS: AgII receptor antagonists inhibit the effects of AgII at its sub-type 1 receptor, independently of AgII's synthesis pathway. They present a hemodynamic profile similar to that of ACE inhibitors, without reflex neurohormonal activation. They have been shown to be at least as effective as ACE inhibitors in improving symptoms, exercise capacity, and New York Heart Association functional class in CHF patients. Although the ELITE (Evaluation of Losartan in the Elderly) trial suggested that losartan improved survival compared with captopril, this study was not designed to look at mortality. ELITE-II, an adequately powered study, showed no difference in mortality rates between patients taking captopril and those taking losartan. The combination of AgII receptor antagonists and ACE inhibitors provides additional benefit on blood pressure lowering and prevention of ventricular remodeling. AgII receptor antagonists are well tolerated, with an incidence of adverse effects similar to or lower than that of ACE inhibitors. Their lack of effect on bradykinin degradation might explain their lower incidence of cough. CONCLUSIONS: The data cumulated thus far in patients with CHF highlight that ACE inhibitors must remain the treatment of choice and that AgII receptor antagonists may be considered as an acceptable alternative for patients who are intolerant to ACE inhibitors. PMID- 11197589 TI - Opioid antagonists in the treatment of opioid-induced constipation and pruritus. AB - OBJECTIVE: To describe the role of opioid antagonists in the treatment of opioid induced constipation and pruritus. DATA SOURCES: A MEDLINE search was performed (1966-February 2000) for narcotics and opioid antagonists. Results were limited to English-language and clinical trials. Background information was obtained from pharmacology and pharmacotherapy references and review articles. Hand searching of selected bibliographies yielded several references. STUDY SELECTION AND DATA EXTRACTION: Studies were reviewed that examined the use of naloxone, naltrexone, and methylnaltrexone for opioid-related constipation and pruritus. Selected citations included various clinical trials and case series. DATA SYNTHESIS: Opioid agents are used for cancer and nonmalignant pain. Peripheral opioid receptor stimulation due to endogenous (i.e., endorphins) or exogenous (i.e., morphine) stimulants may result in negative adverse effects, including constipation and pruritus. Adjuvant agents, such as laxatives and antihistamines, are often used to treat these adverse effects, but are themselves associated with adverse effects and are sometimes ineffective. Opioid antagonists have demonstrated reversal of peripheral opioid receptor stimulation. Clinical trials show adequate maintenance of pain control, as well as decreases in opioid-induced constipation and pruritus. CONCLUSIONS: Opioid antagonists offer a therapeutic alternative to conventional adjuvant agents, with the risk of loss of analgesia at higher doses. Methylnaltrexone offers the advantage of peripheral action only, therefore not reversing analgesia. Results are promising; however, larger clinical trials are necessary before opioid antagonists become the standard of care for opioid-induced constipation and pruritus. PMID- 11197590 TI - Impact of an intravenous fluconazole restriction policy on patient outcomes. AB - OBJECTIVE: To evaluate both the economic and clinical impact of an intravenous fluconazole restriction policy in a university teaching hospital. METHODS: Intravenous fluconazole was restricted to patients unable to take oral medications due to significant nausea or to patients whose oral intake was restricted. A retrospective chart review and computerized record review was conducted in patients receiving intravenous or oral fluconazole from January 1 to June 30, 1997, and again from January 1 to June 30, 1998, after implementation of the policy. RESULTS: Six-month institutional expenditures for intravenous fluconazole decreased following policy implementation, from $81,900 to $45,400, an estimated annual institutional savings of $73,000. A 47% reduction in the number of patients treated with intravenous fluconazole was observed over the six month period after policy implementation. During this time, the rate of successful clinical outcomes for documented or suspected disseminated Candida albicans infection or febrile neutropenia remained the same (66.6% prepolicy and 65.9% postpolicy; p = 0.95). Similarly, the number of deaths in patients receiving fluconazole remained unchanged (p = 0.31). CONCLUSIONS: A restriction policy for intravenous fluconazole results in significant cost savings, with no significant decrease in successful outcomes or change in mortality. PMID- 11197591 TI - Efficacy of colony-stimulating factors in acute leukemia. AB - OBJECTIVE: To evaluate the literature describing the safety and efficacy of the hematopoietic colony-stimulating factors (CSFs) for the management of treatment related adverse effects in patients with acute leukemia. DATA SOURCES: A systematic MEDLINE search of the English-language literature (1995-April 2000) was performed to identify all randomized trials evaluating CSF use in acute leukemia. The following search terms were used: granulocyte colony-stimulating factor, filgrastim, granulocyte-macrophage colony-stimulating factor, sargramostim, acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), acute nonlymphocytic leukemia, and acute myeloid leukemia. The references from relevant literature were also examined in order to identify reports not discovered in the MEDLINE search. DATA SYNTHESIS: Six randomized trials in pediatric ALL, nine in adult AML, and four in adult ALL have examined the safety and efficacy of the CSFs. Two of the pediatric trials supported a reduction in either the duration of hospitalization or in the incidence of febrile neutropenia when a CSF was employed during the consolidation or intensification phase of chemotherapy. The remaining pediatric trials failed to demonstrate a clinical benefit. In adult AML, eight of the nine trials showed a significant decrease in the time to neutrophil recovery when a CSF was used. Only one of these trials demonstrated a decrease in hospital stay and none showed a decreased incidence of infection for patients who received a CSF. Three of the four trials in adult ALL demonstrated the efficacy of a CSF in decreasing the number of days to neutrophil recovery. Only one trial demonstrated that a CSF led to a reduction in the number of hospital days. Trials in children or adults have not demonstrated that the CSFs influence the long-term outcome of patients with acute leukemia. CONCLUSIONS: The published studies document a decrease in the time to recovery from neutropenia when patients with acute leukemia are treated with a CSF. However, a consistent reduction in infectious complications or in the duration of hospitalization has not been demonstrated when a CSF is used for either pediatric or adult patients. Very limited data exist to support the premise that CSFs meet the criteria established by the American Society of Clinical Oncology for demonstrating the value of these agents. Further careful study focused on resource utilization and pharmacoeconomics may help to elucidate how healthcare institutions may most effectively employ CSFs to treat patients with acute leukemia. PMID- 11197592 TI - Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors in the brain. AB - Recent progress in research on pituitary adenylate-activating polypeptide (PACAP) with a special emphasis on the brain is reviewed. PACAP is a pleiotropic neuropeptide that belongs to the secretin/glucagon/vasoactive intestinal peptide family. PACAP functions as a hypothalamic hormone, neurotransmitter, neuromodulator, and neurotrophic factor. Studies on the gene encoding the PACAP precursor and the specific PACAP receptor (PAC1-R) and its subtypes have provided information on the control of gene expression for PACAP, and the relationship between the receptor subtypes and the signal transduction pathways. The PAC1-R is a G protein-coupled receptor with seven transmembrane domains and belongs to the VIP receptor family. At least eight subtypes of PAC1-R result from alternate splicing. Each subtype is coupled to specific signaling pathways, and its expression is tissue or cell specific. PACAP stimulates the release of arginine vasopressin and increases cytosolic Ca2+ ([Ca2+]i). PACAP serves as a neurotransmitter and/or neuromodulator and the activation of the PAC1-R stimulates a cAMP-protein kinase A signal transduction pathway which in turn evokes the [Ca2+]i signaling system. More importantly, PACAP is a neurotrophic factor that may play an important role during the development of the brain. The PAC1-R is actively expressed in different neuroepithelia from early developmental stages and expressed in various brain regions during prenatal and postnatal development. In the adult brain, PACAP appears to function as a neuroprotective factor that attenuates the neuronal damage resulting from various insults. PMID- 11197593 TI - Morphology of the metopic suture during the fetal period. AB - Assessment of the position and size of the metopic suture and anterior fontanelle is important in the routine examination during fetal period and in newborn infants. The aim of this study is to clarify the average size and its developmental changes of the anterior fontanelle and metopic suture by morphometry. Fifty-one cases were examined over a developmental period ranging from fetus of 14 weeks gestation to full term neonate. The width, and length of heads as well as head circumference of all fetuses were measured. The metopic suture and anterior fontanelle sizes were determined. The nearest distances between the parietal bones to the opposite frontal bones, and the distances between the nasion and lower angle of the anterior fontanelle, bregma and upper angle of the anterior fontanelle were measured. The averages of longitudinal and transverse diameters and areas of anterior fontanelle were calculated. Significant correlation was found between all the parameters and gestational ages, and between the sizes of the metopic suture and of skulls. There was no difference between male and female in any of the parameters. In our study, closed metopic suture was not observed. The anterior fontanelle is easy to palpate, and its enlargement might occasionally be helpful in the clinical examination of the newborn infants. The presence of a wide metopic suture may indicate the possibility of additional defects and anomaly in the newborn. PMID- 11197594 TI - Hepatic grooves and portal segmentation. AB - The aim of the present study was to examine the topographical relationship between the locations of the grooves and the borders of Couinaud's portal segments. We found 79 grooves on the diaphragmatic surfaces of 50 livers from 420 cadavers. Most grooves were located within segment VIII wholly (31/79) or partially (39/79). By contrast, only 11 grooves corresponded to the border between two segments (segments VIII/IV in 6 cases and segments VIII/VII in 5 cases). Diaphragmatic indentations (fold-like protrusions) into the groove were observed in 1 case. Our results suggest that the grooves did not form during the early embryonic period when intrahepatic vessels and ducts ramify, but that they formed during a later stage of diaphragmatic growth after establishment of the basic segmental configuration of the liver. The grooves do not seem to be critical landmarks for segmental borders of the liver. PMID- 11197595 TI - [Three-dimensional architecture of the intrinsic tongue muscles using a modified alkaline maceration method]. AB - The three-dimensional architecture of the intrinsic tongue muscle fibers using the anterior part of the rabbit tongue was studied by scanning electron microscopy with a modified chemical-maceration method. The tongue tissues fixed with 10% formalin solution were treated with 1% OsO4 solution at 5 minutes for hardening of the specimen surface. Subsequently, they were immersed in 6N-NaOH solution for 30 minutes at 60 degrees C for the removal of connective tissues followed by dissection of muscle fibers under a binocular microscope to clarify the structure of the intrinsic tongue muscles. The specimens were treated with tannic acid and OsO4 (conductive staining method; Murakami, 1974), and observed with a SEM. Muscular fiber bundles of the transverse and vertical muscles of the tongue changed their direction at the alignment on the sites where the bundles enter the longitudinal muscles from the innermost surface to form monolayers of muscular bundles extending anteroposteriorly. These muscular bundles formed tunnel-like structures each of which covered a longitudinal muscle bundle. It was considered that these tunnel-like structures support the contraction of the longitudinal muscles as the "muscular sheath". PMID- 11197596 TI - Immune balance in critically ill patients. AB - The systemic inflammatory response reflects the non-specific clinical expression of a profound activation of the body's immune responsive elements. Immune activation and immune suppression coexist in the blood of patients with severe sepsis. It is their interaction and the resultant host parenchymal responses that ultimately define the course of sepsis. Importantly, neither profound immune activation (pro-inflammatory) or immune suppression (anti-inflammatory) characterize the dominant process. Rather, there is a combined low grade pro inflammatory state associated with an immune hyporesponsiveness that defines the usual immunologic state of the patient with severe sepsis. PMID- 11197597 TI - T cell integrin activation by chemokines in inflammation. AB - The adhesive function of integrins is regulated through cytoplasmic signaling induced by several stimuli, whose process is designated as "inside-out signaling". A large number of lymphocytes are recruited to the sites of inflammation where they form an essential component of the response to infection, injury, autoimmune disorders, allergy, tumor invasion, atherosclerosis and so on. The recruitment of leukocytes into tissue is regulated by a sequences of interactions between the circulating leukocytes and the endothelial cells. Leukocyte integrins play a pivotal role in leukocyte adhesion to endothelial cells. During the process, the activation of integrins by chemokines is essential for integrin-mediated adhesion in which a signal transduced to the leukocyte converts the functionally inactive integrin to an active adhesive configuration. The present review documents the relevance of cytoplasmic signaling and cytoskeletal assembly to integrin-mediated adhesion induced by chemokines during inflammatory processes. PMID- 11197598 TI - T cell chemokine receptor expression in human Th1- and Th2-associated diseases. AB - The interaction between chemokines and their receptors is an important step in the control of leukocyte migration into sites of inflammation. Chemokines also mediate a variety of effects independent of chemotaxis, including induction and enhancement of Th1- and Th2-associated cytokine responses. Recent studies have shown that human Th1 and Th2 clones, activated under polarizing conditions with polyclonal stimuli in vitro, display distinct patterns of chemokine receptor expression: Th1 clones preferentially express CCR5 and CXCR3, while many Th2 clones express CCR4, CCR8 and, to a lesser extent, CCR3. These differential patterns of chemokine receptor expression suggest a mechanism for selective induction of migration and activation of Th1- and Th2-type cells during inflammation and, perhaps, normal immune homoeostasis. Studies have begun to examine T cell chemokine receptor expression in vivo to determine the relevance of these in vitro observations to human Th1- and Th2-associated diseases. In this review, we critically examine recent reports of T cell chemokine receptor expression in human autoimmune disorders (multiple sclerosis and rheumatoid arthritis) and atopic disorders (allergic rhinitis and asthma) which are believed to arise from inappropriate Th1- and Th2-dominated responses, respectively. PMID- 11197599 TI - Interleukin 15: its role in inflammation and immunity. AB - Interleukin 15 (IL-15) is a 14-15 kDa polypeptide that belongs to the 4 alpha helix-bundle family of cytokines and was originally discovered due to its T cell proliferative activity. It utilizes the signal-transducing beta/gamma polypeptides of the IL-2 receptor complex, thus sharing many biological activities with IL-2, in addition to its high-affinity private receptor subunit IL-15R alpha. Accumulating evidence indicates that the biological relevance of IL 15 may not solely be confined to T lymphocytes, but to a variety of cell populations within the immune system as well as outside the immune system of the host. The expression of both IL-15 and its high-affinity receptor component, IL 15R alpha, are readily demonstrable in a wide variety of tissues and appear to be augmented in response to environmental/stress stimuli and infectious agents. There is increasing evidence to suggest that IL-15 may play an important role in protective immune responses, allograft rejection and the pathogenesis of autoimmune diseases, where mononuclear cell infiltration is a hallmark feature. Herein, the effects of IL-15 on cells associated with host defense, immunity and inflammation are reviewed and support a central role for this cytokine in orchestrating multiple aspects of effector functions in immunity and inflammation. PMID- 11197600 TI - Cytokines and costimulatory molecules: positive and negative regulation of the immune response to Cryptococcus neoformans. AB - Cytokines are small proteins or glycoproteins that transmit information from one cell to another. Most cells in the body secrete and respond to cytokines and their effects have been described on a myriad of cellular functions. Cytokine interactions may not be linear, thus making the system extremely intricate and with unpredictable features. Therefore, each model of disease may be unique, with its own mechanism of autoregulation dictated by positive and negative feedback involving cytokines and costimulatory molecules. The emergence of some cytokines over others in the course of Cryptococcus neoformans infection may characterize a positive or negative outcome of cryptococcosis. Much less is known about the influence of costimulatory molecules in regulating C. neoformans immune response. The available information indicates a critical role for proinflammatory cytokines such as tumor necrosis factor alpha and interleukin 12 (IL-12). The positive role of interferon gamma in infected tissue as an inducer of antimicrobial function of innate immune cells and as positive feedback for IL-12 induction appears to be indisputable. In vitro studies indicate that costimulatory molecule expression appears to be regulated on antigen-presenting cells by C. neoformans and increased expression of B7-1 and CD40 on these cells may promote a protective response. These studies await confirmation in an in vivo system. The interplay between cytokines and costimulatory molecules has been scarcely explored and additional details are needed to better understand how they convey positive and negative information to immune cells in response to C. neoformans. PMID- 11197601 TI - Prostaglandins and inflammation: the cyclooxygenase controversy. AB - Prostaglandins (PGs) are arachidonic acid metabolites produced by the action of the enzyme cyclooxygenase (COX). Although PGs are important mediators of inflammation in various diseases, they also are key factors in the physiological regulation of gastrointestinal and renal homeostasis. The finding that two distinct COX isoforms are responsible for PG synthesis has provided basis to the opposite actions of PGs in inflammation and homeostasis regulation. COX-1-derived PGs are thought to mediate cytoprotective actions on the gastrointestinal mucosa, whereas COX-2-derived PGs are assumed to display pro-inflammatory properties. This dichotomy has led to the development of selective inhibitors of COX-2 activity which are safer for the gastrointestinal mucosa than the classic inhibitors of both COX isoforms. However, some COX-2 anti-inflammatory properties have been recently demonstrated in several experimental models of inflammation. These studies have raised some concern about the potential adverse effects of COX 2 selective inhibitors. In addition, there is evidence that COX-1 displays pro inflammatory properties, depending on the organ and on the stage of the inflammatory response. This review will focus on the roles of COX-1 and COX-2 in inflammation, based on studies involving pharmacologic COX inhibitors as well as COX knock-out mice, with a particular emphasis on the gastrointestinal tract. PMID- 11197602 TI - Nuclear import of arachidonate 5-lipoxygenase. AB - Leukotrienes are lipid messenger molecules that are secreted by leukocytes to orchestrate a rapid and prolonged immune response. The enzyme 5-lipoxygenase catalyzes the rate-limiting first two steps in the synthesis of leukotrienes from arachidonic acid. Although it has long been known that 5-lipoxygenase moves from the cytoplasm to a membrane following activation, it has only recently been recognized that the enzyme may shuttle into and out of the nucleus before activation. The regulation of this movement of soluble 5-lipoxygenase between the cytoplasm and the nucleoplasm, as well as its impact on 5-lipoxygenase action, leukotriene synthesis and cell function, is only now being elucidated. This review details the state of our understanding of the nuclear import of 5 lipoxygenase and its potential importance in immunity. PMID- 11197603 TI - Suppression of mast cell activation by glucocorticoid. AB - Mast cells play a critical role in allergic diseases. When mast cells are activated by cross-linking of their high affinity IgE receptors by the antigen and IgE antibodies, release of chemical mediators is followed by secretion of multiple cytokines. We report that IL-3-dependent mucosal-type mast cells undergo apoptosis when IL-3 is withdrawn. In addition, cross-linking of high affinity IgE receptors prevents apoptosis of mast cells by paracrine mechanisms, producing IL 3, IL-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF). However, the secretion of endogenous growth factors are not enough for cell survival, whereas IL-4 induces cell aggregation by expressing adhesion molecules such as leukocyte function-associated antigen 1 (LFA-1), and makes it reactive to endogenous growth factors by contact cell to cell interaction. On the other hand, dexamethazone down-regulates the expression of intracelluar adhesion molecule 1 (ICAM-1) and IL-4 in activated mast cells, by which the self-aggregation of mast cells is inhibited and apoptosis is induced. Thus, glucocorticoids suppress mast cell survival by inhibiting IL-4 production and expression of adhesion molecules. PMID- 11197604 TI - Pathogenetic mechanisms of atopic dermatitis. AB - Atopic dermatitis (AD) is a chronic inflammatory disease which results from complex interactions between genetic and environmental mechanisms. An altered lipid composition of the stratum corneum is responsible for the xerotic aspect of the skin and determines a higher permeability to allergens and irritants. Keratinocytes of AD patients exhibit a propensity to an exaggerated production of cytokines and chemokines, a phenomenon that can have a major role in promoting and maintaining inflammation. Specific immune responses against a variety of environmental allergens are also implicated in AD pathogenesis, with a bias towards Th2 immune responses. In particular, dendritic cells expressing membrane IgE receptors play a critical role in the amplification of allergen-specific T cell responses. Cross-linkage of specific IgE receptors on dermal mast cells provokes the release and synthesis of a vast series of mediators. Following their recruitment and activation into the skin, eosinophils are also thought to contribute relevantly to tissue damage. Thus, a complex network of cytokines and chemokines contributes to establishing a local milieu that favors the permanence of inflammation in AD skin. PMID- 11197605 TI - Recent advances in understanding how interleukin 13 signals are involved in the pathogenesis of bronchial asthma. AB - The prevalence of allergic disease has dramatically increased in recent decades, especially in urban and industrialized areas. Allergic diseases are disorders of the immune system, the results of complex interactions among various genetic and environmental factors. Among them, the important role of interleukin 13 (IL-13), a Th2-type cytokine, has recently emerged in the pathogenesis of bronchial asthma. Based on studies using mice, great attention has been paid to the direct effects of IL-13 on bronchial tissues. In this review, we describe recent advances in understanding the signal transduction mechanism of IL-13, the involvement of IL-13 signal-related genes as genetic factors in the pathogenesis of bronchial asthma, and the expression of IL-13 receptor on bronchial tissues. We describe potential strategies for targeting IL-13 signals to improve allergic states. PMID- 11197606 TI - The inflammatory response in Mycobacterium tuberculosis infection. AB - Infection with Mycobacterium tuberculosis (MTB) is accompanied by an intense local inflammatory response which may be critical to the pathogenesis of tuberculosis. Activation of components of the innate immune response, such as recruitment of polymorphonuclear (PMN) and mononuclear phagocytes and induction of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha), by MTB occurs early after MTB infection, however, may persist as the organism establishes itself within granulomas. MTB and its protein and non-protein components are potent in induction of cytokines and chemokines from PMN and monocytes. This review focuses on the interaction of MTB and the host with regard to activation of the innate immune response. It also attempts to identify the potential impact of this early response on the subsequent pathogenesis of MTB, and its role in development and extent of tuberculosis. Insights into the initiation and persistent of the inflammatory response may allow the application of anti-inflammatory agents as adjuncts in the treatment of tuberculosis. PMID- 11197608 TI - The therapeutic potential of interleukin 10 in infection and inflammation. AB - Interleukin 10 (IL-10), a cytokine with inhibitory activity on inflammation and cell-mediated immune responses, holds enormous potential for the treatment of inflammatory and autoimmune disorders. In addition, IL-10 has also been implicated in the immunopathogenesis of a number of infectious diseases through the use of IL-10 knock-out or IL-10 transgenic mouse models. In this review, we delineate infectious and inflammatory conditions in which IL-10 has shown potential for therapeutic manipulation. Specifically, we review the role of IL-10 in human endotoxemia/sepsis and in HIV infection, conditions for which preliminary phase I trials have recently been undertaken. It is suggested that the therapeutic potential of IL-10 to selectively ameliorate human infectious and inflammatory processes can be realized through a careful selection of the clinical conditions in which patients are undergoing concomitant treatment with anti-microbial regimens. PMID- 11197607 TI - Mechanisms of Mycobacterium avium pathogenesis. AB - Infections caused by Mycobacterium avium are common in AIDS patients and patients with chronic lung diseases. The bacterium can be acquired both through the intestinal route and respiratory route. M. avium is capable of invading mucosal epithelial cells and translocating across the mucosa. The bacterium can infect macrophages, interfering with several functions of the host cell. The host defense against M. avium is primarily dependent on CD4+ T lymphocytes and natural killer cells. Activated macrophages can inhibit or kill intracellular bacteria by mechanisms that are currently unknown, but M. avium can invade resting macrophages and suppress key aspects of their function by triggering the release of transforming growth factor beta and interleukin 10. Co-infection with HIV-1 appears to be mutually beneficial, with both organisms growing faster. PMID- 11197609 TI - Idiopathic pulmonary fibrosis: molecular mechanisms and possible therapeutic strategies. AB - Idiopathic pulmonary fibrosis (IPF) is a devastating disease with an almost universally terminal outcome. In recent years much insight has been gained into the pathogenesis of IPF from both a bleomycin mice-model as well as ex vivo human tissue studies. Alveolar damage and inflammation of unknown etiology, eventually leading to interstitial fibrosis, characterize IPF. Apoptosis has emerged as an important factor in the pathogenesis of IPF. This review will outline the current understanding of the immunological and molecular mechanisms underlying IPF and discuss new therapeutic strategies. PMID- 11197610 TI - Bacteriophage therapy of bacterial infections: an update of our institute's experience. AB - 1307 patients with suppurative bacterial infections caused by multidrug-resistant bacteria of different species were treated with specific bacteriophages (BP). BP therapy was highly effective; full recovery was noted in 1123 cases (85.9%). In 134 cases (10.9%) transient improvement was observed and only in 50 cases (3.8%) was BP treatment found to be ineffective. The results confirm the high effectiveness of BP therapy in combating bacterial infections which do not respond to treatment with the available antibiotics. PMID- 11197611 TI - A new diquat derivative appropriate for colourimetric measurements of biological materials in the presence of paraquat. AB - A new colourimetric method is described for the quantification of diquat using a yellow-coloured derivative produced by heating diquat in alkaline solution at 80 degrees C. The absorption maximum of the yellow derivative is 420 nm and the molar absorption coefficient is 2.76 x 10(4) (0.15 in 1 microgram diquat/ml with 1 cm light path). The absorption at 420 nm shows a linear concentration dependence in the range 0.1-10 micrograms/ml and fading of the colour is about 5% after 1 h. Under the same conditions, paraquat does not produce any coloured products. The concentration of diquat in the solution containing both diquat and paraquat can be determined by the absorption of diquat derivative at 420 nm without interference from paraquat. By adding sodium dithionite to the solution the concentration of paraquat can be determined by the absorption of paraquat radicals at 600 nm without interference from diquat, because the yellow derivative does not react with dithionite. This yellow diquat derivative can be extracted completely with cyclohexanol by saturating the solution with Na2SO4. The absorption maximum in cyclohexanol shifts to 440 nm with the same molar absorbance and the same half-band width as in water. Fading of the colour is less than 5% after 24 h in cyclohexanol. Perchloric acid (3%) and trichloroacetic acid (4.5%) which are often used for deproteinization of tissue homogenates, do not inhibit production of the coloured derivative at pH 13.5 or extraction of the derivative with cyclohexanol. This method is suitable for a quick determination of small amounts of diquat in tissues, since the extraction with cyclohexanol not only concentrates the derivative rapidly but also quite efficiently eliminates the coloured substances in tissue homogenates. The detection limit of diquat is 0.02 microgram/ml for blood and 0.05 microgram/g for liver when 1 ml or 1 g is used for analysis. In three human cases of fatal intoxication, both paraquat and diquat were quantified using 50 microliters of serum. In non-toxic dosing of diquat to rats for 14 days, the diquat level was highest in the spleen followed by the kidneys. PMID- 11197612 TI - Suicide in a lions' den. AB - The case of a young man who committed suicide in a lions' den of a zoo is presented. Special attention is paid to the injury pattern which was characterised by numerous penetrating, stab-like wounds and lesions. The remarkable circumstances and history of this incident are most likely connected to a psychological or psychiatric disorder of the victim. PMID- 11197613 TI - Death caused by a letter bomb. AB - A 48-year-old man was killed by the explosion of a letter bomb after receiving severe injuries to his face and left hand. The autopsy ascertained that the right eye and orbit had been completely destroyed by a large piece of metal from a tin can that had entered the cranial cavity through the right eye and caused fatal brain damage. The victim had also sustained a severe injury to his left hand. Reconstruction of the metal and plastic fragments showed that the victim had received a padded envelope with a video cassette in which a simple explosive device was hidden in a flat tin. The explosive charge consisted of a mixture (ca. 60 g) of sodium chlorate, sodium chloride and sucrose. The charge was detonated by a nylon cord attached to the inside of the envelope which was stretched when the video cassette was pulled out of the envelope. This removed a piece of plastic from between two contacts, and the explosion was set off immediately by a battery which activated two flash bulbs placed within the charge. PMID- 11197614 TI - The UV hand lamp as a helpful instrument for macroscopic visualisation of myocardial fibrosis during autopsy. AB - The application of ultraviolet light in forensic practice is a well-tested method to visualise traces or skin alterations. When viewing myocardial sections under UV light at autopsy, bluish-white fluorescent areas became visible that could not be detected in the seemingly homogenous myocardium in daylight. A systematic comparison of the macroscopic cardiac findings and the pertinent histological sections showed that in all cases with a positive UV fluorescence myocardial fibrosis or lipomatosis could be confirmed by histological methods. The examination for UV fluorescence of the myocardium seems to be a simple and rapid method improving the macroscopic perceptibility of fibrotic changes and minor scars. PMID- 11197616 TI - Molecular analysis of the human orosomucoid gene ORM1*Q0koln responsible for incompatibility in a German paternity case. AB - In a German paternity test, an alleged father was excluded only by reverse homozygosity of ORM1 phenotypes (mother ORM1 S, child ORM1 S and alleged father ORM1 F1) out of the 28 classical and DNA markers investigated. Without the ORM1 system the biostatistical probability of paternity was calculated to exceed 99.999%. The intensity of the immunoprinted bands of the ORM1 protein for the child and alleged father after isoelectric focusing appeared to be reduced to about half. To identify a possible null allele, gene-specific amplification followed by single-strand conformation polymorphism and sequencing analyses were carried out. Deletion of one of the two copies of a 4 bp direct repeat sequence (GTCT) in exon 4 of the consensus sequence of ORM1*F1 was observed in the child and alleged father. Thus, the sharing of a rare mutant gene, ORM1*Q0koln, increased the probability of paternity. PMID- 11197615 TI - Genetic diversity of nine STRs in two northwest Iberian populations: Galicia and northern Portugal. AB - The genotyping of two population samples from Galicia and northern Portugal was performed for nine STR loci using a single multiplex reaction with the AmpF/STR Profiler Plus PCR amplification kit which co-amplifies the systems D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820 and the XY homologous gene amelogenin. Allele frequencies for these nine tetranucleotide repeat markers were calculated and no significant differences were observed when comparing these two populations. Conformity with Hardy-Weinberg equilibrium proportions was good for all systems in both samples. The combined power of exclusion was 99.981% and 99.980% in Galicia and northern Portugal, respectively and the combined power of discrimination was greater than 99.999%. Segregation analysis of all loci detected two incompatibilities, one in D3S1358 (out of 112 meioses) and another in D7S820 (out of 104 meioses). Both could be explained by single-step mutations. In general co-amplification was good except for some relatively degraded samples in which poor amplification was observed for the largest STRs. Nevertheless the system is technically robust even when small amounts of template DNA are used and in the addition is highly informative and time-saving. However, caution should be taken in the interpretation of profiles in degraded samples and the apparently high mutation rate of D3S1358 and D7S820 should also be kept in mind. PMID- 11197617 TI - Population genetics of the hypervariable locus D12S391 in Koreans. AB - The hypervariable short tandem repeat (STR) locus D12S391 was investigated in a Korean population and 34 fragments were sequenced to confirm the structure of alleles. From these sequenced fragments an allelic ladder containing 13 sequenced alleles was constructed. From 595 unrelated Koreans, 14 alleles were detected and one variant allele 19.3 was observed. The observed heterozygosity was 0.795 and no deviation from Hardy-Weinberg equilibrium was observed in the Korean population (p = 0.606). The allele frequency distribution in the Korean population was not similar to other racial or ethnic groups except for Egyptians, Yemenis, Japanese and Caucasoids from the Rhine area. No mutations were observed in the 702 meioses from 144 Korean families. This study demonstrates that the STR locus D12S391 is a useful tool for forensic identification and parentage testing. PMID- 11197618 TI - A fatal case of infantile scurvy. AB - We report a case of infant death due to scurvy, which is very rare in Japan. We initially had little knowledge of the disease and suspected that the bleeding in the body was caused by domestic violence. The case did not fall under the category of the battered child syndrome but the death was caused by ignorance with respect to child care. In addition the parents usually locked the child alone in a room during the day and this is probably a case of neglect. PMID- 11197619 TI - Highly informative Y-chromosomal haplotypes by the addition of three new STRs DYS437, DYS438 and DYS439. AB - The Y chromosome STRs DYS437, DYS438 and DYS439 were selected from publicly available genome databases and used to analyse an Italian population sample. A tetraplex PCR reaction including the highly informative DYS385 locus, was set up and used for the analysis of 131 male samples to determine allele frequencies and STR diversity values. The number of different haplotypes and the haplotype diversity value found from the analysis of the STRs included in the tetraplex reaction were very similar to those found from the analysis of the basic set of 7 Y-STRs (DYS19, DYS389I/II, DYS390, DYS391, DYS392 and DYS393) previously carried out on the same population sample. By combining the allelic states of the 11 Y chromosomal STRs we could construct highly informative haplotypes that allowed the discrimination of 93.8% (120 out of 128) of the samples tested. This approach represents a very powerful tool for individual identification and paternity testing in forensic medicine. PMID- 11197620 TI - Mitochondrial DNA sequences for 118 individuals from northeastern Spain. AB - A population database was generated from 118 unrelated Caucasoid individuals living in Spain. Sequence polymorphisms of the mitochondrial DNA (mtDNA) control region, hypervariable regions I and II (HVRI and HVRII) were determined using the polymerase chain reaction (PCR) and direct sequencing. A total of 102 different sequences were found as defined by 105 variable positions. The most common sequence occurred six times, and this sequence is also the most frequent in other European populations such as Austria, Germany and Britain. The mean pair-wise difference for the two HVR regions taken together was 7.74. The study revealed that transitions made up the majority of the variations (88%), whereas we observed a significantly lower frequency of transversions (8%). Also one individual in this study was observed with two positions of heteroplasmy at nucleotides 150 (C/T) and 153 (G/A). A statistical estimate of the results for this population showed a genetic diversity of 0.99. The probability of two random individuals showing identical mtDNA haplotypes is 1.3%. In order to use the mtDNA analysis in forensic casework, we consider that it is of crucial importance to know the frequency of the different sequences of mtDNA, and this data base study could be a useful tool to statistically evaluate the results. PMID- 11197621 TI - Detection of gunshot residues in routine CTs. AB - The forensic assessment of non-fatal gunshot wounds often proves to be difficult as wounds have usually been cleaned and protected with a sterile bandage by the time of the examination. The aim of our investigation was to test the possible application of computed tomography (CT) for the forensic assessment. Doing so raised the questions whether gunshot residues in the soft tissues, detected by means of 3-dimensional CT, can be used as evidence of a close-range shot and whether conclusions can be drawn pertaining to the range of the shot or the type of bullet used based on the distribution of the radiologically detectable material? In this experimental study 39 shots were fired at fresh pig skin and it was possible to distinguish shots fired from distances of more than 10 cm and contact shots independent of the type of bullet. For unjacketed lead bullets, radiopaque material could be seen in the depth of the entrance would for firing distances up to 10 cm. In individual cases, CT data and the 3-D reconstruction could provide valuable information in the forensic assessment of patients with gunshot wounds. PMID- 11197622 TI - Odontological identification of human remains from mass graves in Croatia. AB - This paper reports the results and methods of dental identification of 1000 human remains exhumed from mass graves in Croatia up to July 1998. Personal identification of the victims was performed at the Department of Forensic Medicine and Criminology at the School of Medicine in Zagreb. A forensic odontologist participated in the identification process by carrying out the dental identification. A total of 824 victims were positively identified, while 176 victims remained unidentified. Dental identification based on available dental antemortem data was achieved in 25% of the cases. Dental identification based on dental charts was achieved in 35%, on x-rays in 15%, on photographs of teeth in 22%, on interviews in 18%, and on confirmation by odontologists in 10% of the cases. Teeth, in combination with anthropological parameters, age, sex and height, as well as other specific characteristics such as tattoos, personal identification cards, clothes, jewellery and DNA, were helpful for identification of 64% of the victims, but the significance for the identification was not dominant. Only in 11% of the cases was identification achieved by other relevant means and teeth not used at all. Identification procedures in Croatia will continue until another 1700 people who are still missing or kept as prisoners of war since the aggression on Croatia in 1991 are found and/or identified. PMID- 11197623 TI - Species identification by means of the cytochrome b gene. AB - Species identification was carried out by nucleotide sequence analysis of the cytochrome b (cytb) gene. The aim of the study was to identify biological specimens from diverse vertebrate animals by extracting and amplifying DNA from 44 different animal species covering the 5 major vertebrate groups (i.e. mammals, birds, reptiles, amphibians and fishes). The sequences derived were used to identify the biological origin of the samples by aligning to cytb gene sequence entries in nucleotide databases using the program BLAST. All sequences were submitted to the GenBank including new species which were not observed in the databases. The applicability of this method to the forensic field is demonstrated by simulated casework conditions where different types of samples including problematic specimens such as hair, bone samples, bristles and feathers were investigated to identify the species. PMID- 11197624 TI - Is vitreous humour useful for the interpretation of 3,4 methylenedioxymethamphetamine (MDMA) blood levels? Experimental approach with rabbits. AB - As drug instability and redistribution are factors known to affect the interpretation of post-mortem blood levels, we questioned whether post-mortem vitreous humour concentrations could be useful as predictors for the MDMA load at the time of death. In a first series of in vivo experiments using rabbits, 3,4 methylenedioxymethamphetamine (MDMA) concentrations in plasma, blood and vitreous humour were studied as a function of time after intravenous (i.v.) administration of MDMA. Equilibration between the vascular compartment and vitreous humour was attained about 1 h after i.v. MDMA administration. In a second series of experiments, the post-mortem stability of MDMA in vitreous humour in relation to ambient temperature was investigated. Post-mortem MDMA concentrations in vitreous humour were closer to the ante-mortem blood levels when compared to cardiac blood samples. These preliminary investigations in the rabbit model indicate that measurements of vitreous humour concentrations could also be of interest for predicting the blood concentration at the time of death in humans. PMID- 11197625 TI - Y chromosome STR haplotypes in four populations from northwest Africa. AB - The eight short tandem repeat (STR) polymorphic systems mapping on the male specific region of the human Y chromosome, DYS19, DYS388, DYS389I, DYS389II, DYS390, DYS391, DYS392 and DYS393, were typed in four populations from northwest (NW) Africa (Moroccan Arabs, southern Moroccan Berbers, Saharawis and Mozabites). Allele frequency distributions showed statistically significant differences for all loci among all the populations except for DYS19. Complete typing was obtained for 185 chromosomes, which showed 74 different haplotypes. The two most frequent haplotypes were found in 16.2% and 15.1% of the individuals, although the latter was almost exclusively found in the Mozabites. Locus and haplotype informativeness were measured by means of the gene diversity (D). The haplotype diversity ranged from 0.856 (Mozabites) to 0.967 (southern Moroccan Berbers). For some loci, allele frequencies in NW Africans were clearly different from those in Europeans. The most common NW African haplotype was found only in one individual out of a total of 494 Europeans typed for the whole STR set. Thus, NW African and European Y chromosomes are clearly differentiated. PMID- 11197627 TI - Forensic validation of a multiplex containing nine STRs--population genetics in northern Poland. AB - This paper presents the allele frequency distributions for the nine loci (D3S1358, VWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317 and D7S820) present in the commercially available Profiler Plus kit. DNA samples of 202 individuals from Northern Poland were amplified in a multiplex reaction with subsequent automatic detection using capillary electrophoresis. All loci met the Hardy Weinberg equilibrium conditions. The calculated probability of identity was 2.26 x 10(-11) giving an average probability of identity of 1 in 44 billion. Considerable improvement of analysis precision was observed after substituting the GeneScan 500 for the fluorescent ladder 60-400 bp. The influence of DNA concentration on stutter and artefact formation and the ratio of heterozygote alleles was analysed. PMID- 11197626 TI - A Korean population study of the nine STR loci FGA, VWA, D3S1358, D18S51, D21S11, D8S1179, D7S820, D13S317 and D5S818. AB - DNA typing was performed on 379 randomly selected unrelated Koreans using the nine short tandem repeat loci FGA, VWA, D3S1358, D18S51, D21S11, D8S1179, D7S820, D13S317 and D5S818 present in the AmpF/STR Profiler Plus PCR amplification kit. Allele frequencies, heterozygosity, power of discrimination, mean exclusion chance, and polymorphism information content of each locus were calculated by statistical analysis. All nine loci were in Hardy-Weinberg equilibrium. The combined discrimination index and the combined mean exclusion chance in Koreans was 2.31 x 10(-12) and 0.99983, respectively. By evaluation of 297 children from 128 families, 2 mutations were found at the FGA locus and 1 each at the D18S51 and D13S317 loci. This study demonstrates that this multiplex system is a useful and convenient tool for forensic identification and parentage testing in Korea. PMID- 11197628 TI - Demonstration of myocardial necrosis in the presence of advanced putrefaction. AB - Samples of heart tissue were investigated in two series for the detectability of myocardial necrosis after artificial and natural putrefaction, respectively. In the first series heart tissue with and without infarction was artificially subjected to humid and dry autolysis and putrefaction. In the second investigation heart tissue was obtained from exhumed bodies after periods of burial ranging between 10 and 929 days. Besides histology a variety of immunohistochemical markers were applied and C5b-9 gave positive results even after long periods of artificial and natural putrefaction. From the methods tested, this was by far the most sensitive method with a high robustness against putrefaction. NP57, which indicates neutrophilic leucocytes could be demonstrated considerably longer after humid putrefaction than after dry putrefaction. The time limits of detection were considerably longer than for H&E. These two methods are the methods of choice for the detection of myocardial infarction and leucocyte infiltration in advanced stages of putrefaction. PMID- 11197629 TI - DNA contamination of mortuary instruments and work surfaces: a significant problem in forensic practice? AB - A study of 20 mortuaries was undertaken to assess whether contamination of instruments, tables and cutting areas due to residual material containing human DNA after routine cleaning is an actual or only a theoretical problem. Of the 20 mortuaries studied, 50% were found to have material containing quantifiable human DNA on the instruments and surfaces sampled. This DNA was amplified and found, in some cases, to have been derived from at least three people. Of those that did not yield measurable amounts of DNA, a number of samples were selected at random, amplified and were found to produce partial profiles indicating the presence of low levels of human DNA. The possible sources of human DNA from mortuaries are discussed as well as means to reduce or irradicate the problem of instrument contamination. Finally the implications of these findings for forensic investigations are discussed. PMID- 11197630 TI - Diatom detection in the diagnosis of death by drowning. AB - A medicolegal/algological collaboration lasting several years aimed at developing methods for dealing with dead bodies found in water where the circumstances are not clear, has led to an interdisciplinary procedure. To enable algological analysis, sample preservation and preparation must be free from contamination or carry-over at the beginning of the autopsy, although it should be noted that the demands on the digestion method are very high. One or more water samples from the site of drowning (from surface and bed) should be taken. Microscopic-algological analysis should record quantitative (diatom density), qualitative (species) and morphological (description of diatom valves) details for every sample. Furthermore, the species index and dominance identity similarity indices are calculated during the analysis procedure. The algological conclusions are based primarily on the separation values of Kater as well as on pair-matching. The final report is the result of interdisciplinary collaboration. PMID- 11197631 TI - The probability distribution of the number of loci indicating exclusion in a core set of STR markers. AB - The distribution of the number of loci out of the 13 in the CODIS STR set that would show an exclusion (i.e., a genotype set incompatible either with the prosecution hypothesis or with Mendelian transmission) was estimated in different scenarios. The knowledge of this distribution would provide a framework against which casework evidence can be compared. I used allele frequencies in Iberian and in Italian populations to generate individual genotypes at random and to test in 1 million simulation replicates, how many of the 13 loci would give an exclusion in an individual identification case, a paternity case, and a double parenthood case. All three scenarios were tested under an expected overall exclusion, both for unrelated individuals and for cases in which the suspect or the alleged father was the brother of the real culprit or real father. Paternity and double parenthood cases were also tested in the true scenario, with exclusionary loci due to mutation. In individual identification cases, the average number of exclusionary loci was 11.95 with a minimum of 7. This STR set also showed sufficient power to resolve identification cases in which the evidence sample came from a suspect's sib. False paternity cases yielded an average of 7.65 exclusionary loci and exclusions with only one (0.0108%) or two (0.14%) exclusionary loci were obtained only rarely. The cases of exclusion with one locus could lead to likelihood ratios in favour of paternity, while both true and false paternity cases with two exclusionary loci would often lead to non conclusive likelihood ratios. The average number of exclusionary loci in a paternity case where the alleged father was the real father's brother was 3.82, with a significant number of cases where no exclusions were obtained. PMID- 11197632 TI - Development of haemoglobin subtypes and extramedullary haematopoiesis in young rats. Effects of hypercapnic and hypoxic environment. AB - The influence of repeated hypoxia on the development of haemoglobin (Hb) subtypes and on extramedullary haematopoiesis (EMH) was investigated in young Wistar rats of different ages. The rats were exposed to hypercapnic/hypoxic and to "simple" hypoxic conditions. The results obtained were compared to those of an untreated age-matched control group. Different globin chains were measured using HPLC and time-of-flight (TOF) mass analysis. The number of EMH cells was evaluated by cell counting. By determining the proportions of alpha- and beta-chains, fetal, neonatal and mature types of globin chain composition could be differentiated. The beta-2 chain levels were significantly higher in hypercapnic/hypoxic environments than in the controls and simple hypoxic environments. The numbers of EMH cells in the two groups subjected to hypercapnia/hypoxia decreased significantly more slowly compared to the controls and simple hypoxia groups. Therefore, the development of Hb subtypes and the EMH activity in rats were influenced by both repeated hypercapnia and hypoxia. PMID- 11197633 TI - The calculation of blood ethanol concentrations in males and females. AB - In German-speaking countries, blood ethanol concentrations (BECs) are usually calculated using Widmark's equation. The distribution factor r of this equation is a correction factor needed to obtain a reduced body mass and corresponds to the ratio of total body water and blood water content. To enhance the reliability of Widmark's model equation, the body weight, body height, blood water content and total body water of 256 women and 273 men were measured. The ratio of body water to blood water ranged from 0.44 to 0.80 in women and from 0.60 to 0.87 in men. For both sexes equations were developed by multiple regression analysis which allow the determination of the individual, more realistic distribution factors rFI (for females) and rMI (for males) even when only body height and body weight are known. Drinking experiments revealed a clearly higher congruence of calculated and measured blood ethanol concentrations when rFI or rMI were used instead of rigid distribution factors, i.e. 0.6 for women and 0.7 for men with or without the assumption of a 10% so-called resorption deficit. Additionally, Widmark's equation in combination with rFI or rMI allows a more accurate prediction of blood ethanol concentrations than the equations of Watson and Ulrich. PMID- 11197634 TI - Biostatistics for mixed stains: the case of tested relatives of a non-tested suspect. AB - Analysis of a mixed biological stain by means of highly polymorphic VNTR systems usually reveals a profile composed of multiple markers. If the victim and one or several suspects match the profile, the evidential strength of the matches has to be very carefully analysed. The appropriate methods for the statistical analysis of DNA profiles advanced recently were limited to cases with no relationship between the tested and non-tested persons. The present paper extends the theory beyond this limitation. PMID- 11197635 TI - Quality assurance in age estimation based on aspartic acid racemisation. AB - Estimates of the age of living and dead individuals, obtained in order to answer legal or social questions, require minimum quality standards in order to guarantee data quality. We present an outline strategy (with recommendations) for the attainment of quality assurance in age estimation based on aspartic acid racemisation. The strategy is based on a definition of minimum standards for laboratories, including documentation of procedures, methodology and levels of expertise, and the formulation of guidelines for intralaboratory and interlaboratory quality control. PMID- 11197636 TI - A new pentaplex PCR system for forensic casework analysis. AB - In 1998 the Federal Criminal Police Office of Germany (BKA) established a central genetic database of offenders and suspects to facilitate comparisons with biological samples from future criminal offences. The five obligatory short tandem repeat (STR) loci in this database (TH01, SE33, vWA, FGA and D21S11) were co-amplified in a new PCR pentaplex analysing system together with the sex specific locus amelogenin. Due to overlapping fragment sizes, amplification products were fluorescent dye-labelled with different colours, separated by electrophoresis and detected directly using the ABI PRISM 310 Genetic Analyzer. Reproducible and reliable results were obtained from as low as 125 pg template DNA, indicating high specificity and sensitivity of the assay. Environmental studies and enzymatic digest with DNase I revealed an excellent stability of the pentaplex system with typeable results even in cases of partially degraded DNA. Complete and reproducible DNA typing was possible in blood-stain mixtures with the minor component as low as 10%. Mean stutter peak intensities were analysed for all loci and ranged from 2.7 +/- 0.8% (TH01) to 10.6 +/- 1.6% (vWA) of the main signal intensity. Allele frequencies were determined in a North Bavarian population sample (n = 121). The combination of five systems resulted in a mean exclusion chance of 99.86% and a power of discrimination of 99.999996%. No deviation from Hardy-Weinberg equilibrium could be found. PMID- 11197637 TI - The distribution of laudanosine in tissues after death from atracurium injection. AB - A case is presented involving an acute fatality resulting from self administration of atracurium, a muscle relaxant by a 45-year-old nurse. In the body, atracurium undergoes a spontaneous non-enzymatic degradation to laudanosine and an acrylate moiety. Laudanosine was quantified using gas chromatography coupled to mass spectrometry after extraction with chloroform-isopropanol-n heptane (50:17:33 v/v) at pH 9.5 and separation on a HP5-MS capillary column. Laudanosine was subject to postmortem redistribution due to release from drug rich tissues such as the lung and heart. The heart blood (917 ng/ml) to peripheral blood (390 ng/ml) ratio was 2.4. No other drugs, including ethanol were detected. PMID- 11197638 TI - Postmortem absorption of dichloromethane: a case study and animal experiments. AB - A case of accidental death after occupational exposure to an atmosphere containing dichloromethane (DCM) is reported. The concentrations of DCM in the blood and tissues of a 40-year-old man who died while observing an industrial washing machine filled with DCM vapour were blood 1660 mg/l, urine 247 mg/l, brain 87 mg/kg, heart muscle 199 mg/kg and lungs 103 mg/kg which are 3-7 times higher than previously reported fatal levels. The body was left undiscovered in the machine filled with DCM vapour for about 20 h. The present study was designed to determine whether all the DCM detected in the tissues and body fluids had been inhaled while alive using rats as the experimental model. The concentrations of DCM in the tissues and body fluids of a rat that died from DCM poisoning and was left for 20 h in a box containing DCM vapour were the same as those in the tissues and body fluids of a rat that had died from an injected overdose of barbiturates and had then been placed in the DCM box in a similar manner. Moreover, the concentrations of DCM in the tissues and body fluids of the carcasses that were exposed to the DCM vapour increased gradually throughout the period of exposure. These findings imply that DCM is able to penetrate the tissues and body fluids of rat carcasses through a route other than inhalation such as through the skin. PMID- 11197639 TI - [In Process Citation] PMID- 11197640 TI - Laparoscopic tubal sterilization under spinal anesthesia in the Third World. AB - Adequate family planning options are extremely limited in the third world. Sterilization is desired by many and often unavailable. Quality of life for women and their families in the third world can be greatly improved by making additional family planning options available. This article describes a program to make sterilization available to women of southeastern Dominican Republic. PMID- 11197641 TI - The 2001 General Assembly: a look ahead. PMID- 11197642 TI - Of laws and sausages. PMID- 11197643 TI - May you live in interesting times. PMID- 11197644 TI - [Effect of mineral drinking water on hormonal reactions of rats under hypoxic conditions]. AB - Acute action of hypoxia was modelled by raising 26 Wistar male rats (body mass 230-250 g) in the low-pressure chamber at the height of 9000 m with the speed 15 m/s. The exposure was 60 min. Before and after lifting the rat blood was examined for contents of hormones, glucose and body temperature. It was found that hormonal reactions in maximal hypoxia and in drinking mineral water were virtually the same. This explains potentiation of hypoxia by mineral water. It is suggested that hypoxia and drinking mineral waters should be included in the complex strengthening the reserves of human body. PMID- 11197645 TI - [Effectiveness of magnetotherapy in elderly hypertensive patients aging at different rates]. AB - Effectiveness of general magnetotherapy was studied in 84 patients with essential hypertension and 36 patients with isolated systolic arterial hypertension of old age. It is thought necessary to determine biological age of the cardiovascular system in hypertensive patients over 60 years of age to specify indications and contraindications to physiotherapy. PMID- 11197646 TI - [Principles of rehabilitation of respiratory tract diseases]. AB - The authors propose a conception of rehabilitation after respiratory diseases based on combined action of some nonpharmacological therapeutic factors operating etiologically, symptomatically, pathogenetically and sanogenetically. These rehabilitation methods can be used in persons with respiratory diseases risk factors and for prophylaxis. PMID- 11197647 TI - [Use of low-frequency ultrasound in rehabilitating chronic bronchitis patients]. PMID- 11197648 TI - [Effectiveness of halotherapy of chronic bronchitis patients]. AB - The chemoluminescence test in 49 patients with lingering inflammatory chronic bronchitis has revealed inhibition of generation of active oxygen forms in the whole blood, intensification of lipid peroxidation in the serum, depression of local immunity. Administration of halotherapy to the above patients results in correction of disturbances of free-radical oxidation, improves local immunity and clinical course of the disease. PMID- 11197649 TI - [Physiotherapeutic methods in combined rehabilitation of children with respiratory tract diseases, associated with congential maxillofacial pathology]. PMID- 11197650 TI - [New aspects of rehabilitating patients with post-traumatic defects and deformation of the maxillofacial regions]. AB - Efficacy was compared of local magnetotherapy and electrostimulation in rehabilitation of patients with posttraumatic maxillofacial defects and deformities. A multidirectional mechanism of the two complexes on peripheral and central structures of the maxillofacial region was discovered. PMID- 11197651 TI - [Physiopuncture therapy of trigeminal neuralgia]. AB - 137 patients with typical trifacial neuralgia (TN) were divided into four groups. 30 patients of group 1 received EHF therapy, 30 patients of group 2 were exposed to laser, 67 patients of group 3 were treated with combination of laser with EHF puncture, 10 patients of group 4 were controls on conventional physiotherapy. Patients of all the groups were given drug of choice--carbamazepin. The highest response was registered in group 3, 21(31.3%) patients of which could stop carbamazepin, while 40(59.7%) patients reduced carbamazepin dose by 50-70%. Positive results were due to restoration of self-regulation in pain and antipain systems which are disturbed in TN patients. PMID- 11197652 TI - [Low-frequency ultrasound: effect on the body, therapeutic use, and prospects for investigation]. AB - The paper concerns characteristics and mechanisms of action of low-frequency ultrasound, indications for its use and prospects for the future. PMID- 11197653 TI - [Experience in using a subtonal frequency current for analgesia after gynecologic operations on adolescents]. AB - High antipain effectiveness of early (within 36 postoperative hours) application of supratonal frequency after urgent operations on the ovaries was established after testing in 21 girls (mean age 13.0 +/- 0.5 years). PMID- 11197654 TI - [Use of super-high frequency electromagnetic fields on intrarenal circulation and morphological status of health kidneys (experimental study)]. AB - The experimental study investigated action of electromagnetic waves (84 mW/cm2 and 395 mW/cm2) on functional-morphological features of healthy kidney of female rats. A marked hemodynamic effect of decimetric waves is shown which operates via stimulation of intermediary zone with redistribution of intrarenal circulation. Disturbance of circulation occurs in dysregulation of the intrarenal blood flow under overstimulation of the organ circulation with 395 mW/cm2 decimetric waves. This entails disorders of hemodynamics, flebostasis, stromal edema, dystrophy of tubular epithelium, periglomerular sclerosis causing aseptic interstitial inflammation. This is also proved by levels of prostaglandin E2 in tissue of renal papillae. These findings should be considered in administration of decimetric waves in patients with renal inflammation. PMID- 11197655 TI - [Photophoresis of oxolin ointment in combined therapy of patients with chronic relapsing aphthous stomatitis]. AB - Significant improvement of microcirculation and tissue immunity was found in 75 patients with chronic recurrent aphtous stomatitis treated with photophoresis of 0.25% oxolin ointment on the site of the disease focus. PMID- 11197656 TI - [Features of reaction of the cardiorespiratory system in patients with chronic obstructive bronchitis during speleotherapy]. PMID- 11197657 TI - [Combined use of transcerebral electrostimulation and the "Defensor" traction system in treating patients with lumbar radiculitis]. PMID- 11197658 TI - [Effect of low-intensity laser radiation on the ratio of various fractions of prostaglandins in patients' blood after hemorrhoidectomy]. PMID- 11197659 TI - [Rehabilitation of children with insulin-dependent diabetes mellitus in a local sanitorium]. PMID- 11197660 TI - [Requirement for studying therapeutic mud deposits. Scope and kinds of mud resource assessments]. PMID- 11197661 TI - [Use of the recuperative "antistress" program in a general hospital]. PMID- 11197662 TI - [History of the Central Institute of Sanitorium Treatment]. PMID- 11197663 TI - [Experimental study of the effect of pulsed infrared laser radiation on skeletal muscle regeneration after mechanical trauma]. AB - Impulse infrared laser radiation (0.89 microm) was examined for effect on regeneration of cross-cut musculus gastrocnemius in adult rats (ten 3-min exposures, 2-3 procedures weekly for one month after the operation, modulating frequency 10 Hz, total course dose 3.6 J/cm2). Histological, morphometric and biochemical parameters of muscular regenerates as well as biochemical serum indices show enhanced regeneration of the skeletal muscle. Formation of the muscular organ ends earlier vs untreated muscles. This was accompanied with more active sclerotization of the muscular regenerate. PMID- 11197664 TI - Motion adaptive x-ray therapy: a feasibility study. AB - Intrafraction motion caused by breathing requires increased treatment margins for chest and abdominal radiotherapy and may lead to 'motion artefacts' in dose distributions during intensity modulated radiotherapy (IMRT). Technologies such as gated radiotherapy may significantly increase the treatment time, while breath hold techniques may be poorly tolerated by pulmonarily compromised patients. A solution that allows reduced margins and dose distribution artefacts, without compromising delivery time, is to synchronously follow the target motion by adapting the x-ray beam using a dynamic multileaf collimator (MLC), i.e. motion adaptive x-ray therapy, or MAX-T for short. Though the target is moving with time, in the MAX-T beam view the target is static. The MAX-T method superimposes the target motion due to respiration onto the beam originally planned for delivery. Thus during beam delivery the beam is dynamically changing position with respect to the isocentre using a dynamic MLC, the leaf positions of which are dependent upon the target position. Synchronization of the MLC motion and target motion occurs using respiration gated radiotherapy equipment. The concept and feasibility of MAX-T and the capability of the treatment machine to deliver such a treatment were investigated by performing measurements for uniform and IMRT fields using a mechanical sinusoidal oscillator to simulate target motion. Target dose measurements obtained using MAX-T for a moving target were found to be equivalent to those delivered to a static target by a static beam. PMID- 11197665 TI - A global optimization method for three-dimensional conformal radiotherapy treatment planning. AB - Multiple local minima exist in almost every coplanar or non-coplanar radiotherapy treatment planning problem. We used a global optimization method based on topographical information about the distribution of local minima to find all local minima and select the best as the global minimum. We uniformly select N random points from search regions and construct a topographical graph, from which M (M << N) starting points are selected to launch a local search. Because every seed point was at or near the local minimum, the solutions found by the local search could be used as the final optimization results. We verified this algorithm by applying it to three different clinical cases and comparing the results with those obtained by a local optimization method (sequential quadratic programming). The results show that this algorithm is feasible and efficient. PMID- 11197666 TI - A method to incorporate leakage and head scatter corrections into a tomotherapy inverse treatment planning algorithm. AB - A detailed tomotherapy inverse treatment planning method is described which incorporates leakage and head scatter corrections during each iteration of the optimization process, allowing these effects to be directly accounted for in the optimized dose distribution. It is shown that the conventional inverse planning method for optimizing incident intensity can be extended to include a 'concurrent' leaf sequencing operation from which the leakage and head scatter corrections are determined. The method is demonstrated using the steepest-descent optimization technique with constant step size and a least-squared error objective. The method was implemented using the MATLAB scientific programming environment and its feasibility demonstrated for 2D test cases simulating treatment delivery using a single coplanar rotation. The results indicate that this modification does not significantly affect convergence of the intensity optimization method when exposure times of individual leaves are stratified to a large number of levels (>100) during leaf sequencing. In general, the addition of aperture dependent corrections, especially 'head scatter', reduces incident fluence in local regions of the modulated fan beam, resulting in increased exposure times for individual collimator leaves. These local variations can result in 5% or greater local variation in the optimized dose distribution compared to the uncorrected case. The overall efficiency of the modified intensity optimization algorithm is comparable to that of the original unmodified case. PMID- 11197667 TI - Experimental verification of improved depth-dose distribution using hyper-thermal neutron incidence in neutron capture therapy. AB - We have proposed the utilization of 'hyper-thermal neutrons' for neutron capture therapy (NCT) from the viewpoint of the improvement in the dose distribution in a human body. In order to verify the improved depth-dose distribution due to hyper thermal neutron incidence, two experiments were carried out using a test-type hyper-thermal neutron generator at a thermal neutron irradiation field in Kyoto University Reactor (KUR), which is actually utilized for NCT clinical irradiation. From the free-in-air experiment for the spectrum-shift characteristics, it was confirmed that the hyper-thermal neutrons of approximately 860 K at maximum could be obtained by the generator. From the phantom experiment, the improvement effect and the controllability for the depth dose distribution were confirmed. For example, it was found that the relative neutron depth-dose distribution was about 1 cm improved with the 860 K hyper thermal neutron incidence, compared to the normal thermal neutron incidence. PMID- 11197668 TI - Anisotropy functions for low energy interstitial brachytherapy sources: an EGS4 Monte Carlo study. AB - Anisotropy functions for low energy interstitial brachytherapy sources are examined. Absolute dose rates around 103Pd seed model 200 and 125I seed models 6702 and 6711 have been estimated by means of the EGS4 Monte Carlo simulation system. The DLC-136/PHOTX cross section library, water molecular form factors, bound Compton scattering and Doppler broadening of the Compton-scattered photon energy were considered in the calculations. Following the formalism developed by the Interstitial Brachytherapy Collaborative Working Group, anisotropy functions, F(r, theta), have been calculated. Our Monte Carlo results were compared against a limited set of measured data selected from the literature and other Monte Carlo results. Binding corrections and phantom material selection have been found to have no influence on the anisotropy function. The accuracy of the geometrical source models used for the Monte Carlo calculations was validated against experimental measurements of in-air relative fluence at 100 cm from the source. More detailed knowledge about the geometrical design of 103Pd seed model 200 is needed in order to improve the agreement with experimentally measured in-air fluence. Values for in-air fluence of 125I model 6702 are sensitive to source position within the inner seed cylinder. Excellent agreement between calculated and measured in-air fluence is found for 125I model 6711. It was observed that using in-air relative fluence at 100 cm from the source to calculate the anisotropy function yields a less anisotropic dose distribution at distances close to the source than full Monte Carlo simulation, in contradiction with experimental data. Our results have estimated statistical uncertainties of 1%-3% at the 1sigma level within clinically relevant regions, but contain systematic uncertainties related to the assumed geometrical details. PMID- 11197669 TI - Characterization of monomer/crosslinker consumption and polymer formation observed in FT-Raman spectra of irradiated polyacrylamide gels. AB - Fourier transform Raman spectroscopy was undertaken in the study of irradiated polyacrylamide gels (PAGs) used in 3D radiation dosimetry. By employing correlation techniques, monomer and crosslinker consumption were characterized in the spectra as a function of absorbed dose. The consumption of both monomer and crosslinker is monoexponential up to 13 Gy, although the rates of consumption differ for the two molecules. A sensitivity parameter, D0, in the exponential function has been used to characterize this difference. Up to 13 Gy, D0(acr) = 12 +/- 2 Gy while D0(bis) = 8.0 +/- 0.5 Gy, indicating that bis is consumed at a greater rate than acrylamide and that bis is the limiting factor in the onset of gel saturation, for a gel composition of 6% by weight total monomer (6%T) and where 3% of the total monomer is crosslinker (50%C). Direct evidence of polymer formation was observed in the Raman spectra of irradiated PAG. Polymer formation is monoexponential to a dose of 13 Gy, with a sensitivity parameter of D0(poly) = 14 +/- 2 Gy. This is in good agreement with the consumption rate of acrylamide. The exponential nature of the polymer formation observed here is compared with existing MRI and x-ray CT dose response measurements previously reported to be linear. The results confirm previous studies indicating that Raman spectroscopy provides a direct and useful tool for characterization of irradiated PAG. PMID- 11197670 TI - Optical properties of porcine skin dermis between 900 nm and 1500 nm. AB - The weak absorption of shortwave infrared light by skin tissues between 700 and 1500 nm offers an important window for diagnosis by optical means. The strong scattering of shortwave infrared light by the skin, however, presents a challenge to the modelling of light propagation through the skin and the understanding of skin optics. We have measured the collimated and diffuse transmittance and diffuse reflectance of porcine skin dermis samples within 30 h post-mortem. Monte Carlo simulations have been performed to inversely determine the absorption coefficient, scattering coefficient and anisotropy factor of the dermis samples in the spectral range from 900 to 1500 nm. We further analyse the sensitivity of the values of the parameters to the experimental errors and inverse calculation procedures. The state of the cellular integrity of the skin samples following optical measurements was verified using transmission electron microscopy. These results were correlated to study post-mortem effects on the in vitro optical properties of porcine dermis. We concluded that for samples stored within crushed ice for up to 30 h post-mortem the wavelength dependence of optical properties of the dermis remains unchanged while the values of the parameters vary moderately due to modification of the water content of the tissue. PMID- 11197671 TI - High-resolution SAR modelling for regional hyperthermia: testing quasistatic zooming at 10 MHz. AB - Present-day regional hyperthermia treatment planning systems are limited to centimetre resolution. To obtain CT-resolution SAR distributions, a method called quasistatic zooming has been developed: using the centimetre-resolution E-field distribution and the CT-resolution tomogram, the CT-resolution SAR distribution is obtained. For a low frequency of 10 MHz this method has been validated sucessfully using CT-resolution SAR computations. It appears that these CT resolution SAR distributions are completely different from centimetre-resolution SAR distributions, indicating the necessity for high-resolution SAR modelling. Using the presented zooming technique, reliable CT-resolution SAR modelling is now possible with relatively short computation times. So far, the zooming method has only been validated for low frequencies, but clinically relevant frequencies appear to be possible. PMID- 11197672 TI - Changes in dielectric properties of ex vivo bovine liver at 915 MHz during heating. AB - We have developed a coaxial measurement system for determining the time and temperature dependence of the dielectric properties of bovine liver at 915 MHz during heating. Our data suggest that changes in dielectric properties due to heating are dominated by the relaxation response of two tissue components: tissue water and proteins. At temperatures above 60 degrees C, the effects of these two components contribute to increases of up to 100% and 5% in the values of conductivity and permittivity respectively. Changes due to tissue water content were found to be reversible with temperature, while changes due to protein denaturation were found to be permanent. The temperature coefficients for reversible changes were found to be 1.82 +/- 0.28% degrees C(-1) and -0.130 +/- (5.9 x 10(-2))% degrees C(-1) for conductivity and permittivity respectively. The critical temperatures and activation energies leading to irreversible changes in conductivity and permittivity were determined using Arrhenius analysis. Frequency factors of (1.14 +/- 0.27) x 10(43) s(-1) and (1.95 +/- 0.49) x 10(36) s(-1) were determined for permittivity and conductivity respectively. The activation energies were calculated to be 70.7 +/- 15.8 kcal mol(-1) for permittivity and 60.1 +/- 14.0 kcal mol(-1) for conductivity. PMID- 11197673 TI - Analysis of the influence of the cell geometry, orientation and cell proximity effects on the electric field distribution from direct RF exposure. AB - This paper shows the importance of using a cell model with the proper geometry, orientation and internal structure to study possible cellular effects from direct radiofrequency exposure. For this purpose, the electric field intensity is calculated, using the finite element numerical technique, in single- and multilayer spherical, cylindrical and ellipsoidal mammalian cell models exposed to linearly polarized electromagnetic plane waves of frequencies 900 and 2450 MHz. An extensive analysis is performed on the influence that the cell geometry and orientation with respect to the external field have in the value of the electric field induced in the membrane and cytoplasm. We also show the significant role that the cytoplasmic and extracellular bound water layers play in determining the electric field intensity for the cylindrical and ellipsoidal cell models. Finally, a study of the mutual interactions between cells shows that polarizing effects between cells significantly modify the values of field intensity within the cell. PMID- 11197674 TI - X-ray image intensifier performance and patient doses for combinations of supplemental beam filters and vascular contrast agents. AB - We present an investigation of the fluoroscopic imaging and dosimetric performances of iodine- and gadolinium-based vascular contrast agents in combination with K-absorption edge filters of atomic numbers between 50 (tin) and 82 (lead). These combinations were studied using a theoretical model for a range of diagnostic x-ray spectra (55 to 100 kVp) and for water phantoms representative of thin and thick anatomies. Performance was characterized by radiographic contrast, a derived image quality index, the patient integral and entrance skin doses, and the x-ray tube load. For a given thickness of anatomy, an optimum combination of spectrum kVp, contrast agent and supplemental filter was defined by maximum imaging performance for a minimum or tolerable x-ray tube load and patient dose. It was possible to both improve imaging performance and reduce dose by the use of an appropriate combination of spectrum kVp and filter. For gadolinium-based contrast, performance was optimized with tungsten filtration at 90 kVp for both thin and thick anatomies. It was not possible, however, to optimize the iodinated contrast performance with a single combination of supplemental filter and spectrum kVp. The optimal performance for iodinated contrast was achieved with gadolinium filtration at 60 kVp for thin anatomy and with ytterbium filtration at 80 kVp for thick anatomy. The best performance for thin anatomy was that of the combination of iodinated contrast/gadolinium filter at 60 kVp and the best performance for thick anatomy was that of the combination of gadolinium-based contrast/tungsten filter at 90 kVp. PMID- 11197675 TI - Development of an MR-compatible, rotation-insensitive, annular pressure sensor. AB - There is a growing interest in performing intravascular interventions guided by MR imaging--a technique which offers the possibility of flow measurements during the intervention. For a reliable assessment of the haemodynamic significance of a stenosis, the flow and the pressure decay within the stenosis should both be measured. We have developed an optical, MR-compatible, pressure sensor (Annupres) that uses a novel annular element. Existing optical pressure sensors measure pressures unilaterally, thus giving rise to artefacts because of the dependence of the measurement on the angular orientation of the aperture. The annular element, however, measures blood pressure on all sides, and we show that by using circularly polarized light this pressure measurement is intrinsically insensitive to rotation of the sensor around its long axis. The Annupres sensor has been tested in an experimental set-up, and was able to measure pressures from 50 mmHg to 180 mmHg reliably with an accuracy of 1.5%. PMID- 11197676 TI - Application of anisotropic diffusion to digital enhancement of portal images. AB - We propose the use of anisotropic diffusion filtering to remedy difficulties in analysis of electronic portal images, stemming from their low contrast and high noise levels. Anisotropic diffusion is a nonlinear filter based on the numerical solution to the partial differential equation describing the process of diffusion. In this study we show that this filter is capable of greatly reducing noise in homogeneous areas of portal images while preserving the edges and contrast associated with anatomical features. We also demonstrate that the application of anisotropic diffusion leads to more consistent and reproducible visual extraction of features from portal images. PMID- 11197677 TI - The effect of measurement location on tibia lead XRF measurement results and uncertainty. AB - The aims of this study were to determine whether the location on the tibia measured by 109Cd-based K-shell x-ray fluorescence (XRF) affected the measurement result and its uncertainty, and whether higher tibia lead levels at the extremities of the tibia and/or inhomogeneity in the distribution of lead in the tibia could be inferred therefrom. Replicate XRF measurements were performed at multiple locations on ten adult cadaver intact legs and on nine bare tibiae dissected from them. Mean lead levels in the bare tibiae ranged from 16 to 48 microg Pb per g of bone mineral. Bare tibia measurements showed that both the XRF result and its uncertainty increased towards the proximal and distal ends of the tibia. The XRF result decreased away from the medial-lateral mid-point of the tibia, but XRF uncertainty was not significantly affected. Intact leg measurements showed no effect of proximal distal location on XRF result but did show an effect on XRF uncertainty. We conclude that the XRF method used can determine the differences in bone lead level resulting from the more trabecular composition at the ends of the tibia, and we present limited evidence for localized regions of low tibia lead level. PMID- 11197678 TI - Non-invasive and quantitative near-infrared haemoglobin spectrometry in the piglet brain during hypoxic stress, using a frequency-domain multidistance instrument. AB - The frequency-domain multiple-distance (FDMD) method is capable of measuring the absolute absorption and reduced scattering coefficients of optically turbid media. Absolute measurement of absorption at two near-infrared (NIR) wavelengths makes possible the quantitation of tissue haemoglobin concentration and tissue haemoglobin oxygen-saturation (StO2). However, errors are introduced by the uncertainties of background absorption and the dissimilarities between real tissues and the simplified mathematical model on which these measurements are based. An FDMD-based tissue instrument has been used for the monitoring of tissue haemoglobin concentration and oxygenation in the brain of newborn piglets during periods of hypoxia and hyperoxia. These tissue haemoglobin saturation values were compared with arterial saturation (SaO2) and venous saturation (SvO2) measured by blood gas analyses. A linear correlation was observed between StO2 and the average of SaO2 and SvO2. However, StO2 is not equal to any fixed weighted average of SaO2 and SvO2 unless we introduce an effective background tissue absorption. The magnitude of the background absorption was about 0.08 cm(-1) at 758 nm and 0.06 cm(-1) at 830 nm, and it was nearly consistent between piglets. The origin of this 'effective' background absorption may be real, an artefact caused by the application of a simplified model to a complex sample, or a combination of factors. PMID- 11197679 TI - Automated counting of mammalian cell colonies. AB - Investigating the effect of low-dose radiation exposure on cells using assays of colony-forming ability requires large cell samples to maintain statistical accuracy. Manually counting the resulting colonies is a laborious task in which consistent objectivity is hard to achieve. This is true especially with some mammalian cell lines which form poorly defined or 'fuzzy' colonies, typified by glioma or fibroblast cell lines. A computer-vision-based automated colony counter is presented in this paper. It utilizes novel imaging and image-processing methods involving a modified form of the Hough transform. The automated counter is able to identify less-discrete cell colonies typical of these cell lines. The results of automated colony counting are compared with those from four manual (human) colony counts for the cell lines HT29, A172, U118 and IN1265. The results from the automated counts fall well within the distribution of the manual counts for all four cell lines with respect to surviving fraction (SF) versus dose curves, SF values at 2 Gy (SF2) and total area under the SF curve (Dbar). From the variation in the counts, it is shown that the automated counts are generally more consistent than the manual counts. PMID- 11197680 TI - Evaluation of inverse methods and head models for EEG source localization using a human skull phantom. AB - We used a real-skull phantom head to investigate the performances of representative methods for EEG source localization when considering various head models. We describe several experiments using a montage with current sources located at multiple positions and orientations inside a human skull filled with a conductive medium. The robustness of selected methods based on distributed source models is evaluated as various solutions to the forward problem (from the sphere to the finite element method) are considered. Experimental results indicate that inverse methods using appropriate cortex-based source models are almost always able to locate the active source with excellent precision, with little or no spurious activity in close or distant regions, even when two sources are simultaneously active. Superior regularization schemes for solving the inverse problem can dramatically help the estimation of sparse and focal active zones, despite significant approximation of the head geometry and the conductivity properties of the head tissues. Realistic head models are necessary, though, to fit the data with a reasonable level of residual variance. PMID- 11197681 TI - Operational characteristics of a prototype x-ray needle device. AB - A prototype x-ray needle, which emits 62.5 kVp x-rays at the tip of a 20 cm long, 4 mm diameter steel needle, has been developed by Titan Pulse Sciences Incorporated (PSI) (Albuquerque, NM) and was tested for its suitability in brachytherapy applications in comparison with a similar device by the Photoelectron Corporation. The depth dose profiles were also compared with those of two common brachytherapy sources (125I and 192Ir). The depth dose characteristics of the radiation were comparable with the two brachytherapy sources with a slightly reduced attenuation gradient. The dose rate from the x ray needle tip was relatively isotropic at the needle tip and was continuously adjustable over the range of 0 cGy min(-1) to upwards of 62 cGy min(-1) at a reference distance of 1 cm in air. We detected a significant proportion of x-rays generated along the needle shaft, and not at the needle tip, as intended. The energy spectrum emitted from this device had a peak intensity at 21 keV and an average energy of 28 keV. The beam was attenuated in both aluminium (the first half-value layer being less than 0.1 mm) and in water (50% dose at approximately 2 mm). These studies confirm that although there is potential for a system similar to this one for clinical applications, the simplistic electron guidance used in this particular prototype device limits it to research applications. Further optimization is required in focusing and steering the electron beam to the target, improving x-ray production efficiency and using x-ray target cooling to achieve higher dose rates. PMID- 11197682 TI - An algorithm for stereotactic localization by computed tomography or magnetic resonance imaging. AB - Stereotactic localization of an intracranial lesion by computed tomography or magnetic resonance imaging requires the use of a head frame that is fixed to the skull of the patient. To such head frames are attached either N-shaped or V shaped localization rods. Because of patient positioning, the transverse imaging slices may not be parallel to the frame base; a coordinate transformation algorithm that takes this possibility into consideration is crucial. Here we propose such an algorithm for a head frame with V-shaped localization rods. Our algorithm determines the transformation matrix between the image coordinate system of a transverse image and the frame coordinate system. The determining procedure has three steps: (a) calculation of the oblique angles of a transverse image relative to the head frame and calculation of the image magnification factor; (b) determination of the coordinates of four central markers in both coordinate systems; and (c) determination of the 3 x 3 transformation matrix by using the coordinates of the four markers. This algorithm is robust in principle and is useful for improving the accuracy of localization. PMID- 11197683 TI - Determination of isocentric machine parameters for inclined treatment volumes: a single solution for angled transverse or coronal treatment planes. AB - The derivation of the trigonometric equations necessary to calculate gantry, floor and collimator settings for a treatment plane at an angle phi to the transverse plane of the patient has been described previously. The derivation of a second set of equations to facilitate treatment in a plane at an angle phi to the coronal plane has also been described previously. This work reinterprets the geometry of inclined volumes and shows that essentially only one set of equations is required to determine the settings for treatment planes at an angle phi to either the transverse or coronal planes of the patient. PMID- 11197684 TI - A method for determining the alignment accuracy of the treatment table axis at an isocentric irradiation facility. AB - At an isocentric irradiation facility, the rotation axis of the treatment table has to be accurately aligned in vertical orientation to the isocentre, which is usually marked by three perpendicular laser planes. In particular, high precision radiotherapy techniques, such as radiosurgery or intensity modulated radiotherapy, require a higher alignment accuracy of the table axis than routinely specified by the manufacturers. A simple and efficient method is presented to measure the direction and the size of the displacement of the table axis from the isocentre as marked by the lasers. In addition, the inclination of the table axis against the vertical direction can be determined. The measured displacement and inclination provide the required data to correct for possible misalignments of the treatment table axis and to maintain its alignment. Measurements were performed over a period of two years for a treatment table located at the German heavy ion therapy facility. The mean radial distance between the table axis and the isocentre was found to be 0.25 +/- 0.25 mm. The mean inclination of the table axis in the XZ- and YZ-planes was measured to be 0.03 +/- 0.02 degrees and -0.04 +/- 0.01 degrees, respectively. The measurements demonstrate the good alignment of the treatment table over the analysed time period. The described method can be applied to any isocentric irradiation facility, especially including isocentric linear accelerators used for radiosurgery or other high precision irradiation techniques. PMID- 11197685 TI - Radiochromic film dosimetry in water phantoms. AB - Radiochromic film is investigated for use in dosimetry in water phantoms as opposed to solid phantoms. Investigations are performed to measure the penetration rates of water into radiochromic film and to assess the effects on optical density that this penetration causes. The effects of film orientation during irradiation in water are also tested. Results show that only a small penetration rate is seen from water into the film which only affects the outer areas of the film, with penetration being less than 0.5 mm per hour. The optical density measurements of the film at 660 nm remain unchanged in the unaffected regions of the radiochromic film. Minimal effects are seen due to beam orientation in a water phantom as opposed to solid water phantoms in which an overestimation in dose is normally seen for parallel irradiation. Radiochromic film seems to be an adequate detector for dosimetry in a water phantom where high spatial resolution is needed and angle of beam incidence at the point of interest is important. PMID- 11197686 TI - Field equivalence for clinical electron beams. AB - The concept of field equivalence for electron beams is examined using a pencil beam theory applied to circular fields. It is shown that a circular field can be found for a field of any size, shape and energy for which the depth dose distribution is approximately equivalent. The usefulness of the concept in clinical dosimetry is discussed. PMID- 11197687 TI - Genetic control of susceptibility to infection with Mycobacterium tuberculosis in mice. AB - Genetic factors play a key role in host response, disease severity, and ultimate outcome of infection with Mycobacterium tuberculosis in humans. In the mouse, the DBA/2J strain is very susceptible to M. tuberculosis H37Rv infection, while the C57Bl/6J strain is resistant. In DBA/2J, a heavier bacterial burden causes a unique phenotype, that includes very severe and rapidly fatal pulmonary disease with extensive exudation of neutrophils and tissue necrosis, as opposed to slower progressive pulmonary disease characterized by the accumulation of epithelioid macrophages with protective immune and inflammatory responses in C57Bl/6J. To identify the genes responsible for differences in host response to M. tuberculosis in these two strains, 95 animals of an informative (C57Bl/6J x DBA/2J) F2 cross were infected intravenously with M. tuberculosis (1 x 10(5) CFU) and duration of survival was used as a quantitative phenotypic measure of susceptibility in a whole genome scan. Quantitative trait locus analysis (QTL) showed that the genetically controlled susceptibility was multigenic. QTL analysis identified two significant linkages on the distal portion of chromosome 1 (Trl-1, LOD, 4.80) and on the proximal portion of chromosome 7 (Trl-3, LOD, 4.66) that each account for approximately 21% of the phenotypic variance. A third suggestive linkage was identified on the proximal portion of chromosome 3 (Trl-2, LOD, 3.93; additional 18% of the variance). At each locus, homozygosity for the parental C57Bl/6J alleles was associated with increased resistance to infection. These novel mouse loci provide the basis for evaluating a possible association of the corresponding syntenic chromosomal regions in humans with susceptibility to tuberculosis. PMID- 11197688 TI - No evidence for transmission disequilibrium between a new marker at the myelin basic protein locus and multiple sclerosis in French patients. AB - The myelin basic protein (MBP) gene is a candidate locus for susceptibility to multiple sclerosis. Several groups have tested a complex (TGGA)n repeat in the 5' region of this gene for association/linkage with multiple sclerosis, with divergent results. This region of tandem repetitive sequence has been subjected to complex rearrangements, and there is a possibility that alleles of the same size have different internal structures, which reduces the interest of this marker for linkage disequilibrium studies and may at least partly explain the conflicting results obtained so far. To overcome this problem, we isolated a new polymorphic (CA)n repeat within the Golli-MBP locus. The limited number of alleles identified makes this other marker suitable for transmission disequilibrium studies. We tested this marker for linkage with multiple sclerosis, using the transmission-disequilibrium test (TDT) on a sample of 196 nuclear families in which the genotypes of both parents could be unambiguously defined. We found no evidence of transmission disequilibrium between multiple sclerosis and any of the three alleles of this marker, even when the patients were subdivided according to their HLA-DRB1*1501 status. The present data thus provide no evidence for a contribution of the MBP gene to multiple sclerosis susceptibility in French patients. PMID- 11197689 TI - A new type of genetic regulation of allogeneic response. A novel locus on mouse chromosome 4, Alan2 controls MLC reactivity to three different alloantigens: C57BL/10, BALB/c and CBA. AB - The intensity of the mixed lymphocyte response (MLR) depends on the genetic disparity between the donors of responding and stimulating cells. Differences in the major histocompatibility complex (MHC) and Mls1 antigens induce the strongest responses. However, even with comparable incompatibilities in MHC and Mls antigens, some strains of genetically defined mice respond remarkably better than other strains. Apparently other, so far undefined, genetic factors contribute to the magnitude of the MLR. The strain OcB-9 (H2pz) has 87.5% genes from the strain O20/A (O20) and 12.5% genes from strain B10.O20 (both H2pz). In spite of the overal similarity of their genomes, OcB-9 mice differed from O20 mice in response to three different alloantigens C57BL/10 (H2b), BALB/c (H2d) and CBA (H2k). As both O20 and OcB-9 strains carry identical haplotype H2pz, their differences in alloantigen response depend only on non-MHC genes. We analyzed the genetic basis of these strain differences using (OcB-9 x O20)F2 hybrids, and we mapped a novel locus Alan2 (Alloantigen response 2) on chromosome 4 near D4Mit72 that influences the response to all alloantigens tested. This linkage was significant for C57BL/10 and for BALB/c alloantigens (corrected P values 0.0475 and 0.0158, respectively) and highly suggestive for CBA (corrected P = 0.0661). The response to DBA/1 (H2q) alloantigens exhibited a similar pattern but the linkage was not significant. As MLR reflects the recognition phase of transplantation reaction, identification of human counterparts of the Alan genes and a better understanding of the regulation of alloresponsiveness might lead to a better prediction of patients' reactions to allografts and to a more individualized measures to prevent rejection. PMID- 11197690 TI - IL-TIF/IL-22: genomic organization and mapping of the human and mouse genes. AB - IL-TIF is a new cytokine originally identified as a gene induced by IL-9 in murine T lymphocytes, and showing 22% amino acid identity with IL-10. Here, we report the sequence and organization of the mouse and human IL-TIF genes, which both consist of 6 exons spreading over approximately 6 Kb. The IL-TIF gene is a single copy gene in humans, and is located on chromosome 12q15, at 90 Kb from the IFN gamma gene, and at 27 Kb from the AK155 gene, which codes for another IL-10 related cytokine. In the mouse, the IL-TIF gene is located on chromosome 10, also in the same region as the IFN gamma gene. Although it is a single copy gene in BALB/c and DBA/2 mice, the IL-TIF gene is duplicated in other strains such as C57Bl/6, FVB and 129. The two copies, which show 98% nucleotide identity in the coding region, were named IL-TIF alpha and IL-TIF beta. Beside single nucleotide variations, they differ by a 658 nucleotide deletion in IL-TIF beta, including the first non-coding exon and 603 nucleotides from the promoter. A DNA fragment corresponding to this deletion was sufficient to confer IL-9-regulated expression of a luciferase reporter plasmid, suggesting that the IL-TIF beta gene is either differentially regulated, or not expressed at all. PMID- 11197691 TI - Characterization of new polymorphisms in the 5' UTR of the human interleukin-1 receptor type 1 (IL1R1) gene: linkage to type 1 diabetes and correlation to IL 1RI plasma level. AB - The human interleukin-1 type I receptor (IL-1RI) is the signal transducing receptor for IL-1, a principal proinflammatory cytokine, which is cytotoxic to pancreatic islet beta cells. The IL-1RI gene, IL1R1, maps to chromosome 2q12. We have previously examined part of the IL1R1 promoter region and in the present study we further characterized the promoter region demarcating exon 1B and 1C by sequencing and mutation scanning. New sequence was obtained 1762 bp upstream and 1609 bp downstream the known region. Within this sequence, we identified four frequent single nucleotide polymorphisms (SNPs). PCR-based RFLP assays were established and three of the polymorphisms were typed in a Danish Type 1 (insulin dependent) diabetes mellitus (T1DM) family collection comprising 103 simplex and 150 sib-pair affected families. Linkage was evaluated by the sib-TDT (transmission disequilibrium test). One of the polymorphisms, defined by a Hinfl RFLP assay, demonstrated linkage to T1DM, P(sTDT) = 0.026. Random transmission was observed to unaffected offspring from heterozygous parents, P = 0.87. No evidence for positive linkage was seen for the other tested polymorphisms, P = 0.14 and P = 0.21, respectively. To evaluate the possible functional significance of the Hinfl polymorphism, we measured circulating IL-1RI plasma level in 30 T1DM patients and in 30 control subjects--10 with each genotype in both groups. Significant differences in plasma levels in relation to genotype--independent of disease status--were found (P = 0.04). In both diabetic and non-diabetic subjects, the wt/wt genotype correlated with the highest IL-1RI plasma level, whereas the plasma levels were lowest for the mt/mt genotype. PMID- 11197692 TI - New single nucleotide polymorphisms in the coding region of human TNFR2: association with systemic lupus erythematosus. AB - We recently reported the association of the allele coding for Arg at the position 196 (196R: nucleotide [nt] 587G) of tumor necrosis factor receptor 2 (TNFR2, TNF R75) with systemic lupus erythematosus (SLE) in Japanese. In the present study, we completed the variation screening of the entire coding region of TNFR2. Three new single nucleotide polymorphisms within the coding sequence (cSNPs), as well as several variations within the promoter, introns and 3'-untranslated region (3' UTR), were identified. Among the new SNPs, nt168G, a synonymous substitution (K56K), was in tight linkage disequilibrium with nt587G. Two other cSNPs, nt543 (C-->T) (P181P) and nt694 (G-->A) (E232K), were not significantly associated with SLE. Thus, among the non-synonymous cSNPs, only nt587 (T-->G) (M196R) was found to be significantly associated with SLE in Japanese. PMID- 11197693 TI - The NKG2 natural killer cell receptor family: comparative analysis of promoter sequences. AB - The NKG2 receptor family is crucially involved in target cell recognition by natural killer cells and comprises several activating as well as inhibitory family members. We have established approximately 3 kilobases of upstream promoter sequences of the human NKG2-C, -E and -F genes and have carried out a comparative analysis with available NKG2-A sequences. We found extended regions of homology which contain numerous putative transcription factor binding sites conserved in the NKG2 genes. However, variation in Alu insertion among family members has led to promoter structures unique to the respective family members, which could contribute to differences in transcriptional initiation as well as gene-specific regulation. PMID- 11197694 TI - The -403 G-->A promoter polymorphism in the RANTES gene is associated with atopy and asthma. AB - Asthma is a complex inflammatory condition often associated with bronchial hyperreactivity and atopy. Genetic and environmental factors are implicated and several candidate genes have been implicated. Of these, the chemokine RANTES is responsible for the recruitment of inflammatory cells such as eosinophils and T lymphocytes. We have recently identified a polymorphism within the RANTES promoter (-403 G-->A) and have examined its role, using a PCR-RFLP assay, in the development of atopy and asthma in 201 Caucasian subjects. Atopic status was determined using skin prick testing and serum IgE levels. Severity of airway dysfunction was assessed using spirometric measurement (FEV1) and methacholine challenge (PC20). The -403 A allele was associated with an increased susceptibility to both atopy and asthma. Thus, the proportion of subjects carrying this allele was higher in each of atopic non-asthmatics, non-atopic asthmatics and atopic asthmatics compared with non-atopic, non-asthmatic controls. In particular, this allele was associated with skin test positivity but not IgE level. Homozygosity for the -403 A allele conferred a 6.5-fold increased risk of moderate/severe airway obstruction (FEV1 < or = 80% predicted), a marker for established asthma. Our data, whilst preliminary, indicate that the association of RANTES genotype with both atopy and asthma reflect independent effects, suggesting different mechanisms for the role of this chemokine in atopy and development of airway obstruction. PMID- 11197695 TI - Complete primary structure, chromosomal localisation, and definition of polymorphisms of the gene encoding the human interleukin-12 p40 subunit. AB - Owing to the importance of interleukin (IL)-12 in regulating immune responses, we have determined the complete genomic sequence and organization of the gene encoding its p40 subunit. The genomic sequence was determined and was compared to cDNA sequences to derive exon/intron boundaries. Unusually, both the first and last of the eight exons of this gene are not translated. An extensive search identified several polymorphisms in IL-12p40, including repeat elements in introns 2 and 4 and a polymorphic Taql site in the 3'UTR. However, no polymorphisms were found which could result in amino acid substitutions. This finding places constraints on any preferential involvement of alleles of IL-12p40 in contributing to autoimmune, inflammatory or infectious diseases. PMID- 11197696 TI - New variations in human OX40 ligand (CD134L) gene. AB - We found three new variations in the OX40 ligand (OX40L, CD134L) gene and its 5' upstream region. -921 (G-->A) at 5' upstream region, -19 (C-->G) at 5' untranslated region, and 202 + 25 (G-->T) at intron 2 were identified. -921 (G- >A) and 202 + 25 (G-->T) were detected in a substantial proportion of healthy Japanese individuals and were considered to be single nucleotide polymorphisms (SNPs). -19 (C-->G) was detected in only one healthy individual. There was no association between these variations and the presence of rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). PMID- 11197697 TI - Presidential address--the end of the beginning (again!). PMID- 11197698 TI - The future of neuropathology. PMID- 11197699 TI - Honored guest presentation-developments in surgery of posterior circulation aneurysms. PMID- 11197700 TI - Aneurysms requiring extended cranial base approaches. PMID- 11197701 TI - Selecting aneurysms for adequate exposure without extended cranial base approaches: neurovascular decision-making counterpoint. PMID- 11197702 TI - Which aneurysms should be referred for endovascular therapy? PMID- 11197703 TI - Surgery for cerebral gliomas: past, present, and future. PMID- 11197704 TI - Present and future technical developments on aneurysm embolization. Impact on indications and anatomic results. PMID- 11197705 TI - Arteriovenous malformations: indications for stereotactic radiosurgery. PMID- 11197706 TI - Extracranial carotid lesions that should be managed with angioplasty and stenting. PMID- 11197707 TI - Pediatric brain tumors: a contemporary prospectus. PMID- 11197708 TI - Update on craniofacial surgery: the differential diagnosis of lambdoid synostosis/posterior plagiocephaly. AB - There has been an evolution of thought on the diagnosis and treatment of posterior plagiocephaly. Synostotic posterior plagiocephaly (lambdoid synostosis) can be diagnosed and differentiated from non-synostotic posterior plagiocephaly (positional molding) based on specific cosmetic and radiologic criteria. The advent of high-resolution three-dimensional CT analysis of cranial morphology combined with meticulous clinical studies of the two major causes of posterior plagiocephaly has added much to our understanding of this skull deformity. Children with lambdoid synostosis have a trapezoid-shaped skull with posterior displacement of their ipsilateral ear, ipsilateral mastoid bossing, contralateral occipital bossing, and a fused lambdoid suture that appears as a ridge. Children with posterior plagiocephaly without lambdoid synostosis have a characteristic parallelogram-shaped skull with anterior displacement of the ipsilateral ear and ipsilateral frontal bossing. This subject is surrounded in controversy because many of the children in the past thought to have lambdoid synostosis probably did not, based in part on the aforementioned specific criteria. This is an important point, as most patients with posterior plagiocephaly without synostosis will improve without surgery. One should thus be appropriately conservative in the selection of patients for surgery. The majority of infants evaluated at craniofacial clinics presumably have posterior plagiocephaly without synostosis and can be successfully treated with frequent head turning, helmet, or band therapy. Patients with clinically and radiologically proven synostotic posterior plagiocephaly and a severe deformity should undergo craniofacial surgery. The technique of biparieto-occipital craniotomy is safe, simple, and delivers a good cosmetic result. Our postoperative photographic evaluations have shown an immediate, aesthetically pleasing change in the contour of the occiput, which tends to improve with time. PMID- 11197709 TI - Pediatric trauma made simple. AB - At present, similar to the adult, conventional management in the child following TBI appropriately attempts to lessen the second insults that occur after the injury and the effects of the secondary physiologic events. Many of the treatment modalities used for the child after severe TBI have been extrapolated from the adult data, as there is little literature that primarily involves children. Though children as a group overall have a better outcome than adults, there are many factors that influence prognosis in the pediatric population. The age at injury, mechanism of injury, injury severity, multiple trauma, second insults, and/or the extent of secondary injury can all impact on the final outcome. It is clear that many of the poor outcomes observed are best prevented by preventing either the initial impact or the second insults that typically occur following TBI. Interestingly, very young and preschool children have worse outcomes both in mortality and long-term disability than older children and adolescents. The deficits observed are often persistent and severe in the long term even with aggressive management. Continued aggressive intervention to prevent secondary injury and, in the future, mechanistically targeted therapeutic modalities in the acute setting will hopefully improve the mortality rates and functional recovery in these children. PMID- 11197710 TI - Cerebrospinal fluid shunt technology. PMID- 11197711 TI - Congenital malformations of the central nervous system. PMID- 11197712 TI - Moyamoya syndrome: a surgically treatable cause of stroke in the pediatric patient. PMID- 11197713 TI - Indications and outcomes for lobectomy, corpus callosotomy, and hemispherectomy in pediatric neurosurgical patients. PMID- 11197714 TI - Epilepsy surgery in children. PMID- 11197715 TI - Selective dorsal rhizotomy: an excellent therapeutic option for spastic cerebral palsy. PMID- 11197716 TI - Baclofen infusion for spastic cerebral palsy. PMID- 11197717 TI - Developmental glial biology: the key to understanding glial tumors. PMID- 11197718 TI - The biomechanics of lumbar interbody fusion and sagittal plane balance. PMID- 11197719 TI - Posterior lumbar interbody fusion (PLIF): past, present, and future. PMID- 11197720 TI - Posterolateral fusion of the lumbar spine: rationale, indications, techniques, and results. PMID- 11197721 TI - The role of pedicle screw fixation for lumbar spinal stabilization and fusion. PMID- 11197722 TI - Posterior lumbar interbody fusion: indications, techniques, and results. PMID- 11197724 TI - Open anterior lumbar interbody fusion. PMID- 11197723 TI - The role of anterior lumbar interbody allograft bone dowel fusion as an adjunct to posterior segmental lumbar fixation. PMID- 11197725 TI - Laparoscopic anterior lumbar interbody fusion. PMID- 11197726 TI - The biomechanics of interbody fusion and the shortcomings of lumbar fusion with cages and interbody bone dowels. PMID- 11197727 TI - Resident curriculum guidelines for neurosurgery. Congress of Neurological Surgeons Education Committee. PMID- 11197729 TI - The future of pituitary surgery. PMID- 11197728 TI - BEHAB/brevican: an extracellular matrix component associated with invasive glioma. AB - The extracellular matrix (ECM) has a prominent role in many physiological processes, including organ development, wound healing, and neoplastic growth and invasion. In each of these processes, changes in the composition of the matrix can lead to increased cell movement. In this review, we discuss the role of ECM components in glioma invasion, with special emphasis on the brain-specific proteoglycan, Brain-Enriched Hyaluronan Binding (BEHAB)/brevican. PMID- 11197730 TI - Perspective in pituitary adenomas: an end of the century review of tumorigenesis, diagnosis, and treatment. AB - Significant advances have been made in the molecular biological understanding of pituitary tumorigenesis. These advances will have an impact on the gene therapy of pituitary tumors in the coming century. Transsphenoidal surgery remains the mainstay of treatment for the majority of pituitary adenomas, with endoscopic surgery being used at some centers in select patients. Pharmacotherapy of pituitary adenomas has made great strides in the management of prolactinomas and GH-secreting pituitary adenomas. Finally, radiosurgery has become a very important adjuvant therapy in the treatment of hypersecreting pituitary adenomas. PMID- 11197731 TI - Optimism, satisfaction and time perspective in the elderly. AB - In contrast to younger groups, research with the elderly suggest a predominantly present-focused temporal orientation. One aspect of satisfaction, optimism is conceptualized as a form of future perspective. Health psychology generally asserts that health-enhancing messages depend for effect on a person perceiving future benefits to actions taken in the present to enhance health or minimize ill health risk. The extent to which the elderly perceive or value the future should impact on health maintenance behaviors. In a study of eighty-six elderly people, the dominant ways of viewing time coalesced around a variety of present time perspectives. Within-group differences revealed that as people aged, they became less satisfied with life relative to their level of optimism. For the young-old, optimism was positively correlated with satisfaction, but for the oldest-old the variables were negatively associated. Optimism increased with age while satisfaction decreased with age. The decrease in satisfaction is most probably related more to a sense of realism about the tasks of aging than a sense of "death anxiety," or avoidance of the future. As people age, temporal variables become less important in predicting optimism or satisfaction and optimism becomes less important as a predictor of satisfaction. Implications for developing models of health management in the elderly are discussed. PMID- 11197732 TI - Meeting the challenge of raising grandchildren. AB - More grandparents are raising grandchildren than ever before. The predictable problems they experience include a revision of personal goals; learning how growing up has changed since they raised their own children; cooperating with the parent who shares responsibility for child care; monitoring social and academic progress of children; becoming aware of rights and available social services; and arranging periodic relief from the daily demands of their surrogate obligations. Full-time grandparents often rely on support groups for comfort and advice. The advantages and limitations of this approach are examined. Recommendations are made for ways to improve how support groups function so they can achieve their purposes. PMID- 11197733 TI - Sharing of culture: adult grandchildren's perceptions of intergenerational relations. AB - The current study addressed the sharing of traditions, beliefs, and customs (i.e., culture) between grandparents and grandchildren. Two hundred and forty-six adult grandchildren were surveyed on both existing and newly created measures of grandparenting. Results indicated that extent of shared activities, attitudes toward grandparents, and perceptions of cultural sharing were significantly related. Additionally, it was found that minority and female participants were more likely to engage in intergenerational culture sharing and reported more positive statements about this sharing in response to open-ended questions. Findings highlights the importance of cultural sharing to perceptions of grandchild-grandparent relationships. PMID- 11197734 TI - Toward a culturally inclusive understanding of wisdom: historical roots in the East and West. AB - To establish a clearer definition of wisdom as a psychological concept, Western and Eastern historical literatures were reviewed and assessed within a general analytical/synthetic framework. In the West, either in an ancient Egyptian, biblical, or philosophical sense, wisdom had been often identified as a form of analytical ability such as an increase in the knowledge database or an increase in information processing efficiency. By contrast, the Eastern understanding of wisdom, primarily derived from the ancient Vedic text, had been more inclusive, with both analytical and synthetic domains regarded as necessary moments to the whole of wisdom. The inclusive account was also discussed with respect to two important Eastern themes of wisdom: "void" and "codependence." PMID- 11197735 TI - The meaning of life: animism in the classificatory skills of older adults. AB - Seventy-five participants aged from their teens to their seventies were measured on a battery of measures of personality, lifestyle, intelligence, and educational background. These measures were gauged against performance on a measure of animism, in which participants judged twenty-three items (4 alive, 19 non-living) as living or non-living. Although animism errors increased with age, all groups displayed animism errors, thereby contradicting Piaget (1965). Performance is partially explained by fluid intelligence level, but is more plausibly ascribed to progressive loss of what is essentially peripheral information to non-academic people. PMID- 11197736 TI - From the rotating drum dialyzer to the personal hemodialysis system: a brief history of hemodialysis technology. PMID- 11197737 TI - The role of plasmapheresis in the treatment of focal segmental glomerulosclerosis (FSGS). PMID- 11197738 TI - Recombinant human growth hormone therapy in adult dialysis patients. PMID- 11197739 TI - Nosocomial transmission of hepatitis C virus infection in hemodialysis patients: clinical perspectives. PMID- 11197740 TI - Optimized growth conditions for tissue engineering of human cardiovascular structures. AB - Optimized in vitro formation of strong tissue is a prerequisite for tissue engineering of cardiovascular structures, such as heart valves and blood vessels. This study evaluates different growth media additives as to cell proliferation, extracellular matrix formation, and mechanical characteristics. Biodegradable polymers were seeded with human vascular myofibroblasts. Group A was cultured with standard medium, groups B, C, and D were in addition supplemented with ascorbate, fibroblast growth factor (bFGF), and both respectively. Analysis included histology, electron microsocopy, mechanical testing, and biochemical assays for cell proliferation (DNA) and extracellular matrix (collagen). DNA content increased in all groups, showing significantly more cells in group C and D after 14d. Collagen increased in all groups, except for C. Morphology showed viable, layered cellular tissue, with collagen fibrils after 2w, most pronounced in B and D. Mechanical properties decreased initially, stabilizing after 2w. In conclusion, standard nutrient media were efficient for seeded human vascular cells cultured on biodegradable meshes. Supplementation with bFGF+ascorbate resulted in enhanced early cell proliferation and structurally more mature tissue formation. PMID- 11197741 TI - Biomaterials in spinal fixation. An experimental animal study to improve the performance. AB - Different pedicle screws were biomechanically and morphologically studied and compared through the use of an animal model to determine their efficacy and resistance in spinal fixation. The principal objective was to compare biomechanical and histomorphological aspects of HA-coated screws to uncoated ones. Fourty-eight cylindrical transpedicular self-tapping screws divided into three groups of sixteen each were employed; Group A: stainless steel screws; Group B: titanium screws; Group C: HA-coated titanium screws. The screws were implanted bilaterally and randomly into the L3, L4, and L5 pedicles of eight adult mongrel sheep. The final insertion torque was measured in all the implants. After one and four months, upon euthanization, four samples per group were extracted from the surrounding bone and the screw extraction torque was measured. The remaining samples were examined and processed for histological and histomorphological evaluations. No differences were observed at one month among the extraction torque of the three groups. After four months the only significance between insertion and extraction values was for the HA group, i.e. p=0.001. Comparing the extraction torque values of the three groups after four months of healing, the HA-coated group showed a greater than twofold increase (p<0.0005). No differences were observed at one month among the percentages of bone-implant contact in the three groups. After four months the percentage was significant only for the C group (p<0.0005). At four months a correlation was found between the morphological and the biomechanical data of group C (p<0.0005). The use of hydroxyapatite-coated screws could act as an effective method to improve the bone-implant interface, thus obtaining a strong fixation of the implant independently of the arthrodesis achieved with bone graft. PMID- 11197742 TI - Apligraf--a living human skin equivalent for the treatment of chronic wounds. AB - Apligraf, a manufactured living human skin equivalent, was the first true composite tissue analog to become commercially available. It has been approved by the FDA for the treatment of venous leg ulcers and diabetic foot ulcers. The tissue engineered bi-layered skin equivalent has both an epidermis and a dermis, which consist of keratinocytes and fibroblasts derived from neonatal foreskin and bovine collagen. The skin equivalent produces a great number of cytokines and growth factors and is immunologically well tolerated. The product is easy to handle in clinical use and can be applied in an outpatient setting. PMID- 11197743 TI - Therapeutic apheresis in children: experience in a pediatric dialysis center. AB - The use of apheretic procedures in pediatric patients has always been restricted by technical difficulties and the low incidence of diseases requiring this kind of treatment. The aim of the present study was to describe the solutions adopted to solve technical difficulties related to priming, vascular access and monitoring and then to evaluate clinical results. Between 1982 and 2000, 51 consecutive children (28 male, 23 female) with a mean age of 4.9 +/- 4.8 years (3 months-14.8 years) and a mean weight of 19.7 +/- 12.8 kg (5-52 kg), with renal and/or extra-renal diseases requiring apheretic procedures were selected for the study. The overall number of procedures performed were: 226 plasma-exchange (PE), 6 LDL-apheresis (LDL-A) and 8 protein A immunoadsorption (IAPA) sessions. Our therapeutic protocol involves hematic flux of 20-100 ml/min and ultrafiltration of 5-20 ml/min. In each 70-95 minute session we exchanged plasmatic volume with fresh frozen plasma or with a solution of 6% albumin in lactated Ringer's, using heparin (10-20 UI/kg/h). We used Paired Filtration Dialysis Monitor in PE and LDL A; Citem 10 in IAPA. As plasma separator, we used a filter made of polypropylene, 0.2 m2 surface, 30 ml priming (Hemaplex BT 900). Hemolytic uremic syndrome was the most commonly treated disease (18/51 cases) with good results in 10/18 cases. We recorded, good results in vasculitis as well, in one girl with focal glomerulosclerosis in transplanted kidney and rapid improvement in all children with Guillaine-Barre Syndrome. PE treatment was effective in metabolic disorders such as tirosynemia and familiar hypercholesterolemia. Only 4/12 patients with acute liver failure due to viral hepatitis recovered. We had poor results in the remaining eight cases. Complications were rare and no viral infection was found in any patient. Our data show that it is possible to use these procedures in pediatric patients even though clinical indications and real effectiveness still need to be cleared up. PMID- 11197744 TI - Autotransfusion during extracorporeal membrane oxygenation. AB - To reduce allogeneic blood transfusion requirements during extracorporeal membrane oxygenation (ECMO) we evaluated an autotransfusion device which processes and retransfuses erythrocytes of changed ECMO-systems. We studied 10 elective changes of ECMO-systems in 7 patients. Hemoglobin levels, the amount of retransfused autologous blood and of transfused allogeneic packed red blood cell units were documented within 48 h after the system change and compared to the measurements obtained from former ECMO-system changes without using any autotransfusion device. We determined the Horrowitz-index, Interleukin 6, 10, TNF alpha and endothelin-I concentrations and coagulation parameters during the 48 hours after system change to study the compatibility of this procedure. Allogeneic blood transfusion was reduced from 7 to 2 units of packed red cells using the autotransfusion device. Additionally, no hints of any harmful side effects in these patients was observed. PMID- 11197745 TI - Regeneration of the junctional epithelium and connective tissue after transplantation of detergent-processed allo-teeth. AB - The authors have developed a new artificial dental implant and evaluated it in a dog model in terms of its potential to produce: I) regeneration of junctional epithelium; II) regeneration and attachment of connective tissue. The implants were constructed from allo-teeth. We removed the cell components from the periodontal ligaments of these teeth with a detergent (1% TritonX-100); the remaining acellular periodontal ligament acted as an extracellular matrix upon which regeneration and attachment could proceed. We placed 10 of these implants in the just-extracted sites of three beagle dogs. We observed regeneration of both junctional epithelium and connective tissue at all implant sites after 3 months. The connective tissue was attached in all cases. Use of the acellular periodontal ligament as an extracellular matrix may facilitate regeneration of host periodontal ligament tissue, thus contributing to recovery of host immunological defense and long-term oral function. PMID- 11197746 TI - Evidence for a nucleus accumbens CCK2 receptor regulation of rat ventral pallidal GABA levels: a dual probe microdialysis study. AB - We employed dual probe microdialysis in the nucleus accumbens and ipsilateral ventral pallidum of the halothane anaesthetized rat to investigate the effect of intra-accumbens perfusion with the sulphated octapeptide cholecystokinin (CCK-8S, 10-1000 nM, 60 min) alone and in the presence of the selective CCK1 and CCK2 receptor antagonists L-364,718 (10 and 100 nM) and PD134308 (10 nM), tetrodotoxin (TTX, 1000 nM) and the GABA(A) receptor antagonist bicuculline (1000 nM), on dialysate GABA levels in the ventral pallidum. Intra-accumbens perfusion with the 100 and 1000 nM concentration of CCK-8S was associated with a significant decrease (-16+/-3% and -23+/-3% vs basal, respectively) in ventral pallidum GABA levels. The CCK-8S (1000 nM) induced decrease in ventral pallidal dialysate GABA levels was abolished when PD134308, TTX and bicuculline, but not L-364,718, were included into the perfusion medium of the accumbens probe. The data indicate that nucleus accumbens CCK-8S exerts a CCK2 receptor mediated inhibition of ventral pallidal GABA levels. Furthermore, the TTX and bicuculline sensitivity of this effect suggests that this is possibly mediated via CCK2 receptors probably located on local GABA interneurons. PMID- 11197747 TI - The abundance of mRNAs for pyruvate dehydrogenase kinase isoenzymes in brain regions of young and aged rats. AB - The abundance of mRNAs for pyruvate dehydrogenase kinase (PDK) isoenzymes in four brain regions of young (10 wk) and aged (50 wk) rats was investigated by reverse transcription-polymerase chain reaction (RT-PCR). The mRNAs for PDK1, 2, and 4 were detected in all the regions examined. The level of PDK2 mRNA was the most abundant among the isoenzymes in all the brain regions when judged from the PCR cycles. The level of PDK1 mRNA was relatively high in cerebellum and cerebral cortex compared to medulla oblongata and hippocampus. Aging decreased the levels of mRNAs for PDK1 and 2 in cerebellum and increased the PDK2 mRNA in hippocampus and cerebral cortex. The level of PDK4 mRNA was not affected by aging. These results provide the first evidence suggesting that there is the regional difference in the abundance of mRNAs for PDK isoenzymes in rat brain and that the levels of mRNAs for the isoenzymes were affected by aging. PMID- 11197748 TI - Enhanced macrophage functions and cytokine production of lymphocytes after ingestion of bon narine in female BALB/c mice. AB - The purpose of this investigation was to determine the effects of bon narine treatment on macrophage and lymphocyte functions in mice. Twelve week-old female inbred BALB/c mice were given bon narine p.o. at 30 mg/kg per day and sacrificed after three months. Glucose consumption of peritoneal macrophages in the bon narine treated group during incubation up to 72 h was significantly higher than that in the control group. Activities of acid phosphatase (APH), beta glucuronidase (GLU) and lactate dehydrogenase (LDH) in the peritoneal macrophages in the bon narine treated group significantly increased compared to that in the control group. Macrophage production of nitric oxide stimulated by lipopolysaccharide (LPS) in the bon narine treated group was significantly increased. Interleukin-1beta (IL-1beta) production of peritoneal macrophages stimulated by LPS was significantly higher in the bon narine treated group. Stimulation indices in splenic lymphocytes by concanavalin A (Con A) in the bon narine treated group were significantly higher than that in the control group. Interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) production stimulated by Con A were significantly increased in the bon narine treated mice. Interleukin-4 (IL-4) production of splenic lymphocytes stimulated by Con A was not different in the control group and the bon narine treated group. These findings might suggest that oral administration of bon narine effectively enhanced the macrophage function and lymphocyte responsiveness in mice. PMID- 11197749 TI - N-ethylmaleimide inhibits xanthine oxidase activity with no detectable change in xanthine dehydrogenase activity in rabbit liver. AB - The effect of an alkylating agent, N-ethylmaleimide (NEM), on the activities of xanthine oxidase (XO) and xanthine dehydrogenase (XD) in the presence and absence of Cu2+ or trypsin in the cytosolic fraction from rabbit liver was examined. At concentrations ranging from 0.25 to 2.0 microM, allopurinol, which is generally considered to be a XO inhibitor, suppressed the XD activity (41.5-93.4% inhibition) in addition to the XO activity (28.6-88.4% inhibition) under basal conditions, without the addition of Cu2+ or trypsin. In contrast, NEM (100-400 microM) inhibited the XO activity (35.7-85.7% inhibition) without affecting the XD activity. Also, NEM inhibited the Cu2+- and trypsin-induced XO activities, but did not affect the XD activity at the same concentration range. These results demonstrate that NEM can be a selective inhibitor of XO activity in rabbit liver. PMID- 11197750 TI - Bile duct ligation promotes covalent drug-protein adduct formation in plasma but not in liver of rats given zomepirac. AB - Acyl glucuronides are reactive electrophilic metabolites of carboxylate drugs, capable of undergoing hydrolysis, rearrangement and covalent binding reactions with proteins in vivo. Such covalent drug-protein adducts may be prerequisites for certain idiosyncratic immune and toxic responses in susceptible individuals. The present study examined the effect of experimental cholestasis on the extent and pattern of formation of protein adducts in plasma and liver of rats given the non-steroidal antiinflammatory drug (NSAID) zomepirac (ZP). Groups of intact, bile-exteriorized and bile duct-ligated rats given a 50 mg/kg i.v. dose of ZP were studied for 24 hr. In intact rats, only 1.4% of the dose was recovered as the sum of ZP, ZP acyl glucuronide (ZAG) and its rearrangement isomers (iso-ZAG) in urine in 24 hr. In bile-exteriorized animals, 0.5% of the dose was recovered in urine in 24 hr, with 31.6% of the dose being recovered in bile (2.7% as ZP, 20.0% as ZAG and 8.9% as iso-ZAG). In the bile duct-ligated group, recovery of dose in 24 hr urine totalled 17.5% (1.7% as ZP, 6.7% as ZAG and 9.1% as iso-ZAG). ZAG and iso-ZAG were measurable in plasma only in the bile duct-ligated group, and covalent binding of ZP to plasma proteins was much higher (5-6 fold) than in intact or bile-exteriorized rats. Total adduct concentrations in liver were not significantly different among the three groups. Immunoblotting using a polyclonal ZP antiserum confirmed that serum albumin was a major target protein in plasma. The major ZP-modified bands in the livers of intact and bile-exteriorized rats were at about 110, 140 and 200 kDa. However, the bands at 110 and 140 kDa were much lower in the livers of bile duct-ligated rats. The results show that about 30% of ZP doses are normally excreted as ZAG and its isomers in bile, with only minor excretion in urine. Bile duct ligation shunts the glucuronide into blood (and urine), strongly promoting adduct formation with plasma proteins, and alters the pattern but not the total quantity of drug-modified proteins formed in the liver. PMID- 11197751 TI - Hepatocyte growth factor protects gastric epithelial cells against ceramide induced apoptosis through induction of cyclooxygenase-2. AB - Forced overexpression of cyclooxygenase-2 (COX-2) in intestinal cells has been shown to be associated with resistance to apoptosis. However, the role of physiologically-induced COX-2 in the regulation of apoptosis remains unclear. In the present study, we examined whether hepatocyte growth factor (HGF)-induced COX 2 affects ceramide-induced apoptosis in RGM-1 gastric epithelial cells. An externally applied cell permeable ceramide analogue, C2-ceramide, caused RGM-1 cell death in a dose-dependent manner, whereas an inactive ceramide analogue, C2 dihydroceramide, did not. TdT-mediated dUTP nick end labeling (TUNEL) assay showed that the C2-ceramide-induced cell death was apoptosis. Application of HGF rapidly induced the expression of COX-2, and HGF prevented the apoptotic cell death induced by C2-ceramide. However, the anti-apoptotic action of HGF was antagonized by coapplication of NS-398, a selective inhibitor of COX-2. Thus, these results indicate that COX-2 is involved in the survival signaling from HGF in gastric epithelial cells, and suggest a role for physiologically-induced COX-2 in the protection of the cells from apoptosis. PMID- 11197752 TI - A single neuron response to photodynamic effect of various aluminum and zinc phthalocyanines. AB - The photodynamic effects of sulphonated zinc and aluminum phthalocyanine derivatives as well as phosphonated aluminum phthalOcyanine on the firing of isolated crayfish mechanoreceptor neurons were studied. After 30 min staining neurons were irradiated with He-Ne laser (632.8 nm, 0.3 W/cm2) and changes in neuron firing frequency were recorded. Neuron firing was found to be very sensitive to photodynamic effect and could serve as a sensitive indicator of cell photodamage. It changed the firing level and then died at nanomolar concentrations of phthalocyanines. The dynamics of the neuron responses to photodynamic effects included stages of firing activation and/or inhibition prior to irreversible firing abolition. The order of these stages depended on photosensitizer type and concentration. The comparison of the dependencies of neuron lifetime on photosensitizer concentrations showed ZnPcS2 to be the most effective photosensitizer. PMID- 11197753 TI - Troglitazone has no effect on K(ATP) channel opener induced-relaxations in rat aorta and in human saphenous veins from patients with type 2 diabetes. AB - Troglitazone, a thiazolidinedione derivative, is an oral antidiabetic agent that enhances insulin sensitivity in insulin-resistant states. K(ATP) channels, on the other hand, have important roles protecting cardiovascular system in ischemic and/or hypoxic states. They are also important in the control of vascular tone, and therefore of blood pressure. We tested whether troglitazone can directly affect vascular K(ATP) channel opener-induced relaxations in vitro. 1, 10 or 100 microM troglitazone incubations for 30 min did not alter cromakalim (a K(ATP) channel opener)--induced relaxations in endothelium-denuded aortas from rat, saphenous veins from type 2 diabetic and nondiabetic patients. In addition, we compared the sensitivity to cromakalim in diabetic saphenous veins with that of nondiabetic veins. The concentration-response curve for cromakalim was shifted to the right in diabetic vein. pD2 values for cromakalim were 6.85+/-0.08 vs. 6.61+/ 0.04 (p<0.05) in nondiabetic (n:10) and diabetic (n:7) veins respectively. % maximum response of cromakalim was also significantly decreased by 24+/-3% in diabetic veins. However, responsiveness of veins to phenylephrine or sodium nitroprusside were similar in both groups. The results obtained may be clinically useful 1. suggesting that in ischaemic and/or hypoxic insults troglitazone may not worsen vascular dilatation, through K(ATP) channel, in diabetic patients who are more prone to these conditions than healthy people, 2. providing an evidence that diabetes causes an impaired dilatation of human saphenous vein through K(ATP) channels. This may partly be related with diabetes-induced vascular complications, such as vasospasm and even hypertension. Accordingly, since saphenous veins are used as conduit vessels in coronary by-pass graft surgery, the results also suggest that the defective dilatation through K(ATP) channels may play a role on the performance of saphenous vein grafts in type 2 diabetes. PMID- 11197754 TI - Gender differences of exploratory eye movements: a life span study. AB - Exploratory eye movements of normal subjects (39 male and 39 female) were recorded using an eye-mark recorder. Four parameters mean gazing time, total number of gazing points, mean scanning length, and total scanning length) were analyzed. Subjects were divided into three life spans as prepuberty (boys and girls), adult, and postpuberty. The mean gazing time of adult women was significantly longer than that of age-matched adult men, but not between men and women in prepuberty or postpuberty (postmenopausal older women and age-matched older men). The total number of gazing points of women was significantly smaller than that of men, but not significantly different between men and women in both prepuberty and postpuberty. Both the mean scanning length and total scanning length of adult women were shorter than those of age matched adult men, but no significant differences were found between men and women in both prepuberty and postpuberty. Furthermore, the mean gazing time of adult women was longer than that of men in prepuberty and postpuberty. The total scanning length of adult men was longer than that of women in both prepuberty and postpuberty. These findings suggest that gender differences of exploratory eye movements are observed only during the adult phase, which indicates that visual information processing may be regulated by gonadal hormones in humans. PMID- 11197755 TI - Contribution of diet to the dosing time-dependent change of vitamin D3-induced hypercalcemia in rats. AB - We have recently reported that the degree of hypercalcemia as an adverse effect induced by a single large-dose of active vitamin D3 varied with its dosing time without alteration in therapeutic effect for secondary hyperparathyroidism in patients with chronic renal failure. The present study was conducted to elucidate an effect of intestinal calcium (Ca) absorption on the chronopharmacological profiles of vitamin D3. 1, 25-dihydroxy-cholecalciferol (D3, 2 microg/kg) or vehicle alone was orally administered at two different times (2 and 14 hours after lights on; HALO) to male Wistar rats (n= 10) kept in rooms with a 12 h light-dark cycle. Blood samples for serum Ca concentration were taken before and 3, 6, 9, and 12 hours after the administration. Urine was collected for 6 hours after dosing. An identical protocol was repeated using the same animals after 16 hours fasting by a cross-over fashion. Under free-fed condition, basal concentration of serum Ca was higher at a resting period (lights on) than during an active period (lights off). Serum Ca reached its peak at 6 hours after dosing in both timings, while the value was significantly higher in the 2 HALO trial than in the 14 HALO trial. Area under the serum Ca concentration-time curve from 0 to 12 hours (AUC0-12h) and urinary excretion of Ca for 6 hours were also significantly higher in the 2 HALO trial than in the 14 HALO trial. When fasted, basal Ca concentration was reduced compared with the free-fed condition, while the daily variation was maintained. Serum Ca concentration profiles from 3 to 12 hours after dosing were not significantly different between the 2 HALO and 14 HALO trials. The AUC0-12h of serum Ca or its urinary excretion was not different between both trials. Serum concentrations of parathyroid hormone and total protein, measured before and 6 hours after the dosing were not affected by the dosing schedule. We have concluded that intestinal Ca absorption is a major factor for the chronopharmacological phenomenon of D3-induced hypercalcemia in intact rats, while intestinal and renal involvement may be relatively small in the mechanism of the intrinsic diurnal variation of serum Ca. PMID- 11197756 TI - Immediate effects of the serotonin antagonist granisetron on temporomandibular joint pain in patients with systemic inflammatory disorders. AB - The aim of this study was to investigate if the 5-HT3 antagonist granisetron reduces temporomandibular joint (TMJ) pain in patients with systemic inflammatory joint disorders. Sixteen patients with systemic inflammatory joint disease with pain localized over the TMJ region and tenderness to digital palpation of the TMJ were included. The current resting pain (VASRest) and the pain during maximum mouth opening (VAS(MVM)) of the TMJs were assessed with a 100 mm visual analogue scale. An electronic pressure algometer was used to estimate the pressure pain threshold (PPT) over the lateral aspect of the TMJ. Venous blood was collected for measurement of the plasma and serum levels of 5-HT, erythrocyte sedimentation rate, rheumatoid factor and C-reactive protein. The selective 5-HT3 receptor antagonist granisetron or saline were injected into the posterior part of the upper TMJ compartment in a randomized double-blind manner. The patients in the granisetron group had lower VASRest than the patients in the saline group after 10 min. In the granisetron group, VASRest was decreased after 10 min, while VAS(MVM) was decreased and PPT increased after 20 min. In the saline group, VAS(MVM) was decreased after 20 min. In conclusion, granisetron has an immediate, short-lasting and specific pain reducing effect in TMJ inflammatory arthritis. The 5-HT3 receptor may therefore be involved in the mediation of TMJ pain in systemic inflammatory joint disorders. PMID- 11197757 TI - Characterization of three genes encoding enzymes of the folate biosynthetic pathway in Plasmodium falciparum. AB - Although the folate metabolic pathway in malaria parasites is a major chemotherapeutic target, resistance to currently available antifolate drugs is an increasing problem. This pathway, however, includes a number of enzymes that, to date, have not been characterized despite their potential for clinical exploitation. As a step towards evaluation of additional targets in this pathway, we report the isolation and characterization of 3 new genes that encode homologues of GTP cyclohydrolase I (GTP-CH), dihydrofolate synthase/folylpolyglutamate synthase (DHFS/FPGS) and serine hydroxymethyltransferase (SHMT). The genes encoding GTP-CH and SHMT are unambiguously assigned to chromosome 12, while that for DHFS/FPGS is tentatively assigned to chromosome 13. All 3 genes are expressed in blood-stage parasites, yielding transcripts of which only ca 60-70% is accounted for by coding sequence. All 3 of the proteins predicted to be encoded by these genes display sequence differences compared to the human host homologues that may be of functional significance. These data bring the complement of cloned genes that encode activities in the pathway to seven, leaving only the gene encoding dihydroneopterin aldolase (DHNA) to be identified in the route from GTP to folate synthesis and folate turnover in the thymidylate cycle. PMID- 11197758 TI - The effect of anthelmintic treatment on helminth infection and anaemia. AB - A 24-week randomized double blind intervention trial was conducted on adult female tea pluckers from an estate in Bangladesh to investigate the impact of iron supplementation and anthelmintic treatment on changes in ferritin and haemoglobin levels as well as on prevalence and intensity of helminth infections. A total of 553 women were randomly assigned to 1 of 4 intervention groups: group 1 received iron supplementation on a weekly basis, group 2 received anthelmintic treatment at the beginning and half way through the trial, group 3 received both iron supplementation as group 1 and anthelmintic treatment as group 2, and group 4 was a control group and received placebos for both iron supplementation and anthelmintic treatment. Prevalence and intensity of helminth infections (egg counts/g stool) of Ascaris lumbricoides, Trichuris trichiura and hookworms significantly fell in the 2 groups receiving anthelmintic treatment and there were some reductions in the 2 groups not receiving anthelminthic treatment. Haemoglobin and haematocrit concentrations increased significantly in the iron supplemented groups with smaller increases in the anthelmintic only group. All women showed a decrease in serum ferritin levels post-trial with greater losses in the 2 dewormed groups. Significant negative associations were found between hookworm egg counts and ferritin levels and Trichuris trichiura egg counts and haemoglobin concentration. PMID- 11197759 TI - Cuticle heterogeneity as exhibited by Pasteuria spore attachment is not linked to the phylogeny of parthenogenetic root-knot nematodes (Meloidogyne spp.). AB - The cuticle is a major barrier prohibiting the infection of nematodes against micro-organisms. The attachment of bacterial spores of the nematode hyperparasite Pasteuria penetrans (PP1) to field populations of root-knot nematodes (RKN, Meloidogyne spp.) from Burkino Faso, Ecuador, Greece, Malawi, Senegal and Trinidad and Tobago were assayed in standard attachment tests. The attachment of spore population PP1 to different field populations of root-knot nematode showed that the rates of attachment differed between countries. Similar tests were also undertaken on P. penetrans spores from these countries against 2 species of RKN, M. incognita and M. arenaria. The results showed a high degree of variability in spore attachment with no clear distinction between the 2 species of nematode. It has been hypothesized that Pasteuria spore attachment is linked to nematode species designations and this study clearly shows that this is not the case. Further tests showed that variation in spore attachment was not linked to nematode phylogeny. The results therefore beg the question of how do parthenogenetic root-knot nematodes maintain cuticle variability in the face of such an aggressive hyperparasite. PMID- 11197760 TI - Membrane localization and demonstration of isoforms of nucleoside triphosphate hydrolase from Toxoplasma gondii. AB - Toxoplasma gondii has a unique enzyme, a NTPase, which has a wide specificity toward NTP. In the present study, we produced a monoclonal antibody (IgG1, 6C6) against the enzyme which could recognize NTPase isozymes among several strains of T. gondii. Three avirulent strains of T. gondii, ME49, Beverley and Nakayama, were found to have 1 NTPase (63 kDa, pI 6.0), while a virulent strain RH and an avirulent strain Fukaya had 2 isozymes (63 kDa) with different pIs (pIs 6.0 and 6.5 for the former, and pIs 6.2 and 6.4 for the latter, respectively), suggesting that this monoclonal antibody recognizes a common epitope of NTPase among T. gondii strains. Furthermore, 6C6 could inhibit NTPase activity in the presence of dithiothreitol in a dose-dependent manner, and immuno-EM study of NTPase revealed that this molecule is located on the surface membrane of T. gondii tachyzoites. When Vero cells were co-cultured with tachyzoites pre-treated with 6C6, the number of infected cells significantly decreased, suggesting that 6C6 inhibits invasion of the parasites to host cells. These data suggest that the molecule recognized by 6C6 might be considered a potential candidate antigen for vaccines against T. gondii tachyzoites. PMID- 11197761 TI - Gp63 gene polymorphism and population structure of Leishmania donovani complex: influence of the host selection pressure? AB - The gp63 encoding genes were characterized by PCR-RFLP in 35 isolates representative of the Leishmania donovani complex (L. infantum, L. donovani, L. archibaldi and L. chagasi), with special attention to Mediterranean L. infantum from different geographical origins, and in separate groups from Old World Leishmania (L. major, L. tropica and L. aethiopica). The aim was to evaluate how the possible selective pressure by the host on these important surface proteins would influence structuring of our sample. Comparison was carried out with the structure obtained (i) from reported isoenzyme data, characters supposed to vary neutrally, and (ii) from PCR-RFLP analysis of gp63 inter-genic regions, containing nontranslated spacers and regulatory genes. Polymorphism within the gp63-encoding region, was much higher than in gp63 inter-genic regions. In the gp63 intra-genic dendrogram, the 4 species of L. donovani complex were discriminated and quite distinct from outgroups. Within L. infantum, geographical structuring was observed and did not overlap with the structure built-up from isoenzymes and inter-genic data. These results support the idea of a strong host selection on gp63, at vector level but most of all at vertebrate (human or dog) immunological level. Furthermore, they illustrate how the nature of genetic characters may influence the perception of population structuring. PMID- 11197762 TI - Species-specific antigens in salivary glands of phlebotomine sandflies. AB - Saliva inoculated by sandfly females during feeding stimulated production of high levels of anti-saliva antibodies. To determine whether 3 species of the genus Phlebotomus have species-specific salivary antigens we performed dot-blots and immunoblots using sera from mice, hamsters and rabbits repeatedly bitten by sandflies. Important differences were found in the antigen components of the salivary gland lysates (SGL) of Phlebotomus papatasi, P. perniciosus and P. halepensis. In total 4-9 species-specific antigens were detected in each species by immunoblotting. Cross-reactivity was not detected between P. papatasi and the other species tested; in the SGL of P. papatasi sera from animals bitten by this species recognized 5-7 major antigens while sera from animals bitten by other species did not react. A weak cross-reaction was observed between P. perniciosus and P. halepensis; in SGL from P. perliciosus, the sera from rabbits and hamsters bitten by this species recognized about 8 intense bands while sera from animals bitten by P. halepensis reacted weakly with up to 4 saliva polypeptides. PMID- 11197763 TI - Factors affecting the component community structure of haemoparasites in bank voles (Clethrionomys glareolus) from the Mazury Lake District region of Poland. AB - The prevalence and abundance of infections with haemoparasites were studied over a 3 year period in Clethrionomys glareolus (bank vole, n = 420) sampled from forests in the NE of Poland. Total species richness was 5 (Prevalence = Haemobartonella sp. 63.1%, Bartonella grahamii 27.4%, Hepatozoon erhardovae 31.4%, Trypanosoma evotomys 15% and Babesia microti 1.0%) with 81.9% of the voles carrying at least 1 species and a mean infracommunity species richness of 1.4. Variation in species richness was determined primarily by season and year, and the interaction of these factors. The observed frequency distribution of infracommunity species richness did not differ from that predicted by a null model, suggesting that there were no marked associations between the species. Analyses of prevalence and abundance of infection with each species in turn, revealed that overall the principal causes of variation were temporal and seasonal and their interaction, intrinsic factors such as age and sex playing only a minor role. However, the relative importance of specific extrinsic, and rarely intrinsic, factors varied and was distinct for each of the species in the study. Prevalence data revealed 4 sets of 2-way associations between species, mostly varyingly dependent on combinations of intrinsic and extrinsic factors. Analysis of quantitative associations suggested 4 sets of positive 2-way interactions, 3 of which remained after controlling for the effect of extrinsic and intrinsic factors on the abundance of each species, but only one could be unequivocally accepted (Haemobartonella sp. +B. grahamii) after correction for multiple comparisons. These data are discussed in the context of the changing ecological profiles in this region of Eastern Europe and, in a wider context, in relation to current understanding of the factors which shape component community structures of haemoparasites in wild rodents. PMID- 11197764 TI - Myxosporidia and macrophage centres in chub (Leuciscus cephalus)--quantitative interactions focus on Myxobolus cyprini. AB - Six myxosporidian species were found in chub (Leuciscus cephalus) originating from Lower Austrian rivers. The frequency of the parasites and their localization was recorded. In all chub, independent of size and origin, Myxobolus cyprini occurred predominantly in the macrophage centres (MCs) of the haematopoietic organs, spleen and kidney. Exclusively in the head kidney of young fish not yet described vermicular plasmodia containing spores of M. cyprini were found. In muscle tissue the prevalence of M. cyprini was comparatively low. Other species of Myxobolus characterized by plasmodial cysts frequently occurred in gills and swimbladder but were rarely detected, and only in small numbers, in the haematopoietic organs. The number of M. cyprini spores and the relative volume of MCs in the haematopoietic organs were estimated in order to examine possible correlations. Significant interrelated changes were found only in juvenile fish up to a size of 15 cm. In bigger fish, the number and size of macrophage aggregates were highly variable and independent of infection intensity and fish size, but the number of spores never exceeded that of the aggregated macrophages. The data suggest that due to an early date of infection M. cyprini is the only species which is closely associated with macrophage aggregation. PMID- 11197765 TI - Praziquantel-induced tegumental damage in vitro is diminished in schistosomes derived from praziquantel-resistant infections. AB - The aggressive use of praziquantel to combat schistosomiasis in Egpyt raises concern about the possible emergence of resistance. Eggs from Egyptian patients with praziquantel-resistant infections (not cured by 3 doses of praziquantel) have been used to establish infection-specific schistosome isolates in mice. The response of these worms to the drug was observed in vitro, in order to determine if the isolates obtained from these resistant infections were, in fact, less responsive to praziquantel. One of the hallmark effects of praziquantel on schistosomes in vitro is a disruption of the worm's outer surface, the tegument. Here, praziquantel-induced tegumental damage is observed in 3 distinct isolates, 2 derived from resistant infections and 1 from an infection cured by a single dose. The isolates from the resistant infections were less susceptible to praziquantel-induced tegumental damage in vitro, suggesting that the worms are in some way less responsive to the drug. PMID- 11197766 TI - The Schistosoma mansoni host-interactive tegument forms from vesicle eruptions of a cyton network. AB - During trans-dermal invasion of the vertebrate host, larval schistosomes (cercariae) transform into schistosomula and become enveloped by a double lipid bilayered, tegumental membrane. The glucose transporter protein SGTP4 is found exclusively in these host-interactive tegumental membranes and in membranous vesicles proposed to be their precursor. In this study, we monitored the appearance and migration of this tegumental marker protein during larval transformation to test the current model of tegumental membrane biosynthesis in parasitic blood flukes. Only minutes after transformation was initiated, SGTP4 began accumulating in a previously unrecognized, bilaterally symmetrical, 'cyton network' beneath the peripheral muscle. Approximately 30 min after the initiation of transformation the marker protein was seen in tubules connecting the network to the surface and erupting onto the surface in discrete patches. After I h the patches were regularly arrayed over the schistosomula body and began to cover the anterior organ. By 3 h the staining has largely resolved into a contiguous layer of fluorescence covering most of the worm surface. These findings confirm earlier suggestions, based on electron microscopy, that the parasite's surface tegumental membranes are derived from the migration of membranous vesicles produced within cytons and reveal a new subtegumental architecture interconnecting the cytons. PMID- 11197767 TI - Toxicity of cadmium and zinc to encystment and in vitro excystment of Parorchis acanthus (Digenea: Philophthalmidae). AB - The toxicity of cadmium, zinc and cadmium/zinc mixtures at concentrations ranging from 1000 to 50000 microg/l were investigated against cercariae and metacercariae of Parorchis acanthus obtained from the dog whelk Nucella lapillus. Cercarial encystment at concentrations of 25000 microg/l or higher was significantly impaired by all test metals; however, at lower concentrations only zinc demonstrated toxicity. Mixtures of cadmium and zinc had a synergistic effect compared with single metal toxicity but only at 50000 microg/l. Excystment in vitro was only significantly affected by cercariae exposed to cadmium/zinc mixtures whilst encysting. Twenty-four h exposures of fully formed cysts had no effect on excystment in vitro. Effects on in vitro excystment rates over a 2 h period demonstrated widespread effects for cercariae-exposed P. acanthus. No effects were evident on excystment rates of cyst-exposed parasites. PMID- 11197768 TI - Toxicity of cadmium and zinc to miracidia of Schistosoma mansoni. AB - The specific objectives of this study were to elucidate metal toxicity to hatching, survival and avoidance behaviour of Schistosoma mansoni miracidia. The toxicity of cadmium, zinc, and cadmium/zinc mixtures at concentrations ranging from 10000 to 10 microg/l was investigated. Metal mixture toxicity investigation was undertaken with equal concentrations of the metals. The hatching of miracidia from eggs was inhibited by concentrations of 1000-10000 microg/l of single metals. Metal mixtures had no effect on egg hatching. Survival of miracidia was reduced by increasing metal concentration except at concentrations of 10 microg/l for single metal toxicity where survival was increased above the control. Miracidia demonstrated a rapid avoidance behaviour when briefly exposed to heavy metals. The mechanisms of metal toxicity to miracidia are briefly discussed. PMID- 11197769 TI - Distribution of nitric oxide synthase immunoreactivity in the nervous system and peripheral tissues of Schistosoma mansoni. AB - The distribution of nitric oxide synthase (NOS) immunoreactivity and putative NOS activity in adult Schistosoma mansoni was analysed using 3 different types of NOS antibodies and NADPH-diaphorase histochemistry. Although potential involvement of the gaseous radical nitric oxide (NO) in host response to infection by schistosomes has been suggested, there is little or no information available regarding the role, or even the presence, of the NO pathway in schistosomes themselves. Here, we demonstrate that antibodies against neuronal NOS (nNOS) and inducible NOS (iNOS) isoforms stain adult worms with distinctive patterns; anti endothelial NOS (eNOS) shows no selective labelling. nNOS-like immunoreactivity is found in the main nerve cords and the peripheral nervous system. Putative sensory neurons with apical neuronal processes leading to the tegument of male worms are also immunoreactive for nNOS. Anti-iNOS labels a variety of predominantly non-neuronal tissues, showing intense labelling at or near the surface of the worm and in components of the gastrointestinal tract. The distribution of NADPH-diaphorase reactivity (a histochemical marker of NOS), is generally similar to the pattern of NOS immunoreactivity, including labelling of neuronal-like cells as well as developing eggs. These results suggest that an NOS like enzyme is present in S. mansoni, and indicate potential roles for the different NOS isoforms in neuronal signalling, reproduction and development. PMID- 11197770 TI - A phylogenetic analysis of filarial nematodes: comparison with the phylogeny of Wolbachia endosymbionts. AB - Infection with the endosymbiotic bacteria Wolbachia is widespread in filarial nematodes. Previous studies have suggested concordance between the phylogeny of Wolbachia with that of their nematode hosts. However, there is only one published molecular phylogenetic study of filarial species, based on the 5S rRNA gene spacer. The phylogeny proposed by this study is partially incongruent with previous classifications of filarial nematodes, based on morphological characters. Furthermore, both traditional classifications and molecular phylogenies are, in part, inconsistent with the phylogeny of Wolbachia. Here we report mitochondrial cytochrome oxidase I (COI) gene sequences for 11 species of filaria and for another spirurid nematode which was included as an outgroup. In addition, 16S rRNA, wsp and ftsZ gene sequences were generated for the Wolbachia of several filarial species, in order to complete the available data sets and further resolve the phylogeny of Wolbachia in nematodes. We used these data to evaluate whether nematode and Wolbachia phylogenies are concordant. Some of the possible phylogenetic reconstructions based on COI gene were congruent with the phylogeny of Wolbachia and supported the grouping of the rodent filaria Litomosoides sigmodontis with the lymphatic filariae (i.e. Brugia spp. and Wuchereria spp.) and the sister group relationship of Dirofilaria spp. and Onchocerca spp. However, the placement of the Wolbachia-free filaria Acanthocheilonema viteae is ambiguous and dependent on the phylogenetic methods used. PMID- 11197771 TI - [An approach to early genetic alterations in precancerous cells]. AB - To investigate the potential role of the PTEN tumor-suppressor gene in the carcinogenesis of ovarian endometrioid carcinoma and its related subtype, clear cell carcinoma, we examined 20 ovarian endometrioid carcinomas, 24 clear cell carcinomas and 34 solitary endometrial cysts of the ovary for LOH at 10q23.3 and point mutations of the PTEN gene, using a laser-assisted microdissection method. LOH was found in 8 of 19 ovarian endometrioid carcinomas (42.1%), 6 of 22 clear cell carcinomas (27.3%) and 13 of 23 solitary endometrial cysts (56.5%). Somatic mutations in the PTEN gene were identified in 4 of 20 ovarian endometrioid carcinomas (20.0%), 2 of 24 clear cell carcinomas (8.3%) and 7 of 34 solitary endometrial cysts (20.6%). In 5 endometrioid carcinomas with endometriosis, 3 displayed LOH events common to both the carcinoma and the endometriosis. In 7 clear cell carcinomas with endometriosis, 3 displayed LOH events common to both the carcinoma and the endometriosis. In no cases there were LOH events in the endometriosis only. These results indicate that inactivation of the PTEN gene is an early event in the development of both endometrioid and clear cell carcinoma of the ovary. A laser-assisted microdissection method enables us to collect target cells without contamination by non-tumor cells. We expect that this technique will be very useful for investigating genetic alterations in cancerous or precancerous lesions. Early genetic alterations in various precancerous cells detected by light microscopy can be readily identified by the tissue microdissection method. PMID- 11197772 TI - [Comparative genomic hybridization for analysis of chromosomal changes in cisplatin-resistant ovarian cancer]. AB - In our attempt to find characteristic genetic changes in resistant tumors, we screened the whole genome for gene aberrations in 28 primary ovarian cancers, using the comparative genomic hybridization (CGH) method. These cancers included 14 tumors from patients who did not respond to cisplatin-based combination chemotherapy in comparison with 14 tumors from patients who completely responded to the chemotherapy. We found gains in chromosomal region 1q21-q22 and 13q12-q14 to be related to the drug-resistant phenotype in ovarian cancer patients. Several genes encoding transcription factors, oncogenes, cell cycle regulators and regulators of the apoptotic pathway are found to be located on these regions of the chromosomes, and these genes are potential modulators for toxic insults in cancer cells. This is the first report that shows the relationship between certain genomic aberrations and clinical resistance for cisplatin-based chemotherapy in ovarian cancer patients based on the CGH analysis. Present findings suggest that these chromosomal gains may be potential indicators for prediction of resistance in ovarian cancer patients prior to cisplatin-based chemotherapy. PMID- 11197773 TI - Immunohistochemical estimation of in-situ cell cycle time in neoplastic epithelial cells in human large intestine: a new cell proliferation index. AB - In-situ cell cycle time (in-situ Tc) of epithelial cells could be estimated by using a formula; in-situ Tc = cell proliferation rate divided by mitosis rate, on a scale of Tm (cell cycle time in M phase) arbitrary unit (AU), In order to see the nature of in-situ Tc in the adenoma-carcinoma sequence in the human large intestine, the in-situ Tc in 27 cases of adenoma and 71 cases of adenocarcinoma with adenoma components in the human large intestine was estimated by using this formula, counting proliferating cells and mitotic cells in the immunohistochemistry of Ki-67 antigen. C12 antigen was examined as an oncogenic progression indicator in the adenoma-carcinoma sequence. The in-situ Tc tended to shorten in adenoma in accordance with the histological grading of atypia but not in adenoma component. No significant differences in the in-situ Tc was recognized as a whole among adenomas, adenoma components and adenocarcinomas in the mucosa, whereas the in-situ Tc of adenoma components with moderate to severe atypia was significantly longer than that of adenocarcinomas in the mucosa (p = 0.05). The in-situ Tc lengthened in adenocarcinomas invading the submucosa and shortened in adenocarcinomas invading the proper muscular layer. The cases expressing the C12 antigen increased in order of adenoma, adenoma component and adenocarcinoma. The cases expressing the C12 antigen indicated short in situ Tc in the adenomas and adenocarcinomas but not in the adenoma components. Thus, the estimated in-situ Tc is a useful index of the oncogenetic progression, which is different from that detected by the C12 antigen. PMID- 11197774 TI - Direct effect of danazol on endometrial hyperplasia in adenomyotic women: treatment with danazol containing intrauterine device. AB - It is well known that danazol has a direct effect on endometriosis tissue and cell. We have been treating adenomyotic women with danazol containing intrauterine device (D-IUD) from June 1993 to August 2000 and significant decrease of dysmenorrhea and serum CA-125 levels were observed. Of fifty-nine adenomyotic women, eight women were also diagnosed by endometrial biopsy as endometrial hyperplasia and one woman was diagnosed as atypical endometrial hyperplasia. In these endometrial hyperplastic patients, endometrial tissues were obtained before insertion and at the time of removal or exchange of D-IUD and examined pathologically. In all of the 9 women, histopathological findings of endometrial hyperplasia disappeared after D-IUD treatment. In particular, in one patient, findings of atypical endometrial hyperplasia also disappeared after D IUD treatment. She is now closely observed at our clinic using D-IUD. By these evidences, we postulate that D-IUD is one of the treatment choices of endometrial hyperplasia given exposure of the endometrium to such an extraordinary high concentration of danazol released by D-IUD and avoidance of adverse effects of oral danazol or general administration of GnRH and progesterone. In particular, in atypical endometrial hyperplasia case, its mechanisms might give great benefit to patient. However, mechanisms of direct effect of danazol on endometrial hyperplasia remain to be elucidated in the future study. PMID- 11197775 TI - Genome-wide profiling of gene amplification and deletion in cancer. AB - Accumulations of genetic changes in somatic cells induce phenotypic transformations leading to cancer. Among these genetic changes, gene amplification and deletion are most frequently observed in several kinds of cancers. Amplification of oncogene and/or deletion of tumor suppressor gene, together with dysfunction of the gene by point mutation, are the main causes of cancer. Genome-wide analysis of amplification and deletion of genes in cancers is basic to resolving the mechanisms of carcinogenesis. Comparative genomic hybridization (CGH) developed in 1992 has been utilized to identify DNA copy number abnormalities in various kind of cancers and several reports have shown its usefulness in screening of the genes involved in carcinogenesis, and also in the identification of prognostic factors in cancer. We have shown that 1q23 gain is associated with neuroblastomas that are resistant to aggressive treatment, and have poor prognosis, and 1q and 13q gains are possibly related to drug resistance in ovarian cancers. Recently, the "rough draft" of the human genome was reported and we are ready to utilize the vast information on genomic sequences in cancer research. Moreover, microarray technology enables us to analyze more than ten thousand genes at a time and revealed genetic abnormalities in cancers at a genome-wide level. By combination of microarray and CGH, a powerful screening method for oncogenes and tumor suppressor genes in cancers, called array-CGH, has been developed by several groups. In this article, we overview these genome-wide analytical methods, CGH and array-CGH, and discuss their potential in molecular characterization of cancers. PMID- 11197776 TI - Gastrointestinal tumorigenesis in Smad4 (Dpc4) mutant mice. AB - The SMAD4 (Dpc4) gene plays a key role in the TGF-beta signaling pathway. We recently inactivated the mouse homolog Smad4. The homozygous mutants were embryonic lethals, whereas the heterozygotes were viable and fertile. Although young heterozygotes were normal, old mice developed gastric and duodenal polyps similar to those found in human juvenile polyps characterized by abundant stroma and eosinophilic infiltrations. These data are consistent with the reports that a subset of human juvenile polyposis kindreds carry germline mutations in the SMAD4 gene. We then introduced the Smad4 mutation into the Apc delta 716 knockout mice, a model for human familial adenomatous polyposis. Because both Apc and Smad4 are located on mouse chromosome 18, we constructed by meiotic recombination, compound heterozygotes carrying both mutations on the same chromosome. In such mice, intestinal polyps developed into more malignant tumors than those in the simple Apc delta 716 heterozygotes, showing an extensive stromal cell proliferation and strong submucosal invasion. These results indicate that mutations in SMAD4 play a significant role in the malignant progression of colorectal tumors. PMID- 11197777 TI - [Transforming growth factor-beta signaling and cancer]. AB - Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that inhibits the growth of most types of cells and induces fibrosis of various tissues. TGF-beta binds to two different types of serine/threonine kinase receptors, and activate Smad proteins. Perturbation of the TGF-beta signaling pathway results in tumorigenesis of various tissues. TGF-beta/Smad signaling is regulated by several regulatory proteins, including inhibitory Smads and transcriptional corepressors. Abnormalities in these negative regulators of TGF beta signaling may also involved in tumorigenesis of certain tissues. PMID- 11197778 TI - Antibiotic therapy of enteric fever. PMID- 11197779 TI - Potential mechanisms of hypothyroidism-induced hyponatremia. PMID- 11197780 TI - KL-6 as a serum marker for amiodarone-induced pulmonary toxicity. PMID- 11197781 TI - Parkinsonism in a patient with AIDS. PMID- 11197782 TI - Re-analysis of clinical features of 89 patients with autoimmune hepatitis using the revised scoring system proposed by the International Autoimmune Hepatitis Group. AB - OBJECTIVE: The diagnostic criteria of autoimmune hepatitis (AIH) were recently modified by the International Autoimmune Hepatitis Group. This study was performed to assess the impact of the revised scoring system on the diagnosis of AIH. PATIENTS AND METHODS: We re-analyzed the clinical features of 89 patients diagnosed as AIH in Nagasaki Prefecture, Japan, using the revised scoring system, and compared the scores and final diagnosis with our previously published results using the original system. RESULTS: Of the 89 patients with AIH, 40 (45%) were classified using the new system as "definite" AIH, 41 (46%) as "probable" AIH, and 8 (9%) patients were categorized as "others". Of these, 37 (42%), 35 (39%), and 4 (4%) patients who were classified as "definite", "probable", and "others" by the original system remained in the same category by the revised system, respectively. However, 3, 4, and 6 patients were re-categorized as "definite" from "probable", "others" from "probable", and "probable" from "definite", respectively. The difference in aggregate scores between the above two systems ranged from -5 to +2. The main contributing factors to the changes in aggregate AIH score were "other autoimmune disease(s)" and "interface hepatitis without lobular involvement and bridging necrosis on liver histology". However, the main contributing factors to the demotions from "definite" to "probable" and form "probable" to "others" were those related to the characteristics of biliary diseases, i.e., antimitochondrial antibody positive, biliary changes in liver histology, and alkaline phosphatase: aspartate aminotransferase ratio between 1.5 and 3.0. Moreover, two patients who had no histological evidence of AIH were both re-categorized as "others" from "probable" AIH. CONCLUSION: Our results indicated that the diagnosis, whether based on the revised or original system, was the same in the majority of AIH patients, but the revised scoring system excluded cases who had features suggestive of biliary diseases from "definite" AIH, and also confirmed that a diagnosis of "definite" AIH should not be made without liver histology. PMID- 11197783 TI - Depressor effect by exercise training is associated with amelioration of hyperinsulinemia and sympathetic overactivity. AB - OBJECTIVE: In hypertensive subjects, exercise training is a therapeutic modality that not only lowers blood pressure but also corrects metabolic abnormality, such as hyperinsulinemia. Insulin causes sympatho-excitation via the modification of baroreflex, norepinephrine release, or central sympathetic outflow. However, the link between neural and metabolic changes by exercise training in hypertensive patients remains unknown. The aim of this study was to examine whether or not the blood pressure lowering effect of exercise training is associated with the improvement of insulin sensitivity in conjunction with the inhibition of sympathetic tone in hypertensive patients. METHODS: We evaluated plasma insulin levels, arterial baroreflex function and humoral parameters before and after exercise training. Twenty-nine patients with essential hypertension under hospitalization participated in the study. Before and after three weeks of exercise training (75% max VO2, 6 min, q.i.d.), 24-hour blood pressure recordings, arterial baroreflex function testing and 75 g glucose tolerance tests were conducted. Area under the curve of insulin (sigma insulin) to glucose load was calculated as an index of hyperinsulinemia. RESULTS: Three weeks of exercise training decreased the 24-hour mean arterial pressure, heart rate and sigma insulin, and improved barorefiex function. There was a significant correlation between the reduction of arterial pressure and the change in sigma insulin. Furthermore, the reduction of sigma insulin was correlated with the improvement of baroreflex function and with the decrease in heart rate. CONCLUSIONS: Exercise training lowered the arterial pressure, with parallel changes in heart rate, baroreflex function and insulin resistance. The correction of sympathetic overactivity was closely associated with the amelioration of hyperinsulinemia. Our results suggest that the improvement of neuro-metabolic factors may be involved in the depressor effect caused by exercise training. PMID- 11197784 TI - Intermittent nitrate therapy for prior myocardial infaraction does not induce rebound angina nor reduce cardiac events. AB - OBJECTIVE: Long-term nitrate therapy for ischemic heart disease may cause drug tolerance which diminishes its beneficial effects; consequently, intermittent administration of nitrates is recommended. With this regimen, however, the potential occurrence of rebound angina during the nitrate-free intervals is a source of concern. SUBJECTS AND METHODS: We carried out a retrospective study of 606 patients to determine whether rebound angina occurred when conventional continuous nitrate administration was replaced by intermittent administration as part of a long-term therapy protocol for prior myocardial infarction. The subjects were receiving treatment for myocardial infarction and included 293 patients treated with nitrates (Nitrate group) and 313 patients who were not (No nitrate group). The former included 186 patients who received intermittent nitrate administration (Intermittent group) and 107 patients who received continuous administration (Continuous group). The mean period of observation was 4.3 +/- 1.6 months. RESULTS: There were no cases of rebound angina in the Intermittent group. Cardiac events occurred in one case in the No-nitrate group (0.3%), in 4 cases in the Continuous group (3.7%) and in 2 cases in the Intermittent group (1.1%). The incidence of cardiac events was thus significantly increased in the Continuous group compared to the No-nitrate group (p < 0.05; odds ratio 9.06; 95% CI 1.41-58.28). The Intermittent group did not significantly differ from the No-nitrate group in the incidence of cardiac events. CONCLUSION: It is concluded that intermittent administration of nitrates does not cause rebound angina and is therefore safe. A randomized controlled trial is needed to find the long-term effect on cardiac events. PMID- 11197785 TI - Efficacy of anti-anginal drugs in the treatment of angina pectoris associated with silent myocardial ischemia: importance of quantitative Holter ECG data for patient activity. AB - METHODS: We evaluated the clinical efficacy of transdermal nitroglycerin (NTG TTS), a patch application of a nitrate, in the treatment of 27 patients with angina pectoris who had asymptomatic myocardial ischemic (SMI) attacks, using a double-blind cross-over method. Evaluation was made using Holter ECG and patient activity data. RESULTS: In frequency and duration of continuation of SMI episodes, no significant differences were noted between the observation and placebo treatment periods, while the values of both these parameters were decreased significantly in the active drug treatment period compared with those in the observation and placebo treatment periods. Critical heart rate, the heart rate at the initiation of ST-segment depression, was significantly higher during the period of active drug treatment than during the placebo treatment and observation periods. In SMI frequency index, which was determined by adjusting the SMI frequency for the number of steps taken, there were no significant differences between the 3 periods. The SMI time index was significantly lower in the active drug treatment period than in the observation period. CONCLUSIONS: These results indicated that the clinical evaluation of the efficacy of anti anginal drugs against SMI should take into consideration individual patient activity data. PMID- 11197786 TI - Clinical features and predictors of in-hospital mortality in patients with acute and chronic pulmonary thromboembolism. AB - OBJECTIVE: The differences in the clinical findings of patients with acute pulmonary thromboembolism (acute-PTE) and chronic pulmonary thromboembolism (chronic-PTE) were compared, and the association between the clinical findings and prognosis in the two groups was analyzed. PATIENTS: This study included 204 patients with PTE, 139 patients with acute-PTE and 65 patients with chronic-PTE. RESULTS: There were significant differences between acute-PTE and chronic-PTE in the predisposing factors of post operation (19.4 versus 1.5%, p = 0.0003), and electrocardiographic signs such as sinus tachycardia (73.7 versus 50.9 %, p = 0.007), ST-depression (25.3 versus 9.4%, p = 0.03), right ventricular hypertrophy (20.0 versus 47.2%, p = 0.0007), and right axis deviation (3.2 versus 22.6%, p = 0.0003). Thirty-one of the 139 acute-PTE patients died from PTE, as did 17 of the 65 chronic-PTE patients. The prognosis was poor in patients older than 70 years old (p = 0.01), with stroke (p = 0.008), syncope (p = 0.01), shock (p = 0.0006), hypocapnia (PaCO2 < or = 25 torr; p = 0.0006) and an elevation in total pulmonary resistance (TPR >1,000 dyne-sec cm(-5) (p = 0.02)) in acute-PTE, and in those with syncope (p = 0.03), shock (p = 0.008), and right ventricular hypertrophy on electrocardiogram (p = 0.03) in chronic-PTE. CONCLUSION: The results of this study indicate a relationship between the clinical features of patients with acute-PTE and chronic-PTE, and the predictors of in-hospital mortality. PMID- 11197787 TI - Oral administration of fluoroquinolones in the treatment of typhoid fever and paratyphoid fever in Japan. AB - OBJECTIVE: To study the adverse reactions and therapeutic effects of fluoroquinolones to investigate whether they can be used for the treatment of patients with typhoid fever and paratyphoid fever. METHODS: The adverse reactions and therapeutic effects of fluoroquinolones were studied retrospectively in patients with typhoid fever and paratyphoid fever. PATIENTS: 58 patients (54 Japanese) with typhoid fever, 42 patients (41 Japanese) with paratyphoid fever, and 1 Japanese patient with both typhoid fever and paratyphoid fever, who were admitted in hospitals in Tokyo, Kawasaki, Yokohama, Kyoto, and Osaka from 1995 to 1998 and treated with fluoroquinolones. RESULTS: Almost 80% of the patients were treated with tosufloxacin (TFLX) and the remaining 20 % were treated with norfloxacin, ciprofloxacin, levofloxacin, or sparofloxacin. Side effects (nausea, urticaria, aphthous stomatitis) and elevation of serum amylase were found in 3.6% and 8.3 % of patients treated with TFLX, respectively, but these adverse reactions disappeared in all of these cases either with or without a change in the drug used. No adverse reactions were found in patients treated with the other fluoroquinolones. The clinical and bacteriological effects of these drugs were adequate. CONCLUSION: Though further studies still need to be performed on the fluoroquinolones other than TFLX, we can preliminarily conclude that fluoroquinolones are safe drugs and they can be recommended for the initial therapy of patients with typhoid fever and paratyphoid fever. PMID- 11197789 TI - Multiseptate gallbladder with cholelithiasis diagnosed incidentially in an elderly patient. AB - A 70-year-old woman with rheumatoid arthritis was admitted to our hospital because of gastric ulcers. Abdominal echography incidentally revealed that the patient's gallbladder was multiseptate, an extremely rare anomaly. The diagnosis was confirmed by endoscopic retrograde cholangiography. This is the 26th case of multiseptate gallbladder in the world literature, but the patient is the oldest yet recorded with this condition. Furthermore, unlike most patients with multiseptate gallbladder, she had no biliary symptoms with concomitant cholelithiasis. PMID- 11197788 TI - Paradoxical progression of biliary strictures against recovery of biochemical parameters under ursodeoxycholic acid treatment in a case of primary sclerosing cholangitis with ulcerative colitis. AB - Ursodeoxycholic acid (UDCA) treatment for primary sclerosing cholangitis (PSC) has been considered a rational therapy, though its effectiveness in the clinical course is still open to discussion. In this report, we describe a 22-year-old man with PSC at an early stage, which was associated with ulcerative colitis (UC). He showed progressive strictures of bile ducts over a 1.5-year period in spite of an improvement in the biochemical parameters by UDCA treatment. Therefore, care should be taken in interpreting the effectiveness of UDCA, because the biochemical parameters may not change in parallel with the clinical course of PSC. PMID- 11197790 TI - Radiation enteritis: a rare complication of the transverse colon in uterine cancer. AB - Radiation therapy is a powerful method for the control of cancer. The utilization of abdominal or pelvic radiation has been extended, and the incidence of radiation enteritis appears to be increasing. The majority of the induced lesions is in the distal ileum, sigmoid colon, or rectum. Reported here is an unusual case of radiation enteritis which caused a severe sequelae of stricture in the transverse colon as a long-term effect of therapeutic irradiation for uterine cancer, and required a surgical resection. PMID- 11197792 TI - Hepatitis-associated aplastic anemia and transfusion-transmitted virus infection. AB - A 17-year-old man was admitted to our hospital because of severe acute hepatitis. Serologic studies were negative for A, B, C and G hepatitis viruses. Later, he was found to be positive for transfusion-transmitted virus (TTV) DNA. He was discharged after normalization of liver function tests. Four months after the onset of hepatitis, he was re-admitted because of pancytopenia. Bone marrow findings were consistent with aplastic anemia. The anemia responded to steroid therapy. In this case, TTV was probably involved in the development of aplastic anemia. PMID- 11197791 TI - Acute fatty liver of pregnancy showing microbial infection in the liver. AB - A 24-year-old, nulliparous woman in her 30th week of pregnancy was admitted due to threatened premature delivery. Ritodrin chloride relieved the premature contraction of the uterus but jaundice and drowsiness appeared 7 weeks later. Laboratory data revealed disseminated intravascular coagulation (DIC) with intrahepatic cholestasis, and ultrasound examination showed fatty liver. The patient was diagnosed with acute fatty liver of pregnancy (AFLP). Emergency delivery by Caesarean section was performed at 37 weeks of pregnancy and the liver function and DIC improved immediately. Liver biopsy 13 days after delivery showed nuclear swelling and cytoplasmic ballooning with mild fatty deposition. These findings were relatively compatible with acute AFLP. Higher magnification and electron microscopy revealed intracytoplasmic bacteria and fungus in the residual stage. The bacterial infection could be considered related to AFLP. PMID- 11197793 TI - Percutaneous balloon pericardiotomy by the use of Inoue balloon for the management of recurrent cardiac tamponade in a patient with lung cancer. AB - A 32-year-old man with lung cancer involving pericarditis carcinomatosa underwent pericardiotomy, using an Inoue balloon dilating catheter, to create a non surgical pericardial window. The procedure was performed from the thoracic wall to the left pleural effusion and parietal pericardium under local anesthesia. The effects of non-surgical pericardial window had been maintained until this patient died from his primary disease. It is concluded that percutaneous balloon pericardiotomy is helpful in the management of massive pericardial effusions particularly in patients with malignancies and poor clinical condition PMID- 11197794 TI - Hyponatremia with increased plasma antidiuretic hormone in a case of hypothyroidism. AB - We report a 70-year-old woman with hypothyroidism and severe hyponatremia. Her plasma antidiuretic hormone (ADH) level was inappropriately high for her low plasma osmolality. Her low serum sodium level was gradually corrected by water restriction and sodium supplementation prior to the initiation of thyroid hormone replacement. After a diagnosis of Hashimoto's thyroiditis had been made, the patient was treated with levothyroxine. Following this treatment, the patient's serum sodium level increased drastically. It is suggested that the elevated plasma ADH level played an important role in the development of hyponatremia in this case. PMID- 11197795 TI - Histological changes of the pancreas in an elderly diabetic patient positive for GAD antibody. AB - We examined the histological changes of the pancreas in a 75-year-old diabetic woman who was treated with sulphonylurea for 10 years and required insulin treatment for the subsequant 10 years. She was positive for antiglutamic acid decarboxylase antibody (GAD Ab) 20 years after the diagnosis of diabetes. Her autopsied pancreas revealed disfigured islets and no beta cells. These changes were indistinguishable from those of the long-sustained type 1 diabetes mellitus, and insulitis was not found. This case suggests that diabetic patients positive for the GAD Ab, even if oral hypoglycemic agents are effective, may develop complete beta cell destruction over a long period. PMID- 11197796 TI - A mediastinal hemangioma, associated with perirenal hemangioma and congenital anomaly of the inferior vena cava. AB - In a 40-year-old man, a mediastinal hemangioma was discovered intially as a compression of the esophagus by upper gastrointestinal endoscopy. Furthermore, perirenal hemangioma and inferior vena cava (IVC) malformation were stimultaneously found. Hemangiomas, which occur in the mediastinal and perirenal area, are extremely uncommon and congenital IVC malformation, like the present case, has not been reported. We review the literature of these vascular abnormalities. PMID- 11197797 TI - Clinical experiences of stenting in patients with esophago-bronchial fistula: report of four cases. AB - The esophagorespiratory fistula is difficult to treat, and the patients' quality of life is generally poor due to suffering from dysphagia and dyspnea. We performed stent therapy in four cases of the esophagorespiratory fistula associated with esophageal cancer. Three of four patients showed improved symptoms, enabling oral liquid or food intake, although one died of dyspnea despite the therapy. The findings suggest that stent therapy is an effective method to close the esophagorespiratory fistula and to improve the patients' quality of life, although it is temporary and not a radical treatment. PMID- 11197798 TI - Good's syndrome presenting with cytomegalovirus pneumonia. AB - A 61-year-old woman who had undergone an operation for thymoma 17 years previously suddenly became dyspneic and showed bilateral pulmonary infiltrates on a chest radiograph. In the bronchoalveolar lavage fluid cells contained characteristic cytomegalic inclusion bodies, as well as cytomegalovirus DNA demonstrated by a polymerase chain reaction. Immunological findings included hypogammaglobulinemia, deficient numbers of circulating B cells, and impaired blast transformation of peripheral blood T cells in response to mitogens in vitro. Considering all of the findings, the patient was diagnosed with Good's syndrome presenting with cytomegalovirus pneumonia. PMID- 11197799 TI - Serum KL-6 as a possible marker for amiodarone-induced pulmonary toxicity. AB - Amiodarone is a useful drug for the treatment of life-threatening cardiac arrhythmias. However, amiodarone can induced pulmonary toxicity (APT) and may cause life-threatening lung damage. APT can be difficult to diagnose, but early diagnosis is important. Here, in a 51-year-old man with APT, the high serum KL-6 level was correlated with the severity of symptoms and chest X-ray findings, and it was inversely correlated with PaO2 and diffusion capacity for carbon monoxide levels. The findings suggest that the serum KL-6 level may be increased in APT and that therefore it's the determination of serum KL-6 may provide a useful indicator and/or monitoring marker of APT. KL-6 is believed to be produced and secreted by type II pneumocytes. Typical pathological findings of APT include proliferation of type II pneumocytes which may produce KL-6, and result in increased serum KL-6 levels. PMID- 11197800 TI - VEGF is causative for pulmonary hypertension in a patient with Crow-Fukase (POEMS) syndrome. AB - We report a case of Crow-Fukase (POEMS) syndrome associated with pulmonary hypertension (PH). In this case, the concentration of vascular endothelial growth factor (VEGF) was extremely high in the serum, and the levels of IL-1beta, IL-6, TNF-alpha, and thiamine, which were thought in past reports to be mediators of PH in Crow-Fukase syndrome, were normal. After prednisolone therapy, PH disappeared with a dramatic decrease in serum VEGF. Our results suggest that VEGF is closely correlated with PH in Crow-Fukase syndrome. PMID- 11197801 TI - Parietal cheiro-oral syndrome. AB - Cheiro-oral syndrome due to a parietal lesion has been reported in conjuction with a brain tumor, infarction and migraine. Only six reports of cheiro-oral syndrome due to a parietal infarction have been reported to date. We treated a 45 year-old woman with cheiro-oral syndrome due to a parietal infarction. Her sensory disturbance was characterized by paresthesia in the lower face and hand on the left side, and severe involvement of stereognosis and graphesthesia in the left hand. The pathogenesis of parietal cheiro-oral syndrome is discussed. PMID- 11197802 TI - Rapidly progressive polymyositis with elevated antiacetylcholine receptor antibody activity. AB - We report a 51-year-old woman with polymyositis accompanied by a high titer of antiacetylcholine receptor antibody. The patient presented with weakness of grip strength followed by rapidly progressive dyspnea, which required mechanical ventilation. She was treated with a glucocorticoid and came off the respirator one week later. Antiacetylcholine receptor antibody activity was elevated in the acute phase and decreased during recovery, although other signs of myasthenia gravis were negative. This patient suggested that in cases of rapidly progressive bulbar palsy and limb muscle weakness, it is necessary to include polymyositis associated with elevated antiacetylcholine receptor antibody activity in the differential diagnosis. PMID- 11197803 TI - Parkinsonian symptoms as an initial manifestation in a Japanese patient with acquired immunodeficiency syndrome and Toxoplasma infection. AB - We studied a Japanese patient who developed parkinsonian symptoms over 3 months before the diagnosis of acquired immunodeficiency syndrome. Brain MRI showed multiple lesions with mass effect and ring enhancement in the basal ganglia and subcortical white matter suggesting Toxoplasma infection. Anti-Toxoplasma therapy and highly active antiretroviral therapy for 6 months allowed improvement of parkinsonism, brain MRI findings, and immune system. PMID- 11197804 TI - Simultaneous macroamylasemia and macrolipasemia in a patient with systemic lupus erythematosus in remission. AB - We report the fourth case of simultaneous macroamylasemia and macrolipasemia. A 39-year-old woman had been treated for systemic lupus erythematosus from 1982 to 1993. She was found to have an unexplained increase in serum amylase and lipase activities since 1996. Immunoprecipitation assay showed that amylase was bound to IgA2-kappa and IgA1-kappa (IgA2 > IgA1), whereas lipase was bound to IgA1-kappa. During a follow-up period up to December 1999, the patient did not develop any additional autoimmune or lymphoproliferative disorders. In the situation of atypical clinical features associated with hyperamylasemia and hyperlipasemia, the possibility of macroenzymes should be considered. PMID- 11197805 TI - Mixed connective tissue disease with multiple organ damage: successful treatment with plasmapheresis. AB - A 24-year-old-woman with mixed connective tissue disease (MCTD) developed multiple organ failure, disseminated intravascular coagulation (DIC), metabolic acidosis, and respiratory and renal failure resulting from visceral vasospasm, so called visceral Raynaud's phenomenon. After plasmapheresis, the condition of multiple organ failure was markedly improved. The successful treatment with plasmapheresis was dependent upon the removal of immune complexes in serum and improvement of visceral circulation. Thus plasma exchange is recommended as a possible a treatment for multiple organ damage in MCTD. PMID- 11197806 TI - Polymyalgia rheumatica and type 2 diabetes mellitus complicated with electromyographic abnormalities that responded well to corticosteroid therapy. AB - A 62-year-old man who had a 14-year history of diabetes complained of low-grade fever, general malaise, pain of bilateral femurs and hip girdle, and was adniitted to our hospital. The diagnosis of polymyalgia rheumatica (PMR) was made from the clinical symptoms, elevated C-reactive protein and erythrocyte sedimentation rate. Electromyography revealed abnormalities that suggested diabetic peripheral neuropathy. However, the abnormalities were improved after starting treatment with corticosteroids (PSL). After stopping PSL, electric nerve conduction disturbance developed; therefore, it was suggested that peripheral nerve involvement due to PMR was improved by administration of PSL regardless of the existence of diabetic peripheral neuropathy. PMID- 11197807 TI - Rapidly progressive pneumonia due to Aeromonas hydrophila shortly after near drowning. AB - An 87-year-old woman died of rapidly progressive pneumonia due to Aeromonas hydrophila shortly after a near-drowning event. Autopsy showed necrotizing pneumonia and postmortem cultures of both blood and lung revealed the organism. Fulminant pneumonia should be considered in patients of a near-drowning event. PMID- 11197808 TI - Acute eosinophilic pneumonia caused by cigarette smoking. PMID- 11197809 TI - Tandospirone, a promising alternative drug in the treatment of chorea. PMID- 11197810 TI - Revised criteria for diagnosis of autoimmune hepatitis. PMID- 11197811 TI - [Vestibular symptoms and ENG findings during periods of convalescence after endolymphatic sac drainage and steroid-instillation surgery (EDSS)]. AB - Understanding the appearance of vestibular symptoms during periods of convalescence after surgery for the treatment of Meniere's disease is important for determining when a patient can return to work as well as the long-term results of the operation. We have treated 20 cases of intractable Meniere's disease with endolymphatic sac drainage & steroid-instillation surgery (EDSS) [Kitahara T, et al., Ann Otol Rhlnol Laryngol in press, 2000] and observed the subjective symptoms and objective vestibular findings using electronystagmogram (ENG) during the subsequent period of convalescence. The average postoperative durations of subjective static and evoked vestibular symptoms were 1.7 and 6.7 days, respectively. Those of spontaneous, positional and positioning nystagmus observed using ENG were 1.2, 2.0 and 7.9 days, respectively. In cases with a long history of Meniere's disease, postoperative static vestibular sensation and positional nystagmus lasted significantly longer than in cases with short histories. In cases with poorly developed temporal bony pneumatization in the area behind the posterior semicircular canal, postoperative evoked vestibular sensations and positioning nystagmus lasted significantly longer than in cases with well developed temporal bony pneumatization. Vestibular symptoms resulting from direct invasion during EDSS were considered to be slighter than those resulting from vestibular neurectomy or gentamicin treatment and almost the same as those resulting from endolymphatic sac surgery. PMID- 11197812 TI - [Seven cases of tuberculous otitis media]. AB - Tuberculous otitis media (TOM) is a variable and puzzling infectious disease that is sometimes confused with other chronic middle ear diseases. A series of 7 cases (9 ears) of TOM recently treated at Osaka Prefectural Habikino Hospital is reviewed to assess the recent features of the disease. In most cases, the pathogenetic mechanism was probably aspiration of tubercle bacilli through the eustachian tube. In most cases, abundant granulations were observed in the middle and external ears, but multiple perforations of the tympanic membrane were not seen. The manifestations were variable, such as otorrhea from the perforation and otitis media with effusion. In their early stage, most cases of TOMs due to transmission via the eustachian tube are tend to resemble otitis media with effusion. Smear tests, culture, PCR, and histopathological examinations, each of which has advantages and disadvantages, must be repeated to achieve a definitive diagnosis. Tuberculin tests can be unreliable, but a chest x-ray is indispensable whenever TOM is suspected. Antitubercular chemotherapy and 2% kanamycin earwash yielded good results. Since the classical criteria for the diagnosis of TOM are no longer valid, we propose a new criterion for diagnosis in the early stage of the disease. PMID- 11197813 TI - [Factors influencing satisfaction of cochlear implant users--a questionnaire based study]. AB - We surveyed on cochlear implant (CI) users using a questionnaire to determine how they use their CIs in daily life and to what degree they are satisfied with them. We also studied the relationship between the degree of satisfaction and speech perception score, age at operation, and deafness duration. Subjects were 37, postlingually-deafened adult CI users were subjected to this study. Average CI use per day was 13.6 hours. Some 60% of subjects understood person-to-person conversation without lipreading, but most could not communicate on the telephone, in meetings, or in noisy places, for example. Most--about 80%--were satisfied with CI, but 20% were not. Those not satisfied tended to be unable to understand person-to-person conversation even with CI and lipreading, indicating that understanding person-to-person conversation is one of the most important reasons for satisfaction in CI users. Speech recognition scores improved in all cases after implantation. Most patients with high speech recognition score-->40% in consonant recognition--were satisfied with CI, but those with recognition scores < 40% in consonant recognition, the degree of satisfaction varied. These results indicate that the degree of satisfaction in CI users does not always correspond to the degree of improvement in speech recognition score. Two patients not satisfied with CI had undergone surgery after the age of 65 years and deafness duration exceeding 20 years. Advanced age and a long deafness duration may thus reduce satisfaction with CIs. PMID- 11197814 TI - [Bilateral facial palsy in a patient with human immunodeficiency virus infection- a case report]. AB - We report a 37-year-old male with bilateral peripheral facial palsy associated with HIV infection. He was serologically tested for HIV and was found to be positive (by Western blot and ELISA). Serum chemistry studies showed elevated HIV RNA and were negative for p24 antigen. The CD4+ count was 533 cells x 10(6) per liter, with a CD4+:CD8+ ratio of 0.47. Since there was no evidence of any other underlying systemic illness, his facial palsy was considered to be secondary to HIV infection. PMID- 11197815 TI - [Comparison of combined operation and nasal CPAP treatments for sleep disorders]. AB - Uvulopalatopharyngoplasty (UPPP) and nasal CPAP are used for the treatment of obstructive sleep apnea syndrome (OSAS) in different institutions. Although OSAS results from an abnormality in the soft-palate, almost no reports have been made on the selection of UPPP or nasal CPAP procedures according to the type of abnormality. The most probable reason for this is that a comparison of treatment methods in individuals cases is difficult. We performed CPAP titration before and after operations, and compared the treatment methods, and evaluated the medical therapy. METHOD: A sleep polygraph was performed on the first night, and cases diagnosed as OSAS received CPAP titration on the second night. The blocked region was identified by endoscopic examination. The results of the operation were evaluated after 1-2 months, and apnea hypopnea index (AHI) improvements of less than 50% received a second CPAP titration. RESULTS: The operation results were poor for cases where endoscopic examination showed full-circumference palatal type, and good for soft palate and tonsillar type abnormalities. When endoscopic examinations were performed in conjunction with nasal CPAP, the treatment was observed to act on the soft palate and expand the air way in all cases. Nasal CPAP was effective in cases with full-circumference palatal abnormalities because in these cases, the pressure was caused by inflamma. Combined medical treatments were effective in cases where CPAP alone was ineffective because the pressure was too high. PMID- 11197816 TI - [Intracellular calcium kinetics after odorant stimulus in olfactory receptor cells isolated from mice]. AB - cAMP and IP3 act as secondary messengers in olfactory signal transduction and when activated, stimulate calcium levels in olfactory receptor cells. Little is known however, about the causal mechanism. We studied calcium kinetics in mouse olfactory receptor cells after odorant stimuli. Olfactory receptor cells were isolated from female BALB/c mice, treted with trypsin, and stained with Fura 2/AM. Changes in intracellular Ca2+ concentrations in stained cells were measured with a fluorescent microscopic image-processing device (ARGUS-50; Hamamatsu Photonix, Japan). We found that intracellular Ca2+ concentrations rose after exposure to a set of odorants, including 3-ethoxy-4-hydroxy-benzaldehyde, caprylic acid, heptanoic acid, nonanoic acid, eugenol, phenethyl alcohol, and n amyl acetate. Adding 2', 5'-dideoxyadenosine, a cAMP inhibitor, beforehand suppressed olfactory receptor cell response to odorants. Intracellular Ca2+ concentrations increased substantially in response to stimulation by odorants in calcium-free Ringer's solution, but only a slight increase was seen in intracellular calcium concentration in response stimulation by a high concentration of K+ (145.6 mM) in calcium-free Ringer's solution. The increase in intracellular Ca2+ concentration after odorant stimuli was suppressed when olfactory receptor cells were pretreated with ryanodine, which releases Ca2+ from intracellular stores. These findings suggest that elevated Ca2+ concentrations may be involved in releasing Ca2+ from intracellular calcium stores in mouse olfactory receptor cells, in which cAMP functions as a secondary messenger in olfactory signal transduction. PMID- 11197817 TI - Differences in left ventricular response between rheumatic and myxomatous mitral valve disease following mitral valve replacement. AB - OBJECTIVE: We studied whether differences exist between hearts having rheumatic mitral valves and those having myxomatous mitral valves, in functional, geometrical, and mass changes in the left ventricle after mitral valve replacement. METHODS: Patients who underwent mitral valve replacement without preservation of annular-papillary continuity for pure mitral incompetence were classified into rheumatic and myxomatous based on valvular histopathology. Echographic data measured before surgery was compared to that about 3 weeks after surgery. RESULTS: In the rheumatic group, ejection fraction decreased from 57.5 +/- 10.8 to 47.7 +/- 12.0, indexed left ventricular internal dimension in systole (mm/m2) from 24.7 +/- 6.8 to 20.7 +/- 6.2 (P = 0.0001), and left ventricular mass index (g/m2) from 205 +/- 55 to 138 +/- 54 (P = 0.0002). In the myxomatous group, ejection fraction decreased from 60.4 +/- 11.6 to 39.7 +/- 14.5 (P = 0.0001), indexed left ventricular internal dimension in systole from 24.2 +/- 5.6 to 23.1 +/- 5.5, and left ventricular mass index from 195 +/- 83 to 111 +/- 72 (P = 0.0004). Mean wall thickness index and relative wall thickness showed significant differences between the two groups postoperatively but no significant difference preoperatively. CONCLUSION: Hearts dilated due to chronic mitral incompetence respond differently after valvular replacement with total chordal excision depending on whether a rheumatic or myxomatous mitral valve is involved. PMID- 11197818 TI - Ipsilateral recurrence frequency after video-assisted thoracoscopic surgery for primary spontaneous pneumothorax. AB - OBJECTIVE: We retrospectively evaluated the results of video-assisted thoracoscopic surgery for primary spontaneous pneumothorax and recurrence. METHODS: A series of 424 patients with primary spontaneous pneumothorax were treated by video-assisted thoracoscopic surgery-289 with an ipsilateral recurrent episode, 88 with persistent air leakage for 7 days or longer, 34 with a contralateral episode, 9 with hemopneumothorax, and 4 with tension pneumothorax. The commonest management was stapling of an identified bleb, undertaken in 375 patients (88.4%). Pleural abrasion was conducted in 250 (59.0%), but the abraded area was one-third or less of the thoracic cavity in 187 (74.8%). RESULTS: No operative deaths occurred. Revisional thoracotomy was required in 1 patient with postoperative bleeding and another with incomplete postoperative lung reexpansion; 26 had prolonged air leakage, but none required revisional thoracotomy. During a mean follow-up of 31.4 months, ipsilateral pneumothorax recurred in 40 patients (9.4%), with 26 (65.0%) having recurrence within 1 year postoperatively. A video-assisted thoracoscopic surgery was conducted again in 8, and thoracotomy in 14. CONCLUSIONS: The ipsilateral recurrence of primary spontaneous pneumothorax after video-assisted thoracoscopic surgery was high at 9.4%. If video-assisted thoracoscopic surgery is to be considered as a treatment for spontaneous pneumothorax, we must therefore reduce postoperative ipsilateral recurrence by training practitioners not to overlook blebs during the procedure and/or consider widening the area of pleurodesis. PMID- 11197819 TI - Prevention of paraplegia in transluminally placed endoluminal prosthetic grafts for descending thoracic aortic aneurysms. AB - OBJECTIVE: To evaluate the efficacy of a temporary balloon occlusion test for the prevention of paraplegia following transluminally placed endoluminal prosthetic grafts for descending thoracic aortic aneurysms. SUBJECTS AND METHODS: Two occlusion balloons were inserted via the brachial and femoral arteries and positioned in the proximal and distal neck of the descending thoracic aortic aneurysms using fluoroscopy. After temporary occlusion of the thoracic aorta by inflation of both the proximal and distal balloons, the evoked spinal potential was measured for 15 mins. A maximum amplitude during temporary balloon occlusion test decreasing by more than 20% of the pre-balloon occlusion level was considered to be significant, enough to not perform transluminally placed endoluminal prosthetic grafts, but instead an open repair. The test was applied in 12 cases (9 males and 3 females, 50-86 years old). All aneurysms were located between the Th6 and Th12 with a maximum diameter of 40-70 mm, and average of 56 mm. RESULTS: The changes in maximum amplitude of evoked spinal potential remained within 20% of the value before balloon occlusion in 11 cases. Transluminally placed endoluminal prosthetic grafts were performed in these 11 cases and no instance of paraplegia or other complication relating to the test was observed. Deployment of stent-grafts was successful in 10 cases (91%). CONCLUSION: It is suggested that the preoperative measurement of evoked spinal potential during temporary balloon occlusion is clinically useful for the assessment of the risk to paraplegia occurring in transluminally placed endoluminal prosthetic grafts. PMID- 11197820 TI - Sarpogrelate reduces mechanical hemolysis in patients with heart valve prostheses. AB - OBJECTIVE: We evaluate the clinical efficacy of sarpogrelate, an antiplatelet drug that improves red blood cell deformability, to reduce the intravascular hemolysis problems suffered frequently by patients implanted with heart valve prostheses. SUBJECTS: Subjects were 34 patients undergoing mechanical heart valve replacement and having serum lactate dehydrogenase concentrations 20% above the maximum normal range. METHOD: Sarpogrelate was given daily, 100 mg orally for the first 6 months and 200 mg thereafter. RESULTS: Average serum lactate dehydrogenase decreased significantly from 423 +/- 108 IU/l, to 391 +/- 83 IU/l with the 100 mg dose, and to 361 +/- 86 IU/l with the 200 mg dose. The percentage of reticulocytes decreased from 15.5 +/- 5.3/1000 to 15.3 +/- 5.7/1000 at the 100 mg dose and 13.1 +/- 4.0/1000 at the 200 mg dose. Serum iron concentrations increased significantly from 63.2 +/- 24.8 micrograms/dl to 76.2 +/- 16.2 micrograms/dl at the 100 mg dose, and to 70.9 +/- 26.2 micrograms/dl with the 200 mg dose. CONCLUSION: Sarpogrelate is a useful drug for patients with implanted heart valve prostheses and subsequent high serum lactate dehydrogenase because it works as an antiplatelet drug and reduces mechanical hemolysis. PMID- 11197821 TI - Freehand cryopreserved mitral valve allograft with flexible ring in the pig. AB - OBJECTIVE: Cryopreserved valve allografts have proven satisfactory in aortic and pulmonary positions but not mitrally because of the difficulty in properly aligning the mitral valve allograft due to the complex subvalvular apparatus. To make the surgical procedure easier, we developed a freehand cryopreserved mitral valve allograft with a flexible ring. METHODS: Whole cryopreserved mitral valve allografts with the papillary muscle, chordae, and leaflets from donor pigs were implanted mitrally in recipient pigs under cardiopulmonary bypass divided into 2 experimental groups; control allografts without the ring (n = 6) (CA group) and allografts with a flexible ring (n = 7) (RA group). Postimplantation hemodynamics and valvular function were evaluated by measuring arterial pressure, left ventricular end diastolic pressure, and left atrial pressure and by evaluating 2 dimensional echocardiography. Allografts were evaluated pathohistologically after cryopreservation and surgery by light microscopy. RESULTS: Hemodynamics did not differ significantly between groups. Aortic cross-clamping and Cardiopulmonary bypass times were significantly shorter in the RA group than the CA group (p < 0.05). Pigs requiring optional procedures with sutured annuloplasty and valvuloplasty numbered more in the CA group than the RA group. Postoperative echocardiography showed satisfactory mitral valve opening in diastole and good leaflet coaptation in systole in both groups. Light microscopic examination of cryopreserved allografts after surgery showed almost normal structures. CONCLUSIONS: Acute hemodynamic function and morphology of freehand cryopreserved valve allografts implanted mitrally in pigs proved acceptable. Adaptation of the flexible ring to allografts might be useful for technical benefit to facilitate accurate positioning of mitral subvalvular apparatus at implantation. PMID- 11197822 TI - Cerebral protection selection in aortic arch surgery for patients with preoperative complications of cerebrovascular disease. AB - OBJECTIVE: Retrograde perfusion is gaining acceptance as a means of cerebral protection, but it remains unclear how long the brain is protected and whether it is effective in patients with preoperative cerebrovascular disease. METHODS: From January 1989 to August 1999, 205 patients--118 male and 87 female patients who ranged 12 to 86 years old, mean: 65.5 years old--underwent surgery at our hospital for aortic arch aneurysm using cerebral protection. We focused on mortality, stroke incidence and perioperative risk factor between 2 groups- selective cerebral and retrograde cerebral perfusion--also studying patients with preoperative cerebrovascular disease that influenced postoperative stroke. RESULTS: The hospital mortality was 11.7% (selective cerebral perfusion group: 12%, retrograde group: 10.9%). Stroke occurred in 11 patients (5.3%), 4.7% in the selective cerebral perfusion group and 7.3% in the retrograde group. Preoperative cerebrovascular disease does not appear to be a risk factor for postoperative brain damage in aortic arch surgery. Regarding total replacement of the aortic arch, the incidence of postoperative brain damage in the retrograde group with preoperative cerebrovascular disease was higher than that in another group (p = 0.072). Cardiopulmonary bypass time and selective cerebral perfusion time in the patients with postoperative stroke were significantly longer than that in non stroke group. CONCLUSIONS: Preoperative cerebrovascular disease did not appear to be a risk factor in postoperative neurological deficit in the selective cerebral perfusion group. Prolonged selective cerebral perfusion time and cardiopulmonary bypass time may, however, lead to brain edema and cause neurological deficit. PMID- 11197823 TI - Standard coronary artery bypass grafting and beating heart bypass. Indications and long-term results. AB - OBJECTIVES AND METHOD: We have performed 225 cases of coronary artery bypass grafting (CABG), between October 15 1995 and September 8 1999. We have evaluated the operative results of 121 cases (53.8%) of conventional CABG and 104 cases (46.2%) of minimally invasive coronary artery bypass grafting performed during this period. The average numbers of bypassed grafts was 3.45 for conventional CABG, and 1.41 for minimally invasive coronary artery bypass grafting. Sixty seven right internal thoracic arteries, 145 left internal thoracic arteries, 71 gastroepiploic arteries, 38 radial arteries and 12 saphenous veins were used for conventional CABG, and 29 right internal thoracic arteries, 81 left internal thoracic arteries, 18 gastroepiploic arteries, 3 radial arteries, 10 saphenous veins and 2 inferior epigastric arteries were used for minimally invasive coronary artery bypass grafting. The total number of 303 grafts were anastomosed to 417 coronary arteries for conventional CABG, and 143 grafts were anastomosed to 147 coronary arteries for minimally invasive coronary artery bypass grafting. RESULTS: Although two saphenous veins were occluded, the early postoperative patency rate was 100% for conventional CABG using right internal thoracic arteries, left internal thoracic arteries, gastroepiploic arteries and radial arteries. Three site of stenosis in 18 left internal thoracic arteries and 2 in 16 right internal thoracic arteries were recognized in minimally invasive coronary artery bypass grafting without the use of stabilizers. One site of stenosis in 63 left internal thoracic arteries was recognized in minimally invasive coronary artery bypass grafting with the use of stabilizers. CONCLUSION: The use of stabilizers enables adaptation of the minimally invasive coronary artery bypass grafting procedure to a wider range of coronary artery bypass procedures, and a higher graft patency can be expected. PMID- 11197824 TI - Minimally invasive coronary artery bypass grafting for the left anterior descending coronary artery. AB - OBJECTIVE: A single surgeon conducted One hundred and twelve patients underwent minimally invasive direct coronary artery bypass grafting for the left anterior descending coronary artery 112 patients at Yamato Seiwa Hospital from September 1996 until August 1999. METHODS: All procedures were performed via left anterior short thoracotomy using a stabilizer during graft anastomosis. RESULTS: No operative deaths occurred but 3 patients died while hospitalized due to noncardiac events. Graft occlusion was seen in 3 patients early postoperatively. Other angiography graft failure such as stenosis was seen in 11 patients. Occlusive lesions of other coronary arteries occurred in 77 patients (69%) and 53 patients underwent percutaneous transluminal coronary angioplasty the pre/postoperatively for those lesions. CONCLUSIONS: These results suggest that minimally invasive direct coronary artery bypass grafting is seen by cardiologists as a reasonable form of revascularization in conditioned patients having left anterior descending artery lesion, and that minimally invasive direct coronary artery bypass grafting has a spectrum of candidates different from that of conventional surgical revascularization for the coronary artery. PMID- 11197826 TI - Neuroblastoma resection in an adult with a 10-year history of chest-mass shadow. AB - Neuroblastoma is rare in adults. We encountered this tumor in an asymptomatic 21 year-old man with a 10-year history of a mass-like shadow in chest radiography. Diagnosis was confirmed after resection, and 60 Gy radiation therapy was started. One year later, the patient has no clinical or radiological evidence of recurrence. PMID- 11197825 TI - Clinical assessment of unilateral pulmonary artery occlusion test with dobutamine infusion. Expansion of surgical indications in patients with primary lung cancer and impaired cardiopulmonary functions. AB - OBJECTIVES: We evaluated the possibility of expanding indications for pulmonary resection based on an assessment of the pressure-flow relationship in pulmonary circulation. METHODS: In 6 of 28 lung cancer patients whose total pulmonary vascular resistance index exceeded the threshold during unilateral pulmonary artery occlusion testing, we conducted unilateral pulmonary artery occlusion testing with dobutamine administration, followed by lung resection. We studied hemodynamics during testing and derived a new indication for pulmonary resection from the postoperative course. RESULTS: Cardiac output was 3.82 +/- 0.74 l/min before testing, 3.66 +/- 0.76 l/min during pulmonary artery occlusion testing, and 5.92 +/- 1.78 l/min during unilateral pulmonary artery occlusion testing with dobutamine infusion. The total pulmonary vascular resistance index was 890 +/- 350 dyne.sec.cm-5.m2 before testing, 1170 +/- 320 dyne.sec.cm-5.m2 during testing, and 800 +/- 160 dyne.sec.cm-5.m2 during testing with dobutamine infusion. Cardiac output increased (p = 0.014) during unilateral pulmonary artery occlusion testing with dobutamine infusion, and the total pulmonary vascular resistance index significantly decreased (p = 0.034). Of the 4 patients eligible for lobectomy, 2 underwent the procedure--one undergoing segmentectomy in which pulmonary metastasis was found during surgery and the other undergoing radiotherapy for cN2 disease with chest wall invasion. Of the 2 initially ineligible for lobectomy, one underwent partial pulmonary resection and the other underwent lobectomy because the total pulmonary vascular resistance index was less than 800 dyne.sec.cm-5.m2 during selective pulmonary artery occlusion testing with dobutamine infusion, indicating eligibility for lobectomy. No severe complications of cardiopulmonary function failure after surgery occurred in any of the 5 cases. CONCLUSIONS: Unilateral pulmonary artery occlusion testing with dobutamine infusion is useful in determining patient eligibility for pulmonary resection. PMID- 11197827 TI - Coronary surgery through partial sternotomy in a patient with tracheostoma. AB - We report successful coronary artery bypass grafting through a lower partial sternotomy for a patient with a tracheostoma. He required a tracheotomy for serious laryngeal edema which developed during anesthetic induction prior to elective conventional coronary surgery. A safe alternative approach, comprising a lower midline skin incision with a lower partial sternotomy distant from the stoma, facilitated coronary artery bypass grafting to the left and right coronary arteries after four weeks. PMID- 11197828 TI - Benign mesenchymoma of the mediastinum. AB - We report our recent experience of a rare case of a benign mesenchymoma in the mediastinum. A 24-year-old man was admitted to our hospital with an abnormal shadow on chest X-ray. A chest computerized tomography scan and magnetic resonance imaging showed an anterior mediastinal mass along the right border of the pericardium. The tumor was surgically resected. It was yellow on the surface, 12.5 x 10.0 x 3.8 cm in size, and 230 g in weight. The histopathological diagnosis was a benign mesenchymoma. The postoperative course was uneventful. A search of the literature revealed that a benign mesenchymoma in the mediastinum is extremely rare. It seems to be difficult to reach a definitive diagnosis preoperatively. Surgical resection can confirm the diagnosis, and is curative. PMID- 11197829 TI - Primary tracheal mucosa-associated lymphoid tissue lymphoma accompanying lung cancer. Common tumorigenesis or coincidental coexistence? AB - We report a 67-year-old patient with coexistent tracheal non-Hodgkin's lymphoma and lung cancer the first case, to our knowledge, of this concomitant incidence in the literature. Chest radiography showed a mass in the right lung and pulmonary fibrosis. Biopsy of the unanticipated tracheal irregularity revealed non-Hodgkin's lymphoma, compatible with mucosa-associated lymphoid tissue lymphoma. After right upper lobectomy, chemotherapy for non-Hodgkin's lymphoma was conducted, but the patient died 11 months postoperatively of pulmonary fibrosis. Pulmonary fibrosis was suspected of having progressed from drug-induced pneumonitis caused by anticancer drugs. A common tumorigenetic factor may thus exist between tracheobronchial mucosa-associated lymphoid tissue lymphoma and lung cancer. PMID- 11197830 TI - Hypertrophic obstructive cardiomyopathy associated with mitral regurgitation due to infective endocarditis. AB - A 25-year-old woman treated for hypertrophic obstructive cardiomyopathy and suffering from mitral regurgitation due to infective endocarditis was referred to our department for surgery. Preoperative examinations revealed asymmetric septal hypertrophy, a large left ventricular outflow gradient (100 mmHg), and perforation of the anterior mitral leaflet resulting in severe mitral regurgitation. The entire mitral complex was resected and septal myectomy conducted to dilate the left ventricle. A bioprosthetic valve was then implanted. Although postoperative heart failure was severe, cardiac function has gradually recovered. The left ventricular outflow gradient has decreased to 8 mmHg, the diastolic left ventricular diameter has increased from 26 to 30 mm, and her New York Heart Association classification has improved from IV to I. PMID- 11197831 TI - Early small cell lung cancer with extensive inflammation and scar formation. AB - A 56-year-old man, at one year before his first visit to our hospital, had presented cough, stridor and chest pain, and expectorated a mass, resulting in prompt disappearance of the symptoms. He was afflicted with recurrent symptoms, and the bronchoscopy showed a polypoid tumor occluding the right lower bronchus. The tumor was resected via bronchoscopy, which revealed histologically small cell carcinoma with significant inflammation and scar formation. The tumor was macroscopically the same as the one that had been expectorated by the patient at one year previously. A right lower lobectomy was conducted, but the specimen demonstrated no residual tumor. Tumor invasion into the bronchial wall was therefore limited within the submucosal layer for more than a year. Finally, the present tumor was diagnosed as an early small cell lung cancer with a characteristic of self involution. With no adjuvant treatment, the patient is well without tumor recurrence at 3 years to date after the surgery. PMID- 11197832 TI - [Liver intervention]. AB - Interventional radiology is now widely performed for the treatment of liver tumors, because surgery is sometimes limited by poor liver function. Transcatheter arterial chemoembolization(TACE) is an effective therapy for hepatocellular carcinoma. Lipiodol TACE shows a strong antitumor effect because of the overflow of excess iodized oil into the portal veins, and segmental TACE is recommended to avoid deteriorating liver function. Selective CT arteriography is performed in order to decide on the treatment area, and TACE under CT guidance leads to effective results in terms of dense accumulation of the chemotherapeutic drug in the individual tumors that are affected by the ischemic state and anticancer drugs. Percutaneous microwave or radiofrequency coagulation therapy is adequate for a few of the hypovascular tumors. Excessive coagulation through the needle tract is indispensable in these therapies, and precisely designed puncture is necessary to minimize damage to the liver parenchyma. Selective chemotherapy to the tumor-bearing organ is the first step in a number of liver tumors. Continuous intra-arterial infusion chemotherapy is performed for multiple liver metastases. The reservoir implantation technique is percutaneously achieved via the left subclavian artery under ultrasound guidance, without the exposure of an artery in the incision method, which can induce thrombus formation. PMID- 11197833 TI - [Biopsy]. AB - We reviewed the current devices, techniques, guiding images, indications and complications of needle biopsy with CT guidance. The development of new devices such as automated cutting needle has enabled radiologists to obtain tissue specimens of good quality at biopsy. Techniques such as the tandem or coaxial method ensure more a more accurate biopsy route. And helical CT and CT fluoroscopy have markedly shortened the time required for needle biopsy. However, we sometimes encounter minor complications, and rarely major ones, during and after needle biopsy. Some of these complications may be caused by malpractice. Therefore it is important always to pay attention to the possibility of complications of needle biopsy and to minimize radiation exposures from CT fluoroscopy. PMID- 11197834 TI - [Radiation exposure to patient and radiologist during transcatheter arterial embolization for hepatocellular carcinoma]. AB - PURPOSE: To evaluate radiation exposure to patients and radiologists during transcatheter arterial embolization(TAE) for hepatocellular carcinoma. MATERIALS AND METHODS: In 39 TAE procedures performed at eight institutes, skin doses were evaluated with thermoluminescence dosimeters at the patient's back(entrance surface) and lower abdomen, and at the radiologist's forehead and abdomen. Real time dosimeters were also used to evaluate patient skin dose. RESULTS: The patients' mean entrance surface dose was 973 +/- 681 mGy(range, 185 to 3543 mGy) with the mean fluoroscopic time of 21 minutes and 6 digital subtraction angiography(DSA) acquisitions. The dose at the patients' lower abdomen was 0.98 +/- 0.77 mGy. Doses for the radiologists were 0.04 +/- 0.04 mGy at the forehead and 0.15 +/- 0.19 mGy and 0.005 +/- 0.01 mGy at the abdomen over and under the apron, respectively. Fifty-six percent of the patients' skin dose was from DSA and 44% from fluoroscopy. CONCLUSIONS: Patient skin dose may occasionally exceed the dose for transient erythema. Because a patient may have repeated TAEs, skin doses or X-ray conditions should be recorded. The exposed doses of radiologists were considered to be acceptable with proper techniques. Further efforts to reduce radiation should be directed toward both DSA and fluoroscopy. PMID- 11197835 TI - [Study of the radioprotective effects of TMG on teratogenic malformations in irradiated mice]. AB - ICR mice fetuses in the organogenesis stage were used to clarify experimentally the mechanism of the protective effect of vitamin E derivant (TMG: 2-(alpha-D Glucopyranosyl) methyl-2, -5, -7, -8-Teramethylchorman-6-working woman) on the effects of radiation. The authors paid careful attention to radiation, and the radioprotective effects of TMG on the induction of malformations was examined. Radiation is an important consideration because of its widespread use in the areas of medicine, nuclear energy, and industry. Malformations induced by radiation at the organogenesis stage, skeletal malformations, and the effects at the cellular level of embryos were examined in this research. Further, the mechanism of the protection effect of TMG against radiation-induced malformations was analyzed and observed experimentally. Thus, this study was done to provide fundamental data on the radioprotective agent TMG. It was clear that TMG exerted radioprotective effects against embryonic death and the rate of teratogenesis when administered before exposure. Such effects were also exerted against skeletal malformations and fetal body weight. In summary, radioprotective effects were observed at the whole-body level as well as at the cellular level. PMID- 11197836 TI - [Development of DICOM image viewing software for efficient image reading and evaluation of distributed server system for diagnostic environment]. AB - To construct an efficient diagnostic environment using computer displays, the author investigated the time of network transmission using clinical images. In our hospital, we introduced optical-fiber 100Base-Fx Ethernet connections between 22 HIS-segments and one RIS-segment. Although Ethernet architecture is inexpensive, the speed of image transmission becomes 2371 KB/sec. (4.6 CT slice/sec.) in the RIS-segment and 996 KB/sec. (1.9 CT-slice/sec.) from the RIS segment to HIS-segments. Because one examination is transmitted in one minute, it does not disturb image reading. Otherwise, a distributed server system using inexpensive personal computers helps in constructing an efficient system. This investigation showed that commercially based Digital Imaging and Communications in Medicine(DICOM) servers and RSNA Central Test Node servers are not so different in transmission speed. The author programmed and developed DICOM transmission and viewing software for Macintosh computers. This viewer includes two inventions, dynamic tiling window system (DTWS) and window binding mode(WBM). On DTWS, windows, tiles, and images are independent objects, which are movable and resizable. The tile-matrix is changeable by mouse dragging, which realizes suitable tile rectangles for wide-low or narrow-high images. The arranging window tool prevents windows from scattering. Using WBM, any operation affects each window similarly. This means that the relationship of compared images is always equivalent. DTWS and WBM contribute greatly to a filmless diagnostic environment. PMID- 11197837 TI - [A study of entrance surface dose with CR and film/screen systems, and analysis of the X-ray conditions for chest radiography]. AB - Several previous studies have indicated that the medical exposure dose(entrance surface dose) is lower with Computed Radiography(CR) than with the Film/Screen(F/S) system. We conducted a questionnaire survey of 1,297 hospitals regarding the radiation exposure conditions of X-ray examinations. From the survey results, we calculated the entrance surface dose(first quartile, median, third quartile, and mean) using the NDD calculation method. In the case of chest radiography(adult patients) by CR, the entrance surface dose was 150% of the median value for the overall examination and 160% of the median value for orthochromatic screen systems. The CR exposure set-up using a lower voltage and higher mAs than the F/S method was found to result in a high entrance surface dose. We also found a difference in patient dose among hospitals using CR. Mean surface dose in CR system was 0.12 mGy in a quartile, 0.19 mGy in the middle and 0.27 mGy in the third quartile. Among the hospitals which showed higher doses of third quatile them above mentioned, dose differences of a quartile were distributed 2 to 10 times higher them mean exposure doses. PMID- 11197838 TI - [Molecular genetic mechanism of the kidney cancer]. AB - The oncogenic mechanisms of renal cell carcinoma(RCC) are becoming elucidated with recent advances in molecular biology. von Hipple-Lindau disease(VHL) tumor suppressor gene is mutated and inactivated frequently in clear cell type RCCs. The VHL protein forms a complex which shows a ubiquitin ligase activity. The lost of the ubiquitin ligase activity of VHL protein may be a key step for clear cell tumorigenesis. Papillary renal cell carcinomas are caused by activating mutation in the tyrosine kinase domain of the MET gene. This tumorigenic pathway is regulated by c-Src. Immunogene therapies have been started for the patients with advanced RCC. The information based on microarray and Serial Analysis of Gene Expression(SAGE) will provide novel diagnosis and therapy which focus on the tumorigenic mechanism of RCC in the near future. PMID- 11197839 TI - [Overview on the millennium genome project]. AB - Millennium genome project had started 2000 April as a national research project. In this project, analysis of single nucleotide polymorphism of human genome and application of its information on prevention, diagnosis and treatment of major diseases, and on drug development, regenerative medicine, and analysis of rice genome are included. This project is scheduled to complete by 2004. Since large amount of research money and research power is going to be poured to this project, fruitful results are a national expectation. PMID- 11197840 TI - [Gene therapy for breast cancer]. AB - Not only the local treatments like surgery and radiation but also the systemic treatments like chemotherapy and hormone therapy are rather effective on both primary and metastatic breast cancer patients. Nevertheless, the curativity and survival of this disease have been not satisfied yet. The difficulties of the treatment seems the emergence of drug-resistant cells and the low immunity of the host. Gene therapy offers a potentially useful approach for the treatment of breast cancer. The approaches of gene therapy for breast cancer that are now undergoing as clinical protocols in USA can be divided into three strategies: (1) approaches that alter the metabolic or signaling pathways within the breast cancer cell; (2) approaches designed to enhance the immune response to the tumor cells(immuno gene therapy); and (3) approaches that use the drug-resistant gene with chemotherapy. According to the new biology of breast cancer by Fisher, the systemic treatments are more important. Immuno-therapy seems especially promising in this field. Moreover, the immuno gene therapy is hopeful that could overcome the difficulties like heterogeneity and low immunogenicity of breast cancer cell. PMID- 11197841 TI - [Perspectives on postgenome medicine: Neurodegenerative disease]. AB - The genes of the majority neurodegenerative disorders have been identified for the past decade. Diseases of early onset are usually transmitted as autosomal recessive trait and caused by the deficiency of the gene products, becoming good candidates for gene or protein transfers. Late onset diseases are usually transmitted dominantly where the gains of function by the mutant gene accumulate into specific lesion. The pathophysiology following gene mutation need to be clarified for the therapeutic approach. Recent progresses on neurodegenerative mechanism have specified crucial targets for the treatments. Stimulation to intrinsic mechanisms, i.e., chaperon, ubiquitin-proteasome system and stress response in endoplasmic reticulum and/or antagonize the toxic cascade by caspases, mitochondria insufficiency are argued as therapeutic targets, hoping that in this decade we can propose effective therapies for these devastating disorders. PMID- 11197842 TI - [Perspectives on postgenome medicine: Gene therapy for AIDS]. AB - Following the introduction of HAART(highly active anti-retroviral therapy) marked decreases in AIDS-related morbidity and mortality have been observed. Despite of the clinical success, recent work suggests that there are persistent viral replication in whom plasma HIV-RNA is consistently below detectable level. Furthermore, some experts even suggest that it will be difficult for many of the patients to continue the HAART because of the long-term side effects and drug resistance. Recent studies that supported the correlation of HIV-specific CD4-T cell(helper) response with the control of viral replication in vivo have promoted the development gene-based immunotherapy. However, further elucidation of viral pathogenesis in the patient under HAART will be required to develop the immunotherapeutic interventions. PMID- 11197843 TI - [Gene therapy for acute myocardial infarction]. AB - For patients with myocardial infarction, direct angioplasty(PTCA plus stent implantation) has become common practice in Japan. For a better prognosis, inhibition of thrombosis and restenosis in the afflicted coronary artery, salvage of ischemic myocardium, and suppression of myocardial remodeling are all highly desirable. Transfer of genes for molecules appropriate for each of the above pathological conditions is a potential effective therapy. The combined use of a recombinant protein and gene transfer of anti-thrombosis molecule into the injured artery may be an effective and practical local therapy without systemic side-effects. Angiogenesis gene therapy with an aid of endothelial progenitor cells will soon be used in the clinic, while sometime in the future replacement of the myocardial infarct with engineered fresh tissue could be the ultimate therapy. PMID- 11197844 TI - [Gene therapy for cardiomyopathy]. AB - Cardiac transplantation has become accepted therapy for a number of patients with severe cardiomyopathy. The cellular cardiomyoplasty is expected as an alternative therapy for cardiomyopathy. The experimental foundation was laid for the approach to cellular cardiomyoplasty--the molecular and cellular treatment of cardiomyopathy by augmentation, regeneration or replacement of cardiomyocytes--by experiments in cardiac gene transfer and transgenic animals. Recently, cardiomyocyte has been reported to be generated from embryonic stem cell or marrow stromal cell in vitro. However, differentiation from non-cardiomyocyte to cardiomyocyte cannot be controlled completely yet. It is now under investigation mainly in an experimental setting. For successful gene therapy, not only characterization of proper targets but also elimination of undesirable side effects are indispensable. PMID- 11197845 TI - [Gene-therapy for peripheral vascular diseases]. AB - The prognosis for patients with chronic critical leg ischemic is often poor. The treatment of peripheral vascular disease, although greatly improved over recent decades by drug medication, surgical and minimally-invasive techniques, remains limited by vascular proliferative lesions and by our inability to modulate the progression of native disease. The therapeutic angiogenesis is now the most expected therapy for peripheral vascular diseases. This review explores some of concepts and methods of therapeutic angiogenesis including gene therapy using angiogenic growth factor such as VEGF and basic FGF and an implantation of bone marrow derived endothelial progenitor cells. PMID- 11197846 TI - [Possible pathogenesis of rheumatoid arthritis]. AB - Rheumatoid fibroblast-like synoviocytes characteristically proliferate in an anchorage-independent manner, and are deeply implicated in cartilage destruction. Our previous results showed that rheumatoid synoviocytes expressed Fas ligand and were induced apoptosis by anti-Fas antibody treatment. In addition, several transcriptional factors, such as NF kappa B and AP-1 significantly activated in rheumatoid synoviocytes. We are now clarifying the pathogenesis of RA with the method, yeast two-hybrid system as 'post genome' strategy. We recently found that several factors that related with cell differentiation highly expressed in rheumatoid synoviocytes. In this report we discuss possible pathogenesis of RA based on our recent data and application to the therapy tool against RA. PMID- 11197847 TI - [Persectives on postgenome medicine: Gene therapy for liver cirrhosis]. AB - Liver cirrhosis is the irreversible end result of chronic liver disease, characterized by diffuse disorganization of the normal hepatic structure of regenerative nodules and fibrotic tissue. It is associated with prominent morbidity and mortality, and is induced by many factors. The ideal strategy for the treatment of liver cirrhosis should include prevention of fibrogenesis, stimulation of hepatocyte mitosis, and reorganization of the liver architecture. We have developed a novel gene therapy approach for rat liver cirrhosis by muscle directed gene transfer of hepatocyte growth factor(HGF). HGF gene transduction inhibited fibrogenesis and hepatocyte apoptosis, and also produced resolution of fibrosis in the cirrhotic liver. Thus, HGF gene therapy may be potentially useful for the treatment of patients with liver cirrhosis, which is otherwise fatal and untreatable by conventional therapy. PMID- 11197848 TI - [Perspectives on postgenome medicine: Gene therapy for diabetes mellitus]. AB - Several topics in diabetes research and practice in the coming 'post-genomic era' are described. 1) Insulin-producing pancreatic beta cells are a plausible target of gene therapy for type 1 diabetes mellitus. Functional genomics will reveal the mechanism of beta cell growth and regeneration. Attempts are being made to differentiate non-beta cells(including ES cells) into insulin-producing cells in vitro or in vivo. 2) Very recently, an intron variation in calpain 10 gene was found to be associated with type 2 diabetes, which confirmed the importance of SNPs in common diseases. More and more SNPs related to type 2 diabetes will be discovered and, in combination with pharmacogenomics, 'personalized medicine' based on SNP information of the individuals will hopefully be achieved. PMID- 11197849 TI - [Gene therapy for the treatment of hypertension]. AB - Gene therapy for hypertension is very important for the next generation of antihypertensive drugs. Important question regarding vector-related limitations and suboptimal in vivo delivery systems will require expeditious attention for gene therapy to become a more widely applicable option in cardiovascular diseases including hypertension. However, the elucidation of molecular mechanisms of transcriptional activation of several important genes in the cardiovascular physiology enables us to develop clinical application of gene therapy for hypertension at the level of transcription factors. Recent studies showed that in vivo or ex vivo transfection of double-stranded oligodeoxynucleotides to block the binding of nuclear factors to specific cis-elements in the promoter regions of several genes resulted in inhibition of gene trans-activation and suppressed pathological changes in the cardiovascular system. PMID- 11197850 TI - [Molecular mechanism of hyperlipidemia and future aspects on the therapy]. AB - Elucidating the mechanism of the onset of atherosclerosis is indispensable to understanding the significance of treatment of hyperlipidemia. Atherosclerotic lesions can be characterized as accumulations of cholesterol esters and pathologic reactions by various cell groups. Plasma lipid abnormalities such as hypercholesterolemia, hypertriglyceridemia, and low HDL cholesterol are known as important risk factors for atherosclerotic diseases. The purpose of treating plasma lipid abnormalities is to prevent or treat atherosclerosis. Future studies are required for the development of a powerful therapy for hyperlipidemia by understanding the molecular basis of polygenic hyperlipidemia which is most commonly observed in advanced countries. PMID- 11197851 TI - [Perspectives of post-genomic medical care in osteoporosis]. AB - Osteoporosis is a multifactorial disease for which genetic and environmental factors are determinants. Recently, polymorphisms of many bone metabolism-related genes have been examined in the association study with bone mineral density and fracture incidence. Some showed significant correlation and others not. In addition, genome-wide QTL analysis was done using genome-wide random markers and showed some hot loci. However, the statistical power of each gene and locus are low and the genes to determine human bone mineral density have not been obtained. The accumulating information of genome science will help understand the pathogenesis of osteoporosis and find the useful ways for the prevention and the treatment of this disease. PMID- 11197852 TI - [Post-genome challenges against inflammatory bowel diseases]. AB - Advancement of genome analysis might give great impact to the treatment of inflammatory bowel diseases(IBD). IBD patients are treated by sulfadrugs, steroids and anti-immune drugs. For difficult cases, leukocytapheresis, beclomethasone dipropionate, anti-TNF therapy, anti-LTB4 therapy and other new methods are applied. Developing epoch-making drugs will be achieved by finding new molecular targets. Histologic identification of dysplasia is important in the surveillance of long-standing ulcerative colitis. The molecular diagnosis is required for the distinction of dysplasia from the regenerative inflammatory changes. P53 immunostaining have been proved useful. Various molecular targets will be taken into discussion as additional procedures. Recent genome analysis have revealed some genetic factors contribute to pathogenesis of IBD, which are HLA, IL4, MUC3, IBD1 locus, IBD2 locus and so on. More information about genes concerning IBD will be provided by analyzing dense SNP map using DNA tip. They will open the way to the tailored therapy. PMID- 11197853 TI - [Ethical issues in relation to genetic analysis research]. AB - On April 2000, the so-called Millennium project which was launched by Japanese Government has started. Genetic research is one of the important subject in this project. Since there has been no official guideline for ethical issues in relation to genetic analysis research, Ministry of Health and Welfare arranged a special committee to prepare such a guideline. The process and key points of this guideline which has been published on April 2000 by Ministry of Health and Welfare was described. PMID- 11197855 TI - [Perspectives on postgenome medicine: Neurological disorders]. AB - Aims of scientific research on post-human genome(post-genome sequence) era would be analysis of molecular structure and function of gene products, analysis of particular phenomenon of higher organisms, and development of the way of treatment and prevention of human diseases. Particularly, in the research field of neuroscience and neurological disorders, the progress of human molecular genetics would greatly facilitate the elucidation of molecular pathophysiology of the neurological disorders and finally develop molecular therapy for the diseases. In molecular therapy, fundamental technique of gene therapy should be combined with stem cell-based cell transplantation and new drug design based of scientific evidence. PMID- 11197856 TI - [Tailor-made drug therapy]. AB - Progress in the field of pharmacogenetics has revealed that the phenotypically different responses of patients to drugs are genetically determined by the polymorphisms in the genes involved in their pharmacokinetics and pharmacodynamics. Information on genetic polymorphisms, including single nucleotide polymorphisms, found in the genes encoding drug-metabolizing enzymes, drug transporters, drug receptors, and so on, are now applicable to tailor made(individualized) drug therapy. This report presents the current status of pharmacogenetic approaches to the individualized therapy. PMID- 11197854 TI - [Life style-related disease]. AB - Diabetes mellitus, hyperlipidemia, hypertension and atherosclerotic diseases have recently defined as typical life style-related diseases. A common background of these life style-related diseases is overnutrition and its consequence, obesity. Recent advances in the biology of adipose tissue have revealed that adipose is not simply an energy storage organ but it also secretes a variety of molecules which affect the metabolism of the whole body. Through a systematic search of active genes in adipose tissue, we found that adipose tissue, especially visceral fat expressed numerous genes for secretory proteins. Among them, plasminogen activator inhibitor-1(PAI-1) was over expressed in the visceral fat in an animal model of obesity. Plasma level of PAI-1 was closely correlated with visceral adiposity in human. Thus, PAI-1 secreted from visceral fat may play an important role in vascular disease in visceral obesity. Adiponectin, a novel adipose specific gene product, is abundantly presented in human plasma. This molecule has been shown to have protective roles against atherosclerotic vascular changes and its plasma level is negatively correlated with visceral adiposity. In conclusion, dysregulated secretion of these adipose-specific secretory proteins(adipocytokines) may have important roles in the development of life style-related diseases, especially atherosclerotic diseases. PMID- 11197857 TI - [Progress in targeted gene repair]. PMID- 11197858 TI - [Perspectives on postgenome medicine: Cancer]. AB - Carcinogenesis is a multistep process which is the outcome of the accumulation of genetic and epigenetic events. However, characteristics of cancers, such as drug sensitivity, abilities in invasion and metastasis, are different in each patients, and reliable prediction of those characteristics is not available. DNA microarray and SNP have become the most widely used functional genomics tools. Microarray technology has provided the ability to analyse the expression profiles for thousands of genes, and a wealth of new information that should aid in cancer diagnosis and ultimately in therapy. The SNP project also will generate very variable resources for cancer therapy. The medicine in the next century will be so called 'personalized medicine' based on the new information of patients and diseases. PMID- 11197859 TI - [Perspectives on postgenome medicine: Inborn error of metabolism]. AB - The news that human DNA structure will be completely analyzed in very near future does not mean the whole human genomes being clarified including own function and interaction between each gene. Concerning the diseases of inborn error of metabolism, we should clarify the implication of mutant gene, especially on non cording regions, and genotype and phenotype relationship in each disease. Additional factors producing different phenotypes, even the same mutant gene being involved, such as environmental factors, modifier genes and SNPs in the affected gene are also the project of further discussion. Such information will be most useful for genetic counseling, and treatment and prevention of the diseases. New drugs designed by unique idea, gene therapy and therapy using hES cells should be developed for clinical practice, and for this purpose, fundamental research is indispensable. PMID- 11197860 TI - [Gene therapy for arteriosclerotic diseases]. AB - Recent progress in molecular biology gives us gene therapy, as a new strategy for treatment of cardiovascular diseases. Targeted diseases have been wide-spread from single gene-deficient diseases to more complexed adult diseases such as restenosis after angioplasty and ischemic diseases. Clinical gene therapy for restenosis and angina using VEGF gene have already performed in USA and they can show beneficial effects of such strategies. On the other hand, we have just started a clinical trial using E2F decoy for restenosis after PTA or PTCA, since April 2000. E2F decoy is expected to become a new treatment for restenosis as a gene therapy. Also, the feasibility of a novel therapeutic strategy using angiogenic growth factors such as VEGF to augment collateral artery development has recently entered the realm of treatment of ischemic diseases. We focus on HGF, which is a novel endothelial growth factor. HGF-based therapeutic angiogenesis would possibly result a new treatment for severe ischemic diseases. PMID- 11197861 TI - [A model for clinical study based on genome science--trials in disorders of the immune system and allergies]. AB - Disorders of the immune system, such as allergies, have multi-factorial etiologies that include both genetic and environmental components. The recent advances in genome science have facilitated two strategies for studying the genetic basis of disease: (1) systematic analysis of gene expression profiles and (2) comprehensive analysis of gene variations, such as polymorphisms. Here, we describe a unique research institute, Genox Research Inc., that can relate the clinical profile of a patient to genotyping and molecular profiling. Systematic gene expression analyses using differential display have been performed to explore genes related to allergy, and revealed 93 differentially expressed candidate genes in T-cells. Also, a single nucleotide polymorphism(SNP) analysis project has been designed to mine disease-related and/or drug-response-related genes involved in allergic disorders using biochip technologies. As exemplified above, clinical studies based on these applications of genome science would be of considerable value in clarifying our understanding of multi-gene disorders. PMID- 11197862 TI - [Perspectives on postgenome medicine: Hematological diseases]. AB - With advances in DNA chip(DNA microarray) technology, it has become possible to obtain genome-wide gene-expression profiling. This novel technology is now applied to the study of molecular pathogenesis, differential diagnosis, and prediction of prognosis in the field of hematological malignancies. Importantly, the list of informative genes includes new markers of diseases, which will be utilized for further investigation. As for clinical gene therapy, it has been criticized for promising too much and providing too little during the last 10 years. In 1999, however, the success of hematopoietic stem cell gene therapy was reported in the patients with X-SCID(X-linked severe combined immunodeficiency). The gene therapy of hemophilia B using AAV(adeno-associated virus) vector has also successfully started. Genetic manipulation will be applied to the treatment of various diseases with the development of novel technologies. PMID- 11197863 TI - [Gene therapy and tissue engineering in nephrology and renal transplantation]. AB - Human genome project will be completed in 2003 and we will soon obtain the information of the whole DNA sequence of the human genome. This should affect the therapy of progressive renal diseases since we have no effective remedy to cure the renal diseases. Gene therapy, renal engineering and generation of new drug can be achieved by using the information of human genome. In this context, we described our recent endeavors concerning the gene therapy of transplant kidney, seeking the renal stem cells and reprogramming factors, and exploring genes related to renal fibrosis. Completion of bioinformatics, can facilitate the above post-genome project. PMID- 11197864 TI - [Perspectives on postgenome medicine in the 21st century]. AB - Since the human genome project has been almost completed in 2000, the year of 2001 is the first year of the postgenomic era. A variety of postgenome studies will be done in the next decade, including functional, comparative and structural genomics. These studies may open new area in medicine, because disease susceptibility and drug metabolism would be predicted from genetic characteristics of individuals. Genome studies may also shed a light on cell biology, brain research and regeneration medicine and promote these studies. Bioinformatics will become a basis of postgenome biology and medicine. PMID- 11197865 TI - [Gene therapy for adenosine deaminase (ADA) deficiency: review of the past, the present and the future]. AB - ADA deficiency is the first disease being treated by gene therapy. Since the first trial of gene therapy performed ten years ago, more than 10 patients including our case with ADA deficiency have been treated by the gene therapy with different clinical protocols. In contrast to the recent successful report for X SCID patients, however, no curative effect of gene therapy for ADA deficiency has been achieved at the moment. In this chapter, I would like to review the past, the present and the future of gene therapy for ADA deficiency, and discuss an issue, especially PEG-ADA therapy, regarding the prospect for stem cell gene therapy for the disease. PMID- 11197866 TI - [Perspectives on postgenome medicine: Gene therapy for brain tumors]. AB - Recent development of therapeutic modalities in neurosurgery has brought about dramatic improvement for prognosis of brain tumors. Nevertheless, malignant glioma is one of the most formidable neoplasms in humans. According to a report by the Committee of Brain Tumor Registry of Japan, five-year relative survival rate of malignant gliomas is less than 10%. Malignant gliomas grow aggressively infiltrating into the surrounding normal brain tissue. So that total surgical resection is impossible. The tumors respond to radiation and chemotherapy, however, the efficiency has sustained transiently. The advert of new strategies for the treatment of malignant gliomas has long been awaited. We have developed a cytokine gene therapy for malignant glioma since about 10 years ago. Here, we introduce both suicide gene therapies and immune gene therapies including our case(IFN-beta gene therapy). PMID- 11197867 TI - [Perspectives on postgenome medicine: Gene therapy for lung cancer]. AB - The gene therapy or the immunotherapy targeting specific molecule(s) have just introduced into the clinical field in Japan. The first gene therapy for the human lung cancer is underway; an adenoviral vector harboring wild type p53 gene is intratumorally injected. A cancer immunotherapy using the Cyclophilin B derived peptide is in the phase I clinical trial. As the next generation cancer therapies, a variety of strategies are planned and investigated at the laboratory level. They range from the usage of a new viral vector to the introduction of genes with specific biological functions into the cells. In this article, by reviewing the possible approach, an ideal combination of the future remedies is discussed. PMID- 11197868 TI - [Perspectives on postgenome medicine: Gene therapy for esophageal cancer]. AB - Despite improvements in perioperative treatment and surgical techniques, rapid recurrence led to death of many patients with advanced esophageal cancer. Since surgical resection alone rarely results in long term survival, efforts now are focused on combined multi modality treatment in an attempt to improve local control and eliminate micro metastasis present at time of surgery. We have reported that the importance of alteration of p53 gene in progression and prognosis of esophageal cancer. P53 molecule of solid tumors has been shown to play an important role in the response to DNA damage induced by chemotherapeutic agents and radiation therapy, including induction of apoptosis. Based on the research of p53 gene therapy for esophageal cancer, we applied clinical study in 1997. After intensive reference, phase study was accepted in May, 2000. Phase I/II study will start on October 2000. PMID- 11197869 TI - [Gastric cancer--novel strategy of gene therapy for gastric cancer]. AB - Recently stage-oriented treatment for gastric cancer has been done in Japan. Endoscopic mucosal resection for intramucosal cancer and wedge resection under laparoscopy for minimal invasive cancer in the stomach have been performed. For advanced gastric cancer, extended lymph node dissection(D2) has been applied as standard treatment in Japan. However, new strategy has been required for advanced gastric cancer with distant lymph node metastasis and/or peritoneal dissemination. It is well known that gene therapy for cancer has limitation of efficacy, but we believe the new strategy will be available in post-genome era for gastric cancer treatment using 1. developing novel adenovirus, 2. usage of drug delivery system and 3. effective treatment for adverse effect. PMID- 11197870 TI - [Gene therapy for colorectal cancer]. AB - Gene therapy represents a novel approach to the treatment of colorectal cancer, and this brief review addresses the current strategies and ongoing clinical trials, including tumor suppressor gene replacement therapy with wild-type p53, virus-directed enzyme-prodrug therapy and immunomodulatory approaches. All of the clinical trials have been phase I, principally designed to evaluate safety, but some of them provided the evidence of gene delivery and expression. Although the results of pre-clinical studies have been encouraging, clinical trials have not yet demonstrated anti-tumor effect. Gene therapy for colorectal cancer is still in the early stages of development, and fundamental research in the molecular and cellular biology will improve the therapy. PMID- 11197871 TI - [Development of gene therapy for pancreatic cancer]. AB - In order to develop the new therapeutic intervention for pancreatic cancer, we have examined the effect of gene therapy for this miserable pancreatic disease. The transfection of UPRT, a 5-FU converting enzyme, gene resulted in the significant change in sensitivity of pancreatic cancer cells against 5-FU. Anti angiogenesis gene therapy has been also demonstrated to be a promising strategy for pancreatic cancer. It has been revealed that replication-competent adenoviruses are not only the strong weapon themselves but also useful carriers of genes possessing anti-tumor activities as virus vectors specific to tumors without normal p53 function nor intact Rb pathway. Whether these experimental results are universally true require the clinical trials in future. PMID- 11197872 TI - Reminiscence therapy using odor in alcohol-dependent patients- psychophysiological evaluation and psychological evaluation; power spectral analysis of heart rate variability. AB - OBJECTIVE: This research was based on the hypothesis that when alcohol-dependent patients describe themselves, awakening of emotion by affirmative odor stimulation may facilitate memory reframing focusing on more affirmative emotion and memories. To prove the hypothesis, physiological changes accompanied by emotional awakening were evaluated by measuring the autonomic activity. In addition, subjective evaluation by a self-report manner was examined to investigate the effectiveness of Reminiscence Therapy (RT) using odor in alcohol dependent patients. SUBJECTS: Thirty-four patients who met the DSM-IV criteria of alcohol-related disorders and were hospitalized in a ward specialized to alcohol dependence therapy. METHODS: Each patient underwent a one-to-one interview twice. For counterbalance, one interview was performed with odor stimulation using an odor with a relaxing effect that recall pleasant emotion, and the other was without odor stimulation. As the evaluation indices of physiological changes accompanied by emotional awakening, index of autonomic function (HRV; Heart rate variability) for objective evaluation and psychological indices (STAI; State Trait Anxiety Inventory VAS; Visual Analog Scale) for subjective evaluation were measured. RESULTS: 1) Objective evaluation: Regarding the evaluation index of the autonomic function, the sympathetic nervous system activity (LF/HF; low frequency component/high frequency component ratio) was significantly inhibited by odor stimulation (p < 0.05). 2) Subjective evaluation: Compared to the state prior to interview, state anxiety judged by STAI was significantly decreased after interview (p < 0.01). The VAS score was significantly decreased after interview regardless of the presence or absence of odor stimulation (p < 0.0001). CONCLUSIONS: A reduction in state anxiety was observed. The effect of odor was not significant on the subjective evaluation, but the objective evaluation suggested that the odor inhibited the sympathetic nervous system. Thus, it was suggested that odor can be used in RT, that is, emotional changes due to stimulation of odor may be applicable in RT. PMID- 11197873 TI - The Japanese version of Substance Abuse Subtle Screening Inventory and its psychometric assessment. AB - OBJECTIVE: The purpose of our study was the development of the Japanese version of the Substance Abuse Subtle Screening Inventory (SASSI) and its psychometric assessment. METHOD: We translated SASSI-3 into Japanese and refined it through a back-translation technique and focus group approach. Study 1 was a preliminary study to examine the internal consistency and discriminant function of subscales, sensitivity and specificity of the Japanese version SASSI-3 (SASSI-3J). The participants were 20 drug-dependent individuals and 23 non-dependent comparison individuals. Study 2 comprised three parts. The participants were university students recruited from three classes. The first part examined the internal consistency of subscales and the relationship between the subscale Face Valid Alcohol (FVA) and the Kurihama Alcoholism Screening Test (KAST) with 269 students. The second part examined the 2-week test-retest reliability with 51 students. The third part examined the robustness of SASSI-3J against response distortion with 65 students: participants completed the SASSI-3J under standard instructions, under instructions to minimize any alcohol problems they might have (fake good), and under instructions to exaggerate any alcohol problems they might have (fake bad). They also completed the Social Desirability Scale. RESULTS: 1) SASSI-3J showed relatively high sensitivity and specificity when only the Risk Prediction Scales were used or when Rule 9 was excluded from the decision tree; 2) The Risk Prediction Scales of SASSI-3J had high internal consistency, and among them, Face Valid Alcohol (FVA) showed moderately high concurrent validity with the KAST; 3) In both Study 1 and Study 2, the internal consistencies of OAT, SAT, DEF and SAM were moderate to low (0.05 to 0.57). This may not interfere with the subscales' discriminant power but does deny sufficient uni-dimensionality of these scales; 4) SASSI-3J clinical scale scores were shown to be robust against faking good/social desirability bias. PMID- 11197874 TI - Stress-related behavioral alterations accompanying cocaine toxicity: the effects of mixed opioid drugs. AB - The present study evaluated the effects of mixed opioid drugs on the severity of cocaine (COCA) toxicity by examining stress-related behavioral alterations in mice. In order to ascertain the strength of the stress, the continuous observation of the behavioral symptoms in the cage and the forced swimming test (Porsolt test) were performed in the COCA (75 mg/kg, i.p.)-treated groups, with or without the mixed mu-kappa receptor-related opioid drugs, buprenorphine (BUP) and pentazocine (PEN). Using the high-sensitivity activity measuring instrument Supermex, both the spontaneous behaviors in the cage and the forced swimming behaviors in the water were assessed as activity counts. The behavioral alterations in the COCA-treated groups were compared with a group of mice given a 10 min immobilization stress (IM group). In the COCA-only group, a prolonged increase in the spontaneous behaviors accompanied by convulsive seizures was observed even in the surviving mice, unlike in the IM group. However, an acceleration of behavioral despair in the Porsolt test similar to that observed in the IM group was observed in the COCA group after the disappearance of the acute toxic symptoms (5 hours after the COCA treatment). Among the opioid-treated groups, the mortality rate was attenuated only in the COCA-BUP (0.25 mg/kg, i.p.) group. In the COCA-BUP group, a prolonged suppression of the morbid hyperactivity in the cage except for the convulsive seizures, and a normalization of the swimming behavior in the Porsolt test were observed in the survivors. On the other hand, in the COCA-PEN (5 mg/kg, i.p.) group, the swimming behavior in the Porsolt test was abnormally increased in addition to the prolonged morbid hyperactivity in the cage. Therefore, the COCA-induced stress-related behaviors were normalized in the group of mice treated with BUP, a group with a good prognosis. PMID- 11197875 TI - A study on the socio-psychiatric aspects of short-term ARP (Alcohol Rehabilitation Program). AB - The duration of the majority of Alcohol Rehabilitation Programs (ARP) at major hospitals specializing in this treatment is three months. Recently, however, because of diverse backgrounds and patients needs, long periods of hospitalization have become difficult. In response to this, Okamotodai Hospital initiated a one-month ARP program three years ago. One feature of this program is that it can be freely structured to meet the requirements of individual patients. This study compares the prognosis of patients treated under this one-month program with that of those who have undergone the three-month program. A group of 56 patients who had completed a one-month ARP program during a period of two to three years was compared with a group of 46 patients who had completed a three month program over a similar period. The backgrounds of the subjects were researched by questionnaire. A comparison of the prognosis of patients in the respective programs showed there was no statistical difference, with a recovery rate of 45% for both programs. Results of this study statistical difference, with a recovery rate of 45% for both programs. Results of this study cannot be generalized, due to the lack of subjects and recovery of questionnaires. Since enforcement of the one-month ARP, increasing number of patients have been using the program. This fact doesn't necessarily show that the use of ARP improve, although the possibility remains that utilization of the one-month ARP is promoted. In recent years, utilization of brief intervention has been demonstrated and recovery from alcoholism in the outpatient clinics reported. Considering such things, results of the study show that the one-month ARP is a valid and effective program. PMID- 11197876 TI - [Theophylline]. PMID- 11197878 TI - [Behavior of indoor air pollutants]. PMID- 11197877 TI - [Pediatric allergy]. PMID- 11197879 TI - [Japanese cedar pollinosis in infants in the allergy clinic]. AB - Recently, the number of patients with Japanese cedar (Cryptomeria japonica) pollinosis has increased, especially in children. However, little is known about the incidence in infants. We studied on the rate of sensitization and the onset of pollinosis in children under 6 years old. The percentage of positive CAP-RAST to Japanese cedar pollen was 27.6%, in 76 infants (51 male and 25 female, 2 months-5 years old) who visited National Mie Hospital pediatric allergy clinic due to bronchial asthma and/or atopic dermatitis. The youngest child who has been sensitized to pollen was 1 year 8 month old boy. The percentage of positive rate of CAP-RAST to house dust mite was 61.8%. Twenty-seven infants (20 male and 7 female, 2-5 years of age) were diagnosed as Japanese cedar pollinosis in National Mie Hospital Otorhinolaryngology clinic in 1999 and 2000. The youngest child with pollinosis was 2 year 5 month old boy. Most of the 27 infants complained of rhinorrhea and/or eye symptoms and some of them complained cough, snoring, or epistaxis. About 40% were sensitized to Japanese cedar and/or cupressaceae pollen alone, 60% were also sensitized to house dust mite. In conclusion, it is possible that the sensitization to Japanese cedar pollen occurs after 2 season of pollen exposure and pollinosis occurs in 2 years old. Japanese cedar pollen has been an important allergen not only in school children, but also in infants. PMID- 11197880 TI - [Intestinal flora of infants with cow milk hypersensitivity fed on casein hydrolyzed formula supplemented raffinose]. AB - We studied the intestinal flora of infants with cow milk hypersensitivity fed on casein-hydrolyzed formula (MA-1) and the influence of that supplemented with Raffinose (MA-1[R]). Infants with cow milk hypersensitivity were fed with MA-1 for 2 weeks, after which the formula was changed to MA-1[R]. Fourteen subjects were enrolled in this study and divided into two groups; three who fed with breast or conventional milk in addition to MA-1 or MA-1[R](BM group) and 11 mainly fed with MA-1 or MA-1[R] (TF group). Intestinal flora was investigated at two weeks after MA-1 feeding and at two weeks after MA-1[R] feeding, respectively. Bifidobacterium was detected as the most predominant bacteria in all examples in the BM group, and that count and the ratio in all bacteria remained high even after changing MA-1 to MA-1[R]. On the other hand, bacteria count and ratios of Bifidobacterium in all bacteria were conspicuously low in the TF group as compared with the BM group. And with the change from MA-1 to MA-1[R] in the TF group, the bacterial number and the occupation ratio of Bifidobacterium were increased, and Enterobacteriaceae bacterial count and the occupation ratio were decreased. The change of the intestinal flora with MA-1[R] feeding was mainly caused by the breeding action of Raffinose on bifidobacteria. Further studies are needed from a viewpoint of clinical effectiveness about the influence of normalization of the intestinal flora for the treatment of food hypersensitivity. PMID- 11197881 TI - [An electron microscopic study of the relation between epithelial cell damage and eosinophilia in the nasal mucosa of patients with nasal allergy]. AB - To determine the relationship between epithelial damage and eosinophilia in the nasal mucosa of patients with nasal allergy, we examined the nasal mucosa (obtained by surgery) from 74 patients with allergic rhinitis, using light and electron microscopy. The extent of eosinophilia correlated significantly to grades of epithelial damage and torn tight junctions of the epithelial cells. No significant relationships were found between the severity of nasal symptoms and the extents of eosinophilia or grades of torn tight junctions of the epithelial cells. More than 50% specific granules in eosinophils in the allergic nasal mucosa showed normal findings. There were no significant relationships between the extent of eosinophil degranulation and grades of epithelial damage. Based on our results, the release of tubular vesicular structures from the eosinophil granule may be one form of eosinophil degranulation in the nasal mucosa of patients with nasal allergy. PMID- 11197882 TI - [The effect of suplatast tosilate on immunological parameters for the patients with atopic dermatitis]. AB - A dose of 300 mg/day of suplatast tosilate was administered to one hundred one cases of atopic dermatitis for eight weeks, and the severity scores, peripheral blood eosinophil count, total serum IgE levels, plasma eosinophil cationic protein (ECP) levels, and other immunological parameters before and after the trial were observed and comparatively examined. The results are as follows: 1) Temporary improvements were found in the scores of severity and itchiness on all evaluated skin regions (face, limbs, and trunk). These scores decreased significantly for all observation periods at two, four, six and eight weeks after administration of suplatast tosilate compared with those before the administration (p < 0.01). 2) There was no sign of adverse effects on the drug. In the blood tests, one patient displayed elevated levels of GPT and another showed elevated total bilirubin. In the urine test (qualitative test), one case with positive urinary protein was observed. 3) Clinical examinations including assessment of the immunologic parameters were conducted at an average of 8.68 +/- 0.36th week. The peripheral blood eosinophil count, the percentage of eosinophil, and plasma ECP levels significantly diminished compared with those before administration, but no significant difference was found in total serum IgE levels and LDH levels. 4) The subjects were divided into two groups, one in which the clinical scores were improved by more than five and another with scores of less than five (including worsening), and the fluctuation of the immunological parameters (values before and after administration of the drug) of the two groups were compared. As a result, a significant difference was observed in the plasma ECP levels (p = 0.02) and peripheral blood eosinophil count (p = 0.091), but no difference was observed in total serum IgE levels and LDH levels. From the above mentioned results, the high efficacy and safety of suplatast tosilate in the treatment of severe atopic dermatitis were confirmed. At the same time, a decrease in the peripheral blood eosinophil count and the serum ECP levels were observed, suggesting the possibility that these values could be used as indices of the severity of atopic dermatitis. PMID- 11197883 TI - [Genetic analysis of two patients with adenosine deaminase (ADA)-deficiency: detection of three novel mutations and characterization of two paradoxical carriers]. AB - Genetic basis of two patients (AT, MT) with ADA deficiency was studied. We identified three novel mutations (119 Q-->Stop, 235 R-->Q, one base deletion in Exon 4) from the patients. 119 Q-->Stop was detected in AT and her father. Deletion of one base in Exon 4 which would change the reading frame after codon 105 H, was detected in MT, her father and brother. There was no relation between the two families, however, 235 R-->Q was also detected in both the patients and their mothers. Extremely low ADA activity of PBMCs was revealed in healthy MT's mother and brother just as MT, although their dAXP levels of RBCs showed significantly lower than that of MT. We defined that they shared an additional mutation (310 M-->T) together with the mutation described above, respectively. EBV-transformed B-cell line (EBV-B) were established from the carriers. To our surprise, ADA activity of their lines was 1/10-1/5 of normal. The result of heat treatment studies using the EBV-B showed that the mutant ADA rapidly lose its enzyme activity without degradation of the protein. It suggests that 310 M-->T mutant ADA rapidly lost its enzyme activity due to conformational change of the catalytic site of ADA. PMID- 11197885 TI - Increased augmentation index and systolic stress in type 1 diabetes mellitus. PMID- 11197884 TI - [Allergic granulomatous angitis causing ureteral stenosis]. PMID- 11197886 TI - Illustrating the machinery of life. PMID- 11197887 TI - The artistry of Clemente Susini and the La Specola waxes. PMID- 11197888 TI - [Epidemiological and clinical study of West syndrome in Nagasaki Prefecture, Japan]. AB - To determine the occurrence, outcome, and prognostic factors of West syndrome (WS), we performed a retrospective epidemiological study of WS occurred in 47 children (26 boys and 21 girls) in Nagasaki prefecture during a recent 10-year period from 1989 to 1998. The incidence of WS was 3.1/10,000 live births. The mean age at onset of spasm is 6.3 months (range: 2 to 12 months). Thirty-nine patients (83%) had symptomatic WS, in which the prenatal causes (patients) were most frequent, followed by low-birth weight infants (patients), perinatal (patients) and postnatal (patients). The brain CT was performed in 37 patients, and revealed congenital brain malformations (9 patients), destructive brain disorders (12 patients), and no structural abnormalities (16 patients). The seizure outcome was worse in the symptomatic WS than in the cryptogenic WS; seizure/disappeared in 39% of the former and in 75% of the latter/developmental delay before the onset of WS, relapse of WS and persistence of seizures were associated with poor seizure outcomes. Among the remaining seizures at the time of this surveillance, a tonic seizure was most frequently observed, followed by the partial seizures. Lennox-Gastaut syndrome was observed in 2 patients only. Epileptic discharge in the latest interictal EEG were diffuse in 4.3%, focal or multifocal in 60.7%, and absent in 35%, suggesting that many patients with WS had cortical epileptogenic foci. The developmental outcome was very poor in both the symptomatic and cryptogenic WS. The mean DQ in all the patients was 25, and only 4 patients (11%) had a normal DQ (> 75). DQ was lower in patients with congenital brain malformations than in those with destructive brain disorders. PMID- 11197889 TI - [Aims and roles of child neurologists for the 21st century]. PMID- 11197890 TI - [Survey of vaccination for physically-handicapped and epileptic children]. AB - We studied immunization for 128 handicapped patients, from 3 to 15 years of age, in a Seishi Gakuen Hospital, with 8 vaccines: diphtheria-purified acellular pertussis-tetanus combined (DPT), BCG, polio, measles, rubella, mumps, varicella, and Japanese B encephalitis. The rate of vaccination in these patients was lower than in healthy children at 3 years of age in Kanazawa City. There was no significant difference between patients with and without epilepsy. The rate was higher in the hospitalized patients than in the outpatients. More than 90% of the hospitalized patients was immunized against influenza under informed consent in 1997 and 1998. Despite pandemics of influenza in Kanazawa City, where the hospital was located, the period of fever by influenza was significantly shorter in our patients in both 1997 and 1998 than in 1996. Although a half of our patients had epilepsy, they were safely vaccinated with few side effects. PMID- 11197891 TI - [Seizures associated with fever in children of congenital adrenal hyperplasia]. AB - We investigated seizures in 22 children with congenital adrenal hyperplasia (CAH), eight of whom had seizures associated with fever. The follow-up period was 5-18 years. The onset of seizures ranged from 1 to 4 years of age, and the total number of seizures was one to three in all cases. Four cases had seizures twice within 24 hours. None had seizures after 5 years of age. In two of the eight cases, the seizures may have caused by hypoglycemia or hyponatremia, in the remaining six they were considered to be febrile seizures. Three of them had first-degree relatives with febrile seizures. Electroencephalogram was recorded in five cases, with normal results in all of them. One case with febrile status developed localization-related epilepsy later. None showed developmental delay during follow-up. Although seizures in CAH have been ascribed to hypoglycemia and/or metabolic disorders (hyponatremia), our findings implicate unknown factors in the pathogenesis such as excess secretion of corticotropin releasing factor (CRF) under stress, prolonged elevation of CRF during fetus life and linkage between CAH and febrile seizures on the chromosome 6. PMID- 11197892 TI - [Child neurology and neurobiology]. PMID- 11197893 TI - [The developmental effects of an early intervention program for very low birthweight infants]. AB - We assessed the efficacy of an early intervention program (EIP) designed to promote the neonatal behavioral organization and developmental progress in infants born prematurely. The study subjects consisted of 48 very low birthweight infants (< or = 1,500 gms) who received care in NICU of Nagasaki University Hospital, Nagasaki, Japan. During 1993-1996, the experimental group (n = 30) received the NBAS (Neonatal Behavioral Assessment Scale) based intervention combined with a therapeutic program (EIP), for 44 weeks starting from 38 weeks of postmenstrual age. The control group (historical control, n = 18) received the standard medical-nursing care without EIP during 1990-1992. Developmental outcome was assessed in both groups using the NBAS examination after EIP at 44 weeks of postmenstrual age, and the Bayley Scales at 12 months corrected age. Multivariate analyses were performed to adjust for baseline variables that might be associated with the developmental outcome: sex, appropriate or light for dates infant, birthweight, gestational age, Apgar score at 1 minute, duration of intubation, and NBAS cluster score before EIP. In the NBAS examination after EIP, the experimental group achieved significantly higher scores in orientation, motor performance, state range and state regulation tasks than the control group. Furthermore, the experimental group showed significantly higher Bayley Mental and Psychomotor Developmental Indices compared with the control group. These results suggested that EIP was effective in promoting the neonatal neurobehavioral development of very low birthweight infants. PMID- 11197894 TI - [Regional variation in bone mineral density and motor function in children with cerebral palsy]. AB - Bone mineral density (BMD) and motor activity of the upper extremities, were studied in 18 children with spastic cerebral palsy (CP group) and 12 age-matched normal boys (control group). The motor activity was monitored by a piezoelectric transducer. Whole body BMD as well as BMD of the head, upper limbs, ribs, spine, pelvis, and lower limbs was evaluated by dual energy x-ray absorptiometry. In the CP group, BMDs were lower compared to control group in the whole body and in all the body regions (except for the head) especially in the pelvis and lower limbs. BMDs of these regions were higher in walking patients than in bed-ridden, rolling, and crawling patients. Motor activities in the upper extremities were lower in the CP than in the control group. BMD increased with developing motor activity in the upper extremities. These results implicate diminished BMDs of the lower limbs and pelvis, which are associated with standing and walking, to the high incidence of femur fractures in CP. PMID- 11197895 TI - [Teratoma in the cerebellar hemisphere of an infant]. AB - We report here a 4-month-old male infant with a cerebellar teratoma. After vomiting for 5 days, he had a tonic-clonic seizure on the left showing secondary generalization. Neuroimaging studies showed severe hydrocephalus and a large tumor in the left cerebellar hemisphere, which showed calcification. Postictal scalp electroencephalogram showed right hemispheric spikes and spike-waves. He underwent an emergency operation and had the tumor totally removed. Histological diagnosis of the tumor was immature teratoma. Intracranial teratomas have a predilection for supratentorial and midline sites. They are the most common in the neonatal period. We presented a very rare case of teratoma in the cerebellar hemisphere of an infant. PMID- 11197896 TI - [A case of multiple sclerosis with recurrent episodes of psychiatric symptoms]. AB - We reported a 19-year-old woman with multiple sclerosis (MS) with recurrent episodes of psychiatric symptoms at the age of 10 and 19, as the first and 11th relapse, respectively. Her first episode of MS resembled acute encephalitis at the age of 9 and she relapsed 12 times. The psychiatric symptoms were not mood disorders but altered states of consciousness, such as the delirous state. She was treated with high doses of intravenous methylpredonisolone and her symptoms were almost resolved, but her anxiety neurosis remained. Her MRI showed demyelination in the white matter of the frontal lobe and the hippocampus, which suggested that psychiatric symptoms of MS would be related to the frontal lobe lesion. PMID- 11197897 TI - [A case of bilateral coronal craniosynostosis with the P250R mutation in FGFR3 gene]. AB - Recently, the substitution of proline 250 by arginine in the fibroblast growth factor receptor 3 (FGFR3) gene, has been identified in patients with craniosynostosis and defines a new syndrome on a molecular basis. We report a 1 year-1-month-old female with bilateral coronal craniosynostosis who had the P250R mutation in FGFR3 gene detected by DNA sequencing. She had brachycephaly, temporal bossing, high and flat forehead, hypertelorism, mild proptosis, low set ears and no digital abnormalities. She underwent surgical repair at 7 months and her cosmetic problems were improved. Her development was normal up to 13 months of age. DNA analysis from her parents showed that her father had the same mutation. The phenotypes of the P250R mutation in the FGFR3 syndrome are variable even within the same family, but main characteristic clinical features are follows, 1) lateral or bilateral coronal craniosynostosis, 2) mild hand and foot anomalies, and 3) sensory deafness. In FGFR3 syndrome the diagnosis of P250R mutation by polymerase chain reaction (PCR) is very easy and important for early diagnosis and genetic counseling. PMID- 11197898 TI - [Effect of diazepam on apnea attacks in a 6-year-old girl with Rett syndrome: a polysomnographic study]. AB - We reported a 6-year-old girl with Rett syndrome with severe apnea attacks following hyperventilation during wakefulness for which oral diazepam, 1.5 mg per day, showed marked effect. We evaluated the efficacy of diazepam by polysomnography. Polygraphical examinations revealed decrease of apnea attacks from 15.7/hour to 0.6/hour and of the duration of the longest apnea attack from 40 seconds to 18 seconds. These results support the previous reports which suggests involvement of the cerebral cortex and the reticular formation for respiratory disturbance in Rett syndrome. PMID- 11197899 TI - [EEG findings in a case of acute necrotizing encephalopathy of childhood associated with influenza A virus infection]. AB - We reported here a case of symptomatic partial epilepsy following acute necrotizing encephalopathy of childhood associated with influenza A virus infection. This 2-year-old boy underwent repeated EEG recordings, which at the acute stage was dominated by diffuse 1-2 Hz slow waves. The background activity was 5 Hz theta waves on the 49th day. Paroxysmal activities appeared after the 89th day of illness. On the 231st day, EEG showed spike-and-waves on the left and right frontal areas. Interestingly, paroxysmal activities preceded the onset of epileptic seizures by 7 months, and spike-and-waves by 2 months. After 10 months, he had generalized seizures with fever, and partial seizures on awakening without fever. Interictal EEG showed spike-and-waves on the bilateral frontal areas, and diffuse polyspikes and slow waves were occasionally seen. Though the background activity improved, his consciousness level did not recover probably because the thalamus, basal ganglia, brainstem were damaged more severely than the cerebral cortex. PMID- 11197900 TI - [Hopkins syndrome: oral prednisolone was effective for the paralysis]. AB - We describe here a 5-year-old girl who presented flaccid paralysis of the left upper limb after recovery from bronchial asthma. T2-weighted magnetic resonance imaging of the cervical cord revealed a focal high intensity area in the left anterior horn at the C6-C7 level. She was treated with oral prednisolone, and paralysis resolved within two months. Thirty cases of Hopkins syndrome have been reported so far, but its cause remains unknown. Early administration of prednisolone might ameliorate paralysis in this syndrome. PMID- 11197901 TI - [A novel allelic variation of serotonin transporter gene polymorphism in anorexia nervosa]. PMID- 11197902 TI - [Decreased serotonin level in patients with anorexia nervosa]. PMID- 11197903 TI - [Carinal resection of bronchogenic carcinoma]. AB - Carinal resection was performed in 10 cases of bronchogenic carcinoma during 12 year-period. The mean age of patients was 58 years, with a range of 42 to 68 years. There were 7 male and 3 female. The tumor was located on the right side in 7 cases, on the left side in 1 case on the carina in 2 cases. The histological examination showed squamous cell carcinoma in 5 cases, adenocarcinoma in 4 cases and adenoid cystic carcinoma in 1 case. The staging revealed T3N2 M0 Stage IIIA in 2 cases, T4N0M0 Stage IIIB in 1 case, T4N1M0 Stage IIIB in 1 case, T4N2M0 Stage IIIB in 5 cases and T4N3M0 Stage IIIB in 1 case. The surgical methods were as follows; sleeve pneumonectomy in 5 cases, wedge carinal resection with pulmonary resection in 3 cases (right sleeve upper lobectomy in 2 cases and right pneumonectomy in 1 case), carinal resection in 2 cases. The site of bronchial anastomosis was overlapped by thymus in 6 cases. The 30-day mortality rate in tracheo-carinal resection was 10% (one patient). Eight patients died and remaining 2 patients are still alive without any evidence of recurrence. 5-year survival rate was 36%. These outcomes were almost equal to those of surgical case in the same stage. PMID- 11197904 TI - [Successful resection of endotracheal metastatic lung cancer using percutaneous cardiopulmonary support system: a case report]. AB - We experienced a rare case of endotracheal metastasis derived from squamous cell lung cancer. The patient was 56 year-old male whose primary lung cancer of the left upper lobe was completely resected. Pathological diagnosis indicated stage IIB and he underwent two cycles of chemotherapy with CDDP + VDS. He had been asymptomatic thereafter, however, two years postoperative chest CT revealed a nodular lesion of the anterior carinal wall. Bronchofiberoptic examination showed same as CT finding and its brushing cytology confirmed squamous cell carcinoma. WE successfully resected his endotracheal metastatic lesion and reconstructed by direct sutures assisted by PCPS (Percutaneous Cardiopulmonary Support System). His postoperative course was uneventful. Majority of the reported cases of endotracheal metastases were treated conservatively as radiation, laser and/or chemotherapy. We conclude that PCPS is useful device for surgical management for selected cases. PMID- 11197905 TI - [New approaches for excellent operative field during tracheobronchial anastomoses in sleeve pneumonectomy: cardiopulmonary bypass and diseased lung ventilation]. AB - Cardiopulmonary bypass (CPB) and diseased lung ventilation were presented as new methods of oxygenation during carinal reconstruction. Two cases of left sleeve pneumonectomy (SP) were performed for bronchial gland carcinoma through clamshell incisions. Adequate oxygenation and excellent operative fields were provided by CPB in both patients. The postoperative courses of these patients were uneventful, although they developed temporary pulmonary edema that needed mechanical ventilation and appropriate diuretics for several days. One case of patient with squamous cell carcinoma after chemotherapy was successfully treated by right SP through midline sternotomy. Adequate oxygenation and excellent operative fields was obtained by diseased right lung ventilation in this patient. The postoperative course of the patient was uneventful without mechanical ventilation support. These procedures of oxygenation in this paper are considered to be safe and effective methods for carinal reconstruction. PMID- 11197906 TI - [A case of adenoid cystic carcinoma of the left main bronchus, which was performed carinal resection and reconstruction while the aortic arch is pulled down]. AB - A 55-year-old woman, who had treated as bronchial asthma for eight months, was admitted to our hospital. Chest CT scan showed a mass in the left main bronchus. Bronchoscopic examination revealed a tumor obstructing the left main bronchus and invading the left lower portion of the trachea. The pathologic diagnosis was adenoid cystic carcinoma. Primary resection of the left main bronchus and the carina with the objective and one-stoma-type carinal reconstruction were performed by the left thoracotomy. We pulled down the aortic arch to obtain an operative field, and carried out the operative procedure at the upper side of the aortic arch. As the resection margin contained residual tumor, the postoperative irradiation (50 Gy) was added. PMID- 11197907 TI - [Carinal resection for lung cancer]. AB - Between January 1993 and March 2000, 16 patients underwent carinal resection for lung cancer; primary carcinoma in 15 patients and recurrent disease in 1. Age ranged from 41 to 74 years old, and the mean age was 58 years. Sleeve pneumonectomy was performed in 8 patients, right upper sleeve lobectomy in 7, and only carinal resection for the recurrent lesion in 1 patient. Combined resection of the aorta was performed in 2 patients, superior vena cava, in 5, left atrium and esophageal wall, in 1, and panpleura, in 1. The 30-day mortality rate was 25.0% (4/16) and the morbidity rate was 50% (8/16). The causes of death were pneumonia, airway bleeding without vascular fistula, brain edema and acute cardiac failure. Anastomotic complication including tracheo-pulmonary vascular fistula and stricture occurred in 2 patients. The 5-year survival rate was 23%. PMID- 11197908 TI - [Carinal reconstruction with wide airway resection by a new technique]. AB - Carinal reconstruction with wide airway resection by a new technique was conducted in two cases. A 61-year man with tracheal stenosis by tracheal cancer, 6 tracheal rings, 2 left bronchial rings, total right main bronchus, for which carina was resected and reconstructed by a new technique and for a 69 year man with lung cancer in right upper lobe, for which right upper-middle bilobectomy, S6 segmental resection and circumferential pulmonary artery resection were performed. The tracea, left main bronchus, and right basal segment bronchus were anastomosed by new technique and the right main pulmonary artery and basal segment artery was anastomosed subsequent to chemotherapy. Both patients discharged within seventeen postoperative days in consideration of the absence of postoperative complication. Bronchoscopic findings after reconstruction indicated neither stenosis nor dehiscence at the site of anastomosis. The new reconstructive method of carina permits simple anastomosis, the possibility of carina reconstruction even in the case of wide airway resection and loss tension at the site of anastomosis. PMID- 11197909 TI - [Carinal resection for bronchogenic carcinoma]. AB - The purpose of this study was to evaluate the results of carinal resection for bronchogenic carcinoma in our institute. From 1981 to 1999, 24 carinal resection were performed for squamous cell carcinoma (n = 19), adenoid cystic carcinoma (n = 2), small cell carcinoma (n = 1), adenocarcinoma (n = 1), and mucoepidermoid carcinoma (n = 1). Nineteen underwent sleeve pneumonectomy, 2 had carinal resection without lung resection, 2 had carinal resection with right middle and lower lobectomy, and 1 had wedge pneumonectomy. In the patients with sleeve or wedge pneumonectomy, there were 5 operative death and 3 patients had survived for more than 3 years. Two patients with low-grade malignant tumors underwent carinal resection without lung resection and survived more than 10 years. We believe that limited carinal resection for low-grade malignant tumors are safe and valuable procedure. Careful selection of patients with sleeve or wedge pneumonectomy is mandatory. PMID- 11197910 TI - [Results of carinal resection for primary lung cancer]. AB - Carinal resection for primary lung cancer was clinical evaluated. Carinal resection was performed in 18 patients. Thirteen patients underwent carinal resection and the other 5 sleeve or wedge pneumonectomy. The carinal reconstruction was of montage type in 10 patients and the double-barrel type in 2. There were 2 operative deaths, postoperative mortality rate was 11.1%. The 5 year survival for 16 patients excluding the 2 operative deaths was 38.8%. The 5 year survivals were 41.7% and 21.4% for N0 and N2 disease, respectively. Selected patients with localized lesion without mediastinal lymph node metastasis are the candidate for carinal resection and reconstruction. PMID- 11197911 TI - [Aortic root replacement after operation for the ascending aorta and/or aortic valve]. AB - We reviewed ten cases who underwent aortic root replacement after operation for the ascending aorta and/or aortic valve. As initial operation, aortic valve replacement (AVR) was performed in five patients, replacement of the ascending aorta in two, original Bentall operation in two, and entry closure and suspension of the aortic valve in one. At reoperation, three patients were diagnosed as aneurysm of the ascending aorta, two were annulo-aortic ectasia, and one was acute aortic dissection, chronic dissecting aneusym, pseudoaneurysm of the ascending aorta, prosthetic valve endocarditis, and massive aortic regurgitation. Aortic root replacement was performed using mechanical valved composite graft in all cases. One patient who underwent repeat aortic root replacement for prosthetic valve endocarditis was died of septemia and ventricular fibrillation. Five patients had nine complications (two low output syndrome, respiratory failure and cerebral infarction, one gastrointestinal bleeding, septemia and ventricular fibrillation). In conclusion, aortic root replacement after operation for the ascending aorta and/or aortic valve was performed with acceptable morbidity and mortality. PMID- 11197912 TI - [A case of surgical treatment for cardiac tamponade caused by a ruptured coronary aneurysm accompanied by a coronary artery-pulmonary artery fistula]. AB - A 67-year-old woman experienced a sudden severe pain in the area of her left shoulder and back. Three days later the pain recurred, after which she fell into shock and was taken to another hospital by ambulance. A plain chest CT scan showed a cardiac tamponade, while an enhanced chest CT scan demonstrated a coronary aneurysm in the left anterior descending branch draining to the pulmonary artery. Coronary arteriography revealed a saccular type aneurysm, 5 cm in diameter, with a coronary artery-pulmonary artery fistula. After pericardiocentesis, she recovered from her state of shock. The patient was then transferred to our hospital, where she underwent emergency surgery. Under a cardiopulmonary bypass, the stem of the aneurysm and the fistula were ligated and resected. She recovered smoothly and was discharged on the 24th postoperative day. PMID- 11197913 TI - [A case of a left atrial primary malignant fibrous histiocytoma]. AB - Primary malignant fibrous histiocytoma (MFH) of the heart is very rere. We report a case of a primary intracardiac MFH. A 50-year-old woman underwent an operation for congestive heart failure due to left atrial (LA) tumor. Cardiac echocardiogram showed the tumor attached to the septal wall and posterior wall of LA. We extendedly resected the tumor with septal and partially posterior wall and reconstructed there with pericardial substitute. Pathological diagnosis was MFH. Although she did well postoperatively, cardiac echocardiogram showed a recurrent tumor in the LA at 10 days after operation. She developed respiratory failure, and chest and abdominal CT demonstrated metabolism to the lung, liver and bladder at post operative 47 days. At 77 days after operation, she expired. The prognosis of MFH is poor despite surgery. We recommend extended surgery, if the LA tumor had wide base attached to the septal or posterior wall. PMID- 11197914 TI - [A case of lung cancer underwent carinal resection with right upper lobectomy and carinal reconstruction with double-barreled anastomosis]. AB - A 70-year-old male complaining cough was admitted to our hospital. Bronchoscopic examination revealed a tumor mass which occluded the orifice of the right upper lobe. Chest computed tomographic (CT) scans gave the image of tumor invasion at the carina. The pathological diagnosis of the tumor was squamous cell carcinoma. Operation was accomplished by right posterolateral thoracotomy approach through the fifth rib bed. The carinal resection with right upper lobectomy was followed by a double-barreled anastomosis of the right intermediate trunk and left main stem bronchus into the carina. The operation was successfully performed and was considered curative. The length of resected airway measured 4.0 cm from tracheal line of resection to the divided the right intermediate trunk. Reinforcement of the anastomosis was not performed in this case. No postoperative complication occurred but mild ischemia of the anastomosis. The patient died of recurrent tumor in a year and 2 months after operation. PMID- 11197915 TI - [Surgical analysis for N 2 factor in non-small cell lung cancer]. AB - In this study we analyzed 33 cases which underwent complete surgical resection to assess the role of surgery in the treatment of patients with N 2 NSCLC. The 3 year survival rate was 33.3% and the median survival time was 26.1 months. The survival curve for patients with T 3 factor was statistically worse than those with T 1 or T 2 factor. Further, the survival curve for patients with p 2 or p 3 factor was significantly lower than than that for those classified as p 0. Patients classified with p 2 or p 3 had a survival rate under 2 years. Only one patient diagnosed as T 3 achieved 3 year survival. This patient had a pm1 tumor with p 0 factor. We thereby recommend that surgery should only be performed for those N 2 NSCLC patients diagnosed as T 1 or T 2 with a classification of p1 or less. PMID- 11197916 TI - Idiopathic Budd-Chiari syndrome in a patient with homozygous Factor V Leiden and heterozygous Factor II G20210A mutations. PMID- 11197917 TI - Vagus-sparing gastric fundectomy in the rat: development of osteopenia, relationship to urinary phosphate and net acid excretion, serum gastrin and vitamin D. AB - In man and experimental animals, partial and total gastrectomy and gastric vagotomies disturb extracellular mineral homeostasis, osteopenia being among the late outcomes. The sequence of events is complex and insufficiently understood. We report on the long-term effects of gastric fundectomy (FX; FX-1, n=11; sham operated controls, n=14) sparing gastric vagal fibers at the lesser curvature in the rat, a procedure eliminating gastric acid production but preserving gastric reservoir function. After FX-1 there was a marked increase of gastrinemia [FX-1: 590 (SE 95); controls: 82 (5) pg-equiv/ml; P<0.001], serum 1,25-dihydroxyvitamin D [FX-1: 188 (17); controls: 86 (6) pg/ml; P<0.001], phosphaturia [FX-1: 32 (2); controls 23 (2) micromol/h; P<0.001] due to increased fractional phosphate clearance, elevated urinary net acid [FX-1: 21 (2); controls: 16 (1) micromol/h; P=0.03], and low urinary pH. The urinary excretion of hydroxyproline was increased [FX-1: 137 (15); controls: 99 (8) micromol/h; P=0.01], and crosslinks were also high. These changes were associated with a significant decrease of bone ash calcium, magnesium, and phosphorus. Bone histomorphometry revealed signs of high bone turnover. No signs of hyperparathyroidism were detectable. Acute stimulation of serum gastrin by gastric acid abolishing omeprazole failed to provoke extra-osseous changes, as seen in the long-term after fundectomy. It was concluded that the described type of fundectomy disturbs gastrinemia, acid-base and phosphorus metabolism, thereby initiating osteopenia. This animal model may be suitable for research into post-gastrectomy bone disease. PMID- 11197918 TI - Measurement of respiratory impedance by impulse oscillometry--effects of endotracheal tubes. AB - Impulse Oscillometry is a new, noninvasive method to measure respiratory impedance, i.e. airway resistance and reactance at different oscillation frequencies. These parameters are potentially useful for the monitoring of respiratory mechanics in the critically ill patent with respiratory dysfunction. The endotracheal tube, used to mechanically ventilate these patients, however, represents an additional nonlinear impedance that introduces artifacts into the measurements. The objective of this work was therefore to investigate the effects of clinically available endotracheal tubes on resistance and reactance of an in vitro analogue of the respiratory system. Additionally, the effects of decreasing the compressible gas volume in this experimental model, as a simulation of decreased lung capacity and compliance, was investigated. Impulse oscillometric measurements of the test analogue gave highly reproducible results with and without an endotracheal tube. The tubes had significant influence on the measurement of the test object at all frequencies investigated. Changes of low frequent reactance were negligible - at least if repetitive measurements of the same system are performed - for realistic measurement of airway resistance, a correction of the tube impedance or measurement of the pressure distal of the tube is required. Resistance increased and low frequent reactance decreased significantly with decreasing gas volume. These changes were of magnitudes higher than the variations due to the introduction of the endotracheal tubes. Our results suggest that changes of respiratory reactance measured with impulse oscillometry may be used as a monitoring parameter in intubated patients. PMID- 11197919 TI - Wet-to-dry ratio of lung tissue and surfactant outwash after one-lung flooding. AB - Unilateral flooding of the lung after intubation with a double-lumen tube enables intraoperative sonography of the lung tissue. The flooding restricts the pulmonary blood stream of the flooded lung in a relevant degree and thus reduces the right-to-left shunt volume. The deficient perfusion of the lung tissue during the flooded phase might cause capillary permeability disorders and secondary oedema development. This can be determined by examination of extravascular lung water (EVLW) after draining and reventilation of the flooded lung. Although one time unilateral lung flooding must be distinguished from bronchopulmonary lavage, it is interesting to study the effects of flooding on the surfactant system. The wet-to-dry ratio of the lung tissues of 13 female pigs was ascertained at different times following one-lung flooding (1 to 11 weeks). A trend towards an increased wet-to-dry ratio in the previously flooded lung was found only in the tissue samples taken 1 h after reventilation. After only 24 h, the two lungs no longer differed in their wet-to-dry ratio. In six pigs, the phospholipid content of the drained flooding liquid was determined. It was shown that the surfactant loss caused by flooding was maximally 47% of the calculated surfactant pool of the respective lung. PMID- 11197920 TI - Relationship between mast cells/parietal cells and maximal/basal acid output ratio in chronic gastritis. AB - Mast and parietal cells were concomitantly demonstrated in biopsies from corpus mucosa of patients with various forms of chronic gastritis. The ratio of mast/parietal cells and the ratio of maximal and basal acid output were negatively correlated. PMID- 11197921 TI - Protective effects of trimetazidine in transient spinal cord ischemia. AB - The neuroprotective effect of trimetazidine (TMZ) was tested prospectively in a rabbit spinal cord ischemia model. Ischemia was induced by clamping the aorta just distal to the left renal artery and proximal aortic bifurcation for 20 min. Twenty-five male New Zealand white rabbits were randomized as follows: TMZ group (n=100) receiving 3 mg/kg trimetazidine intravenously before the occlusion of the aorta; control group undergoing occlusion but receiving no pharmacologic intervention (n=10); sham-operation group (n=5) subjected to operative dissections without aortic occlusion. Physiological parameters and somatosensory evoked potentials (SEP) were monitored in animals before the ischemia, during the ischemia and in the 1st, 15th and 60th min of reperfusion. Neurologic status was assessed 24 and 48 h after the operation. The spinal cord, abdominal aorta, and its branches were processed for histopathologic examinations 48 h after the operation. At the end of the ischemic period, the average N1-P1 amplitude was reduced to 22% of the baseline in all ischemic animals. This was followed by a gradual return to 90+/-2% of the initial amplitude in the TMZ group and 81+/-2% in the control group (P<0.05) after 60 min of reperfusion. The average motor function score was significantly higher in the TMZ group than the control group (3.7+/-0.5 vs 3.1+/-0.6 at 24 and 3.5+/-0.7 vs 2.9+/-0.6 at 48 h; P<0.05). Histologic observations were clearly correlated with the neurologic findings. The results suggest that trimetazidine reduces spinal cord injury during thoracoabdominal aortic operations and may have therapeutic utility during high risk operations. PMID- 11197922 TI - Leucine and protein metabolism after bilateral nephrectomy in rats: the role of hepatic tissue. AB - The aim of this study was to evaluate the effect of acute uremia on changes in leucine and protein metabolism in the whole body and in hepatic tissue. Acute renal insufficiency was induced by bilateral nephrectomy (BNX). Twenty-four hours later, parameters of protein and amino acid metabolism were evaluated in the whole body using primed constant intravenous infusion of L-[1-14C]leucine, and in isolated perfused liver (IPL) using cx-keto[1-14C]isocaproate. The control group consisted of sham-operated rats. BNX induced a marked decrease in proteolysis, protein synthesis, leucine oxidized fraction and leucine clearance. The decrease in protein synthesis was higher than in proteolysis. A significant drop in protein synthesis was observed in muscle, gut, heart and spleen. The study with IPL in BNX animals showed decreased oxidation of ketoisocaproic acid and higher concentrations of the branched-chain amino acids (BCAA) leucine, isoleucine and valine in perfusion solution. We conclude that the cause of rapid depletion of body proteins after BNX is a greater decrease in protein synthesis than in proteolysis associated with an increase in leucine oxidized fraction. The data obtained in the IPL model indicate that BNX causes metabolic changes that enable resynthesis of BCAA from corresponding branched-chain keto acids in liver. PMID- 11197923 TI - The effect of family intervention on chronic schizophrenics under individual psychosocial treatment: a 3-year study. AB - BACKGROUND: The effectiveness of family intervention in schizophrenia has mainly been tested by controlled trials which recruited patients after hospital discharge. Less is known about its effectiveness when chronic schizophrenics displaying negative rather than positive symptoms are engaged in treatment. This study was conducted in two community-based rehabilitation units for chronic psychiatric patients and was planned to test: (1) whether family intervention combined with individual psychosocial treatment is more effective than individual psychosocial treatment in improving the clinical and social prognosis of schizophrenic patients belonging to high expressed emotion (high-EE) families, and (2) whether family intervention exerts its effect on the patients through the reduction of EE in their families. METHODS: Forty patients from high-EE families, all under neuroleptic medication and in remission at intake, were evenly assigned to individual psychosocial treatment or to psychoeducational family intervention plus individual psychosocial treatment. Individual treatment consisted of vocational and social skills training; family intervention mainly comprised 13 group sessions with relatives. Patients were treated for 12 months and were followed-up for the next 2 years. Measures of clinical outcome comprised relapse, hospitalization and clinical exacerbation. Measures of social outcome included social functioning and role performance. Re-employment served as an additional measure at the follow-up assessments. RESULTS: The experimentals were free of relapses and hospitalizations during the 1st year of follow-up. The difference in relapse rates between experimentals and controls over the same period was statistically significant (P = 0.05), especially if drop-outs were included in the statistical analysis. The difference in hospitalization rates did not yield any statistical significance. All differences declined in the 2nd year of follow up. Family intervention was found to be positively, but not significantly, associated with higher reversal rates from high to low EE, especially among full attenders of relatives' group sessions. High EE was identified as a predictor of relapse, but not of hospitalization, over the 2-year follow-up period. CONCLUSION: Results support the importance of encompassing family members in the community care and tertiary prevention of schizophrenia. PMID- 11197924 TI - Suicidal acts and ideation in homosexual and bisexual young people: a study of prevalence and risk factors. AB - BACKGROUND: Suicide attempts are the most robust clinical predictor of suicide, which is now the second cause of death among young people in many countries. Previous research has shown an increased risk of attempted suicide associated with a homosexual orientation. However, the mechanisms underlying this increased risk are not yet clear. This study therefore aimed to determine the risk of attempted suicide and the effect of potential risk factors on the occurrence of suicidal ideation and behaviour among homosexual youngsters. METHODS: The association between suicidal ideation and behaviour and potential risk factors was assessed by means of a questionnaire in a general population sample of homosexual or bisexual young people and a control sample consisting of school pupils. RESULTS: A twofold increased risk of suicidal ideation was found associated with a homosexual or bisexual orientation. A significantly increased risk of attempted suicide associated with homosexuality or bisexuality was found in females. Independent of sexual orientation, depression was identified as a significant risk factor for suicidal ideation, while suicidal behaviour was associated with low self-esteem, higher levels of hopelessness and suicidal behaviour in someone close. Among homosexual or bisexual young people, less satisfying homosexual friendships were an additional risk factor for suicidal behaviour. CONCLUSIONS: The identified increased risk of suicidal ideation among homosexual or bisexual young people is associated with depression and may lead to suicidal behaviour, independent of sexual orientation, especially in the presence of a role model of suicidal behaviour, and among those with unsatisfying friendships. PMID- 11197925 TI - The social context of insight in schizophrenia. AB - BACKGROUND: Psychiatrists place great weight on impaired insight in schizophrenia, generally attributing it to pathological mental processes. However, denial of illness may be based on attitudes common in patients' social and cultural groups. Moreover, even where denial of illness has a pathological element, it may be affected by the social context. In this paper, we predicted that denial of illness would be associated with social distance between clinician and patient, and reduced by access to 'normalizing' social interaction. METHOD: One hundred and fifty patients with schizophrenia in the London arm of the European Schizophrenia cohort were assessed using the 'Awareness of Illness' (AI) subscale of David's Assessment of Insight. Clinical and social attributes were related to AI. RESULTS: There was little evidence for our social distance hypotheses: there was little variation in AI by social class, ethnicity, membership of a drug taking culture or the presence of strongly held religious beliefs. However, there were strong relations between AI and the size of primary group, consistent with our normalizing hypothesis. CONCLUSIONS: The normalizing function of social support is in line with modern psychological models of delusion formation. Longitudinal data will eventually be available from the current study that will assist in establishing the causal direction of this association. PMID- 11197926 TI - Multiple applications of the GHQ-12 in a general population sample: an investigation of long-term retest effects. AB - BACKGROUND: Previous studies have indicated that the 60-, 30-, 28- and 12-item versions of the General Health Questionnaire (GHQ) are liable to retest effects, especially when administered multiple times with short intervals. The aim of this study was to examine data from a large general population sample for evidence of any retest effects over 7 yearly applications. METHODS: A core panel was drawn from the British Household Panel Survey of those respondents who had completed the GHQ-12 seven times from 1991 to 1997 (n = 4749). The panel results were compared with cross-sectional data from the Health Surveys for England for the same years. The analyses were conducted separately for males and females broken down by age groupings. RESULTS: No evidence of retest effects was found. For males, the panel results did not diverge significantly from the cross-sectional results. For females, the panel results did indicate a divergence from the cross sectional results, but this was due to the age composition of the panel and differing age trajectories. CONCLUSION: The GHQ-12 is a consistent and reliable instrument when used in general population samples with relatively long intervals between applications. PMID- 11197927 TI - Factors associated with immediate dropout of outpatient treatment for drug abuse in Rio de Janeiro. AB - BACKGROUND: The advantage of treatment of drug addiction over no intervention has long been recognized. The high dropout rates that are often reported in outpatient clinics may limit treatment effectiveness. This study aimed to analyze adherence to an outpatient program for drug addicts, mainly cocaine addicts, in Rio de Janeiro, Brazil, and its correlates. METHODS: Of particular interest was immediate dropping out, defined as coming just once to the facility. The data were collected from medical charts and registers of a randomly selected sample of 480 patients. RESULTS: A total of 468 medical records were available for review, and 57% of the patients came just once to the facility. A negative association was found between immediately dropping out and female gender, being white, prescription of medication and use of multiple management resources by the therapist (referral to mutual support groups, social workers, family therapy and medical assessment, even with no prescription). A positive association was found with parental death in childhood, history of mental illness in the family and addiction to alcohol combined with abuse of other illicit substance(s). CONCLUSIONS: The high dropout rates associated with certain treatment approaches strongly indicate opportunities for improving care of drug addicts at that outpatient center. PMID- 11197928 TI - Computerised information systems in English mental health care providers in 1998. AB - BACKGROUND: This study formed part of the background work for the development work of a new Mental Health Minimum Data Set in England. It surveyed the range and nature of information systems currently used by English mental health care provider Trusts. It also surveyed relevant aspects of their organisational arrangements. METHOD: Information was collected by a telephone survey of Trust information and clinical service managers. RESULTS: Most Trusts have a complex array of different information systems--the median number is four. Even where fully integrated systems are in place, these do not necessarily cover all data areas over the whole of the Trust's operations. Sixty-three percent of Trusts use more than one patient numbering system. Sixty-percent have implemented or formally piloted routine collection of outcome scoring, 51% using the Health of the Nation Outcome Scale (HoNOS). A simple model suggested that the proposed data set could realistically be implemented nationally over a 4-year timescale. CONCLUSIONS: Given the current information system context and planned developments it would be realistic to implement the proposed Mental Health Minimum Data Set over a 4-year timescale. PMID- 11197929 TI - A comprehensive clinical database for mental health care in England. AB - BACKGROUND: Monitoring and researching clinical care calls for comprehensive clinical databases. In mental health care these need to cover all aspects of the care of each patient and to accommodate the complexity of care which may last from weeks to years. This paper describes the pilot work for a mental health clinical database intended to be implemented throughout the English National Health Service. METHODS: In collaboration with three pilot sites, a set of data extracts was defined which could reasonably easily be produced, mostly using existing statistical data collection systems. Software was designed to integrate these extracts into patient-based records describing overall spells of mental health care. These data were extracted from their systems for a 6-month pilot period. RESULTS: Two of the three sites produced data sets, which appeared to give a reasonably complete account of the work undertaken in the pilot period. Known differences in service design and clinical perspective between the two sites were clearly reflected. CONCLUSIONS: The approach to extracting and collating the data is workable within existing resources and produces illuminating data for clinical audit, management and planning. Completeness and accuracy of data is likely to be a continuing problem, as for any routine data capture exercise. However, the process of integrating data from several channels assists this, as inconsistencies become apparent and can be tackled. The approach is now being implemented throughout England. PMID- 11197930 TI - [Arthrosis--histology and pathogenetic approaches]. AB - Osteoarthitis is the most common joint disease affecting over 60% of the elderly population. It is characterized by the progressive erosion of articular cartilage leading to incapacity of movement. In the great majority of instances, osteoarthritis appears insidiously, without apparent initiating cause. This primary form is usually oligoarticular involving hip, knee, cervical vertebrae, interphalangeal joints of the fingers or tarsometatarsal joints of the feet. In case of an underlying systemic disease or local injury the cartilage destruction is considered as secondary osteoarthritis. The pathogenesis of primary osteoarthritis suggests an intrinsic disease of cartilage in which biochemical and metabolic alterations result in its breakdown. Within the last decades different models were established which also concentrated on other joint structures such as bone or ligaments. Changes of the subchondral bone were found to precede cartilage damage suggesting a primary alteration of the subchondral region. Other studies concentrated on the metabolic activity of chondrocytes in healthy cartilage of osteoarthritis patients. The precise event that leads to these changes is still not clear. This review concentrates on the histological features in the course of the disease and tries to provide a summary on different pathogenetic concepts. PMID- 11197931 TI - [Arthrosis--a single or many diseases?]. AB - The classical features of osteoarthritis (OA) include osteophytosis, joint space narrowing, subchondral cyst formation, sclerosis, deformity and low-grade synovitis. OA has been tacitly assumed to be a homogeneous disorder and dismissed as "degenerative". This short article will seek to challenge this traditional view and suggest that at least two major processes emerge from detailed radiological studies in patients with OA. One comprises osteophytosis associated with hyaline cartilage thinning and perhaps joint instability. This may represent a normal response to joint instability, and be seen as a healing mechanism. The other, when subchondral sclerosis and bone attrition predominate, may reflect joint failure. PMID- 11197932 TI - [Magnetic resonance tomography (MRI) of joint cartilage. Current status of knowledge and new developments]. AB - MRI is the most accurate noninvasive technique available for assessment of normal articular cartilage and cartilage lesions. MRI cannot only provide morphologic information about the area of damage, but can also provide unique insight into the biochemical composition of the articular cartilage. New image processing techniques such as three-dimensional mapping of cartilage thickness will help to establish automated analysis of cartilage loss. Theses techniques are ideally suited for monitoring patients who undergo treatment with new chondroregenerative drugs. PMID- 11197933 TI - [Pediatric arthroses as a sequelae of enchondral damage. Examples of frostbite, Kashin-Beck disease, rat bites and other etiologies]. AB - PURPOSE: To review the similarities of the radiographic changes in frostbite, the Asian disease of Kashin-Beck, and long term growth damage from injury such as rate bite. MATERIALS AND METHODS: Radiographs and literature from subjects with these diagnoses were analyzed for the common features and differences. Included was an infant with hand changes 8 months after unwitnessed rat bites. RESULTS: Each condition revealed findings consistent with the hypothesis of localized damage to sites of enchondral ossification, including at acrophyses--the growth plates that are not between epiphysis and metaphysis, but instead lie at the margins of growth centers, including carpal and tarsal bones, and the non epiphyseal ends of small tubular bones. DISCUSSION: The patterns observed support a final common pathway of damage in frostbite due to cold injury, Kashin-Beck disease (endemic in China) of unknown etiology, and damage from toxins associated, for example, with rat bite. In frostbite, the distribution is acral because of the site of exposure, while the distribution in Kashin-Beck is more diffuse and often less contiguous. In each condition, arthrotic sequelae may be expected in the natural course of follow-up. MRI may play a role in acute diagnosis that might modify the course of each disease. PMID- 11197934 TI - [Radiologic quantification of joint changes. A methodological overview]. AB - Osteoarthritis as well as rheumatoid arthritis lead to chronical progressive destruction of diseased joints. As aggressive new treatments need to be evaluated, plenty of (semi-) quantitative methods for the radiological joint evaluation had been developed. They lack sufficient reproducibility due to their low objectivity. Modern approaches of computer-assisted radiological quantification should increase the reproducibility and efficiency of radiological scoring. Automatically calculated, computer-assisted measurements of joint space, cartilage- and synovial volume, periarticular assessment of bone mineral density and quantitative analysis of the subchondral plate will have major impact on the radiological routine of the future. PMID- 11197935 TI - [HIRE (high intensity reduction). New cerebrospinal fluid suppressed T2-weighted imaging sequence]. AB - PURPOSE: The HIRE sequence utilizes the very long T2 value of CSF to suppress its high signal contribution in T2-weighted imaging by an image subtraction technique. METHODS: To assess the diagnostic potential of a new dark fluid sequence HIRE (High Intensity REduction) in the diagnostic work-up, 20 patients with histologically confirmed cerebral gliomas were examined with T2-weighted FSE, T1-weighted SE, fast FLAIR and HIRE using identical scan parameters. In patients with enhancing lesions fast FLAIR and HIRE were added to the contrast enhanced T1-weighted SE images. Images were analyzed in a qualitative and quantitative evaluation. In the qualitative lesion analysis, lesion delineation and differentiation between enhancing and non enhancing tumor tissue were by two readers. For the quantitative analysis lesion-to-background and lesion-to-CSF contrast and contrast to noise ratios were determined in an region of interest analysis. RESULTS: HIRE achieved a significant reduction of the CSF signal without loosing the high gray-to-white matter contrast of T2 weighted sequences. In the quantitative analysis, the contrast ratios of the HIRE were lower compared to the FLAIR images due to a relative high background and CSF signal. After the application of contrast media HIRE images revealed a significant signal increase in enhancing lesions, which subsequently increased the contrast and contrast-to noise ratios. In the qualitative analysis, both readers found all tumors clearly delineated on HIRE imaging. Compared to T2-weighted FSE the tumor delineation with HIRE was better in nine patients, equal in four patients and less in one patient. Compared to the FLAIR images HIRE was rated superior in three patients, equal in nine patients and inferior in another three patients. Delineation of the enhancing tumor parts was possible with HIRE in all patients. HIRE images present significant less image artifacts than FLAIR images due to reduced inflow effects. CONCLUSIONS: The presented T2 based HIRE sequence is an alternative to the T1 based FLAIR sequence with the advantage of a better gray to white matter contrast and shorter measurement time. Due to the subtraction technique signal intensities from tissues with T2 relaxation times in the range between white matter and CSF are also partially affected depending on their T2 values. With respect to this undesired effect, an improvement in HIRE imaging will be expected by a self weighted subtraction algorithm. PMID- 11197936 TI - [Peri-interventional drug therapy in PTA of supra-aortic blood vessels]. AB - Percutaneous transluminal angioplasty in conjunction with stent implantation (PTAS) is the treatment of choice in several indications. Despite its frequent use in supraaortic arterial disease and the scientific effort to establish PTAS of the internal carotid artery there is relatively little data in the literature to provide an evidence-based ground for periinterventional medical therapy. This article reviews the current periprocedural protocols and gives an overview of the hemodynamic management as necessary in carotid PTAS. Furthermore, problems of antithrombotic therapy with heparin and platelet inhibitors are discussed and a short introduction into medical cerebroprotection and thrombolytic therapy in ischemic cerebrovascular events is given. PMID- 11197937 TI - [Chronic pain in the mid-foot area. Osteoarticular tuberculosis of the tarsal bones]. PMID- 11197938 TI - [Nobel Prize for Medicine 2000. Communicating nerve cells]. PMID- 11197939 TI - [Basic principles and general practice of digital photo- and video-documentation. 1]. PMID- 11197940 TI - C.T. Scanner dies. PMID- 11197941 TI - New approaches to cystic fibrosis. PMID- 11197943 TI - Dementia: causes, evaluation, and management. PMID- 11197942 TI - Hypertension in patients with type 2 diabetes. PMID- 11197944 TI - Issues of academic integrity in U.S. dental schools. AB - Evidence of violations of academic integrity can be identified at all levels of education. A survey on academic integrity was mailed in 1998 to the academic deans of all fifty-five U.S. dental schools, with a response rate of 84 percent. This survey showed that reported incidents of academic dishonesty occur in most dental schools, with the average school dealing with one or two cases a year. The most common incidents of dishonest behavior involved copying or aiding another student during a written examinations; the second most common involved writing an untrue patient record entry or signing a faculty member's name in a patient chart. Respondents indicated the major reason for failure to report academic dishonesty was fear of involvement because of time and procedural hassles and fear of repercussions from students and peers. PMID- 11197945 TI - Pilot study of dental hygienists' comfort and confidence levels and care planning for patients with disabilities. AB - A questionnaire assessing comfort levels and behaviors of dental hygienists concerning treatment of patients with special needs or disabilities was mailed to a random sample of 175 practicing dental hygienists in Idaho. All respondents had seen patients with disabilities, although 53 percent had never completed a formal course or received training directed specifically toward this population. Survey respondents were moderately to always comfortable treating special needs and disabled patients. Use of a wheelchair was the only disability in which clinicians were significantly more comfortable with treatment following completion of a course or receipt of training. Severity of a patient's disability and limited time were considered moderate to very high barriers to the provision of dental hygiene care. Recommended treatment planning techniques are being used to a limited extent, and respondents were slightly to moderately confident using alternative communication and treatment techniques. The findings suggest that although education or training was not strongly associated with comfort and confidence levels of these dental hygienists, they were interested in opportunities for further training in caring for patients with special needs. PMID- 11197946 TI - An initial evaluation of the Iowa Dental Surgical Simulator. AB - The University of Iowa colleges of dentistry and engineering are collaborating to build an effective but low-cost surgical simulator that uses force feedback to teach and assess the tactile skills of dentistry. A prototype simulator was built, and a formative evaluation examined the realism of the haptics and identified directions for future work. Using a cross-over design, twelve experienced practitioners probed two virtual teeth using two instruments attached to the force feedback device. The session was videotaped, the forces recorded, and a standardized questionnaire completed. Two analyses were conducted: an ANOVA examined practitioners' questionnaire responses, and a t-test analyzed the probing forces. Significant tooth order by instrument order interaction and instrument effects were found. Practitioners were generally satisfied. They preferred a standard joystick to an explorer, felt that two-dimensional graphics were sufficient, and emphasized that the existing vibration be eliminated. Random placement of caries should help teach generalized skills. PMID- 11197947 TI - Information for patients on dental school websites. PMID- 11197948 TI - Rethinking knowledge and pedagogy in dental education. AB - Dentistry as a profession has often been considered both art and science. Traditional dental education has attempted to address both; however, in many places only the science of dentistry is emphasized. The move toward competency based curricula in dental education requires an expansion of what constitutes meaningful knowledge in the curriculum and what pedagogies best support that curriculum. The scientific and technical knowledge considered foundational to clinical practice is not sufficient to teach competencies associated with the art of dentistry. Habermas, a social scientist, offers a way of looking beyond technical knowledge to consider two other forms of knowledge: practical and emancipatory. Pedagogy that supports development of practical and emancipatory knowledge includes problem-based learning and case methods, heuristics, reflective practica, journals, storytelling, and performance-based assessment methods. These important teaching strategies are being integrated into various dental curricula including a new competency-based dental curriculum at Marquette University's School of Dentistry. It will be critical for dental educators to continue developing these methods to provide efficient and effective education for future practitioners in both the art and science of dentistry. PMID- 11197949 TI - U.S. dental school applicants and enrollees: a ten year perspective. AB - Applications to dental schools increased throughout the 1990s until 1997. In 1998 this pattern reversed, and the number of dental school applicants has dropped each year since that time and continues to decline through the application cycle for the 2001-2002 first-year class. Possible reasons for the decline in applications include an abundance of financially rewarding career opportunities fueled by the robust U.S. economy, a reluctance by college students to assume more educational debt, an unfavorable view of healthcare careers in the light of managed care and declining federal reimbursement, and assumptions about the difficulty of gaining admittance to dental school given the high academic achievement of those who have been admitted in recent years. A national decline in the applicant pool does not necessarily translate into a decline for any given dental school. The quality of applicants, judged by grade point averages and Dental Admissions Test scores, is high. Nevertheless, the recent drop in dental school applicants is a cause for concern. Because recruitment must be approached as a process that takes years to yield results, stakeholders in dental education need to sustain vigorous recruiting efforts even in the best of times. PMID- 11197950 TI - The Oklahoma repair technique: a biomechanical study of a new suture repair technique. AB - We designed and evaluated the biomechanical advantages of a new (Oklahoma) suture technique for repairing flexor tendons in fresh, frozen cadaver specimens. Forty flexor digitorum profundi tendons from the middle three fingers were sharply cut and repaired with a number 3-0 braided polyester using the new technique and the Modified Kessler technique with and without an epitenon repair. The repaired tendons were then stressed to failure. The Modified Kessler with epitendon repair initiated gap formation on an average of 15.3 +/- 2.7 newtons and failed at 40.9 +/- 4.3 newtons. The Oklahoma suture technique with a running epitenon repair initiated gap formation on average of 48.6 (SD +/- 4.0) newtons and required an average load of 57.9 (SD +/- 3.0) newtons to fail. Thus, it was significantly stronger than the modified Kessler technique with epitendon repair (P < 0.01). The tendons repaired with the Oklahoma and epitenon repair suture technique did not form a 2 mm gap prior to failure. The epitendon repair increased the resistance to gap formation by 80% to 100% and the repair failure by 17.5% to 25% for both types of repairs. We concluded that the addition of the epitendon repair increases the tensile strength of the repair regardless of the core suture technique, and it should be used. In comparison with the Modified Kessler repair technique, the Oklahoma repair technique has superior tolerance to gap initiation, 2 mm gap formation, and physical failure of the repaired tendon. PMID- 11197951 TI - Improving the health of Oklahomans through clinical prevention, Part III: Immunizations and chemoprophylaxis. AB - Vaccines are one of the greatest achievements of biomedical science and public health and are clearly one of the most effective tools of clinical prevention. Diseases that once caused significant morbidity and mortality in Americans- particularly children--have been virtually eliminated from the population through effective immunization programs. But until these diseases have been eradicated globally we must continue to maintain high immunization levels to prevent their return; a 90% coverage rate has been set as the national goal for recommended vaccines in preschool age children. In Oklahoma we have only achieved that goal for two vaccines (measles and polio) and for the last several years we have ranked near the bottom in vaccine coverage rates compared to other states. Although achieving high vaccination rates in children involves numerous partners, private physicians must play a major role in that effort since they are the primary vaccine providers in the state. Physicians should also be alert to the vaccine needs of their adolescent and adult patients, particularly for pneumococcal disease, influenza, hepatitis A and B, and tetanus. This article describes current vaccination levels in Oklahoma children and adults for several routine and newly recommended vaccines and discusses the role of private physicians in maintaining and improving immunization coverage. PMID- 11197952 TI - Vaccine-preventable diseases. PMID- 11197953 TI - Leaders in medicine. Floyd Miller, MD. PMID- 11197954 TI - Monkey business. A tiny primate with a gene from a jellyfish raises scientists' hopes--and some serious ethical questions. PMID- 11197955 TI - Executive physical. There's a whole battery of new high-tech scans for those who can afford them. Are they worth it? PMID- 11197956 TI - Bearing no ill will. Employers are finding ways to support and retain the growing number of chronically ailing employees in America's work force. PMID- 11197957 TI - Reporter genes and imagene. PMID- 11197958 TI - Portal-Systemic shunts reduce asialoglycoprotein receptor density in rats. AB - The clinical usefulness of quantitative functional imaging techniques that use asialoglycoprotein receptor (ASGP-R) binding is based on the correlation between ASGP-R density and hepatic functional reserve. Portal-systemic shunting (PSS) is common in patients with cirrhosis and portal hypertension-the same group that is most frequently considered for such imaging. PSS occurs spontaneously through collateral vessels and from the creation of surgical shunts or placement of transjugular intrahepatic portal-systemic shunts (TIPS). Understanding the physiologic relationship between PSS and ASGP-R activity may aid in the interpretation of quantitative clinical imaging. This study was conducted to determine the relationship between PSS and ASGP-R density in the absence of parenchymal disease. METHODS: Sprague-Dawley rats with end-to-side portal systemic shunts and sham-operated control rats were imaged with 99mTC diethylenetriaminepentaacetic acid galactosyl-neoglycoalbumin. Pharmacokinetic modeling of the liver and heart time-activity data was used to measure ASGP-R concentration, as well as hepatic plasma volume and flow. RESULTS: The mean ASGP R density (nmol/g of liver) was significantly decreased in the shunted rats. Blood ammonia was significantly elevated, whereas hepatic plasma flow, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase levels were unaltered. Liver histology was normal in both groups. CONCLUSION: A significant change in the ASGP-R density occurs with PSS in the absence of parenchymal disease. PSS appears to be an independent variable affecting ASGP-R activity. This could prove clinically important during interpretation of quantitative imaging from patients with varying degrees of PSS based on underlying disease or the presence of a surgical shunt or TIPS device. PMID- 11197959 TI - Specific and rapid scintigraphic detection of infection with 99mTc-labeled interleukin-8. AB - Interleukin-8 (IL-8) is a chemotactic cytokine involved in activation and recruitment of neutrophils to areas of infection. In our previous studies in rabbits we tested 123I-labeled IL-8 for its potential to image infections and showed that IL-8 rapidly and efficiently accumulated in infectious foci. However, labeling of IL-8 with 123I is costly and laborious and the specific activity of the preparation was low. In this study IL-8 was labeled with 99mTc through the hydrazinonicotinamide (HYNIC) chelator. METHODS: The leukocyte receptor-binding capacity of the preparation was determined in vitro. Rabbits with Escherichia coli abscesses were injected intravenously with 7 MBq 99mTc-HYNIC-IL-8. Biodistribution of the radiolabel was determined by gamma camera imaging and tissue counting at 8 h after injection. 99mTc-HYNIC-lysozyme was used as a size matched control. RESULTS: The leukocyte receptor-binding capacity of the 99mTc HYNIC-IL-8 preparation was preserved as determined in vitro, but labeling efficiency was modest with a specific activity of 3 MBq/microg. 99mTc-HYNIC-IL-8 accumulated rapidly in the abscess up to 0.33 +/- 0.06 percentage injected dose per gram (%ID/g) at 8 h after injection (vs. 0.025 +/- 0.003 %lD/g for 99mTc HYNIC-lysozyme). Total uptake in the abscess was 4.9 +/- 0.7 %ID (vs. 0.44 +/- 0.05 %ID for 99mTc-HYNIC-lysozyme). Abscess-to-contralateral muscle ratios increased up to 127 +/- 23 (compared with 6.7 +/- 1.1 for 99mTc-HYNIC-lysozyme) and abscess-to-blood ratios increased to 11.9 +/- 2.2 (0.24 +/- 0.03 for 99mTc HYNIC-lysozyme). The radiolabel was excreted renally, with a retention in the kidneys of 28 %ID. Gamma camera imaging rapidly visualized the abscess from 1 h after injection onward, with abscess-to-background ratios improving with time up to 22 at 8 h after injection (vs. 2.7 for 99mTc-HYNIC-lysozyme), as determined by quantitative analysis of the images. Most important, only a transient (30 min) moderate drop of leukocyte counts and no leukocytosis were observed after injection of an imaging dose of 99mTc-HYNIC-IL-8. CONCLUSION: IL-8 can be labeled with 99mTc using HYNIC as a chelator. By this method the leukocyte receptor binding capacity is preserved. The preparation allows rapid visualization of infection in a rabbit model with high target-to-background ratios. The mild transient drop of leukocyte counts and the absence of leukocytosis suggest that 99mTc-HYNIC-IL-8 may be used as an imaging agent with only mild and transient side effects. PMID- 11197960 TI - Myocardial lipid metabolism in compensated and advanced stages of heart failure: evaluation by canine pacing model with BMIPP. AB - The normal myocardium uses primarily fatty acid as its energy source, but, as heart failure develops, the myocardial fatty acid metabolism is limited. In this study, impairment of the lipid metabolism in heart failure was serially evaluated with 123I-(rho-iodophenyl)3-(R,S)-methylpentadecanoic acid (BMIPP), a radioiodinated fatty acid analog. METHODS: Rapid ventricular pacing was introduced in 10 beagle dogs. Dogs were subjected to hemodynamic assessment and measurement of catecholamine before and after pacing. After 1 wk (group A; n = 4) and 4 wk (group B; n = 6) of pacing, BMIPP was injected directly into the left anterior descending artery; its extraction, retention, and washout rate in the early phase were calculated, and the metabolites in the myocardium were evaluated using high-performance liquid chromatography. These factors were compared with those of healthy control animals (group C; n = 6). RESULTS: The left ventricular ejection fraction and cardiac output decreased significantly in groups A and B after pacing. The pulmonary capillary wedge pressure did not change in group A but increased significantly in group B. Plasma norepinephrine increased progressively as heart failure developed but did not reach statistical significance. The washout rate in the early phase increased, significantly in groups A and B compared with that of group C. Extraction and retention of BMIPP did not change in group A. In group B, extraction tended to decrease and retention decreased significantly compared with that of group C. The levels of full metabolite formed by complete oxidation of BMIPP decreased, and backdiffusion of BMIPP increased significantly in groups A and B compared with that of group C. Myocardial blood flow did not change among the three groups. CONCLUSION: Our study indicates that myocardial fatty acid oxidation begins to be inhibited and that washout of BMIPP increases in the compensated stage of left ventricular dysfunction but that myocardial extraction and retention of fatty acid are definitely impaired in the advanced stage of heart failure. Therefore, as assessed by BMIPP, the myocardial lipid metabolism is related to the pathophysiology of the development and worsening of heart failure. PMID- 11197961 TI - Challenges in development and use of radiopharmaceuticals. PMID- 11197962 TI - Immunoscintigraphy of aortic dissection with 99mTc-labeled murine anti-smooth muscle myosin monoclonal antibody in rats. AB - Aortic dissection is among the most common of fatal conditions of the aorta. Prompt and accurate diagnosis of the site and extent of the lesion is necessary for adequate therapy. However, this catastrophic disease, characterized by extensive damage to smooth muscle cells, lacks specific signs and symptoms. As a result, the diagnosis is still frequently missed today and a new diagnostic method to specifically identify aortic dissection would be attractive. The purpose of this study was to examine the feasibility of radioimmunoscintigraphy using 99mTc-anti-smooth muscle myosin monoclonal antibody (SM-MAb) for the noninvasive diagnosis of aortic dissection in the rat experimental model. METHODS: The accumulation of 99mTc-anti-SM-MAb was studied, and scintigraphic imaging with 99mTc-anti-SMMAb was performed in rats immediately after experimental aortic dissection and 1 and 2 wk later. RESULTS: The radioactivity of 99mTc-anti-SM-MAb in the dissected aorta showed a significant increase compared both with the normal portion of the aorta and with blood 6 h after injection of the radiotracer; the ratio of the percentage injected dose per gram (%lD/g) in the lesion to that retained in the normal portion was 4.17 +/- 1.47. Scintigraphic imaging with 99mTc-anti-SM-MAb allowed distinct visualization of the dissected aorta with specific accumulation of antibody 6 h after tracer injection. Selective accumulation of the tracer in the dissected portion of the aorta persisted even 1 wk after aortic injury, allowing clear visualization of the dissected lesion by scintigraphy. CONCLUSION: Radioimmunoscintigraphy using anti-SM-MAb is a potentially useful noninvasive diagnostic method for imaging aortic dissection. PMID- 11197963 TI - In vivo detection of deposition of radiolabeled lupus antikidney antibody and its inhibition by soluble antigen. AB - This investigation in an animal model was designed to test the feasibility of using radiolabeled lupus antikidney antibody to show renal deposition in vivo and the ability to block this deposition with a binding peptide. METHODS: BALB/c mice received injections of radiolabeled murine anti-DNA antibody, antibody with no DNA binding capability, and DNA antibody simultaneously with blocking peptide. RESULTS: Significantly higher renal deposition of anti-DNA antibody than of antibody without DNA binding capability occurred in the animals at 48 h after injection (5.21% of the injected dose per gram of tissue versus 2.5%, P < 0.0004) and at 7-8 d after injection (1.44% versus 0.20%, P < 0.00004). The simultaneous injection of blocking peptide with anti-DNA binding antibody significantly reduced the renal deposition of the anti-DNA antibody at 48 h (1.53%, P < 0.00001) and at 7-8 d (0.64%, P < 0.0017). CONCLUSION: This study showed the feasibility of using a radiolabeled antibody to evaluate deposition of anti-DNA antibody in the kidney and the successful use of a peptide to block antibody deposition-a strategy that may be useful for renal preservation in lupus. These data support the possibility of using antikidney-labeled antibodies to evaluate immunologic renal disease in vivo in humans. PMID- 11197964 TI - Joint scintigraphy in rabbits with 99mtc-N-[3-(triethylammonio)propyl]-15ane-N5, a new radiodiagnostic agent for articular cartilage imaging. AB - The aim of this study was to investigate joint scintigraphy in rabbits with 99mTc N-[3-(triethylammonio)propyl]-15ane-N5 (NTP 15-5), a new radiopharmaceutical that specifically localizes in cartilaginous tissues. METHODS: Scans obtained after intravenous injection of the 99mTc-labeled compound in normal and arthropathy induced rabbits were compared with those of the bone-imaging agent 99mTc methylene diphosphonate (99mTc-MDP). RESULTS: The radioactive uptake of 99mTc-NTP 15-5 was detected in cartilaginous tissues 5 min after injection and was stable for 2 h. The uptake intensity was related to age and joint disease severity, and cartilage alterations not revealed by radiography induced a significant decrease of radiotracer uptake. On the other hand, imaging performed with 99mTc-MDP did not reveal the early changes in arthrosis but was more specific for bone remodeling in advanced stages of diseases or in inflammatory processes. CONCLUSION: Our results indicate that 99mTc-NTP 15-5 could be a good tracer for human arthrosic and arthritic cartilage detection, especially for the early diagnosis of joint diseases. PMID- 11197965 TI - Two-step targeting of xenografted colon carcinoma using a bispecific antibody and 188Re-labeled bivalent hapten: biodistribution and dosimetry studies. AB - Radioimmunotherapy (RIT) is currently being considered for the treatment of solid tumors. Although results have been encouraging for pretargeted 131I RIT with the affinity enhancement system (AES), the radionuclide used is not optimal because of its long half-life, strong gamma emission, poor specific activity, and low beta particle energy. 188Re, though unsuitable for direct antibody labeling, could be used with the AES two-step targeting technique. The purpose of this study was to compare the distribution and dosimetry of a bivalent hapten labeled with 188Re or 125I. For dosimetry calculations and biodistribution data, 125I was substituted for 131I. METHODS: After preliminary injection of a bispecific anticarcinoembryonic antigen (CEA) or antihapten antibody (Bs-mAb F6-679), AG 8.1 or AG 8.0 hapten radiolabeled with 188Re or 125I was injected into a nude mouse model grafted subcutaneously with a human colon carcinoma cell line (LS-174-T) expressing CEA. A dosimetry study was performed for each animal from the concentration of radioactivity in tumor and different tissues. RESULTS: Radiolabeling of AG 8.1 with 125I afforded a 40% yield with a specific activity of 11.1 MBq/nmol after purification. Radiolabeling of AG 8.0 with 188Re afforded a 72% yield with a specific activity of 31.82 MBq/nmol. In all experiments, the percentage of tumor uptake of 125I-AG 8.1 was always significantly greater than that of 188Re-AG 8.0. The corresponding tumor-to-tissue ratios reflected uptake values. The least favorable tumor-to-normal tissue ratios in the dosimetry study were 8.1 and 8.5 for 131I (tumor-to-blood ratio and tumor-to-kidney ratio, respectively) and 2.3 for 188Re (tumor-to-intestine ratio). CONCLUSION: This study indicates that 188Re can be used for radiolabeling of hapten in two-step radioimmunotherapy protocols with the AES technique. 188Re has a greater range than 131I, which should allow the treatment of solid tumors around 1 cm in diameter. Although the method used for hapten radiolabeling did not provide optimal tumor uptake, the use of a bifunctional chelating agent associated with AG 8.1 should solve this problem. PMID- 11197966 TI - Nuclear medicine chemistry. PMID- 11197967 TI - Evaluation of 99mTc-RP128 as a potential inflammation imaging agent: human dosimetry and first clinical results. AB - 99mTc-RP128 is a bifunctional peptide chelate designed to target the tuftsin receptor, expressed by neutrophils, monocytes, and macrophages. Studies in animal models of both infectious and noninfectious inflammation have shown a positive correlation between accumulation of 99mTc-RP128 and quantitative measures of inflammation. A phase 1 trial was conducted with the objective of determining the safety, biodistribution, and human dosimetry of 99mTc-RP128 in eight healthy volunteers. For evaluation of the potential of 99mTc-RP128 for imaging sites of inflammation, 10 patients with active rheumatoid arthritis were studied. METHODS: Normal biodistribution was determined using the conjugate view method up to 24 h after intravenous injection of 280 MBq 99mTc-RP128. Dosimetry calculations were based on standard MIRD methodology, using the International Commission on Radiological Protection model 30 of the gastrointestinal tract and a voiding bladder model with an interval of 4.8 h. For rheumatoid arthritis patients, whole body scans and spot views of the hands, knees, and feet were obtained at 1 and 3 h after injection of 475 MBq 99mTc-RP128. RESULTS: 99mTc-RP128 was cleared rapidly from the blood by renal excretion, and no major organs showed significant accumulation. The synovia of the major joints were visualized for all subjects. The effective dose equivalent and the effective dose were calculated to be 0.011 and 0.0094 mSv/MBq, respectively. The highest dose was to the bladder wall, which received 0.076 mGy/MBq. In all rheumatoid arthritis patients, we observed a markedly increased uptake in several affected joints. Painful and swollen joints were detected with a sensitivity of 76% and 69%, respectively. Seventy-three percent of the joints with radiographic signs of erosion were scintigraphically positive. In some patients, lines of increased activity were observed and were considered to correspond to uptake in the synovium lining tendon sheaths in the wrists and hands. CONCLUSION: This study shows that 99mTc-RP128 is safe and can successfully be used to visualize clinically affected joints in patients with long-standing rheumatoid arthritis. A proposed radioactive dose of 450-500 MBq will produce an effective dose well within the range of effective doses for commonly used radiopharmaceuticals. PMID- 11197969 TI - Nuclear medicine in the military. PMID- 11197968 TI - Biologic dosimetry of bone marrow: induction of micronuclei in reticulocytes after exposure to 32P and 90Y. AB - Bone marrow is the dose-limiting organ in targeted radionuclide therapy. Hence, determination of the absorbed dose to bone marrow from incorporated radionuclides is a critical element in treatment planning. This study investigated the potential of the micronucleus assay in peripheral blood reticulocytes (MnRETs) as an in vivo biologic dosimeter for bone marrow. METHODS: After intravenous administration of 32P-orthophosphate or 90Y-citrate in Swiss Webster mice, DNA damage induced in bone marrow erythroblastoid cells was measured by subsequent scoring of MnRETs in peripheral blood. The response to exponentially decreasing dose rates was calibrated by irradiating animals with external 137Cs-gamma-rays. The gamma-ray dose rate was decreased exponentially, with the dose-rate decrease half-time corresponding to the effective clearance half-time (Te) of the radioactivity from the femoral bone (Te = 64 h for 90Y-citrate and Te = 255 h for 32P-orthophosphate). RESULTS: The maximum MnRETs frequency occurred on the second and third day after injection of 90Y-citrate and 32P-orthophosphate, respectively. The same pattern was observed for exponentially decreasing dose rates of 137Cs-gamma-rays. For each type of exposure, the maximum MnRETs frequency increased in a dose-dependent manner. Using the calibrated dosimeter, the initial dose rates to the marrow per unit of injected activity were 0.0020 cGy/h/kBq and 0.0026 cGy/h/kBq for 32P-orthophosphate and 90Y-citrate, respectively. CONCLUSION: Micronuclei in peripheral blood reticulocytes can be used as a noninvasive biologic dosimeter for measuring absorbed dose rate and absorbed dose to bone marrow from incorporated radionuclides. PMID- 11197970 TI - Paclitaxel-Based chemotherapy for non-small cell lung cancer: predicting the response with 99mTc-tetrofosmin chest imaging. AB - The purpose of this study was to retrospectively predict the chemotherapeutic response to paclitaxel for non-small cell lung cancer (NSCLC) using 99mTc tetrofosmin (TF) uptake and to detect the expression of 170-kDa multidrug resistance-mediated P-glycoprotein (MDR-Pgp). METHODS: Before chemotherapy with paclitaxel, 20 patients with stage IIIb or IV NSCLC were enrolled in this study to undergo early and delayed 99mTc-TF chest imaging for calculating tumor-to normal lung ratios (T/NL) and retention indices (RI) for assessment of the MDR Pgp in NSCLC. RESULTS: The early and delayed mean T/NLs were 1.59 +/- 0.25 and 1.50 +/- 0.25, respectively, for 10 patients with a good response and 1.09 +/- 0.09 and 1.03 +/- 0.05, respectively, for 10 patients with a poor response. The differences were shown to be significant (P < 0.001) by independent Student t tests. However, no significant differences (P = 0.801) between good-response patients (-5.70% +/- 3.67%) and poor-response patients (-5.23% +/- 4.51%) were found in RI. In addition, other prognostic factors (age, sex, tumor size, stage, and cell type) were not significantly different between good-response patients and poor-response patients. CONCLUSION: 99mTc-TF chest images are potential tools for understanding MDR-Pgp expression in NSCLC and for predicting the chemotherapeutic response to paclitaxel. PMID- 11197971 TI - Hypoxia-Induced increase in FDG uptake in MCF7 cells. AB - Recent clinical data indicate that tumor hypoxia negatively affects the treatment outcome of both radiotherapy and surgery in various cancers, emphasizing the need for noninvasive detection of tumor hypoxia. Several studies have shown an increased uptake of FDG in hypoxic regions of xenografts, suggesting the use of PET with FDG as a potential technique. In this study, we examine the mechanism underlying the hypoxia-induced increase of FDG uptake in the human breast carcinoma cell line MCF7. METHODS: The uptake of 3H-FDG into MCF7 cells was determined after incubation under hypoxic (0% oxygen) or normoxic conditions, with or without redox agents, for varying time periods. In addition, the effects of the redox agents on the glucose transporter activity and the hexokinase activity were determined independently, and the effects of hypoxia on glucose transporter protein and hexokinase levels were assessed. RESULTS: A more than twofold increase (2.53 +/- 0.79; P < 0.005) in 3H-FDG uptake was observed under hypoxic conditions, but no changes in the cellular levels of glucose transporter proteins or hexokinase were observed. A reducing agent, dithiothreitol (DTT), also caused an increase in 3H-FDG uptake but failed to affect uptake under hypoxic conditions. This indicates that the mechanisms by which hypoxia and DTT affect 3H-FDG uptake might be the same. The oxidizing agent p chloromercuribenzenesulfonic acid (pCMBS) had no effect on 3H-FDG uptake under normoxic conditions but counteracted the effect of hypoxia. DTT caused an increase in glucose transporter activity, whereas it had no effect on hexokinase activity. pCMBS had no effect on either glucose transporter activity or hexokinase activity. CONCLUSION: The hypoxia-induced increase in 3H-FDG uptake in MCF7 cells is the result, in part, of an increase in glucose transporter activity resulting from the modification (reduction) of thiol group(s) in the glucose transport protein(s). Modulation of hexokinase activity is probably not involved in the hypoxia-induced increase in 3H-FDG uptake in these cells. PMID- 11197972 TI - The severity of pulmonary emphysema investigated with fractal analysis: regional dependence. PMID- 11197973 TI - Somatostatin receptor scintigraphy and gallium scintigraphy in patients with sarcoidosis. AB - Somatostatin receptor scintigraphy (SRS) has been shown to reveal sarcoidosis sites. The aim of this study was to prospectively compare SRS and gallium scintigraphy in the evaluation of pulmonary and extrapulmonary involvement in patients with proven sarcoidosis. METHODS: Eighteen patients with biopsy-proven sarcoidosis were included. Nine were or recently had been receiving steroid therapy at the time of the examination. Planar gallium scintigraphy (head, chest, abdomen, and pelvis) and thoracic SPECT were performed at 48-72 h after injection of a mean dose of 138 +/- 21 MBq 67Ga. Planar SRS and thoracic SPECT were performed at 4 and 24 h after injection of a mean dose of 148 +/- 17 MBq 111n pentetreotide. RESULTS: Gallium scintigraphy found abnormalities in 16 of 18 patients (89%) and detected 64 of 99 clinically involved sites (65%). SRS found abnormalities in 18 of 18 patients and detected 82 of 99 clinically involved sites (83%). Of the 9 treated patients, gallium scintigraphy found abnormalities in 7 (78%), detecting 23 of 39 clinically involved sites (59%), whereas SRS found abnormalities in 9, detecting 32 of 39 clinically involved sites (82%). CONCLUSION: This study suggests that, compared with gallium scintigraphy, SRS appears to be accurate and contributes to a better evaluation of organ involvement in sarcoidosis patients, especially those treated with corticosteroids. PMID- 11197974 TI - Looking ahead to government regulation and response in nuclear medicine. PMID- 11197975 TI - Parametric images of antibody pharmacokinetics in Bi213-HuM195 therapy of leukemia. AB - Kinetic analysis of gamma camera patient images can provide time-dependent information about antibody behavior. Current region-of-interest-based techniques for the kinetic analysis of these images rely on user selection and drawing of regions to be analyzed. Such analyses do not reveal unexpected kinetic activity outside of the selected regions of interest and do not provide a whole-image assessment regarding the pharmacokinetics of an agent. At Memorial Sloan Kettering Cancer Center, a method for generating images in which the pixel value represents a kinetic parameter has been developed. This work extends the method into a new application in which whole-body parametric images are used to examine the kinetics of Bi213-HuM195 in patients with leukemia. METHODS: Bi213-HuM195 is typically administered in multiple injections over 2-4 d, yielding a progressive increase in the amount of antibody administered. Patients are injected with individual doses while positioned in a gamma camera, and imaging is initiated at the start of the injection. The acquisition is performed in dynamic mode with images collected at several time intervals over 1 h. Using software developed in house, images are corrected for patient movement through iterative alignments, decay corrected, and summed to yield a series of images over regular time intervals. Parametric rate images are obtained by fitting a linear expression to the counts in each pixel. In this study, rate images from a patient's first injection were compared with rate images from the last injection. RESULTS: The conventional planar images of antibody distribution showed significant uptake in liver, spleen, and marrow, whereas the generated rate images displayed different patterns, sometimes with negative values in liver and spleen and positive values in marrow, reflecting clearance and uptake rates rather than total accumulation. The impact of the progressive increase in antibody administration was observed by comparing the first with the last rate images. Interpatient comparisons were also made and showed that rate image patterns varied depending on patient-specific conditions such as the amount of disease and previous therapies undergone by the patient. CONCLUSION: Rate images make it possible to succinctly display kinetic information about an agent's behavior over the entire acquired image. PMID- 11197976 TI - Prediction of the usefulness of combined mammography and scintimammography in suspected primary breast cancer using ROC curves. AB - The aim of this study was to compare the accuracy of 99mTc methoxyisobutylisonitrile scintimammography (SMM) and conventional mammography in patients presenting with suspected primary breast cancer. Receiver-operating characteristic (ROC) curve analysis was applied to determine if a combination of x-ray mammography (XMM) and SMM was more accurate than a single test alone. METHODS: The results of SMM, XMM, and a combination of both studies performed over a 3-y period on 374 suspicious lesions in 353 patients with no previous history of breast cancer were reviewed. Each scan report was reviewed and graded as follows: grade 1, definitely normal or benign; grade 2, probably normal or benign; grade 3, equivocal; grade 4, probably cancer; and grade 5, definitely cancer. The results were verified by pathologic examination of biopsy material obtained from each suspicious mass. ROC curves were generated from these results. RESULTS: There were 204 malignant breast tumors and 170 nonmalignant breast lesions. SMM diagnosed correctly 181 breast cancers and was true-negative in 122 benign breast lesions: sensitivity, 89%; specificity, 71%; positive predictive value (PPV), 79%; and negative predictive value (NPV), 84%. XMM diagnosed correctly 143 malignant tumors and was true-negative in 117 nonmalignant lesions. The sensitivity, specificity, PPV, and NPV for XMM were 70%, 69%, 73%, and 66%, respectively. Using a combination of the two tests, the combined sensitivity was 93%, specificity was 72%, PPV was 80%, and NPV was 90%. Using the index of the area under the ROC curve obtained by the rating method showed that the combination of XMM and SMM was significantly more accurate than either of the individual tests if performed alone (P < 0.05). CONCLUSION: This study shows that the combination of XMM and SMM produces more accurate results than either modality alone. Therefore, if there is doubt about the accuracy of XMM, SMM should be used as the second-line test in breast imaging. PMID- 11197977 TI - 99mTc-MIBI scintigraphy in musculoskeletal tumors. AB - The aim of this study was to assess the value of 99mTc-hexakis2 methoxyisobutylisonitrile (MIBI) scintigraphy in patients with clinical and radiologic features of primary or metastatic musculoskeletal tumors. METHODS: The scintigraphic findings for 84 patients were compared with the surgical and histologic findings. Each patient underwent three-phase bone scanning with 99mTc methylene diphosphonate (MDP) and dynamic and static MIBI scintigraphy. The MIBI scans were evaluated by visual and quantitative analysis. The count ratio of the lesion to the adjacent or contralateral normal area (L/N) was calculated from the region of interest drawn on the MIBI scan. The Mann-Whitney test was used to determine the differences between the uptake ratios of malignant and benign lesions. RESULTS: Although increased MDP uptake was not specific for bone malignancy, a significant difference was found between benign tumors (L/N = 1.22 +/- 0.43) and malignant tumors (L/N = 2.25 +/- 1.03) on MIBI scans. Sensitivity and specificity were 81% and 87%, respectively. Forty-six of 53 proven benign lesions did not show significant MIBI uptake. The negative predictive value was 88%. In all seven sites of pathologic fracture, significant uptake was seen. However, three malignant lesions were not detected by MIBI scintigraphy, whereas seven benign lesions showed false-positive results. CONCLUSION: The major diagnostic worth of MIBI scintigraphy is its high negative predictive value. Although not capable of replacing tissue biopsy as a definitive diagnostic modality for musculoskeletal neoplasms, MIBI scintigraphy does appear to have a role in better preoperative assessment and in distinguishing between pathologic and simple fractures. PMID- 11197978 TI - Study of quantitative oral radioactivity in salivary gland scintigraphy and determination of the clinical stage of Sjogren's syndrome. AB - In this study, the oral radioactivity seen in salivary gland scintigraphy, which was established entirely on the basis of radioactive saliva secreted by the parotid and submandibular glands, was evaluated quantitatively in healthy volunteers and in patients with Sjogren's syndrome. METHODS: Salivary gland scintigraphy and labial biopsy were performed on 70 patients with Sjogren's syndrome. After intravenous administration of 99mTc-sodium pertechnetate, dynamic scintigraphy was performed and time-activity curves for the oral cavity and four major salivary glands were generated. Lemon juice stimulation was delivered at 40 min. The prestimulatory oral activity index, poststimulatory oral activity index, and time interval between the vascular perfusion peak and the prestimulated maximum oral activity point were calculated to quantify the oral activity. Other glandular functional parameters-namely, maximum accumulation (MA), maximum secretion, secretion velocity, time at maximum count, time interval from stimulation to minimum count, and uptake ratio (UR) of the parotid and submandibular glands-were also calculated. Salivary gland scintigraphy was also performed on 21 healthy subjects with no evidence of salivary gland malfunction. RESULTS: Histopathologic grade 1 or 2 was found in 29 patients and grade 3 or 4 was found in 41 patients, and they were regarded as being in the early and advanced stages of Sjogren's syndrome, respectively. After overall analysis, all of the oral activity indices and the MA and UR of the submandibular gland clearly decreased as clinical severity progressed, and statistically significant differences were observed. CONCLUSION: New oral activity indices correlated with the stage of Sjogren's syndrome, and these quantitative oral indices together with certain glandular parameters (mainly MA and UR of the submandibular gland) were found to be sensitive enough to distinguish the disease severity of Sjogren's syndrome. PMID- 11197979 TI - The promising role of 18F-FDG PET in detecting infected lower limb prosthesis implants. AB - The purpose of this study was to evaluate the feasibility of using 18F-FDG and PET for the detection of infection associated with lower limb arthroplasty. METHODS: Seventy-four prostheses in 62 patients in whom infection was suspected after artificial hip or knee placement were studied with this technique. Images were obtained 60 min after an intravenous injection of FDG. The images were interpreted as positive for infection if tracer uptake was increased at the bone prosthesis interface. A final diagnosis was made by surgical exploration or clinical follow-up for 1 y. PET results were compared with the follow-up outcome in all patients. RESULTS: The sensitivity, specificity, and accuracy of PET for detecting infection associated with knee prostheses were 90.9%, 72.0%, and 77.8%, respectively. The sensitivity, specificity, and accuracy of PET for detecting infection associated with hip prostheses were 90%, 89.3%, and 89.5%, respectively. Overall, the sensitivity was 90.5% and the specificity was 81.1% for detection of lower limb infections. CONCLUSION: FDG PET is a useful imaging modality for detecting infections associated with lower limb arthroplasty and is more accurate for detecting infections associated with hip prostheses than for detecting infections associated with knee prostheses. PMID- 11197980 TI - Recovery of the cardiac adrenergic nervous system after long-term beta-blocker therapy in idiopathic dilated cardiomyopathy: assessment by increase in myocardial 123I-metaiodobenzylguanidine uptake. AB - In chronic heart failure, elevated plasma norepinephrine (NE) levels and a disparity between the neuronal release and the effective reuptake of NE lead to an increased concentration of NE in the presynaptic cleft, causing a downregulation of the myocardial beta-adrenoceptors. The clinical and prognostic effectiveness of beta-blocker therapy has been shown in patients with chronic heart failure in several large trials. The purpose of this study was to investigate the effect of long-term beta-blocker therapy on the cardiac adrenergic nervous system as assessed by the myocardial uptake of 123I metaiodobenzylguanidine (MIBG), an analog of NE, in idiopathic dilated cardiomyopathy (IDC). METHODS: In 10 patients with IDC and stable chronic heart failure the myocardial MIBG uptake was measured at baseline and at 1 y (median, 11.5 mo) after treatment with beta-blockers (metoprolol, n = 5; bisoprolol, n = 1; and carvedilol, n = 4) in addition to standard medication. In parallel with the changes in MIBG uptake, the New York Heart Association functional class, the left ventricular ejection fraction (LVEF), and the left ventricular end-diastolic diameter (LVEDD) were documented before and after 1 y of therapy with beta blockers. RESULTS: During the 1-y follow-up, a significant increase in myocardial 123I-MIBG uptake (P = 0.005) in parallel with an improved LVEF (P = 0.005) and a reduced LVEDD (P = 0.019) was found. A trend toward an improvement of the New York Heart Association functional class under the beta-blocker therapy (P = 0.139) was also found. CONCLUSION: Assessment of the myocardial 123I-MIBG uptake is a useful noninvasive tool for evaluating changes in cardiac sympathetic nerve activity under medical therapy. Long-term treatment with beta-blockers in IDC causes a recovery of the cardiac adrenergic nervous system concomitantly with a clinical and hemodynamic improvement. PMID- 11197981 TI - An evaluation of myocardial fatty acid and glucose uptake using PET with [18F]fluoro-6-thia-heptadecanoic acid and [18F]FDG in Patients with Congestive Heart Failure. AB - Understanding the metabolic consequences of heart failure is important in evaluating potential mechanisms for disease progression and assessing targets for therapies designed to improve myocardial metabolism in patients with heart failure. PET is uniquely suited to noninvasively evaluate myocardial metabolism. In this study, we investigated the kinetics of 14(R,S)-[18F]fluoro-6-thia heptadecanoic acid (FTHA) and [18F]FDG in patients with stable New York Heart Association functional class III congestive heart failure and a left ventricular ejection fraction of no more than 35%. METHODS: Twelve fasting patients underwent dynamic PET studies using [18F]FTHA and FDG. From the dynamic image data, the fractional uptake rates (Ki) were determined for [18F]FTHA and FDG. Subsequently, serum free fatty acid and glucose concentrations were used to calculate the myocardial free fatty acid and glucose uptake rates, respectively. Uptake rates were compared with reported values for [18F]FTHA and FDG in subjects with normal left ventricular function. RESULTS: The average Ki for [18F]FTHA was 19.7 +/- 9.3 mL/100 g/min (range, 7.2-36.0 ml/100 g/min). The average myocardial fatty acid use was 19.3 +/- 2.3 mmol/100 g/min. The average Ki for FDG was 1.5 +/- 0.37 mL/100 g/min (range, 0.1-3.3 mL/100 g/min), and the average myocardial glucose use was 12.3 +/- 2.3 mmol/100 g/min. CONCLUSION: Myocardial free fatty acid and glucose use in heart failure can be quantitatively assessed using PET with [18F]FTHA and FDG. Myocardial fatty acid uptake rates in heart failure are higher than expected for the normal heart, whereas myocardial glucose uptake rates are lower. This shift in myocardial substrate use may be an indication of impaired energy efficiency in the failing heart, providing a target for therapies directed at improving myocardial energy efficiency. PMID- 11197982 TI - Measurement of myocardial blood flow with PET using 1-11C-acetate. AB - 11C-acetate has been used extensively for the noninvasive assessment of myocardial oxygen consumption and viability with PET. The use of early uptake of acetate by the heart to measure myocardial perfusion has been proposed. This study evaluated the application of 11C-acetate for absolute measurement of myocardial blood flow using a simple compartmental model that does not require blood sampling. METHODS: Eight healthy volunteers and 13 subjects with concentric left ventricular hypertrophy were studied under resting conditions with both 11Cacetate and 15O-water. Myocardial blood flow with 11C-acetate was obtained by fitting the first 3 min of the blood and tissue tracer activity curves to a two compartment model. Flows obtained were compared with a validated approach using 15O-water. RESULTS: In healthy volunteers, regional myocardial perfusion at rest estimated with 11C-acetate was comparable with values obtained with 15O-water (1.06 +/- 0.25 and 0.96 +/- 0.12 mL/g/min, respectively). Perfusion in subjects with left ventricular hypertrophy was also comparable if the recovery coefficient (FMM) used was corrected for ventricular mass. If a fixed FMM was used, flow was greatly overestimated. FMM could be estimated from left ventricular mass (FMM = 0.46 + 0.002 x mass, r = 0.86, P < 0.0001). CONCLUSION: The results of this study suggest that 11C-acetate can be applied to quantitatively estimate myocardial perfusion under resting conditions using a two-compartment model without the need for blood sampling, provided that an appropriate FMM is chosen. This approach should increase the usefulness of this tracer and obviate administration of a separate tracer to independently measure perfusion. PMID- 11197983 TI - Impact of FDG PET on patients with differentiated thyroid cancer who present with elevated thyroglobulin and negative 131I scan. AB - FDG PET is increasingly performed in patients with differentiated thyroid cancer who present with elevated human thyroglobulin (hTG) levels and negative 131I scan. The aim of this study was to evaluate the impact of FDG PET on treatment in these patients. METHODS: A total of 118 FDG PET studies were performed on 64 patients, and follow-up data were available for all patients. Whole-body images were acquired 1 h after intravenous injection of 370 MBq (10 mCi) FDG using a PET scanner with an axial field of view of 16.2 cm. Tumor-suspicious FDG PET studies were evaluated by histology, cytology, 131I uptake, CT or MRI, and follow-up of hTg levels. The therapeutic consequence was noted for each patient. Moreover, results of FDG PET were correlated with hTg levels. RESULTS: Forty-four patients had positive scans, which were proven to be true-positive in 34 patients, whereas 7 patients had false-positive findings. Two patients exhibited a secondary malignancy. One patient did not fit in any category, having true-positive, false positive, and false-negative findings. On the other hand, 20 patients had negative scans. These were true-negative findings in 5 patients, whereas the remaining 15 patients had false-negative results. Accordingly, the positive predictive value of FDG PET was 83% (34/41), whereas the negative predictive value was 25% (5/20). Treatment was directly changed in 19 of 34 patients with true-positive PET studies: 18 patients had further surgery, and 4 patients were referred for external irradiation, 3 of them after incomplete removal of local recurrences. FDG PET showed widespread disease in 7 patients; thus, palliative treatment, rather than curative therapy, was initiated. True-positive FDG PET findings were correlated positively with increasing hTg levels (i.e., FDG PET was true-positive in 11%, 50%, and 93% of patients with hTg levels of <10, 10-20, and >100 microg/L, respectively). CONCLUSION: FDG PET is a valuable diagnostic tool in patients with differentiated thyroid cancer who present with increased hTg levels and negative 131I scans because it permits selection of patients for surgery, which may be curative. FDG PET is most promising at hTg levels of >10 microg/L. PMID- 11197984 TI - Clinical usefulness of FDG PET in differentiated thyroid cancer. PMID- 11197985 TI - Relationship between preoperative viability and postoperative improvement in LVEF and heart failure symptoms. AB - The presence of myocardial viability is predictive of improvement in regional left ventricular (LV) function after revascularization. Studies on predicting improvement in global LV function are scarce, and the amount of viable myocardium needed for improvement in LV ejection fraction (LVEF) after revascularization is unknown. Moreover, whether the presence of viability is associated with relief of heart failure symptoms after revascularization is uncertain. Hence, the aims were to define the extent of viable myocardium needed for improvement in LVEF and to determine whether preoperative viability testing can predict improvement in heart failure symptoms. METHODS: Patients (n = 47) with ischemic cardiomyopathy (mean LVEF +/- SD, 30% +/- 6%) undergoing surgical revascularization were studied with 18F-FDG SPECT to assess viability. Regional and global function were measured before and 3-6 mo after revascularization. Heart failure symptoms were graded according to the New York Heart Association (NYHA) criteria, before and 3-6 mo after revascularization. RESULTS: The number of viable segments per patient was directly related to the improvement in LVEF after revascularization (r = 0.79, P < 0.01). Receiver operating characteristic curve analysis revealed that the cutoff level of four viable segments (representing 31% of the left ventricle) yielded the highest sensitivity and specificity (86% and 92%, respectively) for predicting improvement in LVEF. Furthermore, the presence of four or more viable segments predicted improvement in heart failure symptoms after revascularization, with positive and negative predictive values of 76% and 71%, respectively. CONCLUSION: The presence of substantial viability (four or more viable segments, 31% of the left ventricle) on FDG SPECT is predictive of improvement in LVEF and heart failure symptoms postoperatively. PMID- 11197986 TI - Does CABG improve left ventricular ejection fraction in patients with ischemic cardiomyopathy, and does it matter? PMID- 11197987 TI - Glucose metabolism of breast cancer assessed by 18F-FDG PET: histologic and immunohistochemical tissue analysis. AB - Breast cancer is characterized by elevated glucose consumption resulting in increased uptake of 18F-FDG. However, tracer uptake varies considerably among tumors imaged with PET. This study compared histologic and immunohistochemical tissue analysis of breast carcinomas with preoperative FDG uptake assessed by PET to identify tumor characteristics that define the degree of tracer accumulation. METHODS: FDG uptake in breast tumors was quantified by calculating standardized uptake values (SUVs) corrected for partial-volume effect and normalized to blood glucose level at the time of tracer injection. The histologic sections of 50 invasive and 6 noninvasive breast carcinomas were analyzed for histologic type, microscopic tumor growth pattern, percentage of tumor cells, presence of inflammatory cells, density of blood vessels, histopathologic grading, tumor cell proliferation (mitotic rate and antibody binding of MIB-1), expression of estrogen and progesterone receptors, and expression of the glucose transporter protein Glut-1. RESULTS: A positive correlation was found between FDG uptake and histologic tumor type (ductal vs. lobular; P = 0.003), microscopic tumor growth pattern (nodular vs. diffuse; P = 0.007), and tumor cell proliferation (MIB-1; P = 0.009). Tumors with diffuse growth patterns had significantly lower SUVs compared with clearly defined tumors. A weak relationship was found between FDG uptake and the percentage of tumor cells (P = 0.06). Lower densities of blood vessels corresponded to higher FDG uptakes (P = 0.08). However, even significant correlations showed poor correlation coefficients. No relationship was found between FDG uptake and the following: tumor size; axillary lymph node status; percentage of necrotic, fibrotic, and cystic compounds; presence of inflammatory cells; steroid receptor status; and expression of Glut-1. CONCLUSION: Histologic and immunohistochemical tissue analysis was unable to sufficiently explain the variation of FDG uptake in breast cancer. The degree of metabolic changes after malignant transformation is most likely explained by a complex interaction between cellular energy demand and tumoral microenvironment. Therefore, FDG PET imaging may not be used to estimate tumor biologic behavior of breast cancer such as differentiation, histopathologic grading, cell proliferation, or axillary lymph node status. PMID- 11197988 TI - Renal cortical scintigraphy and diuresis renography in infants and children. AB - Renal scintigraphy is performed frequently in infants and children. Renal cortical scintigraphy using 99mTc dimercaptosuccinic acid is predominantly performed to assess the renal sequelae of urinary tract infection. It is most commonly performed for the evaluation of chronic renal scars, although it is also undertaken in the assessment of acute pyelonephritis. Diuresis renography using 99mTc mercaptoacetyltriglycine is of great use in the evaluation of renal tract obstruction, which may occur at a variety of levels, but most commonly occurs at the ureteropelvic junction. Consensus statements have been formulated in an attempt to standardize methods of performing these investigations. However, several areas of controversy exist in the performance of these studies, and these are outlined. Radionuclide cystography and renal function estimation using clearance calculations are not covered in this article. PMID- 11197989 TI - 8-[18F]Fluoropenciclovir: an improved reporter probe for imaging HSV1-tk reporter gene expression in vivo using PET. AB - We have synthesized and evaluated 8-[18F]fluoropenciclovir (FPCV) and compared it with 8-[18F]fluoroganciclovir (FGCV) for monitoring the expression of herpes simplex virus type 1 thymidine kinase (HSV1 -tk) reporter gene in cell culture and in vivo. METHODS: C6 rat glioma cells stably transfected with HSV1-tk (C6-stb tk+) and control C6 cells were evaluated for their ability to accumulate FGCV versus FPCV. For in vivo studies, 15 mice were injected by tail vein with increasing levels of an adenoviral vector carrying HSV1-tk. Forty-eight hours later the mice were injected with FPCV and killed 3 h later. The percentage injected dose per gram (%ID/g) liver was then determined. Two additional mice were studied by microPET and autoradiography using FPCV to image adenoviral mediated hepatic HSV1-tk reporter gene expression. A tumor-bearing mouse (C6 control and C6-stb-tk+) was imaged with FDG, FGCV, and FPCV. Two mice carrying tumors expressing two different reporter genes, HSV1-tk and dopamine type 2 receptor (D2R), were also imaged by microPET using FPCV (day 1) and 3-(2' [18F]fluoroethyl)spiperone (FESP) (day 2). RESULTS: FPCV shows a significantly greater accumulation in C6-stb-tk+ cells than does FGCV (P < 0.05). Over identical ranges of adenoviral administration, mouse liver shows a higher %ID/g liver for FPCV (0%-9%) compared with our previously reported results with FGCV (0%-3%). In C6 control and C6-stb-tk+ tumor-bearing mice, FPCV has a greater accumulation than does FGCV for equal levels of HSV1-tk gene expression. In mice carrying tumors expressing either HSV1-tk or D2R reporter genes, there is a corresponding retention of FPCV and FESP, respectively. CONCLUSION: These results indicate that FPCV is a better reporter probe than is FGCV for imaging lower levels of HSV1 -tk gene expression in vivo. The results also reveal the ability to monitor the expression of two distinct reporter genes in the same animal using reporter probes specific for each gene. PMID- 11197990 TI - Update on investigation of Ritalin conspiracy. PMID- 11197991 TI - Fluvoxamine approved for treating OCD in children. PMID- 11197992 TI - PMS and PMDD in the domain of mental health nursing. AB - Premenstrual syndrome (PMS) is a complex cluster of symptoms that occurs 7 to 14 days prior to menses and ends 1 to 2 days after menses. Premenstrual syndrome symptoms can create severe, debilitating psychological and physical problems. The Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) provides criteria for premenstrual dysphoric disorder (PMDD), which can be considered the most severe presentation on the PMS continuum. A critical part of determining the diagnosis is evaluating the timing of symptoms. True PMS only occurs during the luteal phase of the menstrual cycle, with a symptom-free period during the follicular phase. After identifying a diagnosis of PMS or PMDD, the first-line treatment of these symptom clusters continues to be lifestyle changes, including stress management, healthy diet, regular aerobic exercise, cognitive behavioral therapy, and fortified coping strategies. Women whose symptoms are not controlled adequately with lifestyle modifications may benefit from medications. Possible medication recommendations include selective serotonin re-uptake inhibitors (SSRIs), diuretics, gonadotropin-releasing hormone (GnRH) agonists, and vitamin and mineral supplements. PMID- 11197993 TI - Role conflicts & coping strategies in caregiving. A symbolic interactionist view. AB - Institutional health care delivery is characterized by interdependency among caregivers and between caregivers and care receivers, which leads to role conflicts. This article examines role conflicts and coping strategies of health care aides who are faced with differing expectations of RNs and residents. Guided by a symbolic interactionist perspective, ethnographic data from 12 RNs, 15 health care aides, and 32 nursing home residents of Italian-Catholic and Anglo Saxon descent in Toronto, Ontario, Canada, was gathered. Results showed that health care aides differed in how they handled role conflict and their elderly clients' concerns. Health care aides were more likely to reject conflicting role expectations from residents than from RNs. PMID- 11197994 TI - Scope of practice issues in forensic nursing. AB - 1. There is significant role variation, across the Western world, in relation to how forensic nurses practice. 2. The authors conducted a pilot survey of forensic nurses in Australia, New Zealand, the United States, and the United Kingdom to examine forensic nursing practice, role definition, and role boundaries. 3. Issues arising from the data include the visibility of forensic nurses, the client group, forensic-specific education, and role development. PMID- 11197995 TI - How people with schizophrenia build their hope. AB - 1. Both clinicians and consumers identified the importance of maintaining relationships and experiencing success as helpful in building and nurturing hope for consumers. 2. To provide holistic care, clinicians need to discuss spirituality and meaning with clients. 3. Because being hopeful is an active process, clinicians need to talk to clients about hope, openly, realistically, and strategically. PMID- 11197996 TI - The way it is, was, and will be. PMID- 11197997 TI - [Nanobacteria as a cause of renal diseases and vascular calcifying pathology in renal patients ("endovascular lithiasis"]. PMID- 11197998 TI - [Varicella pneumonia in the adult: study of 22 cases]. AB - BACKGROUND: Retrospective study of the varicella pneumonia in adults with clinical, therapeutic and evolutive features in 22 patients in the last 5 years. MATERIAL AND METHODS: The diagnosis was established by clinical and radiologic criteria in the course of varicella infection. The antecedents of pregnancy, smoking habit, previous contact with patients with varicella and underlying disease were evaluated. RESULTS: Twenty-two patients (14 males and 8 women: mean age 31 years. range: 22-40) were included in the study. None of them were immunocompromised, 16 (72.7%) have had previous contact with varicella patients. 19 (86.3%) were heavy smokers and none of the female patients was pregnant. All patients had fever and exanthem, cough had 20 (90.9%) dyspnea 16 (72.7%), chest pain 9 (40.9%) and hemoptysis 5 (22.7%). Only two patients showed pO2 < 60 mmHg. Chest X-ray revealed an interstitial pattern in 14 cases (63.3%), and micronodular in 8 (36.3%). All patients received treatment with intravenous acyclovir. Three patients (13.6%) were admitted to the Intensive Care Unit due to respiratory insufficiency, needing mechanical ventilation one of them (4.5%). Another three developed failure renal reversible associated with acyclovir. All patients had a favourable clinical course. CONCLUSIONS: We believe, that early, aggressive use of intravenous acyclovir in adult varicella pneumonia may be lifesaving, preventing progressive respiratory failure and reducing the high mortality rate of the disease. Therapy with corticosteroids should be considered in addition to antiviral therapy in patients with severe varicella pneumonia. While oral acyclovir chemoprophylaxis is probably beneficial in populations with chicken pox. PMID- 11197999 TI - [Epidemiologic study of infection by hepatitis C virus in a hemodialysis unit]. AB - OBJECTIVE: To analyze the prevalence of infection, the frequency of HCV genotypes and the epidemiology characteristics among the patients in hemodialysis treatment in one 25 years old hospital hemodialysis center and one 15 years old secondary unit by a transversal cross-section study in 1998. PATIENTS AND METHODS: 171 hemodialyzed-patients were studied. Patients sera were analyzed by the presence of HCV antibodies anti-VHC by a enzymoimmunoassay (Abbott Cientifica) and the presence of antibodies was confirmed by a line immunoassay (Inno-LIA HCV AbIII) and by the presence of VHC-RNA by reverse transcriptase PCR (Cobas Amplicor HCV). Genotypes were determinate by reverse hybridization (Inno-LIA HCV III). RESULTS: Fifty (29.2%) of the patients were HCV antibody positive. Forty-five (26.3%) were HCV-RNA positive, all of them with antibodies positive. The distribution of genotypes was: 1b, 34 (75.5%); 4f, 4 (8.9%); 1a, 3 (6.7%); 1, 3 (6.7%) and 1 case could not be typed (2.2%). In 14 patients (28.0%), seroconversions were documented Twenty-one patients (42.0%) were diagnosed when the routine tests were available and 15 patients (30.0%) were diagnosed pre-dialysis. The multivariate analysis showed that the risk of HCV infection was greater for patients who had been more 8 years on dialysis (OR: 6.22; 95% CI: 1.24-31.07). CONCLUSIONS: Data presented indicate that the prevalence of HCV infections in our hemodialysis units and the number of seroconversions were high and the HCV subtype 1b was more frequent; because of this, the screening by both serological and molecular methods is necessary, at least twice a year, to identify all the infected patients. Besides, we think that is necessary to increase the control of the completion of the Universal Precautions. PMID- 11198000 TI - [False resistance to imipenem in gram negative bacilli with and automatized system]. AB - BACKGROUND: The aim of this study was to evaluate the reliability of MIC values of imipenem against gramnegative rods obtained with the automated system WalkAway 98 (MicroScan, Dade, USA). MATERIAL AND METHODS: One-hundred and seventy three consecutive clinical isolates of Gram-negative rods for which the MIC of imipenem were > or = 4 mg/l (Urine-Combo 6I panels, U6I) or > or = 8 mg/l (Neg-Combo 6I panels, N6I) were evaluated, including 104 non-fermenting gram-negative rods (NFGNR) and 69 enterobacteria. Panels were inoculated and read according to manufacturer's instructions. Microdilution, according to NCCLS guidelines, was used as the method of reference. MIC of imipenem determined by WalllAway-96 and microdilution differing > or = 2 dilution steps from those obtained with mirodilution were considered as discrepant results. Discrepancies in clinical categories were also evaluated by calculating three types of errors: very major (false susceptibility), major (false resistance) and minor (either susceptible or resistant by one method and intermediate by the other one). RESULTS: The percentages of discrepancies in the MIC of imipenem determined with U6I panels were 74% and 84% for NFGNR and enterobacteria, respectively. No very major errors were detected. Major errors were observed for 6% and 12% of the strains with U6I panels in NFGNR and enterobacteria, respectively, and in 12% (NFGNR) and 50% (enterobacteria) with N61 panels. With U61 panels minor errors were observed in 11% and 25% of NFGNR and enterobacteria, respectively, while with N61 panels minor error were observed in 39% and 45% of both groups, respectively. CONCLUSIONS: MIC of imipenem > or = 4 mg/l obtained with the WalkAway-96 system against gramnegative rods, particularly in the case of enterobacteria, should be confirmed with a reference susceptibility method. PMID- 11198001 TI - [Presence of conjugative transposon Tn1545 in strains of Streptococcus pneumoniae with mef(A), erm(B), tet(M), catpC194 and aph3'-III genes]. AB - We studied the association of MLS resistance genes (erm(B) and mef(A) with others non-MLS resistance genes: tet(M) (tetracycline and minocycline), catpC194 (chloramphenicol) and aph3'-III (kanamycin) in order to know how is selected the multiresistant in Streptococcus pneumoniae. The tet(M) and catpC194 genes were present very often in the pneumococci with the erm(B) gene but the aph3'-III was found only in four strains. Tn1545 was nearly always the responsible for the dissemination of these genes. In contrast, mef(A) was not associated with tet(M) and and catpC194 and is disseminated in a different conjugative transposon. The linkage of multiple antibiotic resistance genes on the same mobile element is of importance for public health, because the use of one antibiotic selects for the transposon which carries multidrug resistance genes. PMID- 11198002 TI - [Serologic response against hepatitis C virus as a predictive factor to the treatment with interferon]. AB - AIM: Serologic response of patients with chronic hepatitis C (CHC) was studied as a predictor of response to IFN therapy and we evaluated the correlation between such response with gender, risk factor, serum ferritin, GGT, Knodell's index and fibrosis. MATERIALS AND METHODS: A study was carried out in 40 patients with CHC who were treated with interferon-alpha 3 MU 3 times weekly 48 weeks. The diagnosis of hepatitis C was made based upon Inmuno-Blot (core, NS3, NS4 y NS5) and confirmed by detection of HCV-RNA in serum. Responses were evaluated (normal ALT and undetectable HCV-RNA in serum) at three months, at the end of treatment and six months after treatment. RESULTS: No significant differences were observed in responses at three months with regard to gender (47% males responded versus 55% females, n.s.), source of infection (50% intravenous drug users versus 50% non intravenous drug users; n.s.) and GGT level (50% with high levels versus 50% with normal levels, n.s.); however 25% of patients with high level of serum iron responded versus 59% with normal values (p = 0.04) and 28% of patients with fibrosis at liver histopathology responded versus 82% without fibrosis (p = 0.0006). No differences were observed at the response rates with regard to levels of core (20.1 SD:4 versus 19.5 SD:2.2, n.s.), NS3 (18.6 SD:7 versus 17.1 SD:7.3, n.s.) and NS4 (14.3 SD:7.7 versus 10.5 SD:9.2, n.s.). However NS5 levels in responders were 2.5 (0-16) versus 5.2 (0-16.5) in nonresponders (p < 0.05) and score in Knodell's index was 6.1 SD:2.6 in responders versus 9.2 SD:2.4 in nonresponders (p = 0.006). 47% of responders relapsed 6 months after the end of treatment with IFN. CONCLUSIONS: Titers of anti-NS5 showed predictive value of response as opposed to anti-core, anti-NS3 and anti-NS4 and it may justify its determination in the assessment of a patient with CHC at centers without capacity for measuring genotype and viral load. Low level of serum iron and Knodell's index like absence of fibrosis at liver histopathology were also variables with predictive value of response, as opposed to gender, GGT level and source of infection. PMID- 11198003 TI - [Varicella vaccine. An immunization of the child and the adult]. PMID- 11198004 TI - [Hepatic lesions after cholecystectomy for cholelithiasis]. PMID- 11198005 TI - [Inflammatory cutaneous nodules in an immunodepressed patient]. PMID- 11198006 TI - [Cavitary pulmonary cryptococcosis in a patient with AIDS]. PMID- 11198007 TI - [Pseudomonas aeruginosa in a patient splenectomized for non-Hodgkin's lymphoma]. PMID- 11198008 TI - [Aggressive acute endocarditis caused by Staphylococcus lugdunensis complicated with multiple cerebral septic emboli]. PMID- 11198009 TI - [Diagnosis of tuberculous arthritis from the isolation of Mycobacterium tuberculosis in blood agar and chocolate agar]. PMID- 11198010 TI - [Corporal distribution of infections caused by herpes simplex virus types 1 and 2]. PMID- 11198011 TI - [Parenteral antibiotic treatment and hospital based home care units. The current situation]. PMID- 11198012 TI - [levofloxacin and behavior disorder in a patient admitted to intensive care]. PMID- 11198013 TI - [Milk auto-inoculation as an exceptional cause of fever of unknown origin]. PMID- 11198014 TI - Routine DNA analysis based on 12S rRNA gene sequencing as a tool in the management of captive primates. AB - Automated DNA sequencing of a fragment of the relatively slowly evolving mitochondrial 12S rRNA gene was used to distinguish primate species, and the method was compared with species determination based upon classical taxonomy. DNA from blood from 53 monkeys housed at the Stichting AAP Shelter for Exotic Animals, all Old World monkeys, was amplified by polymerase chain reaction (PCR) with a primer set spanning approximately 390 nucleotides of the mitochondrial 12S rRNA gene. The products were directly sequenced and compared with our database of primate 12S sequences. Many individuals were found to harbor a 12S sequence identical to one of the reference sequences. For others, phylogenetic methods were used for species estimation, which was especially informative in Cercopithecus species. PMID- 11198015 TI - Nosocomial transmission of Mycobacterium tuberculosis from an extrapulmonary site. AB - OBJECTIVE: To assess the extent of nosocomial transmission and risk factors associated with tuberculin skin test (TST) conversions among healthcare workers (HCWs) exposed to a patient with genitourinary Mycobacterium tuberculosis. DESIGN: Retrospective cohort study of exposed HCWs. SETTING: A 275-bed community hospital in Middle Tennessee. PARTICIPANTS: A total of 128 exposed HCWs and the index patient, who required drainage of a prostatic abscess and bilateral orchiectomy and expired after a 27-day hospitalization. Disseminated tuberculosis was diagnosed at autopsy. METHODS: Contact tracing was performed on exposed HCWs. Logistic regression was used to identify independent risk factors associated with TST conversion. RESULTS: A total of 128 HCWs were exposed to the index patient. There was no evidence of active pulmonary tuberculosis throughout the patient's hospitalization; TST conversions occurred only among HCWs who were exposed to the patient during or after his surgical procedures. A total of 12 (13%) of 95 exposed HCWs who were previously nonreactive had newly positive TST: 6 of 28 nurses, 3 of 3 autopsy personnel, 2 of 17 respiratory therapists, and 1 of 12 surgical staff. By logistic regression, irrigation or packing of the surgical site was the only independent risk factor associated with TST conversion among nurses (odds ratio, 9; 95% confidence interval, 1.2-67; P=.03). CONCLUSION: Manipulation of infected tissues of the genitourinary tract can result in nosocomial transmission of tuberculosis. PMID- 11198016 TI - An outbreak of scabies in a teaching hospital: lessons learned. AB - OBJECTIVE: To investigate an outbreak of scabies in an inner-city teaching hospital, identify pathways of transmission, institute effective control measures to end the outbreak, and prevent future occurrences. DESIGN: Outbreak investigation, case-control study, and chart review. SETTING: Large tertiary acute-care hospital. RESULTS: A patient with unrecognized Norwegian (crusted) scabies was admitted to the acquired immunodeficiency syndrome (AIDS) service of a 940-bed acute-care hospital. Over 4 months, 773 healthcare workers (HCWs) and 204 patients were exposed to scabies. Of the exposed HCWs, 147 (19%) worked on the AIDS service. Risk factors for being infested with scabies among HCWs included working on the AIDS service (odds ratio [OR], 5.3; 95% confidence interval [CI95], 2.17-13.15) and being a nurse, physical therapist, or HCW with extensive physical contact with infected patients (OR, 4.5; CI95, 1.26-17.45). Aggressive infection control precautions beyond Centers for Disease Control and Prevention barrier and isolation recommendations were instituted, including the following: (1) early identification of infected patients; (2) prophylactic treatment with topical applications for all exposed HCWs; (3) use of two treatments 1 week apart for all cases of Norwegian scabies; (4) maintaining isolation for 8 days and barrier precautions for 24 hours after completing second treatment for a diagnosis of Norwegian scabies; and (5) oral ivermectin for treatment of patients who failed conventional therapy. CONCLUSIONS: HCWs with the most patient contact are at highest risk of acquiring scabies. Because HCWs who used traditionally accepted barriers while caring for patients with Norwegian scabies continued to develop scabies, we found additional measures were required in the acute-care hospital. HCWs with skin exposure to patients with scabies should receive prophylactic treatment. We recommend (1) using heightened barrier precautions for care of patients with scabies and (2) extending the isolation period for 8 days or 24 hours after the second treatment with a scabicide for those patients with Norwegian scabies. Oral ivermectin was well tolerated for treating patients and HCWs who failed conventional treatment. Finally, we developed a surveillance system that provides a "barometric measure" of the infection rate in the community. If scabies increases in the community, a tiered triage system is activated to protect against transmission among HCWs or hospital patients. PMID- 11198017 TI - An evaluation of hospital special-ventilation-room pressures. AB - OBJECTIVE: To quantitate the magnitude and consistency of positive (airflow out) and negative (airflow in) hospital special-ventilation-room (SVR) airflow. DESIGN: A room-pressure evaluation was conducted during two seasons on a total of 18 rooms: standard rooms, airborne infection isolation rooms, and protective environment rooms. The pressures were measured using a digital pressure gauge piezoresistive pressure sensor that measured pressure differentials. With doors closed, the rooms were measured a minimum of 30 times each for a cooling season and a heating season. RESULTS: The standard rooms showed the least amount of variability in pressure differential, with an average of -0.2 Pa (median, -0.2 Pa), and an interquartile range (IQR) of 0.4 Pa. Airborne infection isolation rooms showed more variability in pressure, with an average of -0.3 Pa (median, 0.2 Pa) and an IQR of 0.5 Pa. Protective environment rooms had the greatest fluctuation in pressure, with an average of 8.3 Pa (median, 7.7 Pa) and an IQR of 8.8 Pa. Dramatic pressure changes were observed during this evaluation, which may have been influenced by room architectural differences (sealed vs unsealed); heating, ventilation, and air-conditioning zone interactions; and stack effect. CONCLUSION: The pressure variations noted in this study, which potentially affect containment or exclusion of contaminants, support the need for standardization of pressure requirements for SVRs. To maintain consistent pressure levels, creating an airtight seal and continuous pressure monitoring may be necessary. PMID- 11198018 TI - Epidemiology of surgical-site infections diagnosed after hospital discharge: a prospective cohort study. AB - OBJECTIVE: To study postoperative infections in hospital and after discharge, and to identify the risk factors for such infections. DESIGN: Prospective cohort study, with telephone follow-up for 1 month after hospital discharge. SETTING: The general surgery service of a tertiary hospital in Spain. MAIN OUTCOME MEASURE: In-hospital and postdischarge surgical-site infection (SSI), always confirmed by a physician. RESULTS: Of the 1,506 patients initially enrolled, 29 died during hospital stay, and 33 were lost to postdischarge follow-up. An SSI was identified prior to discharge in 123 patients and after discharge in 103. For several variables (age, serum albumin, glycemia, lengths of preoperative and postoperative hospital stay, etc), there were no differences between patients with postdischarge SSI and noninfected patients; however, there were differences detected between patients with postdischarge SSI and in-hospital SSI, as well as between patients with in-hospital SSI and noninfected patients. The analysis of risk factors showed that most predictors for in-hospital SSI did not behave in the same manner for postdischarge SSI. Stepwise logistic regression only identified chemoprophylaxis, age (advanced age was a preventive factor), and body mass index as independent risk factors for postdischarge SSI. Differences in risk factors between in-hospital and post-discharge SSIs remained even after controlling for time from operation to diagnosis. CONCLUSIONS: Most predictors of in-hospital SSI were not predictors of postdischarge SSI. PMID- 11198019 TI - Converting incidence and prevalence data of nosocomial infections: results from eight hospitals. AB - OBJECTIVE: To investigate the use of the formula of Rhame and Sudderth for the interconversion of prevalence and incidence data on the frequency of nosocomial infections. DESIGN: Comparison of observed and calculated incidence data and prevalence data. SETTING: One 8-week incidence investigation in the surgical and intensive care units of eight medium-sized hospitals; three separate point prevalence studies in the same units. RESULTS: The overall prevalence observed after the three prevalence studies in 2,169 patients was 6.8% (95% confidence interval [CI95], 5.7-8.0). In 2,882 discharged patients observed during the incidence study, the mean hospitalization was 9.8 days; patients with one or more nosocomial infection had a mean hospitalization time of 22.3 days and a mean interval of 8.2 days from admission to the first day of infection. Based on these data, the overall calculated incidence was 4.7%, whereas the observed incidence was 4.3% (CI95, 3.6-5.2). Vice versa, an overall prevalence of 6.2% was found when calculated from the observed incidence data. The incidence data calculated from prevalence data also were within the confidence interval of the incidences observed for urinary tract infections and surgical-site infections. (However, it was not possible to convert the data for two of the eight hospitals.) CONCLUSION: The approximate mathematical relationship between the prevalence and incidence data of nosocomial infection is confirmed by this study. However, although it is theoretically possible, we would not recommend the conversion of prevalence into incidence data or vice versa. PMID- 11198020 TI - An outbreak of imipenem-resistant Acinetobacter baumannii in critically ill surgical patients. AB - OBJECTIVE: To describe an outbreak of imipenem-resistant Acinetobacter baumannii (IR-Ab) and the measures for its control, and to investigate risk factors for IR Ab acquisition. DESIGN: An observational and a case-control study. SETTING: A surgical intensive care unit (ICU) in a university tertiary care hospital. METHODS: After admission to the ICU of an IR-Ab-positive patient, patients were prospectively screened for IR-Ab carriage upon admission and then once a week. Environmental cleaning and barrier safety measures were used for IR-Ab carriers. A case-control study was performed to identify factors associated with IR-Ab acquisition. Cases were patients who acquired IR-Ab. Controls were patients who were hospitalized in the ICU at the same time as cases and were exposed to IR-Ab for a similar duration as cases. The following variables were investigated as potential risk factors: baseline characteristics, scores for severity of illness and therapeutic intervention, presence and duration of invasive procedures, and antimicrobial administration. RESULTS: Beginning in May 1996, the outbreak involved 17 patients over 9 months, of whom 12 acquired IR-Ab (cases), 4 had IR Ab isolates on admission to the ICU, and 1 could not be classified. Genotypic analysis identified two different IR-Ab isolates, responsible for three clusters. Ten of the 12 nosocomial cases developed infection. Control measures included reinforcement of barrier safety measures, limitation of the number of admissions, and thorough environmental cleaning. No new case was identified after January 1997. Eleven of the 12 cases could be compared to 19 controls. After adjustment for severity of illness, a high individual therapeutic intervention score appeared to be a risk factor for IR-Ab acquisition. CONCLUSION: The outbreak ended after strict application of control measures. Our results suggest that high work load contributes to IR-Ab acquisition. PMID- 11198021 TI - Increase in hand-alcohol consumption among medical staff in a general hospital as a result of introducing a training program and a visualization test. AB - To assess the impact of training programs, including a visualization test for hand disinfection, we monitored the hand-alcohol consumption of medical staff. The consumption increased steadily from 5.7 L of hand alcohol per capita per year in 1990 to 9.1 L in 1998. There was no significant increase in skin problems. PMID- 11198022 TI - Clostridium difficile-associated diarrhea in a VA medical center: clustering of cases, association with antibiotic usage, and impact on HIV-infected patients. AB - A case-control study of patients with stools assayed for Clostridium difficile toxin over a 24-month period at a Veterans Affairs hospital found that the majority of cases (70.6%) occurred in temporal clusters. Clustering was particularly evident on a designated human immunodeficiency virus (HIV) unit. Thirty-four (75.5%) of 45 HIV-infected patients with C difficile-associated diarrhea (CDAD) died during their hospitalization. Third-generation cephalosporins were the antibiotics most strongly associated with CDAD. PMID- 11198023 TI - Invasive aspergillosis outbreak on a hematology-oncology ward. AB - An outbreak of invasive aspergillosis occurred in a community hospital in temporal association with construction activity. Epidemiological investigation showed that patients who are at highest risk comprise a small group and are readily identifiable. Clinicians should strive to protect these patients, following guidelines published by the Centers for Disease Control and Prevention. PMID- 11198024 TI - A nosocomial outbreak of multiresistant Acinetobacter baumannii originating from an intensive care unit. AB - An outbreak of a multiresistant Acinetobacter baumannii in February through September 1996 affected 103 patients in a regional hospital in Singapore. We describe the effectiveness of closure of the outbreak area and the importance of good teamwork in the management of the outbreak. PMID- 11198025 TI - Tap water colonization with Pseudomonas aeruginosa in a surgical intensive care unit (ICU) and relation to Pseudomonas infections of ICU patients. AB - Water faucets on a surgical intensive care ward were examined prospectively as a source of Pseudomonas aeruginosa infections. All water outlets harbored distinct genotypes of P aeruginosa over prolonged time periods. Over a period of 7 months, 5 (29%) of 17 patients were infected with P aeruginosa genotypes also detectable in tap water. PMID- 11198026 TI - Management of occupational exposures to hepatitis C virus: current practice and controversies. AB - Unlike hepatitis B virus and human immunodeficiency virus, there currently are no immunization or chemoprophylactic interventions available to prevent infection after an occupational exposure to hepatitis C virus (HCV). A "Reality Check" session was held at the 4th Decennial International Conference on Nosocomial and Healthcare-Associated Infections to gather information on current practices related to management of occupational exposures to HCV, generate discussion on controversial issues, and identify areas for future research. Infection control professionals in attendance were knowledgeable in most issues addressed regarding the management of occupational exposures to HCV. Areas of controversy included the use of antiviral therapy early in the course of HCV infection and the appropriate administrative management of an HCV-infected healthcare worker. PMID- 11198027 TI - The rocky road: qualitative research as evidence. PMID- 11198028 TI - Cervical screening: quality assurance developments in Europe. PMID- 11198029 TI - Organ sparing management for carcinoma of the vulva & vagina. PMID- 11198030 TI - Minimizing morbidity from radical abdominal hysterectomy. PMID- 11198031 TI - Controversies in surgical management of advanced ovarian cancer (stage III-IV). PMID- 11198032 TI - Endometrial carcinoma. Is routine intensive periodic follow-up of value? PMID- 11198034 TI - Solitary metastasis to the uterine cervix from the early gastric cancer: a case report. AB - Metastasis of gastric cancer to the uterine cervix is rare, and a case of metastasis to the uterine cervix from early gastric cancer has never before been reported. We here present a patient who underwent a gastrectomy due to asymptomatic early gastric cancer found by chance and who subsequently suffered from a solitary metastasis to the uterine cervix from the primary early gastric cancer. Similar to Krukenberg tumors of the ovary, lymphatic dissemination is regarded as the route of metastasis from the stomach to the uterine cervix. We surmise that the present metastasis occurred through the lymphatic channel because lymph vessel permeations were found in both the primary lesion of the stomach and the metastatic lesion of the uterine cervix. PMID- 11198033 TI - Radical abdominal versus laparoscopic hysterectomy for stage IB cervical cancer: what's the point? AB - OBJECTIVE: To evaluate surgical morbidity and length of stay for type III radical abdominal hysterectomy performed in the private practice setting, and to compare these results with currently available data on laparoscopic radical hysterectomy. METHODS AND MATERIALS: One hundred seventy-five consecutive type III radical abdominal hysterectomies performed by the author in a uniform fashion over a ten year period for patients with stage IB cervical cancer were evaluated. All surgeries were performed in private community hospitals in New Jersey. RESULTS: Type III radical abdominal hysterectomy performed in the private setting using the author's protocol resulted in lower surgical morbidity, equivalent hospital stay and resumption of normal activities, and much shorter operating times than laparoscopic radical hysterectomy. CONCLUSION: Laparoscopic radical hysterectomy provides no surgical or financial advantage over radical abdominal hysterectomy when the latter is performed in the private practice setting; results from laparoscopic surgery are inferior with respect to morbidity. PMID- 11198035 TI - Intraoperative gold grain implants for pelvic wall recurrences of various malignancies: toxicity, results, and failure analysis in 37 patients. AB - PURPOSE: We conducted this study to determine the complications and long-term results of intraoperative gold-grain implants as therapy for pelvic wall recurrences of various malignancies. MATERIALS AND METHODS: We retrospectively analyzed complications and long-term results of intraoperative radioactive 198Au gold grain implants of 4-mc radon equivalent in 37 patients with pelvic wall recurrences of various malignancies treated at the University of Texas M. D. Anderson Cancer Center. The estimated dose was 30-100 Gy, which was increased to 100-120 Gy plus external-beam irradiation if the dose to the tumor volume was too low. All patients had follow-up of 4 months to 12 years. Of the 37 patients, 34 had lower leg edema, 22 had lower limb pain, and 22 had ureteral obstruction. RESULTS: Six of 34 patients with lower limb pain had partial relief and nine had complete relief. Of 22 patients with ureteral obstruction, ten had complete resolution and four had partial relief. Lower limb edema was improved in 16 of 22 patients. Of the 37 patients studied, 14 are alive and 23 have died. CONCLUSION: In selected patients, gold grain implantation to a dose of 70-100 Gy relieved some symptoms of unresectable pelvic wall recurrences of various malignancies. We believe that intraoperative gold grain implants appear to be the only useful treatment for patients with recurrent malignancies fixed to the pelvic wall and provide these patients with better and longer palliation and a good quality of life. PMID- 11198036 TI - Nuclear grading of endometrial cancer harbors heterogenous prognostic groups as detected by proliferation activity. AB - OBJECTIVE: Nuclear grading, in addition to the histopathological result of every tumor, is responsible for consecutive treatment designs. Ki-S5 is the monoclonal antibody against a formalin-resistant epitope of the Ki-67 antigen and can be determined in paraffin-embedded samples. The aim of the study was a comparative analysis of the nuclear grading of endometrial cancer and the proliferation marker Ki-S5. METHODS: In 126 specimens of endometrial cancer the proliferation activity of the monoclonal antibody Ki-S5 was determined (streptavidin-biotin complex method) in correlation to nuclear grading. In the group of grade 2, stages Ib and Ic andenocarcinomas, proliferation rates were compared to recurrence rates. RESULTS: Divergent proliferation rates resulted. Adenoacanthomas showed a relatively low proliferation rate (<28%). For the andenosquamous carcinomas the proliferation rate ranged between 28-43%. The largest group of adenocarcinomas showed proliferation rates from 5-74%. A clear dependency between increasing proliferation rates and decreasing differentiation (nuclear grading 2-3) was observed. In the small group of patients with andenocarcinomas, nuclear grading G2 stages Ib and Ic, 38 suffered no recurrence after 6-10 years. However, the six patients with proliferation rates of over 35% all suffered a recurrence. CONCLUSIONS: The results emphasize the need to differentiate G2 tumors, depending on their proliferation rate, into low risk (KiS5<35%) and high risk cases (Ki-S5>35%). PMID- 11198037 TI - Prognostic value of protein p53 and ki-67 in invasive vulvar squamous cell carcinoma. AB - The aim of this research was to detect new valid prognostic indicators that allow us to choose the best therapy and follow-up for patients with a poor prognosis. One hundred and twenty-nine patients with invasive squamous carcinoma of the vulva treated at the Gynecology Clinic of the University of Padua between January 1, 1975 and December 31, 1999 have been evaluated: Protein p53 and ki-67 were studied by immunohistochemical investigations and their prognostic significance was evaluated. The relation with the classic clinico-pathological prognostic factors was also studied. The results showed a close association between tissue overexpression of the two proteins and clinico-pathological characteristics of the aggressivity of the neoplasm. Moreover, the group of positive p53 patients with a diffuse distribution pattern of ki-67 resulted in having a somewhat shorter survival with respect to the groups with negative p53 and/or a focal pattern. Such negative prognostic significance was confirmed by the results of the multivariate analysis performed with the Cox model which shows that patients with p53 positive values and a diffuse pattern have a higher relative risk of death compared to patients with p53 negative values and focal pattern (p=0.0001). The statistical significance of the prognostic value of the association of p53 and ki-67 thus seems to give these two factors greater weight with respect to the others we investigated. PMID- 11198038 TI - Diagnostic reliability of prebioptic methods in the prediction of a histological basis of cervical lesions and its correlation with accuracy of colposcopically directed biopsy in patients with cervical neoplasia. AB - OBJECTIVE: High incidence of cervical cancer in the Czech Republic leads us to look for an optimal model of screening. The evaluation of the realiability of prebiopsy (cytology and colposcopy) and of punch biopsy is an important diagnostic step. MATERIAL AND METHODS: In a prospective study we examined 308 women detected by cytological screening who afterwards underwent surgery for a cervical lesion. Punch biopsy before the operation, most frequently by conization, was performed in every patient after assessing the prebioptic prediction (colposcopy and cytology). RESULTS: Reliable cytological screening associated with good colposcopy permits a correct diagnosis with high reliability. The rate of errors which increase the risk (threatening of health or the life of women) was 2.9% by prebioptic methods (high reliability) and 4.4% by punch biopsy. CONCLUSION: These good results are achieved in centers led by trained physicians and experts in cytology and skilled in colposcopy. PMID- 11198039 TI - Management of lymphocysts after cervical carcinoma surgery. AB - In the Gynecological Clinic of the Oncological National Center of Georgia from 1964 to 1999 1,805 extended hysterectomies due to carcinoma of the cervix uteri were performed. Retroperitoneal lymphocysts were revealed in 4.3% of the cases. Of all stage I disease lymphocysts had developed in 2.8% of cases and in stage II 7.2%. Correlations between lymph node metastatic damage and development of lymphocysts were not found. The peak incidence (6.2-6.4%) of lymphocysts appeared to be in women younger than 30 and in elderly women (over 60 years). Unilateral lymphocysts developed more frequently (left-side in 38.9% in right-side in 33.3%) than bilateral ones (28.3%). In 32.5% of cases the size was less than 5 cm, in 42.3% of cases 6-10 cm and in 25.6% of cases more than 10 cm; 18% of the lymphocysts were asymtomatic and did not need any treatment. High temperature, pain, changes in blood occurring 4-5 days after surgery are indications of parametritis. Lymphocysts usually arise 11-12 days after surgery. Ultrasonography is a highly informative diagnosic method to detect this disease. In 23% of cases, the method of treatment was conservative therapy, 35.8% of patients had punctures, thus micro-drainage was performed and a cocktail injection into the cyst cavity was carried out. In 7.7% of cases lymphocyst resection and drainage was carried out. PMID- 11198040 TI - Clinical significance of numerical aberrations on chromosome 17 in uterine cervical and endometrial neoplasias. AB - In order to determine the clinical significance of numerical aberrations on chromosome 17 in uterine cervical and endometrial neoplasias, we investigated 140 cell specimens obtained from the uterine cervix and endometrium using the fluorescence in situ hybridization (FISH) method. These specimens consisted of ten normal cervical epithelium (NCE), 16 cervical intraepithelial neoplasias (CIN 1), 15 CIN 2, 35 CIN 3, 11 early invasive squamous cell carcinoma of the uterine cervix (early invasive SCC), 11 invasive SCC, 13 normal endometrium (NE), 17 endometrial hyperplasias (EH), and 12 endometrial ademocarcinomas (EA). After Papanicolaou staining on these specimens was decolorized, FISH was performed using chromosome 17 specific repetitive DNA probes. Signals of centromere of chromosome 17 in marked atypical cells were counted using a fluorescence microscope. There was a significant difference in the rate of cells with one signal on chromosome 17 between CIN 1 (7.1+/-0.7%) or 2 (7.0+/-0.5%) and CIN 3 (12.6+/-0.9%) (p<0.01), and also between CIN 3 and early invasive SCC (19.6+/ 1.0%) (p<0.01). The rate of cells with three signals was significantly increased when the uterine cervical lesions were progressive to CIN 3 (p<0.01). Cells with five or more signals occurred only in early invasive SCC and invasive SCC. There was a significant difference in the rate of cells with three signals between EH (4.8+/-0.6%) and EA (11.4+/-2.1%) (p<0.05). Cells with five or more signals occurred only in EA. Examination of the numerical aberrations on chromosome 17 in uterine cervical and endometrial neoplasias has been suggested to be useful as an additional method for the differential diagnosis of these lesions. PMID- 11198041 TI - Expression of bcl-2 and bax in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the uterine cervix. AB - Bcl-2 protein together with the pro-apoptotic protein bax, are thought to function by forming homo- and heterotypic dimers which control the progression to apoptosis. In this immunohistochemical study we investigated the expression of bcl-2 and bax apoptosis related proteins in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the uterine cervix. Twenty-four cervical intraepithelial neoplasias grade 1-2 (CIN I/II), 38 grade 3 (CIN III), and 53 invasive squamous cell carcinomas (ISCC) were investigated by immunohistochemical staining for bcl-2 and bax protein. Bcl-2 immunoreactivity was found in five of the 24 CIN I/II cases (20.8%), 18 of 38 CIN II cases (47.4%) and nine of 53 ISCC cases (17%). The positivity for CIN III was significantly higher than for CIN I/II or ISCC (p=0.0351 and p=0.0018, respectively). The percentage of bax immunopositivity was somewhat higher in CIN III than in CIN I/II but this slight difference was not statistically significant. Correlation of the immunostaining results with tumor grade revealed a significant difference for bcl-2 which was more frequently immunopositive in well-differentiated tumors than in poorly differentiated tumors. There was no significant relation between bax expression and tumor differentiation. Our results suggest that alterations of bcl-2 and bax expression may occur as a relatively early event in cervical tumorigenesis. PMID- 11198042 TI - Cervical sarcoma botryoides treated with conservative surgery and adjuvant chemotherapy: a case report. AB - A case of cervical sarcoma botryoides treated with conservative surgery and adjuvant monochemotherapy is presented. PMID- 11198043 TI - Complications following combined surgery (radical vulvectomy versus wide local excision) and radiotherapy for the treatment of carcinoma of the vulva: report of 73 patients. AB - Cancer of the vulva is uncommon, accounting for only 5% of all gynecologic malignancies, and usually occurs in women over 60 years of age. The historic treatment of choice for invasive squamous cell carcinoma of the vulva is radical vulvectomy with bilateral inguinal lymphadenectomy, which has produced excellent long-term survival. We retrospectively analyzed the complications of wide local excision plus postoperative radiotherapy compared with those of radical vulvectomy and bilateral lymphadenectomy plus pre-or postoperative radiotherapy in 73 patients with vulvar cancer. There were no significant differences among these treatments in terms of primary tumor control, 5-year disease-free survival, and overall survival. Based on these results, the best treatment alternative for advanced vulvar cancer is wide local excision plus radiotherapy, as this method retains the high survival of traditional therapy but has less morbidity. PMID- 11198044 TI - Sarcoma botryoides of the uterine cervix in a young woman: a case report. AB - Among the rhabdomyosarcomas, which represent an uncommon neoplasm of mesoderm origin comprising about 1% of all female genital malignancies, sarcoma botryoides (SB) is an embrional variant usually found in the vagina of infants and young children under 16 years of age. The onset of SB from the uterine cervix is very rare with a peak incidence in the second decade; only a few cases have been published in the international literature so far. The authors report a case of embryonal rhabdomyosarcoma of the uterine cervix which occurred in a young woman treated by radical surgery, followed by adjuvant chemotherapy and radiotherapy. PMID- 11198045 TI - Retroperitoneal epithelioid angiosarcoma presenting with lymph node metastases. Clinicopathological study of an extremely rare tumor. AB - A case of retroperitoneal angiosarcoma in a woman 39 years of age is reported. The tumor presented with inguinal (right) and iliac (left) lymph node metastases and a mass protruding under the left vaginal wall. The unusual morphology of the tumor demanded special immunohistochemical investigation (factor 8, CD 31, CD 34, pancytokeratin 20, LCA, S100, cytokeratin 7, CEA, MU1, HMB 45 and melan A) which confirmed the diagnosis of epithelioid angiosarcoma. The problems in the differential diagnosis and therapeutic approach are discussed. PMID- 11198046 TI - Immunohistochemical analysis of nm23-H1 expression in human cervical lesions. AB - Reduced expression of the metastasis suppressor gene nm23-H1 has been previously correlated with high tumor metastatic potential and fatal clinical outcome in several types of human carcinomas. The aim of the study was to identify the expression of nm23-H1 in a variety of premalignant and malignant cervical lesions. The study comprised 106 cervical biopsies obtained from 106 women ranging in age from 23 to 68 (median 42) years. Histologic slides stained with H&E were evaluated blindly by two pathologists and a consensus diagnosis was established for each case. In addition, immunohistochemical stain was employed and a monoclonal antibody against nm23-H1 (YLEM Rome, Italy) was used. Twenty five of the cervical biopsies showed changes of mild dysplasia (CIN I), whereas 28 demonstrated features of moderate dysplasia (CIN II) and 28 severe dysplasia (CIN III). In 25 cases infiltrating squamous cell carcinoma was identified. Expression of nm23-H1 was evident in 9/25 (36%) CIN I, 13/28 (46%) CIN II, 22/28 (78.5%) CIN III and 17/25 (68%) infiltrating carcinoma biopsies. Statistically significant differences were observed between CIN II and CIN III (p=0.003), and CIN II and infiltrating carcinoma (p=0.002) groups. Expression of the nm23-H1 gene in premalignant and malignant cervical lesions indicates that this gene may play a substantial role in carcinogenesis and tumor progression. PMID- 11198047 TI - Conseusus statements on prognostic factors in epithelial ovarian carcinoma. Report of the Consensus Meeting organized by the European Society of Gynaecological Oncology, ESGO. PMID- 11198048 TI - Evidence that long-lasting potentiation in limbic circuits mediating defensive behaviour in the right hemisphere underlies pharmacological stressor (FG-7142) induced lasting increases in anxiety-like behaviour: role of benzodiazepine receptors. AB - The hypothesis that benzodiazepine receptors mediate initiation of lasting behavioural changes induced by FG-7142 was supported in this study. Behavioural changes normally induced by FG-7142 were blocked by prior administration of the competitive benzodiazepine receptor blocker, Flumazenil. When cats were subsequently given FG-7142 alone, the drug produced lasting behavioural changes in species characteristic defensive responses to rodent and cat vocal threat. FG 7142 also induced long-lasting potentiation (LLP) of evoked potentials in a number of efferent pathways from the amygdala in both hemispheres. Flumazenil given prior to FG-7142 blocked LLP in all but one of the amygdala efferent pathways, suggesting benzodiazepine receptor dependence of initiation of LLP. Three physiological changes were most closely correlated with behavioural changes. LLP in the right amygdalo-ventromedial hypothalamic (VMH) and amygdalo periacqueductal gray (PAG) pathways coincided closely with behavioural changes, as did a reduced threshold for the right amygdalo-VMH evoked potential. Administration of Flumazenil after FG-7142 returned defensive behaviour to pre FG 7142 baseline levels in a drug-dependent manner. At the same time LLP only in the right amygdalo-PAG pathway was reduced by Flumazenil. LLP in other pathways and amygdalo-VMH threshold were unaltered by Flumazenil. Moreover, covariance analyses indicated that increased defensiveness depended solely on LLP in the right amygdalo-PAG. These findings support the view that maintenance of lasting increases in defensive behaviour depend upon LLP of excitatory neural transmission between amygdala and lateral column of the PAG in the right hemisphere. Moreover, FG-7142 may be a useful model of the effects of traumatic stressors on limbic system function in anxiety, especially in view of the recent data in humans implicating right hemispheric function in persisting negative affective states in post-traumatic stress disorder. PMID- 11198049 TI - Evidence that long-lasting potentiation of amygdala efferents in the right hemisphere underlies pharmacological stressor (FG-7142) induced lasting increases in anxiety-like behaviour: role of GABA tone in initiation of brain and behavioural changes. AB - The hypothesis that long-lasting potentiation (LLP) in amygdala efferents to the periacqueductal gray (PAG) of the right hemisphere mediates initiation of lasting increases in defensive response to rats induced by FG-7142 was supported in this study. GABA transmission was potentiated with Vigabatrin (gamma vinyl GABA, GVG), a suicide inhibitor of GABA transaminase. It was predicted that increasing GABA transmission would interfere with LLP and behavioural changes. The hypothesis was confirmed, for the most part. GVG given 1 day prior to FG-7142 prevented increased defensive response to rats as well as LLP in right amygdala efferent transmission to the PAG. It did not prevent LLP in the left amygdalo-PAG pathway, although LLP duration was shortened. Nor did it prevent LLP in the right amygdalo ventromedial hypothalamic (VMH) pathway, and LLP in this pathway was associated with a slightly increased response to vocal threat, but not to rats. GVG given without FG-7142 had no behavioural effects, although it did potentiate transmission in the left amygdalo-PAG pathway. The effects of increasing GABA transmission are consistent with the hypothesis that FG-7142 changes behaviour by inducing a failure of GABA transmission, which in turn facilitates NMDA transmission and NMDA dependent limbic LLP. Finally, the hypothesis that altering GABA tone would change the efficacy of Flumazenil from a neutral antagonist to an inverse agonist was tested on limbic transmission. The hypothesis was confirmed in the left amygdalo-VMH pathway, but no other. It was concluded that mechanisms other than a change in GABA tone account for the drug-dependent reversal of LLP in the right amygdalo-PAG by Flumazenil. The findings of the present study suggest that response to FG-7142 may be a useful model of the effects of traumatic stressors on limbic system function in anxiety. PMID- 11198050 TI - Manipulation of operant responding for an ethanol-paired conditioned stimulus in the rat by pharmacological alteration of the serotonergic system. AB - It is becoming increasingly clear that environmental stimuli play a critical role in the maintenance of drug taking behaviour. This has led to investigations into the neural mechanisms by which environmental stimuli can come to control behaviour using paradigms such as conditioned reinforcement. The majority of this work has involved the use of food-paired conditioned stimulus rodent paradigms. Relatively few studies have attempted to investigate the neuropharmacology of behaviour maintained by presentation of a stimulus paired with ethanol drinking. Several lines of research support an important role for brain serotonin (5-HT) neurotransmitter systems in the control of alcohol drinking behaviour. The aim of the present study was, initially, to establish a procedure in which rats respond for an ethanol-paired conditioned stimulus, and second, to study the effects of a range of serotonergic compounds previously shown to be effective in reducing oral ethanol self-administration, on responding for this conditioned stimulus. Results showed that the 5-HT releaser d-fenfluramine, the selective serotonin reuptake inhibitor fluoxetine, the 5-HT1A receptor agonist 8-hydroxy-2[di-n propylamino]tetralin, the partial 5-HT1A receptor agonist buspirone, and the 5 HT1B/5-HT2C receptor agonist 1-(3-trifluoromethylphenyl)piperazine, but not the 5 HT2A/5-HT2C receptor agonist 1-(2,5-dimethoxy-4-iodophenylaminopropane)-2, selectively reduced responding on a lever leading to presentation of an ethanol paired conditioned stimulus. In addition the non-specific D1/D2 dopamine receptor antagonist haloperidol was active in this paradigm. Results are consistent with involvement of the dopaminergic and 5-HT systems, in particular activation of 5 HT1A and 5-HT1B receptor subtypes, in mediation of the conditioned or secondary reinforcing properties of ethanol. PMID- 11198051 TI - Different effect of desipramine on locomotor activity in quinpirole-treated rats after repeated restraint and chronic mild stress. AB - We have studied the effect of chronic treatment with the tricyclic antidepressant drug desipramine on locomotor activity in rats challenged with the administration of the D2-like dopamine agonist quinpirole, after prolonged exposure to two different stress regimens, repeated restraint stress and chronic mild stress (different stressors randomly presented). These stress schedules have been previously reported to influence in opposite ways the sensitivity to the locomotor response mediated by the stimulation of mesolimbic dopamine receptors. In particular, repeated restraint has been reported to induce an increased response to the locomotor effect of amphetamine, while chronic mild stress has been reported to induce a decreased locomotor response to quinpirole. In the present study, repeated restraint stress failed to influence the locomotor activity after challenge with quinpirole, while chronic mild stress reduced this response. Chronic treatment with desipramine failed to influence this response in the control group, but exerted opposite effects in the two stressed groups. In particular, chronic desipramine reduced locomotor activity in quinpirole-treated rats in the restraint stress group, and increased it in the chronic mild stress group, thus preventing the subsensitivity induced by this stress regimen. The present results, taken together with results from earlier studies, are consistent with the hypothesis that the effect of antidepressants on the sensitivity of the mesolimbic dopamine receptors mediating the locomotor behavioural response tends to be opposite with respect to that exerted by stress, regardless of its direction. However, since we failed to show an increased locomotor activity after quinpirole challenge in the repeated restraint group, this hypothesis remains to be demonstrated. The two stress schedules reduced body weight gain in a similar way, therefore their different effects do not seem to be due to a difference in stress severity. Thus, the observation that both stress schedules reduced body weight gain in a similar way, but only chronic mild stress reduced the sensitivity to the locomotor response to quinpirole, shows that this effect is not an artefact of body weight decrease. PMID- 11198052 TI - Clozapine pharmacokinetics and pharmacodynamics studied with Cyp1A2-null mice. AB - The aim of this study was to use the CYP1A2-null mouse to investigate the in-vivo contribution of CYP1A2 to clozapine pharmacokinetics and pharmacodynamics. An intraperitoneal injection of 10 mg/kg clozapine was administered to four male CYP1A2 -/- mice and four male wild-type mice. Clozapine, desmethylclozapine, and clozapine N-oxide concentrations in sequential tail blood samples were measured by HPLC with UV detection. Behavioural parameters were recorded at each time point. The area under the curve (AUC) of clozapine was 2.6 times greater, the clearance of clozapine was 2.6 times slower, and the half-life was 1.2 times longer in the CYP1A2 -/- mice (p = 0.0143) as compared to the wild-type mice. Sixty-one percent of the clozapine clearance in wild-type mice was calculated to be mediated by CYP1A2. The AUC of desmethylclozapine was 1.6 times lower in the CYP1A2 -/- mice compared to the wild-type mice (p = 0.0286), while there was a trend for the AUC of clozapine N-oxide to be greater in the CYP1A2 -/- mice (p = 0.0571). The CYP1A2 -/- mice were significantly more drowsy and showed more motor impairment (p = 0.0145) and myoclonus than the wild-type mice. Our results indicate that, in vivo, CYP1A2 is the major determinant of clozapine clearance, contributes significantly to the demethylation of clozapine, and has a negligible contribution to the N-oxidation. Our data also indicate that CYP1A2 poor metabolizers might be more susceptible than extensive metabolizers to dose related adverse effects of clozapine, such as sedation, myoclonus and seizures. PMID- 11198053 TI - Acute effects of LI 160 (extract of Hypericum perforatum, St John's wort) and two of its constituents on neuroendocrine responses in the rat. AB - Extracts of Hypericum perforatum (St John's wort), such as LI 160, which are effective antidepressants have several active constituents. Their mode of action in depression, however, is unclear. In the present investigation, we assessed the effect of equivalent doses of LI 160 and two of its components, hypericin and hyperforin on serotonin (5-HT) and dopamine (DA)-mediated neuroendocrine responses in the rat. LI 160, hypericin and hyperforin significantly and equivalently increased plasma corticosterone. This effect was blocked by ketanserin but not WAY-100635, suggesting mediation via 5-HT2 receptors. LI 160 also lowered plasma prolactin and prevented the increase in plasma prolactin following haloperidol administration. Hyperforin had a similar but somewhat less pronounced effect. We conclude that LI 160, hypericin and hyperforin all increase 5-HT-mediated corticosterone release while LI 160 enhances DA-mediated inhibition of prolactin release. Hyperforin may contribute to the facilitatory effect of LI 160 on DA function, but hypericin does not. PMID- 11198054 TI - D2 receptor occupancy under recommended and high doses of olanzapine: an iodine 123-iodobenzamide SPECT study. AB - The aim of this study was to compare the degree of striatal dopamine D2 receptor availability in patients treated with recommended (5-20 mg, mean dose 11.9 +/- 6.3 mg daily) and higher doses (25-40 mg, mean 32.1 +/- 5.6 mg daily) of the novel antipsychotic drug olanzapine by means of [123I] IBZM Single photon emission computed tomography (SPECT). The results were compared to those of a group of 10 untreated, healthy, age- and sex-matched controls. The degree of dopamine D2 receptor occupancy in the patient group was correlated with the presence of extrapyramidal symptoms (EPS). A total of 20 patients who met the DSM III R criteria for schizophrenia or schizoaffective disorder received a clinically effective antipsychotic monotherapy with olanzapine. The mean daily dose of olanzapine ranged from 0.05-0.6 mg/kg body weight. The dopamine D2 receptor binding was reduced in all patients treated with olanzapine. Specific IBZM binding expressed as the [STR-BKG]/BKG ratio ranged from 0.13-0.61 (healthy controls 0.95). The D2 receptor availability revealed an exponential dose response relationship (r = - 0.85, p < 0.001). The frequency of EPS induced by olanzapine was considerably lower. Only one patient, treated with 40 mg olanzapine, suffered from severe EPS symptoms and had to be given biperiden. There were no significant differences in the presence of EPS symptoms between patients with recommended doses and those with higher doses of olanzapine. PMID- 11198055 TI - Individual differences in mood reactions to d-amphetamine: a test of three personality factors. AB - Individual differences in self-reported mood following either 5 mg or 10 mg d amphetamine challenge were examined in order to test the modifying role of three factors of personality, viz., the Eysencks' psychoticism, Cloninger's novelty seeking, and Depue and Collins' extraversion. In a double-blind study, mood measures (energetic arousal, tense arousal, and hedonic tone) were taken immediately following a single-dose of d-amphetamine and then again after 90 min. The results showed significant psychoticism x d-amphetamine interactions for both drug doses: d-amphetamine increased energetic arousal and hedonic tone, and reduced tense arousal, only in low psychoticism individuals; in high psychoticism individuals, it led to lowered energetic arousal and hedonic tone, and increased tense arousal. Neither novelty seeking nor extraversion modified the effects of d amphetamine. These data suggest a link between psychoticism and dopaminergic functioning, although they do not rule out the involvement of other transmitter systems (e.g. noradrenergic). In common with other studies, such findings point to the important role that well-established factors of personality play in accounting for individual differences in reactions to psychoactive drugs. It is concluded that the routine inclusion of personality measures in future psychopharmacological studies may help to refine the characterization of drug effects. PMID- 11198056 TI - Sleep and daytime sleepiness the next day following single night-time dose of fluvoxamine, dothiepin and placebo in normal volunteers. AB - To explore the effects of sedating and non-sedating antidepressants, we conducted a placebo-controlled, double-blind cross-over study in 12 normal subjects of the effects of a single night-time dose of fluvoxamine 100 mg, dothiepin 100 mg or placebo on night-time sleep recorded at home, and sleepiness and performance the following day. Night-time sleep was altered significantly by both drugs, with main effects on rapid eye movement (REM) sleep and sleep continuity. Dothiepin increased total sleep time, REM latency and stage 2 sleep and decreased arousals, wake after sleep onset and stage 1, whereas fluvoxamine decreased total sleep time and REM time and increased wake after sleep onset. Sleep latencies in daytime naps were significantly shorter for dothiepin and longer for fluvoxamine, showing that subjects were more sleepy when taking dothiepin. Electroencephalograms (EEG) performed during performance tasks failed to distinguish significantly between drugs. There were no significant differences between groups on our measures of tracking performance or reaction time; however, these tasks were designed primarily to provide a standard setting in which to monitor continuous EEG, and were unsuitable to detect sleepiness effects themselves. Saccadic eye movement velocity, acceleration and deceleration showed small non-significant changes after both drugs. Mood self ratings showed no significant differences among the groups. Subjective measures of night-time sleep reflected the objective measures of sleep continuity, and the items for difficulty and speed of wakening in the morning were significantly higher (i.e. more difficulty and slower) in the dothiepin group. The home-recorded sleep findings after fluvoxamine in this study were very similar to sleep laboratory studies with other antidepressant drugs, thus providing more validation of the home recording method. PMID- 11198057 TI - Effects of pentagastrin and the cold pressor test on the acoustic startle response and pupillary function in man. AB - Pentagastrin, a cholecystokinin2 (CCK2) receptor agonist, evokes autonomic and subjective features of anxiety in healthy volunteers. The present experiments examined the effects of pentagastrin on two responses with known sensitivity to another anxiogenic procedure (threat of electric shock): the acoustic startle response and the pupillary light reflex. The effects of pentagastrin were compared with those of the cold pressor test, a procedure known to elicit sympathetic activation. Twelve healthy males (18-35 years) participated in two experiments each consisting of two sessions in which they received (1) pentagastrin (0.3 microg/kg, i.v.) and a control infusion (saline), and (2) cold pressor test (90 s hand immersion at 4 degrees C) and a control immersion (37 degrees C), using a balanced single-blind protocol. Electromyographic responses of the orbicularis oculi to 40 ms, 1 kHz, 115 dB tones ('startle responses') [Experiment 1], and miotic responses to 200 ms, 0.43 mW/cm2 light pulses [Experiment 2] were recorded before, during and after the infusions and hand immersions. Heart rate, blood pressure and subjective feelings were also recorded. The amplitude of the startle response was not significantly affected by pentagastrin, but was reduced during the cold pressor test. Resting pupil diameter increased during both pentagastrin infusion and the cold pressor test, but neither procedure altered the amplitude of the light reflex. Tachycardia, increased blood pressure and subjective anxiety were induced by both pentagastrin and the cold pressor test. The cardiovascular and mydriatic effects of pentagastrin and the cold pressor test are consistent with the known ability of these treatments to induce sympathetic activation. The anxiety induced by these treatments, unlike anxiety induced by threat of electric shock, was not accompanied by potentiation of the startle response or reduction of the miotic response. The results indicate that different anxiogenic procedures do not have equivalent effects on these reflexes. PMID- 11198058 TI - Selective cognitive processing of drug cues in heroin dependence. AB - Previous studies provide evidence for the selective processing of disorder related stimuli on anxiety, depression, and eating disorders. There exist some preliminary indications that selective processing of drug cues may be involved in drug craving and relapse that deserve further investigation. In order to investigate the role of processing bias in an abnormal motivational system, the attentional bias for drug related stimuli was studied in a heroin dependent population. Heroin dependent participants (n = 21) and control participants (n = 30) performed a supra- and subliminal heroin Stroop task and heroin craving was assessed. Heroin dependent participants showed a considerable attentional bias for supraliminally presented heroin cues. However, there was no evidence for a preattentive bias on the subliminal presented cues. Reaction time on heroin cues was significantly predicted by heroin craving-levels. Results indicate that selective processing may be related to motivational induced states in general. The finding are discussed in the context of selective information processing in general psychopathology and in motivational processes as addiction specifically. PMID- 11198059 TI - Residual effects of hypnotics on disengagement of spatial attention. AB - In an earlier study, we postulated that the residual effects of hypnotics could induce a spatial attention disengagement deficit independent of any decrease in alertness. To test this hypothesis, we compared the residual effects of zolpidem, zopiclone and flunitrazepam in two ocular saccade tests, gap and overlap. In the gap paradigm, the lateral target is illuminated 200 ms after the extinguishing of the central target. In the overlap paradigm, the central target stayed on when the lateral target was illuminated. Zopiclone increases latency in the overlap, but not in the gap test, which appears to be specific to a deficit of disengagement of spatial attention. Zopiclone impairs the saccadic precision in gap, but not in overlap, which may be interpreted as an impairment of visuospatial memory. The effects of zolpidem are limited to visuospatial impairment. The effects of flunitrazepam are massive and probably the results of a decrease in alertness. PMID- 11198060 TI - Adverse effects associated with the use of donepezil in general practice in England. AB - Donepezil is an acetylcholinesterase inhibitor indicated for the symptomatic treatment of mild to moderate Alzheimer's disease. It is reported to have a relatively favourable side-effect profile. We report here on a pharmacovigilance study carried out post-marketing in England. An observational cohort study using the technique of Prescription-Event Monitoring was carried out. Some 1762 patients (mean age 72.9 years; 42% male) were followed up for 6 months minimum. The commonest adverse events were nausea, diarrhoea, malaise, dizziness and insomnia. Aggression, agitation and abnormal dreams were uncommonly associated with the drug. There were no cardiac rhythm disturbances or liver disorders causally associated. The commonest adverse drug reactions are already reported in the product information. Given the relatively small size of this cohort, the signals of abnormal dreams and psychiatric disturbance as possible adverse drug reactions need further investigation in carefully planned studies. PMID- 11198061 TI - Refractory schizophrenia and atypical antipsychotics. AB - Treatment resistant or refractory schizophrenia is a difficult to define condition of largely unknown prevalence. For 10 years, clozapine has been the standard treatment in this condition and is recognized unequivocally as being effective. However, clozapine is sometimes poorly tolerated and has the potential for severe toxicity. Partly as a result of this, other atypicals have recently been evaluated as treatments for refractory schizophrenia. In order to evaluate the evidence base relating to the drug treatment of refractory schizophrenia, we developed a refractoriness rating based on previous work. Using this rating, we assessed all trials of atypicals in schizophrenia unresponsive to at least one drug. Overall, clozapine was consistently shown to be effective in refractory schizophrenia, even when stringently defined. Data relating to olanzapine and risperidone are equivocal at best, and there is some evidence to suggest that they are less effective than clozapine. There is essentially no cogent evidence to support the use of any other atypical in refractory schizophrenia. Clozapine remains the drug of choice in this condition. PMID- 11198062 TI - Dopaminergic sensitivity and prediction of antidepressant response. PMID- 11198063 TI - Serotonin, stress and corticoids. PMID- 11198064 TI - Methodological issues in community-based studies of gynecological morbidity. AB - This report describes the lessons learned from a series of community-based studies of gynecological morbidity among young married women in Karnataka State, India. Women's self-reports of symptoms of illness were found to be responsive to the context of the interview and the nature of questioning. In particular, women appeared much readier to report symptoms to lay interviewers after being invited to undergo a clinical examination in the near future than they were if no examination were offered. Little consistency was found in the results obtained from interviews, clinical examinations, and laboratory tests. Apparently, no alternative exists to the collection of biological specimens for laboratory analysis when estimates of disease prevalence are needed. Use of generic health related quality-of-life assessments is recommended for future surveys. Prospective studies will yield more valuable data on these topics than will cross sectional surveys. PMID- 11198065 TI - Can poor countries surmount high maternal mortality? AB - Does poverty bind developing countries to high levels of maternal death in childbirth? Or, as safe-motherhood advocates claim, do public health and social policy interventions have the potential to accelerate maternal mortality transitions? Globally, almost one in 200 live births leads to the death of the mother, making maternal mortality an issue of critical international import. This article presents an analysis of the determinants of national maternal mortality levels with a view to shedding light on these questions. A cross-national regression of 64 countries shows that wealth indicators explain only a portion of the variance in national maternal mortality levels. Other determinants, including women's educational levels and the proportion of deliveries attended by trained health personnel, are more clearly associated with national maternal mortality levels than are measures of wealth. The results offer grounds for optimism concerning the potential for global safe-motherhood efforts to induce maternal mortality transitions. PMID- 11198066 TI - The effect of gender preference on contraceptive use and fertility in rural Egypt. AB - Data are used from two surveys of currently married women aged 15-44 conducted in 1979-80 and 1990-91 to explore the changing impact of gender preference on modern contraceptive use and on fertility in rural Menoufia, Egypt. The significantly positive effects on contraceptive use of having one or more sons in 1979 remained constant in 1990. Families without living sons had higher odds of having a birth than did families with two or more sons during 1979-80, and these relative odds were even higher in 1990-91 among families with three or more living children. The implications of these findings for subsequent declines in aggregate fertility are discussed. PMID- 11198067 TI - Abortion trends in Japan, 1975-95. AB - In this study, recent trends in the incidence of induced abortion are analyzed in order to identify the target population and its requirements for family planning policy in Japan. Abortion statistics from 1975 to 1995 from the Ministry of Health and Welfare are reviewed. The abortion rate (the number of cases of induced abortion per 1,000 women per year) for women younger than 20 increased during the study period. The abortion ratio (number of cases per 1,000 live births) remained the highest among women aged 40-44. An increase in the abortion ratio was seen in the two youngest groups (younger than 20 and 20-24), especially among those who were born after 1955. The proportion of abortions experienced by women younger than 25 increased from 18 percent between 1976 and 1980 to 30 percent between 1991 and 1995, and a slight increase was also observed among women aged 40-44. The proportion of abortions performed after eight weeks of a pregnancy for the two youngest groups remained higher than that for older age groups during 1975-95. The analysis demonstrates that women younger than 25 should be the principal concern of family planning policy in Japan. Further investigations on unintended pregnancy are recommended. PMID- 11198068 TI - Women's reports of severe (near-miss) obstetric complications in Benin. AB - This study examines the validity of a survey instrument on near-miss obstetric complications. Three groups of women--with severe complications, with mild complications, and with a normal delivery--were identified retrospectively in three hospitals in South Benin and interviewed at home. The concept of "near miss" was used to identify women with severe episodes of morbidity. The questionnaire was able to detect, with some accuracy, eclamptic fits, abnormal bleeding in the third trimester for a recall period of at least three to four years, and all episodes of bleeding independent of timing within a period of two years. Questions concerning dystocia and infections of the genital tract generated disappointing results except when information on treatment was included. Overall, better results were achieved for antepartum and acute events. Severity made a positive difference only in the case of eclampsia, with an increase in sensitivity. The implications of the results for using women's recall of obstetric complications in surveys are discussed. PMID- 11198069 TI - Mobilizing demand for contraception in rural Gambia. AB - A community trial was conducted in rural Gambia in order to determine whether a community-based intervention designed to mobilize latent demand for contraception would increase use of modern contraceptives, even in the absence of improved availability of family planning services. Analysis of trial data indicates that the demand-mobilization intervention had a statistically significant positive effect on nonusers' adoption of modern contraception and that coterminous implementation of an intervention designed to improve access to services offered no additional benefit. The program component found to have the greatest impact was the "kabilo approach," in which village women provide basic health and family planning counseling to other women in their extended families. These results suggest that the principal barriers to increased contraceptive use in rural Gambia are psychosocial and that these barriers can be overcome through village based interventions designed to provide socially appropriate counseling to potential contraceptive users. PMID- 11198070 TI - Directional microphones--they work. PMID- 11198071 TI - Clinical application of the satisfaction with amplification in daily life scale in private practice I: statistical, content, and factorial validity. AB - Statistical, content, and factorial validity of the Satisfaction with Amplification in Daily Life (SADL) scale was assessed. SADL subscales closely correspond to four satisfaction domains. Subjective benefit is a key component of satisfaction, but other nonauditory factors contribute to wearer satisfaction, notably telephone use and appearance. Results confirm the SADLs psychometric properties and verify its use to validate hearing aid fitting satisfaction in private practice settings for a general patient population at 1-year postfitting. Interim SADL norms may be refined as more SADL data are obtained for different patient populations, hearing aid types, and fitting environments. PMID- 11198072 TI - Comparison of benefits provided by different hearing aid technologies. AB - The performance of 40 hearing-impaired adults with the GN ReSound digital BZ5 hearing instrument was compared with performance with linear hearing aids with input compression limiting (AGC-I) or two-channel analog wide dynamic range compression (WDRC) instruments. The BZ5 was evaluated with an omnidirectional microphone, dual-microphone directionality, and a noise reduction circuit in combination with dual-microphone directionality. Participants were experienced hearing aid users who were wearing linear AGC-I or analog WDRC instruments at the time of enrolment. Performance was assessed using the Connected Speech Test (CST) presented at several presentation levels and under various conditions of signal degradation and by the Profile of Hearing Aid Benefit (PHAB). Subjective ratings of speech understanding, listening comfort, and sound quality/naturalness were also obtained using 11-point interval scales. Small performance advantages were observed for WDRC over linear AGC-I, although WDRC did not have to be implemented digitally for these performance advantages to be realized. Substantial performance advantages for the dual microphones over the omnidirectional microphone were observed in the CST results in noise, but participants generally did not perceive these large advantages in everyday listening. The noise reduction circuit provided improved listening comfort but little change in speech understanding. PMID- 11198074 TI - Effect of interstimulus interval on subjective categorical loudness judgements. AB - The Independent Hearing Aid Fitting Forum uses the visual input/output locator algorithm and the Contour Test of Loudness Perception to achieve the goal of restoring normal loudness perception with amplification. This method presupposes that subjective categorical loudness judgments are valid and reliable when using the procedure outlined by the test developers. There is no indication in the instructions of the Contour Test of a specific duration for interstimulus interval (ISI). The effect of ISI on loudness perception is important to establish because of potential time-error effects. Time-error refers to the extent to which the judged magnitude of a second stimulus varies with the time interval by which it follows the first stimulus. Past research has indicated that judgments of a second stimulus are shifted in the direction of the intensity of the preceding stimulus and that this effect intensifies with shorter ISIs. The current experiment was designed to examine whether a change in ISI produced a change in the loudness rating of the subsequent stimulus for subjective categorical loudness judgment testing. A trend toward lower, median dB values for ratings 2 to 5 at 500 Hz in a group of subjects with normal hearing was noted when 1-sec intervals were used in comparison with longer ISIs. No trends for the effect of ISI were noted at 3000 Hz. The findings provide ISI recommendations for loudness judgment test administration. PMID- 11198073 TI - Predicting directional hearing aid benefit for individual listeners. AB - The fitting of directional microphone hearing aids is becoming increasingly more routine, and this fitting option has proven to be a successful method to improve speech intelligibility in many noisy listening environments. Data suggest, however, that some hearing-impaired listeners receive significantly more directional benefit than others. It is of interest, therefore, to determine if directional benefit is predictable from identifiable audiologic factors. In this report, we examined whether the slope of audiometric configuration, amount of high-frequency hearing loss, and/or the aided omnidirectional performance for a speech-in-noise intelligibility task could be used to predict the magnitude of directional hearing aid benefit. Overall results obtained from three separate investigations revealed no significant correlation between the slope of audiometric configuration or amount of high-frequency hearing loss and the benefit obtained from directional microphone hearing instruments. Although there was a significant, negative relationship between aided omnidirectional performance and the directional benefit obtained in one study, there was considerable variability among individual participants, and nearly all of the listeners with the best omnidirectional hearing aid performance still received significant additional benefit from directional amplification. These results suggest that audiologists should consider the use of directional amplification for patients regardless of audiogram slope, high-frequency hearing loss, or omnidirectional speech intelligibility score. PMID- 11198075 TI - Recipient of the 2001 Pioneer Award. Philip J. Dziuk, Ph.D. PMID- 11198076 TI - Use of embryo transfer and IVF to bypass effects of heat stress. AB - Although heat stress has multiple effects to lower pregnancy rate in lactating dairy cows, a major pathway is in its effects on the early cleavage stage embryo. Conceptually, and in practice, higher pregnancy rates can be obtained with transfer of late cleavage stage embryos. The literature is reviewed, and conclusion is made that application of these technologies may be in part, a solution to this long-standing problem. PMID- 11198077 TI - Feed and forage toxicants affecting embryo survival and fetal development. AB - Early embryonic and fetal development in mammals is sensitive to deficiencies and excesses of specific nutrients and toxicants. Operating directly and/or indirectly, these deficiencies and excesses can result in embryonic death or, in less severe circumstances, disruption of normal embryo and fetal growth. This paper explores the threats posed by feed and forage toxicants to the developing embryo and their impact on early programming of fetal development. Using significant examples, we consider the relevance of temporal sensitivities during early development in utero, and their implications for the morphology and functional competence of specific organs and tissues. PMID- 11198078 TI - Endocrine disrupting compounds: effect of octylphenol on reproduction over three generations. AB - With the growing concern that environmental chemicals might impair human and animal fertility, it is important to investigate the possible influence of these substances on sexual differentiation and genital development of mammals. Many of these substances are suspected to interfere with endocrine processes, and exposure during critical periods of prenatal development might affect reproductive performance over several generations. Alkylphenols and their metabolites are lipophilic substances exerting apparent estrogenic action in in vitro and in vivo testing systems. With the widespread industrial use of alkylphenols, these are disseminated in the environment with sewage sludge, and domestic animals and humans are likely to be exposed via the food chain. Using the pig as an in vivo model, we studied the effect of intrauterine exposure to tertiary octylphenol (OP) on essential reproductive parameters over 3 generations. Sows were treated daily from D 23 to 85 of pregnancy with either 0, 10 or 1000 micrograms OP/kg body weight. Treatment with OP extended pregnancy length and induced basal cell proliferation in the cervical epithelium of the parental generation. In F1 offspring of sows treated with the low dosage of OP, onset of puberty was accelerated. Furthermore, when F1 gilts and F1 boars originating from sows treated with high dosages of OP were bred, the litter size was reduced. The results of the present study are compared with previous reports on estrogenicity of OP, and the usefulness of in vivo animal or embryo models for the evaluation of possible consequences of human exposure to endocrine disrupting compounds is discussed. Furthermore, possible consequences of exposure to endocrine disrupting compounds for the embryo transfer industry are addressed. PMID- 11198079 TI - Recent progress in livestock genomics and potential impact on breeding programs. AB - Most of the major livestock breeding organizations in the world are actively involved in using the emerging tools for genome analysis to obtain a better understanding of the molecular architecture of their favourite production traits. This is bound to generate a considerable amount of novel biological information that will provide a competitive advantage to those that have access to it. At present, the preferred avenue to exploit this information is via marker-assisted selection (MAS), and several breeding organisations are starting to implement MAS in breeding programs. However, it seems unlikely that the exploitation of genomics information will be limited to MAS in the future. Even though it is difficult to anticipate the ultimate impact of genomics on animal production, it would be very surprising if it were not to revolutionize this industry as it is already revolutionizing the biomedical and plant breeding industries. PMID- 11198080 TI - Influence of in vitro systems on embryo survival and fetal development in cattle. AB - In vitro systems are commonly used for the production of bovine embryos. Comparisons between in vivo and in vitro produced embryos illustrate that the morphology of preimplantation-stage embryos differ significantly, the survival of embryos and fetuses is decreased, the size distributions of the populations of conceptuses and fetuses are altered throughout gestation, and placental development is significantly changed. Taken together these findings indicate that exposure to some in vitro environments during the first 7 days of life can profoundly influence fetal and placental development in cattle. An understanding of how in vitro oocyte maturation, in vitro fertilization, and embryo culture systems influence both fetal and placental development should result in systems that consistently produce normal embryos, fetuses, and calves. PMID- 11198081 TI - Genetic regulation of embryo death and senescence. AB - The survival of the preimplantation mammalian embryo depends not only on providing the proper conditions for normal development but also on acquiring the mechanisms by which embryos cope with adversity. The ability of the early conceptus to resist stress as development proceeds may be regulated by diverse factors such as the attainment of a cell death program and protective mechanisms involving stress-induced genes and/or cell cycle modulators. This paper reviews the recent research on the genetic regulation of early embryo cell death and senescence focussing on the bovine species where possible. The different modes of cell death will be explained, clarifying the confusing cell death terminology, by advocating the recommendations set forth by the Cell Death Nomenclature Committee to extend to the embryology research field. Specific pro-death and anti-death genes will be discussed with reference to their expression patterns during early mammalian embryogenesis. PMID- 11198082 TI - Genes regulating embryonic and fetal survival. AB - Embryonic mortality in both farm animals and humans occurs most frequently during the first few weeks after conception. It can be attributed to abnormalities in the earliest developmental processes during embryogenesis that include implantation, maternal recognition of pregnancy, and formation of the placenta and cardiovascular system. The molecular mechanisms that are essential for all of these early processes are being elucidated at a rapid pace using transgenic and gene knockout approaches in mice. Two important general conclusions have emerged from this work. First, placental defects can occur by a number of different molecular mechanisms and can result from defects in the development or function of its trophoblast, mesenchymal or vascular components. Second, placental and cardiovascular functions are intimately linked. Cells of the placenta, for example, produce hormones that have profound effects on maternal and fetal cardiac and vascular function. In addition, development of the two is linked mechanistically through the use of some genes that are essential for development of both. Understanding the molecular basis of these processes should help to address the major limits to the success of embryo transfer, IVF and embryo cloning practices in livestock species. PMID- 11198083 TI - Responsiveness of early embryos to environmental insults: potential protective roles of HSP70 and glutathione. AB - Early embryos are not as passive as previously thought. In the bovine, embryos as early as the 2-cell stage can respond to environmental insults at both the cellular and molecular level by altering expression of specific genes and synthesis of proteins. Moreover, sex related differences exist in how early embryos respond to otherwise hostile environments. As aggressive as early embryos may be to tolerate environment insults, the majority will fail to continue in development. Reduced developmental potential of embryos exposed to elevated temperatures is likely due to direct effects on the early embryo. However, as embryos proceed in development they acquire the ability to better withstand environmental insults. Developmental acquisition of tolerance to environmental stress may be contingent upon acquisition of protective biochemical mechanisms or simply due to increased cell numbers. Correlative evidence has suggested a potential role of heat shock protein 70 and glutathione for protection of embryos in face of elevated temperature. Of these two possibilities, HSP70 appears least likely to play a significant role in developmental acquisition of thermotolerance. Bovine embryos as early as the 2-cell stage, are able to mount a heat shock response; a developmental stage that is most sensitive to elevated temperatures. A more likely candidate for conferring increased resistance of early embryos to elevated temperature is glutathione. PMID- 11198084 TI - Mechanisms for managing cellular and homeostatic stress in vitro. AB - The ability to maintain embryo development in culture depends upon the ability of the embryo to maintain cellular homeostasis. Disruptions in the ability to regulate cellular homeostasis such as pH, calcium levels and osmotic pressure result in perturbed development and a reduced ability to establish and maintain a pregnancy following transfer. Therefore, it is important that in vitro conditions are designed to minimize stress on the embryo and maximize the ability of the embryo to maintain cellular homeostasis. While embryos do exhibit a degree of plasticity and can adapt to their environment, this requires expenditures of extra energy which negatively impacts viability. Therefore, reducing stress by taking into account the physiology of the embryo is essential for the maintenance of developmental competence in vitro. PMID- 11198085 TI - Progress on methods of gene detection in preimplantation embryos. AB - The advent of the polymerase chain reaction (PCR) and the development of fluorescence in situ hybridization (FISH) have had a tremendous impact on preimplantation genetic diagnosis (PGD). While PCR is a powerful tool in detecting genetic diseases or molecular markers affecting quantitative trait loci, the main use of FISH is screening for chromosomal aberrations. This presentation reviews the recent progress in preimplantation genetic diagnosis with an emphasis on bovine embryos. In particular the importance of biopsy size and strategies to avoid PCR contamination are discussed. Alternative DNA amplification and detection methods as well as methods to meet the challenge of multiple locus detection for marker assisted selection are presented. PMID- 11198086 TI - Sex related embryo development. AB - Although sexual dimorphic development in the mammalian embryo prior to differentiation of the gonad has been documented, there are many seemingly conflicting observations and gaps in our understanding of this process. Conditions that influence the process include gamete interaction, that might give one sex and advantage in the fertilization process and in rates of blastomere cleavage that would allow one sex to accumulate cells at a faster rate. In this scenario, males could accumulate more cells within a defined window of development. Another key difference between males and females is the number of copies of genes located on the sex chromosomes. Transcripts from the Y-chromosome are thought to function as transcription factors, which could accelerate development. Conversely, the X-chromosome contains genes that code for rate limiting steps in pathways key to embryo metabolism and stress reduction. It can be envisioned that prior to X-chromosome inactivation in females, elevated levels of transcripts for such genes may enable greater protection from environmental stress and regulate growth. As we gain a better understanding of how males and female develop we will be able to exert greater control over the manipulation of the sex ratio for the offspring of domestic animals. PMID- 11198087 TI - Cloning to reproduce desired genotypes. AB - Cloned sheep, cattle, goats, pigs and mice have now been produced using somatic cells for nuclear transplantation. Animal cloning is still very inefficient with on average less than 10% of the cloned embryos transferred resulting in a live offspring. However successful cloning of a variety of different species and by a number of different laboratory groups has generated tremendous interest in reproducing desired genotypes. Some of these specific genotypes represent animal cell lines that have been genetically modified. In other cases there is a significant demand for cloning animals characterized by their inherent genetic value, for example prize livestock, household pets and rare or endangered species. A number of different variables may influence the ability to reproduce a specific genotype by cloning. These include species, source of recipient ova, cell type of nuclei donor, treatment of donor cells prior to nuclear transfer, and the techniques employed for nuclear transfer. At present, there is no solid evidence that suggests cloning will be limited to only a few specific animals, and in fact, most data collected to date suggests cloning will be applicable to a wide variety of different animals. The ability to reproduce any desired genotype by cloning will ultimately depend on the amount of time and resources invested in research. PMID- 11198088 TI - Genetic manipulation of sex differentiation and phenotype in domestic animals. AB - In mammals, a gene based sex determination system ensures that approximately 50% of offspring will be of the male sex and 50% will be of the female sex. In domestic animal production systems, this ratio is not always ideal. Recent advances in our understanding of the molecular biology of sex determination and differentiation, as well as in the control of gene expression and the direct modification of animal genomes, allows us to consider methods for the direct genetic manipulation of sexual phenotype. PMID- 11198089 TI - Is stress really all that important? AB - There is growing concern in many parts of the world that fertility of dairy cattle is reducing as milk yields increase. Stress could be one important cause. As an example, fertility is lower after caesarian operations. Delayed uterine involution after dystocia is associated with abnormal ovarian cyclicity and prolonged intervals to the next pregnancy. There is a greater reduction in fertility as the clinical conditions of lameness, milk fever or mastitis worsen. Changes in social groupings greatly increase the number of inseminations required per pregnancy. Transport reduces the number of CL after superovulation, and can interfere with pregnancy rates after estrous synchronization. Embryos collected from heat-stressed donors are less viable and have delayed trophoblast function. Human-animal interactions influence stress-responses in cattle--the behavior of stockman and embryo transfer personnel could affect success. Putting aside financial aspects, exposure of an animal to avoidable stress compromises welfare, whether application of biotechnology is involved or not. The fact that stressors can be deleterious to such an important function as reproduction, emphasizes that stress is very important and should be minimized whenever possible. PMID- 11198090 TI - Effects of hormonal treatments on reproductive performance and embryo production. AB - Developments in the use of drugs to improve reproduction and embryo production have focused on estrus and ovulation synchronization protocols and embryonic survival. Protocols for synchronization of ovulation eliminate the need for detection of estrus and allow timed insemination of all cows enrolled. Various estrogenic, progestational, GnRH and PGF2 alpha-like drugs are used to synchronize follicle development, CL regression and induction of ovulation. Strategies are discussed to optimize such programs to maximize herd pregnancy rates. Use of bovine Somatotrophin (bST) in combination with the Ovsynch protocol resulted in increased pregnancy rates, indicating possible effects on oocyte and embryonic development. Treatment of embryo donor cows with bST reduced the proportion of unfertilized oocytes and increased the number of transferable embryos. Furthermore, bST increased pregnancy rate when given to the recipient. Sub-luteal plasma progesterone concentrations after insemination have been associated with lower pregnancy rates. Injection of hCG on day 5 post insemination resulted in induction of an accessory CL, increased plasma progesterone concentrations and increased conception rates. Strategies involving the use of sustained GnRH agonists to enhance CL development and alter follicular development are considered for future programs to enhance pregnancy rates. PMID- 11198091 TI - Adverse impact of heat stress on embryo production: causes and strategies for mitigation. AB - The production of embryos by superovulation is often reduced in periods of heat stress. The associated reduction in the number of transferable embryos is due to reduced superovulatory response, lower fertilization rate, and reduced embryo quality. There are also reports that success of in vitro fertilization procedures is reduced during warm periods of the year. Heat stress can compromise the reproductive events required for embryo production by decreasing expression of estrus behavior, altering follicular development, compromising oocyte competence, and inhibiting embryonic development. While preventing effects of heat stress can be difficult, several strategies exist to improve embryo production during heat stress. Among these strategies are changing animal housing to reduce the magnitude of heat stress, utilization of cows with increased resistance to heat stress (i.e., cows with lower milk yield or from thermally-adapted breeds), and manipulation of physiological and cellular function to overcome deleterious consequences of heat stress. Effects of heat stress on estrus behavior can be mitigated by use of estrus detection aids or utilization of ovulation synchronization treatments to allow timed embryo transfer. There is some evidence that embryonic survival can be improved by antioxidant administration and that pharmacological treatments can be developed that reduce the degree of hyperthermia experienced by cows exposed to heat stress. PMID- 11198092 TI - Exercise program effects on one woman with multiple sclerosis, Crohn's disease, fibromyalgia syndrome, and clinical depression. PMID- 11198093 TI - The challenge of eliminating health disparities in North Carolina. PMID- 11198094 TI - 2000 annual report of the state health director. PMID- 11198095 TI - Addressing health professions shortage areas in eastern North Carolina. PMID- 11198096 TI - Learning the thunder. PMID- 11198097 TI - Climbing up the pyramid. My experience as a surgical resident at Duke, 1936-1942. PMID- 11198098 TI - Punctuality--the politeness of kings. PMID- 11198099 TI - An ultimate board exam. PMID- 11198100 TI - Improving office-based preventive care for diabetes. The beneficial results of a patient questionnaire and a flow chart. PMID- 11198101 TI - Functional anatomy of execution, mental simulation, observation, and verb generation of actions: a meta-analysis. AB - There is a large body of psychological and neuroimaging experiments that have interpreted their findings in favor of a functional equivalence between action generation, action simulation, action verbalization, and perception of action. On the basis of these data, the concept of shared motor representations has been proposed. Indeed several authors have argued that our capacity to understand other people's behavior and to attribute intention or beliefs to others is rooted in a neural, most likely distributed, execution/observation mechanism. Recent neuroimaging studies have explored the neural network engaged during motor execution, simulation, verbalization, and observation. The focus of this metaanalysis is to evaluate in specific detail to what extent the activated foci elicited by these studies overlap. PMID- 11198102 TI - A data compression method for image time series. AB - Image time series for functional studies frequently vary relatively little from one time point to the next. We describe here a method of lossless file compression that calculates the change in signal intensity as a char (one byte), as opposed to a short or long integer (usually two or four bytes), thus resulting in a compressed file size just over half the size of the original (a 2:1 compression ratio). The calculations and format are exceedingly simple; the compression time is comparable to the time required for a file copy, and is thus transparent to most users. The approach works equally well on any integer-based scanning modality, such as PET, CT, or DSA. Our purpose in this communication is to advocate it as a potential standard, to promote free interchange of scan data. PMID- 11198103 TI - A new approach to measure single-event related brain activity using real-time fMRI: feasibility of sensory, motor, and higher cognitive tasks. AB - Real-time fMRI is a rapidly emerging methodology that enables monitoring changes in brain activity during an ongoing experiment. In this article we demonstrate the feasibility of performing single-event sensory, motor, and higher cognitive tasks in real-time on a clinical whole-body scanner. This approach requires sensitivity optimized fMRI methods: Using statistical parametric mapping we quantified the spatial extent of BOLD contrast signal changes as a function of voxel size and demonstrate that sacrificing spatial resolution and readout bandwidth improves the detection of signal changes in real time. Further increases in BOLD contrast sensitivity were obtained by using real-time multi echo EPI. Real-time image analysis was performed using our previously described Functional Imaging in REal time (FIRE) software package, which features real-time motion compensation, sliding window correlation analysis, and automatic reference vector optimization. This new fMRI methodology was validated using single-block design paradigms of standard visual, motor, and auditory tasks. Further, we demonstrate the sensitivity of this method for online detection of higher cognitive functions during a language task using single-block design paradigms. Finally, we used single-event fMRI to characterize the variability of the hemodynamic impulse response in primary and supplementary motor cortex in consecutive trials using single movements. Real-time fMRI can improve reliability of clinical and research studies and offers new opportunities for studying higher cognitive functions. PMID- 11198105 TI - Winning the fight against perinatal AIDS transmission. PMID- 11198104 TI - Functional networks in motor sequence learning: abnormal topographies in Parkinson's disease. AB - We examined the neural circuitry underlying the explicit learning of motor sequences in normal subjects and patients with early stage Parkinson's disease (PD) using 15O-water (H2 15O) positron emission tomography (PET) and network analysis. All subjects were scanned while learning motor sequences in a task emphasizing explicit learning, and during a kinematically controlled motor execution reference task. Because different brain networks are thought to subserve target acquisition and retrieval during motor sequence learning, we used separate behavioral indices to quantify these aspects of learning during the PET experiments. In the normal cohort, network analysis of the PET data revealed a significant covariance pattern associated with acquisition performance. This topography was characterized by activations in the left dorsolateral prefrontal cortex (PFdl), rostral supplementary motor area (preSMA), anterior cingulate cortex, and in the left caudate/putamen. A second independent covariance pattern was associated with retrieval performance. This topography was characterized by bilateral activations in the premotor cortex (PMC), and in the right precuneus and posterior parietal cortex. The normal learning-related topographies failed to predict acquisition performance in PD patients and predicted retrieval performance less accurately in the controls. A separate network analysis was performed to identify discrete learning-related topographies in the PD cohort. In PD patients, acquisition performance was associated with a covariance pattern characterized by activations in the left PFdl, ventral prefrontal, and rostral premotor regions, but not in the striatum. Retrieval performance in PD patients was associated with a covariance pattern characterized by activations in the right PFdl, and bilaterally in the PMC, posterior parietal cortex, and precuneus. These results suggest that in early stage PD sequence learning networks are associated with additional cortical activation compensating for abnormalities in basal ganglia function. PMID- 11198106 TI - Parental notification legislation would be harmful. PMID- 11198107 TI - Arlene D. Bardeguez, MD award-winning physician. PMID- 11198108 TI - Senate passes health care reform package. PMID- 11198109 TI - Medical errors? A review of selected law cases. PMID- 11198110 TI - Cancer in people with AIDS in New Jersey. AB - A total of 2,460 persons with AIDS (PWA) and cancer were identified--2,159 men and 301 women--among 22,382 men and 7,931 women reported with AIDS from 1979-1995 in New Jersey. Of these, 50% were diagnosed with Kaposi's sarcoma (KS), 33% with non-Hodgkin's lymphoma (NHL), and the remainder with other cancers, including lung and bronchus, oral, cervical, Hodgkin's disease, and digestive other than anal. The proportions of PWA who also had cancer, specifically KS and NHL, varied significantly by gender, race, and mode of HIV transmission. These findings are discussed in terms of risk factors in addition to immunosuppression that may account for the higher rates of cancer among PWA than the general population. Cancer prevention and detection measures likely will become more important as PWA survive longer. PMID- 11198112 TI - Acquiring new equipment. The leasing decision. PMID- 11198111 TI - Medical examinations and appeals for NJ public service workers. AB - The state of New Jersey has more than 200,000 employees in merit system jobs, who are covered by the Department of Personnel's formal hiring mechanism, including a medical examination and appeals process in which physicians play an important role. The State Medical Examiners Panel provides an innovative and practical approach to supply the Merit System Board with independent and objective findings and medical recommendations regarding the appeals. This article summarizes this process and discusses the structure, functions, and outcomes of the medical examiners Panel. PMID- 11198113 TI - Aetna US healthcare FAQs. Continued. PMID- 11198114 TI - [Mechanisms of cellular defense in cadidiasis]. AB - The data obtained in this research on experimental lung candidiasis in mice suggest that a specific part of cellular resistance (thymus) evidently fails to play the leading role in initiating the infectious process. The major function of hindering candidiasis development belongs to neutrophilic leucocytes whose phagocytosis is eliminating the causal agents from the organism. PMID- 11198115 TI - [Differential diagnosis of oxyphilic (Hurthle cell) adenomas and carcinomas of the thyroid]. AB - Successful application of a double immunostaining of oxyphilic tumors with a specific antimitochondrial antibody and proliferative marker Ki-67 was made for the first time. Comparative study of proliferative activity did not show a statistically significant difference between Hurthle-cell adenomas and carcinomas. However, oxyphilic carcinomas had a statistically significant positive correlation between proliferative index and aggressive course of tumor, tendency to recurrence, high metastatic activity, tumor size, presence of necrosis and capsule penetration. PMID- 11198116 TI - [Histological and immunohistochemical characteristics of diffuse large cell B cell lymphomas]. AB - In the REAL classification, diffuse large B-cell non-Hodgkin's lymphomas are grouped together. We investigated histological variants and immunohistochemical profile of diffuse large B-cell lymphomas in 53 patients. Accuracy of the diagnosis was 73.6% without immunohistochemistry. The usefulness of immunophenotyping in making the correct diagnosis depended on a specific histological variant of diffuse large B-cell lymphoma. Variants with polymorphic and anaplastic morphology or massive reactive component have been diagnosed by routine histological methods with poor validity. PMID- 11198117 TI - [Structural changes in the brain in HIV infection complicated by drug addiction]. AB - Comparative analysis of brain alterations in drug addicts who were HIV seropositive and died of sepsis and HIV-seronegative addicts showed similarity of these changes which manifested with ganglion cell rarefaction and losses, changed neuron content of main structural-functional types; massive satellitosis and neuronophagia, massive glycosis and leucodystrophy. These changes were diffuse in seropositive patients and rather focal in seronegative patients. The authors, on the basis of these findings, suggest a wider spread of HIV infection in drug addicts; they express doubts in the secondary nature of HIV-encephalopathy and believe that drug addiction should be considered as factor promoting HIV infection development. PMID- 11198118 TI - [Liver fatty degeneration and chronic hepatitis HCV]. AB - Fatty degeneration in HCV-hepatitis is, according to the authors' data, an active process determining progression of liver fibrosis. This allow to formulate new approaches to treatment of chronic HCV-hepatitis. PMID- 11198119 TI - [Candidiasis of mucous membranes]. AB - The author presents a new concept of complex relationship between the organism and Candida. According to this concept there is transformation of Candida carriage into invasive candidiasis of the mucous membranes. The idea is formulated on mixed-mycocenosis as association of fungal, bacterial, protozoic and viral biota. For the first time the notion of intermediate preinvasive form of candidiasis is given and clinical, morphological criteria of differential diagnosis between candida carriage, preinvasive and invasive candidiasis of mucous membranes are presented. PMID- 11198120 TI - [Clinico-morphological and molecular-biological characteristics of idiopathic fibrous alveolitis and lung sarcoidosis]. AB - Lung biopsies of 16 patients with classic idiopathic fibrosing alveolitis (IFA) and 6 patients with sarcoidosis were studied immunohistochemically. It was found that adenomatous hyperplasia (AH) and fibrosing in IFA are potentiated by high expression of thrombocytic growth factor (TGF) and insulin-like growth factor type 1 (IGF-1). Tumor necrosis factor alpha (TNFa) in IFA is actively produced at early stages of the disease. TNFa is drastically reduced in IFA with atypical AH. High level of TNFa produced by alveolar macrophage, pneumocytes type 2 and by other cells is observed in the lungs in sarcoidosis. The level of transforming growth factor (B1-TGF) is rather low in sarcoidosis this being combined with weak interstitial fibrosis (3.75 against 5.06 in IFA). Sarcoidosis granuloma contains proliferating epithelioid cells (as judged by Ki-67), produces a high amount of FTN (4.66), moderate amount of cell fibronectin (2.7), fibroblast growth factor, beta-TGF and IGF-system (1.7; 1.1; 0.8, respectively). Thus, IFA and sarcoidosis are distinguished not only morphologically but by the cytokine profile as well. This implies different approaches to their diagnosis and treatment. PMID- 11198121 TI - [Morphology of lymphoid tissue from airways in bronchiectasis]. AB - Morphological and morphometrical study is performed on serial and stepped sections of the lungs surgically removed from patients with bronchoectatic disease. As compared to healthy persons, hyperplasia of all structural components with formation of lymphoid and lymphoepithelial follicles was detected. The degree of lymphoid tissue hyperplasia in bronchoectatic disease is determined by inflammation activity and does not depend on the age. The number of interepithelial lymphocytes is significantly increased as well as that of peribronchial and peribronchiolar lymphoid accumulations, and the degree of diffuse infiltration. However, the number of periglandular and periductal lymphoid accumulations and lymphoid follicles is significantly reduced. Bronchoectatic disease with high active inflammation as compared to low activity is characterized by more pronounced hyperplasia with formation of lymphoid and lymphoepithelial follicles with clear centers. PMID- 11198122 TI - [Dynamic morphologic follow-up of diabetic microangiopathy]. AB - Skin thigh biopsies were regularly taken in 186 patients with insulin-dependent and non-insulin-dependent diabetes. Progression of diabetic microangiopathy was found in spite of hypoglycemic treatment. Development of lesions of microvessels was somewhat inhibited only by angioprotectors (ticlid, dyamicron, dipiridamol). PMID- 11198123 TI - [Pathogenetic and morphological characteristics of acute inflammation of the central nervous system]. AB - Virus, bacteria, mycoplasma, protozoa can be the causes of acute neuroinfections. The agents can penetrate into the brain by blood, nerve, lymphatic vessels, from the sinuses directly. Peculiarities of manifestations of acute neuroinfections depend on the agent tropism to receptors of nervous cell and specificity of brain immunoreactivity. The brain injuries can be induced by microorganism action or through immunopathologic processes. Dynamics of morphological changes in acute neuroinfections of different etiology are summarized. Histological, cytological, bacteriological, serological, immunofluorescent, histochemical methods are evaluated. Acute neuroinfection pathogenesis has many unresolved problems. PMID- 11198124 TI - [The role of infection in the development of immune inflammation and pathogenesis of atherosclerosis]. AB - Pathogenesis of atherosclerosis from the point of view of immune inflammation in the vascular wall is discussed in this review. Potential role of adenoviruses and chlamydia in the development of immune inflammation and mechanisms and transport of infectious agents into the vascular wall and their influence on the cell kinetics are reviewed. PMID- 11198125 TI - Behavioural pharmacology and its contribution to the molecular basis of memory consolidation. AB - Recent findings have significantly advanced our understanding the mechanisms of memory formation. Most of these advances stemmed from behavioural pharmacology research involving, particularly, the localized infusion of drugs with specific molecular actions into specific brain regions. This approach has revealed brain structures involved in different memory types and the main neurotransmitter systems and sequence of metabolic cascades that participate in memory consolidation. Biochemical studies and, in several cases, studies of genetically manipulated animals, in which receptors or enzymes affected by the various drugs were absent or overexpressed, have complemented the pharmacological research. Although most studies have concentrated on the involvement of the hippocampus, many have also investigated the entorhinal cortex, other regions of the cortex, and the amygdala. Behavioural pharmacology has been of crucial importance in establishing the major neurohumoral and hormonal systems involved in the modulation of memory formation. These systems act on specific steps of memory formation in the hippocampus and in the entorhinal, parietal, and cingulate cortex. A specialized system mediated by the basolateral amygdaloid nucleus, and involving several neuromodulatory systems, is activated by emotional arousal and serves to regulate memory formation in other brain regions. The core mechanisms involved in the formation of explicit (declarative) memory are in many respects similar to those of long-term potentiation (LTP), particularly in the hippocampus. However, there are also important differences between memory formation and LTP. Memory formation involves numerous modulatory influences, the co-participation of various brain regions other than the hippocampus, and some properties that are specific to memory and absent in LTP (i.e. flexibility of response). We discuss the implications of these similarities and differences for understanding the neural bases of memory. PMID- 11198126 TI - Differential effects of 5-HT agonists and antagonists on the repeated acquisition and performance of response sequences in monkeys. AB - As a means of characterizing the role of 5-HT1A and 5-HT2A receptors in learning, 5-hydroxytryptamine (5-HT) agonists and antagonists with selective affinities for each receptor subtype (i.e. 8-hydroxy-dipropylaminotetralin (8-OH-DPAT), (-)-4 (dipropylamino)-1,3,4,5-tetrahydrobenz-(c,d,)indole-6-carboxamide (LY228729), (+/ )-1-(4-iodo-2,5-dimeth-oxyphenyl)-2-aminopropane hydrochloride (DOI), 4-iodo-N-[2 [4-(methoxyphenyl)-1-piperazinyl] ethyl]-N-2-pyridinyl-benzamide hydrochloride (p-MPPI), N-[2- [4- (2-methoxyphenyl)-1-piperazinyl] ethyl] -N-2-pyridinyl cyclohexanecarboxamide maleate (WAY-100635), 1-(2-methoxyphenyl)-4-[4-(2 phthalimido)butyllpiperazine hydrobromide (NAN-190) and ritanserin) were administered to monkeys responding under a multiple schedule of repeated acquisition and performance. In addition, a selective 5-HT1A receptor agonist (8 OH-DPAT) was administered in combination with a 5-HT2A receptor antagonist (ritanserin) to examine any potential interactions between the two 5-HT receptor subtypes. When administered alone, 8-OH-DPAT (0.1-3.2mg/kg), LY228729 (0.32-3.2 mg/kg) and DOI (0.018-3.2 mg/kg) dose-dependently decreased overall response rate in both schedule components, and generally increased the percentage of errors in the acquisition components at doses lower than those that increased the percentage of errors in the performance components. At the doses of each drug tested (i.e. 0.1 or 0.32 mg/kg), both p-MPPI and WAY-100635 antagonized the disruptive effects of 8-OH-DPAT, by shifting the dose-effect curves for overall response rate and the percentage of errors to the right. In contrast, ritanserin (0.32 or 1mg/kg) had little or no effect on the disruptions produced by 8-OH DPAT, but it effectively antagonized the rate-decreasing and error-increasing effects produced by the 5-HT2A agonist DOI. Administration of the 5-HT1A antagonists WAY-100635 and NAN-190 alone produced dose-dependent rate-decreasing effects, but the effects on accuracy of responding in the acquisition components differed from those of the 5-HT1A agonists (8-OH-DPAT and LY228729), in that they did not produce an increase in the percentage of errors. Together, these results suggest that 5-HT is capable of disrupting learning in monkeys through actions at both the 5-HT1A and 5-HT2A receptors, and that 5-HT2A receptor antagonism does not unilaterally modify the effects produced by 5-HTA1A receptor activation. PMID- 11198127 TI - A comparison of fixed and variable doses of cocaine in producing and augmenting tolerance to its effects on schedule-controlled behavior. AB - Twelve pigeons were trained to peck a key under a fixed-ratio 20-response schedule of food presentation. Acute effects of cocaine (03-10.0 mg/kg), determined by administering the drug once per week, revealed dose-dependent decreases in frequency of key pecking. The pigeons were then divided into six pairs, matched with respect to acute dose-response curves. One of each pair received one of five different doses before each daily session (variable-dosing condition) and the other received a fixed dose equal to the arithmetic average of the doses experienced by its pair mate (fixed-dosing condition). Following 50 days of exposure, subjects in the variable-dosing condition were then switched to the fixed-dosing condition. Dose-response functions were then determined in both groups by substituting doses for the fixed daily dose, once per week. Rate decreasing effects were attenuated similarly in both groups of subjects, both at the end of the variable-dosing regimen and during subsequent fixed dosing. Next, an attempt was made to increase the degree of tolerance. Specifically, pigeons in the variable-dosing condition were exposed repeatedly to a range of doses in which the largest dose was 1/8 to 1/4 log unit larger than in the original variable-dosing phase. Pigeons in the fixed-dosing group were exposed daily to the largest dose that did not eliminate key pecking by the end of the initial repeated-dosing regimen. Dose effects were determined after at least 35 days of exposure. If the dose-response function had shifted to the right, the largest dose for the variable-dosing subjects was increased by 1/8 to 1/4 log unit and the smallest dose in the sequence was eliminated, and another period of variable dosing commenced. For the fixed-dosing subjects, if the curve had shifted to the right, the fixed dose was increased by 1/8 to 1/4 log unit and the process repeated. Only very modest shifts of the dose-response function to the right were observed, and in several cases curves shifted left after exposure to larger doses. Overall the results suggest that a variable-dosing regimen holds promise as a technique for investigating the development of tolerance to the effects of cocaine, and that the magnitude of tolerance cannot be increased to any great degree by increasing the dose or doses repeatedly experienced. Additionally, it appears that experience with relatively large doses of cocaine may limit the degree to which tolerance can be developed, or decrease the magnitude of tolerance previously observed. PMID- 11198128 TI - Effects of MAO inhibitors upon MPTP mice chronically treated with suprathreshold doses of L-dopa. AB - Groups of mice were administered either saline or 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) (2 X 40 mg / kg, s.c., separated by a 24-hour interval) 4-6 weeks prior to behavioural testing. At testing, all the MPTP-injected mice were repeatedly administered L-dopa (20 mg / kg, s.c., five times each week, Monday-Friday), by applying a procedure that induced a severe reduction of motor activity parameters from Day 1 to Day 25. Control (uninjected mice) received only saline and were retained only for neurochemical analysis. In each of three experiments, following the reduction of the activity-stimulating effects of L dopa by repeated administration, a restorative effect of different monoamine oxidase (MAO) inhibitors was tested by co-administration of the test compounds (irreversible MAO-B inhibitor, reversible MAO-A inhibitors, or irreversible MAO-A / mixed MAO inhibitors) with L-dopa (20 mg / kg). In each case the MAO inhibitor was injected 60 min prior to L-dopa. L-Deprenyl (3 or 10 mg / kg, s.c.), in combination with L-dopa, reinstated locomotion and total activity, but not rearing, dose-dependently, in L-dopa-tolerant mice. The reversible MAO-A inhibitors, amiflamine and alpha-ethyltryptamine, in combination with L-dopa, reinstated locomotion and total activity, leaving rearing unaffected; Ro 41-1049 (3 mg / kg, s.c.) restored all three parameters of activity; locomotor activity was restored by all three doses (1, 3, and 10 mg / kg, s.c.). On the other hand, neither the irreversible MAO-A inhibitor, clorgyline, nor the mixed MAO inhibitor, phenelzine, produced any directly effective restorative increments. Neurochemical analysis confirmed the severe striatal dopamine depletion of MPTP treated mice. These results demonstrate a synergistic and restorative action of combining certain MAO inhibitors, namely the reversible MAO-A inhibitors, with the suprathreshold dose of L-dopa in MPTP-treated, L-dopa-tolerant mice. PMID- 11198129 TI - Place aversion induced by blockade of mu or activation of kappa opioid receptors in the dorsal periaqueductal gray matter. AB - Neural circuits in the dorsal periaqueductal grey matter (DPAG) play an important role in the integration of defensive behaviour. As considerable numbers of mu and kappa opioid receptors have been found in this region, we studied the effects of morphine, [3H]-[H-D-Phe-Cys-Tyr- D-Trp-Orn-Thr-Pen-Thr-NH2] (CTOP), a selective peptide antagonist for mu opioid receptors, U-50488H, a specific agonist for kappa opioid receptors, and nor-binaltorphimine (nor-BNI), a long-lasting selective antagonist for kappa opioid receptors, injected into the DPAG of rats submitted to the corral method, a conditioned place preference test. The behavioural testing apparatus was a circular open field consisting of four uniform quadrants that were equally preferred by the rats prior to drug treatments. For conditioning, rats received drug injections on three consecutive days and were placed into their assigned quadrant. Injection of 40 nmol of morphine into the DPAG produced place aversion effects, with reduced time spent in the drug-paired quadrant on the testing day. These place aversion effects were not inhibited by previous DPAG microinjection of CTOP (1 nmol) but were significantly reduced by prior systemic injections of nor-BNI (2 mg / kg). Microinjection of CTOP alone produced a clear decrease in the time spent in the treatment quadrant, whereas nor-BNI alone did not. Similarly, microinjection into the DPAG of the kappa agonist U-50488H (10 nmol) mimicked the effects of morphine, also producing place aversion for the drug-paired quadrant. These findings suggest that blockade of mu opioid receptors or activation of kappa opioid receptors in the DPAG may produce conditioned place aversion. PMID- 11198130 TI - Ethanol-induced conditioned place aversion in mice. AB - Previous studies have shown that ethanol produces conditioned place preference (CPP) in mice when injections are given immediately before exposure to the conditioned stimulus (CS). Paradoxically, however, injection of ethanol immediately after the CS produces conditioned place aversion (CPA). Four experiments were conducted to characterize the parametric boundaries of CPA produced by post-CS ethanol exposure. Experiment 1 showed that CPA is positively related to ethanol dose, with significant CPA at 2 and 4 g / kg, but not at 1 g / kg. Experiment 2 revealed an inverse relationship between CPA and trial duration, i.e. significant CPA occurred when the trial duration was 5, 15 or 30 min, but not when it was 60 or 90 min. Experiment 3 indicated that ethanol pre-exposure (eight daily injections) significantly reduced subsequent development of CPA. Finally, experiment 4 showed that repeated exposure to the CS alone (six 30 min exposures to each CS) after CS-ethanol pairings produced complete extinction of CPA. The same extinction procedure also completely eliminated CPP induced by pre CS injections of ethanol. Overall, these studies demonstrate that CPA induced by post-CS ethanol injection is influenced by many of the same variables that affect CPP produced by pre-CS ethanol injection in mice. However, these findings do not resolve the issue of whether the 'before-versus-after' effect in ethanol place conditioning is better explained by assuming ethanol produces only rewarding effects or by assuming that ethanol produces both rewarding and aversive effects. PMID- 11198131 TI - Influence of training history on ethanol discrimination in rats. AB - The compound stimulus hypothesis of ethanol discrimination predicts that a history of training to discriminate drugs that mimic individual elements of the ethanol stimulus should attenuate stimulus control by other stimulus elements (associative blocking). Rats were trained initially to discriminate either chlordiazepoxide (5 mg / kg s.c., n = 10) or dizocilpine (0.08 mg / kg i.p., n = 10) from vehicle in two-lever procedures with food reinforcers presented on a tandem variable-interval fixed ratio schedule. Control rats received 'sham training' (vehicle injections only, n = 9). All subjects were then trained to discriminate ethanol (1.5 g / kg intragastrically (i.g.)) until discrimination accuracy reached 95%. Chlordiazepoxide (1.25-10.0 mg / kg s.c.) produced more drug-appropriate responding in rats with a previous history of training to discriminate chlordiazepoxide than in either of the other two groups, but stimulus control by dizocilpine was not attenuated. Equivalent results were obtained in rats with a previous history of training to discriminate dizocilpine. Ethanol (0.375-3.0 g / kg i.g.) produced similar dose-related increases in drug appropriate responding in all three groups. Thus, previous discrimination training modified the characteristics of ethanol discrimination in a way that may be explained by persistence of the original discriminations. The lack of evidence for associative blocking contrasts with results of previous experiments on the discrimination of compound stimuli produced by administering drug mixtures. The findings provide limited support for the hypothesis that ethanol produces a compound stimulus that includes elements of positive modulation of gamma aminobutyric acid (GABA(A)) receptors and of N-methyl-D-aspartate (NMDA) antagonism. PMID- 11198132 TI - Nicotine enhances acquisition of a T-maze visual discrimination: assessment of individual differences. AB - In the present report, rats' performance was assessed in five tasks designed to measure behavioral response to different novel stimuli under different experimental situations. Daily nicotine treatment (0, 0.3 or 1.0 mg / kg) began after the conclusion of the behavioral tasks and continued throughout the experiment. Training of a T-maze visual discrimination task commenced after 11 days of nicotine pretreatment. As a group, rats treated with the higher dose of nicotine (1.0 mg / kg) made fewer errors to acquire the initial T-maze discrimination than saline-treated controls. Activity induced by an inescapable novel environment (i.e. first behavioral screen) was positively correlated with the number of errors to acquire the initial discrimination in the T-maze for the two nicotine-treated groups (0.3 and 1.0 mg / kg). To examine this positive correlation further, a median split analysis was conducted on the novelty-induced activity for each group. Nicotine, especially the high dose (1.0 mg / kg), enhanced performance in rats that were less active in the inescapable novel environment. Nicotine treatment did not affect the performance of rats that were more active in that environment. After the initial visual discrimination was acquired, the reverse discrimination was trained. Nicotine treatment did not affect performance; the number of errors to acquire the reversal for nicotine- and saline-treated rats did not differ. Overall a nicotine-induced improvement in performance is demonstrated which can be predicted by a rat's reactivity to environmental novelty. PMID- 11198133 TI - Moving out of the laboratory: does nicotine improve everyday attention? AB - The most robust demonstrations of the nicotine-related performance effects on human cognitive processes are seen in tasks that measure attention. If nicotine does have some potential for enhancing attention, the obvious question to ask is whether the effects demonstrated in the laboratory hold any significance for real life performance. This paper describes three studies that compare the effects in smokers of a single own brand cigarette on laboratory tests of attention and on everyday analogues of these laboratory tasks. In the laboratory measures of sustained attention and in the everyday analogue, performance advantages were registered in the smoking condition. These benefits were observed in smokers who abstained for a self-determined period of not less than 2 h. The studies were unable to replicate previous research reporting positive effects of smoking on a laboratory task of selective attention, the Stroop task. Small but significant improvements in performance were registered in the everyday analogues, which involved sustaining attention in a dual task situation, a telephone directory search task and a map search task. In addition, smokers showed a significant colour-naming decrement for smoking-related stimuli in the Stroop task. This attentional bias towards smoking-related words occurred independent of whether they had abstained or recently smoked an own brand cigarette. The effect is discussed in terms of the two-component model of processing bias for emotionally valenced stimuli. PMID- 11198134 TI - D-Cycloserine, a positive modulator of NMDA receptors, inhibits serotonergic function. AB - The administration of the N-methyl-D-aspartate (NMDA)-associated glycine recognition site agonist D-cycloserine (DCS) to rats inhibited the head shakes and the forepaw treading induced by the serotonin (5HT) precursor, L-5-hydroxy tryptophan [(-)5HTP], as well as the forepaw treading and motility elicited by the selective 5HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8 OH-DPAT). The head shakes typically induced by the 5HT2 receptor agonist, 1-(2,5 dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI), were unaffected by DCS pretreatment. The results are consistent with reduced serotonergic transmission produced by NMDA activation, as suggested by other authors. Due to the important role played in the pathogenesis of schizophrenia by glutamate deficiency/serotonin activation, the results support the view that positive modulators of NMDA receptors, activating glutamate receptors and reducing serotonergic tone, might be useful in the alleviation of psychotic symptoms. However, because of its partial agonist properties at the glycine recognition site, D-cycloserine shows some effects that might make it unsuitable for clinical use. PMID- 11198135 TI - Serotonin, noradrenaline and cognitive function: a preliminary investigation of the acute pharmacodynamic effects of a serotonin versus a serotonin and noradrenaline reuptake inhibitor. AB - Comparisons of the behavioural side-effect profiles of antidepressants that inhibit either serotonin or both serotonin and noradrenaline reuptake, may reveal differences in cognitive and psychomotor functions, which may be attributed to their relative pharmacological selectivity for potentiating monoamine neurotransmission in the central nervous system. The aim of the present study was to determine the acute pharmacodynamic effects of citalopram and venlafaxine, on cognitive and psychomotor performance. Nine healthy male volunteers received a single clinical dose of citalopram, venlafaxine or amitriptyline (positive control) in a double-blind placebo-controlled design. Cognitive and psychomotor tests and a subjective measure of sedation were examined before and 1, 2 and 4 hours after drug administration. Citalopram improved psychomotor responses to sensory stimuli and sustained attention, with significant decreases in movement times of the choice reaction time test and an increase in critical flicker fusion threshold. Venlafaxine did not affect performances on any of the cognitive or psychomotor tests examined. Differences may be related to relative potencies of the compounds for monoamine reuptake inhibition. PMID- 11198136 TI - Neurotrophic keratitis. PMID- 11198137 TI - Treatable forms of retinitis pigmentosa associated with systemic neurological disorders. AB - In this chapter; we have described the role of nutritional supplements or selective dietary restriction (or both) on the maintenance and function of the retina and nervous system in some diseases. Oral vitamin A therapy has proven to be effective in the treatment of the common forms of retinitis pigmentosa. Bassen Kornzweig disease can be treated with vitamin A and vitamin E and, in some cases, with vitamin K. Vitamin E therapy for Friedreich-like ataxia associated with retinitis pigmentosa has been shown to be effective in the short term. Classic Refsum's disease responds to a low phytol-low phytanic acid diet. Undoubtedly, future research will bring more insight into the biochemical pathways responsible for other diseases and, it is hoped, aid in developing treatments for additional retinal degenerations associated with systemic neurological disease. PMID- 11198138 TI - Apoptosis, neuroprotection, and retinal ganglion cell death: an overview. PMID- 11198139 TI - Causes of enlarged corneal nerves. PMID- 11198140 TI - Retinal manifestations of morning glory disc syndrome. PMID- 11198141 TI - Nonglaucomatous cupping of the optic disc. AB - Optic disc cupping is a consequence of myriad disorders. The anatomy and vasculature of the disc provide great insight into why, how, and when ODC occurs in various conditions. Approaches to distinguish glaucomatous from nonglaucomatous causes of ODC should rely on patient history, visual fields assessment, and funduscopic findings, as described. Cupping can be seen with neurological processes, including benign tumors, that are treatable. The clinician must remain vigilant to detect uncommon but potentially threatening forms of nonglaucomatous optic disc cupping. PMID- 11198142 TI - Temporal arteritis. PMID- 11198143 TI - Cortical visual impairment in infants and children. PMID- 11198144 TI - Magnetic resonance imaging of primary anterior visual pathway tumors. PMID- 11198145 TI - Ocular findings in neurofibromatosis type 1. PMID- 11198146 TI - Uveitis with neurological manifestations. AB - Neurological symptoms are not rare in patients with various uveitic syndromes, and they can be used as a guide to diagnosis. Some of the findings are nonspecific, but others can be typical of certain pathological conditions (table). After combining the information obtained in the medical history with the physical examination, target-oriented laboratory and diagnostic tests may then be obtained to confirm a diagnosis. Neurological manifestations can be of great value throughout this process and clearly should be carefully evaluated in every patient with uveitis. PMID- 11198147 TI - Maculopathies that resemble optic neuropathies. AB - This chapter outlines some diseases in which diagnosis of retinal pathology can prove difficult and often mislead one to think of optic nerve disease. Clinicians should consider these entities when atypical features or unexplained visual loss occurs. A careful medical history, review of systems, and the appropriate use of ancillary studies (as outlined) can provide insights helpful in making the correct diagnosis. PMID- 11198148 TI - Leber's congenital amaurosis and RPE65. PMID- 11198149 TI - Neuroretinitis. AB - Despite the growing list of agents that can present as neuroretinitis, nearly one half remain idiopathic. However, many of the candidate etiologies are treatable conditions, and accurate diagnosis can result in visual rehabilitation. A complete workup in patients presenting with acute neuroretinitis should include a thorough history and general medical evaluation. Exposure history should be thoroughly explored, including recent travel, unpasteurized and uncooked foods, sexual experience, and animal contacts. A detailed physical examination should be performed to note hidden rashes and inoculation sites and should include routine measurements of blood pressure and heart rate. Laboratory tests should be tailored to the history and may include complete blood count; erythrocyte sedimentation rate; bacterial, fungal, and viral blood cultures; antinuclear antibody test; angiotensin-converting enzyme; anti-double-stranded DNA; and C3. Serological evaluation should look for syphilis, Lyme disease, histoplasmosis, brucellosis, chlamydia, HIV, toxoplasmosis, Epstein-Barr virus, viral hepatitis B and C, and tuberculin skin test. Neuroretinitis is a clinical entity in which there is inflammation of the retinal architecture and optic nerve. There are numerous entities that can cause a picture of neuroretinitis ranging from vascular to infectious to autoimmune. With regards to the infectious etiologies, it is interesting to note that many of these organisms are obligate intracellular pathogens. The microorganisms B. henselae, T. gondii, R. typhi, T. pallidum, Mycobacterium tuberculosis, Histoplasma capsulatum, and various viruses, such as HIV, mumps, and HSV, are known intracellular agents. Other major infectious agents, such as B. burgdorferi and Leptospirosis spp. are known to remain sequestered within the circulatory system. It is possible that in this way these agents are able to breach the delicate blood-brain barrier. The implication of such findings on the treatment and management of neuroretinitis remains to be explored. Interestingly, the vast majority of infected patients do not develop neuroretinitis or demonstrate CNS involvement. Detailed examination of this variability may provide further insight into the pathogenic properties of these infectious agents, host tissue susceptibility, and mechanisms of blood-retina barrier integrity. A detailed retinal examination can provide an unobstructed view of the CNS. Careful inspection of this delicate interface may reveal subtle findings critical for accurate and rapid diagnosis of underlying systemic pathology. The varied visual and neurological symptoms of neuroretinitis attest to the fact that this is a disease of both the retina and contiguous neuronal elements. Such involvement significantly elevates the risk to the patient and emphasizes the need for early detection and prompt treatment. PMID- 11198150 TI - Influence of chronic ethanol consumption on the muscarinic cholinergic control of rat pancreatic acinar cells. AB - There are a number of hypothetical explanations for the actions of ethanol on the exocrine pancreas; among them, the cholinergic hypothesis has received special attention. According to this hypothesis, chronic alcohol consumption induces alterations in the control of exocrine pancreatic function resulting in cholinergic hyperstimulation of pancreatic acinar cells and their muscarinic receptors. Our aim was to investigate the cholinergic control of pancreatic enzyme secretion and the number and affinity of muscarinic receptors in the pancreatic acinar cells of rats subjected to chronic ethanol ingestion. We also investigated whether a high-fibre diet modifies the actions of ethanol on these aspects of the exocrine pancreatic function. Four groups of rats received either a standard or a high fibre diet, and either water or 20% (v/v) ethanol. After 6 months of treatment, isolated pancreatic acini were used for the determination of carbachol-stimulated amylase secretion and for the analysis of muscarinic receptors, using 1-[N-methyl-3H]scopolamine as a radioligand. Neither chronic ethanol intake nor a high fibre diet caused any apparent alteration in pancreatic histology, neither did them modify plasmatic amylase levels. Chronic alcoholization resulted in a significant increase in the amylase released from pancreatic acini in response to carbachol stimulation, but it did not affect either the number or the affinity of pancreatic acinar muscarinic receptors. The actions of ethanol are not significantly modified by the simultaneous consumption of a high fibre diet. PMID- 11198151 TI - Self-design of fish diets by means of self-feeders: validation of procedures. AB - In this paper, we show the results from four different experiments in which sea bass, maintained under laboratory conditions, could choose between two or three different diets through self-feeders, which gradually increased the complexity and potential range of selection, to design their own diet in accordance with their requirements. At first, sea bass were allowed to select between two complete diets differing in the proportion of protein (52-58%): this showed their capacity to distinguish between two diets made of the same ingredients. Next, two incomplete diets, containing a fixed amount of protein (56%) and lacking either fat or carbohydrate, were made available. Three mixed diets made up of pairs of macronutrients (protein-carbohydrate, protein-fat or fat-carbohydrate) were tested in the next experiment and, finally, three diets containing only one macronutrient (protein fat or carbohydrate) were made available to fish. Taking into account selection made by the fish in the first three experiments, in which macronutrient selection was statistically different, protein was the main macronutrient chosen by fish (278.15 kJ/kgBW/day, on average), followed by fat and carbohydrate (162.85 and 64.56 kJ/kgBW/day, respectively). In conclusion, the results reveal the ability of sea bass to select an appropriate diet from experimental diets containing two or three macronutrients and suggest that the proposed methodology is a powerful tool for studying the differing nutritional needs of different species of fish. PMID- 11198152 TI - Effects of chronic insulin treatment on blood pressure in rats. AB - There is an evident epidemiological association between plasma insulin levels and blood pressure. The mechanism that relates insulin to blood pressure and the role of insulin in the pathogenesis of arterial hypertension have not been clearly defined. The present study was designed to examine the effects of chronic hyperinsulinism on blood pressure and to determine different related morphological variables. WistarKyoto rats were subcutaneously injected with insulin (25 UI/Kg of weight) daily during the eight weeks of the experiment. Data were collected on systolic and diastolic arterial pressures and heart rate by plethysmography and direct recording (in the last week), and on morphological variables. A statistically significant elevation of systolic arterial pressure was produced after the sixth week of hyperinsulinaemia. At the end of the treatment, the systolic arterial pressure was 173.7 +/- 26.1 in the hyperinsulinaemic rats versus 153.09 +/- 21.7 in the control group. The values obtained by direct recording and by plethysmography did not differ. These results indicate that chronic hyperinsulinism produces a significant elevation in systolic blood pressure levels in the rats studied. PMID- 11198153 TI - Effects of antioxidants on calcium signal induced by cholecystokinin in mouse pancreatic acinar cells. AB - Digital imaging fluorescence microscopy was used to study the effect of two antioxidants, N-acetyl-cysteine (NAC) and glutathione, on the cytosolic free calcium concentration ([Ca2+]i) induced by cholecystokinin-octapeptide (CCK-8) of mouse pancreatic acinar cells. When acinar cells were preincubated with either NAC or glutathione, subsequent stimulation with CCK-8 in the presence of each antioxidant had no significant effect on the typical pattern of [Ca2+]i transient evoked by the gastrointestinal hormone. However, application of NAC to acinar cells pretreated for 60 min with the same antioxidant, strongly blocked the oscillatory pattern initiated by CCK-8, inhibiting both amplitude and frequency of calcium oscillations. By contrast, glutathione had no effect on the oscillatory pattern evoked by CCK-8. The present results allow us to speculate that during [Ca2+]i oscillation there is a production of oxidants that facilitate oscillations by enhancing release of calcium from internal stores. PMID- 11198154 TI - Role of prostanoids and nitric oxide inhibition in rats with experimental hepatic fibrosis. AB - Nitric oxide (NO) and prostaglandins have been proposed as vasodilator substances involved in peripheral vasodilatation characteristic of the liver cirrhosis. A link between NO and prostanoids has been suggested. The present study investigated the effect of simultaneous blockade of both, NO synthase (NOS) and cyclooxigenase (COX) in sham-operated (SO), or rats with bile-duct ligation (BDL) in the development of liver fibrosis. Animals were distributed in two groups SO (n=15) or BDL (n=15). Treatments (5 days) started three weeks after surgical procedure. Both, SO and BDL animals were treated with indomethacin (INDO) (5 mg/kg/day) alone, with NG-nitro-L-arginine-methyl-ester (NAME) (4 mg/kg/day) alone or with INDO and NAME combination at the same doses. At the end of follow up body weight, packed cell volume, mean arterial blood pressure (MAP) and heart rate were measured. Liver tissue was processed for histological studies. In this study, BDL animals showed a decreased MAP. Treatment with L-NAME in BDL rats increased MAP. The chronic COX inhibition alone did not play an important role in the haemodynamic changes. The BDL produced a loss of hepatic structure, with ductular metaplasia that occupied the greater part of the hepatic parenchyma. Also, an important degree of fibrosis was observed. Both NO and PG synthesis inhibitors, alone or in combination, induced enhancing collagen fiber deposition in the hepatic parenchyma. These findings support the notion that the interaction between the NOS and COX pathways should be relevant in hepatic cirrhosis in which both NOS and COX are induced. PMID- 11198155 TI - Role of S-adenosylmethionine on the hepatobiliary homeostasis of glutathione during cyclosporine A treatment. AB - The effects of cyclosporine A (CyA) treatment on the hepatic content and biliary output of reduced (GSH) and oxidized (GSSG) glutathione and lipid peroxidation in the liver, and the ability of S-adenosylmethionine (SAMe) to antagonize the CyA induced alterations were studied in male Wistar rats. To evaluate the efficacy of SAMe, three CyA and SAMe protocols were used: cotreatment with SAMe plus CyA, pretreatment with SAMe before starting cotreatment, and post-treatment with SAMe after beginning treatment with CyA alone. CyA treatment for one and four weeks depleted liver GSH, decreased the GSH/GSSG ratio and significantly reduced GSH and GSSG biliary concentrations and secretion rates. Additionally, long-term treatment enhanced lipid peroxidation. By contrast, when the rats were treated with CyA plus SAMe using any of the administration protocols, SAMe was seen to be efficient in antagonizing the GSH hepatic depletion, the changes in hepatic GSH/GSSG ratio and the increase induced by CyA in lipid peroxidation. Furthermore, SAMe also abolished the effects of CyA on the biliary secretion rates of GSH and GSSG. The efficacy of SAMe was similar, regardless of the administration protocols used. In conclusion, our results clearly demonstrate that SAMe is good for preventing, antagonizing and reversing the CyA-induced alterations in the hepatobiliary homeostasis of glutathione. PMID- 11198156 TI - Influence of goat and cow milk on the digestive and metabolic utilization of calcium and iron. AB - The effects of goat and cow milk on the digestive and metabolic utilization of calcium and iron were studied in rats using a standard (non-milk) control diet. The digestive utilization of calcium is greater when the animals consume the goat milk-based diet rather than that based on cow milk or the standard diet. The digestive utilization of iron, however, is similar for the goat-milk diet and the standard diet, and in both cases superior to that based on cow milk. The calcium content in the femur, sternum and Longissimus dorsi muscle (L.D. muscle) provides an indication of what happens during the utilization of the mineral; more is deposited when the rats consume a milk-based diet, particularly one based on goat milk. The iron content in the reserve organs, namely the liver and the spleen, is greater with the standard diet and the goat milk diet than with that containing cow milk. There is an obviously beneficial effect of goat milk on the metabolism of calcium and iron, which minimizes any interaction between the two minerals. PMID- 11198157 TI - Patient-controlled analgesia with ketorolac in pediatric surgery. AB - Our aim was to quantify the analgesic efficiency of the patient-controlled analgesia technique (PCA), using ketorolac, in children aged 6-14 undergoing a surgical intervention. We carried out a double-blind test with two randomly selected groups: the PCA group comprising patients submitted to intravenous PCA, with "bolus on demand" and the Standard group, with conventional analgesia dispensed with ketorolac I.V. (0.5 mg/kg/6 hours). Evaluation of pain experienced was performed using the Hannallah behavioural scale and quantification of the summing of pain intensity. Analgesic efficiency was determined by the pain intensity difference (PID) score. Evaluation of pain experienced during hour 1 reveals a marked reduction with time for each group; no inter-group differences were found. At hour 6 there were neither intra-group nor inter-group differences. The accumulated pain score revealed a significant reduction in hour 6, with no differences between the two groups. Evaluation of the analgesic effect revealed no differences, either intra-group or intergroup, during the experimental period. The sum of the PIDs revealed significant differences in the standard group between the values for hours 1 and 6. Under the experimental conditions described, both techniques were equally effective for pain treatment, but the efficiency was higher for the PCA group. PMID- 11198158 TI - Effect of magnesium deficiency on enterocyte Ca, Fe, Cu, Zn, Mn and Se content. AB - In previous studies based on indirect procedures, we reported that Mg deficit increased the bioavailability of a number of elements such as calcium, zinc, iron, copper, manganese and decreased selenium absorption. The present study was designed to verify these findings by direct methods. We investigated the effect of dietary magnesium deficiency on enterocyte Ca, Fe, Zn, Cu, Mn and Se concentrations. Male Wistar rats were fed a Mg-deficient diet (129 mg Mg/kg food) for 70 days. Whole enterocytes from the upper jejunum were isolated and Ca, Fe, Zn, Cu, Mn and Se were determined. The results were compared with findings in a control group that was pair-fed with an identical diet except that it covered this species's nutritional requirements for Mg (480 mg Mg/kg food). The Mg deficient diet significantly increased enterocyte content of Ca, Fe, Zn, Cu and Mn; however, we found no significant changes in the Se content of these cells. These data support the results obtained by indirect methods. PMID- 11198159 TI - Physiological responses of pre-ruminant kid goats and lambs to different environmental temperatures. AB - The purpose of this study was to establish the metabolic behaviour of both preruminant kid goats and lambs, when they are kept at different environmental temperatures (12, 24 and 30 degrees C). The animals were fed ad libitum with a milk replacer for the first two months of life. Blood samples were taken from all the animals on days 30, 40, 50 and 60 post partum, to determine serum levels of glucose, insulin, free fatty acids, triiodothyronine (T3) and thyroxine (T4), both when fasting and 4 hours after starting feeding. The high sensitivity of both kinds of animal to the lowest of the environmental temperatures used, particularly for the first periods of life here considered, was established from the glucose/insulin and T3/T4 molar ratios and from the concentrations of free fatty acids. The results obtained by species were also evidence of metabolic behaviour typical of leanner animals in kids. PMID- 11198160 TI - Production of healthier goat milk. Use of a concentrate supplemented with a "protected" fat rich in PUFA. AB - In order to obtain healthier goat milk as far as its fat composition is concerned, milk production and composition trials were carried out with Granadina goats kept in semi-extensive breeding conditions. The animals were feeding indoors with a concentrate supplemented or not with 7% of fat conveniently protected against the action of rumen, which had 35% of polyunsaturated fatty acids (PUFA). The amount of milk produced was higher (p < 0.05) with consumption of the fat supplemented concentrate. At the same time, and although there was no difference in the milk concentration of fat and protein nitrogen (p > 0.05), the corresponding yields were higher for consumption of the fat supplemented concentrate. As for the composition of milk fat, the use of the supplemented concentrate resulted in fat with a higher (p < 0.05) concentration of PUFA and a lower (p < 0.05) concentration of stearic acid. At the same time, the concentration of medium chain triglycerides, which is the specific nutritional value particular to goats' milk, was the same whichever concentrate was consumed. PMID- 11198161 TI - Influence of heat treatment of casein in presence of reducing sugars on Zn solubility and Zn uptake by Caco-2 cells after in vitro digestion. AB - The effect of the heat treatment of casein in presence of reducing sugars on some aspects of Zn availability was investigated. Samples were prepared by mixing casein with glucose-fructose, and were used unprocessed (C) or heated (HC). Changes in Zn speciation after the in vitro digestion of the samples, both as part of a diet and in isolation, were studied. The uptake of soluble Zn from the digested samples was investigated in Caco-2 cells. After in vitro digestion, the percentage of precipitated Zn was significantly higher with the HC sample, both when digested alone and as a part of the diet. In assays with Caco-2 cells, a significant decrease in Zn uptake was observed when the uptake buffer contained the sample C digest, by comparison with the control buffer, without casein digest. When the digested heated mixture was added, Zn uptake by the cells was significantly lower than in either of the two other cases. It may be concluded that the heat treatment of casein in the presence of glucose-fructose has a negative effect on Zn availability because, after in vitro digestion, Zn insolubilization was enhanced and Zn uptake by the enterocyte was impaired, compared with the unheated mixture. In addition, the usefulness of Caco-2 cells in this kind of research has been shown. PMID- 11198162 TI - Effects of folic acid and amino acids supplementation on zinc intestinal absorption in the progeny of ethanol-treated rats. AB - This study was designed to examine the effects of supplementation with folic acid and amino acids in dams that consumed ethanol during gestation and lactation to see whether there is an improvement in the intestinal absorption of zinc in pup rats on the 21st day after birth. The rats were randomized into two groups: Ethanol-rats (EG) were administered ethanol during the pregnancy and lactation periods; the ethanol-folic acid group (EFG) received a folic acid and amino acid supplement concomitantly with ethanol administration during pregnancy and lactation. The dams were mated to obtain the first offspring. Two sets of experiments were performed on the offspring at 21 days after birth. In general, in the first set, jejunal zinc absorption in the offspring of EG and EFG groups showed a gradual increase along with increased perfusion time at all assayed concentrations. Jejunal zinc absorption expressed as nmol/intestinal surface was higher in the ethanol-folic acid group than in ethanol animals at all assayed concentrations except at 25 microM concentration. In the second set of experiments, distal ileum zinc absorption in the offspring of ethanolfolic acid dams showed a significant increase at all concentrations tested. These results indicate that supplementation of folic acid and amino acids to dams that consume ethanol during gestation and lactation increase serum and milk zinc levels, although the zinc ingestion is lower. In pups of the supplemented dams, the jejunal and ileal absorption of zinc increased; as a consequence, the serum zinc levels increased. The activity of alcohol dehydrogenase, a metaloenzyme dependent on zinc levels, also increased. PMID- 11198164 TI - Protein nutrition in fish: protein/energy ratio and alternative protein sources to fish meal. AB - Those interested in the design and manufacture of feeds for intensive fish farming face the basic concern of formulating mixtures for the best yield at the lowest costs. Of the macronutrients in the feed, protein has and continues to receive special consideration because fish present high and specific needs for this constituent. Traditionally, protein has been supplied primarily by fish meals. This paper presents a synthesis of the efforts made and the lines explored to achieve an effective reduction of the amount of fish meal in the feeds for fish, following two strategies: reduction of the protein in the feeds and the use of new raw materials to replace fish meal. PMID- 11198165 TI - The role of phytic acid in legumes: antinutrient or beneficial function? AB - This review describes the present state of knowledge about phytic acid (phytate), which is often present in legume seeds. The antinutritional effects of phytic acid primarily relate to the strong chelating associated with its six reactive phosphate groups. Its ability to complex with proteins and particularly with minerals has been a subject of investigation from chemical and nutritional viewpoints. The hydrolysis of phytate into inositol and phosphates or phosphoric acid occurs as a result of phytase or nonenzymatic cleavage. Enzymes capable of hydrolysing phytates are widely distributed in micro-organisms, plants and animals. Phytases act in a stepwise manner to catalyse the hydrolysis of phytic acid. To reduce or eliminate the chelating ability of phytate, dephosphorylation of hexa- and penta-phosphate forms is essential since a high degree of phosphorylation is necessary to bind minerals. There are several methods of decreasing the inhibitory effect of phytic acid on mineral absorption (cooking, germination, fermentation, soaking, autolysis). Nevertheless, inositol hexaphosphate is receiving increased attention owing to its role in cancer prevention and/or therapy and its hypocholesterolaemic effect. PMID- 11198163 TI - Effect of psychogenic stress on gastrointestinal function. AB - This review summarizes the studies published over the last twenty years on the effects of psychogenic stress on gastrointestinal function, using animal models. The effects of stress on gastric ulceration have received wide attention and the central and local mechanisms of mucosal damage have been, for the most part, clearly delineated. In comparison, relatively few studies have focused on the impact of stress on intestinal and colonic physiology, even though its influence on intestinal motility, mucosal permeability and inflammation has been established. More work is necessary in this field, especially considering the importance of irritable bowel syndrome in modern society. PMID- 11198166 TI - Adaptation of the exocrine pancreas to dietary fats. AB - This article reviews studies on the adaptation of the exocrine pancreas to dietary fat. We include all the latest information about the mechanisms that underlie the adaptation of the secretory mechanism of the exocrine pancreas to the amount and the type of dietary fat. We review the kinetics of pancreatic adaptation and the mediators of the adaptive response of the pancreas including cellular and molecular mechanisms (modulation of intracellular messengers and gene expression of the different enzymes and secretagogues involved in the adaptation process). At the same time we include our results in this field in dogs and humans. PMID- 11198167 TI - Potential of two epigeic and two anecic earthworm species in vermicomposting of water hyacinth. AB - The potential of two epigeic species (Eudrilus eugeniae Kinberg, and Perionyx excavatus Perrier) and two anecic species (Lampito mauritii Kinberg and Drawida willsi Michaelson) of earthworms was assessed in terms of efficiency and sustainability of vermicomposting water hyacinth (Eichhornia crassipes, Mart. Solm.). In different vermireactors, each run in duplicate with one of the four species of earthworms, and 75 g of 6:1 water hyacinth:cowdung as feed, vermicasts were produced with steadily increasing output in all the reactors. E. eugeniae was by far the most efficient producer of vermicasts, followed by the other epigeic P. excavatus. The two anecics came next, with D. willsi being the least effective which could generate only about half the quantity of vermicasts achieved in a corresponding time by E. eugeniae. In all the reactors, the earthworms grew well, increasing their weights by more than 250%. The maximum net gain of weight (average 30.7 g) was by E. eugeniae, followed by P. excavatus, L. mauritii and D. willsi. This trend, which followed the efficiency of vermicast production, was also shown in terms of reproductive ability as measured by the number of offspring produced by the four species. PMID- 11198168 TI - A re-appraisal of wood-fired combustion. AB - Targets for a considerable increase in electricity generation from renewables have been set in order to reduce greenhouse gas emissions and fossil fuel dependence. Extensive planting of willow, poplar and alder as energy crops has been planned for power generation plants which use wood as the fuel. The current trend is to use gasification or pyrolysis technology, but alternatively a case may be made for wood combustion, if wood becomes readily available. A range of wood-fired circulating fluidised bed combustion (CFBC) plants, using from 10 to 10,000 dry tonne equivalent (DTE)/day, was examined using the ECLIPSE process simulation package. Various factors, such as wood moisture content, harvest yield, afforestation level (AL) and discounted cash flow rate (DCF) were investigated to test their influence on the efficiency and the economics of the systems. Steam cycle conditions and wood moisture content were found to have the biggest effects on the system efficiencies; DCF and AL had the largest influences on the economics. Plants which could handle more than 500 dry tonnes/day could be economically viable; those using more than 1000 dry tonnes wood/day could be competitive with large-scale, conventional coal-fired plants, if sufficient wood were available. PMID- 11198169 TI - The role of HRT and low temperature on the acid-phase anaerobic digestion of municipal and industrial wastewaters. AB - Two identical 31 completely mixed reactors with solids recycling capabilities were used to investigate the effects of hydraulic retention time (HRT) and low temperatures on volatile fatty acid (VFA) production. One reactor was fed with a 1:1 ratio of diluted primary sludge and a starch-rich industrial wastewater, while the other was fed with diluted primary sludge alone. The VFA and soluble COD concentrations and specific production rates reached their highest values at 30 h HRT and at 25 degrees C. Further increase in HRT (at 25 degrees C) or decrease in temperature (at an HRT of 30 h) resulted in lower amounts of VFA and COD produced. All parameters related to VFA and COD production were significantly higher in the industrial-municipal reactor than in the municipal-only reactor. The VFA:COD ratios were very high, with values ranging from about 0.8 to 1.0 indicating that hydrolysis was the rate-limiting step. Degradation of proteins (measured by ammonia production) was inhibited by the starch-rich wastewater in the industrial-municipal reactor, while no evidence of inhibition was found in the municipal-only reactor. This study revealed that VFA production was feasible at low temperatures (down to 8 degrees C), particularly in the presence of the industrial waste. Ultimately, the amount VFA produced was adequate, in most cases, to support subsequent biological nutrient removal (BNR) processes. PMID- 11198170 TI - Soil biochemical activity and growth response of rice Oryza sativa in flyash amended soil. AB - Soil amended with different proportions of flyash, a solid waste generated from coal-fired thermal power plants, was evaluated as a soil conditioner and nutrient supplement during a field study on the growth of rice, Oryza sativa. Generally, pH and organic carbon (OC) content did not increase significantly (P > 0.05) in flyash amended soil, but significant increases (P < 0.05) in soil conductivity (32%), available phosphorus (48%) and organic matter (OM, 29%) were observed during harvest at the 20 t ha-1 flyash application rate. Amylase, invertase, dehydrogenase and protease activities, and CO2 evolution increased in flyash amended soil over the control. The pigment (chl-a, chl-b, and carotenoid) content in rice plants did not vary significantly (P > 0.05) between different flyash amendments. Total plants biomass and aboveground biomass increased (P < 0.05) significantly (17% and 25%, respectively) at the 20 t ha-1 flyash application. However, there was a retarded growth of underground biomass. Grain and straw yield increased by 21% and 18%, respectively, at 17.5 t ha-1 flyash amendment when compared to the control. Although, a significant increase (P < 0.05) in plant biomass and grain yield in flyash amended soil is encouraging from the point of waste disposal and management, elucidation of reasons for retarded growth in underground biomass will require additional research based on long-term studies. PMID- 11198171 TI - Enzyme assisted ensiling of alfalfa with enzymes by solid substrate fermentation. AB - A crude enzyme preparation, obtained by solid substrate fermentation (SSF) with a Gliocladium spp. and added at the 5% level to wilted or non-wilted alfalfa, improved the fermentation characteristics and stability of alfalfa silages as effectively as commercial preparations, Novo-Nordisk Celluclast 1.5 L and Viscozyme 120 L, applied at the 0.025% level. The effective dose of the crude enzyme costs about one-fourth of the cost of the commercial enzymes. PMID- 11198172 TI - The influence of aeration and hemicellulosic sugars on xylitol production by Candida tropicalis. AB - The influence of other hemicellulosic sugars (arabinose, galactose, mannose and glucose), oxygen limitation, and initial xylose concentration on the fermentation of xylose to xylitol was investigated using experimental design methodology. Oxygen limitation and initial xylose concentration had considerable influences on xylitol production by Canadida tropicalis ATCC 96745. Under semiaerobic conditions, the maximum xylitol yield was 0.62 g/g substrate, while under aerobic conditions, the maximum volumetric productivity was 0.90 g/l h. In the presence of glucose, xylose utilization was strongly repressed and sequential sugar utilization was observed. Ethanol produced from the glucose caused 50% reduction in xylitol yield when its concentration exceeded 30 g/l. When complex synthetic hemicellulosic sugars were fermented, glucose was initially consumed followed by a simultaneous uptake of the other sugars. The maximum xylitol yield (0.84 g/g) and volumetric productivity (0.49 g/l h) were obtained for substrates containing high arabinose and low glucose and mannose contents. PMID- 11198174 TI - Influence of substrate wood-chip particle size on shiitake (Lentinula edodes) yield. AB - Wood chips from four commercial hardwood sawmills were screened with 10 US standard sieves (4-0.21 mm) to assess particle size distributions. 96-98% of wood chips were < 4 mm while 95-99% of particles were > 0.21 mm. The majority (mean = 64.5%) of wood chips passed through US standard sieve size 14 (< 1.4 mm). Shiitake (Lentinula edodes) was grown in three crops to determine the effect of four particle size classes (1 = 2.8-4 mm; 2 = 1.7-2.8 mm; 3 = 0.85-1.7 mm; 4 = < 0.85 mm) on mushroom yield. Yields from substrates prepared with wood chips from class 4 (< 0.85 mm) were lower by 27.7%, 12.4% and 2% (mean = 14.9%) for Crops I, II, and III, respectively, when compared to controls. Profiling of wood chips may help growers optimize their production media and reduce production costs. PMID- 11198173 TI - Reclamation of a burned forest soil with municipal waste compost: macronutrient dynamic and improved vegetation cover recovery. AB - The reclamation of burned soils in Mediterranean environments is of paramount importance in order to increase the levels of soil protection and minimise erosion and soil loss. The changes produced in the content of total organic carbon (TOC), N (Kjeldahl) and available P, K, Ca and Mg by the addition of different doses of a municipal solid waste compost to a burned soil were evaluated during one year. The effect of organic amendment on the improvement in the vegetation cover after one year was also evaluated. The organic amendment, particularly at a high dose, increased the TOC and N-Kjeldahl content of the soil in a closely related way. The levels of available K in soil were also enhanced by the organic amendment. Although the effects on all three parameters tended to decrease with time, their values in the amended soils were higher than in the control soil, which clearly indicates the improvement in the chemical quality of the soil brought about by the organic amendment. The available P content did not seem to be influenced by organic treatment, while available Mg levels were higher than in the control during the first 4 months following organic amendment. The application of compost to the burned soil improved its fertility and favoured rapid vegetal recovery, thus minimising the risk of soil erosion. PMID- 11198175 TI - Effects of pig manure and wheat straw on growth of mung bean seedlings grown in aluminium toxicity soil. AB - Crop production in red soil areas may be limited by Al toxicity. A possible alternative to ameliorate Al toxicity is the application of such organic manure as crop straw and animal manure. A pot experiment was conducted to investigate the effects of organic materials on the alleviation of Al toxicity in acid red soil. Ground wheat straw, pig manure or CaCO3 were mixed with the soil and incubated, at 85% of water holding capacity and 25 degrees C, for 8 weeks. After the incubation, 14 seedlings of mung bean (Phaseolus aures Roxb) were allowed to grow for 12 days. Results showed that application of organic material or CaCO3 increased soil pH and decreased soil monomeric inorganic Al concentrations. Growth of mung bean seedling was improved sustantially by the application of organic material or CaCO3. Pig manure or wheat straw was more effective in ameliorating Al toxicity than was CaCO3. Mung bean plants receiving pig manure or wheat straw contained relatively high concentrations of P, Ca and K in their leaves. It is suggested that the beneficial effect of organic manure on mung bean is likely due to decreasing concentrations of monomeric inorganic Al concentrations in soil solution and improvement of mineral nutrition. PMID- 11198176 TI - Enhanced biodegradation of cyclotetramethylenetetranitramine (HMX) under mixed electron-acceptor condition. AB - The biodegradation of cyclotetramethylenetetranitramine, commonly known as 'high melting explosive' (HMX), under various electron-acceptor conditions was investigated using enrichment cultures developed from the anaerobic digester sludge of Thibodaux sewage treatment plant. The results indicated that the HMX was biodegraded under sulfate reducing, nitrate reducing, fermenting, methanogenic, and mixed electron accepting conditions. However, the rates of degradation varied among the various conditions studied. The fastest removal of HMX (from 22 ppm on day 0 to < 0.05 ppm on day 11) was observed under mixed electron-acceptor conditions, followed in order by sulfate reducing, fermenting, methanogenic, and nitrate reducing conditions. Under aerobic conditions, HMX was not biodegraded, which indicated that HMX degradation takes place under anaerobic conditions via reduction. HMX was converted to methanol and chloroform under mixed electron-acceptor conditions. This study showed evidence for HMX degradation under anaerobic conditions in a mixed microbial population system similar to any contaminated field sites, where a heterogeneous population exists. PMID- 11198177 TI - Biodegradation of phenol in a continuous process: comparative study of stirred tank and fluidized-bed bioreactors. AB - The paper presents the main results obtained from the study of the biodegradation process of phenol by a pure culture of Pseudomonas putida ATCC 17484. The experimental work was carried out in two different systems: a stirred tank where cells grew as a suspended culture and a fluidized bed where cells were immobilized within calcium alginate gel beads. The influence of the hydraulic residence time (HRT) and organic loading rate on the removal efficiency of phenol was determined for both bioreactors. Also, the stability of the fluidized-bed bioreactor (FBB) in terms of its ability to withstand sudden phenol overdoses is also reported. Experimental values indicated that both bioreactors showed high phenol degradation efficiencies, higher than 90%, even for a phenol loading rate in the influent as high as 4 g phenol/l day. The FBB showed better performance than the suspended-culture bioreactor due to its better control and because it could operate with lower HRT. PMID- 11198178 TI - Utilization of brewer's yeast cells for the production of food-grade yeast extract. Part 1: Effects of different enzymatic treatments on solid and protein recovery and flavor characteristics. AB - Yeast extract was produced from brewer's yeast of a beer factory by combined enzymatic treatments using endoprotease, exoprotease, 5'-phosphodiesterase, and adenosine monophosphate (AMP)-deaminase. Effects of enzyme combination, enzyme dosages and treatment sequence on the recovery of solid and protein, flavor and compositional characteristics were investigated. Exoprotease dosage strongly affected the recovery of protein and degree of hydrolysis (DH) and sensory characteristics. When the yeast cells were treated using optimal combination of endoprotease and exoprotease (0.6% Protamex and 0.6% Flavourzyme), high solid recovery (48.3-53.1%) and the best flavor profile were obtained. Among various treatment sequences using multiple enzymes, treatment with protease followed by nuclease resulted in the highest 5'-guanosine monophosphate (5'-GMP) content. The optimal concentrations of both 5'-phosphodiesterase and AMP-deaminase were found to be 0.03%. After treatments using optimal combination of enzyme, enzyme dosages and treatment sequence for four enzymes, a high solid yield of 55.1% and 5' nucleotides content of 3.67% were obtained. PMID- 11198179 TI - Influence of thermal treatment on sequential extraction and leaching behaviour of trace metals in a contaminated sewage sludge. AB - The losses of weight and organic matter of a sludge caused by thermal treatments at 180 degrees C, 300 degrees C and 400 degrees C were determined in order to assess how the possibilities of sludge use were influenced. The sludge heated at 180 degrees C lost small amounts of weight and organic matter (9.8%) but the losses from the two other treatments were large enough (92.2% and 99.9% in organic matter) to preclude the use of the sludges as organic amendments. The concentration and potential lability and leachability of Cr, Cu, Fe, Mn, Ni, Pb and Zn in the native sludge and in the thermal-treated sludge samples were studied by means of a five-step chemical fractionation method and a column experiment. As a consequence of heating, the trace metals were more strongly fixed in the treated sludges, as could be seen by the decrease with temperature of the ratio between the sum of the first two sequential-extracted fractions and the residual fraction. The leaching results showed that, for the native sludge, the quantities of studied metals leached were larger than for the sludge heated to 180 degrees C. The order of leachability of metals was the same in both cases, and the same equation could be used to calculate the quantities of metals leached. The amounts of metals leached correlated significantly with the first extracted fraction (exchangeable metals) and an equation could be used to calculate the quantities leached, as a function of that fraction. PMID- 11198180 TI - Physico-chemical properties and productivity of a Nigerian Typic-Haplustult amended with fresh and burnt rice-mill wastes. AB - In order to arrest the declining productivity of the soils in the Abakaliki agro ecological zone of S.E. Nigeria, four levels (12.5, 25.0, 37.5 and 50.0 Mg ha-1) of fresh (FW) and burnt (BW) rice-mill wastes abundant in the area, and a mixture of the waste + NPK and NPK alone were added to the soil (Typic-Haplustult) to evaluate their immediate and residual effects on the productivity of the soil using maize (Zea mays L.) as a test crop. Results showed a significant reduction in bulk density as well as improvements in total porosity and water stable aggregates (WSA > 0.5 mm) at levels > 12.5 Mg ha-1 of the FW amendments. Although both amendments failed to improve the soil pH, significant improvements in soil C, N and BS were obtained at 37.5 Mg ha-1 and above in both amendments. The highest relative increase (TF) of 135.1% and 102.8% in C and N in the first season and 94.4% and 99.3% in the second season were obtained in the FW at 50.0 Mg ha-1. The highest maize grain yields of 2.74 and 2.66 Mg ha-1 were obtained in the waste + NPK mixtures (FW/BW + NPK) in the first season. The residual yield was highest (1.45 Mg ha-1) in the FW amendment at 50.0 Mg ha-1. The results showed that regular and properly planned applications of these wastes can sustain the productivity of soils in this region. PMID- 11198181 TI - Insecticidal properties of volatile extracts of orange peels. AB - Statistical studies using the randomised complete block design with four replicates showed that volatile extracts of two species of orange peel--Citrus sinensis (sweet orange) and Citrus aurantifolia (lime) had insecticidal activity against mosquito, cockroach and housefly. Insecticidal activity was better after 60 min than at 30 min spraying of rooms. Volatile extracts of C. sinensis showed greater insecticidal potency, while the cockroach was the most susceptible to the orange peels among the three insects studied. PMID- 11198182 TI - Co-composting of sugarbeet vinasse: influence of the organic matter nature of the bulking agents used. AB - Two composts were obtained by co-composting of a concentrated depotassified beet vinasse and two agricultural solid residues with different organic matter nature: grape marc (GM; lignin waste) and cotton gin trash (C; cellulosic waste). Composting was carried out in aerated piles with mechanical turning, in controlled conditions during 4 months. After 71 days of composting, a new addition of vinasse similar to the initial addition was made. Changes in temperature, pH and inorganic nitrogen followed a similar path for both mixtures. However, organic matter fractions showed different behaviour depending on the material co-composted with vinasse. Lower organic matter degradation was observed when GM was used as bulking agent due to its high lignin content. No phytotoxicity was detected in the end products. The chemical and physical properties of both vinasse composts suggest their possible use as fertiliser. PMID- 11198183 TI - Bioaugmentation and treatment of cephalexin drug-based pharmaceutical effluent in an upflow anaerobic fluidized bed system. AB - Cephalexin is a constituent of the cephalosporin group used for the treatment of bronchitis and other heart diseases due to its enhanced oral activity. The effluent from these industries contains a disintegrated form of the drug contributing high chemical oxygen demand (COD), volatile solids and organic solvent. A laboratory-scale study was conducted to evaluate the efficiency of a fluidized bed reactor operated under anaerobic condition with bioaugmentation to treat the cephalexin containing pharmaceutical factory effluent. The main objective of the study was to show that bioaugmentation could be used to promote biological treatment to applications where conventional operation might be difficult or unfavourable. The effluent, with COD of 12,000-15,000 mg/l, was diluted and studied in single and multiple inoculation experiments with hydraulic retention times of 3-12 h. The removal efficiency after inoculation from an anaerobic sequencing batch reactor was related to influent concentration, mass of inoculum and hydraulic retention time characterized by calculating the initial food to microorganism ratio. Continuous COD removal efficiency attained a maximum value of 88.5% using bioaugmentation through periodic addition of acclimated cells every 2 days with 30-73.2 g of cells from an off-line enricher-reactor. PMID- 11198184 TI - gamma-Linolenic acid production by solid-state fermentation of Mucorales strains on cereals. AB - Oleaginous fungi of the genus Mucorales were screened for gamma-linolenic acid (GLA) production on solid substrates containing moistened cereals. Cunninghamella elegans CCF 1318 produced the highest yields of GLA when cultivated on barley. Substrate moisture and cultivation temperature proved critical for effective GLA production. Vegetable oil supplied to the cultures improved GLA production. Rotating bottles and plastic bags were used as cultivation vessels to reproduce the conditions found in rotating drums and tray bioreactors, respectively. After 11 days of cultivation at 21 degrees C, C. elegans produced 14.2 mg of GLA per gram of dry substrate, composed of a mixture of barley, spent malt grains (SMG) and peanut oil. GLA represented 15.6% of the total fatty acids in the lipid extract. PMID- 11198185 TI - Repellent activity of Ferronia elephantum Corr. (Rutaceae) leaf extract against Aedes aegypti (L.). AB - The repellent activity of a methanol extract of Ferronia elephantum leaves against Aedes aegypti was studied in the laboratory. The percentage protection in relation to the dose method was used. The repellent activity at 1.0 and 2.5 mg/cm2 concentrations gave 100% protection up to 2.14 +/- 0.16 h and 4.00 +/- 0.24 h, respectively. The total percentage protection of Ferronia elephantum was 45.8% at 1.0 mg/cm2 and 59.0% at 2.5 mg/cm2 for 10 h. PMID- 11198186 TI - Application of the RealAudio package to computerized medical lectures. AB - We created a multimedia system to computerize past lectures using RealAudio software. Physicians, medical researchers and students can browse the contents of lecture slides and handouts with synchronous audio using the Internet. The audience can easily review the most interesting parts of lectures and medical students can listen to complete medical lectures from remote sites with narration and slide depiction, whenever convenient. We have created three multimedia programs; the memorial lecture of a professor's retirement, a new method of hand washing for surgical procedures and a lecture on medical informatics. The cost of this system and the results of the evaluation by medical students are described. The ease of using this application makes it a potentially valuable tool for clinicians and researchers. PMID- 11198187 TI - GASTON: an architecture for the acquisition and execution of clinical guideline application tasks. AB - Recently, studies have shown the benefits of using clinical guidelines in the practice of medicine. There have been numerous efforts to develop clinical decision support systems that support guideline-based care in an automated fashion, covering a wide range of clinical settings and tasks. Despite these efforts, only a few systems progressed beyond the prototype stage and the research laboratory. For guideline-based clinical decision support systems to be successful, a balance must be made between intuitive but imprecise representations usually encountered by most of today's systems and representations that support a strong underlying clinical performance model. The project described in this paper tries to achieve such a balance. It presents the GASTON architecture that contains a set of reusable software components for the application of guidelines, including design-time components to facilitate the guideline authoring process based on guideline representation models along with execution-time components for building decision support systems that incorporate these guidelines. This architecture was used to develop several guideline representation models such as a rule-based representation to model rule-based guidelines and guideline representation models that address more complex tasks. Also, decision support systems that incorporate these models were developed with the architecture. For the representation and application of various classes of guidelines, rules were also viewed as instances of more complex tasks. By identifying similar characteristics of sets of rules, we developed several tasks such as a drug intera ction and drug contraindication task. Based on these models, we have developed and validated guidelines and decision support systems for use in several application domains such as intensive care, family physicians and psychiatry. In order to be able to represent more complex time-oriented plans, new guideline representation models are being developed. PMID- 11198188 TI - Development of an Internet Security Policy for health care establishments. AB - The Internet provides unprecedented opportunities for interaction and data sharing among health care providers, patients and researchers. However, the advantages provided by the Internet come with a significantly greater element of risk to the confidentiality and integrity of information. This paper defines the basic security requirements that must be addressed in order to use the Internet to safely transmit patient and/or other sensitive Health Care information. It describes a suitable Internet Security Policy for Health Care Establishments and provides the set of technical measures that are needed for its implementation. The proposed security policy and technical approaches have been based on an extensive study of the related recommendations from the security and standard groups both in EU amid USA and our related work and experience. The results have been utilized in the framework of the Intranet Health Clinic project, where the use of the Internet for the transmission of sensitive Health Care information is of vital importance. PMID- 11198189 TI - MASTOS: Mammography Simulation Tool for design Optimization Studies. AB - Mammography is a high quality imaging technique for the detection of breast lesions, which requires dedicated equipment and optimum operation. The design parameters of a mammography unit have to be decided and evaluated before the construction of such a high cost of apparatus. The optimum operational parameters also must be defined well before the real breast examination. MASTOS is a software package, based on Monte Carlo methods, that is designed to be used as a simulation tool in mammography. The input consists of the parameters that have to be specified when using a mammography unit, and also the parameters specifying the shape and composition of the breast phantom. In addition, the input may specify parameters needed in the design of a new mammographic apparatus. The main output of the simulation is a mammographic image and calculations of various factors that describe the image quality. The Monte Carlo simulation code is PC based and is driven by an outer shell of a graphical user interface. The entire software package is a simulation tool for mammography and can be applied in basic research and/or in training in the fields of medical physics and biomedical engineering as well as in the performance evaluation of new designs of mammography units and in the determination of optimum standards for the operational parameters of a mammography unit. PMID- 11198190 TI - Molecular organization of excitatory chemical synapses in the mammalian brain. AB - Chemical synapses are highly specialized cell-cell junctions designed for efficient signaling between nerve cells. Distinct cytoskeletal matrices are assembled at either side of the synaptic junction. The presynaptic cytomatrix at the active zone (CAZ) defines and organizes the site of neurotransmitter release from presynaptic nerve terminals. The postsynaptic density (PSD) tethers neurotransmitter receptors and the postsynaptic signal transduction machinery. Recent progress in the identification and characterization of novel CAZ and PSD components has revealed new insights into the molecular organization and assembly mechanisms of the synaptic neurotransmission apparatus. On the presynaptic side, Bassoon and Piccolo, two related giant proteins, are crucially involved in scaffolding the CAZ. On the postsynaptic side, two families of multidomain adaptor proteins, the MAGuKs (membrane-associated guanylate kinase homologs) and the ProSAP (proline-rich synapse-associated protein, also termed Shank) family members are thought to be major organizing molecules of the PSD. PMID- 11198191 TI - The Sun's normal modes of oscillation. PMID- 11198192 TI - Three dimensional path integration in the house mouse (Mus domestica). AB - Previous studies have explored two-dimensional path integration in rodents by recording responses to passive rotation on a horizontal plane. This study adds the element of passive rotation in a vertical plane, necessitating the mouse to integrate positional information from three dimensions. Mice were trained to climb a wire mesh joining two horizontal planes. The whole arena was rotated 90 degrees while the mouse was vertically oriented as it moved between planes. Rotation was conducted both clockwise and counter-clockwise, controls being provided by rotation of the arena while the mouse was in its nest-box. All 16 mice tested altered their direction of travel subsequent to rotation in the vertical plane, compensating with a change in their path on the following horizontal plane. PMID- 11198193 TI - Involvement of opioid peptides in the regulation of reproduction in the prawn Penaeus indicus. AB - The possible involvement of an endogenous opioid system in the regulation of ovarian development in the prawn Penaeus indicus was investigated. Injection of leucine-enkephalin significantly increased the ovarian index and oocyte diameter in a dose-dependent manner. In contrast, injection of methionine-enkephalin significantly decreased the ovarian index and oocyte diameters. These results provide evidence to support the hypothesis that an opioid system is involved in the regulation of reproduction in crustaceans. PMID- 11198194 TI - Enzymatic activation of lignin leads to an unexpected copolymerization with carbohydrates. PMID- 11198195 TI - A new type of infrared organ in the Australian "fire-beetle" Merimna atrata (Coleoptera: Buprestidae). AB - The Australian buprestid beetle Merimna atrata (Coleoptera: Buprestidae) approaches forest fires because its larvae develop in freshly burnt wood. So far nothing is known about possible sensory systems enabling the beetles to detect fires and to cope with the thermal environment close to the flames. We found that M. atrata has two pairs of infrared (IR) organs on the ventrolateral sides of the abdomen. Each IR organ consists of a specialized IR-absorbing area which is innervated by one thermosensitive multipolar neuron. The primary dendritic branches ramify into more than 800 closely packed terminal endings which contain a large number of mitochondria. We called the special morphology of the dendritic region a terminal dendritic mass. The type of IR receptor found in M. atrata is unique in insects and can best be compared with the IR organs of boid snakes. PMID- 11198196 TI - Non-discriminatory incorporation of L-phenylalanine and L-tyrosine into cinnamoyl part of mulberroside A, a stilbene di-glucoside, in Morus alba cell cultures. PMID- 11198197 TI - Agro-predation: usurpation of attine fungus gardens by Megalomyrmex ants. AB - A new ant species of Megalomyrmex conducts mass raids to usurp gardens of the fungus-growing ant Cyphomyrmex longiscapus, then lives in the gardens and consumes the cultivated fungus. Unlike attine ants, however, Megalomyrmex sp. does not forage for substrate to manure the gardens; therefore, when gardens become depleted, Megalomyrmex sp. must locate and usurp new gardens. Megalomyrmex sp. workers feed their larvae with attine brood, but only after removing the fungal mycelium that covers the attine larval integument, suggesting that this fungal coat may provide partial protection against other predators. Unlike other known Megalomyrmex species, which coexist as social parasites in attine colonies, Megalomyrmex sp. expels its attine hosts during the garden raids. Megalomyrmex sp. thus maintains a unique agro-predatory lifestyle that is described here for the first time. PMID- 11198198 TI - Low chitinase activity in Acacia myrmecophytes: a potential trade-off between biotic and chemical defences? AB - We determined chitinase activity in leaves of four myrmecophytic and four non myrmecophytic leguminous species at the plants' natural growing sites in Mexico. Myrmecophytic plants (or 'ant plants') have obligate mutualisms with ants protecting them against herbivores and pathogenic fungi. Plant chitinases can be considered a reliable measure of plant resistance to pathogenic fungi. The myrmecophytic Acacia species, which were colonised by mutualistic ants, exhibited at least six-fold lower levels of chitinase activity compared with the non myrmecophytic Acacia farnesiana and three other non-myrmecophytes. Though belonging to different phylogenetic groups, the myrmecophytic Acacia species formed one distinct group in the data set, which was clearly separated from the non-myrmecophytic species. These findings allowed for comparison between two recent hypotheses that attempt to explain low chitinase activity in ant plants. Most probably, chitinases are reduced in myrmecophytic plant species because these are effectively defended indirectly due to their symbiosis with mutualistic ants. PMID- 11198199 TI - A molecular phylogenetic analysis of the neotropical dart-poison frog genus Phyllobates (Amphibia: Dendrobatidae). AB - A phylogenetic analysis of the Neotropical dart-poison frogs, genus Phyllobates, was performed based on mitochondrial cytochrome b sequences. Members of Phyllobates from South and Central America were found to form each an evolutionary lineage. Among the South American lineage, species with uniform dorsal coloration as adults form a derived monophyletic clade. PMID- 11198200 TI - Communal peeing: a new mode of flood control in ants. AB - The behavioral response of the obligate bamboo-nesting ant Cataulacus muticus to nest flooding was studied in a perhumid tropical rainforest in Malaysia and in the laboratory. The hollow internodes of giant bamboo, in which C. muticus exclusively nests, are prone to flooding by heavy rains. The ants showed a two graded response to flooding. During heavy rain workers block the nest entrances with their heads to reduce water influx. However, rainwater may still intrude into the nest chamber. The ants respond by drinking the water, leaving the nest and excreting water droplets on the outer stem surface. This cooperative 'peeing' behavior is a new survival mechanism adaptive to the ants' nesting ecology. Laboratory experiments conducted with two other Cataulacus species, C. catuvolcus colonizing small dead twigs and C. horridus inhabiting rotten wood, did not reveal any form of water-bailing behavior. PMID- 11198201 TI - Variation in the heritability and evolvability of human lifespan. AB - The heritability and evolvability of lifespan in two socioeconomically different groups of humans, including birth cohorts for 1600-1800s, were investigated. Among the aristocratic Europeans, the heritability estimates based on offspring mother regressions ranged from 0.46 to 0.89, while the estimates based on offspring-father regressions varied from 0.23 to 0.59. However, the rural Finns possessed either no inheritable component or a clearly lower level of heritability than did the aristocrats, the estimates ranging from 0 to 0.40, depending on the method used. The additive genetic coefficients of variation and standardized evolvabilities were high in the aristocrats, especially in the data set including all data instead of limiting the data to the older age group. Among rural Finns, the values were considerably lower. PMID- 11198202 TI - Correlation between MRI findings and long-term outcome in patients with severe brain trauma. AB - Our aim was to relate MRI findings in patients with severe traumatic brain injury (TBI) to clinical severity and long-term outcome. We studied 37 patients with severe TBI, who were submitted to clinical assessment for disability and cognition and to MRI 60-90 days after trauma. Clinical assessment was also performed 3, 6 and 12 months later. The number and volume of lesions in various cerebral structures were calculated semiautomatically from FLAIR and fast field echo images. Possible correlations between total and regional lesion volume and clinical deficits were then investigated. The frontal and temporal lobes were most frequently involved. Total lesion volume on FLAIR images correlated significantly with clinical outcome, whereas that on FFE images did not. Regional analysis showed that FLAIR lesion volume in the corpus callosum correlated significantly with scores on disability and cognition scales at the first clinical assessment. FLAIR lesion volume in the frontal lobes correlated significantly with clinical scores 1 year later. PMID- 11198203 TI - Poststenotic signal attenuation on 3D phase-contrast MR angiography: a useful finding in haemodynamically significant carotid artery stenosis. AB - We performed blinded visual evaluation of MR angiography (MRA) films in 44 patients with unilateral carotid artery stenosis to determine whether a flow gap and poststenotic signal attenuation on 3D-PC MRA were useful signs of severe carotid artery stenosis. Although nine patients with a flow gap alone had various degrees of stenosis ranging from 22.2 to 77.3% without any decrease in regional cerebral blood flow (rCBF), 13 patients with both a flow gap and poststenotic signal attenuation had severe stenoses of 80% or more, with a definite decrease in baseline rCBF. The presence of both a flow gap and poststenotic signal attenuation on 3D-PC MRA appeared to be a reliable marker of severe carotid artery stenosis with a decrease in rCBF. PMID- 11198204 TI - Gadolinium-myelocisternography for cerebrospinal fluid rhinorrhoea. AB - Knowledge of the exact site of leakage of cerebrospinal fluid CSF leakage is important for planning surgery. We report our experience with myelocisternography with Gd-DTPA. We decided that intrathecal use of this contrast medium was justified in selected cases when other techniques have failed. After we had given detailed information to four patients with CSF leakage, they underwent five examinations. The images were interpreted by comparing those before and after injection. In all cases the contrast medium arrived at the basal cisterns, giving high contrast against adjacent structures. All patients tolerated the examination without complications or any indication of side effects. PMID- 11198205 TI - Cavernous dilatation of mesencephalic Virchow-Robin spaces with obstructive hydrocephalus. AB - We describe two patients with mild ventricular dilatation, shown to have cystic spaces in the midbrain, which we interpreted as greatly enlarged Virchow-Robin spaces. We discuss the pathophysiology and the possible relations to the mild hydrocephalus. PMID- 11198206 TI - Qualitative and quantitative volumetric evaluation of the efficacy of intravenous immunoglobulin in multiple sclerosis: preliminary report. AB - We conducted a double-blind, placebo-controlled study in 13 patients (aged 22 to 54 years) with relapsing-remitting multiple sclerosis (MS). They were randomly assigned to receive a loading dose of immunoglobulin IgG, 0.4 g/kg body weight/day for 5 consecutive days, followed by single booster doses of 0.4 g/kg/day, or placebo, once a month for 9 months. MRI was obtained before and during the 3rd and 6th months of treatment; examinations in the 9th and 12th months were planned. Qualitative and quantitative blinded assessments were performed. There were seven patients who received active treatment and six who received placebo. Statistical analysis was performed by the Wilcoxon test. A decrease in the size and number of lesions was observed on MRI in five patients (71%) in the treatment group, and in two (33%) of the placebo group at 3-month follow-up. At 6 months follow-up MRI, a decrease in the amount of lesions was observed in all patients treated with i.v. IgG, and in two (33%) of the placebo group; four patients (66%) receiving placebo showed an increase. Quantitative analysis showed a statistically significant decrease in the volume of lesions in treatment group at both 3 and 6 month follow-up. There was no statistically significant change in the placebo group. PMID- 11198207 TI - Idiopathic granulomatous hypophysitis: are there reliable, constant radiological and clinical diagnostic criterias? AB - Idiopathic granulomatous hypophysitis is a rare inflammatory disease of unknown aetiology; few cases are reported. We review the clinical presentation and radiological characteristics of these cases and our own experience with three new surgical cases, to determine diagnostic criteria. MRI of three cases revealed sellar lesions extending into the chiasmatic cistern. Their shape varied, from dumbbell to spherical and elliptical. All were isointense with the brain on T1 weighted images and gave heterogeneously high signal on T2-weighted images. Contrast enhancement was homogeneous in one case and heterogeneous in another. The pituitary stalk could not be identified. There was no dural enhancement. The sphenoid sinus mucosa was thickened in two cases and normal in one. PMID- 11198208 TI - Reversible posterior leukoencephalopathy after combination chemotherapy. AB - We describe a young woman with Burkitt's lymphoma, treated with intravenous adriamycine and cyclophosphamide and intrathecal cytarabine. She developed a reversible posterior leukoencephalopathy syndrome (RPLS) with typical MRI findings. Diffusion-weighted images during the first days after the onset of symptoms predicted a small irreversible lesion in the frontal lobe, verified on T2-weighted images 1 month later. The patient showed full recovery after high dose steroid treatment. PMID- 11198209 TI - Transcranial colour Doppler sonography in emergency management of intracerebral haemorrhage caused by an arteriovenous malformation: case report. AB - We present a case which demonstrates the use of transcranial colour Doppler (TCCD) sonography in screening for an underlying arteriovenous malformation (AVM) in a middle-aged hypertensive patient with a spontaneous thalamic haematoma. The AVM was not detected on emergency CT but its presence, site and shape were demonstrated by TCCD, in the presence of a massive cerebral haemorrhage and acute intracranial hypertension. PMID- 11198210 TI - A case of ochronosis: MRI of the lumbar spine. AB - We present the MRI features of the lumbar spine in a patient with ochronosis. PMID- 11198211 TI - Perirolandic hypoperfusion on single-photon emission computed tomography in term infants with perinatal asphyxia: comparison with MRI and clinical findings. AB - We describe the findings on single-photon emission computed tomography (SPECT) in patients with perinatal asphyxia at term, with perirolandic cortico-subcortical changes on MRI, and to correlate them with clinical features. SPECT of 7 patients was obtained after injection of 185-370 MBq of Tc-99m-ECD (ethyl cysteinate dimer). The patients had spastic quadriplegia (7/7) with perinatal asphyxia (6/7) at term (7/7). The results were correlated with the MRI findings. Hypoperfusion of the perirolandic cortex was clearly seen on SPECT in all patients, even in two with subtle changes on MRI. SPECT demonstrated a more extensive area of involvement than MRI, notably in the cerebellum (in 4), the thalamus (in 7) and basal ganglia (in 5), where MRI failed to show any abnormalities. PMID- 11198212 TI - Subacute sclerosing panencephalitis: brain stem involvement in a peculiar pattern. AB - The most common pattern in subacute sclerosing panencephalitis, is in the cerebral hemisphere white matter on T2-weighted images with or without atrophy. Brain-stem lesions are rare. We report brain-stem involvement in two children with subacute sclerosing panencephalitis. A peculiar pattern, with involvement of the pons with extension to both middle cerebellar peduncles and substantia nigra but sparing the pontine tegmentum, is suggested. PMID- 11198213 TI - MRI of ranulas. AB - We reviewed the MRI of 20 patients with a ranula (8 simple and 12 plunging) and ten with other cystic masses in the floor of the mouth and/or suprahyoid portion of the neck (three haemangiomas, two neuromas, one monomorphic adenoma, one lipoma, two lateral cervical cysts and one dermoid cyst). Histological diagnoses were obtained in all cases with the exception of one presumed haemangioma. Ranulas were all well-defined, homogeneous masses giving low signal on T1- and markedly high signal on T2-weighted images. While simple ranulas were all confined to the sublingual space, plunging ranulas were centered on the submandibular space and tended to spill into one or more adjacent spaces. They extended into the sublingual space anteriorly (producing a so-called tail sign) in eight of 12 cases and into the parapharyngeal space superiorly in five. Although they sometimes filled a considerable part of the parapharyngeal space, displacement of surrounding muscles or vessels was usually slight, which was thought to reflect the nature of extravasation pseudocysts. All other cystic masses in our study had one or more MRI finding different from those of ranulas and could be easily differentiated from them. PMID- 11198214 TI - A thyroglossal duct cyst with calcification. AB - We report a thyroglossal duct cyst with calcification, the second case in the world literature. The ultrasound and CT findings are described and we highlight the differential diagnosis. PMID- 11198215 TI - Combined endovascular therapy of ruptured aneurysms and cerebral vasospasm. AB - We describe two patients with subarachnoid haemorrhage due to a ruptured intracranial aneurysm and severe symptomatic vasospasm. The aneurysm was occluded with detachable coils followed by intra-arterial infusion of papaverine to treat vasospasm as an one-stage procedure. There was significant resolution of the vasospasm. The long-term clinical outcome in one patient was excellent, the other still has minor deficits. Combined endovascular aneurysm therapy followed by intra-arterial spasmolysis with papaverine is a technically feasible therapeutic alternative in patients with symptomatic vasospasm. PMID- 11198216 TI - An unusual association of intracranial aneurysms and oesophageal duplication in a case of Klippel-Trenaunay syndrome. AB - The Klippel-Trenaunay syndrome (KTS) is a congenital disorder resulting from a mesodermal abnormality, characterised by cutaneous capillary haemangiomas, hypertrophy of bone and soft tissues and varicose veins. The presence of intracranial aneurysms has rarely been described, while oesophageal duplication has not been reported previously. We describe a patient with the KTS with both there additional abnormalities, which could be explained by a postulated mosaic gene abnormality. PMID- 11198217 TI - Chrysotile-induced cell transformation and transcriptional changes of c-myc oncogene in human embryo lung cells. AB - It has been verified that asbestos induce neoplastic transformation of several rodent cell lines in vitro. Very little information is available, however, on asbestos-induced human cell line transformation and oncogene activation in the development of asbestos-induced cell transformation. This study was designed to investigate the induction of cell transformation and transcriptional changes of the c-myc oncogene by chrysotile asbestos fibers (CAF) in human embryo lung (HEL) cells. Surface-modified CAF soaked in aluminium citrate (AC), rare earth compounds (REC) or sodium selenite (SS) solutions were used to observe the effects of surface modification on chrysotile-induced cell transformation and transcriptional changes in the c-myc oncogene. The results showed that the natural CAF caused dose-dependent increases in transformed foci, along with increased transcription of the c-myc oncogene in HEL cells, while the pretreated CAF induced fewer transformed foci and less c-myc oncogene transcription than the natural CAF. The percent inhibition of equivalent AC, REC and SS were 38.9%, 50.0%, 33.3% (for transformation focus), 81.6%, 69.5%, 89.9% (for c-myc oncogene transcription), respectively. These results indicated that CAF may induce cell transformation and transcriptional changes and that the carcinogenicity of CAF might be reduced by pretreatment of CAF with the above-mentioned compounds. PMID- 11198218 TI - The effects on cell growth of tea polyphenols acting as a strong anti peroxidatant and an inhibitor of apoptosis in primary cultured rat skin cells. AB - Studies during the past few years have indicated an inhibitory effect of green tea or tea polyphenols on tumorigenesis in animal and even in human. The purpose of this study was to observe the possible effects of tea polyphenols on skin cell growth and on apoptosis in rat primary cultured keratinocytes and fibroblasts. The release of a cell plasma enzyme (LDH), lipid peroxidation products (MDA production), and GSH-Px (glutathione peroxidase) into the medium in cultured cells was determined after treatment with tea polyphenols in a primary culture of skin cells. The percentage of cells in each cell cycle phase and in apoptosis were assayed by flow cytometry (FCM). Tea polyphenols may have a beneficial effect on skin cells at concentrations from 0.05% to 0.1%, showing a dose dependent decrease in LDH, MDA (malondialdehyde) production, and a significant dose-dependent increase in GSH-Px and cell number. These effects were more obvious after exposure for 24 h than after 12 h. The results indicate that tea polyphenols may stabilize and protect the cell membrane against the release of cell plasma enzyme LDH, and its anti-peroxidation effect is also important for cell growth. FCM analysis revealed that treatment with 0.01% to 0.1% tea polyphenols decreased the percentage of cells in the G1/G0 (quiescent) phase from 81.32% to 74.38%, and increased the percentage of cells in S and G2/M phase from 9.87% to 15.26%, and from 6.51% to 10.36%, respectively. Tea polyphenols also increased the value of PI (proliferation index) from 18.17 to 25.62. At the same time it decreased the percentage of apoptosis from 27.10% to 17.97%, which indicates that green tea stimulates cell growth and inhibits the occurrence of apoptosis. Our results indicate that tea polyphenols are effective anti-oxidants and also inhibit apoptosis, which may improve the proliferative capacity of primary skin cells in vitro. PMID- 11198219 TI - Adaptive response of thymocyte apoptosis and cell cycle progression induced by low dose X-ray irradiation in mice. AB - The dose-effect of adaptive response of thymocyte apoptosis and cell cycle progression induced by whole-body X-ray irradiation (WBI) was studied in male Kunming mice. The inductive doses (D1) were 25, 50, 75, 100 or 200 mGy 6 h before the challenging doses (D2) of 1.0, 1.5 or 2.0 Gy. The changes in the percentages of the thymocyte apoptotic bodies (TAB) and the cells in different phases of cell cycle were measured with flow cytometry. The percentages of TAB decreased, the arrests of G1 and G2 + M phases diminished, and the cells of DNA synthesis of S phase increased when the D1 + D2 groups was compared with the D2 groups. When D1 was 200 mGy, the adaptive response of thymocyte apoptosis and cell cycle progression were no longer induced by low dose radiation (LDR). In addition, the extracellular fluid from the splenocytes were cultured with Con A for 48 h in vitro 24 h after 75 mGy WBI was placed in the murine thymocyte suspension from mice irradiated with 2.0 Gy WBI and co-incubated. The thymocyte apoptosis decreased. Especially, noteworthy was that the percentages of TAB after the incubation for 72 h were significantly lower than those in 2.0 Gy irradiated thymocytes (P < 0.05). These results indicate that when the mice were irradiated with 25-100 mGy (D1, 12.5 mGy/min) 6 h before 1.0-2.0 Gy (D2, 0.287 Gy/min) exposure, an adaptive response of thymocyte apoptosis and cell cycle progression may be induced under the condition of WBI, and LDR (75 mGy) may change the microenvironment of immune cells and decrease the thymocyte apoptosis. PMID- 11198220 TI - The association of BMI and WHR on blood pressure levels and prevalence of hypertension in middle-aged and elderly people in rural China. AB - The purpose of this study was to examine the effects of BMI (Body Mass Index) and WHR (Waist Hip Ratio) on average blood pressure and the prevalence of hypertension in middle-aged and elderly population in rural China. A total of 12955 subjects including 6276 males and 6688 females over 40 years of age were surveyed. Height, weight, waist circumference, hip circumference and blood pressure were measured. The association of BMI and WHR on average blood pressure levels and prevalence of hypertension were analyzed by dividing BMI and WHR into tertiles. The average blood pressure levels and the prevalence of hypertension in males and females increased significantly with the increase of BMI or WHR (P < 0.01), as well as with the increase of both of them (P < 0.01). The average blood pressure and the prevalence of hypertension stopped increasing when WHR was > or = 0.76, suggesting that WHR > or = 0.80 could be used as a cut-off value for the prediction of hypertension risk for both males and females. Therefore hypertension could be effectively prevented and controlled by controlling BMI and WHR. PMID- 11198221 TI - Comparative assay of Hepatitis B and C virus infection markers by different assay kits. AB - In order to compare sensitivity of EIA and RIA assay kits for hepatitis B and C virus (HBV and HCV, respectively) infection markers, 100 serum samples in total were collected form 50 adult women each in urban and rural areas in northeast China. The number of positive cases to the three infection markers on HBV (i.e., HBsAg+, anti-HBs+, and anti-HBc+) and the one on HCV (anti-HCV+) were examined in two laboratories, i.e., in Laboratory A with EIA kits produced in China and in Laboratory B with RIA kits. HCV infection positivity (anti-HCV+) was examined by EIA kits in both laboratories, but from different sources in and outside of China, respectively. The assay in Laboratory A gave 2 HBsAg+ cases out of the 100 cases examined, whereas there were 9 positive cases in Laboratory B. In contrast, 19 cases were positive to anti-HCV when examined in Laboratory A, and there were 3 cases in Laboratory B. Thus, the kits used in Laboratory A gave fewer HBsAg+ and more anti-HCV+ cases than the kits used in Laboratory B. The prevalence of anti-HBs+ or anti-HBc+ and cases did not differ when assayed in the two laboratories with EIA and RIA kits, respectively. The agreement of positive and negative findings between the two sets of testing were 93%, 93%, 93%, 86% and 82% for HBsAg, anti-HBs, anti-HBc, HBV (i.e., either positive to anyone of the three markers or negative to all three markers), and anti-HCV, respectively. The implication of the observation on epidemiology on HBV and HCV infection prevalence was discussed. PMID- 11198222 TI - Chelation in metal intoxication. XLIV: Efficacy of alpha-mercapto-beta-(5 substituted, 2-furyl) acrylic acids in mobilizing intracellularly bound cadmium in rat. AB - The efficacy of alpha-mercapto-beta-(2-furyl) acrylic acid (MFA), alpha-mercapto beta-(5-sodiumsulfonate, 2-furyl) acrylic acid (MSFA) and alpha-mercapto-beta-(5 acetoxymethyl, 2-furyl) acrylic acid (MAFA) to mobilize intracellularly bound cadmium in liver and kidney was investigated in rats pre-exposed to cadmium. MFA was effective in reducing cadmium levels of hepatic and renal supernatant cytosolic fraction (SCF) while MSFA and MAFA were effective in lowering cadmium levels of renal SCF and hepatic SCF respectively. All the chelating agents also enhanced the excretion of cadmium more in feces than in urine. However, substitution on the furan ring lowered cadmium mobilizing efficacy of the parent compound, MFA. The treatment with MFA did not affect the status of endogenous zinc and copper while the treatment with MSFA and MAFA enhanced their excretion. MSFA increased hepatic and renal zinc and renal copper while MAFA increased their copper levels. PMID- 11198223 TI - Effects of black tea extract on transplantable and solid tumors in Swiss albino mice. AB - The chemopreventive effects of green tea and its polyphenols are well documented in the literature. Epidemiological studies have suggested that green tea consumption might be effective in the prevention of certain human cancers. About 80% of the tea is consumed as black tea. Limited studies have been carried out to assess the usefulness of black tea as anti-carcinogen. The present set of investigations were initiated to study the anti-tumorigenic potential of aqueous black tea extract (ATE) in Swiss albino mice in in vivo animal bioassay, using 7, 12 dimethyl-benzanthracene (DMBA) as carcinogen. In the experimental group, 2% ATE was given orally as sole source of drinking water, while the control were allowed to drink normal water, ad lib. The results revealed that drinking of 2% ATE could effectively inhibit the onset of tumorigenesis, cumulative number of tumors and average number of tumors per mouse. In ATE drinking group 44% animals remained tumor free till the termination of experiment, i.e. 26 weeks. In the second set of experiment the preventive efficacy of 2% ATE of different cultivars of black tea, viz orthodox, CTC and dust were tested in Ehrlich Ascites (EA) tumor bearing mice. The preventive effects of ATE were observed in terms of increased life span (ILS). All the cultivars of tea showed more than 25% increase in life span of the animals. Cytotoxic effect of various doses of all three cultivars of black tea was also observed in vitro on EA cells. PMID- 11198224 TI - Upgrading of industrial wastewater treatment units at automobile industry. PMID- 11198225 TI - Sulphur mustard induced oxidative stress and its prevention by sodium 2,3 dimercapto propane sulphonic acid (DMPS) in mice. AB - Sulphur mustard [bis(2-chloro ethyl) sulfide] (SM), a bifunctional alkylating agent has been frequently used as a chemical warfare agent. In the present study, the effects of sodium 2-3-dimercaptopropane sulphonic acid (DMPS) on some biochemical and histological parameters in mice, exposed to 1/4LC50 concentration of SM vapor (10.5 mg/m3) were examined over a period of seven days. Exposure of SM resulted in a significant loss of blood, hepatic and pulmonary glutathione (GSH) and an elevation of hepatic and pulmonary oxidized glutathione (GSSG). These biochemical changes were accompanied by a number of histopathological alterations. The most prominent was congestion and degeneration in viscera and obliteration of chromatin material. These biochemical and histopathological changes were less marked in animals pre-administered with DMPS followed by DMPS exposure indicating some protective value of the thiol (DMPS) against SM induced oxidative injury in mice. PMID- 11198226 TI - Object recognition and image understanding: theories of everything? PMID- 11198227 TI - The architecture of visual cortex and inferential processes in vision. AB - This paper is organised approximately into two halves. In the first half, I review evidence about the structure of the visual system, and I use that evidence to frame what I think are widely held but often implicit ideas about how it works, namely that vision is principally analysis of retinal input. These ideas have been strongly influenced by engineering approaches; form a default view of the visual system that suffuses all the language used to describe it (at least in visual neuroscience); and are to some extent supported by the structural evidence. In the second half, I explore some inconvenient facts from neuroanatomy and neurophysiology which are quite uncomfortable for the traditional view. I then set out a contrary view of how structure and function are linked in the visual system, which is a neurobiological variety of the quite developed view in psychophysics that vision is better understood as knowledge-rich inference. Finally, I explore some of the ramifications of this view for neurophysiological understanding of how the visual system might operate during normal vision. PMID- 11198228 TI - Mechanisms of visual object recognition studied in monkeys. AB - Cells in area TE of the inferotemporal cortex of the monkey brain selectively respond to various moderately complex object-features, and those responding to similar features cluster in a columnar region elongated vertical to the cortical surface. Although cells within a column respond to similar features, their selectivity is not identical. The data of optical imaging in TE have suggested that the borders between neighboring columns are not discrete but columns representing related features overlap one another. We have also found, by training adult monkeys for discrimination of a specific set of shapes, that such a long-term training increases the proportion of TE cells responding to the shapes used in the training even in the adult. The data suggested that TE plays important roles in discrimination of complex shapes and in visual expert learning of discriminating a certain class of objects in the adult. PMID- 11198229 TI - Object recognition: holistic representations in the monkey brain. AB - Cognitive-psychological and neuropsychological studies suggest that the human brain processes facial information in a distinct manner, relying on mechanisms that are anatomically and functionally different from those underlying the recognition of other objects. Face recognition, for instance, can be disrupted selectively as a result of localized brain damage, and relies strongly on holistic information rather than on the mere processing of local features. Similarly, in the non-human primate, distinct neocortical and limbic structures have cell populations responding specifically to face stimuli and only weakly to other visual patterns. Moreover, such cells tend to respond to the entire configuration of a face rather than to individual facial features. But are faces the only objects represented in this way? Here I present some evidence suggesting that at least one aspect of facial processing, the processing of holistic information, may be employed by the primate brain when recognizing any arbitrary homogeneous class of even artificial objects, which the monkey has to individually learn, remember, and recognize again and again from among a large number of distractors sharing a number of common features with the target. Acquiring such an expertise can induce configurational selectivity in the response of neurons in the visual system. Our findings suggests that regarding their neural encoding faces are unlikely to be 'special', but they rather are the default 'special class' of the primate visual system. PMID- 11198230 TI - Disruption of space perception due to cortical lesions. AB - Space control has for a long time been considered a unitary function. The structure associated with this function was the right parietal lobe. Hemispheric specialization for space appeared to make it automatically a human-specific function. However, recent primate research shows different regions of the parietal lobes to be differently involved with space control. A review of the literature, together with own cases shows that there is ample evidence of a modular organization of space control in humans on the basis of specific deficits subsequent to circumscribed cerebral lesions. Lesions influence differentially retinotopic, spatiotopic, egocentric, and allocentric frames of references. They also influence differentially the attention to far or near space, or to global or local features of space. Moreover, preattentive processes can be studied in the neglected hemispace of humans and prove to be sensible to the meaning of visual stimuli. Space representation and attentional mechanisms that seem to operate on these representations are organized in our brain in a very modular fashion, similar to the modularity of visual submodalities. There is probably not a unified space representation in the parietal lobes, but distributed functional modules. Thus, the study of visual optic recognition, either by the brain or by machines, is inconceivable without considering space, attention and awareness. PMID- 11198231 TI - A geometric view on early and middle level visual coding. AB - As opposed to dealing with the geometry of objects in the 3D world, this paper considers the geometry of the visual input itself, i.e. the geometry of the spatio-temporal hypersurface defined by image intensity as a function of two spatial coordinates and time. The results show how the Riemann curvature tensor of this hypersurface represents speed and direction of motion, and thereby allows to predict global motion percepts and properties of MT neurons. It is argued that important aspects of early and middle level visual coding may be understood as resulting from basic geometric processing of the spatio-temporal visual input. Finally, applications show that the approach can improve the computation of motion. PMID- 11198232 TI - Object and scene analysis by saccadic eye-movements: an investigation with higher order statistics. AB - Based on an information theoretical approach, we investigate feature selection processes in saccadic object and scene analysis. Saccadic eye movements of human observers are recorded for a variety of natural and artificial test images. These experimental data are used for a statistical evaluation of the fixated image regions. Analysis of second-order statistics indicates that regions with higher spatial variance have a higher probability to be fixated, but no significant differences beyond these variance effects could be found at the level of power spectra. By contrast, an investigation with higher-order statistics, as reflected in the bispectral density, yielded clear structural differences between the image regions selected by saccadic eye movements as opposed to regions selected by a random process. These results indicate that nonredundant, intrinsically two dimensional image features like curved lines and edges, occlusions, isolated spots, etc. play an important role in the saccadic selection process which must be integrated with top-down knowledge to fully predict object and scene analysis by human observers. PMID- 11198233 TI - Vision as temporal trace. AB - Most current models of human and animal vision assume that the processes of vision involve 2D (or even 3D) internal representations of the external world--an iconic representation. Within these models, recognition involves some form of lineal, areal or volumetric comparison of these internal representations (either learned or innate) with current sensory inputs. However, this view has recently come under criticism. In this paper, a neural model of vision is explored in which this iconic world view is replaced by a temporally ordered trace of (essentially) local features. The model employs hierarchical, recurrently linked, self-organizing topological maps. PMID- 11198234 TI - Dynamics and context dependence of visual category learning. AB - Visual category learning by humans is observed within a paradigm of supervised learning. Mental representations for recognition are reconstructed from the observed data structures by fitting to them predicted classification data obtained from similarity-based models of recognition on the one hand and machine vision systems for image understanding on the other hand. These principles are illustrated with examples concerning the dynamics and the dependence on context of processes of category learning. PMID- 11198235 TI - Recognizing depth-rotated objects: a review of recent research and theory. AB - Many of the phenomena of object classification can be derived from a representation specifying a nonaccidental characterization of an object's parts (geons) and relations, termed a geon structural description (GSD). Such a representation: (a) enables the facile recognition of depth-rotated objects, even when they are novel, (b) provides the information that is employed not only to distinguish basic-level but also highly similar members of subordinate-level classes, and (c) enables mapping onto verbal and object-reasoning structures. Recent psychophysical and neural investigations of object recognition have provided additional support to this theory of object representation. PMID- 11198236 TI - (Coarse coding of shape fragments) + (retinotopy) approximately = representation of structure. AB - The ability to deal with object structure--to determine what is where in a given object, rather than merely to categorize or identify it--has been hitherto considered the prerogative of 'structural description' approaches, which represent shapes as categorical compositions of generic parts taken from a small alphabet. In this note, we propose a simple extension to a theoretically motivated and extensively tested appearance-based model of recognition and categorization, which should make it capable of representing object structure. We describe a pilot implementation of the extended model, survey independent evidence supporting its modus operandi, and outline a research program focused on achieving a range of object processing capabilities, including reasoning about structure, within a unified appearance-based framework. PMID- 11198237 TI - Perception, representation and recognition: a holistic view of recognition. AB - It is clear that humans have mental representations of their spatial environments and that these representations are useful, if not essential, in a wide variety of cognitive tasks such as identification of landmarks and objects, guiding actions and navigation and in directing spatial awareness and attention. Determining the properties of mental representation has long been a contentious issue (see Pinker, 1984). One method of probing the nature of human representation is by studying the extent to which representation can surpass or go beyond the visual (or sensory) experience from which it derives. From a strictly empiricist standpoint what is not sensed cannot be represented; except as a combination of things that have been experienced. But perceptual experience is always limited by our view of the world and the properties of our visual system. It is therefore not surprising when human representation is found to be highly dependent on the initial viewpoint of the observer and on any shortcomings thereof. However, representation is not a static entity; it evolves with experience. The debate as to whether human representation of objects is view-dependent or view-invariant that has dominated research journals recently may simply be a discussion concerning how much information is available in the retinal image during experimental tests and whether this information is sufficient for the task at hand. Here we review an approach to the study of the development of human spatial representation under realistic problem solving scenarios. This is facilitated by the use of realistic virtual environments, exploratory learning and redundancy in visual detail. PMID- 11198238 TI - Reconstructing mental object representations: a machine vision approach to human visual recognition. AB - This paper introduces a new approach to assess visual representations underlying the recognition of objects. Human performance is modeled by CLARET, a machine learning and matching system, based on inductive logic programming and graph matching principles. The model is applied to data of a learning experiment addressing the role of prior experience in the ontogenesis of mental object representations. Prior experience was varied in terms of sensory modality, i.e. visual versus haptic versus visuohaptic. The analysis revealed distinct differences between the representational formats used by subjects with haptic versus those with no prior object experience. These differences suggest that prior haptic exploration stimulates the evolution of object representations which are characterized by an increased differentiation between attribute values and a pronounced structural encoding. PMID- 11198239 TI - Learning in brains and machines. AB - The problem of learning is arguably at the very core of the problem of intelligence, both biological and artificial. In this paper we sketch some of our work over the last ten years in the area of supervised learning, focusing on three interlinked directions of research: theory, engineering applications (that is, making intelligent software) and neuroscience (that is, understanding the brain's mechanisms of learning). PMID- 11198240 TI - Learning to recognize objects. AB - Several aspects of systems for learning pattern or object recognition rules are discussed. First, how are recognition rules developed and to what extent is structural pattern information embedded into these recognition rules. Second, how are these rules applied to the recognition of complex patterns such as objects embedded in scenes and how is evidence from different rules combined into a single evidence vector. Third, how can learned rules be improved through performance evaluation and feedback to rule generation stages. PMID- 11198241 TI - Learning paradigms for image interpretation. AB - In this paper we discuss image understanding and object recognition as a class of processes which involve binding what is seen with what is known. It follows from this perspective that it is important to explicate how systems may learn about spatial information from images, how it is encoded, and, how, in turn, such knowledge is matched with new image data. As well as discussing very specific solutions to these problems, this paper questions the view that our scientific understanding of image understanding is sufficiently circumscribed by the study of how image features are extracted and matched, per se. PMID- 11198242 TI - Learning about dynamic scenes. PMID- 11198243 TI - Spatio-temporal organization of behavior. AB - One of the most widely used terms in the study of human performance is attention. Yet it can also be argued that it is one of the most confusing and misunderstood. Huge variations in performance, from not noticing large changes in images or natural situations, to differences of tens of milliseconds have all been described as attentional effects. We argue that the large disparity in results can be more easily understood in the context of a fairly complete model of human performance that describes the execution of a set of complex natural tasks via a collection of visual routines that extract crucial information from the optical array. The description of visual routines is hierarchical. At the most abstract level, a scheduler must pick a small set of programs for the current tasks. Each program contains steps which are keyed to information in the scene. This is extracted by visual routines which run during a single fixation and extract pertinent information. The library of routines themselves are designed to execute quickly, but their actual performance depends on signal-to-noise characteristics of the imaged scene. The hierarchical description of behavior shows that questions about attention make sense in the context of the descriptive level in which they are embedded. We illustrate these principles with examples of driving behaviors. PMID- 11198244 TI - Graph matching for visual object recognition. PMID- 11198245 TI - Antioxidant supplements to prevent heart disease. Real hope or empty hype? AB - Antioxidants in foods and supplements are being widely promoted for their health benefits. Protection from heart disease is one claim that seems compelling in light of scientific evidence and large-scale observational studies. But will antioxidant supplements help your patients? To examine this question, Dr Tran reviews numerous clinical studies and evaluates the discrepancies between observational and clinical results. PMID- 11198246 TI - Superficial fungal infection of the skin. Where and how it appears help determine therapy. AB - Superficial fungal infections of the skin are a common presentation in clinical practice. Any skin surface, the mucous membranes, nail plates, and nail beds can be affected. Tinea pedis is the most common fungal infection and may affect up to 70% of the adult population worldwide. Ubiquitous candidal organisms are found in the oral flora of many healthy persons and result in infection in the presence of certain host factors or immunodeficiency disorders. Onychomycosis has had an increasing incidence worldwide, and it now accounts for almost half of all nail disorders. These and many other infections can have varying presentations as well as features that resemble nonfungal disorders. Therefore, it is important that primary care physicians are familiar with the many cutaneous fungal infections and their differential diagnosis to ensure that appropriate therapy is selected. PMID- 11198247 TI - Human error in perspective. The patient safety movement. PMID- 11198248 TI - An unusual vertebral radiographic finding. "H-type" vertebral deformity due to sickle cell disease. PMID- 11198249 TI - Abnormal uterine bleeding. Diagnostic considerations, management options. AB - The approach to diagnosis of abnormal uterine bleeding is guided by a sound knowledge of menstrual physiology and differential diagnosis. Often, simple anovulation is the underlying problem, although the possibility of pregnancy, endometrial hyperplasia with atypia, or benign reproductive tract disease must be considered. In the majority of cases, abnormal uterine bleeding can be fully evaluated and effectively treated medically without the need for gynecologic referral. PMID- 11198250 TI - Basics of joint injection. General techniques and tips for safe, effective use. AB - Successful joint and soft-tissue aspiration and injection rely on the physician's understanding of the indications, contraindications, and general techniques involved in these procedures. The procedures are generally well tolerated and can be used to treat many painful musculoskeletal and soft-tissue conditions. PMID- 11198251 TI - OTC agents for ringworm? PMID- 11198252 TI - Recognizing UTIs in infants and children. Early treatment prevents permanent damage. AB - The risk of irreversible renal scarring leading to hypertension and renal failure underscores the importance of expedient and accurate diagnoses of UTIs in infants and children. The selective use of invasive techniques to obtain urine for culture may reduce false-positive results that lead to unnecessary treatment. Subsequent management of UTIs depends on the age of the patient and the severity of the illness. Heightened awareness and prompt management of UTIs in infants and children can result in reduced morbidity and improved outcomes. PMID- 11198253 TI - Are water supplies safe from bioterrorism? PMID- 11198254 TI - Breast self-examination. PMID- 11198255 TI - Put a scanner in your pocket. Handheld OCR technology saves time and typing. PMID- 11198256 TI - The persistent nonhealing ulcer. Could it be basal cell carcinoma? PMID- 11198257 TI - Migraine's impact today. Burden of illness, patterns of care. AB - Migraine is a common disorder that causes severe headaches and associated nausea, photophobia, phonophobia, and temporary disability. Though the pain and other symptoms of migraine can be effectively managed, the condition remains underdiagnosed and undertreated. In this article, Drs Lipton, Stewart, Reed, and Diamond consider the scope and distribution of the migraine problem and the current patterns of care in the United States. PMID- 11198258 TI - A fresh look at migraine therapy. New treatments promise improved management. AB - Successful management of migraine headaches involves identifying and avoiding headache triggers and using appropriate abortive therapy once a headache is recognized. Pain relief measures include over-the-counter analgesics, parenteral NSAID therapy when needed, and use of antiemetics and cold packs. Narcotic analgesics are best used only as a "last resort" measure. Prophylactic therapy should be considered for patients who have more than two acute migraine attacks each month or whose daily activities are seriously compromised by headaches. For the patient in whom status migrainosus threatens well-being, hospitalization and more intensive therapy may be needed. PMID- 11198259 TI - Relief of cluster headache and cranial neuralgias. Promising prophylactic and symptomatic treatments. AB - When a patient presents with persistently unilateral head or face pain, cluster headache and trigeminal neuralgia should be considered. Diagnosis is based on the patient's history; anatomical studies are performed only to rule out problems other than tumor or stroke. A patient who presents with pain in the pharynx, tonsils, and ear--particularly if it is initiated by swallowing, yawning, or eating--may have glossopharyngeal neuralgia. Treatment with carbamazepine is indicated; if the patient does not respond to this drug, the diagnosis is doubtful. Several effective treatments are available for these conditions. Oxygen, drug therapy, or surgery may be indicated depending on the course of the disease. PMID- 11198260 TI - Sexual aspects of headache. How sexual function relates to headaches and their causes and treatment. AB - Since the sexual revolution of the 1960s, medical complications of sexual activity and sexual side effects related to use of medications have become a significant part of healthcare practice. Specifically, there has been an expanding interest in the treatment of headaches and their relationship to sexual function. Most sexual side effects associated with headache treatment are benign and can be managed with reassurance or changes in medication regimens. However, sudden headache should always be investigated carefully to rule out a dangerous intracranial event. PMID- 11198261 TI - Resources on headache. PMID- 11198262 TI - Prophylactic and symptomatic treatment of influenza. Current and developing options. AB - The influenza vaccine is the primary method for the prevention and control of influenza. Anti-influenza drugs also have been shown to be useful prophylactically and to shorten the duration of illness by 1 or 2 days when started within 48 hours of symptom onset. In this article, Dr Mossad discusses indications for the vaccine and compares the relative advantages and disadvantages of each of the anti-influenza drugs. PMID- 11198263 TI - Collecting cancer risk factor data from hospital outpatients: use of touch-screen computers. AB - The aim of this study was to assess the prevalence of selected cancer risk factor data from hospital outpatients and the proportion of "at risk" patients who would like help from hospital staff to reduce risk factors. A touch-screen computer collected data from outpatients in Newcastle, NSW, Australia. Eight hundred and nineteen outpatients completed the computerized interview. Of these, 35% were smokers, of whom 25% said that they would like help to stop smoking; 47% were overweight, with 48% indicating that they wanted assistance; 17% consumed harmful levels of alcohol, with 2% wanting help; 30% of eligible women were overdue for a Pap test, of whom 75% said that they wanted a referral to be screened, and 25% were overdue for a mammogram, of whom 83% said that they would like a referral for an examination. Touch-screen computerized health risk assessments are practical for collecting and monitoring valid cancer risk factor data for hospital outpatients. PMID- 11198264 TI - New evidence for antioxidant properties of vitamin C. AB - This study was designed to examine the effect of 500 to 5,000 mg of ascorbic acid on DNA adducts, natural killer (NK) cell activity, programmed cell death, and cell cycle analysis of human peripheral blood leukocytes. According to our hypothesis, if ascorbic acid is a pro-oxidant, doses between 500 and 5,000 mg should enhance DNA adduct formation, decrease immune function, change the cell cycle progression, and increase the rate of apoptosis. Twenty healthy volunteers were divided into four groups and given either placebo or daily doses of 500, 1,000 or 5,000 mg of ascorbic acid for a period of 2 weeks. On days 0, 1, 7, 15, and 21, blood was drawn from them, and the leukocytes were separated and examined for intracellular levels of ascorbic acid, the level of 8-hydroxyguanosine, NK cell activity, cell cycle progression, and apoptosis. Depending on the subjects, between a 0% and a 40% increase in cellular absorption of ascorbic acid was observed when daily doses of 500 mg were used. At doses greater than 500 mg, this cellular absorption was not increased further, and all doses produced equivalent increases in ascorbic acid on days 1 to 15. This increase in cellular concentration of ascorbic acid resulted in no statistically meaningful changes in the level of 8-hydroxyguanosine, increased NK cytotoxic activity, a reduced percentage of cells undergoing apoptosis, and switched cell cycle phases from S and G2/M to G0/G1. After a period of 1 week, with no placebo or vitamin washout, ascorbic acid levels along with functional assays returned to the baseline and became equivalent to placebos. In comparison with baseline values, no change (not more than daily assays variation) was seen in ascorbate concentrations or other assays during oral placebo treatment. We concluded that ascorbic acid is an antioxidant and that doses up to 5,000 mg neither induce mutagenic lesions nor have negative effects on NK cell activity, apoptosis, or cell cycle. PMID- 11198265 TI - Thyroperoxidase: a tumor marker for post-therapeutic follow-up of differentiated thyroid carcinomas? Results of a time course study. AB - Serum thyroperoxidase (TPO) and serum human thyroglobulin (hTg) were studied in 80 patients with differentiated thyroid carcinoma after thyroidectomy before and after the first therapeutic radioiodine application ("radioiodine thyroid ablation") and, in some cases, after the second radioiodine application. Eighteen patients with an autonomous adenoma were studied in the same manner. The values of TPO and hTg in 25 persons without thyroid impairment were used as controls. In 34 of 50 evaluable cases, TPO levels behaved as hTg during follow-up studies: The majority (n= 30) of these patients showed an increase in TPO and hTg serum levels immediately after radioiodine therapy, followed by a decrease approximately 3 days later. However, in 16 of 50 patients, the TPO and hTg serum levels showed different patterns of change both before and after radioiodine therapy. In six of seven patients with extensive postoperative residues and high anti-hTg levels, distinctly elevated TPO values were associated only by slightly elevated thyroglobulin values. There was no rise of TPO in autonomous adenoma except in patients treated with thyroid depressants. We assumed that TPO levels could serve as an "indicator" for destruction of thyroid cells or thyroid carcinoma cells and an aid in screening cases of false-negative hTg values. PMID- 11198266 TI - Quantitative detection of tumor M2-pyruvate kinase in plasma of patients with lung cancer in comparison to other lung diseases. AB - Lung cancer is one of the predominant causes of cancer death. The aim of this project is the development of a screening method in persons with high risk for developing lung cancer, based on the measurement of Tumor M2-pyruvate kinase (Tumor M2-PK). Tumor M2-PK is quantitatively detectable in ethylenediaminetetraacetic acid-plasma with a sensitive enzyme-linked immunosorbent assay. So far, 60 patients with newly diagnosed lung cancer were included. These were compared to 24 patients with acute inflammatory lung diseases, 56 patients with pneumoconiosis, 22 patients with obstructive airway diseases, and 28 healthy persons. Tumor patients and some individuals suffering from severe inflammatory lung diseases had significantly higher Tumor M2-PK concentrations in ethylenediaminetetraacetic acid-plasma than all the other groups. The histologic tumor type had no influence on the plasma levels of Tumor M2-PK. Tumor M2-PK concentrations correlate strongly with the tumor stage, showing significantly increasing concentrations with progressive tumor stages. The present data indicate that Tumor M2-PK could be a valuable tumor marker for the detection of lung cancer. PMID- 11198267 TI - Expression of bcl-2, bax-xL, and bcl-xS in endometrial and cervical tissues. AB - We assessed the protein expression levels of bcl-2, bax, bcl-xL, and bcl-xS in a group of 51 endometrial cancers and 8 normal samples as well as in 59 cervical neoplasms and in 15 normal cervical tissues. Neoplastic endometria (median, 1.30 absorbance units [AU]; range, 0.13-7.26 AU) had slightly higher bcl-2 levels than did normal tissue (median, 0.83 AU; range, 0.29-1.90 AU; P < .068), whereas bcl-2 was lower in neoplastic (median, 3.59 AU; range, 0.13-19.86 AU) than in normal cervical samples (median, 8.45 AU; range, 2.09-15.04 AU; P < .010). Bcl-xL levels were higher in endometrial carcinoma (median, 1.23 AU; range, 0.03(4.29 AU) than in normal tissues (median, 0.56 AU; range, 0.46-1.48 AU; P < .048), whereas no significant difference was observed in cervical tissues. Bax levels did not show any variation in either system. The protein bcl-xS was marginally detectable in only a few samples. In endometrial carcinoma, bcl-2 and bcl-xL levels were correlated inversely (r = -0.27; P < .054), whereas in cervical cancer, they were correlated directly (r = +0.40; P < .002). The different expression patterns of bcl-2 family members in endometrial and cervical tissues confirm the hypothesis of a strictly tissue-specific regulation of these proteins. PMID- 11198268 TI - Blood polyamine levels after oral ornithine load, a diagnostic marker of hyperproliferative premalignant and malignant stages in a model of colon carcinogenesis. AB - This study was performed to determine whether a single oral dose of ornithine (Orn), the substrate of ornithine decarboxylase (ODC), increases blood concentrations of polyamines premalignant stage, and whether blood polyamine levels could be used as predictive markers of cancer development. Male Wistar rats were divided into two groups, control and 1,2-dimethylhydrazine (DMH) treated rats. DMH (20 mg/kg body weight) was injected intraperitoneally once weekly for 10 weeks. Five, 7, and 10 weeks after the last injection when premalignant aberrant crypt foci have developed in the colon, blood levels of putrescine (PUT), spermidine (SPD), and spermine (SPM) were estimated before and after an oral load of ORN. The results showed that after a single oral load of Orn, blood PUT, but not SPD and SPM, concentrations were significantly higher in DMH-treated rats compared with control rats, indicating enhancement of ODC activity. These results support the view that the increased blood concentration of PUT after administration of Orn may be a useful marker to detect hyperproliferative premalignant and malignant stages of cancer development. PMID- 11198269 TI - Breast cancer screening among Cambodian American women. AB - Our aim was to describe and identify factors associated with breast cancer screening among Cambodian American women. We conducted a cross-sectional survey of 1,365 households using bilingual and bicultural interviewers. We found that low proportions of Cambodian American women were up to date on their clinical breast examinations (CBE; 42%) and mammograms (40%). More than 80% of women with female physicians have had at least one prior screening, and 52% have had the tests recently. Women with male Asian American physicians were less likely to have had screening as compared to women with female non-Asian physicians: ever had CBE (odds ratio [OR], 0.26); recent CBE (OR, 0.39); ever had mammogram (OR, 0.36); and recent mammogram (OR, 0.22). Breast cancer screening among Cambodian American women lags behind the general U.S. population. Tailored promotion efforts should address barriers and promote cancer screening by physicians, staff, and organizations serving this population. PMID- 11198270 TI - Ethnic differences in serum pepsinogen levels among Japanese and non-Japanese Brazilian gastric cancer patients and controls. AB - A low level of serum pepsinogen I (Pg I) is a risk factor for gastric cancer (GC); low levels of Pg I and the pepsinogen ratio (Pg I:Pg II) are correlated with chronic atrophic gastritis. We report serum Pg levels and compare the degree of association with GC among Japanese and non-Japanese Brazilians. Sera were cross-sectionally ascertained from 93 Japanese Brazilian patients category matched by age and sex with 110 controls, and 228 non-Japanese Brazilian patients individually matched by age and sex with one control. Among non-Japanese Brazilians, GC was associated with a Pg I level <30 ng/ml (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.7-3.8) and a Pg I:Pg II ratio < 3.0 (OR, 3.4; 95% CI, 2.2-5.3). However, among Japanese Brazilians, the association was present with a level of Pg I < 30 ng/ml (OR, 3.5; 95% CI, 1.9-6.3), and was weak with a Pg I:Pg II ratio < 3.0 (OR, 1.3; 95% CI, 0.73-2.4). Serum Pg I may be preferred to the Pg I:Pg II ratio to study the association between Pg and GC among Japanese Brazilians. PMID- 11198271 TI - Immunohistochemical localization of pancreatic secretory trypsin inhibitor in malignant pancreatic endocrine tumors. AB - Differentiation of benign from malignant pancreatic endocrine tumors by existing clinical, biochemical, histologic, and cytologic criteria is difficult. We immunohistochemically localized pancreatic secretory trypsin inhibitor (PSTI) in 28 pancreatic endocrine tumors (13 benign, 15 malignant). PSTI-immunoreactive cells were detected in nine endocrine tumors. Immunoreactivity in these tumors was detected in nearly all tumor cells in five cases, scattered cells in two cases, and a few cells in two cases. All positive cases were malignant, and eight were equal to or larger than 10 cm. Serum concentrations of PSTI were markedly elevated in the two patients so tested. PSTI may be a specific immunohistochemical marker for malignant pancreatic endocrine tumors. PMID- 11198273 TI - Cancer screening behaviors among Korean-American women. AB - The goals of this study were to evaluate breast and cervical cancer screening tests and to examine the correlates of cancer screening behaviors. A cross sectional face-to-face survey of 438 Korean-American women residing in Maryland was conducted. About 50% of women age 18 and older had had a Pap smear and 46.6% of these women age 40 and older had had a mammogram in the past 2 years. In multiple logistic regression analyses, the strongest correlate of screening behaviors was having a regular medical checkup. Age and acculturation were found to be important correlates of cancer screening tests: Women less than 50 years of age were more likely to have cancer screening tests than those 50 years and older. English language proficiency was associated with having a mammogram and the proportion of life spent in the United States was associated with having a Pap smear. Employment interacted with marital status for a Pap smear, with those married and unemployed being less likely to have a Pap smear than women who were both married and employed. For strategies to increase cancer-screening tests among Korean-American women, we need to aim at developing culturally appropriate educational programs about cancer for less acculturated and recent immigrants. PMID- 11198272 TI - Detection of prostate-specific membrane antigen expressing cells in blood obtained from renal cancer patients: a potential biomarker of vascular invasion. AB - Originally, prostate-specific membrane antigen (PSMA) was described in benign and malignant prostate cells. On the basis of recent reports that this antigen also is expressed in normal renal proximal tubular cells and in the neovascular endothelium associated with renal carcinoma, we used a nested reverse transcriptase-polymerase chain reaction assay to evaluate whether PSMA-expressing cells might be present in specimens of peripheral blood obtained from renal cancer patients, benign renal tumor patients, and healthy volunteers. Our reverse transcriptase-polymerase chain reaction PSMA assay had a sensitivity of detecting 1 lymph node prostate cancer (LNCaP) per 10(7) lymphocytes. None of the 20 non renal cancer controls were positive for PSMA mRNA, whereas 11 of 50 patients (22%) with diagnosed renal cancer were positive. Despite a comparative increase of PSMA positivity with stage, no statistical correlation was found. However, 44% of PSMA-positive patients had tumor size greater than 12 cm, versus only 9% in patients negative for PSMA (P = .03), and 67% of positive PSMA patients were found to have vascular invasion versus only 16% of patients negative for PSMA (P = .006; odds ratio, 10.8). This preliminary study suggests the possibility that PSMA expression in peripheral blood might be a useful biomarker for detecting or monitoring the progression of renal cancer in patients. PMID- 11198274 TI - Fine needle aspiration of bone tumors. AB - Fine needle aspiration cytology (FNAC) was performed in 226 cases of bone tumors and the cytohistologic correlation was calculated to assess the technique's diagnostic efficacy aided by immunocytochemistry, considering histopathology as the gold standard. Of the 226 cases, 136 were malignant and 72 cases were benign tumors. In the remaining 18 cases, cytohistopathologic examination revealed no bony lesion. There were 178 evaluable cases, but the specific morphologic diagnosis on FNAC was possible only in 159 cases with one false positive and 29 false negatives. Giant cell tumor (32%) and Ewing's sarcoma (22%) were the most common bony tumors encountered in this series. The diagnostic indices were calculated by a decision matrix comparison. The overall sensitivity and specificity were 86.0 (confidence interval [CI], 80.3-90.3) and 94.7 (CI, 71.9 99.7), respectively. The positive predictive value (PPV) was as high as 99.4 (CI, 96.5-100), while the negative predictive value (NPV) was 38.3 (CI, 24.9-53.6) with positive and negative likelihood ratios of 16.338 and 0.147, respectively. Diagnosis of malignant tumors was more accurate with a PPV of 99.2 (CI, 94.8 100.0) and specificity of 94.7 (CI, 71.9-99.7), while the sensitivity was 89.0 (CI, 82.2-93.5) and NPV was 54.5 (CI, 36.6-71.5). This study highlights the usefulness of FNAC along with the use of immunocytochemistry in the rapid diagnosis of bone tumors. PMID- 11198275 TI - Iontophoresis treatment of basal cell carcinoma with cisplatin: a case report. AB - Iontophoresis is a process that uses electrical current to increase the flux of ionized substances through tissue. Iontophoresis has been used in rehabilitation to decrease inflammation and pain using dexamethasone and lidocaine. In 1993, Chang et al. reported visual improvements in the lesions of nine patients diagnosed with basal cell carcinoma (BCC) following iontophoresis of cisplatin. The present case report describes the successful treatment of a 67-year-old male with a histologically confirmed BCC on his upper anterolateral left leg. The treatment consisted of four cycles of five successive days of cisplatin iontophoresis, with a 2-week rest period between cycles. The cisplatin solution (5 mL at 1 mg/mL) was used in combination with epinephrine hydrochloride. The effectiveness of the treatment was confirmed by post-treatment biopsies, which revealed granulation tissue scarring without evidence of BCC. Measurements of cellular proliferation were monitored immunohistochemically with Ki-67 and cell cycle distribution analyzed by flow cytometry. PMID- 11198276 TI - Deletion mapping on the short arm of chromosome 1 in Merkel cell carcinoma. AB - Twenty-two Merkel cell carcinoma (MCC) biopsies and six cell lines from 24 patients were examined for loss of heterozygosity (LOH) at 11 loci on 1p and one on 1q, to determine LOH regions on chromosome 1p. Sixteen (73%) tumors had LOH for at least one locus; 14 demonstrated LOH at more than one locus, and 7 (29%) samples had more than one region of loss, with 4 of these having loss at all informative loci on 1p. Three common regions of loss (SRO) were defined by LOH in multiple tumors. Eight samples demonstrated LOH between D1S214 and D1S160 (1p36), seven between D1S234 and D1S186 (1p35), and 11 for the region centromeric of D1S211 and D1S220 (1p32-1p33). Seven samples (29%) demonstrated more than one region of loss. LOH on 1p occurs frequently in MCC and more than one tumor suppressor gene on 1p is likely to play a role in the development of this tumor type. PMID- 11198277 TI - Herpes simplex virus type 1 (HSV-1)--induced retinitis following herpes simplex encephalitis: indications for brain-to-eye transmission of HSV-1. AB - Herpes simplex encephalitis is a severe neurological disease with high mortality and morbidity rates. Reactivated herpes simplex virus type 1 (HSV-1) can cause relapses and might even spread to the retina, where it can induce a potentially blinding eye disease, known as acute retinal necrosis. In the present study, the HSV-1 strains in the brain and eye of 2 patients with acute retinal necrosis following an episode of herpes simplex encephalitis were genotyped. The HSV-1 strains in both the brain and eye were identical in each patient, but they differed interindividually. The data suggest brain-to-eye transmission of HSV-1 in these patients. PMID- 11198278 TI - A novel mtDNA mutation in the ND5 subunit of complex I in two MELAS patients. AB - We identified a novel heteroplasmic mutation in the mitochodrial DNA gene encoding the ND5 subunit of complex I. This mutation (13514A-->G) hits the same codon affected by a previously reported mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS)-associated mutation (13513G-->A), but the amino acid replacement is different (D393G vs D393N). The 13514A-->G mutation was found in two unrelated MELAS-like patients. However, in contrast to typical MELAS, lactic acidosis was absent or mild and the muscle biopsy was morphologically normal. Strongly positive correlation between the percentage of heteroplasmy and defective activity of complex I was found in cybrids. We found an additional 13513G-->A-positive case, affected by a progressive mitochondrial encephalomyopathy. Our results clearly demonstrate that the amino acid position D393 is crucial for the function of complex I. Search for D393 mutations should be part of the routine screening for mitochondrial disorders. PMID- 11198279 TI - Decreased binding of [11C]flumazenil in Angelman syndrome patients with GABA(A) receptor beta3 subunit deletions. AB - We used positron emission tomography (PET) to study brain [11C]flumazenil (FMZ) binding in four Angelman syndrome (AS) patients. Patients 1 to 3 had a maternal deletion of 15q11-q13 leading to the loss of beta3 subunit of gamma-aminobutyric acidA/benzodiazepine (GABA(A)/BZ) receptor, whereas Patient 4 had a mutation in the ubiquitin protein ligase (UBE3A) saving the beta3 subunit gene. [11C]FMZ binding potential in the frontal, parietal, hippocampal, and cerebellar regions was significantly lower in Patients 1 to 3 than in Patient 4. We propose that the 15q11-q13 deletion leads to a reduced number of GABA(A)/BZ receptors, which could partly explain the neurological deficits of the AS patients. PMID- 11198280 TI - No evidence for genetic association or linkage of the cathepsin D (CTSD) exon 2 polymorphism and Alzheimer disease. AB - Two recent case-control studies have suggested a strong association of a missense polymorphism in exon 2 of the cathepsin D gene (CTSD) and Alzheimer disease (AD). However, these findings were not confirmed in another independent study. We analyzed this polymorphism in two large and independent AD study populations and did not detect an association between CTSD and AD. The first sample was family based and included 436 subjects from 134 sibships discordant for AD that were analyzed using the sibship disequilibrium test (SDT, p = 0.68) and the sib transmission/disequilibrium test (Sib-TDT, p = 0.81). The second sample of 200 AD cases and 182 cognitively normal controls also failed to show significant differences in the allele or genotype distribution in cases versus controls (chi2, p = 0.91 and p = 0.88, respectively). In addition, two-point linkage analyses in an enlarged family sample (n = 670) did not show evidence for linkage of the chromosomal region around CTSD. Thus, our analyses on more than 800 subjects suggest that if an association between the CTSD exon 2 polymorphism and AD exists, it is likely to be smaller than previously reported. PMID- 11198281 TI - SCA12 is a rare locus for autosomal dominant cerebellar ataxia: a study of an Indian family. AB - Spinocerebellar ataxia 12 (SCA12) is an autosomal dominant cerebellar ataxia (ADCA) described in a single family with a CAG repeat expansion in the PPP2R2B gene. We screened 247 index cases, including 145 families with ADCA, for this expansion. An expanded repeat ranging from 55 to 61 triplets was detected in 6 affected and 3 unaffected individuals at risk in a single family from India. The association of the PPP2R2B CAG repeat expansion with disease in this new family provides additional evidence that the mutation is causative. PMID- 11198282 TI - Inherited Myoclonus-dystonia syndrome: narrowing the 7q21-q31 locus in German families. AB - Genetic studies were performed in four German families with autosomal dominant myodonus-dystonia syndrome. Mutations in the D2 dopamine receptor gene, which have been implicated in this disorder, were excluded in all four families by linkage analysis and direct sequencing. All four families supported linkage to the second reported locus on chromosome 7q21 with a combined maximum multipoint lod score of 5.99. The observation of key recombinations in one family refined the disease locus to a 7.2 cM region flanked by the markers D7S652 and D7S2480. PMID- 11198283 TI - Variable phenotype of Alzheimer's disease with spastic paraparesis. AB - A variant form of Alzheimer's disease (AD), in which spastic paraparesis (SP) precedes dementia, is characterised by large, noncored, weakly neuritic Abeta amyloid plaques resembling cotton wool balls and is caused by genomic deletion of presenilin 1 exon 9. A pedigree with a 5.9 kb exon 9 deletion shows a phenotypic spectrum including subjects with typical AD or with SP and numerous cotton wool plaques. In SP subjects, dementia onset is delayed and modified. This phenotypic variation suggests that modifying factors are associated with exon 9 deletions. PMID- 11198284 TI - Distal anterior compartment myopathy: a dysferlin mutation causing a new muscular dystrophy phenotype. AB - We report a family with a new phenotype of autosomal recessive muscle dystrophy caused by a dysferlin mutation. The onset of the illness is distal, in the muscles of the anterior compartment group. The disease is rapidly progressive, leading to severe proximal weakness. Muscle biopsy showed moderate dystrophic changes with no vacuoles. Dysferlin immunostaining was negative. Gene analysis revealed a frameshift mutation in the exon 50 (delG5966) of the DYSF gene. This phenotype further demonstrates the clinical heterogeneity of the dysferlinopathies. PMID- 11198285 TI - Chlamydia pneumoniae-specific humoral immune responses and clinical disease parameters in multiple sclerosis. PMID- 11198286 TI - Tracking post-stroke recovery with magnetoencephalography. PMID- 11198287 TI - Hypocretin deficiency in familial symptomatic narcolepsy. PMID- 11198288 TI - Down's syndrome fibroblasts anticipate the accumulation of specific ageing related mtDNA mutations. PMID- 11198289 TI - Decreased serum ceruloplasmin and copper levels in cervical dystonia. PMID- 11198290 TI - Prospects for the treatment of multiple sclerosis by raising serum levels of uric acid, a scavenger of peroxynitrite. PMID- 11198291 TI - Widespread occurrence of intranuclear atrophin-1 accumulation in the central nervous system neurons of patients with dentatorubral-pallidoluysian atrophy. AB - Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion. In the present study of DRPLA, we have demonstrated immunohistochemically that diffuse accumulation of mutant atrophin-1 in the neuronal nuclei, rather than the formation of neuronal intranuclear inclusions (NIIs), was the predominant pathologic condition and involved a wide range of central nervous system regions far beyond the systems previously reported to be affected. In the neuronal nuclei harboring NIIs, promyelocytic leukemia protein (PML) nuclear bodies were redistributed into a single NII, and the CREB (cAMP-responsive element-binding protein)-binding protein was also recruited into NIIs. The results suggest that the novel lesion distribution revealed by the diffuse nuclear labeling may be responsible for a variety of clinical features, such as dementia and epilepsy in DRPLA, and that certain transcriptional abnormalities may be induced secondarily in neuronal nuclei with the formation of NIIs. PMID- 11198292 TI - Ocular oscillations induced by shifts of the direction and depth of visual fixation. AB - Shifts of the point of fixation between two targets aligned on one eye that are located near and far (Muller paradigm) stimulates a combined saccadic-vergence movement. In normal subjects, this test paradigm often induces saccadic oscillations of about 0.3 degrees at 20 to 30 Hz. We measured eye movements using the magnetic search coil technique in 2 patients recovering from viral opsoclonus myoclonus syndrome, comparing saccadic-vergence responses to the Muller paradigm with conjugate saccades between distant targets. Both patients exhibited intermittent conjugate ocular oscillations of about 4 to 5 degrees amplitude at about 10 Hz. Combined saccadic-vergence movements induced these oscillations twice as often as did conjugate saccades. One patient also exhibited disjunctive ocular oscillations at 10 Hz while sustaining fixation on the near target. The Muller paradigm provides a useful clinical and experimental technique for inducing saccadic oscillations. The probable mechanism is that pontine omnipause neurons, which normally gate saccades, are inhibited during the sustained vergence movement that follows the saccadic component of the response to the Muller paradigm. PMID- 11198293 TI - Quantitative neuropathological changes in presymptomatic Huntington's disease. AB - Morphometric studies of the tail of the caudate nucleus, the site where the pathology is first seen, were performed on 16 brain specimens collected from individuals at risk for inheriting Huntington's disease (HD). Medical records and information obtained from immediate family members indicated that all had died without symptoms of HD. Six individuals had 37 or more CAG repeats and were designated HD gene carriers, whereas 10 were determined to be non-carriers. Cell counts of the tail of the caudate nucleus revealed an increased density of oligodendrocytes among the presymptomatic HD gene carriers (mean cells/field: carriers = 40.0, noncarrier = 21.3; age, sex, repeated measure adjusted F[126] = 11.7, p = 0.0008). No statistically significant differences were found between HD carriers and noncarriers in the density of neurons (carriers = 16.9, noncarriers = 15.5), astrocytes (carriers = 27.8, noncarriers = 21.3) or microglial cells (carriers = 7.9, noncarriers = 5.6). Ubiquitin immunostaining performed in 3 gene carriers revealed intranuclear inclusions in all 3 cases, including 1, with 37 repeats, who died 3 decades before the expected age for onset of the clinical syndrome. Normal densities of other cell types and careful macroscopic examination suggest that the increase in oligodendroglial density is not a consequence of atrophy and may instead reflect a developmental effect of the HD gene. PMID- 11198294 TI - Sexual arousal and orgasm in women: effects of spinal cord injury. AB - Sexual disorders are common in women; however, the neurological basis of female sexual response has not been adequately investigated. This information is necessary to characterize the impact of various neurological disorders on sexual arousal in women and to develop appropriate management strategies for sexual dysfunction. To assess the spinal mediation of sexually stimulated genital vasocongestion in women, we conducted two laboratory-based, controlled analyses: (1) of women's genital, subjective, and autonomic responses to audiovisual erotic and audiovisual erotic combined with manual genital stimulation; and (2) of women's ability to achieve orgasm. Subjects included 68 premenopausal women with spinal cord injuries (SCIs) and 21 able-bodied, age-matched controls. Results indicated that preservation of sensory function in the T11-L2 dermatomes is associated with psychogenically mediated genital vasocongestion. Less than 50% of women with SCIs were able to achieve orgasm, compared with 100% of able-bodied women (p = 0.001). Only 17% of women with complete lower motor neuron dysfunction affecting the S2-S5 spinal segments were able to achieve orgasm, compared with 59% of women with other levels and degrees of SCIs (p = 0.048). Time to orgasm was significantly increased in women with SCIs compared with able-bodied controls (p = 0.049). Independent raters were unable to differentiate between subjective descriptions of orgasm from SCI women compared with controls. This information should be used when counseling women with spinal dysfunction about their sexual potential. PMID- 11198295 TI - Migraine, aura, and cortical spreading depression: why are we still talking about it? PMID- 11198296 TI - Causes of epilepsies: insights from discordant monozygous twins. AB - Whereas some patients with epilepsy have known acquired or genetic causes, in many the cause is unknown. By analyzing monozygotic twins, discordant for epilepsy, subtle etiological factors may be detected. We analyzed 12 monozygotic, discordant twins for factors explaining discordancy. These factors were presence of major clinical risk factors, presence of possibly epileptogenic lesions on brain magnetic resonance imaging (MRI), and quantitative brain volume abnormalities. Major risk factors, with associated acquired lesions were found in 4 of 12 twins. An MRI lesion without a major risk factor was found in a further 4 of 12 twins. Two of these had unilateral malformations of cortical development, 1 had bilateral periventricular heterotopia, and 1 had focal atrophy. Significant twin-twin differences in MRI volumes without obvious MRI lesions or major risk factors were found in 2 of 12 twins. Both had larger volumes than their co-twins, and idiopathic generalized epilepsy. No clinical or MRI findings accounting for discordance for epilepsy were found in 2 of 12 twins. In 10 of 12 pairs a clinical or MR correlate of epilepsy was found; some of those were subtle and only apparent by twin-twin comparison. They may be due to occult acquired factors, such as prenatal insults, or to genetic abnormalities resulting from postfertilization genetic processes. PMID- 11198297 TI - The selective vulnerability of brainstem nuclei to Alzheimer's disease. AB - In a study of thioflavin S-stained serial sections from the entire brainstem, we found that the inferior and superior colliculi and the autonomic, monoaminergic, cholinergic, and classical reticular nuclei were affected with varying degrees of severity and frequencies in 32 patients with Alzheimer's disease, whereas no changes were seen in the brainstems of 26 control subjects. The majority of the affected nuclei in patients with Alzheimer's disease exhibit either neurofibrillary tangles or senile plaques, and only a few display both. However, when sections were immunostained with the antibodies 10D5 and AT8 or ALZ50, both beta-amyloid and hyperphosphorylated epitopes of tau protein were found to be present in various concentrations in all the affected nuclei. Our findings suggest that each brainstem nucleus has a distinct vulnerability to Alzheimer's disease-related pathological changes. Given that each nucleus has idiosyncratic neuroanatomical connections and prevailing neurochemical characteristics, the heterogeneous collection of brainstem nuclei can be considered a suitable anatomical ground for further investigation of selective vulnerability in Alzheimer's disease. The finding of severe pathological changes in some brainstem nuclei also raises the possibility that the dysfunction of these nuclei may contribute to the cognitive defects and increased rates of morbidity and mortality in patients with Alzheimer's disease. PMID- 11198298 TI - Selective alterations in glutamate and GABA receptor subunit mRNA expression in dysplastic neurons and giant cells of cortical tubers. AB - The molecular pharmacologic basis of epileptogenesis in cortical tubers in the tuberous sclerosis complex is unknown. Altered transcription of genes encoding glutamatergic and gamma-aminobutyric acid (GABA)-ergic receptors and uptake sites may contribute to seizure initiation and may occur selectively in dysplastic neurons and giant cells. Arrays containing GABA A (GABAAR), GluR, NMDA receptor (NR) subunits, GAD65, the vesicular GABA transporter (VGAT), and the neuronal glutamate transporter (EAAC1) cDNAs were probed with amplified poly (A) mRNA from tubers or normal neocortex to identify changes in gene expression. Increased levels of EAAC1, and NR2B and 2D subunit mRNAs and diminished levels of GAD65, VGAT, GluR1, and GABAAR alpha1 and alpha2 were observed in tubers. Ligand-binding experiments in frozen tuber homogenates demonstrated an increase in functional NR2B-containing receptors. Arrays were then probed with poly (A) mRNA from single, microdissected dysplastic neurons, giant cells, or normal neurons (n = 30 each). Enhanced expression of GluR 3, 4, and 6 and NR2B and 2C subunit mRNAs was noted in the dysplastic neurons, whereas only the NR2D mRNA was upregulated in giant cells. GABAAR alpha1 and alpha2 mRNA levels were reduced in both dysplastic neurons and giant cells compared to control neurons. Differential expression of GluR, NR, and GABAAR mRNAs in tubers reflects cell-specific changes in gene transcription that argue for a distinct molecular phenotype of dysplastic neurons and giant cells and suggests that dysplastic neurons and giant cells make differential contributions to epileptogenesis in the tuberous sclerosis complex. PMID- 11198299 TI - Is there a correlation between spreading depression, neurogenic inflammation, and nociception that might cause migraine headache? AB - The time course of propagation of scotoma and blood flow changes during migraine aura parallels the phenomenon of cortical spreading depression (CSD). It was proposed that CSD generates a sterile neurogenic inflammation in the meninges, which may then lead to the activation or sensitization of nociceptors, thus generating headache. We performed rat experiments in which the effect of CSD on plasma extravasation in the dura mater and on neuronal activity in deep laminae of the trigeminal nucleus was assessed in vivo. CSD did not alter dural plasma extravasation measured by means of bovine serum albumin-coupled flourescein (n = 17 rats) compared to the CSD-free contralateral side. In an in vitro model, the application of KCl to the dura at concentrations extracellularly found during CSD did not alter the release of calcitonin gene-related peptide and prostaglandin E2 from the dura. In 33 rats, neither single CSDs nor a series of CSDs altered ongoing neuronal activity or mechanical and/or thermal sensitivity of the deeply located neurons to stimulation of their receptive fields in the dura mater. These results are at variance with data that showed increased c-Fos labeling in superficial laminae of the trigeminal nucleus following CSD. They do not suggest that CSD initiates migraine headache via neurogenic inflammation. PMID- 11198300 TI - Role of mitochondrial dysfunction and dopamine-dependent oxidative stress in amphetamine-induced toxicity. AB - To define the molecular mechanisms underlying amphetamine (AMPH) neurotoxicity, primary cultures of dopaminergic neurons were examined for drug-induced changes in dopamine (DA) distribution, oxidative stress, protein damage, and cell death. As in earlier studies, AMPH rapidly redistributed vesicular DA to the cytoplasm, where it underwent outward transport through the DA transporter. DA was concurrently oxidized to produce a threefold increase in free radicals, as measured by the redox-sensitive dye dihydroethidium. Intracellular DA depletion using the DA synthesis inhibitor alpha-methyl-p-tyrosine or the vesicular monoamine transport blocker reserpine prevented drug-induced free radical formation. Despite these AMPH-induced changes, neither protein oxidation nor cell death was observed until 1 and 4 days, respectively. AMPH also induced an early burst of free radicals in a CNS-derived dopaminergic cell line. However, AMPH mediated attenuation of ATP production and mitochondrial function was not observed in these cells until 48 to 72 hours. Thus, neither metabolic dysfunction nor loss of viability was a direct consequence of AMPH neurotoxicity. In contrast, when primary cultures of dopaminergic neurons were exposed to AMPH in the presence of subtoxic doses of the mitochondrial complex I inhibitor rotenone, cell death was dramatically increased, mimicking the effects of a known parkinsonism-inducing toxin. Thus, metabolic stress may predispose dopaminergic neurons to injury by free radical-promoting insults such as AMPH. PMID- 11198301 TI - Lack of activation of human secondary somatosensory cortex in Unverricht-Lundborg type of progressive myoclonus epilepsy. AB - Previous electroencephalographic and magnetoencephalographic studies have demonstrated giant early somatosensory cortical responses in patients with cortical myoclonus. We applied whole-scalp magnetoencephalography to study activation sequences of the somatosensory cortical network in 7 patients with Unverricht-Lundborg-type progressive myoclonus epilepsy diagnostically verified by DNA analysis. Responses to electric median nerve stimuli displayed 30-msec peaks at the contralateral primary somatosensory cortex that were four times stronger in patients than in control subjects. The amplitudes of 20-msec responses did not significantly differ between the groups. In contrast to control subjects, 5 patients displayed ipsilateral primary somatosensory cortex activity at 48 to 61 msec in response to both left- and right-sided median nerve stimuli. Furthermore, their secondary somatosensory cortex was not significantly activated. These abnormalities indicate altered responsiveness of the entire somatosensory cortical network outside the contralateral primary somatosensory cortex in patients with Unverricht-Lundborg-type progressive myoclonus epilepsy. The deficient activation of the secondary somatosensory cortex in Unverricht Lundborg patients may reflect disturbed sensorimotor integration, probably related to impaired movement coordination. PMID- 11198302 TI - Bruising and the ketogenic diet: evidence for diet-induced changes in platelet function. AB - Excessive bruising is a symptom noted by parents of some children treated with the ketogenic diet for epilepsy control, although this side effect is not reported in the literature. We evaluated our cohort of current and past diet treated patients for symptoms of bruising or bleeding through chart review and prospective screening at clinic follow-up visits. A significant increase in bruising or other minor bleeding was reported and/or observed in 16 of 51 patients (31.4%). There were no differences in sex distribution or number of anticonvulsants used between patients with bruising/bleeding and those without this symptom, although the group with bruising/bleeding was significantly younger. No specific anticonvulsant was associated with bruising/bleeding. Six patients with diet-induced bruising/bleeding underwent an investigation for bleeding diathesis. Five of these patients had prolonged bleeding times and all had diminished responsiveness to various platelet aggregating agents, with no evidence of a release defect. The abnormalities all normalized in the 1 patient tested after ceasing the diet. No patients had serious hemorrhage. One patient had mild von Willebrand disease, which had been asymptomatic before diet initiation. Some patients were Stimate responsive, suggesting a treatment for more severe bouts of symptoms. These data suggest that a ketogenic diet-related bleeding tendency occurs in about one third of treated patients owing to preexisting factors defining susceptibility in combination with diet-induced depression of platelet responsiveness, possibly related to changes in platelet membrane lipid composition and/or concentration and resultant effects on function of membrane-embedded proteins. Patients on the diet undergoing anticoagulation or surgery should be evaluated carefully for symptoms of bleeding tendency. PMID- 11198303 TI - Coronary-to-pulmonary fistulae: what are they? What are their causes? What are their functional consequences? PMID- 11198304 TI - Reflections from the past and thoughts for the future. PMID- 11198305 TI - Impact of the "stent-when-feasible" policy on in-hospital and 6-month success and complication rates after coronary angioplasty: single-center experience with 17,956 revascularization procedures (1993-1997). AB - This retrospective, observational, single-center study analyzed the results of a "stent-when-feasible" policy in a real-world setting. The study began in the "pre stent" period (1993) and ended after the beginning of the "routine stent" period (1997). When the 1993 and 1997 global data were compared, the early and 6-month results included significant improvements in the rates of angiographic success (89.3% vs 97.1%), emergency surgical revascularization (1.0% vs 0.3%), freedom from in-hospital major events (91.2% vs 95.9%), and freedom from 6-month major events (77.2% vs 85.1%). The 6-month redo revascularization rate was reduced by almost half for "any catheter intervention" (19.6% vs 10.7%) and was lowest after stent use (7.7% in 1997). PMID- 11198306 TI - The string phenomenon: an important cause of internal mammary artery graft failure. AB - Internal mammary arteries are the grafts of choice for coronary artery bypass because they are generally free of atherosclerosis and they have high patency rates as grafts. There are, however, increasing reports of graft failure due to diffuse or distal narrowing, known as the string phenomenon. From June 1999 to October 1999, we prospectively reviewed all cases of internal mammary artery angiography at our institution. Twenty-eight cases of internal mammary artery graft failure were identified (M:F, 15:13; mean age, 62 years) out of 261 patients who had undergone internal mammary artery grafting at any institution, including ours. The mean interval between coronary artery bypass and re angiography was 35 months. There was evidence of competitive flow in 81% (22 of 27) of patients whose internal mammary grafts had developed the string sign. This observational study supports the hypothesis that competitive flow predisposes internal mammary grafts to the string phenomenon. Given the high frequency of competitive flow situations amongst patients with internal mammary artery graft failure, caution should be exercised in the anastomosis of the internal mammary artery to recipient vessels that are less than severely stenosed. PMID- 11198307 TI - Should a regurgitant mitral valve be replaced simulataneously with a stenotic aortic valve? AB - Mitral valve regurgitation frequently accompanies aortic valve stenosis. It has been suggested that mitral regurgitation improves after aortic valve replacement alone and that the mitral valve need not be replaced simultaneously Furthermore, mitral regurgitation associated with coronary artery disease, particularly in patients with poor left ventricular function, shows immediate improvement after coronary artery bypass grafting. We studied 60 consecutive patients with aortic stenosis and mitral regurgitation to determine the degree of improvement in mitral regurgitation after aortic valve replacement alone versus aortic valve replacement combined with coronary artery bypass grafting. Thirty-six of the patients had normal coronary arteries (Group 1); the other 24 had symptomatic coronary artery disease requiring bypass surgery (Group 2). Echocardiography was performed preoperatively, 1 week postoperatively, and at follow-up. In Group 1, left ventricular ejection fraction did not improve early or at 2.5 months postoperatively, but mitral regurgitation improved gradually during follow-up. In Group 2, mitral regurgitation showed improvement 1 week postoperatively (p < 0.001), and left ventricular ejection fraction was improved at 2.5 months. We conclude that patients with aortic valve stenosis and mild-to-severe mitral regurgitation, without echocardiographic signs of chordal or papillary muscle rupture and without coronary artery disease, should undergo aortic valve replacement alone. The mitral regurgitation will remain the same or improve. For patients with coexisting coronary artery disease, simultaneous aortic valve replacement and coronary artery bypass grafting are imperative; however, the mitral valve again requires no intervention, since mitral regurgitation improves significantly after the other 2 procedures. PMID- 11198308 TI - Cardiac surgery in patients infected with human immunodeficiency virus. AB - From January 1991 through December 1999, 5 consecutive patients who were infected with human immunodeficiency virus presented in need of cardiac surgery. All were men; the median age was 44 years. Two of them presented with mitral and aortic infectious valve endocarditis, 1 with tricuspid endocarditis, 1 with prosthetic valve endocarditis, and 1 with pericarditis and pericardial tamponade. Under cardiopulmonary bypass, the 4 patients with endocarditis underwent these procedures: mitral and aortic valve replacement (2), tricuspid valve replacement (1), and aortic valve replacement (reoperation) and concomitant repair of a mycotic ascending aortic aneurysm (1). In the patient who had pericardial effusion, subxifoid pericardiostomy and drainage were performed, and a pericardial window was created. There was no intraoperative mortality. The patient with pericardial effusion died 8 days after surgery; he was in septic shock and had multiple organ failure. Two deaths occurred at 2 and 63 months, due to hemoptysis and sudden death, respectively. The 2 patients who underwent double valve replacement are alive and in good condition after a median follow-up of 71 months. Cardiac surgery is indicated in selected patients infected by the human immunodeficiency virus. These patients are frequently drug abusers or homosexual. Valvular endocarditis is the most common finding. Hospital morbidity and mortality rates are higher than usual in this group of patients. PMID- 11198309 TI - Assessment of perfusion toward the aortic valve using the new dispersion aortic cannula during coronary artery bypass surgery. AB - When there is an echocardiographic diagnosis of severe mobile atherosclerotic plaque in the aortic arch or descending aorta, perfusion toward the aortic arch during cardiopulmonary bypass may create a high risk of embolic neurologic injury. Other perfusion methods, such as cannulation of the femoral or axillary arteries, are not always possible, due to atherosclerosis. The ascending aorta may be an alternative site for perfusion, since it is less frequently diseased. We assessed a new technique of perfusion toward the aortic valve using a new cannula designed for this purpose (Dispersion aortic cannula). Our study included 100 consecutive patients, 72 men and 28 women, with an average age of 68 +/- 1.0 years (range, 39-89 years). There were no complications related to insertion of the cannula or perfusion. The ascending aorta could be cross-clamped and side clamped without perfusion problems. Three deaths occurred; none was related to the cannulation technique. No intra-operative stroke occurred. Two patients suffered neurologic events, one on day 1 and the other on day 6; both had been fully alert after surgery. Perfusion toward the aortic valve appears to be safe and hemodynamically effective. This cannulation technique appears to be an acceptable alternative to present methods. Comparative studies will be needed to determine whether this alternative technique is effective in patients with severe aortic arch disease. PMID- 11198310 TI - Bentall operation with valved homograft conduit. AB - Lesions of the ascending aorta associated with aortic valve disease are usually treated by implanting a prosthetic valved conduit (Bentall procedure). In this report, we present our experience in which a valved homograft conduit was used for the procedure. Six patients underwent a Bentall procedure with the use of a cryopreserved valved homograft conduit. Two of the patients had annuloaortic ectasia, 2 had Marfan syndrome, and 1 had an atherosclerotic aneurysm of the aorta. One patient had severe aortic stenosis due to a bicuspid aortic valve, along with an aneurysm and localized dissection of the ascending aorta. In all of the patients, the aortic annulus was substantially dilated, with accompanying moderate-to-severe aortic regurgitation. A standard procedure was performed with moderate hypothermia, cardiopulmonary bypass, and aortic and bicaval cannulation. The ascending aorta and the aortic valve were replaced with a cryopreserved valved homograft conduit (aortic in 5 patients and pulmonary in 1). The native coronary ostia were anastomosed directly to the homograft. Echocardiography, which was performed intraoperatively, before discharge from the hospital, and at follow-up visits (1 to 36 months), revealed good valve function without dilatation of the homograft conduits. There was 1 late death due to Aspergillus fumigatus endocarditis, 6 months postoperatively. In 1 patient, magnetic resonance imaging performed at 24 months revealed normal caliber of the homograft conduit. We conclude that the Bentall procedure can be performed, safely and with excellent results, using cryopreserved homograft conduits. PMID- 11198312 TI - Austin Flint: clinician, teacher, and visionary. PMID- 11198311 TI - Update on endovascular treatment of peripheral vascular disease: new tools, techniques, and indications. AB - The treatment of peripheral vascular disease is one of the most rapidly expanding fields of medicine today At one time, patients who had peripheral vascular disease had few medical or surgical options. Now, however, options abound. The number of peripheral interventions increased from 90,000 in 1994 to more than 200,000 in 1997 and endovascular techniques may soon replace up to 50% of traditional vascular operations. Cardiologists, interventional radiologists, and vascular surgeons bring various types of expertise to endovascular intervention; nonetheless, they seem to share similar levels of enthusiasm about this treatment option. The many advantages to the patient that such intervention offers over traditional surgery, such as the avoidance of anesthesia and other surgical risks, the rapid recovery time, and the relatively low treatment costs, provide encouragement to these specialists. Endovascular intervention requires dedication on the part of practitioners, because it demands such complete knowledge of vascular disease and of the anatomic changes experienced by the patient. The challenge is intensified by the continual introduction of new products and methods. We hope, herein, to offer pertinent information about recent advances in interventional techniques and devices, and to provide a framework for future education. PMID- 11198313 TI - Local pulmonary malformation caused by bilateral coronary artery and bronchial artery fistulae to the left pulmonary artery in a patient with coronary artery disease. AB - At 10 years of age and again at 25, our patient had been treated for pulmonary tuberculosis due to the presence of a localized pulmonary shadow. Coronary angiography at age 59 revealed 3 fistulous communications: from the right and circumflex coronary arteries and from the left bronchial artery. All 3 emptied into the same recipient artery, the distal part of a left pulmonary artery branch, which produced substantial left-to-right shunt. On computed tomography, cystic formations could be seen in the pulmonic area. The pulmonary tuberculosis for which this patient had been treated in his youth was in the same part of the lung where the shunt was discovered. Our conclusion is that the initial diagnosis was in error. PMID- 11198314 TI - Plexus between internal mammary graft and pulmonary vasculature after minimally invasive coronary surgery. AB - We report a complication associated with minimally invasive direct coronary artery bypass grafting surgery The patient suffered a nonfatal anterior myocardial infarction 1 day after he underwent minimally invasive bypass grafting using the internal mammary artery. Two months later, coronary arteriography revealed a fistulous connection between the left internal mammary graft and the left pulmonary vasculature. To our knowledge, this particular complication has not been reported following minimally invasive coronary surgery. PMID- 11198315 TI - Double aortic arch in D-transposition of the great arteries: confirmation of dominant arch by magnetic resonance imaging. AB - We report the case of a female infant who had the rare combination of double aortic arch and D-transposition of the great arteries. The double aortic arch was diagnosed at the time of her arterial switch procedure. Magnetic resonance imaging identified the left arch as dominant, and the right arch was successfully ligated. PMID- 11198316 TI - Right ventricular and septal anomalies complicated by subacute bacterial endocarditis. AB - We report the case of a 31-year-old woman with no history of heart disease. She came to the hospital with fever, dyspnea, palpitation, and edema of the lower extremities. She was found to have aortic, mitral, and pulmonary valve insufficiency, and the initial diagnosis was subacute bacterial endocarditis. At surgery, we replaced the aortic and mitral valves with mechanical prostheses and the pulmonary valve with a bioprosthesis. The prostheses were soaked intraoperatively with fluconazole and the heart chambers were irrigated with povidone-iodine to prevent infection by bacteria and fungi. We also found 2 previously unsuspected anomalies: 1 was a muscular bundle that divided the right ventricle into 2 chambers, and the other was a ventricular septal defect, 1.0 cm in diameter. We resected the muscular bundle and patched the septal defect. The patient had an uneventful postoperative course and was in New York Heart Association functional class I at the 15-month follow-up visit. We speculate that this patient's congenital anomalies made the heart more susceptible to damage from the endocarditis. Therefore, any patient who has infective endocarditis should also be examined closely for congenital defects. PMID- 11198317 TI - Tricuspid and pulmonary valve involvement in carcinoid disease. AB - We report the case of a 62-year-old woman in whom carcinoid disease had been diagnosed 6 years earlier. She subsequently developed tricuspid and pulmonary valve disease. Both valves were incompetent and mildly stenotic. The tricuspid valve required surgery; the pulmonary vaive was explored but not treated. Valve surgery in patients with carcinoid disease is discussed in light of the prognosis of these patients, the timing of valvular lesion presentation, and the choice of prosthesis. The justification for multiple-valve procedures in such cases is also considered. PMID- 11198318 TI - Endovascular treatment of a noninfected anastomotic juxtarenal aortic aneurysm. AB - An 82-year-old man underwent an endovascular procedure with a commercially available endovascular graft for an anastomotic juxtarenal abdominal aortic aneurysm. The anastomotic aneurysm, which showed no sign of infection, developed 4 years after implantation of an aortic end-to-end graft for an infrarenal aortic aneurysm. The aneurysm was diagnosed during routine ultrasonographic follow-up; there was no apparent infection of the graft. Aortography confirmed the diagnosis and also revealed a small pseudoaneurysm at the level of the distal aortic anastomosis. Endovascular surgery was performed in the operating room with the guidance of C-arm fluoroscopy and intravascular ultrasound. Two Vanguard Straight Endovascular Aortic Graft Cuffs (26 x 50 mm and 24 x 50 mm) were implanted, successfully excluding both the anastomotic juxtarenal aortic aneurysm and the distal pseudoaneurysm. The renal arteries were preserved and no early or late endoleaks were observed. The patient was discharged 2 days after the procedure. Sixteen months later, he was alive and well, with no endovascular leakage, no enlargement of the aortic aneurysms, and no sign of infection. In our opinion, this experience shows that commercially available endovascular grafts may be used successfully to treat anastomotic aortic aneurysms and pseudoaneurysms. PMID- 11198319 TI - Two-stage elephant trunk reconstruction for aneurysm of an aberrant right subclavian artery in association with aneurysmal distal aortic arch and descending thoracic aorta. AB - Surgical treatment of the combination of aneurysms of an aberrant right subclavian artery, distal aortic arch, and descending thoracic aorta requires control of structures in both the right and the left hemithorax. We report a 2 stage surgical approach. The 1st stage, performed through a median sternotomy, consists of an elephant trunk reconstruction and an interposition graft to the ligated aberrant right subclavian artery. The 2nd stage, performed through a left thoracotomy is an interposition graft from the elephant trunk to the distal descending thoracic aorta. PMID- 11198320 TI - Hydatid cyst in the interventricular septum: a rare cause of dizziness? PMID- 11198321 TI - Intermittent constriction of the ductus arteriosus in the fetus: a cause for concern? PMID- 11198322 TI - Curved sternotomy incision. PMID- 11198323 TI - Report on accreditation learning sets in the West Midlands region of the NHS. AB - This article reports on the evaluation of the first year of a project, which utilized learning sets to support librarians undergoing the accreditation process, in the health libraries in the West Midlands region of the NHS. The West Midlands Health region is divided up into education consortia patches. Each group of patch librarians was allocated a local accreditation facilitator. The groups met regularly to discuss problems and progress relating to their library's accreditation. The results of the evaluation suggest that this is a valuable approach to use. The recommendations state that regular, frequent meetings are needed. Extra training and guidance would help the facilitators to be more effective in their role. PMID- 11198324 TI - Canada's national initiative to advance access to electronic journals. AB - This paper describes a national experiment in the licensing of full text information in journals, primarily in the fields of science, technology and medicine. It discusses the initiative of the federal government of Canada through the creation of the Canada Foundation for Innovation as a new funding agency, with an objective of improving research and creativity in Canadian science. The successful efforts initiated by the Canadian Association of Research Libraries/Association des bibliotheques de recherche du Canada to create a funding opportunity to develop the 'information infrastructure' for Canadian researchers and the resulting Canadian National Site Licensing Project (CNSLP) progress is discussed. The evolution of a project governance structure to maintain the support of the 64 participating institutions is reviewed and the need to develop an appropriate exit strategy at the conclusion of the federal funding is also considered. PMID- 11198325 TI - Information and its value to health workers in rural Uganda: a qualitative perspective. AB - A study was conducted in 1998/99 to investigate the accessibility and use of information by health workers in rural Uganda. Data were collected qualitatively using semi-structured interviews. As a qualitative study, it focused in-depth on a relatively small sample of health workers selected purposefully. Different categories of health workers were interviewed. Data were analysed using a grounded theory approach. In this paper, two main categories that emerged from the data will be discussed, namely: value of information and constraints. Information was valuable in clinical work, information dissemination, decision making, administration and detection. Constraints to effective information use included the quality and relevance of the information as well as the difficulties of sometimes putting theory into practice. Finally, the concepts that emerged from the analysis of the use of information pointed directly to the information needs of the health workers studied, which shows that information was valuable in meeting those needs. Some implications of the study and areas for further research are highlighted. PMID- 11198326 TI - Improving the provision of traditional health knowledge for rural communities in Ghana. AB - In Ghana many rural illiterate people practise traditional medicine and spread their knowledge through oral communication among themselves. This paper observes that traditional health information which freely circulates, and is actively disseminated by healers in rural communities greatly contributes to the knowledge for preparing home remedies and other traditional interventions. Oral communication can give rise to inaccurate and even dangerous information where charlatans can penetrate and operate within the health system. The Danfa project, which involved verbal teaching of modern health techniques to illiterate herbalists, and educating villagers about improved traditional medical practices, is described as a success story of information provision for illiterates. The experience is applied to propose the modification of some training programmes under the Ministry of Health to produce traditional health care information providers. Repackaged information and the public media are recommended as the most effective method of transferring knowledge to those unable to read. PMID- 11198327 TI - Creating books for the National electronic Library for Health: expected barriers and useful lessons. AB - The National electronic Library for Health (NeLH) is now taking shape, as the virtual branch libraries begin to accumulate 'books', among their resources. In the Primary Care branch (http://www.nelh-pc.nhs.uk), one of the first available books was the Statement of Fees and Allowances (otherwise known as the Red Book). While being held up as an example of what the NeLH can offer, this book and the story of its transformation from paper to Internet format is a powerful example of how much further the National Health Service (NHS) must go before it can claim to be fully exploiting the benefits of information technology (IT). This article refers to the author's experience in producing electronic books for primary care using WaX software, and an example of a process change from paper to screen that was managed within a university administrative office. The author suggests that to reap optimal benefits from IT, the NeLH and its collaborators must address the fundamental issues of people and the paper-based processes used by information providers. The NeLH must work with both NHS IT trainers and information providers in a three-way collaboration involving key people and processes, to achieve the efficient production of an updateable and user-friendly library of electronic books. PMID- 11198328 TI - Qualitative research in health information user studies--a methodological comment. PMID- 11198329 TI - The Forest Healthcare Clinical Support Librarian: 6 months on. PMID- 11198330 TI - Access to reliable information for health workers in developing countries: information for all, starting at grass roots level in Africa. PMID- 11198331 TI - Primary care information management: 5 years of progress 1995-2000. A personal view. PMID- 11198332 TI - 'Clearly evident' a CD-ROM to teach junior doctors information skills. PMID- 11198333 TI - Research. Increasing the uptake of research findings by health librarians depends on two core skills. PMID- 11198334 TI - [Physical exercise: a little developed intervention in primary care]. PMID- 11198335 TI - [Quality analysis of clinical practice guidelines on cardiovascular risks in the Basque country and a proposal for their evaluacion]. AB - OBJECTIVES: To find the implantation and quality of clinical practice guidelines (CPG) to manage the major cardiovascular risks: tobacco dependency, hypertension, hyperlipaemia and diabetes mellitus. To work out a model to evaluate the quality of the CPG in primary care. DESIGN: Cross-sectional descriptive study. SETTING: The primary care centres of the Basque Country. PARTICIPANTS: 170 CPG used at present to manage the four mentioned cardiovascular risks. MEASUREMENTS AND MAIN RESULTS: Information was requested on the use of CPG and copies of their guidelines were requested from those in charge of 103 ranked centres. 77 centres replied (76%), of which 66 said they used one of them. A total of 170 CPG were received. On the basis of non-specific prior proposals for primary care, 21 quality criteria for the CPG, grouped in 6 blocks, were drawn up. Top quality was found in the block for clarity of clinical procedure with 63% compliance with the CPG, followed by general description (54%), and evaluation and measurement of impact (30%). The blocks with worst compliance were identification of people involved in their design (23%), evidence of their recommendations (19%) and conditions of application (4%). CONCLUSIONS: A model was proposed to evaluate the quality of the CPG. Major deficiencies in quality were found. These were most marked in key aspects such as bibliographic support for their recommendations, envisaging of conditions for application and identification of authors and reviewers. PMID- 11198336 TI - [Design of a method for the evaluation of clinical competence in primary care]. AB - OBJECTIVE: To measure clinical competence in primary care (PC). DESIGN: Descriptive cross-sectional study. SETTING: Six PC teams in Barcelona. PARTICIPANTS: 25 family doctors volunteering out of a total of 60. MEASUREMENTS AND MAIN RESULTS: Three simulated visits took place on three different days, allocated at random as a prior appointment for hypertension. Clinical competence was measured through the Miller criteria, a method with open short-reply questions combining the clinical interview with standardised patients (SP), review of clinical histories (CH) and doctor's self-evaluation (DS). The following components of competence (CC) were evaluated: anamnesis, physical examination, further tests, differential diagnosis, management, clinical history and communication. 22 doctors completed the study. Each CC was weighted by a group of experts, who also agreed two minimum levels of competence, 50% and 60%. Each doctor's final score was the result of the addition of each of the three cases divided by the maximum score possible. The CC values were always higher with SP than otherwise. 63.3% of doctors surpassed the 60% mark, and 90.9% the 50% mark. Internal consistency, measured with Cronbach's alpha, was 0.94, 0.73 and 0.67 for each clinical case. The kappa reproduction test was 0.25. CONCLUSIONS: The use of SP is a good method of evaluation, as it enables anamnesis, management of the patient, physical examination and communication to be assessed. The study is very reliable, with low reproduction, which is probably due to the few cases used. PMID- 11198337 TI - [Postcoital hormonal contraception: study on the attitudes and prescription of primary care physicians]. AB - OBJECTIVE: To study the understanding, attitudes and practice of primary care doctors in the prescription of hormonal post-coitus interception, along with the social and demographic, educational, legal and ethical variables associated with this prescription. DESIGN: Cross-sectional descriptive study. SETTING: Area IV de INSALUD in Asturias. PARTICIPANTS: Family doctors, excluding locums (n = 178). MEASUREMENTS AND RESULTS: An anonymous self-administered questionnaire with 33 questions, re-sent once, between November 1999 and February 2000. The association independence of variables was contrasted through the chi 2 test (a statistically significant association if p < 0.05). 77% responded, 51% of whom were men. Average age was 43 (SD = 6.69), with professional experience of 17 years worked (SD = 6.87). 47% were family doctors and 39% general practitioners. 85% worked in health centres; 46% in urban settings. 71% were catholics, 73% (95% CI: 66%-80%) had been asked on at least one occasion in the previous six months for the post coitus pill (PCP), with demand greater in the urban environment (83%). 18% considered the PCP an abortion method. 88% said they would prescribe it (95% CI: 82.5%-93.5%), of which 30% (95% CI: 16%-44%) did so according to WHO recommendations. 100% of the "non-prescribers" were catholics. CONCLUSIONS: Most doctors receive requests for the PCP and prescribe it on demand, though prescription varies with age, categories and, in particular, religious belief. Only a third prescribes according to WHO recommendations. PMID- 11198338 TI - [Comparison of primary care teams in Barcelona according to management formulas]. AB - OBJECTIVE: The aim of the study is to compare, among socio-economically similar areas, the use of medical services, clinical practice and pharmacy costs depending on the how the primary healthcare teams, that provide these services, are organized according to different managemental formulas. DESIGN: Descriptive study of the evaluation of health care services. PATIENTS AND METHODS: The population units (basic health areas) attended by the reformed primary health care services in Barcelona were classified into three levels according to the population's socioeconomic status (high, medium or low). For each level, two primary health care teams were selected representing different primary health care providers: "Institut Catala de la Salut"; and others. The influence of both the provision option and the population characteristics on service use, clinical practice and costs of prescription were compared. MAIN RESULTS: The services offered by the two provision options differ. However, the use of medical services is related to the socioeconomic characteristics and not to the option for service provision. Whilst there are no relevant differences in clinical practice between the different options, we observed variations among different primary care teams, notably in referrals to specialists and influenza vaccine coverage. The greater source of variation in prescription costs seems to be related to an external confounding factor. CONCLUSIONS: Empirical data have not identified relevant differences in the pattern of use, clinical practice, or costs between the different options for service provision within the model of reformed primary care services. Observed variations seem to be associated mainly with the population's characteristics, its pattern of health service use or other external confounding factors. PMID- 11198339 TI - [Nocturnal drop of arterial blood pressure: determinant factors and relationship with organic damage secondary to hypertension]. AB - OBJECTIVES: To evaluate the night-time drop in blood pressure in patients with light hypertension and to determine its possible relationship with damage in key organs. DESIGN: Cross-sectional study. SETTING: Eight urban health centres. PATIENTS: Four hundred and eighteen adults with light-moderate hypertension. INTERVENTIONS: a) Blood pressure reading on three visits; b) ambulatory monitoring of pressure for 24 hours; c) echocardiograph (in 219 patients); d) albuminuria determination (in 134 patients). A night-time drop in blood pressure was defined as the difference between day and night ambulatory pressures; and relative drop, as the night-time pressure drop as a percentage of the day-time pressure. RESULTS: Night-time drop in systolic and diastolic pressures was 13.6 (10.7) and 12.1 (8.6) mmHg, respectively. The predictive factors of night-time drop in blood pressure were, directly, daily ambulatory blood pressure (p < 0.05) and female gender (p < 0.05) and, inversely, age (p < 0.05). No association was observed between night-time drop in blood pressure and left ventricular mass. Only in women was an independent relationship found, inversely, between night time drop in blood pressure and urinary excretion of albumin (p < 0.05). CONCLUSIONS: Relative night-time drop in blood pressure is greater in women than in men, diminishes with age and depends on the day-time ambulatory pressure. In women a minor night-time drop in blood pressure is associated with greater organic damage. PMID- 11198340 TI - [Are occupation and education interchangeable as social indicators in community health? A study in an employed population]. AB - OBJECTIVE: Epidemiological studies and interventions to reduce inequalities in community health require the assignation of exhaustive and easy-to-obtain social indicators. Occupation and education are two of the most often used. In this study we attempt to evaluate the association between education and occupation among adult working population because if, in the absence of one of these two variables, it will be feasible to use the remaining with the lesser lost of socio economic information. DESIGN: From a representative sample (n = 3091) of general population (18-65 years old) drawn out from a prevalence survey on chronic disease risk factors performed in the Region of Murcia, a log-lineal analysis has been made between education and occupation among working people (65.8% of males and 34.2% of females from the original sample). RESULTS: Men present significant association between managerial positions and university education. The association drops between clerks and high school graduates to increase among all manual workers with or without primary schooling education. Among women--with a lesser number of participants--the education/occupation association describes the same pattern but with higher magnitudes in the positive associations between managerial positions and university education. For both genders, the greatest associations are found in both diagonals of the education by occupation tables indicating: better occupation, more education, and the opposite. CONCLUSIONS: The classification of working people according to education and occupation presents association, internal consistency and gradient. In absence of comprehensive information regarding occupation, education could be an alternative as socio economic indicator. PMID- 11198341 TI - [Home chronic illness and consumption of psychopharmaceuticals]. AB - OBJECTIVE: To assess the consumption of psychiatric drugs by chronic homebound patients. DESIGN: Descriptive, longitudinal study. SETTING: Raval Nord Health District, Barcelona. PATIENTS AND OTHER PARTICIPANTS: All 243 chronically ill homebound patients registered on the home care programme in May 1996. After three years 16% had gone into a home, 9% had moved residence, 38% had died, and 37% remained active. MEASUREMENTS AND MAIN RESULTS: Of the 90 patients still active, 40% took some psychiatric drug in May 1999. 8% of the patients who said they had taken psychiatric drugs did so by self-medication. The most commonly consumed pharmacological group of the psychiatric drugs were benzodiazepines at 64%. Women took more psychiatric drugs (45%), as did persons living alone or who had been bereaved (50%). The proportion of patients taking psychiatric drugs was greater when there was worse autonomy according to the Katz index (67%), a cognitive deficit on the Short Portable Mental Status Questionnaire (SPMSQ) of Pfeiffer (62%), and in the presence of comorbidity (56%) (p < 0.01). CONCLUSIONS: There is high consumption of psychiatric drugs by chronic homebound patients, especially when there is physical-cognitive deterioration and presence of comorbidity. PMID- 11198342 TI - [Effectiveness, strategies and successes in weight loss in function of anthropometric parameters]. AB - OBJECTIVES: To find the variability in women's appearance at three moments of their life cycle and its relationship with practices aiming at weight loss, analysing the efficacy of this behaviour. DESIGN: Cross-sectional. SETTING: Women from the Community of Madrid who formed part of an investigation by the Unit of Anthropology of the Department of Biology of the Autonomous University of Madrid (UAM) into perception of image and associated behaviour as a function of age, body mass index, and social and economic conditions. PARTICIPANTS: 535 women in three age groups: 200 adolescents belonging to two secondary schools in Madrid; 202 university students from the Biology Faculty of the UAM, and 135 women aged between 45 and 65 and living in the Madrid area of Alcobendas, who were taking part in a women's health programme run by the Alcobendas town council. MATERIAL AND METHODS: Information was collected on body measurements, self-perception and image assessment, with perception indicators and body form indicators contrasted. RESULTS: There were a great many attempts to lose weight by adolescents and women over 45, with the starting age for such practices much earlier in the adolescents' and students' groups. It was particularly striking that 44% of the adolescents within the thin category had tried to lose weight. Among the students and women over 45 this percentage rose in consonance with their overweight. The older women were more effective at losing weight, but it was very difficult for them to maintain this loss. The speed of weight loss was higher in women with higher body mass index. CONCLUSIONS: Physical appearance varies between young women and women over 45, in that the former are taller, thinner and with a straighter figure. Despite this, young women develop behaviour designed to lose weight much more often than older women, with an earlier starting age and more rapidly, which can have serious health consequences. PMID- 11198343 TI - [Validity of the declared tobacco consumption in pregnancy]. AB - OBJECTIVES: To analyse the relationship between the stated consumption of tobacco by pregnant women who say they smoked before pregnancy and the levels of cotinine in their urine at the start and end of pregnancy. DESIGN: Observational, longitudinal study. PARTICIPANTS: During 1997. STUDY GROUP: 147 pregnant women at their first pre-natal visit to outclinics of the Hospital del Mar. CONTROL GROUP: 50 non-smoker pregnant women monitored during their pregnancy. MEASUREMENTS AND MAIN RESULTS: The numbers of cigarettes per day that they said they smoked on their first monitoring visit to our centre and at the last attendance before giving birth were recorded. Cotinine levels in the urine samples taken on these visits were measured. Mean cotinine in pregnant women who said they had given up smoking was higher than in non-smokers. There was a statistically significant linear relationship between the number of cigarettes stated and cotinine levels at the first and last pregnancy monitoring visits, as well as between the variation in the number of cigarettes and cotinine levels at these two visits. The negative predictive value of what they said about their tobacco habit was 82.9%. CONCLUSIONS: There was a certain under-declaration by pregnant smokers, although their statements of consumption and cotinine levels correlated closely. The under-declaration did not increase despite reiterated advice to stop smoking, which means that, despite its limitations, it could be a useful indicator for evaluating the effect of interventions aimed at stopping women smoking during pregnancy. PMID- 11198344 TI - [Rational use of rofecoxib]. PMID- 11198345 TI - [New drugs or therapeutic novelties? El Comite de Evaluacion de Nuevos Medicamentos del Instituto Catalan de Salud]. PMID- 11198346 TI - [The family physician and elderly abuse syndrome]. PMID- 11198347 TI - [All that glitters is not hysteria]. PMID- 11198348 TI - [Antibiotic resistance: a public health problem]. PMID- 11198349 TI - [AMPA (AutoMonitoring of Arterial Pressure) and MAPA (Ambulatory Monitoring of Arterial Pressure]. PMID- 11198350 TI - Post-injury multiple organ failure: the role of the gut. AB - Despite intensive investigation, the pathogenesis of post-injury multiple organ failure (MOF) remains elusive. Laboratory and clinical research strongly suggests that the gastrointestinal tract (i.e., the gut) plays a pivotal pathogenic role. Since its inception in 1988, the Trauma Research Center (TRC) at the University of Texas-Houston Medical School (UTHMS) has focused its efforts on elucidating the role of the gut in post-injury MOF. On the basis of our observations and those of others, we believe that 1) shock with resulting gut hypoperfusion is an important inciting event, 2) the reperfused gut is a source of proinflammatory mediators that can amplify the early systemic inflammatory response syndrome (SIRS) and thus contribute to early MOF, 3) early gut hypoperfusion causes an ileus in both the stomach and small bowel that sets the stage for progressive gut dysfunction so that the proximal gut becomes a reservoir for pathogens and toxins that contribute to late sepsis-associated MOF, and 4) late infections cause further worsening of this gut dysfunction. Thus, the gut can be both an instigator and a victim of MOF. The purpose of this article is to provide the rationale behind these beliefs and to provide a brief overview of the ongoing research projects in the TRC at UTHMS. PMID- 11198351 TI - Decreased oxidant buffering impairs NF-kappaB activation and ICAM-1 transcription in endothelial cells. AB - The DNA binding activity of the transcription factor, NF-kappaB, is regulated by the phosphorylation and degradation of its inhibitory protein, IkappaB, and post translational modification involving redox reaction of a cysteine residue (Cys62) of NF-kappaB. We addressed the role of the redox state of endothelial cells in modulating TNFalpha-induced NF-kappaB activity. The effects of TNFalpha on DNA binding activity of NF-kappaB and expression of mRNA encoding ICAM-1 (an NF kappaB-activated gene) were studied in human pulmonary artery endothelial (HPAE) cells under basal conditions and after decreasing the intracellular glutathione (GSH) concentration. HPAE cells were treated with buthionine sulfoximine (BSO) (16 h), an inhibitor of GSH synthesis, which caused concentration-dependent decreases in GSH concentration. Stimulation of control cells with TNFalpha resulted in reactive oxygen species (ROS) generation and activation of NF-kappaB binding to the ICAM-1 promoter and ICAM-1 transcription. However, stimulation of GSH-depleted cells with TNFalpha resulted in ROS accumulation secondary to the decreased ROS buffering capacity, and marked impairment of NF-kappaB-binding activity and ICAM-1 mRNA expression. Exposure of BSO-treated cells to the reducing agent dithiothreitol (DTT) before TNFalpha treatment or supplementation of nuclear extract (isolated after TNFalpha challenge of BSO-treated cells) with DTT significantly augmented the effect of TNFalpha on NF-kappaB-binding activity and ICAM-1 mRNA expression. Thus the oxidative modification of NF-kappaB secondary to the loss of ROS buffering capacity may regulate NF-kappaB binding to ICAM-1 promoter, and thereby ICAM-1 transcription in endothelial cells. PMID- 11198352 TI - Under-resuscitation of near-lethal uncontrolled hemorrhage: effects on mortality and end-organ function at 72 hours. AB - Laboratory studies of uncontrolled hemorrhage demonstrate that under resuscitation (UR) improves short-term survival, but at the expense of tissue perfusion. The long-term effects of UR have not been studied. The purpose of this study was to evaluate survival and the incidence of end-organ injury (EOI), 3 days following moderate and severe UR of uncontrolled hemorrhage. Thirty-four swine (14-24 kg) were assigned to 4 groups: Groups I, II, and III were hemorrhaged to a pulse pressure = 5 mmHg in the presence of a 4-mm aortic tear: Group I (control; n = 6) was not resuscitated; Group II (n = 11) was severely under resuscitated (MAP [mean arterial pressure] = 40 mmHg) for 75 min; Group III (n = 9) was moderately under resuscitated (MAP = 60 mmHg) for 75 min. After 75 min, the aortotomy was repaired, and animals were resuscitated to baseline physiologic parameters. Group IV (sham; n = 8) was instrumented, but not hemorrhaged. Seventy-two-hour mortality was 100%, 36%, 22%, and 0% for Groups I through IV (P = .001 Fisher's exact). Cardiac indices, serum bicarbonate, and systemic oxygen delivery were significantly lower in Group II as compared to Group III during the 75 min of UR (P < 0.05; repeated measures ANOVA). By 72 h, physiologic parameters in surviving animals had returned to baseline levels. Measures of kidney, liver, neurologic, and pulmonary function did not change from baseline. There was no histologic evidence of EOI. In this model, 75 min of UR did not result in EOI. There was a trend toward greater survival, and tissue perfusion was better preserved with moderate as compared to severe UR. PMID- 11198353 TI - Modulation of organ ICAM-1 expression during IV-TPN with glutamine and bombesin. AB - The gut primes neutrophils (PMNs) during injury, which can then induce distant organ damage after a second insult. ICAM-1 is an important adhesion molecule in PMN attachment to the vascular endothelium. Parenteral nutrition (TPN) decreases gut levels of interleukin (IL)-4 and IL-10, two cytokines that are normal inhibitors of ICAM-1 expression. TPN also increases gut ICAM-1 expression and PMN accumulation. Since glutamine (GLN) and bombesin (BBS) prevent TPN-associated impairment of mucosal immunity, we hypothesized that GLN and BBS would modulate organ ICAM-1 expression in association with normalization of IL-4 and IL-10 levels. Forty-four mice were fed chow, TPN, or GLN-TPN (isonitrogenous 2% GLN enriched TPN). After 5 days of diets, ICAM-1 expression was quantified in organs using the dual radiolabeled monoclonal antibody technique. In the next experiment, 29 mice were fed chow, TPN, or BBS-TPN (BBS 15 microg/kg TID) for 5 days to measure organ ICAM-1 expression. Total IL-4 and IL-10 levels were measured with ELISA from intestinal homogenates of another set of 52 mice fed chow, TPN, GLN-TPN, or BBS-TPN. TPN significantly increased ICAM-1 expression in the lung, kidney, and intestine compared with chow mice. GLN-TPN decreased intestinal, but not lung, ICAM-1 expression, while BBS-TPN reduced pulmonary, but not gut, ICAM-1 levels. GLN- and BBS-TPN returned gut IL-4 levels to normal, but failed to increase IL-10 levels. GLN and BBS had different effects on organ ICAM 1 expression induced by lack of enteral nutrition. Mechanisms other than recovery of IL-4 alone may be responsible for gut ICAM-1 expression. PMID- 11198354 TI - TNF mediates a murine model of Addison's crisis. AB - Addison's crisis is the most serious complication of adrenal insufficiency. To elucidate the mechanism of this disorder following infection, the role of TNF in adrenalectomized murine models of Addison's crisis and Addison's disease (chronic hypoglucocorticoidism) were examined. Adrenalectomy conferred a 40-fold increased sensitivity to the lethal effects of lipopolysacharride (LPS) (P < .001). Enhanced sensitivity to LPS was found to increase with duration of adrenal insufficiency (P < .02). Enhanced lethality to heat-killed Streptococcus pneumonia was also demonstrated (P < 0.02). Necropsy of endotoxin-killed adrenalectomized mice demonstrated similar pathologic findings to those found by others when the control mice were administered a lethal dose of either LPS or TNF. Adrenalectomized TNF receptor Ia and Ib double null mice were demonstrated to be resistant to the lethal effects of LPS (P < 0.02). Pretreatment with anti TNF, but not control antisera, was found to prevent death in LPS-treated wild type adrenalectomized mice as well (P < 0.02). Studies into the mechanism by which TNF was precipitating Addison's crisis demonstrated enhanced sensitivity to TNF (3-fold; P < 0.02), and a marked increase in serum TNF concentration (approximately 5-fold; P < 0.001) following LPS challenge. The effect of TNF upon long-term survival in adrenalectomized mice was examined in TNF-receptor Ia- and Ib-deficient mice. Deficiencies in either the TNF-receptor Ia or Ib was noted to confer a survival advantage relative to colony controls following adrenalectomy (P < 0.02). In summary, both LPS-induced Addison's crisis and chronic adrenal insufficiency are disorders of TNF disregulation. Based upon these data, therapeutic strategies targeted at controlling TNF in adrenal insufficiency are suggested. PMID- 11198355 TI - Spectral changes in systemic arterial pressure signals during acute mevinphos intoxication in the rat. AB - We investigated the cardiovascular consequences of acute intoxication by the organophosphate poison, mevinphos (Mev), and delineated the underlying mechanism. Based on on-line power spectral analysis of systemic arterial pressure (SAP) signals in rats anesthetized and maintained by propofol, we identified two distinct phases after intravenous administration of Mev (160 or 320 microg/kg). Phase I was characterized by transient hypertension and mild tachycardia, concurrent with an increase in the very high-frequency (BVHF; 5-9 Hz), high frequency (BHF; 0.8-2.4 Hz), low-frequency (BLF; 0.25-0.8 Hz),and very low frequency (BVLF; 0-0.25 Hz) components of SAP signals. Phase II exhibited significant hypotension, a reversal of the BVHF and BVLF power to control levels, and further reduction in the power density of both BHF and BLF components to below baseline. Microinjection of Mev (2 microg) into the bilateral nucleus reticularis ventrolateralis (NRVL), the medullary origin of sympathetic neurogenic vasomotor tone, essentially duplicated those phasic cardiovascular changes. Similarly, sympathoexcitatory NRVL neurons exhibited respectively an elevation and a decline in their spontaneous activities during Phase I and Phase II Mev intoxication. We conclude that the progressive accumulation of acetylcholine over time induced by a direct inhibition of Mev on cholinesterase in the NRVL may be responsible for the phasic changes in cardiovascular events over the course of acute Mev intoxication. Whereas the initial amount of acetylcholine is excitatory to NRVL neurons, overstimulation by the amassed acetylcholine results instead of an inhibitory action. PMID- 11198356 TI - Evolution of an immune suppressive macrophage phenotype as a product of P38 MAPK activation in polymicrobial sepsis. AB - Studies indicate that polymicrobial sepsis in humans and animals is characterized by a biphasic response, which is dominated early by proinflammation, but over time develops into a state of generalized anti-inflammation (depressed Th1 cell response and decreased macrophage (M0) capacity to release proinflammatory cytokines). However, with respect to the macrophage, it remains unknown what mechanism(s) controls this change. In this regard it is well documented that the p38 mitogen activated protein kinase pathway (MAPK) plays a central role in the regulation of Mphi functions. However, the contribution of p38 MAPK activation to the loss of these Mphi functions in polymicrobial septic animals remains unknown. To determine this we induced polymicrobial sepsis in C3H/HeN male mice using cecal ligation and puncture (CLP). Twenty-four hours post-CLP, during the late, immune-suppressed stage of sepsis, splenic and peritoneal Mphi were harvested, stimulated with lipopolysaccharide (LPS), and the activation of p38 MAPK assessed. In Mphi from CLP mice, p38 MAPK activity was markedly increased. To determine the extent that these changes in p38 MAPK had an impact on Mphi immune function, cells were pretreated with 10 microM of the p38 MAPK inhibitor, SB203580, or with DMSO vehicle, and subsequently stimulated with LPS. IL-10, IL 6, IL-12, and nitric oxide release was determined. Our results indicate that with LPS stimulation alone, there was a marked increase in the release of the anti inflammatory mediator, IL-10 after CLP. Alternatively, proinflammatory IL-12 and IL-6 release was suppressed. Treatment with SB203580 suppressed the increase in IL-10 release seen after CLP, while partially restoring IL-12 secretion. IL-6 release was partially restored only in splenic macrophages treated with SB203580. To the extent that these in vitro findings could be translated to an in vivo setting, we assessed the in vivo effects of p38 MAPK inhibition on survival. Mice were given 100 mg of SB203580/kg body weight or saline vehicle (intraperitoneal) either immediately post-CLP or 12 h post-CLP. Delayed administration of SB203580 significantly improved survival, while also preventing the increased NO and IL-10 release and improving IL-12 release by macrophages. These results suggest that p38 MAPK pathway plays a critical role in the induction of an immune-suppressive macrophage phenotype, and that inhibition of p38 MAPK markedly improves survival following polymicrobial sepsis. PMID- 11198357 TI - Calcium uptake by sarcoplasmic reticulum is impaired during the hypodynamic phase of sepsis in the rat heart. AB - Alterations of the ATP-dependent Ca2+ uptake in the cardiac sarcoplasmic reticulum (SR) during the 2 hemodynamically distinct phases of sepsis were investigated. Sepsis was induced by cecal ligation and puncture (CLP). Control rats were sham-operated. The SR vesicles were isolated by sucrose gradient centrifugation. The results show that the rates of ATP-dependent Ca2+ uptake in the cardiac SR were unaffected during the early hyperdynamic phase, whereas they were decreased by 41-46% (P < 0.01) during the late hypodynamic phase of sepsis. Analysis of the kinetics of Ca2+ transport indicates that during the late phase of sepsis, the Vmax values of Ca2+ pump for ATP and Ca2+ were decreased, whereas the affinities of Ca2+ pump for ATP and Ca2+ were unaffected. Magnesium stimulated, whereas vanadate inhibited the ATP-dependent Ca2+ uptake, but the Mg2+-stimulated and the vanadate-inhibited Ca2+ uptake activities were significantly lower during the late sepsis. Phosphorylation of SR by the cAMP dependent and the calmodulin-dependent protein kinases stimulated the ATP dependent Ca2+ uptake in the control and the early septic experiments, whereas it failed to stimulate Ca2+ uptake in the late sepsis. The extent of the phosphorylation-stimulated Ca2+ uptake activities was reduced by 65-69% (P < 0.01) during the early sepsis, and they were completely abolished during the late sepsis. These data indicate that the ATP-dependent Ca2+ uptake in cardiac SR was impaired during the late hypodynamic phase of sepsis. The impaired Ca2+ uptake during late sepsis was associated with a defective phosphorylation of SR proteins. Because the ATP-dependent Ca2+ uptake by cardiac SR plays an important role in the regulation of contraction-relaxation coupling, our findings may contribute to the understanding of the pathogenesis of altered cardiac function during the progression of sepsis. PMID- 11198358 TI - Pmax, end systolic elastance, and Starling's law of the heart. AB - Starling's law is a description relating the energy released by the contracting ventricle to the end diastolic fiber length. The peak systolic pressure during isovolumic contraction is an example of this relationship; Sunagawa and coworkers (12) termed that pressure Pmax. It may also be estimated during ejecting beats. Here we compare the variable Pmax at a given end diastolic volume with that of end systolic elastance as an indicator of ventricular function, changes in either being indicative of changes in the inotropic state of the heart. We specifically investigate 2 points on the end systolic pressure-volume relationship (ESPVR) plot: 1) the Pmax, EDV point, obtained from the concept of the maximum pressure, Pmax, the pressure an isovolumically contracting ventricle would produce at a given end diastolic volume (EDV); and 2) the end systolic pressure, end systolic volume point. Both points would be expected to shift proportionally with changes in the slope of ESPVR. Data were obtained from 2 published reports in humans in the literature and from a group of 5 dogs subjected to a wide range of preloads and afterloads. High correlations (>0.9) were obtained for changes in the slope of ESPVR and the Pmax, EDV points. The latter, a more readily obtainable variable from single ejecting beats, is proposed as a version of Starling's law, the changes in which are directly comparable with the changes in end systolic elastance. The changes in the end systolic pressure, end systolic volume points, were not as reliable (<0.7). PMID- 11198359 TI - Acute hemodynamic effects of induced hypothermia in hemorrhagic shock: an experimental study in the pig. AB - Hypothermia (HT) is used in certain surgical procedures to reduce metabolism and protect the brain, but in trauma victims accidental HT is considered harmful. Recent animal studies indicate that HT has protective effects in hemorrhagic shock. The aim of the present study was to examine how induced HT modifies the hemodynamic pattern in hemorrhagic shock. Twenty pigs with a body weight of between 17 and 24 kg (mean 20.8) were anesthetized, 50% of their blood volume was withdrawn, and hypothermia (30 degrees C) was induced in half of them (HT group) while the others served as controls. Central hemodynamics was monitored during 4 h via an arterial line and a pulmonary artery catheter. Blood samples were obtained for measurement of leukocyte and platelet counts. Three of the control pigs died while all the animals in the HT group survived the experiment. The hemorrhage resulted in a marked increase in heart rate and a drop in cardiac output and mean arterial pressure. HT slowed the heart rate and induced a further reduction of cardiac output, which parallelled the depression of the core temperature, while the stroke volume did not change in any of the groups. A significant decrease in mean arterial pressure and the leukocyte count became apparent 2 h after the induction of HT. HT aggravated the hypokinetic situation resulting from hemorrhagic shock but without increasing the mortality. PMID- 11198360 TI - Differential roles of iNOS and nNOS at rostral ventrolateral medulla during experimental endotoxemia in the rat. AB - We investigated the differential contribution of inducible and neuronal nitric oxide synthase (iNOS and nNOS) at the rostral ventrolateral medulla (RVLM) to endotoxemia induced by E. coli lipopolysaccharide (LPS). In Sprague-Dawley rats maintained under propofol anesthesia, i.v. administration of LPS (15, 30, or 45 mg/kg) induced a reduction (phase I), followed by an augmentation (phase II) and a secondary decrease (phase III) in the power density of the vasomotor components (0-0.8 Hz) in systemic arterial pressure (SAP) signals. LPS also induced an immediate hypotension, followed by a rebound increase and a secondary decrease in SAP. In addition, the level of iNOS mRNA exhibited a significant surge that began with phase I endotoxemia, reaching progressively its peak at phase III. Discernible down-regulation of nNOS mRNA was not detected until the last phase of endotoxemia. Pretreatment with microinjection of the selective iNOS inhibitor, aminoguanidine (250 pmol), into the bilateral RVLM significantly prolonged phases II and III endotoxemia, blunted the initial and secondary hypotension, and antagonized the upregulation of iNOS mRNA. Similar pretreatment with the selective nNOS inhibitor, 7-nitroindazole (1 pmol), on the other hand, discernibly shortened phase II and prolonged phase III endotoxemia, and induced progressive hypotension by antagonizing the rebound increase in SAP. We conclude that the relative prevalence of functional expression and molecular synthesis of iNOS over nNOS in the RVLM may be a crucial determinant for the reduction or loss in power density of the vasomotor components of SAP signals during experimental endotoxemia. PMID- 11198361 TI - Effect of sodium arsenite on iNOS expression and vascular hyporeactivity associated with cecal ligation and puncture in the rat. AB - Induction of the heat shock response protects animals from either endotoxemia or peritonitis. In endotoxemia, heat shock protein (HSP) induction is associated with reversal of vascular hyporeactivity and inhibition of iNOS expression. Recent studies suggest differences in the inflammatory mechanisms during endotoxemia and peritonitis animal models and their response to therapeutic interventions. We therefore studied the effect of the HSP inducer sodium arsenite (SA) on vascular reactivity and iNOS expression in rats undergoing cecal ligation and puncture (CLP). CLP resulted in suppression of the pressor effect of norepinephrine (NE) in vivo (measured by changes in blood pressure in response to NE boluses) and ex vivo (changes in contraction force in isolated mesenteric arteries in response to NE concentrations), and in the expression of iNOS protein. Pretreatment of the rats with SA resulted in reversal of CLP-induced vascular hyporeactivity in vivo and ex vivo, and inhibition of iNOS expression after 22 h. SA pretreatment improved 7-day survival after CLP from 18.2% to 70% (P < 0.005). Glucocorticoid receptor inhibition did not affect the effect of HSP induction on iNOS expression. The similarity of the effect of HSP on vascular reactivity and iNOS expression in two distinct sepsis models suggests that this effect may be clinically important and that a causative relationship between HSP induction, iNOS inhibition, and reversal of vascular reactivity is likely. PMID- 11198362 TI - Production of interleukin-12 is under the control of endogenous interleukin-10 in myocardial ischemia-reperfusion. AB - Interleukin (IL)-12 is a heterodimeric cytokine that is secreted mainly by antigen-presenting cells and plays a key role in determining the nature of immune response to exogenous or endogenous antigens. Negative regulators of IL-12 production include IL-10. With use of wild-type and IL-10-deficient mice, the aim of the current investigation was to determine whether IL-12 is produced in myocardial reperfusion injury and whether endogenous IL-10 modulates its production. IL-10 levels were significantly higher than baseline at both 2 h and 6 h after the start of the reperfusion. In the IL-10-deficient animals, no IL-12 could be detected in the plasma. In the wild-type animals, at baseline, and at 1 6 h after myocardial ischemia-reperfusion, no detectable increases in IL-12 were measured. However, in the IL-10-deficient mice, a significant and pronounced increase in IL-12 was detected. IL-10-deficient mice also exhibited significantly higher mortality during reperfusion than wild-type animals. We conclude that the production of IL-12 in myocardial reperfusion injury is dramatically affected by the levels of endogenous IL-10. PMID- 11198363 TI - The circumoval precipitin reaction in Fasciola. Detection of shell pores by scanning electron microscopy. AB - Precipitation reaction was detected around Fasciola eggs containing mature miracidia when they were incubated for 20 minutes with the sera of acute and chronic fasciolosis patients. The reaction was of the bleb type. The amount of blebs formed around the eggs was greater in case of acute than chronic fasciolosis. Scanning electron microscopy illustrated pores in the shell of Fasciola eggs. It is probable that the metabolic antigen passes through these pores leading to the positive circumoval precipitin reaction in cases of Fasciola infection. Antibodies specific to Fasciola excretory/secretory (E/S) egg antigens were not detected in the sera of Schistosoma cases. PMID- 11198364 TI - Immunohistochemical nuclear staining for P53 in nodular scabies. AB - Fifty patients with scabies were included in this study. Clinical, parasitological and histopathological study of all patients was done. P-53 expression was examined, using immunohistochemical techniques. Biopsies of nodular scabies showed atypical changes in the epidermis, the dermis showed dense inflammatory infiltrate. Focal positivity for P-53 have been demonstrated which could favour premalignant changes, and recommend further investigations. PMID- 11198365 TI - Toxocara canis: determination of the origin of antigenic materials released from infective larvae. AB - Indirect fluorescent antibody test (IFAT) revealed antigenic focal areas in the brain tissues of mice infected by Toxocara canis as determined by the light, electron and fluorescent microscopic examination of the infective larvae. The oesophageal gland was well defined and its secretory activity was evident. The oral orifice and the lumen of oesophagus were strongly fluorescing by using anti ES serum. These indicate the antigenic property of oesophageal gland secretion. Intestine appeared to be non-functional. There was a well-developed "H" shaped excretory cell with two lateral excretory columns. The sharing of the excretory system in released antigenic materials was evident by the fluorescence of its pore onto the parasite surface. An electron dense coat that covered the surface of the larva may be formed by products released from the oesophageal gland and the excretory system. Shedding of the outer larval surface was detected by IFAT at 37 degrees C. PMID- 11198366 TI - IgM and IgG cystatin capture enzyme linked immunosorbent assays: a tool for serodiagnosis and assessment of cure of acute fascioliasis after triclabendazole (TCZ; Fasinex) therapy. AB - This study included 71 individuals: 25 patients with confirmed acute fascioliasis, 9 patients with suspected fascioliasis, 27 patients with parasitic infections other than fascioliasis and 10 normal controls. Patients with fascioliasis were treated with TCZ as a single dose and followed up 1 and 4 months after therapy. The results showed that both IgM and IgG cystatin capture ELISAs had very high sensitivity and specificity of 100%. They were also able to diagnose early fascioliasis even before indirect haemagglutination test (IHAT) became positive. Within 4 months after treatment, only 20 patients (80%) with fascioliasis were cured as evidenced clinically, by normal eosinophil count and negative IHAT. After the first month of treatment, IgM and IgG cystatin capture ELISAs became negative in 16.6% and 83.3% of the cured cases respectively, reaching 95% for both assays after 4 months. They remained positive in 5 cases (20%) not responding to treatment. PMID- 11198367 TI - Evaluation of the in-vitro pediculicidal action of four known insecticides and three medicinal plant extracts. AB - Human lice is an increasing community health problem worldwide. This is particularly true among school children who spend most of their daytime in crowded areas. Four commercially known insecticides and three medicinal plant extracts were studied to evaluate their pediculicidal activities in-vitro. The best result with insecticides was achieved with malathion (Lt5o 10.396 and slope function 1.183). The best result with medicinal plant extracts was achieved with neem oil (A. indica) (Lt5o 85.27 and slope function 1.480). Although, neem oil extract was less active than malathion, yet it is more safe for human usage. PMID- 11198368 TI - A comparison between human, crustacean and bivalve isolates of Microsporidia. AB - Identification of Microsporidia detected in diarrhoeic stool of human and from press preparation of crabs, and bivalves muscles was done by staining with Giemsa, modified trichrome and H & E stains respectively. Positive samples were isolated & used for infection of 3 groups of mice viz group A human isolate, group B crab & group C bivalve isolates. Parasitological and histopathological studies using light and transmission electron microscopy (TEM) were done for samples from each group. The results clarified that human, crab & bivalve Microsporidia isolates showed common features. They were found in the supranuclear region of enterocytes. The stages observed were meronts, sporonts and free spores. Each spore was 1-2 um in length containing a single nucleus, a vacuole and a polar filament. Further genetical and biochemical studies will be undertaken to confirm the similarity or differences between these isolates. PMID- 11198369 TI - Cryptosporidiosis in Benha, study of some recent modalities in diagnosis and treatment. AB - A total prevalence of cryptosporidiosis was carried out on 1087 diarrheal patients of all age groups attending the outpatient clinics using modified Ziehl Neelsen stain (MZN) and Meriflour direct immunofluorescent technique (IFA). IFA was more sensitive, specific and gave positive results 19.5% than MZN stain which gave a positivity 13.5% Cases were divided into 3 groups, each group was treated by one of nitazoxanid (NTZ), or co-trimoxazole or placebo. The most effective drug was NTZ which cured 39 patients (79.6%) out of 49 patients followed by co trimoxazole that gave cure of 20 (41.6%) out of 48 patients. Placebo cured 20 (40%) out of 50 patients. PMID- 11198370 TI - Two contagious ectoparasites in an orphanage children in Nasr City, Cairo. AB - Lice and scabies are the main ectoparasites transmitted by contagious, particularly among children living in crowded areas. Examination of an orphanage children (both sex, 2-6 years old), showed infestation with head louse (64.1%), body louse (53.8%) and scabies (26.9%). The results were discussed on the light of the work done before. PMID- 11198371 TI - A novel chemotherapeutic combination for Trichomonas vaginalis targeting purine salvage pathways of the parasite. AB - A novel combination of chemotherapy (Dipyridamole/Allopurinol) targeting the possible purine salvage mechanisms of Trichomonas vaginalis was used in this study. The possible effect of these drugs either individually or in combination, on the multiplication of T. vaginalis in modified TYM axenic culture, was assessed on 24 hours intervals. The combination of both drugs at concentrations of 5 microM and 10 microM each showed a potent lethal effect on the parasite and an almost complete inhibition of parasite multiplication in culture. Each drug, individually, has a significant but partial inhibitory effect on parasite multiplication. Surprisingly, allopurinol, a competitive inhibitor of hypoxanthine, a nucleobase that is not salvaged by the parasite, showed a more potent inhibitory effect on parasite multiplication than dipyridamole, a specific inhibitor of the transport of adenosine, a favored nucleoside to T. vaginalis. However, the inhibitory effect of either drugs declines with time in contrast with that of the combination of both drugs which continues throughout all time points of the experiment. These results prove that a combination of dipyridamole and allopurinol could be useful, not only in the treatment of trichomoniasis, but also in other parasites that are unable of de novo purine synthesis. PMID- 11198372 TI - The effect of ivermectin on Cryptosporidium parvum in experimentally infected rat. AB - Ivermectin, (=ivomec) a broad spectrum antiparasitic agent has become a promising drug for treating wide range of parasitic infection and infestation. This study was carried out to investigate its activity against cryptosporidiosis in a rat model. The results showed that ivermectin is effective at a dose of 200 mg/kg. PMID- 11198373 TI - Trichinella encysted larvae in slaughtered pigs in Cairo (1995-1999). AB - Trichinosis is one of the most serious meat borne parasites. Examination of pigs in the slaughtered houses over the last five years showed an overall rate of 1.691%. The trichinoscope and sometimes the muscle digestion technique were adopted to diagnose infection. Trichinosis as a zoonotic parasitic disease was discussed. PMID- 11198374 TI - Preliminary observations on cross-mating of the malaria vector, Anopheles sergentii from two Egyptian oases. AB - Intra- and inter-strain crosses were made between randomly collected adults Anopheles sergentii originated from Tersa village (El-Faiyum Governorate) and Siwa oasis (Matruh Governorate). The success of such crosses and their effects on fecundity and fertility of the parental females and on survival and development velocities of the F1 immatures were examined. No overall heterosis effects on such attributes were detected suggesting absence of genetic differences between the vector populations in these two malarious areas. PMID- 11198375 TI - First record of natural infection with Borrelia in ornithodoros (Ornithodoros) savignyi. Reservoir potential and specificity of the tick to Borrelia. AB - Field and laboratory data provided convincing evidence implicating O. savignyi at Shelateen, Halayeb province as a reservoir and a vector of a specific Borrelia. Using direct immunofluorescence Borrelia infection was detected for the first time in a natural population of O. savignyi in Egypt. The overall infection rate (IR) was relatively high (50.63%) and the infected ticks were capable of transmitting the infection to hamsters during feeding. Infected nymphs maintained borrelial infection transstadially to adults and the transstadially infected stages transmitted the spirochetes to hamsters. However, directly infected females were more efficient than males in transmitting the spirochetes to hamster and the IR of hamsters increased gradually by increasing the number of feeding infected ticks upon each hamster. Transovarial transmission of Borrelia intrinsic to O. savignyi occurred during the first and second gonadotrophic cycle of the infected females. The Borrelia sp. detected in the field collected O. savignyi showed specificity for its own natural tick host species when compared with B. crocidurae isolated from O. erraticus. Although the two tick species acquired, transstadially transferred and transmitted the two spirochetal infections, each tick species failed to transovarially transmit Borrelia isolated from the natural population of the other tick species. PMID- 11198376 TI - IL-1, IL-4 production and IgE levels in acute and chronic fasciolosis before and after triclabendazole treatment. AB - IL-1 generation by mononuclear phagocytes, IL-4 production by Th2 lymphocytes and IgE levels in serum were measured in eight patients with acute fasciolosis and seven patients in the chronic stage of the disease before and after triclabendazole treatment. Results were compared with those of a control group of ten individuals. The monocytes and lymphocytes from patients with acute and chronic fasciolosis produced significantly lower levels of IL-1 and IL-4 respectively, particularly in the chronic phase of the disease, as compared to the control. A significant increase in IgE level in both acute and chronic fasciolosis was observed. The level was significantly higher in acute as compared to chronic cases. After treatment with triclabendazole IL-1, IL-4 and IgE levels moved towards the control indicating obvious improvement in the immunological responses of the patients. PMID- 11198377 TI - Effect of niclosamide on the marketable fish Liza ramada (Risso, 1826) concerning accumulation in muscles and activities of three metabolic liver enzymes. AB - The accumulation in muscles and the effect of different concentrations of niclosamide (Bayluscide) on the metabolic enzymes; succinate dehydrogenase (SDH), pyruvate dehydrogenase (PDH) and lactate dehydrogenase (LDH) in the liver of the Thin-lip grey mullet after 1, 2 & 3 weeks were studied. The molluscicide residues were detected in the muscles. The residues increased with the increase of concentrations of niclosamide as well as the time of exposure. On the other hand, LDH showed significant increase. But, SDH and PDH showed significant decrease. No doubt, this disturbance in the three liver enzymes cause disturbance in the process of metabolism. The important point is what about man who consumes a fish with niclosamide accumulated in its muscles. PMID- 11198378 TI - On the schistosomicidal effect of triclabendazole an experimental study. AB - Mice were infected with S. mansoni cercariae and divided to three groups: one as control, the others were treated with a single oral dose of PZQ or TCBZ. The efficacy of the drugs was evaluated on the basis of egg excretion, number, sex and distribution of worms, oogram changes and tissue egg load. Results demonstrated that eggs disappeared from the stools in both treated groups, all worms died in the PZQ treated group while in the TCBZ group, worm production amounted to 84%. Male worms were more susceptible to the two drugs, they died earlier. On the fourth week after TCBZ, the few surviving worms returned back from their hepatic shift to the mesenteric veins. By studying the oogram pattern, it was found that PZQ had a direct lethal effect on the mature eggs; TCBZ had a lower effect on egg viability but the oogram findings indicated cessation of egg laying. PMID- 11198379 TI - Sublethal concentration of Ambrosia maritima(Damsissa) affecting compatibility of Biomphalaria alexandrina snails to infection with Schistosoma mansoni through disturbing the glycolytic pathway. AB - High glycolytic flux as an emergency pathway for generating ATP was recorded as the most important metabolic pathway required for the success of Biomphalaria Schistosome sporocyst interaction. Effect of LC25 of dry powdered Ambrosia maritima (Damsissa) as plant molluscicide on hexokinase (HK), pyruvate kinase(PK), glucose phosphate isomerase(GPI) was tested. It resulted in a significant inhibition of the three investigated enzymes. Treatment of snails with LC10 concentrations of A. maritima reduced considerably the infection rate of Biomphalaria alexandrina with Schistosoma mansoni to be 34% compared to an infection rate of 80% in control non-treated snails. Longer prepatent period and remarkable decrease in cercarial production was also recorded in snails treated with the sublethal concentrations of this molluscicide. PMID- 11198380 TI - DNA sequence polymorphisms in two strains of Fasciola hepatica from Egypt and Europe. AB - A new PCR based system was used that had broad detection capability among parasites based on a conserved region of the 18 S ribosomal DNA gene. Five samples each of European and Egyptian Fasciola hepatica of bovine origin were obtained and DNA was isolated. The target of the PCR primers was a fragment of approximately 600 nucleotides in length corresponding to a region of the 18 S rRNA gene. Sequences were compared over a 107 base pair region that identified polymorphism between the strains. All five Egyptian isolates were identical. Likewise all of the European isolates had identical sequence. There were polymorphisms between the two strains and also with F. hepatica isolates from North America. Both the European and Egyptian isolates have a single base addition in the polymorphic region. In addition there is a single base substitution in the Egyptian isolates when compared to the others. This region is a small target that can be used to identify the origins of different F. hepatica isolates. PMID- 11198381 TI - Effect of vaccination on expression of intracellular adhesion molecules 1 and vascular cell adhesion molecules 1 in murine schistosomiasis. AB - This work studied the approach of vaccination by utilizing ultraviolet attenuated S. mansoni cercariae on two surface adhesion molecules expression, intercellular adhesion molecules 1 (ICAM-1) and vascular cell adhesion molecules 1(VCAM-1). ICAM-1 and VCAM-1 expression were studied in livers of 37 CD-1 female mice (2 months aged and about 30 gm waited) which were divided into 3 groups. Analysis of adhesion molecules expression was done by direct immunofluorescence staining and quantitative measurement of positive signals by image analyzer. The main findings were: (1) ICAM-1 and VCAM-1 expression was mainly localized on granuloma cells. (2) The video count areas that expressed ICAM-1 and VCAM-1 were markedly increased in vaccinated than naive animals. The ICAM-1 intensity was (58.7%) in VC while (31.1%) in NC mice group. (3) Similarly the intensity of VCAM-1 expression was (73%) In VC while (54.2%) in NC. (4) The % change in ICAM-I expression relative to naive mice group was (326.9%) and (704.7) in NC and VC mice group respectively. (5) The % change in VCAM-1 expression in vaccinated animals relative to naive animals was (67,700) and (91,175) in NC and VC mice groups respectively. PMID- 11198382 TI - Potential for Culex pipiens to develop resistance against Bacillus sphaericus toxins. AB - Susceptibility of field Culex pipiens populations to Bacillus sphaericus and the possibility of resistance development in the selected laboratory colony were investigated. 180 populations collected from Giza and Qualyobia over one year show no marked variation at LC50 and LC90 values. Larvae of laboratory colony of Cx pipiens were subjected to selection pressure with a preparation of Bacillus sphaericus strain 2362 at LC80 values for 20 successive generations. The selected laboratory colony began developing resistance at F10 (RR = 1.69) when compared with its unselected counterpart. The magnitude of resistance increased gradually and reached 33 fold by F20. The unselected colony reared without any exposure to the B. sphaericus toxin, did not show any marked change in their susceptibility to this microbial agent. PMID- 11198383 TI - Demodex folliculorum causing pathological lesions in immunocompetent children. AB - Scabies and pediculosis are the vast major ectoparasites infesting man. Demodex folliculorum is unreported ectoparasite, since it is considered harmless. Marked pathologic infestations caused by D. folliculorum were diagnosed in five immunocompetent children, The infestations are successful treated with 2% permethrin cream. PMID- 11198384 TI - Identification of mouth part antigens of Fasciola gigantica and Toxocara vitulorum and its molecular targets recognized by homologous and heterologous adult anti-sera against adult. AB - Sodium dodecyl sulphate poly-acrylamide gel electrophoresis (SDS-PAGE) fractionation of whole-worm and mouth part antigens of F. gigantica and T. vitulorum showed obvious qualitative and quantitative differences. Three different anti-sera, raised in rabbits against adult extracts of F. gigantica, T. vitulorum and Monieza expansa, were utilized in immunoblotting for identification of mouth part antigens that cross-react with adult worm of the same species or of different species. 7 and 8 poly peptides were recognized in F. gigantica and T. vitulorum mouth parts respectively by their homologous rabbits anti-adult anti sera. The cross reactive antigens in F. gigantica which recognized by T. vitulorum anti-sera was 234 KD, while two components of M.wt. 113 and 93 KD were detected by M. expansa serum in the same extract. Furthermore, T. vitulorum antigens which cross-reacted with F. gigantica anti-serum 150 and 65 KD and with M. expansa were 65 and 49 KD. PMID- 11198385 TI - The effects of Nosema algerae Vavra and undeen (Microsporida: Nosematidae) pathogen of Culex pipiens L.(Diptera: Culicidae) from Egypt on fecundity and longevity of the host. AB - A microsporidian, Nosema algerae Vavra and undeen, was found parasitizing larvae and adults of a laboratory colony of Culex pipiens L. originated from Gharbia Governorate. A detailed examination of the developmental stages of the pathogen under light and electron microscopes showed that they are typical of the original characteristics of N. algerae. Other observations on the infected individuals revealed that spores of the pathogen were found in all organs of the infected mosquitoes except the nervous system. The most heavily infected organ was the alimentary canal, particularly the mid gut. The susceptibility of the different larval instars of a laboratory maintained Cx. pipiens colony to infection by N. algerae was determined. Using 24 hours exposure to a range of doses between 40 and 5 x 10(5) spores per cm, larvae of the 1st and 2nd instars were more susceptible to infection than 3rd and 4th instar larvae as indicated by the differences in the estimated IC50 dosages. The dosages of N. algerae which produced 50% mortality (LC50) in each group of treated larvae was approximately 25-30 times higher than the doses that caused 50% infection. When a sublethal dose of 1.2 x 10(3) spores per cm2 of N. algerae was used to induce infection in each of the different larval instars infection rates of 100% were obtained in all exposed larval instars and in adults developed from them. Females from larvae infected with N. algerae had significantly reduced fecundity, fertility, and longevity regardless the larval instar in which infection was initiated. However, the reduction was obviously high when 1st and 2nd instars were exposed. The accumulative effects of reduced survival and fecundity on the reproductive potential of the infected females derived from larvae that were infected as 1st and 2nd instars probably serve to limit the natural increase of mosquito populations. Further studies are necessary, however, to determine the efficacy of this pathogen on target species in the natural environment where the combined effect of the pathogen and environmental stresses may enhance its pathogenicity. PMID- 11198386 TI - Study of protein profile in the visceral leishmaniasis. AB - A study of the ten proteins of the protein profile in 7 children infected with visceral leishmaniasis leads to obtain an evocating diagram of the protein profile in this disease. In these patients, the authors have found the association of a polyconal hypergammaglobulinaemia, an inflammatory syndrom (increase of orosomucoid, CRP, alpha-1-antitrypsin, decrease of albumin, prealbumin and transferrin), and an haemolytic syndrom (decrease of haptoglobin). Such a diagram may be an supplementary help to establish the diagnosis of visceral leishmaniasis, in some cases when it is difficult to find the parasites. PMID- 11198387 TI - Seasonal infestation of Oestrus ovis larvae in sheep heads in central region of Saudi Arabia. AB - During a period of 12 months, 544 sheep heads were examined for infestation with Oestrus ovis larvae in Riyadh abattoir, Central Region of Saudi Arabia. The tested animals were males, less than one year old. The prevalence of infestation was 5.9%. The peak of infestation reached 23.3% in March 2000. The highest mean number of larva per infested sheep head in first, second and third instars larvae were 5, 7, and 5.3 respectively in spring months. A total for all instars being 4.3 larva per sheep head. All three stages disappeared in summer and winter months probably due to the very hot and dry weather. PMID- 11198388 TI - Schistosoma mansoni egg specific antibodies and circulating antigens: assessment of their validity in immunodiagnosis of schistosomiasis. AB - A total of 127 individuals of different age and sex; 92 from Kafr-Sendewa, Qualyobia Governorate, Egypt, in comparison to 23 cases with hydatidosis and fascioliasis as a parasitic control group, and 12 healthy control group from non endemic area. All cases were screened by clinical examination, urine, stool, rectal snip, abdominal ultrasonographic examination and indirect haemagglutination test (IHAT). Accordingly, they were grouped into active intestinal schistosomiasis group, seropositive group by (IHAT), normal control group from the same endemic area, parasitic control group and normal control group. All cases were subjected to detection of IgG, IgM, IgG4, anti-soluble egg antigen (SEA) and anti-excretory-secretory egg antigen (ESEA) by ELISA tests; and circulating egg antigens by double-sandwich ELISA techniques. The results showed that IgG4 anti-SEA is the best diagnostic test, as it gave the best diagnostic efficacy (90%). Also, it is a good screening test which can be used in endemic area as it gave significant difference between the active intestinal schistosomiasis cases with each of the endemic control group (P < 0.001) and the seropositive cases (P < 0.05). Other valid diagnostic egg specific antibodies tests were IgM anti-SEA and IgG anti-SEA as their diagnostic efficacy were 80% and 76.6% respectively (P < 0.05). The diagnostic efficacy of circulating antigen detection (C.Ag) test was 70% (P < 0.05). In addition, it was the most specific test with 100% specificity. IG4-anti-ESEA gave the least cross-reaction with other parasites (17.3%). The mean optical density (OD) level of circulating antigen detection test was significantly higher in the organomegalic (hepatosplenomegaly) cases than the non-organomegalic cases (P < 0.05). PMID- 11198389 TI - The immunological responses in relation to egg extrusion rate and pathological changes in Schistosoma haematobium patients. AB - A total of 30 males with proven S. haematobium infection were subjected to egg count, serological estimation of serum levels of soluble egg antigens and its specific antibody "SEA IgG" and cystoscopic examination of lower urinary tract. Correlation between the pathological changes and number of living extruded eggs showed negative insignificant correlation. However, the relation between the pathological changes and anti-SEA IgG showed positive insignificant correlation. PMID- 11198390 TI - Bioactivity of Anagallis arvensis and Calendula micrantha plants, treated with ammonium nitrate, superphosphate and potassium sulphate fertilizers, on Biomphalaria alexandrina. AB - The survival rate of B. alexandrina snails maintained in aqueous solutions of the two tested plants (Calendula micrantha and Anagallis arvensis) decreased gradually with time until the 9th week and 10th week where the survival rate was zero in the high concentration of A. arvensis and C. micrantha, respectively, meanwhile, the survival rate of the control was 20%. Also, the two plants caused reduction in hatchability of snails egg masses. Thus, the percent of hatching in A. arvensis (82 ppm) was 46% and in C. micrantha was 72% compared with control (97.29%). Both plants reduced the infection rate of Biomphalaria alexandrina snails with Schistosoma mansoni miracidia to 41.17% and 61.9%, respectively, compared with control (90%). C. micrantha caused much higher reduction in snail infection rate than A. arvensis. The prepatent period was significantly prolonged in snails maintained at higher concentration of both plants. The cercarial output (expressed as mean number/snail) revealed that, A. arevensis caused a significant reduction in cercarial production than control. While, high concentration (120 ppm) of C. micrantha caused a significant elevation in the mean number of cercariae/snail. However, the total number of cercariae produced by all snails in each group showed a reverse relation with the tested concentrations in both plants. PMID- 11198391 TI - The pathogenesis of arthropathy in experimental Schistosomiasis mansoni. AB - The pathogenesis of arthropathy in experimental schistosomiasis mansoni was studied. 70 Swiss albino mice were used, 14 served as control while 56 were subcutaneously infected with 80-100 Schistosoma mansoni cercariae/mouse. Mice were sacrificed at 8, 10, 12, 14, 16, 18 and 20 weeks postinfection (p.i.). Shoulder and knee joints were taken and processed for H & E stain and immunoperoxidase stain. As regards histopathological examination, 75% of infected mice showed marked pathological joint changes, with no Schistosoma ova could be detected in all examined sections. These changes appeared at the 12th week (p.i) and became more severe with the chronicity of infection. Immunohistochemical examination of the infected joints, revealed 75% positivity of schistosomal antigen deposition with mild to moderate expression (in early and late stages of infection respectively). The detection of schistosomal antigen in joints of infected mice which coincided with the histopathological affection, can be considered as the aetiological agent in induction of schistosomal arthropathy. Hence, the term reactive schistosomal arthropathy can be changed into schistosomal arthritis. PMID- 11198392 TI - Stapling procedure for hemorrhoids versus conventional haemorrhoidectomy. AB - Forty patients admitted at the Saudi German Hospital were randomly assigned to Milligan-Morgan haemorrhoidectomy (n = 20) or the circular stapled procedure. Under general anesthesia patients underwent standardized haemorrhoidectomy or had a circumferential doughnut of rectal mucosa and submucosa above the dentate line excised and closed with a standard circular end to end stapling device. All patients received the same preoperative and postoperative analgesic and laxative regimens. Patients completed linear analogue pain charts each day and were interviewed at 1, 3, and 12 weeks postoperatively. Summary measures of average pain experience were calculated from 10 cm linear analogue pain scores and were used as the primary outcome measure. The stapled group was found to have shorter anesthesia time (9-25 minutes, median 18) versus (15-35 minutes, median 22). Average pain in the stapled group was significantly lower than it was in the Milligan-Morgan group (0.2-7.6, median 2.1) versus (3.1-8.5, median 6.5). Hospital stay and time to first bowel motion were not significantly different between both groups. Return to normal activity was significantly shorter in the stapled group (3-60 days, median 17) versus (14-90 days, median 34). Early and late complications, patient assessed symptom control, and functional outcome appear to be similar after short term follow up. PMID- 11198393 TI - A case report of human coenurus cerebralis in Tanta, Egypt. PMID- 11198394 TI - Detection of cytomegalovirus in urine of hearing-impaired and mentally retarded children by PCR and cell culture. AB - This study was carried out to determine the prevalence of cytomegalovirus (CMV) excretion in urine among 30 deaf children and 91 mentally retarded children by cell culture and PCR. As a control, urine samples from 121 children without hearing disability or mental retardation were also tested. The study revealed that 15 of 30 (50%) deaf children and 16 of 91 (17.6%) mentally retarded children were excreting CMV in their urine. Among the control group we observed that only 2 of the 121 (1.8%) children were CMV excretors. As CMV excretion in urine is generally considered to indicate a congenital infection, it is very likely that congenital CMV is highly incriminated in mental retardation and deafness among children in Mauritius. PMID- 11198395 TI - Glucose transport in cerebral microvessels during Plasmodium yoelii nigeriensis infection in mice. AB - Plasmodium yoelii infected cerebral micro vessels of mice registered a significant increase in D-[U-14C] Glucose transport as compared to normal microvessels which was found to be time, temperature and concentration dependent. Metabolic inhibitors galactose, manose, 2-deoxy glucose and D-glucose showed noticeable inhibition of the same. PMID- 11198396 TI - Relevance of direct agglutination test in seroepidemiological survey of Kala-azar in epidemic foci of Bihar. AB - The performance of direct agglutination test (DAT) was evaluated under field conditions in three endemic districts of Bihar. In three villages of these districts, 197 households were surveyed with a population of 1167 individuals. Out of 1167 individuals, 603 were clinically examined for VL and blood samples of each examined individual were collected for DAT. The proportion of DAT positivity in both males (32.33%) and females (32.94%) was statistically not significant (p > 0.05). The proportion of DAT positivity in all age groups was observed to be similar (p > 0.05). The GMRT was observed highest in active VL cases. Out of 20 DAT positive individuals having fever, 5 were examined parasitologically (bone marrow aspiration) and in three cases positivity was observed. This showed the relevance of DAT in early diagnosis of visceral leishmaniasis and usefulness of DAT in field conditions. PMID- 11198397 TI - Serological investigation of malaria outbreak in Thar desert of Rajasthan. AB - A serological investigation by a repeat cross-sectional survey was conducted in Thar desert (Rajasthan) during and after one year of malaria outbreak to determine malaria endemicity using ELISA as a tool. The assay was based on indirect ELISA to measure antibody levels against a nonapeptide R1 (EENVEHDA-cys) derived from Pf 155/Resa and Plasmodium falciparum crude antigen. Finger prick blood samples were collected from individuals belonging to all age groups. Sera were tested at already standardized optimum dilution to detect antigen specific immunoglobulin isotype. The mean ELISA O.D. values 0.153 for anti R1 peptide and 0.162 for anti Pf antigen reflected the seronegative profile, when the focal malaria outbreak occurred in 1994. A substantial increase in antibody levels was detected in individuals after one year showing mean ELISA values for anti-R1 and anti-Pf antigens as 0.52 and 0.58 and seropositivity as 75.2% and 52% respectively. Data obtained from the present study indicate that serological survey could be done to assess the situation in case of reappearing or disappearing status of malaria in a defined population. PMID- 11198398 TI - Role of macrophages in experimental malaria: VII--studies on adoptive transfer of macrophages. AB - Adoptive transfer of purified macrophages harvested from normal, Plasmodium berghei infected and latent/cured mice and also macrophages exposed to parasites in vitro were carried out to see the role of macrophages in transferring immunity against P. berghei infection. Macrophages obtained from mice having high parasitaemia at a dose of one million cells/animal showed significant increase in survival period (SP) and K values, compared to controls. Macrophages exposed to low parasite density conferred significant K values only. There was a decrease in prepatent period (PP) in the animal which received macrophages from animals cured 7-11 months compared to controls. The adoptive transfer studies with macrophages conditioned in vitro to parasite contributed towards increased protection of host against P. berghei as expressed by K values only. These studies showed that the macrophages harvested from infected mice were capable of acting as immunogen against P. berghei infection. PMID- 11198399 TI - Efficacy of chloroquine in febrile Plasmodium falciparum infected children in Mewat region of Haryana. AB - During 1996, Mewat region of Gurgaon district in Haryana experienced high incidence of Plasmodium falciparum malaria, assuming epidemic proportion in large number of villages affected by floods. Mortality due to fever was also high. In vivo 7 days study amongst 32 febrile P. falciparum infected children of 1 to 14 years age group in flood affected villages of Ferozpur Jhirka Community Health Centre of Mewat region was carried out. All the 32 cases showed good response to chloroquine suggesting that drug was effective and useful as first line of treatment, reducing severity of P. falciparum infection and resolving fever due to infection of the species. The study also indicated that chloroquine was an effective drug in controlling epidemic situation and mortality in areas of high incidence of P. falciparum. Pyrogenic stimulus was variable among different developmental stages of P. falciparum and suggestive of the need of earliest possible initiation of anti-malaria treatment, community based fever survey and blood smear examination. Increase in incidence of fever in an endemic community, particularly in children, should be considered as an indicator of impending outbreak of P. falciparum malaria. Effectiveness of diagnostic and control measures taken can be evaluated on the basis of incidence of malaria particularly due to P. falciparum infection and also incidence of fever in an endemic community. PMID- 11198400 TI - A preliminary field study on repellency of neem oil against Anopheles dirus (Diptera:Culicidae) in Assam. PMID- 11198401 TI - Plasmodium malariae--a case of quartan malaria in Assam. PMID- 11198402 TI - Implementation of revised strategy of filaria control-baseline clinico parasitological survey. AB - A clinico-epidemiological study of filariasis was carried out in Varanasi District in October and November, 1997 to generate baseline data for assessing the impact of Mass Drug Administration (MDA) in the district. Disease rate was found to be 6.6% (9.9% in males and 3.0% in females) and microfilaria rate was 5.3% (5.2% in males and 5.5% in females). Mean microfilaria density was found to be 9.86 per 20 Cu.mm blood. Genital manifestations (77.5%) outnumbered all other forms of clinical manifestations. Vector infectivity rate was found to be 0.93%. PMID- 11198403 TI - Occurrence of asymptomatic microscopic haematuria in a filarial endemic area of Orissa, India. AB - To determine the frequency of occurrence of asymptomatic microscopic haematuria in filarial endemic area of Orissa, where the mf rate and disease rate were observed to be 14.8% and 37.2% respectively, clinical examination, night blood smear examination, morning midstream urine examination were conducted on 697 persons-randomly selected from all age groups in 8 villages of Puri tehsil. Out of them, 15.6% were found to have asymptomatic haematuria (Grade I-14.7%, Grade II-0.6%, Grade-III 0.3%). The prevalence of asymptomatic microscopic haematuria was observed to have positive statistical correlation with mf status (P < 0.001), filarial antigenaemia (Ag) (P < 0.001), antibody (Ab) (P < 0.001) and circulating immunocomplex antigen (CIC-Ag) (P < 0.001). The prevalence was also found to be increased with the progression of the disease process i.e. from endemic normal to chronic manifestations. None of the cases having Grade-II and III haematuria cases revealed any gross renal pathological lesions, when subjected to special investigations like X-ray, IVP, cystoscopy and urethroscopy. PMID- 11198404 TI - Anthropophily of Anophelines in Duars of West Bengal and other regions of India. AB - Attempts have been made to identify the source of blood meals of twenty three anopheline species from various areas of high malaria endemicity in India. Anopheles minimus, Anopheles fluviatilis and Anopheles dirus showed a high propensity for human blood in North-Eastern parts of the country while Anopheles sundicus was found to be anthropophilic in Andaman & Nicobar Islands. Anopheles culicifacies, Anopheles maculatus and Anopheles philippinensis were found primarily zoophilic in north-eastern areas. High anthropophily has been closely related to sporozoite infection in anophelines specially in Anopheles minimus and is of great epidemiological significance. PMID- 11198405 TI - Honing type 2 diabetes treatment. PMID- 11198406 TI - Will I get sick if I accidentally eat moldy bread or cheese? PMID- 11198407 TI - What's the truth about the health risks of sugar substitutes such as saccharin and aspartame? PMID- 11198408 TI - Can you contract the AIDS-causing HIV virus if an infected person sneezes on you? PMID- 11198410 TI - The pros and cons of home testing. PMID- 11198409 TI - Hope for leukemia. PMID- 11198411 TI - Wound, heal thyself. PMID- 11198412 TI - Aspirin for healthy hearts. PMID- 11198413 TI - A more accurate prostate test? PMID- 11198414 TI - New treatment for postherpetic neuralgia. PMID- 11198415 TI - Re-evaluating Down syndrome tests. PMID- 11198416 TI - Migraine: tailored treatment works best. PMID- 11198417 TI - Hip protectors are hip. PMID- 11198418 TI - Don't lose sight of your diet. PMID- 11198419 TI - Proteomics: a link between genomics, genetics and physiology. AB - Thanks to spectacular advances in the techniques for identifying proteins separated by two-dimensional electrophoresis and in methods for large-scale analysis of proteome variations, proteomics is becoming an essential methodology in various fields of plant biology. In the study of pleiotropic effects of mutants and in the analysis of responses to hormones and to environmental changes, the identification of involved metabolic pathways can be deduced from the function of affected proteins. In molecular quantitative genetics, proteomics can be used to map translated genes and loci controlling their expression, which can be used to identify proteins accounting for the variation of complex phenotypic traits. Linking gene expression to cell metabolism on the one hand and to genetic maps on the other, proteomics is a central tool for functional genomics. PMID- 11198420 TI - An osmotin-like cryoprotective protein from the bittersweet nightshade Solanum dulcamara. AB - Cold acclimation in plants is a polygenic phenomenon involving increased expression of several genes. The gene products participate either directly or indirectly towards increasing cold tolerance. Evidence of proteins having a direct effect on cold tolerance is emerging but limited. With isolated protoplasts from warm-grown kale (Brassica oleracea) as a model system, we tested protein fractions from winter bittersweet nightshade, Solanum dulcamara, stems for the presence of proteins that have a cryoprotective effect. Purification of one such fraction resulted in isolation of a 25 kDa protein. N-terminal Edman degradation amino acid sequence analysis showed that it has high homology to osmotin and osmotin-like proteins. When added to warm-grown protoplasts, it increased the cryosurvival of frozen-thawed protoplasts by 24% over untreated or BSA-treated controls at -8 degrees C. A cDNA library which was made in November from stems and leaves of S. dulcamara was successfully screened for the corresponding cDNA clone. The deduced amino acid sequence indicated that the protein consists of 206 amino acid residues including a N-terminal signal sequence and a putative C-terminal propeptide. The mature protein, without the N terminal signal sequence, was expressed in Escherichia coli. The partially purified protein in the supernatant fraction of the culture medium had cryoprotective activity. PMID- 11198421 TI - Amino acid deletions in loop C of the chlorophyll a-binding protein CP47 alter the chloride requirement and/or prevent the assembly of photosystem II. AB - The chlorophyll a-binding protein CP47 directs excitation energy to the reaction center of photosystem II (PSII) during oxygenic photosynthesis and has additional structural and functional roles associated with the PSII water-oxidizing complex. Oligonucleotide-directed mutagenesis was employed to study loop C of CP47 (approximately Trp-162 to Gly-197) which faces the thylakoid lumen. Five short amino acid deletion strains, delta(S169-P171), delta(Y172-G176), delta(G176 P180), delta(E184-A188) and delta(F190-N194), were created that span this domain. The deletion between Gly-176 and Pro-180, located around the middle of loop C, produced an obligate photoheterotroph that could not assemble functional PSII centers. The deletions in mutants delta(S169-P171) and delta(Y172-G176) reduced PSII levels to < or = 20% of the control and thus impaired photoautotrophic growth. In contrast, mutants delta(E184-A188) and delta(F190-N194) were photoautotrophic even though the number of photosystems was decreased by 50%. All PSII complexes assembled in the deletion strains had an increased susceptibility to photoinactivation and deletion of Glu-184 to Ala-188 prevented photoautotrophic growth under chloride-limiting conditions. Furthermore, the removal of the extrinsic PSII-O, PSII-U and PSII-V proteins from mutants delta(E184-A188) and delta(F190-N194) reduced the rates of oxygen evolution and, in the strains lacking either the PSII-O or PSII-V proteins, also increased the photoautotrophic doubling times. These effects were greater in mutant delta(E 184 A188) than in mutant delta(F190-N194) and the order of importance for the removal of the extrinsic proteins was found to be deltaPSII-V > or = deltaPSII-O > deltaPSII-U. PMID- 11198422 TI - Molecular characterization of quinolinate phosphoribosyltransferase (QPRtase) in Nicotiana. AB - Quinolate acid phosphoribosyltransferase (QPRTase), a key enzyme in nicotinamide adenine dinucleotide (NAD) biosynthesis, also plays an important role in ensuring nicotinic acid is available for the synthesis of defensive pyridine alkaloids in Nicotiana species. In this study, cDNAs for QPRTase were characterized from N. rustica and N. tabacum. Deduced proteins from both cDNAs are almost identical and contain a 24 amino acid N-terminal extension, not reported in other QPRTases, that has characteristics of a mitochondrial targeting sequence. In N. tabacum and N. sylvestris, both of which contain nicotine as the major pyridine alkaloid, QPRTase transcript was detected in roots, the site of nicotine synthesis, but not in leaves. QPRTase transcript levels increased markedly in roots of both species 12-24 h after damage to aerial tissues, with a concomitant rise in transcript levels of putrescine N-methyltransferase (PMT), another key enzyme in nicotine biosynthesis. In N. glauca, however, in which anabasine represents the major pyridine alkaloid, QPRTase transcript was detected in both leaf and root tissues. Moreover, wound induction of QPRTase but not PMT was observed in leaf tissues, and not in roots, 12-24 h after wounding. Southern analysis of genomic DNA from the Nicotiana species noted above, and also several others from within the genus, suggested that QPRTase is encoded by a small gene family in all the species investigated. PMID- 11198423 TI - Structure and expression of duplicate AGAMOUS orthologues in poplar. AB - To investigate the homeotic systems underlying floral development in a dioecious tree, and to provide tools for the manipulation of floral development, we have isolated two Populus trichocarpa genes, PTAG1 and PTAG2, homologous to the Arabidopsis floral homeotic gene AGAMOUS (AG). PTAG1 and PTAG2 are located on separate linkage groups, but their non-coding regions are highly similar, consistent with a phylogenetically recent duplication. Intron/exon structure is conserved in relation to AG and the Antirrhinum AG orthologue, PLENA (PLE), and low-stringency Southern analysis demonstrated the absence of additional genes in the poplar genome with significant PTAG1/2 homology. PTAG1 and PTAG2 exhibit an AG-like floral expression pattern, and phylogenetic analysis of the AG subfamily strongly supports evolutionary orthology to C-class organ identity genes. The high degree of similarity shared by PTAG1 and PTAG2 in both sequence (89% amino acid identity) and expression indicates that they are unlikely to be functionally associated with specification of tree gender. Unexpectedly, PTAG transcripts were consistently detected in vegetative tissues. PMID- 11198424 TI - Molecular cloning and characterization of OsPSK, a gene encoding a precursor for phytosulfokine-alpha, required for rice cell proliferation. AB - We previously characterized an OsPSK cDNA encoding a precursor of phytosulfokine alpha (PSK-alpha), a peptide plant growth factor. Southern blot analysis suggested that OsPSK is a single-copy gene in rice, which we have isolated and characterized. The OsPSK gene consists of one large intron and two exons. The 5 amino acid PSK-alpha sequence located close to the COOH-terminus of the precursor is encoded in the second exon. A putative TATA box was found at position -68 with respect to the transcription initiation site. Upstream of this sequence, several potential regulatory elements, including one CAAT-box, three CCAAT-boxes, one enhancer core-like sequence, and three E-boxes could be identified. By constructing plasmids with various lengths of the 5'-upstream regions of the OsPSK gene fused to the coding sequence for bacterial beta-glucuronidase (GUS), we demonstrated a region 1.9 kb upstream of the transcription initiation point, which contains most of the putative 5'-regulatory elements, to be sufficient for maximal-level GUS expression in transformed rice Oc cells. The promoter of the OsPSK gene gave significantly higher levels of GUS expression than the CaMV 35S promoter. These results suggest that the OsPSK promoter could be useful for the constitutive expression of a foreign gene at high levels in transformed rice culture cells. Northern blot analyses suggest that the expression of OsPSK is reinforced by auxin and cytokinin. PMID- 11198425 TI - Circadian and senescence-enhanced expression of a tobacco cysteine protease gene. AB - A cDNA clone encoding a cysteine protease was isolated from a tobacco cDNA library, utilizing as a probe a PCR fragment obtained from degenerated primers based on the conserved sequences of plant cysteine protease genes. A putative protein encoded by the clone NTCP-23 had an amino acid sequence with significant similarities to those of plant senescence-associated cysteine proteases and mammalian cathepsin H. Northern blot analysis showed that NTCP-23 mRNA is expressed in all organs and the mRNA and protein expression is enhanced during natural senescence. We propose that NTCP-23 is responsible for amino acid remobilization especially in senescencing leaves. Furthermore, it was found that the mRNA expression follows a circadian rhythm and is reduced by continuous darkness, wounding and hypersensitive reaction (HR). NTCP-23 is the first cysteine protease whose mRNA expression has been shown to be temporarily reduced by wounding. PMID- 11198426 TI - Characterization of carrot nuclear proteins that exhibit specific binding affinity towards conventional and non-conventional DNA methylation. AB - DNA methylation is associated with transcriptional silencing in vertebrates and plants. In mammals, the effects of methylation are mediated by a family of methyl CpG-binding proteins. In plants the mechanisms by which methylation represses transcription are still not clear. In this paper we describe protein factors in carrot nuclear extracts exhibiting specific affinities for conventional or non conventional methylation acceptor sites. We characterized two classes of proteins: the first, dcMBPI (Daucus carota methylated DNA-binding protein 1), shows high affinity for sequences containing 5-methylcytosine; the second, dcMBP2 (Daucus carota methylated DNA-binding protein 2), efficiently complexes sequences containing 5-methylcytosine in both CpXpX and CpXpG trinucleotides and shows much lower affinity for 5-methyl CpG dinucleotides. Both dcMBP1 and dcMBP2 are abundant proteins differing in molecular weight and binding features. Their activities are modulated during carrot vegetative cell growth and somatic embryo development. This is the first time that, in either plants or mammals, proteins exhibiting specific binding affinities for conventional or non-conventional DNA methylation have been shown. Based on these results, the possibility that both the extent and the context of the methylation might contribute to modulate gene expression is discussed. PMID- 11198427 TI - A Catharanthus roseus BPF-1 homologue interacts with an elicitor-responsive region of the secondary metabolite biosynthetic gene Str and is induced by elicitor via a JA-independent signal transduction pathway. AB - Plants respond to pathogen attack by induction of various defence responses, including the biosynthesis of protective secondary metabolites. In Catharanthus roseus, the elicitor-induced expression of the terpenoid indole alkaloid biosynthetic gene Strictosidine synthase (Str) is mediated via the plant stress hormonejasmonate. In the promoters of several defence-related genes, cis-acting elements have been identified that are important for transcriptional regulation upon stress signals. Here we show that an upstream region in the Str promoter confers responsiveness to partially purified yeast elicitor and jasmonate. Yeast one-hybrid screening with this element as a bait identified a MYB-like protein, which shows high homology to parsley box P-binding factor-1 (PcBPF-1). In vitro analyses showed that the Str promoter fragment contained a novel binding site for BPF-1-like proteins with higher binding affinity than the previously described box P. CrBPF-1 mRNA accumulated rapidly in elicitor-treated C. roseus suspension cells, whereas no induction was observed with jasmonate. Inhibitor studies indicated that CrBPF-1 plays a role in an elicitor-responsive but jasmonate independent signal transduction pathway, acting downstream of protein phosphorylation and calcium influx. PMID- 11198428 TI - Hexose transporters of tomato: molecular cloning, expression analysis and functional characterization. AB - A full-length (LeHT2) and two partial (LeHT1 and LeHT3) cDNA clones, encoding hexose transporters, were isolated from tomato (Lycopersicon esculentum) fruit and flower cDNA libraries. Southern blot analysis confirmed the presence of a gene family of hexose transporters in tomato consisting of at least three members. The full-length cDNA (LeHT2) encodes a protein of 523 amino acids, with a calculated molecular mass of 57.6 kDa. The predicted protein has 12 putative membrane-spanning domains and belongs to the Major Facilitator Superfamily of membrane carriers. The three clones encode polypeptides that are homologous to other plant monosaccharide transporters and contain conserved amino acid motifs characteristic of this superfamily. Expression of the three genes in different organs of tomato was investigated by quantitative PCR. LeHT1 and LeHT3 are expressed predominantly in sink tissues, with both genes showing highest expression in young fruit and root tips. LeHT2 is expressed at relatively high levels in source leaves and certain sink tissues such as flowers. LeHT2 was functionally expressed in a hexose transport-deficient mutant (RE700A) of Saccharomyces cerevisiae. LeHT2-dependent transport of glucose in RE700A exhibited properties consistent with the operation of an energy-coupled transporter and probably a H+/hexose symporter. The Km of the symporter for glucose is 45 microM. PMID- 11198429 TI - Limitations in the use of ozone to disinfect maple sap. AB - The sap of the maple sugar tree (Acer saccharum) contains 2 to 3% sucrose and is traditionally collected early in the year and concentrated by boiling to produce maple syrup. High levels of microorganisms in the sap occur during holding, leading to a darker syrup with lower economic value. We investigated the use of dissolved ozone as a method to reduce the microbial population in sap. After 40 min of ozone treatment, concentrations of up to 0.30 mg/liter were achieved but were ineffective in reducing the aerobic plate count. Three predominant colonies on nutrient agar were selected for isolation and identification from sap. These included one mucoid and one nonmucoid yeast, both identified as Candida, and Pseudomonas fluorescens. When suspended in buffer, each was readily inactivated by ozone. Addition of 3% sucrose to the buffer markedly reduced the effectiveness of ozone. With the use of an ozone generator with a larger ozone output, saturating ozone concentrations (1 mg/liter) were achieved within 5 min but were accompanied by only a 1-log reduction in aerobic plate count of maple sap. After 40 min of ozone treatment, a less than 3-log reduction occurred. The results indicate that, because of the presence of sucrose, ozone may be of limited use in reducing the microbial population in sap. PMID- 11198430 TI - Facilitation of cleaning of alumina surfaces fouled with heat-treated bovine serum albumin by ozone treatment. AB - Facilitation of cleaning of alumina (A12O3) particles fouled with heat-treated bovine serum albumin (BSA), which contains sulfhydryl groups on the molecule, by gaseous ozone was studied. With increasing temperature of heat treatment, the amount of adsorbed BSA onto A12O3 surfaces increased, whereas the rate of BSA desorption during alkali cleaning decreased markedly, resulting in the larger amounts of BSA remaining on 12O3 surfaces. No significant amounts of BSA were removed from A12O3 surfaces by alkali cleaning alone when treated at temperatures above 120 degrees C. Before alkali cleaning, the heat-treated, BSA-fouled AI2O3 at 150 degrees C were treated with 0.05 to 0.30% (vol/vol) gaseous ozone at room temperature. Ozone pretreatment markedly accelerated the rate of BSA desorption during subsequent alkali cleaning. The effect of ozone pretreatment on BSA removal depended on the concentration of ozone and treatment time and hence on the total amount of ozone supplied. The molecular weight (MW) of desorbed BSA during alkali cleaning without ozone pretreatment coincided with the MW of the native BSA, whereas the MW of desorbed BSA during the combined ozone-alkali cleaning was lower than the MW of the native BSA. This indicated that the heat treated BSA molecules adsorbed on A12O3 were partially decomposed into some fragments by ozone pretreatment, resulting in the facilitation of the removal of BSA during alkali cleaning. PMID- 11198431 TI - Bactericidal effects of negative air ions on airborne and surface Salmonella enteritidis from an artificially generated aerosol. AB - The bactericidal effect of high levels of negative ions was studied using a custom-built electrostatic space charge device. To investigate whether the ion enriched air exerted a bactericidal effect, an aerosol containing Salmonella Enteritidis (SE) was pumped into a sealed plastic chamber. Plates of XLT4 agar were attached to the walls, top, and bottom of the chamber and exposed to the aerosol for 3 h with and without the ionizer treatment. The plates were then removed from the chamber, incubated at 37 degrees C for 24 h, and colonies were counted. An average of greater than 10(3) CFU/plate were observed on plates exposed to the aerosol without the ionizer treatment (control) compared with an average of less than 53 CFU/plate on the ionizer-treated plates. In another series of experiments, the SE aerosol was pumped for 3 h into an empty chamber containing only the ionizer and allowed to collect on the internal surfaces. The inside surfaces of the chamber were then rinsed with 100 ml phosphate-buffered saline that was then plated onto XLT4 plates. While the rinse from the control chamber contained colony counts greater than 400 CFU/ml of wash, no colonies were found in the rinse from the ionizer-treatment chamber. These results indicate that high levels of negative air ions can have a significant impact on the airborne microbial load, and that most of this effect is through direct killing of the organisms. This technology, which also causes significant reduction in airborne dust, has already been successfully applied for poultry hatching cabinets and caged layer rooms. Other potential applications include any enclosed space such as food processing areas, medical institutions, the workplace, and the home, where reduction of airborne and surface pathogens is desired. PMID- 11198432 TI - Identification of bovine-specific DNA in feedstuffs. AB - Considering the menace of transmission of bovine spongiform encephalopathy, feed components intended for cattle nutrition must be checked for the presence of bovine-derived materials. We have been using a method based on polymerase chain reaction for the identification of bovine-specific mitochondrial DNA sequences for this purpose. The specificity of the primers for polymerase chain reaction has been tested using samples of DNA of other vertebrate species, which may also be present in rendering plant products. The method allows the detection in concentrate mixtures of 0.125% of bovine-derived material. Bovine DNA at concentrations corresponding to less than 0.5% of bovine-derived material was detected in 3 of the 30 samples of concentrate mixtures collected from distributors' stores all over the Czech Republic. All 44 samples of fish meal collected from the same sources were free of bovine-derived material. PMID- 11198433 TI - Salmonella in the lairage of pig slaughterhouses. AB - The purpose of this study was to determine if lairages of pig slaughterhouses can act as a source of contamination of slaughtered pigs with Salmonella. The prevalence and variety of serotypes of Salmonella in the lairages of two pig slaughterhouses were determined, and the efficacy of the usual cleaning and disinfection on the presence of Salmonella was estimated. Lairages of two pig slaughterhouses were sampled three times when pigs were present. Furthermore, these lairages were sampled after the usual cleaning and disinfection, whereas the lairage of one slaughterhouse was sampled an additional time after improved cleaning and disinfection. Samples were collected by swabbing floor and wall surfaces and collecting the residing fluids on the floor throughout the lairage. Salmonella was isolated in 70 to 90% of the samples when pigs were present. The usual cleaning and disinfection reduced the level of contamination with Salmonella to 25% positive samples, whereas improved cleaning and disinfection reduced this level to 10% positive samples. It is concluded that the waiting period in the lairage of at least 2 h contains a substantial risk for slaughter pigs to become infected with Salmonella, especially for pigs originating from Salmonella-free herds. The usual cleaning and disinfection of the lairage were not sufficient to eliminate this risk, whereas an improved procedure for cleaning and disinfection still was unsatisfactory. PMID- 11198434 TI - Dietary strategies to counteract the effects of mycotoxins: a review. AB - We reviewed various dietary strategies to contain the toxic effects of mycotoxins using antioxidant compounds (selenium, vitamins, provitamins), food components (phenolic compounds, coumarin, chlorophyll and its derivatives, fructose, aspartame), medicinal herbs and plant extracts, and mineral and biological binding agents (hydrated sodium calcium aluminosilicate, bentonites, zeolites, activated carbons, bacteria, and yeast). Available data are primarily from in vitro studies and mainly focus on aflatoxin B1, whereas much less information is available about other mycotoxins. Compounds with antioxidant properties are potentially very efficacious because of their ability to act as superoxide anion scavengers. Interesting results have been obtained by food components contained in coffee, strawberries, tea, pepper, grapes, turmeric, Fava tonka, garlic, cabbage, and onions. Additionally, some medicinal herbs and plant extracts could potentially provide protection against aflatoxin B1 and fumonisin B1. Activated carbons, hydrated sodium calcium aluminosilicate, and bacteria seem to effectively act as binders. We conclude that dietary strategies are the most promising approach to the problem, considering their limited or nil interference in the food production process. Nevertheless, a great research effort is necessary to verify the in vivo detoxification ability of the purposed agents, their mode of action, possible long-term drawbacks of these detoxification decontamination procedures, and their economical and technical feasibility. PMID- 11198435 TI - Inhibition of in vitro Salmonella Typhimurium colonization in porcine cecal bacteria continuous-flow competitive exclusion culturest. AB - Continuous-flow (CF) chemostate cultures were used as models to determine the potential usefulness of undefined porcine cecal bacteria as competitive exclusion (CE) cultures against colonization by Salmonella Typhimurium. One culture, pCF1, was derived from cecal bacteria of an animal maintained on antibiotic-free feed, while the other culture, pCF4, was derived from cecal bacteria of an animal maintained on feed containing chlortetracycline. The effectiveness against a chlortetracycline-resistant Salmonella Typhimurium was examined in CF cultures maintained in the absence (pCF1 and pCF4) and presence (cpCFl and cpCF4) of chlortetracycline. CF cultures were inoculated with each of 10(2), 10(4), and 10(6) Salmonella Typhimurium CFU/ml. Chemostat inocula of 10(2) Salmonella CFU/ml resulted in no Salmonella Typhimurium being detected at 2 and 3 days postinoculation in pCF1 and pCF4, respectively, and after 2 days in both cpCF1 and cpCF4. Inoculations of 10(4) Salmonella Typhimurium CFU/ml resulted in clearance from pCF1 and pCF4 within 4 days and within 3 days from cpCF1 and cpCF4. Following inoculation with 10(6) CFU/ml, no Salmonella Typhimurium were detected in all CF cultures by 6 days postinoculation. The results indicated that in vitro CF cultures of porcine cecal bacteria were able to inhibit the growth of Salmonella Typhimurium. The ability to limit Salmonella Typhimurium growth was not restricted by prior exposure of the cecal bacteria to the feed additive chlortetracycline. The present study demonstrates the potential application of CF cultures as models to aid in the identification of CE cultures against salmonellosis in pigs. PMID- 11198436 TI - Survival and growth of Salmonella and Listeria in the chicken breast patties subjected to time and temperature abuse under varying conditions. AB - Chicken breast patties were inoculated with a mixture of Salmonella Senftenberg, Salmonella Typhimurium, Salmonella Heidelberg, Salmonella Mission, Salmonella Montevideo, Salmonella California, and Listeria innocua. The initial inoculation of bacteria was approximately 10(7) log10 CFU/g. The inoculated patties were processed in a pilot-scale air convection oven at an air temperature of 177 degrees C, an air velocity of 9.9 m3/min, and a low (a wet bulb temperature of 48 degrees C) or high (a wet bulb temperature of 93 degrees C) humidity condition. The patties were processed to a final center temperature of 65 to 75 degrees C. The survivors of Salmonella and Listeria in the processed patties were evaluated. Processing humidity affected the survivors of bacteria. More survivors of Salmonella and Listeria (>2 logs) were obtained for the patties cooked at low humidity than at high humidity. After thermal processing, the patties were stored under air, vacuum, or CO2 at refrigerated (4 degrees C) or thermally abused (8 to 15 degrees C) temperatures. Storage temperature, time, and gas environment affected the bacteria growth. Higher storage temperature and longer storage time correlated to an increased growth of bacteria in the cooked chicken patties. Less Salmonella (2 logs) and Listeria (0.5 to 1 log) cells were obtained in the patties stored under vacuum than in air. Storing the patties in 30% CO2 reduced the growth of Salmonella more than 2 log10 CFU/g. At a CO2 level of 15%, 1 log10 CFU/g of reduction was obtained for Listeria in cooked chicken patties. PMID- 11198437 TI - Fecal shedding of Salmonella spp. by dairy cows on farm and at cull cow markets. AB - As part of a national study of the U.S. dairy cow population, fecal samples were collected from representative cows on 91 dairies and 97 cull dairy cow markets in 19 states. Salmonella spp. were recovered from 5.4% of milk cows, 18.1% of milk cows expected to be culled within 7 days, and 14.9% of culled dairy cows at markets. On a premise basis, Salmonella shedding in milk cows was detected on 21.1% of dairies and 66% of cull dairy cow markets. The percentage of herds with at least one cow with detectable Salmonella fecal shedding was higher during the sampling period from May through July, in herds with at least 100 milk cows, and in herds in the South region. The most common Salmonella serogroups isolated were E (30.8% of isolates) and C1 (28.6%); the most common serotypes isolated were Salmonella Montevideo (21.5% of isolates), Salmonella Cerro (13.3%), and Salmonella Kentucky (8.5%). Fecal shedding of Salmonella Typhimurium or Salmonella Typhimurium var. copenhagen was infrequent (2.8% of isolates). Most isolates (88.9%) were susceptible to all 17 antimicrobials evaluated; multiple resistance was an infrequent occurrence. This study provides information describing the distribution of Salmonella fecal shedding from dairy cows on farm and at markets and will serve as a baseline for future studies. PMID- 11198438 TI - Comparison of different enrichment broths and background flora for detection of heat-injured Listeria monocytogenes in whole milk. AB - Various primary enrichment broths, including University of Vermont medium (UVM), Listeria enrichment broth (LEB), modified LEB, and aerobic and anaerobic L PALCAMY, were compared with aerobic and anaerobic Pennsylvania State University (PSU) broths for the detection of severely heat-injured (62.8 degrees C for 5, 10, or 15 min; no colony appearance after heat injury on aerobic Trypticase soy agar containing 0.6% yeast extract and modified Oxford medium) Listeria monocytogenes Scott A. Anaerobic conditions were produced by adding L-cysteine and then purging the headspace with N2. The effect of uninjured background flora (10(3) CFU/ml of Enterococcus faecium) on frequency of detection was examined. Anaerobic PSU broth resulted in the lowest false-positive rate and the highest frequency of detection of severely heat-injured L. monocytogenes compared with UVM, LEB, and modified LEB (P < 0.05). The presence of E. faecium significantly enhanced the detection of heat-injured (10 min at 62.8 degrees C) L. monocytogenes in aerobic and anaerobic PSU and aerobic and anaerobic L-PALCAMY broths (P < 0.05). The highest concentration of uninjured E. faecium (>10(6) CFU/ml) inhibited the detection of heat-injured L. monocytogenes (P < 0.05). A heat-resistant, LiCl-tolerant Lactobacillus isolate from raw milk increased the rate of both false-positive and false-negative reactions. PMID- 11198439 TI - Surface plasmon resonance analysis of staphylococcal enterotoxin B in food. AB - Surface plasmon resonance (SPR) biosensors are electro-optical instruments used for analyzing real-time protein-protein interactions. This work evaluates an SPR biosensor (Biacore 3000) in the detection of staphylococcal enterotoxin B (SEB) in foods. A sandwich SPR immunosensor involving two antibodies was used. The capturing antibody, bound covalently to the surface of the biosensor chip, performs the initial binding of the antigen and a second antibody binds to the captured antigen. The second antibody makes antigen verification possible and amplifies the signal. Pure SEB as well as SEB in spiked foods (milk and meat) were detected with little interference from the food matrix. In the control experiments with uncontaminated food samples no significant signal was detected. The SPR biosensor assay detects SEB at approximately10 ng/ml rapidly, with initial binding within 2 min. The entire measurement cycle (including washing and chip regeneration) may take 5 min using one antibody or 8 min using two antibodies. These results suggest that the SPR biosensor may be a useful tool for real-time analysis of toxin in foods. PMID- 11198440 TI - Evaluation of a selective broth for detection of Staphylococcus aureus using impedance microbiology. AB - Experiments were conducted to evaluate a selective nutrient broth containing acriflavine and nalidixic acid for detection of Staphylococcus aureus using an impedance microbiological method. Nine species of bacteria, other than S. aureus, were evaluated using the selective broth to determine if these species could be inhibited. A total of 10 ppm of nalidixic acid inhibited the gram-negative species tested, with the exception of Pseudomonas aeruginosa. Similarly, 10 ppm of acriflavine suppressed the Staphylococcus spp. examined; however, S. aureus retained the ability to proliferate. Nutrient broth solution containing 10 ppm of nalidixic acid and 10 ppm of acriflavine (S. aureus impedance broth [SIB]) inhibited multiplication of most of the bacterial species tested and allowed S. aureus to be detected in an average of 16.4 h. Fresh chicken carcass rinses and cooked chicken rinses were inoculated with Escherichia coli and S. aureus and assayed using SIB in conjunction with impedance. Results demonstrated that S. aureus could be detected in less than 11.5 h, although the presence of E. coli decreased detection times. Additionally, impedance assays were conducted using five different poultry products to evaluate the sensitivity of the broth for detecting S. aureus. S. aureus could be detected on poultry products when present at low levels (10(1) CFU/ml) in less than 24 h. These studies demonstrated that SIB may be used in conjunction with impedance for rapid detection of S. aureus. However, without further modification, this method should not be used for enumeration of S. aureus from samples containing mixed microflora. PMID- 11198441 TI - Modeling the growth boundary of Staphylococcus aureus for risk assessment purposes. AB - Knowing the precise boundary for growth of Staphylococcus aureus is critical for food safety risk assessment, especially in the formulation of safe, shelf-stable foods with intermediate relative humidity (RH) values. To date, most studies and resulting models have led to the presumption that S. aureus is osmotolerant. However, most studies and resulting models have focused on growth kinetics using NaCl as the humectant. In this study, glycerol was used to investigate the effects of a glass-forming nonionic humectant to avoid specific metabolic aspects of membrane ion transport. The experiments were designed to produce a growth boundary model as a tool for risk assessment. The statistical effects and interactions of RH (84 to 95% adjusted by glycerol), initial pH (4.5 to 7.0 adjusted by HC1), and potassium sorbate (0, 500, or 1,000 ppm) or calcium propionate (0, 500, or 1,000 ppm) on the aerobic growth of a five-strain S. aureus cocktail in brain heart infusion broth were explored. Inoculated broths were distributed into microtiter plates and incubated at 37 degrees C over appropriate saturated salt slurries to maintain RH. Growth was monitored by turbidity during a 24-week period. Toxin production was explored by enterotoxin assay. The 1,280 generated data points were analyzed by SAS LIFEREG procedures, which showed all studied parameters significantly affected the growth responses of S. aureus with interactions between RH and pH. The resulting growth/no growth boundary is presented. PMID- 11198442 TI - Lactic acid sprays reduce bacterial pathogens on cold beef carcass surfaces and in subsequently produced ground beef. AB - Organic acids have been shown to be effective in reducing the presence of pathogenic bacteria on hot beef carcass surfaces; however, application for decontaminating chilled carcasses has not been fully evaluated. In this study, a postchill, 30-s lactic acid spray (500 ml of 4% L-lactic acid, 55 degrees C) was applied onto outside rounds that had been contaminated with Escherichia coli O157:H7 and Salmonella Typhimurium, subsequent to prechill hot carcass treatments consisting of water wash alone or water wash followed by a 15-s lactic acid spray (250 ml of 2% L-lactic acid, 55 degrees C). The prechill treatments reduced both pathogens by 3.3 to 3.4 log cycles (water wash alone) to 5.2 log cycles (water wash and lactic acid). In all cases, the postchill acid treatment produced an additional reduction in E. coli O157:H7 of 2.0 to 2.4 log cycles and of 1.6 to 1.9 log cycles for Salmonella Typhimurium. The counts of both pathogens remained significantly lower in ground beef produced from the outside rounds that received prechill and postchill acid spray than from those that received a postchill spray only. These data indicate that organic acid sprays may be successfully applied for pathogen reduction in beef carcass processing after the cooler, especially when combined with prechill treatments. PMID- 11198443 TI - Development of a multiple-step process for the microbial decontamination of beef trim. AB - A multiple-hurdle antimicrobial process for beef trim was developed. The microbial profiles of inoculated lean beef trim tissue (BTL) and fat-covered lean beef trim (BTF) were monitored during prolonged refrigerated storage following the application of successive multiple antimicrobial treatments applied to inoculated beef trim on a processing conveyor belt set at a belt speed of 1 cm/s. Beef trim (meat size approximately 15 by 15 cm) was preinoculated with bovine feces before all treatments that included the following: control, no treatment; water wash at 65 psi for five passes; water plus lactic acid (2% [vol/vol] room temperature lactic acid wash at 30 psi for three passes); combination treatment 1 (water plus 65 degrees C hot water at 30 psi for one pass plus hot air at 510 degrees C for four passes plus lactic acid), combination treatment 2 (water plus hot water at 82 degrees C for one pass plus hot air at 510 degrees C for five passes plus lactic acid), and combination treatment 3 (water plus hot water at 82 degrees C for three passes plus hot air at 510 degrees C for six passes plus lactic acid). The effects of treatments on bacterial populations were monitored by enumerating mesophilic aerobic bacteria (APC), presumptive lactic acid bacteria (PLAB), psychrotrophic bacteria (PCT), coliforms, and Escherichia coli biotype 1 on product stored for up to 7 days at 4 degrees C. In the case of BTL, the numbers of APC, PCT, and PLAB increased during storage at 5 degrees C, whereas the numbers of coliform and E. coli decreased on average by 1.8 log CFU/cm2, then remained constant following the initial reduction. Negligible effects on color quality were observed from multihurdle treatment combination 1. In the case of the BTF, the microbial reductions by treatments were much greater than the reduction on BTL. The pH of treated BTF increased more slowly than the pH of treated BTL, resulting in further reduction of the microflora on BTF. Except for control and water treatments, all sample treatments involving lactic acid resulted in continuously decreasing microbial populations. Based on microbial reduction and quality aspects, it was concluded that successively applied combination antimicrobial treatments for meat trim could offer potential food safety benefits. PMID- 11198444 TI - Quantification and variability analysis of bacterial cross-contamination rates in common food service tasks. AB - This study investigated bacterial transfer rates between hands and other common surfaces involved in food preparation in the kitchen. Nalidixic acid-resistant Enterobacter aerogenes B199A was used as a surrogate microorganism to follow the cross-contamination events. Samples from at least 30 different participants were collected to determine the statistical distribution of each cross-contamination rate and to quantify the natural variability associated with that rate. The transfer rates among hands, foods, and kitchen surfaces were highly variable, being as low as 0.0005% and as high as 100%. A normal distribution was used to describe the variability in the logarithm of the transfer rates. The mean +/- SD of the normal distributions were, in log percent transfer rate, chicken to hand (0.94 +/- 0.68), cutting board to lettuce (0.90 +/- 0.59), spigot to hand (0.36 +/- 0.90), hand to lettuce (-0.12 +/- 1.07), prewashed hand to postwashed hand (i.e., hand washing efficiency) (-0.20 +/- 1.42), and hand to spigot (-0.80 +/- 1.09). Quantifying the cross-contamination risk associated with various steps in the food preparation process can provide a scientific basis for risk management efforts in both home and food service kitchens. PMID- 11198445 TI - The effects of cultivating lactic starter cultures with bacteriocin-producing lactic acid bacteria. AB - The effects of bacteriocins produced by six strains of lactic acid bacteria on 9 mesophilic and 11 thermophilic commercial starter cultures were investigated in mixed cultures of commercial starters with bacteriocin-producing strains in milk. The bacteriocins produced by the test organisms were nisin A, nisin Z, lacticin 481, enterocin AS-48, a novel enterocin, and a novel plantaricin. Mesophilic commercial starters were in most cases tolerant of bacteriocins, with only two of the starters being partially inhibited, one by four and the other by two bacteriocins. The aminopeptidase activities of mesophilic starters were generally low, and only one of the combinations of mesophilic starter-bacteriocin producer gave double the aminopeptidase activity of the starter culture without the bacteriocin producer. Thermophilic commercial starters were more sensitive to bacteriocins than mesophilic starters, with six thermophilic starters being partially inhibited by at least one of the bacteriocins. Their aminopeptidase activities were generally higher than those of the mesophilic starters. The aminopeptidase activities of seven thermophilic starters were increased in the presence of bacteriocins, by factors of up to 9.0 as compared with the corresponding starter cultures alone. Bacteriocin-producing strains may be used as adjunct cultures to mesophilic starters for the inhibition of pathogens in soft and semihard cheeses, because mesophilic starters are rather tolerant of bacteriocins. Bacteriocin producers may also be used as adjunct cultures to thermophilic starters of high aminopeptidase activity, more sensitive to lysis by bacteriocins than mesophilic starters, for the acceleration of ripening in semihard and hard cheeses. PMID- 11198446 TI - Cleanability of soiled stainless steel as studied by atomic force microscopy and time of flight secondary ion mass spectrometry. AB - The hygienic status of food contact surfaces can deteriorate with wear. Effective cleaning regimes must remove any adsorbed organic material as well as microorganisms. Previous work has determined the extent of surface wear occurring on a stainless steel surface within the food industry, and we have reproduced representative samples in vitro. Two surface analytical techniques, atomic force microscopy and time of flight secondary ion mass spectrometry were combined with fluorescence microscopy to give detailed analysis of stainless steel surfaces fouled with starch and milk powder, then cleaned with water either by a spray or brushing method. It was found that the surface cleanability is affected by the cleaning regime and the surface roughness, not only the average vertical roughness but also by the shape of the surface defects, with sharp scratches more difficult to clean than wider surface defects. Spray cleaning with distilled water was found to be a selective method by preferentially removing proteinaceous material more easily than fatty acid ester material. The analytical techniques employed provided information on selective cleanability and surface topography at a hitherto unexplored level, and the information gained may be of value in the design and investigation of novel cleaning regimes and hygienic surfaces. PMID- 11198447 TI - Changes in K value and microorganisms of tilapia fillet during storage at high pressure, normal temperature. AB - This study determined the effect of high-pressure, normal temperature (25 degrees C) storage on tilapia fillets. After pressurization, the fillets were stored at normal condition (1 atm [1 atm = 101.29 kPa] and 25 degrees C) for 12 h to evaluate the changes of microbes and K value. The fillets stored at 2,000 atm for 12 h still kept the K value, a freshness index that represents putrefaction with the value beyond 60%, still below 40%, and the K value of the meat without pressurization was up to 92%. Total plate counts of the fillets stored at below 1,000 atm for 12 h were maintained at the value of 4.7 log CFU/g of meat, which was similar to the initial level. However, the counts were obviously decreased to about 2.0 log CFU/g of meat for the fillets stored at above 2,000 atm. The same effect was obtained for psychrophilic bacteria. Enzymes and microbes reactivated apparently after 12 h of normal condition storage of mild pressurized fillets. The study demonstrates that high-pressure storage can inhibit the putrefaction of tilapia meat but no longer after that. PMID- 11198448 TI - Microbiological survey of retail herbs and spices from Mexican markets. AB - In the present study, 304 samples of herbs and spices (garlic powder, cumin seeds, black pepper, oregano, and bay leaves) widely used in Mexico were analyzed for the presence of Bacillus cereus, Salmonella Typhi, Shigella dysenteriae, Escherichia coli, total and fecal coliforms, total mesophilic aerobic organisms, and fungi. Samples were nonpackaged or packaged in polyethylene bags or glass containers. High levels (10(5) to 10(7) CFU/g) of mesophilic aerobic microorganisms were found in most of the samples of garlic powder, cumin seed, and black pepper. Lower levels (<102 CFU/g) were found in oregano and bay leaves. Total and fecal coliforms counts were dependent on the type of packaging. More than 70% of the polyethylene-packaged samples had less than 10(3) CFU/g of microorganisms. Glass and nonpackaged spices showed lower levels of these microorganisms. B. cereus was present in 32 samples of which most were polyethylene packaged. The other pathogenic bacteria were not detected. Aspergillus niger was detected in 29% of the samples, Rhizopus sp. in 19%, and Penicillum sp. and Cunninghamella in 8%. PMID- 11198449 TI - Psychological risk factors in pregnant inmates. A challenge for nursing. AB - PURPOSE: To explore pregnant prisoners' experiences with childhood violence and substance abuse, their parenting attitudes, and their psychological health. DESIGN: This study used a prospective design to describe incarcerated pregnant women's experiences with childhood violence, substance abuse, parenting attitudes, and psychological health and the relationships among these factors. METHODS: Sixty-three pregnant prisoners in their third trimester were interviewed. Owing to the low literacy of this population, all questions were read to participants to maximize comprehension and reliability. RESULTS: Over 60% of respondents reported experiencing family violence during childhood or adolescence. Almost one-half of the women reported using drugs and alcohol during the past year and in their current pregnancy. Substance-abusing respondents were twice as likely to have been victims of physical abuse. All of the women who had been sexually abused during childhood were substance abusers; women who did not use drugs had no such history. Many women in the study had parenting and child rearing attitudes indicative of risk for poor parenting and abuse. More than 70% of the women reported depressive symptoms above the level considered indicative of clinical depression. Women reported low levels of social support; further, 50% of the women had lost an important relationship within the last year and 80% were not in a relationship with a partner at the time of their interview. CLINICAL IMPLICATIONS: The essential components of caring for pregnant prisoners should include extensive screening for substance abuse as well as history of past and current violence. Pregnant prisoners, with their many risk factors, are a group that could benefit from programs that address substance abuse and violence to decrease mental distress. PMID- 11198450 TI - Minimizing risks associated with peripherally inserted central catheters in the NICU. AB - Peripherally inserted central catheters (PICC lines) provide prolonged venous access, a means of administration of needed medications that would otherwise be irritating to peripheral vessels, and a means of assuring better parenteral nutrition to infants who are unable to tolerate enteral feedings. Not only do these central lines provide life-saving therapy, they are easily inserted, cost effective, and convenient. Although there are many benefits to the use of these catheters, physicians and nurses within the NICU must remain acutely aware of the risks involved with placement of PICC lines so that complications can be minimized. Prevention of sepsis in neonates is always a priority, and several measures can be implemented to reduce this risk, including scrupulous aseptic technique, knowledgeable selection of the insertion site, and consistent daily care. Other complications such as thrombosis, extravascular collection of fluid due to catheter migration or blockage, vessel perforation, and line leakage are all concerns when using this valuable tool in the care of infants. Careful catheter tip placement and conscientious ongoing monitoring can assist in reducing morbidity as well as mortality related to PICC lines. PMID- 11198451 TI - Somebody's grandma and grandpa. Children's responses to contacts with elders. AB - PURPOSE: This article describes the planning, implementation, and evaluation of a program that introduced children into a nursing home. METHOD: A qualitative descriptive design was employed to measure the responses of children to the program. The sample consisted of 61 children, including preschoolers and adolescents. Data were collected from children who participated in the activities (n = 33), and from children who had not participated (n = 28). Content analysis was used to analyze the data. RESULTS: There were no differences in perceptions of preschoolers who participated or did not participate in the nursing home visitation program. In contrast, adolescents who had not participated in the activities with elders described physical infirmities and negative experiences with elders, and talked about smells and boredom. However, adolescent participants in the program demonstrated positive perceptions and descriptions of elders. A favorite activity for all ages was hearing the residents' stories and memories. Adolescent participants reported that their experiences and activities in the program had altered their opinions and beliefs, and they expressed the intent to include elders in their lives in the future. CLINICAL IMPLICATIONS: Because adolescent children exposed to these visits expressed positive perceptions of elders it is prudent to plan larger scale studies with these populations, and also to evaluate the effects of the visits on nursing home residents. PMID- 11198452 TI - Giving birth. Perceptions of Finnish childbearing women. AB - PURPOSE: To describe the lived experience of childbirth with women giving birth in Finland. DESIGN: Phenomenology. METHODS: Twenty Finnish women who had recently given birth were interviewed within 2 weeks following childbirth, sharing their perceptions of meaning of their childbirth experiences. Culturally appropriate strategies for qualitative data collection were employed. Trustworthiness of the data was ensured. RESULTS: The richness and diversity of the childbirth experience emerged from the data. One theme identified was a sense of awe at the creation of a new life within the context of birth as a bittersweet paradox. A strong sense of maternal confidence or self-efficacy was identified, which influenced the women's perception of and management of childbirth pain. Feelings of self-actualization were articulated as Finnish women successfully negotiated a challenging life event. CLINICAL IMPLICATIONS: Perinatal nurses should increase their sensitivity to the socio-cultural context of giving birth by acknowledging women's experiences as legitimate sources of knowledge. PMID- 11198453 TI - Pregnant adolescents and their mothers. A shared experience of teen mothering. AB - PURPOSE: To explore and describe the relationships between African American adolescent mothers and their mothers. DESIGN: A qualitative, descriptive approach was used. METHODS: In-depth, audio-taped interviews, using a semi-structured interview guide with open-ended questions, were conducted with a convenience sample of 12 mother/daughter pairs and three teen mother/mother-figure pairs in a university research area designed for the comfort of the participants. Mothers and daughters were interviewed separately to enhance free expression of their feelings. Participants were recruited through an ongoing study on adolescent motherhood. RESULTS: Four major themes emerged from the analysis. The two symbolic themes were communication between mother and daughter and role change. The two dominant interactive themes were conflict and social isolation. CLINICAL IMPLICATIONS: Nursing assessment of pregnant and parenting teen mothers that includes an assessment of the character of the mother/daughter relationship can be valuable in assisting the pregnant teen toward better health. PMID- 11198454 TI - Sexuality & cystic fibrosis. AB - The life expectancy for a child with Cystic Fibrosis has steadily increased over the past few decades from an average of 8 years in 1970 to 29.5 years in 1998. Nurses who care for this special population need to be open to discussions about the quality of life of these individuals, including sexuality, body image, and self-esteem. Specific information concerning expected body image, fertility, and safe-sex practices is essential. Males will want to know about their reproductive choices, and females will need to have counseling about the decision to become pregnant, including the genetic implications for both themselves and the unborn child. PMID- 11198455 TI - Does breastfeeding reduce risk for breast cancer? A short lesson in evidence based practice. AB - Breastfeeding has been promoted by some healthcare providers and childbirth educators as having a protective effect against breast cancer. In an effort to use the best evidence available for teaching patients, this article was written to summarize the literature about the protective effects of breastfeeding. The studies examined consistently demonstrated a mild to moderate protective effect from breast cancer; however, many variables including age, medication use, smoking, and family history affected the risk. While nurses and childbirth educators are in key positions to disseminate information to women concerning their choice in feeding their newborns and how that choice affects their health in general, it is essential that the information they impart is based on evidence. PMID- 11198456 TI - Print and Internet copyrights: cite them! PMID- 11198457 TI - Legal issues surrounding the use of unlicensed assistive personnel. PMID- 11198458 TI - Journey to family-centered care. PMID- 11198459 TI - Journey to family-centered care. PMID- 11198460 TI - Journey to family-centered care. PMID- 11198461 TI - Journey to family-centered care. PMID- 11198462 TI - . . . and then there were two. PMID- 11198463 TI - Should there be laws mandating seatbelts in all school buses? Writing for the pro position. PMID- 11198464 TI - Should there be laws mandating seatbelts in all school buses? Writing for the con position. PMID- 11198465 TI - [Primary effusion lymphoma and other lymphoproliferative diseases associated with HHV-8]. PMID- 11198466 TI - Pancreatobiliary adenosquamous carcinoma (report of two cases). AB - Adenosquamous carcinomas are rare malignant tumors of the pancreas and periampullary region. We present two cases of pancreatic and periampullary adenosquamous carcinoma with clinicopathologic, histo- and immunohistochemical findings. A 51-year-old and a 48-year-old man presented with right upper quadrant pain of three months duration and jaundice for two weeks. Both cases had an elevation of liver enzymes and CA 19-9. In the first case, computerized tomography showed a 3 cm-mass at the pancreatic head. In the second one, endoscopic retrograde choledocopancreatography (ERCP) revealed a mass at the ampulla Vateri localization. A pancreatoduodenectomy was performed for both cases. Gross pathologic examination displayed a solid, gray-white colored 4 cm tumor at the pancreatic head and a solid, pink-white colored, 2 cm-tumor at the periampullary region bulging into the duodenal lumen. Microscopically, both tumors were composed of solid nests of squamous cells with pearl formation and mucin-containing glandular cells and diagnoses were adenosquamous carcinoma. Furthermore, histo- and immunohistochemical findings were consistent with microscopic diagnoses. PMID- 11198467 TI - [Histopathologic examination of the intervertebral lumbar disk. Evaluation of its usefulness and limitations]. AB - A retrospective clinical-pathological review of 192 lumbar intervertebral discs removed via an interlaminar approach or percutaneous nucleotomy from patients suffering from sciatic pain was carried out in order to assess if routine examination is useful. Only for a case of our series, which showed ill defined features at preoperative neuroradiologic imaging, an intraoperative pathologic examination was necessary. Immunohistochemical study was never required. A routine examination with a hematoxilin-eosin stain was sufficient also to recognize postoperative scar in patients reoperated. In conclusion we think that routine examination of the intervertebral disc is a procedure which is not expensive and useful to assess the nature of the lesion in reoperated patients and in rare cases showing unclear radiologic pattern. PMID- 11198468 TI - [Heterotopic mesenteric ossification. Description of a case]. AB - We describe a case of heterotopic mesenteric ossification presented in a 25 year old male who underwent laparotomy for a fire-gun injury. Two weeks later he experienced small bowel obstruction and for this reason he has been operated five times with removal of segments of small bowel. Now, nine months later, he needs ileostomy to avoid another obstruction. PMID- 11198469 TI - [Guidelines for reporting cutaneous melanocytic lesions]. PMID- 11198470 TI - [Guidelines for reporting cutaneous melanocytic lesions]. PMID- 11198471 TI - Tumour cell hybridization and metastasis revisited. AB - This article reviews a long-standing hypothesis that metastases might be initiated through the generation of hybrids between primary tumour cells and tumour-infiltrating leucocytes such as macrophages. In this concept the hybrids become metastatic through expression of the leucocyte motility phenotype. A history of the hybrid hypothesis is presented along with recent evidence on how macrophage x tumour cell hybridization could account for some of the most defining characteristics of metastatic cells: aneuploidy, enhanced motility, aberrant glycosylation and, particularly seen in melanoma, phenotypic diversity. PMID- 11198472 TI - Partial characterization of an abundant human skin melanosomal 66 kDa protein (MP 66) and investigation to purify a similar protein from B16 murine melanoma tumours. AB - A single polypeptide protein of molecular weight 66kDa (MP 66), purified to homogeneity from melanosomes of normal human cadaver skin epidermal melanocytes, was further characterized. Based on the yield in the present investigation, the intracellular concentration of this protein was calculated to be 4.2 microM. It was shown to be a glycoprotein on gel electrophoresis. Based on its partial N terminal amino acid sequence, it was shown to be distinct from known melanosomal proteins such as gp 75, tyrosinase-related protein-2 (TRP-2) and Pmel 17. Investigation to purify a similar type of protein from B16 murine melanoma tumours by following the same purification procedure resulted in a partially purified protein with a molecular weight of 66 kDa. However, unlike MP 66, this protein did not show inhibition of the monophenolase activity of tyrosinase at pH 6.8. Finally, the effects of 0.5 mM each of CaCl2, ZnSO4 and FeSO4 together, and of human skin epidermal melanosomal proteins, were studied on melanin polymerization at pH 4.7. The metal cations failed to initiate melanin polymerization, while melanosomal proteins did in a dose-dependent manner. PMID- 11198473 TI - Overexpression of nPKCdelta in BL6 murine melanoma cells enhances TGFbeta1 release into the plasma of metastasized animals. AB - Transforming growth factor-beta (TGFbeta) contributes to the promotion of invasion, metastasis, angiogenesis and even immunosuppression. Since overexpression of the delta isoform of protein kinase C (nPKCdelta) in BL6 murine melanoma cells (BL6T cells) increases their metastatic capacity, we investigated the possible involvement of TGFbeta1 in this process. Immunohistochemical analysis demonstrated lower levels of TGFbeta1 in BL6T lung metastases compared with BL6 lung metastases. On the other hand, higher levels of this cytokine, in particular in its active form, occur in the plasma of BL6T metastasized animals, suggesting a nPKCdelta-dependent TGFbeta1 release. Therefore, nPKCdelta-dependent TGFbeta1 release and activation may be involved in the greater angiogenic and metastatic capacity of murine melanoma BL6T cells. PMID- 11198474 TI - Lack of vasopressin expression in malignant melanomas. PMID- 11198475 TI - Comparative study of the expression of DNA mismatch repair genes, the adenomatous polyposis coli gene and growth arrest DNA damage genes in melanoma recurrences and metastases. AB - The main goal of this study was to examine the expression of DNA mismatch repair genes (MLH1, MSH2, PMS1 and PMS2), the adenomatous polyposis coli (APC) gene and growth arrest DNA damage inducible (GADD) genes (GADD34, GADD45 and GADD153) in the different stages of melanoma recurrences and metastases, and to identify any mutual consistencies in their expression pattern. All the cases of primary melanoma examined showed a reduced expression of DNA repair genes. These results demonstrate that disturbances of DNA repair begin in the early stages of melanoma. No significant differences were found in the expression of these markers between cutaneous melanomas and their recurrences and metastases (P> 0.05). Eighteen significant correlations between markers were found in the primary melanomas, and 10 significant correlations were observed in the first recurrences of melanoma. In contrast, 27 statistically significant relationships were demonstrated in metastatic lymph nodes. The different correlations found in primary and metastatic tumours confirmed the hypothetical difference in marker interaction in the diagnostic groups investigated. Our results suggest that DNA repair genes may play an important role in the recurrence and metastasis of melanomas. PMID- 11198476 TI - Role of RT-PCR tyrosinase detection in the monitoring of patients with advanced metastatic melanoma. AB - In recent studies a new method has been proposed to detect circulating melanoma cells in the peripheral blood of patients, based on the amplification of the mRNA for tyrosinase, an enzyme involved in melanin biosynthesis that is expressed only by melanocytic cells. The sensitivity and clinical relevance of this method are still controversial. In the present study, 596 blood samples from 186 melanoma patients at various clinical tumour stages, together with samples from 25 healthy volunteers, were analysed with the aim of investigating the value of tyrosinase detection in predicting melanoma recurrence. We suggest a possible role for this marker in the monitoring of melanoma patients after the excision of regional lymph node metastases, and provide evidence that tyrosinase is related to the status of disease in advanced metastatic patients. Moreover, chemotherapy administration appeared to influence tyrosinase determination and may explain the discrepancies in the reported percentages of positive samples. PMID- 11198477 TI - Computer-aided epiluminescence microscopy of pigmented skin lesions: the value of clinical data for the classification process. AB - Early melanoma is often difficult to differentiate from benign pigmented skin lesions (PSLs). Digital epiluminescence microscopy (DELM) and automated image analysis could represent possible aids for inexperienced clinicians. We designed an automated computerized image analysis system that has the potential for use as an additional tool for the differentiation of melanoma from dysplastic naevi and common naevi. The PC-based pilot system was attached to a common DELM system as the image source. Digital images of PSLs were automatically segmented and a panel of 107 morphological parameters were measured. Additionally, seven clinical parameters were evaluated and used as an additional source of information. Neural networks were then trained to distinguish melanoma from benign PSLs. One class of networks was trained solely based on the morphometric features, whereas the second class of networks was trained on the combination of morphometric and clinical features. The automatic segmentation algorithm was correct in 96% of cases. Using three-way receiver operating characteristic (ROC) analysis, for networks trained solely on morphometric features the volume under surface (VUS) was 0.617 (SD 0.036). The performance was significantly better for networks trained on the combination of both morphometric and clinical features (VUS = 0.682, SD 0.035). In a dichotomous model, distinguishing benign lesion (common naevi + dysplastic naevi) from melanoma, the area under the curve (AUC) from two way ROC analysis was 0.942 (SD 0.018) for networks trained solely on morphometric features and 0.968 (SD 0.012) for those trained on the combination of clinical and morphometric data (P= NS). Automated feature extraction from PSLs and the training of neural networks as classifiers has thus shown satisfactory performance in a large scale experiment. The addition of clinical data significantly increases the diagnostic performance for distinguishing three classes of lesions (i.e. common naevi, dysplastic naevi and melanoma). Such integrated systems hold promise as a decision aid for the diagnosis of PSLs. PMID- 11198478 TI - Precision of automatic measurements of pigmented skin lesion parameters with a MelaFind(TM) multispectral digital dermoscope. AB - The purpose of this study was to assess the precision of automatic computerized measurement of parameters that may be useful in the differentiation of malignant melanoma from benign pigmented skin lesions, and also to determine the feasibility of quantitative monitoring of skin lesions over time. Ten independent sequences of images were acquired with a MelaFind multispectral digital dermoscope for each of 12 benign or malignant pigmented skin lesions. The sequences of images were processed automatically to provide 10 independent measurements of the various parameters for each lesion. Parameters included lesion area, greatest 'diameter', perimeter, reflectance and asymmetry. The precision of each parameter determination was computed from the mean and standard deviation of the 10 measurements of that parameter. The relative errors in determining the lesion area, 'diameter' and perimeter were found to be 6%, 3% and 4%, respectively. Other lesion parameters that are used in differentiating melanomas from benign skin lesions were also analysed as a function of wavelength. In the blue band (about 430 nm) the relative error was about 7% for the mean lesion reflectance and about 7% for the asymmetry parameter. These results demonstrate the feasibility of using MelaFind for objective quantitative monitoring of changes in pigmented skin lesions over time. As suggested by some studies, such information is useful in the early detection of malignant melanoma. The results show that parameters obtained automatically from MelaFind images are sufficiently precise to allow pertinent parameters to be used to classify pigmented skin lesions. PMID- 11198479 TI - Plantar malignant melanoma -- a challenge for early recognition. AB - The incidence of malignant melanoma has been continuously increasing over the last few decades. Non-plantar melanomas are nowadays usually diagnosed and treated surgically at an early stage. In contrast, melanoma in a plantar location is usually diagnosed at an advanced tumour stage, conferring a poor prognosis. To discover the reasons for this remarkable difference in recognition and prognosis, we analysed our cases of plantar malignant melanoma in a retrospective study. From 1990 to 1997, we treated 925 melanoma patients. Of these, 68 cases (7%) were classified as plantar melanoma. For non-plantar melanoma patients the mean age was 52.6 years, the mean Clark level was 2.8 and the mean tumour depth was 1.22 mm. In contrast, the mean age of patients with plantar melanoma was 63.3 years, the mean Clark level was 3.61 and the mean tumour depth was 2.55 mm. The mean time between the first observation of the plantar skin lesion and the first consultation with a physician (patients' delay) was 4.8 years and, on average, it took an additional 7 months before adequate surgical treatment was performed (physicians' delay). The prognosis of our patients was poor. In 98.5% (n = 67) further metastases were observed on follow-up. Since there is still no cure for advanced plantar malignant melanoma, the early detection and subsequent surgical treatment of plantar melanoma is decisive for the prognosis. Based on our results, the poor survival can be improved by a significant reduction in the time period between the first observation of a plantar skin lesion and surgical treatment. Therefore there is an urgent need for special preventive health care campaigns to reduce significantly both the patients' and the physicians' delay. PMID- 11198480 TI - In vivo electroporation of plasmids encoding GM-CSF or interleukin-2 into existing B16 melanomas combined with electrochemotherapy induces long-term antitumour immunity. AB - When cancer cells, including melanoma cells, are genetically altered to secrete cytokines, irradiated and injected into subjects, long-term antitumour immunity is induced. Optimally, existing melanomas induced to produce cytokines in vivo could stimulate this same immune response. Although in vivo electroporation enhances plasmid expression, electroporation of plasmids encoding granulocyte monocyte colony stimulating factor (GM-CSF) and interleukin-2 (IL2) into B16 mouse melanomas did not significantly alter tumour growth at the concentration tested. Electrochemotherapy, which causes short-term, complete regressions of treated tumour but no resistance to challenge, was combined with plasmid delivery. The combination treatment resulted in the induction of long-term immunity to recurrence and resistance to challenge in up to 25% of mice. PMID- 11198481 TI - Efficient palliation of haemorrhaging malignant melanoma skin metastases by electrochemotherapy. AB - Electric pulses can cause transient permeabilization of cell membranes (electroporation) and this can be utilized to increase the uptake of chemotherapy (electrochemotherapy). Preclinical studies have shown that in vivo electroporation causes transient shut down of blood flow both in normal and, in particular, malignant tissues. We report the successful palliation of a malignant melanoma patient with bleeding skin metastases using electrochemotherapy. In an on-going study of combined electrochemotherapy and low dose interleukin-2, one patient with bleeding skin metastases was included. Nine skin metastases, of which seven were ulcerated, were treated. After intratumoral bleomycin injection, needle electrodes with two arrays 4 mm apart were inserted into the tumours. Eight square wave electric pulses each 99 micros in duration and with an applied voltage to electrode distance ratio of 1.2 kV/cm were administered. In all the treated lesions, bleeding immediately stopped on administration of the electric pulses and did not recur. The treated metastases developed crusts and the lesions healed in a matter of weeks. Treatments were given under local anaesthesia, lasted a few minutes, and patient discomfort was brief and modest. In conclusion, we propose that electrochemotherapy should be considered for the palliation of haemorrhaging metastases as it is an efficient, tolerable, brief, outpatient, once-only treatment. PMID- 11198482 TI - Baroreflex dysfunction induced by microgravity: potential relevance to postflight orthostatic intolerance. AB - Microgravity imposes adaptive changes in the human body. This review focuses on the changes in baroreflex function produced by actual spaceflight, or by experimental models that simulate microgravity, e.g., bed rest. We will analyze separately studies involving baroreflexes arising from carotid sinus and aortic arch afferents ("high-pressure baroreceptors"), and cardiopulmonary afferents ("low-pressure receptors"). Studies from unrelated laboratories using different techniques have concluded that actual or simulated exposure to microgravity reduces baroreflex function arising from carotid sinus afferents ("carotic cardiac baroreflex"). The techniques used to study the carotid-cardiac baroreflex, using neck suction and compression to simulate changes in blood pressure, have been extensively validated. In contrast, it is more difficult to selectively study aortic arch or cardiopulmonary baroreceptors. Nonetheless, studies that have examined these baroreceptors suggest that microgravity produces the opposite effect, ie, an increase in the gain of aortic arch and cardiopulmonary baroreflexes. Furthermore, most studies have focus on instantaneous changes in heart rate, which almost exclusively examines the vagal limb of the baroreflex. In comparison, there is limited information about the effect of microgravity on sympathetic function. A substantial proportion of subjects exposed to microgravity develop transient orthostatic intolerance. It has been proposed that alterations in baroreflex function play a role in the orthostatic intolerance induced by microgravity. The evidence in favor and against this hypothesis is reviewed. PMID- 11198483 TI - Vascular responses to orthostatic stress in patients with postural tachycardia syndrome (POTS), in patients with low orthostatic tolerance, and in asymptomatic controls. AB - Patients with postural tachycardia syndrome (POTS) are characterized by development of symptoms of orthostatic intolerance during standing that are not because of hypotension but are associated with tachycardia. The goal of this study was to compare the cardiac and vascular responses to orthostatic stress for patients with POTS (n = 8) with those for patients with low orthostatic tolerance (n = 29) and for healthy control subjects (n = 12). Responses of heart rate (ECG), arterial blood pressure, and brachial artery blood velocity (Doppler) were determined during a progressive orthostatic stress test of head-up tilt and lower body suction. Changes in forearm vascular resistance (mean arterial pressure/brachial velocity) were less for patients with POTS than for healthy persons, and also less than for most of the patients with low orthostatic tolerance. However, patients with POTS did not have a low tolerance to orthostatic stress (measured as time to discontinuation of the test). For the patients with POTS, the test was discontinued often because of symptoms associated with tachycardia but not hypotension, whereas for the other two groups, the test was discontinued because of hypotension. This study shows that for patients with POTS, abnormal sympathetic responses exist, with an increased sympathetic drive to the heart but deficient peripheral vascular responses, as measured in the forearm. This supports the hypothesis that patients with POTS may have a selective peripheral neuropathy, with small responses in some regions being compensated by overactivity in other regions. PMID- 11198484 TI - Noninvasive detection of sympathetic neurocirculatory failure. AB - In sympathetic neurocirculatory failure (SNF), reflexive sympathetically mediated cardiovascular stimulation does not compensate for decreased cardiac filling. This explains orthostatic hypotension in chronic primary autonomic failure (CPAF). During phase 2 of the Valsalva maneuver (phase 2_L), blood pressure increases from its peak. During phase 4, blood pressure normally "overshoots" the baseline. Because these changes depend on sympathetically mediated cardiovascular stimulation, a progressive decrease in pressure during phase 2 and absence of the overshoot in phase 4 may indicate SNF. Moreover, because beat-to-beat blood pressure can be measured noninvasively using a photoplethysmographic or tonometric device, evaluating reflexive pressure responses might enable noninvasive diagnosis of SNF. This study assessed the relative frequencies of abnormal phase 2_L and phase 4 blood pressure in patients with CPAF and orthostatic hypotension and whether noninvasive measurement of beat-to-beat blood pressure can be used to diagnose SNF in patients. Twenty patients with chronic primary autonomic failure and orthostatic hypotension and 50 comparison patients, including several with CPAF but lacking orthostatic hypotension, underwent arterial pressure monitoring during performance of the Valsalva maneuver. Of the 20 patients with CPAF and orthostatic hypotension, all had an abnormal phase 2_L or phase 4 pressure response (sensitivity 100%), whereas only 3 of the 50 comparison patients had an abnormal response in either phase (specificity 94%). Seventeen patients with CPAF and orthostatic hypotension had abnormal responses in both phases (sensitivity 85%), but none of the comparison patients had such findings in both phases (specificity 100%). Of 13 patients in whom beat-to-beat blood pressure was recorded simultaneously invasively and noninvasively, all had abnormal blood pressure responses during phase 2_L and phase 4, whereas none of 29 comparison patients had such symptoms. Detection of abnormal blood pressure responses during phase 2_L or phase 4 of the Valsalva maneuver is a highly sensitive test for SNF. Abnormal pressure during these phases appears to identify SNF specifically. Noninvasive measurements can detect both of these abnormalities. PMID- 11198485 TI - Clinical improvement in patients with orthostatic intolerance after treatment with bisoprolol and fludrocortisone. AB - Orthostatic intolerance is the development of disabling symptoms upon assuming an upright posture that are relieved partially by resuming the supine position. Postural tachycardia syndrome (POTS) is an orthostatic intolerance syndrome characterized by palpitations because of excessive orthostatic sinus tachycardia, lightheadedness, tremor, and near-syncope. Patients usually undergo extensive medical, cardiac, endocrine, neurologic, and psychiatric evaluation, which usually fails to identify a specific abnormality. The authors investigated the autonomic and hemodynamic profile of patients with POTS and the effectiveness of bisoprolol and fludrocortisone. The authors evaluated 11 female patients with POTS before and after medical treatment with a cardioselective bisoprolol beta blocker or fludrocortisone, or both, and 11 age-matched control patients. Variability of heart rate and systolic blood pressure was assessed by fast Fourier transform, and spontaneous baroreceptor gain was assessed by use of the temporal sequences slope and alpha index. Modelflow was used to quantify hemodynamics. Symptoms in all patients improved greatly after medication. The autonomic and hemodynamic impairment observed in patients with POTS, particularly after orthostatic stress, is treated effectively with bisoprolol or fludrocortisone or both. These results need further confirmation in a controlled double-blind study. Proper medical treatment improves dramatically the clinical and autonomic-hemodynamic disturbances observed in patients with POTS. The data support the hypothesis that POTS is the result of a hyperadrenergic activation or hypovolemia during orthostasis. PMID- 11198487 TI - Lack of autonomic nervous dysfunction in progressive supranuclear palsy, a study of blood pressure variability. AB - Blood pressure and heart rate variability were analyzed in eight patients with progressive supranuclear palsy in comparison with two control groups (10 healthy patients and 10 patients with multiple system atrophy). Blood pressure and heart rate were recorded using digital photoplethysmography with the patient in supine position and during a head-up-tilt test (70 degrees for 10 minutes). Spectral analysis was performed using fast Fourier transformation for 512 consecutive systolic blood pressure and heart rate values. The head-up-tilt test induced a significant increase in systolic blood pressure in patients with progressive supranuclear palsy and in healthy patients and a significant systolic blood pressure decrease in patients with multiple system atrophy. During the head-up tilt test, low-frequency energy of systolic blood pressure (70-130 mHz) that reflected baroreflex-dependent sympathetic tone also increased in patients with progressive supranuclear palsy and in healthy patients. By contrast, in patients with multiple system atrophy, the low-frequency energy of systolic blood pressure decreased significantly. The changes observed in the low-frequency band and the high-frequency band of heart rate (reflecting parasympathetic drive to the heart) were not different among the three groups. These data show the lack of impairment in autonomic nervous system activity in patients with progressive supranuclear palsy. PMID- 11198486 TI - Sympathoadrenal activation and the dumping syndrome after gastric surgery. AB - Dumping symptoms suggest concomitant sympathoadrenal activation. To evaluate the relation between dumping symptoms and postprandial plasma catecholamine changes, standardized dumping-provocation tests with use of oral glucose were performed for 16 gastric surgery patients with dumping, for 14 gastric surgery patients without dumping, and for 14 healthy control patients. Early dumping symptoms were present for all patients with dumping, and late symptoms developed in three patients with dumping after glucose ingestion. Patients without dumping and healthy control patients had slight complaints or no complaints. Systolic and diastolic blood pressure remained unaffected for the three groups. Positive breath-hydrogen tests, heart rate increments, and reactive plasma glucose decrements were present for patients with dumping and for patients without dumping, but not for control patients. Plasma noradrenaline and adrenaline increased for patients with dumping and for patients without dumping, but not for control patients. The noradrenaline increment was higher for patients with dumping (98%) than for patients without dumping (78%; p <0.05). The noradrenaline increment was related to the dumping score and to the heart rate increment for the first hour after glucose ingestion, whereas the adrenaline increment was related to the plasma glucose decrement for the third hour. Therefore, dumping symptoms clearly are accompanied by postprandial sympathoadrenal activation, but sympathoadrenal activation cannot account completely for development of dumping symptoms. PMID- 11198488 TI - Autonomic studies in hypertensive patient with unusual sexual dysfunction: response to reserpine. AB - The authors examined a 48-year-old man with a history of hypertension (6 years) and a history of erection and ejaculation during cold exposure and confrontation with fear (20 years). Exposing the foot to cold water induced ejaculation in 10 seconds. A variety of antihypertensive medications resulted in control of hypertension, without improvement in ejaculatory dysfunction. Similarly, prazosin controlled the blood pressure, but not the episodes of ejaculation. Treatment with reserpine resulted in gradual reduction in blood pressure and an improvement in ejaculatory dysfunction. PMID- 11198489 TI - Oral mucosal blood flow following dry ice stimulation in humans. AB - The aim of the current pilot study was to establish a procedure that would allow the investigation of microcirculatory changes in the oral cavity. The authors studied the effects of painful stimulation using dry ice (CO2). To investigate potential regional differences in the change of blood flow, recordings were made for the tongue and at the mucosa of the hard palate, lip, and oral vestibule. The authors investigated 26 patients divided into groups of younger subjects (10 men, 3 women; age range 21-31 y) and older patients (2 men, 11 women; age range 54-74 y). Mucosal blood flow (mBF) was obtained at the hard palate, at the tip of the tongue, on the midline of the oral vestibule, and at the lip. Measurements were made during rest and for 2 minutes after application of dry ice for a 10-second duration, using a pencil-shaped apparatus. Blood pressure, heart rate, cutaneous blood flow, transcutaneous partial pressure of carbon dioxiode (PCO2) and partial pressure of oxygen (PO2) were recorded. Mucosal blood flow increased at all sites in response to application of dry ice (p <0.001), with peak flow at 0.5 minute to 1.5 minutes after onset of stimulation. During the 1.5 minutes to 2 minutes, blood flow decreased at all measurement sites with a tendency to return to baseline. Heart rate, blood pressure, pCO2, PO2, and cutaneous blood flow did not show significant changes. Overall, responses in older patients showed more variance when compared with younger patients. Stimulation by dry ice appears to be an effective, noninvasive, and tolerable means to investigate mucosal blood flow at different mucosal sites. Preliminary data indicate different levels of responsiveness to painful cold stimulation at different sites on the oral and perioral mucosa; particularly, mucosal blood flow response at the tongue was least pronounced. Therefore, assessment of stimulated mucosal blood flow appears to be a promising tool to investigate the pathophysiology of a number of neurologic symptoms, eg, the burning mouth syndrome. PMID- 11198490 TI - Outcome measures in pediatric neurology: why do we need them? AB - Outcome measures should include the patient's values and preferences (from the patient's perspective) in addition to performance ratings and physiologic states. Outcome measures can assess relationships between services and interventions and their end results, can clarify which therapies are worth providing and which therapies need more evidence about their effectiveness, and can measure the burdens of different disorders and interventions. Researchers recently have shown the feasibility of creating and using outcome measures for children with neurodevelopmental disorders. Clinicians may wish to familiarize themselves with the concepts of outcome measures and health-related quality of life in order to understand the rationale, utility, properties, and various types of outcome measures in order to select the most appropriate instruments that will best serve their patient populations. Ongoing research efforts are currently using such measures in children with central nervous system tumors, with neural tube defects, and of extremely low birthweight; in childhood and adolescent epilepsy; and in adolescents with headaches. PMID- 11198491 TI - Six-year follow-up of children with intrauterine growth retardation: long-term, prospective study. AB - This prospective study was designed to characterize the neurodevelopmental and cognitive difficulties specific to children with intrauterine growth retardation and to detect early clinical predictors of these difficulties. Eighty-one children with intrauterine growth retardation were monitored up to 6 to 7 years of age using biometric parameters, perinatal risk questionnaires, and detailed neurodevelopmental and cognitive assessments. Forty-one children served as age matched, appropriate for gestational age controls. A significant difference in growth parameters (P < .001), neurodevelopmental score (P < .05), and IQ (P < .05) was found between the children with intrauterine growth retardation and controls. A specific profile of difficulties in coordination, lateralization, spatial and graphomotor skills, and abundance of associated movements is typical of the children with intrauterine growth retardation and hints at possible later learning disabilities. The clinical parameters best predicting neurodevelopmental outcome were the neonatal risk score (P < .05) and the weight and height at 6 years of age (P < .05). The children with intrauterine growth retardation with neonatal complications had lower neurodevelopmental scores than the controls but no difference in IQ. Intrauterine growth retardation children diagnosed prenatally had the same neurodevelopmental and IQ scores as those diagnosed at birth, probably due to the careful perinatal and obstetric care provided. Children with intrauterine growth retardation demonstrate a specific profile of neurodevelopmental disabilities at preschool age. Early diagnosis and intervention could probably reduce these difficulties to a minimum. PMID- 11198492 TI - The ketogenic diet: seizure control correlates better with serum beta hydroxybutyrate than with urine ketones. AB - The objective of this study was to determine the relationship between beta hydroxybutyrate levels and seizure control in children on the ketogenic diet. Seventy-four children on the ketogenic diet presenting for routine follow-up visits had blood levels of beta-hydroxybutyrate correlated with their seizure control. Forty-two children admitted for initiation of the ketogenic diet had urine ketones measured by dipstick and correlated with simultaneous blood levels of beta-hydroxybutyrate. Blood beta-hydroxybutyrate levels statistically correlated with seizure control (P = .003). Children with blood beta hydroxybutyrate levels greater than 4 mmol/L were significantly more likely to have a decrease in seizure frequency than those with levels less than 4 mmol/L. Urine ketones of 4+ (160 mmol/L) were found on dipstick when blood beta hydroxybutyrate levels exceeded 2 mmol/L. Seizure control correlates with blood beta-hydroxybutyrate levels and is more likely when blood beta-hydroxybutyrate levels are greater than 4 mmo/L. The traditional measurement of urine ketones by dipsticks in children on the ketogenic diet provides a less than optimal assessment of the degree of blood ketosis. Three to four plus (80-160 mmol/L) urine ketones are necessary, but not necessarily sufficient, to achieve optimal seizure control in children on the ketogenic diet. At present, however, urine ketones are the only readily available inexpensive approach to ketone assessment. PMID- 11198493 TI - Persistent preceding focal neurologic deficits in children with chronic Epstein Barr virus encephalitis. AB - Epstein-Barr virus encephalitis is a self-limiting disease with few sequelae. Persistence of neurologic deficits prior to and after the acute illness has yet to be described in children. We describe five children with persistent cognitive and focal neurologic deficits due to chronic Epstein-Barr virus encephalitis with various T2-weighted magnetic resonance imaging abnormalities. Clinical features were a 9-year-old boy with aphasia and apraxia, an 11-year-old girl with impulsivity and inappropriate behavior, a 17-year-old boy with deterioration of cognitive skills and judgment, a 5-year-old boy with complex-partial seizures, and a 6-year-old girl with obsessive-compulsive behavior. All patients had elevated serum Epstein-Barr virus titers for acute infection, with cerebrospinal fluid polymerase chain reaction positive for Epstein-Barr virus in four patients. Three children were treated with methylprednisolone with minimal improvement without changes on magnetic resonance imaging. Epstein-Barr virus encephalitis can present with chronic and insidious neurologic symptoms and should be considered in the differential diagnosis of children with acute or chronic neurologic illness of unknown etiology. PMID- 11198494 TI - Insulin-like growth factor-I in cerebrospinal fluid and serum in Rett syndrome. AB - Rett syndrome is a neurodevelopmental disease characterized by failure of somatic and brain growth. The insulin-like growth factor system mediates most actions of growth hormone. Evidence that it plays an important role in early development of the brain is increasing. The aim of the study reported was to assess the role of the insulin-like growth factor system in the pathogenesis of Rett syndrome. We measured insulin-like growth factor-I levels in serum (8 patients, mean age 9.1 years) and cerebrospinal fluid (13 patients, mean age 7 years) using a sensitive radioimmunoassay method and compared them with those in age-matched controls (13 and 26 patients, respectively). Neither serum nor cerebrospinal fluid insulin like growth factor-I levels differed from those in controls. We also measured insulin-like growth factor binding protein-3 levels in serum (in 9 patients and 8 controls) and in cerebrospinal fluid (in 12 patients and 11 controls) and serum growth hormone levels (in 8 patients and 11 controls); the levels in patients did not differ from those in controls. We found no significant correlation between serum and cerebrospinal fluid insulin-like growth factor-I in Rett syndrome. This may indicate an independent role of insulin-like growth factor system in the central nervous system, making serum insulin-like growth factor-I measurement unreliable as an indicator of disturbed function in the central nervous system. Our results did not support the notion that a defective insulin-like growth factor-I system explains the lack of somatic and brain growth in Rett syndrome. PMID- 11198495 TI - Neurologic symptoms in children with systemic lupus erythematosus. AB - Neurologic complications of systemic lupus cerebritis are not as well known in children as in adults. Twenty-five children with neurologic complications were identified after reviewing the hospital medical records of 86 children with systemic lupus erythematosus. Seven children (28%) had neurologic symptoms at the time of initial diagnosis of systemic lupus erythematosus; median time between diagnosis of systemic lupus erythematosus and onset of neurologic complications was 1 month (range 0-5 years). Seizures were the most common neurologic symptoms overall, but headaches were the most frequent neurologic manifestation in children without a previous diagnosis of systemic lupus erythematosus. Sixteen children had seizures, and 12 children had seizures as the initial central nervous system involvement. Almost all children who developed seizures had an established diagnosis of systemic lupus erythematosus; only one child had seizures that led to the diagnosis of systemic lupus erythematosus. No patient had status epilepticus, and, in general, seizures were not difficult to control. In six children, headache was the initial symptom of central nervous system involvement. Five children had lupus cerebritis, three children had stroke, and two had isolated cranial neuropathies. Chorea was seen in only two cases, and three children had pseudotumor cerebri. Treatment with high-dose intravenous methylprednisolone led to a good response in 18 children; cyclophosphamide was required in 6 patients and plasmapheresis in 1 child. Outcome was generally good, although one child developed fulminant cerebritis with intracranial hypertension and died. PMID- 11198496 TI - Asymmetric crying facies and associated congenital anomalies: prospective study and review of the literature. AB - Congenital asymmetric crying facies, a minor congenital anomaly due to absence or hypoplasia of the depressor anguli oris muscle on one side of the mouth, is associated at times with major congenital anomalies, most commonly in the cardiovascular system. In a prospective study of 5532 infants born at the Assaf Harofeh Medical Center, Israel, during 12 months (January to December 1998), 17 infants (an incidence of 0.31%) had asymmetric crying facies. One of the affected infants had ventricular septal defect and another infant had VATER (vertebral defects, imperforate anus, tracheoesophageal fistula, and radial and renal dysplasia) syndrome. No noxious obstetric perinatal factors could be identified. Family history was unremarkable in all cases. Diagnostic work-up performed in all of the affected infants failed to reveal an additional congenital malformation. Asymmetric crying facies is a minor isolated finding in most of the cases; however, a thorough search for other congenital malformations, especially of the cardiovascular system, should be performed. PMID- 11198497 TI - Febrile convulsions after 5 years of age: long-term follow-up. AB - In order to examine the natural history of febrile convulsions occurring after 5 years of age, we studied 44 children in whom febrile convulsions persisted after 5 years of age (group 1) and compared their development of unprovoked seizures with a group of 195 children in whom febrile convulsions occurred before 5 years of age (group 2). All subjects of group 1 were re-evaluated at the mean age of 13.4+/-1.7 years. The children in group 2 were followed up until they reached the same mean age as children in group 1 (13.1+/-2.3 years). In group 1, we found a higher percentage of unprovoked seizures than in children with febrile convulsions with onset before 5 years of age (18.1% vs 7.4%, P < .05). Our data suggest that children with febrile convulsions after 5 years of age probably must be considered as a group of patients at risk of developing unprovoked seizures. PMID- 11198498 TI - Reflections. PMID- 11198499 TI - Hypotension following the initiation of tizanidine in a patient treated with an angiotensin converting enzyme inhibitor for chronic hypertension. AB - Centrally acting alpha-2 adrenergic agonists are one of several pharmacologic agents used in the treatment of spasticity related to disorders of the central nervous system. In addition to their effects on spasticity, certain adverse cardiorespiratory effects have been reported. Adults chronically treated with angiotensin converting enzyme inhibitors may have a limited ability to respond to hypotension when the sympathetic response is simultaneously blocked. The authors present a 10-year-old boy chronically treated with lisinopril, an angiotensin converting enzyme inhibitor, to control hypertension who developed hypotension following the addition of tizanidine, an alpha-2 agonist, for the treatment of spasticity. The possible interaction of tizanidine and other antihypertensive agents should be kept in mind when prescribing therapy to treat either hypertension or spasticity in such patients. PMID- 11198500 TI - Evidence for altered basal ganglia and cortical functions in transient idiopathic dystonia. AB - Idiopathic dystonia with onset in the first year of life has been described as a transient movement disorder, in contrast to other forms of idiopathic dystonia We report on a girl who showed, from her 5th month, episodes of dystonic postures of her neck and arm, which lasted for seconds and occurred several times a day. Neurologic findings and the psychomotor development were and remained normal. Neurometabolic screening tests and cerebral magnetic resonance imaging showed normal results. Functional cerebral imaging showed decreased perfusion of the basal ganglia and the left temperomesial cortex using single photon emission computed tomography (SPECT with technetium 99m hexamethylpropyleneamine oxime [99mTc-HMPAO]) and decreased glucose metabolism in the basal ganglia and the cerebellum using positron emission tomography (PET with [18F]fluorodeoxyglucose [18FDG]). Follow-up revealed that the episodes disappeared at the age of 16 months. The findings of PET and SPECT give evidence of an alteration in basal ganglia function but also in functions of other central nervous system regions, which may, however, be temporary. PMID- 11198501 TI - Mitochondrial DNA depletion in children. AB - The first girl of an unrelated couple was noted to have failure to thrive since age 3 months, generalized hypotonia and weakness, hepatomegaly, hypoglycemia, and lactic acidosis at 4 months. She was found to have severe mitochondrial DNA (mtDNA) depletion and respiratory chain complex IV deficiency in both skeletal muscle and liver but without other common mtDNA mutations. Her younger brother developed vomiting at age 3 weeks and was diagnosed as having pyloric stenosis. His skeletal muscle and liver also showed severe mtDNA depletion. He developed generalized weakness and hypotonia, hepatomegaly, and lactic acidosis at age 3 months. Both siblings died of hepatic failure and hemorrhagic complication before 6 months of age. The brother also had chemical pancreatitis, which had not been reported before in mtDNA depletion in children. Severe mtDNA depletion may present with nonspecific symptoms such as vomiting, failure to thrive, and developmental delay; multiorgan involvement such as hepatomegaly, pancreatitis, and myopathy occurs later. Mitochondrial DNA depletion should be considered in the differential diagnosis in children with developmental delay or failure to thrive of unknown etiology. PMID- 11198502 TI - Cerebellar involvement in Langerhans' cell histiocytosis: a progressive neuropsychiatric disease. AB - We describe a 21-year-old patient who was being followed since the age of 3(1/2) years for Langerhans' cell histiocytosis. Although previously a bright and gifted student, the patient presented at age 16(1/2) with new-onset cerebellar neurologic signs, obsessive-compulsive disorder, and dementia. Findings on magnetic resonance imaging study of the brain were normal, but brain single photon emission computed tomography with technetium 99m ethylene cysteinate dimer showed markedly decreased cerebellar perfusion. This case is unique for the wide extent of the central nervous system involvement in Langerhans' cell histiocytosis, which has not been reported previously. Although obsessive compulsive disorder has also been associated with several other cerebellar disorders, it is still unknown whether the cerebellum plays a role in its development. We suggest that in some cases, brain single photon emission computed tomography may be superior to magnetic resonance imaging for demonstrating cerebellar disorder in Langerhans' cell histiocytosis. PMID- 11198503 TI - Severe migraine associated with coarctation of aorta: complete recovery following balloon dilation. AB - We report on a rare association of severe migraine headaches associated with coarctation of aorta that completely resolved following dilation of the constricted aorta. A 6-year-old girl presented with severe pounding headaches accompanied with recurrent vomiting, associated with photophobia and phonophobia. She experienced frequent awakenings with severe headaches and vomiting. The described excruciating, prolonged, and practically persistent headaches were not relieved by analgesics and ergotamines. Neurologic assessment and brain computed tomography were both normal. A systolic murmur at the third right intercostal space prompted a cardiac echocardiogram, which demonstrated coarctation of the ascending aorta beyond the orifice of the left common carotid artery. Catheterization revealed a systolic gradient of 54 mm Hg, and the constricted lumen of the aorta was then dilated by a balloon. The excruciating vascular headaches and associated symptoms had abated instantaneously following this procedure. To the best of our knowledge, this is the first report associating severe migraine headaches in a child with coarctation of the aorta. Given complete recovery following balloon dilation of the aorta, cardiac echocardiogram should be added to the diagnostic battery of children with severe unresponsive migraine. PMID- 11198504 TI - Intravenous valproate dosing in neonates. AB - The loading dosage of intravenous valproate required to achieve a desired serum concentration in neonates is not known. Two neonates with seizures received loading doses of intravenous valproate over 30 minutes. Serum valproate concentrations were measured 45 minutes and 3 hours after initiation of the infusion. Both neonates had received phenobarbital and phenytoin before the loading infusions. In the first patient, a loading dose of intravenous valproate of 10 mg/kg increased the 45-minute postinfusion serum valproate concentration to 41 microg/mL with a 3-hour postinfusion serum valproate concentration of 33 microg/mL. In the second patient, a loading dose of 25 mg/kg increased the 45 minute postinfusion serum valproic acid concentration to 100 microg/mL with a 3 hour postinfusion serum valproic acid concentration of 78 microg/mL. We found that each 1 mg/kg of intravenous valproate increased the 45-minute and 3-hour postinfusion serum valproic acid concentrations by approximately 4 microg/mL and 3 microg/mL, respectively. We suggest that these figures be used to calculate the desirable loading dose of intravenous valproate in neonates until larger studies are conducted. The volume of distribution and the serum clearance of valproate were approximately 0.245 L/kg and 25 mL/h/kg, respectively. PMID- 11198505 TI - Fatal infantile X-linked neuropathy. AB - We report a pedigree with severe X-linked neuropathy that occurs in male infants and results in death, typically by 2 years of age. The proband of our report was weak with preserved mentation. He underwent extensive evaluation, which revealed abnormal nerve conduction studies, neurogenic changes on muscle biopsy, a decreased number of large myelinated fibers and rare onion bulb formations on nerve biopsy, negative gene testing for spinal muscular atrophy, CMT1a, and CMTX1 and a normal brain magnetic resonance image. The proband's mother, an obligate carrier, had normal nerve conduction studies. Male infants with a spinal muscular atrophy phenotype but normal genetic studies should be evaluated for this fatal X linked neuropathy. PMID- 11198506 TI - Mitochondrial DNA point mutation T9176C in Leigh syndrome. AB - Leigh syndrome is a progressive neurodegenerative disease frequently associated with mitochondrial abnormalities. The mitochondrial DNA T9176C mutation in the adenosine triphosphatase 6 gene has recently been described as a cause of Leigh syndrome. Leukocyte DNA from 59 children with Leigh syndrome was screened for the T9176C mutation by conventional polymerase chain reaction methods. Two unrelated patients were found to be homoplasmic for this mutation in blood. Both patients had similar clinical and biochemical features. They had first presented acutely at 3 and 5 years, respectively, with ataxia and slurred speech. Magnetic resonance imaging changes were consistent with Leigh syndrome, and the cerebrospinal fluid lactate was elevated. They have both had relatively stable disease since the time of diagnosis. The mother of one of the children had presented at age 29 years with sudden onset of ataxia, headache, and blurred vision. She was heteroplasmic for the T9176C mutation. The T1976C is an important cause of Leigh syndrome especially in the subgroup of patients with more stable disease and normal respiratory chain enzyme analysis. PMID- 11198507 TI - Nasal midazolam effects on childhood acute seizures. AB - Sixteen children, aged from 2 months to 14 years, with a diagnosis of acute seizures and seen at Dr. Sami Ulus Child Health and Disease Center, were included in this study. Midazolam (5 mg/mL) 0.2 mg/kg was administered intranasally in 30 seconds by an injector. The heart rate, respiratory rate, blood pressure, and oxygen saturation were recorded at 0, 5, and 10 minutes after administration. The seizures of three (18.7%) patients terminated within 1 minute, of seven (43.7%) patients in 1 to 2 minutes, and of three (18.7%) patients in 2 to 5 minutes. However, three (18.7%) patients did not respond to treatment. As a result, it was concluded that intranasal midazolam administration is easy and effective. The half-life of midazolam is shorter than diazepam, and midazolam has fewer complications when compared with diazepam. It is easier to use in nasal drop and spray forms. PMID- 11198508 TI - Gelastic seizures of neocortical origin confirmed by resective surgery. AB - Ictal laughter is a relatively unusual phenomenon that appears to arise from within hypothalamic hamartomas. Gelastic seizures of neocortical origin are rare and when reported typically originate from temporofrontal regions in proximity to the hypothalamus, raising the possibility of a subtle lesion in the hypothalamus. A girl with gelastic seizures originating in a dysembryoblastic neuroepithelial tumor at the cranial vertex had resolution of her seizures following surgical resection. Electrical propagation of seizures via the cingulate gyrus appears to be an alternative mechanism underlying gelastic seizures. PMID- 11198509 TI - Thalidomide therapy in childhood tuberculous menigitis. PMID- 11198510 TI - Is there a treatment for testosterone? PMID- 11198511 TI - Injury to Maori. I: Fatalities. AB - AIMS: Our aim was to determine the significance in Maori of injury in relation to other health problems, to describe the leading causes of injury, and to determine age specific rates for major classes of injury. METHODS: We used New Zealand Health Information Services mortality data files. The New Zealand Census classification of 'Sole-Maori' was used to determine injury mortality rates. RESULTS: For more than three contiguous decades of life (1-34 yrs) injuries were the leading cause of death. For all age groups combined, unintentional injury accounted for 75% of injury deaths, suicide 17%, and assault 7%. The leading mechanism of death was motor vehicle traffic crashes (49%). Occupants of motor vehicles accounted for the majority of the victims. The occupant fatality rate remained relatively constant for all age groups from 15-24 years. The second most common mechanism of death was suffocation (13%), 76% of which were self inflicted, all of these being hangings. CONCLUSIONS: There is a need for government agencies with a mandate for injury prevention to develop specific injury prevention goals for Maori. PMID- 11198512 TI - Injury to Maori. II: Serious injury. AB - AIMS: To determine the significance of serious injury in Maori relative to other health problems, to describe the leading causes, and to determine age specific rates for major classes of injury. METHOD: We used New Zealand Health Information Services' public hospital inpatient data files. The New Zealand Census classification of 'Sole-Maori' was used to determine injury mortality rates. RESULTS: On average, one in every eight admissions in Maori, was for injury. Injury was the leading reason for admission for those 5-44 years old. Unintentional injury accounted for 85% of injuries, with those ages 1-14 and 15 24 years having the highest numbers and rates. Falls, followed closely by motor vehicle traffic crashes, were the leading causes, accounting for 23% and 20% respectively. CONCLUSIONS: In order to address the priorities identified here, appropriate partnerships between crown agencies and social agencies, both Iwi and/or community based, must be established. PMID- 11198513 TI - Integrating primary and secondary care: the case of Christchurch South Health Centre. AB - AIMS: To study health services utilisation linkages and methodological issues in integrating primary and secondary care services for a defined general practice population (Christchurch South Health Centre, CSHC). METHODS: The Centre supplied national health index (NHI) linked data on date of birth, gender and community services card (CSC) status for 10,174 patients, and data on primary care. Secondary care providers supplied NHI linked data on specialist outpatients, emergency department usage for 1996 to 1998, and waiting lists. The Health Funding Authority (HFA) supplied NHI linked data on inpatient/daypatients for 1996 and 1997. Data were also obtained relating to community support services and long-term care. Rates of hospital utilisation for the Centre's population were standardised for comparison with national and Christchurch figures using age, gender and CSCs. Overall per capita expenditure was calculated for this population. RESULTS: Patients with CSCs constituted 31.2% of the practice population, but generated 60.8% of bed-days. Patients with high use health cards (HUHCs) constituted 8.6% of the population, but generated 42.4% of bed-days. This group was at high risk of hospitalisation over a wide range of disease categories. Standardised rates of hospital utilisation were significantly lower for the Centre's older patients, especially for bed-days, than both national and Christchurch figures. Only a small proportion of referrals to specialist outpatients, 28.2% in 1998, was from the Centre's general practitioners (GPs), the remainder being generated internally within the specialist services. The overall expenditure per capita on the Centre's population was $1012, which was substantially less than expected in comparison with national figures. CONCLUSION: The study demonstrates the importance of primary care factors in the utilisation of secondary care, especially acute hospitalisation in older patients. This needs further study as it could provide important insights into ways of reducing acute admissions. If there is to be more effective management of the primary/secondary care interface, more research and development effort is needed into the characteristics of patients at high risk of referral and admission, and how inappropriate secondary care can be averted. PMID- 11198514 TI - Variations in self-reported health status: results from a New Zealand survey. AB - AIMS: To report measures of the self-reported health of a sample of the New Zealand adult population elicited using the EuroQol Group's EQ-5D questionnaire, and to investigate variations in these measures, according to respondents' socio demographic characteristics. METHODS: Personal health status questions were included in a self-completed postal questionnaire mailed to a non-stratified sample of 3000 New Zealanders, selected at random from the electoral roll. 1350 questionnaires were completed and returned. Each respondent rated their health on the five EQ-5D dimensions- mobility, self care, usual activities, pain/discomfort and anxiety/depression- and assigned a global score to their profile. RESULTS: Pain/discomfort was the most commonly experienced health problem, with 41% of all respondents and 63% of over-70 year olds reporting moderate or extreme problems. Just 4.5% of respondents reported problems with self-care. Respondents were more likely to report problems on each of the five dimensions and to have a lower global score if they smoked, if they were unemployed, a houseworker or retiree, and if their education did not continue past the minimum school leaving-age, or they did not have a degree or equivalent qualification. Problems on all dimensions were more common the older the respondent, and the global score was lower for over-70 year olds than for younger people. Neither the global score nor the incidence of problems on any of the dimensions was related to sex or ethnicity. CONCLUSIONS: The EQ-5D is a potentially useful instrument for monitoring health in the New Zealand context. Further research to explore its validity and reliability, particularly for Maori, would be valuable. PMID- 11198515 TI - Bilateral femoral artery thrombosis in nephrotic syndrome. PMID- 11198516 TI - Waikato mental health service reorganisation: a model to reduce bed needs? PMID- 11198517 TI - Radiation protection for health care workers. PMID- 11198518 TI - Doctor global is unethical and dangerous. PMID- 11198519 TI - Green Prescriptions doing well. PMID- 11198520 TI - Stable angina and coronary angioplasty. PMID- 11198521 TI - Quantitative volumetry in patients with carotid disease--effects of acetazolamide. AB - The intracranial effects of acetazolamide on flow velocities can be monitored noninvasively by transcranial Doppler (TCD) sonography. Extracranial volume flow changes can now reliably be measured with color duplex M-mode systems. The authors tested the volumetric effects of acetazolamide in patients with high grade unilateral carotid disease to quantify the amount of flow changes. Patients in group 1 had a high-grade > 70% internal carotid artery (ICA) stenosis, without collateral flow through the ophthalmic artery (OA). Patients with occluded ICA were included in group 2 (patent OA collateralization) or group 3 (no OA collateralization) (n = 6 per group). In group 1, common carotid artery (CCA) volume flow in the stenotic (normal contralateral) side increased from 271 (388) ml/min by 52 (54%) with 1 g aceta-zolamide intravenously. Simultaneously, middle cerebral artery (MCA) flow velocities increased from 54 (56) cm/s by 47 (53%). In group 2, extracranial volume flow increased from 166 (444) ml/min by 19 (52)%. MCA flow velocities increased from 43 (65) cm/s by 13 (30)%. In group 3, volume flow increased from 159 (467) ml/min by 2 (46)%. Intracranial flow velocities rose from 49 (54) cm/s by 27 (41)%. Volume flow data showed the expected decline in patients with high-grade ICA stenosis and even more pronounced in patients with occlusion of the vessel. Cerebral reserve capacity was less sufficient in patients with a patent OA, despite an additional supply of 30 ml/min, indicating a hemodynamically critical situation. PMID- 11198522 TI - Ultrasonic assessment of physiological echo-contrast agent distribution in brain parenchyma with transient response second harmonic imaging. AB - OBJECTIVES: The present study was designed to provide normal data of transient response second harmonic imaging (TRSHI) examinations of cerebral echo contrast enhancement using different modes of electrocardiogram (ECG) gating and echo contrast agent doses. MATERIALS AND METHODS: Fifty-five patients were examined in an axial diencephalic plane of section using the transtemporal acoustic bone window. TRSHI examinations (ECG gating: systolic, frame-rate once every 2 cardiac cycles = "basical instrument setting") could be performed in 50 individuals with adequate insonation conditions after application of 4 g of a galactose-based microbubbles suspension in a concentration of 400 mg/ml. For comparison, diastolic ECG gating (20 patients), cardiac-cycle triggering frequency of once every 2 seconds (15 patients), or an echo contrast agent dose of 2 g Levovist (15 patients) were used. Analysis of peak intensities (PIs) and areas under the curve (AUCs) was done in posterior (region of interest [ROI]a) and anterior (ROIb) parts of the thalamus, in the lentiform nucleus (ROIc), and the white matter (ROId). RESULTS: In 41 patients with basical instrument setting, characteristic time intensity curve (TIC) could be detected in all ROIs. In ROIa (90%) and ROIb (82%), focal contrast enhancement was most difficult to visualize, and in ROIc and ROId, characteristic TICs were observable in more than 90% of the examinations. Background subtracted PIs and AUCs were significantly higher in ROIc (mean PI: 12.2 +/- 8 acoustic units [AUs]; mean AUC: 598.8 +/- 451.1 AU x Cardiac cycles), and ROId (11.8 +/- 6.9; 559.2 +/- 404) as compared to ROIa (8.3 +/- 5.2; 368.9 +/- 242.7) and ROIb (7.1 +/- 4.7; 298.2 +/- 199.1) (P < .0001). Values for corresponding examinations with a diastolic ECG gating and a cardiac cycle triggering frequency of once every 2 seconds were not different as compared to the basical instrument setting. A 4 g Levovist dose increased the portion of typical TIC in all ROIs. PI of 4 g examinations were significantly higher in ROId and ROIb as compared to the 2 g examination. CONCLUSION: Our findings indicate that TRSHI allows noninvasive assessment of focal cerebral contrast enhancement in the majority of patients with adequate insonation conditions. This study provides data about normal quantitative and qualitative TRSHI values in patients without cerebrovascular diseases. A dose of 4 g Levovist is recommended in those individuals with inaccurate echo contrast enhancement using the 2 g dose. PMID- 11198523 TI - The use of clinical scales in depicting cerebrovascular complications in bacterial meningitis. AB - To evaluate the utility of different scales for clinical assessment, over time, in acute bacterial meningitis, the authors investigated 53 consecutive patients (mean age 53 +/- 17 years). Clinical status on days 1, 3, 5, 8, and 14 after admission was determined by the Scandinavian Stroke Scale (SSS), Glasgow Coma Scale (GCS), and Hunt and Hess Scale (HH), and, on day 21, by the Glasgow Outcome Scale (GOS). Transcranial Doppler examinations were performed serially to assess for disease-related arterial narrowing. This was observed in 27 patients (51%) within 2 weeks of admission. All scales were observed to correlate with the 21 day GOS. Patients with cerebral arterial narrowing had significantly decreased SSS scores between days 1 and 8 and worse GCS and HH scores between days 3 and 5. Mean blood flow velocity in the middle cerebral artery on days 5 and 8 significantly correlated with GOS (r = 0.268, P < .008; r = -0.324, P < .003, respectively). The use of such clinical scales allows standardized assessment of patients with bacterial meningitis and provides prognostic information. Cerebral arterial narrowing was observed to correlate with neurologic impairment. PMID- 11198524 TI - Modeling of receptor ligand data in PET and SPECT imaging: a review of major approaches. AB - Over the past decade, a number of new kinetic modeling techniques have been developed for PET and SPECT ligands. This article will review commonly used modeling solutions for reversible positron-emission tomography (PET) and single photon emission computed tomography (SPECT) radioligands, with an emphasis on noninvasive methods. All of the modeling approaches in PET and SPECT assume a compartmental system and derive parameters that describe the compartmental system. These parameters will be defined, and their relationship to analogous parameters in pharmacology will be discussed. Then the major approaches are presented under the categories of graphical or mathematical as well as invasive or noninvasive. PMID- 11198525 TI - Poor prognosis of acute stroke patients denied thrombolysis due to early CT findings. AB - OBJECTIVES: Whether acute stroke patients with major early infarct signs on computed tomography (CT) should be treated with intravenous (i.v.) thrombolysis remains controversial. The authors sought to define the outcomes in 5 consecutive patients who were not treated with i.v. thrombolysis, according to established guidelines. METHODS: The authors retrospectively analyzed the outcomes of a consecutive series of 5 patients evaluated by an acute stroke team at a university medical center and who were denied i.v. tissue plasminogen activator due to early CT changes. RESULTS: Five patients with a median National Institutes of Health Stroke Scale score of 22 (range 20-28) were evaluated. Despite aggressive care (e.g., hemicraniectomy), 2 patients died owing to herniation, 1 patient died of cardiac causes, and neither of the 2 surviving patients achieved a 3-month Rankin score below 4 (moderately severe disability). CONCLUSIONS: Given the poor prognosis of patients with hemispheric stroke and early CT changes, alternative treatment modalities such as intra-arterial thrombolysis, early hemicraniectomy, and neuroprotective therapy should be vigorously pursued. PMID- 11198526 TI - Localization of clinical syndromes using DWI: two examples of the "capsular" warning syndrome. AB - The capsular warning syndrome (CWS) is a subtype of transient ischemic attack characterized by its recurrent nature, absence of cortical signs, and high probability of early capsular stroke. Currently, standard imaging techniques have identified only internal capsule lesions in this entity. The authors present 2 cases with an otherwise typical CWS in whom a brainstem stroke was detected by diffusion-weighted imaging (DWI). DWI's ability to differentiate between acute and chronic infarcts may assist in more accurate localization of clinical syndromes. PMID- 11198527 TI - Ganglioneurocytoma mimicking a malignant tumor: case report with a literature review of the MRI appearance of neurocytomas and gangliogliomas. AB - A 14-year-old girl presented with symptoms of increased intracranial pressure after her head was squeezed at a party. MRI demonstrated a mass that was hypointense to brain on T1WI and heterogeneous in signal on PD and T2WI; compression of the ventricle, midline shift, and mild ventriculomegaly also were present. Contrast enhancement was extensive and heterogeneous, mimicking a malignant tumor. Neuropathology revealed a ganglioneurocytoma. PMID- 11198528 TI - Vertebral artery dissection in Turner's syndrome: diagnosis by magnetic resonance imaging. AB - Aortic artery dissection is a rare but well-recognized complication of Turner's syndrome. Isolated carotid or vertebral artery dissection has not previously been reported. The authors report the clinical and magnetic resonance imaging findings in a 30-year-old woman with Turner's syndrome who developed a high cervical spinal cord infarction with a Brown-Sequard syndrome owing to bilateral vertebral artery dissection. The diagnosis and management of the case is reviewed. PMID- 11198529 TI - Limbic encephalitis investigated by 18FDG-PET and 3D MRI. AB - Two patients with clinically probable or possible limbic encephalitis (LE) are reported, both cases with typical findings in clinical symptoms (severe neuropsychological deficits and complex partial seizures) and in routine magnetic resonance imaging (MRI) (hyperintense mesiotemporal lesions). Underlying malignancy was identified (rectal carcinoma) in one case but could not be detected in the other patient. The 2 patients were investigated by cerebral 18F fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) and 3-dimensional (3D) MRI, and abnormalities in metabolic activity were mapped using coregistration of spatially normalized PET and MRI. Highly significant focal hypermetabolism in bilateral hippocampal areas was found in both cases. The authors' findings support FDG-PET coregistered to 3D MRI as a potentially valuable additional tool in the imaging diagnostics of LE. Results are discussed with respect to the clinical symptoms and previously reported imaging findings in the disease. PMID- 11198530 TI - Cerebral and oculorhinal manifestations of a limited form of Wegener's granulomatosis with c-ANCA-associated vasculitis. AB - The authors report on cerebral and oculorhinal manifestations in a patient with a cytoplasmic pattern of antineutrophil cytoplasmic autoantibody (c-ANCA) associated vasculitis. Recurrent Tolosa-Hunt syndrome, cavernous sinus syndrome, Raeder's paratrigeminal neuralgia, and seizures were the major clinical manifestations. Brain MRI showed localized enhancing lesions initially in the cavernous sinus and later in the convexity pachymeninges. The lesions disappeared following 9 months of oral prednisolone (15 mg/day) and cyclophosphamide (100 mg/day) therapy. The presence of c-ANCA, demonstration of vasculitis, and depositions of immunoglobulin G (IgG) and fibrinogen in the vessel walls of pachymeninges of the patient confirmed an immune-mediated cause of the vasculitis. Cranial pathology without renal and pulmonary involvement suggests a variant of Wegener's granulomatosis, which is called the "limited" form of Wegener's granulomatosis. MRI, Raeder's paratrigeminal neuralgia, localized pachymeningitis. PMID- 11198531 TI - Temporal changes in brain volume and cognition in a randomized treatment trial of vascular dementia. AB - OBJECTIVE: To measure changes in brain and ischemic volume over time by magnetic resonance imaging (MRI) as part of a randomized treatment trial of vascular dementia. METHODS: Participants who met criteria for vascular dementia underwent comprehensive neurological and neuropsychological testing on entrance, during, and at completion of the 1-year study. For those centers who had easily available MRI, MRI of the brain was to be performed on entry and completion of the study. Image analysis was performed on all balanced and T2-weighted MR films to determine ventricular, sulcal, ischemic, and hemispheric brain volumes. RESULTS: Of the 105 patients who met the criteria for vascular dementia, 40 had a baseline MRI study that met protocol requirements and was of excellent image quality. The baseline ventricular volume in these 40 patients with high-quality MR correlated with most measures of cognitive and behavioral function, including the total Alzheimer's Disease Assessment Score (ADAS) (r = 0.51, P = .0024), as well as activities of daily living (r = 0.61, P = .0002). The baseline ischemic brain volume correlated well only with the gait and postural stability scale (r = 0.74, P = .009). Of the 40 participants, 25 had MRI studies at baseline and at completion of the study that were comparable and of excellent image quality. For these 25 patients, the mean ventricular volumes increased by 9% over the study year (P = .001) and the mean ischemic brain volume increased by 18% (P = .01). Temporal changes in the sulcal and nonischemic brain volume did not reach significance. None of the 14 clinical score measures changed significantly between baseline and completion of the study in these 25 patients. CONCLUSION: In summary, ventricular volume correlated well with cognitive measures in patients with vascular dementia and was a more sensitive marker for change during the study year than the clinical scales used in this study. This study also points out the practical limitations of brain imaging as a surrogate measure of clinical outcome in multicenter randomized treatment trials of brain disease. PMID- 11198532 TI - Anticoagulation and microembolus detection in a case of internal carotid artery dissection. AB - BACKGROUND: Microembolic signals (MES) have been demonstrated by transcranial Doppler (TCD) in cases of internal carotid artery dissection. The influence of treatment on MES in arterial dissection is uncertain. The authors here present a case of internal carotid artery dissection in which we detected a reduction of MES after the initiation of intravenous heparin. METHODS: A 37-year-old woman developed a right temporal headache 10 days prior to admission. This was followed by episodes of left arm numbness and weakness. Magnetic resonance imaging (MRI) showed a right frontal and deep subcortical ischemic infarct. Catheter angiography confirmed a right internal carotid artery dissection with intracranial extension. She was then monitored with TCD for MES before and after intravenous heparin was started. RESULTS: The first TCD, performed 12 days after symptom onset, showed 39 MES during 60 minutes of insonation of the right middle cerebral artery. Treatment with intravenous heparin resulted in a decline in MES by 50% after 96 hours. This decline continued and no further MES were detected after 11 days of anticoagulation. CONCLUSION: The authors were able to demonstrate a decline of MES with heparin anticoagulation in a case of internal carotid artery dissection. PMID- 11198533 TI - Solitary intramedullary neurosarcoidosis: role of MRI in early detection. AB - BACKGROUND: Intramedullary neurosarcoidosis may be the first manifestation of the disease and may mimic a tumor clinically and radiographically. Two patients who presented with cervical intramedullary lesions on magnetic resonance imaging (MRI) scans were found to have neurosarcoidosis. CLINICAL PRESENTATION: Two patients with negative past medical history presented with progressive myelopathic features, and intramedullary cervical lesions were detected on MRI scan; the diagnosis was made on biopsy of the lesions. Early therapeutic intervention led to a favorable outcome. CONCLUSION: Intra-medullary neurosarcoidosis, especially in the cervical cord, can be the initial presentation of the disease, mimicking a tumor. MRI scan, biopsy, and, in fewer cases, angiotensin-converting enzyme levels can help with the diagnosis and may lead to a favorable outcome. PMID- 11198534 TI - Endovascular treatment of a ruptured dual aperture cavernous aneurysm. AB - The authors describe the diagnosis and endovascular management of a multiaperture, ruptured cavernous internal carotid artery aneurysm causing a carotid cavernous fistula (CCF) using both transarterial and transvenous techniques. Although uncommon, recognition of the imaging characteristics of such a lesion will aide in successful management and improve treatment outcome. To the authors' knowledge, CCF due to a ruptured cavernous aneurysm with multiple shunts has not been previously reported. PMID- 11198535 TI - Extensive subdural mass. AB - An unusual case of a 62-year-old man with focal seizures, tinnitus, and progressive left hemiparesis due to an extensive subdural plasma cell granuloma is presented. Five-year clinical and radiologic follow-up demonstrating the chronic yet progressive nature of this granuloma is presented. This is the first report of focal calcification seen in an intracranial plasma cell granuloma. The imaging, neuropathologic, and clinical characteristics of this rare lesion are reviewed. PMID- 11198536 TI - Continuity of patient care and safety standards. PMID- 11198537 TI - Environmental tobacco smoke: views from the Dunedin hospitality industry on prohibition of smoking in licensed premises. AB - AIMS: To describe Dunedin hospitality industry perceptions of difficulties in enforcement of a prohibition on smoking in licensed premises, and possible effects on staff, customers and business. To identify any need for education to assist transition and reduce compliance difficulties with smoke-free legislation. METHODS: A reply paid questionnaire was mailed to all 311 licensed premises registered with the Dunedin District Licensing Agency, operational in May 1999. RESULTS: overall response rate (67%) differed significantly by type of premises (bar, club, restaurant and off-licence). Overall, a smoking ban was considered likely to be difficult to enforce (82%), upset customers (74%), reduce business (59%) and negatively effect employees (51%). On each issue, there was a consistent pattern of increasing concern from off-licenses (least concern) through restaurants, to clubs and bars (most concern). CONCLUSIONS: Considerable concern exists in the hospitality industry about the effects of extending smoke free status to licensed premises. To assist transition and future compliance, there is a need to address these concerns and provide reliable information to calm unnecessary fears and develop appreciation of the need for change. PMID- 11198538 TI - Promotion of smoking cessation by New Zealand general practitioners: a description of current practice. AB - AIMS: To describe the advice and support New Zealand general practitioners (GPs) reported providing to patients about smoking cessation, to explore barriers encountered in providing this advice, and to compare reported practice with recommended best practice. METHODS: 450 GPs were surveyed from four different localities using a structured postal questionnaire. RESULTS: Questionnaires were returned by 283 GPs, giving a response rate of 63%. Approximately one-third of GPs asked every adult patient about their smoking status. Fewer recorded this information in the patient's notes. GPs, based on their own experience, considered nicotine replacement therapy (NRT) and their own advice to quit to be the two most useful smoking cessation strategies. They perceived patient resistance and time pressures as the main barriers limiting their ability to give advice to patients about smoking cessation. CONCLUSIONS: GPs provide smoking cessation advice to many patients, but this needs to be viewed in the context of the New Zealand fee-for-service primary care system and competing demands placed on the limited time available within a consultation. There is potential to increase the practice nurse's involvement in providing smoking cessation advice. PMID- 11198539 TI - Tuberculosis: reasons for diagnostic delay in Auckland. AB - AIMS: First, to quantify the interval between the onset of symptoms and the start of anti-tuberculous treatment in a series of Auckland tuberculosis patients. Second, to examine the help-seeking behaviour of the patients and the responses of the health-care providers whom they consulted about their symptoms. Third, to identify potentially modifiable reasons for delayed presentation or diagnosis. METHODS: 100 patients with tuberculosis (TB) were interviewed using a questionnaire which sought symptom duration and help-seeking behaviour. The doctors whom they consulted were surveyed about their diagnostic, therapeutic and referral responses. RESULTS: Delayed presentation by patients ('patient delay') was found in smokers, patients who reported cough, patients who hoped their symptoms would go away on their own, and patients reporting fear of what would be found on diagnosis. 'Doctor delay' (the interval from first consultation with a doctor to start of treatment) was longer than that found in most published series and was a more important component of total delay than delayed presentation by patients. Longer doctor delay was found if patients had pre-existing lung disease or consulted multiple doctors, and if doctors did not inquire into past exposure to TB or request a chest X-ray. CONCLUSIONS: Awareness programmes for high-risk communities are needed to encourage early reporting of symptoms. Continuing medical education for general practitioners is needed to encourage vigilance for TB and earlier use of diagnostic tests in patients who have symptoms of TB and are in high-risk groups. PMID- 11198540 TI - Increased mesothelioma incidence in New Zealand: the asbestos-cancer epidemic has started. AB - AIMS: To examine the incidence and mortality patterns for malignant mesothelioma and pleural cancer in New Zealand between 1962-1996, and relate these to past use of asbestos. METHODS: Data concerning cases of mesothelioma 1962-1996, deaths from pleural and lung cancers 1974-1996, and data on imports of raw asbestos and asbestos products were obtained from government registers and publications. Time trends were analysed using different models. RESULTS: Mesothelioma incidence rates have increased progressively in New Zealand since the 1960s, and reached 25 per million for men in 1995. The increase follows an exponential model departing from a crude 'background rate' of 1-2 per million in 1984, and is particularly steep in males 50 to 60 years of age. The incidence is expected to double by 2010. CONCLUSION: New Zealand has entered an unrivalled period of occupational cancer deaths resulting from past workplace exposure to airborne asbestos fibres. The steep rise in mesothelioma incidence is likely to be accompanied by increases in other asbestos related diseases such as lung cancer. The unique causal association between mesothelioma and asbestos may be used to monitor changes in the public health impact of these exposures. The notification by medical practitioners of all potential asbestos related conditions/exposures to the Occupational Safety and Health (OSH) service is of great importance. PMID- 11198541 TI - Occupational asthma cases notified to OSH from 1996 to 1999. AB - AIMS: To update notifications to the Occupational Safety and Health Service of the Department of Labour (OSH) Notifiable Occupational Disease System (NODS) from June 1996 to the beginning of 1999. METHODS: All notifications received for non asbestos related occupational respiratory disease were reviewed to confirm the clinical diagnosis, occupational causation, and to identify the causative agent where possible. RESULTS: 54 cases of asthma were notified, of which 21 (39%) were accepted as being occupationally caused. These cases arose from 'predictable' industries. CONCLUSIONS: NODS offers sentinel data from interested practitioners and workplaces. Occupational asthma and other occupational respiratory diseases remain poorly notified to this system. NODS confirms the presence of occupational asthma in New Zealand from predictable and preventable causes not dissimilar to other countries. This data collection system needs supplementation by other mechanisms. PMID- 11198542 TI - General practitioner management of upper respiratory tract infections: when are antibiotics prescribed? AB - AIM: To assess General Practice (GP) description and management of upper respiratory tract infections (URTI), including conditions under which they prescribe antibiotics. METHOD: A telephone survey of a randomised sample of Auckland GPs. RESULTS: There was a 61% response rate. 82 of the 100 GPs interviewed agreed that most patients presenting with URTI expected antibiotics. Persistent symptoms and indication of specific infection (tonsillitis, otitis media, sinusitis, pharyngitis, purulent sputum) were common reasons for prescribing. Patients travelling overseas, expecting or requesting antibiotics and prior use of over-the-counter (OTC) medications increased antibiotic prescribing-rates. Most GPs (95%) issued as-needed prescriptions on occasion; 13% did this often. Amoxicillin and amoxicillin/clavulanic acid were most commonly used. Despite wide-ranging antibiotic use for URTI (0 to 90%), only 6% of GPs felt they prescribed more antibiotics than others. CONCLUSIONS: The results suggest over-prescription is common-place, but use of as-needed prescriptions to reduce antibiotic use is encouraging. Exploration of patient expectations in the consultation may assist in decreasing prescribing rates. PMID- 11198543 TI - High pharyngeal carriage rates of Streptococcus pyogenes in Dunedin school children with a low incidence of rheumatic fever. AB - AIM: To document the incidence and type distribution of Streptococcus pyogenes in a group of Dunedin children throughout the 1997 school year. METHODS: The 780 children recruited from ten primary schools had their throats swabbed on each reporting of pharyngitis. Additional pharyngeal swabbings were obtained monthly from a representative subset of these children, referred to as group 1. All swab samples were plated on CNA-P, a blood agar medium that facilitates detection of haemolytic streptococci. S. pyogenes isolates were classified according to the RFLP patterns of PCR products of their emm genes (ERP typing). Representative isolates of each ERP pattern were also emm-typed, a sequence typing method that correlates with serological M-typing. RESULTS: 28% of the group 1 children were found to carry S. pyogenes for more than two months. This carriage rate is similar to that previously detected in Dunedin and Waikato schoolchildren, but is higher than that generally reported in other countries. Although the predominant S. pyogenes types detected in Dunedin are similar to those in North Island populations, some of the types frequently associated with North Island cases of rheumatic fever and glomerulonephritis were absent or isolated infrequently from the Dunedin children. CONCLUSION: The high pharyngeal carriage rates of S. pyogenes in Dunedin schoolchildren, without the concomitant increased occurrence of post-streptococcal sequelae observed in North Island populations may, in part, be due to a relatively lower occurrence of the M-types most commonly implicated in these diseases. PMID- 11198544 TI - Home ventilation: the Green Lane Hospital experience. AB - AIMS: To describe the characteristics and outcomes of patients treated with domiciliary nocturnal support ventilation (NSV). METHODS: Case-note review of all patients treated with home NSV by Green Lane Hospital. RESULTS: 111 patients received home NSV between 1990 and 1999. 59 had respiratory failure due to obesity-hypoventilation syndrome (OHS), most of whom were Maori or Pacific Island people. Their mean BMI was 53 kg/m2. They frequently presented acutely, and often in extremis. After a median duration of 22 months treatment, 37 patients continued treatment. Four have died, but none from respiratory failure. Other causes of respiratory failure included: neuromuscular disease (26), kyphoscoliosis (19) and obstructive sleep apnoea (8). Patients who did not have OHS were mostly of New Zealand European ethnicity, required lower ventilation pressures than patients with OHS, and had better arterial blood gases on treatment. After a median follow-up of 35 months, however, fourteen have died. 33 continued on treatment. Both OHS and non-OHS patients had high deprivation scores according to NZdep96. This was most apparent for patients with OHS. CONCLUSIONS: OHS is an important cause of respiratory failure in New Zealand, particularly affecting Maori and Pacific people. The prognosis of OHS treated with NSV appears to be good despite significant co-morbidity. PMID- 11198546 TI - On the temperature dependence of ultrasonic attenuation in human calcaneus. PMID- 11198545 TI - Influenza vaccination coverage in Canterbury rest homes. AB - AIMS: First, to investigate the effect on Canterbury rest home residents of national policy making influenza vaccination free for those aged 65 years and over. Second, to assess rest home staff influenza vaccination coverage. METHODS: A comparison of influenza vaccination coverage in Canterbury rest home residents during 1996 and 1997 was conducted. Subgroups of rest homes were formed in 1997 to minimise the bias introduced through conducting a coverage survey in 1996. Staff vaccination coverage was also assessed in 1997. RESULTS: Influenza vaccination coverage of Canterbury rest home residents was 74% in 1996 and 76% in 1997. Staff vaccination coverage was 21% in 1997. Significantly more staff were vaccinated in rest homes that offered free influenza vaccination to their staff. CONCLUSIONS: The free influenza vaccination policy had no measurable impact on Canterbury rest home residents' vaccination coverage. This may be due to a ceiling effect of previously high coverage. Coverage was low amongst rest home staff. Providing the vaccination free of charge might improve staff coverage. PMID- 11198548 TI - Presidential address. The Ministry of Health. PMID- 11198547 TI - Which should be the role of bone ultrasonography in the therapeutic follow-up of postmenopausal osteoporosis? PMID- 11198549 TI - Address to open the Biennial Conference of the New Zealand Dental Association, Dunedin, 4 October 2000. PMID- 11198550 TI - Clinical anxieties among dental students. AB - We analysed the perceived stresses associated with the transition from preclinical to clinical teaching among dental students at the Faculty of Dentistry, University of Otago. An anxiety questionnaire was completed by 120 students in their Second and Third Years of study. Because of the institution of a new curriculum, these students were uniquely in the same class. The highest levels of anxiety associated with general clinical situations were felt for getting diagnoses wrong, hurting patients, dealing with medical emergencies, and getting infected. In general, there were no significant gender or academic year differences. When faced with specific situations, students were most stressed by the prospect of surgical procedures, temporomandibular joint problems, and failed local analgesia. Significant differences between the two years centred on giving an inferior alveolar nerve block and in dealing with poor oral hygiene, the Second-year students showing the greater anxiety. PMID- 11198551 TI - Leukaemia in children. Part II--Dental care of the leukaemic child, including management of oral side effects of cancer treatment. AB - The treatment of a leukaemic child requires a multidisciplinary approach. The dental team should provide interceptive and preventive measures prior to the commencement of therapy whenever possible. During therapy, preventive and palliative measures are essential. Once remission is achieved, the child continues to have increased dental needs due to the effects of treatment. These needs may include an increased caries rate, dental maldevelopment, and secondary malignancy. PMID- 11198552 TI - Oranga niho. PMID- 11198553 TI - [Cost effectiveness of bisoprolol in treatment of heart failure in Germany. An analysis based on the CIBIS-II study]. AB - OBJECTIVES: Economic analysis of bisoprolol plus standard therapy versus placebo plus standard therapy in the treatment of chronic heart failure in Germany. MATERIALS AND METHODS: Prospective analysis of resource use and costs by way of integration into the international, randomized, double-blind CIBIS (Cardiac Insufficiency Bisoprolol Study)-II clinical trial, which treated 1,327 patients with bisoprolol and 1,320 with placebo. Two hundred and fifteen German patients were included in CIBIS-II (bisoprolol: 112, placebo: 103). The German health economic subpopulation comprised 97 patients (bisoprolol: 52, placebo: 45). The economic base analysis valued the resource use of every single patient of this subpopulation in monetary terms, from the perspective of Germany's third party payer (statutory sick funds). RESULTS: Mean observation time was 1.3 years. During this time hospitalization costs of DM 783.--were saved in the bisoprolol group. Total direct medical costs amounted to DM 7,651.--in the bisoprolol group and DM 8,905.--in the placebo group. This means savings of DM 1,254.--per patient, or a 14.1% cost reduction. If mean data of all German CIBIS-II patients are used as a broader basis, bisoprolol therapy saves DM 1,203.--per patient. Bisoprolol therapy induced a mortality rate reduction from 17% to 12% in the overall clinical CIBIS-II population (n = 2,647). This difference is statistically highly significant (p < 0.0001). Altogether 74 lives could be saved by bisoprolol therapy. Saved life years amounted to 0.03 per patient after 65 weeks of therapy (460 days), and to 0.12 per patient after 130 weeks (30 months). As bisoprolol therapy leads to net savings, a formal cost-effectiveness analysis, which would relate incremental clinical efficiency to additional costs, is not needed. CONCLUSION: The use of bisoprolol in the therapy of chronic heart failure is not only clinically effective, it also saves net costs. PMID- 11198554 TI - [Risk factors and surgery rates in gallstones. Results of a population-based study]. AB - STUDY OBJECTIVE: The prevalence of gallstone disease, time trends in the frequency of cholecystectomies and risk factors for the occurrence of cholelithiasis were examined in a cross-sectional population study. METHODS: The survey was based on a random sample from the populations of 4 regions in Germany, stratified by region, age and sex. Information on the frequency of gallstone disease and on potential risk factors were collected by standardized interviews. For the statistical analysis, multiple logistic regression was used. RESULTS: Overall, 1,085 persons were interviewed. The age-standardized prevalence of known gallstones was 4.2% for men and 14.5% for women. The frequency of cholecystectomy almost tripled in women from 1985 to 1994 as compared to 1975 to 1984 despite a decreasing trend in gallstone diagnoses in the same time period. No such trend was apparent in men. In men, age, body weight, changes in body weight, diabetes and use of corticosteroids were identified as risk factors for gallstone disease. In women, gallstone disease was also associated with body weight, changes in body weight and age, and, in addition, the number of births. An inverse association with gallstone disease was found for use of oral contraceptives and level of education in women. PMID- 11198555 TI - [Prevention of infection with Streptococcus pneumoniae]. AB - Streptococcus pneumoniae is the most common etiologic agent in outpatients pneumonia. Pneumococcal infections are often associated with high mortality risk in immunocompromised patients. An increasing resistance of Streptococcus pneumoniae to antibiotics is observed worldwide. This led to the official recommendation by the STIKO to use the vaccination in special risk groups. The commercially available 23-valent polysaccharide vaccine produces a reliable immune response against pneumococcal infection in children aged over 2 years and adults. The recommendation should be more realized in practice. PMID- 11198556 TI - [Renin-angiotensin-aldosterone system and fibrinolysis]. AB - Experimental, genetic and clinical evidence suggests that the renin-angiotensin aldosterone system (RAAS) may participate in the pathogenesis of thromboembolic cardiovascular disorders such as coronary heart disease. This interrelationship may involve mechanisms other than changes in arterial blood pressure. In addition to various possible interactions, accumulating evidence suggests that the RAAS is involved in the regulation of the fibrinolytic system. Several recent studies have shown that stimulation of the RAAS may be associated with an activation of plasminogen activator inhibitor 1 (PAI-1). Since profibrinolytic factors (especially tissue plasminogen activator [t-PA]) remain unchanged, increased activity of the RAAS may thus alter the fibrinolytic balance towards a decreased fibrinolytic activity. These findings may be of special importance for a variety of clinical problems such as the long-term effect of a low NaCl-intake on cardiovascular morbidity and mortality and the possible value of drugs indirectly or directly interfering with the RAAS such as diuretics, ACE-inhibitors and angiotensin II Type 1 (AT1) receptor antagonists. PMID- 11198557 TI - [Mitochondrial medicine for internists]. AB - Human mitochondrial DNA (mtDNA) is a small, circular molecule, encoding for the translational machinery of the mitochondrion, as well as for 13 structural proteins that are all subunits of the respiratory chain. Point mutations, deletions, and copy-number variations are now functionally and genetically linked to human disease. Despite the fact that mtDNA is solely transmitted from the mother to the offspring, e.g. is maternally inherited, some mutations may occur spontaneously or may be acquired due to defects in nuclear DNA, e.g. are inherited in a mendelian fashion. The internist encounters predominantly myopathies, cardiomyopathies, lactic acidosis or diabetes mellitus but mtDNA changes are also present with neurologic, hematologic and renal symptoms. Acquired mtDNA alterations are responsible for important drug side effects, such as ifosfamide, carboplatin, doxorubicin or nucleoside-analog reverse transcriptase inhibitors. A specific mtDNA point-mutation predisposes to aminoglycoside-induced sensorineural deafness. PMID- 11198558 TI - [Cystic fibrosis--initial diagnosis in a 39-year-old patient]. AB - BACKGROUND: Cystic fibrosis is the most common hereditary disorder among Caucasians. Most of the patients are diagnosed as children. However, some cases are going undiagnosed into adulthood and are then often misdiagnosed because the non-pediatricians do not know cystic fibrosis very well and do not consider this diagnosis in adult patients. CASE REPORT: We present the medical history of a woman, who was diagnosed with cystic fibrosis at the age of 39 years, although she had suffered from bronchiectasis, pancreatic insufficiency and liver cirrhosis since many years. Her medical history was long with some diagnosis, but because of her age nobody considered the final diagnosis. CONCLUSION: In adult patients with bronchiectasis, liver cirrhosis and pancreatic insufficiency in combination or with only one of these symptoms, cystic fibrosis should be included into the differential diagnosis. PMID- 11198559 TI - [Isolated ACTH deficiency as a rare cause of recurrent syncope and hypoglycemia]. AB - HISTORY AND CLINICAL FINDINGS: A 63-year-old man was assigned into emergency room presenting with an acute syncope associated with hypoglycemia and hypotension. Clinical findings showed a pale, waxing-colored skin and a disorder of impulse. During the clinical stay the patient's behavior was slowed down and adynamic. INVESTIGATIONS: After exclusion of cardiovascular and neurologic disorders as reason for the repeated syncopes a detailed endocrine diagnostic screening was performed, which revealed a deficiency of cortisol with missing increase of cortisol in the ACTH stimulation test. The ACTH-GnRH-TRH test showed an isolated deficiency of corticotropic hormones. Stimulation with CRH revealed no increase of ACTH or cortisol. Insulin tolerance test revealed an isolated ACTH insufficiency with consecutive deficit of cortisol. A tumor of the adrenal gland was excluded by abdominal scan. Cerebral CT was inconspicuous. Cerebral NMR was suspicious of volume deficiency of the hypophysis. TREATMENT AND COURSE: Under therapy with hydrocortisone 20 mg and fludrocortisone 0.05 mg orally the clinical symptoms of the patient improved impressively. The patient became efficient and dynamic. Systolic blood pressure increased in mean over 120 mm Hg. There were no more hypoglycemic episodes. CONCLUSION: Secondary insufficiency of the adrenal gland should be considered as a rare cause of hypoglycemia if combined with hypotensive circulatory disturbance and missing pigmentation of the skin. PMID- 11198560 TI - [Remission of nocturnal pathological respiratory patterns after orthotopic heart transplantation. A case report and overview of current status of therapy]. AB - BACKGROUND: Cheyne-Stokes respiration is characterized by recurrent phases of central apneas during sleep alternating with a crescendo-decrescendo hyperventilation. This abnormal respiratory pattern is often observed in patients with severe congestive heart failure and associated with fragmentation of sleep, excessive daytime sleepiness, and a relatively high mortality. Increased peripheral and central chemosensitivity, prolonged circulation time, and reduced blood gas buffering capacity are the major factors contributing to the pathology. However, the exact pathophysiologic mechanisms are not clear yet. Respiratory stimulants, oxygen and continuous or bilevel positive airway pressure (CPAP or BiPAP) might reduce the severity of Cheyne-Stokes respiration but have little effect on daytime sleepiness and cardiac function. There is only limited data supporting the assumption that intensive heart failure therapy has an effect on Cheyne-Stokes respiration. CASE REPORT: A 55-year-old male patient with dilative cardiomyopathy (NYHA IV) suffered excessive daytime sleepiness (Epworth Sleepiness Scale: 24 points). The patient was a heavy snorer with a normal body mass index. Treatment was initiated including ACE-inhibitors, beta-receptor blockers, diuretics and digoxin. The patient underwent sleep analysis with a Somno-Check system which demonstrated Cheyne-Stokes breathing (Respiratory Disturbance Index RDI: 40/h, lowest desaturation 76%) and body position dependent snoring. Oxygen therapy (21/min) had no effect on daytime sleepiness. Due to the cardiac condition, the patient was accepted for heart transplantation. Three weeks after transplantation sleep analysis was repeated and demonstrated a lack of evidence for periodic breathing (RDI 1/h, no desaturations below 90%), while snoring remained unchanged. Daytime sleepiness improved significantly (Epworth Sleepiness Scale: 6 points). Three weeks after normalizing left ventricular function a complete recovery from severe Cheyne-Stokes respiration was observed. CONCLUSION: Adequate therapy of the underlying cause of Cheyne-Stokes breathing such as end-stage congestive heart failure might sufficiently abolish any breathing abnormalities. PMID- 11198561 TI - [Egg shell hili in silicosis]. PMID- 11198562 TI - [Euthanasia: spiritual roots in the 19th, crime in the 20th, legalization in the 21st century?]. PMID- 11198563 TI - You don't bring me anything but down: adolescent romance and depression. AB - What accounts for the sex difference in depression that emerges during the period of adolescence? We propose that females become more depressed than males in adolescence partly as a consequence of their involvement in romantic relationships. Using two waves of data from the National Longitudinal Study of Adolescent Health (N = 8,181), a study which began interviewing respondents in 1994, we compare change in levels of depression for adolescents with and without romantic involvement between interviews. Our results suggest that males and females who become romantically involved between interviews experience a larger increase in depression than their counterparts who do not; however, females experience a larger increase in depression than males in response to romantic involvement. Our results suggest that females' greater vulnerability to romantic involvement explains a large part of the emerging sex difference in depression during adolescence. PMID- 11198564 TI - Adolescent cigarette smoking in U.S. racial/ethnic subgroups: findings from the National Education Longitudinal Study. AB - Using nationally representative data for 16,454 8th graders and 13,840 10th graders, we explore racial/ethnic differences in "daily cigarette initiation," beginning to smoke on a daily basis between baseline interviews and reinterviews conducted two years later. In both samples, the initiation rate among whites is more than double the rate among blacks and higher than rates among Asian/Pacific Islanders and Hispanics. Risk factors at the individual, family, and peer-group levels of analysis do not explain most racial/ethnic differences. We develop alternative hypotheses by extending theories of cigarette use to the school level, and we test them using multilevel models: Consistent with social learning theory, cigarette risk among blacks and Hispanics decreases as the percentage of racial/ethnic minority students in the school increases. Consistent with strain theory, cigarette risk increases with the academic competitiveness of the school- especially among females--after controlling for the adolescent's academic performance. PMID- 11198565 TI - Abuse, support, and depression among homeless and runaway adolescents. AB - This study examines the effectiveness of social support networks on psychological well-being among 602 homeless and runaway adolescents. The respondents were interviewed in shelters, drop-in centers, and on the streets in cities of four Midwestern states (Missouri, Iowa, Nebraska, and Kansas). The path model was used to test the direct effect of family abuse and precocious independence on adolescent depressive symptoms and indirect effects through social support networks. Results indicate that although abusive family origins contribute directly to depressive symptoms there are indirect effects of family abuse and early independence through social support networks. Family abuse and early independence drive homeless adolescents to rely on peers for social support. While support from friends on the street reduces depression, association with deviant peers increases depression. PMID- 11198566 TI - Underemployment and depression: longitudinal relationships. AB - We conceptualize employment status not as a dichotomy of working versus not working but as a continuum ranging from adequate employment to inadequate employment (involuntary part-time or low wage) to unemployment. Will shifts from adequate to inadequate employment increase depression as do shifts from employment to unemployment, and to what extent does prior depression select workers into such adverse employment change? We analyze panel data from the National Longitudinal Survey of Youth for the years 1992-1994 for the 5,113 respondents who were adequately employed in 1992. Controlling for prior depression, both types of adverse employment change resulted in similar, significant increases in depression. These direct effects persisted despite inclusion of such potential mediators as changes in income, job satisfaction, and marital status. Marital status buffered the depressive effect of both types of adverse change, but education and job dissatisfaction amplified the effect of unemployment on depression. Prior depression did not predict higher risk of becoming inadequately employed but did predict increased risk of unemployment, particularly for those with less education. These results confirm that both unemployment and inadequate employment affect mental health, and they invite greater efforts to monitor the extent and impact of underemployment. PMID- 11198567 TI - Age, debt and anxiety. AB - What is the association between debt and anxiety? Is the relationship between age and anxiety in part due to financial debt? Recently there has been a renewed interest for the reconceptualization and measurement of socioeconomic status that moves beyond the standard education, occupation, and income. This paper uses credit card debt and stress regarding debt to examine the relationship among age, debt, and anxiety. Using data from a 1997 representative sample of more than 1,000 adults in Ohio, results show that anxiety does increase with the ratio of credit card debt to income, and with being in default; but credit card debt accounts for little of the age-anxiety association. Stress regarding overall debt does explain some of the age effect. In addition, stress also explains some of the effect of the credit card debt to income ratio, and all of the effect of default on anxiety. PMID- 11198568 TI - Marital trajectories and mental health. AB - This study expands the marital status and mental health literature by examining several dimensions of marital trajectories, including the number and type of prior marital losses and duration in current status. Data are drawn from the Piedmont Health Survey of the National Institute of Mental Health Epidemiologic Catchment Area Study, collected in 1982-83 (n = 2,158). Results indicate that number of prior losses moderates the health-enhancing effect of being currently married; higher order marriages are associated with worse mental health. Although results vary across the mental illnesses examined (depression, anxiety, and substance use), the negative effect of multiple loss also is observed for the currently divorced and widowed. There is less evidence that the type of prior loss (i.e., divorce or widowhood) moderates the effect of current marital status on mental health; however, some support is found among the presently widowed. The analyses of duration in current status suggest that the rate of decline in symptoms of anxiety following one's most recent loss varies by marital history among the currently widowed. PMID- 11198569 TI - A cross-national examination of the determinants of self-assessed health. AB - Self-assessed health measures are often utilized in surveys of older adults, and these have been found to be powerful predictors of other health indicators and future health. However, there is still much that is puzzling about the measure. Few studies use comparative techniques to ascertain the determinants of self assessed health across diverse settings. Using recent data from the Philippines, Taiwan, and Thailand, the current study tests whether determinants of self assessed health are similar across samples and whether there are distinct country effects acting upon the association. Ordered probit models reveal that, on the one hand, the determinants of self-assessed health are relatively similar across the three countries, while, on the other, the overall probabilities of reporting favorable self-assessed health remain differentiated even when controlling for a broad series of determinants. The results suggest that cultural variation in the interpretation of health may be a factor and that more subtle measures should be included in future studies of this nature. PMID- 11198570 TI - Emerging therapies for hepatitis C virus (HCV) infection: the importance of HCV genotype. PMID- 11198571 TI - Phaeochromocytomas discovered during coronial autopsies in Sydney, Melbourne and Auckland. AB - BACKGROUND: The diagnosis of phaeochromocytoma can be difficult and previous autopsy studies have found that many of these tumours are not recognised during life. AIM: To determine the incidence of phaeochromocytoma during coronial autopsies and the characteristics of the individuals concerned. METHOD: Review of coronial autopsy records from Auckland (1981-97), Melbourne (1991-97) and Sydney (1991-97). RESULTS: Twenty-two patients were found giving an incidence of 0.05% (one tumour per 2031 autopsies) with similar figures in each centre. Thirteen of the patients were men, 12 were overweight (body mass index >25 kg/m2) and three of the seven Auckland patients were Maori. Fourteen of the tumours were left sided, one was extra-adrenal and none had metastasised. The one patient with bilateral tumours had multiple endocrine neoplasia syndrome type 2 (MEN-2) which had not been recognised during life. The heart weight was increased in 95% of the patients. The tumour may have contributed to the patient's death in up to 50% of the cases, although the true significance of these lesions as a cause of death remains unclear. Three patients died soon after general anaesthetics had been given for unrelated reasons. CONCLUSIONS: Even though phaeochromocytomas are uncommon, we fail to diagnose a significant number of these tumours during life. Methods are needed to increase the detection of phaeochromocytoma and to distinguish functional and non-functional tumours. PMID- 11198572 TI - A multivariate analysis of the association between social class of origin and current social class with self-rated general health and psychological health among 16-year-old Australians. AB - BACKGROUND: A recent review of international literature concludes that there is a relative absence of social class differentials in health in early youth. There is an absence of Australian studies on the effect of social class on the health of this age group. AIMS: To examine the association between social class and health among 16-year-old Australians. METHODS: The data on 1048 16-year-olds came from the fifth wave (1993) of the Australian Youth Survey conducted by the former Department of Employment, Education and Training. Outcome measures were self rated general health and psychological health (GHQ-12). Binary logistic regression was used to analyse data. RESULTS: Neither social class of origin nor current social class was associated with self-rated general health or psychological health. CONCLUSION: The argument that social class inequalities in health exist in childhood, disappear during early youth, and reappear later appears to hold ground within the Australian context. PMID- 11198573 TI - Cost-effectiveness and accuracy of exercise stress echocardiography in the non invasive diagnosis of coronary heart disease. AB - BACKGROUND: Exercise stress echocardiography (ESE) is a more recent form of totally non-invasive stress testing which like exercise thallium SPECT scintigraphy (ETS) was developed to overcome the known limitations of ECG stress testing, namely the limited diagnostic accuracy and the inability of ECG stress testing to site the region of coronary artery disease (CAD) induced ischaemia. AIMS: To determine the sensitivity and specificity (and overall accuracy) of ESE in a group of patients referred for ETS imaging and compare the relative costs of each technique. METHODS: One hundred and fifteen patients referred for ETS consented to a simultaneous ESE. Of this group, 59 patients underwent coronary angiography which was utilised as the gold standard. RESULTS: The feasibility of ESE was 97% (112 of 115 patients of the total study population and 57 of the 59 patients who underwent coronary angiography). Of the 59 patients undergoing coronary angiography, the sensitivity of ESE and ETS were not significantly different (84.1% versus 91.3% respectively). However, despite the apparent marked difference in specificity (92.3% versus 61.5% respectively), p = NS (Fisher's exact test) as there were only 13 normals in the group who underwent coronary angiography. Overall accuracy was also closely similar (86.0% versus 84.7% respectively) and therefore also not significantly different. By contrast, agreement with coronary angiography as measured by the kappa statistic (kappa +/- SEk) was good for ESE (0.66 +/- 0.11) but only moderate for ETS (0.54 +/- 0.13). Moreover, there was a cost saving of at least $594.00 per patient in favour of ESE. CONCLUSION: ESE is a totally non-invasive, sensitive, specific and cost effective imaging modality for the detection and localisation of CAD. PMID- 11198575 TI - Multiple endocrine neoplasia. PMID- 11198574 TI - A serological re-evaluation of acute non-A non-B hepatitis from the early 1970s. AB - BACKGROUND: The epidemiology and natural history of recently discovered viruses, which may be responsible for cases of seronegative infectious hepatitis, are currently being investigated. Retrospective studies of stored sera can provide a historical perspective of these infections. AIMS: To re-evaluate the serological, demographic and clinical characteristics of patients hospitalised in the early 1970s with acute hepatitis. METHODS: The stored sera of 57 patients hospitalised between 1971 and 1974 with acute hepatitis, designated at that time as non-A non B (NANB) hepatitis, were re-tested using commercially available enzyme-linked immunosorbent assays (ELISAs) for the presence of anti-hepatitis A virus (HAV) IgM, hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) IgG, and anti-hepatitis E virus (HEV) IgG. Stored sera from a group of 57 patients concurrently hospitalised for other conditions were also tested. Detailed records of the original epidemiological interviews were examined to compare patient demographics, risk factors for infectious hepatitis and clinical data for the NANB hepatitis group and an original control group of 604 hospitalised patients. RESULTS: Serum from 15 of the 57 (26%) previously designated NANB hepatitis cases had elevated anti-HAV IgM and are likely to represent missed cases of hepatitis A. Thirteen (23%) of cases previously designated as NANB hepatitis had positive hepatitis C antibody tests. These patients were younger and significantly more likely to have used intravenous drugs than control patients. Three NANB hepatitis and two hospital control patients were anti-HEV IgG antibody positive. All of these individuals were born in, or had travelled to, developing countries. Serum from 27 (47%) of the NANB hepatitis patients were negative on all tests. These hepatitis non-A-E cases included children and elderly adults, but as a group were significantly more likely to have used intravenous drugs than hospitalised control patients. CONCLUSION: Both HCV and probable non-A-E virus(es) were important causes of acute NANB hepatitis during the early 1970s. PMID- 11198576 TI - The value of evidence-based medicine to consultant physicians. PMID- 11198577 TI - The clinical significance of antiphospholipid antibodies in patients without autoimmune disease. PMID- 11198578 TI - Atherosclerosis and the vulnerable plaque--imaging: Part II. PMID- 11198579 TI - Mycophenolate mofetil for treatment of refractory lupus nephritis: four pilot cases. PMID- 11198580 TI - Do we need a new word for patients? PMID- 11198581 TI - Requirements for a biotechnology future: the current position of Australia and the United Kingdom. PMID- 11198582 TI - Leptomeningeal metastases from anaplastic thyroid carcinoma. PMID- 11198583 TI - Left main coronary artery dissection during coronary angioplasty or angiography treated by stent insertion without requirement for emergency bypass graft surgery. PMID- 11198584 TI - Alternating two finger tapping as part of the neurological motor examination. PMID- 11198585 TI - Factitious haemoptysis. PMID- 11198586 TI - Multiple organ failure and pantoprazole. PMID- 11198587 TI - Hypothyroidism--an unusual cause of cardiac tamponade. PMID- 11198588 TI - Lymphoproliferative disease causing angioedema--an uncommon association. PMID- 11198589 TI - Visual loss as the presenting feature of giant cell arteritis. PMID- 11198590 TI - Extensive jugular and upper limb thrombosis in a patient with factor V Leiden mutation and non-Hodgkin's lymphoma. PMID- 11198591 TI - Silent myocardial ischaemia following methysergide overdose. PMID- 11198592 TI - 'A touch of sugar'--a dangerous euphemism still alive and well. PMID- 11198593 TI - Successful renal transplantation in children under 6 years of age. AB - To evaluate the efficacy of renal transplantation in small pediatric patients, we have reviewed 41 allografts performed in 39 children (28 M/11 F) less than 6 years of age between 1987 and 1998 in the North Italy Transplant Program. Of these patients, 39 had a cadaver donor and 2 a living-related donor, with ages ranging from 20 days to 35 years. The mean follow-up was 56 months. Graft survival was 74.5% and 70.5% at 1 and 5 years, respectively. The causes of graft lost were acute rejection (4), graft vascular thrombosis (4), and hemolytic uremic syndrome recurrence (1). Only 1 patient has died due to chickenpox. Double and triple immunosuppressive therapies were used in 63% and 37% of patients, respectively, on the basis of different center protocols, without differences in graft survival. Steroids were successfully administered on alternate days in 37% of patients, 6-12 months after transplantation. Thrombosis was reported in 2 of 6 kidneys from donors less than 1 year of age and in 2 of 35 donors older than 1 year (P < 0.05). Thirty rejections occurred in 23 patients: 7 episodes were steroid resistant and were treated with ATG/OKT3. Thirty-four infections were reported in 16 of 41 patients; of these 17 were viral, 14 bacterial, and 3 due to Mycoplasma. Four surgical complications were reported: 1 graft artery stenosis, 1 ureteral stenosis, 1 urinary leak, and 1 lymphocele. Mean height standard deviation score improved from -2.0 +/- 1.3 pre transplantation to -1.8 +/- 1.4, 1.5 +/- 1.3, and -1.5 +/- 1.5 at 1, 2, and 5 years post transplantation. Linear growth was significantly better in infants treated with alternate-day steroids. Hypertension was a frequent complication, since 19 of the 30 patients with a 5 year follow-up were still being treated with antihypertensive drugs. In conclusion, graft survival in patients less than 6 years old is satisfactory and similar to that obtained in children aged from 6 to 18 years (70.5% vs. 78.9% at 5 years, P = NS). Consequently, since there are many difficulties in managing infants on maintenance dialysis, an early transplant should be considered. Donors older than 24 months carry a low risk of vascular thrombosis and may be successfully grafted in infants. PMID- 11198594 TI - Chronic renal insufficiency from infancy to adulthood. PMID- 11198595 TI - Low serial serum neopterin does not predict low risk for chronic renal graft rejection. AB - Research has provided new and potent immunosuppressants which can potentially stop ongoing rejection. Subclinical rejection is a particular problem in the pediatric age group and early identification of children at risk is of the utmost importance. Neopterin has been previously shown to be a non-specific but sensitive marker for immunologic activity. In this study we hypothesized that low serum neopterin in the 1st year after transplantation predicts a low risk of chronic rejection. We retrospectively analyzed serial neopterin data obtained beyond the early postoperative period in 21 children and correlated the peak and average with glomerular filtration rate (GFR) loss during the subsequent years (P = 0.63, NS, r = 0.10). Our results show that serum neopterin did not differ between the majority of children who developed chronic transplant dysfunction and children with stable transplant function beyond the early post-transplant period. Thus serum neopterin failed to delineate a low-risk population who might be spared more invasive diagnostic procedures such as protocol biopsy. PMID- 11198596 TI - Non-invasive intravascular monitoring in the pediatric hemodialysis population. AB - Assessment of dry weight in pediatric hemodialysis (HD) patients is difficult, since small fluid shifts may result in dialysis-associated morbidity (DAM) and children may not verbalize complaints. Achieving dry weight is critical since chronic fluid overload can result in hypertension and left ventricular hypertrophy. To determine if non-invasive monitoring of hematocrit (NIVM) is useful in preventing DAM in pediatric HD patients, we reviewed 200 HD treatments performed with or without NIVM (no NIVM). DAM was defined as an "event" (e.g., hypotension, headache, cramping) that required nursing intervention. Patient age, weight, and gender were similar in both groups. Desired ultrafiltration was obtained in both groups. The event rate was lower in NIVM than no NIVM for all treatments (0.22 vs. 0.3, P = 0.07) and significantly lower in patients < 35 kg (0.25 vs. 0.47, P = 0.01). The second event rate (fraction of treatments with one event that had a subsequent event occurring at least 15 min later) was lower with NIVM (P < 0.01). For the NIVM group, events in the first 90 min occurred when blood volume changed > 8% per hour; 71% of events (43/60) at 90-240 min occurred when blood volume changed > 4% per hour. NIVM decreases DAM in pediatric HD patients, especially those < 35 kg. Ultrafiltration with blood volume change < 8% per hour is safe in the 1st h and < 4% after 1 h reduces DAM in children. PMID- 11198597 TI - Monitoring cardiovascular changes during hemodialysis in children. AB - Hemodialysis (HD) causes rapid volume shifts and circulatory changes. In chronic renal failure (CRF) Na+/K+ATP-ase is depressed, whereas endogenous digoxin-like factor (EDLF) is elevated. Our aim was to characterize HD-induced cardiovascular adaptation and its possible links to Na+/K+ATP-ase and EDLF. Eleven children with CRF on HD (aged 14.7 +/- 3.7 years) and 11 healthy children were investigated for basic circulatory parameters. Thoracic impedance (Zo) and circulatory parameters were monitored by impedance cardiography (ICG) during HD. Erythrocyte Na+/K+ATP ase and EDLF were measured before and after HD. Up to the loss of 6% of total body weight, Zo rose linearly with fluid removal, above this no further increase occurred. Heart rate and mean arterial pressure (MAP) were inversely related (r = -0.97); MAP rose in the first and decreased in the second part of HD. Systemic vascular resistance paralleled MAP, whereas stroke volume rapidly decreased, but stabilized in the second part of HD. The ratio of preejection period/ventricular ejection time (PEP/VET) correlated positively with HD duration (r = 0.92), suggesting diminished cardiac filling. Cardiac index (CI) remained stable. EDLF was high in uremia accompanied by depressed Na+/K+ATP-ase (P < 0.05 and P < 0.01, respectively). Following HD Na+/K+ATP-ase normalized. Correlation between Na+/K+ATP-ase activity and MAP was linear (r = 0.85). In conclusion, ICG during HD provides detailed information concerning circulatory adaptation resulting in stable CI, suggesting that the dialysis-induced hypovolemia is compensated by the centralization of the blood volume. Changes of Na+/K+ATP-ase indicate that dialyzable blood pressure-regulating substance(s) inhibit(s) the pump. However, lack of further correlation between Na+/K+ATP-ase, EDLF, and cardiovascular parameters indicates the complexity of the regulatory processes. PMID- 11198598 TI - Signs of autonomic neuropathy in childhood uremia. AB - To evaluate the presence of autonomic neuropathy in childhood uremia, cardiovascular autonomic reflexes were examined in children with chronic renal failure. Cardiovascular autonomic reflexes of 10 uremic patients on chronic dialysis and 10 transplanted patients were compared to assess the effect of transplantation on autonomic neuropathy. Resting heart rate, heart rate changes induced by deep breathing, by Valsalva maneuver, and following standing up, and blood pressure change induced by handgrip test were examined. Of the 10 uremic children, 4 showed early involvement and 2 had definite involvement of autonomic neuropathy. Only 1 of the 10 transplanted patients showed early signs of autonomic neuropathy. Autonomic tests demonstrated predominantly parasympathetic dysfunction. In conclusion, cardiovascular autonomic neuropathy is not rare in children and adolescents and young adults with chronic renal failure. In contrast, the prevalence is very low in transplanted patients with similar uremic precedents. Efforts should be made to prevent or delay this uremia-related complication. PMID- 11198599 TI - Intraperitoneal administration of recombinant human growth hormone in children with end-stage renal disease. AB - Recombinant human growth hormone (GH) therapy has been shown to be effective in the treatment of growth failure related to growth hormone resistance among children with chronic renal failure. The traditional route of administration is subcutaneous injection. This study was designed to evaluate the effectiveness and tolerability of intraperitoneal (i.p.) administration of GH in prepubertal peritoneal dialysis patients. Nine subjects were enrolled. Eight completed 24 months of therapy with GH. Baseline height standard deviation scores (SDS) and growth velocity for the prior year were used for comparison. Peak serum GH was achieved 4 h after administration and serum half-life was 4.6 h. Mean height SDS was -3.1 at baseline, -2.5 at 1 year, and -2.3 at 2 years (NS) of GH therapy. Mean height velocity increased from a baseline of 4.6 cm/yr to 8.5 cm/yr in year 1 (P < 0.05) and 6.1 cm/yr in year 2 (NS) of i.p. GH therapy. Peritonitis infection rates were not increased from overall center rates. This research suggests that the intraperitoneal route of administration of GH can be utilized in the treatment of short stature among children requiring maintenance peritoneal dialysis therapy. PMID- 11198600 TI - Fungal peritonitis caused by Curvularia species in a child undergoing peritoneal dialysis. AB - We report the first case of peritonitis caused by Curvularia species in a child undergoing peritoneal dialysis. He presented with gray-black proteinaceous material obstructing the lumen of his Tenckhoff catheter. Although the peritoneal fluid was cloudy, the patient suffered neither significant abdominal tenderness nor systemic symptoms. Catheter removal and treatment with amphotericin B allowed complete recovery and return to peritoneal dialysis within 7 days. Outdoor play in a wooded environment may have allowed contact of this saprophytic fungus with the child's indwelling catheter transfer set. PMID- 11198601 TI - Nephron induction--the epithelial mesenchymal interface revisited. AB - While more and more humoral factors are being implicated in nephrogenesis, there is no detailed knowledge of the morphological structures at the interface of the nephron inducer and the surrounding mesenchyme. Hence we examined this area in the cortex of neonatal rabbit kidneys by scanning and transmission electron microscopy. Our interest was focused on the basal aspect of the collecting duct ampulla and the surrounding competent mesenchyme where morphogenic signals are exchanged during nephron induction. Close contact between these two tissues is assumed during nephrogenesis to allow direct cellular contact or diffusion of soluble factors across a short distance. However, our data show the presence a wide cleft around the collecting duct ampulla spatially separating the inducer and the competent mesenchyme during nephron induction. This cleft is filled with a characteristic fibrillar mesh-work. PMID- 11198602 TI - Two novel alternatively spliced 9-bp exons in the COL4A5 gene. AB - The existence of an alternatively used 18-bp sequence has been described in type IV collagen alpha 5 chain mRNA from human kidney (Guo et al., Kidney Int 44, 1993). In this study we have shown that this sequence is encoded by two exons, termed 41A and 41B, that are located in a 9-kb intron 41 that was sequenced in its entirety. The sequences of exon 41A and 41B were shown to be present in mRNAs from a variety of tissues. PMID- 11198603 TI - Renal dysfunction but not cystic change is ameliorated by neonatal epidermal growth factor in bpk mice. AB - BALB/c mice homozygous for the bpk gene exhibit a form of autosomal recessive (AR) polycystic kidney disease (PKD) with massive collecting duct cysts, common bile duct dilation and chaotic intrahepatic bile ducts/portal triads. The combined renal and biliary pathology mimics much of the pathology seen in human ARPKD. Murine models of ARPKD generally have a reduced renal expression of epidermal growth factor (EGF) and an increased expression of EGF receptors (EGF R). However, the role that EGF and EGF-R play in the progression of PKD has been unclear. Evidence from various model systems/ages of treatment produces conflicting results. Treating neonatal C57BL/6J-cpk mice with EGF ameliorates the renal pathology and dysfunction while treating 2- and 3-week-old bpk mice with an EGF-receptor tyrosine kinase inhibitor also ameliorates ARPKD. Therefore, to determine whether neonatal EGF treatment would accelerate or inhibit the progression of the PKD in bpk mice, we administered exogenous EGF (1 microgram/g body weight subcutaneously) daily from postnatal days 3-9 (a critical period for tubule maturation). Neonatal EGF treatment but not sham treatment retarded the development of azotemia and common bile duct dilation and the chaotic hepatic triad changes in cystic mice. However, EGF treatment neither reduced the severity of the renal cystic pathology nor reduced the degree of cystic enlargement of the kidneys. Cystic mice treated past 9 days of age died prior to their scheduled termination at 21 days of age. The role of EGF in the progression of polycystic kidney disease in bpk mice is relatively complicated, with neonatal treatment being associated with some amelioration of the renal dysfunction and extrarenal pathology without an effect on the renal pathology. Continuation of treatment beyond 9 days increased morbidity. Therefore, in discussing the role of EGF or EGF receptor in mediating the pathophysiology of PKD, the stage of development may be an important consideration. PMID- 11198604 TI - Human T-cell lymphotropic virus-1-associated renal disease in Jamaican children. AB - This report documents the clinicopathological features in two Jamaican children who presented with infective dermatitis, glomerulonephritis, renal failure and human T-cell lymphotropic virus (HTLV-1) seropositivity. Severe hypertension with hypertensive encephalopathy was the most impressive clinical feature. Histological findings from renal biopsy specimens in both cases revealed significant glomerulosclerosis with fibrosis, chronic inflammatory cell infiltrates in the interstitium, and arteriolar hypertensive changes. Membranoproliferative glomerulonephritis (MPGN) was demonstrable in case 1 and marked focal glomerulosclerosis in case 2. Case 1 developed end stage renal failure and died within 3 years of diagnosis. Case 2 remains hypertensive and in chronic renal failure. Although a causal relationship between HTLV-1 infection and renal disease cannot be proven by these two cases, it appears that renal involvement in children with HTLV-1 infection is severe, with the potential for chronic renal failure and malignant hypertension. HTLV-1 nephropathy should be suspected in children with infective dermatitis and renal disease. PMID- 11198605 TI - A survey of pediatric nephrologists on adolescent sexual health. AB - Chronic renal disease often has an adverse effect on adolescent physiologic and psychosocial development. The severity of the disease may necessitate that the pediatric nephrologist be the adolescent's main medical provider and the most available physician to screen for adolescent health risk behaviors. The purpose of this study was to determine pediatric nephrologists' practices of sexual history taking and diagnosis and treatment of sexually transmitted infections in their adolescent patients. A survey was performed on a convenience sample of 66 pediatric nephrologists attending an educational seminar on adolescent care at the 1997 national meeting of the American Society of Pediatric Nephrology. The outcome measures included physicians' reports of interviewing adolescents alone and screening for sexually transmitted infections. Fifty-six percent reported interviewing adolescents alone, 55% routinely ask female adolescents about sexual intercourse (53% ask males) and 10% routinely perform pelvic exams. Current practice in this selected sample of pediatric nephrologists, who by their attendance at the seminar may represent those most motivated to do screening, still leaves adolescents with chronic renal disease potentially at risk for sexually transmitted infections and pregnancy. Educational efforts should be directed at increasing routine confidential sexual history taking for adolescents with chronic renal disease. PMID- 11198606 TI - Sex differences in the renal transforming growth factor-beta 1 system after puberty. AB - Transforming growth factor-beta 1 (TGF-beta 1) has been implicated in many progressive kidney diseases. The present study examines this growth factor during the pubertal and early adult periods. Mixed-sex Munich-Wistar rat kidneys were obtained on selected days of life from birth through 6 months of age. A survey of the TGF-beta 1 system was performed, and then a second experiment focused on cortex and medulla from both sexes at 6 weeks and 16 weeks of age. Reverse transcription polymerase chain reaction for TGF-beta 1 and TGF-beta inducible gene H3 (beta IG-H3) was performed. Active and total levels of protein for TGF beta 1 were isolated from tissue. Active levels of TGF-beta 1 were somewhat lower in older than in younger animals, without sex differences. beta IG-H3 levels were similar. At 16 weeks females had levels of total growth factor approximately threefold greater than males, while adult males appeared to activate the growth factor much more efficiently. These findings suggest that activation of TGF-beta 1 becomes more efficient following puberty in the male rat, while females appear to have reduced activation efficiency compensated by increased total growth factor. These differences may help explain the deterioration at puberty and sexual dimorphism noted with some progressive nephropathies. PMID- 11198607 TI - Recurrence and follow-up after urinary tract infection under the age of 1 year. AB - In order to analyze the risk factors for recurrence and the value of routine follow-up by monthly urine cultures in a group of children who had their first episode of urinary tract infection (UTI) under 1 year of age, we performed a retrospective survey of 262 children (134 girls, 128 boys) who were treated for their first UTI while aged under 1 year in the Department of Pediatrics, University of Oulu, during the years 1978-1984. Detailed data on these children concerning their first and recurrent UTIs were collected from hospital records using a formulated data sheet. Causative bacteria and vesicoureteral reflux (VUR) were analyzed as possible risk factors for recurrent UTI. The time of recurrence and the possible symptoms during the recurrent UTI were also investigated. The follow-up period after the first UTI was 3 years; 35% of the boys and 32% of the girls contracted a recurrent UTI during the 3-year follow-up. In 86% of cases, the first UTI recurrence occurred within 6 months of the primary UTI. Recurrent UTIs were detected significantly earlier with routine monthly follow-up compared with those seeking treatment because of symptoms (log rank test P < 0.01). There was a significant difference in the number of recurrences of UTI according to the grade of VUR (P = 0.006). Recurrence-free survival was shorter and recurrent UTIs occurred more often in the children with grade 3-5 VUR than in those with grade 0 2 VUR (log rank test P = 0.0005). Children without VUR and children with grade 1 2 VUR did not differ in the recurrence rate, and thus grade 1-2 VUR did not increase the risk for recurrent UTI. Monthly routine urine cultures are efficient in detecting recurrent UTI infections in children. Since grade 3-5 VUR is a risk factor both for increased recurrence rate of UTI and for possible subsequent renal damage, these children should be followed with monthly urine cultures for UTI recurrences if not on preventive medication. Since the vast majority of UTI recurrences occur within 6 months of the first UTI, routine follow-up for 6 months seems to be sufficient after symptomatic UTI in children with grade 3-5 VUR. PMID- 11198608 TI - Quantification of proteinuria in children using the urinary protein-osmolality ratio. AB - A prospective study was conducted to determine the correlation of early morning urinary protein/osmolality ratio (mg/l/mosmol/kg) with 24-h urinary protein excretion (mg/m2/day). Study patients consisted of 53 children (aged 1 month to 15 years). Early morning urine samples and 24-h urine samples were collected and analyzed. In group 1 (children without proteinuria), early morning urinary protein/creatinine ratio (Uprot/Ucr, mg/mg) was 0.061 +/- 0.011 and the protein/osmolality ratio (Uprot/Uosm, mg/l/mosmol/kg) was 0.073 +/- 0.014. Twenty four hour urinary protein excretion in group 1 had no significant correlation with Uprot/Ucr or Uprot/Uosm. In group II (children with proteinuria), Uprot/Ucr was 5.78 +/- 1.10 and Uprot/Uosm was 4.42 +/- 1.34. Twenty-four hour urinary protein excretion in group 2 was 1483.6 +/- 303.7 mg/m2/day and its correlation with both Uprot/Uosm and Uprot/Ucr was highly significant (r = 0.87, P < 0.001 and r = 0.88, P < 0.001, respectively). The accepted nephrotic level of proteinuria of 40 mg/m2/h coincides with a Uprot/Uosm ratio of 1.9. In conclusion, early morning urinary Uprot/Uosm is a simple and potentially useful test for 24-h urinary protein excretion, and possibly could be used safely for the assessment of the degree of proteinuria in children. PMID- 11198609 TI - Coccidioidomycosis in adolescents with lupus nephritis. AB - Coccidioidomycosis, a fungal infection endemic in the southwestern United States, can cause life-threatening infections in immunosuppressed patients. We report the contrasting cases of two adolescents with lupus nephritis, treated with intravenous pulse cyclophosphamide and daily oral corticosteroids, who developed pulmonary coccidioidomycosis. One patient developed a fatal form of fulminant disseminated coccidioidomycosis, while the other patient developed a solitary pulmonary Coccidioides immitis abscess which was responsive to intravenous liposomal amphotericin and fluconazole therapy. Because serologies and initial X ray studies can be negative, definitive diagnostic studies including bronchoaveolar lavage and needle aspiration should be performed when there is clinical suspicion of coccidioidomycosis in an immunocompromised patient. Immunosuppressed patients with coccidioidomycosis should receive early intravenous amphotericin therapy and may benefit from long-term suppressive antifungal therapy to prevent relapse. PMID- 11198610 TI - Fatal cytomegalovirus disease in a high-risk renal transplant recipient. AB - The incidence of CMV infection in pediatric renal transplant recipients has increased as immunosuppression levels deepen following the use of newer immunosuppressive agents. It has been thought that 3-5 months of anti-CMV prophylaxis offers sufficient protection for these patients. We present a case of late-onset fatal CMV disease in a pediatric renal transplant recipient who received prolonged anti-CMV prophylaxis while on "quadruple" immunosuppression with daclizumab, mycophenolate, tacrolimus, and prednisone. Our case has prompted us to reassess CMV surveillance, prophylaxis, and immunosuppression levels in our pediatric renal transplant patients. PMID- 11198611 TI - Immunotactoid glomerulopathy in sickle cell anemia. AB - A 12-year-old African American male with homozygous sickle cell disease (SCD) was admitted with insidious onset of periorbital and scrotal edema. The initial evaluation failed to reveal any underlying monoclonal gammopathy, or cryoglobulinemia, or other systemic causes for the renal disease. A percutaneous renal biopsy was consistent with immunotactoid glomerulopathy (ITG), which is rare in children and is characterized histologically by fibrillar deposits in the glomeruli. Children can present with symptoms of nephrotic syndrome and progress to end stage renal disease. Our patient was treated with an ACE inhibitor and is currently free of edema and with normal renal function on follow-up at 1 year. Immunotactoid glomerulopathy should be considered in the differential diagnosis of nephrotic syndrome in children with sickle cell disease. Renal biopsy is indicated in children with sickle cell disease and nephrotic syndrome and ITG should be considered as potential cause. Although there is no effective treatment for this condition, ACE inhibitors can decrease the protein-uria and possibly delay the progression to end stage renal disease. The side effects related to the use of ACE inhibitors should be monitored. These include renal impairment, hyperkalemia, anemia, neutropenia, and angioedema. Since we have a short follow up in our patient, the role and safety of ACE inhibitors in the management of ITG need further evaluation. PMID- 11198612 TI - Treatment of chronic hypertension with intravenous enalaprilat and transdermal clonidine. AB - We report an 11-year-old boy with hypertension and chronic intestinal pseudo obstruction, which renders him totally dependent on parenteral nutrition and prevents the use of oral medications. Here we report the feasibility of utilizing chronic i.v. enalaprilat and transdermal clonidine on a chronic basis to control hypertension. Over the last 10 months, the patient's hypertension has been well controlled by 1.25 mg i.v. enalaprilat every 8 h and a 0.2-mg clonidine patch every 6 days, with no apparent side-effects. There are no reports of i.v. enalaprilat usage exceeding 3 weeks' duration. Therefore we believe that it is possible to effect reasonable management of chronic hypertension with the use of chronic i.v. enalaprilat and transdermal clonidine therapy. PMID- 11198613 TI - Plasmapheresis in a very young infant with atypical hemolytic uremic syndrome. AB - Atypical hemolytic uremic syndrome (HUS) is a heterogeneous group of disorders, the pathogenesis of which is unclear. Plasma transfusions and plasmapheresis are widely used modes of therapy for adults with this life-threatening syndrome. There is very limited experience in using plasmapheresis therapy in children and infants with atypical HUS. Plasmapheresis, which is considered a relatively safe procedure in adults and older children, may be hazardous in neonates and very young infants and can result in severe complications. We report a 2-month-old infant with idiopathic atypical HUS, who was successfully treated with a 1-month course of plasmapheresis during the acute phase of the disease. Appropriate preparations as well as several adjustments were made in order to meet the special needs of this very young infant who, to the best of our knowledge, is the youngest reported patient with atypical HUS to undergo plasmapheresis. Plasmapheresis therapy of the infant was not associated with any complications of the procedure and resulted in marked clinical improvement. We conclude that plasmapheresis in neonates and in very small infants is technically feasible, can be performed without major complications, and may be of benefit in individual cases. PMID- 11198614 TI - Macrohematuria with electron-dense deposits in a 14-year-old boy with minimal change nephrotic syndrome. PMID- 11198615 TI - Gastroesophageal reflux in hemolytic uremic syndrome. PMID- 11198616 TI - Antithrombin III, protein S, and coagulation in the nephrotic syndrome. PMID- 11198617 TI - Trisomy 21 with hypercalcemia, hypercalciuria, medullary calcinosis and renal failure--a syndrome? PMID- 11198618 TI - The renin angiotensin system in bypass graft surgery. AB - The renin angiotensin system is implicated in the development of vein graft disease after coronary artery bypass surgery. Components of this system have been shown to play important roles in determining the short-term and long-term performance of coronary artery bypass grafts. Significant differences exist in the commonly used arterial and venous grafts in angiotensin converting enzyme activity and angiotensin responses. The existence of a dual enzyme pathway in angiotensin II formation has also been demonstrated. Such findings have implications for the use of AT1-receptor antagonists over enzyme inhibitors to improve graft performance and prevent the development of coronary artery bypass graft disease. PMID- 11198619 TI - Developments in robotic cardiac surgery. AB - A new generation of surgical telemanipulation systems has helped to overcome the limitations of conventional endoscopic tools. These computer-enhanced instrumentation systems provide tremor filtering and motion scaling and allow dexterous manipulations in confined spaces through ports or trocars. Using these systems, total endoscopic coronary artery bypass grafting both on the arrested and on the beating heart has been performed successfully. Repair of mitral valves as well as atrial septal defects has also been performed remotely through 1 centimeter incisions. Despite some early procedural success, operating times are prolonged and a number of conversions have been reported. Currently, the use of telemanipulation systems is restricted to selected patients and limited to very few indications. Further refinements in telemanipulator technology as well as integration of image-based navigation systems may expand the use of computer enhanced instrumentation systems in the near future. PMID- 11198620 TI - Trials comparing coronary artery bypass grafting with percutaneous transluminal coronary angioplasty and primary stent implantation in patients with multivessel coronary artery disease. AB - With marked improvements in stent technology as adjunct to balloon angioplasty for multivessel coronary disease, several newer trials are currently in progress reviewing the optimal revascularization strategy. This review provides background from older studies and addresses the current progress and design of these newer trials. PMID- 11198621 TI - Lipid lowering and coronary bypass graft surgery. AB - This article reviews the rationale for lipid lowering in patients who have coronary heart disease, and specifically for post-bypass patients. It has been well demonstrated that after coronary artery bypass graft surgery, atherosclerosis continues to progress in the native circulation and develops at an accelerated rate in saphenous vein bypass grafts. During the last decade, numerous clinical trials based on angiographic or clinical outcomes have clearly shown the beneficial effect of lipid lowering in coronary heart disease. Three trials (CLAS, post-CABG, and CARE) have demonstrated delayed progression of atherosclerosis in SVGs and/or a reduction of cardiac deaths, nonfatal MI, and the need for revascularization after lowering LDL-cholesterol. The recommended target of LDL cholesterol level of more than 100 mg/dl can be safely reached with diet and monotherapy using one of the statin drugs (HMG-CoA reductase inhibitors). Despite this widely-circulated information, there appears to be inadequate public and professional awareness of the importance of properly managing hyperlipidemia after coronary artery bypass graft surgery. PMID- 11198622 TI - Severe morbidity after coronary artery surgery. AB - When operations become safer, attention inevitably shifts from mortality to morbidity. Unfortunately, morbidity is more difficult to measure than death, but it is arguably of greater interest to the patient and to those from public or private institutions that have the responsibility for balancing a health care budget. Studies that focus on morbidity are currently few, and specific risk models are being developed. It is already evident that risk factors associated with hospital death are qualitatively different from risk factors associated with prolonged hospital stay. The study of morbidity after coronary artery surgery is important to surgeons and physicians, to assess quality of care and the impact of new treatments and procedures. PMID- 11198623 TI - Roles of endothelial dysfunction in coronary artery disease. AB - Endothelial dysfunction is an early and persistent vascular abnormality in the evolution of atherothrombotic disease. Risk factors for atherosclerosis promote an inflammatory oxidative environment in the vasculature that induces pathologic changes in endothelial function, including the support of enhanced smooth muscle tone, thrombosis, and smooth muscle proliferation. This article provides an overview of the molecular basis of endothelial dysfunction and of its diagnosis and treatment. PMID- 11198624 TI - Emerging concepts in metabolic abnormalities associated with coronary artery disease. AB - To an increasing degree, cardiology and endocrinology are finding a broadening interface. There is little doubt that atherosclerosis is in many ways a metabolic disorder, just as it is becoming increasingly clear that diabetes is a vascular disease. Framing such notions is evidence of diabetes as a risk equivalent for coronary disease, and clinical cardiovascular trials demonstrate the impact of altering lipid metabolism. Although the focus has been on statins and LDL, data continues to emerge for other therapies for triglycerides and HDL. These issues are discussed, as are future directions for metabolic therapeutic interventions for vascular disease. PMID- 11198625 TI - Cardiac allograft vasculopathy. AB - Cardiac transplantation has emerged as a valuable therapy for various end-stage cardiac disorders. Cardiac allograft vasculopathy (CAV), an unusually accelerated and diffuse form of obliterative coronary arteriosclerosis, determines long-term function of the transplanted heart. Cardiac allograft vasculopathy is a complicated interplay between immunologic and nonimmunologic factors resulting in repetitive vascular injury and a localized sustained inflammatory response. Dyslipidemia, oxidant stress, immunosuppressive drugs, and viral infection appear to be important contributors to disease development. Endothelial dysfunction is an early feature of CAV and progresses over time after transplantation. Early identification of CAV is essential if long-term prognosis is to be improved. Annual coronary angiography is performed for diagnostic and surveillance purposes. Intravascular ultrasound is a more sensitive diagnostic tool for early disease stages and has revealed that progressive luminal narrowing in CAV is in part due to negative vascular remodeling. Because of the diffuse nature of CAV, percutaneous and surgical revascularization procedures have a limited role. Prevention of CAV progression is a primary therapeutic goal. PMID- 11198626 TI - Intravascular hemodynamic factors responsible for progression of coronary atherosclerosis and development of vulnerable plaque. AB - The initiation, localization, growth, composition, and rupture of intracoronary atheromatous plaque-factors that define the natural history of coronary artery disease-are all dependent on inhomogenieties and irregularities of intracoronary local blood flow and endothelial shear stress. Restenosis of mechanically recanalized coronary arteries may be related in part to similar abnormalities of disturbed local flood flow and shear stress. Low or reversed shear stress leads to plaque development and progression. High shear stress contributes significantly to plaque rupture. Regions of hemodynamic stasis caused by major luminal irregularities may lead to thrombosis and myocardial infarction without plaque rupture. This review outlines the mechanisms that link hemodynamic factors to plaque development and rupture and describes in some detail recently developed techniques that, for the first time, make it possible to determine these factors in vivo in patients during routine cardiac catheterization procedures. PMID- 11198627 TI - Medical treatment for acute coronary syndromes. AB - The medical treatment of acute coronary syndromes with thrombolytic, antithrombin, and antiplatelet agents is a major area of research and a vast topic for clinical review. This review summarizes important recent findings on the background of existing pathological and clinical knowledge to provide an understanding of the basis of current therapy and the new therapies that are likely to be introduced in the near future. Current controversies regarding the management of these conditions and the choice between medical, interventional, and combined strategies in different situations are also discussed. PMID- 11198629 TI - Bibliography. Current world literature. Coronary artery surgery. PMID- 11198628 TI - Revascularization interventions for ischemic heart disease. AB - Coronary artery bypass grafting and percutaneous transluminal coronary angioplasty are now well established methods of myocardial revascularization. The choice of a method of revascularization depends on several clinical and angiographic parameters. Patients who derive the greatest benefit from coronary artery bypass grafting are those with left main coronary artery disease or those with three-vessel disease with left ventricular impairment. Patients with single vessel disease achieve more symptomatic relief with coronary angioplasty than with medical therapy alone, but with no improvement in long-term mortality. In nondiabetic patients with multiple-vessel disease, angioplasty and bypass grafting likely yield similar results, and the choice of revascularization technique rests on weighing the more invasive nature of bypass grafting against the need for additional future revascularizations with angioplasty. Diabetic patients with multiple-vessel disease seem to achieve better outcomes with bypass grafting. Minimally invasive bypass surgery is an evolving technique. It is less invasive in nature but its applications are limited, and its advantages over traditional bypass grafting have not yet been shown. Stenting now plays a major role in percutaneous revascularization and is performed in more than two thirds of all interventional procedures. It improves both the short-term and the long term outcomes of coronary angioplasty. Other novel percutaneous techniques such as directional or rotational atherectomy, laser angioplasty, or thrombectomy devices have not shown convincing superiority over coronary angioplasty alone. Transmyocardial laser revascularization can be performed surgically or percutaneously and may be beneficial in patients with angina refractory to traditional revascularization procedures. PMID- 11198630 TI - Bibliography. Current world literature. Ischemic heart disease. PMID- 11198631 TI - 8th Conference on Radioimmunodetection and Radioimmunotherapy of Cancer. October 12-14, 2000. Princeton, New Jersey, USA. Abstracts. PMID- 11198632 TI - The development of atopic disease and asthma. Proceedings of a workshop. 10-13 February 1999, Fulda, Germany. PMID- 11198633 TI - Ourania Horaitis: linking Human Mutation and the HUGO-Mutation Database Initiative. PMID- 11198634 TI - Life-threatening severe malarial anaemia. AB - Despite our improved understanding of the pathophysiology of severe malaria, major changes in clinical management have not been forthcoming. However, in the case of life-threatening severe malarial anaemia, preliminary evidence suggests that changes in current clinical practice rather than the introduction of novel interventions may improve child survival. This review argues that further research into the clinical physiology of this syndrome is required and could provide compelling evidence for changes in practice particularly with regard to blood transfusion. We focus on the syndrome of severe, symptomatic malarial anaemia associated with a metabolic acidosis which has a high fatality rate. However, it should be remembered that a far greater number of children without signs of life-threatening disease nonetheless experience significant morbidity from severe anaemia. Many of these less-severely ill children may also require blood transfusion. However, the mode and rationale for transfusion in this less severely ill group is specifically not addressed. Indeed, the arguments presented should not be extrapolated to suggest a uniform approach to transfusion is warranted, the role of blood in the less-critically ill child with severe malaria anaemia being a further area that requires urgent research. PMID- 11198635 TI - Lymphatic filariasis: setting the scene for elimination. PMID- 11198636 TI - Lymphatic filariasis: economic aspects of the disease and programmes for its elimination. PMID- 11198637 TI - New insights into the natural history and pathology of bancroftian filariasis: implications for clinical management and filariasis control programmes. PMID- 11198638 TI - Wolbachia bacteria of filarial nematodes in the pathogenesis of disease and as a target for control. PMID- 11198639 TI - Lymphatic filariasis in Ghana: from research to control. PMID- 11198640 TI - The role of NGDOs in disease elimination programmes: the lessons from onchocerciasis control. PMID- 11198641 TI - Tuberculosis treatment failure and drug resistance--same strain or reinfection? AB - Tuberculosis patients may have Mycobacterium tuberculosis in their sputum at the end of treatment, and may show new drug resistance, due to either inadequate treatment of the original episode or reinfection with a new strain during therapy. In a cohort study of mineworkers with tuberculosis in South Africa, 57 of 438 patients had positive sputum cultures 6 months after recruitment in 1995. Of the 31 patients who initially had fully sensitive strains, 3 developed multidrug resistance (MDR) and 3 single-drug resistance (SDR). Of the 6 who started with SDR, 3 became MDR. HIV infection was not associated with drug resistance at enrollment or 6 months later. We compared pairs of DNA fingerprints from isolates of M. tuberculosis at recruitment and 6 months later in the 48 patients for whom we had both available. In 45, the pairs were identical. In 1 patient, although both isolates were fully sensitive, the later fingerprint had 1 less band (transposition). In 2 pairs, the fingerprint patterns were completely different: one seemed to be the result of laboratory error and the other was a true reinfection with an MDR strain. Despite a high risk of infection, with a moderate proportion of background drug-resistant strains (11% SDR, 6% MDR), reinfection is not a common cause of treatment failure or drug resistance at 6 months. PMID- 11198642 TI - London School of Hygiene and Tropical Medicine Meeting at Keppel Street, London, 12 April 2000. The Professor Gerald Webbe Memorial Lecture: global control of schistosomiasis. PMID- 11198643 TI - Investigation of risk factors for porcine Taenia solium cysticercosis: a multiple regression analysis of a cross-sectional study in the Yucatan Peninsula, Mexico. AB - A cross-sectional survey for seropositivity to cysticercosis of pigs in the Yucatan Peninsula, Mexico, was carried out in 1996 together with a standardized questionnaire on predetermined individual pig and household risk factors for porcine infection. Serum samples from 697 pigs were analysed by immunoblot for antibodies to Taenia solium cysticercosis and questionnaires from 227 households in 18 villages were collected. All the data were analysed using multivariate analytical techniques taking household clustering into account. The overall porcine seroprevalence in the area was found to be 29%. The most important risk factors for seropositivity in pigs were presence versus absence of a toilet (adjusted odds ratio [adj. OR] 2.37, P = 0.005), crowded households (adj. OR 1.75, P = 0.034) and both corralling (adj. OR 2.14, P = 0.017) and letting pigs loose (adj. OR 2.32, P = 0.035) versus tying them up. There was evidence of clustering at household level and that possible risk factors at municipal or village level may also interact with higher risk management practices such as allowing pigs to run loose. PMID- 11198644 TI - The potential of ivermectin to control the malaria vector Anopheles farauti. AB - We investigated mortality in Anopheles farauti mosquitoes, a major coastal malaria vector in the south-west Pacific, fed on a volunteer who had taken a 250 micrograms/kg dose of ivermectin. High mortality was recorded in mosquitoes feeding during the first week after treatment of the volunteer, for instance 100 80% failed to survive 3 days. A long-term residual effect of ivermectin in the blood was indicated by a small but significantly higher mortality in mosquitoes fed 6 weeks after ivermectin was taken. These effects were included in malaria transmission models that incorporated host choice and host-induced mortality parameters. For the zoophilic An. farauti, ivermectin treatment of animals resulted in a greater reduction in malaria than ivermectin treatment of humans alone, whereas for an anthropophilic vector, treatment of humans was more important. This suggests that ivermectin treatment of animals could have an important role in malaria control where An. farauti is the vector. Improvement in the health of humans and domestic animals through control of parasitic worms and mites might encourage community participation in strategies involving ivermectin. PMID- 11198645 TI - The use of live-bait traps for the study of sylvatic Rhodnius populations (Hemiptera: Reduviidae) in palm trees. PMID- 11198646 TI - Spraying houses in the Peruvian Andes with lambda-cyhalothrin protects residents against cutaneous leishmaniasis. AB - A household vector control trial was carried out in the Peruvian Andes to measure the effect of spraying inside walls and ceilings with lambda-cyhalothrin on the risk for residents of cutaneous leishmaniasis caused by Leishmania peruviana. The mortality rates of Lutzomyia verrucarum measured with WHO contact bioassay cones set on adobe walls characteristic of the endemic region indicated an LD95 for lambda-cyhalothrin of about 20 mg/m2, and no reduction in effectiveness for at least 6 months on indoor adobe walls sprayed with 25 mg/m2. A random selection of 112 houses were sprayed (starting in 1992/93) at 6-monthly intervals with a mean dose of 34 mg/m2, leaving 154 control houses (with closely matched pre intervention measurements of incidence and sandfly abundance). Comparisons of pre and post-intervention sandfly indoor abundance, measured at regular intervals for up to 2 years using CDC light traps, in 22 sprayed and 21 control houses demonstrated that spraying significantly reduced the indoor abundance of Lu. verrucarum by an average of 78% and of Lu. (Helcocyrtomyia) peruensis by 83%. Spraying was also associated with a significant reduction of 77% in the proportion of bloodfed sandflies collected in light traps. The proportion of susceptible householders acquiring leishmaniasis during the trial was significantly reduced by 54% as a result of spraying. The observed impact of spraying was greatest, 81% (95% confidence intervals 20-95%), when the cases detected during the first 6 months after the intervention were excluded from the analysis, suggesting a significant pre-patent period. PMID- 11198647 TI - Rural and urban differences in diabetes prevalence in Tanzania: the role of obesity, physical inactivity and urban living. AB - A population-based survey in 1996 and 1997 of 770 adults (aged > or = 15 years) from an urban district of Dares Salaam and 928 from a village in rural Kilimanjaro district (Tanzania) revealed that the prevalence of diabetes, impaired fasting glucose (IFG), overweight, obesity, and physical inactivity was higher in the urban area for men and women. The difference between urban and rural prevalence of diabetes was 3.8 [1x1-6.5]% for men and 2x9 [0x8-4.9]% for women. For IFG, the difference was 2x8 [0x3-5x3]% for men and 3x9 [1x4-6x4]% for women; for overweight and obesity, the difference was 21.5 [15.8-27.1]% and 6.2 [3x5-8.9]% for men and 17x4 [11.5-23.3]% and 12.7 [8x5-16x8]% for women, respectively. The difference in prevalence of physical inactivity was 12x5 [7.0 18.3]% for men and 37.6 [31x9-43.3]% for women. For men with diabetes, the odds for being overweight, obese and having a large waist:hip ratio were 14.1, 5.3 and 12.5, respectively; for women the corresponding values were 9x0, 10x5 and 2x4 (the last not significant) with an attributable fraction for overweight between 64% and 69%. We conclude that diabetes prevalence is higher in the urban Tanzanian community and that this can be explained by differences in the prevalence of overweight. The avoidance of obesity in the adult population is likely to prevent increases in diabetes incidence in this population. PMID- 11198648 TI - The epidemiology of febrile malaria episodes in an area of unstable and seasonal transmission. AB - This study investigated the epidemiology of uncomplicated falciparum malaria in an area of unstable and seasonal transmission in eastern Sudan. About 90% of malaria morbidity in this region occurs in the months of September to November, and very few malaria cases occur during the intensely arid Sudanese dry season and during years of drought. The malaria situation in the study site, the village of Daraweesh, was analysed during 3 consecutive malaria seasons in 1993-95 during which the 457 inhabitants suffered at total of 436 episodes of falciparum malaria. Using an Andersen-Gill proportional hazard model for recurrent events stratified by family, we have calculated the relative hazard for clinical malaria episodes by age, sex, haemoglobin genotype, blood type and infection in the previous season. The malaria risk was significantly lower in individuals aged 20 88 years than in the 5-19 years age-group. The relative protection due to adulthood varied between seasons (relative risk, RR, 0x34 to 0x67). Serological data were not consistent with the hypothesis that the age difference in incidence was due to differences in exposure. During the 1993 season the malaria incidence in males was lower than in females (RR = 0x75), during the 1994 season the incidences were comparable, whereas males had an increased risk of malaria in 1995 (RR = 1x87). The relative risk in individuals carrying the haemoglobin AS genotype compared to homozygous AA individuals was 0x57. PMID- 11198649 TI - Mosquito distribution and entomological inoculation rates in three malaria endemic areas in Gabon. AB - Mosquitoes were collected during 3 separate periods in 3 areas of different malaria transmission rates in the province of Moyen Ogooue, Gabon, within 1 year (July 1996-May 1997). The campus of the Albert Schweitzer Hospital (HAS) and 2 villages, Bellevue and Tchad, were investigated. A total of 19,836 specimens were collected: 13,122 Mansonia, 3944 Anopheles, 2755 Culex and 15 Aedes were captured. The number of mosquitoes was 7896 and 7995 in July to August and from April to May respectively, and dropped to approximately half in November to December. The individual species showed a different distribution pattern in the 3 study areas. In Tchad we found the lowest number of mosquitoes and also the fewest Anopheles, but when we investigated the number of Plasmodium falciparum infected Anopheles sp. we observed the highest entomological inoculation rate (EIR) there. The EIRs were 23 in HAS, 53 in Bellevue and 61 in Tchad. The method used to determine the number of infected mosquitoes was an enzyme-linked immunosorbent assay (ELISA), confirmed by a polymerase chain reaction-based approach. The ELISA alone revealed too many false-positive mosquitoes. PMID- 11198650 TI - Epidemic Schistosoma mansoni in a known S. haematobium area. AB - An epidemic of bloody diarrhoea was observed in 1997 and 1998 in Bessoum, north Cameroon. Of 1176 inhabitants, 16.7% went for medical consultation to a public health centre located 10 km away. This epidemic was probably due to the recent introduction of Schistosoma mansoni in an ancient focus of S. haematobium, following the development of irrigated farming. The prevalences amongst primary school children were 76.6% for S. haematobium in urine, and 60.9% for S. mansoni in stool. S. mansoni was found in urine in 28.1%. This epidemic emergence may be secondary to interspecific competition between the 2 schistosomes. PMID- 11198651 TI - Epidemiology of paragonimiasis in Colombia. AB - Five newly discovered endemic foci for paragonimiasis in Colombia are described for the first time. The disease was diagnosed in 24 people from the Embera Indian communities located at the Colombian Pacific Coast and investigated in 1993-98. We also describe the clinical, epidemiological and treatment response aspects. In these foci an Aroapyrgus sp. snail different from A. colombiensis was found to be the first intermediate host, and the crab Hypolobocera emberarum nsp. the second intermediate host. PMID- 11198652 TI - Meningitis seasonal pattern in Africa and detection of epidemics: a retrospective study in Niger, 1990-98. AB - Control of epidemic meningitis is still an unresolved problem in Africa. WHO has promoted the use of surveillance and response following alerts based on weekly threshold levels. In order to avoid any waste of resources related to false positive alerts, it was decided not to choose too sensitive thresholds. This policy, however, leads to delayed response. The seasonal pattern of epidemics provides a solution to this dilemma. We carried out a retrospective survey of district-level surveillance data in Niger from June 1990 to June 1998. We identified an early and late meningitis season. Following this pattern, we studied the performance of the WHO-recommended threshold as compared to alternative thresholds for identifying early, late and non-epidemic district years (DYs). (ADY was defined as a 52-week period starting in the last week of June, at the district level). We studied 296 DYs, comprising 50 early epidemic, 38 late epidemic, and 208 non-epidemic DYs. Early epidemics were more often large and accounted for almost 75% of total cases. When applied no later than the first week of March, a highly sensitive alternative threshold resulted in initiation of an alert, with a median of 3 weeks earlier than the standard threshold, with no false-positive alerts, i.e., a specificity of 1. PMID- 11198653 TI - Seroprevalence of human herpesvirus 6 in Andino Punenos (Argentina). AB - We carried out a seroepidemiological survey to define the prevalence of human herpesvirus 6 (HHV6) infection in an aboriginal population (Andino Punenos) from a remote region in north-west Argentina. Antibodies against HHV6 (total IgG and the 4 subclasses of IgG) were studied in 84 serum samples (collected in 1995 and stored at -70 degrees C), using core blood mononuclear cells infected with HHV6 in an immunofluorescence assay. Of the 84 samples, 70 (83%; 95% confidence interval, 75-91%) exhibited IgG antibodies against HHV6. No significant differences in the frequency of humoral immunity were found among the 4 age groups studied (mean ages 13, 31, 47 and 70 years) namely, 75%, 89.7%, 79.2% and 100%, respectively. HHV6-specific IgG1 was found in all the positive serum samples tested but none of them contained specific IgG2, IgG3 and IgG4. These results confirmed a high rate of infection with HHV6 within this aboriginal group in Argentina and an IgG1 anti-HHV6 activity compatible with a maintenance of immunity. PMID- 11198654 TI - Serum antigen detection in the diagnosis, treatment, and follow-up of neurocysticercosis patients. AB - The efficacy of albendazole (ABZ) treatment for human neurocysticercosis (NCC) was assessed by using a monoclonal antibody-based parasite antigen detection ELISA which specifically detects the products of living cysticerci in human serum. The assay displayed 85% diagnostic sensitivity, detecting 39 of 46 NCC cases. Only patients with a single viable cyst or only enhancing lesions (degenerating parasites) were seronegative. Specificity of the assay was 92% (23/25) when tested in healthy Peruvian volunteers. In 'cured' patients, in whom all parasites died after ABZ therapy, parasite antigen levels fell sharply by 3 months post treatment. This pattern was not observed in patients refractory to treatment. The sensitivity of the assay with serum samples, and its ability to identify successfully treated patients, make this monoclonal antibody-based ELISA the test of choice for the follow-up of NCC cases. PMID- 11198655 TI - Sputum concentration improves diagnosis of tuberculosis in a setting with a high prevalence of HIV. AB - Sputum microscopy for acid-fast bacilli (AFB), although relatively insensitive, is still the cornerstone of tuberculosis (TB) diagnosis in the developing world. Its diagnostic value has been eroded owing to the increasing number of HIV related smear-negative pulmonary TB cases. Concentration of sputum by centrifugation after liquefaction with sodium hypochlorite is a possible means of increasing the sensitivity of direct microscopy. This procedure has been studied recently in developing countries although with conflicting results. The aim of our study, performed in 1996 in Addis Ababa, Ethiopia, was to evaluate the sensitivity of the concentration method in a large cohort of consecutive patients with suspected pulmonary TB. We show that the overall sensitivity increased from 54.2% using conventional direct microscopy to 63.1% after concentration (P < 0x0015). In HIV-positive patients, sensitivity increased from 38.5% before to 50.0% after concentration (P < 0x0034). The significant increase in yield of AFB in HIV-positive patients suggests that this method has a place in routine diagnosis of pulmonary TB in countries with a high prevalence of HIV. PMID- 11198656 TI - Detection of 'Norwalk-like viruses' in Vellore, southern India. PMID- 11198657 TI - Presence of pro-oxidants in plasma of patients suffering from falciparum malaria. AB - Haemolysis is the major cause of anaemia in acute Plasmodium falciparum malaria, destroying both parasitized and non-parasitized erythrocytes. Oxidative stress on erythrocytes is considered an important mechanism of haemolysis. Since non parasitized erythrocytes are also destroyed, the extracellular environment of the erythrocyte may be a contributor to the oxidative stress. To examine the influence of extracellular factors on oxidative stress and haemolysis, baseline values of erythrocyte thio-barbituric acid-reactive substance (ETBAR) and haemolytic indices such as plasma haemoglobin and lactate dehydrogenase (LDH) were estimated in 19 children in Orissa (India) with acute P. falciparum malaria (haemoglobin level < or = 70 g/L). The indices were measured after incubating cross-matched isogroup adult control erythrocytes with patient's plasma, and patient's erythrocytes with adult control plasma both in presence of and in absence of t-butyl hydroperoxide (t-BHP). The procedure was repeated in the blood of 19 age- and sex-matched non-malarial children. Baseline plasma LDH, haemoglobin and ETBAR concentrations were significantly greater in malaria patients than non-malarial children (P < 0.001 for all). Post-incubation values of ETBAR and plasma haemoglobin were significantly higher (P < 0.05) when adult control erythrocytes were incubated with patient plasma, and plasma haemoglobin was significantly higher (P < 0.05) in incubates of patient erythrocytes with adult control plasma, than their respective pre-incubation values when incubated in absence of t-BHP. These differences were not noticed in the incubates of non malarial children with healthy adult control samples. When incubated in presence of t-BHP all the post-incubation values in the patients were significantly higher than their respective pre-incubation values and post-incubation values without t BHP (P < 0.001). In non-malarial control samples, only ETBAR concentration was higher than their respective pre-incubation and post-incubation values without t BHP (P < 0.01). All the values for post-incubation samples with t-BHP were significantly higher in patients than controls (P < 0.001). In post-incubation samples of control erythrocytes and patient plasma in presence of t-BHP, ETBAR correlated inversely with pre-incubation haptoglobin values (P < 0.001). Thus, plasma of acute malaria patients appears to contain pro-oxidants, which may contribute to extracellular oxidative stress on both parasitized and non parasitized erythrocytes. PMID- 11198658 TI - Randomized comparison of mefloquine-artesunate versus quinine in the treatment of multidrug-resistant falciparum malaria in pregnancy. AB - Since no effective malaria prevention measures have been identified for pregnant women living on the western border of Thailand, prompt diagnosis and efficient treatment are paramount, although drug resistance in Plasmodium falciparum has narrowed the treatment options. An open randomized comparison of supervised quinine (10 mg salt/kg every 8 h) for 7 days (Q7) versus mefloquine 25 mg base/kg (total dose) plus artesunate 4 mg/kg per day for 3 days (MAS3) was conducted in 1995-97 in 108 Karen women with acute uncomplicated falciparum malaria in the second or third trimesters of pregnancy. The MAS3 regimen was more effective than the Q7 regimen: day 63 cure rates were 98.2% (95% CI 94.7-100) (n = 65) for MAS3 and 67.0% (95% CI 43x3-90x8) (n = 41) for Q7, P = 0x001. The MAS3 regimen was also associated with less gametocyte carriage; the average person-gametocyte weeks for MAS3 was 2.3 (95% CI 0-11) and for Q7 was 46x9 (95% CI 26-78) per 1000 person-weeks, respectively (P < 0.001). MAS3 was significantly better tolerated. These evident advantages must be balanced against a possible increased risk of stillbirth with the use of mefloquine in pregnancy. Further randomized studies assessing the safety and efficacy of other artemisinin-containing combination regimens in pregnancy are needed urgently. PMID- 11198659 TI - The antimalarial activity of Vernonia amygdalina Del (Compositae). PMID- 11198660 TI - Miltefosine in a case of visceral leishmaniasis with HIV co-infection; and rising incidence of this disease in India. PMID- 11198661 TI - Safety and immunogenicity of a killed Leishmania (L.) amazonensis vaccine against cutaneous leishmaniasis in Colombia: a randomized controlled trial. AB - The safety and immunogenicity of an intramuscular (i.m.) and intradermal (ID) formulation of autoclaved Leishmania (Leishmania) amazonensis vaccine was evaluated in 296 volunteers in a randomized, placebo-controlled, double-blind trial in Colombia. There were 4 vaccination groups: i.m. vaccine, i.m. placebo, ID vaccine, and ID placebo. The ID formulations were mixed with BCG as adjuvant at the time of injection. For each group, 3 vaccinations were given with a 20-day interval between injections, and adverse events were monitored at 20 min, and at 2, 7 and 21 days after each injection. BCG-induced adverse reactions resulted in cancellation of the third vaccine administration in the ID groups. Antibody titres did not differ significantly between the groups. Montenegro skin-test conversion was achieved by 86.4% and 90% of the i.m. vaccine group and by 25% and 5% of the i.m. placebo group 80 days and 1 year after vaccination, respectively. A significant increase in mean Leishmania-antigen lymphocyte proliferation indexes was observed after i.m. vaccine immunization, but not after i.m. placebo immunization, 80 days and 1 year after vaccination. Significant levels of IFN gamma but not IL-10 were observed 1 year after vaccination in the i.m. vaccine group compared to the i.m. placebo group. The good safety profile and evidence of Th1 immune reactions due to i.m. vaccination in this phase-I/II study suggest that a population-based phase-III efficacy trial of the i.m. vaccine should be initiated. PMID- 11198662 TI - Chikungunya fever as a risk factor for endemic Burkitt's lymphoma in Malawi. AB - The geographical and age distributions of endemic Burkitt's lymphoma (eBL), in Africa, parallel those of certain arboviruses, which include chikungunya fever. Increased incidences of antibodies to assorted arboviruses, including chikungunya, have been found in eBL sera compared to controls. An increased incidence and space-time case-clusters of eBL occurred during a chikungunya fever epidemic which were confirmed by serology and clinical observation. The present study, conducted in 1987-89, involved 108 eBL patients, and 97 local and 111 hospital controls. We examined, as hospital controls, patients with afebrile, non malignant conditions admitted to Kamuzu Central Hospital, Malawi, during the eBL patients' first admission there. Analyses were for hospital controls and eBL patients at the end of their first admission and for local controls and eBL patients at the beginning of their third admission, about 8 weeks after the day of first admission, because of the local controls' temporal bias. Patients in case-clusters were among those seropositive for chikungunya virus, with a history compatible with arbovirus infection preceding the lymphoma, suggesting involvement of chikungunya virus in the case-clusters and a possible association between recent infection with this virus and development of the lymphoma. eBL patients were significantly more likely to be seropositive for chikungunya virus antibody (68x5%) than either hospital controls (46.8%) or local controls (50x5%) (P = 0x002 and 0x009, respectively), raising the possibility of an association between infection with an arbovirus and developing eBL in children already primed by holoendemic malaria and Epstein-Barr virus infection. PMID- 11198663 TI - Development of anti-filarial antibodies in a group of expatriate mine-site workers with varying exposure to the disease. PMID- 11198664 TI - Detection of ehrlichiae in African ticks by polymerase chain reaction. PMID- 11198665 TI - The parting glass. PMID- 11198666 TI - Congratulations from the editor of Journal of Occupational and Environmental Medicine. PMID- 11198667 TI - The recollections and musings of a former editor. PMID- 11198668 TI - The three faces of Occupational Medicine: printed paper, problems in practice, and professional purpose. AB - The 50-year run of the journal Occupational Medicine and its forbears demonstrates the ways in which UK occupational medical practice has developed and changed since 1950. This has been in response to changes in society, technology and medicine. The journal has played an important part in education and professional development. It has also been the voice for the aspirations and concerns of its readers. Two aspects stand out: the development of occupational medicine as a specialty, and the way in which a medical model for occupational health service provision has been championed. A distinguished line of journal editors has been central to the crystallization of ideas within occupational medicine and their editorials map out professional successes and challenges over the years. PMID- 11198669 TI - Age and ageing: an overview. AB - Europe is ageing, as exemplified by the UK population where, in the foreseeable future, more people will be over than under age 50: industry appears slow to recognise and appreciate all that older workers still have to offer: bundling them off into early retirement wastes precious talents. Memory difficulty is not an inevitable part of ageing. PMID- 11198670 TI - Designing and managing healthy work for older workers. AB - Throughout many countries in the developed world, largely because of increasing life expectancy, the population is ageing. One of the economic implications of this demographic change is that workers may need to work longer and retire later than they have done in recent years. Much needs to be done to ensure that work remains a positive experience for workers throughout their career trajectories, and that it does not damage their health. The major contemporary challenges to health at work are those associated with the way work and work organizations are designed and managed. This is especially true for older workers. This paper focuses on the relationships between age and work performance, between age and work-related health, and between age and work-related stress. It concludes that there remains considerable scope for designing optimal work systems to harness the potential and protect the health of older workers. This important initiative will require a co-ordinated and multidisciplinary occupational health strategy. PMID- 11198671 TI - Acquisition and application of new technology skills: the influence of age. AB - This paper reviews the literature relating to the effects of ageing on the acquisition and application of new technology skills. Experiential, physiological, and cognitive factors are identified that place older adults at a disadvantage, relative to younger adults, when using new technologies. Consistent with this position, experimental evidence indicates an advantage for younger adults in speed of task performance, coupled with a tendency toward greater accuracy. The possibility that these differences can be overcome by means of training intervention is considered. However, it seems that age differences in performance persist, regardless of a training regime. Although some older adults are capable of high levels of performance, these tend to be individuals of high cognitive ability, relative to their peers. When age group means are considered, the only way that older adults are able to equal the performance of younger adults on new technology tasks is through additional practice. PMID- 11198672 TI - Ageing and fitness to work. AB - Ageing workers can be found in almost all occupations. Assessment of fitness to work in these workers is important, as it aims to match their functional capacity (which is reduced compared to younger workers), to the demands of their work (which may remain the same as that for younger workers). This outcome of assessment is influenced by the interaction between functional capacity, state of health, the nature of work, and possibilities for work accommodation. The assessment of functional capacity should include physical, mental and social capacity, as well as assessment of any disability. In addition to clinical or laboratory measurements, several authors have suggested the use of a 'work ability index' for specific occupations as a practical means of selecting the appropriate worker for the job. This index can also be used for monitoring functional capacity. In addition, as for any fitness to work assessment, a good understanding of the nature of the work and the work environment is required, and possibilities for work accommodations considered. While changes in the work environment and working conditions can be made to suit the functional capacity of the ageing worker, the maintenance of functional capacity is another important issue. There is a place for a greater role for disease screening and health promotion for such workers. PMID- 11198673 TI - What are the causes, prevention and treatment of hearing loss in the ageing worker? AB - Hearing loss is more common in the ageing population as compared to young adults. Individuals are not protected from other causes of hearing loss just because they are in work. Their hearing may therefore be at risk from causes not related to their occupation. Some factors may be synergistically linked to noise exposure, thus increasing the effect of noise on hearing. Although some traumatic and infective causes of hearing loss are amenable to treatment, most occupational hearing loss is not curable once present and rehabilitative measures are the only option. General health and safety measures must be maintained throughout a worker's employment whatever their age. PMID- 11198674 TI - Surveillance of work-related diseases by occupational physicians in the UK: OPRA 1996-1999. AB - The Occupational Physicians' Reporting Activity (OPRA) surveillance scheme for occupational physicians has now been in place for 4 years. During this period, an estimated 43,764 new cases of work-related disease have been reported. Musculoskeletal conditions make up nearly half (49%) of all cases; mental ill health and skin disease account for 20% each, with respiratory conditions (8%) and hearing loss (5%) seen in lower proportions. Overall, eight of 42 diagnoses made up four-fifths of the new cases reported by occupational physicians. These were hand and arm disorders (8052 estimated cases), contact dermatitis (7104), disorders of the lumbar spine (6000), anxiety and depression (4788), work-related stress (3336), hearing loss (2100), elbow disorders (2040), and asthma (1680). Dermatitis and hearing loss were most frequent in manufacturing industries, lower back complaints in health care, and upper limb disorders in automotive manufacture. Psychiatric illnesses presented a different pattern, mainly affecting those in health, education and social service. PMID- 11198675 TI - Non-attendance for Social Security medical examination: patients who cannot afford to get better? AB - This paper reports results from a cross-sectional study of 290 consecutive Invalidity Benefit cases in the north-west of England referred to the Benefits Agency Medical Service in 1994. The hypothesis is that socio-economic factors, such as high locality unemployment rates, may be implicated, not only in the initial causation of ill health, but also in its continuance, by giving incentive to the ongoing adoption of the sick role. Results showed that residence in Liverpool, a diagnosis of anxiety/depression or simple back pain, and age under 40 years were all significantly related to non-attendance (P < 0.01). Claimants from Liverpool were also younger, overall, more likely to be called for examination, but less likely to be found fit for work if they attended. This suggests that some claimants may not attend examination because they fear being found fit for work and losing the benefit on which they and their families depend. PMID- 11198676 TI - Cytochrome P450-2E1 and glutathione S-transferase mu polymorphisms among Caucasians and mulattoes from Brazil. AB - The variable interindividual ability to metabolize environmental toxicants, also known as metabolic polymorphism, may be of substantial importance in the modulation of cancer risk. The ethnic distribution of these polymorphisms could be interesting in order to establish an association with cancer risk or even to establish selective advantage of some genotypes. Cytochrome P450 2E1 (CYP2E1) is a secondary enzyme that can metabolize ethanol, and glutathione S-transferase (GSTM1) is thought to be involved in the detoxification of epoxides and polycyclic aromatic hydrocarbons. Mutation in these genes was investigated in a random sample of healthy subjects from Sao Paulo, Brazil, which included 206 Caucasians and 86 mulattoes. Pst I restriction fragment length polymorphism (RFLP) in the 5'-flanking region of the CYP2E1 gene has been identified in 10.2% of Caucasian individuals and in 11.6% of mulattoes. For GSTM1 the frequency of the null genotype was significantly higher in Caucasian individuals (60.2%) than in mulattoes (41.9%). Allele frequencies were (1) CYP2E1 locus: P = 0.949, q = 0.051, se(p) = se(q) = 0.011 among Caucasians; and p = 0.942; q = 0.058; se(P) = se'(q) = 0.018 among mulattoes; and (2) GSTM1 locus: p = 0.224, q = 0.776, se(p) = se(q) = 0.022 among Caucasians; and p = 0.353; q = 0.647; se(p) = se(q) = 0.041 among mulattoes. PMID- 11198677 TI - Burnout syndrome: a disease of modern societies? AB - In the light of social change and a transformation in the work situation, interest in the problem of burnout has grown over the past decade. There is a conspicuous discrepancy, however, between what is regarded as certain knowledge and what is published opinion. To date, there is no generally accepted definition of burnout, or binding diagnostic criteria. According to the most common description at present, burnout syndrome is characterized by exhaustion, depersonalization and reduced satisfaction in performance. Because of its aetiopathogenesis, burnout is today mainly regarded as the result of chronic stress which has not been successfully dealt with. This paper gives an overview of the current definition for burnout syndrome and states possible contemporary hypotheses for its aetiology. By examining diagnostic criteria and possible therapies, methods of prevention are discussed. There is an urgent need for further investigations to determine whether burnout syndrome is a work-related disease. PMID- 11198678 TI - An investigation of the relationship between psychological health and workload among managers. AB - BACKGROUND: Anecdotally, many workers complain of stress at work. However, the relationship between work and stress needs clarification to allow risk assessment and risk management of this hazard in the workplace. OBJECTIVES: To examine relationships between working hours, perceived work stressors, and psychological health in a group of managers. METHODS: Managers at two factories were invited to participate in an anonymous cross-sectional survey. All were asked to complete a work diary for a period of 1 week and a questionnaire comprising the 30-item General Health Questionnaire, an anxiety and depression scale, and questions identifying perceived workplace stressors. RESULTS: Over 60% of managers were above the threshold of caseness on at least one measure of psychological health. No statistically significant relationship was demonstrated between actual hours of work and psychological health. A relationship was demonstrated between some perceived workplace stressors and actual hours worked, and between some perceived workplace stressors and psychological health. CONCLUSIONS: A large proportion of managers in a typical production environment appeared at risk of developing psychological illness. Hours of work were not directly related to psychological health, but were significantly associated with individual perception of some work stressors which, in turn, were associated with measures of psychological health. Perceived workload appeared more important in determining psychological health than actual workload. PMID- 11198679 TI - Occupational health in the USA in the 21st century. AB - Comparable to the confusion encountered in the birth of the machine age is the perplexing reconfiguration of the United States' health care system. Paralleling the advances in medicine have been the divesting mergers and downsizing of industry, coupled with globalization, which have released millions of long-time workers. The labour contingent is changing, with the addition of great numbers of women and immigrant workers, and the manufacturing economy has become one of service and information. Serving the occupational health (OH) needs of such a force have been the professional societies of physicians, nurses, and industrial hygienists, with their members providing care in a broad variety of facilities. It is possible that a national organization, including all these disciplines, would have a greater voice in the protection of workers' health. Immediate leadership of an occupational health service (OHS) can be rotated among the disciplines, so that competition for primacy among the professionals would end. The new workforce demands culture sensitivity among OH personnel and polylingual capabilities may be demanded in the future. Management skills will be required of all in OH, and greater participation of employees in OH policy will characterize the decades ahead. Nearly neglected up to now, occupational mental health programming will be required to meet the real needs of workers, and to counter the move to outsource OH services, where little patient contact results. Behavioural safety, total quality management, and application of the rapidly developing technologies in health care will define the 21st century efforts in OH. Remaining issues, such as violence, telecommuting injuries, the inclusion of alternative medicine, and women's health, among others, will see carry-over for resolution into the year 2000. PMID- 11198680 TI - Do symptomatic radiographers provide evidence for 'darkroom disease'? Nallon et al. Occup Med 2000; 50: 1:39-42. PMID- 11198681 TI - Do symptomatic radiographers provide evidence for 'darkroom disease'? Nallon et al. Occup Med 2000; 50: 39-42. PMID- 11198682 TI - Does vacation enable recuperation? Changes in well-being associated with time away from work. Strauss-Blasche et al. Occup Med 2000; 50: 167-172. PMID- 11198683 TI - It's official: evaluative research must become part of routine care in the NHS. PMID- 11198684 TI - Expedition health and safety: a risk assessment. AB - Little has been published on the risks of participating in an expedition. A questionnaire survey was conducted to quantify those risks and to determine how expedition organizers plan for medical mishaps. 246 expeditions, taking 2381 participants to more than one hundred countries, were studied retrospectively. 65 expeditions (26%) reported no medical incidents; the remaining 181 reported 835 in 130,000 man-days (6.4 per 1000 man-days). 59% of the medical incidents seen on expeditions were preventable, one-third of these being due to gastrointestinal upsets. 78% of medical incidents were classified as minor and only 5% (40) as serious. There was no excess of serious incidents in any particular organizational group or environment. The findings of this survey suggest that the health risks of participating in a well-planned expedition are similar to those encountered during normal active life. PMID- 11198685 TI - General practitioners' attitudes to sexual activity in under-sixteens. AB - In the UK, under-sixteen-year-olds with some exceptions can be provided with contraceptive care even if unwilling to inform their parents. Nonetheless, many teenagers express doubts about confidentiality in these circumstances, as well as fear of being judged. The attitudes of general practitioners in North and East Devon towards the Gillick ruling regarding the treatment of under sixteens for sexual health matters were assessed. They were asked to indicate their level of agreement or disagreement with a series of statements. 235 (73%) responded, and only 15 (6.5%) rejected the notion that the same duty of confidentiality applies to under-sixteens as to older patients. 76% did, however, prefer parents to know they had been consulted about contraception. Only 7 GPs believed that provision of contraception encourages under-age sex. Despite GPs' general acknowledgment of the importance of confidentiality in relation to sexual activity, teenagers may well be discouraged from seeking advice if they expect strong pressure to tell their parents. PMID- 11198686 TI - Knowledge and the Internet. PMID- 11198687 TI - Medical constraints on the quantum mind. PMID- 11198688 TI - Colorectal liver metastases: alternatives to resection. PMID- 11198689 TI - Public health outputs from the British Paediatric Surveillance Unit and similar clinician-based systems. PMID- 11198690 TI - Primary angiitis of the central nervous system. PMID- 11198691 TI - Evolving electrocardiographic changes in a patient with hyperthyroidism. PMID- 11198692 TI - Hermansky-Pudlak syndrome presenting with subdural haematoma and retinal haemorrhages in infancy. PMID- 11198693 TI - Sucking noise and collapse after central venous catheter removal. PMID- 11198694 TI - Femoral vein obstruction with an arthritic hip. PMID- 11198695 TI - Reversible dementia in Paget's disease. PMID- 11198696 TI - Two historical cases of giant epidermoid cyst of the skull, treated surgically. PMID- 11198697 TI - Clinical judgment. PMID- 11198698 TI - Surgical treatment for hidradenitis suppurativa. PMID- 11198699 TI - Innovation in the pharmaceutical industry. PMID- 11198700 TI - Educating health professionals about disability. PMID- 11198701 TI - A puzzle: where was the airgun pellet? PMID- 11198702 TI - Use of autologous limbal epithelial cells cultured on amniotic membranes for unilateral stem cell deficiency. PMID- 11198703 TI - A comparison of correlates of DSM-IV alcohol abuse or dependence among more than 400 sons of alcoholics and controls. AB - BACKGROUND: Alcohol dependence and abuse are defined as separate disorders. However, relatively few data are available about whether the same characteristics predict both syndromes. METHODS: Complete data were available from the 15 year follow-up of 411 men who originally had been evaluated from a university population at about age 20. Both baseline data gathered prospectively and the retrospective ratings in six domains of life functioning were analyzed for their relationship to the development of alcohol abuse or dependence during the follow up. RESULTS: Baseline characteristics of a family history of substance use disorders, the quantity and frequency of drinking, the history of alcohol-related problems, and the level of response to alcohol all predicted future alcohol abuse or dependence, but only an alcoholic second-degree relative or a first-degree drug-dependent family member differentially predicted dependence. Logistic regression analyses revealed that similar baseline characteristics combined to predict dependence and, separately, abuse. When the domains of functioning during the 15 years were included, positive alcohol expectancies, poor coping mechanisms, low level of social support, and drinking in the environment contributed to both dependence and abuse, although the relationship was stronger for dependence. CONCLUSIONS: The predictors and correlates of alcohol abuse and dependence in this group of men were similar. Further research in additional populations and on other drugs is needed to determine if the two syndromes overlap sufficiently to be combined. PMID- 11198704 TI - Effect of repeated exposure to alcohol on the response of the hypothalamic pituitary-adrenal axis of the rat: II. Role of the length and regimen of alcohol treatment. AB - BACKGROUND: Prior exposure to alcohol alters the adrenocorticotropin hormone (ACTH) response to a second drug challenge administered several days later. We used three models of alcohol treatment to investigate the mechanisms that may be involved in this phenomenon. METHODS: Adult male rats were exposed to alcohol vapors daily for 3 days (4-4.5 hr/day) and then were exposed to shocks or an intragastric injection of alcohol 7 days later (group A); were injected daily with alcohol (4.5 g/kg intragastrically) for 3 days and then exposed to shocks or an intragastric injection of alcohol 7 days later (group B); or were exposed to alcohol vapors for 6 days and exposed to shocks or an intragastric injection 24 hr later (group C). Control animals were not exposed to the vapors or received the appropriate vehicle. RESULTS: Compared with animals administered the vehicle, rats of groups A and B that had been exposed to alcohol all exhibited a significantly decreased ACTH response to a second drug challenge. In contrast, their ACTH response to footshocks was statistically comparable to that of vehicle pretreated animals. Rats of group C that had been exposed to alcohol for 6 days also showed decreased ACTH release when injected with alcohol 7 days later while responding normally to shocks. Measurement of anterior pituitary pro opiomelanocortin indicated that alcohol pretreatment had produced a 54% increase of these transcripts in group C and a 27% decrease in group A. There were no changes in pituitary receptors type 1 for corticotropin-releasing factor (CRFR1) in any of the groups. CONCLUSION: Regardless of whether they are delivered shortly before an acute alcohol injection or several days earlier, alcohol vapors or injections interfere with the ACTH response to the drug but not to shocks. Our results also suggest that changes in ACTH responses may not be correlated directly with small changes in pituitary pro-opiomelanocortin or CRFR1 mRNA levels. PMID- 11198705 TI - Thiamin treatment and working memory function of alcohol-dependent people: preliminary findings. AB - BACKGROUND: Wernicke-Korsakoff syndrome (WKS) is most often seen in people who are alcohol dependent. Treatment with thiamin may rapidly resolve acute symptoms. However, much evidence suggests that identification of WKS on clinical examination is relatively insensitive when compared with diagnosis at postmortem. No study has investigated the therapeutic effect of thiamin in a sample of alcohol-dependent people without the clinical triad of acute WKS. METHODS: We conducted a randomized, double-blind, multidose study of thiamin treatment in 107 subjects who were detoxifying from alcohol. Five groups of subjects were assessed with the Mini-Mental State Examination and were examined for the presence of neurological signs. Subjects were given different doses of intramuscular thiamin for two consecutive days. The posttreatment performance of these groups then was examined on a test of working memory derived from comparative neuropsychology, namely, the delayed alternation task. This test has been established as sensitive to the neuropathology of WKS. RESULTS: Pretreatment measures of mental status and neurological signs were equivalent across groups. Groups were equated with respect to the background variables of age, education, typical daily alcohol consumption, and years of drinking. On the posttreatment measure, a superior performance was found in the group that received the highest dose of thiamin, compared with the other four treatment groups. CONCLUSIONS: A therapeutic relationship between dose and working memory performance was indicated. These results have important implications for the management and prevention of WKS, but further investigations are needed to substantiate the nature of the therapeutic relationship. PMID- 11198706 TI - Alcohol and behavioral control: cognitive and neural mechanisms. AB - This article represents the proceedings of a symposium at the 2000 RSA Meeting in Denver, Colorado. The organizer/chair was Muriel Vogel-Sprott. The presentations were (1) Alcohol-induced impairment of inhibitory control: Some commonalities with attention deficit hyperactivity disorder, by Mark Fillmore; (2) Neural interactions that underlie response inhibition under alcohol: A functional magnetic resonance imaging investigation, by Craig Easdon; (3) Intentional control of behavior under alcohol, by Muriel Vogel-Sprott; and (4) Working memory and the disinhibiting effects of alcohol on passive avoidance learning, by Alicia Justius and Peter Finn. PMID- 11198707 TI - Differences in services utilization between white and Mexican American DUI arrestees. AB - BACKGROUND: Hispanics traditionally have been considered an underserved population in relation to medical care and related services utilization. METHODS: Selected health and social services utilization (both alcohol-specific and non alcohol-specific) during the last year was compared between a sample of 249 Mexican American (half of whom were born in Mexico) and 250 white participants interviewed in all five DUI (driving under the influence) treatment programs in one northern California county. RESULTS: Among those who met DSM-IV criteria for alcohol dependence and/or alcohol abuse, 49% of the white subjects compared with 59% of the Mexican American subjects reported no utilization, 77% of whites and 82% of Mexican Americans reported no utilization in which drinking was a factor, and 70% of whites and 80% of Mexican Americans reported no contact with an alcohol program. Mexican Americans were also significantly less likely to report contact with more than one program, and among Mexican Americans, those born in Mexico were significantly less likely to report utilization than those born in the U.S. CONCLUSIONS: The data suggest that despite the higher rates of heavy drinking found among Mexican American DUI arrestees (especially those born in Mexico) in this sample, Mexican Americans with an alcohol use disorder are less likely to use health and social services than whites, and this may be related to country of birth and related variables that include health insurance. SIGNIFICANCE: The data suggest that DUI programs may offer one of the few opportunities Mexican American problem drinkers have of establishing contact with the health and social service system and, as such, would be well positioned to also offer other types of alcohol-related health and social services and referrals to this underserved population. These findings have implications for intervention efforts for problem drinking and prevention of DUI among Mexican Americans, which are a rapidly growing ethnic minority in California. PMID- 11198708 TI - Improving alcoholism treatment across the spectrum of services. AB - This article represents the proceedings of a symposium at the 2000 RSA Meeting in Denver, Colorado. The chair was Michael E. Hilton. The presentations were (1) The effects of brief advice and motivational enhancement on alcohol use and related variables in primary care, by Stephen A. Maisto, Joseph Conigliaro, Melissa McNiel, Kevin Kraemer, Mary E. Kelley, and Rosemarie Conigliaro; (2) Enhanced linkage of alcohol dependent persons to primary medical care: A randomized controlled trial of a multidisciplinary health evaluation in a detoxification unit, by Jeffrey H. Samet, Mary Jo Larson, Jacqueline Savetsky, Michael Winter, Lisa M. Sullivan, and Richard Saitz; (3) Cost-effectiveness of day hospital versus traditional alcohol and drug outpatient treatment in a health maintenance organization: Randomized and self-selected samples, by Constance Weisner, Jennifer Mertens, Sujaya Parthasarathy, Charles Moore, Enid Hunkeler, Teh-Wei Hu, and Joe Selby; and (4) Case monitoring for alcoholics: One year clinical and health cost effects, by Robert L. Stout, William Zywiak, Amy Rubin, William Zwick, Mary Jo Larson, and Don Shepard. PMID- 11198709 TI - Genetic and environmental influences on alcohol metabolism in humans. AB - This manuscript represents the proceedings of a symposium at the 2000 RSA Meeting in Denver, Colorado. The organizer/chair was Ting-Kai Li. The presentations were: (1) Introduction to the Symposium, by Ting-Kai Li; (2) ALDH2 polymorphism and alcohol metabolism, by Shih-Jiun Yin; (3) ALDH2 promoter polymorphism and alcohol metabolism, by David W. Crabb; (4) Use of BrAC clamping to estimate alcohol elimination rates: Application to studies of the influence of genetic and environmental determinants, by Sean O'Connor; and (5) Effect of food and food composition on alcohol elimination rates as determined by clamping, by Vijay A. Ramchandani. PMID- 11198710 TI - Nursing experiences with an alcohol-intoxicated rat dam counteract appetitive conditioned responses toward alcohol. AB - BACKGROUND: Infant rats detect small amounts of alcohol (175 mg%) that are present in maternal milk whenever the dam is moderately intoxicated with alcohol. Interaction with an alcohol-intoxicated mother during the first 2 weeks of life facilitates the preweanling's subsequent discrimination of alcohol's orosensory attributes and produces conditioned aversion to alcohol. The present study further analyzed the hedonic content of infantile alcohol memories established in the nursing context by testing the interaction between experiences with an alcohol-intoxicated dam and learning procedures aimed at establishing an appetitive conditioned response toward alcohol. METHODS: Experiment 1 was to determine appropriate parameters to establish a reliable conditioned preference for alcohol in 16-day-old infants. For conditioning, intraorally infused sucrose solution (appetitive reinforcer) was paired with alcohol's orosensory cues derived from an acute state of alcohol intoxication (3 g/kg). Two control groups included an unpaired condition and a group given sucrose after water intubation. Infants then were evaluated in an alcohol intake test. Relative to control animals, a reliable conditioned preference for alcohol was registered in paired pups. In experiment 2, these conditioning procedures were applied to infant rats which, before conditioning, suckled from dams subjected to a 2.5 g/kg alcohol dose (intragastric) or from water-treated females during postpartum days 3, 5, 7, 9, 11, and 13. RESULTS: Experiment 2 showed that maternal treatment significantly affected the establishment of conditioned preferences for alcohol. Whereas pups reared by control dams exhibited reliable appetitive conditioning to alcohol, infants raised by alcohol dams completely failed to develop appetitive conditioning. CONCLUSIONS: The present results suggest that alcohol-related memories generated via infantile interactions with an intoxicated dam counteract subsequent conditioning of alcohol ingestion. In conjunction with prior studies, it is concluded that alcohol-related nursing experiences are capable of promoting alcohol memories with a negative hedonic content. PMID- 11198711 TI - Suppression of ethanol responding by centrally administered CTOP and naltrindole in AA and Wistar rats. AB - BACKGROUND: Both mu- and delta-opioid receptors have been implicated in the reinforcing actions of ethanol. However, selective opioid receptor antagonists have not altered ethanol intake in all rodent strains consistently, which suggests that genotype may modulate their suppressive effects. Therefore, we tested the effects of the selective mu-antagonist D-Pen-Cys-Tyr-D-Trp-Orn-Thr-Pen Thr-NH2 (CTOP) and the selective delta-antagonist naltrindole in both high drinking AA (Alko, Alcohol) and heterogeneous Wistar rats. METHODS: AA and Wistar rats were trained to respond for ethanol (10% w/v) in a two-lever operant condition by using a saccharin fading procedure. After stable baseline responding was established, rats were implanted stereotaxically either with a guide cannula above the lateral ventricle or with bilateral cannulas above the nucleus accumbens, basolateral amygdala, or ventral tegmental area. After postoperative recovery, AA and Wistar animals were tested after intracerebroventricular microinjections of either CTOP (0-3 microg) or naltrindole (0-30 microg) or subcutaneous injections of naloxone (0-1 g/kg), which was used as a reference antagonist. Effects of intracerebral microinjections of CTOP and naltrindole (both 0-500 ng) were tested only in Wistar rats. RESULTS: Subcutaneous naloxone and intracerebroventricular CTOP and naltrindole suppressed ethanol self administration in a similar manner in AA and Wistar rats. Cumulative response patterns indicated that naloxone and naltrindole had no effect on the initiation of responding but suppressed it later during the session, whereas CTOP also affected initiation. In Wistar rats, naltrindole microinjections into both the nucleus accumbens and basolateral amygdala decreased ethanol responding, whereas CTOP was effective only in the amygdala. Injections of these antagonists into the ventral tegmental area had little effect on ethanol intake. CONCLUSIONS: The results confirm previous results which showed that both mu- and delta-opioid receptors are involved in the regulation of ethanol self-administration and indicate that genetic differences between AA and Wistar rats produced by selection do not modify the effects of opioid antagonists. The nucleus accumbens and the basolateral amygdala may be important central sites for the mediation of their suppressive effects. PMID- 11198712 TI - Possible reasons why heavy drinking increases carbohydrate-deficient transferrin. AB - BACKGROUND: Transferrin is a globular protein synthesized in the liver that is responsible for iron transport in plasma. The structure of the molecule consists of two carbohydrate residues to which six sialic acid moieties can be attached. After periods of chronic, heavy alcohol consumption, carbohydrate-deficient transferrin (CDT) isoforms often increase, which makes CDT a useful marker in screening for alcohol abuse and monitoring progress of alcoholics in treatment. However, the precise mechanism behind CDT increase remains unknown. METHODS: A review of the most relevant literature on CDT was conducted with a computer assisted literature search. RESULTS: During the past several years, a number of studies have explored possible mechanisms that may account for the alcohol induced increase of CDT. An inhibition of protein synthesis and a general effect of alcohol on protein glycosylation have been reported. Although the exact mechanisms that underlie production of CDT are not yet fully understood, possible bases for the phenomenon are presented in this article. CONCLUSIONS: Experimental findings indicate that the ethanol-induced effect on glycoprotein metabolism is a multistep process in which protein transport and changes of enzyme activity may play an important role. PMID- 11198713 TI - Adverse drinking consequences among alcohol abusing intravenous drug users. AB - BACKGROUND: Heavy alcohol use is common among out-of-treatment injection drug users (IDUs); however, the relationship between alcohol and drug use behaviors in codependent populations is not well understood. Our specific objectives were (1) to describe the psychometric properties of the Drinker Inventory of Consequences (DrInC) in a sample of active IDUs, and (2) to compare DrInC scores of active IDUs with those reported for the alcohol treatment seeking sample on which the instrument was developed. METHODS: Interview data were collected from 187 active IDUs who scored positively (> or = 8) on the Alcohol Use Disorders Identification Test, who were recruited from a Providence, RI, needle exchange program (1998 1999). DrInC total and subscale scores for the 159 (85%) participants who met DSM IV criteria for alcohol abuse/dependence were analyzed. Six-month follow-up data were used to estimate test-retest reliability. RESULTS: The DrInC total scale exhibited high internal consistency and test-retest reliability. With the exception of adverse physical consequences, reliability estimates for DrInC subscales were good to very good. These data indicate higher subscale redundancy than reported for the development sample. Active IDUs had significantly higher adverse impulse control consequences than the alcohol treatment seeking population on which the instrument was developed. CONCLUSIONS: The DrInC exhibits desirable psychometric properties for assessing adverse drinking consequences in active IDU populations. IDUs who met DSM-IV criteria for alcohol abuse/dependence reported overall levels of adverse drinking consequences comparable with non-IDU alcohol treatment populations but were more likely to exhibit adverse impulse control consequences. PMID- 11198714 TI - Detection of alcohol abuse in neurological patients: variables of clinical relevance to the accuracy of the %CDT-TIA and CDTect methods. AB - OBJECTIVES: Alcohol-related neurological diseases are encountered frequently. Early diagnosis is essential, because minimal intervention effectively reduces hazardous alcohol consumption and may prevent permanent neurological damage. Carbohydrate-deficient transferrin (CDT) is a valuable tool for the identification of alcohol abuse, but for unselected patient populations, reduced test accuracy has been reported. Recently, factors other than alcohol use have been shown to influence CDT levels. Our aim was to identify clinically relevant factors that might reduce test accuracy. MATERIAL AND METHODS: We included 397 neurological patients consecutively hospitalized for seizures, ischemic stroke, or sciatica and 87 patients who attended routine outpatient controls for epilepsy. Blood samples were analyzed for CDT by using two commercially available tests, %CDT-TIA and CDTect. All patients underwent a semistructured clinical interview that included a record of the reported ethanol consumption during the last 8 days, and all completed the Alcohol Use Disorders Identification Test (AUDIT). Current medication, medical history, and demographic information also were obtained. RESULTS: Both tests were elevated in female antiepileptic drug users, compared with others who reported no recent ethanol intake. A higher number of false-positive cases was seen for CDTect than for %CDT. Various combinations of CDT and gamma-glutamyltransferase improved sensitivity, but at the cost of reduced specificity. Variables that predicted the variation of CDT included antiepileptic drug use, sex, body mass index, and smoking. Total transferrin levels were reduced significantly in postmenopausal women, whereas a falling trend was seen for CDTect. Transferrin alterations caused a higher number of false-positive results for CDTect than for %CDT. The area under the receiver operating characteristics curve for women was higher for CDTect than for %CDT, and for %CDT, the area under the receiver operating characteristics curve was higher for men than for women. CONCLUSION: The accuracy of CDT for detection of alcohol abuse in neurological patients was generally low, particularly for women. Combination variables of CDT and gamma-glutamyltransferase did not increase test accuracy. Variables that were associated with higher CDT levels included female sex, antiepileptic drug use, transferrin alterations, and possibly low body mass index. When factors known to cause poor accuracy in particular patient groups are appreciated, CDT may be a good adjunct to the clinical examination. PMID- 11198715 TI - Injury risk among medically identified alcohol and drug abusers. AB - BACKGROUND: Although nonfatal injury prevalence is higher among substance abusers than in the general population, few studies have estimated the injury risk for clinically recognized substance abusers. The extant studies, moreover, analyze rates of visits for injury treatment rather than rates of injury events. This study estimates the excess risk of medically treated and hospitalized nonoccupational injury for people under age 65 with medically identified substance abuse problems and private health care coverage. METHOD: We conducted a retrospective cohort study by using medical claims data from Medstat Systems, Inc., with a longitudinal database of health care claims for 1.5 million people with health care coverage from 70 large corporations. Claims histories for anyone who had an alcohol-related or drug-related primary or secondary diagnosis during 1987 to 1989 were analyzed. A random sample was selected from the remaining people without a substance abuse diagnosis in their medical records. Injury rates were compared among groups. We used logistic regression to estimate odds of medically treated and hospitalized injury, controlling for demographics. RESULTS: Medically identified substance abusers had an elevated risk of injury in a 3-year period; alcohol and drug abusers had the highest risk (58%), followed by drug only abusers (49%), alcohol-only abusers (46%), and controls (38%). Alcohol and drug abusers were almost four times as likely to be hospitalized for an injury in a 3-year period when compared with controls. Injury risks were elevated substantially more for female then male substance abusers. CONCLUSIONS: This study greatly improves on available information about the risk of injury for drug and multiple-substance abusers. Medically identified substance abusers, especially adult women, have a higher probability of injury, more hospitalized injuries, and more injury episodes per person injured than nonabusers. More aggressive identification and subsequent treatment of female substance abusers appear warranted. PMID- 11198716 TI - Genetic influences on craniofacial outcome in an avian model of prenatal alcohol exposure. AB - BACKGROUND: Understanding the basis for ethanol's teratogenic effects may inform the etiology of fetal alcohol syndrome. Here we investigate how genetic background and susceptibility to ethanol-induced neural crest apoptosis contribute to the distinctive craniofacial phenotype observed after prenatal alcohol exposure. METHODS: Nine different chick strains were exposed to ethanol at gastrulation. The sensitivity of these embryos to ethanol-induced neural crest apoptosis was reported elsewhere (Debelak and Smith, 2000). Here, these embryos were permitted to develop until embryonic day 10, when facial morphogenesis was largely complete, and cephalometric measurements were made on cleared skulls. Shifts in facial growth were correlated against the severity of ethanol-induced apoptosis in facial precursors. RESULTS: The facial shape produced by ethanol exposure was a function of the embryos' genetic strain. Three general responses were observed: apparent midfacial flattening (Babcock B300 x Hampshire Red, ISA Babcock, HyLine W98, and HyLine W36 strains), overall facial expansion (Spafas and Babcock B300 strains), or overall facial hypoplasia (DeKalb strains). When dose and timing of exposure were held constant, the embryo's genetic background predicted the facial outcome. For ethanol-sensitive strains, apoptosis of facial precursor populations was required to produce the facial defects. That some strains had essentially normal faces despite extensive cell death indicated a capacity to recover from the earlier neural crest losses. CONCLUSIONS: We propose that ethanol's effects on craniofacial development are multifactoral, and these influences may include susceptibility to apoptosis, regenerative capacity, and compensatory outgrowth of the facial primordia. The embryo's genetic background may modulate these events. The high and low responder chick strains are useful tools to dissect these contributions. PMID- 11198717 TI - Reduced seizure threshold and hippocampal cell loss in rats exposed to alcohol during the brain growth spurt. AB - BACKGROUND: Epilepsy is a prominent sign of neurologic dysfunction in some children with fetal alcohol syndrome (FAS). However, it is unknown whether the epileptic disorders in these children are directly due to the neuroteratogenic effects of alcohol or to some other factor accompanying maternal alcoholism. The hippocampus is vulnerable to alcohol-induced pathologic changes, and dysfunction of the hippocampus often manifests as epilepsy. We examined the effect of alcohol exposure during development on the seizure threshold and examined the relationship between alteration of seizure threshold and alcohol-induced neuronal loss from the hippocampus. METHODS: Rat pups received 0.85, 2.5, or 3.75 g/kg of alcohol via intragastric intubation daily over postnatal days (PD) 4-9. An intubated control and a suckle control group were also included. To assess the effect of a single day of alcohol exposure, an additional group received 3.75 g/kg of alcohol on PD 4 alone. Behavioral seizure thresholds were determined by intravenous infusion of the proconvulsant, pentylenetetrazol (PTZ), on PD 31 or on PD 90. In addition, electrographic seizure thresholds were determined by recording extracellular field potentials from the dentate gyrus. The number of hippocampal CA1 pyramidal cells, CA3 pyramidal cells, and granule cells of the dentate gyrus were determined by stereology. RESULTS: Daily exposure to alcohol resulted in a dose-dependent decrease in the seizure threshold and in the selective loss of CA1 pyramidal cells. Reduction in the seizure threshold was significantly correlated with loss of CA1 pyramidal cells. Recordings of extracellular field potentials confirmed the alcohol-induced reduction in seizure threshold, demonstrated that PTZ-induced seizures involve hippocampal parahippocampal circuitry, and provided evidence that the hippocampal formation is the generator of the PTZ-induced seizures in alcohol-exposed animals. CONCLUSIONS: These findings demonstrate that exposure of the developing brain to alcohol can permanently reduce the threshold for both behavioral and electrographic seizures and can selectively kill hippocampal CA1 pyramidal cells. Both the pathologic findings and the physiologic recordings support the concept that the reduced seizure threshold in alcohol-exposed animals is due to hippocampal pathology. PMID- 11198718 TI - Increased circulating leptin levels in chronic alcoholism. AB - BACKGROUND: Malnutrition seen in chronic alcoholics is partly due to reduced energy intake. Leptin is a peptide hormone implicated in the regulation of appetite and expenditure of energy. The prevalence and significance of abnormal circulating leptin levels in alcoholics, as well as the relationship of these levels with nutritional status, liver disease, and ethanol consumption, remain uncertain. METHODS: Serum leptin levels were measured in 60 active asymptomatic alcoholics, 20 active alcoholics with cirrhosis of the liver, 20 abstinent alcoholics, and 60 controls. Nutritional status and ethanol consumption also were assessed. RESULTS: In the control group, circulating leptin levels (mean 4.7+/ 0.3 microg/liter) correlated with body fat stores. Despite showing a lower fat area of the arm, active alcoholics had significantly higher leptin levels than the controls (p < 0.001), regardless of the presence of cirrhosis. By contrast, none of the abstinent alcoholics showed hyperleptinemia. In the multivariate regression analysis, the fat area of the arm (p < 0.001), the lifetime ethanol consumption (p = 0.007), and the number of cigarettes smoked per day (p = 0.02) were found to be independent factors that influenced leptin levels in active alcoholics. After we adjusted for age, fat area of the arm, and tobacco consumption, a significant correlation was observed between lifetime consumption of ethanol and serum leptin concentrations (r = 0.36, p < 0.001). CONCLUSIONS: Circulating leptin levels are increased in a dose-dependent manner in chronic alcoholism, regardless of nutritional status or the presence of compensated liver disease. PMID- 11198719 TI - Effects of chronic alcohol consumption on the broad phospholipid signal in human brain: an in vivo 31P MRS study. AB - BACKGROUND: Phosphorus magnetic resonance spectroscopy (31P MRS) allows for the measurement of phospholipids and their breakdown products in the human brain. Fairly mobile membrane phospholipids give rise to a broad signal that co resonates with metabolic phosphodiesters. Chronic alcohol exposure increases the rigidity of isolated brain membranes and, thus, may affect the amount and transverse relaxation times (T2) of MRS-detectable phospholipids. We tested the hypothesis that subjects who were heavy drinkers have stiffer membranes than controls who were light drinkers, as reflected in a smaller broad signal component and a shorter T2 of the broad signal in 31P MR spectra of the brain. METHODS: Thirteen alcohol-dependent heavy drinkers (mean age 44 years) were studied by localized 31P MRS in the centrum semiovale and compared with 17 nondependent light drinkers of similar age. The broad component signal was separated from the metabolite signal by convolution difference, which is based on the large difference in line widths of these two signals. Longitudinal and T2 relaxation times were measured using standard methods. RESULTS: The broad component integral was 13% lower in the brain of heavy drinkers compared with light drinkers (p < 0.001) and remained significantly smaller after corrections for both longitudinal and transverse relaxations (p < 0.01). The T2 distribution of the broad component consistently showed two resolvable components in both groups. The fast relaxing component had the same T2 in both groups (T2 = 1.9 msec). The slower relaxing component T2 was 0.6 msec shorter in heavy drinkers compared with light drinkers (p = 0.08). CONCLUSIONS: These results, observed in the absence of white matter volume loss, are consistent with biochemical alterations and higher rigidity of white matter phospholipids associated with long-term chronic alcohol abuse. The observed smaller broad signal component in these relatively young heavy drinkers is a sensitive measure of white matter phospholipid damage. PMID- 11198720 TI - Pretreatment with hydromorphone, a mu-opioid agonist, does not alter the acute behavioral and physiological effects of ethanol in humans. AB - BACKGROUND: Endogenous opioid systems are thought to mediate at least some of the behavioral effects of ethanol. Opioid antagonists, like naloxone and naltrexone, decrease ethanol self-administration under a variety of conditions in different species of laboratory animals (e.g., rodents and nonhuman primates). Opioid agonists, like morphine, also alter ethanol consumption. However, the dose response functions for opioid agonists are complex in that low doses increase ethanol self-administration, whereas moderate to high doses decrease ethanol self administration. The results of prospective human laboratory studies that assessed the behavioral effects of ethanol after pretreatment with an opioid antagonist are mixed. The aim of the present study was to assess the acute subject-rated effects of ethanol (0, 0.5, and 1 g/kg) after pretreatment with hydromorphone, a mu-opioid agonist. METHODS: In the present experiment, the acute subject-rated, performance-impairing, and physiological effects of ethanol (0, 0.5, and 1 g/kg) were examined after pretreatment with hydromorphone (0, 1, and 2 mg), a mu-opioid agonist, in nine healthy volunteers. Volunteers received one of the nine possible ethanolhydromorphone combinations during each of nine experimental sessions. RESULTS: Ethanol produced prototypical subject-rated drug effects (e.g., dose dependently increased ratings of "high"), impaired performance, and increased heart rate. Hydromorphone pretreatment generally did not significantly alter the subject-rated, performance-impairing, or physiological effects of ethanol. CONCLUSIONS: The results of the present experiment suggest that hydromorphone pretreatment does not significantly affect the subject-rated effects of ethanol. Future human laboratory studies should test higher doses of hydromorphone. Future studies also might use more sophisticated behavioral procedures like self administration, or perhaps drug discrimination, to determine if opioid agonists can modulate the behavioral effects of ethanol in humans. PMID- 11198721 TI - Effect of repeated exposure to alcohol on the response of the hypothalamic pituitary-adrenal axis of the rat: I. Role of changes in hypothalamic neuronal activity. AB - BACKGROUND: Prior (3-12 days) injection of alcohol significantly blunts the response of the hypothalamic-pituitary-adrenal (HPA) axis to a second drug challenge without measurably altering responses to other stressors. We therefore determined whether adaptation in hypothalamic neurons underlies this decreased activity. METHODS: Adult male rats were administered alcohol (4.5 g/kg intragastrically) or vehicle daily for three consecutive days and then were challenged with the vehicle or alcohol 7 days later. Levels of adrenocorticotropin hormone (ACTH) in the circulation, corticotropin-releasing factor (CRF), CRF receptors type 1 (CRFR1) and vasopressin (VP) transcripts in the paraventricular nucleus (PVN) of the hypothalamus, and CRF/VP peptide in the median eminence were measured. RESULTS: Resting PVN levels of CRF, CRFR1, and VP were comparable in all animals on day 7 of recovery, whereas CRF and VP stores in the external zone of the median eminence were decreased in animals previously exposed to alcohol. After the acute alcohol challenge on day 7, rats previously exposed to the drug exhibited a significant (p < 0.01) dampening of their PVN CRF and CRFR1, but not VP neuronal response, compared with vehicle-pretreated rats. CONCLUSION: Blunted neuronal activity of PVN CRF neurons may be responsible for the decreased ACTH response that we previously reported in rats that had been injected with alcohol several days earlier. In addition, and despite comparable PVN VP transcript levels, the lower levels of this peptide in the median eminence also may participate in the blunted ACTH response that we observed. PMID- 11198722 TI - Sexual dysfunction and cardiovascular disease: a transatlantic consensus. PMID- 11198723 TI - Difficulties in interpreting the results of carotid endarterectomy: the importance of prospective independent audit. PMID- 11198724 TI - The dogma of identifying occult bacterial infections in young febrile children: a survey of primary-care physicians. AB - Management of undifferentiated febrile illness in young children continues to be a controversial issue among primary-care physicians. A self-administered questionnaire was mailed to 600 randomly selected physicians regarding their management of children with high fever and no focus of infection at various ages: 3 weeks, 7 weeks, 4 months and 20 months. Completed questionnaires were returned by 419 (70%) physicians. Nearly 77% of physicians would hospitalize a 3-week old infant with fever and 70% would treat these infants empirically with antibiotics. Sixty-one per cent of physicians would hospitalize a 7-week-old infant with fever and 46% would treat empirically with antibiotics. Approximately 80% and 93% of physicians, respectively, would not hospitalize 4- and 20-month-old infants with high fever and no focus of infection, but 72% and 59%, respectively, would treat such infants with antibiotics. There was considerable variation in the way physicians managed young febrile children with no focus of infection and the clinical approach of some physicians was remarkably different from current knowledge and recommendations. PMID- 11198725 TI - Relief of sore throat with the anti-inflammatory throat lozenge flurbiprofen 8.75 mg: a randomised, double-blind, placebo-controlled study of efficacy and safety. AB - In this double-blind study, 301 patients with subjective and objective signs of sore throat were randomly assigned to flurbiprofen 8.75 mg (n = 129), flurbiprofen 12.5 mg (n = 43) or placebo (demulcent lozenge without active drug [n = 129]). Efficacy was assessed by changes in subjective rating scales primarily after a single dose and also over a 4-day period. Flurbiprofen 8.75 mg was superior to placebo in a number of efficacy parameters, notably throat soreness. Throat soreness was significantly reduced after 15 minutes (p < 0.05), with effects sustained for at least 2 hours (p < 0.05). Multiple dosing with flurbiprofen 8.75 mg lozenges continued to provide effective symptomatic relief over the 4-day treatment period. The small sample size was considered contributory to the variable results obtained with flurbiprofen 12.5 mg lozenges, but overall these were not inconsistent with previous trials. Both treatments were tolerated well. Flurbiprofen 8.75 mg lozenges provide an effective and well tolerated treatment for sore throat. PMID- 11198726 TI - Moxifloxacin versus cephalexin in the treatment of uncomplicated skin infections. AB - The efficacy and safety of oral moxifloxacin (400 mg once daily, 7 days) versus cephalexin (500 mg three times daily, 7 days) were compared in a prospective, multicentre, randomised, double-blind trial in 401 adults with uncomplicated skin infections. Clinical outcome was evaluated in 351 patients. Moxifloxacin proved to be as effective as cephalexin both clinically (90% versus 91%, respectively) and bacteriologically in eradicating the most frequently isolated pathogen Staphylococcus aureus (92% and 93%, respectively). Moxifloxacin was more effective than cephalexin in eliminating Streptococcus spp. (90% and 82%, respectively). Drug-related adverse events were comparable in both treatment groups with the most frequently reported being nausea in the moxifloxacin-treated patients and headache in the cephalexin-treated patients. Medication was discontinued due to unwanted reactions in 3% of the moxifloxacin- and 4% of the cephalexin-treated patients. Moxifloxacin, 400 mg once daily for 7 days, is as safe and effective as cephalexin 500 mg three times daily for 7 days in the treatment of uncomplicated skin infections. PMID- 11198727 TI - Can prophylactic oral erythromycin reduce time to full enteral feeds in preterm neonates? AB - Efficacy of oral, prophylactic erythromycin in reducing the time to establish full enteral feeds (150 ml/kg/day) was assessed in neonates < 32 weeks, ready for enteral feeds. Seventy-three consecutive neonates were randomised to receive oral erythromycin ethyl succinate (n = 36) or placebo (n = 37) in a double-blind trial until full enteral feeds or 14 days of therapy were reached. A prospectively designed feeding regimen, including plan of action for signs of feed intolerance, was common for all enrolled neonates. The median gestational age, birth weight and postnatal age at start of feeds were 29 versus 30 weeks (p = 0.40), 1232 versus 1280 g (p = 0.96) and 5 versus 5 days (p = 0.84) for erythromycin and placebo group, respectively. Time to achieve full feeds was not significantly different in the two groups. (median times: erythromycin 93.5 versus placebo 104 hours, p = 0.60). Erythromycin-related side-effects did not occur. PMID- 11198728 TI - A comparison of nisoldipine ER and amlodipine for the treatment of mild to moderate hypertension. AB - This multicentre, double-blind, double-dummy, randomised trial compared the efficacy and tolerability of nisoldipine extended release (10-40 mg) and amlodipine (2.5-10 mg) in 161 patients. The primary end point was a between treatment comparison of change from baseline to week 8 in mean office diastolic blood pressure (DBP). The least squares mean reductions in systolic (S)BP/DBP (+/ standard error) for nisoldipine and amlodipine were -11.7/-9.3 +/- 1.4/0.8 and 14.3/-12.0 +/- 1.4/0.8 mmHg, respectively. The DBP treatment difference was 2.7 mmHg (90% confidence interval: 1.1 to 4.3 mmHg; p = 0.005). Tolerability profiles were similar between treatments. The drug acquisition cost per mmHg DBP reduction was 40% lower with nisoldipine; an acquisition cost analysis revealed that amlodipine was 80% more expensive than nisoldipine for treating hypertension. In summary, nisoldipine and amlodipine provide clinically equivalent antihypertensive efficacy; however, nisoldipine is more economical than amlodipine. PMID- 11198729 TI - Prognostic value of CT scan features in acute ischaemic stroke and relationship with clinical stroke syndromes. AB - The aim of this prospective study was to investigate the value of CT scan in prognosis of acute ischaemic stroke patients as a variable additional to clinical stroke syndromes to develop a simple classification of CT scan features to provide a practical approach to prognosticate and manage such patients. One hundred and eight nine patients admitted with ischaemic stroke were investigated with a CT scan. CT scan features were classified into two groups: large infarct, LI (across more than one lobe) and non-large infarcts (N-LI) for all other features. Patients were also studied for clinical syndromes, analysing results for total anterior circulation syndrome (TACS). Outcome was measured as early post stroke Barthel index, acute phase and 3-month mortality. Patients with LI had features of severe strokes and had a lower Barthel index (p < 0.001), lower Glasgow coma score (p < 0.001), more association with incontinence (p < 0.001), pyrexia (p = 0.007) and dysphagia (p < 0.001). LI patients required higher level of care in acute wards and had a higher length of stay (p = 0.01). Both the LI and TACS individually had a significantly higher mortality (p < 0.001) and similar positive predictive value, sensitivity and specificity for 3-month mortality. While the combined factor of 'large infarct and TACS' provided the highest likelihood ratio (3.1) for mortality, the factor of 'large infarct or TACS' was the most sensitive (85%) to identify majority of patients at a risk of mortality. N-LI patients had a better prognosis. Classification of cerebral infarcts into large and non-large categories identifies patients who require higher level of care in acute wards and have a higher mortality. Combined factor of 'large infarct and/or TACS' identifies the majority of patients at risk of 3 month mortality as compared to either variable taken individually. CT scan features are complimentary to clinical syndromes for managing acute stroke patients. PMID- 11198731 TI - Axillary arch and its implications in axillary dissection--review. AB - Axillary arch is an anomalous muscular slip of latissimus dorsi muscle occasionally encountered in axillary dissection. A systematic review of medical literature published between 1966 to 1999 was performed regarding its incidence, clinical features and management. Its presence in axillary dissection should be recognised to avoid confusion in staging of lymph nodes and to prevent injury to axillary vessels and brachial plexus. PMID- 11198730 TI - Catecholamine secretion and ploidy in phaeochromocytoma. AB - The aim was to evaluate 24 hr urine catecholamine, HMMA and HVA excretion in relation to ploidy in phaeochromocytoma. Data from five diploid and nine tetraploid tumours showed a significant reduction in urine noradrenaline (p = 0.02) and HMMA (p = 0.03) in diploid tumours but no difference in adrenaline, dopamine and HVA excretion using the Mann-Whitney U test. None of the patients showed recurrence after a mean of 5.7 years of follow up. A review of published ploidy studies in phaeochromocytoma shows that malignancy is more than six times more common in non-diploid tumours but diploidy does not equate with benignity. No biochemical marker is a reliable index of malignancy. All patients should undergo lifetime review for recurrence. PMID- 11198732 TI - Skeletal muscle relaxants: pharmacodynamics and pharmacokinetics in different patient groups. AB - Muscle relaxants can be safely administered during anaesthesia, providing the basic pharmacodynamic and pharmacokinetic characteristics of the compounds together with the physiological status of the patient are known. In this review the pharmacodynamics and pharmacokinetics of the neuromuscular blocking agents are discussed and related to the physical health or disease state of groups of patients. PMID- 11198733 TI - Diabetes knowledge--are patients getting the message? AB - Diabetes knowledge in a multi-ethnic population was assessed in 161 insulin treated diabetic patients using a 21-point multiple choice questionnaire translated into the appropriate languages. Our data showed a significant difference in diabetes knowledge related to ethnicity, being less in Asians and Afro-Caribbeans groups compared to Caucasians. In all groups there was a negative correlation with age, with older adults achieving lower scores. Gender and duration of disease did not appear to influence knowledge scores. This information has implications for the way in which we deliver our diabetes educational programme to ethnic minority groups and the elderly. PMID- 11198734 TI - Esomeprazole, a new proton pump inhibitor: pharmacological characteristics and clinical efficacy. AB - Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor synthesised as an optical isomer to become available for clinical use. Esomeprazole is optically stable in humans with negligible inversion to the R isomer. Esomeprazole has significantly higher oral bioavailability than omeprazole, resulting in greater acid suppression. In clinical studies, 4 weeks' treatment with 40 mg esomeprazole demonstrated greater healing of all grades of erosive oesophagitis, compared with 20 mg omeprazole (76-82% versus 69-71%) and higher rates of symptom resolution (65-68% versus 58-61%) Furthermore, esomeprazole maintained healing rates of up to 90% over 6 months in erosive oesophagitis. Comparisons with other proton pump inhibitors in oesophagitis are, as yet, unavailable. In patients with endoscopy-negative gastro-oesophageal reflux disease (GERD), on-demand therapy with esomeprazole 20 mg has been shown to be very efficacious compared with placebo, and is well tolerated; however, comparisons with other proton pump inhibitors have not been performed. Long-term use of esomeprazole for up to 12 months in patients with GERD have not raised any significant safety concerns with respect to the development of atrophic gastritis or clinically relevant changes in enterochromaffin-like cells. PMID- 11198735 TI - Myocardial bridging. AB - We present a case of myocardial bridging, which was seen following urgent cardiac catherisation for post-infarction unstable angina in a 55-year-old man who was initially admitted with an acute inferior myocardial infarction. PMID- 11198736 TI - Progressive heart block in active rheumatoid arthritis. AB - A 68-year-old woman presented with active rheumatoid arthritis (RA) and severe extra-articular manifestations. During the course of her treatment, her electrocardiogram (ECG) transformed from normal sinus rhythm to left bundle branch block and finally to complete heart block (CHB). Investigations ruled out an ischaemic event. A permanent pacemaker was inserted due to the symptoms of heart failure and she made an uneventful recovery. CHB in RA is probably a marker of severity of the disease. PMID- 11198737 TI - A case of haemophagocytic syndrome and Kikuchi-Fujimoto disease occurring concurrently in a 17-year-old female. AB - An unusual case in which a young Asian female presenting with fever, lymphadenopathy and cytopaenia was found to have distinct histological features of both haemophagocytic syndrome (HS) and histiocytic necrotising lymphadenitis (Kikuchi-Fujimoto disease, KFD) is presented. We review the clinical features of each of these rare, but important, diagnoses and propose the hypothesis that they may form part of a disease continuum, rather than representing separate entities. PMID- 11198738 TI - Catastrophic antiphospholipid syndrome presenting as dilated cardiomyopathy with bilateral branch retinal artery thrombosis. AB - Cardiac manifestation of antiphospholipid syndrome (APS) is mainly in the form of left-sided valvular insufficiency, intra-cardiac thrombi or coronary artery occlusion. Dilated cardiomyopathy is a rare but important cardiac manifestation of APS, and responds well to adequate anticoagulation and steroids. We describe a case in which APS presented with dilated cardiomyopathy and bilateral retinal artery thrombosis. PMID- 11198739 TI - Mesenchymal hamartoma of the liver in an adult: a review of the literature. AB - Mesenchymal hamartoma of the liver is an unusual oncologic entity which occurs almost exclusively in infancy and childhood; fewer than 200 cases have been reported. We present the case of a 21-year-old female, who was admitted to our institution with a painful right subcostal mass lasting for 6 months, who had no evidence of generalised disease. Imaging procedures revealed a central solid lesion, 15 cm in diameter, in the right lobe of the liver, with cystic degeneration. The patient underwent a formal right hepatectomy. The pathology report ascertained the presence of a benign mesenchymal hamartoma of the liver. PMID- 11198740 TI - Mitral valve prolapse, panic attack and chest pain. PMID- 11198741 TI - Who should do thyroid surgery? PMID- 11198742 TI - Postnatal care: no time for complacency. PMID- 11198743 TI - Neuropathic pain. AB - Neuropathic pain is a distressing, poorly understood and under-treated condition. In this review we seek to examine the definition and classification of neuropathic pain, summarize clinically important underlying mechanisms, outline current management strategies and look at future directions for research and therapy. PMID- 11198744 TI - Pitfalls in the diagnosis of motor neurone disease. AB - Motor neurone disease is characterized by progressive degeneration of upper and lower motor neurones with preservation of cognition. Recognition of classical motor neurone disease is not difficult, but during the early stages both false positive and false negative diagnoses are common. Careful examination, frequent follow-up and ancillary tests are necessary to avoid erroneous diagnoses. PMID- 11198745 TI - The treatment of malignant cerebral tumours. AB - Malignant cerebral tumours are uncommon. While a large proportion are resistant to conventional therapies there are a significant number of curable malignant brain tumours that require recognition and appropriate therapy. PMID- 11198746 TI - Management of toxic epidermal necrolysis. AB - Toxic epidermal necrolysis and Stevens-Johnson syndrome are rare, life threatening drug reactions. Widespread epidermal necrosis and mucosal erosions lead to complications similar to those developing after extensive burns. Treatment is supportive. The role of steroids and other potential disease modifying agents remains to be established by controlled studies. PMID- 11198747 TI - The use of Scopoderm in palliative care. AB - The drug hyoscine has several indications for symptom control for patients with end-stage disease. The transdermal preparation, Scopoderm, is most widely used to control excess salivary secretions but it can also have a role in the management of terminal secretions and in the control of nausea. PMID- 11198748 TI - Zyban: an effective treatment for nicotine addiction. AB - Recent research has identified nicotine as a powerfully addictive substance. This article outlines how the new non-nicotine smoking cessation drug, Zyban, can help people to break the cycle of addiction and stop smoking. PMID- 11198749 TI - Statins: where are we now? AB - Statin therapy reduces the risk of cardiac events by 30% in both primary and secondary prevention. Although fine-tuning of the evidence will occur as more clinical trials report, the challenge is now to implement the evidence to the benefit of patients. PMID- 11198750 TI - The management of alcohol-related seizures: an overview. AB - Alcohol-withdrawal seizures are one of the common medical emergencies. The seizures are generalized and usually occur abruptly between 6-8 hours after cessation of alcohol use (peak 12-24 hours). These patients are often uncooperative and therefore need careful assessment. Lorazepam is the first-line drug for termination and prophylaxis of alcohol-withdrawal seizures. PMID- 11198751 TI - Sample size determination in clinical research: 2. AB - In the second of this two-part series, comparative study design is considered and, using examples, power calculation is explained. The information required for calculating sample size for comparative studies is highlighted. PMID- 11198752 TI - Finding health information on the Internet: health consumers. AB - The quality of health information on the Internet is extremely variable. This article highlights some of the problems consumers encounter when searching for health information and suggests ways in which these can be overcome. PMID- 11198753 TI - Resolution of nephrotic syndrome caused by amyloidosis following surgery for Crohn's disease. PMID- 11198754 TI - Renal cell carcinoma presenting with cardiac failure. PMID- 11198755 TI - An unusual case of recurrent septicaemia. PMID- 11198756 TI - Who should do thyroid surgery? PMID- 11198757 TI - Management of the acute abdomen. PMID- 11198758 TI - Management of flail chest. PMID- 11198759 TI - Ethics and regulation in neurosurgical practice. PMID- 11198760 TI - Good practice: a guide for neurosurgeons. PMID- 11198761 TI - Principles of gene therapy: potential applications in the treatment of cerebral ischaemia. AB - In this review we explore gene therapy as a possible treatment for conditions causing cerebral ischaemia and briefly consider other neurological pathologies such as brain tumours. DNA transfer may be achieved using retrovirus, herpes simplex virus, adenovirus, and adeno-associated virus vectors or liposomes. After cerebral ischaemia, these vectors are used to upregulate genes that increase survival and inhibit those that promote death in the injured cells. In contrast, in brain tumours gene therapy aims to kill the target cells. Examples from studies using cell culture, animal models and patients are presented. We conclude that manipulation of gene expression has potential for the treatment of cerebral ischaemia and brain tumours, although, at present, there are formidable technical obstacles to be overcome before clinical applications become a reality. PMID- 11198762 TI - Depression: a role for neurosurgery? AB - After providing an overview of depression this article briefly reviews the development of psychosurgery and outlines the current procedures in use world wide. Stereotactic subcaudate tractotomy (SST) is described in particular detail, and the rationale for its use in the treatment of resistant depression is then discussed by considering the findings of neuropsychological, neurophysiological and neuroimaging studies. The emerging evidence suggests that the prefrontal cortex subserves an essential function in emotion and that disruption of its connections modifies mood. PMID- 11198763 TI - The cause and incidence of secondary insults in severely head-injured adults and children. AB - The cause and incidence of reductions in cerebral perfusion pressure, and rises in intracranial pressure have been examined in a series of patients with severe head injury defined as an initial Glasgow Coma Sum of less than or equal to 8. Two-hundred-and-seven adults (aged over 16 years) and 84 children admitted to Newcastle General Hospital, who had intracranial pressure monitoring as part of their routine management, were studied. Intracranial pressure (ICP), arterial pressure and cerebral perfusion pressure (CPP) were sampled and recorded every 2 min. Patients' CT findings were classified into distinct groups using the method described by Marshall. Secondary insults were defined using the Edinburgh University Secondary Insult Grades (EUSIG) and the incidence and cause (raised ICP, reduced CPP or a combination of the two) was established. Outcome was assessed at 6 months using the Glasgow Outcome Scale. In the majority of adults with head injury it is the combination of reduced arterial pressure and raised ICP that contributes to the reduction in cerebral perfusion pressure. This was not the case for Diffuse Injury Type I. In children similar characteristics were found across each of the CT classifications. The vast majority of falls in CPP down to 60 mmHg were caused by reduced arterial pressure. Reductions below 50 mmHg were almost always due to a combination of both reduced arterial pressure and raised ICP. The results in adults were similar, but not identical, to those of the paediatric cases. Diffuse Injury Type I stood out from all the other categories as the only one where reductions in perfusion pressure were almost exclusively due to reductions in arterial pressure and not to increases in ICP. The management of these patients should ensure the adequacy of perfusion pressure by maintaining arterial pressure at a satisfactory level. These results suggest that vigilant monitoring of both intracranial pressure and arterial pressure is required to lower the incidence of secondary insults. PMID- 11198764 TI - Endoscopic transsphenoidal pituitary surgery: various surgical techniques and recommended steps for procedural transition. AB - Various techniques in pituitary endoscopy are reviewed in the attempt to assemble the transitional steps necessary to take a neurosurgeon from traditional microscopic transsphenoidal surgery to endoscopic endonasal pituitary surgery. The senior author's (HDJ) experiences of endonasal endoscopy in more than 200 operations as well as the reports in the literature on pituitary endoscopy are reviewed. Two distinct advantages that an endoscope has over an operating microscope are its ability to visualize through a narrow surgical corridor and its ability to provide angled, close-up views. An endoscope can be used to assist the operating microscope (endoscope-assisted microsurgery). Endoscopy can also be used for endonasal retractor placement when microscopic surgery is preferred (endoscopic sphenoidotomy). When endonasal endoscopy is chosen, the surgical approach can be made with a deep-transseptal, a paraseptal, a middle turbinectomy or a middle meatal approach (endonasal transsphenoidal endoscopy). Endonasal endoscopy can be performed via either one or two nostrils. Working-channel endoscopy can be performed for restricted purposes. When a neurosurgeon desires to adopt endoscopy into pituitary surgery, the author recommends endoscope assisted microsurgery as the first step followed by endoscopic sphenoidotomy as a combined effort between an endoscopic rhinologist and the neurosurgeon as the next step leading finally to endonasal pituitary endoscopy. Various methods of transsphenoidal endoscopy and the authors' recommendations for transitional steps are reported based on the authors' personal experience and literature review. PMID- 11198765 TI - Prediction of cerebral ischaemia during carotid endarterectomy with preoperative CO2-reactivity studies and angiography. AB - The objective of this study was to assess the value of combining the preoperative CO2 cerebrovascular reactivity index (CO2RI) with carotid and cerebral angiography in predicting the risk of severe cerebral ischaemia (SCI) during carotid endarterectomy (CEA). Seventy-four consecutive patients scheduled for CEA underwent preoperative digital subtraction angiography and CO2-reactivity tests. During CEA, cerebral function monitor (CFM) was used to document cortical electrical activity, whilst transcranial Doppler measured the middle cerebral artery flow velocity (FV). A persistent fall in CFM voltage and/or a fall in FV > or = 60% on internal carotid artery (ICA) clamping were used as criteria for defining SCI. Complete data from 59 patients were obtained for final analysis. Twelve cases showed a fall in FV > or = 60%; 11 of these also showed a sustained fall in CFM voltage. Using logistic regression, the risk of SCI was found to be negatively associated with (1) contralateral CO2RI, (2) the percentage stenosis of the contralateral ICA, and (3) the difference between ipsilateral and contralateral CO2RI. Using these factors, a logistic regression model for predicting the risk of SCI was established which provided a sensitivity of 75% and specificity of 100%. The risk of SCI during CEA was related to the contralateral ICA stenosis and the CO2RI of both cerebral hemispheres. This information may assist in presurgical planning and help to select asymptomatic carotid lesions for surgery. PMID- 11198766 TI - Intracerebral haemorrhage and drug abuse in young adults. AB - The epidemic of abuse of the so-called 'designer drugs' amphetamine, cocaine and ecstasy--is fast replacing traditional aetiological factors as the largest cause of intracerebral haemorrhage among young adults. Traditional teaching is that these represent hypertensive haemorrhages. Recent reports, however, have indicated that these patients may harbour underlying vascular malformations. We review 13 patients with a positive history of drug abuse preceding the onset of intracerebral haemorrhage. These patients presented to the National Hospital for Neurology and Neurosurgery in central London over a 7-month period. Of the 13 patients (eight male, five female), average age 31 years (19-43) years), 10 were well enough to undergo cerebral angiography. Intracranial aneurysms were demonstrated in six patients and arteriovenous malformations in three patients. In only one of the patients was the angiogram normal. A further patient was subsequently shown to have a middle cerebral artery aneurysm at autopsy. The epidemiology, pharmacology and systemic effects of these drugs are considered. The mechanisms by which these compounds cause intracerebral complications and their influence on prognosis are discussed. The incidence of intracerebral haemorrhage (ICH), ischaemic cerebral infarctions and subarachnoid haemorrhage (SAH) following drug abuse is increasing. Contrary to historical opinion, drug related ICH is frequently related to an underlying vascular malformation. Arteriography should be part of the evaluation of most young patients with nontraumatic ICH. A thorough history focusing on the use of illicit substances and toxicological screening of urine and serum should be part of the evaluation of any young patient with a stroke. PMID- 11198767 TI - Third ventricular cysts and membranes unsuspected on conventional CT and MRI. AB - Three cases are presented of symptomatic cysts or membranes within the third ventricle interfering with CSF flow and presenting as non-communicating triventricular hydrocephalus. None was visible on conventional CT or MRI, two being discovered at neuroendoscopy and one only with a specific MRI sequence designed to show CSF partitioning. PMID- 11198768 TI - Prothrombin complex concentrate for oral anticoagulant reversal in neurosurgical emergencies. AB - The incidence of spontaneous intracranial haemorrhage has increased markedly in line with the increased use of oral anticoagulant agents. Recent guidelines for reversal of this acquired coagulation defect in an emergency have been established, but they are not adhered to in all centres. Our unit is referred between 20 and 60 patients per year (1994-1999) who are anticoagulated and require urgent neurosurgical intervention. In order to investigate this, we performed a prospective study using prothrombin complex concentrate (PCC). PCC was given to the first six patients with intracranial haemorrhage admitted to the neurosurgical unit requiring urgent correction of anticoagulation (Group 1) and compared with patients receiving standard treatment with fresh frozen plasma and vitamin K (Group 2). Mean International Normalised Ratios of Group 1 were 4.86 pretreatment and 1.32 posttreatment, and of Group 2 were 5.32 and 2.30, respectively. Results for complete reversal and reversal time were significant for PCC with p < 0.001. We recommend PCC for rapid and effective reversal of warfarin in life-threatening neurosurgical emergencies. PMID- 11198769 TI - Ventriculo-atrial shunt insertion: pressure monitoring as an aid to accurate placement. AB - The objective of this paper is to describe a new method to ensure accurate placement of a ventriculo-atrial shunt distal catheter. A technique is described using pressure waveform changes within the right side of the heart. Pressure monitoring is a new method of placing atrial catheters and is easy to perform. PMID- 11198770 TI - Microvascular Doppler ultrasound-assisted neuroendoscopic surgery. AB - To achieve endoscopic procedures more safely and less invasively, an operative strategy with ultrasound-assisted neuroendoscopic surgery is described. The improvement in the endoscope unit is that endoscopic viewing can be stopped on the display, anytime we choose and simultaneously visualize the ongoing view on the same display. The ultrasound unit, using a miniature Doppler probe, is to able to detect even invisible vessels in real-time, easily and non-invasively. The information from both units can be switched intraoperatively, whenever required. PMID- 11198771 TI - Use of a non-penetrating staple device for spinal dural closure. AB - Closure of the spinal dura by suture can be technically demanding and a watertight closure is rarely achieved. A method of dural closure using non penetrating staples is described which permits rapid watertight closure of the dura even in confined spaces. PMID- 11198772 TI - Multimodality monitoring and the diagnosis of traumatic caroticocavernous fistula following head injury. AB - Increases in jugular bulb saturations (SjO2) following head injury are usually due to hyperaemia. Less commonly this may be due to the development of an arteriovenous fistula. We describe how SjO2 monitoring can be used in conjunction with transcranial Doppler ultrasound to make the distinction between these two conditions, which require distinct therapies. Multimodality monitoring in acute injury provides information regarding underlying pathophysiology and permits individualization of therapy. PMID- 11198773 TI - Spinal extradural angiolipoma. AB - We report a case of spinal angiolipoma, causing paraplegia in a 38-year-old pregnant female. The tumour was excised and the patient made remarkable recovery. The role of pregnancy and its associated hormonal profiles on tumour growth is discussed. PMID- 11198774 TI - Metastatic prostate adenocarcinoma of the dura mater. AB - A 70-year-old man with known metastatic prostate carcinoma to the long bones of the lower extremities, presented with a several day history of lethargy and confusion. CT was interpreted as showing bilateral acute and chronic subdural hematomas (SDH). Upon opening the dura, a yellowish, firm tumor was layered over the frontal convexity. No hematoma was found. Histological examination revealed prostate carcinoma. PMID- 11198775 TI - Intramedullary spinal cord metastases from a hypernephroma 11 years following the diagnosis and treatment of the primary lesion. AB - Intramedullary spinal cord metastases are rare. An intramedullary spinal cord metastasis of renal origin, presenting 11 years after the diagnosis of the primary lesion, is reported. PMID- 11198776 TI - Heterotopic bone formation causing recurrent donor site pain following iliac crest bone harvesting. AB - An unusual case of recurrent iliac crest donor site pain secondary to heterotopic bone formation is described. The literature is reviewed with a special emphasis on the aetiology and treatment of this entity. PMID- 11198777 TI - Rupture of an internal carotid artery aneurysm in the petrous temporal bone. AB - A case of otorrhagia following the rupture of an aneurysm of the intrapetrous portion of the internal carotid artery is presented. The aneurysm was successfully treated by balloon occlusion of the parent artery. The problems associated with diagnosis and clinical management of these lesions is discussed and possible solutions suggested. PMID- 11198778 TI - Spinal teratoma: is there a place for adjuvant treatment? Two cases and a review of the literature. AB - Spinal teratomas are rare intradural spinal tumours, commonly of benign histological profile. The main treatment remains surgical excision which often is incomplete as the tumour is frequently intimately related to surrounding nerve roots and adjacent spinal cord. The value of adjuvant treatment in the form of radiotherapy has not been clearly identified. We report two patients with spinal teratomas in the lower thoracic and conus region, who were treated with surgical excision and did not receive radiotherapy. One of the tumours recurred at 38 months following surgical excision and required a second operation. We review in addition another 20 patients reported in the literature with such tumours. With a mean follow-up of 25 months a local recurrence rate of 10% was observed, the same in both total and subtotal excision groups. No deaths were reported. Analysis of cumulative survival from surgery to treatment failure demonstrated that recurrence occurs late, verifying a slow biological progression of this tumour type. Although no reliable information of the effect of radiotherapy can be obtained, it is difficult to see how radiotherapy could have an impact on such a slow growing tumour. Initial treatment of choice remains surgical excision. If the teratoma shows any malignant histological features or germ cell elements radiotherapy should be employed after surgical excision, even if apparently totally excised. In the presence of benign histology it would seem appropriate to avoid radiotherapy after initial surgery. In case of tumour recurrence or progression to explore the possibility of further surgery first, before considering radiotherapy which even then may have doubtful efficacy. PMID- 11198779 TI - Split cord malformation and neurenteric cyst--case report and a theory of embryogenesis. AB - A rare case of split cord malformation with neurenteric cyst is presented. The clinical, radiological and surgical findings are presented, and the possible embryological basis is discussed. To our knowledge, only seven such cases have been reported in the literature. PMID- 11198780 TI - Intracranial plasma cell granuloma--a case report and review of the literature. AB - We report a case of plasma cell granuloma which is a rare intracranial tumour showing plasma cell infiltration. It mimics meningioma and solitary plasmacytoma clinically and radiologically. Clinical presentation, diagnostic investigations and management are discussed with a review of the literature. PMID- 11198781 TI - Intrathecal migration of a lumboperitoneal shunt. PMID- 11198782 TI - Detection of Kernohan's notch on magnetic resonance imaging in a patient with acute subdural haematoma. PMID- 11198783 TI - Dietary fibre and ischaemic heart disease. PMID- 11198784 TI - Is dietary fiber beneficial in chronic ischemic heart disease? AB - OBJECTIVES: To evaluate the benefit of a dietary fiber preparation (Fibernat) in patients with chronic ischemic heart disease (IHD). METHODS: From January 1997 to March 1998, 114 consecutive patients with chronic IHD were enrolled in this prospective double blind randomized placebo controlled trial. The fiber (F) and placebo (P) groups were comparable at baseline. All patients were given advice regarding dietary and lifestyle modifications. Concomitant drug therapy was not altered. The drug (consisting of soluble and insoluble fibers obtained from fenugreek, guar gum and wheat bran) and placebo were administered for six months (10 grams twice daily). RESULTS: The following parameters improved in both groups: HDL cholesterol (32 to 39 mg/dl, p < 0.0009 in F and 33 to 38, p < 0.007 in P), total: HDL cholesterol ratio (6.7 to 5.6, p < 0.0007 in F and from 7.0 to 6.0, p < 0.01 in P) and weight (64.0 to 63.0 kg, p < 0.002 in F and 60.3 to 59.5, p < 0.002 in P). The Apolipoprotein B increased (101 to 129 mg/dl, p < 0.00001 in F and 98 to 127, p < 0.0008 in P). The following parameters improved only in group F: LDL cholesterol (146 to 134, p < 0.027), Apolipoprotein A-1 (105 to 139, p < 0.001), body mass index (24.9 to 24.5, p < 0.03) and waist circumference (37.2 to 36.7, p < 0.03). Total cholesterol, VLDL cholesterol, triglycerides, hip circumference, W:H ratio, exercise time and blood sugar were unchanged in both groups. CONCLUSIONS: Fibernat is well tolerated, safe and had favorable effects on LDL cholesterol, Apolipoprotein A-1, body mass index and waist circumference. PMID- 11198785 TI - Epidemic dropsy--a clinical study of the Delhi outbreak. AB - BACKGROUND: A major outbreak of epidemic dropsy occurred in Delhi, India, in August-September 1998, due to the consumption of contaminated mustard oil. METHODS: The clinical data of 212 adult patients of epidemic dropsy who presented to our hospital is analysed. RESULTS: Pitting pedal oedema (100%), skin erythema (75%), limb tenderness (63%), diarrhea (51%) and hepatomegaly (34%) were the prominent clinical manifestations observed in the patients. Superficial retinal haemorrhages and retinal venous dilatation was observed on fundus examination and 9% of patients developed an open angle glaucoma over a three month follow up period. Cardiac failure was present in 14% of patients. Most patients had mild disease which responded to cessation of mustard oil consumption, bed rest, diuretics and antioxidants. There were six deaths, all of whom had intractable cardiac failure. A unique feature of this outbreak was the documentation of acute renal failure in three patients, a phenomenon never described previously. CONCLUSIONS: Strict law enforcement to prevent the contamination of edible oils is essential to avoid the occurrence of future similar outbreaks. PMID- 11198786 TI - Incidence of tuberculosis among patients receiving treatment with oral corticosteroids. AB - OBJECTIVES: To study the incidence and pattern of tuberculosis in patients taking systemic corticosteroids (CS). METHODS: Seventy seven patients taking oral CS for various respiratory diseases and eighty patients suffering from similar diseases but not receiving steroids were followed up for one year to study the incidence of tuberculosis. RESULTS: Five patients (6.5%) receiving CS developed tuberculosis as against none amongst the controls (p < 0.05). Of these, three patients had sputum positive pulmonary tuberculosis and one each had sputum negative pulmonary tuberculosis and tubercular meningitis. All patients were treated with standard anti-tubercular therapy; four patients improved whereas one died due to complications of disease. CONCLUSION: Systemic CS therapy causes a significant increase in incidence of tuberculosis. PMID- 11198787 TI - Composition of gallstones and sequential events in biliary lithogenesis--is it different in south India compared to north? AB - AIMS: This study was carried out to determine the gross type and composition of gallstones from South India in order to compare it with published results from the North to see whether the sequential events in biliary lithogenesis are different in these two geographical areas. MATHODOLOGY: A total of 76 stones collected from various hospitals in South India including JIPMER were analysed using X-ray crystallography. Patient characteristics were recorded. Gross typing was done according to Bockus' morphological criteria. RESULTS: Patients with gallstones in South India were found to be older in age with near equal gender distribution. Pigment calcium stones accounted for 56.5%, pigment stones for 17.2% and mixed stones for 14.2% of gallstones. Bilirubin and its salts were the most frequently identified class of compounds by crystallography. Analysis of gallstones layer by layer revealed equal distribution of bilirubin compounds between the centre and outer layers except crystalline bilirubin which was found only in outer layers. Vaterite, a polymorph of calcium carbonate was found in the nucleus, whereas vaterite and aragonite were found in the outer layers. Combination of anhydrous cholesterol and cholesterol II were found in the nucleus. Epitaxial relationship were found to hold good except for vaterite and aragonite. CONCLUSION: Gallstones from South India are probably due to infection rather than supersaturation as evidenced by predominance of pigment calcium stones and various types of bilirubin and calcium carbonate compounds. Vaterite is important for nucleation. Further growth of stones is influenced by epitaxial relationship. These findings are dissimilar to that reported from North India indicating a different stimulus for stone precipitation in these two areas. PMID- 11198788 TI - Intracystic tetracycline therapy for hypofunctioning cystic thyroid nodules. AB - OBJECTIVES: Hypofunctioning benign cystic thyroid nodules are a common occurrence in iodine deficient region. There are reports of resolution of recurrent thyroid cysts with tetracycline instillation. Hence we conducted a study in 20 patients with hypofunctioning benign cystic thyroid nodules to document response to intracystic instillation of tetracycline as a primary modality of treatment. METHODS: Twenty patients were thoroughly investigated for the presence of malignancy clinically, radiologically and cytologically. One milliliter of tetracycline was instilled under ultrasonographic guidance. Response to therapy was assessed clinically and ultrasonographically at one, three, six and 12 months. RESULTS: Study group comprised of five male and 15 female patients with mean age 30 +/- 8 years. Initial mean volume of nodules was 15 +/- 7 ml (6 to 27 ml), which was decreased to 3 +/- 3 ml at one month, 2 +/- 3 ml at three months, and 1 +/- 2 ml at six months. Maximum number of patients (75%) responded within three months, however two patients required reaspiration and reinstallation of tetracycline. Ultrasonography revealed fibrotic scar as thick wall with internal echodensities in six patients (30%) six month after sclerotherapy. There was high rate of patient satisfaction, as cosmetically tetracycline did not leave any scar, which was unavoidable with surgery. Six patients (30%) reported mild pain after injection, and one patient developed redness at the site of injection. CONCLUSIONS: Intracystic tetracycline sclerotherapy is highly effective as primary mode of treatment in hypofunctioning benign cystic thyroid nodule in selected group of patients not at high risk of malignancy. PMID- 11198789 TI - Lipid profile in smokers and tobacco chewers--a comparative study. AB - OBJECTIVE: The present study was undertaken to evaluate lipid profile in cigarette smokers and tobacco chewers and to see whether tobacco chewing causes same degree of alteration in lipid profile as done by smoking. METHODS: Serum lipid profile was studied in 30 smokers (Group A), 30 tobacco chewers (Group B) and 30 controls i.e., non-smokers and non-tobacco chewers (Group C). RESULTS: High density lipoprotein-cholesterol was lower both in smoker (P < 0.01) as well as in tobacco chewers (P < 0.001) than the controls. Both smokers and tobacco chewers had higher values of total cholesterol, low density lipoprotein cholesterol, very low density lipoprotein-cholesterol and, triglycerides as compared to non-smoker, non-tobacco chewer group whereas the differences in levels of lipids in smokers and tobacco chewers were not statistically significant. CONCLUSION: Though different mode of addictions, smoking and tobacco chewing have an equal and comparable adverse effects on lipid profile and therefore raising cardiovascular risk in same proportion. PMID- 11198790 TI - Variation of axillary temperature and its correlation with oral temperature. AB - Unilateral axillary temperature is recorded in unconscious patients and children due to its easy approach. OBJECTIVE: To evaluate variation of axillary temperature on the two sides and its correlation with oral temperature. SUBJECTS: One hundred and 46 healthy men and women, aged 12 through 52 years. METHODS: Axillary temperature from both sides and oral temperature were recorded using digital electronic thermometer in supine position with due precautions. RESULTS: Difference in temperature on the two sides of axilla was found to vary by as much as 0 degree F to 3.4 degrees F. Therefore, the data was grouped into higher and lower temperature ranges. The difference between mean oral and mean higher axillary temperature was found to be 0.5 degree F +/- 0.6 degree F (r = 0.564) while that in comparison to mean lower axillary temperature was 1.0 degree F +/- 0.89 degree F (r = 0.64). The difference between mean oral and mean axillary temperature was 1.0 degree F +/- 0.80 degree F (r = 0.84). CONCLUSIONS: Based on our observations, it is found that an average of temperature of both sides of axilla represents the axillary temperature more accurately and to get the correct oral equivalent of axillary temperature one should add 1 degree F to the mean axillary temperature. PMID- 11198792 TI - Evolving trends in the etiopathogenesis of acute renal failure. AB - Research during the last few years has uncovered the mechanisms responsible for acute renal failure. During the initiation phase of acute tubular necrosis sublethal injury, apoptosis or necrosis of the tubular epithelium, hemodynamic alterations, tubule obstruction and back leakage occur. Hypofiltration persists due to imbalance between endothelins and endothelium derived nitric oxide, medullary congestion and tubuloglomerular feedback. Recovery is characterised by tubular epithelium regeneration. A greater understanding of the pathogenesis of acute renal failure will allow better management of such cases. PMID- 11198791 TI - The foam mattress-back syndrome. AB - BACKGROUND: Many medical residents used to sleeping on cotton mattresses at home complain of mild to moderate back pain after sleeping on foam mattresses provided in the hospital and hostel rooms. OBJECTIVE: To determine the relationship of sleeping on foam mattress with the appearance of back pain in a 500 bedded multispecialty tertiary care hospital. METHODS: One hundred medical residents were interviewed for the appearance of backache after sleeping on 10 cm thick foam mattress provided to them in the hostels. Pain was scored over a visual analog scale of 10 cm. Effect of sleeping on a regular cotton mattress was assessed. RESULTS: Sixty-three (5 female residents) developed back pain on the morning of a night of sleep over the foam mattress. The pain was mostly of lower back and was not associated with any objective neurodeficit. Four residents on account of the backache reported thirteen episodes of absenteeism. Sixty-one residents had a relief of the pain on going home where they would sleep on regular cotton mattresses, only to recur after sleeping again on the foam mattress in the hospital/hostel. CONCLUSION: Sleeping on foam mattress is associated with the appearance of backache in medical residents which is reproducible and gets relieved after using regular cotton mattresses. PMID- 11198793 TI - Therapeutic angiogenesis. PMID- 11198794 TI - Face of God. PMID- 11198795 TI - Disseminated tuberculosis causing bilateral adrenal enlargement and Addison's disease. AB - The clinical features and computed tomography imaging of a patient with acute adrenal failure following disseminated tuberculosis is described. PMID- 11198796 TI - Heterophil negative infectious mononucleosis like syndrome due to hepatitis B virus. AB - A case of acute viral hepatitis B with features suggestive of infectious mononucleosis in a 20 year girl is described. A differential diagnosis of heterophil negative infectious mononucleosis like syndrome due to varied aetiology based on serology is emphasised. PMID- 11198797 TI - Histoplasmosis: an unusual presentation. AB - Histoplasma capsulatum (HC) infection is rare in India. We document a case of unilateral adrenal histoplasmosis in a 56 year male. The patient presented with hepatosplenomegaly, unilateral adrenal mass and significant weight loss. Since FNAC of adrenal mass was inconclusive, he underwent splenectomy, adrenalectomy and liver biopsy, histology of these specimens revealed HC only in adrenal mass. Subsequently, histoplasmin test was also performed which was also found to be positive. He responded well to parenteral amphotericin B and is under regular follow-up with no complaints now. PMID- 11198798 TI - Hydroxyurea induced leg ulcers. AB - A 34 years non diabetic lady with chronic myeloid leukaemia (CML) was treated with hydroxyurea and interferon. She developed leg ulcers. First time on left toe and three months later on right foot, a rare complication of hydroxyurea. Both were treated with local wound care and antibiotics. First time dose of hydroxyurea was reduced and second time drug was discontinued. PMID- 11198799 TI - Situs inversus and compressive myelopathy in Klippel Feil syndrome. PMID- 11198800 TI - Primary hypothyroidism presenting as vaginal bleeding in a five year old girl. PMID- 11198801 TI - Multiple myeloma presenting as malabsorption syndrome due to amyloidosis. PMID- 11198802 TI - Familial Pelger--Huet anomaly in a female with adenocarcinoma of colon in a cancer prone family. PMID- 11198803 TI - Effect of protein and phosphate restricted and calcium and alphacalcidol supplemented diet on renal and parathyroid functions and protein status in chronic renal failure patients. PMID- 11198804 TI - Bradyarrhythmia due to Rauwolfia in homeopathic doses. PMID- 11198805 TI - Paracetamol (acetaminophen) poisoning: report of two cases. PMID- 11198806 TI - Idiopathic hypoparathyroidism with extensive intracranial calcification associated with kinesogenic choreoathetosis. PMID- 11198807 TI - Relevance of timely multidrug antimalarial regime in falciparum malaria. PMID- 11198808 TI - Acute intermittent porphyria: a new cause of posterior leukoencephalopathy syndrome. PMID- 11198809 TI - Neurocysticercosis presenting as chronic meningitis. PMID- 11198810 TI - Angina--an Indian disease. PMID- 11198811 TI - Prognostic factors in severe and complicated malaria. PMID- 11198812 TI - Availability of thiazide diuretics in Chandigarh. PMID- 11198813 TI - Norfloxacin-induced hallucination--an unusual CNS toxicity of 4-fluoroquinolones. PMID- 11198814 TI - Medicine in the next millennium. PMID- 11198815 TI - Combinatorial biochemistry in plants: the case of O-methyltransferases. AB - Combinatorial chemistry is common place today in chemical synthesis. Virtually thousands of derivatives of a molecule can be achieved by automated systems. The use of biological systems to exploit combinatorial chemistry (combinatorial biochemistry) now has multiple examples in the polyketide field. The modular functional domain structure of polyketide synthases have been recombined through genetic engineering into unnatural constellations in heterologous hosts in order to produce polyketide structures not yet discovered in nature. We present herein an example for a potential type of combinatorial biochemistry in alkaloidal systems using various combinations of Thalictrum tuberosum (meadow rue) O methyltransferase subunits that result in heterodimeric enzymes with substrate specificities that differ from those of the homodimeric native enzymes. PMID- 11198816 TI - Cytotoxic labdane diterpenoids from Croton oblongifolius. AB - Three labdane diterpenoids, 2-acetoxy-3-hydroxy-labda-8(17),12(E)-14-triene, 3 acetoxy-2-hydroxy-labda-8(17),12(E)-14-triene, and 2,3-dihydroxy-labda 8(17),12(E),14-triene were isolated from stem bark of Croton oblongifolius. Their structures were established by spectroscopic data, and each was also tested for cytotoxicity against various human tumor cell lines. The latter compound showed non-specific, moderate, cytotoxicities against all the cell lines; whereas the first two compounds were less active. PMID- 11198817 TI - Phenylbutanoid dimers from the leaves of Alpinia flabellata. AB - Three phenylbutanoid dimers, cis- and trans-1-(2,4,5-trimethoxy-E-styryl)-2 (2,4,5-trimethoxy-Z-styryl)cyclobutane and 1,2-bis(2,4,5-trimethoxy-Z-styryl)- cyclobutane, were isolated from the leaves of Alpinia flabellata Ridley, together with three known compounds (2,4,5-trimethoxybenzaldehyde, 2,4,5 trimethoxycinnamaldehyde and 3,5-dihydroxy-7,4'-dimethoxyflavone). The structures of these compounds were determined by spectroscopic analysis. PMID- 11198818 TI - The chemical diversity and distribution of glucosinolates and isothiocyanates among plants. AB - Glucosinolates (beta-thioglucoside-N-hydroxysulfates), the precursors of isothiocyanates, are present in sixteen families of dicotyledonous angiosperms including a large number of edible species. At least 120 different glucosinolates have been identified in these plants, although closely related taxonomic groups typically contain only a small number of such compounds. Glucosinolates and/or their breakdown products have long been known for their fungicidal, bacteriocidal, nematocidal and allelopathic properties and have recently attracted intense research interest because of their cancer chemoprotective attributes. Numerous reviews have addressed the occurrence of glucosinolates in vegetables, primarily the family Brassicaceae (syn. Cruciferae; including Brassica spp and Raphanus spp). The major focus of much previous research has been on the negative aspects of these compounds because of the prevalence of certain "antinutritional" or goitrogenic glucosinolates in the protein-rich defatted meal from widely grown oilseed crops and in some domesticated vegetable crops. There is, however, an opposite and positive side of this picture represented by the therapeutic and prophylactic properties of other "nutritional" or "functional" glucosinolates. This review addresses the complex array of these biologically active and chemically diverse compounds many of which have been identified during the past three decades in other families. In addition to the Brassica vegetables, these glucosinolates have been found in hundreds of species, many of which are edible or could provide substantial quantities of glucosinolates for isolation, for biological evaluation, and potential application as chemoprotective or other dietary or pharmacological agents. PMID- 11198819 TI - Purification and characterization of a lectin from the mushroom Mycoleptodonoides aitchisonii. AB - A lectin was isolated from the mushroom Mycoleptodonoides aitchisonii by means of affinity chromatography on bovine submaxillary mucin (BSM)-Toyopearl and gel filtration on Superose 12 HR10/30 using a FPLC system. This lectin is composed of four identical 16 kDa subunits and the molecular mass of the intact lectin was estimated to be 64 kDa by gel filtration. In a hemagglutination inhibition assay, it exhibited strong sugar-binding specificity towards asialo-BSM among the mono- or oligo-saccharides and glycoproteins tested. The binding specificity of the lectin was also examined by surface plasmon resonance analysis. PMID- 11198820 TI - Tropane alkaloid production by shoot culture of Duboisia myoporoides R. Br. AB - This work demonstrates the presence of hyoscyamine and scopolamine at different stages of shoot regeneration from non-organogenic and organogenic calli. The 11 week-old non-organogenic calli contained 0.41+/-0.03 and 0.23+/-0.02 microg g(-1) dry wt hyoscyamine and scopolamine respectively. However, no root meristem was found in the calli. The alkaloids were absent in 2-week-old organogenic calli. The shoot-buds induced on the non-organogenic and organogenic calli did not contain these alkaloids. Hyoscyamine and scopolamine contents of the 6-week-old non-rooted shoots regenerated from non-organogenic calli were 7.8+/-0.1 and 6.5+/ 0.4 microg g(-1) dry wt respectively and those in the 9-week-old non-rooted shoot regenerated from organogenic calli were 38.5+/-0.4 and 3.6+/-0.1 microg g(-1) dry wt respectively. Hyoscyamine and scopolamine contents of the 4-week-old roots regenerated from non-organogenic and organogenic calli were higher than those in the non-rooted shoots. Since the presence of hyoscyamine and scopolamine in the non-rooted shoot depends on the stage of differentiation, manipulation of culture environment may improve hyoscyamine and scopolamine contents of the non-rooted shoots. PMID- 11198821 TI - Metabolism of gibberellins A1 and A3 in fruits and shoots of Prunus avium. AB - Isotope-labelled GA metabolites were identified by GC--MS, following HPLC fractionation of extracts derived from fruits or shoots, that had been incubated with [2H]- and [3H]- GA1 or [2H]- and [3H]- GA3. GA1 (1) was converted into GA8 (10) by developing fruits and vegetative shoots of sweet cherry (Prunus avium cv. 'Stella'), while GA3 (4) was converted into GA3-isolactone (17). Other metabolites of each GA were detected but were not identified unequivocally. These included a metabolite of GA1 (1) in fruitlets that was more polar (by reverse phase HPLC) than GA8 (10) and a metabolite of similar polarity to GA87 (6), was obtained after incubating fruitlets with GA3 (4). However, no evidence was obtained to suggest that GA87 (6) was a metabolite of GA3 (4) or that GA85 (2) was a metabolite of GA1 (1) in these tissues, under the conditions used. The pattern of metabolites obtained from vegetative tissues was similar to that from fruitlets. However, the results suggested that GA1 (1) and GA3 (4) were metabolised at a greater rate in shoots from mature trees than in shoots from seedlings, and that GA1 (1) was metabolised more rapidly than GA3 (4) in juvenile and mature shoots. We conclude from these observations that GA3 (4) is not a precursor of GA87 (6) and GA32 (5), also, that GA1 (1) is not a precursor of GA85 (2) and GA86 (3) in developing fruits or in vegetative shoots of sweet cherry. PMID- 11198822 TI - Profiling changes in metabolism of isoflavonoids and their conjugates in Lupinus albus treated with biotic elicitor. AB - Liquid chromatography with ultraviolet and mass spectrometric detection was applied to monitor changes in profiles of isoflavonoid glycosides and free isoflavonoid aglycones in Lupinus albus L. Four isoflavonoid aglycones, fourteen isoflavonoid glycosides, four flavonol glycosides and flavone glycoside were identified in lupin tissue after LC/ESI/MS analyses. An elicitor preparation from purified yeast cell wall was used to inject the shoots of 3-week old seedlings or to infiltrate the cut lupin leaves. Qualitative and quantitative changes of isoflavonoids were measured at different time points after elicitation. In elicited lupin seedlings increased amounts of prenylated isoflavone aglycones were identified. The concentrations of glycosidic conjugates of isoflavones present in plant tissue were less affected. PMID- 11198823 TI - A distinctive flavonoid chemistry for the anomalous genus Biebersteinia. AB - Leaf surface extracts of Biebersteinia orphanidis have yielded a complex mixture of five flavones with the unusual 5,7-dihydroxy-6,8-dimethoxy A ring substitution pattern. They are acerosin, hymenoxin, nevadensin, sudachitin and 5,7,4' trihydroxy-6,8-dimethoxyflavone. Also present at the leaf surface are gardenin B, luteolin, apigenin, acacetin and the coumarin umbelliferone. The internal leaf flavonoids include the 7-glucosides of apigenin, luteolin and tricetin, together with the 7-rutinosides of apigenin and luteolin. This profile differs from those of B. heterostemon and B. odora. It appears that B. orphanidis is as highly distinctive in its flavonoid pattern as it is phytogeographically. The data also confirm the conclusion of other studies, including rbcL and atpB gene sequence analysis, that Biebersteinia is completely unrelated to the Geraniaceae, where it was once placed. PMID- 11198824 TI - Bioactive oleanolic acid saponins and other constituents from the roots of Viguiera decurrens. AB - The bisdesmoside oleanolic acid saponin, 3-0-(methyl-beta-D glucuronopyranosiduronoate)-28-0-beta-D-glucopyranosyl-oleanolate along with nine known compounds (two diterpenic acids, one chromene, three triterpenes, one steroidal glycoside, and two monodesmoside oleanolic acid saponins), were obtained from Viguiera decurrens roots. The chemical structure of the bisdesmoside oleanolic saponin was determined by chemical and NMR spectral evidence. A mixture of monodesmoside saponins displayed cytotoxic activity against P388 and COLON cell lines (ED50= 2.3 and 3.6 microg/ml, respectively). Two of the known compounds showed insecticidal activity against the Mexican bean beetle larvae (Epilachna varivestis). PMID- 11198825 TI - Trianthenol: an antifungal tetraterpenoid from Trianthema portulacastrum (Aizoaceae). AB - An antifungal tetraterpenoid named trianthenol 1 has been isolated from the chloroform extract of Trianthema portulacastrum. Its structure was established as 15-hydroxymethyl-2,6,10,18,22,26,30-heptamethyl-14-methylene- 17-hentriacontene on the basis of spectroscopic data including high resolution mass and two dimensional NMR techniques. A benzaldehyde derivative 2, a pentacyclic triterpenoid 3 and benzoic acid derivatives 4-5 are also reported for the first time from Trianthema portulacastrum. PMID- 11198826 TI - Victory! PMID- 11198827 TI - Ultrasonographic screening for developmental dysplasia of the hip: an epidemiologic analysis (Part II). PMID- 11198828 TI - SLAP lesions: current concepts. AB - The presence and significance of superior glenoid labral tears have received increasing attention in the 1990s. The symptoms associated with labral tears can be quite disabling to competitive and recreational athletes alike. Recent basic science and clinical studies have contributed much to the understanding of these injuries, including their association with suprascapular nerve entrapment. This article reviews the current basic science and clinical understanding of SLAP (superior labrum anterior and posterior) lesions in order to guide clinicians and promote further investigation. PMID- 11198829 TI - Efficacy of single-dose and multidose rofecoxib in the treatment of post orthopedic surgery pain. AB - To determine the efficacy of rofecoxib in post-orthopedic surgery pain, we conducted a double-blind, randomized, placebo- and active-comparator-controlled, parallel-group trial. Two hundred eighteen patients enrolled. Day 1 patients received placebo, rofecoxib 50 mg, or naproxen sodium 550 mg. Days 2 through 5, the placebo and naproxen sodium groups received placebo, and the rofecoxib group received rofecoxib 25 or 50 mg. Rofecoxib 50 mg was superior to placebo (P < .05) and similar to naproxen sodium for all single-dose measures of pain relief. Days 2 through 5, the rofecoxib 50 mg group used less supplemental narcotic analgesia (P = .005) and reported less pain on global evaluations (P = .041) when compared with the placebo group; the efficacy of rofecoxib 25 mg fell between that of placebo and rofecoxib 50 mg for these endpoints (P < or = .267). Rofecoxib 50 mg once daily effectively treated post-orthopedic surgery pain. PMID- 11198830 TI - Back pain caused by benign tumors and tumor-like lesions of the thoracolumbar spine. AB - Twenty-two patients with benign tumors or tumor-like lesions of the spine (vertebral echinococcal cysts, eosinophilic granuloma) presented with back pain and deformity. The duration of pain ranged from 1 to 6 years. Five patients had incomplete paraplegia at admission. Spine deformity was observed in patients with osteoid osteoma, osteoblastoma, hemangioma, and vertebral echinococcal involvement. All patients underwent clinical evaluation, laboratory studies, and histologic studies. Electromyogram studies were performed in patients who had a neurologic deficit or nerve root irritation. Imaging evaluation consisted of plain films, bone scans, computed tomography scans, and magnetic resonance imaging scans. Fifteen patients had lumbar involvement; 7 had thoracic involvement. For 18 patients, management included tumor excision and thorough debridement of the lesion. Spinal instrumentation and fusion were used to correct the deformity and treat the instability in 5 patients. Patients were followed for 1 to 8 years. Of the 5 patients with incomplete paraplegia, 4 recovered completely, and the fifth (who had spinal cord hemangioma) improved 2 grades on Frankel's scale. The remaining patients were disease free and returned to routine daily activities. Benign tumors or tumor-like lesions of the thoracolumbar or lumbar spine are very rare and easily misdiagnosed in patients with persistent back pain. Patients whose symptoms progress or fail to respond over an appropriate period of time should be evaluated further. Complete excision of the tumor followed by spinal instrumentation in the presence of deformity or instability is the treatment of choice. PMID- 11198831 TI - Axial computed tomography of the pedicle in the lower cervical spine. AB - Using axial computed tomography (CT), we measured pedicle width, pedicle axis length, pedicle transverse angle, and distance between screw entry point and vertebrae midline in the cervical spines (C3-C7) of 40 patients. All measurements were greater in men than in women, and we noted significant sex differences at most levels of pedicle inner and outer widths (P < or = .05 or P < or = .01). Mean pedicle inner and outer widths for all levels and all patients ranged from 2.3 to 3.0 mm and from 5.0 to 6.0 mm, respectively. Mean distances between screw entry point and vertebrae midline ranged from 22.2 to 23.7 mm. Results of this study-along with axial CT measurements of individual pedicle diameter, pedicle transverse angle, and screw entry point-would be useful when considering and performing transpedicular screw fixation in the cervical spine. PMID- 11198832 TI - Two cases of osteochondroma recurrence after surgical resection. AB - Osteochondromas are the most common bone tumor found in children. A review of 114 resected osteochondromas over a 10-year period revealed recurrence in 2 cases. The overall recurrence rate of these lesions is less than 2% and was found to be 1.8% in this review. PMID- 11198833 TI - Intramedullary fixation of pediatric forearm diaphyseal fractures. AB - Surgical treatment of pediatric forearm fractures is controversial. In this retrospective study, we reviewed 24 skeletally immature radial and ulnar fractures in 24 patients treated with intramedullary Rush pins and/or Kirschner wires between 1994 and 1999. The indication for surgical intervention was unacceptable closed reduction, unstable fracture pattern, open fracture, or recurrence after nonsurgical treatment. For each patient, a sugar tong splint was used for 4 weeks, and pins were removed 8 weeks after surgery. Average length of follow-up was 32 months (range, 6-58 months). All fractures in this series healed. Average time to union was 8 weeks. There were no complications of delayed union, nonunion, infection, or neurovascular injury. All patients regained full range of motion of the injured extremity. PMID- 11198834 TI - Use of a reciprocating rasp as an adjunct to open acromioplasty. PMID- 11198835 TI - A 22-year-old woman with chronic, mild, intermittent knee pain. AB - The following case is presented to illustrate the roentgenographic and clinical findings of a condition of interest to orthopedic surgeons. The initial history, physical findings, and roentgenographic examination are found on the first page. The final clinical and roentgenographic diagnosis is presented on the following page. PMID- 11198836 TI - Esophageal cancer: a systematic review. AB - Carcinoma of the esophagus has one of the lowest possibilities of cure, with 5 year survival rates estimated to be approximately 10% overall; these rates are second only to hepatobiliary and pancreatic cancers. This fact and the rapid increase in the incidence of adenocarcinomas of the esophagus in recent years challenges us to identify areas of improvement for all aspects of this disease. We discuss potential reasons for the increase in the incidence of adenocarcinomas, evidence that defines the similarity between tumors of the gastroesophageal junction and the tubular esophagus, and other prognostic factors that may influence future modifications of our staging classification of this disease. Surgical advances have translated into improvements in surgical morbidity and mortality rates. Current therapeutic options and the relative merits of the options are discussed. Improvements in patient outcome most likely hinge on earlier diagnosis, more accurate staging, and the optimal use of combined modalities, coupled with technical advances in the modalities. A systematic review approach was undertaken to evaluate the performance characteristics of newer staging tools and the value of different combined modality approaches with particular focus on the use of those approaches for patients with potentially curable disease. A similar methodologic approach was used to address the utility of the many strategies currently used in practice for the palliation of esophageal tumors, with particular focus on the relief of malignant dysphagia. Finally, a summary of published guidelines and population based patterns of care are presented. This serves as an overview of how all of this evidence actually translates into the care we are providing. A coordinated international effort in population-based research and randomized controlled trials would be the cornerstone to future advances in this relatively uncommon but devastating disease. PMID- 11198837 TI - Benefits and outcomes of staff nurses' participation in decision making. AB - OBJECTIVES: To investigate the relations among staff nurses' participation in phases of the decision-making process related to decisions in nursing practice, competencies of nurse manager leadership, and nurse-physician collaboration. METHODS: This study is a secondary analysis of the Variations in Nursing Practice Model study. The data were derived from the responses of staff nurses to a questionnaire asking about their participation in decision making, their perception of the competency of nurse manager leadership, and their collaboration with physicians. RESULTS: Nurse-physician collaboration contributed to greater participation in all phases of both caregiving and condition-of-work decisions. The competency of nurse manager leadership had a small but significant positive correlation with participation in decision making, but it did not have a significant effect on phases of participation in both types of decisions. CONCLUSIONS: The study findings provide evidence to support the relations among an organizational structure, an organizational process, and a provider process of healthcare. Further research is needed to clarify the relation among structure, process, and specific outcomes. PMID- 11198838 TI - Building a strong nursing organization in a merged, service line structure. AB - In an increasingly complex healthcare environment, the discipline of nursing is difficult to define. Although a designated "department of nursing" may be absent on the organizational chart, the functional elements of the discipline remain. Nursing leaders will benefit from a framework to define and operationalize the core elements of nursing. The authors offer a five-phase methodology to enable the creation of a strong nursing organization in the face of mergers, service lines, and complex reporting structures. PMID- 11198839 TI - Nurse experience and education: effect on quality of care. AB - OBJECTIVE: To describe the relationships between the quality of patient care and the education and experience of the nurses providing that care. BACKGROUND: There is a call for more nurses with baccalaureate degrees and more experienced nurses to work in hospitals. Previous research studies have examined the characteristics, abilities, and work assignments of nurses with and without baccalaureate degrees but have not examined the quality of the patient care delivered. It is generally believed that more experienced nurses provide higher quality care, but again few studies have actually examined this issue. METHODS: A secondary analysis of data, collected in two previous studies of the relationship between nurse staffing (hours of care, staff mix) and the quality of patient care, was used to determine the relationship between nurses' education and experience and the quality of care provided. The data were collected at the patient care unit level (42 units in study 1 and 39 units in study 2). Quality of care was indicated by lower unit rates of medication errors and patient falls. RESULTS: Controlling for patient acuity, hours of nursing care, and staff mix, units with more experienced nurses had lower medication errors and lower patient fall rates. These adverse occurrence rates on units with more baccalaureate prepared nurses were not significantly better. PMID- 11198840 TI - Program logic. A planning and evaluation method. PMID- 11198841 TI - Nursing student residency program: a model for a seamless transition from nursing student to RN. AB - It takes a relatively long time for new nursing graduates to become oriented and comfortable with work routines on the nursing unit. To address the problem, the authors formed a partnership among three educational programs and three hospitals. This article describes a 900-hour residency program for senior baccalaureate nursing students to ease their transition into the role of beginning-level staff nurse in an acute-care setting. The benefits to the hospitals were decreased orientation time, less turnover in staff (50% at 2 years), and lower recruitment costs. PMID- 11198842 TI - E-learning: directions for nurses in executive practice. PMID- 11198843 TI - An expanded professional nursing role: increasing hospital reimbursement. PMID- 11198844 TI - Publicly available healthcare databases for administrative strategic planning. AB - Existing public databases may help nurse administrators better understand the rapidly changing and increasingly complex healthcare environment. The authors discuss the availability of public healthcare databases and demonstrate through a hypothetical query how nurse administrators can use these databases during their decision-making efforts. PMID- 11198845 TI - The structure-directing properties of [VOF5]2-. PMID- 11198846 TI - Syntheses of ketonated disulfide-bridged diruthenium complexes via C-H bond activation and C-S bond formation. AB - The alpha-C-H bonds of 3-methyl-2-butanone, 3-pentanone, and 2-methyl-3-pentanone were activated on the sulfur center of the disulfide-bridged ruthenium dinuclear complex [(RuCl(P(OCH3)3)2)2(mu-S2)(mu-Cl)2] (1) in the presence of AgX (X = PF6, SbF6) with concomitant formation of C-S bonds to give the corresponding ketonated complexes [(Ru(CH3CN)2(P(OCH3)3)2)(mu-SSCHR1COR2)(Ru(CH3CN)3(P(OCH3)3)2)]X3 ([5](PF6)3, R1 = H, R2 = CH(CH3)2, X = PF6; [6](PF6)3, R1 = CH3, R2 = CH2CH3, X = PF6; [7](SbF6)3, R1 = CH3, R2 = CH(CH3)2, X = SbF6). For unsymmetric ketones, the primary or the secondary carbon of the alpha-C-H bond, rather than the tertiary carbon, is preferentially bound to one of the two bridging sulfur atoms. The alpha-C-H bond of the cyclic ketone cyclohexanone was cleaved to give the complex [(Ru(CH3CN)2(P(OCH3)3)2)(mu-SS-1- cyclohexanon-2 yl)(Ru(CH3CN)3(P(OCH3)3)2)](SbF6)3 ([8](SbF6)3). And the reactions of acetophenone and p-methoxyacetophenone, respectively, with the chloride-free complex [(Ru(CH3CN)3(P(OCH3)3)2)2(mu-S2)]4+ (3) gave [(Ru(CH3CN)2(P(OCH3)3)2)(mu SSCH2COAr)(Ru(CH3CN)3(P(OCH3)3)2)](CF3SO3)3 ([9](CF3SO3)3, Ar = Ph; [10](CF3SO3)3, Ar = p-CH3OC6H4). The relative reactivities of a primary and a secondary C-H bond were clearly observed in the reaction of butanone with complex 3, which gave a mixture of two complexes, i.e., [(Ru(CH3CN)2(P(OCH3)3)20(mu SSCH2COCH2CH3)(Ru(CH3CN)3(P(OCH3)3)2)](CF3SO3)3 ([11](CF3SO3)3) and [(Ru(CH3CN)2(P(OCH3)3)2)(mu-SSCHCH3COCH3)(Ru(CH3CN)3(P(OCH3)2)](CF3SO3)3 ([12](CF3SO3)3), in a molar ratio of 1:1.8. Complex 12 was converted to 11 at room temperature if the reaction time was prolonged. The relative reactivities of the alpha-C-H bonds of the ketones were deduced to be in the order 2 degrees > 1 degree > 3 degrees, on the basis of the consideration of contributions from both electronic and steric effects. Additionally, the C-S bonds in the ketonated complexes were found to be cleaved easily by protonation at room temperature. The mechanism for the formation of the ketonated disulfide-bridged ruthenium dinuclear complexes is as follows: initial coordination of the oxygen atom of the carbonyl group to the ruthenium center, followed by addition of an alpha-C-H bond to the disulfide bridging ligand, having S=S double-bond character, to form a C-S S-H moiety, and finally completion of the reaction by deprotonation of the S-H bond. PMID- 11198847 TI - Unsaturated Ru(0) species with a constrained bis-phosphine ligand: [Ru(CO)2(tBu2PCH2CH2PtBu2)]2. Comparison to [Ru(CO)2(PtBu2Me)2]. AB - The synthesis of Ru(C2H4)(CO)2(dtbpe) (dtbpe = tBu2PC2H4PtBu2), then green [Ru(CO)2(dtbpe)]n is described. In solution, n = 1, while in the solid state, n = 2; the dimer has two carbonyl bridges. DFTPW91, MP2, and CCSD(T) calculations show that the potential energy surface for bending one carbonyl out of the RuP2C(O) plane is essentially flat. Ru(CO)2(dtbpe) reacts rapidly in benzene solution to oxidatively add the H-E bond of H2, HCl, HCCR (R = H, Ph), [HOEt2]BF4, and HSiEt3. The H-C bond of C6HF5 oxidatively adds at 80 degrees C. CO adds, as does the C=C bond of H2C=CHX (X = H, F, Me). The following do not add: N2, THF, acetone, H3COH, and H2O. PMID- 11198848 TI - Preparation of polyetherol-appended sulfur porphyrazines and investigations of peripheral metal ion binding in polar solvents. AB - We describe the complete synthesis and characterization of a new family of peripherally functionalized porphyrazines (pz's) with four, three, or two (in a trans conformation) bis[thioethoxy(ethoxy)ethanol] moieties appended at the pyrroles. These "polyetherol" groups serve as weak exocyclic binding sites for a number of metal ions and also provide solubility of the pz's in low molecular weight alcohols and water. Electronic spectra of the modified porphyrazines exhibit distinct changes in the visible region (both absorbance and fluorescence) in response to treatment with Ag+, Pb2+, Cd2+, Cs+, and Ni2+ in solution. Such properties make these compounds intriguing candidates for incorporation into the transducer layers in optically based chemical sensors. PMID- 11198849 TI - Vanadium(IV) and -(V) complexes with O,N-chelating aminophenolate and pyridylalkoxide ligands. AB - Two different monoanionic O,N-chelating ligand systems, i.e., [OC6H2(CH2NMe2)-2 Me2-4,6]- (1) and [OCMe2([2]-Py)]- (2), have been applied in the synthesis of vanadium(V) complexes. The tertiary amine functionality in 1 caused reduction of the vanadium nucleus to the 4+ oxidation state with either [VOCl3], [V(=NR)Cl3], or [V(=NR)(NEt2)3] (R = Ph, (3a, 5a), R = p-Tol (3b, 5b)), and applying 1 as a reducing agent resulted in the synthesis of the vanadium(IV) complexes [VO(OC6H2(CH2NMe2)-2-Me2-4,6)2] (4) and [V(=NPh)(OC6H2(CH2NMe2)-2-Me2-4,6)2] (6). In the case of [V(=N-p-Tol)(NEt2)(OC6H2(CH2NMe2)-2-Me2-4,6)2] (7b), the reduction was sufficiently slow to allow its characterization by 1H NMR and variable temperature studies showed it to be a five-coordinate species in solution. Although the reaction of 1 with [V(=N-p-Tol)(O-i-Pr)3] (9b) did not result in reduction of the vanadium nucleus, vanadium(V) compounds could not be isolated. Mixtures of the vanadium(V) (mono)phenolate, [V(=N-p-Tol)(O-i-Pr)2(OC6H2(CH2NMe2) 2-Me2-4,6)] (10), and the vanadium(V) (bis)phenolate, [V(=N-p-Tol)(O-i Pr)(OC6H2(CH2NMe2)-2-Me2-4,6)2] (11), were obtained. With the pyridylalkoxide 2, no reduction was observed and the vanadium(V) compounds [VOCl2(OCMe2([2]-Py))] (12) and [V(=N-p-Tol)Cl2(OCMe2([2]-Py)] (13) were obtained. 51V NMR showed 7b and 12 to be five-coordinate in solution, whereas for 10, 11, and 13 a coordination number of 6 was found. Compounds 12 and 13 showed decreased activity compared to their nonchelated vanadium(V) analogues when applied as catalysts in ethene polymerization. Two polymorphic forms with a difference in the V-N-C angle of 12.5 degrees have been found for 6. Crystal data: 6.Et2O, triclinic, P1, a = 11.1557(6) A, b = 12.5744(12) A, c = 13.1051(14) A, alpha = 64.244(8) degrees, beta = 70.472(7) degrees, gamma = 87.950(6) degrees, V = 1547(3) A3, Z = 2; 6.C6H6, triclinic, P1, a = 8.6034(3) A, b = 13.3614(4) A, c = 15.1044(5) A, alpha = 98.182(3) degrees, beta = 105.618(2) degrees, gamma = 107.130(2) degrees, V = 1551.00(10) A3, Z = 2; 12, orthorhombic, Pbca, a = 11.8576(12) A, b = 12.6710(13) A, c = 14.722(2) A, V = 2211.9(4) A3, Z = 8. PMID- 11198850 TI - An integrated approach to the mid-spin state (S = 3/2) in six-coordinate iron(III) chiroporphyrins. AB - An intermediate-spin state very close to the mid-spin state (S = 3/2) can be stabilized in a ferric porphyrin by an integrated approach which combines the favorable effects of a weak axial field strength and of a small macrocycle hole. Axial ligand exchange by reaction of chloroiron(III)tetramethylchiroporphyrin [(TMCP)FeCl] with silver perchlorate in ethanol-chloroform leads to ethanol ligated ferric chiroporphyrins. Two distinct crystalline products containing a bisethanol complex [[(TMCP)FeIII(EtOH)2]ClO4] and three variants of a mixed ethanol-water complex [[(TMCP)FeIII(EtOH)(H2O)]ClO4] have been structurally characterized in the solid state. The small hole of the ruffled chiroporphyrin and the weak axial oxygen ligation result in strongly tetragonally distorted complexes. The six-coordinate species exhibit long axial Fe-O bond distances (2.173(5)-2.272(4) A) and the shortest equatorial Fe-N(av) distances (1.950(5) 1.978(7) A) found as yet in a ferric porphyrin, reflecting a singly occupied dz2 orbital and a largely depopulated dx2-y2 orbital. An intriguing case of bond stretch isomerism is seen for the axial Fe-O bonds in two crystallographically independent mixed ethanol-water species, and it is accounted for by their distinct intra- and intermolecular hydrogen-bond arrays. The Mossbauer spectrum (delta = 0.35(1) mm s-1 and delta EQ = 3.79(1) mm s-1 at 77 K) indicates a strong tetragonal distortion around the ferric ion, in agreement with the structural data. The value of the magnetic moment (mu eff = 3.8 mu B in the range 50-300 K) strongly supports a mid-spin state (S = 3/2). The EPR spectrum at 80 K (g perpendicular approximately 4.0, g parallel approximately 2.00) is consistent with a nearly pure mid-spin state (4A2) with little rhombic distortion. The 1H NMR spectra in CDCl3-EtOH exhibit upfield-shifted resonances for the pyrrole protons (delta approximately -30 ppm) which are consistent with the depopulated iron dx2-y2 orbital. Solution equilibria with water and various alcohols, and the spin state of the corresponding species, are discussed on the basis of the NMR data. The bisethanol and ethanol-water species are potential models of unknown hemoprotein ligation states such as Tyr(OH)/Tyr(OH) or Tyr(OH)/H2O that could be obtained by site-directed mutagenesis. PMID- 11198851 TI - Syntheses of novel exo and endo isomers of ansa-substituted fluorophosphazenes and their facile transformations into spiro isomers in the presence of fluoride ions. AB - Reactions of the dilithiated diols RCH2P(S)(CH2OLi)2 [R = Fc (1), Ph (2) (Fc = ferrocenyl)] with N3P3F6 in equimolar ratios at -80 degrees C result exclusively in the formation of two structural isomers of ansa-substituted compounds, endo RCH2P(S)(CH2O)2[P(F)N]2(F2PN) [R = Fc (3a), Ph (4a)] and exo RCH2P(S)(CH2O)2[P(F)N]2(F2PN) [R = Fc (3b), Ph (4b)], which are separated by column chromatography. Increasing the reaction temperature to -40 degrees C results in more of the exo isomers 3b and 4b at the expense of the endo isomers. The formation of the ansa-substituted compounds is found to depend on the dilithiation of the diols, as a reaction of the silylated phosphine sulfide FcCH2P(S)(CH2OSiMe3)2 (5) with N3P3F6 in the presence of CsF does not yield either 3a or 3b but instead gives the spiro isomer [FcCH2P(S)(CH2O)2 PN](F2PN)2 (6) as the disubstitution product of N3P3F6. The ansa isomers 3a and 3b are transformed into the spiro compound 6 in the presence of catalytic amounts of CsF at room temperature in THF, while 4a and 4b are transformed into the spiro compound [PhCH2P(S)(CH2O)2PN](F2PN)2 (7) under similar conditions. The novel conversions of ansa-substituted phosphazenes into spirocyclic phosphazenes were monitored by time-dependent 31P NMR spectroscopy. The effect of temperature on a transformation was studied by carrying out reactions at various temperatures in the range from -60 to +33 degrees C for 3b. In addition, compounds 3a, 3b, 4a, and 6 were structurally characterized. In the case of the ansa compounds, the nitrogen atom flanked by the bridging phosphorus sites was found to deviate significantly from the plane defined by the five remaining atoms of the phosphazene ring. PMID- 11198852 TI - Application of n-Bu4NHF2 as a fluorinating agent for the preparation of fluoroanions: synthesis and crystal structure of the anions [t-BuPO3AlF2]2(2-), [PhPO3AlF2]2(2-), and [(O-i-Pr)3Ti(mu-F)2(mu-O-i-Pr)Ti(O-i-Pr)3]-. AB - The first phosphonate anions of aluminum-containing fluorine and an anionic bridged fluoroalkoxy derivative of titanium have been realized using n-Bu4NHF2 as a fluorinating agent in organometallic synthesis. Reactions of [RPO3AlMe]4 [R = Ph (1), t-Bu] with n-Bu4NHF2 yield organic-soluble compounds of the type [n Bu4N]2[RPO3AlF2]2 [R = Ph (2), t-Bu (3)], whereas the reaction of Ti(O-i-Pr)4 with n-Bu4NHF2 results in the formation of [n-Bu4N][O-i-Pr)3Ti(mu-F)2(mu-O-i Pr)Ti(O-i-Pr)3] (4). These compounds have been obtained in high yields and have been adequately characterized through spectroscopic techniques and X-ray diffraction studies. PMID- 11198853 TI - TAS+(Z)-Me3CNSN- and TAS+(E)-Me3SiNSN-: does the anion-cation interaction influence the configuration? AB - TAS+ salts (TAS = (Me2N)3S) of the sulfur diimide anions Me3XNSN- (X = C (1a), Si (1b)) were prepared by Si-N bond cleavage from the corresponding sulfur diimides Me3XNSNSiMe3 and TAS-fluoride ((Me2N)3S+Me3SiF2-) and characterized by X-ray crystallography and multinuclear NMR spectroscopy. According to the experimentally determined bond lengths and theoretical calculations, the Me3XNSN- anions are best described as thiazylamides Me3X-N-S identical to N rather than sulfur diimides Me3X-N=S=N. In agreement with the calculated and experimentally determined structures of the isoelectronic thionylimides RNSO, 1a adopts the Z configuration, which is electronically favored due to anomeric effects. The electronically disfavored E-configuration of 1b in the solid state can be explained by weak anion-cation interaction. PMID- 11198854 TI - Steric effects control the structure of the solvated lanthanum(III) ion in aqueous, dimethyl sulfoxide, and N,N'-dimethylpropyleneurea solution. An EXAFS and large-angle X-ray scattering study. AB - The structure of the solvated lanthanum(III) ion has been determined in aqueous, dimethyl sulfoxide, and N,N'-dimethylpropyleneurea solution by means of the EXAFS and large-angle X-ray scattering (LAXS) techniques. The close agreement between the EXAFS spectra of solid nonaaqualanthanum(III) trifluoromethanesulfonate and of an aqueous lanthanum(III) perchlorate solution shows that the hydrated lanthanum(III) ion in aqueous solution most probably has the same structure as in the solid, i.e., nine water molecules coordinated in a tricapped trigonal prismatic configuration. The data analysis from EXAFS and LAXS measurements of the aqueous solution resulted in the La-O bond distances 2.52(2) and 2.65(3) A to the water molecules in the prism and the capping positions, respectively. The LAXS study shows a second hydration sphere consistent with approximately 18 water molecules at 4.63(2) A. The EXAFS spectra of solid octakis(dimethyl sulfoxide)lanthanum(III) trifluoromethanesulfonate and a dimethyl sulfoxide solution of this salt are also similar. The data analysis of EXAFS and LAXS measurements assuming eight-coordination around lanthanum yielded an La-O bond distance of 2.50(2) A, and an La...S distance of 3.70(3) A, giving an La-O-S angle of 133(2) degrees. The EXAFS data of an N,N'-dimethylpropyleneurea solution of lanthanum(III) trifluoromethanesulfonate gave the La-O bond distance 2.438(4) A and the La...C distance 3.41(2) A, which correspond to an La-O-C angle of 131(2) degrees. The La-O bond distance is consistent with seven-coordination around lanthanum, on the basis of the variation of the ionic radii of the lanthanum(III) ion with different coordination numbers. PMID- 11198855 TI - Solvation of the bismuth(III) ion by water, dimethyl sulfoxide, N,N' dimethylpropyleneurea, and N,N-dimethylthioformamide. An EXAFS, large-angle X-ray scattering, and crystallographic structural study. AB - The structure of the solvated bismuth(III) ion in aqueous, dimethyl sulfoxide, N,N'-dimethylpropyleneurea, and N,N-dimethylthioformamide solution has been studied by means of EXAFS and large-angle X-ray scattering (LAXS). The crystal structures of the solid compounds octakis(dimethyl sulfoxide)bismuth(III) perchlorate, [Bi(OS(CH3)2)8](ClO4)3, hexakis(N,N' dimethylpropyleneurea)bismuth(III) perchlorate, [Bi(OCN2(CH2)3(CH3)2)6](ClO4)3, and nonaaquabismuth(III) trifluoromethanesulfonate, [Bi(H2O)9](CF3SO3)3 (redetermination), have been determined. The aqueous solutions must be strongly acidic, since the hydrated bismuth(III) ion starts to hydrolyze into Bi6O4(OH)4(6+) complexes already at an excess of strong acid at 1.0 mol.dm-3. For very acidic aqueous perchlorate solutions, the LAXS and EXAFS data gave a satisfactory fit for eight-coordination of the bismuth(III) ion, with a mean Bi-O bond distance of 2.41(1) A. The crystal structure of octakis(dimethyl sulfoxide)bismuth(III) perchlorate shows that the bismuth(III) ion coordinates eight dimethyl sulfoxide molecules via the oxygen atoms in a distorted square antiprismatic configuration. The mean Bi-O bond distance is 2.43 A and the mean Bi...S distance 3.56 A. For the dimethyl sulfoxide solution, the corresponding mean distances were found to be 2.411(6) and 3.535(12) A. The N,N' dimethylpropyleneurea-solvated bismuth(III) ion is octahedrally coordinated in both solid state and solution with the Bi-O bond distances of 2.324(5) and 2.322(3) A, respectively. The bismuth(III) ion is six-coordinated in the sulfur donor solvent N,N-dimethylthioformamide with a mean Bi-S bond distance of 2.794(8) A. A comparison with the structure of the solvated lanthanum(III) ion shows that the bismuth(III) ion is smaller for all coordination numbers. New effective ionic radii for the bismuth(III) ion in different coordination numbers are proposed, based on results in this study and in the literature. PMID- 11198856 TI - Luminescent Langmuir-Blodgett films of platinum(II) complex [Pt(L18)Cl](PF6) (L18 = 2,6-bis(1-octadecylbenzimidazol-2-yl)pyridine). AB - A novel amphiphilic Pt complex containing 2,6-bis(1-octadecylbenzimidazol-2 yl)pyridine (L18), [Pt(L18)Cl](PF6), has been synthesized. The complex exhibits concentration-dependent absorption and emission spectra in solution. With increasing the concentration of the Pt complex, we observed a new absorption band centered at 550 nm derived from a metal-metal d sigma* to ligand pi* charge transfer (MMLCT) transition and the corresponding broad emission centered at 650 nm. The Pt complex is surface-active, and the surface pressure-area isotherm reveals three phase transitions. The three phases correspond to one liquid expanding phase and two solid-condensed phases, respectively, with different intermolecular overlap in the "flat-on" orientation at the air-water interface. Without additives such as fatty acids, the complex forms a stable and reproducible Langmuir-Blodgett (LB) multilayer film above a surface pressure of 15 mN m-1. Strong emission from the LB films, even monolayer, was observed. Comparing the relative emission intensity of the MMLCT band for transferred LB monolayer film with that for cast films, we concluded that Pt-Pt interactions are suppressed in the LB film. Instead, the emission at 600 nm arising from the ligand-ligand pi-pi interacted excited state became dominant. The results would provide the insight into the control of molecular ordering for planar Pt complexes from the viewpoint of characteristic excited states. PMID- 11198857 TI - M(mu-CN)Fe(mu-CN)M' chains with phthalocyanine iron centers: preparation, structures, and isomerization. AB - The molecular building blocks Fe(II)Pc (Pc = phthalocyaninato2-), Fe(III)Pc, ZnPc, Cp(dppe)Fe, and Cp(PPh3)2Ru were combined in the cyanide-bridged dinuclear reference compounds with M-CN-ZnPc and M-CN-FePc-CN arrays containing Fe(II)Pc and Fe(III)Pc. The linear trinuclear species with the M(mu-CN)Fe(mu-CN)M' backbone were prepared for both Fe(II)Pc and Fe(III)Pc centers, for terminal Fe/Fe, Fe/Ru, and Ru/Ru combinations and for all three possible cyanide orientations (M-CN-Fe-NC-M', M-CN-Fe-CN-M', and M-NC-Fe-CN-M'). The 15 complexes obtained were identified from their IR spectra and six structure determinations. The preferred orientation of the cyanide bridges could be established starting from the [Fe-NC-Fe(III)Pc-CN-Fe]+ complex, which is labile in solution and isomerizes to the corresponding [Fe-CN-Fe(III)Pc-NC-Fe]+ complex. A kinetic analysis of this isomerization has yielded an activation barrier of roughly 110 kJ/mol. PMID- 11198858 TI - M(mu-CN)Fe(mu-CN)M' chains with phthalocyanine iron centers: redox, spin-state, and mixed-valence properties. AB - Dinuclear complexes with M-CN-ZnPc and M-CN-FePc-CN arrays and trinuclear complexes with M(mu-CN)Fe(mu-CN)M' arrays containing central metal phthalocyaninato (Pc) and external Cp(dppe)Fe or Cp(PPh3)2Ru building blocks (M) and having all possible orientations of the bridging cyanide ligands were subjected to electrochemical and preparative redox reactions. The species with unpaired electrons show characteristic MMCT bands in the near-IR spectra, the energies of which depend in a typical fashion on the nature of the building blocks and the orientation of the cyanide bridges and can be correlated with the redox potentials. Cyclic voltammetry has revealed electronic communication between the external organometallic units. An analysis of the MMCT spectra allows the assignment of the odd-electron complexes as class II mixed-valence species. The magnetic moments of the complexes with central Fe(III)Pc units are characteristically higher than the spin-only value for one unpaired electron. A Mossbauer investigation has shown that the M-CN-Fe(III)Pc-NC-M complexes undergo a low-spin-to-high-spin crossover of the Fe(III) component above room temperature. PMID- 11198859 TI - Manganese citrate chemistry: syntheses, spectroscopic studies, and structural characterizations of novel mononuclear, water-soluble manganese citrate complexes. AB - The first two mononuclear manganese citrate complexes, (NH4)4[MnII(C6H5O7)2] (1) and (NH4)5[MnIII(C6H4O7)2].2H2O (2) were synthesized in aqueous solutions near physiological pH values. They were isolated in their pure crystalline forms and characterized by elemental analyses and spectroscopic techniques, including UV/visible, electron paramagnetic resonance, Fourier transformed infrared, and magnetic susceptibility measurements. Compound 1 crystallizes in the monoclinic space group P2(1)/c, with a = 8.777(1) A, b = 13.656(3) A, c = 9.162(2) A, beta = 113.62(2) degrees, V = 1006.2(6) A3, and Z = 2. Compound 2 crystallizes in the triclinic space group P1, with a = 9.606(3) A, b = 9.914(3) A, c = 7.247(3) A, alpha = 91.05(1) degrees, beta = 105.60(1) degrees, gamma = 119.16(1) degrees, V = 571.3(3) A3, and Z = 1. The X-ray crystal structures of 1 and 2 revealed that, in both cases, the manganese ion is six-coordinate and is bound by two citrate ligands in a distorted octahedral fashion. In the case of complex 1, the citrate ion binds to Mn2+ as a triply deprotonated ligand, retaining the central carbon hydroxyl hydrogen, whereas, in the case of compound 2, the citrate ligand coordinates to Mn3+ as a fully deprotonated entity. Compound 2 contains water molecules of crystallization in the unit cell which, through extensive hydrogen bonding interactions, bestow considerable stability upon the Mn(3+)-citrate assembly. There are significant contributions to the stabilities of the assembled lattices in 1 and 2 arising from the ammonium counterions neutralizing the high anionic charges of the complexes. The EPR spectra attest to the presence of paramagnetic Mn2+ and Mn3+ species in the solid state. Corroborative evidence is obtained from the magnetic susceptibility measurements in the range 5-300 K. Complexes 1 and 2 present clear cases of mononuclear manganese citrate species relevant to manganese speciation in biological media and potentially related to the beneficial as well as toxic effects of manganese on humans. PMID- 11198860 TI - Metal vs ligand reduction in complexes of 1,3-dimethylalloxazine (DMA) with copper(I), ruthenium(II), and tungsten(VI). Crystal structures of (DMA)WO2Cl2 and (bis(1-methylimidazol-2-yl)ketone)WO2Cl2. AB - The complexes [(DMA)Cu(PPh3)2](BF4) (1) (DMA = 1,3-dimethylalloxazine), [(DMA)Ru(bpy)2](PF6)2 (2), and (DMA)WO2Cl2 (3) were obtained as O4-N5-chelated species, as evident from an X-ray crystal structure analysis for 3 and from spectroscopy (NMR, IR, and UV-vis spectroelectrochemistry) for 1 and 2. The tungsten(VI) center in 3 has its oxide ligands in a cis/equatorial position and the chloride ligands in a trans/axial position; it also exhibits a relatively short bond to O4 (2.232(3) A) and a very long bond to N5 (2.462(3) A). Comparison with the new structurally characterized compound (BIK)WO2Cl2 (4) (BIK = bis(1 methylimidazol-2-yl)ketone), which has W-N bonds of about 2.30 A, confirms the unusual length of the W-N bond in 3, probably caused by repulsion between one of the oxo ligands and the peri-hydrogen atom (H6) of DMA. One-electron reduction of the complexes occurs reversibly at room temperature in THF (1, 2) or at 198 K in CH2Cl2 (3). EPR spectroscopy reveals that this process is ligand-centered for 1 and 2 but metal-centered for 3. Density functional methods and ab initio methodology are used to illustrate the correspondence in spin distribution between the radical anion pi systems of alloxazine and isoalloxazine ("flavosemiquinone"). PMID- 11198861 TI - Ligand macrocycle structural effects on copper-dioxygen reactivity. AB - With the goal of understanding how the nature of the tridentate macrocyclic supporting ligand influences the relative stability of isomeric mu-eta 2:eta 2 peroxo- and bis(mu-oxo)dicopper complexes, a comparative study was undertaken of the O2 reactivity of Cu(I) compounds supported by the 10- and 12-membered macrocycles, 1,4,7-R3-1,4,7-triazacyclodecane (R3TACD; R = Me, Bn, iPr) and 1,5,9 triisopropyl-1,5,9-triazacyclododecane (iPr3TACDD). While the 3-coordinate complex [(iPr3TACDD)Cu]SbF6 was unreactive with O2, oxygenation of [(R3TACD)Cu(CH3CN)]X (R = Me or Bn; X = ClO4- or SbF6-) at -80 degrees C yielded bis(mu-oxo) species [(R3TACD)2Cu2(mu O)2]X2 as revealed by UV-vis and resonance Raman spectroscopy. Interestingly, unlike the previously reported system supported by 1,4,7-triisopropyl-1,4,7-triazacyclononane (iPr3TACN), which yielded interconverting mixtures of peroxo and bis(mu-oxo) compounds (Cahoy, J.; Holland, P. L.; Tolman, W. B. Inorg. Chem. 1999, 38, 2161), low-temperature oxygenation of [(iPr3TACD)Cu(CH3CN)]SbF6 in a variety of solvents cleanly yielded a mu-eta 2:eta 2-peroxo product, with no trace of the bis(mu-oxo) isomer. The peroxo complex was characterized by UV-vis and resonance Raman spectroscopy, as well as an X-ray crystal structure (albeit of marginal quality due to disorder problems). Intramolecular attack at the alpha C-H bonds of the substituents was indicated as the primary decomposition pathway of the oxygenated compounds through examination of the decay kinetics and the reaction products, which included bis(mu-hydroxo)- and mu-carbonato-dicopper complexes that were characterized by X-ray diffraction. A rationale for the varying results of the oxygenation reactions was provided by analysis of (a) the X-ray crystal structures and electrochemical behavior of the Cu(I) precursors and (b) the results of theoretical calculations of the complete oxygenated complexes, including all ligand atoms, using combined quantum chemical/molecular mechanics (integrated molecular orbital molecular mechanics, IMOMM) methods. The size of the ligand substituents was shown to be a key factor in controlling the relative stabilities of the peroxo and bis(mu-oxo) forms, and the nature of this influence was shown by both theory and experiment to depend on the ligand macrocycle ring size. PMID- 11198862 TI - Tuning the rotational behavior of lopsided heterocyclic nitrogen ligands (L) in octahedral cis-[Ru(bpy)2(L)2](PF6)2 complexes. A variable-temperature 1H NMR study. AB - In this paper are presented the syntheses, characterizations, and dynamic solution behaviors of three cis-[Ru(bpy)2(L)2] (bpy = 2,2'-bipyridine) complexes, 1-3, in which L represents the monodentate ligands 1-methylimidazole (MeIm), 1,2 dimethylimidazole (Me2Im), and 1-methylbenzimidazole (MeBim), respectively. Because of their different steric properties, these three monodentate ligands yield complexes that show quite different fluxional behaviors in solution. These behaviors are studied with several 1H NMR techniques at various temperatures between -95 and degrees C. The 1H NMR spectra of 1, which has the smallest monodentate ligand of the three used, indicate the complex to be in fast exchange (i.e., the imidazoles rotate around their Ru-N axes) at all recording temperatures. The sterically more demanding ligands, Me2Im and MeBim, in 2 and 3, respectively, are in fast exchange at 55 degrees C and in slow exchange at low temperatures, showing three different atropisomers: two head-to-tail (HT) isomers and one head-to-head (HH) isomer. The newly synthesized bidentate ligand 1,2-bis (1-methyl-2-benzimidazolyl)ethane (mdbz) forms the complex cis [Ru(bpy)2(mdbz)](PF6)2 (4), in which the two benzimidazole moieties are constrained and relatively fixed. The two tethered benzimidazoles in 4 cannot rotate around their Ru-N axes, and therefore 4 is a good model for the main HT isomer of 3. PMID- 11198863 TI - Aminotroponiminates as ligands for potential metal-based nitric oxide sensors. AB - A family of new fluorescently labeled ligands, HRDATI, was prepared to develop transition-metal-based NO sensing strategies. The ligands are composed of aminotroponiminates (ATIs) with a dansyl fluorophore on one of the imine nitrogen atoms and an alkyl substituent, either i-Pr (8), t-Bu (9), or Bz (10), on the other. Bis(chelate) Co2+ ([Co(i-PrDATI)2] (12), [Co(t-BuDATI)2] (14), [Co(BzDATI)2] (15)) and Zn2+ ([Zn(i-PrDATI)2] (13)) complexes were prepared and characterized by X-ray crystallography. The bis(ATI) complex [Co(i-Pr2ATI)2] (11) was also prepared and its X-ray crystal structure determined. Cyclic voltammetry reveals reversible redox waves at -2.57 and -0.045 V (vs Cp2Fe/Cp2Fe+) in THF for the Co2+/Co+ and Co3+/Co2+ couples, respectively, of 11. Only a Co2+/Co+ wave at 2.09 V is observed for 12. When excited at 350 nm, the HRDATI ligands and the diamagnetic Zn2+ complex 13 fluoresce around 500 nm, whereas the paramagnetic Co2+ complexes quench the fluorescence. These air-stable cobalt compounds react with nitric oxide to dissociate a DATI ligand and form neutral dinitrosyl complexes, [Co(NO)2(RDATI)]. The release of the fluorophore-containing ligand is accompanied by an increase in fluorescence intensity, thus providing a strategy for fluorescent NO sensing. Linking two DATI moieties via a tetramethylene chain affords the ligand H2DATI-4 (18). The Co2+ complex [Co(DATI-4)] (19) reacts more readily with NO than the bis(DATI) compounds and also displays an increase in fluorescence intensity upon NO binding. PMID- 11198864 TI - Trithiacyclononane as a ligand for potential technetium and rhenium radiopharmaceuticals: synthesis of [M(9S3)(SC2H4SC2H4S)][BF4] (M = 99Tc, Re, 188Re) via C-S bond cleavage. AB - Chemical or electrochemical reduction of the 1,4,7-trithiacyclononane (9S3) complexes [MII(9S3)2][BF4]2 (M = Re (3a) or Tc (3b)) results in instantaneous C-S bond cleavage to yield ethene and the stable MIII thiolate complexes [MIII(9S3)L][BF4] (M = Re (4a) or Tc (4b), L = SCH2CH2SCH2CH2S). Compounds 4 have been characterized by 1H NMR spectroscopy, and the pseudo-octahedral geometry of 4b has been confirmed by X-ray crystallography. Upon electrochemical reduction 4a loses ethene, while 4b can be reversibly reduced to [TcII(9S3)L], which is then further reduced to Tc(I) with loss of ethene. Successive ethene loss is observed in the mass spectra of compounds 3 and 4. The radiosynthesis of 4a with 188Re can be comfortably completed within 10 min starting with 188ReO4- from a 188W/188Re generator, with a radiochemical yield in excess of 90%, and thus represents a practical approach to the preparation of stable 188Re (and 99mTc) thioether complex derivatives/conjugates for clinical use. Crystal data: 4b, C10H20S6Tc, orthorhombic Pbca, a = 12.233(2) A, b = 14.341(2) A, c = 20.726(3) A, Z = 8. PMID- 11198865 TI - Calix[4]arene rhenium(V) complexes as potential radiopharmaceuticals. AB - The calix[4]arene platform was used for the syntheses of novel rhenium(V) complexes, that may have potential applications as radiopharmaceuticals. The reaction of ReO(PPh3)2Cl3 with tetradentate N2O2-calix[4]arene ligand 8 in ethanol gave the novel mixed-ligand rhenium complex 9 with the structure ReO(N2O2 calix)OEt. The configuration was elucidated by using a number of 1H NMR techniques. In 9, the ethoxy ligand could be easily and quantitatively exchanged for another monodentate ligand to give complex 12. Tetradentate N2S2 calix[4]arene ligand 15 formed the rhenium complex 16 either via reaction with ReO(PPh3)2Cl3 in an organic solvent or by reaction with rhenium gluconate in an aqueous solution. Complex 16 showed good stability in phosphate-buffered saline solution (37 degrees C, 5 d). The crystal structures of a mono- and a bimetallic complex were determined. The bimetallic N2O2-calixarene complex dimer 11 crystallized in the monoclinic space group C2/c, with a = 38.963(5) A, b = 23.140(6) A, c = 27.382(6) A, beta = 128.456(10) degrees, V = 19,333(7) A3, Z = 8, and final R = 0.0519. The monometallic N2S2 model complex 17 crystallized in the monoclinic space group Cc, with a = 15.715(2) A, b = 12.045(2) A, c = 20.022(3) A, beta = 94.863(12) degrees, V = 3776.3(10) A3, Z = 4, and final R = 0.0342. PMID- 11198866 TI - Hydrolysis, hydrosulfidolysis, and aminolysis of imido(methyl)rhenium complexes. AB - The tris(imido)methylrhenium complex CH3Re(NAd)3 (1a, Ad = 1-adamantyl) reacts with H2O to give CH3Re(NAd)2O (2a) and AdNH2. The resulting di(imido)oxo species can further react with another molecule of H2O to generate CH3Re(NAd)O2 (3a). The kinetics of these reactions have been studied by means of 1H NMR and UV-vis spectroscopies. The second-order rate constant for the reaction of 1a with H2O at 298 K in C6H6 is 3.3 L mol-1 s-1, which is much larger than the value 1 x 10(-4) L mol-1 s-1 obtained for the reaction between CH3Re(NAr)3 (1b, Ar = 2,6 diisopropylphenyl) and H2O in CH3CN at 313 K. Both 1a and 1b react with H2S to produce the rhenium(VII) sulfide, (CH3Re(NR)2)2(mu-S)2 (4a, R = Ad; 4b, R = Ar), with second-order rate constants of 17 and 1.6 x 10(-4) L mol-1 s-1 in C6H6 and CH3CN, respectively. Complex 4b has been structurally characterized. The crystal data are as follows: space group C2/c, a = 30.4831 (19) A, b = 10.9766 (7) A, c = 18.1645 (11) A, beta = 108.268(1) degrees, V = 5771.5 (6) A3, Z = 4. The reaction between CH3Re(NAr)2O (2b) and H2S also yields the dinuclear compound 4b. Unlike 1b, 1a reacts with aniline derivatives to give mixed imido rhenium complexes. PMID- 11198867 TI - Kinetics and mechanisms of reactions of methyldioxorhenium(V) in aqueous solutions: dimer formation and oxygen-atom abstraction reactions. AB - The stable compound CH3ReO3 (MTO), upon treatment with aqueous hypophosphorous acid, forms a colorless metastable species designated MDO, CH3ReO2(H2O)n (n = 2). After standing, MDO is first converted to a yellow dimer (lambda max = 348 nm; epsilon = 1.3 x 10(4) L mol-1 cm-1). That reaction follows second-order kinetics with k = 1.4 L mol-1 s-1 in 0.1 M aq trifluoromethane sulfonic acid at 298 K. Kinetics studies as functions of temperature gave delta S++ = -4 +/- 15 J K-1 mol 1 and delta H++ = 71.0 +/- 4.6 kJ mol-1. A much more negative value of delta S++ would be expected for simple dimerization, suggesting the release of one or more molecules of water in forming the transition state. If solutions of the dimer are left for a longer period, an intense blue color results, followed by precipitation of a compound that does, even after a long time, retain the Re-CH3 bond in that aq. hydrogen peroxide generates the independently known CH3Re(O)(O2)2(H2O). The blue compound may be analogous to the intensely colored purple cation [(Cp*Re)3(mu 2-O)3(mu 3-O)3ReO3]+. If a pyridine N-oxide is added to the solution of the dimer, it is rapidly but not instantaneously lost at the same time that a catalytic cycle, separately monitored by NMR, converts the bulk of the PyO to Py according to this stoichiometric equation in which MDO is the active intermediate: C5H5NO + H3PO2-->C5H5N + H3PO3. A thorough kinetic study and the analysis by mathematical and numerical simulations show that the key step is the conversion of the dimer D into a related species D* (presumably one of the two mu-oxo bonds has been broken); the rate constant is 5.6 x 10(-3) s-1. D* then reacts with PyO just as rapidly as MDO does. This scheme is able to account for the kinetics and other results. PMID- 11198868 TI - Electron transfer. 144. Reductions with germanium(II). AB - Solutions 0.2-0.4 M in Ge(II) and 6 M in HCl, generated by reaction of Ge(IV) with H3PO2, are stable for more than 3 weeks and can be diluted 200-fold with dilute HCl to give GeCl3- preparations to be used in redox studies. Kinetic profiles for the reduction of Fe(III) by Ge(II), as catalyzed by Cu(II), implicate the odd-electron intermediate, Ge(III), which is formed from Cu(II) and Ge(II) (k = 30 M-1 s-1 in 0.5 M HCl at 24 degrees C) and which is consumed by reaction with Fe(III) (k = 6 x 10(2) M-1 s-1). A slower direct reaction between Ge(II) and Fe(III) (k = 0.66 M-1 s-1) can be detected in 1.0 M HCl. The reaction of Ge(II) with I3- in 0.01-0.50 M iodide is zero order in oxidant and appears to proceed via a rate-determining heterolysis of a Ge(II)-OH2 species (k = 0.045 s 1) which is subject to H(+)-catalysis. Reductions of IrCl6(2-) and PtCl6(2-) by Ge(II) are strongly Cl(-)-catalyzed. The Ir(IV) reaction proceeds through a pair of 1e- changes, of which the initial conversion to Ge(III) is rate-determining, whereas the Pt(IV) oxidant probably utilizes (at least in part) an inner-sphere PtIV-Cl-GeII bridge in which chlorine is transferred (as Cl+) from oxidant to reductant. The 2e- reagent, Ge(II), like its 5s2 counterpart, In(I), can partake in 1e- transactions, but requires more severe constraints: the coreagent must be more powerfully oxidizing and the reaction medium more halide-rich. PMID- 11198869 TI - C-substituted macrocycles as candidates for radioimmunotherapy. AB - The reaction between aryl aldehydes, the macrocyclic ligand 6-methyl-1,4,8,11 tetraazacyclotetradecane-6-amine (L1), and NaBH3CN produces the corresponding benzyl-substituted ligands in good yield. Copper(II) complexes of the ligands derived from salicylaldehyde (L2), p-hydroxybenzaldehyde (L4), and p carboxybenzaldehyde (L5) were structurally characterized: [CuL2](ClO4)2.3H2O (monoclinic, P2(1)/c, a = 11.915(6) A, b = 13.861(2) A, c = 17.065(8) A, beta = 102.14(2) degrees, Z = 4); [CuL4](ClO4)2 (monoclinic, P2(1)/n, a = 9.550(3) A, b = 17.977(2) A, c = 14.612(4) A, beta 96.76(1) degrees, Z = 4), and [CuL4](ClO4)2 (monoclinic, P2(1)/n, a = 9.286(2) A, b = 11.294(1) A, c = 23.609(8) A, beta 93.68(1) degrees, Z = 4). Conjugation of several CuII complexes to a protein (bovine serum albumin) has been pursued with a view to the application of these macrocycles as bifunctional chelating agents in radioimmunotherapy. PMID- 11198870 TI - Characterization of a new hexasodium diphosphopentamolybdate hydrate, Na6[P2Mo5O23]x7H2O, by 23Na MQMAS NMR spectroscopy and X-ray powder diffraction. AB - A novel hexasodium disphosphopentamolybdate hydrate, Na6[P2Mo5O23]x7H2O, has been identified using X-ray powder diffraction, 1H, 23Na, and 31P magic-angle spinning (MAS) NMR, and 23Na multiple-quantum (MQ) MAS NMR. Powder XRD reveals that the hydrate belongs to the triclinic spacegroup P1 with cell dimensions a = 10.090(3) A, b = 15.448(5) A, c = 8.460(4) A, alpha = 101.45(6) degrees, beta = 104.09(2) degrees, gamma = 90.71(5) degrees, and Z = 2. The number of water molecules of crystallization has been determined on the basis of a quantitative evaluation of the 1H MAS NMR spectrum, the crystallographic unit cell volume, and a hydrogen content analysis. The 23Na MQMAS NMR spectra of Na6[P2Mo5O23]x7H2O, obtained at three different magnetic fields, clearly resolve resonances from six different sodium sites and allow a determination of the second-order quadrupolar effect parameters and isotropic chemical shifts for the individual resonances. These data are used to determine the quadrupole coupling parameters (CQ and eta Q) from simulations of the complex line shapes of the central transitions, observed in 23Na MAS NMR spectra at the three magnetic fields. This analysis illustrates the advantages of combining MQMAS and MAS NMR at moderate and high magnetic fields for a precise determination of quadrupole coupling parameters and isotropic chemical shifts for multiple sodium sites in inorganic systems. 31P MAS NMR demonstrates the presence of two distinct P sites in the asymmetric unit of Na6[P2Mo5O23].7H2O while the 31P chemical shielding anisotropy parameters, determined for this hydrate and for Na6[P2Mo5O23]x13H2O, show that these two hydrates can easily be distinguished using 31P MAS NMR. PMID- 11198871 TI - Speciation and kinetics related to catalytic carbonylation in the presence of cis [Ir(CO)2I2]P(C6H5)4 under CO and H2 pressures. AB - The differences in the reactivities of the square-planar complexes cis [Rh(CO)2I2]- (1) and cis-[Ir(CO)2I2]- (2), involved in the catalytic carbonylation of olefins, are investigated, with P(C6H5)4+ as the counterion, by ambient- and high-pressure NMR and IR spectroscopy. Under an elevated pressure of CO, 1 and 2 form the [M(CO)3I] complexes with the equilibrium constants KIr approximately 1.8 x 10(-3) and KRh approximately 4 x 10(-5). The ratio KIr/KRh close to 50 shows that, under catalytic conditions (a few megapascals), only complex 1 remains in the anionic form, while a major amount of the iridium analogue 2 is converted to a neutral species. The oxidative addition reactions of HI with 1 and 2 give two monohydrides of different geometries, mer,trans [HRh(CO)2I3]- (3) and fac,cis-[HIr(CO)2I3]- (4), respectively. Both hydrides are unstable at ambient temperature and form, within minutes for Rh and within hours for Ir, the corresponding cis-[M(CO)2I2]- (1 or 2) and [M(CO)2I4]- (5 or 6) species and H2. When an H2 pressure of 5.5 MPa is applied to a nitromethane solution of complex 2, ca. 50% of 2 is transformed to cis-dihydride complexes. The formation of cis,cis,cis-[IrH2(CO)2I2]- (8a) is followed by intermolecular rearrangements to form cis,trans,cis-[IrH2(CO)2I2]- (8b) and cis,cis,trans [IrH2(CO)2I2]- (8c). A small amount of a dinuclear species, [Ir2H(CO)4I4]x- (9), is also observed. The formation rate constants for 8a and 8b at 262 K are k1(262) = (4.42 +/- 0.18) x 10(-4) M-1 s-1, k-1(262) = (1.49 +/- 0.07) x 10(-4) s-1, k2(262) = (2.81 +/- 0.04) x 10(-5) s-1, and k-2(262) = (5.47 +/- 0.16) x 10(-6) s 1. The two equilibrium constants K1(262) = [8a]/([2][H2]) = 2.97 +/- 0.03 M-1 and K2(262) = [8b]/[8a] = 5.13 +/- 0.10 show that complex 8b is the thermodynamically stable addition product. However, no similar H2 addition products of the rhodium analogue 1 are observed. The pressurization with H2 of a solution containing 2 and 6 give the monohydride 4, the dihydrides 8a and 8b, the dinuclear complex 9, and the two new complexes [Ir(CO)2I3] (10) and [HIr(CO)2I2] (11). The reactions of the iridium complexes with H2 and HI are summarized in a single scheme. PMID- 11198872 TI - Sc6MTe2 (M = Mn, Fe, Co, Ni): members of the flexible Zr6CoAl2-type family of compounds. AB - The compounds Sc6MTe2 (M = Mn, Fe, Co, Ni) have been prepared by high-temperature solid-state techniques and their structures determined to be hexagonal P62m (No. 189), Z = 1, a = 7.662(1) A, 7.6795(2) A, 7.6977(4) A, 7.7235(4) A and c = 3.9041(9) A, 3.8368(2) A, 3.7855(3) A, 3.7656(3) A for M = Mn, Fe, Co, and Ni, respectively. Crystal structures were refined for M = Fe and Ni, while M = Mn and Co were assigned as isostructural on the basis of powder diffraction data. The Sc6MTe2 compounds belong to a large family with the Zr6CoAl2-type structure, an ordered variant of the Fe2P structure. The structure contains confacial tricapped trigonal prisms of scandium centered alternately by the late transition metal or tellurium atoms. The Sc6MTe2 compounds are the electron-poorest examples of this structure type. Extended Huckel band calculations for M = Fe and Ni show that both compounds exhibit largely 1D metal-metal bonding and are predicted to be metallic. PMID- 11198873 TI - Azido derivatives of low-valent group 14 elements: synthesis, characterization, and electronic structure of [(n-Pr)2ATI]GeN3 and [(n-Pr)2ATI]SnN3 featuring heterobicyclic 10-pi-electron ring systems. AB - Treatment of THF solutions of [(n-Pr)2ATI]MCl (where [(n-Pr)2ATI]- = N-(n-propyl) 2-(n-propylamino)troponiminate; M = Ge and Sn) with sodium azide affords the compounds [(n-Pr)2ATI]MN3 in excellent yield. X-ray analyses revealed that these Ge(II) and Sn(II) compounds feature linear azide moieties and planar heterobicyclic C7N2M ring systems. Germanium and tin atoms adopt a pyramidal geometry. IR spectra of [(n-Pr)2ATI]GeN3 and [(n-Pr)2ATI]SnN3 display a nu asym(N3) band at 2048 and 2039 cm-1, respectively. DFT calculations on the corresponding methyl-substituted species demonstrate that the geometrical and electronic structure of these two species are very similar, and the dominant canonical form of the metal-azide moiety is M-N-N identical to N. The tin system is, as expected, slightly more ionic. A comparative CASSCF/DFT study on the model system H-Sn-N3 illustrates that the DFT approach is viable for the calculation of the structures of these species. PMID- 11198874 TI - Synthesis and molecular structure of a plutonium(IV) coordination complex: [Pu(NO3)2(2,6-[(C6H5)2P(O)CH2]2C5H3NO)2](NO3)2x1.5H2Ox0.5MeOH. AB - The trifunctional ligand 2,6-[(C6H5)2P(O)CH2]2 C5H3NO (1), in a mixed EtOH/MeOH solvent system, when combined with an aqueous nitric acid solution of Pu(IV), produces a 2:1 coordination complex, [Pu(1)2(NO3)2](NO3)2. A single crystal of [Pu(NO3)2(2,6-[(C6H5)2P(O)CH2]2C5H3NO)2](NO3)2x1.5H2Ox0.5MeOH was characterized by X-ray diffraction analysis. The crystal is monoclinic, space group P2(1)/n, with a = 19.1011(9) A, b = 18.2873(9) A, c = 21.507(1) A, alpha = gamma = 90 degrees, beta = 108.64(1) degrees, and Z = 4. Two neutral ligands (1) are bonded to the Pu(IV) ion in a tridentate fashion. Two nitrate ions also occupy inner sphere coordination positions, while two additional NO3- ions reside in the outer sphere. Comparison of the solution optical absorbance and solid diffuse reflectance spectra shows the same Pu(IV) chromophore exists in both solid and solution states. PMID- 11198875 TI - Plutonium(IV) sequestration: structural and thermodynamic evaluation of the extraordinarily stable cerium(IV) hydroxypyridinonate complexes. AB - Ligands containing the 1-methyl-3-hydroxy-2(1H)-pyridinone group (Me-3,2-HOPO) are powerful plutonium(IV) sequestering agents. The Ce(IV) complexes of bidentate and tetradentate HOPO ligands have been quantitatively studied as models for this sequestration. The complexes Ce(L1)4, Ce(L2)4, Ce(L3)2, and Ce(L4)2 (L1 = Me-3,2 HOPO; L2 = PR-Me-3,2-HOPO; L3 = 5LI-Me-3,2-HOPO; L4 = 5LIO-Me-3,2-HOPO) were prepared in THF solution from Ce(acac)4 and the corresponding ligand. The complex Ce(L4)2 was also prepared in aqueous solution by air oxidation of the Ce(III) complex [Ce(L4)2]-. Single-crystal X-ray diffraction analyses are reported for Ce(L1)(4)x2CHCl3 [P1 (no. 2), Z = 2, a = 9.2604(2) A, b = 12.1992(2) A, c = 15.9400(2) A, alpha = 73.732(1) degrees, beta = 85.041(1) degrees, gamma = 74.454(1) degrees], Ce(L3)2x2CH3OH [P2(1)/c (no. 14), Z = 4, a = 11.7002(2) A, b = 23.0033(4) A, c = 15.7155(2) A, beta = 96.149(1) degrees], Ce(L4)(2).2CH3OH [P1 (no. 2), Z = 2, a = 11.4347(2) A, b = 13.8008(2) A, c = 15.2844(3) A, alpha = 101.554(1) degrees, beta = 105.691(1) degrees, gamma = 106.746(1) degrees], and Ce(L4)2x4H2O [P2(1)/c (no. 14), Z = 4, a = 11.8782(1) A, b = 22.6860(3) A, c = 15.2638(1) A, beta = 96.956(1) degrees]. A new criterion, the shape measure S, has been introduced to describe and compare the geometry of such complexes. It is defined as [formula: see text], where m is the number of edges, delta i is the observed dihedral angle along the ith edge of delta (angle between normals of adjacent faces), theta i is the same angle of the corresponding ideal polytopal shape theta, and min is the minimum of all possible values. For these complexes the shape measure shows that the coordination geometry is strongly influenced by small changes in the ligand backbone or solvent. Solution thermodynamic studies determined overall formation constants (log beta) for Ce(L2)4, Ce(L3)2, and Ce(L4)2 of 40.9, 41.9, and 41.6, respectively. A thermodynamic cycle has been used to calculate these values from the corresponding formation constants of Ce(III) complexes and standard electrode potentials. From the formation constants and from the protonation constants of the ligands, extraordinarily high pM values for Ce(IV) are generated by these tetradentate ligands (37.5 for Ce(L3)2 and 37.0 for Ce(L4)2). The corresponding constants for Pu(IV) are expected to be substantially the same. PMID- 11198877 TI - Three-dimensional manganese(II) coordination polymers based on m pyridinecarboxylates: synthesis, X-ray structures, and magnetic properties. PMID- 11198876 TI - Syntheses, structures and magnetic behaviors of di- and trinuclear pivalate complexes containing both cobalt(II) and lanthanide(III) ions. PMID- 11198878 TI - A new porous three-dimensional lanthanide coordination polymer. PMID- 11198879 TI - The vanadium(V) borophosphate (NH4)5[V3BP3O19]xH2O. PMID- 11198880 TI - Weak ferromagnetism in a three-dimensional manganese(II) azido complex, [Mn(4,4' bipy)(N3)2]n (bipy = bipyridine). PMID- 11198881 TI - Colorectal cancer: evolving concepts in diagnosis, treatment, and prevention. PMID- 11198882 TI - Adjuvant therapy of colon cancer. AB - Adjuvant therapy, believed by some to be of no benefit for colorectal cancer as recently as 10 years ago, now offers thousands of patients considerable hope after surgical resection. The first effective adjuvant regimen--combined fluorouracil (5-FU) and levamisole--described in 1989, was soon supplanted by a variety of 5-FU-based regimens, usually combined with leucovorin. Although most recent research in the adjuvant setting has focused on refining chemotherapy doses, schedules, and combinations, with the aim of improving efficacy and decreasing toxicity, investigators have also explored other approaches, such as portal vein infusion, monoclonal antibodies, interferon-alpha, and vaccines. Future directions being evaluated for adjuvant therapy of colon cancer include the use of oral fluorinated pyrimidines, which may replace current intravenous treatments, as well as the incorporation of new agents, such as oxaliplatin and CPT-11, into adjuvant chemotherapy programs. PMID- 11198883 TI - Laparoscopic management of colorectal cancer. AB - Laparoscopic treatment of colorectal cancer has emerged as a result of the technical advances that have been made since the introduction of laparoscopic cholecystectomy. The minimal-access approach to treatment of benign disease results in smaller incisions, reduced length of hospital stay, and a faster return to productive life. Laparoscopic approaches to colon cancer must take into consideration the potential effects of the technique on tumor dissemination at the time of the surgical procedure, as well as rates of recurrence and overall survival. Several technical approaches to laparascopic colon resection have now become possible, utilizing either total intra-abdominal maneuvers or laparoscopic assisted techniques. Margins of resection and lymph node removal with the minimal access techniques compare favorably with those of open colectomy. Several series now show that early results utilizing laparoscopic resection for colorectal cancer are favorable but that routine implementation of this procedure should await confirmatory outcomes generated by well-done prospective clinical trials. PMID- 11198884 TI - Surgical therapy of hepatic colorectal metastasis. AB - This review summarizes data demonstrating the safety and efficacy of liver resection for colorectal metastases. Hepatic resection in appropriately selected patients remains the only potentially curative treatment for patients with such metastases. Recommendations for preoperative patient evaluation, patient selection, adjuvant therapy, and postoperative follow-up are presented. Other surgical modalities utilized in the treatment of unresectable or recurrent hepatic colorectal metastases, including ablative modalities and surgical delivery of regional chemotherapy, are described. PMID- 11198885 TI - Cytoreductive surgery and adjuvant immunotherapy: a new management paradigm for metastatic melanoma. AB - Although patients with metastatic disease are usually not offered surgery as part of their comprehensive treatment plan, the authors suggest that surgical reduction of the tumor burden may enhance the host immune response and create a favorable setting for the use of active specific immunotherapy. PMID- 11198886 TI - Dendritic cell-based immunotherapy for prostate cancer. AB - Dendritic cells are unique in their ability to stimulate naive T cells. These investigators have developed a prostate cancer vaccine using autologous dendritic cells as a vehicle to present prostate antigens to T cells in vivo. PMID- 11198887 TI - New "patient-friendly" version of clinical breast cancer guidelines. PMID- 11198888 TI - A new era of cancer immunotherapy: converting theory to performance. AB - The major impact of recent scientific advances, such as the discovery of genes and gene products, has been to facilitate development of immunotherapies based on the specific stimulation of immune reactions against characterized tumor antigens. PMID- 11198890 TI - Is there a safe place between terra firma and the slippery slope? PMID- 11198889 TI - T cell-based immunotherapy for cancer: a virtual reality? AB - The goal of harnessing the immune system to recognize tumor as "nonself" is not new. Now, thanks to new knowledge and new techniques, however, modalities that seek to activate the host immune system are becoming increasingly feasible as treatments for advanced malignancies. PMID- 11198891 TI - Oncology services in the ambulatory setting. Oncology Nursing Society. PMID- 11198892 TI - Prevention and reporting of medication errors. Oncology Nursing Society. PMID- 11198893 TI - The role of unlicensed assistive personnel in cancer care. Oncology Nursing Society. PMID- 11198894 TI - Taking time for support. PMID- 11198895 TI - Ameliorating the tension: use of forgiveness for healing. AB - PURPOSE/OBJECTIVES: To generate a grounded substantive theory of the process of forgiveness in patients with cancer. DESIGN: Qualitative approach, grounded theory. SETTINGS: Inpatient hospice, cancer support groups, homecare patients. SAMPLE: 25 adult patients with cancer between the ages of 35 and 88 (X = 62.4 years): 13 men and 12 women receiving active, palliative, or terminal treatment. METHODS: Using grounded theory methodology, open-ended interviews were transcribed verbatim and analyzed using constant comparative analysis and expert and participant validation. MAIN RESEARCH VARIABLE: Forgiveness as reflected in participants' past and current experiences. FINDINGS: Participants described hurtful events that initially caused severe negative emotional responses. Participants also described attempts to focus on living out priority values prompted by their cancer diagnosis. An escalating tension ensued between maintaining negative emotions and acting on personal values. Forgiveness was used to relieve this tension. Using several methods to gain perspective allowed resolving these negative emotions and living out priority values to various degrees. CONCLUSIONS: A cancer diagnosis promotes the rethinking of life priorities regardless of the stage of disease. For these participants, forgiveness was used to help clarify personal values and to help eliminate negative emotions from an inflicted hurt. IMPLICATIONS FOR NURSING PRACTICE: Nurses can facilitate the healing process by helping patients to identify and clarify priority values, recognizing appropriate definitions of forgiveness, using active listening or referral to help patients analyze their situations, encouraging active approaches to forgiving, and encouraging perseverance in the process. PMID- 11198896 TI - Oncology nurses' experiences with requests for assisted dying from terminally ill patients with cancer. AB - PURPOSE/OBJECTIVES: To explore oncology nurses' experiences with receiving requests for assisted dying from terminally ill patients with cancer. DESIGN: Descriptive, naturalistic. SETTING: RNs who identified themselves as direct care providers or clinical nurse specialist members of the Oncology Nursing Society. SAMPLE: 40 oncology nurses who responded to a randomized, sequential direct mailing submitted 48 stories for analysis. METHODS: Anonymously submitted written stories analyzed using Denzin's process of interpretive interactionism. MAIN RESEARCH VARIABLE: The experience of receiving a request for assisted dying. FINDINGS: Four main themes emerged from the thematic analysis: Control, Conflict, Covert Communication, and the Enduring Influence. Eleven subthemes included the Cry for Help, Hastening the Process, What if, Managing the Morphine, Countering With Palliative Care, Collision of Values, Sense of Distress, Dialogue Around the Request, Silent Knowing, the Unforgettable, and Reflections on Lessons Learned. CONCLUSIONS: Experiences included a mixture of direct-patient and family requests for pain relief, anticipatory fear of future pain, desire to end life before unacceptable deterioration, family requests to hasten the dying trajectory, and others. Stories reflected the larger societal struggle with desires to control life, health, and the dying process. IMPLICATIONS FOR NURSING PRACTICE: Nurses should be prepared to respond to such requests in a compassionate and helpful way that is respectful of both the patient's and the nurse's personal values. Diversity of individual values and priorities may trigger some patients to seek assistance in controlling the timing and circumstances of death. Thus, continued study of nurse, patient, and family member experiences with this ethical dilemma is warranted. PMID- 11198897 TI - Israeli oncology and nononcology nurses' attitudes toward physician-assisted dying: a comparison study. AB - PURPOSE/OBJECTIVES: To compare the attitudes of Israeli oncology and nononcology nurses toward physician-assisted dying (PAD) and its legalization and to determine the factors that may be related to their attitudes. DESIGN: Nonrandomized, correlational study. SETTING: A teaching hospital in Jerusalem, Israel. SAMPLE: 71 oncology nurses and 52 nurses working in the maternity and nursery departments. RESULTS: The majority of nurses supported PAD and its legalization, with the greatest support being given when a suffering patient was involved. In the vignettes dealing with the nurse-patient relationship, oncology nurses were significantly less likely than nononcology nurses to agree with PAD but more likely to stay with their patients while the lethal drug was being given. Nononcology nurses were more supportive of legalization than oncology nurses. Religious nurses and nurses who observed religious traditions were significantly less likely to support PAD or vote for its legalization. CONCLUSION: Israeli nurses generally are supportive of PAD. However, oncology nurses were less likely to support its practice. In addition, the more religious nurses considered themselves, the less likely they were to support the practice. IMPLICATIONS FOR NURSING PRACTICE: Israeli nurses need to be made aware of the ethical, social, and legal implications of PAD and its legalization for the Israeli nursing profession. In addition, more cross-cultural research on attitudes toward PAD needs to be conducted. PMID- 11198898 TI - A death with dignity in Oregon. AB - PURPOSE/OBJECTIVES: To inform readers about the Oregon Death With Dignity Act and present a compilation and summary of major arguments in debates regarding physician assistance in dying for the terminally ill. DATA SOURCES: Experience, medical records, the patient's physician and family, books, periodicals, legislative documents, and publications. DATA SYNTHESIS: The Oregon Death With Dignity Act became a legal option for terminally ill Oregon residents in October 1997. Persuasive psychological, theological, philosophical, and pragmatic arguments protest the Act as being irrational, immoral, contrary to medical ethics, and dangerous. Equally persuasive arguments advocate the Act as rational, moral, consistent with the practice of healing, and safe. CONCLUSIONS: Physician assistance in dying is a legal option for terminally ill patients in the State of Oregon. For such a practice to be "out of the closet," as well as legal, is novel. The debate about the appropriateness of this Act revolves around values and beliefs that are seasoned and cherished. IMPLICATIONS FOR NURSING PRACTICE: As the practice of the terminally ill requesting physician assistance to die moves into the realm of a rational patient choice and legal physician action, nurses increasingly will be faced with having to deal with their own beliefs, attitudes, and emotions regarding this issue. Nurses cannot hide behind glib responses, quick referals, institutional policies, or organizational standards to cover their own discomfort or confusion. They must discuss and formulate an understanding of healing and caring in situations that may challenge their core values. PMID- 11198899 TI - Spiritual needs of dying patients: a qualitative study. AB - PURPOSE/OBJECTIVES: To identify dying patients' definitions of spirituality and their spiritual needs. DESIGN: Descriptive, qualitative. SETTING: Participants' places of residence. SAMPLE: 19 hospice patients (10 females and 9 males), mean age 72, with a range of length of time as a hospice patient of 2 weeks to 12 months. METHODS: Semistructured interviews were conducted. Interview transcripts and field notes were analyzed to reduce data into codes and themes. Data were coded by extracting verbatim phrases used to describe spirituality and spiritual needs. Themes emerged from the data as commonalities among the codes developed. MAIN RESEARCH VARIABLES: Meaning of "spiritual" and perceived spiritual needs. FINDINGS: Participants initially defined spiritual as relating to God or religion; however, as interviews progressed, it was apparent that their spirituality was a part of their total existence. Twenty-nine unique spiritual needs were identified and grouped into six themes: need for religion, need for companionship, need for involvement and control, need to finish business, need to experience nature, and need for positive outlook. CONCLUSIONS: Participants perceived spirituality as a broad concept that may or may not involve religion. Spiritual needs were likewise broad in scope and were linked closely to purpose and meaning in life. IMPLICATIONS FOR NURSING PRACTICE: Spiritual care of dying patients is within the scope of nursing practice. Spiritual needs are quite varied and encompass more than religion. If nurses are to enhance the quality of life of dying patients, spiritual needs must be addressed. PMID- 11198900 TI - The relationships between family primary caregiver characteristics and satisfaction with hospice care, quality of life, and burden. AB - PURPOSE/OBJECTIVES: To examine relationships between family primary caregiver characteristics and satisfaction with hospice care, quality of life (QOL), and burden. DESIGN: Exploratory, quantitative. SETTING: Five hospice organizations in Eastern Washington and Northern Idaho. SAMPLE: 44 primary caregivers of patients enrolled in hospice for more than two weeks. METHODS: Telephone surveys measured primary caregivers' satisfaction with hospice care, QOL, and burden. Demographic, personal, and situational characteristics were compiled. Multivariate regression techniques were used to identify caregiver characteristics that explained the most variation in satisfaction with hospice care, QOL, and burden. MAIN RESEARCH VARIABLES: Satisfaction with hospice care, QOL, and burden. FINDINGS: Being retired, being a wife or daughter, patient diagnosis, per diem rate paid to the hospice organization, county population and density, length of time in hospice, and length of time as a caregiver were significantly related to satisfaction with hospice care, QOL, and burden. Age, sex, education level, occupation, income, patient functional status, and social support were not related to these variables. CONCLUSION: Although caregivers reported satisfaction with hospice care, the caregiver role negatively affects their QOL and they are burdened. "At risk" caregivers are still working, have been providing care for a long time, and live in a rural locale. IMPLICATIONS FOR NURSING PRACTICE: These findings create a profile of "typical" and "at-risk" primary caregivers and support the role of hospice to care for family caregivers. PMID- 11198901 TI - Changes in well-being of women cancer survivors following a survivor weekend experience. AB - PURPOSE/OBJECTIVES: To determine the long-term effects on quality of life (QOL) of women cancer survivors following a retreat experience. DESIGN: One-group repeated measures. SETTING: Southern California. SAMPLE: Participants in two 1998 Healing Odyssey Retreats (N = 41; response rate 67%). Most women were married (50%), had breast cancer (93%), and had been diagnosed within two years of the retreat (69%). Participants' mean age was 48 years. METHODS: The rehabilitative retreats took place in a mountain retreat center and consisted of multiple experiences guided by experiential learning theory. Exercises aimed to help women learn new tools for dealing with the challenges of cancer, treatment, and recovery. The QOL-Breast Cancer survey was used to collect data preretreat, immediately postretreat, at six weeks postretreat, and at six to seven months postretreat. MAIN RESEARCH VARIABLES: QOL subscale scores (physical, psychological, social, and spiritual well-being) and overall QOL scores. FINDINGS: At preretreat, women scored lower on psychological and social well being than on physical and spiritual well-being. Total QOL, physical, psychological, and spiritual well-being scores differed significantly over time, with a significant increase immediately following the retreat that was maintained at six weeks and six months. Social well-being at six months was significantly greater than at the other three points. CONCLUSIONS: The Healing Odyssey Retreats enhanced women cancer survivors' total QOL-specifically their well-being in four dimensions. IMPLICATIONS FOR NURSING PRACTICE: Women who seek programs dealing with living life more fully after cancer and connections with other survivors may benefit from rehabilitative efforts such as this retreat. PMID- 11198902 TI - Developing and using preparatory information for women undergoing radiation therapy for cervical or uterine cancer. AB - PURPOSE/OBJECTIVES: To describe symptoms associated with radiation therapy necessary to develop preparatory concrete, objective information for women with cervical or uterine cancer. DESIGN: Prospective, descriptive. SETTING: University affiliated radiation oncology department in the mid-south. SAMPLE: 49 of 52 women undergoing external beam radiation and low-dose rate brachytherapy for cervical or uterine cancer. Stage of disease ranged from I-IIIA. Mean age of subjects was 54 years; mean years of education was 11. METHODS: Investigator-developed symptom checklist based on prior research. MAIN RESEARCH VARIABLES: Symptom reports. FINDINGS: At least 40% of the women reported difficulty sleeping, fatigue, diarrhea, anorexia, nausea, urinary frequency, dysuria, vaginal discharge, and perineal irritation. Incidence and timing of symptoms varied by operative status and brachytherapy timing. CONCLUSIONS: Findings confirm and clarify the symptoms women associate with radiation treatment for cervical or uterine cancer. IMPLICATIONS FOR NURSING PRACTICE: Assessing research findings for relevance to the care of patients in specific settings is necessary. These findings are appropriate for developing preparatory information for women undergoing external beam radiation and low-dose rate brachytherapy. PMID- 11198903 TI - Relationships between certification and job perceptions of oncology nurses. AB - PURPOSE/OBJECTIVES: To explore relationships between oncology nursing certification and oncology nurses' job perceptions. DESIGN: Descriptive, correlational. SETTING: Questionnaire mailed to homes of Oncology Nursing Society (ONS) members. SAMPLE: 703 certified and 514 noncertified ONS members (N = 1,217; 50% response rate). METHODS: Data were collected using survey methods and grouped by respondents' certification status for statistical analysis. MAIN RESEARCH VARIABLES: Certification, group cohesion, organizational commitment, and job satisfaction. FINDINGS: Certification was weakly correlated with cohesion, commitment, and satisfaction. Work setting, rather than certification, accounted for differences in job perceptions. Job perceptions were most positive in settings characterized by a high percentage of patients with cancer (> 75%), a high percentage of RNs (> or = 80%), and monetary support for continuing education. CONCLUSIONS: The hypothesis that oncology nurses' certification status is associated with job perceptions that are valued by employers was not supported. IMPLICATIONS FOR NURSING PRACTICE: Nurses' job perceptions have been linked to control over nursing practice and participation in organizational and clinical decision making. Managerial strategies that empower certified nurses to practice with more autonomy and participate in decisions that affect patient care should be emphasized. PMID- 11198904 TI - Using feedback to reduce students' judgment bias on test questions. AB - Judgment bias represents a common tendency of people to inaccurately gauge the extent of their own knowledge. While research has shown that people tend to overestimate their knowledge on hard questions and underestimate their knowledge on easy questions, overconfidence poses a more pernicious problem from an educational perspective since it can undermine students' ability to monitor their own learning effectively and interfere with their test performance. The findings of the present study show that students who perform poorly on a test are more overconfident about their answers to hard test questions, especially those they answer wrongly, than are students who perform better. The results also show that judgment bias can be reduced by providing feedback to students about their prior performance and confidence on specific test questions. This intervention was found to be effective in decreasing both underconfidence on easy questions and overconfidence on hard questions regardless of students' performance level. PMID- 11198905 TI - Writing multiple-choice test items that promote and measure critical thinking. AB - Faculties are concerned about measurement of critical thinking especially since the National League for Nursing Accrediting Commission cited such measurement as a requirement for accreditation (NLNAC, 1997). Some writers and researchers (Alfaro-LeFevre, 1995; Blat, 1989; McPeck, 1981, 1990) describe the need to measure critical thinking within the context of a specific discipline. Based on McPeck's position that critical thinking is discipline-specific, guidelines for developing multiple-choice test items as a means of measuring critical thinking within the discipline of nursing are discussed. Specifically, criteria described by Morrison, Smith, and Britt (1996) for writing critical-thinking multiple choice test items are reviewed and explained for promoting and measuring critical thinking. PMID- 11198906 TI - Assessment of multiple-choice questions in selected test banks accompanying text books used in nursing education. AB - The purpose of this study was to assess multiple-choice questions used in test banks accompanying selected nursing textbooks. A random sample of 2,913 questions was selected from a convenience sample of 17 test banks. Questions were evaluated on (a) adherence to generally accepted guidelines for writing multiple-choice questions; (b) cognitive level as defined by Bloom's (1961) taxonomy; and (c) distribution of correct answers as A, B, C, or D. The results were 2,233 violations of item-writing guidelines, most of which were minor but some were serious. A large number of questions (47.3%) were written at the knowledge level and only 6.5% were written at the analysis level. The correct answers were evenly distributed: c2s ranged from 0.00 to 4.84; chi square value needed to reach .05 probability was 26.30. Faculty are encouraged to evaluate multiple-choice questions from test banks carefully before using them for exams. PMID- 11198907 TI - Measurement and evaluation in nursing education. PMID- 11198908 TI - Validating nursing credit: an alternative to challenges. PMID- 11198909 TI - Clinical performance appraisal: renewing graded clinical experiences. PMID- 11198910 TI - Case study class tests: assessment directing learning. PMID- 11198911 TI - The use of the cognitive behavior survey to assess nursing student learning. PMID- 11198912 TI - External examiners: quality assurance in nursing education. AB - External examining is a system of quality assurance in nursing education that is quite foreign to most American nurses. The concept of an external examiner-a visiting assessor of high academic standing and possessed of integrity and objectivity-supports a notion of the universality of educational standards and justice for the individual student. Potential external examiners are appointed primarily through informal social and professional networks within educational institutions of the host country. Criteria for appointment, roles and functions of an examiner, and the four stages of the external examination process are discussed. Suggestions to facilitate each stage as well as implications for potential American external examiners are included. The manuscript concludes with insights from two American nurse educators about their experience as external examiners. PMID- 11198913 TI - The abundance and seasonal distribution of Culex mosquitoes in Iowa during 1995 97. AB - The abundance and seasonal distribution of Culex mosquitoes were monitored by measuring oviposition activity during the summers of 1995, 1996, and 1997. Five species of culicine mosquitoes laid egg rafts in ovitraps. Egg rafts of 4 Culex species-Cx. restuans (54.98%), Cx. pipiens (25.41%), Cx. salinarius (12.18%), and Cx. tarsalis (0.14%)-constituted more than 92% of the total egg rafts collected. Culiseta inornata (0.1%) was the only other species to lay viable egg rafts in the ovitraps. A small percentage (7.19%) of egg rafts did not hatch; thus identification was not possible. Compared with New Jersey light trap data in a nearby area, the abundance of Cx. tarsalis and Cs. inornata was markedly underestimated with ovitraps. These data may also reflect differences in the specific location of the 2 trap sites rather than attractiveness of ovitraps for Cx. tarsalis and Cs. inornata. In general, Cx. restuans oviposition activity began in late May, and it was the dominant Culex species through June. After July 1, the number of egg rafts laid by Cx. restuans decreased continually until the end of the summer. Culex pipiens and Cx. salinarius oviposition began in early June and increased gradually during the summer. Over the course of a summer, there were about twice as many Cx. pipiens as there were Cx. salinarius. A crossover in the number of Cx. pipiens and Cx. restuans egg rafts occurred in late July or early August, depending on the year. By late August each year, Cx. pipiens was the most abundant species. At this time, Cx. restuans and Cx. salinarius populations were similar, but each was about half of the Cx. pipiens population. Differences in the abundance of all 3 species could not be explained by changes in ambient temperature (both minimum and maximum) or relative humidity, either within or among years. PMID- 11198914 TI - Anopheline ecology and malaria transmission at a new irrigation project area (Bargi Dam) in Jabalpur (Central India). AB - Anopheline ecology and malaria transmission were studied in a newly irrigated area of the Bargi Project, District Jabalpur, Madhya Pradesh, Central India. Observations were made for 2 years (1993-95) in 10 villages along the Bargi irrigation canal, which are situated between 44 km (head end of canal) and 78 km (tail end of canal) from the dam site. Anopheles annularis was the predominant species in the head-end villages and its abundance was directly related to the opening of the canal, whereas Anopheles culicifacies was the most abundant species in tail-end villages, where irrigation is limited. Anopheles culicifacies showed 2 typical peaks not related to canal irrigation. Site-related differences in species prevalence were significant in both immatures and adults. Malaria infection was due to Plasmodium vivax and Plasmodium falciparum. The annual parasite incidence in children and adults was significantly higher in head-end villages (>4-fold) as compared to that in tail-end villages. However, seasonal trends in the prevalence of P. falciparum and P. vivax were the same in each group, with some fluctuations. In this study, preliminary results of the investigation are presented, demonstrating the trends in anopheline ecology and parasite prevalence in relation to the dynamics of irrigation development. PMID- 11198915 TI - Comparative development of Brugia pahangi and variation in acid hydrolase enzyme titers in. AB - The development of the filarial nematode Brugia pahangi was monitored and compared in susceptible (BLACK EYE) and refractory (ROCK) strains of Aedes aegypti. Simultaneously, the activities of acid phosphatase, beta-glucuronidase, alpha-glucosidase, and N-acetyl-beta-glucosaminidase were measured. Three- to five-day-old females of both strains were fed on infected and uninfected clawed jirds (Meriones unguiculatus) then dissected or homogenized at 2 h, at 24-h intervals for 5 days, and at 8 and 10 days after treatment. Enzyme activities were assayed by a fluorometric procedure. The susceptible strain maintained an 80% infection and 18.6 larvae/mosquito over the 10-day period. In contrast, the refractory strain was initially 33% infected and had a mean of 4.9 larvae/mosquito and this decreased to 20% by 3 days, and to 3% with a mean of 0.33 larvae/mosquito at 10 days. Significantly higher acid phosphatase and beta glucuronidase activities were observed in the refractory strain at specific time intervals after infection. Alpha-glucosidase and N-acetyl-beta-glucosaminidase were highly variable among strains and according to infection status. Analysis of the results of this study suggests that certain acid hydrolase enzymes could be involved in the elimination of B. pahangi in refractory strains of Ae. aegypti and could be used to monitor biochemical changes in response to filarial nematode infections in certain mosquito populations. PMID- 11198916 TI - Mosquito vector control and biology in Latin America--a tenth symposium. Abstracts. AB - The 10th annual Latin American symposium presented by the American Mosquito Control Association (AMCA) was held as part of the 66th Annual Meeting in Atlantic City, NJ, in March 2000. The principal objective, as for the previous 9 symposia, was to promote participation in the AMCA by vector control specialists, public health workers, and academicians from Latin America. This publication includes summaries of 57 presentations that were given orally in Spanish or presented as posters by participants from 9 countries in Latin America. Topics addressed in the symposium included results from chemical and biological control programs and studies; studies of insecticide resistance; and molecular, ecological, and behavioral studies of vectors of dengue (Aedes aegypti). malaria (Anopheles albimanus and Anopheles aquasalis). leishmaniasis (Lutzomyia), and Chagas' disease (Triatoma). Related topics included biology and control of scorpions and Chironomus plumosus. PMID- 11198917 TI - Evaluation of Agnique MMF in man-made ponds for the control of pestiferous chironomid midges (Diptera: Chironomidae). AB - The efficacy of a monomolecular surface film, Agnique MMF (a liquid isostearyl alcohol ethoxylate containing 2 oxyethylene groups [ISA-2OE]) in suppressing emergence of adult Chironomidae from man-made earthen ponds was studied. Three replicated rates, 0.23, 0.47, and 0.94 ml/m2 (or 0.25, 0.5, and 1.0 gal/acre) of Agnique MMF were applied. Pretreatment and periodic posttreatment samples of adult chironomids were collected by employing submerged metal-cone traps as well as floating traps. Concurrently, water pH, dissolved oxygen, specific conductance, and water temperature were measured. Tanytarsini (>82%), Chironomini (16%), and Tanypodinae (1%) midges were collected during the study period. Midge adult collections in floating traps were not significantly reduced by the 0.23 ml/m2 treatment rate, but were significantly reduced (73-93%) for 1-2 wk posttreatment at 0.47 and 0.94 ml/m2 of Agnique MME The lowest rate significantly reduced midge adult emergence for 1 day posttreatment as measured by metal-cone traps, whereas the 2 higher rates reduced emergence by 78.6-97% for 1 wk posttreatment. Using either trap, the highest rate of Agnique MMF did not produce suppression of adult midges of any greater magnitude or duration than the middle rate. Agnique MMF was not detected by the indicator oil in any treated pond after 7 days posttreatment. Water pH, dissolved oxygen, specific conductance, and water temperature in the ponds were not significantly influenced by Agnique MMF treatments. Analysis of these data supports the possible use of Agnique MMF for chironomid control in areas where the surface film of this material can be maintained for sufficient time to interfere with adult emergence. PMID- 11198918 TI - Control of aedes aegypti breeding in desert coolers and tires by use of Bacillus thuringiensis var. Israelensis formulation. AB - Three different formulations of Bacillus thuringiensis var. israelensis (Bti) were evaluated for their efficacy against immature Aedes aegypti in desert coolers and tires. Three formulations, viz., VectoBac tablets, VectoBac granules, and Bacticide powder, at the application rate of 0.75, 2, and 1 g per cooler, respectively, and VectoBac tablets at 0.75 and 0.375 g per tire, were evaluated. In coolers and tires, 100% reduction in the abundance of late larval instars of Ae. aegypti was observed for a period of 2 and 3 wk, respectively. The possibility of using tablets and capsules filled with Bti granules and powder formulation by individuals or communities for control of Ae. aegypti breeding has been discussed in view of the increasing outbreaks of dengue and dengue hemorrhagic fever in India. Use of these formulations over conventional methods is better and more user-friendly. PMID- 11198919 TI - Malathion resistance in Aedes aegypti and Culex quinquefasciatus after its use in Aedes aegypti control programs. AB - The continued widespread use of malathion in Aedes aegypti control programs in Latin America has generated insecticide resistance to this chemical in Culex quinquefasciatus but not in Ae. aegypti. To determine the extent of this resistance, the susceptibility of Cx. quinquefasciatus and Ae. aegypti from several countries to malathion was evaluated. Bioassay results indicated that all Ae. aegypti strains evaluated from Cuba, Venezuela, Costa Rica, and Jamaica were susceptible to malathion in spite of the historical use of this insecticide in Ae. aegypti control programs in these countries. In contrast, a high level of resistance to this insecticide was found in Cx. quinquefasciatus from Venezuela, Colombia, Brazil, and Cuba. Synergist assays indicated that neither esterases nor mixed-function oxidases (MFOs) were involved as the resistance mechanism to malathion in any of the Ae. aegypti strains tested. In Cx. quinquefasciatus, synergist assays confirmed that esterases played an important role in malathion resistance but MFOs were not involved in causing malathion resistance in this species. Biochemical assays showed that both resistance mechanisms were present in the Ae. aegypti and Cx. quinquefasciatus populations. Acrylamide electrophoresis gels revealed that all Ae. aegypti strains had a strongly staining, clear band, named A4, and had a relative mobility (Rm) value of 0.7. Analysis if the results of this study suggested that malathion could continue to be used for the emergency control of Ae. aegypti, the mosquito vector for dengue and dengue hemorrhagic fever in the Americas, but that malathion is probably not effective for the control of adult Cx. quinquefasciatus in urban areas. Therefore, control operations should integrate nonorganophosphate insecticides such as pyrethroids for control of these 2 species found in the urban environment. PMID- 11198920 TI - Insecticide susceptibility in Anopheles pseudopunctipennis from Colombia: comparison between bioassays and biochemical assays. AB - Anopheles pseudopunctipennis, one of the primary vectors of malaria in the southwest of Colombia, was evaluated for susceptibility to the 3 major insecticide groups (organophosphates, pyrethroids, and carbamates) by bioassay and biochemical assay. Larval populations, which were collected principally from irrigation channels in agricultural areas, where the intensity of insecticide use varied, were utilized to establish susceptibility for the 1st time in this species. The baselines for each population showed a range of biological susceptibility to the insecticides evaluated, but overall no resistance was detected according to standards established by the World Health Organization. The high sensitivity of biochemical microassays enabled the detection of a small proportion of mosquitoes with higher levels of nonspecific esterases and mixed function oxidases from 2 areas where agricultural application of organophosphate and pyrethroid insecticides had been heavy. These differences were not sufficient to affect susceptibility as measured by bioassay. No evidence of insensitive acetylcholinesterase was observed. Absence of resistance in areas that have experienced heavy insecticide application could be explained by genetic drift, by gene flow from areas without insecticide pressure, by manner of exposure to the insecticides, or by recent changes in agricultural activities that decreased insecticide use. Baseline values were established that serve as provisional susceptibility thresholds for applying simple Centers for Disease Control and Prevention biochemical assay and bioassay methods to larvae of this anopheline species. PMID- 11198921 TI - Aircraft-mediated mosquito transport: new direct evidence. AB - A case is reported of a capture of an Aedes taeniorhynchus female mosquito in an aircraft cabin as it attempted to bloodfeed on one of the authors during a transoceanic flight from the USA to the Iberian Peninsula. PMID- 11198922 TI - Seasonal incidence of Aedes (Rhinoskusea) portonovoensis in a mangrove forest of South India. AB - The seasonal incidence of Aedes (Rhinoskusea) portonovoensis in its type locality is reported. This is the Ist information on the bionomics of this species described from a mangrove forest in South India. Peak density of adults occurred in August. The larval habitat of the species is also defined. PMID- 11198923 TI - Evaluation of methylated soy oil and water-based formulations of Bacillus thuringiensis var. Israelensis and Golden Bear Oil (GB-1111) against anopheles quadrimaculatus larvae in small rice plots. AB - The efficacy of formulations containing methylated soybean oil (MSO) alone and with technical-grade Bacillus thuringiensis var. israelensis (Bti) were compared to Golden Bear Oil (GB-1111) and a water-based Bti formulation against 3rd- to 4th-stage Anopheles quadrimaculatus larvae confined to sentinel cages in small rice plots. Three replicates each of MSO with 2% Pyroter added as a surfactant (MSO + PYR), MSO with 2% Pyroter and 4 g of Bti technical powder (MSO + PYR + Bti), GB-1111, a water-based formulation with 4 g of Bti technical powder (Bti + water), and untreated controls were performed. Mosquito larvae were introduced on the 1st day of treatment and at 4 days posttreatment. Mortality was recorded at 24 and 48 h posttreatment for the 1st installation and at 5 days posttreatment for the 2nd installation. The Bti + water formulation provided 71% control and the MSO + PYR + Bti formulation achieved 64% control, whereas MSO + PYR and GB 1111 produced 16 and 18% control, respectively, at 24 h posttreatment. With the exception of MSO + PYR + Bti, which decreased by 2%, the mean percent control increased slightly at 48h posttreatment across remaining treatments, with Bti + water obtaining 72% control. This was significantly higher than GB-1111, which achieved 23% control at 48 h posttreatment. The MSO + PYR and MSO + PYR + Bti formulations yielded 56 and 62% control, respectively, during the same interval and were not significantly different from one another. Formulations containing MSO + PYR exhibited delayed activity similar to GB-1111, with all formulations except MSO + PYR + Bti providing greatest control at 48 h posttreatment. Both MSO formulations (MSO + PYR + Bti and MSO + PYR) were statistically comparable to Bti + water and GB-1111, respectively, at 24 and 48 h posttreatment. None of the formulations exhibited a residual activity adequate enough to control An. quadrimaculatus larvae for up to 5 days. PMID- 11198924 TI - Inhibition of interleukin-1beta (IL-1beta) production in human cells by ribozymes against IL-1beta and IL-1beta converting enzyme (ICE). AB - We and others have shown previously that hairpin ribozyme genes, when stably expressed in cells, can reduce the steady-state levels of target mRNA and their cognate proteins. Despite this capability, ribozymes have not been as widely used in knockdown experiments as one might expect, probably because specific rules governing the selection of ribozymes that will have high activity have not been described. In this report, we show that parallel screening of less than 10 ribozyme expression constructs, with no advanced knowledge of cleavage activity or preselection, can efficiently identify knockdown ribozymes. This empirical selection study, which used interleukin-1beta (IL-1beta) and IL-1beta converting enzyme (ICE) as example targets, resulted in (1) the rapid identification of ribozymes that can reduce the production of IL-1beta in THP-1 cultures by 10-fold and (2) the consequent direct generation of stable knockdown cell lines. We conclude, based on these and similar studies, that parallel screening of ribozyme constructs could be used in high throughput gene functional analysis programs as a means of rapidly generating specific knockdown cell lines. PMID- 11198925 TI - In vivo expression of single-stranded DNA in mammalian cells with DNA enzyme sequences targeted to C-raf. AB - The use of antisense oligodeoxynucleotides (AS-ODN) remains a viable method to downregulate selected gene function. However, limitations to the antisense approach remain, such as (1) difficulties in delivery of the AS-ODN into target tissues, (2) instability of AS-ODN in vivo, (3) uncertanties about the precise mode of action, and (4) toxic effects in animal and human studies. To circumvent some of these difficulties, we designed a vector set that directs the in vivo production of single-stranded DNA (ssDNA) of a desired target sequence with limited extraneous vector nucleotide sequences. One plasmid was designed to express Moloney murine leukemia virus (MoMuLV) reverse transcriptase (RT). Another expression plasmid contains the MoMuLV primer binding site at the 3'-end of its RNA transcript so that an ssDNA would be synthesized by RT when both plasmids are cotransfected into cells. To test this expression system, we constructed a plasmid set, pssXA/pssXB that produces ssRNA-cleaving DNA 10-23 enzyme (Santoro, S.W., and Joyce, G.F. [1997]. Proc. Natl. Acad. Sci. USA 37, 13330-13342). The DNA enzyme sequence was placed between two oligonucleotide arms that are complementary and able to specifically target C-raf kinase mRNA. These plasmids were transfected into the A549 lung carcinoma cell line. Reduced C-raf mRNA levels by up to 34%-36%, as determined by Northern blot analysis, were observed in the transfected cells. Our results demonstrate the feasibility of using this novel ssDNA expression system to generate any sequence of interest in vivo for antisense, RNA-cleavage DNA enzyme, or triplex-forming strategies. PMID- 11198926 TI - Oligonucleotide sequence-specific inhibition of gene expression, tumor growth inhibition, and modulation of cAMP signaling by an RNA-DNA hybrid antisense targeted to protein kinase A RIalpha subunit. AB - The primary mediator of cAMP action in mammalian cells is cAMP-dependent protein kinase (PKA). There are two types of PKA, type I (PKA-I) and type II (PKA-II), which share a common catalytic subunit but contain distinct regulatory subunits, RI and RII, respectively. Evidence suggests that increased expression of RIalpha/PKA-I correlates with neoplastic cell growth. Here, we show that sequence specific oligonucleotide inhibition of RIalpha expression results in inhibition of growth and modulation of cAMP signaling in cancer cells. The antisense promoted growth inhibition in a time-dependent, concentration-dependent, and sequence-dependent manner in human cancer cells in monolayer culture, and it inhibited colony formation in soft agar and tumor growth in nude mice. Among the cancer cells are LS-174T, HCT-15, and Colo-205 colon carcinoma cells; A-549 lung carcinoma cells; LNCaP prostate adenocarcinoma cells; Molt-4 leukemia cells; and Jurkat T lymphoma cells. Northern blot and immunoprecipitation analyses revealed that the growth inhibitory effect of the antisense correlated with a decrease in RIalpha expression at both the mRNA and protein levels. Pulse-chase experiments revealed that the antisense-directed inhibition of RIalpha expression resulted in compensatory changes in expression of the isoforms of R and C subunits and cAMP signaling in a cell type-specific manner. These results demonstrate that cAMP is ubiquitous in the regulation of cell growth and that the antisense oligonucleotide, which inhibits the synthesis of the RIalpha subunit of PKA, can be targeted to a single gene for treatment of cancer in a variety of cell types. PMID- 11198927 TI - Comparison of the pharmacokinetics of subcutaneous and intravenous administration of a phosphorothioate oligodeoxynucleotide in cynomolgus monkeys. AB - The pharmacokinetics of subcutaneous (s.c.) administration of a phosphorothioate oligodeoxynucleotide (PS-ODN) was evaluated in cynomolgus monkeys. In a single dose study, monkeys were injected s.c. or intravenously (i.v.) with doses of either 1 or 5 mg/kg ISIS 2302. The bioavailability of s.c. injection ranged from 26% to 55% and appeared to be dependent on the concentration of the dosing solution rather than the dose. The bioavailability of a subcutaneously administered 5 mg/kg dose of ISIS 2302 was 55% using a 50 mg/ml dosing solution and only 26% using a 10 mg/ml dosing solution. Slow absorption from the s.c. injection site significantly blunted the maximal concentration (Cmax) compared with i.v. administration. The time to peak plasma concentration (Tmax) increased slightly with increasing dose, from 0.5 to 1 hour for the 1 mg/kg dose to 1 to 2.5 hours for the 5 mg/kg dose. Plasma half-lives were prolonged after s.c. administration, indicating more dependence on absorption than elimination. The half-lives after s.c. administration averaged 3 hours, whereas after i.v. administration, the half-lives were <1 hour. Metabolism of the ISIS 2302 after s.c. injection was consistent with exonucleolytic cleavage, as previously observed after i.v. administration. In summary, s.c. administration of PS-ODN resulted in prolonged and extensive absorption of the ODN. PMID- 11198928 TI - Targeting the human mdr1 gene by 125I-labeled triplex-forming oligonucleotides. AB - Antigene radiotherapy is our approach to targeting specific sites in the genome by combining the highly localized DNA damage produced by the decay of Auger electron emitters, such as 125I, with the sequence-specific action of triplex forming oligonucleotides (TFO). As a model, we used the multidrug resistance gene (mdr1) overexpressed and amplified nearly 100 times in the human KB-V1 carcinoma cell line. Phosphodiester pyrrazolopyrimidine dG (PPG)-modified TFO complementary to the polypurine-polypyrimidine region of the mdr1 gene were synthesized and labeled with 125I-dCTP at the C5 position of two cytosines by the primer extension method. 125I-TFO were delivered into KB-V1 cells with several delivery systems. DNA from the 125I-TFO-treated cells was recovered and analyzed for sequence-specific cleavage in the mdr1 target by Southern hybridization. Experiments with plasmid DNA containing the mdr1 polypurine-polypyrimidine region and with purified genomic DNA confirmed the ability of the designed 125I-TFO to bind to and introduce double-strand breaks into the target sequence. We showed that 125I-TFO in nanomolar concentrations can recognize and cleave a target sequence in the mdr1 gene in situ, that is, within isolated nuclei and intact digitonin-permeabilized cells. Our results demonstrate the ability of 125I-TFO to target specific sequences in their natural environment, that is, within the eukaryotic nucleus. The nearly 100-fold amplification of the mdr1 gene in KB-V1 cells affords a very useful cell culture model for evaluation of methods to produce sequence-specific DNA double-strand breaks for gene-specific radiotherapy. PMID- 11198929 TI - Variations in mRNA content have no effect on the potency of antisense oligonucleotides. AB - A fundamental question with regard to antisense pharmacology is the extent to which RNA content or transcription rate or both affect the potency of antisense drugs. We have addressed this by controlling RNA content and transcription rate using either an exogenous gene expressed after transfection or an endogenous gene induced with a cytokine. We have demonstrated that in both A549 and HeLa cells, varying RNA copy numbers from <1 to >100 copies per cell has no effect on the potency of RNase H-active antisense drugs transfected into cells, nor did variation in transcription rate have an effect on potency. We demonstrate that this is because the number of oligonucleotide molecules per cell is vastly in excess of the RNA copy number. These data further suggest that a significant fraction of cell-associated antisense drug molecules may be unavailable to interact with the target RNA, an observation that is not surprising, as phosphorothioate oligonucleotides interact with many cellular proteins. We suggest that these data may extrapolate to in vivo results. PMID- 11198930 TI - A short phosphodiester window is sufficient to direct RNase H-dependent RNA cleavage by antisense peptide nucleic acid. AB - The potential pharmacologic benefits of using peptide nucleic acid (PNA) as an antisense agent are tempered by its incapacity to activate RNase H. The mixed backbone oligonucleotide (ON) (or gapmer) approach, in which a short internal window of RNAse H-competent residues is embedded within an RNase H-incompetent ON has not been applied previously to PNA because PNA and DNA hybridize to RNA with very different helical structures, creating structural perturbations at the two PNA-DNA junctions. It is demonstrated here for the first time that a short internal phosphodiester window within a PNA is sufficient to evoke the RNase H dependent cleavage of a targeted RNA and to abrogate translation elongation in a well-characterized in vitro assay. PMID- 11198931 TI - Downregulation of the p75 neurotrophin receptor in tissue culture and in vivo, using beta-cyclodextrin-adamantane-oligonucleotide conjugates. AB - Formation of complexes with beta-cyclodextrin derivatives via adamantyl groups was found to enhance the uptake and antisense efficacy of phosphorothioate oligos targeted to the p75 neurotrophin receptor in neuronally differentiated PC12 cells. After a 2-week course of systemic administration to mice (by intraperitoneal injection), there was evidence of a pronounced uptake of these oligos by the dorsal root ganglia (DRG), as well as by liver and kidney. There was no uptake by the brain. Consistent with uptake of antisense oligos by the DRG, systemic administration resulted in marked and consistent downregulation of p75 in DRG neurons. These results indicate that cyclodextrin-adamantane-oligo conjugates have great potential as agents to downregulate target genes in neurons, particularly in vivo in the peripheral nervous system. PMID- 11198932 TI - A 5-year-old boy with failure to thrive and progressive neurological disabilities. PMID- 11198933 TI - Growth hormone therapy in Turner syndrome. PMID- 11198934 TI - Rational approach to the clinical protocol design for drug combinations: a review. AB - Based on the median-effect equation of Chou and the combination index (CI) equation of Chou-Talalay, a computer software for automated dose-effect analysis has been developed. This method provides quantitation of synergism (CI < 1) and antagonism (CI > 1) at different dose and effect levels. Therefore, it allows the selection of the best pair (or triplet) of combination, optimal combination ratio, and the best schedule of treatment. These analyses has been shown to be useful for the clinical protocol design. (Chang et al. Cancer Res. 45: 2434-2439, 1985). The user-friendly computer program also gives dose-reduction index (DRI) which determines how many fold of dose-reduction is allowed for each drug in synergistic combinations. Dose reduction leads to reduced toxicity while maintaining the desired efficacy (Chou et al. Encyclopedia of Human Biology 2:675 683, 1997; Encyclopedia of Cancer 1:368-379, 1997). The Chou-Talalay method distincts from all other methods by the fact that it not only takes into account the "potency" but also the "shape" of dose-effect curves of each drug and their combinations (Chou & Hayball, CalcuSyn for Windows, Biosoft, Cambridge UK, 1996). This method has been applied in combination of anticancer agents, anti-HIV agents, purging leukemic cells for autologous bone marrow transplantation (Chang et al. Cancer Res. 47:119-122, 1987) and combination of immunosuppressants for organs transplants. Specific examples of the theoretical equations, the median effect plot, the CI plot, the isobologram, and the polygonogram are illustrated. PMID- 11198935 TI - Genetic studies in acute lymphoblastic leukemia. AB - As the long-term event-free survival rate in children with acute lymphoblastic leukemia approaches 80%, emphasis is being placed on risk-directed therapy to prevent over- or undertreatment. It has become apparent that risk assignment based on primary genetic abnormalities is inadequate by itself, and that measurement of early responses to therapy and the extent of minimal residual disease is needed to improve the accuracy of risk classification. Studies to identify genetic polymorphisms with pharmacokinetic and pharmacodynamic significance promise to enhance the discovery of new drugs and to optimize chemotherapy. Recent successes in directing therapy to specific genetic abnormalities demonstrate the feasibility of molecular medicine for the childhood leukemias, and predict the development of highly effective drug regimens with minimal toxicity against normal hematopoietic cells. PMID- 11198936 TI - Mortality, morbidity, length and cost of hospitalization in very-low-birth-weight infants in the era of National Health Insurance in Taiwan: a medical center's experience. AB - The impact of implementation of the National Health Insurance on the outcome, cost, and length of hospitalization of very-low-birth-weight (VLBW) infants is not clear in Taiwan. These data are important for the planning of medical care and regionalization in this area. This study was an attempt to examine these questions. We retrospectively collected mortality, morbidity, and length and cost of hospitalization data of VLBW (BW < 1500 g) infants between March 1995 and February 1998. There were totally 162 patients enrolled. The overall mortality rate was 21.6%; the birth weight (BW)-specific mortality rate was 72%, 31%, 19%, and 3% for infants with BWs of < 750 g, 750-999 g, 1000-1249 g, and 1250-1499 g, respectively. The incidence of morbidities were: respiratory distress syndrome (74%), patent ductus arteriosus (36%), necrotizing enterocolitis (9%), sepsis (42%), intraventricular hemorrhage (15%), retinopathy of prematurity (31%), failure to pass auditory brainstem response (ABR) (34%), and chronic lung disease (17%). The average length of hospitalization was 67.2 days, and the cost per infant was 62 x 10(4) NT dollars; 108 +/- 38 days, 73 +/- 32 x 10(4) NT dollars if BW < 750 g; 94 +/- 15 days, 99 +/- 35 x 10(4) NT dollars if BW 750-999 g; 66 +/- 23 days, 64 +/- 36 x 10(4) NT dollars if BW 1000-1249 g; and 43 +/- 14 days, 39 +/- 37 x 10(4) NT dollars if BW 1250-1499 g. In conclusion, VLBW infants are associated with high mortality and morbidity rates. They have long lengths and high costs of hospitalization, and therefore deserve attention in the implementation of the National Health Insurance and regionalization. PMID- 11198937 TI - Partial liquid ventilation in normal rabbits: comparison of three kinds of perfluorocarbon. AB - Perfluorocarbon liquids have been used in liquid ventilation studies and considered an effective technique of gas exchange with less barotrauma when compared with gas ventilation. We compared the effects of partial liquid ventilation (PLV) using 3 kinds of perfluorocarbon liquids (Fluorinert FC 43, FC 77 and FC 84) available in Taiwan in normal rabbits. We were able to achieve adequate oxygenation and ventilation during a 2-hour-duration of PLV using FC 43, FC 77 or FC 84. There was no significant difference in hemodynamic status or laboratory findings between control group and PLV groups. There were also no significant differences before LV and after 2 hours of PLV among PLV groups. Histological study of lung tissue revealed intact and well expanded alveoli, and no significant pathological change after 2 hours of PLV. These results show that PLV using FC 43, FC 77 or FC 84 is an effective technique for maintaining adequate pulmonary gas exchange in normal rabbits. PMID- 11198938 TI - Bacterial infection in patients with transfusion-dependent beta-thalassemia in central Taiwan. AB - The microorganisms, outcome of infections and the risk factors were evaluated in 39 patients with beta-thalassemia who received frequent blood transfusions. Among these patients, thirteen developed 22 episodes of infections, and bacteremia accounted for 72.7% (16/22) of all infections. Three patients developed meningitis, two patients had liver abscesses, three patients had soft tissue infections, one patient had a urinary tract infection and one patient had lobar pneumonia. Interestingly, a large proportion of the patients were infected by Gram-negative bacteria. Patients who were implanted with intravascular catheters were most susceptible to bacterial infection (1.70 episodes/patient) (P = 0.0069). So were patients with ferritin levels over 2,000 ng/mL (1.18 episodes/patient) (P = 0.028). The frequency of bacterial infections in patients with splenectomies (1.08 episode/patient) was also significantly higher than that of the average patient (P = 0.025). In conclusion, three major risk factors for bacterial infection were identified in this group of patients: intravascular catheterization, high serum ferritin levels (> or = 2,000 ng/mL) and splenectomy. The infection rate of these patients (0.45 episode/100 patient-year) is about 20 fold higher than that of general pediatric patients (0.023 episode/100 patient year). PMID- 11198939 TI - Growth response and final height in Turner syndrome after combination therapy of growth hormone and anabolic steroid. AB - To improve the growth of Turner syndrome patients we administered human growth hormone (GH) combined with anabolic steroid. Thirty three patients completed at least one year of GH therapy. Daily GH injection was started at a dose of 1.0 IU/kg/wk at age 12.6 +/- 2.1 years when their heights were below -3.2 +/- 2.1 standard deviation, growth velocity was less than 4 cm/year and bone age (BA) was 9.9 +/- 1.7 years. Anabolic steroid was added at 14.3 +/- 1.3 years of age when their growth velocity slowed. Their consecutive annual growth velocities were: 7.40 cm/year; 6.15 cm/year; 5.47 cm/year; 4.74 cm/year and 4.05 cm/year respectively. Growth hormone therapy was discontinued when patients grew less than 4 cm/year, their BA reached 14 years or they were satisfied with their height. After combination therapy of GH for 3.0 +/- 1.1 years and anabolic steroids for 1.9 +/- 1.0 years, the final height of 17 patients was 150.3 +/- 4.1 cm. We compared our results with worldwide reports and analyzed demographic factors related to growth response and final height. We conclude that combination therapy of GH and anabolic steroid is effective in improving growth and final height of Chinese Turner patients. PMID- 11198940 TI - Ultrasound screening of neonatal adrenal hemorrhage. AB - Neonatal adrenal hemorrhage (NAH) is frequently overlooked because the majority of cases are asymptomatic. In this study, we investigated the clinical symptoms, echographic characteristics and incidence of NAH from January 1998 to December 1999 at Cathay General Hospital, Taipei, Taiwan. Among 3273 newborns who had ultrasound screening, 18 cases were diagnosed as having NAH. The incidence was 0.55% which was compatible with other reports. But there was a female predominance (10:8) which was different from previous reports. Only one premature baby was diagnosed with NAH. No patients had perinatal asphyxia, and this was different from other reports. The mean birth body weight was 3530 grams which was more than the 75th percentile of normal term baby birth weight. Sixteen cases had right-sided NAH and two cases had left-sided NAH. Eleven cases (61%) within this study were asymptomatic. The incidence of pathologic jaundice was 11%. Four babies (22%) had poor oral feeding combined with vomiting. Only one had severe anemia for which blood transfusion was required. There were no cases of adrenocortical insufficiency in our study. Only one patient received adrenalectomy. In conclusion, NAH can be detected early by sonography and most cases require only supportive treatment. Thus, unnecessary surgery and severe complications due to delayed diagnosis can be avoided. PMID- 11198941 TI - Common variable immunodeficiency with mosaic trisomy 8: report of one case. AB - This case study reported a 17-year-old female of common variable immunodeficiency (CVID) associated with bronchiectasis, pernicious anemia and mosaic trisomy 8. Clinically this patient presented with recurrent sinopulmonary infections, intractable diarrhea, macrocytic anemia, and primary amenorrhea. Immunological tests showed pan-hypogammaglobulinemia and a decrease of peripheral blood B cells (4%) and CD4+ cells (25%). Lymphoproliferative responses to mitogen (PHA) and specific antigen (BCG) were profoundly impaired in the patient in comparison to those in control. Production of interleukin 4 (IL-4) and gamma interferon (IFN gamma) in the in vitro lymphoproliferation was also profoundly depressed. Pernicious anemia demonstrated by larger MCV (112.9 fl) and hyper-segmental granulocytes on peripheral blood smear responded to parental administration of vitamin B12. Interestingly, she had a mosaic trisomy 8 in peripheral blood mononuclear cells but normal 46XX karyotype in the bone marrow cells. To our knowledge, this is the first case of CVID associated with mosaic trisomy 8 reported in the literature. As the case exemplifies, CVID should be considered when the physicians evaluate the patient presenting with recurrent sinopulmonary infections, diarrhea, malnutrition, and pernicious anemia. It requires further study to explore whether the genes in the chromosome 8 are linked to CVID. PMID- 11198942 TI - Hirschsprung's disease presenting with diffuse intestinal pneumatosis in a neonate. AB - In the neonate, pneumatosis intestinalis is almost always associated with necrotizing enterocolitis. The manifestation of diffuse intestinal pneumatosis in Hirschsprung's disease has been reported rarely. It may occur as a result of Hirschsprung's disease complicated with enterocolitis. We report a two-day-old female baby born at term with the problems of failure to pass meconium, progressive abdominal distension and bile stained vomiting. There was an early roentgenographic presentation of pneumatosis intestinalis which might have led to a diagnosis of necrotizing enterocolitis. However, the intestinal pneumatosis resolved within 48 hours. After anorectal manometry and contrast enema examination, an ileostomy was performed at the age of 23 days, and multiple biopsies of intestine showed aganglionosis up to the ileum at the level of 85 cm above the ileocecal valve. Unfortunately, the patient developed short bowel syndrome after operation and died suddenly after an accidental choking at the age of three months. This case suggests that Hirschsprung's disease may have an unusual early roentgenographic presentation with diffuse intestinal pneumatosis in the first few days of life. Anorectal manometries and suction biopsies are crucial for further diagnosis. PMID- 11198943 TI - Menetrier's disease associated with cytomegalovirus infection in a child. AB - Menetrier's disease is a rare disease with unknown etiology characterized by protein-losing hypertrophic gastropathy and hypoproteinemia. We report on a 4 year-old boy who presented with a 2-week history of vomiting and periorbital edema. Upper gastrointestinal endoscopy revealed prominent gastric rugae, while pathological examination showed hyperplastic mucosa with proliferation, elongation, and basal cystic dilatation of the gastric glands replaced by mucous secreting epithelium, confirming the diagnosis of Menetrier's disease. Virus isolation from urine revealed cytomegalovirus (CMV); and CMV immunoglobulin G and immunoglobulin M antibodies were detected in the serum. His condition gradually improved under omeprazole, with complete histological recovery after 3 months. PMID- 11198944 TI - Marketplace. California ruling means medical groups must be careful about disciplining docs. PMID- 11198945 TI - Perspectives. Taking back the BBA, 2001 edition: hello, telehealth; goodbye, UPL loophole. PMID- 11198946 TI - Serious adverse events attributed to nevirapine regimens for postexposure prophylaxis after HIV exposures--worldwide, 1997-2000. AB - In September 2000, two instances of life-threatening hepatotoxicity were reported in health-care workers taking nevirapine (NVP) for postexposure prophylaxis (PEP) after occupational human immunodeficiency virus (HIV) exposure. In one case, a 43 year-old female health-care worker required liver transplantation after developing fulminant hepatitis and end-stage hepatic failure while taking NVP, zidovudine, and lamivudine as PEP following a needlestick injury (1). In the second case, a 38-year-old male physician was hospitalized with life-threatening fulminant hepatitis while taking NVP, zidovudine, and lamivudine as PEP following a mucous membrane exposure. To characterize NVP-associated PEP toxicity, CDC and the Food and Drug Administration (FDA) reviewed MedWatch reports of serious adverse events in persons taking NVP for PEP received by FDA (Figure 1). This report summarizes the results of that analysis and indicates that healthy persons taking abbreviated 4-week NVP regimens for PEP are at risk for serious adverse events. Clinicians should use recommended PEP guidelines and dosing instructions to reduce the risk for serious adverse events. PMID- 11198947 TI - Nosocomial poisoning associated with emergency department treatment of organophosphate toxicity--Georgia, 2000. AB - Emergency department (ED) staff caring for patients contaminated with toxic chemicals are at risk for developing toxicity from secondary contamination. This report describes three cases of occupational illnesses associated with organophosphate toxicity caused by exposure to a contaminated patient and underscores the importance of using personal protection equipment (PPE) and establishing and following decontamination procedures in EDs and other areas of acute care hospitals. PMID- 11198948 TI - Special breast cancer stamp generates funds for novel studies. PMID- 11198949 TI - Dietary change and cancer prevention: what don't we know and when didn't we know it? PMID- 11198950 TI - Goals for nutrition in the year 2000. AB - Ongoing research continues to support the hypothesis that dietary factors significantly influence the incidence of many human malignancies. Despite some conflicting and confusing studies reported over the past two decades, it is becoming increasingly clear that maintenance of a healthy adult weight, through proper balance of caloric intake and physical activity, is key to cancer prevention. Moreover, current nutritional recommendations for the prevention of cancer include increased consumption of fruits and vegetables; reduced consumption of red meat and animal fat; and avoidance of excessive alcohol use. For many individuals, a daily multivitamin that contains folic acid may also be part of a reasonable overall cancer prevention strategy. PMID- 11198951 TI - What can randomized controlled trials tell us about nutrition and cancer prevention? AB - Randomized controlled trials are regarded as the most definitive of study designs. The randomized controlled trials that have tested nutritional factors for cancer prevention are reviewed. Trials that have tested the effects of nutrients given as high-dose supplements have been largely disappointing, typically showing either no or harmful effects. Possible benefits of vitamin E for prostate cancer prevention and selenium for prostate, colorectal, and lung cancer prevention have emerged only as secondary endpoints in trials conducted for other purposes; confirmatory new trials for these nutrients are now underway or are planned. The limitations of both past and current randomized controlled trials for studying diet-cancer relationships are discussed. The disappointing findings that have emerged from short-term studies of high-dose supplements cannot be interpreted as direct tests of the diet-cancer relationship because high-dose supplements cannot fully simulate the effects of whole foods on cancer risk. As we await findings from current and future trials, we should not forget that the ample evidence from observational epidemiologic research--suggesting that diets rich in fruits and vegetables can reduce the risk of many of the most common cancers--can provide a sound basis for nutritional recommendations aimed at reducing cancer risk. PMID- 11198952 TI - Evaluating complementary and alternative therapies for cancer patients. AB - "Complementary and alternative" therapies are actually a vast collection of disparate, unrelated regimens and products, ranging from adjunctive modalities that effectively enhance quality of life and promising antitumor herbal remedies now under investigation, to bogus therapies that claim to cure cancer and that harm not only directly, but also indirectly by encouraging patients to avoid or postpone effective cancer care. Complementary therapies such as music and massage, herbal teas to aid digestion and relieve nausea, yoga, tai chi, meditation, and the many other well-documented techniques that relieve stress and enhance well-being should be made available to patients to augment and ease the experience of cancer treatment and recovery. Many time-tested herbal and diet based remedies are now being studied for their abilities to induce or extend remission without toxicity. At the same time, lack of government regulatory authority leaves consumers at the mercy of those who promote unproved remedies, scores of which the grocery store and pharmacy shelves. Many of these over-the counter products contain harmful ingredients. Herb-drug interactions, only some of which are documented, occur with frequency and are sufficiently problematic to require that patients stop taking herbal remedies prior to surgery (to prevent interactions with anesthetics and anticoagulant effects); before radiation (due to potential for increased photosensitivity); and during courses of chemotherapy (to prevent product-drug interactions). Moreover, both good information and misinformation that appear in printed materials and on the Internet appeal to better educated consumers, who are, in fact, the most likely to try complementary and alternative methods. PMID- 11198953 TI - The challenge of prostate cancer. PMID- 11198954 TI - Prostate-specific antigen: current status. AB - Prostate-specific antigen (PSA) is the most important of all tumor markers in that it has significant applications in all aspects of the management of men with prostatic disease. Certainly, the most important utilization of PSA is for the early detection of this most ubiquitous of all human neoplasms. This article reviews the salient features of PSA, with particular emphasis on strategies to improve its utility in the diagnosis of prostate cancer. So-called PSA derivatives--including age-specific PSA, PSA velocity, and PSA density--are discussed. With the recognition of molecular forms of PSA, however, the ratio of free-to-total PSA, and now the complex form of PSA, have been shown to be more specific indicators of the presence of malignancy. Significant public interest and research efforts in prostate cancer have resulted in numerous advances over the past decade. The discovery of PSA and the development of assays to measure it will undoubtedly be recorded as one of the most important advances in the management of men with prostate cancer. PMID- 11198955 TI - Contemporary results of anatomic radical prostatectomy. AB - With current clinical practice, most newly diagnosed cases of prostate cancer are potentially life-threatening yet still curable. The anatomical (nerve-sparing) radical prostatectomy has dramatically improved the results of surgical treatment. Other new management options, including conformal (three-dimensional) external beam radiation therapy, radioactive seed implantation (brachytherapy), cryoablation, and hormonal therapy, may be useful in some patients, but they are all probably less effective than radical prostatectomy. Suitability for radical prostatectomy generally requires a clinically localized, potentially life threatening tumor [as defined by Gleason grade, tumor stage, and serum prostate specific antigen (PSA) level], a life expectancy of 10 years, and no serious co morbid medical conditions. With contemporary radical prostatectomy, about 70% of men with clinically localized disease will be cured, depending on tumor grade, tumor stage, and the serum PSA level. Urinary continence and sexual potency can be preserved in most patients, but substantially better results have been reported from centers of excellence than from community-based series. Other complications occur in about 10% of patients and with greater frequency in older patients. The operative mortality rate is less than 0.5%. Neoadjuvant hormonal therapy does not appear to affect treatment failure rates in patients undergoing radical prostatectomy. Prostatectomy may be beneficial in patients with microscopic lymph node metastases. Postoperative adjuvant radiotherapy may also be beneficial for patients with adverse pathologic findings. Salvage radical prostatectomy after radiation failure is associated with a 10-fold higher risk of complications and limited prospects for cure. Prospective, randomized clinical trials are underway to compare the results of radical prostatectomy with other treatments. Currently, radical prostatectomy is considered the preferred treatment for men with localized disease and a 10-year life expectancy. PMID- 11198957 TI - [An article for the Nederlands Tijdschrift voor Geneeskunde (Dutch Journal of Medicine)?]. AB - Original articles are the backbone of this journal, as with any scientific journal. The Nederlands Tijdschrift voor Geneeskunde stimulates submissions in this category of articles by offering an annual prize for young authors. On the other hand 30-40% of original articles has to be turned away by the editors, because of vital short-comings. The subject matter can be unsuitable, such as details about organisation of health care or a highly specialised topic. More often the methods are at fault. Common problems are: lack of a proper research question, result of medical or surgical treatment without a control group, use of a questionnaire, poor validity because of bias in selection of patients, circular reasoning in the assessment of a diagnostic test, or an inappropriate measure of outcome. We urge prospective authors to seek advice from a clinical epidemiologist or at least from a colleague with experience in clinical research before embarking on a clinical study. If such help is difficult to obtain the editors are prepared to act as intermediary between authors and methodological experts. PMID- 11198956 TI - Epithelial ovarian cancer: prevention, diagnosis, and treatment. AB - The leading cause of death from gynecologic malignancies in the United States is epithelial ovarian cancer. The significant risk factor for development of ovarian cancer is advancing age, although there is clearly a genetic predisposition- often associated with the BRCA1 and BRCA2 genes--in at least 5% to 10% of all epithelial ovarian cancers. Oral contraceptives are known to reduce the risk for development of ovarian cancer and should be considered as a method of birth control in women at increased risk. Currently, there is no acceptable method of screening for this disease, although measurement of CA-125 level and transvaginal ultrasound have been utilized. Ovarian cancer is a surgically staged disease. In apparent early-stage disease, complete surgical staging is critical for the selection of adjunctive therapy. In advanced-stage disease, the goal is primary cytoreduction. Standard postoperative therapy for advanced-stage ovarian cancer includes platinum-based chemotherapy with the substitution of paclitaxel for cyclophosphamide occurring in the last decade. Despite these advances in chemotherapy, ovarian cancer continues to be fatal in far too many cases. PMID- 11198958 TI - [Iron deficiency in premenopausal women and criteria for iron supplementation]. AB - Currently iron deficiency is treated only when anaemia has developed. In premenopausal women a haemoglobin level lower than 7.5 mmol/l justifies the diagnosis of anaemia. Reference values for haemoglobin in women have, however, been established while excluding only the extreme iron-deficient group, in which no iron could be found in the bone marrow. Studies on iron substitution in sufficient dosage in premenopausal women recorded haemoglobin values rising up to > or = 8.0 mmol/l. Premenopausal women will benefit from iron supplementation to optimize haemoglobin values and iron stores. Their physical condition is directly proportional to haemoglobin values. When pregnancy occurs sufficient iron stores corresponding to a ferritin value of > or = 80 micrograms/l are beneficial to mother and child. There are no rational arguments to refrain from iron supplementation in premenopausal women with suboptimal iron stores. PMID- 11198959 TI - [Importance of pharmacogenetics]. AB - Pharmacogenetics deals with the differences in effect of drugs caused by genetic variation. Differences can occur in therapeutic effect and in adverse events. Genetic variation in metabolism may result in high concentrations of drugs and an increased risk of adverse effects in slow metabolizers, which is important when using for example antidepressants or chemotherapy. Genetic variation also occurs in proteins interacting with drugs, which may change the effect of e.g. asthma drugs and antipsychotics. The selection of drugs and their dosages may be improved, and the number of adverse effects reduced by pharmacogenetic investigations. However, it may be important also in case of medical examinations for insurances and job appointments, since some patients may turn out to need expensive drugs or to be susceptible to a certain disease. Therefore, the use of genetic data in these instances has to be regulated. PMID- 11198960 TI - [Physical examination--measurement of muscle strength]. AB - Measuring muscle strength and establishing paretic symptoms are done first of all by having the patient perform actions or movements that require normal muscle strength. Measuring or grading the strength of separate muscle groups is usually done by means of the so-called Medical Research Council (MRC) scale that runs from 0 to 5, with the movement against gravity as an important criterion. This scale is not very valid in tract 4 (more strength than needed to overcome gravity, but still subnormal). Using a manual dynamometer or a fixed dynamometer it is possible to measure the strength of most clinically important muscle groups of the extremities and to compare them with values found in a normal population. For following the individual patient with a neuromuscular disorder, strength measurement with the dynamometer is more reliable than grading using the MRC scale. PMID- 11198961 TI - [Diagnostic image (19). Ecthyma gangraenosum]. AB - During chemotherapy for acute myeloid leukaemia a 30-year-old man developed skin lesions. Cultures from these lesions and of blood showed growth of Pseudomonas aeruginosa. The diagnosis was: ecthyma gangraenosum. Treatment with antibiotics and normalization of the granulocytes resulted in a complete recovery of the patient. PMID- 11198963 TI - [Original articles in the Netherlands Tijdschrift voor Geneeskunde in the second part of the 20th century: type of research described and the number and background of authors]. AB - OBJECTIVE: To determine the quantitative changes in methods and number of authors of original articles (OA) describing a (medical) scientific study in the Nederlands Tijdschrift voor Geneeskunde (NTvG) during 6 volumes in the second part of the 20th century. DESIGN: Retrospective bibliometric. METHOD: All OA published in 1949, 1959, 1969, 1979, 1989 and 1999 were screened on describing a (medical) scientific study, the method used, the number of authors, (medical) students or interns being part of the author list, the number of disciplines of the authors and the institutes where the authors did the study. RESULTS: The volumes mentioned contained 888 OA. The percentage of OA describing the used method increased from 47 in 1949 to 98 in 1999. In these OS 52% of the designs were retrospective. The proportion of prospective studies increased, but never met 25% of all OA. The median number of authors increased from 1 (range: 1-5) in 1949 to 5 (1-16) in 1999. The median number of disciplines of the authors increased from 1 (1-2) in 1949 to 3 (1-6) in 1999. The percentage of OA with students or interns being part of the author list varied from 1 in 1949 to 13 in 1999. In 1969-1999 most OA were received from authors from universities or academic hospitals. The percentage of OA received from authors from academic hospitals in collaboration with general hospitals increased from 0 in 1949 to 15 in 1999. Randomized clinical trials and prospective studies were mainly received from authors from universities or academic hospitals. The part of retrospective studies was largest among OA received from authors from general hospitals (58%). CONCLUSION: In the second part of the 20th century the OA published in the NTvG changed. The number of authors increased. In recent years most authors were from universities or academic hospitals, although the proportion written by authors from these institutes in collaboration with those from general hospitals increased. Most OA described retrospective studies, the proportion received from authors from general hospitals being the largest. The percentage of OA describing prospective studies increased over the years. PMID- 11198962 TI - [Limited effect of Health Council guideline on outpatient preoperative evaluation clinics in the Netherlands: an inventory]. AB - OBJECTIVE: To investigate the current status of preoperative evaluation in the Netherlands and the implementation of the Health Council recommendations. DESIGN: Cross-sectional study. METHOD: All Dutch anaesthesiologic partnerships and their hospital managers in February 2000 received a structured questionnaire about the existence of an outpatient evaluation clinic, possible problems in creating such a clinic and the contents of preoperative evaluation. RESULTS: We received responses of 101 (80%) and 111 (87%) from anaesthesiologists and managers, respectively. From 119 hospitals (94%) we received at least one useful questionnaire. On January 1, 2000, 24 (20%) hospitals had a complete and 36 (30%) a partial outpatient clinic. Within one year, 44% of the hospitals without a preoperative outpatient clinic expected to create one. The most common problem concerned financing this clinic. In hospitals with a complete clinic, anaesthesiologists were more often in employment (odds ratio (OR): 2.5; 95% confidence interval (95% CI): 1.0-10.0) and a routinely performed physical examination by the anaesthesiologist (or under his or her responsibility) was also conducted more often (OR: 5.0; 95% CI: 1.6-15.0). Not every patient saw an anaesthesiologist before entering the operating room in 70% of all hospitals. In hospitals without outpatient clinic, 57% of the day-surgery patients contacted the anaesthesiologist in the operating room. CONCLUSION: The recommendations of the Health Council of the Netherlands with respect to contents and organisation of the preoperative evaluation had, 3 years after being published, limited effect. PMID- 11198964 TI - [Loss of an eye due to hyper-IgE syndrome after corneal transplantation]. AB - A 37-year-old patient with bilateral keratoconus underwent a perforating cornea transplantation after acute onset of pain and hydrops of the right cornea. One day after operation endophthalmitis developed, caused by a viridans streptococcus. Hyper-IgE syndrome was suspected because of the patient's crude facial features. His medical history brought up additional symptoms of this disease. IgE levels were extremely elevated (7320 kU/l), the eosinophil count was slightly raised (0.25 x 10(9)/l). The patient was treated with several local antibiotics but his vision was only light perception at the time of discharge from the hospital. This case illustrates how an usually successful operation may have a disastrous outcome in case of late diagnosis of the hyper-IgE syndrome. The hyper-IgE syndrome can be recognized by the characteristic facial features in combination with the often extensive (juvenile) medical history with infections, and by elevated serum IgE levels. As patients with the hyper-IgE syndrome are extremely susceptible to develop infections, prophylactic antibiotic therapy is indicated in surgical procedures. PMID- 11198965 TI - [Research proposals submitted to the Dutch Investigative Medicine Fund; evaluation of the scientific quality by the Council for Scientific Research (NWO)]. AB - The Council for Medical and Health Research (MW-NWO) assessed the scientific quality of research proposals submitted to the Dutch Investigative Medicine Fund, and analysed if there had been changes over time in the proportion of proposals which the MW-NWO advised to reject, the role of reports of external reviewers and the most important methodological flaws. In the period 1995-1999 'reject' had been advised for an average of 50% of the proposals, with a tendency to a smaller proportion in recent years. In nearly half of the proposals the judgements of external reviewers were not in agreement with each other. There was only a weak correlation between the judgements of the reviewers and the final advice of NWO. Among the most important flaws mentioned in the NWO advice were: efficacy not proven (a prerequisite for the Fund), proposed study not needed to solve the policy problem and methodological flaws, e.g. design and power calculation not adequate, deficiencies of inclusion and exclusion criteria. PMID- 11198966 TI - [Mix-up of patient specimen: DNA-microsatellite analysis as a fast identification method]. AB - In a man aged 56 years with dysphagia, an oesophageal biopsy was found to contain an adenocarcinoma. In view of the discrepancy between the clinical and the histological pictures, the biopsy was repeated; in a second biopsy no carcinoma was demonstrable. DNA microsatellite analysis proved that the first biopsy originated from another person. The scheduled oesophageal resection was cancelled and the patient was reassured. A woman aged 77 years underwent gastrectomy because of biopsy samples with adenocarcinoma. However, no tumour was found in the resected stomach. DNA microsatellite analysis showed that the biopsy samples indeed originated from the patient. Unfortunately, mix-up of patient specimens occasionally occurs. Especially a discrepancy between the clinical picture and the histological diagnosis must raise the suspicion of a specimen mix-up. In such cases, DNA microsatellite analysis can give a rapid and reliable answer whether a mix-up has indeed taken place. PMID- 11198967 TI - [Summary of the guideline 'Sentinel Node Biopsy for Breast Cancer']. PMID- 11198968 TI - [Summary of the guideline 'Sentinel Lymph Node Biopsy for Breast Cancer']. PMID- 11198969 TI - [Summary of the guideline 'Sentinel Lymph Node Biopsy for Breast Cancer']. PMID- 11198970 TI - [Mix-up of patient specimens: error prevention through a systems approach]. AB - A correct diagnosis may reach the wrong patient because of a mix-up of either diagnostic specimens or identification data. It is astonishing how little attention is paid to this problem in medicine while the scale, the reach and the complexity of diagnosis are growing fast. More research is urgently needed to detect and investigate these types of errors. There is no quick remedy for this problem: a systems approach with comprehensive assessment of potential risks and subsequent management is the only sensible way out. Regrettably it is impossible to completely eliminate swapping errors, at best they can be reduced to an absolute minimum. PMID- 11199061 TI - Can the theory of planned behavior explain patterns of health behavior change? AB - This article tested the ability of the theory of planned behavior (TPB) to predict patterns of behavior change associated with health screening. Attitudes, subjective norms, perceived behavioral control, and intentions were used to predict objective measures of attendance 1 month and 13 months later among participants who had never previously been screened (N = 389). Findings showed that the TPB predicted attendance on each occasion and also predicted frequency of attendance. However, the model was unable to reliably distinguish among consistent attendees, participants who delayed attending, and participants who initially attended but relapsed. Thus, the TPB needs to be extended to understand behaviors that must be performed promptly and repeatedly for health benefits to accrue. PMID- 11199062 TI - Cognitive-behavioral stress management intervention decreases the prevalence of depression and enhances benefit finding among women under treatment for early stage breast cancer. AB - The authors tested effects of a 10-week group cognitive-behavioral stress management intervention among 100 women newly treated for Stage 0-II breast cancer. The intervention reduced prevalence of moderate depression (which remained relatively stable in the control condition) but did not affect other measures of emotional distress. The intervention also increased participants' reports that having breast cancer had made positive contributions to their lives, and it increased generalized optimism. Both remained significantly elevated at a 3-month follow-up of the intervention. Further analysis revealed that the intervention had its greatest impact on these 2 variables among women who were lowest in optimism at baseline. Discussion centers on the importance of examining positive responses to traumatic events--growth, appreciation of life, shift in priorities, and positive affect-as well as negative responses. PMID- 11199063 TI - Health locus of control in late life: a study of genetic and environmental influences in twins aged 80 years and older. AB - The factor structure of health locus of control (Form A; K. A. Wallston, B. S. Wallston, & R. DeVellis, 1978) was examined in 420 octogenarians (M age = 83.2 years), and the contributions of genetic and environmental factors to health control beliefs in 141 octogenarian twin pairs (71 identical, 70 same-sex fraternal) were estimated. Factor analyses reproduced previously proposed factors (Internal, Chance, and Powerful Others). Associations between health-control beliefs and life satisfaction, depression, and other health-related measures (e.g., self-rated health, outpatient contacts, and hospitalization), were modest. Quantitative genetic analyses revealed significant shared environmental influence on the Chance subscale, and significant familiality (attributable to a combination of genetic and shared environmental influences) on the Powerful Others subscale; there was no evidence of familiality on the Internal subscale. PMID- 11199064 TI - Associations between stress, trait negative affect, acute immune reactivity, and antibody response to hepatitis B injection in healthy young adults. AB - Eighty-four healthy graduate participants were administered the standard course of 3 hepatitis B vaccinations. Five months after the first dose (shortly after the second injection), each participant completed psychosocial measures, and a blood sample was drawn for determination of hepatitis B surface antibody titer. After completion of the vaccination series, participants performed an acute stress protocol, consisting of a 30-min adaptation period and a 5-min evaluative speech task. Blood was drawn at the end of the resting and task periods for assessment of cellular immune measures. Lower antibody response, as assessed after the second hepatitis B injection, was predicted independently by (a) high trait negative affect and (b) diminished T-cell proliferation in response to PHA. These data provide evidence that trait negative affect and the magnitude of stress-induced suppression of immune function may have clinical significance. PMID- 11199065 TI - An exploratory study of social support, distress, and life disruption among low income Hispanic women under treatment for early stage breast cancer. AB - Relationships between distress and perceived availability of social support were examined in 51 Hispanic women being treated for early stage breast cancer. Distress and different types (emotional, instrumental) and sources (spouse, women family members, other family members, friends) of support were measured at presurgery, postsurgery, and at 3-, 6-, and 12-month follow-ups. Emotional support from friends and instrumental support from spouse at presurgery predicted lower distress postsurgery. No other prospective benefits of perceived support emerged. Distress at several time points predicted erosion of subsequent support, particularly instrumental support from women in the family. In contrast to the adverse effects of distress (and independent of them), illness-related disruption of recreational and social activities at 6 months elicited greater support at 12 months. PMID- 11199066 TI - Psychological interventions and the immune system: a meta-analytic review and critique. AB - This article reviews evidence for the hypothesis that psychological interventions can modulate the immune response in humans and presents a series of models depicting the psychobiological pathways through which this might occur. Although more than 85 trials have been conducted, meta-analyses reveal only modest evidence that interventions can reliably alter immune parameters. The most consistent evidence emerges from hypnosis and conditioning trials. Disclosure and stress management show scattered evidence of success. Relaxation demonstrates little capacity to elicit immune change. Although these data provide only modest evidence of successful immune modulation, it would be premature to conclude that the immune system is unresponsive to psychological interventions. This literature has important conceptual and methodological issues that need to be resolved before any definitive conclusions can be reached. PMID- 11199067 TI - The effects of racial stressors and hostility on cardiovascular reactivity in African American and Caucasian men. AB - This study examined the effects of race-related stressors and hostility on cardiovascular reactivity in 31 African American and 31 Caucasian men. Participants viewed 3 film excerpts that depicted neutral, anger-provoking (but race-neutral), and racist situations. Participants exhibited significantly greater diastolic blood pressure reactivity to anger-provoking and racist stimuli compared with neutral stimuli. In addition, high hostility was associated with higher recovery systolic and diastolic blood pressure levels after exposure to the films. Although the results failed to confirm previous reports of greater reactivity to racism in African Americans, the findings suggest that diastolic blood pressure levels may remain elevated after exposure to racist stimuli. These results indicate that even indirect exposure to interpersonal conflict elicits significant reactivity, which can persist after exposure to the stressor, especially among high-hostile men. PMID- 11199068 TI - Persistent symptoms among survivors of Hodgkin's disease: an explanatory model based on classical conditioning. AB - Persistent symptoms of nausea, distress, and vomiting triggered by reminders of cancer treatment were examined among 273 Hodgkin's disease survivors, 1 to 20 years posttreatment. Prevalence rates were high for distress and nausea but low for vomiting. Retrospective report of anticipatory symptoms during treatment was the strongest predictor of persistent symptoms, suggesting that treatment-induced symptoms are less likely to persist if conditioning does not occur initially. Time since treatment was also a significant predictor, with patients more recently treated more likely to experience persistent symptoms. Thus, an explanatory model based on classical conditioning theory successfully predicted presence of persistent symptoms. Symptoms also were associated with ongoing psychological distress, suggesting that quality of life is diminished among survivors with persistent symptoms. Recommendations for prevention and treatment of symptoms are discussed. PMID- 11199069 TI - Statistical power of articles published in three health psychology-related journals. AB - Power was calculated for 8,266 statistical tests in 187 journal articles published in the 1997 volumes of Health Psychology (HP), Addictive Behaviors (AB), and the Journal of Studies on Alcohol (JSA). Power to detect small, medium, and large effects was .34. .74. and .92 for HP; .34, .75, and .90 for AB; and .41, .81. and .92 for JSA. Mean power estimates are .36, .77, and .91, giving a good estimation for the field of health psychology. J. Cohen (1988) recommended that power to detect effects should be approximately .80. Using this criterion, the articles in these journals have adequate power to detect medium and large effects. Intervention studies have much less power to detect effects than nonintervention studies do. Results are encouraging for this field, although studies examining small effects are still very much underpowered. This issue is important, because most intervention effects in health psychology are small. PMID- 11199070 TI - [Diagnosis of lethal poisoning with some substances used by toxicomaniacs]. AB - The authors analyze 62 expert conclusions on deaths from acute and chronic poisoning with various toxic substances used by toxicomaniacs. Forensic medical examination of corpses and forensic chemical analysis identified drugs, toluene, freon, organophosphorus compounds, and other toxins. PMID- 11199071 TI - [Regional forensic medical characteristics of sexual maturity]. AB - Published data on sexual maturity of women in the North are reviewed. The authors analyze the findings of their studies and the anthropometric parameters of sexual maturity recorded in Regulations of Forensic Medical Obstetrical and Gynecological Expert Evaluations (1966) and find essential differences in the values of some parameters as regards the population of the Russian European North. The authors propose revision of the current Regulations in order to define regional standards. PMID- 11199072 TI - [Morphology of hairs on the head and other parts of the body in the residents of Africa]. AB - The morphology of hairs from the head, beard, chest, armpits, and pubis was studied in indigenous population of Sudan, Sierra-Leone, Cote d'Ivoir, Ruanda, Nigeria, Gambia, Kenya, Uganda, Burundi, Zaire, Southern African Republic, Angola, Benin, and Guinea Bissau. A total of 327 hair specimens were examined. A number of new parameters of hairs were determined: thickness, number of cuticle pattern lines per mm, optic edge pattern, cuticle patterns, methods for detecting the cortical and medullar layers, width of hair layers and their transverse sections. The resultant morphological signs are new specific signs for African residents (Negroid) which can be used in forensic medical studies for identifying the race appurtenance of hairs. PMID- 11199073 TI - [Verification of amplified DNA profiles by electrophoresis in various gels]. AB - Differentiation of genotypical mixtures resultant from amplification analysis of mixed DNA preparations and false multi-strip profiles, which can result from amplification typing of individual DNA under certain conditions and simulate mixtures, impedes the molecular genetic identification expert evaluations. This paper offers an effective method for verification of amplification profiles of DNA, which is based on the use of alternative gel electrophoretic systems. This methodological approach helps detect the polymerase chain reaction artefacts without using additional expert material and promotes correct interpretation of expert findings even in difficult cases. PMID- 11199074 TI - [Immunochemical methods in detection of opiates in tissues and organs]. AB - Conditions of isolation of opiates from tissues and analysis of the resultant extracts by immunochemical methods are discussed. The main characteristics of OPIATES U kits (Pharmatech) for polarization fluorescent immunoanalysis of cadaveric material (liver) are determined. Immunochemical methods for forensic chemical analysis for opiates are experimentally compared. PMID- 11199075 TI - [Mechanism of sudden death in female pseudohermaphroditism]. AB - Sudden death in female pseudohermaphroditism is described. Hemorrhage into hyperplastic adrenals leads to acute adrenal failure and is the immediate cause of death. PMID- 11199076 TI - [Expert significance of evaluating volatile non-metal combustion products in analysis of blood from subjects dead in fire]. AB - Qualitative and quantitative composition and time course of formation of toxic substances during burning of polymers have been studied for two polymers, P-53-P and STBO. The most toxic gaseous products of nitrogen combustion are listed: hydrogen cyanide, nitrites, acid nitriles, aldehydes, aromatic carbohydrates, alkanes, and carbon oxide. Two expert conclusions are presented, including analysis of blood and viscera from subjects who died during fire. The following toxic substances were detected: carbon oxide, hydrogen cyanide, nitrites, acrylonitrile, acetonitrile, benzene, and methane in one case and the same products except carbon oxide in the other. The author considers that the list of tested toxic substances should be extended, particularly in cases with negative results of blood testing for carbon oxide and carboxyhemoglobin. PMID- 11199077 TI - [Antibodies in threshold dilutions of group-specific immune sera and their forensic medical significance]. AB - Antibodies of nonadsorbed antisera are specific and under certain conditions can react with nonhomologous antigens. This assumption is scientifically based and experimentally confirmed. This property of antibodies opens new vistas for solving theoretical and practical tasks in medicine and biology with regard to the antigen-antibody tests. A technology of making highly effective group specific immunoreagents for forensic medical institutions and blood transfusion service has been created. The technology of immunoreagent making is patented. PMID- 11199078 TI - [Forensic medical evaluation of injury outcome in a hemophilic patients]. PMID- 11199079 TI - [Detection of vaginal epithelial cells in a washing from a carrot]. PMID- 11199080 TI - [Validation of main notions of flaws in medical care]. AB - The authors define the notions of defects in medical care (DMC) in accordance with the new Criminal Code and Regulations for Estimating Harm to Health (Order No. 407 of Ministry of Health of the Russian Federation of December 10, 1996). Definitions of DMC, flaws in organization, diagnosis, and treatment, etc., at the prehospital and hospital stage of medical care are defined. List of the main components of DMC and their causes is presented. PMID- 11199082 TI - [Quality in forensic medical expert activities]. PMID- 11199081 TI - [Forensic medical diagnosis of chronic narcotic intoxication by morphological data]. PMID- 11199083 TI - [Forensic medical expert evaluation in connection with civil actions of patients complaining of improper dental care]. AB - The authors discuss questions facing forensic medical experts in connection with civil "medical" actions. The questions are classified as common and private. Expert evaluations of correspondence of the scope and quality of dental care are offered as the base for analysis of these problems within the framework of civil legislation. The data evidence efficiency of forensic medical expert evaluations in civil legal procedure and the significance of forensic medical service in the solution of problems of quality and efficiency of medical (including dental) care of the population. PMID- 11199084 TI - Perceived body image and eating behavior in young adults with cystic fibrosis and their healthy peers. AB - Treatment aimed at achieving an ideal nutritional status is an integral part of the management of patients with cystic fibrosis (CF). Emphasis is continually placed upon dietary intake and weight. The effects of this on eating behavior and self-perceptions are unclear. This work compared male and female CF adults with a healthy male and female control population with regard to (a) clinical variables, (b) actual, perceived, and desired body shape/body mass index (BMI), and (c) body satisfaction, eating behaviors and attitudes, and self-esteem. Clinical data were recorded for 221 adults with CF and 148 healthy controls. All subjects completed BMI Charts (perception of body weight/BMI), the Eating Attitudes Test, and scales of body satisfaction and self-esteem. CF patients had poorer lung function and nutritional status than controls. Control males accurately perceived their body shape/BMI and were content with it, whereas CF males viewed their BMI as greater than it actually was and desired to be much heavier. Control females viewed their body shape/BMI as less than it actually was and desired to be even slimmer, in comparison with CF females, who perceived their BMI as less than it actually was but were happy with their perceived shape/weight. Control subjects, especially females, dieted to a greater extent and were more preoccupied with food (with binge eating and intended vomiting) than CF patients. Conversely, those with CF reported greater pressure from others to eat than did controls. More problems with food/eating behavior were associated with less body satisfaction and reduced self-esteem. In comparison with a healthy control population, the perceptions and behaviors of CF adults relating to eating, weight, and body image are not abnormal. Indeed, females with CF have fewer problems than their healthy peers. PMID- 11199085 TI - Serum cholesterol concentrations and mood states in violent psychiatric patients: an experience sampling study. AB - The well-documented negative association between serum cholesterol and aggressive behavior has led Kaplan to propose a cholesterol-serotonin hypothesis of aggression. According to this hypothesis, low dietary cholesterol intake leads to depressed central serotonergic activity, which itself has been reported in numerous studies of violent individuals. In the present study, 25 violent psychiatric patients participated in a microbehavioral experience sampling procedure to examine differences in self-reports of affective and cognitive experiences as a function of serum cholesterol concentrations. For 7 days, they wore signaling devices that emitted an average of seven signals a day. Following each signal, patients filled out a mood questionnaire. Total serum cholesterol (TSC) concentration was positively associated with measures of affect, cognitive efficiency, activation, and sociability, suggesting a link between low TSC and dysphoria. These findings are consistent with the cholesterol-serotonin hypothesis and with the substantive literature linking both aggression and depression to depressed central serotonergic activity. PMID- 11199086 TI - DNA repair capacity in healthy medical students during and after exam stress. AB - There has been extensive research into the effects of stress on immune function but little on the effects of stress on DNA repair capacity (DRC), a process central to maintaining a normal cell cycle. Defective DRC is one of the factors responsible for carcinogenesis. In the present study we assessed DRC in healthy medical students during times of high and low stress. Sixteen medical students were evaluated during the third day of a 5-day exam period and then again 3 weeks later, after vacation. At both time points, participants underwent a brief physical examination, had venous blood drawn, and completed questionnaires to identify subjective stress levels. The DRC was assessed by the host-cell reaction assay, which measures nucleotide excision repair capacity. Participants reported significantly higher levels of subjective stress during the exam period than after vacation. DRC was also significantly higher during the exam period than after vacation, suggesting a positive association between subject stress levels and DRC. The results are discussed in relation to previous findings and implications for cancer research. PMID- 11199087 TI - Sex, drugs, and HIV: does methadone maintenance reduce drug use and risky sexual behavior? AB - This study examined differences in drug use, sexual behavior, attitudes, and perceptions of vulnerability for AIDS between injection drug users who received methadone treatment in the previous 6 months and those who did not. Of the 123 participants assessed, 62 (50%) received methadone treatment. Methadone patients reported fewer sexual partners and greater use of condoms compared to nonmethadone patients. Methadone patients also reported fewer high-risk sexual partners than those not in treatment. Women reported more high-risk partners than men. Methadone patients reported drinking alcohol less, but smoking marijuana more than nonmethadone users. Methadone users had more positive beliefs about the efficacy of condoms for preventing AIDS and expressed less anger than nonmethadone users in situations related to condom usage. These findings have important implications for using methadone maintenance to reduce the dual risk for HIV in injection drug users. PMID- 11199088 TI - A social-ecologic approach to assessing support for disease self-management: the Chronic Illness Resources Survey. AB - We report on the development and validation of an instrument to assess support and resources for chronic illness management (the Chronic Illness Resources Survey; CIRS). The 64-item full instrument and the 29-item Brief CIRS are based on a social-ecologic model, designed to apply across chronic diseases, and assess support and resources at each of seven levels (e.g., family and friends, physician and health care team, neighborhood/community). A prospective evaluation with 123 patients having heart disease, arthritis, diabetes, and/or COPD revealed that the overall instrument, as well as subscales and the brief instrument, had acceptable internal consistency, moderate to high test-retest reliability, good construct validity, and moderate concurrent and prospective criterion validity. We discuss potential uses of the CIRS for assessment, feedback, tailoring intervention, and evaluation and make recommendations for future research. PMID- 11199089 TI - Verifying drug abuse prevention program effects using reciprocal best friend reports. AB - Considerable research suggests that social influences-based drug abuse prevention programming has produced the most consistently successful preventive effects. However, a common criticism of this literature is that most prevention intervention studies rely solely on self-reported substance use. The purpose of this study was to assess the effects of normative education, arguably the most successful component of social influence based prevention programs, on alcohol and cigarette consumption using both self- and reciprocal best friend reports of substance use. Analyses of subsamples of data from 11,995 students participating in the Adolescent Alcohol Prevention Trial revealed that normative education significantly delayed the onset of alcohol use across the eighth, ninth, and tenth grades among public school students. A similar but somewhat less robust pattern was found for cigarette use. These results suggest that self-report bias does not account for previous findings and demonstrate rather convincingly that normative education is an effective drug prevention strategy for public school settings. PMID- 11199091 TI - Epithelial cells and fibroblasts. AB - Chronic obstructive pulmonary disease (COPD) is characterized by acute and chronic alterations in the cellular composition structure of the airways and alveoli. Much attention has been focused on the increase in inflammatory cells present both within the airway lumen and within the airway wall. The parenchymal cells of the airway are intimately involved in the recruitment and activation of these inflammatory cells. Conversely, the behaviour of parenchymal cells can be modulated by inflammatory cells. The parenchymal cells can also alter the structural elements present within the airway leading to architecture changes which can impair lung function. Finally, epithelial cells and fibroblasts can directly modify each other's behaviour. The activity of these cells, therefore, undoubtedly can play a variety of roles in the pathophysiologic processes which underlie COPD. PMID- 11199092 TI - Macrophage control of inflammation: negative pathways of regulation of inflammatory cytokines. AB - The recruitment of leukocytes from the blood compartment constitutes a multistep process which involves primary and secondary inflammatory cytokines, as well as adhesion molecules expressed on leukocytes and endothelial cells. The properties of the interleukin (IL)-1 system and of chemokines, as well as their interplay, are analysed. These mediators offer new paradigms to understand diverse pathologies, and provide tools and targets for the development of novel therapeutic strategies. PMID- 11199093 TI - Neutrophils in chronic obstructive pulmonary disease. AB - Neutrophil accumulation in the lung is a prominent feature of chronic obstructive pulmonary disease (COPD) and the activation of these cells, producing proteases and oxygen-derived free radicals, is thought to be important in the pathogenesis of the disease. An important step in recruitment is the local generation of a neutrophil chemoattractant signal which mediates the trapping and firm adhesion of rolling neutrophils on the microvascular endothelium, followed by migration via intercellular junctions. Two neutrophil chemoattractants are particularly important in this respect, C5a generated by cleavage of complement C5 in interstitial fluid, and interleukin (IL)-8 synthesized by cells in the lung, e.g. macrophages, epithelial cells, endothelial cells, smooth muscle cells and neutrophils themselves. Lipid mediators, such as leukotriene B4 (LTB4), are also potentially important. Several studies have been carried out to investigate the role of IL-8 in COPD. IL-8 has been detected in bronchoalveolar lavage fluid and sputum from such subjects and in the systemic circulation. The levels of IL-8 have been found to correlate with neutrophil numbers and markers of neutrophil activation, such as myeloperoxidase activity. Some studies have also found a correlation between IL-8 levels, neutrophil numbers and the degree of lung dysfunction. These parameters are insensitive to steroids. Thus, the mechanisms involved in neutrophil recruitment, i.e. chemoattractant secretion or action, adhesion and endothelial transmigration, are important potential targets for the development of novel therapy. The IL-8 receptors on neutrophils, CXCR1 and CXCR2, are of particular interest. PMID- 11199094 TI - Lymphocytes, chronic bronchitis and chronic obstructive pulmonary disease. AB - Chronic obstructive pulmonary disease (COPD) is a cytotoxic T lymphocyte (CD8)- and macrophage (CD68)-predominant chronic inflammatory disorder of the conducting airways and alveoli. This is often associated with a neutrophilia, inflammation of small airways and destruction of tissue beyond the terminal bronchiolus, i.e. emphysema. In contrast, asthma is a helper T cell (CD4; type 2)-predominant chronic inflammatory disorder of the conducting airways in which there is T lymphocyte-derived gene expression for interleukin (IL)-4 and IL-5 but not interferon gamma. There is fragility of airway surface epithelium, thickening of the reticular basement membrane, bronchial vessel congestion and (when severe) an increase in the mass of bronchial smooth muscle. This is usually (but not always) associated with tissue and peripheral blood eosinophilia rather than a neutrophilia and there is exudative plugging of the airways. These differences of inflammatory profile, remodelling and lung function are seen when smokers with COPD are compared with non-smoking mild asthmatics. However there may be important similarities and overlap, particularly in more severe asthma when neutrophils predominate and in the older and or smoking asthmatic when reversibility of airflow is less obvious. We have recently demonstrated gene expression for IL-4 and IL-5 in and around the mucus-secreting glands of airways resected from smokers without a history of asthma. Also exacerbations of bronchitis may be associated with a tissue eosinophilia. On examination of bronchial biopsies from these patients we show surprisingly strong gene expression for IL-4, IL-5 and even human eotaxin and RANTES (regulated on activation normal T cell expressed and secreted). Whilst CD4 T lymphocytes of the Th2 phenotype might be expressing these cytokines in bronchitis, CD8 T lymphocytes are also capable of secreting IL-4 and IL-5. Viruses may modulate these changes in distinct lymphocyte functional phenotypes. The relevance and importance of CD4/CD8 T lymphocyte ratio to the development of COPD is discussed. PMID- 11199095 TI - Oxidants/antioxidants and chronic obstructive pulmonary disease: pathogenesis to therapy. AB - There is now considerable evidence for an increased oxidant burden in smokers, particularly in those smokers who develop chronic obstructive pulmonary disease (COPD), as shown by increased markers of oxidative stress in the airspaces, breath, blood and urine. The presence of increased oxidative stress is a critical feature in the pathogenesis of COPD, since it results in inactivation of antiproteinases, airspace epithelial injury, mucus hypersecretion, increased sequestration of neutrophils in the pulmonary microvasculature, and gene expression of pro-inflammatory mediators. The sources of the increased oxidative stress in patients with COPD derive from the increased burden of oxidants present in cigarette smoke, or from the increased amounts of reactive oxygen species released from leukocytes, both in the airspaces and in the blood. Antioxidant depletion or deficiency in antioxidants also contributes to oxidative stress. The development of airflow limitation is related to dietary deficiency of antioxidants and hence dietary supplementation may be a beneficial therapeutic intervention in this condition. Oxidative stress also has a role in enhancing the airspace inflammation, which occurs in smokers and patients with COPD through the activation of redox-sensitive transcriptions factors such as NF-kappa B and AP-1, which regulate the genes for pro-inflammatory mediators and protective antioxidant gene expression. Antioxidants that have good bioavailability or molecules that have antioxidant enzyme activity are therefore therapies that not only protect against the direct injurious effects of oxidants, but also may fundamentally alter the inflammatory events which have a central role in the pathogenesis of COPD. PMID- 11199096 TI - Proteases and antiproteases. AB - Serine proteases have been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD) since the identification of alpha 1-antitrypsin deficiency in 1963. This inhibitor efficiently inactivates several enzymes released by activated neutrophils including neutrophil elastase, cathepsin G and proteinase 3, all of which have been shown to generate features of COPD in animal models. Recent studies have identified the mechanisms of enzyme release from activated neutrophils and indicate that the concentrations are usually two orders of magnitude above that of normal alpha 1-antitrypsin. This results in an area of obligate proteolysis in the immediate vicinity of a migrating neutrophil. The area is greatly enlarged in alpha 1-antitrypsin deficiency explaining the increased susceptibility of such patients to develop lung damage. The migration into and activation of neutrophils in the lung is likely to be a major determinant of the development of COPD. Understanding the processes has important implications for the design of new therapeutic strategies. PMID- 11199097 TI - Matrix metalloproteinases and TIMPs: properties and implications for the treatment of chronic obstructive pulmonary disease. AB - The matrix metalloproteinases (MMPs) are a unique family of metalloenzymes that, once activated, can destroy connective tissue. The active enzymes are all inhibited by tissue inhibitors of metalloproteinases (TIMPs). The relative amounts of active MMPs and TIMPs are important in determining whether tissues are broken down in disease. Although elastase is often regarded as the target enzyme in chronic obstructive pulmonary disease (COPD), both the neutrophils and macrophages in the lung contain metalloproteinases and both collagen and elastin are degraded in disease. Transgenic studies have shown that when MMP1 is over expressed, pulmonary emphysema develops in mice, while MMP12 knockout mice do not develop pulmonary emphysema when exposed to cigarette smoke. New drugs that can specifically block active MMPs are now available. These potent inhibitors are effective in vitro and prevent the destruction of tissue in animal models. Future patient trials will test the effectiveness of these compounds in preventing tissue destruction. PMID- 11199098 TI - Pulmonary alveolus formation: critical period, retinoid regulation and plasticity. AB - Pulmonary alveoli, the lung's gas-exchange structures, are formed in part by subdivision (septation) of the saccules that constitute the gas-exchange region of the immature lung. Although little is known about the regulation of septation, relatively recent studies show: (1) all-trans retinoic acid (RA) treatment of newborn rats increases septation and prevents the inhibition of septation produced by treatment of newborn rats with dexamethasone, a glucocorticosteroid hormone; (2) treatment with RA of adult rats that have elastase-induced emphysema increases lung elastic recoil, induces the formation of alveoli, and increases volume-corrected alveolar surface area; and (3) in tight-skin mice, which have a genetic failure of septation, and in rats in which septation had previously been prevented by treatment with dexamethasone, treatment with RA partially rescues the failed septation. These findings raise the possibility that treatment with RA will induce the formation of alveoli in humans with pulmonary emphysema. PMID- 11199099 TI - Systemic effects of chronic obstructive pulmonary disease. AB - Traditionally, chronic obstructive pulmonary disease (COPD) has been understood as a disease of the lungs, characterized by irreversible airflow limitation due to chronic bronchitis and/or emphysema. The latter are thought mainly to be the consequence of an excessive inflammatory response to tobacco smoking. Recently, several studies have shown that this pulmonary inflammation may also be detected in the systemic circulation, and that this systemic inflammation may have important clinical consequences. Most prominent among them is the loss of skeletal muscle mass that a significant percentage of patients with COPD will show during the course of their disease. This limits considerably their exercise capacity, jeopardizes their health status, and has a negative impact on their prognosis. Importantly, such prognostic value is independent of the degree of airflow obstruction and potentially reversible with appropriate therapy. This chapter summarizes available evidence supporting the concept that COPD is more than a lung disease (the systemic effects of COPD), and speculates on potential cellular mechanisms as future therapeutic targets. PMID- 11199100 TI - Potential novel therapies for chronic obstructive pulmonary disease. AB - While considerable progress has been made in development of drugs for asthma, there have been few advances in the treatment of chronic obstructive pulmonary disease (COPD). New therapeutic approaches to prevent disease progression are urgently needed and these will arise out of better understanding of the disease process at a cell and molecular level. The inflammatory response in COPD differs markedly from that of asthma, with differences in inflammatory cells, mediators and response to therapy. The neutrophilic inflammation is orchestrated by chemotactic factors, such as interleukin (IL)-8, other CXC chemokines and leukotriene B4; receptor blockers (CXCR1, CXCR2, BLT antagonists) or synthesis inhibitors (5'-lipoxygenase inhibitors) might be effective. Tumour necrosis factor (TNF) alpha may be an important amplifying cytokine and there are several strategies for blocking it (antibodies, soluble receptors, TACE inhibitors). IL 10 is effective in blocking the synthesis of IL-8 and TNF alpha as well as proteases. Oxidative stress and peroxynitrite may be important in COPD; more effective antioxidants are now in development. The inflammatory response in COPD is essentially steroid-resistant so that alternative anti-inflammatory treatments are needed. Phosphodiesterase 4 inhibitors look promising in early clinical studies. Nuclear factor-kappa B inhibitors and p38 MAP kinase inhibitors may also be effective. Several protease inhibitors are in development including those for neutrophil elastase, selective matrix metalloproteinase and cathepsin. PMID- 11199101 TI - Overview of current therapies. AB - The therapy of chronic obstructive pulmonary disease has been comprehensively reviewed in a number of international treatment guidelines. There is consensus about what elements should be included, but the purposes of therapy and the timing of its introduction remain poorly defined. Major factors limiting effective treatment beyond those associated with the biology of the condition itself are poor diagnostic methodology, failure to identify relevant co morbidities and reluctance to devote appropriate resources to maximizing patient gain. Too many patients are identified at the end-stages of their illness when treatment is relatively limited. Most therapy is directed at reducing the impact of the disease in terms of symptoms, exercise performance and exacerbations on the individual and only smoking cessation modifies the evolution of the disease. Treatment of hypoxaemic patients with domiciliary oxygen improves mortality and slows the development of pulmonary hypertension. Effective smoking cessation is relevant at all stages of the disease. It depends on the willingness of the individual to participate, and quit rates can be improved by the use of nicotine replacement therapy and possibly bupropion. Inhaled bronchodilator drugs palliate symptoms and improve exercise performance in pharmacologically predictable ways. In patients with severe disease, reduction in operating lung volumes is more important than 'bronchodilitation' and is better sustained by long acting beta agonists and anticholinergics. Inhaled corticosteroids reduce exacerbation rates and improve health status in established disease but do not modify disease evolution. Pulmonary rehabilitation improves exercise performance and health status without changing underlying pulmonary mechanics. Whether hospitalizations and exacerbations can be modified is still to be established. Nutritional therapy is in its infancy but calorie supplementation alone is insufficient to improve patient well being. Selected individuals can undergo lung volume reduction surgery with benefits extending up to two years but the risks are dependent on the skill of the operators and the appropriateness of patient selection. Lung transplantation is symptomatically helpful but does not modify the natural history of the disease. Hospitalization due to exacerbations of disease is frequent and their treatment with bronchodilators, antibiotics and corticosteroids now have a basis in randomized trial data. Mortality reflects the incidence of respiratory acidosis and noninvasive ventilation has a role in safely managing patients outside of the intensive care unit. Effective prevention of exacerbation should be possible with newer antiviral agents but data are presently lacking. PMID- 11199102 TI - Chronic obstructive pulmonary disease: an overview of pathology and pathogenesis. AB - A cigarette smoke-induced inflammatory process underlies the pathogenesis of the majority of pathologic lesions associated with chronic obstructive pulmonary disease (COPD). In chronic bronchitis, this process is located in the mucosa, gland ducts and glands of intermediate sized bronchi with an internal diameter of 2-4 mm. The mucus-containing exudate produced by the inflammatory response overpowers the normal clearance mechanisms, resulting in the cough and expectoration that characterize chronic bronchitis. In some cases of chronic bronchitis, the inflammatory process extends to smaller bronchi and bronchioles less than 2 mm in internal diameter. In this location, the inflammatory process thickens the wall, narrows the lumen and destroys the parenchymal support of the airways. These changes progressively increase peripheral airways resistance and eventually reduce the patient's ability to empty their lungs to a degree that can be measured by a reduction in FEV1 (forced expiratory volume in one second). The reduction in lung surface area produced by parenchymal inflammation contributes to the decline in FEV1 by reducing lung elastic recoil, which is the major force driving air out of the lung. It also contributes to the reduction in diffusing capacity by reducing the lung capillary bed. The purpose of this presentation is to review the quantitative aspects of these pathological changes and attempt to provide insight into factors which result in progression of these lesions. PMID- 11199103 TI - Genetics of chronic obstructive pulmonary disease. AB - The marked variability in the development of chronic obstructive pulmonary disease (COPD) in response to cigarette smoking has been known for decades, but severe alpha 1-antitrypsin deficiency (PI Z) remains the only proven genetic risk factor for COPD. With cigarette smoking, PI Z subjects tend to develop more severe pulmonary impairment at an earlier age than non-smoking PI Z individuals. However, PI Z individuals exhibit wide variability in pulmonary function impairment, even among individuals with similar smoking histories. Therefore, other genes and environmental exposures are also likely involved. The role of heterozygosity for the Z allele as a risk factor for COPD remains controversial, but accumulating evidence suggests that at least some PI MZ individuals are at increased risk of developing airflow obstruction. In individuals without alpha 1 antitrypsin deficiency, familial aggregation of COPD has been reported in several studies. To study novel genetic determinants of COPD, our research group enrolled 44 severe, early-onset COPD probands (FEV1 < 40%, age < 53 yrs, non-PI Z) and 266 of their relatives. A marked female predominance was noted among the early-onset COPD probands. In addition, increased risk to current or ex-smoking first-degree relatives of early-onset COPD probands for reduced FEV1, chronic bronchitis and spirometric bronchodilator responsiveness has been demonstrated. These data strongly support the genetic basis for the development of COPD and the potential for gene-by-environment interaction. A variety of studies have examined candidate gene loci with association studies, comparing the distribution of variants in genes hypothesized to be involved in the development of COPD in COPD patients and control subjects. For most genetic loci which have been tested, there have been inconsistent results. Genetic heterogeneity could contribute to difficulty in replicating associations between studies. In addition, case-control association studies are susceptible to supporting associations based purely on population stratification, which can result from incomplete matching between cases and controls--including differences in ethnicity. No association studies in COPD have been reported which used family-based controls, a study design which is immune to such population stratification effects. More importantly, no linkage studies have been published in COPD to identify regions of the genome which are likely to contain COPD susceptibility genes--regions in which association studies are likely to be more productive. PMID- 11199104 TI - Mucus hypersecretion in chronic obstructive pulmonary disease. AB - Most patients with chronic obstructive pulmonary disease (COPD) exhibit characteristics of airway mucus hypersecretion, namely sputum production, increased luminal mucus, submucosal gland hypertrophy and goblet cell hyperplasia. The clinical consequences of hypersecretion are impaired gas exchange and compromised mucociliary clearance, which encourages bacterial colonization and associated exacerbations. However, the extent of the contribution of mucus to pathophysiology of COPD is controversial. Early epidemiological studies found little evidence for the involvement of mucus in the age-related decline in lung function and mortality associated with COPD and concluded that chronic airflow obstruction and mucus hypersecretion were independent processes. Later studies found positive associations between phlegm production and decline in lung function, hospitalization and death. Thus, although not diagnostic for the condition, mucus hypersecretion contributes to morbidity and mortality in certain groups of patients with COPD. This suggests that it is important to develop drugs that inhibit mucus hypersecretion in these patients. Unfortunately, ambiguity in clinical studies of mucoactive drugs means that mucolytics are not recommended in clinical management. Future research should determine whether there is an intrinsic abnormality in mucus in COPD, which will determine development of appropriate inhibitors, which in turn can be used in 'proof of concept' and in treatment. PMID- 11199105 TI - Mechanisms of exacerbations. AB - Exacerbations of chronic obstructive pulmonary disease (COPD) are a major cause of morbidity and mortality and hospital admission. Some patients are particularly susceptible to develop frequent exacerbations; exacerbation frequency being an important determinant of health related quality of life. Patients with frequent exacerbations (three or more exacerbations per year) have increased induced sputum cytokine interleukin (IL)-6 and IL-8 levels when stable, suggesting that frequent exacerbation is associated with increased airway inflammatory changes. Respiratory viral infections are a major cause of COPD exacerbations, with upper respiratory tract infections (colds) being associated with two-thirds of COPD exacerbations. Rhinovirus has been detected in induced sputum by PCR in 25% of exacerbations, suggesting that rhinovirus may directly infect the lower airway triggering exacerbation. The presence of an upper respiratory tract infection leads to a longer symptom recovery time at exacerbation. At exacerbation induced sputum IL-6 levels were increased compared to stable, though there were no significant increases in IL-8 or sputum cell counts. Sputum IL-6 levels were found to be higher in those patients with symptoms of a common cold. Increased airway eosinophilia has been also found at exacerbation. Other factors including bacterial colonization of the airways, temperature and interactions with environmental pollutants may also play a role in COPD exacerbation. PMID- 11199106 TI - [Writing process, PPmP and I in the middle of the word]. PMID- 11199107 TI - [Differences in 2 diagnostic groups of psychosomatic patients on the Symptom Checklist 90-R (SCL-90-R). Consequences for using SCL-90-R in follow-up research]. AB - 680 unselected outpatients of our Psychosomatic Clinic were divided into six diagnostic groups and examined by the SCL-90-R. By ANOVA we found differences of means between the diagnostic groups for the global severity score (GSI) and for the subscale scores. We describe the model of Jacobson et al. [1,2] for the determination of cut-off-points and reliable change indices for the assessment of changes over time, e.g. after psychotherapy. Our results lead to the conclusion that, although an overall reliable change index for the GSI can be applied to all psychosomatic patients, cut-off-points should be different following the diagnostic groups. Furthermore, information from the SCL-90-R-subscales as well as other specific symptom scales should be used for the interpretation of significant changes of the GSI. PMID- 11199108 TI - [Axis I "illness experience and treatment preconditions" of operational psychodynamic diagnosis (OPD). Experiences in clinical practice]. AB - In a selective survey, results on psychometric properties and aspects of application of the axis I, "illness experience and treatment preconditions" of the Operational Psychodynamic Diagnoses (OPD) are described. Following remarks on the role of defense and coping theories in the conceptualisation of the axis, its structure and contents are outlined. After a brief summary of findings on its interrater reliability, several aspects of validity are discussed. Results on discriminative validity show that axis I items are useful in the statistical discrimination of subsamples differing in age, clinical diagnoses, and diagnostic setting (psychotherapy outpatient vs. psychosomatic consultation-liasion services). The contribution of axis I items to prediction of treatment outcomes, moreover, reveals high degree of predictive or treatment validity. After an integrative discussion of these findings, implications of patient personality and coping behaviour for axis I ratings are highlighted as important objectives for future OPD research. PMID- 11199109 TI - [Retinopathia centralis serosa--stomach ulcer of ophthalmology?]. AB - Centralis serosa retinopathy is regarded in ophthalmology as a psychosomatic disease, although this assumption has not been satisfactorily proven so far. With the use of the Freiburg Personality Inventory (FIP, [4]), the questionnaire for the evaluation of psychosomatic pathological processes [10], and by recording the affliction undergone by stressful events in the patients' lives, the question as to whether a psychogenic contributory cause existed was examined with a control group study (n = 11), parallelised according to age and sex. The results proved significantly that there was a psychosomatic connection, specifically a tendency to somatisation in patients with centralis serosa retinopathy. However, it was not possible to compile a typical personality profile, although it was possible to describe some conspicuous personality features. As a conclusion, the consequences for a subsequent study are being discussed. PMID- 11199110 TI - [Method of plan formulation: first German language rehabilitation study of the Joseph Weiss "control mastery theory"]. AB - The paper gives a survey of the "Control Mastery Theory" (CMT) of Joseph Weiss. CMT is a cognitive-affective, psychoanalytic theory of the psychotherapeutic process. The San Francisco Psychotherapy Research Group empirically investigated und confirmed several concepts of the CMT. Some research results are summarized and the "Plan Formulation Method" is described in detail. The results of the first German reliability study applying the plan formulation method on the case "Amalie" show that the method can be used reliably for research purposes outside the USA. PMID- 11199111 TI - [The Antonovsky Sense of Coherence Scale. Test statistical evaluation of a representative population sample and construction of a brief scale]. AB - In this article we will describe the evaluation of Antonovsky's 29-items Sense of Coherence Scale (SOC-29) in a large community sample (n = 2.005) of the German population and the development of the Leipzig Short Scale (SOC-L9), which consists of only 9 items. The SOC-29 has a high internal consistency (alpha = 0.92), however, the SOC-subscales (comprehensibility, manageability, meaningfulness) were correlated with each other. A principal component factor analysis did not identify the 3-factor structure of the SOC-Scale. It appears that the best solution consists of one global factor. The newly developed SOC-L9, conceptualized as an unidimensional scale, is a reliable and valid instrument, which allows to assess the SOC economically. In our study the Sense of Coherence depended on age and gender. Women and older people reported a lower SOC. Furthermore we found significant associations between SOC and different subjective health measures. A high SOC was associated with both a lower extent of subjective body complaints and somatoform symptoms and with minor health-related problems in daily living. PMID- 11199112 TI - [Promotional Prize of the German Lung Foundation, "Production of nitric oxide in human respiratory tract"]. PMID- 11199113 TI - [Recruitment of immunocompetent cells in a transplanted lung is not impaired despite incompletel reinnervation]. AB - BACKGROUND: It is not clear whether surgical intervention during lung transplantation which includes cutting vegetative nerves, lymphatic vessels and bronchial arteries, leads to alterations in immune responses. Thus, it was studied in an animal model whether an induced pulmonary immune reaction after syngenic lung transplantation was impaired without the influence of immunosuppression and rejection. The recruitment of leukocytes and the status of reinnervation was examined. METHODS: Syngenic transplantation of the left lung was performed in Lewis rats without rejection and therefore without immunosuppressive therapy. In a subgroup of animals host and donor leukocytes were distinguished. An ovalbumin (OVA)-specific pulmonary immune response was induced four months after transplantation. Bronchoalveolar lavage (BAL) and interstitial leukocytes were examined using flow cytometry and immunocytology, comparing the right lung and the grafted left lung. Immunohistology was performed to detect nerve fibers on cryostat sections. RESULTS: An induced cellular inflammation was observed in the right host lung as well as in the grafted left lung. However, the CD4 T cell numbers in the BAL were increased in the left lung. Single donor-type leukocytes could still be observed four months after transplantation. A partial reinnervation was found. CONCLUSIONS: The recruitment of immune cells into the lung interstitium and bronchoalveolar space of grafted lungs is not impaired. The incomplete reinnervation has no influence on leukocyte recruitment. PMID- 11199114 TI - [Correlation of plasma glutathione and total IgE level: evidence for a regulatory role of antipxodants in vivo]. AB - BACKGROUND: Atopy is characterized by increased levels of circulating immunoglobulin E (IgE). Moreover, elevated IgE levels are frequently observed in HIV-infected individuals and are of prognostic significance in these patients. Several In vitro studies have established an association of intracellular antioxidants like glutathione with IgE production by B-lymphocytes, suggesting a regulatory role of these substances in IgE synthesis. However, in vivo data consistent with these findings have not been reported. METHODS: Total IgE levels, CD4(+)-lymphocyte count and plasma glutathione were determined in non-atopic, HIV positive individuals. RESULTS: 27 HIV-positive subjects (mean age Alter +/- SD: 43 +/- 11 years, 85% males) were studied. Mean CD4(+)-lymphocyte count was 250 +/ 136/microliter. The median serum IgE level was 85.3 U/ml (Range: 3-1298 U/ml), and the mean plasma glutathione concentration was 2.08 +/- 0.7 muMol. Plasma glutathione was significantly correlated with CD4(+)-lymphocyte count (r = 0.37; p = 0.05), and was inversely related to total IgE (r = -0.46; p = 0.01). CONCLUSIONS: Plasma glutathione and total IgE levels are negatively correlated in HIV-positive individuals. This observation supports the concept of a regulatory role of antioxidants and IgE synthesis in vivo. Further studies aiming at the possible significance of these mechanisms in atopic patients are clearly warranted. PMID- 11199115 TI - [Value of retrospective assessment of the Epworth Sleepiness Scale after long term CPAP therapy in obstructive sleep apnea disorder]]. AB - BACKGROUND: Daytime-sleepiness is the main symptom of the obstructive sleep apnoea syndrome. Standarized questionnaires (e.g. the Epworth sleepiness scale = ESS) have become useful diagnostic tools. In this study we investigated wether there is a difference between the estimation of initial "pre-treatment" daytime sleepiness (by ESS) compared to the retrospective ESS score after implementation of CPAP therapy. PATIENTS AND METHODS: We included 46 patients (RDI 39/h +/- 20.2, CPAP pressure 8 cm/H2O +/- 1.7, daily use of 5.8 h +/- 1.8, RDI with CPAP 7.6/h +/- 5.3). We examined the ESS score before CPAP-therapy (ESS-base) in comparison to the retrospective estimation of the initial conditions after one year of CPAP-therapy (ESS-retro). RESULTS: There was no statistical significant difference between ESS base (11.7 +/- 4.6) and ESS-retro (12.7 +/- 5.2). ESS decreased to 5.4 +/- 3.7 by CPAP-therapy (p < 0.01). CONCLUSION: From a chronological point of view ESS is a consistent parameter of daytime sleepiness. Hence, the retrospective estimation of pre-CPAP ESS can be considered as a useful diagnostic tool. PMID- 11199116 TI - [Prevalence of stroke and transitory ischemic attacks in obstructive sleep apnea: a retrospective analyis so f 187 consecutive patients]. AB - BACKGROUND: Obstructive sleep apnea (OSA) is presumed to be significantly associated with cerebrovascular disease; however, there are no consistent epidemiological data providing proof of such a link. Hence, the aim of the present study was to determine the prevalence of stroke and transient ischemic attack (TIA) in patients with OSA. PATIENTS AND METHODS: 187 consecutive patients with a polysomnographically verified diagnosis of OSA who had been admitted to our sleep laboratory during 1/98-3/00 were retrospectively analysed. RESULTS: The prevalence of stroke and TIA was 7%. This rate was lower if compared with those for coronary artery disease and arterial hypertension in the same study cohort (14% and 53% respectively). The 13 OSA patients with stroke were elderly overweight men (age: 64 +/- 1.7 years, BMI: 31.4 +/- 1.1 kg/m2). They had quite severe OSA (AHI: 43 +/- 5/h) and almost all of them suffered from arterial hypertension. In all cases, the insult was caused by cerebral or brain stem ischemia. None of the patients presented with persistent neurological deficits. The mean latency period between the occurrence of stroke or TIA and the diagnosis of OSA was 41.9 +/- 11.3 months. CONCLUSION: In summary, the prevalence of stroke or TIA in our series of 187 consecutive OSA patients was 7%. Further prospective studies controlling for confounding factors such as age, body weight and arterial hypertension are needed to clarify the risk potential of OSA for the development of cerebrovascular disorders. PMID- 11199117 TI - [Studies with the fully automated EEG sleep analysis system QUISI]. AB - To judge sleep reliably would be interesting not only for outpatient sleep diagnostics, but also in the inpatient sphere. A step in this direction is the easy-to-apply fully automated sleep-EEG-analysis system QUISI. Nine males patients with obstructive sleep apnoea syndrome were examined simultaneously by polysomnography and the QUISI system. A comparison of the sleep profiles evaluated by polysomnographic recordings using Rechtschaffen and Kales' rules with the automated classification using QUISI recording shows that the difference of the sleep parameters sleep period time (SPT), total sleep time (TST), REM, stage 1, stage 2, slow-wave sleep and the awake stage of maximum five patients ranged between +/- 10 minutes, respectively +/- 5 per cent. Only two of nine sleep profiles could be compared as far as the sequence of the sleep stages was concerned. According to our results it is important to edit the original data and to treat the fully automated sleep profile. We cannot recommend QUISI to establish sleep profiles for the obstructive sleep apnoea syndrome. PMID- 11199118 TI - [Efficient ventilator weaning]. PMID- 11199119 TI - [Diagnosis of acute pulmonary embolism. Recommendations of the German Society of Pneumology]. PMID- 11199120 TI - [Fractional CO uptake in breathing at risk for detection of diffusion disorder. Comparative cross-sectional and longitudinal validation with the single breath method]. AB - Methodically it is very simple to determine fractional CO-uptake (FCO) from inspiratory and mean expiratory CO-concentrations. In two longitudinal studies the single-breath-TCO (49 patients) and FCO (813 patients) have been compared. The oscillations of DCO are smaller than those of TCO, but it remains unclear which method for determination of CO-transfer has a higher validity. PMID- 11199121 TI - [Recommendations for updated lung function reference values from the SAPALDIA study]. PMID- 11199122 TI - Antioxidant and antimicrobial activity of Foeniculum vulgare and Crithmum maritimum essential oils. AB - The essential oils obtained from Crithmum maritimum L. (marine fennel) and two samples of Foeniculum vulgare Miller (common fennel) were analysed by GC and GC MS and assayed for their antioxidant and antibacterial activities. The antioxidant activity of the oils was evaluated by two lipid model systems: a modified thiobarbituric acid reactive species (TBARS) assay and a spectrophotometric detection of hydroperoxydienes from linoleic acid in a micellar system. The oils demonstrated antioxidant capacities, comparable in some cases to that of alpha-tocopherol and butylated hydroxytoluene (BHT), used as reference antioxidants. Concerning the antimicrobial tests the essential oils were assayed against twenty-five genera of bacteria, including animal and plant pathogens, food poisoning and spoilage bacteria. Oils from the two samples of F. vulgare showed a higher and broader degree of inhibition than that of C. maritimum. PMID- 11199123 TI - Anti-hepatitis B virus effects of wogonin isolated from Scutellaria baicalensis. AB - By using an HBV-producing cell line (MS-G2) in vitro culture system, we found that wogonin isolated from Scutellaria baicalensis can suppress HBV surface antigen production (P < 0.001) without evidence of cytotoxicity. By assaying the endogenous HBV DNA polymerase activity, we found that both the relaxed circular and the linear forms of HBV DNA are significantly reduced in the wogonin-treated group. Wogonin deserves to be further evaluated for the treatment of human HBV infection. PMID- 11199124 TI - Mitogenic effect of Parkia speciosa seed lectin on human lymphocytes. AB - Mitogenic activity of a lectin, purified from Parkia speciosa seeds, on the isolated peripheral blood lymphocytes taken from normal blood donors and patients with esophageal carcinoma was examined using [3H]thymidine incorporation. The lectin increases the incorporation of [3H]thymidine into DNA of human lymphocytes. The activity of the lectin increased as its concentration was increased and then declined once the concentration passed an optimum point. The stimulant effect was also expressed using a proliferation index (PI): the ratio of [3H]thymidine incorporated into lymphocytes in the presence and absence of the lectin. The mitogenic activity of the lectin is comparable to those of the known T-cell mitogens, such as concanavalin A, phytohaemagglutinin, and pokeweed mitogen. Only slightly less responsiveness was observed in the case of lymphocytes from esophageal cancer compared to lymphocytes from normal donors. PMID- 11199125 TI - Effect of ginseng total saponin on extracellular dopamine release elicited by local infusion of nicotine into the striatum of freely moving rats. AB - We investigated the effect of ginseng total saponin (GTS) on nicotine-induced dopamine (DA) release in the striatum of freely moving rats using an in vivo microdialysis technique. In order to further characterize the mechanism by which GTS affects DA release, the effect of GTS on K(+)-induced DA release was also examined. Local infusion of nicotine (1, 5, and 10 mM) into the striatum produced a dose-dependent increase in extracellular DA in dialysate samples (maximal response = 154.0 +/- 10.8%, 308.1 +/- 55.7%, and 499.9 +/- 77.9% over basal levels, respectively). GTS (100 mg/kg i.p.) had no effect on basal levels of extracellular DA. However, GTS inhibited maximal DA release induced by intrastriatal infusion of nicotine (1, 5, and 10 mM) by 35.3%, 36.6%, and 58.5%, respectively. Intra-striatal infusion of high K+ solution (100 mM) produced an increase in extracellular DA in the striatum (maximal response = 796.6 +/- 98.8% over basal levels). However, GTS had no effect on the K(+)-induced increase in extracellular DA. The present study demonstrated that GTS inhibited striatal DA release stimulated by local infusion of nicotine. This may reflect the blocking effect of GTS on the striatum-related behavior induced by nicotine as well as other psychostimulants. The results also suggest that GTS may act on presynaptic nicotinic acetylcholine receptors or receptor-operated Na+ channels in dopaminergic nerve terminals, but not on voltage-sensitive ion channels. PMID- 11199126 TI - Hepatocurative effect of picroliv and silymarin against aflatoxin B1 induced hepatotoxicity in rats. AB - Single doses of aflatoxin B1 (2 mg/kg, i.p.) caused significant increases in the activities of tau-glutamyl transpeptidase, 5'-nucleotidase, acid phosphatase and acid ribonuclease, and decreases in the activities of succinate dehydrogenase and glucose-6-phosphatase in liver, after 8 weeks. The level of lipid peroxides, DNA, RNA, and cholesterol increased while glycogen decreased. It also increased the serum level of transaminases, sorbitol dehydrogenase, glutamate dehydrogenase, lactate dehydrogenase, acid phosphatase, alkaline phosphatase, and bilirubin. Oral administration of picroliv (25 mg/kg/day for 15 days), a standardised iridoid glycoside fraction of Picrorhiza kurroa, 6 weeks after aflatoxin B1 toxication, significantly prevented the biochemical changes induced in liver and serum of aflatoxin B1 treated rats. The hepatocurative effect of picroliv and silymarin, a plant based standard hepatoprotective are comparable. PMID- 11199127 TI - Panax vietnamensis protects mice against carbon tetrachloride-induced hepatotoxicity without any modification of CYP2E1 gene expression. AB - In order to explore the effect of Panax vietnamensis on carbon tetrachloride induced hepatotoxicity, mice were pretreated for 7 days with either crude extract or total saponins. Crude extract and total saponins dramatically decreased carbon tetrachloride-induced increase of serum GST alpha level (-50.0%, -49.5% respectively). Serum AST level was significantly decreased only with total saponins (-52.2%) and ALT level was slightly modified. In vitro experiments shown that both preparations at high concentrations (> 2000 micrograms/ml) are able to inhibit CYP2E1 enzymatic activity in mouse and human microsomes. However, we did not observe any modification of Cyp2e1 gene expression (enzymatic activity, protein and mRNA levels) in mice treated with either crude extract or total saponins. Taken together, these data demonstrated that Panax vietnamensis could be used as an hepatoprotectant. However, the mechanism of action is not associated with CYP2E1 expression, as previously suggested in vitro in rat for total saponins from Panax ginseng. PMID- 11199128 TI - Bioactive constituents of Conyza albida. AB - The bioactivity-guided fractionation of an active chloroform extract of Conyza albida led to the isolation of three alkenynes, deca-4,6-diyn-2-(Z)-enoic methyl ester (1), deca-4,6-diyn-2-(Z)-enoic ethyl ester (2) and deca-2,4-diene-4-hydroxy 6-yn-1,4-olide (3), and the terpenoid spathulenol (4), as the active toxic metabolites in the Artemia sp. lethality test. When tested in the KB cell cytotoxicity assay, compounds 1-4 demonstrated IC50 values of 52.2, 38.4, 117.9, and 83.8 microM, respectively. All compounds studied were inactive in the DNA methyl green and DNA strand scission assays, while compounds 3 and 4 showed moderate activity as inhibitors of human topoisomerase I. Compound 2 is reported here for the first time. PMID- 11199129 TI - Peroxidase activity in Aloe barbadensis commercial gel: probable role in skin protection. AB - A basic peroxidase (EC 1.11.1.7) (pl around 9.0) has been identified in commercial gel of Aloe barbadensis. In vivo, the activity is localised in the vascular system of inner aqueous leaf parenchyma. Some relevant properties of this basic peroxidase of Aloe have been investigated in leaf extract and in commercial gel where it is notably stable. The acid optimum pH (5.0) for activity and the low KM for H2O2 (0.14 mM) suggest that, when topically applied, Aloe peroxidase may scavenge H2O2 in skin surface. PMID- 11199130 TI - Bioactive coumarin derivatives from the fern Cyclosorus interruptus. AB - Three new coumarin derivatives, compounds 1-3, three new furanocoumarins, compounds 4-6, and a novel dioxocane derivative, compound 7, were isolated from the fern Cyclosorus interruptus (Willd.) H. Ito. Based on spectrometric and spectroscopic analysis (FAB or El mass spectrometry as well as 1D and 2D NMR experiments) their structures were characterised as 5,7-dihydroxy-6-methyl-4 phenyl-8-(3-phenylpropionyl)-1-benzopyran-2-one (1), 5,7-dihydroxy-6-methyl-4 phenyl-8-(3-phenyl-trans-acryloyl)-1- benzopyran-2-one (2), 5,7-dihydroxy-8-(2 hydroxy-3-phenylpropionyl)-6-methyl-4-phenyl-1- benzopyran-2-one (3), 8-benzyl 5,8-dihydroxy-6-methyl-4-phenylfuro[2,3-h]-1-benzopyran-2,9- dione (4), 8-benzyl 5,8 beta,9 beta-trihydroxy-6-methyl-4-phenyl-8,9-dihydro- furo[2,3-h]-1 benzopyran-2-one (5), 8-benzyl-5,8 beta,9 alpha-trihydroxy-6-methyl-4-phenyl-8,9 dihydro- furo[2,3-h]-1-benzopyran-2-one (6) and 5,11-dihydroxy-6-methyl-4-phenyl 11-(1-phenylmethyl)-7,10-dioxocane [5,6-h]-1-benzopyran-2,12-dione (7). For these compounds we propose the trivial names interruptins A-F. Compounds 1, 5/6 and 7 showed antibacterial activity while compounds 1 and 2 were cytotoxic to a KB cell line. PMID- 11199131 TI - Phytotoxic compounds from Xanthocephalum gymnospermoides var. eradiatum. AB - Investigation of the aerial parts of Xanthocephalum gymnospermoides var eradiatum led to the isolation of two new labdane-type of diterpenes, namely, 8 alpha,13S epoxylabdane-14S,15-diol (1) and methyl grindelate (2). In addition, grindelic acid (3), 7 alpha, 8 alpha-epoxygrindelic acid (4), 7 alpha-hydroxy 8(17)dehydrogrindelic acid (5), 17-hydroxygrindelic acid (6) and 4,5-epoxy-beta caryophyllene (7) were obtained. The isolated compounds were characterized by spectral means. The absolute configuration of compound 1 was established by chemical correlation with 8 alpha,13S-epoxy-15-nor-labdan-14-oic acid methyl ester of known absolute stereochemistry and by using the advanced Mosher's ester methodology. The results of the present investigation indicated that the known compound barbatol (8) could be an enantiomer of compound 1. Compounds 1-3 and 7 caused significant inhibition of the radicle growth of seedlings of Amaranthus hypochondriacus. PMID- 11199132 TI - Phytochemical investigation of Aglaia andamanica. AB - Four new compounds, the limonoid 24-epi-melianodiol (8), the tirucallane aglaiodiol (9), and the two cyclopentatetrahydrobenzopyran derivatives pyramidaglain A (11) and B (12) were isolated from the leaves of Aglaia andamanica Hiern (Meliaceae), together with the eleven known constituents beta sitosterol, beta-sitosterol glucoside, cycloart-23E-ene-3 beta,25-diol (1), three flavonoids 5-hydroxy-3,4',7-trimethoxyflavone (2), retusin (3) and pachypodol (4), the tirucallane 24-epi-piscidinol A (5), the lignan yangambin (6), the limonoid melianodiol (7), the bisamide pyramidatine (10) and the amino acid N methyl-trans-4-hydroxy-L-proline (13). All structures were established by means of detailed spectroscopic analysis. PMID- 11199133 TI - Radical scavenger activity of phenylethanoid glycosides in FMLP stimulated human polymorphonuclear leukocytes: structure-activity relationships. AB - Radical scavenger activities of 21 phenylethanoid glycosides, including 15 ester derivatives of caffeic, ferulic, vanillic and syringic acid as well as 6 deacyl derivatives were determined by quantifying their effects on the production of reactive oxygen species (ROS) in a luminol-enhanced chemiluminescence assay with formyl-methionyl-leucyl-phenylalanine (FMLP) stimulated human polymorphonuclear neutrophils (PMNs). All phenylethanoids acylated with phenolic acids showed strong antioxidant activity whereas the deacyl derivatives were more than 30-fold less active. Therefore, the antioxidant activity is mainly related to the number of aromatic methoxy and hydroxy groups and the structure of the acyl moiety (C6 C1 or C6-C3). In contrast, modification of the sugar chain or replacement of hydroxy groups by methoxy groups in the acyl or the phenylethanoid moiety is of minor importance. The position of the acyl moiety is without significance. Free caffeic, ferulic, vanillic and syringic acid are less active compared to the phenylethanoid derivatives. This points to the importance of dissociation and lipophilicity of these acids in a cellular test system. PMID- 11199134 TI - Tetrahydrofuran lignans from Illicium floridanum and their activity in a luminol enhanced chemiluminescence assay. AB - Two lignans of the tetrahydrofuran type, di-O-methyltetrahydrofuroguaiacin B (1) and (+)-veraguensin (2) were isolated from fruits and leaves of Illicium floridanum Ellis (Illiciaceae). These compounds are the first genuine lignans isolated from the genus Illicium. We investigated their radical scavenging potency towards 1,1-diphenyl-2-picrylhydrazyl radical reagent and their influence on luminol enhanced chemiluminescence (CHL) induced by different stimuli in human polymorphonuclear neutrophils (PMN). Both compounds were inactive in the TLC assay for chemical radical scavenge. In the PMN assay, the symmetric lignan 1 at concentrations below 1.0 microM displayed a strong inhibition of CHL induced by N formyl-methionyl-leucyl-phenylalanine (fMLP). At concentrations above 5 microM, 1 led to a pronounced increase of fMLP induced CHL. When CHL was stimulated with opsonized zymosan, both compounds were completely inactive. Thus, 1 must interfere selectively with a step in the signal cascade evoked by fMLP. In addition to their known PAF-receptor antagonism tetrahydrofuran lignans may thus also interfere with inflammatory responses by inhibition of free radical formation. PMID- 11199135 TI - Inhibition of neutrophil elastase activity by cinnamic acid derivatives from Cimicifuga racemosa. AB - Caffeic acid, fukinolic acid as well as cimicifugic acids A, B, E and F isolated from the rhizomes of Cimicifuga racemosa (Ranunculaceae) inhibited the activity of neutrophil elastase (EC 3.4.21.37) in a dose-dependent manner. An IC50 of 93 mumol/L was determined for caffeic acid and 0.23 mumol/L for fukinolic acid. Cimicifugic acid A inhibited the enzyme with an IC50 of 2.2 mumol/L, cimicifugic acid B with 11.4 mumol/L, and cimicifugic acid F with 18 mumol/L. Cimicifugic acid E was only a very weak inhibitor. PMID- 11199136 TI - Galloyl esters from rhubarb are potent inhibitors of squalene epoxidase, a key enzyme in cholesterol biosynthesis. AB - Galloyl glucoses and galloyl proanthocyanidins obtained from rhubarb (Rhei Rhizoma, Rheum palmatum L., Polygonaceae); e.g. 1,2,6-tri-O-galloyl-beta-D glucose (IC50 = 0.63 microM), 1,6-di-O-galloyl-2-O-cinnamoyl-beta-D-glucose (IC50 = 0.58 microM), procyanidin B-2 3,3'-di-O-gallate (IC50 = 0.54 microM), and procyanidin B-5 3,3'-di-O-gallate (IC50 = 0.55 microM), were found to be potent inhibitors of rat squalene epoxidase (SE). The inhibition at submicromolar level was far more potent than that of chemically synthesized substrate analogs. It was demonstrated for the first time that the cholesterol-lowering effect of rhubarb may be attributed to the potent inhibition activities of SE, a rate-limiting enzyme of cholesterol biogenesis. PMID- 11199137 TI - Antimycobacterial and antiplasmodial cyclodepsipeptides from the insect pathogenic fungus Paecilomyces tenuipes BCC 1614. AB - Bioassay-guided fractionation of the crude extract from the insect pathogenic fungus Paecilomyces tenuipes BCC 1614 led to the isolation and identification of two antimycobacterial and antiplasmodial cyclodepsipeptides, beauvericin and beauvericin A. PMID- 11199138 TI - In vitro cytotoxicity of norviburtinal and isopinnatal from Kigelia pinnata against cancer cell lines. AB - Crude dichloromethane extracts of Kigelia pinnata stem bark and fruit showed cytotoxic activity in vitro against cultured melanoma and other cancer cell lines using the Sulphorhodamine B assay, which was used for bioassay-guided fractionation. Thin layer chromatography (TLC) examination of the most active fractions of both stem bark and fruits showed the presence of the same major components which were found to be norviburtinal and beta-sitosterol. Norviburtinal was found to be the most active compound but had little selectivity for melanoma cell lines whilst isopinnatal also showed some cytotoxic activity. beta-Sitosterol was found to be comparatively inactive. HPLC analysis of the crude extract showed that the amount of norviburtinal present in the plant material did not account for all of the activity of the total extracts. PMID- 11199139 TI - Protective effects of green tea catechins against asbestos-induced cell injury. AB - Green tea extract was found to provide a strong protective effect against asbestos-induced injury of peritoneal macrophages and red blood cells in vitro. The main polyphenolic constituents of green tea extract, (-)-epicatechin gallate (ECG) and (-)-epigallocatechin gallate (EGCG), were also efficient in preventing injury of cells following exposure to asbestos fibers. The protective efficacies of EGCG and ECG expressed as IC50 values were, respectively, 10 microM and 12 microM if peritoneal macrophages were injured by chrysotile and 4 microM and 5 microM in the case of crocidolite-induced cell injury. Antiradical and chelating properties of ECG and EGCG were evaluated and it was concluded that the protective effect of catechins against asbestos-induced injury may be related to both scavenger properties towards to superoxide anion and the ability to chelate iron ions. PMID- 11199140 TI - Smooth muscle relaxing activity of gentiopicroside isolated from Gentiana spathacea. AB - Bioassay directed fractionation of the (1:1) chloroform-methanol extract of Gentiana spathacea H.B.K (Gentianaceae) led to the isolation of gentiopicroside (gentiopricrin) (1), the major spasmolytic component of the plant. Gentiopicroside inhibited, in a concentration-dependent manner, the spontaneous contractions of isolated guinea pig ileum. Contractions induced by histamine, acetylcholine, BaCl2 and KCl on the ileum were also significantly blocked by this monoterpene glucoside, which suggests that this compound might be interfering with calcium influx into the smooth muscle cells. PMID- 11199141 TI - Antimicrobial triterpenoids from Licania heteromorpha. AB - Six triterpenoids having a lupane and oleane skeleton were isolated from the leaves and young branches of Licania heteromorpha Bentham var. heteromorpha and were identified as: betulinic acid 1, alphitolic acid 2, 3 beta-O-trans-p coumaroyl alphitolic acid 3, 3 beta-O-cis-p-coumaroyl alphitolic acid 4, 3 beta-O trans-p-coumaroyl maslinic acid 5, 3 beta-O-cis-p-coumaroyl maslinic acid 6. The antimicrobial activity of these compounds was evaluated in vitro on clinically isolated microorganisms employing a microdilution method. Compounds 2, 3, 5, and 6 showed antimicrobial activity on Gram-positive bacteria and yeasts, whereas none of the six triterpenoids were active against Gram-negative organisms. PMID- 11199142 TI - Antinociceptive profile of hodgkinsine. AB - To further understand the mechanism of analgesic activity and structural requirements of pyrrolidinoindoline alkaloids identified in Psychotria colorata, we here report the analgesic activity of the trimer hodgkinsine on thermal and chemical models of analgesia. Results show that hodgkinsine produces a dose dependent naloxone reversible analgesic effect in thermal models of nociception, suggesting that activation of opioid receptors participates in hodgkinsine's mode of action. Hodgkinsine shows a potent dose-dependent analgesic activity against capsaicin-induced pain, indicating the participation of NMDA receptors in hodgkinsine-induced analgesia. Such a dual mechanism of action may be of interest for developing innovative analgesics. PMID- 11199143 TI - Isolation of taxoids from cell suspension cultures of Taxus wallichiana. AB - Cell suspension cultures of stem-derived callus of Taxus wallichiana in MS-F culture media were found to produce three C-14 oxygenated taxoids and one regular taxoid. The taxoids were identified as yunnanxane (1), 2 alpha, 5 alpha, 10 beta, 14 beta-tetraacetoxy-4(20),11-taxadiene (2), 2 alpha, 5 alpha, 10 beta-triacetoxy 14 beta-(2-methyl)-butyryloxy-4(20),11-taxadiene (3) and 1 beta-hydroxybaccatin I (4). PMID- 11199144 TI - Chemical variations in the essential oil of Sideritis tragoriganum. AB - The essential oil composition from Sideritis tragoriganum has been investigated by capillary gas chromatography and gas chromatography-mass spectrometry. Among the 47 identified mono- and sesquiterpenes, alpha-bisabolol is the most prominent component. Correlation analysis of essential oil components from this population of S. tragoriganum with two other geographically distinct populations revealed the existence of unrelated chemical types. PMID- 11199145 TI - Quantitative changes of dianthrones, hyperforin and flavonoids content in the flower ontogenesis of Hypericum perforatum. AB - Samples of Hyperici herba were obtained by harvesting Hypericum perforatum L. in different plant development stages. The relation of flower development phases in the drug's flower fraction was examined. The HPLC method was then employed for the analysis of the content of secondary metabolites in different flower ontogenesis phases. The content of dianthrones, derivatives of quercetin and hyperforin increased from the first bud phases (0.29%, 0.80%, and 2.47%, respectively) to flowers just opened (1.04%, 4.23% and 6.60%, respectively). The content of dianthrones and quercetin glycosides then decreased (in unripe fruits 0.11% and 0.08%, respectively), whereas the amounts of hyperforin increased to 8.07% in fruits. The content of I3,II8-biapigenin increased from 0.21% in small buds to 1.04% in buds just before opening and has then decreased gradually to a value of 0.02% in fruits. Rutin was not detected in the samples. PMID- 11199146 TI - 3-Acetoxy group of genuine AKBA (acetyl-11-keto-beta-boswellic acid) is alpha configurated. AB - The pentacyclic triterpenoid 3-acetyl-11-keto-beta-boswellic acid (AKBA) from the resin of Boswellia spec. is a potent inhibitor of 5-lipoxygenase (5-LO). We noticed discrepancies in the nomenclature and stereochemistry of the 3-acetoxy group of boswellic acids. Isolation of AKBA under mild conditions and the data from the first X-ray crystallography study evidence the 3 alpha-orientation of AKBA's acetoxy function. PMID- 11199147 TI - Sesquiterpenes from the leaves of Ligularia fischeri var. spiciformis. AB - From the leaves of Ligularia fischeri var. spiciformis, a new eremophilanolide, 8 alpha-methoxy-6-oxoeremophil-7(11)-en-12,8-olide (6-oxoeremophilenolide) and a eudesmane-type sesquiterpene, (+)-intermedeol were isolated. The structures were determined on the basis of 2D-NMR spectral data. Data on cytotoxicity showed that the latter was clearly more potent than the former compound. PMID- 11199148 TI - [Lung maturation therapy with glucocorticoids in threatened premature labor. Considerations of risk-benefit in evidence-based medicine]. AB - Prematurity is a major cause of perinatal morbidity and mortality. Antenatal administration of glucocorticoids improves the neonatal outcome of preterm born infants. 1994 the NIH published recommendations for the use of glucocorticoids for women at risk of preterm delivery. A recent evaluation by the Cochrane Collaboration in 1999 showed that antenatal administration of glucocorticoids significantly reduced the rate of RDS and IVH in the gestational age between 24 and 34 weeks. Consequences of repeated courses of antenatal glucocorticoids are not sufficiently studied. The effectivity and safety regarding birth weights, infectious diseases, and the best timing remains unknown. Administration of glucocorticoids lowers fetal activity and heart rate variability. Effects on fetal growth, maternal and fetal immunosystem, and the development of atopic diseases are controversely discussed. Thus preterm labour not leading to a cervical ripening is not necessarily a reason for antenatal glucocorticoids. Antenatal glucocorticoids with PROM do not lower the rate of RDS but of IVH. No prospective randomized trial evaluated the effectivity of antenatal glucocorticoids in diabetes mellitus and IUGR. In preeclampsia beta-methason could improve the rate of RDS and the neonatal outcome. Still our knowledge of antenatal glucocorticoid administration is not sufficient. But despite possible (longtime-) risks for mother and child the administration of glucocorticoids according to the guidelines of the NIH is a major part in the treatment of prematurity and improves the outcome of premature infants. The indication for multiple courses of glucocorticoids should be considered carefully. PMID- 11199149 TI - [HIV/AIDS in gynecology. On the treatment readiness of established gynecologists for HIV positive women]. AB - BACKGROUND: Decreasing vertical transmission rates of HIV due to highly active antiretroviral therapy regimens faciliate the choice for childbearing in HIV positive women. Recent trends in epidemiology of HIV show increasing incidence of HIV-related gynecologic diseases. These facts implicate the question about the role of gynecologists in primary care of HIV-infected women and furthermore about the use of health services by HIV-infected women. MATERIALS AND METHODS: 143 of the total of 298 office-based gynecologists practicing in Vienna (41%) completed a questionnaire to assess their knowledge, attitudes, and practice with respect to HIV-infection and AIDS. In addition, personal interviews with 30 HIV-positive women were conducted. RESULTS: Although about 75% of the gynecologists are willing to care for HIV-positive women in their private practice, only about a third of them already care and 17.9% refuse to care for these patients. More than two thirds of the gynecologists refuse to care for intravenous drug users and patients with manifestations of AIDS. Barriers to care are the fear to be confronted with the psychosocial problems of patients, the fear to need more time to care for these patients and the fear of a lack in knowledge about HIV/AIDS. HIV-positive women are highly satisfied with care, although the majority of the women reported about a lack of confidentiality and therefore did not inform their gynecologist about their HIV-infection. CONCLUSIONS: The physician-patient relationship of gynecologists and HIV-positive women is characterized by gynecologist's barriers to care on the one hand, on the other hand HIV-positive women report about a lack of confidentiality, which often is associated with a delay in seeking medical care. DISCUSSION: A strategy to overcome gynecologist's barriers in care for HIV-positive women is medical education. The improvement of the physician-patient relationship will enhance the effects of HIV/STD risk assessment as well as the quality of care. PMID- 11199150 TI - [Intrauterine growth retardation--perinatal mortality and postnatal morbidity in a perinatal center]. AB - OBJECTIVES: The intrauterine growth retardation (IUGR) contributes specially to perinatal mortality and morbidity. An effective treatment is not yet available. The purpose of this study is to analyse the perinatal data of a cohort with IUGR infants including mortality and morbidity and to describe prematurity and IUGR as a combination of high risk. STUDY DESIGN: We have analysed the perinatal data of a cohort of 220 patients with IUGR-infants including mortality and morbidity. Regularly we examined fetal ultrasonographic growth, doppler measurements of fetal and maternal vessels and CTG, as well as indicated amniocentesis, placentesis and cordocentesis. Entry criteria were: normal menstrual period before pregnancy, clear gestational age, complete history of pregnancy. RESULTS: At the Department of Gynaecology & Obstetrics, University Hospital, Homburg/Saar, the incidence of IUGR (< 10th Percentile) in premature babies and newborns was 13.1% over five years (1993-1997). The percentage of premature babies with IUGR was 18.6%. The overall mortality was 4.1%, the perinatal mortality was 3.6% and the neonatal mortality was 2.7%. In 1.4% intrauterine foetal death was observed, all associated with a birthweight below the 3th percentile. The average duration of pregnancy was 34 + 4 weeks. A high perinatal mortality of 13.1% and an overall mortality of 14.7% was observed. 11.4% of the premature babies with IUGR showed deformities and about 2% presented chromosome aberrations. 46.4% of children have been transferred to the Neonatal Intensive Care Unit. 57.1% of the postnatal complications have been related to the lungs, 26.5% to the cardiovascular system and 14.3% to the cerebrum. Maternal complications were referred to: SIH/EPH gestosis (65.4%), HELLP-syndrome (5.8%), nicotine abuse (31.4%), pregnancy anaemia (17.3%) and gestational diabetes with insuline therapy (7.7%). On the placental site the most noticeable conditions have been placental insufficiency (40.6%) and placental infarction (28.7%). CONCLUSION: Children with IUGR are exposed to high perinatal mortality and postnatal morbidity. Premature babies in association with an IUGR are at high risk. The surveillance of the pregnant women and the new-born children should be performed in a perinatal centre. PMID- 11199151 TI - [Damage to the brachial plexus in vaginal delivery from breech presentation- correlation with reducing the extended arm]. AB - BACKGROUND: Brachial plexus injuries in foetuses delivered spontaneously by breech presentation is very rare. The aim of this study was to evaluate the frequency of brachial plexus injuries in connection with the rate of the reduction of the extended arm. MATERIALS AND METHODS: In our retrospective study we examined 1194 vaginally intended breech deliveries (> 32 completed weeks) for the frequency of extended arms and subsequent plexus brachialis palsies. RESULTS: One brachial plexus injury occurred in 796 vaginally delivered newborns (1.2@1000). The outcome corresponds with the frequency of brachial plexus palsy in spontaneous deliveries with cephalic presentation (1@1000). The mean frequency of reduction of the extended arm in vaginal deliveries in breech is 10-20%. CONCLUSION: We found that the rate of reduction of the extended arm was not associated with an increase in morbidity of newborns. DISCUSSION: Many reports in the literature demonstrate that a higher rate of caesarean section does not prevent these severe foetal injuries. Noxious factors already occurring during the prenatal phase of development can be suspected as possible causes. PMID- 11199152 TI - The concentration of alpha 1-antitrypsin in the maternal serum after delivery of normal and small for gestational age infants. AB - BACKGROUND: alpha 1-antitrypsin (A-1-AT) is an acute-phase protein. It is present in plasma and other extracellular fluids and in human trophoblastic tissue. It accounts for 80 to 90 per cent of antiprotease reactions occurring in plasma. It has the ability to greatly affect enzyme activity and plays an important role in immunomodulatory processes. MATERIALS AND METHODS: The purpose of the study was to determine the plasma concentration of A-1-AT in mothers giving birth to hypotrophic (small for gestational age, SGA), and eutrophic (appropriate for gestational age, AGA) infants. 33 women who gave birth to SGA infants and 36 women who gave birth to AGA infants participated in the study. The control group consisted of 30 non-pregnant women who were of reproductive age. All women gave birth at term. To measure A-1-AT concentration, we used the diffusion method described by Mancini et al. RESULTS: The highest concentration of A-1-AT (379 mg/dl) was found in women giving birth to SGA infants, compared with 345 mg/dl for women giving birth to AGA infants. In the control group, the concentration was found to be 270 mg/dl. CONCLUSIONS: Statistical analysis of the results showed a significant difference between the two groups of women gave birth and between each parturient compared with control subjects. Increasing concentration of A-1-AT in the plasma of women in labor may be the result of an acute phase reaction triggered by the stress during parturition. Additionally, increased concentrations of A-1-AT in women who gave birth to SGA rather than AGA infants suggest that it may play a role in the processes of intrauterine growth retardation (IUGR). PMID- 11199153 TI - [Primary hyperparathyroidism in pregnancy--a case report]. AB - BACKGROUND: Primary hyperparathyroidism during pregnancy is rare. The incidence of primary hyperparathyroidism in women of child-bearing age is estimated to be approximately 8 cases per 100,000 population per year. CASE REPORT: We provide a case report of a 33-year old pregnant woman, in whom primary hyperparathyroidism was diagnosed because of neonatal hypocalcemia two days after delivery. There was a history of recurrent urinary tract infections with hydronephrosis on the left side. The woman had been treated on an outpatient basis by an urologist, nephrostomy had been performed. After delivery, nephrolithiasis was diagnosed by x-ray and treated endoscopically. Parathyroid adenoma was found and removed successfully. DISCUSSION: Due to physiological changes of calcium metabolism primary hyperparathyroidism is often without symptoms during pregnancy. Operative elimination of adenoma as a frequent cause of primary hyperparathyroidism reduces maternal and fetal morbidity and mortality. CONCLUSIONS: In pregnant women with hydronephrosis on the left side primary hyperparathyroidism should be considered. If undetected, hyperparathyroidism causes considerable morbidity, not only for the mother but also for the child. PMID- 11199154 TI - [Ultrasound and endoscopic image of exencephaly (acrania) in the 12th week of pregnancy]. AB - BACKGROUND: Acrania is a rare congenital anomaly of unknown pathogenesis, in which the flat bones of the cranial vault are absent and the facial bones are normally present. MATERIALS AND METHODS: We present a case of a 4th gravida, who had already born 2 children with acrania and came for an ultrasound examination in the 12th week of gestation. RESULTS: By transvaginal ultrasonography it was possible to diagnose fetal acrania already in the 12th week. By hysteroscopy at the same time we could see, that the brain was covered by a thin membrane, the facial bone and the shape of the cranium were normal. CONCLUSIONS: By hysteroscopy it was possible to confirm the diagnosis and to detect additional malformations. This fetus showed a small omphalocele, hexadactylism on both sides and clubfeet on both sides. DISCUSSION: By hysteroscopy in this early week of pregnancy we could demonstrate, that acrania is an independent anomaly and not the first stage of an anencephaly as reported by other authors. Hysteroscopy also offers the advantage of viewing the intact fetus before pregnancy termination. PMID- 11199155 TI - Evaluating mutant mice: anatomic pathology. AB - As the human and mouse genome projects approach their goals, initiatives in functional genomics are advancing. When the nucleotide sequences are available, identification of gene functions will assume even greater importance. Determination of gene products and their proximal biochemical functions provide a part of the picture, but determination of their functions in the context of the whole organism is the ultimate goal. The manipulated mouse genome has become accepted as a model for understanding the genetic basis of human conditions and diseases. Consequently, biomedical research institutions have seen significant increases in the use of mice since the early 1980s, and these increases are largely attributable to the use of genetically modified mice. The role of comparative pathology in research on mutant mouse models of disease is increasing in response to these trends. Evaluation and phenotypic characterization of mutant mice, via clinical and anatomic pathology techniques, will be an important component of functional genomics initiatives. PMID- 11199156 TI - Hypotensive infarction of the spinal cord in a rhesus macaque (Macaca mulatta). AB - A 6.5-year-old male rhesus macaque (Macaca mulatta) was presented with acute paraplegia following a surgical procedure. During surgery, he experienced an acute hypotensive episode that required 3 hours of supportive therapy before hemodynamic stability was restored. Paraplegia remained unchanged until euthanasia 72 hours later. At necropsy, spinal cord segments T10-S3 had acute, massive panmedullary necrosis, which involved most of the central and middle spinal cord, sparing the peripheral white matter. Additional lesions included arterial border zone necrosis of the brain, centrilobular hepatic necrosis, and proximal renal tubular necrosis. The histologic findings of central spinal cord necrosis with a preserved rim of white matter is consistent with severely decreased flow in the anterior spinal artery. Such lesions can result from episodes of generalized hypoperfusion. Possible factors contributing to the hypotensive episode in this case included the addition of xylazine to ketamine and atropine in the preanesthetic medication, positioning during anesthesia, and decreased blood pressure during surgery. PMID- 11199157 TI - Cerebral vascular hamartomas in five dogs. AB - Vascular hamartomas are considered developmental lesions rather than true neoplasms. Reports of such anomalies in the canine brain are scarce, and their classification is confusing. This case series of vascular hamartomas from the brains of five dogs was characterized using histochemistry and immunohistochemistry, in addition to gross and microscopic findings. All five hamartomas were located in the telencephalon, three in the pyriform lobe, without any predilection for the left or right side. Each hamartoma consisted of a proliferation of thin-walled vessels which varied in caliber. These vessels were elastin-negative, with varying amounts of collagen and no muscular component. In four of the five hamartomas, lining cells were actin- and factor VIII-positive. All five hamartomas contained glial fibrillary acid protein (GFAP)-positive parenchyma at moderate to high frequency, and four contained neurofilament positive axons between component vessels. This report shows that vascular hamartomas in the canine brain are structural malformations for which immunohistochemistry is useful for accurate classification. PMID- 11199158 TI - The pagetoid variant of urothelial carcinoma in situ of urinary bladder in a cow. AB - A case of urothelial carcinoma in situ of urinary bladder is reported in a 10 year-old cow naturally grazing on bracken-infested land. The cow suffered from enzootic hematuria for more than 5 years. The presence of bovine papillomavirus type 2 (BPV-2) DNA sequences was detected by polymerase chain reaction. The carcinoma in situ was characterized by the presence of anaplastic cells with amphophilic cytoplasm and pleomorphic nuclei containing granular, irregularly dispersed chromatin. Focal areas within the tumor contained large isolated and/or clustered cells. These cells had pale acidophilic cytoplasm, large nuclei with single or multiple nucleoli, and well-defined borders resembling Paget's cells. Immunohistochemically, all malignant cells were negative for vimentin and S-100 and positive for cytokeratins. In addition, normal and neoplastic cells expressed fragile histidine triad (FHIT) protein; surprisingly, some pagetoid cells did not. FHIT, the tumor suppressor gene at 3p14.2, encodes a protein of 147 amino acids (16.8 kd) with diadenosine triphosphate hydrolase activity and is a common target of deletions in human cancers of epithelial origin. Antibody to laminin detected a continuous epithelial basement membrane, thus clearly showing that neoplastic changes were limited to urothelial cells without invading stromal tissue. To our knowledge, this is the first report of an unusual pattern of spread of urothelial carcinoma in situ in a cow. PMID- 11199159 TI - Expression of cyclooxygenase-2 in canine renal cell carcinoma. AB - Cyclooxygenase-2 (COX-2) has been shown to be the primary enzyme responsible for prostaglandin production during inflammation but is absent in most tissues under normal physiological states. High levels of COX-2 expression have been observed in the macula densa and thick ascending limbs of fetal kidneys; this expression declines to minimal levels during renal maturation. We hypothesized that the neoplastic cells of renal cell carcinoma (RCC) may revert to high expression of COX-2, and we evaluated its expression in three spontaneous cases of canine RCC by using immunohistochemical methods. The neoplastic cells of two of the three cases exhibited moderate to marked COX-2 immunoreactivity. These results suggest that some canine renal cell carcinomas express high levels of COX-2, which may play a role in the modulation of neoplastic cell growth. PMID- 11199160 TI - Necrotizing meningoencephalitis associated with cortical hippocampal hamartia in a Pekingese dog. AB - A 4-year-old male Pekingese dog was referred to the clinic with a history of recurrent seizures and progressive abnormal gait and behavior, which did not respond to treatment. At necropsy, a large cortical defect in the right temporo parietal cortex, malacia of subcortical white matter, right basal nuclei, and capsula interna, as well as abnormalities of the right hippocampus were observed. Histological examination of the brain revealed moderate to severe nonsuppurative meningoencephalitis in the left cerebral hemisphere and extensive infarction-like lesions with milder inflammation in the right hemisphere. In the right hippocampus, the pyramidal cells were arranged in a gyrus-like pattern and intermingled with gemistocytic and fibrillary astrocytes. The histopathological features of the inflammatory lesions were consistent with necrotizing meningoencephalitis and resembled those described in so-called Pug dog encephalitis. The hippocampal changes were interpreted as dysplasia (monolateral hippocampal cortical hamartia), unrelated to clinical signs and necrotizing inflammatory lesions. PMID- 11199161 TI - Special considerations in the evaluation of the hematology and hemostasis of mutant mice. AB - The study of mutant mice with altered or deficient hematopoietic or hemostatic gene products provides a challenge to the researcher, particularly when genetic alterations lead to lethal phenotypes. The following review provides a framework for understanding murine hematopoiesis, based on work with mutant mice, and details experimental approaches used to evaluate these animals. Mice with deficiencies in hemostatic and fibrinolytic system proteins are discussed, and the investigation of their phenotypes is reviewed. PMID- 11199162 TI - Activation of the immune system is the pivotal event in the production of wasting disease in pigs infected with porcine circovirus-2 (PCV-2). AB - Porcine circovirus (PCV)-2, a newly described single-stranded circular DNA virus pathogen of swine is the cause of postweaning multisystemic wasting syndrome (PMWS). In gnotobiotic piglets, PCV-2 infection alone produces asymptomatic infection without evidence of overt PMWS. Gnotobiotic piglets infected with PCV-2 were injected with keyhole limpet hemocyanin in incomplete Freund's adjuvant (KLH/ICFA), and the effects on virus production and development of PMWS were determined. In the first experiment, piglets were injected subcutaneously on the left hip and shoulder, and viral burden was assessed in regional lymph nodes draining the injection sites and in contralateral lymph nodes 13-14 days after infection. Immune activation increased the number of virus antigen-positive cells in draining lymph nodes and increased the amount of infectious virus recovered by 1-4 log10. In a second experiment, the effects of injections of KLH/ICFA with or without concurrent stimulation of peritoneal macrophages by intraperitoneal injections of thioglycollate broth on induction of PMWS was assessed. All immunized piglets developed moderate to severe PMWS, whereas none of the piglets infected with PCV-2 alone developed PMWS. In PMWS-affected piglets, extensive replication of PCV-2 was documented by both immunocytochemistry and quantitative viral titrations. Thus, immune activation is a key component of the pathogenesis of PCV-2-associated PMWS in swine. PMID- 11199163 TI - Ocular histopathology of Ehrlichial infections in the dog. AB - Histologic examination of eyes and brains of 27 dogs experimentally infected with either Ehrlichia canis, E. ewingii, E. chaffeensis, or human granulocytic ehrlichia (HGE) was conducted in the course of several experiments, the primary objectives of which were to investigate the susceptibility of the domestic dog to infection with various ehrlichial species and to assess the ability of ixodid tick species to acquire and transmit those infections. Uveitis and meningitis occurred in each of the dogs infected with E. canis but was not observed in dogs infected with the other Ehrlichia species. The inflammatory infiltrate was predominantly lymphocytic, monocytic, and plasmacytic; granulocytes were notably few. Ocular inflammation was most common and most intense in the ciliary body, becoming less intense in the choroid, iris, and retina, respectively. Meningitis was often accompanied by mild neuroparenchymal vascular cuffing and gliosis. The meningeal inflammatory cell infiltrate included a prominent monocyte population. Ocular and meningeal lesions were present in all E. canis-infected dogs from 22 through 200 days postexposure. Neither ocular nor brain lesions were observed with any of the other ehrlichial infections. PMID- 11199164 TI - Primary canine and feline nervous system tumors: intraoperative diagnosis using the smear technique. AB - The recent application of neuroimaging techniques in veterinary neurology has led to the accurate localization of many types of intracranial lesions but has also created a clinical need, particularly with brain tumors, for a specific intraoperative diagnosis. For human brain tumors, a smear technique has been used successfully for many years to provide an extremely rapid, highly accurate intraoperative diagnosis. In similar smear preparations of intracranial lesions, obtained either by computed tomography (CT)-guided stereobiopsy or from a craniotomy, we have described distinguishing cytologic features of some primary spontaneous nervous system tumors in 80 dogs and 13 cats. A final diagnosis was confirmed by evaluation of paraffin-embedded sections from the same sample and, when appropriate, by immunocytochemical staining. Preliminary findings indicate that, in dogs and cats, this procedure is useful for rapid, accurate intraoperative diagnosis of many primary nervous system tumors. The distinguishing features of the canine and feline tumors bear a remarkably close resemblance to their human counterparts. PMID- 11199165 TI - Evidence for the localization of porcine reproductive and respiratory syndrome virus (PRRSV) antigen and RNA in ovarian follicles in gilts. AB - The pathogenesis of porcine reproductive and respiratory syndrome virus (PRRSV) infection in ovary was studied in sexually mature, cycling, nonsynchronized gilts infected with the PRRSV 16244B, a virulent field strain. Previous studies have shown that PRRSV can be isolated from ovaries and is transplacentally passed from gilts to the fetuses. The cause of infertility following PRRSV infection is not known. In this study, we identified the tropism of PRRSV in ovarian tissue from experimentally infected gilts in samples collected between 7 and 21 days postinfection (DPI). Tissues were collected and examined by virus isolation, in situ hybridization (ISH), immunohistochemistry (IHC), and double labeling to identify PRRSV-infected cell types. PRRSV was isolated in ovarian follicles at 7 days DPI. The IHC and ISH indicated that PRRSV-positive cells in ovaries were predominantly macrophages, which were numerous in atretic follicles. No evidence of infection and/or perpetuation of PRRSV in ova was observed, indicating that the female gonad is an unlikely site of persistence. No alteration of the normal ovarian architecture that would support a possible role of PRRSV infection in porcine female infertility was observed. PMID- 11199166 TI - Periventricular changes associated with spontaneous canine hydrocephalus. AB - Causes of canine juvenile hydrocephalus have been well documented. However, the effects of hydrocephalus on periventricular white matter have been only partially described. The present report shows that hydrocephalus-associated lesions of the periventricular white matter, i.e., formation of diverticula, clefts, and tears, are prevalent. Marked hydrocephalus was identified at necropsy in 20 juvenile dogs between 1990 and 1999. The severity grade was based upon a ratio of lateral ventricular dimensions to cortical thickness. All animals exhibited ependymal lesions consisting of attenuation, with or without abortive attempts of ependymal regeneration, and ulceration. In 10 dogs (50%), unilateral or bilateral periventricular diverticula and cleft formation in the region of the caudate nucleus were observed. The diverticula were formed at the caudal pole of the caudate nucleus, communicated with the ventricular lumen, and were associated with ependymal denudation. Loss of the ependymal lining probably contributes to a bulk shift of cerebrospinal fluid from the ventricular lumen to the periventricular white matter, leading to diverticulum formation. Clefts were observed within the parenchyma at the border of the internal capsule and putamen, consistent with an ischemic insult. Occasionally tearing with separation of the caudate nucleus from the subcortical white matter was found, representing unification of expanding clefts and diverticula. In one of the few clinically well-documented cases, tearing was correlated with a sudden decline in neurologic function, culminating in euthanasia. However, tears and clefts may exhibit a chronicity of several days, as indicated by the presence of astroglial scars along the lesion margins. PMID- 11199167 TI - Viral replication and lesions in BALB/c mice experimentally inoculated with porcine circovirus isolated from a pig with postweaning multisystemic wasting disease. AB - Eight-week-old BALB/c mice were either sham inoculated (control mice) or were inoculated intraperitoneally (IP) and intranasally (IN) with a single (sPCV mice) or multiple (mPCV mice) doses of porcine circovirus 2 (PCV2). Four control mice and 4 sPCV mice were sacrificed 7, 14, 28, and 42 days postinoculation (PI). All 4 mPCV mice were sacrificed 42 days PI. In addition, 7-day and 14-day pregnant BALB/c mice were either sham inoculated (control mice) or were inoculated IP and IN with a single dose of PCV2. Newborn mice were euthanatized 1, 8, and 15 days after birth. Necropsies were performed on all euthanatized mice and tissues were collected for histopathology, electron microscopy, in situ hybridization, and polymerase chain reaction (PCR). PCV2 replicated in 8-week-old BALB/c mice that were inoculated with PCV2 and caused fetal infection when inoculated into pregnant BALB/c mice at 7 days and 14 days of gestation. PCV was detected by in situ hybridization and PCR in sPCV mice on days 7, 14, 28, and 42 PI; in mPCV mice on day 42 PI; and in newborn mice from mothers inoculated with PCV at 7 days and 14 days of gestation at 1, 8, and 15 days after birth, but not in control mice. No clinical signs or gross lesions were found in sPCV or mPCV mice during the study. Microscopic lesions in sPCV mice and mPCV mice were characterized by expansion of germinal centers in lymphoid organs with large numbers of histiocytic cells and lymphoblasts, apoptosis of histiocytic cells in germinal centers, and mild lymphoid depletion of the paracortex. PCV nucleic acid was detected in the nuclei and cytoplasm of histiocytes and apoptotic cells in germinal centers in lymphoid tissues as well as in the nuclei of hepatocytes in the liver, in the nuclei of renal tubular epithelial cells, and in the cytoplasm of single lymphocytes in the thymus. Congenitally infected mice only had PCV nucleic acid detected in putative Kupffer cells in livers. PMID- 11199168 TI - Canine model and genomic structural organization of glycogen storage disease type Ia (GSD Ia). AB - A canine model of glycogen storage disease Ia (GSD Ia), similar clinically, biochemically, and pathologically to the human disease, was established by crossbreeding Maltese and Beagle dogs carrying a mutated, defective glucose-6 phosphatase (G-6-Pase) gene. Ten puppies were born in three litters from these crossbreedings. Six were homozygous for the previously described M121I GSD Ia mutation. Of these six affecteds, two were stillborn, and one died at 2, 32, and 60 days of life, respectively (puppies A, B, C, D, E), while one is alive at age 15 months (puppy F). Affected puppies exhibited tremors, weakness, and neurologic signs when hypoglycemic. They had postnatal growth retardation and progressive hepatomegaly. Biochemical abnormalities included fasting hypoglycemia, hyperlactacidemia, hypercholesterolemia, hypertriglyceridemia, and hyperuricemia. Microscopic examination of tissues from affected puppies showed diffuse, marked hepatocellular vacuolation, with distended clear hepatocytes and central to marginally located rounded nuclei. In the kidneys of puppies D and E, there was segmental glomerular sclerosis and vacuolation of proximal convoluted tubular epithelium. Biochemical analysis revealed increased liver glycogen content and isolated markedly reduced G-6-Pase enzyme activity in liver and kidney. The canine G-6-Pase gene was characterized by screening a canine genomic library. It spans approximately 11.8 kb and consists of five exons with >90% amino acid sequence homology to the derived human sequence. The first 1.5 kb of the 5' region was sequenced and contains several putative response element motifs homologous to the human 5' region. Establishment of this canine colony of GSD Ia that closely resembles human disease and isolation of the canine genomic gene provides an excellent model for studying pathophysiology and long-term complications and an opportunity to develop novel therapeutic approaches such as drug and gene therapy. PMID- 11199169 TI - Physeal dysplasia with slipped capital femoral epiphysis in 13 cats. AB - Separation of the femoral capital epiphysis is associated with severe trauma in most species. This report describes 13 cats with slipped capital femoral epiphysis characterized by a distinctive lesion in the physeal cartilage. The lesion consists of irregular clusters of chondrocytes separated by abundant matrix on both the epiphyseal and metaphyseal side of the cleavage site. The affected population in this study is 85% male, 90% overweight, 23% Siamese, and 4.5-24 months old. The histopathology and demographics are similar to slipped capital femoral epiphysis in humans, which most often affects overweight adolescent boys. PMID- 11199170 TI - Origin of enzootic intranasal tumor in the goat (Capra hircus): a glycohistochemical approach. AB - Enzootic intranasal tumor (EIT) appears glandular in type and has recently been classified as an adenocarcinoma of low malignancy. The aim of this study was to characterize the secretion of surface glycoconjugates (GCs) in EIT and in normal respiratory and olfactory mucosae of the goat by means of conventional and lectin histochemistry, in order to shed light on the histogenesis of EIT. Morphologic and ultrastructural investigations showed two growth types of EIT: i.e., tubular and papillary patterns. Conventional histochemistry revealed the presence of neutral and carboxylated GCs in the olfactory glands and in the tubular part of EIT, as well neutral and sulphated GCs in the respiratory glands and in the papillary part of EIT, suggesting that the papillary pattern tumor arises from the respiratory glands, whereas the tubular portion of EIT arises from the olfactory glands. Lectin histochemistry gave further information on the expressed GCs. PMID- 11199171 TI - [Temporary work disability among firemen employed in rescue and fire brigades]. AB - Workers of rescue and fire brigades participating in actions are exposed to harmful effect of toxic substances, chemicals or physical factors. They also experience enormous emotional shock evoked by direct threat or contact with victims of disasters and fires. The aim of the study was to define the pathology which increases the risk of temporary work disability among firemen. The study covered 150 firemen employed during the years 1994-97 in rescue and fire brigades selected at random. The data on the number of days and cases of work disability during the period of four years for each firemen covered by the study were analysed. In the group under study a mean annual number of work disability due to sickness accounted for 1443 days per 100 employed. The major causes of work disability were as follows: diseases of the respiratory system (22% of total sickness absenteeism); diseases of the nervous system and sense organs (19%); diseases of the musculoskeletal system (18%), diseases of the circulatory system (13%); mental disorders (8%); and diseases of digestive system (7%). Sickness absenteeism among workers of rescue and fire brigades was lower by 30% on average than that among men employed in the national economy. But in the 50-59 age group, it was higher by 68%. In this age group, the highest level of sickness absenteeism was associated with mental disorders (15 times higher than in other male occupational groups); diseases of the musculoskeletal system (higher by 53%); diseases of the respiratory system (2 times higher); neoplasms (7 times higher); diseases of the nervous system (higher by 46%). It should be stressed that the study revealed increased work disability due to lung (by 33%), bladder (6 times higher) and brain (over 3 times higher) cancers. The results of this study find their confirmation in many other epidemiological studies of this occupational group. PMID- 11199172 TI - [Mortality in the tire plant workers]. AB - This paper describes a cohort study of the mortality among workers employed in one of Polish tyre plants. The scope of the study was limited to the analysis of mortality from main disease categories. Mortality from particular cancer sites will be discussed in a separate publication. The cohort comprised 17,747 workers (11,660 men and 6,087 women) employed during the years 1950-95 for at least three months in the tyre plant. As of 31 December 1995, the follow-up of the cohort was completed. A detailed analysis of mortality by causes was carried out using standardised mortality ratio (SMR) calculated by the person-years method. The general population of Poland was used as the reference. The results indicated general mortality significantly lower in the cohort (men: SMR = 72; women: SMR = 62), than in the reference population. The number of observed deaths from main disease categories was also lower than those expected. The analysis by specific causes revealed significant excess of deaths, due to hypertensive disease among men (36 deaths, SMR = 142; 95% CI: 99-197). SMRs were also calculated in sub cohorts identified by activities performed (preparatory works: production of tyres and inner tubes; maintenance; storage; others). General mortality in sub cohorts was similar to that in the total cohort. After analysis by causes of death, some non-significant excess mortality could be observed. It was very small or it applied only to single cases of death. Excess mortality from hypertensive disease in male maintenance workers (21 deaths, SMR = 262; 95% CI: 162-400) was the only exception. The absence of adverse health effects pronounced by significant excess mortality should be attributed to a relatively short period of exposure among the majority of the followed-up workers (over 58% of workers in the cohort employed in the plant for a period shorter than five years) and to their young age. Almost 56% of workers in the cohort were born in the 1950s or later which means that at the end of the follow-up they were not older than 45 years. In order to complete the final mortality assessment the follow-up should continue. PMID- 11199173 TI - [Function of dopamine in mesenteric blood vessels of rats poisoned with lead and cadmium]. AB - The aim of this study was to evaluate the impact of combined exposure to lead and cadmium, used in hypertensive doses, on the reactivity of isolated mesenteric rat vessels to dopamine. Experiments were performed on 64 male Buffalo rats (195-245 g body weight) administered intragastrically with lead acetate (35 mg Pb/kg b.w.) and/or cadmium chloride (5 mg Cd/kg b.w.) once a week for seven weeks. The isolated mesenteric bed was prepared according to McGregor's method. Dopamine (800 micrograms) was injected before and during the infusion, one after the other, of angiotensin converting enzyme (0.0004 j/ml/min), ketoprofen (0.2 mg/ml/min), and losartan (0.05 mg/ml/min) or infusion of nitric oxide synthase blocker, N-omega-nitro-L-argine (22 micrograms/ml/min), verapamil (0.001 mg/ml/min), and then propranolol (0.3 mg/ml/min). The results show an unchanged, in comparison to controls, vascular effect of dopamine in lead and cadmium poisoned rats. However, these metals modified the reactivity of mesenteric vessels to endogenous angiotensin and prostaglandins mediated pressor action of dopamine. PMID- 11199174 TI - [Use of the ACSL simulation language for physiologic toxicokinetic models]. AB - For the description of the processes of absorption, excretion or elimination of chemicals, the open one- or two-compartment models have been used thus far. The latter consist mainly of the fast (central) and slow (peripheral) compartments. The toxicological studies were based on an assumption that the organic processes develop according to is the first order kinetic reaction. However, the absorption, elimination or excretion of toxic chemicals are in fact much more complicated processes that should be explained using, e.g. the physiologically based toxicokinetic (PBTK) models, covering physiological, biochemical and metabolic parameters, as well as the allometric calibration of selected parameters for interspecies extrapolations, and in vitro/in vivo extrapolations of metabolic parameters. Simulation languages, e.g. ACSL (Advanced Continuous Simulation Language) are indispensable application tools to be operated with PBTK models. They have been developed for modelling systems described by time dependent non-linear differential equations and/or transfer functions. ACSL with its interfaces (ACSL Builder, ACSL Graphic Modeller, ACSL Math) ensures data input and communication inside the model by the control, transfer and computed parameters. The physiologically-based toxicokinetic models employ a large number of different parameters, which enables, e.g. forecasting the dose/effect or dose/response relationship absorption rate, metabolic pathways, excretion or elimination according to the absorbed dose of xenobiotic; evaluation of risk assessment; extrapolation from high to low doses characteristic of environmental exposure or setting biological exposure limits. PMID- 11199175 TI - [Irritating effect and dermal toxicity of virkon, a disinfectant widely used in Poland]. AB - The aim of the study was to define the threshold irritating effect of Virkon, a disinfectant widely used in Poland, on the rabbit's skin and eye, and its dermal toxicity in single exposure. The studies were carried out according to the OECD guidelines, modified by Krysiak. A 10% aqueous solution of Virkon in the conditions of multiple open exposure was defined as the threshold concentration evoking small inflammatory reaction. After a single administration of Virkon in aqueous solutions into the rabbit's eye, the value of sensitising effect index was 1.5 for 1% solution of the disinfectant in question which indicates weak inflammatory reaction. The study of dermal toxicity in a single exposure revealed neither animal death nor morphological changes in internal organs which suggests non-cutaneous absorption of Virkon. The present study may provide the basis for assessing dermatological changes in people exposed to disinfectants. PMID- 11199176 TI - [The fibrogenic effect of artificial ceramic fibres in experimental rats]. AB - The fibrogenic effect of aluminosilicate ceramic fibres in rats administered intratracheally with a single dose of 25 mg was assessed on the basis of the lung hydroxyproline concentration and morphological changes in the lung parenchyma and mediastinum lymphatic nodes. Control groups were composed of rats administered with NaCl saline and crocidolite UICC. The rats were exposed for 6 and 9 months. It was found that after 6 and 9 months, aluminosilicate ceramic fibres (L-1, Langfaser, Thermowool and Kaowool) showed weak fibrogenic properties. The range of changes in reactivity, and the presence of fibres of fibrous connective tissue in granulomas, induced by ceramic fibres were lower than the range of changes and the contribution of connective tissue produced by asbestos and crocidolite UICC. PMID- 11199177 TI - [Efficacy of vaccination against influenza among working people--results of epidemiological studies]. AB - Influenza among working people is responsible for the enhanced sickness absenteeism, limited work capacity and efficiency, as well as for the increased health service demand. The efficacy of vaccination against influenza has been assessed most frequently on the basis of clinical symptoms without taking virological tests to confirm the presence of virus in the patients' serum. According to current epidemiological studies on the occurrence of the influenza like symptoms, the efficacy of vaccination usually range between 18.3-23%. However, values reaching 54% or even 88% have also been noted. Only a few single studies did not show significant effects of vaccination against influenza. Savings due to vaccination have ranged from several to 20, and in one study even to 46 dollars per one vaccinated worker. These economic differences should be mainly attributed to the differences in the structure of direct and indirect costs taken into account. The direct costs depend, to a great extent, on whether savings due to the number of visits not attended by patients who had been vaccinated and thus, not suffered from flue, as well as the costs incurred in vaccination-promoting programmes and their implementation by nurses have been taken into account. In the structure of indirect costs, the largest difference was noted in regard to savings due to not wasted working time. These savings ranged from 9.9 dollars per one worker in Poland to 52.87 dollars in Canada. The range of savings obtained depends on the index of workers' participation in the vaccination programme, and this index is usually a derivative of the input of resources into the promotion of such kind of health conducive behaviour. It seems that in view of preliminary positive results of the economic assessment, the employers will encourage their workers to undergo preventive vaccination against influenza. It may be expected that appropriate promotion actions of much wider scope will be undertaken that will contribute to the increased number of vaccinated workers. However, the final decision in this respect will always depend on the worker's good will. PMID- 11199178 TI - [Effect of arsenic and its compounds on the circulatory system]. AB - Arsenic is a metal which occurs widely in both occupational and physical environments. Therefore, its easy accessibility and high toxicity raise the question on whether arsenic, particularly in relatively small doses, can cause damage of relevant molecular, biochemical and clinical significance to the cardiovascular system. The present review is focused on the confirmed and potential mechanisms of arsenic effect on the function and structure of vascular endothelium (nitric oxide, peroxynitrite), its role in stimulating the oxidative species formation (hydroxyperoxide, superoxide and lipid peroxide formation), as well as in decreasing the antioxidative response (enzymes: superoxide dysmutase, catalase, glutation peroxidase), its cytotoxic effects, including immunotoxic properties, arsenic action in the signal transduction pathways network (kinases and DNA transcription factors), impact on cell proliferation, differentiation and apoptosis, not to mention its interference with DNA synthesis and repair processes. Apart from mechanisms of arsenic action, the article provides the up to-date information on various cardiovascular diseases of the established or presumed arsenic origin. PMID- 11199179 TI - [Problems faced in hygiene evaluation of Welders' working conditions--analysis of chemical hazards]. AB - Dissemination of individual welding methods, as well as assessment of welding fume and gas emissions and their physical properties, chemical composition and related difficulties in hygiene evaluation of working conditions are discussed. PMID- 11199180 TI - [Electromagnetic diagnostic and therapeutic equipment--patient and medical personnel exposure to electromagnetic fields]. AB - The mechanisms responsible for the interaction between electromagnetic fields and the biological matter were reviewed. For each of the mechanisms one or more relevant diagnostic and/or therapeutic methods were applied. The characteristics of exposure to electromagnetic fields generated by individual types of medical equipment among the diagnosed or treated subjects, as well as the magnitude of exposure observed in the medical personnel are present. PMID- 11199182 TI - 8th Meeting of the European Society of Gene Therapy (ESGT). Stockholm, Sweden, 7 10 October 2000. Abstracts. PMID- 11199181 TI - [Assurance and assessment of quality education in occupational medicine in selected countries of western Europe and in the United States. 1. Western Europe]. AB - The author discusses the studies undertaken with the general aim to provide education in occupational medicine and assure and assess its quality in some countries of Western Europe advanced more than Poland in this area. It becomes quite evident that despite a widespread interest in quality of education, there is a lack of basic systemic solutions. A gap between basic theoretical and methodological guidelines and a large number of dispersed reports on concrete analytical and evaluation studies can be still observed. In addition to the presentation of an inside view of research activities carried out in some countries of Western Europe and the United States, based on selected professional publications, the author formulates general conclusions on how the assurance and quality assessment of education in occupational medicine function in those countries. PMID- 11199183 TI - Internet-based strategies in teaching and research. PMID- 11199184 TI - Determinants of bone mineral density in older men. AB - Although osteoporosis in men is increasingly recognized as an important health issue and bone mass appears to be a major determinant of fracture, there remain few data concerning the determinants of bone mass in men. To determine the correlates of bone density in men, we studied a large group of older subjects recruited from three rural communities in the northwestern United States. Three hundred and fifty-five men over the age of 60 years (mean 71.5 +/- 7.4 years) without known disorders of mineral metabolism were recruited by community advertising. Bone mineral density was measured at the lumbar spine, proximal femur and radius by dual-energy X-ray absorptiometry, and factors potentially related to skeletal status were assessed by direct measurements or questionnaire. In univariate analyses weight (positively) and age (negatively) were associated with bone density. After adjustment for these two factors, alcohol intake, osteoarthritis and thiazide use were associated with higher bone density, while previous fractures, gastrectomy, peptic ulcer disease, rheumatoid arthritis, glucocorticoid use, hypertension, previous hyperthyroidism, height loss since age 20 years, chronic lung disease and smoking were related to lower density. In multivariate models, only weight and a history of cancer were related to higher bone mass, and age, previous fracture, rheumatoid arthritis, gastrectomy and hypertension were associated with lower density. These data contribute to the emerging field of osteoporosis in men, and may help in the clinical identification of men at higher risk of osteopenia. PMID- 11199185 TI - The injury mechanisms of osteoporotic upper extremity fractures among older adults: a controlled study of 287 consecutive patients and their 108 controls. AB - The risk factors for falls in older adults are well known but knowledge on the direct injury mechanisms that result in various osteoporotic fractures has been very sparse. The purpose of this study was therefore to clarify the injury mechanisms of osteoporotic upper extremity fractures of older adults and to compare these mechanisms with those of the control fallers, and in this way to obtain reliable insight into the etiology and pathogenesis of upper extremity fractures and thus to enable fracture prevention. One hundred and twelve patients with a fresh fracture of the proximal humerus, 65 patients with an elbow fracture, 110 patients with a wrist fracture and 108 controls (no fracture, or a fracture other than the case fracture) were interviewed and examined between September 1995 and December 1997. The inclusion criteria of the subjects were that the patient was 50 years of age or older at the time of the accident, and that the fracture/injury had occurred as a result of low-energy trauma (typically a fall from standing height or less) within a week before the interview and examination. In 97% of patients with a proximal humerus or elbow fracture, and in all patients (100%) with a wrist fracture, the fracture was a result of a fall. In the control group this figure was 93%. In a polychotomous logistic regression analysis the intergroup differences in the fall directions (adjusted by gender, age and functional capacity) were statistically highly significant (chi 2 = 43.6, d.f. = 15, p < 0.001). Most of the patients with a proximal humerus fracture or elbow fracture reported that they had fallen 'obliquely forward' (43% and 38%) or 'to the side' (29% and 26%), whereas in the wrist fracture group the main fall direction was also 'obliquely forward' (34%) but the other fall directions (i.e., 'forward', 'to the side', 'obliquely backward' and 'backward') were quite equally represented (13-19%). The odds ratio (OR) for an obliquely forward fall resulting in a proximal humerus fracture was 3.5 [95% confidence interval (CI) 1.4-9.2), as compared with the fall directions of the controls and the 'obliquely backward' fall direction. In a logistic regression analysis the patients with a wrist fracture managed to break their fall (e.g., with an outstretched arm) more frequently than the patients in the other groups (OR 3.9; 95% CI 2.0-7.3). The patients with a proximal humerus fracture, in turn, managed to break their fall less frequently than the controls (OR 0.33; 95% CI 0.14-0.80). The same was true of the patients with an elbow fracture, although the difference was not significant (OR 0.49%; 95% CI 0.19-1.3). As objective evidence for a direct fall induced impact on the fracture site, 68% of patients with a proximal humerus fracture revealed a fresh subcutaneous hematoma on the shoulder/upper arm, while such a hematoma was rare in the controls (2%) (p < 0.001). Correspondingly, 62% of patients with an elbow fracture showed a similar hematoma on the elbow area, while this was seen in none of the controls (p < 0.001). In patients with a wrist fracture a hand/wrist hematoma was seen in 58% of the victims, as compared with 18% of the controls (p < 0.001). The study shows that the most typical osteoporotic upper extremity fractures of older adults have their specific injury mechanisms. A great majority of these fractures occur as a result of a fall and a subsequent direct impact of the fractured site. Effective fracture prevention could be achieved by minimizing the obvious risk factors of falling and reducing the fall-induced impact force with injury site protection. PMID- 11199186 TI - The effect of weight change on total body dual-energy X-ray absorptiometry: results from a clinical trial. AB - In the past decade dual-energy X-ray absorptiometry (DXA) scanning has assumed an important role in the evaluation of new treatments for osteoporosis. Although the spine and hip are the sites usually chosen for monitoring bone mineral density (BMD) changes, total body DXA is also of interest because of the comprehensive view it gives of the whole skeleton. However, recent studies have reported anomalies in total body DXA in subjects undergoing weight change, suggesting that the technique may not be valid in this circumstance. The present study evaluated total body DXA in a trial of cyclical etidronate therapy in which many subjects underwent significant weight change. The study population was 152 postmenopausal women who had spine, hip and total body DXA scans performed at baseline, 1 and 2 years. The total body scans were analyzed using two software options referred to as 'standard' and 'enhanced'. The following variables were studied: total body BMD, total body bone mineral content (BMC), and subregional BMD values for the following seven sites: lumbar spine, thoracic spine, pelvis, head, ribs, arms and legs. The percentage change from baseline was analyzed in a multivariate regression analysis to derive the treatment effect (defined as the difference in changes between the etidronate and placebo groups) and a coefficient that described the effect of weight change on the total body DXA variable. Mean weight change after 2 years was +1.1 kg (range -9.3 to +16.8 kg). Results for the weight change coefficient were significantly different from zero for five of nine total body variables using the standard analysis and seven of nine for the enhanced analysis with values (and standard errors) that varied from +0.67 (0.04)%/kg for standard total body BMC to -0.32 (0.11)%/kg for enhanced arm BMD. Results for the treatment effect at 2 years were significantly different from zero for total body BMD, total body BMC and for the lumbar spine, thoracic spine and pelvis BMD subregions, but were not significant for head, rib, arm or leg BMD. Findings for the standard and enhanced analyses agreed closely and the size of the treatment effect was related to the proportion of trabecular bone at the measurement site. We conclude that in a randomized study the effects of weight change can be corrected and total body DXA can give useful information about the response to treatment across the whole skeleton. PMID- 11199187 TI - Prediction of bone strength from cancellous structure of the distal radius: can we improve on DXA? AB - Recent studies show that structural parameters of bone, obtained from computerized image analysis of radiographs, can improve the noninvasive determination of bone strength when used in conjunction with bone density measurements. The present study was designed to assess the ability of image features alone to predict the mechanical characteristics of bones. A multifactorial model was used to incorporate simultaneously a number of characteristics of the image, including periodicity and spatial orientation of the trabeculae. Fifteen pairs (29 specimens) of unembalmed human distal radii were used. The cancellous bone structure was determined using computerized spectral analysis of their radiographic images and the bones were tested to failure under compression. Multilayered perceptron neural networks were used to integrate the various image parameters reflecting the periodicity and the spatial distribution of the trabeculae and to predict the mechanical strength of the specimens. The correlation between each of the isolated image parameters and bone strength was generally significant, but weak. The values of mechanical parameters predicted by the neural networks, however, had a very high correlation with those observed, namely 0.91 for the load at fracture and 0.93 for the ultimate stress. Both these correlations were superior to those obtained with dual-energy X-ray absorptiometry and with the cross-sectional area from CT scans: 0.87 and 0.49 respectively. Our observation suggests that image parameters can provide a powerful noninvasive predictor of bone strength. The simultaneous use of various parameters substantially improved the performance of the system. The multifactorial architecture applied is nonlinear and possibly more effective than traditional multicorrelation methods. Further, this system has the potential to incorporate other non-image parameters, such as age and bone density itself, with a view to improving the assessment of the risk of fracture for individual patients. PMID- 11199188 TI - Osteocalcin gene polymorphism is related to bone density in healthy adolescent females. AB - Recently a polymorphism was found in the human osteocalcin gene, and its association with bone mass was investigated in healthy postmenopausal Japanese women. The osteocalcin gene allelic variant HH was found to be overrepresented in women with osteopenia. The purpose of this study was to investigate whether the previously demonstrated polymorphism of the osteocalcin gene was related to bone mineral density (BMD; g/cm2) or osteopenia in a group of 97 healthy Caucasian adolescent females (aged 16.9 +/- 1.2 years, mean +/- SD). BMD of the left humerus, right femoral neck, lumbar spine and total body was measured using dual energy X-ray absorptiometry. The relation between the allelic variants and bone density was analyzed as presence or absence of the H allele. Presence of the H allele was found to be related to a lower BMD of the humerus (0.97 vs 1.02, p = 0.03). There was also a strong tendency towards significance at the femoral neck (p = 0.06) and total body (p = 0.11). Using a multiple linear regression and including physical activity, weight, height and years since menarche, presence of the H allele was found to be an independent predictor of humerus BMD (beta = 0.21, p < 0.05) and femoral neck BMD (beta = -0.23, p < 0.01). Using logistic regression, presence of the H allele was also independently associated with a 4.5 times increased risk of osteopenia (p = 0.03) in the whole group. Osteopenia was defined as at least 1 SD lower bone density than the mean for the whole group of at least one of the BMD sites measured. We have demonstrated that the osteocalcin HindIII genotype is independently related to bone density in healthy adolescent females. The present study also suggests that presence of the H allele is predictive of osteopenia at an early age. PMID- 11199189 TI - Site-specific variation in the classification of osteoporosis, and the diagnostic reclassification using the lowest individual lumbar vertebra T-score compared with the L1-L4 mean, in early postmenopausal women. AB - In this study we report first the concordance and variation in diagnostic osteoporosis classification using multiple skeletal site measurements compared with the lumbar spine only; and secondly, at the lumbar spine, the variation and diagnostic osteoporosis reclassification using the lowest individual vertebra T score compared with the L1-L4 mean T-score. One hundred and fifty early postmenopausal women were evaluated as part of the recruitment for a multicenter osteoporosis prevention study. Bone mineral density (BMD) was restricted such that no more than 10% of the subjects had a lumbar spine BMD below 0.8 g/cm2. Forty-seven per cent of the subjects were classified as having low bone mass (T score < or = -1.0) at the lumbar spine, 63% at the mid-forearm, 39% at the distal forearm and 50% at the hip (p < 0.05). The greatest proportion of subjects were categorized as osteoporotic at the lumbar spine, followed by the forearm and then the hip. Correlation between sites ranged from 0.57 to 0.60 (p < 0.01). Eighty one percent of the subjects had a significant difference between their highest and lowest individual lumbar vertebra T-score (defined as a difference outside the 90% confidence interval coefficient of variation T-score value). Using the lowest individual lumbar T-score, recategorized 33% of the subjects classified as osteopenic (based on the mean L1-L4 T-score) as osteoporotic, and 23% of those classified as normal as osteopenic (p < 0.05). Of all four vertebrae, L2 had the highest T-score in 37.7% of the subjects (mean -0.3) and L4 the lowest in 61% (mean -1.5) (mean difference 1.2 units, 95% CI 0.7 to 1.7). The classification of osteoporosis varies according to skeletal site, with pronounced differences in the early menopausal population. T-scores are useful for characterizing subjects with the highest risk of osteoporosis but BMD and fracture risk must be recognized in a continuum. Individual T-scores of the lumbar vertebrae show wide variation in the absence of degenerative spinal disease or vertebral collapse and the use of the lowest, significantly different, individual lumbar vertebra T score reclassified over half of the subjects in this study. This poses a great therapeutic dilemma in clinical practice, particularly if these fractures are at higher risk of future collapse. PMID- 11199190 TI - Reference data of forearm bone mineral density in healthy Japanese male and female subjects in the second decade based on calendar age and puberty onset: Japanese Population Based Osteoporosis (JPOS) study. AB - Osteoporosis is a major public health problem in Japan. The second decade is an important period in which to attain a high peak bone mass. However, normal values of forearm bone mineral density (BMD) are not well known in children and adolescents. BMD at one-third of forearm length proximal to the ulnar end plate (BMD1/3) and the ultradistal forearm (BMDud) was measured using dual-energy X-ray absorptiometry (DXA) in 1207 (631 males, 576 females) Japanese subjects aged 9-18 years. Puberty onset was assessed by questionnaire, by obtaining the time that pubic hair appeared in males and the time that menstruation started in females. BMD1/3 and BMDud increased steadily with age in males. In relation to puberty development, these parameters also increased after puberty onset although the increase in BMD1/3 was not statistically significant after the fifth year from puberty onset and that of BMDud was not significant after the sixth year from puberty onset. BMD1/3 and BMDud increased with age and then plateaued in females. The increase in BMD1/3 was not statistically significant after 15-16 years of age and that of BMDud was not significant after 13-14 years of age. In relation to puberty development, the increase in BMD1/3 leveled out after the fourth year from puberty onset and that of BMDud also plateaued after the third year from puberty onset. We provide reference values of forearm BMD in Japanese children and adolescents by DXA according to calendar age and puberty development. Peak bone mass of the forearm may be in the late second decade in Japanese females. PMID- 11199191 TI - Bone mineral density, hip axis length and risk of hip fracture in men: results from the Cornwall Hip Fracture Study. AB - Bone mineral density (BMD) and hip axis length (HAL) are important determinants of fracture risk in women. There are, however, few data concerning their predictive risk in men. The aim of this study was to determine the relationship between BMD, HAL and the risk of hip fracture in men. A case-control design was used. Cases were men aged 50 years and over with a minimal-trauma hip fracture admitted to the Royal Cornwall Hospital, Truro, during 1995-1997. Controls were recruited from a large general practice within the catchment area of the hospital. Subjects were invited for assessment of BMD at the lumbar spine and proximal femur, using dual-energy X-ray absorptiometry. HAL was assessed using machine software. Data concerning BMD were available in 62 fracture cases and 100 controls. After adjusting for age, height and weight, a reduction in BMD was associated with a significant increase in the risk of hip fracture [odds ratio (OR) 1.8-4.0 per standard deviation (SD) reduction, depending on site]. HAL was similar in both fracture and control groups (12.0 cm vs 12.0 cm). After adjusting for height, there was no association between HAL and the risk of hip fracture (OR per 1 SD increase in HAL = 0.9; 95% confidence interval 0.6, 1.3). Compared with those with a cervical fracture (n = 31), those with an intertrochanteric fracture (n = 31) had lower BMD at all skeletal sites, though this was significant for the trochanteric site only. It is concluded that BMD though not hip axis length is a risk factor for low-trauma hip fracture in Caucasian men. PMID- 11199192 TI - Three-dimensional modeling of the effects of parathyroid hormone on bone distribution in lumbar vertebrae of ovariectomized cynomolgus macaques. AB - Biomechanical and quantitative computed tomography (QCT) analyses showed beneficial effects of parathyroid hormone (PTH (1-34)) on lumbar vertebrae from ovariectomized monkeys, even after withdrawal of treatment for 6 months. Adult cynomolgus monkeys were randomized, ovariectomized (except for sham ovariectomy controls), and treated subcutaneously with vehicle (OVX) or 5 micrograms/kg per day PTH (1-34) (PTH5) for 18 months. An additional group was treated subcutaneously with 5 micrograms/kg per day PTH (1-34) (PTH5W) for 12 months and then switched to vehicle for the remaining 6 months. Lumbar vertebrae were excised at necropsy, and L5 were serially scanned by QCT, using 70 x 70 x 500 microns voxels. PTH increased volumetric bone mineral density (BMD, mg/cm3) and bone mineral content (BMC, mg) for both PTH5 and PTH5W compared with OVX and Sham without inducing hypermineralization, without stimulating periosteal expansion, and without significant constriction of the neural canal. BMD values for the voxels were then averaged to create nearly isotropic voxels of 490 x 490 x 500 microns. Serial scans were stacked and a triangular surface mesh generated for each bone, using a 'marching cubes' algorithm. A smoothed version of each surface mesh was used to generate a tetrahedral element for three-dimensional finite element modeling. An isotropic Young's modulus for each tetrahedral element was calculated as a function of the original voxel BMDs. Linear elastic stress analysis was then performed for each finite element model in which a distributed load of 100 newtons (N) was applied to the top surface of the centrum, perpendicular to the bottom surface with the bottom surface constrained in the direction of loading. Analysis of the effective strain showed considerable reduction in vertebral strain for both PTH5 and PTH5W, compared with OVX. Compression testing of the adjacent L3 and L4 confirmed that vertebral strength and stiffness for PTH5 and PTH5W were significantly greater than for OVX. Histogram and QCT analyses showed PTH conversion of low-density bone (trabecular bone) into medium-density bone (more and thicker trabeculae) by stimulating bone apposition. PTH withdrawal induced conversion of medium-density into low-density and high-density bone with the latter higher than in OVX. These data show that even transient PTH treatment improves vertebral architecture and bone quality to reduce the likelihood of fracture, and that transient treatment is better than no PTH treatment at all. PMID- 11199193 TI - In elderly women weight is the best predictor of a very low bone mineral density: evidence from the EPIDOS study. AB - Currently, few elderly women have a measurement of bone mineral density (BMD). The aim of this study was to assess the potential value of a two-step screening process to identify the elderly women who are at greatest risk of fracture because of very low BMD: (1) use simple clinical criteria to select women who are highly likely to have a very low BMD and (2) measure the BMD of the women so selected. We used baseline data from 6958 women aged 75 years or older who were participants in the EPIDOS prospective study of risk factors for hip fracture. The outcome variable was very low BMD measured at the femoral neck by dual-energy X-ray absorptiometry and defined as a T-score < or = -3.5. The factors most predictive of very low BMD were low weight, history of fracture after the age of 50 years, slow gait, balance impairment, low grip strength, and dependence for instrumental activities of daily living. A score based on the risk function including these factors has a sensitivity of 80% at the median cut-off. Hence, by measuring the BMD of only half the population, 80% of the women with very low BMD can be identified. Weight is the strongest determinant of very low BMD and has approximately the same sensitivity as the complete score. In conclusion, a risk score for very low BMD based on simple criteria such as weight could be a useful clinical tool to select elderly women for bone densitometry. PMID- 11199195 TI - Estimation of the prevalence of low bone density in Canadian women and men using a population-specific DXA reference standard: the Canadian Multicentre Osteoporosis Study (CaMos). AB - The Canadian Multicentre Osteoporosis Study (CaMos) is a prospective cohort study which will measure the incidence and prevalence of osteoporosis and fractures, and the effect of putative risk factors, in a random sample of 10,061 women and men aged > or = 25 years recruited in approximately equal numbers in nine centers across Canada. In this paper we report the results of studies to establish peak bone mass (PBM) which would be appropriate reference data for use in Canada. These reference data are used to estimate the prevalence of osteoporosis and osteopenia in Canadian women and men aged > or = 50 years. Participants were recruited via randomly selected household telephone listings. Bone mineral density (BMD) of the lumbar spine and femoral neck were measured by dual-energy X ray absorptiometry using Hologic QDR 1000 or 2000 or Lunar DPX densitometers. BMD results for lumbar spine and femoral neck were converted to a Hologic base. BMD of the lumbar spine in 578 women and 467 men was constant to age 39 years giving a PBM of 1.042 +/- 0.121 g/cm2 for women and 1.058 +/- 0.127 g/cm2 for men. BMD at the femoral neck declined from age 29 years. The mean femoral neck BMD between 25 and 29 years was taken as PBM and was found to be 0.857 +/- 0.125 g/cm2 for women and 0.910 +/- 0.125 g/cm2 for men. Prevalence of osteoporosis, as defined by WHO criteria, in Canadian women aged > or = 50 years was 12.1% at the lumbar spine and 7.9% at the femoral neck with a combined prevalence of 15.8%. In men it was 2.9% at the lumbar spine and 4.8% at the femoral neck with a combined prevalence of 6.6%. PMID- 11199194 TI - Quantitative computed tomography in the evaluation of spinal osteoporosis following spinal cord injury. AB - Disuse osteoporosis occurs in the lower extremities of patients with spinal cord injury (SCI). However, spinal osteoporosis is not usually observed in these patients. We investigated lumbar spine bone mineral density (BMD) in SCI patients using single energy quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA). Our study population consisted of 64 patients with long standing SCI. Spine BMD (g/cm3) was assessed by QCT at four vertebrae ranging from T11 to L4 with single mid-vertebral CT slices 1 cm thick parallel to the vertebral end-plates. Confounding variables affecting normal trabecular bone pattern, such as compression fractures, surgical hardware or fat replacement, were excluded. For a subset of 29 patients, DXA values of the spine and femoral neck were also measured, and QCT and DXA Z-scores were compared On the average, the 64 SCI patients had Z-scores 2.0 +/- 1.2 below those of age-matched controls. In the subset of 29 patients with both QCT and DXA measurements, the QCT and DXA Z-scores were 2.4 +/- 1.1 below and 1.3 +/- 2.3 above the mean, respectively (p < 0.0001). Our results indicate that QCT reveals osteoporosis of the spine after SCI, in contrast to DXA. We postulate that QCT is more valuable for evaluating spinal osteoporosis following SCI than DXA and thus recommend QCT for spinal BMD studies in SCI. PMID- 11199196 TI - 2nd International Meeting on Social and Economic Aspects of Osteoporosis and Bone Diseases. 7-9 December 2000, Liege, Belgium. Abstracts. PMID- 11199197 TI - [Health, public health, society--results from the past, responsibilities for the future]. AB - Communication is the basic precondition of a global society. At the same time, however, communication is a basic cause for today's health hazards and diseases. This is an experience of our time, it is a historical experience of social change as well. If a global society wants to survive, the existing hazards to life and health have to be understood and treated on a global scale. Apart from a "new morbidity" and chronic diseases also infectious diseases again require more and more attention even in industrialised countries. The history of public health offers an overwhelming expertise of well-established concepts for every imaginable risk, to handle infectious diseases which are either not yet or no longer controllable on an individual therapeutical level. History of medicine also shows, that the effectiveness of hygienic concepts is based on their scientific validity and the resulting predictability of their interventions. This implies, that modern hygiene has to incorporate actively the concept of molecular medicine. Every single discipline involved, i.e. hygiene/sanitation, toxicology, microbiology, bacteriology, immunology, and infectiology, has to join in interdisciplinary scientific and interventional efforts. PMID- 11199198 TI - [Inpatient management of children and adolescents with psychiatric diseases in Germany]. AB - Employing official statistics from the year 1997 the present article analyses in patient treatment of children and adolescents with psychological disorders in all 16 German Bundeslaender. Sixty per cent of the children and adolescents who are referred to and treated in a German clinic for psychological disorders on the basis of a psychiatric diagnosis are not given professionally adequate treatment. Furthermore, evidence is presented documenting inpatient treatment of children only 0 to 12 months of age in clinics throughout Germany on the basis of psychiatric diagnoses. A new measure is introduced for future planning of inpatient health care for children and adolescents with psychological disorders in Germany. PMID- 11199199 TI - [DRGs in psychiatric hospital financing exemplified by Hungary. A model for Germany?]. AB - One of the most important provisions incorporated in the reform of the German health sector has been the introduction of a per case prospective payment system for hospitals with the exception of admissions to psychiatric care. The reasons for the exclusion of psychiatric care are unclear, but it is as a result all the more interesting to look at the experience of Hungary, where in-patient psychiatric care has been financed on the basis of diagnosis-related groups (DRGs) for the past seven years. The article describes how in the early 1990's the funding of the Hungarian health service was reorganized from being a state financed system with a set budget to a system financed by contributions. Parallel to this development, service-related financing was introduced. In the hospital sector this involved DRGs. At the beginning of 1993 the Hungarian DRGs comprised only 437 categories, but this has since increased to 758. Furthermore, other characteristics are listed which, apart from the number of groups, differentiate the Hungarian DRGs from the AP-DRGs. Among other things, service-related financing includes non-typical areas such as psychiatry. In this case, it covers in-patient psychiatric care in an unusual combination of DRGs in the acute case category (50% of all beds in psychiatric units in Hungary are for acute cases) with daily nursing charges in the chronic case category. An analysis is given in the article of 16 homogeneous diagnostic categories in psychiatric care, followed by experiences gathered in conjunction with the application of this approach in this particular sphere, with special reference to three problem areas. These are as follows: the trend towards diagnoses with a relatively high weighting; the practice of charging for psychiatric DRGs in somatic wards; and, finally, the perpetuation of poor service structures and practices through DRGs. In general, evidently the introduction of psychiatric DRGs may also be recommended in Germany because of the danger that otherwise psychiatry might be marginalized and isolated in a corner for chronic medical cases. As the only discipline or specialist sphere with a non-service based budget there is a real threat that funding would be kept low. Thus, under the superior financial conditions in Germany, the disadvantages registered in Hungary would not occur or would become manifest only in a milder form. However, it is important that prior to implementation costing is done with extreme care to determine the relative weighting and duration of treatment for each of the categories and that following introduction of DRGs there is a regular control of coding practices, structure of diagnoses and case-mix changes. PMID- 11199200 TI - [1998 social epidemiological analysis of caries incidence and degree of dental restoration in young men]. AB - Basing on the hypothesis that adult dental health is co-determined by the conditions and influences prevailing in the family of origin during childhood and adolescence, we analysed the associations of socio-economic status of the family, personal dental care behaviour and other educational and structural factors, with caries prevalence (DMF-T) and the level of restoration in 642 young men between 18 and 24 years eligible for conscription. Additionally, we presented the changes in caries prevalence in conscripted persons during the 1990s comparing our results with those of a study conducted in 1989-90. RESULTS: The average number of DMF-T teeth was 5.7. 15% of subjects were caries-free. The mean level of restoration in those with a history of caries was 79.2%. The prevalence of caries and the level of restoration were strongly associated with the level of education, and the socio-economic status of the family of origin. Parental working time, number of siblings, structural deficiencies in the family, parental preventive education and training with regard to dental care, frequency of brushing the teeth, belief in the success of preventive health measures and prevalence of fissure sealings were significantly associated with DMF-T. Frequency of dental visits showed an association with the level of restoration. From 1989/90 to 1998 prevalence of caries in conscripts decreased by 42% (after adjusting for the different levels of education of both studies the decrease was 36%). Whereas in 1989/90 the average number of DMF-T in the 9-year elementary school graduates exceeded those of the high school graduates ("seniors") by 22%, this difference increased to 88% by 1998. More than 40% of the differences in the prevalence of caries among subjects of different educational levels were due to risk factors of social origin, preventive dental behaviour and utilisation of dental services, all of these being less favourable in elementary school or secondary school graduates compared to high-school graduates. PMID- 11199201 TI - [Vaccination status of medical and dental students]. AB - Infectious diseases are still a worldwide health problem, and hence physicians are responsible for providing the population with sufficient vaccinations. Until now, however, comprehensive studies on vaccination behaviour in German medical/dental students, the future physicians/dentists, are lacking. The study analysed vaccinations of medical/dental students against tetanus, diphtheria, poliomyelitis, hepatitis A + B and tried to find possible influences on the vaccination behaviour. 126 medical and 99 dental students participated by working on an anonymous questionnaire related to sociodemographic data, smoking/drinking habits, drug abuse and vaccinations. The response rate was between 76 and 85%. Altogether, the investigated students were not sufficiently vaccinated. Nevertheless, they were better vaccinated than a normal reference sample. Except for a significantly better immunisation against hepatitis B in dental students, no differences between medical and dental students were found. In comparison to male students, female students presented better immunisation. On the other hand, students from the former West Germany, smoking students and students who are taking illegal drugs, were more insufficiently immunised than the other students. To optimise vaccinations in future physicians and dentists, medical/dental education should focus more on infectious diseases and knowledge about vaccinations. This would help to protect future physicians and dentists against preventable infectious diseases. Additionally, they are better skilled to prevent infectious diseases by providing the population with information and vaccinations. PMID- 11199202 TI - [Insufficient ventilation as the etiology of illness perception in an elementary school]. AB - PURPOSE: Two years after renovation of the classrooms in a primary school (installation of insulated windows and closing of the ventilation shaft) pupils and teachers complained about offensive odours, irritation of the eyes and of the nose, complaints of the respiratory tract, headaches and disturbed mental concentration. The presented study determines the causes, suggests measures for help and checks their effectiveness by means of measurements. METHODS: Before starting our measurements, the air quality had already been assessed by an expert. There was no evidence of elevated concentrations of air contaminants. Because of the content of phthalate plasticizers and flame retardants in the linoleum sealants there was an offensive odour. To determine the cause, the air in the subjective mostly affected classroom was analysed for phthalate plasticizers, their metabolites and alkyl phosphates. We also made aerosol measurements with a cascade impactor, determined bacterial counts in the air, and measured the indoor climate and the internal air flow. RESULTS: The concentrations of phthalate plasticizers and their metabolites in the air were not elevated significantly. The screening for alkyl phosphates was negative. The amount of inhalable particles was 0.046 mg/m3. The bacterial count in the air was negligible. On the other hand the indoor climate during the heating period in winter was remarkably changed. The average room temperature was 26 degrees C (reaching a maximum of 36 degrees C with direct sunlight in the classroom), the average humidity was 21% (minimum 7%) and the change of air was approximately 0.5 per hour. Reopening the ventilation shaft and tilting of only one window resulted in a much greater rate of air change. After installation of temperature regulators and regular use of the venetian blinds in the classroom, the room temperature and the relative humidity during the morning lessons were, as a rule, normalised. Among both pupils and teachers the reports of offensive odours and health disorders were subsequently clearly reduced. CONCLUSIONS: To determine the cause of health disorders indoors, it is apparently to be of great importance to carry out measurements of the climate as well as to assess the level of air contaminants. By use of modern energy-saving construction possible effects on the indoor climate should be be taken into account during the planning stage of changes to avoid health disorders resulting from changed interior climate conditions. PMID- 11199203 TI - [Does public access to defibrillators have a chance in Germany?--On the US model, legal considerations and justification]. AB - PURPOSE: The introduction of public access to defibrillation via automated external defibrillators makes it possible to reduce the incidence of sudden cardiac arrest cases. Since they may expect civil and criminal liability after negligence causing damage, many German potential First Responders might hesitate to use an AED. METHODS: After we demonstrate the medical reasons and compare the legal situation of Public Access Defibrillation between the USA and Germany we analyse a possible hesitation of German First Responders. RESULTS: More than 30 states of the USA provide immunity from civil liability after a public access defibrillation followed by damage due to negligence. However, only an AED-trained US-First Responder is granted immunity from civil liability. In Germany there is no immunity from civil and criminal liability in case of public access defibrillation with damage caused by negligence. CONCLUSION: German law will not decrease any possible hesitation by First Responders. For a successful system of public access defibrillation, revision of the legal situation is mandatory. PMID- 11199204 TI - [Public health in homes for the aged and nursing homes--experiences from monitoring by the public health office in Frankfurt am Main from 1989 to 1998]. AB - Hygiene conditions in residential homes for the aged must be surveyed by the Public Health services according to German legislation (Bundesseuchengesetz, Law for Protection against Infectious Diseases). We report here on the data of the routine controls of the public health department in Frankfurt am Main in all of the 31 residential homes for the aged of the city. RESULTS: In 1989, a special plan for cleaning and disinfection was available in one home only, whereas a hygiene plan was not available in any of the homes. Up to 1998, plans for cleaning and disinfection were established in 29 of the homes, and more than 50% of them had fulfilled their hygiene plan. The supply and maintenance of dispersers for disinfectants, the usage of disinfectants and the knowledge regarding proper disinfection and sterilisation procedures could be improved. The same was true of the kitchens: there, up to 1998 testing of samples set aside for later reassessment was properly done in most of the homes. CONCLUSION: Hygiene in the homes and the knowledge of the staff members were markedly improved during the last years. Some of the most relevant hygienic problems are today: wearing private clothing instead of special working clothes, or deficits in the knowledge of the management of MRSA-colonised residents. PMID- 11199205 TI - Synchronization of lactating dairy cows with prostaglandin F2 alpha: insemination on observed oestrus versus timed artificial insemination. AB - The effect of two insemination policies after synchronization of oestrus on reproductive performance in two groups of cows was investigated. Oestrus was synchronized by two treatments with prostaglandin F2 alpha (PGF2 alpha) at a 14 day interval. Cows in Group 1 (n = 234) were inseminated twice on appointment 66 and 90 h after the second treatment. Cows in Group 2 (n = 222) were intensively watched for signs of oestrus after the synchronization protocol and inseminated on observed oestrus. Cows with abnormal discharge after synchronization were excluded from breeding and inseminated later during the study period. Service rate within 1 week after synchronization was higher in Group 1 than in Group 2 (89.3 versus 67.1%). Conception rates on first service did not differ between groups (33.2 versus 30.0%). Days to first service and days open were shorter in Group 1 (P < 0.05). The number of cows culled for infertility did not differ between the groups. Endometritis 14-20 days post-partum decreased the percentage of cows pregnant at the end of the study period in both groups but did not have a significant effect on conception rates and days open. It is concluded that additional inseminations required in the timed artificial insemination protocol were economically justified by the reduction in days open in comparison with insemination on observed oestrus after synchronization. PMID- 11199206 TI - Binding profile of spiramycin to oviducal proteins of laying hens. AB - In vitro protein binding of spiramycin (SP) in the plasma and oviducts of laying hens was studied. The data for SP were compared with those for oxytetracycline (OTC), sulphadimidine (SDD), sulphamonomethoxine (SMM) and sulphaquinoxaline (SQ). The two oviduct segments, magnum (M) and isthmus plus shell gland (IS), were collected. The soluble (cell sap) fractions from the magnum (M-S9) and the isthmus plus shell gland (IS-S9) were used as samples. Plasma protein binding was highest for SQ (81.4%) (P < 0.01), and lowest for SDD (30.9%) (P < 0.01). No M-S9 protein binding of OTC was found. The IS-S9 protein binding of SP (60.4%) was very much higher than those of OTC (0.8%), SDD (4.1%), SMM (4.0%) and SQ (12.3%) (P < 0.01). Biological half-lives of these drugs in egg albumen were directly correlated to the extent of their binding to IS proteins. Of plasma, M-S9 and IS S9, variation in SP concentration in the ranges from 1 to 20 micrograms/ml did not alter the binding properties of the drug. PMID- 11199207 TI - Comparative studies in the promoter and exon 1 regions of tumour suppressor p53 in several mammalian species: absence of mutations in a panel of spontaneous domestic animal tumours. AB - Tumour suppressor p53 is critical in a broad panel of tumour types in human, mouse and other mammals. Regions of the promoter and exon 1 play an important role in expression of p53. In the present study, the DNA sequences of promoter and exon 1 regions of four domestic animal species (dog, cat, horse and cattle) are determined and compared with experimental rodents (mouse, rat and hamster) and man. A broad panel of tumour types have been investigated for mutations in this regulatory area in 90 canine, 136 feline, 25 equine and 10 bovine patients. No mutation was detected in any of the tumours analysed. PMID- 11199208 TI - Effects of vitamin E and different energy sources on vitamin E status, milk quality and reproduction in transition cows. AB - We investigated whether vitamin E supplementation and supplemental energy sources (fat or starch) influenced plasma and milk levels of vitamin E, and reproductive and other parameters in 28 Italian Friesian multiparous dry cows. From 14 days before expected calving to 7 days after, the animals were assigned to either basal diet (containing 1000 IU/day of vitamin E) or an extra 1000 IU/day of vitamin E (total 2000 IU). In addition they received either 0.5 kg/day of corn or 0.2 kg/day of calcium soaps. Plasma samples were collected 4 days before expected calving and 4 days after calving and analysed for alpha-tocopherol and cholesterol. Milk yield as well as the composition, somatic cell count (SCC) and alpha-tocopherol of milk were determined 7 and 14 days after calving. Milk yield and composition were unaffected by treatments. SCC was significantly lower in (SCC Log 4.62 versus Log 5.1, P < 0.01) 2000 IU/day animals than in the 1000 IU/day group. Milk alpha-tocopherol was higher (P < 0.001) in animals receiving 2000 IU/day (1.11 vs. 0.65 microgram/ml, P < 0.01). Plasma alpha-tocopherol in animals receiving 2000 IU/day was also higher (P < 0.001) than in cows receiving 1000 IU/day (4.85 vs. 3.25 micrograms/ml), but was not affected by dietary energy source. Number of services and days to conception were lower (P < 0.01) in the 2000 IU vitamin E supplemented cows. To conclude, dietary vitamin E supplementation to periparturient dairy cows increased plasma and milk vitamin E, decreased SCC in milk, and improved fertility but different energy sources had no effect on any measured variable. PMID- 11199209 TI - Reproductive efficiency of cows with endometritis after treatment with intrauterine infusions or prostaglandin injections, or no treatment. AB - Data from 3276 cows with 6598 lactations in 85 herds participating in a herd health monitoring programme were selected for an observational study. Cases of endometritis were diagnosed based on a clinical examination after 21 days postpartum. The cases were grouped by the severity of endometritis (mild, severe) and by the treatment performed (intrauterine infusion, prostaglandin injection, no treatment). The conception rates and the calving-to-conception intervals of these groups were compared statistically. Conception rate was lower in cows with severe endometritis compared to cows with mild endometritis while it did not differ between treatment groups. In cows with mild endometritis a significantly longer calving-to-conception interval was observed if intrauterine infusions were performed compared to the other two treatment options. The occurrence of other fertility problems during the same service period had a significant effect on conception rate and calving-to-conception intervals. In cows with severe endometritis intrauterine or prostaglandin treatments appeared to be beneficial, whereas intrauterine infusions in cows with slight endometritis had a negative effect on reproductive efficiency. PMID- 11199210 TI - Na(+)-dependent transport of D-xylose by bovine intestinal brush border membrane vesicles (BBMV) is inhibited by various pentoses and hexoses. AB - To detect whether pentoses and hexoses occurring in rumen bacteria or in hemicellulose ingested with feed and partly released in the small intestine have an affinity for the Na(+)-dependent glucose transporter of the bovine intestinal brush border membrane (BBM), we investigated whether these monosaccharides inhibit Na(+)-dependent transport of 14C-labelled D-xylose across the BBM using brush border membrane vesicles (BBMV) isolated from the mid-jejunum of cows. We used D-xylose as the transport substrate, because it has a low affinity for the Na(+)-dependent glucose transporter and thus its uptake into BBMV is more efficiently competitively inhibited by other sugars than that of D-glucose. D Ribose, D-mannose and L-rhamnose occurring in rumen bacteria significantly inhibited Na(+)-dependent uptake of D-xylose into BBMV, but their inhibitory effect was less than that of D-glucose, D-xylose and phlorizin. This also applied to L-arabinose (and D-arabinose), which is, like D-xylose and D-galactose, a constituent of hemicellulose, and to 2-deoxy-D-glucose. Of all monosaccharides tested, only D-fructose did not affect Na(+)-dependent D-xylose transport. It is concluded that some pentoses and hexoses occurring in rumen bacteria (D-ribose, D mannose and L-rhamnose) or hemicellulose (L-arabinose and D-xylose) have a low affinity for the Na(+)-dependent glucose transporter of the bovine BBM and may therefore be absorbed from the jejunum when released in the small intestine. PMID- 11199211 TI - The effect of repeated follicular puncture on ovarian function in dairy heifers. AB - Three dairy heifers were examined during three consecutive oestrous cycles (control period, CP). Subsequently, the animals were subjected to 4 and then 5 weeks of twice-weekly ovum pick-up (OPU) (FPP1 and FPP2, respectively) with a recovery period (RP) of two consecutive oestrous cycles between FPP1 and FPP2. After FPP2, the animals were slaughtered and the ovaries were macroscopically examined. Throughout, ovarian activity was monitored by transrectal ultrasonography and concentrations of plasma progesterone. During CP, all the heifers showed normal cyclicity. During FPPs, the heifers occasionally presented oestrous activity. Corpus luteum (CL)-like structures developed from punctured follicles with diameters and life-spans varying from smaller and shorter than those in the CP (P > 0.05) to equal to those in the CP. There was a tendency for a lower number of emerging and punctured follicles in the presence of a CL-like structure. Subsequently to FPP1, all heifers regained normal cyclicity. A thickening of the ovarian tunica albuginea and a slight hardening of the ovaries were found postmortem. In conclusion, dairy heifers can occasionally show cyclic activity and form CL-like structures during twice-weekly OPU. Further, OPU did not seem to cause any major negative effects on ovarian structure and subsequent ovarian function. PMID- 11199212 TI - A stability-indicating LC method for the simultaneous determination of ramipril and hydrochlorothiazide in dosage forms. AB - A simple, rapid and sensitive HPLC method has been developed for the simultaneous determination of ramipril and hydrochlorothiazide in their dosage forms. Acetonitrile: sodium perchlorate solution (0.1 M) adjusted to pH 2.5+/-0.2 with phosphoric acid (46:54 v/v), was used as the mobile phase, at a flow rate of 1.5 ml/min. A supelcosil LC-8 column (5 microm), 15 cm x 4.6 mm i.d. was utilized as stationary phase. Detection was affected spectrophotometrically at 210 nm. Clobazam was used as an internal standard. The method was also applied for the determination of ramipril in the presence of its degradation products. Linearity ranges for ramipril and hydrochlorothiazide were 4.5-45 and 0.6-14 microg/ml, respectively. Minimum detection limits (S/N = 2) obtained were 180 and 23 ng/ml for ramipril and hydrochlorothiazide, respectively. The proposed method was further applied to the analysis of tablets containing the two drugs, the percentage recoveries +/- S.D. (n = 5) were 100.45%+/-0.63 and 99.55%+/-0.78 for ramipril and hydrochlorothiazide, respectively. PMID- 11199213 TI - Visualization of fluid-bed granulation with self-organizing maps. AB - The degree of the instrumentation of pharmaceutical unit operations has increased. This instrumentation provides information of the state of the process and can be used for both process control and research. However, on-line process data is usually multidimensional, and is difficult to study with traditional trends and scatter plots. The Self-Organizing Map (SOM) is a recognized tool for dimension reduction and process state monitoring. The basics of the SOM and the application to on-line data collected from a fluid-bed granulation process are presented. As a batch process, granulation traversed through a number of process states, which was visualized with SOM as a two-dimensional map. In addition, it is demonstrated how the differences between granulation batches can be studied. The results suggest that SOM together with new in-line process analytical solutions support the in-process control of the pharmaceutical unit operations. Further, a novel research tool for understanding the phenomena during processing is achieved. PMID- 11199214 TI - Optimization of TLC analysis of flavonoids and phenolic acids of Helleborus atrorubens Waldst. et Kit. AB - Numerical methods for the evaluation of the separation power of thirteen thin layer chromatographic systems for splitting a methanolic extract of leaves of Helleborus atrorubens Waldst. et Kit. into 15 compounds (flavonoids and phenolic acids) have been investigated. For this purpose, the following mathematical approaches have been applied: calculation of the information content (I), determination of discriminating power (DP) and formation of clusters and dendrogram. The most suitable chromatographic system for the separation of investigated compounds is ethyl acetate-formic acid-water (65:15:20, v/v/v). PMID- 11199215 TI - Ion-selective piezoelectric sensor for niacinamide assay in serum and urine. AB - An ion-selective piezoelectric (ISP) sensor was successfully applied for the determination of niacinamide in serum and urine. By coating a polyvinylchloride membrane containing niacinamide-silicotungstate on one electrode of a thickness shear mode piezoelectric quartz crystal, the ISP device can adsorb niacinamide selectively. The amount of coating applied to the crystal was calculated from the Sauerbrey equation by monitoring the frequency change. The logarithm of the frequency shift was linear with the logarithm of niacinamide concentration over the range from 1.0 x 10(-9) to 1.0 x 10(-3) M with a detection limit of 1.0 x 10( 9) M at pH 7.0. Influencing factors were investigated and optimized. The results for real samples obtained by the proposed method were in good agreement with those obtained by the conventional methods. PMID- 11199216 TI - A stability-indicating HPLC assay method for budesonide. AB - The official (European) pharmacopeial assay for budesonide was found to be non specific and non-stability-indicating when used to qualify several batches of pharmaceutical grade drug substance from different sources. In contrast, the most widely cited HPLC method in the literature was found to be specific and stability indicating with respect to drug substance stored in the dry state. However, that method failed the pharmacopeia's assay system suitability requirements because of peak tailing. Moreover, it was unable to detect or resolve two major degradation products which resulted from drug storage in non-aqueous solution. A new stability-indicating HPLC method described here overcomes these problems. This method used a Hypersil C18 column with a mobile phase consisting of ethanol acetonitrile phosphate buffer (pH 3.4; 25.6 mM) (2:30:68, v/v/v), a flow rate of 1.5 ml/min and UV detection at 240 nm. The purity of budesonide EP and its impurity profile (related substances) were tested using the new assay method, and the results compared to those from the two other methods described above. Solid state and solution stressed stability samples were used to evaluate all methods. Using the novel method, the epimers of budesonide. their related impurities and degradation products were separated successfully. Validation studies demonstrated that the novel method possessed a linear UV response, good system precision and accuracy, high sensitivity and specificity for budesonide. The novel method will be used for future studies of budesonide's degradation kinetics. PMID- 11199217 TI - Determination of cilostazol and its metabolites in human urine by high performance liquid chromatography. AB - A high performance liquid chromatography (HPLC) method with ultraviolet detection for the simultaneous quantification of cilostazol, and its known metabolites in human urine was developed and validated. Cilostazol, its metabolites and the internal standard OPC-3930 (structural analogue of cilostazol) were extracted from human urine using liquid-liquid extraction with chloroform. The organic extract was then evaporated and the residue was reconstituted in 8% acetonitrile in ammonium acetate buffer (pH 6.5). The reconstituted solution was injected onto an HPLC system and was subjected to reverse-phase HPLC on a 5-microm ODS column. A gradient mobile phase with different percentages of acetonitrile in acetate buffer (pH 6.5) was used for the resolution of analytes. Cilostazol, its metabolites and the internal standard were well resolved at baseline with adequate resolution from constituents of human urine. The lower limit of quantification was 100 ng/ml for cilostazol and all metabolites. The method was validated for a linear range of 100-3000 ng/ml for all the metabolites and cilostazol. The overall accuracy (% relative recovery) of this method ranged from 86.1 to 116.8% for all the analytes with overall precision (%CV) being 0.8-19.7%. The long-term stability of clinical urine samples was established for at least 3 months at -20 degrees C in a storage freezer. During validation, calibration curves had correlation coefficients greater than or equal to 0.995 for cilostazol and the seven tested metabolites. The method was successfully used for the analysis of cilostazol and its metabolites in urine samples from clinical studies, demonstrating the reliability and robustness of the method. PMID- 11199219 TI - Determination of isepamicin sulfate and related compounds by high performance liquid chromatography using evaporative light scattering detection. AB - A simple reversed phase high performance liquid chromatographic method was developed for the analysis of isepamicin sulfate. The use of evaporative light scattering detection eliminates the need for sample derivatization. Separation of the isepamicin aminoglycoside from structurally similar related compounds was achieved using two Waters X-Terra RP18 columns connected in tandem at 10 degrees C. The assay of isepamicin sulfate and the estimation of its impurities was accomplished using external standard calibration curves at two sample concentrations: 1.6 mg ml(-1) for the analysis of isepamicin sulfate and 8.0 mg ml(-1) for the estimation of lower level impurities. The limit of detection was 0.1%. The specificity, assay linearity, low level assay linearity and assay repeatability were also investigated. PMID- 11199218 TI - Validation of an HPLC method for the determination of urinary and plasma levels of N1-methylnicotinamide, an endogenous marker of renal cationic transport and plasma flow. AB - N1-Methylnicotinamide (NMN) is an endogenous cationic metabolite of nicotinamide (niacine, vitamine PP) whose renal clearance reflects both the capacity of the renal tubular transport system to secrete organic cations and renal plasma flow. NMN is present in human plasma and urine at the 1-117-ng ml(-1) and 0.5-25-microg ml(-1) concentration range, respectively, and its level depends notably on pathophysiological (age, renal or hepatic diseases) conditions. We report the optimization and validation of an HPLC method for the measurement of endogenous NMN in biological fluids after derivatization into a fluorescent compound. Plasma is first deproteinized with TCA 20% and the urine diluted 1:10 with HCI 10(-4) M prior to the derivatization procedure, which includes a condensation reaction of NMN with acetophenone in NaOH at 0 degrees C, followed by dehydration in formic acid and subsequent formation of the fluorescent 1,6-naphthyridine derivatives after heating samples in a boiling water bath. The synthetic homologous derivative N1-ethylnicotinamide (NEN) reacts similarly and is added as internal standard into the biological fluid. The reaction mixture is subjected to reverse phase high performance liquid chromatography on a Nucleosil 100-C18 column using a mobile phase (acetonitrile 22%, triethylamine 0.5%, 0.01 M sodium heptanesulfonate adjusted to pH 3.2), delivered isocratically at a flow rate of 1 ml min(-1), NMN and NEN are detected at 7.8 and 10 min by spectrofluorimetry with excitation and emission wavelengths set at 366 and 418 nm, respectively. The addition-calibration method is used with plasma and urine pools. Calibration curves (using the internal standard method) are linear (r2 > 0.997) at concentrations up to 109 ng ml(-1) and 15.7 microg ml(-1) in plasma and urine, respectively. Both intra- and inter-assay precision of plasma control samples at 10, 50 and 90 ng ml(-1) were lower than 3.3% and concentrations not deviating more than 2.7% from their nominal values. In urine intra- and inter-assay CVs of control samples at 1, 5 and 9 microg ml(-1) are lower than 8.3%, with concentrations not deviating more than -9.0 to +11.8% from their nominal values. This analytical method has therefore the required sensitivity and selectivity to measure NMN in plasma and urine, enabling the non-invasive determination of the tubular secretory capacity of the kidney and the renal plasma flow. PMID- 11199220 TI - Stripping voltammetric determination of indapamide in serum at castor oil-based carbon paste electrodes. AB - The diuretic drug indapamide has been characterized voltammetrically at carbon paste electrodes by means of cyclic and differential pulse voltammetry. An adsorptive stripping method at carbon paste electrode modified with castor oil for trace determination of indapamide was described. A study of the variation of the peak current with solution variables such as pH, ionic strength, concentration of indapamide, possible interference, and instrumental variables such as scan rate, pulse amplitude, preconcentration time, accumulation potential, paste composition has resulted in the optimization of the oxidation signal for analytical purposes. By anodic stripping differential pulse voltammetry, the calibration plot was linear in the range 5 x 10(-8) x 10(-7) M with a detection limit of 5 x 10(-9) M at carbon paste electrode modified with castor oil in pH 4.0. The preconcentration medium-exchange approach was utilized for selective determination of indapamide in spiked serum. A detection limit of 15 ng ml(-1) was obtained for dilute serum sample after 3 min accumulation and medium-exchange procedure. PMID- 11199221 TI - Determination of ambroxol or bromhexine in pharmaceuticals by capillary isotachophoresis. AB - Expectorant drugs ambroxol (AX) and bromhexine (BX) were determined by capillary isotachophoresis (ITP) with conductimetric detection. The leading electrolyte (LE) was a buffer solution that contained 5 mM picolinic acid and 5 mM potassium picolinate (pH 5.2). The terminating electrolyte (TE) was 10 mM formic acid. The driving current was 80 microA (for approximately 200 s) or 50 microA (for approximately 350 s) and the detection current was 20 microA (a single analysis took about 8 min). The effective mobilities of AX and BX (evaluated with tetraethylammonium as the mobility standard) were 18.8 x 10(-9) m2 V(-1) s(-1) and 14.3 x 10(-9) m2 V(-1) s(-1) respectively. The calibration graphs relating the ITP zone length to the concentration of the analytes were rectilinear (r = 0.9993-0.9999) in the range 10 mg L(-1) (20 mg L(-1) for BX) to 200 mg l(-1) of the drug standard. The relative standard deviations (RSD) were 1.2 1.6% (n = 6) when determining 100 mg l(-1) of the analytes in pure test solutions. The method has been applied to the assay of AX or BX in seven commercial mass-produced pharmaceutical preparations. According to the validation procedure based on the standard addition technique the recoveries were 97.5-102.7% of the drug and the RSD values were 0.11-2.20% (n = 6). PMID- 11199222 TI - Immunoreactivity of 80-kDa peptidoglycan and teichoic acid-like substance of slime producing S. epidermidis and specificity of their antibodies studied by an enzyme immunoassay. AB - S. epidermidis is considered an important cause of nosocomial bacteraernia in immunocompromized hosts as well as the commonest agent of sepsis in patients with prosthetic devices. Pathogenesis is attributed to adherence and growth on bioniaterials facilitated by production of extracellular slime. The major macromolecules of slime are: a 20-kDa acidic polysaccharide (20-kDa PS) comprising the 60% of carbohydrate-containing slime macromolecules, a peptidoglycan with average molecular size of 80-kDa (30% of slime dry weight) and cell wall teichoic acid-like substance. In this study, antibodies to these macromolecules as well as crude slime were raised in rabbits and their immunological reactivity and specificity were studied by an enzyme immunoassay. All isolated macromolecules induced the production of specific antibodies. 20-kDa PS was less immunogenic than 80-kDa peptidoglycan and teichoic acid-like substance. However, 20-kDa PS was the most potent inhibitor of the reaction of slime with its homologous antibodies revealing that this polysaccharide is the major antigenic determinant of slime. All three antibodies specifically recognize (p < 0.05) and react with slime-producing S. epidermidis in comparison to other staphylococci species. Obtained results indicate that the 20-kDa PS may be distributed in the surface of the slime exposing most of its antigenic determinants to the immune system, whereas those of 80-kDa peptidoglycan and teichoic acid-like substance seem to be less accessible. PMID- 11199223 TI - A method for measuring potency of narasin extracts using near-IR spectroscopy. AB - We present a method for extracting the active component from granulated narasin samples using chloroform with subsequent quantitation by near-infrared absorption spectroscopy (NIRS). A multiple linear regression (MLR) calibration equation was developed using a set of 41 calibration samples. The potencies obtained using NIR analysis exhibit no larger than an 8% (3.03 mg/g) error when compared to results based on the primary HPLC reference method. We estimate the detection limit using this method to be 400 ppm narasin (20 mg/g potency), and the standard deviation for five independent extractions of the same sample is approximately 24 ppm (approximately 1.2 mg/g potency or approximately 1%). We also present the results from a robustness study based upon a full factorial experimental design in which we varied extraction and measurement parameters. This study indicates that sample mass causes the most variation in the results. Bottle-to-bottle variations in the chloroform used for the extraction also proved significant. Variations in sample batch, number of spectral scans, and the interactions between sample hatch*soneration time, no. Scans*time in NIR, and sample batch*sample mass were borderline significant. PMID- 11199224 TI - A single-channel method for evaluation of very magnitudes of Ca2+ ion fluxes through epsilon4/zeta1 N-methyl-D-aspartate receptor channels in bilayer lipid membranes. AB - A single-channel method for evaluating agonist selectivity in terms of the very number of Ca2+ ions passed through the epsilon4/zeta1 N-methyl-D-aspartate (NMDA) receptor ion channel in bilayer lipid membranes (BLMs) is described. The number of Ca2+ passed through the single-channel was obtained from single-channel recordings in a medium where the primary permeant ion is Ca2+. The recombinant epsilon4/zeta1 NMDA channel was partially purified from Chinese hamster ovary cells expressing the channel and incorporated in BLMs formed by the tip-dip method. It was found that the epsilon4/zeta1 channel in BLMs is permeable to Ca2+ and Na+, but the number of Ca2+ passed through the channel is much fewer than that of Na+. The integrated Ca2+ currents induced by three typical agonists NMDA, L-glutamate and L-CCG-IV were obtained at concentration of 50 microM, where the integrated currents for all the agonists reached their saturated values. The integrated Ca2+ currents obtained are (3.1+/-0.21) x 10(-13) C/s for NMDA, (4.6+/ 0.31) x 10(-13) C/s for L-glutamate and (5.7+/-0.25) x 10(-13) C/s for L-CCG-IV, respectively, suggesting that the three kinds of agonists have different efficacies to induce permeation of Ca2+. The range of the agonist selectivity thus obtained is much narrower than that of binding affinities for the NMDA receptors from rat brain. The present method is able to detect Ca2+ permeation with a detection limit of approximately 10(5) Ca2+ ions/s. PMID- 11199225 TI - High-performance liquid chromatographic analysis and stability of anti-tumor agent temozolomide in human plasma. AB - Temozolomide (SCH 52365; TEMODAL) is an antineoplastic agent with activity against a broad spectrum of murine tumors. This compound is currently marketed in the European Union for the treatment of patients with glioblastoma multiforme and anaplastic astrocytoma, which are serious and aggressive types of brain cancers. It has been postulated that temozolomide exerts its in vivo activity via the decomposition product MTIC, which is believed to alkylate nucleophiles, and in the process is converted to AIC. A high-performance liquid chromatographic (HPLC) method was developed and validated for the analysis of temozolomide in human plasma. The determination of temozolomide involved extraction with ethyl acetate followed by separation on a reversed phase C-18 column and quantification by UV absorbance at 316 nm. The calibration curve was linear over a concentration range of 0.1-20 microg/ml. The limit of quantitation was 0.1 microg/ml, where the coefficient of variation (CV) was 0% and the bias was 10.0%. The method was precise with a coefficient of variation ranging from 2.5 to 6.9% and accurate with a bias ranging from 5.0 to 10.0%. Temozolomide was unstable at 37 degrees C in human plasma with a degradation t1/2 of 15 min; however, it was stable at 4 degrees C for at least 30 min. Temozolomide was stable in acidified human plasma (pH < 4) for at least 24 h at 25 degrees C, and for at least 30 days at -20 degrees C. Moreover, temozolomide was stable in acidified human plasma after being subjected to three freeze thaw cycles. The assay was shown to be specific, accurate, precise, and reliable for use in pharmacokinetic studies. PMID- 11199226 TI - Simultaneous determination of paracetamol and methocarbamol in tablets by ratio spectra derivative spectrophotometry and LC. AB - The application of the ratio spectra derivative spectrophotometry and high performance liquid chromatography (HPLC) to the simultaneous determination of paracetamol (PAR) and methocarbamol (MET) in combined pharmaceutical tablets is presented. The spectrophotometric procedure is based on the use of the first derivative of the ratio spectra obtained by dividing the absorbtion spectrum of the binary mixtures by a standard spectrum of one of the compounds. The first derivative amplitudes were measured at 243.0 and 230.3 nm for the assay of PAR and MET, respectively. Calibration graphs were established for 2-30 microg ml for PAR and 2-36 microg/ml for MET in binary mixture. The detection limits for PAR and MET were found 0.097 and 0.079 microg/ml, respectively; while the quantification limits were 0.573 microg/ml for PAR and 1.717 microg/ml for MET. For the HPLC procedure, a reversed-phase column with a mobile phase of methanol water (60:40, v/v), was used to separate both compounds with a detection of 274.0 nm. Linearity was obtained in the concentration range of 2 300 and 1.5-375 microg/ml for PAR and MET, respectively. The detection and quantification limits were found to be 0.42 and 1.4 microg/ml for PAR and 0.36 and 1.2 microg/ml for MET, respectively. The relative standard deviations were found to be less than 0.52%, indicating reasonable repeatibility of both methods. The proposed methods were successfully applied to the determination of these drugs in commercial tablets. PMID- 11199227 TI - LC-1H NMR used for determination of the elution order of S-naproxen glucuronide isomers in two isocratic reversed-phase LC-systems. AB - The reactive metabolite S-naproxen-beta-1-O-acyl glucuronide was purified from human urine using solid phase extraction (SPE) and preparative HPLC. The structure was confirmed by 600 MHz 1H NMR. Directly coupled 600 MHz HPLC-1H NMR was used to assign the peaks in chromatograms obtained when analysing a sample containing S-naproxen aglycone and the 1-, 2-, 3-, and 4-isomers of S-naproxen beta-1-O-acyl glucuronide in two simple isocratic reversed phase HPLC-systems. Using mobile phase 1 (50 mM formate buffer pH 5.75/acetonitrile 75:25 v/v) the elution order was: 4-O-acyl isomers, beta-1-O-acyl glucuronide, 3-O-acyl isomers, 2-O-acyl isomers, and S-naproxen aglycone. Using mobile phase II (25 mM potassium phosphate pH 7.40/acetonitrile 80:20 v/v) the elution order was: alpha/beta-4-O acyl isomers, S-naproxen aglycone, beta-1-O-acyl glucuronide, 3-O-acyl isomers, and alpha/beta-2-O-acyl isomers. In both systems the elution order for the 2-, 3- and 4-O-acyl isomers corresponded with previously published results for 2-, 3-, and 4-fluorobenzoic acid glucuronide isomers determined by reversed phase HPLC-1H NMR (U.G. Sidelmann, S.H. Hansen, C. Gavaghan, A.W. Nicholls, H.A.J. Carless, J.C. Lindon, I.D. Wilson, J.K. Nicholson, J. Chromatogr. B Biomed. Appl. 685 (1996) 113-122]. The alpha-1-O-acyl isomer was found to be present at approximately 3% of the initial S-naproxen-beta-1-O-acyl glucuronide concentration in the glucuronide isomer mixture after 6 h of incubation at pH 7.40 and 37 degrees C. In both HPLC systems it eluted just before the beta-1-O acyl glucuronide well separated from other isomers. Investigators should consider the possible formation of a alpha-1-O-acyl isomer when studying glucuronide reactivity and degradation. PMID- 11199228 TI - Determination of perfluorobutane in rat blood by automatic headspace capillary gas chromatography and selected ion monitoring mass spectrometry. AB - A new contrast agent (Sonazoid; NC100100) for ultrasound imaging has been developed. It is an aqueous suspension of lipid stabilised perfluorobutane (PFB) gas microbubbles. An automatic headspace capillary gas-chromatographic mass spectrometric method using electron impact ionisation was developed for analysis of Sonazoid PFB in rat blood. The calibration standards were gaseous PFB dissolved in ethanol in the range of 0.5-5000 ng PFB. Fluorotrichloromethane (CFC 11) was used as an internal standard of the method and the MS detector was set to single ion monitoring of the base fragment ions of PFB (m/z 69 and 119) and CFC 11 (m/z 101). The calibration graph, made by plotting the peak area ratios of PFB (m/z 69) to CFC 11(m/z 101) against the amount of PFB, was fitted to a second order polynomial equation with weighting 1/y2 and found to be reproducible. The limit of quantification of the method was set to 0.4 ng PFB. The between-day variation of the method was below 9.2% relative standard deviation (RSD) and the within-day variation of the method was below 7.6% RSD. The accuracy of the method, as compared to Coulter counter, was estimated by determination of PFB in samples where Sonazoid was added to saline and found to range from 91.5% to 105.2%. PFB, added as Sonazoid, was found to be stable for at least 7 months in rat blood samples when stored at -20 degrees C. PMID- 11199229 TI - Determination of Cremophor EL in plasma after sample preparation with solid phase extraction and plasma protein precipitation. AB - The non-ionic emulsifier Cremophor EL can be quantified using a special potentiometric titration technique with barium chloride activation and precipitation with sodium tetraphenylborate. The end point of the titration is indicated by an ionsensitive coated wire electrode which responds to an excess of tetraphenylborate ions. Sample preparation is necessary to quantify the excipient in plasma of patients receiving ciclosporin formulations with Cremophor EL (Sandimmun), since plasma proteins cause disturbances of the titration. Solid phase extraction was tested with various sorbent materials. Although some of the sorbents yielded good extraction rates of Cremophor EL from aqueous solutions, the extraction rates from plasma were significantly lower. Therefore, plasma protein precipitation with acetonitrile has been examined as an alternative to SPE and has been proved the superior method. Using the precipitation technique, a recovery rate of above 90% was achieved. Furthermore, the limit of detection from plasma was found to be 30 microg, in analogy to the determination from aqueous solutions. The combination of the plasma protein precipitation with the potentiometric titration allows quantitation and thus pharmakokinetic investigations of Cremophor EL in patients treated with Sandimmun after kidney transplantation. PMID- 11199230 TI - Analysis of glimepiride by using derivative UV spectrophotometric method. AB - Glimepiride (Amaryl), which is a new oral antidiabetic drug in the sulfonylurea class, was analysed by using second order derivative UV spectrophotometry. The quantification of glimepiride in dimethylformamide was performed in the wavelength range of 245-290 nm at N = 6, ?lambda = 21. The second order derivative spectra was calculated using peak to peak (lambdaDMF = 263.3-268.2 nm), peak to zero (lambdaDMF = 268.2 nm) and tangent (lambdaDMF = 263.3-271.8 nm) method for calibration curves, the linearity range of 1.00-500.00 microg ml(-1) by using the second order derivative UV spectrophotometric method. The developed method was applied to directly and easily to the analysis of the pharmaceutical tablet preparations. R.S.D. were found to be 4.18% (Amaryl tablet; 1 mg) and 2.21% (Amaryl tablet; 2 mg). The method was completely validated and proven to be rugged. The limit of quantitation and the limit of detection were found as 1.00 and 0.4 microg ml(-1), respectively. This validated derivative UV spectrophotometric method is potentially useful for a routine laboratory because of its simplicity, rapidity, sensitivity, precision and accuracy. PMID- 11199231 TI - LC coupled to ion-trap MS for the rapid screening and detection of polyphenol antioxidants from Helichrysum stoechas. AB - Liquid Chromatography-Ion Trap Mass Spectrometry with an atmospheric pressure chemical ionization (APCI) interface in the negative and positive-ion modes in parallel to UV-diode-array detection (DAD), was applied for the rapid detection/characterization in crude extracts of the water-soluble antioxidant phenolics from Helichrysum stoechas. APCI-MS provides unequivocal molecular weight data of these compounds and useful information about their structures (diagnostic fragments ions), which were confirmed by the UV-DAD fingerprints. This combined approach allows the identification of ten constituents, including the three naturally occurring isomers of caffeoylquinic acid (CGAs), namely neo chlorogenic acid, chlorogenic acid and crypto-chlorogenic acid, 2 isomeric dicaffeoyl quinic acids, 2 isomeric naringenin glucosides, quercetin, kaempferol and apigenin glucosides and a tetrahydroxychalcone-glucoside. The water-soluble extract from H. stoechas, standardized in both total polyphenol and kaempferol-3 glucoside content, exhibits strong antioxidant activity in vitro when tested in both artificial membrane systems (phosphatidylcholine liposomes) and in a cell model (rat erythrocytes). PMID- 11199232 TI - Milly Haagedoorn awarded the 2000 Margaret Hay Edwards Achievement Medal. PMID- 11199233 TI - The Cancer Education Grant Program of the National Cancer Institute. PMID- 11199234 TI - Cancer skills laboratories for medical students: a promising approach for cancer education. AB - BACKGROUND: Most medical students graduate without the skills necessary to assist patients in cancer control. To address this problem, the authors developed a cancer skills laboratory for second-year medical students. METHODS: The skills laboratory consists of two hours of training, with 15 minutes allotted per station (six to eight students assigned per station). Faculty and fellows lead the stations on prostate cancer, breast cancer, colorectal cancer, skin cancer, counseling for smoking cessation, and a discussion of anti-tobacco advertisements. Students completed pre- and post-laboratory surveys consisting of ten brief questions. RESULTS: Overall, 94% of eligible students in 1997 and 1998 completed the surveys. Using a five-point scale, self-rated skill level increased from 2.12 to 3.83 when all modalities were averaged (p < .001). CONCLUSIONS: Cancer skills laboratories are a promising new means for cancer education. PMID- 11199235 TI - Effective use of the web to expand a summer predoctoral program: the St. Jude experience. AB - BACKGROUND: Since 1978, the St. Jude Children's Research Hospital has oncology education (POE) program for medical and other health professional students to do two-to-four-month clinical and/or basic research rotations in pediatric oncology. Limitations in funding, recruitment capability, and faculty interest held student numbers to 0-18 per year. METHODS: In early 1997, the program announcement and an on-line application were put on the Web site, . An applicant's online submission is delivered immediately to the program director's e-mail inbox, promptly acknowledged via e-mail, transferred to a digital database, and forwarded electronically to prospective institutional preceptors. RESULTS: The program accepted 36 of 61 applicants (56% minority) in 1997. A supplemental funding award enabled expansion of the program to include students preparing for health professions or biomedical sciences careers. In 1999, 75 of 139 applicants were accepted (47% minority) from 39 schools in 18 states, the District of Columbia, Puerto Rico, Mexico, and Ireland. CONCLUSIONS: Effective use of the Web and e-mail made it possible to inform students effectively about the institution and program, match students with preceptors, increase the number of minority participants, and expand the regional program into a national one. PMID- 11199236 TI - The UICC/WHO-CCCE Cancer Education project: a different approach. AB - The Union Internationale Contre le Cancer (UICC) and the WHO-Collaborating Centre for Cancer Education (WHO-CCCE) have started an international pilot project offering assistance to medical schools that want to implement in their curricula a two-week multidisciplinary cancer course aimed at cancer care in general practice. The approach will be bottom-up (based on the possibilities in individual medical schools) instead of top-down (based on general recommendations and rules established in published studies). In April 2000 one or more medical schools from each of four continents had registered. Registration is open to any medical school and to other schools that have satisfactory ongoing cancer courses. The aim is to develop a network among medical schools in order for them to learn from each other's cancer education strategies and experiences. PMID- 11199237 TI - Assessing the need for Clinical Breast Examination (CBE) training: the Oregon experience. AB - BACKGROUND: Despite the widely held perception that CBE training has high priority among the continuing medical education (CME) needs of breast health care providers, there is actually little published information to support this notion. METHODS: The authors conducted a statewide needs assessment mail survey of providers regarding a number of potential CME needs, including CBE training. RESULTS: Of the 4,179 surveys from the single mailing, 1,427 were returned (34% response rate). Six categories of provider types responded; 51% were physicians and 23% were nurse practitioners. Fifty-nine percent of the respondents were female; 96% felt that routine CBE was an important or very important part of providing breast care. Although 79% of all respondents performed CBE at least weekly and 41% performed more than ten CBEs/week, 80% were interested in receiving some form of CME regarding CBE, and 79% of those who performed CBE at least weekly were interested in receiving skill-based CBE training. CONCLUSIONS: Despite the respondent bias inherent in survey studies, it can be concluded that there is indeed a CME need for CBE training, even among providers who perform CBE frequently. Based on these findings the authors are implementing a statewide CME program of CBE training. PMID- 11199238 TI - The effects of a postgraduate course on opioid-prescribing patterns of general practitioners. AB - BACKGROUND: The objective of this study is to evaluate whether a single palliative cancer care workshop, which included information about drug prescribing, had an effect on the opioid-prescription patterns of general practitioners in daily practice. METHOD: The opioid-prescription figures of 68 general practitioners who had participated in the workshop were aggregated from the computer system of the Regional Sick Fund. The prescription figures of a year before and a year after the workshop were compared and a control group of non participants was included. RESULTS: This study showed a limited efficacy of a palliative cancer care workshop on the morphine-prescription figures of the general practitioners in daily practice. This limited effect did not accord with the results of a pre- and post-workshop questionnaire evaluating the attitudes of the same practitioners. CONCLUSION: A single workshop can not effectuate substantial changes in prescription behaviors. Possibilities for more reinforcements are discussed. PMID- 11199239 TI - Is hands-on experience more effective than didactic workshops in postgraduate cancer pain education? AB - BACKGROUND: This study examined the nurse outcomes of a cancer pain education program for nurses of patients from 11 different ethnic groups. METHODS: Four hundred ninety six home, hospital, and hospice nurses participated in a one-day workshop or two half-day workshops on cancer pain assessment and management. Of these, 116 were randomized to participate in a bedside-precepted visit with an oncology nurse specialist with pain specialization and a focus group to discuss attitudinal issues. Eighty-six nurses served as controls. Pre-, post- and one year follow-up tests were administered. RESULTS: Attitudes, knowledge, and application skills significantly improved for workshop-only and enriched-model nurses relative to controls. CONCLUSION: For postgraduate nurses, daylong cancer pain education workshops were, in the group studied, as effective as hands-on experience in improving cancer pain knowledge and changing attitudes. Both the workshop-only and the enriched-model nurses relative to controls had significantly improved knowledge and changed attitudes towards optimal pain management. PMID- 11199240 TI - The effect of timing of the provision of information on anxiety and satisfaction of cancer patients receiving radiotherapy. AB - BACKGROUND: To improve the provision of information to their radiotherapy patients, the authors examined whether the timing of given written information has an effect on anxiety and satisfaction. METHODS: Two sources of information were used: 1) a booklet with a description of radiotherapy procedures and the sensations patients can experience; 2) teaching sheets with treatment-site related information. 68 patients were randomized to a simultaneous-information group (n = 31) and a stepwise-information group (n = 37). The patients were being treated for cancers of the breast, lung, head, and neck or the pelvic region. The authors analyzed the impacts of several variables on patient learning, including anxiety, age, gender, support, referral, stage of illness, and diagnosis. Assessments were recorded before the simulation procedure and during the second and last weeks of treatment. RESULTS: The stepwise-information group was significantly less anxious before simulation (p = 0.02) and more satisfied (p = 0.001). Of the variables studied, only the support variable was associated with high state anxiety (p < 0.0001). CONCLUSIONS: Provision of patient information in a stepwise format leads to less treatment-related anxiety and greater patient satisfaction among radiation therapy patient undergoing simulation. PMID- 11199241 TI - Adolescent girls' knowledge of and attitudes toward breast self-examination: evaluating an outreach education program. AB - BACKGROUND: The purpose of the study was to analyze the effectiveness of a one hour educational intervention to increase knowledge about and improve attitudes towards breast self-examination (BSE) and early cancer detection among adolescent girls. METHODS: The sample used in this quasi-experimental study was selected from schools participating in an education program provided by a regional health education center. The instrument and scales used in the study were developed and pilot-tested for reliability and validity in the area schools prior to the start of the study. The sample consisted of 137 adolescent girls who provided consent forms and participated in the intervention. The comparison group, which consisted of students attending the same schools, was scheduled to receive the intervention at a later date. RESULTS AND CONCLUSIONS: Findings suggest that a one-hour lesson can improve knowledge and attitudes of adolescent girls with respect to BSE and early cancer detection. Suggestions for further research are discussed. PMID- 11199242 TI - Impact of a cancer education multimedia device on public knowledge, attitudes, and behaviors: a controlled intervention study in Southern Sweden. AB - BACKGROUND: The objective was to determine the impact of a multimedia device offering information about malignant melanoma on public knowledge, attitudes, and behaviors. METHODS: Two municipalities in Sweden, Dalby and S Sandby, were chosen. The population of Dalby was exposed to the multimedia program during 1994 97, whereas the S Sandby population was not. A questionnaire was sent to random samples of the populations (10% of those aged 20-59 years) before (1994, n = 373 and n = 409, respectively) and after the intervention (1996, n = 375 and n = 418, respectively). Response rates were 74-89%. RESULTS: The groups were well balanced at baseline. In both areas women scored higher both at baseline and in 1996. Dalby women showed less fear of skin cancer in 1996 than in 1994 (2.13 vs 2.27, p < 0.01). This was not so in the controls. There was no major change in "sun behavior" in Dalby, whereas there was a negative change in S Sandby. After the intervention Dalby men had more "knowledge" (from 2.64 to 2.70, p < 0.05) and a tendency to better "sun behavior" (from 1.77 to 1.85, p = 0.076). There was no significant change over time in the S Sandby men. CONCLUSIONS: The multimedia program had a modest effect. The population in Dalby had more knowledge and changed its attitudes in a sun-protective direction. In the control area, the two year follow-up sun behavior score was lower than at baseline. There was also significantly less fear of skin cancer after the intervention. PMID- 11199243 TI - Tailored, interactive soap operas for breast cancer education of high-risk Hispanic women. AB - BACKGROUND: While Hispanic women have lower rates of breast cancer than do women of other ethnic groups, they are the least likely to undergo screening examinations. This study evaluated a culturally sensitive and linguistically appropriate, tailored, computer-based, educational program for early detection of breast cancer aimed at high-risk Hispanic women. METHODS: Spanish-speaking Hispanic women from an inner-city community health clinic were recruited and randomly assigned either to a computer intervention with an interactive soap opera format (n = 118) or to a comparison group (n = 60). Pre- and posttests were used to identify any change in breast-cancer-related knowledge and beliefs. RESULTS: Both younger (18-40 years old) and older (41-65 years old) women in the intervention group demonstrated significant increases in their breast cancer screening knowledge and beliefs as compared with the younger and older women in the comparison group (n < 0.05). CONCLUSIONS: Computer-based tailored and interactive soap operas that are linguistically and culturally appropriate are effective in increasing breast cancer screening knowledge and beliefs among underserved Spanish-speaking Hispanic women. PMID- 11199244 TI - Thoughts from a medical oncologist/teacher. PMID- 11199245 TI - Inspiration from a forum arranged by students. PMID- 11199246 TI - Shiftwork and cardiovascular disease: review of disease mechanisms. AB - This paper reviews the main findings concerning mechanisms explaining the increased risk of coronary heart disease (CHD) in shiftworkers. We discuss a conceptual model, in which three main shiftwork pathways to CHD are postulated- social problems, behavioral change, and disturbed circadian rhythm. Social problems that are associated with shiftwork might lead to stress. Significant shiftwork-related behavioral problems are smoking and unhealthy food habits. Disturbed circadian rhythm might result in sleep deprivation. Unphysiologic timing of physical activity and food intake in relation to circadian rhythms is another possible explanation for the negative impact on the cardiovascular system. PMID- 11199247 TI - The effect of high ambient temperature on the adjustment of operators to fast rotating 12-hour shiftwork. AB - The aim of the investigation was to study the effect of high ambient temperature (HAT) on the adjustment to fast rotating 12-h shifts by following the time-of-day variations of certain circadian and stress indicators. We investigated 12 male HAT operators and 21 individuals working in normal ambient temperature (NAT) in a thermoelectric power plant. The shift system of both groups comprised an 8-day cycle of 2 shifts per day (day shift: 0700 to 1900; night shift: 1900 to 0700), with 2 successive days of the same shift followed by 2 days off. We followed variations in oral temperature, 11-oxycorticoids, as well as catecholamines adrenaline and noradrenaline excretion at 4-h intervals during 2 day and 2 night shifts. Our data show daily oriented circadian rhythms of operators working on fast rotating 12-h shifts in conditions of HAT and NAT. Reduced general activation was observed in the second half of the prolonged 12-h night shifts, more pronounced in HAT operators. The stress indicators investigated here showed a stress reaction in HAT operators at the beginning of the first day shift. Both prolonged 12-h shifts and high ambient temperature impose extra demands and may have an impact on the performance and work safety of the operators. PMID- 11199248 TI - The use of epidemiological data to direct resources in food safety control. AB - In the United States, food-borne disease results in financial losses estimated at $2.9 to $6.7 billion annually as a result of illness that is due to six specific food-borne pathogens. A model is proposed that analyzes epidemiological data and highlights areas in food safety control that have the greatest impact on food borne disease. The model identifies Critical Control Points for use by the food industry, prioritizes criteria for inspection of food processes by regulatory authorities, and provides a focus for food hygiene training programs and campaigns. The model also provides a cost-benefit analysis that can be used to direct resources that are used in food safety control in a cost-effective manner. PMID- 11199249 TI - Somatotype, nutrition, and obesity. AB - The purpose of this investigation is to evaluate the somatotype characteristics of the studied group and search for a relation between somatotype, obesity, and particular features of nutrition. METHODS: Somatotype after Health & Carter (1990), nutritional status according to Body mass index (BMI), and nutrition determined by food-frequency questionnaires. RESULTS: Over 94% of the subjects in this study were distributed into five somatotype categories: 51.6% endomorphic mesomorphs, 17.1% mesomorph-endomorphs, 16.7% mesomorphic endomorphs, 6.1% balanced mesomorphs, and 3.0% ectomorphic mesomorphs, with a pronounced sexual dimorphism. Males were distributed into five categories: over 65% were endomorphic mesomorphs, and above 40 years of age the mesomorphy increased. Females were distributed into three somatotype categories: up to and above 40 years of age over 44% were mesomorphic endomorphs. In the most common somatotype categories, 1 of 5 subjects (from 21.4% to 19.9%) had normal body mass (< 25 kg/m2), 4 of 5 subjects (from 34.2% to 52.6%) were overweight (> 25 kg/m2) or obese (> 30 kg/m2) kg/m2 (from 44.4% to 27.5%). In the remaining eight categories, all subjects had normal body mass. Hyperenergetic, sodium- and fat excess nutrition had an especially unfavorable influence. PMID- 11199250 TI - Impact of pesticides use on human health in Mexico: a review. AB - Pesticides having a high adverse effect on the health and environment of inhabitants of the Mexican Republic were studied to establish the main parameters to bear in mind for their use and application. The investigation showed that Mexico is the agricultural zone with the highest health damage to its population from pesticides. The valid regulation norms for the use and application of these agrochemicals were analyzed. Case histories recorded by the public health sector in Mexico were reviewed. In this way, a strong relation was found between the health problems and the pesticides applied. Finally, the study concludes that the various Mexican States appear as a risk zone because of contamination by pesticides that are permitted by the regulation norms and by others whose use is prohibited in other countries and in Mexico. This situation causes a serious effect on the health deterioration of people who are exposed to these agro chemicals and, in some cases, leads to death. PMID- 11199251 TI - Environmental exposure to manganese and combined exposure to gaseous upper respiratory irritants: mechanism of action and adverse health effects. AB - This review relates to possible explanations of the often-observed findings that exposure to certain air pollutants or their mixture results in an increased rate of acute respiratory diseases. Epidemiological investigations have shown that exposure to manganese (MnO2) concentrations only 10 to 50 times higher than the normal urban concentrations of 0.01 to 0.03 microgram/m3 air might have an adverse health effect on respiratory organs. The assumption that one possible mechanism of action could be that manganese at such exposure levels disturbs certain protective functions in the lung--thus making the organism more susceptible to infections--is supported by toxicological studies. In vitro studies have demonstrated the cytotoxic action of manganese, including the inhibition of activities of alveolar macrophages. Animal experiments showed a decrease in resistance toward respiratory infections that were caused by simultaneous exposure to MnO2 and pathogenic bacteria. In cases of combined exposure to gaseous upper respiratory tract irritants and suspended particles, the involvement of adsorption of gaseous compounds on solid particles as carriers has been suggested. The assumption is that through such a mechanism, water soluble gaseous irritants can be transported deep into air passages, which such irritants normally do not reach. As the adsorption is reversible, the gaseous compounds can later be released from the particles, inducing a local irritating effect in the small airways and alveoli. PMID- 11199252 TI - Chlorpyrifos: an unwelcome pesticide in our homes. AB - Chlorpyrifos is an extensively used organophosphate insecticide having many urban and agricultural crop pest control uses. Studies conducted in indoor environments after termiticide, crack-and-crevice, broadcast, or fogger applications have shown that chlorpyrifos exposure can occur via inhalation of residual air concentrations, dermal or oral exposure from residues on floors and carpets, children toys, food, and dust. Not long ago the weight of scientific evidence supported safe indoor use, but recent studies support the possibility that when pregnant female rats are given the pesticide, chlorpyrifos causes brain damage in fetal rats. Moreover, the exposure of young rats to chlorpyrifos impairs early nervous system development. After finding that chlorpyrifos is an exposure risk especially to children, in June 2000 the United States Environmental Protection Agency and manufacturers agreed to voluntary measures that will reduce the exposure of children to chlorpyrifos-containing products. This action implies a search for less harmful new products to replace it and/or safer ways to control pests through basic hygiene. Whichever pest control method is selected, one should keep in mind that preventing environmental pesticide exposure in children is always better than treating the resulting disease. PMID- 11199253 TI - Differences in psychological and physical health among layoff survivors: the effect of layoff contact. AB - This study examined health and well-being among workers who have experienced varying types of contact with layoffs in an organization undergoing downsizing. Using survey data from a large organization employing both white- and blue-collar workers (N = 2,279), the authors argued that there are important differences among surviving workers as a function of their layoff experiences. Having any kind of personal contact with layoffs is found to be associated with less job security, more symptoms of poor health, depression, and eating changes as compared with having no layoff contact. Being laid off and rehired is associated with more work-related injuries and illnesses and missed work days due to such events than is receiving a "warn" notice, indirect contact (i.e., friends or coworkers laid off), or no contact with layoffs. Job security partially mediates the relationship between type of layoff contact experiences and health. PMID- 11199254 TI - Job insecurity in white-collar workers: toward an explanation of associations with health. AB - This article describes 2 studies that examined changes in psychosocial work characteristics (job strain model) and health-related behaviors as potential explanations of the job insecurity-health relationship in a longitudinal cohort of white-collar British civil servants. Job insecurity arising from anticipation of change was associated with a modest increase in self-reported morbidity, whereas chronic job insecurity was associated with some adverse physiological changes. Anticipation of change and chronic job insecurity were associated with adverse changes in other psychosocial work characteristics, but few changes were significant and consistent across both exposure groups. Changes in health-related behaviors associated with either exposure were slight. Apart from a minor role for social support at work in both sexes and a modest role for job demands in women, adverse changes in these factors explain little of the job insecurity health relationship. PMID- 11199255 TI - Changes in general health and musculoskeletal outcomes in the workforce of a hospital undergoing rapid change: a longitudinal study. AB - This article aimed to examine changes in general health and time with back pain and neck pain and to identify predictors of any such changes. Hospital workers were studied longitudinally with surveys in 1995, 1996, and 1997 (N = 712). Back and neck pain were reported only at the 2nd and 3rd surveys. There was a significant decline in general health and significant increases in time with neck pain and back pain. Predictors of changes in these outcomes were mainly work related variables (initial or change values), such as job interference with family, job influence, work psychological demands, and hours worked. PMID- 11199256 TI - Burnout and inequity among human service professionals: a longitudinal study. AB - In a composite sample of human service professionals (N = 245), longitudinal relations across 1 year were tested between equity in the professional-recipient relationship and burnout (i.e., emotional exhaustion, depersonalization, and reduced personal accomplishment). The 1st research question was whether inequity influenced burnout across time. The 2nd research question was whether longitudinal relations between equity and burnout were curvilinear, as predicted by equity theory. The results confirmed that inequity affects the central component of burnout (i.e., emotional exhaustion) and that this relation is curvilinear. Feeling more deprived and feeling more advantaged resulted in higher future emotional exhaustion levels. No indication was found for a longitudinal relation between inequity and depersonalization. A synchronous relation was found suggesting that personal accomplishment influences equity. PMID- 11199257 TI - Deriving benefits from stressful events: the role of engagement in meaningful work and hardiness. AB - This research explored the relationship between the meaningfulness of work, personality hardiness, and deriving long-term benefits from a stressful event. U.S. soldiers participating in a peacekeeping mission to Bosnia completed measures assessing the meaning of their work and personality hardiness midway through a 1-year deployment (mid-deployment) and completed a measure of deriving benefits from the deployment 4-5 months after it was over (postdeployment). Structural equation modeling revealed that personality hardiness was associated with being engaged in meaningful work during the deployment, which was strongly associated with deriving benefits from the deployment months after it was over. Enriching experiences were also associated with deriving benefits from the deployment. Discussion focuses on the linkages between personality processes, meaningful work, and deriving benefits from a stressful experience. PMID- 11199258 TI - Incivility in the workplace: incidence and impact. AB - This study extends the literature on interpersonal mistreatment in the workplace by examining the incidence, targets, instigators, and impact of incivility (e.g., disrespect, condescension, degradation). Data were collected from 1,180 public sector employees, 71% of whom reported some experience of workplace incivility in the previous 5 years. As many as one third of the most powerful individuals within the organization instigated these uncivil acts. Although women endured greater frequencies of incivility than did men, both genders experienced similarly negative effects on job satisfaction, job withdrawal, and career salience. Uncivil workplace experiences were also associated with greater psychological distress; however, indices of psychological and physical health were relatively unaffected. The authors discuss these findings in the context of organizational and cognitive stress theories. PMID- 11199259 TI - Critters in the cube farm: perceived psychological and organizational effects of pets in the workplace. AB - This article reports the findings of an exploratory study examining the perceived functions and psychological and organizational effects of pets in the workplace. Participants were 193 employees from 31 companies allowing pets in the workplace who completed anonymous questionnaires. Results indicated that participants perceived pets in the workplace to reduce stress and to positively affect employee health and the organization. Participants who brought their pets to work perceived greater benefits than participants who did not bring their pets to work and participants who did not own pets. PMID- 11199260 TI - Hybrid vector designs to control the delivery, fate and expression of transgenes. AB - One of the greatest challenges to gene therapy is the targetting of gene delivery selectively to the sites of disease and regulation of transgene expression without adverse effects. Ultimately, the successful realization of these goals is dependent upon improvements in vector design. Over the years, viral vector design has progressed from various types of replication-defective viral mutants to replication-conditioned viruses and, more recently, to 'gutted' and hybrid vectors, which have, respectively, eliminated expression of non-relevant or toxic viral genes and incorporated desired elements of different viruses so as to increase the efficacy of gene delivery in vivo. This review will focus on the different viral and cellular elements which have been incorporated into virus vectors to: improve transduction efficiencies; alter the entry specificity of virions; control the fate of transgenes in the host cells; and regulate transgene expression. PMID- 11199261 TI - MLV-10A1 retrovirus pseudotype efficiently transduces primary human CD4+ T lymphocytes. AB - BACKGROUND: Previously, we showed that retroviral vectors pseudotyped with the envelope of the amphotropic murine leukemia virus 10A1 (MLV-10A1) more efficiently transduce primary human CD8+ T lymphocytes when compared with other A MLV, gibbon ape leukemia virus (GaLV) and feline endogenous retrovirus (RD114) vector pseudotypes. For the success of several gene therapeutic approaches (ADA, HIV) it is important to effectively transduce primary human CD4+ T lymphocytes. METHODS: We have used retroviral vectors encoding the enhanced green fluorescent protein (EGFP) as a marker gene and carrying envelopes of MLV-10A1, A-MLV and GaLV and have analyzed the transduction efficiency of both human CD4+ T cell lines (CEM, H9, HUT78, J16) and primary human CD4+ T lymphocytes using a RetroNectin-assisted transduction protocol and virus-containing supernatant. RESULTS: In CD4+ T cell lines the MLV-10A1 vector pseudotype was most effective and infected up to 85% of cells which then stably expressed GFP over time. MLV 10A1 was also superior and infected approximately 32% of primary human CD4+ T lymphocytes in comparison to GaLV (18%) and A-MLV (12%). The superior efficiency of MLV-10A1 for the transduction of CD4+ T cells correlates with the longer half life of this pseudotype in comparison to A-MLV and, as previously shown by interference analysis, with the usage of both the A-MLV (Pit2) and the GaLV receptor (Pitl) for cell entry. CONCLUSIONS: MLV-10A1 is a suitable vector for transferring genes with high efficacy into primary human CD4+ T lymphocytes. The use of MLV-10A1 pseudotyped vectors should make it easier to obtain a sufficient number of gene-modified T lymphocytes for an adoptive transfer. PMID- 11199262 TI - T cell-specific expression from Mo-MLV retroviral vectors containing a CD4 mini promoter/enhancer. AB - BACKGROUND: Gene therapy of various immunological disorders will greatly benefit from improved retroviral vectors (RVs) with T cell specificity. Such vectors can be designed by placing a gene of therapeutic interest under the control of tissue specific transcriptional elements. However, low titers and loss of specificity are frequently encountered with tissue-specific vectors. The aim of the present study was to develop a T cell-specific RV. METHODS: We constructed a series of Moloney murine leukemia virus (Mo-MLV)-based RVs expressing enhanced green fluorescent protein (EGFP) under the control of a mini-promoter/enhancer cassette derived from the CD4 gene (CD4pmE) and tested them in cell lines and peripheral blood lymphocytes. Expression of EGFP was monitored by fluorescence microscopy and analyzed by flow cytometry. RESULTS: The CD4pmE cassette was inserted between the viral long terminal repeats (LTRs) in self-inactivating vectors (SIN vectors) or was substituted to the 3' U3 viral promoter/enhancer (hybrid vectors). High vector titers but poor specific expression of EGFP were achieved when CD4pmE was inserted in sense orientation in SIN vectors. Low titers but high specificity were observed when the CD4pmE cassette was in anti-sense orientation. In contrast, high titers and good T cell specificity were obtained with hybrid vectors. CONCLUSION: An efficient T cell-specific retroviral vector was obtained. PMID- 11199263 TI - p53 adenoviral vector (Ad-CMV-p53) induced prostatic growth inhibition of primary cultures of human prostate and an experimental rat model. AB - BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common proliferative disease affecting men. Numerous minimally invasive technologies are being developed or are currently in use to obviate the need for transurethral surgery. The goal of the present study was to develop a novel molecular based approach for the treatment of BPH using recombinant p53 adenoviral vector. The over-expression of wt-p53 can cause cell apoptosis or cell growth arrest, thus preventing the uncontrolled cell proliferation underlying BPH pathophysiology. METHODS: Ad-CMV p53, a replication-deficient recombinant adenovirus containing cytomegalovirus promoter driving p53 gene, was used. Human prostate stromal (PS) cells were evaluated for apoptosis (TUNEL assay), mRNA levels of key cell cycle regulators influencing apoptosis (p-53, Bax and Bcl-2) using quantitative RT-PCR and cytotoxicity after Ad-CMV-p53. Ad-CMV-p53 was unilaterally injected into rat ventral prostates and growth inhibition was measured by prostate weight 3 weeks after injection. RESULTS: In vitro exposure to Ad-CMV-p53 significantly inhibited the proliferation of PS cells, induced mRNA over-expression of both wt-p53 and Bax, and increased the proportion of apoptotic cells. A 30% decrease in average prostate weight was demonstrated in rodents after Ad-CMV-p53 injection. CONCLUSIONS: The results suggest that further investigation of molecular gene therapy with recombinant wt-p53 adenovirus for the treatment of BPH is warranted. PMID- 11199264 TI - Differential influence of the E4 adenoviral genes on viral and cellular promoters. AB - BACKGROUND: Strong and stable transgene expression is fundamental to the success of recombinant adenovirus vectors in human gene therapy. However, control of transgene expression is a complex process, involving both viral and cellular factors. In this study, the influence of the E4 adenoviral region on the activity of various promoters was investigated in vitro and in vivo. METHODS: Pairs of isogenic E1o and E1oE4o vectors were generated and compared. Levels of transgene expression were determined by Northern blot, ELISA and FACS analysis. Initiation of transcription was studied by nuclear run-on assays. RESULTS: Similar to the viral CMV and RSV promoters, the activity of the ubiquitous cellular PGK promoter required the presence of the E4 genes in vitro and in vivo. In contrast, transgene expression from selected liver- and tumor-specific promoters did not require E4 functions. CONCLUSION: Together with the reported low liver toxicity of E1oE4o vectors, the independence of E4 of liver-specific promoters renders such vectors interesting alternatives to the use of gutless vectors. PMID- 11199265 TI - Scaleable chromatographic purification process for recombinant adeno-associated virus (rAAV). AB - BACKGROUND: Adeno-associated virus (AAV) is a human parvovirus currently being developed as a vector for gene therapy applications. Traditionally AAV has been purified from cell lysates using CsCl gradients; this approach however is not likely to be useful in large-scale manufacturing. Moreover gradient-purified AAV vectors tend to be contaminated with significant levels of cellular and adenoviral proteins and nucleic acid. To address the issue of purification we have developed a process scale method for the rapid and efficient purification of recombinant AAV (rAAV) from crude cellular lysates. METHODS: The preferred method for the purification of rAAVbetagal includes treatment of virally infected cell lysates with both trypsin and nuclease followed by ion exchange chromatography using ceramic hydroxyapatite and DEAE-Sepharose in combination with cellufine sulphate affinity chromatography. RESULTS: Purification of rAAV particles from crude cellular lysates co-infected with adenovirus was achieved using column chromatography exclusively. Column-purified rAAV was shown to be greater than 90% pure, free of any detectable contaminating adenovirus, biologically active, and capable of directing efficient gene transfer to the lungs of both cotton rats and mice. CONCLUSIONS: This study demonstrates the feasibility of using column chromatography alone for the isolation of highly purified rAAV vector. The methods described here are advancements in procedures to purify rAAV and are adaptable for commercial production of clinical-grade rAAV vector. PMID- 11199266 TI - An optimized amphiphilic cationic peptide as an efficient non-viral gene delivery vector. AB - BACKGROUND: Due to their chemical definition and reduced size, the use of peptides as gene delivery systems is gaining interest as compared to the more common polymeric non-viral vectors. To achieve gene transfer efficiencies that would make peptides a realistic alternative to existing methods, we have evaluated and attempted to concert those properties with a direct impact on the activity of the system. These considerations have led to the design, synthesis and characterization of a 23-residue cationic peptide which we term RAWA. METHODS: We have characterized RAWA biophysically and functionally. Biophysical studies include evaluation of DNA condensation and membrane perturbing activities. DNA transfer activity has been evaluated in cell culture at controlled DNA-to-peptide stoichiometries, using a luciferase gene as reporter. Requirements for additional effectors such as chloroquine and peptide cofactors have also been considered. RESULTS: RAWA displays in vitro DNA condensing activity similar to that of protamines, reaching maximum effect at a peptide-to DNA molar charge ratio (CR) of 4 (+/-). The reduced membrane perturbing activity diminishes its cytotoxic potential. In COS-7 cells, transfection efficiency with RAWA peptiplexes, compares favorably with well-recognized systems, including Lipofectamine Plus, Superfect, GenePorter and FuGene. The peptide-associated activity between free and DNA-bound species has been mapped by analyzing dependency on chloroquine treatment. The lack of significant serum inhibition and low toxicity make this system advantageous for potential in vivo application. A ternary complex including the acid-triggered fusogenic JTS-1 peptide is presented as a potential strategy for further in vivo studies. CONCLUSIONS: We have developed a gene delivery system based on an amphipathic cationic peptide with improved DNA condensation ability and reduced cytotoxicity, which maintains membrane binding and perturbing activities. Observed efficiency with this molecule is very high and compares favorably with currently available transfection systems. PMID- 11199267 TI - Serum as a modulator of lipoplex-mediated gene transfection: dependence of amphiphile, cell type and complex stability. AB - BACKGROUND: Cationic liposomes belong to the family of non-viral vectors for gene delivery. Despite several drawbacks, such as low efficiency compared to viruses and inactivation by serum, cationic liposomes remain a promising tool for gene therapy. Therefore further investigation of the mechanism of transfection and improvement of formulations are warranted. METHOD: In a comparative study, we investigated the effect of serum on the ability of SAINT, a novel synthetic amphiphile, and Lipofectin to mediate transfection in vitro, employing a variety of cell lines. RESULTS: In all cell types, SAINT-mediated transfection was not significantly affected by the presence of serum, in contrast to Lipofectin mediated transfection. Intriguingly, the extent of complex association was enhanced in the presence of serum, while cell association of the Lipofectin complex was approximately two-fold higher than that of SAINT. These data imply that transfection efficiency and the amount of cell-associated complex are not related. However, when the helper lipid dioleoylphosphatidylethanolamine (DOPE) was substituted for cholesterol, SAINT-mediated transfection was reduced in the presence of serum. This indicates that lipoplex composition rather than the cationic lipid per se codetermines the effect of serum. Also, the presence of serum decreased cytotoxicity, while no correlation could be demonstrated between toxicity and transfection efficiency. The binding of serum proteins to either complex was identical, both in terms of protein identity and relative amounts. CONCLUSION: We propose that serum, in conjunction with cell-specific factors and lipoplex composition, determines complex (in)stability, which is crucial for effective gene delivery and expression. PMID- 11199268 TI - Role of endosomes in gene transfection mediated by photochemical internalisation (PCI). AB - BACKGROUND: Most non-viral gene therapy vectors deliver transgenes into cells through the endocytic pathway. Lack of escape from endocytic vesicles in many cases constitutes a major barrier for delivery of the functional gene. We have developed a new technology named photochemical internalisation (PCI) to achieve light-inducible cytosolic delivery of the transgene. The technology is based on a photochemical treatment employing photosensitisers localised in endocytic vesicles. In this work mechanisms involved in PCI-mediated transfection (photochemical transfection) were studied. METHODS: Human melanoma or colon carcinoma cells were pre-incubated with the photosensitiser aluminium phthalocyanine disulfonate (AlPcS2a) followed by treatment with plasmid encoding enhanced green fluorescent protein (EGFP) complexed with poly-L-lysine, N-(1-(2,3 dioleoxyloxy)propyl)-N,N,N,-trimethylammonium-methyl-sulfate (DOTAP) or polyethylenimine (PEI) and light exposure. The expression of the EGFP-gene was scored by fluorescence microscopy and flow cytometry. RESULTS: The photochemical treatment using light doses corresponding to D50 substantially improves the efficiency of transfection mediated by poly-L-lysine and PEI, but not by DOTAP. The treatment does not enhance the delivery of the plasmid complex across the plasma membrane, since the amount of internalised plasmid is similar for irradiated and non-irradiated cells. Light-inducible transfection occurs only under temperature conditions allowing endocytic uptake and is not improved by chloroquine or ammonium chloride, but is inhibited by bafilomycin A1 (agents that increase vesicular pH and interfere with the endocytic transport). CONCLUSIONS: Photochemical transfection occurs through endocytosis, followed by cytosolic release of the transfecting DNA from photochemically permeabilised endocytic vesicles. Release of plasmid from early endosomes seems to be of importance in photochemical transfection, although a role of later endocytic vesicles can, however, not be ruled out. PMID- 11199269 TI - Alcohol, the brain, and behavior. Mechanisms of addiction. AB - The actions of alcohol that cause intoxication, initiate and maintain excessive drinking behavior, and promote relapse during abstinence occur primarily in the brain. A thorough understanding of alcohol's effects on the mechanisms underlying brain function is essential to develop and improve alcoholism prevention and treatment strategies. This article is not an exhaustive overview of alcoholism neurobiology, but a sampling of the more significant recent advances in the field. PMID- 11199270 TI - Why do some people drink too much? The role of genetic and psychosocial influences. AB - A sizable minority of the population abuses alcohol. Research has found that some vulnerability to developing alcohol-related problems is conveyed genetically, and animal research has indicated that inheritance can take many forms. Studies in mice have demonstrated that various individual genes or groups of genes can shape very distinct responses to alcohol. By identifying the proteins these genes encode and the mechanisms by which the genes influence an animal's biochemical response to alcohol, scientists can gain insight into the features of human alcoholism and provide a basis for developing pharmaceuticals that short-circuit these genetically defined processes. PMID- 11199271 TI - Medical consequences of alcohol abuse. AB - Studies have shown that long-term alcohol abuse produces serious, harmful effects on a variety of the body's organ systems. Parts of the human body most affected include the liver and the immune, cardiovascular, and skeletal systems. Current research has examined some of these effects in an effort to better understand the medical consequences of alcohol use and abuse and to ultimately develop more effective treatments for responding to alcohol-induced bodily damage. This article discusses some of those findings. PMID- 11199272 TI - Prenatal exposure to alcohol. AB - Maternal alcohol consumption during pregnancy can cause serious birth defects, of which fetal alcohol syndrome (FAS) is the most devastating. Recognizable by characteristic craniofacial abnormalities and growth deficiency, this condition includes severe alcohol-induced damage to the developing brain. FAS children experience deficits in intellectual functioning; difficulties in learning, memory, problem-solving, and attention; and difficulties with mental health and social interactions. An FAS diagnosis, however, fails to identify prenatal alcohol-exposed children who lack the characteristic facial defects and growth deficiency of FAS. Nonetheless, these often undiagnosed children may still experience serious fetal alcohol effects (FAE), including alcohol-induced mental impairments (i.e., alcohol-related neurodevelopment disorder) or alcohol-related abnormalities of the skeleton and certain organ systems (i.e., alcohol-related birth defects). Neuroimaging techniques can assist researchers in identifying FAE through precise pictures of brain abnormalities in persons prenatally exposed to alcohol. By understanding the mechanisms underlying FAE and the behavioral manifestations of the resulting structural brain damage, researchers can ultimately develop effective FAS prevention strategies that identify and assist high-risk women at varying levels of pregnancy. PMID- 11199273 TI - Latest approaches to preventing alcohol abuse and alcoholism. AB - Scientists and policymakers have explored numerous strategies to prevent alcohol abuse and dependence as well as the adverse social, legal, and medical consequences of alcohol use. Many of these efforts have focused on reducing alcohol-impaired driving and the associated injuries and fatalities. As reported in this article, such efforts have included general deterrence laws (e.g., reduced minimum legal drinking age, administrative license revocation, and lower legal limits for blood alcohol concentrations), measures targeted at repeat offenders, and measures to control alcohol availability (e.g., increased taxes and decreased numbers of establishments selling alcohol). PMID- 11199274 TI - Health risks and benefits of alcohol consumption. AB - Alcohol consumption has consequences for the health and well-being of those who drink and, by extension, the lives of those around them. The research reviewed here represents a wide spectrum of approaches to understanding the risks and benefits of alcohol consumption. These research findings can help shape the efforts of communities to reduce the negative consequences of alcohol consumption, assist health practitioners in advising consumers, and help individuals make informed decisions about drinking. PMID- 11199275 TI - Research refines alcoholism treatment options. AB - Every day, more than 700,000 people in the United States receive treatment for alcoholism. In recent years, much progress has been made in understanding how both psychological approaches and medications can help these patients achieve sobriety, including evaluation of existing treatment approaches and development of new ones. Continued research to refine therapies for alcoholism will have widespread benefits for alcohol-dependent people, for their families, and for society as a whole, which bears the weight of the enormous economic and social costs of problem drinking. This article reviews the current state of alcoholism treatment research. PMID- 11199276 TI - Economic analysis aids alcohol research. AB - Economic research contributes to our understanding of alcohol use and the prevention and treatment of alcohol-related problems in several ways. This article reviews three areas in which the tools of economic analysis have produced significant insights in recent years. First, economic researchers have analyzed the effects of beverage prices and taxation on alcohol consumption and on adverse consequences associated with alcohol use. Second, analyses of the costs and cost effectiveness of treatment for alcohol use disorders have provided insight into the long-term costs and benefits of alternative approaches to alcoholism treatment. Finally, studies have incorporated economic techniques in estimating the overall magnitude of the burden placed on society by the misuse of alcoholic beverages. PMID- 11199277 TI - Animal models of alcohol withdrawal. AB - One diagnostic criterion of alcohol dependence is the appearance of a withdrawal syndrome when alcohol consumption ceases. Researchers have used various animal models, including isolated brain cells, slices of brain tissue, and intact animals, to study the mechanisms and manifestations of withdrawal. Results from these experimental studies have demonstrated that many consequences of withdrawal found in animals resemble those observed in humans. Such signs and symptoms of alcohol withdrawal include enhanced activity of the autonomic nervous system; body posture and motor abnormalities; hyperexcitability of the central nervous system, including sensory hyperreactivity; convulsions; anxiety; and psychological discomfort. Researchers also have used animal models to study the electrophysiological correlates of withdrawal, as well as neurobiological mechanisms underlying alcohol dependence and withdrawal. PMID- 11199278 TI - Modeling adolescent development and alcohol use in animals. AB - Though certain characteristics found in human adolescents are clearly unique, there are other key characteristics of this developmental stage that are common across a number of species. Animal models offer researchers unique insight into the effects of alcohol on the adolescent. This age period is particularly important for study, because this is the time during which many people first experiment with alcohol. It is possible that features of the adolescent brain may in fact predispose a youngster to behave in ways that place him or her at particular risk for experimenting with alcohol or other drugs. In addition to behavioral changes, a number of important physiological alterations occur during adolescence, including changes in brain regions implicated in modulating the reinforcing effects of alcohol and other drugs of abuse. PMID- 11199279 TI - Recent animal models of alcoholism. AB - Animal models on alcohol preference have a long-standing tradition in biomedical research on alcoholism. However, these models allow only limited conclusions regarding alcohol addiction. Therefore, during the past 15 years, researchers have developed new animal models that mimic different aspects of human alcohol addiction, such as craving, relapse, and loss of control over drinking. These models include the reinstatement model, the alcohol deprivation model, and the point-of-no-return model. Some of these models have been pharmacologically validated with anti-craving compounds that are used clinically for treating alcoholics. The detailed behavioral characterization of these new models and their pharmacological validation also allow researchers to study the neurochemical and molecular bases of addictive behavior. PMID- 11199280 TI - An economic approach to animal models of alcoholism. AB - Researchers have long sought an animal model for human alcohol consumption. This article describes an economic-based approach to a model of alcohol preference in rats. The procedures are based on an analogy between clinical accounts of human drinking and the economic analysis of consumption. Both clinical and economic investigators typically define consumption patterns in terms of the influence of negative consequences. For example, the clinical account emphasizes the persistence of heavy drinking despite mounting alcohol-related aversive consequences, and in economic analyses, the term "inelastic demand" is used to refer to the persistence of consumption despite large increases in prices. In the experimental procedure described here, rats worked for alcohol and food. Presses on one lever earned a drink of 10 percent alcohol plus saccharin, and presses on a second lever earned isocaloric drinks of a starch solution. After behavior stabilized, the response requirements (which are analogous to prices) for one or both drinks were increased. The rats maintained baseline alcohol consumption levels despite large increases in the "price" of alcohol. In contrast, the same price increases markedly reduced starch intake. That is, food consumption was sensitive to price hikes, but alcohol consumption was not. The results demonstrate that a common economic framework can be used to describe human and animal behavior and, hence, the possibility of an animal model of human alcohol consumption. The article also points out that economic concepts provide a framework for understanding a wide range of human drinking patterns, including controlled social drinking and excessive alcoholic drinking. PMID- 11199281 TI - Animal models in alcohol research. AB - Animal models are important tools in the study of alcohol use, abuse, and dependence because they allow researchers to use methods that cannot be used with human subjects. Animal models have been developed to study various aspects of alcohol use and dependence, including alcohol-seeking behavior, alcohol-related organ damage, tolerance to alcohol, and physical dependence on alcohol. Because animal models can be genetically manipulated, they are also valuable for research into the genetic determinants of alcoholism. Issues surrounding the use of animal models in alcohol research include the species of animal used, the method of alcohol administration, and the model's face and predictive validity. PMID- 11199282 TI - Animal models of alcohol's motivational effects. AB - Alcohol's positive and negative motivational effects are believed to be important influences on alcohol-seeking behavior and, therefore, key factors among the many and varied causes of alcohol abuse and dependence. Alcohol's positive effects, such as enhanced mood, and negative effects, such as hangover, are considered important factors in motivating drinkers to increase or decrease their drinking. Scientists have developed a variety of animal behavioral models to study alcohol's motivational effects. These models include "self-administration models," in which the animal controls the exposure to alcohol, and "conditioning models," in which the researcher controls the animal's exposure to alcohol. Such models have been used to study the influence of genetic differences on sensitivity to alcohol's positive and negative motivational effects, the brain mechanisms underlying alcohol's motivational effects, as well as relapse and craving. PMID- 11199283 TI - Modeling alcohol's effects on organs in animal models. AB - Researchers have developed numerous animal models to investigate the development of various alcohol-related diseases. Such models have provided insights into the mechanism through which alcohol can induce liver damage. Animal models also have helped researchers explore the mechanisms by which both short-term (e.g., binge) and long-term drinking can interfere with the function of the heart, a condition referred to as alcoholic cardiomyopathy. Furthermore, animal models have provided substantial information on the causes of fetal alcohol syndrome. Such models have demonstrated that exposure to alcohol during gestation can lead to prenatal and postnatal growth retardation, characteristic facial malformations, immune system deficiencies, and alterations in the central nervous system. PMID- 11199284 TI - Animal models of psychiatric disorders and their relevance to alcoholism. AB - Animal models are important tools in the study of psychiatric disorders, including alcoholism, because they allow the use of research methods that cannot be used for ethical reasons in humans. Consequently, scientists have developed numerous approaches to evaluate the validity and reliability of animal models for studying human behavior and human disorders. Researchers have developed animal models of schizophrenia, fear and anxiety, depression, and alcoholism, all of which are being used to study the relationship between alcoholism and co occurring psychiatric disorders. These models may help researchers and clinicians determine how best to treat patients with alcoholism and co-occurring psychiatric disorders. PMID- 11199285 TI - Selected lines and inbred strains. Tools in the hunt for the genes involved in alcoholism. AB - In their quest to elucidate the genetic influences contributing to alcoholism, researchers have long used selected lines and inbred strains of rodents. Selected lines are obtained by repeatedly mating those animals within a population that show extremely high or low values of the desired trait. Inbred strains are generated by mating male and female siblings, irrespective of any particular trait, over several generations. Both of these approaches have provided researchers with extensive knowledge about the genetic and neurobiological mechanisms contributing to alcohol-related traits. However, the use of these models is associated with some limitations, mostly resulting from the inbreeding involved in generating such lines and strains. Nevertheless, these models can offer some advantages over other genetic approaches, such as the analysis of quantitative trait loci or the generation of transgenic and knockout mice. PMID- 11199286 TI - The candidate gene approach. AB - Alcoholism has a significant genetic basis, and identifying genes that confer a susceptibility to alcoholism will aid clinicians in preventing and effectively treating the disease. One commonly used technique to identify genetic risk factors for complex disorders such as alcoholism is the candidate gene approach, which directly tests the effects of genetic variants of a potentially contributing gene in an association study. These studies, which may include members of an affected family or unrelated cases and controls, can be performed relatively quickly and inexpensively and may allow identification of genes with small effects. However, the candidate gene approach is limited by how much is known of the biology of the disease being investigated. As researchers identify potential candidate genes using animal studies or linking them to DNA regions implicated through other analyses, the candidate gene approach will continue to be commonly used. PMID- 11199287 TI - Quantitative trait locus analysis. AB - Alcoholism is a quantitative disorder that is caused by the combined influences of numerous genes (i.e., quantitative trait loci [QTLs]) and environmental factors. To identify QTLs for alcoholism, researchers compare subject groups (e.g., inbred mouse strains) that differ in both their genetic makeup (i.e., genotype) and alcohol-related trait (e.g., sensitivity to certain alcohol effects). Using statistical tests one can then determine whether a specific gene or DNA region contributes to the trait of interest. This strategy requires that the relevant gene exists in several variants (i.e., is polymorphic). To conduct such QTL analyses, researchers study either a large population of mice that all differ in their genotypes or compare several strains, each of which has a fixed genotype. However, QTL analyses still have several limitations. Nevertheless, such studies already have identified several DNA regions and genes that may affect the response to alcohol and thus may contribute to the risk for alcoholism. PMID- 11199288 TI - Applications of transgenic and knockout mice in alcohol research. AB - Multiple genetic and environmental factors contribute to the development of alcoholism. Researchers attempting to elucidate the roles of specific genes in alcoholism risk have benefited from advances in genetic engineering. Two important tools used by researchers include transgenic mice, in which a foreign gene is integrated into an animal's genetic material, and knockout/knock-in mice, in which targeted genes either are rendered nonfunctional or are altered. Both of these animal models are currently used in alcohol research to determine how genes may influence the development of alcoholism in humans. PMID- 11199289 TI - Genetics of alcohol-induced behaviors in Drosophila. AB - Researchers frequently study the fruit fly Drosophila melanogaster as a model system for mammalian development and behavior. Drosophila appear resistant to alcohol's toxic effects and display many behaviors resembling intoxication (e.g., impaired motor control) when exposed to alcohol vapors. Accordingly, investigators have begun to measure alcohol sensitivity in Drosophila and to identify genetic mutations associated with increased or decreased sensitivity. One mutant called cheapdate affects a signaling system that plays a role in many regulatory processes in a cell and which involves the compound cyclic adenosine monophosphate (cAMP). Additional Drosophila mutants with altered alcohol sensitivity carry mutations in other components of the cAMP signaling system. Because the cAMP system also is affected in human alcoholics, these results indicate that studies using Drosophila as a model system may identify genetic changes relevant to human alcoholism. PMID- 11199290 TI - Future directions in alcoholism research. Genomics and gene transfer. AB - Alcohol affects the process by which genes direct the synthesis of proteins (i.e., expression). Therefore, patterns of gene expression in the presence of alcohol can help scientists identify the specific molecular sites of alcohol's actions within the brain. New technologies can detect and quantify changes in the expression of thousands of genes simultaneously by scanning microscopic gene arrays applied to glass or silicon chips an inch or so square. However, genes whose activity is altered in the presence of alcohol may either be contributing to alcoholism development or may be reacting to alcohol's presence. This question can be researched by observing the effects of manipulating the level of specific gene products. One way to accomplish this end is by means of viruses that have been engineered to express a specific gene in infected cells. This technique has been applied successfully in studying addictive behaviors. It is suggested that patterns of gene expression may become a diagnostic tool, with different disease states being characterized by distinct expression profiles. PMID- 11199291 TI - Hyperbaric oxygen therapy in acute necrotizing infections with a special reference to the effects on tissue gas tensions. AB - Clostridial gas gangrene and perineal necrotizing fasciitis or Fournier's gangrene are rare but serious infections with an acute onset, rapid progression, systemic toxemia and a high mortality rate. The aim of this study was to investigate the efficacy of surgery, antibiotic treatment, surgical intensive care and in particular the role of hyperbaric oxygen (HBO) in the management of these infections. An experimental rat model was used to investigate the possibilities for measuring tissue oxygen and carbon dioxide tensions during hyperbaric oxygen treatment. In addition to this preliminary experimental study, Silastic tube tonometer and capillary sampling techniques were tested to measure the effect of hyperbaric oxygen treatment on subcutaneous oxygen and carbon dioxide tensions in patients with necrotizing fasciitis and healthy controls. Between January 1971 and April 1997, 53 patients with Clostridial gas gangrene were treated in the Department of Surgery, University of Turku. The patients underwent surgical debridement, broad spectrum antibiotic therapy and a series of hyperbaric oxygen treatments at 2.5 atmospheres absolute pressure (ATA). Twelve patients died (22.6%). Hyperbaric oxygen therapy in gas gangrene seems to be life , limb- and tissue saving. Early diagnosis remains essential. Patient survival can be improved if the disease is recognized early and appropriate therapy instituted promptly. Between February 1971 and September 1996, 33 patients with perineal necrotizing fasciitis were treated in the Department of Surgery, University of Turku. The management included surgical debridement of the necrotic tissue with incisions and drainage of the involved areas, antibiotic therapy, hyperbaric oxygen treatment at 2.5 ATA pressure and surgical intensive care. Three patients died giving a mortality rate of 9.1%. The survivors received hyperbaric oxygen therapy for 2-12 times. Our results indicate that hyperbaric oxygenation is an important therapeutic adjunct in the treatment of Fournier's gangrene. Electrical equipment should not be used unsheltered in a hyperbaric chamber due to the increased risk of fire. The subcutaneous tissue gas tensions of rats were therefore measured using a subcutaneously implanted Silastic tube tonometer and a capillary sampling technique. The method was successfully adapted to hyperbaric conditions. The subcutaneous oxygen tension levels increased five fold and the carbon dioxide tension levels two fold compared to initial levels. The PO2 and PCO2 of subcutaneous tissue and arterial blood were measured directly in six patients with necrotizing fasciitis and three healthy volunteers in normobaric conditions and during hyperbaric oxygen exposure at 2.5 ATA pressure. The measurements were carried out in healthy tissue and at the same time in the vicinity of the infected area of the patients. During HBO at 2.5 ATA subcutaneous oxygen tensions increased several fold from baseline values and carbon dioxide tensions also increased, but to a lesser degree in both healthy and infected tissues. When examining the subcutaneous PO2 levels measured from patients with necrotizing fasciitis, the PO2 was regularly higher in the vicinity of the infected area than in healthy tissue. In general, HBO treatment resulted in a marked increase in tissue oxygenation in both healthy tissue and in the vicinity of infected tissue. The hyper-oxygenated tissue zone surrounding the infected area may be of significance in preventing the extension of invading microorganisms. PMID- 11199292 TI - [Bullet injury of the bladder. In the novel "La Regenta" by Leopoldo Alas "Clarin"]. AB - Some great literature works show medical pictures of high historical value. In "La Regenta", by Leopoldo Alas Clarin (1852-1901), considered the best XIX century Spanish novel and one of the most important of the whole Spanish literature, there is a faithful account of a bullet wound of the bladder: the possibility of making the diagnosis, the complications and inevitable poor prognosis are depicted, since in the story the wound is followed by peritonitis and death of the wounded character, with the attending doctors rejecting a transfer to the hospital or a surgical intervention. This episode reminds us of an important chapter in the History of Surgery and Urology: the diagnosis of trauma wounds of the urinary tract, based over a long time on the data provided by urethral catheterisation; and the treatment of penetrating abdominal wounds in general, a matter of discussion between partisans and detractors of surgical exploration, that had a high mortality until well into the XX-century, when modern means of vital support, anaesthesia and antiseptics were on hand. PMID- 11199293 TI - [Effect of the neuropeptides bombesin and calcitonin on the growth of prostate cell lines, PC-3, DU 145, and LNCaP]. AB - Neuroendocrine cells are present in normal and tumoral prostate tissue, the neuropeptides secreted by this cells have a biological functions that have not been fully elucidated. The presence of neuroendocrine cells in prostatic carcinoma have been shown to increase tumor progression. We characterized the in vitro proliferative influence of bombesin and calcitonin in androgen-insensitive, PC-3 and DU-145, and androgen-sensitive, LNCaP, cell lines of human prostate cancers. The influence of these neuropeptides on proliferation were assessed using the colorimetric XTT assay and by cells counts with a hemocytometer. The growth of PC-3 and DU-145 cell lines is stimulated by bombesin and calcitonin but exerted any stimulatory effect on the proliferation of the LNCaP cell line. This indicate that bombesin and calcitonin can modulate proliferation of androgen insensitive human prostate cell lines "in vitro" and may be potential paracrine growth promoters in stablished androgen irresponsive human prostatic carcinoma cells. PMID- 11199294 TI - [DNA ploidy determination with flow cytometry, Ki-67 index, and overexpression of p53 protein in 121 T1 superficial bladder carcinoma. Retrospective study. Correlation with classic variables]. AB - OBJECTIVE: Observe the correlation between Ki-67 label index, p53 expression and flow cytometry-DNA ploidy with the classic variables (grade, lymphatic permeation, multiplicity, volume, primary). MATERIAL AND METHOD: 121 superficial bladder tumors T1. 10% Cut-off level for Ki-67 and p53. Aneuploidy is defined as a tumor with DNA index different of 1 or more than 20% in G2-M phase. RESULTS: Statistical correlation with grade and lymphatic permeation. Ki-67 label index and p53 expression can distinguish between G1, G2 vs G3 and Lx, L0 vs. L1. The volume correlates with positivity to p53. CONCLUSIONS: Aneuploidy and positivity to Ki-67 and p53 increase with grade and lymphatic permeation. PMID- 11199295 TI - [Test with intracavernous injection of PGE1 in erectile dysfunction: our experience]. AB - OBJECTIVES: To evaluate the answer and side-effects after the test of intracavernous injection of prostaglandin E1 in patients with erectile dysfunction. MATERIAL AND METHOD: In the last three years we have carried on 500 tests of intracavernous injection of prostaglandin E1 with the support of infirmary. The purpose was to train the patient and his partner on this technique. RESULTS: The more frequent cause of erectile dysfunction turned to have a vascular origin. In most of the cases, once that the technique has been learnt, the intracavernous injection has been carried on by the patient. The level of acceptance has reached a 85%, with a very low rate of complications. According with our protocol, the learning process has required of a media of 2 or 3 visits where the couple has been trained on this technique and the optim individual dose has been set. CONCLUSION: The intracavernous injection test carried on by an erectile dysfunction unit with the support of an infirmary team reach a high level of acceptance and efficiency. Although new medicine has appeared, we considered the objectification test of the erection with PGE1 very useful, easy-to-use and with low complication rate. It can also be used as a therapeutical option. PMID- 11199296 TI - [Determining factors in the presence of carcinoma in prostate biopsies]. AB - PURPOSE: Prostate biopsy is the diagnostic method to detect prostate carcinoma. We try to identify the optimal PSA cut-off, biopsy indication and the clinico pathological characteristics in order to differentiate those patients with negative biopsy in which we should repeat the proceeding. METHOD: We study 344 biopsies in 292 patients for 16 months. An univariate and multivariate study to identify the influent factors in the existence of prostate cancer in the first biopsy and in the patients with a second one was taken place. RESULTS: Patients in the first biopsy Univariate study: Out of these variables (PSA, PSA ratio, digital rectal examination and prostate volume) just the PSA has statistical significance. Multivariate study: Only the the PSA is an indepent influence factor. Receiving Operated Curve: The optimal cut-off is 10.5 ng/ml. Patients with a second biopsy Univariate study: None of the variables is related with the existence of prostate cancer. Groups comparison: A comparison between the patients in the first biopsy and the patients with a second biopsy is performance with no statistical differences in the variables already mentioned. CONCLUSION: The patient with a PSA greater than 4 ng/ml should be perform a prostate biopsy, mostly if his PSA is over 10 ng/ml. In our experience we do not related the need of a second biopsy with any factor in particular, therefore in our opinion and because of the high rate of negative false, all of the patients should be controlled and undergo a second biopsy if any change in PSA or clinics modification takes place. PMID- 11199297 TI - [Subepithelial hemorrhage of renal pelvis (Antopol-Goldman lesion). Report of 4 cases and review of the literature]. AB - OBJECTIVES: The subepithelial hematoma of renal pelvis (Lesion of Antopol Goldman) is a rare entity that preferably is diagnosed clinically as a neoplasic lesion. METHODS: We present four new cases of subepithelial hematoma of renal pelvis diagnosed in our hospital from 1989. RESULTS: Our cases presented clinically with hematuria and flanc pain, preferably in the left side (3 out of 4). After nephrectomy, all the cases showed a subepithelial hematoma of variable extension that can occupy the renal pelvis and calices, associated to hidronefrosis, cortical infartion, renomegaly or renal angioma. Additionally, two of our patients presented with dilation of the pielocalicial system, and a third one presented with urotelial carcinoma of the ureter, being therefore the lesion of Antopol-Goldman an incidental discovery. In the remaining case, the presence of multiple renal hemangiomas was identified as cause of the renal pelvic hematoma. CONCLUSIONS: The preoperatore diagnosis of the lesion of Antopol Goldman is difficult although it should be included as differential diagnosis in those cases with hematuria and alterations of renal pelvis in the image techniques, because an early diagnosis could imply a conservative treatment with pieloplastia or partial nephrectomy. PMID- 11199299 TI - [Spontaneous extraperitoneal bladder perforation caused by bladder carcinoma]. AB - We show a case of spontaneous extraperitoneal vesical perforation due to presence of a bladder cancer with urotelial origin. PMID- 11199298 TI - [Conservative treatment of germ cell tumor of the testis]. AB - Testis germ cell tumor is the most frequent cancer in men between 15 and 35 years old. The therapeutic results of radical orchiectomy and chemotherapy reaches 90% free disease survival al the present time. This great chemosensibility is opening new doors to alternative therapeutic options, directed to preserve the sufficient amount of tissue to avoid the problems derived from testicular insufficiency. Such alternatives are clearly beneficial in bilateral germinal tumors or in solitary testis. In this article we describe a case of seminoma developed in a solitary functional testis managed in a conservative approach: organ preserving surgery and surveillance. We analyzed the indications and international results of such approach based on the best evidences now available. PMID- 11199300 TI - [Spontaneous autoembolization in a child with high-flow post-traumatic priapism]. AB - There are two sort of priapism: the venous or low flow priapism, that is usually painful, and the arterial or high flow one, painless and rare, especially in childhood. We present a case of a boy 5 years old, who 6 days after to suffer a perineal closed traumatism, had a painless and arterial priapism, with aneurism and fistula of the dorsal penile arteria, that was resolute spontaneously through self-embolization, 11 days after. We review the bibliography of 14 cases of arterial posttraumatic priapism in childhood, without find any case resolute by spontaneous self-embolization. PMID- 11199301 TI - [Ultrasonographic diagnosis of massive bladder hernia at the inguinoscrotal level: report of a case]. AB - We present a case of massive inguinoscrotal bladder hernia in a 58 years-old man with a left inguinal hernia. It was diagnosed by ultrasound during evaluation of a mass in the left inguinal region extending to the scrotum. Cystography later confirmed the ultrasound findings but provided no new information. Although filling cystography is considered to be the gold-standard radiological diagnostic procedure for this entity I the use of ultrasound should not be discarded. Firstly I because direct and indirect ultrasonographics signs characterising inguinal bladder hernias have been reported, and secondly I to help in the differential diagnosis of a scrotal mass. PMID- 11199302 TI - [Cobb's collar. Unusual cause of hematuria]. AB - The Cobb's collar is a congenital narrowing of the bulbar urethra with variable clinical presentation and obstruction grade. Herein we report a clinical case of a 13-year-old boy presenting terminal macroscopic haematuria and post-mictional urethral bleeding. At cystoscopy a membrane on the bulbar urethra distal to the external sphincter and prominent vessels in the prostatic urethra were found. Transurethral endoscopic incision was carried out with no complications or recurrence at 9-month follow-up. The authors briefly review the embryopathogenesis, clinical features and treatment of this uncommon anomaly. PMID- 11199303 TI - [Testicular microlithiasis. Clinical significance and therapeutic implications]. AB - Testicular microlithiasis is a rare condition usually diagnosed by scrotal ultrasound and associated with pathology of the testis. We report two pediatric cases presented with acute scrotum. Testicular sonography revealed significant bilateral testicular microlithiasis. One case was diagnosed as having torsion of the right testis and the other case as orchiepididymitis. A careful review of the literature is made and a periodic follow-up of this disease is advocated. PMID- 11199304 TI - [Massive lymphatic involvement secondary to prostatic adenocarcinoma]. AB - Prostatic carcinoma may be diagnosed by the clinic manifestations or by the symptoms for locoregional disemination and distance metastasis. The lymphatic system is the first metastatic station, which is affected in a high percentage of cases. Event it may simulate lymphoproliferatives process and it si uncommon the lymphatic macroaffectation at first. In theses cases, the histologic and immunohistochemical study by the determination of prostatic specific antigen in lymph nodes can provice the diagnosis. Treatment of these tumors is palliative with hormonotherapy. Prognosis is bad with a low survival at five years. PMID- 11199305 TI - [Trazodone-induced priapism]. AB - We present a 41 years old male, treated with trazodone because of depression. He was seen at our Andrology unit for a 72 hours evolutioned priapism. We review the literature and submit this paper for publication because it is an uncommon pathology. PMID- 11199306 TI - [Fibroepithelial polyp in distal ureter]. PMID- 11199307 TI - Carbon coated polyethylene: effect of surface energetics and topography on human platelet adhesion. AB - The influence of surface energy and structural properties of carbon coated polyethylene (PE) on the human platelet adhesion was studied. Three types of amorphous carbon coating were obtained by plasma pulse discharge, with the number of pulses grading as 10, 50, 100. Human serum albumin adsorption experiments have been carried out with all samples in vitro. Platelet adhesion analysis by SEM included determination of total quantity of adherent platelets, and respective quantities of platelets at different stages of activation (single, spread, aggregates). Surface topographies ranged from bare PE and such (10 pulses), to globular 0.5 microm in size (50 pulses), and complex fibrillar 3-4 microm structures (100 pulses). Surface free energy varies from 31.7 +/- 0.6 to 40.4 +/- 0.6 mN/m for uncoated PE and 10 pulse coatings, respectively, as determined by contact angle techniques. All studied coatings demonstrate weaker platelet activation properties in comparison with untreated PE. Among all studied coatings, the 50 pulse coated surface seems to be the least suitable for contact with platelets, mainly due to its structural rather than to its energy properties. These data are related to a sharp decrease in the adsorbed protein level for the samples with 50 pulse coatings. The applied analysis of platelet activation enables more accurate characterization of platelet-biomaterial interaction. PMID- 11199308 TI - Investigation on the ability of an ultrasound bubble detector to deliver size measurements of gaseous bubbles in fluid lines by using a glass bead model. AB - Detectors based on ultrasonic principles are today's state of the art devices to detect gaseous bubbles that may be present in extracorporeal circuits (ECC) for various reasons. Referring to theoretical considerations and other studies, it also seems possible to use this technology to measure the size of detected bubbles, thus offering the chance to evaluate their potential hazardous effect if introduced into a patient's circulation. Based on these considerations, a commercially available ultrasound bubble detector has been developed by Hatteland Instrumentering, Norway, to deliver bubble size measurements by means of supplementary software. This device consists of an ultrasound sensor that can be clamped onto the ECC tubing, and the necessary electronic equipment to amplify and rectify the received signals. It is supplemented by software that processes these signals and presents them as specific data. On the basis of our knowledge and experience with bubble detection by ultrasound technology, we believe it is particularly difficult to meet all the requirements for size measurements, especially if these are to be achieved by using a mathematical procedure rather than exact devices. Therefore, we tried to evaluate the quality of the offered bubble detector in measuring bubble sizes. After establishing a standardized test stand, including a roller pump and a temperature sensor, we performed several sets of experiments using the manufacturers software and a program specifically designed at our department for this purpose. The first set revealed that the manufacturer's recommended calibration material did not meet essential requirements as established by other authors. Having solved that problem, we could actually demonstrate that the ultrasonic field, as generated by the bubble detector, has been correctly calculated by the manufacturer. Simply, it is a field having the strongest reflecting region in the center, subsequently losing strength toward the ECC tubing's edge. The following set of experiments revealed that the supplementary software not only does not compensate for the ultrasonic field's inhomogeneity, but, furthermore, delivers results that are inappropriate to the applied calibration material. In the last set of experiments, we were able to demonstrate that the signals as recorded by the bubble detector heavily depend upon the circulating fluid's temperature, a fact that the manufacturer does not address. Therefore, it seems impossible to resolve all these sensor related problems by ever-increasing mathematical intervention. We believe it is more appropriate to develop a new kind of ultrasound device, free of these shortcomings. This seems to be particularly useful, because the problem of determining the size of gaseous bubbles in ECC is not yet solved. PMID- 11199309 TI - The LPD-II: a modified locked percutaneous device that permits safe subcutaneous access. AB - A locked percutaneous device, the LPD-I (previously described as LPD), is effective in overcoming the problems of skin downgrowth and local tissue infection; however, it can only be implanted at a site providing adequate subcutaneous adipose tissue to attach to the subcutaneous connector of the LPD-I. A modified device, the LPD-II, has been developed that has a thin dome and skin connector but does not have a subcutaneous tissue connector. In addition, a newly designed structure called the skin stop collar (SSC) has been developed. It is positioned just beneath the mesh collar described in the LPD-I to further improve the function of the LPD-II. Six rabbits were implanted with one LPD-II without the SSC (group 1) and five rabbits were implanted with one LPD-II with the SSC (group 2). For more than 6 months, two of the implants in group 1 rabbits were successful. Four of the implants in group 2 rabbits were successful for more than 1 year. One of the animals in group 2 died of causes unrelated to the device. We conclude the following: the mesh collar skin connector can function well as a locked percutaneous device without the subcutaneous tissue connector; the LPD-II can be implanted in any site and does not require the presence of subcutaneous adipose tissue; and the SSC may increase the success rate of LPD-II implantation provided the mesh collar is made of soft material. PMID- 11199310 TI - Altruism and the volunteer: psychological benefits from participating as a research subject. AB - Psychiatric assessment of potential volunteers for hazardous biomedical experimentation should include an assessment of the motivations underlying the altruistic action of volunteering. Screening goals include evaluation of informed consent as well as screening out experimental subjects who would be likely to be psychologically harmed by participation. This discussion of psychological issues to be considered, beyond those of informed consent and screening for severe psychopathology, originated in the psychiatric screening of the small group of original volunteers for the "Dobelle eye" Artificial Vision Project. These individuals entered the project over 20 years ago at a time when they could expect no tangible benefit from participation. Superficially altruistic behavior, such as volunteering for this project, serves multiple psychological functions and in a given clinical case, the determinants are often complex. A spectrum of altruistic behavior is suggested, based on interviews with these original subjects as well as from extensive evaluation of patients studied in the setting of psychoanalytic treatment with one of the authors (B.J.S.). We suggest that adaptive altruism can explain the finding that some volunteers gained actual psychological benefit from their participation. This unanticipated finding, that participating in research as an experimental subject can result in lasting improvement in self-esteem, is discussed. Suggestions are made for increasing the likelihood of such benefit. Ethical ramifications are addressed. PMID- 11199311 TI - Survival of prosthetic grafts of different materials after impairment of a native arteriovenous fistula in hemodialysis patients. AB - In our department, hemodialysis vascular accesses with graft, are used in patients with impairment of native distal and proximal arteriovenous fistulas (AVF-E). The aim of this study was to compare the survival of grafts of different materials (PTFE vs. bovine vein) in these patients. From 1991 to 1999, we prospectively evaluated 53 patients (35 women, 18 men, age 68 +/- 11 years, on dialysis for 70 +/- 65 months). Fifty-three PTFE, 10 reinforced PTFE, and 22 bovine vein grafts were placed. We evaluated the primary patency (PP) (days between fistula placement and the last dialysis before thrombosis occurred) and the secondary patency (SP) (days between fistula placement and the last dialysis treatment before it was considered lost) by separating PTFE survival from that of bovine veins. In the same patients, we also evaluated the survival of the native arteriovenous fistulas (AVF-E) during the pregraft period. Furthermore, we evaluated 404 patients (172 women, 232 men, age 65 +/- 14 years, on dialysis for 50 +/- 53 months) in whom only AVF-E were placed during the same follow-up period. Graft and AVF-E survival were calculated according to the Kaplan-Meier method. In patients with grafts, the PP at 1 year was 17.4% for PTFE and 23.9% for bovine veins. At 12 months, the SP of bovine veins was significantly higher than that of PTFE (81,9% vs. 50%, p < 0.04). In the patients who only had AVF-E, the PP and SP was, respectively, 43% at 12 months and 52.4% at 50 months. A preliminary experience in 22 patients with a 20 month follow-up confirms better survival of bovine veins than PTFE (p < 0.04). PMID- 11199312 TI - Anatomic study of the pulmonary artery as a conduit for an artificial lung. AB - Our group is developing an artificial lung as a bridge to transplant. We evaluated the sheep pulmonary artery (PA) for the presence or absence of a septum, which may increase PA resistance and affect artificial lung flow. We also measured the PA size to determine whether it is a suitable conduit for artificial lung implantation using a PA-PA shunt. Adult Suffolk ewes in two groups were studied. Group 1 consisted of animals (n = 12, 30-43 kg) prepared for thoracotomy. Group 2 (n = 21, 30-43 kg) consisted of postmortem dissections. In both groups, the length and girth of the PA was measured. The heart and lungs were removed on all postmortem animals (group 2), the ductus arteriosum was crosscut, and the common PA was incised. The average length of the PA in live animals was 5.5 cm and the average diameter was 2.2 cm. The average length of the PA in postmortem animals was 4.8 cm and the average diameter was 2.0 cm. All pulmonary arteries were aseptate, and the ligamentum arteriosum in each PA was not patent. We conclude that the PA is not a source of increased resistance and is a suitable conduit for artificial lung implantation in the PA-PA configuration. PMID- 11199314 TI - Perfusion with lipopolysaccharide negative blood eliminates lipopolysaccharide induced lung injury. AB - We investigated whether perfusion with control blood improves pulmonary functions compromised by lipopolysaccharide (LPS) infusion. This was an animal study in a research laboratory at a university hospital by using Sprague-Dawley rats (n = 19), each weighing 325 to 350 g. All animals were pretreated with a 24 hour infusion of either LPS (5 mg/kg) or vehicle, after which, excised lungs were reperfused for 2 hours with either LPS+ or control blood. Three groups were studied: (1) group S (n = 6); LPS pretreated lungs reperfused with LPS containing blood to mimic persistent sepsis, (2) group N (n = 6); LPS pretreated lungs reperfused with control blood to mimic the removal of the septic blood components, and (3) group C (n = 7); vehicle pretreated lungs reperfused with normal blood as a control. Blood gas exchange, shunt fraction (Qs/Qt), alveolar arterial oxygen gradient (A-aDO2), and variables for lung mechanics were measured. Leukosequestration was quantified with a myeloperoxidase (MPO) assay. The PO2 (mm Hg) values at 90 min after reperfusion in groups S, N, and C were 67.8 +/- 7.0*, 85.2 +/- 9.2, and 90.1 +/- 7.5, respectively (*p < 0.05; vs. group N and C). In addition to PO2, A-aDO2 and Qs/Qt significantly deteriorated in group S. MPO activity in the lungs after LPS infusion was significantly higher than that after vehicle infusion (1.7 +/- 0.3 vs. 0.12 +/- 0.04 units/g tissue; p < 0.001). Subsequent reperfusion with LPS+ blood (group S) increased MPO activity to 3.1 +/- 0.6 (p < 0.05), but reperfusion with normal blood (group N) caused a significant decrease to 1.1 +/- 0.2 (p < 0.05). MPO activity in group C did not significantly change compared with those after vehicle infusion. Reperfusion with control blood normalized lung function compromised by pretreatment with LPS and significantly reduced leukosequestration. These results favor the possibility that the removal of LPS+ blood components may eliminate septic lung injury. PMID- 11199313 TI - Comparison of three commercially available hollow fiber oxygenators: gas transfer performance and biocompatibility. AB - The new generation of oxygenators have improved blood flow pathways that enable reduction in priming volume and, thus, hemodilution during cardiopulmonary bypass (CPB). We evaluated three oxygenators and two sizes of venous reservoirs in relation to priming volume, gas transfer, and blood activation. To compare priming volume, gas transfer, and biocompatibility of three hollow fiber oxygenators and two different size venous reservoirs, 60 patients were randomly allocated in groups to undergo cardiopulmonary bypass. In each group, an oxygenator with a different surface area and priming volume was used: 1.8 m2 and 220 ml (group 1, n = 23), 2.2 m2 and 290 ml (group 2, n = 20), and 2.5 m2 and 270 ml (group 3, n = 17). In groups 1 and 3, a large soft shell (1900 ml) venous reservoir was used, whereas in group 2, a smaller soft shell (600 ml) venous reservoir was used. Gas transfer was assessed by calculating the oxygen transfer rate for each group and per square meter for each oxygenator group. Partial arterial oxygen pressure (paO2) and partial arterial carbon dioxide pressure (paCO2) between the groups were assessed with forward stepwise regression analysis. Biocompatibility was evaluated through measurement of platelet numbers, complement activation products (C3b/c), coagulation (thrombin anti-thrombin III complex), and fibrinolysis (plasmin anti-plasmin complex). No differences were found in oxygen transfer rate per group. However, when correcting the oxygen transfer rate for surface area, group 1 demonstrated a higher oxygen transfer rate compared with group 2 (p < 0.05) at an FiO2 of 40 and 60% and compared with group 3 at an FiO2 of 60 and 70%. The regression analysis showed that the average arterial PO2 was the highest in group 3, i.e., 79.2 mm Hg higher than in group 1 (p < 0.001) and 73.5 mm Hg higher than in group 2 (p < 0.001). Group 3 also had the lowest average arterial pCO2, 0.57 mm Hg lower than in group 1 (p = 0.004) and 0.81 mm Hg lower than in group 2 (p < 0.001). During CPB, platelet numbers decreased significantly in all groups (p < 0.001), without differences between the groups. C3b/c levels increased in all groups during CPB. At cessation of CPB the C3b/c level in group 2 (398 nmol/L(-1)) was significantly higher compared to group 1(251 nmol/L(-1); p < 0.05) and group 3 (303 nmol/L(-1); p < 0.05). Thrombin anti-thrombin III complexes and plasmin anti-plasmin complex complexes increased during CPB to significantly high levels at cessation of CPB, but there were no differences between the groups. The oxygenator with the smallest surface area and lowest priming volume (group 1) had the highest oxygen transfer rate per square meter and showed the least blood damage, as depicted by complement activation. The oxygenator with the largest blood contact surface area and improved geometric configuration (group 3) showed the lowest oxygen transfer rate per square meter. However, this oxygenator elevated oxygen partial pressure the most and reduced carbon dioxide partial pressure the most. In group 2, where a smaller venous reservoir was used, the highest blood activation was observed. PMID- 11199315 TI - LD-PACE II: a new cardiomyostimulator for cardiac bioassist. AB - The LD-PACE II was designed for use in cardiomyoplasty, aortomyoplasty, and skeletal muscle ventricles. All parameters specified as programmable can be changed in a noninvasive manner (using a programming interface wand connected to a computer using the Windows 95/98 environment). Two new functions may be very useful clinically, based on experimental research. 1. Work-rest regimen. The LD PACE II is able to deliver alternating periods of muscle contractions and rest. Work and rest periods may be programmed independently between 1 and 120 minutes in increments of 1 minute. The work-rest regimen may be useful clinically if muscle contractions are needed for cardiac assist postoperatively. 2. Night/day regimen. This feature allows for a change in the ratio of muscle contractions according to a patient's activity level. During the day the cardiosynchronization ratio may be set from 1:1 to 1:4, and during the night it may be set for 1:8 to 1:16. This allows the muscle to have a long rest period, prevents overuse, and prolongs battery life. These two new features make this cardiomyostimulator very attractive for cardiomyoplasty in particular. The addition of the work-rest and night-day regimens allow the muscle to rest for periods during the day to prevent overuse, subsequent damage, and potential atrophy. PMID- 11199316 TI - Optimized veno-venous bypass with the affinity pump. AB - Veno-venous bypass (VVBP) is increasingly used to avoid acute venous hypertension and low cardiac output after clamping the vena cava. Air embolism upon accidental decannulation of the inflow line and endothelial damage due to suction of the blood collecting cannula to the vessel wall are known complications specific to the currently used roller and centrifugal pumps, because they generate negative pressure at the inflow site of the pump. The Affinity pump has a unique chamber design with an occlusive segment, that collapses in low filling states preventing negative pressure at the inflow site of the pump chamber. This device was tested for VVBP in three pigs (each weighing 52.3 +/- 5.1 kg) with hepatic vascular exclusion. Blood was pumped from the femoral and portal veins to the external jugular vein and perfusion was maintained for 6 hours. The hemodynamic state of the animals was assessed by recording heart rate; systolic, mean arterial, and diastolic pressure; as well as central venous pressure. Mean pump flow during the experiment was 1,629.3 +/- 372.2 ml/min. After clamping, the inflow line of the pump mean arterial pressure significantly decreased (from 69.5 +/- 4.4 to 43.1 +/ 3.5 mm Hg), and mean pressure in the femoral vein increased significantly (from 16.1 +/- 2.6 to 26.8 +/- 5.9 mm Hg), whereas the mean pressure in the internal jugular vein did not significantly change (from 6.0 +/- 1.7 to 5.0 +/- 2.1 mm Hg). There was no suction by the blood collecting cannula on the vessel wall, and neither bubbles nor air emboli were detected and no operator intervention was needed. In conclusion, the Affinity pump eliminates device related complications due to negative pressure generated at the inlet, and guarantees stable hemodynamics. Its application is simple and safe and minimal operator intervention is needed, making the Affinity pump particularly suited for veno venous bypass. PMID- 11199317 TI - Impact of United States artificial organ development in Latin America. AB - The University of Minnesota may be considered the cradle of heart surgery worldwide. That is where Dr. F. John Lewis carried out the first open heart surgery in September, 1952 and repaired an atrial septal defect in a 5 year old girl. Thenceforth, new solutions to allow systematic heart surgeries have been extensively investigated. This requires boldness and imagination. In 1954, Dr. Walton Lillehei, who had been working in Minnesota since after the war, carried out the first surgery with cross circulation using a second person who worked as a circulatory support, while the patient's heart was operated on. In 1955, he started using extracorporeal circulation using an oxygenator developed in association with Dr. Richard de Wall and the roller pump introduced by Michael DeBakey. By 1956 they had already performed 80 surgeries using the bubble oxygenator. PMID- 11199318 TI - Effects of prosthetic valve placement on mitral annular dynamics and the left ventricular base. AB - Insertion of a rigid mitral prosthesis impairs the function of the mitral annulus and induces systolic narrowing of the left ventricular outflow tract (LVOT). To study this mechanism, we investigated dynamic changes in the left ventricular (LV) base, which consists of the mitral annulus and LVOT orifice. In seven patients with mechanical mitral valve prostheses and eight normal subjects, the image of the LV base was reconstructed three-dimensionally and its dynamic change during systole was studied. In the patients, the rigid prosthetic valve (=mitral annulus) tilted toward the left ventricle with a hinge point at the posterior mitral annulus during systole. The left ventricular base exhibited contraction, but the size of the prosthetic valve was constant. As a consequence, the prosthetic valve occupied more of the left ventricular base, which resulted in narrowing of the LVOT. In the normal subjects, the mitral annulus did not interfere with the region of the LVOT orifice during systole as the mitral annulus underwent both dorsiflexion and contraction. Thus, fixation of the mitral annulus induces an anti-physiologic motion of the annulus. Conscious preservation of annular flexibility in mitral valve surgery is important in avoiding potential dynamic LVOT obstruction. PMID- 11199319 TI - Evaluation of a novel vitamin E coated cellulosic membrane hollow fiber dialyzer. AB - Adverse physiologic effects accompany hemodialysis. Biocompatible dialyzer membranes may both limit oxidative stress and decrease beta2-microglobulin production, thereby reducing patient morbidity. We compared standard solute clearance, lipid, and antioxidant effects of a novel cellulosic membrane dialyzer modified with covalently bonded vitamin E (Excebrane Clirans E15, Terumo Australia) with standard cellulosic and polysulphone membrane dialyzers. Stable adult hemodialysis patients taking no lipid lowering or antioxidant therapy (n = 17; 9 male, 8 female) were recruited into a 10 week, prospective, unblinded study. Measurements were made at baseline on their usual dialyzer and after 2, 4, and 10 weeks of Excebrane use. Excebrane demonstrated good in vivo clearance of standard solutes relative to surface area. Predialysis beta2-microglobulin levels were unchanged with time and were significantly lower postdialysis than with cellulose acetate (p < 0.05). Oxidized low density lipoprotein levels as measured by nitrotyrosine residues were high predialysis, but tended to decrease with both membranes (p > 0.05). Total antioxidant status fell during dialysis (p < 0.0005), but plasma vitamin A and E concentrations increased (p = 0.007 and p = 0.02, respectively). Baseline vitamin A levels were high in all patients and, along with vitamin E, total antioxidant status and lipid profiles did not change over time with Excebrane use. Excebrane is an efficient, biocompatible membrane with no deleterious effects on beta2-microglobulin or lipids. More long-term study is merited. PMID- 11199320 TI - Risk factor paradox in hemodialysis: better nutrition as a partial explanation. AB - The higher mortality rate in patients on hemodialysis is primarily due to the higher rate of cardiovascular disease. Yet, paradoxically, overweight, hypertension, and hyperlipidemia, which are cardiovascular risk factors in the general population, have been reported to correlate with better patient survival in hemodialysis. To examine whether this "risk factor paradox" in hemodialysis is due to the positive influence of accompanying better nutrition, we prospectively obtained data on fasting lipids, biochemical markers of nutrition, body mass index (BMI), and blood pressure (BP) in 453 hemodialysis patients and related them to 1 year mortality. As previously noted, body weight, blood pressure, and certain serum lipids positively correlated with survival. Serum prealbumin, one of the most sensitive and specific biochemical markers for nutrition, correlated positively with hypercholesterolemia (r = 0.30, p < 0.001) and BMI (r = 0.12, p < 0.02), but not with mean arterial pressure (MAP) (r = 0.01, p = NS). By analysis of variance, patients in the upper tertile (i.e., higher levels) of BMI and cholesterol but not MAP had significantly higher serum prealbumin and creatinine compared with those in the lower tertile. Our data lend support to the hypothesis that, in patients on hemodialysis, the positive effect of higher BMI and hyperlipidemia but not of high BP could be partially explained on the basis of the accompanying better nutrition. Although not proven, correcting risk factors while improving nutrition may offer better outcomes for patients on dialysis. PMID- 11199321 TI - Predictors of erythropoietin responsiveness in chronic hemodialysis patients. AB - The impact of dialysis intensity on erythropoietin (EPO) requirements is unclear. Previous work suggests that increased dialysis is associated with increased erythropoietin responsiveness (ERSP), but average dialysis intensity has increased since those publications. We hypothesized that ERSP would be independent of delivered Kt/V(urea) at current intensities of hemodialysis. We prospectively studied 135 stable chronic hemodialysis patients who receive iron and subcutaneous EPO dosed according to current guidelines. We collected biochemical, hematologic, and single pool urea kinetics data. ERSP was expressed as units per kilogram per week of EPO administered. Simple and multiple linear regression were used to identify characteristics predictive of ERSP. The mean age of the patients was 62 +/- 17 years (range, 17-90 years); 68 of 135 (50.3%) were women, and 120 of 135 (88.9%) were Caucasian. Mean delivered Kt/V(urea) was 1.60 +/- 0.49, with 102 of 135 (75.6%) of patients with a delivered Kt/V(urea) > 1.3. Univariate linear regression showed seven significant independent predictors of erythropoietin requirements. Low serum albumin (p < 0.001), low serum calcium (p = 0.002), high serum phosphate (p = 0.004), and high serum iPTH (p = 0.007) were all associated with lower levels of ERSP. Lower ERSP was also correlated with lower hemoglobin and lower serum iron and transferrin saturation. Delivered dialysis (Kt/ V(urea)) was not a significant predictor of ERSP (p = 0.61). Multivariate regression confirmed low serum albumin (p < 0.01), high serum phosphate (p = 0.001), high immunoreactive parathyroid hormone (p = 0.025), and low transferrin saturation (p < 0.0005) as predictors of low ERSP, and also found high serum ferritin to be correlated with low ERSP (p = 0.016). We found no relationship between erythropoietin responsiveness and intensity of hemodialysis in this population of patients with a mean delivered Kt/V(urea) of 1.6. This may indicate a threshold effect beyond which more dialysis will not improve ERSP. However, markers of an underlying inflammatory state and of secondary hyperparathyroidism were associated with decreased response to erythropoietin. PMID- 11199322 TI - Predictors of mortality in patients treated with continuous hemodiafiltration for acute renal failure in an intensive care setting. AB - We performed this study to identify predictors of mortality in critically ill patients treated with continuous venovenous hemodiafiltration (CVVHDF) for acute renal failure in an intensive care setting. It was an uncontrolled, observational study that took place in a general intensive care unit in a university hospital. Forty-one patients undergoing CVVHDF for acute renal failure in a consecutive sample of 1,018 ICU treatments were studied. The underlying disease included 25 postsurgical cases and 16 medical cases. Between survivors (n = 23) and nonsurvivors (n = 18), the following factors were assessed: demographic data; the number and type of failed organs; Acute Physiology and Chronic Health Evaluation (APACHE) II scores; urine production; pH; base excess; serum creatinine levels; bilirubin levels; lactate levels; platelet counts; and hemodynamic variables, including cardiac index and central venous pressure. On univariate analyses, the number of failed organs (p < 0.01), presence of hepatic failure (p < 0.01), APACHE II scores (p < 0.01), pH (p < 0.01), base excess (p < 0.001), average urinary production before the initiation of CVVHDF (p < 0.05), and serum bilirubin (p < 0.01) and lactate levels (p < 0.001) were significantly different. Multiple regression analysis identified serum bilirubin (p < 0.01) and lactate levels (p < 0.01) as the predictors of hospital mortality. Presence of hepatic failure was also predictive of hospital mortality (p < 0.01) in the analysis of the type of organ failure. The cut-off value set at bilirubin levels > 10 mg/dl or arterial lactate levels > 3.5 mmol/L provided 83.3% sensitivity and 90.9% specificity in the prediction of hospital death. The crucial factors in predicting outcome of critically ill patients undergoing CVVHDF for renal failure are elevated serum bilirubin and lactate levels at the onset of CVVHDF. Presence of hepatic failure, defined as both jaundice and coagulopathy, may also worsen outcome of critically ill patients undergoing CVVHDF for renal failure. The cut off value set at bilirubin levels > 10 mg/dl or arterial lactate levels > 3.5 mmol/L may serve as beneficial predictors of hospital mortality. PMID- 11199323 TI - Moment in History. In the beginning. AB - The purpose of this editorial is to give the reader a picture of the earliest days in the delivery of chronic dialysis. It is viewed by a psychiatrist who was asked to help evaluate patients in one of the first hemodialysis centers, not only in the United States, but in the world. PMID- 11199324 TI - Influence of design of the hemodialyzer inlet chamber on red blood cell damage during hemodialysis. AB - Red blood cell damage occurring in the inlet chamber of a hollow fiber dialyzer was investigated by using a simplified model assembly. To vary the geometry of the inlet chamber, four parameters were used in this study, including the entrance angle, the chamber length, the convergence ratio, and the number of holes. The degree of red blood cell damage was represented by the hemolysis ratio. The results show that the hemolysis ratio was affected mostly by the chamber length and the convergence ratio, and less affected by the entrance angle and number of holes. The hemolysis ratio was the lowest when the chamber length was 2 mm and the entrance angle was 15 degrees. In addition, the hemolysis ratio decreased with the convergence ratio. Because the hemolysis ratio was only slightly affected by the number of holes and the flow channel length, the experimental results of this simplified assembly can be used to improve the design of an actual inlet chamber. PMID- 11199325 TI - Resource utilization for peritoneal catheter placement. AB - We reviewed hospitalization data for our large regional peritoneal dialysis (PD) program between January 1, 1997, and November 30, 1998, to determine the impact of inpatient PD catheter placement, by using Toronto Western II catheters placed under general anesthesia. Of 106 catheter placements, 80 were elective in previously identified renal failure patients. In elective cases, mean length of hospital stay was 6.75 days (SD, 7.01), median 4.5 days. These Canadian data are similar to those from the American Health Cost and Utilization Project. Evidently surgical PD catheter placement even in elective, planned circumstances involves a significant use of hospital resources. Current published reports do not outline hospital resource requirements or complication rates for this method. PMID- 11199326 TI - Genetic inferences to elucidate inflammation in atherosclerosis. PMID- 11199327 TI - Physiological consequences of tropomyosin mutations associated with cardiac and skeletal myopathies. AB - Mutations have been identified in alpha-tropomyosin (Tm), a key regulatory protein in striated muscle cells, that are associated with a human cardiac myopathy, hypertrophic cardiomyopathy (FHC) and a human skeletal myopathy, nemaline myopathy (NM). In this review, we highlight experiments aimed at identifying the underlying mechanisms by which mutations in alpha-Tm cause inherited diseases of cardiac and skeletal muscle. Gene transfer of normal and mutant alpha-Tm to isolated adult cardiac myocytes was used to study the primary effects of mutant alpha-Tm proteins on the structure and contractile function of fully differentiated striated muscle cells. Both FHC and NM mutant alpha-Tm proteins incorporated normally into the adult muscle sarcomere, similar to normal Tm but exerted differential "dominant-negative" effects on the contractile function of the muscle cell. FHC mutant alpha-Tm proteins produced hypersensitivity of Ca2+-activated force production with a hierarchy that was related to the clinical severity of each mutation. Conversely, the NM mutant alpha-Tm produced a hyposensitivity of Ca2+-activated force production that may underlie, at least in part, the muscle weakness observed in NM. Taken together, the results suggest that the differential changes in the ability of the mutant Tm proteins to regulate muscle contraction in response to changing Ca2+ concentrations underlie the differential clinical presentation of the cardiac and skeletal muscle myopathies associated with mutations in alpha-Tm. PMID- 11199328 TI - Serum levels of leptin and proinflammatory cytokines in patients with advanced stage cancer at different sites. AB - Leptin is a recently identified hormone produced by the adipocyte ob gene which acts as a negative feedback signal critical to the normal control of food intake and body weight. A number of proinflammatory cytokines, such as interleukin (IL) 1alpha, IL-6, tumor necrosis factor (TNF) alpha and interferon (IFN) gamma, have been proposed as mediators of cancer cachexia. These data suggest that abnormalities in leptin production/release or in its feedback mechanism play a role in cancer patients. To elucidate this we studied the relationship between total serum leptin and serum cytokines IL-1alpha, IL-6, TNFalpha as well as the production of leptin and cytokines by peripheral blood mononuclear cells (PBMC) isolated from cancer patients. Sixteen advanced cancer patients (mainly stage IV) with tumors at different sites were included in the study. The serum levels of leptin in cancer patients were significantly lower than those of healthy individuals at all times (7 a.m., noon, 3 p.m.). No significant differences were found in circadian rhythm between patients and controls. Serum levels of IL 1alpha, IL-6, and TNFalpha were significantly higher in cancer patients than in healthy individuals. An inverse correlation between serum levels of leptin and IL 6 was found in cancer patients. The production in culture of leptin by unstimulated PBMCs and those stimulated by phytohemagglutinin M or by phorbol myristate acetate isolated from cancer patients was very low; no differences were observed in comparison with leptin production by PBMCs from healthy individuals. PMID- 11199329 TI - A prospective study of genetic markers of susceptibility to infection and inflammation, and the severity, progression, and regression of coronary atherosclerosis and its response to therapy. AB - Inflammation plays a key role in susceptibility to coronary atherosclerosis and response to therapy. A diverse array of factors modulates inflammation, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and CD14 receptors on the surface of macrophages. Genes encoding for inflammatory markers have variants that regulate their expression and are potential risk factors for atherosclerosis. We prospectively analyzed the possible association of CD14 260C/T, TNF-alpha -308G/A, and IL-6 -174G/C variants, located in the promoter regions, with the severity, progression, and response to therapy of coronary atherosclerosis in a well-characterized cohort. We studied 375 subjects enrolled in the Lipoprotein and Coronary Atherosclerosis Study (LCAS). Genotypes were determined by polymerase chain reaction (PCR) and restriction mapping. Fasting plasma lipids and quantitative coronary angiograms were obtained at baseline and 2.5 years following randomization to fluvastatin or placebo. Distributions of genotypes were--for CD14: 100 CC, 184 CT, and 86 TT; IL-6: 152 GG, 153 GC, and 62 CC; and TNF-alpha: 244 GG, 110 GA, and 17 AA. The CD14 CC genotype was associated with incidence of new coronary occlusion (P=0.026); TNF-alpha AA genotype with history of myocardial infarction (MI, P=0.04), and A allele with total occlusions at baseline (P=0.027), and systolic blood pressure (P=0.046); and IL-6-174 CC genotype with baseline minimum lumen diameter (P=0.043) and reduction in lipoprotein(a) with fluvastatin (P=0.03). Otherwise, no association between the genotypes and the biochemical, angiographic, and clinical phenotypes was detected, and neither were genotype-treatment interactions. Functional variants of CD14 -260C/T, TNF-alpha -308G/A, and IL-6 -174G/C, implicated in the susceptibility to infection, are unlikely to confer major risk for susceptibility to coronary atherosclerosis and its progression or response to therapy in the LCAS population. PMID- 11199330 TI - Elevated p21 mRNA level in skeletal muscle of DMD patients and mdx mice indicates either an exhausted satellite cell pool or a higher p21 expression in dystrophin deficient cells per se. AB - Abnormalities in proliferation and differentiation of the dystrophin-deficient muscle are a controversial aspect of the pathogenesis of Duchenne muscular dystrophy (DMD). Analyses of molecules involved in cell cycle modulation do not exist in this context. Cells withdrawn from the cell cycle permanently express p21. The fact that p2 1, in contrast to other cell cycle proteins, is not diminished when myotubes are reexposed to growth media, allocates this cyclin dependent kinase inhibitor a special function. Here we report for the first time statistically increased p21 mRNA levels in dystrophin-deficient muscle tissue. Only 42% of conventional RT-PCRs from six muscle samples of human controls yielded positive results but almost all skeletal muscle biopsy samples (87%) from DMD patients (n=5). For p21 mRNA quantification in murine muscle samples we were able to use the exact real-time TaqMan PCR method due to generally higher p21 mRNA levels than in human muscles. In addition, contamination with fibroblasts can be excluded for the murine samples because they do not demonstrate fibrosis at the age of 350 days but start to lose their regenerative capacity. In accord with the results in humans, we observed p21 mRNA levels in mdx mice that were approx. four times as high as those in control mice. Elevated p21 mRNA level may indicate a shift in cell composition towards differentiated p21 expressing cells as a result of an exhausted pool of undifferentiated, non-p21-expressing satellite cells due to previous cycles of de- and regeneration. Alternatively, dystrophin-deficient cells per se may express higher p21 levels for unknown reasons. Although we cannot distinguish between these possibilities, the eventual transfec tion of a patient's own satellite cells with p21 antisense oligonucleotides may enable the dystrophic process to be influenced. PMID- 11199331 TI - Vitamin D receptor gene polymorphism is associated with serum total and ionized calcium concentration. AB - Restriction fragment length polymorphisms of the vitamin D receptor gene have recently been reported to be associated with changes in bone mineral density. Alterations in systemic calcium balance and Ca-regulating hormones such as 1,25(OH)2 vitamin D3 and parathyroid hormone have been demonstrated in essential hypertension. We investigated the relationship between polymorphisms of the vitamin D receptor gene and systemic Ca metabolism in patients with essential hypertension and in normotensives. We compared 147 subjects with essential hypertension and 100 normotensive control subjects. The genotype distribution and derived allele frequencies for the vitamin D receptor gene were similar in the two groups (genotype bb/Bb/BB and allele B/b: 60.1/32.6/7.2 and 0.24/0.76 in hypertensives vs. 56.0/36.0/8.0 and 0.26/0.74 in normotensive subjects). Serum concentrations of total Ca in the bb, Bb, and BB groups were, respectively, 4.5+/ 0.3 vs. 4.5+/-0.4 vs. 4.4+/-0.5 mmol/l in normotensives and 4.6+/-0.3 vs. 4.6+/ 0.4 vs. 4.4+/-0.5 mmol/l in hypertensives. Ionized Ca levels were 1.17+/-0.04 vs. 1.16+/-0.04 vs. 1.15+/-0.04 mmol/l in normotensives and 1.16+/-0.04 vs. 1.16+/ 0.04 vs. 1.14+/-0.05 mmol/l in hypertensives, respectively. These results indicate that the BB genotype of the vitamin D receptor gene is associated with lower serum Ca levels but is not a useful predictive marker for the development of essential hypertension in Japanese subjects. PMID- 11199332 TI - Enhanced detection of mutations in BRCA1 exon 11 using restriction endonuclease fingerprinting-single-strand conformation polymorphism. AB - A novel approach to mutation screening in the large exon 11 (comprising 3427 bp) of the human BRCA1 gene is presented. Restriction endonuclease fingerprinting single-strand conformation polymorphism (REF-SSCP) is based on repeated detection of DNA sequence variants in different restriction endonuclease fragments, and we evaluated the method using blood samples from 25 Norwegian patients with hereditary breast/ovarian cancer. We compared REF-SSCP to constant denaturant gel electrophoresis (CDGE) and to the protein truncation test (PTT). REF-SSCP detected 12 different DNA variants. Four of these were not detected by CDGE, and only one variant detected by CDGE was missed by REF-SSCP. PTT detected 4 of these 13 variants. REF-SSCP was subsequently applied to a second patient series (Swedish, n=20). A total of 14 different DNA variants were detected by REF-SSCP, 6 of which were truncating mutations (PTT detected only 4). Nonsense and frameshift mutations that are putative breast/ovarian cancer mutations, were detected in 7 of the 25 Norwegian and 9 of the 20 Swedish patients. PMID- 11199333 TI - A naturalistic observation of children drawing: peer collaboration processes and influences in children's art. PMID- 11199334 TI - The development of individual styles in children's drawing. PMID- 11199335 TI - The artistic evolution of mommy: a longitudinal case study of symbolic and social processes. PMID- 11199336 TI - Continuity of styles in the drawings of adolescent girls. PMID- 11199337 TI - Looking for the development of artistic style in children's artworlds. PMID- 11199338 TI - Uptake of prolactin and tyroliberin by the heart. AB - The aim of this study was to observe the specificity of prolactin and tyroliberin uptake and thus to determine their affinity for the heart ventricles and atria. Comparison of the uptake of the examined substances revealed that more of these hormones reached the atria than the ventricles. The contents of prolactin and tyroliberin in the atria were statistically significant compared with 125J. The results observed provide evidence for nonuniform prolactin uptake by the heart. PMID- 11199339 TI - Production of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha by a rat corneal epithelial cell line. AB - Production of interleukin (IL)-1 beta, IL-6 and tumor necrosis factor (TNF)-alpha by rat corneal epithelial cells in response to lipopolysaccharide and phorbol-12 myristate-13-acetate (PMA) was tested. Supernatants from rat corneal epithelial cells treated with lipopolysaccharide and PMA were collected after 6, 24 and 48 h and tested with enzyme-linked immunosorbent assay for IL-1 beta, IL-6 and TNF alpha. The activity of TNF-alpha was additionally confirmed with bioassay on L929 cells. It was found that control groups did not produce significant levels of either cytokine. However, after stimulation with lipopolysaccharide, cells produced mainly IL-6, whereas after PMA they produced mainly TNF-alpha. IL-6 levels 24 and 48 h after PMA stimulation were also elevated, which could have been caused by the presence of TNF-alpha. Production of IL-1 beta in all groups was very low and remained within the test sensitivity range. These results show that the rat corneal epithelial cell line produces inflammatory cytokines in response to proinflammatory mediators. For this reason, it could be used for measuring the effects of irritants on the cornea. PMID- 11199340 TI - Disodium clodronate in painful nonresponsive periarthropathy of the hip. AB - This article identifies and describes a small group of patients with trochanteric tendinitis and bursitis in whom all modes of traditional therapy failed. We hypothesized that obstinate pain could be due to an increase in bone turnover associated with the formation of marginal bony outgrowths or enthesophytes. Injectable disodium clodronate is known to be highly efficacious in inhibiting bone reabsorption and is able to reduce several types of bone pain. The aim of the study was to evaluate the effectiveness of disodium clodronate in periarticular pathology of the hip in a group of patients resistant to traditional treatments and who were hypothesized to have a component of bone pain in their pain syndrome. Periarticular ultrasound examination is a useful method for detecting soft tissue alterations and is of interest in the study of these patients. In this study ultrasound examination showed periarticular alterations even when results of radiography were negative. Reduction in the hyperechoic ultrasound image, which confirms periarticular calcification, was observed in 75% of the patients treated with disodium clodronate vs. 33% of those treated with paracetamol. At the end of the study, all patients treated with disodium clodronate had a reduction in spontaneous and provoked pain > or = 1/3 vs. the basal visual analogue scale, unlike those treated with paracetamol. PMID- 11199342 TI - Consequences of price controls. PMID- 11199341 TI - Inhibition of NF kappa B activation by pyrrolidine dithiocarbamate prevents in vivo hypoxia/reoxygenation-mediated myocardial angiogenesis. AB - This study sought to examine the effect of nonlethal moderate whole body hypoxic challenge (10% 02/90% N2) on rat myocardial angiogenesis. Sprague Dawley rats were subjected to 4 h of systemic normobaric hypoxemic hypoxia (10 +/- 0.4% O2) in an anesthesia chamber or to 4 h of normoxia (ambient 20.9 +/- 0.4% O2) to time match the duration of hypoxia. All rats were then kept under normoxic conditions. Rats were sacrificed and hearts harvested either after 2 h for subsequent electrophoretic mobility gel shift assay for NF kappa B, or after 24 h for subsequent Western blot analysis for vascular endothelial growth factor (VEGF) and after 7 days for immunohistochemistry for capillary density measurement. We also used pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF kappa B, before 1 h of hypoxia to establish the possible role of NF kappa B in modulating myocardial angiogenesis. The results showed significant induction of VEGF protein expression after 4 h of hypoxia followed by 24 h of reoxygenation in the rat myocardium. The DNA binding activity of NF kappa B was increased compared with the hypoxic group. However inhibition of NF kappa B by PDTC decreased capillary density significantly when compared with the hypoxic group. These findings demonstrate the role of NF kappa B and VEGF in myocardial angiogenesis for the first time. PMID- 11199343 TI - Myositis of the quadriceps muscle group including vastus lateralis, vastus medialis, and rectus femoris. PMID- 11199344 TI - Resurfacing the patella offers lower complication and revision rates. PMID- 11199345 TI - Patella resurfacing during knee replacement remains controversial in Y2K. PMID- 11199346 TI - Removal of incarcerated braided titanium cables. PMID- 11199347 TI - Exercise treatment for sacroiliac pain. AB - The reciprocal relationship of the latissimus dorsi on one side and the gluteus maximus on the other side has been demonstrated anatomically. To demonstrate this relationship by muscle action, electromyographic studies were performed in 15 healthy individuals. This formed the baseline for evaluation of 5 symptomatic patients with sacroiliac dysfunction. Abnormal hyperactivity of the gluteus muscle on the involved side and increased activity of the latissimus on the contralateral side was contrasted with the normal function of the healthy individuals. All patients in the rotary strengthening exercise program improved in strength and return of myoelectric activity to more normal patterns. PMID- 11199348 TI - Arthrodesis with the Ilizarov device after failed knee arthroplasty. AB - Thirteen patients with failed total knee arthroplasty (TKA) due to infection (12 patients) or aseptic loosening (1 patient) underwent arthrodesis using the Ilizarov external fixator. Solid fusion was achieved in all patients with an average healing time of 27.6 weeks. Patients spent an average 18.8 weeks in the fixator followed by an average 8.8 weeks in a plaster cylinder cast. Five patients had a pin tract infection and one a superficial wound infection. One patient had 15 degrees recurvatum after surgery that was gradually corrected by adding a hinge system to the fixator. Average shortening of the affected limb was 3.7 cm (range: 1-6 cm). The Ilizarov fixator for knee arthrodesis after failed TKA produced favorable results and should be considered for use by surgeons familiar with the technique. PMID- 11199349 TI - Tension-band technique for ankle fusion. AB - A prospective study was conducted to develop a better technique for ankle fusion. Eleven consecutive patients were treated using the tension-band technique for ankle fusion and underwent follow-up for a minimum of 2 years (range: 2-5 years). All 11 patients achieved solid fusion for a fusion rate of 100%. Average time to fusion was 3 months (range: 2-6 months). The indication for ankle fusion was intractable aching pain that could not be controlled by conservative methods. Two of 11 patients underwent surgery due to infected arthritis. After ankle fusion, there was no recurrence of infection during a 3-year follow-up period. The technique included osteotomy of the bimalleoli from the inside out, removal of articular cartilage and preserving wedge space for cancellous bone grafting, with or without staple stabilization, and external immobilization supplementation. The functional outcome in all 11 patients improved from unsatisfactory preoperatively to satisfactory at latest follow-up (P<.001). No significant complications were noted. This simple technique proved excellent for ankle fusion with a satisfactory outcome and is recommended for treating severe ankle arthropathies. PMID- 11199350 TI - Recombinant human erythropoietin therapy for autologous blood donation in rheumatoid arthritis patients undergoing total hip or knee arthroplasty. AB - The effect of recombinant human erythropoietin on autologous blood donation was investigated in 73 rheumatoid arthritis patients who underwent hip or knee arthroplasty. Autologous blood donation of 400 mL was successful with recombinant human erythropoietin (12,000 U per week), and no homologous blood was required. The mean period of blood collection was 33.8 days. Mean hemoglobin levels were 9.7 g/dL before treatment, 10.7 g/dL before surgery, and 10.2 g/dL after surgery. This study confirmed recombinant human erythropoietin is effective for enabling preoperative blood donation in rheumatoid arthritis patients. PMID- 11199351 TI - Percutaneous sclerotherapy for congenital venous malformations in the extremities. AB - Between January 1991 and January 1998, a total of 15 patients underwent direct injection sclerotherapy for painful peripheral venous malformations. Duplex ultrasonography or venography was used in all cases for the detection and localization of tortuous venous structures. Direct injection with absolute ethyl alcohol was performed in 12 patients, and Sotradecol or sodium morrhuate was used in 5 patients. Provocative lidocaine testing was used in 2 patients in whom major nerves were in proximity to the malformations. All patients underwent follow-up in the clinic with duplex examination after each sclerotherapy. Clinical symptoms of all patients improved during average follow-up of 2.5 years (range: 3 months to 6 years.) Duplex examination was useful in detecting the venous component including the size and course of veins, which were often less well seen on magnetic resonance imaging. Duplex study was helpful in follow-up after sclerotherapy in all patients. Direct injection sclerotherapy is an acceptable treatment modality for venous malformations. Complications are manageable, and regular follow-up with Duplex is helpful. PMID- 11199352 TI - Human immunodeficiency virus testing for elective orthopedic procedures: results in a community-based hospital. AB - Between January 1, 1989 and July 31, 1995, voluntary preoperative screening tests for human immunodeficiency virus (HIV) infection, using an enzyme-linked immunosorbant assay, were completed on 2,727 patients who underwent elective orthopedic surgical procedures. There were 2,719 (99.7%) negative, 4 (0.15%) positive, and 3 (0.11%) false-positive results; 1 test was indeterminate (0.04%). All 4 positive patients were men with a mean age of 32 years (range: 26-43 years). Although the prevalence of positive tests is low in this setting, voluntary testing alerts the surgeon to higher risk patients, does not sacrifice patient care, and enables the incorporation of more extensive precautionary measures in the operating room to minimize occupational risks to the surgical team. PMID- 11199353 TI - Anatomic considerations of the posterolateral lumbar disk region. AB - Sixteen embalmed cadavers were dissected to determine the location of the lumbar nerve root and sympathetic trunk with reference to the superior border of transverse process. In the posterolateral lumbar disk region, a safe zone was found between the anterior limit of the lumbar nerve and the posterior limit of the sympathetic trunk. It has a transverse dimension of 22 mm at the T12-L1 disk region and 25 mm at the L4-L5 disk region. The only exception to this was the genitofemoral nerve running close to the lateral margin of the L2-L3 disk. The study provides an understanding of the posterolateral orientation of the lumbar nerves and sympathetic trunk. PMID- 11199354 TI - Cryptococcal osteomyelitis with septic arthritis. PMID- 11199355 TI - Distal radioulnar synostosis following K-wire fixation. PMID- 11199356 TI - Thrombosis of the brachial vein and pulmonary embolism after subacromial decompression of the shoulder. PMID- 11199357 TI - Upper extremity fractures and Parkinson's disease. PMID- 11199358 TI - Bone marrow edema syndrome. PMID- 11199359 TI - Trends, controversies and contradictions in the management of gastroesophageal reflux disease patients. PMID- 11199360 TI - Effect of elimination of acid reflux on epithelial cell proliferative activity of Barrett esophagus. AB - BACKGROUND: Barrett esophagus (BE) is a premalignant condition resulting from chronic acid gastroesophageal reflux and is associated with increased epithelial cell proliferation. Elimination of acid reflux might decrease cancer risk by affecting cell proliferation in BE. The effect of elimination of acid reflux on epithelial cell proliferation in BE was studied. METHODS: Forty-five patients with long segment Barrett esophagus were treated in a randomized 2-year follow-up study with either omeprazole 40 mg b.i.d. (OME) or ranitidine 150 mg b.i.d. (RAN) and were compared for the effect on epithelial cell proliferation. Biopsies were taken 3 cm above the GE junction and just below the Z-line, at 0, 3, 9, and 24 months. Epithelial cell proliferation was determined by in vitro labeling with 5 bromo-2-deoxyuridine and immunohistochemistry. Labeling indices (LI) were established for luminal and crypt epithelium separately. Ambulatory 24-h esophageal pH-metry was performed at 0 and 3 months. Comparisons were made for the timeframes 0-3 months, 3-24 months, and 0-24 months. RESULTS: OME reduced mean acid reflux to 0.1 %/24 h, RAN to 9.4%. In the distal and the proximal biopsies, change in LI after 3 months was n.s. at either level for both treatments. In the distal biopsies (OME 22, RAN 23 patients) luminal LI increased significantly for RAN from 3 to 24 months (+12.64% month, mean area under the curve (AUC)), while that for OME remained stable, RAN versus OME P < 0.05. Crypt LI increased in both groups, only in RAN significantly so (+30.75% month), RAN versus OME n.s. In the proximal biopsies luminal LI at 24 months (OME 20, RAN 21 patients) had increased slightly but not significantly in RAN (+8.86% month), RAN versus OME n.s., whereas in the crypts LI in OME it had increased significantly (+28.80% month), OME versus RAN n.s. CONCLUSION: Elimination of acid reflux resulted in a stabilization of luminal cell proliferative activity of Barrett epithelium in the distal esophagus, whereas this activity increased during continued acid reflux. Whether this finding has any implication for the cancer risk in Barrett esophagus remains to be seen. PMID- 11199361 TI - Rabeprazole, 20 mg once daily or 10 mg twice daily, is equivalent to omeprazole, 20 mg once daily, in the healing of erosive gastrooesophageal reflux disease. AB - BACKGROUND: Proton pump inhibitors are the most potent pharmacologic inhibitors of gastric acid secretion currently available, and have proven effective in the treatment of gastro-oesophageal reflux disease (GERD). The object of this study was to compare the efficacy and tolerability of a new proton pump inhibitor, rabeprazole at two different dosages, with that of omeprazole in the healing of erosive GERD. METHODS: Rabeprazole 20 mg once daily (QD) and 10 mg twice daily (BID) were compared with omeprazole 20 mg QD in a double-blind, multicentre, parallel group study involving 310 patients with erosive GERD. The primary efficacy endpoint was oesophageal mucosal healing determined by endoscopy. Secondary endpoints included reduction in symptoms and improvements in quality-of life scores. RESULTS: The healing rates between both rabeprazole groups and the omeprazole group were equivalent in both the per-protocol and intent-to-treat populations. In the per-protocol population, rabeprazole 20 mg was noted to have a numerical trend toward more rapid daytime heartburn relief. However, by 4 and 8 weeks of treatment, no significant differences were found between groups for secondary endpoints, adverse events, or laboratory abnormalities including elevation of serum gastrin levels. CONCLUSIONS: Rabeprazole 20 mg in two different dosing schedules is as effective as omeprazole 20 mg QD with regard to efficacy and tolerability in patients with erosive GERD. PMID- 11199362 TI - No evidence of an association between Helicobacter pylori infection and Raynaud phenomenon. AB - BACKGROUND: Raynaud phenomenon (RP) is a vasospastic condition that manifests itself as cold-induced ischemic attacks of the fingers with skin color changes. It may be classified as primary (PRP) or secondary (SRP), if associated to other diseases, mainly connective-tissue diseases. Recently, the association between PRP and Helicobacter pylori infection has been reported. The aims of this study were to evaluate the prevalence of gastric H. pylori infection in a large group of patients affected by PRP and SRP and to assess whether it was more evident in patients with more recent onset of RP. METHODS: Ninety-eight consecutive patients (93 F and 5 M), referring to our videocapillaroscopic service for the diagnosis of vascular and connective-tissue diseases, were evaluated. Forty-nine of them were affected by PRP and 49 by SRP. Patients were classified as having PRP on the basis of normal serological and immunological findings, normal videocapillaroscopic examination and exclusion of other conditions inducing RP. H. pylori infection was diagnosed by 13C-urea breath test (UBT). Two groups of 49 age-and sex-matched controls, respectively, were also evaluated. RESULTS: Patients with SRP resulted significantly older than those with PRP (P < 0.006). UBT was found positive in 22/49 patients with PRP (45%) and in 29/49 patients with SRP (59%). The positivity of the respective control groups was 36% and 53% (P = NS). There was no higher prevalence of H. pylori infection in patients with RP lasting for less than 4 years. CONCLUSIONS: The results do not confirm the previously reported high prevalence of H. pylori infection in patients with PRP. A high association was not even found between the presence of the microorganism and SRP. There was no difference in the prevalence of H. pylori infection among the subgroups with more recent onset of both PRP and SRP. PMID- 11199363 TI - Effect of white wine on esophageal peristalsis and acid clearance. AB - BACKGROUND: In a previous study it was demonstrated that white wine reduces the lower esophageal sphincter pressure and induces gastroesophageal reflux characterized by reflux episodes of long duration. In the present study, it was evaluated whether wine disturbs esophageal peristalsis and acid clearance. METHODS: Twelve healthy volunteers (7F, 23-37 years) received 300 ml white wine (8% vol/vol; WW), an ethanol solution (8% vol/vol; ET) or tap water (WA) together with a standardized meal in a random order. Acid clearance was tested by instillation of 15 ml 0.1 N HCI into the distal esophagus. The number of swallows (dry swallow every 30 sec) were counted until pH rose again above 5. Five wet swallows (5 ml) were applied to test primary peristalsis and five insufflations of 20 ml of air were performed to test secondary peristalsis. Each test was done immediately after and 60 min after ingestion of the beverages. RESULTS: A significantly higher number of swallows were needed to clear the esophagus immediately after ingestion of wine (P < 0.01; median number: WW 12; ET 8; WA 7) due to an increase in the frequency of failed, simultaneous, and low-amplitude contractions. The frequency of triggered secondary contractions was decreased (P < 0.02; WW 70%; ET 100%; WA 100%) and the latency between air injection and onset of secondary peristalsis was prolonged (P < 0.05; WW 9 sec; ET 7 sec; WA 6 sec) immediately after ingestion of white wine. Wet swallow induced primary peristalsis was not influenced by wine. No significant differences in the measured parameters were seen 60 min after ingestion of the three beverages. CONCLUSION: White wine disturbs temporarily esophageal clearance due to a disturbance of triggering secondary peristalsis and due to an increase in ineffective contractions. The ethanol content alone is not responsible for the effects of white wine on esophageal peristalsis and acid clearance. PMID- 11199364 TI - Intragastric CO2 and nitric oxide participate in the regulation of peptone induced gastrin release in humans. AB - BACKGROUND: Moderate acidification of the gastric lumen inhibits peptone-induced gastrin release. The aim of the present study was to investigate if the gastric acid neutralization products CO2 (from secreted HCO3) and NO (from reduced salivary nitrite) could act as intermediate messengers between luminal acidity and the inhibition of peptone-induced gastrin release. METHODS: Fourteen healthy volunteers (mean age, 27 years; range, 20-39 years; 3 women) participated in the study. Intragastric perfusion with saline or peptone was performed on the healthy volunteers. Venous blood samples were analyzed for serum gastrin concentrations. Intragastric NO was measured by chemiluminescence. RESULTS: Basal serum gastrin ranged between 11 and 23 pmol/l. Peptone in Sorensen's phosphated buffer (pH 6.9, PCO2 0 mmHg) increased serum gastrin by 83% +/- 23%, whereas acidified peptone (pH 2.0) did not stimulate gastrin release. Acidified peptone buffered with NaHCO3 to neutrality (pH 6.9, PCO2 approximately 600 mmHg) increased serum gastrin by 166% +/- 29%. Low intragastric NO levels were obtained by deviation of saliva. During such salivary depletion, acidified peptone (pH 2.0) stimulated gastrin release to a level of about 40% of the control response (pH 6.9). This peptone-induced gastrin response during salivary deviation was inhibited by addition of nitrite to the perfusate. CONCLUSIONS: Acid-induced inhibition of peptone-stimulated gastrin release is partly dependent on intraluminal NO formed in the reaction between salivary nitrite and gastric acid. In addition, the gastric acid neutralization product CO2 seems to potentiate the effect of peptone on gastrin release. PMID- 11199365 TI - Probiotic therapy fails to improve gut permeability in a hapten model of colitis. AB - BACKGROUND: Studies in clinical and experimental inflammatory bowel disease (IBD) have shown disturbances in intestinal bacterial flora with an increase in potentially pathogenic and a decrease in protective organisms. It was hypothesized that Lactobacillus plantarum species 299 (LP299), a probiotic, would ameliorate colitis and improve intestinal permeability in experimental colitis. This study investigated the effect of LP299 in the trinitrobenzenesulfonic acid/ethanol (TNBS/E) rat model of colitis. METHODS: Twelve week old male Wistar rats were randomized to receive rectal instillates of either TNBS/E (n = 48) or saline (n = 16). For the next 7 days the animals were gavaged with 2.5 ml of oat fibre suspension containing 10(9) colony forming units (CFU) of LP299 (LP299/OF), oat fibre suspension alone (OF) or no treatment. At the end of the experiment rats received radiolabelled polyethylene glycol and urine was collected for 24 h to assess permeability. Animals were then anaesthetized and colons were harvested for colon macroscopic scoring (CMS). RESULTS: TNBS/E per rectum resulted in a greater CMS (P < 0.001) and gut permeability (P = 0.006) than saline. Administration of LP299/OF or oat fibre alone did not result in a reduction in CMS or gut permeability when compared to colitic controls. CONCLUSIONS: LP299/OF, when administered after TNBS instillation, does not reduce the severity of colitis or improve gut permeability in this hapten model of colitis. PMID- 11199366 TI - Disease outcome in inflammatory bowel disease: mortality, morbidity and therapeutic management of a 796-person inception cohort in the European Collaborative Study on Inflammatory Bowel Disease (EC-IBD). AB - BACKGROUND: The course of inflammatory bowel diseases (IBD) has mainly been studied using different methods in single patient cohorts. The aim of the present study was to assess clinical aspects of disease outcome in a population-based cohort of IBD patients over a 4-year period in multiple centres across Europe. METHODS: A total of 796 patients with IBD diagnosed in 10 centres between October 1991 and October 1993, registered at the EC IBD study centre (98% of the original cohort), participated in the study. Investigators filled out a standard follow-up form containing questions on the method of follow-up, vital status of the patient, change in diagnosis, extraintestinal manifestations, medical and surgical treatment, and physician's global assessment of disease activity. RESULTS: Complete relief of the complaints was reported in 255 (48%) patients with ulcerative colitis (UC), 9 (50%) with indeterminate colitis (IC), but only in 87 (35%) of patients with Crohn disease (CD). Improvement was reported in 195 (37%) patients with UC, 113 (45%) with CD and 6 (33%) with IC. During the 4-year follow-up period, 23 patients died (14 UC, 8 CD. and 1 IC). The mean age at death was 69.3 years (s, 14.9 years). The deaths of three patients were recorded as directly due to IBD. CONCLUSIONS: With the present approach to therapeutic management the short-term outcome of patients with IBD seems to be favourable in 10 medical centres in the north and south of Europe. However, more detailed studies including both objective and subjective measures are necessary. PMID- 11199367 TI - Fas/Fas ligand expression and characteristics of primed CD45RO+ T cells in the inflamed mucosa of ulcerative colitis. AB - BACKGROUND: Chronic immune activation in the colon is characteristic of ulcerative colitis (UC). Fas/Fas ligand (FasL) system is a mechanism responsible for activation-induced cell death (AICD), which maintains homeostasis within the immune system. Thus, Fas/FasL expression on activated colonic T cells of UC patients, as well as the susceptibility of such T cells to AICD was investigated in order to determine the role of activated colonic T cells in the long lasting inflammation in UC. METHODS: Fas, FasL, and CD45RO expression on peripheral blood and colonic T cells of UC patients were assayed by flow cytometry. Apoptosis of colonic T cells induced by anti Fas antibody was assessed using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay. RESULTS: The majority of colonic T cells expressed both CD45RO and Fas in the colonic mucosa, a situation that was quite different from that in the peripheral blood. The number of CD45RO+CD8+ and Fas+CD8+ T cells was significantly lower in UC patients than the controls, unlike the number of Fas+CD4+ T cells. In contrast, the number of both CD45RO+CD4+ and CD45RO+CD8+ T cells in UC mucosa expressing FasL was significantly higher than in the controls. While Fas mediated apoptosis of CD45RO+CD8+ T cells was higher in UC patients than the controls, the number of apoptotic CD45RO+CD4+ T cells from UC mucosa was not. CONCLUSIONS: In UC patients, CD45RO+CD4+ T cells are less sensitive to apoptotic signals mediated by Fas. These phenomena may contribute to the pathogenesis of UC. PMID- 11199368 TI - Impact of screening examinations on survival in familial adenomatous polyposis. AB - BACKGROUND: Prophylactic family screening and surgery has improved the outcome of patients with familial adenomatous polyposis (FAP) largely preventing deaths due to colorectal cancer. The present study compared the mortality rates and causes of death of FAP patients diagnosed by symptoms (probands) or by family screening (call-up). METHODS: The study comprised all 236 FAP patients registered in the Finnish Polyposis Registry until the end of June 1998. There were 116 probands and 120 call-up patients with a median age of 36.8 and 22.8 at diagnosis and median follow-up times of 6.3 and 9.9 years, respectively. Cumulative crude and relative survival estimates were calculated for each group and the causes of death were determined. RESULTS: The life expectancy was significantly better in the call-up group than in the probands after colectomy (P < 0.001). The survival rates of the call-up group equaled those expected for a comparable group in the general population up to 18 years after colectomy. The main cause of death was colorectal cancer accounting for 54 out of 68 deaths: four in the call-up group (all rectal stump cancer) and 50 in probands. Upper GI-tract cancer caused four deaths (periampullary cancer two, stomach cancer two) and two deaths were due to postoperative pulmonary embolism. CONCLUSION: The survival of FAP patients is significantly improved by prophylactic screening and surgery. Further improvement may be possible by using restorative proctocolectomy instead of colectomy and ileorectal anastomosis and by regular upper GI-tract endoscopic surveillance. PMID- 11199369 TI - Incidence and associated factors of neutralizing anti-interferon antibodies among chronic hepatitis C patients treated with interferon in Taiwan. AB - BACKGROUND: The administration of interferon (IFN) could be complicated by the development of neutralizing anti-interferon antibodies (NA). This study evaluates the frequency and associated factors of NA among chronic hepatitis C patients treated with different IFNs. METHODS: Ninety-five chronic hepatitis C patients were randomized to be treated with recombinant IFN-alpha2a (n = 28), IFN-alpha2b (n = 39) or lymphoblastoid IFN-alpha1 (n = 28) given intramuscularly, 3-6 million units, thrice weekly for 24 weeks. Serum samples collected before, during and after the cessation of treatment were checked for NA. RESULTS: Three patients were withdrawn from treatment. All patients were negative for NA before treatment and 13 (14%) patients developed neutralizing antibodies. Of the 26 patients treated with IFN-alpha2a, 6 (23.1%) developed NA. whereas NA were detected in only 6 (15.4%) of 39 and 1 (3.7%) of 27 patients treated with IFN-alpha2b and IFN alphanl, respectively. Age, gender, HCV genotype, ALT level, IFN total dose and liver histology were not associated with the development of NA. By using multivariate logistic regression it was shown that pretreatment HCV RNA level and IFN preparation were the two major factors related to the production of NA. The response of treatment was related to pretreatment viremia but not to the presence of NA. CONCLUSIONS: The frequency of development of NA among Taiwanese patients with chronic hepatitis C might be related to different IFN preparations and pretreatment HCV RNA level. The response of treatment was related to pretreatment HCV RNA level but not to the presence of NA. PMID- 11199370 TI - In situ expression of transforming growth factor-beta1-3, latent transforming growth factor-beta binding protein and tumor necrosis factor-alpha in liver tissue from patients with chronic hepatitis C. AB - BACKGROUND: The mechanisms determining liver damage in chronic hepatitis C remain unclear. The aim was to evaluate the in situ expression of transforming growth factor beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha), two key cytokines implicated as important pathogenic mediators in the development of liver fibrosis. METHODS: In situ expression of TNF-alpha and of TGF-beta isoforms 1-3, and its transport protein latent TGF-beta binding protein (LTBP), was determined by immunohistochemistry in 9 untreated patients with chronic hepatitis C infection and in 6 controls without liver disease. In addition, TGF-beta1 expression was analyzed in 10 HCV patients before and after treatment with interferon-alpha alone, or in combination with ribavirin. RESULTS: Liver biopsies from HCV patients showed positive staining for TGF-beta1-3 isoforms and LTBP, and to a lesser degree for TNF-alpha, in areas with inflammation and fibrosis. Normal control liver showed no positive staining. TGF-beta1 expression before treatment, quantified by morphometric analysis, did not differ between non-responders and sustained responders. In patients responding to therapy, TGF-beta1 expression decreased in parallel with histological improvement, while no difference in TGF beta1 expression was seen before and after treatment in non-responders. CONCLUSION: These results suggest that TNF-alpha and all three isoforms of TGF beta are involved in the pathogenesis of HCV related liver disease, and that treatment leading to eradication of the virus affects the expression of TGF beta1. PMID- 11199371 TI - The clinical expression of hemochromatosis in Oslo, Norway. Excessive oral iron intake may lead to secondary hemochromatosis even in HFE C282Y mutation negative subjects. AB - BACKGROUND: The prevalence of hereditary hemochromatosis in Norway is one of the highest reported in the world. However, the clinical presentation in patients with hemochromatosis in Norway seems to be different compared with recent studies elsewhere. The aim of this study was to investigate patients with hemochromatosis in one community hospital in Norway and to study the prevalence of the C282Y mutation. METHODS: One hundred and twenty patients were consecutively admitted to one medical department in Oslo. Serum transferrin and ferritin concentrations were measured in all patients, and a percutaneous liver biopsy was obtained in 108 of 120 (90%) patients. Stainable iron (Perls stain) in hepatocytes was graded from 0 to 4+ and fibrosis from 1 to 4. Genotyping for the C282Y and H63D mutation in the HFE gene was performed by PCR-RFLP. RESULTS: Forty-eight (40%) of the patients suffered from tiredness and astenia and 29 (24%) had typical arthropathy. Only 5 of 105 (4.5%) had biopsy confirmed cirrhosis and 5 had diabetes mellitus. Patients referred from a blood bank had significantly less symptoms and signs compared with other patients. Twenty-one of 120 (17.5%) patients were C282Y mutation negative. Seventeen (81%) of these patients (16 women and 1 man) had a history of extensive oral iron intake lasting from 5 to 50 years. When excluding those with extensive oral iron intake (n = 17), 92 of 103 (89%) were homozygous for the C282Y mutation, 7 (7%) were heterozygous including 3 compound heterozygous and 4 (4%) were mutation negative. CONCLUSIONS: Only a minority of our patients with hemochromatosis had a far advanced disease at the time of diagnosis (less than 5% had cirrhosis) and hemochromatosis in a majority of the C282Y mutation negative patients was associated with excessive oral iron intake for several years. PMID- 11199373 TI - Gut permeability in patients with acute pancreatitis. AB - BACKGROUND: The bacterial contamination of pancreatic necrosis in acute pancreatitis is supposed to occur through translocation of intestinal bacteria. Increased gut permeability may be the initial phenomenon in this process. To test the hypothesis that gut permeability is increased in acute pancreatitis a clinical study was made where gut absorption and permeability were assessed with multi-sugar probes in patients with acute pancreatitis within 2 days after admission to hospital and again after recovery of disease. METHODS AND RESULTS: Twenty-three patients with acute pancreatitis and 20 healthy controls were studied. According to Atlanta classification, 15 patients had mild and 8 patients severe pancreatitis. Gut absorption, assessed as the 5-h urine excretion of L rhamnose, D-xylose and 3-O-methylglucose, was decreased in patients with acute pancreatitis and more pronounced in patients with severe pancreatitis (L-rhamnose and D-xylose: P < 0.001; 3-O-methylglucose: P < 0.05). Gut permeability, assessed as the ratio of lactulose/L-rhamnose, was increased in severe pancreatitis (0.16 +/- 0.13, 0.07 +/- 0.03, 0.04 +/- 0.04; severe pancreatitis, mild pancreatitis, controls, respectively; P < 0.001 between three groups, P < 0.05 between pancreatitis groups). CONCLUSIONS: Gut absorption capacity is decreased and gut permeability is increased in patients with acute pancreatitis. Patients with severe pancreatitis may be more exposed to impaired gut barrier function. PMID- 11199372 TI - Chronic inhibition of nitric oxide ameliorates splanchnic hyposensitivity to glypressin in a hemorrhage-transfused rat model of portal hypertension. AB - BACKGROUND: Vasopressin given during hemorrhage is less effective than when given during a stable state in experimental portal hypertension or patients with cirrhosis (the so-called hyposensitivity phenomenon). This study investigated whether chronic inhibition of nitric oxide (NO) synthesis by NG-nitro-L-arginine methyl ester (L-NAME), a non-selective NO synthase inhibitor, could potentiate the portal-hypotensive effect of glypressin (a long-acting vasopressin analogue) in portal-hypertensive rats during acute bleeding status. METHODS: Portal hypertension was induced by partial portal vein ligation (PVL). Rats were divided to receive either L-NAME (approximately 25 mg/kg/day in tap water) or placebo (tap water) treatment orally from 2 days prior to until 14 days after the operation. At the end of treatment, L-NAME-and placebo-treated PVL rats were subdivided into without-bleeding and with-bleeding groups to assess the effects of glypressin (0.07 mg/kg) on systemic and portal hemodynamics. In rats with a hypotensive hemorrhage, 4.5 ml of blood was withdrawn and 50% of the withdrawn blood was reinfused before the administration of glypressin. RESULTS: As compared with placebo-treated rats, chronic treatment with L-NAME in PVL rats significantly increased mean arterial pressure (P < 0.001) without modulating portal pressure (P > 0.05). In placebo-treated PVL rats, glypressin resulted in a less decrease in portal pressure in rats with bleeding than in those without bleeding (P < 0.05). For PVL rats with bleeding, the portal-hypotensive effect of glypressin was significantly potentiated after chronic L-NAME treatment (P < 0.05). CONCLUSIONS: Chronic inhibition of NO alleviates the splanchnic hyposensitivity to glypressin observed in bleeding PVL rats, suggesting the pathophysiological role of nitric oxide in mediating this splanchnic hyposensitivity. PMID- 11199374 TI - Buprenorphine or procaine for pain relief in acute pancreatitis. A prospective randomized study. AB - BACKGROUND: To assess the analgesic efficacy and side effects of buprenorphine and procaine in patients with acute pancreatitis. METHODS: Forty patients (average age, 50 years; 23 male) with acute pancreatitis or an acute bout of a chronic pancreatitis were prospectively randomized to receive buprenorphine or procaine for pain relief. Both analgesics were administered as constant intravenous (i.v.) infusions and additional analgesics were given on demand. Pain scores were assessed on a visual analogue scale. Close clinical control and laboratory checks were performed during the three-day study period. RESULTS: Patients receiving buprenorphine were significantly less likely to demand additional analgesics (1 versus 14 patients; P < 0.0001). The pain scores for patients in the buprenorphine group were significantly lower over the treatment period in comparison to procaine (P < 0.05). The reduction of pain score was significantly greater during the initial two treatment days using buprenorphine (day 1: 55 versus 25, P < 0.0001; day 2: 62 versus 40, P = 0.005). Side effects were comparable for both groups with the exception of a slightly higher sedation rate under buprenorphine. CONCLUSIONS: Constant i.v. application of buprenorphine is more effective than the recommended procaine for pain relief in acute pancreatitis. PMID- 11199375 TI - Pancreatic ductal morphological pattern and dilatation in postoperative abdominal pain in patients with congenital choledochal cyst: an analysis of postoperative pancreatograms. AB - BACKGROUND: Postoperative abdominal pain associated with pancreatitis has been reported as a pancreas-associated complication after total biliary excision. The aim of the present study was to determine pancreatic ductal patterns in the head of the pancreas and evaluate pancreatic ductal dilatation in patients presenting with postoperative abdominal pain after radical biliary excision for congenital choledochal cyst. METHODS: Postoperative endoscopic retrograde pancreatography (ERP) was performed in a total of 38 patients (27 female and 11 male) with a history of postoperative abdominal pain or an increase in serum and urinary amylase on laboratory analysis. Pancreatic ductal configuration and ductal dilatation were determined. RESULTS: Pancreatic configurations included the usual type (n = 20), ansa pancreatica type (n = 11), loop type (n = 5), and divisum type (n = 2). Dilatation of the pancreatic duct was observed in 34 patients. The common channel was dilated in 29 patients. Mild postoperative pancreatitis occurred in 4 patients in the long term. Protein plugs were observed in the dilated pancreatic duct. CONCLUSIONS: Pancreatic ductal morphological pattern and ductal dilatation, possibly caused by long-standing stagnation of the pancreatic juice, may be associated with postoperative abdominal pain and pancreatitis in congenital choledochal cyst. PMID- 11199376 TI - Mucin ball-producing extrahepatic bile duct carcinoma. AB - The characteristic features of surgically curable mucin-producing extrahepatic bile duct carcinoma (MPEBC) have not previously been elucidated. Three (6.5%) of 46 patients who underwent surgery in our department for bile duct carcinoma between 1986 and 1997 had MPEBC. Clinicopathological features, diagnostic procedures and operative methods for patients with MPEBC were investigated. Tumors in the bile duct were identified by cholangioscopy combined with cholangiography after removal of mucin balls. Tumors were located close to the hepatic confluence in these patients. Two patients underwent hepatic lobectomy together with caudate lobectomy while the other underwent resection of the hepatic confluence. Absence of residual tumors was confirmed histologically in these patients. All three patients remain alive without evidence of recurrence, 22-54 months after surgery. MPEBC is a curable disease. Accurate localization in the biliary tree is essential and can only be obtained after, i) removal of mucin balls, and ii) extensive diagnostic work-up including cholangiography, cholangioscopy and intraoperative pathological examination. PMID- 11199377 TI - Mass spectrometric studies of elusive molecules that contain an N(+)-X- bond. AB - This review will be concerned with the gas phase chemistry of 1,2- and 1,3 dipolar systems that contain a carbon-nitrogen bond. Although most of these compounds are stable molecules under normal conditions, certain congeners are reactive species that cannot be prepared using conventional procedures. The isolation and observation of these elusive compounds therefore require appropriate experimental conditions such as those provided by the gas phase of a mass spectrometer. In these experiments, the radical cations, corresponding to the molecule under study, must be prepared via indirect procedures, including dissociative electron ionization, on-line flash-vacuum pyrolysis-mass spectrometry, or ion-molecule reactions. Their characterization is mainly based on collisional activation and ion-molecule reactions. The formation of the corresponding highly reactive neutrals is attempted by neutralization reionization mass spectrometry. This review presents more than one hundred different molecules together with their methods of preparation and the experiment used to identify them. PMID- 11199378 TI - New separation tools for comprehensive studies of protein expression by mass spectrometry. AB - Mass spectrometry has emerged as a core technique for protein identification and characterization because of its high sensitivity, accuracy, and speed of analysis. The most widespread strategy for studying global protein expression in biological systems employs analytical two-dimensional polyacrylamide gel electrophoresis (2D PAGE) followed by enzymatic degradation of isolated protein spots, peptide mapping, and bioinformatics searches. Using this method, thousands of proteins can be resolved in a gel and their expression quantified. However, certain types of proteins possessing important cellular functions are not easily analyzed using this strategy. These proteins include membrane, low copy number, highly basic, and very large (> 150 kDa) and small (< 10 kDa) proteins. To meet the growing need to simultaneously monitor all types of proteins in a biological system, new separation strategies have emerged that are amenable to hyphenation to mass spectrometric techniques. This article will review these new techniques and examine their usefulness in studies of protein expression. PMID- 11199379 TI - Applications and mechanisms of charge-remote fragmentation. AB - Studies on the applications, energetics, and mechanisms of charge-remote fragmentations are reviewed, with emphasis given to those articles published after 1992. Independent of the charge status, charge-remote fragmentations are analogous to gas-phase thermolysis. Under collisional activation and with a fixed charge, ions containing long-chain or poly-ring structures undergo charge-remote fragmentations, generating productions that are structurally informative. Interpretation of the production spectra enables one to elucidate molecular structures. Although charge-remote fragmentations have been successfully used in the structural determination of fatty acids, phospholipids, glycolipids, triacylglycerols, steroids, peptides, ceramides, and other systems, the energetics and mechanisms of these reactions are still debated because none of the existing mechanisms can explain all the experimental data. PMID- 11199380 TI - Malignant pleural mesotheliomas: an environmental health risk in southeast Turkey. PMID- 11199381 TI - Preparing for a JCAHO survey: Part 5. PMID- 11199382 TI - Raising the bar: improving standards for social work practice in long-term care. PMID- 11199383 TI - Survey finds health care workers short on commitment to employers. PMID- 11199384 TI - Corporate compliance: the social work role. PMID- 11199385 TI - After discharge planning: taking a leadership role in community outreach. PMID- 11199386 TI - Programmed cell death of tracheary elements as a paradigm in plants. AB - Plant development involves various programmed cell death (PCD) processes. Among them, cell death occurring during differentiation of procambium into tracheary elements (TEs), which are a major component of vessels or tracheids, has been studied extensively. Recent studies of PCD during TE differentiation mainly using an in vitro differentiation system of Zinnia have revealed that PCD of TEs is a plant-specific one in which the vacuole plays a central role. Furthermore, there are recent findings of several factors that may initiate PCD of TEs and that act at autonomous degradation of cell contents. Herein I summarize the present knowledge about cell death program during TE differentiation as an excellent example of PCD in plants. PMID- 11199387 TI - Programmed cell death in cereal aleurone. AB - Progress in understanding programmed cell death (PCD) in the cereal aleurone is described. Cereal aleurone cells are specialized endosperm cells that function to synthesize and secrete hydrolytic enzymes that break down reserves in the starchy endosperm. Unlike the cells of the starchy endosperm, aleurone cells are viable in mature grain but undergo PCD when germination is triggered or when isolated aleurone layers or protoplasts are incubated in gibberellic acid (GA). Abscisic acid (ABA) slows down the process of aleurone cell death and isolated aleurone protoplasts can be kept alive in media containing ABA for up to 6 months. Cell death in barley aleurone occurs only after cells become highly vacuolated and is manifested in an abrupt loss of plasma membrane integrity. Aleurone cell death does not follow the apoptotic pathway found in many animal cells. The hallmarks of apoptosis, including internucleosomal DNA cleavage, plasma membrane and nuclear blebbing and formation of apoptotic bodies, are not observed in dying aleurone cells. PCD in barley aleurone cells is accompanied by the accumulation of a spectrum of nuclease and protease activities and the loss of organelles as a result of cellular autolysis. PMID- 11199388 TI - Programmed cell death in plant reproduction. AB - Reproductive development is a rich arena to showcase programmed cell death in plants. After floral induction, the first act of reproductive development in some plants is the selective killing of cells destined to differentiate into an unwanted sexual organ. Production of functional pollen grains relies significantly on deterioration and death of the anther tapetum, a tissue whose main function appears to nurture and decorate the pollen grains with critical surface molecules. Degeneration and death in a number of anther tissues result ultimately in anther rupture and dispersal of pollen grains. Female sporogenesis frequently begins with the death of all but one of the meiotic derivatives, with surrounding nucellar cells degenerating in concert with embryo sac expansion. Female tissues that interact with pollen undergo dramatic degeneration, including death, to ensure the encounter of compatible male and female gametes. Pollen and pistil interact to kill invading pollen from an incompatible source. Most observations on cell death in reproductive tissues have been on the histological and cytological levels. We discuss various cell death phenomena in reproductive development with a view towards understanding the biochemical and molecular mechanisms that underlie these processes. PMID- 11199389 TI - Programmed cell death during endosperm development. AB - The endosperm of cereals functions as a storage tissue in which the majority of starch and seed storage proteins are synthesized. During its development, cereal endosperm initiates a cell death program that eventually affects the entire tissue with the exception of the outermost cells, which differentiate into the aleurone layer and remain living in the mature seed. To date, the cell death program has been described for maize and wheat endosperm, which exhibits common and unique elements for each species. The progression of endosperm programmed cell death (PCD) in both species is accompanied by an increase in nuclease activity and the internucleosomal degradation of nuclear DNA, hallmarks of apoptosis in animals. Moreover, ethylene and abscisic acid are key to mediating PCD in cereal endosperm. The progression of the cell death program in developing maize endosperm follows a highly organized pattern whereas in wheat endosperm, PCD initiates stochastically. Although the essential characteristics of cereal endosperm PCD are now known, the molecular mechanisms responsible for its execution remain to be identified. PMID- 11199390 TI - Regulation of cell death in flower petals. AB - The often rapid and synchronous programmed death of petal cells provides a model system to study molecular aspects of organ senescence. The death of petal cells is preceded by a loss of membrane permeability, due in part to increases in reactive oxygen species that are in turn related to up-regulation of oxidative enzymes and to a decrease in activity of certain protective enzymes. The senescence process also consists of a loss of proteins caused by activation of various proteinases, a loss of nucleic acids as nucleases are activated, and enzyme-mediated alterations of carbohydrate polymers. Many of the genes for these senescence-associated enzymes have been cloned. In some flowers, the degradative changes of petal cells are initiated by ethylene; in others, abscisic acid may play a role. External factors such as pollination, drought and temperature stress also affect senescence, perhaps by interacting with hormones normally produced by the flowers. Signal transduction may involve G-proteins, calcium activity changes and the regulation of protein phosphorylation and dephosphorylation. The efficacy of the floral system as well as the research tools now available make it likely that important information will soon be added to our knowledge of the molecular mechanisms involved in petal cell death. PMID- 11199391 TI - Hypersensitive response-related death. AB - The hypersensitive response (HR) of plants resistant to microbial pathogens involves a complex form of programmed cell death (PCD) that differs from developmental PCD in its consistent association with the induction of local and systemic defence responses. Hypersensitive cell death is commonly controlled by direct or indirect interactions between pathogen avirulence gene products and those of plant resistance genes and it can be the result of multiple signalling pathways. Ion fluxes and the generation of reactive oxygen species commonly precede cell death, but a direct involvement of the latter seems to vary with the plant-pathogen combination. Protein synthesis, an intact actin cytoskeleton and salicylic acid also seem necessary for cell death induction. Cytological studies suggest that the actual mode and sequence of dismantling the cell contents varies among plant-parasite systems although there may be a universal involvement of cysteine proteases. It seems likely that cell death within the HR acts more as a signal to the rest of the plant rather than as a direct defence mechanism. PMID- 11199392 TI - Transgene-induced lesion mimic. AB - Lesion mimic, i.e., the spontaneous formation of lesions resembling hypersensitive response (HR) lesions in the absence of a pathogen, is a dramatic phenotype occasionally found to accompany the expression of different, mostly unrelated, transgenes in plants. Recent studies indicated that transgene-induced lesion formation is not a simple case of necrosis, i.e., direct killing of cells by the transgene product, but results from the activation of a programmed cell death (PCD) pathway. Moreover, activation of HR-like cell death by transgene expression is viewed as an important evidence for the existence of a PCD pathway in plants. The study of lesion mimic transgenes is important to our understanding of PCD and the signals that control it in plants. PCD-inducing transgenes may provide clues regarding the different entry points into the cell death pathway, the relationships between the different branches of the pathway (e.g., developmental or environmental), or the different mechanisms involved in its induction or execution. Cell death-inducing transgenes may also be useful in biotechnology. Some lesion mimic transgenes were found to be induced in plants a state of systemic acquired resistance (SAR). These genes can be used in the development of pathogen-resistant crops. Other cell death-inducing transgenes may be used as specific cell ablation tools. Although mainly revealed unintentionally, and at times considered 'an adverse phenotype', lesion mimic transgenes should not be ignored because they may prove valuable for studying PCD as well as developing useful traits in different plants and crops. PMID- 11199393 TI - Ozone: a tool for probing programmed cell death in plants. PMID- 11199394 TI - Programmed cell death in cell cultures. AB - In plants most instances of programmed cell death (PCD) occur in a number of related, or neighbouring, cells in specific tissues. However, recent research with plant cell cultures has demonstrated that PCD can be induced in single cells. The uniformity, accessibility and reduced complexity of cell cultures make them ideal research tools to investigate the regulation of PCD in plants. PCD has now been induced in cell cultures from a wide range of species including many of the so-called model species. We will discuss the establishment of cell cultures, the fractionation of single cells and isolation of protoplasts, and consider the characteristic features of PCD in cultured cells. We will review the wide range of methods to induce cell death in cell cultures ranging from abiotic stress, absence of survival signals, manipulation of signal pathway intermediates, through the induction of defence-related PCD and developmentally induced cell death. PMID- 11199395 TI - Regulators of cell death in disease resistance. AB - Cell death and disease resistance are intimately connected in plants. Plant disease resistance genes (R genes) are key components in pathogen perception and have a potential to activate cell death pathways. Analysis of R proteins suggests common molecular mechanisms for pathogen recognition and signal emission whereas the subsequent signalling unexpectedly involves a network of pathways of parallel, branching and converging action. Disease resistance signalling mutants have revealed novel types of regulatory proteins whose biochemical functions are still unknown. Accumulation of small molecules such as salicylic acid, reactive oxygen intermediates, and nitric oxide amplifies resistance responses and directs cells to initiate cell death programs. Genetic analyses of lesion mimic mutants provide a glimpse of how cell death thresholds are set via an interplay of positive and negative regulatory components. PMID- 11199396 TI - Endonucleases. AB - Programmed cell death (PCD) involves hydrolysis of genomic DNA, which must be catalyzed by endonuclease(s) capable of digesting dsDNA. Plants have two major classes of endonucleases active towards dsDNA, Zn2+-dependent endonuclease and Ca2+-dependent endonuclease. Both classes are found among endonucleases nominated for machineries of PCD in plants. Survey of plant endonucleases in relation to PCD leads to a possibility that a different class of endonuclease reflects a different phase of PCD-associated DNA hydrolysis. PMID- 11199398 TI - Caspase-like protease involvement in the control of plant cell death. AB - Cell death as a highly regulated process has now been recognized to be an important, if not essential, pathway that is ubiquitous in all multicellular eukaryotes. In addition to playing key roles in the morphogenesis and sculpting of the organs to give rise to highly specialized forms and shapes, cell death also participates in the programmed creation of specialized cell types for essential functions such as the selection of B cells in the immune system of mammals and the formation of tracheids in the xylem of vascular plants. Studies of apoptosis, the most well-characterized form of animal programmed cell death, have culminated in the identification of a central tripartite death switch the enzymatic component of which is a conserved family of cysteine proteases called caspases. Studies in invertebrates and other animal models suggest that caspases are conserved regulators of apoptotic cell death in all metazoans. In plant systems, the identities of the main executioners that orchestrate cell death remain elusive. Recent evidence from inhibitor studies and biochemical approaches suggests that caspase-like proteases may also be involved in cell death control in higher plants. Furthermore, the mitochondrion and reactive oxygen species may well constitute a common pathway for cell death activation in both animal and plant cells. Cloning of plant caspase-like proteases and elucidation of the mechanisms through which mitochondria may regulate cell death in both systems should shed light on the evolution of cell death control in eukaryotes and may help to identify essential components that are highly conserved in eukaryotes. PMID- 11199400 TI - Cell death: the 'Yin' path in the balancing act of the life cycle. PMID- 11199397 TI - Plant proteolytic enzymes: possible roles during programmed cell death. AB - Proteolytic enzymes are known to be associated with developmentally programmed cell death during organ senescence and tracheary element differentiation. Recent evidence also links proteinases with some types of pathogen- and stress-induced cell suicide. The precise roles of proteinases in these and other plant programmed cell death processes are not understood, however. To provide a framework for consideration of the importance of proteinases during plant cell suicide, characteristics of the best-known proteinases from plants including subtilisin-type and papain-type enzymes, phytepsins, metalloproteinases and the 26S proteasome are summarized. Examples of serine, cysteine, aspartic, metallo- and threonine proteinases linked to animal programmed cell death are cited and the potential for plant proteinases to act as mediators of signal transduction and as effectors of programmed cell death is discussed. PMID- 11199399 TI - Salicylic acid in the machinery of hypersensitive cell death and disease resistance. AB - Although extensive data has described the key role of salicylic acid (SA) in signaling pathogen-induced disease resistance, its function in physiological processes related to cell death is still poorly understood. Recent studies have explored the requirement of SA for mounting the hypersensitive response (HR) against an invading pathogen, where a particular cell death process is activated at the site of attempted infection causing a confined lesion. Biochemical data suggest that SA potentiates the signal pathway for HR by affecting an early phosphorylation-sensitive step preceding the generation of pro-death signals, including those derived from the oxidative burst. Accordingly, the epistatic relationship between cell death and SA accumulation, analyzed in crosses between lesion-mimic mutants (spontaneous lesion formation) and the transgenic nahG line (depleted in SA) places the SA activity in a feedback loop downstream and upstream of cell death. Exciting advances have been made in the identification of cellular protective functions and cell death suppressors that might operate in HR. Moreover, the spatio-temporal patterns of the SA accumulation (non homogeneous distribution, biphasic kinetics) described in some HR lesions, may also reveal important clues for unraveling the complex cellular network that tightly balances pro- and anti-death functions in the hypersensitive cell death. PMID- 11199401 TI - [Snowboarding accidents]. AB - The present review summarises the related literature of the last ten years with request to snowboarding accidents. Sport accident statistics of snowboarding show high and increasing numbers of injuries. Already snowboarding ranks third of all sport accidents in Switzerland. According to the literature the injury risk in snowboarding is twice that of skiing, although the injuries are less serious. About 50% of the injured snowboarders are beginners. Beginners have a higher risk of injury than more advanced snowboarders. Additionally, and a relative large part of them are injured the first day of their snowboard career. The pattern of injury has changed over the last years. Today, injuries to the lower extremities account no longer for more than 50% but are now decreased to about 25%. Nowadays, wrist, knee, ankle, and shoulder are the most frequently injured body parts. It is the authors opinion that with up-to-date protectors, release bindings, and training of falling techniques the numbers and seriousness of injuries could be reduced, in particular injuries to the wrist and ankle. PMID- 11199402 TI - [Injuries and overuse syndromes due to rock climbing on artificial walls]. AB - The purpose of this study was to obtain an overview of acute injuries and chronic overuse syndromes due to rock climbing on artificial climbing walls. Strategies for prevention should then be developed based on these experiences. From October 1995 to December 1996 314 climbers of both sexes and all degrees of climbing abilities were individually interviewed at five different indoor climbing arenas with the help of a special questionnaire. Type, quantity and cause of typical injuries and overuse syndromes on artificial climbing walls were determined. Injuries (n = 204) as well as overuse syndromes (n = 266) increased with the performance level. Experienced climbers often suffered from injuries to the finger flexor tendons (n = 42) and the finger flexor pulleys (n = 37) while holding small grips. Beginners sustained skin injuries (n = 26) and joint distortions (n = 22) of the lower limb while falling. Reasons are a lack of experience in the techniques of belaying and falling as well as incomplete covering of the ground with crash mats. Chronic overuse syndromes mainly presented as swelling and pain in the finger joints (n = 140) and as epicondylitis in the elbow (n = 30). Especially knee problems (n = 12) were caused by new climbing techniques used on artificial climbing walls. Referring to injuries as well as to overuse syndromes climbing on artificial climbing walls is a very safe sport, compared to climbing on natural rock. Further prevention could be provided by a well-based instruction of beginners, especially in techniques of belaying and falling. The ground of climbing walls should always be completely covered by sufficient crash mats. More experienced climbers should minimize harmful climbing techniques, like using very small holds with a cling grip, long distance reaches and inside rotation of the leg under pressure. PMID- 11199403 TI - [Plantar pressure distribution in inline skating on straights]. AB - Plantar pressure distribution in inline skating on straight was measured with a flexible insole in 13 experienced subjects at a speed of 18 and 24 km/h. The results showed three areas that were exposed to high pressures, i.e. the heel with 258 and 265 kPa, the first metatarsal head with 265 and 281 kPa, the hallux with 319 and 324 kPa at 18 and 24 km/h, respectively. All other areas showed peak pressures that were less than half of these values. Lowest values were found in the midfoot area. Changing speed from 18 to 24 km/h led to a small increase of peak pressures in all areas. Peak pressures were comparable to walking but showed the trend to be lower than in running. PMID- 11199404 TI - [Incidence of dental, mouth, and jaw injuries and the efficacy of mouthguards in top ranking athletes]. AB - The aim of the study was to determine the prevalence of orofacial injuries among German top athletes and their attitudes to mouthguards. A questionnaire was mailed to athletes of 10 German contact sports associations. 64.3 percent (303) of the athletes returned questionnaires. 62 percent (188) of the respondents reported that at some time they wore a mouthguard for sports participation. 47.3% (male: 57.8%, female: 38.3%) of these were currently using one. 50% of the mouthguards were custom made by dentists, and 50% were shop bought (boil-and bite). 32 percent of the participants had, at some time during their sports career, suffered an orofacial injury. The incidence of fractured anterior upper teeth and completely knocked out teeth for athletes without mouthguards was 7 and 14, respectively. Whereas for athletes wearing mouthguards one fractured tooth was reported. Athletes with mouthguards complained of problems with speaking (19.9%) rather than of breathing (3.4%) and fitting difficulties (4.8%). Boil-and bite mouthguards caused more fitting problems than custom-made ones. As prevalence of oral injuries in body-contact sports is high, athletes should be advised that custom-made mouthguards offer the greatest comfort, fit, durability, and protection against dental injuries. PMID- 11199405 TI - [Diagnosis and therapeutic management following traumatic anterior shoulder dislocation according to extrinsic prognostic factors]. AB - We examined the importance of preoperative CT- and NMR-imaging concerning the detection of a bankart-lesion by a retrospective evaluation of 36 patients with primary traumatic or posttraumatic recurrent shoulder dislocations. Because of unfavourable extrinsic prognostic factors, we advised shoulder arthroscopy and surgical stabilization in all cases. Intraoperatively 35 of 36 patients (97%) presented a bankart-lesion. Preoperatively a bankart-lesion was detected in 32 cases (91%) by CT (n = 29) or NMR (n = 7). We could predict the probability of a bankart-lesion with a high reliability by clinical evaluation alone due to several risk-factors. All patients had at least 2 unfavourable prognostic factors. Under these circumstances we could assume a bankart-lesion with a probability of 97%. Therefore in our opinion preoperative CT or NMR is not advised as standard diagnostic procedure in patients with high-risk of recurrence according to extrinsic prognostic factors. We recommend preoperative CT or NMR when the estimation of prognostic factors concerning the risk of redislocation is doubtful and in case of difficult clinical and ultrasound examination regarding shoulder laxity or rotator cuff lesions. PMID- 11199406 TI - [N. thoracicus longus lesion--a rare injury in weight lifting]. AB - The case of long thoracic mononeuropathy associated with sport participation a presented. The diagnosis was confirmed with electromyography. It is suggested that the athletic activity caused a stretch injury to the long thoracic nerve. Degenerative changes and infections were excluded. Conservative management, consisting of range of motion exercises for the shoulder and strengthening of the serratus anterior muscle, resulted in a forable outcome. The 12 month follow-up showed only slight changes in EMG and clinical examination. PMID- 11199407 TI - [Documentation in sport physiotherapy]. PMID- 11199408 TI - [Orthopedics 2000. Address by the President of the German Society of Orthopedics and Traumatology]. PMID- 11199409 TI - [Diagnosis of rotator cuff rupture: correlation of clinical findings and magnetic resonance tomography with intraoperative findings]. AB - The diagnosis of rotator cuff tears may be based on clinical examination and MRI. The aim of this study was to define the relative value of these methods. Clinical and MRI diagnoses of 88 shoulders were compared with the intraoperative findings. The correct diagnosis of a posterosuperior rotator cuff rupture was made in 79% of the cases by clinical examination and in 91% of the cases by MRI. For the subscapularis tendon clinical examination corresponded to the intraoperative findings in 73% of the cases versus 59% for MRI. MRI was superior to clinical examination in diagnosing a posterosuperior rotator cuff rupture. For the evaluation of ruptures of the subscapularis tendon, clinical examination was more reliable than MRI. Diagnosis of rotator cuff rupture can most often be obtained by a simple physical examination. PMID- 11199410 TI - [MRI-based 3-D analysis of the glenohumeral translation in patients with shoulder instability]. AB - AIM: Until now, pathological translation of the glenohumeral joint could not be assessed three-dimensionally and in functionally important arm positions in the living. The objektive of this study was therefore to develop an MR-based technique for determining the three-dimensional glenohumeral translation in functionally relevant positions in vivo. METHOD: In an open MR scanner both shoulder joints of 5 volunteers with an unilateral traumatic instability were examined in different positions of abduction and rotation. After semiautomatic segmentation, 3D reconstruction of the bony structures of the shoulder girdle was performed and the center of mass of the glenoid cavity was determined and used as reference point. In a virtual reality, the midpoint of the humeral head was assessed and its position relative to the center of mass of the glenoid cavity was calculated. RESULTS: At 30 degrees of abduction, in both shoulders, the humeral head was positioned inferior and posterior relative to the glenoid cavity (healthy: 0.42 +/- 1.1 inf., 0.75 +/- 1.0 mm post.; unstable: 1.31 +/- 0.87 mm inf., 0.51 +/- 1.28 mm post.) The maximal translation (to anterior and inferior) was observed both on the healthy side (mean 1.0 mm, max. 1.8 mm) and in the unstable shoulders (mean 2.5 mm, max. 4.6 mm) with the arm in 90 degrees of abduction and external rotation, thus being 1.7 to 2.5 times higher in the pathological shoulders. CONCLUSIONS: With this technique the glenohumeral translation can be quantified three-dimensionally in functionally important positions and without projectional artefacts. In the future, this method can be applied to patients with different entities of shoulder instability. PMID- 11199411 TI - [Damage to the glenoid labrum and expert assessment]. AB - AIM: Development of criteria for the medical-legal interpretation of different patterns of labral lesions according to the labrum pathology and mechanism of injury. METHODS: A metaanalysis of the literature concerning injuries and diseases of the shoulder involving the glenoid labrum was performed. RESULTS: Lesions of the superior, anterior and posterior labrum are rare and of different severity. Arthroscopically they are divided into distinct types. They develop either spontaneously together with intraarticular diseases, due to chronic fatigue or by injury. In this field the stability of the shoulder joint and the tension of the long head of the biceps tendon play an important role. There is no correlation between the type of lesion and mechanism of injury. With respect to medical-legal interpretation, the currently used classification of labral lesions is not very helpful or is even confusing. We therefore propose a new classification according to the meniscus pathology which shows a striking similarity to labral pathology. There are two types of labral lesions: Type one shows degenerative defects, which may be influenced by mechanical loading; type two follows from shoulder instability. CONCLUSIONS: Medical-legal interpretation of labral lesions should follow the same principles that were shown to be useful in knee joint instability and meniscal tears. Only traumatic luxations of the shoulder joint may lead to labral tears without any other alterations. PMID- 11199412 TI - [Effectiveness of epicondylitis bandages from the biomechanical viewpoint--an experimental study]. AB - QUESTIONS: During extension of the elbow joint (test measurement) and extension of the wrist (control measurement), maximal bandage pressure is desired on the extensor group of the forearm, especially of the M. extensor carpl radialis brevis (ECRB). Do the various commercial epicondylitis bandages produce a mechanical effect on the extensor group of the forearm and how do the maximal pressures of these bandages behave in direct comparison? Are the pressures produced clinically relevant? METHODS: Eleven different epicondylitis bandage constructions were examined for their biomechanical effects. The exerted pressure was measured continously during the above-mentioned movements. A fist-closing strength of ca. 30 N was maintained for the necessary pre-stressing of the forearm muscles. RESULTS: Strap-type bandages were the only bandages to produce adequately high pressures. Bands applied at pressures which approach those of the straps led to obstruction in bloodflow. Stocking designs showed no effect in respect to our study. CONCLUSION: Bandages which apply pressure to relieve the tendon insertion of the extensor muscles must, from a technical standpoint, be of a strap construction in order to build up adequate pressures to be effective. PMID- 11199413 TI - [Is open synovectomy of the metacarpophalangeal joint in chronic polyarthritis worthwhile?]. AB - PURPOSE/METHODS/PATIENTS: This work retrospectively analysed 252 synovectomies performed on 153 patients from 1958 to 1995 at the Balgrist University Orthopaedics Clinic, and evaluated the short-term and long-term benefits of open synovectomy of the metacarpo-phalangeal joint in rheumatoid arthritis. RESULTS: Rheumatoid arthritis (n = 182) was by far the most common of the 21 different diagnoses involved, and the metacarpo-phalangeal joint (n = 101) was by far the most frequently operated of the 7 different joint types in question. In the short tenn (n = 97), after a mean of 5.5 months, open synovectomy of a metacarpo phalangeal joint in rheumatoid arthritis patients provided a benefit in terms of mobility in 85% of cases and in terms of joint swelling and pain in 93% of cases. Among one-third of the originally operated cases (n = 38), long-term benefit, i.e. after a mean of 6.9 years, was obtained in 89% of cases with regard to joint mobility, 87% with regard to swelling and 97% with regard to pain relief. Two thirds of the joints presented normal mobility and swelling, and three-quarters were pain-free. CONCLUSIONS: The metacarpo-phalangeal joint is very important for maintaining the independence of a patient (gripping). Open synovectomy of the metacarpo-phalangeal joint in rheumatoid arthritis patients is an effective therapeutic procedure with little morbidity and very good long-term benefit in the management of metacarpo-phalangeal pain, swelling and stiffness refractory to conservative therapy. PMID- 11199414 TI - [Surgical shortening of the Achilles tendon for correction of elongation following healed conservatively treated Achilles tendon rupture]. AB - INTRODUCTION: Is operative shortening of the achilles tendon an adequate therapy in cases of elongation following conservative treatment of achilles tendon rupture? METHODS: From 11/89 to 12/97, 12 patients underwent achilles tendon shortening (9 male, 3 female, average age 43 years). All patients had an elongated tendon following conservative treatment of achilles tendon rupture. We were able to examine 8 patients (67%) after the operation. The average follow-up period was 35 (7-103) months with an average span between the primary trauma and surgery of 22 (8-45) months. RESULTS: Prior to surgery, all patients complained of weakness, gait disturbance and limitation of activity. At follow-up a subjective weakness of the plantar flexion remained in five and an objective weakness in all patients. We found a decrease of the isometric plantar flexion strength to 52% of the non-operated lower extremity while the maximum calf circumference was only 5% decreased. Only two patients reported of a gait disturbance and activity limitation whereas three patients were free of complaints. Using a modified Trillat score (1,967), 7 patients rated good or very good (1 poor). CONCLUSIONS: Achilles tendon shortening in case of elongation following conservative treatment of achilles tendon rupture helps to decrease gait disturbance and limitation of activity whereas a lack of the isometric plantar flexion strength persists. In our opinion an early decision for achilles tendon shortening might prevent this deficit. PMID- 11199415 TI - [Bursitis tendinis calcanei in extensive calcaneus erosion]. AB - INTRODUCTION: Mechanical and static stress as well as rheumatic diseases may cause retrocalcanear bursitis. Anatomic variants of the calcaneus predispose to this bursitis. CASE: A 51-year-old woman being afraid of operation waited 2 years before undergoing bursectomy al her right heel. For this reason the increase of calcanear bone loss and its stabilisation by sclerosis is well documented in X rays and MR images. A secondary synovialitis of the peroneal tendons decided completely after bursectomy. No signs of rheumatic disease were found. CONCLUSION: The radiological, clinical and hisiological findings in long persisting bursitis are often simular to those found in patients with rheumatic disease. Normal laboratory findings do not preclude an early stadium of rheumatic disease. For this reason, these patients had to be instructed to return if they develop further synovialitis to verify the diagnosis and to avoid delayed therapy. PMID- 11199416 TI - [Early results of a prospective study in patients with computer-assisted femur shaft preparation in total hip endoprosthesis implantation (Robodoc system)- indications, outcome, complications]. AB - AIM: Indications, results, advantages and disadvantages of the computer-guided femoral preparation in total hip arthroplasty (Robodoc) in our patients are recorded and represented. METHOD: 41 patients who underwent a computer-guided femoral preparation in total hip arthroplasty (Robodoc) were examined after 1 year on average in a prospective study. The evaluation was made using the Harris Hip Score. The advantages and disadvantages of the Robodoc-assisted surgery are described. RESULTS: More than 80% of the patients had a good or very good result (> 80 points of Harris Hip Score) 3 month after surgery; after 6 months in 20 of 21 patients a score of more than 85 pts. was calculated. The following complications were noticed: thrombotic embolism (2) with one lethal embolism included, fracture of the greater trochanter using the straight stem (3), aseptic drainage due to hematoma (2). 12 patients noticed a postoperative pain at the distal marking pin location (condylus femoris medialis) for an average of 3 months. CONCLUSION: Generally, Robodoc-assisted surgery may be performed in all uncemented total hip arthroplasties. The individual indication should be checked because of the increased effort of surgery, the advantages and disadvantages, and the non-proven better long-term results in comparison to the regular technique. It seems that the Robodoc system provides advantages in post-traumatic arthritis and deformities of the proximal femur (varus and valgus neck) on account of the computer-aided preoperative planning and correct operative realization. PMID- 11199417 TI - [Computer-assisted navigated acetabulum placement in hip prosthesis implantation- application study in routine clinical care]. AB - AIM: This study serves to examine the feasibility of a CAS system in clinical routine use in the field of total hip replacement. METHOD: Within a prospective study 70 total hip replacements were performed by one surgeon (KB) between March and November, 1999 using a CAS system for preoperative planning and intraoperative cup placement. RESULTS: The average operating time was 70 min. This means an average increase in total time of operation about 15-20 min. The average blood loss was 630 ml. No additional specific complications due to the use of the system were seen. There was no additional trauma created by percutaneous pointing at the spina or flxing a dynamic reference base (DRB) at the pelvis. CONCLUSION: The active application of this CAS system in clinical routine use showed very good results in feasibility and can be considered as reliable. The navigated cup placement shows the potential of improving the results in cup placement, thus improving the outcome of hip arthroplasty. PMID- 11199418 TI - [Polyethylene content and cell size of foreign body giant cells in aseptic hip prosthesis loosening--a histomorphometric study]. AB - INTRODUCTION: In aseptic loosening of cementless hip arthroplasty polyethylene particles are phagocytized by macrophages and foreign-body giant cells. This initiates an osteolytic cascade. In this study, the authors investigated if there are correlations between the size of foreign-body giant cells and the polyethylene loading and number of intracellular particles as determined by light microscopy. MATERIAL AND METHOD: Histological specimens were processed from tissues retrieved during revision surgery of 7 cases of cementless hip arthroplasty which had become aseptically loose. The specimens were analyzed by histolomorphology and histomorphometry. The cell size, polyethylene loading and intracellular particle number of 111 foreign-body giant cells were determined. A regression analysis was performed to investigate if there was a correlation between these variables. RESULTS: The mean cell size was 1417 +/- 487 micron 2, the mean polyethylene loading was 49 +/- 42 micron 2 and the mean intracellular particle number was 10.4 +/- 5.4. The cell size correlated with both the intracellular particle number (r = 0.25) and the polyethylene loading (r = 0.39). CONCLUSIONS: In the cellular reaction to polyethylene particles in aseptic loosening of cementless total hip arthroplasty, the size of foreign-body giant cells correlates with intracellular polyethylene loading and intracellular polyethylene particle number as determined by light microscopy. The presence of large foreign body giant cells might be associated with a high particle load of the tissue and a high osteolytic activity. PMID- 11199419 TI - [Evaluating rehabilitation progress by measuring thigh circumference]. AB - QUESTION: Thigh girth measurements have been widely used to quantify rehabilitation progress following knee surgery, but the correlation between thigh girth and other functional measures has not been investigated. This study intended to investigate whether such a correlation exists. METHODS: 15 women with bilateral osteoarthrosis of the knee participated in this study. Isokinetic knee extensor strength, thigh girth and body mass were measured immediately before, then at six weeks and six months following cementless total knee arthroplasty. RESULTS: The involved side showed clear pre-operative isokinetic knee extensor strength deficits, and slight reductions in thigh girth. Post-operatively, mean strength deficits were reduced, whereas differences in mean thigh girth became lager. Although thigh girth changes correlated well with body mass, they did not correlate with knee extensor strength. CONCLUSION: Changes in thigh girth are mainly due to changes in body mass. Thigh girth measurement is of no use for the quantification of the rehabilitation progress in total knee arthroplasty. PMID- 11199420 TI - [Chronic recurrent multifocal osteomyelitis]. AB - The aim of this paper is to give a detailed description of the so-called "chronic recurrent multifocal osteomyelitis" (CRMO). The clinical, radiological and histopathological results of an analysis of 29 cases (15 children/adolescents and 14 adults) are presented and correlated to current data from the literature. We could delinate the following points: 1. CRMO is a systemic aseptic inflammation of the bone marrow (Osteitis), it can occur polytopically and association with pustulous dermatologic symptoms is possible. 2. It is not a rare disease 3. Osteomyelitis is probably "reactive" and a plasma-cell sclerotic process with ist own characteristic histologic three-phase course. 4. We could observe 5 specific types of localization which can be documented by X-ray or bone scan. 5. Accompanying arthritis os often present, especially "sympathetic coxitis". 6. The use of drugs in treatment of CRMO (i.e. azithromycin, calcitonin, and bisphosphonates) is discussed. In conclusion we want to point out, that 1. 99mTC bone scan should always be performed when there is suspicion for CRMO to reveal the pattern of affection, 2. the rheumatologist and dermatologist should be contacted, 3. operation is normally not necessary for treatment of the mostly self-limitin disease, and 4. the term "SAPHO syndrome" should be avoided, further differentiation of the diagnosis is necessary. PMID- 11199421 TI - [Osseontegration of trial implants of carbon fiber reinforced plastics]. AB - PROBLEM: To what extent are carbon fibre-reinforced plastics (CFRP) suitable as an osseous integration surface for implants? METHOD: CFRP test implants having a plexus-structured, rhombus-structured, and plexus-structured, hydroxyapatite surface were implanted in the femura of mini-plgs. Exposure time lasted 12 weeks. The implants were subjected to a macroradiological, a histological histomorphometrical, and a fluorescence-microscopical evaluation. RESULTS: One half of the uncoated, plexus-structured implants were not osteointegrated, the other half displayed an osteointegration rate of 11.8% in the spongy area and 29.8% in the cortex layer. The HA-coated test implants showed an osteointegration of 29.5% in the spongiosa and 56.8% in the cortex layer. The rhombus-structured test implants had an osteointegration of 29.2% (spongiosa) and 46.2% (cortex layer). CONCLUSION: Compared to the osteointegration of metallic, especially titanium surfaces the CFRP surfaces tested by us fared worse, especially the uncoated, plexus-structured surfaces. For this reason we view very critically the use of carbon-fibre reinforced plastics together with the surfaces tested by us as osteointegrating surfaces. PMID- 11199422 TI - [Arterial complications caused by using an axillary crutch]. AB - BACKGROUND: Of all upper extremity emboli, up to twenty percent arise from an arterial, not a cardiac source. METHOD: We report about a patient with recurrent embolism, caused by an axillary crutch-induced aneurysm of the axillary artery. RESULT: After revascularisation by embolectomy and axillo-brachial vein graft bypass, the patient was free of symptoms. CONCLUSION: Angiography and duplex scanning were necessary for the correct diagnosis. PMID- 11199423 TI - [Transplantation of osteochondral cylinders in various joints--technique and initial results]. PMID- 11199424 TI - [Role of HLA-B27 in Bechterew disease]. PMID- 11199425 TI - [Changes in muscle strength after implantation of knee joint endoprostheses]. PMID- 11199426 TI - [Small intestinal transit with radio-opaque markers to localize intermittent small bowel obstruction] . AB - AIM: In difficult diagnostic cases of partial small bowel obstruction, radiopaque, non-digestible markers were used to challenge and localize the site of obstruction. MATERIAL AND METHOD: 32 patients (19 female, 13 male, 3-80 years) were examined. Each patient received 20 4-mm radiopaque markers orally. Abdominal radiographs were obtained at 4-8 h intervals. Mechanical obstruction was defined as the clustering of at least 3 markers for 4 hours or longer. The transit of radiopaque markers was compared to plain radiography, ultrasound, barium meal, computed tomography, enteroclysis and operative findings. RESULTS: 18 of 32 patients showed small bowel clustering suggestive of obstruction. Diagnostic agreement was found in 12 of 14 cases with ultrasound, in 7 of 13 cases with plain radiography and in 3 of 6 cases with enteroclysis. 13 of the 18 patients with clustering had surgery. All of them (13/13) had adhesions with the need of resection. CONCLUSION: This investigation is an alternative diagnostic method for the decision between conservative and surgical treatment in cases of intermittent partial small bowel obstruction. PMID- 11199427 TI - [Tissue harmonic imaging sonography. Is the image quality in routine abdominal ulstrasound improved?]. AB - PURPOSE: Evaluation and statistical analysis of the influence of THI with pulse inversion technology on image quality in abdominal ultrasound in comparison to conventional sonography. MATERIAL AND METHODS: In 25 patients 398 ultrasound images of the abdomen were evaluated in a prospective, double blind study. 49% of the images were obtained with THI sonography, 51% with conventional sonography, respectively. Image parameter, anatomical region and image plane were kept constant by using a switchable ultrasound probe. Image contrast, delineation of organs, detection of vessels and artifacts in cystic structures were evaluated by four radiologists using a 3-grade scale. The interobserver variability was determined. RESULTS: The results of all groups showed statistically significant improvement compared to conventional sonography. High agreement of the evaluaters was achieved for image contrast and delineation of organs, less agreement in detection of vessels and artifacts in cystic structures, respectively. CONCLUSION: Image contrast and delineation of organs to neighboring structures as well as reduction of artifacts in cystic structures and vessels are statistically significantly improved with THI sonography using pulse-inversion technology in comparison to conventional sonography. PMID- 11199428 TI - [Papillary renal cell carcinoma: comparison of CT and gross morphology]. AB - OBJECTIVE: To analyze the CT appearance of papillary renal cell tumor (pRCT) under consideration of gross pathology. MATERIAL AND METHODS: Preoperative CT scans of 10 patients suffering from pRCT were re-evaluated by two experienced radiologists. CT appearance was correlated to gross morphology. RESULTS: On CT, 9/10 tumors were depicted as rounded, well circumscribed and sharply delineated masses. These tumors presented a hypodense central area correlating to necrosis in gross pathology. The central area of necrosis was surrounded by vital tumor tissue, presenting as a serpiginous, contrast-enhancing margin on CT. One tumor was polycyclic due to multiple tumor nodules, but sharply demarcated towards the surrounding renal tissue. CONCLUSIONS: pRCT presents a quite unique CT appearance similar to its gross pathology. PMID- 11199429 TI - [MRI of osteomyelitis: sensitivity and specificity of STIR sequences in comparison with contrast-enhaned T1 spin echo sequences]. AB - PURPOSE: To evaluate the need for additional MR sequences including administration of Gd-DTPA after inconspicuous Short-Tau Inversion-Recovery (STIR) sequence to exclude the diagnosis of osteomyelitis. MATERIAL AND METHODS: 112 MR examinations of 79 patients acquired for the detection of possible osteomyelitis were analyzed retrospectively. All examinations were performed at 0.5 T including STIR, T1-weighted spin echo sequences (T1 SE) before and after application of Gd DTPA. Additionally, 93 T2-weighted spin echo sequences were available. The examinations were analyzed by two experienced radiologists. First, the STIR sequences were studied, followed by the T1 SE images before and after administration of contrast material. Finally, the T2-weighted images were evaluated. Diagnoses were confirmed by operation (22), biopsy (10), and follow-up (80). RESULTS: In 53 cases osteomyelitis was diagnosed, while the remaining 59 cases suffered from another disease. The sensitivity of the STIR sequence was 100% while the specificity for osteomyelitis was 49.2%. The specificity increased to 79.7% by including T1 SE images into the analysis and reached 83.1% after considering the contrast enhanced images. T2-weighted images yielded no additional information. CONCLUSION: The combination of STIR and T1SE images shows a high sensitivity and specificity for osteomyelitis, thus obviating the need for any additional examinations. PMID- 11199430 TI - [CT-guided percutaneous intratumoral chemotherapy with a novel cisplatin/epinephrine injectable gel for the treatment of inoperable malignant liver tumors]. AB - PURPOSE: To evaluate prospectively the volumetric changes of tumor and necrosis in unresectable malignant liver tumors and the clinical aspects after CT-guided direct intratumoral administration of a novel cisplatin/epinephrine injectable gel in a clinical phase II study. PATIENTS AND METHODS: 8 patients with 17 colorectal liver metastases with a mean volume of 42 ml were treated with a mean of 5.1 injections and 8 patients with 11 HCC nodules (mean volume of 22.1 ml) with a mean of 3.25 treatments with CT-guided local administration of a novel cisplatin/epinephrine gel. This method of administration provides a higher local and lower systemic drug concentration. Volumes of tumor and necrosis prior to and after treatment were measured by computer-generated volumetric analysis. RESULTS: Contrast-enhanced studies verified pretherapeutic tumor necrosis with a value of 12.6% in the metastases and 0.6% in the HCC nodules. Intratumoral drug administration resulted in a necrotic volume of 110% in metastases and 128% in HCC versus the mean initial tumor volume, at least 4 treatments resulted in 122% necrosis in metastases and 130% in HCC. Local therapy control rate for the follow up to 6 months was 38% and 83.3% for the group of metastases and HCC, respectively. CONCLUSIONS: Direct intratumoral injection of a novel cisplatin/epinephrine injectable gel results in an induction of a relevant necrosis in malignant liver tumors, with a substantially higher local therapy control rate for HCC compared to colorectal metastases. PMID- 11199431 TI - [Low-dose thrombolysis using rt-Pa in extensive peripheral vascular occlusion]. AB - PURPOSE: To evaluate the efficacy of intra-arterial thrombolysis by rt-PA in acute and subacute extensive peripheral vascular occlusion. MATERIAL AND METHODS: 100 patients with acute and subacute occlusion of peripheral arteries were treated by catheter thrombolysis using 20 mg of rt-PA over a period of 20-24 hours. In all cases the occlusion extended to more than 20 cm and two stages of the extremity were involved. In 80 patients the original vessels (69/80 by thrombosis, 11/80 by embolization) and in 20 cases the femoro-popliteal bypass vessel was occluded. A catheter was inserted into the thrombus into which rt-PA and heparin were separately infused by two injectors. Heparin was given in a dose of 800-1000 U/h depending on the continuously monitored PTT levels. A control angiography was performed after 10 mg of rt-PA. After successful thrombolysis either PTA or aspiration thrombectomy was performed, if necessary, to reestablish a nearly normal vascular lumen. Open arteries of the thigh and at least one main vessel of lower leg was considered as success. RESULTS: Recanalization of the original vessels was successfully by thrombolysis, PTA or aspiration thrombectomy in 68/80 [85%] cases. Thrombolysis and PTA reestablished a normal lumen of the bypass vessel in 11/20 [65%] and in 6 more cases a recanalization with minor stenosis. In 13/15 patients with critical ischemia, thrombolysis probably helped to avoid amputation by reopening smaller collateral arteries. Bleeding at the puncture site, as a complication of thrombolysis, was the reason for stopping therapy in three cases. There was no retroperitoneal or cerebral bleeding. After successful thrombolysis, reocclusion occurred in 15 patients within one year, only in five cases amputation was necessary. CONCLUSION: Extensive occlusion of peripheral arteries or of a femoro-cural bypass can be successfully treated by low dose rt-PA thrombolysis with a low complication rate. Even partial reopening may prevent amputation. PMID- 11199432 TI - [The sacral perineural system--are there radiological criteria for an indication for surgery? First results and literature survey]. AB - PURPOSE: To establish recommendations for diagnostic imaging of cystic lesions of the sacral region and to evaluate for potential predictors of therapeutic outcome. METHODS: Conventional imaging of the lumbar spine, conventional CT, myelography, post myelo-CT and MRI were performed in 7 symptomatic [corrected] patients. All patients underwent operative decompression and histological examination. The radiographic examinations were reevaluated retrospectively and correlated with the postoperative outcome. RESULTS: In one patient the differential diagnosis of a neurinoma could not be excluded with CT and CT myelography alone. In all 7 patients MRI provided a definite diagnosis and a precise presentation of the cyst extension. A complete postoperative remission of symptoms was noticed in 4, a partial remission in three cases. The correlation of cyst extension, cyst shape, and the communication with the subarachnoid space did not provide predictive information concerning operative outcome. CONCLUSION: MR can be used as the sole imaging tool for demonstration of cystic lesions. Relevant disadvantages in comparison to myelography and myelo-CT were not evident. No imaging modality could predict the value of surgical intervention. PMID- 11199433 TI - [Quantification of fluid flow in magnetic resonance tomography: an experimental study of a flow model and liquid flow measurements in the cerebral aqueduct in volunteers]. AB - PURPOSE: To study the feasibility o MRI for quantification of fluid flow in a tube model and the cerebral aqueduct (CA) in volunteers. VOLUNTEERS AND METHODS: All studies were performed on a 1.5 T MR scanner using a head coil and a FLASH 2D phase contrast sequence with a velocity encoding at 20 cm/s. Flow (real value, ml/sec) of a saline fluid was measured in a flexible tube model with different inside diameters: 0.75-3 mm. Three flow velocities were given (normal value). To test the reproducibility, three studies were done using a flow of 0.12 or 0.14 ml/sec and a tube diameter of 0.75 and 2.0 mm. The ratio of normal to real flow value was calculated (ideal ratio = 1). MRI of CA and flow quantification was done in 24 volunteers (28 +/- 4 years). RESULTS: Using tubes with a diameter of 0.75 and 1.5 mm the real flow was sometimes higher than the velocity encoding of the phase contrast sequences. Because of this measurements of the fluid flow and the flow velocities were impossible. There was agreement for fluid flow quantification in the tube of 3.0 mm and high agreement in the tube of 2.0 mm in diameter with reproducible results. The mean diameter of the CA in normal subjects was 2.0 +/- 0.3 mm, the mean cerebral flow was 0.04 +/- 0.02 ml/sec and the peak velocity 3.06 +/- 1.59 cm/sec. CONCLUSIONS: Reliable flow quantification with MRI is feasible if the diameter of the lumen is greater than 1.5 mm, and if the flow velocity is lower than the velocity encoding. In cases of smaller diameters and higher flow velocities the velocity encoding has to be changed. Because of this the quantification seems to be inaccurate in cases of aqueductal stenosis with the method we used. PMID- 11199434 TI - [Full-field digital mammography: dose-dependent detectability of breast lesions and microcalcinosis]. AB - OBJECTIVES: The study compares contrast-detail and microcalcification detectability of a full-field digital mammography (FFDM) to a state-of-the-art conventional screen-film mammography (SFM) by using different doses in the digital system. MATERIALS AND METHODS: The investigations were performed with an FFDM (Senographe 2000 D, GEMS) and an SFM system (Senographe DMR, GEMS) using a contrast-detail mammography phantom (CDMAM) and an anthropomorphic breast phantom with superimposed microcalcifications. The digital detector was exposed with standard dose of SFM and with a dose reduction of up to 75%. Contrast-detail curves and correct observation ratio (COR) were performed for the CDMAM phantom. ROC analysis with a confidence level ranging from 1 to 5 was done with the results of the anthropomorphic phantom. RESULTS: Digital mammography with the same dose revealed at least an equivalent or even higher detectability rate than conventional mammography, COR could be increased at about 10-25%. The ROC analysis yielded better results for the FFDM system. The same lesion detectability in digital mammography as in the conventional method was reached at a dose reduction of about 25%, concerning spot views even at higher reduction. Dose reduction in the anthropomorphic phantom resulted in a linear loss of detectability. The same detectability as in conventional mammography was reached, however, by a dose reduction of about 50%. CONCLUSION: The results suggest that FFDM is at least equivalent to or--as far as spot views are concerned--superior to conventional SFM concerning the detectability of simulated lesions. Thus, a potential of dose reduction is suggested. PMID- 11199435 TI - [Reduction of the radiation exposure of patients caused by selected interventional and angiographic procedures]. AB - PURPOSE: To reduce patient doses caused by selected interventional and angiographic procedures using the digital C-arm unit "Multiskop". MATERIALS AND METHODS: After a patient study done previously, physical measurements with test phantoms were carried out, and physical-technical parameters such as distance between focus and image intensifier, additional filtration, and radiation dose per image were optimised. Then, the dose-area product (DAP) and the fluoroscopic time were measured for 130 percutaneous transluminal angioplasties (PTA), 40 PTA with stent implantation, 61 embolisations, and 302 digital subtraction angiographies (DSA). In the case of 16 PTA, 9 embolisations, and 38 DSA the number of radiographs was determined, and the DAP was divided into two parts, fluoroscopy and radiography. The measuring values were compared with data of the patient study done previously. RESULTS: The median values of the DAP and the fluoroscopic time amounted to 25 Gy cm2 and 9.7 min for PTA, 97 Gy cm2 and 8.5 min for PTA with stent implantation, 88 Gy cm2 and 17.2 min for embolisation as well as 54 Gy cm2 and 2.8 min for DSA. For the relation between DAP caused by fluoroscopy and radiography, and the number of radiographs, median values of 0.76 and 63 for PTA, 0.81 and 123 for embolisation as well as 1.85 and 134 for DSA were determined. In comparison to the patient study done previously the median values of the DAP were reduced by 31% for PTA, 26% for PTA with stent implantation, 55% for embolisation, and 38% for DSA. CONCLUSIONS: The comparison between the patient studies done previously and recently indicates the great potential of dose reduction for interventional and angiographic procedures. Although the X-ray equipment is ten years old the patient dose can be reduced by organizational and physical-technical modifications to such an extent that preliminary national reference dose values will not be exceeded. For further significant dose reductions while maintaining adequate image quality it will be necessary to purchase a modern X-ray equipment with pulsed fluoroscopy and automatic filter selection. PMID- 11199436 TI - [A review of molecular radiology. I: Gene therapy]. AB - The term molecular radiology intermediate region between radiological imaging and interventional radiology on the one side and molecular biology on the other. In the field of imaging methods are currently being developed by which molecular processes, i.e., gene expression and protein function, can be visualized in vivo. These techniques open new perspectives for research and clinical diagnosis and will be presented in the second part of this review. The present part provides a survey of current developments in gene therapy from a radiological point of view and highlights the part that our specialty may play in this field. PMID- 11199437 TI - [Full-field digital mammography]. AB - Due to the extremely high image quality requirements in mammography, there has for a long time been no adequate digital alternative to conventional film-screen mammography. The longest experience so far exists with digital mammography on the basis of storage phosphor (CR) systems. However, at normal dose this technique has a relatively poor signal-to-noise ratio and has not found general acceptance. Recently three novel systems for digital mammography by the companies Fischer (slot-scan detector), Trex (CCD-array), and GE (amorphous silicon detector) have been introduced and are currently under clinical investigation. The main advantage of digital mammography is the linear relationship between dose and detector signal with the possibility of a tailored optimization of image contrast. Other advantages include digital image storage, telemammography, and computer-assisted diagnosis. PMID- 11199438 TI - [Experimental studies on image quality in conventional film screen system, digital phosphor storage plate mammography in mangnification technique and digital mammography in CCD-technique]. AB - Comparison of image quality between conventional film screen system, digital phosphor storage plate mammography in magnification technique and digital mammography in CCD-technique. MATERIALS AND METHODS: Radiograms of a RMI mammography phantom were acquired using a conventional film screen system, two digital storage plate systems and two digital systems in CCD-technique. Additionally, the radiograms of one digital phosphor storage plate system were postprocessed emphasizing contrast and included in the comparison. RESULTS: The detectability of details was the best with the digital mammography in CCD technique in comparison with the conventional film screen technique resp. digital phosphor storage plate in magnification technique. CONCLUSIONS: Based on these results there is the possibility to replace the conventional film screen system by further studies--this has to be confirmed. PMID- 11199439 TI - [Intraoperative digital radiography for diagnosis of nonpalpable breast lesions]. AB - PURPOSE: A procedure for performing intraoperative digital radiography of diagnostic breast specimens directly in the operating suite with teleradiologic assessment by a radiologist is presented. The efficiency of this procedure is compared with that of conventional magnification mammography performed in the radiology department. MATERIAL AND METHODS: Thirty-six specimen radiographs obtained by conventional magnification mammography were compared with 38 intraoperative digital magnification radiographs (DIMA Soft P42 prototype, Feinfocus Inc., Garbsen). The radiographs were assessed for lesion conspicuity and time savings for the surgeon, anesthesiologist, and radiologist. RESULTS: The new procedure identified all 38 labeled pathological lesions, and the conventional technique likewise had a detection rate of 100% (36/36). The new technique resulted in considerable time savings for the surgeon and the radiologist. The duration of surgery was shorter and the time interval from removal of the specimen to reporting of the results was reduced from about 23 min to about 13 min. A single radiograph was sufficient for complete visualization of the specimen in all cases. CONCLUSION: Digital intraoperative specimen radiography considerably reduces the time of surgery depending on the local conditions and is highly accurate in locating a suspicious area within the tissue. PMID- 11199440 TI - [High resolution multislice CT of the lung: comparison with sequential HRCT slices]. AB - PURPOSE: To compare the image quality of high-resolution (HR) spiral CT scans from a multislice CT scanner with sequential HRCT scans from a singleslice CT scanner. MATERIALS AND METHODS: 20 patients with diffuse lung disease received a high-resolution spiral CT on a multislice scanner (4 slices) and 5 HRCT single slices (1 mm) on a singleslice scanner. Scan parameters of the multislice scanner were: Collimation 4 x 1 mm, pitch 6, slice thickness 1 mm. 5 HRCT slices were compared to the corresponding HR spiral CT slices using a 5-point scale by 5 radiologists with regard to the image quality and the number of artifacts. The evaluation was performed with a multivariate analysis (MANOVA test). RESULTS: Overall impression of image quality, noise, central vessels and bronchi, and all pathological changes were not significantly different between the two CT methods. Sequential HRCT scans were considered to be significantly better than HR spiral CT scans for spatial resolution (p = 0.02), depiction of peripheral vessels (p = 0.02), and of small bronchi (p = 0.05), and significantly worse for depiction of interlobar septa (p < 0.001). Diagnostically relevant differences were found in only 2.2%. Breathing and heartbeat artifacts each were 3 times higher in the sequential HRCT technique than in the multislice-spiral technique (p < 0.0001). CONCLUSION: HR spiral CT scans performed on a multislice CT scanner provide significantly less artifacts and an equal diagnostic image quality compared to sequential HRCT scans performed on a singleslice CT scanner. Multislice spiral CT in HR technique may replace the common scanning technique with conventional spiral CT and additional HRCT scans for diffuse lung diseases. PMID- 11199441 TI - [Contrast media-enhanced 3D MR angiography of peripheral arteries using an automatic tracking technique at 1.0 Tesla]. AB - PURPOSE: Assessment of the value of contrast-enhanced MR angiography (ceMRA) using an automatic tracking technique at 1.0 Tesla in comparison with digital subtraction angiography (DSA) of the pelvic and lower limb arteries. MATERIALS AND METHODS: In 15 patients with peripheral arterial occlusive disease a ceMRA (3D FLASH, TR/TE = 6.2/2.3 ms, Flip angle alpha = 30 degrees, Matrix 170 x 256) using a new automatic tracking technique was accomplished. The reference method was DSA. Twenty-one vessel segments of each patient were graded as normal, stenosed (> 50%) or occluded. Image material was evaluated independently by two radiologists. RESULTS: In comparison, the interobserver agreement showed a good (Cohen's kappa > 71%) concordance for 38% of the 21 vessel segments, a moderate (Cohen's kappa between 31%-70%) for 21% and a poor (Cohen's kappa < 30%) concordance for 38% of the 21 vessel segments. Regarding the MRA and DSA results, a good concordance was achieved for 62% of the 21 vessel segments, 14% showed a moderate concordance and 24% only a poor concordance. CONCLUSION: In patients with peripheral arterial occlusive disease ceMRA using an automatic tracking technique enables a reliable evaluation of pelvis and upper limb arteries at 1.0 Tesla. However, a reliable evaluation of lower limb arteries is not yet possible. PMID- 11199442 TI - [Contrast media-enhanced 3D MR angiography before endovascular treatment of aneurysm in the abdominal aorta, iliac artery and peripheral vessels]. AB - PURPOSE: The value of DSA for the measurement of aortic and peripheral arterial aneurysm dimensions before endovascular treatment is limited by projection effects. It was evaluated if additional gadolinium-enhanced three-dimensional MR angiography (3D-CEMRA) could compensate for the disadvantages of DSA. MATERIALS AND METHODS: 21 patients with 35 aneurysms in the abdominal aorta (14), iliac (9) and femoropopliteal vessels (12) were assessed with DSA (7 with calibrated catheter, 14 with yardstick) and 3D-CEMRA (TR/TE 7.8/2.1 ms, flip-angle 40 degrees, Matrix 512 x 224, FOV 500 mm, eff. slice 1.8 mm). We measured and compared aneurysm dimensions on both modalities. 3D-CEMRA was regarded as the reference method to evaluate the dimension of DSA-projection effects. RESULTS: Diameter and length of aneurysms were underestimated on DSA with the yardstick as reference. The deviation ranged from 15% (+/- 5%) in the aorta to 21% (+/- 10%) in the iliac vessels. Only with calibrated catheters as reference (7/21 DSA), were the distances on DSA correlated well with MRA. In 2/35 aneurysms 3D-CEMRA detected thrombosis with difference between length of inner lumen dilatation on DSA and whole aneurysm length. 2/5 accessory renal arteries found on DSA were not detected on 3D-CEMRA. CONCLUSIONS: 3D-CEMRA is a valuable adjunct to DSA for pre interventional diagnostics of aortic and peripheral arterial aneurysms. It provides exact evaluation of aneurysm dimensions and information about partial thrombosis. PMID- 11199443 TI - [Contrast media-enhanced MR angiography of the lower extremity arteries using a dedicated peripheral vascular coil system. First clinical results]. AB - PURPOSE: To evaluate contrast enhanced magnetic resonance angiography (ceMRA) of the pelvic and peripheral arteries with a dedicated peripheral vascular coil system and automated table-feed technique in patients with arterial occlusive disease. METHODS: Three-dimensional gadolinium-enhanced MR angiography in a two step automatic table feed technique was performed in 45 patients using a 1.5 Tesla imager (Magnetom Symphony, Siemens). The pelvic arteries were imaged with a single injection of contrast material. The upper and the lower leg were imaged with a second injection of contrast material in an automated table feed technique using a dedicated vascular coil system. In 20 patients ceMRA was compared with digital subtraction angiography (DSA) as the standard of reference and in 25 patients ceMRA was performed solely. RESULTS: Sensitivity and specificity for grading significant stenoses > or = 50% and occlusions (in parenthesis) were in the pelvic arteries 94.7%, 96.8%, (100%, 100%), in the arteries of the upper leg 92.3%, 93.3% (87.5%, 100%) and in the arteries of the lower leg 96.5%, 95.8%, (95.2%, 96.8%), respectively. Depiction of the runoff vessels of the lower leg was excellent in ceMRA. CeMRA was of diagnostic quality in all the patients. CONCLUSION: Contrast-enhanced MRA using a dedicated peripheral vascular coil system increases the diagnostic quality of the lower leg. The runoff vessels can be evaluated. Thus, ceMRA in the presented technique is a diagnostic alternative to arterial angiography. PMID- 11199444 TI - [Diagnostic radiological guidelines in the area of the head and neck]. PMID- 11199445 TI - [The Diagnosis Related Groups for Germany: "Clinician, take the lead!"]. PMID- 11199446 TI - [Australian Refined Diagnosis Related Groups. Formal and inherent problems of grouping with the example of stroke care]. AB - BACKGROUND AND OBJECTIVES: With the Health Reform 2000, the Australian Refined Diagnosis Related Groups (AR-DRG), Version 4.1 have been chosen as the basis for the future German costing system for hospitals. With regard to Stroke Severity (Barthel Index [BI]) we investigated to what extent the grouping according to AR DRGs can reproduce healthcare expenditures for such patients. Options to adapt and optimize the system are discussed. PATIENTS AND METHODS: 632 patients who had suffered a cerebrovascular accident and were discharged from conservative acute care in 1999, were classified according to the AR-DRGs. For the grouping we alternatively used data from the current hospital information system and a stroke database for quality assurance. The results were also compared with the clinical profiles for the public hospital sector of the corresponding DRGs in Australia (1997-98). RESULTS: On average 0.99 additional diagnoses per case were documented in the hospital information system, compared to 3.65 in the stroke database. In the stroke database 177 cases (36.8%) were assigned to the DRG with the highest cost weight. 53.7% of these patients suffered a serious stroke (BI < 30). Grouping on the basis of hospital information system data led only to 14 cases (2.8%) assigned to the DRG with the highest cost weight. CONCLUSIONS: Type and extent of additional diagnoses are crucial for the grouping process. From a clinical and economic point of view, measures of disability and impairment should be assigned to the grouping process to improve homogeneity under both aspects. Scores can also serve for determining reliable outcome parameters. For the development of an outcome related reimbursement system, procedures must be included in the definition of medical DRGs. In future, DRGs, which cover overlapping healthcare sectors, should be developed for patients with poststroke rehabilitation. PMID- 11199447 TI - [Assessment of teaching at the faculties of medicine in Germany]. AB - BACKGROUND AND OBJECTIVES: The aim of this study was to gather, against the background of a long-discussed deficit in academic teaching, data on the current activities of medical faculties with regard to teaching, and to analyse these findings. Another aim was to obtain suggestions for establishing a consensus on indicators that could be used to assess the quality of teaching. MATERIAL AND METHODS: In March 2000, a written inquiry was addressed to the deans of all 37 medical faculties in Germany. The questionnaire, arranged so that responses could be entered into a data-base, consisted of ten items in three parts. Part 1 concerned the evaluation of teaching, parts 2 and 3 dealt with the place of specific assessment of teaching in the process of choosing lecturers ("habilitation") and appointing senior professors. In addition to providing alternative answers (in some instances, allowing a choice of several alternatives) there was also space for written comments. The answers were analysed by descriptive statistics. RESULTS: All questionnaires were returned in a usable form (response rate 100%). 36 faculties had, at the time of receiving the questionnaire, already instituted teaching assessments, of clinical teaching sessions more often than preclinical ones (97% vs 89%). The most widespread method of assessment consisted of obtaining students' opinion and of using the centralized written examinations of the institute for Medical and Pharmaceutical Examination Questions. In more than half of the faculties (57%) an above-average teaching performance by teachers was acknowledged in special ways (honours/prizes). In 31 faculties (84%) teaching experience counted as an absolute prerequisite for obtaining a lectureship, but as a rule without employing any defined standards. With regard to the selection of senior professors, 27 faculties (73%) explicitly took teaching competence into account. Defined criteria for assessing teaching ability were largely absent. CONCLUSIONS: The assessment of teaching quality can be considered as well established at medical faculties in Germany. However, the methods and models used are highly heterogeneous. Furthermore, numerous activities exist in the various faculties to increase the importance attached to academic teaching. However, despite using diverse indicators of quality, the central problems for assessing teaching ability remain unsolved. PMID- 11199448 TI - [Food-dependent Cushing syndrome of long standing with mild clinical features]. AB - HISTORY AND CLINICAL FINDINGS: A 40-year-old woman complained of weight gain for 10 years. Because of this, she yearly went on a excessive weight reduction diet with weight loss of up to 12 kg. Nevertheless, a total weight gain of 15 kg as well as changing degrees of hypertension, muscular weakness and severe depression were registered during this long period. For 5 years ecchymosis and for 2 years oligomenorrhoea as well as oedema had become evident. Recently large macronodular adrenal glands were found on routine abdominal ultrasound. At the time of clinical investigation early this year she presented with relatively mild Cushing features, such as moon face, central obesity, hirsutism, ecchymosis and hypertension. INVESTIGATIONS: Endocrine testing demonstrated suppressed plasma ACTH, low to normal plasma cortisol after overnight fasting and an inverse diurnal rhythm. During 24 hours of fasting plasma cortisol levels and free urinary cortisol excretion were within normal range, but highly elevated under normal food intake. Plasma cortisol levels increased dramatically in response to a lipid-rich meal (5.6-fold), to a protein-rich meal (6.6-fold) and to oral glucose (3.7-fold). Increases in plasma cortisol were closely correlated to increases of gastric inhibitory polypeptide (GIP) concentrations. Subcutaneous injection of octreotide completely inhibited the plasma cortisol and GIP response to oral glucose. Plasma ACTH and cortisol levels did not increase after CRH administration, but fasting plasma cortisol promptly increased after ACTH stimulation. Non-fasting plasma cortisol levels and free urinary cortisol excretion were not suppressed by high doses of dexamethasone. Abdominal computed tomography showed macronodular enlargement of both adrenal glands. TREATMENT AND COURSE: The patient underwent bilateral adrenalectomy. Postoperatively, she was treated with replacement doses of hydrocortisone and fludrocortisone. All Cushing features have regressed, a normal menstrual cycle and normal plasma ACTH concentrations have become evident. CONCLUSION: This case report not only presents a very rare cause of Cushing's syndrome--food-dependent or gastric inhibitory peptide (GIP)-dependent hypercortisolism--but it also demonstrates a special course of this disease of relatively long duration. Severe adrenal hyperplasia contrasted with mild clinical symptoms obviously caused by frequent periods of weight reduction diet. Considering this moderate clinical course it might well be that food-dependent hypercortisolism is more frequent than supposed, but not diagnosed owing to relatively mild clinical symptoms. PMID- 11199449 TI - [Proton pump inhibitors in acute ulcer bleeding--what is evident?]. PMID- 11199450 TI - [Alternatives to standard therapy for bronchial asthma]. PMID- 11199451 TI - [Quo vadis, medicina?]. PMID- 11199453 TI - [Multiple primary carcinomas in patients with head and neck malignancies]. AB - BACKGROUND: Multiple primary tumors can lead to diagnostic and therapeutical problems. In this study we surveyed frequency, localisation, diagnostic, chronologic and therapeutic aspects of multiple primary carcinomas in patients with head and neck tumors. PATIENTS AND METHODS: The data of 843 patients from the tumor registry of the ENT-clinic Aachen were retrospectively studied. RESULTS: Larynx (41.87%) and oropharynx (12.57%) were the main localisation of the first primary neoplasma. In 65 patients (7.71%) multiple primary tumors were observed. 24.6% of these tumors occurred synchronously. Preferential localisation of a second tumor were lung (20%), oral cavity (15.3%) and larynx (13.8%). 28.57% of the metachronous tumors were observed after more than five years. In 46.15% clinical complaints led to the suspicion of a second tumor. Panendoscopy was the most reliable diagnostic procedure. The survival rate and time was significantly reduced in patients with synchronous tumors. 3-year survival rate was 15% compared to 81% in patients with metachronous tumor appearance (p < 0.0001). CONCLUSION: Patients with head and neck tumors have a high incidence of multiple primary malignomas varying from the region of the first presentation of a malignant tumor. Concepts comprising surgery provide the highest survival rates. Because of the high incidence of metachronous carcinomas after five years found in this study, the authors regard a prolonged follow-up period as necessary. PMID- 11199452 TI - [Prophylaxis of infection in neutropenic patients. Guidelines of the Working Party on Infections in Hematology and Oncology]. PMID- 11199454 TI - [Molecular biology and immunohistochemical prognostic markers in head and neck squamous epithelial carcinomas]. AB - BACKGROUND: Scientific research work of the last decade has been performed in order to investigate biological parameters of prognostic significance for head and neck squamous cell carcinoma. In contrast to other cancer types, like colon carcinoma, where tumour progression is accompanied by an almost defined sequel of gene activations and inactivations, cells of squamous cell carcinoma behave more heterogenously. METHODS: Publications concerning the most important immunohistochemical, molecular biological and cytogenetic prognostic markers in head and neck cancer have been analyzed. RESULTS: The prognostic markers discussed in this publication have been classified into the following areas: Apoptosis, cell cycle regulation, viral infections, cytokines and growth factors/growth factor receptors, angiogenesis and hypoxia, proteinases, cell-cell contacts and cell-matrix contacts, cytokeratin fragments, chromosomal rearrangements and genetically inherited susceptibility to toxic reagents. CONCLUSIONS: Significant prognostic markers are important for the clinical follow up of patients and the choice of therapeutical approach. However, none of the factors analyzed can be used as an individual and universal prognostic marker at present. PMID- 11199455 TI - [Coexpression of VEGF and bFGF is associated with increased vascular density in head and neck carcinomas]. AB - BACKGROUND: Angiogenesis is crucial for tumor growth and metastasis. In several tumors, microvascular density has been shown to correlate with metastasis and aggressiveness. Vascular endothelial growth factor (VEGF) and basic Fibroblast Growth Factor (bFGF) are known to have potent angiogenic activity. Their expression has been identified in a wide variety of malignancies including head and neck squamous cell carcinoma (HNSCC). Aim of our study was to investigate the role of co-expression of VEGF and bFGF for angiogenesis in HNSCC. MATERIAL AND METHODS: Cryostat sections of 51 primary HNSCC were immunostained for VEGF and bFGF using a standard streptavidin-biotin complex procedure. To evaluate angiogenesis, endothelial cells were stained immunohistochemically using anti-vWF polyclonal antibody. Microvessels were quantified by counting vessels in a x200 field in the most vascular area of the tumor. RESULTS: 25/51 (49%) of the investigated carcinomas showed co-expression of both factors (VEGF+/bFGF+), while 6/51 (11.7%) carcinomas only expressed VEGF and 13/51 (25.5%) carcinomas expressed bFGF. 7/51 (13.7%) tumors showed no expression of these factors (VEGF /bFGF-). Carcinomas with a co-expression of VEGF and bFGF showed a significantly increased mean microvessel density (88.3 +/- 24.4) compared to tumors expressing only VEGF (77 +/- 16.8) or bFGF (71.1 +/- 15.8) (p = 0.022) or tumors with no expression of both factors (51.1 +/- 13.4) (p < 0.001). The association of VEGF and bFGF expression level was not significant (p = 0.178). CONCLUSIONS: The positive correlation of the co-expression of angiogenic VEGF and bFGF with increased microvessel density underlines the importance of both factors for tumor angiogenesis in HNSCC. VEGF and bFGF might act cooperatively in the process of neovascularization in human head and neck cancer. PMID- 11199456 TI - [Classification and prognosis of esthesioneuroblastoma based on 7 treated cases]. AB - BACKGROUND: The esthesioneuroblastoma is a rare tumour of neuroectodermal origin, which arises usually in the area of the olfactory epithelium and invades the paranasal sinuses, the orbit and the brain. The low incidence of this disease makes a development of standardised clinical and histological classification difficult. Up to now this tumour is considered to be slow progressive but strained by a high rate of local recurrences. Metastasis are usually seen late at an advanced stage. PATIENTS: In the last 18 years 7 patients with an esthesioneuroblastoma were treated in our department. This relatively large number of patients allows a retrospective evaluation of the different already existing classifications concerning treatment and prognosis. RESULTS AND CONCLUSIONS: In all cases of a disease limited on the paranasal sinuses the patients were successfully treated either by a combination of resection and radiation (4 cases) or resection alone (1 case). No patient underwent a chemotherapy. Two cases with lethal outcome showed an extremely aggressive tumour progression. In such cases of extensive disease an additional chemotherapy has always to be taken into account. Our experiences and the analysis of the literature gives some indications that middle-aged patients have a worse prognosis than young or old patients. PMID- 11199458 TI - [Temperature and humidity profile of the paranasal sinuses before and after mucosal decongestion by xylometazolin]. AB - BACKGROUND: One of the most important functions of the nose is to warm and to humidify air before it reaches the lower respiratory tract. Nasal decongestants as one of the most common drugs used in otorhinolaryngology are often associated with the feeling of a "dry nose". The purpose of this study was to determine the short-term influence of xylometazoline on temperature and humidity in the nasal airways. METHODS: 15 healthy volunteers were enclosed into the study. A miniaturised humidity sensor and thermocouple was used for detection of humidity and airway temperature in the nasal vestibule, at the nasal valve area and in the nasopharynx at the end of inspiration. Measurements were done before and after topical application of xylometazoline. RESULTS: Temperature and relative humidity increase from the anterior parts of the nose to the nasopharynx at the end of inspiration. The temperature and humidity values after nasal decongestion are not significantly different from the values before application of xylometazoline. As a tendency temperature and humidity values after nasal decongestion are even somewhat higher at the nasal valve area compared to the values before application of xylometazoline. CONCLUSIONS: Widening of the nasal airways by mucosal decongestion did not lead to a significant change of the nasal temperature and humidity profile 20-30 min after application of xylometazoline. The use of xylometazoline seems not to influence humidifying and heating of inspired air within a short period after onset of the maximal decongestive effect of xylometazoline. PMID- 11199457 TI - [A new therapy concept in esthesioneuroblastoma]. AB - BACKGROUND: We introduce a new concept in treatment of esthesioneuroblastomas, developed in the University Medical School of Graz, Austria. PATIENTS AND METHODS: Six patients suffering from esthesioneuroblastoma have been treated in the years 1993-1999; five of them with a curative aspect, one with a palliative one. Three tumours were classified according to Kadish as stage B, three as stage C. The selection criteria included tumours without deep infiltration into the orbit nor into the pterygopalatine fossa and without any involvement of the posterior wall of the frontal sinus. The treatment consists of endoscopic nasal and paranasal sinus surgery and consecutive stereotactic radiosurgery by means of the Gamma-Knife unit. RESULTS: Over an average follow-up period of 38 months all patients remained free of disease. Because of the minimally invasive character of our concept the complications and side effects are minimised and the patients are less traumatised in comparison to conventional treatment such as craniofacial resection or irradiation. CONCLUSION: Due to the excellent outcome of our six patients we recommend this new treatment concept, in selected cases, as an alternative to the usual therapeutic modalities for esthesioneuroblastoma. PMID- 11199460 TI - [Local antibiotic administration decreases risk of inner ear damage in effodation]. AB - BACKGROUND: Mobilising the stapes via the removal of the tympanosclerotic plaques from the oval window niche (effodation) and stapedectomy or malleovestibulopexy are the different procedures generally available for the surgical therapy of stapes fixation due to tympanosclerosis. These techniques bear a significant risk of sensory hearing loss. Here we analyse our results using the mobilisation technique together with locally applied antibiotics. PATIENTS: Nineteen ears in seventeen patients with tympanosclerosis involving the stapes and its footplate which underwent stapes mobilisation between 1991 and 1999 have been investigated retrospectively. According to the literature this operation has a high risk of cochlear hearing loss. To reduce this risk, azlocillin was instilled locally during removal of tympanosclerotic plaques. RESULTS: Different operation techniques have been used: classic type III with placement of a cartilage disc on the head of the stapes (4), interposition of the incus (3), interposition of the head of malleus (1), interposition of a ceramic-PORP (6) and cartilage columella in cases of significant stapes footplate erosion (3). In two operations the chain was intact and no reconstruction was necessary. Pure-tone-audiometry showed no significant decrease of bone-conduction thresholds. Preoperatively 4 (21.1%) ears had an average air-bone-gap < or = 30 dB, while postoperatively 15 (78.9%) ears had this level of hearing. CONCLUSIONS: Until the exact causes of the loss of hearing after mobilisation or stapedectomy in cases of tympanosclerosis are known, the local administration of antibiotics is certainly recommended, bearing in mind the initial hypothesis that infection may be jointly responsible for cochlear hearing loss on mobilisation or stapedectomy in cases of tympanosclerosis. PMID- 11199459 TI - [Detection of central auditory compensation in unilateral deafness with functional magnetic resonance tomography]. AB - BACKGROUND: Functional magnetic resonance imaging (fMRI) is a noninvasive method to detect focal brain activity at high spatial resolution. Acoustic stimulation induces an increase of regional cerebral blood flow in the primary auditory cortex. This entails an increased concentration of diamagnetic oxyhemoglobin in the capillaries and the venous system. The resulting decrease of the local magnetic susceptibility was detected as a signal increase in T2*-weighted images. The central auditory pathways predominantly cross to the contralateral hemisphere in normally hearing subjects. The aim of the present study was to investigate the primary auditory cortex after acoustic stimulation in unilateral deaf patients using fMRI. METHODS: Magnetic resonance images were acquired on a 1.5 T Siemens Vision scanner. For fMRI, a single shot gradient recalled, echo planar imaging (EPI) sequence with decreasing excitation order was used, allowing the aquisition of 9 slices within 1.8 s. The 9 slices covered a slab of 3.6 cm in cranio-caudal extension in the region of the temporal lobes. For statistical processing of the raw image data the SPM96 software package was used. A p-value of p < 0.01 was applied to differentiate between activated and non-activated. The resulting functional activation maps were superimposed onto the EPI scan. The number of activated pixels was used to quantitate the cortical response upon acoustic stimulation. Stimulation consisted of a 1000-Hz sine tone (100 dB SPL at the distal end of the head phone, pulsed at 6 Hz) to which the patients were asked to listen passively. A piezoelectric loudspeaker was mounted on the subject table and connected to a plastic tube system leading to a combination of bilateral ear- and headphones. Auditory paradigms require disentangling experimental excitation from the scanner noise that approximates 90 dB. Headphones suppress noise by approximately 30 dB. To decrease the acoustic background-to-stimulation ratio and to keep background noise constant during stimulation and resting, we employed short scanning (1.8 s) and long resting periods (10.2 s; TR = 12 s). This acquisition mode allows sufficient recovery during off-periods and sufficient excitation during on-periods. 14 unilateral deaf patients were examined. The mean duration of deafness was 22.5 years. RESULTS: Acoustic stimulation of the deaf ear revealed only weak cortical activation which could be explained by sound transmission via bone conduction to the other ear. A significant increase of BOLD (blood oxygen level dependent)-activation in the primary auditory cortex could be demonstrated in all patients after stimulation of the hearing ear. However, remarkable individual differences were noticed concerning the absolute number of activated pixels. The lateralization ratio was calculated by the number of activated pixels on the hearing side divided by the number of activated pixels on the deaf side. A mean lateralization ratio of 0.9 (Stdv +/- 0.6) was found. The mean lateralization ratio for patients with a right deaf ear (n = 8) and those with a left deaf ear (n = 5) was 1.1 (Stdv +/- 0.7) and 0.6 (Stdv +/- 0.3) respectively. However, the difference was not significant (Wilcoxon test: p = 0.08). CONCLUSIONS: Central-auditory compensation by bilateral cortical activation was demonstrated in unilateral deaf patients. Moreover, a tendency towards a dominance of the left primary auditory cortex was found, although the difference between both hemispheres was not significant. The lateralization ratio in unilateral deaf patients is similar to findings after binaural stimulation in normally hearing subjects. PMID- 11199461 TI - [Scanning electron microscopy findings in titanium middle ear prostheses]. AB - BACKGROUND: Titanium as a biomaterial in ossicular replacement has widely spread within the last couple of years. METHODS: 23 prostheses (12 PORPs, partial ossicular replacement prostheses and 11 TORPs total ossicular replacement prostheses) removed during revision surgery were studied using scanning electron microscopy. The average implantation time was 8 (range 3-15) months. The specimens were investigated regarding tissue growth, epithelialization, inflammation and cellular signs of rejection. RESULTS: Only few prostheses were totally covered by connective tissue or epithelium due to technical problems in removing the implant and the covering tissue as one specimen. But this offered the possibility to study the interface at the edges where the tissue was torn off. The connective tissue looked unremarkable. Polygonal squamous epithelium was detected on several implants. Respiratory epithelium with ciliated cells and mucus producing goblet cells was seen in two specimens. In cases of cholesteatoma or protrusion the explanted prostheses showed typical rosette-like formation of hornifying squamous epithelium. According to underlying disease a lymphocytic infiltration could be seen. There were no cellular signs of incompatibility noticed neither macrophages nor foreign body giant cells. CONCLUSIONS: From these investigations titanium seems to be a favorable biomaterial for ossicular replacement with good acceptance also in an implantation site showing chronic inflammation. PMID- 11199462 TI - [Abducens paralysis from the viewpoint of the ENT physician and skull base surgeon]. AB - BACKGROUND: Among the nerves supplying the extraocular muscles, abducent nerve paralysis is the most common one resulting in double vision. Surveys confirm that the palsy is most often benign and transient. In most cases Ophthalmologist, Neurologist, Pediatrician and Physician are involved in diagnosis and treatment of this symptom. The Otorhinolaryngologist is needed in the least common cases of abducent nerve palsy due to intra- or extracranial diseases, for example trauma, inflammatory complications or tumors of the skull base. PATIENTS AND RESULTS: 12 patients (6 male, 6 female) with abducent nerve paralysis were seen and treated in the Department of Ear-Nose- and Throat Diseases, Head, Neck and Facial Plastic Surgery, Klinikum Fulda between 1984 and October 1999 and included in our series. Their records were evaluated and the main aetiology listed, was checked. An inflammatory process was the most common cause in 6 patients, one of them presented with otogenic meningitis and bilateral abducent nerve paralysis. In 4 patients neoplasm was the underlying pathology, in 1 patient head injury associated with temporal bone fracture and in 1 patient an orbital pseudotumor. Complete recovery of abducent nerve was achieved in 7 patients (58%). CONCLUSION: Using modern imaging techniques enables us to diagnose the aetiopathology of abducent nerve paralysis. Using modern imaging techniques, planning of therapeutic strategy and clarifying the prognosis of this symptom has improved considerably. PMID- 11199463 TI - [Diagnosis and treatment of necrotizing fasciitis of the head and neck region]. AB - BACKGROUND: Necrotizing fasciitis of the head and neck is a rare occurrence. It spreads rapidly along fascial planes causing extensive necrosis; it often results in gangrene of the overlying skin. Mostly involved are immunodeficient patients with banal infections of the upper aerodigestive tract, small traumas, but also after surgical procedures. The "Federal Health Agency" of the Federal Republic of Germany estimates a number of 40 cases a year in Germany for all regions of the body. The mortality is about 20%-50% dependent on the localisation of this soft tissue infection. PATIENTS: Four cases of necrotizing fasciitis of the head and neck region, which were treated at the ENT-Department of the Martin Luther University Halle-Wittenberg since 1995, were described. RESULTS: Despite aggressive surgical debridement and intensive care medicine two patients died because of streptococcus-associated-toxic-shock-syndrome. In all patients we found a diabetes mellitus as a known risk factor for this necrotizing soft tissue disease. In two of four patients with cervical involvement mediastinitis was diagnosed as a complication. The CT-scan showed this mediastinal spread only in one case. CONCLUSIONS: Only rapid diagnosis and surgical treatment with radical debridement can influence the disease positively. Thoracal CT-scan is necessary in all cases of cervical necrotizing fasciitis because of the high risk of mediastinal involvement. A strong complication is a streptococcus-associated toxic-shock-syndrome, which should be prevented because it is often associated with a lethal outcome. Penicillin G and clindamycin are advocated for antibiotic treatment. PMID- 11199464 TI - [Water-jet dissection in parotid surgery--initial clinical results]. AB - INTRODUCTION: The most frequent complication following parotidectomies is postoperative facial nerve dysfunction. In animal experiment we successfully studied the technique of water-jet-dissection for safe and functional preservation in facial nerve dissection in parotid gland surgery. The aim of the present study was to evaluate our animal experiments clinically. METHODS: Until November '99 ten patients with benign parotid gland tumors (4 female, 6 male, age 32-77 years) underwent lateral or latero-segmental parotidectomies using water jet-dissection ("Hydro-Jet", Andreas Pein Medizintechnik GmbH, Schwerin, Germany). All operations were performed under permanent intraoperative facial nerve monitoring ("Neurosign 100", Fa. Inomed, Tenningen, Germany). The postoperative facial nerve function was measured daily by the House-Brackmann and Stennert-Paresis-Index for at least one week. RESULTS: A quick parotid gland and safe facial nerve dissection could be performed in all operations using the 120 microns-nozzle with effective working pressures from 30-50 bar. In addition strong connective tissue fibers were transected with scissors. Intraoperative facial nerve lesions did not occur and cardiopulmonary complications due to eventual cutting-fluid-resorption were not seen. After surgery all patients had a normal facial nerve function. DISCUSSION: The results of our studies showed that the technique of water-jet-dissection provides safe facial nerve dissection and preservation during parotid gland surgery. CONCLUSIONS: The tissue selective cutting qualities of the new surgical method are an excellent alternative compared to standard dissection methods in parotid surgery. PMID- 11199465 TI - [Medical aspects of diving in otorhinolaryngology. I. Barotrauma and decompression sickness]. AB - Recreational scuba diving has become immensely popular in recent years and is no longer restricted to individualists or adventurers. During a dive, the human body with its gas-filled cavities is exposed to an increased ambient pressure. In the present review article, aspects of diving and hyperbaric medicine related to the otolaryngology field are presented. The basics of physics, physiology and pathophysiology that are essential to understand the effects of an increased and varying ambient pressure are reviewed. Barotrauma of the outer, middle and inner ear, the paranasal sinuses, face, teeth and larynx are explained and classified in those during the compression and decompression phase. This is followed by a discussion of inner ear decompression sickness. The present article will provide a background and foundation for both, an adequate treatment of these diseases and a critical and responsible health education of the diver. PMID- 11199466 TI - [Electrophysiological diagnosis of the caudal cranial nerves]. AB - The lower cranial nerves (CN. IX-XII) are responsible for the nerve supply of the pharyngolaryngeal region. Loss of innervation is manifested by dysphagia, aspiration, altered speech production, dyspnea and/or stridor, and visible loss of movement. In general electrophysiological testing should be applied in every kind of paresis. Beside standard equipment for electromyography limited special equipment is necessary. Examination under local anaesthesia is possible and can serve as a basis for therapeutic consequences. In this article general aspects as seen from an oto-rhino-laryngological standpoint are presented. PMID- 11199467 TI - [Interesting case no. 40. Complete esophageal stent obstruction by dental prosthesis impression material]. PMID- 11199468 TI - [Functional impairment of outer hair cells by noise and assessment by measuring distortion product emissions (DPOAE)]. PMID- 11199469 TI - Does [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]- dichloroplatinum(II) act on the hormone-sensitive, murine breast cancer as a biological response modifier? Part II. Studies on the influence of [meso-1,2 bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine] dichloroplatinum(II) on the specific immune defense in MXT-M-3,2 breast cancer bearing mice. AB - The anti-tumor activity of [meso-1,2-bis(2,6-dichloro-4- hydroxyphenyl)ethylenediamine]dichloroplatinum(II) on the MXT-M-3,2 breast cancer implanted into B6D2F1 mice was not significantly reduced by splenectomy or co administration of cyclosporine A. Neither did the use of T-lymphocyte-deficient NMRI (nu/nu) mice as hosts substantially influence its anti-tumor effect. Obviously, [meso-1,2-bis(2,6-dichloro-4- hydroxyphenyl)ethylenediamine]dichloroplatinum(II) does not act by an enhancement of the specific immune defense. PMID- 11199470 TI - Does [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]- dichloro platinum(II) act as an immune response modifier? Part III: Progressively growing MXT-M-3,2 breast cancer stimulates the proliferation of phagocytes in B6D2F1 mice. AB - MXT-M-3,2 breast cancer implanted into female B6D2F1 mice accelerates the growth of an identical second tumor. This process is accompanied by a significant increase of the granulocyte and monocyte numbers in the blood and of the granulocyte and macrophage numbers in the spleen. A significant positive correlation of strong intensity was found between the tumor weight on the one hand and the number of the granulocytes and macrophages on the other hand. The tumor-dependent promotion of the myelopoiesis is explained with a secretion of hematopoietic growth factors, e.g. of the granulocyte-macrophage-stimulating growth factor (GM-CSF), by the breast cancer cells. PMID- 11199471 TI - Studies on synthesis, chromatographic resolution, and antiinflammatory activities of some 2-thioxo-1,2,3,4-tetrahydropyrimidines and their condensed derivatives. AB - In this study, the synthesis of some new 2-thioxo-1,2,3,4-tetrahydropyrimidines and their condensed derivatives, thiazolo[3,2-a]pyrimidines, are described. The structures of the compounds were confirmed by 1R, 1H-NMR, 13C-NMR, and mass spectroscopy. The direct high-performance liquid chromatographic separation of the compounds on derivatized cellulose chiral stationary phases such as cellulose tris(3,5-dimethylphenylcarbamate) (OD), cellulose tris(4-methylphenylcarbamate) (OG), and cellulose tris(4-methylbenzoate) (OJ) was studied. All of the compounds were screened for their antiinflammatory activity and also investigated histopathologically. Compounds 3 and 1a were found to be the most promising antiinflammatory agents in this group. PMID- 11199472 TI - Crosslinked polyvinylalcohol hydrogels as vehicles for hydrophilic drugs. AB - Polyvinylalcohol crosslinked with succinyl, adipoyl, or sebacoyl chloride at two different degrees of crosslinking was prepared and employed as a supporting material for aqueous topical gels containing propranolol hydrochloride, which was chosen as a hydrophilic model drug suitable for transdermal delivery. We analysed the effect of the nature of the crosslinker and the degree of crosslinking on drug permeation through porcine skin by means of the permeation parameters obtained from the gels and the corresponding aqueous solution. The gels showed greater drug permeation than the liquid solution due to an increase in drug solubility in the skin. Increasing degree of crosslinking and decreasing crosslinker acyl chain length in the gel enhance the drug permeability through the skin. PMID- 11199473 TI - Synthesis, structure, and binding of some 2-imidazolines to rat brain alfa-1 and alfa-2-adrenergic receptors. AB - A series of novel 2-[(2-aminophenyl)imino]imidazolinium salts 3a-d and N-benzyl-N (4,5-dihydro-imidazol-2-yl)-O-methylhydroxylamine hydrochloride 7a-c were prepared and their structure was determined by IR and NMR spectroscopic data as well as X-ray analysis of the imidazolinium azide salt 3e. Binding evaluation for both alpha 1- and alpha 2-adrenergic receptors in rat brain preparations of these compounds and the previously described alpha-hydroxy-2-aryliminoimidazolines 11a d, N-(4,5-dihydroimidazol-2-yl)-1,3-2-oxodihydrobenzimidazoles 12a-b, 2-amino-N (4,5-dihydroimidazol-2-yl)-benzimidazoles 13a-b, and N-(4,5-dihydroimidazol-2-yl) indoles 14a-b was performed. Among the compounds tested, 2-[(2-amino-4,5 dichlorophenyl)imino]imidazolinium chloride 3c showed highest binding affinity to alpha 2-adrenoreceptors (Ki = 30 nM). PMID- 11199474 TI - Novel piperidinedione analogs as inhibitors of breast cancer cell growth. AB - We previously reported the utility of antineoplaston-A10 (3-phenylacetylamino-2,6 piperidinedione) as an endogenous cancer protector and immune modulator in breast cancer patients (Cancer Lett., 2000, 157, 57). In this study, four new piperidinedione A10 analogs were synthesized and tested for their antimitotic activity on a human breast cancer cell line against the prototype A10 and the antibreast cancer drug tamoxifen. Moreover, the DNA binding capacity of such compounds was evaluated against A10, (E)-3-(4-Nitrocinnamoylamino)-2,6 piperidinedione "3B" and (E)-3-(4-hydroxycinnamoylamino)-2,6-piperidinedione "3D" were several-fold more potent antiproliferative agents than A10 and tamoxifen. They also had significantly higher capacity to bind DNA than A10. Conversely, (E) 3-(cinnamoylamino)-2,6-piperidinedione "3A" and (E)-3-(4-methoxycinnamoylamino) 2,6-piperidinedione) "3C" had weaker biological profiles than the lead compound A10. Detailed synthetic, spectroscopic, and biological data are reported. PMID- 11199475 TI - Mini review of canine stifle joint anatomy. AB - The stifle is a complex, condylar, synovial joint that allows motion in three planes. The complexity of the normal motion is directly related to the structure and functions of the anatomical components that form the joint. Alteration in any one of these components often leads to dysfunction as well as an increased risk of damage to other structures in the joint. Thus understanding of the normal anatomy and function of each stifle joint component is essential for proper diagnosis and treatment of any stifle joint injury. This review highlights the basic anatomy and function of the stifle joint components. PMID- 11199476 TI - Light and electron microscopic study of the thyroid gland of the camel (Camelus dromedarius). AB - The thyroid gland of sexually immature dromedary camels was studied using both light and electron microscopy. The thyroid gland contained follicles of different sizes in both summer and winter. However, most of the follicles were large in summer and small in winter. The large follicles were lined by very low cuboidal or semi-squamous follicular cells whereas the small ones were lined by high cuboidal or low columnar follicular cells. Electron microscopy showed that the very low cuboidal follicular cells were poor in organelles and were considered hypoactive. High cuboidal follicular cells on the other hand, were rich in organelles that included mitochondria, cisternae of rough endoplasmic reticulum, secretory vesicles, colloid droplets, heterosomes and autophagic vacuoles; they were considered to be very active. The possible role played by these organelles is synthesis of thyroglobulin and liberation of tri- and tetraiodothyronine is discussed. A few degenerate follicular cells were infrequently encountered in the camel thyroid. Parafollicular (C) cells were not seen in this study either with light or electron microscopy. PMID- 11199477 TI - Anatomical and descriptive study of the radial extensor muscle (M. extensor carpi radialis). AB - The M. extensores carpi radiales have been studied in detail in humans. The aim of this study was to carry out a comparative anatomical study of these muscles using four species--rabbit, cat, dog and sheep--and to propose a 'systematization' in a few standard models according to the morphological variations seen. In these species, there is marked morphological evolution, with two muscles in humans, one in sheep and a more or less distinct division of the muscle in the rabbit, cat and dog. Examination of the vascularization and nerve supply enables us to determine degrees of division in species with similar muscle morphology. Thus we were able to distinguish three morphological types which allow us to infer the morphological evolution of the M. extensores carpi radiales and to estimate the point at which one muscle became two. However, there is a strong chance that some process of convergence may have occurred, and in pentadactyl species many elements represent the plesiomorphis and are therefore of little use in constructing a classification on the basis of evolution. PMID- 11199478 TI - Immunohistochemical demonstration of cytochrome oxidase in different parts of the central nervous system: a comparative experimental study. AB - Cytochrome oxidase, the terminal enzyme of the electron transport chain, is a marker of the functional activity of the cell. In this study; localization of cytochrome oxidase in cerebrum, cerebellum, hippocampus, substantia nigra and choroid plexus of adult rats was investigated using immunohistochemical methods. Neural bodies were immunoreactive while neuroglial cells and axonal areas did not show significant immunostaining. The cerebral cortical substantia grisea region was stained almost homogeneously with cytochrome oxidase. In the cerebellar cortex, immunolabelling was more intense in the granular layer than the molecular layer. There was significant immunostaining in Purkinje cells. White matter, both in cerebrum and cerebellum, did not show immunoreactivity for cytochrome oxidase. Neurones in the hippocampus showed variable immunostaining; some of them were negative while others revealed high immunoreactivity. The neurones in substantia nigra were heavily labelled. Immunostaining for cytochrome oxidase in plexus choroideus epithelial cells was also remarkable. The morphological findings demonstrate the regions which most require and produce energy and reflect the differences in cellular activity in these parts of the central nervous system. PMID- 11199479 TI - The effects of two different decalcification procedures on size and structure of embryonic epithelial tissue in objects prepared for light microscopy. AB - Electrolytic decalcification is a very fast and effective method for removing calcium compounds from bones with minimum damage to tissues. Changes of dimension of tissues in histological sections prepared from specimens decalcified by immersion in a formic acid solution and sections prepared from specimens treated in an electrolytic decalcifier were studied. Heads of mouse foetuses were cut in half, decalcified by one of the above-mentioned methods and embedded in histowax. Dimensional changes of skin, tongue and nasal epithelia in histological sections were evaluated by t-test. Significant shrinking and other unwanted effects of decalcification, such as acidophilia of nuclei, were found in objects decalcified by both methods. No significant differences in the effects of the two methods on tissue dimensions were demonstrated. It is concluded that both decalcification methods are equivalent from the qualitative point of view. PMID- 11199480 TI - Cell-specific localization of the cholecystokininA receptor in the porcine pancreas. AB - Cholecystokinin (CCK) produced in the mucosa of the upper small intestine exerts several biological functions. Its secretion in physiological amounts is modulated by the interaction of extracellular regulators and by binding to intracellular receptors of the target cells. The relative affinity of CCK to its receptor has been characterized in various biological and pharmacological studies and it is now well established that CCK has a higher affinity to the CCKA than to the CCKB receptor. Furthermore CCK influences the secretion of pancreatic enzymes in several species but very little is known about the relationship between CCK and the islet hormone-producing cells in the pig pancreas. The localization of this receptor at the cellular level showed conflicting results in animal studies and has not been described in pigs. The aim of the present study was to characterize the precise cellular location of the CCKA receptor in the porcine pancreas. Polyclonal antiserum was raised against the N-terminal epitope of the CCKA receptor molecule and used for localization studies. Using immunohistochemistry on methanol/acetic acid-fixed, paraffin-embedded pancreas, the CCKA receptor could successfully be localized in islet cells. Parallel staining of serial sections with antibodies directed against insulin and glucagon revealed colocalization with glucagon in alpha cells. No immunoreaction was found in the exocrine pancreas. Our results support the concept that in the porcine species the stimulation of the exocrine pancreas is mediated by the CCKB rather than the CCKA receptor, as it is known for the rat species. PMID- 11199481 TI - Teratogenicity of edoferon kappa A, a molecule derived from salicylate, in cultured rat embryos: differences from salicylate and interaction with free oxygen radical scavenging enzymes. AB - The effect of edoferon kappa A (E-KA), a non-specific immunomodulatory and anti neoplastic chemical substance derived from the methyl form of salicylate (acetyl salicylic acid; ASA), on mammalian embryos was studied and compared to the effects of ASA. Rat embryos were cultured in vitro from 9.5 days of gestation for 48 h. E-KA (0.1-12.8 mg/ml) and ASA (0.1-0.6 mg/ml) were added to the whole rat serum. To investigate the interaction of these molecules with antioxidant agents, the lowest effective concentrations of E-KA (0.6 mg/ml) and ASA (0.3 mg/ml) for all parameters were added to the culture media in the presence of superoxide dismutase (SOD) (30 U/ml) or glutathione (0.5 mumol/ml). The growth and development of embryos was compared and each embryo was evaluated for the presence of any malformations. E-KA and ASA decreased growth and development in a concentration-responsive manner. There was also a concentration-related increase in overall dysmorphology (haematoma in the yolk sac and neural system, open neural tube, abnormal tail torsion and the absence of fore limb bud). There were no statistically significant differences between the control and embryos grown in the presence of 0.1-0.4 mg/ml E-KA, although the effects of ASA started at a concentration of 0.2 mg/ml. Embryos showed significant growth retardation in all scoring criteria and severe malformations when 0.5-3.2 mg/ml E-KA and 0.3-0.6 mg/ml ASA were added. When SOD was added, there was a significant decrease in the incidence of malformations and growth and developmental parameters were increased but this decrease never reached the control level. We concluded that E-KA has direct toxic effects on the developing embryo but at much higher concentrations than ASA, and the teratogenic effects of these molecules might be related to free oxygen radicals. PMID- 11199482 TI - Morphology of the dorsal lingual papillae in the black rhinoceros (Diceros bicornis). AB - The dorsal lingual surface of a black rhinoceros (Diceros bicornis) was examined by scanning electron microscopy. The tongue was about 30 cm in length. There were about 60 vallate papillae on both sides. Filiform, fungiform and vallate papillae were found. The filiform papillae were distributed over the entire dorsal surface of the tongue. The papillae had a hair-like shape. The fungiform papillae were round in shape, and more densely distributed on the lingual apex. No foliate papillae were seen on the dorsal surface. The vallate papillae were located on both sides of the posterior end of the lingual body. Each papilla was surrounded by a groove. PMID- 11199483 TI - Distribution of tyrosine hydroxylase-immunoreactive neurones in the diencephalon and mesencephalon of the coypu (Myocastor coypus). AB - The aim of the present study was to examine the catecholaminergic neurones located within the midbrain of the coypu, a South American hystricomorph rodent. The neuronal distribution of the catecholaminergic systems and morphological parameters of the immunostained cell bodies and fibres were investigated, using an immunohistochemical method. The brains of five coypu were fixed, immersed in gelatine-glycerol and cut in 40-micron slices using a freezing microtome. Samples were processed with ultrasound-based antigen retrieval and stained with labelled antityrosine hydroxylase monoclonal antibody. An image analyser was used to measure the neuronal bodies. The catecholaminergic neurones of the tuberoinfundibular system were mainly observed in the arcuate and periventricular nuclei with their axons projecting towards to the median eminence; they represented 28% of the global population of tyrosine hydroxylase-immunoreactive cells observed. Significant morphological differences were observed in comparison with the other two studied systems. Fifty per cent of total catecholaminergic neurones were detected in the nigrostriatal system distributed in the reticular and compact substance nigra. Most neuronal bodies had a fusiform aspect. The immunoreactive neurones of the mesolimbic system represented 22% of the total population. They were distributed around the interpeduncular nucleus. Two types of morphologically different catecholaminergic systems of the brain were established: hypothalamic neurones located in the periventricular and arcuate nuclei and mesencephalic neurones located in the substance nigra and interpeduncular nuclei. These systems showed morphological and probably physiological-pharmacological differences. PMID- 11199484 TI - Comparative studies on the distribution of glutamate transporters in the retinae of the Mongolian gerbil and the rat. AB - Glutamate is the major excitatory amino acid transmitter in vertebrate retinae. Glutamate transporters therefore play an important role in the precise control of glutamate concentration in the synaptic cleft by regulating extracellular glutamate concentration. In the present study, we performed an analysis of the expressions of three glutamate transporters in gerbil retina using immunohistochemistry. In the gerbil retina, excitatory amino acid carrier 1 and glutamate transporter 1 immunoreactivity was predominant in the ganglion cells but not amacrine or bipolar cells. Glutamate/aspartate transporter (GLAST) immunoreactivity was observed in the radial gliocytes of which the dense network of fine processes was localized in the inner and outer plexiform layers. GLAST immunoreactivity was also detected in astrocytes in the nerve fibre layer. These results demonstrate that three glutamate transporters show specific distributions in the gerbil retina and suggest that the glutamate re-uptake system in the gerbil retina may be different from that of the rat. PMID- 11199485 TI - [Weismann's potentially immortal single cells are mortally self-cloning cells]. AB - The theory of Weismann (A. F. L. Weismann, 1834-1914) is reviewed in the light of recent genetic experiments and considerations. PMID- 11199486 TI - Distribution of peptidergic nerve fibres in the guinea pig trabecular meshwork. AB - A quantitative analysis of peptidergic nerve fibres located in the trabecular meshwork of the guinea pig has been performed. Our results confirm that this structure contains VIP-, NPY- and substance P-like immunoreactivity as major neurotransmitters. These findings were obtained using immunohistochemical techniques. For this purpose serial sections of the eye were stained by immunohistochemistry for each of three neurotransmitters and stained sections were analysed by quantitative image analysis. Our findings demonstrate that SP positive, NPY-positive and VIP-positive nerve fibres occupy 11.2, 4.9 and 2.4%, respectively, of the observed area (expressed as conventional units, C.U.) in the trabecular meshwork of the guinea pig eye. It is relevant to emphasize that the area containing these three types of peptidergic nerve fibres appears to be large (18.5 +/- 6.6 C.U.) in proportion to the total observed area. The innervation of the drainage angle of the guinea pig eye has been well described by many authors. This is the first study to report quantitative measurements of three types of peptidergic nerve fibres identified and measured in this area. The presence of these three neurotransmitters in the trabecular meshwork of guinea pig eye suggests their possible participation in aqueous humor regulation. PMID- 11199487 TI - Ultrastructural features of myenteric ganglia of adult Wistar rats (Rattus norvegicus). AB - The ultrastructural features of the ganglia of the myenteric plexus exhibit changes according to the animal species. These myenteric ganglia in the duodenum of adult rats of the Wistar strain were characterized ultrastructurally in this work. Those ganglia were depicted as compact structures, composed of neurones and glial cells, forming a dense neuropil surrounded by a continuous basal lamina and collagen fibrils. Glial cell bodies were smaller and apparently more frequent than neuronal cell bodies, being morphologically distinguished by nuclear features. In the neuronal extensions granular and agranular synaptic vesicles of different sizes predominate, in addition to mitochondria and myelinized profiles. Gliofilaments were not observed on the glial extensions of the rats. PMID- 11199488 TI - Evidence for high affinity nickel transporter genes in heavy metal resistant Streptomyces spec. AB - We have isolated 25 new strains of streptomycetes from soil samples of a polluted site at the former uranium mine, Wismut, in eastern Thuringia, Germany. The strains grew on medium containing 1 mM NiCl2 and thus were resistant to the heavy metal ion. Seven of the strains were further characterized. All of these strains were resistant to heavy metals in various degrees with up to 10 mM resistance against NiCl2 supplied with the liquid minimal growth medium. The high level of resistance prompted us to look for high affinity nickel transporter genes thought to provide a means to eliminate the excess nickel ions form the cells. Degenerate oligonucleotide primers derived from sequences of P-type ATPase transporter genes of Gram negative bacteria identified a fragment which shows deduced amino acid sequence similarities to known high affinity nickel transporters. Investigation of two genes obtained from the isolates Streptomyces spec. E8 and F4 showed high sequence divergence. This was unexpected since a transmissible plasmid had been thought to convey heavy metal resistance. PMID- 11199489 TI - Isolation of an 1,3-1,4-beta-glucan degrading Enterococcus faecium strain from the intestinal tract of chicken and partial characterization of its novel 1,3-1,4 beta-glucanase. AB - An Enterococcus faecium strain with a novel endo 1,3-1,4-endo-beta-glucanase (lichenase, E.C. 3.2.1.73) was isolated from the intestinal tract of broiler chicken. The enzyme was secreted into the culture medium and acted exclusively on mixed linked 1,3-1,4-beta-glucans as determined with a reducing sugar assay. The purified enzyme has its isoelectric point at pI 4.8, maximum activity was determined at pH 6.5 and 40 degrees C. Thermal stability of the enzyme was low, but high pH stability and high residual activity was observed after incubation in digesta samples from the chicken intestine. Multiple lichenase activities were obtained from culture supernatants on SDS/PAGE and native zymograms, but it is concluded that the lichenase consists of one active protein at 30.5 kD and additional polypeptides of unknown function. PMID- 11199490 TI - Bacterial amylolytic activity enhances beta-glucuronidase expression of amylase negative Escherichia coli strain in starch-medium. AB - The possibility of associating starch degradation with bacterial beta glucuronidase expression was examined. We proved that starving, in starch medium, amylase-negative Escherichia coli (M94) which has constitutive beta-glucuronidase greatly reduces (p < 0.01) its background activity, but the addition of both cell free supernatants or cells of Bacillus subtilis (B10) producing amylase greatly increases (p < 0.01) the E. coli beta-glucuronidase activity. Increases in activity were maximal when amylase in the medium ranged from 0.3 to 0.8 U ml-1 and pH from 6.8 to 6.3, whereas higher amylase activity interacted with E. coli viability and the effect on beta-glucuronidase was less evident. The impact of B. subtilis amylase on E. coli beta-glucuronidase induction, observed when the organisms were co-cultured, indirectly supports the hypothesis that amylolytic activity of hindgut bacteria may be effective on beta-glucuronidase induction of the climax microflora. This last finding is important in the health field, considering the implication between the deconjugating role of this enzyme and consequent activation of toxic and carcinogenic compounds. PMID- 11199491 TI - Sequential synthesis and secretion of pectinases by Penicillium frequentans. AB - Penicillium frequentans synthesized eleven polygalacturonases and three pectinesterases when grown in the presence of pectin, sodium polypectate or monogalacturonic acid. When glucose was the sole carbohydrate source in the medium two of these polygalacturonases and one pectinesterase were produced. The enzymes produced under any of these conditions degraded pectic substrates to monogalacturonic acid, suggesting that this monosaccharide or its metabolites should induce the pectinolytic complex. All pectinesterases and most of the extracellular polygalacturonases were synthesized after the 2nd hour of incubation. The pectinases produced by Penicillium frequentans were not secreted at the same time but after 5 hours of incubation all of them could be detected outside the cell those detected only inside the cell were probably membrane associated or unglycosylated forms of the extracellular pectinases. PMID- 11199492 TI - Rosaria succina spec. nov.--a fossil cyanobacterium from tertiary amber. AB - A fossil cyanobacterium found in a piece of Tertiary amber is assigned to the recent genus Rosaria N. Carter (Stigonemataceae) and described as R. succina. The fossil allows a new systematic evaluation of the genus Rosaria. PMID- 11199493 TI - Influence of inoculum type and cultivation conditions on natamycin production by Streptomyces natalensis. AB - This study demonstrates the effect of cultivation conditions on the production of natamycin. Of these conditions, the effect of oxygen limitation and type of inoculum were extensively investigated. Increasing the shaking speed and decreasing the medium volume improved both the volumetric and specific natamycin production. Also, decreasing the dissolved oxygen level in the cultivation medium through the addition of soluble biopolymer (alginate) resulted in a significant decrease in the natamycin yield without effect on the cell growth. On the other hand, spore inoculum yielded higher concentration of natamycin compared to the vegetative cells by about 40%. The maximal cell productivity based on biomass [Yp/x] of about 0.4 [g/g] was obtained by using shake flask of 50 ml working volume agitated at 200 rpm and the inoculum was in the form of spore 2 x 10(8) spores/ml. These results showed that the production process of natamycin is highly dependent on oxygen level in the cultivation medium and type of inoculum as well. PMID- 11199494 TI - Bacterial counts associated with poultry processing at different sampling times. AB - Aerobic plate counts, Enterobacteriaceae counts and Pseudomonas counts were performed on neck skin samples from six processing steps in a poultry abattoir at three different sampling times. Sampling time 1 was shortly after start-up of processing operations, time 2 after a tea break which was preceded by a cold water rinse-down of equipment surfaces, and time 3 before shut-down. No significant differences (P > 0.05) in microbial numbers of neck skin samples were observed between the three sampling times at the six sampling sites. At this particular processing plant, therefore, sampling at any time of the processing shift would thus not lead to significantly different bacterial counts of neck skins. The lowest aerobic plate counts, over all three sampling times, were obtained for neck skins sampled after spray washing, and the highest for neck skins sampled after packaging. This indicated the efficacy of the washing step in reducing microbial contamination but subsequent re-contamination of carcasses. Despite the Pseudomonas counts of neck skins being lower than the Enterobacteriaceae counts at the beginning of processing, packaging of carcasses resulted in Pseudomonas counts that were higher than the Enterobacteriaceae counts. PMID- 11199495 TI - Biological and molecular characterization of cellular differentiation in Tetrahymena vorax: a potential biocontrol protozoan. AB - Tetrahymena vorax (T. vorax) is an indigenous fresh water protozoan with the natural biological potential to maintain a specific aquatic microbial flora by ingesting and eliminating specific microorganism. To investigate the molecular mechanisms controlling Tetrahymena vorax (T. vorax) cellular differentiation from a small-mouth vegetative cell to a voracious large-mouth carnivore capable of ingesting prey ciliates and bacteria from aquatic environments, we use DNA subtraction and gene discovery techniques to identify and isolate T. vorax differentiation-specific genes. The physiological necessity for one newly discovered gene, SUBII-TG, was determined in vivo using an antisense oligonucleotide directed against the 5' SUBII-TG DNA sequence. The barriers to delivering antisense oligonucleotides to the cytoplasm of T. vorax were circumvented by employing a new but simple procedure of processing the oligonucleotide with the differentiation stimulus, stomatin. In these studies, the antisense oligonucleotide down-regulated SUBII-TG mRNA expression, and blocked differentiation and ingestion of prey ciliates. The ability to down regulate SUBII-TG expression with the antisense oligonucleotide suggests that the molecular mechanisms controlling the natural biological activities of T. vorax can be manipulated to further study its cellular differentiation and potential as a biocontrol microorganism. PMID- 11199496 TI - New enzymatic method for determining D-arabinitol in serum. AB - A new reagent has been developed to determine D-arabinitol. This utilizes D arabinitol 2-oxidoreductase derived from Bacillus sp. with high stability, and water-soluble tetrazolium salt, that can detect NADH with high sensitivity. Since this enzyme does not react to D-mannitol, elimination of D-mannitol is unnecessary. Thus, this is a much simpler process than currently available with commercial kits use D-arabinitol 4-oxidoreductase. The within-run and between-run precisions (CV) were 2.4-6.9% and 3.1-8.7%, respectively, whilst the correlation (r) between the results obtained with our proposed method (y) and those obtained with the commercial "Arabinitec-auto" kit (x) was 0.964 (y = 1.02x + 0.933 mumol/l; n = 69). However, some samples deviated remarkably from correlation in both methods. Our analyzing accuracy is satisfactory in clinical application, as it does not miss positive sample over cut-off value. We are refining this method by investigating why some specimens are apart from correlation significantly. PMID- 11199497 TI - Factors affecting the production of (-)-mitorubrinic acid by Penicillium funiculosum. AB - The optimum conditions for the production of (-)-mitorubrinic acid by mutant strain of Penicillium funiculosum CCM F-8080 were examined in shaken flask cultures. The highest production of this metabolite was achieved in a medium with glucose as the sole carbon source and (NH4)2HPO4 as the nitrogen source. The most suitable concentrations of the given sources for production of (-)-mitorubrinic acid are 80 g/l glucose and 2 g/l (NH4)2HPO4 (maximal production, 814.9 mg/l). We also observed the influence of concentration of L-phenylalanine and inorganic phosphate in culture medium on the production of (-)-mitorubrinic acid. The biological activity of mitorubrinic acid as trypsin inhibitor was determined (IC50 41.05 mumol/l). PMID- 11199498 TI - A highly homologous 68 kbp plasmid found in Vibrio vulnificus strains virulent for eels. AB - Vibrio vulnificus serovar E (biotype 2) strains are virulent for eels and have also been reported to cause illness in humans. Studies on the plasmid content of serovar E strains revealed the existence of a plasmid of approximately 70 kbp present in most of these strains. In this study we characterized the 70 kbp plasmids of seven biotype 2 strains isolated from seawater, diseased eels and wound infections in humans. We determined the exact size of the high molecular weight plasmids to be 68 kbp. A comparison of the plasmids of the seven strains by restriction length polymorphism and hybridization analysis showed them to be almost identical. PMID- 11199499 TI - Diversity of Bacillus thuringiensis in different habitats of northern Jordan. AB - A survey of Bacillus thuringiensis was conducted for 17 locations in Northern Jordan representing 12 different habitats. Eighty isolates were identified as B. thuringiensis in the majority of the tested samples. Results showed that soils contaminated with the slaughterhouses waste materials had the highest content of spore-forming bacteria [(4.05-2.2) 10(7) CFU/g)] and B. thuringiensis [(4.05-7.9) 10(7) CFU/g)] with a (5.5%-14.9%) and (5.2%-7.7%) of the total viable bacterial count, respectively. These bacteria were more abundant in soils contaminated with such animal by-products. PMID- 11199500 TI - Metabolism of benzonitrile by Cryptococcus sp. UFMG-Y28. AB - The yeast Cryptococcus sp. UFMG-Y28 can utilize benzonitrile as a nitrogen and possible additional carbon source. The kinetics of growth on Yeast Carbon Base (YCB) added of benzonitrile as sole nitrogen source showed that benzonitrile was metabolized to benzoic acid and ammonia. Liquid chromatography analysis indicated that Cryptococcus sp. UFMG-Y28 metabolized 12 mM benzonitrile to 10 mM benzoic acid. Resting cells cultivated on YCB-propionitrile medium showed nitrilase activity against benzonitrile. This strain appears to be promising for bioconversion of nitriles to high value acids and for bioremediation of sites contaminated with aliphatic and aromatic nitriles. PMID- 11199501 TI - Comparative growth of ectomycorrhizal basidiomycetes (Hebeloma spp.) on organic and inorganic nitrogen. AB - In the largely organic soils in which ectomycorrhizas are commonly found, a preference for absorbing organic nitrogen over mineral forms is likely to be an advantage, especially where mineralisation rates are low. To determine rates of both independent and preferential growth of ectomycorrhizal basidiomycetes on organic and inorganic nitrogen, strains of Hebeloma were grown on nutrient agar media containing either NH4+ or glutamic acid as the sole source of nitrogen, on both single medium and split plate Petri dishes. Growth rates on the split plate Petri dishes, where the fungi had access to both nitrogen sources, were generally greater than on the single medium dishes. Growth on glutamic acid was at least equal to, and usually greater than, that on NH4+. In some cases growth on NH4+ alone appeared severely inhibited, a condition that was partially alleviated by access to glutamic acid on the split plates Petri dishes. This highlights a potential pitfall of single nitrogen source growth studies. The greater growth of most strains on glutamic acid suggests an adaptation to organic nitrogen utilisation in these strains. If this is so in soils with low mineralisation rates, direct uptake of amino acids by ectomycorrhizal plants could by-pass the bottle neck that requires mineral nitrogen to be made available for plant uptake. PMID- 11199502 TI - Exopolysaccharide production by entrapped cells of the fungus Aureobasidium pullulans ATCC 201253. AB - The production of the exopolysaccharide pullulan using entrapped cells of the fungus Aureobasidium pullulans ATCC 201253 was investigated. Fungal cells entrapped in agarose or carrageenan were capable of elaborating pullulan for 2 production cycles. Those fungal cells entrapped in carrangeenan were more productive than the agarose-immobilized cells during the initial cycle while the reverse was true during the second production cycle. The agarose-entrapped cells synthesized polysaccharide with a higher pullulan content than did the carrageenan-immobilized cells. Fungal cells entrapped in carrageenan demonstrated a lower degree of leakage than did those entrapped in agarose. PMID- 11199503 TI - Primary leiomyosarcoma of the heart subsequent to double carcinomas of the thyroid and lung. AB - A 63-year-old woman underwent surgical operations for left lower lung cancer and for thyroid cancer. Nine months later, a third cancer developed in her heart and this tumor was removed by open heart surgery. A pathologic study revealed that the tumor was primary leiomyosarcoma of the heart and thus independent from the previous lung and thyroid carcinomas. This case was regarded as a triple carcinoma including a primary leiomyosarcoma arising from the left atrium. Reports in the literature on primary malignant tumors of the heart are reviewed briefly. PMID- 11199504 TI - Prognostic value of Doppler transmittal flow patterns and cardiac natriuretic peptides in patients with chronic congestive heart failure admitted for episodes of acute decompensation. AB - This study was designed to determine whether the restrictive filling transmitral flow velocity pattern is associated with increased plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). It was also designed to evaluate the prognostic value of these parameters from patients with chronic congestive heart failure (CHF) admitted for episodes of acute decompensation. We performed Doppler echocardiography, measured plasma levels of ANP and BNP in 33 patients at the time of admission, and assessed the subsequent cardiac mortality for 3 months. Eleven patients (33%) had a restrictive filling pattern of deceleration time (DcT) < 120ms. Plasma ANP and BNP levels were markedly increased in all patients to 189 +/- 145 pg/ml and 865 +/- 559 pg/ml, respectively. Seventeen patients (52%) showed more than 700 pg/ml of plasma levels of BNP. There was a significant correlation of DcT with the plasma ANP level (r = -0.41, P = 0.017), and a better correlation of DcT with the plasma BNP level (r =-0.50, P = 0.003). The combined index of both shorter DcT (< 120 ms) and higher plasma BNP levels (>700 pg/ml) was the best predictor of cardiac mortality by Cox univariate analysis (chi2 = 5.87, P = 0.015). Furthermore, the sensitivity and specificity of this index for the detection of cardiac mortality were 80% and 86%, respectively. In conclusion, the combined analysis of the Doppler transmitral flow velocity pattern and measurement of the plasma BNP level is noteworthy since it is noninvasive and convenient. Moreover, it is extremely useful in predicting the prognosis for patients with chronic CHF admitted for episodes of acute decompensation. PMID- 11199505 TI - Pulmonary arterial compliance in children with atrial and ventricular septal defect. AB - Previous studies have documented the normal values of pulmonary arterial compliance (Cp) in animals and adult humans. In the past, variations in Cp and its measurement in children with septal defects has been unknown. In the present study, we found the Windkessel model, which uses compliance and resistance as parameters, to be a useful tool in understanding Cp in pediatric patients. Calculations of Cp were based on the pulmonary arterial diastolic pressure waveform as an exponential function of time. First, Cp was estimated by studying pressure tracings of the main pulmonary artery (MPA) obtained from both routine cardiac catheterization and pressure measured by a catheter-tip manometer, which was performed during a catheterization study of seven children with various congenital heart diseases. Second, 124 children with atrial and ventricular septal defects aged between 45 days and 12 years were studied using the data obtained from routine catheterization. Hemodynamic data were used to calculate pulmonary vascular resistance (Rp), pulmonary arterial time constant (Tp) and Cp. A strong correlation (r = 0.954) was found in the Cp value estimated by data obtained from routine catheterization and from the catheter-tip manometer study. The present study shows an estimated mean (SEM) Cp in normal children of 1.53 (0.17) ml/mmHg per m2. The estimated mean (SEM) Cp was 1.91 (0.10) and 1.70 (0.11) ml/mmHg per m2 in children with atrial septal defect (ASD) and ventricular septal defect (VSD), respectively. It was found that Cp was significantly (P = 0.04) higher in female patients with a VSD. Also, a significantly low Cp (0.95 +/ 0.06 ml/mmHg per m2) was observed in patients with a VSD and pulmonary hypertension (VSDPH). In conclusion, Cp was calculated by the exponential decay portion of the MPA diastolic pressure waveform. A normal Cp value was observed in ASD and VSD patients and a significantly low Cp was observed in children with a VSDPH. Cp was higher in female VSD patients than in male VSD patients. PMID- 11199506 TI - Effects of a phosphodiesterase III inhibitor on circulating blood volume after cardiopulmonary bypass. AB - Using a new method based on pulse dye densitometry, circulating blood volume (BV) was measured without direct sampling in patients undergoing open-heart surgery, and the effects of phosphodiesterase (PDE) III inhibitor administration during cardiopulmonary bypass (CPB) were evaluated. Sixteen patients scheduled for elective coronary artery bypass grafting were randomly assigned to the PDE III inhibitor group or control group. BV was determined before CPB, and immediately, and 4 and 12h after operation. After declamping of the aorta, the PDE III inhibitor amrinone (1 mg/kg) was infused as a single bolus into the venous reservoir in the PDE III inhibitor group. BV decreased significantly soon after the operation in the control group. It did not decrease in the PDE III inhibitor group (48.6 +/- 44 and 60.6 +/- 8.0 ml/kg for the control and PDE III inhibitor groups. respectively). Four hours after surgery and beyond no significant changes in BV were observed in either group. The body fluid balance was negative in both groups. In conclusion, a single administration of PDE III inhibitor during CPB was found to sustain BV soon after operation and, therefore, is useful for postoperative management of open-heart surgery. PMID- 11199507 TI - Effect of overexpression of very low density lipoprotein receptor on cell growth. AB - The very low density lipoprotein (VLDL) receptor is a member of the LDL receptor gene family and binds only apoE-containing lipoproteins. Although the VLDL receptor has been shown to play an important role in the proliferation of vascular smooth muscle cells and the formation of foam cells as primary responses of atherogenesis, its actual functions are still unclear. To understand the biological roles of the VLDL receptor in foam cell formation and cell growth, we tried to overexpress VLDL receptors in various cells. When COS-7 cells were transfected with an expression plasmid containing VLDL receptor cDNA, cell growth was inhibited by overexpression of the receptor and this growth inhibition was ligand-independent. The O-linked glycosylation region, but not the cytoplasmic domain, of the receptor appeared to be responsible for this growth inhibition. On the other hand, VLDL receptor expression induced enhanced incorporation of lipids and cytoplasmic enlargement. These changes were dependent on the exogenous ligand and the cytoplasmic domain of the receptor. These results suggest that the VLDL receptor functions as a regulator of cell growth and differentiation, which may be distinct from its lipid-incorporating function. PMID- 11199509 TI - Right heart bypass for left circumflex coronary artery bypass grafting. AB - Displacement of the heart to expose the left circumflex artery (LCX) causes hemodynamic disturbance during off-pump coronary artery bypass grafting (CABG). We applied right heart bypass (RHB) using a heparin-coated centrifugal pump without an oxygenator in an attempt to stabilize the hemodynamics. Five mongrel dogs (15.5-20 kg) were used. Hemodynamic parameters were continuously monitored at a fixed rate of 80 beats/min. The LCX was exposed with the use of an Octopus Tissue Stabilizer. After baseline data were obtained, each dog was placed in the Trendelenburg position. Finally, RHB was established with different pump flows. LCX exposure caused a significant decrease in aortic flow (to 33.1% +/- 13.1% of the baseline value) and arterial mean pressure (to 68.3% +/- 8.5%) (P < 0.001). Trendelenburg positioning caused these values to recover to 57.1% +/- 6.7% and 72.5% +/- 7.7%, respectively. RHB with 50% flow significantly improved the hemodynamic values, although 100% flow significantly increased LAP by 134.8% +/- 19.7% (P < 0.01). Tilting of the canine heart to expose the LCX caused significant deterioration of the hemodynamic values. Trendelenburg positioning was moderately effective, and RHB very effective, in improving the hemodynamics. In a limited number of cases, an appropriate flow of RHB may provide safe hemodynamic assistance during off-pump CABG of the LCX. PMID- 11199508 TI - Nicorandil increases adenosine 5'-monophosphate-primed interstitial adenosine via activation of ecto-5'-nucleotidase in rat hearts. AB - With the use of microdialysis techniques, we examined the effects of nicorandil, a hybrid of an ATP-sensitive K+ (K ATP) channel opener and a nitrate compound, on the production of interstitial adenosine in rat hearts in situ. The level of dialysate adenosine measured under a constant supply of adenosine 5' monophosphate (AMP) reflected the activity of endogenous ecto-5'-nucleotidase. Nicorandil (0.3-3mM) increased the level of AMP (100 microM)-primed dialysate adenosine in a concentration-dependent manner, and this effect was completely abolished by the guanylate cyclase inhibitor, methylene blue (100 microM), but not by the K ATP channel blocker, glibenclamide (10 microM). Another K ATP channel opener, cromakalim (0.1-1mM), did not increase the production of AMP primed dialysate adenosine. These results suggest that nicorandil increases the level of interstitial adenosine via cyclic guanosine monophosphate-mediated activation of ecto-5'-nucleotidase. PMID- 11199510 TI - Gallic acid induces vascular smooth muscle cell death via hydroxyl radical production. AB - In the present study, we investigated whether gallic acid (GA) can induce death in cultured vascular smooth muscle cells (VSMCs), and whether production of the hydroxyl radical (.OH) is involved in the process of GA action. GA killed cultured VSMCs from rat aorta, in a dosc- and time-dependent manner. Cytoplasmic shrinkage and nuclear condensation were observed light microscopically in GA treated VSMCs, which appeared apoptotic. However, the ultrastructure of the VSMC was not typical of apoptosis: nuclear condensation was not glossy, and the plasma membrane and subccellular organelles were disrupted. Although the VSMC were positive for in situ nick end-labeling (TUNEL). they did not show a DNA ladder pattern on gel electrophoresis and were negative for T aq polymerase-based in situ ligation, which is more specific for apoptosis than TUNEL. Moreover. GA induced cell death was not prevented by Boc-Asp-fmk (a pan-caspase inhibitor). Production of OH was detected in GA-treated VSMCs using high-performance liquid chromatography with salicylic acid as a trapping agent. Lipid peroxidation was also observed. The production of .OH was inhibited by catalase (CAT) and deferoxamine (DFX), and these treatments completely rescued VSMCs from cell death. In a cell-free system, GA produced .OH in the presence of Fe2+-EDTA, which was quenched by CAT and DFX, suggesting involvement of the Haber-Weiss reaction. Oxidative stress by reactive oxygen species, .OH in particular, is one of the mechanisms of GA-induced death of VSMCs, the mode of which was different from typical apoptosis. PMID- 11199511 TI - Scrub jays (Aphelocoma coerulescens) form integrated memories of the multiple features of caching episodes. AB - Four experiments examined whether food-storing scrub jays remember when and where they cached different foods. The scrub jays cached and recovered perishable and nonperishable foods in visuospatially distinct and trial-unique cache sites. They rapidly learned to avoid searching for foods that had perished by the time of recovery, while continuing to search for the same foods after shorter retention intervals when the foods were still fresh. The temporal control of searching at recovery was also observed when the familiarity of cache sites did not provide any information about the time of caching and when the same food was cached in distinct sites at different times. The authors argue that the jays formed an integrated memory for the location and time of caching of particular foods. PMID- 11199512 TI - Cognitive precedence for local information in hierarchical stimulus processing by pigeons. AB - Four experiments investigated the processing of hierarchical stimuli by pigeons. Using a 4 alternative divided-attention task, 4 pigeons were food-reinforced for accurately identifying letters arranged as either hierarchical global- or local relevant stimuli or as size-matched filled stimuli. Experiment 1 found that task acquisition was faster with local-relevant than global-relevant stimuli. This difference was not due to letter size. Experiment 2 demonstrated successful transfer to a novel irrelevant letter configuration. Experiments 3 and 4 tested pigeons' responses to conflict probe stimuli composed of equally discriminable relevant letters at each level. These tests revealed that all of the pigeons showed a cognitive precedence for local information early in processing, with the pigeons using different cues to initiate the processing of global information. This local advantage contrasts with previously reported results for humans and pigeons but is similar to that reported for nonhuman primates. Alternatives attempting to reconcile these contrasting comparative results are considered. PMID- 11199513 TI - Taste preconditioning augments odor-aversion learning. AB - On the basis of previous work that has shown a taste can potentiate odor-aversion conditioning in AX+ conditioning, 6 experiments used rats to examine the effects of pairing a preconditioned taste (A) with a novel odor cue (X) in an A+/AX+ aversion conditioning design. Experiments 1A and 1B demonstrated that a preconditioned taste produced a robust odor aversion that was significantly stronger than a potentiated odor aversion. The results of Experiment 2 showed that the robust odor aversion produced by A+/AX+ conditioning was not the result of the potentiated odor aversion summating with generalization from the taste aversion. The augmented odor aversion was produced only when the taste and odor stimuli were presented simultaneously (Experiment 3) and the preconditioned taste aversion was intact at compound conditioning (Experiment 4). Pairing a novel odor with a preconditioned taste was not sufficient to condition an aversion to odor (Experiment 5), although other results implicated a role for an association between odor and taste in the odor augmentation effect (Experiment 6). The present results have implications for current models of taste + odor interactions in flavor-aversion conditioning. PMID- 11199514 TI - Conditioned inhibition produced by extinction-mediated recovery from the relative stimulus validity effect: a test of acquisition and performance models of empirical retrospective revaluation. AB - Empirical retrospective revaluation is a phenomenon of Pavlovian conditioning and human causal judgment in which posttraining changes in the conditioned response (Pavlovian task) or causal rating (causal judgment task) of a cue occurs in the absence of further training with that cue. Two experiments tested the contrasting predictions made by 2 families of models concerning retrospective revaluation effects. In a conditioned lick-suppression task, rats were given relative stimulus validity training, consisting of reinforcing a compound of conditioned stimuli (CSs) A and X and nonreinforcement of a compound of CSs B and X, which resulted in low conditioned responding to CS X. Massive posttraining extinction of CS A not only enhanced excitatory responding to CS X, but caused CS B to pass both summation (Experiment 1) and retardation (Experiment 2) tests for conditioned inhibition. The inhibitory status of CS B is predicted by the performance-focused extended comparator hypothesis (J. C. Denniston, H. I. Savastano, & R. R. Miller, 2001), but not by acquisition-focused models of empirical retrospective revaluation (e.g., A. Dickinson & J. Burke, 1996; L. J. Van Hamme & E. A. Wasserman, 1994). PMID- 11199515 TI - Relative validity effects with either one or two more valid cues in Pavlovian and instrumental conditioning. AB - Two experiments investigated the relative validity effect with either 1 or 2 continuously reinforced cues in Wistar rats using appetitive Pavlovian and instrumental preparations. Discrimination training involved 3 compound cues containing a common element (1AX: 1BX: 2CX). In the first true-discrimination group (TD-1), CX was followed by food, but AX and BX were not. In the second true discrimination group (TD-2), AX and BX but not CX were followed by food. In the third, pseudodiscrimination group (PD), food followed 50% of each compound. Compared with the PD group, there were lower levels of responding to X in Groups TD-1 and TD-2, which did not differ. That is, both TD treatments showed equivalent relative validity effects. There was evidence for a relative validity effect on the context. The Rescorla-Wagner model incorrectly predicts a smaller relative validity effect after the TD-2 than the TD-1 treatment. Comparator theory predicts these results. PMID- 11199516 TI - Circadian time perception. AB - The variability of anticipating a meal was investigated. Sprague-Dawley rats earned food by inspecting a food source during a 3-hr interval. Food was not available at other times. In Experiment 1, the meal started 3 or 7 hr after light offset in a 12-hr light-dark cycle. Experiment 2 was conducted in constant darkness with 14-, 22-, 22.5-, 24-, 25.5-, 26-, or 34-hr intermeal intervals. Inspections increased before the meal. Rats timed intervals in the circadian range (22-26 hr) with lower variability than that for intervals outside this range (3-14 and 34 hr). Higher precision in timing selected intervals violates the scalar property. Proximity to a circadian oscillator improves timing precision. Variability may be used to identify oscillators with noncircadian periods. PMID- 11199517 TI - Stability and variability in extinction. AB - Some studies have found that extinction leaves response structures unaltered; others have found that response variability is increased. Responding by Long Evans rats was extinguished after 3 schedules. In one, reinforcement depended on repetitions of a particular response sequence across 3 operanda. In another, sequences were reinforced only if they varied. In the third, reinforcement was yoked: not contingent upon repetitions or variations. In all cases, rare sequences increased during extinction--variability increased--but the ordering of sequence probabilities was generally unchanged, the most common sequences during reinforcement continuing to be most frequent in extinction. The rats' combination of generally doing what worked before but occasionally doing something very different may maximize the possibility of reinforcement from a previously bountiful source while providing necessary variations for new learning. PMID- 11199519 TI - On opening of the National Practitioner Data Bank. PMID- 11199518 TI - New York needs to take lead in ethics training. PMID- 11199520 TI - Palm trees. PMID- 11199521 TI - NYSDA Membership Survey. How the components stack up. AB - There are many similarities and differences between the demographic characteristics of dentists, their practice arrangements, business activities, income and other factors, which do not follow the purported "downstate-upstate" dichotomy. In each district society, most respondents are sole proprietors, and 26+ years is the most frequently reported period of time in practice. A great majority of dentists in most component societies work 32+ hours per week, and average 50 to 56 scheduled and six to nine emergency visits per week. $175,000+ was reported most frequently as the net income of dentists in eight component societies. A small percent of practitioners belong to IPAs and capitation plans. A small percent accepts Medicaid patients. A somewhat larger percent belongs to DR plans. A much greater percent belongs to PPO arrangements. Approximately 25% of respondents expect that their primary occupation will change in the next 10 years, with the vast majority anticipating no longer being in dental practice. PMID- 11199522 TI - The man-eaters with bad teeth. AB - Two cases of man-eating lions feeding on large numbers of humans (1898, 1991) are discussed. The forensic dental evidence from the lions' remains and eyewitness reports indicate all three lions had serious dental/oral pathology, which may have contributed to their selection of human food over more challenging natural animal prey. PMID- 11199523 TI - Macrognathia of renal osteodystrophy in a dialysis patient. Report of a case. AB - A case of macrognathia secondary to renal osteodystrophy in a dialysis patient is presented. The case reviewed demonstrates a variety of radiographic and histopathologic features, some of which resemble fibrous dysplasia and others suggestive of Paget's disease of bone. This article contains diagnostic criteria for differentiating renal osteodystrophy from similar fibro-osseous diseases. There is a discussion of the underlying cause and appropriate therapeutic interventions of renal osteodystrophy. PMID- 11199524 TI - Restoration of endodontically treated tooth containing wide or flared canal. AB - There has been much anecdotal information and misinformation disseminated regarding the restoration of endodontically treated teeth, which has comprised the foundation for our restorative protocol. In the past, it was considered appropriate to place a cast post and core in every pulpless tooth without regard to the amount of remaining supportive tooth structure present. Recent developments in available ceramics, greater cosmetic demands by patients, and the advent of adhesive bonding techniques have caused clinicians to reevaluate their restorative protocol. This article reviews the current literature with regard to restoration of the endodontically treated tooth and presents a method for restoration and reinforcement using a combination of polyethylene ribbon and a prefabricated fiber post to create a post and core that is retentive, supportive, cosmetic and able to impart reinforcement to a structurally compromised root. PMID- 11199525 TI - Is there a doctor on the plane? PMID- 11199526 TI - If you've got it, advertise it. PMID- 11199527 TI - Irukandji and Chironex fleckeri jellyfish envenomation in tropical Australia. AB - OBJECTIVE: To compare the temporal distribution of Irukandji and Chironex fleckeri stings, the demographics of victims, the prevailing physical conditions at the time of a sting, and the prevalence of unsuitable first aid strategies. METHODS: Retrospective assessment of 478 Chironex and 544 Irukandji stings in Queensland and the Northern Territory of Australia. RESULTS: Adolescent and young adult males were the most common victims of Irukandji (median age 21 years) and Chironex stings (median age 16 years). Most Chironex stings occurred on the legs, while Irukandji stings were more common on the arms. Vinegar was correctly used to remove tentacles in 90.5% of Chironex stings, whereas inappropriate treatments were used in the remaining cases. Chironex stings were reported in every month in the Northern Territory, and in all months but June and July in Queensland. The peak prevalence for Chironex stings occurred in January in both areas, while the number of Irukandji stings peaked in December in Queensland and in May in the Northern Territory. Chironex stings were more common on still, cloudy days, whereas Irukandji stings were more common on still, clear days. Irukandji stings were more frequent than Chironex stings on rough days (P = .0005). Chironex and Irukandji stings were similar with respect to tides, moon phases, and rainfall. CONCLUSIONS: This study failed to predict exact weather patterns or other contributing factors to reduce the risk of stings to an acceptable level, but did identify several factors that increase the incidence of stings. The "stinger free" season reported on Chironex warning signs is inaccurate and should be changed to warn bathers that Chironex may be present year round, particularly in the Northern Territory. PMID- 11199528 TI - Optimization and preliminary characterization of venom isolated from 3 medically important jellyfish: the box (Chironex fleckeri), Irukandji (Carukia barnesi), and blubber (Catostylus mosaicus) jellyfish. AB - OBJECTIVE: To optimize venom extraction and to undertake preliminary biochemical studies of venom from the box jellyfish (Chironex fleckeri), the Irukandji jellyfish (Carukia barnesi), and the blubber jellyfish (Catostylus mosaicus). METHODS: Lyophilized crude venoms from box jellyfish tentacles and whole Irukandji jellyfish were prepared in water by homogenization, sonication, and rapid freeze thawing. A second technique, consisting of grinding samples with a glass mortar and pestle and using phosphate-buffered saline, was used to prepare crude venom from isolated nematocysts of the box jellyfish, the bells of Irukandji jellyfish, and the oral lobes of blubber jellyfish. Venoms were compared by use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS PAGE) and Western blot test. Toxicity of some venoms was determined by intravenous median lethal dose assay in mice. RESULTS: Different venom extraction techniques produced significantly different crude venoms for both box and Irukandji jellyfish. Irukandji and blubber venom SDS-PAGE protein profiles were established for the first time. Analysis of Western blot tests revealed that box jellyfish antivenin reacted specifically with the venom of each jellyfish. Toxicity was found in Irukandji jellyfish venom derived by use of the mortar-and pestle method, but not in the lyophilized venom. CONCLUSIONS: Glass mortar-and pestle grinding and use of an appropriate buffer was found to be a simple and suitable method for the preparation of venom from each jellyfish species studied. This study contributes to biochemical investigations of jellyfish venoms, particularly the venom of the Irukandji jellyfish, for which there are, to our knowledge, no published studies. It also highlights the importance of optimizing venom extraction as the first step toward understanding the complex biological effects of jellyfish venoms. PMID- 11199529 TI - Inhaled nitric oxide improves survival in the rat model of high-altitude pulmonary edema. AB - OBJECTIVES: High-altitude pulmonary edema (HAPE) afflicts certain individuals after a rapid gain in elevation. Those susceptible demonstrate an exaggerated hypoxic pulmonary vasoconstrictive response. This causes pulmonary hypertension, which may disrupt vascular integrity. This experiment was designed to test whether inhaled nitric oxide would affect development of HAPE in a rat model. METHODS: Subjects were exposed in a hypobaric chamber to a simulated altitude of 6200 m (barometric pressure = 380 mm Hg, fraction of inspired oxygen = 0.19) for 24 hours. Control animals (n = 48) spontaneously breathed a mixture of 90% room air and 10% nitrogen, whereas the nitric oxide group (n = 48) received a similar mixture containing 83 ppm nitric oxide. Postmortem examination of lungs was performed for light microscopy, total hemoglobin, and gravimetric estimates of water content. RESULTS: Mortality was 39.5% (n = 19) in control animals and 6.2% (n = 3) in the nitric oxide group (P < .001). Both groups significantly increased their lung weight-body weight ratio. Percentage of lung water was similar in both groups despite increases in lung weight, which is consistent with the protein rich edema characteristic of HAPE. Light microscopic examination of survivors' lungs in both groups revealed scattered alveolar hemorrhage. No significant cellular inflammatory response was present. CONCLUSIONS: We conclude that inhaled nitric oxide improves survival in the rat model of HAPE. PMID- 11199530 TI - Planning for an annual episodic mass gathering: emergency department and clinic utilization in Yellowstone. AB - OBJECTIVE: Planning and providing emergency and primary care for a large transient population of visitors and employees in a national park can be problematic. Furthermore, planning for emergency and primary health care needs of visitors and itinerant workers in a wilderness area national park has not been well documented. A study was performed to analyze emergency and primary health care utilization in a national park. METHODS: Data was gathered from all patients presenting to Lake Hospital Emergency Department in Yellowstone in 1995, and a retrospective chart review was performed. RESULTS: Two distinct populations with different health care needs were identified. CONCLUSION: Utilization analysis revealed differences between conventional mass gatherings and the mass gatherings in Yellowstone. Because of the unique conditions and populations found in a wilderness area, conventional mass gathering emergency medical service models may not be an appropriate model for planning health care in a national park. Analysis of utilization data can help plan resources for emergency and primary health care for a park population. PMID- 11199531 TI - Practical aspects in mountain medicine education. AB - Mountain medicine education is provided through many different courses. The newest developments include an international Union Internationale des Associations Alpinistes--Internationale Kommission fur Alpines Rettungswesen- International Society of Mountain Medicine (UIAA-IKAR-ISMM) label for mountain medicine courses that comply with certain minimal requirements in theoretical and practical educational aspects. Participants in the courses that fulfill these specific conditions are eligible to obtain the International Diploma of Mountain Medicine, which is recognized by the above-mentioned international bodies governing mountain sports and mountain medicine. The Swiss course cycle, and especially the structure and content of the Swiss summer course 1999, which was organized by the Swiss Alpine Club and the Swiss Society for Mountain Medicine, are described in this article and some annotations are given. Theoretical and practical requirements for obtaining the International Diploma of Mountain Medicine in Switzerland are also presented. PMID- 11199532 TI - Clinical images. Immersion injury. PMID- 11199533 TI - Joseph Lister, antiseptic surgery, and wilderness medicine--a commentary. PMID- 11199534 TI - Illustrations of the antiseptic system of treatment in surgery. 1867. PMID- 11199535 TI - Creative anatomy teaching. PMID- 11199536 TI - Brains and video games at high altitude. PMID- 11199537 TI - Acclimatization of genetically related adults and children. PMID- 11199538 TI - The millennium and beyond. PMID- 11199539 TI - The limitations of learning from a clinical diagnosis of "probable high-altitude pulmonary edema". PMID- 11199540 TI - Medical emergencies at high altitude. PMID- 11199541 TI - Death from high-altitude pulmonary edema preventable by appropriate treatment. PMID- 11199542 TI - Lifting spirits and restoring dignity. PMID- 11199543 TI - An unusual alteration in the shape of a tooth. AB - Dental anomalies are an important issue and dentists should be able to manage these conditions. Often, treatment is not necessary; however, some abnormalities may affect the esthetics or function of teeth and can lead to other problems. This case report presents an unusual case of alteration in shape affecting the left lower canine in a 34-year-old woman. PMID- 11199544 TI - Potassium nitrate. PMID- 11199545 TI - Gift ethics. PMID- 11199546 TI - AGD and the ADA. PMID- 11199547 TI - The new COX-2 inhibitors: rofecoxib (Vioxx) and celecoxib (Celebrex). PMID- 11199548 TI - Experimental therapy research in general dental practice. PMID- 11199549 TI - Evidence-based dentistry and esthetics. AB - Separating hype from the truth in dental marketing can be frustrating and it is difficult at best for the average dentist to evaluate the safety and efficacy of new products and techniques. Keynote clinicians are presenting information and influencing other dentists without the scientific evidence to support their claims. For the benefit of our patients, the system needs to change. It will not come soon, but until more evidence-based testing is commonplace and made readily available to the practicing dentist, most dentists will continue tradition-based practices. PMID- 11199550 TI - Anterior mandibular radiolucency. Glandular odontogenic cyst. PMID- 11199551 TI - Radiolucency of maxillary alveolus. Fibrous scar. PMID- 11199552 TI - Comprehensive treatment planning involving implant reconstruction. PMID- 11199553 TI - A comparison of all-ceramic restorative systems: Part 2. AB - Overall, any of these systems can provide well-fitting, natural looking restorations as long as care is taken during the preparation and fabrication procedures. A key to successful use of all-ceramic materials is proper selection based on the clinical conditions involved in specific restorative procedures (see table). All systems have limitations on their use and when we try to stretch those limits, success rates may fall drastically. High stress areas should shift selection to high strength, clinically documented materials. Low stress areas requiring high translucency may be restored successfully using the lower strength castable glasses. Intermediate areas may shift selection to higher strength yet still translucent materials such as In-Ceram Spinell or Empress 2. Posterior regions might best be addressed with the use of In-Ceram Alumina or Procera. The case of posterior bridges would lock the selection into In-Ceram Zirconia. Finally, it is important for each of us to continually educate ourselves and to examine the evidence in order to make an informed decision and maximize clinical success. PMID- 11199554 TI - Recognition of bulimia nervosa in dental patients: implications for dental care providers. AB - Patients with bulimia nervosa commonly exhibit distinctive oral characteristics. Dental health providers should be able to recognize these signs and identify patients with this condition. Members of the dental health team then must intervene and assist in facilitating treatment of the eating disorder. Current knowledge about bulimia nervosa and its oral signs and preventive, interventive, and restorative strategies for dental health practitioners are presented. PMID- 11199555 TI - Drug use for the pregnant or lactating patient. AB - The dental patient who is pregnant or lactating may require management involving the administration or prescription of drugs. The approach of completely avoiding all drugs may not permit appropriate treatment of the patient and most often is not warranted. This article reviews the current considerations in the use of drugs in the dental patient who is either pregnant or lactating. The safety of the local anesthetics, vasoconstrictors, analgesics, antimicrobials, and sedatives used in dentistry is discussed. PMID- 11199556 TI - Oral condyloma acuminatum. AB - Oral condyloma acuminatum is a papillomatous lesion that is transmitted sexually and associated with the human papilloma virus. Condyloma acuminatum generally appears one to three months after exposure to an infected partner and presents in multiple form in the oral cavity. PMID- 11199557 TI - Desensitization of exposed root surfaces using a semilunar coronally positioned flap. AB - A definitive treatment is described for cervical dentinal sensitivity, featuring a semilunar coronally positioned flap to cover the denuded root surface. Many patients who complain of having sensitive teeth from exposed dentin secondary to gingival recession can be easily and conservatively treated with a semilunar flap procedure. PMID- 11199558 TI - Incorporating Piaget's theories into behavior management techniques for the child dental patient. AB - This presentation reviews psychologist Jean Piaget's contributions to knowledge of cognitive development in children, relating it to behavior management techniques. Piaget theorized that children's knowledge about reality is realized by touching and observing; he termed this constructivism. He recognized that there are stages of development in knowledge acquisition. Practitioners should try to stimulate these needs to develop a positive dental experience. Another Piaget model is egocentrism, wherein a child views the world subjectively. The dentist should let the child patient know what's going on and have an active part in treatment. PMID- 11199560 TI - Patient satisfaction. PMID- 11199559 TI - Class V lesions restored with flowable composite and added surface sealing resin. AB - This in vitro study evaluates the marginal sealing ability of three different flowable composite systems at enamel and dentin margins, using sealants. Class V preparations were made on the facial surfaces in enamel and dentin/cement of 60 freshly extracted teeth, which were allotted randomly into six groups of ten. The control groups (I, II, and III) showed leakage in the majority of cases. However, Groups IV and V had very limited microleakage scores (2 of 30) in comparison to Group VI (p < 0.001, Mann-Whitney Test). PMID- 11199561 TI - Unhealed extraction sites mimicking TMJ pain. AB - A case of unhealed extraction sites in the mandible is described, including clinical, radiographic, and biopsy findings. The subject was treated for TMJ disease in the past but still had related signs and symptoms and facial pain. PMID- 11199562 TI - The double arch impression technique: a solution to prevent supraocclusion in the indirect restoration. AB - The literature relating to inaccuracies in the mounting of casts of semi adjustable articulators and other factors that influence the fabrication of indirect restorations is reviewed. The effects of such discrepancies often result in "high" cast restorations which require considerable adjustment clinically before definitive placement. Some solutions to "high" cast restorations are offered with indications and contraindications for their use. PMID- 11199563 TI - A review of the amalgapin technique for complex amalgam restorations. AB - For many years, large amalgam restorations have been retained with stainless steel pins or dentinal slots. In 1980, Shavell introduced the amalgapin technique for what he termed "complex" amalgam restorations. This technique consisted of preparing dentin chambers 1.0-2.0 mm deep just inside the dentinoenamel junction. As the technique became more popular, comparisons of its fracture strength to that of stainless steel pins were evaluated. This article reviews the literature concerning the amalgapin technique, examines its resistance compared to other retentive means, and discusses the method of preparation. PMID- 11199565 TI - Addressing the real future of dentistry. PMID- 11199564 TI - The oral brush biopsy: a new reason to screen every patient for oral cancer. AB - Awareness about the prevention of oral cancer by both the public and the dental professional is expected to increase significantly. This article provides timely information about the computer-assisted analysis of an oral brush biopsy, a practical and accurate aid to oral cancer screening. PMID- 11199566 TI - Tobacco is a drag on your practice. PMID- 11199567 TI - Sexual ethics in dentistry. PMID- 11199568 TI - Bonding techniques. PMID- 11199569 TI - Hypertension medications and dental considerations. PMID- 11199570 TI - Truth and lies: when patients request falsifications. PMID- 11199571 TI - Diffuse white lesions. PMID- 11199572 TI - Palatal mass. PMID- 11199573 TI - Treatment of early childhood caries: a review and case report. AB - Caries in infants and young children long has been recognized as a clinical entity and described variously as nursing caries, nursing bottle syndrome and so on. Although prolonged use of the baby bottle is believed to be associated with increased risk of caries, use of the bottle may not be the most important factor in caries development. The term early childhood caries (ECC) has been suggested because it more closely reflects the multifactorial etiologic process involved in the disease. A case of ECC treated in a general dental practice and managed under local anesthesia is reported. PMID- 11199574 TI - A comparison of parenteral and electronic dental anesthesia during operative procedures in children. AB - The effectiveness of electronic dental anesthesia (EDA) for pain control during restorative procedures was compared with local anesthesia (LA) in 108 pediatric patients aged 6-12. One tooth was treated with LA and another with EDA at the same appointment. The pain levels during restorative treatment were assessed using a color scale. Behavior also was assessed using sound, eye, and motor (SEM) scale. Although the success rate of EDA was less than that of LA, there was no significant difference between the two methods. On the other hand, 63% of the patients preferred EDA while 27.8% preferred LA. These results suggest that EDA is an effective nondrug pain control technique for amalgam restorations in primary and permanent molars for some patients. PMID- 11199575 TI - Sports dentistry in general practice. AB - The sports dentistry movement in the United States and worldwide is experiencing new momentum. Much of this is generated by general dentists working in conjunction with like-minded specialists as well as with dental hygienists, dental laboratory technicians, and dental assistants. This article explores several issues of relevance to stimulate the interest of general dentists to become involved in private practice and community service activities in sports dentistry. PMID- 11199576 TI - Early intervention to remove mesiodens and avoid orthodontic therapy. AB - Recognition of dental anomalies is essential in determining appropriate treatment for each patient. Diagnosis and assessment of mesiodens are critical in avoiding complications such as blocking the eruption of the maxillary central incisors, cyst formation, and dilaceration of the permanent incisors. Collecting data for diagnostic criteria, utilizing diagnostic radiographs, and determining when to refer to a specialist are important steps in the treatment of mesiodens. Early diagnosis and timely intervention could reduce or eliminate the need for orthodontic treatment and prevent serious complications. PMID- 11199577 TI - Current dental concepts in antibiotic prophylaxis for total joint replacement patients. AB - The subject of antibiotic prophylaxis has evoked controversy and much debate over the validity of such practice. In July 1997, the American Dental Association and American Academy of Orthopedic Surgeons issued an advisory statement concerning the use of antibiotic prophylaxis for patients with total joint replacements. A historical perspective of the subject is presented, with a review of the recommendation for total joint replacement antibiotic prophylaxis, a discussion of the new decision-making responsibility for the dentist, and medicolegal ramifications of this change. PMID- 11199578 TI - Postreplantation management of avulsed teeth: an endodontic literature review. AB - Today's dental treatment goals are directed at reducing the incidence of root resorption resulting from periodontal ligament devitalization or pulp necrosis. Although the American Association of Endodontists recommends the use of long-term therapy, short-term therapy may be utilized with confidence in well-defined clinical applications. Early final obturation with gutta-percha will increase the long-term prognosis in those cases where patient motivation is questionable or long-term follow-up prior to obturation is not possible. However, where inflammatory resorption is already present, long-term calcium hydroxide therapy is indicated. Long-term post treatment follow-up is imperative in both calcium hydroxide therapies. PMID- 11199579 TI - Smile enhancement via internal gingivectomies. AB - Periodontal plastic surgical procedures provide a wide range of techniques to improve the esthetics of the mucogingival complex. Often these procedures are prerequisites for successful restorative therapy. This article presents a simple means of enhancing a patient's smile that can be provided by simple internal gingivectomies. The technique can be provided as a stand-alone procedure or in conjunction with restorative care. The surgery is simple and predictable with virtually no postsurgical sequellae. PMID- 11199580 TI - Evaluations of the interface between amalgam and dentin with a single component dentin bonding system. AB - The purpose of this scanning electron microscope study was to observe the dentin amalgam interface after utilizing a standard restorative liner and a single component dentin adhesive. Continuous interface gaps of over 15 mu were observed in specimens containing no lining and Copal varnish. Discontinuous 5 microns gaps were observed in specimens treated with PQ1. Additionally, specimens treated with PQ1 exhibited resin interpenetration into the dentin surfaces. PMID- 11199582 TI - The complexities of cosmetics. PMID- 11199581 TI - Bonded arch bars to manage traumatic injuries to the teeth and alveolar bone. AB - A simple, rapid, painless, and bloodless method of successfully treating avulsed and partially avulsed teeth with or without associated dentoalveolar fractures is presented for management by the general practitioner in the office. It is a bonding technique with the key elements being a prefabricated malleable mesh backed arch bar in combination with any light curing composite procedure that is standard in the individual's office. PMID- 11199584 TI - Is there a doctor in the house? AB - The two cases presented deal with urgent situations experienced by persons unknown to the dentist in the area. It is likely that dentists, physicians, nurses, and other medical professionals will encounter persons in urgent need of medical attention in other venues. Certainly, it is possible for someone to experience an emergency in a ballpark, grocery store, church, or other public gathering. While these settings may not offer the advantage of a medical emergency kit, they do pose the same ethical requirement for those trained in medical management of urgent problems to step forward, identify themselves, and attempt to help the ill person. Fortunately, most non-air settings usually allow for contacting emergency medical help and prompt transport to hospitals. The public may never reach a general understanding of the extent to which doctors other than physicians are trained to handle medical emergencies. Similarly, when someone in a crowded theater yells, "Is there a doctor in the house?" he or she most likely is thinking about a physician. This does not mean that a dentist is excused from acting as a medically trained Good Samaritan. The ethical obligation of specific beneficence requires dentists to minister to the ill in medical emergencies unless a more qualified health care provider is present and identifies himself or herself. The ethical obligation of general beneficence requires dentists and other citizens to assist those in urgent circumstances whose needs do not call upon specialized knowledge or training. Fortunately, the law in this country is designed to protect those who do attempt to help those in need. PMID- 11199583 TI - Osteoporosis, alveolar bone loss, and drug development. PMID- 11199585 TI - The importance of contacts and embrasures and their effect on the periodontium. AB - Operative and restorative dentistry are challenging disciplines of dentistry. When esthetics and periodontics are added to the equation, it becomes that much more difficult for any operator to restore teeth in an ideal manner. In order to be successful and have reasonable occlusal harmony, periodontal health, and beautiful esthetics, knowledge of all of these disciplines is necessary no matter what kind of material is being placed. Continuing education, care, skill, practice, a desire for excellence, and, most of all, patience will allow any dentist to accomplish these goals. PMID- 11199586 TI - Fiber reinforced composite resin systems. AB - The Targis/Vectris and Sculpture/FibreKor systems were devised to create a translucent maximally reinforced resin framework for fabrication of crowns, bridges, inlays, and onlays. These materials are esthetic, have translucency similar to castable glass-ceramics such as OPC and Empress, and have fits that are reported to be acceptable in clinical and laboratory trials. These restorations rely on proper bonding to the remaining tooth structure; therefore, careful attention to detail must be paid to this part of the procedure. Cementation procedures should involve silane treatment of the cleaned abraded internal restoration surface, application of bonding agent to the restoration as well as the etched/primed tooth, and finally use of a composite resin. Each manufacturer has a recommended system which has been tested for success with its resin system. These fiber reinforced resins are somewhat different than classical composites, so not all cementation systems will necessarily work with them. Polishing of the restoration can be accomplished using diamond or alumina impregnated rubber wheels followed by diamond paste. The glass fibers can pose a health risk. They are small enough to be inhaled and deposited in the lungs, resulting in a silicosis-type problem. Therefore, if fibers are exposed and ground on, it is extremely important to wear a mask. Also, the fibers can be a skin irritant, so gloves also should be worn. If the fibers become exposed intraorally, they can cause gingival inflammation and may attract plaque. The fibers should be covered with additional composite resin. If this cannot be accomplished, the restoration should be replaced. The bulk of these restorations are formed using a particulate filled resin, similar in structure to conventional composite resins. Therefore, concerns as to wear resistance, color stability, excessive expansion/contraction, and sensitivity remain until these materials are proven in long-term clinical trials. They do hold the promise of minimizing tooth reduction and may be particularly useful in preserving sound tooth structure. Although not the primary intended use, an excellent application is long-term temporization, such as for patients requiring full mouth rehabilitation. The belleGlass/Connect, Ribbond, and GlasSpan materials rely on nonimpregnated polyethylene fibers which have mechanical properties inferior to Vectris and FibreKor. These fibers may be used to greater success as splinting materials, in provisional restorations, and in repair of complete and partial removable dentures. PMID- 11199587 TI - Radiolucency of the anterior mandible. Dentigerous cyst. PMID- 11199588 TI - Ulcerated palatal lesion. Ulcerating sialometaplasia. PMID- 11199589 TI - Whitening of endodontically untreated calcified anterior teeth. AB - Definitive treatment for whitening endodontically untreated anterior teeth with dystrophic calcification is provided by removing the coronal sclerotic dentin and utilizing internal and external bleaching as necessary. PMID- 11199590 TI - Combined professional and home care nightguard bleaching of tetracycline-stained teeth. AB - The effectiveness of combining in-office and at-home nightguard vital bleaching on tetracycline-stained teeth was evaluated. Grade 1 and grade 2 tetracycline stains were eliminated completely in two months by this combination approach. Grade 3 stains, the most severe, were lightened significantly with a reduction in the banding effect. The most common side effect was an increase in tooth sensitivity, especially to cold, while actively in treatment. All patients reported disappearance of the sensitivity after termination of the treatment phase. PMID- 11199591 TI - Comparison of 10% carbamide peroxide and sodium perborate for intracoronal bleaching. AB - The purpose of this study was to compare 10% carbamide peroxide to the combination of sodium perborate and water as intracoronal bleaching agents. Forty four extracted teeth were discolored in vitro. Bleaching agents were placed intracoronally to the level of the cemento-enamel junction for 12 days; solutions were replaced after four and eight days. Standardized slides were used to rank color changes; a colorimeter was used to quantify color change. After 12 days, 65% of the discolored teeth in the 10% carbamide peroxide group and 67% of the discolored teeth in the sodium perborate group had lightened to their original shade or lighter. While there was no statistical difference between the two treatments, sodium perborate was easier to use. PMID- 11199592 TI - A simple screening test for color matching in dentistry. AB - This study compared a simple and readily available shade guide color-matching test with the general industry standard test for color discrimination. This study indicates that a simple screening test for color defective vision and color discrimination skills in dentistry can be performed by matching two Vita-Lumin shade guides. Those dental office personnel who score a low number of matches in the Vita test (that is, seven or fewer correct matches) should have additional color discrimination testing and refer shade matching to other personnel with higher scores. PMID- 11199593 TI - Accessing restoration margins--a multidisciplinary approach. AB - Dentists frequently balance periodontal, restorative, and esthetic concerns that will provide adequate tooth length, ensure periodontal health, and provide biological predictability. This report discusses the current and classical literature and provides a multidisciplinary approach of predictably "accessing" the restoration margins to facilitate long-term gingival health and tooth survival. PMID- 11199594 TI - Effects of evaporation on the properties of water-based dental luting agents. AB - The most commonly used luting agents for fixed prosthodontics are water-based cements: zinc phosphate, zinc polycarboxylate, glass ionomer, and resin-modified glass ionomer. Properties were tested at baseline and after the cement liquids were allowed to evaporate for 10, 20, and 30 minutes. Viscosity, pH, contact angle, and surface tension were determined using the cement liquids only; tensile strength, hardness, film thickness, and working/setting times were determined after the cements had been mixed with the various liquids. pH decreased over 30 minutes, while viscosity, contact angle, and film thickness all increased, especially for the zinc polycarboxylate and glass ionomer cements. Changes in mechanical properties depended upon time and material. PMID- 11199595 TI - Stainless steel crown and pulpotomy: procedure and technique for primary molars. AB - The purpose of this article is to facilitate performance of the stainless steel crown and pulpotomy procedures in order to save chair time and provide a more durable and reliable final restoration for primary molars. The rationale and methods for preparing the tooth, crown selection, and placement of a stainless steel crown are included, along with alternatives for selection and technique for fabrication of more esthetic options. Medicament and tips for the pulpotomy procedure also are discussed. Information for patient education and consent regarding the procedures and their limitations is provided to complete this step by-step guide for the clinician. PMID- 11199596 TI - Systemic effects of an intraosseous injection of 2% lidocaine with 1:100,000 epinephrine. AB - The effect of a mandibular intraosseous injection of 2% lidocaine with 1:100,000 epinephrine on the heart rate and blood pressure of 20 volunteer patients was examined. Changes in blood pressure from preoperative levels were minimal and did not vary significantly at any time of measurement. The only statistically significant change in heart rate occurred immediately after the intraosseous injection (an increase of 12 beats per minute). In young healthy adults, the intraosseous injection of 1.5 mL of 2% lidocaine with 1:100,000 epinephrine resulted in a slight transient elevation in heart rate but had no significant effect on systolic or diastolic blood pressure. PMID- 11199597 TI - Ridge preservation: important buzzwords in dentistry. AB - Ridge preservations is the prevention of the 40-60% jawbone atrophy that normally takes place two to three years postextraction. It is the new paradigm in patient care that is effective, simple, and beneficial for a multitude of reasons. It is achieved by the immediate grafting of the extraction socket with or without the use of an immediate implant. The ability to not only preserve the alveolar ridge for future restorative dentistry but also to preserve and restore esthetics and prevent postoperative pain and bleeding makes this modality important for all practicing dentists. PMID- 11199598 TI - Replacement of a tooth with a fiber-reinforced direct bonded restoration. AB - Today's methods and materials for tooth replacement are multiple and varied. Modern materials now allow for highly conservative abutment preparations that can retain bonded single tooth replacement fixed prostheses. A case report is presented in which fiber reinforced with composite resin was used for placement of a three-unit fixed long-term provisional restoration, providing fracture resistance while achieving an esthetically pleasing, durable restoration. PMID- 11199600 TI - Early treatment of malocclusion: a guidance system for the general dentist. AB - Opportunities for preventive orthodontic treatment of children arise during all stages of oral growth and development. It is in the best interest of the child to achieve a state of normalcy in the neuromuscular, skeletal, and dental structures. This article provides a guide for treating malocclusion with utility archwire appliances in the mixed dentition and finishing the permanent dentition with a fully adjusted appliance. PMID- 11199599 TI - Retention of four endodontic posts cemented with composite resin. AB - Retention was compared of an active post system (Flexi-Flange), a metal passive prefabicated post system (ParaPost), a passive prefabricated burnout post system (ExactaCast) with and without grooved dentin walls, and a zirconium oxide ceramic post design (Cerapost). The Flexi-Flange with Flexi-Flow Natural cement obtained the highest retentive value of 270.4 lb. The Cerapost cemented with Universal Cement had the lowest retention value of 23.4 lb. The ExactaCast with grooved dentin walls was significantly stronger than the ExactaCast without grooving, the ParaPost, and the Cerapost. The two ExactaCast groups and the ParaPost group had higher retention than the Cerapost group. PMID- 11199601 TI - Caries detection accuracy by multiple clinicians and techniques. AB - This study compared caries detection by multiple clinicians with the accuracy of detection with Caries Detector dye. Four clinicians rated the extent of caries on 100 extracted teeth. After dye application, visual assessment of residual dye was recorded for each specimen. This was repeated after the teeth were embedded in epoxy resin and sectioned. The results indicate that although reasonably accurate overall, clinicians often disagree whether caries is present. The use of a caries detector solution may be a valuable adjunct tool to correct caries diagnosis. PMID- 11199602 TI - The dentist's role in reporting suspected child abuse and neglect. AB - While dentists are in a position to report suspected child abuse and neglect (SCAN), few reports are made by dentists. Evidence exists that dentists are not well-informed about SCAN, but even with education about SCAN, dentists continue to make few reports. Reasons for low reporting are noted. This article lists criteria which will be helpful in determining whether a traumatic injury to a child is accidental or intentional. PMID- 11199603 TI - Orthodontic relapse and the mandibular third molar: a literature review. AB - This review of the literature considers the role of the mandibular third molars in orthodontic relapse. Theories attempting to resolve the mystery of relapse following orthodontic treatment are presented. While the literature supports the conclusion that there are valid reasons to remove third molars, it does not greatly support prophylactic removal and removal to avoid orthodontic relapse. PMID- 11199604 TI - Crisis management. PMID- 11199606 TI - Third-party treatment. PMID- 11199605 TI - Amalgam restorations. PMID- 11199607 TI - Early removal of mesiodens. PMID- 11199608 TI - New drug approvals in 1999. PMID- 11199609 TI - Ethical duties when patients make suspicious narcotic requests. AB - Practicing dentists are likely to be familiar with the prospect of patients who request controlled substances for doubtful indications. Torn between ethical obligations of beneficence and nonmaleficence, the dentist may be uncertain whether to prescribe a medication with the intention of alleviating pain or to refuse the prescription due to concerns related to chemical dependency, underlying emotional illness, or ulterior motives on the part of the patient. Pharmaceutical choices often do not provide a mechanism for sidestepping this dilemma as chemically dependent patients may be quite sophisticated in their knowledge of drugs and the ways in which to couch their requests. Dentists have an ethical obligation to move beyond simply refusing prescriptions for patients suspected to be chemically dependent; they should sensitively discuss the issue with these patients and be prepared to offer referral for intervention. However, dentists must always be open to the possibility that a particular patient's assertion of chronic physical pain may be of complex origin. When this is the case, appropriate treatment is essential and may involve referring the patient to others with specialized skills. Dentists should not withhold pain medication from patients with uncontrolled pain in the final stages of life. PMID- 11199610 TI - Rough buccal mucosa. PMID- 11199611 TI - Bilateral white buccal mucosa. PMID- 11199612 TI - Location of incisal edge position for esthetic restorative dentistry. AB - Restorative dentistry means just that--changing the position and morphology of teeth (when indicated) to restore the patient to a functional and esthetic occlusion. The first step considers the mandibular incisal edge position. Following that choice, the maxillary anterior teeth are evaluated for position against the lips and with the rest of the dentition, particularly the mandibular incisors and canines. When the three major determinants of incisal edge position (occlusion, phonetics, and esthetics) are used to place the anterior teeth where they will function best, all cases have the potential for a more enduring esthetic success. PMID- 11199613 TI - The longevity of resin-based composite restorations in posterior teeth. AB - A survey of published prospective and retrospective studies examining the longevity of posterior resin-based composite and amalgam restorations confirms the need for clinical judgment in materials selection. PMID- 11199614 TI - Retention strength of tin plated gold inlays bonded with two resin cements. AB - Research has shown bonding of restorations to tooth structure to enhance retention of the restoration to increase the fracture resistance of the tooth, and to reduce microleakage. Resin cements have superior physical properties to traditional cements such as zinc phosphate. The purpose of this study was to compare the retention of gold inlays luted with two resin cements to that of those luted with zinc phosphate cement. PMID- 11199615 TI - Effect of prebonding procedures on shear bond strength of resin composite to pressable ceramic. AB - Low bond strength between tooth structure and restorative ceramic material is a major cause of ceramic fractures or failures. Prebonding measures performed on pressable ceramic material were evaluated and the different shear bond strengths obtained by each method were tabulated. The three individual groups were subjected to 9% hydrofluoric (HF) acid gel for 0, 1, and 5 minutes. The different acid-etched time groups were chemically treated with silane coupler alone, silane coupling agent with bonding agent, and bonding agent alone. The silane coupling agent produced the highest bond strength between the composite structure and the pressable ceramic restorative material. High bond values were achieved by etching the porcelain for one minute. The use of the silane coupling agent with a one minute 9% HF acid etch yielded the greatest bond strength. PMID- 11199616 TI - Comparison of composite resin-to-porcelain bond strength with three adhesives. AB - Three resin-based adhesives were evaluated for suitability for porcelain repair with composite resin, as measured by shear bond strength of attachment. Photo Bond and SE Bond were associated with significantly greater shear bond strengths than their respective controls at both time periods investigated. Single Bond did not have shear bond strengths greater than its control and its values were significantly lower than those obtained with the other resins. PMID- 11199617 TI - Treatment of endodontic perforations by guided tissue regeneration. AB - Case reports of mandibular molars with iatrogenic perforations are presented. Such perforations have been treated with internal amalgam repair or by surgical intervention. However, the potential exists for tissue migration and pocket formation. The use of guided tissue regeneration as a barrier for apical migration is beneficial in surgical treatment of perforations. Follow-up examination of perforated teeth treated with resorbable barriers showed successful repair. Results obtained with this technique offer the possibility of a successful repair for an otherwise hopeless complication of endodontic therapy. PMID- 11199618 TI - Periodontitis--the risks for its development. AB - The relationships between periodontitis and systemic disease and conditions, environmental factors, and behavioral influences are evolving rapidly. Success in preventing and treating periodontal diseases may well rest to a large extent on our understanding of the relevant influences which may exacerbate and perpetuate the disease process. As researchers work to clarify these relationships, we as practitioners must continue to alter our treatment in the best interests of the patient's overall health. The impact of recent findings on the development and progression of periodontitis relevant to diabetes mellitus, HIV, genetic susceptibility, smoking, stress, and osteoporosis is reviewed. PMID- 11199619 TI - Evaluation of ergonomic dental stools through clinical simulation. AB - Work-related musculoskeletal pain occurs commonly within the dental community. Three stool designs were utilized in this study: a standard dental stool, a stool with dual arm supports, and a stool with dual arm supports and chest support. Electromyographic data from four muscle groups were collected on 13 clinicians during a simulated crown preparation procedure. Clinical simulation suggests that a potential musculoskeletal benefit to the clinician exists through utilization of dental stool designs which incorporate static arm supports. PMID- 11199620 TI - Acupuncture/acupressure to treat gagging dental patients: a clinical study of anti-gagging effects. AB - Noninvasive methods advocated by some clinicians are not very successful in dealing with patient gagging, while sedation approaches run the risk of the patient aspirating foreign bodies. The P-6 Neikuan acupuncture point, located on the wrist, has been used in the Far East for thousands of years for its anti nausea and anti-anxiety properties. In the West, it is the acupuncture point most studied. Only recently has interest been shown in the P-6 point for its possible anti-gagging effect. The anti-gagging effect of P-6 stimulation is documented in this article. The P-6 point has remarkable anti-gagging effects if stimulation is applied correctly. Clinicians may apply thumb pressure at the P-6 point to achieve some effect, although this is not as effective as acupuncture. Nevertheless, a substantial percentage of gagging patients would be able to go through dental procedures without gagging when the P-6 point is stimulated. PMID- 11199621 TI - Attachment loss associated with the presence of a tongue bar: a case report. AB - Recent reports demonstrate that tongue bars can cause damage to the dentition. The first known report of attachment loss associated with the presence of a tongue bar is described. PMID- 11199622 TI - Tuberculous ulcer of the tongue as presenting feature of pulmonary tuberculosis and HIV infection. AB - Tuberculosis (TB), once a lethal disease, has shown a decrease in incidence with improved public health measures and availability of antituberculous drugs. But with the advent of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS), it has re-emerged alarmingly as an opportunistic infection in immunocompromised patients. Lungs are the most commonly affected organs and involvement of the oropharyngeal region in TB is very rare. Two cases of TB manifesting as ulcer of the tongue are reported here. Interestingly, both of these cases were reported within a span of six months and both of the patients were in their early thirties. A primary diagnosis of both pulmonary TB and HIV sero-positivity was made after the diagnosis of the oral TB ulcer. PMID- 11199623 TI - Cancer awareness and dentistry. AB - Dentists have the prime responsibility to screen for cancer of the oral cavity. A history, head and neck examination, and intraoral examination including the pharynx should be performed on all new dental patients and at all recall appointments. Patients with lesions that appear clinically to be cancer are best managed by immediate referral to a head and neck surgeon or cancer treatment center for biopsy and treatment. Lesions that may be cancerous can be biopsied by the general dentist or oral surgeon. Dentists also should be prepared to talk with patients at risk for cancer of the breast, colon, cervix, prostate, and skin about the advantages and disadvantages of being screened. These patients should be encouraged to talk with their primary care physicians about being screened for cancer. PMID- 11199625 TI - Seniors discounted. PMID- 11199624 TI - Potential fear-provoking patient experiences during treatment. AB - During a four-month period in 1998, 250 new patients arriving at the General Dentistry Clinic of Tufts University School of Dental Medicine were asked to complete a questionnaire regarding behavior by dental professionals and its effect on dental care. Surveys were returned by 121 women and 82 men, who evaluated seven behaviors from five previously determined categories of anxiety. Age and gender were the only factors considered in analyzing the results. The data suggest that dentists often may exhibit a variety of negative behaviors and attitudes. These can cause increased levels of concern in patients and may act as fear-provoking stimuli, leading to increased fear and avoidance of dental treatment. PMID- 11199626 TI - Elder abuse: society's forgotten issue. PMID- 11199627 TI - The top 50 prescription medications dispensed in pharmacies in 1999. PMID- 11199628 TI - The dentist's role in bereavement support. AB - An aging population that is retaining more dentition and an increasing number of persons affected by terminal illnesses have resulted in dentists encountering dying patients and patient deaths with increasing frequency. These events call upon dentists and their staffs to provide support for the terminally ill and for survivors of the deceased. Dentists are effective in providing bereavement support and survivors benefit greatly from it. However, this type of support is stressful for dentists and many report the need for more formal education in this area. The ethical basis for dealing effectively with a dying patient's need for open and honest discussion derives from the obligations of the doctor-patient relationship. These ethical requirements carry over to providing some level of bereavement support for the surviving loved ones of the deceased and address the professional duties of compassion and care. Sending a sympathy card with a personal note, attending the patient's funeral, or making a follow-up telephone call to the patient's survivors are all appropriate, beneficial, and appreciated. PMID- 11199629 TI - Esthetic and functional reconstruction of the geriatric patient. AB - Esthetics is not only for the young. People at every age want to look their best and have a confident and beautiful smile. Generally speaking, restored senior citizens become very appreciative of the care they receive, refer others like themselves, and, most importantly, have a renewed self-worth and can continue to interact socially for many years. PMID- 11199630 TI - Impression materials: basic properties. PMID- 11199631 TI - Mulifocal intraosseous pathoses. PMID- 11199632 TI - Multiple radiolucencies and loose teeth. PMID- 11199633 TI - Spectrum of care treatment planning: application of the model in older adults. AB - A model for treatment planning is presented to help emphasize the most important elements of the clinical decision-making process for older adult patients. The patient's concerns and needs in the domains of function, symptoms, pathology, and esthetics are the central elements of the process. With sophisticated assessment methods and creative interventions, the dentist can work with each patient to identify and successfully address his or her needs and concerns. This model is applied to two clinical cases which illustrate the importance of considering innovative treatment plans, even when the patient is advanced in years. PMID- 11199634 TI - Aging and oral health for the 21st century. AB - Americans' oral health, along with their life expectancy, has improved dramatically during the 20th century. The 21st century offers dental professionals the opportunity to help patients maintain their oral health for a lifetime. This article describes trends in health and wellness among older adults that will affect use of dental services; reviews risk factors such as chronic diseases, medications, and nursing home placement that will increase oral diseases in older adults; and concludes with opportunities for dental leadership to improve the oral health of aging Americans. PMID- 11199635 TI - Restorative considerations in the dental treatment of the older patient. AB - The older person and his or her dentition will have a clinical presentation and a reaction to treatment that is influenced by his or her unique blend of aging and disease processes. Changes seen in enamel, dentin, pulp, and cementum of the older patient are described in terms of their causes and the impacts of the changes on clinical presentation and treatment choices. PMID- 11199636 TI - Management of systemic diseases and chronic impairments in older adults: oral health considerations. AB - This paper reviews the most common systemic diseases and chronic conditions among the elderly. It provides an overview of the adverse effects these conditions and their treatments have on oral health and function and summarizes some treatment methodologies to be employed in the dental office. PMID- 11199637 TI - Providing general dentistry for people with disabilities: a demographic review. AB - In the mid-1990s, approximately 54 million American people had some level of disability, including 26 million who had a severe disability. In addition, more than three-quarters of individuals with mental retardation/developmental disabilities were deinstitutionalized during the past 30 years and now reside in our communities, relying upon community practitioners for needed services. This review is provided to make dental practitioners aware of the magnitude and dimensions of the situations in which persons with special needs require their services. PMID- 11199638 TI - Parkinson's disease: an update for dentists. AB - One of the diseases that will afflict the growing number of elderly American dental patients is Parkinson's disease, yet few dental articles and textbooks address the condition. This article reviews the clinical and diagnostic features, pathophysiology, management, and dental concerns in patients with Parkinson's disease who undergo dental care. PMID- 11199639 TI - Analgesic prescribing patterns in a group of dentists. AB - Dentists have an increasing number of analgesic agents available to enable them to deal with pain relief. Each of these agents has advantages tempered by undesirable side effects. Five years ago the authors conducted a survey of dentists to compare analgesic prescribing habits. A follow-up study was conducted to ascertain any changes in analgesic therapy prescribing habits. It was determined that most dentists prefer to prescribe on an as-needed basis rather than by the clock. New drugs in the marketplace have not changed the approach of dental practitioners in handling pain management; similarly, prescription writing patterns have not changed appreciably in the last five years. More restraint probably could be used in prescribing narcotic agents. PMID- 11199640 TI - Early creeping attachment after frenectomy: a case report. AB - An abnormal labial frenutomy is capable of causing retraction of gingival margins, formation of diastema and inhibition of lip and tongue movements. When aberrant frenula are present traditional frenectomy procedures are very successful. Often mucogingival procedures are needed to correct the defects that result from harmful frenum pulls. In this case presentation, an aberrant frenum was diagnosed to be associated with an area of recession on a mandibular left central incisor. Surgery was planned as a staged approach. The first phase of care was a simple frenectomy. A follow-on procedure consisting of a connective tissue graft for root coverage was planned. After only four weeks of healing from the frenectomy, creeping attachment of 1.0 mm was appreciated and the patient was able to avoid the secondary corrective surgery. PMID- 11199641 TI - Endodontic radiographs: realities and illusions. AB - Several case reports show how, on occasion, radiographs fail to disclose important realities. The illusions that are presented radiographically have the potential to misdirect diagnosis and treatment as well. PMID- 11199642 TI - Biomechanically-induced dental disease. AB - Malocclusion, as an etiological agent in dental disease, is among the most controversial subjects in dentistry. Bruxism has been blamed on stress and many other nondental factors. A biomechanical mechanism that serves as a contributing factor to stimulate tooth clenching and grinding is defined and used to identify the 12 common dental symptoms caused by tooth clenching and grinding. A method is proposed through which the practitioner can link the observable dental signs with the biomechanical factors for accurate diagnosis and appropriate treatment, preferably at an early stage before the damage becomes severe. PMID- 11199643 TI - Submandibular gland sialolithiasis: a case report. AB - Most cases of sialolithiasis of the submandibular duct are resolved by an intraoral surgical approach. This case is unique in that by virtue of the sialolith's proximity to the hilum of the gland, it was more prudent to perform an excision of the entire gland through an extraoral approach. PMID- 11199644 TI - Microleakage study of flowable composite resin systems. AB - The purpose of this in vitro microleakage study was to evaluate four low viscosity composite resin systems. Each resin system included the corresponding bonding agent for each respective flowable composite. A hybrid material was used as a control. A total of 75 noncarious, freshly extracted human teeth were prepared with a Class 5 occlusal preparation and a gingival preparation at the cementoenamel junction. The materials were inserted according to the manufacturers' recommendations using the single-component bonding agent for each system. Teeth were thermocycled 800 times between 5 degrees C and 55 degrees C with 30-second dwell times. The teeth were then coated with nail polish 1 mm short of the restoration, placed in a basic fuchsin dye for 24 hours, and sectioned with a diamond wheel. Enamel and dentin/cementum margins were analyzed for microleakage on a scale of 0 (no leakage) to 3 (axial wall). Results were evaluated with the Fisher's exact test. The results of the study indicate that there was no leakage at the enamel margin of any restorations. No statistically significant differences in microleakage were found in dentin/cementum margins among the samples in the experimental group or between the experimental group and control group. The results indicate flowable composites demonstrate resistance to microleakage in both enamel and cementum/dentin margins similar to TPH hybrid composite. PMID- 11199645 TI - A final OSHA tuberculosis standard: are mandatory government regulations necessary? PMID- 11199646 TI - Creeping attachment: autogenous graft vs dermal matrix allograft. AB - For many years, free autogenous grafts have been used as a method of gaining keratinized tissue around teeth with mucogingival problems. Creeping attachment using autogenous graft material has been actively studied. In addition, biocompatible, acellular connective-tissue material has recently been used as an alternative to free gingival grafts to increase the zone of keratinization. This report presents a patient with bilateral mucogingival defects in the canine and premolar areas. The patient received an autogenous graft on one side and a dermal matrix allograft on the contralateral side. Creeping attachments were measured and compared at 3 months and 12 months after surgery. After 12 months of healing, an average of 1.23 mm of creeping attachment was measured on the free gingival graft side and 0.96 mm of creeping attachment was measured with the dermal matrix allograft. PMID- 11199647 TI - Subgingival restorations with resin ionomer: a periodontal alternative. AB - The successful use and placement of subgingival resin-ionomer restorations in both anterior root and molar furcation defects are demonstrated in this article. Sustained tissue health and minimal probing depths at the surgical site demonstrate clinical success. These case reports illustrate the continued success of alternative treatment procedures for restoring subgingival mechanical root or periodontal lesions. PMID- 11199648 TI - Resin-based luting cements. PMID- 11199649 TI - Patient and dentist satisfaction with a computerized local anesthetic injection system. AB - The fear of dental injections is common among dental patients. Many approaches to reducing this fear of injections and improving local dental anesthesia delivery have been tried in the last few decades. One approach is the use of a computerized or electronic local anesthetic system. This study surveyed dentist and patient satisfaction when local dental anesthesia was delivered with a computerized delivery system. The patients and dentists were both satisfied with the effectiveness of the anesthesia. The patients were satisfied with the level of comfort with the injections. This was particularly true when compared to their previous anesthetic injections. Although the dentists were very satisfied with the performance of the anesthetic delivery system and the anesthesia itself, they did not, in general, choose to use the system in everyday practice. Possible reasons for this within the context of this study are discussed. PMID- 11199650 TI - Replacement of the incisal angle in aged dentition. PMID- 11199651 TI - Opportunities in dental, oral, and craniofacial research. PMID- 11199652 TI - Orthodontic tooth extrusion as an adjunct to periodontal therapy. PMID- 11199653 TI - Strengthening mechanisms of current dental porcelains. AB - Dental porcelains have a high glass content, which provides the translucency necessary for esthetic restorations. Because glasses are brittle, they fail under tension or bending by the propagation of preexisting flaws (e.g., scratches, porosities). Several approaches that are based on impeding the propagation of flaws have been used to strengthen dental porcelains, including bonding to metals, adding microcrystalline phases, and surface treatments (i.e., polishing, ion exchange, hydration). Through these methods, porcelain systems are used routinely for all-ceramic anterior restorations; however, porcelain-fused-to metal restorations remain the most reliable for posterior applications. PMID- 11199655 TI - Ceramic design concepts based on stress distribution analysis. AB - This article discusses general design concepts involved in fabricating ceramic and metal-ceramic restorations based on scientific stress distribution data. These include the effects of ceramic layer thickness, modulus of elasticity of supporting substrates, direction of applied loads, intraoral stress, and crown geometry on the susceptibility of certain restoration designs to fracture. PMID- 11199654 TI - Approaches for intraoral repair of ceramic restorations. AB - Ceramic-based restorations are an important part of a dentist's armamentarium for durability and esthetics. Because of the brittle nature of ceramic materials, these restorations have the potential to fracture. Repairing ceramic-based restorations can increase the clinical longevity of failed restorations and offer the dentist and patient a cost-effective alternative to replacement. Newer porcelain repair systems show excellent adhesion durability of resin-based composites to the fractured ceramic and exposed metal surfaces. This article reviews the basic principles of ceramic repair and details the use of five intraoral porcelain repair systems. PMID- 11199656 TI - To silanate or not to silanate: making a clinical decision. AB - Etched porcelain-bonded restorations have become the treatment of choice for the esthetic restoration of anterior teeth. The bond strength of composite resin to properly etched and silanated porcelain exceeds the cohesive strength of porcelain. Although bonding to enamel is accomplished by only etching the surface to create micromechanical retention, bonding to porcelain is achieved both mechanically through etching porcelain and chemically through the use of a silane coupling agent. Literature supports silanization of porcelain, which provides a more reliable bond than etching with hydrofluoric acid only, although the combination of both are recommended. This article discusses the importance of proper silanization of porcelain in obtaining a durable and reliable resin composite bond with porcelain. PMID- 11199657 TI - Early detection of caries. PMID- 11199658 TI - Restorative options for malformed permanent molars in children. PMID- 11199659 TI - Relationship of the periodontium to impression procedures. PMID- 11199660 TI - A simplified approach to optimizing denture stability with lingualized occlusion. AB - Occlusal prematurities are destructive and destabilizing influences in complete dentures. Unless denture bases are adequately and evenly stabilized, it is virtually impossible to properly equilibrate the occlusion. One reason is that all artificial teeth in a denture unit are physically bound into a single denture base and literally act as a single tooth. Therefore, a single point of occlusal prematurity disrupts the entire denture occlusion and negatively affects the denture base stability and retention, preventing proper equilibration. This article describes a step-by-step approach using an intraoral central bearing point tracing device and lingualized occlusion to achieve an effective and simplified equilibration. PMID- 11199661 TI - Additive analgesia without opioid side effects. AB - Postoperative pain control is often inadequate because of insufficient pain relief or unacceptable side effects. Nonsteroidal antiinflammatory drugs (NSAIDs) are very efficacious for pain of dental origin, but their ceiling of efficacy does not result in greater peak analgesia if the dose is raised beyond recommended limits. Switching to an opioid combined with acetaminophen or aspirin does not result in greater analgesia, but increases the incidence of side effects such as drowsiness and nausea. Combining NSAIDs with opioids has been largely unsuccessful and still results in opioid side effects. The combination of NSAIDs with acetaminophen holds promise for greater analgesia than either drug alone, but without the increased side effects associated with opioids in ambulatory dental patients. PMID- 11199662 TI - Ridge preservation of dentition with severe periodontitis. AB - Severe loss of alveolar bone height and width can occur following the removal of teeth with advanced periodontitis. This compromise of the alveolar bone can limit the options available for achieving an acceptable dental restoration. Two case reports are presented of alveolar ridge augmentation after tooth removal and before implant placement using bone grafting and a biodegradable membrane. The resultant alveolar ridges in both patients were adequate for the placement of dental implants. PMID- 11199664 TI - Report on a unique polymer barrier system. PMID- 11199663 TI - Autogenous bone harvest and bone compacting for dental implants. AB - The long-term success of a dental implant depends on having or creating an adequate amount of autogenous bone. An instrument is described that conserves the drilled bone during implant preparation, as well as during bone-block graft preparation. Compression of the autogenous bone is performed within the instrument. Also, a simple particulate bone harvest technique from the anterior mandible is offered. The value of a compacted cake of corticocancellous autogenous bone is discussed for dehiscence/fenestration defects as well as for sinus lift bone grafting. PMID- 11199665 TI - Packable composites for posterior clinical applications. PMID- 11199666 TI - Periodontal disease: link to cardiovascular disease. AB - Poor oral hygiene that leads to dental infections could contribute to adverse medical outcomes such as cardiovascular disease. Twelve studies of varying degrees of design rigor have associated dental conditions, such as periodontal disease, missing teeth, and edentulousness, with either coronary heart disease or a cerebral vascular accident. Six of the studies were longitudinal so that the demonstration of the oral health parameters as significant predictors of the cardiovascular event would elevate the dental parameter to the status of a risk factor. Because dental diseases (especially periodontal disease) are treatable, the dental component is a modifiable risk factor; therefore, maintaining good oral health should receive the highest priority for a healthy life. PMID- 11199667 TI - Using a system of diagnosis and treatment planning to reduce stress. AB - Because a thorough system of treatment planning was used, the dentist was able to change the patient's smile and discuss potential problems with the patient before treatment. This discussion allowed the patient and dentist to proceed with treatment knowing that any problems would be dealt with if they arose. The work up of the case also made it easier for the laboratory to know exactly what outcome the dentist and patient were expecting. This enhanced communication allowed the case to proceed with a minimum of stress for everyone. PMID- 11199668 TI - Simultaneous and staged approaches for guided bone regeneration. AB - Two approaches for obtaining bone augmentation around implants by guided tissue regeneration are described. In the first, bone is regenerated simultaneously with implant placement, which is a time saving tactic. However, when initial stability of the implant cannot be obtained because of insufficient bone volume, a staged approach must be considered. In the staged approach, the bone is augmented and the implant is inserted later. The staged approach offers improved primary stability, allows the implant to be inserted in mature bone, and enables examination of the newly augmented bone before a decision is made whether or not to use it as an implant site. Two case reports are presented which illustrate the approaches. PMID- 11199669 TI - An overview of delayed passive eruption. AB - The condition of delayed or altered passive eruption exists in adults when the gingival unit remains positioned on the convex prominence of the enamel rather than at or in proximity to the cementoenamel junction. Treatment protocol is based on periodontal, esthetic, and prosthetic considerations. In addition, the gingival/osseous relationship becomes important for proper diagnosis and treatment. The purpose of this article is to increase awareness of the pathognomonic signs and symptoms of delayed passive eruption so that appropriate treatment can be rendered. PMID- 11199670 TI - Nontray whitening. PMID- 11199671 TI - Comparison of sensitometric and diagnostic performance of two films. AB - The sensitometric properties of Kodak Ektaspeed Plus and Flow E-speed film as well as their diagnostic efficacy for detecting proximal surface caries were compared. Flow and Kodak E-speed films were exposed and processed according to American National Standards Institute and American Dental Association (ADA) specifications, and film speed, contrast, and density of base plus fog were measured. Additionally, 80 premolar and molar teeth were imaged and their proximal surfaces scored by 12 dentists for the presence of caries. The actual depth of the caries was determined by microscopic examination of the teeth after sectioning. Kodak Ektaspeed Plus and Flow E-speed films, although labeled E-speed by the manufacturers, are both slow F-speed films. They have comparable base plus fog densities and comparable contrast curves. Dentists detected carious lesions equally well using both film types. The sensitivity, specificity, accuracy, and receiver operating characteristic area for detecting enamel and dentinal caries were not significantly different between the two films. Kodak Ektaspeed Plus and Flow E-speed films both meet or exceed the ADA performance specifications in terms of sensitometric properties. Both offer equal diagnostic utility for detecting caries. PMID- 11199672 TI - Using calcium sulfate in guided tissue regeneration: a recipe for success. AB - The concept of guided tissue regeneration was first introduced in the literature more than 20 years ago. Since then, the concept has evolved to include different materials and different techniques. This article describes the technique of using calcium sulfate as a component of a composite graft and as a resorbable barrier. Its unique biological and clinical advantages are described. PMID- 11199673 TI - Defect morphology: effects on regenerative predictability and membrane selection. AB - In clinical experience, guided tissue regeneration has been associated with complications, which include membrane exposure. The maintenance of a stable blood clot under the membrane is key to a successful regenerative outcome. This requires adequate membrane stabilization, tension-free suturing, and maintenance of a good vascular supply to the defect. Careful selection of defects after a thorough periodontal evaluation and modification of surgical techniques from those used for conventional resective procedures can lead to predictable outcomes for guided tissue regeneration. PMID- 11199674 TI - Using absorbable collagen membranes for guided tissue regeneration, guided bone regeneration, and to treat gingival recession. AB - This article reviews the role of barrier membranes in guided tissue regeneration (GTR) and guided bone regeneration (GBR), including the advantages of using absorbable barrier membranes in GTR and GBR and the unique properties of collagen membranes. The indications and contraindications for using collagen membranes for these procedures are examined, and successful cases are presented. Finally, the role of collagen membranes in the future of regenerative therapy is considered. PMID- 11199675 TI - Clinical software & electronic charting--essential tools. PMID- 11199676 TI - Is there a light at the end of the tunnel? PMID- 11199677 TI - Implant site development using guided bone regeneration techniques. PMID- 11199678 TI - New advances in local anesthesia. AB - In dentistry, local pain management is a critical component of patient care. When efforts to achieve local anesthesia are unsuccessful, the resulting stress for both the patient and practitioner can be significant. This Forum has reviewed new technologies that are reported to increase the probability of a favorable outcome with local anesthesia. Like all new techniques, devices, and drugs, there is a learning curve that must be mastered. However, the potential benefits of the new devices and techniques available in local anesthesia broaden the practitioners' choices. There may not yet be a "magic bullet" in local anesthesia, but the advances reviewed here hold great promise. Our participants seem to agree that predictable local anesthesia will always require a thorough understanding of the broad range of devices, techniques, and drugs available and a commitment by the dentists to use them wisely. PMID- 11199679 TI - Soft-tissue maintenance techniques: optimal esthetics without periodontal plastic surgery. PMID- 11199680 TI - Practice management software: reading the fine print. PMID- 11199681 TI - Trigeminal neuralgia--an update. AB - The purpose of this article is to give a concise review of the diagnosis and management of trigeminal neuralgia (TN), with particular emphasis on idiopathic TN and symptomatic TN. The clinical characteristics of both conditions are presented, and the suspected underlying etiologies are discussed. Because it is crucial for clinicians to be able to rule out pain unrelated to TN, a list of differential diagnoses is presented. The authors stress that the diagnosis of TN is made clinically; however, diagnostic imaging may be indicated in selected cases. Current pharmacological and neurosurgical options for the management of TN are discussed in detail. In light of the popularity of unconventional treatments in the United States, the value of acupuncture and homeopathy, both of which have been suggested by some authors for the treatment of TN, is critically assessed. PMID- 11199682 TI - Emdogain: evidence of efficacy. AB - This article addresses the use of enamel matrix proteins (Emdogain) to enhance regeneration of the periodontium. Information regarding the role of Emdogain to induce cementogenesis and histologic evidence in animals and humans that it can initiate regeneration of diseased sites are discussed. Several clinical trials have indicated that Emdogain plus modified Widman flap surgery provide a better result than the surgery alone. Several other investigations have indicated that flap surgery plus Emdogain or a bioabsorbable membrane achieve similar results. However, this latter finding needs further validation. Clinical examples of successful therapy with Emdogain are presented. PMID- 11199683 TI - Restorative dentistry using a multidisciplinary approach. AB - Multidisciplinary treatment was essential for this patient to optimally manage the occlusion and missing teeth. When the space distribution was completed, ridge management procedures for pontic site development were accomplished. The final restorative treatment required was actually minimized to a 7-unit fixed partial denture. It was apparent the multidisciplinary treatment was essential to predictably manage this patient by decreasing risk and ensuring a long-term strategy for enhanced patient satisfaction. PMID- 11199684 TI - Using the PerioChip in treating adult periodontitis: an interim report. AB - Multicenter clinical trials have established that the adjunctive use of the subgingival controlled release of chlorhexidine, in the form of the PerioChip, significantly reduces pocket probing depth, improves probing attachment levels, and reduces bleeding on probing compared to scaling and root planing alone, for periods up to 9 months. The purpose of the present study was to report on the adjunctive use of the PerioChip for the long-term management of adult periodontitis for 2 years. A total of 836 patients with adult periodontitis from private dental offices were recruited into the trial. This interim report is on the first 72 patients to have completed the 2-year study. Treatments included initial definitive therapy followed by PerioChip placement in pocket sites with a pocket probing depth of > or = 5 mm after 1 month. Subsequently, the patients received routine periodontal maintenance therapy together with the placement of a PerioChip in pockets with pocket probing depths > or = 5 mm every 3 months. Results indicated that there was a continuous decrease in pocket probing depth over the 2 years (1.26 +/- 0.77 mm). This decrease in pocket probing depth was marked over the first 9 to 12 months, and then appeared to be less marked over the next 12 months. At 2 years, 60% of the patients had at least 2 pockets showing a reduction of 2 mm or more, and only 10% of the patients showed no change or increased pocket probing depth. The results indicate that adjunctive PerioChip use is a clinically effective treatment option for dental professionals and their patients for the long-term management of adult periodontitis. PMID- 11199685 TI - Ultralight composite resin for whitened teeth: case reports. PMID- 11199686 TI - The periodontal-medical risk relationship. PMID- 11199687 TI - Secondary caries and restoration replacement: an unresolved problem. AB - This article reviews the prevalence and main causes of restoration failure and replacement. It then focuses on secondary caries, its histopathology, etiology, difficulties in diagnosis, and prevention and remineralization possibilities. This article concludes that although secondary caries is still the main reason for restoration replacement, the development of new technologies for detecting and monitoring these lesions at an early stage should allow for testing new interventions to arrest or remineralize these lesions, which would delay the need for re-restoration. PMID- 11199688 TI - Using the Master Diagnostic Model to enhance restorative success in implant treatment. AB - Pretreatment planning is the most important step for definitive diagnosis and treatment. Often, the pretreatment phase consists of a radiograph and study models without confirmation of the patient's jaw relationships and how they affect dentition. The Master Diagnostic Model waxing technique confirms jaw relationships and determines which hard and soft tissues should be replaced on the articulated models. In addition, this technique allows the patient to observe and comprehend what the final result will resemble. Documentation of patients with various clinical situations using the Master Diagnostic Model technique is presented. PMID- 11199689 TI - Preemptive vs preventive analgesia: which approach improves clinical outcomes? AB - Administering a drug that blocks painful (nociceptive) input from entering the central nervous system before a surgical procedure attenuates the development of changes that manifest as increased pain at later time points. Clinically, this strategy predicts not only less pain during the initial postoperative period, but also lowers the intensity of pain during the days after the procedure. By lessening pain during recovery, fewer analgesics are consumed, which results in fewer adverse drug reactions (i.e. side effects) complicating the postoperative course and delaying the patient's return to normal activities. The patient can be assured that the postoperative pain associated with the procedure will be minimized, thereby decreasing postoperative apprehension, increasing patient motivation for enduring the procedure, and enhancing the probability of a smooth postoperative course. The adaptation of this method as a standard clinical practice has been delayed by controversy over whether the pharmacological intervention should be administered before the surgical event (preemptive analgesia), before pain onset (preventive analgesia), or by repeat administration over the expected postoperative course. Evidence reviewed in this article supports all of these approaches for decreasing the development of central sensitization, attenuating postoperative pain, decreasing analgesic consumption, and enhancing recovery. PMID- 11199690 TI - Antiseptics and antibiotics as chemotherapeutic agents for periodontitis management. AB - Antiseptics and antibiotics have both been used to treat periodontal infections. Although antiseptics and antibiotics have antibacterial properties, they represent two distinct and separate categories for agents. Sustained-release delivery systems have made it possible to use these agents to augment the beneficial effects of mechanical periodontal therapy. This article provides an overview of antiseptics and antibiotics, and compares and makes recommendations for the use of these agents in periodontics. The objective of this article is to provide an understanding of the distinct properties of each of these categories of antimicrobial agents. PMID- 11199691 TI - Esthetic posterior tooth replacement using a fiber reinforced bridge. PMID- 11199692 TI - Practical antimicrobial periodontal therapy. AB - Specific pathogenic bacteria play a central role in the etiology and pathogenesis of destructive periodontal disease. Under suitable conditions, periodontal pathogens colonize the subgingival environment and are incorporated into a tenacious biofilm. Successful prevention and treatment of periodontitis is contingent on effective control of the periodontopathic bacteria, which is accomplished with professional treatment of diseased periodontal sites and patient performed plaque control. Subgingival mechanical debridement, with or without surgery, constitutes the basic means of disrupting the subgingival biofilm and controlling pathogens. Appropriate antimicrobial agents that can be administered systemically or via local delivery may enhance eradication or suppression of subgingival pathogens. Microbiological testing may aid the clinician in the selection of the most effective antimicrobial agent or combination of agents. Understanding the benefits and limitations of antibiotics and antiseptics will optimize their usefulness in combating periodontal infections. PMID- 11199693 TI - Direct-indirect heat-cured occlusal splint fabrication for a patient with limited mouth opening. AB - There are several conditions that can cause limited mouth opening. Recent literature on some of the most common conditions is discussed in this article. The difficulty in making alginate impressions may prevent indirect laboratory fabrication of heat-cured occlusal splints for patients with limited mouth opening. This article presents a combined direct-indirect technique for fabricating a heat-cured laboratory-processed maxillary occlusal splint in a case where making a mandibular alginate impression would have been extremely difficult. An extra-hard baseplate wax interocclusal record was used as a template for occlusal splint fabrication. The wax record was fitted to the maxillary side, then the mandible was gently manipulated to provide light imprints of the opposing teeth. The wax record provided the therapeutic vertical dimension as well as the therapeutic interocclusal relationship for the occlusal splint. The wax record was seated and sealed to the maxillary cast and modified on the palatal and facial aspects for the appropriate splint shape. The splint was processed using clear heat-cured acrylic resin. It required minimum adjustment on delivery. This procedure spared the patient from having a lower impression, which would have been required for the traditional laboratory-made occlusal splint. Increased adjustment time and excessive exposure to unoccurred acrylic resin, which would have occurred with direct intraoral fabrication, were minimized or eliminated using this technique. PMID- 11199694 TI - A guide to polishing direct composite resin restorations. PMID- 11199695 TI - Controlling contacts and contours using preformed ceramic inserts. AB - Current adhesive techniques and materials that seal both enamel and dentin have revolutionized modern restorative dentistry. Unfortunately, the durability problems associated with direct polymeric materials of the past have not been adequately solved. Nevertheless, when cost and esthetics form part of the treatment decision process, patients presenting with Class 2 defects are most often provided with a direct restorative option. Direct composite resin restorations are fraught with problems largely related to the mechanical stresses that accompany polymerization shrinkage. A partial solution is to incorporate prefabricated ceramic inserts into the substance of the composite resin, thereby decreasing the volume of directly cured restorative material and effectively reducing the magnitude of the polymerization stresses. SONICSYS approx is a unique addition to the restorative continuum that takes the insert strategy one step further by using specifically shaped sonically driven diamond-coated preparation tips to adjust the cavity form to fit presized ceramic proximal inlays. The SONICSYS approx system represents a technique intermediate between a direct resin composite and a laboratory fabricated inlay. This article describes the background of this development, and the components and application of the system. In addition, within the presentation of a case study, operative innovations are introduced that improve interfacial integrity and allow for the conveyance of predictable contacts and proper physiological contour. PMID- 11199696 TI - Use low-tech ideas to streamline your dental office. PMID- 11199697 TI - Regarding rationale for using single-use disposable air/water syringe tips, Raghunath Puttaiah, BDS, MPH; James A. Cottone, DMD; John Guildersleeve, DDS; et al (November 1999, p. 1056). PMID- 11199698 TI - Gloves--continuing effectiveness, new technologies, and recommendations. PMID- 11199699 TI - Dynamics of dental implants and orthodontics in today's periodontal prosthesis. AB - Periodontal prosthesis refers to multidisciplinary efforts to stop disease progression, correct deformities created by dental diseases, and establish a therapeutic occlusion to restore the form and function of the masticatory system. These efforts are critical for the long-term prognosis and maintenance of the guarded teeth and the overall prosthesis. This article presents a functionally and esthetically challenging case, which illustrates a multidisciplinary approach -specifically implantology and orthodontics--and how they impact on each other during treatment. The role and importance of dental implants and orthodontics in setting up a case is illustrated in this article. PMID- 11199700 TI - The role of enamel matrix proteins in periodontal regeneration. PMID- 11199701 TI - Prognosis vs outcome: predicting tooth survival. AB - The assignment of prognosis is one of the most important functions undertaken in clinical practice, yet there is little evidence to support the current decision making process. This article will review four articles that evaluate the traditional method of assigning a prognosis and predicting tooth survival. Limitations of the current method of assigning a prognosis are discussed, and models are presented that should allow clinicians to be more confident in their projections. PMID- 11199702 TI - All-ceramic restorations--predicting esthetic restorative success. PMID- 11199703 TI - Efficacy of a chlorine dioxide-containing mouthrinse in oral malodor. AB - Studies have suggested that when chlorine dioxide is contained in a mouthrinse, it neutralizes volatile sulfur compounds in mouth air. The efficacy of a chlorine dioxide-containing mouthrinse in the reduction of oral malodor was evaluated in a randomized, controlled, double-blind, parallel group study of 31 men and women. Subjects with a maximum odor pleasantness score of < or = -1 (slightly unpleasant/stale) on a 7-point ordinal scale at both screening and baseline were randomized to treatment with the chlorine dioxide-containing rinse (n = 16) or distilled water (negative control) (n = 15). Oral malodor was evaluated at baseline (prerinse) and at 2, 4, 8, 24, 48, 72, and 96 hours postrinse by both a trained, previously calibrated panel of organoleptic judges and a factory calibrated portable sulfide monitor. The sulfide monitor measured concentrations of volatile sulfur compounds in the subjects' mouth air 3 minutes after completion of the organoleptic assessment at each time point. The correlation between the organoleptic assessments and log-transformed sulfide monitor values was evaluated. With the chlorine dioxide mouthrinse, a statistically significant improvement in odor pleasantness, reduction in odor intensity, and reduction in oral volatile sulfur compound concentrations compared to the water control were evident at 2 hours postrinse and persisted through 8 hours postrinse. The mean (+/- SD) odor pleasantness improved from -1.25 +/- 0.31 at baseline to -0.73 +/- 0.33 at 2 hours postrinse in the chlorine dioxide group compared to -1.40 +/- 0.38 at baseline to -1.31 +/- 0.67 at 2 hours in the control group (P < 0.01). Odor pleasantness reached its maximum change from baseline to 0.63 +/- 0.45 at 8 hours postrinse. The mean (+/- SD) log-transformed sulfide monitor measurement decreased from 5.40 +/- 0.29 at baseline to 5.17 +/- 0.13 at 2 hours postrinse in the chlorine dioxide group, but increased from 5.47 +/- 0.40 at baseline to 5.56 +/- 0.54 at 2 hours in the control group (P < 0.01). As measured by the sulfide monitor, the mean volatile sulfur compound concentration in the chlorine dioxide group reached its minimum level at 8 hours postrinse (change from baseline in the log-transformed Halimeter measurement of -0.35 +/- 0.31). Thus, this study demonstrates that a one-time use of a chlorine dioxide-containing mouthrinse significantly improves mouth odor pleasantness, reduces mouth odor intensity, and reduces volatile sulfur compound concentrations in mouth air for at least 8 hours after use. PMID- 11199704 TI - Effect of alendronate on immature human dental root explants. AB - This study investigated the use of alendronate in the formation of new dentin in vitro. Extracted human premolar and molar teeth with immature apices were grown in tissue culture medium for 60 days. Six control specimens were grown without alendronate in the medium, and 22 experimental specimens were grown with alendronate at [10(-9) M] in the medium. Newly formed dentin was stained with tetracycline and procion brilliant red at days 1 to 3, 30 to 33, and 60. Specimens were decalcified and 5-micron sections were prepared for examination using fluorescent microscopy. New dentin formation was measured in microns at the most apical region, at 125-micron from the apical measurement and at 250-micron from the apical measurement. The alendronate group had 57.15% more growth than the control group at the most apical region, and this difference was significant (p = 0.0001). The results indicate that alendronate at [10(-9) M] is effective in accelerating dentin formation in vitro. PMID- 11199705 TI - Temperature rise during Er:YAG and Nd:YAP laser ablation of dentin. AB - This in vitro study compared temperature rises during cavity preparation with an Er:YAG laser, Nd:YAP laser, and a high-speed handpiece. Eighteen teeth were sectioned longitudinally and divided into six groups: group 1 was treated with a carbide bur on a high-speed dental handpiece; group 2 was treated with an Er:YAG laser with an energy of 140 mJ, a pulse repetition rate of 4 Hz; and group 3 was treated with an Nd:YAP laser with an energy of 240 mJ, a pulse repetition rate of 10 Hz. In these groups no water cooling was used. Groups 4 to 6 were treated in the same way, but with water spray. Temperature increases were measured at different dentin thicknesses by a microthermocouple attached to the inner side of the pulp chamber. Water cooling was essential to reduce temperature effects in all groups. Nd:YAP laser induced significantly higher temperature rises than Er:YAG or handpiece. Temperature response to the Er:YAG laser and the handpiece seemed to be similar. PMID- 11199706 TI - Effect of gutta-percha solvents on surface microhardness of IRM fillings. AB - Eighty identical samples of IRM were prepared and embedded in acrylic resin. The samples were polished, rinsed, and divided into experimental groups and controls, 10 specimens each. Each experimental group was treated for 1 or 5 min with one of the following gutta-percha solvents: chloroform, xylene, or halothane. Sterile saline was used as a control. Treatment consisted of pipetting each solvent onto the external IRM surface. The specimens were then sealed in plastic assay tubes for the corresponding exposure periods. At each time period, surface microhardness of the samples was measured using a mini-load hardness tester with a 500 g load for 20 s. It was found that xylene and halothane caused significant reduction in surface microhardness of IRM after 5 min (p < 0.01). Chloroform caused significant reduction in surface microhardness of IRM after 1 min of treatment (p < 0.01). Chloroform caused total dissolution after 5 min of treatment. Saline caused only minor and nonsignificant changes in surface microhardness of IRM. PMID- 11199707 TI - Radiation dose reduction during endodontic therapy: a new technique combining an apex locator (Root ZX) and a digital imaging system (RadioVisioGraphy). AB - This study was undertaken on 14 teeth in order to evaluate a new technique for radiation dose reduction during endodontic therapy. After examination of the preoperative film, usually available in the patient file, an apex locator (Root ZX) was used to measure the working length. Complete chemomechanical debridement was then performed, and the master cone was evaluated by a digital imaging system (RadioVisioGraphy (RVG)). Obturation was performed when measurements of the electronic device and RVG were comparable. A postoperative image was made by the RVG system to evaluate the final obturation. A clinical and radiographic follow up examination (follow-up period: 6 to 8 months) revealed satisfactory apical healing. These results indicated that a successful obturation technique can be performed by a single radiation exposure, using the RVG unit for master cone evaluation. This technique may be useful in medically compromised patients who need not to be exposed to excessive or repeated radiation during endodontic therapy. PMID- 11199708 TI - Apical microleakage of radiolabeled lysozyme over time in three techniques of root canal obturation. AB - The three methods of obturation assessed in this study were lateral condensation (80 teeth), Thermafil (40 teeth), and McSpadden (40 teeth). All teeth were prepared to the master apical file 30 and widened coronally by Gates Glidden burs before being randomly assigned to experimental groups to be filled by each technique; they were then sealed with nail polish, except for the apical 1 mm. Quantitative evaluation of apical microleakage for each technique was obtained after periods of 1 day, 7 days, 14 days, and 28 days of immersion in a lysozyme solution labeled with radioactive iodine by preparing horizontal sections of the teeth and measuring the level of radioactivity in each section using a gamma counter. Initial (1-day) leakage was least in the Thermafil group and was significantly different from the other techniques. Leakage was greatest in the laterally condensed samples. By the end of the study (28th day) values for lateral condensation were lowest, but were significantly different only for the McSpadden group. For all techniques leakage was most significant in the first 3 mm from the apex and was very low below this level so that all methods can be considered as giving a hermetic seal below 3 mm. PMID- 11199709 TI - Effects of a bacterial cell wall fragment on monocyte inflammatory function. AB - Gram-negative bacteria recovered from necrotic pulps of teeth with periapical lesions have been shown to promote bone resorption through the effects of their lipopolysaccharide (LPS). Recently, it was shown that microflora of root-filled teeth with persisting periapical lesions consisted mainly of single species of Gram-positive bacteria. But Gram-positive bacteria do not contain LPS and their role in the development of periapical lesions is not clearly understood. The purpose of this study was to evaluate the effects of muramyl dipeptide (MDP), a cell wall component of both Gram-negative and Gram-positive bacteria, on cytokine release from monocytes. Human monocyte cultures were treated with MDP or LPS and interleukin-1 beta, and tumor necrosis factor-alpha levels in the supernatants were estimated. MDP and LPS stimulated cytokine release, but the effect of MDP was significantly less than that of LPS. PMID- 11199710 TI - Torque during canal instrumentation using rotary nickel-titanium files. AB - Nickel-titanium engine-driven rotary instruments are used increasingly in endodontic practice. One frequently mentioned problem is fracture of an instrument in the root canal. Very few studies have been conducted on torsional characteristics of these instruments, and none has been done under dynamic conditions. The purposes of this study were to measure the torque generated and the apical force applied during instrumentation with a commercial engine-driven nickel-titanium file system, and to relate torque generated during simulated clinical use to torsional failure of the instruments. Ten extracted human teeth (five with small-sized and five with medium-sized straight root canals) were instrumented with Quantec Series 2000 files, and the torque and apical force generated were measured. The applied apical force was generally low, not exceeding 150 g in either small or medium canals. The torque depended on the tip size and taper of each instrument, and on canal size. Instruments with 0.05 and 0.06 taper generated the highest torque, which was greater in small than in medium canals. The torque at failure was significantly (p < 0.001) higher than torque during instrumentation, but with considerable variation in the extent of the difference. PMID- 11199711 TI - Defects in rotary nickel-titanium files after clinical use. AB - The purpose of this study was to analyze the type and frequency of defects in nickel-titanium rotary endodontic files after routine clinical use, and to draw conclusions regarding the reasons for failure. All of the files (total: 378, Quantec Series 2000) discarded after normal use from a specialist endodontic practice over 6 months were analyzed. Almost 50% of the files showed some visible defect; 21% were fractured and 28% showed other defects without fracture. Fractured files could be divided into two groups according to the characteristics of the defects observed. Torsional fracture occurred in 55.7% of all fractured files, whereas flexural fatigue occurred in 44.3%. The results indicated that torsional failure, which may be caused by using too much apical force during instrumentation, occurred more frequently than flexural fatigue, which may result from use in curved canals. PMID- 11199712 TI - CD45/isotypes expression in the immune cells of human periapical lesions. AB - Expression of some leukocyte antigens (including CD45) and its isoforms (CD2, CD4, CD5, CD6, CD7, and CD8) was examined in the human periapical granulation tissue samples in the present study. The majority of the infiltrating cells expressed heavy molecular-weight isoforms of the CD45 antigen. Expression of CD2, CD5, CD6, and CD7 antigens was also detected, implying significant roles for these antigens in the immune reaction taking place in periapical lesions. This suggests that the immune response taking place at the periapical region is predominantly cellular and the humoral responses to antigenic challenge are conducted mainly by regional lymph nodes. PMID- 11199713 TI - Sulfated glycosaminoglycan synthesis and its regulation by transforming growth factor-beta in rat clonal dental pulp cells. AB - Dental pulps contain sulfated glycosaminoglycans (GAGs), such as chondroitin 4 sulfate (CSA/4CS), dermatan sulfate (CSB/DS), and chondroitin 6-sulfate (CSC/6CS). Sulfated GAGs play important roles in mineralization and collagen fibrillogenesis during primary, secondary, and reparative dentin formations. Transforming growth factor-beta (TGF-beta) is a potent regulator for several extracellular matrix (ECM) components and modulates the proliferation and differentiation. Using rat clonal dental pulp cells (RPC-C2A), we investigated the constituents of GAGs synthesized by the cells and the effect of TGF-beta on their synthesis by measuring the radioactivity of [35S]sulfate incorporated into GAG fractions. Cellulose acetate electrophoresis analysis revealed that RPC-C2A cells synthesized CSA and CSB but not CSC and that 10 ng/ml of TGF-beta increased the production of CSA and CSB in the cell/ECM fraction. Measurement of [35S]sulfate incorporation showed a significant increase in the amount of GAGs by TGF-beta, 1.3-fold CSA, and 1.2-fold CSB in the cell/ECM fraction. In the medium fraction the most secreted GAG was CSA, whereas CSB was stored in the cell/ECM fraction. Secreted CSA in the medium was markedly increased by 10 ng/ml of TGF beta (1.7-fold). These findings indicate that CSA and CSB are major sulfated GAGs synthesized by RPC-C2A cells and that TGF-beta acts as a stimulator of sulfated GAG synthesis in dental pulp cells. PMID- 11199714 TI - A simple method for the analysis of root canal preparation. AB - The purpose of this article is to present a simple and easy method for in vitro analysis of root canal instrumentation that permits one to observe and measure the diameter of a root before and after instrumentation, using the teeth themselves as control. PMID- 11199715 TI - Pulpal pain diagnosis--a review. AB - Evidence gathered from our studies and the work of others appears to support the presence of two distinct nerve pain pathways in the dental pulp, represented by fast conducting A-delta and slow conducting C-fibers. Each of these types of fibers has different pain characteristics: A-delta fibers evoke a rapid, sharp, lancinating pain reaction, and C-fibers cause a slow, dull, crawling pain. Pain response thresholds vary in different regions of the tooth, and thermal, osmotic, ionic, and electric stimuli involve different mechanisms to provoke nerve excitation of the dental pulp. Evidence also points to the fact that the incidence of pain increases as the histopathosis worsens. On interrogation, patients who manifest severe or referred pain almost always give a previous history of pain in the tooth with the ache. Eighty percent of patients who give a previous history of pain manifest histopathologic evidence of chronic partial pulpitis with partial necrosis, the untreatable category, for which endodontics or extraction is indicated. The other 20% exhibit histopathosis of the pulp with slight inflammation to chronic partial pulpitis without necrosis, a treatable category. Clinically, one can determine the degree of pulp histopathosis by asking the patient about a previous history of pain in the involved tooth. This history of previous pain adds another dimension in diagnosis for the clinician as to whether the painful pulpitis is reversible. This information also aids in referred pain localization. PMID- 11199716 TI - A suspected periradicular scar: treat or not? AB - This paper presents an unusual case of a tooth with multiple adjacent endodontic problems. The diagnosis was complicated by a bony scar that untypically was located around the apex of one of the teeth. PMID- 11199717 TI - Allergic reaction after rubber dam placement. AB - In the last few years allergic reactions to natural rubber latex (NRL) have increased in dental practice affecting both the dental team and patients. Some case reports discuss the potential risks of hypersensitivity to NRL products. An adverse patient reaction after dental rubber dam placement is reported. About 1 min after the isolation of the tooth with a rubber dam the patient presented signs and symptoms of hypersensitivity. Oxygen and intravenous hydrocortisone were administered and the patient kept under observation. After 2 h she had stable vital signs and no more allergics symptoms. It is unclear whether components of the NRL dam or the cornstarch powder incorporated with the rubber dam was responsible for the allergic reaction. Dentists must be aware of the health problem and be prepared for an adequate management in dental practice. PMID- 11199718 TI - Effect of 10% carbamide peroxide bleaching gel on enamel microhardness, microstructure, and mineral content. AB - The effect of 10% carbamide peroxide on human enamel subsurface layers was examined. Microhardness, microstructure, and mineral content were studied in such a manner that control and test side were located on the same tooth. Longitudinally sectioned samples were obtained from six teeth and Vickers microhardness of the enamel was measured. Enamel microstructure was analyzed using a scanning electron microscope and subjected to electron probe microanalysis for chemical analysis of calcium (Ca) and phosphorus (P). The concentration of Ca in the bleaching gel was measured spectrophotometrically and the concentration of P was measured photometrically. Results showed that a bleaching gel of 10% carbamide peroxide did not significantly affect the microhardness of the enamel. Scanning electron microscopic analysis showed local changes in enamel microstructure similar to those of initial caries. Electron probe microanalysis showed lowered concentrations of Ca and P; in addition the Ca:P ratio was lowered. There was some Ca and P in the bleaching gel after use. It is concluded that 10% carbamide peroxide causes local microstructural and chemical changes in enamel that are likely not clinically significant. PMID- 11199719 TI - In vitro yeast infection of human dentin. AB - An in vitro model was developed for investigation of Candida albicans penetration into human dentinal tubules. The model consisted of a dentin disc mounted between two cuvettes that each had a circular opening facing the disc. The cuvettes were filled with Tryptic-Soy-Broth, and the pulpal side cuvette was inoculated with C. albicans and incubated at 37 degrees C in air until growth occurred in the uninoculated cuvette or up to 30 days. The system was also used with Enterococcus faecalis. Completely glue-covered dentin specimens served as negative controls. Brown & Brenn-stained histological preparations of the specimens were examined with light microscopy. The time needed before growth occurred in the uninoculated cuvette showed great variation with C. albicans, whereas E. faecalis penetrated within 1 to 5 days of incubation. Slight penetration both by hyphae and yeast cells was observed in specimens inoculated with C. albicans, whereas specimens inoculated with E. faecalis showed deep and effective penetration. This study demonstrates the penetration of dentin as a possible pathway of infection by C. albicans. However, dentin penetration by C. albicans was slow and limited in comparison with E. faecalis. PMID- 11199720 TI - Leakage along apical root fillings in curved root canals. Part I: effects of apical transportation on seal of root fillings. AB - Occurrence of apical transportation (AT) may complicate the root filling procedure and result in a compromised seal. In part I of this study, human mandibular premolars with single, curved (21 to 39 degrees), or straight canals were prepared by Lightspeed or a step-back hand filing technique. An AT index was determined using a double exposure radiographic technique. The prepared canals were obturated using lateral condensation of gutta-percha. Leakage along the apical 3 mm of root filling was measured with a fluid transport model. After hand filing, AT and perforation occurred in 87% of the curved canals. The AT indices were > or = 0.4 mm. After Lightspeed preparation, AT occurred in only 19% of the curved canals. The hand filing/curved group leaked statistically significantly more than the hand filing/straight and Lightspeed/curved groups (p = 0.002). We conclude that occurrence of AT is a factor that negatively influences the apical seal when curved canals are obturated by lateral condensation of gutta-percha. PMID- 11199721 TI - Whole genomic DNA probe for detection of Porphyromonas endodontalis. AB - The purpose of the present study was to develop a DNA probe for Porphyromonas endodontalis. Pure cultures of P. endodontalis were grown in TYP medium, in an anaerobic chamber. DNA was extracted from the P. endodontalis and labeled using the Genius System by Boehringer Mannheim. The labeled P. endodontalis DNA was used in dot-blot hybridization reactions with homologous (P. endodontalis) and unrelated bacterial samples. To determine specificity, strains of 40 other oral bacterial species (e.g. Porphyromonas gingivalis, Porphyromonas asaccharolytica, and Prevotella intermedia) were spotted and reacted with the P. endodontalis DNA probe. None of the panel of 40 oral bacteria hybridized with the P. endodontalis probe, whereas the blot of the homologous organism showed a strong positive reaction. To determine the sensitivity of the probe, dilutions of a P. endodontalis suspension of known concentration were blotted onto a nylon membrane and reacted with the probe. The results of our investigation indicate that the DNA probe that we have prepared specifically detects only P. endodontalis and can detect at least 3 x 10(4) cells. PMID- 11199722 TI - Antibiotic susceptibility of bacteria detected from the root canal exudate of persistent apical periodontitis. AB - Intracanal exudates in persistent endodontic cases were sampled for detecting bacteria using a preculture method, and the antibiotic susceptibility of the bacteria identified was examined. Twelve species were recovered from 15 cases. The species most commonly detected were alpha-Streptococcus and Enterococcus. The results of the antibiotic susceptibility tests revealed that Enterococcus was highly resistant to antibiotics tested, especially to cephalosporin products. Enterococcus is known as one of the bacteria that show multidrug resistance. In cases of prolonged endodontic treatment, a specific antibiotic prescription would play an important role for efficient treatment. Collecting data about antibiotic susceptibility could be helpful. Identification, however, take approximately 2 wk and a further study to develop the method that rapidly informs us about the antibiotic susceptibility that might be needed. PMID- 11199723 TI - bcl-2, p53, and MIB-1 in human adult dental pulp. AB - Little is known about the renewal of some groups of cells in dental pulp, and the occurrence and significance of physiological cell death in dental pulp is not yet understood. The possibility of odontoblast disappearance by apoptosis has been proposed, and the presence of apoptotic cells in the rat and human odontoblastic and subodontoblastic layers has been recently described. bcl-2 and p53 are proteins involved in the apoptotic pathway, whereas MIB-1 is a proliferating cell marker. The aim of our study was an immunohistochemical evaluation of bcl-2, p53, and MIB-1 in healthy normal pulps of young human subjects. With bcl-2 immunostaining, some positive cells were found in the odontoblastic and subodontoblastic layers, whereas with MIB-1, only a few stromal cells were positive, and all odontoblasts were consistently negative. No cells were positive to p53. The bcl-2 immunoreactivity of the cells of the odontoblastic and subodontoblastic layers could help to explain the presence of apoptotic cells found in these regions. PMID- 11199724 TI - An in vitro study of the cytotoxicity of two root canal sealers. AB - The purpose of this in vitro study was to determine the cytotoxicity of two root canal sealing materials (AH26 and AH-Plus). This cytotoxicity test (agar diffusion test) was conducted based on the procedures described in the International Organization for Standardization. The biological reactivity of a mammalian monolayer, L929 mouse fibroblast cells, in response to the tested agents was determined. After the 48-h observation period, the cell cultures exposed to the test articles discs for AH26 and AH-Plus exhibited severe reactivity (grade 4). The positive control article exhibited moderate reactivity (grade 3). No signs of reactivity (grade 0) were noted for the negative control article or the negative control discs. The tested samples of AH26 and AH-Plus are considered cytotoxic and do not meet the requirement of the agar diffusion test. Similar cytotoxicity results have been found in the literature for AH26 and other root canal sealing cements. PMID- 11199725 TI - Dentin bonding and sealing ability of a new root canal resin sealer. AB - The aims of this study were to find a dentin bonding system suitable for root canal treatment using a newly developed root canal resin sealer, and to examine its sealing ability. The sealer was composed of vinylidene fluoride/hexafluoropropylene copolymer, methyl methacrylate, zirconia, and tributylborane catalyst. The effects of dentin conditioners and primers on dentin bonding were studied by tensile bond strength testing and scanning electron microscopy. Apical and coronal leakage were evaluated at 1-, 4-, and 12-wk intervals by a dye penetration test using a methylene blue solution. Pulp Canal Sealer EWT and Sealapex were used as controls. Significantly high bond strength was obtained by treating dentin with EDTA, followed by application of a glutaraldehyde/2-hydroxyethyl methacrylate primer. The experimental resin sealer produced a significantly superior coronal seal at 12 wk when compared with the two control sealers (p < 0.05). Scanning electron microscopic examination revealed few gaps at the resin sealer-dentin interface. PMID- 11199726 TI - In vitro study of the penetration of Streptococcus sanguis and Prevotella intermedia strains into human dentinal tubules. AB - The persistent presence of bacteria in the root canal system often leads to the failure of treatment. The purpose of this study was to determine in vitro penetration of Streptococcus sanguis and Prevotella intermedia into dentinal tubules. Samples obtained from human teeth were inoculated with a strain of S. sanguis (NCTC 7853) and P. intermedia (NCTC 93336) for 20 days. Bacterial penetration into tubules was investigated at scanning electron microscopy and light microscopic level. The results showed that S. sanguis could penetrate into dentinal tubules 382.3 microns, whereas P. intermedia could penetrate 25.9 microns. It was observed that P. intermedia had not penetrated into all dentinal tubules. If penetration occurred the depth was quite limited. PMID- 11199727 TI - Retreatment decisions--a comparison between general practitioners and endodontic postgraduates. AB - One of the most subjective areas with regard to interexaminer variations is the dental radiograph. The variations in radiographic interpretation lead to differences in treatment planning decisions. This study compared the endodontic retreatment planning decisions for endodontically treated teeth between 12 general practitioners and 12 endodontic postgraduate students. Utilizing dental radiographs of completed cases, both groups were asked to make treatment choices based on two hypothetical ages of a case: 1 or 3 yr postoperatively. General practitioners chose to initiate treatment at an earlier date and also chose more extensive treatment modalities. The age of the root filling was looked on as more important in treatment planning by the endodontics postgraduates. PMID- 11199728 TI - Persistent pain related to root canal filling and apical fenestration: a case report. AB - Endodontic treatments may give rise to persistent pain whose origin is sometimes difficult to determine. Although it is unusual, pain may occur due to apical fenestrations following endodontic treatment. If this occurs, the solution is surgical intervention. This surgical procedure consists of raising a flap to expose the fenestration, followed by curettage of any overextended canal filling materials that may be potentially irritating to the underlying mucosa, remodeling of the apex, and its repositioning below the level of the cortical bone. A case is described that illustrates this clinical situation. The case also demonstrates information that can be obtained from tomodensitometric films. PMID- 11199729 TI - Apexification of an infected untreated immature tooth. AB - A case of a traumatized permanent young tooth in which apexification occurred without the benefit of endodontic treatment is reported. It illustrates how a immature incisor that underwent pulp necrosis and periapical inflammation could progress to complete apical formation. PMID- 11199730 TI - An unusual indication for root resection. AB - This report presents an unusual indication for root resection of a lower molar tooth and also reviews the history of root resection. PMID- 11199731 TI - Pulpal responses to cooling tooth temperatures. AB - This investigation measured pulpal blood flow and sensitivity to electrical stimulation as tooth temperatures were lowered. Dark rubber dams were placed on test teeth before placement of the cooling device in an attempt to shield gingival microcirculation. Laser Doppler flowmetry was used to measure pulp blood flow, whereas sensory thresholds were recorded simultaneously using an electric pulp tester. As tooth temperatures were lowered, the teeth became less responsive. Pulp blood flow also slowed, but did not completely stop. Results indicated that sensory thresholds were altered, and in some subjects, abolished, without total cessation of pulpal blood flow. PMID- 11199732 TI - Comparative evaluation of antibacterial effects of Nd:YAG laser irradiation in root canals and dentinal tubules. AB - The antibacterial effects of the Nd:YAG laser on contaminated root canals and dentinal tubules were observed as the aim of this study. The samples were inoculated with Streptococcus sanguis (NCTC 7853) and Prevotella intermedia (NCTC 93336), and the effects of Nd:YAG laser were tested on these teeth. The specimens were lased with 1.8 W and 2.4 W Nd:YAG laser for 30 s, and the presence of bacteria in tubules was observed under light microscopy. The 1.8 W laser sterilized the tubules in 86.3% of sections inoculated with S. sanguis, whereas 2.4 W laser sterilized in 98.5% of the sections. Both laser powers sterilized all samples inoculated with P. intermedia. The scanning electron microscopic observations supported the light microscopic findings. PMID- 11199733 TI - Histopathological evaluation of the dental pulps in crown-fractured teeth. AB - Trauma is a common cause of pulpal damage. In traumatic injuries, the first priority is to protect the vitality of pulps. But the time between the trauma and treatment must be short to preserve vital, noninflamed pulps. The aim of this study was to investigate the histopathological changes in pulpal tissues at different time periods after crown fractures. Twenty-three teeth with enamel and dentin fractures, with and without pulp exposure were evaluated. The reasons for seeking dental treatment were aesthetic consideration, pain, or discomfort. The extirpated pulps were histologically prepared for microscopical evaluation. There was myelin degeneration surrounding the axons and edema in the early posttraumatic stages (17 h). In the later stages (4 to 20 days), the tissues showed varying degrees of inflammation, and neuronal degeneration such as intramyelin edema, aberrant myelin synthesis, and axonal swelling. PMID- 11199734 TI - Antimicrobial activity and flow rate of newer and established root canal sealers. AB - Endodontic sealers that possess both optimum flow ability and antimicrobial properties may theoretically assist in the elimination of microorganisms located in confined areas of the root canal system. The antimicrobial effects and the flow rate of the following sealers were investigated and compared: Kerr Pulp Canal Sealer EWT, Grossman's Sealer, ThermaSeal, Sealer 26, AH Plus, and Sealer Plus. The agar diffusion test was used to assess the antimicrobial activity of the sealers. In the flow assay, the sealers were placed between two glass slabs and a weight of 500 g was placed on the top of the glass. The diameters of the formed discs were recorded. All root canal sealers tested showed some antimicrobial activity against most of the microorganisms. There were no significant differences between the materials tested (p > 0.05). All root canal sealers also flowed under the conditions of this study. Statistical analysis of the results revealed that AH Plus and Kerr Pulp Canal Sealer EWT had flow values significantly superior to the other sealers tested (p > 0.05). Taken together, these findings suggest that these sealers have the potential to help in the microbial control in the root canal system. PMID- 11199735 TI - Comparative analysis of curved root canal preparation using nickel-titanium instruments with or without EDTA. AB - The purpose of this study was to examine the effect of the use of EDTA as a root canal irrigant in curved root canals instrumented with nickel-titanium (Ni-Ti) instruments. Twenty extracted maxillary molars were selected. Mesiobuccal roots were used. Teeth were mounted in self-curing acrylic resin bases to allow standardized angulation of the initial and final radiographs. The preinstrumentation radiographs were made with a #15 file in the canal. The canals were instrumented with Ni-Ti instruments by the step-back technique, using or not using EDTA. The post-instrumentation radiographs were made with a #30 file in the canal. The films were projected (x10 magnification), drawn, and superimposed. Ni Ti instruments used with EDTA were less effective in maintaining the original path of curved canals. PMID- 11199736 TI - Quality of root-end preparations using ultrasonic and rotary instrumentation in cadavers. AB - Prior investigations have demonstrated dentinal cracking and chipping during ultrasonic preparation of the root-end. This study compared the frequency of cracking and chipping in two groups, cadaver and extracted teeth, using an indirect resin technique. Preparations were performed using either a 33 1/2 inverted cone bur in a high-speed handpiece, or with ultrasonics using a CT-2 tip at either high or low intensity. After replication of the root-end in epoxy resin, all teeth were evaluated for cracking and chipping under scanning electron microscopy. Statistical analysis using a general contingency table or ANOVA with Scheffe post-hoc analysis (p = 0.05) revealed no significant difference between all groups in terms of root-end cracking. In extracted teeth (n = 15), rotary instrumentation produced less chipping than either ultrasonic technique. Varying the intensity was not significant. There was no significant difference between any instrumentation group in cadaver teeth (n = 10) related to the amount of chipping. PMID- 11199737 TI - Influence of albumin and collagen on the cell mortality evoked by zinc oxide eugenol in vitro. AB - Zinc oxide-eugenol (ZOE) is cytotoxic in vitro but does not cause pulp damage. Various dentin proteins may play a protective role in vivo. We investigated the influence of bovine serum albumin (BSA) and collagen on ZOE cytotoxicity in the Millipore filter test and a dentin barrier test. Agar or agarose with 1% or 5% BSA or calf collagen (1% and 2%) were introduced between L-929 fibroblasts and test specimens. ZOE was severely toxic in the absence of BSA. However BSA (1% and 3%) reduced cell damage to 50% and 35%. In contrast, collagen did not provide protection from ZOE cytotoxicity. When dentin was loaded with 3% BSA and the "pulpal" side of a dentin barrier test chamber was perfused with cell culture medium containing 3% BSA, cytotoxicity of ZOE was completely inhibited. Therefore we conclude that albumin may be one factor responsible for the absence of ZOE toxicity in pulp studies. PMID- 11199738 TI - Cytotoxicity of mineral trioxide aggregate using human periodontal ligament fibroblasts. AB - The purpose of the present study was to compare the cytotoxicity of mineral trioxide aggregate (MTA) to other commonly used retrofilling materials, Super-EBA and amalgam. This was accomplished using a cell viability assay for mitochondrial dehydrogenase activity in human periodontal ligament fibroblasts after 24-hr exposure to extracts of varying concentrations of the test materials, in both freshly mixed and 24-hr set states. Methyl methacrylate 2% (vol/vol) served as the positive control, and complete culture medium served as the negative control. Differences in mean cell viability values were assessed by ANOVA (p < 0.05). In the freshly mixed state, the sequence of toxicity was amalgam > Super-EBA > MTA. In the 24-hr set state the sequence of toxicity at a low extract concentration was Super-EBA > MTA, amalgam, and Super-EBA > amalgam > MTA at a higher extract concentration. This study supports the use of MTA in the root-end environment. PMID- 11199739 TI - Effect of canal drying methods on the apical seal. AB - The purpose of this study was to observe the seal obtained in human root canals under different in vitro treatment conditions. Root canals of freshly extracted human maxillary incisors received traditional biomechanical preparation and irrigation with 10% NaClO, followed by a final rinse of distilled water. Teeth were divided into four groups. In group 1, each root canal was dried with one paper point. In group 2, each root canal was dried with four paper points. Group 3 was dried with four paper points, followed by a gentle burst of warm air. Group 4 was dried using four paper points, followed by an internal 200 degrees C heat probe. Twenty canals in each group were filled with a gutta-percha cone and a zinc oxide-eugenol sealer, whereas 20 were filled with a glass ionomer sealer. All teeth were immediately immersed in India ink for 1 or 4 wk. The teeth were cleared, and the dye penetration-leakage measured with an accuracy of +/- 0.01 mm. Optimum sealing conditions were observed when the canal was dried with paper points and a 200 degrees C probe. There were no significant differences between 1 and 4 wk immersion. Glass ionomer sealer appeared more susceptible to the wet condition of the root canal walls than zinc oxide-eugenol sealer. An additional 40 teeth were prepared in the same manner as the dye penetration tests to observe the drying conditions of the root canal walls, and the moisture inside the canals was measured to an accuracy of 0.0001 g. The highest degree of internal canal wall dryness was found in group 4. PMID- 11199740 TI - The radicular groove: its potential clinical significance. AB - This report examines three clinical cases of root-filled teeth with primary endodontic lesions. During endodontic surgery, an area of incomplete root bifurcation beginning in the coronal or middle third of the root surface and terminating at or near the apical foramen were observed. The radicular grooves of two teeth were eliminated using a round bur ("saucerization"), and the resulting defect was filled with a bone substitute or calcium sulfate and covered by an absorbable collagen membrane. The other tooth was extracted, the groove was eliminated with a similar technique, and the tooth was replanted. Bacteria have been reported in chronic apical lesions. Our observations suggest that after conventional endodontic therapy, the etiology of a nonresolving primary endodontic lesion may be bacteria of endodontic origin sequestered within the protective confines of an apical-radicular groove. PMID- 11199741 TI - Idiopathic root resorption: report of a case. AB - A case of multiple idiopathic apical root resorption in a 26-yr-old female patient is presented. A review of the literature revealed that extensive idiopathic root resorption is unusual. Neither local nor systemic etiological factors were found in our case. Examination of parents and siblings did not reveal a familiar tendency. Radiographs and clinical evaluation showed a very poor prognosis for most of the teeth present in the mouth of our patient. PMID- 11199742 TI - Custom-fabricated endodontic implants: report of two cases. AB - Teeth that have lost a good portion of alveolar support can be stabilized and maintained by the use of endodontic endosseous implants. Two hopeless cases were restored to function with ceramic-coated, custom-fabricated chrome-cobalt implants. The technique for fabrication is described. PMID- 11199743 TI - Five canals in a mandibular second premolar. AB - A case of conservative endodontic therapy for a mandibular second premolar with five root canals is described. A thorough knowledge of the root canal anatomy, careful interpretation of the radiographs, and access cavity modifications are essentials for enhancing intracanal procedures. PMID- 11199744 TI - Antimicrobial substantivity of chlorhexidine-treated bovine root dentin. AB - Previous studies have demonstrated antimicrobial substantivity in root canal dentin up to 7 days after treatment with chlorhexidine. This in vitro study assessed the antimicrobial substantivity of chlorhexidine-treated bovine root dentin over a period of 21 days. Sixty standardized bovine root sections were randomly divided into three equal groups, and their canals immersed in one of the following solutions: (i) sterile saline; (ii) 2.5% NaOCl; or (iii) 0.2% chlorhexidine (CHX). Half the specimens in each group were treated with the solution for 5 min and the other half for 7 days. After solutions were removed, the specimens were incubated at 37 degrees C in Brain Heart Infusion broth containing Enterococcus faecalis (ATCC 29212). A fresh inoculum was added to the broth every other day over a 21-day period. The canals were then enlarged with sterile burs, and the dentin shavings collected and cultured for the presence of cultivable bacteria in the dentinal tubules. Specimens treated with CHX for 7 days demonstrated significantly less dentin colonization by E. faecalis than the other specimens. CHX has potential as an intracanal medicament, if it can be applied for a period of at least 7 days. PMID- 11199745 TI - Effect of smear layer and direction of dentinal tubules on osteoblast adhesion to human dentin tissue. AB - The purpose of this study was to investigate the effect of smear layer and direction of dentinal tubules on osteoblast adhesion to human dentin tissue in vitro. Dentin disks were made from human premolars extracted for orthodontic reasons. Dentin disks were cut either perpendicularly to the long axis of the tooth or at 45 degrees to the long axis of tooth. The smear layer was removed by 34% phosphoric acid gel from half of the dentin disk surface. Human osteoblast like Saos-2 cells were grown in RPMI medium with 10% fetal bovine serum and 1% antibiotic/antimycotic cocktail under standard cell culture conditions. Cells were seeded into Nunc four-well culture plates at 1.5 x 10(5) cells per well with dentin disks in the bottom of each well. After 1 day in culture the dentin disks along with cells grown on their surface were examined with a scanning electron microscopy. Osteoblasts attached and spread on the dentin surface and formed a monolayer in the presence and absence of a smear layer. Cells spread over the dentinal tubules despite their direction. These results suggest that cell adhesion and spreading of osteoblasts is not influenced either by the existence of a smear layer or the direction of the dentinal tubules on the dentin surface. PMID- 11199746 TI - The mutagenic potential of AH+ and AH26 by Salmonella/microsome assay. AB - The aim of this study was to examine the mutagenic potential of canal sealers AH+ and AH26 by Salmonella/microsome assay. The materials were tested immediately after mixing, 1 hr and 1 month later, respectively. The dimethyl sulfoxide extracts of sealers in amounts of 3.0, 1.5, and 0.75 microliters/plate were used. The plated bacterial strains of Salmonella were TA 98 and TA 100. The results showed that AH+ is mutagenic toward strain TA 100 1 hr after mixing. One month after mixing, mutagenic activity was expressed only in TA 98. Paste A showed strong mutagenicity toward TA 100. AH26 was more mutagenic to the TA 100 immediately after mixing, 1 hr later, and 1 month after it was polymerized. Also it was mutagenic toward TA 98 in the polymerized condition. Further examinations should be conducted to establish a definitive conclusion about mutagenic potential for these two endodontic materials. PMID- 11199747 TI - Effect of systemic doxycycline on alveolar bone loss after periradicular surgery. AB - Studies in the periodontic literature have shown an average of 0.5 mm to > 1.0 mm of bone loss after full thickness flap reflection. Similar literature has revealed that the tetracycline family of antibiotics can prevent bone loss. The purpose of this study was to observe the effect of systemic Doxycycline on crestal alveolar bone loss after periradicular surgery in beagle dogs. Five beagle dogs were used in two phases of this study. In the first phase (control sides), after reflecting full thickness flaps in one mandibular quadrant, notches were placed in the enamel of the third and fourth premolar teeth using a one quarter round bur. Using magnification, measurements were taken from the reference notches to the height of the alveolar crest. After 8 wk, flaps were reflected in the same quadrant and measurements retaken, and the amount of bone loss was then measured. In the second phase (experimental sides), the same procedure was performed on the contralateral mandibular quadrant, but the dogs were placed on 4.4 mg/kg/day of Doxycycline for 10 days after reflections of full thickness flaps. After another 8 wk, the area was reflapped and measured. There was significantly (p < 0.01) less bone loss on the Doxycycline-treated side. PMID- 11199748 TI - Evaluation of cell culture cytotoxicity of five root canal sealers. AB - The cytotoxicity of four calcium hydroxide-based root canal sealers (Sealapex, CRCS, Apexit, and Sealer 26) and one zinc oxide-eugenol-based sealer (Fill Canal) was evaluated microscopically for morphological changes in rat peritoneal macrophages. The least cytotoxic sealer was Fill Canal, followed in increasing order of cytotoxicity by CRCS, Sealer 26, Apexit, and Sealapex. PMID- 11199749 TI - Chemomechanical reduction of the bacterial population in the root canal after instrumentation and irrigation with 1%, 2.5%, and 5.25% sodium hypochlorite. AB - Given the importance of bacteria in the development of periradicular lesions, the eradication of the root canal infection is paramount in endodontic treatment. This study evaluated the in vitro intracanal bacterial reduction produced by instrumentation and irrigation with 1%, 2.5%, and 5.25% sodium hypochlorite (NaOCl) or saline solution. Root canals inoculated with Enterococcus faecalis were instrumented and irrigated with the solutions tested. Canals were sampled before and after preparation. After serial dilution, samples were plated onto Mitis salivarius agar, and the colony-forming units grown were counted. Inhibitory effects of the three NaOCl solutions on E. faecalis were also evaluated by means of the agar diffusion test. All test solutions significantly reduced the number of bacterial cells in the root canal (p < 0.05). There was no significant difference between the three NaOCl solutions tested (p > 0.05). Nonetheless, all NaOCl solutions were significantly more effective than saline solution in reducing the number of bacterial cells within the root canal (p < 0.05). The three NaOCl concentrations showed large zones of inhibition against E. faecalis. The results of this study suggest that regular exchange and the use of large amounts of irrigant should maintain the antibacterial effectiveness of the NaOCl solution, compensating for the effects of concentration. PMID- 11199750 TI - Immunolocalization of macrophages and transforming growth factor-beta 1 in induced rat periapical lesions. AB - Apical periodontitis was induced in Wistar rats by exposing the pulp chamber of right mandibular first molars to the oral environment. Animals were killed 0, 5, 10, 15, 20, 30, 60, and 80 days after lesion induction. Microradiographic and automated image analysis showed that the lesions expanded significantly in a time dependent manner from day 0 to day 20 (0.039 mm2/day, p < 0.05, active phase) and stabilized thereafter (chronic phase). A linear regression test revealed a positive correlation between the numbers of ED-1 positive macrophage per microscopic high power field and the periapical lesion size during the active phase (r = 0.98, p < 0.01). Immunohistochemical studies showed that transforming growth factor-beta 1 positive macrophages distributed around the root apex and areas showing bone resorption during active lesion phase, whereas TGF-beta 1 positive osteoblasts were detected during the chronic stage (days 30, 60, and 80 after pulp exposure). Histologically TGF-beta 1 positive osteoblasts possessed a large, round nucleus as well as an abundant cytoplasm and located in close vicinity to areas exhibiting reparative bone formation. These results suggest that macrophages may play important role(s) in the initiation and development of periapical lesions and TGF-beta 1 may play dual roles in both bone resorption and deposition in induced rat periapical lesions. PMID- 11199751 TI - Effect of root canal sealers and irrigation agents on retention of preformed posts luted with a resin cement. AB - This study examined the effect of three sealers and four irrigants on retention of Dentatus preformed posts luted with Panavia 21 resin cement. Gutta-percha with one of the following sealers--EWT, AH26, Nogenol, or no sealer (control)--was used to fill the root canals of 160 autoclaved incisor and premolar tooth roots. After 72 hr 8 mm post spaces were created with Dentatus Probos Pathfinders and Dentatus reamers. After irrigating the post spaces with saline, 5.25% NaOCl, 50% citric acid followed by NaOCl, or 40% H3PO4, followed by NaOCl, Panavia 21 TC cement was introduced into the canal on the Dentatus #4 stainless steel post's threads. An up-and-down and counterclockwise motion and then a forward twist seated the posts without engaging dentin. Mesiodistal and faciolingual radiographs visualized the chambers. After 72 hr posts were removed axially with an Instron at 5 mm/min. Surprisingly, using Nogenol sealer reduced post retention whereas EWT and AH26 increased retention compared with no sealer. Post retention improved after acid etchants, especially for AH26. PMID- 11199752 TI - Macroscopic and microscopic analysis of the palato-gingival groove. AB - With the objective of correlating the anatomical aspects of the palato-gingival groove with its etiology, diagnosis, and alternative treatments, 13 permanent maxillary incisors with palato-gingival grooves were selected from a large sample and subjected to macroscopic and microscopic analysis of groove morphology. The palato-gingival groove occurred most frequently on the lingual aspect of the lateral incisor (11 of 13), and its coronal and radicular extensions were on the disto-lingual surface of the incisors (7 of 13 and 6 of 13, respectively). Deformation of the contour of the pulp cavity was noted subjacent to the groove (9 of 13), along with diminished enamel and dentin thickness (11 of 13 and 13 of 13, respectively) and an increase in cement (12 of 13). The groove was observed extending to the apical third in nine specimens, and a direct communication between the pulp and periodontium was observed in only one case. From these examinations it is concluded that the palato-gingival groove can be clinically diagnosed, preventing subsequent problems; however microscopic analysis of the affected tooth is necessary to allow precise evaluation of the groove's extension and damage to the dental structure. PMID- 11199753 TI - Smear layer influence on the apical seal of four different obturation techniques. AB - The purpose of this study was the in vitro evaluation of four techniques for the obturation of the root canal system in the presence or absence of a smear layer. Ninety-six human upper central incisors were instrumented using the pressureless crown-down technique and irrigated with 5.25% NaOCl. The teeth that had the smear layer removed were irrigated with this solution in combination with 17% EDTA. The teeth were obturated with lateral condensation with an accessory or standardized cone as the main cone, with vertical condensation of warm gutta-percha or with thermoplasticized injectable gutta-percha. Apical leakage was assessed by measuring the linear penetration of methylene blue dye with a stereomicroscope. The results showed no significant differences in the degree of leakage with and without the smear layer when the samples were considered as a whole. However, when the groups were assessed separately, teeth in the lateral condensation with an accessory main cone group and teeth in the thermoplasticized group leaked less with a smear layer present. In contrast teeth with lateral condensation and a standardized main cone leaked more with a smear layer present. In the vertical condensation groups there was no difference attributable to the smear layer. PMID- 11199754 TI - Efficacy of final irrigation--a scanning electron microscopic evaluation. AB - The purpose of this in vitro study was to determine the degree of removal of pulpal remnants and smear layer from root canals after final irrigation with three different solutions. During instrumentation the step-back preparation and 1% NaOCl were used. The final 4-min, 30-ml irrigation varied as follows: group I, 10 ml of 1% NaOCl + 10 ml of 10% citric acid + 10 ml of distilled water; group II, 15 ml of 0.5% NaOCl + 15 ml of EDTA-T; and group III, 10 ml of 5% NaOCl + 10 ml of 3% H2O2 + 10 ml of 5% NaOCl. Scanning electron microscopic photomicrographs were evaluated for the mean number of visible open dentinal tubules by three observers. The largest number of visible tubules in the three groups was in the cervical third, followed by the middle and apical thirds. There was no statistically significant difference between groups I and II when third was compared with third; however, groups I and II had significantly more visible dentinal tubules than group III. PMID- 11199755 TI - Furcation groove of buccal root of maxillary first premolars--a morphometric study. AB - Furcation grooves on the palatal aspect of the buccal roots of 35 maxillary first premolars, randomly selected, were assessed and found to exist in 97% of the sample. The buccal roots were sectioned into slices, 1 mm thick, and morphometric horizontal and vertical measurements were taken by a Toolmaker Microscope. The slice with the deepest invaginations served as the reference plane. The deepest invaginations were found to be at a mean distance of 1.18 mm from the bifurcation, with a mean depth of 0.4 mm. The canal had a kidney-shaped appearance in cross-section, and the mean distance from the invagination to the canal wall was 0.81 mm. It is thus hazardous to use rotary instruments for flaring these roots and any circular-shaped post space preparation at this level is contraindicated. The outcome of such procedures might be root thinning, perforation, or vertical root fracture, thus causing a poor prognosis. PMID- 11199756 TI - Effect of using electronic apex locators on selected endodontic treatment parameters. AB - The purpose of this study was to determine the effect of using electronic apex locators on the number of radiographs taken and the adequacy in length of the final obturation. Patients in an undergraduate student endodontics clinic participated in the study. The working length (WL) was estimated by the authors for all cases (36 teeth; 58 canals), using both a preoperative standardized radiograph and an electronic measurement. The students were then asked to place WL files to one of the estimates (electronic or radiographic; chosen by random assignment) and take a WL radiograph. Neither the students nor their instructors knew which method was chosen for the estimates. Once treatment was completed, the total number of working radiographs was counted. The number of cases with acceptable (0 to 2 mm short of the apex) or unacceptable obturation was also blindly registered. An electronic estimate of the WL improved length quality of the final obturation, compared with a radiographic estimate. The number of working radiographs taken was less in the electronic apex locator group in anterior and premolar teeth, but not in molars. PMID- 11199757 TI - Broken instrument removal--two cases. AB - This paper reports two clinical aids for the removal of broken instruments in root canals using a combination of hand instrumentation and ultrasonic devices. This technique is based on two phases: hand instrumentation with stainless-steel K-file instruments for bypassing the fragments, and K-files mounted on an ultrasonic handpiece for loosening and retrieval of the broken instruments. This method offers the following advantages: conservation of the remaining dentin wall of the root canal and elimination of the necessity for surgical treatment. PMID- 11199758 TI - Central giant cell granuloma: a troublesome lesion. AB - This case reports a central giant cell granuloma, an uncommon but potentially troublesome idiopathic benign lesion. Its radiographic similarity to a routine inflammatory periradicular lesion led to not only delay in diagnosis, but also further delay in successful treatment. PMID- 11199759 TI - Nasal fistula associated with dental infection: a report of a case. AB - Most clinicians have come across a patient with difficult symptoms to diagnose. Often confusion occurs between odontogenic and nonodontogenic causes of sinus discomfort. On many occasions, sinus pain is due to purely dental causes, whereas in other situations dental pain is reported when the sinuses are infected. Due to the intimate association between the roots of the maxillary teeth and the floor of the nasal cavity and maxillary sinuses, diagnosis may be difficult. The following is a case report of a nasal fistula that developed from an abscessed maxillary central incisor. PMID- 11199760 TI - Gutta-percha softening: "Hemo-De" as a xylene substitute. AB - The putative hazardous nature of chloroform and xylene implies that safer substitutes should be considered. Standard cylindrical gutta-percha samples were immersed in Hemo-De, a xylene substitute, for 60 s at 37 degrees C. Weight loss of a sample, after drying, was used as a measure of its solubility. Master and accessory cone gutta-percha of three brands were compared. The highest solubility of all kinds of gutta-percha was in chloroform, which served as a positive control. The average solubility of all samples in xylene and Hemo-De was 61% and 52% of that in chloroform, respectively. DMS gutta-percha was more soluble than of Hygienic and DeTrey. Master cone gutta-percha of all brands was more soluble than that of their accessory cones. These results indicate that (a) large differences exist in the solubility of gutta-percha and (b) Hemo-De dissolved gutta-percha in a range similar to that of xylene and may be considered as a potential substitute for this organic solvent. PMID- 11199761 TI - Evaluation of pH and calcium ion release of three root canal sealers. AB - The pH and calcium ion release of three root canal sealers--Sealapex, Sealer 26, and Apexit--were assessed at 24 and 48 hr, and at 7 and 30 days after spatulation. After manipulation, the sealers were placed in 1-cm-long tubes measuring 4 mm in diameter and immersed in a glass flask containing 10 ml of deionized water, which was hermetically sealed and stored at 37 degrees C. The tubes were removed at the scheduled times and the water in which they were immersed was tested for pH with a pHmeter and for released calcium by atomic absorption spectrophotometry. Starting 48 hr after immersion, Selapex produced an alklaine pH and released significantly higher calcium amounts compared with the other two sealers, with even more pronounced results after 30 days. On the basis of the results obtained, we conclude that Sealapex presented the highest calcium and hydroxyl release, especially after longer time intervals, whereas Sealer 26 showed highest release during the initial periods (i.e. during its setting time). Apexit presented the least satisfactory results. PMID- 11199762 TI - In vitro evaluation of antimicrobial activity of sealers and pastes used in endodontics. AB - The antimicrobial activity of four root canal sealers (AH Plus, Sealapex, Ketac Endo, and Fill Canal), two calcium hydroxide pastes (Calen and Calasept), and a zinc oxide paste was evaluated. Seven bacterial strains were used, six of them standard; Micrococcus luteus ATCC 9341, Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 25922, and Enterococcus faecalis ATCC 10541. There was a wild strain of Streptococcus mutans isolated from saliva obtained in an adult dental clinic. Activity was evaluated using the agar diffusion method with Brain Heart Infusion agar and Muller Hinton medium seeded by pour plate. Calcium hydroxide-based sealers and pastes were either placed directly into 4.0 x 4.0 mm wells or by using absorbent paper points. The plates were kept at room temperature for 2 hr for diffusion. After incubation at 37 degrees C for 24 hr, the medium was optimized with 0.05 g% TTC gel and inhibition haloes were measured. All bacterial strains were inhibited by all materials using the well method. However, when the materials were applied with absorbent paper points, Enterococcus faecalis was not inhibited by zinc oxide, and Pseudomonas aeruginosa was not inhibited by AH Plus, Fill Canal, and the zinc oxide-based paste. We conclude that sealers and pastes presented antimicrobial activity in vitro and culture medium optimization with 0.05 g% TTC gel facilitated observation of the inhibition haloes. PMID- 11199763 TI - Cytotoxicity evaluation of perforation repair materials on human periodontal ligament cells in vitro. AB - Perforation of a tooth structure resulting in communication of the pulp space with periodontium occasionally occurs during endodontic therapy. For the best prognosis, the perforation area must be sealed as soon as possible. Because these materials will be in direct contact with periodontal tissues, their cytotoxic potential must be evaluated before clinical use. The purpose of this study was to determine the cytocompatibility of three perforation repair materials (amalgam, resin, and glass ionomer). Cultured human periodontal ligament (PDL) cells were used to evaluate the cellular response resulting from these materials by cell viability and proliferation assays. Twenty-seven 5 x 4 mm cylinders of each material were fabricated for this study. All tested materials were cytotoxic to human PDL cells. Both types of material and time affected cell viability and proliferation. Resin exhibited the most cytotoxic effects followed by glass ionomer and amalgam during a 14-day incubation period. Amalgam and glass ionomer slightly inhibited cell viability and growth in the first 24 hr, compared with the control. Amalgam or glass ionomer may initially react more favorably to PDL cells than resin. The present model of cultured human PDL cells is simple, relatively cheap, and easily established and propagated under standardized conditions in any laboratory. Furthermore, this method allows long-term observation of human cellular reactions and thus might be a preliminary screening test for initial biocompatibility of dental materials. PMID- 11199764 TI - Growth inhibitory activity of gutta-percha points containing root canal medications on common endodontic bacterial pathogens as determined by an optimized quantitative in vitro assay. AB - Gutta-percha points containing calcium hydroxide, zinc oxide (ZnO), a mixture of ZnO and chlorhexidine (ZnO/CHX), iodine-polyvinylpyrrolidone (ZnO/J-PVP), or a mixture of CHX and J-PVP and ZnO (ZnO/CHX/J-PVP) were tested for their ability to inhibit growth of pure cultures of bacterial species commonly involved in endodontic infections (Peptostreptococcus micros, Streptococcus intermedius, Enterococcus faecalis, and Porphyromonas gingivalis). To quantitate growth inhibition, an in vitro assay was established that controlled for important parameters of root canal infection. Approximately 10(7) bacteria per assay were suspended in diluted human serum and co-incubated with the gutta-percha points in an anaerobic atmosphere for up to 2 wk. Aliquots used for determination of colony counts were taken on days 0, 1, 2, 4, 7, and 14 of incubation. As judged by colony-forming unit reduction kinetics and final counts, calcium hydroxide had better growth inhibitory activity than ZnO/CHX, ZnO/J-PVP, and ZnO alone for all bacteria tested except Peptostreptococcus micros. The combination of CHX and J PVP with ZnO did not render results different from those of ZnO/CHX or ZnO/J-PVP. The results of this study support the introduction of standardized assays for testing antibacterial properties of root canal medications under conditions that more closely resemble those encountered in endodontal infections. PMID- 11199765 TI - Adhesion of human osteoblasts on root-end filling materials. AB - Adhesion of human osteoblasts to root-end filling materials (mineral trioxide aggregate (MTA), IRM, composite, and amalgam) was observed by scanning electron microscopy. Root-end filling materials were inserted into 96-well flat-bottomed plates and condensed to disks of approximately 1 mm thick and the same diameter as the wells. After the disks were set, they were placed in the bottom of Nunc four-well culture plates at one disk per well. Then human osteoblasts were seeded into the wells at 1.5 x 10(5) cells per well. After 1 day in culture the disks of root-end filling materials along with cells grown on their surface were examined with a scanning electron microscopy. Results showed that osteoblasts attached and spread on MTA and composite by forming a monolayer. Osteoblasts also attached on amalgam, but with few cells spreading. In the presence of IRM, osteoblasts appeared rounded with no spreading. These results indicate that osteoblasts have a favorable response to MTA and composite resin compared with IRM and amalgam. PMID- 11199766 TI - Effect of a fifth-generation bonding agent on vascular responses in rats. AB - In the last years, several single-bottle dental adhesives have been developed. They are supposed to chemically adhere to dentin, and a liner to protect pulp is not thought to be necessary. In the case of direct pulp capping, hemorrhage control is an important step in success, but little is known about the effect of these new bonding agents on pulpal bleeding. The aim of this study was to evaluate the effect of a new one-step single-bottle adhesive on the smooth muscle contraction of rat uterine muscle and carotid arteries. Efficacy of the bonding agent was compared with that of epinephrine (control), and the contraction forces induced were recorded using a force displacement transducer. Statistical analysis of data revealed that the bonding material produced epinephrine-like concentration-dependent contractions of the smooth muscle, suggesting that one step bonding agents may act as candidates for hemorrhage control without the use of an additional agent in direct pulp capping procedures. PMID- 11199767 TI - Anaerobic bacterial extracts influence production of matrix metalloproteinases and their inhibitors by human dental pulp cells. AB - The role of human dental pulp (HDP) cells in extracellular matrix degradation in pulpitis is still unclear. In this study, the effects of sonicated bacterial extracts (SBEs) from Prevotella intermedia, Fusobacterium nucleatum, Porphyromonas endodontalis, and Porphyromonas gingivalis on the balance between the production of matrix metalloproteinases (MMPs) and that of their inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] by HDP cells were examined. HDP cells were treated with SBEs, and their culture media were later harvested. MMP activities and TIMP concentrations were determined by use of independent measurement strategies and sensitive ELISAs. The production of MMP-1 and MMP-2 was accelerated by all SBE. On the other hand, TIMP-1 production was slightly elevated; and TIMP-2 production was markedly inhibited by all of the extracts. SBEs derived from these anaerobic bacteria seemed to affect the acceleration of extracellular matrix degradation activity by HDP cells. These findings suggest that HDP cells stimulated by bacterial byproducts may be involved in the pathogenesis of pulpitis. PMID- 11199768 TI - Impact of two theoretical cross-sections on torsional and bending stresses of nickel-titanium root canal instrument models. AB - The use of nickel-titanium in the manufacture of endodontic instruments has given rise to continuous-rotation canal preparation techniques. These techniques involve unidirectional torque, meaning that files are under constant stress and strain when operating. The study presented herein compares torsional and bending stresses in triple U and triple helix models. This was done by applying the boundary integral method to theoretical cylindrical models. The two theoretical models underwent very different torsional stresses, both in terms of intensity and distribution. Bending stresses were much more similar, but to obtain the same curvature, bending moments had to be different. The results of the mathematical calculations indicated that triple U and triple helix instruments should be used for different operating procedures. PMID- 11199769 TI - Scanning electron microscopic investigation of the surface of gutta-percha cones after cutting. AB - The surface of auxiliary gutta-percha cones after cutting with different methods was evaluated. The tips of gutta-percha cones size fine were cut off using scissors, a razor blade against a glass slab, a razor blade combined with a calibrator, or a razor blade/calibrator followed by a further cutting with a razor blade against a glass slab. Samples were examined under scanning electron microscopy. Cutting with scissors and razor blade/calibrator produced significant irregularities in the cone surface. Cutting with razor blades against a glass slab, with or without previous use of a calibrator, allowed the development of a smooth gutta-percha cone surface. PMID- 11199771 TI - The use of two pluggers for the obturation of an uncommon C-shaped canal. AB - The complex configuration of C-shaped canals in mandibular second molars make root canal treatment unusually difficult. The present case highlights their unpredictable canal anatomy and describes the use of two pluggers simultaneously to downpack the main canals. The effect of such a modification on the high-flow characteristics of thermosoftened gutta-percha in vertical condensation is discussed. PMID- 11199772 TI - A successful nonsurgical treatment of an endodontic failure. AB - This study presents a relatively uncomplicated endodontic failure that responded to nonsurgical treatment. Speculation as to other interpretations of the failure with related treatment plans is offered to highlight how significant diagnosis can be in determining outcomes. PMID- 11199773 TI - The effect of immediate vs. delayed post space preparation on the apical seal of a root canal filling: a study in an increased-sensitivity pressure-driven system. AB - A 5 mm remaining length of root canal filling, after post space preparation, is commonly assumed to maintain sealing ability similar to that of the intact filling. Post spaces were prepared either immediately using hot pluggers, or later, using drills. The sealing ability of the fillings, 5 mm remaining length, were compared with each other and with an intact root canal filling control, using radioactive tracer in a pressure-driven system. When no pressure was applied, no differences could be detected between either of the groups and the control. When a pressure of 120 mm Hg was applied to the same teeth, the control group clearly maintained a better seal than each of the experimental groups, which did not significantly differ from each other. These results suggest that (a) the pressure-driven system was more sensitive than the passive leakage assay that failed to detect differences even at 14 days; (b) a remaining root canal filling of 5 mm was inferior to the intact root canal filling; and (c) the immediate post space preparation with hot pluggers did not differ from a delayed preparation with drills. PMID- 11199774 TI - Cytotoxic and nongenotoxic effects of phenolic compounds in human pulp cell cultures. AB - Phenolic compounds are widely used in clinical dentistry as sedatives for the dental pulp, as disinfectants for caries, and as root canal medications. The pathobiological effects of various phenolic compounds on human dental pulp fibroblasts were investigated with Hoechst 33258 fluorescence assay and DNA precipitation assay. All phenolic compounds showed cytotoxicity in Hoechst 33258 fluorescence assay by inhibiting cellular DNA in a concentration-dependent manner. The 50% inhibition concentrations required to decrease the cellular DNA contents by guaiacol, phenol, eugenol, and thymol were 9.8, 4.5, 0.9, and 0.5 mM, respectively. However these phenolic compounds did not cause DNA single-strand breaks in cultured human pulp fibroblasts. These results indicate that phenolic compounds are cytotoxic agents but are without genotoxic effects on human pulp fibroblasts in vitro. However care should be taken to reduce the possibility of pulpal as well as periapical irritations from inadvertent extrusion of these substances in clinical usage. PMID- 11199775 TI - Retrograde seal in ultrasonically prepared canals. AB - The sealing ability of various retrofilling materials was compared. The root canals of 85 single-rooted teeth were cleansed and obturated with gutta-percha without sealer using lateral condensation. The apical 3 mm of the roots were resected and divided into positive control, negative control, and five experimental groups. The experimental teeth received root-end cavity preparation to 3 mm depth using an ultrasonic retroprep tip. The retrocavities were dried and divided into five groups to receive the following materials: amalgam with varnish, amalgam with Clearfil Liner Bond II, thermoplasticized gutta-percha (TGP) with sealer, Ketac-fil, and Super-EBA. After immersion in India ink for 7 days, the roots were demineralized, cleared, and evaluated for dye leakage under a stereomicroscope. Statistical analysis showed that Super-EBA, Ketac-fil, and TGP with sealer demonstrated less leakage than amalgam with varnish and amalgam with Clearfil Liner Bond II (p < 0.05). Super-EBA also leaked significantly less than Ketac-fil or TGP sealer (p < 0.05). No significant difference was found between Ketac-fil and TGP or between the two groups filled with amalgam (p > 0.05). PMID- 11199776 TI - The essential endodontic literature: a survey of postgraduate program directors. AB - Hundreds of new articles are added to the body of knowledge in endodontics each year. However, a comparatively small number of articles have had a disproportionately large influence on the progress and development of the specialty of endodontics. A survey of postgraduate program directors was conducted to attempt to identify a highly selective short list of articles that program directors felt should be included on every postgraduate reading list. The survey results were then compared with the more objective benchmark of citation indexing. The results of this survey suggest that the collective opinion of the postgraduate program directors correlates well with the results obtained from citation analysis. PMID- 11199777 TI - A comparison of the morphological changes after Nd-YAG and CO2 laser irradiation of dentin surfaces. AB - The purpose of this study was to compare the morphological changes after Nd-YAG and CO2 laser irradiation on dentin surfaces with or without the smear layer. Eighty-one 3-mm-thick dentin specimens collected from the middle third of molar crowns were used. The dentin surfaces were ground to #320, #400, and #600 grit in series to create a smear layer. Half of the specimens were treated with 14% EDTA for 2 min to remove the smear layers. The lasers were applied on each specimen perpendicularly with 1-mm focus distance to the dentin surface for 4 s. The parameters for the Nd-YAG laser were 50 mJ, 100 mJ, and 150 mJ at 10 pps, 20 pps, and 30 pps, and for the CO2 laser were 2 W, 3 W, and 4 W at 5 ms x 20 pps, 10 ms x 10 pps, 20 ms x 20 pps, 50 ms x 2 pps, 100 ms x 2 pps, and 200 ms x 2 pps. The results showed that the Nd-YAG laser caused crater and melting of the dentin surface, especially in dentin specimens with smear layers. The CO2 laser produced extensive cracking lines on dentin surfaces with a smear layer, whereas surface erosion and crater formation were found on specimens without a smear layer. In conclusion, both the laser types and smear layer have a significant influence on the morphological changes of dentin surfaces irradiated by lasers. PMID- 11199778 TI - Canal enlargement by Er:YAG laser using a cone-shaped irradiation tip. AB - To solve the problem of mechanical instrumentation, we developed a cone-shaped laser irradiation tip. This tip delivers 80% of the energy of the laser laterally and 20% of the energy forward. The tip was equipped with a water nozzle. The aim of this study was to examine the effect of Er:YAG laser irradiation using this tip on root canal enlargement and debridement. As a root canal model, a hole (0.5 x 5 mm) was drilled into a bovine dentin block. The tip was inserted into this hole and moved from the apex to the orifice (45 mm/min). The power of 10 mJ x 10 pps caused enlargement of the canal dimension by 106.5%. 20 and 40 mJ x 10 pps caused enlargements of 116.3 and 118.6%. 30 mJ x 10 pps caused the biggest change (129.8%). Scanning electron microscopic observations indicated that the dentin surface after laser preparation appeared cleaner than that obtained after preparation by drilling. This technique may have the advantage of decreasing the preparation time. PMID- 11199779 TI - Smear layer removal by EGTA. AB - The purpose of this study was to compare the effects of ethylene glycol-bis (beta aminoethyl ether)-N,N,N', N'-tetraacetic acid (EGTA) and EDTA on removal of the smear layer by using scanning electron microscopy. Fifteen single-rooted teeth were instrumented to size 60. Three teeth served as the control group, and the remaining teeth were assigned into two groups. After instrumentation, root canals of the first group were irrigated with 10 ml of 17% EDTA, and the second group was irrigated with 10 ml of 17% EGTA for 2 min. Both were then irrigated with 10 ml of 5% NaOCl. The teeth in the control group were irrigated with only 10 ml of 5% NaOCl. Then the specimens were sectioned longitudinally and processed for scanning electron microscopy. The results showed that the smear layer was completely removed by EDTA, but it caused erosion of the tubuli. EGTA was somewhat effective in removing the smear layer without inducing erosion. Our results suggest that EGTA is an alternative chelator for removing the smear layer. PMID- 11199780 TI - In vitro cytotoxicity of a new epoxy resin root canal sealer. AB - The cytotoxic effects of a new epoxy resin-based root canal sealer (AH-plus), together with those of two other commonly used endodontic sealers (AH26 and zinc oxide-eugenol), have been studied in vitro on a culture of human gingival fibroblasts. Cytotoxicity was assessed by direct incubation of sealers' extracts with the cultured fibroblasts at different time intervals. Morphological and cytotoxic effects of the sealers were evaluated microscopically and spectrophotometrically using the neutral red cytotoxicity assay. Our results demonstrated that the cytotoxic effects induced by zinc oxide-eugenol were detectable as early as 1 hr after mixing and remained at a high level until completion of the experiment (5 wk). AH26, however, induced early cytotoxic effects that lasted for 1 wk, followed by a substantial reduction in cytotoxicity. Cytotoxicity of the AH-plus was confined to the early period of experiment and was no longer detectable after 4 hr of mixing. Comparison between the results obtained for each sealer revealed significant differences at particular time intervals. Our findings suggest the potential advantage of this sealer over the other two sealers. PMID- 11199781 TI - Sealing furcation perforations with silver glass ionomer cement: an in vitro evaluation. AB - Furcation perforations sealed with silver glass ionomer cement (Chelon Silver) were evaluated in vitro compared with amalgam. Access cavities were prepared in 25 extracted human molar teeth. The coronal orifices of the root canals were sealed with amalgam and varnish. Naturally occurring coronal leakage through the intact pulp chamber floor was determined quantitatively for each tooth, using a modified fluid transport model, under pressure of 1.2 Atm. Each tooth was then disconnected from the system, perforated at the furcation, and the perforation sealed with either Chelon Silver (10 teeth) or amalgam (10 teeth); five remaining teeth served as a negative control. After incubation for 24 h at 37 degrees C in 100% humidity, teeth were reconnected to the modified fluid transport system, and coronal leakage under pressure was evaluated at 1, 2, 6, 15, and 24 h. Leakage through each tooth was compared with that of its own intact pulp chamber floor before perforation and the groups compared with each other. No significant difference was found between the mean leakage of the intact pulp chamber floors of the two groups. Chelon Silver had a significantly better sealing ability than amalgam (p < 0.01): leakage rate of 0.007 and 0.017 microliter/min, respectively. It is concluded that Chelon Silver could be an adequate sealer for furcation perforations. PMID- 11199782 TI - Zebra. XIX. Part 2. Oral herpes zoster. PMID- 11199783 TI - Delayed replantation of avulsed mature teeth with calcium hydroxide treatment. AB - Three avulsed teeth that were replanted and splinted after approximately a 200 min dry extraoral period in two patients are presented. In case 1 calcium hydroxide treatment was performed 1 month after replantation, because the patient did not come for endodontic treatment on the day after replantation as requested. In case 2, calcium hydroxide treatment was initiated on the day after replantation. Calcium hydroxide treatment was used to prevent or treat inflammatory root resorption. During the follow-up periods the teeth reported in these cases have remained in a stable, functional position and did not reveal clinical ankylosis or replacement resorption. PMID- 11199784 TI - A case report of a compound odontoma causing delayed eruption of a central maxillary incisor: clinical and microscopic evaluation. AB - A case of a compound odontoma caused delayed eruption of a central incisor in the maxilla is presented with clinical, radiographic, and microscopic findings. The odontoma was surgically removed and microscopic examination showed a lot of crown like structures in a very irregular form, some of which were fused to each other at their apical parts. Enamel and pre-enamel were totally abnormal, whereas the inside of the pulp chamber tissue did not present any histological sign of functional tissue. The most homogeneous tissue was dentin. The removal of the odontoma was followed by a rapid eruption of the impacted central incisor. PMID- 11199785 TI - Long-term obturation quality using noninstrumentation technology. AB - The aim of the study was to evaluate and compare the sealing quality of hand- or vacuum-obturated root canals after hand instrumentation or noninstrumentation cleansing. A total of 60 single-rooted teeth were divided into six comparable groups. The root canals of three groups were instrumented with the balanced-force technique and obturated with gutta-percha condensation. The remaining teeth were cleansed and filled using noninstrumentation technology and the same sealers as with hand instrumentation (AH Plus, Apexit, Pulp canal sealer EWT). After aging the quality of coronal seal was assessed with a dye penetration method after perfusion with the dye under vacuum. The results of this study indicated superior sealing of the machine-filled roots (noninstrumentation technology), compared with laterally condensed conventionally filled root canals. PMID- 11199786 TI - Effects of calcium hydroxide and transforming [correction of tumor] growth factor beta on collagen synthesis in subcultures I and V of osteoblasts. AB - Collagen protein synthesis by osteoblasts is influenced by transforming growth factor-beta (TGF-beta 1) and is essential to bone formation. The effectiveness of TGF-beta 1 depends on efficient delivery of the growth factor to target cells, adequate binding to cell surface receptors, and an optimum environment for promotion of collagen synthesis. The effects of calcium hydroxide (Ca(OH)2), TGF beta 1, and Ca(OH)2/TGF-beta 1 co-administration on total protein, collagen protein, and noncollagen protein synthesis by early (subculture I) and late (subculture V) osteoblast cultures were tested. TGF-beta 1 significantly increased all protein synthesis in subculture I osteoblasts (p = 0.001; p < 0.001; p = 0.019). Ca(OH)2/TGF-beta 1 co-administration significantly increased total protein and collagen protein levels in subculture I osteoblasts as well (p = 0.048; p = 0.012). TGF-beta 1 increased total protein and collagen protein synthesis significantly in subculture V cells (p = 0.025; p = 0.01). These data indicate that co-administration of Ca(OH)2 and TGF-beta 1 enhances collagen synthesis by osteoblasts and may have implications for the clinical setting. PMID- 11199788 TI - Cementoenamel junction: microscopic analysis and external cervical resorption. AB - There is a lack of data regarding the shapes and distribution of the mineralized tissue that composes the cementoenamel junction. A sample of 198 permanent human teeth was analyzed by optical microscopy and scanning electron microscopy. Scanning electron microscopy showed three types of tissue interrelations: enamel overlapped by cementum; enamel and cementum edge-to-edge; and a gap, revealing a strip of exposed dentin. Using optical microscopy, a fourth type of cementoenamel junction was observed: cementum overlapped by enamel. The distribution of the hard tissues found at the cementoenamel junction is unpredictable and irregular both for any tooth type (e.g. on cuspids) and on any one individual tooth. Based on these results and on analysis of the mechanisms involved in cervical root resorption, it is possible to consider the cervical region as prone to external resorption. PMID- 11199787 TI - A comparison of the surface tension of calcium hydroxide mixed with different vehicles. AB - The aim of this study was to evaluate and compare the surface tension of different liquids that are used as potential agents to mix with calcium hydroxide in root canal treatment. We also tried to evaluate final surface tension values of the calcium hydroxide mixed with glycerin, Ringer's solution, anesthetic solution, and saline. Surface tension values were measured using a "Du Nouy" tensiometer. The results showed statistically significant differences between vehicles alone and the calcium hydroxide combinations and also indicated that anesthetic solution (p = 0.018, p < or = 0.02) is the most favorable vehicle with the lowest surface tension values. PMID- 11199789 TI - Lactate dehydrogenase leakage of hepatocytes with AH26 and AH Plus sealer treatments. AB - Numerous root canals filling materials are available in the field of dentistry, based on various formulas that contain a variety of different and partly mutagenic components, such as epoxy resin sealers, Ca(OH)2-based materials, and zinc oxide-eugenol cements. AH Plus root canal sealer will not release formaldehyde according to the manufacturer, although AH26 does. The purpose of this study was to analyze the leakage of lactate dehydrogenase (LDH) from rat hepatocytes after treatment with AH26 and AH Plus root canal sealers in vitro. Hepatocytes from male Sprague-Dawley rats were used to test the cytotoxicity of AH26 and AH Plus. The root canal sealers were mixed and then dissolved in the dimethyl sulfoxide to final concentrations of 0.01%, 0.04%, and 0.1% (wt/vol), with a dimethyl sulfoxide concentration of < 0.05%. Dosage-dependent and time dependent lactate dehydrogenase leakage values were measured and tested by one way ANOVA. The results showed that both AH26 and AH Plus are toxic to rat hepatocytes. At a low concentration, AH26 had a higher toxicity than AH Plus to rat hepatocytes. PMID- 11199790 TI - Biocompatibility of two current adhesive resins. AB - The purpose of the study was to evaluate the biocompatibility of two current adhesive resins and a calcium hydroxide cement. Fifty-four polyethylene tubes were filled with these dental materials, which were hand-mixed or light-cured according to the manufacturer's directions: group 1--Clearfill Liner Bond 2 (Kuraray); group 2--Single Bond (3 M); and group 3--calcium hydroxide cement (Dycal-Dentsply). The materials were implanted into dorsal connective tissue of rats, which were killed 7, 30, and 60 days after the implantation procedure. The implant sites were excised, immersed in buffered Karnovsky's fixative, and processed using routine histological techniques. Sections of 6 microns thickness were stained with hematoxylin and eosin and assessed under light microscopy. Both adhesive resins at 7 days elicited a moderate/intense inflammatory reaction that decreased over time. Fibrous capsules surrounding the tubes were observed at 30 days. Half of the samples in groups 1 and 2 showed thin fibrous capsule formation containing macrophages, capillaries, lymphocytes, fibroblasts, and collagen fibers. Connective tissue healing was observed even though many specimens exhibited a persistent inflammatory reaction mediated by macrophages and giant cells at the 60-day evaluation. Dycal allowed complete healing at 30 days with only a thin fibrous capsule. In conclusion, all experimental materials were successfully walled off by the connective tissue of the rat. However the adhesive resins may release particulates that may, in turn, induce a persistent local inflammatory reaction. Consequently, in this specific condition, these materials cannot be regarded as biocompatible. Dycal was less irritating than the adhesive resins and was better tolerated by the connective tissue. PMID- 11199791 TI - A method to assess rotary nickel-titanium files. AB - A number of studies have assessed the physical properties and durability of rotary nickel-titanium files. This study proposes a method that will permit this to be done in a controlled manner. Files of 0.04 taper; 25 mm in length; and in ISO sizes 25, 30, and 35 were each used four times in plastic blocks. The canal in the block had a working length of 17 mm; 30 degrees curvature; 15 mm radius of curvature; size 20 at the apex; and the curve began at 8 mm from the orifice of the canal. The irrigant used was Glyde. An electric handpiece was configured to rotate at 200 rpm and secured to the testing device, which also held the plastic block. The testing device controlled the depth of penetration at 17 mm; the load was at 8 N and the rate of penetration was at 120 mm/min. Controls were not subjected to use. Torsional moment (N-cm) and angular deflection (degrees) at failure were determined on a Torsiometer/Memocouple. Data (n = 5) were analyzed by analysis of variance. Tukey-Kramer intervals at the 0.05 significance level were determined. Torsional moment significantly increased with an increase in size. Torsional moment also significantly increased for used instruments, compared with controls. Angular deflection had a range of 480 degrees to 810 degrees for the instruments tested. PMID- 11199793 TI - Stress analysis of human tooth root using various root canal instruments. AB - This study compared external root stresses from instrumentation by several motor driven nickel-titanium instruments to stresses developed by hand files. Twelve curved first molar mesial roots were invested in PLM-9 photoelastic material to disclose net stress transmitted from the canal through the dentin. Minimal fringe patterns were observed during instrumentation with all techniques. Light-speed yielded the least change. In no case was a complete 60 psi fringe change noted. PMID- 11199792 TI - Effect of various mixing ratios on antibacterial properties and hardness of endodontic sealers. AB - Most chemically cured two-component dental materials, including endodontic sealers, are marketed with mixing instructions but with no strict mixing ratios. The present study evaluated the antibacterial properties and hardness of three endodontic sealers: Roth's cement (RC), CRCS, and AH26, mixed to four controlled consistencies within the range of the manufacturer recommendations. Using Enterococcus faecalis as the test microorganism, antibacterial activity was evaluated by agar diffusion and direct contact test. Surface hardness of sealers with the same consistency was evaluated on week-old specimens by the Knoop Hardness Number tester. In the agar diffusion test, light consistency of RC showed larger zones of inhibition than heavier consistency, whereas no significant differences were found with AH26 or CRCS. In the direct contact test, RC and CRCS exhibited complete inhibition of bacterial growth at all consistencies, whereas AH26 with the heavier consistencies did not inhibit bacterial growth at 24 h samples. The hardness of AH26 and CRCS was significantly lower with lighter consistencies. It is concluded that endodontic sealers possess different antibacterial and physical properties according to their mixing consistencies. PMID- 11199794 TI - Pulp capping of carious exposures: treatment outcome after 5 and 10 years: a retrospective study. AB - One hundred twenty-three pulp cappings had been performed by students in 1984 to 1987 (= 10-yr group) or in 1990 to 1992 (= 5-yr group) and were followed up in 1997. Teeth were checked for sensitivity (CO2/electrical pulp testing), percussion, and palpation; radiographs were taken to assess periapical status. In addition several other factors were determined that might have an influence on the success or failure rates, such as base material, type of restoration, site of exposure, etc. Results showed 44.5% failures (18.5% questionable and 37% successful cases) in the 5-yr group and 79.7% failing, 7.3% questionable, and 13% successful cases in the 10-yr group. As a factor of influence, the placement of a definitive restoration within the first 2 days after pulp exposure was found to contribute significantly to the survival rate of these teeth. PMID- 11199795 TI - Anaphylactic shock during endodontic treatment due to allergy to formaldehyde in a root canal sealant. AB - A 41-yr-old patient experienced an anaphylactic shock reaction caused by formaldehyde in a root canal sealant during endodontic treatment. The clinical events, positive skin tests, and a high level of immunoglobin E to formalin RAST (class 4) suggest the involvement of immunoglobin E-dependent mechanisms toward formaldehyde. This very infrequent observation in endodontic therapy focuses attention on the different pathological manifestations related to formalin, their mechanisms, and the prevention possibilities in dentistry. PMID- 11199796 TI - Orifice locating with a microscope. AB - The purpose of this study was to determine whether the use of the dental operating microscope (DOM) could increase the number of root canal orifices located in mandibular molars. Ninety-three first and 111 second extracted mandibular molars were used. With the naked eye, all access cavities were prepared and the number of canals in each root was recorded. Using a DOM with x8 x13 magnification, all teeth had the access cavity preparations again examined. With the naked eye, a total of 641 canals were seen in all teeth. After the DOM examination, 50 more canals could be visualized, representing a 7.8% increase in the total number of located canals. From these canals, 35 were located in the first molars and 15 in the second molars. The use of the DOM increases the number of root canal orifices located. PMID- 11199797 TI - Quality of apical seal in curved canals using three types of spreaders. AB - The aim of the present study was to evaluate the influence of spreader shape on the quality of obturation. Forty-five single canal teeth with varying degrees of apical curvature were used throughout. The canals were prepared using the step back technique and obturated with lateral condensation. The teeth were classified into three groups (A, B, and C) and treated as follows. Group A was treated with markedly conical, flat-ended spreaders (A to D; Dentsply-Maillefer, Ballaigues, Switzerland). Group B was treated with slightly conical (15 to 40) sharp-pointed CC-cord spreaders. Group C was treated with CC-cord, slightly conical but flat ended spreaders. The obturated teeth were decalcified in 7.5% nitric acid to obtain four cross-sections: the first at 2 mm from the apex and then the following three sections at 1-mm intervals. Section thickness was approximately 1 mm. Each section was photographed under a stereoscopic microscope. The following areas were measured on each of the microphotographs using a planimeter: (a) gutta percha mass, (b) mass of sealer, (c) foreign bodies, and (d) empty spaces. These four areas were added to determine total cross-sectional canal area and then the percent of that area attributable to a and to b + c + d was calculated. The statistical analysis of the data (parametric Student's t test for independent groups) revealed that only in group B was the area occupied by a, the gutta percha mass, significantly greater at all levels than the area occupied by b + c + d. Next in obturation effectiveness was group C, followed by group A. PMID- 11199798 TI - Surface tension of root canal irrigants. AB - The aim of this study was to evaluate the surface tension values of established and potential endodontic irrigants to which a surface active agent had not been added. Additionally, Cetredixine, a surfactant-containing 0.2% chlorhexidine gluconate solution, was included in the measurements. Surface tension measurements were performed using the ring method on a DuNouy tensiometer at a standard room temperature. Ringer's solution, saline solution, and distilled water had the highest surface tension values, whereas those of NaOCl (2.5% and 5%) and 17% EDTA were relatively low. Two anesthetic solutions, Ultracaine and Citanest, demonstrated values similar to NaOCl and EDTA, although a statistically significant difference was found between all solutions tested. Cetredixin displayed the lowest surface tension. A low surface tension agent should penetrate tubules better. PMID- 11199799 TI - Effects of the Nd:YAP laser on coronal restorative materials: implications for endodontic retreatment. AB - With new wavelengths that allow light transmission by optical fibers, the laser is now often used in endodontics either during treatment or retreatment. The aims of this study were to (i) specify the effects of laser irradiation on restorative materials in terms of topographic effects and (ii) describe different protocols for the first steps of retreatment. The laser used in this study was an optical fiber Nd:YAP (Lokki dt, Vienne, France) with a wavelength of 1.34 microns. Samples of the following restorative materials were prepared: amalgam, composite, permanent and temporary cements, and prosthodontic alloy. The handpiece of the Nd:YAP laser was fixed perpendicular to the surface of the different preparations. All trials were performed with the fiber tip either in contact with or at a distance of 2 mm from the material. The surface effects in all cases were (i) the creation of craters in the center of the lased areas, (ii) a border of fusion material at the edge of the craters, and (iii) cracks or fractures at a distance from the target areas. For the cements, amalgam and composite, the effects included a projection of material from the center to the edge of the lased area and/or the apparent photovolatization of light particles. For all materials the laser induced deeper absorption in the areas of direct contact than when it was held at a distance. This suggests that the fiber should be in contact with the restorative material for lasing in the straight part of the canal when the objective is either to pass through the material or alongside it between material and tooth. If the practitioner cannot determine the direction of the curve of the canal, lasing should be performed at a distance to weaken the material and thus permit more efficient use of an ultrasonic device. Lasing should in all cases be performed under close X-ray monitoring. Provided that sufficient caution is used, the laser may be helpful in removing restorative materials during retreatment. PMID- 11199800 TI - Isolation of Enterococcus faecalis in previously root-filled canals in a Lithuanian population. AB - The occurrence of Enterococcus faecalis in root canals of previously root filled teeth with apical periodontitis requiring retreatment was studied in Lithuanian patients. Twenty-five asymptomatic teeth were included in the study. Avoiding contamination microbiological samples were taken from the canals before and after preparation and irrigation with sodium hypochlorite and EDTA. Microbes were isolated from 20 of 25 teeth. E. faecalis was isolated from 14 of those 20 culture positive teeth, usually in pure culture or as a major component of the flora. Second samples taken after preparation revealed growth in 7 of the 20 teeth. Five of the seven cases were E. faecalis in pure culture. Isolation of E. faecalis was not related to the use of any particular root filling material in the original root filling. The results indicate that, rather than previous chemical treatment, it is the ecological conditions present in the incompletely filled root canal that are important for the presence of E. faecalis in these teeth. PMID- 11199801 TI - Quantitative analysis of catecholamines in human dental pulp. AB - Catecholamines are important elements of neuroendocrine regulation, and their concentrations in dental pulp are of interest. Two groups of teeth were used in this study: (i) healthy teeth and (ii) periodontally diseased teeth. After the processing of dental pulp obtained from the extracted teeth, the samples were analyzed in a computer-controlled Merck-Hitachi HPLC system at 280 nm wavelength. The external and internal standard methods of the HPLC Manager Program were used for validation. In healthy teeth the norepinephrine level of dental pulp was 4.86 +/- 0.96 micrograms/g, whereas the epinephrine level was 8.1 +/- 1.18 micrograms/g. In periodontally diseased teeth norepinephrine and epinephrine levels were significantly higher (p < 0.01) at 13.98 +/- 21.13 micrograms/g and 1.42 +/- 0.32 micrograms/g, respectively. Dopamine could not be demonstrated in 87% of the pulps. Summing up we succeeded in demonstrating norepinephrine and epinephrine in human pulp, but in most cases we could not demonstrate dopamine. Further investigations are needed on pulp tissue infected because of caries. PMID- 11199802 TI - Molecular epidemiology and association of putative pathogens in root canal infection. AB - The purpose of this study was to investigate the epidemiology of putative pathogens in root canals with apical periodontitis and to determine the associations among the putative pathogens. Eighteen symptomatic and 20 asymptomatic teeth from 36 subjects were studied. This research was performed with polymerase chain reaction and hybridization using rRNA-based oligonucleotide probes. The most frequently found species was Fusobacterium sp. (68.4%), followed by Peptostreptococcus micros (44.7%) and Porphyromonas gingivalis (26.3%). Sixteen teeth (42.1%) contained one or more species of the selected black pigmented bacteria. Bacteroides forsythus and Treponema sp. were detected in 8 teeth and 6 teeth, respectively. Among the analyzed bacteria, significant relationships were shown in the combination of B. forsythus/P. gingivalis and Treponema sp./P. gingivalis. There was no significant association between any bacteria and any symptoms. PMID- 11199803 TI - Structure and chemical composition of an experimentally formed apical barrier after the application of calcium-glycerophosphate. AB - Transformation in the structure and composition of calcium-glycerophosphate (Ca GP) was investigated using a scanning electron microscope fitted with an energy dispersive X-ray microanalysis (EDX) system. Ca-GP was packed inside roots that were subsequently implanted into the mandibles of rats to stimulate the formation of an apical barrier. Scanning electron microscopic observations of packed Ca-GP revealed three types of structures: globular aggregates, plate or flake-like aggregates, and granular aggregates. The average Ca/P molar ratios of EDX by area mode--postoperatively obtained at days 1, 3, 5, and 7--were 1.300, 1.533, 1.472, and 1.495 (analytic area: 0.01 to 0.03 mm2) and those of EDX by point mode were 1.220, 1.451, 1.487, and 1.467 (analytic point: 0.05 micron 2). The magnesium (Mg) weight percentage was found to be approximately 1.9 at days 3, 5, and 7, similar to Mg-substituted whitlockite. These findings suggest that Ca-GP are transformed, over a period of 3 days into Mg-substituted whitlockite as a result of being hydrolyzed by tissue fluid. PMID- 11199804 TI - A survey of participation in managed care programs by endodontic specialists. AB - A survey was published in the Quarterly Survey of Dental Practice (QSDP) Special Topics that dealt with contractual agreements in dentistry. This survey evaluated general dental practitioner participation apart from that of dental specialists in general. The Quarterly Survey of Dental Practice survey was modified and used in the present study to specifically determine the participation by endodontists in various contractual insurance agreements, including Preferred Provider Organization and Health Maintenance Organization programs. A 10% sample of practicing endodontists was randomly selected to participate in this survey. Questionnaires (331) were sent out, and 229 or 69% were returned. Total participation by endodontists responding to this survey in any Health Maintenance Organization and/or Preferred Provider Organization insurance plans was 31.3%; however the total percentage of patients treated under these insurance plans was only 6.6%. These results were similar to those in the 1994 survey in which it was shown that 27% of the general dental practitioners and 41% of the dental specialists participated in one or more of these insurance programs and treated respectively, 5% and 9%, of their patients under these plans. Although participation in various managed care programs by endodontists in this survey was close to one-third, the total number of patients treated under these plans was low. Overall patients treated under fee-for-service arrangements by endodontists responding to this survey formed 85.3% of their patient pool. It does not appear from the results of this survey that managed care insurance has a significant impact on the practice of endodontics. It can be postulated that endodontists are unwilling to accept more than a small reduction in fees to join managed care plans, and they also desire to retain full control of their dental practice. PMID- 11199805 TI - Measurement of endodontic file lengths: a density profile plot analysis. AB - The purpose of this study was to evaluate measurements of endodontic files of known length and diameter using a density profile plot analysis of digital images. Ten single-rooted teeth with relatively straight roots in cadaver specimens were used. The crowns of the teeth were removed and a rectangular orthodontic wire, 5.13 mm in length, was placed horizontally on the occlusal surface to serve as a calibration reference point. The #8, #10, #15, and #20 FlexOFiles were measured to the nearest 0.5 mm and then placed to four working lengths that terminated within the apical third of each root. A GE X-ray unit and a Schick CDR #2 sensor were used to digitally acquire 160 images. The digital images were placed in random order and an independent, blinded investigator determined the file length using a density profile plot analysis. The measurements generated by the histogram analysis (experimental) were compared with the original clinical measurements. The paired t test, intraclass correlation coefficient, and the Bradley-Blackwood test were used to assess reliability. The results revealed that the means of the experimental measurements of all file sizes were within 0.5 mm of the known lengths and were always shorter than the known lengths. Also, the larger the file size the less deviation from the known lengths: #20, -0.16 mm (p = 0.0001); #15, -0.21 mm (p = 0.0001); #10, 0.34 mm (p = 0.0001); and #8, -0.45 mm (p = 0.0001). This study demonstrated that the density profile plot analysis might be a useful adjunct for the measurement of endodontic file lengths on a digital image. PMID- 11199806 TI - Accessory branch of the mental nerve. AB - This case report presents a surgical case in which an accessory branch of the mental nerve exited the mandible distal and slightly superior to the mental foramen. Careful manipulation of the surgical site allowed proper identification of the mental nerve, and the accessory branch and permanent nerve damage was avoided. PMID- 11199808 TI - Diagnostic thermal pulp testing: a technique. AB - This paper presents a technique for thermal testing that has proved useful where the usual diagnostic routine was unable to clarify the problem. PMID- 11199807 TI - Hemangioma of the mandible presenting as a periapical radiolucency. AB - A case of an hemangioma of the mandible in a 53-yr-old female patient is presented. The lesion was removed, and no atypia or mitotic cells were found. The excision was curative, and the overall prognosis was excellent. A differential diagnosis of radiolucent periapical lesions of the mandibular symphysis is presented. PMID- 11199809 TI - Dyskinesia in Parkinson's disease. Pathophysiology and clinical risk factors. AB - Development of dyskinesia is a common phenomenon during the long-term course of Parkinson's disease. During the last few years some but not all pathogenetic mechanisms causing dyskinesias in PD have been better understood. Severity of Parkinson's disease and levodopa dosing are the main clinical risk factors. Most concepts underline the significance of pulsatile D1-receptor stimulation for the development of dyskinesias. The interactions between D1- and D2-mediated STR-Gpi pathways and co-localized neuropeptides are important but not fully understood. Glutamatergic overactivity might also be a significant pathogenetic factor. According to these pathophysiological concepts, therapeutic strategies focus mainly on continuous postsynaptic DA-receptor stimulation by long acting DA agonists or highly selective D2 agonists. Another strategy is the use of NMDA antagonists. PMID- 11199810 TI - Long-term treatment with dopamine agonists in idiopathic Parkinson's disease. AB - Long-term treatment studies with any antiparkinsonian drug are rather limited. Especially, double-blind, randomized and multicenter studies do not exist except for some rare exceptions. Nonetheless, such studies are mandatory to prove certain therapy regimens. This overview reports on the comparison between dopamine agonists and levodopa. There are open studies comparing bromocriptine, lisuride, pergolide with levodopa which demonstrate that the use of dopamine agonists in monotherapy or combination with levodopa decreases the percentage of patients who develop dyskinesias compared to levodopa only. A long-term study was performed with cabergoline (3 years) which was extended in an open trial for another 2 years and which underlined the above mentioned observation. In a very recent study, ropinirole was compared with levodopa. This double-blind study spans 5 years and shows that about 30% of patients were able to stay for 5 years on ropinirole monotherapy, that withdrawal rate was not higher in the dopamine agonist group and that the side effects were similar in the levodopa and the ropinirole group. The major finding of this study was a very low dyskinesia rate when treating patients with ropinirol alone. Thus, this study underlines our therapy concept which advocates the early use of dopamine agonists in IPS. PMID- 11199811 TI - SPECT and PET imaging of the dopaminergic system in Parkinson's disease. AB - This paper gives an overview of the clinical importance of SPECT and PET imaging of the dopaminergic system in the differential diagnosis and for the determination of the progression rate of Parkinson's disease (PD). D2 receptor imaging can help to differentiate multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) from PD. In patients treated with neuroleptics it is possible to determine the rate of striatal D2 receptor blockade using this technique. This occupancy rate parallels the occurrence of parkinsonian side effects. Its measurement helps in the selection of newer atypical neuroleptics, which can be used to treat drug-induced psychosis in PD because they do not aggravate parkinsonian symptoms. Imaging of dopaminergic neurons with [123I]beta CIT SPECT or [18F]DOPA PET is a way to visualize and quantify the nigrostriatal dopaminergic lesion in PD. Findings correlate with clinical rating scales and demonstrate the feasibility of detecting the preclinical lesion in patients with hemiparkinson or familial PD. [123I]beta-CIT SPECT can easily distinguish patients with essential tremor and patients with "lower body parkinsonism" due to a subcortical vascular encephalopathy. MSA and PSP cannot be separated from PD with this method alone. Longitudinal studies with [123I]beta-CIT SPECT and [18F]DOPA PET can quantify the progression rate in PD. SPECT results from our own group show a low rate of progression in patients with a long duration of disease and a more marked progression rate in patients with shorter disease duration. In the former group regions in the striatum with higher beta-CIT binding at the time of the first SPECT scan decline faster than regions with lower binding. These findings suggest a curvilinear course of progression which starts at different time points in different striatal regions and which levels off after several years of disease duration. These findings are in line with data from PET studies and underline the importance of an early start of neuroprotective strategies. Preliminary data from PET and SPECT studies in early PD suggest that dopamine agonists might have a slight neuroprotective effect and might slow down the rate of progression of the disease. PMID- 11199812 TI - Parkinson's disease and sleep. AB - There are many reasons for patients with idiopathic Parkinson's disease to develop sleep disorders and subsequent daytime sleepiness. Important causes are reduction of total sleep duration and sleep efficiency, and an increase in respiratory and motor arousals. This daytime sleepiness at first glance seems different from the "sleep attacks" which caused motot vehicle mishaps reported recently in persons taking pramipexole and ropinirole. There is, however, only little evidence that we deal with a new phenomenon in a new clinical situation, i. e. cataplexy-like attacks after high doses of new non-ergot dopamine-agonists. Until now there is no single case of a proven cataplexy on one hand, and older dopamine agonists like pergolide as well as L-Dopa + carbidopa have been reported to induce sudden onsets of sleep, too. PMID- 11199813 TI - Effects of parkinsonian medication on sleep. AB - Patients suffering from Parkinson's disease (PD) often report about sleep disorders and excessive daytime sleepiness. To some extent, motor disabilities or neural degeneration of sleep modulating structures may be responsible for these effects. Depressive disorders also contribute to the occurrence of insomnia and daytime sleepiness. Nevertheless, dopaminergic, anticholinergic, and other drugs used in PD have a great impact on sleep/wakefulness mechanisms. They may indirectly improve or worsen sleep by changing motor symptoms such as akinesia, hyperkinesia, or tremor. Although their is only little information on the complex regulation of vigilance, it is well known that monoaminergic and cholinergic drugs could influence it directly. Data from animal experiments and clinical experiences led to the hypothesis of a biphasic influence on sleep by dopaminergic substances: small doses of L-Dopa e. g. appear to improve sleep whilst higher doses led to insomnia. Different dopaminergic receptor types or changes in receptor sensitivity may explain these phenomena. Dopaminergic and anticholinergic drugs suppress REM sleep. Recently, initial data on 'sleep attacks' after pramipexole or ropinirole treatment were published. Our preliminary results using 24 h polygraphic recordings showed excessive daytime sleepiness in patients taking ropinirole and L-Dopa which disappeared when changed to ropinirole monotherapy. Sleepiness did never appear as an irresistible attack. Current hypotheses on this topic are reviewed. PMID- 11199814 TI - Parkinson's disease and the ability to drive. AB - Criteria for assessment of the ability to drive in Germany are based on guidelines published by the Gemeinsamer Beirat fur Verkehrsmedizin and incorporated into the legislation. Decisions relating to the ability to drive must always be taken on an individual basis. In parkinsonian patients the ability to drive is very often impaired by motor symptoms, psychiatric complications, multimorbidity, increased daytime sleepiness and especially by cognitive disturbances. Increased daytime tiredness is common in Parkinson's disease with additional sedative effects of all dopaminergic agents (e. g., pramipexole, ropinirole). Unwanted falling asleep (e. g., at the wheel) can be avoided if notice is taken of the early signs of tiredness. A recommendation is included how to advise patients with Parkinson's disease treated with a dopamine agonist regarding the ability to drive. PMID- 11199815 TI - Costs in the treatment of parkinsonism. AB - Parkinson's disease imposes a considerable economic burden on our society. Apart from the direct costs for therapy, the indirect costs of the disease are estimated to be substantially higher. Unfortunately, only the high costs of current medication are usually considered, when financial aspects are discussed. An ideal therapy should ameliorate the symptoms of the disease and achieve a high quality of life. but the prognosis should also be improved. Cost estimates have to be extended throughout the course of the disease. We recommend a treatment schedule which is expected to result in a favorable cost profile when the entire course of the disease, is considered. L-Dopa monotherapy in working patients is obsolete. During the course of the disease dopamine agonists, amantadine, budipine, COMT inhibitors and selegiline will be used. PMID- 11199816 TI - Workshop I: Parkinson's disease and sleep--results of the group discussion. AB - The group agreed on the facts that unwanted sleep onset has been observed after non-ergot as well as ergot dopamine agonists, that patients on these drugs need to be warned, that patients who have experienced sleepiness already must not drive a car unless the dosage is lowered and sleepiness has vanished, that a genetic predisposition for narcoleptic cataplexy has to be ruled out, that predictors of so-called sleep attacks need to be explored individually with the help of sleepiness scales and collectively in a careful study, respectively. PMID- 11199817 TI - Workshop II: "neuroprotection"--the Lugano consensus. AB - Consensus could be reached that there is overwhelming evidence of preclinical neuroprotection. However, the evidence of neuroprotection/neurorescue under clinical conditions is limited. Lessons from clinical trials designed to show neuroprotection (selegiline, amantadine, dopamine agonists) demonstrate that with the drugs available neuroprotection/neurorescue has to start as early as possible. A PET-controlled clinical trial with ropinirole shows that there seems to be a good chance for neuroprotection in the early phase of Parkinson's disease in patients treated from the very beginning of the disease while there is no such benefit in patients with a late start of a neuroprotective therapeutic strategy. Also long-term neuroprotection cannot be reached. Complicating factors to demonstrate clinical neuroprotection are discussed. PMID- 11199818 TI - Workshop III: late motor complications of Parkinson's disease. AB - The aim in the current treatment of Parkinson's disease is to delay L-Dopa administration and to keep the L-Dopa dosage as low as possible. Such a treatment strategy can delay the onset of late motor complications and reduce their severity. L-Dopa remains the most potent anti-parkinsonian medication, but its use for the initial therapy of Parkinson's disease is limited to elderly patients. In all other cases, dopamine agonists, budipine, amantadine and selegiline are primarily used. With the occurrence of late motor complications continuous dopamine receptor stimulation becomes essential. In this situation, combination therapy has to be individualized, with dopamine agonists playing a key role. In addition, COMT inhibitors, budipine, amantadine and selegiline may be used. Anticholinergic drugs are of very limited importance in the current treatment of Parkinson's disease. PMID- 11199819 TI - Workshop IV: drug treatment guidelines for the long-term management of Parkinson's disease. AB - An attempt was made to establish a decision algorithm for the treatment of idiopathic Parkinson's disease at various stages and in different subgroups such as akinetic-rigid or tremor dominance type. We suggest treating young patients with selegiline and a dopamine agonist. In the tremor dominance type we use either budipine or a dopamine agonist. Due to levodopa-induced dyskinesia, we try to avoid levodopa in the early stages of the disease and use it only later in more advanced situations in a combination therapy with dopamine agonists. Since IPS is not only based upon dopamine deficiency but also on resulting glutamatergic overstimulation, we advocate the use of a glutamate antagonist such as amantadine or budipine. Catechol-O-methyl inhibitors are very helpful when wearing-off occurs. Anticholinergics are only used in the early stages of tremor dominant IPS because we fear enhancing the risk of dementia. PMID- 11199820 TI - Is there neuroprotection in Parkinson syndrome? AB - Parkinson's disease (PD) is a neurodegenerative disorder of the aging population with unknown etiopathogenesis. It is assumed that the underlying pathobiochemical processes comprise multifactorial and multigenetic disturbances leading to a progressive and devastating disorder without remission. Subtypes exist suggesting that "PD" is a spectrum disorder with variations in the cascade of pathobiochemical and genetic events. Neuroprotective endogenous processes are lost at the very beginning of PD. Supplementation of substances with neuroprotective and/or neurorescue capacity is eminent for future therapeutic strategies. MAO-B inhibitors, NMDA-receptor antagonists and dopamine receptor agonists fulfill such a criterion in preclinical studies while there is no clear evidence for clinical neuroprotection. However, PET-controlled studies comparing L-DOPA-treated and ropinirol-treated PD patients give evidence for the "concept of neuroprotective treatment strategies". PMID- 11199821 TI - Lessons, labels, license, uses, and the FDA. PMID- 11199822 TI - Diode laser (980 nm) in oral and maxillofacial surgical procedures: clinical observations based on clinical applications. AB - OBJECTIVE: The aim of this study was to examine the wound healing of soft tissue after the application of a diode laser (980 nm) in oral surgical procedures. SUMMARY BACKGROUND DATA: Like the CO2 laser, the diode laser can be used for soft tissue surgery without extensive experience in the field of oral surgical. METHODS: A diode laser was used to treat a variety of oral soft tissue lesions in 22 patients. The oral surgical procedures included removal of soft tissue tumors, frenectomies, excision of gingival hyperplasias, vestibuloplasties, hemangioma removal, and periimplant soft tissue surgery. The laser was used in both pulsed and continuous modes, with and without contact to the tissue. Intraoperative and postoperative clinical observations are reported. RESULTS: Our preliminary clinical findings include sufficient hemostasis and precise incision margin with all of the surgical procedures. The coagulation properties, associated with the use of a diode laser, were particularly beneficial during removal of vascular lesions. The postoperative advantages, i.e., lack of swelling, bleeding, pain or, scar tissue formation, and the good wound healing were observed in all of the clinical applications and were dependent only on the laser physical parameters used. CONCLUSIONS: The clinical application of the diode (980 nm) laser in oral and maxillofacial surgical procedures seems to be of beneficial effect for daily practice. PMID- 11199823 TI - The fluidodynamics of potentially neoplastic plumes produced by medical lasers: first quantitative non-tissue-specific measurements using PMMA samples (phase I). AB - OBJECTIVE: This study has two goals: (1) to identify and discuss key factors that contribute to the spread of potentially dangerous plumes chaotically in the vicinity of patients following surgery with medical lasers and (2) to recommend safety procedures for surgical staff members based on the measurements, analysis of results, and conclusions. SUMMARY BACKGROUND DATA: In the past years, only a few studies have attempted to quantify the risks associated with routine exposure to plumes generated by medical lasers used to treat malignant tissue. The invasive thermodynamic sublimation processes following beam-tissue interaction generate plumes, which also contain particles of tumoral tissue not completely burned by the laser beam itself. These fumes can also be chemical by-products produced by normal tissue combustion. In both cases they retain a certain degree of malignancy (mainly depending on the type of tumor and by-product), which could result in spreading metastasis in the respiratory system of the surgical staff members and of the patient following inhalation. Only a few studies in the literature discuss this phenomenon, but all of them demonstrate clearly that current fume evacuator systems based on fixed air suctioning probes near the tip of the laser's focal head do not guarantee sufficient aspiration of the total dangerous gas volume (mixture of air and fumes) generated during complete surgical intervention. METHODS: The author has made several measurements of the size, shape, dimension, and speed of the plumes associated with crater development in polymethylmethacrylate (PMMA) blocks exposed to a pulsed CO2 laser beam. The laser device has been optimized for visualization via the thermocamera and each smoke burst was measured as follows: 2.5 and 5 inch focal lengths, peak energy of 33 mJ, TEM00 mode, 4 Hz, pulse width tp = 10 msec, and total exposure time te = 10 sec have been used to irradiate 3 x 2 x 3 cm3 PMMA blocks. From a pure thermochemical point of view, PMMA has been used as the gross first approximation medium for a large variety of biological tissues because the aim is to provide a global non-tissue-specific modeling rather than a very detailed investigation of the large variety of possible combinations of tissues exposed to the laser beam. This part of the study is necessary and it will be addressed in Phase II of this project. RESULTS: A quantitative description of the dynamic process present in the production of plumes with PMMA samples has been obtained along with the quantification of seven key parameters, such as ejection velocities and plume size, which accurately describe the process itself. CONCLUSIONS: Although this can be only a first approximation study, its results provide a very good idea about the orders of magnitude of the key parameters involved in the processes and dynamics of global plume production. The author suggests how these conclusions can be extrapolated for in vivo applications and can be used as recommendations to design new suctioning devices aimed at increasing safety in the operating room. PMID- 11199824 TI - Treatment of cervical dentin hypersensitivity by various methods using pulsed Nd:YAG laser. AB - OBJECTIVE: The purpose of this study was to evaluate the results of two irradiated regions, the cervical and apical, for cervical dentin hypersensitivity treatment using pulsed a Nd:YAG laser with or without black ink. SUMMARY BACKGROUND DATA: There has been no reports on the irradiated area(s) except the cervical region for dentin hypersensitivity treatment using pulsed Nd:YAG laser. METHODS: A total of 180 teeth diagnosed with cervical dentin hypersensitivity in 54 (39 females, 15 males, aged 21 to 73) healthy adult patients were included in this study, and teeth were randomly divided into four groups of 45 each. Sensitivity was rated using a blast from a fully depressed air syringe on a four grade scale both before and up to 2 months after laser treatment. The effectiveness was evaluated on the change in the degree of hypersensitivity after laser treatment. The tooth surfaces in groups 1 and 2 were observed by the replica model method using scanning electron microscopy (SEM). RESULTS: The methods of irradiation at the cervical regions were better than those at the apical regions except for the period 2 months later. The laser effect was enhanced by black ink at both areas. The effective (excellent and good) rate was decreased depending on the time in every group. SEM observation at the tooth surfaces from group 2 showed that dentinal tubules were occluded or narrowed after laser irradiation. CONCLUSIONS: These results show that the method of irradiation by a pulsed Nd:YAG laser at cervical regions with black ink is the most effective for cervical dentin treatment of hypersensitivity and recurrence by this method is less than in other methods. PMID- 11199825 TI - A study on the morphological changes of the rat mandibular bone with TEA CO2 laser. AB - OBJECTIVE: The purpose of this study was to investigate the morphological changes of the bone structure induced by transversely excited, atmospheric TEA pressure CO2 laser irradiation. Moreover, the healing process at 3 weeks was also observed. SUMMARY BACKGROUND DATA: It has been demonstrated that dental hard tissue can be removed by a long pulse of TEA CO2 laser irradiation with minimal thermal damage. However, there are few studies on the morphological changes of the TEA CO2 laser on bone tissue. METHODS: The TEA CO2 laser was irradiated on the surface of the rat mandibular bone under the following irradiation conditions: wavelength, 10.6 microns; output, 95 mJ/pulse; pulse repetition rate, 1 Hz; irradiation time, 7.5 microseconds/shot; spot size, 0.8 x 1.5 mm; energy density, 7.9 J/cm2. Histological and scanning electron microscopic examinations were performed. RESULTS: In the stereoscopic examination, a defect with clean-cut margins was produced. In the light microscopic examination, a basophilic line at the bottom of the defect was noted. Examining the defect with SEM, a smear-like appearance and cone structures were found. In the histological examination, a healing process by formation of new bones at the junction site was recognized. CONCLUSIONS: These findings suggest that it is possible to remove bone tissues by TEA CO2 laser irradiation. However, a particle-like structure associated with a basophilic line and melted surface indicated that some thermal damage was produced during the laser irradiation. PMID- 11199826 TI - Increasing the width of periodontal attached gingiva using an Nd:YAG laser and GTM: results of a clinical study. AB - OBJECTIVE: Demonstrate a new technique to increase the width of keratinized gingiva using a biological membrane material in place of donor tissue. SUMMARY BACKGROUND DATA: Most current surgical techniques require donor tissue as a graft to increase keratinized gingiva, which results in a second trauma site for the patient. METHODS: Using an Nd:YAG laser with contact tip. Laser energy at settings of 3.0-6.0 W continuous mode. Local anesthetic, lidocaine 2% and epinephrine 1:100,000, was administered. A mucogingival flap was made to the periosteum and reflected, followed by placement of a biological membrane, and sutured into place, over the surgical site. RESULTS: A total of 20 sites were treated on 20 different patients of 15 mandible and 5 maxillary sites. The average increase for all sites was 3.8 mm of keratinized gingiva per site. No adverse events (e.g., bleeding, allergic reactions, abscesses, or pain) after any of the treatments were noted during the entire observation. The treatment procedure led to significant improvements in width of gingiva. The 20 patients were pleased with this new technique using the Nd:YAG laser with contact tip. CONCLUSION: It may be concluded that the new procedure provides significant increase of keratinized gingiva with the advantage of minimal morbidity and pleasing cosmetic results. Further clinical studies are needed to compare traditional procedures with the laser augmentation technique. PMID- 11199827 TI - Acquired acid resistance of dental hard tissues by CO2 laser irradiation. AB - OBJECTIVE: This investigation was performed to evaluate the effect of CO2 laser irradiation on the acquired acid resistance of dental hard tissues to artificial caries-like formation and the ultrastructure of lased areas was morphologically investigated in vitro. SUMMARY BACKGROUND DATA: In recent years, many studies have been carried out to evaluate the effect of the CO2 laser on the enhanced resistance to artificial caries formation of enamel. However, a limited number of papers concerning its effect on dentin have been published. METHODS: A CO2 laser of 10.6 microns wavelength was used to irradiate human enamel and dentin samples from 20 extracted human molar teeth, and samples were subjected to 2 microliters of 0.1 M lactic acid solution (pH 4.8) for 24 h at 36 degrees C. The parts per million (ppm) of calcium ion (Ca2+) dissolved in each solution was determined by atomic absorption spectrophotometry and the morphological changes were investigated by scanning electron microscopy (SEM). RESULTS: The lowest mean Ca2+ ppm was recorded in the samples irradiated at 3 W, followed by 2 W, 1 W, and unlased samples. SEM observation showed that the lased areas were melting with solidification of the smear layer. Even after acid demineralization, the lased surfaces were almost unchanged. CONCLUSIONS: The results of this study suggested that CO2 laser irradiation could sufficiently melt and solidify the enamel and dentin surfaces and thus enhance resistance to artificial caries-like formation. PMID- 11199828 TI - Ablation depths and morphological changes in human enamel and dentin after Er:YAG laser irradiation with or without water mist. AB - OBJECTIVE: This investigation was performed quantitatively to determine the ranges of ablation and to evaluate the morphological changes in human enamel and dentin irradiated by Er:YAG laser with or without water mist. SUMMARY BACKGROUND DATA: Recently, several infrared lasers have been introduced in the dental clinic to remove carious dental hard tissues in anticipation of replacing the high-speed dental drill. Among them, the Er:YAG laser has shown the most promise for hard tissue ablation. METHODS: An Er:YAG laser was used to ablate human dental hard tissues using a pulse energy that ranged from 100 to 400 mJ at a frequency of 2 Hz for 5 seconds. Ablation rates with or without water mist at different pulse energies were measured, and the morphological changes on enamel and dentin were also investigated by stereomicroscopy and scanning electron microscopy (SEM). RESULTS: The relationship between ablation depths and energies was almost linear at both enamel and dentin samples. The irradiation with water mist reduced the ablation depths, but only minimally, when compared to those irradiated without water mist. Morphological findings by SEM indicated that Er:YAG laser irradiation with water mist could produce the cavities without signs of thermal damage to the surrounding enamel and dentin. CONCLUSIONS: The results of this study suggest that addition of a fine water mist directed at the ablation sites does not greatly decrease the ablation, and does not cause any carbonization and melting in the surrounding dental hard tissues. PMID- 11199829 TI - Three years of clinical evaluation of endodontically treated teeth by 15 F CO2 laser microprobe: in vivo study. AB - OBJECTIVE: Evaluation of the efficiency of 15 F CO2 laser microprobe, in cases of periapical lesions. The elimination of the pathological reaction caused by certain species of bacteria by reduction of reinfection and stimulation of osteogenesis. SUMMARY BACKGROUND DATA: Until now, no suitable delivery fiber existed for CO2 laser endodontic radiation in the apical region where it is most difficult to eliminate the pulp tissue using conventional methods. To overcome this problem, Sharplan Lasers designed a microprobe that reaches closer to the apex, distributing the energy density to a smaller area of the root canal, thus favorably increasing the thermal effects. METHODS: The study was conducted on 900 teeth, corresponding to 1512 root canals, divided in two groups. Four hundred sixty-eight were new cases, carefully selected according to strict parameters such as wide periapical translucency over 1 mm, supported by digital x-ray, with a lesion of 3 mm and more. All root canals were mechanically prepared in the conventional method up to size 35, Physiological saline solution served as rinsing solution and the root canals were treated by 15 F CO2 laser microprobe for 60 pulses repeatedly. The temperature at the surrounding tissue of the root did not exceed 38 degrees C. RESULTS: Filling of the canal was possible at the same appointment, without antibiotic treatment. Four hundred thirty-two of the cases, which were referred to us by other dentists after an unsuccessful treatment according to the classic therapy, were treated by the same laser therapy. Follow-up was performed by clinical examination, and a digital x-ray was taken, during and after treatment as well as after 3, 6, 9, and 12 months. CONCLUSIONS: There is a 98% success rate in both study groups, according to objective criteria for successful treatment including reduction of apical translucency after 2-6 months, freedom from clinical complaints, and no need for periapical surgery. PMID- 11199830 TI - A comparison of three methods for the diagnosis of sound, stained, and carious dentine: conventional, mechanico-acoustic, and laser-acoustic methods. AB - OBJECTIVE: The authors examined two novel and objective methods for diagnosing stained, carious, and sound dentine, a mechanico-acoustic method and a laser acoustic method, and compared these with the conventional but subjective method of visual and tactile assessment using a dental probe. SUMMARY BACKGROUND DATA: It is accepted clinical practice to leave stained but relatively firm dentine on the pulpal surface of dental cavities prepared for restoration. The problem for the clinician is in deciding which dentine is carious and which is stained but acceptable to be left in situ. There is no objective method for making this decision, it is usually made on the basis of visual examination and tactile assessment using a dental probe. METHODS: The authors used Fourier analysis of acoustic waves arising from mechanical (dental probe) or laser (Er:YAG laser) interaction with the tooth surface and compared the results with the subjective assessment of the same tissue surfaces as judged by a clinician using visual and tactile assessment with the same dental probe. RESULTS: The results showed that both the mechanico-acoustic and laser-acoustic methods were more accurate and more objective than the conventional visual/tactile method and that an analysis of both the integral and spectral signals produced by the Er:Yag Laser (lambda = 2.94 microns) allowed for a more accurate diagnosis than the other two methods examined. CONCLUSIONS: Both mechanico-acoustic and laser-acoustic methods of diagnosing sound, stained, and carious dentine were more accurate than the subjective visual/tactile method using a dental probe. The laser-acoustic method was the most accurate of all of the methods compared. An advantage of the laser acoustic method is that it could be included into the actual process of cavity preparation when using an Er:YAG laser, providing an objective and more accurate assessment of the nature of the remaining dentin and may therefore be more economic of time, eliminating the necessity for constant cessation of drilling to assess the nature of the target tissue. PMID- 11199831 TI - Study on apical leakage of the teeth after argon laser treatment and obturation. AB - OBJECTIVE: This study was performed to compare the apical leakage degree after laser treatment and obturation with that without laser treatment, and to evaluate the efficiency of argon laser irradiation in removing debris and smear layer from the prepared root canal walls in vitro. SUMMARY BACKGROUND DATA: There has been no report of laser effect on apical leakage after laser treatment and obturation. METHODS: Fifty-six human extracted single root teeth were used in this study. Teeth were divided into four groups of 14 teeth each and prepared up to a #60 K file size at 1 mm short of the apical foramen using a step-back technique. Argon laser at the wavelength of 470 nm and at the output of 0.3 W was irradiated at apical stop for 1, 2, or 3 seconds at the continuous mode. In each group, ten teeth for the microleakage study were obturated and immersed in rhodamine B solution for 48 hours at 37 degrees C, and the others were used for the observation by scanning electron microscopy (SEM). All teeth were bisected longitudinally and observed by stereoscopy or SEM. RESULTS: The apical leakage degree after laser treatment and obturation was reduced compared to that in the control, but not significantly (p > 0.05). However, debris and smear layer in the laser-treated groups were removed from apical stop even at low energy density. CONCLUSIONS: These results suggest that apical leakage after argon laser treatment is not reduced significantly, but that argon laser is useful for removing debris and smear layer from root canals. PMID- 11199832 TI - Characterization of enamel and dentin response to Nd:YAG picosecond laser ablation. AB - OBJECTIVE: We investigated the main characteristics of human dental tissue under Nd:YAG picosecond laser ablation. SUMMARY BACKGROUND DATA: The use of ultrashort laser pulses for teeth ablation prevents overheating and is an alternative for mechanical material removal; it also minimizes the volume of damaged material. METHODS: Laser pulses of picosecond at 15 Hz repetition rates from a Q-switched and mode-locked Nd:YAG laser were focused on sound human molars for 30 seconds. Variation of light intensity in the pulse train allowed us to obtain drilled holes with different characteristics. Enamel and dentin surfaces were examined by optical and scanning electron microscope (SEM). The samples consisted of three sound human molars. The ablation rate was determined after taking an average of all samples. RESULTS: Images from the SEM showed an interesting contrast between the morphology of the ablated enamel and dentin regions. In enamel, the ablated region appears to be more superficial than in dentin. The dentin fragility normally causes cracks that originate in the ablated region. The ablation rates in both enamel and dentin demonstrate a saturation behavior as the laser intensity increases. Furthermore, the ablation rate in dentin is about eight times greater than in enamel for the same laser fluence. CONCLUSION: Our results show an important correlation between the surface morphology and the pulsed laser fluence, which is compatible to the ablation mechanisms presented when ultrashort laser pulses are used. PMID- 11199833 TI - "New lamps for old": technology dreams and risks. PMID- 11199834 TI - Skin resurfacing improved with a new dual wavelength Er:YAG/CO2 laser system: a comparative study. AB - OBJECTIVE: The efficacy of a new dual wavelength Er:YAG and CO2 laser system was tested for skin resurfacing results on rabbits' ears and human facial skin. The dual wavelength laser delivers simultaneous pulses of low-energy CO2 and high energy Er:YAG energies. Theoretically, combining the strengths of both laser types in one console should lead to improved clinical outcome. SUMMARY BACKGROUND DATA: The use of the laser for skin resurfacing and remodeling has dramatically increased over the past few years. The CO2 laser was the first laser to be used in this field, followed more recently by the E:YAG laser. Both lasers offer unique advantages and disadvantages. METHODS: The present study consists of an ear chamber experiment, conducted on eight rabbits, to examine vascular network formation, after laser resurfacing with a standard CO2 laser and the Er:YAG/CO2 laser. Resurfacing was also performed on human patients with the Er:YAG/CO2 laser and the results were compared with previously published results of CO2 laser resurfacing. RESULTS: Significant advantages, including an attenuation in the degree of edema and erythema and a shorter reepithelialization time compared to results with conventional CO2 systems, were observed with the Er:YAG/CO2 system. Improved tissue reorganization and good clinical results in nine of the ten patients (six ratings of "very good" and three "good") were observed. The clinical outcome of the remaining patient was rated as "fair." Minimal side effects were reported and observed in only three patients. The learning curve required to maximize the efficiency of the system is steep, however, requiring a thorough understanding of the different laser/tissue interactions associated with the two wavelengths. CONCLUSION: It is the authors' opinion that the dual wavelength Er:YAG/CO2 laser system offers a particularly efficient and flexible system to perform standard CO2 procedures for skin resurfacing with an improved clinical outcome, as well as other applications with the CO2 or Er:YAG energy delivered separately. PMID- 11199835 TI - "When the bough breaks". PMID- 11199836 TI - Morphological changes of rat mandibular bone with ArF excimer laser in vivo. AB - OBJECTIVE: The purpose of this study was to investigate the morphological changes of bone tissue by ArF excimer laser irradiation in vivo. SUMMARY BACKGROUND DATA: Recently, it has been demonstrated that soft and hard tissues can be removed by excimer laser irradiation with little thermal damage. METHODS: ArF excimer laser was irradiated on the surface of the rat mandibular bone using the following parameters: wavelength; 193 nm; output: 0.12 W; pulse repetition rate: 10 Hz; spot size: 1.0 x 4.0 mm; irradiation time: 90 and 120 seconds. The ablation depth was measured at 90 and 120 seconds. Furthermore, the irradiated surface was examined histologically using scanning electron microscopy (SEM). RESULTS: The relationship between ablation depth and irradiation time was almost linear. Macroscopically, the ArF excimer laser beam produced a defect with clean-cut margins without carbonization in the mandibular bone. Histologically, there was minimal evidence of thermal damage to the surrounding tissue. The bottom of the defect revealed a sawtooth appearance. In SEM observation, mosaic structures corresponded to the sawtooth structures observed with light microscopy. CONCLUSIONS: These findings suggest that it is possible to remove bone tissue using ArF excimer laser irradiation without thermal damage. The effectiveness of this laser can be attributed to the photoablation of the bone tissue. PMID- 11199837 TI - Diamond-shaped optical fiber delivery system. AB - OBJECTIVE: Physicians who use laser systems are looking for new fiberoptic delivery systems with better performance. We searched for a delivery system with high power and with a tip of high durability that may be reused many times. SUMMARY BACKGROUND DATA: The delivery systems currently found on the market can burn and break easily. The surgeon may either finish the surgery with a damaged delivery system, or have to switch to a new one during surgery, thus increasing the inconvenience and cost of the surgery. METHODS: Distal tips of fibers used with Nd:YAG and diode lasers have been shaped and polished according to their specific function, including excision, vaporization, and coagulation of tissue. RESULTS: We have developed several prototypes of optical fiber delivery systems, and in particular, we have developed a prototype of a delivery system, called the Diamond-Shaped Optical Fiber Delivery System, or Diamond. By making the tip of an optical fiber diamond shaped, we are able to obtain greater mechanical resistance than that of other delivery systems that were tested in our laboratory. In the Colorectal Unit, we applied it in surgical procedures such as perianal fistulectomy, hemorrhoidectomy, and excision of condilomata acuminata and pilonidal cyst and sinuses. During cutting and coagulating, the system performed well with no technical problems. CONCLUSIONS: A new delivery system (Diamond) gave satisfactory performance during surgical operations. Its main component, the diamond-shaped distal end, provided high durability and was reused many times, thus improving the quality of operations and reducing expenses greatly. PMID- 11199838 TI - Effects of Er,Cr:YSGG laser irradiation in human enamel and dentin: ablation and morphological studies. AB - OBJECTIVE: This investigation was performed to determine quantitatively the ranges of ablation and to evaluate the morphological changes in human enamel and dentin irradiated by Er,Cr:YSGG laser with or without water spray. SUMMARY BACKGROUND DATA: Recently, Er,Cr:YSGG laser has been introduced in dental clinics to remove carious dental hard tissues in anticipation of replacing the high-speed dental drill. METHODS: A total of 40 extracted human teeth were used in this study. An Er,Cr:YSGG laser was used to ablate human dental hard tissues with the output powers of 3 to 6 W. Ablation extent with or without water spray at different output powers was measured, and the morphological changes on enamel and dentin were also investigated by stereoscopy and scanning electron microscopy (SEM). RESULTS: The irradiation with water spray significantly (p < 0.001) increased the ablation depths compared to those irradiated without water mist. Morphological findings by SEM indicated that when irradiated without water spray, carbonization with brown or dark color was recognized in enamel or dentin, respectively. In addition, cavities with a molten lava-like appearance were produced and an irregular structure with many microholes was observed in dentin. CONCLUSIONS: These results suggest that during the Er,Cr:YSGG laser irradiation, water spray directed at the ablation sites increases the ablation depths and water plays an important role as an initiator of the ablation of dental hard tissues. PMID- 11199839 TI - The bactericidal effect of Nd:YAG, Ho:YAG, and Er:YAG laser irradiation in the root canal: an in vitro comparison. AB - OBJECTIVE: The aim of this study was to compare the antibacterial effectiveness of the Nd:YAG, the Ho:YAG, and the Er:YAG laser in infected root canals. SUMMARY BACKGROUND DATA: Lasers are gaining increasing importance in the field of endodontics. Numerous studies have shown the beneficial effects of laser treatment in disinfecting root canals. METHODS: In our in vitro experimental setup, 40 extracted and endodontically treated teeth were inoculated with a suspension of Escherichia coli and Enterococcus faecalis and then irradiated at standardized power settings. The disinfecting efficacy of each laser was proved by classical microbiological examination. RESULTS: This article highlights that all three lasers substantially decreased the bacterial population with only minimal differences in their microbicidal efficacy. At 1.5 W, the best results were obtained by the Er:YAG laser achieving a mean bacterial elimination of 99.64%, followed by the Nd:YAG laser (99.16%), and the Ho:YAG laser (99.05%). CONCLUSION: Our findings indicate that all three lasers act as strongly effective microbicides without causing unfavorable temperature rises at the settings used. They can thus be considered a valuable tool for root canal treatment. PMID- 11199840 TI - Nd:YAG laser influence on sound dentin bond strength. AB - OBJECTIVE: In the present study, the authors evaluated tensile bond strength of composite resin to dentin treated with Nd:YAG laser before and after bonding procedures. SUMMARY BACKGROUND DATA: Lasers have been widely used in dentistry and have contributed to the development of new technologies. Adhesive systems have been indicated for most dental procedures and have produced good results. Studies concerned with the combined use of this adhesive system was the subject of this study. METHODS: Thirty noncarious human anterior teeth, freshly extracted, for periodontal reasons, were used. After grinding the buccal dentinal surface until its exposition, specimens were separated into three groups and received the following treatments: (group 1) control--acid etching plus primer plus bond; (group 2) laser plus acid etching plus primer plus bond; (group 3) acid etching plus primer plus bond plus laser. Specimens of composite resin (Z100, 3M, Saint Paul, MN) were constructed on an inverted truncated 3-mm diameter cone mold. Tensile bond strength was performed using Instron Universal machine, at 0.5 mm/min speed. RESULTS: Analysis of variance (ANOVA) (p < 0.05) determined that the type of dentinal treatments used had an influence on tensile bond strength. Tukey's test, however, showed that group 1 (15.46) and 3 (15.67) had similar results both of which were higher than group 2 (4.57). CONCLUSIONS: Based on the results obtained, one can conclude that group 1 (without laser) and group 3 (laser after bonding) had similar results, both higher than those observed for group 2 (laser before bonding). These results indicate that more research is needed about how a hybrid layer is formed when laser radiation is used. PMID- 11199841 TI - In vitro study of the Nd:YAG laser effect on human dental enamel: optical and scanning electron microscope analysis. AB - OBJECTIVE: The Nd:YAG laser irradiation of dental enamel was evaluated in enamel demineralization experiments in a Streptococcus mutans culture media. SUMMARY BACKGROUND DATA: Previous studies had shown that a continuous wave Nd:YAG laser at an energy of approximately 67 mJ may induce an increased acid resistance in human dental enamel when exposed to severe demineralization conditions. METHODS: Enamel windows of 3 x 4 cm in the buccal surface were irradiated with a continuous wave Nd:YAG laser at a wavelength of 1,064 microns using energy densities of from 83.75 to 187.50 J/cm2. Enamel windows of 3 x 4 cm on the lingual surface served as control (without the laser irradiation). The enamel windows were then exposed to a Streptococcus mutans culture media at a temperature of 37 degrees C for 15 and 21 days. The laser effects and demineralization were examined both by optical microscopy and scanning electron microscopy (SEM). RESULTS: A comparison between the lased and the unlased windows of enamel showed fusion and recrystalization of the enamel and increased acid resistance in all groups irradiated with the Nd:YAG laser. On the other hand, the 3 x 4 delimited enamel surfaces from the control group (not irradiated with the Nd:YAG laser) showed 100% demineralization. CONCLUSIONS: These findings are consistent with the finding that laser irradiation of dental results in significant reduction of the effective solubility of enamel mineral. PMID- 11199842 TI - Acute and long-term humoral immunity following active immunization of rabbits with inactivated spores of various Encephalitozoon species. AB - Microsporidia of the genus Encephalitozoon are increasingly being reported as a cause of severe, often disseminated infections, mainly in patients with acquired immunodeficiency syndrome (AIDS). Immunological identification of each of the three recognized species (E. cuniculi, E. hellem, and E. intestinalis) requires the availability of specific immune sera. All sera available thus far have been generated by direct inoculation of rabbits with virulent microsporidian spores. This study demonstrates for the first time that subcutaneous immunization with inactivated spores of E. cuniculi, E. helleri, or E. intestinalis is capable of generating highly active rabbit hyperimmune sera to the homologous antigens, with maximal titers being 1:5,120, 1:1,280, and 1:2,560, respectively, as determined by the indirect immunofluorescence technique (IIF). Broad cross-reactivity of the rabbit antisera with all heterologous Encephalitozoon antigens was determined by IIF and immunogold electron microscopy; however, only the E. hellem immune serum strongly cross-reacted with spores of Enterocytozoon bieneusi. During the 35 month follow-up period the antibody titers to the homologous antigens declined to 1:640, 1:160, and 1:320, respectively. The observed decay curves for antibody titers against E. cuniculi, E. hellem, and E. intestinalis were fitted using mathematical modeling, resulting in a predicted duration for specific immune responses of about 7 years on average. Knowledge of the magnitude and duration of specific immune responses is a prerequisite for further evaluation of the concept of using inactivated microsporidian spores in the quest for vaccines against microsporidian infections. PMID- 11199843 TI - High prevalence of infection with Entamoeba dispar, but not E. histolytica, in captive macaques. AB - A total of 268 nonhuman primates (20 species) kept in the Primate Research Institute, Kyoto University, Japan, were surveyed for intestinal amebas. Total positive rates as based on the presence of cysts in the stool following formalin ether sedimentation were as follows: Entamoeba histolytica/E. dispar, 53%; E. coli, 34%; E. hartmanni, 34%; Iodamoeba buetschlii, 25%; Endolimax nana, 8%; and E. chattoni, 3%. Positive rates were higher in Old World monkeys and lower in New World monkeys. All the 141 E. histolytica/E. dispar-positive animals were Macaca monkeys. The E. histolytica/E. dispar-positive samples were analyzed by polymerase chain reaction (PCR) for identification of E. histolytica and E. dispar. E. dispar DNA was detected in 137 samples, whereas no E. histolytica DNA was seen. Zymodeme analysis and reactivity to monoclonal antibodies of cultured trophozoites also supported the presence of E. dispar and the absence of E. histolytica. When the sera of 93 macaques were examined by an indirect fluorescent antibody test, only 3 animals proved to be positive for E. histolytica, showing the lowest titer. These results demonstrate that infection with E. dispar, but not E. histolytica, is predominant in macaques. PMID- 11199844 TI - Therapeutic and prophylactic effects of isometamidium chloride (Samorin) against the hemoflagellate Cryptobia salmositica in chinook salmon (Oncorhynchus tshawytscha) and the effects of the drug on uninfected rainbow trout (O. mykiss). AB - A series of compounds (triphenylmethanes, thiazines, xanthenes, benzidines, phenanthridiniums, napthalamines, and diamidines) were screened for in vitro toxicity against Cryptobia salmositica. Isometamidium chloride (Samorin) was cryptobiacidal at low concentrations and was examined for therapeutic and prophylactic activities against C. salmositica in chinook salmon (Oncorhynchus tshawytscha). An intramuscular dose (1.0 mg/kg) of Samorin 3 weeks post-infection significantly reduced the parasitemia in adult chinook. A higher dose (2.5 mg/kg) eliminated the infection in 30% of adult fish and parasitemias were significantly reduced in the remaining infected fish. Juvenile chinook treated with 1.0 mg Samorin/kg at 2-3 weeks post-infection survived, while 100% of untreated control fish died from cryptobiosis. The high dose (2.5 mg/kg) was lethal to small fish (98.93 +/- 12.09 g) and 50% died within 24 h of treatment, while all large fish (168.38 +/- 13.87 g) survived. Samorin (1.0 mg/kg) did not affect growth, food consumption, complement, or hematocrit values in uninfected rainbow trout (O. mykiss). PMID- 11199845 TI - Experimental leishmaniasis: synergistic effect of ion channel blockers and interferon-gamma on the clearance of Leishmania major by macrophages. AB - We have previously shown that cultured Leishmania promastigotes are sensitive to drugs blocking K+ and Na+ channels and Na+/H+ transport systems and that the percentage of parasite-infected macrophages decreases significantly in the presence of the drugs. In the present work, we analyzed whether this drug susceptibility of intracellular amastigotes was associated with the activation of macrophage microbicidal mechanisms. Pretreatment of the cells with glibenclamide (GLIB) increased their resistance to infection with Leishmania, an effect that may be mediated by calcium fluxes since it was reversed by ethylene glycol bis (beta-aminoethyl ether)-N,N,N',N-tetraacetic acid (EGTA). It was noteworthy that in infected macrophages post-treated with the drugs the clearance of parasites was strongly enhanced when the cells were treated simultaneously with GLIB and interferon-gamma; this effect correlated with an increased production of reactive nitrogen intermediates. In conclusion, the data suggest that GLIB treatment increases the resistance of macrophages to infection with Leishmania and potentiates the interferon-gamma-stimulated clearance of parasites via the induction of nitric oxide. PMID- 11199846 TI - Experimental infections of copepods and sticklebacks Gasterosteus aculeatus with small ensheathed and large third-stage larvae of Anisakis simplex (Nematoda, Ascaridoidea, Anisakidae). AB - Free-swimming ensheathed larvae of Anisakis simplex were shown experimentally to be ingested by the copepods Oitona similis and Acartia tonsa and by the nauplii of barnacles Balanus sp. The larvae did not grow in the copepod hemocoel. Experimental infections of various malacostracans were unsuccessful. Sticklebacks Gasterosteus aculeatus are naturally infected with larvae of A. simplex in coastal brackish water. Such sticklebacks may have acquired the infection by eating either a crustacean host or third-stage larvae (L3) from fish. Experimental infections of cod Gadus morhua with L3 from viscera of herring Clupea harengus showed that about one-third of the ingested larvae passed through the cod alimentary tract and were extruded whole but dead. Experiments showed that larvae from herring viscera survived and remained infective after at least 6 weeks in brackish water and seawater and that L3 from herring viscera were ingested by sticklebacks (and flounder Platichthys flesus), where they reencapsulated on the viscera; the L3 were alive 2 years later. PMID- 11199847 TI - Comparative studies on the development of Oesophagostomum dentatum in vitro and in vivo. AB - Although in vitro cultivation of Oesophagostomum dentatum provides defined material of third- (L3) and fourth- (L4) stage larvae, these are morphologically and biochemically different from larvae recovered ex vivo. The development of pre cultivated larvae was investigated by rectal transplantation into worm-free pigs with subsequent recovery of worms from intestinal contents after different time periods and determination of worm burdens and sizes. Additionally, the in vitro maintenance of L4 and adults recovered from intestinal contents of orally infected pigs in different media was investigated. Although growth and development rates of cultivated L4 are lower than those of larvae recovered from intestinal contents after oral infection, pre-cultured L4 are able to develop into egg-laying adults in the large intestines (without nodule formation) within 9-14 days in rates comparable with those after oral infection. In contrast, rectally transplanted L3 only establish in low numbers without egg excretion. L4 and adult worms recovered from intestinal contents cannot be maintained in cultivation medium for more than 1 week, although most L4 grow and moult during the first 3 days. Although the standard cultivation conditions for mass production of L4 are not suitable for development or maintenance of preadult and adult stages, L4 recovered from cultures have the ability to establish in vivo as fertile adults, indicating that the basic biological functions are retained in vitro. PMID- 11199848 TI - Efficacy of toltrazuril and ponazuril against experimental Neospora caninum infection in mice. AB - Neosporosis is a disease affecting predominantly fetal development in cattle and dog hosts; and it may cause neuromuscular disfunction in infected newborn calves and pups. Predispositions--including, e.g. transient immunosuppression during pregnancy--may result in an increased dissemination of the parasite within the host or its offspring. Chemotherapeutic treatment of neosporosis may be an issue, provided that an appropriate drug is made available. In this respect, we describe the use of a mouse model for the evaluation of toltrazuril and ponazuril medication as a means of preventing parasite dissemination and subsequent formation of cerebral lesions. Toltrazuril- and ponazuril-treated mice were experimentally infected intraperitoneally (i.p.) with 2 x 10(6) Neospora caninum tachyzoites. The infection was monitored at three levels: clinically, by assessing symptoms, histologically, by assessing the occurrence of cerebral lesions and parasites by immunohistochemistry, and on the molecular level, by detection of parasite DNA using PCR. Chemotherapy using either toltrazuril or ponazuril, both applied in a drinking-water formulation (20 mg toltrazuril or ponazuril kg(-1) body weight day(-1)) completely prevented the formation of cerebral lesions in all treated animals, as assessed by immunohistochemistry. PCR analyses of these treated animals showed that DNA-detectability was reduced by 91% and 90% upon toltrazuril and ponazuril medication, respectively. PMID- 11199849 TI - Entamoeba histolytica: production of nitric oxide and in situ activity of NADPH diaphorase in amebic liver abscess of hamsters. AB - Entamoeba histolytica trophozoites were inoculated into the liver of hamsters and serum nitrate/nitrite levels [expressed as nitric oxide (NO) production] were determined at different times during amebic liver abscess (ALA) development. We also tested the effects of NO synthase (NOS) inhibitors such as N(G)-nitro-L arginine methyl ester (L-NAME), aminoguanidine, and dexamethasone during ALA production. Since NOS activity has been correlated with expression of reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) in tissues, we performed histochemistry studies to determine the activity of the latter in livers infected with E. histolytica trophozoites. Production of NO in serum was directly proportional to the size of ALAs, and NOS inhibitors caused low levels of NO and smaller ALAs. Our data suggest that NO does not have any lytic effect on E. histolytica trophozoites and is therefore incapable of providing protection against the amebic liver infection. In addition, NADPHd activity was detected histochemically in hepatocytes and inflammatory cells associated with focal necrosis containing trophozoites. The positive reactivity observed in these parasites may be attributable to a close biochemical similarity of NADPHd to the NADPH:flavin oxidoreductase described in E. histolytica by other investigators. PMID- 11199850 TI - Molecular arguments for splitting of Schistosoma intercalatum, into two distinct species. AB - The taxonomic status of the two known strains of Schistosoma intercalatum, the Lower Guinea strain (originating from Edea, Cameroon) and the Zaire strain (originating from Kinshasa, Democratic Republic of Congo, formerly Zaire) was examined using random amplified polymorphic DNA (RAPD) markers. Two additional species within the S. haematobium group, S. haematobium and S. mattheei, were included in the study. DNA was extracted from four male and four female worms of each species and strain under investigation. In all, 13 primers gave reproducible and informative marker patterns; the monomorphic bands in all the males and females of each sample were scored, and 138 bands were included in the final analysis. Overall, 14 RAPD fragments were shared by all the schistosomes studied, and 19 RAPD fragments were considered to be sex markers. Only 22% (20/91) of the RAPD fragments were shared between S. intercalatum Zaire and S. intercalatum Cameroon. The mean values recorded for the Nei and Li's genetic distances between S. haematobium and S. mattheei and between S. intercalatum Zaire and S. intercalatum Cameroon were 0.546 and 0.596, respectively. A principal component analysis and one-way analysis of variance (ANOVA/MANOVA) showed a significant separation between S. intercalatum Zaire and S. intercalatum Cameroon. The data support the hypothesis that S. intercalatum Zaire and S. intercalatum Cameroon are distinct species. Additional molecular-biology studies are in progress that involve the use of nuclear and mitochondrial markers to confirm the extent of the genetic divergence prior to the establishment of final decision on the taxonomic status of the two strains of S. intercalatum. PMID- 11199851 TI - Electron microscopic study on sporocysts and sporozoites of parental strains and precocious lines of rabbit coccidia Eimeria intestinalis, E. media and E. magna. AB - The fine structure of sporocysts and sporozoites of parent strains and precocious lines of rabbit coccidia Eimeria intestinalis, E. magna and E. media was studied. The parent strains and precocious lines differ only in the shape and size of refractile bodies (RB). In the sporocysts of precocious lines of E. magna and E. media, one extremely large RB was seen, either inside one of the sporozoites, or free in the sporocyst. In the oocysts of the precocious strain of E. intestinalis, two sporocysts resembled those of the precocious lines of E. magna and E. media, whereas the other two sporocysts did not harbour any RB. Sporozoites of all the precocious lines contained no, or very small, RB after in vitro excystation. PMID- 11199852 TI - Serum levels of vascular cell adhesion molecule 1 in the early post-treatment defervescent phase of falciparum malaria. AB - Elevated plasma or serum levels of vascular cell adhesion molecule 1 (VCAM-1) have been reported in the febrile phase of falciparum malaria. However, little is known about serum VCAM-1 levels in the early post-treatment defervescent phase. Serum VCAM-1, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL 1beta), and creatinine levels were determined in six Japanese patients with uncomplicated falciparum malaria during the acute febrile phase and the early post-treatment defervescent phase. The serum VCAM-1 values recorded for patients during the early post-treatment defervescent phase were significantly lower than those noted during the febrile phase (P < 0.05), but no significant difference in serum creatinine values was identified. TNF-alpha and IL-1beta levels were below the limit of detection in the serum of all patients during both the febrile phase and the early post-treatment defervescent phase. The serum levels of VCAM-1 were not related to parasitemia. PMID- 11199853 TI - Internet user profile in the field of parasitology. AB - This study determined a profile of current Internet users in parasitology, their use patterns on the Internet for parasitologic purposes, and the Web sites they would recommend. In a European survey, 689 parasitologically engaged scientists were asked to fill out a questionnaire about Internet access, current problems, current and future use, and which Web sites they would recommend as well as about the use of e-mail. In all, 153 (22.2%) of the interviewees returned the questionnaire. Only one participant had no access to the Internet. Time expenditure was considered the main problem involved in use of the Internet. The Internet was mainly used for e-mail (96.1%); for literature research (93.5%); for reading of electronic journals (51.6%); and for gathering of information, e.g., about institutes and colleagues (58.2%) and about congresses (49.7%). In the future, 71.9% of the respondents would like to read electronic journals more often and 49.7% would like to use the web more intensively for acquisition of information about congresses, universities, and institutions. Requests for the future included an easier application of the browser software (33%) and a shorter response time (47.7%). The survey demonstrates that the Internet has assumed a definite place in the lives of researchers in the field of parasitology. Survey responses indicate a need for electronic journals. In our opinion, universities and parasitology societies should be urged to publish journals electronically on the Web. To diminish current problems involved in the finding of relevant information on the Internet, we strongly recommend careful reading of the instructions regarding the search engines used. Web pages with clear structures, small file sizes, precise HTML (hypertext markup language) key-word editing, and page titles would facilitate more accurate discovery of specific sites. In addition, there seems to be a need for regular publication of reviewed parasitology-link collections. PMID- 11199854 TI - Genetic immunization with plasmid DNA coding for the ROP2 protein of Toxoplasma gondii. AB - The ROP2 protein of Toxoplasma gondii has previously been proposed as a vaccine candidate against toxoplasmosis. In this work we characterize the immune response induced by injection of plasmid DNA coding for this protein in three strains of mice (BALB/c, C57BL/6, and CBA/J) displaying different levels of susceptibility to toxoplasmosis and compare it with that obtained by vaccination with the live attenuated ts-4 strain of T. gondii. The ROP2 gene was cloned in the eukaryotic expression vector pcDNA3 and the resulting plasmid, named pcDNA3/ROP2, was used to immunize mice. After three immunizations with the plasmid, mice developed antibodies that could be detected by ELISA using a recombinant truncated form of ROP2; and these antibodies also recognized the natural protein by Western blot. Plasmid immunization generated antibodies against the ROP2 of both of the IgG1 and IgG2a isotypes in CBA/J and BALB/c mice and both of the IgG1 and IgG2c isotypes in C57BL/6 mice. However, animals vaccinated with the ts-4 strain generated only IgG2a (in CBA/J and BALB/c mice) or IgG2c (in C57BL/6 mice) against ROP2. Kinetic studies of the generation of isotypes indicated that both isotypes were generated at the same time. Mice immunized with the plasmid DNA did not resist a challenge with the virulent RH strain of T. gondii, while mice vaccinated with the ts-4 strain resisted the same challenge. However, in pcDNA3/ROP2-immunized BALB/c mice, death was significantly delayed with respect to the pcDNA3-immunized control group. These results suggest that plasmid immunization using the ROP2 gene generates a mixed T(H1)/T(H2) response against ROP2, which is different from that obtained by vaccination with live tachyzoites of the ts-4 strain (T(H1) response) and is not protective against the highly virulent RH strain of the parasite. PMID- 11199855 TI - Fasciolopsiasis: is it a controllable food-borne disease? AB - Fasciolopsiasis, endemic to the Orient and Southeast Asia, is a snail transmitted, intestinal, food-borne parasitic zoonosis caused by a trematode, Fasciolopsis buski, which also infects farm pigs. Fasciolopsiasis remains a public health problem despite changes in eating habits, alterations in social and agricultural practices, health education, industrialization, and environmental alterations. The disease occurs focally and is most prevalent in school-age children. In foci of parasite transmission, the prevalence of infection in children ranges from 57% in mainland China to 25% in Taiwan and from 50% in Bangladesh and 60% in India to 10% in Thailand. Control programs implemented for food-borne zoonoses are not fully successful for fasciolopsiasis because of century-old traditions of eating raw aquatic plants and using untreated water. Fasciolopsiasis is aggravated by social and economic factors such as poverty, malnutrition, an explosively growing free-food market, a lack of sufficient food inspection and sanitation, other helminthiases, and declining economic conditions. PMID- 11199856 TI - Helminth fauna of toads in Belorussian Polesie. PMID- 11199857 TI - Helminth fauna of the hare (Lepus europaeus Pallas, 1778) in the southern part of Belarus. AB - Facts about helminth fauna of hares have not been published in Belarus since 1972. Results of helminthological studies of 22 hare carcasses carried out between 1985 and 1999 in the southern part of Belarus are presented. PMID- 11199858 TI - Withdrawal reactions of a premature neonate after maternal use of paroxetine. PMID- 11199859 TI - Guidelines for Group B streptococcus. PMID- 11199860 TI - Neonatal intensive care and parental participation in decision making. PMID- 11199861 TI - [Sensitization to common airborne allergens in school children with bronchial asthma]. AB - The main purpose of the paper was to assess the prevalence of atopy in the population of preadolescent children in Krakow on the basis of allergic skin testing to airborne allergens and to look into the relationship between atopy and chronic asthma-like respiratory symptoms. The field study was carried out in 1998 among 311 children being the subgroup of the cohort of 1044 children included in the 3-year follow-up in Krakow. The health assessment accounted for the standardised interviews and skin prick testing to 11 common airborne allergens. In the total, the positive allergic reaction at least to only one allergen was found in 32.5% children, and it was more prevalent in boys than in girls (40.4% vs 28.1%). Allergy only to indoor allergens was present in 9.7% children, allergy only to outdoor allergens in 9.7%, and allergy both to outdoor and indoor allergens was confirmed in 13% persons. Most frequently, allergy was established to house mites: Dermatophagoides pter. (16.2%), Dermatophagoides farinae (12.0%) and to cat dander (11.4%). Asthma-like symptoms occurred in 11.0% of children and asthma diagnosed by physician in 7.8% of the sample under the study. The results of this study proved that the prevalence of asthma was about twice so high in boys than in girls. The risk of asthma-like symptoms and/or asthma diagnosed by physician increased significantly with the number of positive allergic tests to airborne allergens (OR = 1.30; 95% CI: 1.11-1.52) and atopy in mother (OR = 1.84; 95% CI: 1.03-3.37). PMID- 11199862 TI - [Occupational allergic diseases in the steel industry. Population studies]. AB - The aim of this study was to evaluate the occurrence of occupational allergic diseases of the respiratory system and skin. The study was carried out in a population of 17,600 employees of Huta im. T. Sendzimira (T. Sendzimir Steelworks) in 1992-96. During this period 543 employees were referred to the Occupational Diseases Department with a suspection of occupational allergy. Connection between the kind of occupation and disease was confirmed in 215 cases. 104 (48%) suffered from upper respiratory tract diseases or bronchial asthma and 111 patients (52%) suffered from allergic skin disease as contact dermatitis of the hand or generalized dermatitis. The analysis showed that allergic skin diseases occurred more frequently in 1992-94 and allergenic respiratory diseases were more frequent in 1995-96. Industrial dust containing metals (nickel, chrome, iron, cooper) turned out to be the main allergic factor. The highest prevalence was observed in the Rolling-Mill Department, Chemistry of Coke Department and Incombustible Materials Department. 33% of patients suffering from allergic respiratory diseases and 10% suffering from allergic skin diseases had a family predisposition to allergy (features of atopy). PMID- 11199863 TI - [Concentration of prothrombin fragments 1+2 (F1+2) and thrombin-antithrombin III complexes (TAT)in patients with primary non-small cell lung cancer, before and after resection]. AB - The aim of our study was to detect the hypercoagulability in patients with lung cancer as well as to search for the marker indicating the effectiveness of tumour resection. Twenty four patients aged: 47-66 years were included into the study. The control group comprised 24 healthy human beings. The plasma concentrations of prothrombin 1 + 2 fragments (F1 + 2) and thrombinantithrombin III complexes (TAT) were measured before and 10 days after the tumour resection. It was shown, that F1 + 2 was a more sensitive hypercoagulability marker in patients with NSCLC, than TAT concentrations. Ten days after tumour resections, 78% of the patients have a normal level of TAT, while only 42% showed normalization of F1 + 2 concentrations. Our data indicate on coagulation activation in patients with different histological types of lung cancer. The risk of thromboembolic disorders still remains 10 days after tumour resection. PMID- 11199864 TI - [Evaluation of antianginal efficacy of long-term therapy with low dose isosorbide dinitrate in patients with stable angina pectoris]. AB - The aim of this study was to evaluate two ways of long-term therapy with lower doses of oral isosorbide dinitrate (ISDN) in normal tablets and in sustained release form (SR), in patients with stable angina. METHODS: In double-blind, placebo (PL) controlled with cross-over design study 38 male patients with stable angina and angiographically proven coronary artery disease, received ISDN in normal tablets in two doses: 10 mg and 20 mg, and also two doses SR: 20 mg-SR and 40 mg-SR or PL in the first ingestion and in long-term therapy in two 7 day phases: 4-times-daily (4x) every 6 h and 3-times-daily (3x) with 12 h interval. In 3x patients received ISDN only in doses: 20 mg, 20 mg-SR and 40 mg-SR. After the first ingestion and on the last day of long-term phases, exercise stress tests on the treadmill were performed: preceding ingestion, 2 h and 6 h after. Evaluation of antianginal efficacy of ISDN was performed by analysis of walking times: total, to angina and to ischemia (WTI). RESULTS: 6 h after first ingestion all doses of ISDN improved significantly WTI in comparison to PL: 10 mg by 34.6% (p < 0.01), 20 mg by 49.6% (p < 0.0001), 20 mg-SR by 42.9% (p < 0.001) and 40 mg SR by 52.5% (p < 0.0001). None of the doses improved significantly WTI in the long-term 4x phase, in 3x--only 40 mg-SR by 12.1% (p < 0.05). CONCLUSIONS: Tolerance to anti-anginal efficacy of ISDN in lower doses in long-term therapy 4 times-daily, every 6 h, was found. A 12-h interval is sufficient to prevent tolerance in long-term treatment of sustained-release ISDN in 40 mg dose. Intermitted dosing of nitrates, as a prevention of tolerance, and the practical results of works using other pharmacologic interventions in a clinical setting are discussed in the final section of this paper. PMID- 11199865 TI - [Interaction of platelets with monocytes with regard to arachidonic acid metabolites]. AB - The aim of our study was the assessment whether internal peroxidase of arachidonic acid and/or prostaglandin can be transferred from platelets to monocytes. Monocytes were isolated from whole blood according to the method of Boyum. The monocytes cultures were led in the fluid environment, on the base of RPMI 1640 supplemented with autologous serum. Platelets were isolated from whole blood according to the method of Pinckard. During interaction of monocytes and platelets in the presence of indometacin we ascertained the increased of TXB2 concentrations in supper-natant. Incubation of monocytes in cultures stimulated by LPS in presence of indomethacin with platelets did not cause increased secretion of TXB2. Incubation of platelets with indomethacin in 36 h culture of monocytes stimulated by LPS caused increase concentration of 6-keto-PGF1alfa. The results of our study may suggest the presence of the one way transformation of the arachidonic acid from platelets to monocytes. PMID- 11199866 TI - [Rupture of the cardiac wall during the course of acute myocardial infarction. Personal observations]. AB - Out of 3673 patients with myocardial infarction treated between 1989 and 1998, 128 (54 males and 74 females) deceased due to left ventricle wall rupture (death rate: 18.5%). Thrombolytic therapy started to be used in 1992. It was administered in 36.0% patients with myocardial infarction in the years 1992-1998. Out of the patients deceased due to left ventricle wall rupture thrombolytic was carried out in 24.2%, predominantly in males (31.5%) as compared to females (18.8%). Left ventricle wall rupture during acute myocardial infarction occurred mainly in females (57.7%), in patients with first infarction (89.8%), in the case of anterior wall infarction (66.4%), hypertension (80.5%), in patients aged 61-80 and more (86.7%). Majority of the patients (83.6%) deceased because of this condition between 1 and 7 hospitalisation day, mainly during the first 48 hours (48.4%). PMID- 11199867 TI - [Change of lifestyle as a relevant therapy after myocardial infarction]. AB - The risk of ischemic heart disease is connected with the definite mode of life. Improper nourishment, smoking, alcohol abuse, sedentary lifestyle and excessive mental stress cause disturbances leading to development of atherosclerosis. The change of the lifestyle may prevent from coronary heart disease and may play a main role in secondary prevention, making the prognosis after myocardial infarction much better. The epidemiological and clinical studies have shown the significance of particular risk factors reduction on survival after myocardial infarction and allowed to create the optimal preventive mode of life. Therefore the change of lifestyle should become the priority in the postinfarction therapy. PMID- 11199868 TI - [Physio-pathologic aspects of aging--possible influence of physical training on physical fitness]. AB - Two physiological parameters seem to be of major importance in maintaining physical functioning in the elderly: a capacity to perform aerobic exercises (endurance fitness) and an ability to do anaerobic work, especially maximal muscle force and power. Regular physical activity helps in maintaining these parameters at levels enabling normal functioning at everyday's living, contributing therefore to preservation of functional autonomy and independence in the elderly. PMID- 11199869 TI - [Use of tissue Doppler echocardiography]. AB - Tissue Doppler Echocardiography (TDE) is a new noninvasive technique which shows myocardial tissue by color-mapping. It's based on the color Doppler and used to assess in a direct way left ventricular systolic and diastolic function. It helps to measure velocities, acceleration and energy signal within the myocardial wall. The transmural gradient of velocities can be calculated too. TDE can be used to detect regional systolic dysfunction due to myocardial ischemia and viable myocardium. It gives specific view of intracardiac structures and is useful for identification tumors, thrombus and vegetations. PMID- 11199870 TI - [Asthma caused by allergy to cat fur]. AB - Sensitivity to cats fur alergen, Fel. d. 1 is presented as the second most important cause, after allergy to mites, of perennial atopic asthma. The authors collected the data from literature concerning the concentrations of Fel. d. 1 in homes and public places. Further the structure and production of Fel d. 1 also its cross reactivity and the methods of it's elimination from the environment are described and discussed. Authors own observations of 20 cases of cats fur asthma and atopic dermatitis support the opinion that only half of the patients suspect cats as the cause of their illness and cats fur sensitivity is always accompanied by inhalant or food allergy. PMID- 11199871 TI - [Angioedema is caused by a defect in C1-inhibitor synthesis]. AB - Deficit of the first component of complement inhibitor (C1-inhibitor, C1-inh) may clinically be manifested as angioedema. The disease is characterized by episodic swellings of mucosa and subcutaneous tissue at different locations of the body. Laryngeal swelling can be life-threatening. The major mediators of edema are discussed to be bradykinin and C2b derived peptides. These mediators increase capillary permeability. Antifibrinolytic agents (aminocaproic acid, tranexamic acid) and attenuated androgens (danazol or stanazolol) are used for prophylaxis. Prolonged use both of them might result in more or less severe side effects. In experiments in vitro it has been shown that IFN-gamma, IL-1, IL-6 have a stimulatory effect on C1-inh synthesis. We want to verify the practical use of probiotics as natural inductors of IFN-gamma synthesis for elevating C1-inh level. PMID- 11199872 TI - [Principles of optimal preparation of material from bronchoalveolar lavage (BAL)for cytoimmunologic examinations in interstitial lung diseases ]. AB - In this paper we considered the value of correctly performed bronchoalveolar lavage (BAL) in diagnosis of interstitial lung diseases and in assessment of the activity of pathological process. We indicated the conditions of exact interpretation of the results of BAL cytoimmunological examination, i.e. fine standard handling of BAL material, including its collection, elaboration and choice of lavage site, as well as regarding external (e.g. cigarette smoking) and internal additional factors. We described the influence of BAL fluid recovery and of the method of staining on obtained results. We emphasized routinely performed BAL to be the valuable diagnostic and research tool in pulmonology however, the method may have limited usefulness and unnecessarily burden the patient, if technical guidelines are not observed. PMID- 11199873 TI - [Phenotype of alveolar lymphocytes--theoretical and practical implications]. AB - Actual characteristics of alveolar lymphocytes was presented, including author's own experience, i.e. bronchoalveolar lavage (BAL) lymphocyte typing in over 450 patients with interstitial lung diseases (ILD) and bronchial asthma. In healthy individuals as well as in the patients, alveolar lymphocyte population is dominated by T cell subset. Alveolar T lymphocytes present primed memory cell phenotype and usually do not proliferate; in normal conditions apoptosis occurs very seldom. T cytotoxic cell phenotype is characteristic for CD8 subset. Percent of B and NK cells found in BAL is very low--B cells are localized in interstitial space around the pulmonary alveoli, while NK cells do not seem to play the important role in the local pulmonary defense. CD4/CD8 ratio evaluation in BAL material is an auxiliary tool in ILD diagnostics; it reflects local imbalance between T helper primed memory cells and primed T cytotoxic cells. PMID- 11199874 TI - [Canavan disease in a young infant]. AB - This paper shows the clinical status and neuroimaging data in the youngest described Polish child with Canavan disease. PMID- 11199875 TI - [Allergy to latex]. PMID- 11199876 TI - [Allergy to drugs]. PMID- 11199877 TI - [Contemporary methods in pharmacotherapy in the opiate dependent treatment]. AB - In this review, we present methods of pharmacotherapy in opiate dependence currently used in Poland and worldwide. As problems associated with drug abuse increase in severity, it is particularly important to bring these methods to the attention of medical professionals, governmental agencies and the general public. Here we describe pharmacotherapeutic approaches used in detoxification as well as relapse prevention. The presented methods of detoxification include classical treatments with clonidine and methadone as well as newer methods of rapid and ultrarapid detoxification. Agonists, partial agonists, and antagonists can be used in preventing relapse in detoxified patients. Experimental therapeutic approaches in the treatment of drug dependence are also presented. Psychotherapy and psychiatric care, central to the successful treatment of opiate dependence, are reviewed as well. PMID- 11199878 TI - [Psychoactive agents: an analysis based on cases from the Department of Clinical Toxicology College of Medicine of the Jagiellonian University in Krakow in the years 1997-1999]. AB - The aim of the study was to evaluate the frequency of acute poisoning with psychoactive substances in adult abusers of Krakow population in 1997, 1998 and 1999 and to compare the number of poisoned patients suffering withdrawal syndrome as predominant. 27.2% (n = 945) of all 3472 acute poisonings treated in the Department of Clinical Toxicology in 1997, 36.9% (n = 1193) of all 3236 treated in 1998 and 47.9% (n = 1546) of all 3233 treated cases that were acute poisoning with psychoactive substances among the abusers of Krakow adult population. Ethanol followed by narcotics in 1998, and by drugs coingested with ethanol and by narcotics in 1997 and 1999 was predominant psychoactive agent in all the analysed years. Organic solvents and glue sniffing and drug dependency increased again in 1999. Opiate derivatives produced at home from poppy straw or juice of poppy head were still the most common narcotic detected in body fluids, but decrease in number of acute opiates poisoning was noted in 1999 as compared to previous analysed years. The most of ethanol abusers aged from 30-49 years. The highest incidence of narcotic and drug dependency was noted in age between 20-29 years. PMID- 11199879 TI - [Preliminary evaluation of methadone program in Krakow]. AB - Methadone maintenance programs have effectively reduced opiate dependency and are available in many countries, also in Poland. In Krakow 50 persons were qualified to methadone maintenance treatment. Their age varied from 21 to 46 years, mean 27.8 years. Participants of the programme were mainly educated on basic technical level, unemployed, after 3 to 30 attempts of detoxification treatment. After initial observation at the Detoxification Unit of the Department of Clinical Toxicology and establishing effective daily oral dose of methadone, all patients in Outpatient Clinic of Abuse receive daily adequate dose of methadone, where in parallel, individual and group psychotherapy is used. Methadone programme which was applied seems to prove the fact, that it can significantly improve life quality of addicted patients as well as increase the level of public safety. PMID- 11199881 TI - Nervous regulation of breathing in opiate dependent patient. Part II. Respiratory system efficiency and breathing regulation of persons classified to the methadone maintenance treatment. AB - The measurements of respiratory pattern parameters, occlusion pressure and respiratory tract resistance had never been performed in opiate dependent persons administered by the methadone maintenance treatment. The aim of this study was assessment of ventilatory efficiency and nervous regulation of 35 depended on opiates before starting the treatment. The presently examined opiate addicts classified to the methadone programme had intensified changes in nervous breathing regulation compared to the group of opiate dependent patients treated at the Department of Clinical Toxicology CMUJ in the first stage of controlled abstinence and to the control group. They had the higher values of minute ventilation, occlusion pressure and higher value of tidal volume to the inspiratory flow (VT/TIN) index which is the driving component of the breathing cycle and reflects the activity of the respiratory centres in the spinal cord and pons. A monitoring of respiratory patterns parameters, occlusion pressure and respiratory resistance, which are not disturbed or biased by lack of patient's cooperation, will allow to determinate the direction of changes in ventilatory efficiency in the course of methadone maintenance treatment programme. PMID- 11199880 TI - Nervous regulation of breathing in opiate dependent patient. Part I. Respiratory system efficiency and breathing regulation in the first stage of controlled abstinence. AB - Neurotoxic properties of opioid drugs which are the central nervous system depressant may have also depressive action on the brain stem complex responsible for the breathing control. Disorders of breathing regulation are reflected in respiratory efficiency. The aim of this study was to evaluate the regulation of breathing by measuring of respiratory pattern parameters, occlusion pressure and also to estimate the respiratory efficiency in opiate abusers. There were 76 persons under examination: group I--36 opiates abusers (29 men and 7 women; mean age 22.6 years) treated in the Detoxification Unit of the Department of Clinical Toxicology; group II (control group)--40 healthy persons (25 men and 15 women; mean age 28 years) not dependent of opiates and never treated at the Department. During hospitalisation the functional state of respiratory system was monitored. Ventilation efficiency was determined on the basic of the results from a "flow volume" curve, spirometry and the measurements of the respiratory tract resistance in a computerised system Lungtest-MES company (Poland). Respiratory regulation was evaluated by means of synchronic measurements of the respiratory pattern (according to the assumption of Milic-Emili) and occlusion pressure P 0.1 (according to Whitlaw assumptions). In the examination performed directly after admission to the Unit the normal respiratory efficiency was noted in 24 persons. 12 persons (33.3%) suffered from the bronchi obturation. In the examination performed after hospitalisation and 9 days of total abstinence the normal ventilatory efficiency was found in 23 persons. In 13 of the patients (38.5%) respiratory obturation was still observed. After treatment in group of opiate abusers compared to control group values of respiratory resistance, occlusion pressure, minute ventilation and VT/T(in) index describing the activity of the central breathing regulation were increased, while the time of expiration and time of total breathing cycle were shorter. PMID- 11199882 TI - [Nutritional problems of persons qualified for the methadone treatment. Part I. Nutritional status of opiate addicts]. AB - The aim of the study was assessment of the nutritional status of opiate addicted persons. The study was carried out on 44 opiate abusers (14 women aged from 21-33 years and 30 men aged from 21-46 years), who were classified to methadone maintenance treatment. Nutritional status was assessed by anthropometry methods and body composition was examined using bioelectric impedance. BMI (body mass index) of examined women ranged from 16.4 to 30.8, and BMI of examined men ranged from 17.1 to 44.9. 21% of women and 44% of men had BMI < 15th centile (this indicates undernutrition), 7% of women and 3% of men had BMI > 85th centile (this indicates overnutrition). The medium body fat content for women was 8.7 +/- 6.3 kg (14.7% of body weight), for men 9.5 +/- 8.5 kg (11.9% of body weight). 50% of women and 53% of men had body fat deficiency upper 5% of range adjusted for age and sex, body fat excess upper 5% of range revealed 14% of women and 17% of men. The water content for examined women was 35.5 +/- 6.9 L (62.8 of body weight), for men 47.4 +/- 8.4 L (58.8% of body weight). Water deficiency upper 5% of range revealed 7% of men, 86% of women and 53% of men had water excess upper 5% of range. The lean body mass for women was 48.2% +/- 7.2 kg (85.4% of body weight), for men 62.7 +/- 10 kg (88.4% of body weight). Anthropometry as well as examination of body composition indicate prevalence of energy protein malnutrition among opiate addicted. PMID- 11199883 TI - [Nutrition disorders in persons qualified for the methadone treatment. Part II. Food choice and intake in diets of opiate addicts]. AB - The aim of the study is to establish the composition and nutritional value of daily food in the group of opiate addicted patients qualified to methadone therapy. The presented data show the results of the survey carried out at the start of the treatment in the group of 42 patients (13 women aged from 21-33 years and 29 men aged from 21-46 years). For the dietary survey the method of 24 hour recall was used: nutrients of daily individual diets and mean values with standard deviations for examined groups were calculated with use of own computer programme and polish food composition data. The proportion of energy covered by groups of food products was also calculated. The results show wide distribution of food consumption: the mean level of the daily energy intake was 2438 kcal (SD +/- 976, range 492 kcal to 4193 kcal.) in the group of men, and 2039 kcal (SD +/- 925, range 561-3860 kcal) in the group of women. The mean protein intake was 82 g (13.4 E%) for men and 63 g (12.4 E%) for women. In the diet of 5 men and 6 women carbohydrate energy exceeded 70% of the total energy intake, indicating high consumption of food items containing considerable amounts of sugar (bonbons, confectionery, cakes, sweets, chocolate, sweet drinks and similar). PMID- 11199884 TI - [The evaluation of methods of usage of addictive substances among high school students and Gdansk University students]. AB - Anonymous questionnaire examination was performed among 222 high school pupils and 301 students of Gdansk Medical University, including 210 men and 313 women from 18 to 35 (mean 20.8 +/- 2.56) years old. Marijuana was used by 31.2% of them (once a week or more often 3.82%), amphetamine and Ecstasy by 9.4% (once a week or more often 1.52%), LSD by 3.8%, hallucinogenic mushrooms by 3.1%. Opium alkaloids, peyotl, jimsonweed were taken by a few pupils. The frequency of the drugs usage was significantly higher among school pupils (42.8%) than among Medical University students (30.2%) (chi 2 = 8.80; p < 0.003). Men applied drugs about twice as often as women and the difference was as well statistically significant (chi 2 = 12.95; p < 0.0003). 29.5% men and 25.2% women were cigarette smokers, but only in more advanced smokers (5 cigarettes and more per day) there was a significant difference between male and female (chi 2 = 8.69; p < 0.004). PMID- 11199885 TI - [Poisonings by selected drugs: analysis of 1995-1999 data files of the Clinic of Acute Poisonings Institute of Occupational Medicine in Lodz]. AB - Over the period of 1995-1999 a total number of 439 cases were admitted to the Clinic of Acute Poisonings, Lodz, Poland, due to poisoning with opiates, opioids, amphetamine, cannabis products, LSD and cocaine. Most of the patients were males, the male to female ratio was 1:1.5 (266 to 173). The distribution by age indicated the persons aged 21-30 yr as the highest risk group, then those aged 14 21 yr. Over the period under study the structure of poisonings changed significantly. Since 1997 the number of poisonings with amphetamine and cannabis products increased dramatically, while that of opiate poisonings declined. Approximately 84% of cases were found to be addicted to a combination of drugs and psychotropic agents, mostly benzodiazepine and ethyl alcohol. Drug addiction was reported by over 80% patients with opiate poisoning, 44.8% with tetrahydrocannabinole poisoning and only 9.5% with amphetamine poisoning. The efficacy of treatment in cases of drug addiction is very low. Repeated treatment was reported by almost 100% of patients who had attempted to quit drug abuse. Among opiate poisoning cases, only 8 out of 45 patients did not question the effectiveness of the withdrawal treatment. PMID- 11199886 TI - [Acute ethanol and drug poisoning in alcohol abusers]. AB - In the period from 1997 to 1999 one hundred twenty one alcohol abusers were admitted to the clinic with acute ethanol and drug poisoning, including 95 men and 26 women from 18 to 69 (mean 36) years old. Fifty eight persons were poisoned by ethanol, in remaining 63 cases intoxications were mixed e.g. including benzodiazepines, tricyclic antidepressants, carbamazepine, amphetamine, phenothiazines, barbiturates, theophylline, salicylates. In the mixed poisonings group two men (3.2%) died at the age above 50 years old suffering from congestive heart failure, bronchopneumonia and ventricular fibrillation. In the ethanol intoxication group there was no fatal case. PMID- 11199887 TI - [Fatal ethanol poisoning of the alcohol abusers]. AB - The examined cohort consisted of 137 alcohol abusers, who died suddenly because of the acute ethanol poisoning. Among them there were 109 men and 28 women from 25 to 73 (mean 46.3 +/- 9.22) years old. Autopsy examinations performed in Department of the Forensic Medicine revealed no traumas or diseases explaining the sudden death, but showed the increased blood ethanol concentration from 3.6 to 8.8 (mean 4.67 +/- 0.74) g/l and urine ethanol concentration from 2.0 to 7.3 (mean 4.88 +/- 0.87) g/l. In the period 1996-1999 in Gdansk Province there was twofold decrease in the number of sudden death caused by the acute ethanol poisoning in the alcohol abusers. PMID- 11199888 TI - [Concentration of zinc, copper and magnesium in the serum of drug addicts]. AB - The aim of this study was to determine the concentration of zinc, copper and magnesium in the blood serum of drug addicts in order to ascertain whether drug abuse has an effect on the concentration of these metals. The study was carried out on a group of 33 addicts undergoing treatment at the Department of Clinical Toxicology, Collegium Medicum, Jagiellonian University in Krakow. The control group consisted of 22 young, healthy, drug free, male volunteers. Analyses were performed using flame atomic absorption spectrometry. The results demonstrate that zinc serum concentrations in the examined group of addicts before therapy (mean 0.82 mg/l) were reduced in relation to the control group (mean 1.12 mg/l), and was slightly enhanced after the detoxification process (mean 0.86 mg/l). The opposite effect was observed in the case copper serum concentration. The copper level in the group of addicts on admission to hospital (mean 1.35 mg/l) increased in relation to the control group (mean 1.11 mg/l) and was lower during hospitalisation (mean 1.18 mg/l). The concentration of magnesium in the serum of drug addicts did not change during therapy and was in the same range as in the control group (mean concentrations were 20.3 mg/l, 20.2 mg/l and 20.6 mg/l respectively). PMID- 11199889 TI - [Profile of chemical analyses of psychoactive substances in the Laboratory of the Department of Clinical Toxicology in the years 1990-1999]. AB - The chemical-toxicological Laboratory of the Department of Clinical Toxicology carry on the analyses of xenobiotics in biological fluid collected from poisoned patient leaving in Krakow and south-eastern Poland. The evaluation of frequency of performed analyses in the years 1990-1999 shown that among psychoactive substances, ethanol is the most common reason of acute poisoning, followed by psychotropic drugs and drugs of abuse. The level of ethyl alcohol above 2 g/L was observed in more than 40% of patients. In evaluated period the number of barbiturates analyses dropped, benzodiazepines stayed on the same level. During this time evident increase of illicit drugs (amphetamines, opiates and THC) analyses was observed. PMID- 11199890 TI - [Comparison of identification methods of compounds from the opium alkaloids groups on Remedi HS instrument with immunoassay methods]. AB - The biological material of 28 abusers of compounds from the group of opium alkaloids were toxicologically analysed. To preliminary estimation of psychoactive substances ingestion the immunoassay methods (EMIT or FPIA) were used. The received results of total estimation compounds from opium alkaloids and their metabolites were compared to the ones obtained from high-performance liquid chromatography identification method with using Remedi HS. In the evaluated materials of all patients morphine, codeine, N-desmethylcodeine were identified. The presence of 6-mono-acethylmorphine was found in the urine of only 4 patients, which indicates the instability and a little amount of heroine in "kompot" of domestic production. The identification method can be used for simultaneous estimation of other substances of abuse from the groups of amphetamines and phenothiazines. PMID- 11199891 TI - [Medico-legal certification of fatal cases after drug: abuse in the light of modern toxicological analysis]. AB - Introduction of modern instrumental methods for toxicological analysis make possible a detection and identification of xenobiotics in different kind of multicomponents biological samples (plant sources of narcotics, body fluids and tissues of abusers) on a low concentration level. In this way a range of possibilities for the interpretation of toxicological results was enlarged. General medicolegal trends are strictly connected with modern analytics and they can be discussed on the basis of drug--users and fatal cases of intoxications with narcotics. Toxicological findings of these cases were worked out by means of modern analytical method--liquid chromatography with mass detection (LC/MS). PMID- 11199892 TI - [Self-poisoning with Datura stramonium]. AB - During last 5 years only single cases of poisoning with plants containing psychoactive substances, especially Datura stramonium, were treated in the Department of Clinical Toxicology in Krakow. In autumn 1999, during 1 month, 7 patients, aged from 14 to 27 years (mean 18 years) poisoned with Datura stramonium were treated. On admission in all patients central and peripheral anticholinergic symptoms were stated. Four of them ingested seeds, three of them chewed seeds and leaves. Only one ingested Datura seeds in suicidal attempts. In the group, only one--20-years-old--previously abused amphetamine and smoked marihuana. For the remaining 5 boys (14-18 years-old), it was the first experience with psychoactive substances. All were successfully treated, in 5 patients physostigmine was used, in dose ranged from 2 to 6 mg, with no adverse effects. Seasonal accessibility of natural psychoactive products may be the first, easy, free step of addiction. PMID- 11199893 TI - [Self-poisonings of the addicted persons with corrosive substances]. AB - In this paper we present two cases of suicidal behaviour; case (1)--patient dependent to medicines and case (2)--patient co-dependent, related with alcohol addicted person. Both of them combine suicidal corrosive substances consumption, but differ clinical course, finished by recover of addicted person and death of co-dependent person. In this paper we also present chemical burns of gastrointestinal tract algorithm procedure. PMID- 11199894 TI - [Intravenous self-administration of metallic mercury by two alcohol abusers]. AB - This paper presents two alcohol abusers, who intravenously self-injected metallic mercury. In one of them during the injection a portion of mercury penetrated into extravenous compartment of his right arm. The second patient with depression, sociopathy and three suicide attempts in the past repeated intravenous injections with small amounts of mercury several times. The results of physical examination and all laboratory tests for both the men were normal. Blood mercury concentrations were 300 micrograms/l and 710 micrograms/l, respectively. X-ray film revealed the presence of metallic mercury deposits in lungs, right ventricle and inside the interstitial tissue of the right arm. The largest deposits of mercury inside and necrotic tissue were surgically removed from the right arm. PMID- 11199895 TI - [How to differentiate acute isopropanol poisoning from ethanol intoxication? -- a case report]. AB - 18-year-old man was found at the street in an unconsious state and brought to Department of Acute Poisonings with suspicion of unknown xenobiotic ingestion. There was no reliable informations concerning poisoning circumstances. On admission patient was confused and unable to answer questions; physical examination revealed symptoms resembling ethanol intoxication. Results of laboratory tests (e.g., ketonemia and lack of abnormalities of gasometric parameters; ethanol, methanol and ethylene glycol in blood and urine were absent) enabled to presume acute poisoning with isopropyl alcohol. According to informations obtained from patient's parents he had drunk unknown amount of liquid using as printing machine cleaner. During next hours rising acetone concentration in blood (1.7 g/l--4 hours after admission, 2.4 g/l--12 hours after admission) and ketonuria were observed. There was no possibility to evaluate level of isopropanol in blood and urine up to 12 hours after admission--gas chromatography performed at that time revealed lack of isopropanol both in blood and urine. Liquid brought by patient's parents was identified (on gas chromatography) as isopropyl alcohol. Patient was directed to be treated on hemodialysis, because of high concentration acetone in blood. After 16 hours- long hemodialysis patient came back to Department of Acute Poisonings. 3 days later patient left hospital in good condition. PMID- 11199896 TI - [Homocysteine as a risk factor for atherosclerosis]. AB - This article presents current views on the significance of homocysteine as a potential risk factor for atherosclerosis. The majority of numerous and extensive comparative examinations indicate that considerable hyperhomocysteinemia is an independent risk factor for the development of the premature atherosclerotic lesions. Because of that experts of the Nutrition Committee of American Heart Association published in 1999 the recommendations for the application of the preventive diet rich in vitamins B6, B12 and folic acid. PMID- 11199897 TI - [Viper bites]. AB - The common European adder (Vipera berus) is the only naturally occurring venomous snake in Poland. Adder bites occur mainly in the summer usually to individuals who accidentally or purposely bother snakes. Children often become victims of adders. The most common symptoms are: local swelling, rash and discoloration around the bite. General symptoms such as extensive edema spreading to the trunk, vomiting and diarrhoea, acute renal failure, CNS disturbances and cardiovascular problems are not frequent. Haemorrhages are extremely rare. Shock, although also rare, is the most serious symptom. Fatalities are quite exceptional. The treatment should start first of all with immobilization of the bitten limb and in most cases it will suffice. Any patient suspected of being bitten, should be kept under observation in hospital, where the supportive care is possible, if needed. Antivenoms, thought quite safe nowadays, can be used in case of adults only when all of the other means including intensive shock care have been ineffective. In children early treatment with new more purified antivenoms may be considered however existing literature does not offer evidence based efficiency of such treatment in larger groups of children. Tetanus protection is a routine. PMID- 11199898 TI - [ECG disorders in the course of acute suicidal poisonings by verapamil]. AB - Data based on experience of Regional Toxicological Centre in Poznan shown that most of patients self-poisoned with calcium channel blockers were cases of verapamil overdose (41 among 50 patients treated during years 1994-1999). Verapamil's greatest toxic effect is on the conduction system, with depression of the sinus node and of conduction through the atrioventricular node, but it also causes severe myocardial depression. Sings of verapamil toxicity are: sinus bradycardia, sinus arrest, narrow complex junctional bradycadia, varying degrees of AV block, acute congestive failure and cardiogenic shock, hypotonia. In this paper 4 cases with ECG disturbances in the course of verapamil intoxication are presented. PMID- 11199899 TI - Current world literature. Bibliography. PMID- 11199900 TI - Comparison of mitral valve prolapse in dogs and humans. PMID- 11199901 TI - The good doctor: the literature and medicine of Anton Chekhov (and others). PMID- 11199902 TI - Family medicine scholars: a longitudinal enrichment program for medical students. PMID- 11199903 TI - Media advocacy for the office-based teacher of family medicine. PMID- 11199904 TI - Reflections on precepting. PMID- 11199905 TI - Continuity of care and trust in one's physician: evidence from primary care in the United States and the United Kingdom. AB - BACKGROUND AND OBJECTIVES: Patients' trust in their physician to act in their best interest contributes to the effectiveness of medical care and may be related to the structure of the health care system. This study explored the relationship between continuity of care and trust in one's physician, particularly in terms of differences between the United States and the United Kingdom (UK). METHODS: We conducted a cross-sectional survey of adult patients (n = 418 in the United States and n = 650 in the UK) who presented in outpatient primary care settings in the United States (Charleston, SC, and Lexington, Ky) and in the UK (Leicester and Exeter). RESULTS: A high percentage of both groups of patients reported having a usual place of care and doctor. A total of 69.8% of UK patients and 8.0% of US patients have had their regular physician for > or = 6 years. US patients (92.4%) are more likely than UK patients (70.8%) to value continuity with a doctor. Both groups had high levels of trust in their regular doctor. Trust was related to one continuity measure (length of time for the relationship) but not to another (usual provider continuity index more than 1 year). In a multivariate model, country of residence had no independent relationship with trust, but continuity of care was significantly related. CONCLUSIONS: Higher continuity is associated with a higher level of trust between a patient and a physician. Efforts to improve the relationship between patients and physicians may improve the quality and outcomes of care. PMID- 11199906 TI - A national survey of procedural skill requirements in family practice residency programs. AB - BACKGROUND AND OBJECTIVES: Procedural skill training is a controversial but important component of family practice residency programs. This study examines the use and composition of required procedure lists in US family practice residency programs. METHODS: The study used a cross-sectional nine-item questionnaire. This survey was sent to 467 residency program directors listed in the 1999 American Academy of Family Physicians Directory of Family Practice Residency Programs. RESULTS: A total of 326 programs (70%) responded to the survey. Of these, 242 programs (74% of respondents) reported use of a required procedure list. Sixty-six programs provided a list. Of these, 63 lists were interpretable. The number of required procedures on the lists ranged from a minimum of 3 procedures to a maximum of 117, with an average of 42. A total of 265 distinct procedures were identified, with 25 procedures named on more than half of the lists. Thirteen programs (21%) mandated competency in required procedures, but only five programs (8%) gave clear definitions of what constituted competency. There were no significant differences in lists among training program type, university affiliation, number of hospitals used for rotation, size of affiliated hospital, or number of residents. CONCLUSIONS: The expectations of individual programs vary greatly in terms of required procedures. Few programs define how to evaluate the technical competency of their residents. PMID- 11199907 TI - Teaching cardiac auscultation using simulated heart sounds and small-group discussion. AB - BACKGROUND AND OBJECTIVES: Several educators have reported poor identification of abnormal cardiac sounds by primary care residents. Practice and review with cardiology patient simulators and prerecorded heart sounds has been shown to increase the accuracy of diagnosis by medical students and residents. METHODS: The participants were 15 members of an urban family practice residency. The residents were presented with simulated heart sounds and were asked to identify them in a pretest and posttest. Between the tests, participants were invited to three separate teaching sessions that involved a discussion of cardiac auscultatory findings and a review of audiotaped similar heart sounds. Residents who were unable to attend the teaching sessions formed a control group. RESULTS: The pretest identification rate was 36% for the heart sounds. This improved to 62% for all residents after the intervention. Higher rates of improvement were demonstrated by the residents who attended one or more teaching sessions, compared with the residents who attended no teaching sessions. CONCLUSIONS: Small group discussion and repetitive auscultation of simulated heart sounds can improve the cardiac auscultatory proficiency of family practice residents. PMID- 11199908 TI - Successful Duluth program narrows the gender gap. PMID- 11199909 TI - Medical student body weight and preclinical medical education. PMID- 11199910 TI - [HIV protease inhibitors. Development and overview] . PMID- 11199911 TI - ["It is necessary, so we go here." Drug development in the in DDR particularly antihistamines] . PMID- 11199912 TI - [Fomocaine from the chemical, pharmacokinetic and pharmacologic viewpoint: current status and overview]. PMID- 11199913 TI - [In vitro methods for the study of phase I metabolism] . PMID- 11199914 TI - [Neuroactive steroids: actions and risks] . PMID- 11199915 TI - [Plant excipients--valuable pharmaceutical aids or superfluous ballast?] . PMID- 11199916 TI - [Inhibitors of histone deacetylase as new agents for prevention and treatment of cancer] . PMID- 11199917 TI - Mycophenolate mofetil in lupus nephritis. PMID- 11199918 TI - From BILAG to BLIPS--disease activity assessment in lupus past, present and future. AB - During the past 16 years, members of the British Isles Lupus Assessment Group (BILAG) have met on a regular basis and have been instrumental in devising a comprehensive disease activity index and, in association with others in the international rheumatological community, devising and/or testing damage and patients self-assessment indices. The history of what the BILAG group has achieved is set out here and the latest attempts at computerisation and improvements in the Disease Activity Index itself are described. PMID- 11199919 TI - Immunization with a bacterial ATP-binding cassette transporter fragment suppresses autoimmunity and prolongs survival in MRL/lpr lupus-prone mice. AB - The present study was undertaken to better define the role of the U1 70 kDa antigen in a spontaneous murine model of systemic lupus erythematosus (SLE) by testing whether immunization with the U1 70 kDa polypeptide could alter the production of antibodies against U1 70 kDa or against other small nuclear ribonucleoproteins (snRNP), modify disease expression or alter survival. We found that, while immunization with a U1 70 kDa derived fusion protein (70 KFP) tended to delay the development of anti-snRNP antibodies in the sera of MRL/lpr mice, it had no effect on autoimmune-mediated renal disease or survival. Unexpectedly, it was found that MRL/lpr mice immunized with a 367 amino acid fragment of a bacterial ATP-binding cassette transporter, MFP, had prolonged survival compared to saline injection or U1 70 kDa immunization and that this was associated with a delay in the onset of SLE-like proliferative glomerulonephritis. This is the first study, to our knowledge, in which a bacterial ATP-binding cassette transporter was shown to be beneficial in treating a murine model of SLE. We report that MFP significantly prolonged longevity in the MRL/lpr murine model of SLE compared to saline injection or 70 KFP immunization and that improved survival was associated with a delay in the onset of SLE-like glomerulonephritis. PMID- 11199920 TI - Activation of type I interferon system in systemic lupus erythematosus correlates with disease activity but not with antiretroviral antibodies. AB - The objective was to investigate the relation between serum levels of interferon alpha (IFN-alpha), the activity of an endogenous IFN-alpha inducing factor (SLE IIF), clinical and immunological disease activity as well as serum levels of antiretroviral antibodies in SLE. Serum levels of IFN-alpha were measured in serial sera from 30 patients sampled at different stages of disease activity (SLEDAI score). The SLE-IIF activity was measured by its ability to induce IFN alpha production in cultures of normal peripheral blood mononuclear cells. Both serum IFN-alpha and SLE-IIF increased markedly at flare in serially followed patients. The SLEDAI score, levels of anti-dsDNA antibodies and IL-10 correlated positively, and complement components Clq, C3 and leukocytes correlated inversely with serum concentrations of IFN-alpha. The extent of multiple organ involvement correlated with serum IFN-alpha. No relation between concentrations of retroviral peptide binding antibodies and IFN-alpha or SLE-IIF activity was found. The close relationship between disease activity in SLE patients and IFN-alpha serum levels suggests that activation of the type 1 IFN system might be of importance in the disease process. PMID- 11199921 TI - Vascular events in hypertensive patients with systemic lupus erythematosus. AB - Our purpose was to examine prospectively the relationship between systemic hypertension and vascular events in patients with SLE. SLE patients followed in the University of Toronto Lupus Clinic presenting between 1980 and 1988 and within one year of their diagnosis of SLE were identified. Standard definitions were used for hypertension and for all vascular events (MI, angina, CVA, PVD). The presence of traditional CAD risk factors, along with disease- and therapy related risk factors for the development of vascular disease, were compared in the hypertensive and normotensive group. A multivariate logistic regression was performed to determine the best predictor of a vascular event. One hundred and fifty patients were identified in our inception cohort [75 hypertensive (50%) and 75 (50%) normotensive]. Seventeen hypertensive patients (22.7%) had at least one vascular event as compared to six (8.0%) normotensive patients (p = 0.022). The vascular events included 7 with CAD, 5 with CVA, and 5 with PVD in the hypertensive group while in the normotensive group 3 patients developed CAD, 2 CVA and 1 PVD. Fifteen deaths were recorded in the hypertensive group as compared to eight deaths in the non-hypertensive groups (P = 0.09). The groups were comparable with respect to associated risk factors, except for higher frequency of hypercholesterolemia (P = 0.003), azotemia (P = 0.001) and corticosteroid use (P = 0.038) in the hypertension group. In a multivariate analysis the best predictor of a vascular event was hypercholesterolemia (OR 6.9, 95% CI 2.4-24.8, P < 0.001). We conclude that systemic hypertension is associated with an increased frequency of vascular events in SLE. This is best explained by its association with hypercholesterolemia. PMID- 11199922 TI - Safety profile and causes of withdrawal due to adverse events in systemic lupus erythematosus patients treated long-term with cyclosporine A. AB - Several case reports and uncontrolled trials have established the use of cyclosporine A (CsA) in systemic lupus erythematosus (SLE) but some concerns have been raised because of its kidney damaging effects. We here report the results of a retrospective follow-up study designed to assess the safety profile and causes of discontinuation due to adverse events in SLE patients treated with CsA. We treated 56 SLE patients with oral CsA at doses of 3-5 mg/kg for an average of 26 months. Adverse events not leading to the discontinuation of therapy were observed in 62.5% of the patients, the most frequent being hypertrichosis. CsA was stopped because of the occurrence of side effects in 9/56 (16%) of the patients. The most common were nephrotoxicity (3/9) and the occurrence of tremors (3/9). These effects were always reversible within three months of CsA withdrawal. The patients who were older than 40 y had a significant slightly increased risk of stopping CsA therapy for any adverse events (RR 1.08; CI 95% 1.03-1.14). In comparison with previous studies, this study involved a larger cohort of SLE patients who were evaluated for a longer period of follow-up, and confirmed the good tolerability of CsA in these subjects. PMID- 11199923 TI - ASE-1: an autoantigen in systemic lupus erythematosus. AB - ASE-1 is a 55 kDa nucleolar autoantigen. We show that autoantibodies to this antigen occur at a higher frequency in the sera of patients with SLE than in other systemic rheumatic diseases and that the specificity of ASE-1 as a serum marker of SLE increases as the number of epitopes recognized by the sera increases. Autoantibodies to ASE-1 were temporally associated with autoantibodies to HsEg5 but were not found in conjunction with other known serum markers of SLE. The frequency of antibodies to ASE-1 epitopes in a SLE cohort was approximately the same as anti-dsDNA. However, anti-dsDNA is associated with renal involvement, whereas ASE-1 reactivity shows an association with a history of serositis. We conclude that ASE-1 is correlated with serositis and that ASE-1 should be added to a list of autoantigens that are considered important serological features of SLE. PMID- 11199925 TI - The rating scale preference measure as an evaluative measure in systemic lupus erythematosus. AB - Preference measures may be useful tools to assess patients' overall health related quality of life. We studied the validity and sensitivity to change of the rating scale preference measure in patients with systemic lupus erythematosus (SLE), and compared its properties with those of the patient global assessment of SLE activity, in a prospective longitudinal observational study of changes in the symptoms and clinical disease activity of 23 patients. Patients were assessed every two weeks for up to 40 weeks. Construct validity was assessed by the strength of correlations between changes over time in the rating scale preference measure and patient global assessment and changes in the physician global assessment, Systemic Lupus Activity Measure (SLAM), European Consensus Lupus Activity Measure (ECLAM), the British Isles Lupus Assessment Group index (BILAG), and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Changes in the rating scale were more highly correlated with changes in each of these standards than were changes in the patient global assessment, demonstrating the construct validity of this measure. Sensitivity to change was measured using the two-week interval of greatest change in either the physician global assessment or the SLE activity measures as standards. The rating scale preference measure was less sensitive to change than the patient global assessment when tested against four different standards. The sensitivity to change of the rating scale was less than one-half that of the patient global assessment when either the SLAM or ECLAM was used as the standard. Although these results support the validity of the rating scale as a measure of health-related quality of life in patients with SLE, its limited sensitivity to change may make it less attractive as an endpoint measure in clinical trials. PMID- 11199924 TI - Antioxidant susceptibility of pathogenic pathways in subjects with antiphospholipid antibodies: a pilot study. AB - The pathogenesis of antiphospholipid antibody (aPL) related thrombosis is multifactorial and includes, amongst others, enhanced coagulation activation measured as prothrombin fragment 1 + 2 (F1 + 2), elevated plasma levels of von Willebrand factor (vWF), plasminogen activator inhibitor (PAI) and endothelin-1 (ET-1) as well as heightened thromboxane generation and lipid peroxidation. To evaluate the antioxidant susceptibility of some of the above pathways, probucol (500 mg/d orally, a cholesterol lowering agent bearing antioxidant properties) was administered for a three week period to 14 subjects with aPL and to seven healthy controls. At baseline aPL participants showed higher plasma levels of vWF (P = 0.006), ET-1 (P = 0.0002) and enhanced urinary excretion of 11-dehydro thromboxane-B2 (TXB2) (P = 0.0004), F2-isoprostanes (marker of lipid peroxidation) (P = 0.02) and albumin (P = 0.04) than controls. In the aPL group baseline IgG anticardiolipin (aCL) titre positively related with urinary TXB2 (r2 = 0.43, P = 0.01) and inversely with urinary NOx (r2 = -0.6, P = 0.005) whereas urinary NOx and TXB2 were negatively correlated (r2 = -0.42, P = 0.01). After the treatment period significant decreases from baseline values were noted for PAI (P = 0.01), ET-1 (P = 0.006), TXB2 (P = 0.02), F2-isoprostanes (P = 0.01) and albuminuria (P = 0.01) in aPL participants but not in controls. These pilot data support oxidative sensitive mechanisms and a potential role for antioxidant treatment in the pathogenesis of aPL induced vasculopathy. PMID- 11199926 TI - Validation of a Chinese version of the Medical Outcomes Study Family and Marital Functioning Measures in patients with SLE. AB - The objective was to validate a Chinese translation of the Medical Outcomes Study Family and Marital Functioning Measures (FFM and MFM) in patients with systemic lupus erythematosus (SLE). Chinese-speaking SLE patients (n = 69) completed a self-administered questionnaire containing the FFM and MFM and assessing demographic and socio-economic status twice within a 2 week period. SLE activity, disease-related damage and quality of life were assessed using the BILAG, SLICC/ACR Damage Index and SF-36 Health Survey, respectively. Scale psychometric properties were assessed through factor analysis, Cronbach's alpha, quantifying test-retest differences and known-groups construct validity. Factor analysis identified 1 factor corresponding to the FFM and 2 factors corresponding to the MFM. Internal consistency for the FFM was excellent (alpha = 0.92) while that for the MFM was acceptable (alpha = 0.62). Mean (s.d.) test-retest differences were 0.06 (1.54) points for the FFM and 0.03 (2.08) points for the MFM. 11 and 10 of 13 a priori hypotheses relating the FFM and MFM, respectively, to demographic, disease and quality of life variables were confirmed, supporting the construct validity of these scales. The Chinese FFM and MFM are valid and reliable measures of family and marital functioning in Chinese-speaking SLE patients, with psychometric properties very similar to the source English version. PMID- 11199927 TI - Validation of the Chinese SF-36 for quality of life assessment in patients with systemic lupus erythematosus. AB - We studied the reliability and validity of the Chinese Short-Form 36 Health Survey (SF-36) in a cross sectional study of patients with systemic lupus erythematosus (SLE). Sixty-nine consecutive subjects completed a questionnaire containing the Chinese SF-36 twice within 14 d. Disease activity and damage were assessed using the British Isles Lupus Activity Group (BILAG) and SLICC/ACR Damage Index (DI) scales, respectively. Internal consistency was assessed using Cronbach's alpha, reliability using Spearman's correlation and repeatability coefficients, and relationships between SF-36, BILAG and DI scores using Spearman's correlation. The Chinese SF-36 showed high internal consistency (alpha = 0.72-0.91) and good reliability, with correlations exceeding 0.70 for 7 scales and mean scale score differences of < 2 points for 6 scales. SF-36 scores correlated weakly with BILAG scores (-0.27 to -0.41) and DI scores (-0.24 to 0.35), and subjects' mean SF-36 scores were 6-24 points lower than the general population, supporting construct validity of the SP-36. These data suggest that the Chinese SF-36 is a reliable and valid measure of quality of life in patients with SLE. PMID- 11199928 TI - Maculopapular lupus rash in a young woman with systemic involvement. AB - We describe a 23-y-old woman with known systemic lupus erythematosus (SLE) who presented to us with the characteristic maculopapular lupus rash. Although well known among the LE-specific skin lesions, this acute cutaneous manifestation is rarely reported. PMID- 11199929 TI - Wegener's granulomatosis associated with antiphospholipid syndrome. AB - We report a case of Wegener's granulomatosis (WG) with pulmonary hemorrhage also satisfying the criteria for antiphospholipid antibody syndrome (APS). This association has, to the best of our knowledge, never been described before. Pulmonary hemorrhage may be an early manifestation of several immune and idiopathic disorders such as ANCA-associated vasculitis. Several case-reports of APS patients with capillaritis have been described. A possible explanation is that microvascular thrombosis with subsequent increase in vascular permeability facilitates perivascular IgG and complement deposition leading to development of capillaritis. Whether the vascular disease is secondary to thrombosis or vasculitis or both is important in choosing the proper management strategy. We suggest that anticardiolipin antibodies (aCL) should be detected in ANCA associated vascularitis because they may contribute to life-threatening events superimposed on vascular damage. PMID- 11199930 TI - SLE, diabetes mellitus and emphysematous infections of the urinary tract. PMID- 11199931 TI - Drug transporters revisited. PMID- 11199932 TI - Panic disorder and response to sertraline: the effect of previous treatment with benzodiazepines. AB - More than 50% of patients who seek psychiatric care for panic disorder have previously received prescriptions for a benzodiazepine (BZ). Research on the treatment of generalized anxiety suggests that a history of BZ exposure might decrease the efficacy and tolerability of treatment with a serotonergic anxiolytic. This study examines the effect of prior BZ treatment on the efficacy and tolerability of sertraline treatment for panic disorder. Data were pooled (N = 705) from four double-blind, placebo-controlled studies of the efficacy of sertraline for the treatment of panic. Two of the studies were 12-week fixed-dose studies with starting doses of 50 mg, whereas 2 were flexible-dose studies of 10 week duration with starting doses of 25 mg. The effect of study treatment on the frequency of panic attacks, Clinical Global Impressions (CGI) Improvement Scale, and tolerability was examined for patients with or without prior BZ treatment. The efficacy of sertraline was not affected by prior treatment with BZs. The mean endpoint reduction in panic attack frequency was identical in patients with or without prior BZ use: 79% vs. 80% (not significant). A history of good versus poor response to prior BZ treatment did not significantly influence CGI responder rates for sertraline-treated patients (67% vs. 61%, respectively). Sertraline CGI responder rates were significantly greater than placebo response, which was 47% for the good-response prior-BZ subgroup (p = 0.007), and 36% for the poor response BZ subgroup (p = 0.013). Placebo response was lower in patients with any prior BZ use by 10% on an intent-to-treat last-observation-carried-forward analysis (p = 0.106) and by 15% on a completer analysis (p = 0.045). Prior BZ use did not influence either rates of adverse events or discontinuation rates within the first 3 weeks in patients treated with either sertraline or placebo. Sertraline is both well-tolerated and has significant efficacy in patients with panic disorder, including the subset of patients with panic disorder who have previously been treated with BZs. PMID- 11199933 TI - Adverse drug interaction between risperidone and carbamazepine in a patient with chronic schizophrenia and deficient CYP2D6 activity. PMID- 11199934 TI - Atypical antipsychotics and cardiovascular risk in schizophrenic patients. PMID- 11199935 TI - Heroin and schizophrenia: subjective responses to abused drugs in dually diagnosed patients. PMID- 11199936 TI - Repeated episodes of hypothermia in a subject treated with haloperidol, levomepromazine, olanzapine, and thioridazine. PMID- 11199937 TI - A case of risperidone-induced stuttering. PMID- 11199938 TI - Venlafaxine treatment of patients with comorbid alcohol/cocaine abuse and attention-deficit/hyperactivity disorder: a pilot study. PMID- 11199939 TI - Successful treatment of nonanticholinergic delirium with a cholinesterase inhibitor. PMID- 11199940 TI - The economic consequences of a drug-drug interaction. PMID- 11199941 TI - Treating neuroleptic malignant syndrome as catatonia. PMID- 11199942 TI - Olanzapine plasma concentrations and clinical response: acute phase results of the North American Olanzapine Trial. AB - Olanzapine is an atypical antipsychotic that is effective in the treatment of schizophrenia. Olanzapine plasma concentrations > or = 9.3 ng/mL (24 hours postdose) have been identified as a predictor of clinical response in acutely ill patients with schizophrenia. The authors report a receiver operating characteristic (ROC) curve analysis of 12-hour olanzapine concentrations and treatment response from the North American Double-Blind Olanzapine Trial. After a 4- to 7-day placebo lead-in, patients meeting DSM-III-R criteria for schizophrenia were randomly assigned to receive olanzapine, haloperidol, or placebo. Patients who were randomly assigned to receive olanzapine were given daily doses ranging from 2.5 to 17.5 mg/day for up to 6 weeks. Blood samples for the determination of olanzapine plasma concentrations were obtained between 10 and 16 hours (11.7 +/- 1.7 hours) after the last dose was administered. Therapeutic response data and olanzapine concentrations used for analysis were obtained from the endpoint visit for each patient if the patient had been receiving a fixed olanzapine dose for at least the last 2 weeks of the study. Plasma concentrations from previous visits were used if endpoint concentrations were invalid. Response was defined as a > or = 20% reduction in Brief Psychiatric Rating Scale (BPRS) scores and a Clinical Global Impression (CGI) Severity scale score of < or = 3 or a final BPRS score of < or = 35. The final ROC analysis included data from 84 patients and suggested an olanzapine concentration > or = 23.2 ng/mL to be a predictor of therapeutic response. Fifty-two percent of patients with 12-hour olanzapine concentrations > or = 23.2 ng/mL responded, whereas only 25% of patients with concentrations < 23.2 ng/mL responded. Furthermore, an olanzapine concentration > or = 23.2 ng/mL was a predictor of response in the Scale for the Assessment of Negative Symptoms (> or = 20% decrease and endpoint CGI < or = 3). Olanzapine concentrations were found to be a function of olanzapine dose (in milligrams per day) and gender such that prospective olanzapine dosing is feasible. A 12-hour olanzapine plasma concentration of > 23.2 ng/mL was a predictor of therapeutic response in acutely ill patients with schizophrenia. Males required a higher olanzapine dose to reach this threshold concentration than their female counterparts. PMID- 11199943 TI - Divalproex sodium augmentation of haloperidol in hospitalized patients with schizophrenia: clinical and economic implications. AB - Divalproex sodium has been approved for use in treating bipolar disorder. Its usefulness in schizophrenia has yet to be adequately assessed. Three days after initiating haloperidol treatment, patients who were hospitalized for an acute exacerbation of schizophrenia received either valproate augmentation (early augmentation group) or continued to receive haloperidol alone (no-augmentation group). Patients in the no-augmentation group who failed to respond 14 days after the dose of haloperidol reached 20 mg/day received valproate augmentation (delayed-augmentation group). By day 14, the early-augmentation group improved 32.4% more than the no-augmentation group. Fifty percent of the patients in the no-augmentation group failed to respond to haloperidol alone for 2 weeks. They improved by 29% upon the addition of valproate. Compared with those who received no or delayed augmentation, the early-augmentation group required 44.8% fewer inpatient days from the initiation of haloperidol treatment. Patient response to treatment was particularly noted in suspiciousness, hallucinations, unusual thought content, and emotional withdrawal. Early augmentation with valproate may reduce the length of inpatient stays and provide substantially better therapeutic outcomes. It is, however, premature to recommend changes in the standard clinical management of schizophrenia on the basis of the data provided herein, in view of the small sample and open-label nature of the report. PMID- 11199944 TI - Ziprasidone in the short-term treatment of patients with schizoaffective disorder: results from two double- blind, placebo-controlled, multicenter studies. AB - This study assessed the efficacy of ziprasidone for the treatment of schizoaffective disorder. Data were taken from subsets of patients with schizoaffective disorder, derived from two separate double-blind, placebo controlled, parallel-group, multicenter studies. A total of 115 hospitalized patients with an acute episode of schizoaffective disorder were randomly assigned to receive either fixed oral doses of ziprasidone 40 mg/day (N = 16), 80 mg/day (N = 18), 120 mg/day (N = 22), 160 mg/day (N = 25), or placebo (N = 34) for 4 to 6 weeks. Mean baseline-to-endpoint changes in Brief Psychiatric Rating Scale (BPRS) total, BPRS Core, Clinical Global Impressions Severity scale (CGI-S), BPRS Depressive, BPRS Manic, and Montgomery-Asberg Depression Rating Scale total scores were compared between the placebo and ziprasidone groups. Neurological (Simpson-Angus, Barnes Akathisia, Abnormal Involuntary Movement Scale [AIMS]) and other side effects were also assessed. Significant dose-related improvements on all primary efficacy variables (BPRS total, BPRS Core, CGI-S) and for BPRS Manic items were observed with ziprasidone treatment in a combined analysis of data from both studies (p < or = 0.01). Ziprasidone 160 mg/day was significantly more effective than placebo in improving mean BPRS total, BPRS Core, BPRS Manic, and CGI-S scores (p < 0.05). At 120 mg/day, ziprasidone was significantly more effective than placebo in improving mean CGI-S scores (p < 0.05). The incidence of individual adverse events was generally low in all treatment groups and was not dose-related. In addition, no significant differences were observed between baseline-to-endpoint mean changes in Simpson-Angus and AIMS scores with placebo or ziprasidone 40 to 160 mg/day. These results suggest that ziprasidone may have efficacy in the treatment of affective as well as psychotic symptoms of schizoaffective disorder, with a low side-effect burden. PMID- 11199945 TI - Augmentation of fluoxetine's antidepressant action by pindolol: analysis of clinical, pharmacokinetic, and methodologic factors. AB - In a controlled trial, the beta-adrenoceptor/5-hydroxytryptamine-1A (5-HT1A) receptor antagonist pindolol accelerated and enhanced the antidepressant effect of fluoxetine. The median times to sustained response (> or = 50% reduction of baseline severity maintained until endpoint) were 19 days for fluoxetine plus pindolol (N = 55) and 29 days for fluoxetine plus placebo (N = 56) (p = 0.01). The response rate at endpoint was 16% greater in patients treated with the combination. The plasma concentration of pindolol remained stable between 3 days (first blood sampling) and 6 weeks. Mean values were approximately 26 nM, a concentration higher than the Ki of (-)pindolol for human 5-HT1A autoreceptors (11 nM). Plasma fluoxetine and norfluoxetine concentrations increased steadily until the fourth week of treatment. Fluoxetine concentrations were lower in patients receiving the combination (p = 0.043), but there was no significant relationship to the clinical response in either group. A reanalysis of the data using a survival analysis revealed that significant differences in the time to sustained response between both groups would have also been detected (1) in a 2 week trial, (2) without a placebo lead-in phase, and (3) with less frequent visits. However, the use of "response" instead of "sustained response" as measure of clinically relevant change would have greatly diminished the difference between treatment arms (p = 0.08 instead of p = 0.01). This emphasizes the need of using stringent outcome criteria in antidepressant drug trials. A comparison of the data of all sustained responders (N = 27) in the fluoxetine-plus-placebo group with the first 27 responders in the fluoxetine-plus-pindolol group (of a total of 38) revealed a highly significant difference in the time to sustained response (18 and 10 days, respectively; p = 0.0002). This indicates that the faster response in the fluoxetine-plus-pindolol group is not a result of the greater proportion of responders. PMID- 11199946 TI - Mitchell B. Balter Award. Human leukocyte antigen-A1 predicts a good therapeutic response to clozapine with a low risk of agranulocytosis in patients with schizophrenia. AB - Several studies indicate an association between human leukocyte antigens (HLA) and clozapine-induced agranulocytosis. The authors have previously reported a significantly increased frequency of HLA-A1 among patients with schizophrenia who do not respond to conventional drugs, but do respond to clozapine treatment. In this study, the authors addressed the question of whether the same association is found in patients developing granulocytopenia or agranulocytosis. The frequency of the HLA-A1 allele in patients with clozapine-induced agranulocytosis or granulocytopenia was low (11.5%), whereas HLA-A1 was associated with a good therapeutic response to clozapine at an allele frequency of 58%. The frequency of HLA-A1 is 20% in the Finnish population. These results suggest that HLA-A1 may predict a good therapeutic outcome and a low risk of agranulocytosis and, thus, enable defining a subgroup of patients with schizophrenia in whom clozapine treatment could be started early to stop the disease from progressing. PMID- 11199947 TI - Long-term treatment of obsessive-compulsive disorder after an acute response: a comparison of fluoxetine versus placebo. AB - Few controlled studies have evaluated the long-term continuation of pharmacotherapy for relapse prevention in patients with obsessive-compulsive disorder (OCD). This study assessed efficacy and safety of fluoxetine versus placebo in preventing relapse of OCD during a 52-week period in responders to short-term administration of fluoxetine. Patients who met DSM-IV criteria for OCD and had a Yale-Brown Obsessive Compulsive Scale score > or = 19 were treated with single-blind fluoxetine 20, 40, or 60 mg/day (based on physician assessment of response and tolerability). After 20 weeks, responders were randomly assigned to receive continued treatment with fluoxetine or placebo and were monitored for relapse for up to 52 weeks. Of 130 patients who entered the study, 71 (55%) were randomly assigned to receive fluoxetine (N = 36) or placebo (N = 35). Patients who received fluoxetine had numerically lower relapse rates compared with those who received placebo, although the difference was not significant (Kaplan-Meier 1 year relapse rates: fluoxetine, 20.6%; placebo, 31.9%; one-tailed p value = 0.137). In additional analyses evaluating patients on the basis of fluoxetine dose at randomization, patients who continued treatment with fluoxetine 60 mg/day (N = 52) had significantly lower rates of relapse than those who were switched to placebo (Kaplan-Meier 1-year relapse rates: fluoxetine, 17.5%; placebo, 38.0%; one-tailed p value = 0.041). Those who responded to the acute treatment phase with 40 (N = 18) or 20 (N = 1) mg/day had low overall rates of relapse, and the difference between continued fluoxetine and placebo treatment for these patients was not significant. For responders to the 60 mg/day dosage, those patients who continued treatment with fluoxetine were provided greater protection against relapse than those patients switched to placebo. PMID- 11199948 TI - Increased 5-hydroxytryptamine-2 receptor binding in the frontal cortex of depressed patients responding to paroxetine treatment: a positron emission tomography scan study. AB - The changes in aminergic receptors elicited by antidepressant treatments have been extensively examined in the brain of experimental animals using radioligand and molecular techniques. However, there is a very limited direct information regarding the changes effected by such treatments in the human brain, as well as its relationship to clinical improvement. Using positron emission tomography (PET) scanning, the authors examined the cortical 5-Hydroxytryptamine-2A (5-HT2A) receptor binding of [18F]fluoro-ethyl-spiperone after a 4-week treatment with the selective serotonin reuptake inhibitor paroxetine. [18F]fluoro-ethyl-spiperone labels 5-HT2A receptors in the cortex and dopamine D2 receptors in the basal ganglia. A binding index (BI) was calculated in the frontal cortex and the basal ganglia (mostly caudate-putamen) by reference to cerebellum. Thirty-seven inpatients with major depression with a mean +/- SD score on the 21-item Hamilton Rating Scale for Depression (HAM-D-21) of 26.3 +/- 4.3 at admission were treated with paroxetine 40 mg/day. After 4 weeks of treatment, the BI in the frontal cortex of remitted patients (HAM-D-21 score = 4.7 +/- 4.0; N = 20) was significantly greater than the score in nonresponder patients (HAM-D-21 score = 21.2 +/- 4.0; N = 17) (BI = 0.54 +/- 0.15 and 0.41 +/- 0.17, respectively; p < 0.02). No such difference was observed in the basal ganglia (5.45 +/- 1.11 and 5.39 +/- 0.82, respectively; p = 0.85). The significant difference in cortical BI persisted when age was used as covariate (p < 0.016). These data suggest that clinical improvement in patients treated with paroxetine is associated with an increase in the density of 5-HT2A receptors in the frontal cortex. PMID- 11199949 TI - Opipramol for the treatment of generalized anxiety disorder: a placebo-controlled trial including an alprazolam-treated group. AB - Opipramol, a drug widely prescribed in Germany, is a tricyclic compound with no reuptake-inhibiting properties. However, it has pronounced D2-, 5-HT2-, and H1 blocking potential and high affinity to sigma receptors (sigma-1 and sigma-2). In early controlled trials, anxiolytic effects were revealed. However, those studies were performed before the concept of generalized anxiety disorder (GAD) was established. Because of the interesting receptor-binding profile and promising results of the early clinical trials, the authors performed a state-of-the-art placebo-controlled trial using alprazolam as an active control. Three hundred seven outpatients with GAD were included. After a 7-day single-blind placebo washout, patients were randomly assigned to receive either opipramol (final dose, 200 mg/day), alprazolam (2 mg/day), or placebo and were treated for 28 days. The efficacy of both active compounds was higher than the effects with placebo treatment. There were statistically significant differences (p < 0.05, according to the analysis of covariance) in the main outcome criterion (baseline-adjusted final means of an intent-to-treat analysis of the total scores on the Hamilton Rating Scale for Anxiety) and in secondary efficacy parameters, with global improvement of 47% for placebo and significantly more for opipramol (63%) and alprazolam (64%). Regarding safety and tolerability, no substantial differences in the number of adverse events observed between treatment groups were obvious. Sedation seemed more pronounced with alprazolam treatment than with opipramol or placebo. In this trial, it was demonstrated for the first time that opipramol, a strong but nonselective sigma site ligand, possesses anxiolytic efficacy superior to placebo in the treatment of GAD. PMID- 11199950 TI - No difference in brain activation during cognitive performance between ecstasy (3,4-methylenedioxymethamphetamine) users and control subjects: a [H2(15)O] positron emission tomography study. AB - The long-term use of the serotonin-releaser and uptake-inhibitor 3,4 methylenedioxymethamphetamine (MDMA, "Ecstasy") has been associated with memory impairments and increased liability to depressive mood and anxiety attacks. It is unclear, however, whether these psychologic deviations are reflected in alterations of the underlying neurophysiologic substrate. The authors compared mood and regional cerebral blood flow (rCBF) profiles between regular polytoxic Ecstasy users and Ecstasy-naive controls. Brain activity as indexed by rCBF was measured during cognitive activation by an attentional task using positron emission tomography and [H2(15)O]. Mood was assessed by means of the Hamilton Rating Scale for Depression (HAM-D) and the EWL Mood Rating Scale. Statistical parametric mapping revealed that brain activity did not differ between the two groups. Both groups also performed equally on the cognitive task requiring sustained attention. However, significantly higher levels of depressiveness as determined by the HAM-D and EWL scales were found in Ecstasy-using subjects. These data indicate that, despite differences in mood, polytoxic Ecstasy users do not differ from Ecstasy-naive controls in terms of local brain activity. Heightened depressiveness in the Ecstasy group was consistent with results from previous studies and could be related to serotonergic hypofunction resulting from repeated MDMA consumption. However, this study cannot exclude the possibility that the observed differences are preexisting rather than a result of Ecstasy use. PMID- 11199951 TI - Posttreatment results of combining naltrexone with cognitive-behavior therapy for the treatment of alcoholism. AB - Naltrexone, an opiate antagonist medication, has been reported to be efficacious in the treatment of alcohol dependence when added to psychosocial treatments. Although the within-treatment efficacy of naltrexone has received primary attention, there has been little published on the outcome of individuals once the medication is discontinued. Animal studies have led to concern regarding a quick rebound to heavy drinking. This report extends the data previously reported by evaluating the outcome in alcoholic subjects during the 14 weeks after a 12-week treatment with naltrexone or placebo in conjunction with cognitive behavioral therapy. Of the 131 subjects evaluated during the treatment phase, 124 (95%) had up to 14 weeks of posttreatment drinking data available for analysis. Measures of craving and blood markers of heavy drinking were also evaluated. By the end of treatment, naltrexone demonstrated significantly greater efficacy than placebo. However, once the medication was discontinued, there was a gradual increase in relapse rates, heavy drinking days, and drinks per drinking day, and fewer days of abstinence were reported. By the end of the 14-week follow-up period, although naltrexone-treated subjects were, on average, still doing better than control subjects, the effectiveness of naltrexone was no longer statistically significant. There was no evidence that naltrexone subjects had an immediate return to heavy alcohol use as suggested in animals. These data suggest that, for a number of alcoholic subjects, continued treatment with naltrexone, or perhaps psychosocial intervention, for longer than 3 months is indicated. Future research should identify which alcohol-dependent individuals may need prolonged treatment to improve treatment success in the long term. PMID- 11199952 TI - The relationship between mood state and plasma methadone concentration in maintenance patients. AB - Although methadone maintenance is designed to stabilize opioid-dependent patients, some experience significant withdrawal in the latter part of the 24 hour interdosing interval. This study was designed to determine the mood changes that maybe associated with such withdrawal. Eighteen methadone patients, nine of whom experienced significant withdrawal, were tested over a single interdosing interval. During this time, 13 blood samples were collected to measure plasma racemic methadone concentrations, and the Profile of Mood States (POMS) was administered on 11 of these occasions. The POMS was also administered on 11 occasions over 24 hours to 10 drug-free healthy controls. In comparison with controls, methadone patients showed increased anger, depression, tension, confusion, and fatigue, as well as decreased vigor. For all scales, maximal differences from controls occurred at times of trough methadone concentration and minimal differences around the time of peak concentration. Changes in mood over the interdosing interval were more exaggerated in the nine patients who experienced significant withdrawal compared with those who did not. The composite Total Mood Disturbance (TMD) scores were calculated for each subject at each time point. The sigmoid Emax model was used to relate plasma concentrations to these data and to calculate the slope factor (N). This model could be fitted for 14 of the 18 patients with a mean +/- SEM slope factor of 2.2 +/- 0.5. TMD score was also shown to be inversely related to the rate of decline in methadone concentration from peak to trough. These results show that significant mood changes occur in response to changes in methadone concentration, and these are more pronounced in those who experience withdrawal. The concentration-effect relationships suggest that relatively small changes in plasma concentration will result in significant mood change. Differences in the degree of mood change between those who do and do not experience significant withdrawal may be explained by variation in the rate of decline in plasma concentration from peak to trough. PMID- 11199953 TI - Effects of newer atypical antipsychotics on autonomic neurocardiac function: a comparison between amisulpride, olanzapine, sertindole, and clozapine. AB - As part of a prospective clinical study investigating the effects of atypical neuroleptics on autonomic neurocardiac function (ANF), serial standardized recordings of conventional electrocardiograms and computer-calculated measurements of 5-minute resting heart rate variability (HRV) were obtained from 51 medication-free inpatients with schizophrenia (DSM-III-R-diagnosed) before and after an average of 14.1 days of treatment with amisulpride 400 mg/day (N = 12), olanzapine 20 mg/day (N = 13), sertindole 12 mg/day (N = 13), or clozapine 100 mg/day (N = 13). Reference values for the HRV data were obtained from a large group of well-matched healthy controls (N = 70). The most important findings were the following: (1) clozapine, olanzapine, and sertindole all prolonged mean frequency-corrected QTc times, which, in the case of sertindole, proved to be significant (Wilcoxon test p <0.05); (2) sertindole and clozapine significantly increased the mean resting heart rate; and (3) only clozapine significantly reduced the parasympathetic resting tone. The results of the HRV studies are discussed considering the in vitro receptor profiles of the atypical neuroleptics under study. Potential implications for the cardiac safety and tolerance of these drugs are also discussed. PMID- 11199954 TI - The effect of extract of ginkgo biloba added to haloperidol on superoxide dismutase in inpatients with chronic schizophrenia. AB - The purpose of the study was to evaluate the effect of the classic antipsychotic haloperidol plus extract of ginkgo biloba (EGb) on treatment-resistant chronic schizophrenia and on blood superoxide dismutase (SOD) levels. Eighty-two patients with chronic refractory schizophrenia were studied. Forty-three patients were treated with haloperidol plus extract of ginkgo biloba (group 1), and 39 received haloperidol plus placebo (group 2). SOD levels of these patients were measured before and after treatment and were compared with SOD levels of 30 healthy volunteers. Therapeutic efficiency was equated with a change in clinical rating scores assessed by standardized measurement tools that included the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms (SANS) over this period. Patients in group 1 improved significantly as demonstrated by scores from these two assessment instruments; those in group 2 improved significantly only as shown by scores on SANS. SOD levels before treatment in all patients were significantly higher than those in healthy controls; after treatment, the SOD level decreased significantly in group 1 but not in group 2. These results suggest that EGb may enhance the efficiency of the classic antipsychotic haloperidol in patients with schizophrenia, especially on their positive symptoms, and that EGb may work through an antioxidant effect that is involved in the therapeutic mechanism in patients with chronic refractory schizophrenia. PMID- 11199955 TI - The effects of concomitant phenytoin administration on the steady-state pharmacokinetics of quetiapine. AB - Quetiapine fumarate ('Seroquel') is a newly introduced atypical antipsychotic with demonstrated efficacy in the treatment of positive and negative symptoms of schizophrenia. It is extensively metabolized, predominantly by cytochrome P450 3A4. Therefore, concurrent administration of drugs that induce or inhibit this enzyme may affect quetiapine pharmacokinetics. This study demonstrated that the potent cytochrome P450 enzyme-inducer phenytoin did indeed have a marked effect on the metabolism of quetiapine, resulting in a 5-fold increase in clearance when administered concomitantly to patients with DSM-IV-diagnosed schizophrenia, schizoaffective disorder, or bipolar disorder. These results indicate that dosage adjustment of quetiapine may be necessary when the two drugs are given concurrently and that caution may be required when administering other drugs that inhibit or induce cytochromes, particularly P450 3A4. PMID- 11199956 TI - A preliminary study of bupropion sustained-release for smoking cessation in patients with chronic posttraumatic stress disorder. AB - This study was conducted to evaluate the effect of bupropion sustained-release (SR) on smoking cessation in patients with chronic posttraumatic stress disorder (PTSD). Fifteen veterans with chronic PTSD who desired to stop smoking enrolled in a 12-week double-blind evaluation of bupropion SR and placebo. Patients were randomly assigned in a 2:1 ratio to receive either bupropion SR or placebo. Bupropion SR was initiated at 150 mg daily for 3 or 4 days and increased to a final dose of 150 mg twice daily (300 mg daily total). Ten patients received bupropion SR and five received placebo. Nine of the patients who received bupropion SR were already being treated with at least one other psychotropic medication. One of the ten patients did not complete the study because of medication side effects. Eighty percent of patients receiving bupropion SR successfully stopped smoking by the end of week 2, and 6 (60%) of these 10 maintained smoking cessation at the study endpoint (week 12). At the 6-month follow-up, 40% of the patients (4 of 10) who received bupropion SR maintained smoking cessation. One (20%) of the five patients who received placebo stopped smoking and maintained smoking cessation at the 6-month follow-up. Bupropion SR was generally well-tolerated in combination with other psychotropic medications. Bupropion SR may be effective in helping patients who desire to quit smoking and who also have a concomitant anxiety disorder, such as PTSD. PMID- 11199958 TI - Enhanced TOF-SIMS imaging of a micropatterned protein by stable isotope protein labeling. AB - Patterning of biomolecules on surfaces is an increasingly important technological goal. Because the fabrication of biomolecule arrays often involves stepwise, spatially resolved derivatization of surfaces, spectroscopic imaging of these arrays is important in their fabrication and optimization. Although imaging time of-flight secondary ion mass spectrometry (TOF-SIMS) is a powerful method for spatially resolved surface analysis, TOF-SIMS images of micropatterned proteins on organic substrates can be difficult to acquire, because of the lack of high intensity, protein-specific molecular ions that are essential for imaging under static conditions. In contrast, low-mass ions are of suitable intensity for imaging, but can originate from different chemical species on the surface. A potential solution to this problem is to utilize stable isotope labeled proteins, an approach that has heretofore not been explored in TOF-SIMS imaging of micropatterned proteins and peptides. To investigate the feasibility of stable isotope enhanced TOF-SIMS imaging of proteins, we synthesized 15N-labeled streptavidin by labeling of the protein during expression from a recombinant gene. The spatial distribution of streptavidin bound to biotin micropatterns, fabricated on a polymer and on a self-assembled monolayer on gold, was imaged by TOF-SIMS. Imaging of high-intensity, low-m/z secondary ions (e.g., C15N-) unique to streptavidin enabled unambiguous spatial mapping of the micropatterned protein with a lateral resolution of a few micrometers. TOF-SIMS imaging of micropatterned 15N-labeled streptavidin also illustrated the exquisite sensitivity of TOF-SIMS to low fractional coverage of protein (5 A effective thickness) in the background regions of the protein micropattern. PMID- 11199957 TI - Effects of bupropion sustained-release on sexual functioning and nocturnal erections in healthy men. AB - Many antidepressants are known to cause adverse sexual effects. Bupropion is an antidepressant with fewer reported adverse sexual effects. Studies of sexual side effects are often confounded by psychiatric and medical conditions affecting sexual function. In this study, the effects of bupropion on subjective and objective sexual functioning were measured in healthy men. Thirteen men without psychiatric or medical illness completed a 2-week, placebo-controlled, double blind, crossover trial of bupropion sustained-release 300 mg/day. Subjects had a 1-week washout period between trials. Sexual function was measured using a validated, self-administered questionnaire and the RigiScan, an instrument measuring nocturnal penile tumescence and rigidity. No differences were found in self-reported sexual function, number of erections, total erection time, or penile rigidity in subjects taking bupropion compared with those taking placebo or baseline. These findings support that bupropion does not have subjective adverse sexual side effects and does not affect nocturnal erections in healthy men. PMID- 11199959 TI - Full phase analysis of portland clinker by penetrating synchrotron powder diffraction. AB - Fabrication of portland cements commonly depends on X-ray fluorescence (XRF), which measures the elemental compositions. XRF is used to adjust the raw material proportions and to control the process conditions. However, to predict the mechanical strength of the resulting concrete, it is essential to know the phase composition which is, so far, indirectly inferred by the Bogue method. Here, we report a phase analysis of an industrial portland clinker containing six crystalline phases, Ca3SiO5, Ca2SiO4, Ca4Al2Fe2O10, Ca3Al2O6, NaK3(SO4)2, and CaO, by Rietveld refinement of synchrotron X-ray powder diffraction data (lambda = 0.442377 A). Even the minor component, CaO 0.45(2)%, was readily analyzed. We have also carried out a phase study of the same clinker with laboratory X-rays to characterize the changes in the detection limit and errors. Furthermore, by adding a suitable crystalline standard to the same clinker, we have determined the overall amorphous phase content. The procedure established for this state-of the-art phase analysis shows the high precision that can be achieved by using penetrating X-rays, which is of interest not only in cement chemistry but in other industrially important multiphase systems such as slags, superalloys, or catalysts. PMID- 11199960 TI - Microchannel DNA sequencing matrices with a thermally controlled "viscosity switch". AB - Polymers and hydrogels that swell or shrink in response to environmental stimuli such as changes in temperature, pH, or ionic strength are of interest as switchable materials for applications in biotechnology. In this paper, we show that thermoresponsive polymers offer some particular advantages as entangled matrices for DNA sequencing by capillary and microchip electrophoresis. Matrices based on conventional water-soluble polymers demand a compromise in their design for microchannel electrophoresis: whereas highly entangled solutions of high molar mass polymers provide optimal sequencing performance, their highly viscous solutions require application of high pressures to be loaded into electrophoresis microchannels. Here, we demonstrate the reproducible synthesis, precise characterization, and excellent DNA sequencing performance of high molar mass, thermoresponsive polymer matrices that exhibit a reversible, temperature controlled "viscosity switch" from high-viscosity solutions at 25 degrees C to low-viscosity, microphase-separated colloidal dispersions at a chosen, elevated temperature. The viscosity switch decouples matrix loading and sieving properties, enabling acceleration of microchannel flow by 3 orders of magnitude. DNA sequencing separations yielding read lengths of 463 bases of contiguous sequence in 78 min with 97% base-calling accuracy can be achieved in these matrices. Switchable matrices will be particularly applicable to microfluidic devices with dynamic temperature control, which are likely to provide the next major leap in the efficiency of high-throughput DNA analysis. PMID- 11199961 TI - Fabrication of phospholipid bilayer-coated microchannels for on-chip immunoassays. AB - Herein we describe a new class of microfluidic immunoassays based upon solid supported lipid bilayers. Two-dimensionally fluid bilayer material, which can accommodate multivalent binding between surface-bound ligands and aqueous receptors, was coated on the surface of poly(dimethylsiloxane) microchannels. The bilayers contained dinitrophenyl (DNP)-conjugated lipids for binding with bivalent anti-DNP antibodies. Twelve independent data points of surface coverage versus bulk protein concentration could be made simultaneously by forming a linear array of channels and flowing fluorescently labeled antibodies into them. This enabled an entire binding curve to be obtained in a single experiment. The measured apparent binding constant for the DNP/anti-DNP system was 1.8 microM. The methodology for performing heterogeneous assays developed here not only produces rapid results but also requires much less protein than traditional procedures and eliminates some standard sources of experimental error. PMID- 11199962 TI - Analysis of protein phosphorylation by a combination of elastase digestion and neutral loss tandem mass spectrometry. AB - Loss of phosphoric acid is the most effective fragmentation reaction of pSer- and pThr-containing phosphopeptides of small size (up to 10-15 residues) in low energy collision-induced dissociation. Therefore, tandem mass spectrometry with neutral loss scanning was evaluated for its utility to analyze protein phosphorylation using protein kinase A (PKA) catalytic subunit, which is phosphorylated at Thr197 and Ser338, as an example. Analysis of tryptic digests of phosphoproteins by tandem mass spectrometry with scanning for neutral loss of phosphoric acid resulted in spectra with poor signal-to-noise ratio, mainly because of the large size of the phosphopeptides formed (>2 kDa). This unfavorable size was caused by the distribution of tryptic cleavage sites in PKA and by interference of phosphorylation with tryptic cleavage. To generate a set of smaller peptide fragments, digestion was performed using the low-specificity protease elastase. Analysis of the total elastase digest with neutral loss scanning resulted in observation of a set of partially overlapping phosphopeptides with high abundance, providing a complete coverage of PKA phosphorylation sites. The peptide size generated by elastase (0.5-1.5 kDa) is ideally suited for this scan mode, which was found to provide the highest specificity for detection of singly charged phosphopeptides (neutral loss of 98). Identification of the PKA phosphorylation sites was performed by mass spectrometric sequencing of the elastase-derived phosphopeptides, which provided highly informative product ion spectra. PMID- 11199963 TI - Ion trap/ion mobility/quadrupole/time-of-flight mass spectrometry for peptide mixture analysis. AB - An ion trap/ion mobility/quadrupole/time-of-flight mass spectrometer has been developed for the analysis of peptide mixtures. In this approach, a mixture of peptides is electrosprayed into the gas phase. The mixture of ions that is created is accumulated in an ion trap and periodically injected into a drift tube where ions separate according to differences in gas-phase ion mobilities. Upon exiting the drift tube, ions enter a quadrupole mass filter where a specific mass to-charge (m/z) ratio can be selected prior to collisional activation in an octopole collision cell. Parent and fragment ions that exit the collision cell are analyzed using a reflectron geometry time-of-flight mass spectrometer. The overall configuration allows different species to be selected according to their mobilities and m/z ratios prior to collision-induced dissociation and final MS analysis. A key parameter in these studies is the pressure of the target gas in the collision cell. Above a critical pressure, the well-defined mobility separation degrades. The approach is demonstrated by examining a mixture of tryptic digest peptides of ubiquitin. PMID- 11199965 TI - Correction of H3+ contributions in hydrogen isotope ratio monitoring mass spectrometry. AB - Two fundamentally different approaches, termed "pointwise" and "peakwise," are currently used to correct hydrogen isotope ratio monitoring data for the presence of H3+ ion contributions. Consideration of the underlying assumptions shows that the peakwise approach is valid only for peaks with the same functional shape and only when background signals do not vary. The pointwise correction is much more versatile and can be used even when peak shapes and sizes, as well as background signals, vary significantly. It is not exact and is limited in accuracy by (1) the signal-broadening effects of electronic time constants, (2) the analog-to digital conversion frequency, and (3) the highest frequency of the sample signal. To minimize errors for typical gas chromatographic signals, time constants of <500 ms and analog-to-digital sampling intervals of < or =250 ms are needed. Errors are further minimized by matching sample and standard peaks in both amplitude and D/H ratio. Using the pointwise algorithm, we demonstrate that a series of 14 homologous n-alkanes varying in concentration over a 5-fold range can be analyzed with a mean precision of 2.3 per thousand and no systematic errors. PMID- 11199964 TI - A method for quantification from composite spectra: application to the determination of isomeric DNA photoproducts by tandem mass spectrometry. AB - Quantification of mixture components from their composite optical or mass spectra is a common need in analytical chemistry. We encountered the need when applying a combination of enzymatic digestion with nuclease P1 and tandem mass spectrometry to a mixture of isomeric photomodified oligodeoxynucleotides. In the procedure, we collisionally activated the [M - H]- or [M + Na - 2H]- ion of trinucleotide triphosphates, which were extricated enzymatically from the larger, damaged oligodeoxynucleotides, and we measured the relative abundances of characteristic fragment ions. The results sometimes yield curved calibrations for plots of the relative fragment ion abundances in the product ion spectra of isomers versus their relative amounts. We developed a normalized linear model, which brings understanding to the nonlinear plots and allows quantification of the mixture components from their composite spectra. The outcome demonstrates a general quantification procedure and shows that different yields for generating fragment ions from different constituents of the mixture cause the curved calibration lines. PMID- 11199966 TI - Determination of the the H3 factor in hydrogen isotope ratio monitoring mass spectrometry. AB - The H3 factor, K, is a parameter required in high-precision, mass spectrometric analyses of hydrogen isotopic abundances. When H2 is used as the sample gas, R* = R - Ki2, where R* is the true HD/H2 ratio, R is the observed (mass 3)/(mass 2) ion-current ratio, and i2 is the ion current at mass 2. Four different methods for the determination of K were defined and tested under conditions characteristic of isotope ratio monitoring systems. Three of these were peak based. The fourth employed steady flows of H2 from a conventional inlet system. Results obtained using the latter method were more precise (standard deviation of K = 0.1 versus approximately 0.6 ppm mV(-1) for the peak-based methods). However, use of the resulting values of K for correction of isotope ratio monitoring GC/MS results led to systematic errors as large as 9 per thousand, whereas use of the peak-based values led to no systematic errors. Values of K were only weakly dependent on the pressure of He, declining approximately 5% for each 10-fold increase in P(He). Small variations in partial pressures of H2O and CH4, potential contaminants under isotope ratio monitoring conditions, had no significant effect on values of K. PMID- 11199967 TI - Predicting electrospray response from chromatographic retention time. AB - The relationship between electrospray ionization response and HPLC retention time was explored. For the series of small peptides studied, higher ESI response was observed for analytes with longer reversed-phase HPLC retention times. This correlation existed for both experimentally measured retention times and those calculated from amino acid retention coefficients. This study is useful t PMID- 11199968 TI - Signal amplification using "spot-on-a-chip" technology for the identification of proteins via MALDI-TOF MS. AB - The presented "spot-on-a-chip" technology enables easy enrichment of samples in the low nanomolar (1-5 nM) range and provides a fast and reliable automated sample preparation method for performing matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis with high sensitivity and throughput. Through microdispensing, which allows accurate deposition of 60-pL droplets, dilute samples were enriched by making multiple droplet depositions in nanovials. The sample was confined to a defined spot area (300 x 300 microm), and multiple depositions increase the surface density of analyte in the nanovial, thereby providing detection of low attomole levels. The impact of the nanovial geometry with respect to the MALDI-TOF MS resolution for peptides deposited in the microfabricated silicon vials was investigated and the optimal geometry and size were determined. The spot-on-a chip technology, that is, the combination of microdispensing, micromachined silicon nanovials and on-spot enrichment provides a signal amplification of at least 10-50 times as compared to an ordinary sample preparation. The linearity of the enrichment effect is shown by the analysis of a peptide mixture at the 5 nM level. The signal amplification provided by the spot-on-a-chip enrichment is demonstrated by the analysis of relevant biological samples, interleukin-8 from a spiked cell supernatant, and by successful protein identification of an excised spot from a high-sensitivity silver-stained two-dimensional electrophoresis gel separation. PMID- 11199969 TI - Sulfur isotope analysis of sulfide and sulfate minerals by continuous flow isotope ratio mass spectrometry. AB - A continuous flow method (CF-IRMS) for the rapid determination of the sulfur isotope composition of sulfide and sulfate minerals has significant advantages over the classic extraction method in terms of the reduced sample quantity and a rapid analytical cycle of less than 8 min/ analysis. For optimum performance, the technique is sensitive to a number of operating parameters, including sample weight and the O2 saturation of the Cu-reduction reactor. Raw data are corrected using a calibration based on five international and internal standards ranging from -17.3 to +20.3 per thousand, which requires monitoring in order to correct the effect of changing delta18O of the sample gas on the measured mass 66 values. Measured sulfur contents are within 1-1.5% of expected values and the reproducibility of delta34S values is +/-0.1 per thousand (1sigma). The technique has been used successfully for more than 1000 analyses of geological samples with a wide range of delta34S from -20 to +20 per thousand. PMID- 11199970 TI - Secondary ion mass spectrometry of zeolite materials: observation of abundant aluminosilicate oligomers using an ion trap. AB - Oligomeric oxyanions were observed in the secondary ion mass spectra (SIMS) of zeolite materials. The oxyanions have the general composition AlmSinO2(m+n)H(m 1)(-)(m+n = 2 to 8) and are termed dehydrates. For a given mass, multiple elemental compositions are possible because (Al + H) is an isovalent and isobaric substitute for Si. Using 18 keV Ga+ as a projectile, oligomer abundances are low relative to the monomers. Oligomer abundance can be increased by using the polyatomic projectile ReO4- (approximately 5 keV). Oligomer abundance can be further increased using an ion trap (IT-) SIMS; in this instrument, long ion lifetimes (tens of ms) and relatively high He pressure result in significant collisional stabilization and increased high-mass abundance. The dehydrates rapidly react with adventitious H2O present in the IT-SIMS to form mono-, di-, and trihydrates. The rapidity of the reaction and comparison to aluminum oxyanion hydration suggest that H2O adds to the aluminosilicate oxyanions in a dissociative fashion, forming covalently bound product ions. In addition to these findings, it was noted that production of abundant oligomeric aluminosilicates could be significantly increased by substituting the countercation (NH4+) with the larger alkali ions Rb+ and Cs+. This constitutes a useful tactic for generating large aluminosilicate oligomers for surface characterization and ion molecule reactivity studies. PMID- 11199971 TI - Compositional analysis of glycosaminoglycans by electrospray mass spectrometry. AB - The purpose of this work is to analyze glycosaminoglycans (GAGs) directly from complex mixtures without the need to purify individual components. Novel conditions for negative ion electrospray MS of chondroitin sulfate (CS) oligosaccharides are described in which sodium adduction and fragmentation are avoided. Differentiation between positional sulfation isomers is demonstrated for CS disaccharides, and a selected reaction monitoring scheme is used to quantify sulfation isomers in disaccharides liberated from decorin and biglycan. A size exclusion chromatography LC/MS method is shown to be effective for compositional analysis of longer CS oligosaccharides. The SEC step serves to simplify the composition of GAGs entering the mass spectrometer at any time, thus allowing the masses of the constituent molecules to be extracted. Mass spectrometric detection produces far more information than conventional UV or fluorescent detectors and allows the monosaccharide composition of individual components to be determined. PMID- 11199972 TI - Control of electrochemical reactions at the capillary electrophoresis outlet/electrospray emitter electrode under CE/ESI-MS through the application of redox buffers. AB - It was found that combining capillary electrophoresis (CE) and electrospray ionization mass spectrometry (ESI-MS) overlays two controlled current techniques to form a three-electrode system (CE inlet, CE outlet/ES emitter, and MS inlet electrodes) in which the CE outlet electrode and the ES emitter electrode were shared between the CE and the ESI-MS circuits. Depending on the polarities and magnitudes of the voltages at the CE inlet, CE outlet/ES emitter, and MS inlet electrodes, the nature of the two redox reactions at the shared electrode was the same or different (both reduction, both oxidation, or one oxidation and the other reduction). Several redox buffers were introduced for controlling electrochemical reactions at the shared electrode. By reacting at this electrode, redox buffers were able to maintain electrode potentials below the onset of water electrolysis, thereby eliminating gas bubble formation and/or pH drift. The volume of the gas generated due to water electrolysis was used to quantitate water oxidation or reduction at this electrode. Two types of redox buffers were used. A reactive electrode with an oxidation potential below that of water was used as the electrode under anodic conditions. Also, a reactive compound with a redox potential below that of water was added to the CE and/or ESI running buffer. When the shared electrode was the anode of both CE and ESI-MS circuits, the use of iron or etched and sanded stainless steel (ss) wire, instead of platinum wire, suppressed bubble formation at the shared electrode. Under these conditions, corrosion of the Fe wire and formation of Fe2+ replaced oxidation of water, eliminating O2 gas bubble and H+ formation. When mixtures of peptides were analyzed, iron adducts of peptides were observed. For a fresh wire, however, the intensities of adduct ions were less than 3% of the protonated molecules. After a few days of operation, the intensities of the adduct ions increased to approximately 50%, due to rust formation on the Fe wire. On-column rinsing with a 40% solution of citric acid rejuvenated the Fe wire and reduced the adduct peak intensities to less than 3%. Unmodified ss wire did not quench bubble formation, which was attributed to its passivated surface. When Fe, ss, and Pt wires were used as the shared electrode under forward polarity CE and positive ESI mode, where the shared electrode acted as a cathode with respect to CE inlet and as an anode with respect to MS inlet, reduction of water at the cathodic end of the electrode and, in the case of ss and Pt wires, oxidation of water at the anodic end of the shared electrode produced a significant amount of bubbles. Under these conditions, however, a buffer containing 50 mM p-benzoquinone completely suppressed both cathodic reduction and anodic oxidation of water for CE currents up to 4 microA. Reduction of p-benzoquinone at the cathodic end of the shared electrode to hydroquinone, and oxidation of this hydroquinone at the anodic end of the electrode, replaced reduction and oxidation of water, eliminating bubble formation. A 0.1% acetic acid solution saturated with I2 was also found to suppress bubble formation at the cathode for CE currents up to 3 microA; however, strong iodine adduct ions were observed under CE/ESI-MS when a mixture of peptides was analyzed. The application of iron as an in-capillary electrode for the analysis of a peptide mixture and a protein digest demonstrated a high separation efficiency similar to when hydroquinone was used as a redox buffer. PMID- 11199973 TI - Techniques for increasing the throughput of flow injection mass spectrometry. AB - Improvements to the design and operation of a Gilson 215 multiprobe liquid handling system have resulted in a significant increase in the throughput for flow injection molecular weight characterization of combinatorial chemistry libraries. The rapid injection sequence, and subsequent increased sample throughput, is effected by directing the entire mobile-phase flow through each of the injection loops sequentially while isolating or "dead-ending" the remaining nonactive loops. This mode of operation was accomplished by incorporating column switching valves prior to and following the set of eight parallel injectors. Analysis rates are achieved without sacrificing the integrity of the flow injection peak profile as baseline resolution is maintained for all samples. Using this system, the total analysis time for a 96-well microtiter plate has been reduced to approximately 5 min. PMID- 11199974 TI - Design and performance of an ESI interface for selective external ion accumulation coupled to a Fourier transform ion cyclotron mass spectrometer. AB - The coupling of Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) with electrospray ionization has advanced the analysis of large biopolymers and provided the basis for high-throughput protein characterization (e.g., for rapid "proteome" analyses). In this work, the combination of high performance capillary liquid chromatography with FTICR mass spectrometry and external ion accumulation has been shown to increase both sensitivity and analysis duty cycle. Instrument versatility is further improved by ion preselection followed by ion accumulation in an external linear quadrupole ion trap. The interface was tested with a 3.5-T FTICR mass spectrometer and evaluated with a number of peptides and proteins whose molecular weights ranged from 500 to 66000. A significant increase in the sensitivity, duty cycle, and dynamic range over that of the previously used accumulated trapping was achieved, exhibiting a detection limit of approximately 10 zmol (approximately 6000 molecules) for smaller proteins such as cytochrome c. Capillary LC external accumulation interface with FTICR was successfully applied for the study of whole-proteome mouse tryptic digests. PMID- 11199975 TI - A thermodynamic study of the temperature-dependent elution order of cyclic alpha amino acid enantiomers on a copper(II)-D-penicillamine chiral stationary phase. AB - The reversal of the elution order of cyclic alpha-amino acid enantiomers as a function of the temperature on a copper(II)-N,S-dioctyl-D-penicillamine ligand exchange column is described. The thermodynamic parameters accounting for the retention and the separation of analytes were determined by means of van't Hoff plots. The influence of different chromatographic conditions on these parameters was investigated, showing little effect of the Cu(II) concentration in the eluent but strong influence of the organic modifier content on the separation. Further, the pH of the mobile phase was found to be a determining factor for the retention of the analytes. Based on these findings, a separation mechanism is postulated comprising the importance of complex formation for primary docking at the stationary phase, while hydrophobic interactions are crucial for chiral discrimination. PMID- 11199976 TI - Single-run capillary electrophoretic determination of inorganic nitrogen species in rainwater. AB - A capillary electrophoretic (CE) method for the simultaneous determination of nitrate, nitrite, and ammonium ions has been developed. Direct (NO3-, NO2-) and indirect (NH4+) UV detection at 214 nm in conjunction with electromigration sampling from both ends of the capillary was used. The optimized separations were carried out in 10 mmol/L imidazole sulfate, 2 mmol/L 18-crown-6, and 0.02 mmol/L tetradecyltrimethylammonium hydroxide electrolyte (pH 4.0). The method permits excellent separation of three nitrogen species in only 4 min. A 1 x 10(-4) mol/L KBr solution was used as an internal standard to limit possible electrokinetic injection biases. Experimental results showed that the use of an anionic internal standard for cationic analytes and vice versa gives only slightly better precision than analysis with no internal standard. Using Br- internal standard for NO3- and NO2- ions and K+ for NH4+, peak area RSD values decrease significantly. The proposed system was applied to the speciation of inorganic nitrogen ions in rainwater samples. The recovery tests established for external calibration and standard addition techniques using one or two internal standards were within the range 100 +/- 10%. The CE results agree with those obtained by spectrophotometric methods. PMID- 11199977 TI - Low-dispersion turns and junctions for microchannel systems. AB - Numerical methods are employed to optimize the geometry of two-dimensional microchannel turns such that the turn-induced spreading of a solute band is minimized. An inverted numerical method is first developed to compute the electric potential and local species motion in turns of arbitrary geometry. The turn geometry is then optimized by means of a nonlinear least-squares minimization algorithm using the spatial variance of the species distribution leaving the turn as the object function. This approach yields the turn geometry producing the minimum possible dispersion, subject only to prescribed constraints. The resulting low-dispersion turns provide an induced variance 2-3 orders of magnitude below that of a comparable conventional turns. Sample results are presented for 180 and 90 degrees turns, and the use of these turns to form wyes and tees is discussed. A sample 45 degrees wye is presented. The use of low dispersion turns in folding separation columns is also discussed, and sample calculations are presented for folding a column 100 microm in width and up to 900 mm in length onto a region of only 10 by 10 mm. These low-dispersion geometries are applicable to electroosmosis, electrophoresis, and some pressure-driven flows. PMID- 11199978 TI - Pulsed flow modulation for high-speed GC using a pressure-tunable column ensemble. AB - A computer-driven pressure controller is used to deliver pressure pulses to the junction point of two series-coupled columns using different stationary-phase chemistries. The column ensemble consists of a trifluoropropylmethyl polysiloxane column followed by a dimethyl polysiloxane column. Each pressure pulse causes a differential change in the carrier gas velocities in the two columns, which lasts for the duration of the pulse. A pressure pulse is used to selectively increase the separation of a component pair that is separated by the first column but coelutes from the series-coupled ensemble. If both components are on the same column when the pulse is applied, a small change in the ensemble separation occurs. If one component of the pair is on the first column and the other component is on the second column, a pressure pulse can result in a much larger change in the ensemble separation for the component pair. A model with a spreadsheet algorithm is used to predict the effects of a pressure pulse on the trajectories of component bands on the column ensemble. The effect of the initiation time of a pressure pulse is investigated for a two-component mixture that coelutes from the column ensemble. For the case where the entire pressure pulse occurs when one of the components is on the first column and the other component is on the second column, the peak separation from the ensemble increases nearly linearly with the product of the pressure pulse amplitude and the pulse duration. Peak shape artifacts are observed if the pressure pulse occurs when a solute band is migrating across the column junction point. PMID- 11199979 TI - A battery-powered notebook thermal cycler for rapid multiplex real-time PCR analysis. AB - A compact, real-time PCR instrument was developed for rapid, multiplex analysis of nucleic acids in an inexpensive, portable format. The instrument consists of a notebook computer, two reaction modules with integrated optics for four-color fluorescence detection, batteries, and a battery-charging system. The instrument weighs 3.3 kg, measures 26 x 22 x 7.5 cm, and can run continuously on the internal batteries for 4 h. Independent control of the modules allows differing temperature profiles and detection schemes to be run simultaneously. Results are presented that demonstrate rapid (1) detection and identification of Bacillus subtilis and Bacillus thuringensis spores and (2) characterization of a single nucleotide polymorphism for the hereditary hemochromatosis gene. PMID- 11199980 TI - Characterization of the polarity of reversed-phase liquid chromatographic stationary phases in the presence of 1-propanol using solvatochromism and multivariate curve resolution. AB - This work characterizes solvation effects in reversed-phase liquid chromatography in the presence of 1-propanol. The solvatochromic method combined with a multivariate curve resolution-alternating least-squares analysis method has been used to characterize two modified silica surfaces--phenyl bonded and C18 bonded silica in mobile-phase mixtures of methanol--water and acetonitrile--water in the presence of 1-propanol. The presence of a small amount of 1-propanol has been shown to affect mainly the polarity properties of the stationary phases while the mobile-phase properties are largely unaffected. The chain collapse mechanism for the C18 stationary phase at higher concentrations of water seems to be inhibited in the presence of 1-propanol, and partitioning is the predominant solute retention mechanism. The phenyl-based phase shows considerably different behavior from that of the C18 phase, and propanol appears to disrupt the pi-stacking interactions between the solute and the phenyl rings anchored to the silica support. PMID- 11199981 TI - Micro-SPE method for sample introduction in capillary HPLC/MS. AB - A new solid-phase extraction on-line device for micro-HPLC is presented. This device optimizes the injection of very dilute samples into a packed capillary column. It consists of two capillary, reversed-phase, HPLC columns of different length that can be linked together as a single chromatographic column. The first segment, only 2 cm long is connected to the HPLC injector. When disconnected from the longer column, several milliliters of an aqueous sample can be passed through at a high flow rate for fast trapping. On the basis of the retention mechanism, all suitable compounds are focused on the short column head in a sharp band. As soon as the chromatographic column is recomposed, the trapped analytes are eluted and separated at the optimal flow rate and gradient conditions. Due to the high preconcentration factor, trace-level analysis can be performed successfully. Different classes of analytes of various polarities and molecular weights can be determined, depending on the stationary phase and on the detector used. Some pesticides belonging to different classes were chosen to evaluate the performance of the device using an electron ionization mass spectrometer as HPLC detector. A fungicide in an irrigation canal water was determined at a concentration level of 4.5 microg x L(-1). PMID- 11199982 TI - Quantitative analysis of etheno-2'-deoxycytidine DNA adducts using on-line immunoaffinity chromatography coupled with LC/ES-MS/MS detection. AB - Etheno DNA adducts, including 3,N4-etheno-2'-deoxycytidine (etheno-dC), are promutagenic lesions present in normal animal and human tissues. These DNA adducts are believed to be important in the etiology of cancer. Existing methods for quantifying etheno-dC use 32p. postlabeling. Although highly sensitive, postlabeling requires the use of an energetic radioisotope and considerable time and effort. The new methodology reported here permits automated quantification of trace levels of etheno-dC in crude DNA hydrolysates on the order of 5 adducts in 10(8) normal nucleotides from 100-microg samples of DNA. This was accomplished by using on-line immunoaffinity chromatography, a reverse-phase LC separation on graphitized carbon, tandem mass spectrometric detection, and an isotopically labeled internal standard. The automated procedures permitted analysis of 4 DNA hydrolysates/hr. The sensitivity using immunoaffinity cleanup was approximately 100-fold greater than that observed when using a silica-based trapping system. The validated method was applied to the analysis of etheno-dC in commercial calf thymus DNA, untreated mouse liver, and untreated rat liver DNA. The demonstrated level of performance suggests future applicability of this method in studies of cancer in humans and experimental animals. PMID- 11199983 TI - Uniformity test of bias when the reference value contains experimental error. AB - The uniformity test of biases for analytical methods must address uncertainties in the reference method. If the uncertainty associated with the estimates of true values is significant but ignored in the test of bias equality, the type I error can exceed the prespecified error rate. In general, when biases at each concentration level are confounded with a random component (confounding bias), the usual test of bias equality tests the uniformity of the combined bias, rather than the uniformity of fixed bias-the bias without the random component. Based on a confounding model that takes both the fixed and the confounding biases into account, the actual type I error rate of the uniformity test can be calculated. To eliminate the impact of confounding bias on the uniformity test of fixed biases, a new F'-test is proposed. The new F'-test is simply adding a correction factor to the conventional F-test. The correction factor is directly related to the uncertainty associated with the estimates of true values. A simulation study is conducted to show that the proposed test can bring the type I error rate down to the prespecified level. Data from two aldehyde methods are used to demonstrate how the proposed F'-test works. Recommendations on optimal sample allocation are also provided. PMID- 11199984 TI - Spatial and spectral imaging of single micrometer-sized solvent cast fluorescent plasticized poly(vinyl chloride) sensing particles. AB - Microscale plasticized PVC particles doped with hydrophobic ionophores are prepared by solvent evaporation of aqueous suspensions of sensing cocktails (poly(vinyl chloride), plasticizer, active sensing components, and tetrahydrofuran) and tested as particulate microoptical sensors. The particles contain either only the chromoionophore ETH 2458 as active reagent or the potassium ionophore BME-44, chromoionophore ETH 5294, and lipophilic anionic sites NaTFPB. The former system functions according to an anion-hydrogen ion coextraction mechanism and shows a Hofmeister anion selectivity pattern, while the latter sensor containing additional ionophores represents the more complex, truly selective optical sensors based on ion-exchange equilibria. Single microspheres are simultaneously characterized spatially and spectrally by fluorescence microscopy, coupled to a spectrometer equipped with a CCD detector. The results indicate that these microspheres respond in complete analogy to traditional thin-film-based optodes previously reported in the literature. The introduction of small, spherical ionophore-based sensing particles that operate on the basis of bulk extraction principles holds the promise of significantly expanding the available chemical palette of microsphere-based analytical assays. PMID- 11199985 TI - Comparison of the performance of different discriminant algorithms in analyte discrimination tasks using an array of carbon black--polymer composite vapor detectors. AB - An array of 20 compositionally different carbon black--polymer composite chemiresistor vapor detectors was challenged under laboratory conditions to discriminate between a pair of extremely similar pure analytes (H2O and D2O), compositionally similar mixtures of pairs of compounds, and low concentrations of vapors of similar chemicals. Several discriminant algorithms were utilized, including k nearest neighbors (kNN, with k = 1), linear discriminant analysis (LDA, or Fisher's linear discriminant), quadratic discriminant analysis (QDA), regularized discriminant analysis (RDA, a hybrid of LDA and QDA), partial least squares, and soft independent modeling of class analogy (SIMCA). H2O and D2O were perfectly classified by most of the discriminants when a separate training and test set was used. As expected, discrimination performance decreased as the analyte concentration decreased, and performance decreased as the composition of the analyte mixtures became more similar. RDA was the overall best-performing discriminant, and LDA was the best-performing discriminant that did not require several cross-validations for optimization. PMID- 11199986 TI - Rotating electrode potentiometry: lowering the detection limits of nonequilibrium polyion-sensitive membrane electrodes. AB - A rotating electrode configuration is evaluated as a means to lower the detection limits of newly devised polyion-sensitive membrane electrodes (PSEs). Planar potentiometric polycation and polyanion PSEs are prepared by incorporating tridodecylmethylammonium chloride and calcium dinonylnaphthalenesulfonate, respectively, into plasticized PVC or polyurethane membranes and mounting disks of such films on an electrode body housed in a conventional rotating disk electrode apparatus. Rotation of the PSEs at 5000 rpm results in an enhancement in the detection limits toward heparin (polyanion) and protamine (polycation) of at least 1 order of magnitude (to 0.01 unit/mL for heparin; 0.02 microg/mL for protamine) over that observed when the EMF responses of the same electrodes are assessed using a stir-bar to achieve convective mass transport. A linear relationship between omega(-1/2), where omega is the rotating angular frequency, and C1/2, the polyion concentration corresponding to half the total maximum deltaEMF response toward the polyion species, is observed. It is further shown that the rotating polycation sensor can be used as an end-point detector to greatly enhance (relative to nonrotated indicator electrode) the analytical resolution and precision for measurement of low concentrations of heparin when such samples are titrated with protamine. The theoretical basis for lowering the detection limits by rotating PSEs is discussed based on the unique nonequilibrium response mechanism of such sensors. PMID- 11199987 TI - Electrochemical monitoring of proton transfer across liquid/liquid interfaces on the surface of graphite electrodes. AB - Equilibrium partitioning of HClO4 between aqueous solutions and benzonitrile (BN) or nitrobenzene (NB) was measured and used to evaluate the pKa of the acid in the two organic solvents. The potential drop across the BN/ H2O interface was evaluated from the known potential drop across the NB/H2O interface and the voltammetrically measured formal potential of a ferrocenium/ferrocene redox couple confined within thin layers of the two organic solvents. The voltammetric reduction of tetrachloro-1, 4-benzoquinone in thin layers of BN was used to monitor changes in the concentration of protons in the layer during proton consuming faradaic reactions. The rate of proton transfer from the aqueous to the nonaqueous phase across the BN/H2O interface was shown to be adequate to sustain proton-consuming reactions at the electrode/BN interface. PMID- 11199989 TI - An experimental evaluation of cyclic voltammetry of multicharged species at macrodisk electrodes in the absence of added supporting electrolyte. AB - The reversible reduction of [S2Mo18O62]4- to [S2Mo18O62]5- and [S2Mo18O62]6- at a glassy carbon macrodisk electrode has been studied by cyclic voltammetry in acetonitrile as a function of the concentration of [(C6H13)4N]4[S2Mo18O62] in the absence and presence of [(C6H13)4N]ClO4 as the added supporting electrolyte. Consideration is given to the influence of scan rate, reference-working electrode distance, [(C6H13)4N]4[S2Mo18O62], and electrolyte concentrations. Experimental data confirm theoretical predictions that cyclic voltammetry at a macrodisk electrode is a viable technique for studies of multiply charged electroactive species without added electrolyte, provided the influence of enhanced complexities associated with effects of increased solution resistance, the mass transport contribution from migration, and convection arising from enhanced density gradients are considered. Enhanced density gradients present in the absence of added supporting electrolyte give rise to a more marked dependence of voltammograms on the angle of the electrode and hence lead to significant distortion of wave shapes at low scan rates. The summation of all these obstacles implies that quantitative evaluation of cyclic voltammograms of multiply charged species requires significantly greater care in the absence than in the presence of added supporting electrolyte. PMID- 11199988 TI - Potentiometric polymeric membrane electrodes for measurement of environmental samples at trace levels: new requirements for selectivities and measuring protocols, and comparison with ICPMS. AB - It is here established that potentiometric polymeric membrane electrodes based on electrically neutral ionophores are useful analytical tools for heavy metal ion determinations in drinking water at nanomolar total concentrations. This means that they can compete with the most sophisticated techniques of instrumental analysis. With optimized ion-selective membranes based on the lead-selective ionophore 4-tert-butylcalix[4]arenetetrakis(thioacetic acid dimethylamide) as model example, a number of native and spiked drinking water samples are potentiometrically assessed for lead, and the results compared with ICPMS measurements. The goal of this work is to demonstrate that detection limits in real world samples are routinely achieved that are, with 1.5 ppb, at least 10 fold lower than the lead action limit imposed by the U.S. Environmental Protection Agency (15 ppb). In contrast to earlier reports, different conditioning and measuring protocols are followed, and membranes and inner filling solution of optimized composition are used. The sensors are shown to be useful for the speciation analysis of lead in water as well. Typical water samples are acidified to pH 4 to assess total lead rather than free, uncomplexed lead. For lead concentrations above 2 ppb, the values compare very well with ICPMS. Main interferences are found to be H+ and Cu2+, although Cu2+ only shows significant interference at levels around or above its own action limit (1.3 ppm), in which case the water sample would anyway show quality problems. An explicit, simplified flux model targeted to the practical use of these sensors explains the extent of expected interference. Sensors are shown to require a higher selectivity than predicted by models not considering ion fluxes, since in dilute samples, the counterdiffusion flux of lead from the membrane into the sample becomes potential determining. The model and experiments shown here are a foundation for future trace level applications of potentiometric polymeric membrane electrodes. PMID- 11199990 TI - A low-power, atmospheric pressure, pulsed plasma source for molecular emission spectrometry. AB - A low-power, plasma source-based, portable molecular emission detector is described in this paper. The detector employs a pulsed-plasma source operated at atmospheric pressure for molecular fragmentation and excitation. The plasma was generated with a home-built high-voltage pulsed power supply. The average operational power of the detector was less than 0.2 W. The effects of operational parameters such as plasma gas, voltage, and plasma gas flow rate were investigated. Molecular emission spectra of a variety of organic compounds were studied. The features of the emission spectra obtained with the pulsed plasma source were significantly different from those obtained with direct current (dc) discharge at a power higher than 10 W. The spectra obtained in this work showed strong CH emission at 431.2 nm; however, the typical CN emission observed with a conventional dc plasma source at 383-388 nm was very weak in most cases. The strong CN emission was only obtained for compounds containing nitrogen, such as aniline. Dimethyl sulfoxide can be detected at a limit of 200 ppb using helium plasma by observing the emission band of the CH radical. The detector was very stable and did not experience electrode fouling even with the introduction of organic vapors. Such a detector is very promising for organic vapor detection. PMID- 11199991 TI - Water structures in ion-exchange resin particles: solvation dynamics of Nile Blue A. AB - The structures of water, partitioned in cation-exchange resin particles, were studied on the basis of fluorescence dynamics of Nile Blue A (NB). The fluorescence lifetime of NB in the resin was longer than that in water and increased with increasing cross-linking density of the resin (rho). The results demonstrated that the water structures in the resin were significantly different from those in water and dependent on rho. A study on solvation dynamics of NB in the resin, reflecting structured water around the ion-exchange group, revealed the roles of "bound water" molecules in the water structures, since the solvent relaxation time (tauS) in the resin was much longer than that in water and depended on p; tauS increased from 34 to 55 ps with increasing rho from 2 to 8%. The origin of the rho dependence of tauS was discussed in terms of the separation distance between the ion-exchange groups, and the effects of the counterion of the ion-exchange group on the solvation processes were also discussed. PMID- 11199992 TI - A compactly integrated flow cell with a chemiluminescent FIA system for determining lactate concentration in serum. AB - We have fabricated an integrated flow cell as a total microanalysis system (microTAS). This flow cell (size, 15 x 20 mm; total inner volume, 12.2 microL) was designed for a rational analyzing system of lactate determination for serum. This cell was made by micromachining techniques and consisted of two hollows of a lactate oxidase (LOD) reactor and a mixing cell, a spiral groove, and three penetrated holes. To form the reactor and capillary, these patterns, etched on a silicon wafer, were attached to a glass plate by the anodic bonding method. A photodiode was put under part of the spiral capillary. The compactly accumulated devices were integrated into a flow injection analysis (FIA) system. In the flow cell, lactate was catalyzed to pyruvate and hydrogen peroxide at the LOD reactor; subsequently, hydrogen peroxide reacted with the luminol-ferricyanic reagent at the mixing cell. The resulting chemiluminescent light was detected by the photodiode. Using the miniaturized flow cell, the sample volume for one measurement was greatly reduced to 0.2 microL. The response to lactate was obtained within 30 s and was linear between 0.5 and 5.0 mM (4.5 and 45 mg/dL) lactate with excellent correlative variances of 3.2% (average of three measurements at 5.0 mM). For practical application, the lactate concentration in control human serum was determined using this system. The results showed a good correlation coefficient (r = 0.979) with the results obtained by the spectrophotometric reference method. No difference in sera (normal or pathological) was found. Consequently, this integrated flow cell shows potential as a clinical device for lactate determination in serum. In this article, the effect of the design on the chemiluminescent FIA system is also described. PMID- 11199993 TI - A comparison of liquid hydrocarbon calibration standards in piston cylinders and standard cylinders with eductor tubes. AB - Natural gas liquid standards consist of various components primarily in the C1-C6 range; they are available in three types of cylinder packages: piston cylinders and two other types of standard cylinders with eductor tubes. The three cylinder packages have different operation conditions and thus a sample may behave differently in each of the packages. The piston cylinder maintains the components in a single liquid phase at a constant pressure, while the standard cylinders maintain the components as a two-phase mixture. Typically, the components may distribute between the two phases in different concentrations depending on the various thermodynamic variables, such as temperature, pressure, and volume. This study will examine the integrity of the sample in the three cylinder packages during a controlled cylinder depletion. The results for the various cylinders will be compared with a theoretical model of the experiments. PMID- 11199994 TI - Screening metal binding selectivities of macrocycle mixtures by HPLC--ESI-MS and postcolumn reactions. AB - A rapid method for the screening of metal binding selectivities of host compounds in mixtures is presented. This method involves the separation of mixtures of hosts by HPLC, followed by postcolumn complexation with one or more metals, then analysis by mass spectrometry. The intensities of the host-guest complexes in the mass spectra correlate with the binding selectivities of the hosts. The method was applied to a series of lariat ethers that were synthesized as ion-selective reagents for ion-selective electrodes. The compounds most selective for Na+ vs Li+ and K+ were identified. Additionally, a mixture of substituted calixarenes was screened for alkali-metal-binding selectivity. These compounds were determined to be selective for Cs+ over Rb+, K+, and Na+. PMID- 11199995 TI - [Stomach cancer: old and new problems]. PMID- 11199996 TI - [Descending perineum syndrome: iatrogenic or spontaneous pathology?]. AB - Among the causes of constipation, there is an infrequently recognised condition called descending perineum syndrome. This pelvic floor dysfunction causes a rectal tone disorder, and the clinical features include excessive and frequent straining and incomplete evacuation. Electrophysiological studies have shown a pelvic neuropathy in incontinent patients with descending perineum. The aetiological agents have been identified as follows: greater parity, dystocias and obstinate constipation, particularly if caused by expulsion difficulty. It has been observed that pelvic floor surgery may have physiopathological consequences that bring on the onset of dynamic disorders. The diagnosis may present difficulties and failure to identify the syndrome leads to inadequate and repetitive treatment of no real benefit to the patient. Since it is impossible to correct the excessive descent of the pelvic floor, the treatment will be aimed at resolving the predominant symptom in relation to the physiopathological factors causing it. PMID- 11199997 TI - [Therapeutic strategy in symptomatic diverticular disease of the colon]. AB - Diverticular disease of the colon has been recorded with increasing frequency and approximately 25-30% of symptomatic patients require surgery for complications. Controversy still surrounds the best operative approach for the management of diverticular disease, particularly when it presents with complications. The three stage operation has, for the most part, been abandoned because of its unacceptably high morbidity and mortality rates. Today it is generally believed that performing two-stage surgery is a wise decision, namely segmentary resection either without (Hartmann's procedure) or with anastomosis, protected by a covering colostomy. However, the ideal intervention is a one-stage surgical procedure (segmentary resection and primary anastomosis without a covering colostomy), but this can only be performed in selected patients. The aim of this study was to analyse the clinical course and the medical and surgical therapy retrospectively in 79 patients with symptomatic diverticular disease in order to identify the best therapeutic procedure; specifically, the severity of septic complications was evaluated using Hinchey's classification. The authors conclude that most patients with symptomatic diverticular disease require specific medical therapy. If surgical treatment is necessary (complicated diverticular disease), Hartmann's procedure is still a valid surgical option, particularly in the presence of diffuse faecal peritonitis. Colonic resection and primary anastomosis are certainly a satisfactory treatment, because of their low morbidity and mortality rates, but this surgical approach is only feasible in selected patients. Finally, it is a matter for the individual surgeon's experience to select the best surgical procedure in any particular situation, depending on age and general state, local findings and the extent of peritonitis. PMID- 11199998 TI - Primary breast carcinoma: immunocytochemical and immunohistochemical evaluation of biological parameters. AB - Fine needle aspiration biopsy is an effective procedure for the diagnosis and biological characterization of carcinoma of the breast. The authors compared the immunocytochemical expression of oestrogen receptor and progesterone receptor, Ki67 antigen and p53 protein, evaluated in pre-surgical fine needle aspirates, with the immunohistochemical results observed in the corresponding histological sections. Fine needle aspirates and paraffin embedded sections obtained from 37 patients with primary carcinoma of the breast were studied by immunocytochemistry and immunohistochemistry, respectively. Percentage agreement between values obtained with cytology and histology was 89.6% for oestrogen receptor, 76.9% for progesterone receptor, 91.3% for Ki67 and 77.7% for p53. The data reported here suggest that the evaluation of biological parameters by fine needle aspiration biopsy may be useful to decide the best medical and surgical treatment for primary breast carcinoma. PMID- 11199999 TI - [Clinical evolution of chronic pancreatitis and quality of life]. AB - Nowadays the availability of reliable, efficacious methods of assessing the outcome of chronic pancreatitis is mandatory, especially in view of the several new procedures developed to relieve the symptoms of the disease. Together with the traditional evaluation of postoperative morbidity and mortality and the assessment of exo/endocrine function in patient follow-up, we currently consider the patient's perception of his or her health status as a priority. This information is obtained by administering quality of life questionnaires along with reliable physical and psychometric evaluation. PMID- 11200000 TI - [Videolaparoscopy and carcinoma of the gallbladder]. AB - There have been several reports claiming that there is a risk that laparoscopic cholecystectomy might worsen the prognosis of unexpected gallbladder cancer. The objective of this study was to evaluate which factors influence the prognosis of such cancers. A clinicopathological study was conducted in 25 patients with unexpected gallbladder cancer. The results of 10 patients undergoing laparoscopic cholecystectomy were compared with those of 15 patients undergoing open cholecystectomy. Correlations were evaluated between cumulative survival rates and seven prognostic factors, namely, age, sex, histopathological grade, pathological stage, occurrence of bile spillage, type of cholecystectomy (laparoscopic or open) and additional surgical treatments. Seven patients after laparoscopic cholecystectomy (70%) and 9 patients after open cholecystectomy (64%) had cancer recurrence: the difference was not statistically significant. There was a statistically significant correlation between survival rate and tumour stage (P < 0.01) and occurrence of bile spillage (P < 0.05). There was no difference in survival depending on whether cholecystectomy was carried out using laparoscopic or traditional techniques. Laparoscopic cholecystectomy does not adversely affect the prognosis of unexpected gallbladder cancer. Once the histological findings have been examined, the surgeon will decide whether it is necessary to extend surgery, regardless of whether laparoscopic or open cholecystectomy is carried out. PMID- 11200002 TI - [Laparoscopic approach to inguinal hernia pathology]. AB - Laparoscopic hernia repair has already become as accepted a technique as the conventional ones and is routinely used in those centres where this kind of surgery is normally performed. The two most commonly used laparoscopic techniques (transabdominal and total extraperitoneal) have been shown to produce good results in terms of post-operative course and recurrence rates, but still present the disadvantages of high cost and the need for general anaesthesia. We report here a retrospective analysis of our early experience with laparoscopic treatment of inguino-crural hernias. The positive results achieved (no cases of conversion to an open technique; no recurrences to date; 4.7% major morbidity) allow us to consider this approach a valid alternative to the traditional ones in selected, well-informed patients. PMID- 11200001 TI - [Laparoscopic surgical treatment of cholecysto-choledochal calculi. A single step solution]. AB - The laparoscopic era has created a new basis for the management of choledocholithiasis. Many surgeons now regard laparoscopic cholecystectomy and exploration of the common bile duct as the "gold standard". The main advantages of single-stage treatment consist in a significantly shorter hospital stay, very low complication rates and a reduction of average hospital costs. Among 601 cases of cholelithiasis treated over the period from 1994 to 1999, we report 73 cases of common-bile-duct stones. Surgical sphincterotomy was performed in 20 cases and endoscopic sphincterotomy in 24; only in 7 cases was choledochotomy and/or hepaticojejunostomy (3 cases) performed for critical situations. Twenty-two cases of cholelithiasis were treated by laparoscopic cholecystectomy and exploration of the common bile duct. Stone extraction was obtained with a balloon catheter or Dormia basket via a choledochotomy. Surgery was completed by suturing, cholangiography and the placement of sub-hepatic drainages. No mortality or long term complications were recorded with the laparoscopic procedure; only two immediate complications were reported, both of which were biliary leakages (9%) that resolved spontaneously. With the other procedures, high rates of mortality, morbidity, hospital admissions and technical failure were registered. We regard laparoscopic exploration of the common bile duct as the treatment of choice for bile-duct stones when combined with cholecystectomy. We reserve ERCP plus endoscopic sphincterotomy only for common-bile-duct stones alone, without a gallbladder or gallstones. Open surgery is performed in particular situations such as Mirizzi's syndrome or when other procedures have failed to yield satisfactory results. PMID- 11200003 TI - [Surgery of the carotid artery: locoregional anesthesia versus general anesthesia: Review of the literature]. AB - The aim of the study was to compare locoregional and general anesthesia in carotid artery surgery in order to establish whether differences exist in terms of perioperative results, use of intraoperative shunts and costs. Seventeen studies, comprising 14,776 carotid endarterectomies performed with either locoregional or general anesthetic and published over the period from 1990 to March 2000, were reviewed. There were no statistically significant differences in the cardiovascular risk factors of the patients. Neurological morbidity and mortality were similar in the two groups, even if the use of shunts in the locoregional anesthesia group was lower than in the general anesthesia group and in four studies was associated with a significant difference (P < 0.01). No statistical differences in cardiac morbidity or mortality were found between the groups, except in two studies. Additional randomised prospective trials are needed in large numbers of patients. Locoregional anesthesia appears to allow a limited use of intraoperative shunts, but with neurological mortality and stroke rates very similar to those in the general anesthesia group. Routine use of locoregional anesthesia makes it possible to lower the cost of carotid surgery without sacrificing quality. PMID- 11200004 TI - [Anesthesia for inguinal hernioplasty: a comparison of techniques]. AB - New surgical and modern anaesthesia techniques for inguinal hernioplasty have significantly reduced the duration of the procedure and the postoperative length of hospital stay. From 1994 to 1998, 405 patients with a mean age of 54.7 years (range: from 18 to 90) undergoing inguinal hernioplasty were studied. Four different anaesthetic techniques were used: (i) surgical field infiltration (SFI) with 0.5% carbonated lidocaine + 0.125% bupivacaine (193 pts.) in which monitored anaesthesia care was administered with propofol (3 to 4 mg/kg/h) when necessary; (ii) epidural anaesthesia with 2% lidocaine + fentanyl 100 mg (137 pts.); (iii) general anesthesia with isoflurane and fentanyl in N2O:O2 (48 pts.); and (iv) intrathecal anaesthesia with 1% hyperbaric bupivacaine 1-2 ml (25 pts.). Intra- and postoperative complications, intraoperative sedation, postoperative supplemental drugs for analgesia and postoperative length of hospital stay were recorded. The data obtained were analyzed statistically using Student's t-test Anova, Bonferroni post hoc analysis, chi square, and P values less than 0.05 were considered significant. Intraoperative hypotension/brachycardia were observed in 4 patients (2%) in the SFI group and in 6 patients (4%) in the epidural group. Sedation was required in 29.5% of patients in the SFI group and in 15.3% in the epidural group (P < 0.05). Postoperative supplemental analgesic drugs administered and length of hospital stay were similar in the 4 groups. No difference in intra- and postoperative complications was observed among the 4 groups. Patients who required sedation in the SFI group were significantly more numerous than those with epidural anaesthesia. In conclusion, both SFI and epidural anaesthesia are safe and suitable for the inguinal hernioplasty procedure, without intra- or postoperative complications. PMID- 11200005 TI - Stress of routine follow-up in colorectal cancer operated patients. AB - Postoperative follow-up is the logical consequence of cancer treatment, but colorectal cancer follow-up does not achieve all its goals. These unfavourable findings induced us to assess whether follow-up also causes negative psychological stress in our colorectal cancer patients. In this trial 100 colorectal cancer follow-up patients were asked to compile three questionnaires: 1) the McGil Pain Questionnaires; 2) Profile of Mood Status; and 3) Locus of Control. The questionnaires were handed to the patients at follow-up and were compiled immediately. In addition, the patients were asked to answer the firsts two tests spontaneously 30 days after follow-up and mail the questionnaires. Our results showed that only 41% of the patients complied the tests 30 days after follow-up. The scores for pain and mood disorders were greater in women, especially during the "before follow-up" period. The third test revealed a prevalence of subjects with internal-type reinforcement. Our data revealed that: 1) patients tend to repress the problem; 2) women are affected by greater stress and anxiety; 3) subjects with internal-type reinforcement have a positive attitude during follow-up and this enables the ego to bear the anguish, process it and dilute it to anxiety, thus favouring future life experiences. PMID- 11200006 TI - Haemostatic treatment of a bleeding hepatocarcinoma by polypropylene mesh wrapping in a cirrhotic patient. AB - Spontaneous rupture of hepatocarcinoma (HCC) in a cirrhotic patient is a serious complication with a high incidence of mortality. The pathogenesis of this complication is unknown. Several hypotheses have been proposed in the literature worldwide. The diagnosis, in the absence of specific symptoms, is made by ultrasound, sometimes followed by a CT scan, and finally by exploratory paracentesis. An angiogram is performed to locate the site of the bleeding and possibly allow transcatheter arterial chemo-embolisation. Therapeutic options include one-stage or delayed resection, packing for sub-diaphragmatic bleeding HCC's, and hepatic artery ligation. Suture ligation of the bleeding source is usually impossible due to the friability of the tumor. No sizeable experience with the use of alcoholisation for haemostasis has been reported to date. We report a case of HCC bleeding from segment VI successfully treated by manual compression and placement of a polypropylene mesh (Biomesh P1, Cousin Biotech). PMID- 11200007 TI - Brunner's adenoma, esophageal reflux and gastric ulcer. A case report. AB - In this work the authors report a clinical case of Brunner's adenoma, which was responsible for the onset of other pathologies in the upper gastrointestinal tract, such as gastroesophageal reflux (GER), esophagitis and ulcerations of the antral mucosa. The preoperative diagnostic procedure (endoscopy, esophageal manometry, gastric emptying) and the follow-up at 3, 6 and 12 months from the surgery confirmed the relationship between the Brunner's adenoma and the alterations of the lower esophageal sphyncter (LES) tone and the gastric emptying. After a review of the international literature and a short analysis of the physiopathologic alterations, the authors point out the different therapeutical approach, in according to the size and implantation (sessile or peduncolated) of the lesion and to the related pathologies. PMID- 11200008 TI - [Inverted papilloma of the bladder: observation of 3 clinical cases and discussion on their clinico-pathologic characteristics]. AB - Three cases of urothelial inverted papilloma, detected in two female patients aged 32 and 31 years, respectively and in one 67-year-old male patient, are described. Inverted papilloma is a benign lesion which occurs in the urinary epithelium with a 20% incidence in comparison with other urothelial tumours. The male:female ratio is 3:1. The histological structure of urothelial inverted papilloma is similar to that of inverted papilloma of the nasal and paranasal sinuses. It presents interanastomosed epithelial cords, with transitional cells, which develop in the tunica propria connective tissue. Some cells are distributed in such a way as to constitute vacuolated glandular-like structures. The histogenetic origin of the lesion from Home subtrigonal or Albarran subcervical glands is debatable. Recent aetiological hypotheses have claimed that the origin of the lesion may be related to Brunn's nest hyperplasia and/or to chronic urothelial inflammation. The latter hypothesis would currently appear to be the most accredited: immunostaining for cytokeratins would tend to support a urothelial inflammatory aetiology. In our cases, we achieved a definitive diagnosis of inverted papilloma only at histology, because of the specificity of the echotomography and cystoscopy findings. Urinary cytology revealed only a large number of inflammatory cells with anaplastic elements, but without any more detailed morphological description. We performed a transurethral resection of the bladder (TURB) in all three patients: routine follow-up showed the absence of inverted papilloma relapses. On the basis of the above-mentioned data and a thorough review of the literature, we attempt to assess and classify the clinico pathological findings and the aetiological hypotheses of urothelial inverted papilloma. In addition, the benign nature of the lesion and any malignant transformation factors are discussed. PMID- 11200009 TI - [Sarcoidosis with a prevalent splenic localization: surgical option (presentation of a case]. AB - Sarcoidosis is a granulomatosis disease of unknown origin with a variable clinical presentation. The reported frequency of splenomegaly in sarcoidosis ranges from 1% to 40%. Splenomegaly has been associated with clinical evidence of more extensive thoracic and extrathoracic sarcoidosis. We describe an interesting case of sarcoidosis with giant splenomegaly and abdominal pain but no evidence of systemic involvement. Sarcoidosis must be considered in the differential diagnosis of splenomegaly. The main indication for splenectomy is splenomegaly with resulting discomfort and/or haematological abnormalities. Though the natural history of sarcoidosis is generally unchanged after splenectomy, in our patient the operation resolved the abdominal pain completely with no need for further therapy. PMID- 11200010 TI - [Thyroid metastasis of a renal carcinoma. 3 clinical cases]. AB - The clinical finding of metastasis to the thyroid is a very rare event. When a metastasis from a renal carcinoma is diagnosed, it is usually the distant evidence of a tumour discovered and removed surgically months or years before, or it may be the first clinical sign of an as yet undiagnosed asymptomatic renal tumour. A case of massive retrosternal goiter in a 65-year-old patient, operated on for a right renal carcinoma (nephrectomy 6 years before), is reported. The goiter, causing compression symptoms and dyspnoea, was treated by total thyroidectomy. The pathological diagnosis was metastasis from renal carcinoma. The authors present a second case of nodular goiter, in a 79-year-old woman, 9 years after a right nephrectomy for a renal carcinoma. The expanding nodule, diagnosed intraoperatively as carcinoma, was treated by total thyroidectomy. The postoperative pathological diagnosis was metastasis from renal carcinoma. The authors report a third case of an expanding nodule of the thyroid, in a 65-year old patient, diagnosed intraoperatively as a metastasis from renal carcinoma, treated by right lobectomy and isthmusectomy. An abdominal CT scan revealed a renal asymptomatic tumor, treated by right nephrectomy. The diagnosis can be established by means of fine needle aspiration biopsy preoperatively or intra- or postoperative histology. Surgical therapy may resolve the compression symptoms and improve the prognosis. PMID- 11200011 TI - [Malignant stromal tumors of the duodenum. Report of a case]. AB - The Authors report a rare case of undifferentiated duodenal malignant stromal tumour in a 69-years-old man radically managed by pancreaticoduodenectomy and resection of a liver metastasis. Several preoperative tests were performed (barium meal, endoscopy, ultrasonography and CT scan) but failed to yield a differential diagnosis between a tumour of the pancreatic head and a retroperitoneal neoplasm. The diagnosis was only histological. The tumour was considered to be high-grade due to its large size, high mitotic index, and the presence of necrosis and liver metastasis. Thorough surveillance revealed several hepatic metastases 29 months after resection, and chemotherapy performed at this stage proved completely ineffective. The patient died 38 months after surgery. PMID- 11200012 TI - [Postectomy for phimosis: 5-year-experience]. AB - Phimosis, i.e. congenital or acquired preputial stenosis, is one of the most frequent problems encountered in surgery departments. Circumcision remains the most frequently adopted surgical treatment, but, since this operation entails the sacrifice of the prepuce and frenulum, the penis loses its natural protection. The Authors describe five years of experience with postectomy, a technique which spares both the prepuce and frenulum while repairing the preputial phimosis, defining its benefits compared with circumcision. PMID- 11200013 TI - A comparison of performance of three gamma camera systems for positron emission tomography. AB - The development of coincidence positron imaging using a gamma camera should significantly increase PET utilization. This study has compared the performance of three such systems with each other and with an equivalent single photon emission computed tomography (SPECT) measurement. A Carlson phantom, which consisted of a 20 cm diameter cylinder containing areas of uniform activity, hot lesions, cold lesions and orthogonal alternate hot and cold lines, was filled with an activity of 18F chosen to try and best exploit each camera and imaged for a fixed time (27 min). The image quality of 9 mm thick slices in each section of the phantom was compared visually. Several image quality parameters were also compared including line source resolution and noise equivalent count rate. There were considerable differences in PET image quality between the three cameras but all were at least as good as the SPECT image. The full width at half maximum (FWHM) resolution of all systems was similar (approximately 4.5 mm) but the maximum noise equivalent count rates in a 20 cm cylinder were significantly different (6.3, 2.6 and 1.6 kcps) (where cps is counts per second) and correlated with the phantom image quality. PMID- 11200014 TI - 99Tc(m)-ECD SPET perfusion changes by internal pallidum stimulation in Parkinson's disease. AB - High-frequency stimulation of the internal pallidum is an effective surgical approach for patients with advanced Parkinson's disease suffering from motor fluctuations and L-dopa induced dyskinesia. To study the acute effects of internal pallidum stimulation, changes in cerebral blood flow were measured by means of a single-day split-dose protocol using 99Tc(m)-ECD SPET. Nine patients with advanced Parkinson's disease and with a clinical picture predominated by tremor and drug-induced dyskinesia, were imaged before and immediately after electrostimulation. Brain perfusion data were mirrored to the same electrode side (five left and four right implants), co-registered and analysed statistically on a voxel-by-voxel basis (Statistical Parametric Mapping) and by an automated volume-of-interest approach. Acute stimulation of the internal pallidum induced a significantly decreased perfusion in the ipsilateral thalamus and striatum, as well as in the right parietal cortex. For the subgroup of seven patients with effective motor score improvements, a significant correlation between thalamic and striatal perfusion changes and UPDRS III motor score was present (P = 0.04). These results suggest that effective stimulation of the internal globus pallidus may produce symptom relief through decreased activity in pallido-thalamo-cortical circuits. PMID- 11200015 TI - Regional cerebral blood flow in schizophrenia before and after neuroleptic medication. AB - In order to investigate cerebral perfusion changes induced by neuroleptic drugs, we performed 99Tc(m) hexamethyl propyleneamine oxime (HMPAO) single-photon emission computed tomography (SPET). Fifteen patients (nine drug naive, six non naive) diagnosed by using the DSM-III-R criteria, and 10 right-handed age and sex matched normal volunteers were included in this study. The SPET study was performed with 740 MBq 99Tc(m)-HMPAO by using a 128 x 128 matrix, 30 s/frame for a total 64 view over 360 degrees before and after 1 month of neuroleptic treatment. A semiquantitative method was used for the analysis. Patients were clinically assessed using the Brief Psychiatric Rating Scale (BPRS). There was no significant regional cerebral blood flow (rCBF) difference between the patient group and control group in whole-brain regions except in the left temporal lobe. Although clinical scores of the patients improved after neuroleptic treatment no statistically significant difference was found in the rCBF between pre- and post treatment. Moreover, there was no statistically significant correlation between the rCBF and BPRS in any region. These results suggest that there was a discrepancy between the clinical situation and rCBF in schizophrenia and the lateralized temporal lobe blood flow, which may have important implications for the evaluation of patients with schizophrenia. PMID- 11200016 TI - Diffuse cortical reduction of neuronal activity in unipolar major depression: a retrospective analysis of 337 patients and 321 controls. AB - Reduction of neuronal activity in frontocortical and limbic circuits is considered a characteristic of depression. We aimed to test this hypothesis by pooling all available data from experimental literature. All investigations were included comparing regional cerebral blood flow (rCBF) or glucose metabolism (rCMRGlc) between acutely depressed unipolar major depressive patients and healthy controls. For cortical and subcortical regions we computed the percentage difference between depressives (n = 337) and controls (n = 321). In patients with unipolar major depression rCBF and rCMRGlc were lowered in left (-4.4%, P = 0.022) and right frontal (-3.2%, P = 0.053), left (-1.7%, P = 0.061) and right temporal (-3.0%, P=0.003), left (-6.5%, P = 0.002), and right parietal (-8.8%, P=0.001), and left (-6.6%, P = 0.083) and right occipital cortex (-4.2%, P = 0.02). Moreover, there were reductions in left (-6.3%, P = 0.029) and right basal ganglia (-4.8%, P = 0.002), left (-3.4%, P = 0.114) and right thalamus (-3.1%, P = 0.036), and left limbic system (-2.2%, P = 0.127). Parameters were increased by 1.0% (P = 0.714) only in the right limbic system. There were no hemispheric asymmetries (P > 0.05). Moreover, there was no indication for an anterior posterior gradient (P > 0.05), and thus no 'hypofrontality'. In contrast to the current view, the data indicate a diffuse cortical rather than regionalized reduction of neuronal activity in unipolar major depression. PMID- 11200017 TI - Reproducibility of assessment of myocardial function using gated 99Tc(m)-MIBI SPECT and quantitative software. AB - PURPOSE: We investigated the reproducibility of the quantification of left ventricular volumes and ejection fraction, and grading of myocardial wall motion and systolic thickening with gated myocardial single-photon emission computed tomography (SPECT) and Cedars quantification software. PATIENTS, MATERIALS AND METHODS: We performed post-stress gated myocardial SPECT in 33 consecutive patients twice sequentially in situ. Sixteen frames per cycle were used for gating. Using Cedars quantitative gated SPECT software ventricular volumes and ejection fraction (EF) were calculated. Wall motion and thickening was graded using 5- and 4-point scores, respectively. Coefficients of variation for re examination of volumes and EF were calculated. Kappa values for assessing reproducibility of wall motion or wall thickening were calculated. RESULTS: Root mean square of errors was 5.0 ml for end-diastolic volume, 3.9 ml for end systolic volume and 1.9% for EF. No bias or difference was found between the first and second acquisition by Bland-Altman analysis. Kappa values for wall motion and thickening of repeated acquisition was 0.76 and 0.87, respectively. The value of 2 SD from Bland-Altman analysis was 14.4 ml for EDV, 11.2 ml for ESV and 5.3% for EF. CONCLUSION: We conclude that quantification of functional indices and assessment of wall motion or thickening using gated 99Tc(m)-sestamibi (MIBI) SPECT was reproducible and we found that their ranges of physiological fluctuation were narrow enough. PMID- 11200019 TI - Quantitative gated SPECT myocardial perfusion imaging with 201Tl: an assessment of the limitations. AB - Gated SPECT (GSPECT) perfusion imaging has been increasing in popularity both with 99Tc(m) agents and 201Tl. However, both higher activities than administered in the UK and multi-headed cameras are often used. The aim of this study was to assess GSPECT imaging using lower activities of 201Tl with a single-headed camera. Seventy patients underwent stress and redistribution GSPECT imaging after a mean injected activity of 62 +/- 7 MBq 201Tl. These patients also underwent radionuclide ventriculography (RNVG) imaging. The Cedars Sinai Quantitative Gated SPECT (QGS) package was used to calculate left ventricular ejection fraction (LVEF) from the GSPECT studies. Comparison of ejection fractions calculated using GSPECT with those calculated using RNVG yielded a correlation coefficient of 0.70 for the stress studies and 0.71 for the redistribution studies. The width of the mean 95% prediction interval ranged from 22 to 74 percentage points for the stress studies and 22 to 86 percentage points for the redistribution studies. Ejection fractions calculated from stress and redistribution GSPECT studies showed a correlation of 0.80 with a mean 95% prediction interval of 42.6 +/- 0.4 percentage points. In conclusion, left ventricular ejection fractions calculated using the QGS algorithm from 201Tl GSPECT studies are inadequate for use in clinical practice. PMID- 11200018 TI - Three-dimensional automatic image warping in cardiac SPECT. AB - This study presents a new tool for the visualization and analysis of three dimensional (3-D) cardiac single-photon emission computed tomography (SPECT). The first step consisted of computing the 3-D pseudo-skeleton of a binarized myocardium and, using the skeleton points, to design a bullet model (half ellipsoid prolonged by a cylinder). Afterwards, this model was used to drive the warping of the 3-D myocardium, initially egg-shaped, into a thick, flat disc using the thin-plate splines as deformation method. Hence, instead of achieving several rotations of the initial egg-shaped volume to have an idea on the myocardial outer face (epicardial) only, the whole myocardium is seen by looking either on top of the disc-shaped transformed myocardium (epicardial surface) or underneath for the inner face (endocardial). This new shape permitted us to localize any type of defect and to evaluate its extent and depth just by a single glance. A detailed analysis, achieved after stripping away this shape in about 10 layers, allowed us to evaluate the defect extent layer by layer and to determine whether the defect involves the totality of the myocardium layers. Finally, its flattening following the ventricular long-axis led to a summed bull's eye. PMID- 11200020 TI - Estimation of ascitic fluid volume using 99Tcm labelled macroaggregated albumin. AB - We have assessed the usefulness of a radionuclide dilution method for estimation of ascitic fluid volume. 99Tc(m) macroaggregated albumin (10 MBq) was injected into the peritoneal fluid. Multiple samples were taken using a trocath peritoneal dialysis catheter over a 4-h period. Blood samples were taken at the same time and a 4-h urine collection was made during the study. At 4 h a controlled drainage of ascitic fluid, followed by suction drainage, was used and a total drained volume measured. For comparison, peritoneal volumes were measured from the radioactivity of peritoneal fluid activity samples using dilution techniques. The estimated peritoneal fluid volume using the radionuclide method was consistently higher than the drained volume. This was attributed to either a lack of uniform distribution of the activity in the peritoneal cavity by 4 h or early breakdown and absorption of activity from the peritoneal cavity. In two patients it was not possible to measure a volume due to poor distribution of the radionuclide in the peritoneal fluid. We found that in our group of patients the radionuclide dilution is of little value in estimating the peritoneal fluid volume. PMID- 11200021 TI - Plasma clearance of 99Tc(m)-MAG3: accuracy of five single-sample methods. PMID- 11200022 TI - How good is the slope on the second exponential for estimating 51Cr-EDTA renal clearance? A Monte Carlo simulation. PMID- 11200023 TI - Rethinking risk. PMID- 11200024 TI - "On a supposed right to lie [to the public] from benevolent motives": communicating health risks to the public. AB - There are three main categories of rationale for withholding information or telling lies: if overwhelming harm can only be averted through deceit; complete triviality such that it is irrelevant whether the truth is told; a duty to protect the interests of others. Public health authorities are frequently having to form judgements about the public interest, whether to release information or issue warnings. In June 1992, routine surveillance detected patulin levels (a known carcinogen) in samples of apple juice exceeding safety threshold. Remedial actions were promptly taken and it was planned to subsequently publish the information in the routine way. However, the media portrayed the handling of the problem as a conspiracy and there was a short term reduction in juice sales. In October 1995, the UK Committee on Safety of Medicines issued a warning about certain brands of the contraceptive pill, based on the interim results of three unpublished studies. The increased risk of thromboembolism was small, but the resulting scare led to an increase in unwanted pregnancies. The handling of the B.S.E. crisis in the U.K. also led to accusations of incompetence or conspiracy. Public health authorities have to handle uncertainty and frequently have to form judgements for public safety on the basis of evidence of poor quantity and quality. Their task is not helped by the sometimes conflicting agenda of scientists and media. The public also have differing perceptions and interpretations of risk. The series of scares and crises are having a detrimental effect on public confidence in public health authorities. PMID- 11200025 TI - Health risks and the health care professional. AB - Health care professionals are one of a large group of individuals who are exposed to significant risks by virtue of their occupation, such as the police, mountain rescuers, fire-service. The types of risk to which health care professionals are exposed are numerous, many of which remain largely unrecognised by the public and may even be underestimated by the professionals themselves. Examples of these health risks include fatigue, emotional/psychological trauma, physical injury caused by the use of machinery, back injuries, possible even violent physical assault from a patient or hospital visitor. There is also a very significant risk of acquiring an illness in the course of employment, for example, physical damage caused by the prolonged use of toxic substances, and also infectious diseases which are acquired by various routes, such as air-borne infections, needle-stick injuries. Subjective risk evaluation and the notion of risk in health care from the patients' perspective has been widely considered over many years, and in a number of different areas, including medical research, screening procedures, consent to surgery or other medical intervention. In this paper, however, the moral dilemmas which may arise for health care professionals in relation to health risks are highlighted and specific questions are raised. PMID- 11200026 TI - From risk factors to health resources in medical practice. AB - The healing and preventive powers of people's health resources and self-assessed knowledge have so far been grossly underestimated in medicine. In this article, we call attention to ethical and epistemological dilemmas related to knowledge, values, communication, and autonomy embedded in the prevailing risk-oriented epidemiology, and suggest a patient-centred salutogenetic approach to promote a better balance between resources and risks in medicine. Identification and intervention upon risk factors can provide hypotheses about origins of disease and predict and sometimes prevent disease at a group level. However, there are several pitfalls related to this perspective concerning causal factors, group level based possibilities, adequate end points for intervention, informed consent, and medicalization, especially in the individualized context of the clinical encounter. By introducing a salutogenic perspective, we urge to shift the attention toward resources, agency and strength, which may counteract risk of disease and empower the patient. Talk can mediate oppression as well as empowerment. A communicative key question approach, and self-assessed health resources identified through this strategy, are briefly presented as examples of empowerment through dialogue. PMID- 11200027 TI - Power and hope in the clinical encounter: a meditation on vulnerability. AB - A specific clinical encounter in which the author was an ethics consultant, after a brief summary, provides the basis for a phenomenological delineation and explication of the key ingredients of such encounters. A brief historical reflection on the myths of Gyges and Aesculapius suggests that several of these ingredients are essential to clinical encounters and help constitute their specific moral aspects and challenges. Understood as an interpersonal relationship framed by critical issues of illness experiences, the clinical encounter makes prominent such constitutive features as dialogue, trust, violence, and especially vulnerability and power. The role of the clinical ethicist is found to be often critical in these encounters, in particular because of the need to help patients and doctors identify, understand, and cope productively with fundamental moral phenomena. PMID- 11200028 TI - Oliver Sacks--a neurologist explores the lifeworld. AB - The neurologist Oliver Sacks has become very famous for his writings. His popularity has scattered all mass medias. In his books, he eloquently tells stories about patients suffering from extraordinary neurological diseases. Since the conceptual framework of Sacks' narratives has been widely unconsidered, this article pursues a more general and systematic approach to his work. Sacks terms his idiographic and phenomenological access to the world of science Romantical Science. With its features, he develops a concept of a Neurology of Identity, that is basically concerned with the patient's personality and subjectivity. Sacks' personal approach to medicine implies another understanding of diseases: For him, diseases cannot be reduced to pathological facts, they constitute other worlds. He characteristically uses philosophical, psychological and mythical terms for interpretation and narration. But conversely to its sympathetic appearance, Sacks' approach entails some deficits: His presentation is not always realistic, his interpretations are often one-sided. The theoretical reflections on his method and attitude remain poor. Nevertheless, he puts medicine back into lifeworld, to open it for many discourse universes beyond science in practice and theoretical reflection. PMID- 11200029 TI - Teaching for patient-centred ethics. AB - In this paper three models of teaching and learning medical ethics are discussed critically, the traditional and revised vocational models, and the patient centred model. The autonomy-oriented patient-centred ethics of Beauchamp and Childress is rejected in favour of a hermeneutic practical ethics. A performative conception of ethics teaching is recommended as the most appropriate model for use in the theory and practice of ethics pedagogy. PMID- 11200030 TI - Expert and non-expert knowledge in medical practice. AB - One problematic aspect of the rationality of medical practice concerns the relation between expert knowledge and non-expert knowledge. In medical practice it is important to match medical knowledge with the self-knowledge of the individual patient. This paper tries to study the problem of such matching by describing a model for technological paradigms and comparing it with an ideal of technological rationality. The professionalised experts tend to base their decisions and actions mostly on medical knowledge while the rationality of medicine also involves just as important elements of the personal evaluation and knowledge of the patients. Since both types of knowledge are necessary for rational decisions, the gap between the expert and the non-expert has to be bridged in some way. A solution to the problem is suggested in terms of pluralism, with the patient as ultimate decision-maker. PMID- 11200031 TI - On how to define the concept of health: a loose comparative approach. PMID- 11200032 TI - On the comparative approach to defining health: a reply to Brulde. PMID- 11200033 TI - More on the looser comparative approach to defining "health": a reply to Nordenfelt's reply. PMID- 11200034 TI - Supracondylar fractures of the humerus in children. PMID- 11200035 TI - X-linked hypophosphatemic rickets--a report of 2 cases and review of literature. AB - We report two cases of x-linked dominant hypophosphatemic rickets involving a man and his daughter. The family tree consists of 44 members with 13 of them having short stature and bowing of the lower limbs. The study of this family tree strongly suggests an x-linked dominant inheritance. PMID- 11200036 TI - Tuberculosis of the distal end of the radius mimicking a giant-cell tumour. AB - We report a case of a lady presenting with a lesion in the distal radius with classical radiological features of a giant-cell tumour. These tumours are often resected without preliminary histological confirmation. A biopsy done in this patient showed it to be tuberculosis. PMID- 11200037 TI - Osteopoikilosis--a case report. AB - Osteopoikilosis is a rare, inheritable, sclerosing bone dysplasia; sometimes mistaken for osteoblastic bone metastases. We report a case in a 25 year-old lady. PMID- 11200038 TI - Thoracolumbar fracture--dislocation results of surgical treatment. AB - Fifteen cases of unstable fracture-dislocation of the thoracolumbar spine have been treated by open reduction, short segment transpedicular fixation and fusion in Universiti Unit, Kuala Lumpur Hospital from January 1994 until December 1997. Twelve male and three female patients were injured; their age ranged from 18 to 45 years. Five fracture-dislocations occurred in the lower thoracic spine (T8 to T11), eight at the thoracolumbar junction (T12 to L2) and two in the lumbar spine (L3 to L5). All the patients had neurological deficit. Seven patients with incomplete or cauda equina lesions regained some neural function, while all eight with complete lesions remained unchanged. Ten of the fifteen cases were grossly unstable and translated beyond 50% of the width of the spinal column. At the time of follow up (more than one year in all patients), no loss of reduction or of fixation was noted in any patient. Solid fusion was achieved in all patients. The advantages of this method of treatment include stable fixation, with maintenance of sagittal and coronal spinal alignments, to allow early rehabilitation. PMID- 11200039 TI - Spinal infection--an overview and the results of treatment. AB - A retrospective review of thirty-eight patients (16 males and 22 females) with spinal infection between 1993 and 1998 revealed that the mean age was 39.9 years and the peak incidence was in the 5th decade of life. Infections in thirty-two patients (84.2%) were tuberculous in origin, 13.2% were pyogenic and 2.6% were fungal. Back pain was a symptom in 94.7% while 55.8% had neurological deficits, of which two-thirds were tuberculous in origin. Twenty-two patients (57.9%) had an impaired immune status secondary to pulmonary either tuberculosis, diabetes mellitus, intravenous drug abuse, prolonged steroid treatment, malnutrition, or advanced age. History of contact with tuberculous patients was elicited in 31.3%, extraskeletal tuberculosis was found in 28.1%, while Mantoux test was only positive in 53.1% of tuberculous patients. Majority of the cases (57.9%) involved lumbar vertebra. The histopathological examination was only positive in 22.2% from material taken via CT guided biopsy but 93.3% were found to be conclusive from open biopsy. 4 out of 5 patients who had a pyogenic infection were treated conservatively and produced a good result. There was no difference in outcome for tuberculosis patients treated with either the 3 drug or 4 drug regimen. Anterior decompression and bone grafting in tuberculous patients was superior in terms of a faster fusion rate, early pain relief and prevention of kvphotic deformity. The initial neurological deficit did not reflect the future prognosis of patients with spinal infection. PMID- 11200040 TI - HUKM instrumentation system in surgical treatment of adolescent idiopathic scoliosis--an early experience. AB - Between May 1992 through October 1998, twenty-two patients who had adolescent idiopathic scoliosis were treated using Universiti Kebangsaan Malaysia (UKM) spinal instrumentation and fusion. The minimum length of follow-up was 2 years with an average of 2.9 years. Nineteen patients were female and three patients were male. The mean age at the time of the operation was 16.2 years (range, 13 to 24 years). The average blood loss was 1,878 ml and the average operating time was 291 minutes. The mean pre-operative curve was 61.2 degrees, with a range of 40 degrees to 90 degrees. The average post-operative correction of the Cobb's angle was 53.5 per cent, with a range of 33 per cent to 81 per cent. Post-operative immobilization consisted of a maximum of six months in a body cast. There were no neurological injuries, no deep wound infections, and no evidence of pseudoarthroses. Only three complications occurred and these did not disturb the progress of the fusion. This technique safely achieves the objectives of scoliosis correction, and is cost-effective in the treatment of adolescent idiopathic scoliosis. PMID- 11200041 TI - Selective thoracic fusion of King II scoliosis with segmental spinal instrumentation. AB - Segmental spinal instrumentation with Harrington rod secured to the spine by sublaminar wires was a popular method of scoliosis correction in 1980's. It was gradually replaced by newer rod-hook systems due to concern about neurological complications. However, correction of type II and III curves by selectively fusing the thoracic curves with these new instruments has resulted in poor results in some cases. The aim of this study is to review the result of selective thoracic fusion treated by segmental spinal instrumentation. Between January 1989 to October 1994, 31 patients with King II scoliosis were treated operatively in our unit. These consisted of 29 girls and 2 boys. The mean age of these patients were 11.3 years. The study population consisted of 21 Chinese, 5 Malays and 5 Indians. In one patient, the thoracic curve was convex to the left whilst the thoracic curves in the majority were to the right. The surgery was performed by three surgeons using harrington rods and posterior fusion with autograft. Anterior releases were also required in eight patients to increase flexibility. The curve correction obtained was an improvement from a average preoperative cobb's angle of 71.5 degrees to 39.5 degrees postoperatively. After an average follow-up period of 77.9 months, the correction deteriorated by 22% in the thoracic curve and 59% in the lumbar spine without disturbance to truncal balance. Only one sublaminar wire broke. However, no implant failure or removal has to be performed as yet. This technique appears useful in our institution with minimal morbidity. PMID- 11200042 TI - Experience in snuffbox arteriovenous fistulae for hemodialysis. AB - Sixty-five patients with "Snuffbox" arteriovenous fistulae for hemodialysis were reviewed. The procedure was performed under local anaesthesia as an outpatient procedure. It was done as a "standby" procedure for 41.5% of patients with Chronic Ambulatory Peritoneal Dialysis. 58.5% of patients had the procedure done for primary hemodialysis. Patency was assessed as presence of an engorged vein and presence of thrill. This was assessed routinely at 4 to 6 weeks after the procedure. Patency rate was noted to be 83%. The commonest complication was thrombosis of the arteriovenous anastomosis. Some patients required repeated procedure at a more proximal site. Further study to determine the blood flow rate provided by the anastomosis, and comparison with other anatomical sites is necessary. PMID- 11200043 TI - Supracondylar fractures of the humerus in children--an epidemiological study of 132 consecutive cases. AB - 132 consecutive cases of supracondylar fractures of the humerus admitted between July, 1997 and February, 1999 were included in a prospective study. There were 93 boys and 39 girls. The age ranges from one to 14 years old. The non-dominant arm was more often injured. Ethnic Malay constituted the majority. Accidents mainly occurred at home with a peak between 4 pm and 8 pm. Majority was presented within 24 hours of injury. Type III fracture with distal fragment in extension predominated. Nerve injuries occurred in 9 cases in which median nerve was the most commonly affected. There was only one open fracture and it was complicated by absent radial pulse and median nerve injury. PMID- 11200044 TI - The results of open reduction and pin fixation in displaced supracondylar fractures of the humerus in children. AB - The treatment of displaced supracondylar fracture humerus (Gartland Type III) in children continues to be a challenging problem. We did a retrospective study of such fractures treated in Hospital Muar, over a 2 years period (from January 1998 to December 1999). A total of 42 cases with displaced supracondylar fractures, treated with open reduction and internal fixation were studied. All cases were operated using a posterior triceps splitting approach and crossed kirschner wires were used to stabilize the fracture site. An excellent outcome was seen in 34 patients (81%) and a good outcome in 7 patients (17%). The incidence of complications such as pin tract infection (14%), nerve injury (2%) was very low. None of the patients had vascular complications or myositis ossificans. PMID- 11200045 TI - Functional outcome of open reduction and internal fixation of pelvic ring injuries. AB - Between January 1996 and August 1998, 15 patients with pelvic ring injuries were treated by open reduction and internal fixation. Fractures types included Tile A1 (7%), B1 (33%), C1 (53%) and C3 (7%). The patients were observed for an average of 1 year (range: 5 to 21 months). Thirteen patients (87%) who were operated within 3 weeks after injury had their pelvic disruption healed. One patient with Tile C1 and non-union of the fracture dislocation of sacroiliac joint was operated 11 months after injury and developed implant failure and non-union of the fracture dislocation of sacroiliac joint. Another patient with Tile C1 injury with transforamina sacral fracture was fixed anteriorly only and developed non union of the sacral fracture and redisplacement of pelvic disruption. Both of them had a poor functional outcome. A 40 points pelvic outcome grading scale (Cole et al 1996) based on physical examination, pain, radiographic analysis and activity/work status was used. Six patients (40%) (1 Tile A1, 5 Tile B1) had an excellent functional outcome. Seven patients (47%) (6 Tile C1, 1 Tile C3) had a good functional outcome. PMID- 11200046 TI - Clinical experience with reamed locked nails for close and open comminuted tibial diaphyseal fractures: a review of 50 consecutive cases. AB - We present the results of our experience in treating comminuted tibial shaft fractures with reamed interlocking intramedullary nail from September 1993 to December 1995. In this retrospective study, there were fifty patients with an average follow-up of 14.3 months (range six to twenty-eight months). Ninety-eight percent of the fractures were due to motor-vehicle accident with majority of the patients being motorcyclist (96%). Thirty-eight fractures were closed and twelve were open (Gustilo grade I--8; grade II--4); 44% of them had additional fractures or other injuries. According to Winquist-Hansen classification of diaphyseal fracture comminution, there were 24% type I; 18% type II; 26% type III and 32% type IV. The union rate was 98%. There were 6 infections, 2 superficial and 4 deep. All these infections arose from closed fractures, which was possibly due to the long operative time. No patients with open fractures, which underwent delayed nailing, had infection. One of the patient had severe deep infection which required early nail removal before union. Anterior knee pain following nailing occurred in 6% of the patients. The average hospital stay after operation was 3.4 days. Ninety-four percent of the patients had excellent to good functional outcome after nailing. The mean time to regain full range of movement of knee and ankle was 8.4 weeks. Patients were allowed full weight bearing in the average time of 10.7 weeks and the mean time to return to work was 24.7 weeks. PMID- 11200047 TI - Proximal third femoral shaft fractures in children: prevention of angular deformities using bilateral Thomas splints. AB - This is a prospective study to look at the outcome of unilateral proximal third femoral shaft fractures in children treated with a bilateral Thomas splint in the Department of Orthopaedic Surgery Universiti Kebangsaan Malaysia between the period of January 1996 and June 1998. Eighteen children aged between 2 years and 12 years old with unilateral proximal third fractures of the femoral shaft were treated using a bilateral Thomas splint. Angular deformities were measured using a goniometer metric scale before and after Thomas splints. The percentage of varus tilt corrected ranged from 17% to 72% with an average correction of 29% from the initial deformity and the difference was statistically significant (p < 0.05). The percentage of posterior tilt corrected ranged from 19% to 60% with the average correction of 20% from the initial deformity. The difference was statistically significant (p < 0.05). From this study, we conclude that bilateral Thomas splints can give a better correction of angular deformity for proximal third femoral shaft fractures in children below twelve years of age. PMID- 11200048 TI - Total hip arthroplasty in Malaysia--the Universiti Kebangsaan Malaysia and Hospital Kuala Lumpur experience. AB - The results of 109 primary total hip arthroplasties in 92 patients performed in Hospital Kuala Lumpur from January 1987 to December 1996 were reviewed after a mean follow-up of 30.8 months. There were 22 males and 70 females with the average age of 49.9 years (range 19 to 94 years). Chinese females comprised the largest group of patients (52.2%). Avascular necrosis was the most common diagnosis (33.1%) followed by hip dysplasia and primary osteoarthritis (17.4%). The procedure was performed more on the right hip (64.2%) compared to the left (35.8%). All patients received prophylactic antibiotics but none were given deep vein thrombosis prophylaxis. The Charnley prosthesis was most commonly used and the majority of the arthroplasties were cemented (60.5%). About 80% of the THA were performed via the lateral approach. The functional hip score improved from an average of 8.9 to 15.0 with 66.3% of the patients categorized as good and excellent results. There were 16 patients (17.4%) with poor outcome. The most common complications encountered were dislocation (10.1%), aseptic loosening (9.2%) and periprosthetic fracture (5.5%). Other complications were deep infection (1.8%), deep vein thrombosis (0.9%), trochanteric osteotomy complications (1.8%), superficial infection (7.3%), urinary tract infection (5.5%), pressure sore (3.7%) and respiratory complication (1.8%). Fifteen hips (13.8%) required revision. The causes for revision were aseptic loosening, dislocation and infection. Technical anomalies were recognized as one of the factors contributing to poor results. Five-year survival rate was 87.3%. Better results can be expected with increasing experience and technical skulls. PMID- 11200049 TI - Limb reconstruction surgery with external fixators--university hospital experience. AB - We are describing 21 limb reconstruction procedures performed in 18 patients with the use of external fixators from 1996 to 1998. The average age of patients was 21, ranging from 1 to 50 years old. Indications for surgery included short limb, non-union, pseudoarthrosis and bone or soft tissue deformities. Average length obtained for cases of limb lengthening was 6 cm. All the seven clubfoot deformities in five children were fully corrected. Equinus deformity recurred in one foot and was treated with supramalleolar osteotomy. Out of the seven cases with infected nonunion and bone loss, three failed to achieve union and required additional bone grafting procedures. One patient with unilateral external fixator for the correction of tibia shortening developed valgus deformity. PMID- 11200050 TI - Short segment posterior instrumentation, reduction and fusion of unstable thoracolumbar burst fractures--a review of 26 cases. AB - From January 1994 to January 1998, 26 patients of unstable thoracolumbar burst fracture were treated by a short segment posterior instrumentation (pedicular screw plate/rod system), reduction and fusion in Kuala Lumpur and Universiti Kebangsaan Malaysia Hospital. Majority of them were young and in a productive age group (mean age were 30 year-old). The mean duration of follow-up was 24.4 months. The injuries were caused by fall from height (69%) and motor vehicle accident (31%). Most of the fracture occurred at 1st and 2nd lumbar vertebrae (24/26). Twelve of the patients did not have neurological deficits. Out of 14 patients with neurological deficits, 64.4% of them showed an improvement of at least one Frankel's grade. There was no defect correlation between canal compromise and neurological deficit. Kyphotic angle improved from 20 degrees to 7 degrees immediately after surgery. In the last follow-up average kyphotic angle was 9 degrees with average lost of 2 degrees. The average length of hospitalization following surgery was 24 days. A posterolateral bony fusion was achieved in all cases at an average of 3 months. Complication included 2 loosening and 3 misplacement of pedicle screw fixation. We concluded that short segment fixation with posterolateral decompression and fusion is effective in the treatment of unstable thoracolumbar burst fracture. PMID- 11200051 TI - Candida albicans infection of a prosthetic knee replacement: a case report. AB - We report a 64 year old man who developed Candida albicans infection following total knee arthroplasty. A two-stage exchange arthroplasty was performed after an initial swab culture grew Acinobacter sp. A scanty growth of yeast was also found from the tissue culture. Intravenous cefuroxime was instituted for six weeks followed by reimplantation four months after the removal. Three weeks after that revision, the prosthesis became infected and a culture of knee aspirate established the diagnosis of Candida albicans infection. Treatment consisted of thorough debridement of the involved joint and oral fluconazole for a year. Infection was never totally resolved and a secondary infection with methicillin resistant staphylococcus aureus then developed. Excision arthroplasty was done at two and a half years after the initial infection. At five years follow-up the infection was quiescent and he had a range of movement of 30 degrees to 70 degrees. Knee brace was used to control the valgus-varus stability. PMID- 11200052 TI - Neurological recovery in a patient with recurrent aggressive giant cell tumour of the axis--a case report. AB - A rare case of an aggressive recurrent giant cell tumour of axis is presented. The problems encountered in diagnosis and management are discussed. High dose dexamethasone was found to be useful managing this inoperable aggressive tumour which was compressing the cord. Early diagnosis would facilitate wide excision of the tumour with good prognosis. PMID- 11200054 TI - Heterogeneity of human peripheral blood monocyte subsets. AB - In recent years the number of reports describing phenotypically and functionally distinct subsets of human blood leukocytes, and in particular of subtypes of antigen-presenting cells has continuously increased. A great diversity was described not only for dendritic cells (DC), but also for human blood monocytes (Mo) and macrophages (Mac). Similar to DC, the different types of Mo subsets could be defined by distinct phenotypes and immunoregulatory functions. The characterization of blood Mo subpopulations revealed that some of them exhibit common features with myeloid or lymphoid DC and tissue Mac, but also demonstrate the existence of novel unique cell populations. The generation of lymphoid and myeloid DC and their heterogeneity has been the subject of recent reviews. Here we focus on Mo from human peripheral blood and summarize the data (including our own) dealing with their phenotypic and functional, in particular immunoregulatory properties. PMID- 11200053 TI - Pivotal role of 5-lipoxygenase in the activation of human eosinophils: platelet activating factor and interleukin-5 induce CD69 on eosinophils through the 5 lipoxygenase pathway. AB - CD69 is an activation-related cell surface molecule on human eosinophils. It has been reported that interleukin (IL)-5, but not platelet-activating factor (PAF), can induce CD69 on human eosinophils in vitro. In this study, PAF induced CD69 intensely on eosinophils from patients with hypereosinophilic syndrome (HES), while only weakly on those from normal donors. Because HES eosinophils contain abundant cytosolic phospholipase A2 (cPLA2) and 5-lipoxygenase (5-LO), we examined the roles of several enzymes involved in the metabolism of arachidonic acid in the PAF- or IL-5-induced CD69 expression on eosinophils. The CD69 expression induced by PAF and IL-5 on HES eosinophils and that by IL-5 on normal eosinophils were both inhibited by AA861 and MK-886, inhibitors of 5-LO activity. In addition, AACOCF3, a selective cPLA2 inhibitor, inhibited IL-5-induced CD69 expression on normal eosinophils, although it hardly affected either IL-5- or PAF induced CD69 expression on HES eosinophils. Moreover, PAF alone induced CD69 only weakly on normal eosinophils, but exogenous arachidonic acid remarkably enhanced PAF-induced CD69 expression on them. These findings suggest that IL-5 activates both cPLA2 and 5-LO but PAF activates only 5-LO. It is suggested that 5-LO plays a critical role in the induction of CD69 on eosinophils. PMID- 11200055 TI - Interleukin-12 can replace CD28-dependent T-cell costimulation during nonspecific cytotoxic T lymphocyte induction by anti-CD3 antibody. AB - Cytotoxic T lymphocyte (CTL) development is regulated closely by an intricate series of signals provided by the T-cell receptor/CD3 complex, cytokines, and costimulatory ligand/receptor systems. In this study, we have explored the role of interleukin (IL)-12 and CD28 in mouse CTL development. Activation of T cells with anti-CD3 monoclonal antibody (mAb) in the presence of anti-CD86 mAb, which prevents CD28-CD86 interaction, led to decreased production of type 1 (IL-2, interferon-gamma) and type 2 (IL-4, IL-6, IL-10) cytokines, as well as diminished expression of granzyme B (Gzm B) and reduced cytotoxic effector function. Cytolytic activity in T-cell cultures that were activated in the presence of anti CD86-blocking mAb alone or in combination with anti-CD80 mAb could be restored by the addition of exogenous IL-12 at initiation of culture. The ability of IL-12 to substitute for CD28-costimulatory signaling during CTL development was found to be dependent on the presence of IL-2 rather than interferon-gamma. IL-2 is required for IL-12Rbeta2 expression by T cells activated in the presence of anti CD86 mAb. Moreover, IL-12Rbeta2 expression by T cells activated in the presence of anti-CD86 mAb is enhanced by IL-12. We, therefore, conclude that the ability of IL-12 to substitute for CD28-costimulatory signaling during CTL development is a result of the interaction of IL-12 with IL-12Rbeta2 induced by low levels of IL 2 synthesized by T cells activated in a CD28-independent manner. PMID- 11200056 TI - Activated human platelets express Fas-L and induce apoptosis in Fas-positive tumor cells. AB - In addition to their role in hemostasis and thrombosis, platelets are important modulators of immune and inflammatory responses. We provide evidence here that human platelets contain abundant quantities of Fas-L, and upon activation, they express it on their surface as well as release it into medium. This surface expressed Fas-L is biologically active and can induce apoptosis in Fas-positive human tumor cells. Therefore, activated platelets may represent an important player in Fas/Fas-L-mediated apoptosis. PMID- 11200057 TI - Tumor cell-derived TGF-beta and IL-10 dysregulate paclitaxel-induced macrophage activation. AB - Paclitaxel (TAXOL) activates in vitro macrophage (Mo) expression of proinflammatory and cytotoxic mediators, including IL-12, tumor necrosis factor alpha (TNF-alpha), and nitric oxide (NO). However, tumors dysregulate Mo through soluble suppressor molecules, and it is possible that tumors evade paclitaxel mediated immune effector function through the production of immunomodulatory molecules and inhibition of Mo function in situ. Because Mo activation in the tumor microenviroment is a desirable goal of anti-tumor immunotherapy, we evaluated whether tumor-derived immunomodulatory factors dysregulate paclitaxel mediated Mo activation. Tumor cell-derived supernatant suppressed paclitaxel's capacity to induce IL-12, TNF-alpha, and NO production by RAW264.7 Mo. Tumor factors also dysregulated paclitaxel-induced expression of a HIV-LTR, promoter driven luciferase construct in RAW264.7 Mo, suggesting that tumors may inhibit a broad range of Mo functionality. Depletion studies revealed that IL-10 and transforming growth factor-beta1 (TGF-beta1), but not prostaglandin E2 (PGE2), impaired paclitaxel-mediated activation, suggesting that abrogation of these factors in situ might restore paclitaxel's activating capacity and enhance anti tumor efficacy. PMID- 11200058 TI - Impaired IL-15 production associated with susceptibility of murine AIDS to mycobacterial infection. AB - LP-BM5 murine leukemia virus (MuLV) injection causes murine AIDS (MAIDS), a disease characterized by many functional abnormalities of immunocompetent cells. We show that MAIDS mice are susceptible to Mycobacterium bovis Bacille Calmette Guerin (BCG) infection as assessed by survival rate and bacterial counts. The peritoneal exudate macrophages from MAIDS mice produced a significant level of interleukin (IL)-12 soon after inoculation with BCG, whereas IL-15 and tumor necrosis factor (TNF) production were severely impaired in BCG-infected MAIDS mice. The appearance of natural killer (NK) and CD4+ T helper type 1 (Th1) cells specific for mycobacterial antigen were depressed in MAIDS mice after BCG infection. Thus, it appeared that impaired production of IL-15, besides other inflammatory cytokines, in MAIDS mice may be involved in the poor responses of the NK and Th1 cells, resulting in an increased susceptibility to BCG. PMID- 11200059 TI - Autocrine action of IL-10 suppresses proinflammatory mediators and inflammation in the HSV-1-infected cornea. AB - We investigated whether IL-10 produced endogenously would influence the development of HSV-1-induced acute corneal disease. Murine corneal epithelial cells and fibroblasts cultured in vitro expressed IL-10 mRNA and protein constitutively and also IL-10 receptors. Inclusion of IL-10 neutralizing antibody in the culture medium significantly (p<0.05) enhanced TNF-alpha-induced IL-6 and MIP-2 production by both corneal cell types. Endogenous IL-10 synthesis, which also occurred in vivo, was not modulated by Herpes virus infection or by depletion of neutrophils or natural killer cells. Antibody to IL-10 given locally at the time of HSV-1 intracorneal infection was associated with significantly (p<0.05) enhanced production of IL-6, MIP-2, and MIP-1alpha, increased neutrophil infiltration, and more extensive corneal disease. Similarly, mice with a disrupted IL-10 gene developed more severe corneal disease than wild-type controls. Collectively, these observations suggest that locally produced IL-10 can act in an autocrine/paracrine fashion to down-regulate the production of proinflammatory mediators and thus limit corneal inflammation. PMID- 11200060 TI - Protein kinase C agonists enhance phagocytosis of P. aeruginosa by murine alveolar macrophages. AB - Pulmonary alveolar macrophages (AMphis) are incompetent to phagocytose unopsonized Pseudomonas aeruginosa, but ingestion by other macrophage phenotypes (i.e., peritoneal macrophages) occurs efficiently. The purpose of this study was to explore factors that might control such phenotypic differences. Our laboratory has demonstrated that AMphis exposed to sodium azide display enhanced phagocytosis of P. aeruginosa. Here we report that the phagocytic-enhancing effect of sodium azide was abrogated by inhibitors of protein kinase C (PKC). Furthermore, the addition of PKC agonists, such as phorbol myristate acetate (PMA), and tumor necrosis factor alpha (TNF-alpha), mimicked the phagocytic enhancing effect of sodium azide. We conclude that AM4phis are normally incompetent to phagocytose P. aeruginosa. Factors that up-regulate AMphi function (azide, PMA, TNF-alpha) can reverse the phagocytic incompetence in vitro. Although these compounds are not appropriate candidate therapeutic agents, their effects provide insights for understanding of the pathways responsible for regulation of P. aeruginosa phagocytosis. PMID- 11200061 TI - Transcriptional activation of the gp91phox NADPH oxidase subunit by TPA in HL-60 cells. AB - The exposure to epigenetic effectors capable of inducing copious production of reactive oxygen species (ROS) has been associated with chronic inflammation, tumor initiation, and promotion. The objective of this study was to examine the regulation of gp91phox, the catalytic subunit of the NADPH oxidase, and the kinetics of ROS production in promyelocytic leukemia HL-60 cells induced with 12 O-tetradeconylphorbol-13-acetate (TPA). The treatment of HL-60 cells with TPA (0.1 microM) induced cellular differentiation, which was followed after 48 h by a tenfold increase in chemiluminescence from lucigenin and a 2.5-fold increase in the intracellular oxidation of 2',7'-dicholorofluorescin (DCFH). Whereas higher concentrations (1.0 microM) of TPA did not stimulate further ROS production, repeated stimulation with 0.1 microM TPA of differentiated cells induced a modest (1.2-fold) but rapid (15 min) increase in chemiluminescence. In cells treated with TPA, the burst in ROS at 48 h was preceded by accumulation at 12 h of gp91phox (8.8-fold) and p47phox mRNA (threefold), whereas untreated cells contained steady-state levels of both transcripts. Time-course experiments with actinomycin D to inhibit transcription revealed that TPA did not improve the stability of gp91phox. In transient transfections, luciferase reporter activity directed from a 1.5-kb gp91phox promoter fragment was enhanced threefold upon treatment with TPA for 24 h. We conclude that TPA can commit HL-60 cells to differentiation and elicit transcription from the proximal gp91phox promoter. PMID- 11200062 TI - Modulation of H2 histamine receptor-mediated cAMP generation and granulocytic differentiation by extracellular nucleotides via activation of protein kinase C. AB - Extracellular ATP exerts a variety of biological actions through several kinds of P2 receptor in HL-60 promyelocytes. We show that stimulation of P2Y2 receptors with ATP and analogs resulted in the inhibition of a subsequently histamine induced cAMP production and functional differentiation. Treatment of the cells with phorbol 12-myristate 13-acetate also blocked the histamine-mediated cAMP generation just as ATP did. Incubation of the cells with the protein kinase C inhibitor bisindolylmaleimide (GF109203X) abolished the inhibitory effects of extracellular nucleotides, suggesting that protein kinase C may act as an inter regulator between two receptors. However, ATP did not affect the binding affinity or total binding of [3H]histamine to membrane receptors; it also did not heterologously desensitize H2 receptors. The ATP treatment synergistically elevated the cAMP levels induced directly by forskolin or indirectly by G protein activation after cholera toxin treatment. This indicates that the site of the protein kinase C action is not the G protein or effector enzyme. Co-stimulation of the cells with nucleotides and histamine inhibited histamine-mediated granulocytic differentiation, which was evaluated by looking at the extent of N formyl-methionyl-leucyl-phenylalanine responses. Taken together, the results demonstrate that extracellular nucleotides are negatively involved in the modulation of histamine signaling via activation of protein kinase C, probably by inhibiting coupling between receptor and G protein. PMID- 11200063 TI - The role of architectural transcription factors in cytokine gene transcription. AB - The strict control of cytokine gene transcription is required for the correct regulation of an immune response. Cytokine gene transcription is generally inducible and can also be cell-type specific. Promoter and enhancer regions that control the expression of these genes assemble complex arrays of transcription factors known as enhanceosomes. One important aspect of the organization of these multi-protein complexes is the presence of proteins known as architectural transcription factors. Architectural proteins influence structural aspects of enhanceosomes through protein:DNA as well as protein:protein interactions. The high mobility group I(Y) and the cold shock domain families of architectural proteins have been shown to play roles in cytokine gene transcription and will be discussed here. These families of proteins interact with specific structural features of DNA, modulate transcription factor binding to DNA, and interact directly with other transcription factors. The mechanisms by which they affect inducible cytokine gene transcription will be discussed. PMID- 11200064 TI - MAP kinase activation in macrophages. AB - Stimulation of macrophages by a variety of agents causes activation of mitogen activated protein kinases (MAPKs). Activation of MAPKs by lipopolysaccharide involves CD14 and Toll receptors. Subsequent steps still remain to be explored. Tumor necrosis factor-alpha (TNF-alpha)-induced activation of MAPKs has been shown to involve the death domain proteins (TRADD, FADD, MADD) and TRAFs. Other molecules involved in this pathway include the protein kinases, ASK1, germinal center kinase (GCK), hematopoietic progenitor kinase 1 (HPK1), and GCK-related kinase (GCKR). Although, these pathways have been described in various cell types, their role in macrophages remains to be established. The availability of knockout mice and constitutively active and dominant-negative mutants of MAPKs should greatly enhance our understanding of this field. The activation of MAPKs seems to be different in cell lines compared with primary cells. Among the macrophages, cells from different compartments show different expression of receptors and signal transduction molecules. These differences may account for differences in MAPK activation and other phenotypic differences in macrophages from different compartments. Therefore, it is important to use primary cells for studying MAPK signal-transduction pathways, and the data from cell lines should not be extrapolated to primary cells. PMID- 11200065 TI - Role of mast cells in zymosan-induced peritoneal inflammation in Balb/c and mast cell-deficient WBB6F1 mice. AB - Zymosan-induced peritonitis was investigated in mast cell-deficient WBB6F1 mice and in Balb/c mice pretreated with mast cell stabilizer (cromolyn) or antagonists of histamine receptors (mepyramine, triprolidine, cimetidine, or ranitidine). The inherited mast cell deficiency in W/Wv knockouts of WBB6F1 mice impaired significantly the level of histamine and plasma exudation (measured 30 min after stimulation) as well as the influx of exudatory leukocytes, accumulation of plasma and exudate chemoattractants, and the release of proinflammatory cytokines (TNF-alpha, IL-1beta, and IL-6) measured at 6 h of inflammation. All of those factors were fully restored after selective intraperitoneal reconstitution of W/Wv mice with bone marrow-derived mast cells from their control +/+ counterparts. Cromolyn pretreatment of Balb/c mice reduced exclusively the early plasma exudation and histamine influx. Blocking of histamine receptors inhibited not only the early plasma exudation but also temporarily diminished primary leukocyte influx and levels of MCP-1 and IL-1beta. In conclusion, mast cells play an important role in the initiation of zymosan-induced peritonitis and modulate its further course. PMID- 11200066 TI - Iron transport into mycobacterium avium-containing phagosomes from an Nramp1(Gly169)-transfected RAW264.7 macrophage cell line. AB - Nramp1 is an important determinant of innate resistance of macrophages to the growth of intracellular microorganisms. We previously showed that Nramp1 functions to transport iron from the cytoplasm into phagosomes of Mycobacterium avium-infected macrophages. The purpose of this investigation was to further characterize the factors that regulate Nramp1-mediated iron transport into phagosomes. Treatment of Nramp1(Gly169) macrophages with the lysomotrophic agents chloroquine or ammonium chloride reduced the import of iron significantly. We found that macrophage-activating cytokines, including TNF-alpha, IFN-gamma, IL 1alpha, and GM-CSF, when added prior to M. avium, increased the transport of iron into the phagosome. This increase in iron transport was not a result of an increased amount of Nramp1 protein in the phagosome nor to new protein synthesis. Treatment of Nramp1(Gly169)-transfected macrophages with inhibitors of protein kinase C (PKC) diminished the import of iron into the phagosomes. Iron import was inhibited by an anti-Nramp1 antibody against the putative fourth outer-loop region of Nramp1 but not by an anti-Nramp1 antibody against the carboxy terminus. The significance of these results on the orientation of Nramp1 in the phagosome membrane and on the transport of iron is discussed. PMID- 11200067 TI - Neutrophil survival is markedly reduced by incubation with influenza virus and Streptococcus pneumoniae: role of respiratory burst. AB - Bacterial superinfections are an important cause of morbidity and mortality during influenza A virus (IAV) epidemics. We demonstrate that incubation with the combination of IAV and Streptococcus pneumoniae caused marked reductions in survival of neutrophils in vitro compared with treatment with control buffer or IAV or S. pneumoniae alone. This cooperative effect was in part mediated by acceleration of neutrophil apoptosis as evidenced by increases in annexin-V binding and caspase-3 activation. However, GM-CSF did not increase survival of neutrophils exposed to IAV and S. pneumoniae. IAV enhanced neutrophil uptake of S. pneumoniae significantly. Furthermore, the combination of IAV and S. pneumoniae caused significantly more hydrogen peroxide production than IAV or S. pneumoniae alone. This increased respiratory burst activity contributed to the diminished neutrophil survival caused by IAV and S. pneumoniae. The NADPH oxidase inhibitor, diphenyleneiodonium, significantly improved survival of neutrophils treated with IAV and S. pneumoniae. These findings may help to explain the increased susceptibility of IAV-infected patients to infections with S. pneumoniae. PMID- 11200068 TI - Neutrophil secretory vesicles are the intracellular reservoir for GPI-80, a protein with adhesion-regulating potential. AB - The subcellular localization of GPI-80, a novel, adhesion-regulating protein, was investigated in human neutrophils. Surface expression of GPI-80 was determined by FACS analysis as well as by the ability for phospholipase C to cleave the protein from the cell surface. Increasing amounts of GPI-80 were exposed on the cell surface after weak stimulation with the chemoattractant fMLF, suggesting that the protein can be translocated to the plasma membrane from intracellular stores. By subcellular fractionation of the neutrophils, GPI-80 was defined as a component of a light membrane fraction, containing secretory vesicles and plasma membranes, and it was absent from the neutrophil granule fractions. Separation of the plasma membranes from the secretory vesicles by flotation gradient fractionation confirmed that the GPI-80 was localized in the mobilizable secretory vesicles by approximately 50%, and the rest was plasma membrane-bound. Thus, we identify secretory vesicles as the reservoir of GPI-80 from which it may translocate to the plasma membrane after weak stimulation of the cells. PMID- 11200069 TI - PAF-mediated Ca2+ influx in human neutrophils occurs via store-operated mechanisms. AB - Many inflammatory mediators activate neutrophils (PMN) partly by increasing cytosolic calcium concentration ([Ca2+]i). Modulation of PMN [Ca2+]i might therefore be useful in regulating inflammation after shock or sepsis. The hemodynamic effects of traditional Ca2+ channel blockade, however, could endanger unstable patients. Store-operated calcium influx (SOCI) is known now to contribute to Ca2+ flux in "nonexcitable" cells. Therefore, we studied the role of SOCI in human PMN responses to the proinflammatory ligand PAF. PMN [Ca2+]i was studied by spectrofluorometry with and without external calcium. We studied the effects o PMID- 11200070 TI - Adjuvant effect of gamma-inulin is mediated by C3 fragments deposited on antigen presenting cells. AB - The adjuvant effect of gamma-inulin, a strong activator of the alternative complement pathway, is well-known, but its exact mechanism is not revealed yet. Here, we show that macrophages, isolated from the peritoneal cavity of gamma inulin-injected mice and used as antigen-presenting cells, enhance the proliferation of antigen-specific T-cells up to 2.5-fold when compared with macrophages of non-treated animals. This effect is abrogated by the presence of anti-C3 F(ab')2 fragments and by prior decomplementation of the donor animals with CVF. It is demonstrated that treatment of mice with the adjuvant results in deposition of C3-fragments onto the surface of peritoneal macrophages, as does in vitro incubation of the cells with gamma-inulin in the presence of fresh autologous serum. Prior incubation of macrophages with gamma-inulin plus serum in vitro enhances subsequent C3 production. Because it has been shown earlier that CR1/2 expressed on activated T-cells and interacting with covalently bound C3 fragments plays an important role in the augmentation of the adaptive response, our present results reveal a mechanism that contributes to the adjuvant effect of gamma-inulin and point to a further link between innate and adaptive immunity. PMID- 11200071 TI - Severe exercise enhances phagocytosis by murine bronchoalveolar macrophages. AB - Because physical activity affects the immune competency of individuals by an unknown mechanism, we investigated the effect of acute exercise on phagocytosis of bronchoalveolar macrophages (BAMs). Male BALB/c mice, 7-9 weeks old, ran on a treadmill to exhaustion (severe exercise, SE) or at a final speed of 17 m/min for 30 min (moderate exercise, ME). Although both exercise protocols induced differential leukocytosis, 95% leukocytes from lung lavages of both groups were BAMs. The BAM phagocytic capacity of nonopsonized beads increased immediately after SE but not after ME, gradually returning to the basal level after 4 h. SE upregulates the macrophage scavenger receptors (SR-A type I/II and MARCO), CR3, and ICAM-1, but not Fc gammaR. Although the blocking effect of MARCO antibody was most pronounced, that of ICAM-1 antibody was totally reversed by cross-linking CR3. Our results showed that SE, but not ME, activated BAMs and that the enhanced nonopsonized phagocytosis was mainly mediated by scavenger receptors and ICAM 1/CR3. PMID- 11200072 TI - CpG DNA increases primary malignant B cell expression of costimulatory molecules and target antigens. AB - Multiple factors, including expression of costimulatory molecules, antigen presenting molecules, and target antigens, likely impact the efficacy of antibody therapy and other approaches to the immunotherapy of B cell malignancy. Unmethylated CpG-dinucleotides in select base contexts ("CpG motifs") that resemble sequences found in bacterial DNA are potent immunostimulatory agents capable of inducing a complex immune response, including a strong B cell stimulus. We examined the effect of a potent human CpG oligonucleotide (CpG ODN 2006) on different types of primary human malignant B cells and reactive follicular hyperplasia. CpG oligodeoxynucleotide (CpG ODN), but not control (non CpG ODN), increased the expression of costimulatory molecules (CD40, CD80, CD86, CD54) on malignant B cells without altering the phenotype of B cells obtained from reactive follicular hyperplasia. CpG ODN also enhanced expression of class I and class II MHC in most samples. CD20 expression was increased in response to CpG ODN, most notably in B-CLL and marginal zone lymphoma. An inverse correlation was found between baseline expression of CD20 and CD40 and their expression after exposure to CpG ODN, thus the most significant increase in expression of these molecules was found in those samples that had the lowest baseline levels. In conclusion, CpG ODN can lead to increasing expression of molecules involved in costimulation, antigen presentation, and as targets for antibody-based therapy and deserve further evaluation as potential immunotherapeutic agents for B cell malignancy. PMID- 11200074 TI - Natural and synthetic agonists of the melanocortin receptor type 3 possess anti inflammatory properties. AB - The effects of the natural and synthetic ligands for the melanocortin receptor type 3 (MC3-R) have been evaluated in a murine model of experimental gout. Systemic treatment of mice with gamma2-melanocyte-stimulating hormone (gamma2 MSH) and the synthetic agonist MTII inhibited accumulation of KC, interleukin-1 beta (IL-1beta), and PMN elicited by urate crystals in the peritoneal cavity. In vitro, macrophage (Mo) activation, determined as release of KC and IL-1beta, was inhibited by gamma2-MSH and MTII. The mixed MC3/4-R antagonist SHU9119 prevented the inhibitory actions of gamma2-MSH and MTII in vitro and in vivo, whereas the selective MC4-R antagonist HS024 was without effect. Western blotting also showed the presence of MC3-R protein on murine peritoneal Mo. Furthermore, agonism at the MC3-R evoked accumulation of cAMP within the Mo, which was inhibited by SHU9119. Thus, naturally occurring melanocortins, as well as the synthetic long acting compound MTII, activate MC3-R on peritoneal Mo to inhibit the experimental inflammatory response. PMID- 11200073 TI - Subthreshold concentrations of anti-proteinase 3 antibodies (c-ANCA) specifically prime human neutrophils for fMLP-induced leukotriene synthesis and chemotaxis. AB - Anti-neutrophil cytoplasmic antibodies (ANCA) targeting proteinase 3 (PR3) possess a high sensitivity and specificity for Wegener's granulomatosis. Due to their capacity of directly activating neutrophils, a pathogenetic role for these autoantibodies has been proposed. We investigated the impact of subthreshold concentrations of monoclonal anti-PR3 antibodies (anti-PR3; 0.1 microg/mL) on neutrophil activation elicited by a secondary agent. Preincubation with anti-PR3 resulted in a massive amplification of N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced leukotriene (LT) generation, with a marked increase in the liberation of LTB4, LTA4, and 5-hydroxyeicosatetraenoic acid (5-HETE). This priming commenced within 2.5 min, with a maximum after 5-7.5 min. Moreover, anti PR3 pretreatment markedly enhanced PMN movement toward fMLP. The priming effect of anti-PR3 toward fMLP challenge was reproduced by c-ANCA, but not by F(ab)2 fragments of the antibodies and isotype-matched control IgG. Generation of superoxide anion and release of elastase were suppressed in anti-PR3-pretreated neutrophils undergoing fMLP challenge. In contrast, neutrophil activation by platelet-activating factor (PAF) or the calcium ionophore A23187 remained unaffected. We conclude that subthreshold concentrations of anti-PR3 antibodies selectively modify neutrophil responses to fMLP, with enhancement of leukotriene generation and chemotaxis, but suppression of respiratory burst and degranulation. Such priming might contribute to localized neutrophil accumulation together with blunted host defense in Wegener's granulomatosis. PMID- 11200075 TI - Modelling in surgical oncology--part III: massive data sets and complex systems. AB - Human tumours are complex and unstable biological systems. New intellectual and mathematical approaches together with massive computing power are transforming our capacity to model and investigate such complexity. Computers also allow massive data sets to be collated and analysed. Such sets include the medical and epidemiological records of entire populations; the entire genetic code of the human being and of other species, including parasites and disease vectors; and the genotype of each and every individual. Massive data sets take us into new dimensions of complexity for which simple linear mathematics are insufficient. The analysis of the grades of complexity which determine protein and cell construction, cell to cell interactions within tissues and organs, the morphogenesis of entire organisms and population interactions with disease vectors require the sophisticated mathematical tools of non-linear analysis, neural networks, chaos and complexity theory. The capacity for closer representations of reality through powerful computational models also allows us to look afresh at the generalizations of conventional statistics. Within this computational cauldron, we may also find help in the better understanding of oncogenesis and cancer therapy. This paper, the third in our series on modelling in tumour biology, considers the breadth of opportunity and challenge at the interface between cell biology and biomathematics. PMID- 11200076 TI - Immunohistochemical analysis of measles related antigen in IBD. PMID- 11200077 TI - Survivin gene expression and prognosis in recurrent colorectal cancer. PMID- 11200078 TI - The role of nitric oxide in the regulation of ion channels in airway epithelium: implications for diseases of the lung. AB - The human respiratory tract is covered with airway surface liquid (ASL) that is essential for lung defense and normal airway function. The quantity and composition of ASL is regulated by active ion transport across the airway epithelium. Abnormal electrolyte transport produces changes in ASL volume and composition, inhibits mucociliary clearance and leads to chronic infection of airway surfaces, as is evident in cystic fibrosis. Agonists that induce intracellular increases in cAMP or Ca2+ are generally associated with electrolyte secretion. While these mechanisms have been studied in detail for many years, modulation of ion channels by nitric oxide (NO) has emerged only recently as a significant determinant of ion channel function. NO is a physiological regulator of transepithelial ion movement and alterations of its generation and action may play an important role in the pathogenesis of lung disorders characterized by hypersecretion of ASL. This review presents the current understanding of regulation of airway epithelial ion channels by NO and attempts to highlight the importance of this regulation for lung defense. PMID- 11200079 TI - Mechanisms of biological S-nitrosation and its measurement. AB - Nitric oxide (NO) exhibits multiple biological actions through formation of various oxidized intermediates derived from NO. Among them, nitrosothiol adducts (RS-NOs) with the sulfhydryl moiety of proteins and amino acids appears to be an important species in view of its unique chemical reactivity. Understanding of the biologically relevant S-nitrosation mechanism is essential because RS-NOs seem to be critically involved in modulation of intracellular and intercellular signal transduction, including gene transcription, cell apoptosis, and oxidative stress. RS-NOs have been recently found to be formed efficiently via one-electron oxidation of NO catalyzed by ceruloplasmin, a major copper-containing protein in mammalian plasma. Ceruloplasmin is synthesized mainly by hepatocytes, but it is also expressed by other cells such as macrophages and astrocytes. Once RS-NOs are formed, they function as NO transporters in biological systems, the NO being transferred to different sulfhydryls of various biomolecules. This transfer may be mediated by transnitrosation reactions occurring chemically or enzymatically by a means of specific enzymes such as protein disulfide isomerase. The molecular mechanism of biological S-nitrosation is discussed as related to the important physiological and pathophysiological functions of RS-NOs. Also, RS-NO assays that are being successfully used for detection of biological S-nitrosation are briefly reviewed. PMID- 11200080 TI - Plasma protein carbonyls in nonpregnant, healthy pregnant and preeclamptic women. AB - Increased reactive oxygen species (ROS) and lipid peroxidation may be implicated in the pathogenesis of preeclampsia by causing cell (membrane) damage and impaired endothelial function. Carbonyl derivatives of proteins, or protein carbonyls, may be sensitive biomarkers of ROS-mediated damage. The aim of the study was to compare levels of protein carbonyls in plasma of preeclamptic, healthy pregnant and healthy nonpregnant women. Plasma protein carbonyls were measured in 47 preeclamptic, 45 healthy pregnant and 22 healthy nonpregnant women by using a sensitive ELISA-method. ANOVA, the unpaired t-test and Pearson's correlation were used for statistical analysis. Preeclamptic women had significantly higher plasma protein carbonyl levels than healthy pregnant women (P < 0.0001). Healthy pregnant women showed significantly higher protein carbonyl levels (P < 0.001) as compared to nonpregnant controls. The higher levels of protein carbonyls as compared to nonpregnant controls suggest that increased oxygen free radical damage occurs in normal pregnancy and to a much higher extent in preeclampsia. PMID- 11200081 TI - Calcium-dependent mitochondrial formation of species promoting strand scission of genomic DNA in U937 cells exposed to tert-butylhydroperoxide: the role of arachidonic acid. AB - Treatment of U937 cells with a sublethal concentration of tert-butylhydroperoxide generates DNA single strand breakage in U937 cells and this response is increased by caffeine, ATP, pyruvate or antimycin A. As we previously reported (Guidarelli, Clementi, Brambilla and Cantoni, (1997) Biochem. J. 328, 801-806), the enhancing effects of antimycin A are mediated by inhibition of complex III and the ensuing formation of superoxides and hydrogen peroxide in a reaction in which ubisemiquinone serves as an electron donor. Active electron transport was required in pyruvate-supplemented cells since the increased genotoxic response occurred as a consequence of enforced mitochondrial Ca2+ accumulation, a process driven by the increased electrochemical gradient. The enhancing effects of caffeine or ATP were also the consequence of mitochondrial Ca2+ accumulation but these responses were independent on electron transport. The increased formation of DNA lesions resulting from exposure to tert-butylhydroperoxide associated with the Ca2+-mobilizing agents or the respiratory substrate was mediated by arachidonic acid generated by Ca2+-dependent activation of phospholipase A2. Melittin, a potent phospholipase A2 activator, and reagent arachidonic acid mimicked the effects of caffeine, ATP or pyruvate on the tert-butylhydroperoxide induced DNA single strand breakage. PMID- 11200082 TI - Photosensitized formation of singlet oxygen by phycobiliproteins in neutral aqueous solutions. AB - Phycobiliproteins (PBPs) are a type of promising sensitizers for photodynamic therapy (PDT). Upon irradiation (lambda>500nm) of an oxygen-saturated aqueous solution of phycobiliproteins, particularly, C-phycocyanin (C-PC), allophycocyanin (APC) or R-phycoerythrin (R-PE), the formation of singlet oxygen (1O2) was detected by using imidazole in the presence of p-nitrosodimethylaniline (RNO). The bleaching of RNO caused by the presence of imidazole in our system showed typical concentration dependence with a maximum at about 8mM imidazole, which is in agreement with the formation of 1O2. In addition, the generation of 1O2 was verified further in the presence of D2O and specific singlet oxygen quencher 1,4-diazabicyclo [2,2,2] octane (DABCO) and sodium azide (NaN3). Our experimental results indicated that APC possesses high ability to generate reactive oxygen species and the relative quantum yields of photogeneration of 1O2 by PBPs are as follows: APC > C-PC > R-PE. PMID- 11200083 TI - Vinpocetine attenuates the metabolic dysfunction induced by amyloid beta-peptides in PC12 cells. AB - The cytoprotective effect of vinpocetine [14-ethoxycarbonyl-(3alpha, 16alpha ethyl)-14,15-eburnamine] was investigated on PC12 cells treated with the amyloid beta-peptides (Abeta) for 24 hours. Vinpocetine was shown to protect cells from the inhibition in redox status induced by exposure to Abeta25-35 and Abeta1-40, the maximal protection being achieved at a vinpocetine concentration of 40 microM. At this concentration, vinpocetine blocked the inhibition of the mitochondrial respiratory chain complexes II-III and IV and completely abolished the depletion of pyruvate levels induced by toxic concentrations of Abeta peptides. Furthermore, the accumulation of ROS in cells exposed to Abeta25-35 and Abeta1-40 evaluated using the fluorescent probe 2',7'-dichlorofluorescin (DCF), was reduced in the presence of 40 microM vinpocetine. Taken together, the data presented herein demonstrate that vinpocetine protects cells from Abeta toxicity, preventing the generation of oxidative stress due to the excessive accumulation of ROS. This study suggests that vinpocetine can exert neuroprotective properties which might be of importance and contribute to its clinical efficacy in the treatment of Alzheimer's disease or other neurodegenerative disorders in which oxidative stress is involved. PMID- 11200084 TI - Oxidative stress increases potassium efflux from pancreatic islets by depletion of intracellular calcium stores. AB - Oxidative stress to B-cells is thought to be of relevance in declining B-cell function and in the process of B-cell destruction. In other tissues including heart, brain and liver, oxidative stress has been shown to elevate the intracellular free calcium concentration and to provoke potassium efflux. We studied the effect of oxidative stress on Ca2+ and K+ (Rb+) outflow from pancreatic islets using the thiol oxidants DIP and BuOOH. Both compounds reversibly increased 86Rb+ efflux in the presence of 3 and 16.7 mmol/l glucose. Stimulation of 86Rb+ efflux was also evident in the absence of calcium. DIP evoked release of 45Ca2+ from the pancreatic islets both in the presence or absence of extracellular calcium. Employing inhibitors of the calcium-activated potassium channel (KCa) and the high conductance K+-channel (BKCa), the effect of DIP on 86Rb+ efflux was slightly diminished. Tolbutamide had no effect on 86Rb+ efflux in the presence of DIP. On the other hand thapsigargin, a blocker of the Ca+-ATPase of the endoplasmic reticulum, completely suppressed the DIP-mediated 86Rb+ outflow. The data suggest that thiol oxidant-induced potassium efflux from pancreatic islets is mainly mediated through liberation of intracellular calcium and subsequent stimulation of calcium-activated potassium efflux. PMID- 11200085 TI - Glutathione loading prevents free radical injury in red blood cells after storage. AB - We have previously demonstrated that the loss of glutathione (GSH) and GSH peroxidase (GSH-PX) in banked red blood cells (RBCs) is accompanied by oxidative modifications of lipids, proteins and loss of membrane integrity. The objective of this study was to determine whether artificial increases in antioxidant (GSH) or antioxidant enzyme (catalase) content could protect membrane damage in the banked RBCs following an oxidant challenge. RBCs stored at 1-6 degrees C for 0, 42 and 84 days in a conventional additive solution (Adsol) were subjected to oxidative stress using ferric/ascorbic acid (Fe/ASC) before and after enriching them with GSH or catalase using a hypotonic lysis-isoosmotic resealing procedure. This lysis-resealing procedure in the presence of GSH/catalase raised intracellular GSH and catalase concentrations 4-6 fold, yet produced only a small reduction in mean cell volume (MCV), mean cell hemoglobin (MCH) and mean cell hemoglobin concentrations (MCHC). Indicators of oxidative stress and membrane integrity were measured, including acetylcholinesterase (AChE) activity, GSH concentration, phosphatidylserine (PS) externalization (prothrombin-converting activity) and transmembrane lipid movements (14C-lyso phosphatidylcholine flip flop and PS transport). GSH-enrichment protected AChE activity in fresh (0 day) and stored (42 and 84 days) RBCs from Fe/ASC oxidation by 10, 23 and 26%, respectively, compared with not-enriched controls. Following oxidative stress, the rate of transbilayer lipid flip-flop did not increase in fresh cells, but increased 9.3% in 42-day stored cells. Phosphatidylserine exposure, as measured by prothrombinase activity, increased 2.4-fold in fresh and 5.2-fold in 42-day stored cells exposed to Fe/ASC. Previous studies have shown that 42-day storage causes a moderate decrease in PS transport (approximately 50%), whereas transport rates declined by up to 75% in stored RBCs when challenged with Fe/ASC. GSH enrichment prevented the increase in passive lipid flip-flop and the increase in prothrombinase activity, but offered no protection against oxidative damage of PS transport. In contrast to these effects, catalase-enrichment failed to protect GSH levels and AChE activity upon oxidative stress. Membrane protein thiol oxidation was assessed by labeling reactive protein thiols with 5 acetalamidofluorescein followed by immunoblotting with antifluorescein antibodies. Significant oxidation of membrane proteins was confirmed by a greater loss of thiols in stored RBCs than in fresh RBCs. These results demonstrate that it may be possible to prevent storage-mediated loss of AChE, increased lipid flip flop, and increased PS exposure, by maintaining or increasing GSH levels of banked RBCs. PMID- 11200086 TI - Involvement of abscisic acid-dependent and -independent pathways in the upregulation of antioxidant enzyme activity during NaCl stress in cotton callus tissue. AB - The role of abscisic acid (ABA) in the signal transduction pathway associated with NaCl-induced up-regulation of antioxidant enzyme activity was examined in a NaCl-tolerant cotton callus cell line treated with NaCl, ABA, paraquat, or H2O2 in the presence and absence or fluridone, an inhibitor of terpene, and therefore, ABA synthesis. Treatment with NaCl resulted in a rapid increase (within 30 minutes) in the ABA levels of the callus tissue, and the NaCl, ABA, and paraquat treatments induced rapid increases in the activities of superoxide dismutase, catalase, peroxidase, and glutathione reductase. Pre-treatment with fluridone significantly suppressed the NaCl-induced increases, but only slightly delayed the increases in tissue subjected to exogenous ABA treatment. This implies that ABA is involved in the signal transduction pathway associated with the NaCl induced up-regulation of these antioxidant enzymes. Pre-treatment with fluridone had no effect on the paraquat-induced increases, suggesting that these enzymes can also be up-regulated by a pathway other than the one mediated by ABA. Both the NaCl and paraquat treatments produced significant increases in the superoxide levels within the callus, but the increase resulting from the paraquat treatment was significantly higher than the increase resulting from the NaCl treatment. These data suggest that NaCl stress results in the production of reactive oxygen intermediates (ROI) which signals the induction of an ABA-dependent signaling pathway. The production of very high levels of ROI, such as those that occur with paraquat treatment or perhaps during periods of prolonged or extreme stress, may induce an ABA-independent signaling pathway. PMID- 11200087 TI - Superoxide, amine buffers and tetranitromethane: a novel free radical chain reaction. AB - The amine buffer Tris slowly reduces tetranitromethane (TNM) to the nitroform anion in a non-accelerating reaction. The amine buffers HEPES and MOPS also (slowly) react with TNM but the dialkylaminoalkyl radicals formed from these two buffers undergo further reactions resulting in a rapid, accelerating, free radical chain process whereby the amine is oxidized and TNM reduced. The chemical functionality in any reaction component, not necessarily the buffer, required for this radical chain mechanism is >N-CH<. In the presence of such groups, the quantification of superoxide by TNM is impossible. PMID- 11200088 TI - DNA-breaking versus DNA-protecting activity of four phenolic compounds in vitro. AB - Given the paradoxical effects of phenolics in oxidative stress, we evaluated the relative pro-oxidant and antioxidant properties of four natural phenolic compounds in DNA nicking. The phenolic compounds differed dramatically in their ability to nick purified supercoiled DNA, with the relative DNA nicking activity in the order: 1,2,4-benzenetriol (100% nicking) > gallic acid > caffeic acid > gossypol (20% nicking). Desferrioxamine (0.02 mM) decreased DNA strand breakage by each phenolic, most markedly with gallate (85% protection) and least with caffeic acid (26% protection). Addition of metals accelerated DNA nicking, with copper more effective (approximately 5-fold increase in damage) than iron with all four phenolics. Scavengers revealed the participation of specific oxygen derived active species in DNA breakage. Hydrogen peroxide participated in all cases (23-90%). Hydroxyl radicals were involved (32-85%), except with 1,2,4 benzenetriol. Superoxide participated (81-86%) with gallic acid and gossypol, but not with caffeic acid or 1,2,4-benzenetriol. With 1,2,4-benzenetriol, scavengers failed to protect significantly except in combination. Thus, in the presence of desferrioxamine, catalase or superoxide dismutase inhibited almost completely. When DNA breakage was induced by Fenton's reagent (ascorbate plus iron) the two catechols (caffeic acid and gossypol) were protective, whereas the two triols (1,2,4-benzenetriol and gallic acid) exacerbated damage. PMID- 11200089 TI - Arguments against the significance of the Fenton reaction contributing to signal pathways under in vivo conditions. AB - One of the common explanations for oxidative stress in the physiological milieu is based on the Fenton reaction, i.e. the assumption that radical chain reactions are initiated by metal-catalyzed electron transfer to hydrogen peroxide yielding hydroxyl radicals. On the other hand - especially in the context of so-called "iron switches" - it is postulated that cellular signaling pathways originate from the interaction of reduced iron with hydrogen peroxide. Using fluorescence detection and EPR for identification of radical intermediates, we determined the rate of iron complexation by physiological buffer together with the reaction rate of concomitant hydroxylations of aromatic compounds under aerobic and anaerobic conditions. With the obtained overall reaction rate of 1,700 M(-1)s(-1) for the buffer-dependent reactions and the known rates for Fenton reactions, we derive estimates for the relative reaction probabilities of both processes. As a consequence we suggest that under in vivo conditions initiation of chain reactions by hydroxyl radicals generated by the Fenton reaction is of minor importance and hence metal-dependent oxidative stress must be rather independent of the so-called "peroxide tone". Furthermore, it is proposed that - in the low (subtoxic) concentration range - hydroxylated compounds derived from reactions of "non-free" (crypto) OH radicals are better candidates for iron-dependent sensing of redox-states and for explaining the origin of cellular signals than the generation of "free" hydroxyl radicals. PMID- 11200090 TI - Comparison of LDL trap assay to other tests of antioxidant capacity; effect of vitamin E and lovastatin treatment. AB - Oxidized low density lipoprotein (LDL) has a major impact in the development of atherosclerosis. Risk for oxidative modification of LDL is usually determined indirectly by measuring the capability of LDL to resist radical insult. We compared three different methods quantifying the antioxidative capacity of LDL ex vivo in dyslipidemic patients with coronary heart disease. Plasma samples were obtained from two double-blinded cross-over trials. The duration of all interventions (placebo, lovastatin 60 mg/day, RRR-alpha-tocopherol 300 mg/day and lovastatin + RRR-alpha-tocopherol combined) was 6 weeks. The total radical capturing capacity of LDL (TRAP) in plasma was determined using 2,2-azo-bis(2,4 dimethyl-valeronitrile) (AMVN) -induced oxidation, and measuring the extinction time of chemiluminescence. TRAP was compared to the variables characterizing formation of conjugated dienes in copper-induced oxidation. Also the initial concentrations and consumption times of reduced alpha-tocopherol (alpha-TOH) and ubiquinol in AMVN-induced oxidation were determined. Repeatability of TRAP was comparable to that of the lag time in conjugated diene formation. Coefficient of variation within TRAP assay was 4.4% and between TRAP assays 5.9%. Tocopherol supplementation produced statistically significant changes in all antioxidant variables except those related to LDL ubiquinol. TRAP increased by 57%, the lag time in conjugated diene formation by 34% and consumption time of alpha-TOH by 88%. When data of all interventions were included in the analyses, TRAP correlated with the lag time (r = 0.75, p < 10(-6)), with LDL alpha-TOH (r = 0.50, p < 0.001) and with the consumption time of alpha-TOH (r = 0.58, p < 0.0001). In the baseline data, the associations between different antioxidant variables were weaker. TRAP correlated with the lag time (r = 0.55, p < 0.001) and alpha-TOH consumption time (r = 0.48, p < 0.05), and inversely with apolipoprotein Al (r = -0.51, p < 0.05). Lag time at the baseline did not correlate with ubiquinol or tocopherol parameters, or with any plasma lipid or lipoprotein levels analyzed. Lovastatin treatment did not significantly affect the antioxidant capacity of LDL. In conclusion, TRAP reflects slightly different properties of LDL compared to the lag time. Thus, LDL TRAP assay may complement the other methods used to quantify the antioxidant capacity of LDL. However, TRAP and the lag time react similarly to vitamin E supplementation. PMID- 11200091 TI - Effect of ozone treatment on reactive oxygen species and adenosine production during hepatic ischemia-reperfusion. AB - This study investigates whether ozone could confer protection from hepatic ischemia reperfusion by modifying the accumulation of adenosine and xanthine during ischemia. A significant increase in both adenosine and xanthine accumulation was observed as a consequence of ATP degradation during hepatic ischemia. Adenosine exerts a protective effect on hepatic ischemia reperfusion injury since the elimination of endogenous adenosine accumulation with adenosine deaminase increased the hepatic injury associated with this process. On the other hand, the high xanthine levels observed after ischemia could exert deleterious effects during reperfusion due to reactive oxygen species generation from xanthine oxidase. The administration of allopurinol, an inhibitor of xanthine oxidase, attenuated the increase in reactive oxygen species and transaminase levels observed after hepatic reperfusion. Ozone treatment in liver maintained adenosine levels similar to those found after ischemia but led to a marked reduction in xanthine accumulation. In order to evaluate the role of both adenosine and xanthine, we tried to modify the protection confered by ozone, by modifying the concentrations of adenosine and xanthine. The metabolization of endogenous adenosine after ischemia abolished the protective effect conferred by ozone. When xanthine was administered previous to ozone treatment, the protection conferred by adenosine disappeared, showing both postischemic reactive oxygen species and transaminase levels similar to those found after hepatic ischemia reperfusion. Ozone would confer protection against the hepatic ischemia reperfusion injury by the accumulation of adenosine that in turns benefits the liver and by blocking the xanthine/xanthine oxidase pathway for reactive oxygen species generation. PMID- 11200092 TI - In vitro study of the antioxidant properties of non steroidal anti-inflammatory drugs by chemiluminescence and electron spin resonance (ESR). AB - OBJECTIVES: To determine the antioxidant activities of nonsteroidal anti inflammatory drugs (NSAIDS), we examined by chemiluminescence (CL) and electron spin resonance (ESR) their scavenging properties towards lipid peroxides, hypochlorous acid and peroxynitrite. METHODS: The antioxidant properties of nimesulide (NIM), 4-hydroxynimesulide (4-HONIM), aceclofenac (ACLO), 4 hydroxyaceclofenac (4-HOA-CLO), diclofenac (DICLO) and indomethacin (INDO) were tested on four different reactive oxygen species (ROS) generating systems: (I) phorbol-myristate acetate (PMA)-activated neutrophils, (II) Fe2+/ascorbate induced lipid peroxidation, (III) HOCl-induced light emission, (IV) the kinetics of ONOO- decomposition followed by spectrophotometry. ROS production was monitored by luminol-enhanced CL or by ESR using two different spin traps. RESULTS: At 10 microM, ACLO, NIM, 4-HONIM, 4-HOA-CLO, and DICLO decreased luminol enhanced CL generated by PMA-activated neutrophils. Inversely, INDO increased the luminol enhanced CL. Interestingly, hydroxylated metabolites were more potent antioxidants than the parent drugs. Furthermore, all drugs tested, excepted ACLO, lowered lipid peroxidation induced by Fe2+/ascorbate system. ACLO and DICLO, even at the highest concentration tested (100 microM), did not significantly lower HOCl induced CL, whereas the other drugs were potent scavengers. Finally, all the NSAIDS accelerated decomposition of ONOO-, suggesting a potential capacity of the molecules to scavenge peroxynitrite. CONCLUSION: The NSAIDs possess variable degrees of antioxidant activities, linked to their ability to react with HOCl, lipid peroxides or ONOO-. These antioxidant activities could offer interesting targeted side-effects in the treatment of joint inflammatory diseases. PMID- 11200093 TI - Distinct mechanisms of DNA damage in apoptosis induced by quercetin and luteolin. AB - Quercetin has been reported to have carcinogenic effects. However, both quercetin and luteolin have anti-cancer activity. To clarify the mechanism underlying the carcinogenic effects of quercetin, we compared DNA damage occurring during apoptosis induced by quercetin with that occuring during apoptosis induced by luteolin. Both quercetin and luteolin similarly induced DNA cleavage with subsequent DNA ladder formation, characteristics of apoptosis, in HL-60 cells. In HP 100 cells, an H2O2-resistant clone of HL-60 cells, the extent of DNA cleavage and DNA ladder formation induced by quercetin was less than that in HL-60 cells, whereas differences between the two cell types were minimal after treatment with luteolin. In addition, quercetin increased the formation of 8-oxo-7,8-dihydro-2' deoxyguanosine (8-oxodG), an indicator of oxidative DNA damage, in HL-60 cells but not in HP 100 cells. Luteolin did not increase 8-oxodG formation, but inhibited topoisomerase II (topo II) activity of nuclear extract more strongly than quercetin and cleaved DNA by forming a luteolin-topo II-DNA ternary complex. These results suggest that quercetin induces H2O2-mediated DNA damage, resulting in apoptosis or mutations, whereas luteolin induces apoptosis via topo II mediated DNA cleavage. The H2O2-mediated DNA damage may be related to the carcinogenic effects of quercetin. PMID- 11200094 TI - Bioavailability of (-)-epicatechin upon intake of chocolate and cocoa in human volunteers. AB - We evaluated the levels of (-)-epicatechin (EC) and its metabolites in plasma and urine after intake of chocolate or cocoa by male volunteers. EC metabolites were analyzed by HPLC and LC/MS after glucuronidase and/or sulfatase treatment. The maximum levels of total EC metabolites in plasma were reached 2 hours after either chocolate or cocoa intake. Sulfate, glucuronide, and sulfoglucuronide (mixture of sulfate and glucuronide) conjugates of nonmethylated EC were the main metabolites present in plasma rather than methylated forms. Urinary excretion of total EC metabolites within 24 hours after chocolate or cocoa intake was 29.8+/ 5.3%'; and 25.3+/-8.1% of total EC intake. EC in chocolate and cocoa was partly absorbed and was found to be present as a component of various conjugates in plasma, and these were rapidly excreted in urine. PMID- 11200095 TI - Inhibition of lipoprotein oxidation by prenylated xanthones derived from mangostin. AB - Oxidative damage is thought to play a critical role in cardiovascular and other chronic diseases. This has led to considerable interest in the antioxidant activity of dietary compounds. Flavonoids have received the most attention and much is known about the structural requirements for antioxidant activity. However, little is known about the antioxidant activity of other plant derived phenolic compounds such as the xanthones. We have previously shown that the prenylated xanthone, mangostin, can inhibit the oxidation of low density lipoprotein. In order to examine the effects of structure modification on antioxidant activity of this class of compound we have prepared a number of derivatives of mangostin and tested antioxidant activity in an isolated LDL and plasma assay. The results of this study show that structural modification of mangostin can have a profound effect on antioxidant activity. Derivatisation of the C-3 and C-6 hydroxyl groups with either methyl, acetate, propane diol or nitrile substantially reduces antioxidant activity. In contrast, derivatisation of C-3 and C-6 with aminoethyl derivatives enhanced antioxidant activity, which may be related to changes in solubility. Cyclisation of the prenyl chains had little influence on antioxidant activity. PMID- 11200097 TI - Quercetin 3-O-beta-glucoside is better absorbed than other quercetin forms and is not present in rat plasma. AB - The effect of the nature of the sugar moiety on quercetin absorption has been investigated in rats. Four groups of rats received an experimental meal containing 20 mg of quercetin equivalents, supplied as quercetin, quercetin 3-O beta-glucoside, quercetin 3-O-beta-rhamnoside or rutin. Four hours after the meal, the metabolites identified in hydrolysed plasma were identical in all groups (3'- and 4'-methylquercetin). However, the total concentration of metabolites was markedly different: 11.2+/-1.8, 2.5+/-2.0 and 33.2+/-3.5 microM for the quercetin, rutin, and quercetin 3-glucoside meals respectively. After quercetin 3-rhamnoside consumption, we failed to detect any metabolites in the plasma. These data suggest that the 3-O-glucosylation improves the absorption of quercetin in the small intestine, whereas the binding of a rhamnose to the aglycone markedly depresses it. Additional experiments have shown that the higher plasma levels measured after quercetin 3-glucoside meal compared to the quercetin meal were maintained throughout the 24-hour period following the meal. Using a multi-electrode coulometric detection, together with suitable chromatographic conditions, we were able to distinguish between the conjugated and the glycosylated forms. Thus, we clearly showed the absence of quercetin 3-O-beta glucoside in the plasma from rats fed a diet containing this glucoside. This result suggests that quercetin 3-O-beta-glucoside is hydrolysed before or during its intestinal absorption. PMID- 11200096 TI - Activity of artichoke leaf extract on reactive oxygen species in human leukocytes. AB - Artichoke leaf extract was studied in human leukocytes for activity against oxidative stress using flow cytometry and dichlorofluorescin diacetate as a fluorescence probe. It produces a concentration-dependent inhibition of oxidative stress when cells are stimulated with agents that generate reactive oxygen species (ROS): hydrogen peroxide, phorbol-12-myristate-13-acetate (PMA), and N formyl-methionyl-leucyl-phenylalanine (FMLP). Cynarin, caffeic acid, chlorogenic acid, and luteolin, constituents of artichoke leaf extract, also show a concentration-dependent inhibitory activity in the above models, contributing to the antioxidant activity of the extract in human neutrophils. PMID- 11200099 TI - Exploring the connection between pornography and sexual violence. AB - This article examines the relationship between sexual violence and pornography. Data about women's experiences of sexual violence and their abusers' use of pornography were collected at a rape crisis center from 100 survivors. Findings include that 28% of respondents reported that their abuser used pornography and that for 12% of the women, pornography was imitated during the abusive incident. The effects of pornography on women's experiences of sexual violence are discussed. PMID- 11200098 TI - Retinol supplementation induces DNA damage and modulates iron turnover in rat Sertoli cells. AB - Recent intervention studies revealed that supplementation with retinoids resulted in a higher incidence of lung cancer. Recently the causal mechanism has begun to be clarified. We report here that retinol caused cellular DNA damage probably involving cellular iron accumulation. Retinol (7 microM) significantly induced DNA single strands breaks, DNA fragmentation and production of 8-oxo-7, 8-dihydro 2'-deoxyguanosine in cultured Sertoli cells. In contrast, lower doses seemed not to induce single-strands break in this experimental model. The breaks in DNA were inhibited by an iron scavenger; and 7 microM retinol treatment modulated iron turnover leading to iron accumulation, suggesting that iron ions were required for the retinol cellular effects. These findings suggest that retinol-induced DNA damage was associated with the modulation of iron turnover, and these characteristics could be responsible for the increased incidence of lung cancer associated with retinoids supplementation. PMID- 11200100 TI - Aggressive behavior among women sexually abused as children. AB - Although research shows that sexually abused children appear to be at risk of subsequent aggressive behavior, few investigations address whether such behavior persists beyond childhood. This research describes the self-reported adolescent and adult fighting behavior of 136 women sexually abused as children and examines the role of intervening variables in the risk of such behavior. The women are part of a longitudinal study of 206 primarily low-income, urban women whose abuse was documented at the time it occurred. Fighting was common, particularly during adolescence. Adult aggression was strongly associated with being a victim of violence by an intimate partner. A history of exposure to other forms of violence significantly increased the risk of fighting while strong maternal attachments mitigated the risk, primarily by reducing the likelihood of involvement in an abusive intimate relationship. PMID- 11200102 TI - Wife killing: risk to women as a function of age. AB - Younger women, relative to older women, incur elevated risk of uxoricide-being murdered by their husbands. Some evolutionary theorists attribute this pattern to men's evolved sexual proprietariness, which inclines them to use violence to control women, especially those high in reproductive value. Other evolutionary theorists propose an evolved homicide module for wife killing. An alternative to both explanations is that young women experience elevated uxoricide risk as an incidental byproduct of marriage to younger men who commit the majority of acts of violence. We used a sample of 13,670 uxoricides to test these alternative explanations. Findings show that (a) reproductive-age women incur an elevated risk of uxoricide relative to older women; (b) younger men are overrepresented among uxoricide perpetrators; and (c) younger women, even when married to older men, still incur excess risk of uxoricide. Discussion examines competing explanations for uxoricide in light of these findings. PMID- 11200101 TI - The relative frequency of offensive and defensive gun uses: results from a national survey. AB - Some controversy exists about the relative frequency of criminal and self-defense gun use in the United States. Using data from a national random-digit-dial telephone survey of over 1,900 adults conducted in 1996, we find that criminal gun use is far more common than self-defense gun use. This result is consistent with findings from other private surveys and the National Crime Victimization Surveys. In this survey, all reported cases of criminal gun use and many cases of self-defense gun use appear to be socially undesirable. There are many instances of gun use, often for intimidation, that are not reported to the police and may not appear in official crime statistics. PMID- 11200103 TI - Coping with chronic community violence: the variety and implications of women's efforts. AB - To date, most researchers concerned with chronic community violence have studied children, and focused on the types, extent, and effects of their violence experiences. In contrast, using a series of in-depth repeated interviews, the current study explored African American women's methods for coping with chronic community violence. This article describes the variety of ways these women developed to avoid, minimize, or manage their own and their children's encounters with community violence. It argues for the importance of using these data to inform professional intervention and suggests specific implications for practice, program development, and policy. PMID- 11200104 TI - Abuse during and before pregnancy: prevalence and cultural correlates. AB - This study examined the prevalence of abuse during pregnancy and the influence of cultural norms and acculturation on abuse in 1,004 Mexican American, Puerto Rican, Cuban American, Central American, African American and Anglo American women. Women were recruited from consecutive delivery logs in general community hospitals in Florida and Massachusetts. The Index of Spouse Abuse and the Abuse Assessment Screen ascertained history of adult physical, sexual, and emotional abuse, abuse during pregnancy, and childhood sexual abuse. An Interview Protocol assessed cultural attitudes, acculturation, and demographic information. Hispanic American women, as a whole, did not differ significantly from Anglo American women in their prevalence of abuse during pregnancy, after controlling for sociodemographic variables. However, Cuban American and Central American partners were significantly less likely to abuse their pregnant partners than were other groups even after adjustment. Women who spoke only Spanish (less acculturated) were less likely to report physical abuse from their partners both before and during pregnancy. Cultural norms, such as a partner's belief in wife/mother role supremacy and cultural group acceptability of men hitting women, were significantly positively related to both physical and emotional abuse. Other risk factors for abuse were the abuser not being the biological father of the baby, low income and little education, and being unmarried. PMID- 11200105 TI - Women's fear of crime: the role of fear for the well-being of significant others. AB - A number of explanations have been suggested in the literature for the finding that women consistently report higher levels of fear of crime than males. The "shadow" hypothesis argues that fear of crime among females reflects fear of sexual assault. The "intimate" hypothesis argues that women's fear of crime is the result of exposure to intimate violence. Females' fear of crime is expected to be explained by their fear of partners' violence. The main argument of this article is that women's fear of crime might be the result of traditional family gender roles. When asked, women might express fear not only for their own well being but for that of their children. A survey of a representative sample of women in the third largest city of Israel was used to test this assumption. Women's fear of crime was found to be affected by fear of sexual assault and fear of violent partners. In addition, consistent with the argument of this study, women's fear of violent and sexual victimization of their children had a significant effect on their perception of fear. Future directions for research are suggested. PMID- 11200106 TI - Anger, irrational beliefs, and dysfunctional attitudes in violent dating relationships. AB - The purpose of the present investigation was to evaluate whether perpetrators of dating violence could be differentiated from their nonviolent counterparts on measures of anger and cognitive distortion, specifically Ellis's (1994) irrational beliefs and Beck's (1976) dysfunctional attitudes. Of the 95 male and 152 female undergraduates surveyed, 27% (24 males and 43 females) reported using some form of physical aggression against their current dating partner in the past year. On a self-report measure of anger (State-Trait Anger Expression Inventory), violent individuals reported higher levels of Anger Out and lower levels of Anger Control compared to nonviolent participants. While there were no differences between violent and nonviolent participants' levels of Trait Anger, the results suggest that violent individuals have difficulty controlling angry feelings when they arise, which may increase the likelihood of externally directed forms of anger expression. No significant group differences emerged on questionnaire measures of irrational beliefs and dysfunctional attitudes. Within the violent sample, there was no differential pattern of correlations between measures of anger and cognition relative to the nonviolent sample. The present data suggest that while trait-based measures of cognitive distortion explain little variance in self-reported acts of dating violence, future research should investigate whether (a) cognitive distortions are present during affect-inducing partner conflict situations, or (b) vary with violence severity. PMID- 11200107 TI - [Radiation therapy after mastectomy--interdisciplinary consensus puts and end to a controversy. German Society of Senology]. AB - BACKGROUND: Recent publications of the Danish Breast Cancer Cooperative Group together with data from the British Columbia Trial have stirred major discussions concerning the role of radiation therapy after mastectomy. Different treatment approaches are to be found even within the same cancer center. The German Society of Senology, a cooperative group of all medical disciplines involved in the treatment of breast cancer, has therefore worked out a consensus statement. MATERIAL AND METHOD: The recently published literature and experts opinions, in particular randomized studies since 1997, meta-analyses from the Early Breast Cancer Trialists' Collaborative Group, epidemiological investigations with regard to the time course of distant metastases in breast cancer as well as the current consensus of the American Society for Therapeutic Radiology and Oncology served as the basis for discussion and consulting. RESULTS OF THE CONSENSUS: (1) An optimally performed mastectomy is a major prerequisite for tumor cure. Radical (R0) resection of the tumor as well as dissection of at least 10 lymph nodes from the axillary level I and II should be accomplished. If axillary lymph nodes are involved, the surgical removal of these lymph nodes is not only of diagnostic, but also of therapeutic value, as it reduces the risk for locoregional relapses. (2) Most probably, locoregional relapses do not only indicate, but are also a source for distant metastases. (3) Radiation therapy of the chest wall and the regional lymph nodes increases the overall survival in risk patients and reduces the risk of locoregional relapses. Moreover, radiation therapy improves the prognosis in case of residual tumor or an incomplete axillary dissection. Unequivocal and reasonable indications for radiation therapy after mastectomy include T3/T4-carcinoma, T2-carcinoma > 3 cm, multicentric tumor growth, lymphangiosis carcinomatosa or vessel involvement, involvement of the pectoralis fascia or a safety margin < 5 mm, R1- or R2 resection and more than 3 axillary lymph node metastases. Further reasonable indications, albeit not yet evaluated in clinical trials, include multifocality, extensive intraductal component, negative hormone receptor status, G3-differentiation grade, diffuse micro calcifications, 1 to 3 axillary lymph node metastases, multiple, non-complete biopsies and age < 35 years. (4) An endocrine therapy with tamoxifen concurrent to radiation therapy is also reasonable--despite some contradictory in-vitro data -as it enhances the apoptotic cell death. The CMF-regimen is usually performed as sandwich procedure, but can also be applied concurrently to radiation therapy, if indicated. Conversely, an anthracycline-containing chemotherapy should be finished prior to postoperative radiation therapy. CONCLUSIONS: Adjuvant radiation therapy after mastectomy improves the 10-year-survival probability up to 10%, at least for risk patients. The hypotheses of Halsted and Fisher do not exclude each other. There are patients, in which the one, and there are patients, in which the other hypothesis applies. PMID- 11200108 TI - [A model for primary and secondary metastasis in breast cancer and the clinical consequences]. AB - BACKGROUND: An adjuvant locoregional radiotherapy after radical surgery results in a survival advantage for breast cancer patients. The advantage starts with a delay and reaches about 10% 15 years after diagnosis. What could explain such a delayed efficacy? METHODS: A population-based cohort from 1996 to 1998 and the Munich Cancer Registry with courses of breast cancer disease since 1977 are the empirical basis. The analysis concerns survival rates and survival times in respect to metastases, local and lymph node recurrencies. A metastatic model is derived from the data. RESULTS: A cohort of 9,347 patients with a mean follow-up of 6.5 years and 2,587 courses with metastases and/or local recurrencies were registered. The overall survival after 15 years was for pT1 57.6%, pT2 37.9%, pT3 24.4% and for pT4 10.5%. Five years after metastasization 20.1 to 12.4% survived, 10 years 6% independent on pT. Ten years after local recurrencies the survival was dependent on pT of the primary tumor: pT1 36.3%, pT2 21.0%, pT3 13.1% und pT4 4.6%. A local recurrency is a prognostic factor for metastasization of the primary tumor, but local recurrencies can also cause metastases. The mean survival time after metastasization of the primary pT1 tumor is estimated about 61 months, after metastasization by local recurrencies about 99 months with a mean time to local recurrencies of 38 months. Further results of the metastatic model are: the development of metastasization is homogeneous and independent on pT-category, the metastatic initiation starts up to 5 years before diagnosis, metastatic-free survival time and progression survival time are independent and an impact of lymph node recurrencies on survival could not be detected. CONCLUSIONS: The reduction of local recurrencies by high-quality primary therapy with radiotherapy and also the early detection of local recurrencies may reduce secondary metastasization and therefore improve survival. The metastasization model also explains the limitation of the therapeutical strategies and the almost mandatory chance of early detection programs of breast cancer. PMID- 11200109 TI - [Local tumor control and cosmetic outcome following breast-conserving surgery and radiation up to a total dose of 56 Gy without boost in breast cancer]. AB - PURPOSE: To evaluate overall survival, local tumor control and cosmetic outcome after breast-conserving surgery followed by radiotherapy without boost irradiation. PATIENTS AND METHODS: In a retrospective study 270 breast cancer patients were treated with breast conserving surgery combined with a homogenous radiation of the tumor bearing breast up to a total dose of 56 Gy without local boost irradiation. Mean follow-up was 48 months. Local tumor control, side effects, cosmetic results and contentment with treatment were assessed using physical examinations and interviews based on a standardized questionnaire. RESULTS: Cause-specific survival at 5 years after treatment was 88.3%, actuarial disease-free survival at 5 years was 76.1%. Within 23 to 78 months after treatment 12 patients suffered from ipsilateral breast recurrence. The actuarial freedom from local recurrence (single tumor manifestation) was 96.8% at 5 years after treatment, 89% at 10 years. The occurrence of local failures was not significantly correlated to tumor size, margins, grading, nodal status, age or lymphangiosis. 15.6% of the patients developed distant metastases. In all patients treatment was performed without interruption. Side effects were predominantly of mild degree, no severe side effects were detected. 73% of physicians and 81% of patients scored their cosmetic outcome as excellent or good. 93% of patients would again decide in favor of this procedure. Whereas use of adjuvant chemotherapy as well as subcutaneous reconstruction of breast tissue did not significantly affect breast cosmesis, analysis demonstrated impaired cosmetic results related to a larger breast size. CONCLUSION: The data of this study show that tumor control achieved by breast conserving surgery in combination with a radiation technique up to a total dose of 56 Gy which omits boost irradiation is within the range of literature data. Side effects of the therapy were tolerable. The treatment displayed a good compatibility with tolerable side effects and good cosmetic results. PMID- 11200110 TI - Which patients don't need a tumor-bed boost after whole-breast radiotherapy? AB - BACKGROUND: Retrospective dose-response data suggest that a boost of about 15 Gy to the tumor bed following whole-breast radiotherapy reduces the risk of local recurrence (IBTR) by as much as 2-fold. Even if this benefit is confirmed by prospective trials, boost irradiation may not be considered cost-effective in patients having an IBTR risk of less than 1% per annum. METHODS: Published prospective trials of invasive breast cancers (National Surgical Adjuvant Breast and Bowel Project; Stockholm Adjuvant Tamoxifen Trial) in which patients received 50 Gy whole-breast irradiation, without a boost, were analyzed to identify subgroups with IBTR risk less than 1% per year. All studies were based on lumpectomy (rather than segmental or quadrant excision) and eligibility required the absence of cancer cells at the margins. It was assumed that clinical and pathological factors, other than those defining trial eligibility, were of negligible importance regarding IBTR risk, with the exception of young age. RESULTS: All patients not receiving adjuvant systemic therapy, including tumors < 1 cm, have IBTR risk justifying boost irradiation. Of patients receiving systemic therapy, only patients with node-negative, estrogen receptor-positive tumors have low IBTR risk (3% at 10 years), provided that tamoxifen is administered. Of patients receiving only adjuvant chemotherapy, low IBTR risk seems to be associated with administration concomitantly with radiotherapy. IBTR risk in patients receiving chemotherapy sequentially with respect to radiotherapy probably is high enough to justify a boost. A boost is probably indicated in all patients younger than 40 years, regardless of other factors. PMID- 11200111 TI - Determination of tolerance dose uncertainties and optimal design of dose response experiments with small animal numbers. AB - BACKGROUND: Dose response experiments aim to determine the complication probability as a function of dose. Adjusting the parameters of the frequently used dose response model P(D) = 1/[1 + (D50/D)k] to the experimental data, 2 intuitive quantities are obtained: the tolerance dose D50 and the slope parameter k. For mathematical reasons, however, standard statistic software uses a different set of parameters. Therefore, the resulting fit parameters of the statistic software as well as their standard errors have to be transformed to obtain D50 and k as well as their standard errors. MATERIAL AND METHODS: The influence of the number of dose levels on the uncertainty of the fit parameters is studied by a simulation for a fixed number of animals. For experiments with small animal numbers, statistical artifacts may prevent the determination of the standard errors of the fit parameters. Consequences on the design of dose response experiments are investigated. RESULTS: Explicit formulas are presented, which allow to calculate the parameters D50 and k as well as their standard errors from the output of standard statistic software. The simulation shows, that the standard errors of the resulting parameters are independent of the number of dose levels, as long as the total number of animals involved in the experiment, remains constant. CONCLUSION: Statistical artifacts in experiments containing small animal numbers may be prevented by an adequate design of the experiment. For this, it is suggested to select a higher number of dose levels, rather than using a higher number of animals per dose level. PMID- 11200113 TI - Irradiation of histiocytosis X confined to the oral mucosa. AB - BACKGROUND: Histiocytosis X is a rare granulomatous disease and it is still under debate as to whether this disease has to be counted among malignant tumors or benign immunologic lesions. The typical localization is confined to the bone. In rare cases histiocytosis X may be localized in the oropharyngeal mucosa. PATIENTS AND METHODS: We report about a case of a 75-year-old woman presenting with histiocytosis X lesions solely located in the oral cavity. A total dose of 19.5 Gy was administered without any side effects. RESULTS: Two weeks after completion of irradiation a rapid regression of mucosal ulcerations and improvement of symptoms occurred. In a follow-up of 24 months the patient is still in complete remission observed. CONCLUSION: Review of the literature revealed only casuistic reports about solitary lesions of histiocytosis X without bone involvement in the adulthood. External beam radiotherapy with total doses between 10 and 20 Gy seems to be effective for local control of this disease. PMID- 11200112 TI - A simple and non-invasive vacuum mouthpiece-based head fixation system for high precision radiotherapy. AB - PURPOSE: To demonstrate why conventional non-invasive mouthpiece-based fixation has not achieved the expected accuracy and to suggest a solution of the problem. PATIENTS AND METHODS: The Vogele Bale Hohner (VBH) head holder is a non-invasive vacuum mouthpiece-based head fixation system. Feasibility and repositioning accuracy were evaluated by portal image analysis in 12 patients with cranial tumors intended for stereotactic procedures, fixated with the newest version (VBH HeadFix-ARC). RESULTS: Portal image analysis (8 patients evaluated in 2-D, 4 patients in 3-D) showed that even in routine external beam radiation therapy, treatment can be applied to within a mean 2-D and 3-D accuracy of under 2 mm (SD 0.92 mm and 1.2 mm, respectively) with cost and repositioning time per patient and patient comfort comparable to that of common thermoplastic masks. CONCLUSION: These preliminary results show that high repositioning accuracy does not rule out simple and quick application and patient comfort. Paramount, however, is tensionless repositioning via the vacuum mouthpiece. PMID- 11200114 TI - [Lobular carcinoma in situ as a component of breast cancer points to no contraindication for breast-conserving therapy]. PMID- 11200115 TI - [Local recurrence in premenopausal women with breast cancer: risk factors and effect of therapy]. PMID- 11200117 TI - Often neglected yet important: the pericardium and its diseases. PMID- 11200116 TI - [No improvement in therapeutic results with neoadjuvant chemotherapy in cervical cancer compaared with radiotherapy alone]. PMID- 11200118 TI - Microphysiology of the pericardium: substrate for intrapericardial therapeutics. AB - Recent capability to enter the normal effusion-free pericardium has expanded intrapericardial therapy which was formerly restricted to patients with effusive pericardial disease, to intrapericardial treatment of cardiac diseases of all kinds. It is now possible to deposit in the intact pericardium a variety of therapeutic agents targeting the myocardium, valves, conduction system and even the endocardium. In addition to such specific agents, the unique microphysiology of the pericardial mesothelium provides investigators with 2 entirely new applications of intrapericardial therapy: 1. supplementing substances like prostanoids and a variety of immune factors, and 2. stimulating pericardial production of such products of metabolism, e.g., superfusion of the normal pericardium by non-steroidal antiinflammatory agents to stimulate prostanoid production with a variety of effects including possible inhibition of coronary thrombosis. Continuing research and development should determine the precise roles of these new applications in human medicine. PMID- 11200119 TI - Morphological considerations of peri- and myocarditis. AB - In medicine, and thus in pathology, there are areas/topics of fashion and they shift from time to time. Pericardial diseases are not fashionable. Myocarditis is, and has been for a long time. Due to new ways of retrieving tissue samples from the pericardium the modern diagnostic tools such as immunohistochemistry and molecular pathology can be applied in this context as they have been in myocarditis for a long period. The diagnosis of inflammation rests on many other findings than morphological alterations and it is indeed questionable if inflammation is solely a morphological diagnosis. The methodologies of pathology can be improved and used in a better and more purposeful way even under routine conditions. It is concluded that morphology is still mandatory to make a final diagnosis of peri- and myocarditis. PMID- 11200120 TI - Arrhythmias in acute pericarditis. An endomyocardial biopsy study. AB - It is still controversial whether the arrhythmias in acute pericarditis are of myocardial or pericardial origin. The aim of the present study was to investigate the occurrence of arrhythmias and conduction disorders in patients with acute pericarditis with no endomyocardial biopsy evidence of myocarditis (group 1: 40 patients, 65% males, mean age 45.6 +/- 15.7 years, mean heart rate [HR] 98.7 +/- 22.2 beats per minute) in comparison to endomyocardial biopsy proven acute myocarditis/perimyocarditis (group 2: 10 patients, 3/10 with perimyocarditis, 70% males, mean age 46.1 +/- 15.8 years, mean heart rate 76.7 +/- 33.1 beats per minute). At the initial assessment all patients underwent comprehensive clinical work-up including echocardiography, cardiac catheterization, and endomyocardial biopsy. In all patients biventricular endomyocardial biopsy was performed using standard femoral approach and Schikumed 7 F or 8 F bioptomes. Tissue samples were stained by H & E, v. Gieson and independently reviewed by two cardiac pathologists. In addition immunohistochemistry and immunocytochemistry were performed, and only patients fulfilling Dallas and World Heart Federation criteria were selected for group 2. Comparative analysis of electrocardiograms and 24-hour Holter recordings at initial presentation revealed in group 1 vs group 2 significantly less frequent paroxysmal supraventricular tachyarrhythmias (5% vs 40%), and ventricular fibrillation (0 vs 20%), in contrast to atrial fibrillation that occurred more often (20% vs 0) (all p < 0.05). Furthermore, in the group 2 one patient died due to VF and two patients underwent ICD implantation. Low voltage (40% vs 30%) and ST/T wave changes (47.5% vs 30%), as well as the incidence of the II degree AV block (5% vs 0) and complete AV block (2.5% vs 10%) were not significantly different between the groups. In conclusion, patients with pericarditis and no endomyocardial biopsy indications of myocarditis had significantly less often life threatening rhythm disorders in contrast to patients with endomyocardial biopsy proven acute myocarditis/perimyocarditis. On the contrary, incidence of transitory atrial fibrillation was higher in acute pericarditis, than in myocarditis. PMID- 11200121 TI - Diagnostic value of echocardiography in cardiac tamponade. AB - Cardiac tamponade is a life-threatening condition. Accurate diagnosis and prompt intervention are necessary to prevent adverse outcomes. Clinical features of tamponade such as pulsus paradoxus, tachycardia, elevated jugular venous pressure, and hypotension are important clues to the diagnosis, but are non specific. Echocardiography allows rapid confirmation of the presence or absence of an effusion, and enables assessment of its hemodynamic impact. Decisions regarding treatment must take into account the clinical presentation and echocardiographic findings. Echocardiographically-guided pericardiocentesis with catheter drainage is the primary treatment strategy of choice for most large or hemodynamically significant effusions. In contemporary clinical practice, echocardiography is the gold standard for diagnosis of tamponade and is essential for directing treatment. PMID- 11200122 TI - Flexible percutaneous pericardioscopy: inherent drawbacks and recent advances. AB - Pericardioscopy enables endoscopic inspection and aimed biopsy of the parietal and visceral pericardium. To elucidate possible technical modifications contributing to the feasibility, diagnostic value and safety of the procedure, pericardioscopy with an Olympus HYF-1T flexible endoscope was performed in 32 patients (53.1% males, mean age 46.2 +/- 13.1 years) with pericardial effusions. In all patients, the initial step of the procedure was subxiphoid fluoroscopically controlled pericardiocentesis and drainage of the pericardial effusion. An Olympus FB-41ST biopsy forceps was applied for endoscopically guided pericardial biopsies. Standard sampling was used in 22/32 patients (3 to 6 samples/patient) and extensive sampling in 10/32 patients (18 to 20 samples/patient). In additional 12 patients pericardial biopsy was performed without pericardioscopy, under fluoroscopic control. Endoscopic visualization was clearly superior when pericardial effusion was partially replaced with 100 to 300 ml of air (29/32 procedures) in comparison to 3/32 procedures in which the pericardial effusion was replaced with warm normal saline (37 degrees C). In patients with hemorrhagic effusion (12/32), we either repeatedly injected and removed 100 to 150 ml volumes of normal saline (37 degrees C), or postponed pericardioscopy for 2 to 3 days of active drainage. The specificity of endoscopic findings is low and not decisive for the diagnosis. However, pericardioscopy is significantly contributing to the diagnostic value of pericardial biopsy, especially regarding establishing the new diagnosis and etiology of the pericardial disease. Sampling efficiency was also significantly higher for procedures using aimed pericardial biopsy with standard and extensive sampling compared to procedures performed under fluoroscopy: 86.2%, 87.3%, and 43.7%, respectively. No major complications directly related to the procedure were encountered. Minor complications included: short-run ventricular tachycardia (6.3%), pain at the sheath entry site (75%) and transient fever (37.5%). In conclusion, pericardioscopy with Olympus HYF-1T, after air instillation, is a technically complex, but safe procedure that enables excellent visualization and extensive pericardial sampling with improved diagnostic value of pericardial biopsies. PMID- 11200123 TI - Cytokine activation in pericardial fluids in different forms of pericarditis. AB - There are many causes of pericardial effusion and it is useful to classify them etiologically, since this disorder is the most common pathologic process involving the pericardium. This report details our experience with pericardioscopy and epicardial biopsy in 101 patients with pericardial effusions in whom pericardioscopy was performed. By means of clinical data and polymerase chain reaction we tried to elucidate the etiology of the pericardial effusion which were classified as follows: we found 41 effusions to be induced by primary malignant tumors or tumors metastatic to the pericardium. Specific diagnosis of viral and bacterial pericarditis was established in 17 patients by examination of the pericardial effusion with PCR, where we found 3 patients positive for adenovirus, 5 patients positive for cytomegalovirus, 2 patients positive for enterovirus-RNA and 5 patients positive for borrelia Burgdorferi-DNA. Additionally, idiopathic effusions (lymphocytic and autoreactive) were seen in 35 patients. In summary immunological and molecular biology investigations seem to provide an additional tool in the diagnostic of pericardial effusion with unknown etiology. If we focus on the ELISA results, there is some evidence, that the demonstration [table: see text] of activation markers and soluble mediators of inflammation such as Il-6, Il-8 and IFN-gamma in pericardial effusion and the simultaneously lack of these mediators in sera of the patients first may be helpful in the discrimination of autoreactive and lymphocytic effusion. Second, this cytokine pattern or distribution indicates a possible local inflammatory process, where these cytokines were all released from activated T lymphocytes present in lymphocytic effusion. In the future, this may have therapeutic implications. PMID- 11200124 TI - [Contrast medium echocardiography-assisted pericardial drainage]. AB - The most effective treatment for pericardial effusion and cardiac tamponade is removal of the pericardial fluid. Surgical pericardiotomy is associated with high mortality and morbidity. Similarly, subcostal percutaneous blind pericardiocentesis was reported to have unacceptably high mortality and complication rates. Major complications associated with blind needle punctures are right heart penetration, hemopericardium, puncture of the coronary arteries, liver and lung bleeding. Even under fluoroscopic guidance and electrocardiographic needle monitoring high complication rates persist. Pericardial drainage has been often inadequate, with frequent recurrences of significant pericardial effusions. Two-dimensional echocardiographically guided pericardiocentesis is reported to improve efficacy and safety of percutaneous puncture. Moreover, it allows immediate verification of the procedural success. We evaluated the efficacy and safety of an echocardiographically guided contrast agent controlled pericardiocentesis. This is a retrospective, descriptive study on 126 consecutive patients who underwent percutaneous pericardiocentesis at the University Hospital Essen, Germany, from 1995 to June 2000. There were 51 women (41%) and 75 men (55%) with a mean age of 52 +/- 14 years. Standard techniques for quantification of pericardial effusion were used. Depending on the localization of the pericardial effusion an apical or subxiphoidal approach was chosen. The puncture was performed under echocardiographic guidance and the position of the needle was controlled by injection of contrast agent. Over a long guidewire a pigtail catheter was inserted through a sheath for further drainage of pericardial fluid. The catheter was removed after a maximum of 48 hours to avoid infection of the pericardial cavity. An apical approach was chosen in 98 patients (78%), a subcostal in 28 patients (22%). The procedure was successful in 99% of the attempts. No death or clinical complication occurred. The maximal pericardial diameter measured by two-dimensional echocardiography was 32 +/- 16 mm before and 5.3 +/- 2 mm after drainage. The calculated pericardial effusion was 657 +/- 342 ml. A fluid volume of 605 +/- 342 ml could be drained. In all patients a pericardial catheter was placed for 1.4 +/- 0.8 days. Recurrence of pericardial effusion occurred in 18 patients (14%). Of these, 15 patients underwent repeated successful pericardiocentesis (2.5 +/- 0.8), and 3 patients were referred to surgical pericardiotomy. Pericardiocentesis under echocardiographic contrast agent guidance is a safe, successful and cost effective procedure for diagnostic and therapeutic drainage of pericardial effusion. Two-dimensional echocardiography allows localization of the optimal puncture site as well as the quantification of the effusion depth. The injection of contrast agents into the pericardial cavity improves the safety and accuracy of the procedure. Even recurrent pericardial effusions can be treated successfully. PMID- 11200125 TI - Computer-guided pericardiocentesis: experimental results and clinical perspectives. AB - Percutaneous pericardial puncture is a relatively safe and effective technique in case of large pericardial effusions when practiced under echographic or radiological control. The goal of our project is to improve the performance of this technique, mainly in case of smaller and loculated effusions using an accurate guidance towards a preplanned target, based on a model of the pericardial effusion. This paper presents preclinical results of this new computer-assisted technique used to reach the pericardial cavity. The procedure is divided into 3 steps: 1. acquisition of ultrasound data, using an echocardiographic device connected to a 3-D localizer and to a computer, 2. modeling procedure to define the optimal strategy taking into account the mobility of organs on a digital model, 3. guided puncture with a localized needle to reach the predefined target using a passive guidance system. After validation on a dynamic phantom and a feasibility study on dogs, an accuracy and reliability analysis protocol was realized on pigs with experimental pericardial effusion. Feasibility of the technique is demonstrated on animal study with an accuracy of at least 2.5 mm. Further clinical investigation is in progress using a more ergonomic and less cumbersome system. This study demonstrates the feasibility of computer-assisted pericardiocentesis. Beyond the simple improvement of the current technique, this could be a new way to reach the heart or a new tool for percutaneous access and image-guided puncture of soft tissues. PMID- 11200126 TI - New directions in diagnosis and treatment of pericardial disease. A project of the Taskforce on Pericardial Disease of the World Heart Federation. AB - New directions in the diagnosis and treatment of pericardial diseases synthesize the achievements of modern imaging with molecular biology and immunology techniques. Comprehensive and systematic implementation of new techniques of pericardiocentesis, pericardial fluid analysis, pericardioscopy, epicardial and pericardial biopsy, as well the application of comprehensive molecular biology and immunology techniques for pericardial fluid and biopsy analyses have opened new windows to the pericardial diseases, permitting early specific diagnosis and creating foundations for etiologic treatment in many cases. In patients with recurrent pericarditis, resistant to conventional treatments, as well as in patients with neoplastic pericarditis an alternative intrapericardial treatment regimen was suggested by the Taskforce on Pericardial Diseases of the World Heart Federation. Intrapericardial application of medication avoids systemic side effects with increased local efficacy. The following protocols are proposed: CIRP (colchicine in recurrent pericarditis)--colchicine vs placebo in chronic/recurring pericarditis without pericardiocentesis; TRIPE (triamcinolone in pericardial effusion)--intrapericardial instillation of triamcinolone + 6 months colchicine vs pericardial puncture without instillation + 6 months colchicine; NEPIN (neoplastic effusion and pericardial instillation)- pericardiocentesis and drainage + intrapericardial instillation of cisplatin or thiotepa. PMID- 11200127 TI - Intrapericardial treatment of autoreactive myocarditis with triamcinolon. Successful administration in patients with minimal pericardial effusion. AB - A major clinical drawback in the treatment of autoreactive pericarditis is its inherent feature to relapse. Intrapericardial treatment with triamcinolone was reported to be efficient in patients with large, symptomatic autoreactive pericardial effusions, avoiding side effects of systemic treatment as well as compliance problems. Intrapericardial treatment with 300 mg/m2 triamcinolone was for the first time performed in patients with autoreactive myopericarditis and minimal pericardial effusions (75 to 110 ml). After 12 months of follow-up both patients are asymptomatic and there were no further recurrences of pericardial effusion. Pericardiocentesis in these patients was performed with the application of the PerDUCER device, guided by pericardioscopy. This device has a hemispherical cavity at the top of the instrument connected with a vacuum producing syringe. In this cavity the pericardium is captured by vacuum and tangentially punctured by the introducer needle. Pericardium that can be captured, must be up to 2 mm thin to fit into the hemispherical cavity. Pericardioscopy performed from the anterior mediastinum significantly contributed to the success of the procedures enabling visualization of the portions of the pericardium free of adipose tissue or adhesions, suitable for puncture with the PerDUCER. In conclusion, intrapericardial treatment of symptomatic autoreactive myopericarditis with minimal pericardial effusion was safely and efficiently performed in 2 patients. Pericardiocentesis was enabled by means of the PerDUCER device, facilitated by pericardioscopy. PMID- 11200128 TI - Intrapericardial treatment of neoplastic pericardial effusions. AB - Pericardial effusion and cardiac tamponade are known complications of many advanced malignancies as lung cancer, breast cancer, lymphomas and leukemias. Initial relief can be easily obtained with percutaneous echo-guided pericardiocentesis, without significant mortality and morbidity and well tolerated even in critically ill patients. Effusion recurrences can be observed, however, in up to 40% of cases if only simple pericardial drainage is performed. Effective management can be obtained by instillation in the pericardial sac of different agents, with sclerosing or cytostatic activity, like tetracyclines, bleomycin, thiotepa or radionuclides. Intrapericardial sclerotherapy is associated to good results in terms of recurrence prevention and survival improvement. Absence of pericardial effusion at 30 days after drainage can be observed in 70 to 90% of all treated patients, without significant variations among different treatments. No significant side effects are observed, with the exclusion of chest pain during tetracyclines instillation. In our opinion pericardiocentesis associated to intrapericardial sclerotherapy with thiotepa is the best compromise in terms of recurrence prevention, tolerability and costs. Real randomized, case-control studies are moreover required to assess the gold standard of malignant pericardial effusions treatment. PMID- 11200129 TI - Indications, results, and pitfalls in the surgery of constrictive pericarditis. AB - Constrictive pericarditis is a rare disease with an often unclear etiology. There may be a long delay between the onset of the underlying disease and the onset of clinical symptoms, which are fatigue, abdominal swelling, peripheral edema and breathlessness. However, if clinically apparent, these symptoms may progress rapidly and severely disable the affected patient. Diagnosis is achieved by the clinical presentation, echocardiography and/or MRI and right heart catheterization. The standard therapy is an extended pericardiectomy to restore an unlimited inflow and outflow as well as an unrestricted diastolic function of both ventricles. The risks of this procedure are related to dense adhesions between the 2 pericardial layers and severe calcifications especially of the epicardium. Incomplete removal results in persistent diastolic restriction while lacerations of the underlying myocardium may lead to diffuse and extensive bleeding and finally to myocardial dysfunction. Also, the postoperative course may be complicated by persistent low output syndrome or acute ventricular dilatation. However, early surgical intervention in the hands of experienced surgeons offers the best prognosis. PMID- 11200130 TI - Assessment of the national communicable disease surveillance and response system, Ethiopia. PMID- 11200131 TI - [Effect of ectopic superexperssion of the anti-apoptotic gene bcl-2 on the level and character of karyotypic instability in the CHLL V-79 RJK Chinese hamster cell line]. AB - Karyotypic destabilization in cells of Chinese hamster fibroblasts CHL V-79 RJK with ectopically overexpressed antiapoptotical human bcl-2 gene from pSFFV-bcl-2 vector has been analysed. Analysis of G-banded metaphase chromosomes from 4 clones with different levels of bcl-2 expression revealed an increased level of chromosomal instability in bcl-2-transfected cells. Besides, an increased percentage of aneu- and polyploid cells and high level of cells with different chromosomal aberrations was observed. The degree of karyotypic instability positively correlated with the level of bcl-2 expression in bcl-2-transfected cells. Cells of a clone with the highest bcl-2 expression at the 13th passage of cultivation displayed an almost 100% polyploidization and the presence of specific aberrations and a tricentric marker chromosome. Selection of cells with non-random specific chromosome changes was observed in pSFFV-bcl-2-transfected CHL V-79 RJK cells in the process of their long-term cultivation. By contrast, cells of the parental cell line, as well as the control pSFFV-neo transfectants, displayed a stable karyotype throughout the long period of cultivation. It is important that the presence of morphological markers of gene amplifications--DOO, DM, MH--was observed in bcl-2-transfected cells. These findings suggest that the overexpression of antiapoptotic human bcl-2 gene may result in destabilization of the karyotype structure in cells of Chinese hamster fibroblasts CHL V-79 RJK. The character and level of destabilization correlate with the level of ectopic overexpression of this gene. PMID- 11200132 TI - [Interaction of tumor cell differentiation induced in vitro and sensitivity of them to nonspecific lysis by natural killer cells. Possible mechanisms]. AB - The literature data on the influence of a large group of cancer cell differentiation inducers on the modulation of their susceptibility to non-MHC restricted lysis (non-specific cytotoxicity, NCT) by natural killer (NK) cells have been analysed. A possible association between the apoptogenic action of differentiation inducers and their ability to modulate the NCT of cell targets by NK cells is discussed. PMID- 11200133 TI - [Morphogenesis and formation of a pattern in hydra. I. Distribution of morphogenetic potential]. AB - True multicellularity is characterized by complex interactions between individual cells of the organism as well as by organization of cell masses into spatially and functionally determined structures promoting the exchange of information. Morphogenetic processes--genetically programmed generation of structures--always correlate with determination and maintenance of a pattern, i.e. a system of spatial relationships between them. Hydroid polyps provide a wide variety of approaches to study morphogenesis and patterning. Being comparatively simply organized, these animals have nevertheless certain developed mechanisms underlaying such processes as regeneration of missing structures, recovery of normal pattern after dissociation of polyps into single cells, tissue transdifferentiation in non-complementary chimaeras. An important feature of regeneration of hydroid polyps is its independence of the nerve net elements; the basis for regeneration is rather stored in epithelial cells and in their interactions. Phenomenological data, provided in the XVIII-XX centuries, allowed to propose several theoretical models of pattern regulation in hydra. The main goal of this paper is to review contemporary models of morphogenesis and patterning in the hydroid polyps. PMID- 11200134 TI - [Analysis of the proliferative activity of a cell using new monoclonal antibodies to nucleolar protein B23/nucleophosmin]. AB - Nowadays, antinucleolar antibodies are widely used for exploration of the nucleolar organization and molecular mechanisms of ribosome production. Here we have described a new monoclonal antibody against the major nucleolar phosphoprotein B23/nucleophosmin (3C9) that is involved in the terminal stages of ribosome production. It is used to examine immunocytochemical peculiarities of the nucleolus in terms of the cell proliferative status and also during mitosis. In human peripheral blood lymphocytes, activated for proliferation with phytohaemagglutinin (PHA), PHA stimulation of lymphocytes was shown to result in accumulation of protein B23 in augmentative nucleoli. A comparative study of 3C9 and two other anti-B23 antibodies 20B2 and anti-B23 by Western blots and indirect immunofluorescence favored the idea that 3C9 cross-reacted with the major isoform of B23, B23.1, that have an apparent molecular weight of 40 kDa. PMID- 11200135 TI - [Differentiated murine F9 teratocarcinoma cells are susceptible to apoptosis upon contact with substrate]. AB - Epithelial and endothelial cells are susceptible to a subset of apoptosis known as anoikis. This type of programmed cell death is activated upon disruption of cell-substrate contacts. Here we demonstrate that mouse F9 embryonal carcinoma cell line acquires susceptibility to anoikis upon retinoic acid-induced differentiation towards non-malignant pariental endoderm-like cells. F9 cells survival becomes dependent on the substrate by the 4th day of retinoic acid treatment, when cells assume epithelial phenotype as revealed by actin, alpha actinin and vinculin expression and distribution, and when focal adhesion contacts are formed. Differentiated F9 cells die in suspension by apoptosis as revealed by oligonucleosomal DNA laddering, DAPI staining and DNA flow cytometry analysis. On the contrary, undifferentiated F9 cells form large multicellular aggregates in suspension and survive. Thus, F9 cell line provides a new model to study pathways involved in both anoikis induction and inhibition. PMID- 11200136 TI - [Cleavage of DNA-binding loops of actin by subtilisin prevent formation of a strong type of myosin binding with actin]. AB - In order to elucidate the role of DNA-binding loop of actin (amino acid residues 38-52) in mechanisms of muscle contraction, polarizational fluorimetry and ghost muscle fibers, containing thin filaments reconstructed by intact and subtilisin cleaved G-actin were used. The thin filaments were modified by fluorescent probes rhodamin-phalloidin and 1,5-IAEDANS. Changes in orientation and mobility of the probes were considered as an indication of changes in actin conformation. The stage AM of ATP hydrolysis cycle was simulated. For this purpose, thin filaments were decorated by myosin subfragment-1 (S1) in the absence of nucleotide. It has been shown that S1 binding to actin is accompanied by changes in orientation and mobility of the fluorescent probes. For intact filaments, the changes of these parameters indicate the formation of a strong binding between S1 and actin. Cleavage of DNA-binding loop by subtilisin markedly inhibits this effect. The cleavage of actin by subtilisin has also been shown to diminish the changes in fiber birefringence, which takes place at the formation of F-actin-S1 complex in the muscle fiber. The spatial organization of the actin DNA-binding loop is suggested to play an important role in determining the character of myosin interaction with actin in the ATP hydrolysis cycle. PMID- 11200137 TI - [Long-term action of vitamin D suppresses the estradiol-induced activity of erk-1 MAPK and proliferation of MCF-7 and LNCaP cancer cells]. AB - A study was made of the influence of a long-term exposure of 1,25 dihydroxyvitamin D3 and 17 beta-estradiol on deactivation of MAP kinases in correlation with proliferation of cancer cells. The obtained results illustrate inhibition of cell growth after vitamin D treatment. Mechanisms of such an inhibition are discussed. PMID- 11200139 TI - Proceedings of the British Pharmacological Society Meeting. 6-8 September 2000, University of Bradford. Abstracts. PMID- 11200138 TI - [Ultrastructural characteristics of rat neuromuscular junctions after physical load]. AB - It is interesting to ascertain the adaptive reaction of rat neuromuscular junctions (NMJ) of muscle fibers of different types to a chronic physical load. We examined ultrastructural changes in NMJ following both static load (pre- and postnatal ontogenesis of Wistar rats till a 2 month age took place under a constant rotation on the centrifuge at hypergravity conditions 2G), and after three kinds of dynamic loads (1/run on treadmill with a speed 35 m/min for 6 wks, 10-60 min/day; 2/swimmings, each 10 hrs/day for 10 days; 3/strength exercises on a vertical treadmill with load for 6 wks). Differences in NMJ reaction of muscle fibers of the same type to various loads were established. A low secretory activity of axonal terminals of type I muscle fibers of m. soleus was shown after the static load. The dynamic load (run) is accompanied with a high secretory activity of axonal terminals in m. soleus type I muscle fibers and of some axonal terminals of m. quadriceps femoris IIB type muscle fibers after strength exercises; the secretory activity of axonal terminals of m. quadriceps femoris IIA and IIB types muscle fibers is expressed in a lesser degree after swimming. The NMJ ultrastructure remodelling (terminal renewal) of type I muscle fibers of the 2 month old control rats increases after static and dynamic (run) loads. Some correlations between different kinds of physical load, muscle fiber type and the degree of NMJ ultrastructure transformation have been shown. PMID- 11200140 TI - Statistics and analysis of the Camino ICP monitor. PMID- 11200141 TI - 21st Annual Meeting of the Society for Maternal-Fetal Medicine. February 5-10, 2001. Reno, Nevada, USA. Abstracts. PMID- 11200142 TI - The evolving role of irinotecan: a broad-spectrum chemotherapeutic agent. Introduction. PMID- 11200143 TI - Irinotecan and cisplatin in advanced gastric or gastroesophageal junction carcinoma. AB - Chemotherapy for advanced gastric and gastroesophageal junction carcinomas remains suboptimal. Both irinotecan (Camptosar) and cisplatin (Platinol) are active against this group of malignancies. This article focuses on the results of an ongoing phase II trial with this combination in patients with advanced gastric or gastroesophageal junction carcinoma. Data from this trial suggest that the combination of irinotecan and cisplatin is active in untreated as well as previously treated patients with gastric or gastroesophageal junction carcinoma. PMID- 11200144 TI - Developments in the treatment of gastric cancer in Europe. AB - Metastatic gastric cancer is a relatively chemosensitive disease. With current regimens, 25% to 40% of patients can be expected to respond, and median survival of 6 to 8 months is achievable. These outcomes may be improved by the use of infusional fluorouracil (5-FU) in combination with cisplatin (Platinol) or the newer agents docetaxel (Taxotere) and irinotecan (Camptosar). Phase II studies using these approaches have reported response rates of 50% to 60% and median survival of 11 months. Chemotherapy may also have a role in earlier stages of gastric cancer. However, the value of adjuvant therapy in improving survival following successful resection has still to be demonstrated, as has the survival benefit of preoperative treatment. Nevertheless, primary chemotherapy has demonstrated a capacity to downstage disease in certain otherwise inoperable cases. PMID- 11200145 TI - Irinotecan in esophageal cancer. AB - Irinotecan (Camptosar) has shown activity in several solid tumor malignancies, including gastric and pancreatic cancer. In vitro studies suggest antitumor activity in esophageal cancer cell lines. Sequence-dependent synergy has been demonstrated in vitro between irinotecan and cisplatin. A phase I trial conducted at Memorial Sloan-Kettering Cancer Center (MSKCC) has demonstrated the safety and tolerability of cisplatin plus irinotecan. A phase II study of this combination in patients with previously untreated, advanced esophageal cancer, also at MSKCC, has demonstrated promising results. Current trials at MSKCC are attempting to combine this regimen with either paclitaxel (Taxol), fluorouracil (5-FU), or radiation therapy. PMID- 11200146 TI - Irinotecan in the management of patients with pancreatic cancer. AB - Synergy with no overlapping toxicities has been demonstrated for the combination of irinotecan (Camptosar, CPT-11) and gemcitabine (Gemzar) in vitro. Results of a single-institution phase I study in which patients with previously untreated pancreatic cancer were given irinotecan and gemcitabine were promising, with two of three patients achieving a partial response. Because of the favorable outcome of the phase I study, a multicenter phase II trial was undertaken in previously untreated patients with pancreatic carcinoma. Data from other sites entering patients in this phase II study have been analyzed, and a multicenter phase III trial of single-agent gemcitabine vs the irinotecan combination in first-line treatment of patients with locally advanced or metastatic pancreatic cancer is underway. PMID- 11200147 TI - Phase I study of irinotecan and concurrent radiation therapy for upper GI tumors. AB - Irinotecan (Camptosar) is an active chemotherapeutic agent for lung, gastric, esophageal, and colorectal cancers and a potent radiosensitizer. This phase I study was designed to assess the maximum tolerated dose of weekly irinotecan combined with concurrent radiotherapy for patients with locally advanced, unresectable gastric, gastroesophageal junction, or esophageal cancer. Patients who received previous chemotherapy (excluding irinotecan) or who experienced recurrent cancer after surgery were eligible for this protocol. The total dose of radiation did not exceed 50.4 Gy (28 fractions of 1.8 Gy each). The starting dose level of irinotecan was 30 mg/m2 infused over 90 minutes given weekly for 5 weeks. Subsequent dose levels were increased in 10 mg/m2 increments to 40, 50, 60, and 70 mg/m2. Of 15 patients who have been enrolled to date, all are evaluable for toxicities and 12 for response. Major hematologic toxicities (grade 3/4) were neutropenia, chills, hemorrhage, and anemia. Grade 3/4 gastrointestinal toxicities included nausea, vomiting, dehydration, anorexia, and constipation. Other severe nonhematologic toxicities included fatigue, hypotension, and hypothermia, as well as cardiovascular toxicities. There was no severe diarrhea and no treatment-related deaths. Of the 12 evaluable patients, 7 (58%) responded, including 2 complete responses; 4 (30%) had no change and 1 had progressive disease. Survival ranged from 1 month to 15 months, with a median survival of 8 months. When the total dose of irinotecan given concurrently with radiotherapy was higher than 250 mg/m2, patients experienced significantly more severe grade 3/4 toxicities than with lower doses (P = .04), with no improvement in response rate. It was concluded that weekly doses of irinotecan of up to 60 mg/m2 with concurrent radiotherapy given over 5 weeks was feasible and demonstrated good response. This regimen did not cause severe diarrhea or pneumonitis, but neutropenia and fatigue were major toxicities. The study continues to accrue. PMID- 11200148 TI - Colorectal cancer: chemotherapy treatment overview. AB - Fluorouracil (5-FU) has remained the standard therapy for the treatment of advanced colorectal cancer for over 40 years. Unfortunately, only a minority of patients experience objective clinical response. Discussed herein are attempts to improve on the activity of 5-FU by biochemically modulating its action. In addition, novel agents for the treatment of advanced colorectal cancer (oral fluoropyrimidines, oxaliplatin, and irinotecan) are discussed. Oral fluoropyrimidines (UFT plus leucovorin, capecitabine, eniluracil plus oral 5-FU) provide the convenience of oral delivery with a marked reduction in febrile neutropenia and mucositis. Recent randomized trials with these agents have demonstrated therapeutic activity that is comparable with intravenous schedules of 5-FU plus leucovorin. Compared to 5-FU, both oxaliplatin and irinotecan have uniquely different mechanisms of action and have demonstrated clinical activity in patients whose disease has progressed with 5-FU treatment. Combinations of either irinotecan or oxaliplatin plus 5-FU/leucovorin have demonstrated that the addition of these agents to 5-FU/leucovorin improves response rates and time to progression compared to 5-FU/leucovorin alone. Combination chemotherapy regimens with these novel agents are rapidly being introduced into the adjuvant setting. PMID- 11200149 TI - Irinotecan-based combinations for the adjuvant treatment of stage III colon cancer. AB - Irinotecan (Camptosar) is a topoisomerase I inhibitor with demonstrated antitumor activity against a wide variety of malignancies. Phase II studies have shown that this agent has significant single-agent activity against both chemotherapy-naive and fluorouracil (5-FU)-refractory colorectal cancer. Phase III studies now indicate that irinotecan/5-FU/leucovorin combinations have antitumor activity superior to standard 5-FU/leucovorin regimens alone. These irinotecan-based combinations are now entering clinical trials for the adjuvant treatment of resected stage III colon cancer. It is hypothesized that the superior antitumor activity of these irinotecan-based combinations seen in the metastatic setting will translate into improved survival and increased cure rates in these earlier stage patients. PMID- 11200150 TI - Irinotecan and high-dose fluorouracil/leucovorin for metastatic colorectal cancer. AB - Two randomized phase III trials with irinotecan as second-line treatment of metastatic colorectal cancer have shown that irinotecan (CPT-11, Camptosar) significantly improves survival when compared with best supportive care or continuous infusion of fluorouracil (5-FU) after failure of 5-FU. The combination of irinotecan and 5-FU/leucovorin produced a significantly higher response rate (40.8% vs 23.1%, P < .001), longer time to progression of disease (6.7 vs 4.4 months, P < .001), longer median survival (17.4 vs 14.1 months, P = .03), and a greater chance of survival at 1 year (69% vs 59%, P = .03) than 5-FU/leucovorin treatment alone. Such benefits have not previously been demonstrated in this setting. Although the use of irinotecan in combination with 5-FU/leucovorin increased the likelihood of neutropenia, the incidence of febrile neutropenia and infection remained low. Other toxic effects were manageable, noncumulative, and reversible. PMID- 11200151 TI - Irinotecan in preoperative combined-modality therapy for locally advanced rectal cancer. AB - Irinotecan (CPT-11, Camptosar) is a semisynthetic water-soluble derivative of the plant alkaloid camptothecin. This review will focus on the potential use of irinotecan in combination with fluorouracil (5-FU) in the preoperative combined modality treatment of advanced rectal cancer. The laboratory studies that define the mechanism of fluoropyrimidine- and camptothecin-mediated radiosensitization are discussed, and the rationale for combined-modality therapy using radiation with 5-FU and irinotecan is presented. PMID- 11200152 TI - Is there a need for plasticizer-free biomaterials in dialysis therapy? AB - The impact of plasticizers on general health is an extremely controversial subject. Most of the results in this area, especially those related to di ethylhexyl-phthalate, are collected from animal studies and the extrapolation to humans is still controversial and difficult. This review of research findings explores the science of using soft polyvinyl(chloride). With particular reference to dialysis, it explains why some companies now offer products made of plasticizer-free biomaterials. PMID- 11200153 TI - Microsystems: how to access the technology. AB - Microsystems are devices that incorporate a combination of microfluidic, micromechanical, micro-optical and microelectronic components. This users' guide provides information on how to access the technology and find the resources needed for design, prototyping and manufacture in Europe. PMID- 11200154 TI - Another design input: reimbursement issues. AB - In spite of diverse challenges, medical device companies are continuing to design and develop high quality products that significantly benefit patients. They are also succeeding in meeting increasingly stringent regulatory requirements. However, these accomplishments do not guarantee commercial success. The importance of designers considering the needs of purchasers during the design phase is examined. PMID- 11200155 TI - The medical device industry prepares to blow its own trumpet. PMID- 11200156 TI - Reuse of single-use devices. AB - The lack of regulation and procedures to monitor the reuse of single-use devices (SUDs) is allowing the use of medical devices that can pose a risk to patient health. Studies on reused SUDs show a range of defects. Despite this, uncontrolled reuse of SUDs continues. This article explores the extent of the problem, reports the findings of some of the studies and suggests what should be done. PMID- 11200157 TI - What the Internet means for the medical device industry. AB - The Internet is dramatically changing the structure of the industry. For the first time, direct communication between all suppliers and all hospitals is available. The Internet-based electronic market place not only provides the ability to choose products from a standardized catalogue, but also to send orders direct to suppliers' enterprise resource planning systems. One-to-one marketing is also becoming a reality. Medical device manufacturers are advised to test the different electronic sales and marketing initiatives that are now available. PMID- 11200158 TI - Japan. The high-tech giant. PMID- 11200159 TI - China. Huge long-term potential. PMID- 11200160 TI - Singapore. A favoured distribution centre. PMID- 11200161 TI - Thailand in recovery. PMID- 11200162 TI - South Korea. Fastest growing future. PMID- 11200163 TI - Taiwan. A great exporter. PMID- 11200164 TI - India. A flourishing private sector. PMID- 11200165 TI - Pakistan. In early development. PMID- 11200166 TI - Vietnam. Determined to renovate. PMID- 11200167 TI - The 2000 Medical Device Technology employment survey. PMID- 11200168 TI - Home-care products. PMID- 11200169 TI - PVC and medical devices: making an informed choice. PMID- 11200170 TI - NMDA receptors and nitric oxide regulate prostaglandin D2 synthesis in the rabbit hippocampus in vivo. AB - The aim of this in vivo microdialysis study was to characterise the regulation of prostaglandin D2 (PgD2) synthesis by NMDA receptors in the rabbit hippocampus in relation to changes in extracellular Ca2+ concentration ([Ca2+]e) and nitric oxide (NO) levels. Samples of dialysate were analysed for changes in PgD2 concentration, in [Ca2+]e and in the level of NO. The results demonstrated that a 20-min pulse application of 0.1-2.5 mM NMDA via a microdialysis probe induced a prolonged stimulation of PgD2 release that was sensitive to competitive NMDA receptor antagonists. An inhibitor of voltage-sensitive Na+ channels, tetrodotoxin, did not influence this effect but significantly suppressed basal PgD2 production, whereas a NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L NAME), prevented NMDA-evoked NO release and inhibited NMDA-induced PgD2 release in an L-arginine-sensitive manner. NO donors, S-nitroso-N-acetylpenicillamine and sodium nitroprusside, stimulated PgD2 release. NMDA-evoked decrease in [Ca2+]e was insensitive to TTX and L-NAME. These results demonstrate an in vivo NMDA receptor-mediated modulation of PgD2 synthesis in the brain, in which NO participates. PMID- 11200171 TI - Postmicrosomal protein fractions from short-time-predegenerated rat sciatic nerve. AB - The postmicrosomal protein fraction obtained from distal stumps of rat sciatic nerves at 0-6 days following transection were investigated by means of one- and two-dimensional electrophoresis. In all experimental groups, total amount of protein was significantly higher than in the control group. Proteins were resolved into 27 bands after SDS-PAGE. Their molecular weights ranged between 16.2 and 335.4 kDa. Eleven fractions displayed significant quantitative differences. After 2-D-electrophoresis, the pI of the proteins ranged from 4.2 to 7.4. They were resolved to 28 molecular masses from 13.5 kDa to 335.4 kDa. The greatest numbers of fractions (90-109) were observed on the 3rd, 4th, 5th and 6th day after nerve transection. Thus, during first 6 days after transection intensive changes in protein fraction content and composition take place in the distal stump of peripheral nerve. These processes seem to be most prominent on the 4th day after lesion. Results confirm our earlier in vivo findings. PMID- 11200172 TI - Effects of acute and chronic triazolam treatments on brain GABA levels in albino rats. AB - The present study investigated the effects of acute and chronic intraperitoneal administration of Triazolam on g-aminobutyric acid (GABA) levels in different brain areas of albino rats. Three experiments were conducted. In the first, five groups of rats were acutely treated with different doses of Triazolam (0.25 mg/kg 4.0 mg/kg). In the second experiment, rats were treated chronically with a single daily dose of Triazolam (started with 0.25 mg/kg and increased by time to 1.0 mg/kg) for 5 weeks, simulating clinical use. In the third, rats were treated chronically with three daily doses of Triazolam (started with 0.25 mg/kg and increased by time to 0.5 mg/kg) for 20 days, representing a form of drug abuse. Brain levels of GABA and plasma levels of Triazolam were measured using high performance liquid chromatography (HPLC). The acute Triazolam administration produced an increase in GABA levels in all brain areas studied. The chronic administration of single daily dose of Triazolam produced normal GABA levels in all brain areas except brain stem where the levels were significantly decreased; this indicates the development of tolerance to Triazolam action on increasing GABA content. The chronic administration of three daily doses of Triazolam produced a decrease in GABA levels in all brain regions studied. In conclusion, chronic single daily dose treatment (representing normal use) produces tolerance to Triazolam effects on brain GABA levels, while chronic three daily doses administration (akin to drug abuse) causes a fall in GABA levels. PMID- 11200174 TI - Expectation of an important event affects responses to irrelevant stimuli of different modalities. AB - Periodic alterations of event-related potentials (ERPs) were studied during "oddball" tasks. Sequences of randomly intermixed frequent (non-target) and rare (target) stimuli were presented. In visual experiments, these were flashes of light of two different colors. In auditory tests there were two tones of different frequencies. The instruction was to keep a mental count of each target stimulus. To study the alterations of the "state of the brain" produced by target detection, responses to non-targets immediately following targets were compared with responses to an eighth subsequent non-target stimulus. To evaluate the effect of such "brain states" on responses to stimuli of a different modality, additional visual stimuli (probes) were delivered after both auditory and visual "oddball" stimuli. It was found that responses to the eighth presentation of non target stimulus were preceded by significant negative shift of recorded potential. This shift was smaller before the responses to non-targets immediately following the presentation of target stimuli. The difference was significant both in auditory and visual tests. Responses to "oddball" stimuli were little affected: only the reduction of P200 peaks in "after target" responses was significant in visual tests. Responses to probes showed stronger effects: when visual probes followed visual "oddball" stimuli, all three components measured (N100, P130 and P200) were shifted positively in responses to eighth presentations of non-targets. When visual probes were presented in auditory tests, only the amplitude of the N100 component was significantly affected. PMID- 11200173 TI - Escape from shock versus escape from shock accompanied by a visual stimulus in rats. AB - Two groups of 15 rats each were trained in a shuttle box to escape foot-shock either unsignalled or presented in compound with a visual cue: darkness. The visual cue presented in shock compartment amplifies the behavioral tendency actually prevailing in the response repertory of the rat. During the 1st session the compound enhanced the species-specific flight resulting in shortening of the rat's escape latency. Thereafter, during subsequent sessions, darkness exaggerated resistance to enter the other compartment; thus escape latencies were longer under compounded than under unsignalled procedure. The darkness cue reduces the intertrial response rate relative to the unsignalled group. This latter finding supports the discrimination model of the effect, since the compound helps the animals to discriminate the illuminated "safe" period between trials from the aversive shock period. Our data seem to suggest that the darkness presented synchronously with escapable grid-shock acquires aversive properties. PMID- 11200175 TI - Spontaneous behavior of the gray short-tailed opossum (Monodelphis domestica) in the elevated plus-maze: comparison with Long-Evans rats. AB - We observed the spontaneous behavior of a laboratory marsupial--the gray short tailed opossum (Monodelphis domestica)--in the elevated plus-maze (EPM) during six consecutive sessions and compared it with the behavior of Long-Evans rats. During the first exposure to the maze both species spent most of the time in the enclosed arms but opossums showed much higher frequency of entries into the open arms and stayed there longer. On the third and subsequent days opossums reduced their entries into the open arms and spent more time on the central square, where unlike rats they frequently groomed their lower belly and hind legs. During the last sessions they started spending more time in the enclosed arms. It is concluded that probably opossums, like rats show a stable anxiety evoked by open space. However, in the rat anxiety prevails over motivation to explore a new environment, while in the opossum it is initially at equilibrium with curiosity which habituates slower than in the rat. Results are discussed in the context of different ecology of the gray opossum that actively searches and hunts quickly moving insects. Thigmotaxic behavior, while strong in both species, dominates spontaneous behavior of the rat, but not opossum. PMID- 11200176 TI - Effect of unilateral injection of MK-801 into the area of A10 cells on feeding evoked by stimulation of homologous area in the contralateral hemisphere. AB - It was found previously that unilateral electrolytic and 6-OHDA lesions of the ventral tegmental area (VTA) and unilateral intra-VTA injection of bicuculline resulted in facilitation of behavioral responses evoked by electrical stimulation of the symmetrical VTA area in the contralateral hemisphere. We postulated that "the contralateral facilitation effect", which may reflect the yet unexplored mechanism of immediate compensation after acute unilateral brain injury, is attributable to the A10 DA neurons and their regulatory inputs. The present study was aimed at examining the possible involvement of NMDA-mediated glutamatergic transmission in VTA in the "contralateral facilitation effect". The behavioral model of the VTA stimulation-induced feeding in rats was used. Latency to eat was measured as a function of stimulation frequency before and after unilateral intra VTA injection of non-competitive NMDA receptors antagonist, MK-801, (doses 0.0, 1.25 and 2.5 micrograms). MK-801 caused a dose-dependent augmentation of feeding evoked by stimulation of the contralateral VTA, which manifested as a decrease in the reaction frequency threshold and a leftward shift of the latency/frequency curve. Dose 2.5 micrograms replicated the facilitatory effect of electrolytic and 6-OHDA lesions. The results are interpreted in terms of MK-801-evoked depression of excitatory glutamatergic tone over A10 DA cells and compensatory increase in DA release in the contralateral hemisphere. PMID- 11200177 TI - Complexity analysis of spontaneous EEG. AB - The aim of the present paper is the assessment of the overall complexity of spontaneous and non-paroxysmal EEG signals obtained from three groups of human subjects, e.g., healthy, seizure and mania. Linear complexity measure suitable for multi-variate signals, along with nonlinear measures such as approximate entropy (ApEn) and Taken's estimator are considered. The degree of linear complexity is significantly reduced for the pathological groups compared with healthy group. The nonlinear measures of complexity are significantly decreased in the seizure group for most of the electrodes, whereas a distinct discrimination between the maniac and healthy groups based on these nonlinear measures is not evident. PMID- 11200178 TI - Phonological and semantic fluencies are mediated by different regions of the prefrontal cortex. AB - Verbal phonological and semantic fluencies were investigated in 24 patients with unilateral prefrontal lesions and 10 normal control subjects. Lesions were limited to small areas within either the dorsolateral (Brodmann's area 46/9) or ventromedial (posterior part of the gyrus rectus) cortices. In a phonological fluency task, patients with lesions to the left dorsolateral region were impaired. In semantic fluency, not only the left dorsolateral group but also the two right frontal damaged groups performed worse than the control group. In agreement with previous studies, our results show that the phonological fluency is mediated by the left dorsolateral prefrontal cortex. In contrast to this, performance on the semantic fluency task depends on a wider portion of the prefrontal cortex involving the left and right dorsolateral and the right ventromedial areas. PMID- 11200179 TI - Protein kinase C in the barrel cortex. PMID- 11200180 TI - Acute Ginkgo biloba facilitates decision-making in a working memory task in rats. PMID- 11200181 TI - Brain injury: prolonged induction of transcription factors. AB - A specific temporal order of events at the cellular and molecular level occurs in response to injury to the brain. Injury-compromised neurons degenerate while surviving neurons undergo neuritogenesis and synaptogenesis to establish neuronal connectivity destroyed in the injury. Several genes, such as those coding cytoskeletal proteins and growth factors, have been shown to be regulated by AP-1 and NF-kappa B transcription factors, two of the most studied DNA binding regulatory proteins. Our laboratory has discovered that Fos-related antigen-2 from AP-1 transcription factor family and NF-kappa B p65 and p50 subunits are induced long-term (days to months) in the brain after neurotoxic, excitotoxic or ischemic insult. Fos-related antigen-2 is induced in neurons in several models of injury and its elevated expression lasts days to months, corresponding to the severity. The time-course of FRA-2 induction is abbreviated with less severe insult (terminal damage) relative to the cell death, but the induction occurs during the period of regeneration and repair in both models. NF-kappa B p65 is basally expressed in hippocampal and cortical neurons, but is elevated in reactive astrocytes in hippocampus and entorhinal cortex starting at two days and lasting at least two weeks after kainate treatment. Neurons of the hippocampus surviving ischemic or neurotoxic injury increase expression of NF-kappa B p50 for at least a week after injury, suggesting a function for p50 in neuronal survival and/or repair. The extended expression of these transcription factors implies a role in the activation of genes related to repair and regeneration, such as growth factors and synaptic proteins, after injury to the CNS. PMID- 11200182 TI - Signaling pathways mediating anti-apoptotic action of neurotrophins. AB - Neurotrophins promote survival and suppress apoptosis in many populations of neurons. Currently, phosphatidylinositol-3 kinase (PI-3K) is recognized as the main mediator of this protective effect. However, most of the data collected so far on the anti-apoptotic signaling of neurotrophins were obtained using trophic withdrawal paradigms. Recent data from our and other groups indicate that extracellular-signal-regulated kinase 1/2 (Erk 1/2) may play a critical role in suppressing neuronal apoptosis triggered by cellular damage. Thus, it appears that either Erk1/2 or PI-3K, depending on the nature of the death-inducing stimulus, can mediate anti-apoptotic signaling of neurotrophins. In this review, we discuss the contribution of Erk1/2 and PI-3K to neuroprotection by neurotrophins. We also present data suggesting possible mechanisms by which these pathways might suppress neuronal death. PMID- 11200183 TI - ITF mapping after drugs of abuse: pharmacological versus perceptional effects. AB - Analysis of inducible transcription factors (ITFs) expression is often applied to map drug-induced changes of neuronal activity in brain. Administration of cocaine and alcohol induces ITFs in a large number of brain structures. However, induction of ITFs in a brain region does not necessarily indicate a pharmacological effect of the drug in this brain region. Many of the brain regions could be activated by secondary effects. Perception of stimulus properties of the drug or locomotor effects of the drug are possible secondary effects. Anesthesia can block induction of ITFs by cocaine and alcohol suggesting that ITF expression in a majority of brain regions is more sensitive to secondary effects than to pharmacological effects of these drugs. In agreement with this hypothesis is our finding that the majority of brain regions responding with ITF expression to alcohol administration do not respond to voluntary alcohol self administration in animals. Only a few brain regions show similar ITF induction after both administration and self-administration of this drug. Presumably these brain regions could be responding to pharmacological effects of alcohol. Given the low resolution of invasive techniques, ITF mapping experiments will continually contribute to our understanding of mechanisms of drug addiction and alcoholism. PMID- 11200184 TI - Effect of opioids on Ca2+/cAMP responsive element binding protein. AB - Ca2+/cAMP response element binding protein (CREB) is an important factor linking the opioid-regulated secondary messenger systems to alterations in gene expression. Opioids regulate CREB level, its phosphorylation and binding to its corresponding response element in the promoters of several genes implicated in drug addiction. CREB mediates the action of opioids on the expression of several genes in brain regions responsible for drug-seeking behavior and manifestation of signs of dependence. Moreover, alterations in CREB level can effect the rewarding properties of morphine and regulate the self-administration of cocaine. At the cellular level CREB acts as convergence point for different cellular pathways. Opioids affect two different intracellular mediator systems: inhibitory- connected with cAMP, and stimulatory--involving calcium and the PKC pathway. Both can affect CREB but in different phases of opiate action. The presence of this biphasic mechanism can explain the phenomenon of the induction of some CRE controlled genes after both acute and chronic morphine administration. Cellular studies also highlight the relevance of other ATF/CREB family members which can affect Ca2+/cAMP response element (CRE) controlled transcription as well as other transcription factors which make the opioid induction longer lasting. PMID- 11200185 TI - Regulation of cell specific expression of calcyclin (S100A6) in nerve cells and other tissues. AB - Many of the small, acidic, calcium binding S100 proteins present in the brain specifically map different anatomical regions and cell types and their overexpression is implicated in pathological changes. Similarly to other members of the S100 protein family, calcyclin (S100A6) is expressed in a cell specific manner and is found in subpopulations of neurons and astrocytes in the brain and in epithelial cells and fibroblasts. In this article we review data concerning the cell specific expression of S100 protein genes and present experimental results on the regulation of the calcyclin gene. We have performed promoter deletion studies to locate regions within the calcyclin gene promoter responsible for transcriptional regulation. The results demonstrate that the 3 kb long calcyclin gene promoter lacks a cell specific cis-acting element and drives the expression of the reporter gene also in cells that do not express endogenous calcyclin. The expression is modulated by positive and negative elements acting uniformly in the four different cell lines studied. The first intron of the calcyclin gene was found to have an inhibitory influence on expression regardless of cell type. It was also shown that calcyclin expression can be induced in calcyclin-negative cells by treatment with 5-azacytidine suggesting the involvement of gene methylation in its cell specific expression. The results are discussed in light of the data available on the regulation of other S100 genes. PMID- 11200186 TI - A new CAPD battery--multiple auditory processing assessment: factor analysis and comparisons with SCAN. AB - Based on recommendations by Musiek & Chermak (1994, American Journal of Audiology, 3, 23-27) and ASHA (1996, American Journal of Audiology, 5(2), 41-54), a battery of four commonly used tests was selected and recorded for use in assessing school children. These tests were labeled the Multiple Auditory Processing Assessment (MAPA) and then administered to an initial sample of 81 third grade children, along with the SCAN screening test for auditory processing disorders. Afterward, several exploratory factor analyses were performed on the findings, and comparisons were made between the results for the MAPA and SCAN. Four separate factors emerged from the four MAPA tests, which were linked closely to the components of central auditory processing disorders (CAPDs) defined by ASHA (1996, American Journal of Audiology, 5(2), 41-54). These factors were labeled monaural separation/closure (MSC), auditory pattern/temporal ordering, binaural integration, and binaural separation (BS). SCAN appears to measure two of these factors, MSC and BS. Use of MAPA is encouraging. Our findings suggest it may provide an appropriate multiple-test, CAPD battery for third grade children, and it meets at least some of the objectives described in the consensus document proposed by ASHA (1996, American Journal of Audiology, 5(2), 41-54). PMID- 11200187 TI - A holistic model for matching high-tech hearing aid features to elderly patients. AB - Successful hearing aid fittings using high-technology features for elderly patients require consideration of factors beyond results obtained from routine audiologic evaluations. A holistic hearing aid selection, fitting, and evaluation approach that considers patient characteristics from communication, physical, psychological, and social assessment domains is presented here along with a checklist and flowcharts for matching high-tech hearing aid features to older persons who are hearing aid candidates. PMID- 11200188 TI - Behavioral auditory assessment of young infants: methodological limitations or natural lack of auditory responsiveness? AB - The determination of auditory thresholds by means of behavioral techniques in young infants can be difficult. This could be the result of limitations in methodology, a lack of observable auditory responsiveness, or both. In the current study, 2- and 4-month old infants were tested under enhanced conditions for obtaining behavioral responses (i.e., salient auditory stimuli, reduced visual distractions, reinforced correct responses). A two-interval, forced-choice task with four intensity levels was used. Although a behavioral threshold was obtained for the 4-month-olds, threshold determination for the 2-month-olds remained elusive. In light of the current findings and previous studies of visual acuity of infants, these results suggest a lack of behavioral responsiveness to auditory stimuli for the younger infants rather than methodological limitations. With infants in the 2-month-old age range, clinical audiologists should expect few behavioral responses to auditory stimuli at intensity levels below those that elicit startle responses. PMID- 11200189 TI - Insert earphone depth and the occlusion effect. AB - Twenty individuals were tested to determine the occlusion effect caused by supraaural earphones and by insert earphones with shallow and deep insertion of its foam eartip. The bone-conduction oscillator was placed both on the forehead and the mastoid. It was concluded that using deeply inserted earphones is the most practical way in which to carry out clinical bone-conduction measurements. PMID- 11200190 TI - An investigation of maternal stress after neonatal hearing screening. AB - An investigation was undertaken to determine whether mothers whose infants failed a newborn hearing screening (MWIF) had significantly more stress and were consequently at risk for dysfunctional attachment than those mothers whose infants passed a newborn hearing screening (MWIP). The Parenting Stress Index (PSI; Abidin, 1995), a screening and diagnostic assessment questionnaire designed to measure the relative magnitude of stress in a parent-child dyad, was used. Twenty MWIP and 20 MWIF participated. The PSI was administered through a telephone interview approximately 1 month after participants' discharge while their infants were between their fourth and fifth week of life. In the case of MWIF, the interview occurred before their infant's hearing retest. No significant differences in Total Stress, Life Stress, Child Domain, and Parent Domain subscale raw scores of the PSI were found between MWIP and MWIF (p > .05). An examination of the individual PSI profiles of all participants for "high" and "low" normative percentile scores (i.e., percentile scores > or = 90th percentile and percentile scores < or = 0 percentile for the former and latter, respectively) revealed that the incidence of high scale/subscale percentile scores was essentially equivalent between groups. MWIP, however, displayed lower scale/subscale percentile scores. The results of the study suggest that those mothers whose infants receive a refer outcome after a newborn hearing screening demonstrate equivalent stress levels as those mothers whose infants received a pass. PMID- 11200191 TI - Outcome of newborn hearing screening by ABR compared with four different DPOAE pass criteria. AB - The purpose of this study is to compare the effectiveness and utility of distortion product otoacoustic emission (DPOAE) and auditory brain stem response (ABR) testing as screening methodologies suitable for universal application at a large birthing hospital. Five hundred sixty-nine neonates (1184 ears) without risk indicators for hearing loss underwent DPOAE and ABR screening before hospital discharge at birth. All ears (100%) passed the ABR screening. DPOAE results were categorized on the basis of the number of frequencies at which emissions were obtained as well as presence versus absence of a replicated response at each test frequency. Pass and refer rates varied widely, on the basis of whether the presence of DPOAE response at 2000 Hz or replication were required. With the most stringent criteria, only 64.44% of ears passed, whereas with the least stringent criteria 88.94% passed. Given that 100% of ears passed according to the gold standard of the ABR screening, these results indicate false positive rates ranging from 11% to 35% by DPOAE screening. This discrepancy in pass and refer rates when various criteria are applied indicates the need for standardization and further comparison of appropriate pass criteria for newborn hearing screening programs. PMID- 11200192 TI - Speech and language screening for audiologists. AB - Speech and language screening by audiologists is not new, although few audiologists screen speech and language, which should be an integral component of the audiological evaluation. This article considers ASHA's views about speech and language screening by audiologists, screening tests available to audiologists, and the training of audiologists to screen speech and language. PMID- 11200193 TI - Central auditory processes and test measures: ASHA 1996 revisited. AB - The theoretical issues surrounding central auditory processing disorders (CAPD) are reviewed here, especially with reference to the central auditory behavioral processes and the auditory test measures as prescribed in the ASHA (1996, American Journal of Audiology, 5(2), 41-54) statement on CAPD. A simplified nomenclature is recommended that directly relates process and test measure to facilitate the diagnostic process in CAPD. This new terminology closely follows the ASHA (1996, American Journal of Audiology, 5(2), 41-54) document, but provides some refinement based on recent research in CAPD. To support this recommendation, a confirmatory factor analysis (CFA) was applied to the findings of Domitz and Schow (2000, American Journal of Audiology), who proposed use of a battery of CAPD tests, the Multiple Auditory Processing Assessment (MAPA) for testing school children. The CFA was found to reinforce the four-factor model, which clearly emerged in the exploratory factor analysis of Domitz and Schow. The model was found to be reasonably consistent even when subtests from the SCAN were included in the analysis. Refinement and revision of ASHA (1996, American Journal of Audiology, 5(2), 41-54) is recommended to facilitate diagnosis, subclassification, and intervention for CAPD. PMID- 11200194 TI - Celebrating a decade of evaluation and treatment: the University of Maryland Tinnitus & Hyperacusis Center. AB - The University of Maryland Tinnitus & Hyperacusis Center in Baltimore was the first center in the United States dedicated to the evaluation and treatment of tinnitus and hyperacusis patients implementing an habituation-based protocol that has become known internationally as Tinnitus Retraining Therapy (TRT). A crucial feature of the model is the postulate that a number of systems in the brain are involved in the emergence of tinnitus. The cochlea and auditory periphery play only a secondary role. To facilitate the goal of habituation of the tinnitus signal, TRT implements both directive counseling to neutralize the negative emotional associations toward the tinnitus, and sound therapy to interfere with the signal. As an outgrowth of the work with tinnitus, the evaluation and treatment of hyperacusis has emerged as an increasingly important part of our program. This report describes the unique facility, staff, and services of the Center as we celebrate a decade of research and clinical management dedicated to the scientific understanding of tinnitus and hyperacusis. PMID- 11200196 TI - List equivalency and test-retest reliability of the Speech in Noise test. AB - The Speech in Noise (SIN) test consists of a series of Institute of Electrical and Electronic Engineers sentences presented in a background of four-talker babble at two presentation levels (83 and 53 dB SPL) and four signal-to-noise ratios (SNR) (15, 10, 5, and 0 dB). In this study, the nine lists were tested for equivalency and the test-retest reliability was determined. Twenty listeners with normal hearing and 20 listeners with sloping sensorineural hearing losses served as subjects. Five sentences were presented at each SNR at each level, and five key words in each sentence were scored (100 key words per presentation level). Each key word was scored as correct or incorrect, with errors of plurality scored as half-correct words. For percent-correct scores, Lists 1, 2, and 9 and Lists 3, 4, and 5 were found to be equivalent for listeners with normal hearing. For both groups of listeners, the test-retest correlations were high, and the critical differences appropriate for sentence material were 10 to 16% at a .95 level of confidence. Because of floor and ceiling effects across the different lists, many subjects with normal hearing did not score as low as the 50% level, and many subjects with hearing loss did not score as high as 50%. Suggestions are offered for alternate scoring in order to obtain a SNR for 50% performance. Future versions of this test should be designed with improved list equivalency and 50% performance capability. PMID- 11200195 TI - Outcomes analysis for hearing conservation programs. AB - In health care, an increasing interest in accountability for outcomes, proof of quality care, and cost effectiveness is forcing many practitioners, including audiologists, in the direction of using outcomes analysis to provide proof of performance in their practices. Critical to the conduct of outcomes analysis are the selection of valid outcomes metrics and application of appropriate statistical processes. Modeling of clinical protocols is a useful exercise for developing outcomes data and data management standards. The authors describe the implications for wider use of outcomes modeling once the Health Insurance Portability and Accountability Act (HIPAA) administrative simplification law is implemented. This legislation will set up a wholly new administrative data set that has strong potential to provide outcomes metrics to a variety of Audiology practices. The modeling exercise described here was originally intended to derive assessment outcomes for evaluating hearing conservation program effectiveness in military populations from an administrative database implemented within the Military Health System starting in 1997. The outcomes modelers, however, soon realized the broader applicability of modeling techniques for other special populations and Audiology practices, particularly with the oncoming startup of HIPAA legislative mandates. The modeling exercise demonstrates a process of structuring standard health-care codes to produce outcomes data for epidemiologic and cost analyses, thereby providing better information to guide health-care practices toward improving quality and cost effectiveness. This information in time series should also provide a record of continuous quality improvement. The authors present a general hearing surveillance protocol for evaluating occupational hearing loss. The protocol is used as a specific instance to demonstrate the shaping of an outcomes metrics model. This same process can be applied more generally when used to model outcomes data from other audiology practices. Implementation of the administrative data model described here began at more than 400 Department of Defense (DOD) medical treatment facilities worldwide as of October 1, 1999. The exercise of developing similar outcomes metrics for newborn hearing screening programs, school hearing conservation programs, and other clinical and rehabilitative audiology practices in the civilian sector remains to be done. PMID- 11200197 TI - Social work practice and the Internet: Part 2--Online discharge planning and telemedicine. PMID- 11200198 TI - Preparing for a JCAHO survey: Part 6. PMID- 11200199 TI - Raising the bar: improving standards for social work practice in long-term care- Part 2. PMID- 11200200 TI - Social work home visits: impact on recidivism and health care costs. PMID- 11200201 TI - Climate change and stratospheric ozone depletion. Early effects on our health in Europe. PMID- 11200202 TI - Importance of positioning and technical factors in anatomic localization of sporting injuries in scintigraphic imaging. AB - Sports medicine is becoming increasingly important as more people take up exercise for health and well-being. It is adding to the spectrum of acute and chronic injuries that have traditionally been seen in elite or professional athletes. Because of its high sensitivity and lesion contrast, bone scintigraphy has traditionally played a key role in the detection of such injuries. This role has been reduced in recent times by the increased use of magnetic resonance imaging (MRI), which has functional capability, high-contrast resolution, and high-spatial resolution. Bone scintigraphy has the capability of detecting early cortical ligament avulsion and enthesopathic disease before the onset of edema or changes in bone marrow that are detected by MRI. If this capability is added to more precise anatomic localization of lesions, we may see a resurgence in its use in sports medicine. A number of techniques are presented in this article, encompassing positioning, special views, and tomographic reconstructions, that can significantly improve the accuracy of localization of scintigraphic abnormalities with reference to anatomic models or sources of cross-sectional anatomy. PMID- 11200203 TI - Quantitative studies of bone with the use of 18F-fluoride and 99mTc-methylene diphosphonate. AB - This article discusses methods for quantifying bone turnover based on tracer kinetic studies of the short-lived radiopharmaceuticals 99mTc-MDP and 18F fluoride. Measurements of skeletal clearance obtained by using these tracers reflect the combined effects of skeletal blood flow and osteoblastic activity. The pharmacokinetics of each tracer is described, together with some of the quantitative tests of skeletal function that have been described in the literature. The physiologic interpretation of quantitative measurements of bone obtained with the use of short half-life radionuclides is discussed, and the advantages and limitations of 99mTc-MDP and 18F-fluoride are compared and contrasted. Currently, 18F-fluoride dynamic positron emission tomography (PET) is the technique of choice for physiologically precise quantitative studies of bone. However, comparable data could probably be obtained by using 99mTc-MDP if methods for single photon emission computed tomography (SPECT) quantitation were improved. PMID- 11200204 TI - The role of single photon emission computed tomography in bone imaging. AB - Single photon emission computed tomography (SPECT) of the bone is the second most frequently performed SPECT examination in routine nuclear medicine practice, with cardiac SPECT being the most frequent. Compared with planar scintigraphy, SPECT increases image contrast and improves lesion detection and localization. Studies have documented the unique diagnostic information provided by SPECT, particularly for avascular necrosis of the femoral head, in patients with back pain, for the differential diagnosis between malignant and benign spinal lesions, in the detection of metastatic cancer in the spine, for the diagnosis of temporomandibular joint internal derangement, and for the evaluation of acute and chronic knee pain. Although less rigorously documented, SPECT is being increasingly used in all types of situations that demand more precise anatomic localization of abnormal tracer uptake. The effectiveness of bone SPECT increases with the selection of the proper collimator, which allows one to acquire adequate counts and minimize the patient-to-detector distance. Low-energy, ultrahigh resolution or high-resolution collimation is preferred over all-purpose collimators. Multihead gamma cameras can increase the counts obtained or shorten acquisition time, making SPECT acquisitions more practical in busy departments and also increasing image quality compared with single-head cameras. Iterative reconstruction, with the use of ordered subsets estimation maximization, provides better quality images than classical filtered back projection algorithms. Three dimensional image analysis often aids lesion localization. PMID- 11200205 TI - The role of positron emission tomography in skeletal disease. AB - The role of positron emission tomography (PET) in the evaluation and management of skeletal disorders is increasing. A number of reports are available in both benign and malignant disease with a variety of tracers. The bone agent 18F fluoride can be used to evaluate bone metastases both qualitatively and, for a number of focal and systemic skeletal disorders, quantitatively. 18 Fluorodeoxyglucose is used as a tumor agent in both primary and metastatic bone and bone marrow malignancies; its use has also been described in the evaluation of infection within the skeleton. A possible role for the use of the hypoxia selective tracer 18F-fluoromisonidazole in skeletal infection also exists. This article summarizes the current role of PET in the skeleton with regard to these tracers and diseases. PMID- 11200206 TI - The palliative management of skeletal metastases in prostate cancer: use of bone seeking radionuclides and bisphosphonates. AB - In prostate cancer, the development of skeletal metastases is associated with a significant increase in morbidity, mainly because of severe bone pain, which eventually becomes refractory to conventional analgesia. Androgen ablation is the treatment of choice, but the majority of patients relapse within 2 to 3 years from initiation of treatment. After failure of hormone therapy, external-beam irradiation therapy is effective in the palliation of pain, but radionuclides represent an attractive and cost-effective alternative. Strontium 89 is currently the most commonly used radionuclide in the palliative management of prostate cancer metastatic to the skeleton. The rationale for the use of bisphosphonates in metastatic prostate cancer is not immediately obvious, given the predominantly osteoblastic nature of the metastatic process. The clinical use of these agents rests on a number of basic and clinical observations that provide ample evidence that, in prostate cancer, the metastatic process is associated with increased bone resorption. Evidence regarding the beneficial effects of bisphosphonates in reducing morbidity from metastatic prostate cancer is reasonably solid, although the choice of optimal bisphosphonate, mode of administration, dose, and duration of treatment must be determined in large, controlled studies before their widespread clinical use can be advocated. Available therapeutic modalities that use either radionuclides or bisphosphonates can effectively and safely be used in the palliative management of metastatic prostate cancer. Neither radionuclides nor bisphosphonates have been shown to prolong survival, but the potential of both agents to beneficially alter the metastatic process in prostate cancer is intriguing. PMID- 11200207 TI - Bone densitometry and the diagnosis of osteoporosis. AB - Over the past decade, bone density scanning has come to be seen as an essential part of the evaluation of patients at risk of osteoporosis. Although dual x-ray absorptiometry (DXA) is the technique most associated with the recent growth in bone densitometry, several innovative devices for performing measurements at sites in the peripheral skeleton are also available. This article examines the question of whether there is any one method or measurement site that performs better than all the others at identifying patients at risk of fracture. Given that it is essential to make greater use of the small, low-cost peripheral devices if the many millions of women most at risk are to be identified and treated, what approaches to the interpretation of bone density scans can be adopted to ensure the greatest degree of consistency among different methods? Finally, does it matter if the imperfect correlation among different types of measurement results in different patients being selected for treatment on the basis of different techniques? PMID- 11200208 TI - Cold vertebrae on bone scintigraphy. PMID- 11200209 TI - False-positive uptake of 18F-fluorodeoxyglucose in the hilar region and mediastinum. PMID- 11200210 TI - Community-based health practices and their challenges in the future. PMID- 11200211 TI - Knowledge and perception of oral health promotion in schools among dental nurses in Sarawak, Malaysia. AB - In recent years, the concept of a Health-Promoting School has received much interest. In Malaysia, dental nurses are ideally placed to play a lead role in promoting Oral Health within the school setting. This study aims to provide information on the knowledge, perception and perceived role of Oral Health Promotion in schools, among dental nurses. A postal questionnaire was used to measure dental nurses' knowledge, perception and perceived role of Oral Health Promotion. The majority (60%) of dental nurses had good knowledge of Oral Health Promotion. Generally, they perceived that they play an important role in promoting Oral Health in schools. However, a sizeable proportion (25%) did not think they had a role to play in working together with school authorities to provide children with healthy food choices in school canteens. The majority (60%) of dental nurses did not perceive Oral Health Promotion to be important as a whole. They had a good perception of the concepts: it supports behaviour change, it has appropriate goals, it integrates oral health and general health and relieves anxiety. However, they had a poorer perception of the concepts; diverse educational approaches, participation, focus on prevention, early intervention, "spread of effect" of dental health education and "make healthier choices the easier choices". Years of service was not significantly associated with knowledge and perception of Oral Health Promotion. Dental nurses should be reoriented towards a more holistic practice of Oral Health Promotion. Workshops that invite active participation from dental nurses should be conducted to equip them with the necessary knowledge and skills. PMID- 11200212 TI - Knowledge, attitude and practice of smoking among university students of allied health sciences in Japan. AB - A study was conducted to determine the knowledge, attitude and practice (KAP) of cigarette smoking among freshman students of Tokyo Metropolitan University of Health Sciences. Students were categorized as 'ever-smoker' or 'nonsmoker'. 18.3% of the 356 subjects were categorized as 'ever-smoker'. The two categories were then compared to determine significant differences in health knowledge, attitudes towards health and smoking, smoking perceptions and preferences, knowledge on the economic impact of tobacco and attitudes towards tobacco control measures. In most cases, significant differences were found between the two groups. However, concerning knowledge on the economic impact of tobacco, the majority of both ever smokers and nonsmokers had poor knowledge. Increased tobacco control education and related efforts are needed as is further research in determining the factors or influences that shape the significant differences found. Such information will be invaluable in formulating appropriate tobacco control measures for the future. PMID- 11200213 TI - A comparative study of rural clinics in remote islands and inland areas. AB - The social and professional isolation of physicians remains an important issue in rural areas. However, few studies have investigated the involvement of geographic factors in the isolation. This study investigates rural public clinics in inland and remote island locations and attempts to objectively compare the isolation of these physicians. A mailed questionnaire was sent to rural clinics where graduate physicians from Jichi Medical School were working in 1994 and 1995. Among the 198 clinics with one or more full-time physicians, 185 (93 percent) responded to the inquiry. Geographic and demographic factors of the communities were compared between 43 clinics located in remote islands and the other 142 rural inland clinics. Rural clinics in remote islands have smaller subject populations, fewer part-time physicians, a longer journey to the nearest city, and a longer distance and travel time to the base hospital than rural inland clinics. Physicians in remote island clinics had less medical training and are more isolated than other physicians. More than half of the clinic physicians in remote islands have no regular training schedule, in contrast to less than a quarter of the inland clinic physicians. Almost all clinics (97.7%) in remote islands do not have a part-time physician, whereas about 20 percent of the rural inland clinics do. Physicians in remote island clinics are more socially and professionally isolated than those in inland clinics. Strategies to reduce these problems should be given priority in rural health policy and measures tailored to rural clinics in remote islands. PMID- 11200214 TI - Estimation of salt intake and recommendation for iodine content in iodized salt in Mongolia. AB - In 1996, the Mongolian Government pledged to eliminate iodine deficiency disorders by 2001 using salt iodization as its primary strategy. Iodine content in salt was set at 50 +/- 10 PPM based on an assumption of 5 g of daily salt intake. In 1998, the authors suspected that salt intake was more than 5 g and that pregnant women consumed more salt than non-pregnant women. Over 1,600 adults of both sexes were studied in five provinces. In this study we estimated salt intake based on urinary excretion of sodium and creatinine. A formula was used to calculate salt intake from excreted volumes of sodium and creatinine. Average values for pregnant women, non-pregnant women, and men, were found to be 15.6 g (n = 499), 12.6 g (n = 598), and 14.6 g (n = 571), respectively. We concluded that appropriate iodine content in salt should range from 20 to 40 PPM. It is recommended that health education regarding proper levels of salt intake be carried out with the general public, with emphasis on pregnant women. PMID- 11200215 TI - The content and efficacy of environmental public health journal homepages. AB - The information on several environmental public health journal homepages has been assessed for its quality and quantity, using selected key criteria. These criteria included the extent of text available, the ability to search the website, the table of contents free via email, and the presence of hyper-links. A high degree of variability is seen, with services and facilities offered ranging from none to the entire journal available for no fee. The journal homepages that are the most comprehensive are those that are associated with major institutions and hence financed by contributions from their members or public money, i.e. the British Medical Association, the World Health Organisation and the US National Institute of Environmental Health Sciences. The journal homepages associated with these institutions offered full text of both current and archived issues as well as additions such as the ability to search other sites, web links, and in some cases hyper-linked references and information on related articles. The provision of text on the Internet should be an essential aim for all journal Homepages, to ensure fast and effective conveyance of information to health professionals. PMID- 11200216 TI - A study on the effects of discotheque noise on the hearing of young patrons. AB - This study aims to find out whether discotheque music affects hearing by exposing 48 young volunteers to discotheque music in discotheque sessions at two discotheques and evaluating their degree of auditory fatigue after exposure. Questionnaire interviews revealed that the majority of them visit discotheques regularly. A higher proportion of those attending the louder discotheque found the music too loud. The prevalence of tinnitus is also higher in those attending the noisier discotheque. The degree of threshold shifts, however, does not appear to be related to the volume of music or auditory fatigue. The noise level exposure was estimated to be 91 dBA to 98 dBA for weekly exposure and 85 dBA to 92 dBA for monthly exposure. To avoid hearing loss, patrons should avoid loud discotheques, or cut down their frequency of visits if they choose to continue patronising them. PMID- 11200217 TI - Temporary overseas migration of rural Thai men: perception of changes in health and social interactions after returning to their communities. AB - A cross-sectional study was conducted to assess the perceived health effects of temporary overseas migration on rural Thai men and to evaluate the effects of financial gain on their social interactions with others. Houses in five villages in Khonkaen, northeastern Thailand were systematically visited and one returned overseas migrant per household was interviewed. One hundred and sixty one men participated in the study. Half of the respondents (50%) were manual workers. While overseas, 32% reported adverse effects of migration on their psychological health. Only 19% reported one or more physically ill while overseas. Their contribution to their communities increased. Inability to improve their financial status from overseas work is likely to have negative effects on the migrants' interaction with friends rather than their wives, families or relatives. The effects of migration on health are unlikely to persist after migrants return to their home communities. Overseas migration provides indirect health benefits through improvement of community facilities. PMID- 11200218 TI - Human immunodeficiency virus and hepatitis C virus infections among patients attending sexually transmitted disease clinics, Regional 2, Thailand. AB - A cross-sectional study of 400 patients attending sexually transmitted disease (STD) clinics at The Venereal Diseases and AIDS Centers, Regional 2, Thailand, was conducted from January to December 1996 in order to investigate the antibody prevalence to human immunodeficiency virus (HIV) and hepatitis C virus (HCV) and to describe some epidemiological characteristics among HIV and HCV co-infected individuals. The studied patients were interviewed and their blood specimens were collected for determining anti-HIV and anti-HCV antibodies. The results revealed that the prevalence of anti-HIV among studied patients was 25%, while 7.5% were positive for anti-HCV. The positivity of both antibodies present in the same individuals was 3.3% (13/400 cases). The highest prevalences of anti-HIV, anti HCV and both antibodies were found in studied patients aged 20 years or less. Patients with primary education, or lower, had relatively higher prevalence of anti-HIV and/or anti-HCV than those with higher level education. A relatively higher prevalence was found among commercial sex workers and labourers. Among 13 HIV and HCV co-infected individuals, there were four cases who had histories of sexual contact without condom use, but no history of parenteral contact. The rest (9/13) had histories of both parenteral contact and sexual contact without condom use. PMID- 11200219 TI - Suicide in Fiji: a review of the literature. AB - Clinical experience, public perceptions and research have indicated that the Indian community have been overrepresented in suicide statistics in Fiji. A computerised Medline search of the literature back to 1966 on suicide and ethnicity in Fiji using the search words SUICIDE and FIJI was performed supplemented by other relevant research and published material. A consistent pattern of higher suicide rates for the Indian population in Fiji compared to the indigenous Fijian population was found. Factors including religious and cultural beliefs, higher suicide risk in rural areas, use of toxic biocides as a method of suicide and relatively high suicide rates in young Indian women are discussed. Evidence for Indian vulnerability to suicide in Fiji has to date been based upon uncontrolled, descriptive observations. Helpful directions for future research include studying postulated vulnerability variables for suicide in the Indian community. PMID- 11200220 TI - A new light on the community health fund--effective political support for a community essential drug project in Vietnam. AB - This report sheds new light on the development of a community health fund through the implementation of a community essential drug project, and its impact on the improvement of primary health care at the community level. The experience of community drug funds in Vietnam, supported by a strong government commitment, in which full delegation of authority on the management of drugs and finances is given to the community along with a measure for tax exemptions for drug fund revenues, provides a significant example of an autonomous community with active participation of people and effective resource mobilization, that is leading to the improvement of community health. PMID- 11200221 TI - Phylogenetic analyses and comparative genomics of vitamin B6 (pyridoxine) and pyridoxal phosphate biosynthesis pathways. AB - Vitamin B6 in its active form pyridoxal phosphate is an essential coenzyme of many diverse enzymes. Biochemistry, enzymology and genetics of de novo vitamin B6 biosynthesis have been primarily investigated in Escherichia coli. Database searches revealed that the key enzymes involved in ring closure of the aromatic pyridoxin ring (PdxA; PdxJ) are present mainly in genomes of bacteria constituting the gamma subdivision of proteobacteria. The distribution of DXS, a transketolase-like enzyme involved in vitamin B6 biosynthesis as well as in thiamine and isoprenoid biosynthesis and the distribution of vitamin B6 modifying enzymes (PdxH: oxidase; PdxK: kinase) was also analyzed. These enzymes are also present in the genomes of animals. Two recent papers (Ehrenshaft et al., 1999, Proc. Natl. Acad. Sci. USA. 96: 9374-9378; Osmani et al., 1999, J. Biol. Chem. 274: 23565-23569) show the involvement of an extremely conserved protein (a member of the UPF0019 or SNZ family) found in all three domains of life (bacteria, archaea, eukarya) in an alternative vitamin B6 biosynthesis pathway. Members of this family were previously identified as a stationary phase inducible protein in yeast, as an ethylene responsible protein in plants and in a marine sponge, as a singlet oxygen resistance protein in Cercospora nicotianae and as a cumene hydroperoxide and H2O2 inducible protein in Bacillus subtilis. In yeast, the SNZ protein interacts with another protein called SNO which also represents a member of a highly conserved protein family (called UPF0030 or SNO family). Phylogenetic trees for the DXS, PdxA, PdxJ, PdxH, PdxK, SNZ and SNO protein families are presented and possible implications of the two different vitamin B6 biosynthesis pathways in cellular metabolism are discussed. A radically different view of bacterial evolution (Gupta, 2000, Crit. Rev. Microbiol. 26: 111-131) which proposes a linear rather than a treelike evolutionary relationship between procaryotic species indicates that the gamma subdivision of proteobacteria represents the most recently evolved bacterial lineage. This proposal might help to explain why the PdxA/PdxJ pathway is largely restricted to this subdivision. PMID- 11200222 TI - Phyloproteomics: species identification of Enterobacteriaceae using matrix assisted laser desorption/ionization time-of-flight mass spectrometry. AB - To evaluate matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS) as a tool for rapid identification of common clinical bacterial isolates, we analyzed 25 carefully selected isolates of pathogenic Escherichia coli (E. coli) and additional Enterobacteriaceae members. Organisms were prepared according to clinical microbiological protocols and analyzed with minimal additional processing. Spectra were reproducible from preparation to preparation and comprised 40-100 peaks primarily representing intracellular proteins with masses up to 25 kDa. Spectra of 14 genetically diverse bacteremic isolates of E. coli were compared with isolates representing other genera within the Enterobacteriaceae family. Using a new spectrum comparison algorithm, E. coli isolates were closely related to each other and were readily distinguishable from other Enterobacteriaceae, including Salmonella and Shigella. Presently, the methodology permits the analysis of 40 unknown isolates per hour per instrument. These results suggest that MALDI-ToF MS offers a rapid and reliable approach for performing phyloproteomics i.e., identification of unknown bacterial isolates based on similarities within protein biomarker databases. PMID- 11200223 TI - Organisation and evolution of the tol-pal gene cluster. AB - The genomic context and phylogenetic distribution of the tol-pal gene cluster and homologues to its various components have been investigated. The structure of this operon is well conserved across the gram negative bacteria, and the machine encoded by these genes probably evolved with the appearance of gram negative bacteria. Since the evolutionary appearance of the operon some species appear to have lost the genes. These bacteria seem to fall into two classes, namely obligate intracellular parasites and bacteria that produce large numbers of outer membrane vesicles. The evolution of the alphabeta and gamma proteobacteria was accompanied by the association of an additional gene (ybgC) with the operon. Several coincidences of genomic context argue for an important role of the tol pal operon in cell envelope maintenance. Genes homologous to tolQ and tolR proved to be very widespread being found throughout the eubacteria, and one example in the archea, this distribution argues for an ancient origin of these genes. The genomic context of these genes often suggests a role in micronutrient uptake. Interestingly in all the cases examined the tolQ and tolR genes or their homologues appear to be present as a pair, with a potential for a tight translational regulation. PMID- 11200224 TI - Reduction of wobble-position GC bases in Corynebacteria genes and enhancement of PCR and heterologous expression. AB - Corynebacteria codon usage exhibits an overall GC content of 67%, and a wobble position GC content of 88%. Escherichia coli, on the other hand has an overall GC content of 51%, and a wobble-position GC content of 55%. The high GC content of Corynebacteria genes results in an unfavorable codon preference for heterologous expression, and can present difficulties for polymerase-based manipulations due to secondary-structure effects. Since these characteristics are due primarily to base composition at the wobble-position, synthetic genes can, in principle, be designed to eliminate these problems and retain the wild-type amino acid sequence. Such genes would obviate the need for special additives or bases during in vitro polymerase-based manipulation and mutant host strains containing uncommon tRNA's for heterologous expression. We have evaluated synthetic genes with reduced wobble-position G/C content using two variants of the enzyme 2,5 diketo-D-gluconic acid reductase (2,5-DKGR A and B) from Corynebacterium. The wild-type genes are refractory to polymerase-based manipulations and exhibit poor heterologous expression in enteric bacteria. The results indicate that a subset of codons for five amino acids (alanine, arginine, glutamate, glycine and valine) contribute the greatest contribution to reduction in G/C content at the wobble position. Furthermore, changes in codons for two amino acids (leucine and proline) enhance bias for expression in enteric bacteria without affecting the overall G/C content. The synthetic genes are readily amplified using polymerase based methodologies, and exhibit high levels of heterologous expression in E. coli. PMID- 11200225 TI - Regulation of the early steps of 3-phenylpropionate catabolism in Escherichia coli. AB - Microbial catabolism of phenylpropanoid compounds plays a key role in the degradation of aromatic molecules originating from the degradation of proteins and plant constituents. In this study, the regulation of the early steps in the utilisation of 3-phenylpropionate, a phenylpropanoid compound, was investigated. Expression of the hcaA gene product, which is involved in 3-phenylpropionate catabolism in Escherichia coli, was positively regulated by HcaR, a regulatory protein similar to members of the LysR regulators family. Remarkably, the expression of hcaA in the presence of 3-phenylpropionate was sharply and transiently induced at the end of the exponential growth phase. This occurred in a rpoS-independent manner. This transient induction was also mediated by HcaR. The expression of this positive regulator is negatively autoregulated, as for other members of the LysR family. The expression of hcaR is strongly repressed in the presence of glucose. Glucose-dependent repression of hcaR expression could only be partially overcome by adding exogenous cAMP. PMID- 11200226 TI - Biosynthesis of K88 fimbriae in Escherichia coli: interaction of tip-subunit FaeC with the periplasmic chaperone FaeE and the outer membrane usher FaeD. AB - K88 fimbriae are ordered polymeric protein structures at the surface of enterotoxigenic Escherichia coli cells. Their production and assembly requires a molecular chaperone located in the periplasm (FaeE) and a molecular usher located in the outer membrane (FaeD). FaeC is the tip component of the K88 fimbriae. We studied the expression of the subcloned faeC gene, the subcellular localization of FaeC and its interaction with the chaperone and the outer membrane usher. In the absence of the chaperone or the usher, FaeC could not be detected in E. coli cells harbouring the faeC gene and its ribosome binding site under contol of the IPTG inducible lpp/lac promoter/operator. The expression of FaeC was detectable in the presence of chaperone FaeE, but a direct interaction between the chaperone and FaeC was not found. The expression of FaeC was also detectable in cells co expressing the outer membrane usher FaeD. Overexpression of FaeC after changing the faeC ribosome binding site appeared to induce lethality. Expression of subcloned FaeC in the absence of FaeE or FaeD could be detected when faeC was cloned under the tight control of the ara promoter/operator and when lethality induction was avoided. The direct interaction of FaeC with outer membranes containing the usher FaeD was studied by cell fractionation, isopycnic sucrose density gradient centrifugation, SDS-PAGE and immunoblotting. FaeC was found to bind to outer membranes containing FaeD or a FaeD-PhoA hybrid construct containing 215 amino-terminal residues of FaeD. This binding was not observed when control outer membranes without FaeD were used. No other K88 specific proteins were required for this interaction. The direct interaction between FaeC and FaeD in the outer membranes was shown by affinity blotting experiments. FaeE was not required for this interaction. Together these data indicate that the minor fimbrial subunit FaeC, unlike FaeG, H and F, does not have a strong interaction with the chaperone FaeE in the E. coli periplasm, but directly binds to the outer membrane molecular usher FaeD. PMID- 11200227 TI - Comparative genomics of prokaryotic GTP-binding proteins (the Era, Obg, EngA, ThdF (TrmE), YchF and YihA families) and their relationship to eukaryotic GTP binding proteins (the DRG, ARF, RAB, RAN, RAS and RHO families). AB - Several GTP-binding proteins with poorly defined functions were previously identified in Escherichia coli (i.e. Era, ThdF (TrmE)), Bacillus subtilis (i.e. Obg) and Neisseria gonorrhoeae (i.e. EngA). In these species, every individual protein is encoded by an essential gene. BLAST searches were used to detect orthologs in genomes of various organisms. Alignments of orthologous sequences allowed the construction of phylogenetic trees and the definition of protein families. The BLAST searches also resulted in the identification of two additional families, the YchF and YihA families, named after the ychF and yihA genes of E. coli. Most families are not present in archaeal genomes, but representatives of each family were also detected in eukaryotic genomes. Only representatives of the YchF family are present in every genome sequenced to date, suggesting that YchF-like proteins might be involved in a fundamental life process. The GTP1/DRG family consisting of eukaryotic and archaeal proteins is related to the YchF family of GTP-binding proteins. The relationship of the six prokaryotic families of GTP-binding proteins and the GTP1/DRG family to eukaryotic GTPase families was also investigated: With the exception of the ARF family, a clear separation of the six prokaryotic families and the GTP1/DRG family with respect to eukaryotic (RAB, RAN, RAS and RHO) GTPases was observed. PMID- 11200228 TI - Biology of Treponema pallidum: correlation of functional activities with genome sequence data. AB - Aspects of the biology of T. pallidum subsp. pallidum, the agent of syphilis, are examined in the context of a century of experimental studies and the recently determined genome sequence. T. pallidum and a group of closely related pathogenic spirochetes have evolved to become highly invasive, persistent pathogens with little toxigenic activity and an inability to survive outside the mammalian host. Analysis of the genome sequence confirms morphologic studies indicating the lack of lipopolysaccharide and lipid biosynthesis mechanisms, as well as a paucity of outer membrane protein candidates. The metabolic capabilities and adaptability of T. pallidum are minimal, and this relative deficiency is reflected by the absence of many pathways, including the tricarboxylic acid cycle, components of oxidative phosphorylation, and most biosynthetic pathways. Although multiplication of T. pallidum has been obtained in a tissue culture system, continuous in vitro culture has not been achieved. The balance of oxygen utilization and toxicity is key to the survival and growth of T. pallidum, and the genome sequence reveals a similarity to lactic acid bacteria that may be useful in understanding this relationship. The identification of relatively few genes potentially involved in pathogenesis reflects our lack of understanding of invasive pathogens relative to toxigenic organisms. The genome sequence will provide useful raw data for additional functional studies on the structure, metabolism, and pathogenesis of this enigmatic organism. PMID- 11200229 TI - Autoregulation of the biosynthesis of the CcpA-like protein, PepR1, in Lactobacillus delbrueckii subsp bulgaricus. AB - PepR1 from Lactobacillus delbrueckii subsp bulgaricus (Lb. bulgaricus) is involved in biosynthesis regulation of the prolidase PepQ. In this paper, we demonstrated that Lb. bulgaricus PepR1 biosynthesis is not constitutive like those of several bacteria but is auto-regulated and depends on the glucose concentration of the culture medium. We propose a model for PepQ regulation by PepR1. PMID- 11200230 TI - L-glutamate efflux with Corynebacterium glutamicum: why is penicillin treatment or Tween addition doing the same? PMID- 11200231 TI - Grouping together highly diverged PD-(D/E)XK nucleases and identification of novel superfamily members using structure-guided alignment of sequence profiles. AB - The PD-(D/E)XK nuclease domains, initially identified in type II restriction enzymes, serve as models for studying aspects of protein-DNA interactions, mechanisms of phosphodiester hydrolysis, and provide indispensable tools for techniques in genetic engineering and molecular medicine. However, the low degree of amino acid conservation hampers the possibility of identification of PD (D/E)XK superfamily members based solely on sequence comparisons. In several proteins implicated in DNA recombination and repair the restriction enzyme-like nuclease domain has been found only after the corresponding structures were determined experimentally. Here, we identified highly diverged variants of the PD (D/E)XK domain in many proteins and open reading frames using iterative database searches and progressive, structure-guided alignment of sequence profiles. We predicted the possible cellular function for many hypothetical proteins based on their relative similarity to characterized nucleases or observed presence of additional domains. We also identified the nuclease domain in genuine recombinases and restriction enzymes, whose homology to other PD-(D/E)XK enzymes has not been demonstrated previously. The first superfamily-wide comparative analysis, not limited to nucleases of known structure, will guide cloning and characterization of novel enzymes and planning new experiments to better understand those already studied. PMID- 11200232 TI - Protein-protein interaction between Bacillus stearothermophilus tyrosyl-tRNA synthetase subdomains revealed by a bacterial two-hybrid system. AB - We have recently developed a bacterial two-hybrid system (BACTH), based on functional complementation between two fragments of the catalytic domain of Bordetella pertussis adenylate cyclase (AC), that allows an easy in vivo screening and selection of functional interactions between two proteins in Escherichia coli. In this work, we have further explored the potentialities of the BACTH system to study protein-protein interactions, using as a model, the interactions between various subdomains of the dimeric tyrosyl-tRNA synthetase (TyrRS) of Bacillus stearothermophilus. Using the BACTH system we confirmed the known interactions of the alpha/beta domains and those between the alpha/beta domain and the alpha domain that could be anticipated from the three-dimensional structure of TyrRS. Interestingly, the BACTH system revealed the unexpected interaction between the TyrRS alpha domains which is presumably mediated by a pseudo-leucine zipper motif. This study illustrates the interest of the bacterial two-hybrid system to delineate interacting domains of proteins and shows that it can reveal interactions that occur in vivo and that were not anticipated from the three-dimensional structure of the protein of interest. PMID- 11200233 TI - OspA, a lipoprotein antigen of the obligate intracellular bacterial pathogen Piscirickettsia salmonis. AB - No effective recombinant vaccines are currently available for any rickettsial diseases. In this regard the first non-ribosomal DNA sequences from the obligate intracellular pathogen Piscirickettsia salmonis are presented. Genomic DNA isolated from Percoll density gradient purified P. salmonis, was used to construct an expression library in lambda ZAP II. In the absence of preexisting DNA sequence, rabbit polyclonal antiserum raised against P. salmonis, with a bias toward P. salmonis surface antigens, was used to identify immunoreactive clones. Catabolite repression of the lac promoter was required to obtain a stable clone of a 4,983 bp insert in Escherichia coli due to insert toxicity exerted by the accompanying radA open reading frame (ORF). DNA sequence analysis of the insert revealed 1 partial and 4 intact predicted ORF's. A 486 bp ORF, ospA, encoded a 17 kDa antigenic outer surface protein (OspA) with 62% amino acid sequence homology to the genus common 17 kDa outer membrane lipoprotein of Rickettsia prowazekii, previously thought confined to members of the genus Rickettsia. Palmitate incorporation demonstrated that OspA is posttranslationally lipidated in E. coli, albeit poorly expressed as a lipoprotein even after replacement of the signal sequence with the signal sequence from lpp (Braun lipoprotein) or the rickettsial 17 kDa homologue. To enhance expression, ospA was optimized for codon usage in E. coli by PCR synthesis. Expression of ospA was ultimately improved (approximately 13% of total protein) with a truncated variant lacking a signal sequence. High level expression (approximately 42% tot. prot.) was attained as an N-terminal fusion protein with the fusion product recovered as inclusion bodies in E. coli BL21. Expression of OspA in P. salmonis was confirmed by immunoblot analysis using polyclonal antibodies generated against a synthetic peptide of OspA (110 129) and a strong antibody response against OspA was detected in convalescent sera from coho salmon (Oncorhynchus kisutch). PMID- 11200235 TI - Nutritional support in the intensive care unit: are patients receiving what is prescribed? PMID- 11200234 TI - A sigmaB-like factor responsible for carotenoid biosynthesis in Streptomyces griseus. AB - Self-cloning experiments with a high-copy-number plasmid and Streptomyces griseus IFO13350 led to the cloning of a 11-kb DNA fragment that conferred yellow pigment production on the host. The cloned fragment contained a gene cluster for carotenoid biosynthesis, in which two polycistrons, crtE (encoding geranylgeranyl pyrophosphate synthase)-crtI (phytoene dehydrogenase)-crtB (phytoene synthase) crtV (functionally unknown methyltransferase-like protein) and crtY (lycopene cyclase)-crtT (functionally unknown methyltransferase-like protein)-crtU (beta carotene dehydrogenase), were present in a convergent way. Since strain IFO13350 produced no detectable amount of carotenoids, an increase in the copy number of the crt gene cluster led to production of carotenoids at a detectable level. Overexpression of the stress-responsive sigmaB-like protein CrtS from Streptomyces setonii also activated the cryptic crt genes in S. griseus and conferred pigmentation. A CrtS homologue (sigmaCrtS) in S. griseus, which was predicted by a computer-aided homology search, caused carotenogenesis to the same extent as CrtS of S. setonii, indicating that the two sigmaB-like proteins were functionally the same. Yellow pigment production by S. griseus containing crtS under the control of a strong promoter on a high-copy-number plasmid resulted from activation of transcription of the crt genes, because overexpression of sigmaCrtS in S. griseus led to transcriptional activation of the promoters in front of crtE and crtY. S1 nuclease mapping showed that crtS itself was transcribed at a low level under the laboratory conditions, which may account for undetectable production of carotenoids. The crt genes were suggested to locate very near one end of the linear chromosome, since they were completely deleted in mutant HH1 having large deletions at both ends. The gene organization of crt in S. griseus is similar to that in S. coelicolor A3(2) where the whole crt gene set is near one end of the chromosome. PMID- 11200236 TI - Combined procoagulant and innate immune responses to infection: toward more potent drugs in septic patients. PMID- 11200237 TI - Intensive care unit frequent fliers: morbidity and cost. PMID- 11200238 TI - Daily versus admission mortality estimates: is admission severity yesterday's news? PMID- 11200239 TI - Acute respiratory distress syndrome: different syndromes, different therapies? PMID- 11200240 TI - Tempering the temptation to treat with tempol. PMID- 11200241 TI - Modulating nitric oxide synthesis: another contender enters the ring. PMID- 11200242 TI - Unilateral withdrawal of life-sustaining therapy: is it time? Are we ready? PMID- 11200243 TI - Conflict over communication and unprofessional staff behavior: a common source of dissatisfaction during the withdrawal of care? PMID- 11200244 TI - Axonal injury is accentuated in the caudal corpus callosum of head-injured patients. AB - Amyloid precursor protein (APP) accumulation is a sensitive marker for the axonal damage that is commonly seen in the brain as the result of head injury. This form of damage is particularly associated with midline structures such as the corpus callosum, although it is not clear whether some areas are more susceptible than others. The aim of this study was to determine if there was a differential distribution of axonal injury throughout the corpus callosum after head injury in an unselected group of cases. Coronal tissue sections from eight cases were taken at different levels through the corpus callosum, including the genu, body, and splenium. The sections were immunostained with an antibody to APP, and the amount of axonal damage at the different levels was quantified using computer image analysis to build up a rostro-caudal profile for each case. The profiles revealed a significantly higher APP load in caudal parts of the corpus callosum. This supports previous nonquantitative reports in the literature and has important implications in terms of choosing where tissue should be sampled to maximize the chance of detecting axonal injury post mortem. PMID- 11200245 TI - Improved recovery after spinal cord injury in neuronal nitric oxide synthase deficient mice but not in TNF-alpha-deficient mice. AB - Wild-type mice and mice lacking nitric oxide synthase (NOS) of neuronal type or TNF-alpha were subjected to an extradural compression of the thoracic spinal cord. The functional outcome of the hind limbs was assessed by using a motor function score (MFS). The injury resulted in paraplegia of the hind limbs in wild type mice at day 1 after injury. Gradual recovery was observed during the following 14 days. Injured NOS -/- animals had an improved hind limb motor function during the entire observation period compared to wild-type controls. The difference was statistically significant on day 10 (p < 0.022) and day 14 (p < 0.048) after injury. At the site of injury, there was a trend of gray matter preservation in NOS -/- mice, as measured by MAP2 staining (p < 0.077). Injured mice lacking TNF-alpha had the lowest motor score among all the groups on day 1. During the following period, they had motor scores similar to those of wild-type controls and there was no significant difference at any time point. TNF-alpha -/- animals showed a trend of decreased white matter preservation compared to wild type animals (p < 0.097). Our study shows that after spinal cord injury, mice lacking NOS have a better functional ability of their hind limbs than controls with the same degree of injury. This would indicate that the functional outcome is influenced in a negative way in wild mice by the presence of NO. The degree of secondary damage to the spinal cord might be attenuated in NOS-deficient mice. PMID- 11200246 TI - The neuropsychology of blunt head injury in the early postacute stage: effects of focal lesions and diffuse axonal injury. AB - This investigation evaluated the neuropsychological symptoms in the early posttraumatic period following blunt head injury and their correlation to routine imaging data in a consecutive series of TBI patients (Magdeburg Neurotrauma Databank). Of 135 consecutive patients, 68 could be assessed neuropsychologically 8-21 days after trauma. In 61 patients, routine clinical CT data were sufficient for neuroradiological analysis focusing on the presence or absence of CT signs of diffuse axonal injury (DAI) or focal traumatic injury. In these patients, the initial GCS score was significantly correlated with the presence of DAI but not with focal pathology. The presence of DAI was correlated with behavioral and cognitive symptoms of frontal lobe dysfunction, especially in interference tasks (Go/NoGO and Stroop reaction times) and semantic fluency. The presence of local frontal or temporal traumatic lesions was associated with deficits in concept formation, fluency tasks and behavioral symptoms, but not with increased interference. Patients with frontal contusions were impaired in a task of visuomotor planning and performance (Block design). Our data indicate that both traumatic DAI and focal lesions result in frontal lobe symptoms. We conclude that, even in clinically "mild" TBI, brain imaging should be used to identify patients with substantial brain damage. These should be assessed neuropsychologically for possible posttraumatic cognitive or behavioral impairment. In consideration of its easy accessibility, the refined use of the CT is considered a promising and valid tool for patient stratification. The application of MRI and biochemical markers may further improve prognostic predictions. PMID- 11200247 TI - Comparison of brain responses between frontal and lateral impacts by finite element modeling. AB - This study was conducted to investigate differences in brain response due to frontal and lateral impacts based on a partially validated three-dimensional finite element model with all essential anatomical features of a human head. Identical impact and boundary conditions were used for both the frontal and lateral impact simulations. Intracranial pressure and localized shear stress distributions predicted from these impacts were analyzed. The model predicted higher positive pressures accompanied by a relatively large localized skull deformation at the impact site from a lateral impact when compared to a frontal impact. Lateral impact also induced higher localized shear stress in the core regions of the brain. Preliminary results of the simulation suggest that skull deformation and internal partitions may be responsible for the directional sensitivity of the head in terms of intracranial pressure and shear stress response. In previous experimental studies using subhuman primates, it was found that a lateral impact was more injurious than a frontal impact. In this study, shear stress in the brain predicted by the model was much higher in a lateral impact in comparison with a frontal impact of the same severity. If shear deformation is considered as an injury indicator for diffuse brain injuries, a higher shear stress due to a lateral impact indicate that the head would tend to have a decreased tolerance to shear deformation in lateral impact. More research is needed to further quantify the effect of the skull deformation and dural partitions on brain injury due to impacts from a variety of directions and at different locations. PMID- 11200249 TI - Subtle alterations in NMDA-stimulated cyclic GMP levels following lateral fluid percussion brain injury. AB - This study examined whether NMDA-stimulated cyclic GMP levels were altered at two different time points following lateral fluid percussion injury. At 60 min and 15 days postinjury, the left and right hippocampi were dissected and chopped into mini-prisms. Each hippocampus was divided into five equal parts and incubated with either the phosphodiesterase inhibitor IBMX (3-isobutyl-1-methylxanthine, 500 microM) alone, IBMX and N-methyl-D-aspartic acid (NMDA) OR IBMX, NMDA, and glycine (10 MM). Two concentrations of NMDA were used: 500 or 1,000 microM. Tissues were then assayed for levels of cyclic GMP. Results indicated that there were no changes in basal levels of cyclic GMP at either postinjury time point. At 60 min postinjury, there were no significant main effects for injury or drug concentration. There was a significant injury x side interaction effect with increased levels of NMDA-stimulated cyclic GMP in the hippocampus ipsilateral to the injury impact and decreased cyclic GMP levels in the contralateral hippocampus. There were no significant alterations in NMDA-stimulated cyclic GMP levels at 15 days postinjury. The data from this study indicated that NMDA stimulated cyclic GMP accumulation is differentially altered in the hippocampus ipsilateral and contralateral to the site of the injury at 1 h after injury, but is normalized by 15 days postinjury. These findings implicate NMDA-mediated intracellular signaling processes in the acute excitotoxic response to injury. PMID- 11200248 TI - Mapping cerebral glucose metabolism during spatial learning: interactions of development and traumatic brain injury. AB - Previous studies have demonstrated that, compared to adults, postnatal day 17 (P17) and P28 rats show remarkable cognitive recovery in the Morris water maze (MWM) following fluid percussion injury (FPI). This observed age-at-trauma effect could result from either younger animals solving the MWM task using noninjured neural circuitry or an inability of adult and P28 brains to activate appropriate neural networks due to trauma-induced neurological dysfunction. To address these possibilities, we compared "activated" brain regions during normal MWM acquisition and following FP injury. To generate "activated" images of the brain while animals were performing the MWM task, qualitative [14C]2-deoxy-D-glucose was conducted on days 2, 5, and 14 during training in sham and injured adult, P28, and P17 rats. When maturational changes in cerebral glucose metabolism are taken into account, the results suggests similar activity changes in the cerebral cortex and lacunosum moleculare of CA1 during acquisition in all age groups, suggesting that the developmental rates of MWM learning do not correspond to different patterns of activated cerebral metabolism. Injured P17s, showing no latency deficits, revealed activated cerebral metabolic patterns similar to noninjured P17 animals. In P28 and adult cases, animals exhibited cognitive deficits and their metabolic studies indicated that the cortical-hippocampal pattern of activation was disrupted by marked injury-induced metabolic depression, which primarily affected the ipsilateral hemisphere and lasted for as long as 14 days in adult animals. PMID- 11200250 TI - The impact of hypercarbia on the evolution of brain injury in a porcine model of traumatic brain injury and systemic hemorrhage. AB - Carbon dioxide is perhaps the most potent available modulator of cerebrovascular tone and thus cerebral blood flow (CBF). These experiments evaluate the impact of induced hypercarbia on the matching of blood flow and metabolism in the injured brain. We explore the hypothesis that hypercarbia will restore the relationship of CBF to metabolic demand, resulting in improved outcome following traumatic brain injury (TBI) and hemorrhage. A behavioral outcome score, hemodynamic, metabolic, and pathologic parameters were assessed in anesthetized and ventilated juvenile pigs. Animals were assigned to either normocarbia or hypercarbia and subdivided into TBI (via fluid percussion) with or without hemorrhage. The experimental groups were TBI; TBI + 40% hemorrhage (40%H); TBI + hypercarbia (CO2); and TBI + 40%H + CO2. Hemorrhaged animals were resuscitated with blood and crystalloid. Hypercarbia was induced immediately following TBI using 10% FiCO2. The normocarbic group demonstrated disturbance of the matching of CBF to metabolism evidenced by statistically significant increases in cerebral oxygen and glucose extraction. Hypercarbic animals showed falls in the same parameters, demonstrating improvement in the matching of CBF to metabolic demand. Parenchymal injury was significantly decreased in hypercarbic animals: 3/10 hypercarbic versus 6/8 normocarbic animals showed cerebral contusions at the gray/white interface (p = 0.05). The hypercarbic group had significantly better behavioral outcome scores, 10.5, versus 7.3 for the normocarbic groups (p = 0.005). The decreased incidence of cerebral contusion and improved behavioral outcome scores in our experiments appear to be mediated by better matching of cerebral metabolism and blood flow, suggesting that manipulations modulating the balance of blood flow and metabolism in injured brain may improve outcomes from TBI. PMID- 11200251 TI - Adenovirus-mediated transfer and expression of beta-gal in injured hippocampus after traumatic brain injury in mice. AB - In models of focal cerebral ischemia, adenoviral gene transfer is often attenuated or delayed versus naive. After controlled cortical impact (CCI) induced traumatic brain injury in mice, CA1 and CA3 hippocampus exhibit delayed neuronal death by 3 days, with subsequent near complete loss of hippocampus by 21 days. We hypothesized that adenoviral-mediated expression of the reporter gene beta-Galactosidase (beta-Gal) in hippocampus would be attenuated after CCI in mice. C57BL6 mice (n = 16) were subjected to either CCI to left parietal cortex or sham (burr hole). Adenovirus carrying the beta-Gal gene (AdlacZ; 1 x 10(9) plaque-forming units [pfu]/mL) was then injected into left dorsal hippocampus. At 24 or 72 h, beta-Gal expression was quantified (mU/mg protein). Separate mice (n = 10) were used to study beta-Gal spatial distribution in brain sections. Beta Gal expression in left hippocampus was similar in shams at 24 h (48.4 +/- 4.1) versus 72 h (68.8 +/- 8.8, not significant). CCI did not reduce beta-Gal expression in left hippocampus (68.8 +/- 8.8 versus 88.1 +/- 7.0 at 72 h, sham versus CCI, not significant). In contrast, CCI reduced beta-Gal expression in right (contralateral) hippocampus versus sham (p < 0.05 at both 24 and 72 h). Beta-Gal was seen in many cell types in ipsilateral hippocampus, including CA3 neurons. Despite eventual loss of ipsilateral hippocampus, adenovirus-mediated gene transfer was surprisingly robust early after CCI providing an opportunity to test novel genes targeting delayed hippocampal neuronal death. PMID- 11200252 TI - Characteristics of sustained blood-brain barrier opening and tissue injury in a model for focal trauma in the rat. AB - Minor stab wounding of rodent brain by needle or razor blade is a standard model for immunohistochemical investigations of secondary neuronal degeneration and scarring. Opening of the blood-brain barrier (BBB) to plasma molecules and inflammatory cells is integral to the secondary injury process. To facilitate quantitative study of these BBB phenomena, we tested the utility of a stereotaxic wire knife as a minimally invasive way for modeling of focal trauma and bleeding in brain parenchyma and substantial, reproducible BBB damage. Adult rats were anesthetized, and through a skull burr hole, the 0.3-mm dia guide cannula housing a laterally extendable tungsten wire (0.13 mm dia) was inserted into the right striatum. A layering of horizontal disk-like cuts (3 mm dia) was made, producing a cylindrical lesion of approximately 18 mm3 volume, approximately 2.7% of the cerebral hemisphere. Transfer constants (Ki) for blood to brain permeation of [3H]sucrose measured from 30 min to 2 weeks postlesion showed sustained BBB leakiness; for example, mean Ki +/- SEM (nL.g(-1) x s(-1)) for a standard, matrix dissected forebrain sample enclosing the lesion were 7.2 +/- 1.2 (day 1 postlesion), 8.1 +/-1.4 (day 3), 5.4 +/- 0.8 (day 14) compared with values for contralateral nonlesioned forebrain ranging from 1.3 +/- 0.05 to 1.6 +/- 0.3 (n = 3-4 samples per time point). Analysis of the simultaneous transport of [14C]sucrose (MW = 342 Da) and [3H]inulin (MW approximately 5,000) showed significantly larger upward increments in Ki for sucrose than inulin, indicating a pore-like opening mechanism. Significant edema was measured 3 days postlesion. A reactive glial response was indicated by an increase in S100beta by 6 h and a glial scar forming around the lesion by 7 days. Secondary brain injury was indicated by a 10% loss of hemisphere mass, measured at 2 months. The wire knife enabled tailoring of interstitial trauma with a minimum of extraneous injury and supported reproducible measurements of sustained BBB injury using relatively few animals. PMID- 11200253 TI - Preventive effects of lecithinized superoxide dismutase and methylprednisolone on spinal cord injury in rats: transcriptional regulation of inflammatory and neurotrophic genes. AB - The effects of lecithinized superoxide dismutase (PC-SOD) and/or methylpredisolone (MP) in preventing secondary pathological changes after spinal cord injury (SCI) were investigated in rats with reference to recovery of hindlimb motor function and expression of mRNA of pro-inflammatory and neurotrophic genes. Hindlimb motor function was assessed as the BBB open field locomotor scores. The BBB scores of three groups treated with either PC-SOD (40,000 units/kg), MP (30 mg/kg), or a combination of PC-SOD and MP (PC-SOD+MP) increased with time until 3 days after SCI, and were significantly higher than that of the control group (p < 0.05). Thereafter, the score of the PC-SOD group increased, whereas that of the MP group showed a temporary decrease from day 3 to 5 and then it gradually recovered. The scores in all groups reached a plateau about 18 days after SCI. The PC-SOD+MP group did not show a synergism but a tendency similar to that of the MP group. PC-SOD and MP had down-regulatory effects on mRNA expression of pro-inflammatory substances such as interleukin 1beta (IL-1beta), intercellular adhesion molecule-1 (ICAM-1), and inducible nitric oxide synthetase (i-NOS) after spinal cord compression at 3, 6, and 24 h, respectively, as judged by a semiquantitative reverse transcription-polymerase chain reaction and on the lipid peroxide (LPO) level 1 h after injury as determined by thiobarbituric acid-reactive substances. The suppression of pro inflammatory genes expression, especially IL-1beta were greater in the MP group than in the PC-SOD group, while suppression of LPO level was similar in these two groups. PC-SOD+MP treatment augmented the suppression of all three pro inflammatory genes expression and the decrease of the LPO level. The level of neurotrophin-3 (NT-3) mRNA increased from 6 h after SCI and reached a maximum after 48 h. NT-3 mRNA level was enhanced by PC-SOD treatment, but not by MP treatment. Thus, the effect of MP in suppressing these pro-inflammatory genes expression was more than that of PC-SOD. The difference in motor function in the early and later stage may be partially due to differences in expression of IL 1beta and NT-3 after either treatment, through an IL-1beta-dependent or NT-3 mediated repair response. PMID- 11200254 TI - Studies on reactions of nucleoside H-phosphonates with bifunctional reagents. Part VI. Reaction with diols. AB - Reactions of nucleoside H-phosphonates with various diols using different types of condensing agents have been studied. Depending on the coupling procedure and the length of a polymethylene chain of the diol, acyclic H-phosphonate diesters or cyclic phosphite triesters were formed. The course of oxidation with iodine to produce cyclic nucleoside alkyl phosphotriesters or hydroxyalkyl nucleoside phosphodiesters can be controlled by the amount of water present in the reaction medium. PMID- 11200256 TI - Synthesis and antiviral evaluation of the beta-L-enantiomers of some thymine 3' deoxypentofuranonucleoside derivatives. AB - 3'-Deoxy-beta-L-erythro- (3), 3'-deoxy-beta-L-threo- (6), 2'-fluoro- (7) and 2' azido-2',3'-dideoxy-beta-L-erythro- (10) pentofuranonucleoside derivatives of thymine have been synthesized and their antiviral properties examined. All these derivatives were stereospecifically prepared by glycosylation of thymine with a suitable peracylated 3-deoxy-L-erythro-pentofuranose sugar (1), followed by appropriate chemical modifications. The prepared compounds were tested for their activity against HIV, but they did not show an antiviral effect. PMID- 11200255 TI - The mechanism of DNA repair by uracil-DNA glycosylase: studies using nucleotide analogues. AB - 2',4'-Dideoxy-4'-methyleneuridine incorporated into oligodeoxynucleotides forms regular B-DNA duplexes as shown by Tm and CD measurements. Such oligomers are not cleaved by the DNA repair enzyme, UDG, which cleaves the glycosylic bond in dU but not in dT nor in dC nucleosides in single stranded and double stranded DNA. Differential binding of oligomers containing carbadU, 4'-thiodU, and dU residues to wild type and mutant UDG proteins identify an essential role for the furanose 4'-oxygen in recognition and cleavage of dU residues in DNA. PMID- 11200257 TI - Guanosine analogues as anti-herpesvirus agents. AB - Several guanosine analogues, i.e. acyclovir (and its oral prodrug valaciclovir), penciclovir (in its oral prodrug form, famciclovir) and ganciclovir, are widely used for the treatment of herpesvirus (i.e. HSV-1, HSV-2, VZV and HCMV) infections. In recent years, several new guanosine analogues have been developed, including the 3-membered (cyclopropyl) sugar derivative A-5021 and the 6-membered D- and L-cyclohexenyl derivatives. Prominent features shared by all guanosine analogues are the following. They depend for their phosphorylation on the virus encoded thymidine kinase (TK), which makes them particularly effective against those viruses (HSV-1, HSV-2 and VZV) that encoded for such TK. They are also active against HCMV, whether or not they are subject of phosphorylation by the HCMV-induced UL97 protein kinase. Their antiviral activity can be markedly potentiated by mycophenolic acid, an IMP dehydrogenase inhibitor, and they hold great promise, not only as antiviral agents for the treatment of herpesvirus infections, but also as antitumor agents for the combined gene therapy/chemotherapy of cancer, provided that (part of) the tumor cells have been transfected by the viral TK gene. PMID- 11200258 TI - Synthesis and properties of 2'-deoxycytidine triphosphate carrying c-myc tag sequence. AB - The synthesis of 2'-deoxycytidine triphosphate carrying mercaptoethyl groups at position 4 of cytosine is described. This nucleoside triphosphate was reacted with a maleimido-peptide carrying the c-myc tag-sequence to yield a peptide nucleoside triphosphate chimera. Primer extension studies showed that the nucleoside triphosphate modified with the peptide sequence is incorporated by DNA polymerases opposite guanine. PMID- 11200259 TI - A remarkable stabilization of complexes formed by 2,6-diaminopurine oligonucleotide N3'-->P5' phophoramidates. AB - 2'-Deoxyribo- and ribo-oligonucleotide N3'-->P5'phosphoramidates containing 2,6 diaminopurine nucleosides were synthesized. Thermal denaturation experiments demonstrated a significant stabilization of the complexes formed by these compounds with DNA and RNA complementary strands, relative to adenosine containing phosphoramidate counterparts. The increase in melting temperature of the complexes reached up to 6.9 degrees C per substitution. The observed stabilization was attributed to the apparent synergistic effects of N-type sugar puckering of the oligonucleotide N3'-->P5' phosphoramidate backbone, and the ability of 2,6-diaminopurine bases to form three hydrogen bonds. PMID- 11200260 TI - Transglycosylation reactions of 6-thioguanine acyclonucleosides. AB - 9-(2-Acetoxyethoxy)methyl-N2-acetyl-6-thoguanine (2) undergoes two different transglycosylation reactions: i) the 7<=>9 isomerization, which gives the respective 7-regioisomer (3) as the major product, ii) the 9<=>S6 glycosyl migration, which leads to a 9,S6-disubstituted product (4). S6-Methylation completely stopped the reversibility of transglycosylation. PMID- 11200261 TI - Fluorescence properties and base pair stability of oligonucleotides containing 8 aza-7-deaza-2'-deoxyisoinosine or 2'-deoxyisoinosine. AB - The fluorescence and the base pairing properties of 8-aza-7-deaza-2' deoxyisoinosine (1) are described and compared with those of 2'-deoxyisoinosine (2). The corresponding phosphoramidites (11, 12) are synthesized using the diphenylcarbamoyl (DPC) residue for the 2-oxo group protection. The nucleosides 1 and 2 base pair with 2'-deoxy-5-methylisocytidine in DNA duplexes with antiparallel chain orientation and with 2'-deoxycytidine in a parallel DNA. These base pairs are less stable than the canonical dA-dT pair and that of 2' deoxyinosine (4) with 2'-deoxycytidine. The fluorescence of the nucleosides 1 and 2 is quenched (approximately 95%) in duplex DNA. The residual fluorescence is used to determine the Tm-values, which are found to be the same as determined UV spectrophotometrically. PMID- 11200262 TI - Synthesis and incorporation of pyrrole carboxamide nucleoside triphosphates by DNA polymerases. AB - We have synthesised and examined the enzymatic incorporation properties of the 5' triphosphates of 2'-deoxyribosyl pyrrole 3-monocarboxamide (dMTP) and 2' deoxyribosyl pyrrole 3,4-dicarboxamide (dDTP). These analogues we had hoped would behave as ambivalent base analogues in that they can present two alternative hydrogen-bonding faces either by rotation about the carboxamide group or about the glycosidic bond. The two pyrrole derivatives, dMTP and dDTP, exhibit a preference for incorporation with Klenow polymerase. They are preferentially incorporated as either A or C. PMID- 11200263 TI - The synthesis of deuterionucleosides. AB - The synthesis of deuterionucleosides for site-specific incorporation into oligo DNA or -RAA is herein reviewed for NMR or biological studies. The review covers the following aspects: (i) deuteration of the aglycone; (ii) single-site chemical deuteration of the sugar residues; (iii) multiple-site chemical deuteration of the sugar residues; (iv) enzymatic synthesis of deuterated nucleosides or nucleotides; and (v) synthesis of labelled nucleosides with multiple isotopes PMID- 11200264 TI - Nucleophilic N1-->N3 rearrangement of 5'-O-trityl-O2,3'-cycloanhydrothymidine. AB - 5'-O-Trityl-O2,3'-cycloanhydrothymidine (1) heated at 150 degrees C in the presence of O,O-diethyl phosphate or O,O-diethyl phosphorothioate anions undergoes rearrangement into N3-isomer (2); its structure was established by both advanced NMR methods and X-ray crystallographic studies. The most probable mechanism of 1-->2 rearrangement relies upon reversibility of glycosidic bond cleavage process. PMID- 11200265 TI - Cleavage of the phosphodiester bond of uridylyl-(3',5')-8 carboxymethylaminoadenosine by hydronium, hydroxide and zinc(II) ions: a model study aimed at elucidating the potential of a carboxylate function as an intramolecular catalyst. AB - Uridylyl-(3',5')-8-carboxymethylaminoadenosine has been synthesised, and its transesterification to uridine 2',3'-cyclic phosphate in the presence and absence of Zn2+ ion has been studied. The results show that a carboxylate function in the vicinity of the phosphodiester bond accelerates the metal ion promoted cleavage but not the metal ion independent reaction. Under acidic conditions, the predominant reaction is the cleavage of the side chain, giving the 8-amino derivative. PMID- 11200266 TI - Synthesis of modified nucleotide building blocks containing electrophilic groups in the 2'-position. AB - Chemical syntheses of 2'-O-(allyloxycarbonyl)methyladenosine, 2'-O (methoxycarbonyl)methyladenosine and 2'-O-(2,3-dibenzoyloxy)propyluridine 3'-2 cyanoethyl-N,N-diisopropyl phosphoramidite building blocks are described. These monomers were used successfully to incorporate carboxylic acid, 1,2-diol and aldehyde functionalities into synthetic oligonucleotides. PMID- 11200267 TI - Antisense phosphorothioate oligonucleotides targeted to the human chemokine receptor CXCR4. AB - The CXC chemokine receptor CXCR4 is used as a major co-receptor for fusion and entry by syncytia-inducing T-tropic (X4) isolates of HIV-1. In the present study, we report the effects of an antisense oligodeoxyribonucleotide on the inhibition of CXCR4 gene expression in X4 HIV-1 infected HeLa-CD4 cells, to find more efficacious therapeutic possibilities for Human Immunodeficiency Virus type 1 (HIV-1) infection. Antisense phosphorothioate oligodeoxyribonucleotides (anti-S ODNs) corresponding to the sequence of bases 69 to 88 of the human CXCR4 mRNA gene were synthesized. When the naked anti-S-ODN was incubated with HeLa-CD4 cells, the surface levels of this chemokine receptor were reduced up to 50%, indicating sequence-specific inhibition. We also examined the concomitant use of a basic peptide transfection reagent, nucleosomal histone proteins (RNP), for delivery of anti-S-ODNs. The anti-S-ODN encapsulated with RNP had higher inhibitory effects on p24 products than the naked anti-S-ODN. PMID- 11200268 TI - Anti-HIV-1 activity by a triple-helix forming oligonucleotides targeted to polypurine tract on viral RNA. AB - Reverse transcription of HIV-1 into double-stranded DNA involves initiation of plus-strand DNA synthesis at the polypurine tract, PPT, by reverse transcriptase (RT). The PPT is a possible target for triple-helix formation. We show the effects of triple-helix formation by assays of RNase H cleavage inhibition in vitro using two systems (two-strand-system (FTFOs) or three-strand-system (TFOs)) targeted to the polypurine tract (PPT) of HIV-1. The two-stranded composition of a triple-helix is thermodynamically and kinetically superior to the three-strand system. The FTFOs inhibited the RNase H activity in a sequence-specific manner, i.e., the triplex actually formed at the PPT and blocked the RNase H. The FTFOs containing the phosphorothioate groups at the antisense strand showed greater 3' exonuclease resistance. In HIV-1 infected MT-4 cells, the FTFOs containing the phosphorothioate groups at the antisense strand and guanosine rich parts within the third Hoogsteen base pairing sequence inhibit the replication of HIV-1 more effectively than the antisense phosphorothioate oligonucleotides, indicating sequence-specific inhibition of HIV-1 replication. PMID- 11200269 TI - Fluorescent alpha-anomeric 1,N(6)etheno-deoxyadenosine in DNA duplexes. The alpha epsilondA / dG pair. AB - Structural properties of the fluorescent alpha-anomeric 1,N(6)ethenodeoxyadenosine residue placed in opposition to all four canonical deoxynucleotide units within 11-mer DNA duplexes have been studied. The duplex with alpha-epsilondA / dG pairing is most thermodynamically stable while the alpha-epsilondA / dC one is the least stable. Fluorescence measurements confirm the thermodynamic data and indicate base-pair dependent stacking properties of alpha-epsilondA within duplex structures. Results of molecular dynamics (MD) simulations in aqueous solution for the most stable duplex point to the presence of different conformational states of the alpha-1,N(6)etheno-deoxyadenosine residue, including formation of a hydrogen bonded pair with the dG and possible occurrence of severe kinking in the duplex. PMID- 11200270 TI - New phosphoramidite reagents for the synthesis of oligonucleotides containing a cysteine residue useful in peptide conjugation. AB - The preparation is described of four 2-cyanoethyl-N,N-diisopropyl phosphoramidites of N-alpha-Fmoc-S-protected cysteine hydroxyalkyl amides. The phosphoramidites were used in solid-phase synthesis of 5'-cysteinyl oligonucleotides, useful intermediates in the preparation of peptide oligonucleotide conjugates through reaction with a maleimide peptide or with a peptide thioester via "native ligation". PMID- 11200271 TI - Nucleotides LXIV[1]: synthesis hydridization and enzymatic degradation studies of 2'-O-methyloligoribonucleotides and 2'-O-methyl/deoxy gapmers. AB - 2'-O-Methyloligoribonucleotides, deoxyoligonucleotides and 2'-O-methyl/deoxy gapmers were synthesized using solid phase phosphoramidite chemistry employing the 2-(4-nitrophenyl)ethyl (npe) protection strategy. Melting temperatures of the synthesized oligonucleotides as well as their stability against degradation by several different nucleases were determined. 2'-O-Methyloligoribonucleotides showed the highest melting temperatures (Tm's) whereas 2'-O-methyl/deoxy gapmers revealed either slightly higher or surprizingly no thermal stabilities compared with their deoxy analogs when using self-complementary sequences. Gapmers with four 2'-O-methyl nucleotides on both ends showed about the same stability as all 2'-O-methyloligoribonucleotides against micrococal nuclease, nuclease S1, and snake venom phosphodiesterase. PMID- 11200272 TI - New efficient synthesis of thymidine cyclic 3',5'-phosphorofluoridate and its sulfur analogue via the phosphoroamidite route. AB - We describe the convenient synthesis of thymidine cyclic 3', 5' phosphorofluoridate 6, which is superior to that previously reported. Our procedure is based on a sequence of reactions utilizing 3 as the key substrate. Similar sequence of reaction leads to the sulfur analogues of 6 the thymidine cyclic 3',5'-phosphorofluoridothioate 7. PMID- 11200273 TI - Synthesis of non-nucleoside triphosphate analogues, a new type of substrates for terminal deoxynucleotidyl transferase. AB - A series of non-nucleoside triphosphate analogues were synthesized. In place of the nucleoside fragment, substituents bearing aromatic groups were introduced; the triphosphate component was replaced at alpha, beta, or gamma-positions by phosphonates. Alpha-[2-N-(9-Fluorenylmethoxycarbonyl)aminoethylphosphonyl] beta,gamma-difluoromethylenediphosphonate (IIc) revealed the best substrate properties toward terminal deoxynucleotidyl transferase. PMID- 11200274 TI - P-(alkyl)-nucleoside 5'-hydrogenphosphonates as depot forms of antiviral nucleotide analogues. AB - P-(Alkyl)esters of AZT 5'-hydrogenphosphonate were synthesized and their stabilities in the phosphate buffer and human serum were evaluated. The esters bearing residues of primary and secondary alcohols were degraded to give AZT, whereas those containing tertiary alkyl groups yielded AZT 5' hydrogenphosphonate. The corresponding derivatives of d2A and d4T showed the same properties. PMID- 11200275 TI - Probing the MVAI methyltransferase region that interacts with DNA: affinity labeling with the dialdehyde-containing DNA duplexes. AB - Affinity labeling of methyltransferase MvaI by DNA duplexes containing oxidized 2'-O-beta-D-ribofuranosylcytidine or 1-beta-D-galactopyranosyl)thymine residues was performed. Partial chemical hydrolysis of the covalently bound methylase in the conjugates with the dialdehyde-containing DNA allowed us to determine the amino acid region in the C terminus of methylase MvaI that interacts with DNA. PMID- 11200276 TI - Synthesis and RNAse L binding and activation of a 2-5A-(5')-DNA-(3')-PNA chimera, a novel potential antisense molecule. AB - Fully automated solid-phase synthesis gave access to a hybrid in which 5' phosphorylated-2'-5'-linked oligoadenylate (2-5A) is connected to the 5'-terminus of DNA which, in turn, is linked at the 3'-end to PNA [2-5A-(5')-DNA-(3')-PNA chimera]. This novel antisense molecule retains full RNase L activation potency while suffering only a slight reduction in binding affinity. PMID- 11200277 TI - New pyrimidine cyclonucleosides with hydrogenated aglycones: synthesis and X-ray structures. AB - Acid catalysed transformations of (6S)-6,5'-anhydro-6-hydroxy-1-(2',3'-O isopropylidene-beta-D-ribofuranosyl)hexahydropyrimidine-2-thione are studied. (6R)-6,2'-anhydro-6-hydroxy-1-(alpha-D-ribofuranosyl)hexahydropyrimidine-2-thione was formed as a thermodynamically stable product. Two intermediates, (6S)-6,5' anhydro-6-hydroxy-1-(beta-D-ribofuranosyl)hexahydropyrimidine-2-thione and 6 hydroxy-1-(D-ribosyl)hexahydropyrimidine-2-thione and products of cleavage of glycosidic bond were identified in the reaction mixtures. Results of X-ray structural determination of the synthesised nucleosides are presented. PMID- 11200278 TI - Synthesis and properties of O-beta-D-ribofuranosyl-(1"-2')-adenosine-5"-O phosphate and its derivatives. AB - The synthesis of O-beta-D-ribofuranosyl-(1"-2')-adenosine-5"-O-phosphate and its suitably protected derivative for oligonucleotide synthesis have been developed. PMID- 11200280 TI - Pyrophosphoryl derivatives of 1-(2-deoxy-3-O-phosphono-methyl-beta- and -alpha-D erythro-pentofuranosyl)thymine: synthesis and substrate properties towards some DNA polymerases. AB - The synthesis of 1-(2-deoxy-3-O-phosphonomethyl-beta-D erythropentofuranosyl)thymine (17) and its alpha-anomer 18 is described. Attempts to prepare 1-[2-deoxy-3-O-(pyrophosphoryl)phosphonomethyl-beta-D-erythro pentofuranosyl]thymine (19) by an activation of the respective phosphonate 17 with 1,1'-carbonyldiimidazole (Im2CO) resulted in the quantitative formation of the corresponding pyrophosphonate derivative 21 (Scheme 2). Activation of inorganic pyrophosphate with Im2CO followed by the condensation with the phosphonates 17 and 18 afforded the desired analogues of nucleoside triphosphate 19 (35%) and its alpha-anomer 20 (27%) along with the respective pyrophosphonate derivatives 21 (37%) and 24 (38%) (Scheme 3). It was found that compounds 19 and 20 display (i) no substrate properties toward calf thymus terminal deoxynucleotidyl transferase (TDT) and AMV reverse transcriptase, and (ii) moderate substrate activity with E. coli DNA polymerase I (Klenow fragment). PMID- 11200279 TI - Oligonucleotides containing 9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-adenine and -guanine: synthesis, hybridization and antisense properties. AB - Synthesis of 9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-adenine (7, ara-A2'F) and -guanine (12, ara-G2'F) was accomplished via the condensation of 2,6 dichloropurine (1) with 2-deoxy-2-fluoro-1,3,5-tri-O-benzoyl-alpha-D arabinofuranose (2) as a key chemical step. Condensation of silylated N6 benzoyladenine (6) with 2 gave, after deblocking and chromatographic separation, ara-A2'F (7) (14%), it's alpha-anomer 8 (14%) and N7-alpha-isomer 9 (25%). The PSEUROT analysis of N9-betaD-arabinosides 7 and 12 manifested slight preference for the S rotamer (64%) for the former, and an equal population of the N and S rotamers for the latter. The arabinosides 7 and 12 were used for the preparation of the respective phosphoamidite building blocks 13 and 14 for automated oligonucleotide synthesis. Four 15-mer oligonucleotides (ONs) complementary to the initiation codon region of firefly luciferase mRNA were prepared: unmodified 2'-deoxy-ON (AS 1) and containing (i) ara-A2'F instead of the only A (AS2), (ii) ara-G2'F vs. 3-G from the 5'-terminus (AS3), and (iii) both arabinosides at the same positions (AS4). All these ONs display practically the same (i) affinity to both complementary DNA and RNA, and (ii) ability to inhibit a luciferase gene expression in a cell-free transcription-translation system. PMID- 11200281 TI - Substituent--directed aralkylation and alkylation reactions of the tricyclic analogues of acyclovir and guanosine. AB - Aryl or tert-butyl substituent in the 6 position of 3,9-dihydro-3-[(2 hydroxyethoxy)methyl]-9-oxo-6-R-5H-imidazo[1,2-a]purine (6-R-TACV) 1 partly directs aralkylation reactions into unusual positions: N-4 to give 3 and C-7 to give N-5,7-disubstituted or N-4,7-disubstituted derivatives. In the case of alkylation the effect is limited to aryl substituent and position N-4. Replacement of acyclic moiety of 1 with a ribosyl one like in 7 prevents N-4 substitution. Cleavage of the third ring of 3b to give 3-benzylacyclovir 10 is an example of a new short route to 3-aralkyl-9-substituted guanines. PMID- 11200282 TI - A new strategy of discrimination of a point mutation by tandem of short oligonucleotides. AB - A new strategy based on the use of cooperative tandems of short oligonucleotide derivatives (TSOD) has been proposed to discriminate a "right" DNA target from a target containing a single nucleotide discrepancy. Modification of a DNA target by oligodeoxyribonucleotide reagents was used to characterize their interaction in the perfect and mismatched complexes. It is possible to detect any nucleotide changes in the binding sites of the target with the short oligonucleotide reagent. In the presence of flanking di-3',5'-N-(2-hydroxyethyl)phenazinium derivatives of short oligonucleotides (effectors) the tetranucleotide alkylating reagent modifies DNA target efficiently and site-specifically only in the perfect complex and practically does not modify it in the mismatched complex. It has been shown that TSOD is much more sensitive tool for the detection of a point mutation in DNA as compared to a longer oligonucleotides. PMID- 11200284 TI - Large-scale solid-phase preparation of 3'-unprotected trinucleotide phosphotriesters--precursors for synthesis of trinucleotide phosphoramidites. AB - The approach to large-scale solid-phase synthesis of 3'-unprotected trinucleotide phosphotriesters has been developed. The trinucleotides have been synthesized in 5 g scale by phosphotriester approach using CPG with pore size 70A. Total yield of target products was 75-90%. The molar extinctions of trinucleotides at various wave-lengths were calculated; the experimental UV-spectra of trinucleotides show a good agreement with theoretical ones. The trinucleotides synthesized were used for synthesis of trinucleotide phosphoramidites - synthons for generation of DNA/peptide libraries. PMID- 11200283 TI - Rapid routes of synthesis of oligonucleotide conjugates from non-protected oligonucleotides and ligands possessing different nucleophilic or electrophilic functional groups. AB - Optimized methods are described for post-synthetic conjugation of non-protected oligodeoxyribonucleotides to different ligands. Methods for the terminal functionalization of oligonucleotides by amino, sulfhydryl, thiophosphate or carboxyl groups using different chemical reactions and linkers in both organic and aqueous media are described and compared. Experimental conditions for subsequent coupling of ligands containing aliphatic and aromatic amines, aromatic alcohols, carboxylic, sulfhydryl, alkylating, aldehydic and other reactive nucleophilic and electrophilic groups to oligonucleotides were established, including covalent linkage to other oligonucleotides. PMID- 11200285 TI - S,X-acetals in nucleoside chemistry. III. Synthesis of 2'- and 3'-O-azidomethyl derivatives of ribonucleosides. AB - 2'- and 3'-O-azidomethyl derivatives of ribonucleosides were obtained by splitting the corresponding methylthiomethyl derivatives of ribonucleosides with bromine or SO2Cl2 followed by lithium azide treatment. PMID- 11200286 TI - Synthesis of N-labeled peptidyl AMP. AB - This paper deals with the synthesis of a new type of N-labeled peptidyl AMP, which would be used as a good substrate for analysis of the peptidyl transfer reaction on ribosome and for co-crystallization with ribosome. 4 (Dimethylamino)azobenzene-4'-sulfonyl (Dabsyl) was selected as the labeling group. (N-Dabsylglycyl)-L-leucyl AMP was synthesized from glycyl-L-leucine via a three-step procedure. PMID- 11200287 TI - Synthesis and structure activity relationships of 5-substituted-4'-thio-beta-D arabinofuranosylcytosines. AB - Four 5-substituted (chloro, fluoro, bromo, methyl) 1-(4-thio-beta-D arabinofuranosyl)cytosines and their alpha anomers were synthesized by a facile route in high yields. All of these nucleosides were evaluated for cytotoxicity against a panel of human tumor cell lines in vitro. Only 5-fluoro-1-(4-thio-beta D-arabinofuranosyl)cytosine was found to be highly cytotoxic in all the cell lines and was further evaluated in vivo. PMID- 11200288 TI - Inhibition of human immunodeficiency virus type-1 (HIV-1) replication by immunor (IM28), a new analog of dehydroepiandrosterone. AB - The inhibition of HIV-1 replication in vitro by Immunor 28 (IM28), an analog of dehydroepiandrosterone (DHEA), was monitored using the HIV-1 laboratory wild-type strain IIIB. Evaluation of the 50% inhibitory dose (IC50) revealed a decrease in HIV-1 replication giving an IC50 value around 22 microM. The toxicity of the drug has been determined also, in MT2 cells and PBMCs. 60 microM of IM28 provoked a 50% decrease in cell viability while DHEA caused the same decrease at 75 microM in MT2 cells. These values are 125 microM for IM28 in PBMCs and 135 microM for DHEA. Thus, DHEA is less toxic than IM28, but IM28 has a higher antiviral activity. PMID- 11200289 TI - Biographical sketch. Professor Alexander Krayevsky PhD, (1932-1999). PMID- 11200290 TI - Selected publications (1961-2000). Alexander Krayevsky. PMID- 11200291 TI - Atrial fibrillation occurring in a patient taking etanercept plus methotrexate for rheumatoid arthritis. AB - A 57-year-old man with nodular rheumatoid arthritis was started on a combination of etanercept and methotrexate. After treatment for five months on this therapy, he presented with new-onset atrial fibrillation. While this report is anecdotal, any new drug warrants intense monitoring for unexpected toxicities in the post marketing period. Etanercept is being tried in patients with congestive heart failure, where TNF-a seems to be increased. Further surveillance and caution are suggested in patients with known coronary artery disease or atrial dysrhythmia. PMID- 11200292 TI - Creating a physician Web site: Part 2. AB - An individual physician web site is a valuable augmentation to a professional practice. Enhancing patient care and increasing customer satisfaction are the most important goals of a physician web venue. Broadening your patient base, improving practice efficiencies, helping ensure corporate compliance, and decreasing liability exposure can also be accomplished by a well thought out and constructed site. Pages presenting information about the practice, the delineation of patient responsibilities, and evidence-based clinical content information will constitute the majority of the site. A user agreement and disclaimer page, feedback page, and corporate compliance page constitute the supplementary pages on the site. PMID- 11200293 TI - Domestic violence: a Resource Manual for Healthcare Providers for the State of Delaware. Part 3: Health Care Provider's Response. AB - The Medical Subcommittee of the Delaware Domestic Violence Coordinating Council (DVCC) has worked on and completed Domestic Violence: A Resource Manual for Healthcare Providers for the State of Delaware. It is both an educational tool and a handy resource for documentation and reference, with many examples of clinical guidelines, screening questions and checklists for safety screening. It is intended for all healthcare providers, not just physicians. The Delaware Medical Journal will be reprinting three very important chapters from this manual: Understanding Domestic Violence (October 2000), Legal issues (November 2000), and Health Care Provider's Response. PMID- 11200294 TI - What is health management research? PMID- 11200295 TI - A realistic theory of health sector management. The case for critical realism. AB - To date the practice of health sector management has not been sufficiently theorised. An adequate theory should be able to answer the pre-eminent critique of managerial rationality and ethics mounted by Alasdair MacIntyre in After Virtue and should also offer robust analytical and ethical resources to identify and engage with the social, political, economic and moral issues underlying health sector management. Critical realism with its ontology of generative mechanisms, agency-structure relationships, valorisation of activity and ideology critique offers such resources in an empirically orientated but adequately theorised realist framework. Rather than negate MacIntyre, critical realism incorporates and transcends his key arguments regarding the rationality and ethics of management. This article introduces the main elements of critical realism and clears a conceptual space for the cumulation of critical realist case studies and managerial craft knowledge. PMID- 11200296 TI - Who really wants health-care choice? AB - An experiment was conducted to examine the impact of patients' freedom to choose a physician and health locus of control on patient satisfaction. The experiment was set within the scenario of a patient suffering from a lengthy viral infection after visiting a health clinic for the first time. All constructs with corresponding measurements are discussed and their relationships with satisfaction are examined. Hypotheses are developed and tested for each relationship using pencil and paper scenarios of a patient's service encounter at a health clinic. A 2 x 2 full factorial between subjects experimental design was used with 99 subjects. Results of the experiment indicated different patterns of satisfaction among subjects based on measures of health locus of control (HLC). Individuals with an internal HLC were more satisfied with having a choice of a physician than not having a choice and were also more satisfied than external HLC individuals who had a choice. In contrast, individuals with an external HLC did not discriminate between having or not having the opportunity to choose a physician. PMID- 11200297 TI - Effective leadership within hospice and specialist palliative care units. AB - In this study the Repertory Grid interview technique was used to investigate constructs of leadership held by a group of male and female senior managers from within hospice and Specialist Palliative Care Units (SPCUs) in the UK. The themes that emerged were compared with those from existing research models of leadership. RESULTS: Men and women in these roles describe different constructs of effective leadership. The women's constructs that emerged were predominantly transformational, whilst the men's were predominantly transactional. Themes were also identified in this study, which differed from previous studied, i.e. those of political and environment awareness and the valuing of others' views regardless of their status. These themes do not feature highly in other research, and may be in response to the environment within which hospice and specialist palliative care functions. PMID- 11200298 TI - Renewing the model employer. Changing employment relations and "partnership" in the health and private sectors. AB - Drawing from original empirical data this paper compares the changing nature of employment relations in the health and private sectors. A key concern is to assess the extent to which the emergence of partnership-type arrangements between employers and trade unions lays the basis for the "renewal" of the traditional public sector concept of the model employer. Empirically, the paper draws on a survey of trade union representatives from 238 workplaces and a case study of a hospital trust. The data reveal that employment relations in the NHS are more collectivist when compared with the private sector. However, the development of partnership in the NHS is hamstrung by ongoing training and involvement gaps and widespread work intensification. PMID- 11200299 TI - The value of the facilities management function in the UK NHS community health care sector. AB - This paper stresses the importance of the strategic integration of the organisational facilities management function as being an essential prerequisite towards facilities and organisational effectiveness. The impact of both the strategic and operational facilities management function on community health-care facility users is also documented. The value of the facilities management function in terms of other health-care related organisational core deliverables is also observed. Mechanisms for general organisational facilities management improvement are identified and a number of facilities management performance measuring tools outlined. PMID- 11200300 TI - Patient perceptions of service quality. Combining the dimensions. AB - Empirically investigates, using a conjoint methodology, the importance weights given to the attributes of quality for acute care hospital services. The study shows that consumers evaluated the technical dimensions of nursing care, physician care, and outcome as more important than the accommodation functions of hospital care, and there are significant interactions among the technical dimensions. Both sets of dimensions were important and significant, but technical quality evaluations were not influenced by the perceived quality level of the affective attributes. The relative importance of these attributes were quite stable among various subgroups of past patients. PMID- 11200301 TI - Quality in health care. Medical or managerial? AB - Explores the notion that the introduction of total quality management (TQM) in the public health-care sector indicates a conceptual break with a tradition in which the authority to define and interpret the meaning of medical practice has been located solely within the medical profession. It also serves to shift the focus of medical practice away from its contextual and interactional character towards numerical representations and codification in monetary terms. Further, it is argued that the realization of management ideals in everyday practice is dependent more on the availability of pre-existing technologies and standard procedures than on the ingenuity of particular organizational and institutional actors. These arguments are illustrated with the reutilization for TQM purposes of "local incident reports" in a Swedish hospital organization. PMID- 11200302 TI - Basic estimate of needs for training in evidence-based medicine in Slovakia. AB - This study reports the findings of the first survey of the knowledge and needs for training in evidence based medicine (EBM) of health-care workers in Slovakia. This study was primarily qualitative and based on a triangular approach, which included: analysis of the situation in pre- and postgraduate education in Slovakia aimed at estimating needs in EBM and critical appraisal skills (CAS) training; analysis of questionnaires distributed in a sample of medical doctors and university educated public health workers undergoing postgraduate training; and focus group discussions. The findings revealed a real gap in knowledge in EBM and CAS in Slovakia and identified several areas as the focus for intervention. The results showed also some important behavioural and cultural aspects, including low individual responsibility for education; tendency to delegate responsibility to authorities (experts, top management, Ministry of Health); and persistence of the state paternalistic type of education. Concludes that managers planning to implement EBM in Slovakia should therefore consider a broader behavioural and cultural context for change, not just introduction of a training EBM module. PMID- 11200303 TI - Hospital human resource planning in Slovakia. AB - The study is an attempt to provide empirical evidence, in the context of acute hospital care, of the current human resource practices in the health sector of the Slovak Republic. Using a sample of 72 acute care hospitals the research explored the perceived functions, typical customers and priorities of hospital human resource departments, ownership of a workforce plan, and the relationships between ownership of a workforce plan and type of hospital, as well as the degree to which different human resource activities are given priority. Cross-tabulation procedure revealed statistically significant relationships between ownership of a workforce plan and the degree of priority given to having a quick, efficient and cost-effective recruitment and selection system and, not surprisingly, the degree of priority given to ensuring that the human resource department has a workforce plan. The study evidence also indicates that, although the human resource staff in hospitals seem to be aware of their role in assisting hospital management in decision making, the human resource function in the Slovak hospitals still rather resembles that of a personnel administration than that of an important strategic human resource activity. PMID- 11200304 TI - Testosterone: its role in development of prostate cancer and potential risk from use as hormone replacement therapy. AB - Evidence from studies in patients with prostate cancer of intermittent hormone therapy combined with results from rechallenge of hormone resistant patients with testosterone demonstrate that the majority of prostate cancers retain a similar degree of dependence on male sex hormone milieu as normal prostate cells. Yet there has so far been no conclusive evidence, despite 34 studies, that levels of circulating testosterone in individuals developing prostate cancer are higher than in controls. The aim of this article was to critically evaluate this evidence and seek clues to other mechanisms whereby sex hormones could influence the development of prostate cancer. Additionally, epidemiological data were examined to investigate the interplay between sex hormone levels and environmental factors to help understand the development of prostate cancer and identify a safe way to provide hormone replacement therapy (HRT). Three overviews provide similar evidence that there is no significant difference in mean testosterone levels between patients and controls. However in the most recent review of studies, though there was no difference in means between cases and controls, there was a significant risk (adjusted odds ratio 2.34) for individuals identified by comparing incidence of prostate cancer in men in the upper and lower quartile of testosterone level. This report, taken with epidemiological data demonstrating that prostate cancer risk is increased by early age of onset of sexual activity and multiple nonspecific sexually transmitted diseases (STDs), has led to the hypothesis that the link between sex hormones and prostate cancer is indirect. Those individuals with high testosterone levels were more at risk of acquisition of multiple nonspecific STDs. This promotes transformation of prostate cells and damage to Leydig cells in the testis leading to there being no difference in testosterone compared with controls by the time the tumour is diagnosed. Because of the observed relationship between testosterone and prostate cancer development there has been anxiety about marketing HRT for men. Two observations support the view that the prostate cancer risks from use of testosterone hormone replacement may not be as great as first feared. Firstly, prostate cancers arising in men with low serum testosterone levels are more malignant and frequently nonresponsive to hormones. Secondly, breast cancers diagnosed in women on HRT though increased in number are less malignant possibly because of enhanced sensitivity to hormone therapy, and the situation may prove to be analogous with prostate cancer and testosterone replacement. PMID- 11200305 TI - Choice and use of newer anticonvulsant drugs in older patients. AB - Epilepsy is common in the elderly. The incidence of epilepsy is age-dependent, with a peak during the first year of life and higher incidence in those older than 75 years. Cerebrovascular disease is a common cause of epilepsy in the elderly. Drug treatment of the elderly is a challenge because of pharmacokinetic changes with aging, including impaired drug protein binding or displacement of drug from protein binding sites, potentially causing drug toxicity as a result of increased free drug concentrations. With aging, hepatic mass and blood flow decline along with renal function. Established anticonvulsant drugs have adverse effects and drug interactions that can make treating the elderly difficult. Newly available anticonvulsants cause fewer drug-drug interactions and less toxicity. Gabapentin is not metabolised, is not bound to protein, and has a favourable adverse effect profile and thus may be useful in the treatment of elderly patients. Lamotrigine reduced seizures between 20 and 30% in trials. Dose response was between 300mg per day and 500mg per day. This drug was well tolerated in open-label trials. Rash occurred in younger patients. Oxcarbazepine is rapidly absorbed and is converted to a monohydroxy derivative. Use with hepatic enzyme-inducing drugs necessitates an increase in dose. This drug may be substituted for carbamazepine. Hyponatraemia has been reported and monitoring is suggested. Topiramate blocks voltage-dependent sustained repetitive firing and has an effect on the gamma-aminobutyric acid (GABA) receptors. It affects glutamate responses and inhibits carbonic anhydrase. Topiramate has a dose response pattern up to 400mg per day. Cognitive effects limits its use in some patients. Nephrolithiasis has occurred with this drug. Tiagabine blocks GABA transporter proteins. Clearance is rapid and metabolism complete. Hepatic dysfunction prolongs clearance. The use of tiagabine has not been reported in the elderly. Zonisamide is rapidly absorbed and protein binding is 50%. Plasma half life is 55 hours but is reduced to about 30 hours by hepatic enzyme-inducing drugs. Responder rate is 45%. Adverse effects include drowsiness, altered thinking and nephrolithiasis. Treatment of the elderly requires obligatory polypharmacy with potential drug interactions. Changes in body physiology alter absorption, binding, metabolism and elimination of drugs. Concomitant illness and sensitivity to drug effects narrow the therapeutic range and complicate pharmacokinetics in elderly patients. Newer anticonvulsant drugs have advantages that may outweigh risks and have therapeutic profiles that may aid in the treatment of this special population of patients. PMID- 11200306 TI - Glycaemic control and hormone replacement therapy: implications of the Postmenopausal Estrogen/Progestogen Intervention (PEPI) study. AB - Despite evidence that supports the beneficial effects of postmenopausal hormone replacement therapy (HRT), concerns remain about its possible adverse effects. However, entry into the postmenopausal state is associated with many characteristics of the insulin resistance syndrome, including increased cardiovascular morbidity and mortality, accretion of generalised and visceral adiposity and insulin resistance. Studies carried out in postmenopausal women have revealed that an increase in visceral obesity is associated with an increase in androgenicity that, in turn, is associated with type 2 (non-insulin-dependent) diabetes mellitus. Short term studies of HRT containing conjugated estrogens (CEE) and medroxyprogesterone (MPA) have shown prevention of the accretion of visceral fat. However, longer term studies using other techniques suggest that these effects may be evanescent. A few trials suggest that oral estrogen therapy reduces postmenopausal insulin resistance, as suggested by reductions in fasting insulin and glucose levels and an increase in glucose metabolism rates, whereas most studies do not show an adverse effect upon carbohydrate metabolism. MPA may decrease these beneficial effects. Transdermal estrogen is essentially neutral with regard to insulin sensitivity and oral estradiol (17beta-estradiol) may also be neutral or enhance sensitivity. Different progestogens vary in their effects upon carbohydrate metabolism. The Postmenopausal Estrogen/Progestogen Intervention (PEPI) Study was a prospective, 3-year, randomised trial in 875 women that compared placebo, unopposed CEE, CEE plus continuous MPA, CEE plus cyclical MPA, and CEE plus cyclical micronised progesterone. Fasting insulin and glucose levels decreased significantly by 16.1% and 0.122 mmol/L, respectively, in all drug treatment groups. However, after a 75g glucose load, glucose levels at 2 hours increased by 0.33 mmol/L in the active treatment groups without a corresponding increase in insulin levels. No beneficial effects on waist/hip ratio could be demonstrated. Data from the PEPI trial also suggested that the maximum benefit regarding carbohydrate metabolism was achieved in patients who were the most hyperglycaemic and hyperinsulinaemic at the start of therapy. It can be concluded, therefore, that HRT has few, if any, harmful effects on carbohydrate metabolism and that it may be of benefit in women in modifying the long term complications of the postmenopausal state. PMID- 11200309 TI - [Evolution and weight and body composition determination after therapy for pathological obesity for measuring compliance in (re)-education]. AB - Obesity, and its associated complications, is one of the most costly diseases in modern civilisations. Dieting alone rarely gives good long-term results. The effect of the combination of nutritional education and moderately intensive physical exercise on the evolution of weight and Body composition has been analysed by bio-impedancemetry over a one-year period. Patients could be divided into four groups: patients lost after the 3-week nutritional course, patients neither dieting nor exercising, patients dieting and patients both dieting and exercising. The results for the four groups were the following: undeterminably, 5% loss compared to initial weight (and nearly 10% compared to reported maximum weight). 10% loss and 15% loss over one year. In the last group, Body composition showed a relative increase in muscle mass, which explains the lack of a drop in basal metabolic rates seen in the diet-alone group. This maintained metabolic rate probably prevented patients from weight cycling (yo-yo phenomenon). This result can be compared to other life-style changing studies or pharmacological treatments (Orlistat, sibutramine) of obesity, which resulted in an approx. 10% weight reduction. PMID- 11200310 TI - [Sleep apnea syndromes and traffic accidents]. AB - The sleep apnea syndrome (SAS) is an independent and important risk factor of traffic accidents. The risk is further increased by cofactors such as alcohol intake or poor visibility driving conditions. It is still difficult to prospectively identify apneic patients at forseeable driving risk; previous accidents, reaction tests, steering simulation tests as different polysomnographic parametres appear to be the most promising markers. The initiation of nocturnal nasal continuous positive airway pressure treatment (nCPAP) normalizes patient's accident risk. Unfortunately there does not exist any accurate European nor national regulation dealing with issuing a driving licence for persons with sleep apnea disorder. PMID- 11200307 TI - Beneficial and detrimental effects of intensive glycaemic control, with emphasis on type 2 diabetes mellitus. AB - Diabetes mellitus is a major health problem in the world. Several clinical trials have shown that some of the major complications of diabetes mellitus can be partially prevented or delayed by intensive glycaemic control. However, there are benefits and risks in aiming for near normal blood glucose levels. Intensive glycaemic control delays the onset and progression of retinopathy, nephropathy and neuropathy. Epidemiological and observational studies have shown that cardiovascular events may be correlated with the severity and duration of diabetes mellitus, but major randomised trials have only shown weak and nonsignificant benefits of intensive glycaemic management in decreasing event rates. A modest improvement in lipid profile results from blood glucose control although, in the majority of cases, not enough to reach current targets. Detrimental effects of intensive glycaemic control include bodyweight gain and hypoglycaemia. Controversial issues in the management of patients with diabetes mellitus include the unproven increase in cardiovascular morbidity from sulphonylureas and hyperinsulinaemia, and the still unknown long term effects of newer oral antihyperglycaemic agents alone or in combination with traditional therapies (such as sulphonylureas and metformin). It is important to individualise management in setting glycaemic goals. Control of cardiovascular risk factors through blood pressure and lipid control and treatment with aspirin (acetylsalicylic acid) and ACE inhibitors have consistently shown benefits in the prevention of both macro- and microvascular complications in patients with diabetes mellitus; these measures deserve priority. PMID- 11200311 TI - [Ruptures of the anterior cruciate ligament (ACL) during growth]. AB - Tears of the anterior cruciate ligament (ACL) in skeletally immature patients with open physes are becoming more frequent. The two main variants of this lesion include tibial eminence fractures with an avulsion of the bony avulsions of the ACL on the tibia and midsubstance ligament injuries. The treatment of bony avulsions is generally accepted. In complete midsubstance tears conservative treatment is insufficient, resulting in multiple giving way episodes and meniscal lesions. Controversy exists regarding the surgical treatment of complete midsubstance ruptures. Especially in younger patients with wide open physes, the risk of a growth disturbance due to transphyseal drilling has not been completely evaluated. In patients approaching physeal closure intraarticular ACL replacement using an autogenous bone-patellar tendon-bone graft has been shown to yield good short-term to mid-term results. There is a growing concern regarding the long term outcome of ACL grafts with higher rerupture rates being suspected in children compared to adults. For these reasons more clinical and experimental data are needed in forthcoming studies. PMID- 11200308 TI - Topical dorzolamide 2%/timolol 0.5%: a review of its use in the treatment of open angle glaucoma. AB - The nonselective beta-blocker timolol and the carbonic anhydrase inhibitor dorzolamide both lower intraocular pressure (IOP). Timolol and dorzolamide have different mechanisms of action and their effects are additive when administered together. Therefore, the 2 drugs are frequently used concomitantly to treat patients with open-angle glaucoma who have not adequately responded to first-line therapy. A barrier to good compliance with concomitant therapy is the need to administer 5 or 6 drops of medication on 2 or 4 occasions during the day. Timolol 0.5% and dorzolamide 2.0% have therefore been combined in a single formulation, reducing the number of administrations required to 2 per day. Clinical trials in patients with glaucoma have demonstrated that dorzolamide 2%/timolol 0.5% (dorzolamide/timolol) is superior to monotherapy with the individual components. When dorzolamide/timolol administered twice daily was compared with concomitant treatment with dorzolamide 2% and timolol 0.5%, each administered twice daily for 90 days, both regimens resulted in marked lowering of trough IOP (measured just before the morning dose) compared with baseline (reduction in IOP = 4.2mm Hg). The effect of the 2 regimens on IOP at all time points, both before treatment and at peak effect (2 hours after treatment), were virtually indistinguishable. When the combined formulation was compared with a concomitant regimen that included dorzolamide 2% 3 times daily and timolol 0.5% twice daily the concomitant regimen was slightly more efficacious than the combined regimen at trough after 90 days: IOP was lowered by 3.6mm Hg in the combined group versus 4.1 mm Hg in the concomitant group. Dorzolamide/timolol has been compared with concomitant administration of timolol 0.5% and the IOP lowering miotic drug, pilocarpine 2.0%. This non-blind patient-preference study found that both regimens reduced IOP. However, the dorzolamide/timolol combination was preferred by the patients because of reduced frequency and severity of adverse effects and less frequent administration. Dorzolamide/timolol was well tolerated in clinical trials, the adverse effects reflected those of the individual components, and no additional tolerability issues were identified. However, the potential for timolol to cause cardiorespiratory effects must be considered when prescribing this combination. Furthermore, dorzolamide is a sulfonamide and can cause allergic reactions in those who are hypersensitive to this class of drug. CONCLUSIONS: Dorzolamide/timolol is a well tolerated and effective fixed combination for lowering IOP in the treatment of open-angle glaucoma and is likely to be useful in those patients who do not respond adequately to first-line monotherapy. Compared with concomitant therapy with the same 2 drugs the primary advantage is convenience, which may lead to improved compliance. Studies of compliance and comparisons with other currently available combination therapies would be useful to fully define the value of the formulation. Nonetheless, dorzolamide combined with timolol in a single applicator system will be a useful addition to the treatment options for glaucoma, a leading cause of preventable blindness. PMID- 11200312 TI - [History of aspirin in the Grand Duchy of Luxembourg]. PMID- 11200313 TI - [15 years of exercise for cardiac patient in the Grand Duchy of Luxembourg: balance sheet and perspectives]. PMID- 11200314 TI - From the private to the public sphere. The first generation of lady nurses in England. PMID- 11200315 TI - From the lower east side to the upper Galilee. The pioneering experiences of Sara Bodek Paltiel, 1909-1993. PMID- 11200317 TI - Nurses' residences: using the built environment as evidence. PMID- 11200316 TI - Florence Henderson. The art of open-drop ether. PMID- 11200318 TI - Passing on more than a blank disc. A task for nursing historians. PMID- 11200319 TI - "The steel cocoon". Tales of the nurses and patients of the iron lung, 1929-1955. PMID- 11200320 TI - "Barren of results?" The tuberculosis nurses' debate, 1908-1914. PMID- 11200321 TI - Blood work. Canadian nursing and blood transfusion, 1942-1990. AB - The extension of blood transfusion to civilian populations was contingent on the availability of a nursing workforce capable of taking on increasingly responsible roles. Nurses assumed a variety of roles as they incorporated blood work into patient care and, in the process, enabled, embodied, and engendered it as nurses' and women's work. Initially, the student workforce facilitated transfusion through roles that were congruent with nursing's domestic roots. Later, it constrained the expansion of blood work because of its perpetually novice nature. Delegation constituted one strategy by which a limited number of persons could become experienced and autonomous in a particular role. As long as the skill remained limited, nurses shared its associated power and status, which differentiated them within the work culture. A few women were able to shape blood work to their advantage, using their expertise either as job security or as a bargaining point to negotiate better working conditions. However, when the skill was routinized and dispersed among many nurses, it became dirty work. The examination of one specific technology that shifted from medicine into nursing contributes insights to current issues of expanded roles and delegated skills. Nurses need to question seriously what is gained and lost as they take on and let go of technologies. They need to consider what kinds of knowledge will be needed and how best to develop it. Finally, they need to reflect how changes might complicate care giving and nurses' work. PMID- 11200322 TI - Care of the maternal breast. Techniques and nurses' roles, 1900-1948. PMID- 11200323 TI - Ideology and self-interest. Nursing, medicine, and the elimination of the midwife. PMID- 11200324 TI - [Pharmacokinetic analysis of alpha- and beta-adrenoreceptors in the chick embryo amnion]. AB - Following a stimulation with acetylcholine, the beta-adrenergic agonists adrenaline (A), noradrenaline (NA), isoproterenol (Iso) and salbutamol (Sal) induced a concentration-dependent decrease in the tone and (or) rate of amnion contraction with EC50 ISO < NA << A < Sal. Metaprolol, a specific beta 1 antagonist, induced a rightward shift in the dose-response curves of Iso, NA and A, whereas beta-antagonist butoxamine was ineffective. pA2 values for beta antagonists were propranolol 8.3, metoprolol 7.0, butoxamine 5.6. EC50 values of alpha-adrenergic agonists form a sequence: clonidine < NA << methoxamine < phenylephrine. Specific alpha-antagonists yohimbine and idazoxan were found to antagonise competitively the effects of NA. The data obtained characterize the adrenergic receptors mediating stimulation of amniotic contractile activity as alpha 2-adrenergic receptors. Inhibition of contractile receptors in amnion is mainly mediated by beta 1-adrenergic receptor activation. PMID- 11200325 TI - [Effect of inhibitors of synthesis of dopamine and its antagonists on Hydra attenuata regeneration]. AB - Obvious inhibition of the hydra regeneration with no subsequent morphological abnormalities, was shown to occur when using alpha-methylthyrosine and 3 Jthyrosine. alpha-Methyldopa induced a slight inhibition but a considerable morphological change: ectopic tentacles, projections, bipolar forms in the gastric fragment. The apical and basal fragments did not suffer. The role of neurotransmitters in the hydra morphogenesis is discussed. PMID- 11200326 TI - [Non-dopaminergic neurons expressing dopamine synthesis enzymes: differentiation and functional importance]. AB - The study has evaluated in vivo, ex vivo and in vitro ontogenesis and functional significance of the arcuate nucleus neurons expressing either individual enzymes of dopamine synthesis, tyrosine hydroxylase or aromatic L-amino acid decarboxylase as well as both of them (dopaminergic neurons) in rats from the 17th embryonic day to adulthood. Monoenzymatic tyrosine hydroxylase-containing neurons were initially observed on the 18th embryonic day. On the 20-21 day, the monoenzymatic tyrosine hydroxylase- or aromatic L-amino acid decarboxylase expressing neurons comprised more than 99% of the whole neuron population expressing the dopamine-synthesizing enzymes. The dopamine production in the fetus arcuate nucleus was sufficient to provide an inhibitory control of prolactin secretion like in adults. The data suggest a possibility of the dopamine synthesis in the fetus arcuate nucleus by the monoenzymatic neurons containing either tyrosine hydroxylase or aromatic L-amino acid decarboxylase expressing neurons in co-operation. PMID- 11200327 TI - [Localization, kinetic parameters, and functions of cholinesterase of the starfish ampulla]. AB - The starfish amplullae cholinesterase was shown to represent acetylcholinesterase and enhance its activity along with increasing motility of the starfish. Bundles of muscle fibres containing cholinesterase were found in the ampullae. Cholinesterase was shown to be localized in the muscle cells and in collagen layer in vicinity of the muscle cells. The data obtained suggest participation of the starfish ampullae cholinesterase in non-synaptic cholinergic transmission between the radial nerve axons and the muscle fibre extension. Besides, the enzyme could take part in functional relationship between the muscle cells and the outer epithelial cells of the starfish ampullae. PMID- 11200328 TI - [Analysis of the functional role in behavior of the neuromediator receptor by antisense knockdown of its gene expression]. AB - Now available nucleotide sequences of neurotransmitter receptor genes enable to apply oligonucleotides targeted to mRNAs of these genes for highly selective inactivation of their expression (antisense-knockdown) and for function determination of single receptor subtype by this experimental approach. The antisense-knockdown may be of special importance in case of receptor families members of which are pharmacologically similar. Advantages of the antisense technology for investigation into the brain neurotransmitter receptor function in regulation of behaviour, are discussed. PMID- 11200329 TI - [Stress-limiting nitric oxide system]. AB - The work substantiates a concept of the nitric oxide (NO) system as a universal transmitter and controller of physiological functions and as a new stress limiting system. The NO system can be activated by a stress, restrict release and/or production of stress hormones, restrict the stress damage to the organism, enhance the organism's resistance against stress, can be activated in adaptation to repeated exposure to environmental factors. Some specifics of the NO system differing it from other stress-limiting systems, are discussed. PMID- 11200330 TI - [Effect of hydrocortisone on purine actions in the nerve-muscle preparation]. AB - Daily administration of hydrocortisone first increased and then decreased amplitude of multiquantal end-plate currents induced by motor nerve stimulation. The initial facilitating phase of the hormone action was accompanied by elimination of the ATP pre-synaptic effect. Later the inhibitory effect of the ATP becomes restored. The counteraction of the ATP effect was reproduced in the isolated muscle bathed in the saline with hydrocortisone which suggests a non genomic action of the hormone on pre-synaptic P2 receptor. The data obtained suggest that prevention of the ATP inhibitory action might be a component of a facilitating acute stress reaction. PMID- 11200331 TI - [Functions of neuromediators in plants]. AB - In plants, neurotransmitters play a major biological role in chemo-signaling, as regulating agents of growth and development, membrane permeability, etc. In the plant cells, there are also main elements of cholinergic and aminergic systems including the enzymes as well as functional analogues of cholino- and aminoreceptors. It is important that the systems should be taken into consideration in fertilizing and chemical interaction of the plant cells. Acetylcholine and cholinesterase were shown to be secreted in male sexual cells (the pollen). Depression of cholinesterase on the gene level correlates with male sterility. Preliminary treatment of a female gametophyte with antagonists of acetylcholine and histamine, prior to pollination, blocked the normal process of fertilizing. Cholinesterase was also found in secrets released from the pollen surface and pistil. PMID- 11200332 TI - [Urokinase does not effect the tissue factor mediated monocyte pro-coagulant activity]. AB - Both spontaneous and endotoxin-induced tissue factor expressions were not altered by exogenous urokinase. Inhibition of endogenous urokinase and plasmin did not affect the endotoxin-induced monocyte tissue factor's activity. PMID- 11200333 TI - [Pre- and postsynaptic effects of the calcium channel blocker verapamil in the nerve-muscle preparation]. AB - Verapamil did not change the amplitude of the miniature and multiquantal end plate currents, synchronicity of the transmitter release and repetitive firing at the motor nerve endings. Verapamil shortened the decay of multiquantal currents, the effect being enhanced after acetylcholinesterase inhibition. In muscles with inhibited acetylcholinesterase, verapamil promoted the depression of successive end-late currents in rhythmic nerve stimulation. The data suggest that in skeletal muscles verapamil-sensitive calcium channels do not take part in physiological transmitter release or in chemical potentiation of the secretion after treatment with potassium channels blocking agents. PMID- 11200334 TI - [NMDA-Receptors in the central nervous system of the honey bee with kynurenine deficiency]. AB - Effects of some drugs on the short-term memory were tested. In kynurenine deficit, mutant snow laranja manifested the same pharmacological profile and 10 to 100-fold enhancement of sensitivity of the NMDA receptors' different sites. The data obtained suggest that the gene controlling the key enzyme activity of the kynurenine pathway of tryptophan metabolism is involved in regulation of the CNS NMDA receptors' functional condition. The kynurenines may be classified as endogenous modulators of the NMDA receptor sensitivity. PMID- 11200335 TI - [Triglyceride lipase activity and fatty acid transport in physical endurance in rats adapted to the muscular activity]. AB - Aerobic training led to enhancement of lipase activity in type IIA type muscles. Still more obvious changes were found in rats trained to aerobic swimming with maximal intensity. In latter activity, a rise of the fatty acid-binding protein (FABP) was revealed in types I and IIA skeletal muscles. These adaptive changes led to enhancement of lipid metabolism. It was also shown that the FABP content decreased after physical exercise more obviously in the trained animals due, probably, to their substance turnover enhancement. PMID- 11200336 TI - [Decrease of the Ca(2+)-dependent K(+)-current by cyclic guanosine monophosphate does not depend on phosphorylation]. PMID- 11200337 TI - [I. P. Pavlov Physiological Society at the Russian Academy of Sciences]. PMID- 11200338 TI - [Neurochemical Research Society at the Russian Academy of Sciences]. PMID- 11200339 TI - [Gerontological Society at the Russian Academy of Sciences]. PMID- 11200340 TI - [International conference on 'Problems of physiology under extreme conditions']. PMID- 11200342 TI - Percutaneous management of chronic pancreatic duct strictures and external fistulas with long-term results. PMID- 11200343 TI - Noninvasive vascular laboratory for evaluation of peripheral arterial occlusive disease. Part III--Clinical applications: nonatherosclerotic lower extremity arterial conditions and upper extremity arterial disease. PMID- 11200344 TI - Translumbar embolization of type 2 endoleaks after endovascular repair of abdominal aortic aneurysms. PMID- 11200345 TI - Balloon tamponade: a novel technique for visualizing and catheterizing the common bile duct after partial transection. PMID- 11200346 TI - Re: temporary balloon occlusion in the internal iliac arteries for control of hemorrhage during cesarean hysterectomy in a patient with placenta previa and placenta increta. PMID- 11200347 TI - Early cerebral infarction after embolotherapy of a pulmonary arteriovenous malformation. PMID- 11200348 TI - Training standards for physicians performing uterine artery embolization for leiomyomata: consensus statement developed by the Task Force on Uterine Artery Embolization and the standards division of the Society of Cardiovascular & Interventional Radiology--August 2000. PMID- 11200349 TI - PTA versus Palmaz stent placement in femoropopliteal artery obstructions: a multicenter prospective randomized study. AB - PURPOSE: To evaluate if stent placement is superior to percutaneous transluminal angioplasty (PTA) in the treatment of chronic symptoms in short femoropopliteal arterial lesions. MATERIALS AND METHODS: One hundred fifty-four limbs in 141 patients who ranged in age from 39 to 87 years (mean age, 67 years) were randomized to PTA (n = 77) versus PTA followed by implantation of Palmaz stents (n = 77). Inclusion criteria were patients with intermittent claudication (n = 108, Society of Vascular Surgery/International Society of Cardiovascular Surgery [SVS-ISCVS] categories 1-3) or chronic critical limb ischemia (n = 46 with either ischemic rest pain [category 4] or minor tissue loss [category 5]), short stenosis or occlusion (lesion length < or = 5 cm), and at least one patent run off vessel at angiography. Follow-up included clinical assessment, measurement of ankle/ brachial index (ABI), color duplex ultrasound, and/or angiography at 6 or 12 months. Angiographic follow-up between 12 and 36 months was available in 46 limbs (29.9%). RESULTS: In the PTA group, initial technical success was achieved in 65 of 77 limbs (84%) versus 76 of 77 (99%) limbs in the stent group (chi2 value = 0.009). Overall, major complications occurred in 3.9% (n = 6); n = 4 in the PTA group compared to n = 2 in the stent group. There was no difference between groups of treatment: hemodynamic/clinical success at 1 and 2 years in the PTA group was 72% and 65% versus 77% and 65% in the stent group (Gehan P value = .26). The cumulative 1- and 2-year angiographic primary patency rates were 63% and 53%, respectively, for both groups. The secondary 1- and 2-year angiographic patency rates were 86% and 74% in the PTA group versus 79% and 73% in the stent group (P = .5). CONCLUSION: After stent placement, the primary success rate was significantly higher than after PTA. However, 1-year angiographic and clinical/hemodynamic success was not improved. PMID- 11200350 TI - Contrast media-induced nephrotoxicity: identification of patients at risk and algorithms for prevention. PMID- 11200351 TI - The Legs for Life screening for peripheral vascular disease: compliance with physician recommendations in moderate- and high-risk assessed patients. AB - PURPOSE: To determine compliance within a community with recommendations made by physicians during the 1999 Legs for Life National Screening for Peripheral Vascular Disease (PVD) and Leg Pain. MATERIALS AND METHODS: Patients were initially screened for PVD by completion of the Legs for Life risk factor questionnaire and determination of bilateral ankle/brachial indexes (ABIs). Each patient subsequently met with an interventional radiologist or vascular surgeon. Patients with normal ABIs (>1.0 bilaterally) or mildly abnormal ABI(s) (<1.0 but >0.90) were classified at no and low risk for PVD, respectively; patients with ABI(s) of 0.70-0.89 were classified at moderate risk for PVD; and patients with ABI(s) <0.69 were classified at high risk for PVD. Risk factors for PVD were assessed by the consulting physician and discussed with all patients. Recommendations were made for additional evaluation and/or follow-up care, if necessary. Seven months after screening, patients who were assessed at moderate and high risk for PVD were contacted by telephone to determine if they had pursued additional care or testing. RESULTS: A total of 205 patients were screened for PVD, 48 (23%) of whom were determined to be at moderate to high risk. Forty-four (92%) patients were available for follow-up. At 7 months after screening, 31 (70%) patients had received no further medical advice or treatment. Thirteen (30%) of these patients had completed a follow-up appointment, but only three with a physician specializing in peripheral vascular disease. None of the patients had clinical follow-up with an interventional radiologist. Five (11%) patients had undergone noninvasive Doppler evaluation and one (2%) had undergone diagnostic arteriography. No patient had undergone any form of percutaneous or surgical intervention. CONCLUSION: Patient compliance with physician recommendations after outpatient screening for PVD is low. The Legs for Life screening program could be considered successful in that it provides for patient education and the identification of moderate to high-risk patients. Physicians participating in this program may have to modify their approach to patient screening and follow-up if a concomitant goal is to deliver specialty care. PMID- 11200352 TI - Uterine artery embolization: reduced radiation with refined technique. AB - PURPOSE: To determine the estimated absorbed ovarian dose (EAOD) and absorbed skin dose (ASD) that occurs during uterine artery embolization (UAE) using pulsed fluoroscopy and a refined procedure protocol. MATERIALS AND METHODS: The absorbed dose was measured in 20 patients who underwent UAE procedures. Radiation was limited by using low frequency pulsed fluoroscopy, bilateral catheter technique with simultaneous injections for embolization as well as pre-and postembolization exposures and focus on limitation of magnified and oblique fluoroscopy. Lithium fluoride dosimeters were placed both in the posterior vaginal fornix and on the skin at the beam entrance site. The vaginal dose was used to approximate the EAOD. Fluoroscopy time and exposures were recorded. The mean values for all patients were calculated and compared to our previous results obtained with conventional fluoroscopy and to threshold doses for the induction of deterministic skin injury. RESULTS: Mean fluoroscopy time was 10.95 min. (range 6 21.3 min.) and the mean number of angiographic exposures was 20.9 (range 14-53). The mean EAOD was 9.5 cGy (range 2.21-23.21 cGy) and the mean ASD was 47.69 cGy (range 10.83-110.14 cGy). This compares to previous results with non-pulsed fluoroscopy of an EAOD of 22.34 cGy (range 4.25-65.08 cGy) and an ASD of 162.32 cGy (range 66.01-303.89 cGy) as well as threshold doses for induction of deterministic radiation injury to the skin (400-500 cGy). CONCLUSION: When pulsed fluoroscopy is used with emphasis on dose reduction techniques, the EAOD and ASD can be substantially reduced to less than 1/2 (P = .017) and 1/3 (P < .0001) when compared to UAE performed with nonpulsed fluoroscopy. These radiation reduction tools should therefore be applied whenever possible. PMID- 11200353 TI - Contrast-enhanced moving-table MR angiography: prospective comparison to catheter arteriography for treatment planning in peripheral arterial occlusive disease. AB - PURPOSE: Prospective comparison of contrast-enhanced moving-table magnetic resonance (MR) angiography to catheter arteriography in endovascular and surgical treatment planning in patients with peripheral arterial occlusive disease. MATERIALS AND METHODS: Thirteen patients scheduled for catheter arteriography for lower extremity arterial occlusive disease underwent contrast-enhanced moving table MR angiography immediately prior to arteriography. A treatment plan was determined by the vascular surgeon, based on MR angiography, who was blinded to the catheter arteriogram. The treatment plan determined by the MR angiogram was compared to the final treatment plan, which was based on the catheter arteriogram and intraluminal pressure measurements. RESULTS: Treatment plans based on MR angiography and catheter arteriography were identical in 10 of 13 patients (71%). For identifying lesions resulting in intervention, MR angiography had sensitivity of 100% and a positive predictive value of 92%. MR angiography had a treatment specific predictive value of 88% for each lesion identified, and 95% for lesions identified in patients evaluated for claudication. If treatment plans were based on MR angiography only, 46% of patients would have avoided catheter arteriography. CONCLUSION: Contrast-enhanced moving-table MR angiography may be an effective alternative to catheter arteriography in endovascular and surgical treatment planning in selected patients with peripheral arterial occlusive disease, but larger studies are necessary to confirm this. PMID- 11200354 TI - Classifying complications of interventional procedures: a survey of practicing radiologists. AB - PURPOSE: To determine the variability of radiologists' classification of complications from interventional procedures. MATERIALS AND METHODS: Fifteen test cases were selected from a database of morbidity and mortality cases that occurred in our department during the past 2 years. Ten cases were selected randomly, and five were chosen because of classification difficulties within our department. A survey with the case descriptions was presented to 145 SCVIR members via the World Wide Web and 48 were distributed to participants at a statewide angiography club meeting. Participants were asked to complete a short assessment of the their clinical background and to classify each case as "no complication," "minor complication," or "major complication." RESULTS: Thirty eight percent (74 of 193) of the surveys were completed. Seventy percent (52 of 74) of the respondents were affiliated with an academic program, 12% (nine of 74) were affiliated with private practice groups, and 18% (13 of 74) claimed both academic and private affiliation. The consensus rate in classifying the complications for the randomly selected cases varied from 50% to 95%, with a median of 69%, and the consensus rate in classifying the selected cases varied from 46% to 95%, with a median of 85%. The lowest consensus rates occurred when (i) a significant procedural event was followed by a normal outcome, (ii) when a procedure was aborted, and (iii) when a significant event occurred but did not prolong hospital stay. CONCLUSION: Current criteria for reporting complications are associated with moderate rates of disagreement among interventional radiologists. PMID- 11200355 TI - Transjugular liver biopsy with use of the shark jaw needle: diagnostic yield, complications, and cost-effectiveness. AB - PURPOSE: Obtaining transjugular liver biopsy specimens with use of single-use needle systems is expensive, whereas biopsy specimens obtained with use of reusable needle systems are frequently associated with inadequate core specimens. The authors report their experience with the reusable Cook Shark Jaw biopsy needle, including diagnostic yield, complications, and cost-effectiveness. MATERIALS AND METHODS: A retrospective audit was performed of a cohort of 134 patients who underwent 136 transjugular liver biopsies with use of a reusable 16 gauge Shark Jaw needle during a 30-month period. Specimen adequacy and complication rates were assessed and direct costs of expendable components calculated. Cost-effectiveness was expressed as cost-per-successful biopsy. RESULTS: Biopsies were technically successful in 126 of 136 (93%) patients, with diagnostic histologic core specimens obtained in 124 of 126 (98%) patients, for an overall success rate of 91%. Complications included capsular penetration in six (4.4%) patients, cardiac arrhythmia in two (1.5%) patients, and puncture site hematoma or bleeding in 10 (7.4%) patients. Three tract embolizations were performed for capsular penetration. No instances of subcapsular hematoma, hemoperitoneum, or sepsis occurred, and no deaths were attributed to the procedure. The cost of expendable components totaled $103 per biopsy, corresponding to a cost-effectiveness of $113/successful biopsy. CONCLUSION: Transjugular liver biopsy specimens obtained with use of the Shark Jaw needle have a diagnostic yield comparable to those obtained with use of single-use biopsy systems, at a substantially lower cost with no increase in serious complications. PMID- 11200356 TI - Nasolacrimal polyurethane stent placement for epiphora: technical long-term results. AB - PURPOSE: To assess technical problems related to implantation of a polyurethane stent to treat obstructive epiphora, and to assess the long-term patency of the nasolacrimal system. MATERIALS AND METHODS: Fluoroscopically guided placement of a polyurethane nasolacrimal stent was performed in 70 obstructed lacrimal systems of 62 patients with grade 3-4 obstructive epiphora. Follow-up was conducted for 1 20 months (average, 11.3 months). The obstruction was at the lacrimal sac in six systems, at the junction between the lacrimal sac and the nasolacrimal duct in 60 systems, and at the nasolacrimal duct in four systems. The cause of the obstruction was idiopathic in all cases but was probably residual to dacryocystitis. RESULTS: Of these 70 procedures, stent placement was technically successful in 61 systems (87%). On long-term follow-up, 41 (67.2%) stents remained in place, with resolution or clinical improvement, and 18 (29.5%) stents were removed (because of occlusion in 17 systems), with stent malpositioning in the duct in six cases. There were seven cases of malpositioning in all. Statistical analysis was performed to evaluate patency, compare patency in properly positioned stents and malpositioned stents, and establish the relationship between malpositioning and the need for irrigation to maintain stent patency. Of the total 70 stents originally placed, 41 (58.6%) were still in place and functional at long-term follow-up. At 1 year, 73% of properly positioned stents remained patent versus 0% of improperly positioned stents. Median stent patency in the former group was 20 months and was 1 month in the latter group (P = .00002). Eleven percent of properly positioned stents required irrigation versus 57% of incorrectly positioned stents (P = .01). CONCLUSION: After follow up for 1 year, recurrence of epiphora brought on by stent obstruction was 28%. Early stent blockage and the need for periodic irrigation may be indicative of malpositioning of the stent. PMID- 11200357 TI - Sclerotherapy with use of doxycycline after percutaneous drainage of postoperative lymphoceles. AB - PURPOSE: To assess the use of doxycycline as a sclerosing agent after percutaneous drainage of postoperative lymphoceles. MATERIALS AND METHODS: Symptomatic postoperative lymphoceles (n = 21) in 18 patients were treated by percutaneous tube drainage for an average of 10.8 days. Sclerosis was performed when the patient became asymptomatic, drainage had slowed to less than 30 mL/d and follow-up imaging (CT or US) showed either near complete or total resolution of the lymphocele. Doxycycline (500 mg) combined with 1% lidocaine (5 mL) was instilled into the cavity with use of a syringe after any remaining lymphocele fluid was removed through the tube. When possible, patients were instructed to perform a series of maneuvers for the next hour to distribute the sclerosing agent evenly throughout the cavity. After 1 hour, the sclerosing agent was aspirated from the cavity and the drainage tube was removed. Three patients with four lymphoceles underwent sclerotherapy immediately after percutaneous insertion of a drainage tube and aspiration of the lymphocele. No patients underwent previous sclerosis with any agent. RESULTS: Successful treatment of postoperative lymphoceles was achieved in 17 of 18 patients. Primary success was achieved in 17 of 21 lymphoceles treated. There were four lymphocele recurrences in three patients. Three of the four recurrences were successfully treated by means of repeated drainage and sclerotherapy. One recurrent lymphocele persisted after re treatment with 1 g of doxycycline. This patient underwent successful surgical repair. There were no complications related to doxycycline sclerosis. The mean duration of drainage for initial and recurrent lymphoceles was 10.8 days (range, 0-30 days). CONCLUSION: Sclerotherapy with use of doxycycline after percutaneous drainage is an easy, safe, inexpensive, and effective means of treating postoperative lymphoceles. PMID- 11200358 TI - Complete inhibition of intimal hyperplasia by perivascular delivery of paclitaxel in balloon-injured rat carotid arteries. AB - PURPOSE: To determine whether perivascular delivery of paclitaxel prevents luminal narrowing after balloon injury by inhibiting intimal hyperplasia. MATERIALS AND METHODS: Immediately after balloon injury of the entire left common carotid artery, three slow-release formulations of paclitaxel or control formulations without drug were applied around a distal segment of the artery. The noninjured right carotid arteries were evaluated as a control. The animals were maintained for 14 and 28 days (n = 5 in each group at each time interval). Histology, immunohistochemistry, and morphometric analysis were performed. RESULTS: Injured nontreated arteries exhibited a pronounced intimal hyperplasia (0.185 +/- 0.01 mm2 at 14 days and 0.189 +/- 0.01 mm2 at 28 days) and a marked reduction in luminal area (44% at 14 days and 43% at 28 days). Medial area and the number of medial cells increased by 44% and 45%, respectively, at 14 days, and by 22% and 37%, respectively, at 28 days. Injured arteries treated with perivascular paclitaxel did not show any intimal hyperplasia, and luminal area was increased in five of six groups and was unchanged in one group. These arteries had an increased medial area but they had fewer medial cells than noninjured arteries. Injured arteries treated with control implants without paclitaxel exhibited intimal hyperplasia and luminal narrowing. CONCLUSION: Perivascular slow release of paclitaxel totally inhibits intimal hyperplasia and prevents luminal narrowing after balloon injury. Because of its efficacy, perivascular paclitaxel represents a possible approach for prevention of restenosis in humans. PMID- 11200359 TI - The effects of a mechanical thrombolytic device on normal canine vein valves. AB - PURPOSE: To determine if the Arrow-Trerotola Percutaneous Thrombolytic Device (PTD) causes damage to normal vein valves. MATERIALS AND METHODS: Ten lateral saphenous veins in five dogs were studied with descending venography with use of a wedge balloon catheter positioned above 48 valves (demonstrating 51 valves) before and after five antegrade passes each with an over-the-wire (0.025-inch), 6.5-F, 9-mm-diameter PTD. Vein diameters were 3.2-11.4 mm (mean, 5.9 mm). Contrast matter was injected at incremental rates from 3 to 15 mL/min during continuous pressure monitoring. Imaging was performed with digital subtraction angiography at a rate of 1 frame/sec. The time to valve reflux was determined by noting the frame at which reflux was first seen through the valve. The time to reflux and pressure required to reflux were compared before and after the PTD passes. All vessels were explanted and evaluated histologically for presence or absence of endothelial loss, thrombus formation, inflammation, or valve degeneration. Four veins in two animals were studied with venography to determine the variability of the venographic method. These veins thrombosed during venography and therefore served as positive pathologic controls. In two animals, one vein was studied with venography and one was not studied to provide pathologic controls. RESULTS: With use of two physiologic tests of valve function, 77% of valves had minimal or no damage as assessed by valve competency and 80% had minimal or no damage as demonstrated by the change in the pressures the valve can withstand before reflux. Twenty-six of 51 valves (51%) had no difference or later reflux after PTD use. Thirteen (26%) refluxed 1 second earlier after PTD use and 12 (23%) refluxed > or =2 seconds earlier (six at 2, four at 3, and two at 4). Four of the six valves with more than a 2-second difference in reflux times were in valves with diameters less than 4.2 mm. All these vessels were smaller than 7 mm in diameter. Twenty-one of 48 valve levels (44%) had no difference or sustained higher pressures before reflux after PTD use. Seventeen (36%) had a pressure drop of <10 mm Hg; five (10%) had drops of 12 24 mm Hg; and five (10%) had drops of more than 40 mm Hg. There was a significant difference in endothelial loss, thrombus formation, and inflammation between experimental veins, the veins with thrombus, the venography controls, and the normal vein controls. There was significant difference only in terms of inflammation when the experimental group was compared to the thrombosis group. CONCLUSION: The antegrade use of the PTD across normal canine vein valves does not cause physiologically significant damage in valves 7 mm or larger in diameter in this animal model. PMID- 11200360 TI - Preclinical in vivo testing of the Arrow-Trerotola percutaneous thrombolytic device for venous thrombosis. AB - PURPOSE: To test the safety and efficacy of using the Arrow-Trerotola percutaneous thrombolytic device (PTD) for treating deep vein thrombosis (DVT) in an animal model. MATERIALS AND METHODS: An established canine model of iliocaval subacute thrombosis was used. Thrombosis was caused by balloon occlusion of the infrarenal inferior vena cava (IVC) for 7 (n = 12), 10 (n = 1), or 17 (n = 1) days. Treatment was performed with use of an 8-F, over-the-wire (0.035-inch) PTD with a 15-mm-diameter basket. The procedure was performed without IVC filtration. Two acute procedures were performed and 12 procedures were intended as survival procedures with 30-day follow-up. Pulmonary arteriography, blood gases, and pulmonary artery pressure measurement were performed before and after the procedure, and at follow-up. The animals were killed after the follow-up procedure and their IVC, iliac veins, and lungs were removed and examined histologically. Heparin was used intraprocedurally but thrombolytic agents were not used. Low-molecular-weight heparin was given daily after the procedure. RESULTS: Thrombolysis was completely (12 of 13) or partially (one of 13) successful in all animals in the 7- and 10-day groups, but was unsuccessful in the animal in the 17-day group (n = 1). Variable amounts of segmental and subsegmental pulmonary emboli were found in all animals with small increases in pulmonary artery pressure. Two animals died within 6 days of the procedure, possibly due to pulmonary emboli. At 30-day follow-up, IVC patency was preserved in 80% (eight of 10) of animals, but significant caval narrowing due to intimal hyperplasia was noted at follow-up. All pulmonary emboli had resolved angiographically at follow-up, but evidence of recanalized or resolving pulmonary thromboemboli was found in seven of the 12 surviving animals. No acute vascular injury (eg, perforation) occurred. CONCLUSION: The modified PTD used in this study is effective in treating subacute (<7 days old) venous thrombosis, but temporary filtration will probably be necessary to keep pulmonary emboli to a minimum during the procedure. The 30-day patency is encouraging. The results in this animal model indicate that the Arrow-Trerotola PTD may be useful in the percutaneous treatment of DVT in humans. PMID- 11200361 TI - Bothrops asper snake venom and its metalloproteinase BaP-1 activate the complement system. Role in leucocyte recruitment. AB - The venom of the snake Bothrops asper, the most important poisonous snake in Central America, evokes an inflammatory response, the mechanisms of which are not well characterized. The objectives of this study were to investigate whether B. asper venom and its purified toxins--phospholipases and metalloproteinase- activate the complement system and the contribution of the effect on leucocyte recruitment. In vitro chemotaxis assays were performed using Boyden's chamber model to investigate the ability of serum incubated with venom and its purified toxins to induce neutrophil migration. The complement consumption by the venom was evaluated using an in vitro haemolytic assay. The importance of complement activation by the venom on neutrophil migration was investigated in vivo by injecting the venom into the peritoneal cavity of C5-deficient mice. Data obtained demonstrated that serum incubated with crude venom and its purified metalloproteinase BaP-1 are able to induce rat neutrophil chemotaxis, probably mediated by agent(s) derived from the complement system. This hypothesis was corroborated by the capacity of the venom to activate this system in vitro. The involvement of C5a in neutrophil chemotaxis induced by venom-activated serum was demonstrated by abolishing migration when neutrophils were pre-incubated with antirat C5a receptor antibody. The relevance of the complement system in in vivo leucocyte mobilization was further demonstrated by the drastic decrease of this response in C5-deficient mice. Pre-incubation of serum with the soluble human recombinant complement receptor type 1 (sCR 1) did not prevent the response induced by the venom, but abolished the migration evoked by metalloproteinase activated serum. These data show the role of the complement system in bothropic envenomation and the participation of metalloproteinase in the effect. Also, they suggest that the venom may contain other component(s) which can cause direct activation of C5a. PMID- 11200362 TI - Effect of ricinoleic acid in acute and subchronic experimental models of inflammation. AB - Observational studies indicate that topical application of ricinoleic acid (RA), the main component of castor oil, exerts remarkable analgesic and anti inflammatory effects. Pharmacological characterization has shown similarities between the effects of RA and those of capsaicin, suggesting a potential interaction of this drug on sensory neuropeptide-mediated neurogenic inflammation. The aim of this study was to assess RA anti-inflammatory activities in comparison with capsaicin in several models of acute and subchronic inflammation. The acute inflammation was induced by intradermal injection of carrageenan in the mouse or by histamine in the guinea-pig eyelid. In either experiment, the extent of the oedema thickness was measured. Subchronic oedema was induced by complete Freund's adjuvant injection in the ventral right paw of mice. Tissue substance P (SP) was measured in the carrageenan experiments by radioimmunoassay (RIA). It was found that the acute topical application of RA (0.9 mg/mouse) or capsaicin (0.09 mg/mouse) significantly increased the mouse paw oedema induced by carrageenan, while an 8-day repeated topical treatment with the same doses of both compounds resulted in a marked inhibition of carrageenan induced paw oedema matched by a reduction in SP tissue levels. Similar effects were found against histamine-induced eyelid oedema in guinea-pigs after acute or repeated application of RA or capsaicin. RA and capsaicin given for 1-3 weeks reduced the established oedema induced by Freund's adjuvant, a subchronic model of inflammation, particularly if given by the intradermal route. Either in mouse paw or in guinea-pig eyelid, capsaicin but not RA by itself produced a slight hyperemia and activation of a behavioural response (e.g. scratching of the eyelids). On the basis of the present results, RA may be seen as a new capsaicin like, non-pungent anti-inflammatory agent suitable for peripheral application. PMID- 11200364 TI - Permeability characteristics of human endothelial monolayers seeded on different extracellular matrix proteins. AB - OBJECTIVE: To investigate whether endothelial monolayer permeability changes induced by inflammatory mediators are affected by the extracellular matrix protein used for cell seeding. METHODS: Human umbilical venular endothelial cells (HUVEC) were grown to confluent monolayers on membranes coated with either collagen, fibronectin or gelatin. The permeability to albumin and dextran was then assessed, both under normal conditions and after treatment with tumor necrosis factor-alpha (TNF-alpha) and bacterial lipopolysaccharide (LPS). RESULTS: With any of the three protein coatings, tight junctions were formed all over the monolayers. The permeability of the coated membranes to albumin and dextran was reduced strongly by confluent monolayers; the relative reduction was similar for the three matrix proteins used. Pre-incubation of the monolayers with either TNF-alpha or LPS increased permeability dose dependently. However, the relative increase due to either treatment was independent of the protein used for membrane coating. CONCLUSION: The extracellular matrix protein used for initial seeding of endothelial cultures plays a minor role in determining the permeability changes induced in HUVEC monolayers by inflammatory mediators. PMID- 11200365 TI - Effect of cyclosporin-A on the blood--retinal barrier permeability in streptozotocin-induced diabetes. AB - BACKGROUND: Our previous results showed that in retinas from streptozotocin (STZ) induced diabetic rats there is an increased level of interleukin-1beta (IL 1beta). This cytokine may be involved in the expression of the inducible isoform of the nitric oxide synthase (iNOS), with consequent synthesis of large amounts of NO and blood-retinal barrier (BRB) breakdown. AIMS: The aim of this work was to examine whether the administration of cyclosporin-A (Cs-A) to STZ-induced diabetic rats inhibits the synthesis of IL-1beta and the expression of the inducible proteins, iNOS and cyclo-oxygenase-2 (COX-2) in retinal cells, and whether the activity of these proteins contribute to BRB breakdown. METHODS: The level of IL-1beta was evaluated by ELISA and the NO production by L-[3H] citrulline formation. Expression of iNOS and COX-2 proteins was determined by two methods, western blot and immunohistochemistry. The permeability of the BRB was assessed by quantification of the vitreous protein. RESULTS AND DISCUSSION: Our results indicated that the levels of IL-1beta and NO in retinas from Cs-A-treated diabetic rats are significantly reduced, as compared to that in non-treated diabetic rats. The treatment of diabetic rats with Cs-A also significantly inhibited the expression of the inducible proteins, iNOS and COX-2. The evaluation of the vitreous protein content revealed that Cs-A also reduces the BRB permeability. Taken together, these results suggest that the increased production of the inflammatory mediators, IL-1beta and NO, in diabetes may affect the BRB permeability and therefore contribute to the development of diabetic retinopathy. PMID- 11200366 TI - Spread of Staphylococcus aureus in hospitals: causes and prevention. AB - Methicillin-resistant Staphylococcus aureus (MRSA) has become a major nosocomial pathogen in many hospitals worldwide. Even more alarming, MRSA strains that are vancomycin intermediate-susceptible are isolated with increasing frequency, making therapy for staphylococcal infections even more difficult and prevention more important than ever. Spread of S. aureus in hospitals and infection control measures are reviewed. The major sources of S. aureus in hospitals are septic lesions and carriage sites of patients and personnel. Carriage often precedes infection. The anterior nares are the most consistent carriage site, followed by the perineal area. Skin contamination and aerial dissemination vary markedly between carriers and are most pronounced for combined nasal and perineal carriers. The principal mode of transmission is via transiently contaminated hands of hospital personnel. Airborne transmission seems important in the acquisition of nasal carriage. Infection control strategies include screening and isolation of newly admitted patients suspected of carrying MRSA or S. aureus with intermediate resistance to vancomycin, implementation of an infection control program to prevent transmission of resistant strains between patients and hospital personnel, and institution of a proper antibiotic policy to minimize antibiotic resistance development. MRSA carriers should be treated with intranasal antibiotics, e.g. mupirocin, and skin disinfectants to eliminate carriage. Education of hospital personnel is essential. Improved knowledge about the best ways to ensure favourable infection control practices is needed. Active intervention against the spread of MRSA is important. PMID- 11200363 TI - Plasma cytokine response in mice with bacterial infection. AB - BACKGROUND: Exposure to microorganisms elicts the production of cytokines. These soluble factors enhance several innate immune functions and regulate the ensuing specific immune response aimed at limiting the spread of infection. AIM: This study was undertaken to quantify the plasma levels of pro-inflammatory cytokines during the course of primary Listeria monocytogenes and Campylobacter jejuni infection. Using an in vivo infection the relationship between endogenous cytokines and the bacterial number in the liver of infected animals was examined. METHODS: C57BL/6 mice were infected by the intraperitoneal route. At different time points we determined the number of colony-forming units of bacteria in the liver of infected animals and paralled these with the plasma levels of interferon gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL 6) measured by enzyme immunoassays. RESULTS: L. monocytogenes infection lasted 10 11 days. IFN-gamma production occurred in the early phase but was more pronounced after day 4, following the appearance of specific immunity. The duration of experimental campylobacteriosis was 15 days. Early IFN-gamma production was not significant but a progressive rise of this cytokine in plasma was seen during the second week post infection. Mice produced measurable amounts of plasma TNF-alpha immediately after being given viable L. monocytogenes, peaking on day 2-3 when the greatest number of bacteria was present in the examined organs. During C. jejuni infection plasma TNF-alpha was produced in a similar manner, but the highest concentrations were found a few days later than in listeriosis, in correlation with the different course of campylobacteriosis. The quantity of IL-6 increased and decreased in concordance with clearance of L monocytogenes and the clinical status of the animals. C. jejuni did not promote the induction of this cytokine. This is to some extent an unusual finding. With respect to the role of IL-6 in Th2 responses and antibody production, the appearance of this cytokine in campylobacteriosis was more expected. DISCUSSION: During systemic bacterial infection, a network of pro-inflammatory cytokines is activated and blood levels of these cytokines are elevated, albeit inconsistently, with large individual variations and depending on microbial characteristics and structure. PMID- 11200367 TI - Decrease in immune activation in HIV-infected patients treated with highly active antiretroviral therapy correlates with the function of hematopoietic progenitor cells and the number of naive CD4+ cells. AB - This study was conducted to determine the impact of immune activation, cytokine production and apoptosis on the naive CD4+ cell count and the function of hematopoietic progenitor cells during the initial phase of highly active antiretroviral therapy (HAART). Blood samples from 11 HIV-infected patients were collected prior to HAART and after 4 and 12 weeks of therapy. Flow cytometry was used to determine the naive CD4+ count and activated T cells. The cloning efficiency of progenitor cells was determined using a colony-forming cells assay. Finally, apoptosis and cytokine production were determined. During the study period, the naive CD4+ count and the cloning efficiency increased significantly. Immune activation was found in HIV-infected patients and decreased during HAART. The level of immune activation correlated negatively with both the naive CD4+ count and the function of progenitor cells. A negative correlation was found between apoptosis and the naive CD4+ count. Alterations in cytokine production during HAART or correlation between cytokine production and the naive CD4+ count or the cloning efficiency of progenitor cells were not detected. In conclusion, immune activation in HIV-infected patients treated with HAART is inversely correlated with the function of progenitor cells and the naive CD4+ count. PMID- 11200368 TI - A case of Q fever acquired in Sweden and isolation of the probable ethiological agent, Coxiella burnetii from an indigenous source. AB - Serologically verified indigenous Q fever is described in a 52-y-old male, who presented with persistent fever, muscle and joint pain, headache and non-purulent cough. Institution of doxycycline resulted in prompt recovery. Coxiella burnetii was isolated from mouldy hay in a barn. The strain differs from previously isolated ones in Sweden. PMID- 11200369 TI - Invasive group A streptococcal infections in Sweden in 1994 and 1995: epidemiology and clinical spectrum. AB - A nationwide study of invasive group A streptococcal (GAS) infections in Sweden during 1994-1995 was carried out. All Swedish microbiological laboratories were asked to report isolates of GAS from normally sterile sites. During the study period they were also asked to send their isolates for T typing. Questionnaires were sent to the physicians in charge of each patient. The incidence, serotype, clinical presentation, symptoms and outcome were recorded. Clinical data were obtained for 468 of 556 patients with GAS bacteraemia. The lethality rate was 16%, but was much higher (37%) in the 113 patients who developed streptococcal toxic shock syndrome (STSS). Streptococci of serotype T1 dominated during the study period and were linked to the increase in invasive GAS infections. They also carried an increased risk of causing STSS. Invasive streptococcal disease with STSS most often has an unknown primary focus or is associated with soft tissue infections. Invasive streptococcal disease not associated with STSS most often has a skin infection as portal of entry or else an unknown focus. PMID- 11200370 TI - Increased incidence of bacteraemia due to viridans streptococci in an unselected population of patients with acute myeloid leukaemia. AB - The aetiology, clinical characteristics and outcome of bacteraemia in patients with acute myeloid leukaemia were studied. All positive blood cultures collected at a haematological ward during 2 7-y periods were evaluated. Altogether, 274 episodes of bacteraemia in 152 patients were recorded, 80 episodes during 1980-86 and 194 during 1990-96. During the 2 periods, trimethoprim-sulfamethoxazol in combination with amikacin was the first-line empirical therapy in patients with neutropaenia and fever. In 1990, antimicrobial prophylaxis with ciprofloxacin and fluconazole was introduced. The incidence of bacteraemia due to viridans streptococci or coagulase-negative staphylococci increased from the first period to the second, whereas the incidence of Enterobacteriaceae decreased. In granulocytopaenic patients during 1990-96, viridans streptococci accounted for 21% of the isolates and in patients treated prophylactically with fluoroquinolone, viridans streptococci accounted for 31%. All viridans streptococci were sensitive to penicillin. At the time of the positive blood cultures, the patients of the second period were granulocytopaenic in 83% of the episodes. The mortality related to septicaemia during the later period was 13% and only 1 of 33 (3%) of the patients with viridans streptococci died. Eight patients (9%) died in relation to septicaemia following curative antileukaemic therapy. PMID- 11200371 TI - Antimicrobial susceptibility patterns of Streptococcus agalactiae in a German university hospital. AB - Group B streptococci (GBS) are the major cause of neonatal sepsis and meningitis. GBS infection in neonates is usually treated with a combination of penicillin and gentamicin. According to consensus guidelines, pregnant women at risk receive intrapartum prophylaxis with either ampicillin or penicillin or, in case of allergy, with erythromycin or clindamycin. We investigated the susceptibility patterns of 190 GBS strains from neonates isolated from 1993-1999 and 150 GBS strains collected from adult women in 1997 and 1999. All isolates were susceptible to penicillin, ampicillin and cefotaxime. Erythromycin resistance among all isolates from neonates and from adult women in 1997 was 4.7% and 6%, respectively. In contrast, 12% of the isolates from adult women in 1999 were resistant to erythromycin and 7% were resistant to clindamycin. These findings show an increasing macrolide resistance in recent GBS strains and indicate the need for further surveillance. PMID- 11200373 TI - Fusidic acid disk diffusion testing of clostridium difficile can be calibrated using single-strain regression analysis. AB - Single-strain regression analysis (SRA) was employed to calibrate the disk diffusion antibiotic susceptibility test for fusidic acid and Clostridium difficile. MIC determinations of 40 clinical isolates of C. difficile were performed with the E-test. The disk diffusion test was standardized according to the Swedish Reference Group for Antibiotics (SRGA). Disks used for SRA contained 1.5, 5, 15, 50 and 150 microg fusidic acid and the routine disk contained 50 microg fusidic acid. A control strain, ATCC 9689, was also tested. SRA constants A and B of the regression lines were calculated. This permitted the determination of zone breakpoints for C. difficile. When applying the pharmacological MIC S and R limits set by SRGA to the E-test results I strain of C. difficile was interpreted as resistant. Zone breakpoints corresponding to the pharmacological MIC limits and calculated using the mean SRA constants for the 40 clinical isolates lead to all strains being interpreted as susceptible. SRA calculations enable laboratories to set up calibrated disk tests with species-related and laboratory-specific interpretations. PMID- 11200372 TI - Impact on human intestinal microflora of an Enterococcus faecium probiotic and vancomycin. AB - The aims of this study were to evaluate the impact of a fermented milk product containing viable Enterococcus faecium on human intestinal microflora and to evaluate any risk of development of vancomycin-resistant enterococci (VRE). Twenty Danish and 20 Swedish healthy volunteers were given 150 ml of the fermented milk product once daily, equivalent to a daily dose of 4.5 x 10(9) to 7.5 x 10(9) CFU E. faecium, for 10 d. Half of the volunteers also received 125 mg vancomycin orally q.i.d. for 10 d. Faecal samples were collected on day 0 before intake, on day 10 directly after end of intake and on day 31, 3 weeks after the end of the experiment. There was a significant increase in the total number of enterococci on day 10 (p < 0.01) in the group receiving only the E. faecium supplement, but 3 weeks later the level was as before intake. In the vancomycin group, the total number of enterococci was reduced on day 10 (p < 0.01) but had increased on day 31 (p < 0.01) in relation to day 0. In none of the Swedish and 4 of the Danish volunteers, VRE were sporadically detected, but without relation to intake of the probiotic or vancomycin. In healthy young Danish individuals the VRE carrier rate tended to be higher than previously found. PMID- 11200374 TI - Molecular epidemiology survey of toxinogenic Clostridium perfringens strain types by multiplex PCR. AB - Toxin genotypes of 95 C. perfringens strains collected within a 45-year period were analysed by a multiplex PCR. A set of primers designed for 4 different genes encoding the alpha, beta, epsilon, and iota toxins was used in a single reaction with a sensitivity of gene detection of 200 fg for DNA extracted from pure culture. Most of the strains (97%) conformed to the A biotype, and the remaining to the C or E biotypes. For biotype determination, seroneutralization of lethality in mice was performed by intravenous injection. Toxin phenotype and genotype profile were concordant in 94% of strains. Our results documented the presence of rare toxin genotypes of C. perfringens in a Polish geographical region and indicated the suitability of multiplex PCR as a method supplementing classical techniques and providing better insight into the prevalence of toxinogenic C. perfringens strains. PMID- 11200375 TI - Synergy of Bacteroides fragilis and Escherichia coli in the induction of KC gene expression in mouse peritoneal tissues. AB - B. fragilis induces cytokine expression, which can serve as a host signal leading to inflammatory reaction and abscess formation in the peritoneal cavity. We assessed the hypothesis that enteric bacteria may alter the B. fragilis-induced expression of KC genes in mouse peritoneal tissues (MPT). After C57BL/6 mice were inoculated with abscess-forming mixture containing B. fragilis in the presence or absence of E. coli, RNA was extracted from MPT. Expression of KC mRNA was quantified using reverse-transcription polymerase chain reaction and standard RNA. KC and TNFalpha proteins were measured by enzyme-linked immunosorbent assay. KC mRNA in MPT was upregulated following inoculation of B. fragilis and this was paralleled by increased KC protein secretion. When the mice were co-infected with E. coli and B. fragilis intraperitoneally, there was a synergistic increase in the expression of KC of MPT. Co-infection with L. acidophilus and B. fragilis downregulated KC mRNA expression, but co-infection with E. faecalis and B. fragilis synergistically increased KC expression in the infected MPT. Inhibition of TNFalpha production could downregulate KC expression in mixed infected MPT. These results suggest that enteric bacteria may significantly affect the KC signal produced by the host peritoneal cavity in response to B. fragilis infection. PMID- 11200376 TI - Clinical implications of stenotrophomonas maltophilia resistant to trimethoprim sulfamethoxazole: a study of 69 patients at 2 university hospitals. AB - We conducted a retrospective case study at 2 tertiary care centers to determine the clinical implications of trimethoprim-sulfamethoxazole resistant Stenotrophomonas maltophilia (TSRSM). Of 69 reviewed cases (mean age, 57 y; male gender, 70%), 40 (58%) were classified as infections associated with TSRSM (respiratory tract, 14; soft tissue, 11; bloodstream, 8; other sites, 7). Severe underlying comorbidities (86%) and previous antibiotic exposure (99%) were common. Cefotetan (susceptibility, 55%), chloramphenicol (49%) and ticarcillin clavulanate (45%) showed the highest in vitro activity against TSRSM, but were seldom used for therapy (7%). Among the 40 infected cases, 8 developed sepsis disorders and 8 died. Only 1 death could be directly attributed to autopsy-proven TSRSM infection (pneumonia). McCabe score (p = 0.03) and organ dysfunction (p = 0.006) were associated with an increased risk of death in infected patients; exposure to appropriate therapy tended to be protective against death (p = 0.08). 22 infected patients were treated medically; an additional procedure was necessary to clear the infection in 18 cases (surgery, 13; catheter removal, 5). Isolation precautions were rarely exercised, even in the presence of panresistant isolates. In summary, TSRSM-related infections occurred in severely ill patients with extensive exposure to the health-care system, and often required invasive procedures for cure. Infections were directly associated with severe morbidity, and tended to have an indirect rather than a direct impact on mortality. PMID- 11200377 TI - Evaluation of 120 mycobacterial strains isolated from clinical specimens to the species level by polymerase chain reaction-restriction enzyme analysis. AB - In this study, a total of 120 mycobacterial strains isolated from clinical specimens in Hacettepe University Hospital Clinical Pathology Laboratories were evaluated by polymerase chain reaction-restriction enzyme analysis (PRA), which analyses the common mycobacterial heat shock protein gene (hsp65). 95 of 120 strains (79.1%) were identified as Mycobacterium tuberculosis and 25 (20.8%) were identified as non-tuberculous mycobacteria (NTM). M. gordonae I and IV were the most common NTM species (3.3% each) followed by M. chelonae (2.5%). Other NTM species isolated were M. gordonae III, M. avium, M. peregrinum (1.6%), M. fortuitum, M. flavescens, M. malmoense and M. mucogenicum (0.8%). Four isolates had PRA patterns that did not match any patterns previously described. The patients who had NTM had underlying diseases; the most frequent clinical diagnosis among these was chronic obstructive pulmonary disease (COPD) and chronic renal failure. AIDS and pulmonary carcinoma were the other underlying diseases detected. PMID- 11200378 TI - IS6110-RFLP and spoligotyping of Mycobacterium tuberculosis isolates in Iran. AB - To evaluate and compare the usefulness of IS6110-restriction fragment length polymorphism (RFLP) and spoligotyping in the epidemiology of tuberculosis in Iran, Mycobacterium tuberculosis complex strains, isolated in 2 different areas of Iran, were subjected to RFLP and spoligotyping. The average number of IS6110 copies per strain was 11 and ranged from 5 to 18 among the M. tuberculosis strains. In total, among the 62 isolates, 56 different patterns were observed. 50 strains had unique RFLP patterns (89%) and 12 (11%) revealed patterns that were found among at least 1 other isolate. Spoligotyping of 97 isolates resulted in 42 different patterns, of which 72% were found in 15 clusters. 14 (29%) out of 48 investigated isolates were resistant to 1 or more antituberculosis drugs and 57% of the resistant isolates were isolated from Afghan immigrants. Ten percent of the isolates represented the Beijing genotype, including 4 of the 14 (36%) resistant strains. Three of these resistant Beijing strains were isolated from Afghan patients. IS6110-RFLP typing could be useful for studying the epidemiology of tuberculosis in Iran. IS6110 patterns were polymorphic and the average IS6110 copy number was high. PMID- 11200379 TI - Influence of pH and concentration on the postantifungal effect and on the effects of sub-MIC concentrations of 4 antifungal agents on previously treated Candida spp. AB - This study investigates the impact of different pH values (5.5 and 7.4) on the postantifungal effect (PAFE) and the effect of sub-MIC concentrations (1/4 x MIC) on C. albicans and C. glabrata in the PAFE stage (PAFSE). The PAFE stage was induced by a 1.5 h pretreatment with different doses (1, 4 and 8 x MIC) of 4 antifungal agents. An increase in the pH and/or an increase in the dose of the antimycotic prolonged the duration of the PAFE induced by amphotericin B or 5 fluorocytosine and the PAFSE induced by all 4 antifungal agents in both species. 5-Fluorocytosine and amphotericin B (except for treatment with 1 x MIC at pH 5.5) induced significant PAFEs (0.5-3.0 h and 1.4-4.8 h, respectively), which were increased (to 0.9-3.2 h and 0.8-3.4 h, respectively) by posterior (PLEASE EXPLAIN WHAT YOU MEAN BY THE WORD "POSTERIOR" HERE) exposure to 1/4 X MIC of the respective antifungal agent. Although ketoconazole and fluconazole were not able to induce significant PAFEs, posterior exposure to 1/4 x MIC of each of these 2 azoles led to significant PAFSEs of up to 2.6 h in both yeast species when the concentrations and pH were high enough. PMID- 11200380 TI - Efficacy of amphotericin B colloidal dispersion in the treatment of Mediterranean visceral leishmaniasis in immunocompetent adult patients. AB - Twelve immunocompetent adults with Mediterranean visceral leishmaniasis (VL) were treated with amphotericin B colloidal dispersion (ABCD; 2 mg/kg/d for 7 d). All patients showed rapid clinical response without significant adverse events. Two weeks after therapy they were parasitologically cured and no relapses occurred during 6 months. ABCD is a valid alternative in the management of Mediterranean VL in adult patients. PMID- 11200381 TI - Short therapy with amoxicillin-clavulanate and corticosteroids in acute sinusitis: results of a multicentre study in adults. AB - Evolution of bacterial resistance shortens antibiotic treatment in ENT infections. The efficacy and tolerance of amoxicillin-clavulanate (ACA), with and without associated short steroid therapy, was evaluated in acute sinusitis of adults at a dosage of 1.5 g/d for 5 d vs. 10 d. This multicentre, randomized, double-blind, placebo-controlled study included 433 patients, 417 of whom were suitable for intent-to-treat (ITT) analysis. The therapeutic success rate in the ITT population, assessed according to strict clinical and radiological criteria, was respectively, 80% and 85% in the 5-d and 10-d treatment groups. Due to the statistical risks that were evidenced, the 2 durations of treatment could not be considered equivalent. The analysis of medical history shows that some risk factors (recurrence of sinusitis, previous surgical sinus drainage) seem to promote therapeutic failure and that 5-d treatment is inappropriate in these patients. The persistence of therapeutic success on day 30 was not influenced by the initial duration of treatment. The efficacy and good tolerance of ACA in acute sinusitis in adults were confirmed. Further studies will be needed to define the indications of short treatments better, which seem to be indicated in the absence of specific risk factors. PMID- 11200382 TI - Duration of postoperative antibiotic therapy following revision for infected knee and hip arthroplasties. AB - In the period from 1990 to 1998 28 patients (14 males and 14 females) were treated for infected hip (19 cases) and knee (9 cases) arthroplasties. The median age at index operation was 72 y (range 34-82 y) and at revision surgery 74 y (range 36-83 y). The primary diagnosis was osteoarthritis (16 cases), rheumatoid arthritis (5 cases), failed femoral neck fracture (6 cases) and arthritis secondary to congenital hip dislocation (1 case). Nine cases were infected early, i.e. within 3 months postoperatively, and 19 had late infections. The median interval from index operation to diagnosis of the infected arthroplasty was 18 months (range 1-156 months). Postoperatively, all patients received antibiotics based on susceptibility studies of the causative organism according to culture specimens. The erythrocyte sedimentation rate and CRP level were controlled twice a week during hospitalization and antibiotics were continued until normalization of CRP. The indication for the shift from intravenous to oral antibiotics was a rapid fall in CRP. Antibiotic therapy was terminated when CRP was close to or below 10 mg/l and there was evidence of clinical recovery. Based on the screening of ESR and CRP in this study we believe that CRP is a valuable parameter in deciding when to stop antibiotic therapy. However, it is not clear whether a shorter treatment period is effective or not. PMID- 11200383 TI - PCR in meningoencephalitis diagnosis. AB - Polymerase chain reaction (PCR) detection of a stretch of nucleic acid sequence of microbial origin from a clinical sample is not always diagnostic of disease unless the identified agent is a strict pathogen or its growth is documented. We describe here a case of acute meningoencephalitis in a 21-y-old man, in whom no pathogen was isolated by traditional bacterial or viral culture. Standard DNA PCR performed on the cerebrospinal fluid (CSF) identified the presence of 3 infectious agents: HHV-6, HHV-7 and Mycoplasma pneumoniae. Additional PCRs performed on CSF fractions along with gene transcript analysis proved the bystander role of the 2 herpesviruses and indicated M. pneumoniae as the relevant replicating agent, most likely playing to be a pathogenic role. Until this useful analysis becomes routine, clinicians should deal carefully with DNA PCR results, especially when assessing the aetiological role of agents, such as herpesviruses, which are known to undergo latency. PMID- 11200384 TI - Iatrogenic meningitis: an increasing role for resistant viridans streptococci? Case report and review of the last 20 years. AB - Iatrogenic meningitis following lumbar puncture is a rare event. We present a 52 y-old man who developed symptoms of meningitis within 12 h after spinal anaesthesia. Cerebrospinal fluid cultures grew Streptococcus salivarius partially resistant to penicillin and ceftriaxone. The patient was successfully treated with ceftriaxone and vancomycin and left the hospital with minor sequelae. A literature review of 60 cases revealed the median age of the patients to be 44 y. The median incubation period was 24 h. Most cases occurred after spinal anaesthesia (n = 27), myelography (n = 20) and diagnostic lumbar puncture (n = 5). Organisms were isolated in 52 cases, and streptococcal species were responsible for 33 (63%) of them. An upward trend in resistance of S. viridans isolates is cause for concern and may change empirical treatment strategies. Death was reported in 3 cases (5%) and was associated with Pseudomonas and staphylococcal isolates. The recognition of this entity and the importance of proper infection control measures are underlined. PMID- 11200385 TI - Peritonitis due to Staphylococcus sciuri in a patient on continuous ambulatory peritoneal dialysis. AB - Among the coagulase-negative staphylococci, Staphylococcus sciuri has rarely been described as the aetiology of continuous ambulatory peritoneal dialysis (CAPD) peritonitis. It has been reported in 1 case of endocarditis and has been isolated from peritoneal dialysis fluid in 2 patients. The case reported here describes CAPD peritonitis due to S. sciuri shortly after a previous episode due to S. aureus, showing the necessity to identify coagulase-negative staphylococci to find new species that cause CAPD peritonitis. PMID- 11200386 TI - Spontaneous Escherichia coli meningitis in an adult. AB - Spontaneous meningitis due to gram-negative bacilli (excluding Hemophilus influenzae) is an infrequent infection in adult patients. It usually occurs in patients with underlying immunosuppressive conditions. Most of the cases are due to Escherichia coli and represent a complication of bacteraemia. The infection has a high mortality rate which may be as high as 90%, especially if associated with septicaemia. We report the case of a 53-y-old man with spontaneous, community-acquired Escherichia coli meningitis who was admitted with an unusual presentation. Blood and urine cultures were negative. PMID- 11200387 TI - Isolated splenic tuberculosis presenting with pyrexia of unknown origin. AB - We report a case of a 62-y-old man who presented with fever, malaise and weight loss. He was diagnosed with pyrexia of unknown origin due to tuberculosis of the spleen. Combination anti-tuberculous therapy was administered and fever gradually subsided after 6 weeks. A 12-month course of anti-tuberculous treatment would appear to be appropriate for the treatment of most patients with splenic tuberculosis. PMID- 11200388 TI - Fatal Mycobacterium tuberculosis brain abscess in an immunocompetent patient. AB - A non-HIV-infected 63-y-old woman presented seizures and coma during the course of Mycobacterium tuberculosis infection. Computerized tomography scan led to the diagnosis of a large compressive brain abscess. The patient died with multiorgan failure. Systematic central nervous system investigations should be done in cases of disseminated tuberculosis. PMID- 11200389 TI - Subdural empyema after tooth extraction in which Capnocytophaga species was isolated. AB - We describe a patient with meningitis and a subdural empyema arising from an infection after teeth extraction in which Capnocytophaga species was detected. The patient was a 54-y-old man without any underlying diseases. A computerized tomography scan showed a subdural empyema 21 d after the extraction. PMID- 11200390 TI - Early antibiotic treatment may prevent complete development of Lemierre's syndrome: experience from 2 cases. AB - Lemierre's syndrome is a rare fulminant condition caused by an acute oropharyngeal infection, with secondary septic thrombophlebitis of the internal jugular vein complicated by multiple metastatic infections. Herein we report 2 patients with internal jugular vein thrombosis secondary to oropharyngeal infection, whose clinical course was indolent, and who were asymptomatic shortly after antibiotic therapy was begun. Careful examination of the neck in patients presenting with sore throat could help identify the typical 'cord sign'. In such cases, intravenous antibiotic treatment should be started as soon as possible to prevent development of metastatic infections and septicaemia characterizing Lemierre's syndrome. PMID- 11200391 TI - Brain abscess due to Xylohypha bantiana. AB - A case of brain abscess due to Xylohypha bantiana without any obvious predisposing factors and with the uncommon clinical feature of seizures is presented. PMID- 11200392 TI - E-health, your workforce and you: tales of the early adopters. PMID- 11200393 TI - Substance abuse: myths and realities in the corporate sector. PMID- 11200394 TI - Annual managed care survey. Employers are tied to the inflation track. PMID- 11200395 TI - Do single workers get their fair share? PMID- 11200396 TI - Sherman shares the wealth. PMID- 11200397 TI - Healthy pregnancies start with planning. PMID- 11200398 TI - Datawatch. You may find this hard to believe. PMID- 11200399 TI - Abnormal microheterogeneity of haptoglobin in serum from dogs with various diseases. AB - Changes in the patterns of glycosylation of canine haptoglobin have recently been demonstrated by isoelectric focusing and immunoblotting. Fucosylated fractions of haptoglobin were identified by selective binding of a fucose-specific lectin. In this study, similar changes were found in the serum of 86 of 137 dogs with various inflammatory, autoimmune and neoplastic diseases. Major changes, including fucosylation, were observed in 40 of the dogs and were most frequent in association with autoimmune haemolytic anaemia. All 40 cases had markedly increased concentrations of haptoglobin and decreased concentrations of haemoglobin. Minor changes were found in the other 46 dogs, whereas no changes in glycosylation were detected in the serum of 40 healthy dogs. PMID- 11200400 TI - Prevalence of antibodies to tickborne encephalitis and West Nile flaviviruses and the clinical signs of tickborne encephalitis in dogs in the Czech Republic. AB - Blood sera from 151 dogs from areas of the Czech Republic endemic for human tickborne encephalitis (TBE) were examined for the presence of antibodies to TBE and West Nile (WN) flaviviruses by the haemagglutination-inhibition test Antibodies to TBE virus at titres equal to or exceeding 40 were found in five dogs. Antibodies to WN virus were detected in only one dog that also had a high antibody titre to TBE, suggesting this was a cross-reaction between the two closely related viruses. Three of the dogs (all rottweilers) with a TBE titre of 320 had clinical signs of meningoencephalitis or encephalitis. They all survived after treatment for the clinical signs. It was proved by seroconversion that the disease was caused by the TBE virus in one of these three dogs, and it seems very likely that the virus was responsible for the disease in the other two. PMID- 11200401 TI - Pregnancy following in vitro fertilisation of canine oocytes. PMID- 11200402 TI - Contagious caprine pleuropneumonia in Tanzania. PMID- 11200403 TI - 63,XO/65,XYY mosaicism in a case of equine male pseudohermaphroditism. PMID- 11200404 TI - Progress with PETS. PMID- 11200405 TI - The farming crisis and animal welfare. PMID- 11200406 TI - Neutering of dogs. PMID- 11200407 TI - Lunar influence? PMID- 11200408 TI - FAWC's concerns about leg problems in broilers. Farm Animal Welfare Council. PMID- 11200409 TI - Twenty years on: the small animal practice of the future. PMID- 11200410 TI - Immunohistochemical detection of PrP in the medulla oblongata of sheep: the spectrum of staining in normal and scrapie-affected sheep. AB - Sections of the medulla oblongata from the brains of sheep were examined for prion protein (PrP) by immunohistochemistry. On the basis of the morphology and neuroanatomical distribution of the deposits, distinct disease-associated patterns of PrP deposition were identified in scrapie-affected sheep, suggesting at least four distinct phenotypes of scrapie. In addition, clearly defined patterns of PrP deposition, readily distinguished from the disease-associated PrP deposits, were identified in some normal sheep from scrapie-free flocks. In five sheep, believed to be preclinically affected by scrapie, PrP deposition of a disease-specific type but of restricted distribution was identified, demonstrating the sensitivity of the technique for the diagnosis of scrapie. The neuroanatomical distribution of these early PrP deposits suggest that the route of entry of the scrapie agent into the brain is via parasympathetic motor neurons in the vagus nerve which innervate the gastrointestinal tract. PMID- 11200411 TI - Together we stand: liver units in the new millennium. PMID- 11200412 TI - Adult-to-adult living-donor liver transplantation: a critical analysis. AB - Adult-to-adult living-donor liver transplantation is the most recent achievement in the evolution of strategies to increase donor organ supply. Justification of the procedure has evolved from increased organ-waiting times, wait-list morbidity and mortality of adult transplant candidates. Successful application of adult-to adult living-donor liver transplantation mandates unique surgical, medical, and donor considerations as these procedures predispose to unique complications resulting from anatomic variations, technical considerations, and the transplantation of "partial" grafts. Additionally, because the magnitude of the donor operation is greater and potentially fraught with serious short and long term morbidity and possibly mortality, the utilization of living-donors for adult liver transplantation raises bio-ethical concerns heretofore not encountered. This review explores the current state of adult-to-adult living-donor liver transplantation. PMID- 11200413 TI - Liver transplantation for hepatic and biliary malignancy. AB - The treatment of liver cancer by transplantation has evolved into a process of selecting early stage tumors that have a high likelihood of cure. Carefully selected cirrhotic patients with early hepatocellular cancer (< or = 5 cm. diameter and single; < or = 3 cm. diameter if multiple and 3 or fewer lesions; no vascular invasion) have 5-year actuarial survival rates of approximately 75% after transplantation. Preoperative imaging should be as extensive as necessary to accurately define the characteristics of tumor size, location, and number and exclude signs of extrahepatic involvement. Adjuvant and neoadjuvant chemotherapy became part of treatment protocols in many centers at the same time that more stringent criteria for transplant candidacy were applied to patients with cancer, making it difficult to attribute improved results to the chemotherapy. Nevertheless, neoadjuvant chemoembolization for hepatocellular cancer is logical for patients who may wait long periods before receiving transplants. The fibrolamellar variant of hepatoma is a less aggressive tumor and patients can do well after transplantation, but late recurrences are common. Hepatoblastoma in children can respond very favorably to chemotherapy combined with transplantation. Cholangiocarcinoma remains a dreadful malignancy. The rare cases of insitu cholangiocarcioma in patients who receive transplants for sclerosing cholangitis can be cured, but known cholangiocarcinoma has an exceedingly high rate of recurrence after transplantation alone. Recent work combining chemotherapy and radiation with transplantation has not had dramatic success at improving cure rates. Patients with metastatic neuroendocrine tumors of the liver can receive good palliation by transplantation, but the majority of patients eventually develop recurrent cancer. PMID- 11200414 TI - Liver and small bowel transplantation: therapeutic alternatives for the treatment of liver disease and intestinal failure. AB - Intestinal transplantation is an established life-saving therapy for parenteral nutrition dependent patients suffering from severe complications of parenteral nutrition. Improvements in outcomes over the last decade have occurred with refinements in surgical technique, better immunosuppressive regimens, and clinical experience. The long-term results of intestinal transplantation are not well known and morbidity remains an important obstacle to wider application of this procedure to patients with short bowel syndrome (SBS). This article reviews the indications for intestinal transplantation, the evaluation of potential candidates, therapeutic considerations, postoperative management and common complications experienced by the recipients. PMID- 11200415 TI - Timing of liver transplantation. AB - Under the current environment of liver transplantation, there are several factors to be considered in the timing of liver transplantation. These include expected patient survival with and without liver transplantation, patient's morbidity and quality of life before and after liver transplantation and overall resource utilization. Statistical models have been developed for patients with chronic liver disease, particularly of cholestatic variety. By applying these models in patients being considered for liver transplantation, a window of optimal timing of liver transplantation may be defined in such way that the survival gain is maximized and perioperative mortality minimized. Likewise, a number of pretransplant morbidity indicators such as Child-Pugh score, UNOS status, and renal insufficiency have been found to have a profound influence on post transplant morbidity, thus resource utilization. An increasing number of investigators have measured and documented a dramatic improvement in the quality of life of patients before and after liver transplantation. As the waiting time and uncertainty of the outcome of liver transplantation increase, consideration of these factors may be useful for physicians evaluating transplant candidates to make best-informed decisions in the selection of candidates and timing for liver transplantation. PMID- 11200416 TI - Hepatitis B and C in the liver transplant recipient. AB - Liver disease related to chronic viral hepatitis is the leading indication for orthotopic liver transplantation (OLT) worldwide. The evolution of our understanding of hepatitis B and C infection in the OLT recipient has been rapid in the last decade. The spontaneous risk for viral recurrence after transplantation is high but has been effectively decreased in hepatitis B infected recipients with the use of HBIG and lamivudine with dramatic improvements in patient and graft survivals. HCV recurrence as defined by histologic injury is almost universal although graft or patient outcomes for the first decade after OLT do not appear to be limited by HCV infection for most patients. However, individual patients do suffer severe graft injury and even graft loss due to recurrent HCV. With longer follow up into the second decade, the prevalence of HCV-related graft failure is likely to increase. In addition, the role of different immunosuppressive protocols on disease recurrence requires further study. Thus, although hepatitis B recurrence has been effectively contained by use of HBIG with or without lamivudine, the more intractable problem of managing recurrent HCV has as yet no obvious solutions. Optimal antiviral strategies for hepatitis C post-OLT have yet to be identified. PMID- 11200417 TI - Recurrent primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis after transplantation. AB - Viral hepatitis and malignancy frequently recur after transplantation, but recurrence of primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis is controversial. Differences in study design, number of patients, immunosuppressive treatment, length of follow-up, and criteria for recurrence account for discrepant results. Most patients with suspected recurrent disease are asymptomatic after transplantation. In patients transplanted for PBC, antimitochondrial antibodies frequently persist and do not correlate with disease recurrence; liver biopsy remains the gold standard for diagnosis. Exclusion of other disorders that can mimic PBC is paramount prior to making a diagnosis of recurrent disease. The effects of immunosuppression may modify or delay disease expression within the graft. If PBC recurs, intermediate term patient and graft survival is excellent, but long-term studies will be necessary to address the impact of disease recurrence on the allograft. Due to lack of a diagnostic gold standard, a diagnosis of recurrent PSC after transplantation is difficult to make. An accurate diagnosis of PSC recurrence requires well-defined cholangiographic and histologic criteria. Other disorders that can produce biliary strictures after transplantation should be excluded. As with PBC, the effects of immunosuppression may modify or delay disease expression within the graft; medium-term patient and graft survival is excellent. Recurrence of autoimmune hepatitis is based on clinical, biochemical, serologic, and histologic criteria. As in patients transplanted for PBC and PSC, other conditions that can mimic autoimmune hepatitis require exclusion prior to making a diagnosis of recurrence. Most adult recipients respond to an increase in immunosuppression, whereas pediatric recipients do not respond as well. A cautious approach to withdrawal of immunosuppression is warranted in all patients transplanted for autoimmune hepatitis and the consequences of recurrent disease within the graft will require prolonged follow-up. Future studies should focus on preventive and therapeutic strategies for recurrent autoimmune diseases after transplantation. PMID- 11200418 TI - The mystique of hepatic tolerogenicity. AB - The evolution of clinical transplantation has hinged on 2 seminal turning points. The first was the demonstration in 1953 by Billingham, Brent, and Medawar that chimerism-associated tolerance could be induced deliberately in neonatal mice by infusing adult donor hematolymphopoietic cells. This discovery escalated in a straight line over the next 15 years to successful bone marrow transplantation in humans. The second turning point was the demonstration that organ allografts could self-induce tolerance under an umbrella of immunosuppression, or in some species without immunosuppression. Unfortunately, it was incorrectly concluded by most immunologists and surgeons that bone marrow and organ engraftment involved different immune mechanisms. In a derivative error, it became widely believed that the tolerogenicity of the liver differed fundamentally not only from that of bone marrow but also from that of other whole organs. These errors became dogma and were not corrected until low level donor leukocyte chimerism was found in humans and animals bearing long surviving liver, kidney, heart, and other kinds of allografts. With successful bone marrow transplantation, the trace population consisted of recipient rather than donor leukocytes. Thus, the consequences of organ and bone marrow engraftment were mirror images. From these observations, it was proposed that the engraftment of all kinds of organs as well as bone marrow cells (BMC) involved host versus graft (HVG) and graft versus host (GVH) reactions with reciprocal induction of variable degrees of specific non reactivity (tolerance). The maintenance of the tolerance was an active and ongoing process requiring the persistence of the transplanted fragment of the donor immune system. The immune responsiveness and unresponsiveness to both organ and bone marrow allografts are thought to be governed by the migration and localization of leukocytes. The clarifying principles of tranplantation immunology that have emerged from the chimerism studies are relevant to the adaptive immune response to microbial, tumor, allogeneic, and self antigens. These principles should be used to guide efforts to systematically induce tolerance to human tissues and organs, and perhaps ultimately to xenografts. PMID- 11200419 TI - Prospects for xenotransplantation of the liver. AB - A severe shortage of human livers for allotransplantation has sparked interest in the potential use of animals in lieu of humans as a source of livers, that is xenotransplantation. Xenotransplantation might also provide a means by which recurrence of hepatitis might be averted. Among the types of xenografts that might be undertaken are extracorporeal "xenoperfusion" or perfusion of devices containing xenogeneic hepatocytes, auxiliary liver transplants, bridge liver transplants, and hepatocyte transplants. The hurdles to xenotransplantation of the liver include the immune response of the recipient against the graft, incompatibility of the graft with complex physiologic and biochemical systems of the recipient, and the possibility of transferring infectious agent from the graft to the recipient. Recent progress in characterizing and overcoming these hurdles has encouraged some optimism regarding the ultimate application of xenotransplantation for the treatment of human disease. PMID- 11200420 TI - Immunosuppression in liver transplantation. AB - Prevention of graft rejection while minimizing morbidity remains the single most important objective in liver transplantation. Advances in immunosuppression have provided excellent patient and graft survival with relatively low incidences of acute rejection. However, it is apparent that the toxicity of the present immunosuppressive drugs accounts for much of the morbidity after transplantation. Attention is now being focused on combination drug therapies to reduce morbidity while maintaining the excellent results achieved with present immunosuppressive agents. PMID- 11200421 TI - Recurrence and accelerated progression of hepatitis C following liver transplantation. AB - The patient described had recurrent hepatitis C following OLT. This hepatitis appeared early postOLT and progressed to fibrosing cholestatic hepatitis, a severe form of HCV recurrence. Factors such as genotype 1, high viral load and severe damage on the first postOLT biopsy may indicate a more severe outcome. We have hypothesized that, in parallel to what is known for hepatitis B, this rare form of recurrence was linked to a high expression of virus C proteins in the liver graft. Severe form of hepatitis C recurrence should be treated early with the best currently available treatment which is a combination of IFN and ribavirin. Large series of patients with comparable virological, histological and immunological inclusions criteria are necessary to evaluate the efficacy of this treatment. PMID- 11200422 TI - Retrotransposons: central players in the structure, evolution and function of plant genomes. PMID- 11200423 TI - Scaling the soil-plant-atmosphere continuum: from physics to ecosystems. PMID- 11200424 TI - Seeds of change. PMID- 11200425 TI - Origins of halophilic microorganisms in ancient salt deposits. PMID- 11200426 TI - From protozoa to mammalian cells: a new paradigm in the life cycle of intracellular bacterial pathogens. AB - It is becoming apparent that several intracellular bacterial pathogens of humans can also survive within protozoa. This interaction with protozoa may protect these pathogens from harsh conditions in the extracellular environment and enhance their infectivity in mammals. This relationship has been clearly established in the case of the interaction between Legionella pneumophila and its protozoan hosts. In addition, the adaptation of bacterial pathogens to the intracellular life within the primitive eukaryotic protozoa may have provided them with the means to infect the more evolved mammalian cells. This is evident from the existence of several similarities, at both the phenotypic and the molecular levels, between the infection of mammalian and protozoan cells by L. pneumophila. Thus, protozoa appear to play a central role in the transition of bacteria from the environment to mammals. In essence, protozoa may be viewed as a 'biological gym', within which intracellular bacterial pathogens train for their encounters with the more evolved mammalian cells. Thus, intracellular bacterial pathogens have benefited from the structural and biochemical conservation of cellular processes in eukaryotes. The interaction of intracellular bacterial pathogens and protozoa highlights this conservation and may constitute a simplified model for the study of these pathogens and the evolution of cellular processes in eukaryotes. Furthermore, in addition to being environmental reservoirs for known intracellular pathogens of humans and animals, protozoa may be sources of emerging pathogenic bacteria. It is thus critical to re-examine the relationship between bacteria and protozoa to further our understanding of current human bacterial pathogenesis and, possibly, to predict the appearance of emerging pathogens. PMID- 11200427 TI - N2-dependent growth and nitrogenase activity in the metal-metabolizing bacteria, Geobacter and Magnetospirillum species. AB - Cells of Geobacter metallireducens, Magnetospirillum strain AMB-1, Magnetospirillum magnetotacticum and Magnetospirillum gryphiswaldense showed N2 dependent growth, the first anaerobically with Fe(III) as the electron acceptor, and the latter three species microaerobically in semi-solid oxygen gradient cultures. Cells of the Magnetospirillum species grown with N2 under microaerobic conditions were magnetotactic and therefore produced magnetosomes. Cells of Geobacter metallireducens reduced acetylene to ethylene (11.5+/-5.9 nmol C2H4 produced min(-1) mg(-1) cell protein) while growing with Fe(III) as the electron acceptor in anaerobic growth medium lacking a fixed nitrogen source. Cells of the Magnetospirillum species, grown in a semi-solid oxygen gradient medium, also reduced acetylene at comparable rates. Uncut chromosomal and fragments from endonuclease-digested chromosomal DNA from these species, as well as Geobacter sulphurreducens organisms, hybridized with a nifHDK probe from Rhodospirillum rubrum, indicating the presence of these nitrogenase structural genes in these organisms. The evidence presented here shows that members of the metal metabolizing genera, Geobacter and Magnetospirillum, fix atmospheric dinitrogen. PMID- 11200428 TI - Identification of conserved traits in fluorescent pseudomonads with antifungal activity. AB - A collection of 29 fluorescent pseudomonads, some with known biological control activity against a range of phytopathogenic fungi, were characterized phenotypically and genotypically by comparing carbon source utilization patterns, suppression of Pythium ultimum both in planta and in vitro and the potential to produce known secondary metabolites. Fatty acid profiling and restriction fragment length polymorphism (RFLP) analysis of the ribosomal DNA operon (ribotyping) were used to determine the diversity of isolates. A small group of genetically related Pseudomonas spp. with similar properties was identified; each isolate produced a diffusible bioactive product in vitro and was active against Pythium ultimum in planta. However, other isolates that were able to suppress damping off disease but did not inhibit hyphal extension in vitro clustered outside this group. Phenotypic analyses revealed that the accumulation of C17:0 cyclopropane fatty acid (17CFA) and the production of hydrogen cyanide correlated significantly with biological control activity and with the antagonism of fungal development. The potential of 17CFA as a marker for the selection of fluorescent pseudomonads with biocontrol agent (BCA) potential was demonstrated by the isolation of a novel active strain. This was selected after the screening of 13 clonal groups of fluorescent pseudomonads identified from 500 isolates from the phytosphere of sugar beet. Levels of 17CFA synthesis possibly reflect the efficacy of the rpoS allele in particular strains. PMID- 11200429 TI - Online and in situ monitoring of environmental pollutants: electrochemical biosensing of cadmium. AB - Online sensitive monitoring of gene expression is essential for understanding microbial life and microbial communities, especially under stress-inducing conditions, such as the presence of environmental pollutants. We describe here a novel use of promoter-based electrochemical biosensing for online and in situ monitoring of gene expression in response to pollutants. As a model system, we used a cadmium-responsive promoter from Escherichia coil fused to a promoterless lacZ gene, which was monitored using an electrochemical assay of beta galactosidase activity. This whole-cell biosensor could detect, within minutes, nanomolar concentrations of cadmium in water, sea water and soil samples, and it can be used for continuous online and in situ monitoring. PMID- 11200430 TI - Green algal extracellular products regulate antialgal toxin production in a cyanobacterium. AB - Many bacterial genes and virulence factors are regulated by interbacterial and/or host-parasite chemical signals. We demonstrate that toxin production by a free living freshwater cyanobacterium is regulated in part by the presence of extracellular products of a eukaryotic green alga. In growth experiments, extracellular products made by the cyanobacterium Anabaena flos-aquae contained both anatoxin and microcystin, and significantly reduced the yield of Chlamydomonas reinhardtii, a green alga. Based on experiments in which we added purified toxins to C. reinhardtii cultures, we believe that microcystin was responsible for the growth reduction. A. flos-aquae produced anatoxin constitutively when grown alone, but anatoxin concentration increased in the presence of C. reinhardtii elicitors. Microcystin accumulation depended on the growth phase; however, high concentrations of C. reinhardtii extracellular products completely inhibited microcystin accumulation. Our results demonstrate that cyanobacterial toxin production may be regulated by complex growth phase dependent and environmental chemical cues, and suggest that secreted chemicals can mediate the outcome of competition between the cyanobacterium A. flos-aquae and the green alga C. reinhardtii. PMID- 11200431 TI - The biogeochemical controls of N2O production and emission in landfill cover soils: the role of methanotrophs in the nitrogen cycle. AB - Emissions of N2O from cover soils of both abandoned (> 30 years) and active landfills greatly exceed the maximum fluxes previously reported for tropical soils, suggesting high microbial activities for N2O production. Low soil matrix potentials (<-0.7 MPa) indicate that nitrification was the most likely mechanism of N2O formation during most of the time of sampling. Soil moisture had a strong influence on N2O emissions. The production of N2O was stimulated by as much as 20 times during laboratory incubations, when moisture was increased from -2.0 MPa to -0.6 MPa. Additional evidence from incubation experiments and delta13C analyses of fatty acids (18:1) diagnostic of methanotrophs suggests that N2O is formed in these soils by nitrification via methanotrophic bacteria. In a NH3(g)-amended landfill soil, the rate of N2O production was significantly increased when incubated with 100 ppmv methane compared with 1.8 ppmv (atmospheric) methane. Preincubation of a landfill soil with 1% CH4 for 2 weeks resulted in higher rates of N2O production when subsequently amended with NH3(g) relative to a control soil preincubated without CH4. At one location, at the soil depth (9-16 cm) of maximum methane consumption and N2O production, we observe elevated concentrations of organic carbon and nitrogen and distinct minima in delta15N (+1.0%) and delta13C (-33.8%) values for organic nitrogen and organic carbon respectively. A delta13C value of -39.3% was measured for 18:1 carbon fatty acids in this soil, diagnostic of type II methanotrophs. The low delta15N value for organic nitrogen is consistent with N2 fixation by type II methanotrophs. These observations all point to a methanotrophic origin for the organic matter at this depth. The results of this study corroborate previous reports of methanotrophic nitrification and N2O formation in aqueous and soil environments and suggest a predominance of type II rather than type I or type X methanotrophs in this landfill soil. PMID- 11200432 TI - Cultivatable microbial biodiversity: gnawing at the Gordian knot. AB - Rapid and inexpensive sorting of bacterial isolates may be achieved using Fourier transform infrared spectroscopy (FT-IR), a method that has hitherto been applied to identification and classification. The comprehensive characterization of environmental samples requires the isolation of large numbers of isolates using different growth media and growth conditions. In such cases, sorting the isolates is critical before isolates are subjected to more detailed studies. Using FT-IR, isolates are grown under standardized conditions, and 100 strains can be tested within less than 8 h. Chemotaxonomic and molecular characterization of members of clusters emerging from FT-IR analysis either at a level of spectral distance values below 20-30 (analysis of region 600-800 cm(-1), average linkage algorithm) or at spectral heterogeneity values below 75 (regions 1,200-900, 3,000-2,798 and 901-698, scaling to first region, Ward's algorithm) reveals great similarities in fatty acids and 16S rDNA sequences. As judged from riboprinting analyses and fatty acid analyses, FT-IR analysis is able to unravel intraspecific subclustering. The example used in this study of 100 isolates from a mat system, Lake Fryxell, Dry Valleys, Antarctica, selected from a larger number of isolates, picked mainly on the basis of colony pigmentation and form, reveals the utility of the method for identifying the number of putative species quickly. The method described is able to select strains rapidly that represent clusters at the specific and intraspecific level for subsequent characterization. PMID- 11200433 TI - Retrotransfer of DNA in the rhizosphere. AB - Retrotransfer of DNA refers to the phenomenon by which a plasmid travels from a host strain to a recipient one and returns to the original host, bringing with it DNA from the recipient. The resultant host strain with DNA from the recipient is called a retrotransconjugant. The retrotransfer phenomenon mediated by the TOL plasmid pWW0 and other plasmids has been documented on plates under optimal laboratory culture conditions, but never under natural conditions. In this work, we show that retrotransfer mediated by the IncP9 TOL pWW0 plasmid occurs in the rhizosphere, a niche in which the continuous supply of nutrients via root exudates allows cells to reach a high density. This suggests that this unusual sexual fertilization may be of great importance in lateral gene transfer. We also show that retrotransfer of DNA seems to require co-integration of the plasmid and the host chromosome and subsequent resolution, because a TOL plasmid with a mutation in the tnpR gene, encoding the resolvase of the Tn4653 of the TOL plasmid, was self-transferred between Pseudomonas strains, but unable to mobilize chromosome. PMID- 11200434 TI - Characteristics of attachment and growth of Thiobacillus caldus on sulphide minerals: a chemotactic response to sulphur minerals? AB - To further our understanding of the ecological role of sulphur-oxidizing microorganisms in the generation of acid mine drainage (AMD), growth and attachment of the chemoautotrophic sulphur-oxidizing bacterium, Thiobacillus caldus, on the sulphide minerals pyrite, marcasite and arsenopyrite was studied. Growth curves were estimated based on total cells detected in the system (in suspension and attached to mineral surfaces). In general, higher cell numbers were detected on surfaces than in suspension. Fluorescent in situ hybridizations to cells on surfaces at mid-log growth confirmed that cells on surfaces were metabolically active. Total cell (both surface and solution phase) generation times on pyrite and marcasite (both FeS2) were calculated to be approximately equals 7 and 6 h respectively. When grown on pyrite (not marcasite), the number of T. caldus cells in the solution phase decreased, while the total number of cells (both surface and solution) increased. Additionally, marcasite supported about three times more total cells (approximately equals 3 x 10(9)) than pyrite (approximately equals 8 x 10(8)). This may be attributed to the dissolution rate of marcasite, which is twice that of pyrite. Epifluorescent and scanning electron microscopy (SEM) were used to analyse the cell orientation on surfaces. Results of Fourier transform analysis of fluorescent images confirmed that attachment to all three sulphides occurred in an oriented manner. Results from high-resolution SEM imaging showed that cell orientation coincides with dissolution pit edges and secondary sulphur minerals that develop during dissolution. Preferential colonization of surfaces relative to solution and oriented cell attachment on these sulphide surfaces suggest that T. caldus may chemotactically select the optimal site for chemoautotrophic growth on sulphur (i.e. the mineral surface). PMID- 11200436 TI - Phylogenetic relationship and antifouling activity of bacterial epiphytes from the marine alga Ulva lactuca. AB - It is widely accepted that bacterial epiphytes can inhibit the colonization of surfaces by common fouling organisms. However, little information is available regarding the diversity and properties of these antifouling bacteria. This study assessed the antifouling traits of five epiphytes of the common green alga, Ulva lactuca. All isolates were capable of preventing the settlement of invertebrate larvae and germination of algal spores. Three of the isolates also inhibited the growth of a variety of bacteria and fungi. Their phylogenetic positions were determined by 16S ribosomal subunit DNA sequencing. All isolates showed a close affiliation with the genus Pseudoalteromonas and, in particular, with the species P. tunicata. Strains of this bacterial species also display a variety of antifouling activities, suggesting that antifouling ability may be an important trait for members of this genus to be highly successful colonizers of animate surfaces and for such species to protect their host against fouling. PMID- 11200435 TI - Disruption of the Paenibacillus polymyxa levansucrase gene impairs its ability to aggregate soil in the wheat rhizosphere. AB - Inoculation of wheat roots with Paenibacillus (formerly Bacillus) polymyxa CF43 increases the mass of root-adhering soil. We tested the role of levan, a fructosyl polymer produced by strain CF43, in the aggregation of soil adhering to wheat roots. The P. polymyxa gene homologous to the Bacillus subtilis sacB gene encoding levansucrase was cloned and sequenced. The corresponding gene product synthesises high molecular weight levan. A P. polymyxa mutant strain, SB03, whose sacB gene is disrupted, was constructed using heterogramic conjugation. Effects of wheat inoculation with the wild type and the mutant strain were compared using two different cultivated silt loam soils in four independent pot experiments. Roots of wheat plantlets inoculated with CF43 or SB03 were colonized after 7-14 days at the same level, and root and shoot masses were not significantly different from those of the non-inoculated control plants. The ratio of root adhering soil dry mass to root tissue dry mass was significantly higher for plants inoculated with strain CF43 than for those inoculated with mutant strain SB03: +30% in Orgeval soil and +100% in Dieulouard soil. Thus the levan produced by P. polymyxa is implicated in the aggregation of root-adhering soil on wheat. PMID- 11200437 TI - Microbes in biocontrol. An annotated selection of World Wide Web sites relevant to the topics in Environmental Microbiology. PMID- 11200438 TI - Pseudomonas entering the post-genomic era. PMID- 11200439 TI - [Blood protein technological industrial developments as a mirror of fundamental studies bgy the Institute of Biochemistry of the Ukrainian National Academy of Sciences]. AB - We have examined the technology for an industrial chromatographic production highly purified factor VIII concentrate intended for therapy of the hemophilia A and characterized this factor VIII. The final product has been prepared from cryoprecipitate of pooled human plasma using a large-scale procedure combining three conventional chromatographic steps based on AEM and CEM ion exchange and SPG or SHR gel filtration chromatography. The specific activity of the product was 459 +/- 19 IU factor VIII/mg protein (n = 10), corresponding to a purification factor of about 15,000. The concentrate was free of the fibrinogen, alpha-2-macroglobulin, alpha-1-acidglycoprotein, haptoglobin. Only three contaminants could be detected: fibronectin, immunoglobulins A and G (about 0.020, 0.004 and 0.034 microgram/IU factor VIII, respectively). The purity of the final product was confirmed by SDS polyacrylamide gel electrophoresis, cellulose acetate electrophoresis, Grabar-Williams immunoelectrophoresis, and bidimensional immunoelectrophoresis. Another examination was concern to the technology for an industrial chromatographic production highly purified factor IX concentrate intended for therapy of the hemophilia B and characterized this factor IX. The final product has been prepared from pooled human plasma using a large-scale procedure combining four conventional chromatographic steps based on AEM ion exchange, AFM affinity and SGS gel filtration chromatography. The specific activity of the product was 149 +/- 10 IU factor IX/mg protein (n = 10), corresponding to a purification factor of about 9000. The concentrate was free of the vitamin K-dependent clotting factors II, VII and X and of proteins C and S. Most of possible contaminants were absent in this new product. High-molecular weight kininogen, factor VIII, XI, XII or prekallikrein were not detected. There were no activated factors, such as factors IXa and Xa, no thrombin and no phospholipids. Only two contaminants could be detected: C4 and inter-alpha trypsin inhibitor (about 0.8 and 1.2 mg/IU factor IX, respectively). The purity of the final product was confirmed by SDS polyacrylamide gel electrophoresis, cellulose acetate electrophoresis, Grabar-Williams immunoelectrophoresis, and bidimensional immunoelectrophoresis. Thrombogenicity tests in rabbits revealed that the high purified factor IX by Institute of Biochemistry technology tested had a lower thrombogenic power than the commercial factors IX tested. The concentrate has been subjected to a special solvent--detergent treatment for definite time and temperature during its production to virus inactivation (it will be describe in following special examination). These data demonstrate that a highly purified therapeutic clotting factor VIII and IX concentrates can be prepared from human plasma by conventional chromatographic methods developed by Institute of Biochemistry of NAS of Ukraine and Combio Ltd. PMID- 11200440 TI - [Biological properties of the mechanism of "marine" phospholipids containing omega-3 fatty acids]. AB - The Laboratory mainly deals with the development of biologic technologies for producing physiologically active lipid-protein-nature compounds from marine organisms containing omega-3 fatty acids (that are membrane components) with further evaluation of their action both in the normal state and in some simulated pathologic states as well as with creation of new preparations for application in medicine and agriculture on their basis. As a result of the experiments performed, a technology for producing two biologic preparations, namely, surface active compounds (phospholipids) and a nucleopeptid-lipid complex, exhibiting a specific action, was developed. The phospholipid complex, being surface-active in composition, was characterized as a complex possessing some surfactant-type properties and displaying an antioxidant and a membrane-stabilizing effect. On the basis of the complex including marine phospholipids with omega-3 fatty acids, the preparation "Phylomek", which is the concentrate of essential marine phospholipids, and the preparation "Morephyl", which is a marine agent with surfactant-type effect, intended for animals and poultry, were created. The ingredients of the nucleopeptid-lipid complex were identified, and its effect on the increase of testosterone levels in the blood of old and sick animals was determined. A stimulating agent of genital hormones secretion was recommended for application in the geriatrics in the case of genital function disturbance and presenilation. A fraction similar in chemical content and specific activity, found in the velvet antlers, was used as the base of the biologic preparation "Pantheron". The natural complexes of marine phospholipids were shown to be able to change the composition of lipids of membranes, but the intensity of these changes differed in cells differing in function. In the study of the biochemical mechanism of correction of disturbances in the cell membranes under an oxidative stress, the interrelation between the composition of lipids of membranes, their oxidation, and the content of natural antioxidants was determined. The reparative effect of marine phospholipids on the cell membranes under progressing pathology, caused by the restoration of the composition of phospholipids, by increases in the activities of antioxidant enzymes (SOD, catalase), and by a decrease of the accumulation of LPO products, was established. Under interaction of marine phospholipids and alpha-tocopherol, synergism was noticed, the antioxidant potential of the investigated substances and their membrane-stabilizing effect increased. The phospholipids with various residues of PUFA in the molecule were found to affect the inhibition and oxidation processes, as well as the modelling of lipid membranes. This is especially true for arachidonic and docosahexaenoic acids, the ratio of which changes under the oxidative stress. At administration of phospholipids omega-3, their ratio decreases due a decrease in the level of unetherificated PUFA. The main changes of the PUFA were found to occur in phosphatidylethanolamine isolated from microsomes. The particular role of phosphatidylethanolamine and arachidonic acid in the reparation of membranes under the action of phospholipids PUFA omega-3 and alpha-tocopherol was noted. PMID- 11200442 TI - [Physiologic functions of vitamin D3 and its metabolism in the body in normal states and in some pathologies]. AB - In the review there are some results of investigations of the laboratory summarized on the mechanisms of vitamin D3 metabolism and its functioning in organism; investigation of infringement of mineral, lipid and protein metabolic processes with vitamin D3 deficiency and with different pathologies and the ways of their regulation as well as the data about some new high-effective forms of vitamin D3 for their implementation in medicine and agriculture. PMID- 11200441 TI - [Basis for the historical stages for studying the biochemistry of vitamins. Noncoenzymatic mechanisms of vitamin B1]. AB - Biochemistry of vitamins is one of the leading trends in the fundamental researches of A. V. Palladin Institute of Biochemistry from the moment of its foundation in 1925. The Laboratory of Vitamins Biochemistry was organised in 1994, it was reorganized into the Department of Vitamins Biochemistry in 1966, and later it was renamed as the Department of Coenzymes Biochemistry. Now the investigations at the Coenzymes Biochemistry Department headed (from 1986) by G. V. Donchenko, Corr.-Member of the National Academy of Sciences of Ukraine, are directed to estimation of vitamins A, E, B1 and PP action molecular mechanisms. Investigation of specific protein-acceptors of vitamins and their biologically active derivatives is a contemporary and effective methodological approach to the estimation of some molecular mechanisms of vitamins action on cellular metabolism. Considering the challenging theoretical and practical aspects of the further fundamental investigation development in the molecular vitaminology the following items are currently being worked in the Department last time: 1. Study of some molecular mechanisms of thiamine and vitamin PP neurotropic action. These investigations are oriented to clearing some new aspects of noncoenzymic mechanism of its influence on the nervous cell functioning both in the norm and at some nervous diseases. 2. Study of some molecular mechanisms of regulation by means of fat-soluble vitamins A, E and their specific proteins-acceptors of DNA, RNA and protein biosynthesis in the nuclei and mitochondria of actively proliferous cells. These investigations are aimed to the estimation of molecular mechanisms of fat-soluble vitamins participation in the regulation of DNA dependent synthesis of RNA, RNA-polymerase activity, mechanism of their anticancerogenous effect, vitamin E participation in the realisation of nuclear genetic information. 3. Study of intracellular protein-receptors, which take part in realisation of vitamins and their biologically active derivatives functions in the human and animals' organism. The investigations, directed to study of a role of retinol-binding proteins in exchange of the vitamin A and in biosynthesis of DNA, RNA and proteins, the role of tocopherol-binding proteins in realisation of biological action of vitamin E in cells and thiamine-binding proteins in realisation of neurotropic action of vitamin B1 are actively developed. 4. Investigation of mechanisms of antioxidizing and antiradical biological action of vitamin D3, ecdisterone and related biologically active compounds. Basing on the fundamental researches some vitamins preparations have been created, such as "Carotin-M", "Cardiovit", "Evit-1", "Soevit", "Metovit", "Caratel'ka" and others. The results of fundamental investigation of noncoenzymic thiamine function led us to elaboration of a new hypothesis about molecular mechanism of vitamin B1 neurotropic action. According to the hypothesis the thiamine high neuroactivity is a result of existence in the nervous ending a specific mobile thiamine pool and connection thiamine metabolism with nervous cell membrane potential and acetylcholine metabolism. PMID- 11200443 TI - [Immunosensors: sources of origin, achievements and perspectives]. AB - The analysis of the recent data in the literature and results of investigations in the field of the development and study of function efficiency of different types of immune sensors, that are performed at the Department of Biochemistry Sensory and Regulatory Systems of the A. V. Palladin Institute of Biochemistry of Ukrainian National Academy of Sciences are presented. Sources of origination and perspectives of the devlopment of biosensors are discussed as well. The paper also gives an overview of main research projects at the Department, mainly in the filed of biosensors. They include development of the scientific bases for the creation of a new generation of chemo- and biosensors for their application in medicine and ecology. Multi-immune, multi-enzyme and combined multi-parametrical sensors can provide express analyses in laboratory and field conditions with the purpose to perform immune chemical diagnostics of diabet, kidney diseases, immune defficiencies, autoimmune, allergic, pre-infarction and pre-tumor states as well as to control total toxicity of the environment and identification of main types of toxic elements in it. The investigations are based on the latest achivements in the field of physics, chemistry, information technology and electronics with the use of different types of planar electrodes, ion sensitive field effect transistors (ISFETs), semiconductor capacitive structures, termistors, optrodes, piezocrystalls and application of such methods and effects as laser correlation spectroscopy, chemiluminescence, fluorescence, surface plasmon resonance, photoluminescence of porous silicon, interferometry, evanescent wave technique, nonemmiting energy transfer and holography. PMID- 11200444 TI - [Institute of Biochemistry and the development of molecular biophyics in the Ukraine]. AB - The development of molecular biophysics research in Ukraine is reviewed with historical perspective. Vladimir Belitser and his school were among the pioneers in the studies of protein denaturation and assembly of intermolecular structures. New methods of research of protein conformational transitions and dynamics at equilibrium have been developed at the Palladin Institute of Biochemistry. Presently, the biophysics aspects in different areas of protein research are actively explored. The studies of protein folding in both experimental and theoretical aspects promise especially good prospects. PMID- 11200445 TI - [Division of Regulatory Systems of Cells of the Institute of Biochemistry of the Ukrainian National Academy of Sciences (L'viv). History, achievements and perspectives]. AB - A short review presented deals with the history of biochemistry development in the western regions of Ukraine. Two principal biochemical schools were founded here by J. Parnas (1884-1949) and S. Gzhytskiy (1900-1976). While most of the students and collaborators of Prof. J. Parnas left for Poland and other western states, those ones of Prof. S. Gzhytskiy stayed in Lviv and other scientific centers of Ukraine. In 1979 Prof. S. Kusen (one of Gzhytskiy's former students and collaborators) and Prof. G. Shavlovsky headed two scientific departments founded in Lviv at O. V. Palladin Institute of Biochemistry. This event could be considered as the beginning of modern biochemistry development in the western regions of Ukraine. Since 1992 in Lviv there exists the Division of Regulatory Cell Systems of O. V. Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine headed since 1995 by Prof. R. Stoika. Four Departments work in the structure of this Division: 1) the Department of Biochemistry of Cell Differentiation headed in 1979-1997 by S. Kusen and since 1997 by L. Drobot; 2) the Department of Regulation of Cell Proliferation created in 1993 and headed by R. Stoika; 3) the Department of Biochemical Genetics created in 1988 and headed by A. Sibirny; 4) the Department of Regulation of Synthesis of Low Molecular Compounds headed in 1979-1996 by G. Shavlovsky and since 1996 by D. Fedorovych. Division of Regulatory Cell Systems is presently the leading scientific center in Ukraine in the study of the biochemical mechanisms of proliferation, differentiation and apoptosis of normal and tumour cells and in the development of effective biotechnological processes for obtaining the biologically active substances using yeast. Numerous publications of its collaborators in the high impact factor scientific magazines as well as the realisation of the international grants confirm this statement. Taking into account the high level of scientific research and availability of highly skilled scientists at the Division in 1999 the Presidium of the National Academy of Sciences of Ukraine took a resolution to transform the Division into the Institute of Cell Biology of the National Academy of Sciences of Ukraine, which was founded in 2000 on the basis of the Division. PMID- 11200446 TI - [Metabolic engineering in design of cellular elements of biosensors]. AB - An extended definition of the term "metabolic engineering" is given and main spheres of its using in fundamental studies and modern biotechnology are discussed in this article. Emphasis is made on specific using the approaches of metabolic engineering in construction of the cell elements of sensors based on the use of mutant and chemically modified cells of methylotrophic yeasts. This investigation is designed in the laboratory of Biochemical Genetics of the Division of Cell Regulatory Systems, A. V. Palladin Institute of Biochemistry. Genetic and chemical modifications have allowed to provide some directed changes in cell sensoring output toward methanol, ethanol and formaldehyde that result in enhanced selectivity and shortened time-output of the corresponding potentiometric and amperometric sensors. PMID- 11200447 TI - [History of O.V. Palladin Institute of Biochemistry of the Ukrainian National Academy of Sciences]. PMID- 11200448 TI - [My first steps in science at the Institute of Biochemistry]. PMID- 11200449 TI - [Reminiscences about my father]. PMID- 11200450 TI - [Good examples are inherited]. PMID- 11200451 TI - [Basic directions of research of the department of lipid biochemistry]. AB - The review deals with the scientific activity of the Department of Biochemistry of Lipids of the Palladin Biochemistry Institute of the National Academy of Sciences of Ukraine. The estimation of the functional role of some major lipids and of the minor lipid components, namely, N-acylethanolamines (NAE), is the main problem of the scientific investigations of the Department. The role of some lipids in the pathogenesis of diseases accompanied by the oxidative stress was also studied. The Department was the first to find and identify NAE in neuroblastoma C1300 N18 cells. It was shown that NAE with long saturated acyl chains inhibited veratridine-activated fast sodium channels. NAE also activated uterine plasma membrane smooth muscle Ca2+, Mg(2+)-ATPase, and inhibited Fe(2+) induced free radical oxidation in mitochondria. The results of these investigations served as a basis for development of pharmacological substances with membrane protective properties. It was shown that, at different diseases accompanied by the oxidative stress, a significant change in the lipid composition of cell membranes occurred. Sometimes these changes were adaptive in character, which favored the cell viability adaptation to pathological conditions. The new level of regulation of adaptive reactions can be accompanied by the development of additive injuries of cell viability, which may be caused by the altered level of biologically active cell lipid components. Based on the results of these investigations, the preparation intended for treatment of male infertility was developed. The pharmacological substances intended for treatment of morphine abuse and acute ischemia of myocardium were created. PMID- 11200452 TI - [alpha-Latrotoxin as an instrument for studying neurosecretions]. AB - alpha-Latrotoxin, a presynaptic toxin from black widow spider venom Latrodectus mactans tredecimguttatus, triggers exocytosis in a variety of neurosecretory cells both in the presence and absence of calcium in the medium. The toxin interacts with two types of membrane the receptors which belong to different families of neuronal proteins and have different structures. Calcium-dependent receptor of alpha-latrotoxin is identified as neurexin I alpha and belongs to the family of neurexins. This family is selectively expressed in nerve tissue. The calcium-independent receptor of alpha-latrotoxin belongs to the family of G protein-coupled receptors and proteins which homologous to it are found in heart, lung, kidney and spleen tissues. As a result of alpha-latrotoxin interaction with membrane receptor in the calcium medium the toxin forms the ionic channels in plasmalemma and enhances its calcium permeability. The effects of alpha latrotoxin on exocytosis in the calcium and calcium-free media and question concerning coupling of channel-forming and secretogenic properties of alpha latrotoxin are discussed. PMID- 11200453 TI - [Modulation of Na+-K+-ATPase by calcium ions]. AB - The modulatory effects of calcium ions on highly active Na+, K(+)-ATPase from calf brain and pig kidney tissues have been studied. The inhibitory action of Ca2+free on this enzyme depends on the level of ATP (but not AcP). The reduction of pH from 7.4 to 6.0 noticeably increases, but the elevation of pH to 8.0, in its turn, decreases the inhibition of ATP-hydrolyzing activity by calcium. With the increase of K+ concentration (in contrast to Na+) the sensibilization of Na+, K(+)-ATPase to Ca ions is observed. In the presence of potassium ions Mg2+free effectively modifies the inhibitory action of Ca2+free on this enzyme. Ca2+free (0.16-0.4 mM) decreases the sensitivity of Na+, K(+)-ATPase to action of the specific inhibitor ouabain in the presence of ATP. In the presence of AcP (phosphatase reaction) such a change of enzyme sensitivity to ouabain isn't observed. The influence of membranous effects of Ca2+ on the interaction of Na+, K(+)-ATPase with the essential ligands and cardiosteroids is discussed. PMID- 11200454 TI - [Kinetics and energy aspects of the effect of incubation medium dielectric permeability on the catalytic and transporting activity of Mg2+-ATP-dependent Ca2+ pump plasma membranes]. AB - The results suggest that changes in polarity of the incubation medium markedly affect the activity of transport Ca2+, Mg(2+)-ATPase solubilized from smooth muscle cell plasma membranes and that the electrostatic interactions between the enzyme active center and specific ligands (MgADP-, in particular) significantly contribute to the energetics of ATP hydrolysis. PMID- 11200455 TI - [O.V. Palladin Institute of Biochemistry of the Ukrainian National Academy of Sciences--75 years]. AB - The article deals with a short record including the information about the history of creation and main developmental stages of the first and presently the single in Ukraine Palladin Institute of Biochemistry of National Academy of Sciences of Ukraine. The record contains the main achievements of the Institute scientific subdivisions for the 75 years period of their creative work in the field of the most urgent problems of fundamental and applied biochemistry. As well it displays the information about comprehensive and extensive publishing and educational activity conducted by the staff,, the work on training the scientific manpower of the highest qualification--Doctors of Science (D.Sc.) and Philosophy Doctors (Ph. D.), active participation of the research scientists in attracting to science the talented young people representing the students and school-children taking interest in the biological chemistry. The article shows the great role of the Institute famous scientists-biochemists in forming some scientific schools on functional biochemistry acknowledged in the world biochemistry. There are also some data about the each of nine scientific departments of the Institute for the period of last 20-25 years of their activity in the field of the most urgent problems of the contemporary biochemistry. These are the following Departments: Neurochemistry, Metabolism Regulation, Muscular Biochemistry, Protein Structure Functions, Coenzymes Biochemistry, Enzymes Chemistry and Biochemistry, Molecular Immunology, Biochemistry of Lipids, Sensor and Regulator Systems Biochemistry. There is also a short review regarding the history of foundation, development and scientific achievements of the Institute division in L'viv including four scientific departments: Biochemistry of Cellular Differentiation, Biochemical Genetics, Regulation of Low Molecular Compounds Synthesis, Regulation of Cells Differentiation. PMID- 11200456 TI - [Department of Molecular Immunology--25 years]. AB - Department of Molecular Immunology of Palladin Institute of Biochemistry was founded 25 years ago as the Laboratory of Immunochemistry uniting, at the beginning, a small group of scientists. In 1982 the Laboratory was transformed into the Department of Molecular Immunology. The first research was made on studding the biological effect and the mechanisms of action of phosphonates and bisphosphonates--phosphororganic analogues of inorganic pyrophosphate or closely related in structure molecules having P-C bond instead of P-O bond. As a result the immuno-modulatory activity of methylene-bis-phosphonic acid was discovered and a set of immuno-vector, immuno-toxin and anti-tumour constructs were designed. The researchers of the Department were the first in the USSR who started the biochemistry of activated lymphocytes, immunochemical analysis of peptides and proteins, implemented immunoenzyme methods and cytofluorimetry to study immunocompetent cells. In particular, monoclonal and polyclonal antibodies were obtained and used to study the antigenic structure of neurotoxin apamin, cytochrome c, neurospecific proteins S-100 and 14-3-2, nicotinic acetylcholine receptors, pertusis and diphtheria toxins, different antigens of Mycobacterium bovis and of fibrin(ogen) and its fragments and others. The new site of fibrin polymerization was localized. The novel information about the nature of polyreactive immunoglobulins and their influence on the development of the humoral immune response was obtained. A range of reagents for immunodiagnostic tests were developed as the outcome of this research work. The negative effect of small doses of radiation on natural immunity in people working during the cleaning of Chernobyl nuclear plant was first demonstrated by the researchers of the Department in co-operation with their colleagues from a couple of Kiev immunology laboratories. In particular the suppression of NK cells function and structure was shown. PMID- 11200457 TI - [Mechanism of metabolic adaptation]. AB - The paper presents results of investigations on some mechanisms of metabolic adaptation in mammals. There are four sections in the tissue metabolic system of acid-base homeostasis: polyamines as factors of metabolic adaptation; significance of carbon dioxide for metabolic response formation in hypobiosis; polyamines metabolism in hypobiosis. Peculiarities of intermediate metabolism have been analyzed in animal tissues under the changes in H+, CO2 and HCO3- concentrations. Basing on a new interpretation of the experimental data and detected regularity in the metabolism, conclusion on the existence of a new acid base homeostasis system in the tissues has been made. The results of polyamines metabolism investigations in the mammals under the stress have been described. The experimental data make us to believe that changes in polyamines synthesis and ODC activity in particular, is a part of stereotype nonspecific response to any stress impacts and one of the factors of cell metabolic adaptation. Some new data on mechanisms of formation and control of metabolic status of animals in the natural and artificial hibernation have been presented. The key idea is that in the state of hypobiosis the carbon dioxide (HCO3-) appears as a regulatory factor of metabolic adaptation, which is able to realize its action directly via affecting numerous biochemical events. The participation of polyamines in adaptive metabolic response to hybernation factors is suggested. Some peculiarities of ornithine decarboxilase and transglutaminase activity during the different stages of genuine and artificial hypobiosis have been demonstrated. PMID- 11200458 TI - [Department of Protein Structure and Function--Volodimir Oleksandrovich Bielitser School of the Ukrainian Academy of Sciences. Studies on structure of fibrin fiber structure and mechanism (1975-1987]. AB - In this short historical review the records about foundation and research activity of the Department of Structure and Function of Protein--school of V. A. Belitser, Member of the National Academy of Sciences of Ukraine are presented. V. A. Belitser was the founder and indispensable chief of the department since the date of its creation (1944) till 1987. The main research interests (1975-1987) of the department were focused at the investigation of structure, biological function of the fibrinogen-fibrin system, mechanisms of the network assembly and of the fibrin fibers structure. Studying the molecular mechanisms of the fibrin fiber assembly, it was shown that the specificity of the building structure was shown is determined by the specific reactive sites with strong affinity of the molecules. The activity of the sites was investigated on protein molecules as well as the fragments. The physical nature of the bonds created by the active sites, that appearing during in the process of fibrinogen activation by thrombin, was revealed. Examination of the fibrin assembly in cooperation with electronmicroscopists and studies of the complex formation between active fragments and fibrin monomer were summarized. Both the fibrin monomer polymerization and protofibril lateral association are presented as two stages in the assembly of the fibrin network. In the research of the domain fibrinogen structure the specific sites of the fibrin assembly in each of the domains were found. COOH-terminal regions of the A alpha-chains play independent part in the fibrinogen and fibrin. That is why it is relevant to consider them as alpha C domains. In the free fibrinogen molecules (in solution) these domains are responsible for globular shape, they are linked to domains D intramolecularly. When fibrin assembly takes place, alpha C-domains play significant carriage role in fibrin molecules interaction, linking to domains D intermolecularly. The model of the fibrinogen molecule structure and the general scheme of the fibrin fibers network formation were proposed. Physico-chemical basics of a biological structure assembly were elucidated using the process of the fibrin self-assembly as an example. Much attention was devoted to the problems of practical medicine. The quantitative methods of fibrinogen, soluble fibrin and active fibrin/fibrinogen fragments estimation in blood plasma were developed. PMID- 11200459 TI - [Mechanism of fibrinolysis and thrombolytic therapy]. AB - The thrombolytic treatment with plasminogen activators, such as physiological tissue-type plasminogen activator (t-PA), suffers from a number of significant limitations. There is a resistance to reperfusion and acute coronary reocclusion. The peculiarity of t-PA and one-chain urokinase treatment is their using in very high doses. Thus the process of thrombolytic therapy is proceeding with a deviation from the fibrinolytic mechanism, which is needs of a little quantity of tissue-type plasminogen activator and provides the physiologic thrombolysis without systemic complication. The estimation of this disaccordance suggests, the possible reasons of these complications. PMID- 11200460 TI - [Plasminogen activation by antiplasminogen monoclonal antibody IV-1C. Properties and mechanism of reaction]. AB - In review the results of investigation of plasminogen(Pg) activation by antiplasminogen monoclonal antibody IV-1c have been presented. Antigenic determinant of IV-1c was localized in Val709-Gly718 site of Pg protease domain. IV-1c completely inhibited the Pg activation by streptokinase, but increased the rate of Pg activation by t-PA and urokinase. Catalytic properties of plasmin in complex with IV-1c were studied. It was found that IV-1c induced catalytic activity in Pg-IV-1c complex. It was shown that Pg and IV-1c interacts in complex by two-centre mechanism: IV-1c binds with Pg by paratope and by N-terminal lysine of gamma-chain and Pg binds to IV-1c by one of the lysine binding sites and by V709-G718 site of protease domain. The influence of pH, temperature, 1.5 mM Ca2+, Mg2+, Sr2+, Ba2+, Co2+, Ni2+ cations and 10 mM Cl-, F-, Ac-, SO4(2-), HPO4(2-) anions on lag and fast phases of Pg activation by VI-1c was investigated. It was revealed that Val709-Gly718 site was determining in Pg activation by IV-1c and streptokinase. PMID- 11200461 TI - [Effect of the mycotoxin zearalenone on the metabolism of membrane phospholipids of rat lymphocytes]. AB - The data obtained have shown that a single intravenous administration of 1 ml of mycotoxin zearalenon alcohol solution (15 mg/ml) to rats leads to the formation of pronounced abnormalities in lymphocyte membranes phospholipid (PL) metabolism. These changes are conditioned by activation of phospholipase A2, which catalyses the deacylation of PL-glycerides predominantly phosphatidylcholines with the formation of high concentrations of lysophosphatidylcholines. On the other hand, intensification of deacylation processes of PL, which accompanied by the liberation of high quantities of unsaturated fatty acids leads to the active incorporation of its into the processes of lipids free radical peroxidation with the formation of significant quantities of lipid peroxides. Intraperitoneal administration of 1 ml 10% sol of sodium thiosulfate no later then 1-2 h after zearalenon toxic action leads to the normalization of disorders observed. PMID- 11200462 TI - [Biologically active substances isolated from Hypericum attenuatum Choisy]. AB - Four dianthrones, two oxymethylanthraquinones, two reductive forms of anthraquinones and five flavonoids have been isolated from the plant source Hypericum attenuatum Choisy (Guttiferae) firstly investigated for these substances contents. Dianthrones pseudohypericin, protohypericin, protopseudohypericin, oxymethylanthraquinones frangulaemodin, frangulin, reductive anthraquinones emodin anthrone, emodin anthranol, and flavonoids quercetin, quercitrin, isoquercitrin, rutin have been identified for the first time. High hyperoside contents in herb of Hypericum attenuatum is established. PMID- 11200463 TI - [Effect of DDT on the interaction of cortisol with glucocorticoid-binding proteins in rat brain]. AB - It was established that DDT is the isosteric inhibitor of cortisol interaction with purified rat brain glucocorticoid-binding proteins. These results were confirmed in the experiments in vivo on Vistar female rats from one generation. PMID- 11200464 TI - [Cytokine profile and fibrinogen level in blood plasma in diabetic foot under the action of heparin]. AB - The investigation displayed in the article was conducted in order of estimating the content of interleukin-1, tumornecrotic factor and fibrinogen in the patients suffering from the I and II type diabetes mellitus complicated by the lower extremity inflammatory-necrotic process. The type II diabetes was shown to have these substances level as higher as the I one, increasing even more at administrating heparin to the patients. The manifestation of hypercoagulative properties of the latter, as it's postulated, is a result of increasing the synthesis of proinflammatory cytokines. PMID- 11200466 TI - [A rapid method for determining the fatty acid composition of lipid A]. AB - Lipid A is the most conservative part of LPS. Its fatty acids composition can serve as an important taxonomic marker of bacteria. The isolation of LPS and studying their chemical composition are difficult and protracted procedure. We propose the rapid method of determining the prevailed fatty acids of lipid A without isolation of LPS from the cell. The essence of the method is in the release of cell from the lipids which are not components of LPS. These lipids, in contrast to the lipid A, are more easily extractable from the cell structures. The fatty acids, which prevailed in the lipid-free cells, are the structural components of lipid A. PMID- 11200465 TI - [Transport and metabolism of vitamin A]. AB - The present paper is a review of up-to-date findings on vitamin A transport from intestines to target-cell and metabolism of this fat-soluble vitamin. The hypotheses of possible enzymes participation in the process of etherification/hydrolysis and oxidation/reduction of vitamin A are discussed. Furthermore, possible roles of cellular retinoid-binding proteins in the process of vitamin A transport and metabolism are reviewed. PMID- 11200467 TI - [Thiamine: a mechanistic model of interaction with protein]. AB - Mechanistic model of thiamine-binding protein functioning which is based on the potential role of prototropic groups and hydrophobic environment around 5-beta hydroxyethyl substituent of ligand has been proposed. As a model the chemical transformations of thiamine and its structural O-acyl substituted analogues in the presence of ferricyanide and phosphatic buffer in pH range 7,2-7,8 were investigated. The oxidation to the thiochrome and thiochrome derivatives is first order in substrate and ferricyanide concentrations. It is found that the reciprocal of the pseudo-first-order rate constant increases in ferrocyanide concentration at the constant oxidant concentration. Rate constants and partition ratios for reaction of thiamine, O-benzoylthiamine, O-(4-nitrobenzoyl)thiamine, O (2-norbornoyl) thiamine, O-(1-norbornoyl)thiamine, O-(1-adamantoyl) thiamine, O (2-adamantoyl) thiamine, O-(5-methyl-1-adamantyl)acetylthiamine, O-(2 adamantyl)acetylthiamine, O-(1-adamantyl)acetylthiamine were determined. The acceleration effect of hydrophobic fragment of O-acyl substituent is attributed to the formation of neutral tricyclic form in the step followed by electron transfer to ferricyanide. Mechanistic implications for possible transformation of thiamine in neutral tricyclic form at interaction with thiamine-binding protein are discussed. PMID- 11200468 TI - ELISA-based method for determining the affinity of bivalent antibodies of two specificities in a mixture. AB - The problem of the evaluation of the affinity for two types of bivalent antibodies in a mixture is considered. It is shown that the binding curve in appropriate coordinates can be used to compose either a system of four equations with four unknowns or a system of two equations with two unknown variables. The numerical solution of these equation systems yields affinity constants for both antibodies and the relationship between concentrations of antibodies studied in the mixture. PMID- 11200469 TI - [Pilot plant and experimental laboratory production. The role in biotechnology industry development]. AB - A stage-phase approach can contribute to unnecessarily long product development time. A simultaneous approach that integrates all development resources through an effectively managed pilot plant can significantly shorten the product development cycle. An intensive development of the domestic biotechnology manufacturing is impossible without creation of the real pilot plant market in Ukraine. PMID- 11200470 TI - [Development of biochemistry in the Biology Department of Kharkhov State University. Formation of a new direction--physiology and biochemistry of aging]. AB - The article presents some data on teaching Biochemistry at the Nature Department of Kharkiv Imperial University Physico-Mathematical Faculty, as well as restoration of biochemical education and scientific researches as a result of the University reorganization in the Soviet period and foundation of the Biochemistry Chair at the Biological Faculty in the renovated Kharkiv State University. The analysis of scientific biochemical investigations conducted in the Kharkiv University till now is revealed. The special attention is paid to development of such a scientific trend as age physiology and biochemistry. The article deals with the comprehensive information on scientific and pedagogical activity of the outstanding scientists such as O. V. Nagorny and I. M. Bulankin as founders of the Kharkiv school of age physiology and biochemistry. The work has utilized some archive data. PMID- 11200472 TI - [Features of fibronectin-dependent activation of ribosomal protein S6 kinase (S6K1 and S6K2)]. AB - Integrin family of adhesion receptors play an important role in organizing the actin cytoskeleton and in signal transduction from the extracellular matrix. The previous studies have shown that exposure of fibroblast cells to extracellular matrix proteins activates ribosomal S6 kinase 1 (S6K1) pathway in a ligand dependent manner. Recently, a new, highly homologous ribosomal S6 kinase, termed S6K2, was identified. It has 70% amino acid identity in the overall sequence with S6K1, and the potential phosphorylation sites of S6K1 are conserved in S6K2. However, the N- and C-terminal domains of S6K2 are quite different from those of S6K1. In this study we have examined dynamics of fibronectin-induced activation of these two kinases, transiently expressed in human HEK 293 cells. Differences between profiles of activation of S6K1 and S6K2 were observed in the early period of fibronectin stimulation. Fibronectin-induced changes in S6K2 activity were closely correlated with phosphorylation at Ser423, which is homologues to Ser 434 of S6K1. Although we didn't observe considerable changes in phosphorylation of S6K1 at Ser434, suggesting potential differences in the regulation of these homologous kinases upon fibronectin stimulation. PMID- 11200471 TI - [Riboflavin biosynthesis in yeast as a model for estimating mechanisms of regulating synthesis of biologically active substances]. AB - General principles of regulation of transcription in eucaryotic cells are characterized. Investigations on riboflavin biosynthesis and regulation of this process in yeasts are summarized. The data obtained permit to consider riboflavin biosynthesis control as an interesting and convenient model capable to estimate the mechanisms various transcription factors action. These investigations are required in order to reveal general features of vitamins and relative compounds biosynthesis regulation. PMID- 11200473 TI - [Intracellular localization and characteristics of monophenol monooxygenase in the leaves of tea plants]. AB - The intracellular localization and some properties of monophenol monooxygenase (MPMO) from fresh tea leaves have been studied. It has been demonstrated that MPMO activity is located in cytosole and chloroplasts. These two forms have different properties. Molecular weights of cytosole and chloroplasts MPMO are 41 and 28 kD respectively. The chloroplasts and cytosole forms of MPMO reveal maximum activity at pH 5.3 and 7.1 respectively. PMID- 11200474 TI - [Accumulation of Ca ions in intracellular structures of rat myometrium during subacute, acute, and chronic administration of ethanol]. AB - The effects of subacute, acute and chronic ethanol exposure on the activity of Ca(2+)-accumulating systems of mitochondria and endoplasmic reticulum in myometrial cells of nonpregnant estrogen-treated rats were studied. It has been shown that the activity of Ca(2+)-accumulating system of mitochondria was higher than the activity of Ca(2+)-accumulating system of endoplasmic reticulum in myometrial cells from control, acute and subacute treated with ethanol rats. Under ethanol chronical assumption both Ca(2+)-accumulation in mitochondria and Ca(2+)-transporting activity of endoplasmic reticulum are inhibited. In the latter ease Mg2+, ATP-dependent Ca(2+)-pump lost its sensitivity to oxytocin. PMID- 11200475 TI - [Antioxidant and biological activity of melatonin]. AB - Neurohormone melatonin controls the circadian rhytmicity of some biological processes, unites the functions of nervous, endocrine and immune systems. Melatonin is a powerful bioantioxidant, capable to be dissolved in water and lipids, runs through membranes and barriers, accumulates in cell nuclei and protects DNA from oxidative stress. Melatonin displays immunomodulating, radioprotective and antitumor activities. PMID- 11200476 TI - [Ca2+-transporting properties of myometrial plasma cell membrane Ca2+, Mg2+ ATPase reconstituted in liposomes]. AB - Purified myometrium cells plasma membrane Ca2+, Mg(2+)-ATPase was reconstitute in liposomes in functionally active state by the method of cholate dialysis: it showed ATP-hydrolase activity increased by 0.8 microM A23187 average 4 times and it showed Mg2+, ATP-dependent Ca(2+)-transporting activity. Reconstituted system transported Ca2+ at an initial rate of 114.4 +/- 16.3 nmol.min-1.mg-1 with the stoichiometry Ca2+: ATP = 1: (3.2-3.7). Calmodulin increased by 30% the initial rate of Ca(2+)-accumulation by the proteoliposomes with reconstituted Ca2+, Mg(2+)-ATPase; 0.1 mM orthovanadate decreased by 80% Ca(2+)-accumulation by this system. Ca2+, Mg(2+)-ATPase reconstituted in liposomes is just Ca(2+) transporting ATPase of the plasma membrane. Obtained enzyme preparate can be utilised for study of the properties of this important energy-dependent Ca(2+) transporting system of smooth muscle cell. PMID- 11200477 TI - [Change in Ca2+ transport in myometrial plasma cell membrane in proton gradient dissipation]. AB - By means of delta pH 14C-methylamine indicator the myometrium vesicle sarcolemma fraction was shown to be capable, while applying a "delta pH-leap", for developing in it a proton transmembrane gradient, dissipating in time. The proton gradient dissipation under Ca ions transmembrane equilibrium concentration is a driving force of these ions transposition against the concentration gradient. The blocking agents of H+ transport--Cd ions and DCCD decrease the proton-dependent 45Ca2+ accumulation in the vesicle sarcolemma fraction. The conclusion has been made about the possibility of Ca2+(H(+)-exchange on the uterus smooth cells sarcolemma. The possible physiological value of this exchange is under discussion. PMID- 11200478 TI - Decomposition of acetylcholine with ethylene formation in vitro. Possible free radical mechanism of acetylcholine action. AB - Experiments were designed to investigate the effect of different buffered solutions, Fenton reagent and hydrogen peroxide on acetylcholine decomposition with ethylene formation. The data of the present study suggests that acetylcholine is decomposed in vitro to form ethylene by interacting with the free radicals or in the Hofmann's splitting reaction. It is found that free radicals are required for the fast decomposition of acetylcholine to form ethylene. A general mechanism to explain the rapid biological effects that can be influenced by the free radicals was proposed. We have concluded that endogenous metabolic free radicals can be involved in the decomposition of acetylcholine as well in the biological activation of formed ethylene in vivo. PMID- 11200479 TI - Human anti-DNA secretory immunglobulins A possess endonuclease activity and they are able to cause the destruction of nuclear chromatin in vitro. AB - sIgA possessing ability to hydrolyse plasmid DNA to linear forms was purified from human milk by sequential chromatography on protein A-sepharose, DEAE Fractogel and DNA-cellulose. It was discovered that incubation of sIgA with nuclei of porcine embryo kidney cells permeabilized by Triton X-100 causes formation of electrophoretically mobile forms of nuclear nucleic acids and inhibition of phosphorylation of nuclear proteins. We suppose that sIgA possessing affinity to DNA and endonuclease activity can cause degradation of cell nuclear chromatin. PMID- 11200480 TI - [Effect of rhenium complexes with organic ligands on acid resistance of human erythrocytes]. AB - The authors showed stabilizing effect of rhenium binuclear cluster compounds with organic ligands on erythrocytic membranes. Estimation of functional condition of cells was studied by a chemical fragility method. Biphase type of rhenium complexes concentration curves stabilization has been found out; the influence of organic radicals and axial substructures (Cl- and Br-) on degree of stabilization has been showed. Different mechanisms of interaction of the investigated complexes with erythrocytic are suggested. PMID- 11200481 TI - [Effect of N-acylethanolamines on adrenal cortex function]. AB - The possibility of NAE to take part in the regulation of the function of adrenal glands was studied. It was shown that two times NAE (18:0) injection in a dose 5 mg/kg of weight increased the content of 11-hydroxysteroids in blood of intact male rats. NAE caused the raise of the blood hormone content by 4 times under the immobilization stress. It is apparent that augment of stress response under the influence of NAE in vivo is explained by the activation of hypophysis-adrenal cortex system. In vitro NAE lowered steroidogenesis by near 40%. One can suggest that this decrease is caused by membranotropic properties of NAE. PMID- 11200482 TI - [Level of group E prostaglandins in gastric mucosa of patients with various forms of chronic gastritis]. AB - There was studied prostaglandins E concentration in bioptats of gastric mucosa in 158 patients with various forms and localization of chronic gastritis using a radioimmunological method. Chronic gastritis without atrophy and with mild atrophy showed to have decreased levels of prostaglandins E in comparison with the control. In the patients with atrophic gastritis with "reconstruction" of epithelium there was revealed an increase of prostaglandins concentration, which was maximal in the patients with atrophic-hyperplastic forms of the disease. PMID- 11200483 TI - [Activity of cytoplasmic proteinases from rat liver in Heren's carcinoma during tumor growth and treatment with medicinal herbs]. AB - The dynamics of the acid and neutral proteinases general enzymes activity change in the hepatocytes postnuclear fraction in the rats suffering from the Heren's carcinoma was investigated. It was determined that in the tumor development of the enzyme activity level of both the acid and neutral proteinases increased 2,6 fold. The natural preparation of the herbs (Calendula officinalis L., Echinacea purpurea L., Scorzonera humilis L., Aconitum moldavicum Hacq.) normalizes both the activity of the investigated enzymes and coefficients of the liver weights of the sick animals. The chemical medicinal preparation 5,6-benzcumarine-5-uracil normalizes the activity of the neutral cytoplasmatic proteinases and reduces the level of the proteolytic activity of the acid enzymes in comparison with the control group of the animals as well as increases of the liver weight coefficients. PMID- 11200484 TI - [Role of xanthine oxidase and xanthine dehydrogenase systems in thymocyte apoptosis, induced by papaverine]. AB - It has been established that papaverine as well as other xenobiotics (dexamethasone and nitrosodimethylamine) [figure: see text] provoked the thymocyte death like apoptosis. The increase of the quantity of double-strand, single-strand DNA breaks and low molecular weight fragments of DNA preceded cell death. In papaverine-induced process of thymocyte apoptosis the total activity of xanthine oxidase in thymocytes strongly elevated long before their death, the conversion of xanthine dehydrogenase (D-form) to xanthinoxidase (O-form) and accumulation of O-form in the cultural medium took place. Direct stimulating effect of papaverine on O-form of enzyme in thymocyte lysate was revealed. The used digitonin thymocytes were divided into cytoplasmic and structural component fractions. It was shown that about 80% of total xanthinoxidase activity was concentrated in cytoplasma while only 20% of its activity was found in structural components. More higher ratio of xanthinoxidase/xanthindehydrogenase (XO/XDH) was observed and papaverine-induced changes of these enzyme forms activities were expressed more brightly in the structural components, than in the thymocyte cytoplasma. During the process of developing thymocytes apoptosis caused by papaverine the reaction of lipid peroxidation was intensified. XO-hypoxanthin system displaying prooxidant influence on cells increased the cytotoxic effect of papaverine but the presence of allopurinol or catalase and superoxidedismutase decreased it. Besides, cytotoxic action on thymocytes of allopurinol itself as well as hypoxanthin itself was revealed. PMID- 11200485 TI - Investigation of stillbirth. AB - The pathologic investigation of stillbirth is often frustrating, and may be viewed as unrewarding, because the reason for death of the infant frequently is not identifiable. This outline attempts to identify an approach to the examination of the stillborn and accompanying placenta, with appropriate use of ancillary studies that may uncover the cause of death and/or identify factors that could prejudice future pregnancies. PMID- 11200486 TI - One-month-old infant with multiple ulcers of stomach, small bowel, large bowel, and protein-losing enteropathy: case report. AB - Multiple inflammatory ulcers of the gastrointestinal tract are rare in young infants. Most cases are caused by infectious organisms, vasculitis, or an autoimmune process. We report a 1-month-old infant who was healthy until he presented with an inflammatory mesenteric cyst, and multiple ulcers of the stomach, duodenum, jejunum, ileum, and colon. Histologically, the ulcerations were sharply demarcated, full thickness, and filled with macrophages. He had a low serum albumin and IgG due to protein-losing enteropathy. He was treated with supportive care and immunomodulating drugs. The gastrointestinal inflammation resolved by 3 and 1/2 years of age. The medications were withdrawn at 5 and 1/2 years of age he had no relapse of clinical symptoms. He continues to have asymptomatic mild hypoalbuminemia and low serum IgG. We could not find a report of a similar clinical presentation and outcome. PMID- 11200487 TI - Comparative immunohistochemical study of insulin-like growth factor II and insulin-like growth factor receptor type 1 in pediatric brain tumors. AB - Insulin-like growth factor (IGF)-II is an important growth factor in development of the central nervous system. The purpose of this study was to evaluate expression of IGF-II and IGF receptor type 1 (IGFR1) in various pediatric brain tumors. Immunohistochemistry for IGF-II and IGFR1 was performed on 15 choroid plexus papillomas (CPPs) including 1 atypical CPP, 2 choroid plexus carcinomas (CPCs), 5 anaplastic ependymomas, 7 nonanaplastic ependymomas (simply referred to as "ependymoma"), 5 medulloblastomas, 1 cerebral neuroblastoma, and 1 atypical teratoid/rhabdoid tumor (ATRT) along with 10 non-neoplastic choroid plexus and 3 non-neoplastic ependymal linings. All non-neoplastic choroid plexus, CPPs, CPCs, anaplastic ependymomas, ATRT, 71% of ependymomas, and 67% of non-neoplastic ependymal linings showed cytoplasmic positivity for IGF-II, whereas all medulloblastomas and the cerebral neuroblastoma were negative for IGF-II. In addition to cytoplasmic positivity for IGFR1, membranous positivity was observed in 73% of CPPs, both CPCs, the ATRT, 22% of non-neoplastic choroid plexus, 80% of anaplastic ependymomas, and 29% of ependymomas, but not in any medulloblastoma, cerebral neuroblastoma, or non-neoplastic ependymal lining. IGF-II and IGFR1 may play roles in the pathogeneses of CPP, CPC, anaplastic ependymoma, ependymoma, and ATRT. Immunohistochemical testing for IGF-II and IGFR1 may be useful in differentiating ATRT, CPC, and anaplastic ependymoma from medulloblastoma and cerebral neuroblastoma. PMID- 11200488 TI - Accidental modification of Attwood's stain on decalcified preparations, yielding improved differentiation between woven and lamellar bone. AB - In an earlier report, a modification of the Attwood's stain was used to study sections of decalcified bone and the procedure aided in the distinction between lamellar and woven bone. Lamellar bone showed preferential affinity for phloxine (red) yet resisted differentiation with tartrazine (yellow), while woven bone stained well with tartrazine. In addition, osteoid seams were identified by their affinity for tartrazine. Differential staining was abolished by pretreatment with periodic acid. Recently, accidental use of potassium permanganate in an acidified medium of pH 1.94, instead of pH 6.44, yielded unexpected results with a much sharper, consistent distinction between woven and lamellar bone. This probably reflects changes in the noncollagenous, interfibrillary matrix proteins of bone, but the exact reason(s) is not known. In our view, this serendipitous modification represents an advance over the previous method, and has allowed us to study the structure of bone in some of the systemic disorders, e.g., osteogenesis imperfecta, with greater ease than before. This method does, however, suffer the disadvantage of interfering with the intensity of the staining of any cartilaginous matrix, and the original application is still of value. PMID- 11200489 TI - Connective tissue growth factor expression in pediatric myofibroblastic tumors. AB - Human connective tissue growth factor (CTGF) is a secreted cysteine-rich peptide and a member of the peptide family that includes serum-induced immediate gene products such as a v-src-induced peptide and a putative proto-oncogene, c-src. CTGF is secreted by endothelial cells, fibroblasts, smooth muscle cells, and myofibroblasts. Its expression is increased in various human and animal fibrotic diseases. We hypothesized that tumors with significant fibrous and vascular components would exhibit increased expression of CTGF. We examined the expression of CTGF mRNA by in situ hybridization in 12 pediatric tumors and tumor-like conditions, including angiofibroma, malignant fibrous histiocytoma, infantile myofibromatosis, and malignant hemangiopericytoma. All the tumors showed moderate to intense CTGF expression in tumor cells and/or endothelial cells of the associated vasculature. Angiofibromas expressed CTGF only in factor VIII-positive endothelial cells and vascular smooth muscle cells. In contrast, infantile myofibromatosis, malignant hemangiopericytomas, and fibrous histiocytomas expressed CTGF in both endothelial cells and in vimentin-positive tumor cells, particularly those around the blood vessels. CTGF mRNA was not detected in the inflammatory cells observed in many of the tumors. The presence of CTGF in the endothelial cells and tumor cells around blood vessels raises the possibility that CTGF is involved in the pathogenesis of these myofibroblastic tumors. PMID- 11200490 TI - Pediatric core needle biopsy: strengths and limitations in evaluation of masses. AB - Needle core biopsies (NCB) are widely used in adults but are less often used for the evaluation of pediatric tumors. To determine the diagnostic utility of NCB for pediatric tumors, we performed a retrospective analysis. Fifty NCB of masses from 1992 to 1998, subsequent pathologic specimens, and medical records were reviewed. All patients were less than 21 years of age. Of the NCB 78% (39/50) were diagnostic of a neoplasm, 8% (4/50) were nondiagnostic in cases where a tumor was subsequently diagnosed, and 14% (7/50) revealed inflammatory or reactive lesions, with no subsequent diagnosis of a neoplasm according to medical record review. In cases in which a neoplasm was present, NCB was diagnostic in 91% (39/43). For cases in which there was a previous diagnosis of a tumor, 100% (9/9) of NCB were diagnostic of a recurrence or metastasis. In cases of NCB for primary tumor diagnosis, 88% (30/34) were diagnostic. The most common problems encountered were related to specimen adequacy, such as insufficient tissue, crush artifact, and tumor necrosis. Tumor diagnoses were as follows: primitive neuroectodermal tumor (PNET)/Ewing sarcoma (12), malignant lymphoma/Hodgkin's disease (8), rhabdomyosarcoma (4), germ cell tumor (3), Wilms' tumor (3), neuroblastoma (1), sarcoma, not otherwise specified (4), and other neoplasms (8). There were no complications of the procedure. NCB of pediatric tumors is an effective diagnostic tool and can be used to obtain diagnostic material quickly and safely. NCB was diagnostic in 90% of cases in this series. When NCB provide sufficient material for immunohistochemical, cytogenetic, flow cytometric, and other ancillary studies, the diagnostic efficacy is enhanced. The major limitations in this series were related to sampling problems and specimen adequacy for comprehensive pathologic evaluation. PMID- 11200491 TI - Morphometric assessment of Hirschsprung's disease: associated hypoganglionosis of the colonic myenteric plexus. AB - At present, there are no generally acceptable criteria for the evaluation of hypoganglionosis of the myenteric plexus. The aim of this morphometrical investigation was to examine the most important quantitative characteristics of hypoganglionosis. Colon specimens from 35 children with Hirschsprung's disease were assessed morphometrically. Twenty specimens with Hirschsprung's disease and proximal hypoganglionosis of the myenteric plexus were compared with 15 specimens with Hirschsprung's disease and normal innervation in the proximal myenteric plexus. All native surgical specimens were caudocranial coiled and sectioned in a cryostat. Nerve cells and ganglia were selectively stained with an enzyme histochemical lactic dehydrogenase reaction. Morphometric measurements were done with an optic-electronic image analysis system. Hirschsprung's disease-associated hypoganglionosis of the myenteric plexus is characterized by a significant decrease in ganglion cross-sectional area (-56.2%) and in plexus area per mm colon (-53.5%). Together with these data, an increase in ganglion distance (+20%) was also determined, and the number of nerve cells per mm colon was decreased by 25.5%. The decrease in ganglion area and in the number of nerve cells per mm colon in the myenteric plexus proved to be the most characteristic parameters of a hypoganglionosis. PMID- 11200492 TI - Telomerase activity as a prognostic factor in neuroblastomas. AB - Neuroblastoma is the most common extracranial solid tumor of early childhood. This tumor demonstrates significant heterogeneity with respect to pathologic, genetic, and clinical features. The outcome varies from spontaneous regression or maturation to rapid progression, despite aggressive therapy. Prognostic factors have been found that identify those tumors which have a high probability of aggressive behavior; these factors include unfavorable histology, MYCN copy number, deletions of the short arm of chromosome 1, DNA content, and TRK-A (high affinity receptor protein for nerve growth factor) expression. Recent studies have suggested that high levels of telomerase activity also correlate with poor clinical outcome. We investigated this relationship in 40 patients with untreated neuroblastoma, using a PCR-ELISA assay for telomerase activity. In these patients, 23 tumors had no or minimal telomerase activity whereas 15 had high levels of activity. In two tumors, telomerase activity was not assessable. There was significant correlation between the telomerase activity and MYCN copy number, 1p deletions, and TRK-A expression, as well as patient age, clinical stage, and outcome. The histological classification of the tumors was not significantly different between the two groups, being predominantly unfavorable by the Shimada classification. In addition, for 17 patients tumor tissue was assessed for telomerase activity post-chemotherapy. In those cases where the tumor was negative for telomerase activity before and after chemotherapy, the patients uniformly did well. In cases where the tumor was positive before and negative or weakly positive after treatment, two of the seven patients did well clinically. However, in cases that were positive after chemotherapy, all had recurrence or died. In conclusion, telomerase activity appears to be a prognostic factor for neuroblastomas. In addition, assessment of tumors post-chemotherapy may be a further indicator of clinical outcome. PMID- 11200493 TI - Human papillomavirus-11-associated recurrent respiratory papillomatosis is more aggressive than human papillomavirus-6-associated disease. AB - The aim of this study was to determine whether viral type (HPV-6 vs. HPV-11) could predict the clinical course of recurrent respiratory papillomatosis in children. Viral typing, using the polymerase chain reaction, was performed on laryngeal biopsies of 61 patients treated at Children's Hospital of Michigan. HPV 6 was detected in 29 of the patients' biopsies and HPV-11 in 32 biopsies. HPV-11 was more common among the African-American patients than among Caucasians (P = 0.001). Patients with HPV-11 were diagnosed at a younger age (36.2 vs. 48.2 months; P = 0.04) and were more likely to have active disease (P = 0.0311) at the time of this study. They tended to have longer periods of disease activity (8 years vs. 5 years; P = 0.026), required more surgical procedures (42 procedures/patient vs. 13.6; P = 0.02), and more procedures per patient, per year (2.9 vs. 5.3; P = 0.0164). Three of the patients infected with HPV-11 developed invasive papillomatosis and bronchogenic squamous cell carcinoma, and two of these patients died of disease. Our findings suggest that HPV-11 infection confers a more aggressive course to recurrent respiratory papillomatosis. PMID- 11200494 TI - Malignant melanoma in children and congenital melanocytic nevi: DNA content and cell cycle analysis by flow cytometry. AB - Malignant melanoma (MM) in children, although a rare neoplasm, can occur within a preexisting congenital melanocytic nevus (CMN). All the potential risk factors for this phenomenon are not well known, but increases in S phase and G2 + M phase of cell cycle, DNA aneuploidy, and cell cycle abnormalities in precursor lesions might be among the risk factors. Using paraffin-embedded tissue, we performed a retrospective analysis of DNA content, aneuploidy, and cell cycle by flow cytometry. Two groups of patients were analyzed: 28 children with CMN who did not developed MM, and 6 patients who further developed MM. In this second group, three patients had four biopsies done before the appearance of MM and in two patients biopsies were done after the appearance of MM. All CMN not associated with MM exhibited diploid cells only, their S phase was 11.5% (+/- 3.8), and their G2 + M phase was 2.5% (+/- 2.2). Among those patients who developed MM, 3/6 had an S phase > 15.5 and a G2 + M phase > 2.3 prior to the appearance of MM. Two out of six patients had a tetraploid DNA when MM developed and died with a disseminated MM. They had an S phase > 15.5 and their G2 + M phase was > 2.5. We propose that evaluation of DNA content and cell cycle by flow cytometry is a useful method to supplement biopsy findings in children with CMN who have lesions suspicious of developing a MM. PMID- 11200495 TI - Comparison of immunohistochemistry and silver stain for the diagnosis of pediatric Helicobacter pylori infection in urease-negative gastric biopsies. AB - We compared immunohistochemical and silver stains of pediatric gastric biopsy sections for the identification of Helicobacter pylori infection with chronic inflammation and a negative urease screening test. Thirty-seven patients (age range 10 months to 21 years) whose gastric antral biopsies were negative for the rapid urease test (CLO(R)) but positive for lymphocytic infiltration were selected for a retrospective study. Specimens had been subjected to a rapid urease test (CLO(R)) and hematoxylin and eosin staining, and Dieterle silver staining and immunohistochemical staining specific for H. pylori were also performed. Twelve additional patients with urease-positive biopsies were used as controls. With Dieterle staining, 8/37 (22%) urease-negative biopsies contained organisms morphologically compatible with H. pylori, 21/37 (56%) contained organisms not compatible with H. pylori, and 8/37 (22%) were negative for organisms. Immunostaining confirmed 6/8 (75%) Dieterle-positive cases as being H. pylori, was negative in 2/8 (25%) Dieterle-positive cases, and was positive in 2/8 (25%) Dieterle-negative cases. Biopsies from 8/12 (67%) urease-positive specimens contained organisms seen with both Dieterle and immunohistochemical stains, and 4/12 (33%) were negative with both stains. Although both stains yielded comparable results with H. pylori-positive biopsies, Dieterle staining was potentially confusing because of nonspecific staining of other organisms. A significant proportion of (CLO(R))-negative biopsies was positive for H. pylori with special stains. We therefore recommend the use of immunohistochemical staining rather than silver staining in the evaluation of urease-negative gastric biopsies demonstrating chronic inflammation in children. PMID- 11200496 TI - Ectopic cerebellum presenting as a suprasellar mass in infancy: implications for cerebellar development. AB - A 4-month-old infant with a history of nasopharyngeal teratoma developed progressive optic neuropathy. Neuroimaging studies demonstrated a solid, isointense, suprasellar mass impinging on optic nerves and chiasm superiorly. The mass was subtotally resected. No attachment of the mass to brain stem or cerebellar structures was noted. Histological examination identified the tissue as developing cerebellum. The cytoarchitecture and cellular constituents of the cerebellar tissue were only slightly distorted. All cerebellar cortical constituents were arranged anatomically, and an external granular cell layer was present superficially. The latter was actively proliferating and appropriately cellular for the infant's age. The clinical presentation of ectopic cerebellum as a suprasellar mass in an infant is highly unusual. Moreover, this example illustrates the ability of cerebellar tissue to mature appropriately in a site distant from the posterior fossa, removed from ascending and descending afferent projections. Intrinsic signaling mechanisms appear sufficient to direct histogenesis in developing cerebellar cortex. PMID- 11200497 TI - Large granular lymphocyte leukemia: case report of chronic neutropenia and rheumatoid arthritis-like symptoms in a child. AB - Lymphoproliferative disorders of large granular lymphocytes (LGL) are heterogeneous, with a clinical/pathologic spectrum ranging from a benign polyclonal expansion to an aggressive clonal disease. Often these lymphoproliferative disorders are associated with autoimmune disease. The clonal form of the disorder, LGL leukemia, typically occurs in older adults with a median age of 55 years at diagnosis. Pediatric cases are referred to in review articles; however, no detailed reports of T-cell LGL leukemia in children exist. This report illustrates a case of a child who presented initially at age 2 and 1/2 years with psoriasis, juvenile rheumatoid arthritis-like symptoms, and neutropenia. Bone marrow examinations obtained throughout his course have demonstrated progressive hypercellularity with increased reticulin fibers and replacement of the normal marrow elements by lymphocytes, which were later identified as large granular lymphocytes. Further testing with immunophenotyping by flow cytometry and T-cell receptor gene rearrangement studies revealed a monoclonal proliferation of large granular lymphocytes and confirmed a diagnosis of LGL leukemia. Although rare, large granular lymphocyte leukemia should be included in the differential diagnosis of chronic neutropenia in children. PMID- 11200498 TI - Representative CGH (comparative genomic hybridization) image of an esophageal squamous cell carcinoma cell line, KYSE150, exhibiting marked amplifications at 1q32 and 9p23-24. PMID- 11200499 TI - Naturally occurring and synthetic inhibitors of NF-kappaB functions. AB - Nuclear factor (NF)-kappaB is a transcription factor that induces the immunoglobulin kappa chain, cytokines such as interleukin (IL)-1, IL-2, IL-6, IL 8, tumor necrosis factor (TNF)-alpha and interferon gamma, and cell adhesion proteins. It also induces anti-apoptotic proteins, and inhibits TNF-alpha and anticancer drug-induced apoptosis. Therefore, NF-kappaB function inhibitors may be useful as anti-inflammatory and anticancer agents. Microbial products such as panepoxydone, cycloepoxydon and gliotoxin are known to inhibit activation of NF kappaB. We have designed and synthesized new NF-kappaB inhibitors from the structure of an antibiotic, epoxyquinomicin C. The designed compound, DHM2EQ, inhibited TNF-alpha-induced activation of NF-kappaB and showed a therapeutic effect in mouse rheumatoid arthritis model. PMID- 11200501 TI - The 9-position in berberine analogs is an important determinant of DNA topoisomerase II inhibition. AB - A current model suggests that the intercalative and minor groove binding components of protoberberines and related compounds are important for DNA topoisomerase I and/or II inhibition. The significance of the 9-substituent in berberine on drug-topoisomerase II interactions is reported here and is based on a comparison of 9-ethoxycarbonyl berberine (compound 1), 9-N,N-dimethylcarbamoyl berberine (compound 2) and 12-bromo berberine (methoxy group at 9-position; compound 3) as enzyme inhibitors. Compound 1 selectively inhibited topoisomerase II and stabilized cleavage complexes predominantly at unique sites and some background sites (depending on the concentration). This agent also allowed partial dissociation of enzyme from the DNA in the absence of religation, indicating unique interactions between 1, enzyme and DNA in the ternary complexes. Compound 2, which had similar DNA binding properties to 1, was not a topoisomerase II poison in the tested concentration range. In contrast, compound 3 was a stronger DNA binding agent but a much weaker enzyme poison both in vitro and in cell-based assays. The results show that the proposed drug domain for DNA intercalation is not a major determinant of enzyme inhibition for simple berberine analogs. Rather, the 9-substituent within the domain has a major influence, presumably by facilitating drug interaction with enzyme and/or enzyme DNA complexes. PMID- 11200500 TI - Role of DNA minor groove alkylation and DNA cross-linking in the cytotoxicity of polybenzamide mustards. AB - Interstrand DNA cross-links have been considered essential to the activity of current clinical DNA-alkylating antitumour drugs, which generally alkylate in the major groove. However, the relationship between cross-linking adducts located in the minor groove of DNA with cytotoxicity and antitumour activity has not been extensively investigated. Previous studies have shown that cross-linking ability is not correlated with cytotoxicity in a novel series of polybenzamide-linked nitrogen mustard compounds which alkylate DNA at adenines in the minor groove. In the present study the nature of these cross-linking adducts was explored for a related pair of compounds which are both highly effective cross-linkers but which differ in antitumour potential. Both of these drugs effectively interact with adenines in the minor groove, although their sequence specificity differs. However, the cross-linking event was not inhibited by pre-treatment with Hoechst 33258, although this pre-treatment effectively prevented adenine alkylation. The primary cross-links detected may thus represent guanine N7 alkylations in the major groove. Whether minor groove cross-linking adducts can be formed is uncertain, since the effect of background guanine N7 alkylation may complicate analysis. The cytotoxicity of the polybenzamides may therefore be related to other factors such as their interaction with cellular repair systems. PMID- 11200502 TI - Design, synthesis and antitumor cytotoxicity of novel bis-benzimidazoles. AB - A series of novel bis-benzimidazoles, IIa-e, IIIa-e and IVa-g, was designed, synthesized and evaluated for anticancer properties. Certain additional analogs were also designed by introducing the p-quinone moiety, a characteristic feature found in mitomycin C, indolequinones and other examples of bioreductively activated alkylating agents. Structural changes of the bis-benzimidazole nucleus with various leaving groups were investigated for their effects on their pharmacological properties. These compounds were evaluated for their cytotoxicity against human cancer cell lines. The results of the studies indicate that the compounds IIa, IIc, IVa, IVc, IVd and IVg possess significant cytotoxic activities against 22 cell lines in seven cancer panels with GI50 values between <0.01 and 99.5 microM especially in the cases of renal cancer, CNS cancer, colon cancer, melanoma and breast cancer. PMID- 11200503 TI - The influence of lipophilicity on binding of boronated DNA-intercalating compounds in human glioma spheroids. AB - Five boronated DNA-intercalating compounds [5-ortho-carboranyl phenanthridinium (5-o-CP), 5-para-carboranyl phenanthridinium (5-p-CP), 6-para-carboranyl phenanthridinium, water-soluble boronated phenanthridinium and water-soluble boronated acridine (WSA1)], primarily developed for boron neutron capture therapy (BNCT), were analysed regarding their binding in cultured human malignant glioma spheroids. Comparisons were made with the corresponding DNA intercalators ethidium bromide and acridine orange. Octanol/phosphate buffered saline-water coefficients were determined for all compounds, and it was found that the most lipophilic (5-o-CP and 5-p-CP) were most toxic and accumulated high amounts of boron in monolayer cells. These compounds bound primarily in the outermost part of spheroids with poor penetration into the inner region, even after 2 days of continuous exposure. On the other hand, the most hydrophilic compound (WSA1) showed lower toxicity and lower boron accumulation in monolayer cells, and rapid binding in the inner region of spheroids. A reasonable explanation for this observation is that the lipophilic compounds interact mainly with lipophilic parts of the cells, like cellular membranes, and therefore rapidly binds to cells, preventing penetration and binding to cells in the deeper region of the spheroids. The possibility of using these compounds for BNCT are discussed. PMID- 11200504 TI - New potential photodynamic therapeutic anti-cancer agents: synthesis and characterization of demethoxy amino-substituted hypocrellins. AB - A novel method was used to obtain demethoxy amino-substituted hypocrellin derivatives. The reaction condition was mild and amino substitution occurred at position 2 or 11 of hypocrellins with high yield. The photophysical and photochemical properties of the amino-substituted hypocrellins derivatives were investigated, and their significantly enhanced red absorptivities and strong active oxygen-generating functions qualified them as promising photodynamic therapeutic anti-cancer agents. PMID- 11200505 TI - Synthesis and antimelanoma activity of analogues of N-acetyl-4-S cysteaminylphenol. AB - N-Acetyl-4-S-cysteaminylphenol (1) has been shown by Jimbow and co-workers to possess useful antimelanoma activity. It is an analogue of a biosynthetic intermediate in the pathway to melanin and probably acts as a prodrug, being oxidized to an o-quinone which reacts with essential enzymes containing sulphydryl groups resulting in interference with cell growth and proliferation. We have synthesized a range of analogues of 1 by varying the acyl portion of the amide with the intention of increasing the lipophilicity of the compounds. A modest increase in melanoma activity against six melanoma cell lines for these analogues could be correlated with increased lipophilicity. The most active of these compounds, N-[2-[(4-hydroxyphenyl)thiol]ethyl]cyclohexanecarboxamide (9), showed promising selectivity (lack of cytotoxicity) on the non-melanotic cell line SK-Mel-24 and on an ovarian cell line. A significant improvement in antimelanoma activity was observed with a new type of analogue containing three carbon atoms between the sulphur and nitrogen. The most active of these new analogues, N-[3-[(4-hydroxyphenyl)-thiolpropyl]-1-cyclohexanecarboxamide (15), had activity comparable to cisplatin against several cell lines and low cytotoxicity towards the non-melanotic cell line. PMID- 11200506 TI - Tetramethylpiperidine-substitution increases the antitumor activity of the riminophenazines for an acquired multidrug-resistant cell line. AB - The multidrug resistance (MDR)-neutralizing and cytotoxic properties of five tetramethylpiperidine (TMP)-substituted phenazines were compared with those of their corresponding isopropyl-substituted analogues using a P-glycoprotein (P-gp) expressing small cell lung cancer cell line (H69/LX4). All of the TMP-substituted phenazines tested outperformed their isopropyl analogues with respect to both cytotoxic and chemosensitizing properties, indicating the importance of TMP substitution when designing novel riminophenazines with increased activity against MDR cancer cell lines. Of the TMP-substituted phenazines tested, B4112, chlorinated at position 3 of the phenyl- and anilino-rings, had the most potent anti-cancer activity in vitro, making this agent a potential candidate for evaluation in experimental and clinical oncology. PMID- 11200507 TI - ["Minor" traumatology in primary care?]. PMID- 11200508 TI - [Evaluation of extrinsic sleep disorders in a population in Valladolid]. AB - OBJECTIVES: To study the prevalence of external sleep disturbances and their influence in sleep quality. DESIGN: Transversal descriptive study based on personal self-applied interview and the application of the Pittsburg Sleep Quality Index (PSQI) in 1053 persons selected among the over 18 year old population of the city of Valladolid between September 1997 and August 1998 in relation to different sociodemographics variables, life habits and psychiatric pathologies (anxiety and depression evaluated by Golberg Scale). RESULTS: Worsening of life quality and sleep efficiency was significantly associated to external disturbances such as coughing, going to the bathroom and nocturnal awakening and, less significantly, to pain sensation, having nightmares, dysthermic sensations and difficulty to breathing. Sleep external disturbances did not affect daytime activity but was associated to an increased hypnotic drug taking. INTERPRETATION: Sleep external disturbances are one of the most relevant and unknown variables associated to a decrease in sleep quality and, consequently, in life quality. PMID- 11200509 TI - [Process indicators and result indicators in the control of arterial hypertension]. AB - OBJECTIVE: To find whether better compliance with the indicators of procedure of a hypertension monitoring programme guarantees better control in the final blood pressure figures. DESIGN: Descriptive cross-sectional study. SETTING: Gotic Area Health Centre, Barcelona. PATIENTS: Annual audit through random sampling of the computerised records of all the hypertense patients attended at the centre in each of 5 years (1992, n = 337; 1993, n = 318; 1994, n = 322; 1995, n = 325; 1996, n = 325). RESULTS: 1. Procedure indicators: complete physical examination took place in 1996 in only 12% of cases, proportion similar to at the start of the development of the programme (12.2%). Completion of at least two of the three records of protocols (complete physical examination, ECG and analysis) dropped during the period and did not cover half the patients. Screening of the various cardiovascular risk factors (CRF) increased markedly in the 1992-1995 period. 2. RESULTS INDICATORS: The proportion of patients under 66 with SP and DP < 140 and 99 mmHg went up from 23.2% in 1992 to 45.2% in 1996. In the over-65 age-group, it went from 58.9% in 1992 to 81.2% in 1996. CONCLUSIONS: The procedure indicators are still useful, in that they are necessary for designing a new hypertension programme. However, we must not forget that any health programme is designed in order to achieve good control and population impact (survival) results. The procedure is only an aid to reach these aims. PMID- 11200510 TI - [Metabolic control of diabetes mellitus en relation to the quality of the medical records]. AB - OBJECTIVE: To investigate whether there is a relationship between the quality of the clinical history (CH) in primary care and metabolic control of patients with diabetes (DM). DESIGN: Retrospective and observational. SETTING: 15 health centres in the Segovia Area. PATIENTS: 315 diabetic patients, selected at random from among those with a record of the type of DM, date and outcome of at least one HbA1c and treatment at the time of the most recent HbA1c. RESULTS: The quality of the clinical histories was measured through the mean of recording of the following items in the 13 months previous to the most recent HbA1c: weight and height, peripheral pulses, sensitivity, foot examination, creatinine, proteinuria, microalbuminuria, glucaemia levels, back of eye, ECG, and diet, tobacco and alcohol counselling. Other variables that could condition the HbA1c, chronic pathologies and those related to DM, were gathered too. Of patients treated with diet or oral diabetic drugs, patients with a clinical history of < or = 49% quality had a mean HbA1c of 7.40%, whereas those with CH of > or = 50% quality had an average of 6.94% (0.46 difference; 95% CI, 0.03-0.90; p = 0.038). This drop was not attributable to age, gender, years of evolution or BMI differences. The risk of having an HbA1c > or = 7.5% is double in patients with a CH of < or = 49% quality than in those with CH of > or = 50% quality (OR = 2.06; 95% CI, 1.14-3.72). In insulin-treated patients, no association between CH quality and HbA1c was found. CONCLUSIONS: Follow-up of the recommendations for clinical action is associated with better metabolic control in diabetics treated with diet--oral diabetic drugs. This association was not found in insulin-treated patients. PMID- 11200511 TI - [Incidence of amputaciones of the lower extremities in the population with diabetes mellitus in Malaga (1996-1997)]. AB - OBJECTIVE: To find the frequency of amputations of lower limbs (ALL) with the aim of designing a programme to prevent ALL in people with diabetes mellitus (DM). DESIGN: Retrospective observation study. SETTING: Population study in Malaga and its province. PATIENTS: The clinical records of everyone with ALL in public or subsidized hospitals in the province of Malaga between January 1 1996 and December 31 1997 were reviewed. Traumatic or tumoural ALL were excluded. Cumulative incidence, relative risk (RR) of ALL and the mortality rate of people with DM were calculated. RESULTS: 449 ALL took place during the period studied, 316 (70.3%) in people with DM and 133 (29.6%) in people not suffering DM. The incidence of ALL per 100,000 people and per year was 6.3 (CI: 4.7-7.8) in the population without DM and 136.1 (CI: 114.9-157.3) in people with DM. The RR of ALL was 21.6 (CI: 17.6-26.4) for the population with DM, with differences between men and women (16.8 vs. 36.1, respectively). Mean age of ALL was significantly greater (p < 0.05) for the population with DM (70.0 +/- 10.2 vs. 68.9 +/- 15.9 years old). Older ALL were more numerous in both women and men in the two groups studied. The mortality rate, complications and mean stay in hospital were greater in the population with DM. CONCLUSIONS: This study confirmed the greater risk of ALL run by people with DM. The incidence of ALL in this study was less than in countries of Northern Europe, the USA and Australia, but more than in any study published before in Spain. PMID- 11200512 TI - [Evaluation of the quality of communication between levels of care through the inter-consultation document]. AB - OBJECTIVES: To evaluate the quality and improvement of compliance in the inter consultation documents of the primary care team (PCT). DESIGN: Entire care cycle. SETTING: Primary care (PC). MEASUREMENTS: Dimension studied: scientific-technical quality. SUBJECTS: all the inter-consultation documents (ID-1) sent by PC doctors from Irun Health Centre to specialist clinics over a 15-day period. 223 ID-1 for evaluation in April 1998, and 287 for re-evaluation in October 1998. Type of evaluation: retrospective. SOURCE OF DATA: inter-consultation documents and clinical records. CRITERIA: explicit and standard. Corrective measures: educational (discussion of results in meeting of the PCT). RESULTS: A statistically significant improvement was found at the re-evaluation: basic personal details (91.5%-96.8%), legibility (86%-92.7%), medical history and/or customary medication (35.9%-50%) and symptoms (77.8%-87.2%). Good quality levels rose from 20.6% to 42.5%; and bad quality levels fell from 40.8% to 33.4%. 22.2% of our referrals received a reply. 34% of the lack of replies was because of no report from the specialist, 47.8% were attributed to the patient or circuit, and 18% of the patients were awaiting test results. CONCLUSIONS: The information supplied in the ID-1 improved significantly after the quality cycle. Knowing our habitual working practice can serve to stimulate improvement. The criteria we complied with least were: reference to personal antecedents and/or habitual medication, physical examination, and therapeutic measures employed. There was a huge loss of information in the replies to our referrals. PMID- 11200513 TI - [Leisure-free time activities and walking outside their homes among the elderly in the province of Guadalajara]. AB - OBJECTIVE: To find out what elderly people in the province of Guadalajara do in their leisure/free time and daily walking, in the supposition that these can be improved. DESIGN: This was a descriptive, crossover study based on a population group. SETTING: At community level, in the primary care context. PARTICIPANTS: People over 65 without cognitive deterioration and resident in the community, selected at random on the basis of population data bases. The sample finally studied was made up of 192 men and 196 women from the country-side, and 172 men and 220 women from an urban background. INTERVENTIONS: Everyone was interviewed at home or the health centre according to their preferences through a questionnaire, which had undergone a stability study of the replies beforehand through the kappa test-retest coefficient. We screened cognitive deterioration through the Pfeiffer test. MAIN RESULTS: In the country, 43.6% of elderly people (CI: 38.6-48.7) walked under half an hour a day; in the urban context, 34.4% (CI: 29.8-39.4) did so. 24.7% of men (CI: 20.4-29.6) did so; and 51.4% of women (CI: 46.5-56.3). The differences were significant in the two cases. 12.1% (CI: 9.1 15.9) of elderly people in the country had no hobbies, and 9.4% (CI: 6.8-12.9) in the town. Among men and women, this broke down as 11.3% (CI: 8.3-15.1) and 10.1% (CI: 7.5-13.5). respectively. There were no significant differences. CONCLUSIONS: Leisure and free time activities among people over 65 in the province of Guadalajara must be fostered; but above all a daily walk for over half an hour must be encouraged. PMID- 11200514 TI - [Use of the rapid appraisal method for the identification of perceived needs in a low-class barrio in the city of Buenos Aires]. AB - OBJECTIVE: To present rapid appraisal as a qualitative technique for researching the perceived needs of a population, which is valid, rapid and cheap. DESIGN: Qualitative method: semi-structured interviews with key informants, focus group. SETTING: A poor quarter with 2921 inhabitants in the city of Buenos Aires. PARTICIPANTS: Key informants: people resident in the area for over 10 years. MEASUREMENTS AND MAIN RESULTS: The main problems perceived by the community were: environmental pollution because of the accumulation of rubbish, alcohol and drug abuse among the young, and the need to extend the opening hours of the area's health centre. CONCLUSIONS: The needs perceived surpassed specific medical problems. They covered social questions, environmental problems and how to organise the health care system. PMID- 11200515 TI - [Smoking cessation from the community pharmacy]. AB - OBJECTIVES: To evaluate the effectiveness of the intervention of the community pharmacist in a smoking-cessation program. DESIGN: A descriptive prospective study. SETTING: Two pharmacies of the Community of Madrid. PARTICIPANTS: 77 patients who wanted to participate in the smoking-cessation program. The middle age of the participants were 41.6 +/- 10.8; 51.9% were male and 42.8% female. MEASUREMENTS AND MAIN RESULTS: The quit rates of the smoking-cessation program were: 1st. month 80.5%; 3rd. month 54.5%; 6th month 45.5% and 1st. year 42.8%. The patient who use the nicotine treatment at least two months, have more probability to quit smoking successfully (p < 0.05). CONCLUSIONS: The community pharmacy could be a good place to help people to give up smoking. Results of this study show that pharmacists who counsel patients in an intensive smoking cessation program can improve outcomes. PMID- 11200516 TI - [The quality of sleep associated with polypharmacy]. AB - OBJECTIVE: Study of the association between multiple medication and the quality of sleep. DESIGN: Observational, cross-sectional study through two-stage sampling of 1053 people with a questionnaire and application of the Pittsburgh Sleep Quality Interview (PSQI). SETTING: Primary care. Population covered by health centres in the province of Valladolid. POPULATION: Adults over 18 who attended health centres in Valladolid province. RESULTS: As consumption of multiple drugs rose, there was significant deterioration in the overall quality of sleep and each of the following components: subjective quality, latency of sleep, duration of sleep, extrinsic disturbances and consumption of sleeping draughts. No differences were found for day-time repercussions. When psychiatric drug consumption was excluded from the study (to avoid the risk of bias in psychiatric illnesses), deterioration in the quality of sleep, on adding up the remaining therapeutic groups of drugs, was still found. CONCLUSIONS: The fact of consuming multiple drugs chronically may condition a deterioration in sleep quality, which will stimulate us to combat this symptom with more drugs and so further aggravate the problem. New prospective studies need to be undertaken to find out the reasons. PMID- 11200518 TI - [Epilepsy and psychiatry]. PMID- 11200517 TI - [Is it legitimate the use of placebos in primary care?]. PMID- 11200519 TI - [HIV: a task still pending]. PMID- 11200520 TI - [Use and abuse of the prescription of anti-ulcer agents]. PMID- 11200521 TI - [Pharmacy offices]. PMID- 11200522 TI - [Primary care in mental health]. PMID- 11200523 TI - Conformational dynamics in mixed alpha/beta-oligonucleotides containing polarity reversals: a molecular dynamics study using time-averaged restraints. AB - Nucleic acid duplexes featuring a single alpha-anomeric thymidine inserted into each DNA strand via 3'-3' and 5'-5' phosphodiester linkages exhibit local conformational dynamics that are not adequately depicted by conventional restrained molecular dynamics (rMD) methods. We have used molecular dynamics with time-averaged NMR restraints (MDtar) to explore its applicability to describing the conformational dynamics of two alpha-containing duplexes--d(GCGAAT-3'-3' alphaT-5'-5'-CGC)2 and d(ATGG-3'-3'-alphaT-5'-5'-GCTC) x r(gagcaccau). In contrast to rMD, enforcing NOE-based distance restraints over a period of time in MDtar rather than instantaneously results in better agreement with the experimental NOE and J-data. This conclusion is based on the dramatic decreases in average distance and coupling constant violations (delta d(av), J(rms), and delta J(av)) and improvements in sixth-root R-factors (R(X)). In both duplexes, the deoxyribose ring puckering behavior predicted independently by pseudorotation analysis is portrayed remarkably well using this approach compared to rMD. This indicates that the local dynamic behavior is encoded within the NOE data, although this is not obvious from the local R(X) values. In both systems, the backbone torsion angles comprising the 3'-3' linkage as well as the (high S-) sugars of the alpha-nucleotide and preceding residue (alpha - 1) are relatively static, while the conformations of the 5'-5' linkage and the sugar in the neighboring beta-nucleotide (alpha + 1) show enhanced flexibility. To reduce the large ensembles generated by MDtar to more manageable clusters we utilized the PDQPRO program. The resulting PDQPRO clusters (in both cases, 13 structures and associated probabilities extracted from a pool of 300 structures) adequately represent the structural and dynamic characteristics predicted by the experimental data. PMID- 11200524 TI - Solution NMR of proteins within polyacrylamide gels: diffusional properties and residual alignment by mechanical stress or embedding of oriented purple membranes. AB - The diffusive properties of biomacromolecules within the aqueous phase of polyacrylamide gels are described. High quality NMR spectra can be obtained under such conditions. As compared to water, a fivefold reduction in the translational diffusion constant, but only a 1.6-fold decrease (1.4-fold increase) in amide-15N T2 (T1) are observed for human ubiquitin within a 10% acrylamide gel. Weak alignment of the solute macromolecules can be achieved within such gels by vertical or radial compression or by the embedding of magnetically oriented purple membrane fragments. The methods are applied to deriveresidual dipolar couplings for human HIV-1 Nef and ubiquitin. PMID- 11200525 TI - De novo protein structure determination using sparse NMR data. AB - We describe a method for generating moderate to high-resolution protein structures using limited NMR data combined with the ab initio protein structure prediction method Rosetta. Peptide fragments are selected from proteins of known structure based on sequence similarity and consistency with chemical shift and NOE data. Models are built from these fragments by minimizing an energy function that favors hydrophobic burial, strand pairing, and satisfaction of NOE constraints. Models generated using this procedure with approximately 1 NOE constraint per residue are in some cases closer to the corresponding X-ray structures than the published NMR solution structures. The method requires only the sparse constraints available during initial stages of NMR structure determination, and thus holds promise for increasing the speed with which protein solution structures can be determined. PMID- 11200526 TI - Identification of the ubiquitin interfacial residues in a ubiquitin-E2 covalent complex. AB - One of the key intermediates formed during the protein ubiquitination cycle is a covalent complex between ubiquitin (Ub) and the conjugation enzyme, UBC1. In order to probe the interface between these two proteins we have formed the covalent complex in situ (in the NMR tube) using Ub, the catalytic domain of UBC1, UBC1 delta450, an activation enzyme, E1, and Mg2+-ATP. The size of the Ub UBC1 delta450 complex (25 kDa) and its relatively short lifetime (approximately 4 h) makes assignment of the backbone resonances in the covalent species difficult. In order to monitor the formation and identify the interface in the complex we have used fast 1H-15N HSQC spectra to monitor the decay of 1H-15N correlations as a function of time until the complex formed reached about 90%. The residual peak intensities were used to probe the surface of interaction between Ub and UBC1 delta450 and provided a clear surface of interaction on Ub. PMID- 11200527 TI - Ansig for Windows: an interactive computer program for semiautomatic assignment of protein NMR spectra. AB - Assignment of NMR spectra is a prerequisite for structure determination of proteins using NMR. The time spent on the assignment is comparatively long compared to that spent on other parts in the protein structure determination process, but it can be shortened by using either interactive or fully automated computer programs. To benefit from the advantages of both types of program we have developed a version of the interactive assignment program ANSIG to include automatized, yet user-supervised, routines. The new program includes tools for (i) semiautomatic sequential assignment, (ii) plotting of distances from PDB structure files directly in NMR spectra and (iii) statistical analysis of distance restraint violations with the possibility to directly zoom to violated NOEs in NOESY spectra. PMID- 11200528 TI - HNCAN pulse sequences for sequential backbone resonance assignment across proline residues in perdeuterated proteins. AB - A TROSY-based triple-resonance pulse scheme is described which correlates backbone 1H and 15N chemical shifts of an amino acid residue with the 15N chemical shifts of both the sequentially preceding and following residues. The sequence employs 1J(NC alpha) and 2J(NC alpha) couplings in two sequential magnetization transfer steps in an 'out-and-back' manner. As a result, N,N connectivities are obtained irrespective of whether the neighbouring amide nitrogens are protonated or not, which makes the experiment suitable for the assignment of proline resonances. Two different three-dimensional variants of the pulse sequence are presented which differ in sensitivity and resolution to be achieved in one of the nitrogen dimensions. The new method is demonstrated with two uniformly 2H/13C/15N-labelled proteins in the 30-kDa range. PMID- 11200529 TI - Lanthanide induced residual dipolar couplings for the conformational investigation of peripheral 15NH2 moieties. AB - The Ca2 calbindin protein in which one calcium has been substituted with Ce(III), Yb(III) and Dy(III) displays substantial alignment in high magnetic fields due to the high anisotropy of the metal magnetic susceptibility. This property has allowed the measurement of residual dipolar coupling contributions to 1J(HN) and 2J(HH) couplings of asparagine and glutamine NH2 moieties. Such data have been used to aid structural characterization of these groups. The exploitation of auto orientation of magnetic anisotropic metalloproteins represents a step ahead in the investigation of the conformational space of peripheral residues that are not fixed by the protein folding. PMID- 11200531 TI - Assignment of 1H and 15N resonances of mouse lysozyme M. PMID- 11200530 TI - 1H and 13C NMR assignments for the glycans in glycoproteins by using 2H/13C labeled glucose as a metabolic precursor. AB - In order to understand the role of the glycans in glycoproteins in solution, structural information obtained by NMR spectroscopy is obviously required. However, the assignment of the NMR signals from the glycans in larger glycoproteins is still difficult, mainly due to the lack of appropriate methods for the assignment of the resonances originating from the glycans. By using [U 13C6, 2H7]glucose as a metabolic precursor, we have successfully prepared a glycoprotein whose glycan is uniformly labeled with 13C and partially with D at the sugar residues. The D to H exchange ratios at the C1-C6 positions of the sugar residues have been proven to provide useful information for the spectral assignments of the glycan in the glycoprotein. This is the first report on the residue-specific assignment of the anomeric resonances originating from a glycan attached to a glycoprotein by using the metabolic incorporation of hydrogen from the medium into a glycan labeled with [U-13C6, 2H7]glucose. PMID- 11200532 TI - Backbone resonance assignment of human UBC4. PMID- 11200533 TI - Complete 1H, 15N and 13C assignment of the functional domain of Paracoccus denitrificans cytochrome c552 in the oxidized state. PMID- 11200534 TI - 1H, 15N, and 13C NMR resonance assignments for the Eps15 homology domain of Reps1. PMID- 11200535 TI - Sequential resonance assignments of the extracellular ligand binding domain of the human TGF-beta type II receptor. PMID- 11200537 TI - Zentralblatt fur Bakteriologie--100 years ago: first attempts and improvements of anaerobe techniques. PMID- 11200536 TI - 1H, 13C and 15N resonance assignments of the SNT PTB domain in complex with FGFR1 peptide. PMID- 11200538 TI - Staphylococcal surface display and its applications. AB - Novel surface proteins can be introduced onto the bacterial cell surface by recombinant means. Here, we describe the development of such display systems for two food-grade bacteria, Staphylococcus carnosus and Staphylococcus xylosus, and present how such engineered bacteria can be used in different applications. A study will be described in which such staphylococci were employed as vaccine delivery vehicles to elicit protective antibody responses to respiratory syncytial virus (RSV). The use of surface-engineered staphylococci as novel microbial biocatalysts, as a new type of whole-cell diagnostic devices or for adsorption of metal ions with potential environmental or biosensor applications, will also be discussed. PMID- 11200539 TI - Outer membrane proteins as surface display systems. AB - Outer membrane proteins (OMPs) of gram-negative bacteria can be used as carrier proteins to present foreign peptide epitopes on the bacterial cell surface. They all have a common structural motif of a beta-barrel that is composed of a variable number of transmembrane beta-strands connected at the periplasmic side with short turns and at the outside with long surface-accessible loops. Outer membrane proteins occur as monomers like OmpA, or assemble into trimers like the porins. Foreign gene products have been fused to surface-accessible regions of several outer membrane proteins including the porins OmpC, PhoE and LamB, lipoproteins as well as the OmpA protein. Short epitopes that are inserted into outer membrane proteins induce epitope-specific antibody responses, and are thus appealing candidates for live recombinant vaccines. Also large insertions, of more than 100 amino acids, are in some cases tolerated and do not affect the overall conformation of the carrier protein. The possible applications for outer membrane display include recombinant vaccines, peptide library screening, development of biocatalysts or whole-cell adsorbents, and adhesin-receptor interaction studies. It is expected that in the near future, development of new display systems will still increase the utilization of this emerging exciting technology. PMID- 11200540 TI - Expression of type 1 and P fimbriae in situ and localisation of a uropathogenic Escherichia coli strain in the murine bladder and kidney. AB - Adhesion is an important aspect of bacterial colonisation and induction of human disease. Escherichia coli which infects and causes disease of the urinary tract expresses several adherence factors including type 1 and P fimbriae. Their expression has been implicated in the virulence of E. coli strains infecting the urinary tract, however, the evidence for the expression of these fimbriae in situ has been implied rather than proven. Here we describe in situ detection of E. coli and of fimbrial expression in urinary tract tissue. Kidneys and bladders were isolated from mice infected with the uropathogenic isolate E. coli AD110. The tissue was sectioned and subjected to DNA-rRNA hybridization and indirect immunofluorescent staining with antibodies against type 1 and P fimbriae. Sections of both kidney and bladder stained positive for bacterial cells using a Cy3-labelled E. coli-specific rRNA probe. The same cells in these sections also stained positive for type 1 or P fimbriae using fluorescein-labelled antibodies. Tissue taken from several different time points (2, 6, and 24 hours post infection) showed the presence of bacterial cells which stained positive for fimbrial expression. Bacteria in kidney and bladder sections were observed either as individual cells associated with the mucosa or as members of microcolonies. PMID- 11200541 TI - Phylogenetic analysis of Pasteurella multocida subspecies and molecular identification of feline P. multocida subsp. septica by 16S rRNA gene sequencing. AB - Pasteurella multocida is commonly found in the oral cavity of cats and dogs. In humans it is known as an opportunistic pathogen after bites from these animals. Phenotypic identification of P. multocida based on biochemical reactions is often limited and usually only done on a species level, even though 3 subspecies are described. For molecular taxonomy and diagnostic purposes a phylogenetic analysis of the three subspecies of P. multocida based on their 16S rRNA (rrs) gene sequence was therefore carried out. We found P. multocida subsp. septica on a distinguished branch on the phylogenetic tree of Pasteurellaceae, due to a 1.5% divergence of its rrs gene compared to the two other, more closely related subspecies multocida and gallicida. This phylogenetic divergence can be used for the identification of P. multocida subsp. septica by rrs gene determination since they form a phylogenetically well isolated and defined group as shown with a set of feline isolates. Comparison to routine phenotypic identification shows the advantage of the sequence-based identification over conventional methods. It is therefore helpful for future unambiguous identification and molecular taxonomy of P. multocida as well as for epidemiological investigations. PMID- 11200542 TI - Prevalence and polymorphism of genes encoding translocated effector proteins among clinical isolates of Salmonella enterica. AB - Pathogenic Salmonella enterica strains are capable of causing local and/or systemic infections. They employ two type III secretion systems to translocate an array of virulence-associated proteins (effector proteins) directly into the cytosol of target cells of the host. Earlier data had shown that changes in the repertoire of translocated effector proteins may contribute to the adaptation of Salmonella strains to new hosts and to the emergence of epidemic strains. Using PCR and Southern blot techniques the presence of and the polymorphism among the genes encoding the translocated effector proteins SopB, SopD, SopE, SopE2, SipA, SipB, SipC, AvrA, and SptP was studied in 71 phylogenetically well characterised S. enterica subspecies I (subspecies enterica) strains of the SARB collection and in 209 clinical and epidemic isolates of S. enterica subspecies I belonging to various serovars, phage types, and genotypes. All these Salmonella strains harbour all these respective genes with the exception of sopE and avrA which have been identified in only some of them. Several of the studied genes display genetic polymorphisms (RFLP). These RFLP patterns did not show a strict correlation with the genetic distance, the grouping genes in order to understand their role in the evolution of Salmonella as a pathogen. PMID- 11200543 TI - Sequence analysis and distribution in Salmonella enterica serovars of IS3-like elements. AB - The genome of Salmonella enterica serovar Enteritidis was shown to possess three IS3-like insertion elements, designated IS1230A, B and C, and each was cloned and their respective deoxynucleotide sequences determined. Mutations in elements IS1230A and B resulted in frameshifts in the open reading frames that encoded a putative transposase to be inactive. IS1230C was truncated at nucleotide 774 relative to IS1230B and therefore did not possess the 3' terminal inverted repeat. The three IS1230 derivatives were closely related to each other based on nucleotide sequence similarity. IS1230A was located adjacent to the sef operon encoding SEF14 fimbriae located at minute 97 of the genome of S. Enteritidis. IS1230B was located adjacent to the umuDC operon at minute 42.5 on the genome, itself located near to one terminus of an 815-kb genome inversion of S. Enteritidis relative to S. Typhimurium. IS1230C was located next to attB, the bacteriophage P22 attachment site, and proB, encoding gamma-glutamyl phosphate reductase. A truncated 3' remnant of IS1230, designated IS1230T, was identified in a clinical isolate of S. Typhimurium DT193 strain 2391. This element was located next to attB adjacent to which were bacteriophage P22-like sequences. Southern hybridisation of total genomic DNA from eighteen phage types of S. Enteritidis and eighteen definitive types of S. Typhimurium showed similar, if not identical, restriction fragment profiles in the respective serovars when probed with IS1230A. PMID- 11200544 TI - In a medium containing glucose, lactate carbon is incorporated by gonococci predominantly into fatty acids and glucose carbon incorporation is increased: implications regarding lactate stimulation of metabolism. AB - The reason for stimulation by lactate of metabolism of gonococci growing in a medium containing glucose, which enhances pathogenicity by increasing growth rate, lipopolysaccharide (LPS) synthesis and protein formation, has been investigated. Tricine dodecylpolyacrylamide gel electrophoresis (SDS-PAGE) and thin layer chromatography (TLC) on homogenates of gonococci grown in this medium with [14C]lactate showed that lactate carbon was preferentially incorporated into lipid and LPS. Nuclear magnetic resonance (NMR) spectroscopy on lipid extracted from gonococci grown in the glucose containing medium with [13C]lactate showed that lactate carbon was incorporated into fatty acid moieties and not into ethanolamine or glycerol moieties. In contrast, NMR on lipid from gonococci grown with [13C]glucose indicated glucose carbon in both moieties. When unlabelled lactate was added, lipid synthesis from [l3C]glucose was stimulated and small amounts of different fatty acids were formed. The NMR data shows that gluconeogenesis from lactate carbon does not occur in the presence of glucose, suggesting that lactate is used solely for rapid production, via pyruvate, of acetyl CoA, the precursor not only for fatty acid synthesis but also for the constituents and products of the citric acid cycle, including ATP. The rapid formation of a high level of acetyl CoA is the probable reason for the stimulation of metabolism and oxygen uptake by lactate. 14C label on LPS was detected in its fatty acids. Most proteins that stained with silver in tricine SDS-PAGE were not significantly labelled by [14C]lactate in the glucose containing medium. Two of three appreciably labelled proteins were identified by N-terminal sequencing as GroEL and porin 1B, and one of the two less labelled proteins was similar to peroxiredoxin type proteins. There were no signs of specific induction of these proteins by lactate and their labelling was consistent with fatty acids in attached lipid. PMID- 11200545 TI - The multifocal electroretinogram in age-related maculopathies. AB - To measure and compare the multifocal electroretinogram in control group and patients with age-related maculopathies, 17 eyes of control subjects, 9 eyes of wet-form ARMD, 8 eyes of dry-form ARMD and 14 eyes of idiopathic macular hole were tested with VERIS Sciences 4.0. The latencies and average response densities of 6 ring retinal regions in control eyes were compared with those in ARMD and macular hole. The amplitude depression and latency prolongation were found in age related maculopathies. The changes of multifocal ERG were dramatic in wet-form ARMD and moderate in dry-form ARMD and IMH, which were correspondent with the pathological changes of the diseases. Our results suggest that the multifocal electroretinogram can be used to quantity the visual function in age-related maculopathies. PMID- 11200546 TI - Visual electrophysiology in children with tumours affecting the visual pathway. Case reports. AB - In 9 children (8-14 years of age) with orbital, suprasellar or postchiasmal tumours, visual loss was studied by visual electrophysiology in relation to ophthalmologic and neuroimaging findings. Pattern electroretinography (PERG) and pattern visual evoked potentials (PVEP) to full and half-field pattern-reversal stimulation were recorded and PERG and PVEP changes were related to the tumour location. PERG wave P50 attenuation was found associated with the central retinal dysfunction in the child with orbital rhabdomyosarcoma; PVEP wave P100 delay was associated with the optic nerve dysfunction in a child with retrobulbar chondrosarcoma and in a child with optic nerve glioma; PVEP wave P100 asymmetry was associated with the crossed fibers dysfunction in a child with hypothalamic germinoma, and PVEP wave P100 uncrossed asymmetry was associated with postchiasmal dysfunction in children with postchiasmal tumours (one with pilocytic astrocytoma and two with angioma). On the other hand, normal PERG suggested that there was no central retinal dysfunction in a child with pleomorphic adenoma of the lacrimal gland, and normal PVEP to full and half-field stimulation excluded visual pathway dysfunction at the chiasm in a child with suprasellar arachnoidal cyst. Follow-up was useful in indicating whether visual dysfunction was progressive or not. We conclude that PERG and PVEP findings contributed to understanding whether the dysfunction originated was at the retina, in the optic nerve, chiasm or postchiasmal pathway. PMID- 11200547 TI - Human photopic response to circulating glucose. AB - Circulating glucose was manipulated in young human volunteers with clinically normal vision. Fasting achieved a concentration range of 45-91 mg/dl. And sugar loading produced a range of 79-108 mg/dl. Glucose increased in all subjects. A nonparametric ANOVA provided a p=0.0005 for the significance of the concentration differences between group glucose concentrations under the two conditions in the sample. Each volunteer participated in each condition of the repeated-measures design. Clinical tests were completed before electroretinograms were recorded under photopic and scotopic adaptation conditions. Measures were made from 12 eyes. Only photopic adaptation conditions with maximal stimuli produced significant results. Inter-individual differences were robust and constrained to reduced implicit times for b-wave peaks and 30 Hz flicker implicit times. Under the elevated glucose conditions. Other variables showed very strong trends. These results confirm and extend other human indications of photopic retinal sensitivity to variations within the normal range of circulating glucose concentrations. PMID- 11200548 TI - Measuring contrast sensitivity in patients with Graves' ophthalmopathy complicated by ocular hypertension and suspect glaucoma or dysthyroid optic neuropathy. AB - The present study compares contrast sensitivity functions of patients with uncomplicated Graves' ophthalmopathy, patients with ophthalmopathy and elevated intraocular pressure or suspect glaucoma, and patients with dysthyroid optic neuropathy (DON). Aim of the study was to investigate the clinical potential for the contrast sensitivity functions (CSF) in distinguish between the groups. Contrast sensitivity measurements were obtained from twenty-seven subjects with endocrine ophthalmopathy. Group I included patients with uncomplicated ophthalmopathy (n=20 eyes); group II included patients with ophthalmopathy, intraocular pressure > or = 24 mmHg with and without early visual field defects, and no evidence of apical crowding on coronal computed tomography scan (n=14 eyes); group III included patients with DON (n=12 eyes). Contrast thresholds were determined for stationary and 6.87 Hz phase-alternating gratings at eight spatial frequencies from 0.18 to 15.7 c/deg. Data from each group was compared with data from age-matched normal subjects. Observers with uncomplicated ophthalmopathy had normal CSFs. Eyes affected with DON showed contrast sensitivity disruption at overall intermediate-high spatial frequencies. Eyes with elevated intraocular pressure or suspect glaucoma had pronounced sensitivity loss in the low frequency range (0.18-0.70 c/deg) as compared to eyes with DON. This study shows that CSF detects visual function abnormalities noninvasively in patients with complicated Graves' ophthalmopathy. Results also indicate that the clinical potential for CSF in distinguish between patients suffering from ophthalmopathy complicated by ocular hypertension or suspect glaucoma and patients with DON improves when a temporal modulation of 6.87 Hz and gratings of low spatial frequency (< 1 c/deg) are used. PMID- 11200549 TI - Dynamic topography of pattern visual evoked potentials (PVEP) in psychogenic visual loss patients. AB - We investigated to measure the objective visual acuity using pattern visual evoked potentials (PVEP) to help the diagnosis with psychogenic visual loss (PVL) who ranged in age from 7 to 14 years old. Pattern stimuli consisted of black and white checkerboard patterns (39, 26, 15 and 9') with a visual angle of 8 degrees and a contrast level of 15%. The pattern reversal frequency was 0.7 Hz. This resulted in an average of 100 PVEP per session. Visual acuity of 0.1 was consistent with the 39' pattern, 0.2 with the 26' pattern, 0.5 with the 15' pattern, and 1.0 with the 9' pattern. As the results, five PVL patients could measure visual acuity with this method in the present study. The PVEP is useful in evaluating the visual acuity and helped to diagnose the PVL patients. In addition we used the dynamic topography to study the difference in the results of the PVEP. The dynamic topography obtained from the results of the PVEP was analyzed. The flow type of the P100 component diverged into three types (separated type, hollow type and localized type) in the PVL patients and the normal children. The localized type was observed in 59.1% of normal children and in 56.3% of PVL patients. While the separated type was shown in 6.8% of normal children and in 8.3% of PVL patients. There were not significant differences between the PVL patients and the normal children in each type. PMID- 11200550 TI - [Epidermoid cyst of the cerebellopontine angle. Report of a case]. AB - Epidermal cysts of the cerebello-pontine angle (CPA) are lesions arising from epidermal remainders having an expansive and slow growth sitting on the PCA space or on the temporal bone. Are diagnosed approximately in the fourth life's decade by its deficient or irritant symptoms related to VIIth and VIIIth cranial nerves. It is important the nuclear magnetic resonance exam because the specific radiologic characteristics that distinguish these cysts from other conditions of CPA as neuromata or meningiomata. PMID- 11200551 TI - [Vertigo in the elderly: otorhinolaryngologic approach]. AB - Dizziness is a common but little understood ailment of old people. Its presence is the origin of an important incapacity associated with lack of personal autonomy. Clinical and electronystagmographic findings of aging individuals enduring imbalance and coming to our Department allowed us to accept that those cases in which the cause could be identified it was on clinic data, being of scarce utility the other exams done. PMID- 11200552 TI - [Nasopharyngeal bacterial flora and secretory otitis in adults]. AB - The AA. have realized a prospective study of the links between the bacterial flora of the nasopharynx and the secretory otitis media in grown-up people. For achieving this purpose nasopharyngeal smears of rhinopharyngeal samples belonging to 85 otitic patients and other 85 healthy adults were cultivated. Statistical analysis showed that the otitis cases presented with 63.6% of microorganisms potentially pathogenic, being the 17.6% the percentage among healthy individuals (p < 0.001). Microorganisms more frequently encountered were: Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis and Staphylococcus aureus. After the medical treatment those patients recovered showed an increase of saprophyte flora from early 36.4% till 86% (p < 0.001). It could be appreciate a seasonal influence in the debut of this malady specially in winter. PMID- 11200553 TI - [Complications of thyroid surgery. Report of 683 thyroidectomies]. AB - Most important complications of thyroid gland surgery are recurrent paralysis (which usually results from section, stretching or devascularization of this neural branch) and parathyroid lesions resulting from unnoticed removal of more than two of these glands or through necrosis because deficient blood supply. We present a study about the complications of thyroid surgery based on the thyroid surgery done in our ENT Service during 1979-1998 term. An amount of 683 cases make the series. The 86% were female and 14% male, with a mean age of 40-50. Surgical techniques realized were: hemithyroidectomy (15.3%) and isthmectomy (2.9%). About 7.4% of patients were reoperated. Stated complications were: local (serohematoma 4.1%, infection 1.2%, postoperative hemorrhage 1.2%) and recurrent paralysis (unilateral transitory 2.6% and unilateral definitive 1.6%; there wasn't any case of bilateral palsy) and superior laryngeal nerve paralysis (1.4% as well as hypoparathyroidism (transitory 22.7% and definitive 5.3%). These complications were most frequent in reoperated cases and in total and subtotal thyroidectomies. In most of these series the incidence of recurrent palsy range between 1.5% and increases more than 9.5% in surgical check and the hypoparathyroidism incidence ranges over 25%. PMID- 11200554 TI - [Laryngeal cancer at the Provincial Hospital of Rosario]. AB - The paper is an abridgement about the task and activities done by the resident's teamwork, under the guidelines of the chief of the Head and Neck Surgery Department, at Provincial Hospital of Rosario de Santa Fe (Argentina), with regard to epidemiology, clinical, anatomopathological and therapeutics features and follow-up care of laryngeal cancerous patients they treated in the Hospital. PMID- 11200555 TI - [Otolaryngologic disorders caused by esophageal reflux]. AB - The authors through an accurate analysis of the literature make a synthesis of the most recent knowledge about the correlation existing between the distal and proximal gastroesophageal reflux (GER) and a series of common otolaryngologic symptoms whose aetiology is doubtful, in order to explain its most significative physiopathological and clinic aspects. The diagnostic modalities able to reveal the presence of the correlation and the adequacy therapy to cure the disease are also discussed. PMID- 11200556 TI - [Primary carcinoma of the trachea. Report of 2 cases]. AB - Tumours of the trachea remain relatively rare, the incidence of tracheal carcinomata is less than 0.1 per cent. Tumours of the larynx and lungs are, respectively, 75 and 180 times more frequent than malignant lesions of windpipe. Two patients with primary tracheal tumours were evaluated. The present study was undertaken in order to describe and analyse the most pertinent clinical and pathologic features of tracheal carcinomas as they relate to treatment and prognosis. PMID- 11200557 TI - [Tonsillar angiofibroma]. AB - We report in this paper a case of a tonsillar angiofibroma, whose histopathological features did not differ from its nasopharyngeal counterpart. In an exhaustive review done we have only found another one reference, in the german literature of such location. PMID- 11200558 TI - [Results of multinodular goiter surgery]. AB - In order to assess the main complications following surgical treatment of multinodular goiter (total thyroidectomy) a prospective historical study was made in 179 patients operated between 1985 and 1997 in our Department. Permanent hypocalcemia was encountered in 2.2 percent of our cases and permanent recurrent paralyses in 0.5 percent, being null and void the mortality rate. Other complications evaluated include: serohematoma, postoperative bleeding, wound infection and pulmonary embolism. To sum up, total thyroidectomy is a relative safe procedure in experienced hands for both patient and surgeon. PMID- 11200559 TI - [Infantile facial paralysis: diagnostic and therapeutic features]. AB - This paper deals with a series of 11 cases of peripheral unilateral facial paralyses affecting children under 15 years. Following parameters are reviewed: age, sex, side immobilized, origin, morbid antecedents, clinical and neurophysiological explorations (electroneurography through magnetic stimulation) and the evolutive course of the cases. These items are assembled in 3 sketches in the article. Clinical assessment of face movility is more difficult as the patient is younger, nevertheless electroneurography was possible in the whole group. Clinical restoration was complete, excepting one complicated cholesteatomatous patient. Some aspects concerning the etiology, diagnostic explorations and management of each pediatric case are discussed. PMID- 11200560 TI - The academic cup: part II. PMID- 11200561 TI - Containment of Helicobacter hepaticus by use of husbandry practices. PMID- 11200562 TI - Age differences in thickness of the epidermis of miniature and domestic swine. PMID- 11200563 TI - Helicobacter hepaticus infection triggers inflammatory bowel disease in T cell receptor alphabeta mutant mice. AB - The T cell receptor alpha chain-deficient (TCR alpha-/-) and TCR beta chain deficient (TCR beta-/-) mice develop chronic intestinal inflammation that resembles inflammatory bowel disease by 3 to 4 months of age. The objective of the study reported here was to determine the role of infection with the bacterial pathogen Helicobacter hepaticus in the pathogenesis of disease in TCR alphabeta mutant mice. The H. hepaticus-infected TCR alphabeta mutant mice were rederived by use of embryo transfer to produce Helicobacter-free animals. Helicobacter-free TCR alpha-/-, TCR beta-/-, and TCR alpha-/- beta-/- mice were inoculated with H. hepaticus. Experimentally infected mice and uninfected control mice were examined for intestinal lesions at 3, 6, and 9 months after inoculation. The TCR alphabeta mutant mice inoculated with H. hepaticus developed intestinal epithelial cell hyperplasia and mucosal inflammation. By 6 months after inoculation, infected animals had moderate cecal and colonic lesions. Helicobacter-free TCR alpha-/- mice, but not TCR beta-/- or TCR alpha-/- x beta-/- mice, also developed H. hepaticus-independent colitis by 9 months after inoculation. Infection with H. hepaticus is sufficient to cause chronic proliferative intestinal inflammation in TCR alphabeta mutant mice. However, H. hepaticus infection is not necessary for intestinal disease in TCR alpha-/- mice. PMID- 11200565 TI - Anti-Thy-1 monoclonal antibody-induced glomerulonephritis in Mongolian gerbils. AB - Two novel murine monoclonal antibodies (mAbs) were produced to the Thy-1 molecule of Mongolian gerbils (Meriones unguiculatus). These mAbs, HUSM-M.g.27 of IgG1 isotype and HUSM-M.g.40 of IgG2a isotype, immunohistochemically reacted with the thymus, nervous system, and glomerular mesangium in partially different manners, suggesting that they recognize distinct epitopes, although they reacted with Thy 1 antigen, with apparent molecular weight of about 25 kDa, on gerbil thymocytes. Mild and severe forms of mesangioproliferative nephritis after glomerular deposition of the antibody was observed in gerbils administered mAbs HUSM-M.g.27 and HUSM-M.g.40, respectively, intraperitoneally, with or without guinea-pig serum as supplementary complement. Distinct pathogenicity and requirement of guinea pig serum for pathologic sequels are discussed as they relate to the rat model of anti-Thy-1-induced glomerulonephritis. PMID- 11200564 TI - Modification of immunologic and hematologic variables by method of CO2 euthanasia. AB - BACKGROUND AND PURPOSE: The major goal was to determine whether variations in the method of CO2 euthanasia would induce significant immunologic differences. METHODS: Young adult C57BL/6 mice (n = 40) were euthanized, using four regimens: 70% CO2/30% O2; 70% CO2/30% O2-->100% CO2; 100% CO2-naive chamber; and 100% CO2 pre-charged chamber. Time to recumbency and euthanasia and body, liver, lung, spleen, and thymus masses were determined. Blood and spleen were further evaluated for leukocyte, lymphocyte, and thrombocyte counts, erythrocyte characteristics, distribution of lymphocyte subpopulations, spontaneous and mitogen-induced blastogenesis, complement activity, and cytokine production. RESULTS: Time to euthanasia was five- to eightfold longer in mice exposed to 70% CO2/30% O2 than that for any other group. There were slight increases in mean erythrocyte volume (MCV) and mean erythrocyte hemoglobin (MCH) for all groups, compared with those for the 100% CO2 pre-charged group. Circulating cytotoxic T (CD8+) lymphocyte percentages and numbers, and spontaneous blastogenesis of leukocytes in blood and spleen, also were affected by euthanasia method. CONCLUSIONS: The method of CO2 euthanasia can result in significant differences in immunologic/hematologic variables. Thus, consistency in euthanasia procedures may be important in accurate interpretation of research data. PMID- 11200566 TI - Gross and microscopic anatomy of the extraorbital lacrimal gland of the common marmoset (Callithrix jacchus). AB - PURPOSE: The lacrimal gland is often selected for microscopic examination in toxicologic studies. However, this gland is difficult to find within the orbit in marmosets at necropsy. Therefore, we examined the extraorbital lacrimal glands in marmosets. METHODS: The formalin-fixed craniums of four marmosets were used in a topographic study to confirm location of the lacrimal gland, and the results were applied to a routine toxicologic study in marmosets. RESULTS: The extraorbital lacrimal gland was located on the temporal surface of the zygomaticofrontal process and was covered with the temporalis muscle. The gland was easily detached from the surrounding tissue, and its histologic features were the same as those of the intraorbital lacrimal gland. CONCLUSIONS: The extraorbital lacrimal glands have been reported in some New World monkeys, but to the authors' knowledge, this is the first report in marmosets. Identification and characterization of this gland will be useful for toxicologic studies in marmosets. PMID- 11200567 TI - Experimentally induced infection with autonomous parvoviruses, minute virus of mice and H-1, in the African multimammate mouse (Mastomys coucha). AB - To determine whether the multimammate mouse (Mastomys coucha) could be used to evaluate rodent parvovirus-based vectors, neonates were subcutaneously inoculated with minute virus of mice (prototype strain, MVMp) or rat parvovirus H-1. The course of infection with both viruses was similar. Seroconversion occurred within two weeks after virus inoculation, as detected by use of hemagglutination inhibition assays, and antibody titers remained high for the entire observation period of 12 months. Viral DNA and infective virions were detected in several organs of inoculated animals prior to seroconversion, as measured by use of Southern blotting and plaque assays, respectively. Infective particles subsequently became undetectable, whereas viral DNA imprints persisted in distinct organs for at least nine months. Clinical signs of parvovirus infection appeared around six weeks after virus inoculation, and consisted of hemorrhages, stunted growth, and transient hair color changes. Sudden death occurred in a significant fraction of animals infected with MVMp, but not H-1 virus, at the time of weaning. Altogether, MVMp, which is innocuous to its natural host, the mouse, and H-1 virus, which is poorly pathogenic to the rat, appear to be pathogenic for Mastomys coucha. PMID- 11200568 TI - Mycoplasma pulmonis genital disease: effect of rat strain on pregnancy outcome. AB - BACKGROUND AND PURPOSE: Mycoplasma pulmonis is a natural pathogen of the respiratory and genital tracts of rats. Differential susceptibility and severity of the respiratory form of the disease, known as murine respiratory mycoplasmosis (MRM), exist between rat strains. We now report that specific rat strains vary in susceptibility to genital tract infection and pregnancy outcome. METHODS: Specific-pathogen-free (SPF) female F344, LEW, Wistar (WIS) and Sprague Dawley (SD) rats were intravaginally inoculated with 3 x 10(7) colony-forming units (CFU) of M. pulmonis strain X1048 or sterile diluent, and allowed to breed at 10 days after inoculation. Pregnant dams and pups were necropsied within 24 hours of parturition. At necropsy, culture for M. pulmonis was performed on dam and pups, and adverse effects on pregnancy outcome were assessed by determination of the incidence of infertility, fetal resorption, stillbirths, changes in litter size, and pup birth weight. Blood from dams was collected prior to inoculation and at time of necropsy for measurement of IgM and IgG antibodies to M. pulmonis. RESULTS: At time of necropsy, WIS (50%) and SD (60%) dams had a higher frequency of M. pulmonis culture positivity in the genital tract than did LEW (22.2%) and F344 (17.6%) dams. Dams that were still infected with M. pulmonis at time of necropsy had various complications. The SD rats had the greatest degree of adverse effects on pregnancy outcome, which were: infertility, decreased litter size (P < or = 0.01), decreased pup birth weight (P < or = 0.01), increased frequency of resorptions, stillbirths (P < or = 0.05), and the highest rate of pup pulmonary infection (23.1%) (P < or = 0.001). Despite a 50% colonization rate, WIS dams were the least adversely affected. The WIS pups born from M. pulmonis. infected dams had slight decrease in birth weight, and only 6% had pulmonary infections. The LEW infected dams developed infertility and lower numbers of liveborn pups without evidence of vertical transmission. The F344 infected dams had lower numbers of liveborn pups that were smaller than their control counterparts, and none had pulmonary infections. None of the animals had detectable IgM and IgG antibodies to M. pulmonis before inoculation. At time of necropsy, all animals inoculated with M. pulmonis developed significantly (P < or = 0.001) higher amounts of M. pulmonis IgG and IgM antibodies, with SD rats developing the highest amounts (P < or = 0.005). CONCLUSIONS: Both F344 and LEW rats are more resistant to vaginal inoculation with M. pulmonis than are WIS and SD rats. However, only SD dams suffered severe adverse effects on pregnancy outcome. The SD dams also had the greatest IgM and IgG antibody response to M. pulmonis. Our studies clearly indicate differences among rat strains in their susceptibility to vaginal inoculation with M. pulmonis and in secondary complications associated with infection. This system may be a useful model for determining host-specific factors that influence the outcome of natural mycoplasmal infections of the genital tract. PMID- 11200569 TI - Buprenorphine given after surgery does not alter renal ischemia/reperfusion injury. AB - BACKGROUND AND PURPOSE: Potential drugs for human acute renal failure are often tested in an animal model of renal ischemia/reperfusion injury. Analgesics are often not given after surgery because of concerns that they would alter renal function. Therefore, we tested whether postoperative analgesia would alter animal health or affect the degree of renal injury. METHODS: Mice were subjected to either 32 or 37 minutes of renal ischemia, given two or six doses of buprenorphine or vehicle at 12-hour intervals, and followed for 72 hours. In some animals, we measured body temperature and physical activity by use of telemetry. RESULTS: Animals treated with buprenorphine recovered more rapidly from surgery based on postoperative activity, and had a small but not significant tendency for faster restoration of normal body temperature. Animals treated with buprenorphine had less weight loss after 37 minutes of ischemia. Buprenorphine given after surgery did not influence the degree of renal injury after ischemia/reperfusion. CONCLUSIONS: Buprenorphine should be given after renal ischemia-reperfusion surgery because administration of the proper analgesic improved animal health without interfering with the renal ischemia/reperfusion model. Analgesic treatment at the time of the operation and 12 hours after was sufficient. Buprenorphine may reduce the post-surgical stress response, and thus potentially improve the specificity of testing for drugs that reduce or treat renal injury. PMID- 11200570 TI - Median effective dose determination and histologic characterization of porcine (Sus scrofa domestica) dermal lesions induced by 1540-nm laser radiation pulses. AB - BACKGROUND AND PURPOSE: Light amplification by stimulated emission of radiation (laser) systems operating in the so-called "eye safe" region are gaining widespread use in industry, medicine, and military applications. This research effort was geared to study the effects of laser tissue interaction on human skin by using in vivo porcine skin as an animal model. The goals of the study were to determine the median effective dose (ED50) for 1540-nm laser exposures, to evaluate the Yorkshire pig and the Yucatan mini-pig as animal models for laser exposure, and to characterize laser-induced skin lesions histologically. METHODS: A 1540-nm wavelength laser was used to expose multiple sites on the flanks of 10 pigs, using 0.8-ms pulses, ranging from 7 to 96 joules (J)/cm2. Single pulses were delivered to the flank of Yorkshire and Yucatan pigs in a grid pattern. Exposure sites were evaluated immediately after exposure and at 1 hour and 24 hours for presence of gross lesions. Representative biopsy specimens were collected from lesion sites for histologic evaluation at the 24-hour endpoint. RESULTS: The ED50 for the two breeds differed in the amount of energy required to induce dermal lesions. Grossly, lesions in each breed were well demarcated and pale gray to brightly erythematous. Microscopically, lesions had epidermal layer damage as cellular swelling and nuclear pyknosis, loss of cellular detail, and coagulation necrosis at the dermal layer. CONCLUSIONS: Findings suggest the presence of a different mechanism of laser-tissue damage in these two breeds. Photo-thermal mechanism appears to induce the skin lesions in the Yorkshire pig, whereas photo-thermal and photochemical mechanisms appear to be involved in lesion formation in the Yucatan mini-pig. All data obtained in this study will become part of database used by the American National Standards Institute (ANSI) to recommend laser safety standards for the occupational health and safety programs (OHSP), which will be used by industry and the military to base and update their current OHSP. PMID- 11200571 TI - Cardiopulmonary effects of sevoflurane in Garnett's greater bush baby (Otolemur garnettii). AB - PURPOSE: A study was conducted to assess the cardiopulmonary and anesthetic effects of sevoflurane anesthesia on Garnett's Greater Bush Baby (Otolemur garnettii). METHODS: Anesthesia was induced in ten animals with 8% sevoflurane and was maintained by use of 2.5% sevoflurane for 30 minutes. Induction and recovery times were recorded. Heart and respiratory rates (RR), end-tidal carbon dioxide concentration (ET CO2), arterial blood pressures, relative arterial blood oxygen saturation (SpO2), arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), and pH were monitored. Pre- and poststudy CBC and serum biochemical values were compared. RESULTS: Anesthesia induction was rapid (75+/-8.7 seconds [mean +/- SEM]) and smooth. Heart rate significantly increased initially, then decreased significantly over the remaining 30 minutes. There were no significant changes in RR, SpO2, ETCO2, or arterial blood pressure. The PaO2 values significantly increased in the 10- to 30 minute samples. The PaCO2 values remained steady in the 10- to 30-minute samples. A significant decrease was seen in white blood count, calcium, and total protein (TP) values, compared with values in pre-anesthesia samples. Recovery from anesthesia was smooth and rapid, with extubation at 24+/-5.8 seconds. CONCLUSIONS: At the concentrations used in this study, sevoflurane appears to be a safe and effective agent for induction and maintenance of anesthesia in O. garnettii. PMID- 11200572 TI - Survey of effects of anesthesia protocols on hemodynamic variables in porcine cardiopulmonary resuscitation laboratory models before induction of cardiac arrest. AB - OBJECTIVE: An advantage of animal models in cardiopulmonary resuscitation (CPR) research is the possibility to control confounding variables that may be impossible to standardize in clinical trials. A neglected effect of the anesthesia protocol in porcine CPR studies may be its impact on hemodynamic variables before induction of cardiac arrest. Accordingly, the purpose of the study reported here was to evaluate published CPR reports with regard to their anesthesia protocol. METHODS: Of 100 articles that reported on laboratory models simulating cardiac arrest between 1987 and 1997 in peer-reviewed journals, 25 met inclusion criteria and were analyzed for values of coronary perfusion pressure, mean arterial pressure, heart rate, temperature, and cardiac index before induction of cardiac arrest. Subsequently, mean values for all animals in a given report were calculated and corrected for group size; statistical analysis was not performed since this was a survey only. RESULTS: Different anesthesia protocols resulted in a widely distributed pattern of hemodynamic variables prior to induction of cardiac arrest. Ranges compared with reference values were: heart rate, 100 to 122 beats/min versus 105+/-11 beats/min; mean arterial pressure, 68 to 130 mm Hg versus 102+/-9 mm Hg; coronary perfusion pressure, 55 to 114 mm Hg (no reference value); cardiac index, 69 to 152 ml/kg/min versus 147+/-22 ml/kg/min; body temperature, 37 to 38.5 degrees C versus 38.5+/-0.7 degrees C. CONCLUSION: The anesthesia protocol may have an impact on hemodynamic variables before induction of cardiac arrest in CPR studies. PMID- 11200573 TI - Retrospective analysis of an outbreak of B virus infection in a colony of DeBrazza's monkeys (Cercopithecus neglectus). AB - In 1981, an outbreak of herpetic disease developed in a colony of DeBrazza's monkeys (Cercopithecus neglectus). In seven of eight infected animals, clinical signs of infection included vesicular and ulcerative lesions on the lips, tongue, and/or palate. Histologic examination of lesions revealed intranuclear inclusion bodies, and electron microscopy revealed nucleocapsids and virions with typical herpesvirus morphology. Although a virus was isolated that appeared similar to monkey B virus, techniques available at the time did not allow precise identification of the virus. Analysis of serum from one surviving monkey collected 12 years after the outbreak revealed a pattern of reactivity characteristic of B virus-positive serum on the basis of results of ELISA and western immunoblot analysis. Polymerase chain reaction analysis of archived paraffin-embedded tissue specimens and molecular analysis of the one viral isolate obtained from a DeBrazza's monkey indicated that the virus responsible for the outbreak was a new genotype of B virus. Testing of sera from lion-tailed macaques (Macaca silenus) housed in an adjacent cage at the same zoo indicated that these animals harbored this virus and, thus, were the likely source of the virus that infected the DeBrazza's monkeys. This study documents usefulness of archiving samples from disease outbreaks for later analysis. In addition, this incident underscores the importance of considering herpes B virus infection when outbreaks of disease having characteristics of herpetic infections develop in nonhuman primates kept at institutions that also house macaques. PMID- 11200574 TI - Trypanosoma cruzi infection of squirrel monkeys: comparison of blood smear examination, commercial enzyme-linked immunosorbent assay, and polymerase chain reaction analysis as screening tests for evaluation of monkey-related injuries. AB - BACKGROUND AND PURPOSE: Wild-caught New World monkeys (NWM) from Central or South America are often infected with Trypanosoma species, including T. cruzi. In humans, T. cruzi causes Chagas' disease. Even in closed monkey colonies, T. cruzi can be propagated by blood-to-blood exposure, sexual activity, and transplacental transmission. Animal handlers and laboratory staff who deal with blood and tissues from infected NWM are at riskfor acquiring Chagas' disease via accidental exposure. METHODS: We screened 162 blood samples from wild-caught Saimiri sp. monkeys for Trypanosoma species infections by use of blood smear examination, ELISA, and polymerase chain reaction (PCR) analysis. Blood samples from 19 employees with recent history of monkey-associated injuries also were tested. RESULTS: Six percent (10/162) of the monkey samples were T. cruzi positive on the basis of blood smear examination results, 10.4% (17/162) were positive by ELISA results, and 26.5% (43/162) were positive by PCR results. Other organisms identified by PCR analysis included T. rangeli in two animals, Plasmodium spp. in two animals (P. malariae confirmed by PCR results) and microfilariae in one animal (morphologically, Mansonella perstans). Evidence of trypanosome infection was not found in the 19 employee samples on the basis of results of any of the three aforementioned tests. CONCLUSIONS: Close attention must be paid to worker safety where wild-caught NWM are used. The PCR analysis has a clear advantage over conventional techniques (ELISA, blood smear) for screening NWM for trypanosome infections during quarantine and after employee injury. PMID- 11200575 TI - Diagnosis and management of atypical Mycobacterium spp. infections in established laboratory zebrafish (Brachydanio rerio) facilities. AB - Two established zebrafish colonies experienced increased mortality and decreased reproductive performance. Initial examination of several fish from one facility revealed hyperemic gills, petechia around the opercula, abdominal distention, and emaciation. Affected fish had congested liver with inflammation and multifocal hepatic necrosis. Large numbers of acid-fast-positive, rod-shaped bacteria were evident in multiple tissues and the blood. Mycobacterium fortuitum was subsequently isolated from several fish. Zebrafish from the second facility had skin erosions and ulceration along the flank just caudal to the pectoral fins. Large numbers of acid-fast-positive, rod-shaped bacteria were observed within the necrotic centers of well-demarcated, multifocal granulomas in gonads, liver, and peritoneum from affected fish. Mycobacterium abscessus and M. chelonae were isolated and identified biochemically. Definitive diagnosis in these outbreaks was obtained by culture on selective media. Because Mycobacterium spp. grow extremely slowly and positive confirmation may require 45 to 60 days, Mycobacterium species-specific polymerase chain reaction analysis was used to provide a rapid screening assay for Mycobacterium spp. as well as for verification of culture results. To our knowledge, this is the first documentation of mycobacterial infection in laboratory-maintained zebrafish and provides guidelines for diagnosis, management, and prevention of atypical mycobacteriosis in laboratory zebrafish colonies. PMID- 11200576 TI - Iridodialysis in a rhesus macaque: a case report. AB - During routine physical examination, a five-year-old male rhesus macaque (Macaca mulatta) was observed to have gaps in the right iris. Ophthalmic examination revealed inferior and superior iridodialysis with an anterior cortical cataract. The optic nerve head and fundus were normal. Uninvolved areas of the iris and anterior-chamber angle were normal on the basis of results of gonioscopy. Tonometry revealed normal intraocular pressure. The cause of the iridodialysis in this monkey's eye was not known. The animal had been housed individually since arrival due to requirements of the research protocol. Although the concomitant cataract supports a traumatic cause, there was no history of cranial or other ocular injuries. Trauma from fighting through the cage walls, self-trauma or falling inside the cage while under sedation cannot be ruled out. Multiple hematologic evaluations disclosed no abnormalities. This animal did not manifest behavioral abnormalities or any indication of pain. Therefore, treatment was not initiated. Intraocular pressure continues to be monitored at least semiannually. PMID- 11200577 TI - Disease attributed to Mycobacterium chelonae in South African clawed frogs (Xenopus laevis). AB - The fast-growing nontuberculous mycobacterial species Mycobacterium chelonae was isolated from six captive South African clawed frogs (Xenopus laevis) with chronic weight loss and nonhealing ulcerative skin lesions. Three of the M. chelonae isolates were evaluated to confirm the species identification using polymerase chain reaction restriction analysis. Disease associated with M. chelonae is reported mainly in people and in fish. To our knowledge, this is the first report of disease associated with M. chelonae in a colony of captive Xenopus sp. PMID- 11200581 TI - Assault and battery, or legitimate treatment? AB - In response to cases of high-handed medical interventions and treatments, a debate on the legal justification of operations and the relevance of patients' consent developed among German-speaking jurists in the 1890s. The view that surgery was objectively physical injury or battery, which went merely unpunished through the patient's consent, was highly contested among legal experts and firmly rejected by doctors. Various proposals to justify indicated medical treatment without consent were discussed. German jurisdiction, however, endorsed the battery theory of medical interventions and thus prepared the way for the concept of informed consent in medicine. PMID- 11200583 TI - [Medicines and thermal treatment in Pautalia, Thrace]. AB - The city of Pautalia (Kyustendil in Bulgaria) is located near thermal springs in the Strymon valley (Strouma), on a site occupied from the Iron Age onward by the Thracian tribe of Dentheletes. The temple of Asclepios and the walls of Pautalia, located on the hill of Hissarlaka, as well as the roman thermae in the center of modern Kyustendil are among the more important archaeological vestiges in the area. In 1990, near the village of Dragodan, district of Kyustendil, different surgical instruments in bronze were unearthed in a tumulus attributed to the roman period (IInd century A.D.). During the excavation of another tumulus in 1992, a truly exceptional discovery was made near the town of Kotcherinovo, district of Kyustendil: A variety of medicines were discovered in a small bronze case, dating from the roman period (IInd century A.D.). The complete results of the analysis of these substances and few hypotheses about their possible use are presented in this publication. PMID- 11200584 TI - Vestibular and cochlear toxicity of aminoglycosides--a review. AB - Recently, there have been many reports describing the efficacy of intratympanic aminoglycoside injection for the treatment of intractable vertigo in patients with Meniere's disease. However, the number of injections and the amount of drug injected varies, with concomitant variation in the side-effect of hearing deterioration. To identify drugs that are more selectively vestibulotoxic, we have reviewed the ototoxicity of aminoglycosides, focusing on differences between vestibulo- and cochleotoxicity. At present, the basis for the different effects of each drug is unknown. The mechanisms of vestibulo- and cochleotoxicity are deemed worthy of further study. PMID- 11200585 TI - The reinnervation of regenerated hair cells in the basilar papilla of chicks after kanamycin ototoxicity. AB - When newly hatched chicks were injected with kanamycin on 8 successive days, the hair cells were destroyed completely in the area 0.4 to 0.8 mm from the proximal end of the basilar papilla. At this time, and 1 and 7 days following the completion of 10 days of injections, the nerve fibres in the basilar papilla of chicks show no sign of injury. On the first day following 10 days kanamycin administration the regenerated hair cells obtained not only afferent innervation, but also efferent innervation. At 15 days following drug cessation, afferent innervation of the regenerated hair cells was already similar to the controls, and the thresholds measured at this time were significantly better than those at 1 and 7 days. The chalice efferent terminals did not appear until the 60th day of drug cessation. Efferent innervation of the regenerated hair cells also approached maturity at this time. Compared with the half month after the completion of drug injection, the hearing of birds had no evident increase. It was obvious that afferent innervation of the regenerated hair cells was related more to the recovery of hearing than efferent innervation. The regenerated hair cells beginning reinnervation early and maturing were important factors influencing the recovery of the birds' hearing function after kanamycin ototoxicity. PMID- 11200586 TI - Development of the middle ear in neonatal chinchillas. I. Birth to 14 days. AB - Measures of middle-ear function in humans show large differences among neonates, infants, and adults. In contrast, hearing sensitivity is essentially mature at birth. Hypotheses that have been proposed to explain the developmental changes in middle-ear function include: (i) contaminating effects of the immature neonatal ear-canal wall and (ii) persistent fetal tissue in the ear canal, tympanic membrane (TM), and middle-ear space. To better understand the relationships between middle-ear function, hearing sensitivity and the structure of the middle ear, 30 chinchillas, aged 1-14 days, were studied. Middle-ear function was assessed by multifrequency tympanometry with probe tones ranging from 226 to 2,000 Hz. Hearing sensitivity was measured by auditory brainstem response using clicks and 1, 2, 4, and 8 kHz tone bursts. Structural characteristics were analyzed from temporal bone histologic preparations. At all frequencies, the acoustic admittance of the neonatal car is very low and tympanometric patterns are complex and irregular, compared to adult animals. The admittance is essentially constant from 1 to 14 days, indicating that developmental changes occur over a much wider age span than that investigated here. Hearing sensitivity of the chinchilla appears to be mature at birth. Histologic analysis indicated that there were no age-related changes in TM thickness, TM diameter, distance from TM to promontory, and stapes footplate diameter. There were small increases in bone thickness, middle-ear area, mastoid bulla area, and in the perimeters of the middle ear and mastoid bulla. There were no significant amounts of loose mesenchyme or other fetal tissue in the middle-ear space. PMID- 11200587 TI - Mucin gene expression in cultured human middle ear epithelial cells. AB - For the advanced study of the cell and molecular biology of middle ear mucosa, an in vitro cell culture system is required. Although middle ear epithelial cells have been cultured from various species of laboratory animal, there have been no reports concerning a serial subculture system of human middle ear epithelial cells. In this paper, we describe the establishment of a primary culture system of human middle ear epithelial cells using a serum-free conditioned medium and the characterization of these cells by the expression of phenotypic characteristics of epithelial cells and mucin genes. Cultured cells were anchorage-dependent in terms of growth and showed a polygonal cobblestone-like appearance: desmosomes in the cell junction were observed by electron microscopy. In the immunocytochemical study, cytokeratin (epithelial cell marker) was expressed in all cultured cells. but von Willebrand factor (endothelial cell marker) was not. Unexpectedly, vimentin (fibroblast marker) was locally expressed, and a double stain showed the co-expression of both cytokeratin and vimentin in the same cell. The products of reverse transcriptase polymerase chain reaction from cultured cells yielded distinct bands compatible with the expected sizes of the MUC1, MUC2, MUC5AC and MUC5B genes. This culture system will allow us to prepare the cell line and to perform advanced studies of human middle ear mucosal biology. PMID- 11200588 TI - Exostoses and cavernous venous formation in the external auditory canal of the hooded seal as a functional physiological organ. AB - Exostoses of the external auditory canal (EAC) develop after protracted mechanical, chemical or thermal irritation in particular. This is a common disorder among aquatic sportsmen and has been considered unique to Man. We dissected and photodocumented the EACs of 5 newborn and 3 adult Hooded Seals (Cystophora cristata). Serial sections of the EACs were prepared for light microscopic evaluation after staining with haematoxylin-eosin or toluidine blue. All EACs exhibited a firm, broad-based. mountain peak-shaped exostosis on the floor of the meatus, lateral to the eardrum. In addition, the meatal skin of the bony EAC harboured large venous sinuses. The exostosis and venous sinuses of the seal EAC participate in the protection of the sensitive hearing apparatus, particularly the pars tensa portion of the drum, during divine. PMID- 11200589 TI - Effects of retinoic acid, triiodothyronine and hydrocortisone on mucin and lysozyme expression in cultured human middle ear epithelial cells. AB - Mucous hypersecretion is a major complication of otitis media and can prolong the disease course and increase morbidity. Mucin, a major component of mucus, is a macromolecular complex of glycoprotein and makes mucus viscous. Lysozyme is a secretory element of the middle ear mucosa. which has a non-specific and innate antibacterial function. We attempted to identify factors that regulate these secretory products and their morphological phenotype using cultured human middle ear epithelial cells. Cellular differentiation was induced by creating an air liquid interface on culture day 9 in serum-free conditioned media. Omission of retinoic acid (RA) caused decrease in the secretion of mucin and lysozyme, and in the cellular expression of MUC 2, MUC 5AC and MUC 5B mRNA. In contrast, removal of triiodothyronine (T3) caused an increase in the secretion of mucin and the level of MUC5AC mRNA. When hydrocortisone (HC) was removed from the media, the secretion of mucin was decreased with out an apparent change of message level. The expression of MUC 1 mRNA was not changed by the respective deficiency of RA. T3 or HC. The effect of T3 or HC on lysozyme was not significant. This study shows that RA, T3 and HC influence the morphological phenotype and the secretory function of mucin and lysozyme in cultured human middle ear epithelial cells. This culture system can serve as an in vitro model for study of the regulation of various cellular secretions in human middle ear epithelium. PMID- 11200590 TI - Clinicopathologic growth factors in vestibular schwannomas: a morphological and immunohistochemical study of 69 tumours. AB - Tumour growth of vestibular schwannomas is still difficult to predict. The aim of our study was to determine whether any defined histopathological feature was correlated with the clinical course. We did a retrospective study with 69 paraffin-embedded tumours to establish whether the number of vessels, blood cells extravasation or degree of inflammation, all semi-quantitatively assessed, could be indicative of potential of growth. An immunohistochemical study was also performed with an endothelial marker CD34, the leukocyte common antigen CD45 and the estrogen and progesterone hormone receptors. All these parameters were correlated with patient's age, duration of symptoms (d), with a clinical growth index (CLI = tumour size/d). No clinical parameters proved to be predictive of tumour growth. Tumour size was significantly (p = 0.01) related to the number of vessels and we found a significant relationship between the clinical growth index (CLI) and total number of vessels, especially when duration of symptoms lasted less than 1 year (p < 0.001). However, we found no relationship between duration of symptoms or CLI and CD34 index. The degree of inflammation was significantly correlated (p = 0.007) with duration of symptoms when it lasted more than 1 year. The CD45 index and the semi-quantitative evaluation of the inflammation were well correlated (p = 0.001). No estrogen receptors antigenic site was detected and only seven tumours expressed progesterone receptor in a few cells without any significant clinical value. These results suggest that vessel density is determinant for sporadic acoustic neuroma growth especially for a short clinical course. PMID- 11200591 TI - The endolymphatic sac in patients with Meniere's disease: correlation between the MRI and the surgical findings. AB - The endolymphatic sac (ES) is thought to have close relations to pathogenesis of endolymphatic hydrops. Here is reported a retrospective study of 41 patients (42 ears) with Meniere's disease who underwent MRI prior to endolymphatic sac surgery. Based on proton-density weighted image (PDI) and T2-weighted image (T2), the ES including an endolymphatic duct (ED) were estimated whether it was detectable or not. Fourteen ESs were detected on both images (Group A), 14 ESs were detected only on PDI (Group B), and the remaining 14 ESs were not detected on either image (Group D). The actual shape of the sac, obtained from surgical findings, was classified into three (normoplastic, atrophic, invisible). Seventeen ears showed normoplastic ESs and 14 showed atrophic ESs. ES was not detected in 11 ears during surgery, and these findings were compared with image classification. From the study data, normoplastic ESs tend to be observed on both images whereas atrophic or invisible sacs were hardly observed on T2. This classification of ES on MRI was thought to correlate with surgical findings and this correlation was statistically significant (Spearman's rank correlation coefficient. r(s) = 0.58, p < 0.01). PMID- 11200592 TI - An acoustically evoked short latency negative response in profound hearing loss patients. AB - In our auditory brainstem response (ABR) tests, a peculiar V-shaped negative wave at around 3 4 ms latency was observed. At present, this acoustically evoked short latency negative response (ASNR) is poorly understood. In order to study its appearance and origin, the ABR data of 3104 tests during 1980-98 were reviewed. The ASNR was found only in profound hearing loss ears under intense stimuli (80 120 dB nHL). Out of the total 653 profound hearing loss patients (981 ears), the click-evoked ASNRs were present in 80 patients (12.3%), 117 ears (11.9%). The age range was from 8 months to 70 years. Demographic outcome revealed significant higher appearance rates in young subjects especially in the 20-30 years group. The ASNR was excluded from an artifact by its reproducibility over time, equipment and institutes. Moreover, it became absent after external auditory canal occlusion, which simply blocked the air conduction without any influence upon scalp potentials or equipment. It had neural response characteristics that the latency and amplitude shortened and increased respectively in response to the increase of stimulus intensity. Because the peculiar V-shaped waveform obviously differs from ABR, the ASNR was not interpreted as a potential generated from the conventional auditory pathway. On the other hand, the ASNR individuals were of good vestibular function in sharp contrast with their poor hearing. This suggests the probable relation between the ASNR and the vestibular system. The saccule and vestibular nucleus are hypothesized to be the sense organ and the origin of the response respectively. PMID- 11200593 TI - Regional cerebral blood flow during tinnitus: a PET case study with lidocaine and auditory stimulation. AB - Brain imaging of tinnitus has suggested central correlates of tinnitus perception. This study presents positron emission tomographic (PET) measurements of regional cerebral blood flow (rCBF) in a female tinnitus patient with bilateral left dominant tinnitus. Lidocaine infusion (75 mg during 5 min (0.2 mg/kg/min)) resulted in a 75% reduction of tinnitus and a temporary abolition of the dominant tinnitus in her left ear. Regional CBF was measured in four conditions: i) at rest while concentrating on tinnitus, ii) following maximum effect of lidocaine, iii) during sound stimulation, and iv) the following day at rest while concentrating on tinnitus. Subtraction analyses showed that tinnitus was associated with increased rCBF in the left parieto-temporal auditory cortex, including the primary and secondary auditory cortex with a focus in the parietal cortex (Brodmann areas 39, 41, 42, 21, 22). Activations were also found in right frontal paralimbic areas (Brodmann areas 47, 49 and 15). Sound stimulation resulted in bilateral activation of auditory areas. It is suggested that tinnitus is processed in primary, secondary and integrative auditory cortical areas. Tinnitus perception may involve areas related to auditory attention, while emotional processing relates to temporofrontal paralimbic areas. PMID- 11200594 TI - Relationship between infiltrating cells and adhesion molecules in the nasal mucosa of patients with allergic rhinitis. AB - Antigen-induced changes of cell adhesion molecules and their relationships to infiltrating cells were investigated immunohistochemically in nasal mucosa of perennial allergic rhinitis patients. An increased expression of E-selectin and VCAM-1 was noted on the vascular endothelium of the nasal mucosa 15-25 h after the topical antigen challenge. Although there was no increased expression of ICAM 1, we noted a positive correlation between the expression of E-selectin and ICAM 1. The expression of E-selectin and VCAM-1 as well as ICAM-1 was revealed to be correlated with the number of EG2-positive cells and CD4-positive cells, but not with elastase-positive cells. These findings suggest that all these adhesion molecules play a role in the topical influxes of eosinophils and CD4-positive cells in allergic nasal mucosa. PMID- 11200595 TI - Temperature-controlled radiofrequency tissue volume reduction of the soft palate (somnoplasty) in the treatment of habitual snoring: results of a European multicenter trial. AB - Temperature-controlled radiofrequency tissue volume reduction of the soft palate has been introduced as a minimally invasive, outpatient procedure for the treatment of habitual snoring and mild obstructive sleep apnea. A prospective, non-randomized multi-center European clinical study was conducted to investigate the efficacy of Somnoplasty in reducing snoring. Each patient underwent a pre- and post-treatment full-night polysomnography. TCRFe of the soft palate (1 midline lesion/session) was carried out under local anesthesia with a maximum of 3 consecutive treatment sessions. Forty-five, nonapneic snorers (RDI 5.1 +/- 4.3, BMI 26.6 +/- 3.2 kg/m2) completed the protocol. A mean of 692.3 +/- 67.7) J was delivered/treatment session. There was a significant improvement in the snoring index 7.6 (+/- 2.1 ) vs 4.1 (+/- 2.9). p < 0.001 and in the Epworth Sleepiness Score 8.5 (+/- 5.0) versus 6.0 (+/- 4.3), p = 0.001. No major adverse events were reported and postoperative pain was minimal. Overall, 45% of patients had a post treatment snoring index < 3 (success) and 84% of the patients reported an improvement in snoring. It was concluded that Somnoplasty, following a protocol with I midline lesion of maximal 700 J/lesion for 1-3 treatment sessions, improves snoring in the majority of patients. Further studies are required to investigate whether treatment efficacy can be improved by utilizing multiple lesions/session or by increasing the amount of energy/lesion. The absence of serious adverse events and the findings of minimal postoperative pain support the use of TCRFe (Somnoplasty) as a minimally invasive surgical procedure for snoring. PMID- 11200596 TI - Pain treatment after tonsillectomy: advantages of analgesics regularly given compared with analgesics on demand. AB - The aim of the present prospective study was to evaluate pain treatment during the first postoperative 24 h for 40 patients (age over 18) undergoing tonsillectomy. Patients were divided into two groups: group A (n = 20) received analgesics on demand and group B (n = 20) on a regular basis. Basic pain treatment consisted of paracetamol 750 mg x 6 and diclofenac 50 mg x 3. Pain measurement was performed using a visual analogue scale (VAS): a 10 cm line with 0 cm equalling no pain and 10 cm equalling the worst pain ever felt. The following parameters were studied: VAS values, the need for rescue analgesics, intra- and postoperative bleeding, nausea and vomiting, postoperative food intake and hospital time. Only 4 of 20 (20%) patients in group B needed rescue analgesics in the postoperative ward compared with 15 of 20 (75%) in group A (p < 0.01, chi2 test). In group B, 13 of 20 (65%) patients could eat solid food before they were discharged from the ward, compared with 7 of 19 (37%) monitored patients in group A (p < 0.01, chi2 test). The observed VAS values were generally rather low in both groups. The mean value for all observed VAS values was less than 4 in both study groups. However, no significant difference in VAS values was observed between the two study groups. Our results suggest that regularly given postoperative pain treatment after tonsillectomy, starting intraoperatively with paracetamol and diclofenac, has significant advantages compared with a regimen in which patients receive analgesics only on demand. PMID- 11200597 TI - Upper airway collapsibility in habitual snorers and sleep apneics: evaluation with drug-induced sleep endoscopy. AB - Increased upper airway collapsibility has been suspected of being involved in the pathogenesis of sleep-related diseases. It is assumed that patients with severe obstructive sleep apnea syndrome (OSAS) show a stronger collapse of the upper airway compared with habitual snorers. It was the objective of this study to analyze the patterns of upper airway collapse in habitual snorers and patients with OSAS and to correlate these results with data from polysomnography. Endoscopy was carried out during drug-induced sleep (with propofol) and collapsibility was analyzed at two major levels (palatal and tongue base). A total of 207 habitual snorers and 117 patients with OSAS underwent endoscopy after overnight polysomnography in our sleep laboratory. In 95% of cases we were able to induce snoring during drug-induced sleep. The collapsibility in the area of the base of the tongue correlated with higher values of the respiratory disturbance index (RDI) as recorded by standard polysomnography. Patients with OSAS showed significantly stronger collapsibility compared with snorers. The difference was more evident at the tongue-base level. We found no significant correlation between the applied CPAP pressure and collapsibility in patients with OSAS. These results show that collapsibility at the tongue-base level is a factor relevant in sleep-related breathing disorders. PMID- 11200598 TI - Tympanic neurectomy and chronic parotitis. AB - The preoperative findings and operative outcome were evaluated in 49 patients who underwent tympanic neurectomy to treat chronic parotitis. Forty-two patients had chronic non-suppurative parotitis and 7 patients had chronic suppurative parotitis. The main symptoms prior to operation were recurrent swelling and pain of the parotid gland. After operation, 40 patients (82%) had relief of their symptoms (28 patients were totally free of symptoms and 12 patients were markedly improved). In 9 patients (18%) the symptoms remained the same. Three patients (6%) had a tympanic membrane perforation due to the operation. PMID- 11200600 TI - [Genetic basis for dyslipidemias]. PMID- 11200599 TI - [Lipids, cardiovascular risk factors]. PMID- 11200601 TI - [Oxidized LDL membrane receptors: their role in atherogenesis]. PMID- 11200602 TI - [Atherosclerosis and arteriosclerosis of the small vessels in chronic renal insufficiency and after transplantation: lipid factors]. AB - The prevalence of lipid abnormalities is very high in patients with impaired renal function and after transplantation. Coronary heart disease (CHD) morbidity and mortality are impressive in these patients. No prevention study using lipid lowering agents is available in this population. Thus recommendations are still based on pathophysiological data or extrapolated from the results reported in prevention studies from kidney disease-free subjects. The treatment of hyperlipidemia can be recommended considering the expected reduction of events due to CHD. The lipid targets may be those recommended in other high risk patients: LDL-cholesterol < 120 mg/dl and triglycerides < 150 mg/dl. Unfortunately, the use of both statins and fibrates noteworthy is under restraint in case of renal failure and immunosuppressive therapy. Prospective clinical trials are needed to demonstrate the effect of lipid lowering on the course of chronic renal failure and graft dysfunction. PMID- 11200603 TI - [Atherosclerosis, infection and autoimmunity]. PMID- 11200604 TI - [Lipids, monocytes and progression of renal insufficiency]. PMID- 11200605 TI - [Lipid anomalies during renal insufficiency: consequences on the progression of renal insufficiency and cardiovascular risk]. PMID- 11200606 TI - [Factors in the progression of renal insufficiency other than dyslipidemia]. PMID- 11200607 TI - [Dyslipidemia of diabetes and insulin resistance]. PMID- 11200608 TI - [Atherosclerosis and hemodialysis]. PMID- 11200609 TI - [Evaluation of cardiovascular risk during substitution management: silent cardiopathies]. PMID- 11200610 TI - [Endovascular exploration of the coronary arteries]. PMID- 11200611 TI - [Influence of dialysis membranes on lipid parameters]. PMID- 11200612 TI - [Lipid profiles in peritoneal dialysis]. PMID- 11200614 TI - [Role of lipids in chronic rejection]. PMID- 11200613 TI - [Monitoring of lipid anomalies in renal transplantation]. PMID- 11200615 TI - [Effect of immunosuppressants on lipids]. PMID- 11200616 TI - [ipids and dysfunctional endothelium]. PMID- 11200617 TI - [Statins and cardiovascular disease prevention: use and prospective]. PMID- 11200618 TI - [Treatment of the dyslipidemia of chronic renal insufficiency: respective place of statins and diet]. PMID- 11200619 TI - [Therapeutic management]. PMID- 11200638 TI - [Dependence of oligomerization of influenza virus nucleoprotein on the species affiliation of the virus]. AB - Comparison of human and avian influenza virus nucleoprotein (NP) oligomerization showed that the efficiency of NP oligomerization is different in influenza viruses of different origin. NP oligomerization is virtually complete in avian influenza viruses, while in human influenza viruses only part of monomeric NP is oligomerized. The authors discuss the utilization of NP oligomerization efficiency as a sign for identification of the origin of influenza virus. PMID- 11200639 TI - [Nucleotide sequence of gag and env genes of human immunodeficiency virus type 1, found in Russia: detection of new recombinant variants]. AB - Phylogenetic analysis of nucleotide sequences of gag and env genes of type 1 human immunodeficiency virus (HIV-1) variants isolated from individuals infected through sexual intercourse or nosocomially (by injections with nonsterile syringes) showed that 5 of 27 (18.5%) isolated strains were recombinants. Two viruses found in the Russian Far East had gagAenvE genotype, three other recombinants had envG genotype; gag gene of one isolate belonged to subtype A and gag genes of two others belonged to subtype D. Detection of new recombinant variants in addition to the A/B recombinant described previously shows that these viruses can contribute to the HIV-1 genetic variability in Russia. PMID- 11200640 TI - [Determination of hepatitis G virus markers in various risk groups]. AB - Study of prevalence of hepatitis G virus (HGV) markers in different risk groups showed the presence of HGV RNA in 3.2% blood donors, 24.2% patients with hepatitis C (HCV), and 28% patients with hemophilia. HGV antibodies were detected in 11.3% donors, 16.0% patients with HCV, 13.4% patients with hemophilia, and 8.5% HIV-infected subjects. Anti-E1 HGV were more often detected in the absence of HGV RNA. Antibodies to HGV E2 protein were significantly more often detected in adult HCV patients but not in adolescent patients aged 8-15 years. PMID- 11200641 TI - [Markers of hepatitis C and its various genotypes in patients from Novosibirsk]. AB - Study of the prevalence of hepatitis C virus (HCV) markers in 153 patients of Municipal Infectious Diseases Clinical Hospital No. 1 in Novosibirsk revealed anti-HCV in 88.2% patients and viral RNA in 69.3% samples. For 93 Siberian HCV isolates 5'-UTR regions were amplified and sequenced. Comparison of these nucleotide sequences with databank showed that 63.4% HCV isolates belonged to subtype 1b, 7.5% to genotype 2, and 18.3% to genotype 3. In the rest HCV isolates the 5'-UTR sequences contained heretofore undescribed nucleotide substitutions, insertions, or deletions. PMID- 11200642 TI - [IgM, IgG and IgG subclass antibodies to herpes simplex virus in persons of different ages]. AB - IgM, IgG antibodies to herpes simplex virus and their subclases were investigated in 565 subjects of different age tested at virological laboratories of St. Petersburg in 1996-1997. The majority of these subjects had a history of herpes infection and 21.5% had IgM antibodies to herpes simplex virus (HSV), marker of acute herpetic infection. Besides IgM, IgG1 antibodies can be referred to early antibodies appearing during the acute stage of herpetic infection. The predominant subclass was HSV IgG3 antibodies. As for IgG4, they were completely absent in infants aged under 1 year, were detected in 6.2% children aged under 14 years, and were present in 12.2-12.5% adults. PMID- 11200643 TI - [Production of immune mediators, induced by Lassa virus, in a human mononuclear cell culture]. AB - Infection of human mononuclear cells with Lassa virus leads to production of inflammatory cytokines (tumor necrosis factor and interleukin-1). These cytokines cause expression of adhesion receptors ICAM-1 and VCAM-1 by human endothelial cells. Mitogen-induced cell proliferation was not suppressed 1 h after infection of human mononuclear cells with Lassa virus in a dose of 0.01 PFU/cell. The capacity of cells to proliferation in response to mitogen stimulation decreased significantly only 4 h after infection. PMID- 11200644 TI - [Conformational changes in Lassa viral proteins when exposed to antibodies and complement]. AB - Addition of the complement to the antigen in Lassa virus ELISA stimulated the sensitivity and specificity of the assay. The effect depended on the mouse Ig subclasses. ELISA plate sensitization with IgG2a and IgG2b increased the sensitivity of ELISA 8-16 times. Protein footprinting data suggest that the complement C1q component stimulates antibody-induced conformation changes of the antigen. PMID- 11200645 TI - [Immunogenicity of a recombinant strain of vaccinia virus, expressing a Venezuelan equine encephalomyelitis virus structural protein gene in peroral immunization]. AB - Immunogenicity of recombinant vaccinia virus strain (VR26) expressing Venezuelan equine encephalomyelitis (VEE) virus structural protein genes was studied by oral immunization. Sera of animals immunized with VR26 contained antibodies specific to VEE virus, among which antibodies with virus-neutralizing activity were present. Evaluation of the protective efficiency of oral immunization with VR26 demonstrated a high level of animal protection from lethal doses of VEE virus. Rabbits immunized orally were highly resistant (protection index 142.9) to intranasal infection, which is of priority importance for antiVEE vaccine. Comparative analysis of the results of scarification and oral immunization with VR26 indicates that the type of immune response depends on the method of immunization. These results demonstrate good prospects of oral vaccination with recombinant VR26 strain for immunoprophylaxis of VEE. PMID- 11200646 TI - [Basic results of research on AIDS in 1999]. PMID- 11200648 TI - [Diagnostic possibilities of an immunoenzyme test-system for determining the spectrum of antibodies to structural and nonstructural hepatitis C virus antigens]. AB - A new enzyme immunoassay EIA-HCV-Spectr test system constructed on the base of recombinant proteins and synthetic peptides allows separate detection of antibodies to E1/E2, core, HS3, NS4, and NS5 antigens of hepatitis C virus (HCV). The system is highly specific and more sensitive than the test systems used in screening studies, which allows its use as a final test for antiHCV antibodies. Antibodies to various HCV antigens were analyzed using this test system in patients with acute and chronic hepatitis C and asymptomatic donors with antiHCV. In acute hepatitis C during the first-second week after clinical manifestation, antibodies to nonstructural virus proteins are detected 3-4 times less often than in chronic hepatitis C. Acute hepatitis C is characterized by the presence of antibodies only to core antigen (66%). In chronic condition combinations of antibodies to structural and nonstructural HCV antigens predominate: core + NS4, core + NS3 + NS4, core + NS3 + NS5, core + NS4 + NS5, and core + NS3 + NS4 + NS5. In asymptomatic donors with antiHCV and in patients with chronic hepatitis C the spectra of antibodies were similar in 45.7% cases. PMID- 11200647 TI - [Comparative study of the reactivity, safety and immunogenicity of "Havrix" inactivated hepatitis A vaccine]. AB - This paper sums up the results of controlled field clinical trials of adult and childhood variants of Harvix, inactivated vaccine from hepatitis A. The vaccine is weakly reactogenic and safe. After a single injection of Harvix-1440 vaccine to adults the percentage of seroconversions in previously seronegative individuals was 80.6%, with the mean geometrical antibody titer 119 mIU/ml. In children aged 3-10 years the percentage of seroconversions after a single injection of Harvix-720 vaccine was 100%, the mean geometrical of antibody titer being 427 mIU/ml. Results of laboratory control and field clinical trials recommend both variants of Harvix vaccine for prevention of hepatitis A in the Russian Federation. PMID- 11200649 TI - [Use of in situ hybridization and reverse transcriptase polymerase chain reaction in situ methods for studying infection caused by the hepatitis C virus]. AB - Low level of hepatitis C virus (HCV) replication in hepatocytes does not provide reliable morphological or ultrastructural criteria for detecting an HCV infection by optic and electron microscopy. On the other hand, detection of cellular and subcellular location and tropism of HCV and comparison of virus replication in infected tissues with the level of viremia in patients with hepatitis C require modern methods, combining morphological and molecular biological aspects of diagnosis, such as in situ hybridization (ISH) and reverse transcription polymerase chain reaction in situ (RT-PCR in situ). The target for ISH is HCV RNA, while for RT-PCR in situ it is amplified HCV cDNA, which notably improves the sensitivity of hybridization. PMID- 11200650 TI - [Left ventriculoplasty for non-ischemic cardiomyopathy with severe heart failure in 70 patients]. AB - OBJECTIVES: Treatment of cardiac failure due to non-ischemic cardiomyopathy by left ventriculoplasty using partial left ventriculectomy (Batista operation) or septal anterior ventricular exclusion was evaluated. METHODS: Left ventriculoplasty was performed in 70 patients (59 men and 11 women with a mean age of 51 years) from December 1996 to June 2000. Preoperative New York Heart Association (NYHA) functional class was IV in 43 patients including 29 receiving inotropic support, and class III in 27 patients. Nineteen patients required emergency surgery because of on-going shock and 51 patients were operated electively. Combined cardiac procedures were mitral valve reconstruction in 62 patients (45 replacements, 17 repairs), tricuspid annuloplasty in 37, and aortic valve replacement in 4. The initial 24 patients underwent typical Batista operation regardless of myocardial viability. The other 46 patients underwent selective ventriculoplasty to excise or exclude the weakest part according to the findings of the intraoperative echo-guided volume reduction test. RESULTS: The intraaortic balloon pump was used in 12 patients and the left ventricular assist device in 2 patients. Three (5.9%) of the 51 patients who underwent elective operation and 12 (63.2%) of the 19 patients with emergency operation died in the hospital, giving an overall hospital mortality of 21.4% (15/70). Hospital mortality was reduced from 33.3% (8/24) in the initial 24 patients to 15.2% (7/46) in the recent 46 patients with the volume reduction test. Mean ejection fraction increased from 22.2 +/- 6.7% to 29.6 +/- 6.0%. Diastolic dimension decreased from 81.1 +/- 9.5 to 69.8 +/- 19.2 mm. End-diastolic and systolic volume indices decreased from 199.0 +/- 47.9 to 124.1 +/- 34.9 ml/m2 and from 154.0 +/- 41.2 to 89.3 +/- 31.7 ml/m2, respectively, at one postoperative month in the 55 hospital survivors. The mean pulmonary capillary wedge pressure decreased from 25.6 +/- 7.8 to 13.6 +/- 4.5 mmHg. Serum brain natriuretic peptide decreased from 999 +/- 647 preoperatively to 547 +/- 362 pg/ml one month after the operation. Thirteen patients (18.6%) died in the late period mainly due to heart failure. Among the 42 survivors, 37 patients returned to NYHA functional class I-II, and cardiac events were rare after one postoperative year. Actuarial survivals at 3 years in elective and emergency operations were 71.9% and 33.3%, respectively. CONCLUSIONS: Left ventriculoplasty is acceptably safe for elective operation and clinical improvement can be obtained by proper surgical procedures and careful postoperative medical treatment. PMID- 11200651 TI - Impaired ability to secrete atrial natriuretic peptide in response to isoproterenol infusion in patients with dilated cardiomyopathy. AB - OBJECTIVES: The myocardium has 2 functions in vivo, that of pump and endocrine organ. Therefore, simultaneous examinations of cardiac systolic reserve and endocrine reserve are important in evaluating the activities of the myocardial cells. This study investigated the relationship between cardiac systolic reserve and secretion of atrial natriuretic peptide (ANP) in response to isoproterenol infusion in patients with dilated cardiomyopathy. METHODS: Isoproterenol was infused intravenously in 6 healthy individuals (control group) and 32 patients with dilated cardiomyopathy. The left ventricular systolic responses and plasma ANP concentrations were measured. RESULTS: Patients with dilated cardiomyopathy were classified into 2 groups: patients with a good response (change in fractional shortening > 7%, 17 patients) and those with a poor response (change in < or = 7%, 15 patients). There was no significant difference in end-diastolic dimension, fractional shortening, heart rate, or systolic blood pressure between the 2 groups of patients with dilated cardiomyopathy at rest. The resting plasma ANP concentration in the poor-response group (88.8 +/- 59.0 pg/ml) was significantly higher than that in the other 2 groups (good: 47.0 +/- 35.9 pg/ml, p < 0.05, control: 9.8 +/- 4.1 pg/ml, p < 0.01, respectively). The percentage change in ANP after isoproterenol infusion in the poor-response group (-7.1 +/- 16.7%) was significantly less than that in the other 2 groups (good: 12.6 +/- 27.3%, p < 0.05, control: 31.5 +/- 24.6%, p < 0.01, respectively). CONCLUSIONS: The resting plasma ANP concentration can be used to evaluate the cardiac systolic reserve in patients with dilated cardiomyopathy. Decreased myocardial systolic reserve is also associated with impaired ability to secrete ANP. PMID- 11200652 TI - [Clinical significance of coronary flow reserve in hypertrophied heart: comparison with Doppler index, hemodynamics and plasma natriuretic peptide concentrations]. AB - OBJECTIVES: The relationship was investigated between coronary flow reserve and Doppler echocardiographic parameters, hemodynamic parameters and plasma natriuretic peptide concentrations in the hypertrophied heart. METHODS: The subjects were 19 patients with hypertrophied heart due to various etiologies and no significant coronary artery stenosis. All patients were in sinus rhythm. The left ventricular wall thickness, the E/A ratio in transmitral flow velocity pattern and the Doppler index were determined by Doppler echocardiography, and the plasma atrial and brain natriuretic peptide concentrations were measured. At cardiac catheterization, pulmonary capillary wedge pressure and left ventricular end-diastolic pressure were measured, and the coronary flow reserve was obtained by injecting intracoronary adenosine triphosphate into the left anterior descending artery using a Doppler guidewire. RESULTS: Coronary flow reserve in the patients was significantly lower than in 11 normal control subjects (2.50 +/- 0.76 vs 3.90 +/- 0.64, p < 0.001). There were no significant correlations between coronary flow reserve and the left ventricular wall thickness or the E/A ratio. The mean value of the Doppler index in the patients was 0.48 +/- 0.10 and there was a significant negative correlation between coronary flow reserve and the Doppler index (r = -0.73, p < 0.001). The correlation between coronary flow reserve and left ventricular end-diastolic pressure was not significant, but there was a significant negative correlation between coronary flow reserve and pulmonary capillary wedge pressure (r = -0.64, p < 0.01). There were significant negative correlations between coronary flow reserve and atrial (r = -0.62, p < 0.01), or brain natriuretic peptide concentrations (r = -0.56, p < 0.05). CONCLUSIONS: Coronary flow reserve may reflect overall cardiac performance evaluated by the Doppler index and plasma natriuretic peptide concentrations in the hypertrophied heart, and the measurement of coronary flow reserve may be useful for evaluating disease severity in patients with hypertrophied heart. PMID- 11200653 TI - [Effects of cilostazol in patients with bradycardiac atrial fibrillation]. AB - OBJECTIVES: Cilostazol, an antithrombotic agent, directly and indirectly increases the heart rate. This study investigated whether cilostazol increases the heart rate, and whether it has chronotropic effects on cardiac failure in patients with bradycardiac atrial fibrillation. METHODS: Twelve patients (6 males and 6 females) with bradycardiac atrial fibrillation underwent Holter monitoring (24-hour total heartbeat counts and frequency of pause), echocardiography (left ventricular end-diastolic diameter, percentage fractional shortening), chest roentgenography (cardiothoracic ratio), and measurements of brain natriuretic peptide and atrial natriuretic peptide before and 6 months after daily oral administration of 100-200 mg cilostazol. RESULTS: Cilostazol administration increased the 24-hour total heartbeat counts from 69,685 +/- 1,690 (mean +/- SE; mean heart rate: 48 beats/min) to 87,352 +/- 3,123 (60), and decreased the frequency of pause from 362.3 +/- 72.9 to 112.3 +/- 41.0. Cardiothoracic ratio decreased from 55.8 +/- 1.1% to 52.5 +/- 1.1%, left ventricular end-diastolic diameter from 56.1 +/- 0.9 to 52.9 +/- 0.8 mm, but percentage fractional shortening was not significantly changed (from 33.0 +/- 2.2% to 33.7 +/- 2.1%). Brain natriuretic peptide decreased from 97.9 +/- 20.5 to 33.5 +/- 4.8 pg/ml, and atrial natriuretic peptide from 69.5 +/- 12.1 to 46.7 +/- 8.3 pg/ml. CONCLUSIONS: Cilostazol has beneficial effects in patients with bradycardiac atrial fibrillation. The increase of heart rate may be mediated by improvement of conductivity in the atrioventricular node and increase of coronary blood supply caused by dilation of vessels. PMID- 11200654 TI - [Clinical validation of accuracy of anatomical M-mode measurements: effect of harmonic imaging]. AB - OBJECTIVES: Recent advances in ultrasound technology allow reconstruction of images from stored radiofrequency information and creating of M-mode echocardiograms along an M-mode cursor of any direction (anatomical M-mode echocardiography). METHODS: The accuracy of the measurements obtained by anatomical M-mode echocardiography was evaluated by comparing the measurements with those by B-mode echocardiography with or without harmonic imaging in 8 normal subjects and 14 patients with cardiac disorders. Measurements used the left ventricular short-axis image in 4 different directions (0 to 6, 3 to 9, 1 to 7 and 5 to 11 o'clock). RESULTS: Anatomical M-mode and B-mode measurements showed good linear relationships with correlation coefficients of 0.90 to 0.99 in any of the 4 directions. However, measurements in the lateral direction (3 to 9 o'clock) showed larger errors than those in the other directions (p < 0.05). With the use of harmonic imaging, the errors tended to become smaller, although it did not reach statistical significance. CONCLUSIONS: Anatomical M-mode echocardiography accurately measures the left ventricular internal diameter in any direction except the lateral direction. Harmonic imaging is useful to decrease the errors. PMID- 11200656 TI - [On the occasion of the 30th anniversary of the Japanese College of Cardiology]. PMID- 11200655 TI - [Mitral valve tumor incidentally found after cerebral infarction]. PMID- 11200657 TI - [Japanese College of Cardiology in the 20th century and hopes for the 21st century]. PMID- 11200658 TI - [Acetyl starch as volume substitute, a possible alternative to HES]. AB - OBJECTIVES: Pharmacokinetics and tolerability of acetyl starch (ACS) in comparison to hydroxyethyl starch (HES) were investigated after repeated intravenous infusions. METHODS AND COHORTS: A 500 ml solution of ACS (n = 8) or HES (n = 9) was infused to male volunteers (Age 25-42 Years) over four hours on five consecutive days. RESULTS: Comparing the pharmacokinetic parameters, marked differences were found between ACS and HES. A continuos increase of Cmax, AUC0-24 and t1/2 over the five days caused by administration of HES was due to an accumulation of HES in serum. However, after administration of ACS all these parameters remained unaltered. The repeated infusion of 50 g ACS did not cause any changes of the acid-base-status. The influence of ACS on the coagulation parameters was comparable to that of HES and due to dilution effects. The acetic acid concentration increased up to 2.96 +/- 0.67 mg/dl following ACS infusion. The blood glucose concentration was not influenced by the infusion of HES or of ACS. The repeated ACS infusions were well tolerated. In contrast to HES, ACS did not accumulate in serum. CONCLUSION: According to these data ACS is an alternative to HES for volume replacement. Well-known side effects due to long storage of HES in tissues may not occur following application of ACS. However, the wide usage of ACS is restricted by the limited stability of ACS solutions at room temperature. ACS solutions are thus only stable during storage at lower temperatures. PMID- 11200660 TI - [Oral rapid desensitization with rifampicin]. PMID- 11200659 TI - [Solitary fibrous thoracic wall tumor. Progression with percutaneous radiotherapy]. AB - HISTORY AND CLINICAL FINDINGS: A 81-year-old patient free of pain was referred to the university hospital for further evaluation and therapy of tumour masses in the right thorax. Clinical examination revealed dullness to percussion and reduced breathing in the right lower lung. INVESTIGATIONS: Computed tomography showed an enlarged solid tumour mass attached to the thoracic cavity and pleural effusion on the right side. Quantification of pulmonary perfusion presented significant defects in the right upper and middle lobe. DIAGNOSIS, TREATMENT AND COURSE: The pulmonary masses were biopsied under CT-guidance. Biopsy and immunohistochemical findings proved a malignant solitary fibrous tumour of the chest wall, a mesenchymal tumour of its own entity. Because of pain in the right arm and because of missing other reliable therapeutic options a palliative irradiation was performed. The tumour did increase in size due to radiotherapy and a severe right ventricular heart failure occurred. The patient died 5 months after diagnosis has been made. Autopsy revealed a transition of tumour cells to sarcomatic growth. CONCLUSION: In our case we conclude an accelerated progression of the solitary fibrous chest wall tumour in the course of irradiation. Whether the development of sarcomatic growth occurred as a result of radiotherapy remains speculative. PMID- 11200661 TI - [Polygene diseases: use of inbred mice for identification of disease-relevant genes]. PMID- 11200662 TI - [Diagnosis of cystic echinococcosis]. PMID- 11200663 TI - [Treatment of risk factors in primary prevention of cerebral ischemia]. PMID- 11200664 TI - [Forfeit of future reimbursement requests by patients from private health insurance]. PMID- 11200665 TI - [Iodine deficient diet?]]. PMID- 11200666 TI - [Life threatening hypercalcemia in a young man with ALL]. AB - HISTORY AND ADMISSION FINDINGS: A 16-year-old man experienced fatigue, vomiting and diffuse abdominal pain. Since 4 days he had myalgia in both arms and legs. On examination only a tachycardia of 110/min was noticed. INVESTIGATIONS: Laboratory tests revealed hemoglobin 12.7 g/dl, leucocytes 10,300/microliter, platelets 89,000/microliter, LDH 191 U/l, sodium 134 mmol/l, potassium 2.76 mmol/l, calcium 4.52 mmol/l (I), creatinine 1.13 mg/dl, urea 72 mg/dl, uric acid 11.2 mg/dl. The levels of PTH (0 pg/ml), PTH-related peptide, vitamin D, vitamin A, IGF-1, STH, 5 HIES and interleukin 6 were within normal limits. TNF-alpha 25.9 pg/ml (< 8.1). The electrocardiography revealed a sinus rythm with a QT-time of 0.28 s (= 100%). Multiple osteolytic bone leasions were seen in thoracic CT-scan. Abdominal sonography showed normal liver structure, multiple subhepatic lymph nodes without splenomegaly. The cytologic examination of the bone marrow demonstrated a diffuse infiltration by a common acute leukemia. TREATMENT AND COURSE: The rehydration with physiologic saline (3500 ml/d) was initiated in the ICU. Furosemide was added for further renal excretion. Additionally prednisone (100 mg/d) and calcitonin (300 I.E./d) were given. The calcium level fell within two days. No cardiac arrhythmia nor acute renal failure were seen. After definitive diagnosing the patient was treated corresponding to a specific protocol. One year later the relapsing ALL was diagnosed also by hypercalcemia (5.9 mmol/l). The level of TNF alpha before and after correction of hypercalcemia was 20 pg/ml. CONCLUSION: The acute treatment of hypercalcemia is independent of the underlying cause (rehydration with physiologic saline, renal excretion with furosemide, inhibition of osteoclastic activity). The main causes are hyperparathyreoidism or malignancys (90%). We describe TNF-alpha as a possible marker of tumoral load of a common ALL but we are not able to reveal a correlation between TNF-alpha and the calcium level. PMID- 11200667 TI - [AIDS--no magic (healing) in sight]. PMID- 11200668 TI - Isolation and characterization of beta-galactosidase from Lactobacillus crispatus. AB - beta-Galactosidase was isolated from the cell-free extracts of Lactobacillus crispatus strain ATCC 33820 and the effects of temperature, pH, sugars and monovalent and divalent cations on the activity of the enzyme were examined. L. crispatus produced the maximum amount of enzyme when grown in MRS medium containing galactose (as carbon source) at 37 degrees C and pH 6.5 for 2 d, addition of glucose repressing enzyme production. Addition of lactose to the growth medium containing galactose inhibited the enzyme synthesis. The enzyme was active between 20 and 60 degrees C and in the pH range of 4-9. However, the optimum enzyme activity was at 45 degrees C and pH 6.5. The enzyme was stable up to 45 degrees C when incubated at various temperatures for 15 min at pH 6.5. When the enzyme was exposed to various pH values at 45 degrees C for 1 h, it retained the original activity over the pH range of 6.0-7.0. Presence of divalent cations, such as Fe2+ and Mn2+, in the reaction mixture increased enzyme activity, whereas Zn2+ was inhibitory. The Km was 1.16 mmol/L for 2-nitrophenyl-beta-D galactopyranose and 14.2 mmol/L for lactose. PMID- 11200669 TI - Effect of the carbon source on assessment of degrading bacteria with the spread plating technique during in situ bioremediation. AB - Spread-plating belongs to traditional microbiological methods employed for quantification of subsurface microflora during bioremediation projects in the Czechia. Concentration of degrading organisms is estimated from the number of colonies grown on agar plates supplied with contaminant as the sole carbon source. The data obtained during in situ bioremediation of the Dacice site contaminated by cutting oil suggests that changes in the composition of the carbon source in the subsurface may cause a discrepancy between laboratory data and situation in subsurface. PMID- 11200670 TI - Effects of increasing doses of UV-B radiation on photosynthesis and motility in Chlamydomonas reinhardtii. AB - Effects of increasing doses of UV-B radiation on photosynthetic efficiency (PE) and motility in Chlamydomonas reinhardtii were investigated. The exposure time ranged from 10 to 120 min at 0.73 W/m2 UV-B radiation. A decrease in compensation points (CP) was followed by an increase in PE on extending the UV-B treatment up to 60 min. The subsequent increase in PE was accompanied by increasing CPs. Enhanced doses of UV-B radiation thus have a stimulatory effect on the PE in C. reinhardtii. No inhibitory effects could be detected. No statistically significant differences in motility could be observed due to an extremely high variation of values. PMID- 11200671 TI - Postantibiotic effects of gentamicin and netilmicin on Serratia marcescens: effects on hydrophobicity and motility. AB - The impact of postantibiotic effect (PAE) of aminoglycosides (gentamicin, netilmicin) on cell-surface hydrophobicity and motility of a clinical isolate Serratia marcescens was evaluated. For the induction of PAE 2x and 4xMIC concentrations of both antibiotics were used. Gentamicin and netilmicin induced a PAE of similar duration after 2xMIC concentration (2.7 and 2.8 h, respectively). Both aminoglycosides demonstrated concentration-dependent PAE. At a concentration of 4xMIC they produced PAEs of 5.9 and 8.2 h, respectively. The evaluation of hydrophobic properties of S. marcescens after affecting PAE showed that both aminoglycosides inhibited adherence to xylene. This inhibition was also concentration-dependent. More expressive was netilmicin which inhibited the adhesion by 70.5% at 2xMIC and by 85.2% at 4xMIC. Netilmicin inhibited also the adhesion to nitrocellulose filter by 34.7% at 4xMIC. Exposure of the bacterial cells to suprainhibitory concentrations of both aminoglycosides resulted only in moderate inhibition of motility of strain tested compared to the unexposed cells. PMID- 11200672 TI - Induction of colony morphology variation in Rhodotorula gracilis by UV irradiation. AB - Nonlethal UV irradiation induced an unusually high frequency of colony morphology variation in Rhodotorula gracilis. The variation was not fixed but indicated further variability in subsequent platings. Microscopic examination of the cultures indicated that UV-irradiated variants had grossly varying types of shapes and arrangements of cells in contrast to the uniformly shaped and budding cells of the nonirradiated culture. Flow-cytometric analysis of a colony variant suggested a slightly higher proportion of cells with variable DNA content than the nonirradiated culture. Extensive biochemical characterization revealed only one difference in that the nonirradiated culture had a partial requirement for pantothenate while the colony variant was completely independent of this requirement. We speculate that UV triggers a yet unstudied means of variability in R. gracilis with possible accompanying recombinational events. PMID- 11200673 TI - Immunoelectrophoretic analysis of medium-derived antigens bound to the surface of Mycoplasma hominis, Mycoplasma fermentans and Ureaplasma urealyticum. AB - We analyzed Mycoplasma hominis, Mycoplasma fermentans and Ureaplasma urealyticum antigens by immunochemical methods. The immunochemical reaction showed that all three species bound to the surface of one medium component, which origin stemmed from the horse serum. This substance functioned as one of the most potent components of mycoplasma immunogens for all three species. PMID- 11200674 TI - Detection of coxsackie B virus infection using a rapid screening method. AB - A Western blot method (WB) was adapted for rapid screening of antibodies against coxsackie virus B1-B6 in sera from patients with newly diagnosed insulin dependent diabetes mellitus, myocarditis or febrile syndrome of suspected coxsackie viral aetiology. The use of a mixture of all 6 coxsackie virus B serotypes as the common antigen permitted a very rapid and inexpensive detection of antibody-positive sera for preliminary diagnosis and further detailed assay. Comparison of the results with those obtained in parallel run virus neutralization tests showed a higher sensitivity and comparable specificity of WB. PMID- 11200676 TI - Loss of virus specific epitopes on JE virus 'E' glycoprotein by acetone treatment. AB - BACKGROUND & OBJECTIVES: Some Japanese encephalitis (JE) virus strains have been placed in group II based on the loss of reactivity against Hs (H = HI positive; s = JE virus specific) group of monoclonal antibodies (MAbs) in haemagglutination inhibition (HI) test employing sucrose acetone (SA) extracted antigens. Also acetone-fixation of cells infected with some of the virus strains results in the loss of immunofluorescence (IF) against virus specific MAbs. The present study was undertaken to elucidate the effect of acetone on virus specific haemagglutination (HA) epitopes expressed on 'E' glycoprotein of group II strains of JE virus. METHODS: Porcine kidney (PS) cells were infected with JE virus strains (2 group I Indian strains, 5 group II strains and one neutralization escape variant of 733913 group I strain). HI and complement fixation (CF) tests were carried out employing both polyethylene glycol (PEG) precipitated and SA extracted antigens of JE virus. RESULTS: Employing PEG precipitated antigens, Indian strain G9473 showed titres ranging from 1:40 to 1:160 against all the four virus specific HsMAbs and strain 641686 (1:160) with one of the four MAbs (Hs-1) by HI test whereas their SA extracted antigens did not react at all. In contrast, CF was positive employing both SA and PEG antigens in the presence of all four HsMAbs. The reactivity shown by PEG antigens in the HI test was confirmed by blocking the HA activity with the respective MAb. SA antigens, though negative in the HI test, were positive by the blocking assay. Interestingly, some of the non HI MAbs which were negative against SA antigens, showed positive HI reaction with PEG antigens. Also, additional epitopes on Japanese (Yoken), Sri Lankan (691004) and two Indian (755468 and 641686) JE virus strains were detected either by blocking HA or surface IF. INTERPRETATION & CONCLUSIONS: It seems that the acetone treatment might result in HA property of the antigen which is no longer inhibited by an antibody in the HI test. The characterization of such labile and conformation-dependent epitopes is currently been undertaken to elucidate their role either in protection or immunopathogenesis of JE. PMID- 11200677 TI - Clinical implications of hepatitis G virus (HGV) infection in patients of acute viral hepatitis & fulminant hepatic failure. AB - BACKGROUND & OBJECTIVES: Viral hepatitis is a major public health problem especially in developing countries such as India. Hepatitis viruses A, B, C, D and E are all well characterized and molecularly defined agents with unequivocal association with human liver disease but there is evidence of hepatitis in humans caused by certain transmissible agents which cannot be classified with the above hepatotoric viruses. The role of recently discovered hepatitis G virus (HGV/GBV C) as an independent heaptitis agent is controversial. Recently, we have shown a relatively high frequency of HGV infection in fulminant hepatic failure but the virus was often detected in co-infection with hepatitis B or E virus. The present study has therefore been carried out to evaluate the clinical significance of HGV infection in acute viral hepatitis (AVH) and fulminant hepatic failure (FHF) through follow up of HGV positive patients till their clinical and biochemical recovery. METHODS: The study included 50 patients comprising 35 of AVH and 15 of FHF. These patients were evaluated on the basis of history, physical examination, liver function profile and serological markers for hepatitis A, B, C and E. Those patients serologically negative for HBV and HCV infection were further screened for HBV DNA and HCV RNA by PCR. All the samples were screened for presence of HGV RNA by RT-PCR using inner and outer primers sequences selected from NS3 helicase region of the HGV genome. FHF patients who died were subjected to postmortem liver biopsy and these biopsy specimens were also screened for HGV-RNA. Repeat detection of HGV-RNA was done after clinical and biochemical recovery of the patients. RESULTS: Of 35 AVH patients, HGV infection was detected in 5 patients (14.3%) while 4 of 15 patients (26.6%) in the FHF group were positive for HGV RNA. Five HGV positive AVH patients were followed till clinical and biochemical recovery and all of them tested positive for HGV-RNA at follow up (6 weeks to 6 months). Out of 4 HGV positive FHF patients, only one survived and his repeat sample after clinical and biochemical recovery tested positive for HGV-RNA. INTERPRETATION & CONCLUSIONS: The results suggest that HGV infection does occur in patients of AVH and FHF and HGV viraemia persists for a long time even after clinical and biochemical recovery. These observations point towards a possible non-pathogenic role of hepatitis G virus infection. PMID- 11200678 TI - Analysis of serological evidence of different hepatitis viruses in acute viral hepatitis in prisoners in relation to risk factors. AB - BACKGROUND & OBJECTIVES: The present study describes an outbreak of acute viral hepatitis in an institutional population (inmates of a prison) with an aim to delineate the etiological agents of this outbreak and to analyse the clinical, biochemical and serological evidence of different hepatitis viruses in relation to risk factors. METHODS: Fifty patients of acute viral hepatitis identified during the outbreak were evaluated on the basis of history, clinical examination, risk factor distribution, biochemical profile and serological markers for hepatitis A-E infection. Adequate epidemiological data were collected from prison administration including housing of prisoners, food and water supply. RESULTS: Of the 50 patients, 35 (70%) had serological evidence of HEV infection. Evidence of HBV infection was found in 17 patients (34%), HAV infection in 2 (4%) and HCV in 8 (16%) patients. While 16 patients (32%) had evidence of multiple viral infections, none of the viral markers could be detected in 8 patients (16%). One or more risk factor(s) could be identified in more than half of the subjects (26/50; 52%). There were 11 patients who gave history of more than one risk factor while 24 (48%) patients had none of the risk factors. INTERPRETATION & CONCLUSIONS: HEV was found to be the major cause of the outbreak and contamination of drinking water supply could be the possible source of infection. This outbreak was seroepidemiologically similar to other outbreaks of hepatitis occurring in the country with HEV being the most common cause. However, there was evidence of multiple viral infections, particularly HBV and HCV in the high-risk predisposed prison population. PMID- 11200679 TI - Enteroaggregative Klebsiella pneumoniae in association with childhood diarrhoea. AB - A total of 19 strains of Klebsiella pneumoniae isolated as sole pathogen from children with diarrhoea were used to study their virulence mechanism using different assays. Eith strains of K. pneumoniae exhibited aggregative adherence that was distinct from the stacked brick enteroaggregative pattern shown by Escherichia coli. The study suggests the presence of a new virulence mechanism in the pathogenesis of Klebsiella-associated diarrhoea. PMID- 11200680 TI - Prevalence of Trichuris trichiura in relation to socio-economic & behavioural determinants of exposure to infection in rural Assam. AB - BACKGROUND & OBJECTIVES: Stunting, anaemia, and the poor level of mental development are known to be associated with Trichuris trichiura infections. However, no information is available on the socio-environmental predictors relevant to Trichuris infection in rural communities. Whilst geohelminthic infections per se is an inevitable consequence of poor personal hygiene and household sanitation, the importance of specific factors in the epidemiology of Trichuris infection have not been formally investigated. The objective of this study was to explore, quantify and study different socio-environmental risk factors and find out their possible interaction vis-a-vis T. trichiura infection. METHODS: The study population consisted of 244 children (aged 15 yr and below) and 336 adults selected from 144 randomly selected households belonging to three villages of upper Assam. The prevalence rate ratio (PRR; = relative risk) and 95 per cent confidence interval (CI) were calculated. Univariate, multivariate analysis using Cox's proportional hazards regression assuming constant risk period and a tree-based risk factor analysis, were used. RESULTS: In the overall multivariate model, open field defaecation, large family size, and three or more children in the household were found independently associated with Trichuris infection. Gender specific analysis revealed that in females the age was also independently associated with increased risk of infection whereas in males, earth flooring was the most significant risk factor independently associated with the risk of Trichuris infection. Tree-based risk factor analysis indicated interaction between defaecating habits of people and the source of drinking water. INTERPRETATION & CONCLUSIONS: Installation of pit latrines (if not sanitary latrines) together with provision for safe drinking water and the construction of cement floors would probably reduce community prevalence of T. trichiura effectively. PMID- 11200675 TI - Early expression of herpes simplex virus (HSV) proteins and reactivation of latent infection. AB - During the last decade, new data accumulated describing the early events during herpes simplex virus 1 (HSV-1) replication occurring before capsid formation and virion envelopment. The HSV virion carries its own specific transcription initiation factor (alpha-TIF), which functions together with other components of the cellular transcriptase complex to mediate virus-specific immediate early (IE) transcription. The virus-coded IE proteins are the transactivator and regulatory elements modulating early transcription and subsequent translation of nonstructural virus-coded proteins needed mainly for viral DNA synthesis and for the supply of corresponding nucleoside components. They also cooperate at the late transcription and translation of the virion (capsid, tegument and envelope) proteins. In addition, the transactivator IE proteins down-regulate their own transcription, while others facilitate viral mRNA processing or interfere with the presentation of newly synthesized virus antigens. Establishment of latency is closely related to the transcription of a separate category of transcripts, termed latency-associated (LAT). Formation of LATs occurs mainly in nondividing neurons which are metabolically less active and express lower levels of cellular transcription factors (nonpermissive cells). Expression of the stable non-spliced (2 kb), and especially of stable spliced (1.5 and 1.45 kb) LATs is a prerequisite for HSV reactivation. Different HSV genomes (from various HSV strains) do not undergo IE transcription at the same rate. Restricted IE transcription and the absence of viral DNA synthesis favors LAT formation and persistence of the silenced genome. Uneven levels of LAT expression and differences in the metabolic state of carrier neurons influence the reactivation competence. Under artificial or natural activation conditions, sufficient amounts of IE transactivator proteins and proteins promoting nucleoside metabolism are synthesized even in the absence of the viral alpha-TIF facilitating reactivation. PMID- 11200681 TI - [Genetics and urology]. PMID- 11200682 TI - Truth and consequences. PMID- 11200683 TI - Dilemmas in the management of patients with arteriovenous malformations. AB - An arteriovenous malformation (AVM) consists of one or more arteries that drain through one or several small openings directly into one or more veins. The capillary system between arteries and veins is missing. The natural history of an unruptured AVM demonstrates a 1-2% bleeding rate and once ruptured a 2-4% annual risk of rebleeding. There is a risk of dying of AVM up to 1% per year, a 1% annual risk of developing de novo epilepsy, and a 1% chance of disability per year. Small AVMs are more likely to rupture than large AVMs. The goal of treatment is complete obliteration of the malformation. The risk of surgical treatment depends mainly on its size, location and drainage pattern. Size and angioarchitecture determine the risks of embolotherapy and radiotherapy. AVMs in Spetzler-Martin grades I-III should be treated by microneurosurgery or a combination of embolotherapy and microneurosurgery. They can be excised with low surgical mortality and morbidity. For AVMs in Spetzler-Martin grades IV and V staged treatment approaches such as embolotherapy followed by surgery or radiotherapy should be considered. Rarely is embolotherapy or radiotherapy alone indicated. There are AVMs in Spetzler-Martin grades IV and V that may be inaccessible for surgical or any other treatment, and that should be left alone. Prospective randomised trials on the optimal management of AVMs are lacking. All our knowledge on AVMs stems from open series and indirect comparisons. PMID- 11200684 TI - Creutzfeldt-Jakob disease: heat shock protein 70 mRNA levels in mononuclear blood cells and clinical study. AB - Prion diseases such as Creutzfeldt-Jakob disease (CJD) are associated in most cases with the accumulation of an unusual isoform of prion protein (PrPSC). PrPSC is derived from the abnormal folding of the cellular isoform of prion protein (PrPC). On the other hand, heat shock protein is known to ensure proper protein assembly and folding and to facilitate proteolytic digestion of abnormal or denatured proteins. Many studies have therefore hypothesized that heat shock protein is linked to prion disease. We examined the relationship between heat shock protein HSP70 and prion disease in CJD patients. HSP70 mRNA levels in mononuclear blood cells (MBCs) were compared in 14 CJD patients (10 confirmed by histo-pathological study), 12 vascular dementia (VD) patients, 16 patients with Parkinson's disease and dementia (PD) and 14 nondemented control subjects. The possible correlation between HSP70 mRNA expression levels and clinical findings was also evaluated. HSP70 mRNA expression levels in MBCs were measured by northern blotting. HSP70 mRNA levels in MBCs from patients with CJD were significantly higher than those from patients with VD or PD and in nondemented controls. Age at symptom onset, dementia severity, disease duration and neuroimaging grade of CJD patients were not correlated with relative HSP70 mRNA levels. No significant relationship between HSP70 mRNA levels and ageing was found. These results suggest that measurement of HSP70 mRNA in MBCs might provide an auxiliary tool for the diagnosis of CJD. PMID- 11200685 TI - Anti-alpha B-crystallin immunoreactivity in inflammatory nervous system diseases. AB - alpha B-Crystallin, a small heat shock protein, is an immunodominant antigen with increased tissue expression in demyelination. To investigate the humoral response against alpha B-crystallin, the sera and CSF samples of patients with multiple sclerosis (MS), Guillain-Barre syndrome (GBS), neuro-Behcet's disease (NBD) and other non-inflammatory neurological diseases (NIND) were screened by enzyme linked immunosorbent assay for anti-alpha B-crystallin IgG and IgM antibodies. Serum and CSF IgG antibody responses to alpha B-crystallin were significantly elevated only in NBD patients (serum IgG, NBD 1.29 +/- 0.49 vs. NIND 0.95 +/- 0.39, P = 0.01; CSF IgG, NBD 1.22 +/- 0.64 vs. NIND 0.81 +/- 0.35, P = 0.01). Similarly, high serum IgM antibody titres were also detected in NBD (1.83 +/- 0.72 vs. 1.16 +/- 0.49, P = 0.0005) and in MS (1.57 +/- 1.07, P = 0.046), whereas elevated CSF IgM responses were observed only in GBS (2.09 +/- 1.09 vs. 1.41 +/- 0.7, P = 0.007). Humoral responses against alpha B-crystallin are increased in NBD and GBS, which may implicate this central nervous system antigen in the causation and pathogenesis of these inflammatory nervous system disorders. PMID- 11200686 TI - Genotyping of presenilin-1 polymorphism in amyotrophic lateral sclerosis. AB - The mechanisms underlying motor neuron degeneration in amyotrophic lateral sclerosis are not fully understood. Recent studies suggest that apoptosis is involved in the abnormal neural death that occurs in this devastating disease. Presenilin-1, a transmembrane protein, seems to be implicated in apoptosis. To determine whether presenilin-1 intron 8 polymorphism has an influence in the course of amyotrophic lateral sclerosis, we examined this polymorphism genotypes in a large group of patients (n = 72) with amyotrophic lateral sclerosis and in a random sample of 213 healthy individuals. The results showed a significant difference in genotype (P < 0.04) and allele (P < 0.03) distribution between patients controls. These results suggest a possible intervention of presenilin-1 in the pathogenesis of amyotrophic lateral sclerosis. PMID- 11200687 TI - Neurophysiological studies in acute transverse myelitis. AB - A systematic evaluation of anterior horn cell, motor and sensory pathways is possible by electromyography (EMG), motor (MEPs) and somatosensory (SEPs) evoked potentials, respectively, which may provide valuable information on acute transverse myelitis (ATM). In a prospective hospital-based study, EMG, MEP and SEP studies were carried out on admission and after 3 months in 39 patients with ATM. All the patients also underwent detailed clinical evaluation, and spinal magnetic resonance imaging (MRI) was performed in 28. Outcome was defined at the end of 3 months as poor, partial or complete recovery on the basis of functional status. Spinal MRI revealed hyperintense signal changes in T2 extending for two segments to the entire spinal cord. Central motor conduction time to tibialis anterior (CMCT-TA) was more frequently abnormal (90%), followed by tibial SEP (77%). CMCT to abductor digiti minimi (ADM) was abnormal in 30% and median SEP in 15% of patients. Evidence of denervation on EMG was present in 51% of patients. The CMCT-TA improved in 48% patients and tibial SEP in 32%. Median SEP improved in all patients, and CMCT-ADM remained prolonged in two. At 3 months 2 patients had died, and 18 had poor, 10 partial and 9 complete recovery. CMCT was correlated with muscle power, tone, reflex and MRI changes. Patients' outcome of was correlated with CMCT, SEP and EMG. These results are consistent with pronounced involvement of dorsal region of spinal cord in ATM. MEP is more frequently abnormal than SEP. PMID- 11200688 TI - Acute-onset painful upper limb multifocal demyelinating motor neuropathy. AB - We report three patients who presented with acute onset of shoulder and upper arm pain followed within a few days by predominantly distal upper limb weakness. Nerve conduction studies showed severe and unequivocal focal motor conduction block in the forearm and/or upper arm along with slowing of motor conduction and prolonged F wave responses. Only very mild changes in sensory nerve conduction were found. One patient made partial clinical improvement after 17 months, and there was a significant improvement in the degree of motor conduction block and the motor conduction velocities. A second patient remained unchanged after 5 months. Idiopathic brachial neuritis (IBN) typically presents acutely with brachialgia and acute or subacute non-progressive weakness. Multifocal motor conduction block in nerves in the arm or forearm has not been described in patients with IBN. Multifocal motor conduction block restricted to the upper limbs has been described in focal chronic inflammatory demyelinating polyneuropathy (CIDP) and in multifocal motor neuropathy with multifocal motor conduction block (MMNCB). However, both these conditions have hitherto usually been described as largely painless chronic progressive disorders with a subacute onset. Our patients, with features overlapping MMNCB/CIDP and IBN, represent an as yet unreported clinical variant. PMID- 11200689 TI - Essential tremor: an overdiagnosed condition? AB - The diagnosis of essential tremor (ET) and its differentiation from other types of tremor is often difficult. In 1994 Bain et al. defined a classical phenotype by studying 20 patients with pure essential tremor and similarly affected family members in at least three generations. We assessed how many of the patients diagnosed by different neurologists at our institution as having ET conformed to this defined phenotype. We randomly selected 50 patients who were diagnosed with ET by any neurologist at the National Hospital for Neurology and Neurosurgery since the publication of the Bain et al. report, and determined the number of patients who had clinical features compatible with the phenotype that it had defined. Only 25 (50%) of these patients had ET so defined. Ten patients clearly had alternative diagnoses: four had clear additional dystonia, two neuropathic tremor, two had unilateral leg tremor, one drug-induced tremor, and one sudden onset after head trauma. The remaining 15 patients also had atypical features including myoclonus (one), onset in a body part other than the arms (six), sudden onset (two), rest tremor (seven), onset after the age of 65 years (four), a family member with an isolated head tremor (one), or reduced armswing (two). The diagnosis of ET is overused even among experienced neurologists, and other types of tremor should be considered in atypical patients before making this diagnosis. PMID- 11200690 TI - Sensitivity and reproducibility of volume change measurements of different brain portions on magnetic resonance imaging in patients with multiple sclerosis. AB - The course of multiple sclerosis (MS) can be monitored by measuring changes in brain volume, but consensus is still lacking on the best strategy to be adopted. We compared the reproducibility and sensitivity of volume measurements from different brain portions for detecting changes on magnetic resonance imaging (MRI) in patients with MS. T1-weighted MRI of the brain was performed in 50 patients with relapsing-remitting MS at study entry and after an average follow up of 18.4 months. Using a semiautomated technique for brain parenchyma segmentation, the volumes of the following brain portions were measured: (a) the whole brain (whole-brain volume, WBV), (b) the seven slices rostral to the velum interpositum (seven-slice volume, SSV), (c) the central slice of the image set (central-slice volume, CSV) and (d) the infratentorial regions (infratentorial brain volume, IBV). All these measurements were carried out by a single observer and were repeated twice on ten randomly selected scans to test the intra-observer reproducibility using the four strategies. At follow-up there was a significant decrease in all the measures of brain volume (P ranged from 0.002 to < 0.001). The univariate correlations between changes in WBV, SSV, CSV and IBV were all statistically significant, with the exception of that between changes in CSV and IBV; r values ranged from 0.34 (for the WBV/IBV correlation) to 0.80 (for the WBV/SSV correlation). The mean intra-observer coefficient of variations were 1.9% for WBV, 1.5% for SSV, 2.9% for CSV and 2.2% for IBV measurements. The measurement of volume on a portion of brain selectively including the regions in which MS pathology is more diffuse is as reliable and sensitive to disease related changes as that on the whole brain, with significant time saving for processing. PMID- 11200691 TI - Clinical screening for ulnar nerve damage in leprosy patients. PMID- 11200692 TI - Lack of alpha-synuclein gene mutations in families with autosomal dominant Parkinson's disease in Russia. PMID- 11200693 TI - Intramedullary cavernous angiomas and cerebrospinal fluid oligoclonal IgG bands. PMID- 11200694 TI - Jaw tremor in mitochondrial disease associated with the A to G 3243 point mutation. PMID- 11200695 TI - Transitional multiple sclerosis (Schilder's disease): a case report. PMID- 11200696 TI - Full recovery after acute hemorrhagic leukoencephalitis (Hurst's disease). PMID- 11200697 TI - The Miller Fisher syndrome: neurophysiological and MRI evidence of both peripheral and central origin in one case. PMID- 11200698 TI - Pierre Marie (1853-1940). PMID- 11200699 TI - Role of feature space in object-based visual attention. PMID- 11200701 TI - What has changed with riluzole? AB - Riluzole, after two significant trials, was introduced as the first standard treatment of amyotrophic lateral clerosis (ALS) in the early 95'. After 5 years what has changed in the field of ALS? In the field of basic science, riluzole as an active drug has largely contributed to stimulate the research of the possible role of glutamate in the genesis of ALS. However, the apparent simplicity of the relation between the drug and its mechanisms has to modulated in the light of the negativity of other trials (gabapentin) and the display of other mechanisms of the disease and of the compound. Possible relation with other putative mechanisms of ALS, as oxydative stress or growth factors, could be (and probably are) also involved. In the field of its activity, riluzole has an impact on the survival rate which has been largely debated. Comparison with historical databases are supporting the results of the two initial trials. Other information have been published supporting the probable activity of the drug on the muscle strength decline, a controversial matter. They strengthen the initial data and give additional reasons to use riluzole as a standard treatment of patients. In the field of the daily care, riluzole provided a real and unique hope for ALS sufferers. Even if its activity is not as complete as patients would have expected, it provides a hope for slowing down the rate of evolution and abolishes the myth of "no hope, no cure" which was the leitmotiv of patients care until recently. We have to better define the mode of administration with regard to the clinical status of the patients (respiratory disorders, fatigue, stiffness). In the field of care givers, riluzole was one major factor which provided the basis for national and international collaborations either for therapeutic trials or for standard of care. It made possible large collaborative programs in and among many countries. We do hope that this impulse will continue and be stimulated by additional results both in the field of basic science and clinical research. PMID- 11200702 TI - Genetics of amyotrophic lateral sclerosis. AB - The genetic cause of amyotrophic lateral sclerosis (ALS) is known in a minority of cases. Mutations in SOD1, the gene encoding a superoxide dismutase on chromosome 21, are indeed found in 20% of familial ALS patients, who constitute only 5 or 10% of all ALS patients. In rare cases, a mutation in NFH, the gene encoding the heavy subunit of neurofilament, is present. Familial ALS has been linked to other loci but the genes involved remain to be identified. A genetic component is also thought to at least contribute to the pathogenesis of sporadic ALS. Their identification is now possible thanks to progress in molecular genetics. PMID- 11200700 TI - Treatment of amyotrophic lateral sclerosis--what is the next step? AB - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease which was thought to be untreatable. However, recent evidence in both experimental animals and men indicates that antiglutamatergic strategies are the first to have an influence on its pathogenesis and slow down the disease process. Since the effect of drugs is still small, this progress cannot only be seen as a success of the present but must also be acknowledged as a basis for future developments. How will future studies be designed? They will have to take into account that the disease presumably has a long preclinical period and they will use a number of novel compounds and treatment strategies which have been shown to be effective in transgenic animal models. This also implies that we are likely to use a combination of therapies and we will try to treat patients early. The latter will be associated with the demand for a novel clinical attitude toward the diagnosis of the disease and the development of novel markers for both the preclinical period and the longitudinal course of the disease. PMID- 11200703 TI - Guidelines in motor neurone disease (MND)/amyotrophic lateral sclerosis (ALS)- from diagnosis to patient care. AB - This paper reviews the scope of current guidelines in motor neurone disease (MND)/amyotrophic lateral sclerosis (ALS) and examines issues which have arisen in the preparation of these documents. The review concludes with an evaluation of the impact of the guidelines which have been produced to date and looks towards potential future developments in this area. PMID- 11200705 TI - [In Process Citation] PMID- 11200704 TI - [In Process Citation] PMID- 11200706 TI - Current developments and future directions of occupational health in Malaysia. PMID- 11200707 TI - Retrospective review of serologic rubella activity in University Hospital Kuala Lumpur. AB - A retrospective review of rubella serological results carried out in the Virus Diagnostic Unit, University Hospital Kuala Lumpur (UHKL) from January 1993 to September 1999 showed the presence of rubella infection annually which appeared to increase periodically every two to three years. There was no statistical significant difference in the rubella positive rate between male and female population aged 14 to 48 years. Congenital rubella infections (CRI) occurred in babies delivered in UHKL yearly from 1993 to 1998 with an average incidence rate of 48 per 100,000 deliveries. Peaks of rubella cases appeared to be followed by an increase in incidence of CRI cases 6 to 9 months later. The study showed that only 50.8% clinically diagnosed rubella was confirmed by laboratory finding. This study also showed an increase of rubella activity for the months of July, August and September 1999 and this may herald an increase of CRI cases in the coming millennium. PMID- 11200708 TI - Intravenous followed by oral ofloxacin in the treatment of community acquired lower respiratory tract infections in adults requiring hospitalisation. AB - Forty patients were treated with ofloxacin for community acquired lower respiratory tract infections. Eighteen pathogens were isolated in sputum; Streptococcus pneumoniae (4) and Haemophilus influenzae (4) were the most common, followed by Klebsiella pneumoniae (3), Klebsiella spp. (2), Staphylococcus anreus (2), Pseudomonas spp. (2), and Pseudomonas aeruginosa (1). Ofloxacin 200 mg every 12 hours was administered for an average of 3.7 days intravenously followed by 5.4 days orally. Response to therapy was judged to be cure in 38 (95%; 95% C.I., 85%-95%) patients, failure in one (2.5%) and "indeterminate" in one (2.5%). PMID- 11200709 TI - Breast cancer in pregnancy--our experience with six patients in the University Hospital, Kuala Lumpur. AB - Presentation of breast cancer during pregnancy is a rare situation and one that requires a multidisciplinary approach involving an obstetrician, surgeon and oncologist. Management should be along the same principles as in non-pregnant patients and delay is not justifiable. Mastectomy and axillary clearance is the best option, followed by chemotherapy, which is safe after the first trimester. Radiation if required should be delayed until after delivery of the baby. We present here our experience with 6 patients who presented with breast cancer during pregnancy. Five patients refused any treatment until after delivery, while one underwent only a mastectomy and axillary clearance. The outcome was poor; all of them died between 14 months and 52 months. The poor outcome probably reflects the late stage at presentation in four of the patients (State 3 and 4) rather than the delay in treatment, while delay in treatment in the two who presented with early cancer (Stage 1 and 2) led to a more advanced stage after delivery. PMID- 11200710 TI - The efficacy of side arm traction in the reduction of supracondylar fracture humerus in children. AB - 156 consecutive children with supracondylar fracture humerus were reviewed. Of these, 56 children with severely displaced fractures were treated with side arm traction. A retrospective review revealed that a mean post-reduction Baumann angle of 74.2 degrees for boys and 75.9 degrees for girls; and mean post reduction humero-ulna angle of 11.6 degrees for boys and 12.7 degrees for girls was achieved. A linear correlation was noted between the duration of traction and the age of the patient, older patients requiring longer traction. The region below the line in the graph, plotting the duration of traction (y-axis) versus the age of the patient (x-axis) shows when the fracture is unstable; and the region above the line shows when the fracture is stable and can only be reduced by surgery. 10 children presented late; 6 presented within the unstable period and were successfully reduced with traction; while 4 presented stable and required open reduction. We conclude that traction is an acceptable and safe method for reduction of this fracture, and can be used to reduce late presentations while their fractures are still unstable. PMID- 11200711 TI - Autoimmune markers in young Malaysian patients with type 1 diabetes mellitus. AB - This study determined the prevalence and significance of autoantibodies to GAD65 (GAD Ab), insulin (IAA), tyrosine-like phosphatase (IA2) and islet-cell (ICA) in a group of 213 young Malaysian Type 1 diabetics, diagnosed before the age of 40 years. Venous blood was taken at fasting, and at 6 minutes post-glucagon (1 mg i.v.). IAA was detected in 47.4%, GAD Ab in 33.8%, IA2 in 8.9% and ICA in 1.4% of the subjects. When based on post-glucagon C-peptide level of 600 pmol/L, 172 (80.7%) patients had inadequate pancreatic reserve, while the remainder 41(19.3%) showed normal response. The autoantibodies, either alone or in combination, were detectable in both groups of patients; higher prevalence in those with poor or no beta-cell function (73.3% versus 46.3%, p = 0.0001). Although the prevalence of GAD Ab was highest in newly diagnosed patients (< 5 years), unlike IA2 and ICA, the marker remained detectable in 24-25% of those patients with long-standing disease. Nineteen patients could probably belong to the "latent autoimmune diabetes in adults (LADA)" subset, where pancreatic reserve was adequate but patients had detectable autoantibodies and insulin-requiring. On the other hand, 68 of the 213 patients (32%) were seronegative, but presented with near or total beta-cell destruction. Thus, as has also been suggested by others, there is indeed etiological differences between the Asian and the Caucasian Type 1 diabetics, and, there is also the possibility that other, but unknown autoantigens are involved in causing the pancreatic damage. PMID- 11200712 TI - Asthma education: how much does it improve knowledge of childhood asthma amongst medical students and paramedics? AB - The objective of this study was to measure the knowledge of childhood asthma among medical students and paramedics. A previously validated questionnaire about childhood asthma was completed by 281 of 314, third and fifth year medical students at Universiti Kebangsaan Malaysia, Kuala Lumpur. Their knowledge of asthma was assessed during the first and last weeks of their paediatric rotation. A similar questionnaire was completed by 23 of 60 paramedics from various medical disciplines in Hospital Kuala Lumpur. They had attended a two-day seminar on respiratory diseases and their knowledge was assessed prior to and six weeks after the seminar. On the initial assessment the mean score for the final year medical students was 24.5, third year medical students 20.9 and paramedics 18.3. After intervention their mean scores increased significantly to 26.3 (p < 0.0001), 24.6 (p < 0.0001) and 21.3 (p < 0.0001). After intervention, the final year medical students improved significantly in all questions except in the management of acute asthma. Post intervention, third year medical students showed a significant increase in knowledge pertaining to symptomatology, pathophysiology, trigger factors and prophylactic drugs used in asthma management. Although the knowledge of paramedics improved post intervention, they had major deficiencies in knowledge about pathophysiology, trigger factors, preventive and acute asthma therapy, side effects of asthma treatment as well as clinical scenarios. Improvement after intervention was only seen in six of the 31 questions. This study demonstrated an increase in knowledge about childhood asthma among medical students and paramedics after a short intervention. PMID- 11200713 TI - An audit of inpatient case records and suggestions for improvements. AB - A study was carried out in Kuala Lumpur Hospital to review the adequacy of documentation of bio-data and clinical data including clinical examination, progress review, discharge process and doctor's identification in ten of our clinical departments. Twenty criteria were assessed in a retrospective manner to scrutinize the contents of medical notes and subsequently two prospective evaluations were conducted to see improvement in case notes documentation. Deficiencies were revealed in all the criteria selected. However there was a statistically significant improvement in the eleven clinical data criteria in the subsequent two evaluations. Illegibility of case note entries and an excessive usage of abbreviations were noted during this audit. All clinical departments and hospitals should carry out detailed studies into the contents of their medical notes. PMID- 11200714 TI - A comparative study on the service profiles and practice facilities among urban general practices in east and west Malaysia. AB - 1171 urban general practices in East and West Malaysia were compared regarding their service profiles and practice facilities. In general, practices in both parts put important emphasis on preventive health care. More practices in East Malaysia were providing hormone replacement therapy and sexually transmitted diseases services but less were providing intrapartum care, counselling services including sexual and marital counselling and problems associated with social deviance such as alcohol and drug abuse. Although most practices in East Malaysia were solo practices, they were more comprehensive in terms of the provision of practice facilities when compared to those in West Malaysia. A greater number of them had ultrasound facilities, peak flow meters, ECG machines, computers and blood biochemistry facilities. PMID- 11200715 TI - Chinese mothers intention to breastfeed, actual achievement and early postnatal experience. AB - Thirty Chinese primiparous mothers were asked during the antenatal period their breastfeeding intention and then interviewed at delivery and 6 weeks post delivery. One mother had no intention to breastfeed. Ten mothers intended exclusive breastfeeding for one month and 19 for 6 weeks or more. At 6 weeks post delivery only 4 mothers were still breastfeeding. A total of 22 (73%) did not achieve their initial intention. For any future pregnancy, 5 chose exclusive breastfeeding, 22 complementary and 3 formula feeding. Chinese primiparous mothers have high breastfeeding intentions but the majority do not achieve them and their experience has discouraged them from exclusive breastfeeding in future pregnancies. PMID- 11200716 TI - Effect of hemoglobin E on glycosylated hemoglobin determinations using different commercial kits. AB - The effect of HbE, a hemoglobin variant, on the determination of HbA1/HbA1c using 4 commercial kits based on cation-exchange resin, cation-exchange column chromatography and specific antibody techniques was studied. Fifty-eight normal and 63 HbE heterozygous subjects were tested for HbA1 and HbA1c using 4 commercial kits i.e. Eagles Diagnostics, Boehringer Mannehim (BM), Diastat and Ames DCA 2000. Analyses of the samples by the 4 kits were done within one week and samples were stored at 4 degrees C before analysis. The results showed that HbE affects the determination of glycosylated hemoglobin using cation-exchange based and not kits based on specific antibody techniques. PMID- 11200717 TI - Conventional versus endoscopic inferior turbinate reduction: technique and results. AB - Different modalities of turbinate reduction procedures are available for treatment of vasomotor rhinitis not responding to appropriate medical therapy. Amongst these, conventional inferior turbinectomy (non-endoscopic) is the most widely performed procedure. With the advent of nasal endoscopes, inferior turbinoplasty has been gaining popularity worldwide. The purpose of this study was to compare the post-operative complaints and hospital stay of conventional versus endoscopic inferior turbinate reduction techniques performed non-randomly on 15 and 21 patients of vasomotor rhinitis respectively from January 1998 to December 1999 at Hospital Universiti Kebangsaan Malaysia (HUKM). A total of 36 patients (22 males and 14 females) with a mean age of 30.6 years underwent turbinate reduction procedures during this period with a post-operative follow up ranging from 3 months to 6.7 months (mean 3.8 months). There was a significant difference between the conventional and the endoscopic technique with regards to nasal discomfort (p = 0.05) and dry throat (p = 0.02) which was less severe when performed endoscopically. The average hospital stay in hours by the endoscopic technique was almost half compared to the conventional technique. Due to the improved visualisation and minimal post-operative complaints and reduced hospital stay, the technique of endoscopic inferior turbinoplasty is currently the procedure of choice at our center. In septoplasty when endoscopic instrument is not needed, the standard turbinate reduction procedure is still performed. The availability of pre and post-operative acoustic rhinomanometric evaluation will be helpful as an objective measurement of nasal symptoms in the near future. PMID- 11200718 TI - The experience with fine needle aspiration cytology in the management of palpable breast lumps in the University Hospital Kuala Lumpur. AB - A total of 676 palpable breast lumps seen in the Breast Clinic, University Hospital, Kuala Lumpur from August 1993 to August 1994 were subjected to fine needle aspiration cytology. Fifty-four were reported as inadequate, 501 benign, 95 malignant and 26 suspicious. One hundred and eighty-seven aspirates had histological correlation, while 34 of the malignant aspirates had clinical correlation. The majority of the other 455 patients were followed up for a period of 60 to 72 months without any malignancies becoming apparent. For analysis, only the 221 cases with histological or clinical correlation were included, (the suspicious category was included into the positive group and the inadequate cases were excluded), giving a sensitivity of 91.7%, a specificity of 91.7% and a diagnostic accuracy of 91.7%. Breast cytology was an accurate and rapid method of diagnosis of breast diseases, and in a busy surgical unit with limited operating time, it allowed for the triage of patients with breast complaints in deciding which cases needed early open biopsy. A negative cytology does not exclude the possibility of cancer, as there was a false negative rate of 11%. However by utilising a diagnostic triad of clinical examination, radiological assessment and fine needle aspiration cytology, the risk of missing a malignancy is small. PMID- 11200719 TI - Delayed repair of rupture of the biceps femoris tendon--a case report. AB - A rare case of an isolated rupture of the biceps femoris tendon at its insertion to the femoral head is presented. Delayed surgical repair has not been previously reported. In this patient, a successful repair was carried out four months after the injury. PMID- 11200720 TI - Upper genital schistosomiasis mimicking an ovarian tumour. AB - Schistosomiasis is a widely prevalent disease in the world and usually involves the gastro-intestinal and urinary tract. The involvement of the female genital tract has been well-established in S. haematobium infections and is rare with S. japonicum infections. This case involves a Filipino female who was admitted to the University Hospital Kuala Lumpur for right iliac fossa pain and was diagnosed initially as acute appendicitis. Ultrasound showed a multi-septated pelvic cyst leading to a provisional diagnosis of ovarian torsion. Intraoperatively a right parovarian cyst was detected and removed. Histology revealed a congested cyst wall with areas of haemorrhage with several viable and calcified eggs of S. japonicum measuring 85 microns x 62 microns. Within the cystic cavity blood admixed with eggs were seen. Confirmation was carried out by using the indirect haemagglutination (IHA) test. This is a first report of upper genital schistosomiasis mimicking an ovarian tumour. PMID- 11200721 TI - Dysphagia due to anterior cervical osteophytes--a case report. AB - Dysphagia due to osteophytes in a young person is uncommon. We present a rare case of Forestier's disease causing dysphagia in a young lady without other bony involvement. The osteophytes were surgically removed and her symptoms resolved completely. PMID- 11200722 TI - Two cases of severe non-specific oesophageal dysmotility showing different response to botulinum injection therapy. AB - We report 2 cases where treatment of achalasia type symptoms due to severe non specific oesophageal dysmotility have shown symptom resolution and manometric improvement to intrasphincteric botulinum injections either by itself or in combination with oesophageal dilatation. PMID- 11200723 TI - Contralateral pleural effusion during chemotherapy for tuberculous pleural effusion. AB - A 25 year old woman developed a right pleural effusion 6 weeks after commencement of short course chemotherapy for left sided tuberculous pleural effusion. Since the patient improved following continuation of the same treatment, it is presumed to be a case of paradoxical response to anti-tuberculosis treatment. PMID- 11200725 TI - Neisseria meningitidis serotype W135. PMID- 11200724 TI - Localised nodular pulmonary amyloidosis in a patient with sicca syndrome. AB - A 52 year old Chinese woman with a 25 year history of sicca syndrome (primary Sjogrens syndrome) was investigated for 3 episodes of haemoptysis. Clinical examination was unremarkable except for the presence of dry eyes and xerostomia. Computed tomography of the chest revealed a lobulated mass in the posterior basal segment of the left lower lobe. Histopathological examination of this resected nodule confirmed the diagnosis of nodular amyloidosis. The normal radiolabelled serum amyloid P component scintigraphy and the absence of monoclonal plasma cell dyscrasia in the bone marrow strongly support the diagnosis of localised nodular pulmonary AL amyloidosis in this patient. Nodular pulmonary amyloidosis can be associated with sicca syndrome and often simulates bronchogenic carcinoma, bronchiectasis or pulmonary tuberculosis. PMID- 11200726 TI - "Non-infectious" syndromes associated with infectious agents. AB - Over the past two decades there has been numerous new associations between chronic diseases traditionally considered non-infectious with infectious agents. This list of diseases include peptic ulcer, coronary heart disease, neuropsychiatric disorders, haematological disorders and malignancies. These associations have been made possible through improvements in diagnostic tests based on molecular biology techniques. The discovery of these associations is important as it opens up exciting opportunities for the prevention and treatment of many diseases hitherto considered incurable. PMID- 11200727 TI - Stroke in Canada: the need for a new approach. PMID- 11200728 TI - Anemia and iron status in Inuit infants from northern Quebec. AB - The iron status and diet of Inuit infants living in northern Quebec who were part of a prospective cohort study was described. The prevalence of anemia (hemoglobin values > 2 SD below the reference mean) was 21.1% (23/109), 47.4% (55/116) and 37.7% (46/122) at 2, 6 and 12 months, respectively. The corresponding prevalence of microcytic anemia was 0.0%, 4.3% and 21.3%. At 2, 6 and 12 months, iron deficiency anemia (serum ferritin < 10 micrograms/L coupled with anemia) was present in 1.3% (1/79), 24.4% (21/86) and 26.3% (25/95) of infants, respectively. Compared with breastfeeding, the odds ratio for iron deficiency (serum ferritin < 10 micrograms/L) for bottle-feeding with cows' milk or low iron formula was 3.02 (95% CI 1.25-7.27) at 6 months and 3.05 (95% CI 1.28-7.28) at 12 months. This study shows iron-deficiency anemia to be a problem in Inuit infants as young as 6 months old. Breastfed infants were better protected against iron deficiency than infants fed cow's milk or low-iron formula. PMID- 11200729 TI - A systematic review of the relationship between breastfeeding and early childhood caries. AB - This systematic review investigated the relationship between early childhood caries (ECC) and breastfeeding. The systematic review methodology used by the Cochrane Collaboration was modified and adopted for this review. 28 of 151 articles (18.5%) were relevant for the study and were rated as strong (0), moderate (3), weak (9) or very weak (16). Validity scores indicated whether a study met the reviewer's criteria for research rigour. The percentage of studies that received a passing score for each criterion examined were: study design (3.6%), confounders (21%), data collection method (54%), definition of ECC (57%), dental health practices (28%) and infant feeding practices (4%). A lack of methodological consistency related to the study of the association of breastfeeding and ECC, and inconsistent definitions of ECC and breastfeeding, make it difficult to draw conclusions. Moderate articles indicate that breastfeeding for over one year and at night beyond eruption of teeth may be associated with ECC. Due to conflicting findings in less rigorous research studies, no definitive time at which an infant should be weaned was determined, and parents should begin an early and consistent mouth care regime. PMID- 11200730 TI - Child care arrangement and preschool development. AB - Baseline data from the Canadian National Longitudinal Survey of Children and Youth were used to evaluate the associations between child care arrangement and poor developmental attainment (PDA). A weighted total of 521,800 children aged 2 to 3 years were studied (N = 2,709). PDA was assessed by age-standardized motor and social development score. Children were grouped by the predominant type of arrangement: care by someone in the child's own home, in another home (family child care), at a child care centre, or none (child care exclusive to parents). Controlling for socioeconomic status, biological factors and maternal immigration, family dysfunction, hostile parenting and low neighbourhood safety were correlated with PDA and positive parent-child interaction decreased the odds of PDA. Whereas centre child care arrangements were beneficial to development overall (OR = 0.41, 99% CI = 0.18, 0.93), an interaction existed between type of child care and maternal depression; among children with depressed mothers, centre child care was associated with increased odds of PDA. Findings suggest that the associations between child care arrangement and child development involve interactions of factors that influence a child's home environment. Future child development studies exploring these interactions are warranted. PMID- 11200731 TI - Patterns of health care use of injured and non-injured children. PMID- 11200732 TI - Health diaries for monitoring events following immunization. PMID- 11200733 TI - Young adults and HIV vaccine: determinants of the intention of getting immunized. AB - The aim of this study was to evaluate the acceptability of a hypothetical HIV vaccine and to identify the psychosocial determinants of the intention of receiving HIV immunization, based upon Ajzen's Theory of Planned Behaviour (TPB). Of the 136 young adults surveyed, 120 (88%) had a moderate to high intention to receive the HIV vaccine. A logistic regression was performed and two psychosocial factors from the TPB were significant predictors of the young adults' intention of getting HIV immunization: their attitude towards getting HIV immunization (OR = 4.80, CI 95% = 2.08; 13.05) and the perceived behavioural control of getting HIV immunization (OR = 2.52, CI 95% = 1.17; 6.05). These results show that HIV immunization is well accepted by young adults. This finding is particularly relevant because the effectiveness of HIV immunization programs will depend on an individual's acceptance of this vaccine. Also, our results suggest that psychosocial determinants can influence a young adult's decision to receive the HIV vaccine once it becomes available. PMID- 11200734 TI - A profile of cardiovascular disease in northern Ontario: public health planning implications. AB - Cardiovascular disease (CVD) is a leading cause of death in Northern Ontario and therefore considered an important issue. To this end, this paper examines CVD trends in Northern Ontario and the prevalence of known risk factors that give an insight into these trends. Ontario Health Survey 1990, Ontario Health Survey 1996, Canadian Institute for Health Information (1990-95) and Vital Statistics (1990-95) were examined. It was determined that CVD rates in Northern Ontario significantly exceeded those of the province. Further, high prevalence of modifiable risk factors, such as smoking, fat intake, physical inactivity and obesity are all experienced in Northern Ontario when compared to the province. Planning implications, as they relate to collaboration, delivery of services, determinants of health, multiple risk factors and monitoring and evaluation are also discussed. PMID- 11200735 TI - The prevalence and correlates of influenza vaccination among a home care population. AB - OBJECTIVE: To estimate the prevalence and correlates of influenza vaccination in a Home Care population. METHODS: This was a cross-sectional investigation involving linkage of three population-based databases from a rural Alberta Regional Health Authority, i.e., the Regional immunization and the Regional home oxygen information systems to the Regional home care information system. The sample comprised 649 persons who had been admitted or discharged from the Regional Home Care Program in the period Oct. 1-Dec. 31, 1998. An anonymous data file was released to the investigators. We estimated the proportion ever vaccinated against influenza, the proportion vaccinated in the period Oct. 1-Dec. 31, 1998 ("currently vaccinated"); and explored sociodemographic and program correlates of current vaccination. RESULTS: 67% had ever been vaccinated against influenza; 60.7% were currently vaccinated. Factors associated with current vaccination (multivariate analysis) include older age, being married, not receiving nursing services, district of residence and program status. CONCLUSIONS: Influenza vaccination rates were suboptimal. The correlates of vaccination suggest systems-level impediments to influenza vaccination. PMID- 11200736 TI - Health care needs of community-dwelling older adults. AB - OBJECTIVE: To identify, assess, and rank the importance of health care needs of community-dwelling older adults. METHOD: A structured telephone interview with 107 respondents (physicians, direct service providers and administrators) about the importance of a list of 31 health care needs of older adults. Respondents also identified the single most important health issue facing local older adults now and in the next 5 to 10 years. RESULTS: The five most important health care needs, in descending order, are: care-giver support services, community long-term care services, services for people with dementia/Alzheimer's disease, palliative/end-of-life care, and services for cancer patients and their families. Community long-term care services were identified as the single most important health issue both now and in the next 5 to 10 years. CONCLUSION: The study findings should be of value to health and social service researchers, planners, providers and administrators regarding the needs of community-dwelling older adults. PMID- 11200737 TI - Concurrent consultations with physicians and providers of alternative care: results from a population-based study. AB - OBJECTIVE: We examined the factors related to consultations with both physicians and alternative practitioners, compared with visits to physicians only. METHODS: A telephone survey (random-digit dialling) collected information from 818 adults living in and around Saskatoon. Respondents reported consultations with alternative practitioners and physicians in the previous 12 months. RESULTS: Approximately one in five respondents had consulted both a physician and an alternative practitioner. Among respondents under 65 years of age, having one or more chronic medical conditions significantly increased the likelihood of concurrent use of care. Men, individuals suffering from back pain or migraines, those reporting an elevation level of distress, and those for whom spiritual values were important were also more likely to use both types of care. INTERPRETATION: Consultations with alternative care providers occur as an adjunct to, rather than a replacement of visits to physicians. Particular types of medical conditions as well as psychosocial and spiritual factors are determinants of concurrent use of physicians and alternative practitioners. PMID- 11200738 TI - Job stress and burnout among Canadian managers and nurses: an empirical examination. AB - This study examined the relationship of job stress with burnout and its three dimensions (emotional exhaustion, lack of accomplishment and depersonalization), job satisfaction, organizational commitment and psychosomatic health problems. Data were collected by means of a structured questionnaire from Canadian managers (N = 67) and nurses (N = 173). Pearson correlation and moderated multiple regression were used to analyze the data. Job stress was significantly correlated with overall burnout and its three dimensions and job satisfaction in both samples. In the nursing sample, job stress was also significantly correlated with psychosomatic health problems and organizational commitment. Moderated multiple regression only marginally supported the role of gender as a moderator of stress burnout relationship. PMID- 11200739 TI - Should public health workers be able to address the public's health? PMID- 11200740 TI - The Saskatchewan Health and Back Pain Survey: the prevalence and factors associated with depressive symptomatology in Saskatchewan adults. AB - OBJECTIVES: To determine the one-week period prevalence of depressive symptomatology among Saskatchewan adults and to identify sociodemographic and health factors associated with depressive symptomatology. METHODS: The Saskatchewan Health and Back Pain Survey was mailed to an age-stratified random sample of adults. Of the 2,184 eligible subjects, 55% (n = 1131) responded to the survey. We report age-standardized prevalence estimates stratified by age, gender and spinal pain severity. Logistic regression was used to measure the presence and strength of association between various factors and depressive symptomatology. RESULTS: 22.2% (95% CI 19.6-24.9) of adults experienced depressive symptomatology during the previous week, with higher rates in younger adults, in females, and in those with disabling spinal pain. Depressive symptomatology was associated with age, income, smoking, health status, gastro intestinal problems, headaches and spinal pain. CONCLUSIONS: Depressive symptomatology is common in the Saskatchewan adult population, and is related to age, pain severity and general health. PMID- 11200741 TI - Measuring population health: correlates of the Health Utilities Index among English and French Canadians. AB - This study used cross-sectional data from the 1994/95 National Population Health Survey (NPHS) in Canada. The objective of the study was to examine the relationship between several established correlates of health status in the general population and the Health Utilities Index (HUI), a multi-dimensional, preference-based measure of health status. Analyses were carried out separately for the English-speaking (n = 9,853) and French-speaking (n = 1,519) respondents. The index correlated strongly with self-ratings of health status and functional disability and varied as expected according to age, sex, and income. Subjects classified to different categories of chronic conditions reported different levels of health, as predicted. The HUI was also associated with the use of drugs and recent history of hospitalization. No major differences in the findings were observed between the two cultural groups. The results should be treated with caution due to the cross-sectional design and other methodological limitations of the study. PMID- 11200742 TI - Eye exposure to optical radiation in the glassblowing industry: an investigation in southern Ontario. AB - OBJECTIVE: To investigate if the levels of optical radiation hazards in glassblowing are well classified according to the hazard types defined in the Canadian Standards Association (CSA) standard for industrial eye protectors. METHODS: We carried out radiometric measurements, and questionnaire survey in 4 university glassblowing laboratories, and 3 private studios. RESULTS: There is exposure to low levels of UV and IR radiation in all glassblowing operations. A supra-threshold IR radiation level exists in the craft glassblowing. The use of eye protectors is based on past experience regardless of the level of ocular exposure. CONCLUSIONS: Optical radiation hazards exist in both craft and scientific glassblowing. There seems to be an inadequate understanding about radiation types encountered by glassblowers. PMID- 11200743 TI - [How to correctly assess results of pulmonary function tests?]. PMID- 11200744 TI - [Comparison of ventilatory efficiency in alcohol and opiate abusers]. AB - The aim of this study was to evaluate the respiratory efficiency in alcohol and opiate abusers. There were 220 persons under examination: 144 alcohol abusers (group I), 36 opiate abusers (group II) and 40 healthy persons (control group). Both groups of dependent persons were treated in the Detoxication Unit of the Department of Clinical Toxicology CMUJ. During hospitalization the functional state of respiratory system was monitored. Ventilation efficiency was determined on the basis of the results from a "flow-volume" loop, spirometry and the measurements of the respiratory tract resistance in a computerised system Lungtest-MES company (Poland). In the examination performed directly after admission to the Clinic the normal respiratory efficiency was noted in 36.1% in ethanol abusers and 54.9% in opiate abusers. 63.9% of alcohol abusers (group I) and 45.1% of opiate abusers (group II) suffered from the bronchial obturation. In the examination performed after hospitalisation and 9 days of total abstinence in 33.3% of the alcohol dependent patients and in 38.5% of the opiate dependent patients respiratory obturation was observed. The values of respiratory tract resistance in both groups of dependent patients in examination on admission and after treatment were increased compared to controls. The changes of ventilatory parameters can be explained mainly by withdrawal syndrom revealing that it is connected with initial (9 days lasting) period of controlled and total abstinence. PMID- 11200745 TI - [Comparison of respiratory regulation in alcohol and opiate abusers]. AB - Opioid drugs and alcohol, both central nervous system depressants, may also have a depressive action on the brain stem centre responsible for breathing control. Disorders of breathing regulation are reflected in respiratory efficiency. The aim of this study was to evaluate the regulation of breathing by measuring the respiratory pattern and occlusion pressure of abusers of opiates and alcohol. There were 180 persons under examination: 84 alcohol abusers (group I), 36 opiates abusers (group II) and 40 healthy persons (control group). Both groups of dependent persons were treated in the Detoxication Unit of the Department of Clinical Toxicology CMUJ. Respiratory regulation was evaluated "on line" by means of synchronous measurements of the respiratory pattern (according to Milic-Emili assumptions) and occlusion pressure P 0.1 (according to Whitlaw assumptions). The central respiratory drive (VT/Tin) and the timing component of the breathing cycle (Tin/Ttot) were simillar in both groups of abusers. In comparison to the control group, in the group of opiates abusers, values of VT/Tin were higher during examination performed after treatment, and values of Tin/Ttot were elevated (in group I--only before treatment; in group II--before and after treatment). Examination of respiratory pattern and occlusion pressure is based on recording spontaneous breathing, which this can be performed even in unconscious patients in very early stage of poisoning. PMID- 11200746 TI - [Expression of transforming growth factor beta 1 (TGF beta 1) and angiogenesis in broncho-pulmonary carcinoids]. AB - TGF beta 1 commonly produced by normal and neoplastic human cells, has capacity to regulate new blood vessel formation, to establish and maintain the vessel wall integrity; was found to have some significance in the lung cancer prognosis. Tumour angiogenesis is an important factor for tumour growth and metastasis. The purpose of this study was to find, if the immunoexpression of TGF beta 1 has any significance in determination of the histologic subtypes of carcinoids?; to find, if TGF beta 1 has any role and relation to carcinoids angiogenesis?; and to explore TGF beta 1 expression and angiogenesis with respect to metastatic potential of carcinoids. The study was performed on 48 resected broncho-pulmonary carcinoids: 35 typical (TC) and 13 atypical (AC), classified according to the WHO. Semiquantitative analysis for TGF beta 1 was performed. Sections stained using monoclonal antibody against TGF beta 1 were scored in scale from 0 to 4, according to the percentage of positively stained cells (pc) plus percentage of positively stained stroma (ps). The microvessels stained with CD34 monoclonal antibody, were counted in 0.75 mm2 field (microvessel density--MD), using the computerised image analysis system SAMBA 2005 (the morphometric software). The histologic subtype of carcinoids was related to age of the pts (AC occurred in older pts than TC, p = 0.027), to the tumour size (AC were larger than TC: respectively--3.25 cm and 2.4 cm, p = 0.009). Lymph node metastases were significantly more frequent in AC than in TC (38% vs 13%, p = 0.025). 85% carcinoids showed TGF beta 1 expression with various intensity, mainly in the stroma. There was no significant correlation between TGF beta 1 expression and tumour size, the histologic subtype nor the lymph node metastases. The angiogenesis expressed as MD, was not related to histology, nor to the presence of lymph node metastases. There was no correlation between TGF beta 1 expression and angiogenesis. Shown in our study, lack of relation between TGF beta 1 expression and angiogenesis, could support some of the published data indicating indirect action of TGF beta 1 on the angiogenesis. The rich vascularity found in carcinoids morphology could result from TGF beta 1, commonly expressed by the tumoural stroma. The angiogenesis nor TGF beta 1 expression do not determinate the carcinoids histology. PMID- 11200747 TI - [Prognostic value of P53 protein in cells of non-small cell lung cancer]. AB - The aim of the study was to evaluate the prognostic relevance of p53 protein in non-small cell lung cancer. The 95 surgically treated patients were included (53 patients with squamous cell carcinoma, 29--with adenocarcinoma, 5--with large cell carcinoma, and 8--with mixed type). The protein was assessed immunohistochemically with the use of monoclonal antibodies DO7, DAKO. Positive staining was present in 44 patients. There was no survival difference between groups with and without protein (median survival--36 and 33 months, respectively; p = 0.86). In the multivariate analysis the only characteristics with prognostic impact in the entire group was stage of the disease. There was no correlation between the expression of p53 protein and disease-free survival. These results indicate that there is no prognostic relevance of p53 protein in non-small cell lung cancer. PMID- 11200748 TI - [Cytokines TNF-alpha and GM-CSF in BAL from two different segments of lungs defined by high resolution computerized tomography (HRCT) in patients with sarcoidosis]. AB - The aim of the study was to evaluate the concentrations of TNF-alpha and GM-CSF in double BAL (2 x 120 ml) from two different lung segments: (s.A) from upper lobe with the most and (s.B) from lower lobe with the least extensive involvement estimated by high resolution computed tomography (HRCT). Examined group consisted of 28 non-smoking sarcoid patients with homogenous, regular distribution of nodular opacities in conventional chest X-ray (14 F, 14M aged 19-54). In examined patients 16 had nonhomogenous distribution (ND) and 12 had regular distribution (RD) of HRCT changes. Eleven healthy volunteers served as controls. In patients with sarcoidosis we observed the significantly higher concentrations (p < 0.01) of TNF-alpha (3.18 pg/ml, 2.64 pg/ml) and GM-CSF (1.01 pg/ml, 0.95 pg/ml) respectively in BAL fluid from s.A and s.B in comparison with BAL from s.Abis and s.Bbis in control group (TNF-alpha: 0.46 pg/ml, 0.47 pg/ml and GM-CSF: 0.28 pg/ml, 0.31 pg/ml respectively). Mean concentration of TNF-alpha in BAL from s.A (3.77 pg/ml) in ND group was significantly higher than in BAL from s.B in RD group (2.91 pg/ml). TNF-alpha in BAL from s.A in active sarcoidosis was higher than in BAL from s.A and s.B in non-active sarcoidosis. Concentrations of TNF alpha in BAL from both s.A and s.B correlated positively with CD4/CD8 ratio, percentage of lymphocytes, lymphocytes HLA-DR+ and absolute number of CD4 cells and negatively with CD8 cells estimated in BAL from these lung segments. In patients with indications to therapy the level of GM-CSF in BAL from s.A (1.44 pg/ml) was significantly higher (p < 0.05) than in BAL from s.A (0.64 pg/ml) in patients without indications to treatment. We conclude that TNF-alpha and GM-CSF may be involved in sarcoidosis pathogenesis and TNF-alpha may be useful in estimation of sarcoidosis activity. PMID- 11200749 TI - [Usefulness of Dermatophagoides pteronyssinus allergen extract from the Allergopharma J.G. Company for bronchial provocation in patients with bronchial asthma]. AB - The value of Dpt allergen extract, produced by Allergopharma J.G., for performance of the bronchial provocation test in asthmatics was evaluated. The studies were carried out in 40 asthmatics with positive skin prick test with Dpt. Bronchial provocation test was performed according to Ryan's method. After an allergen inhalation, an early asthmatic reaction (EAR) and late asthmatic reaction (LAR) may appear. The following results were observed: a dual asthmatic reaction (EAR and LAR)--in 19 persons, the EAR--only in 9 patients, and the LAR- only in 1 patient. The negative result of the provocation were found in 11 patients. The frequency of particular patterns of the bronchial reactions was similar to those published before by us and other authors, with different allergen extracts. The allergen extract of Dpt from Allergopharma J.G. can be used to bronchial challenge. PMID- 11200750 TI - [Value of the immunochromatographic assay for detecting IgG antibodies against 38 kDa mycobacterial antigen in diagnosis of tuberculosis]. AB - Despite of a fast development in the techniques of rapid identification of mycobacteria by molecular genetic techniques, serodiagnosis may be of special values as non-expensive, easy to perform method. Several serodiagnostic tests, principally those using immunoenzymatic (ELISA) methodology are available. The goal of our study was to evaluate one step coloured immunochromatographic assay detecting IgG antibodies against antigen 38 kDa (Rapid Test TB). Our material consisted of 278 serum samples--tuberculosis (n = 155), healthy (n = 36), sarcoidosis (n = 50), lung cancer (n = 25) mycobacterial infections other than tuberculosis (n = 12). Tuberculosis group consisted of new culture positive cases (n = 66), new culture negative cases (n = 23), chronic cases (n = 43) and extrapulmonary TB (n = 23). Specificity of 96% and sensitivity of 54% was obtained. In pulmonary TB sensitivity of 50% and in extrapulmonary TB of 74% was obtained. In chronic cases sensitivity of 70% and in new cases of 40% was received. Sensitivity of 44% in new culture positive cases and 30% in new culture negative cases was obtained. We conclude that immunochromatographic test may be a very useful tool improving tuberculosis diagnosis, especially in extrapulmonary tuberculosis. Strip test may be an interesting alternative as it is an extremely simple, rapid, and cheap technique. PMID- 11200751 TI - [Guidelines for diagnosis and treatment of mucoviscidosis. Consensus of the Polish Mucoviscidosis Working Group]. PMID- 11200752 TI - [A rare mediastinal neoplasm in the form of a hemangioma]. AB - Hemangiomas of the mediastinum are rare tumors. They represent fewer than 0.5% of the mediastinal tumors. Because of their rarity, the diagnosis and treatment of these tumors is difficult. We present a case of venous hemangioma of the mediastinum in a young woman. Despite of routine examination applied in mediastinal tumors the appropriate diagnosis was not done by the accessible methods. PMID- 11200753 TI - [The role of human papilloma viruses (HPV) in the pathogenesis of lung neoplasms]. PMID- 11200754 TI - [The role of gamma interferon in host immune response to tuberculosis]. PMID- 11200755 TI - [Serologic methods in diagnosis of tuberculosis]. PMID- 11200756 TI - [Hellp syndrome. Toward a definition of the length of conservative treatment] . PMID- 11200757 TI - [Maternal and perinatal morbidity and mortality associated with hellp syndrome] . AB - OBJECTIVES: Our purpose was to describe the effects of serious obstetric complications on maternal and perinatal outcome in pregnancies complicated by Hellp syndrome. STUDY DESIGN: Retrospective study. PATIENTS: Sixteen patients managed from January 1994 through December 1998 in whom pregnancy was complicated by Hellp Syndrome. RESULTS: The incidence of Hellp syndrome among women with severe preeclampsia and/or eclampsia (164 cases) was 9.7%. Fourteen cases occurred before and two after delivery. In nine cases, Hellp occurred before 32 weeks of gestation and later in two other cases. Mean gestational age at delivery was 32.4 weeks. Serious maternal morbidity included acute renal failure (five cases), disseminated intravascular coagulation (two cases), pulmonary oedema (one case), severe ascites (five cases), pleural effusion (three cases), adult respiratory distress syndrome (one case). Abruptio placenta, acute renal failure and disseminated intravascular coagulation were always associated. Ten patients required transfusions with blood products. Caesarean delivery was performed in 15 cases. General anaesthesia was used in all patients. There was one maternal death from multiple organ failure. Perinatal outcome was poor. Six perinatal deaths were related to abruptio placenta, intrauterine asphyxia and extreme prematurity. CONCLUSION: The high maternal and perinatal mortality and morbidity reported with the presence of Hellp syndrome requires maternal-fetal follow-up in a tertiary centre where intensive maternal and neonatal care are available. PMID- 11200758 TI - [Complications of difficult tracheal intubations in a critical care unit] . AB - OBJECTIVES: This study was performed in order to evaluate the frequency of DI, the predictive factors of DI and to list the related complications. STUDY DESIGN: Prospective non randomized, open study. PATIENTS AND METHODS: All patients intubated in the critical care unit during the five months of the study were included. The previous history and clinical setting of the patients, the conditions and the complications of intubation were collected. DI was defined when the procedure required more than two laryngoscopies. RESULTS: The study included 80 patients. The rate of DI was 22.5%. The Mallampati score (p < 0.001) was the only predictive factor. The frequency of complications was 25%. This rate was 55% for DI versus 16% for easy intubations (p < 0.001). CONCLUSION: This study confirms the high incidence of DI and associated complications in critical care. We suggest the development of airway management protocols in critical care unit in order to reduce the rate of DI. PMID- 11200759 TI - [Periodic evaluation of practices in postoperative pain management] . AB - OBJECTIVE: Periodical assessment of practices as part of a quality assurance program: impact on postoperative pain. PATIENTS: All patients evaluated from the first postoperative day during a week. METHODS: Two surveys performed at a six month interval after establishment of some corrective measures. Different items were evaluated: pre-anaesthesia information for patients, pain severity and satisfaction with pain treatment. Medical data were consulted concerning postoperative analgesic prescriptions, their realization, pain assessment by nurses. Between the two surveys, first survey results were presented to anaesthesiologists. Then guidelines for prescriptions were suggested and new monitoring guidelines were proposed to nurses in surgical ward. RESULTS: 94 patients were evaluated during each survey. Patients had undergone orthopaedic, visceral, urology, ophthalmology and vascular surgery. Half of the patients did not receive information about pain before surgery. 43% of patients had a pain scores = 30/100 during movements; no difference was found between the two evaluations. Satisfaction graded as "moderate or insufficient" decreased from 22% (1rst survey) to 10 (2nd survey) (p < 0.05). Non steroidal anti-inflammatory drugs and nefopam prescriptions increased between the two surveys (p < 0.05). Association of three or four analgesics increased between the two surveys and monotherapies decreased (p < 0.05). Concordance of prescriptions with guidelines was 55% during first survey and 62% during the second (NS). Pain severity was not recorded for 36% of patients at first survey and in 18% at the second (p < 0.05). CONCLUSION: Although anaesthesiologists and nurses changed their practice due to a quality insurance program concerning postoperative pain, its consequence on the severity of postoperative pain was not significant. PMID- 11200760 TI - [Sensitivity to atracurium in the lateral abdominal muscles] . AB - OBJECTIVE: To study the effect of atracurium on the electromyographic activity of the lateral abdominal muscles and adductor pollicis in anaesthetized subjects. STUDY DESIGN: Prospective, comparative, open study. PATIENTS AND METHODS: Sixteen patients, ASA physical status 1 or 2, undergoing elective orthopaedic surgery under general anaesthesia were studied. Anaesthesia was induced with propofol/fentanyl and orotracheal intubation performed after glottic local anaesthesia without using muscle relaxant. Anaesthesia was maintained with isoflurane/nitrous oxide/oxygen and fentanyl reinjections. Supramaximal percutaneous stimulations in a simple twitch mode (0.1 Hz) were applied at the 9th-10th intercostal nerve on the posterior axillary line and at the ulnar nerve at the wrist. The electromyographic responses were registered using skin surface electrodes, placed on the D9-D10 dermatome in regard of the lateral abdominal muscles and of the thenar muscles. After a single bolus dose of atracurium 0.5 mg.kg-1, the following parameters were studied: the maximum effect (Emax), the time for obtaining Emax (Delay) and the recovery time of 5, 10, 25, 50, 75 and 100% of the control neuromuscular response (T5, T10, T25, T50, T75, T100). RESULTS: The dose of 0.5 mg.kg-1 of atracurium induced 100% block in both lateral abdominal muscles and adductor pollicis. Lateral abdominal muscles blockade had faster onset (136 +/- 4 s versus 205 +/- 29 s) and shorter recovery, T5, T10, T25, T50, T75 and T100 were significantly (p < 0.05) shorter than at the adductor pollicis. CONCLUSION: Lateral abdominal muscles blockade have faster onset and recovery than adductor pollicis. PMID- 11200761 TI - [Perioperative autotransfusion with salvage blood in cancer surgery] . AB - OBJECTIVES: Intraoperative blood cells salvage using a Cell Saver technique is controversial in oncologic surgery because tumor cells could be aspirated and reinfused to the patient. The goal of this review was to discuss the risk associated with this technique, and the way to minimize it. DATA SOURCES: A review of the literature has been made by questioning PubMed site (http://nbci.nlm.nih.gov) on the period of 1968 to 2000. The key words were: intraoperative blood salvage, blood transfusion, autologous, cancer. Cases reports have been excluded. STUDY SELECTION: Tumor cells aspirated and reinfused have been numbered in both experimental and clinical studies. In clinical studies, the outcome after intraoperative cells salvage/reinfusion has been compared to published data or historical groups of allogeneic transfusion, all in non randomized studies. DATA SYNTHESIS: Both experimental and clinical studies confirmed the presence of cancer cells in the blood either aspirated or reinfused. However, six clinical studies with limited number of patients did not show metastatic spread associated with Cell Saver. The addition of leukocyte filters reduces greatly this quantity of cancer cells. Irradiation of the pack did not destroy tumor cells but blocked their proliferative capacity. In the other hand, some infiltrative tumors were shown to have permanent cancer cells seeding, quantitatively superior to the seeding observed when a Cell Saver is used. CONCLUSION: It seems reasonable to use the Cell Saver in oncologic surgery, if possible with a leukocyte filter, not only in case of unexpected major bleeding (consensus), but also in programmed cases with high risk of huge hemorrhage. PMID- 11200763 TI - [Colon hernia through a defect in the iliac crest after bone graft harvesting] . AB - A case of a patient with an hernia through a defect in the iliac crest after bone graft harvesting is described. The osseous defect provides a rigid ring against which repeated sudden elevations in abdominal pressure can result in disruption of soft tissue and herniation of abdominal contents. Standard plain radiographs and barium studies are of limited interest and may even be misleading in diagnosing the herniation. Findings on computed tomography led to detection of this abnormality, and should be the first line exam in these cases. PMID- 11200762 TI - [Unusual course of a pulmonary artery catheter through a persistent superior vena cava] . AB - We report the unusual course of a pulmonary artery catheter through a persistent left-sided superior vena cava. After left subclavian vein cannulation and downward left-sided paramediastinum course, the Swan-Ganz catheter enters the right pulmonary artery. Haemodynamic monitoring was consistent with the diagnosis of septic shock developed by this 56-year-old woman, after cephalic duodenopancreatectomy. Persistent left-sided superior vena cava occurs in 0.5% of the population and 5-10% of patients with congenital heart diseases. It drains into the right atrium through the coronary sinus in 92% of cases and is associated with an absent right superior vena cava in 20% of cases. The left sided superior vena cava persists when the caudal part of the left anterior cardinal vein does not degenerate. A persistent left superior vena cava may be medically relevant during implantation of pacemaker leads or radiofrequency ablation, during cardiac surgery for placement of a retrograde coronary sinus cardioplegia catheter and during transjugular intrahepatic portosystemic shunt placement. PMID- 11200764 TI - [Treatment with danaparoid during pregnancy for a woman with a cutenous allergy to low-molecular-weight heparin] . AB - The authors describe a case of heparin-induced skin reaction due to two preparations of low molecular weight heparin in a pregnant woman. The main characteristics of heparin-related cutaneous allergy are reported. The use of an heparinoid, usually indicated for patients with heparin-induced thrombocytopenia, appeared to be efficient and safe for the mother and her fetus. An epidural analgesia was performed for labor analgesia, 24 hours after the last injection of danaparid of sodium. PMID- 11200765 TI - [Anaphylactic reactions to aprotinin: intradermal diagnostic tests] . AB - A 66-year-old patient, undergoing heart surgery, developed an anaphylactic reaction following the first administration of a test-dose of aprotinin. Skin tests were performed six months later. Prick-tests with 10(-2) and 10(-1) aprotinin dilutions were negative but intradermal reaction with a 10(-3) dilution was clearly positive. The level of aprotinin specific IgE was high, both in the serum obtained before surgery and in the one sampled on the day of the testing. As no reaction was observed during the tests, skin-testing and specific IgE appear to be an interesting alternative to a potentially dangerous test-dose, but they both need further evaluation. PMID- 11200767 TI - [Bronchial intubation and celioscopy: attention!] . PMID- 11200766 TI - [Case report of acute intoxication from intravenous injection of petroleum] . AB - A 18-year-old patient injected intravenously 2.5 mL of paraffin oil into the right upper limb. It caused a local thrombophlebitis with a slow evolution. A collapsus occurred on the sixth day. The authors obtained a clinical recovery of the limb after heparine and oral anticoagulation. PMID- 11200768 TI - [A fatal rhabdomyolosis from an unusual etiology: Clarkson syndrome] . PMID- 11200770 TI - [Antibiotic prophylaxis for surgery] . PMID- 11200769 TI - [Gas or liquid peridural puncture] . PMID- 11200771 TI - [Continuing medical education and evaluation] . PMID- 11200772 TI - [Cost-benefit relations of different strategies for control of nausea and vomiting] . PMID- 11200773 TI - Progression of premalignant MCF10AT generates heterogeneous malignant variants with characteristic histologic types and immunohistochemical markers. AB - The MCF10AT premalignant human breast epithelial cells form benign ductal structures in immunodeficient mice which sporadically progress to carcinoma in situ and invasive cancers of different histologic types. MCF10CA1 cell lines are malignant variants derived by serially passing small pieces of tumors in athymic mice before establishing cells in culture. As these MCF10CA1 variants gave rise to heterogeneous tumors, some cell lines were cloned. Inoculated into immunodeficient mice, these variants produce squamous carcinomas with an undifferentiated component or adenocarcinomas also with an undifferentiated component. Immunohistochemistry utilized antibodies against DF3, c-erbB-2, cyclin Dl, m keratin, p keratin, p53, B72.3 and estrogen receptor. We detected characteristic patterns for squamous carcinomas, for adenocarcinomas, and for each undifferentiated component, that is the undifferentiated components of the squamous and glandular carcinomas were distinct. Only adenocarcinomas were focally ER positive. One uncloned variant that produced cancers with a glandular component, MCF10CA1h, was cloned and cells were injected into mice. This clone produced only undifferentiated carcinomas that, compared to tumors formed by the parental uncloned variant, had lost ER, DF3 and c-erbB-2 expression, but more strongly expressed p53. Our data demonstrate the potential of the premalignant MCF10AT model to generate heterogeneity, including both estrogen receptor positive as well as estrogen receptor-negative tumors, during progression. PMID- 11200774 TI - Loss of heterozygosity in bilateral breast cancer. AB - Women who develop bilateral breast cancer at an early age are likely to harbour germline mutations in breast cancer susceptibility genes. The aim of this study was to test for concordant genetic changes in left and right breast cancer of young women (age < 50) with bilateral breast cancer that may suggest an inherited breast cancer predisposition. Microsatellite markers were used to test for loss of heterozygosity (LOH) in left and right tumours for 31 women with premenopausal bilateral breast cancer. Markers adjacent to or within candidate genes on 17p (p53), 17q (BRCA1), 13q (BRCA2), 11q (Ataxia Telangiectasia-ATM) and 3p (FHIT) were chosen. Mutational testing for BRCA1 and BRCA2 was performed for cases where blood was available. Concordant LOH in both left and right tumours was demonstrated for at least one of the markers tested in 16/31(54%) cases. Where allelic loss was demonstrated for both left and right breast cancer, the same allele was lost on each occasion. This may suggest a common mutational event. Four cases showed concordant loss of alleles in both left and right breast cancer at D17S791 (BRCA1). BRCA1 mutations were identified in two of these cases where blood was available. Four cases showed concordant LOH at D13S155 (BRCA2). Concordant LOH was further demonstrated in seven cases for D11S1778 (ATM) and four cases for D3S1300 (which maps to the FHIT gene), suggesting a possible role for these tumour suppressor genes in this subgroup of breast cancer patients. No concordant allelic loss was demonstrated for D17S786 suggesting that germline mutations in p53 are unlikely in such cases of bilateral breast cancer. PMID- 11200775 TI - Utilization of professional supportive care services by women with breast cancer. AB - This paper reports on the results of a survey of utilization of professional supportive care services by women with breast cancer, and on patterns of differential service utilization by sub-groups of patients. Study participants were women with invasive breast cancer diagnosed 23-36 months prior to contact about the study, and randomly selected from the Ontario Cancer Registry. From among 1,119 eligible women sent survey questionnaires, 731 returned completed questionnaires (65%). A total of 31% of respondents reported accessing one or more of the following professionals: social worker, psychologist, psychiatrist, dietitian, physiotherapist. Among those who responded to a question about whether they would have liked specific services, 34% reported that there was at least one professional supportive care service they would have liked to use, but were unable to access. Factors shown to be related to greater utilization of services included: younger age, higher household income, employed or student status, private health insurance coverage, and having received chemotherapy. Overall, there was a surprisingly low utilization of professional specialized supportive care services among women with breast cancer. Policy implications include finding strategies to better inform cancer patients about existing services, and ensuring that a core set of services are available to all patients. PMID- 11200776 TI - Antimitotic and cytotoxic effects of theophylline in MDA-MB-231 human breast cancer cells. AB - A variety of cancer cell lines, including MDA-MB-231 human breast cancer cells, exhibit mitotic inhibition by cAMP. In earlier work, we found that the phosphodiesterase inhibitor, theophylline, reduced the number of cells and altered cellular morphology. In the current study, we evaluated the effects of theophylline on macromolecule synthesis and indices of cell viability. Theophylline evoked a concentration- and time-dependent decrease in DNA synthesis. However, the net decrease in cell number was greater than that predicted solely from mitotic arrest. Assessment of protein synthesis indicated a second effect of theophylline separable from that on DNA synthesis. This was confirmed by decreased cell viability and adhesion. Exposure of the cells to the phosphodiesterase inhibitor, IBMX, in concentrations that produced inhibition of DNA synthesis equivalent to that seen with theophylline, elicited a smaller reduction in cell number. Theophylline also evoked specific changes in the expression or function of membrane-bound adenylyl cyclase activity, effects that are likely to contribute to sustained reactivity of these cells to other cAMP related inhibitors of cell proliferation, such as isoproterenol. The multiple pharmacologic properties of theophylline, producing mitotic inhibition, cytotoxicity and altered signaling in MDA-MB-231 cells, may provide insight into novel therapeutic strategies. PMID- 11200777 TI - Inflammatory breast carcinoma: pathological or clinical entity? AB - Inflammatory breast carcinoma (IBC) diagnosis is usually based in the presence of typical clinical symptoms (redness and edema in more than 2/3 of the breast), which are not always associated with pathologic characteristics (subdermal lymphatics involvement). Whether exclusively pathologic findings without clinical symptoms are sufficient for IBC diagnosis remains controversial. A retrospective analysis of 163 clinically diagnosed IBC (CIC) either with dermal lymphatics invasion or not, was compared with another group of 99 patients with dermal lymphatics invasion without clinical symptoms (occult inflammatory carcinoma) (OIC). The following clinical and pathological characteristics have been analyzed and compared: age, menopausal status, clinical axillar node involvement, symptoms duration before diagnosis, grade, estrogen receptors, presence of metastases at diagnosis, local recurrence, metastasic dissemination, disease-free (DFS) and overall survival (OS). Median age was younger in CIC (52.3 vs. 63.8 years; p < 0.001). Symptom duration before diagnosis were significantly shorter in CIC (3.4 vs. 6.8 months: p < 0.0001). Visceral (36.2% vs. 17.2%; p = 0.001) and brain metastases (7.4% vs. 1%; p = 0.02) was significantly more frequent in CIC. Negative estrogen receptors were more frequent in CIC (34.9% vs. 65.1%: p < 0.004). Five-years DFS (25.6 vs. 51.6%; p < 0.0001) and OS (28.6 vs. 40%; p < 0.05) were shorter in CIC. CIC (regardless of subdermal lymphatics involvement) must be clearly differentiated from OIC. Prognosis of CIC patients is poorer, so this two entities should be clearly differentiated when therepeutic results are reported. PMID- 11200778 TI - Long-term morbidity following axillary dissection in breast cancer patients- clinical assessment, significance for life quality and the impact of demographic, oncologic and therapeutic factors. AB - OBJECTIVE: This study describes in detail the surgery-related symptoms following axillary lymph node dissection in breast cancer patients and considers both their significance for long term quality of life and the impact of possible influencing factors. MATERIAL AND METHODS: Three hundred and ninety six patients were studied retrospectively using a self-report questionnaire and a clinical examination. The symptoms, numbness, pain, edema, arm strength and mobility were evaluated. The subjective assessment of the degree of symptom intensity was compared with objective measurements. The extent of surgery (number of resected nodes, level of dissection) as well as the influence of demographic, oncologic and adjuvant measures (age, time interval, number of involved nodes, chemotherapy) were evaluated. RESULTS: Shoulder-arm morbidity and fear of cancer recurrence were the most important long-term sources of distress following breast cancer surgery in our study population. Demographic, oncologic and therapeutic measures including the extent of surgery had no influence on long-term morbidity. The intensity of all evaluated symptoms was reported to be more severe in patients' subjective statements than in the results of clinical assessment. CONCLUSION: Shoulder-arm morbidity following axillary dissection is a frustrating polysymptomatic disease that seems to be relatively unaffected by therapeutic measures. The surgical trauma necessary for adequate tumor staging (removal of 10 lymph nodes) seems decisive for the postsurgery syndrome following axillary dissection. For node positive patients complete axillary clearing may improve tumor control without worsening long-termmorbidity. New techniques, such as the sentinel-node-biopsy, that selects patients with negative axillary status while preserving the integrity of axillary structures, may improve the overall morbidity. PMID- 11200779 TI - Effect of melatonin and linolenic acid on mammary cancer in transgenic mice with c-neu breast cancer oncogene. AB - Breast cancer is one of the most common cancers and is a leading cause of mortality in women. The TG.NK transgenic mouse line expresses the c-neu breast cancer oncogene under the control of a MMTV promoter and appears to be a useful animal model for evaluation of intervention strategies to delay/prevent breast cancer. Fiber-rich nonpurified diet (NTP-2000) and some retinoid analogues have been shown to significantly delay the development of mammary cancer in the TG.NK model. Four-week-old hemizygous TG.NK female mice with MMTV/c-neu oncogene fed NTP-2000 diet were gavaged with 0.05-0.2 ml of flaxseed oil as the source of omega-3 rich PUFA, or melatonin at 50-200 mg/kg or a combination of 0.10 ml flaxseed oil and 50 mg/kg melatonin in a gavage volume of 0.2 ml per mouse with corn oil as the vehicle for 30 weeks. The time course of the mammary tumor incidence pattern was advanced by flaxseed oil compared to the control. At the high dose (0.2 ml) of flaxseed oil, when the omega-6: omega-3 PUFA ratio was closer to 1, there was some delay in the growth of mammary tumors. Melatonin delayed the appearance of palpable tumors and the growth of the tumors with a dose-related statistically significant negative trend for the incidence of tumors. The combination of flaxseed oil and melatonin caused a significant decrease in the number of tumors and tumor weight per mouse compared to the control and to flaxseed oil but not to melatonin alone. Flaxseed oil may delay the growth of mammary tumors if the omega-6:omega-3 PUFA ratio of fat consumed is closer to 1. Melatonin has the potential to markedly delay the appearance of palpable mammary tumors. Studies are in progress with the TG.NK mouse model to understand the histological and molecular changes associated with the dose response pattern of mammary tumor incidence and growth after treatment with a broad range of doses of melatonin. PMID- 11200780 TI - Clinical characteristics of adolescent headache. AB - We evaluate clinical characteristics of headache in a group of subjects > 12 years to assess the sensitivity and specificity of the IHS criteria. We consider whether age at onset may influence the clinical features. We used a semi structured questionnaire to examine 136 patients consecutively referred to our division. We considered the following subdiagnoses: IHS 1.1, 1.2, 1.7, 2.1, 2.2, 2.3. Migrainous disorders were found to be more common than non-migrainous headaches. A definite diagnosis was established in 68.1% of the migrainous group and in 86.6% of the tension-type headache group. Unilateral location, severe intensity of pain, the presence of nausea, vomiting, phonophobia and photophobia were features which differed between migrainous and non-migrainous subjects. No difference was found regarding aggravation of the headache by physical activity. On the basis of the criterion duration of attacks < 2 hours, IHS 1.7 was found to differ significantly from other migraine types. With the exception of the presence of vomiting in migrainous patients, the age at onset was not found to be a factor influencing the characteristics of the headache. Diagnostic criteria for migraine were highly specific but poorly sensitive, and those for tension-type headaches highly sensitive but less specific. The sensitivity/specificity of the IHS criteria in adolescent migraine can be influenced by the heterogeneity of the clinical characteristics. In fact, the intensity, the location and the quality of pain were similar to those found in childhood migraine, while the concomitant symptoms were less frequent than in childhood and in adult migraine. Further studies are needed to define the degree of severity of the clinical features in adolescent headache and to address the question of the validity of the IHS criteria. PMID- 11200782 TI - "From 0 to 18": what happens to the child and his headache? AB - Prospective and retrospective studies showed that headaches (migraine and tension type) with childhood or adolescent onset have age-related characteristics and change over time, with high rate of type changing, remission or improvement. The reasons are unknown. On the other hand, several studies focused on factors that may be precursors of childhood headaches. All these factors may allow a developmental arc to be outlined, defining the natural history of headache from birth to adulthood. Familial (genetic?) influence, hyperreactivity, periodic syndromes and anxiety in childhood are factors that may predict headache onset, against the background of developmental modulation of pain. Biological and psychological factors are probably reciprocally involved, although the link is unclear. The identification of prognostic factors could allow a better framing of headaches and, from an integrated perspective, have important implications as regards clarifying the "nature" of headache. PMID- 11200781 TI - Headache in teenagers: comorbidity and prognosis. AB - A representative, prospective population sample of 1,205 7-year-old children in a larger Finnish city was followed for 15 years for headache and other medical disorders and symptoms. The comorbidity associated with headache was found to be higher than expected. Allergy and bronchial asthma, diabetes mellitus and stomachache were more common in boys than in girls, while psychiatric symptoms and sleep disturbances were more typical of girls than boys. The prevalence rate of any headache and migraine increases up to the age of 13 years, but after that age, a decline in the prevalence is found in boys, while girls show an increasing trend both in the presence and in the frequency of any headache and migraine. PMID- 11200783 TI - Headache in adolescents in Dutch general practice. AB - We set out to describe the occurrence of headache in adolescents in general practice, the diagnoses made, the referrals to specialised care and the role of psychosocial problems in idiopathic headache. Data from the Dutch national survey of morbidity and interventions in general practice were used. The practice population (103 practices) comprised 37,187 children aged 12-18 years. In 650 episodes headache was a reason for encounter. The incidence of headache as presented to the GP was 69.9 per 1000 person years. The incidence in girls was twice as high as in boys. Half of the episodes with headache complaints were related to an infectious disease. The incidence rate of idiopathic headache was 18.0 per 1000 person years. Eight percent of all headache episodes were diagnosed as a psychosocial problem. Of all episodes, 25% percent were diagnosed as idiopathic headache (i.e. headache as symptom diagnosis, tension headache or migraine). Of these episodes, 21% were associated with an underlying psychosocial problem. Referrals were made by the GP in three percent of all headache episodes and four percent of idiopathic headache episodes. Headache in adolescents is a common reason for visiting a general practice. The symptom is often associated with an infectious disease. The GP is aware of underlying psychosocial problems. Only few children are referred for specialist care. PMID- 11200784 TI - Hypothalamic resetting at puberty and the sexual dimorphism of migraine. AB - It is well known that migraine is far more represented in females than in males. However, this gender-related difference is present only during reproductive life since in prepubertal children, migraine prevalence figures are independent of sex. Thus, transition to puberty accounts for changes which render females more susceptible to migraine attacks. In females, the main driver of the hormonal events allowing sexual maturation is the pulsatile secretion of hypothalamic LHRH modulated by opioid activity. Clinical reports suggest that migraine attacks could be prevented by the abolition of this neurohormonal secretion. On the other hand, several clinical and experimental observations have focused on neuroendocrine systems (opiatergic, serotonergic, adrenergic) as participating in the constitution of the so-called "migraine trait", the biological predisposition in patients that would explain their sensitivity to migraine triggers. Such neuroendocrine secretions are mainly dependent upon hypothalamic activity where a sexual dimorphic nucleus has been discovered in the preoptic area. We suggest that the sexual dimorphism of migraine should be sought in hypothalamic networks related to LHRH secretion. PMID- 11200785 TI - Migraine associated with menstruation. AB - Many women report increased frequency of migraine in association with menstruation. The term 'menstrual' migraine is often used despite lack of an agreed definition. The International Headache Society has classified most headaches but not 'menstrual' migraine. A proposed definition is based on the finding that the prevalence of migraine increases on day 1 +/- 2 of the menstrual cycle. Attacks occurring at this time of the cycle are typically without aura. Effective acute therapy is the mainstay of management for menstrual and non menstrual attacks although there is some evidence that attacks linked to menstruation are less responsive to treatment compared with migraine at other times of the cycle. If several attacks occur throughout the cycle, standard prophylactic agents should be used. Women with exclusive 'menstrual' migraine may benefit from perimenstrual prophylaxis but this should only be instigated once the association between migraine and menstruation has been confirmed with prospective records kept for a minimum of three cycles. NSAIDs are the treatment of choice in reducing migraine associated with menorrhagia and/or dysmenorrhoea, otherwise perimenstrual oestrogen supplements using percutaneous or transdermal oestrogens are recommended. Combined oral contraceptives are useful for women requiring contraception although there is a tendency for attacks to occur during the pill-free interval. If these are contraindicated, depot progestogen is an alternative as it also inhibits ovulation and can improve migraine, provided amenorrhoea is achieved. Oral progestogen-only contraception has little place in the management of 'menstrual' migraine as it does not inhibit ovulation and is often associated with a disrupted menstrual cycle. Some women consulting with menstrual migraine are menopausal and may be considering hormone replacement therapy. Studies suggest that non-oral routes of delivery of oestrogen, which provide stable levels, are more likely to improve migraine than oral oestrogens, which produce variable day-to-day levels. Too low a dose of oestrogen is ineffective at controlling symptoms but too high a dose, particularly if coupled with surges of endogenous oestrogen, can trigger migraine aura. Once the route and dose has been optimised, continuous oestrogens can control migraine as well as menopausal symptoms. Additional progestogen, necessary for unhysterectomised women, can exacerbate migraine. To minimise this, progesterone derivatives or non oral routes of delivery are recommended, with continuous regimens used where possible. PMID- 11200786 TI - Central and peripheral mechanisms of migraine. AB - Central (cortex and upper brainstem) and peripheral (trigeminovascular) mechanisms are involved in the pathophysiology of migraine. We propose that unknown migraine triggers initiate depolarization of cortical neurons followed concomitantly by a transient increase in blood flow. This transient hyperemia spreads at a rate of 3-6 mm/min followed by hypoperfusion which is more long lasting. Through unknown mechanisms (probably chemical), we hypothesize that this wave activates or sensitizes trigeminovascular axons which is a consequence of neuropeptide release and neurogenic inflammation. Orthodromic conduction along trigeminovascular fibers transmits information centrally via the trigeminal caudalis and other brainstem nuclei to higher cortical structures for registration and modulation of nociceptive information. PMID- 11200787 TI - Dopaminergic hypersensitivity in migraine: clinical and genetic evidence. AB - Migraine is a common disorder characterized by recurrent pain attacks of mild severe intensity associated with autonomic and occasionally neurological symptoms. The migraine attack is a complex process that involves both central and peripheral structures. Various pathogenetic hypotheses have been proposed but the pathophysiology of the disease is still unknown. The study of the pathophysiology of migraine includes the investigation of neurotransmitter systems and their potential role in the development of the attack. Several studies performed since the '60s have demonstrated the key role of serotonin. The theory whereby hypersensitivity of the dopaminergic system may be involved in the pathogenesis of migraine has been supported by various authors on the basis of clinical, pharmacological and recent genic evidence. Recent neurophysiological studies performed using new techniques have led to a correlation of migraine with central nervous system disorders characterized by an altered neuronal excitability. Migraine seems to be characterized by a low threshold of neuronal excitability which is in turn regulated by genetic factors involving the dopaminergic system. A genetically determined hypersensitivity of the dopaminergic system may be involved in the onset of the migraine attack. PMID- 11200788 TI - Dopamine involvement in the migraine attack. AB - Clinical evidence and recent genetic findings seem to indicate an involvement of dopamine in the pathophysiology of the migraine attack. Prodromal symptomatology (mood changes, yawning, drowsiness, food craving), accompanying symptoms (nausea, vomiting, hypotension) and postdromal symptoms (mood changes, drowsiness, tiredness) may be related to dopaminergic activation. The dopaminergic system could also play a role in the headache phase, either by taking part in nociception mechanisms, or by regulating cerebral blood flow. A body of pharmacological findings seems to support this involvement. Migraine patients, between attacks, show a higher responsiveness to acute administration of dopaminergic agents. Apomorphine administration induces in migraineurs more yawns as well other dopaminergic symptoms e.g. nausea, vomiting, dizziness. Migraine has been associated with hypotension and, occasionally, with syncope. Bromocriptine causes severe orthostatic syndrome in migraine patients. Both piribedil and apomorphine markedly increase cerebral blood flow of migraine patients, thus indicating enhanced responsiveness of dopamine receptors which are involved in cerebral blood flow regulation. Interictal dopaminergic hypersensitivity has also been demonstrated by means of neuroendocrine tests. Altered dopaminergic control of prolactin secretion exists in migrainous women. L deprenyl, a MAO-B inhibitor, is significantly more effective in reducing prolactin levels in migraineurs than in controls. Taken together, these findings support the view that hypersensitivity of peripheral and central dopaminergic receptors is a specific migraine trait. Finally, a high density of lymphocytic D5 receptors has been found in migraine sufferers, thus suggesting their upregulation. Therefore, the hypothesis that dopaminergic activation is a primary pathophysiological component in certain subtypes of migraine, namely those characterised by marked dopaminergic symptomatology, has been advanced. From this perspective, a blockade of dopaminergic hyperresponsive receptors can be considered as a rationale for the therapy of migraine. PMID- 11200789 TI - Rational migraine management: optimising treatment with the triptans. AB - In the last two years, a number of 5-HT1B/1D agonist triptans with enhanced lipophilicity (TELs) relative to the first drug of this class, sumatriptan, have been approved for marketing in most countries of the world (naratriptan, rizatriptan and zolmitriptan). In addition, at least three others are in advanced stage of clinical development (almotriptan, eletriptan, and frovatriptan). This paper sets out to review the recent data with the aim of identifying: 1) What are the critical differences between the TELs and sumatriptan? 2) How do the currently licensed TELs compare? 3) Is it possible to provide a rational approach to migraine therapy based on objective differences in the clinical profile of these new drugs? Recent randomised controlled and comparator data were reviewed, including the independent FDA assessment of rizatriptan. Critical differences for the new TELs (naratriptan, rizatriptan and zolmitriptan) which may lead to more rational migraine management: Both rizatriptan (10 mg) and zolmitriptan (2.5 mg and 5.0 mg) have demonstrated superior efficacy to sumatriptan 100 mg, and 25 and 50 mg respectively. Therefore, for first line use either rizatriptan or zolmitriptan would be appropriate for moderate and severe headache. Rizatriptan has a more rapid onset of action than sumatriptan 100 mg. Both rizatriptan and zolmitriptan have a more rapid onset of action than naratriptan. Therefore, for a rapid onset of action either rizatriptan or zolmitriptan would be appropriate. Naratriptan would appear to have a lower recurrent headache rate than sumatriptan, rizatriptan or zolmitriptan. However, 24-hour efficacy rates for zolmitriptan 2.5 mg were significantly greater than for sumatriptan 25 mg and 50 mg and were not significantly different from naratriptan. Therefore, for headaches of long duration and with a tendency to recur (e.g. menstrual headaches) either naratriptan or zolmitriptan would be appropriate. Naratriptan has lower reported adverse event rates comparable with placebo. This would support the use of naratriptan 2.5 mg in patients who have demonstrated poor tolerance to the "triptan type" adverse events. PMID- 11200790 TI - Effect of nitric oxide donors on the central nervous system--nitroglycerin studies in the rat. AB - The demonstration that nitrovasodilators act as nitric oxide (NO) donors has favored a resurgence of interest in this class of compounds. The demonstration of the different biological effects of NO in various districts, including the central nervous system, suggests a possible role for these substances besides their well-known cardiovascular activity. Among the various nitrovasodilators commercially available, nitroglycerin represents a well known substance to headache experts because of its capability to provoke spontaneous-like migraine attacks in headache-free migrainous subjects. Basic research has recently demonstrated that nitroglycerin activates a variegate set of brain nuclei following systemic administration via the intervention of selected neurotransmitters and neuromediators, with a specific time-pattern in different brain areas. Increasing evidence suggests that nitroglycerin-induced neuronal activation is mediated by multiple mechanisms that include direct neuronal and vascular action of nitroglycerin-derived and endogenously-synthesized NO, as well as indirect effects related to nitroglycerin-induced changes in cardiovascular and trigeminovascular systems. The study of the neurovascular effects of nitroglycerin in the rat provides relevant information for a better understanding of the pathophysiology of migraine attacks and of their triggers. PMID- 11200791 TI - New methods for evaluating acute treatments in migraine. AB - The crescendo of activities in the field of migraine therapy, has led to the emergence of a class of molecules, the triptans, that are similar in terms of their activity on serotonin receptors, but which actually differ from one another, as each one has its own peculiar clinical profile. A careful examination of their clinical activity and their validation with objective methods may promote the wise use of each drug, make room for new products, and allow patients to make their own choices. PMID- 11200792 TI - The effectiveness of combined oral lysine acetylsalicylate and metoclopramide (Migpriv) in the treatment of migraine attacks. Comparison with placebo and oral sumatriptan. AB - In two, double-blind, randomised, clinical, trials (RCTs), oral lysine acetylsalicylate (1620 mg, equivalent to 900 mg aspirin) combined with metoclopramide (10 mg) (LAS + MTC) was compared with placebo, and with oral sumatriptan (100 mg) in one of these RCTs. In both RCTs the LAS + MTC combination was superior to placebo with therapeutic gains (percentage relief after active treatment minus percentage relief after placebo) of 30% and 31% for the first treated attack. These therapeutic gains are in the same range as those found for 100 mg oral sumatriptan, and in the comparative RCT the LAS + MTC combination was quite comparable to 100 mg sumatriptan, with success rates for the first attack of 57% and 53%, respectively. PMID- 11200793 TI - NSAIDs: behind the mechanisms of action. AB - Non-steroidal anti-inflammatory drugs (NSAIDs) are a heterogeneous group of compounds. These heterogeneous agents have a similar therapeutic action for the treatment of pain, fever and inflammation. The major mechanism of action of NSAIDs is the inhibition of cyclooxygenase (COX), the enzyme catalysing the synthesis of prostaglandins (PGs). Appropriate and effective treatment for migraine depends upon an accurate diagnosis. The goals of treatment are amelioration of the symptoms of an acute attack and prevention of further attacks. PMID- 11200794 TI - The relevance and application of disease management and pharmacoeconomics to migraine. AB - Disease management is a comprehensive approach to improving the outcomes for patients suffering from chronic disease. It has frequently been applied to diseases like diabetes and asthma but, to date, has not widely been regarded as particularly relevant to migraine. Yet a number of factors suggest that this view might usefully be reconsidered, notably the dissatisfaction with migraine control expressed by many patients and the inconsistencies in treatment patterns observed across clinical practice. Another factor is the growing range of therapeutic options available to manage the disorder. In this latter respect, decision-making must not only be governed by individual patient needs, but also by considerations of clinical cost effectiveness. Pharmacoeconomic analysis can play a useful role in determining the relative value for money offered by different treatments and is increasingly being applied in migraine. It is clear, however, that full realisation of its potential contribution requires progress to be made in a number of key areas, perhaps most importantly agreement on the definition of successful treatment. PMID- 11200795 TI - Headache burdens and bearers. AB - All elements of headache burden, and those who bear them, need to be identified if headache is to secure its rightful place in the priority queue for scarce healthcare resources. This paper sets out to do this. Illness manifesting as headache imposes substantial burdens on individual people and on society. Whilst different diagnostic categories of headache vary quantitatively in their impact, the elements of burden are similar for all common headaches. Migraine, being the most studied, is a good model. The AASH/IHS Consensus Symposium on Improving Migraine Management, held in Washington DC on October 2nd 1998, argued that, world-wide, migraine is both under-diagnosed and under-treated. Whilst improved allocation of healthcare resources to migraine and other headache illnesses will mitigate these burdens, this will not happen unless the size and full nature of the problem are recognised. Using rhetoric, I answer two questions: what are the burdens of headache, and who bears them? Migraine has a peculiar tendency to extend its burdens beyond attacks and to others than the immediate sufferer. In many cases it should be characterised as a chronic rather than episodic illness. Other categories of headache impose qualitatively similar and heavy and widely placed burdens. Healthcare resources expended on better treatment are likely to be repaid several-fold by savings elsewhere. PMID- 11200796 TI - Headache in the Diagnosis-Related Groups (DRG) era: management and appropriateness of admission. AB - Headache is an extremely common disorder which has a marked impact on the utilisation of healthcare resources and constitutes a considerable socio-economic burden. The related costs, both direct and indirect, are especially high in developed countries, since headache predominantly affects an economically-active section of the population. The Diagnosis-Related Groups (DRG) system, a method for reimbursing healthcare structures for patient admissions, was introduced in Italy in 1995. The aim of the system was to control public health expenditure and to promote better distribution of financial resources. Here, we report the results of the application of the DRG system to headache patients admitted to the Department of Neurology of the University of Pavia in 1996 and 1998. The financial analysis revealed high fixed costs (hospital running costs per days of hospitalisation); by contrast, the impact of the variable costs (those relating to the direct management of the individual patient, i.e. examinations, therapeutic interventions etc.) was low. It was found that reducing the number of days of hospitalisation increases the hospital's income and reduces the mean loss incurred in each DRG. It is therefore suggested that a complete approach to the management of headache must include educational programmes for patients and general practitioners, and that access to headache centres and to hospital care should be restricted to cases of acute, severe headache, or recurrent, chronic headache with/without drug abuse or dependence. PMID- 11200797 TI - Quality assurance system using ISO 9000 series standards to improve the effectiveness and efficacy of the Headache Centre. AB - The ISO 9000 series has been adopted as a reference standard and operating system for a Quality Assurance project involving all the units of the Polyclinic of Modena, within which the Headache Centre operates, to guarantee a clearly-defined standard of service to the client and the promotion of continuous quality improvement. The implementation of the quality system, which necessitated analysis and description of the process of headache diagnosis and treatment currently being applied, highlighted those aspects that did not conform with the quality objective, primarily, the long waiting list for admission. Since ready accessibility is a basic requisite for the quality of health care services, a new organisational set-up was introduced, and is still in place, with the aim of enabling patients who are really in need to be admitted to the Headache Centre without undue delay. PMID- 11200798 TI - Peripheral and central sensitization during migraine. AB - Current theories propose that the pain of migraine is caused by chemical activation of meningeal perivascular fibers. In an animal model of migraine, we have recently shown that chemical activation of meningeal primary afferent nociceptors that innervate the dura could lead to the following: a) peripheral sensitization of these nociceptors to intracranial mechanical stimulation; b) central sensitization of second-order trigeminovascular neurons that receive convergent input from the dura and skin to extracranial mechanical and thermal stimulation; and c) facilitated cardiovascular pressor responses that are usually indicative of pain. These findings provide the first set of evidence for the induction of peripheral and central sensitization along trigeminovascular pain pathways by visceral input from the intracranial dura. We propose that the throbbing pain of migraine is mediated mainly through peripheral and to a lesser extent through central sensitization, and that the development of scalp tenderness is mediated mainly through central sensitization. PMID- 11200799 TI - The search for novel migraine therapies: experimental models. AB - The identification and development of the potent 5-HT1B/1D agonist, sumatriptan has resulted in new therapeutic opportunities for the treatment of migraine and a number of chemically novel agents with a similar mechanism of action have been identified. Whilst these agents are optimised to enhance the therapeutic effect of sumatriptan, development of mechanistically novel therapies may provide new directions for the care of migraine sufferers. To develop new treatment paradigms, novel chemical entities should be evaluated in animal models which are predictive of therapeutic efficacy e.g.: in animal models where sumatriptan has shown activity, or the pathophysiological processes involved in the disease must be targeted. Therefore, investigation of mechanisms underlying cortical activity and its involvement in the activation of trigeminal vascular pathways may allow better understanding of the disease and result in the identification of new non triptan-like therapies. PMID- 11200800 TI - Pharmacology of emesis and gastrointestinal motility: implications for migraine. AB - This paper outlines the physiopharmacology of emesis and its gastrointestinal motor correlates in relation to the possible treatment strategies of a migraine attack. The gastrointestinal motor correlates of vomiting consist of a stereotyped motor response to diverse stimuli and basically include gastric relaxation and a series of events (intestinal motor inhibition and disruption of slow wave activity) in preparation for the occurrence of a retrograde giant contraction that propagates orally and empties intestinal contents into the stomach. These motor correlates always accompany vomiting, but may also appear as an independent phenomenon. Antidopaminergic agents, such as metoclopramide and domperidone, have antiemetic/prokinetic properties, block the gastrointestinal motor correlates of vomiting and may speed up absorption of antimigraine agents. The use of 5-HT4 receptor agonists may be an alternative strategy to achieve prokinesia during a migraine attack, although this issue still needs to be fully addressed by controlled studies. Sumatriptan was found to induce gastric relaxation and delay gastric emptying, but the impact of these effects during a migraine attack remains to be determined. PMID- 11200801 TI - A pathophysiological view of primary headaches. AB - The cerebral circulation is innervated by sympathetic, parasympathetic and sensory nerves which store a considerable number of neurotransmitters. The role of these has been evaluated in primary headaches. A clear association between head pain and the release of calcitonin gene-related peptide (CGRP) was demonstrated. In cluster headache and in a case of chronic paroxysmal headache there was in addition release of vasoactive intestinal peptide (VIP) which was associated with facial symptoms (nasal congestion, rhinorrhea). In parallel with sumatriptan treatment head pain subsided and neuropeptide release normalised. These data show the involvement of sensory and parasympathetic mechanisms in the pathophysiology of primary headaches. PMID- 11200802 TI - Central and peripheral mechanisms in migraine: a neurophysiological approach. AB - The author briefly reviews the main evidence in favour of both central and peripheral factors supposed to take part in the complex pathomechanisms leading to the activation of the trigemino-vascular system in the migraine attack. PMID- 11200803 TI - From neurophysiology to genetics: cortical information processing in migraine underlies familial influences--a novel approach. AB - Migraine patients show impaired cortical information processing between attacks with deficient habituation of pattern-reversal visual evoked potentials (VEP), and strong intensity dependence of auditory cortical evoked potentials (IDAP). This could be a genetic trait as certain genetic patterns are known for evoked potentials in healthy subjects. VEP-habituation and IDAP were studied in 40 migraine patients, i.e. pairs of 20 parents and their children. We developed a novel approach based on Monte Carlo statistics to selectively assess vertical familial influences. Both groups, parents and children, were characterized by abnormal VEP-habituation and IDAP. However, similarity between related pairs was far more pronounced than similarity between unrelated pairs. Assessed with a novel statistical approach, familial influences proved to be highly significant in determining cortical information processing in migraineurs, thus supporting the important role of genetic factors. PMID- 11200804 TI - Neurophysiological evidence of increased cortical reactivity in migraine. AB - Cortical reactivity in migraine can be studied with evoked potentials. The majority of the evidence shows increased reactivity in migraine, which may be due to abnormal inhibition. At present, the techniques are not useful for diagnosis. Discrepancies between reports may be due to fluctuations in reactivity over time. Documenting this changing reactivity requires refinement of analysis techniques. PMID- 11200805 TI - Contingent negative variation as indicator of duration of migraine disease. AB - Amplitudes of early wave contingent negative variation (iCNV) reveal significant differences between migraine patients and healthy controls, indicating a lack of habituation and pronounced attentional functions in migraine patients. CNV amplitudes were recorded in 20 migraine patients. The CNV amplitudes were Pearson correlated with the individual duration of the migraine disease. Only iCNV correlates inversely with the duration (r = -.544). The data show an influence of duration of migraine disease on iCNV amplitudes. It is suggested that iCNV is an indicator of chronicity in persistent migraine. PMID- 11200806 TI - Clinical and para-clinical tests in the routine examination of headache patients. AB - Para-clinical examinations in the diagnosis and treatment control of headache patients vary considerably between clinics and headache centers. Among the neurological societies in Europe there has been a consensus that some common procedures and recommendations should be created. In the Fall of 1998, the European Federation of Neurological Societies (EFNS) commissioned a Task Force on Neurophysiological Tests and Imaging Procedures in Headache Patients. Members of the Task Force are the present authors and we have reviewed the literature on 1) neurophysiological tests (EEG and evoked potentials), 2) autonomic nervous system and clinical tests and 3) imaging and cerebrovascular tests (X-ray, CT, MR, fMRI, PET, SPECT and transcranial Doppler). The literature was carefully evaluated with respect to validity and strength of the data. The task was to reach conclusions about each technique in the form of guidelines for clinical use. Finally, selected areas for future research will be outlined. The extensive review and the guidelines will be published by the EFNS during 2000. PMID- 11200807 TI - Clinical management of young patients presenting with headache. AB - Headache is a common symptom in young patients and requires a clearly structured, individual approach. The history and the clinical examination are prerequisites for planning further management of the condition. The IHS classification is particularly useful in the differential diagnosis of idiopathic headache. Additional diagnostic testing should not be performed routinely, but on an individual basis depending on the patient's history and neurological findings. The acute therapy of idiopathic headache in young patients has been evaluated in few studies only. However, there is general agreement that (in subjects requiring medication) paracetamol, acetylsalicylic acid and ibuprofen are most useful for treating migraine attacks, whereas analgesics should widely be avoided in tension type headache. For the prophylaxis of migraine and tension-type headache, non pharmacological measures such as regulation of lifestyle, relaxation training and psychological or psychotherapeutic interventions are much more important than pharmacotherapy, which is required in a small number of patients only. PMID- 11200808 TI - Experimental models of migraine. AB - Experimental models have been developed to study various aspects of migraine. Here we describe the most commonly used models--mostly animal models--which led to the development of a pathophysiological concept of migraine. We focus on activation studies of the trigeminovascular system, the sphenopalatine ganglion, the superior sagittal sinus, the dura mater as well as blood vessels. The most common consequences of activation are noted and include protein extravasation, neuropeptide release, rCBF and diameter changes, c-fos expression and electrical neuronal activity. In addition, we briefly summarize the results of cortical spreading depression studies, as they relate to the human migraine aura. These models will continue to be useful to elucidate migraine pathophysiology and explore drug mechanisms. PMID- 11200809 TI - The early history of the American Society for Reproductive Immunology: a personal memoir. PMID- 11200810 TI - Inhibition of the antibody responses to rat blood transfusion antigens in mice by boar seminal immunosuppressive fraction. AB - PROBLEM: Immunosuppressive fraction of boar seminal vesicle fluid (ISF) was tested to muffle primary and secondary antibody responses to xenotranfusions. Contemporaneously, heparin non-binding fraction of seminal plasma (H- fraction), presumed to be identical to ISF, was used to support the results. METHOD: To study their similarity, ISF and H- fraction were analyzed by high-performance liquid chromatography and the separated proteins by N-terminal sequencing. In sera of mice treated with ISF or H- fraction, the productions of antibodies against rat erythrocytes and blood serum were evaluated by enzyme-linked immunosorbent assay (ELISA). The productions of IgM, IgA, and IgG subclasses were followed by sandwich ELISA. RESULTS: ISF and H- fraction were proved to be equal complexes of porcine seminal plasma (PSP) proteins PSP I and PSP II. Both inhibited antibody responses to rat erythrocytes and serum and the concentrations of IgM, IgG, IgG1 and IgG2 after the first transfusion with a long-lasting effect. Both suppressed the secondary antibody production if applied before the second transfusion. IgA and IgG3 stayed uninfluenced. ISF and H- fraction had an equal immunosuppressive effect. CONCLUSIONS: ISF was characterized biochemically, found to be identical to H- fraction, and determined to be powerful in overcoming unwanted exaggerated antibody responses to xenotransfusion. PMID- 11200811 TI - Intravenous immunoglobulin therapy influences T cell adhesion to extracellular matrix in women with a history of recurrent spontaneous abortions. AB - PROBLEM: To determine activated T cell adhesion level to extracellular matrix (ECM) in non-pregnant women with a history of recurrent spontaneous abortions (RSA). In addition, to evaluate a small-dose intravenous immunoglobulin (IVIG) therapy influences on T cell adhesion to ECM. METHOD OF STUDY: Phytohemaglutinin (PHA) or phorbol myristate acetate (PMA) activated T cell adhesion to the following extracellular matrix proteins: collagen IV, fibronectin and elastin were studied in women with the history of RSA. In addition, IVIG immunotherapy influence on T cell adhesion was studied. Normal T cells adhesion values were established in non-pregnant healthy women with the previous successful pregnancy outcome and in normal healthy pregnant women. RESULTS: PHA activated T cell adhesion to collagen IV (P = 0.04), fibronectin (P = 0.0003) nad elastin (P = 0.02) were significantly higher in women with the history of RSA when compared to non-pregnant healthy women wit the previous successful pregancy outcome. IVIG immunotherapy normalized the T cell adhesion level and favored a successful pregnancy. CONCLUSIONS: Increased T cell adhesion to collagen IV, fibronectin and elastin characterize women with the history of RSA. Decreased T cell adhesion to the main extracellular matrix components of human placenta may underlie possible effect of IVIG action. PMID- 11200812 TI - Theoretical basis for herbal medicines, Tokishakuyaku-san and Sairei-to, in the treatment of autoimmunity-related recurrent abortion by correcting T helper-1/T helper-2 balance. AB - PROBLEM AND METHOD OF STUDY: To get insight into the basis for the empirical usage of herbal medicines in the treatment of recurrent abortion, we examined whether Tokishakuyaku-san (Toki) and Sairei-to (Sai) modulate T helper-1 (Th1) and T helper-2 (Th2) cytokine release from peripheral blood mononuclear cells (PBMCs). The effects of these medicines were investigated as related to human leukocyte antigen (HLA)-G, a non-classical HLA class I antigen expressed on trophoblasts and a putative crucial player involved in fetomaternal immune interplay. RESULTS: Toki and Sai increased the release of Th1 group cytokines, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma while preserving the inhibitory effect of HLA-G on the release of these cytokines. As for Th2 group cytokine release, Toki was without effect in modulating interleukin (IL)-4 release, regardless of the presence of HLA-G, whereas Sai nullified the effect of the presence of HLA-G to stimulate the release of IL-4 without affecting its release in the absence of HLA-G. CONCLUSION: Toki and Sai may have therapeutic potential, particularly in autoimmunity-related recurrent abortion where Th2 response is pathologically enhanced, but not in recurrent abortion involving alloimmune fetomaternal derangement, a condition of, rather, an enhanced Thl response. PMID- 11200813 TI - Enhanced expression of Fas-associated proteins in decidual and trophoblastic tissues in pregnancy-induced hypertension. AB - PROBLEM: To determine if feto-placental tissues from gestations complicated by pregnancy-induced hypertension (PIH) have altered expression of Fas-associated proteins. METHOD OF STUDY: The expression of several Fas-related proteins was determined in fetal membranes, decidua, and placentas obtained from PIH-affected (n = 12, age range 32-36 weeks) and normal (n = 6, age range 37-41 weeks) gestations. Paraffin-embedded tissue sections were stained with specific monoclonal antibodies to Fas, Fas ligand (FasL), caspase-3, and bax. RESULTS: We observed greater expression of Fas and FasL in amnion and decidua from PIH affected gestations than in normal controls. Intense staining was observed only in the perivascular endothelium (caspase-3) and in decidual cells (bax) from PIH gestations. CONCLUSION: Differential expression of Fas-related proteins in fetal membranes, decidua, and placentas from PIH-affected gestations is consistent with increased apoptosis, and suggests activation of the Fas/FasL pathway in a tissue specific manner. PMID- 11200814 TI - Identification of epididymis-specific antigens using neonatal tolerization. AB - PROBLEM: Conventional immunization using whole sperm containing multiple antigens as the immunogen followed by hybridoma technology usually gives antibodies to antigens invariably of testicular origin, probably because of the strong immunogenic nature of these antigens. Therefore, an alternate approach of neonatal tolerization or subtractive immunization has been utilized to raise antibodies specific to epididymis by suppressing immune response to testicular antigens. METHOD OF STUDY: Neonatal mice were tolerized with testicular sperm proteins on days 0 and 5. These animals were then immunized with epididymal sperm proteins on day 21, followed by two boosters at biweekly intervals. Sera from these mice were used to localize epididymis-specific antigens. RESULTS: Sera from mice that were tolerized to testicular sperm proteins and later immunized with epididymal sperm proteins reacted only with epididymal proteins. CONCLUSION: The results of this study demonstrate that neonatal tolerization with testicular sperm proteins, followed by immunization with epididymal sperm proteins, enhances the production of antibodies to proteins exclusively of epididymal origin. PMID- 11200815 TI - Nitric oxide (NO) and interleukin-1beta (IL-1beta) in follicular fluid and their correlation with fertilization and embryo cleavage. AB - PROBLEM: Using an IVF model, the goal of the study was to investigate the relationship between follicular fluid (ff) NO and IL-1beta levels, as well as their correlation with fertilization of mature oocytes and embryo cleavage rates. METHOD OF STUDY: Follicular fluid was collected from 17 patients at the time of transvaginal oocyte retrieval following controlled ovarian stimulation. Oocytes harvested from these follicles were followed through fertilization and embryo cleavage. The NO metabolites nitrate/nitrite (NO3/NO2) were measured using the Griess reaction as an indirect assessment of NO activity. IL-1beta was measured using a high sensitivity ELISA system (Amersham, UK). The Student's t-test was utilized for unpaired data with the means considered significantly different when P < or = 0.05. RESULTS: Follicular fluid NO3/NO2 levels were significantly lower in follicles containing mature oocytes that fertilized (n = 30; 9.7 +/- 1.0 microM), versus those that did not fertilize (n = 23; 15.4 +/- 2.4 microM; P < 0.05). Follicles that contained oocytes that fertilized and went on to divide beyond the 6 cell stage had significantly lower ff levels of NO3/NO2 (n = 18; 7.5 +/- 0.9 microM), as compared to ff that contained oocytes that did not fertilize or failed to develop beyond the 5 cell stage (n = 35; 14.6 +/- 1.7 microM; P < 0.01). No correlation was found between ff NO3/NO2 levels (n = 28; 13.8 +/- 2.0 microM) and ff IL-1beta levels (n = 28; 0.5 +/- 0.08 pg/mL). An analysis of ff IL 1beta levels in relation to fertilization and embryo cleavage rates revealed no correlation. CONCLUSIONS: Lower ff NO3/NO2 levels at the time of oocyte retrieval are associated with adequate fertilization and embryo cleavage rates. In our IVF model, no correlation was found between ff IL-1beta levels and ff NO3/NO2, fertilization, or embryo cleavage rates. PMID- 11200816 TI - Expression of functional chemokine receptors of human placental cells. AB - PROBLEM: Chemokine receptors of placental trophoblasts possibly act as co receptors or alternative receptors of maternal fetal infection by HIV. To clarify their possible expression and the physiological roles of chemokines on human placentae, we studied chemokine chemokine receptor expression and the effects of exogenous chemokines on choriocarcinoma cell lines. MATERIALS AND METHODS: Placental samples were obtained from 13 placentae of various gestational ages. Villous tissue was mechanically dissected from samples. Trophoblasts were enriched by anti-human chorionic gonadotropin (hCG)-coated magnetic beads. Human choriocarcinoma cell lines (JAR, BeWo, JEG-3) were maintained in RPMI 1640 media supplemented with 10% FCS. Expression of chemokine receptors was studied by RT PCR. The effects of MIP-1alpha, RANTES, MCP-1 on hCG production were estimated by EIA. Effects of chemokines on proliferation of choriocarcinoma cell lines were examined by MTT assay. RESULTS: We observed mRNA expression of CCR-1, 2, 3, 4, 5 and CXCR-1, 2, 4 in 1st trimester placental villi, CCR-I, 2, 4 and CXCR-1, 2. 4 in 2nd trimester placental villi, CCR-1, 2, 4 and CXCR-4 in 3rd trimester placental villi. Using MACS enriched trophoblasts, we observed identical results. A choriocarcinoma cell line BeWo expressed CCR-1, 3, 4 and CXCR-1, 2, 4 while JEG 3 and JAR expressed CCR-1, 3, 4, 5 and CXCR-1, 2, 4. Expression of the CCR-5 and CXCR-4 protein in choriocarcinoma cell lines and MACS-enriched trophoblats were confirmed by flow cytometry. Chemokine MCP-3, MIP-1alpha, RANTES mRNA were expressed by the 1st, 2nd and 3rd trimester placental samples and the three choriocarcinoma cell lines examined. MCP-1 was expressed by 1st and 2nd trimester placental villi. Administration of chemokines up-regulated proliferation (10(-1) 10 ng/mL) and hCG production (10(-1) - 10(-2)ng/ mL) of the three choriocarcinoma cell lines examined. CONCLUSIONS: Our results suggest possible roles of chemokines/chemokine receptors on placental physiology and their involvement in HIV transmission as alternative receptors. PMID- 11200818 TI - Quantitative cell and matrix changes in human humeral head osteoarthritic cartilage. AB - A new quantitative method was devised both to establish an objective standard for morphometric diagnosis and to determine the extent of degeneration in osteoarthritic cartilage. Eight normal and forty-eight osteoarthritic humeral heads, subsequently confirmed by light microscopy, were obtained at necropsy. The articular cartilage was observed in situ with a laser scanning confocal microscope (LSCM) and morphometric measurements determined cell density (cells/mm), cell volume fraction (%) and mean cell volume (microm3). The osteoarthritic cartilages were classified according to the following four characteristics: increase in thickness, increase in cell volume fraction, decrease in cell volume fraction, and fibrous pannus. Deviations in cell density and cell volume fraction from normal means were calculated as extent of degeneration. Our present approach aims to provide valuable clues, such as objective stereological information and a unique reference for biochemical and traditional morphological analyses, that clinicians will be able to use in combination with other methods in order to establish a reliable diagnosis. PMID- 11200817 TI - Regulation of IgE-receptor expression, IgE occupancy and secretory capacity of mast cells. AB - Mast cells play an important role in initiating and modulating allergic and inflammatory reactions. Their responsiveness is determined by three important factors: the expression of IgE receptors on the cell surface, the IgE occupancy of these receptors, and the intrinsic secretory capacity of the cells. In this review, we will summarise some findings relevant to these three aspects of mast cell function, and discuss possible regulatory mechanisms. It appears that the genetic background as well as environmental factors influence all three of these components of the response. T cells appear to play an important role in regulating the IgE-receptor expression and also, independently, the intrinsic secretory capacity of mast cells via an unidentified route, possibly involving the secretory signal transduction chain directly. IgE itself appears to have an important role in the regulation of IgE-receptor expression, as indicated by the upregulation of receptors in vitro in the presence of IgE, and the absence of IgE binding capacity of mast cells in IL-4 gene knockout mice, lacking IgE production. The IgE-receptors of mast cells are saturated to a high degree under different normal conditions, without an obvious relation to antigenic stimulation, also in athymic animals. We have suggested that this basal IgE content on mast cells may be the result of an antigen-independent production of IgE directed by the mast cells themselves and serving regulatory purposes, modifying the secretory response and preventing a massive possibly harmful degranulation. PMID- 11200819 TI - Erythema migrans--influence of posture. Case report. AB - Despite widespread awareness of the most classical clinical presentation with central clearing of erythema migrans, a pathognomonic sign of infection with Borrelia burgdorferi, diagnosis of other forms of erythema migrans remains more difficult. We describe a case of a patient with secondary lesions of erythema migrans that within three months formed a complicated pattern and affected at last nearly the entire lower limb of the patient. In addition, the erythema appeared to be posture-dependent in the way that the lesion was with central clearing in the supine and with homogeneous appearance in the upright position. The borrelial infection was confirmed by PCR sequencing that detected DNA of B. afzelii in the skin biopsy specimen. The lesions disappeared during antibiotic therapy. This case shows how posture can be important in the examination of patients with a suspected erythema migrans. PMID- 11200820 TI - Glomerular structure in lithium-induced chronic renal failure in rats. AB - The effects of long-term lithium administration on glomerular structure and intervention with angiotensin converting enzyme inhibitor (ACEI) were studied in rats. Male Wistar rats were fed a lithium-containing diet (Li) or control diet (C) for 16 weeks postnatally. Li-treated rats developed renal failure, hypertension and proteinuria. During the subsequent 24 weeks, subgroups were treated with ACEI. The kidneys were fixed by perfusion, and tissue blocks were serially cut for estimation of glomerular volume and glomerular characteristics by light microscopy. Mesangial and mesangial matrix volume fractions, surface density of capillary walls, basement membrane thickness and foot process width (FPW) were measured by electron microscopy. Glomerular volume was decreased in Li rats, with increased intra-individual variation. In all Li-rats, some glomeruli (mean 27%) were abnormal, with severe changes in only three rats. Ultrastructural parameters obtained by systematic sampling of three glomeruli in each rat showed no differences among groups. Among Li-treated animals there was a significant correlation between FPW and albumin excretion per unit filtration surface, and between filtration surface per glomerulus and inulin clearance. In conclusion, long-term lithium administration to newborn rats caused marked changes in glomerular volume which were not associated with measurable changes in structural parameters. No effect of ACEI-treatment was detectable. PMID- 11200821 TI - Resident aerobic microbiota of the adult human nasal cavity. AB - Recent evidence strongly suggests that the microbiota of the nasal cavity plays a crucial role in determining the reaction patterns of the mucosal and systemic immune system. However, little is known about the normal microbiota of the nasal cavity. The purpose of this study was to determine the microbiota in different parts of the nasal cavity and to develop and evaluate methods for this purpose. Samples were collected from 10 healthy adults by nasal washes and by swabbing of the mucosa through a sterile introduction device. Both methods gave results that were quantitatively and qualitatively reproducible, and revealed significant differences in the density of the nasal microbiota between individuals. The study revealed absence of gram-negative bacteria that are regular members of the commensal microbiota of the pharynx. Likewise, viridans type streptococci were sparsely represented. The nasal microbiota was dominated by species of the genera Corynebacterium, Aureobacterium, Rhodococcus, and Staphylococcus, including S. epidermis, S. capitis, S. hominis, S. haemolyticus, S. lugdunensis and S. warneri. These studies show that the microbiota of the nasal cavity of adults is strikingly different from that of the pharynx, and that the nasal cavity is a primary habitat for several species of diphtheroids recognized as opportunistic pathogens. Under special circumstances, single species, including IgA1 protease producing bacteria, may become predominant in a restricted area of the nasal mucosa. PMID- 11200822 TI - Strain differentiation in Bacteroides fragilis by RAPD and Dendron computer assisted gel analysis. AB - Batteroides fragilis is the anaerobe most frequently isolated from human infections. Strains of this species are not easily distinguished by phenotypic tests. It is important to make this distinction because virulence may vary between strains and because B. fragilis seems to be a heterogeneous species. The aim of this study was to assess the utility of randomly amplified polymorphic DNA (RAPD) analysis for differentiation of 46 strains of B. fragilis. Twenty-seven of the strains belonged to Johnson's DNA homology group I and 8 to group II, while 11 strains had not been assigned to any of these groups (NI group). The primers OPA16 and 18 were chosen among 30 primers tested for optimal RAPD analysis. OPA18 gave best discrimination, revealing a total of 15 genotypes while OPA16 gave 13. The gels obtained after RAPD analysis were evaluated with the Dendron computer assisted program. Most strains showed similarity levels (S(AB)) within 70%. Strain clusters thus established were not always in agreement with DNA homology since strains from both homology groups fell in the same cluster. Similarly, strains of the NI group fell among the group I and II homology strains. RAPD was useful for differentiation of B. fragilis strains and thus probably suitable for epidemiological studies. On the other hand, DNA-DNA homology, comparing the entire genome of strains rather than a few random priming sites, would be more reliable for taxonomy. Computer-assisted gel analysis made it possible to objectively evaluate multiple banding patterns, thereby increasing the reliability of the RAPD analysis. PMID- 11200823 TI - Complement activation reaches maximum during equilibrium between antigen and antibody in an in vitro model for thrombolysis with streptokinase. AB - Treatment with streptokinase (SK) of patients with acute myocardial infarction (AMI) is known to activate the complement system. In a previous investigation we found a great variation in the degree of complement activation taking place during infusion of SK in patients with AMI (range: 0-293% increase in pretreatment complement split product 3d (C3d) levels). In this in vitro study we added SK to serum with different concentrations of SK-antibodies (SK-Ab) and found that both the relative concentrations and the total concentrations of SK and Ab determined the degree of complement activation elicited by SK. This finding was in accordance with the Kendall-Heidelberger equation of antigen antibody equivalence. Furthermore, we found parallel rises in C3d and C4d, indicating that complement was activated via the classical pathway. A condition for maximal complement activation is antigen-antibody equivalence. PMID- 11200824 TI - Expression of topoisomerase II alpha, Ki-67 and p53 in early stage laryngeal carcinomas not featuring vocal cord fixation. AB - AIM: To determine whether topoisomerase II alpha (topoIIa) expression is an additional prognostic marker for less advanced stage laryngeal cancers first treated without surgery. Ki-67 and p53 protein levels were also assessed for comparison. EXPERIMENTAL DESIGN: Formalin-fixed, paraffin-embedded tumor material from 63 cases of squamous cell carcinoma (SCC) of the larynx (glottis, stages 0,1,2) was immunohistochemically stained for topoIIa, Ki-67 (MIB-1) and p53 (DO 7) and the results were compared with clinicopathologic findings. RESULTS: There were 7 stage 0 (TisN0M0), 33 stage I (T1N0M0), and 23 stage II (T2N0M0) SCCs with the TNM classification. Significant differences between carcinomas and normal mucosa were found for the topoIIa-LI, Ki-67-LI, and topoIIa-to-Ki-67 ratio. Regarding histologic grade, a significant difference in topoIIa-to-Ki-67 ratio was evident between well or moderately and poorly differentiated lesions. There were 19 cases of recurrence and 44 cases of nonrecurrence, but no significant differences were found for either of the indices or their ratio. No significant variation with p53 positivity was evident with reference to histologic differentiation, T-factor, clinical course, or proliferation. CONCLUSIONS: The results demonstrate that the topoIIa-to-Ki-67 ratio is a more sensitive parameter reflecting proliferation, for histologic grading of less advanced laryngeal SCCs, than topoIIa- or Ki-67-LIs. PMID- 11200825 TI - Genomic diversity of oral Candida krusei isolates as revealed by DNA fingerprinting and electrophoretic karyotyping. AB - Candida krusei is receiving increasing attention as an important human pathogen, especially in compromised patients, who frequently manifest with multiepisodes of candidosis. As there is scant information on the genetic diversity of this pathogen the present study was undertaken to establish its genetic profiles using three different typing methods: PFGE (pulsed-field gel electrophoresis), RFLP (restriction fragment length polymorphism), RAPD (randomly amplified polymorphic DNA). When 11 oral isolates of C. krusei were molecular typed by PFGE, 3 to 5 chromosomes with sizes ranging from 1000 kb to 3000 kb per isolate were revealed. All isolates produced a single bright band at approximately 1,100 kb and two to three bands between 2,500 kb and 3,000 kb, demonstrating 5 different karyotypes. RFLP with HinfI yielded 9 different genotypes, while DNA fingerprinting by RAPD with 3 primers (RSD6 (5'GCGATCCCCA3'), RSD7 (5'AGTGAATTCG CGGTGA-GATGCC3') and RSD12 (5'GCATATCAATAAGC GCAGGAAAAG 3')), resulted in 8, 3 and 11 different genotypes, respectively. This study provides evidence hitherto unavailable on the genetic polymorphism of C. krusei isolates colonizing the oral niche under different clinical conditions. Such genotypic polymorphism should help strain delineation in epidemiologic surveillance of either nosocomial or community outbreaks of C. krusei infections. PMID- 11200826 TI - Endothelial and epithelial expression of sialyl Lewis(x) in squamous carcinoma of the tongue. AB - In this retrospective study we describe the immunohistochemical expression pattern of sLe(x) epitopes in endothelial and epithelial cells of 59 squamous carcinomas of the tongue, and relate this to the relative survival rates of the patients. Endothelial sLe(x) expression was significantly elevated in malignant lesions compared to normal tissues, but did not have any prognostic value for the relative survival rate. In contrast, epithelial sLe(x) expression was decreased in carcinomas compared to normal tongue. The patients whose carcinoma showed only moderate epithelial HECA-452 reactivity had a significantly better relative survival rate than the patients with tumor specimens with neglible or very high HECA-452 reactivity. The epithelial staining with the two other anti-sLe(x) antibodies (CSLEX-1 and 2F3) did not correlate with the survival rates of tongue carcinoma patients. PMID- 11200828 TI - Expression of peroxisome proliferator activated receptors (PPARs) in human hair follicles and PPAR alpha involvement in hair growth. AB - Peroxisome proliferator-activated receptors (PPARs), which belong to the nuclear hormone receptor superfamily, have recently been described as potent key regulators of epidermal development. As 1,25-dihydroxyvitamin D3, retinoic acid and triiodothyronine are known to exert effects on skin and hair follicle growth through similar receptors, we decided to investigate both the expression pattern of the PPAR alpha, -delta and -gamma subtypes and their role in human hair follicles. Using reverse transcriptase-polymerase chain reaction and immunohistochemistry, we established that PPAR alpha, -delta and -gamma were expressed in both dermal and epithelial human hair follicle cells. Additionally, we evaluated the dose effect of clofibrate, a PPAR alpha ligand, on the survival of human hair follicles in culture. A beneficial effect was observed within a narrow range of concentrations. PMID- 11200827 TI - Superantigens and their association with dermatological inflammatory diseases: facts and hypotheses. AB - Superantigens have been suggested to play an important role in the pathogenesis of several inflammatory skin diseases as well as systemic diseases such as atopic dermatitis, psoriasis, vasculitis, T-cell lymphoma and autoimmune diseases. Infections often precede the onset and relapse of these diseases, and antibiotic treatment with or without additional glucocorticosteroids and immunoglobulins is occasionally successful. Superantigens are microbial proteins that are able to stimulate up to 20% of the naive T-cell population in a non-specific way. They are produced by gram-positive and -negative bacteria as well as by viruses, parasites and yeasts. The importance of the pathogenic role of superantigens is determined by the potency to induce inflammation by extensive cytokine release after T-cell stimulation and/or T-cell-mediated cytotoxicity and, thereby, tissue damage. Furthermore, superantigens may be able to induce autoimmune processes by stimulation of autoreactive T-cells as well as autoantibody production by stimulation of B-cells. Among the diseases associated with superantigens, atopic dermatitis, guttate and chronic plaque psoriasis, as well as Kawasaki disease, are by far the best-characterized. Nevertheless, conflicting results have been obtained and formal proof of a pathogenic role of superantigens in these diseases is still lacking. The aim of this review is to summarize the data on superantigens in terms of their distribution in microorganisms, their interactions with the adaptive immune system and their contribution to skin pathology. PMID- 11200829 TI - Prevalence of pigmented naevi in a Swedish population living close to the Arctic Circle. AB - The prevalence of common naevi and dysplastic naevi was investigated in a Swedish population with a low incidence of melanoma. A total of 201 subjects aged 30-50 years living in northern Sweden participated. The median number of common naevi per individual was 15, and 11% had dysplastic naevi. Higher numbers of common naevi were found in individuals with dysplastic naevi (median 68) and in those who had spent their childhood in southern Sweden (median 44). The prevalence of common naevi and dysplastic naevi was significantly lower than reported from a previously studied population in southern Sweden, with a melanoma incidence 4 times higher than in the north. The strong variability in naevus phenotype, and in melanoma incidence, between different regions of Sweden seems to be due to different levels of sun exposure rather than to differences in constitutional factors. PMID- 11200830 TI - Effect of EMLA cream on skin thickness and subcutaneous venous diameter. A randomized, placebo-controlled study in children. AB - EMLA cream, which is used to provide analgesia prior to venepuncture, induces a skin-blanching reaction. This reaction may be caused by both skin hydration and vasoconstriction. Twenty healthy children with veins suitable for venepuncture on the dorsa of the hands or at the antecubital fossae had applied either EMLA cream or placebo cream under occlusion for 60-70 min in a randomized, double-blind, cross-over study. An ultrasound examination of the skin was conducted. The mean percentage change in vein diameter after removal of EMLA cream was not significant whereas, 15 min after EMLA cream removal, the decrease in the initial vein diameter (13.5%) was significant (p<0.01). The mean percent increase in skin thickness after the removal of EMLA cream was also significant (19.3%; p=0.01). The changes in vein diameter and skin thickness due to the application of EMLA cream do not seem to be of clinical importance to vein cannulation. PMID- 11200831 TI - Intradermal buried vertical mattress suture as sole skin closure: evaluation of 149 cases. AB - Various buried suture techniques have been reported for dermatological surgery, but in most cases, superficial non-absorbable sutures are placed additionally. The aim of this study was to evaluate whether the intradermal buried vertical mattress suture can be safely used without additional skin suturing. Following 149 procedures in 126 patients, the colour and dehiscence of the scar and the presence of hypertrophy, granulomas or keloids were analysed. The cosmetic results were excellent to good in 78.5%, satisfactory in 19.5% and poor in 2%. Single additional superficial sutures had to be placed in only 14.7%. Suture marks were absent. Hypertrophic scarring was significantly more frequent in scars sutured with polyglactine than in scars sutured with polydioxanone. Early wound dehiscence, secondary wound healing and infection due to missing superficial skin sutures did not occur. This suture technique is safe, easy and fast to perform, and achieves good cosmetic results without leaving suture marks. PMID- 11200832 TI - Longitudinal case analysis in atopic dermatitis. AB - The current knowledge on atopic dermatitis comes mainly from cross-sectional studies, which are not suited to establish time-courses or causal links in complex diseases. As an alternative approach, the method of longitudinal case analysis by the autoregressive integrated moving average (ARIMA) method has been introduced to investigate the pathogenesis of atopic dermatitis. The method was applied to the investigation of 2 patients suffering from severe and moderate atopic dermatitis. Disease activity, peripheral blood parameters (differential blood count, lymphocyte subpopulations, immunoglobulin E, eosinophilic cationic protein, soluble interleukin-2 receptor), mental stress and environmental factors were determined daily for 50 days. Both patients showed a positive correlation between CD4+ and CD25+ T-cells, a negative correlation between CD16/56+ natural killer cells and CD4+ T-cells, a negative correlation between eosinophils and polymorphonuclear leukocytes, and a time-shifted positive correlation of up to 2 days between scores quantifying mental stress and disease activity. A positive correlation between T-cells and polymorphonuclear leukocytes, CD4+ T-cells and the CD45RA+ subtype, as well as a negative correlation between stress and eosinophils, sports and eosinophils, and sports and disease activity were found only in one patient with more severe atopic dermatitis. In conclusion, longitudinal time-series analysis might represent an interesting and adequate method to generate and test new hypotheses on biomedical problems which cannot be addressed by cross-sectional studies. PMID- 11200833 TI - Prevalence of atopic dermatitis in Korea. AB - This study was designed to estimate the prevalence and personal or family history of atopic dermatitis in school children in 3 areas of Korea: urban (Seoul), industrial (Ulsan) and rural (Chunchon). On the basis of dermatologists' physical examinations and the questionnaires completed by parents or guardians, the prevalence of atopic dermatitis was estimated to be 3.3% in the industrial area, 6.6% in the rural area and 7.8% in the urban area. The frequency of atopic dermatitis decreased with age and was significantly lower in the industrial area than in the rural and urban areas. PMID- 11200834 TI - IgE antibodies to Malassezia furfur, M. sympodialis and Pityrosporum orbiculare in patients with atopic dermatitis, seborrheic eczema or pityriasis versicolor, and identification of respective allergens. AB - Malassezia yeasts may be a trigger factor for atopic dermatitis. Following the recent reclassification of the genus, the presence of specific IgE antibodies was examined in the sera of patients with atopic dermatitis (n = 223), pityriasis versicolor (n = 83), seborrheic eczema (n = 50) and hymenoptera allergy (n = 39) and in controls without skin diseases (n = 50). In addition to using the commercially available radioallergosorbent test (RAST) for Pityrosporum orbiculare couplings were also made against the reference strains for M. furfur and M. sympodialis. To characterize the specificity and molecular weight of corresponding epitopes identical material was used for production of an immunoblot. Despite high total levels of IgE, controls and patients with pityriasis versicolor showed no specific IgE antibodies. Six patients (12%) with seborrheic eczema were positive while 78 patients (35%) with atopic dermatitis had specific IgE antibodies in higher RAST classes that differed between the Malassezia species. The molecular weights of the main antigens of M. sympodialis and M. furfur were determined to be 15, 22, 30, 37, 40, 58, 79, 92, 99 and 124 kDa and 15, 25, 27, 43, 58, 92, 99 and 107 kDa, respectively. Evaluated according to the location of their disease, patients with head and neck lesions most frequently showed Malassezia-specific IgE antibodies. However, there were differences between the Malassezia species tested, the previously used strain P. orbiculare being assignable to the species M. sympodialis. PMID- 11200835 TI - Long-term serological follow-up of patients treated for chronic cutaneous borreliosis or culture-positive erythema migrans. AB - The kinetics of antibodies to Borrelia burgdorferi following successful treatment of early and late cutaneous borreliosis were analysed in consecutive serum samples by an enzyme-linked immunosorbent assay (ELISA) technique. Twenty-three patients with culture positive erythema migrans were followed for 23+/-14 months: 41% stayed seronegative, 35% showed an isolated immunoglobulin M (IgM) response, 8% an isolated IgG response and 16% a combined IgM and IgG responses. In general, antibody levels peaked within the first 3 months of symptom onset, whereafter a gradual decline was observed within 1 year. Twenty-two patients with chronic cutaneous borreliosis were followed for 23+/-11 months and all patients stayed IgG positive. Nearly three-quarters showed a clear decline in IgG levels over the years, while the rest did not. After 9+/-1 years 88% of 16 patients examined were still IgG positive. In conclusion, treatment of erythema migrans should be initiated on clinical appearance as a substantial number of patients stayed seronegative. Treatment success may in part be monitored serologically for both seropositive erythema migrans and chronic cutaneous borreliosis as most patients show declining titres after successful treatment. However, continuously high titres do not necessarily indicate treatment failure. PMID- 11200836 TI - Primary cutaneous B-cell lymphomas of the lower limbs: a study of integrin expression in 11 cases. AB - Primary cutaneous B-cell lymphoma is a rare disease. Among the cutaneous B lymphomas, B-cell lymphomas of the lower limbs appear as a special subgroup with a prognosis that is possibly worse than that of primary cutaneous B-cell lymphomas located on the trunk, arms or head, with more frequent relapses. In addition, some recent studies indicate that the level of expression of integrins on tumour cells could be related to the clinical course of the disease. This study reports on 14 cases of primary cutaneous B-cell lymphomas of the lower limbs and their clinical course. A study of integrin expression by tumour cells was performed in 11 of these cases. With a mean follow-up of 31 months, the study confirmed the worse prognosis of lymphomas with a predominance of centroblasts and immunoblasts (3 deaths) compared with lymphomas with a predominance of centrocytes, as well as their higher rate of recurrence (7/11). A correlation was confirmed between the course of the disease and the level of expression of lymphocyte function-associated antigen-1, intercellular adhesion molecule-1 and very late antigen-4 by tumour cells. PMID- 11200837 TI - Onychomatricoma with misleading features. AB - Onychomatricoma is a rare tumour of the nail matrix with peculiar clinical and histological features and electron microscopic findings. We report on 5 cases with appearances which were misleading. Three presented as longitudinal melanonychia, a previously unreported observation. One case had the appearance of a cutaneous horn. In 3 of the 5 cases the tumour was associated with an onychomycosis and this may thus have been a predisposing factor in the secondary fungal infestation. Onychomatricoma appears as a multi-faceted tumour which can be mimicked by longitudinal melanonychia and/or onychomycosis. PMID- 11200838 TI - Lupus erythematosus panniculitis in a patient with autoimmune hepatitis. AB - Lupus erythematosus panniculitis (profundus), a rare variant of chronic panniculitis, sometimes develops during the course of discoid lupus erythematosus or systemic lupus erythematosus. A 61-year-old woman had suffered from autoimmune hepatitis type I for 5 years. Prednisolone had been administered as maintenance therapy and her hepatitis had been well controlled. However, asymptomatic erythematous indurated nodules developed symmetrically in both pre-auricular regions, and skin biopsy revealed lupus erythematosus panniculitis (profundus). Increase in dosage of prednisolone resolved the skin lesion, leaving depressed atrophic scars. This is the first report of lupus erythematosus panniculitis complicating autoimmune hepatitis. PMID- 11200839 TI - Coexistence of xeroderma pigmentosum with sarcoidosis and adenocarcinoma of the digestive organs. AB - Xeroderma pigmentosum has not been reported in association with any specific diseases except for skin malignancy. We observed a case of its coexistence with sarcoidosis and adenocarcinoma of the digestive organs, which has been reported only once in the past. A 54-year-old Japanese female with a variant type of xeroderma pigmentosum developed successively multiple lesions of basal cell carcinoma and squamous cell carcinoma on her face. Intensive metastasis studies led to the incidental detection of non-caseating epithelioid cell granulomas in one of the palpable right supraclavicular lymph nodes. Similar granulomas were also revealed in the excised tissue specimen of squamous cell carcinomas of her left cheek. She was also found to have bilateral hilar lymphadenopathy and chronic uveitis. Three years later, she died of colon adenocarcinoma and its liver metastasis. PMID- 11200840 TI - A two-step schedule for the treatment of actinomycotic mycetomas. AB - Actinomycotic mycetomas usually respond slowly to treatment with antibiotics. In an attempt to hasten clinical resolution, we used a 2-step regimen consisting of an intensive phase of therapy with penicillin, gentamycin and co-trimoxazole for 5-7 weeks, followed by maintenance therapy with amoxicillin and co-trimoxazole. Seven patients were treated, all of whom showed significant reduction in discharge and swelling after the intensive phase. Maintenance therapy was continued for 2-5 months after the lesions became completely inactive. Five patients completed maintenance therapy, which was given for 6-16 months (mean 10.7 months), and remained free of disease during a mean post-treatment follow-up period of 6.4 months. The other 2 patients also responded satisfactorily and continue to receive maintenance therapy. Side-effects necessitating a modification of the treatment schedule occurred in 2 patients but reversed on discontinuation of the drugs responsible. This treatment schedule produces a rapid clinical response during the initial, intensive phase and promotes compliance with the longer maintenance phase of treatment necessary to achieve a complete cure. PMID- 11200841 TI - Treatment of multiple basal cell carcinomas in the scalp with imiquimod 5% cream. PMID- 11200842 TI - Psoriasiform eruption and anticonvulsant drugs. PMID- 11200844 TI - Acquired reactive perforating collagenosis triggered by scabies infection. PMID- 11200843 TI - Plasma vascular endothelial growth factor levels in scleroderma are not correlated with disease activity. PMID- 11200845 TI - Acyclovir prophylaxis of recurrent herpes labialis before electrolysis. PMID- 11200846 TI - An unusual severe case of subcorneal pustular dermatosis treated with cyclosporine and prednisolone. PMID- 11200847 TI - Woolly hair associated with loose anagen hair. PMID- 11200848 TI - Leukotriene inhibitor may be effective in treatment of psoriasis. PMID- 11200849 TI - UVA1 cold-light phototherapy of small plaque parapsoriasis. PMID- 11200850 TI - Zosteriform metastasis of occult bronchogenic carcinoma. PMID- 11200851 TI - Lethal pancytopenia associated with chilblain lupus erythematosus. PMID- 11200852 TI - An unusual cause of vascular purpura: recurrent cutaneous eosinophilic necrotizing vasculitis. PMID- 11200853 TI - Hypercalcemia of malignancy associated with trichilemmal carcinoma in burn scar. PMID- 11200854 TI - Urticaria after administration of alendronate. PMID- 11200855 TI - Acanthosis nigricans with atypical localization. PMID- 11200856 TI - [Intersubjectivity and interpersonal relations of schizophrenics]. AB - Original accounts of an introspectively and linguistically highly gifted schizophrenic woman serve as a means to reflect about the meaning of the concept of intersubjectivity in the sense of Husserl, the constitution of self and world and its failure in the schizophrenic ego disorder. Concerning general psychopathology, there can be attempted to propose a typology of disordered intersubjectivity and consequently interpersonality. Psychotherapy of schizophrenics means reconstruction of intersubjectivity. PMID- 11200857 TI - [Psychoeducational intervention for schizophrenic patients and subsequent long term ambulatory care. A four-year follow-up] . AB - A subset of schizophrenic inpatients and families participated in an eight sessions bifocal psychoeducational intervention, followed by treatment in a corresponding outpatient department. These patients were a part of the multicenter and randomized Munchner Psychosis-Information-Project (PIP). The course of illness in 88 patients treated in the outpatient department of the Technical University of Munich has been recorded in a 4-year follow-up study. 60% of the patients continued outpatient treatment while 40% lost contact with the outpatient department. Predictors for patient drop-out were assessed and the course of illness of both groups was compared. There was no significant difference between the relapse rate of the patients who dropped out (66%) and those who continued the long-term treatment (53%). However, within the 4-year period the drop-out patients had more than twice as many hospital days compared to the patients who maintained the outpatient treatment. The improved social adjustment and quality of life of these patients, along with the 50% reduction of readmission days demonstrates the impact of the long-term treatment in this study. PMID- 11200858 TI - [Weight gain from atypical neuroleptics--an underreported adverse effect?]. AB - After the introduction of the so-called "atypical neuroleptics" in the clinical experience a marked weight gain was frequently observed in patients treated with some of these agents. In this review the frequency, amount and conditions of weight gain during the medication with 'atypical' neuroleptics were evaluated. A comparison is limited by the different designs and recruitment procedures of the reviewed studies. The available data show that the frequency as well as the amount of weight gain is particularly high in patients treated with clozapine, olanzapine, and likely also quetiapine and zotepine. Moderate changes of weight have been observed in the treatment with risperidone and probably also with amisulpride, while ziprasidone seems to induce only clinically irrelevant weight changes. Weight gain most frequently occurs in the first weeks of treatment. Underweighted patients are at highest risk to gain weight. The underlying pathomechanism still remains widely unclear. The relative receptor affinities of the atypical antipsychotics for histamine H1 as well as their quotient of 5 HT2/D2 receptor affinity appear to be a correlate of weight gain. Furthermore, the induction of leptin secretion may have an important impact on weight gain in subjects treated with atypical neuroleptics. Although many questions concerning the conditions of weight gain remain unsolved, this side-effect has to be considered in the medication with many atypical neuroleptics, particularly in view of compliance in long-term treatment and possible medical complications. PMID- 11200859 TI - [Expectations and satisfaction of social-psychiatric services regarding their collaboraton with the psychiatric hospital] . AB - OBJECTIVE: Collaboration with the psychiatric hospital should be investigated from the viewpoint of social-psychiatric services (SpDi). METHODS: Based upon a content analysis of interviews with staff members of all social-psychiatric services working in the catchment area of a psychiatric hospital, a questionnaire was developed which consists 32 Items assessing expectations and satisfaction in 6-step Likert-type scales. RESULTS: Response rate was 80% (n = 40). SpDi's staff express high expectations to psychiatric hospital. They assess good inpatient treatment, patient's information about treatment, SpDi's involvement in discharge planning, patient's attendance at SpDi's consulting in the hospital, and networking of psychiatric institutions to be very important. Differences between expectation and satisfaction especially refer to information of SpDi about client's admission, SpDi's involvement in discharge planning, and knowledge of hospital staff about social-psychiatric services. CONCLUSIONS: Evaluation of expectations and satisfaction of SpDi as an important partner of the psychiatric hospital allows conclusions for quality assurance of psychiatric care and offers concrete clues for a better collaboration at the interface of out-patient and in patient care being advantageous for patients. PMID- 11200861 TI - [Klosterkotter J, Hellmich M, Schulze-Lutter F. Is the diagnosis of schizophrenic disorders already in the inital prodromal phase before the first psychotic manifestation results? Fortsch Neurol Psychiat 2000; 68: S13-S21] . PMID- 11200860 TI - [Sexuality and partnership aspects of Parkinson disease. Results of an empirical study of patients and their partners] . AB - In a retrospective, non-randomised cross-sectional study the influence of Parkinson's Disease (PD) on sexuality and partnership in 2099 affected members of the German Parkinson Organization (dPV) were investigated. At an average age of 65, 330 women and 1008 men had been living in partnership for an average of 37 years. Not only sexual dysfunctions occurred both in affected women and men but also an evident reduction of sexual contentment on the whole. The affected patients mentioned specific symptoms of PD and medication as the decisive factors of influence on their sexuality. It was impressive that one single group of substances could influence sexual functions by increasing as well as decreasing them or having no influence at all. Furthermore different sexes in different genders became obvious. The information concerning their partnership situation given by both men and women shows that communication in general, especially caressing and showing feelings, are reduced since diagnosis, whereas a desire for mutual intimacy prevails on the same level as before. PMID- 11200862 TI - Prevalence of persistent asymptomatic proteinuria in HIV-infected outpatients and lack of correlation with viral load. AB - AIM: Human immunodeficiency virus-associated nephropathy (HIVAN) is projected to be a leading cause of end-stage renal disease (ESRD) in young African American men in the new millennium. Little is known about the early natural history of the disease, including the prevalence of asymptomatic nephropathy. The primary aim of this study was to define the prevalence of persistent asymptomatic proteinuria in a contemporary, ambulatory human immunodeficiency virus- (HIV) infected population. The secondary aim was to correlate the presence of persistent proteinuria with measures of HIV disease. METHODS: Using a readily available screening tool, the urine dipstick, we determined the prevalence of persistent asymptomatic proteinuria in the outpatient VA Connecticut (VA CT) Healthcare System West Haven HIV Clinic population. We compared the presence of persistent proteinuria with measures of HIV viral disease. RESULTS: The prevalence of persistent asymptomatic proteinuria was 14% (7 of 49 patients). The presence of persistent proteinuria was not correlated with viral load. CONCLUSIONS: A significant prevalence of occult renal disease exists in the asymptomatic HIV seropositive outpatient population and is not correlated with viral load. PMID- 11200863 TI - Focal segmental glomerulosclerosis in children from KwaZulu/Natal, South Africa. AB - AIM: The aim of this paper was to describe the clinical course, histological grading, response to therapies and complications of nephrotic children with focal segmental glomerulosclerosis (FSGS) in Durban, South Africa. METHODS: The demographic data, response to drug therapy, complications, renal function and disease status at the last hospital visit were recorded in children diagnosed as FSGS on histology. Biopsies were graded according to the degree of glomerulosclerosis and interstitial involvement. RESULTS: Seventy-five children, 32 Indian and 43 Black were studied. FSGS as a proportion of all children seen with nephrotic syndrome, has risen between 1970 to 1995 from 1.8% to 20% in Indian children and 5% to 28% in Black children. Of those children followed for two years or more, the two racial groups were similar with respect to age at presentation, gender, histological grading, hypertension, renal outcome and response to therapies except for cushingoid features (p < 0.7), alopecia (p < 0.003) and respiratory tract infections (p < 0.001) which occurred more frequently in Indian children. Forty-three children were followed for between 2 16 years: 14 (10 Indian and 4 Black (p < 0.5)) (29%) had grade 1 changes, 24(13 Indian, 11 Black (p < 0.98)) (56%) had grade 2 changes, 3 (Indian (p < 0.26)) (7%) had grade 3 changes and 2 (Black (p < 0.17)) grade 4 changes. Over this period 27 (63%) had normal renal function, 6 (14%) died, 4 (9%) developed impaired renal function, 6 (14%) chronic renal insufficiency and 6 (14%) end stage renal disease. Three of the latter were transplanted. At the last hospital visit, Indian children had remitted more often (p < 0.6) and Black children suffered relapse more frequently (p < 0.03). Two children had spontaneous disease remission, and 5 had sustained remission following a course of prednisolone and/or cyclophosphamide. CONCLUSION: This, one of the largest studies of FSGS in children, shows a marked rise in this condition and some differences between Indian and Black children. The outcome in Black children was not as poor as anticipated. PMID- 11200864 TI - Membranous nephropathy associated with hepatitis B in Spanish children. AB - AIM: To examine retrospectively long-term evolution and treatment of pediatric membranous nephropathy (MN) cases associated with hepatitis B (HB) in the hospital "La Paz". MATERIAL AND METHODS: The clinical records of 12 children diagnosed with HB-associated MN in our hospital between 1970 and 1996. RESULTS: All patients were positive for hepatitis B surface antigen (HBsAg); 6 were tested for hepatitis Be antigen (HBeAg) and were also positive. At onset, all of them had proteinuria (8 in nephrotic range), 6 had microscopic hematuria and 4 macroscopic hematuria. Seven of 8 children who started with a nephrotic syndrome received steroids and all of them were steroid-resistant. After 9.95 +/- 5.88 years of follow-up, renal function remained normal and proteinuria and hematuria have disappeared in all of them. A family study for hepatitis B was carried out in 8 cases and 7 of them were positive. Only in one case vertical transmission was demonstrated; this patient remained HBeAg positive. In 7 patients, hepatic biopsy was performed: 3 had a chronic active hepatitis, 3 a persistent chronic hepatitis and one a residual acute hepatitis. CONCLUSIONS: Membranous nephropathy is a rare pediatric disease in our area and most of the cases are related to hepatitis B (HB). The outcome was excellent with and without treatment but all of them remained HBsAg positive. PMID- 11200865 TI - Development and validation of a disease extent index for Wegener's granulomatosis. AB - AIMS: The quantitative assessment of disease extent (staging) and activity (grading) in patients with ANCA-associated vasculitides is one prerequisite for the comparison of outcomes in different patient cohorts. We present a validation study of the Disease Extent Index (DEI). METHODS: 66 patients with Wegener's granulomatosis were examined to assess the validity, reliability and sensitivity to change of the DEI. Correlation coefficients were calculated to estimate associations between DEI and BVAS (Birmingham Vasculitis Activity Score), a previously established activity score, and between DEI and serological markers. RESULTS: Among patients with active disease, DEI correlated significantly with cANCA titer (r = 0.46), leukocyte count (r = 0.38) and platelet count (r = 0.53). Among patients in remission, DEI correlated significantly with cANCA titer (r = 0.61), CRP (r = 0.47) and sIL2R (r = 0.47). Additionally, a high association of DEI and BVAS (r = 0.9) confirmed a rather high convergent validity. The effect size of DEI equals 2.37 standard deviation units and indicates a considerable change from active disease to remission. CONCLUSIONS: The DEI is valid, reliable, easy, quick to perform and highly reproducible. Although it correlates with some surrogate markers of disease activity and the BVAS, the DEI quantifies different domains of the disease than the BVAS and should therefore be used in conjunction with the BVAS. PMID- 11200866 TI - Deterioration in renal function associated with fibrate therapy. AB - BACKGROUND: Fibric acid derivatives (fibrates) are commonly used for the treatment of hyperlipidemia. A side-effect of these medications that is not well recognized is deterioration in renal function during therapy. This study reviewed a series of patients who showed such a deterioration. METHODS: The design was a retrospective chart review. Data extracted included creatinine, urea, cyclosporine levels, medical history, and medications. Charts were examined for other potential reasons for a change in creatinine. RESULTS: There were a total of 10 patients. All were males between the ages of 37 and 71. All had a history of renal insufficiency. Six had received a renal transplant and, of these, 5 were on cyclosporine. Reasons for underlying renal impairment included diabetes, hypertension, nephrosclerosis, and renal disease of unknown etiology. Most patients had risk factors for or the presence of vascular disease. The mean pre treatment creatinine was 182 +/- 14 micromol/l (2.1 +/- 0.2 mg/dl) (mean +/- SE), compared to a peak creatinine on the medication of 247 +/- 16 micromol/l (2.8 +/- 0.2 mg/dl) (p < 0.001). The post-medication mean was 183 +/- 13 (2.1 +/- 0.1 mg/dl) (p < 0.001 vs maximum creatinine). Urea values also increased with therapy and decreased following discontinuation of the fibrate. Cyclosporine levels did not change with treatment. All recorded creatine kinase values were within the normal range. CONCLUSIONS: A group of 10 men showed a reversible deterioration in renal function while being treated with a fibrate for hyperlipidemia. The mechanism involved in the deterioration in renal function is not clear. The most plausible mechanism is one based on renal hemodynamics, given the rapid and complete reversibility that was noted and the finding that most patients had risk factors for vascular disease. If patients with pre-existing renal dysfunction are to receive a trial of fibrate therapy, this should be done with caution and PMID- 11200867 TI - The effect of trimethoprim on potassium and uric acid metabolism in normal human subjects. AB - BACKGROUND: Trimethoprim used in combination with other antibiotics, has been implicated in causing hyperkalemia and hypouricemia in patients with acquired immune deficiency syndrome (AIDS). In experimental animal models, trimethoprim has been demonstrated to block sodium channels and Na+-K+-ATPase in the distal nephron and thus impair potassium excretion. Although the data from the experimental models suggest that trimethoprim reduces urinary potassium excretion, the retrospective clinical studies have confounding factors that prevent a rigorous demonstration that the hyperkalemia and hypouricemia are due solely to the effects of trimethoprim on solute excretion. AIM: The purpose of this study was to evaluate the effect of trimethoprim on potassium and uric acid balance in normal human subjects. METHODS: Five normal human subjects were admitted to the general clinical research center and placed on a fixed metabolic diet. After a 4-day control period, the subjects were given trimethoprim (15 mg/kg/day) orally for 5-7 days followed by a 4-day recovery period. Free-flow blood samples and 24-hour urine collections were obtained daily. RESULTS: Treatment with trimethoprim resulted in a significant increase in plasma potassium concentration (4.5 +/- 0.1 versus 3.7 +/- 0.1 mmol/l, p < 0.005) and significant decrease in serum uric acid concentration (3.8 +/- 0.4 versus 5.6 +/- 0.5 mg/dl, p < 0.001). Treatment with trimethoprim significantly increased the urinary excretion of uric acid, but did not significantly decrease potassium excretion during the 7-day treatment period. There was, however, a significant decrease in potassium excretion observed during the first 48 hours of trimethoprim treatment. In one subject where repeat studies were performed using different dosages, the effect on potassium and uric acid levels appeared to be dose-dependent. CONCLUSIONS: Trimethoprim increases plasma potassium concentration probably by reducing urinary potassium excretion. Trimethoprim decreases serum uric acid levels by augmenting urinary uric acid excretion. This uricosuric effect may be due to the ability of trimethoprim to impair urate reabsorption by the urate-anion exchanger in the proximal tubule. PMID- 11200868 TI - Expression of basic helix-loop-helix proteins in the glomeruli. AB - BACKGROUND: Basic helix loop helix (bHLH) proteins play a critical role in the differentiation of not only striated muscle cells but also adipocytes, neuron cells and smooth muscle cells. Previous studies have established in vitro mouse mesangial cells (MCs) to maintain the differentiated smooth muscle phenotype. MATERIALS AND METHODS: The purpose of the present study was to clone bHLH proteins from these MCs using the primers designed from a homologous sequence specific to bHLH, and to analyze the presence of bHLH proteins in normal kidney in vivo. From the cloning of MCs in vitro, we identified myf5 and herculin mRNA but not myoD. The expression of bHLH proteins in vivo was examined by immunohistochemistry with each specific antibody. RESULTS: The MCs in newborn mice possessed Id but did not express either protein herculin or myoD. On the other hand, mature MCs expressed both myf5 and herculin. The Id protein disappeared in mature glomeruli. CONCLUSION: These results suggest that bHLH proteins are an important factor for mature MCs in vivo. PMID- 11200869 TI - Potassium citrate administration ameliorates tubulointerstitial lesions in rats with uric acid nephropathy. AB - Although controversial, chronic uric acid nephropathy is a tubulointerstitial disease capable of developing renal function loss. On the other hand, potassium citrate (KCi) administration has demonstrated to be effective in calcium as well as uric acid nephrolithiasis therapy. Therefore, the aim of the present study was to evaluate the possible benefit of KCi treatment in the prevention or amelioration of renal interstitial damage in uric acid nephropathy. Two-month-old male Sprague-Dawley rats were divided into 3 groups: G1 hyperuricemic (HU), G2 hyperuricemic + KCi (HU+KCi), and G3 KCi. G1 and G2 were fed on oxonic acid (inhibitor of rat liver uricase), and a uric acid supplement, during 4 weeks. G2 and G3 were given 2% KCi in drinking water, and G1 regular tap water and standard rat chow. At the end of the study, renal tissue was processed for light and electron microscopy and immunostaining by alpha-smooth muscle actin (SMA). Tubulointerstitial lesions and the amount of alpha-SMA immunostaining in renal tissue were evaluated by histomorphometric quantitation. Rats belonging to the hyperuricemic groups treated with KCi (G2) showed fewer tubulointerstitial lesions as follows: % tubular atrophy: 1.7 +/- 0.3 versus 7.2 +/- 1.2, p < 0.05; inflammatory cells infiltrate (number of cells/area): 0.6 +/- 0.1 versus 2.4 +/- 0.2, p < 0.01; % interstitial fibrosis (cortex): 3.3 +/- 0.3 versus 9.3 +/- 0.5, p < 0.05; % interstitial fibrosis (medulla): 5.2 +/- 0.3 versus 21.9 +/- 1.2, p < 0.01, lower albuminuria (32.8 +/- 11.2 mg/day versus 128.5 +/- 10.4, p < 0.01), higher creatinine clearance ( 1.36 +/- 0.02 ml/min versus 0.74 +/- 0.01, p < 0.01 ) and less percentage of alpha-SMA in renal tissue (1.8 +/- 0.1 versus 10.5 +/- 1.4, p < 0.05), when compared with the hyperuricemic group not treated with KCi (G1). These data suggest that KCi administration could provide a substantial benefit in the regard to tubulointerstitial lesion and progressive renal damage. PMID- 11200870 TI - Chronic cyclosporin-induced nephropathy. AB - AIMS: There is still no consensus about the prognostic influence of chronic nephropathy induced by low-dose maintenance therapy with cyclosporin. Our aim was to investigate the prognostic effect of cyclosporin nephropathy in Japanese renal transplant recipients. MATERIAL: We retrospectively investigated the clinical records of 1,323 kidney transplant recipients who received cyclosporin at 65 institutions in Japan from 1982 to 1991. METHOD: Renal biopsy was performed in 461 patients. RESULTS: At 5 years and 9 years after transplantation, the patients who had cyclosporin nephropathy associated with immunological rejection, glomerulonephritis, or both showed a significantly worse prognosis than those with cyclosporin nephropathy alone (p < 0.01). There was no significant difference in the loss of renal function at 9 years after transplantation between patients showing no abnormalities and patients with cyclosporin nephropathy alone. Even when cyclosporin nephropathy was absent, the long-term prognosis was unfavorable in recipients with immunological rejection or glomerulonephritis. CONCLUSIONS: These results suggest that cyclosporin nephropathy does not influence the prognosis of renal transplantation in patients on low-dose maintenance therapy with cyclosporin. PMID- 11200871 TI - Albuminuria and the renin-angiotensin system gene polymorphisms in type-2 diabetic and in normoglycemic hypertensive Chinese. AB - BACKGROUND: Albuminuria predicts nephropathy-related mortality in Caucasian and Chinese populations. The involvement of renin-angiotensin system (RAS) gene polymorphisms in the pathogenesis of nephropathy has been described predominantly in Caucasian populations. We have previously suggested that the angiotensinogen 235T variant may be associated with nephropathy in diabetic Chinese. PATIENTS AND METHODS: To validate these findings and extend them to include non-diabetic nephropathy, we examined the association of albuminuria and gene polymorphisms of the angiotensinogen M235T, angiotensin-converting enzyme insertion/deletion and angiotensin II type I receptor A1166C polymorphisms in 614 Chinese subjects (66% type 2 diabetic, 16% normoglycemic hypertensives and 18% controls). RESULTS: Obesity and higher blood pressure were associated with albuminuria in both diabetes and normoglycemic hypertension. In the diabetic group, albuminuria was also associated with increased insulin resistance and glycemic indices, duration of diabetes and adverse lipid profiles. Only the ACE gene polymorphism showed evidence of association with albuminuria, with the D allele being less frequent in the normoglycemic hypertensive patients with albuminuria (25.0%) than the controls (41.4%) or normoalbuminuric group (39.6%) and in those hypertensives at increased risk (albumin-to-creatinine ratio > 5.6 mg/mmol) of end-stage renal disease than those at lower risk (all p < 0.05), but not in the diabetic group. The D allele was also less prevalent in the total (31.9%) and normoalbuminuric (32.2%) diabetic groups than in the controls (p < 0.05). CONCLUSION: In this cohort of Chinese subjects, the ACE gene polymorphism D allele was less frequent in normoglycemic hypertensive patients with albuminuria and in type 2 diabetes. PMID- 11200872 TI - Coexistence of Fabry's disease and necrotizing and crescentic glomerulonephritis. AB - The coexistence of Fabry's disease, an X-linked hereditary disease, and other renal diseases, has rarely been described in the same patient. Combined Fabry's disease and pauci-immune necrotizing and crescentic glomerulonephritis (NCGN) is hitherto unreported. We present the clinical and pathologic data of two patients with combined Fabry's disease and NCGN. Both patients presented with fevers of unknown origin and progressive renal insufficiency, however, lacked any other pathognomic signs of Fabry's disease such as acroparesthesias, dyshidrosis, and cutaneous angiokeratomas. The possible pathogenic mechanisms and causal relationship between the two disease processes are discussed. PMID- 11200874 TI - A reply to Schuck et al. Calculation of water deficit in a patient with hypernatremia. PMID- 11200873 TI - Trimethoprim-sulfamethoxazole induced aseptic meningitis in a renal transplant patient. AB - A 45-year-old man underwent renal transplant for end-stage renal disease complicating systemic lupus erythematosis. Within 24 hours of initiating Pneumocystis carinii pneumonia (PCP) prophylaxis with trimethoprim sulfamethoxazole (TMP-SMX) he developed fever and confusion. Cerebrospinal fluid examination revealed a pleocytosis but cultures were negative. The patient improved within three days after cessation of the TMP-SMX but symptoms recurred rapidly upon drug rechallenge. Drug-induced aseptic meningitis is an uncommon but well described clinical entity. This is the first case described in a patient following renal transplantation. The literature is reviewed and the clinical features, diagnostic challenges and possible mechanisms of TMP-SMX-induced aseptic meningitis are discussed. This problem may be more common in the transplant population than is recognized given the difficulty of diagnosis combined with the widespread use of TMP-SMX as PCP prophylaxis. PMID- 11200875 TI - A reply to Sezer et al. Diagnosis of AL amyloidosis. PMID- 11200876 TI - Newer immunomodulating drugs in rheumatoid arthritis may precipitate glomerulonephritis. PMID- 11200877 TI - Blurred vision as chief complaint in nephropathia epidemica. PMID- 11200878 TI - RPA recommendations to improve accreditation of dialysis facilities. Renal Physicians Association. PMID- 11200879 TI - Alternative methods for the production of carrier-free (66,67)Ga. AB - Heavy ion activation of natural cobalt foil with 52 MeV 11B4+ and 73 MeV 12C6+ results in the formation of carrier-free (66,67)Ge and (66,67)As radionuclides, respectively, along with their corresponding decay products, (66,67)Ga in the matrix. The carrier free gallium radionuclides have been separated from the bulk target matrix cobalt by employing liquid-liquid extraction method using TOA as liquid anion exchanger. PMID- 11200880 TI - Multitracer techniques: applications in chemical and life sciences. AB - The scope and approaches of the "multitracer technique" have briefly been reviewed. The various aspects of the "multitracer technique" include, the methods of accelerator production of "multitracers" and their separation, the application of this technique in the study of adsorption of metal ions on solid surfaces and in the study of distribution of trace elements in plants and animals. PMID- 11200881 TI - An admonition when measuring the lipophilicity of radiotracers using counting techniques. AB - Log P measurements are a fundamental physico-chemical parameter and one of the cornerstones of structure activity relationships in medicinal chemistry. Despite the attractiveness of the method, the use of counting techniques to measure the log P of lipophilic radiotracers is fraught with pitfalls due to the amplifying effects of small quantities of radioactive impurities. For example, a radiotracer with a log P of 4 containing only 0.1% of a radioactive impurity with a log P of 1 will have an apparent log P of 3 if measured using conventional shake-flask partition techniques, counting the radioactivity in each phase. However, pre washing the radiotracer-containing organic phase with aqueous phase can, in many cases, allay doubts about the validity of such measurements. PMID- 11200882 TI - Sorption and diffusion behavior of Cs and Sr on Jih-Hsing bentonite. AB - Sorption and diffusion are important processes for the transport of radionuclides through buffer materials such as bentonite. In this study, the sorption and diffusion behaviors of Cs and Sr on Jih-Hsing bentonite are investigated using batch and through-diffusion techniques. The distribution coefficients (Kds) of Cs and Sr from batch experiments are approximately 1200 ml/g and 800 ml/g, respectively. It is found that the Freundlich isotherm model could fit the sorption isotherm with an equilibrium concentration of 10(-7)-10(-1) N. The calculated retardation factors (Rds) for samples at densities of 1.8 g/cm3, 2.0 g/cm3 and 2.2 g/cm3 are 5685, 7744, and 11000 for Cs, and are 3790, 5162, and 7334 for Sr. For the through-diffusion experiments on the compacted samples with the same densities, the corresponding apparent diffusion coefficients for Cs are (2.83+/-0.75) x 10(-13) m2/s, (1.97+/-0.02) x 10(-13) m2/s, and (1.91+/-0.12) x 10(-13) m2/s, respectively. The corresponding apparent diffusion coefficients for Sr are (1.33+/-0.13) x 10(-13) m2/s, (1.51+/-0.15) x 10(-13) m2/s, and (1.34+/ 0.10) x 10(-13) m2/s. The Rds obtained from the diffusion experiments for sample densities of 1.8 g/cm3, 2.0 g/cm3 and 2.2 g/cm3 are 1166+/-355, 2113+/-123, 2796+/-171 for Cs, and 713+/-258, 510+/-68, 846+/-158 for Sr. It appears that the retardation factors obtained from the diffusion experiments are about one order of magnitude lower than those derived from the batch experiments. The discrepancy and the possible explanations are discussed in the paper. PMID- 11200883 TI - Moderator-collimator-shielding design for neutron radiography systems using 252Cf. AB - This paper is concerned with the presentation of a study of the general design of an optimized neutron radiography system that utilizes 252Cf. Moderation, collimation and shielding aspects are considered. A Monte Carlo code, MCNP, was used to obtain a maximum and more homogeneous neutron flux in the collimator outlet next to the image plane, taking into account geometric characteristics and an adequate radiation shielding strategy that complies with the radiological protection rules. Among the various moderator materials investigated, the high density polyethylene proved to be the most efficient, with a thermalization factor of 56 cm2. Using a collimator design assembly it was possible to obtain a normalized thermal neutron flux, at the image plane, equals 6 x 10(-6) n cm(-2) s(-1) at an effective collimator ratio of 7.5, or 3.2 x 10(-7) n cm(-2) s(-1) at an effective collimator ratio of 50. The total dose equivalent rates were significantly reduced by the shielding optimization process. PMID- 11200884 TI - Synthesis and biological evaluation of two new radiolabelled estrogens: [125I](E) 3-methoxy-17alpha-iodovinylestra-1,3,5(10),6-tetraen-17beta-ol and. AB - The synthesis of two novel radiolabelled estrogen derivatives, [125I](E)-3 methoxy-17alpha-iodovinylestra-1,3,5(10),6-tetraen-17beta-ol (E[125I]IVDE) and [125I](Z)-3-methoxy-17alpha-iodovinylestra-1,3,5(10),6-tetraen-17beta-ol (Z[125I]IVDE), was carried out aiming to study the influence of the introduction of a C6-C7 double bond on the biological properties of the estradiol molecule. 3 Methoxyestra-1,3,5(10),6-tetraen-17-one was synthesised starting from a suitably protected estrone and subsequently converted into the 17alpha-ethynyl derivative. The radioiodinated derivatives were stereoselectively formed by radioiododestannylation of the corresponding tributylstannyl precursors. The biodistribution of the novel [125I]iodovinylestradiol derivatives was evaluated in immature female mice. Biological data indicated that the Z-isomer, owing to its higher in vivo uptake by the target tissue, has the preferable configuration for further development of similar compounds for estrogen receptor detection. PMID- 11200885 TI - Stabilisation of [131I]meta-iodobenzylguanidine at room temperature as organic extract in ethyl acetate/chloroform. AB - A method of purification of [131I]mIBG (diagnostic dose) by solvent extraction and possibility of its stabilisation by storage in ethyl acetate and chloroform at up to 40 degrees C for not less than 14 days is described. In order to further enhance the utility of this finding, the organic extract was dispensed into vials and dried. Vials containing such dried residue of [131I]mIBG stored at up to 40 degrees C was also found to be stable for at least 10 days. The final product reconstituted as aqueous solution resulted in 90% recovery with 99% radiochemical purity as assessed by previously reported methods, as well as a relatively more rapid paper chromatography method standardised by us. These interesting findings promise simpler and economic packaging besides transport of diagnostic doses of [131I]mIBG. PMID- 11200886 TI - Decay of 72Ga. AB - The gamma-ray spectrum of 72Ge following the beta- decay of 72Ga has been studied using both single and gamma-gamma coincidence spectroscopy techniques. The energies and intensities of 110 gamma-rays have been determined, 26 of them were observed for the first time and 20 have been confirmed. Of the total number of gamma-rays observed, 95 have been placed in a proposed level scheme containing 31 levels. This includes five new levels at 2303, 2694, 3067, 3097 and 3420 keV. PMID- 11200887 TI - Study of nuclear quadrupole interactions in different environments of decaying atoms of 75Se by sum peak method. AB - The sum peak intensity I400 (279 + 121 keV) relative to its singles peak intensity I279 or I121 has been determined in various environments of 75Se by gamma-gamma summing technique in a single HPGe detector. The change in intensity has been used to determine nuclear quadrupole interaction frequencies and electric field gradient components in different environments, e.g. Se-glycerol, Se-hydrochloric acid (HCl), Se-perchloric acid (HClO4), Se-blood samples with and without anti-coagulant, Se-alanine and Se-cysteine at different pH values. The electric field gradient is found to vary with chemical complex formation. PMID- 11200889 TI - Simultaneous determination of 226Ra and 210Pb in groundwater and soil samples by using the liquid scintillation counter-suspension gel method. AB - A method for the simultaneous determination of 226Ra and 210Pb in groundwater and soil samples by liquid scintillation counting was developed. Radium and lead were separated together from the samples as Ba(Ra) x PbSO4 co-precipitate, which was centrifuged and dissolved with 0.1 M EDTA solution (pH 9.0). Radium was separated as Ba(Ra)SO4 co-precipitate by adding ammonium sulfate and adjusting the pH of the solution to 4.2. Lead remaining in the solution was separated as PbSO4 precipitate by adding 9 M sulfuric acid. These Ba(Ra)SO4 and PbSO4 precipitates were purified with EDTA solution and used for measurement. To save time and to make counting samples simpler, direct counting of Ba(Ra)SO4 and PbSO4 precipitates instead of the phosphoric acid fusion method was attempted. Ba(Ra)SO4 and PbSO4 precipitates were suspended in the scintillation gel, and measured. Two liquid scintillation cocktails, Instagel XF and UltimaGold AB were used to prepare the counting samples. A mixture of water (40%), Instagel XF (40%) and UltimaGold AB (20%) formed a stable gel. Activities of 226Ra and 210Pb were calculated from the alpha spectrum of Ba(Ra)SO4 and beta spectrum of PbSO4, respectively. The long-term stability of the suspension gel was good. The analytical results of 226Ra and 210Pb in spiked groundwater samples were in good agreement with the known concentrations of 226Ra and 210Pb. The analytical values of 226Ra and 210Pb in the soil reference samples were within 11.5 and 1.6% of the relative error from the reference values, respectively. PMID- 11200888 TI - ESR dosimetry of 89Sr and 153Sm in bone. AB - The radiation absorbed dose in the rabbit bone delivered by 153Sm-EDTMP (samarium ethylenediaminetetra methylene diphosphonic acid) and 89SRCl2 (strontium chloride) was measured by means of electron spin resonance (ESR). These radioisotopes are used in systemic radiotherapy for palliation of painful bone metastases. The knowledge of the dose is important in order to avoid side effects to the bone marrow. The ESR radiation dose signal was calibrated by the additive dose method using cobalt-60 gamma rays. For 153Sm-EDTMP, the bone doses in three rabbits were (4 +/- 2), (5 +/- 1) and (5 +/- 2) cGy kg/MBq. For 89SrCl2, a dose of (2 +/- 1) cGy kg/MBq was found in one rabbit. PMID- 11200890 TI - Systematics for the cross-sections of the reactions (n, p), (n, alpha) and (n, 2n) at 14.5 MeV neutrons. AB - Systematics are proposed for the (n, p), (n, alpha) and (n, 2n) reactions cross sections at 14.5 MeV neutron energy based on the statistical model, with consideration of the Q-value dependence and odd-even effects. The obtained relations are compared with other recently proposed systematics based on the statistical model as well as on the asymmetry parameter dependence. PMID- 11200892 TI - Simultaneous measurement of 89Sr and 90Sr in aqueous samples by liquid scintillation counting using the spectrum unfolding method. AB - Two radiostrontium isotopes, 89Sr and 90Sr, were measured simultaneously by liquid scintillation counter coupling with a full spectrum DPM counting protocol. Strontium was separated from the aqueous media by extraction chromatography using Sr-spec resin. Individual count rates were evaluated from quench correlation curves for 89Sr and 90Sr related with SIS and tSIE quench indicators. The method exhibited a counting efficiency of 95% for 89Sr and 92% for 90Sr within their full energy channels and gave highly precise results when the sample was counted within 4 h after strontium separation. Lower limits of detection were 37 mBq/l for 90Sr and 32 mBq/l for 89Sr with a 60 min counting time. PMID- 11200891 TI - A study of radon and thoron release from Egyptian building materials using polymeric nuclear track detectors. AB - The free exhalation rates of both thoron and radon, the specific activities of 224Ra, and 226Ra, and the physical properties, such as the emanation coefficients and radon effective diffusion coefficient of several building material samples were determined using LR-115 and CR-39 polymeric nuclear track detectors. The free areal exhalation rate was measured by the sealed cup-technique, whereas the radium content was obtained by the alpha-autoradiographic method. The calibration coefficient for thoron measurements in air using cylindrical cup equipped with LR 115 detector was estimated. Moreover, the calibration coefficients for measurements of the specific activities of 224Ra and 226Ra were also evaluated. New method was developed for evaluating the emanation coefficient as well as the diffusion coefficient of radon isotopes in the studied materials. PMID- 11200893 TI - Measurements and calculations of neutron spectra modified by iron slabs bombarded by neutrons with energies up to 14 MeV. AB - Neutron spectra behind iron slabs of different thicknesses have been measured in the energy range from 1.6 to 14 MeV using a proton recoil spectrometer and 2H(d, n)3He and 9Be(d, n)10B neutron sources. The measured results have been compared with the predicted ones using the three dimensional Monte Carlo code MCNP 4A and pointwise cross sections from the ENDF/B-IV and ENDF/B-VI data files. The results show that the ENDF/B-IV calculations are in better agreement with the experiment than those obtained by using the ENDF/B-VI cross section data. PMID- 11200894 TI - Calculations for the excitation functions of 3-26 MeV proton reactions on 66Zn, 67Zn and 68Zn. AB - Calculation of excitation functions of 66Zn(p,n)66Ga, 66Zn(p,n + p)65Zn, 66Zn(p,2n)65Ga, 67Zn(p,2n)66Ga, 68Zn(p,n)68Ga, 68Zn(p,2n)67Ga natZn(p,xn)66Ga and natZn(p,xn)67Ga reactions has been carried out using the statistical and pre equilibrium nuclear reaction models in the 3-26 MeV energy range. The calculational results are compared with the reported measurements and evaluations. PMID- 11200895 TI - Normalisation with coherent scatter signal: improvements in the calibration procedure of the 57Co-based in vivo XRF bone-Pb measurement. AB - The feasibility of a normalised calibration variable to account for interpatient variability for in vivo 57Co XRF (X-ray fluorescence) finger bone-lead measurements was assessed. Normalising the lead X-ray intensities to the coherent scatter signal was investigated by experiment and Monte Carlo simulation. The X ray to coherent ratios for a fixed lead concentration were within 5-10% of the mean, within uncertainty, over a physiologically relevant range of finger bone sizes and overlying tissue thicknesses. This is an acceptable level of variation to introduce, as it is less than the uncertainty of a typical in vivo measurement. Normalisation has several advantages compared with the current method of correcting for interpatient variation, as it eliminates the need for transporting extensive equipment to on-site measurements, reduces the subject dose by a factor of two, and increases the objectivity of the bone-Pb assessment. PMID- 11200896 TI - Geological influence on terrestrial gamma radiation dose rate in the Malaysian State of Johore. AB - Measurements of environmental terrestrial gamma radiation dose-rate (TGRD) have been made in Johore, Malaysia. The focus is on determining a relationship between geological type and TGRD levels. Data were compared using the one way analysis of variance (ANOVA), in some instances revealing significant differences between TGRD measurements and the underlying geological structure. PMID- 11200897 TI - The application of prompt-gamma neutron activation analysis to borehole logging for coal. AB - The PGNAA technique was tested for the in-situ determination of ash, Fe, Si, Al and density of coal seams in water-filled boreholes. The technique is also able to determine in situ the deformation temperature of coals for which a correlation exists between the deformation temperature and the percentage of Al, Si and Fe present in coal. The logging tool employed a 2.5 microg 252Cf neutron source. PMID- 11200898 TI - Atmospheric interactions at northern high latitudes from weekly Be-isotopes in surface air. AB - We present weekly 7Be (from 1972 to 1995), and weekly/seasonal 10Be (for 1994) data in surface air from ground level stations in Sweden with a coverage of most of the northern high latitudes (56 degrees-68 degrees N). Our Be data are regionally representative and reveal seasonal variation and coupling with tropospheric air mass from middle-low latitudes. The Be data also suggests a few percent, and sometimes episodic, incursion of stratospheric air mass. Frequent precipitation depletes the Be isotopes in the air, but cyclone events contribute to enrichments. A strong coherence between the 7Be record and short-term (monthly seasonal) change in solar activity is observed which introduces a new mechanism for driving the amplitude of seasonal variation. PMID- 11200899 TI - A probabilistic description of radioactive contamination: a multivariate model. AB - A multivariate discrete probability model is used to facilitate the description of gamma-ray spectroscopic data obtained from radioactively contaminated territory, east of the former Semipalatinsk nuclear test site in Kazakhstan. Two possible estimators of probabilities of interest have been considered: maximum likelihood and unbiased estimators. We show that unbiased estimators are much easier to compute. The model was used in two variants: (i) several radionuclides in spatially independent measurements, (ii) a single radionuclide in spatially dependent measurements. We show that, in both cases, it is important to take into account the correlation for the accurate evaluation of probabilities of interest. PMID- 11200900 TI - Natural radioactivity and gamma dose from Sri Lankan clay bricks used in building construction. AB - The specific radioactivity concentrations of 226Ra, 232Th and 40K have been determined by gamma ray spectrometry with an HPGe detector in clay brick samples from kiln sites located in 17 towns. The average values of the measured activities are 35, 72, and 585 Bq kg(-1), respectively, for the above radionuclides. The average estimated radium equivalent concentration is 183 Bq kg(-1) and is comparable with reported values for many countries in the world. This value and the value obtained from the criteria formula suggest that the use of local clay bricks do not pose a radiological hazard. The calculated average absorbed dose rate in air within buildings was found to be 102 nGy h(-1) while the population weighted indoor annual effective dose was 0.20 mSv. PMID- 11200901 TI - Cerebral malaria. AB - Cerebral malaria is a rapidly progressive potentially fatal complication of Plasmodium falciparum infection. It is characterized by unarousable and persistent coma along with symmetrical motor signs. Children, pregnant women and non-immune adults are more susceptible to have cerebral malaria. Several clinical, histopathological and laboratory studies have suggested that cytoadherence of parasitized erythrocytes (mechanical hypothesis), and neuronal injury by malarial toxin and excessive cytokine (e.g. tissue necrosis factor alpha) production (cytotoxic hypothesis) are possible pathogenic mechanisms. Several associated systemic complications like hypoglycemia, hypovolemia, hyperpyrexia, renal failure, bleeding disorders, anemia, lactic acidosis and pulmonary oedema may contribute in the pathogenesis of coma, and are responsible for high mortality. The meticulous supportive care along with intravenous administration of antimalarial drugs are corner-stone of the treatment. Quinine is currently, drug of choice. Artimisinin derivatives are equally effective and can be used by intramuscular route. In severe cases exchange blood transfusion may be an effective alternative. Corticosteroids has no place in the management of cerebral malaria. The occurrence of convulsions are common in children, these can be prevented with the use of single intramuscular administration of phenobarbitone. Despite advances in the management mortality and morbidity have not changed much. A large number of surviving patients are left with permanent neurological sequelae. There is a need to search for effective malaria prevention and interventional strategies to avert high mortality and morbidity associated with cerebral malaria. PMID- 11200902 TI - Cryptococcal prostatitis in a patient with chronic lymphocytic leukemia. AB - Cryptococcosis is a systemic mycosis usually affecting patients of immunodeficiency i.e. transplants recipients, patients on chemotherapy for neoplastic diseases and in those suffering from human immunodeficiency virus infection. We report a 52-year old male suffering from chronic lymphocytic leukemia (CLL) on chemotherapy who presented with fever and features of prostatism. Cryptococcus neoformans infection (CN) was diagnosed on aspiration of a prostatic nodule. Subsequent investigations revealed a disseminated involvement by cryptococcus. The case represents an unusual presentation of disseminated cryptococcosis. PMID- 11200903 TI - Strongyloides hyperinfection syndrome--an unappreciated opportunistic infection. AB - A case of respiratory hyperinfection syndrome which occurred in a patient on long term corticosteroid therapy is reported here for it's rarity. Intestinal infection with this parasite should be looked for and treated before the initiation of immunosuppressive therapy. PMID- 11200904 TI - Non familial juvenile polyposis presenting as chronic intestinal obstruction. AB - Juvenile polyps are the commonest colonic polyps seen in children and present most often with rectal bleed. Intussusception is an extremely rare presentation in juvenile polyposis (JP) syndrome. This case highlights the rare association of ileo-colic intussusception with non-familial Juvenile Polyposis. PMID- 11200905 TI - Trichosporon beigelii peritonitis in a HIV-positive patient on continuous ambulatory peritoneal dialysis. AB - Peritonitis, the commonest complication of peritoneal dialysis, is usually bacterial in origin. Fungal peritonitis is rarely encountered. We are reporting a rare case of fungal peritonitis caused by Trichosporon beigelii in a patient on continuous ambulatory peritoned dialysis (CAPD), who was HIV positive. PMID- 11200906 TI - Poems syndrome. PMID- 11200907 TI - Renal stone disease as extra skeletal manifestation of osteogenesis imperfecta. PMID- 11200908 TI - Masked myotonia presenting as recurrent head injury. PMID- 11200910 TI - Controversies about the statistical significance level. PMID- 11200909 TI - Interesting case of migraine presenting with recurrent episodes of migraine coma. PMID- 11200911 TI - Human leptin deficiency and resistance. PMID- 11200912 TI - Increased sacral angle and chronic low backache. PMID- 11200913 TI - Elections and nail growth: a new physical sign? PMID- 11200914 TI - Paroxysmal alien hand syndrome. PMID- 11200915 TI - Changing trends of poisoning at railway stations. PMID- 11200916 TI - Role of oxygen free radicals in septic shock. PMID- 11200917 TI - Role of oxygen free radicals in shock. AB - AIMS OF THE STUDY: To study lipid peroxidation, magnesium levels (Mg) in plasma and red cells (RBC), superoxide dismutase (SOD) and catalase (CAT) activities in the plasma and RBC of shock patients. METHODOLOGY: Twenty five patients with clinically defined septic shock and 30 healthy volunteers were selected for the study to study the parameters of oxidative stress. RESULTS: Septic shock patients had higher activities of plasma and RBC SOD and CAT activities as compared to control. Also, plasma Mg and malonaldehyde (MDA) levels were higher in shock patients as compared to controls. While, RBC Mg levels were similar in two groups. CONCLUSIONS: The finding of increased concentration of MDA, Mg, SOD and CAT in sepsis implicates oxygen free radicals in the pathophysiology and free radical scavengers may have a role in organ preservation. PMID- 11200918 TI - Role of supravital staining of urine sediment and bright field microscopy in diagnosis of acute renal failure in bedside medicine. AB - BACKGROUND: An early accurate etiological categorization of acute renal failure (ARF) into acute glomerulonephritis (AGN), acute tubular necrosis (ATN) and acute interstitial nephritis (AIN) is very important in clinical medicine. METHODS: To evaluate the efficacy of a simple, cheap supravital staining method developed in our laboratory, we examined urine of 32 cases of ARF at their initial presentation in oliguric phase, which were later biopsied. The stain consisted of 1% crystal violet and 0.5% safranin in normal saline. The coverslip preparations of coded and stained urine sediments were examined under ordinary bright field microscope (BFM) by two independent observers. RESULTS: The renal biopsy showed 12 cases of AGN, 12 ATN and 8 AIN. The diagnosis could be predicted by supravital staining method in 75% cases with 95% uniformity among two observers with a sensitivity of 85.7% for AGN followed by AIN (80%) and ATN (75%). CONCLUSION: Thus this simple supravital staining technique can be used with ordinary BFM for accurate urine sediment analysis in cases of ARF in bedside medicine. PMID- 11200919 TI - Ventilatory pulmonary function tests in type 1 diabetes mellitus. AB - OBJECTIVE: To study the ventilatory pulmonary function tests (VPFT) in type one diabetes mellitus and to correlate it with duration, meticulous metabolic control and various complications of diabetes. METHODOLOGY: Spirometric evaluation of 50 young (15-30 years of age) type one diabetes mellitus patients was done under the case control longitudinal study. After recording baseline parameters patients were subjected to PFT. OBSERVATIONS: Degree of derangement in VPFTs was directly related to duration and metabolic control of diabetes. VPFT parameters such as FVC, FEV1, PEFR, MEF 75% and MEF 25% showed significant reduction (p = 0.009, = 0.001, = 0.001, = 0.05 respectively). Similarly patients with HbA1c > 10% showed significant reduction in FVC, FEV1, PEFR and MEF 75% (p = 0.001 for each). Diabetic patients with complications particularly peripheral neuropathy and nephropathy had significant reduction in FVC, FEV1 and PEFR (p = 0.001). CONCLUSION: Spirometric evaluation in type one diabetes mellitus showed varying derangements in the different parameters of VPFTs, suggestive of dominantly restrictive with some obstructive pattern as indicated by significant decline in FVC, PEFR and MEF 75%. PMID- 11200920 TI - Behavioural intervention in the management of compliance in young type-I diabetics. AB - OBJECTIVES: a) To examine the efficacy of a behavioural intervention programme in the management of compliance in young Type I diabetics, b) To examine the efficacy of a behavioural management programme in enhancing metabolic control in young Type I diabetics, c) To examine the effect of behavioural intervention on level of diabetes knowledge and quality of life in young Type I diabetics. METHODS: A total of 40 patients (Experimental group n = 20, Control group n = 20) was selected from local hospitals' pediatric, endocrinology and diabetology units. The experimental group received 15 individual sessions of behavioural intervention, consisting of behavioural counseling for family and significant others, relaxation, diabetes education and specific behavioural and cognitive strategies such as reinforcement, target-setting and cognitive restructuring. Assessment was carried out on various psychological measures as well as the glycosylated hemoglobin test (HbA1), at pre and post treatment periods. RESULTS: The scores of the two groups were compared at post treatment point. Results indicate that there was significant improvement in the experimental group in compliance and metabolic control. There were also significant changes noted in the level of diabetes knowledge as well as the reported quality of life. These changes in compliance and metabolic control were maintained at a three month follow-up period. CONCLUSIONS: Behavioural intervention can be included as an effective adjunct to routine medical care in the management of young Type I diabetics, especially in the management of compliance and metabolic control, enhancement of knowledge and quality of life. PMID- 11200921 TI - Aetiology and treatment response in patients with spontaneous diabetes insipidus. AB - BACKGROUND: Spontaneous diabetes insipidus (DI) is an uncommon disorder. This study analysed aetiology and response to treatment in patients with spontaneous DI admitted to the endocrinology service of a teaching hospital. METHODS: Twenty patients were seen over a eight year period (1991-1998). The diagnosis of DI was confirmed in each case by the standard water deprivation test. Appropriate diagnostic procedures were carried out to determine aetiology. RESULTS: Sixteen patients had complete DI and four patients had partial DI. Eighteen had central DI and two nephrogenic DI. The etiology in sixteen of the eighteen patients with central DI included: histiocytosis--three, eosinophilic granuloma--two, neurosarcoidosis--three, viper-bite--one, head injury--two, germinoma--one, post RT--one, tuberculous meningitis--one, acute-sphenoid sinusitis--one and hypothalamic tumour--one. Eleven patients (61%) responded to tab. carbamazepine, while nine (45%) required intra-nasal DDAVP. One of the two patients with nephrogenic DI responded to thiazide diuretic. CONCLUSION: We identified the aetiology in 88% of our patients with central DI. Histiocytosis and sarcoidosis accounted for 40%. Most patients (61%) responded to treatment with oral carbamazepine, others required intra-nasal DDAVP. PMID- 11200922 TI - Lung function in mitral stenosis. AB - OBJECTIVES: The aim of this study was to look to for a relationship between pulmonary artery pressure (PAP), left atrial pressure (LAP), mitral valve area (MVA) and transmitral gradient (Gr) on the one hand and the spirometric data on the other, in cases of mitral stenosis. METHODS: The spirometry values measured were forced vital capacity (FVC), forced expiratory volume in one second and as percent of FVC (FEV1, FEV1/FVC%), forced expiratory flow between 25% to 75% of FVC (FEF 25-75%), at 50% of FVC (FEF 50%) 75% of FVC (FEF 75%) and peak expiratory flow rate (PEFR). The PAP, LAP, MVA and Gr were measured at echocardiography and cardiac catheterisation. RESULTS: Analysis of results was done of 60 patients in four groups divided on basis of mean PAP: Group 1 with least and group 4 with highest mean PAP. FVC values were reduced in direct proportion to PAP, LAP, MVA and Gr in three out of four groups. FEV1% as a percent of predicted value showed uniform reduction in all the groups, PEFR was moderately affected in group 1 and most severely in group 4. Values of FEV1/FVC% were within normal range in all the groups. FEF 25-75%, and FEF 50% showed serial reduction in values in keeping with the elevation of the PAP. FEF 75% was also moderately affected in group 1 and most severely in group 4. CONCLUSION: We found that a moderate restrictive defect and a small airway defect which is found in cases of mitral stenosis, directly correlates to the PAP, LAP, MVA and Gr. There was no significant involvement of the larger airways. PMID- 11200923 TI - Evaluation of oxidative stress before and after haemodialysis in chronic renal failure. AB - OBJECTIVE: To evaluate the oxidative stress before and after haemodialysis in chronic renal failure patients. METHODS: A prospective study comprising of 22 patients of CRF who have to receive their first haemodialysis. All patients were subjected to standard four hours haemodialysis. The parameters of oxidative stress i.e. erythrocyte malonaldehyde (MDA), reduced glutathione (GSH) and superoxide dismutase (SOD) were measured before and after haemodialysis. RESULTS: The value of mean erythrocyte MDA (9.40 +/- 3.36 mumol/L) and SOD (617 +/- 64.33 units/ml) were significantly higher in patients of CRF before haemodialysis than in controls (p < 0.001). The mean GSH levels were significantly lower (451 +/- 63.91 micrograms/ml) in patients than in controls before haemodialysis (p < 0.001). After haemodialysis MDA levels further increased (12.27 +/- 4.38 mumol/L), SOD levels decreased (458 +/- 69.58 EU/ml) and GSH levels further decreased (396 +/- 41.41 micrograms/ml) (p < 0.001). CONCLUSIONS: There was an evidence of oxidative stress in patients of CRF before haemodialysis which increased further after haemodialysis, the mechanisms of which is not delineated. The procedural factors may be contributing in the increased oxidative stress after haemodialysis. PMID- 11200924 TI - Comparative bioavailability study of clonazepam after oral administration of two tablet formulations. AB - OBJECTIVE: To assess the bioavailability of clonazepam from two brands of 2 mg tablet formulations--Epitril and reference brand. METHODS: A two-way randomised cross-over bioavailability study was carried out in 12 healthy male volunteers. Coded plasma samples were analysed for levels of clonazepam by high performance liquid chromatography (HPLC) method. RESULTS: The mean Cmax, Tmax t1/2 beta and AUC (0-48) for Epitril were: 16.31 +/- 3.07 ng/mL, 1.63 +/- 0.48 h, 46.97 +/- 12.26 h and 207.70 +/- 57.07 ng/ml.h; for reference brand were 19.75 +/- 5.95 ng/mL, 1.42 +/- 0.29 h, 46.88 +/- 11.29 h and 215.70 +/- 50.89 ng/ml.h respectively. These were comparable and the differences were not statistically significant. CONCLUSION: Based on above pharmacokinetic parameters, Epitril was bioequivalent to reference brand. PMID- 11200925 TI - Non traumatic paraparesis: aetiological, clinical and radiological profile. AB - AIM OF STUDY: To study the aetiological and clinical profile of non traumatic paraparesis and radiological correlation with newer aids of diagnosis like CT scan, MRI. METHODOLOGY: Forty cases of non traumatic paraparesis admitted at Sri Sayaji General Hospital, Baroda were studied. The clinical, laboratory data and radiological features were analyzed. RESULTS: Spinal tuberculosis was commonest cause (30%) of paraparesis followed by acute transverse myelitis (20%) and then by primary spinal cord tumours (10%). Incidence of paraparesis was highest (32.5%) in third decade. Backache (75%), parasthesias (62.5%) were common symptoms accompanying paraparesis. Spasticity was present in 57.5% patients. Myelography showed block in 58.5% patients. CT scan following myelography exactly delineated the primary spinal cord tumours and confirmed diagnosis in spinal TB, arachnoid cysts and other compressive myelopathies. MRI, showed plaques of demyelination in two patients, and epidermoid cyst in one patient. CONCLUSION: Tuberculosis of the spine was the commonest cause of paraparesis followed by acute transverse myelitis. CT scan and MRI are important diagnostic aids in patients of paraparesis. PMID- 11200926 TI - Pictorial CME. PMID- 11200927 TI - Role of micro-nutrients and trace elements in carcinoma of larynx. AB - Cancer of the larynx is fourteenth most common cancer in the world. Evidence from case-control studies conducted in developed as well as developing countries suggest that specific micro-nutrients and trace elements have been implicated to be significantly associated with laryngeal carcinoma. The association of these micro-nutrients and trace elements with laryngeal cancer has been discussed in this review article. PMID- 11200928 TI - Stevens-Johnson syndrome and toxic epidermal necrolysis-challenges of recognition and management. AB - Skin adverse drug reactions (ADRs) generally present as transient erythematous macular/papular rashes. However these can many a times be the initial presentation of serious muco-cutaneous ADRs such as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). The incidence of SJS varies from 1.2 to 6 per million patient-years and that of TEN to be 0.4 to 1.2 per million patient-years. The pathophysiological mechanism of SJS and TEN have not been fully elucidated. The aetiological factors of SJS and TEN are diverse; drugs being the cause in more than 80% cases of TEN and about 40-50% cases of SJS. Mucous membranes are affected in nearly all cases. The extent of epidermal sloughing may vary and forms a basis for the classification of an individual case as SJS or TEN. Prognosis of SJS is better than that of TEN; mortality rates being about 5% and 30%-40% respectively. Specific therapy for these conditions is yet not available. The use of systemic corticosteroids has been controversial. Early diagnoses can prevent/reduce the morbidity of such serious ADRs. This article provides a brief review of the clinical presentation and management of SJS and TEN. PMID- 11200929 TI - Clinical implications of insulin-like growth factors and their binding proteins in reproduction. PMID- 11200930 TI - Effect of calcimimetic agent, KRN568, on gastrin secretion in healthy subjects. AB - KRN568 is a calcimimetic compound which acts on the calcium sensing receptors (CaR) on the parathyroid gland to suppress secretion of PTH. A recent report has demonstrated that CaRs are expressed on cultured human antral gastrin cells and that gastrin secretion is stimulated by an increase in extracellular calcium level. However, the effect of KRN568 on serum gastrin levels has yet to be clinically assessed. We therefore studied the effect of this calcimimetic on gastrin secretion in healthy subjects enrolled in the phase 1 study for KRN568 currently carried out in Japan. Single doses of KRN568, ranging from 25 mg to 400 mg, were orally administered to 6 healthy male volunteers at fasting and after meal. One subject proved to be a poor metabolizer (PM) for this compound and showed more than 10-fold high concentrations of plasma KRN568 (fasting Cmax 90.8 and non-fasting 83.8 ng/ml) compared to the other 5 individuals (Cmax 6.5 +/- 2.2 and 7.4+/- 1.6 ng/ml, respectively). Plasma gastrin levels showed mild but apparent increase (from 30 to 125 pg/ml) in this particular subject, while there were no significant increases in the other five people (from 34 +/- 6 to 63 +/- 3 pg/ml) after oral administration of 400 mg KRN568 at fasting. In the PM, administration of KRN568 resulted in extraordinarily high serum drug levels associated with transient increase of gastrin levels. This observation suggested that calcium-induced stimulation of gastrin secretion in human was mediated by a mechanism involving CaR. Potential side effects related to the increased gastrin secretion may be warranted in the practical use of this compound. PMID- 11200931 TI - Major determinants of the carotid intima-media thickness in type 2 diabetic patients: age and body mass index. AB - The present study has been designed to quantify and compare right and left carotid intima-media thicknesses (IMT) in type 2 diabetics and healthy controls. It was also intended to investigate the effects of various risk factors on the carotid IMT in these subjects. A total of 122 subjects; 70 patients with type 2 diabetes and 52 non-diabetic subjects as controls, were recruited for the study. Right and left common carotid artery stiffness indices were assessed with ultrasonography in both groups. Age, body mass index (BMI), duration of diabetes, cigarette smoking, lipid profile including lipoprotein a, Chlamydia pneumonia seropositivity, glycemic indices, fasting insulin levels, serum fibrinogen levels and presence of hypertension, coronary artery disease, degenerative complications of diabetes mellitus were all assessed in order to define their role as determinants of carotid artery IMT. The difference between the groups regarding mean carotid IMT was statistically significant for the left carotid arteries (p = 0.028) and borderline significance was found for the right carotid arteries (p = 0.055). Age has a very strong association with carotid IMT in diabetic patients (p < 0.0001) with univariate analysis. According to the results of multivariate analysis, age and BMI were found to be the most important independent determinants of carotid IMT for both sides. When age was excluded from the model, BMI and coronary artery disease were found to have strong association with IMT on the right (p = 0.0036 and 0.0249) and BMI was the only significant determinant for the left side (p = 0.0025). This study shows that carotid IMT is greater in diabetic subjects compared with healthy controls. For the diabetic subjects, age, BMI and presence of coronary heart disease have a strong influence on the atherosclerotic process of the carotid arteries. PMID- 11200932 TI - Evaluation of factors during OGTT to correlate insulin resistance in non-diabetic subjects. AB - The correlation between various factors obtained during oral glucose tolerance tests (OGTT) and insulin sensitivity tests (steady state plasma glucose, SSPG method) were analyzed in non-diabetic subjects by Pearson's simple correlation. Similar data were obtained for normal as well as normal and impaired glucose tolerance (IGT) subjects. Three factors (AUCI(120)0AUCG(120)0, AUCI(120)0 and AUCI(120)60, area of under curve (AUC), insulin (I), glucose (G)) were found to have significant correlation (r=0.47-0.54) with SSPG, thus indicating insulin resistance. Those with hyperinsulinemia were noted to have insulin resistance with high precision (98%), but insulin resistant subjects without hyperinsulinemia were all judged to have normal sensitivity. These three factors all had high specificity (98%), but low sensitivity (21-25%) with false negative results being obtained in 75-78%, and false positive results in less than 2%. It was difficult to distinguish positive and negative for the insulin resistance by receiver operating characteristic (ROC) curve of I0G0. The sensitivity of which was 12.8% and specificity 93.8%. By ROC curve, the specificities and sensitivities for the proposed factors, including homeostatic model assessment (HOMA) product (I0G0, I0-120, G0-120, insulin and glucose at 0-120' during OGTT) ranged from 60 to 70%, which is far from an acceptable level of 90% or more. Therefore, these factors were useful to correlate insulin sensitivity with OGTT results in hyperinsulinemic subjects or in general non-diabetic subjects, but less useful when it came to identifying individual cases with insulin resistance. These parameters should be used only in non-diabetic subjects and their significance is thought to be restricted to cases with hyperinsulinemia. PMID- 11200933 TI - Alternate exon in the 5'-untranslated region of the human ACTH receptor gene. AB - The human ACTH receptor (ACTH-R) gene consists of two exons; the first encodes the 5'-untranslated region (UTR) and the second encodes part of the 5'-UTR, the entire coding region, and the whole of the 3'-UTR. While investigating the transcription initiation site of the human ACTH-R gene by 5'-rapid amplification of cDNA ends, we found a 157-bp alternate exon in the 5'-UTR. This newly identified exon was irrelevant to the alternate exon in the mouse ACTH-R gene which we reported previously. PMID- 11200934 TI - Growth hormone secretory dynamics over the menstrual cycle. AB - Whether GH secretion in women varies over the menstrual cycle is uncertain. Previous investigations have led to conflicting conclusions; some studies suggested that there is an estrogen mediated rise in GH during the periovulatory (PO) and luteal (L) phases whereas others indicated no change in GH axis over the cycle. Differences in conclusions could relate to heterogeneity of the study populations, GH sampling paradigms or sensitivity of the GH assays used. In order to investigate whether GH secretion varied over the cycle, 24-h GH profiles using every 10-min sampling were obtained in 6 ovulatory women during the early follicular (EF), PO and L phases of the cycle. The TSH response to TRH, GH response to GRH and fasting plasma IGF-I were measured on each occasion. There was a trend toward higher integrated GH concentration (IGHC) during the PO phase, although this difference was not statistically significant (3284+/-721 vs 4542+/ 872 vs 4071+/-699 microg/min/L; EF vs PO vs L; p=0.09). Similarly, deconvolution estimated GH secretion did not vary over the cycle (p=0.56). There were no differences in GH pulse amplitude or frequency. There were no correlations between IGHC and sex steroids. Serum IGF-I was constant over the cycle (272+/-38 vs 277+/-31 vs 265+/-38 microg/L; p=0.89). The TSH response to TRH and GH response to GRH did not vary over the cycle. We concluded that the effect of changes in the ovarian steroid milieu on the GH axis during spontaneous menstrual cycles is minimal. PMID- 11200935 TI - A clinical feature of hyperlipidemia in patients with central diabetes insipidus. AB - In this study, we analyzed plasma lipid and lipoprotein levels before and after treatment with 1-desamino-8-D-arginine vasopressin (DDAVP) in subjects with partial and complete central diabetes insipidus (DI) in order to determine how a shortage and supplement of this hormone affect plasma lipid metabolism. The subjects consisted of 6 patients with partial and 6 with complete central DI. After treatment with DDAVP through nasal cavity, plasma total cholesterol (TC) level did not decrease either in complete or partial form. Plasma triglyceride (TG) levels decreased from 306+/-175 mg/dl to 198+/-91 (35% decrease, p=0.027) in complete form, while TG did not change significantly in partial form. A detailed investigation of plasma lipoprotein metabolism during treatment with DDAVP was carried out in 3 of the 6 subjects with complete form of DI. Lipoprotein lipase activity and mass in post-heparin plasma from those three subjects tended to increase after treatment with DDAVP, along with the complete disappearance of an unusual lipoprotein between low density lipoprotein (LDL) and very low density lipoprotein (VLDL) as analyzed by polyacrylamide gel electrophoresis. These results suggest that the DDAVP treatment has a favorable effect on lipid and lipoprotein metabolism, especially triglyceride-rich lipoproteins, either directly or through modifying factors contributing to lipid metabolism. PMID- 11200936 TI - Twenty-kilodalton human growth hormone (20K hGH) secretion from growth hormone secreting pituitary adenoma cells in vitro. AB - Circulating human growth hormone (GH) consists of several molecular isoforms. Increased proportion of circulating non-22K hGH and 20K hGH was reported in active acromegaly. In this study, we studied the release of 20K and 22K hGH from cultured GH-producing human pituitary adenoma cells in vitro. Pituitary adenoma cells obtained from 6 acromegalic patients were cultured and submitted to perifusion experiments. Concentrations of 20K and 22K hGH in the serum and the perifusion effluent were determined by specific enzyme-linked immunosorbent assays recently developed. The %20K value varied in a wide range from 3.58 to 8.72% in vitro and was lower than in the serum (mean+/-SD: 6.57+/-1.88% vs 9.08+/ 2.12%, P<0.05). There was no correlation between the %20K values in vitro and in vivo (r=0.31, P>0.05). The in vitro secretions of 20K and 22K hGH were in parallel and strongly correlated (r=0.953, P<0.001). These findings suggest that different GH-producing pituitary adenoma cells secrete 20K hGH in variable amounts and that the proportion of 20K hGH in the serum might be affected by metabolic clearance of hGH isoforms. It was also suggested that 20K and 22K hGH might be secreted in toto from GH-producing human pituitary adenoma cells. PMID- 11200937 TI - Frequency of facial angiofibromas in Japanese patients with multiple endocrine neoplasia type 1. AB - The high frequency of cutaneous manifestations in patients with multiple endocrine neoplasia type 1 (MEN 1) has recently been reported. Since prevalence of some cutaneous diseases varies among different ethnic groups, we examined the frequency of facial angiofibromas in Japanese patients with familial MEN 1. Among 27 patients with germline MEN1 gene mutation and one asymptomatic gene carrier, angiofibromas were identified in 43% (12/28) of the subjects. This frequency was significantly lower than that of Caucasian patients, but nonetheless almost equaled those of pituitary tumors and pancreas endocrine tumors. Angiofibromas should be considered as one of major manifestations in MEN 1 regardless of patients' ethnic origin, and clinicians should pay careful attention to the cutaneous lesions in patients with endocrine tumors. PMID- 11200939 TI - Human chorionic gonadotropin beta-subunit affects the folding and glycosylation of alpha-cys mutants. AB - Human chorionic gonadotropin (hCG) is a member of a family of heterodimeric glycoprotein hormones that contain a common alpha-subunit but differ in their hormone-specific beta-subunits. Both subunits have five and six disulfide bonds, respectively, which consist of cystine knot structure. It is evident from numerous studies that the structure of beta-subunits is rigid, whereas that of alpha-subunit is flexible and can be molded by a beta-subunit. Previously, we reported that secreted forms of a mutants where either cysteine residue in the disulfide bond 7-31 or 59-87 was converted to alanine contained a disulfide linked homodimer in addition to a monomer. To study whether the hCGbeta-subunit affects the conformations of alpha mutants, alpha-subunits lacking either the 7 31 or 59-87 disulfide bond were expressed with wild-type (WT) hCGbeta in Chinese hamster ovary cells, and homodimer formation and glycosylation of dimerized alpha subunit were assessed by continuous labeling with [35S]methionine/cysteine, immunoprecipitation with anti-alpha or -hCGbeta serum, digestion with endoglycosidase-H or -F, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis in a non-reducing condition. Our data showed that a homodimer was not observed in the half-Cys mutants except one, where cysteine at position 7 was converted to alanine, in the presence of beta-subunit. This finding indicated that hCGbeta-subunit rescued the a half-Cys mutants from the formation of intermolecular disulfide-linked homodimer by preferentially combining with the alpha mutants. In both free WT and all mutants treated with endoglycosidase-H, no or faint bands were recognized as the same migration as seen in endoglycosidase-F treatment. Even in the endoglycosidase-H sensitive cases, the amount of sensitive alpha-subunits was less than 5% of total alpha-subunits. In contrast to free alpha-subunits, distinct endoglycosidase-H sensitive bands were seen in both WT and mutants, although the ratio was various. We concluded that hCGbeta-subunit affects the folding and glycosylation of the alpha-subunit mutants. PMID- 11200938 TI - Measurement of anti-thyroglobulin and anti-thyroid peroxidase antibodies using highly sensitive radioimmunoassay: an effective method for detecting asymptomatic focal lymphocytic thyroiditis in the elderly. AB - Subclinical thyroiditis or thyroid dysfunction is relatively common in the elderly. To estimate the effectiveness of measurement of serum levels of anti thyroglobulin and anti-microsomal or thyroid peroxidase antibodies for detecting focal lymphocytic thyroiditis (FLT) in the elderly, we examined the relationships between antibody titer and postmortem histological finding of the thyroid gland in 180 consecutive autopsies (69 women and 111 men) over 60 years of age without any overt clinical thyroid or collagen diseases. FLT was found in 25 cases (13.9%) with female predominance (21.7% in female vs. 9.0% in male). Measurements of serum levels of anti-thyroglobulin and anti-thyroid peroxidase antibodies by radioimmunoassay (TgAb and TPOAb, respectively) were compared with the measurements of anti-thyroglobulin and anti-microsomal antibodies by a hemagglutination technique (TGHA and MCHA, respectively), using sera from 25 patients with FLT and age- and sex-matched 51 patients without FLT. Among 25 cases with FLT, TgAb and TPOAb were positive in 17 (68%) and 12 (48%), respectively. There was a close relationship between degree of FLT and serum level of TgAb or TPOAb (P<0.0001). On the other hand, TGHA and MCHA were positive only in 8 (32%) and 10 (40%), respectively. TgAb and TPOAb were more sensitive than TGHA (68% vs. 32%, P<0.05) and MCHA (48% vs. 40%) to detect FLT. Positive findings in either TgAb or TPOAb significantly improved sensitivity (76%) compared with that of TGHA or MCHA (44%) (P<0.05). Specificities of combined measurements of TgAb and TPOAb (90%) were not significantly different from those of TGHA and MCHA (100%). These findings indicate that TgAb is a more sensitive method for detecting FLT and that its diagnostic sensitivity for FLT increases by using it in combination with TPOAb. Therefore, in the elderly without clinically or biochemically overt thyroid dysfunction, positive TgAb and/or TPOAb could imply presence of FLT, and their titers might reflect degree of inflammation. PMID- 11200940 TI - Self-examination of thyroid nodules. AB - The management of occult small thyroid nodules found by ultrasonography is sometimes problematic. Self-palpation may be utilized in the follow-up of these nodules. We developed a method of thyroid self-examination (TSE). We examined the size of the nodules palpable by this method by ultrasonography. In 78 patients examined, all 38 tumors more than 2 cm in size, whereas only one of 14 tumors less than or equal to 1 cm in size, were palpable. These results suggest the clinical usefulness of TSE in the follow-up of thyroid tumors, which are very common and slow-growing. PMID- 11200941 TI - Substitution of M398T in the second transmembrane helix of the LH receptor in a patient with familial male-limited precocious puberty. AB - Familial male-limited precocious puberty (MPP) is described in a 10 year old patient with typical symptoms of the disease. Sequence analysis of genomic DNA clearly demonstrated a heterozygous T1193C transition in exon 11 of the LH receptor (LHR) gene, which results in M398T substitution in the second transmembrane helix of the protein product of this gene. The same mutation was found in the patient's mother and in her brother. The grandmother and the relatives of the patient's father were free of the mutation. The boy was successfully treated with inhibitors of steroid biosynthesis and androgen antagonists. It is suggested that this mutation caused constitutive activation of the LHR, which results in excessive formation of androgens in Leydig cells and is responsible for the symptoms of precocious puberty in this patient. This is the second case of the familial form of MPP that was maternally inherited. PMID- 11200942 TI - Postnatal development of NADPH-diaphorase activity in the rat: the role of nitric oxide in the ontogeny of arginine vasopression and oxytocin. AB - To clarify the role of nitric oxide (NO) in the ontogeny of arginine vasopressin (AVP) and oxytocin (OXT) neurons in the hypothalamo-neurohypophysial system (HNS), we observed the coexpression pattern of NADPH-diaphorase (NADPH-d) activity and AVP- or OXT-immunoreactivity (IR) in the rat hypothalamus and posterior pituitary during the postnatal period. The enzymatic activity of NADPH d was observed in the supraoptic nucleus (SON), paraventricular nucleus (PVN), median eminence (ME) and posterior pituitary throughout the postnatal development. AVP-containing neurons were clearly observed from postnatal day 1 in both the SON and PVN, while OXT-containing neurons were recognized from postnatal day 14. The coexistence of NADPH-d and AVP or OXT was detected in the SON from postnatal day 14. At postnatal day 21, the coexpression pattern was approximately the same as that of the SON and PVN in adult rats. Our findings indicated that the expression of NADPH-d and OXT was observed from almost the same postnatal period in both the SON and PVN. In addition, the pattern of increased numbers of NADPH-d positive fibers was similar to that of OXT-immunoreactive fibers in both the inner layer of the ME and the posterior pituitary. A good correlation was thus obtained between OXT expression and NADPH-d activity in the HNS during postnatal development. The present study suggests that NO is more closely involved in the expression and regulation of secretion of OXT than AVP. PMID- 11200943 TI - Gender-related difference in relationship between insulin resistance and serum leptin level in Japanese type 2 diabetic and non-diabetic subjects. AB - It remains controversial whether or not a correlation exists between serum leptin levels and insulin resistance, and, if such a correlation does exist, whether it is independent of adiposity. To investigate the possible existence of an independent correlation, we have assessed serum leptin levels and insulin resistance in Japanese diabetic and non-diabetic subjects by means of Homeostatic Model Assessment (HOMA-R). Sixty-four Japanese patients with Type 2 diabetes mellitus (DM) (33 men and 31 women) and 53 sex-, age-, and body mass index (BMI) matched non-diabetic adults (29 men and 24 women) were enrolled. The fasting plasma level of glucose (FPG) and the fasting serum levels of immunoreactive insulin (FIRI) and leptin were determined. Multiple linear regression analysis demonstrated that, in both male diabetic and male non-diabetic subjects, HOMA-R and BMI were independently correlated with serum leptin levels. In females, BMI, but not HOMA-R, was correlated to the serum levels of leptin in both groups. There was no statistically significant difference in the partial regression coefficients between male diabetic and male non-diabetic subjects. These results suggest that the correlation of HOMA-R to the serum levels of leptin in females is dependent on BMI. In males, the relationship between serum leptin levels and the insulin resistance was not affected by the extent of glucose intolerance. PMID- 11200944 TI - Sympathetic overactivity in the development of eyelid retraction in a patient with euthyroid Graves' disease evaluated by accommodation. AB - It is known that measurement of accommodation is useful to evaluate the sympathetic activity of intraocular muscles. To find if sympathetic overactivity is involved in eyelid retraction in euthyroid Graves' disease, we measured accommodation in two patients with this disease, whose serum concentrations of free T3, free T4 and TSH were within reference ranges. Accommodation was measured with a computer-assisted infrared optometer with an iriscoder, and the results were expressed as the change in the eye's refractive power (in diopters) in response to the movement of a target beam. In patient 1, the accommodation amplitude was low, indicating sympathetic overactivity. This amplitude rose to near the reference range when timolol maleate drops were used, and the eyelid retraction disappeared when guanethidine drops were given. During the use of guanethidine drops, accommodation remained normal. In patient 2, who had normal accommodation, eyelid retraction did not change with guanethidine administration, but improved with intravenous methylprednisolone pulse therapy. These two cases suggested that even in euthyroid Graves' disease, eyelid retraction is caused by sympathetic overactivity, and pulse therapy with methylprednisolone may be effective for eyelid retraction when guanethidine drops are not effective. PMID- 11200945 TI - Genetic and endocrinological evaluations of three 46,XX patients with congenital lipoid adrenal hyperplasia previously reported as having presented spontaneous puberty. AB - Congenital lipoid adrenal hyperplasia (CLAH) is an autosomal recessive disorder characterized by impaired synthesis of adrenal and gonadal steroids. It was demonstrated that loss-of-function mutations in the steroidogenic acute regulatory protein (StAR) gene cause CLAH and that 46,XX patients with CLAH develop spontaneous puberty. We had reported that three 46,XX patients with CLAH had presented spontaneous puberty and one of the patients had developed life threatening ovarian cysts, before the etiology of CLAH had been clarified. In the present study, we analyzed their StAR gene and demonstrated mutations. Endocrinological examinations of the patients revealed that serum LH and FSH levels and their responses to the LHRH stimulation were not exaggerated before the onset of puberty. Serum LH levels and its response to LHRH were increased during puberty, whereas serum FSH levels remained within the normal range. Serum estradiol increased after the administration of human menopausal gonadotropins in the pubertal patient, suggesting that the ovary might have another system than StAR to facilitate cholesterol transport into the mitochondria. Although the patients had menstrual cycles, they remained anovulatory, and the resultant increased secretion of LH was speculated to be responsible for the development of ovarian cysts. PMID- 11200946 TI - Rebound hypersecretion of GH following octreotide withdrawal due to liver dysfunction in an acromegalic patient. AB - Octreotide usually induces long-acting inhibition of GH secretion without rebound hypersecretion. We report a patient with acromegaly who showed rebound elevation of GH and insulin-like growth factor-1 (IGF-1) after octreotide withdrawal. The patient responded remarkably to octreotide therapy with normalization of GH and IGF-1 and shrinkage of pituitary macroadenoma. Octreotide therapy was stopped when he developed liver dysfunction. GH and IGF-1 were markedly elevated for two weeks after cessation of octreotide. PMID- 11200947 TI - Impairment of early insulin response after glucose load, rather than insulin resistance, is responsible for postprandial hyperglycemia seen in obese type 2 diabetes: assessment using nateglinide, a new insulin secretagogue. AB - The insulin secretory pattern as a phenotype of type 2 diabetes is an impairment in the rapid, pulsatile secretion of insulin in response to a rise in blood glucose after meal-intake. The restoration of endogenous rapid insulin secretion after oral glucose load was established for the first time by using nateglinide, which is a newly developed insulin secretagogue, in obese patients with type 2 diabetes mellitus. It was clearly demonstrated that with nateglinide, serum insulin levels were quickly raised, and glycemic response curves were almost normalized with the same amount of insulin secretion during 180 min. Therefore, the lack of rapid, pulsatile secretion of insulin in response to glycemic rise after oral glucose load, rather than insulin resistance, is responsible for postprandial glycemic response in obese type 2 diabetes patients. PMID- 11200948 TI - Horner's syndrome: recovery after surgical excision of intrarhoracic benign multinodular goiter. PMID- 11200949 TI - Is physical deconditioning a perpetuating factor in chronic fatigue syndrome? A controlled study on maximal exercise performance and relations with fatigue, impairment and physical activity. AB - BACKGROUND: Chronic fatigue syndrome (CFS) patients often complain that physical exertion produces an increase of complaints, leading to a greater need for rest and more time spent in bed. It has been suggested that this is due to a bad physical fitness and that physical deconditioning is a perpetuating factor in CFS. Until now, studies on physical deconditioning in CFS have shown inconsistent results. METHODS: Twenty CFS patients and 20 matched neighbourhood controls performed a maximal exercise test with incremental load. Heart rate, blood pressure, respiratory tidal volume, O2 saturation, O2 consumption, CO2 production, and blood-gas values of arterialized capillary blood were measured. Physical fitness was quantified as the difference between the actual and predicted ratios of maximal workload versus increase of heart rate. Fatigue, impairment and physical activity were assessed to study its relationship with physical fitness. RESULTS: There were no statistically significant differences in physical fitness between CFS patients and their controls. Nine CFS patients had a better fitness than their control. A negative relationship between physical fitness and fatigue was found in both groups. For CFS patients a negative correlation between fitness and impairment and a positive correlation between fitness and physical activity was found as well. Finally, it was found that more CFS patients than controls did not achieve a physiological limitation at maximal exercise. CONCLUSIONS: Physical deconditioning does not seem a perpetuating factor in CFS. PMID- 11200950 TI - Outcome of women admitted to hospital for depressive illness: factors in the prognosis of severe depression. AB - BACKGROUND: A previous study of women 9 months after discharge from in-patient treatment for depression found that low self-esteem as measured by a self-report questionnaire at admission was associated with a worse prognosis. This study investigates the womens' outcome more than 4 years after discharge and the continued prognostic relevance of self-esteem and other variables. METHOD: Fifty six women who had been admitted to hospital with major depression and studied in detail during their admission and 9 months following discharge were traced 4-5 years later. Possible prognostic factors were investigated in relation to time to recovery and recurrence, and to a global outcome measure. RESULTS: In keeping with other published work only 16 out of 52 (31%) women had recovered and remained well. Fifteen out of 52 (29%) subjects had experienced depressive symptoms for more than 70% of the follow-up time or died from unnatural causes. Low self-esteem scores recorded at the initial admission correlated with slow recovery but not subsequent recurrence of depression. The occurrence of one or more life events in the year preceding admission was associated with a better prognosis. CONCLUSIONS: The poor long-term prognosis of many women with severe depression was confirmed. Social factors, such as social support and marital relationships were less important for prognosis than in previous studies of less severely ill subjects. The prognostic value of self-esteem warrants further investigation and appears to have therapeutic implications. PMID- 11200951 TI - Unemployment and suicide: a cohort analysis of social factors predicting suicide in the US National Longitudinal Mortality Study. AB - BACKGROUND: The purpose of the study was to examine the effect of employment status measured at baseline on the risk of suicide by years of follow-up, using a large nationally representative sample of the US population. METHODS: Cox regression models were applied to data from the National Longitudinal Mortality Study, based on the 1979-1989 follow-up. In estimating the effect of baseline employment status on suicide, adjustments were made for baseline demographic and socio-economic variables. RESULTS: After 3 years of follow-up, unemployed men were a little over twice as likely to commit suicide as their employed counterparts. Among men, the lower the socio-economic status, the higher the suicide risk. Among women, in each year of follow-up, the unemployed had a much higher suicide risk than the employed. After 9 years of follow-up unemployed women were over three times more likely to kill themselves than their employed counterparts. CONCLUSIONS: Unemployment is strongly related to suicide, but this relationship is more enduring and stronger among women. For men, the unemployment effect is stronger at earlier years of follow-up. In women, unemployment increases the risk of suicide regardless of the number of follow-up years. The finding with regard to women disconfirms earlier research reports suggesting that unemployment affects suicide only in men. PMID- 11200952 TI - Fitness to plead. A prospective study of the inter-relationships between expert opinion, legal criteria and specific symptomatology. AB - BACKGROUND: Psychiatrists are asked to give opinions as to fitness to plead, a legal concept. There is a dearth of research into fitness to plead in the UK, with no prospective studies and no studies involving the comparison of fit and unfit subjects. In particular, there have been no investigations into the meaning of 'unfit to plead' in terms of psychiatric symptomatology, or as to the relative importance of each legal fitness criterion in psychiatrists' conclusions as to fitness. METHOD: The study comprised a prospective evaluation of 479 consecutive referrals to psychiatrists at court. Individual legal fitness criteria were examined as predictors of unfitness. Associations of unfitness, and of individual legal fitness criteria, were examined with Brief Psychiatric Rating Scale (BPRS) symptom scores. RESULTS: The two most important of the legal criteria in clinical decisions as to unfitness were whether the person could follow the proceedings of the trial or give adequate instructions to their solicitor. The legal criteria concerning trial were more predictive of unfitness than those concerning plea. Unfitness was significantly associated with the presence of positive psychotic symptomatology, in particular conceptual disorganization and delusional thinking, but not with symptoms of anxiety, depression or withdrawal. CONCLUSION: Unfitness is most significantly associated with symptoms affecting comprehension and communication. The fitness criteria could be simplified without loss of power. These results, predominantly concerned with mental illness, may not generalize to the mentally impaired. PMID- 11200953 TI - Age is no kinder to the better educated: absence of an association investigated using latent growth techniques in a community sample. AB - BACKGROUND: Higher education has been posited to protect against cognitive decline, either because the rate of decline is slower in the more highly educated or the start of decline is delayed. Latent growth models provide improved methodology to examine this issue. METHODS: The sample consisted of 887 participants aged 70-93 years in 1991 and followed up in 1994 and 1998. Latent growth models and standard regression techniques were used to examine the rate of cognitive decline in four cognitive measures while controlling for health status and sex. A delayed start model was examined by incorporating interaction effects in a regression model. RESULTS: Neither the latent growth models nor the regression techniques revealed a slower rate of decline for the more highly educated. The proportion of the highly educated showing no change was no larger than the proportion of the less well educated. There were no significant age by education interaction effects, no chronologically later accelerations in the rate of change as a function of education, and no differences in rate of decline between the first measurement interval and the second. CONCLUSIONS: Education may not protect against cognitive decline although it is associated with long-term individual differences in level of functioning. The discrepancy between our study and others may be attributable to attrition effects, follow-up length, sample age, scaling artefacts and negative publication bias. Most importantly, practice effects may favour the better educated and hence account for the supposed protective effect in many longitudinal studies of cognitive change. PMID- 11200954 TI - Diagnostic stability in subjects with multiple admissions for psychotic illness. AB - BACKGROUND: Although studies investigating changes in diagnosis between psychotic episodes have differed in design, some consistent findings have emerged. This study seeks to clarify and extend these findings by describing and comparing clinical and operationally defined diagnostic stability in a group of subjects with multiple episodes of functional psychotic illness. METHODS: The OPCRIT programme was applied to case notes of 204 subjects with multiple admissions for psychotic illness. Clinical and operationally defined diagnoses were compared and the spread and stability of diagnoses determined. RESULTS: An increase in the frequency of diagnosis of schizophrenia from initial to subsequent episodes was demonstrated. High levels of stability were found for schizophrenia (58 to 98%), moderate levels for affective disorders (24 to 83%), low levels for other non organic psychotic conditions (27 to 54%) and atypical psychosis (27 to 53%), and very low levels for schizoaffective disorder (5 to 39%) and other conditions (0 to 4%). CONCLUSIONS: The stability levels for schizophrenia and affective disorders are adequate, but the low levels for a range of other psychotic conditions raise questions regarding their predictive validity. PMID- 11200955 TI - A factor model of the functional psychoses and the relationship of factors to clinical variables and brain morphology. AB - BACKGROUND: Despite more than 100 years of study, there remains no definitive diagnostic validation of the functional psychoses. Factor analysis suggests the presence of three or more psychopathological syndromes in functional psychoses as a whole. The relationship between these factors and cerebral anatomy has been investigated in schizophrenia only. This study aimed to address the relationship of symptom factors to clinically important variables and cerebral anatomy in a sample of psychotic patients with a spread of diagnoses. METHODS: In a sample of patients with functional psychoses, symptom data was obtained on four consecutive admissions using the OPCRIT symptom checklist. OPCRIT data was used to generate operational diagnoses in accordance with pre-set criteria and a principle components analysis was performed on symptom data. Factor loadings were compared between each admission to examine factor stability over time. Factor scores at first admission were also correlated with clinical variables obtained from patients' case notes. From the sample of 204 patients, 64 subjects were recruited and underwent an MRI scan of the brain. Regional anatomical volumes were compared with diagnosis and factor loadings at first admission. RESULTS: A principal components analysis gave a four-factor solution of 'manic', 'depressive', 'disorganization' and 'reality distortion' factors at each admission. Factors showed a high degree of stability over the four admissions studied. The factors were significantly associated with several clinical variables. Three of the four factors were associated with a specific pattern of cerebral anatomy. CONCLUSIONS: This study suggests that factors may correspond to relatively specific disease processes underlying functional psychotic illness. We propose that the use of symptom factors may facilitate the investigation of the underlying mechanisms of psychotic illness. PMID- 11200956 TI - Dowrick et al. found no relationship between the scores on the Depression Attitude Questionnaire and GPs' ability to identify depressed individuals in the surgery. PMID- 11200957 TI - Ageing and mental health in a developing country: who cares? Qualitative studies from Goa, India. AB - BACKGROUND: While there is a growing body of epidemiological evidence on the prevalence of mental illnesses in late-life in developing countries, there is limited data on cultural perceptions of mental illnesses and care arrangement for older people. METHOD: This qualitative study used focus group discussions with older people and key informants to investigate the status of older people and concepts of late-life mental health conditions, particularly dementia and depression, in Goa, India. RESULTS: Vignettes of depression and dementia were widely recognized. However, neither condition was thought to constitute a health condition. Dementia was construed as a normal part of ageing and was not perceived as requiring medical care. Thus, primary health physicians rarely saw this condition in their clinical work, but community health workers frequently recognized individuals with dementia. Depression was a common presentation in primary care, but infrequently diagnosed. Both late-life mental disorders were attributed to abuse, neglect, or lack of love on the part of children towards a parent. There was evidence that the system of family care and support for older persons was less reliable than has been claimed. Care was often conditional upon the child's expectation of inheriting the parent's property. Care for those with dependency needs was almost entirely family-based with little or no formal services. Unsurprisingly, fear for the future, and in particular 'dependency anxiety' was commonplace among older Goans. CONCLUSIONS: There is a need to raise awareness about mental disorders in late-life in the community and among health professionals, and to improve access to appropriate health care for the elderly with mental illness. The study suggests directions for the future development of locally appropriate support services, such as involving the comprehensive network of community health workers. PMID- 11200958 TI - The molecular biology of Huntington's disease. AB - BACKGROUND: Huntington's disease (HD) is a fatal neurodegenerative disorder with an autosomal dominant mode of inheritance. It leads to progressive dementia, psychiatric symptoms and an incapacitating choreiform movement disorder, culminating in premature death. HD is caused by an increased CAG repeat number in a gene coding for a protein with unknown function, called huntingtin. The trinucleotide CAG codes for the amino acid glutamine and the expanded CAG repeats are translated into a series of uninterrupted glutamine residues (a polyglutamine tract). METHODS: This review describes the epidemiology, clinical symptomatology, neuropathological features and genetics of HD. The main aim is to examine important findings from animal and cellular models and evaluate how they have enriched our understanding of the pathogenesis of HD and other diseases caused by expanded polyglutamine tracts. RESULTS: Selective death of striatal and cortical neurons occurs. It is likely that the HD mutation confers a deleterious gain of function on the protein. Neuronal intranuclear inclusions containing huntingtin and ubiquitin develop in patients and transgenic mouse models of HD. Other proposed mechanisms contributing to neuropathology include excitotoxicity, oxidative stress, impaired energy metabolism, abnormal protein interactions and apoptosis. CONCLUSIONS: Although many interesting findings have accumulated from studies of HD and other polyglutamine diseases, there remain many unresolved issues pertaining to the exact roles of intranuclear inclusions and protein aggregates, the mechanisms of selective neuronal death and delayed onset of illness. Further knowledge in these areas will inspire the development of novel therapeutic strategies. PMID- 11200959 TI - The prevalence of depression in relation to cerebral atrophy and cognitive performance in 70- and 74-year-old women in Gothenburg. The Women's Health Study. AB - BACKGROUND: Hospital-based studies report that depression in the elderly is associated with brain atrophy. This notion could not be confirmed in a population study on 85-year-olds. We aimed to assess depression in relation to brain atrophy and cognition in 70- and 74-year-old women. METHODS; A representative sample of 70- and 74-year-old women (N = 501) was examined with a psychiatric examination including the Mini-Mental State Examination (MMSE), measuring global cognitive function, and computerized tomography (CT) of the brain (N = 268). Depression was diagnosed according to DSM-III-R. Previous depression was diagnosed by history and by information from previous examinations in this 24-year longitudinal study. RESULTS: The prevalence of depression was 11.6%, including 8.4% with major depression (MDD). Among those who were currently mentally healthy, 43.0% had a history of previous depression. Women with current MDD had lower scores on the MMSE than the mentally healthy women. This association was only found in women with a lower level of education. Current depressives, previous depressives and mentally healthy women without a history of depression did not differ on CT with regard to brain atrophy or white matter lesions. The association between MDD and lower cognitive performance was independent of the association of cognitive performance with structural brain changes on CT. CONCLUSIONS: Brain atrophy on CT is not associated with depression in the general population, despite the fact that individuals with depression have a worse cognitive performance. The finding that cognitive performance was not decreased in individuals with previous depression suggests that cognitive dysfunction is a state phenomenon in depression. PMID- 11200960 TI - Psychiatrists' diagnoses of subthreshold depression in old age: frequency and correlates. AB - BACKGROUND: Depressive syndromes not fulfilling the criteria for specified disorders (subthreshold depression, SD) may be clinically important. We aimed to study SD in old and very old age, in comparison with subjects with no depressive symptoms (NDS) and subjects with major depression (MD). METHODS: A community based random sample of 516 subjects, age 70 to 100 years and over, stratified by age and sex, was examined. All participants were investigated by psychiatrists and by geriatricians independently. RESULTS: In 16.5% (N = 85) of the study subjects SD was identified. Study subjects with SD had, similarly to the subjects with MD, significantly more somatic diagnoses and used more somatic as well as psychotropic medications than the subjects with NDS. Self-ratings and observer ratings of depression indicated that SD was a milder depressive state than MD. CONCLUSIONS: Compared with MD, SD is probably a milder form of depression. The increased use of psychotropic medications indicates that at least a portion of these individuals have a disorder requiring treatment. One of the characteristics of SD is co-morbidity with somatic illnesses and physical disability. PMID- 11200961 TI - What contributes to depression in Parkinson's disease? AB - BACKGROUND: Depression is a common problem in patients with Parkinson's disease, but its mechanism is poorly understood. It is thought that neurochemical changes contribute to its occurrence, but it is unclear why some patients develop depression and others do not. Using a community-based sample of patients with Parkinson's disease, we investigated the contributions of impairment, disability and handicap to depression in Parkinson's disease. METHODS: Ninety-seven patients seen in a population-based study on the prevalence of Parkinson's disease completed the Beck Depression Inventory (BDI). Clinical and historical information on symptoms and complications of Parkinson's disease were obtained from the patients by a neurologist. In addition, clinician and patient ratings of disability on the Schwab and England scale were obtained and a quality of life questionnaire was completed. RESULTS: Moderate to severe depression (BDI > or = 18) was reported by 19.6% of the patients. Higher depression scores were associated with advancing disease severity, recent self-reported deterioration, higher akinesia scores, a mini-mental score of < 25 and occurrence of falls. Disability as rated by the neurologist accounted for 34% of the variance of depression scores. Self-reported impairment of cognitive function and the feeling of stigmatization accounted for > 50% of the variance of depression scores. CONCLUSIONS: Depression in patients with Parkinson's disease is associated with advancing disease severity, recent disease deterioration and occurrence of falls. Regression analysis suggests that depression in Parkinson's disease is more strongly influenced by the patients' perceptions of handicap than by actual disability. The treatment of depression should therefore be targeted independently of treatment of the motor symptoms of Parkinson's disease, and consider the patients' own perception of their disease. PMID- 11200962 TI - Acute tryptophan depletion in schizophrenia. AB - BACKGROUND: Brain 5-hydroxytryptamine (5-HT) function is implicated in the pathophysiology of schizophrenia and the action of new generation antipsychotic drugs. By the method of acute tryptophan depletion (ATD) 5-HT can be selectively manipulated. The aim of this study was to examine the effects of ATD on symptoms, mood and cognition in schizophrenic patients. METHODS: Twenty-eight schizophrenic patients participated in a within subject, double-blind, placebo-controlled counterbalanced cross-over study. Patients with a concurrent DSM-IV axis I diagnosis were excluded. Symptoms, mood and cognitive function were evaluated following ATD or ingestion of a control drink. RESULTS: The depleting drink significantly reduced plasma total and free tryptophan. Tryptophan/LNAA ratios did not alter with the administration of the control drink, but differed significantly with ATD; however there was no significant change in tyrosine/LNAA ratio. ATD led to impairment in executive function that was dependent upon the order of administration. Tests of sustained attention, speed of processing, and everyday memory were not affected. No effects were observed on subjective mood ratings, movement disorders or PANSS scores. CONCLUSIONS: Acute tryptophan depletion selectively alters cognition in schizophrenia, but has no effect on symptoms, mood ratings or movement disorders. PMID- 11200963 TI - Implications of impulsive and affective symptoms for serotonin function in bulimia nervosa. AB - BACKGROUND: Bulimic, impulsive and depressive syndromes have all been associated with abnormalities in brain serotonin (5-hydroxytryptamine; 5-HT) mechanisms. METHODS: We had 26 bulimic women and 22 normal-eater women report impulsive, affective, self-destructive and bulimic symptoms, and then provide serial blood samples for measurement of: [3H]-paroxetine binding in platelets; and, prolactin (PRL) responses following oral meta-chlorophenylpiperazine (m-CPP). RESULTS: Bulimic status was associated with markedly reduced density of paroxetine-binding sites, modest blunting of m-CPP stimulated PRL response, and greater nausea following m-CPP. Biological variables did not co-vary with most psychopathological or eating-symptom indices. However, there were inverse associations (in bulimic women only) between scores indicating impulsivity (largely 'unreflectiveness') and density of platelet 5-HT uptake sites. CONCLUSIONS: Our observations link bulimia nervosa to altered 5-HT functioning, and suggest that there may be a relatively symptom-specific association between impulsivity and reduced 5-HT reuptake. PMID- 11200964 TI - Causal attributions for somatic sensations in patients with chronic fatigue syndrome and their partners. AB - BACKGROUND: Patients with chronic fatigue syndrome (CFS) often make somatic attributions for their illness which has been associated with poor outcome. A tendency to make somatic attributions in general may be a vulnerability factor for the development of CFS. METHODS: This cross-sectional study based on self report questionnaire data aimed to investigate the type of attributions for symptoms made by patients with CFS and to compare this to attributions made by their partners. It was hypothesized that patients with CFS would make more somatic attributions for their own symptoms than control subjects and that partners of patients with CFS would make more somatic attributions for their ill relative's symptoms but would be similar to controls regarding their own symptoms. Fifty patients with CFS were compared to 50 controls from a fracture clinic in the same hospital and 46 relatives living with the patients with CFS. A modified Symptom Interpretation Questionnaire was used to assess causal attributions. RESULTS: CFS patients were more likely to make somatic attributions for their symptoms. The relatives of patients with CFS made significantly more somatic attributions for symptoms in their ill relative. However, they were like the fracture clinic controls in terms of making predominantly normalizing attributions for their own symptoms. CONCLUSIONS: The data support modification of existing cognitive behavioural treatments for CFS to investigate whether addressing partners' attributions for patients' symptoms improves recovery in the patient. Furthermore, a tendency to make somatic attributions for symptoms may be a vulnerability factor for the development of CFS. PMID- 11200965 TI - Mortality in the offspring of individuals living along the radioactively contaminated Techa River: a descriptive analysis. AB - From 1949 onwards, radioactive waste was released into the Techa River in the southern Urals and the population living along the river was exposed to ionising radiation. Relocation of these people did not start until several years later, causing many individuals to be exposed to substantial doses from internal and external radiation. The identification and follow-up of the exposed individuals started more than 40 years ago and is still continuing. The Techa River offspring cohort (TROC) that has recently been established, comprises 10,459 children born to at least one parent living along the Techa River during the period 1950-1992. Of these children, 3,897 were born during the period of highest release, i.e. between 1950 and 1956 and might thus have been exposed in utero. A total of 1,103 individuals have since died mainly due to infectious and respiratory diseases, injury and poisoning. Only 25 cases were identified as having died of a malignant condition. The radioactive contamination of the Techa River in the southern Urals gives a unique possibility to study the adverse effects of protracted exposure to ionising radiation in a large well-described cohort. The Techa River offspring cohort will make it possible to study the effects on those exposed in utero or early in life and the follow-up of the cohort in the future is, therefore, of great importance. Comparisons with other cohorts of humans exposed early in life, will increase our knowledge in this field of research. PMID- 11200966 TI - Comparing different methods of estimating cosmic radiation exposure of airline personnel. AB - In Europe, several studies are currently underway to investigate the cancer risk of pilots and cabin crew exposed to low-level ionizing radiation of cosmic origin. Although no individualized exposure measurements of airline personnel are available, exposure assessment based on job history data is feasible. However, there is a marked variability in the level of detail of these data between studies in different countries and between subcohorts in national studies raising the issue of comparability of exposure estimation. In this paper we investigate the comparability of several methods of exposure assessment in a large German cohort of pilots and cabin crew. We found that the correlation between the estimates obtained by the four approaches analysed, is relatively high, ranging from 0.85 to 0.97. The precision attainable in the exposure assessment is higher than in many other epidemiological studies but can be refined further with simulation studies and comparison with ongoing and future on-board measurement programmes. PMID- 11200967 TI - Extremely low frequency magnetic fields in residences in Germany. Distribution of measurements, comparison of two methods for assessing exposure, and predictors for the occurrence of magnetic fields above background level. AB - We examined the results of 1,835 magnetic field measurements in German residences conducted between November 1997 and September 1999. The measurements were part of an epidemiological study on the relationship between magnetic fields and childhood leukemia. We performed a fixed-location measurement of the magnetic field at 50 Hz and 16 2/3 Hz (frequency of the German railway system) over 24 h in the child's bedroom in the residence of each study participant. In addition, we conducted a second 24 h-measurement in the living room at 50 Hz, and spot measurements while walking through all rooms of the respective dwelling. Median 50 Hz magnetic fields above 0.2 muT were found to be infrequent in Germany (only 1.4% of all residences). Fields produced by high-voltage power lines (123-420 kV) were lower than expected: the median magnetic field was above 0.2 muT in only 8 (32.0%) of 25 residences located 50 m or closer to a high-voltage power line indicating that power lines in Germany are usually run well below the maximum power load. We found that magnetic fields were correlated with the type of residence and higher magnetic fields were measured in apartment buildings. There was also some evidence for a positive correlation between magnetic fields and traffic density and an inverse association between magnetic fields and family net income. The 24 h-magnetic field measurements correlated well with the spot measurements (r>0.7). However, when dichotomized with a cut-off point of 0.2 muT, there was only a poor agreement between the two measurement methods. A loss of the strength of the association after categorization was also observed when comparing the arithmetic mean and median of the same 24 h-measurement. In summary, these analyses give a valuable overview of magnetic field distributions in German residences. PMID- 11200968 TI - Projection of cancer risks from the Japanese atomic bomb survivors to the England and Wales population taking into account uncertainty in risk parameters. AB - Generalized relative risk models, with adjustments to the relative risk for time after exposure and age at exposure and incorporating a linear-quadratic dose response, were fitted to the latest (Life Span Study Report 12) Japanese atomic bomb survivor cancer mortality data using Bayesian Markov Chain Monte Carlo methods, taking account of random errors in the DS86 dose estimates. The resulting uncertainty distributions in the relative risk model parameters were used to derive uncertainties in population cancer risks for a current UK population. Following an assumed administered dose of 1 Sv, leukaemia mortality risks were estimated to be 1.93x10(-2) Sv(-1) (95% CI 1.14, 3.38), or 0.44 years of life lost Sv(-1) (95% CI 0.22, 0.94). Following an assumed administered dose of 1 Sv, solid cancer mortality risks were calculated to be 10.36x10(-2) Sv(-1) (95% CI 8.41, 12.42), or 1.38 years of life lost Sv(-1) (95% CI 1.11, 1.68). In general, solid cancer risks were very similar to those predicted by classical likelihood-based methods; however, leukaemia risks were somewhat higher, by 10 35%, than those predicted by classical likelihood-based methods. This is so in both cases, irrespective of whether or not adjustments are made in these likelihood-based fits for the effects of measurement errors, and the discrepancy for leukaemia tends to be greater at higher doses. Overall, cancer risks predicted by Bayesian Markov Chain Monte Carlo methods are similar to those derived by classical likelihood-based methods and which form the basis of established estimates of radiation-induced cancer risk. PMID- 11200969 TI - Analysis of lung tumour risk in radon-exposed rats: an intercomparison of multi step modelling. AB - Three carcinogenesis modelling groups have both jointly and separately applied a multi-step carcinogenesis model with clonal expansion to one data set of lung tumours in rats exposed to radon (CEA, France). This study was designed to investigate the differences in modelling approach and fitting procedures used by the three groups in detail, and to explore possible discrepancies in the results. Using the same model assumptions and a (linear) radiation dependence on the first model step only, the three groups arrived at identical best fits, proving that the mathematical formalisms and fitting procedures do not lead to different results. However, when each group was allowed to find its own preferred fit for this data set, all three found a significantly better, but different fit to the data. All solutions indicated radiation to be an initiating agent and found additional radiation action necessary. The character of this additional radiation dependence, however, could not be unambiguously pinpointed. Tumour incidence data were described equally well when radiation dependence was taken into account in clonal expansion ("promotion") or in the second mutational step ("transformation"); extension to three model stages also resulted in an adequate description. The study showed that, although the three groups used one carcinogenesis model in principle, different model assumptions and/or different methods of finding the "best fit" could result in different descriptions of experimental data. This implies that on statistical grounds, different interpretations can be given for the action that radiation had in this data set. Different data, i.e. other data sets with age-dependent tumour data and/or information from cellular radiobiology experiments, are needed to specifically pin down the radiation dependence in the multi-step carcinogenesis process. PMID- 11200970 TI - Time course solutions of the Sax-Markov binary eurejoining/misrejoining model of DNA double-strand breaks. AB - The Sax-Markov binary eurejoining/misrejoining (SMBE) model is a stochastic representation of Sax's breakage-and-reunion mechanism of misrejoining DNA double strand breaks (DSBs). In this model, to approximate DSB misrejoining probabilities that decrease with increasing distance, the nucleus is treated as a collection of eta isolated nuclear subvolumes called sites; DSB free ends within the same site interact with a probability that is independent of distance, and DSB free ends within different sites never interact. In our previous work, SMBE steady-state solutions were used to estimate eta from a combination of high-dose PFGE (pulsed-field gel electrophoresis) data and moderate-dose chromosomal aberration data. Here, analytic SMBE transient solutions (i.e., time courses of DSBs and misrejoinings) are derived and used to estimate eta from various sets of misrejoining DSB kinetic data. The time courses are multiexponentials with rate constants kappa, 6kappa, 15kappa, ... j(2j-1)kappa corresponding to different nuclear site states and not different types of DSBs. For example, the kappa component corresponds to nuclear sites with two DSB free ends and thus only one possible rejoining interaction, and the 6kappa component corresponds to sites with four DSB free ends and thus six (four choose two) potential rejoining interactions--four of these six potential interactions lead to a final state of two misrejoinings and the other two of six lead to a final state of correct repair (unrejoinable DSBs are not represented in the SMBE model). The SMBE time course solutions provide site number estimates that fall in the range of eta approximately equals 10-100 for premature chromosome condensation (PCC) data and eta approximately equals 1,000 for PFGE data. PMID- 11200972 TI - Effect of potassium (K) supply on the uptake of 137Cs by spring wheat (Triticum aestivum cv. Tonic): a lysimeter study. AB - A lysimeter experiment was carried out on a relatively infertile soil to examine the effect of potassium fertiliser application on the uptake of radiocaesium by spring wheat. Porous ceramic cups were used to obtain samples of soil solution. Results showed that the uptake of radiocaesium by spring wheat was reduced by the addition of potassium. However this inhibitory effect was less marked at later stages of plant growth due to factors such as the spatial variability of potassium within the soil, differences in root distribution down the soil profile and age-related demand for potassium by the plant. There was some evidence that a negative power function could be used to describe the relationship between the concentration of 137Cs in the plant and concentrations of potassium or 137Cs:K quotients in soil solution over the whole experimental period. Practical implications of potassium fertilisation in terms of reducing uptake of radiocaesium by crops are discussed. PMID- 11200971 TI - Biomarkers of genetic damage and inflammation in blood and bronchoalveolar lavage fluid among former German uranium miners: a pilot study. AB - Former East German uranium miners who are known to have been exposed to radon are estimated to be at high risk for lung carcinogenesis. Among these miners over 200 occupationally caused lung cancer cases are expected to occur each year, resulting in a total of 7,000-24,000 excess lung cancer cases in the coming years. It is still unknown whether there is a correlation between biomarkers and the exposure of the uranium miners to ionizing radiation that might enable us to trace those miners with high lung cancer risk. The primary aim of this pilot study was to test the possibility of performing a biomarker study in this unique cohort of former uranium miners in spite of several limitations that had to be taken into consideration when comparing them with healthy controls, such as old age, age-dependent diseases and potential confounding artefacts from dissimilar smoking patterns. The second aim was to test a range of biomarkers for DNA damage and inflammation in leukocytes and bronchoalveolar fluid for their ability to detect biological effects. In this cohort of miners we found an increased frequency of chromosomal aberrations in blood lymphocytes and an increased prevalence of both fibronectin and tumour necrosis factor alpha in the bronchoalveolar fluid. PMID- 11200973 TI - Analysis of the contribution of forest pathways to the radiation exposure of different population groups in the Bryansk region of Russia. AB - The experience gained in the aftermath of serious radiation accidents shows that forests are an important source of external and internal exposure of the affected population. This paper presents the results of an assessment of the major radiological consequences for forests of Russia, most heavily contaminated after the Chernobyl nuclear power plant (ChNPP) accident. Illustrated in the Novozybkovsky district of the Russian Federation, the significance of different forest exposure pathways is estimated and the doses resulting from forest pathways are compared with the doses from agricultural products. It has been found that the contribution of mushrooms and berries to the internal doses of the population, relative to the doses from agricultural products, varied from 10-15% in 1987 to 40-45% in 1996. The results indicate large differences in internal exposure of members of the "critical groups" and "normal population", increasing with time after deposition. Data are presented that give information on the contribution of forests to the collective doses of inhabitants of the area under consideration. It has been shown that for 10 years after the accident (1987 1996), the contribution of forest products to the collective dose of the rural population living in contaminated forests of the Novozybkovsky district, amounts to about 20% (213 person Sv) of the total collective dose of internal and external exposures. However, a potential impact of these products including the dose from exported products is much higher and might reach 659 person Sv. It has been found that in the long-term after the ChNPP accident, serious attention should be given to forest countermeasures, and restoration strategies should be selected on the basis of a combined analysis of the effectiveness of forest and agricultural countermeasures. PMID- 11200974 TI - Thermoluminescence dating of terrazzo from the monastery church of Tegernsee (Bavaria, Germany) using the 210 degrees C TL peak of quartz. AB - Thermoluminescence (TL) is one of the most important physical methods used in archaeometry for dating ceramics. In this study the newly developed procedures based on the use of the 210 degrees C TL peak of quartz were applied to well dated bricks of the church of the Tegernsee monastery in Bavaria. The resulting TL ages obtained from these well-dated bricks were used as a reference for selection of the suitable measurement procedure and to test the precision of the measurements and the accuracy of the technique. The optimized procedure was applied to the terrazzo fragments from the monastery church. The TL results provide a new understanding of the architectural history of the church. The improved measurement procedure including various dose evaluation techniques and the components of the annual dose assessment are described. PMID- 11200976 TI - The relationship between dietary intake, exercise, energy balance and the space craft environment. AB - Space flight is associated with the loss of skeletal muscle, principally from muscles with anti-gravity functions. Examination of data across different missions can permit a distinction to be made between true microgravity responses and what are mission-specific responses. Protein metabolism has been investigated on six missions, four short-term [Shuttle missions Space Life Sciences 1 (1991, SLSI), Space Life Sciences 2 (1993, SLS2), Deutsche-2 (1993, D2) and the Life and Microgravity Sciences (1996, LMS)] and two long-term missions (Skylab 1993 and NASA/MIR, 1996-1998). Measurements made include dietary intake (six missions), nitrogen balance (four missions), whole-body protein kinetics with [15N]glycine as the tracer (four missions) and cortisol excretion (three missions). Also available for comparison are bed rest studies with and without exercise. The purpose of this paper is to see what can be learnt about the muscle loss problem by comparing metabolic results across the six missions for which data are available and against bed rest. The analysis suggests that there is a linkage between the inability to maintain energy balance and exercise, and the connection is the decreased efficiency of removal of the metabolic by-products of exercise (heat, CO2) during space flight. PMID- 11200975 TI - Dietary instead of pharmacological management to counter the adverse effects of physiological adaptations to space flight. AB - The development of pharmacological counter-measures to the adverse effects of physiological adaptation to microgravity has received relatively more attention than alternatives such as dietary management. The manipulation of dietary cation anion balance, and its subsequent effects on acid-base metabolism, have been routinely used for some time in managing domestic animal health. More recently, dietary intake by humans of alkalinizing potassium salts has been demonstrated to exert profound beneficial effects on calcium balance, bone mineralization, predisposition to calcium oxalate nephrolithiasis, and overall nitrogen balance. Dietary sodium restriction has also been shown to improve calcium balance, bone mineralization, and the effectiveness of neurohumoral defenses against orthostatic hypotension. It is proposed that these simple alterations in the astronauts' diets may be easily implemented to lessen the adverse effects of physiological adaptations to space flight, and to enhance or even replace prescribed pharmacological counter-measures. PMID- 11200977 TI - Gravity and thermoregulation: metabolic changes and circadian rhythms. AB - Gravity appears to alter thermoregulation through changes in both the regulated level of body temperature and the rhythmic organization of temperature regulation. Gravity has been hypothesized to have an associated metabolic cost. Increased resting energy expenditure and dietary intake have been observed in animals during centrifuge experiments at hypergravity. Thus far, only animals have shown a corresponding reduction in metabolism in microgravity. Altered heat loss has been proposed as a response to altered gravitational environments, but remains documented only as changes in skin temperature. Changes in circadian timing, including the body temperature rhythm, have been shown in both hypergravity and microgravity, and probably contribute to alterations in sleep and performance. Changes in body temperature regulation may result from circadian disturbance, from the direct or indirect actions of gravity on the regulated temperature, or from changes in thermoregulatory effectors (heat production and heat loss) due to altered gravitational load and convective changes. To date, however, we have little data on the underlying thermoregulatory changes in altered gravity, and thus the precise mechanisms by which gravity alters temperature regulation remain largely unknown. PMID- 11200978 TI - Are energy metabolism alterations involved in cardiovascular deconditioning after weightlessness? An hypothesis. AB - The physiopathogenesis of the cardiovascular deconditioning syndrome observed after actual and simulated microgravity is still under debate, despite numerous studies conducted on the role of blood volume, hormones involved in its regulation, sympathetic nervous system, baroreflexes and venous compliance. Orthostatic intolerance, a reduced exercise capacity and an increased heart rate at rest characterize this syndrome. Recent data suggest, first, the presence of a complex loop between the sympathetic nervous system, carbohydrate metabolism (insulin) and leptin hormone and, second, that this loop, an overall reflection of energy metabolism, participates in cardiovascular regulation. After a resume of studies conducted on fuel homeostasis during actual and simulated microgravity, the possible implications of energy metabolism in the development of the cardiovascular deconditioning syndrome will be discussed. PMID- 11200979 TI - Orthostatic intolerance and the postural tachycardia syndrome: genetic and environment pathophysiologies. Neurolab Autonomic Team. AB - Orthostatic intolerance is a common problem for inbound space travelers. There is usually tachycardia on standing but blood pressure may be normal, low or, rarely, elevated. This condition is analogous to the orthostatic intolerance that occurs on Earth in individuals with orthostatic tachycardia, palpitations, mitral valve prolapse, and light-headedness. Our studies during the Neurolab mission indicated that sympathetic nerve traffic is raised in microgravity and that plasma norepinephrine is higher than baseline supine levels but lower than baseline upright levels. A subgroup of patients with familial orthostatic intolerance differ from inbound space travelers in that they have an alanine-to-to-proline mutation at amino acid position 457 in their norepinephrine transporter gene. This leads to poor clearance of norepinephrine from synapses, with consequent raised heart rate. Clinical features of these syndromes are presented. PMID- 11200980 TI - Integrated physiology in space--challenges for the future: the Bad Honnef Recommendations. PMID- 11200981 TI - Orthostatic stress is necessary to maintain the dynamic range of cardiovascular control in space. AB - In the upright position, gravity fills the low-pressure systems of human circulation with blood and interstitial fluid in the sections below the diaphragm. Without gravity one pressure component in the vessels disappears and the relationship between hydrostatic pressure and oncotic pressure, which regulates fluid passage across the capillary endothelium in the terminal vascular bed, shifts constantly. The visible consequences of this are a puffy face and "bird" legs. The plasma volume shrinks in space and the range of cardiovascular control is reduced. When they stand up for the first time after landing, 30-50% of astronauts suffer from orthostatic intolerance. It remains unclear whether microgravity impairs cardiovascular reflexes, or whether it is the altered volume status that causes the cardiovascular instability following space flight. Lower body negative pressure was used in several space missions to stimulate the cardiovascular reflexes before, during and after a space flight. The results show that cardiovascular reflexes are maintained in microgravity. However, the astronauts' volume status changed in space, towards a volume-retracted state, as measurements of fluid-regulating hormones have shown. It can be hypothesized that the control of circulation and body fluid homeostasis in humans is adapted to their upright posture in the Earth's gravitational field. Autonomic control regulates fluid distribution to maintain the blood pressure in that posture, which most of us have to cope with for two-thirds of the day. A determined amount of interstitial volume is necessary to maintain the dynamic range of cardiovascular control in the upright posture; otherwise orthostatic intolerance may occur more often. PMID- 11200982 TI - Renal adjustments to microgravity. AB - During a 10-day shuttle mission, the diuretic and natriuretic responses to an i.v. isotonic saline load were attenuated and plasma noradrenaline concentration increased after 5-6 days of microgravity compared with to those of the acute supine position prior to flight. Furthermore, on the Russian space station Mir, we have observed that renal fluid excretion in two astronauts following an oral water load of 600 ml was attenuated compared with that of the acute supine position on the ground. Since it was surprising that the renal responses to isotonic saline loading and to an oral water load were attenuated during space flight, we carried out a study in Japan employing the same water load protocol as in space in eight subjects after 19 days of head-down bed rest. The results indicate that the urinary flow rate following the water load of 600 ml is the same as in the acute supine position when the subjects have not been subjected to bed rest. This is in contrast to the results of the astronauts in space. The attenuated renal responses during space-flight could be explained by an increase in renal sympathetic nervous activity and in the elevated level of the renin angiotensin-aldosterone axis observed during the space shuttle flight. This space induced activation of antinatriuretic mechanisms could have been caused by early in-flight reduction in total and central blood volume. Based on our unexpected results from space, in future studies we will focus on the mechanisms of renal fluid excretion during space-flight. An experiment with the participation of American, European, Russian, and Japanese researchers has been selected in this regard for the early phase of the International Space Station. PMID- 11200983 TI - Body fluid regulation in micro-gravity differs from that on Earth: an overview. AB - Similar to the response to central hypervolemic conditions on Earth, the shift of blood volume from the legs to the upper part of the body in astronauts entering micro-gravity should, in accordance with the Henry-Gauer mechanism, mediate diuresis and natriuresis. However, fluid balance and kidney function experiments during various space missions resulted in the surprising observation that the responses qualitatively differ from those observed during simulations of hypervolemia on Earth. There is some evidence that the attenuated responses of the kidney while entering weightlessness, and also later during space flight, may be caused by augmented fluid distribution to extravascular compartments compared to conditions on Earth. A functional decoupling of the kidney may also contribute to the observation that renal responses during exposure to micro-gravity are consistently weaker than those during simulation experiments before space flight. Deficits in body mass after landing have always been interpreted as an indication of absolute fluid loss early during space missions. However, recent data suggest that body mass changes during space flight are rather the consequences of hypocaloric nutrition and can be overcome by improved nutrition schemes. Finally, sodium-retaining humoral systems are activated during space flight and may contribute to a new steady-state of metabolic balances with a pronounced increase in body sodium compared to respective conditions on Earth. A revision of the classical "micro-gravity fluid shift" scheme is required. PMID- 11200984 TI - Anaerobic exercise increases fat-free mass but not extracellular water during prolonged, 6 degrees-head-down bed rest. PMID- 11200985 TI - Head-down tilt bed rest and immune responses. AB - Head-down tilt bed rest (HDT) is used as a model for studying the physiological changes occurring in weightlessness during spaceflight. In the present study, eight volunteers were subjected to a strict HDT of -6 degrees for 42 days. Blood samples were obtained 37 and 13 days before, at days 13, 34, and 41 during, and 12, 33, and 47 days after HDT. FACScan analysis was used to determine cell subpopulations. Plasma was used to quantify various circulating hormone levels. Whole blood and reconstituted blood were stimulated with various activators such as phytohaemagglutinin-P (PHA), PHA combined with phorbol-12-myristate 13-acetate (PMA), anti-CD2, anti-CD3, and lipopolysaccharide. Supernatants were collected and analysed for the interleukins IL-1beta, IL-2, IL-6, and IL-10, interferon gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). The total number of T lymphocytes and monocytes did not change significantly, whereas the number of polymorphonuclear cells increased during HDT. The percentage of CD2+ and CD3+ cells was increased at day 35 of HDT. The percentage and total number of natural killer cells (CD2+/CD3-/CD56+) was increased 12 days before and 14 days after HDT. TNF-alpha secretion did not change significantly during HDT. IL-2, IL-10 and IFN-gamma were increased at day 34 of HDT. IL-1beta levels were increased before and during HDT compared to post-HDT measurements. No significant changes were observed in plasma immunoglobulin, complement factors and other factors of the inflammatory system. Prolactin levels increased slightly but significantly at day 35 of HDT, thyreotropin and growth hormone levels remained virtually unchanged. Cortisol decreased slightly but significantly over the entire duration of the study. The changes observed during HDT do not indicate that the immune system is blunted, and these changes do not seem to correlate with the duration of HDT. Taken together these results show that a HDT does not reproduce the changes in immune responses observed after spaceflight. PMID- 11200986 TI - Nutrient supply during recent European missions. AB - An inadequate nutrient intake during space flight may compromise the crewmembers' health status. In fact, during recent European missions (D-2, EuroMIR 94 and EuroMIR 95), monitoring of the astronauts' food intake revealed that they had a deficient energy, fluid, and calcium intake and an excessive sodium consumption compared to the dietary reference intakes for earthbound conditions. Inappropriate amounts of these nutrients have a considerable impact on body fluid regulation, the cardiovascular system and on calcium and bone metabolism, especially bone mineral density, which are all stressed by the microgravity environment. Provision of adequate nutrition especially when facing long-term space flights is therefore one of the foremost challenges. Therefore, for the German MIR 97 mission, we considered the data obtained from previous European missions to devise a constant and controlled nutrient intake that matched the earthbound dietary reference intake values in our experiments. Specific markers indicated that bone formation continually declined and bone resorption increased in the MIR 97 astronaut. This suggests that the nutritional criteria chosen for the subjects remaining on Earth may be inadequate for extended space missions. Therefore, more emphasis has to be placed on investigating the effects of a deficient nutrient intake on astronauts during exposure to microgravity, to manage their nutritional care appropriately during long-term missions. PMID- 11200987 TI - Adaptation of the human endocrine system to microgravity in the context of integrative physiology and ageing. AB - This review deals with changes occurring in space in different endocrine systems. Sections are dedicated to hormones involved in bone remodelling, the hypothalamic pituitary-adrenal axis, the hypothalamic-pituitary-thyroid axis, pancreatic hormones, the hypothalamic-pituitary-gonadal axis and the hypothalamic-pituitary somato-mammotropic system. In space, most systems - especially those regulating bone/muscle metabolism and reproduction - undergo changes resembling those observed during senescence, but recover within weeks or months after return. This suggests space as a possible experimental model for the study of "reversible ageing processes". Studying ageing through space technology might give us the opportunity to combine the holistic view of integrative physiology with the most ambitious goal of the present scientific community, i.e. to yield successful ageing by promoting chronic disease prevention studies and by optimizing safe, anti-ageing therapeutic protocols. PMID- 11200988 TI - Modulation of red cell mass by neocytolysis in space and on Earth. AB - Astronauts predictably experience anemia after return from space. Upon entering microgravity, the blood volume in the extremities pools centrally and plasma volume decreases, causing plethora and erythropoietin suppression. There ensues neocytolysis, selective hemolysis of the youngest circulating red cells, allowing rapid adaptation to the space environment but becoming maladaptive on re-entry to a gravitational field. The existence of this physiologic control process was confirmed in polycythemic high-altitude dwellers transported to sea level. Pathologic neocytolysis contributes to the anemia of renal failure. Understanding the process has implications for optimizing erythropoietin-dosing schedules and the therapy of other human disorders. Human and rodent models of neocytolysis are being created to help find out how interactions between endothelial cells, reticuloendothelial phagocytes and young erythrocytes are altered, and to shed light on the expression of surface adhesion molecules underlying this process. Thus, unraveling a problem for space travelers has uncovered a physiologic process controlling the red cell mass that can be applied to human disorders on Earth. PMID- 11200990 TI - Multiple epiphyseal dysplasia: radiographic abnormalities correlated with genotype. AB - Multiple epiphyseal dysplasia (MED) is an osteochondrodysplasia characterized clinically by mild short stature and early-onset degenerative joint disease and radiographically by epiphyseal hypoplasia/dysplasia. MED is genetically heterogeneous, with autosomal dominant cases resulting from mutations in at least three genes: the cartilage oligomeric matrix protein (COMP) gene (EDM1) and the COL9A2 (EDM2) and COL9A3 (EDM3) genes of type IX procollagen. We present here a comparison of the radiographic phenotypes of MED patients with type IX collagen gene mutations and those with COMP gene mutations. We reviewed radiographs from two patients with MED produced by COMP mutations, two families with COL9A2 mutations, and one family with a mutation in COL9A3. The data demonstrated that the patients with type IX collagen defects had more severe joint involvement at the knees and relative hip sparing, while the patients with COMP mutations had significant involvement at the capital femoral epiphyses and irregular acetabuli. This pattern of joint involvement was consistent regardless of overall degree of severity of the phenotype. PMID- 11200989 TI - Can daily centrifugation prevent the haematocrit increase elicited by 6-degree, head-down tilt? AB - A measure to counteract the effects of low or zero gravity is required for long term space flight, such as the manned Mars mission scheduled by the National Aeronautics and Space administration (NASA) for 2014. We conducted a series of centrifugation experiments with humans, using a short-arm centrifuge (radius 1.8 m, made by First Medical Co., Tokyo, Japan). We employed 6-degree, head-down tilt (HDT) for 4 days to simulate space flight. Ten healthy male volunteers underwent 4-day HDT and a 2-G daily centrifuge load for 60 min in the +Gz direction and measurements, such as haematocrit, 24-h urine volume, body weight and electrocardiogram (ECG) were made. There was no significant increase in the haematocrit during the HDT period, although our previous studies had shown a significant increase during HDT. A 60-min daily load of +2 Gz appears to be effective in reversing the haematocrit increase due to 4-day HDT. PMID- 11200991 TI - Spondylo-meta-epiphyseal dysplasia, short limbs, abnormal calcification type: a new case with severe neurological involvement. AB - A case of an affected girl with spondylo-meta-epiphyseal dysplasia (SMED) is reported. The disease was detected at birth as a congenital dysplasia with generalized lesions. At 10 months of age, abnormal calcifications appeared in both wrists. The patient evolved with severe growth retardation and multiple neurological and respiratory complications, followed by death at 21 months of age. PMID- 11200992 TI - Radiographic findings and Gs-alpha bioactivity studies and mutation screening in acrodysostosis indicate a different etiology from pseudohypoparathyroidism. AB - Acrodysostosis is an uncommon skeletal dysplasia associated with nasal hypoplasia, midface deficiency, severe brachydactyly, and varying degrees of hearing loss and mental retardation. Previous publications have suggested that it may be difficult to distinguish acrodystostosis from pseudohypoparathyroidism on clinical grounds, but acrodysostosis does appear to have distinct clinical and radiologic findings. Spinal stenosis is an underappreciated risk in acrodysostosis, despite the reported loss of normal caudal widening of the lumbar interpediculate distance on AP spine radiographs in the original report of this disorder by Robinow et al., with confirmation of these radiographic findings by Butler et al. We report two sporadic cases of acrodysostosis, one of which required decompressive laminectomy for symptomatic spinal stenosis, and review 11 cases of acrodysostosis from 9 families that were submitted to the International Skeletal Dysplasia Registry. The objective of this report is to determine the frequency and severity of spinal stenosis in patients with acrodysostosis and to summarize the clinical and radiographic findings of acrodysostosis in an effort to distinguish acrodysostosis clearly from pseudohypoparathyroidism. The pattern of brachydactyly differs between these two conditions, and varying degrees of spinal stenosis are characteristic of acrodysostosis. Both our index patients with acrodysostosis had normal bioactivity of the alpha subunit of the Gs protein, therefore indicating that acrodysostosis has a different pathogenesis from pseudohypoparathyroidism. Furthermore, single-strand confirmational polymorphism (SSCP) analysis failed to demonstrate any confirmational alterations in the coding exons of the Gs alpha gene. These radiographic and laboratory findings substantiate that acrodysostosis is clinically different from pseudohypoparathyroidism and that it is necessary to follow patients with acrodysostosis for signs of spinal stenosis. PMID- 11200994 TI - Schneckenbecken dysplasia, radiology, and histology. AB - To our knowledge this is the first report of Schneckenbecken dysplasia with the development of hydrops early in the second trimester. The radiological findings showed the typical hypoplastic iliac bones with medial extension and very flattened, on lateral view, oval-shaped vertebral bodies and short long bones. The histology showed hypercellular and hypervascular cartilage with chondrocytes with centrally located nucleus. The absence of the lacunar space as described before was also observed in some chondrocytes in our case. This male fetus was the product of consanguineous parents of Mediterranean origin compatible with autosomal recessive inheritance. PMID- 11200993 TI - A new form of spondyloperipheral dysplasia with facial dysmorphism, flattened vertebrae, hypoplastic pelvis, brachydactyly and soft tissue syndactyly. AB - We report the case of a 9-year-old Japanese boy with spondyloperipheral skeletal dysplasia associated with facial dysmorphism, pelvic abnormalities, and distinctive hands and feet. Radiographic manifestations included mild platyspondyly with posterior scalloping, small flared ilia with shallow acetabulae, mesomelic shortening of long bones, marked delay of carpal bone maturation, and brachydactyly with hypoplastic middle and terminal phalanges bilaterally in both hands and feet. There was bilateral soft tissue syndactyly of the 2nd and 3rd interdigital spaces of the hands, the 2nd interdigital space of the feet, with hypoplastic nails. The clinical and radiographic manifestations in this case appear to represent a unique type of skeletal dysplasia. PMID- 11200995 TI - Naumoff short-rib polydactyly syndrome compounded with Mohr oral-facial-digital syndrome. AB - A stillborn baby boy had findings of severe constitutional dwarfism with short limbs, short ribs, and polydactyly that were consistent with Naumoff (type III) short-rib polydactyly syndrome. He also had additional congenital anomalies, including cleft palate, notching of the upper lip, small tongue with accessory sublingual tissue. These oral and pharyngeal anomalies were consistent with Mohr (type II) oral-facial-digital syndrome. We suggest the stillborn infant represented a compound of Naumoff short-rib polydactyly syndrome (SRPS-III) and Mohr oral-facial-digital syndrome (OFDS-II). PMID- 11200996 TI - Cerebro-costo-mandibular syndrome. AB - Cerebro-costo-mandibular syndrome is a rare disorder characterized by rib malformations, various degrees of cerebral maldevelopment, mental deficiency, palatal defects, and micrognatia. This syndrome was first described in 1966. The majority of cases are sporadic, but a few instances of familial occurrence have been reported, some with an autosomal recessive pattern of inheritance. Mortality in early age has been high, probably mostly due to respiratory insufficiency secondary to rib abnormalities and flail chest. We report a mother and son with this disorder, suggesting autosomal dominant transmission. PMID- 11200997 TI - "Duplicate calcaneus": a rare developmental defect observed in several skeletal dysplasias. AB - Duplication of the calcaneus is a rarely observed radiographic finding that probably results from delayed coalescence of two primary calcaneal centers of ossification. We performed a review of 2,500 computerized cases of skeletal dysplasias and syndromes with bone involvement in the International Skeletal Dysplasia Registry, searching for those cases in which a duplicate calcaneus had been recorded. We found that it was a non-random feature of three skeletal dysplasias and groups comprising thanatophoric dysplasia and the chondrodysplasia punctata and short rib (polydactyly) groups. We conclude that duplication of the calcaneus should be considered a consistent feature of these entities and may reflect a more generalized developmental defect. PMID- 11200998 TI - Lethality in Desbuquois dysplasia: three new cases. AB - Three new cases of Desbuquois syndrome in two brothers and a sporadic male, all of whom died in early infancy, are presented to emphasize the high rate (33 %) of lethality in this variable, but serious skeletal dysplasia. Including the three presented patients and 10 of the 36 cases in the literature who died, most did so between birth and 7 months and from respiratory-related problems. Neonatal and infancy survivors should be monitored closely, particularly relative to their pulmonary status. PMID- 11200999 TI - Asynchronous asymmetric form of heterogeneous osteopetrosis: initial case expanded and a new case. AB - We have discovered additional serial radiographs and clinical information on the initial case of "regional osteopetrosis tarda" that has been included in several editions of Caffey's Pediatric X-Ray Diagnosis. A definite second case was found after a search of radiology teaching files of other selected medical centers and the International Skeletal Dysplasia Registry. Analysis of the sequential unusual radiographic findings of the initial case and the equivalent compelling findings of the second case justifies renewed attention to an asynchronous asymmetric form of heterogeneous osteopetrosis. PMID- 11201000 TI - [Recommendations by the Pediatric and Adolescent Rheumatology Study Committee on therapy with Etanercept (p75 TNF-alpha receptor immunoglobulin fusion protein. Pharmacotherapy Committee]. PMID- 11201001 TI - [Underestimated adverse effects of non-steroidal anti-inflammatory drugs on the distal intestine]. AB - NSAID-induced adverse effects are diagnosed less frequently in the distal intestine than in the gastroduodenal area. During long-term NSAID use, however, the development of life-threatening ulcerations, perforations or fibrotic stenoses must be expected from the middle segment of the small intestine to the rectum. Although the clinical symptoms are not specific, together with careful examination, endoscopy, contrast x-ray studies, or computed tomography they can provide orientation, at least with regard to stenotic processes. Diarrhea, weight loss, anorexia, irregular bowel movements, obstruction symptoms, ocoult blood loss, hypoalbuminemia, and iron deficiency may be regarded as possible signs of gastrointestinal adverse effects associated with long-term NSAID therapy. Except in the case of NSAID suppository abuse, no risk indicators are known. The pathogenesis of NSAID-induced adverse effects in the lower gastrointestinal tract has not been elucidated. As the potential of nonselective NSAIDs to cause adverse effects in distal segments of the small intestine cannot be reliably reduced by prophylactic measures in the upper gastrointestinal tract such as comedication with prostaglandin analogs or proton pump inhibitors, the indication for the use of conventional NSAIDs, in any case, must be considered with caution. PMID- 11201002 TI - Plasma oxytocin levels in female fibromyalgia syndrome patients. AB - OBJECTIVES: Fibromyalgia syndrome (FMS) is a chronic pain disorder, where 90% of the patients struck by the disorder are women. The neuropeptide oxytocin is known to have antinociceptive and analgesic, as well as anxiolytic and antidepressant effects, which makes this neuropeptide of interest in fibromyalgia research. The aim of this study was to assess oxytocin concentrations in female FMS patients with different hormonal status and in depressed and non-depressed patients and relate oxytocin concentrations to adverse symptoms as pain, stress, depression, anxiety and to the positive item happiness. METHODS: Thirty-nine patients and 30 controls registered these symptoms daily during 28 days and blood samples for the assessment of oxytocin were drawn twice in all patients and controls. Besides the daily ratings, depression was also estimated with the self-rating instrument Beck Depression Inventory (BDI). RESULTS: Depressed patients according to the BDI differed significantly with low levels of oxytocin compared to the non-depressed patients and the controls. Low levels of oxytocin were also seen in high scoring pain, stress and depression patients according to the daily ratings; however, these subgroups were small. A negative correlation was found between the scored symptoms depression and anxiety and oxytocin concentration, and a positive correlation between the item happiness and oxytocin. The oxytocin concentration did not differ between the hormonally different subgroups of patients or controls. CONCLUSION: The results suggest that the neuropeptide oxytocin may, together with other neuropeptides and neurotransmitters, play a role in the integration of the stress axes, monoaminergic systems and the pain processing peptides in the pathophysiologic mechanisms responsible for the symptoms in the FMS. PMID- 11201003 TI - [Functional changes in the quadriceps femoris muscle in patients with varus gonarthrosis]. AB - In osteoarthritis (OA) of the knee, arthrogenous muscle inhibition (AMI) is considered to be one of the reasons of quadricep muscle weakness. Its influence on functional impairment such as gait alterations, however, still remains unclear. Fourty-seven patients with knee OA (mean age 64 +/- 5.2 years, 36 women, 11 men) and 47 age- and gender-matched healthy controls were investigated for voluntary activation (VA) and maximum voluntary contraction (MVC) of the quadricep muscle. In addition, these two parameters of AMI have been correlated with the extent of gait alterations. Measurement of VA and MVC were performed by a twitch interpolation technique; for gait analysis an optoelectronic motion analysis system (ELITE, Italy) was used. Quadricep MVC and VA were significantly lower in OA than in control knees. Moreover, in addition to reduced walking velocity and step cadence, gait analysis revealed significantly lower stance phase re-extension angles in OA patients (mean 2.7 degrees +/- 2.6) than in control knees (mean 10.7 degrees +/- 4.9). Hereby, in OA knees there was a significant correlation between MVC and VA deficits and the reduction of re extension angles. The work shows that knee OA is characterized by severe alterations of the quadricep motor function due to arthrogenous muscle inhibition. Hereby, quadricep AMI represents one major reason for functional impairment in knee OA. PMID- 11201004 TI - How to proceed in patients with carcinoma detected after laparoscopic cholecystectomy. AB - Carcinoma of the gallbladder is a rare disease. Gallbladder carcinoma is detected in less than 1% of all gallstone operations. With the introduction of laparoscopic surgery and the higher acceptance of this technique, gallbladders are now removed much earlier than they used to be. With the increase of cholecystectomies, the diagnosis of unexpected gallbladder carcinoma became more frequent. We report on how to proceed in patients with a diagnosis of gallbladder carcinoma and discuss the additional problems that have arisen since laparoscopic cholecystectomy became established. From June 1990 to December 1999, we performed 6230 cholecystectomies in the surgical department of Moabit Hospital in Berlin. Of these, 42 (0.6%) were identified as carcinoma. There were 37 women and five men, and the mean age was 69 years. In 16 patients (39%), there was a preoperative suspicion of malignancy. In 26 patients (61%), malignancy was suspected intraoperatively or diagnosed postoperatively after pathologic examination of the resected gallbladder. In these patients, an open repeat operation was necessary in seven cases to achieve an adequate curative resection and staging. This involved additional liver bed resection and lymph node dissection of the hepatoduodenal ligament. Abdominal wall (port site) recurrence in the absence of distant metastasis was present only in two patients. We recommend removal using a bag in all gallbladders with wall thickening, irregularities, or scleroatrophic calcified gallbladder area. In stage Tis or T1, laparoscopic cholecystectomy is sufficient. In stage T2 and T3, we perform a repeat operation with liver bed resection and lymphadenectomy. PMID- 11201005 TI - Gallbladder carcinoma and surgical treatment. AB - Gallbladder carcinoma shows an unusual geographic and demographic distribution. It is relatively uncommon in Europe, but more frequent in Israel, Chile, Bolivia and in Southwestern Native Americans in the United States. Chronic cholecystitis, choledochal cysts, high body mass index, female gender, age, nicotine and industrial exposure to carcinogens are associated risk factors. The frequency of gallbladder cancer in all operations of the biliary tract is about 1-3%, reflecting the commonest biliary tract malignancy. Preoperative imaging, including ultrasound and computed tomography (CT), may reveal signs indicative of the presence of malignancy. However, most patients are not diagnosed prior to surgical intervention. Survival depends on the ability to achieve a curative resection, including hepatectomy and lymph node dissection in patients with local extended tumour according to the stage of the disease. Overall, the curative resection rates for gallbladder carcinoma range from 10% to 30%. Regional and para-aortic lymphadenectomy provides no survival benefit for patients with para aortic disease, which has a negative influence on prognosis equivalent to that of distant metastases. A survival benefit is seen only in selected patients with metastases limited to the regional nodes. Taking a sample biopsy of the para aortic nodes before starting surgery is recommended because these nodes are involved more frequently than expected. For those patients with unresectable cancer, palliative surgical, endoscopic or radiological bypass procedures can improve quality of life. Other approaches to the management of advanced tumours include systemic chemotherapy or combined chemo-radiotherapy and need further evaluation. Early-stage tumours are often discovered as an incidental finding during (laparoscopic) cholecystectomy or on histological examination of the gallbladder, mostly necessitating relaparotomy and extensive resection. In the following, management of patients with gallbladder cancer at different stages and situations is discussed. PMID- 11201006 TI - Appraisal of surgical resection of gallbladder cancer with special reference to lymph node dissection. AB - BACKGROUND: Radical lymph node dissection in surgery for advanced gallbladder cancer is controversial. The purpose of this study is to evaluate the role of lymph node dissection based on the clinico-pathologic results. PATIENTS: Seventy three patients who underwent radical surgery including systematic dissection of the N1+N2 region lymph node plus some of the para-aortic nodes were reviewed. RESULTS: pT1 patients had no lymph node metastasis, but pT2 and pT3/pT4 patients had lymph node metastasis at a rate of 50.0% (13/26) and 83.3% (25/30), respectively. As infiltration of the hepatoduodenal ligament (Binf) became severe, the rate and extent of lymph node metastasis increased. There were four 5 year survivors with lymph node involvement. The 5-year survival rates are 77.0% in pN0 cases and 27.3% in pN1 cases (P<0.01). There was no difference in survival between pN1 and pN2 patients. However, significant differences in survival were observed between pN0/1 and pN2/3 patients when these patients were limited to Binf0/1. Examination of the recurrence pattern showed that most patients with pN0/1/2 had no regional lymph node recurrence, but there was para-aortic lymph node recurrence in patients with pN3 outside the dissected region. Significant prognostic factors influencing survival after surgery by multivariate analysis were pN2/3, pT, and residual tumor. CONCLUSION: Systematic lymph node dissection of N1, N2, and part of the para-aortic region improves survival in advanced gallbladder cancer patients, especially in those without either para-aortic lymph node metastases or Binf2/3. PMID- 11201007 TI - Primary hyperparathyroidism--early diagnosis in patients referred for thyroid surgery. AB - BACKGROUND AND AIMS: From 1986 to 1998, 190 patients presented for first-time operations for sporadic, non-malignant, non-multiple endocrine neplasia primary hyperparathyroidism. Of these patients, 54% had been classified as "asymptomatic", 41% as symptomatic and 5% as acute. One hundred and thirty-five patients (71%) were referred to us for parathyroid surgery. Fifty-five patients (29%) were referred for thyroid surgery with hitherto unknown hyperparathyroidism. This corresponds to a prevalence of primary hyperparathyroidism of 1% in patients referred for thyroid surgery (5450 patients during the same period of time). PATIENTS/METHODS: Patients referred for parathyroid surgery (group I, n=135) were compared with patients originally referred for thyroid surgery (group II, n=55). Group II was divided into group IIa: hyperparathyroidism preoperatively biochemically evident (n=26), and group IIb: borderline biochemistry, parathyroid enlargement evident at the operation (n=29). The groups were compared regarding clinical manifestations, serum calcium and parathyroid hormone, pathologic-anatomical substrates, operative complications and outcome. RESULTS: Renal, osseous and gastrointestinal manifestations were more frequent in group I than in groups IIa and IIb (P<0.05). However, cardiovascular and neuromuscular symptoms were present in groups IIa and IIb in more than one-third of patients. Patients from group IIb were younger (49+/-12 years) than patients from groups IIa (60+/-13 years) and I (60+/-14 years). Adenomas were found in 85% of group I patients, in 45% of group IIa patients and in 21% of group IIb patients (P<0.01). In all other cases, hyperplasia was confirmed histologically. Serum calcium was higher in group I (3.0+/-0.42 mmol/l) than in groups IIa (2.63+/-0.16 mmol/l) and IIb (2.46+/-0.14 mmol/l) (P<0.01). Serum PTH was higher in group I (median 11.0 pmol/l) than in groups IIa and IIb (median 7.1 and 6.4 pmol/l, respectively) (P<0.05). Postoperatively, hypercalcemia persisted in two patients (1.1%) belonging to group I, with mediastinal adenomas. Serum calcium at discharge showed no differences between groups (group I: 2.22+/-0.16; group IIa: 2.22+/-0.15; group IIb: 2.20+/-0.11 mmol/l). Recurrent laryngeal nerve paralysis occurred early (4.2% of "nerves at risk") and remained permanent (0.8% of "nerves at risk") without significant differences between groups. CONCLUSION: Diagnostic efforts regarding parathyroid function should be mandatory before thyroid operations. "Asymptomatic" patients frequently (more than 30%) present with cardiovascular and neuromuscular, "unspecific" symptoms. Simultaneous parathyroid exploration is obvious in cases with biochemically evident primary hyperparathyroidism, but should also be performed in patients with borderline biochemistry. PMID- 11201008 TI - Benign solitary fibrous tumour of the thigh: morphological, chromosomal and differential diagnostic aspects. AB - Solitary fibrous tumours (SFTs) are rare and usually benign neoplasms of mesenchymal origin that are often found in the visceral pleura (fibrous pleural tumour, FPT) or other serosal surfaces. They have also been found in soft tissues. We report the case of an SFT localised in the thigh of an 86-year-old woman. The tumour specimen was examined morphologically, immunohistochemically and molecular genetically, using comparative genomic hybridisation (CGH). The latter detects unbalanced chromosomal alterations in human neoplasms by competitive nucleic acid hybridisation and consecutive computer image analysis. The tumour consists of fibroblast-like cells, arranged in a typical "patternless pattern". Immunohistochemically, the tumour stained positively for vimentin, CD34, CD99, and focally for actin and desmin. No reaction occurred with keratin or S100 protein antibodies. CGH detected a single loss on chromosome 13q. PMID- 11201009 TI - Surgical treatment of postoperative, incidentally diagnosed small sporadic C-cell carcinomas of the thyroid. AB - BACKGROUND AND AIMS: The surgical strategy in small sporadic C-cell carcinomas of the thyroid that are incidentally diagnosed after goiter resection for benign disease is controversial. It remains unclear whether a completion thyroidectomy should be performed in every case. PATIENTS AND METHODS: We present nine patients who were operated on between October 1992 and October 1997 in whom an unexpected, small sporadic C-cell carcinoma (seven with pT1, two with pT2) was found in the postoperative histology. RESULTS: All patients were calcitonin negative and there were no signs of the disease being inherited (no familial history, negative RET proto-oncogene). No patient underwent a completion thyroidectomy. All patients had a follow-up with pentagastrin-stimulated calcitonin and carcinoembryonic antigen (CEA) 3 months, 6 months and annually after the operation. No patient became calcitonin positive or showed any other signs of tumor recurrence after a follow-up period of 2-7 years. CONCLUSION: A completion thyroidectomy is not necessary in small sporadic C-cell carcinoma that is incidentally diagnosed after resection for benign disease if there is no sign of familial cancer and if calcitonin is negative. A close follow-up is necessary. PMID- 11201010 TI - Postischemic cardiac function recovery in the isolated rat heart: effects of adenosine deaminase and nucleoside transport inhibition. AB - BACKGROUND AND AIMS: This study assessed the cardioprotective effects of inhibitors of adenosine metabolism in an isolated perfused rat heart model. Specifically, we studied the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3 nonyl)-adenine and the selective nucleoside transport inhibitor S-(p-nitrobenzyl) 6-thioinosine, in terms of their potential to enhance protection when added to Bretschneider's cardioplegic solution. METHODS: Rat hearts were infused for 5 min with Krebs-Henseleit buffer solution (group 1), Bretschneider's cardioplegic solution (group 2), Bretschneider's cardioplegic solution with the addition of 25 microM erythro-9-(2-hydroxy-3-nonyl)-adenine and 5 microM S-(p-nitrobenzyl)-6 thioinosine (group 3), and Bretschneider's cardioplegic solution with the addtion of 25 microM erythro-9-(2-hydroxy-3-nonyl)-adenine only (group 4). After cardioplegic arrest and 45 min of ischemic storage at 25 degrees C, the functional recovery of the hearts was tested during 15 min of Langendorff reperfusion and then 45 min of working heart reperfusion. RESULTS: In relation to the cardioprotective effects of Bretschneider's cardioplegic solution alone, we observed an improved recovery of hemodynamic function of the hearts with the addition of both erythro-9-(2-hydroxy-3-nonyl)-adenine and S-(p-nitrobenzyl)-6 thioinosine. However, the myocardial adenosine triphosphate (ATP) concentration remained unchanged. Bradycardia observed under the addition of erythro-9-(2 hydroxy-3-nonyl)-adenine alone was prevented by the addition of S-(p-nitrobenzyl) 6-thioinosine. CONCLUSION: A combination of both substances may be tested further for cardiac preservation, as it might improve the recovery from ischemia at moderate temperatures. PMID- 11201011 TI - [Interventional gerontology from the medical, institutional and social policy viewpoint]. PMID- 11201013 TI - The role of ACE inhibitors in the treatment of hypertensive elderly patients. AB - Hypertension has a high prevalence among elderly patients. Randomised trials have already demonstrated that treating healthy older persons with hypertension is highly efficacious. Nevertheless some questions have arisen. On the one hand the generalizability of these trial results, particularly for older persons with serious medical comorbidities and poor functional status, is not clear. On the other hand different antihypertensive drugs have shown to be effective. Which drug for which patient? Even data from randomised intervention trials showing that the treatment affects cardiovascular morbidity and mortality, were missing, ACE inhibitors have been used for more than a decade to treat high blood pressure. For a younger population the captopril prevention project showed no differences between ACE inhibitors and conventional antihypertensive treatment (diuretics, beta-blocker) concerning the primary endpoints (myocardial infarction, stroke and other cardiovascular death). The STOP-2 study also confirmed these results for elderly patients. When treating elderly patients one must be aware of physiological changes with age and the comorbidities. Of significance among this patient group is declining renal function. Admissions for uraemia that are related to the use of ACE inhibitors are still commonplace, although many cases are preventable by monitoring renal function, but guidelines are still missing. Concerning the comorbidities ACE inhibitors have benefits compared to other antihypertensive drugs, especially in cases of heart failure, diabetes and coronary heart disease. PMID- 11201012 TI - Treatment of arterial hypertension with diuretics, beta- and calcium channel blockers in old patients. AB - Hypertension increases in prevalence with age. Population based studies suggest that more than 50% of people over the age of 65 years may have chronic hypertension. Hypertension, especially systolic hypertension, is the single most common, powerful, however, treatable risk factor for cardiovascular morbidity and mortality in the elderly. In order to assess the effectiveness of antihypertensive drug therapy among the elderly, with diuretics, beta-blockers and calcium channel blockers, a literature search was performed at the Cochrane Library, Medline and Excerpta medica. The Cochrane Hypertension Group identified 14 randomised controlled trials of at least one year duration with 21,785 elderly subjects where diuretics, beta-blockers or calcium channel blockers were used in the treatment group as first line drugs. In their meta-analysis (including one small trial with a central acting antiadrenergic drug) there was a decrease in total mortality (111 vs 129 deaths) and cardiovascular morbidity and mortality (126 vs 177 events) within the treatment group. The three trials restricted to persons with isolated systolic hypertension indicated beneficial effects in the treatment group with regard to cardiovascular morbidity and mortality (104 vs 157 events). Trial data on adverse effects is limited. In three studies, where adverse effects were reported, no substantial differences between treatment and control groups in measures of physical, cognitive and emotional function were found. Cardiovascular benefits of treatment with low dose diuretics or beta blockers are cleared for elderly subjects with either diastolic or isolated systolic hypertension. Treatment with a long-acting dihydropyridine calcium channel blocker shows beneficial effects in reducing cardiovascular morbidity and mortality for elderly people with isolated systolic hypertension. Due to inconsistent findings in a subgroup meta-analysis of antihypertensive drug treatment in very old people, the efficacy of antihypertensive treatment in these subjects still remains unclear. PMID- 11201014 TI - [Aortic valve replacement in 80- and over 80-year-old patients. Short-term and long-term results]. AB - Due to demographic changes in average life expectancy, the age of patients undergoing cardiac surgery is increasing as well. We have reviewed the short- and long-term outcome in patients over 80 years of age after aortic valve replacement. From 01 Jan 1995 until 31 Dec 1998, 105 patients (76 women, 29 men between 80 and 89 years, median: 83) underwent aortic valve replacement. 42% presented with aortic stenosis, 58% with combined valve disease with leading stenosis. 53% (group A) received isolated valve replacement, 47% (group B) underwent myocardial revascularization as well. The in-hospital mortality rate was 8.9% for group A and 14.3% for group B. The follow-up time ranged between 10 and 243 weeks (median: 112 weeks). None of the patients had to be reoperated for prosthetic valve dysfunction or endocarditis. Bleeding complications due to anticoagulant therapy were not observed. Of the 11 deaths during the follow-up period, 5 (45%) were cardiac in nature and 2 (18%) related to stroke. Actuarial survival rates for group A were 98, 95 and 88% at 1, 2 and 3 years, and for group B 92, 84 and 84%, respectively. Permanent nursing care was not required 1 year after the operation by 98% of patients in group A (2 years: 95%, 3 years: 88%) and by 100% of patients in group B (2 years: 95%, 3 years: 88%). At an interval of 1 year after the operation 98% of patients in group A had not been hospitalized as a result of cardiac disorders (2 years: 98%, 3 years: 94%). The rates for group B were 90, 82 and 82%. Compared with younger age groups, aortic valve replacement in patients 80 years of age and older is associated with a distinctly increased mortality and morbidity. However, our data suggest that considering the poor prognosis of conservative therapy of symptomatic aortic valve disease, the functional status as well as life expectancy in this age group seems to be positively influenced by aortic valve replacement. PMID- 11201015 TI - [Therapy of fecal incontinence in elderly patients: Study of a home biofeedback training program]. AB - The increased prevalence of urinary and fecal incontinence is one of the most important factors in the loss of independence and mobility in the elderly population. It is also one of the major reasons for elderly people to give up their household and move into a nursing home. Anorectal biofeedback therapy is a very effective treatment for fecal incontinence. However, due to the increased immobility of elderly people, ambulatory biofeedback training programs which require the participants to leave their homes and travel to the next available outpatient clinic on a regular basis, especially when depending on public transportation, may prove particularly difficult for elderly, incontinent subjects. Supervised home biofeedback training programs may offer an alternative for those patients, who are motivated enough and not mentally impaired. Two different age groups of women (between 49 and 63; and between 65 and 78 years old) suffering from fecal incontinence due to external anal sphincter impairment, received a supervised home biofeedback program, after extensive anorectal diagnostics including manometry. The program focused on improving voluntary sphincter contraction. After an average of 9 months, anorectal manometry was repeated, and anal resting and squeeze pressure as well as minimal rectal perception threshold were determined. There was no effect on anal resting pressure and rectal perception. However, anal maximum squeeze pressure as well as squeeze pressure over 10 s was substantially increased with no difference between the age groups. CONCLUSION: Supervised home biofeedback for sphincter insufficiency was effective in improving the voluntary contraction of the anorectum in both age groups. Therefore, biofeedback home training programs may offer an alternative to ambulatory programs for those individuals, who are not mobile enough to regularly attend an outpatient clinic. PMID- 11201016 TI - [Senior studies at the Mannheim University in the opinion of the faculty]. AB - For over 15 years now, the University of Mannheim has offered studies for senior citizens, which are conceived as an integration model. The older students take regular courses together with the young students. Former surveys showed large satisfaction of the older students with this model. As a check of these results, 69 university teachers, who have older students in their classes, were asked about their experiences and their opinion on the senior citizens' studies by usage of a questionnaire which has been developed by Kolland for a similar purpose. Predominantly positive experiences are mentioned. The older students are seen as an enrichment rather than as a burden. Conflicts and difficulties have hardly appeared. The majority deny differences between older and younger students. A differential examination points out that older teaching staff have a more favorable opinion of senior citizens' studies than the younger ones. It is also pointed out that representatives of humanistic subjects have a more positive view of the older students than representatives of the empirical mathematical field. However, more research is needed in this area. PMID- 11201018 TI - [Reality of geriatric psychiatry services in a large West German city]. AB - A comprehensive survey of psychogeriatric services was carried out as a part of public health planning in Solingen, a city of 165,000 inhabitants. The investigations consisted of extensive questionnaires and numerous interviews. Mental disorders are suspected in 15-20% of general practitioner's patients, in 62% of community health care center clients and in 65.5% of the residents of geriatric nursing homes and old people's homes. Hardly half of the latter and less than 20% of the clients of community health care center are under psychiatric treatment. Psychiatrists reach only about half as many elderly persons as must be expected from epidemiological data; the rate of clinical psychogeriatric treatment is lower than in some other German regions. The extend of psychotherapy in old age is very low. Collaboration between general practitioners and psychiatrists should be improved; in institutions training and supervision are deficient. PMID- 11201017 TI - [Aggressive and auto-aggressive behavior of acute geriatric psychiatry admissions -an empirical contribution]. AB - We investigated the extent of aggressiveness of 494 psychiatric patients at the time of admission. This group was divided into two subgroups according to age: 58 patients were more than 65 years old and the remaining 436 patients were less than 65 years old. The two groups were similar as far as kind and frequency of aggressive behaviour against self or others at the time of admission were concerned. There was an important difference in handling the aggressive behaviour as this was significantly easier with the older patients. Furthermore it was possible to describe psychopathological profiles of risk for both allo- and autoaggressive behaviour. Sociodemographic factors could be identified which were linked with the extent of aggressive behaviour by calculating odds ratios. PMID- 11201019 TI - [Developoment of qualifications in German nursing care--results of current data analysis]. AB - Nursing provides a service catering to the needs of the individual and, as such, makes its own contribution towards community health care. Apart from organizational and instrumental determinants, manpower resources are of central significance in this context. The number of staff employed in nursing, their qualifications and competences are all factors which fundamentally influence the quality and efficiency of nursing care. Based on current data, the following article will first describe which manpower resources are available in the individual nursing sectors. It will then articulate as a central theme some of the main problems in professional training at the various levels (general, advanced and further education), including Germany's comparatively new university and college degrees in nursing. The results of our analysis indicate, on the one hand, that there is movement towards an improved professional profile in nursing, which could be classified as optimizing manpower resources. For example, far more than two thirds of all nursing staff and other care workers have completed three year professional training courses. In addition, nursing trainees overproportionately graduate from junior levels of secondary schools. It may, furthermore, be noted that nursing continues to be in high demand as a vocational profession and that there has been a professional upgrade in particular at the teaching and leadership levels. On the other hand, however, we can make out anti professional developments which contribute to an impairment of manpower resources in nursing. A comparison of 1996 and 1999 figures shows that the number of qualified staff in the care of the elderly has decreased whereas the number of untrained staff has increased by six times. In spite of heavier work loads there has been no increase in the number of staff and trainees in hospital nursing over the past few years. And, with the introduction of statutory insurance covering ongoing nursing care, various semi-professional trainee programs have emerged, leading to a partial displacement of qualified staff. In conclusion, the authors will reflect on how to overcome such developments and further optimize manpower resources in nursing. PMID- 11201020 TI - [Are psychiatric illnesses adequately considered in distribution of nursing care levels according to the nursing care insurance law? Evaluation using a new scale for evaluating need for nursing care by senior citizens]. AB - The object of our study is the evaluation of care needs of senior citizens and the adjustment of certain stage of care according to the German Health Care Act ("Pflegeversicherungsgesetz"). For assessment of care needs we developed a new rating scale (BPS). Factor analysis of the rating scale showed 5 dimensions: (1) "Psychoorganic Syndrome" (Dementia), (2) "Physical Care Needs", (3) "Lack of Social Skills", (4) "Aggressiveness" and (5) "Depression". The sample size is N = 1739, mean age 82.5 years. A statistically significant partial correlation of the extent of care needs as indicated by the stage of care described by BPS dimensions was found only for dimension (2) "Physical Care Needs" (r = 0.50). Cluster analysis resulted in distribution of the whole sample into 6 discriminable groups, according to their syndrome specificity (BPS profiles). Additionally clusters are different regarding the severity of need for care. It is obvious, analyzing the adjustment of stages of care within clusters, that psychiatric relevant disturbances contribute substantially to this adjustment. Nevertheless this finding is valid only for aged people, who receive regular care by ambulant or home services, and can not be transferred to senior citizens cared by their families. PMID- 11201021 TI - Coexistence of factor V Leiden and primary antiphospholipid syndrome: a patient with recurrent myocardial infarctions and thrombocytopenia. AB - Increased thrombin generation associated with resistance to activated protein C makes the latter a likely candidate for an increased risk of acute coronary events. Activated protein C resistance (factor V Leiden) on its own, however, appears to have no significant effect in this regard. We describe a case of recurrent myocardial infarction caused by coronary thrombosis in a patient with persistent thrombocytopenia who was found to have a coexistence of heterozygous factor V Leiden and primary antiphospholipid syndrome. Since both thrombophilic disorders interfere with the protein C anticoagulant system, the simultaneous existence of inherited and acquired resistance against activated protein C could account for an increased thrombophilia with manifestation in the coronary arteries. This case suggests that evaluation of patients who present with recurrent acute coronary events should also consider these coagulation defects. PMID- 11201023 TI - [Intravenous long-term thrombolysis of an occluded aortocoronary venous bypass graft]. AB - A 41-year-old man presented with progressive unstable angina pectoris during the last three hours. At admission the electrocardiogram and cardiac specific enzymes showed no signs of ischemia. During the next 24 hours the electrocardiogram and cardiac enzymes developed signs of a non-Q-wave anterolateral infarction. The patient had known coronary artery disease and underwent aortocoronary bypass surgery seven years ago. Coronary angiography after admission revealed a chronically occluded vein graft to the right coronary artery (RCA) and a subtotal occlusion of the vein graft to the left anterior descending artery (LAD) with a TIMI flow 0-I. Because of unfavorable results of mechanical revascularization of occluded bypass grafts and high risk of catheter dislocation and bleeding complications of intracoronary local thrombolysis, the patient subsequently received intravenous long-term thrombolysis for 24 hours. After successful lysis of the thrombus the bypass graft to the LAD showed two severe stenoses but blood flow has returned to normal. Three days later percutaneous transluminal coronary angioplasty (PTCA) and stent implantation were carried out with a good primary angiographic result. After 6 months the patient was still asymptomatic and a treadmill exercise test showed no signs of ischemia. PMID- 11201022 TI - [New antithrombotic therapy approaches in coronary heart disease--prospects for gene therapy]. AB - Despite considerable progress, pharmacological therapies have not provided a complete solution for common cardiovascular problems, including recurrent thrombosis, restenosis, and vein graft deterioration. Optimal drug dosage, reproducing plasma concentrations achieved in animal studies establishing proof of-principle, would often be too toxic to administer. Local gene therapy aims at overexpressing proteins that regulate the cell cycle of vascular smooth muscle cells, inhibit vascular smooth muscle cell migration, endow the endothelium with enhanced vasoprotective properties. Alternatively, some approaches tend to suppress gene expression of proteins believed to promote vascular smooth muscle cell proliferation and migration. In sharp contrast to drug treatments, local gene therapy limits expression of the beneficial agent to the injured vascular site, where it can extend the presence of this agent to weeks and, with some gene vectors, to many months. This review summarizes and discusses antithrombotic gene therapy approaches for the prevention of restenosis and late thrombosis after catheter-based revascularizations. PMID- 11201024 TI - [Neurological events in patients with atrial fibrillation: outcome and preventive practices]. AB - BACKGROUND: Atrial fibrillation (AF) is associated with neurologic events (transient ischemic attack (TIA) and stroke). The objective of the present study was to determine the outcome of patients with neurological events and atrial fibrillation (AF) in comparison with patients in sinus rhythm (SR), and to investigate the primary and secondary prevention practices in patients with neurological events and AF. PATIENTS AND METHODS: In a prospective, observational, single center study in a large public, university-affiliated hospital all patients admitted between 1/97 and 1/98 with acute neurologic events were registered (n = 369). The association between outcome of neurologic events as assessed by survival status, functional status (Rankin scale) and severity of event (European Stroke Scale) and heart rhythm was investigated by use of logistic regression. Antithrombotic medication on admission and at discharge was recorded. RESULTS: The mean age of the 369 patients was 75.1 +/- 10.9 years; 56.1% were female. A TIA was present in 26.2% and stroke in 73.8%. 287 patients (77.8%) were in SR and 82 in AF on admission (22.2%). In-hospital mortality was 12.7% in all patients. In patients with AF, mortality was 23.2% and 9.8% in patients with SR (p = 0.0013). Patients with AF were significantly older than patients with SR (80.4 +/- 7.5 versus 73.5 +/- 11.2 years; p < 0.001). Multivariate analysis identified heart rhythm as an independent predictor of survival (p < 0.01). Patients with AF did suffer from a more severe neurological deficit on admission and at discharge than patients with SR. In 46.3% of patients with AF severe dependency was present (Rankin 4/5), while this was the case in 28.5% of patients with SR (p < 0.01). The ESS score of patients with AF was 77.4 +/- 30.6 at discharge compared to 88.1 +/- 20.3 in patients with SR (p < 0.01). In 50 of 82 patients (61%) AF was previously known. Of these 50 patients 36% did not receive any kind of antithrombotic treatment and only 12% were receiving oral anticoagulants before the event. Of 63 surviving patients with AF 32 did not have any contraindications against anticoagulation treatment. At discharge, 14 (43.8%) of these patients were receiving oral anticoagulants, 17 aspirin or ticlopidine (53.1%) and 1 patient (3.1%) no type of antithrombotic medication. CONCLUSIONS: Neurologic events in patients with AF are more severe and outcome is significantly poorer than in patients with SR. Anticoagulation as the effective therapy for primary and secondary prevention of neurologic events is seriously underused in daily practice. PMID- 11201025 TI - [Mechanism of induction and termination of ventricular fibrillation--significance of dispersion of ventricular repolarization]. AB - It has been known for many years that ventricular fibrillation may be induced and terminated by electrical field stimuli. Recent experimental studies have shown that both fibrillation and defibrillation have a common electrophysiologic mechanism that is based on the interaction between the electrical field stimulus and ventricular repolarization. Ventricular fibrillation will be induced if the field stimulus is applied with the area of vulnerability, this area of vulnerability is defined two dimensionally by the shock coupling interval and shock strength, and is modified by the configuration of the shock. A field shock that is applied within the area of vulnerability causes heterogeneity of ventricular repolarization immediately after the shock (postshock dispersion), thereby enabling the development of circuit movements and reentry, and resulting in ventricular fibrillation. High energy shocks, however, that are applied above the area of vulnerability (i.e., above the upper limit of vulnerability) will not induce ventricular fibrillation due to homogeneous prolongation of repolarization and a resulting small postshock dispersion. In analogy, ventricular fibrillation will continue after unsuccessful low-energy defibrillation shocks due to high postshock dispersion, whereas a high-energy shock will synchronize ventricular repolarization, thereby causing small postshock dispersion and termination of ventricular fibrillation. This paper describes the relation between fibrillation, defibrillation and ventricular repolarization based on experimental findings. A possible clinical application of these findings is that the upper limit of vulnerability may be used as a surrogate for the defibrillation threshold. Thus, defibrillation threshold testing may not be necessary during future implantations of automatic cardioverter defibrillators. PMID- 11201026 TI - [Cardiac arrhythmias in targeted connexin deficient mice: significance for the arrhythmia field]. AB - Intercellular communication can be mediated by gap junction channels. One channel is composed of two hexameric hemichannels which consist of six polypeptide subunits called connexines (Cx). Three different connexines were documented in the cardiac myocytes: Cx40, Cx43 and Cx45. The labeling by number represents the rounded, molecular mass of the amino acid sequences given in kD. Identical connexons form homotypic channels different connexons can form heterotypic channels. Each channel type has specific properties regarding permeability and electrical conductance. Beside a typical age-dependent alignment of gap junction channels on the surface of the cardiac myocytes, regional distribution of the different connexins is different at distinct parts of the mouse heart. The ventricular working myocardium is characterized by Cx43, whereas Cx40 and Cx45 were not found in this region. In the atria as well as in the conduction system, Cx40 is the most frequently expressed. Cx45 appears to form a border zone between conductive and the surrounding working myocardium. In line with the localization and the conduction properties of distinct homotypic gap junction channels, the Cx43 deficient mouse is suitable for analysis of ventricular arrhythmias and the Cx40 deficient mouse primarily for studies of atrial arrhythmias. Increased ventricular conduction velocity and increased ventricular vulnerability were observed in the presence of a decreased number and density of Cx43 gap junction channels. This observation, however, is controversially discussed. Cx40 deficiency induces an impairment of the sinuatrial, intraatrial and atrioventricular conduction properties and is associated with an increased atrial vulnerability. Transgenic mouse models and new mapping techniques for detection of the electrical wavefront propagation provide new insights into the mechanisms of arrhythmogenesis. Geneticists, clinicians and basic researchers need to collaborate in order to explore the clinical relevance of the new mouse models and their use for molecular medicine. PMID- 11201027 TI - [Interventional occlusion of atrial septum defects larter than 20 mm in diameter]. AB - Over the last few years, various devices for the interventional closure of atrial septal defects (ASD) up to a diameter of 20 mm have been developed. We report our clinical experience in closing ASD with a diameter larger than 20 mm diameter with the Amplatzer Septal Occluder (ASO). METHOD: The stretched diameter of the ASD was measured by inflating a sizing balloon within the defect until an indentation in the circumference in the balloon could be observed. An ASO with a stent diameter 2-4 mm larger than the indentation in the circumference of the balloon was chosen and implanted via 9-12 French sheaths. In contrast to the closure of smaller defects, pullback of the device onto the atrial septum was only performed when the connecting stent of the ASO was completely deployed in order to achieve maximal centering characteristics and optimal support of the retention skirt of the left atrial disc on the edges of the defect. Only then was the right atrial disc deployed and actively configured by advancing the sheath and the delivery cable against the atrial septum. Implantation was only attempted if the atrial septal rims (except the anterior rim around the aorta) measured more than 7 mm by echocardiography to avoid injury or disturbance of sensitive intracardiac structures. After placement, the fixation of the device and the mechanical stability was proven by an extensive "Minnesota wiggle". The ASO was released only when TEE showed no or a trivial residual color flow through the connecting stent; otherwise repositioning was performed. RESULTS: Out of 352 patients (P) with successful closure of interatrial defects, 70 P (age: 1.1-77.3 years) had stretched defects larger than 20 mm diameter (median 22 mm diameter (20-36), 25/75% quartiles = 20/26 mm). Mean shunt size was Qp:Qs 2.1:1 (0.7 3.9:1), mean fluoroscopy time 10.9 min (0-63). Complete closure could be achieved in 85.7/93.1/100% after 3 months, 1 and 2 years, respectively. Besides 3 P with persistent atrial fibrillation, only 5 P showed transient atrial tachyarrhythmias, 2 only periprocedural and 3 within the first 3 months after implantation were treated with beta-blocker. In one patient, an acute embolization of the device occurred because a diminished posterior rim was not visualized by a monoplane TEE probe necessitating surgical explantation and defect occlusion. Despite oversizing the device, no "mushrooming" misconfiguration were observed. CONCLUSION: Transcatheter closure of large atrial septal defects with the Amplatzer Septal Occluder is feasible, safe and effective. Risk of complications do not seem to occur more frequently than after closure of smaller defects if one adheres to certain sizing and implantation measures. The incidence of transient atrial tachyarrhythmias seems to be low. PMID- 11201028 TI - [Interventional treatment of congenital heart defects in infants with a body weight up to 2,500 grams]. AB - BACKGROUND: Pediatricians and neonatologists are still reluctant to consider invasive cardiological or cardiosurgical treatment in low body weight infants because it is believed to considerably increase the risk. The aim of this study was to assess the results and complications of percutaneous transcatheter interventions in infants with a weight below 2.5 kilograms. METHODS: Retrospective analysis was undertaken for all patients with a weight below 2.5 kilograms who underwent cardiac catheterization from 01/1994 to 04/1999. During this time 42 diagnostic catheterizations in 29 patients and 27 transcatheter interventions in 24 patients were performed. RESULTS: Surgery was replaced or effectively postponed in 9 (33%) out of 27 transcatheter interventions. This was possible for pulmonary stenosis, valvular aortic stenosis and aortic coarctation. A stabilization of the hemodynamic situation was possible in 14 patients. An antegrade pulmonary flow was established in 5, an effective interatrial shunt created in 5 and the arterial duct stented in 3 patients. Only 3 patients had no benefit from the intervention; however, there were no deaths nor hemodynamic complications. Arrhythmias occurred in 9% of all catheterizations and interventions but were transient in all cases. Femoral arterial complications were observed in 30% of all arterial catheterizations. CONCLUSION: Diagnostic cardiac catheterization and percutaneous transcatheter interventions can be performed with low mortality and acceptable morbidity in low weight infnats. Transcatheter interventions can replace surgery, postpone the necessity for surgery or stabilize the hemodynamic situation prior to surgery. PMID- 11201029 TI - [Atrial natriuretic peptide as an indicator of mild postoperative cardiac dysfunction after uncomplicated bypass surgery]. AB - Plasma levels of ANP (pg/ml; radioimmunoassay) as a parameter for postischemic dysfunction and levels of Troponin T (TnT) (ng/ml; ELISA test) as a parameter for postischemic cellular damage were determined in 15 patients with coronary artery disease (CAD) (mean age: 58 +/- 6.1 years; 13 m, 2 w; with no history of myocardial infarction and no signs for congestive heart failure) prior to, during and after extracorporal circulation (ECC). Under standardized conditions during the ECC basic parameters concerning the cardial hemodynamic (heart rate (HR); systolic (RRsys, mmHg), diastolic pressure (RR dia, mmHg) central venous pressure (CVP, mmHg); left atrial pressure (LAP, mmHg); left ventricular enddiastolic pressure (LVEDP, mmHg)) and ECG monitoring blood samples were performed: 1) prior to operation (op); 2) prior to CPB; 3) 1 h CPB; 4) 5 min after CPB; 5) 1 h after CPB; 6) 6 h postoperative (postop); 7) 24 h postop; 8) 48 h postop; 9) 10 days postop. Also the left atrial diameter (LAD, mm) and the left ventricular enddiastolic diameter at Q (LVEDD, mm) pre- and postop were documented with m mode echocardiography (Echo) and ejection fraction (EF, %) was calculated. The bypass operations were performed with intermittent aortic cross-clamping with open venae cavae (CVP: 0-5 mmHg) and moderate hypothermia. For the determination of ANP levels and TnT levels in arterial and venous blood, a double-antibody (AB) radioimmunoassay and an ELISA test were used. Concerning the patients with CAD there was a maximal increase of ANP from preoperative 90 +/- 10 (M +/- SEM) pg/ml (p < 0.05) up to intraoperative 380 +/- 38 pg/ml. Ten days postop, the ANP level was with 262 +/- 33 pg/ml still increased threefold in comparison to the preoperative level. TnT showed an increase from preoperative 0.02 +/- 0.01 ng/ml up to intraoperative 3.44 +/- 0.47 ng/ml. Ten days postop the TnT concentration was at the preoperative level with 0.13 +/- 0.11 ng/ml. Five minutes after bypass up to 48 h postop, ANP and TnT levels were correlated (p < 0.05, r = 3.4). There was an increase of the LAD from preoperative 42.2 +/- 1.1 mm up to 46.8 +/- 1.2 mm (p < 0.05) 10 days postop as determined by m-mode echo. LVEDD and EF changed from preoperative 51.1 +/- 0.9 mm and 73 +/- 2% to 54.5 +/- 1.2 mm and 65 +/- 4% 10 days postop. The significant increase of TnT (172-fold) indicates the cellular, myocardial injury, caused by the operation without signs in ECG recordings and no signs of congestive heart failure. The significantly increased ANP level up to the 10th day postop indicate sa very sensitive prolonged, postischemic dysfunction, which is not compensated 10 days postop. PMID- 11201030 TI - [Atrial fibrillation: healing by focal high frequency catheter ablation?]. AB - Atrial fibrillation is the most common sustained arrhythmia causing substantial morbidity and probably increasing the risk of death. Most commonly, it is divided into a paroxysmal form, when--by definition--episodes end spontaneously, or a persistent one that lasts and requires a medical or electrical intervention for its termination. It might be called permanent, when no further attempts seem to be indicated for its elimination. Until recently, therapeutic strategies aimed at preventing cardiac embolism and at restoring and maintaining sinus rhythm by antiarrhythmic drugs. Long-term efficacy of the latter approach is poor, since less than 50% of patients can be maintained in stable sinus rhythm when periods of more than 1 year are considered. Can atrial fibrillation be cured? More than ten years ago Cox and coworkers demonstrated that the surgical compartimentation of both atria (MAZE procedure) is able to abolish atrial fibrillation in up to 90% of patients with chronic paroxysmal and also persistent atrial fibrillation. However, all studies trying to imitate the MAZE procedure by electrophysiological catheter-based techniques applying radiofrequency energy to produce transmural linear lesions were either not successful or showed a non-acceptable complication rate, especially a high rate of cerebrovascular accidents. The rationale behind the principle of compartimentation of the atria is the reduction of the critical atrial muscle mass necessary to facilitate fibrillation of the atria. A different approach aiming especially at the problem of paroxysmal atial fibrillation is based on the observation that there might be a "focal trigger" responsible for the initiation of the atrial tachyarrhythmia and that by eliminating this focal trigger atrial fibrillation can be avoided. This hypothesis was first verified in patients by Haissaguerre et al., in fact experimental creation of "focal atrial fibrillation" was presented by Moe and Abildskov more than 30 years ago. During the last 3 years the concept of curing paroxysmal atrial fibrillation by applying focal radiofrequency lesions was supported by the results of several groups in more than 200 patients: 60 to 85% of patients can be cured, but in almost half of the cases more than one procedure is necessary. Most interestingly--and this is a finding of all investigators--more than 90% of the triggering ectopic foci are located in the pulmonary veins or in the pulmonary vein/left atrial junction. This concept is also supported by surgical experience from performing pulmonary vein isolations during open heart surgery. Most recently, the concept of eliminating the trigger was extended and applied to patients with established persistent atrial fibrillation. Until now, it has not been well established how many patients with paroxysmal atrial fibrillation are "good candidates" for a focal RF ablation procedure, nor is the risk of the procedure well defined. Besides the necessity of performing a transseptal catheterization there is the risk of cardiac embolism and pulmonary vein stenosis. The endpoint of the procedure is also not well defined: instead of trying to eliminate the "trigger" located in a pulmonary vein, it might be safer to isolate the "arrhythmogenic vein". This however, is a difficult task with current catheter technologies. It can be expected that new catheter designs for mapping and ablation and--maybe- the use of alternative energy sources--e.g., ultrasound, microwave--will make the procedure easier and applicable to more patients with drug refractory atrial fibrillation. PMID- 11201031 TI - Malignant vascular lesions of bone: radiologic and pathologic features. AB - The malignant vascular tumors of bone represent an uncommon diverse group of tumors with widely variable clinical and radiographic presentations. Although the radiographic imaging features of the lytic osseous lesions typically seen with this group of tumors are relatively nonspecific, the propensity to develop multifocal disease in an anatomic region is a feature that can be helpful in suggesting the diagnosis of a vascular tumor. The differential diagnosis varies according to the age of the patient and presence of solitary or multifocal disease. The histologic features are variable and range from tumors with vasoformative features to those that mimic mesenchymal neoplasm or metastatic carcinoma. Familiarity with the radiographic and pathologic spectrum of disease is essential for making an accurate diagnosis in this diverse group of neoplasms. This paper will provide a review of the nomenclature for the malignant vascular tumors of bone and discuss the radiographic and pathologic differential diagnosis. PMID- 11201032 TI - Helical CT in the primary trauma evaluation of the cervical spine: an evidence based approach. AB - This review provides a summary of the cost-effectiveness, clinical utility, performance, and interpretation of screening helical cervical spine CT for trauma patients. Recent evidence supports the use of helical CT as a cost-effective method for screening the cervical spine in high-risk trauma patients. Screening cervical spine CT can be performed at the time of head CT to lower the cost of the evaluation, and when all short- and long-term costs are considered, CT may actually save money when compared with traditional radiographic screening. In addition to having higher sensitivity and specificity for cervical spine injury, CT screening also allows more rapid radiological clearance of the cervical spine than radiography. Patients who are involved in high-energy trauma, who sustain head injury, or who have neurological deficits are candidates for CT screening. Screening with CT may enhance detection of other potentially important injuries of the cervical region. PMID- 11201033 TI - MR imaging of the Achilles tendon: overlap of findings in symptomatic and asymptomatic individuals. AB - OBJECTIVE: To differentiate MR imaging characteristics of symptomatic as compared with asymptomatic Achilles tendons. DESIGN: 1.5 T MR images of 94 feet (88 patients) with "abnormal" MR examinations were retrospectively evaluated and clinically correlated. Two masked, independent observers systematically evaluated for intratendon T2 signal, tendon thickness, presence of peritendonitis, retrocalcaneal bursal fluid volume, pre-Achilles edema, bone marrow edema at the Achilles insertion, and tears (interstitial, partial, complete). These findings were correlated with symptoms (onset and duration) and physical examination results (tenderness, palpable defects, increased angle of resting dorsiflexion). RESULTS: Of the 94 ankles, 64 ankles (32 females, 29 males) were clinically symptomatic. No relationship between Achilles tendon disorders and age or gender was identified. Asymptomatic Achilles tendons frequently demonstrated mild increased intratendon signal (21/30), 0.747 cm average tendon thickness, peritendonitis (11/30), pre-Achilles edema (12/30), and 0.104 ml average retrocalcaneal bursal fluid volume. Symptomatic patients had thicker tendons (0.877 cm), greater retrocalcaneal fluid volume (0.278 ml), more frequent tears (23/64), a similar frequency of peritendonitis (22/64) but less frequent pre Achilles edema (18/64). Sixty-four percent of the Achilles tendon tears were interstitial. Except for two interstitial tears in control patients, the majority of Achilles tears were in symptomatic patients (14/16). Only symptomatic tendons demonstrated partial or complete tendon tears. In addition, calcaneal edema was found almost exclusively in actively symptomatic patients. Thicker tendons were associated more often with chronic symptoms and with tears. When present in symptomatic patients, peritendonitis was usually associated with acute symptoms. The presence of pre-Achilles edema, however, did not distinguish acute from chronic disorders. CONCLUSION: There is significant overlap of MR findings in symptomatic and asymptomatic Achilles tendons. Furthermore, there is apparently a spectrum of disease in symptomatic tendons ranging from subtle intratendinous and peritendinous signal to partial and complete tendon tear. PMID- 11201034 TI - Malignant round cell tumours of bone: atypical clinical and imaging features. AB - OBJECTIVE: To describe the clinical, radiological and MRI features of six atypical cases of histologically proven appendicular Ewing sarcoma/primitive neuroectodermal tumour (PNET). DESIGN: Retrospective review of case notes and available imaging was carried out. PATIENTS: Six patients (4 male, 2 female; mean age 27 years, range 19-44 years), presenting over a 77-month period, were identified from the Bone Tumour Register. All had unusual clinical and imaging features for Ewing sarcoma/PNET. RESULTS AND CONCLUSIONS: Four tumours were centred on the distal femoral metaphysis, one in the proximal tibial metaphysis and one in the distal tibial metaphysis. Plain radiographs were available in four cases and showed minor cortical changes. MRI demonstrated a relatively small, eccentrically located intraosseous component with a large, eccentric extraosseous component. Extension into the epiphysis was seen in three cases and into the adjacent joint in two cases. Intraosseous "skip" metastases were present in three cases. The clinical and imaging features were atypical for conventional intraosseous Ewing sarcoma/PNET and the exact site of origin (intraosseous, periosteal or soft-tissue) was unclear. PMID- 11201035 TI - A comparative study of the accuracy of Ranawat's and Pierchon's methods to determine the centre of rotation in bilateral coxopathy. AB - OBJECTIVE: The objective of the study was to compare two methods (Ranawat's and Pierchon's) used to determine the centre of rotation of the hip and establish which method calculates a position nearer to the real centre of rotation. PATIENTS AND DESIGN: We selected 24 patients with unilateral osteoarthritis of the hip. The centre of rotation of the healthy hip was determined in two consecutive radiographic studies by superimposing a template of circles and using two axes as the reference lines (X-axis=teardrop line; Y-axis=a line perpendicular to the X-axis, drawn from the intersection of the ilio-ischiatic line and the teardrop line). After ensuring the stability of these references, both methods were applied to the same radiograph to determine which one established a centre of rotation nearer to the anatomical centre identified by the template of circles. RESULTS: When the values for the healthy hip are compared with those obtained using Ranawat's method, highly significant differences are observed for both X (P<0.0001) and Y (P<0.0001). When the results for the healthy hip are compared with the values obtained using Pierchon's method, neither the X (P=0.722 ) nor the Y values (P=0.112) show any significant differences. It would be advisable to use Pierchon's method to determine the centre of rotation during the preoperative planning for a total hip arthroplasty when the anatomical alteration is bilateral. PMID- 11201036 TI - Osteoblastoma-like osteosarcoma. AB - We report an osteoblastoma-like osteosarcoma in the right proximal fibula in a 22 year-old woman. Radiographs showed an irregular osteolytic lesion from the metaphysis to the epiphysis in the proximal fibula with partial destruction of cortical bone. Tissue from a biopsy indicated a typical osteoblastoma. Curettage and bone graft was performed. One year after the surgery, local recurrence occurred, and a wide excision was performed. Histological examination of the en bloc surgical specimen revealed the tumor had permeated through the host bony trabeculae, although the nuclear atypia was not marked. Immunohistochemical expression of MIB-1 was detected in 9.0% of cells. PMID- 11201037 TI - Tunneling Schmorl's nodes in an elderly woman treated for acute lymphoblastic leukemia. AB - We present a 70-year-old woman with pre-B acute lymphoblastic leukemia in whom serial imaging studies showed the development of multiple vertebral collapse, and communicating superior and inferior Schmorl's nodes creating a longitudinal channel ("tunneling" Schmorl's nodes) through the anterior aspect of T12 to L3 vertebral bodies of her osteoporotic thoracolumbar spine. This was observed after achieving complete remission of the disease and during maintenance therapy. The finding is felt to be secondary to iatrogenic exacerbation of osteoporosis. PMID- 11201038 TI - Mid-foot reconstruction following involvement of five bones by giant cell tumor. AB - We report on a patient who had giant cell tumor involving multiple bones of the mid-foot. The tumor originated from the navicular bone, but also destroyed the cuboid, and all cuneiform bones. This unusual presentation of giant cell tumor presented a therapeutic challenge for the surgeons. The patient was treated with en bloc resection and the bony defect replaced with a massive iliac crest graft which united within 9 months and has remained stable for 7 years without local recurrence, and with excellent function of the foot. PMID- 11201039 TI - Mandibulo-acral dysplasia. AB - We report on a 7 year-old-girl with mandibulo-acral dysplasia. When she was 3 years of age it mimicked scleroderma because of skin atrophy and later on a Hutchinson-Gilford progeria syndrome (HGP). Acro-mandibular dysplasia was diagnosed because of facial hypoplasia and mandibular hypoplasia. The bilateral proximal mid-humeral notch seen in this case is unusual. PMID- 11201040 TI - The historical development of salivary research in The Netherlands. PMID- 11201041 TI - Delayed embryonic development of mouse masseter muscle correlates with delayed MyoD family expression. AB - While the masseter muscle is known to have several unique developmental characteristics as compared with other skeletal muscles, little is known about its myogenesis. Thus, we examined the expression of myogenic marker and of myoD family gene mRNA from embryonic day (E) 11 to birth. The obtained results were compared with our earlier results of the mouse tongue muscle, which is also involved in oral functions. The mRNA quantities were determined by means of the reverse-transcription and competitive-polymerase chain-reaction techniques. The expression of myogenic marker mRNA indicated that differentiation and maturation in the masseter began at E13 as in the tongue, and were not yet completed at birth, although they were completed in the tongue. The expression of myoD, myogenin, and myf5 mRNA peaked later in the masseter (E17) than in the tongue (E13). The expression of MRF4 mRNA began later in the masseter (E15) than in the tongue (E13). These results suggest that the delayed expression of the myoD family genes in the masseter correlates with delayed differentiation and maturation, probably due to the later functional requirements of the masseter than of the tongue. PMID- 11201042 TI - Osteoprotegerin and osteoclast differentiation factor in tooth eruption. AB - A critical cellular event in tooth eruption is the formation of osteoclasts that are needed for bone resorption to form an eruption pathway. To analyze molecular regulation of osteoclast formation and activation, we examined the expression of osteoprotegerin (OPG), an inhibitor of osteoclast formation. In vivo, the gene expression of OPG is reduced in the dental follicle of the first mandibular molar of the rat at day 3 post-natally and in the mouse at day 5. This correlates with the days of maximal mononuclear cell influx and osteoclast numbers in the rat and mouse. Thus, inhibition of OPG gene expression on these days might allow osteoclasts to be formed and/or activated. In vitro studies demonstrated that both colony-stimulating factor-1 and parathyroid hormone-related protein reduced OPG gene expression in follicle cells, suggesting that these are candidate molecules for the in vivo inhibition of OPG expression. Osteoclast differentiation factor (ODF) immunolocalizes to the alveolar bone stromal cells adjacent to the follicle, whereby it might act to stimulate fusion of the mononuclear cells in the follicle. PMID- 11201043 TI - Evidence for charge domains on developing enamel crystal surfaces. AB - The control of hydroxyapatite crystal initiation and growth during enamel development is thought to be mediated via the proteins of the extracellular matrix. However, the precise nature of these matrix-mineral interactions remains obscure. The aim of the present study was to use a combination of atomic and chemical force microscopy to characterize developing enamel crystal surfaces and to determine their relationship with endogenous enamel matrix protein (amelogenin). The results show regular and discrete domains of various charges or charge densities on the surfaces of hydroxyapatite crystals derived from the maturation stage of enamel development. Binding of amelogenin to individual crystals at physiological pH was seen to be coincident with positively charged surface domains. These domains may therefore provide an instructional template for matrix-mineral interactions. Alternatively, the alternating array of charge on the crystal surfaces may reflect the original relationship with, and influence of, matrix interaction with the crystal surfaces during crystal growth. PMID- 11201044 TI - Butyric-acid-induced apoptosis in murine thymocytes and splenic T- and B-cells occurs in the absence of p53. AB - Butyric acid, an extracellular metabolite from periodontopathic bacteria, induces apoptosis in murine thymocytes, splenic T-cells, and human Jurkat T-cells. The present study examines the contributions of apoptosis-related proteins (Bcl-2, Bcl-XL, Bax, and p21WAF1/CIP1) in the regulation of T-cell death induced by butyric acid, using p53 knock-out (p53-/-) and wild-type (p53+/+) mice. The results of a DNA fragmentation assay indicated that thymocytes, splenic T-cells, and B-cells from p53-/- mice were susceptible to butyric-acid-induced apoptosis to a degree similar to those from p53+/+ mice. Moreover, butyric acid significantly induced apoptosis in lymphocytes from both p53+/+ and p53-/- mice in a concentration- and time-dependent fashion. Experiments with fractionated subpopulations of splenic T-cells revealed that DNA fragmentation was equally observed in CD4+ and CD8+ splenic T-cells from both p53+/+ and p53-/- lymphocytes. Activation of caspase-3, caspase-6, and caspase-8, but not of caspase-1, in butyric-acid-induced T-cell apoptosis occurred regardless of the presence of p53. Western blotting analysis of splenic T-cells showed that butyric acid treatment decreased Bcl-2 and Bcl-XL expressions in p53+/+ and p53-/- cells. Splenic T-cells had barely detectable Bax and p21WAF1/CIP1, regardless of whether butyric acid and/or p53 was present. These results suggest that butyric-acid mediated apoptosis of murine T-cells takes place via a pathway that is independent of p53, and is followed by the p53-regulated proteins Bax and p21WAF1/CIP1, which lower the levels of the apoptosis antagonists Bcl-2 and Bcl XL in cells. PMID- 11201045 TI - Cyclooxygenase-2-dependent prostaglandin E2 down-regulates intercellular adhesion molecule-1 expression via EP2/EP4 receptors in interleukin-1beta-stimulated human gingival fibroblasts. AB - Prostaglandin E2 (PGE2), which exerts its actions via EP receptors (EP1, EP2, EP3, and EP4), is a bioactive metabolite of arachidonic acid produced by cyclooxygenase (COX)-1 and/or COX-2. We have previously demonstrated that PGE2 down-regulates intercellular adhesion molecule-1 (ICAM-1) expression in interleukin-1beta (IL-1beta)-stimulated human gingival fibroblasts (HGF). In the present study, we investigated which COX was involved in down-regulation of ICAM 1 expression by PGE2 in IL-1beta-stimulated HGF and which subtypes of EP receptors modulated the ICAM-1 expression. NS-398, a specific COX-2 inhibitor, completely inhibited PGE2 production by IL-1beta-stimulated HGF, as did indomethacin, a COX-1/COX-2 inhibitor. Northern blot analysis and immunocytochemical staining showed that mRNA and protein of COX-2 were expressed in IL-1beta-challenged HGF, but not in unstimulated HGF, and that the expression of mRNA and protein of COX-1 was similar both in unstimulated and in stimulated cells. NS-398 and indomethacin enhanced ICAM-1 expression in IL-1beta-challenged HGF. EP1, EP2, and EP4 receptor mRNA was expressed in HGF according to reverse transcription/polymerase chain-reaction. PGE2, 11-deoxy-PGE1 (a selective EP2/EP4 agonist), and Butaprost (a selective EP2 agonist) attenuated IL-1beta-elicited ICAM-1 expression, although Butaprost was less potent than PGE2 and 11-deoxy PGE1. AH-23848B, an EP4 antagonist, antagonized the inhibitory effect of IL-1beta elicited ICAM-1 expression by PGE2. Sulprostone, an EP1/EP3 agonist, had no effect on IL-1beta-elicited ICAM-1 expression. Analysis of these data suggests that COX-2-derived PGE2 down-regulates ICAM-1 expression via EP2/EP4 receptors in IL-1beta-stimulated HGF. PMID- 11201046 TI - Collagen XII mutation disrupts matrix structure of periodontal ligament and skin. AB - Collagen XII has been postulated to organize the extracellular matrix (ECM) architecture of dense connective tissues such as the periodontal ligament (PDL) and skin. The objective of this study was to test this hypothesis in transgenic mice carrying a dominant interference mutation of collagen XII. The truncated alpha1(XII) collagen minigene construct MXIINC3(-), driven by the mouse alpha2(I) collagen promoter, was prepared and used to generate transgenic mouse lines. The PDL matrix fibers of molar teeth lost the ordered architecture characteristic of ligament tissue without noticeable inflammation. Cellular cement appeared to be disrupted at the PDL insertion. By confocal laser scanning microscopy, the PDL of transgenic mice demonstrated swollen and irregularly arranged collagen fibers associated with internal porosity. The skin of transgenic mice revealed the lack of matrix fiber structure in the papillary dermis. These results indicated that the dominant interference mutation of collagen XII disorganized the ECM architecture of PDL and skin. PMID- 11201047 TI - The in vivo expression of the collagenolytic matrix metalloproteinases (MMP-2, 8, -13, and -14) and matrilysin (MMP-7) in adult and localized juvenile periodontitis. AB - Periodontal inflammation is characterized by irreversible degradation of periodontal ligament collagen fibers leading to loss of tooth attachment. Cultured gingival keratinocytes and fibroblasts express, in vitro, various matrix metalloproteinases (MMPs) which can degrade fibrillar collagens. We hypothesized that several MMPs are also synthesized in vivo by sulcular epithelium, and analyzed the collagenolytic MMPs (MMP-2, -8, -13, and -14) and matrilysin (MMP-7) in gingival tissue specimens and gingival crevicular fluid from adult and localized juvenile periodontitis patients by in situ hybridization, immunohistochemistry, and Western immunoblotting. MMP-2, -7, -8, and -13 were expressed in gingival sulcular epithelium. MMP-7 and -13 were also located in fibroblasts and macrophages, and MMP-8 in neutrophils. MMP-8- and -13-positive cells/mm2 were higher in periodontitis gingiva when compared with healthy control tissue (p < 0.01). In periodontal diseases, gingival sulcular epithelium expresses several, rather than a single, collagenolytic MMPs, and this proteolytic cascade is evidently responsible for the tissue destruction characteristic of adult and juvenile periodontitis. PMID- 11201048 TI - Detection of a novel mutation in X-linked amelogenesis imperfecta. AB - Amelogenesis imperfecta (AI) is a heterogeneous group of inherited disorders of defective enamel formation. The major protein involved in enamel formation, amelogenin, is encoded by a gene located at Xp22.1-Xp22.3. This study investigated the molecular defect producing a combined phenotype of hypoplasia and hypomineralization in a family with the clinical features and inheritance pattern of X-linked amelogenesis imperfecta (XAI). Genomic DNA was prepared from buccal cells sampled from family members. The DNA was subjected to the polymerase chain-reaction (PCR) in the presence of a series of oligonucleotide primers designed to amplify all 7 exons of the amelogenin gene. Cloning and sequencing of the purified amplification products identified a cytosine deletion in exon VI at codon 119. The deletion resulted in a frameshift mutation, introducing a premature stop signal at codon 126, producing a truncated protein lacking the terminal 18 amino acids. Identifying mutations assists our understanding of the important functional domains within the gene, and finding another novel mutation emphasizes the need for family-specific diagnosis of amelogenesis imperfecta. PMID- 11201049 TI - An empirical test of the validity of the Oral Health Status Index (OHSI) on a minority population. AB - Disease varies in different populations based on sociodemographic variables, and there is limited understanding of this interaction. The purpose of this methodological study was to determine the validity of the Oral Health Status Index, a disease-based index, on a Hispanic population by comparing it with the NIDCR epidemiological measures of disease, with the addition of demographic and behavioral variables. The epidemiologic data were collected according to the criteria defined by the NIDCR, including: a modified Decayed Missing Filled Surfaces Index, gingival inflammation, calculus, and destructive periodontal disease measures. The demographic and behavioral variables were gathered from 240 interviews with Hispanic adults in two community clinics. Bivariate analysis was used to determine relationships between the descriptive epidemiologic, demographic, and behavioral variables and the Oral Health Status Index (OHSI). There were statistically significant differences (p < 0.05) in mean OHSI scores among the demographic variables age, education, income, and place of birth; and the behavioral variables alcohol consumption, flossing, and acculturation. Multiple regression analysis with the OHSI as the dependent variable showed that the statistically significant (p < 0.001) epidemiologic predictors were: percentage of Decayed Teeth/Decayed, Filled Teeth; Number of Replaced Teeth/Missing Teeth; and millimeters of mesial attachment loss. These collectively explained 47.49% of the variance in the regression. The addition of demographic variables to the epidemiologic regression identified age (p < 0.05), gender (p < 0.01), and place of birth (p < 0.01) as significant predictors that explained an additional 4.12% of the variance, collectively bringing the total explained variance to 51.61%. The behavioral variables did not contribute significantly to predicting the OHSI regression score. The Oral Health Status Index in this study is validated by its correlation with both the epidemiologic measures and the demographic variables. This combination of variables separated the Hispanics into Mexicans and Central/South Americans. PMID- 11201050 TI - Dentists' judgment strategies on prophylactic removal of mandibular third molars. AB - The number of molars selected for prophylactic removal varies widely among general dental practitioners and oral surgeons. To understand the basis for such variations, we investigated two hypotheses: (1) Individual judgment strategies will differ concerning the use of cues (items of information), and (2) few dentists will integrate the cues according to evidence in the literature. To analyze 30 general dental practitioners' (GDPs) and 10 oral surgeons' use of cues in the judgment preceding the treatment decision, we used the Brunwik's lens as a conceptual model. The cues were the patient's age, and the angular position and the degree of impaction of the molar. The clinical situation was simulated by written case descriptions. The proportion of variation explained by the cues and their combinations (total model) varied between 61% and 100% and between 4% and 76% as main effects. Two GDPs and one oral surgeon integrated the cues additively, i.e., any of the cues is independent of the other cues in the judgment. In general, the dentists integrated the cues interactively, i.e., the impact of one cue depends on the levels of some other cues. Even though most variations in judgments were accounted for by the cues, the dentists did not integrate the cues according to evidence in the literature and lacked insight into their decision-making thought processes. PMID- 11201051 TI - RGD peptide-induced apoptosis in human leukemia HL-60 cells requires caspase-3 activation. AB - RGD motif-containing peptides have been used in various studies of cell adhesion and growth. We report that RGD triggered apoptosis at a concentration of 1 mmol/L, whereas RAD-containing peptides failed to induce apoptosis in HL-60 cells. RGD-treated cells revealed internucleosomal DNA fragmentation. Western blot reveals caspase-3 activation in RGD peptide-treated cells. A caspase-3 inhibitor z-VAD-FMK completely blocked the apoptosis, but a caspase-1 inhibitor (Ac-YVAD-CMK) and caspase-2 inhibitor (z-VDVAD-FMK) did not block the apoptosis, suggesting that caspase-3 might have a critical role in the execution process of apoptosis induced by RGD. RGD peptides have been used extensively to inhibit tumor metastasis. Our results should help in further understanding the RGD peptide-induced apoptosis, which is important since RGD peptides have a potential role in therapies of the future. PMID- 11201052 TI - In vitro genotoxicity of terbutryn evaluated by the alkaline single-cell microgel electrophoresis "comet" assay. AB - Terbutryn, a s-triazine herbicide, is extensively used in agriculture as a selective pre- and postemergence control agent for most grasses and many annual broadleaf weeds in cereal and legume fields, and under fruit trees. Terbutryn was reported to degrade slowly, with half-lives of 240 and 180 days in pond and river sediment, respectively. The tendency of this herbicide to move from treated soils to water compartments through water runoff and leaching was demonstrated and residual amounts of terbutryn and its metabolites have been found in drinking water, and industrial food products, long after application. Although this herbicide may be regarded as a contaminant of our environment, only limited and inconsistent data exist concerning its genotoxic properties. In this study, the DNA-damaging ability of the herbicide was evaluated in the alkaline single-cell microgel-electrophoresis ("comet") assay by testing terbutryn in the presence of S9mix (rat liver homogenate containing microsomal enzymes plus cofactors) prepared with liver homogenate from both uninduced (basal) and aroclor 1254 induced rats. DNA damage was recorded in freshly isolated human peripheral blood leukocytes. A statistically significant increase in the extent of primary DNA damage, more pronounced in the absence of S9mix, took place only when terbutryn concentrations were high (100 and 150 microg/ml), in the presence of a concomitant mild cytotoxic effect. PMID- 11201053 TI - Successful separation of apoptosis and necrosis pathways in HaCaT keratinocyte cells induced by UVB irradiation. AB - UVB irradiation can induce apoptotic, necrotic, and differentiation pathways in normal human keratinocytes. The present study was undertaken to determine at what dose of UVB each of these pathways is induced and whether these pathways are distinct or overlapping. We have observed that UVB induces fragmentation of DNA in human HaCaT keratinocytes, in a bimodal manner. Low doses of UVB, 5-20 mJ/cm2, increase the levels of apoptosis as shown by increased levels of fragmented DNA, Fas, PARP, and FasL protein, and the number of apoptotic cells as assessed by FACS analysis. At higher doses of UVB (20 and 30 mJ/cm2) the number of apoptotic cells becomes reduced, as does the amount of Fas, PARP, and FasL protein. At these higher doses, cell viability is decreased as measured by DNA synthesis (BrdU labeling) neutral red uptake, which represents an increasing necrotic phenotype. Expression of markers of keratinocyte differentiation, involucrin, keratin K1, and keratin K10, are also observed to decrease with increasing UVB dose. These changes are accompanied by a further increase in DNA fragmentation. We conclude that low doses of UVB (5-20 mJ/cm2) induced an apoptotic pathway, whereas increasing doses (greater than 20 mJ/cm2) of UVB produce a direct necrotic effect and inhibit terminal differentiation. PMID- 11201054 TI - UVA-induced oxidative damage in retinal pigment epithelial cells after H2O2 or sparfloxacin exposure. AB - Retinal impairment is one of the leading causes of visual loss in an aging human population. To explore a possible cause for retinal damage in the human population, we have monitored DNA oxidation in human retinal pigment epithelial (RPE) cells after exposure to hydrogen peroxide (H2O2) or the quinolone antibacterial sparfloxacin. When H2O2- or sparfloxacin-exposed cells were further exposed to ultraviolet A (UVA) irradiation, oxidative damage to the DNA of these cells was greatly increased over baseline values. This RPE+pharmaceutical-UVA cell system was developed to mimic in vivo retinal degeneration, seen in mouse studies using quinolone and UVA exposure. DNA damage produced by sparfloxacin and UVA in RPE cells could be remedied by the use of antioxidants, indicating a possible in vivo method for prevention or minimization of retinal damage in humans PMID- 11201055 TI - Inhibition of platelet function by GSTM1-null human peripheral lymphocytes exposed to benzo(a)pyrene-induced challenge. AB - Recent epidemiological studies proposed that the glutathione S-transferase (GST) M1-null genotype may contribute to diseases associated with oxidative stress. The genetic polymorphism exhibited by the GSTM1 may be an important factor in risk toward oxidant chemicals. In this study, we investigated the effect of GSTM1-null genotype in lymphocyte and oxidative stress-dependent inhibition of platelet aggregation. To determine whether GSTM1 deficiency is a genetic determinant of cell toxicity toward oxidant chemicals, lymphocytes were incubated in vitro with low levels of benzo(a)pyrene (BaP), cumene hydroperoxide (CumOOH), or trans stilbene oxide that do not decrease cell viability, and were assessed for oxidative damage and for the lymphocyte-dependent inhibition of platelet response. Malondialdehyde and carbonyl levels, and the oxidation of cisparinaric acid, were used as biomarkers of oxidative stress in lymphocytes. Following stimulation by BaP or CumOOH, when peroxidation-dependent changes in these parameters were compared between the GSTM1-null genotype and the positive genotype, no significant differences were found between the two genotypes. On the other hand, preincubation of the lymphocytes with BaP or CumOOH attenuated their inhibitory action on ADP-induced platelet aggregation. However, our results indicate that lymphocytes of individuals with the GSTM1-null genotype have greater inhibitory activity on platelet function after exposure to BaP, but not CumOOH, although they are not more susceptible to in vitro oxidative stress. PMID- 11201057 TI - Lipopolysaccharide induces distinct alterations in the microtubule cytoskeleton of monocytes. AB - Microtubules are obligate functional elements of almost all eukaryotic cells. They are involved in a broad range of essential cellular functions and structural changes of this system may trigger cell death. Recently, we have reported that lipopolysaccharides inhibit in vitro microtubule formation due to exclusion of microtubule-associated proteins. The distinct epitopes of lipopolysaccharides responsible for these effects and the in vivo relevance of these data are unknown. Therefore, this study was conducted to elucidate the effects of lipid A, the biologically active motif of lipopolysaccharides, on microtubule formation in vitro and to prove whether lipopolysaccharides affect the microtubule architecture of cultured human monocytes in vivo. Despite a dose- and pH dependent inhibition of microtubule formation by lipopolysaccharides, inhibition of microtubule assembly could be mimicked by lipid A. Near-infrared two-photon microscopy revealed that human peripheral blood monocytes accumulate lipopolysaccharides. A vesicular distribution pattern of lipopolysaccharides within the monocytes was observed. Confocal laser scanning microscopy demonstrated alterations in the microtubule architecture of monocytes after incubation with lipopolysaccharides. Lipid A seems to be responsible for the observed crosstalk between lipopolysaccharides and microtubule proteins. Furthermore, our data indicate that lipopoly-saccharides may affect the microtubule architecture in human monocytes after intracellular accumulation directly. Therefore, we conclude, that the microtubule cytoskeleton is an essential intracellular target for sepsis-relevant bacterial components such as lipopolysaccharides. PMID- 11201056 TI - Regulation of phenobarbital-induction of CYP2B and CYP3A genes in rat cultured hepatocytes: involvement of several serine/threonine protein kinases and phosphatases. AB - We investigated the involvement of diverse protein kinases and phosphatases in the transduction pathways elicited by phenobarbital (PB), a well-known inducer of some hepatic cytochromes P450 (CYP). Different inhibitors or activators of protein kinases or phosphatases were assessed for their ability to modulate PB induction of CYP2B and CYP3A mRNA expression. Rat hepatocytes in primary culture were treated with the test compounds one hour prior to, and then continuously, in the absence or presence of 1 mmol/L PB for 24 h. By northern blot analysis of CYP2B1/2 and 3A1/2 gene expression, we first confirmed the negative role of the adenosine 3':5' cyclic monophosphate (cAMP)/protein kinase A pathway and the positive role of some serine/threonine protein phosphatases in the mechanism of PB-induction. The present data further suggested that Ca2+/calmodulin-dependent protein kinases II (independently of Ca2+) and extracellular signal-regulated kinases 1/2 (ERK1/2) might function respectively as positive and negative regulator in the PB-induction of CYP2B and CYP3A. In contrast, protein kinases C and phosphatidylinositol-3-kinase did not appear to be involved, while the role of tyrosine kinases remained unclear. We conclude that a complex network of phosphorylation/dephosphorylation events might be crucial for PB-induction of rat CYP2B and CYP3A. PMID- 11201058 TI - Intentionality, systems thinking, and collaboration: lessons for leadership from Congress 2000. PMID- 11201059 TI - Continuing education meets the learning organization: the challenge of a systems approach to patient safety. AB - Since the release of the report of the Institute of Medicine on medical errors and patient safety in November 1999, health policy makers and health care leaders in several nations have sought solutions that will improve the safety of health care. This attention to patient safety has high-lighted the importance of a learning approach and a systems approach to quality measurement and improvement. Balanced with the need for public disclosure of performance, confidential reporting with feedback is one of the prime ways that nations such as the United States, Canada, the United Kingdom, and Australia have approached this challenge. In the United States, the Quality Interagency Coordination Task Force has convened federal agencies that are involved in health care quality improvement for a coordinated initiative. Based on an investment in a strong research foundation in health care quality measurement and improvement, there are eight key lessons for continuing education if it is to parlay the interest in patient safety into enhanced continuing education and quality improvement in learning health care systems. The themes for these lessons are (1) informatics for information, (2) guidelines as learning tools, (3) learning from opinion leaders, (4) learning from the patient, (5) decision support systems, (6) the team learning together, (7) learning organizations, and (8) just-in-time and point-of care delivery. PMID- 11201060 TI - Shifting the culture of continuing medical education: what needs to happen and why is it so difficult? AB - A revolution in health care is occurring as a result of changes in the practice of medicine and in society. These include changing demographics and the pattern of disease; new technologies; changes in health care delivery; increasing consumerism, patient empowerment, and autonomy; an emphasis on effectiveness and efficiency; and changing professional roles. The issues raised by these changes present challenges for the content and delivery of the whole continuum of medical education. The ways in which continuing medical education (CME) needs to respond to these challenges are outlined. The Informed Shared Decision Making (ISDM) Project at the University of British Columbia is used as a case study to illustrate some of the practical problems in providing CME that address these current trends in health care, is effective, and is attractive to physicians. Two particular problems are posed: how to respond to a demonstrated need when there is no perceived need on the part of physicians and how to enable change agents on the margins to develop allies and get ownership from stakeholders and opinion leaders on the inside. Two strategies for change are discussed: the substantive incorporation of CME into the continuum of medical education and the involvement of patients in the planning and delivery of CME. A final challenge is raised for the leaders of CME to define and agree what "shifting the culture of CME" means and to make a commitment of time and energy into making it happen. PMID- 11201061 TI - Education in the workplace for the physician: clinical management states as an organizing framework. AB - Medical educators are interested in approaches to making selected relevant knowledge available in the context of problem-based care. This is of value both during the process of care and as a means of organizing information for offline self-study. Four trends in health information technology are relevant to achieving the goal and can be expected to play a growing role in the future. First, health care enterprises are developing approaches for access to information resources related to the care of a patient, including clinical data and images but also communication tools, referral and other logistic tools, decision support, and educational materials. Second, information for patients and methods for patient-doctor interaction and decision making are becoming available. Third, computer-based methods for representation of practice guidelines are being developed to support applications that can incorporate their logic. Finally, considering patients as being in particular "clinical management states" (or CMSs) for specific problems, approaches are being developed to use guidelines as a kind of "predictive" framework to enable development of interfaces for problem-based clinical encounters. The guidelines for a CMS can be used to identify the kinds of resources specifically needed for clinical encounters of that type. As the above trends converge to produce problem-specific environments, professional specialty organizations and continuing medical education course designers will need to focus energies on organizing and updating medical knowledge to make it available in CMS-specific contexts. PMID- 11201062 TI - Preventing "information overdose": developing information-literate practitioners. AB - The practice of medicine has been transformed by the convergence of a number of trends and developments. These include changes in the regulatory environment, scientific advances, the emergence of pressures for evidence-based medicine, advances in pharmaceutical knowledge and manufacture, and a shift in the nature of the patient/provider relationship. Many of these circumstances have been brought about or amplified by a variety of technological innovations. Collectively, these changes necessitate continuing--perhaps even continuous- learning and adaptation on the part of both new and established practitioners. At the heart of this need is the explosion of information and of information technologies, which shows little sign of abating. However, it is not simply the volume of information nor even its form that poses a challenge. It is also that outdated, incorrect, or unproven information is as accessible as correct, defensible, and reliable information. Therefore, doctors must be equipped not only with the ability to locate information but to evaluate its relevance and credibility. In short, they must be "information literate." Since both information and the technologies that give access to it are constantly expanding, a practitioner can never claim to be "information literate" in any absolute or final sense. It is a constantly evolving attribute and, alongside biomedical, clinical, pharmaceutical, legislative, and other domains, needs to form part of the provision of continuing education. Five propositions are advanced concerning this particular aspect of continuing medical education, and the article concludes by arguing that, in the same way that educating patients is the best defense against accidental overdose in the pharmaceutical sense, the best way to prevent "information overdose" is the education of practitioners. PMID- 11201063 TI - Using theory and research to shape the practice of continuing professional development. AB - As research has expanded in scope and diversity, application of new ideas to the programs that facilitate learning and change should have grown accordingly. However, the gap between the theories of how and why physicians learn and change their practices and the practical application of these theories appears to be wider. The research component of research and development in continuing professional development appears to be strong, but the development function appears to be weak. This presentation will describe some of the factors that have led to this gap between theory and practice and suggest some actions that may be taken to reduce this gap. Among the factors leading to the gap are the different perspectives of practitioners and scholars as to the purposes of research, the appropriate foci of studies, and the attributes of quality of studies related to continuing professional development. A traditional model of research is discussed and analyzed for its strengths and weaknesses as they relate to writing research that is relevant to practitioners. The role and function of the research problem and the conclusions of studies are described in terms of how these two parts of a research report can assist in the translation of theory and evidence into the practice. In order to illustrate how theory may be translated into practical tools and procedures, the application of the theory of change and learning to the assessment of readiness to change is reviewed briefly. Implications of this experience are described and steps that may be helpful in bridging the gap between theory and practice will be proposed. Finally, a system of research and development that can ensure a tighter link between research and practice is proposed. The next steps to achieve this kind of system are suggested in the conclusions. PMID- 11201064 TI - Congress 2000: a continuing medical education summit with implications for the future. AB - The expectations of attendees, the evaluations of themes, and the implications for continuing medical education (CME) identified by "Congress 2000: A Continuing Medical Education Summit on the Practices, Opportunities and Priorities for the New Millennium" are reviewed. A vision was identified with significant opportunities for CME to become a more valuable partner in and contributor to quality health care. The vision suggests that CME should be linked more closely to physician learning at the point of care and that technology might be used more successfully to address physician-learner needs by helping them to manage volumes of evidence for treating patients more effectively. At the same time, health care outcome data to analyze the need for and measure the effectiveness of educational interventions should become integrated into standards of practice for CME providers. Continuous improvement based on research about effective learning processes and outcomes should become an essential construct of the CME culture. Implications are summarized for the profession, organizational CME providers, individual CME professionals, and CME research from this new vision of CME crafted at Congress 2000. PMID- 11201065 TI - Neuromagnetic localization of N15, the initial cortical response to lip stimulus. AB - The initial cortical response of the trigeminal somatosensory evoked magnetic fields was measured for electrical stimulation of the lower lip in eleven subjects. The stimulus frequency was 0.7 Hz and stimulus intensity was nine times sensory threshold. The initial contralateral response was detected in 20 hemispheres at a latency of 14.6+/-1.3 ms and was named N15m. The equivalent current dipole of N15m was localized at the posterior bank of the central sulcus with anterior-superior orientation, and inferior to the dipole of N20m for median nerve stimulation. PMID- 11201066 TI - Postnatal expression of VEGF and its receptor flk-1 in peripheral ganglia. AB - The postnatal (P0-P12) and adult expression of vascular endothelial growth factor and its receptor flk-1 was investigated in superior cervical (SCG) and dorsal root ganglia (DRG) in mice by immunocytochemistry. At P0 all neurons in SCG and DRG contained VEGF. The number of VEGF-immunoreactive neurons in DRG but not in SCG, decreased postnatally and reached adult levels (34%) at P12. At P0 flk-1 was found in virtually all neurons in the SCG and in roughly half of the neurons in DRG. The number of flk-1 positive neurons then decreased and reached adult levels at P12. The findings demonstrate temporal changes in VEGF and flk-1 expression, suggesting developmental regulation of VEGF activity in peripheral ganglia. PMID- 11201067 TI - Interleukin-2 and interleukin-4 increase the survival of retinal ganglion cells in culture. AB - Natural cell death is a degenerative phenomenon observed during the normal development of the nervous system. The neuroprotective effects of cytokines produced by neuronal, glial or infiltrating cells on neurons have been extensively studied. In this work we studied the role of interleukin (IL)-2 and IL-4 on the survival of retinal ganglion cells (RGC) after 48 h in culture. Our results demonstrate that the effect of both ILs was dose-dependent and the treatment with either IL-2 (50 U/ml) or IL-4 (5 U/ml) induced a 2-fold increase in RGC survival. The effect of IL-4, but not of IL-2, was totally abolished by either 20 microM 5-fluoro-2'-deoxyuridine, an inhibitor of cell proliferation, or by 1 microM telenzepine, an inhibitor of M1 muscarinic receptor. Our results suggest that both cytokines could play an important role during the development of retinal tissue as well as during retina trauma. PMID- 11201068 TI - Clozapine, but not haloperidol, reverses social behavior deficit in mice during withdrawal from chronic phencyclidine treatment. AB - Phencyclidine (PCP) reduced social behavior (SB) in a dose- and time-dependent fashion. However, no such SB deficit was observed on repeated treatment with methamphetamine for 14 days. The SB deficit produced by treatment with PCP (10 mg/kg/day) for 14 days, which persisted for 28 days after withdrawal, was attenuated by clozapine (10 mg/kg/day) given for 7 days, whereas haloperidol for 7 days had no effect. Clozapine, but not haloperidol, alone at the same treatment dose increased SB in saline-treated mice. These results suggest that the proposed PCP model in mice will provide a tool to test beneficial effects of atypical antipsychotics on social dysfunction in schizophrenia, and contribute to our understanding of the mechanisms by which clozapine improves SB deficit. PMID- 11201069 TI - Effects of learning on cytochrome oxidase activity in cuttlefish brain. AB - Using cytochrome oxidase (CO) histochemistry, the effects of instrumental conditioning in cuttlefish central nervous system were examined. The posterior superior frontal lobe showed an increase of CO labelling just after training, whereas the anterior superior frontal lobe exhibited a decrease of CO staining 24 h post-training. These findings provide the first metabolic evidence for the involvement of the superior frontal lobe in learning and memory processes in cuttlefish. It is concluded that CO histochemistry can be used to provide a functional mapping of learning-induced plasticity in cuttlefish brain. PMID- 11201070 TI - Phencyclidine (PCP)-induced deficits of prepulse inhibition in monkeys. AB - Prepulse inhibition (PPI) of the acoustic startle reflex is a measure of sensorimotor gating which occurs in both rodents and humans. PPI is deficient in severe neuropsychiatric disorders such as schizophrenia. We investigated PPI in 10 adult monkeys (Cebus apella). Stimuli were 115 dB white noise startle pulses, either alone or preceded by 120 ms with a prepulse of either 8 or 16 dB above the 70 dB background noise. Experiments included a pretreatment baseline session and a session following treatment with either phencyclidine (PCP, 0.12 mg/kg, i.m.) or saline. Comparison of peak amplitudes indicated a significant intensity dependent decrease in startle response that was similar to that observed in humans under similar experimental conditions. PCP treatment significantly disrupted PPI, but did not reduce responses to startle pulses alone. These results provide the first demonstration of PPI in monkeys. The ability of PCP to induce schizophrenia-like deficits in PPI suggests that PPI in nonhuman primates may provide an important animal model for the development of novel anti schizophrenia medications. PMID- 11201071 TI - Nitric oxide modulates articular sensory discharge and responsiveness to bradykinin in normal and arthritic rats in vivo. AB - Nitric oxide is implicated in peripheral nociceptive processing. This study determined the effects of the nitric oxide synthase inhibitor, L-NAME, on neural discharge from articular C-fibre afferents innervating normal and arthritic ankle joints in anaesthetized rats. Intra-arterial injection of L-NAME (10-20 mg kg( 1)) increased neural discharge in normal and arthritic ankle joints, whereas D NAME (30 mg kg(-1)) had no effect. The excitation induced by L-NAME (20 mg kg( 1)) was reduced by co-injecting the nitric oxide precursor, L-arginine (50 mg kg( 1)). L-NAME (20 mg kg(-1)) also enhanced responsiveness to bradykinin (10 microg) but only in arthritic rats, whereas L-arginine (50 mg kg(-1)) reduced the excitation by bradykinin (30 microg) in both groups. These results provide evidence that nitric oxide modulates articular C-fibre activity and reduces responsiveness to bradykinin. PMID- 11201072 TI - Additive effect of mPer1 and mPer2 antisense oligonucleotides on light-induced phase shift. AB - It is well known that light induces both mPer1 and mPer2 mRNA in the suprachiasmatic nucleus. We have reported that mPer1 antisense oligonucleotides (ODNs) inhibited the light-induced phase delays of mouse locomotor rhythm. In this study, we asked whether both or either mPer1 or mPer2 expression is necessary to induce the phase shift. We examined the effects of inhibition of mRNA expression on light-induced phase delays of mouse circadian behavior rhythm. Light-induced phase delays were moderately attenuated by microinjection of mPer1 or mPer2 antisense ODN, but not by mPer3 antisense or mPer1, mPer2 scrambled ODNs, whereas following simultaneous injection of both mPer1 and mPer2 antisense ODNs they disappeared. The present results suggest that acute induction of mPer1 and mPer2 gene play an additive effect on photic entrainment. PMID- 11201073 TI - Roles for nitric oxide and arachidonic acid in the induction of heterosynaptic cerebellar LTD. AB - In cerebellar slices conjunctive pairing of parallel fibre (PF) stimulation with depolarization of Purkinje cells (PCs) induces a long-term depression (LTD) of PF synaptic transmission that spreads to unpaired PF inputs to the same cell. Inhibitors of NO synthase (7-nitro-indazole), soluble guanylate cyclase (ODQ) and PKG (KT5823) all prevented depression at each of two independent PF pathways to a single PC. Inhibition of NOS also unmasked a platelet activating factor (PAF) mediated synaptic potentiation of possible presynaptic origin. LTD was also prevented by the phospholipase A2 inhibitor OBAA but was rescued by co-perfusion with arachidonic acid. We conclude that NO and diffusible products of phospholipase A2 metabolism are potential mediators of the spread of cerebellar plasticity at the single cell level. PMID- 11201074 TI - Peripheral neuroglial death induced by cisplatin administration in newborn rats. AB - To determine the target of cytotoxicity of cisplatin (CDDP), we injected newborn rats with 2 mg/kg CDDP and examined the trigeminal ganglion for possible cell death. A nick translation method for DNA fragmentation revealed CDDP-induced glial cell death. DNA fragmentation was detected in both Schwann cells and satellite cells. Satellite cell death was observed as early as 0.5 day after injection, most frequent at 1-3 days and subsided thereafter. The incidence of neuronal death was very low and comparable to that observed in vehicle control rats. CDDP has selective toxicity to peripheral glial cells, though the damage did not culminate in cell death in adults. The glial toxicity may contribute to clinical symptoms of CDDP neuropathy. PMID- 11201076 TI - Modulation of alpha2beta4 neuronal nicotinic acetylcholine receptors by zinc. AB - A study was made of the modulation of nicotinic acetylcholine receptors by the divalent cation zinc. Rat neuronal nicotinic receptors (alpha2beta4) were expressed in Xenopus oocytes and membrane currents evoked by acetylcholine (ACh currents) were recorded using a two microelectrode voltage clamp. In non-injected oocytes, or in oocytes expressing alpha2beta4 receptors, Zn2+ by itself (1 microM 4 mM) generated only very small membrane currents. In contrast, in oocytes expressing alpha2beta4 receptors, Zn2+ greatly and reversibly increased the ACh current, without affecting considerably its time course. The ACh current potentiation by Zn2+ was weakly dependent on the membrane potential (2.33+/-0.10 times the control current at -100 mV vs 2.04+/-0.06 at -60 mV, suggesting that Zn2+ interacts with the receptor in the vestibule of the ion channel or at an external domain of the protein. The inward rectification of control and Zn2+ potentiated ACh-currents was similar. We conclude that Zn2+ positively and reversibly modulates neuronal nicotinic receptors in a practically voltage independent manner and without affecting their rate of desensitization. These results will help to understand better the roles played by Zn2+ in brain functions. PMID- 11201075 TI - Induction of hippocampal glial cells expressing basic fibroblast growth factor RNA by corticosterone. AB - A transcriptional regulation of bFGF expression via both gluco- and mineralocorticoid receptors is known to exist. In the present study the glial nuclear fraction of bFGF transcripts was studied in sham-operated (SHAM), adrenalectomized (ADX), and corticosterone-treated ADX rats in subregions of the dorsal hippocampal formation. A substantial increase was observed in the population of bFGF RNA-expressing glial cells after acute corticosterone treatment (10 mg/kg, s.c.) in subregions of the CA1 area and the dentate gyrus but no changes were observed after adrenalectomy. The levels of glial nuclear bFGF transcripts were similar in all the experimental groups. These data suggest that in a subpopulation of hippocampal glial cells corticosterone regulates bFGF gene expression transcriptionally in an on/off manner. PMID- 11201077 TI - Galanin/alpha2-adrenoceptor interactions in telencephalic and diencephalic regions of the rat. AB - The aim of this study was to evaluate whether galanin could affect central alpha2 adrenoceptors in telencephalic and diencephalic regions in the rat using quantitative receptor autoradiography with the alpha2 agonist radioligand [3H]p aminoclonidine. Galanin 1 nM significantly and substantially increased the Kd value of the [3H]p-aminoclonidine binding sites in the medial hypothalamus and amygdala by 86% (p < 0.01) and 73% (p < 0.05) respectively. The Bmax value was only significantly increased with 3 nM galanin in the amygdala and the medial hypothalamus (both p < 0.05). The antagonist M35 counteracted the increase of the Kd values of the alpha2-adrenoceptor agonist binding sites produced by galanin 1 nM in the amygdala and the medial hypothalamus (both p < 0.001). These findings suggest the existence of an antagonistic galanin/alpha2 adrenoceptor interaction in the medial hypothalamus and amygdala that may be of relevance for alpha2 adrenoceptor-regulated neuroendocrine functions and food intake. PMID- 11201078 TI - Action monitoring, error detection, and the basal ganglia: an ERP study. AB - The error negativity (Ne or ERN) is an event-related brain potential component, which is assumed to reflect error detection. Recently it has been hypothesized that the basal ganglia are assumed to play a crucial role in error detection. In the present study we ask whether the Ne is altered in patients with Parkinson's disease (PD), who have an impaired function of the basal ganglia. We recorded the Ne in patients and in matched controls, while they performed different tasks that require a relatively high cognitive control, which is supposed to pose particular problems on PD. The Ne was in fact smaller in the patients than in the controls in all tasks. Our results suggest an impairment of error detection in PD for different types of demanding tasks. This supports the hypothesis that the basal ganglia do play an important role for error detection in action monitoring. PMID- 11201079 TI - Calcium inhibits willardiine-induced responses in kainate receptor GluR6(Q)/KA-2. AB - A number of studies have demonstrated that willardiine [(S)-1-(2-amino-2 carboxyethyl) pyrimidine-2,4-dione] is a useful agonist for the activation of AMPA/kainate receptors. Here we examine the effect of extracellular calcium on currents evoked by willardiine in HEK 293 cells expressing the GluR6(Q)/KA-2 kainate receptor subunits. At a concentration of 1.8 mM, Ca2+ inhibited the currents induced by 100 microM willardiine by approximately 50%. When extracellular Na+ ions were replaced with Ca2+ ions there were no measurable inward currents. We conclude that Ca2+ inhibition of the willardiine-induced response is concentration dependent. PMID- 11201080 TI - Timbre-specific enhancement of auditory cortical representations in musicians. AB - Neural imaging studies have shown that the brains of skilled musicians respond differently to musical stimuli than do the brains of non-musicians, particularly for musicians who commenced practice at an early age. Whether brain attributes related to musical skill are attributable to musical practice or are hereditary traits that influence the decision to train musically is a subject of controversy, owing to its pedagogic implications. Here we report that auditory cortical representations measured neuromagnetically for tones of different timbre (violin and trumpet) are enhanced compared to sine tones in violinists and trumpeters, preferentially for timbres of the instrument of training. Timbre specificity is predicted by a principle of use-dependent plasticity and imposes new requirements on nativistic accounts of brain attributes associated with musical skill. PMID- 11201081 TI - Electron microscopic evidence for different myelination of rat septohippocampal fibres. AB - Rat septohippocampal fibres are known to originate from GABAergic parvalbumin containing, fast-firing, fast-conducting neurons and from cholinergic slow firing, slow-conducting neurons. In the present electron microscopic study, based on immunocytochemical demonstration of parvalbumin and choline acetyltransferase in transverse and horizontal septal sections, it was shown that parvalbumin immunoreactive fibres are myelinated, but the vast majority of cholinergic fibres are not. As revealed, especially in horizontal sections, the cholinergic axons show considerably finer calibres than parvalbumin-containing ones. These results confirm and extend our previous light microscopic findings. It can be concluded that differences in conduction velocities, presence or absence of myelin sheaths and differences axonal diameters are correlated in the septohippocampal pathway. PMID- 11201082 TI - Decrease in spinal CGRP and substance P is not related to neuropathic pain in a rat model. AB - We tested the hypothesis that the decrease in spinal levels of SP and CGRP after peripheral nerve injury is related to neuropathic pain. We compared two groups of rats, both of which were subjected to unilateral transection of the inferior and superior caudal trunks between the S1 and S2 spinal nerves. One group exhibited well-developed neuropathic signs after the nerve injury, whereas the other group showed poorly developed signs despite the same nerve injury. The decrease in immunoreactivity of CGRP and SP in the S1 dorsal horn (injured segment) was not significantly different between the two groups. These results suggest that the decrease in spinal levels of CGRP and SP after peripheral nerve injury is not related to neuropathic pain. PMID- 11201083 TI - Early loss of dendritic spines in murine scrapie revealed by confocal analysis. AB - Confocal analysis of dye-filled neurons has revealed a significant early loss of dendritic spines in a murine scrapie model in which neuron loss occurs in the hippocampus. An 18% loss of spines was found at 109 days, > 50 days before neuron loss occurs, and by 126 days a 51% spine loss was found. Spine loss is concurrent with synapse loss, axon terminal degeneration and a decrease in long term potentiation in this model. Preceding these changes is the deposition of disease specific PrP at 70 days, which may initiate the damage to dendritic spines and the subsequent degeneration of synapses. We suggest that these changes underlie the development of clinical disease in the transmissible spongiform encephalopathies. PMID- 11201084 TI - Effect of brain-derived neurotrophic factor on the release of substance P from rat spinal cord. AB - Brain-derived neurotrophic factor (BDNF) can produce hyperalgesia in the adult rat. Here we assessed whether changes in the spinal release of the nociceptive peptide substance P (SP) contributes to this effect. Antibody-coated microprobes revealed a significant basal release of SP in the dorsal horn in vivo that was increased following acute knee inflammation. Microinjection of BDNF into the grey matter (0.5 microl, 10(-5) M) altered SP release neither in rats with normal knees nor in rats with inflamed knee joints. In the lumbar dorsal horn slice preparation in vitro, superfusion with BDNF (100 ng/ml) could reduce SP release evoked by electrical dorsal root stimulation without modyfing SP basal outflow. It is unlikely, therefore, that enhanced spinal SP release mediates the hyperalgesic effect of BDNF. PMID- 11201085 TI - Intercellular action of nitric oxide increases cGMP in cerebellar Purkinje cells. AB - cGMP is thought to play a role in cerebellar signalling yet its production within Purkinje cells has never been detected. In the present study, the hydrolysis of a fluorescent substrate analogue, 2'-O-anthranyloyl cyclic GMP, by type 5 phosphodiesterase was monitored within Purkinje cells in slices and in culture. Nitric oxide, either endogenously released from adjacent neurons or pharmacologically applied, accelerated the rate of hydrolysis in a manner that was dependent on soluble guanylyl cyclase, demonstrating that nitric oxide triggers cyclic GMP production in Purkinje cells, which in turn activates type 5 phosphodiesterase. We conclude that NO acts as an intercellular messenger in the cerebellar cortex and that parallel fibre terminals are a probable source of nitric oxide. PMID- 11201086 TI - Transient expression of SorCS in developing telencephalic and mesencephalic structures of the mouse. AB - Here we describe the expression of a third member of the VPS10 domain containing receptor family, SorCS, during mouse embryonal and early postnatal nervous system development. SorCS is expressed in a unique transient and dynamic pattern in regions where cells proliferate, as well as in areas where already differentiated cells reside, including the cerebral cortex, the ventral tegmental area, and the globus pallidus. Transcripts were absent from fiber tracts hinting at a neuronal expression. The only exception was hybridization signals on the developing optic nerve correlating with the appearance of astrocytes migrating into the retina. PMID- 11201087 TI - Auditory event-related potentials differentiate patients with normal pressure hydrocephalus and patients with concomitant Alzheimer's disease verified by brain biopsy. AB - We studied 51 patients with clinical symptoms and CT findings suggesting normal pressure hydrocephalus (NPH). Tests included head MRI, auditory event-related potentials (ERPs), thorough neuropsychological testing and intraventricular intracranial 24 h pressure recording and infusion testing. A brain biopsy was also obtained to verify a concomitant dementing process (Alzheimer's disease; AD). Patients were divided into subgroups according to the need of shunt and the biopsy findings, and their ERPs were analysed blindly. The present results suggest that non-invasive ERPs aid in the differentiation of pure NPH from NPH with concomitant AD. PMID- 11201088 TI - Origins of spontaneous and noxious stimuli-evoked miniature EPSCs in substantia gelatinosa. AB - The origins of spontaneous and noxious stimuli-evoked glutamatergic miniature excitatory postsynaptic currents (mEPSCs) in substantia gelatinosa (SG) neurons were investigated by using whole-cell voltage-clamp technique on adult rat spinal cord slice. The properties of mEPSCs of SG neurons from rats either neonatally capsaicin-treated or sciatic nerve ligated showed no difference from those of intact SG neurons, indicating independence of spontaneous mEPSCs on primary afferent fibers. In the presence of tetrodotoxin (TTX), capsaicin, which noxiously stimulated fine primary afferent fibers, caused increase of the mEPSCs frequency, but did not affect the amplitude profiles or mean amplitudes. TTX affected neither the spontaneous mEPSCs nor capsaicin-induced mEPSCs frequency increase. The results suggest that spontaneous mEPSCs in SG are mediated by presynaptic spontaneous glutamate release predominantly originating from interneuron terminals rather than from primary afferent terminals; under noxious stimulation, however, mEPSCs frequency increase is mediated by primary afferent excitation. PMID- 11201089 TI - Synchronization of visual responses in the superior colliculus of awake cats. AB - Multi-unit responses to moving stimuli were recorded simultaneously from several sites in the superior colliculus of awake cats. Correlation analysis revealed that response synchronization was a prominent feature of visually evoked neural activity in both superficial and deep collicular layers. Responses at about half of the recordings separated by < or = 1 mm showed significant correlations. The synchronized responses oscillated in the gamma frequency range (30-70 Hz) which contrasts to conditions in anaesthetized cats where oscillations predominantly occurred in the alpha and beta frequency range (10-20 Hz). Response synchronization was most pronounced with coherent motion stimuli and broke down with incoherent stimuli. These results agree with previous findings on corticotectal synchronization and support the hypothesis that synchronization in the millisecond range serves to group collicular neurons into functionally coherent assemblies. PMID- 11201090 TI - Changes in spinal cholecystokinin release after peripheral axotomy. AB - The gene expression of cholecystokinin (CCK), a neuropeptide with anti-opioid properties, has been reported to be upregulated in some primary sensory neurons after a peripheral nerve lesion. We have recently demonstrated that the upregulation of CCK mRNA is not accompanied by an increased potassium-evoked release CCK-like immunoreactivity (CCK-LI) 2-4 weeks after a complete transection of the sciatic nerve. The potassium-evoked release of CCK-LI at earlier and later time points has, however, not been studied. The aim of the present in vivo microdialysis study was to monitor how the basal and stimulated extracellular level of CCK in the dorsal horn of the spinal cord is affected at various time points after a complete transection of the sciatic nerve (axotomy). During the first week after transection of the sciatic nerve a tendency towards an elevation of the potassium-induced (100 mM in the perfusion fluid) release of spinal CCK-LI was observed. In contrast, no potassium-induced release of CCK-LI could be detected 2-3 weeks and 2 months after axotomy. No significant effect was observed on the basal extracellular levels of CCK-LI in the dorsal horn. The present study provides further support for the notion that the adaptive changes in the dorsal horn 2 weeks and later after a deafferentiation injury do not include an increased release of CCK. PMID- 11201091 TI - Presenilin-2 (PS2) expression up-regulation in a model of retinopathy of prematurity and pathoangiogenesis. AB - Presenilin-2 (PS2; AD4), a regulator of intercellular signaling during CNS development and cell fate determination, appears to be involved in pathogenic processing of beta-amyloid precursor protein (betaAPP) into potentially neurotoxic beta-amyloid (Abeta) peptides. The PS2 gene promoter contains multiple DNA binding sites for the relatively rare hypoxia-inducible transcription factor HIF-1, suggesting that PS2 expression may be a sensitive indicator of decreased oxygen availability. We have used a cycled hypoxia/hyperoxia (10-50% O2) protocol followed by normoxia (20% O2) as a retinal model of retinopathy of prematurity to induce neovascularization (NV) in rat pups. Retinal cell nuclear extracts from pups undergoing hypoxia exhibited a dramatic increase in HIF-1-DNA binding, followed by a delayed (2-7 day) elevation of PS2 RNA message and protein. PS2 gene activation during hypoxia may direct cellular fate towards pathoangiogenesis and intercellular PS2-mediated signaling dysfunction. PMID- 11201092 TI - Kainate-induced K+ efflux and plasma membrane depolarization in cultured cerebellar granule cells. AB - It is becoming increasingly evident that activation of ionotropic glutamate receptors leads to significant changes in cytosolic [K+] ([K+]c), a major determinant of the plasma membrane (PM) potential, Em. Since Em affects fluxes of key cations, such as Ca2+, it is important to precisely quantify [K+]c and Em in neurons exposed to glutamate receptor agonists. Here we studied the relationships between [K+]c and Em in primary cultures of cerebellar granule cells, and found that kainate elicits a rapid drop in [K+]c below 10 mM. Using patch electrodes containing 10 or 150 mM K+, we determined that kainate depolarizes the PM to -2 or -28 mV, respectively. Therefore, the actual PM depolarization elicited by kainate is much larger than that routinely measured with K+-rich electrodes. PMID- 11201093 TI - Sexual pheromone or conventional odors increase extracellular lactate without changing glucose utilization in specific brain areas of the rat. AB - Brain extracellular lactate levels increase following physiological stimuli. Monitoring lactate levels might be a tool for detecting dynamic changes in brain activity. In this study we compared changes of extracellular lactate in selected brain areas with rates of glucose utilization as measured by the [14C]2 deoxyglucose method, following olfactory stimulation. Conventional (green pepper essence, heptanal, exanal, octanal) and, above all, non-conventional (sexual pheromone) odors increased lactate in the rhinencephalum, but not in the striatum. Glucose utilization did not change in any area. This discrepancy may result from the different temporal resolution of the two methods employed and/or from the clearance of lactate, whose tissue content increases transiently following neuronal activation as a reflection of the initial oxygen debt. PMID- 11201094 TI - Temporal and spatial dependency of the ventriloquism effect. AB - The perception of the spatial location of an auditory stimulus can be captured by a spatially disparate visual stimulus, a phenomenon known as the ventriloquism effect. This study investigated the temporal and spatial dependency of this illusion. In the temporal domain, only disparities of 50-100 ms were perceived as simultaneous, and disparities where the visual stimulus occurred before the auditory stimulus were more effective in creating the illusion. In the spatial domain, the illusion was elicited most strongly at spatial disparities below spatial discrimination thresholds. There was also a significant interaction between temporal and spatial disparities. These results indicate that both temporal and spatial parameters are critical in the perception of real world objects in extrapersonal space. PMID- 11201095 TI - Keratinocyte growth factor prevents ischemia-induced delayed neuronal death in the hippocampal CA1 field of the gerbil brain. AB - Fibroblast growth factors (FGFs) are polypeptides with various biological activities in vivo and in vitro, and their receptors are expressed in the widespread and specific neuronal populations of the brain. In this study, we asked whether keratinocyte growth factor (KGF), one of the FGF superfamily, would express in the brain, and have neuroprotective against ischemic brain injury. In situ hybridization analysis revealed that intense silver grains for KGF mRNA are observed in the neuronal cells of the cerebral cortex, hippocampus and amygdala in gerbil brain. Continuous cerebroventricular infusion of KGF (20 microg) for a 7 day period to gerbils starting 2 days before temporary right carotid artery occlusion (20 min) resulted in a higher survival rate than seen in vehicle treated ischemic animals. Subsequent histological examinations showed that KGF effectively prevented delayed neuronal death of the hippocampal CA1 region. In situ detection of DNA fragmentation (TUNEL staining) revealed that ischemic animals infused with KGF contained fewer TUNEL-positive neurons in the hippocampal CA1 field than those infused with vehicle alone at the forth and seventh day after ischemia. KGF-treated brain showed over-expression of KGF mRNA in the neuronal cells of the cerebral cortex, hippocampus only in the right hemisphere, which was the side of carotid artery occlusion, 8-10 h after ischemia. These findings suggest that KGF has a protective effect against ischemic hippocampal neuronal damage in vivo, which may provide a new therapeutic strategy in the survival and reconstruction of neurons in response to cerebral injury. PMID- 11201096 TI - Fetal cell grafts provide long-term protection against scrapie induced neuronal loss. AB - We have transplanted fetal neurons to prolong hippocampal pyramidal cell survival in a mouse scrapie model in which 50% of CA1 pyramidal cells have died by day 180 of the 250-day incubation period. Cells prepared from embryonic PrP deficient mice were intracerebrally injected into infected mice on day 150 and groups killed on day 171 and with terminal disease. Neuron counts and CA1 depth measurements were made on semi-serial sections using an image analysis system. Both grafted groups retained more CA1 neurons than controls injected with medium alone, and showed greater depth of CA1 than controls. This new approach may have potential as a late-stage therapy for TSEs for which there are currently no available treatments. PMID- 11201097 TI - An fMRI study with written Chinese. AB - Event-related functional magnetic resonance imaging (ER-fMRI) was used to investigate how the human brain processes phonology and transforms a word's visual form (orthography) into phonological form during reading in logographic Chinese, a writing system that differs markedly from alphabetic languages. We found that reading aloud of irregular words produced larger MR signal intensity changes over extensive regions involving left infero-middle frontal cortex, left motor cortex, right infero-frontal gyri, bilateral anterior superior temporal areas, and anterior cingulate cortex. Right superior parietal lobule, the cuneus in bilateral visual cortex, and thalamus participated in the processing of irregular, but not regular, words. These findings were discussed in comparison to neuroimaging findings from alphabetic languages, as well as in relation to models of reading. PMID- 11201098 TI - Role of corticostriatal and nigrostriatal inputs in malonate-induced striatal toxicity. AB - The striatal neuronal loss evident following cellular metabolic compromise may be dependent upon the presence of glutamate and dopamine within the striatum. In order to investigate the relative roles of corticostriatal and nigrostriatal projections in malonate-induced neuronal loss, the extent of toxicity was quantified in animals with cortical lesions to deplete the striatum of glutamate, nigrostriatal lesions to deplete the striatum of dopamine, or both. We found that malonate-induced striatal toxicity was significantly reduced following lesions of either the glutamatergic or dopaminergic afferents to the striatum. The extent of attenuation following the loss of both inputs within the same animal was similar to that seen following lesions of either alone. These data suggest that malonate induced toxicity in the striatum depends upon the integrity of interactive influences from both glutamatergic and dopaminergic afferents. PMID- 11201099 TI - Optical responses to micro-application of GABA agonists in the embryonic chick brain stem. AB - We investigated optical responses induced by micro-application of muscimol and baclofen in the embryonic chick brain stem. Muscimol evoked biphasic optical signals which were similar to those induced by GABA. The first component was a dye-dependent absorption change that reflected membrane depolarization, and the second component was an intrinsic optical change coupled with changes in the membrane potential. On the other hand, baclofen did not elicit any optical change. The optical responses induced by muscimol persisted in the presence of picrotoxin and 2-hydroxysaclofen, suggesting that they contain a component which is not mediated by classical GABA receptors. PMID- 11201100 TI - Equivalent disruption of regional white matter microstructure in ageing healthy men and women. AB - Diffusion tensor imaging was used to measure regional differences in brain white matter microstructure (intravoxel coherence) and macrostructure (intervoxel coherence) and age-related differences between men and women. Neuropsychiatrically healthy men and women, spanning the adult age range, showed the same pattern of variation in regional white matter coherence. The greatest coherence measured was in corpus callosum, where commissural fibers have one primary orientation, lower in the centrum semiovale, where fibers cross from multiple axes, and lowest in pericallosal areas, where fibers weave and interstitial fluid commonly pools. Age-related declines in intravoxel coherence was equally strong and strikingly similar in men and women, with evidence for greater age-dependent deterioration in frontal than parietal regions. Degree of regional white matter coherence correlated with gait, balance, and interhemispheric transfer test scores. PMID- 11201101 TI - [Molecular mechanisms for preprotein translocation across the cytoplasmic membrane of E. coli--structure changes of SecA and SecG coupled with translocation]. PMID- 11201103 TI - [Quantum chemical approach to radiation-induced DNA damage]. PMID- 11201102 TI - [Selectins and their carbohydrate ligands in cellular recognition]. PMID- 11201104 TI - [A vital role for glycosphingolipid synthesis during development and differentiation]. PMID- 11201105 TI - [Regulation of chromatin and transcription by methyl-CpG binding proteins]. PMID- 11201106 TI - [Laboratory evolution approach to protein engineering]. PMID- 11201107 TI - [Genesis and mechanism of ischemia-reperfusion injuries]. PMID- 11201108 TI - [Thyroidectomy for Graves' disease]. AB - In the late 19th century, surgeons in central Europe attempted to perform thyroidectomy for Graves' disease. Theodor Billroth, Theodor Kocher, and their colleagues made numerous contributions to progress in surgical methods. Preoperative arterial ligation, lobectomy, and second-stage operations were performed to reduce operative mortality rates. Lobectomy and partial resection of the contralateral lobe were performed in the 1900s, and subtotal thyroidectomy, which became the standard procedure of the day, was performed in the 1920s. Developments in medical therapy, such as iodine (1923) and thiouracil (1943) administration, also decreased postoperative mortality and morbidity rates. In 1954, radioiodine therapy was found to yield satisfactory results in achieving remission of Graves' disease. Currently, surgery for Graves' disease is indicated only in patients with large goiters or who require rapid remission. PMID- 11201109 TI - [The history and evolution of coronary artery bypass grafting]. AB - It is nearly 40 years since the introduction of coronary artery bypass grafting (CABG) in humans. A. Carrel (1910) attempted the first CABG in animals and G. Murray (1954) succeeded in performing experimental CABG using the internal mammary artery (IMA). The first reported CABG using the IMA in humans was performed by R. Goetz using the sutureless technique in 1960. V. Kolessov (1964) performed the first sutured bypass grafting using the IMA. From 1962 to 1967, human CABG using autogenous saphenous vein grafts was performed by D. Sabiston (1962). H. Garrett (1964), D. Kahn (1966), and R. Favaloro (1967). Saphenous vein grafting became the most common CABG technique for the next two decades. In Japan, Y. Sezai et al. performed CABG using the free femoral artery, we performed CABG using the IMA, and S. Asada et al. performed CABG using the saphenous vein in 1970. In 1986, F. Loop et al. reported that the long-term survival rate of CABG was significantly higher when the IMA rather than the saphenous vein was used. IMA grafting, supplemented by the gastroepiploic artery, inferior epigastric artery, and radial artery, has enabled complete arterial revascularization to be performed in almost all patients. In the graft selection for CABG, the first choice is the left IMA and the second choice is the right IMA. The third choice is the gastroepiploic artery and/or radial artery, depending on the target anastomotic site, degree of stenosis, size of the distal graft, and in situ or free use. PMID- 11201110 TI - [History of breast cancer surgery and its perspectives]. AB - At the end of the 19th century, surgical treatment of breast cancer was revolutionized by the introduction of the Halsted radical mastectomy. Haagensen, who studied under one of Halsted's students, further strengthened the foundations of the technique, and the Halsted operation became the standard radical breast cancer surgery worldwide. This may have been responsible for the persistence of this operation, particularly in Japan. Some Halstedian surgeons espoused the extended radical mastectomy or super-radical mastectomy. However, breast conserving surgery is now becoming the most common technique. In the early 1970s breakthroughs in the understanding of the biology of breast cancer led to a new era of adjuvant therapy. Consequently current surgical management of breast cancer is no longer possible without considering other therapeutic modalities. Consistent with this change, it should be realized that the disease is no longer diagnosed at the same stage as it was at the time of Halsted. Although the ultimate patient outcome is not likely to be influenced solely by locoregional treatment, surgery will continue to be employed as the most effective treatment modality, and every effort should be made to prevent locoregional tumor spread. PMID- 11201111 TI - [History and advances in the surgical treatment of lung cancer]. AB - In 1933, Graham successfully performed one-stage pneumonectomy for lung cancer. Four years later, Ozawa (Japan) also performed pneumoenctomy for lung cancer. Unfortunately, progress in the surgical treatment of lung cancer in our country was interrupted by World War II. After the war, the first report of resection in 3 cases of lung cancer was published by Ishikawa in 1949. In the 1950s, poorer surgical outcomes were reported from Japan in terms of resection rate or long term survival compared with those in Western countries. However, since the 1960s, there has been great progress in Japan in the treatment of lung cancer, due to the marked increase in the number of lung cancer patients, developments in endoscopy and imaging devices, and also in surgical procedures such as anatomical lung resection, lymph node dissection, combined resection of adjacent organs, and bronchoplastic surgery. Surgical mortality was over 20% in the early years. However, it has currently decreased to a few percent. The long-term survival rate for resected lung cancer patients has improved remarkably in recent years. Among stage IIIA cases, the optimal surgical outcome is achieved in the group undergoing chest wall resection for T3 N0 M0 disease. However, patients with IIIA N2 disease generally have a poor surgical outcome. Therefore, trials of induction therapy are being carried out at many institutions. PMID- 11201112 TI - [The history of surgical treatment for esophageal carcinoma in the 20th century in Japan]. AB - In the 20th century surgical results in the treatment of esophageal carcinomas significantly improved in Japan. For the reason, I review the trends in esophageal cancer surgery in Western countries and discuss the reasons for the choice of surgical procedures. In Japan, esophageal cancer surgery was initiated with the reports of surgical results presented by Professors Seo and Osawa at the Congress of the Japan Surgical Society held in 1933. Subsequently, the results in esophageal cancer patients undergoing surgical resection were improved with the progress in anesthesia. Subsequent to the establishment of the Japan Society of Esophageal Diseases in 1965, any institutes performed esophagectomy for esophageal carcinomas, and the procedure accounted for less than 2% of all operative deaths in Japan. The main reason for this reduction in the number of surgical deaths was improved perioperative care for major complications (cardiopulmonary failure and anastomotic leakage). In particular, the surgical procedure for curative lymphadenectomy called three-field dissection significantly improved surgical prognosis. In the last 10 years, the relationship between the number of positive lymph nodes and surgical prognosis was demonstrated in advanced esophageal cancers, while endoscopic mucosal resection was also performed for early esophageal cancers as a curative treatment. In the next century, better treatment should be designed for individual patients based on fundamental studies and clinical trials. PMID- 11201113 TI - [History of gastric cancer surgery]. AB - The successful surgical treatment of gastric cancer in 1881 was a breakthrough not only in gastric but also in digestive surgery. By the beginning of the 20th century, the modalities of gastric surgery had almost reached the present level. At that time, the successful resection rate was 20% and mortality rate 50% in patients undergoing gastrectomy for cancer. During the 30 years after World War II, the extent of gastric resection increased, lymphadenectomy was introduced, and the number of concomitant resections of organs in addition to the stomach also increased. Since the 1980s, modified surgery has been performed in patients with early-stage gastric cancer. Based on data collected by the Japanese Research Society for Gastric Cancer, the current resection rate is 91.3%, mortality rate 1.0%, and 5-year survival rate 71.6% in patients with gastric cancer. PMID- 11201114 TI - [Historical review of colorectal cancer surgery]. AB - The classical standard surgical technique for rectal carcinoma, abdominoperineal excision (Miles operation), has been gradually replaced by sphincter-saving surgery and more than 70% of rectal carcinomas are treated by anterior resection in which autosuture machines have played a major role in recent years. Wide lateral lymphadenectomy has been replaced by autonomic nerve preservation because of the high frequency of sexual and urinary dysfunction. Total mesorectal excision (TME) proposed by Heald et al which ignores the lateral nodes of the pelvic wall is the most popular technique in Western countries. The concept of TME is contradictory to that of wide lateral lymphadenectomy and the true merits of the latter should be examined in the near future. Minimally invasive surgery, including various procedures of local excision of low rectal tumors and colonoscopic polypectomy, has given great benefits to many patients. In Japan there seems to have been a lack of interest in adjuvant radiotherapy and chemoradiotherapy in the past, but they should be more seriously considered for the adjuvant treatment of advanced rectal carcinoma in the future. PMID- 11201115 TI - [Progress in surgery for hepatocellular carcinoma]. AB - Before 1980, the surgical procedure for liver resection was limited to major hepatectomy. Anatomical resection for subsegmentectomy based on liver anatomy was established after 1980. Surgical techniques to resect nonpalpable and nonvisible tumors and devices to reduce blood loss in the resection plane of the liver are mandatory when performing subsegmentectomy. Intraoperative ultrasound has played a major role in the progress achieved. Hepatectomy procedures preservation of the inferior right hepatic vein, and preoperative portal vein embolization have also contributed to progress in the field of liver surgery. PMID- 11201116 TI - [Carcinoma of the pancreatic head]. AB - Focusing mainly on invasive ductal carcinoma of the pancreas, the history of radical surgery for this type of cancer is reviewed, including pancreatoduodenectomy, total pancreatectomy, extended radical surgery with main vascular resection and extended lymphadenectomy/retroperitoneal soft-tissue clearance, pylorus-preserving pancreaticoduodenectomy. In addition, duodenum preserving pancreatic head resection, which has recently attracted attention in this field, as an operative technique for less-malignant, noninvasive intraductal papillary adenocarcinoma is also reviewed. PMID- 11201118 TI - [General surgery and medical history]. PMID- 11201117 TI - [History of surgery for cholelithiasis: from the era of cholecystostomy to laparoscopic surgery]. AB - Since Stalpert von der Wiel first incised the abdominal wall for bile drainage in a patient with an intraabdominal abscess due to gangrenous cholecystitis with calculi in 1684, the problems inherent in the treatment of cholelithisiasis have received attention from surgeons working in this field. However, the major event was the development of the technique of cholecystectomy by Langenbuch in 1882 opening a new era in surgery for cholelithiasis. Subsequently numerous advances were made in cholecystectomy, choledochotomy, choledochoenterostomy, and sphincteroplasty associated with progress in the diagnostic techniques and instrumentation necessary to perform surgery for cholelithiasis. However, the outcomes of these methods were criticized, and they were gradually abandoned due to development of minimally invasive endoscopic or laparoscopic surgery. The development of laparoscopic cholecystectomy revolutionized the history of biliary surgery. In the 21st century, the best treatment will be available to all patients with the use of ultramodern technologies such as telesurgery and robotic surgery. PMID- 11201119 TI - [UNOS-selection criteria and order of priority for the candidate of liver transplantation]. PMID- 11201120 TI - [Clinicopathologic study on chronic pancreatitis with diffuse irregular narrowing of the main pancreatic duct]. AB - We studied the clinicopathologic features of 13 cases of chronic pancreatitis with diffuse irregular narrowing of the main pancreatic duct (MPD). It occurs frequently in relatively elder men. Diffuse irregular narrowing of the MPD and stenosis of the common bile duct on ERCP, and swelling of the pancreas on US/CT were detected in all cases. An autoimmune mechanism might be involved in the etiology at least in 5 patients with hypergammaglobulinemia and positive autoantibodies. Surgical therapy was performed in 8 patients and 3 patients were treated with steroids. No patients showed recurrence of pancreatitis. Histologic findings were characterized by diffuse lymphoplasmacytic infiltration with marked interstitial fibrosis in the pancreas, obliterated phlebitis of the pancreatic veins. Similar inflammatory process involved the bile duct and the gallbladder. These histologic findings were similar to those of multifocal fibrosclerosis. Chronic pancreatitis with diffuse irregular narrowing of the MPD is overlapped with autoimmune pancreatitis in many cases, but may be a variant of multifocal fibrosclerosis involving the pancreas in some cases. PMID- 11201121 TI - [A case of small cell carcinoma of esophagus successfully treated by chemotherapy with CPT-11 and CDDP]. PMID- 11201122 TI - [A case of ileal atypical carcinoid with multiple liver metastasis]. PMID- 11201123 TI - [A case of multiple gastro-intestinal angiosarcoma]. PMID- 11201124 TI - [A case of gastro-renal-shunt induced non-cirrhotic recurrent hepatic encephalopathy effectually treated by balloon-occluded retrograde transvenous obliteration]. PMID- 11201125 TI - [A case of hypogenesis of the median segment of the liver complicated with Chilaiditi syndrome]. PMID- 11201126 TI - [A case of granulocyte-colony stimulating factor producing squamous cell carcinoma of the gall bladder]. PMID- 11201127 TI - [A case of chronic pancreatitis with primary biliary cirrhosis whose diameter of pancreatic duct was rapidly changed]. PMID- 11201128 TI - [Present status and prospective view in liver transplantation in Japan]. PMID- 11201129 TI - [Study of free to total prostate specific antigen ratio in the detection of patients with prostate cancer]. AB - BACKGROUND: We investigated the clinical usefulness of free to total serum prostate specific antigen (PSA) ratio (F/T ratio) in order to improve the specificity of total PSA measurement for detecting prostate cancer. METHOD: In this study 129 patients with total PSA level 4-20 ng/ml underwent transrectal ultrasound guided sextant biopsy. Serum samples were assessed for total PSA, free PSA and the F/T ratio calculated. All patients were pathologically diagnosed as benign prostatic hyperplasia or prostate cancer. RESULTS: Of 129 patients 21 had prostate carcinoma (PCa) and 108 had benign prostatic hyperplasia (BPH) from the results of prostate biopsies. The mean of total PSA were not significantly different between men with PCa and with BPH. The mean of free PSA for PCa was significantly lower than that for BPH (p = 0.043). Furthermore, the mean of F/T ratio was significantly different between PCa and BPH group (p = 0.0014). The F/T ratio had a higher specificity than total PSA at all levels of sensitivity in detecting prostate cancers. Sensitivity, specificity and accuracy for cancer detection at a cut off 0.12 was 90.4%, 51.8% and 58.1%, respectively. Also, free PSA was as useful as F/T ratio for cancer detection when analyzed in receiver operating characteristic curves analysis. When determined the cut off number of free PSA at 0.78 ng/ml, the sensitivity, specificity and accuracy for cancer detection were 61.9%, 66.7% and 65.9%, respectively. CONCLUSION: This study indicated that the F/T ratio and free PSA could improve the specificity without impairing the sensitivity for detecting PCa in patients with 4-20 ng/ml of total PSA. PMID- 11201130 TI - [An optimal follow-up protocol for renal cell carcinoma based on the occurrence of recurrences after surgery]. AB - INTRODUCTION AND OBJECTIVE: The tumor biology of renal cell carcinoma (RCC) remains poorly understood and the prognosis of which is unpredictable. To define an optimal follow-up protocol in nonmetastatic RCC, tumor recurrences and the clinical course were assessed in the patients who had undergone nephrectomy. PATIENTS AND METHODS: Between March 1972 to July 1999, 265 patients with PT1-3N0 (Nx) M 0 RCC underwent radical or partial nephrectomy. Clinicopathological variables were compares with the time of the first recurrence, site of metastasis and reason for diagnosis. RESULTS: In July 1999, the median (range) follow-up for the surviving patients was 50 (1-244) months. Metastases were diagnosed in 45 of the 265 patients (17%). Sixty percent of the patients had their metastases diagnosed within 3 years and 87% by 6 years. The incidence and the mean time to first diagnosis of recurrence were 9.0% and 43.6 months for pT1, 32.4% and 39.6 months for pT2, and 32.7% and 25.0 months for pT3. Metastatic sites and the mean time of diagnosis were 40.6 months in lung (46.7%), 26.1 months in bone (17.8%), 18.6 months in retroperitoneal organs (11.1%), 38.0 months in liver (6.7%), 51.0 months in thyroid gland (4.4%) and 31.0 months in brain (2.2%). Most recurrence in lung, retroperitoneal organs and liver were incidentally diagnosed, whereas recurrences in bone, thyroid gland and brain had some symptoms associated with metastases. Incidence of lung metastasis in pT1 (9 patients, 56%) and pT2 (6, 55%) was greater than that in PT3 (6, 33%). In contrast, incidence of abdominal metastasis (retroperitoneal organs and the liver) in pT3 (4 patients, 33%) was grater than pT1 (2, 12%) and PT2 (1, 16%). CONCLUSIONS: The results indicate that the risk of tumor progression and site of metastasis seemed to depend on original TNM stage. Therefore stage specific postoperative follow-up protocol should be considered. The yearly follow-up may suffice for pT1a patients after surgery. For pT1b and pT2 patients, the follow-up should be intense during the first 3 years by a routine chest X-ray. For pT3 patients, the follow-up during the first 2 years may be important. Particularly, considering the high incidence of abdominal metastasis in these patients, examination by CT scan is recommended every 6 months in the first 2 years. No need for bone scintigraphy and brain CT was indicated for asymptomatic patients. PMID- 11201131 TI - [Ischemic heart disease in patients with erectile dysfunction]. AB - BACKGROUND: Erection is an hemodynamic event and accordingly, erectile dysfunction is closely related with ischemic heart diseases. Sufficient study has yet to be made of this relation. METHOD: Fifty-eight patients with erectile dysfunction participated in the present study. Intracavernous injection tests and color Doppler examination were conducted for assessment of erectile function. For patients with history of ischemic heart disease, we referred to their doctor for data from their examinations. For patients otherwise, chest X-rays and electrocardiograms in the resting position were obtained and also electrocardiograms following exercise. Echocardiograms, treadmill test results, thallium exercise scintigrams, and coronary angiograms were obtained as requires for diagnosis. RESULTS: Eighteen patients (31.0%) were diagnosed as ischemic heart disease or at high risk. Although 6 of them had been already diagnosed with ischemic heart disease, 12 were newly diagnosed by the exercise tests. Among these 18 patients 16 had one or more significant risk factors for ischemic heart disease such as age, hyperlipidemia, and diabetes mellitus. 3.7% of patients whose peak systolic velocity in the cavernous artery was equal to or exceeded 35 cm/sec had ischemic heart disease or were at high risk. 54.8% of patients with peak systolic velocity of less than 35 cm/sec had ischemic heart disease or were at high risk. CONCLUSIONS: In erectile dysfunctional patients, incidence of complications with symptomatic or asymptomatic ischemic heart disease was found to be high. Therefore, in patients with risk factors or low peak systolic velocity in the cavernous artery, exercise tests should be implemented prior to treatment of erectile dysfunction. PMID- 11201132 TI - [Electromyographic study of the striated urethral sphincter by using the bulbocavernosus reflex: study on change of sacral reflex activity caused by bladder filling]. AB - PURPOSE: The change of sacral reflex activity of the striated urethral sphincter in the urine storage phase is investigated using evoked potential reaction of the bulbocavernosus reflex (BCR). METHODS: Eleven normal male subjects and 13 male patients with neurogenic bladder due to suprasacral (C3-C7) spinal cord injury (SCI patients) were investigated. Within the SCI patients, five were complete SCI and 8 were incomplete SCI. BCR was elicited by electrical stimulation of dorsal nerve of the penis, and the evoked potential of the BCR was recorded with a concentric needle electrode from the periurethral striated muscle. BCR was performed both at empty and at filled bladder respectively, and changes of the amplitudes (AMP) were examined. Moreover, the changes of AMP affected by bladder filling were compared between the normal subjects and the SCI patients. RESULTS: In both the normal subjects and the SCI patients, AMP increased at the filled bladder as compared with that of the empty bladder. In addition, the change of AMP was statistically bigger in the SCI patients (a ratio of amplitude at filled bladder/amplitude at empty bladder: 4.73 +/- 3.90) than in the normal subjects (the ratio: 1.32 +/- 0.44). CONCLUSION: Sacral reflex activity was accelerated by bladder filling in both the normal subjects and SCI patients. And the acceleration in the SCI patients was more remarkable than that in the normal subjects. In addition to the conventional evaluation of the integrity of sacral reflex arc by BCR examination, the observation of changes of BCR affected by bladder filling may provide the information for the continuity of sacral segment and supraspinal micturition center. PMID- 11201133 TI - [A case of ectopic prostatic tissue in urinary bladder and uretero-seminal vesicle fistula with ipsilateral aplastic kidney]. AB - A case of ectopic prostatic tissue in urinary bladder and uretero-seminal vesicle fistula with ipsilateral aplastic kidney is reported. A 29-year-old man was admitted to our hospital for residual sensation and perineal pain. Ultrasound examination revealed a cystic change in the right side of urinary bladder. C.T. and M.R.I. revealed a defect of a right kidney and ipsilateral ureteral dilation and seminal vesicle swelling. A cystscopy under lumbar anesthesia revealed a edematous cystic change of the right side of trigone and defect of the right ureteral orifice. Trans urethral resection of the wall of urinary bladder was simultaneously performed. And the contents of the cyst were sperum and old red blood cells. A retrograde ureterograph showed blind-ending ureter at L5 level and seminal vesicle swelling. A resected bladder tissue contained prostatic tissue. After operation he was free from complaints. Uretero-seminal vesicle fistula with ipsilater aplastic kidney is rare disease. In addition a case complicated ectopic prostatic tissue in urinary bladder was not reported in Japanese medical literature. PMID- 11201134 TI - [Renal cell carcinoma in acquired cystic disease of the kidney manifested by spontaneous renal hemorrhage]. AB - Acquired cystic disease of the kidney (ACDK) is a common phenomenon in long-term adult dialysis patients with end-stage renal disease. Renal hemorrhage and neoplastic transformation of the cyst are two major complications of this entity and these two can occur independently. Here we describe a 65-year-old man with a history of hemodialysis-dependent end-stage renal failure for 12 years presented with macroscopic hematuria and right flank pain. Investigations revealed right massive perirenal and subcapsular hematoma with ACDK. The hemorrhagic state required nephrectomy of the right kidney. Histological study showed ACDK with massive subcapsular and perinephric hematoma containing minimal clear cell carcinoma region(0.5 cm in diameter). Although a causal relationship between renal hemorrhage and renal cell carcinoma in this patient was unproven, the present case suggests radical surgery can be a recommendable treatment modality of hemorrhagic ACDK. PMID- 11201135 TI - [Liver transplantation and tuberculosis]. AB - Although liver transplantation in Japan has rapidly expanded its indication to adult patients, our experience and measures in posttransplant tuberculosis is still limited. Early posttransplant patients under immunosuppressants generally have a higher risk for tuberculosis and the risk in liver recipients follows that in lung recipients. Rejection treatment is one of the risk factors for infection, dissemination, and mortality of tuberculosis. Drug-induced liver injury by anti tuberculotic drugs and their interaction with immunosuppressants, combined infection, and increased susceptibility to rejection in posttransplant tuberculosis are major obstacles in the treatment. Evidence-based consensus in the diagnosis and treatment of posttransplant tuberculosis, as well as establishment of speedy and reliable screening method in potential organ donors, are in a pressing need. PMID- 11201136 TI - [Limits of nucleic acid amplification tests for diagnosis of smear negative pulmonary tuberculosis]. AB - STUDY OBJECTIVES: To assess the usefulness of commercial kits of nucleic acid amplification test (NAAT) for diagnosis of smear negative (SN) pulmonary tuberculosis. DESIGN AND PATIENTS: Retrospective study of patients who were diagnosed as, or suspected of pulmonary tuberculosis during 3 years from January 1996 to December 1998 in Fukujuji Hospital which has 100 beds for tuberculosis patients. MEASUREMENTS AND RESULTS: 145 smear-negative culture-positive pulmonary tuberculosis patients are entered to our analysis. The DNA-based amplification test kit (Amplicor Mycobacterium Tuberculosis Test (AMPL), Roche Diagnostic Systems, Basel, Switzerland) detected 39.2% (20/51, 95% confidence interval (CI): 25.8-52.6%) of smear-negative culture-positive (SNCP) pulmonary tuberculosis cases. The RNA-based amplification test kit (Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test (AMTDT), Gen-Probe Inc., San Diego, Calif., USA) detected 40.5% (15/37, 95% CI: 24.7-56.3%) of SNCP pulmonary tuberculosis cases. For both NAATs (AMPL and AMTDT), between two groups with and without the NAAT at diagnosis of SNCP pulmonary tuberculosis, there was statistical difference in culture-positive rate (proportion of positivity in sputum culture tests at diagnosis), but no statistical difference in maximum number of colony of Mycobacterium tuberculosis (MTB). When stratified for the culture-positive rate, adjusted sensitivity for SNCP patients was 44.2% (AMPL) and 40.4% (AMTDT) respectively. On the other hand, among 245 patients with sputum AMPL positive results during the 3 years, 8 were smear-negative culture-negative (SNCN), only one out of these 8 cases was judged as true active tuberculosis without treatment. Among 89 patients with sputum AMTDT positive results, 7 were SNCN, and 3 out of them were judged as true active tuberculosis without treatment. CONCLUSION: Usefulness of commercial NAAT kits (AMPL and AMTDT) to diagnosis SN pulmonary tuberculosis is limited in the point of sensitivity. PMID- 11201137 TI - [Desensitization therapy for allergic reactions of antituberculous drugs- evaluation of desensitization therapy according to the guideline of the Japanese Society for Tuberculosis]. AB - We prospectively evaluated the effectiveness of desensitization therapy for cases showing side-effects to antituberculous drugs (Isoniazid and Rifampicin) according to the guideline proposed by the Treatment Committee of the Japanese Society for Tuberculosis. Nineteen patients (23-88 years old, male 9, female 10) who had experienced adverse effects after receiving antituberculous drugs and underwent desensitization therapy between August 1998 and March 2000 were studied. Underlying diseases were 14 cases of pulmonary tuberculosis, 2 cases of cervical tuberculous lymphadenitis, 1 case of pulmonary atypical mycobacteriosis, 1 case of pulmonary tuberculosis and tuberculous pleuritis, 1 case of pulmonary tuberculosis and tuberculous lymphadenitis. The regimens of treatment for tuberculosis were INH + RFP + EB in 8 cases, INH + RFP + EB + PZA in 7 cases, INH + RFP + SM in 2 cases, INH + RFP + SM + PZA in 1 case, and INH + RFP in 1 case. Adverse reactions were 8 cases of eruption, 7 cases of drug fever, 3 cases of drug fever and eruption, and 1 case of drug fever and cervical lymphadenopathy. The causative drugs suggested from DLST or the clinical course were RFP in 17 cases and INH in 8 cases. The clinical effect of desensitization therapy for these antituberculous drugs was good in 14 out of the 17 cases (82%) for RFP, and in 6 out of 8 cases (75%) for INH. The effectiveness rate of the present desensitization therapy according to the guideline of the Japanese Society for Tuberculosis was almost equal to that of previous desensitization therapy, and the clinical results were almost same in present and previous studies despite the different methods of administration of the antituberculous drugs. PMID- 11201138 TI - [A case of pulmonary tuberculosis diagnosed by DNA amplification methods from transbronchial lung biopsy materials]. AB - The hybridization assay using polymerase chain reaction (PCR) is useful for rapid detection of Mycobacterium tuberculosis (M. tuberculosis). A 77-year-old female was admitted to our hospital complaining of cough, and examination of the sputum culture showed M. tuberculosis. Her chest X-ray showed a variety of abnormal shadows, such as a cavity lesion, multiple coin lesions, and infiltrates. Malignant disease was also suspected to be involved, with the complication of pulmonary tuberculosis. Specimens were obtained by transbronchial lung biopsy (TBLB) from coin lesions. The hybridization assay using PCR on the TBLB specimens showed M. tuberculosis gene expression. She was treated with anti-tuberculous drugs. All shadows in her chest X-ray were improved six months after admission. She was remained well without recurrence for more than two years after admission. The hybridization assay using PCR with TBLB specimens is useful for the detection of M. tuberculosis. PMID- 11201139 TI - [Pulmonary Mycobacterium gordonae infection treated with clarithromycin]. AB - We reported a case of 51-year-old female immunocompetent patient with pulmonary Mycobacterium gordonae infection. The patient complained persistent cough and sputum and occasionally hemosputum. Chest radiograph and computed tomography (CT) of the lung showed bronchiectasis and small nodules in middle lobe. Bronchofiberscopy was performed twice, and bronchial washing specimen repeatedly revealed acid-fast bacilli. The organism was identified as Mycobacterium gordonae by biochemical tests and direct sequence method. She was treated with clarithromycin (400 mg/day) over 6 months and the chest CT findings showed improvement. The case was considered to be sensitive to clarithromycin in vitro drug susceptibility test. The case suggested that clarithromycin was a useful therapeutic agent to Mycobacterium gordonae infection. PMID- 11201140 TI - [Thinking about tuberculosis in Osaka City]. AB - The incidence rate of tuberculosis in Osaka City (104.2 per 100,000 population) is extremely high, namely 3 times higher than the national average. Why the tuberculosis situation of Osaka City is so bad? The reason could be summarized as follows: Before the end of the World War II (1945), it was the sequelae of high prevalence observed in the era of Meiji, Taisho and early years of Showa. However, after the World War II, especially from the Heisei era (1989-), it is deeply affected by the influence of socio-economic background in Japan. Osaka City is characterized as the city of merchants and small enterprises. And therefore, the city substantially has the nature of the locality that brings in or produces some kinds of social vulnerability such as temporary laborers and homeless people. Of the tuberculosis patients in Osaka City, about 20% are homeless. In addition, patients of the smear positive infectious tuberculosis are often discovered among temporary laborers who change their residences and job sites from place to place and contact widely with citizens. These two are the most difficult problems in tuberculosis control program of Osaka City. In the meantime, there are many citizens who are careless of their health and do not follow the law or social rule, and this has apparently no direct connection with the problems of tuberculosis. However, it might be one of the factors of an undesirable trend of tuberculosis in Osaka City. In order to improve such a unfavorable tuberculosis situation in Osaka City, effective and strong supporting activities to the tuberculosis program are essentially needed. And these activities must be done from the standpoint of health-promotion, namely, health education for citizens and improvement of social environmental conditions to maintain healthy and cultural life. PMID- 11201141 TI - [Molecular genetic approaches to Mycobacterium tuberculosis]. AB - Recent progress of molecular genetics has been providing tools for new approaches to disease treatment and diagnosis of Mycobacterium tuberculosis. In 1998, Cole et al. reported the complete genome sequence of Mycobacterium tuberculosis. The new information will provide us the knowledge and understanding of the biology of Mycobacterium tuberculosis. Further, it will provide us new conception of diagnosis and treatment of the disease. Four topics were selected in this symposium. Dr. Iinuma reviewed and prospected the clinical utility of nucleic acid amplification methods of Mycobacterium tuberculosis. Dr. Suzuki reviewed the molecular mechanism of acquired resistance to anti-TB drugs and reported the early detection of genetic mutation by new designed DNA tip method. Dr. Takahashi reviewed the method of molecular epidemiology and genetic elements as a tool for strain differentiation of tuberculosis. Dr. Mizuguchi interpreted the essential feature of mycobacterial genome maps, and genes and their biological activity. He also reviewed the importance and the utility of the complete genome sequence of tuberculosis in association with pathogenecity. These topics were summarized in this report, based on the symposium of "Molecular genetic approaches to Mycobacterium tuberculosis" in the 75th annual meeting of the Japanese Society for Tuberculosis. PMID- 11201142 TI - [Estimating cost functions of cancer screening programs provided by municipalities]. AB - OBJECTIVE: To estimate cost functions of cancer screening programs for stomach, lung, colorectal, cervical, and breast cancers provided by municipalities and to describe the relationship between the costs and the scale of cancer screening programs. METHODS: Subjects were all the municipalities in Japan. Questionnaires were sent to 3,182 subjects and 1,860 responses were received. Data obtained from questionnaires were the number of persons screened and the total cost of each program in the 1998 fiscal year. A cost function of each program was specified as a linear model, a power model, and a cubic model, and the fitness of each model was estimated. RESULTS: Long-run cost functions of all the cancer screening programs allowed better explanation of the relationship between the number of persons screened and the total cost than short-run cost functions. The average costs of stomach, colorectal, and cervical cancer screening programs increased and the average cost of the lung cancer screening program decreased, as the number of persons screened increased. The cost function of the breast cancer screening program could not be identified. CONCLUSIONS: It is necessary to estimate not only cost functions but also production functions of cancer screening programs using the data related to products, costs, and factors of production to evaluate the efficiency of cancer screening programs. PMID- 11201143 TI - [Some discussion on why WHO definition of health has not been revised]. PMID- 11201144 TI - [Application of cost-effectiveness analysis of health care interventions in developing countries. A case study in Mauritius]. AB - OBJECTIVE: Cost-effectiveness analysis is a tool to help inform the decision maker of efficient allocation of scarce health care resources and its application has increased in developing countries during the past decade. There are, however, a variety of different approaches used to calculate cost-effectiveness ratios, given the range and the controversies surrounding the use of some components of total cost, depending on the constraints faced by various decision-making bodies. This study is an investigation of cost-effectiveness of both currently delivered and prospective health interventions in Mauritius to set priorities and assess allocative efficiency by taking into account such constraints. METHODS: Resource use and unit cost data were collected from the representative health facilities and the Ministry of Health to estimate costs of each health intervention per person. Effectiveness of each intervention was estimated from the results of the national burden of disease study and the efficacy database compiled for this exercise. Several types of cost-effectiveness were calculated for each intervention according to its characteristics and the constraints imposed by the existing infrastructures and other health interventions. RESULTS: Cost effectiveness ratios with and without the decision maker's constraints differed significantly. Infrastructure-constrained average cost-effectiveness of thirteen currently delivered and twenty one prospective interventions ranged from $127 to $92,949 and from $77 to $66,302 per DALY averted, respectively. Incremental cost effectiveness of the prospective interventions was from $83 to $70,553. Among the currently delivered interventions, those for perinatal disorders, mental illness, and ischemic heart disease were particularly less cost-effective than the prospective interventions. Sensitivity analysis of both effectiveness and discount rates did not change the cost-effectiveness ranking significantly. CONCLUSION: The present study showed that cost-effectiveness ratios differ significantly depending on the decision maker's constraints and that an interpretation of each cost-effectiveness study should be made with great caution when implementing its results in practice. Both average cost-effectiveness of the currently delivered interventions and incremental cost-effectiveness of the prospective interventions suggest that there is an allocative inefficiency among the currently delivered health interventions in Mauritius and a possibility of enhancing allocative efficiency through introducing alternative interventions. PMID- 11201145 TI - [Validity of the infectious disease surveillance system on comparison of nationwide surveys of Kawasaki disease during a 10 year period]. AB - PURPOSE: To verify the validity of the infectious disease surveillance system in Japan using data for Kawasaki disease. MATERIALS AND METHODS: Data from nationwide surveys of Kawasaki disease conducted by the Kawasaki Disease Research Committee every two years over the 10 years (120 months) from 1989 through 1998 were used to calculate a gold standard. Then, the monthly numbers of patients with Kawasaki disease reported by monitoring hospitals (about 550 hospitals) to the surveillance system were compared with this gold standard. Each of the monthly numbers was standardized by division by the average monthly number of patients over the 120 months. Observations for 3 districts (eastern part, central part, and western part of Japan) were conducted as well as for the whole country. RESULTS: The number of patients reported to the surveillance system varied more widely than in the nationwide survey, but directions of the fluctuations were similar to the chronologic changes in nationwide numbers. Accordingly, a high correlation coefficient value of 0.794 was obtained (p < 0.01). Similar results were observed in all 3 districts. The correlation coefficients were 0.709 for the eastern part, 0.561 for the central part, and 0.712 for the western part, respectively, and all of them were of statistically significant. CONCLUSION: Changes in number of patients with Kawasaki disease reported to the surveillance system resemble the pattern of the gold standard. PMID- 11201146 TI - [Facsimile and Internet for provisions of information about prevalence of infectious disease to primary care physicians]. AB - PURPOSES: In Japan, surveillance of infectious disease has been enforced since 1981. Facsimile and Internet have become popularized recently, and in the present study we investigated the means of obtaining related information primary care physicians. METHODS: Questionnaires were mailed to 117 hospitals and 1,162 clinics in Mie prefecture. Responses from 76 hospitals (65.0%) and 689 (59.3%) clinics were received. RESULTS: Approximately 80 percent of primary care physicians obtain information about this survey by bulletin. They desire to obtain the latest information to aid diagnosis. More than 90 percent of them have facsimile, and 37.6 percent of them have access to Internet. The majority of them prefer to receive information by facsimile. CONCLUSION: Therefore, facsimile is the most powerful media for such information transfer at present. PMID- 11201147 TI - [A study on resource based relative values for visiting nursing services]. AB - PURPOSE: The purpose of this study was to investigate the resource based relative values of visiting nursing services, and to analyze the relationships between the relative values and the dimensions of nursing service(time, mental effort and physical effort). METHODS: We interviewed nurses at 20 Home-visit nursing care stations (HVNCS) in the Metropolitan area using the resource based relative value questionnaires. We asked nurses about relative values of "Total Work", and also measured relative weight of 3 dimensions of nursing services. Total Work was defined as comprehensive evaluation of nursing services, with careful consideration of intensity as well as duration. With the dependent variable as Total Work and independent variables as the 3 dimensions, multiple regression analyses were carried out. Furthermore we examined the degree of influence on Total Work by service type and individual respondent. To examine the validity of the results, we timed nursing services and compared the measured time with the answered time. RESULTS: The 107 respondents were all female and their average age was 36.6 years old. They had HVNCS experience of 2.2 years and 95.3% nurses had experience of hospital nursing. "Total Work" and 3 dimension scores were standardized using common logarithms. "Total Work" of every service significantly differed among service types. The 3 dimensions explained 54.6% of Total Work in the multiple regression analysis. Service type explained 3.3% of Total Work. Individual respondent explained 16.0% of Total Work. Answered time and measured time were not significantly different with nursing services. CONCLUSIONS: Although Total Work was somewhat influenced by individual respondent, most of variation was explained by 3 dimensions. Thus, it could be concluded that Total Work is an index of nursing resource input. A further investigation about influence of patients' condition on Total Work is necessary in the future. PMID- 11201148 TI - [Development of a scale for subjective QOL common to patients with intractable diseases]. AB - OBJECTIVE: We have developed a scale for evaluating subjective quality of life (QOL) common to patients with intractable diseases. SUBJECTS: Two-hundred and forty-seven outpatients of housebound patients from 7 collaborating hospitals or institutions participated in preliminary surveys. The patients were diagnosed with one of 14 diseases targeted by the Ministry of Health and Welfare's Specific Disease Treatment Research Project. Two-hundred and fifty-seven outpatients or housebound patients of 8 collaborating hospitals or institutions participated in a second survey that targeted 15 diseases. METHODS: The concept of subjective QOL was examined, and a favorable subjective QOL score was defied as "a state in which patients accept their current condition and possess a high level of morale with no signs of anxiety, despite the presence of their disease". Sixty-six items were then identified and included in a preliminary survey. Three preliminary surveys and a second survey were then conducted. A final scale for the items was then decided, and the items were assessed for their reliability and validity. RESULTS: Nine items reflecting two factors, "acceptance" and "morale", were selected and assessed for their reliability and validity as follows: 1) The response of subjects who accepted their illness yet possessed a high level of morale showed a good fit with the proposed scale (Adjusted Goodness of Fit Index = 0.925). 2) The confidence coefficient of the re-test method for subjective QOL scale scores was r = 0.78 (95% con idence interval: 0.72-0.83; n = 226) nd the alpha coefficient was 0.822, indicating a high level of reliability. 3) A strong negative correlation (r = -0.76, 95% confidence interval: -0.82 to -0.69; n = 178) was found between the subjective QOL scale scores and self-rating depression scale (SDS) scores, and a moderately positive correlation (r = 0.35, 95% confidence interval: 0.23-0.46; n = 238) was found between the subjective QOL scale scores and activities of daily living (ADL) scores. 4) No statistically significant differences were observed in the distribution of subjective QOL scale scores when analyzed according to sex, age group, disease, or duration of illness. CONCLUSIONS: We have developed a scale consisting of 9 items for determining the subjective QOL of patients with intractable diseases. The scale was confirmed to properly reflect our concept of subjective QOL, which consists of two factors: "acceptance" and "morale" The scale was also confirmed to be stable and highly reliable. PMID- 11201149 TI - [Successful allogeneic bone marrow transplantation following fungal liver abscess treatment in a patient with chronic myeloid leukemia in blastic crisis]. AB - A 40-year-old man was diagnosed as having chronic myeloid leukemia (CML) in December 1990 and received busulfan and hydroxyurea. He developed myeloid blast crisis in February 1996. After DCMP combination chemotherapy, his disease reverted to chronic phase, but right hypochondrial pain developed and low-grade fever persisted. Abdominal CT scan revealed multiple low-density areas in the liver, suggestive of abscess formation. Grocott staining of a liver biopsy sample revealed granuloma and fungus. The patient was treated with intravenous amphotericin B (AMPH-B) without success. AMPH-B was then administered via a catheter placed in the portal vein on January 6, 1997, and an additional catheter placed in the hepatic artery on March 28. AMPH-B was administered through both catheters for more than two months, but later substituted by fluconazole because of renal impairment. On September 10, allogeneic bone marrow transplantation from the patient's HLA-identical brother was performed, despite persistence of the abnormal CT findings. Acute grade III GVHD developed, but there was no evidence of reactivation of the liver abscesses. This case demonstrates that a prior fungal liver abscess is not an absolute contraindication for BMT if prophylactic antifungal drugs are administered and careful observation is conducted. PMID- 11201151 TI - [Angioimmunoblastic T-cell lymphoma associated with hemophagocytic syndrome at onset and relapse]. AB - A 66-year-old woman was admitted with high fever, systemic lymphadenopathy, hepatosplenomegaly and pancytopenia. Bone marrow aspiration showed infiltration of atypical lymphoid cells and hemophagocytic histiocytes. The findings of lymph node biopsy were compatible with angioimmunoblastic T-cell lymphoma (AILD). A diagnosis of lymphoma-associated hemophagocytic syndrome (LAHS) was made. Treatment with the THP-COP regimen achieved clinical remission except for mild splenomegaly, but relapse of LAHS was confirmed two years after diagnosis. The patient's condition deteriorated rapidly, and she died of multi-organ failure one month later. Autopsy revealed extended, diffuse infiltration of lymphoma cells in almost all organs. Numerous macrophages showing phagocytosis of erythrocytes and nucleated cells were found in the adrenal glands, lungs, bone marrow, spleen and liver. Epstein-Barr virus genomes were not detected by in situ hybridization, but cytotoxic molecules were immunostained with TIA-1 and granzyme B in the lymphoma cells. Elevated serum levels of sIL-2R, IFN-gamma, IL-6 and M-CSF were found at the onset and relapse of lymphoma. Overproduction of these cytokines was considered to have contributed to the pathogenesis of HPS. PMID- 11201150 TI - [Rapidly progressive fibrosis and increased CD68-positive cells in the bone marrow at the terminal stage of adult T-cell leukemia accompanied by polycythemia vera]. AB - We report a case of adult T-cell leukemia (ATL) accompanied by polycythemia vera (PV) in which rapid development of myelofibrosis and clinical features of hemophagocytic syndrome (HPS) were observed at the terminal stage. The patient, a 53-year-old man who was born in Oita Prefecture, Japan, was diagnosed as having PV in 1996. He had undergone venesection but had not received any chemotherapy. In June 1997, he showed systemic lymphadenopathy with positivity for serum HTLV-1 antibody (x 10,240). Pathological findings and Southern blotting analysis for detection of monoclonal integration of HTLV-1 provirus DNA in a lymph node biopsy sample revealed that he also had acute-type ATL. Although several courses of chemotherapy were transiently effective, high fever, pancytopenia, increased serum LDH, hypoproteinemia and hyperferritinemia appeared, all of which were compatible with the clinical features of HPS. In addition, cytomegalovirus infection became evident. He died of multiple organ failure with rapid progression of myelofibrosis in May 1998. Detection of both increased CD68 positive histiocytes by immunohistochemistry and iron-stained phagocytic cells in marrow biopsy specimens appeared to be helpful for diagnosis of HPS in this patient, whose marrow showed myelofibrosis with hypocellularity. PMID- 11201152 TI - [Development of Hodgkin's disease four years after autologous peripheral blood stem cell transplantation for multiple myeloma]. AB - We report a case of Hodgkin's disease that developed 4 years after autologous peripheral blood stem cell transplantation (PBSCT). The patient, a 67-year-old Japanese male, underwent PBSCT for multiple myeloma (IgA-lambda type) under a conditioning regimen of carboplatin, etoposide and cyclophosphamide in June 1994 and obtained partial remission. In January 1995, he underwent a second PBSCT under a conditioning regimen of high-dose melphalan and obtained complete remission. In December 1998, he noticed swelling of the left cervical lymph nodes, and Hodgkin's disease of the mixed cellularity subtype was diagnosed from a lymph node biopsy sample. Immunohistochemistry studies showed that the Hodgkin's and Reed-Sternberg cells were CD30-positive. In situ hybridization using EBER probes showed that these cells expressed EBER RNA transcripts, indicating that the tumor was associated with Epstein-Barr virus. One noteworthy feature was the absence of both M-component in the serum and urine, as revealed by immunoelectrofixation, and plasmacytosis in the bone marrow, which would have indicated relapse of the multiple myeloma. After chemotherapy with MOPP and ABVD, the Hodgkin's disease was eradicated and the patient obtained complete remission in May 1999. PMID- 11201153 TI - [Occurrence of angioimmunoblastic T-cell lymphoma six months after onset of Lyme disease]. AB - A 68-year-old man, who had suffered a tick bite one week previously, consulted his home doctor because of fever and an erythematous rash around the bite scar. He underwent a skin biopsy, and Borrelia garinii was detected, from which Lyme disease was diagnosed. He received amoxicillin for two weeks and his symptoms disappeared. After 6 months he noticed swelling of his cervical, axillary and inguinal lymph nodes. A biopsy sample was taken from a left cervical lymph node, and this revealed angioimmunoblastic T-cell lymphoma. The patient achieved a complete remission after chemotherapy. The relationship between Lyme disease and lymphoma is discussed. PMID- 11201155 TI - [Angioimmunoblastic T-cell lymphoma presenting with rapidly increasing biclonal gammopathy]. AB - A 59-year-old man was admitted to our hospital with high fever and dysphagia. Physical examination revealed a lingual tumor and swelling of the cervical and inguinal lymph nodes. A lymph node biopsy specimen revealed that the normal nodal architecture had been obliterated by infiltration of small, intermediate, and large pale lymphocytes. Arborous branching of high endothelial venules was also observed. Southern blotting analysis showed rearrangement of the T-cell receptor beta gene. A diagnosis of angioimmunoblastic T-cell lymphoma was made. Serial serum protein fractionation analysis showed rapidly increasing M-protein. Immunofixation electrophoresis indicated specific bands for IgG kappa and IgM lambda, confirming the presence of biclonal gammopathy. Biclonal gammopathy has rarely been reported in patients with angioimmunoblastic T-cell lymphoma. The relationship between the occurrence of biclonal gammopathy and the possible role of HHV-6, HHV-8 and EBV is discussed. PMID- 11201154 TI - [Nonmyeloablative stem cell transplantation with low-dose total body irradiation (200 cGy) for a 55-year-old woman with acute lymphoblastic leukemia]. AB - We describe a 55-year-old woman with acute lymphoblastic leukemia (ALL) in the first remission who underwent nonmyeloablative stem cell transplantation with conditioning consisting of low-dose total body irradiation and postgrafting cyclosporine and mycophenolate mofetil. Myelosuppression was mild, but on day 28 her bone marrow showed 8.8% lymphoblasts. We withdrew the cyclosporine, but the patient developed grade 2 acute GVHD and eosinophilia. The proportion of bone marrow lymphoblasts decreased transiently to 1.0% on day 40, but later increased again and the patient died on day 85. Application of this approach to patients with ALL needs to be examined on a large scale. PMID- 11201156 TI - [Idiopathic hyperammonemia following allogeneic bone marrow transplantation for refractory lymphoma]. AB - Idiopathic hyperammonemia (IHA) is a rare but serious complication of stem cell transplantation. We report a patient with immunoblastic lymphoadenopathy-like T cell lymphoma who developed IHA 10 days after allogeneic bone marrow transplantation from an HLA-matched unrelated donor. Despite intensive supportive care, the patient died due to this metabolic disorder two days later. Being mindful of the possibility of IHA in patients who develop confusion and respiratory alkalosis soon after stem cell transplantation would allow earlier treatment and might improve the chance of survival. PMID- 11201157 TI - [The G protein-coupled protease receptor PAR (protease-activated receptor) as a novel target for drug development]. AB - The protease-activated receptor (PAR) is the family of G protein-coupled, seven transmembrane domain receptors, currently consisting of four members, PARs 1-4. The activation of PARs occurs by proteolytic unmasking of the N-terminal cryptic receptor-activating tethered ligand. In the past decade since the cloning of PAR 1, physiological roles that PARs play have been gradually understood and are now considered extremely extensive and important. This review describes physiological and/or pathophysiological roles of PARs in the circulatory, digestive, respiratory and central nervous systems, on the basis of our works and of those achieved by other research groups. The future perspective of studies on PARs is also discussed, focusing on the possibility of clinical application of PAR targeted drugs. PMID- 11201158 TI - Progress and problems in the prescribing/dispensing split and "divided package sales" by wholesalers. AB - Given the rapid progress of the prescribing/dispensing split, the ability of pharmacies to obtain and stock a small quantity of pharmaceuticals is seen as essential. Toho Yakuhin's experience in "divided package sales" (wholesalers open an original package supplied by the manufacturer and sell only a part of the contents) shows that the number of orders and sales amount, and the number of pharmacies ordering in sales have remarkably increased. One or two kinds of pharmaceuticals were ordered in 73% cases, and one or two units in about 50%. This implies that "divided package sales" are utilized to obtain rarely prescribed drugs. On the other hand, five or more kinds of pharmaceuticals were ordered in 10% of cases, and ten or more units in 17%. "Divided package sales" were more used for low-price drugs. These indicated that "divided package sales" seemed to be looked upon by pharmacies as a means of obtaining a small quantity of pharmaceuticals, and seemed to be used not only in an emergency but also routinely. There are several problems for wholesalers in operating "divided package sales", such as frequent delivery, delivery cost and information supply. Pharmacies should obtain a small quantity of pharmaceuticals by the routine delivery and should share the delivery cost. Pharmaceutical manufacturers' cooperation in printing necessary information on each immediate container will be useful. Though there could be alternative ways of obtaining a small quantity of pharmaceuticals, all of them have the matter of delivery. We believe "divided package sales" will contribute to this situation. PMID- 11201159 TI - [Antioxidative effects of fluvastatin, and its major metabolites [II]]. AB - We investigated the antioxidative effects of fluvastatin (FV or (+/-)-FV), each enantiomer ((+)-FV, (-)-FV) and its major metabolites on lipid peroxidation using rat and human liver microsomes. The extent of NADPH induced microsomal (Ms) lipid peroxidation was determined by thiobarbituric acid (TBA) assay. The antioxidative effect of each compound was shown as the percentage of inhibition on the formation of TBA reactive substance (TBARS) against vehicle control. The antioxidative effects of alpha-tocopherol (Toc), a potent antioxidative vitamin, probucol (PR), a potent antioxidative drug, pravastatin (PV) and simvastatin (SV), HMG-CoA reductase inhibitors, were also tested. The (+/-)-FV inhibit the formation of TBARS by 40 to 70% depending on Ms concentrations. The antioxidative effects of PR and TOC were comparable to those of FV. The inhibitory effects of PV and SV on the formation of TBARS were less potent than (+/-)-FV, PR and TOC. (+)-FV, (-)-FV, and (+/-)-FV inhibited the formation of TBARS by approximately 50% using rat hepatic microsomes. The antioxidative effects of (+)-FV was comparable to that of (-)-FV using human hepatic microsomes. These results indicated that the antioxidative effects of (+)-FV were comparable to those of ( )-FV, although the HMG-CoA reductase inhibitory activity of (+)-FV was 30-fold higher than that of (-)-FV. PMID- 11201160 TI - [Functional analysis of phospholipase A2 receptor by gene knockout studies]. AB - Phospholipase A2 receptor (PLA2R) is a type I transmembrane glycoprotein related to the C-type animal lectin family and mediates a variety of biological responses elicited by group IB secretory phospholipase A2 (sPLA2-IB). In the present study, we have shown the evidence that a novel type of sPLA2, sPLA2-X, also acts as one of the high-affinity ligands for mouse PLA2R. We then generated PLA2R-deficient mice and found that the knockout mice exhibited the resistance to an endotoxic shock with reduced plasma levels of proinflammatory cytokines, such as TNF-alpha and IL-1 beta. In situ hybridization analysis revealed that the expression of PLA2R transcript was markedly enhanced in type II alveolar epithelial cells and a subset of splenic lymphocytes in accordance with the elevated expression of sPLA2 IB and TNF-alpha mRNAs during endotoxic shock. In addition, the elevated expression level of TNF-alpha transcript was significantly reduced by the deficiency of PLA2R, suggesting that PLA2R plays a role in the regulation of TNF alpha expression in these cell types. We then synthesized a specific sPLA2 inhibitor, indoxam, which blocked the binding of sPLA2-IB and X to PLA2R. Indoxam was found to suppress the elevation of the plasma level of TNF-alpha and prolonged the survival of endotoxin-challenged mice. The inhibitory effects of indoxam were abolished by the deficiency of PLA2R, demonstrating the involvement of PLA2R in the progression of endotoxic shock. We also detected and characterized a soluble form of PLA2R protein in the plasma of mouse with anti PLA2R antibody, and showed its potential role as an endogenous sPLA2 inhibitor. Taken together, a series of studies with PLA2R-knockout mice have elucidated a critical role of PLA2R in the regulation of the development of endotoxic shock. PMID- 11201161 TI - [A study for functions of prostaglandin E receptor EP4 subtype by analysing knockout mice]. AB - The physiological role of the prostaglandin (PG) E2 receptor EP4 subtype was investigated by the generation of EP4-deficient mice by gene targeting. Loss of the EP4 receptor was not lethal in utero, but most EP4 (-/-) neonates became pale and lethargic approximately 24 h after birth, and died within 72 h. Less than 5% of the EP4 (-/-) mice survived and grew normally more than a year. Marked congestion in the pulmonary capillaries were observed before death, suggesting that EP4 (-/-) neonates had left-sided heart failure. Histological examination revealed that the ductus arteriosus in dead neonates remained open, while it was partially closed in the survivors. In situ hybridization study showed that EP4 mRNA was strongly expressed in the ductus. The treatment of indomethacin, an inhibitor of PG synthesis, on wild-type fetus induced constriction of ductus arteriosus, while the ductus in EP4 (-/-) fetus was insensitive to indomethacin. These results suggest that neonatal death is at least partly due to patent ductus arteriosus, and that the EP4 receptor plays a role in the regulation of the patency of this vessel. They also indicate that the normal function of the EP4 receptor is essential in neonatal adaptation of the circulatory system. PMID- 11201162 TI - [Software development for calculation of molecular surface area and its application to hydrophobic interaction]. AB - A novel method of calculating the water-accessible molecular surface area from the number of points generated on the molecular surface was developed. This method yielded a molecular surface area with high accuracy and speed. The molecular surface area of lecithin shows an excellent linear correlation with the logarithm of the critical micelle concentration for many lecithins having different acyl chains. The solution structure of oxyphenonium bromide estimated from the molecular surface area approach was close to that obtained from NMR. Furthermore, the change of molecular surface area, delta S(HG), with docking of host and guest was defined and its calculation method was developed. Because both the host and the guest generally consist of hydrophilic and hydrophobic atomic groups, delta S(HG) was divided into such four terms as delta Soo(HG), delta Sow(HG), delta Swo(HG), and delta Sww(HG). For instance, delta Soo(HG) is the decrease in surface area with contact between the hydrophobic surfaces of the host and the guest. When the guest molecule was moved along the symmetry axis of cyclodextrin (CyD), the structure of a complex having the maximum value of delta Soo(HG) corresponds with the crystal structure. The solution structures of several inclusion systems were predicted by this method. For various systems including alpha-CyD, beta-CyD, gamma-CyD, and aromatic and aliphatic guests, the maximum values of delta Soo(HG) showed a good correlation with the logarithms of the binding constants. This relationship will be used for the prediction of the binding constants for CyD and other host-guest systems. PMID- 11201163 TI - [Nitrogen pyramidal amides and related compounds]. AB - A planar amide bond is a fundamental linkage in the structures of peptides and proteins. The rigid planarity of the amide linkage, due to a conjugation between carbonyl and amine groups, may be requisite for encoded protein folding and many other biological processes. Non-planar amides in the ground state will decode the significance of the planarity and rigidity of the amide linkage. We show here that simple amides of 7-azabicyclo[2.2.1]heptane, free from steric bias, including parent N-benzoyl 7-azabicyclo[2.2.1]heptane, are nitrogen-pyramidal amides in the crystalline state. We can suggest that pyramidalized amide nitrogen is a general feature and intrinsic to the 7-azabicyclo[2.2.1]heptane motif. Low rotational barriers of the amide C-N bond in a series of N-benzoyl amides of 7 azabicyclo[2.2.1]heptane, compared to monocyclic amides, may imply that ground state nitrogen pyramidalization of the former amides also exist in solution. The 7-azabicyclo[2.2.1]heptane motif also favors nitrogen pyramidalization of sulfonamides and N-nitrosoamines, which can lead to pharmacophores after appropriate modification. PMID- 11201164 TI - Clinical characteristics of asthmatic patients prescribed various beta-agonist metered-dose inhalers at Yamagata University Hospital. AB - To determine the prescription characteristics of beta-agonist metered-dose inhalers (MDI), we retrospectively investigated all prescriptions containing one of five types of beta-agonist MDIs available at Yamagata University Hospital in 1997, as well as patients' characteristics. The total number of asthmatic patients was 225 (age, 11-79, mean, 47.2) in 1997. Fenoterol MDI was prescribed to patients who visited the hospital at regular periods and had more severe asthma. Isoprenaline MDI also was not prescribed for first-time patients. Patients who were prescribed tulobuterol MDI had mild or moderate asthma and some of them were only occasional or first-time visitors. Salbutamol and procaterol MDIs were also prescribed for first-time patients; however, tulobuterol MDI was the most frequently prescribed for first-time patients. Patients prescribed fenoterol and isoprenaline MDIs had adequate knowledge of proper asthma management, because sufficient information had been provided about the use of MDIs in the past. Patients prescribed tulobuterol MDI should be provided with detailed instructions because they had little knowledge of handling MDIs and self management of asthma as many of them were first or intermittent visitors. Patients prescribed salbutamol or procaterol MDIs should be evaluated regarding their past medications and some of them should be instructed regarding the use of the MDI. Although these clinical aspects might be applicable only to our hospital, the same or other prescription patterns will be found in other hospitals and/or by other physicians. Adequate instructions to individual patients who are prescribed a particular beta-agonist MDI should be provided by the medical staff, especially to outpatients, to reduce hospitalization and death from asthma. PMID- 11201165 TI - [Strain-, sex- and species-related differences of acetohexamide reductase and 20 beta-hydroxysteroid dehydrogenase activities in liver microsomes of experimental animals]. AB - We examined physiological and genetic factors affecting acetohexamide reductase (AHR) and 20 beta-hydroxysteroid dehydrogenase (20 beta-HSD) activities in liver microsomes of experimental animals. Pronounced strain-related differences were found in both activities of AHR and 20 beta-HSD present in liver microsomes of male rats. Among rat strains tested in this study, even though a Wistar-Imamichi (WIM) rat strain was taken to lack AHR activity, it exhibited a significant 20 beta-HSD activity. These findings appeared to be in conflict with our conclusion reported so far, which AHR and 20 beta-HSD present in liver microsomes of male rats are identical enzymes. Thus the reason for this discrepancy was discussed. Furthermore, AHR and 20 beta-HSD activities were little or not observed in liver microsomes of female rats or male experimental animals other than the rat, indicating the existence of sex- and species-related differences in these two enzyme activities. PMID- 11201166 TI - [In vitro and in vivo study of regulation mechanisms of type I interleukin-1 receptor]. AB - Interleukin 1 (IL-1) is one of the inflammatory cytokines, which plays a pivotal role in both host defense and homeostasis. Its signal is transduced by type I IL 1 receptor (IL-1RI). This report gives an insight into the regulatory mechanism of IL-1RI in both in vitro and in vivo. IL-1 up-regulates IL-1RI through prostaglandin E2 (PGE2) production on human fibroblasts. However, in the presence of indomethacin, IL-1 down-regulates the receptor by destabilizing IL-1 receptor mRNA. Type I and type II interferons (IFNs) up-regulate the expression of IL-1RI. This up-regulation leads to the increasing susceptibility of IL-1RI to IL-1, as the DNA binding of IL-1-induced NF-kappa B and the production of IL-1-induced IL 6 from the fibroblasts are augmented by pretreatment with IFNs. On the other hand, the expression of cell surface IL-1RI is inhibited by tyrosine kinase inhibitors, herbimycin and genistein, resulting in reduction of the kinase activity of IRAK (IL-1 receptor associated kinase) and IL-1-induced IL-6 production from the fibroblasts. Lipopolysaccharide (LPS) augments the expression of IL-1RI mRNA and cell surface molecule in the hepatocytes of mice in vivo, and the augmentation is mediated by the interaction of IL-1, IL-6, and of glucocorticoid (GC). When hepatocytes were pretreated with dexamethasone (Dex) and IL-6, the activation of IRAK was augmented in response to IL-1, indicating that IL-1 signaling is also up-regulated. In addition, IL-1 treatment ather combined administration of Dex and IL-6 into mice markedly increased the serum level of serum amyloid A. These data suggest that the expression of IL-1RI is regulated by inflammatory cytokines, PGE2, GC and LPS in vitro and in vivo. This study shows that the biological activity of IL-1 can be controlled by regulating the expression of IL-1RI, and therefore proposes the use of pharmaceutical drugs for the regulation of cytokine expression. PMID- 11201167 TI - [Effect of selenium on serum, hepatic and lipoprotein lipids concentration in rats fed on a high-cholesterol diet]. AB - The effects of Selenium (Se) on lipid metabolism was studied in male Wistar rats which were fed a high-cholesterol diet (HCD) containing 1%(w/w) cholesterol and 0.5%(w/w) cholic acid for 10 weeks. Se was orally administered at daily doses of 0.173 mg/kg in HCD into the test rats for 10 weeks. As compared with control groups, Se/HCD suppressed the amounts of triglyceride (TG), total cholesterol (CH) and free fatty acid in the serum. Se/HCD also decreased the amounts of low density lipoprotein cholesterol (LDL-C) in the serum. Further-more, Se/HCD inhibited the amount of liver TG and CH. The activity of fatty acid synthetase in the HCD fed group was higher than in the Se/HCD fed group. These results suggest that Se may have recuperative effects for hypercholesterolemia. PMID- 11201168 TI - [Sensitization and crossreaction of simple coumarins]. AB - The contact sensitization of 11 simple coumarins was examined by subcutaneous sensitizing of guinea pigs, and the structure-activity relationship and cross reactivity were investigated. Esculetin, 4-methylesculetin, and dephnetin were found to be strong sensitizers, and 4-hydroxy-coumarin to be a moderate sensitizer. Other simple coumarins tested had a weak sensitivity to mild sensitizers. The results suggest that the introduction of hydroxy group, especially adjacent substitution at the 6, 7, and 8 positions of the coumarin ring with two hydroxy groups, may play an important role in exhibiting the contact sensitization activity. The cross-reactivity was observed between esculetin and 4-methylesculetin, esculin or isoscoporetin, and also between daphnetin and 4-methylumbelliferone or umbelliferone, although there was no mutual cross-reactivity between esculetin and daphnetin. It is interesting to note that guinea pigs, which had a weak sensitivity to umbelliferone, showed a strong cross-reactivity to daphnetin, while those, which had a weak sensitivity to daphnetin, showed a weak cross-reactivity to umbelliferone. It is assumed that a skin-protein conjugation at 5 or 6 positions of the coumarin ring is important to elicit the cross-reactivity of esculetin or daphnetin groups. PMID- 11201169 TI - A search for chemical agents causing human cancer--lessons learned from rodent carcinogenicity studies. AB - Analysis of classical life-time rodent bioassays conducted over the past 20 years under conditions of Good Laboratory Practice Regulations has led to an improved understanding of possible factors involved in oncogenesis in humans. Improvements in study design coupled with more detailed pathological examinations have led to new insights whereby neoplastic processes can be more clearly identified and understood with confidence in animal models. Improvements in the ability to identify potential risks through continued animal testing combined with incorporation of advances in genetics and molecular biology in elucidating mechanistic factors will greatly facilitate future research efforts to identify causative agents of human cancer. A great deal of attention will have to be paid to the concept of threshold doses and exposure levels that may be required to achieve preneoplastic conditions or the induction of carcinogenic processes. Future concerns of hazards, risk assessment and the evaluation of carcinogenic potential will involve an amalgamation and understanding of radiological and biological events, especially those of carcinogenic microorganisms, the effects of food and air borne carcinogens, effects of pollution, exposure to xenobiotics and imbalances and disruption of normal biologic functioning of endogenous physiologically active substances, to achieve a better understanding and ultimate prevention of human cancer. PMID- 11201170 TI - No toxicity caused by organ accumulation of CPT-11 on multiple injections under clinical regimens in rats. AB - We investigated the accumulation of CPT-11 and its metabolite (SN-38) in various organs and toxicities on multiple injections of CPT-11 under clinical regimens in SD rats. CPT-11 (16.7 mg/kg equivalent to 100 mg/m2) was administered intravenously by a single injection, or by multiple injections in 1 course (once a week for three consecutive weeks) or 3 courses (1 course repeated 3 times at intervals of 2 weeks). There was no tendency for CPT-11 and SN-38 to accumulate in any organs regardless of the number of injections. Treatment-related changes were not observed in the general condition, body weight, hematology, biochemistry, and organ weights. Histopathological changes induced by CPT-11 were not persistent and the rats made a rapid recovery after the administrations. From these results, it is suggested that there is no toxicity caused by accumulation of CPT-11 and its active metabolite, SN-38, in organs under clinical regimens in rats. PMID- 11201171 TI - Evaluation of a 5-day Hershberger assay using young mature male rats: methyltestosterone and p,p'-DDE, but not fenitrothion, exhibited androgenic or antiandrogenic activity in vivo. AB - A 5-day Hershberger assay using young mature male rats to detect compounds interfering with androgen receptor (AR)-mediated mechanisms was evaluated for ability to identify p,p'-DDE (a weak AR antagonist) and methyltestosterone (MT, an AR agonist). Fenitrothion, an organophosphate pesticide, was also evaluated in this validated assay. Castrated male Crj:CD(SD)IGS rats (1 week after castration, 11 weeks of age) were subjected to experiments. To determine a suitable value of testosterone propionate (TP) as a reference androgen for detection of antiandrogenic chemicals, castrated male rats were treated daily with TP (0, 0.06, 0.25, 1, 4, or 16 mg/kg/day, s.c.). TP produced increases in weights of ventral prostate, seminal vesicles and levator ani plus bulbocavernosus muscles. Serum androgen level measured by RIA kit (mostly TP) were elevated in a dose related manner, while the weights of organs with 1 mg/kg/day of TP were nearly equivalent to the maximum responses (i.e., sub-maximal). One hundred mg/kg/day of p,p'-DDE significantly attenuated TP 0.1 mg/kg-induced increases in weights of seminal vesicles and muscles, and TP 1 mg/kg-induced increases in weights of ventral prostate, seminal vesicles and muscles, but did not affect the weight of these organs in either TP 16 mg/kg-treated or intact rats, demonstrating that the dose range of 0.1-1 mg/kg TP is suitable for reference androgen. Oral treatment with 100 mg/kg of MT increased the weights of ventral prostate, seminal vesicles and muscles as strongly as did subcutaneous injection of 1 mg/kg of TP. These findings demonstrate that the 5-day Hershberger assay using young mature as well as immature male rats is a sensitive and valid short-term screening method for the detection of chemicals interfering with AR-mediated mechanisms. To determine whether fenitrothion interferes with AR-mediated mechanisms in vivo, fenitrothion (0, 0.75, 1.5 or 3 mg/kg/day) was administered by gavage for 5 days to castrated rats for androgenicity, or to castrated rats treated with 1 mg/kg TP for antiandrogenicity. Treatment with fenitrothion had no adverse effects on clinical signs, body weight, or liver or kidney weights, but cholinesterase activities in the brain and erythrocytes were significantly suppressed by fenitrothion to, respectively, 77-81% and 66-67% of control levels. In the antiandrogenicity experiment, serum androgen levels of TP-treated, castrated rats did not differ among groups. Treatment with 100 mg/kg of p,p'-DDE as a positive control again significantly attenuated TP-induced increases in weights of the ventral prostate and seminal vesicles, while fenitrothion had no effect on the weights of any organs. In the androgenicity experiment, treatment with 100 mg/kg of MT significantly increased weights of ventral prostate, seminal vesicles and muscles, but fenitrothion had no effects on the weights of any of these organs. These findings yield no evidence that fenitrothion interferes with AR-mediated mechanisms in vivo, consistent with the result of several toxicological bioassays. PMID- 11201172 TI - Influences of alkaline ionized water on milk electrolyte concentrations in maternal rats. AB - We previously reported that body weight on day 14 after birth in male offspring of rats given alkaline ionized water (AKW) was significantly heavier than that in offspring of rats given tap water (TPW), but no significant difference was noted in milk yield and in suckled milk volume between the two groups. Additionally, the offspring in the AKW group and TPW group were given AKW and TPW, respectively, at weaning, and unexpectedly, the necrotic foci in the cardiac muscle were observed at the 15-week-old age in the AKW group, but not in the TPW group. The present study was designed to clarify the factors which are involved in that unusual increase of body weight and occurrence of cardiac necrosis. Eight dams in each group were given AKW or TPW (control) from day 0 of gestation to day 14 of lactation. The milk samples were collected on day 14 of lactation and analyzed for concentrations of calcium (Ca), sodium (Na), potassium (K), magnesium (Mg) and chloride (Cl). The AKW and TPW were also analyzed. Ca, Na and K levels in milk were significantly higher in the AKW group compared to the TPW group. No significant difference was noted in the Mg and Cl levels between the two groups. These data suggested that the Ca cation of AKW enriched the Ca concentration of the milk and accelerated the postnatal growth of the offspring of rats given AKW. PMID- 11201173 TI - Effect of troglitazone on the liver of a Gunn rat model of genetic enzyme polymorphism. AB - There is a possibility that serious liver dysfunction rarely observed in diabetic patients given troglitazone is attributable to idiosyncratic abnormalities in liver drug-metabolism. In addition, the results of blood biochemical examinations in serious cases of liver dysfunction showed a tendency for a high level of total bilirubin (T-Bil) over a long period compared with other indicators of liver dysfunction. Thus, we focused on genetic variation of UDP glucuronosyltransferases (UGTs) that are involved in the conjugation of troglitazone and bilirubin. In this study, Gunn rats, which are hereditarily deficient in the UGT1 family of UGT isozymes, and Wistar rats, the parent strain of Gunn rats, were treated with troglitazone for 3 months at dose levels of 0, 100 or 400 mg/kg to investigate two possibilities: first, whether the genetic deficiency in UGT1s induces an alteration of the metabolic profile of troglitazone followed by liver dysfunction, and second, whether the dosing of troglitazone to Gunn rats which show hyperbilirubinemia result in liver dysfunction. As a result, the metabolic profile of troglitazone in Gunn rats was much the same as that of Wistar rats, suggesting that genetic deficiencies in UGT1s did not influence the metabolic profile of troglitazone. Moreover, no elevation of blood biochemical parameters, such as asparate aminotransferase (AST) and alanine aminotransferase (ALT), or histopathological liver injuries, such as hepatocellular degeneration and necrosis, were observed in either strain of rats, and hyperbilirubinemia in Gunn rats was not aggravated by the dosing of troglitazone. These results strongly suggest that troglitazone was not metabolized by UGT1s but by other UGT isozyme (s) in rats, and that glucuronidation of troglitazone did not compete with glucuronidation of bilirubin in vivo. Thus, it is suggested that high levels of total bilirubin in patients with liver dysfunction induced by troglitazone are attributable to hypofunction due to hepatocellular injury, not to metabolic competition of bilirubin with troglitazone. Moreover, it is also suggested that the deficiency in the UGT1 family of UGT isozymes itself may not be the cause of liver dysfunction associated with troglitazone treatment. PMID- 11201174 TI - Characterization of UDP-glucuronosyltransferases (UGTS) involved in the metabolism of troglitazone in rats and humans. AB - UDP-glucuronosyltransferases (UGTs) involved in troglitazone glucuronidation in rats and humans have been characterized to support the previous toxicity study on troglitazone in Gunn rats and to examine whether the UGT polymorphism or inhibition of bilirubin metabolism is related to the clinically reported rare cases of liver failure. The experiments using Gunn rats revealed that UGT1 enzymes are not involved in troglitazone glucuronidation and that the responsible enzyme in rats was suggested to be UGT2B2, an androsterone UGT, by inhibition studies. In humans, contribution of UGT1A1 was estimated to be about 30% of the total troglitazone glucuronidation by UGTs, using human liver microsomes and recombinant UGTs. Other UGT1 and UGT2 enzymes seem to be responsible for the rest of the troglitazone glucuronidation in humans. The multiplicity of UGTs involved in troglitazone glucuronidation in humans may allow even patients lacking bilirubin UGT (UGT1A1) activity to produce troglitazone glucuronide. These observations suggest that the polymorphism of UGT is not the reason behind the liver failure induced by the troglitazone treatment, and troglitazone does not inhibit bilirubin glucuronidation in clinical treatment. In addition, the increased bilirubin level in the blood of patients who have troglitazone-induced liver failure is a consequence of liver injury and not due to inhibition of bilirubin glucuronidation by troglitazone. PMID- 11201175 TI - Comparison of sperm motility test methods (except computer-assisted sperm analysis) in rats under the condition of alfa-chlorohydrin treatment- collaborative investigation. AB - A comparison among rat sperm motility test methods including percent of motile sperm (% Motile), scoring method (Scoring), Ishii's method, Progressive Motility Test (PMT) and Sperm Quality Analyzer (SQA), was conducted using data gathered from eleven laboratories. As a unified study design, mature male rats were orally treated daily for approximately 1 week with alpha-chlorohydrin (ACH), which is known to affect the sperm motility at the epididymis, at dose levels of 2.5, 5 and 10 mg/kg, and then subjected to more than two test methods for sperm motility in each laboratory. Scoring (4 or 5 grades), Ishii's method, PMT and SQA showed high sensitivity for the detection of the effects of ACH, which were not considered to be inferior to a computer-assisted sperm analyzer (CASA). Longer incubation time before testing was considered to contribute to detecting the effects of ACH. In particular, we realized that Scoring was a favorable method even if the demerit of poor objectivity was allowed for. Percent Motile showed lower sensitivity than other test methods. The differences in sensitivity between % Motile and other methods were considered to be based on whether the defects of progressive motion could be detected. Although % Motile cannot clearly judge whether immotile sperm are dead or alive, the value is a great help for the interpretation of the result from other methods. Based on the characters for detectability, objectivity and efficiency, the most suitable method of sperm motility should be selected according to the purpose of the toxicity study. PMID- 11201176 TI - [A case of an advanced aged Eisenmenger's syndrome]. AB - We report a 70-year-old women with Eisenmenger's syndrome. Eisenmenger's syndrome with ventricular septal defect was diagnosed at another hospital when she was 32 years old. Then, she was referred to our hospital at age 60 old and she now is according to the out patient in over clinic. She have mild cardiac function, NYHA classification, was II-M, polycythemia cell blood count 535 x 10(4) and 17.2 g/dl in hemoglobin. Echocardiography suggested serious Eisenmenger's syndrome. The left ventricle was compressed, the blood pressure of the right ventricle exceeded 105 mmHg, and the onset of the right to left shunt flow was thought to be 250 msec bored on the electrocardiogram Q wave. The reason why the progression of complicated obstructive pulmonary artery disease was slow may have been become of the mildness of her polycythemia, and this is presumed to be the reason for her long survival to age 70. PMID- 11201177 TI - [Difference between first appraisal and clinical estimation appraisal in a new social insurance system covering long-term care service--in terms of outpatients and inpatients]. PMID- 11201178 TI - [Significance of abdominal ultrasonography on noticing aortic aneurysm--from study on diagnostic chance of aneurysm]. PMID- 11201179 TI - [Evaluation and improvement of medical and nursing service and caregiving for the elderly using MDS. 2. Diagnosis and symptoms, especially diseases causing care requiring conditions]. AB - Diagnoses recorded in the chapter E of Minimum Data Set (MDS) were analyzed in patients requiring care admitted in a geriatric hospital in Sapporo, Japan. They were classified as: A-diseases causing care-requiring conditions, B-their symptoms, and C-coexisting diseases requiring no care. Orthopedic diseases were not analyzed because they were not adequately recorded in MDS system. Class A diagnoses varied, but only five diagnoses were responsible for 3% or more of the total patients who required care. They were 1) Alzheimer's disease (AD), 2) Parkinson's disease, 3) dementia other than AD without neurological symptoms, 4) dementia other than AD with sequelae of stroke, and 5) sequelae of stroke without dementia. These diagnoses pooled represented over 90% of all patients. "Diagnoses and symptoms" in MDS were useful to 1) describe medical problems briefly in a predetermined format, 2) evaluate urgent or unstable conditions separately from stable diagnoses and symptoms, and 3) use common information by various professions, but have difficulties because 1) preselected diagnoses were few and unsuited to practices in Japan, 2) it is impossible to record a previous disease in the past that initiated the process leading to the present disabilities, and 3) it is also impossible to record the severities of the diseases and symptoms. PMID- 11201181 TI - [Current and coming new era of medical informatics in the aging society]. PMID- 11201180 TI - [Association between dementia and dietary nutrients]. PMID- 11201182 TI - [Neurological complication with cancer]. PMID- 11201183 TI - [Characteristics and the treatment of hypertension in the elderly]. PMID- 11201184 TI - [Exogenous lactate sustains synaptic activity and neuronal viability, but fails to induce long-term potentiation (LTP)]. AB - In Alzheimer's disease, brain glucose metabolic ratio decreases, whereas the brain lactate metabolic ratio increases. To investigate possible synaptic dysfunction in Alzheimer's disease, we examined the effects of exogenous glucose deprivation and replacement of glucose with lactate on the synaptic transmission, synaptic plasticity, and the morphological integrity of hippocampal neurons. Synaptic activity was estimated by the amplitude of the population spike (PS) recorded in the granular cell layer in the hippocampal slices from guinea pig and rat. Exogenous glucose deprivation caused the immediate depression of PS. Replacement of glucose with lactate induced transient decrease of PS, followed by spontaneous recovery of synaptic transmission. Neural activity recovered from transient glucose deprivation became resistant to the replacement of glucose with exogenous lactate. Glucose-supported synaptic transmission exhibited approximately 140% enhancement of PS (LTP). However, lactate-supported synaptic activity yielded approximately 110% potentiation of PS. Effects of exogenous glucose and lactate on the cell viability were examined by the propidum iodide uptake and LDH release in the organotypic hippocampal slice cultures. Hippocampal slice cultures incubated in medium containing 10 mM lactate suppressed the cell death during 48 h observation as well as those in the 10-30 mM glucose containing medium. These results indicate that lactate can sustain the neural transmission and support the morphological integrity of hippocampal neurons, but failed to induce LTP, which could at least in part, cause the memory impairment in Alzheimer's disease. PMID- 11201186 TI - [Analysis of dietary factors in Alzheimer's disease: clinical use of nutritional intervention for prevention and treatment of dementia]. AB - To determine dietary factors involved in the pathological process of Alzheimer's disease (AD), we analyzed food consumption and intake of nutrients using Self administered Diet History Questionnaire (DHQ) developed for Japanese. Sixty four AD patients and 80 age-matched healthy subjects were enrolled in this study. AD was diagnosed according to the criteria of DSM-IV. Dietary behaviors of AD patients was markedly deviated from those of age-matched healthy elderly. AD patients disliked fish and green-yellow vegetables and took more meats than controls. Energy-adjusted analysis of nutrients revealed that AD patients took less vitamin C and carotene. Most conspicuously, AD patients took significantly smaller amount of n-3 polyunsaturated fatty acid (PUFA) reflecting low consumption of fish, and their n-6/n-3 ratio was significantly increased. These habits started from 3 months to 44 years before the onset of dementia, suggesting these dietary abnormalities are not merely the consequence of dementia. Rather, it implies that AD might be a life style-related disease such as coronary heart disease, western style diet-associated cancer and hyperallergy. To see if cognitive function was improved by correcting the n-6/n-3 ratio, we prescribed eicossapentaenoic acid (EPA), one type of n-3 PUFA, for AD patients. Cognitive function was evaluated using MMSE. Administration of EPA (900 mg/day) improved MMSE significantly with maximal effects at 3 months and the effects lasted 6 months. However, the score of MMSE decreased after 6 months. The present study showed that nutritional intervention is useful for the prevention of AD, and also for the therapy of dementia, though it has some limitation. PMID- 11201185 TI - [The changes of peripheral-central nervous system interaction in Alzheimer's disease]. AB - Several lines of evidence suggest that the cholinergic system in the hippocampus plays a pivotal roll in regulating the peripheral metabolism of glucose and catecholamines. The injection of cholinergic stimulators including neostigmine, the acetylcholine esterase inhibitor, into the third ventricle or the hippocampus induces the elevation of glucose or catecholamines in plasma in rats. Under stress conditions, release of acetylcholine in the hippocampus increases, which coincides with the elevation of plasma glucose and catecholamines. Age-related reduction in responsivity of the cholinergic system in the hippocampus has been well-documented. The intrahippocampal neostigmine injection induces significantly attenuated responses in plasma glucose and catecholamines in rats, which finding suggested that changes in cholinergic system activity in the hippocampus could result in alteration of the peripheral metabolism of glucose and catecholamines. In Alzheimer's disease, the most common type of dementia, degeneration of the hippocampal cholinergic system is one of the most robust pathological features. Measurement of plasma catecholamines during a fasting state in groups of Alzheimer's disease subjects, vascular dementia subjects, and non-demented control subjects showed significantly lower plasma epinephrine levels in the Alzheimer's disease subjects. PMID- 11201187 TI - [Prediction of progression in patients with mild cognitive impairment using IMP SPECT]. AB - To examine the difference in functional brain imaging between mild cognitive impairment (MCI) and normal aging, we measured rCBF on functional brain imaging using 123I-IMP single photon emission computed tomography (IMP-SPECT) in 19 MCI patients who progressed to develop AD on follow-up and 23 probable Alzheimer's disease (AD) patients as well as 15 age-matched normal subjects. Baseline MMSE score was 25.3 (SD 1.2) in the MCI group and 17.5 (SD 3.3) in the AD group. The regions of interest (ROI) in the posterior cingulate gyrus, frontal, temporal and parietal cortices were drawn on the image of IMP-SPECT with reference to an individual MRI image. The rCBF ratio was calculated using ROI value in the cerebellum as a reference. Voxel-based analysis was also preformed using statistical parametric mapping (SPM). The rCBF ratio in the posterior cingulate gyrus was significantly reduced in the MCI group (mean 0.956, SD 0.080) and the AD group (mean 0.833, SD 0.118) compared to that in the normal group (mean 1.083, SD 0.084). In the frontal, temporal and parietal cortices, the rCBF ratio was significantly reduced only in the AD group compared to the normal group. At a fixed specificity of 80%, the diagnostic sensitivity in the discrimination between MCI patients and normal subjects was 80.5% when using rCBF ratio in posterior cingulate gyrus. In the SPM analysis, significant reduction of the rCBF in MCI group was observed only in the posterior cingulate gyrus, compared with normal subject group. Our results suggest that MCI patients presenting with a posterior cingulate hypoperfusion are at higher risk for transition from MCI to clinically recognizable AD. PMID- 11201188 TI - [Quantitative changes of elastin, fibrillin and collagen in abdominal aortic aneurysms]. AB - To examine quantitative changes of elastin, fibrillin and collagen in abdominal aortic aneurysms, including ruptured abdominal aortic aneurysms (RAAA), inflammatory abdominal aortic aneurysms (IAAA) and abdominal aortic aneurysms (AAA) were measured. Items measured included the desmosine content of the aorta (desmosine 1) or of the elastin fraction (desmosine 2), fibrillin content in the aorta, hydroxyproline in the aorta, collagen percent and elastin percent, and were compared with control samples from the nonaneurysmal aortic segments. The elastin contents (desmosine 2) in RAAA, IAAA and AAA were significantly lower than those of controls. The content of the desmosine 2 from IAAA and AAA did not show a negative association with Ca. The fibrillin contents of the aorta from RAAA, IAAA and AAA were significantly higher than those of controls. The collagen content in the RAAA aorta was significantly higher than that of controls. There was a correlation of the ratio of fibrillin to elastin components (fibrillin/desmosine 1 or fibrillin/desmosine 2 or fibrillin/elastin%) and the ratio of collagen to elastin components (collagen/desmosine 1 or collagen/desmosine 2 or collagen/elastin%). These results indicated that increasing fibrillin and collagen might be a complementary result of decreasing elastin crosslinks in the aorta. This phenomenon was markedly in RAAA. PMID- 11201189 TI - [Analyses of factors prolonging the length of hospital stay in elderly patients beginning hemodialysis]. AB - The aim of the present study is to clarify the factors causing prolongation of the length of hospital stay in elderly patients beginning hemodialysis. Patients aged over 60 years who had newly started hemodialysis (98 cases) were studied. These were 59 men and 39 women. The age was 73 +/- 7 years (mean +/- standard deviation). In each patient, the cause of renal failure (non-diabetes/diabetes), body mass index, comorbid conditions (cerebrovascular disease, ischemic heart disease, etc.), ambulation, cognitive function, urgency of the initiation of dialysis, occurrence of access failure, marital status, younger cohabitants, and the length of stay after initiation of dialysis were surveyed. The median and the mean of the length of stay were 37 and 49 days. Because of this disparity, a normal distribution of the length of stay could not be obtained. However, the distribution was transformed to close to normal by logarithmic conversion of the number of days. We used the log-converted value as the length of stay for statistical analyses. We investigated the influence of the differences of each factor on the length of stay. The subjects were divided into two groups for each factor. The mean and standard deviation of the length of stay was calculated respectively. Comparisons were carried out by unpaired t-test. Multiple regression analysis was also performed using background factors as explanatory variables, and the length of stay as a dependent variable. The factors presented by the nominal scale were converted to dummy variables. Eight variables in the unpaired t-test and seven variables in multiple regression analysis were statistically significant. All but one variable were common to both analyses. The gender was statistically significant only in the unpaired t-test. It could be explained by close correlation of gender with marital status. Access failure and urgent initiation of dialysis were dominant factors for the prolongation of the length of stay. Ischemic heart disease, diabetes, inability to walk, impaired cognitive function, and absence of a partner also prolonged the length of stay. PMID- 11201190 TI - [Comparison of complications in colonoscopic treatment in elderly and young subjects]. AB - PURPOSE: Owing to a recent increase in incidence of colonic adenoma and adenocarcinoma, colonoscopic treatments for elderly subjects are performed more frequently. We analyzed differences in complications between elderly and young subjects. OBJECT AND PROCEDURE: Subjects that had been treated with colonoscopy at Keio Cancer Center, were divided into two groups: one group (436) consisting of subjects below the age of 65, the other (176) consisting of subjects 65 and over. We analyzed differences in symptoms, complications and pathological findings. RESULT: No significant statistical differences were found in the occurrence of adenoma and adenocarcinoma between the young and the elderly group. COMPLICATIONS: Pain occurred in 9.4% of the young group and 10.2% of the elderly group, showing no significant difference between the two groups. Bleeding occurred in 0.7% of the young group and 3.8% of the elderly group and ulcerative scars were found in two of the latter. CONCLUSION: In the elderly the regenerative capacity of damaged blood vessels and tissues is greatly reduced, therefore bleeding and ulceration occurred more frequently. It was thus concluded that it is very important for elderly group to rest after endoscopical mucosal resection, polypectomy and biopsy in order to minimize the risk of bleeding in the digestive tract. PMID- 11201191 TI - [Comparison of complications in elderly and non-elderly patients with neurological diseases during admission to a rehabilitation hospital]. AB - Medical complications seen in admitted patients in a one-year period in a rehabilitation hospital were evaluated, and patients with neurological diseases were subdivided with age in order to determine trends of complications with occurred in the aged patients. Ninety-five of 117 patients (81.2%) suffered from complications, the most common were respiratory diseases, genitourinary diseases and psychoneurological diseases and events. Infectious diseases were very common throughout all ages. Significantly more cases and occasions of complications occurred in the aged patients (ages 65 or more, n = 59) than in the younger patients (aged under 65, n = 58), which suggests that complications tended to recur in the same patient in the aged group. Genitourinary diseases, especially urinary tract infection, was far more common in the aged group, predominating in women. Recurrences of stroke or poststroke epilepsy were more frequently seen in patients aged under 65. Traumas and fractures related to falls occurred more commonly in the aged group. Elderly patients were more susceptible to complications not directly related to the illness for which they were admitted. Complications occur quite commonly in aged patients admitted to our rehabilitation hospital, and careful attention should be paid to conditions unrelated to the illness causing admission, such as infectious diseases, especially for aged patients. PMID- 11201192 TI - [An autopsy case of dementia with Lewy bodies who showed the typical parkinsonism in the initial five years]. AB - A 76-year-old man with parkinsonism and dementia was reported. He developed resting tremor at age 69 followed by hypokinesia, rigidity and small step gait. L dopa ameliorated his symptoms with no hallucinations for the initial 5 years. His mental level did not decrease during that period. He was admitted to our hospital because of dehydration and fever at age 74. Subsequently, his cognitive function deteriorated, with visual hallucination. Serial brain CT studies displayed a progressive cerebral cortical atrophy without focal lesions. He died of respiratory distress syndrome and disseminated coagulopathy resulting from pneumonia, dehydration and syndrome malin. Postmortem examination revealed a marked bilateral loss of melanin-containing neurons with Lewy bodies in the substantia nigra and locus ceruleus. Lewy bodies were also in the basal nucleus of Meynert, with moderate neuronal cell loss. The distribution of Lewy bodies was widespread in the cerebral cortical areas, corresponding to the neocortical subtype according to the consensus guideline for the pathologic diagnosis of dementia with Lewy bodies. According to the criteria of the Consortium to Establish a Registry for Alzheimer's Disease, the age-related plaque score in the present case suggested Alzheimer's disease, although cortical neurofibrillary changes corresponded to stage II by the criteria of Braak and Braak. These pathological findings established the diagnosis of dementia with Lewy bodies from the quantitative and distributional viewpoints. Based on recent neuropathological evidence, a spectral theory, which presents idiopathic Alzheimer's disease and Parkinson's disease as the two extremes of a spectrum of neurodegeneration, has been proposed. Dementia with Lewy bodies is located in the middle of this spectrum. Pathological evaluation based on quantitative consensus guidelines is important to establish the diagnosis in patients with parkinsonism and dementia, since neuropathological changes of Alzheimer's disease, Parkinson's disease and dementia with Lewy bodies are often observed in a mixed manner in these patients. PMID- 11201193 TI - [Health promotion movements of the 21st century in Japan "Healthy Japan 21"--the role and responsibility of dental professionals]. PMID- 11201194 TI - [Alveolar ridge augmentation by tissue engineering]. PMID- 11201195 TI - [Influence of occlusal contacts on tooth displacement]. AB - During function, the tooth displacement path depends on occlusal contacts of the upper and lower teeth. Therefore, we must reconstruct occlusal relation carefully so as not to disturb physiological tooth displacement. In this investigation, tooth displacements were measured with the Displacement Transducer type M-3 in varying occlusal contact. The following conclusions were obtained. 1. The location of occlusal contacts influenced the tooth displacement of the upper first molar. Especially, an occlusal contact on the lingual inclination of the lingual cusp, buccal cusp had great influence. The tooth showed displacement toward the buccal direction, and it differed from the physiological tooth displacement path during clenching at the intercuspal position. 2. The location of occlusal contacts had little influence on the tooth displacement of the lower first molar. The tooth showed displacement toward the lingual direction. It was similar to the physiological tooth displacement. 3. On the upper first molar, the location of occlusal force influenced the Stress-Strain curve. Especially, the occlusal force on the buccal cusp had great influence on the amount of tooth displacement. 4. On the lower first molar, the location of occlusal force influenced the Stress-Strain curve. Especially, the occlusal force on the lingual cusp brought much displacement and a 2-phase displacement path, at times. Therefore, occlusal contacts have close relation to tooth displacement, and any occlusal reconstruction should harmonize with tooth displacement representing periodontal tissue distortion. PMID- 11201196 TI - [Reproduction of interocclusal relationship on stone casts]. AB - We fabricate a prosthesis by the indirect method. To fabricate a prosthesis functionally harmonized with the stomatognathic system, the interocclusal relationship must be reproduced on stone casts as accurately as possible. In this study, two subjects (one male, age 28; one female, age 31) were selected, and the occlusal contacts of complete arch stone casts made by three different impression methods were observed and compared with the true occlusal contacts in the intercuspal position in the mouth. To take the interocclusal records, we used a silicone bite checker. The following results were obtained. The occlusal contact points reproduced on the stone casts made by a conventional custom tray and a stock tray were rather low; that is, the number of occlusal contact points was less, and the size of the occlusal contact area was smaller, than in vivo. The states of the occlusal contact on the casts made by the same method differed from each other. On the bite-impression technique, the reproduction of occlusal contact was superior to that of the others. The shape, area, and number of contact regions under 60 micrometers were similar to contact regions under 30 micrometers in the mouth. There was no significant difference in reproduction between the custom tray and the stock tray. It is likely that the results were due to the distortion of the jaws and periodontal tissue during clenching at the intercuspal position, which could not be reproduced on the stone casts made by both the conventional custom and stock trays. PMID- 11201197 TI - [Questionnaire on "having a family dentist" and the status of oral health]. AB - In 1999, we gave a Questionnaire on "having a family dentist" to 414 workers (300 males, 114 females) at a government office. Oral health examination was also provided to the same subjects. The following results were obtained: 1. Female workers (43%) had a family dentist more often than male workers (29%), and the difference was significant (p < 0.01). 2. About 45% of the subjects received regular dental checkups at least once a year; however, half of them did not have a family dentist. 3. Convenience, comfort, and communication factors were the main reasons for choosing a particular dentist, while continuity, comprehensiveness, and specialty factors were not taken into consideration in choosing a dentist. 4. The persons who had family dentists had more FT and DMFT, and fewer total numbers of teeth than those without family dentists. From these results, it was suggested that people visited dentists with dental problems and received treatment repeatedly, and then they came to have family dentists. The habit of visiting a dentist regularly seeking checkups and prevention is not yet popular among Japanese adults. To improve oral health consciousness and to promote oral health, it should be recommended to receive regular checkups and oral health education by a family dentist. However, the present condition does not allow this system. Therefore in Japan, it should be encouraged to provide oral health examination and oral health education regularly at work sites, to improve the oral health of the adult population. PMID- 11201198 TI - Immunohistochemical demonstration of nerve terminals in the whole hard palate of rats by use of an antiserum against protein gene product 9.5 (PGP 9.5). AB - Sensory innervation of the entire hard palate was investigated in the rat using serial sections immunostained for protein gene product 9.5 (PGP 9.5), a neuronal marker. PGP 9.5-immunoreactive nerve endings were widely distributed in the hard palate, but the innervation pattern and density differed among portions. They were numerous at papillary protrusions including the incisal papilla, antemolar/intermolar rugae, and postrugal filiform papillae. Immunoreactive free nerve endings gathered at the summits of the connective tissue papillae, some of them entering deeply into the epithelium. Electron microscopy demonstrated that nerves in the postrugal filiform papillae reached the stratum corneum. The atrial region, possibly the most sensitive in the hard palate, showed unique innervation: its anterior part, adjacent to incisors, developed intraepithelial networks of fine and beaded nerves, whereas its posterior part revealed cone shaped nerve terminals formed on the connective tissue papillae of the atrial folds which comprised two lines of longitudinal flaps. Taste bud-like corpuscles gathered in the medial walls of the incisal canals and in the "Geschmacksstreifen" (taste stripes) present at the most anterior part of the soft palate. The hard palate of the rat is thus richly innervated, and is characterized by region-specific nerve endings which may be involved in mechano- and chemoreception in the oral cavity. PMID- 11201199 TI - The cytoarchitecture of the adult human parabrachial nucleus: a Nissl and Golgi study. AB - The parabrachial nucleus (PBN) plays important roles in numerous autonomic functions and in pain modulation. In different animal species, three main regions of the PBN have been identified: the m-PB, the l-PB, and the Kolliker-Fuse nucleus (KF). The KF has not been identified in humans. The present study used Nissl and Golgi-Cox material and morphoquantitative methods to investigate the cytoarchitectural organization of the adult human PBN, paying particular attention to neuronal features endowed with functional significance, i. e. the arborization of the neurons. The PBN neuron population is made up of elements which are heterogeneous in size, shape and dendritic arborization, and grouped into two regions, the lateral and medial PBN (l- and m-PB). It has been suggested that some large sized neurons located in the ventral region of the m-PB might be the counterpart of the KF. In the m-PB the fusiform neurons are the most numerous cells; in the l-PB the multipolar neurons prevail, and are particularly numerous in the dorsal l-PB. Since the dendritic arborization is generally the main target of afferent projections to a neuron, it is possible that the l-PB, and in particular its dorsal region, might be the main site for the endings of afferences to the human PBN. PMID- 11201200 TI - A corrosion casting/scanning electron microscope method that simultaneously demonstrates clear outlines of endothelial cells and three-dimensional vascular organization. AB - This paper describes a method that can definitively demonstrate endothelial cell boundaries on corrosion casts of arteries, veins, and capillaries. After perfusion with silver nitrate, a casting medium was injected into the entire vascular bed. The injected tissues were either exposed to light or immersed in the photographic developer to develop the silver halide, and corroded in a 5% NaOH solution at 60 degrees C overnight. Observations of the casts containing water in a low vacuum scanning electron microscope equipped with a cooling stage clearly showed endothelial cell boundaries on casts of every type of vessel as well as their three-dimensional architecture. The low vacuum scanning electron microscope images of wet casts were almost identical in quality to the back scattered electron images of dried casts without any coating. Secondary electron images of the dried casts with metal coating clearly showed endothelial cell outlines and nuclear imprints. The secondary electron images at high magnification indicated that silver granules were precipitated in the grooves along endothelial cell boundaries on the casts. Since this method can demonstrate endothelial cell boundaries of every type of vessel in addition to their three dimensional architecture, it will be a powerful tool for examining endothelial cell morphology and microvascular organization in pathological as well as normal tissues. PMID- 11201201 TI - The presence of a local immune system in the upper blind and lower part of the human nasolacrimal duct. AB - The nasolacrimal duct is exposed to exogenous agents, including potentially harmful microorganisms, coming from the eye surface by the lacrimal sac, and from the nasal cavity by the inferior meatus of the nose. The upper blind and lower part of the human nasolacrimal duct were examined immunohistochemically to ascertain the presence and localization of immunoglobulin-producing cells and the epithelial expression of IgA, IgM, and IgG in order to verify the possible antimicrobial properties of this duct. IgA-, IgM-, and IgG-positive immunocompetent cells were recognizable in the lamina propria of the upper blind and lower part of the human nasolacrimal duct, while an evident immunoreactivity for sIgA, IgM, and IgG was demonstrated in the cytoplasm of the apical epithelial cells. The results suggest that all the effector components of the mucosal immune system are present in that area of the human nasal mucosa next to the opening of the nasolacrimal duct as well as in the human lacrimal sac. PMID- 11201202 TI - Surface remodeling associated with vasopressin-induced membrane traffic in L6 myogenic cells. AB - The plasma membrane is dynamically remodeled as a function of the cell cycle, motility and membrane traffic. We have previously shown that arg8-vasopressin (AVP) stimulation of L6 myoblasts induces the activation of phosholipase D during the first minutes of stimulation, and the differentiation of 1,6 myoblasts as a long term effect. We now report that AVP also induces two types of morphological responses in L6 cells within a few minutes of stimulation: exocytosis, apparent as uncoated pits, and the generation of membrane projections and reffles. Thus, such an experimental model is suitable for the study of hormone-induced morphological surface modifications and their regulatory mechanisms. In L6 cells, AVP-induced projection generation depends on the integrity of microfilaments, intermediate filaments, and microtubules. Moreover, projection generation and exocytosis appear to be independently regulated phenomena: in fact, inhibition of the de novo synthesis of phosphatidylcholine inhibits membrane traffic but fails to block projection appearance. Conversely, the latter phenomenon, unlike exocytosis, is mediated by PI3-kinase signaling. Thus, AVP induces two early, independently regulated morphological modifications in L6 cells: exocytosis, involved in plasma membrane phospholipid turnover, and membrane projections, likely involved in cell migration. PMID- 11201203 TI - The ultrastructure of skeletal and smooth muscle in experimental protein malnutrition in rats fed a low protein diet. AB - Light microscopy of the pectoralis muscle of rats on a low protein diet did not show such morphological alterations as atrophy, degeneration, or sarcoplasmic edema, but electron microscopy occasionally demonstrated ultrastructural changes only in the sarcomeres of myofibrils. In the affected sarcomeres, the Z-line was disrupted and often showed a jagged structure. The Z-substance with electron opacity was frequently present flowing along the long axis of myofibrils, here referred to as the streaming of Z-lines. In addition, regular striations formed by the reciprocal arrangement of thick and thin filaments disappeared from the affected sarcomeres, though these filaments were still discernible. Two or more consecutive sarcomeres in a single myofibril were occasionally involved in these changes. A further two or more neighboring sarcomeres at the same level of myofibrils were affected transversely by these structural alterations. On the other hand, the ultrastructure of the intestinal smooth muscle was not affected by protein deficiency. The study suggests that the ultrastructural damage induced by a low protein diet is attributed to the activation of endogenous protease by the excess leaking of Ca2+ into the cytosol as a result of lipid peroxidation of cell membrane by raised free radicals, owing to the depletion of glutathione production by protein deficiency. It also suggests that the smooth muscle cells differ in their susceptibility to protein deficiency from the skeletal muscle cells. PMID- 11201204 TI - Enhanced visualization of weak colloidal iron signals with Bodian's protein silver for demonstration of perineuronal nets of proteoglycans in the central nervous system. AB - The present study aimed for a clear visualization of faintly deposited colloidal iron in tissue sections for light microscopy. Paraffin blocks containing paraformaldehyde-fixed brain tissue from healthy adult mice were cut into sections 10-15 microm thick. After deparaffinization, the sections were stained with fine cationic iron colloid at a pH value of 1.0-1.5, and treated with a mixture of potassium ferrocyanide and hydrochloride for Prussian blue reaction. Some sections were further treated with Bodian's protein silver after the Prussian blue reaction. This sensitized development of Prussian blue reaction with Bodian's protein silver more clearly visualized the faintly deposited cationic colloidal irons than the demonstration by Prussian blue reaction alone, and allowed an enhanced visualization of the perineuronal nets of sulfated proteoglycans in the brain. Thus, such fine perineuronal sulfated proteoglycans as those in the CA3 field of the hippocampus, which are weakly stained with cationic iron colloid and usually overlooked by a demonstration with only a Prussian blue reaction, could be clearly visualized with striking contrast by the sensitized development with Bodian's protein silver after the Prussian blue reaction. Preliminary hyaluronidase digestion erased Bodian's protein silver development of perineuronal sulfated proteoglycans. Though some axonal fibers were also additionally stained with Bodian's protein silver itself, this sensitized development is useful to enhance such weak colloidal iron signals as are hardly detectable by only Prussian blue reaction. PMID- 11201206 TI - Kupffer cell activation and hematopoiesis in the liver of autoimmune MRL-lpr/lpr mice. AB - Hematopoiesis can be induced in the adult murine liver by the administration of macrophage activators. The proliferation of macrophages and extrathymic T cells is spontaneously induced in the liver of autoimmune MRL-lpr/lpr mice, and deeply involved in the development of disease. To study the role of Kupffer cell activation in the induction of hematopoiesis and lymphocyte proliferation in the liver, we histologically analysed the kinetic and spatial relationship between Kupffer cells and hematopoietic cells or lymphocytes. At 5 weeks of age before the onset of disease, there were no appreciable histological changes in the liver. At 7 weeks, Kupffer cells had slightly increased in number, while hematopoietic islands were not yet detected. When disease had fully developed at 14 weeks, Kupffer cells were considerably increased in number and size, and exhibited numerous lysosomes. Hematopoietic cells of erythroid and myeloid series frequently appeared in the sinusoid, and lay in close apposition to Kupffer cells. Promyelocytes further migrated into the space of Disse to cluster there, being surrounded by the stellate cells (or fat-storing cells) and hepatocytes. After maturation, metamyelocytes and mature granulocytes were released into the sinusoidal circulation. Mitotic figures were detected in the cells of both erythroid and myeloid series. Lymphocytes proliferated in various sites such as in the sinusoid lumen, the space of Disse, and interlobular connective tissue, whether associated or not with Kupffer cells. The present results indicate that erythropoiesis, granulopoiesis, and lymphocyte proliferation are induced in the liver of MRL-lpr/lpr mice and are closely associated with Kupffer cell activation. PMID- 11201205 TI - Morphology of the glomerular nerve endings in the dorsal nasal ligament of the dog. AB - The nasal atrium appears to be an important sensory site in the dog, yet no literature is available concerning its nerve supply. The present paper demonstrates the occurrence of glomerular nerve endings in the canine nasal atrium, using immunohistochemistry for neurofilament protein (NFP) and for glial fibrillary acidic protein (GFAP). Glomerular nerve endings occurred on the perichondrium of the septal and the dorsal lateral nasal cartilages, and their terminal portions were attached with dense collagen fibril strands of the dorsal nasal ligament. The glomerular endings were derived from a thick parent axon which branched repeatedly. Complicated winding nerve fibers gave rise to numerous thin filamentous terminals. Accumulations of GFAP immunoreactive glial cells were also observed. Immunoelectron microscopy for NFP revealed several axon terminals in the glomerular endings which contained numerous neurofilaments and mitochondria and were incompletely covered by Schwann cell sheaths. The glomerular endings in the dog nasal vestibule are suggested to perceive tensional changes in the nasal dorsal ligament caused by the opening of the nostrils and to be involved in the reflex regulating the activity of the nasal muscles. PMID- 11201207 TI - Intensely negative-charged pericapillary spaces in the rat pineal gland. AB - Electron microscopy of ultrathin sections stained with cationic iron colloid revealed that the rat pineal gland is provided with wide and intensely negative charged pericapillary spaces. Light microscopically, the negative charging of the pericapillary spaces was completely eliminated by digestion with hyaluronidase and chondroitinase ABC. This pericapillary negative charging was also erased by digestion with collagenase. The results indicate that the negative charging is derived from sulfated proteoglycans which are bound to collagen molecules. These sulfated proteoglycans in the pericapillary spaces may retain numerous water molecules to form a tissue gel, and so act as a selective sieve regulating the passage of tissue molecules. PMID- 11201208 TI - Effects of short-term denervation and subsequent reinnervation on motor endplates and the soleus muscle in the rat. AB - The rat sciatic nerve was locally frozen, and changes in the nerve, motor endplates, and the soleus muscle were examined for up to 6 weeks by light and electron microscopy. The wet weights of denervated soleus muscles compared with contralateral values progressively declined to a minimum at 2 weeks after injury (60.7 +/- 2.5%) and began to reverse following 3 weeks. The sciatic nerve thoroughly degenerated after freezing. However, numerous regenerated myelinated and thin nerve fibers were observed at 3 weeks. They were considerably enlarged but still smaller than normal counterparts at 6 weeks postoperatively. Nerve terminals containing synaptic vesicles of endplates disappeared at day 1 and mostly reappeared at 3 weeks (about 70% of the endplates). All endplates examined were reinnervated at 4, 5, and 6 weeks. On the other hand, postsynaptic folds of muscle fibers seemed to be only slightly influenced by denervation or reinnervation. Ultrastructural alterations of myofibrils, in particular the loss of register, immediately appeared after denervation, spread progressively, peaked at 2 weeks, ameliorated following reinnervation, and became significantly normalized at 6 weeks after freezing. The proportion of type II fibers in the soleus muscle similary showed an increase and a decrease with a short delay in response to denervation and reinnervation, respectively. This study clearly demonstrated that the nerve supply affects the ultrastructural integrity of skeletal muscles. In addition, changes in the endplates and the soleus muscle evaluated in this study after short-term denervation are largely reversible following reinnervation. PMID- 11201209 TI - Rate and equilibrium constants for the epimerization of the endothelin receptor antagonist J-104,132 in aqueous solution. AB - The degradation of [5S-[5alpha,6beta,7alpha(R*)]]-2-butyl-5-(1,3-benzodioxol-5 yl)-7-[(2-carboxypropyl)-4-methoxyphenyl]-6-dihydro-5H-cyclopenta[b]pyridine-6 carboxylic acid (J-104,132) was studied in aqueous solution as a function of temperature and pH. The degradation reaction does not proceed to completion; rather, a stable equilibrium is attained in which approximately 2% of the degradate is produced. Kinetic data for the formation of the degradate are analyzed using an integrated form of the rate law for a reversible first-order reaction, and the forward and reverse rate constants and overall equilibrium constants are presented. Isolation and spectroscopic structural determination indicate that the degradate is the C7 beta-epimer of the drug. A mechanism for the epimerization reaction involving a novel enamine-like intermediate is proposed and shown to be consistent with the kinetic data. The rate and equilibrium constants are used to predict the room temperature stability of an injectable formulation of J-104,132, and these predictions are compared to actual data from long-term stability studies. It is concluded that the preformulation kinetic studies provide essential data needed for optimum drug product development. PMID- 11201210 TI - Structure-activity relationships for a collection of structurally diverse inhibitors of purine nucleoside phosphorylase. AB - Values of inhibition constants, Ki, and concentrations required for 50% inhibition, IC50, for a collection of structurally diverse competitive inhibitors of calf spleen purine nucleoside phosphorylase have been determined employing inosine as substrate. These values have been employed to create predictive quantitative structure-activity relationships (QSAR) which link structure to values of Ki and IC50. These QSAR models have substantial power to predict values and the associated uncertainties for Ki and IC50 for unknown, structurally diverse inhibitors of purine nucleoside phosphorylase. PMID- 11201212 TI - Two new aurones from marine brown alga Spatoglossum variabile. AB - Two new aurones, 4'-chloro-2-hydroxyaurone (1) and 4'-chloroaurone (2) were isolated from Spatoglossum variabile. The structures of these compounds were elucidated by modern spectroscopic techniques. PMID- 11201211 TI - Racemization kinetics of meluadrine tartrate in aqueous solution. AB - The kinetics of racemization of meluadrine tartrate in aqueous solution was investigated by HPLC, over the pH range of 1.2 to 12 at 40, 60 and 80 degrees C. The racemization was followed by measuring both the residual (R)-enantiomer and formed (S)-enantiomer of meluadrine. The pH-racemization rate profile of meluadrine showed a minimum racemization rate constant between pH 4 and 6, and the rate constant increased rapidly with decreasing pH below pH 3. In the basic region, the racemization rate constant showed a maximum at around pH 9. Four pathways of racemization of meluadrine are proposed, depending on the dissociation state of the phenolic and amino groups. The calculated racemization rate-pH profile agreed well with the observations. The values of activation energy (95-115 kJ/mol) suggest that a similar quinoid intermediate is involved throughout the pH range examined. The objective of this study is to clarify the racemization mechanism of benzylalcohol derivative with phenoric group. This study offers fundamental knowledge for the other benzylalcohol derivatives, which have similar moiety structure. PMID- 11201213 TI - Effects of structural modification of calcium spirulan, a sulfated polysaccharide from Spirulina platensis, on antiviral activity. AB - Calcium ion binding with the anionic part of a molecule was replaced with various metal cations and their inhibitory effects on the replication of herpes simplex virus type 1 were evaluated. Replacement of calcium ion with sodium and potassium ions maintained the antiviral activity while divalent and trivalent metal cations reduced the activity. Depolymerization of sodium spirulan with hydrogen peroxide decreased in antiviral activity as its molecular weight decreased. PMID- 11201214 TI - Hypnotic action of N3-substituted arabinofuranosyluracils on mice. AB - Methyl (2), ethyl (3), propyl (4), butyl (5), allyl (6), benzyl (7), o-, m-, p xylyl (8-10), and alpha-phenylethyl (11) derivatives of arabinofuranosyluracil (1) were synthesized and their pharmacological effects in mice were examined by using hypnotic activity and synergism with pentobarbital as indices for the CNS depressant effects. At a dose of 2.0 micromol/mouse by intracerebroventricular injection, the values of mean sleeping time induced by 7-11 were 144, 154, 117, 33, and 34 min, respectively, whereas the alkyl (2-6) derivatives did not cause any hypnotic activity. N3-o-Xylylarabinofuranosyluracil (8) displayed the most potent hypnotic activity among the derivatives tested. Certain derivatives (6-11) significantly prolonged the pentobarbital-induced sleeping time compared to control. The present study indicated that substitution with benzyl and/or related groups on the N3-position of arabinofuranosyluracil produced CNS depressant effects. PMID- 11201215 TI - Acid mediated hydrolysis of blueberry anthocyanins. AB - Acid mediated hydrolysis of anthocyanins was studied using capillary zone electrophoresis (CZE). A commercially available wild blueberry (Bilberry) extract was dissolved in different concentrations of TFA (0.1, 1, 3, 9%), then was subjected to thermodecomposition reaction at 95 degrees C. After the reaction, the samples were analyzed by CZE. The hydrolysis rate of each anthocyanin and the formation of the aglycon were determined by the change in the peak pattern of the anthocyanins in the electropherogram. Each anthocyanin peak decreased time dependently in a first order kinetic fashion. It was revealed that the hydrolysis rate of each anthocyanin was determined primarily by the type of conjugated sugar and not by the aglycon structure. The rate constant of anthocyanin hydrolysis was in the following order, arabinoside>galactoside>glucoside without regard to the aglycon structure. The kinetic behavior of this anthocyanin hydrolysis together with the CZE mobility allowed us to identify an unknown CZE peak as delphinidin 3 O-beta-arabinoside. At low TFA concentration, significant decomposition of the anthocyanidin nucleus occurred, but the glycoside hydrolysis predominated at high TFA concentration. It was further revealed that the aglycon released reacted successively to form polymeric products at higher TFA conditions. PMID- 11201216 TI - Hyaluronate depolymerization following thermal decomposition of oxytetracycline. AB - Depolymerization of sodium hyaluronate (HA) by tetracyclines was investigated. Reduction in HA molecular weight was followed by size exclusion chromatography with a low angle laser light scattering detector. On mixing with oxytetracycline hydrochloride (OTC) solution and incubating at 37 degrees C, HA was gradually depolymerized. OTC, a representative antibiotic, is known as a photosensitizer, and phototoxic side effects relevant to radicals have been reported. However, HA depolymerization required no irradiation. As time passed, OTC solution incubated at 37 degrees C got colored reddish brown, even in the dark. With reversed-phase HPLC separation, several peaks derived from decomposed OTC appeared. One of the peaks had an absorbance in the visible range. A quantitative correlation between the discoloration and the HA depolymerization rate was obtained. On the other hand, when samples were incubated below 25 degrees C, change of color was slight, and practically no HA depolymerization was observed after up to 4 h. Oxygen depletion by nitrogen saturation or addition of mannitol also prevented the depolymerization. Under anaerobic conditions, the color of the solution did not change, whereas it turned red under aerobic conditions in the presence of mannitol. The mannitol did not inhibit the OTC decomposition, but it preserved HA from damage. On the basis of the known decomposition of OTC and the results of HPLC separation, anhydrooxytetracycline can be proposed as the derivative causing HA depolymerization. PMID- 11201217 TI - O-ADP-Ribosylation in the NAD/NADase system: 2-alkanols as efficient substrates. AB - Several 2-alkanols (2-propanol, 2-butanol, 2-pentanol, etc.) were examined as substrates for ADP-ribosylation in the NAD/NADase enzymatic system. Even though these secondary alcohols have hydroxy groups that are subject to the steric influence of a methyl group, they were shown to be efficiently ADP-ribosylated. However, in the case of 3-alkanol (3-butanol), only slight ADP-ribosylation was observed. In this enzymatic reaction, 1,2-propanediol provided both 1-O- and 2-O ADP-ribosylation products in the ratio 1:1 as determined by 1H-NMR spectrometry. On the other hand, an equimolar mixture system of 1- and 2-propanols provided major 1-O- and minor 2-O-ribosylation products in the ratio 4:1. This is the first report of O-ADP-ribosylation of terminal secondary alcohols with the NAD/NADase enzymatic system. PMID- 11201218 TI - Hymenosides A-F, six new hemiterpene glucosides from the Japanese fern Hymenophyllum barbatum. AB - In the course of investigation of the bitter-tasting substances of the Japanese fern Hymenophyllum barbatum belonging to the family Hymenophyllaceae, six new hemiterpene glucosides called hymenosides A-F (1-6) have been isolated from the methanol extract, together with an acyclic bis-bibenzyl derivative, perrottetin H. This paper deals with the structure elucidation of the newly isolated glucosides. PMID- 11201219 TI - Synthesis of anacardic acids, 6-[8(Z),11(Z)-pentadecadienyl]salicylic acid and 6 [8(Z),11(Z),14-pentadecatrienyl]salicylic acid. AB - 11-Chloro-3-methoxy-2-undecenal was synthesized from 8-bromooctanol, and an annelation reaction with this aldehyde and ethyl acetoacetate proceeded to give the ethyl 6-(8-chlorooctyl)salicylate. Ethyl 6-(8-chlorooctyl)salicylate was converted to ethyl 6-(7-formylheptyl)-2-methoxybenzoate through the iodide after protection of the phenolic hydroxyl group. Finally, the Wittig reaction with the aldehyde and triphenylphosphonium iodides in the presence of BuLi gave the methoxybenzoates, and then treatments of these methoxybenzoates with BBr3 in CH2Cl2 and 10% NaOH in ethanol gave 6-18(Z),11(Z)-pentadecadienyllsalicylic acid (anacardic acid 3) and 6-[8(Z),11(Z),14-pentadecatrienyl]salicylic acid (anacardic acid 4) which were isolated from plants of the anacardiaceae. PMID- 11201220 TI - Brominations of steroidal hormone having alpha,beta-unsaturated ketone, 17-O acetyltestosterone, in the presence of silver triflate. AB - Bromination of 17-O-acetyltestosterone (17beta-acetoxyandrost-4-en-3-one) (1) was performed with 1, 5, and 10 eq of Br2 in AcOH-Et2O at room temperature. In all cases 2alpha,6beta- (2) and 2alpha,6beta-dibromo-17beta-acetoxyandrost-4-en-3-one (3) were obtained, although the yields were dependent upon the conditions used. Bromination of compound 1 with 10 eq of Br2 in the presence of silver trifluoromethanesulfonate (silver triflate, AgOTf) at room temperature for 12 h gave 2,7alpha-dibromo- (4) and 2,4,7alpha-tribromo-17beta-acetoxy-3-hydroxy-1 methylestra-1,3,5(10)-triene-6-one (5). The formations of the products were inferred on the basis of products obtained under controlled brominations of 1 in the presence of AgOTf, and of those obtained by the brominations of compounds 9 13 also in the presence of AgOTf. PMID- 11201221 TI - Synthesis and evaluation of novel 2-oxo-1,2-dihydro-3-quinolinecarboxamide derivatives as potent and selective serotonin 5-HT4 receptor agonists. AB - A series of 8'-substituted N-(endo-8-azabicyclo[3.2.1]oct-3-yl)-1-isopropyl-2-oxo 1,2-dihydro-3-quinolinecarboxamides were synthesized. The 5-HT4 receptor agonistic activity was evaluated using the isolated guinea pig ileum preparation. Of the compounds synthesized, N-(endo-8-(3-hydroxypropyl)-8-azabicyclo[3.2.1]oct 3-yl)-1-isopropyl-2-oxo-1,2-dihydro-3-quinolinecarboxamide (15a, TS-951) exhibited the most potent serotonin 5-HT4 receptor agonistic activity. This compound had a high affinity for the serotonin 5-HT4 receptor although it had no affinities for other broad spectrum receptors. Furthermore, it remarkably enhanced gastrointestinal motility in conscious fed dogs without unfavorable effects that non-selective serotonin 5-HT4 receptor agonist has. TS-951 may be useful in improving gastrointestinal dysfunction. PMID- 11201222 TI - Design and synthesis of N-terminal cyclic motilin partial peptides: a novel pure motilin antagonist. AB - Motilin antagonist was designed and synthesized on the basis of the structure activity relationship analysis of porcine motilin that we reported recently. The drug design was performed on a specific concept to reduce a flexibility of peptide conformation of porcine motilin partial peptide by its cyclization. The cyclic peptide was synthesized using Boc (tert-butyloxycarbonyl) solid phase methodology, followed by cyclization using the azide procedure, and tested for the binding activity to motilin receptor and smooth muscle contractile activity. The cyclic peptides 3, 4, and 5 showed antagonistic property on contraction assay (pA2 [the negative logarithm of molar concentration of antagonist causing a 2 hold shift to the right of the concentration-response curve for motilin]: 4.5, 4.34, and 4.04, respectively, in rabbit duodenum) and no contractile activity even at high concentration. PMID- 11201223 TI - Side chain-dependent binding of antitumor indoloquinoxaline derivatives to DNA: comparative spectroscopic and viscometric measurements. AB - NCA0424 (1) and its side chain positional isomer, NCA0465 (2), are indoloquinoxaline derivatives with potent antitumor activity. To investigate the effect of side chain position for binding with DNA, the interactions of 2 with various B-form DNAs were studied by spectroscopic (circular dichroism (CD), fluorescence and UV) and viscosity measurements and were compared with those of 1. The binding preference for the base sequence was different in each case. The CD spectra showed that 2 formed an asymmetric binding of indoloquinoxaline ring with adenine in DNA, whereas such a base selectivity was not found with 1. The binding features are discussed based on association constants and thermodynamic parameters, indicating the importance of the side chain position for binding specificity for DNA. PMID- 11201224 TI - Chiral recognition of thiaheterohelicenes by alkyl beta-D-pyranoside micelles. Influence of extension of helix. AB - Chiral recognition of alkyl beta-D-pyranoside micelles toward [7] and [5] heterohelicenes possessing helical structures was investigated by 1H-NMR and CD (circular dichroism) spectroscopy. In dodecyl maltopyranoside micellar solution, P and M enantiomers of tetrathia[7]heterohelicene (7TH), which have rigid and stable helixes, manifested different chemical shifts in their 1H-NMR spectra due to differences in the diastereomeric interactions, implying that the micelles undergo stronger recognition toward the M enantiomer than the P enantiomer. On the other hand, in octyl glucopyranoside micellar solution, trithia[5]heterohelicene (5TH) and two kinds of its derivatives which are rapidly equilibrated between the enantiomers in solution, gave no distinctly resolved 1H NMR peaks for either enantiomer even at a lowered temperature. However, these racemic [5]heterohelicenes in the micelles did develop induced CD absorptions owing to a displacement of the equilibrium, suggesting from the signs of their Cotton effects that the micelles prefer the M enantiomer to its antipode in conformity with the 1H-NMR results of 7TH. PMID- 11201225 TI - Solute-stationary phase interaction in gas liquid chromatography. Thermodynamic parameters for substituted halogenobenzene derivatives. AB - Thermodynamic parameters were determined by variable temperature experiments on the gas liquid chromatography (GLC) relative retention values, log gamma, of 3- and 4-substituted halogenobenzene derivatives under non-polar condition. These deltadeltaHdegrees(s)(R,X) had a compensational relation with the deltadeltaSdegrees(s)(R,X) values. The free energy change deltadeltaGdegrees(s)(R,X) which is estimated from the deltadeltaHdegrees(s)(R,X) and the deltadeltaSdegrees(s)(R,X) at 298 K is less than -23 kJ x mol(-1). The deltadeltaSdegrees(s)(R,X) values could be explained by translational entropy change for the adsorbed active complex between the solute and stationary phase. It is suggested that the interaction could be mainly expressed by the physical adsorption exclusive of hydrogen bonding. The deltadeltaGdegrees(s)(R,X) values for each halogen derivative have been the excellent linear lines taking the same slopes for the monosubstituted benzene derivatives, deltadeltaGdegrees(s)(R,X). The regression analyses of their intercepts were given using the descriptor evaluated as the molecular volume sigmaa(X) rather than sigmaM(X). The regression analysis for polyhalogenobenzene was also given successfully using sigmaa(Xn). PMID- 11201226 TI - Medicinal foodstuffs. XXI. Structures of new cucurbitane-type triterpene glycosides, goyaglycosides-a, -b, -c, -d, -e, -f, -g, and -h, and new oleanane type triterpene saponins, goyasaponins I, II, and III, from the fresh fruit of Japanese Momordica charantia L. AB - Eight cucurbitane-type triterpene glycosides called goyaglycosides-a, -b, -c, -d, -e, -f, -g, and -h and three oleanane-type triterpene saponins termed goyasaponins I, II, and III were isolated from the fresh fruit of Japanese Momordica charantia L. (Cucurbitaceae) together with five known cucurbitane-type triterpene glycosides momordicosides A, C, F1, I, and K. The structures of goyaglycosides and goyasaponins were elucidated on the basis of chemical and physicochemical evidence. PMID- 11201227 TI - Quantitative analysis of water dispersion conditions and pressure transmission characteristics of a wet kneaded mass. AB - In our previous paper [Watano S. et al., J. Powder Technology Japan, 37, 362-370 (2000)], a novel compaction tester was developed to quantitatively evaluate the water dispersion condition of a wet kneaded mass prepared by a paddle type kneader. It has been demonstrated that the physical properties of pellets prepared by extrusion granulation after the kneading can be well predicted by the pressure transmission obtained through the compaction tester. This paper describes a more detailed investigation of the water dispersion, its mechanism and pressure transmission characteristics of wet kneaded masses prepared under various operating conditions. First, kneading by a paddle type kneader was conducted to prepare wet masses under various binder contents using different additional methods and different starting materials. Secondly, water dispersion and pressure transmission characteristics of wet masses were investigated. After the wet kneading, the wet kneaded masses were extruded through a dome type extruder and were dried by a fluidized bed to prepare dry pellets. The relationship between water dispersion and pressure transmission can be expressed by a single line, regardless of binder content or methods of addition. This implies that these parameters have no effect on the water dispersion condition of the wet kneaded mass prepared by a high shear paddle type kneader. Different water dispersion characteristics and the mechanism obtained by different starting materials can also be evaluated by the pressure transmission data. Properties of dry pellets can also be predicted by the pressure transmission. It can be concluded that the developed compaction tester can quantitatively evaluate the water dispersion condition of a wet kneaded mass and also predict properties of the final extruded products. PMID- 11201228 TI - Bioactive constituents of chinese natural medicines. VI. Moutan cortex. (2): structures and radical scavenging effects of suffruticosides A, B, C, D, and E and galloyl-oxypaeoniflorin. AB - Five paeonol glycosides, suffruticosides A, B, C, D, and E, and a monoterpene glucoside, galloyl-oxypaeoniflorin, were isolated from the glycosidic fraction of Chinese Moutan Cortex, the root cortex of Paeonia suffruticosa Andrews, together with paeonolide, apiopaeonoside, galloyl-paeoniflorin, oxypaeoniflorin, and paeoniflorin. The structures of five suffruticosides and galloyl-oxypaeoniflorin were elucidated on the basis of chemical and physicochemical evidence. Suffruticosides A, B, C, and D, galloyl-oxypaeoniflorin, and galloyl-paeoniflorin exhibited more potent radical scavenging effects than alpha-tocopherol. PMID- 11201229 TI - Medicinal foodstuffs. XXII. Structures of oleanane-type triterpene oligoglycosides, pisumsaponins I and II, and kaurane-type diterpene oligoglycosides, pisumosides A and B, from green peas, the immature seeds of Pisum sativum L. AB - Two new oleanane-type triterpene oligoglycosides, pisumsaponins I and II, and two new kaurane-type diterpene oligoglycosides, pisumosides A and B, were isolated from the immature seeds (green peas) of Pisum sativum L. together with soyasaponin I, bersimoside I, dehydrosoyasaponin I, and their 6'-methyl esters. The structures of pisumsaponins and pisumosides were determined on the basis of chemical and physicochemical evidence as 22-O-malonylsoyasapogenol B 3-O-alpha-L rhamnopyranosyl(1-->2)-beta-D-galactopyranosyl(1-->2)-beta-D-glucopyranosiduronic acid (22-O-malonylsoyasaponin I), sandosapogenol 3-O-alpha-L-rhamnopyranosyl(1- >2)-beta-D-galactopyranosyl(1-->2)-beta-D-glucopyranosiduronic acid, 17-O-beta-D glucopyranosyl-6beta,7beta,13gamma,17-tetrahydroxy-19-kauranoic acid 19-O-beta-D glucopyranosyl(1-->2)-beta-D-glucopyranoside, and 6beta,7beta,13beta,17 tetrahydroxy-19-kauranoic acid 19-O-beta-D-glucopyranosyl(1-->2)-beta-D glucopyranoside, respectively. PMID- 11201230 TI - Analysis of the phase solubility diagram of a phenacetin/competitor/beta cyclodextrin ternary system, involving competitive inclusion complexation. AB - The competitive inclusion complexations in the ternary phenacetin/competitors/beta-cyclodextrin (beta-CyD) systems were investigated by the solubility method, where m-bromobenzoic acid (m-BBA) and o-toluic acid (o-TA) were used as competitors. The solubility changes of the drug and competitors as a function of beta-CyD concentration in the ternary systems were formulated using their stability constants and intrinsic solubilities. The decrease in solubility of phenacetin by the addition of competitors could be quantitatively simulated by the formulation, when both drug and competitor give A(L) type solubility diagrams. On the other hand, when one of the guests gives a B(S) type solubility diagram, its solubility change was clearly reflected in that of the another guest, i.e., phenacetin gave an A(L) type solubility diagram in the binary phenacetin/beta-CyD system and o-TA gave a B(S) type diagram in the binary o TA/beta-CyD system, but in the ternary phenacetin/o-TA/beta-CyD system, a new plateau region appeared in the original A(L) type diagram of phenacetin. This was explained by the solubilization theory of Higuchi and Connors. The solubility analysis of the ternary drug/competitor/CyD systems may be particularly useful for determination of the stability constant of a drug whose physicochemical and spectroscopic analyses are difficult, because they can be calculated by monitoring the solubility change of a competitor, without monitoring that of a drug. Furthermore, the present results suggest that attention should be paid to the type of the phase solubility diagram, as well as the magnitude of the stability constant and the solubility of the complex, for a rational formulation design of CyD complexes. PMID- 11201231 TI - Ten new labdane-type diterpenes from the fruit of Vitex rotundifolia. AB - Ten new labdane-type diterpenes were isolated from the fruit of Vitex rotundifolia L. (Verbenaceae), along with a known diterpene, vitexilactone. Their chemical structures were determined on the bases of spectroscopic data. PMID- 11201232 TI - The chemistry of indoles. CIII. Simple syntheses of serotonin, N-methylserotonin, bufotenine, 5-methoxy-N-methyltryptamine, bufobutanoic acid, N-(indol-3-yl)methyl 5-methoxy-N-methyltryptamine, and lespedamine based on 1-hydroxyindole chemistry. AB - Application of regioselective nucleophilic substitution reactions of 1 hydroxytryptamines to novel and simple syntheses of serotonin (1a), N methylserotonin (1b), bufotenine (1c), 5-methoxy-N-methyltryptamine (2a), bufobutanoic acid (3a), N-(indol-3-yl)methyl-5-methoxy-N-methyltryptamine (4), and lespedamine (5) are described. Effective syntheses of 5-benzyloxytryptamine and 1-methoxy-2-oxindoles are also reported. PMID- 11201233 TI - Reduction of acetals with samarium diiodide in acetonitrile in the presence of Lewis acids. AB - Transformation of acetals into ethers by partial reduction using a samarium diiodide-Lewis acids-acetonitrile system is described. The reaction with aromatic acetals occurred in good yields in the presence of aluminum chloride (2 eq) whereas the corresponding aliphatic, vinylic, and alkynyl derivatives did not afford ethers under the same conditions. Beta-elimination to give an enol ether becomes predominant when aliphatic acetals that possess a hydrogen at the 2 position are treated with iodotrimethylsilane in the presence of SmI2 or SmI3. PMID- 11201234 TI - Recent advances in gastrointestinal pathophysiology: role of heat shock proteins in mucosal defense and ulcer healing. AB - The defense mechanism of the gastrointestinal mucosa against aggressive factors, such as hydrochloric acid, bile acid and non-steroidal anti-inflammatory drugs, mainly consists of functional, humoral and neuronal factors. Mucus-alkaline secretion, mucosal microcirculation, and motility act as functional factors, while prostaglandins and nitric oxide act as humoral factors, and capsaicin sensitive sensory neurons act as neuronal factors. All the above factors are known to contribute to mucosal protection. In recent years, heat shock proteins (HSPs), to include HSP70, have been implicated to be an additional factor utilized for the defense mechanisms of the gastrointestinal mucosa at the intracellular level. The expression of HSP70 and HSP47 markedly changes during the development and healing of chronic gastric ulcers in rats. It was revealed that HSC70 (a constitutive form of HSP70) is coprecipitated with cyclooxygenase-1 and the neuronal form of nitric oxide synthase after treatment with a mild irritant (20% ethanol). A positive relationship between enhanced interaction of HSC70 with either cyclooxygenase-1 or nitric oxide synthase and mucosal protection against a strong irritant (100% ethanol) was observed. It was concluded that HSPs might contribute to mucosal defense mechanisms and ulcer healing, most probably through protecting key enzymes related to cytoprotection. PMID- 11201235 TI - Iron concentrations in human dermis assessed by microdialysis associated with atomic absorption spectrometry. AB - Until recently, the determination of metallic elements concentrations in normal skin, in vivo, was rare due to the lack of non-invasive techniques. Microdialysis has the advantage of being slightly invasive when applied to the collection in vivo of endogenous or exogenous substances from the skin. Iron is an active element in different cutaneous disorders. The aim of this work was to assess iron by atomic absorption spectrometry (AAS) after the collection of samples by microdialysis from human dermis. A first essential step, before determining the in vivo iron concentration in human dermis, was to establish an experimental protocol applicable to ex vivo as well as in vivo conditions. For this reason, this work deals only with the assessment of iron in ex vivo human dermis. A skin microdialysis technique and a calibration method, the No Net Flux, were used to quantify basal iron concentrations in human dermis and the same method was also used to determine in vitro and ex vivo iron recoveries. No differences were detected between in vitro and ex vivo recoveries. Ex vivo basal iron dermis concentrations ranged from 3.6 to 7.7 microg/l. This study shows that non invasive microdialysis is an efficient method for sampling iron from human skin. A sensitive and accurate AAS technique was able to assess low iron concentrations in human dermis. The strategy adopted for this work was efficient and appropriate for the determination of iron in human skin and experiments will be carried out in vivo. PMID- 11201236 TI - Rat small intestine muscle relaxation alkaloids from Orixa japonica leaves. AB - Two quinoline alkaloids, japonine (1) and eduline (2) were isolated from the methanol extract of the leaves of Orixa japonica as relaxants against rat small intestine muscle. The activity of these alkaloids was comparable to that of the typical muscle relaxant papaverine (4). This is also the first report of the isolation of eduline (2) from O. japonica. PMID- 11201237 TI - Inhibitory effects of ethaverine, a homologue of papaverine, on dopamine content in PC12 cells. AB - The inhibitory effects of ethaverine on dopamine content in PC12 cells were investigated. Ethaverine decreased dopamine content in a concentration-dependent manner in PC12 cells and showed 33.6% inhibition of dopamine content at a concentration of 1.0 microM for 24-48 h. The IC50 value of ethaverine was 1.4 microM. Dopamine content was lowered at 6h and reached a minimal level at 12h after exposure to ethaverine at 2.0 microM. The decreased dopamine level was maintained up to 48 h and then recovered to the control level at about 72 h. Tyrosine hydroxylase (TH) was inhibited at 6 h following treatment with ethaverine in PC12 cells and the activity was maintained at a reduced level up to 36 h (12-22% inhibition at 2.0 microM). These results indicate that ethaverine leads to a decrease in dopamine content by inhibition of TH activity. PMID- 11201238 TI - Prevention of the adverse effects of aprotinin in autologous fibrin glue. AB - To avoid the adverse effects of aprotinin (Apr) in autologous fibrin glue, we compared the inhibitory properties of four commercial anti-fibrinolytic agents (tranexamic acid (Tra), epsilon-aminocaproic acid (Ips), gabexate mesilate (Gab) and nafamostat mesilate (Naf)). The optimum conditions for the lysing of fibrin glue were an incubation temperature of 37 degrees C, and incubation medium containing urokinase at 100 U/ml and plasminogen at 100 mU/ml (for the washed glue), or neither (for unwashed glue). Fibrin glues without an anti-fibrinolytic agent were quickly lysed in the incubation medium, while those with an anti fibrinolytic agent were slowly lysed dose-dependently. Naf was the most potent inhibitor and had high affinity for the glue, but the other agents were poor inhibitors and had low affinity. The inhibition potency (IP) of each agent did not correlate with hydrophobicity, but a good correlation was obtained between the remaining coefficient (RC) and hydrophobicity. Naf did not affect the adhesive strength of the glue. These results indicate that Naf is the most suitable anti-fibrinolytic agent to replace Apr. PMID- 11201239 TI - Effects of substitution of conserved amino acid residues on the sugar-binding property of the tandem-repeat 32-kDa galectin of the nematode Caenorhabditis elegans. AB - The 32-kDa galectin (LEC-1) of the nematode Caenorhabditis elegans (C elegans) is composed of two tandemly repeated homologous sequences, each containing a carbohydrate-recognition domain (CRD). Using the polymerase chain reaction (PCR) with LEC-1 cDNA as a template and "megaprimers", we performed site-directed mutagenesis to substitute conserved amino acid residues in these domains. The resultant mutated LEC-1s were produced in E. coli, and their binding abilities were estimated by affinity chromatography. When one of the conserved amino acid residues in the first lectin domain was substituted, the binding ability of the mutant protein to asialofetuin-agarose was reduced but still remained. The binding ability of such mutants was similar to that of the recombinant half molecule containing the second lectin domain (Ch). However, when mutations were introduced into the second lectin domain, the binding ability of these mutant lectins to asialofetuin-agarose was significantly reduced just like the half recombinant molecule containing the first lectin domain (Nh). The different effects of the substitution of amino acid residues on the two lectin domains suggest that the binding properties of the two sites are different and that LEC-1 acts as a "heterobifunctional crosslinker." PMID- 11201240 TI - Enhanced adhesion of oxidized mouse polymorphonuclear leukocytes to macrophages by a cell-surface sugar-dependent mechanism. AB - Mouse thioglycollate-induced peritoneal macrophages effectively, in the absence of serum, recognized mouse polymorphonuclear leukocytes (PMNs) mildly oxidized with diamide, superoxide (hypoxanthine/xanthine oxidase) or t-butyhydroperoxide, or modified with N-ethylmaleimide (NEM). The recognition reached a maximum when PMNs were treated wtih each of the reagents at relatively low concentrations, and the recognition was decreased on treatment with reagents at higher concentrations. Glutathione depletion in the diamide-oxidized PMNs may cause enhanced adhesion to macrophages. Sialylated sugar chains attached to a peptide chain in glycophorin A and sialylated poly-N-acetyllactosaminyl sugar chains in lactoferrin and band 3 glycoprotein effectively inhibited the increased adhesion of the diamide-oxidized PMNs. Enzymatic removal of sialyl residues and the degradation of poly-N-acetyllactosaminyl sugar chains by pretreatment of PMNs with neuraminidase or endo-beta-galactosidase, respectively, lost their increasing ability for macrophage adhesion after oxidation with diamide, superoxide or t-butylhydroperoxide. Clustered sialylated poly-N acetyllactosaminyl sugar chains on the cell surface may be involved in the increased adhesion of the oxidized PMNs to macrophages. PMID- 11201241 TI - Comparative analysis of proteoglycans synthesized by chick corneal stromal cells in cell culture and organ culture. AB - Proteoglycans (PGs) synthesized by chick corneal stromal cells in cell culture and organ culture were metabolically radiolabelled with [35S]sulfate (for glycosaminoglycans) and [3H]leucine (for core proteins). Media, cell extracts and organ extracts from cultures were chromatographed on DEAE-Sephacel columns and separated into three fractions: the pass-through fraction (Fraction 1: nonsulfated PGs, hardly sulfated PGs, or glycoproteins with some oligosaccharides), the fraction eluted with a low salt concentration (Fraction 2: undersulfated PGs), and the fraction eluted with a high salt concentration (Fraction 3: highly sulfated PGs). The PG compositions of each fraction of cell culture and organ culture were then compared. While the proportions of highly sulfated KSPG in Fractions 3 of medium and cell extract of cell culture were both very low compared with those of medium and organ extract of organ culture, respectively, the proportions of highly sulfated CS/DS PG in Fractions 3 of those of cell culture were higher than those of organ culture. On the other hand, the proportions in the 35S activities of nonsulfated or undersulfated KSPG in Fractions 1 and 2 of medium and cell extract of cell culture were comparable to those of organ culture. Furthermore, the proportions of core proteins of undersulfated KSPG in Fractions 2 were higher in cell culture than in organ culture. These results show that, when the cells are cell-cultured, the degree of sulfation of KS chains decreases markedly, but the syntheses of the glycosaminoglycan backbone and core protein are maintained. PMID- 11201242 TI - Expressions of bradykinin B2-receptor, kallikrein and kininogen mRNAs in the heart are altered in pressure-overload cardiac hypertrophy in mice. AB - Angiotensin-converting enzyme inhibitors prevent cardiac hypertrophy in vivo, and a component of this ameliorative effect has been attributed to accumulation of kinins in cardiac tissues. However, little is known regarding the levels of kallikrein-kinin components in the heart during the development of cardiac hypertrophy. The objectives of the present study were to define the effects of pressure-overload cardiac hypertrophy on cardiac levels of kininogen, kallikrein and bradykinin B2 receptor mRNAs. The pressure-overload induced by aortic constriction produced cardiac hypertrophy in mice after 14 and 28d, assessed from the increased ratios of heart weight to body weight and elevation of brain natriuretic peptide mRNA in the heart. B2 receptor mRNA rapidly decreased in the heart within 7 d after the operation, subsequently returning to those of sham operated animals. In contrast, levels of both low-molecular-weight kininogen and tissue kallikrein mRNAs were increased 7, 14 and 28 d after aortic constriction. These findings suggest that the mechanical load or stretch in cardiac tissue by pressue-overload rapidly produces the downregulation of B2 receptor expression during the initial stage which may allow the promotion of cardiac hypertrophy induced by a mediation of hypertophic factors such as angiotensin II, while upregulation of kininogen and kallikrein mRNAs during the chronic stage may lead to an enhancement of local kinin generation in the heart, from which further progression of cardiac hypertrophy during later stages may be regulated. PMID- 11201243 TI - SP-40,40 is a component of plasminogen activator inhibitor-1-binding protein and stabilizes plasminogen activator inhibitor-1 activity. AB - A complex of plasminogen activator inhibitor-1 (PAI-1) and PAI-1-binding protein (PAI-1-BP) contained S-protein (vitronectin), PAI-1 and unidentified 40-kDa protein on SDS-PAGE under reducing conditions. By Western-blot analysis, the 40 kDa protein was identified as SP-40,40 using anti-SP-40,40 antibody. Therefore, it was thought that PAI-1-BP consisted of S-protein and SP-40,40. It is known that PAI-1 is a labile protein which becomes inactive during incubation at 37 degrees C. However, after the incubation of PAI-1 with SP-40,40 at 37 degrees C for 1 h, PAI-1 could still form a complex with tissue plasminogen activator (tPA), and it inhibited plasmin formation in the mixture of plasminogen and urine plasminogen activator (uPA). The results clearly indicated that SP-40,40 stabilized PAI-1 activity as well as S-protein did. PMID- 11201244 TI - Characterization of microsphere embolism-induced impairment of learning and memory function and the cholinergic system. AB - The impairments of learning and memory function and of the cholinergic system were examined in rats with microsphere embolism. Microsphere embolism was induced by injection of 900 microspheres with a diameter of 48 microm into the right internal carotid artery. The retention latency of a passive avoidance test was shortened and the escape latency of a water maze test was prolonged, when the animals were tested on the 5th to 10th day after the embolism, suggesting learning and memory dysfunction. Cholinergic parameters of the striatum and hippocampus, such as acetylcholine (ACh) content (67 and 60% decrease, respectively), choline acetyltransferase (ChAT) activity (45 and 56% decrease, respectively), and Bmax of muscarinic acetylcholine M1-receptor (43 and 37% decrease, respectively), were reduced on the 11th day after the embolism, suggesting attenuation of ACh synthesis and a decrease in the number of muscarinic acetylcholine M1-receptors mainly in the striatum and hippocampus. Areas not stained with triphenyltetrazolium chloride, an indication of infarction, were detected mainly in the striatum and hippocampus and partly in the frontal cortex on the 11th day after the embolism. The results suggest that an animal with microsphere embolism may be a good ischemic model with relatively sustained impairments of learning and memory function and of the striatal and hippocampal cholinergic system. PMID- 11201245 TI - Na+ and K+ dependence of L-glutamate-induced suppression of astrocyte stellation in culture. AB - We have recently found that L-glutamate suppresses astrocyte stellation induced by various stimuli, and that this effect of L-glutamate is mimicked by transportable glutamate uptake inhibitors. To test the possible role of the glutamate transporter in the regulation of astrocyte morphology, we investigated the Na+ and K+ dependence of this effect of L-glutamate. In astrocyte cultures obtained from the cerebral cortex of neonatal rats, the L-glutamate-induced suppression of astrocyte stellation was significantly attenuated in a low- Na+/high- K+ medium and by the Na+ -K+ pump inhibitor ouabain. These results support that astrocyte morphology is affected by the activity of the Na+ dependent glutamate transporter. PMID- 11201246 TI - Glycyrrhetinic acid induced apoptosis in murine splenocytes. AB - Glycyrrhetinic acid (GA) is known to inhibit glucocorticoid metabolism inhibiting 11beta-hydroxysteroid dehydrogenase (11beta-HSD). Moreover, GA administration to mice has been shown to affect the lymphoid organs through elevation of endogenous corticosterone concentration. The effect of GA administration on thymus has been demonstrated to show that considerable amounts of thymocytes undergo apoptosis by elevated levels of corticosterone in systemic circulation. However, the effect of GA administration on peripheral lymphocytes has remained unknown. In our current study, we demonstrated that a significant involution of spleen as well as thymus occurred within 24 h of a single administration of GA in mice. In addition, a flow cytometric analysis of the splenocytes taken from mice treated with GA showed a significant increase in the number of apoptotic cells which exhibited translocated phosphatidylserine outside the plasma membrane. Furthermore, considerable inhibition of 11beta-HSD activity in GA-treated mice was observed in liver and spleen, resulting in a significant increase in concentration of corticosterone in the blood. These facts showed that the apoptosis of splenocytes was the result of indirect effect of GA through elevated levels of corticosterone. We confirmed this using cultured splenocytes in vitro where no apoptotic effect of GA was observed. We concluded that GA administration induces cell death of not only thymocytes that are naive to corticosterone, but also splenocytes that are usually stable to its physiological concentrations. PMID- 11201247 TI - Hair analysis for pharmaceutical drugs. I. Effective extraction and determination of phenobarbital, phenytoin and their major metabolites in rat and human hair. AB - In order to establish an analytical method for the determination of phenobarbital (PB), phenytoin (PPH) and their hydroxylated metabolites in hair, animal model experiments were performed. Five male dark-agouti pigmented rats, aged 5 weeks, were intraperitoneally and orally administered PB or PPH independently at 25 mg/kg once a day for 5 successive days. The growing back hair was collected 15d after the first administration. Four typical extraction methods, using NH4OH methanol-acetone, TFA-methanol-acetone, 1M sodium hydroxide and proteinase K, were evaluated using the rat hair samples containing PB or PPH. Methanol-acetone NH4OH (10: 10: 1) was the best extraction method from all aspects, such as high extraction efficiency and low noise. The analytes in the extract were methylated in acetonitrile with 20% tetramethylammonium hydroxide and methyliodide at 70 degrees C for 10 min. After purification with Bond Elut Certify, the methylated products were analyzed by GC-MS. From rat hair, PB, p-hydroxy PB, PPH and p hydroxy PPH were detected at average concentrations of 26.9, trace, 4.2 and 0.4 ng/mg with an intraperitoneal (i.p.) injection, and at 30.9, trace, 4.0 and 0.4 ng/mg with oral administration, respectively. There was little difference in hair concentrations between i.p. injection and oral administration. This method was applied to the head hair of two patients who orally took toxic amounts of PB and two volunteers who orally took 100 mg of PPH daily for 5 d. The hair concentrations of PB in the two patients were 16.2 and 14.7 ng/mg, and those of PPH in the two volunteers were 3.3 and 0.1 ng/mg. PMID- 11201248 TI - Higher yielding isolation of kinsenoside in Anoectochilus and its antihyperliposis effect. AB - A higher concentration of kinsenoside, 3-(R)-3-beta-D-glucopyranosyloxybutanolide (1), was detected in the crude drug Anoectochilusformosanus, and A. koshunensis by HPLC analysis. A methylation reaction occurred to give methyl ester (4) when the lactone ring of 1 was cleaved by silica gel catalysis using methanol containing solvent used in the purification step resulting in difficulty to purify 1. To avoid the cleavage reaction, a reversed-phase or silica gel column without methanol was used to give a high yield of 1. In an anti-hyperliposis assay using high-fat diet rats, 1 significantly reduced the weights of body and liver, and also decreased the triglyceride level in the liver compared to those of control rats. On the other hand, the epimer of 1, 3-(S)-3-beta-glucopyranosy loxybutanolide (2), trivially named goodyeroside A, which was isolated from Goodyera species, had no effect for anti-hyperliposis. In aurothioglucose-induced obese mouse, 1 suppressed the body and liver weight increase, significantly ameliorated the triglyceride level in the liver, and also reduced the deposition of uterine fat-pads. PMID- 11201249 TI - Gaussian quadrature as a numerical integration method for estimating area under the curve. AB - This paper presents a numerical integration method for estimating the area under the curve (AUC) over the infinite time interval. This method is based on the Gauss-Laguerre quadrature and produces AUC estimates over the infinite time interval without extrapolation in a usual sense. By contrast, in traditional schemes, piecewise interpolation is used to obtain the area up to the final sampling point, and the remaining portion is extrapolated using nonlinear regression. In this case, there is no theoretical consistency between the quadrature and extrapolation. The inconsistency may cause certain problems. For example, the optimal sampling criterion for the former is not necessarily optimal for the latter. Such inconsistency does not arise in the method of this work. The sampling points are placed near the zeros of Laguerre polynomials so as to directly estimate the AUC over the infinite time interval. The sampling design requires no particular prior information. This is also advantageous over the previous strategy, which worked by minimizing the variance of estimated AUC under the assumptions of particular pharmacokinetic and variance functions. The original Gaussian quadrature is believed to be inappropriate for numerical integration of data because of several restrictions. In this paper, it is shown that, using a simple strategy for managing errors due to these restrictions, the method produces an estimate of AUC with practically sufficient precision. The efficacy of this method is finally shown by numerical simulations in which the bias and variance of its estimate were compared with those of the previous methods such as the trapezoidal, log-trapezoidal, Lagrange, and parabolas-through the-origin methods. PMID- 11201250 TI - A protective effect against undesirable increase of dihydroetorphine permeation through damaged skin by using pressure-sensitive adhesive tape with an ethylene vinyl acetate co-polymer membrane. AB - The release kinetics of dihydroetorphine (DHE) from pressure-sensitive adhesive (PSA) tape with an ethylene-vinyl acetate co-polymer (EVA) membrane as a diffusion-controlling membrane and its protective effect from an unpredictable increase in skin permeation of DHE caused by stratum corneum damage were investigated. The DHE flux through the EVA membrane was enhanced with the increase of vinyl acetate content. Although the DHE release from the PSA tape was proportional to the square root of the time, the release from the PSA tape covered with the EVA membrane was dominated by zero-order rate. The release rate increased by the addition of isopropyl myristate to the PSA layer, due to the increase of solubility and diffusivity of DHE in the PSA layer, and not a decrease of permeation resistance in the EVA membrane. When using the PSA tape with the EVA membrane, the steady-state flux of DHE through hairless rat skin with stratum corneum damage was not 2-fold more than that through non-damaged skin. Plasma DHE concentration rose promptly above 5 ng/ml after the application of the PSA tape onto the damaged skin in hairless rat. In contrast, when the PSA tape with the EVA membrane was applied onto the damaged or non-damaged skin, plasma concentrations in the both cases were maintained in the therapeutic range (0.2-1.2 ng/ml). These results suggest that the PSA tape with the EVA membrane can be used to protect from the unpredictable increase in skin permeation of DHE due to stratum corneum damage. PMID- 11201251 TI - Complete sequences and expression kinetics of racG, racH, racI and racJ genes in Dictyostelium discoideum. AB - We sequenced and characterized the expression patterns of the genes (racG, racH, racI and racJ) in the Rho-family. The nucleotide sequences of these genes suggest that racI would be a pseudogene, while the other genes are likely to encode typical Rac proteins which contain either GTP-binding domain or CAAX prenylation motif as observed in other members of the family. The Northern blot analyses show that the expression patterns of these genes are distinctively regulated during development. The racG gene is expressed at almost the same level from the vegetative to the slug stage, but the amount of its transcript gradually decreases after culmination. Expression of the racJ gene is undetectable at the vegetative stage, becomes observable at the mound stage, reaches a peak at the slug stage and then suddenly disappears in the culmination stage. The racH gene is expressed in two forms of transcripts, both of which are undetectable at the vegetatively growing stage but abruptly increase in amount after starvation. Southern blot hybridization analysis demonstrates that these transcripts were derived from a single copy of the gene. Such distinct kinetics of the expression patterns suggests that these genes would have unique roles in Dictyostelium development. PMID- 11201252 TI - Exercise improved accumulation of visceral fat and simultaneously impaired endothelium-dependent relaxation in old rats. AB - Exercise decreases plasma total cholesterol and triglycerides, and simultaneously, increases high density lipoprotein (HDL) cholesterol. Furthermore, it has been reported that exercise improves insulin resistance. As a result, exercise is believed to aid in preventing atherosclerosis. However, we do not know whether exercise protects against the development of atherosclerosis in the elderly. The aim of this study was to ascertain whether exercise prevented atherosclerosis in aorta of old rats. Exercise for three months did not affect plasma lipid levels but decreased accumulation of visceral fat and body weight without the reduction of food intake in two year old rats. Exercise also decreased triglycerides in liver and gastrocnemius white muscle. Exercise resulted in an elevation of plasma lipid peroxide (LPO) levels without affecting superoxide dismutase (SOD). Exercise impaired the endothelium-dependent relaxation of the thoracic aorta caused by acetylcholine in old rats. In summary, the results of our study indicate that exercise induces the reduction of visceral fat, body weight and triglyceride contents in tissues in old rats. These results seems to show that exercise improves insulin resistance. However, exercise simultaneously may cause impaired endothelium-dependent relaxation by elevation of LPO in old rats. PMID- 11201253 TI - Effects of peppermint (Mentha piperita L.) extracts on experimental allergic rhinitis in rats. AB - The present study was carried out to clarify the effects of extracts of the leaves of Mentha piperita L. on experimental allergic rhinitis. The 50% EtOH extract of peppermint inhibited histamine release from rat peritoneal mast cells induced by compound 48/80. The effect was dose-dependent and significant inhibition was observed at a concentration of 3 microg/ml. In addition, the 50% EtOH eluate separated from the 50% EtOH extract of peppermint by column chromatography (DIAION HP-20) was also effective in inhibiting histamine release at a concentration of 1 microg/ml. Nasal symptoms, sneezing and nasal rubbing induced by antigen challenge in actively sensitized rats were inhibited by oral administration of the 50% EtOH eluate. Significant inhibition of sneezing and nasal rubbing was observed at doses of 300 and 1000 mg/kg, p.o., respectively. Furthermore, the 50% EtOH eluate inhibited dye leakage into the nasal cavity of rats induced by antigen in a dose-dependent manner. These results suggested that extracts of Mentha piperita L. may be clinically effective in alleviating the nasal symptoms of allergic rhinitis. PMID- 11201254 TI - Does post-translational modification influence chaperone-like activity of alpha crystallin? I. Study on phosphorylation. AB - It is difficult to isolate derivatives of alpha-crystallin with only one type of post-translational modification, because this protein is subjected to several different types of modification. In the present study using bovine lens proteins, we isolated mono-phosphorylated alphaB-crystallin with no other post translational modifications. Using this material, we demonstrated that mono phosphorylation reduced the activity of alphaB-crystallin by approximately 30%. Our results confirmed that investigation of the correlation between chaperone like activities of alpha-crystallin and post-translational modification is important to understand the mechanism of cataract formation. PMID- 11201255 TI - Autotransporter proteins, evolution and redefining protein secretion: response. PMID- 11201256 TI - Autotransporter proteins, evolution and redefining protein secretion: response. PMID- 11201257 TI - Mapping of a chromosome replication origin in an archaeon: response. PMID- 11201258 TI - Gonococcal lipooligosaccharide: an adhesin for bacterial dissemination? Response. PMID- 11201259 TI - The pathology of Chlamydia pneumoniae lesions in humans and animal models. PMID- 11201260 TI - Dual role for cytochrome cbb3 oxidase in clinically relevant proteobacteria? PMID- 11201261 TI - Lipid-CD1-reactive T cells. PMID- 11201262 TI - Uneasy bedfellows: science and politics in the refutation of Koch's bacterial theory of cholera. PMID- 11201263 TI - Nineteenth-century medical landscapes: John H. Rauch, Frederick Law Olmsted, and the search for salubrity. PMID- 11201264 TI - The white plague goes to college: tuberculosis prevention programs in colleges and universities, 1920-1960. PMID- 11201265 TI - Beyond the "Two Psychiatries": Jack Pressman's Last Resort and the history of twentieth-century American psychiatry. Introduction. PMID- 11201266 TI - Jack Pressman and the future of the history of psychiatry. PMID- 11201267 TI - Toward new narratives of twentieth-century medicine. PMID- 11201269 TI - Fifty years of the British National Health Service: mixed messages, diverse interpretations. PMID- 11201268 TI - Therapeutics and the history of psychiatry. PMID- 11201270 TI - The parent trap. PMID- 11201271 TI - Stop stressing me. PMID- 11201272 TI - The skin-cancer scare. The lesion on Bill Clinton's back was easily cured, but it offers a stark reminder of the sun's hazards. PMID- 11201273 TI - Searching for the God within. PMID- 11201274 TI - Three-dimensional arrangement of muscle bundles in the outer layers of rodentia vasa deferentia. AB - Three-dimensional arrangement of the smooth muscle bundles of the outer layer of the vas deferens musculature in mammals (guinea-pigs, rats and mice) was examined under the scanning electron microscope (SEM) after removal of fibrous connective tissue elements. Muscle fibers of all examined animals formed bundles. In the guinea-pig, similar sized bundles extended longitudinally along the tubular vas deferens and branched to anastomose with branches of neighboring bundles to create a net which was regular in form. In the rat, longitudinal muscle bundles constituted an outer layer in the form of a net, which was roughly enmeshed with variously-sized, transverse or oblique bundles in anastomosis with underlying longitudinal bundles. In the mouse, longitudinal bundles of irregular thickness branched into many small bundles and anastomosed not only with neighboring bundles to create an irregular net. In both the rat and the mouse there were bundles extending over many other bundles to anastomose with them at a far point. Junctional structures were well developed between neighboring fibers. Myofibrils were represented as thin streaks on muscle fiber surfaces. Varicosed nerve fibers existed between muscle fibers and in narrow cytoplasmic grooves in all the examined animal species. The findings are discussed in correlation with electrophysiological data. PMID- 11201275 TI - The brain of the Nemertodermatida (Platyhelminthes) as revealed by anti-5HT and anti-FMRFamide immunostainings. AB - The taxa Nemertodermatida and Acoela have traditionally been considered closely related and classified as sister groups within the Acoelomorpha Ehlers 1984 (Platyhelminthes). Recent molecular investigations have questioned their respective position. In this study, the 5-HT and FMRFamide immunoreactivity (IR) in the nervous system of two nemertodermatids, Nemertoderma westbladi and Meara stichopi, is described. The 5-HT immunoreactive pattern differs in the two nemertodermatids studied. In M. stichopi, two loose longitudinal bundles of 5-HT immunoreactive fibres and an basi-epidermal nerve net were observed. In N. westbladi the 5-HT-IR shows a ring-shaped commissural structure, different from the commissural brain of acoels. In both nemertodermatids, FMRFamide immunoreactive nerve fibres followed the 5-HT-immunoreactive fibres. It is demonstrated that the Nemertodermatida have neither a 'commissural brain' structure similar to that of the Acoela, nor a 'true', ganglionic brain and orthogon, typical for other Platyhelminthes. The question of the plesiomorphic or apomorphic nature of the nervous system in Nemertodermatida cannot yet be answered. The neuroanatomy of the studied worms provides no synapomorphy supporting the taxon Acoelomorpha. PMID- 11201276 TI - Structural and biochemical analysis of the parasite Gordius villoti (Nematomorpha, Gordiacea) cuticle. AB - The cuticle of the nematomorpha Gordius villoti is a proteinaceous extracellular structure that covers the body during the endoparasitic life in the hemocoelic cavity of insect hosts, and of the free-living adult animals. The ultrastructure of the cuticle has a complex spatial organization with several parallel layers of large diameter fibers, interposed thinner fibrous elements and honeycomb-shaped matrix surrounding the fibers. When adult isolated cuticles were partially solubilized by several compounds, the structure revealed a strong insolubility and the main fibers were always observable. HPLC and spectrophotometric assays carried out to investigate the presence of tyrosine cross-linking, indicated such a mechanism as a key-element in the hardening process of the cuticle. Such data strongly suggest that the Gordius cuticle contains dityrosine compounds, whose formation is probably mediated by endogenous peroxidase activity. PMID- 11201277 TI - Postnatal development of the rat intrinsic cardiac nervous system: a confocal laser scanning microscopy study in whole-mount atria. AB - We used confocal laser scanning microscopy and fluorescent immunohistochemistry to study the developmental pattern and distribution of specific neuronal phenotypes within the intrinsic cardiac nervous system in whole-mount atrial preparations from newborn to 5 week old rats. Individual ganglia and neuronal cell bodies were localized by means of two general neuronal markers: protein gene product 9.5 (PGP) and microtubule-associated protein two (MAP). In rats < or =2 weeks old there were two main subpopulations of intrinsic neurons located in the intraatrial septum and around the origin of the superior vena cava. The more abundant was a population of strongly tyrosine hydroxylase (TH) immunoreactive (IR) neurons (10-40 microm in diameter) most of which were also PGP-IR. The second, less numerous (approximately 60-70% than the TH-IR group) type of neurons exhibited ChAT-IR which colocalized with MAP-IR. Towards the end of the second postnatal week and during the third, the ganglia containing these neurons became more numerous and their localization also included tissues around the origins of the inferior vena cava and the pulmonary veins, as well as both atrial walls close to the AV junction. During the second and third postnatal weeks, when the extrinsic innervation of the adrenergic and cholinergic phenotypes largely increases, the intrinsic innervation also changed greatly, and around the 21st postnatal day it appeared to acquire mature characteristics. The TH-IR neurons changed their characteristics and formed two types of ganglia. The larger ganglia containing large cells (20-40 microm in diameter) expressed TH-IR mostly close to their inner body surface (approximately 80-90% of identified neurons). Most of these neurons also expressed neuropeptide Y (NPY)-IR, specifically around their nuclei. The second type of small strongly TH-IR neurons (approximately 10% of all identified neurons) were contained in smaller groups (20-50 cells) which were usually embedded into much larger ganglia (100-400 cells), containing large (20 50 microm) neurons. Unlike all other intrinsic neurons, these small TH-IR cells did not exhibit any PGP-IR or MAP-IR. The number of ChAT-IR neurons increased at this stage, reaching approximately 90% of the neurons identified by the general neuronal markers. These neurons were surrounded by a rich network of cholinergic varicose nerve fibers, some of which were likely of an extrinsic origin. We have also identified relatively small ganglia expressing immunoreactivity to vasoactive intestinal polypeptide (VIP), and to substance P (SP). The presented data indicate that the phenotypes of intrinsic neurons in the rat heart change greatly during the first month of postnatal development. This may be at least partially related to the development and maturation of functional extrinsic nervous control of the heart. PMID- 11201278 TI - Integumental amino acid uptake in a carnivorous predator mollusc (Sepia officinalis, Cephalopoda). AB - The epithelial cells of the integument of body, arms and tentacles of Sepia officinalis present on their apical membrane a well-organised brush border and show the morphological and histochemical characteristics of a typical absorptive epithelium. The ability of the integument to absorb amino acids was investigated both in the arms incubated in vitro and in a purified preparation of brush border membrane vesicles (BBMV). Autoradiographic pictures of the integument after incubation of the arms in sea-water with or without sodium, showed that proline intake was Na+-dependent, whereas leucine intake appeared to be a largely cation independent process. Time course experiments of labelled leucine, proline and lysine uptakes in BBMV evidenced that these amino acids are accumulated within the vesicles in the presence of an inwardly directed sodium gradient. The sodium driven accumulation proves that cationic and neutral amino acids are taken up by the apical membrane of the epithelium of Sepia integument through a secondary active mechanism. For leucine, a 90% inhibition of the uptake was recorded in the presence of a large excess of the substrate. In agreement with the autoradiography results, an analysis of the cation specificity transport in BBMV showed that leucine uptake had a low cation specificity, whereas lysine and proline uptakes were Na+-dependent. An excess of lysine and proline, which share with alanine two different transport systems in the gill epithelium of marine bivalves, reduced eucine uptake. The possible role of the absorptive ability of the integument in a carnivorous mollusc is discussed. PMID- 11201279 TI - Impairment of adenylate cyclase activity and G-proteins in human uterine leiomyoma. AB - The mechanisms responsible for the growth of uterine leiomyoma (a frequent cause of infertility in women) are largely unknown. Some data supports that cAMP plays a role in the growth of uterine cells but there are no reports on the status of the cAMP producing system in this human benign neoplasia. In this study, biopsies from leiomyoma and the adjacent myometrium were taken from menstruating women subjected to total hysterectomy for leiomyoma. Adenylate cyclase activity was determined by a protein-binding method, and the expression of alpha(s), alphai1/2, alphai3 and alphai0) G-protein subunits was analysed by immunoblot. The leiomyoma samples exhibited a decreased expression of as and ai1/2 with respect to the adjacent myometrial tissue. No differences were observed in alphai3 and alphaio protein expression. The basal adenylate cyclase activity as well as the efficacy (as assessed by the maximal stimulation levels) of either forskolin or, to a lesser extent, Gpp[NH]p on stimulation the enzyme activity was significantly lower in leiomyoma than in myometrium, whereas the potency (as assessed by the ED50 values) of these two agents did not vary. Present data indicate that the human leiomyoma is associated with low levels of cAMP. It is conceivable that the loss of sensitivity of adenylate cyclase to endogenous regulatory molecules could be related to the pathogenesis of human leiomyomas given that cAMP inhibits the MAP-kinase cascade in uterine tissues. PMID- 11201280 TI - A new model for periostracum and shell formation in Unionidae (Bivalvia, Mollusca). AB - The periostracum in Unionidae consists of two layers. The outer one is secreted within the periostracal groove, while the inner layer is secreted by the epithelium of the outer mantle fold. The periostracum reaches its maximum thickness at the shell edge, where it reflects onto the shell surface. Biomineralization begins within the inner periostracum as fibrous spheruliths, which grow towards the shell interior, coalesce and compete mutually, originating the aragonitic outer prismatic shell layer. Prisms are fibrous polycrystalline aggregates. Internal growth lines indicate that their growth front is limited by the mantle surface. Transition to nacre is gradual. The first nacreous tablets grow by epitaxy onto the distal ends of prism fibres. Later growth proceeds onto previously deposited tablets. Our model involves two alternative stages. During active shell secretion, the mantle edge extends to fill the extrapallial space and the periostracal conveyor belt switches on, with the consequential secretion of periostracum and shell. During periods of inactivity, only the outer periostracum is secreted; this forms folds at the exit of the periostracal groove, leaving high-rank growth lines. Layers of inner periostracum are added occasionally to the shell interior during prolonged periods of inactivity in which the mantle is retracted. PMID- 11201281 TI - Isolation and partial characterization of myogenic cells from mussel larvae in vitro. AB - The main finding of the present study is the discovery of the possibility of a morphofunctional myogenic differentiation of larval mussel cells in vitro. The shape and extensive cytoskeletal network of the cultured contracting cells mimic largely those of smooth muscle cells in vivo. However, the behavior and protein composition of these cells are not completely identical with those of smooth muscle cells. Contracting mussel cells in vitro, as well as differentiated smooth muscles, demonstrate both phasic and tonic contractions. The paramyosin to myosin ratio in the cultured mussel cells is far less than that in the muscles of veliger larvae and adult mussels. We have found the protein carpets with various adhesive characteristics determine different development pathways. Myogenic differentiation is only observed in spreading cells. Non-spreading adherent cells plated on collagen carpet show high synthetic activity but the commitment of contractile phenotype is inhibited. Our results confirm that the myogenic program established in early embryogenesis of molluscs can be realized during the cultivation of cells from premyogenic larval stages. PMID- 11201282 TI - An ultrastructural study of connective tissue in mollusc integument: I. Bivalvia. AB - The ultrastructure of the subepidermal connective tissue (SEC) in different areas of the integument of the bivalves Callista chione, Pecten jacobaeus, Mytilus galloprovincialis and Ostrea edulis was studied by transmission electron microscopy. The main organisation of the SEC was broadly similar in all species: the SEC was connected to the epidermis by a basement membrane and merged directly with the deeper connective tissue surrounding muscles. The SEC was not differentiated into layers like the papillary and reticular dermis of mammals, however, the architecture, thickness and shape of the basement membrane varied from species to species, as well as within species (in the foot, central or marginal zones of the mantle). The ultrastructure of the lamina densa was broadly similar to that in mammals: although basotubules and double pegs were absent, proteoglycans and rod-like units homologous to 'double tracks' were always abundant. A zone similar to the lamina lucida was irregularly present and was shot thorough with small protrusions of the lamina densa that connected with the epithelial hemidesmosomes or focal adhesions. Nevertheless zones were observed where the lamina densa fuse directly to the epithelial plasmamembrane. This variability of connection may be related to the various types of epidermal cell. A lamina fibroreticularis was not recognized since anchoring fibrils and microfibrils were not present; lamina densa protrusions into the extracellular matrix (ECM) of SEC characterize the connection between basement membrane and SEC. Collagen fibrils were small and of constant diameter and were never organised into fibres. Anchoring devices - similar to the anchoring plaques of mammalian dermis - were abundant and scattered between SEC collagen fibrils. The orange-pink pigmentation of C. chione seems due to electron-dense granules embedded within the connective ECM. PMID- 11201283 TI - Lipopolysaccharide-dependent induction of leech leukocytes that cross-react with vertebrate cellular differentiation markers. AB - We have designed experiments to characterise leech leukocytes that mediate inflammatory responses. Shortly after inflicting injury to the body wall in the presence of lipopolysaccharides, many cells resembling macrophages, NK cells and granulocytes of vertebrates and many invertebrates migrated to the lesioned area. Nuclei of migrating cells incorporated bromodeoxyuridine. Using human monoclonal antibodies, macrophage-like cells were positive for CD25, CD14, CD61, CD68, CD11b and CD11c. NK-like cells were positive for CD25, CD56, CD57 and CD16, and granulocytes were positive for CD11b and CD11c. In blots of leech extracts, the CD25 monoclonal antibody recognised a band of about 55 kD; the CD56 monoclonal antibody, two bands of about 140 and 210 kD; the CD57 monoclonal antibody, two bands of about 106 and 70 kD; the CD14 monoclonal antibody, a band of about 50 kD; the CD16 monoclonal antibody, a band of about 60 kD. CD61 and CD68 both recognised a band of about 110 kD; CD11b recognised a band of 200 kD, and CD11c, a band of 180 kD. PMID- 11201284 TI - The MDCK cell line is made up of populations of cells with diverse resistive and transport properties. AB - The MDCK cell line has been used as a model for the renal distal tubule. When grown on permeable supports, the cells form tight junctions and transport sodium and calcium. Widely different values have, however, been obtained for resistance and transports by different investigators. Since the MDCK cell line is genetically heterogeneous, one potential reason for observed differences is the use of different populations of cells. Dilutional techniques have been used to obtain eleven MDCK cell clones. The clones exhibit a range of values for resistance (300-4000 ohms cm2), net Ca2+ transport (3.2-81 pmol/cm2/min) and net Na+ transport (0.4-6.0 nmol/cm2/min). To determine if the characteristics of clonal cell lines changed with increasing passage number, resistance was measured at relatively early and late passage number. Resistance increased with increasing passage number in two of six lines and decreased in one. These studies demonstrate that differences between previous studies may be due to differences in cell population, length of time since passage, and passage number. Clonal cell lines should provide a useful tool to investigate ion transport and mechanisms of regulation of transport in this model of renal distal tubule. PMID- 11201285 TI - Refining procedures for the administration of substances. Report of the BVAAWF/FRAME/RSPCA/UFAW Joint Working Group on Refinement. British Veterinary Association Animal Welfare Foundation/Fund for the Replacement of Animals in Medical Experiments/Royal Society for the Prevention of Cruelty to Animals/Universities Federation for Animal Welfare. PMID- 11201286 TI - Metabolic flux measurements across portal drained viscera, liver, kidney and hindquarter in mice. AB - A method was developed to measure metabolic fluxes across either portally-drained viscera (PDV) and liver or kidney and hindquarter (HQ) in anesthetized mice. The method includes a primed-constant infusion of ketamine-medetomidine anaesthesia to stabilize the mice for the surgical procedures. For measurement of metabolic fluxes across PDV and liver, blood sampling catheters were inserted in the carotid artery, portal vein and hepatic vein and infusion catheters in the jugular vein and mesenteric vein. For measurement of metabolic flux across kidney and HQ, blood sampling catheters were inserted in the carotid artery, renal vein and caval vein and infusion catheters in the jugular vein and abdominal aorta. 14C-PAH was infused to enable plasma flow measurement using an indicator dilution method. In addition, we developed a blood sampling procedure without waste of blood. We measured plasma flow and metabolic fluxes across PDV, liver, kidney and HQ. Mean plasma flow in post-absorptive mice was: PDV: 0.9+/-0.2, liver: 1.2+/ 0.3, kidney: 1.0+/-0.1, HQ: 1.1+/-0.3 ml/10 g body weight (b.w.)/min. Significant glutamine release by the HQ and uptake of glutamine by the kidney and PDV was observed. In PDV, citrulline is produced from glutamine and is in turn used by the kidney for the production of arginine. In conclusion, the described model enables measurement of metabolic fluxes across PDV, liver, kidney and HQ in mice. The availability of such a small animal model allows the potential for measuring metabolic parameters in transgenic and knockout mice, and therefore may lead to an important refinement in metabolic research. PMID- 11201287 TI - Evaluation of individually ventilated cage systems for laboratory rodents: occupational health aspects. AB - New ventilated caging systems for laboratory animals were compared with conventional caging regarding allergen distribution, ergonomic suitability, cage environment and animal welfare. This paper presents occupational health evaluations. Mice were placed in individually ventilated cage (IVC) systems, a ventilated cabinet, and in cages on open shelves (conventional husbandry). The IVC systems were studied at negative and positive airflow. Aeroallergens were sampled on filters (n = 204, including controls) in undisturbed rooms and during cage changing. Concentrations of mouse urinary allergen (Mus m 1) in filter eluates were measured using sandwich ELISA. An ergonomic evaluation was performed with measurement of traction forces. Staff exposure during cage changing was high in all systems, range 116-4430 ng Mus m 1/m3. In undisturbed animal rooms, allergen levels were orders of magnitude higher when using conventional caging compared with ventilated systems; P < 0.001. At positive pressure both IVCs leaked allergen (median Mus m 1 concentration was < 0.08 ng/m3 at negative, but 6.5 ng/m3 (IVC1) and 0.8 ng/m3 (IVC2S) at positive pressure). The IVC systems had ergonomic disadvantages compared with the conventional husbandry and the ventilated cabinet, for instance with cages in unsuitable working heights. Ventilated husbandry solutions reduce levels of airborne allergen substantially at negative pressure, but are ergonomically less suitable. To prevent allergen exposure during cage changing, we propose that this procedure should be performed under ventilated conditions. Producers and users must cooperate in optimizing animal caging systems for both animals and staff. PMID- 11201288 TI - Evaluation of individually ventilated cage systems for laboratory rodents: cage environment and animal health aspects. AB - The use of individually ventilated cage (IVC) systems has become an attractive housing regime of laboratory rodents. The benefits of IVC systems are, reportedly, a high degree of containment combined with relative ease of handling, and a high degree of protection from allergenes. In the present study we tested whether two IVC systems (BioZone VentiRack, IVC1 and Techniplast SealSafe, IVC2S), in which we held mature male NMRI mice, were constructed to maintain a constant differential pressure, positive or negative, during a prolonged period of time. We also measured ammonia (NH3) concentrations after about 2 weeks of use, and CO2 build-up during a 60 min simulated power failure situation. In addition, animal weight development and bite-wound frequency were recorded (Renstrom et al. 2000). From the present study it is concluded that the IVC1 air handling system provides a more uniform and balanced differential pressure than the IVC2S. Both systems effectively scavenge NH3 when bedding material is not soaked by urine. Although the IVCs are dependent on the continual function of the fans to work properly, it seems unlikely that CO2 concentrations increase to hazardous levels, as a result of a one hour power failure, with the type of cages used in this study. Differences in weight development and bite-wound occurrence were noted between the two IVC systems. Causes for these differences could not be established and need more investigation. PMID- 11201289 TI - The impact of reduced frequency of cage changes on the health of mice housed in ventilated cages. AB - Our purpose in this investigation was to determine if we could reduce cage changing frequency without adversely affecting the health of mice. We housed mice at three different cage changing frequencies: 7, 14, and 21 days, each at three different cage ventilation rates: 30, 60 and 100 air changes per hour (ACH), for a total of nine experimental conditions. For each condition, we evaluated the health of 12 breeding pairs and 12 breeding trios of C57BL/6J mice for 7 months. Health was assessed by breeding performance, weanling weight and growth, plasma corticosterone levels, immune function, and histological examination of selected organs. Over a period of 4 months, we monitored the cage microenvironment for ammonia and carbon dioxide concentrations, relative humidity, and temperature one day prior to changing the cage. The relative humidity, carbon dioxide concentrations, and temperature of the cages at all conditions were within acceptable levels. Ammonia concentrations remained below 25 ppm (parts per million) in most cages, but, even at higher concentrations, did not adversely affect the health of mice. Frequency of cage changing had only one significant effect; pup mortality with pair matings was greater at the cage changing frequency of 7 days compared with 14 or 21 days. In addition, pup mortality with pair matings was higher at 30 ACH compared with other ventilation rates. In conclusion, under the conditions of this study, cage changes once every 14 days and ventilation rates of 60 ACH provide optimum conditions for animal health and practical husbandry. PMID- 11201290 TI - The cage preferences of laboratory rats. AB - Preference tests were used to assess a range of enrichment options for rats kept under standard New Zealand (and similar) caging conditions. The rats did not show significant preferences for most of the options, over an empty cage. The exceptions were shredded paper, a nesting box and a semi-enriched condition incorporating a range of modifications. These cage modifications are recommended for the enrichment of laboratory rats. PMID- 11201291 TI - Estimates of appropriate number of rats: interaction with housing environment. AB - An extensive list of physiological parameters from previous experiments was re analysed in order to evaluate the effects of enrichment, cage type and group size on the within-group variation and hence on the number of animals needed in studies using Wistar rats. The independent factors studied in these experiments included the provision of aspen gnawing blocks for enrichment, solid bottom cages (SBCs) and grid floor cages (GFCs) and animal number per cage (varied from 1-4). SOLO power analysis was used to calculate the smallest number of animals (n) needed to detect an arbitrarily chosen 20% effect size, when significance was set at P = 0.05 and statistical power at 0.90. N ratios (nlarger/nsmaller) were calculated for the effect of enrichment, cage type and group size to compare the 'treatment group' with the 'control group'. The n values of adrenal gland, interscapular brown adipose tissue (BAT) and epididymal adipose tissue (EAT) weights seemed to vary most, whereas final body weight (FBWJ and growth seemed to be the least variable ones. According to one-sample t-test, the N ratios of most physiological parameters differed significantly from zero (except the ones of FBW) indicating that n values in 'treatment' and 'control' groups were unequal. The results indicate that some of the physiological parameters are susceptible to variability attributable to environmental modifications in general whereas some are not. Furthermore, they suggest that the variation of different parameters may vary from one experiment to another and between different environments thus hindering the estimations of appropriate number of animals. PMID- 11201292 TI - Strain differences in some immune parameters can be obscured by circadian variations and laboratory routines: studies of male C57BL/6J, Balb/c and CB6 F1 mice. AB - This is a report on the potential influence of circadian changes and laboratory routines on some immune parameters (thymic and splenic weights, the numbers of bone marrow, peripheral blood, and peritoneal leukocytes) in: (1) males of C57BL/6J, Balb/c, and CB6 F1 mice kept under identical laboratory conditions; (2) males of CB6 mice kept under the same laboratory conditions, except for opposite light/dark regimes, either light/dark (LD) or dark/light (DL). All the animals were purchased from the same supplier and adapted for 4-5 weeks to strictly controlled housing conditions. Some parameters were similar at certain time points but statistically significantly different at others due to strain-specific daily variations. In order to make the interstrain comparisons more reliable, the data collected around the day/night cycle were pooled for calculations of mean values. Several immune parameters of CB6 mice kept under DL conditions were significantly different than those in mice under the conventional LD conditions. In conclusion, the extrapolation of results (especially in the field of neuroimmunology) to other strains (or species) should be done with great caution; and all interstrain (interspecific) comparisons, especially those from various laboratories, should always be related to specific time points and laboratory conditions. PMID- 11201293 TI - The role of cyclooxygenase and lipoxygenase in cancer chemoprevention. AB - The involvement of prostaglandins (PGs) and other eicosanoids in the development of human cancer has been known for over two decades. Importantly, an increase in PG synthesis may influence tumor growth in human beings and experimental animals, and numerous studies have illustrated the effect of PG synthesis on carcinogen metabolism, tumor cell proliferation and metastatic potential. PGs produced by cyclooxygenases (COXs) are represented by a large series of compounds that mainly enhance cancer development and progression, acting as carcinogens or tumor promoters, with profound effects on carcinogenesis. Further investigations suggest that arachidonic acid (AA) metabolites derived from lipoxygenase (LOX) pathways play an important role in growth-related signal transduction, implying that intervention through these pathways should be useful for arresting cancer progression. We discuss here the implications of COX and LOX in colon, pancreatic, breast, prostate, lung, skin, urinary bladder and liver cancers. Select inhibitors of COX and LOX are described, including nonsteroidal antiinflammatory drugs (NSAIDs), selective COX-2 inhibitors, curcumin, tea, silymarin and resveratrol, as well as a method useful for evaluating inhibitors of COX. Although a substantial amount of additional work is required to yield a better understanding of the role of COX and LOX in cancer chemoprevention, it is clear that beneficial therapeutic effects can be realized through drug-mediated modulation of these metabolic pathways. PMID- 11201294 TI - The micronutrient indole-3-carbinol: implications for disease and chemoprevention. AB - This review provides a historical perspective for the development of indole-3 carbinol (I-3-C) as a chemopreventive or therapeutic agent. Early experiments in animal models clearly showed that feeding cruciferous vegetables reduced the incidence of chemical carcinogenesis. Excitement was generated by the finding that these vegetables contained a high content of indole-containing compounds, and I-3-C could by itself inhibit neoplasia. The mechanism of action was linked primarily to the ability of I-3-C and derived substances to induce mixed-function oxidases and phase II antioxidant enzymes by binding and activating the aryl hydrocarbon receptor. Most of the literature on chemoprotection by dietary indole compounds relates to this mechanism of action. Other mechanisms, however, are notable for this class of compounds, including their ability to act as radical and electrophile scavengers; the various ascorbate conjugates of I-3-C (ascorbigens) may be important in this regard. Exciting recent findings have demonstrated that I-3-C and its reaction products can affect cellular signaling pathways, regulate the cell cycle, and decrease tumor cell properties related to metastasis. It does not appear that I-3-C per se is the primary active compound in chemoprotection or chemoprevention. Rather, I-3-C and ascorbate provide the parent compounds for the formation of a myriad of nonenzymatic reaction products that have strong biological potency. We conclude with our thoughts regarding the current status and future directions for the use of I-3-C and related compounds. PMID- 11201295 TI - Carotenoids and chronic diseases. AB - Chronic diseases such as cancer and cardiovascular diseases are the major causes of deaths in North America. Dietary intake of fruits and vegetables has been suggested to have protective effects against such chronic diseases. Carotenoids are important plant pigments which are thought to contribute towards the beneficial effects of fruit and vegetable consumption. This review focuses on the role of carotenoids and particularly lycopene in chronic diseases. PMID- 11201296 TI - The bioactivity of saponins: triterpenoid and steroidal glycosides. AB - Triterpenoid and steroidal glycosides, referred to collectively as saponins, are bioactive compounds present naturally in many plants. They have considerable potential as pharmaceutical and/or nutraceutical agents in natural or synthetic form. Saponins, from a variety of sources, have been shown to have hypocholesterolemic, anti-coagulant, anticarcinogenic, hepatoprotective, hypoglycemic, immunomodulatory, neuroprotective, anti-inflammatory and anti oxidant activity. This paper reviews saponin research of the last decade, focussing on developments in understanding their mechanism of action and structure-activity relationships. Virtually all of this work has used animal and in vitro models. To date there are very few human data. PMID- 11201297 TI - Effect of organosulfur compounds from garlic and cruciferous vegetables on drug metabolism enzymes. AB - The frequent consumption of cruciferous vegetables and garlic is associated with several health benefits. These foods contain organosulfur compounds that are known to affect the biotransformation of xenobiotics, and therefore can influence the toxicity and carcinogenicity of environmental chemicals. In this article, we review the effects of isothiocyanates and diallyl sulfide on xenobiotic metabolism and the enzymes involved in the process. Isothiocyanates and diallyl sulfide can modulate the levels of phase I and phase II drug-metabolizing enzymes by affecting the transcriptional rates of their genes, the turnover rates of specific mRNAs or enzymes, or the enzyme activity. These compounds are not general enzyme inhibitors or inducers. They elicit selectivity in their mode of action. Elucidating the mechanisms involved in the alteration of drug metabolizing enzymes by isothiocyanates and diallyl sulfide will increase our understanding of their possible effects on the biotransformation of drugs as well as the potential beneficial or detrimental effects of these organosulfur compounds. PMID- 11201298 TI - Molecular aspects of procyanidin biological activity: disease preventative and therapeutic potentials. AB - There is a growing interest in the utilization of procyanidins for their dietary and pharmacological properties. A wide spectrum of beneficial activity for human health has been advocated for procyanidins due, in part, to their strong antioxidant activity. More recently the ability of procyanidins to affect gene expression and cell response in vitro has been reported, providing a novel mechanistic perspective on the biological activity of these phytochemicals. This article reviews recent cellular and molecular aspects of the biological activity of procyandins and discusses their disease preventative and therapeutic potentials. PMID- 11201299 TI - Promotion of health by soy isoflavones: efficacy, benefit and safety concerns. AB - Cardiovascular diseases, osteoporosis-related hip fractures, and various cancers of the colon, prostate, uterus, and breast are remarkably less prevalent in Asia than in other industrialized countries. It is believed that the large consumption of soy products in Asian countries is contributory to the reduction of these chronic disorders. Genistein is a major isoflavone found in most soy products and plays an important role in the promotion of human health. Extensive epidemiological, in vitro, and animal studies have been performed, and most studies indicate that genistein has beneficial effects on a multitude of human disorders, including cancers, cardiovascular diseases, osteoporosis, and postmenopausal symptoms. To date, there is an abundance of promising studies supporting genistein's potential uses, but further research is still needed to validate its preventative and therapeutic efficacy. In addition, the adverse effects of genistein have drawn public attention. More studies are required to assess the potential detrimental effect of genistein, and a benefit-risk ratio should be considered before future clinical studies are performed. PMID- 11201300 TI - Bioavailability of flavonoids and potential bioactive forms in vivo. AB - Flavonoids are powerful antioxidants in vitro, but their overall functions in vivo have yet to be clarified, whether antioxidant, anti-inflammatory, enzyme inhibitor or inducer, or some other role. The reducing properties of flavonoids might also contribute to redox regulation in cells independently of their antioxidant properties. However, in order to understand their bioactivity in vivo, it is necessary to understand the factors influencing the absorption of flavonoids by the gastrointestinal tract, the nature of the conjugates and metabolites in the circulation and how this influences their antioxidant activities. PMID- 11201301 TI - Chemoprotection by organosulfur inducers of phase 2 enzymes: dithiolethiones and dithiins. AB - One of the major mechanisms of protection against carcinogenesis, mutagenesis, and other forms of toxicity mediated by carcinogens is the induction of enzymes involved in their metabolism, particularly phase 2 enzymes such as glutathione S transferases, UDP-glucuronosyl transferases, and quinone reductases. Animal studies indicate that induction of phase 2 enzymes is a sufficient condition for obtaining chemoprevention and can be achieved by administering any of a diverse array of naturally-occurring and synthetic chemopreventive agents. Alliaceous and cruciferous plants are rich in organosulfur compounds with inducer activity. Indeed, monitoring of enzyme induction has led to the recognition or isolation of novel, potent chemopreventive agents such as 1,2-dithiole-3-thiones, dithiins and the isothiocyanate sulforaphane. For example, oltipraz, a substituted 1,2 dithiole-3-thione originally developed as an antischistosomal agent, possesses chemopreventive activity against different classes of carcinogens targeting multiple organs. Mechanistic studies in rodent models for chemoprevention of aflatoxin B1 (AFB1)-induced hepatocarcinogenesis by oltipraz indicates that increased expression of phase 2 genes is of central importance, although inhibition of phase 1 activation of aflatoxin B1 can also contribute to protection. Exposure of rodents to 1,2-dithiole-3-thiones triggers nuclear accumulation of the transcription factor Nrf2 and its enhanced binding to the Antioxidant Response Element, leading to transcriptional activation of a score of genes involved in carcinogen detoxification and attenuation of oxidative stress. Nrf2-deficient mice fail to induce many of these genes in response to oltipraz and the impact of this genotype on the chemopreventive efficacy of dithiolethiones is currently under investigation. To test the hypothesis that enzyme induction is a useful strategy for chemoprevention in humans, three key elements are necessary: a candidate agent, an at-risk population and modulatable intermediate endpoints. Towards this end, a placebo-controlled, double blind clinical trial of oltipraz was conducted in residents of Qidong, P.R. China who are exposed to dietary aflatoxins and who are at high risk for the development of liver cancer. Oltipraz significantly enhanced excretion of a phase 2 product, aflatoxin-mercapturic acid, a derivative of the aflatoxin-glutathione conjugate, in the urine of study participants administered 125 mg oltipraz by mouth daily. Administration of 500 mg oltipraz once a week led to a significant reduction in the excretion of the primary oxidative metabolite of AFB1, aflatoxin M1, when measured shortly after drug administration. While this study highlighted the general feasibility of inducing phase 2 enzymes in humans, a longer term intervention is addressing whether protective alterations in aflatoxin metabolism can be sustained for extended periods of time in this high-risk population. Food based approaches to chemoprotection, targeted both to the general population and high-risk individuals, offer many practical advantages compared to the use of pharmaceutical agents. Thus, identification and utilization of naturally occurring organosulfur chemoprotectors including dithiins should be a high priority. PMID- 11201302 TI - Cancer chemoprevention and apoptosis mechanisms induced by dietary polyphenolics. AB - This review summarises current knowledge on the various molecular chemopreventive or therapeutic mechanisms that may be involved when the administration of flavonoids or polyphenols prevented chemical carcinogenesis in animal models. These mechanisms can be subdivided into the following: 1) the molecular mechanisms involved in preventing carcinogen metabolic activation, 2) the molecular mechanisms for preventing tumour cell proliferation by inactivation or downregulation of prooxidant enzymes or signal transduction enzymes, 3) the molecular cell death mechanisms for the induction of tumour cell death (apoptosis) and the molecular mechanisms for the inhibition of isolated mitochondria functions. Many of the flavonoids and polyphenols found in diets, supplements or herbal medicine were also ranked using "accelerated cytotoxic mechanism screening" by a combinatorial approach utilising isolated rat hepatocytes. A strong correlation of an early collapse of the mitochondrial membrane potential and cell death was found for most of the cytotoxic polyphenols but did not occur with non-toxic polyphenols. This screening could prove useful for eliminating polyphenols that have the potential for adverse health effects and for selecting safe and effective polyphenolic candidates for further development as supplements for preventing cancer or cardiovascular disease. Safety concerns of flavonoid/polyphenol supplements are also reviewed. PMID- 11201303 TI - Effect of the grapefruit flavonoid naringin on pharmacokinetics of quinine in rats. AB - The effect of the grapefruit flavonoid naringin, an inhibitor of CYP3A4, on the pharmacokinetics of quinine in rats after oral or intravenous (i.v.) dosing of quinine was investigated. Female Wistar rats (wt 190-220 g) were used in two separate studies, i.e. oral and i.v. administration of quinine. The animals were divided into two groups, one served as control and the other group was pretreated with 25 mg/kg naringin once a day for 7 consecutive days before the pharmacokinetic study. On the study day, quinine (25 mg/kg) was administered to the rats by either the oral or i.v. route. Blood samples were collected at different times, up to 6 h after quinine administration. Plasma quinine concentration was assayed by HPLC. Pretreatment with naringin did not cause any significant change in the pharmacokinetics of quinine after the i.v. dose. However pretreatment with naringin led to a 208% increase in peak plasma concentration (Cmax), a 93% increase in time to reach Cmax (tmax), and a 152% increase in the area under the plasma concentration-time curve (AUC) of quinine after oral administration. Consequently, the oral bioavailability of quinine was significantly increased (p < 0.05) from 17% (control) to 42% after pretreatment with naringin. There was no significant difference in the elimination half-life (t(1/2)beta) of quinine between the two groups. These results suggest that pretreatment with the grapefruit flavonoid naringin is associated with increased oral bioavailability of quinine in rats. PMID- 11201304 TI - Organosulfur compounds from Allium and the chemoprevention of cancer. AB - Allium vegetables and their associated organosulfur constituents are extensively studied for their chemopreventive potential against cancer. This article overviews their anticarcinogenic and antigenotoxic properties. Epidemiological studies (mostly case-control studies) provide strong evidence that Allium vegetable consumption reduces the incidence of gastric and colon cancer while the association between Allium vegetable consumption and other cancers is less convincing. Furthermore, many experimental studies have demonstrated that organosulfur compounds and Allium extracts have inhibitory effects on carcinogenesis in animals. These inhibitory effects are supported by many diverse mechanisms, including inhibition of carcinogen formation, modulation of carcinogen metabolism, inhibition of mutagenesis and genotoxicity, inhibition of cell proliferation and increase of apoptosis, inhibition of angiogenesis, and immune system enhancement. Before such constituents or extracts can be used in chemopreventive trials, it is important to verify their lack of toxicity and to investigate further their precise mechanisms of action throughout the whole process of carcinogenesis. PMID- 11201305 TI - Allyl sulfides modify cell growth. AB - Extensive evidence points to the ability of allyl sulfides from garlic to suppress tumor proliferation both in vitro and in vivo. This antineoplastic effect is generally greater for lipid-soluble than water-soluble allyl sulfides. Both concentration and duration of exposure can increase the antiproliferative effects of lipid- and water-soluble allyl sulfides. Part of their antiproliferative effects may relate to an increase in membrane fluidity and a suppression of integrin glycoprotein IIb-IIIa mediated adhesion. Alterations in cholesterol, arachidonic acid, phospholipids and/or thiols may account for these changes in membrane function. Allyl sulfides are also recognized for their ability to suppress cellular proliferation by blocking cells in the G2/M phase and by the induction of apoptosis. This increase in the G2/M and apoptotic cell populations correlates with depressed p34cdc2 kinase activity, increased histone acetylation, increased intracellular calcium and elevated cellular peroxide production. While impressive pre-clinical data exist about the antineoplastic effects of allyl sulfur compounds, considerably more attention needs to be given to their effects in humans. The composition of the entire diet and a host of genetic/epigenetic factors will likely determine the true benefits that might arise from allyl sulfur compounds from garlic and other Allium foods. PMID- 11201306 TI - Amifostine: mechanisms of action underlying cytoprotection and chemoprevention. AB - Amifostine is an important drug in the new field of cytoprotection. It was developed by the Antiradiation Drug Development Program of the US Army Medical Research and Development Command as a radioprotective compound and was the first drug from that Program to be approved for clinical use in the protection of dose limiting normal tissues in patients against the damaging effects of radiation and chemotherapy. Its unique polyamine-like structure and attached sulfhydryl group give it the potential to participate in a range of cellular processes that make it an exciting candidate for use in both cytoprotection and chemoprevention. Amifostine protects against the DNA damaging effects of ionizing radiation and chemotherapy drug associated reactive species. It possesses anti-mutagenic and anti-carcinogenic properties. At the molecular level, it has been demonstrated to affect redox sensitive transcription factors, gene expression, chromatin stability, and enzymatic activity. At the cellular level it has important effects on growth and cell cycle progression. This review focuses on relating its unique chemical design to mechanisms of action that underlie its broad usefulness as both a cytoprotective and chemopreventive agent for use in cancer therapy. PMID- 11201307 TI - Determination of nicotine N-1-glucuronide, a quaternary N-glucuronide conjugate, in human biological samples. AB - [Methyl-d3]-N-1-beta-D-glucopyranosyl-(+/-)-nicotinium inner salt ((+/-)-[methyl d3]nicotine N-1-glucuronide) was synthesized from (+/-)-[methyl-d3]nicotine via reaction with methyl-2,3,4-tri-O-acetyl-1-bromodeoxy-alpha-D-glucopyranouronate, followed by deprotection with 1 M aqueous NaOH and purification by preparative TLC. Nicotine N-glucuronide was identified and determined directly in smokers' urine. A solid phase extraction method was used to partially isolate the material from urine. Subsequent determination was by thermospray-LC/MS using the synthetic d3-labeled nicotine N-glucuronide as internal standard. The identified urinary component had the same retention time as a synthetic standard and gave the same mass spectrum. The thermospray mass spectrum was characterized from the protonated molecular ion (m/z 339) and the protonated aglycone ion (m/z 163). Quantitative results from this direct method were compared with those from an indirect method, which calculated the nicotine glucuronide in the biological sample from the amount of nicotine released following treatment of the sample with the deconjugating enzyme, beta-glucuronidase. On average, the concentration of nicotine N-glucuronide determined by the direct method was 34% greater than that determined by the indirect method. Concentrations of nicotine N-glucuronide in urine ranged from 2.2 to 7.6 nmol/ml with a limit of detection of 1.3 nmol/ml. PMID- 11201308 TI - Effect of black tea on lipid peroxide and glutathione levels in female rats. AB - The effects of black tea (Camellia sinensis L.) on lipid peroxidation and glutathione (GSH) levels in carbon tetrachloride (CCl4)-treated female Wistar rats were examined. Two control groups and one treatment group were tested. The control groups were fed with a standard diet, while the black tea group was fed the standard diet plus 6% by weight dried black tea leaves. At the end of 2 months, a single dose of CCl4 (1 ml/kg, i.p.) in olive oil was administered to rats in one of the control groups and the black tea group. They were sacrificed after 2 hours. Rats in the other control group were administered olive oil in a similar fashion. Measurements were made of lipid peroxide levels in liver and plasma, glutathione levels in liver, and alanine transaminase (ALT) and aspartate transaminase (AST) activities in plasma. Liver lipid peroxide levels, plasma ALT and AST activities were significantly decreased in the black tea group compared with the CCl4-treated control group, while plasma lipid peroxide levels were not. These results are parallel to those previously found with Wistar male rats. Glutathione levels, however, were not significantly affected, in contrast to the data relating to male rats, either after CCl4 or black tea treatments. The results of our study add to the findings that black tea attenuates CCl4-induced hepatic injury but also indicates the susceptibility of glutathione levels to endocrinological effects. PMID- 11201309 TI - Modelling human cytochromes P450 for evaluating drug metabolism: an update. AB - Cytochrome P450 (CYP) enzymes represent the major catalysts for the Phase 1 metabolism of drugs and other xenobiotics in Mammalia, including Homo sapiens. There is considerable current interest in evaluating and, consequently, predicting the metabolic fate of new chemical entities (NCEs) via modelling molecular interactions with P450 constructs, such that sites of metabolism, particular CYP involvement and binding affinities, can be estimated. This paper focuses on the principles for homology modelling of typical enzyme-substrate interactions within the putative active sites of major P450s associated with drug metabolism in man. It also represents an update on previously published work in this journal /1/. PMID- 11201310 TI - Course of neuropsychological recovery from moderate-to-severe head injury: a 2 year follow-up. AB - Neuropsychological outcome and recovery of a group of 91 patients with moderate to-severe head injuries were prospectively investigated over a 2 year period, with evaluations at acute hospital discharge at 6 months and 2 years post-injury. A group of 39 trauma patients with injuries to parts of the body other than the head were used as controls. The head injured group performed significantly worse than the control group at baseline, 6 months and 2 years post-injury. Significant improvement was found during the first 6 months, but also between 6 months and 2 years post-injury. Trauma controls also performed significantly better at 6 months post-injury compared to baseline. Differential practice effects between groups cause difficulties in determining recovery. Within the head injured group, three distinct recovery groups were identified varying as a function of coma length and coma-duration. The first group is comparable with the trauma controls. The other two groups demonstrate significant neuropsychological impairments at baseline, with one group showing a marked improvement over the 2 year period, and the other group showing only small improvement over this time period. PMID- 11201311 TI - Stability of employment after brain injury: a 7-year follow-up study. AB - Forty-three patients with severe traumatic brain injury (n = 24), cerebrovascular diseases (n = 15), or other acquired brain damage (n = 4) were followed-up 7-8 years after neuropsychological rehabilitation including a vocational re-entry programme. Current vocational status and work history since rehabilitation were investigated by means of a structured interview. Before interview, the patients were classified on the basis of medical records into four groups: (A) patients with minor residual neuropsychological impairments, (B) patients with minor impairments but psychopathological symptoms, (C) patients with persistent neuropsychological impairments showing no psychopathological symptoms, and (D) patients with persistent impairments and psychopathological symptoms. For patients in group A, a good, and for those in group D, a poor long-term employment outcome was predicted, while no predictions were made for the intermediate groups. Of the 43 interviewed subjects, 16 (37%) reported a stable return to work at pre-morbid level and seven (16%) at a lower level. In eight patients (19%), persisting difficulties in maintaining work were documented. Twelve subjects (28%) had retired within a period of 2 years after work trial. The relationship between patient classification and long-term employment outcome was only weak. Four out of 11 patients with a good prognosis (group A) experienced vocational adjustment problems or had retired. Three out of 10 patients with a poor prognosis (group D) were able to continue successfully with their previous jobs. These cases are described in detail. The employment outcome of the intermediate groups was very heterogeneous. The results suggest that particular attention should be paid to the long-term consequences of a reduced capacity for work, even if minor in degree. The success of patients despite a poor prognosis illustrate unsolved problems in relation to the ecological validity of neuropsychological measures of executive dysfunctions. PMID- 11201312 TI - Neuropsychological rehabilitation for traumatic brain injury: do carers benefit? AB - This study evaluated the effectiveness of a new rehabilitation service, compared with existing services, for carers of people with traumatic brain injury (TBI). Subjects were 96 adult carers of people consecutively admitted to two local hospitals. They were assigned to one of three groups: Early new service (pre discharge); Late new service (post-discharge); or a Control condition (existing services only). Individual randomization was not possible and randomization by hospital site was rejected because of demographic and clinical differences between sites. Group assignment was determined by a pre-specified timetable which alternated between hospitals. Two outcomes were compared at 6 months post-injury: carers' emotional distress and how well-informed they felt about TBI and available resources. Analyses adjusting for potential confounding factors confirmed a clinically plausible superior outcome for both intervention groups compared to the control group. However, these differences did not obtain statistical significance (p > or = 0.01). Several reasons for these findings are discussed, including the novelty of the new service and methodological issues such as statistical power. Longer term follow-up studies are required as psychological sequelae and, therefore, the need for intervention is known to increase with time and may not be most apparent during the first 6 months. PMID- 11201313 TI - Errors in diagnosing post-traumatic stress disorder after traumatic brain injury. AB - Evidence to support the view that post-traumatic stress disorder (PTSD) can occur after traumatic brain injury (TBI) continues to grow. However, the reported incidence of cases with both diagnoses ranges widely, from less than 1% to more than 50%. Given that the incidence of TBI is high, a more precise incidence has to be established if screening and treatment resources are to be considered. Are cases being missed or are they over-diagnosed? The single case report presented here does not definitively answer this question, but illustrates the potential shortcomings of diagnosing PTSD using questionnaire measures alone (Impact of Events Scale, Post-traumatic Stress Diagnostic Scale and General Health Questionnaire) and indicates a need for a conjoint interview which takes into account the common effects of TBI and the symptom overlap between PTSD and TBI. PMID- 11201314 TI - Location of the chronic subdural haematoma: role of the gravity and cranial morphology. AB - Chronic subdural haematoma (SDH) frequently originates from subdural hygroma (SDG). The cranial morphology can determine the location of SDG. Since SDG is the precursor of chronic SDH, the shapes of the cranium wall act an important role in location of chronic SDH. The authors tried to test this hypothesis. The computed tomographic scans or magnetic resonance images of 118 consecutive patients with chronic SDH were re-evaluated, and the symmetry of the cranium and location of the lesion were checked. The cranium was symmetrical in 55 patients (47%) and asymmetrical in 63 patients (53%). Chronic SDH was bilateral in 25 patients (21%) and unilateral in 93 patients (79%). It was more commonly bilateral in symmetrical craniums than in asymmetrical craniums (29.1% vs. 14.3%) (p = 0.0496). In 63 patients with asymmetric cranium, the chronic SDH was bilateral in nine patients, located on the opposite side of the flat side in 38 patients, and located on the same side of the flat side in 17 patients. This unequal distribution was statistically significant (p = 0.03). In four patients, the haematoma originated from the acute SDH located on the same side of the flat side. No reason could be found in the remaining 13 patients. Chronic SDH originating from SDG usually locates on the opposite to the flat side of the skull. The shape and posture of the cranium can predict the location of chronic SDH, as in the SDG. PMID- 11201315 TI - Pre-injury crime, substance abuse, and neurobehavioural functioning after traumatic brain injury. AB - There is limited information regarding the effects of pre-injury history of arrest or history of substance use on neurobehavioural functioning after brain injury. The current study included 211 patients with traumatic brain injury, who were seen for a follow-up neuropsychological evaluation in an outpatient setting. An effort was made to distinguish between (1) patients with a history of pre injury arrests and patients without a history of pre-injury arrests, (2) patients classified as substance abusers and non-abusers, and (3) patients with and without a history of pre-injury illicit drug use on the basis of demographic characteristics, injury characteristics, and neurobehavioural functioning. Results indicate significant differences between patients with a history of pre injury arrests and patients without a history of pre-injury arrests in terms of demographic and injury characteristics. Differences were also noted between persons classified as substance abusers and non-abusers in terms of demographic and injury characteristics, and neurobehavioural functioning. Clinical implications and future research are discussed. PMID- 11201316 TI - Are neuropsychiatric symptoms associated with evidence of right brain injury in referrals to a neuropsychiatric brain injury unit? AB - Studies suggest that neuropsychiatric symptoms are more common in patients with injury to the right side of the brain. However, most studies have examined patients with penetrating injuries because these allow more accurate localization of brain damage. This study investigates whether a similar association would be found in patients with non-penetrating brain injuries presenting to a neuropsychiatric unit. Over a 2 year period, 98 referrals were examined. Damage was localized using routine operation notes, EEG and neuroimaging. In total, 34 patients (35%) had a predominately right-sided injury, 33 (34%) had a left-sided injury and 31 (32%) had a diffuse or bilateral injury. Right-sided injuries were associated with hallucinations (p = 0.05), and left-sided injuries were associated with confabulation (p = 0.05) and lack of insight (p = 0.07). These results are consistent with findings from patients with penetrating head injuries. They suggest that evidence of the laterality of injury may be useful for planning the rehabilitation of patients seen in neuropsychiatric brain injury units. PMID- 11201317 TI - Attentional deficits in patients with post-concussion symptoms: a componential perspective. AB - Attentional deficits are frequently reported by patients suffering from closed head injuries. The majority will develop a group of clinical symptoms known as post-concussion symptoms or syndromes (PCS), which are characterized by a range of subjectively experienced symptoms including headaches, dizziness, fatigue, irritability, slowed thinking, and memory dysfunction. It is posited that attentional deficit is the crucial factor for the apparent failures of memory and higher cognitive functioning, and may contribute largely to difficulty in re integrating back into the community and resuming independent daily living. It also appears that there are large variations within these patients, in terms of both presented symptoms and neuropsychological performances. However, these variations in terms of attentional deficits have not been systematically differentiated and examined. This article aims to build up a theoretical framework to guide the investigation of the varieties of attentional deficits in patients with PCS. Current theories on attention from cognitive psychology, neuropsychology, cognitive neuroscience and clinical rehabilitation will be reviewed and integrated. It is hoped that a better understanding of the underlying mechanism of such defects will foster and guide the development of intervention. PMID- 11201318 TI - Universal neonatal hearing screening--parental attitudes and concern. AB - This study addresses parental attitudes and concern in relation to universal neonatal hearing screening by otoacoustic emissions (OAE) testing. The parents of 87 children who had participated during the first year of the universal neonatal hearing screening programme at University Hospital, Linkoping, Sweden were included in the study. These children were all tested during this period and later cared for at three well-baby clinics (part of their primary healthcare). A questionnaire was given to the parents during routine medical check-ups at the well-baby clinics when the infants were 5-6 months of age. Ninety-five per cent of parents stated that they had a positive attitude towards neonatal hearing screening, 1% were ambivalent and 4% were negative about it. The parents wanted early detection of hearing loss and the possibility of early intervention. It was also found that screening did not disturb the children. A few parents were anxious due to repeated testing of their children. The information provided in connection with the test was found to be sufficient by 77% of parents, whereas 11% of parents had negative comments about it (e.g. they wanted more information about the otoacoustic emissions technique). The general attitude among parents towards universal neonatal hearing screening was very positive in that they felt reassured by it. The risk of disturbing the parent-child relationship by early screening seems to be small, and could be further minimized by improved information and rapid and effective follow-up. PMID- 11201319 TI - Evidence on the efficacy of insert earphone and sound field VRA with young infants. AB - Visual reinforcement audiometry (VRA) with insert-earphone stimulus delivery provides a means of obtaining early ear-specific information on the auditory status of infants. The aim of this study was to investigate the efficacy of VRA in young infants, and to compare the use of sound field and insert-earphone stimulus presentation. VRA was performed on 41 normally developing infants aged between 20 and 42 weeks. Infants were tested in the sound field (n=22) and with insert earphones (n=19). Results showed significantly more minimum response levels (MRLs) obtained with sound field testing, and with older children. Nevertheless, in the insert-earphone group, 36% of those aged 32 weeks or more gave two or more MRLs, and 25% of the infants aged 25 weeks or less gave one or more MRLs. This study provides data from developmentally normal infants which confirms the efficacy of insert-earphones as well as sound field VRA with 32-42 week-olds, with reasonable expectation of success. The data in this study also suggest that VRA could be usefully employed for younger infants aged approximately 20-26 weeks where information, although less easily obtained, may be of particular value to early diagnosis and habilitation. PMID- 11201320 TI - Children's experience of tinnitus: a preliminary survey of children presenting to a psychology department. AB - Tinnitus has been much researched within adult populations with consideration of prevalence as well as the impact of tinnitus on individual's lives. Although the literature highlights the prevalence of tinnitus in children, there is little information on its effects from a psychological perspective. This small-scale preliminary study looked at 24 children (50% with normal hearing and 50% with a hearing loss) who presented to the Psychology Department with troublesome tinnitus. In line with adult studies, preliminary results suggested that tinnitus can have as marked an effect on children's lives as it is reported to have on adults. Insomnia, emotional distress, listening and attention difficulties are the main psychological factors associated with tinnitus in children. These, in turn, may have an effect upon their school performance. Differences were found between children with normal hearing and those with some degree of hearing loss. Overall, children with normal hearing found tinnitus more troublesome and presented with higher levels of anxiety than those with some level of hearing impairment. The present study suggests that children who complain of tinnitus should be taken seriously. In terms of management, individual intervention packages were found to be useful in alleviating anxiety and other associated factors. Recommendations are made on areas for future research. PMID- 11201321 TI - Measurement of the temporal-modulation transfer function for a single listener with cochlear hearing loss and left-hemisphere damage. AB - The modulation depth required for the detection of sinusoidal amplitude modulation applied to a white noise carrier was measured as a function of modulation frequency, giving temporal modulation transfer functions (TMTFs). Five adult listeners with normal hearing (mean age 52 years), five elderly listeners with moderate cochlear hearing loss (mean age 66 years) and a single elderly listener (aged 73 years) with moderate cochlear hearing loss and left-hemisphere damage were tested in the right ear at 50 dB SL. The five elderly listeners were matched in audiogram with the brain-damaged listener. Modulation detection was systematically poorer than normal in the five elderly listeners with cochlear hearing loss. However, their TMTFs were lowpass in shape, as for the five normal hearing adult listeners. Modulation detection was much poorer in the elderly listener with cochlear hearing loss and left-hemisphere damage compared to the five normal-hearing adults and the five elderly listeners with cochlear hearing loss. Moreover, modulation detection was poorer at 4, 64 and 128 Hz than at 8, 16 and 32 Hz in the brain-damaged listener, giving his TMTF a bandpass appearance. These results are in agreement with the hypothesis that the main factors limiting the ability to detect changes in the temporal-envelope of sounds are located at a central (retro-cochlear) level of the auditory system rather than at a peripheral (cochlear) level. They also suggest that the TMTF approach may prove useful in distinguishing peripheral and central hearing losses. PMID- 11201322 TI - Speech perception with steeply sloping hearing loss: effects of frequency transposition. AB - Six adults with a very steeply sloping high-frequency hearing loss listened to monosyllabic words in several conditions. In the first condition, their ability to identify phonemes with a signal-to-noise ratio of 6 dB was measured. Results were similar to those of normally hearing subjects listening to the same material through low-pass filters having comparable cut-off frequencies. In the remaining two conditions, four of the hearing-impaired subjects, and a control group of five normally hearing subjects, listened to speech in quiet with and without frequency transposition. The transposition lowered all speech frequencies by a factor of 0.6. Specific auditory training with transposed speech materials different from the materials used in the tests of speech perception was provided in 10 sessions, each of one hour's duration, which were scheduled at weekly intervals. Despite this training, no significant differences were found between the two conditions in these subjects' recognition of words. It is concluded that such a frequency-transposition scheme, if implemented in a wearable hearing aid, would be unlikely to benefit people with a sloping hearing impairment of this type. PMID- 11201323 TI - Age-related changes in the visual perception of phonologically significant contrasts. AB - The purpose of the present study was to determine whether the ability to speechread phonological contrasts is influenced by age. Forty-eight subjects were equally represented in three age groups: 8-9 years, 11-12 years and adults (20-29 years). The Hebrew version of the Speech Pattern Contrast (HeSPAC) test was administered by speechreading alone. Results showed that: age influenced performance; performance was contrast-dependent (place contrasts highly visible, manner and vowel height partially visible and voicing contrast invisible); hierarchy of contrast performance was similar for all age groups; Hebrew and English differ in the visual accessibility to speech contrasts in final voicing only; and females were found to be poorer speechreaders than males for the partially visible contrasts. The results suggest that speechreading at the phonological level follows a developmental course. The implications of these findings extend to recommendations provided to children in noisy listening conditions, speechreading training in hearing-impaired children and those with central auditory processing disorders (CAPD), and to the design of sensory aids. PMID- 11201324 TI - Insertion gain measurements using two low-powered analogue hearing aids. AB - Differences between insertion gain measurements and coupler measurements were investigated using two different hearing aids, to assess the accuracy of hearing aid fitting methods which involve the use of real-ear-to-coupler differences (RECDs). The hearing aids used were the NHS BE19 and the Lavis X11. They were allocated alternately to 80 new adult hearing aid users, and insertion gain measurement was carried out with the allocated aid on all subjects, and with both hearing aids on 36 subjects. Coupler measurements were also carried out with both hearing aids, at two different gain settings. Comparison of the coupler measurements and the insertion gain measurements suggests that the differences in insertion gain produced by different hearing aids cannot be predicted accurately from the differences in coupler gain measurements produced by the same aids. Although the use of RECDs measured using insert earphones may accurately predict the real-ear performance of some models of hearing aid, this method may not produce equally satisfactory results with other models. PMID- 11201325 TI - Acoustic characteristics of reconstructed ear canal after atresia surgery. AB - The acoustic properties of the reconstructed ear canals of 13 patients after atresia surgery were investigated by comparing them with those of contralateral healthy ear canals. In the third post-operative month, resonant frequency, amplitude and bandwith of the ear canals with Q-factor were measured. Probe microphone measurements showed a significant shift in resonant frequency in the direction of the higher frequencies, and a non-significant change in bandwith in the atresia surgery group. The suggested reason may be a change in ear canal curvature, altered vibration pattern and sound-absorption characteristics of the skin graft lining the reconstructed ear canal. PMID- 11201326 TI - Population genetics of Lithuanians. AB - The primary objective of this article was to overview the present-day knowledge on genetic features of the Lithuanian population. Genetic differentiation within the Lithuanian population and the relationship between Lithuanians and other European populations was analysed by means of blood groups, serum protein polymorphisms and DNA markers including mtDNA. The results of the research have shown small differences between present-day Lithuanian ethnolinguistic groups, which probably go back to the prehistoric Baltic tribal structure. The Baltic peoples show a mixture of eastern and western genetic traits, e.g. a high frequency of the blood group B combined with a very high frequency of the Rh negative blood group. Studies of the Baltic 'tribal gene' LWb indicate the presence of a considerable Baltic admixture in the neighbouring Finno-Ugric and Slavic populations. PMID- 11201327 TI - Month of birth and height of Spanish middle-aged men. AB - We examined whether body height differs in Spain, a country having a high number of hours of sunlight, between middle-aged males and females born during the months with the longest and those born in the months with the shortest periods of daylight hours. We used data from a cross-sectional survey that documented standardized measurements of height and other variables for a 2021-person random multi-stage sample representative of the Spanish population aged 35-64 years. The relationship between height and month of birth was analysed by multiple linear regression, adjusting for age, occupation and type of residence. Male adults born in summer proved to be 1.7 cm taller than their counterparts born in winter (95% confidence interval 0.2-3.3 cm, p = 0.03). This relationship was most marked for those whose occupation was non-manual (2.1 cm, p = 0.04 vs 1.4cm, p = 0.2 in manual occupations). No significant (p = 0.8) or relevant (0.16 cm) summer- and winter-related differences in height were found in women. These results are compatible with the hypothesis that adult male height could be partially influenced by physical environmental factors such as the action of sunlight during the early stages of life. PMID- 11201328 TI - Age at natural menopause in Beirut, Lebanon: the role of reproductive and lifestyle factors. AB - PRIMARY OBJECTIVE: To determine the median age of natural menopause and factors associated with the timing of menopause in Beirut, Lebanon. RESEARCH DESGIN: A population-based sample of 298 women were interviewed using a semi-structured questionnaire. METHODS AND PROCEDURES: Logit analysis and logistic regression were used to estimate the median age and identify correlates of menopausal status. MAIN OUTCOMES AND RESULTS: The median age of natural menopause in Beirut, Lebanon is estimated to be 49.3 years. Not being currently married (odds ratio (OR)=4.19, 95% CI: 1.53, 11.51) and smoking (OR = 1.02 for each year of smoking, 95% CI: 1.00, 1.05) are significantly associated with an earlier age at menopause. Women with menstrual bleeding longer than 5 days have later ages at menopause (OR = 0.50, 95% CI: 0.26, 0.97). Age at menarche, parity, education and socio-economic status are not statistically associated with the age at menopause. CONCLUSIONS: The age at natural menopause in Lebanon is comparable to median ages reported for women in industrialized countries (49.3-51.4). Our results emphasize the role of smoking in determining an earlier age at menopause and indicate that reproductive characteristics affect the timing of menopause. PMID- 11201329 TI - An assessment of biological age of males in Poland. AB - BACKGROUND: Studies carried out in Poland have shown that some important indices of growth and maturation in children, of the biological well-being during adulthood and the rates of premature mortality depend strongly upon the individual's position on the social scale. AIM: The study considers whether adult males of higher educational status differ from their chronological age-matches of lower educational status in biological age. SUBJECTS AND METHODS: The data of 2800 occupationally active men, aged 25-65 from the 1994/1995 Polish Health Surveys were used. Twenty-two different measures were used. Biological age was assessed by the method of Borkan and Norris (Journal of Gerontology, 35, 177-184, 1980). RESULTS: A comparison of biological age profiles of two groups of males based on their educational status showed that in 13 of the 22 characteristics. better-educated men were biologically younger than their poorer educated peers (p < 0.05). CONCLUSION: Better education is associated with the slowing down of the process of ageing, probably because it produces a healthier life-style. PMID- 11201330 TI - Daily rat tibial growth in vivo following hypothalamic sex reversal with neonatal and pubertal treatments with gonadal steroids. AB - A striking sex-related difference in postpubertal growth and growth hormone (GH) secretory pattern in the rat has been described. Although this sexual dimorphism seems to be determined by the neonatal effects of gonadal steroids on the hypothalamus, peripubertal exposure to steroids also plays an important role. In order to study the real influence of the hypothalamic sex and/or peripubertal gonadal steroids, the growth pattern of female and male rats in response to neonatal and peripubertal sexual steroid treatments was studied using microknemometry, a technique that allows non-invasive daily measurements of rat tibial growth rate. Neonatal steroid environment in males was modified by castration on day 1, whereas in females it was changed by a single neonatal testosterone administration on day 5 followed by castration at 13 days of age. From the onset of puberty to adulthood, both female and male animals received testosterone or estrogens, respectively. Neonatal treatment alone, i.e. androgenization of female and castration of male rats, were only able to induce a partial reversal of the original sex-dependent growth pattern. Additional peripubertal treatments achieved a complete change in the sex-linked growth pattern. Consistent with the effects observed on growth, the pituitary GH concentration was significantly increased in females, and diminished in males, when they were treated both at the neonatal and peripubertal stages. However, only this latter group, whose growth was more seriously compromised, showed decreased plasma insulin-like growth factor-I (IGF-I) levels. In conclusion, a complete feminization of male tibial growth pattern or masculinization of female pattern can only be achieved by maintaining the new steroid environment from puberty to adulthood. PMID- 11201331 TI - Longitudinal growth of Bangladeshi infants during the first year of life. AB - The growth in length and weight of 91 poor urban Bangladeshi infants was monitored at monthly intervals from birth to 1 year. At birth 18%, 22% and 8% were below -2.00 standard deviations of the National Center for Health Statistics (NCHS) height-for-age, weight-for-age and weight-for-height, respectively and at 1 year the percentages were 40%, 40% and 7%. Infant weights over the first 6 months associated positively with both mother's BMI and percentage body fat. Higher mean infant weights from 6 to 12 months were associated with both higher educational status of the mother and monthly family income and the latter two variables provided the best model for predicting weight velocity from birth to 12 months. Internal Z-scores, corrected for day of measurement, provided clear evidence of catch-up/catch-down over the first 6 months with heavier and longer babies at birth showing catch-down while lighter and shorter babies demonstrated catch-up. Infants' weights were almost three times more variable than lengths. Monthly incremental variability of both infant weight and length increased sharply from 6 to 12 months with weight showing significantly more variability. The correlations of birth weight and length with subsequent distances and monthly increment revealed that the first 6 months were dominated by catch-up and catch down but during the latter half of the year the growth phenomena were influenced mainly by earlier intra-uterine or genetic effects. PMID- 11201332 TI - Age at menarche: secular trends and association with adult anthropometric measures. AB - BACKGROUND: Age at menarche has been used as a marker of environmental conditions during childhood. Previous work has shown trends of decreasing age at menarche throughout the 19th century, but reported trends in the 20th century have been less consistent. The nature of the relationship between age at menarche and adult life anthropometric measures may be important in understanding the importance of this measure on disease in later life. AIM: To establish whether mean age at menarche changed during the first half of the 20th century, and to determine the nature of associations between age at menarche and anthropometric measures in young adulthood. SUBJECTS AND METHODS: 3433 female students, who were born between 1919 and 1952 and who attended health checks at the student health service of the University of Glasgow between 1948 and 1968. RESULTS: Mean age at menarche decreased from 13.2 years in the earliest born to 12.5 years in the latest born students. These results were not explained by changes in socio demographic factors. Menarcheal age was positively associated with height and negatively associated with weight and BMI, results independent of socio demographic and behavioural factors. CONCLUSIONS: The falling age at menarche described here may be related to nutritional influences in the first half of the 20th century. The influence of menarche on BMI in early adulthood may have important health consequences. PMID- 11201333 TI - Habitual physical activity of Senegalese adolescent girls under different working conditions, as assessed by a questionnaire and movement registration. AB - OBJECTIVE: The aim of this study was to measure habitual physical activity in a group of Sereer adolescent females from Senegal. The hypothesis tested was that physical activity levels of adolescent Senegalese girls differ according to location and living conditions and may have a negative impact on growth and nutritional status. DESIGN: Studies of physical activity within the framework of a longitudinal study of growth during puberty. METHODS: All the adolescents were born and had been raised in the same rural communities, but some worked as maids in the cities during the dry season (migrants) while the others remained in the villages all year round in order to help their families in daily domestic and agricultural tasks (non-migrants). The study was undertaken in both rural and urban settings on a subsample of 40 migrant and 40 non-migrant girls aged 13.4 15.3, drawn from a cohort of 406 adolescents followed up since 1995. Nutritional status was estimated from anthropometric measurements; sexual maturation was based on stage of breast development and occurrence of menarche. Intensity and patterns of physical activity were derived from movement registration by accelerometry for a 3-day period. The nature and frequency of daily tasks were evaluated by questionnaires. RESULTS: As a whole, the adolescents studied here were smaller, thinner and less mature than girls of the same age from developed countries. Migrants weighed 3.5 kg more than nonmigrants and had more muscularity and a thicker fat subcutaneous layer. The day-to-day reliability of accelerometry counts was excellent (intraclass correlation coefficient: 0.90. 95% CI: 0.85 0.93). Mean daily (24 h) physical activity counts were higher for migrants than for non-migrants. Migrants spent more time engaged in moderate to heavy activity than did non-migrants (9.3 h/24 h versus 6.1 h/24 h). Non-migrants slept or were inactive for a longer period than migrants (7.6h/24h versus 6.3 h/24h). They also rested for a longer period of the day (2.1 h/24 h versus 0.8 h/24 h). When examining the influence of maturational status on physical activity, there was a clear difference between the two groups: the less mature migrants were more active, whereas the reverse was true in villages, where girls at the end of puberty reached higher intensity indices. CONCLUSIONS AND IMPLICATIONS: In both situations, the activity level was high. The nutritional status of migrants was better despite a heavier work load. Differences could be explained by better living conditions and food intake in cities. PMID- 11201334 TI - Spray-dried microspheres containing ketoprofen formulated into capsules and tablets. AB - In this study, microspheres were prepared by a spray-drying technique using solutions of ketoprofen and two polymers, cellulose acetate butyrate (CAB) and hydroypropylmethylcellulose phthalate (HPMCP), in different weight ratios. Different total concentrations were used in the feed solutions: 3, 6 and 9% w/v. The spray-dried microparticles were characterized in terms of shape (SEM), size (light scattering method), production yield and encapsulation efficiency. They were formulated into capsules; tablets were prepared by direct compression of the microparticles mixed with maltose and, in some cases, hydroypropylmethylcellulose (HPMC). In vitro release studies were performed both at acidic and neutral pHs. The spray-drying process of solutions of ketoprofen with polymeric blends of cellulose derivatives leads to microparticles which, depending on their final formulation (capsules or tablets), can give a rapid or prolonged drug release. The formulations here described can be proposed for the oral administration of NSAIDs. PMID- 11201335 TI - Literature alerts. PMID- 11201336 TI - Preparation of microcapsules containing rare-earth metal elements. AB - Microcapsules for internal radiation therapies containing the rare-earth metal elements Dy, Ho and Cu with a diameter of 5-10 microm were successfully obtained by an interfacial polymerization method and a successive sedimentation technique was employed to fractionate the microcapsules. A triisocyanate monomer and tricresylphosphate were used for a wall forming material and a core solvent for the metals, respectively. The amount of the metal elements loaded was measured using a high frequency plasma photoemission apparatus. The beta-ray radioactivity of 1 mg of microcapsules irradiated with a common neutron source is estimated as 370 microCi, which is satisfactorily strong for usual radiotherapy, when microcapsules containing Dy are used. Differential interference microscopy indicated narrow size distribution of the fractionated microcapulses. PMID- 11201337 TI - Improvement of encapsulation efficiency of water-in-oil-in-water emulsion with hypertonic inner aqueous phase. AB - Water-in-oil-in-water (w/o/w) emulsions encapsulating tryptophan or theophylline were prepared where these compounds are regarded as model drugs. The effects of sodium chloride on the drug entrapment into the w/o/w emulsions and on the separation of aqueous phases were studied. The degree of encapsulation of tryptophan in the w/o/w emulsion increased with the concentration of sodium chloride added in the inner aqueous phase, while it decreased with that in the outer aqueous phase. As for theophylline, although the degree increased with a concentration of sodium chloride in the inner phase, the effect was smaller than that on tryptophan. The difference in the effects between on tryptophan and on theophylline was attributed to their partition coefficients. Theophylline was easily leaked out from the inner phase to the outer aqueous phase after its dissolution and diffusion in the oil phase due to a higher partition coefficient. More than 55% of the aqueous phase was separated from the w/o/w emulsion within 24 h, when sodium chloride was not added in the inner aqueous phase. However, the separation was not observed when more than 0.2M sodium chloride was added. To the contrary, sodium chloride added in the outer aqueous phase accelerated the separation. It was, therefore, concluded that sodium chloride in the inner aqueous phase plays an important role in suppression of the separation and in encapsulation of the drug which does not penetrate into the oil membrane. PMID- 11201338 TI - Photocatalytic activity of TiO2 particulate films prepared by depositing TiO2 particles with various sizes. AB - TiO2 particles of various sizes were prepared by grinding in cyclohexanone, and TiO2 particulate films were obtained by depositing these TiO2 particles with various sizes onto a glass or quartz substrate. The effect of the particle size and thickness on the photocatalytic properties of the films was evaluated via oxidative degradation of gaseous 2-propanol. The initial rate of 2-propanol degradation under UV light irradiation for the films deposited with 30 nm TiO2 particles increased with increasing film thickness up to 600 nm, and reached a saturated value above this film thickness. Photocatalytic activity for the films with thickness below 600nm was larger when smaller TiO2 particles were deposited onto the substrate, due to the increase in the surface area of the particulate films. Furthermore, saturated values of the photocatalytic activity for thick films were smaller for the films deposited with smaller particles, which is mainly attributed to the change in crystal form of the particles during the grinding treatment. PMID- 11201339 TI - Mucoadhesive chitosan-coated liposomes: characteristics and stability. AB - Lecithin liposomes, empty or containing FITC-dextran, were prepared by the ethanol injection method. Three different types of chitosans with different molecular weight and degrees of deacetylation were used (Seacure 113, 210 and 311). Chitosan coating was carried out by mixing the liposomal suspension with the chitosan solution followed by incubation. The size of liposomes was measured before and after polymer coating by an image analysis technique. The mean diameter of liposomes containing FITC-dextran was in the size range 250-280 nm, whereas the size after coating was 300-330 nm, regardless of chitosan type. All chitosan-coated liposomes were of spherical shape and no morphological differences between uncoated and coated liposomes were observed. Liposomes with FITC-dextran, originally entrapping 50% of the marker substance taken in the preparation and coated in the presence of unentrapped marker substance, contained 60-65% of the marker substance. The highest entrapment was found for liposomes coated with medium molecular weight chitosan. The stability of chitosan-coated liposomes in simulated gastric fluid was significantly higher as compared to uncoated liposomes. One can conclude that chitosan is stabilizing the original liposomal structure and protecting liposomally entrapped drug. PMID- 11201340 TI - Preparation of PEG-grafted immunomagnetoliposomes entrapping citrate stabilized magnetite particles and their application in CD34+ cell sorting. AB - Immunomagnetic systems have been used for positive selection of a cell fraction from a mixture using appropriate surface markers with satisfactory results, as haematopoietic CD34+ cells. This work reports on the development of poly(ethylene glycol)-grafted (PEG) immunoliposomes loaded with citrate-magnetite stabilized particles as the separation vehicles for immunomagnetic separations. The magnetic ferrofluid was encapsulated into PEG-liposomes by the DRV methodology. The magnetoliposomes had a liposomal size of approximately 450 nm and a Fe/lipid molar ratio of 1.52+/-0.26, and were retained in the magnetic field created by the MiniMACS system. Anti-CD34 immunomagnetoliposomes with 100 mAb/vesicle were prepared by coupling the My10 mAb and bound specifically for CD34+ KG-1a cells in culture and in mixtures with CD34-cells (CHO or Jurkat). The magnetic cell sorting was carried out in cell mixtures KG-1a/CHO or KG-1a/Jurkat with different initial% of CD34+ Kg-1a cells. For 10(6) positive cells and 100 microM of immunomagnetoliposomes, the capture efficiency was > 85% and independent of the starting percentage of CD34+ cells. The decrease of the final purity, when the starting percentage of CD34+ cells decreases and, dependent of the CD34- cell line used, point to the degree of non-specific cell binding of My10 immunomagnetoliposomes as being crucial, among of the methodological aspects as the number of starting CD34+ cells. The CD34+ cells isolated retained the viability with an estimated recovery of 45-50%. PMID- 11201341 TI - Long-acting delivery microspheres of levo-norgestrol-poly(3-hydroxybutyrate): their preparation, characterization and contraceptive tests on mice. AB - The preparative technology for sustained release drug delivery microspheres of levo-norgestrol-poly(3-hydroxybutyrate) was optimized based on the in-liquid drying method. The formation of the drug microspheres was confirmed with differential thermal analysis. The appearance, particle size and distribution, residual CHCl3, drug content, drug release characteristics in vitro, stability and anticonceptive effect on mice of the microspheres were all examined. The average particle size was 64 microm with over 90% of the microspheres being in the range of 28.7-85.8 microm. The residual CHCl3 was lower than 0.001%. The drug release behaviour in vitro could be described by the Higuchi equation and the drug release t1/2 was prolonged by 1.8 times, compared with the original drug LNG. The microspheres were stable for 3 months and showed significant sustained release and anticonceptive effect in mice, and lower toxicity compared with the original drug. PMID- 11201342 TI - Effect of adding non-volatile oil as a core material for the floating microspheres prepared by emulsion solvent diffusion method. AB - Eudragit microspheres, to float in the gastrointestinal tract, were prepared to prolong a gastrointestinal transit time. To enhance their buoyancy, non-volatile oil was added to the dispersed phase. When an oil component was not miscible with water, over 90% was entrapped within the microspheres and prolonged the floating time of the microspheres. Depending on the solvent ratio, the morphologies of the microspheres were different and the best result was obtained when the ratio of dichloromethane:ethanol:isopropanol was 5:6:4. As the isopropanol portion increased, the time to form microspheres was delayed and the amount of fibre-like substance produced was decreased, due to the slow diffusion rate of the solvent. Compared with microspheres prepared without non-volatile oil, the release rate of the drug from microspheres was faster in all cases tested, except the microspheres containing mineral oil. The solubility of the drug in the non volatile oil affected the release profiles of the drugs. The non-volatile oil tends to decrease the glass transition temperature of prepared microspheres and change the release profile. The internal morphology of the microspheres was slightly different depending on the entrapped oil phase used. Tiny spherical objects were present at the inner surface of microspheres and the inside of the shell. PMID- 11201343 TI - Fatty acid substituted polyvinyl alcohol as a supporting material for microsphere preparation. AB - Polyvinyl alcohol, substituted with lauric, myristic, palmitic, and stearic acids at different substitution degrees was employed for the preparation of biodegradable microspheres containing progesterone or indomethacin. A solvent extraction/method was followed, starting from an oil-in-water dispersion containing the polymer and drug in the inner phase. Microspheres were obtained with high loading efficiency, whose release properties were dependent on the nature of the acyl substituent and the substitution degree. Kinetics approaching zero-order were obtained for the most hydrophile microspheres such as those based on the least substituted polymers and lowest molecular weight substituents. The hydrophilicity of these systems hindered protein absorption on their surface, suggesting their suitability for parenteral use. PMID- 11201344 TI - Controlled release of vancomycin from biodegradable microcapsules. AB - Poly D,L-lactic acid (PLA) and its copolymers with glycolide PLGA 90:10 and 70:30 were polymerized under various conditions to yield polymers in the molecular weight range 12000-40000 daltons, as determined by gel permeation chromatography. Vancomycin hydrochloride was the hydrophilic drug of choice for the treatment of methicillin resistant Staphyloccoccal infections. It was microencapsulated in the synthesized polymers using water-oil-water (w/o/w) double emulsion and solvent evaporation. The influence of microcapsule preparation medium on product properties was investigated. An increase in polymer-to-drug ratio from 1:1 to 3:1 caused an increase in the encapsulation efficiency (i.e. from 44-97% with PLGA). An increase in the emulsifier (PVA) molecular weight from 14-72 kD caused an increase in encapsulation efficiency and microcapsule size. The in vitro release of vancomycin from microcapsules in phosphate buffer saline (pH 7.4) was found to be dependent on molecular weight and copolymer type. The kinetic behaviour was controlled by both diffusion and degradation. Sterilization with 60Co (2.5 Mrad) also affected the degradation rate and release profiles. Degradation of microcapsules could be seen by scanning electron microscopy, by the increase in the release rate from PLA and by the decrease in the Tg values of microcapsules. In vitro bactericidal effects of the microcapsule formulations on S. aureus were determined with a special diffusion cell after the preparations had been sterilized, and were found to have bactericidal effects lasting for 4 days. PMID- 11201345 TI - The utilization of health care services and social services by neurotic patients and their service need. PMID- 11201346 TI - The performance of the Center for Epidemiologic Study Depression Scale (CES-D) in an Arab female community. AB - BACKGROUND: The purpose of this study was to investigate the psychometric properties of the Arabic version of the CES-D. METHODS: Three samples of young Arab females were chosen from different young female populations (n =450). The translated version of the CES-D, sociodemographic and risk factors questionnaires were applied to the above three samples. A subsample was selected (n = 30) to re rate the scale items and the same sample was interviewed by the SCID. The internal consistency and test-re-test reliability were estimated as well as the factor structure of the Arabic CES-D. The discriminative and criterion validity of the scale was also investigated using the ROC analysis. RESULTS: Seventy five percent (n = 350) of the subjects completed the scale. Alpha coefficient was found to be 0.88 and the split-half reliability was 0.83. The average re-test reliability (ICC = 0.59). Factor analysis yielded three factors: interpersonal problems, mixed affective/somatic factor and the positive affect factor. There was significant differences in mean total score between depressed and non depressed subjects as classified by SCID as well as by self-perception of depression and the need for treatment. ROC analysis revealed that a cut-off point of 21 discriminated best between depressed and non-depressed subjects (sensitivity= 82%, specificity = 83% with AUC of 84%). CONCLUSION: The Arabic CES D was found to possess reasonable reliability and reasonable discriminative and criterion validity. PMID- 11201347 TI - Mental health care in Italy: organisational structure, routine clinical activity and costs of a community psychiatric service in Lombardy region. AB - The Magenta Community Mental Health Centre (CMHC) is the public agency responsible for providing adult psychiatric care to about 85,000 adult residents. In 1995, it had 1,145 clients and incurred costs of Euro 1.9 millions. Average cost per patient and per adult resident were Euro 1,661 and Euro 22.2, respectively. These values mask large variation across diagnosis: while patients with schizophrenia and related disorders had an average cost of Euro 3,771, those with neurotic and related disorders had an average cost of Euro 439. Patients with schizophrenia and related disorders (28% of the patients) absorbed about 60% of total costs and made extensive use of several types of services (hospital, outpatient, domiciliary, social and rehabilitative care). Since integrating different types of services is the key element of Italian psychiatric care, the new fee-for-service system adopted by the NHS to fund providers does not appear appropriate, particularly for schizophrenic patients. PMID- 11201348 TI - Child mental health problems in Arab children: application of the strengths and difficulties questionnaire. AB - AIM: This study aimed at establishing the mental health profile among 322 Arab children living in the Gaza strip. METHOD: Children were selected in four age bands, i.e. 3, 6, 11 and 16 years of age. The relevant forms of the Strengths and Difficulties Questionnaire (SDQ) was completed by parents, teachers and 16-year olds. RESULTS: Factor analyses of the parent-related questionnaires identified similar general factors as in the UK-based studies of validating the SDQ. Certain items did not load as highly on the general factors, i.e. distractability, feeling scared, feeling unhappy, stealing, and being picked or bullied. Emotional problems items were rated differently in the pre-school group (aches, nervousness clinging, worries) than in previous studies. Using previous optimal cut-off scores, parent SDQs revealed higher rates of children with emotional and conduct problems falling above the 90th centile established in the UK sample, but lower rates according to self-report SDQs by 16-year-olds. CONCLUSIONS: Western categories of mental health problems did not clearly emerge from the factor analysis. The main difference from western epidemiological studies appeared to operate in parents' perceptions of emotional problems in pre-school children. The SDQ is very promising as a screening measure or rating scale in different cultural populations. However, future research should identify and establish indigenously meaningful constructs within this population and culture, and subsequently revise measures of child mental health problems. PMID- 11201349 TI - Help-seeking pathways among Malay psychiatric patients. AB - The aim of this study is to explore the help-seeking behaviour of Malay psychiatric patients. A semi-structured interview based on a standard proforma was conducted to assess help seeking process and delays for Malay psychiatric patients attending the psychiatric clinic for the first time. Help-seeking process and delays were defined. Among 134 patients evaluated in the study, 69% had visited traditional healers (bomoh) for the present illness before consulting psychiatrists. The second popular choice of treatment was medical practitioner and only a small percentage of them had consulted homeopathic practitioners and herbalists. Patients who had consulted bomohs were significantly delayed in getting psychiatric treatment compared with those who had not consulted them. Consultation of bomohs was significantly higher among married patients, those with major psychiatric illnesses and in family who believed in supernatural causes of mental illness. However, there was no significant difference in age, gender, educational status and occupation between patients who had consulted and not consulted bomoh. We concluded that majority of the Malay psychiatric patients had sought the traditional treatment prior to psychiatric consultation. The strength of social support and the belief of the patients, friends, and/or relatives in supernatural causes of mental illness were strongly associated with the rate of traditional treatment. Deep-seated cultural beliefs were major barrier to psychiatric treatment. PMID- 11201350 TI - The effects of psychotherapies: a study on patients' perception of results in an Italian public setting. AB - Enquiries centred on the perspective of users of psychiatric treatments and their families, has become an increasingly widespread method to improve the quality of treatments administered by health services. In this study, in particular, we examine the users' perception of the quality and variability of the effects of psychotherapies, the difficulties met, and the perceived help factors. The sample consists of 216 users of psychotherapy and 223 patients in psychiatric treatment with psychological support. They are outpatients, managed by the public health service. The questionnaires included closed ended, open-ended questions and scales that were previously tested on a sample of patients. The questionnaire for patients was anonymous and administered by researchers external to the medical staff. Irrespective of the diagnosis or of a concurrent pharmacological therapy, a high percentage of patients (75%), in both groups, feel improved. Improvement consist of the decrease of symptoms, a sense of feeling better, but also feeling grown up, more mature, having higher self-esteem and feeling more adequate in interpersonal relationships. This last type of result is significantly more frequent in the group of patients in psychotherapy. Besides these patients are faced with more difficulties and play more active a role while they are in treatment. The main difference between patients in psychotherapy and those in psychiatric management with psychological support is not indeed the identification of different perceived therapeutic factors, but rather the different evaluation of their relative importance. On the whole, the study seems to show that the effects of real psychotherapies include, beside an improvement of symptoms, the achievement of goals of personal growth and maturity, self satisfaction and an increase in self-esteem, all in accordance with a conception of health as well-being and self-satisfaction rather than as absence of illness. PMID- 11201351 TI - Predictors of post-hospital employment status for psychiatric patients in Hong Kong: from perceptions of rehabilitation professionals to empirical evidence. AB - Fifty participants with mental illness and a concrete discharge plan were selected from two mental hospitals in Hong Kong and assessed on their Psychosocial support by the Chinese Version of the Significant Others Scale, social vocational competence using the Workshop Behavior Checklist and the Vocational Social Skills Scale, medical history, work history, and demographic variables. At three months after discharge, the employed participants (n = 12) were shown to have better psychosocial support and social vocational competence than the unemployed participants (n = 24) by univariate comparison. The employed and unemployed participants did not differ in their medical and work history, and demographic variables. Implications of the results for rehabilitation programming are discussed. PMID- 11201352 TI - Survival and plant-prey finding by Neoseiulus fallacis (Acari: Phytoseiidae) on soil substrates after aerial dispersal. AB - In a greenhouse and in an open field, aspects of aerial and ambulatory dispersal of the phytoseiid mite. Neoseiulus fallacis (Garman) were studied with a focus on events that would occur after aerially dispersing mites had landed on soil or associated substrates. We measured recovery of predators on lima bean plants (Phaseolus lunatus L.) that were infested with the two-spotted spider mite, Tetranychus urticae Koch. Factors thought to affect movement and colonization were distance to a receiver unit from a release (landing) point, intervening soil surfaces such as clods, gravel, fine soil and grass, and management of soil surfaces such as mulching. watering or both. In the field, the effect of distance (0.11-1.76 m) from a landing point to a receiver unit was significant, with a negative log-linear relationship. Soil surfaces such as clods and management actions such as watering with mulching allowed for more capture of predators on bean plants with prey than did other treatments. Environmental conditions greatly affected survival of N. fallacis. Predators in the field that were present on bare soil suffered high mortality (ca. 90%) at fluctuating daytime conditions of 26.4 +/- 4.8 degrees C and 56 +/- 13.4% RH. Predators only suffered 10% mortality in the greenhouse under the same setting, but under more controlled and favorable environmental conditions. Effects of environmental conditions, mode of dispersal and implications to biological control are discussed. PMID- 11201353 TI - Life cycle and parasitic interaction of the lizard-parasitizing mite Ophionyssus galloticolus (Acari: Gamasida: Macronyssidae), with remarks about the evolutionary consequences of parasitism in mites. AB - Wild-caught specimens of the lacertid lizard Gallotia galloti eisentrauti from the Canary Island of Tenerife were checked for ectoparasites. The parasitic gamasid mite Ophionyssus galloticolus Fain and Bannert (2000) was very abundant on these lizards. Additionally, parasitism by larvae of two species of Trombiculidae (Prostigmata: Parasitengona) was observed. O. galloticolus was reared in the laboratory on its natural host in order to investigate its life cycle, reproductive biology, and development. The life history of O. galloticolus is documented in detail and compared to literature data of other Ophionyssus species. O. galloticolus was found to be similar to other species of the same genus with respect to the duration of development, the precopulatory association of protonymphs, and the arrhenotokous development of eggs. However, it seems to be more tolerant towards low relative humidity and longer starvation periods than other Ophionyssus species. Evolutionary transformations of the life-history pattern of this genus and other parasitic mites in comparison to its predatory precursors involve a reduction or partial suppression of ontogenetic instars in order to decrease mortality during host-seeking phases, and a compensating increase in growth capacity of the remaining feeding instars facilitated by replacement of sclerites through elastic cuticle or by growth of new cuticle unrelated to a moult (neosomy). PMID- 11201354 TI - Detection and micro-scale isolation of a low molecular mass paralysis toxin from the tick, Argas (Persicargas) walkerae. AB - This study describes the isolation of a 11 kDa paralysis toxin from crude larval extracts of Argas (Persicargas) walkerae by exploiting the cross-reactivity of a monoclonal antibody (4B12), directed against the paralysis toxin of Rhipicephalus evertsi evertsi. This low molecular mass is in contrast to previous findings of a 60-70 kDa toxin for A. (P.) walkerae, but is similar to neurotoxins isolated from venomous forms of the class Arachnida, which comprise the orders Araneae (spiders). Scorpionida (Scorpions) and Acari (ticks and mites). Since numerous antigenic bands, ranging between 11 and 115 kDa, were detected by the monoclonal antibody 4B12, the possibility of toxin-complex formation and the effect of pH on the latter were investigated by means of HPLC and ammonium sulphate precipitation. The results suggest that physiological conditions, with respect to pH and ionic strength, promote the formation of heterogeneous toxin-complexes while an acidic pH favours the formation of a more homogeneous toxin-containing complex. Furthermore, the effect of partially purified toxin on neurotransmitter release from crude rat brain synaptosomes was investigated, since tick paralysis toxins are hypothesised to inhibit neurotransmitter release from the presynaptic terminal. Both calcium-dependent, as well as calcium-independent release was inhibited by the toxin-containing sample. PMID- 11201355 TI - Host utilization and seasonal occurrence of Dermacentor species (Acari:Ixodidae) in Missouri, USA. AB - A total of 3,235 Dermacentor variabilis (Say) specimens were collected from birds, mammals, and by dragging vegetation, and 2,683 D. albipictus (Packard) ticks were collected from deer from 1993 to 1996. Peak seasonal occurrence of adult D. variabilis was from May through July with a precipitous decrease in August. Nymphal D. variabilis populations peaked in June. Peak activity of larvae was bimodal, with one activity peak during late summer (September) and a second peak in winter or early spring. The raccoon, Procyon lotor (L.), was the principal host of adults followed by the Virginia opossum, Didelphis virginiana Kerr. Rodents and the eastern cottontail rabbit, Sylvilagus floridanus (J. A. Allen), were the primary hosts of nymphs. The marsh rice rat, Oryzomys palustris (Harlan), was the principal host of larvae followed by the pine vole, Microtus pinetorum (Le Conte), and white-footed mouse, Peromyscus leucopus (Rafinesque). All stages of D. albipictus were found only on white-tailed deer, Odocoileus virginianus (Zimmermann). Numbers of adult and nymphal D. albipictus peaked in November, whereas larvae peaked in September. PMID- 11201356 TI - Immunization of cross-bred cattle against Hyalomma anatolicum anatolicum by purified antigens. AB - Extracts prepared from unfed larvae of Hyalomma anatolicum anatolicum were purified by immunoaffinity chromatography using anti-gut IgG as ligand. Affinity purified antigen (Aff-GHLAg) was used to immunize cross-bred (Bos taurus x B. indicus) calves of 6-7 months of age. Immunized calves rejected 70.6% larvae, 54.5% nymphs and 61.9% adults. No significant changes in the engorged weight of females was observed; however, significant decrease in the engorgement weight of larvae and nymphs was recorded. There was a significant decrease in the emerging nymphs (p < 0.05) and adults (p < 0.01) of the tick stages fed on immunized animals. SDS-PAGE analysis revealed three antigenic proteins of 100, 59.4 and 37 kDa responsible for induction of resistance in the host. PMID- 11201357 TI - Experimental infestation of llamas (Lama glama) with Boophilus microplus (Acari:Ixodidae). AB - Two llamas (Lama glama) were infested with approximately 20,000 Boophilus microplus larvae each and maintained under controlled conditions to collect the detached adult ticks. A total of 72 engorged and semi-engorged females were recovered with a mean weight of 163.0 +/- 70.6 mg. Sixty-three (87.5%) of these ticks oviposited and 60 (95.2%) of the egg masses produced larvae. Six of the heaviest females laid 18,838 eggs from which 16,545 (87.8%) hatched. These results show that llamas are able to maintain a population of B. microplus under experimental conditions. Further studies are required to determine the role of llamas as alternative hosts for B. microplus under field conditions. PMID- 11201359 TI - Attachment sites and frequency distribution of erythraeid mites, Leptus indianensis (Acari: Prostigmata), ectoparasitic on harvestmen, Leiobunum formosum (Opiliones). AB - Host attachment sites and frequency distribution of parasitism were investigated for the larval erythraeid mite Leptus indianensis parasitising a sample of 500 harvestmen. Leiobunum formosum in Tennessee, USA. A significant difference was found in the number of mites attached to different body segments of the harvestmen with the greatest number of mites attached to femurs I-IV. Scanning electron microscopy revealed that the mites attached to smooth areas of the host integument between rows of stout setae. The frequency distribution of mites parasitising the harvestman population was highly clumped (Coefficient of Dispersion = 3.34) with a relatively small number of hosts being parasitised by most of the mites. PMID- 11201360 TI - The effect of male ticks on the feeding performance of immature stages of Rhipicephalus sanguineus and Amblyomma americanum (Acari: Ixodidae). AB - A unique group of immunoglobulin-binding proteins (IGBPs), produced by ixodid male ticks during the latter half of their prolonged feeding period, improves the feeding performance of co-feeding females. As a follow-up to this observation, we investigated whether male tick feeding also affects the feeding of other developmental stages. Immature stages of Rhipicephalus sanguineus (Latreeille) and Amblyomma americanum (L.) were fed on rabbits in the presence or absence of conspecific males. The mean weight of larvae and nymphs of both species that fed around males and detached from the host on the first day of dropping was significantly higher than when the immature ticks fed on rabbits in the absence of males. However, larvae of both species and nymphs of R. sanguineus that fed slower and detached on the second day of dropping did not show significant differences in weight. A similar pattern was observed for A. americanum nymphs although, unlike R. sanguineus, the presence of males also influenced the feeding performance of the nymphs that fed slowly and detached on the second day of drop off. The improved feeding performance demonstrated by immature ticks in the presence of males may be due to immunomodulatory saliva proteins, such as immunoglobulin-binding proteins (IGBPs) that are introduced into the co-feeding site. The results are considered in relation to the distribution of ixodid tick species on their natural hosts. PMID- 11201358 TI - Diseases of mites. AB - An overview is given of studies on diseases of mites. Knowledge of diseases of mites is still fragmentary but in recent years more attention has been paid to acaropathogens, often because of the economic importance of many mite species. Most research on mite pathogens concerns studies on fungal pathogens of eriophyoids and spider mites especially. These fungi often play an important role in the regulation of natural mite populations and are sometimes able to decimate populations of phytophagous mites. Studies are being conducted to develop some of these fungi as commercial acaricides. Virus diseases are known in only a few mites, namely, the citrus red mite and the European red mite. In both cases, non occluded viruses play an important role in the regulation of mite populations in citrus and peach orchards, respectively, but application of these viruses as biological control agents does not seem feasible. A putative iridovirus has been observed in association with Varroa mites in moribund honeybee colonies. The virus is probably also pathogenic for honeybees and may be transmitted to them through this parasitic mite. Few bacteria have been reported as pathogens of the Acari but in recent years research has been concentrated on intracellular organisms such as Wolbachia that may cause distorted sex ratios in offspring and incompatibility between populations. The role of these organisms in natural populations of spider mites is in particular discussed. The effect of Bacillus thuringiensis on mites is also treated in this review, although its mode of action in arthropods is mainly due to the presence of toxins and it is, therefore, not considered to be a pathogen in the true sense of the word. Microsporidia have been observed in several mite species especially in oribatid mites, although other groups of mites may also be affected. In recent years, Microsporidia infections in Phytoseiidae have received considerable attention, as they are often found in mass rearings of beneficial arthropods. They affect the efficacy of these predators as biological control agent of insect and mite pests. Microsporidia do not seem to have potential for biological control of mites. PMID- 11201361 TI - Declining trends in HTLV-I prevalence among blood donors in Japan. PMID- 11201362 TI - Decline in the positive rate of human T-lymphotropic virus type-1 (HTLV-1) antibodies among blood donors in Nagasaki. AB - OBJECTIVE: The aim of this study was to clarify the trend of the HTLV-1 seroprevalence rate among blood donors. METHODS: Samples were screened by the particle agglutination test for HTLV-1 antibodies. MATERIALS: Serum from blood donors was screened. RESULTS: The positive rate of HTLV-1 antibodies among blood donors decreased from 13.14 to 0.81 % over the years from 1928 to 1983. CONCLUSION: A decline over the years in the positive rate of HTLV-1 antibodies among blood donors was revealed. PMID- 11201363 TI - Esophageal inflammatory pseudotumor mimicking malignancy. AB - A 54-year-old man with a complaint of dysphagia was found to have a prominent stricture in the proximal esophagus. A biopsy of the stenotic area indicated sarcoma, leading to subtotal esophagectomy. The surgically removed esophagus demonstrated a well-defined intramural mass, consisting of a mixture of fibroblastic cells with bland cytological appearances and inflammatory cells. Reflux esophagitis which was present distal to the stricture seemed to play a role in the development of this inflammatory pseudotumor. PMID- 11201364 TI - Ultrasonography of gastric volvulus: "peanut sign". AB - We report a case of chronic gastric volvulus in which ultrasonography (US) was useful. An 81-year-old woman was hospitalized due to vomiting, and upper gastroduodenoscopy revealed that the stomach was spirally twisted and constricted. An upper gastrointestinal barium study demonstrated an organoaxial mesenteroaxial combined type gastric volvulus. US showed constriction between the dilated upper stomach body and the lower stomach body similar to a "peanut". Thereafter, the patient's vomiting stopped and follow-up US demonstrated that the constriction of the stomach was loosened. Therefore, we believe that this characteristic US sign paralleled the symptoms of the patient. PMID- 11201366 TI - Vascular involvement in Behcet's disease. PMID- 11201365 TI - Poorly vascularized malignant insulinoma displaced the pancreatic ducts around the mass on endoscopic retrograde cholangiopancreatography. AB - A 66-year-old woman with an altered mental status caused by hypoglycemia was referred to Akita City Hospital. Abdominal ultrasonography (US) and endoscopic US revealed an isoechoic mass measuring 25 mm in the head of the pancreas. Endoscopic retrograde cholangiopancreatography (ERCP) revealed that the main pancreatic duct and its branches were displaced around the mass in the head of the pancreas. On arteriography, a poorly vascularized tumor was observed. Dynamic contrast-enhanced computed tomography (CT) showed a low-attenuation mass in the head of the pancreas. A pylorus-preserving pancreaticoduodenectomy was performed. Microscopically, the diagnosis was malignant insulinoma. PMID- 11201367 TI - A Japanese case of congenital hyperinsulinism with hyperammonemia due to a mutation in glutamate dehydrogenase (GLUD1) gene. AB - We describe a Japanese case of neonatal hyperinsulinism due to a de novo mutation (Gly446Asp) in glutamate dehydrogenase gene (GLUD1). A boy suffered from hypoglycemic coma with relative hyperinsulinemia on day 1 after birth, and received subtotal pancreatectomy. Examination of the resected pancreas revealed a diffuse increase in endocrine cells, consistent with 'nesidioblastosis'. He is now 15 years old and has exhibited mild but persistent hyperammonemia, which is a very unique feature of the disorder caused by GLUD1 activating mutations. He has also been suffering from seizures and mental retardation. Thus, GLUD1 mutations can be a cause of congenital hyperinsulinism in Japanese. PMID- 11201368 TI - Duodenal somatostatinoma and erythrocytosis in a patient with von Hippel-Lindau disease type 2A. AB - A female with von Hippel-Lindau (VHL) disease type 2A first presented with erythrocytosis at the age of 9 years. This patient revealed multiple paragangliomas at age 22. After the removal of tumors, a retinal hemangioblastoma developed. Our diagnosis of VHL disease type 2A was confirmed. Moreover, systemic examination showed a duodenal somatostatinoma. Frequent and long-term monitoring is important for patients with pheochromocytomas or paragangliomas, and a screening for VHL disease and other hereditary cancer syndromes is recommended. Recognition of neuroendocrine tumors as a manifestation of VHL disease permits earlier diagnosis and improves prognosis. PMID- 11201369 TI - Basedow's disease and chronic ulcerative colitis: a case report and review of the Japanese literature. AB - A case of Basedow's disease, that developed after successful treatment of ulcerative colitis with a total colectomy, is presented, along with a review of the Japanese literature on the coexistence of hyperthyroidism and ulcerative colitis. A 26-year-old man was referred to our department, complaining of general fatigue, appetite loss, and palpitation. At age 14, blood was discovered in his stool and a diagnosis of ulcerative colitis was made. Since then, he has been treated with salazosulfapyridine and prednisolone. On examination, mild exophthalmos and thyroid swelling were observed. Both serum free T3 and T4 levels were increased along with a positive TSH receptor antibody, while TSH was decreased. Scintigraphic and ultrasonographic examinations of the thyroid gland showed diffuse enlargement. Treatment with thiamazole relieved the symptoms and normalized the thyroid function. Although a high incidence of autoimmune thyroid diseases in association with ulcerative colitis has been suggested, only 6 cases of hyperthyroidism coexisting with ulcerative colitis have been reported in Japan. A common immunological process has been suggested to be implicated in the pathogenesis of this association, however, the exact mechanism remains unclear. PMID- 11201370 TI - Usefulness of the combination of pre- and intraoperative selective intraarterial calcium injection to detect residual insulinomas. AB - In a 35-year-old woman diagnosed with insulinoma selective intraarterial calcium injection was positive for proximal gastroduodenal artery and inferior pancreaticoduodenal artery involvement preoperatively. Although non-invasive imaging studies were negative, a mass was detected at the pancreatic uncus by intraoperative ultrasonography. Gastroduodenal artery calcium injection was performed after enucleation of the tumor. Following calcium injection, the insulin level was inappropriately increased and further pancreaticoduodenectomy was performed. After excision, another tumor was detected at the head of the pancreas by histopathological examination. As shown, selective intraarterial calcium injection is useful to localize tumors preoperatively and intraoperatively. PMID- 11201371 TI - Clinical features of fulminant hepatitis in Nagasaki Prefecture, Japan. AB - OBJECTIVE: Fulminant hepatitis is a rare but fatal disease. In the present study, we examined the changes in etiology and prognosis of fulminant hepatitis in Nagasaki Prefecture, Japan between 1980 to 1999. METHODS: Eighty-one patients with fulminant hepatitis admitted to our hospitals from 1980 to 1999 were examined with respect to the etiology and prognosis. RESULTS: Fulminant hepatitis was due to hepatitis A virus in 2 (12%) cases, hepatitis B virus in 18 (22%) cases, unknown etiology in 50 (62%) cases, and drug-induced in 11(14%) cases. The number of cases in the first half of the study (1980-1989) was 47 and that of the latter half (1990-1999) was 34 cases. The incidence of fulminant hepatitis type B also decreased from 14 cases (30%) to 4 cases (12%) during these periods. The overall survival rate of fulminant hepatitis was 32%; it was equal in fulminant hepatitis type B, fulminant hepatitis of unknown etiology and fulminant drug induced hepatitis. The survival rate of fulminant hepatitis type A was 100%, though only two cases were identified. Retrospectively, the survival rate in patients with a pre-encephalopathy period of < or = 10 days and aged < or = 39 years was significantly higher than in patients > or = 40 years of age (p<0.01). There was no difference between the two age groups when pre-encephalopathy period was > or = 11 days. CONCLUSIONS: The incidence of fulminant hepatitis especially that of fulminant hepatitis type B in Nagasaki Prefecture has decreased in recent years. The survival rate is significantly higher in younger patients with a short pre-encephalopathy period. PMID- 11201372 TI - IgA nephropathy with complement deficiency. AB - We treated a female patient suffering from immunoglobulin A (IgA) nephropathy and congenital deficiency of the ninth component of the complement system (C9). She was admitted with hematuria and proteinuria, and the C9 deficiency was diagnosed based on the low hemolytic activity of 50 % of the hemolytic unit of the complements (CH50) and the normal C3 level in the plasma. Renal biopsy revealed mild mesangial proliferation, and immunofluorescence examination revealed mild mesangial deposits of IgA and C3 with the same distribution. We discuss the pathogenesis of IgA nephropathy and the role of the complements in its progression. PMID- 11201373 TI - A solitary bronchial papilloma with malignant changes. AB - We describe a case of solitary papilloma of the bronchus and provide a review of 38 similar cases reported in Japan. A 70-year-old man complained of cough and sputum. Chest X-rays and CT scans revealed atelectasis of the right middle lobe. On bronchoscopy, a polypoid tumor was found at the orifice of the bronchus of the right middle lobe. The tumor was histologically diagnosed as a squamous papilloma with moderate atypia. Because of elevated tumor markers and the reported high incidence of malignant changes in papillomas, the tumor was endoscopically resected by electrosurgical snare. While this procedure resulted in improvement of atelectasis, the chest CT taken subsequently revealed a mass adjacent to the resected polypoid tumor in the middle lobe bronchus. Percutaneous needle biopsy followed by histopathological examination confirmed the tumor to be a squamous cell carcinoma. Only three cases of malignant changes in papillomas have been previously reported in Japan. Electrosurgical snare, which allows the identification of tissue at the tumor base, should be the treatment of choice rather than YAG laser surgery. PMID- 11201374 TI - Two cases of severe bronchopneumonia due to influenza A (H3N2) virus: detection of influenza virus gene using reverse transcription polymerase chain reaction. AB - We report two cases of severe bronchopneumonia due to influenza A (H3N2) virus. The severity of the disease necessitated initiation of empiric therapy based on the present illness and clinical data on admission. Both patients were improved by artificial ventilation with positive end-expiratory pressures and administration of broad spectrum antibiotics and corticosteroids before confirming the diagnosis of viral bronchopneumonia using viral culture and serological tests. Within 24 hours, influenza A (H3N2) virus was identified by amplification of the pathogen genes by reverse transcription polymerase chain reaction (RT-PCR) using the stored bronchoalveolar lavage (BAL) fluids of both cases. This suggests that a combination of detection methods of pathogens using RT-PCR and BAL fluid will facilitate determination of rational treatment aimed at influenza A virus. PMID- 11201375 TI - Cardiac and great vessel thrombosis in Behcet's disease. AB - Behcet's disease (BD) is a chronic relapsing systemic vasculitis in which orogenital ulceration is a prominent feature. The disease affects many systems and causes hypercoagulability. We present a 27-year-old male patient who exhibited widespread great vessel thrombosis including right atrial and ventricular thrombi in the setting of right-sided infectious endocarditis and orogenital aphthous ulcerations and erythema nodosum due to BD. We reviewed the enigmatic prothrombotic state of BD, and discuss our prior experiences in this field. PMID- 11201376 TI - Acute congestive heart failure associated with a limited form of systemic sclerosis and primary biliary cirrhosis. AB - This is the first case of a limited form of systemic sclerosis (ISSc) associated with acute congestive heart failure (CHF) and primary biliary cirrhosis (PBC). A 58-year-old woman with ISSc was admitted because of a sudden onset of CHF. The intravenous administration of nitroglycerine and furosemide ameliorated the symptoms of CHF within 24 hours. She had both anticentromere antibodies and anti p25 doublet/triplet antibodies to intrahepatic microsomes. Thallium scintigraphy at rest demonstrated significant perfusion defects in both the anteroseptal and inferior myocardium. A coronary angiogram revealed normal coronary arteries and no vasospasm was provoked by the intracoronary administration of acetylcholine. The present case indicates that minute care should thus be taken for the prevention of acute CHF even in patients with a limited form of SSc when thallium perfusion defects are identified. PMID- 11201377 TI - Device for the removal of button batteries. AB - OBJECTIVE: There is an increasing number of accidents by erroneous ingestion of button batteries in recent years; the batteries arouse the interest of infants because of their attractive shape and luster. The batteries remaining in the gastrointestinal tract and discharging electric current over a long period of time may induce ulceration or perforation, thus must be carefully considered the selection of appropriate treatment. METHODS: We remove erroneously ingested button batteries with two tubes with ferrite magnets nearly the same size as the button batteries themselves. PATIENTS: Four cases of erroneous ingestion of button batteries. RESULTS: We easily removed button batteries from the stomach within 5 minutes in all cases with two magnet-attached tubes. CONCLUSION: We present this battery removal device together with a literature review, because it seems convenient and useful. PMID- 11201378 TI - [Refractory non-small-cell lung cancer responding to combination chemotherapy with docetaxel, gemcitabine and cisplatin]. AB - The combination of docetaxel (TXT), gemcitabine (GEM), and cisplatin (CDDP) produced a regression in a squamous cell carcinoma of the lung that had recurred after radiation therapy plus chemotherapy, and was resistant to the combination of carboplatin (CBDCA) with etoposide (ETP) or paclitaxel (TXL). The patient was a 62-year-old man with squamous cell lung cancer, which was first successfully treated by a combination of radiation therapy and chemotherapy, but showed local recurrence after 8 months. Although the recurrence was treated with CBDCA plus ETP and then TXL, the tumor continued to grow with symptomatic progression of airway stenosis. The tumor began to regress after the regimen of TXT, GEM and CDDP was started. This therapy achieved PR with symptomatic improvement. The combination of TXT, GEM and CDDP may be effective for recurrent non-small-cell lung carcinoma, even in patients that have failed to respond to more than one chemotherapy regimen. PMID- 11201379 TI - [Usefulness of ambulatory adjuvant chemotherapy with low-dose epirubicin in patients with axially-node positive breast cancer: Chiba Epirubicin Cooperative Study Group]. AB - We evaluated the usefulness of adjuvant chemotherapy with low-dose epirubicin (EPI) as a key drug in patients with axially-node positive breast cancer. All the 24 patients who were entered in the study between January 1991 and December 1992 were shown histologically to have more than 4 axially-node involvement and underwent curable resection for the breast lesions. Twenty mg/m2 of EPI was administered intravenously every 4 weeks as ambulatory treatment for 1 year and 5 fluorouracil (5-FU) and tamoxifen (TAM) were concomitantly administered at a dose of 150 mg/day and 20-40 mg/day, respectively, daily for 2 years. The median follow-up period was 70 months with a 55.1% 5-year relapse-free survival and 67.4% 5-year survival rate. One patient developed Grade 3 nausea.vomiting, anorexia and general fatigue; however, the other toxicities were mild, such as Grade 1 leukopenia, liver dysfunction, nausea.vomiting, anorexia and general fatigue. This adjuvant therapy with low-dose EPI was safely administered to outpatients, and is considered to be useful for the treatment of axially-node positive breast cancer. PMID- 11201380 TI - [Induction of apoptosis in breast cancer cells by preoperative oral administration of 5-fluorouracil]. AB - We investigated whether 5-fluorouracil (5-FU) can induce apoptosis in breast cancer cells. Preoperatively, 23 breast cancer patients were divided into a group treated with 5-FU at 200 mg/day for 2 weeks (Group A) and a non-treatment group (Group B), and breast cancer tissues were taken postoperatively. DNA fragmentation by agarose electrophoresis and the TUNEL method were used to investigate the induction of apoptosis. The labeling rate with Ki-67 was measured to study the reproductive activity of tumor cells. The involvement of p53 in the apoptosis decision mechanism was also studied. DNA was more fragmented in Group A than in Group B. The apoptosis index by the TUNEL method was 1.88 +/- 1.03 in Group A, which was significantly higher than 0.36 +/- 0.86 in Group B. The labeling rate with Ki-67 was significantly higher in Group B(62.3 +/- 21.7) than in Group A (29.8 +/- 16.0). There was no difference in the protein expression of p53 regardless of the presence or absence of DNA fragmentation. These results indicate that 5-FU administration induces apoptosis in breast cancer cells and significantly inhibits their reproductive activity. Involvement of p53 in the apoptosis decision mechanism was not demonstrated. PMID- 11201381 TI - [Patient compliance and the quality of life are well maintained in weekly paclitaxel and carboplatin therapy for advanced gynecologic cancers in Japanese women]. AB - OBJECTIVES: To assess patient compliance and efficacy of a combination chemotherapy consisting of weekly administration of paclitaxel and carboplatin for gynecologic malignancy in Japanese women. METHODS: Fourteen ovarian and three uterine cancer patients received 80 mg/m2 of paclitaxel (paclitaxel) and AUC 1.5 to 2.0 of carboplatin weekly. The toxicity was evaluated and patients' QOL was tested. RESULTS: Neutropenia higher than grade 3 were observed in 29.4%. Four patients received G-CSF support. Grade 1 neurotoxicity was seen in 76.5% of patients. Evaluation of QOL by EORTC-QLQC30 showed significantly better tolerance of a weekly than monthly regimen. Three out of four patients with lung metastasis showed complete disappearance of the lesions. One patient with stage IIIb cervical cancer underwent postchemotherapy-hysterectomy and a complete pathological response was confirmed. The overall response rate was 64.7% including patients previously treated with platinum based multidrug regimens. CONCLUSIONS: A weekly paclitaxel and carboplatin regimen was well tolerated by Japanese women. The regimen was active in over 60% of cases and it also appeared active in multidrug resistant cases. PMID- 11201382 TI - [Theoretical construction of chemotherapeutic tactics for advanced or recurrent gastrointestinal carcinoma]. AB - The anti-cancer effect of 5-fluorouracil (5-FU) is significantly affected by the intratumoral environment. Elevated expression of thymidylate synthase (TS), the target enzyme of 5-FU, and a lack of reduced folate or FdUMP results in insufficient inhibition of TS. Further, elevated expression of DPD in the tumor tissue results in a lack of FdUMP. TS-1, which contains tegafur and dihydroxypyridine (CDHP), a potent DPD inhibitor, is a promising anticancer drug. Isovorin has been available in Japan since autumn 1999. In cancer patients, folate deficiency may be derived from increased consumption and/or absorption disturbance of folate. In such situations, sufficient TS inhibition cannot be obtained if 5-FU is administered without supplementation of reduced folate. We describe in detail the metabolism of those substances in relation to the anticancer effect of 5-FU. Further, we show the theoretical construction of first line and second-line chemotherapy with consideration of TS and DPD expression. PMID- 11201383 TI - [Efficacy of lidocaine cream in protecting against thermal stress during hyperthermia]. AB - Hyperthermia is performed in combination with chemotherapy as multimodal treatment for recurrent and advanced cancer. It is generally believed that the temperature cannot be raised higher because of thermal stress. In this study, we examined the efficacy of lidocaine cream in protecting against thermal stress during hyperthermia. We devised a new local anesthetic cream containing 5% lidocaine. The subjects were eighteen patients with stomach cancer, liver cancer, or large intestine cancer. This cream was applied locally to the skin with an occlusive dressing for about one hour before hyperthermia was performed, and was wiped away just before hyperthermia. The pain scores in the treatment group were significantly lower than in the no-treatment group (p < 0.05). The scores for sensation of heat in the treatment group were lower, though not to a significant extent, than those in the no-treatment group. No adverse effects were observed. Plasma concentrations of lidocaine were lower than 0.5 microgram/ml, and percutaneous absorption of lidocaine from the lidocaine cream was minimal. PMID- 11201384 TI - [Recurrent breast cancer successfully treated with a weekly dose of paclitaxel--a case report]. AB - The patient was a 46-year-old women who was treated for axillary lymph node recurrence of breast cancer by a variety of methods, including surgery, chemotherapy, and radiotherapy, but who experienced recurrences in the cervical and mediastinal lymph nodes and skin, and developed hydrothorax and ascites. Although the recurrent foci responded to 4 cycles of CAF chemotherapy, there was concern that the foci would become refractory or resistant to chemotherapy. The administration of paclitaxel was therefore initiated. The patient received a dose of paclitaxel once a week for 5 consecutive weeks followed by a 1-week recovery period (one cycle). After two cycles of the paclitaxel treatment, a marked shrinkage of the lymph nodes and complete resolution of the hydrothorax and ascites were observed. Even though the patient exhibited bone marrow suppression and G-CSF was administered twice for neutropenia, there were no adverse effects except mild alopecia, again suggesting the possibility that paclitaxel is effective chemotherapy for recurrent breast cancer. PMID- 11201385 TI - [A case of advanced gastric cancer with Virchow's and paraaortic lymph node metastases successfully resected after combined chemotherapy of low-dose CDDP and 5-FU]. AB - The patient was a 61-year-old woman who had Stage IV advanced gastric cancer with Virchow's and paraaortic lymph node metastases. The lesions were considered surgically incurable, so she was placed on neoadjuvant chemotherapy consisting of low-dose CDDP and 5-FU. After 3 courses of chemotherapy, the tumor had decreased remarkably in size and Virchow's metastasis had disappeared. She was considered to have a partial response (PR) and underwent distal gastrectomy. Histopathological examination of the primary tumor revealed that almost all cancer cells existed in the mucosal and submucosal layers; few had infiltrated the serosa. A few paraaortic lymph nodes were positive for metastasis, but a curative resection (Cur B) was performed. The patient received another course of chemotherapy after the operation. Low-dose CDDP and 5-FU therapy was associated with few adverse events in this case, and thought to be effective against advanced gastric cancer. PMID- 11201386 TI - [Effectiveness of high-dose, intermittent 5'-DFUR therapy for advanced gastric cancer]. AB - We report a case of advanced gastric cancer with multiple liver metastases and peritoneal dissemination. The patient was effectively treated with high-dose 5' DFUR. A 52-year-old patient with advanced gastric cancer and multiple liver metastases, who showed a high serum level of CEA and CA19-9 underwent simple D1 gastrectomy. Thereafter, he received per os 1,200 mg/day of 5'-DFUR intermittently (5 days a week) and TAI every four months postoperatively. The serum levels of both CEA and CA19-9 fell dramatically to within the normal range and were maintained thereafter until the present. The size and number of the liver metastases dramatically decreased, judging from CT and angiography findings. PMID- 11201387 TI - [A case of stage IV gastric cancer with multiple liver metastases and carcinomatous ascites responding to TS-1 for six months before progression]. AB - We report the case of a 72-year-old male with Stage IV gastric cancer accompanied by multiple liver metastases and carcinomatous ascites which responded to chemotherapy using TS-1. Treatment of the patient with daily oral administration of 120 mg TS-1 for 4 weeks resulted in complete regression of the liver metastases and ascites, as well as a 35% reduction in the size of the primary lesion. After 2 cycles, the primary tumor size was reduced to 55% and serum CA19 9 and CA125 levels were decreased to the normal ranges. This regimen was effective without any adverse effects, and improved the patient's QOL, for 6 months before progression of liver lesions. The patient received chemotherapy at our outpatient clinic for 10 months after the first treatment, after which he died of peritonitis carcinomatosa. The current case suggests that TS-1 may have a potent therapeutic efficacy in advanced gastric cancer patients. PMID- 11201388 TI - [Survival of 2 years and 7 months with 5'-DFUR treatment in a patient with peritoneal gastric cancer recurrence]. AB - A 79-year-old male patient with peritoneal recurrence of gastric cancer 1 year and 7 months after radical operation was treated by oral administration of 5' DFUR. After the beginning of oral administration of 5'-DFUR, he survived 2 years and 7 months with a good performance status and without any adverse effects. A very limited number of cases with long survival by the oral administration of 5' DFUR after peritoneal recurrence of gastric cancer have been reported. Of a total of 653.0 g of 5'-DFUR administrated, 436.8 g (66.9%) were given in a protocol consisting of daily oral 1,600 mg of 5'-DFUR for 7 consecutive days and 7 drug free days. This high-dose (1,053 mg/m2/day) and intermittent method of 5'-DFUR administration might have contributed to the long survival and good performance status of this patient. PMID- 11201389 TI - [A patient with obstructive jaundice due to recurrence after gastric cancer surgery responding remarkably to FLP combination therapy]. AB - The patient was a 67-year-old man who had undergone distal gastrectomy because of early gastric cancer without lymph node metastasis two years earlier. The postoperative course was uneventful, but he was admitted again to our hospital because of abrupt jaundice. A CT scan of the abdomen showed obstructive jaundice due to the enlargement of the lymph nodes around the hepatoduodenal ligament, pancreas head, portal vein, and celiac axis. After percutaneous transhepatic cholangio-drainage (PTCD), 5 cycles of FLP combination therapy (5-fluorouracil, leucovorin, cisplatin) were performed. Consequently, the tumor marker level returned to the normal range and the shrinkage of the metastatic lymph nodes was remarkable. A reopening of the biliary tract was attained, so the PTCD tube could be removed. As an outpatient without recurrence he has received oral administration of uracil plus tegafur. The FLP combination therapy was effective for obstructive jaundice due to intraperitoneal lymph node recurrence of the gastric cancer. PMID- 11201390 TI - [Long survival in a case of unresectable hepatic metastasis from rectal carcinoma treated with second-look hepatectomy plus pharmacokinetic modulating chemotherapy (PMC)]. AB - A 67-year-old female with rectal cancer and multiple liver metastases underwent low anterior resection by total mesorectal excision (TME), cholecystectomy and hepatic arterial cannulation in June 1995. She was treated with hepatic arterial infusion chemotherapy (HAI) (5-FU 600 mg/m2/day x 2 days/w) and oral UFT (400 mg/body, 5 days/w) once a week for 6 months on an outpatient basis. As the metastatic foci of the liver significantly decreased (83.3%) and extrahepatic disease were not observed, partial resection of the liver (second-look hepatectomy) was performed in March 1996. She continued arterial infusion PMC and venous infusion PMC as an outpatient. During the follow-up period a lung metastasis appeared in November 1997. Her regimen was changed to modified PMC with MMC (mitomycin C) and CPT-11. She has been managed at our outpatient clinic while the lung metastasis remained but with no liver metastasis for 57 months after the first operation, until the present. Second-look hepatectomy and PMC with a two-way port system was a useful option for unresectable hepatic metastases from colorectal carcinoma. PMID- 11201391 TI - Modification of lung cancer prevention by gene-nutrient interaction. PMID- 11201392 TI - Cancer incidence among workers in six Norwegian aluminum plants. AB - OBJECTIVES: This study investigated associations between exposure to polycyclic aromatic hydrocarbons (PAH) and the incidence of lung, bladder, kidney, and pancreatic cancer among Norwegian aluminum plant workers. METHODS: Cancer incidence was investigated from 1953 to 1996 among 11,103 men employed for more than 3 years in the industry, giving 272,554 person-years during follow-up. A job exposure matrix was constructed to estimate exposure to particulate PAH and fluorides. The observed cases of cancer were compared with expected figures calculated from national rates. Dose-response relations were investigated by internal comparisons using Poisson regression and stratified analyses for standardized incidence ratio. Potential confounding by smoking was investigated in subanalyses restricted to 3 of the plants. RESULTS: The study showed an overall excess for bladder cancer, standardized incidence ratio 1.3 (95% confidence interval 1.1-1.5), which increased with increasing cumulative exposure to PAH and reached a relative risk of about 2 for the upper exposure category in the analysis with 30 years of lag time. There was no association between cumulative PAH exposure and lung cancer, but there were indications of an elevated risk of kidney cancer among the most heavily PAH-exposed persons in the analyses with a lag time of 30 years. For pancreatic cancer we found a higher incidence among the PAH-exposed persons than among the unexposed ones, but no clear dose-response association was found. CONCLUSIONS: The study showed an association between bladder cancer and exposure to PAH, but gave no support to an association between PAH exposure and lung cancer in the primary aluminum industry. PMID- 11201393 TI - Nonmalignant mortality among workers in six Norwegian aluminum plants. AB - OBJECTIVES: This study investigated the associations between exposure to fluorides and polycyclic aromatic hydrocarbons (PAH) and mortality from nonmalignant diseases among workers in the Norwegian primary aluminum industry. METHODS: Mortality among 10,857 men, employed for more than 3 years in 1 of 6 aluminum plants, was investigated from 1962 to 1996, giving 239,246 person-years during follow-up. Ajob-exposure matrix covering all 6 plants was used to estimate the individual exposure to total fluorides and particulate PAH. The observed cause-specific deaths were compared with expected figures calculated from national rates. Dose-response relations were investigated by internal comparisons using Poisson regression and by stratified analyses for standardized mortality ratio. Potential confounding by smoking was investigated in subanalyses restricted to 3 of the plants for which information on smoking habits was accessible. RESULTS: Mortality from circulatory disease was slightly lower than expected [SMR 0.95, 95% confidence interval (95%CI) 0.9-1.0], while there was an increased mortality from asthma, emphysema, and chronic bronchitis combined, SMR 1.2 (95% CI 1.0-1.5). Mortality from these diseases was associated with cumulative exposure to fluorides. The rate ratio in the internal analysis rose steadily to 2.5 (95% CI 1.5-4.3) for the upper exposure category. No association was observed between cumulative fluoride exposure or PAH exposure and circulatory mortality. CONCLUSIONS: The study showed an association between exposure to potroom emissions measured by fluorides and mortality from asthma, emphysema, and chronic bronchitis combined. PMID- 11201394 TI - Bladder cancer in the textile industry. AB - OBJECTIVES: This study examined the occupations and industries at high risk for bladder cancer in an area where the textile industry is plentiful and the incidence of the disease is very high. METHODS: A case-referent study concerning 218 incident bladder cancer cases diagnosed during 1993-1995 in the county of Valles Occidental, Barcelona, was carried out. A reference group (N=344) was selected from municipal lists matched to the cases by age, gender, and area of residence. All the subjects were personally interviewed, and a complete occupational history was abstracted together with other sociodemographic and life style factors. All odds ratios (OR) and 95% confidence intervals (95% CI) were adjusted for age, gender, and smoking. RESULTS: No overall excess risk was found forever having worked in the textile industry (OR 1.13, 95% CI 0.79-1.63) nor for specific sectors of this industry (ie cotton, wool, silk). An excess risk was observed for spinners and winders employed for more than 20 years (OR 3.28, 95% CI 1.08-9.97) and for machine setters employed between 1960 and 1974 (OR 4.26, 95% CI 1.09-16.7). CONCLUSIONS: The results of this study do not support the findings of some earlier studies for an increased bladder cancer risk in the textile industry. However, some elevated risks were observed among the workers with the highest exposures. PMID- 11201395 TI - Acute myeloid leukemia and clonal chromosome aberrations in relation to past exposure to organic solvents. AB - OBJECTIVES: The effects of occupational and leisure-time exposures on the risk of acute myeloid leukemia (AML) were investigated with emphasis on clonal chromosome aberrations (CCA) and morphological subtypes. METHODS: Consecutively diagnosed cases of AML (N=333) and 1 population referent per case were retrospectively included in the study. Information on worktasks, companies, and leisure-time activities was obtained with telephone interviews. Exposure probability and intensity were assessed by occupational hygienists. Associations were evaluated with logistic regression. RESULTS: Exposure to organic solvents was associated with an increased risk of AML [low exposure: OR 1.5 (95% confidence interval (95% CI) 1.0-2.3, moderate-high exposure: OR 2.3 (95% CI 1.0-5.0)]. For exposure to solvents, but not to benzene, the OR was 1.2 (95% CI 0.69-2.0) for "low" and 2.7 (95% CI 1.0-7.3) for "moderate-high" exposure. The observed effects increased with intensity and duration of exposure. The estimated effects were higher for patients >60 years of age at the time of diagnosis. The effect of exposure to organic solvents was not differential with regard to morphology [except possibly erythroleukemia: OR 4.2, 95% CI 1.0-17 or the presence of CCA in general]. No increased risk for AML with complex CCA or with total or partial losses of chromosomes 5 or 7 were observed, but a higher risk was found for AML with trisomy 8 (OR 11, 95% CI 2.7-42) as the sole aberration. CONCLUSIONS: Exposure to organic solvents was associated with an increased risk of AML. This association was not due to benzene exposure alone and may be modified by age. Furthermore, specific associations with trisomy 8, and possibly also erythroleukemia, were suggested. PMID- 11201396 TI - Semen quality and sexual hormones in greenhouse workers. AB - OBJECTIVES: This study focused on determining the testicular function of greenhouse workers exposed to pesticides. METHODS: Semen was examined for 122 of 199 eligible men (61%) from 30 ornamental flower greenhouses. Sperm concentration, morphology, and viability were measured according to World Health Organization guidelines, and the curvilinear sperm velocity was determined by a computer-assisted analysis of video recordings. Three groups were formed according to expert judgment of current exposure to pesticides from cultures, pesticide formulations, and the transfer of pesticide residues from leaves to hands, and also ranked according to years of work in a greenhouse. The risk estimates were adjusted for the effects of sexual abstinence and other potentially confounding factors. RESULTS: According to current exposure the median values of sperm concentration and the proportion of normal spermatozoa were 60% and 14% lower, respectively, in the high-level exposure group (N=13) than in the low-level group (N=44), and the values of the intermediate group fell in between. The adjusted differences between the high-level and low-level exposure groups were statistically significant, while no differences were observed for the viability and velocity of sperm and sexual hormones. The median sperm concentration was 40% lower for the men with > 10 years' experience in a greenhouse than for those with < 5 years' experience. The age-adjusted testosterone/sex-hormone-binding globulin ratio declined 1.9% (95% confidence interval 0.4-3.4%) per year of work. CONCLUSIONS: The results are compatible with the hypothesis that male fecundity may be at risk from exposure to pesticides in the manual handling of cultures in greenhouses. PMID- 11201397 TI - Spontaneous abortions among veterinarians. AB - OBJECTIVES: The objective of the study was to determine whether female veterinarians have an increased risk of spontaneous abortion and whether the potential risk is related to the type of work veterinarians do. METHODS: The investigation was a retrospective cohort study among all the female members of the Finnish Veterinary Association (N=549). Information on pregnancies was obtained from hospital records from 1973-1990. The risk of spontaneous abortion among the veterinarians was compared with that of all other Finnish women and other upper-level employees. Odds ratios from logistic regression analyses were used as the estimates of the risk ratios. RESULTS: The risk of spontaneous abortion was 10.5% for the veterinarians. In the 1970s, practicing veterinarians had an increased risk of spontaneous abortion as compared with other Finnish women (adjusted odds ratio 1.8, 95% confidence interval 1.0-3.1) or other upper level employees (adjusted odds ratio 2.0, 95% confidence interval 1.1-3.4). In the 1980s, the risk fell below that of other Finnish women. No essential differences were observed in the risk between the veterinarians employed in different occupational categories. CONCLUSIONS: The results suggest that the veterinarians had an increased risk of spontaneous abortion in the 1970s, but not in the 1980s. Factors which might have contributed to this decrease in risk include decreases in the prevalence and level of exposure to harmful agents, improvements in the occupational hygiene of the work environment, and an increased awareness of reproductive hazards and the use of sick leave during pregnancy. PMID- 11201398 TI - Occupational risk factors for radial tunnel syndrome in industrial workers. AB - OBJECTIVES: The aim of the study was to evaluate both nonoccupational and occupational factors associated with radial tunnel syndrome (RTS) among industrial workers in 3 large plants. METHODS: Twenty-one cases of RTS were compared with 21 referents matched for gender, age, and plant. RTS was associated with carpal tunnel syndrome (CTS) in 9 cases. Past medical history, household activities, and ergonomic and organizational characteristics of the job were analyzed. RESULTS: The study found 3 occupational risk factors for RTS. Exertion of force of over 1 kg [odds ratio (OR) 9.1, 95% confidence interval (95% CI) 1.4 56.9] more than 10 times per hour was the main biomechanical risk factor. Prolonged static load applied to the hand during work was strongly associated with RTS (OR 5.9, 95% CI 1.2-29.9). Work posture with the elbow fully extended (0 45 degrees) was associated with RTS (OR 4.9, 95% CI 1.0-25.0). Full extension of the elbow, associated with a twisted posture of the forearm, stressed the radial nerve at the elbow. However, personal activities, household chores, and sport and leisure activities were not associated with RTS. CONCLUSIONS: The study confirms that RTS occurs in workers performing hard manual labor that requires forceful and repetitive movements involving elbow extension and forearm prosupination. PMID- 11201399 TI - Changes in the ocular and nasal signs and symptoms of aircrews in relation to the ban on smoking on intercontinental flights. AB - OBJECTIVES: This study determined the influence of exposure to environmental tobacco smoke (ETS) in aircraft on measured and perceived cabin air quality (CAQ), symptoms, tear-film stability, nasal patency, and biomarkers in nasal lavage fluid. METHODS: Commercial aircrews underwent a standardized examination, including acoustic rhinometry, nasal lavage, and measurement of tear-film break up time. Eosinophilic cationic protein, myeloperoxidase, lysozyme, and albumin were analyzed in the nasal lavage fluid. Inflight investigations [participation rate 98% (N=39)] were performed on board 4 flights, 2 in each direction between Scandinavia and Japan. Scandinavian crew on 6 flights from Scandinavia to Japan participated in postflight measurements after landing [participation rate 85% (N=41)]. Half the flights permitted smoking on board, and the other half, 0.5 months later, did not. Hygienic measurements showed low relative air humidity on board (2-10%) and a carbon dioxide concentration of <1000 ppm during 99.6% of the cruising time. RESULTS: The smoking ban caused a drastic reduction of respirable particles, from a mean of 66 (SD 56) microg/m3 to 3 (SD 0.8) microg/m3. The perceived CAQ was improved, and there were fewer symptoms, particularly ocular symptoms, headache and tiredness. Tear-film stability increased, and nasal patency was altered. CONCLUSIONS: Despite a high air exchange rate and spatial separation between smokers and nonsmokers, smoking in commercial aircraft may cause significant air pollution, as indicated by a large increase in respirable particles. This ETS exposure is associated with an increase in ocular and general symptoms, decreased tear-film stability, and alterations of nasal patency. PMID- 11201400 TI - Predictors of first nonfatal occupational injury following employment in a Brazilian steelworks. AB - OBJECTIVES: This study investigated the influence of sociodemographic and occupational factors on the risk of 1st injury among Brazilian steelworkers. METHODS: Workers 1st employed between 1 January 1977 and 31 December 1985 and still employed on 1 December 1983 were followed from the date of hire until 30 October 1992. Occupational injuries were ascertained from a database. Kaplan Meier curves for time to 1st injury were calculated for the total cohort and for different subgroups. A multivariate analysis of risk factors for 1st injury was carried out using the Cox proportional hazards regression model. RESULTS: Forty one percent of the workers had > or = 1 occupational injuries, and 39% of 1st injuries occurred in the 1st year of employment. Lacerations, contusions, penetration by foreign bodies, bums, sprains, and fractures constituted the main diagnostic groups. Injuries to the hands, eyes, feet, arms, and legs dominated. Over 5% of the injured workers were on temporary disability leave (cumulative total 10,660 days). The probability for an occupational injury was 16% for the 1st year, rising to 25% in the 2nd year. The risk of nonfatal injury was highest for laborers [hazard ratio (HR) 1.76, 95% confidence interval (95% CI) 1.35-2.29] and employees in the steel mill (HR 1.40, 95% CI 1.21-1.63), and inversely related to worker age and educational level. The risk of injury decreased significantly with calendar period of employment. CONCLUSIONS: Substantial reductions in nonfatal injuries may reflect changes in work organization, increased automation, and improved safety standards. Knowledge of predictors of work-related injury may contribute to injury prevention strategies, especially among newly employed workers. PMID- 11201401 TI - Cancer-preventive effects of sunscreens are uncertain. AB - Provocative findings have been published suggesting that the use of sunscreens may promote skin cancer. A recent meeting of international experts on the use of sunscreens and skin cancer was held at the International Agency for Research on Cancer in Lyon. The workshop concluded that the topical use of sunscreens reduces the risk of sunburn and that sunscreens probably prevent squamous-cell carcinoma of the skin when used mainly during unintentional sun exposure. No conclusion could be drawn about the cancer-preventive activity of topical sunscreens against basal-cell carcinoma and cutaneous melanoma. The use of sunscreens can extend the duration of intentional sun exposure, such as sunbathing. Such an extension may increase the risk for cutaneous melanoma. The workshop warned against relying solely on sunscreens for protection from ultraviolet radiation. PMID- 11201402 TI - The presence of atypical small acinar proliferation in prostate needle biopsy is predictive of carcinoma on subsequent biopsy. AB - OBJECTIVE: To determine the clinical significance of nondiagnostic small acini showing cellular atypia (atypical small acinar proliferation) in prostatic biopsies of patients with clinical findings suggestive of malignancy. PATIENTS AND METHODS: Of 331 patients who underwent thin-core biopsy of the prostate over a 30-month period, 21 (6.3%) had atypical histological features, and of these 17 underwent repeat biopsy. In addition, a further 20 patients with normal histology underwent repeat biopsy for persistent abnormal clinical findings. The incidence and Gleason score of carcinomas subsequently diagnosed in the two groups were compared. The predictive significance of patient age, prostate specific antigen (PSA) level and digital rectal examination (DRE) findings were compared between both patient groups, those in each group subsequently found to have carcinoma, and between patients with malignant or normal repeat biopsies who had either atypical or normal initial biopsies. RESULTS: Nine patients with atypical histology and four with normal histology on initial biopsy were found to have carcinoma on subsequent biopsy (P = 0.036). The site of carcinoma diagnosed in the repeat biopsy frequently differed from that of the initial atypical biopsy. The Gleason primary pattern was not significantly different between the groups. Neither patient age, PSA level nor DRE findings differed between patients with initial normal or atypical biopsy, or in these groups for those in whom carcinoma was subsequently diagnosed. These clinical features did not distinguish between those with carcinoma or normal findings on repeat biopsy who had an initial atypical biopsy, while only PSA level varied significantly in patients with normal or malignant repeat biopsy in the group with an initial normal biopsy. CONCLUSION: The presence of atypia on initial biopsy is a strong predictor of malignancy in subsequent biopsy specimens. PMID- 11201403 TI - Analysis and modelling of wear of cobalt-chrome alloys in a pin-on-plate test for a metal-on-metal total hip replacement. AB - The complex interaction between wear and bearing surfaces of two contacting solids was investigated in this study, with particular reference to the use of metal-on-metal material combinations for artificial hip joint replacements. The contact mechanics model was coupled with the wear model and solved simultaneously as a function of time for a simple case of a uniaxial pin-on-plate wear test. Both a spherical pin and a flat-ended spherical pin were considered. It was shown that the contact pressure between the pin and the plate was substantially reduced by the wear process, particularly during the initial running-in period and for the spherical pin. The theoretical prediction of the worn profiles of the pin and the plate was found to be in good agreement with previous experimental measurements by Tipper et al. in 1999. PMID- 11201404 TI - A hip joint simulator study using new and physiologically scratched femoral heads with ultra-high molecular weight polyethylene acetabular cups. AB - This study validates a hip joint simulator configuration as compared with other machines and clinical wear rates using smooth metal and ceramic femoral heads and ultra-high molecular weight polyethylene (UHMWPE) acetabular cups. Secondly the wear rate of UHMWPE cups is measured in the simulator with deliberately scratched cobalt-chrome heads to represent the type of mild and severe scratch damage found on retrieved heads. Finally, the scratching processes are described and the resulting scratches compared with those found in retrieved cobalt-chrome heads. For smooth cobalt-chrome and zirconia heads the wear rates were found to be statistically similar to other simulator machines and within the normal range found from clinical studies. An increased wear rate was found with cobalt-chrome heads scratched using either the diamond stylus or the bead cobalt-chrome but the greatest increase was with the diamond scratched heads which generated scratches of similar dimensions to those on retrieved heads. A greater than twofold increase in wear rate is reported for these heads when compared with smooth heads. This increased wear rate is, however, still within the limits of data from clinical wear studies. PMID- 11201405 TI - A method for the evaluation of the change in volume of retrieved acetabular cups. AB - Studies on retrieved hip prostheses are currently performed in order to assess the wear mechanisms and the overall wear rate of such artificial joints. Several reported studies on the survival of artificial hips have been based on the measurement of the amount of worn material directly on retrieved acetabular cups. The estimation of the change in volume, V, of the cup cavity is particularly difficult in the case of slight wear due to several factors of which the most critical is the lack of information on the unworn geometry of the cup. This paper presents a new measuring technique, which is described in detail and has been applied to estimate the wear of 65 acetabular cups harvested from revised hip arthroplasty. The coordinate data of several points on the articular surface are sampled using a coordinate measuring machine (CMM). The value of V is calculated mathematically from the measurements by using the hypothesis that the actual shape of both slightly worn and highly worn surfaces has a small departure from a truly spherical shape. The wear volume is estimated with reasonable accuracy mainly on those cups showing penetration depths greater than 0.2 mm, corresponding to an amount of wear greater than 100 mm3 for a 32 mm cup. The uncertainty in the results is estimated for each cup. The repeatability of the technique is studied for a case showing very slight wear. The advantages, disadvantages and limitations of the method are presented and discussed. PMID- 11201406 TI - An investigation of three-dimensional scanning of human body surfaces and its use in the design and manufacture of prostheses. AB - The capture of highly accurate data describing the complex surfaces of the human body may prove extremely useful in many medical situations. The data provide a method of measuring and recording changes to the surface of a patient's soft tissue. The data may be applied to computer-controlled manufacturing techniques, such as rapid prototyping (RP). This enables accurate physical replicas of the patient topography to be produced. Such models may be used as an aid in the design and manufacture of prostheses. This paper describes an investigation aimed at identifying problems that may be encountered when scanning patients and describes the application of the resulting data in the design and manufacture of facial prostheses. The results of the experiment are presented together with a discussion of the accuracy and potential advantages afforded by this approach. PMID- 11201407 TI - Finite element analysis of bone stress and strain around a distal osseointegrated implant for prosthetic limb attachment. AB - Direct skeletal attachment techniques have recently been identified as an alternative method for percutaneous attachment of prosthetic limbs. Osseointegrated implants for prosthetic attachments are subjected to a complex load condition. This finite element study investigates the effect of varying geometries of the implant on the stress and strain distribution in the area of the bone/implant interface. Simplified three-dimensional axisymmetric models of the femur and seven implants with different core diameters, external diameters, implant lengths and thread pitches were derived. The resulting stress and strain distributions were compared. The significance of each implant geometry was identified for improving implant design in the light of benefit to the bone/implant osseointegration and the bone remodelling of the femur. PMID- 11201408 TI - The design and testing of a composite lower limb prosthesis. AB - In unilateral lower limb prosthetic gait, the intact limb, together with the hip on the affected side, strive to compensate for the loss of the missing below-knee musculature. The resultant abnormal gait patterns can eventually lead to pathologies of the spine and other joints. The aim of this research was to design a trans-tibial dynamic elastic response (DER) prosthesis which could simulate the power generation and absorption properties of an intact foot and shank segments. A carbon fibre sickle-shaped prosthesis was developed in which the strain energy from the early part of the stride was stored, and was released again at the point of take-off, to simulate the action of the missing musculature. Stress analysis techniques were used in the design of the prosthesis, for the purposes of computing and maximizing the strain energy of the elements. A force transducer was designed into the prosthesis to verify the analysis. Video motion analyses of the prosthesis were carried out in order to determine the most appropriate shape that would reduce gait asymmetries. The research shows that biomechanical techniques, together with good engineering design and the selection of modern materials, can lead to a prosthesis which approaches the function of a natural foot. PMID- 11201409 TI - Pliable polylactide plates for guided bone regeneration: manufacturing and in vitro. AB - Three different types of pliable and bioabsorbable plates, 0.4 mm thick, were developed for guided bone regeneration to cover cranial defects. The processing (extrusion, melt-spinning, knitting and heat pressing) and in vitro degradation of the materials were studied. Materials used were poly-L,DL-lactide with an L/DL ratio of 70/30 (PLA70) and poly-L,D-lactide with an L/D ratio of 96/4 (PLA96). The initial tensile strengths of gamma-sterilized PLA96, PLA70 and the PLA70 PLA96 composite plates were 45.7 +/- 3.8, 51.2 +/- 3.6 and 24.7 +/- 5.1 MPa respectively. The composite plates were the stiffest and lasted for more than 24 weeks. The glass transition temperature (Tg) of both polymers decreased in vitro. The crystallinity of PLA96 increased tenfold within 18 weeks. For initially amorphous PLA70 the highest melting enthalpy was 89 J/g at 60 weeks. PLA70 became partially crystalline and the plates changed from transparent to white and swollen. Extrusion and sterilization decreased the initially different molecular weight (Mw) values to the same level. After 18 weeks of hydrolysis, Mw was 15,000 Da for PLA96 and 12,000 Da for PLA70. For the components of the composite plate Mw was 15,000 Da for the PLA70 plate and 27,000 Da for the PLA96 mesh. Morphologically, all the hydrolysed plates retained, for a long period, a solid surface layer under which a porous structure formed. Crystalline branches and some single crystals were seen. The composite plates had the slowest degradation rate and they remained intact the longest. PMID- 11201410 TI - Anisotropic response of the human knee joint meniscus to unconfined compression. AB - The response of meniscal tissue to axial, radial and circumferential compressive forces was measured at physiologically relevant levels of load in eight pairs of human knee joint menisci. Compression was unconfined and uniaxial. Stress strain data were fitted to a two-parameter exponential model. The tissue was found to be significantly stiffer to axial compressive forces than to radial and circumferential forces. No significant difference was found between the responses to circumferential and radial forces. PMID- 11201411 TI - Glenohumeral contact forces. AB - Glenohumeral contact forces have only been calculated previously either for simple abduction or for athletic activities. The objective of this study was to determine the glenohumeral contact forces for tasks which are demanding of the shoulder but which would commonly be performed by older people. The functional tasks chosen were using the arms to stand up from and sit down into a chair, walking with a cane, lifting a 5 kg box to shoulder height with both hands, and lifting a 10 kg suitcase. The trunk angles, arm angles and hand loads of six healthy subjects, average age 55 years, were recorded. This information was input into a biomechanical computer model which optimized the muscle force distribution by minimizing the sum of squared muscle stresses subject to constraints on the maximum muscle forces and maintaining the direction of the resultant force within the glenoid fossa. Average contact forces ranged from 1.3 to 2.4 times body weight (930-1720 N), the highest force being for lifting a suitcase. This latter value would be even higher if lifting either a greater load or to a greater height. Thus, contact forces at the shoulder should not be underestimated. This study provides functionally relevant contact forces which can be used for mechanical testing or finite element modelling of shoulder prostheses. PMID- 11201412 TI - Development of a computer model to predict pressure generation around hip replacement stems. AB - Cemented fixation of hip replacements is the elective choice of many orthopaedic surgeons. The cement is an acrylic polymer which grouts the prostheses into the medullary cavity of the femur. Cement pressure is accepted as a significant parameter in determining the strength of cement/bone interfaces and hence preventing loosening of the prostheses. The aim of this work was to allow optimal design of the intramedullary stem of a hip prosthesis through knowledge of the flow characteristics of curing bone cement which can be used to predict pressures achieved during insertion of the femoral stem. The viscosity of the cement is a vital property determining the cement flow and hence cement interdigitation into bone. The apparent viscosities, nu(a), of three commercial bone cements were determined with respect to time by extrusion of the curing cement through a parallel die of known geometry under selected pressures. Theoretical models were developed and implemented in a computer program to describe cement flow in three models each of increasing complexity: (a) a simple parallel cylinder, (b) a tapered conical mandrel and (c) an actual femoral prosthesis, the latter models being complicated by extensional effects as annular areas increase. Predicted pressures were close to those measured experimentally, maximum pressures being in the range 10-160 kPa which may be compared with a threshold of 76 kPa proposed for effective interdigitation with cancellous bone. The theoretical model allows the prosthesis/bone geometry of an individual patient to be evaluated in terms of probable pressure distributions in the medullary cavity during cemented fixation and can guide stem design with reference to preparation of the medullary canal. It is proposed that these models may assist retrospective studies of failed components and contribute to implant selection, or to making informed selection from options in custom hip prosthesis designs to achieve optimum cement pressurization. PMID- 11201413 TI - Stress distribution in the dento-alveolar system using digital photoelasticity. AB - Past research has confirmed that the governing factors in cellular modelling and remodelling adhere to sound principles of engineering mechanics. Hence studies of stress distributions would provide better understanding of the functional adaptation of dental supporting structures. Photoelasticity is an established experimental tool to study whole-field stress distribution in structures subjected to forces. However, it has certain limitations that make its application in biological specimens tedious. In this investigation an advanced digital photoelastic system is used to visualize and study the nature of the stress distribution in dental supporting structures. These digital fringe patterns are analysed using a phase-shift technique. The present biomechanical study shows that dental supporting structures exhibit a characteristic stress distribution, promoting structural adaptation based on needs. Furthermore, the advantage of using a digital image processing system along with the circular polariscope is discussed. PMID- 11201414 TI - The effects of different wire and screw combinations on the stiffness of a hybrid external fixator. AB - Hybrid external fixators that use tensioned wires in the metaphysis and screws in the diaphysis combine the advantages of both unilateral and circular fixators and provide considerable flexibility in frame construction. This study aims to determine the effects of wire and screw combinations on the mechanical characteristics of such systems. Acrylic rods were used to simulate a long bone with a transverse fracture gap. A standard hybrid fixator design was used to stabilize the fracture in accordance with modern concepts with wires being used on one side of the fracture and screws on the other side. Twelve different wire and screw combinations were tested in axial compression and four-point bending in two planes. All the fixators tested demonstrated stiffening under increasing axial load, the extent of which appeared to correlate inversely with the number of wires used. Increasing the number of wires by one increased the axial stiffness by 7-16 N/mm (average 11 N/mm). The bending stiffness was largely controlled by the number of wires and increased by 0.42-1.03 N m/mm (average 0.74 N m/mm) for each additional wire. The axial stiffness of fixators with three screws was 4-7 N/mm (average 6 N/mm) higher than those with two screws if the offset screw was not in use. When the offset screw was used no stiffness advantages were found for three screws over two screws. The use of an offset screw substantially increased axial stiffness (by 12-26 N/mm, average 20 N/mm) and is recommended for unstable fractures. The two-ring hybrid fixators with four wires in one ring and three screws in the other had stiffness characteristics similar to the conventional four-ring Ilizarov fixator. Knowledge gained regarding the effects of wire and screw combinations on overall stiffness will be helpful both in the construction of frames and in destabilization during fracture healing. PMID- 11201415 TI - Characterization of vortices using pulsed-wave Doppler ultrasound. AB - The detection and characterization of vortices from a Kaman vortex generator by means of a 20 MHz pulsed-wave Doppler ultrasound system were assessed. Measurements were made at different steady flowrates in a 10 mm internal diameter polyurethane tube, 14 mm distal to a circular cylinder of diameter 2 mm, placed across the tube inlet. The results were compared with those obtained with a two component laser Doppler anemometer system. There was generally good agreement between the two techniques in the measurement of convective flow velocity, frequency of vortex shedding and the circulation velocity of the vortices. It is concluded that pulsed-wave Doppler ultrasound is a suitable technique for investigating vortical flow structures. PMID- 11201416 TI - Friction in orthopaedic zirconia taper assemblies. AB - The torque resistance of zirconia ceramic heads/titanium taper trunnion junctions was tested in accordance with ISO 7206-9:1994(E); using twelve modified heads of 32 mm diameter under representative physiological conditions. Test parameters studied included assembly force, vertical load during test (test load) and head length. Mean torque resistances measured were 8.9 N m for a 1 kN test load and 15 N m at 4 kN test load. Coefficients of friction calculated for the torsional stability ranged from 0.06 to greater than 1.0. Multiple regression analysis confirmed that the failure torques measured were significantly dependent on test load (beta = 0.77; P < 0.001) whereas assembly force and head length played a lesser, insignificant, part in the variation. Data from push-on/pull-off tests were used to calculate coefficients of friction under axial loading, which were significantly correlated with taper angle and material. Torque testing shows greater variability than push-on/pull-off tests for similar combinations, and for zirconia heads on other tapers. The coefficients of friction measured (0.16-0.31) are significantly different from values typically used in stress analyses. PMID- 11201417 TI - Independent ambulators with high sacral myelomeningocele: the relation between walking kinematics and energy consumption. AB - The aims of this study were to determine the relation between gait kinematics (center of mass excursions) and measures of oxygen consumption and oxygen cost. Fourteen independent ambulating children with myelomeningocele (nine females, five males; mean age 8 years 7 months) and thirteen children with no history of neuromuscular disorder were evaluated. At their comfortable walking speed all patients exhibited oxygen cost and oxygen consumption values that exceeded the normal level by more than 1 SD. Pelvic obliquity demonstrated the strongest relation with oxygen cost which suggests that ultimately hip abductor strength may play a key role in energy demands during gait. Despite the exaggerated pelvic kinematics, vertical and horizontal center of mass excursions of the trunk and whole-body during the gait cycle were not significantly greater than normal (p>0.05). Decreased self-selected walking velocity at which many of these children consider comfortable and stable may be predicated on an optimal center of mass movement that approximates the magnitude observed in normal gait. The slower walking velocity decreases walking efficiency. Conversely, the increased center of mass movement that would accompany a faster gait would probably impose intolerable oxygen consumption levels. Strengthening programs that focus on the gluteus medius and maximus to decrease compensatory trunk and pelvic motions, allowing the patients to adopt a faster gait without exacerbating kinematic and center of mass motions and which enabled more efficient walking hold promise for these patients. PMID- 11201418 TI - Developmental patterns of rhythmic suck and swallow in preterm infants. AB - Twenty healthy preterm infants (gestational age 26 to 33 weeks, postmenstrual age [PMA] 32.1 to 39.6 weeks, postnatal age [PNA] 2.0 to 11.6 weeks) were studied weekly from initiation of bottle feeding until discharge, with simultaneous digital recordings of pharyngeal and nipple (teat) pressure and nasal thermistor and thoracic strain gauge readings. The percentage of sucks aggregated into 'runs' (defined as > or = 3 sucks with < or = 2 seconds between suck peaks) increased over time and correlated significantly with PMA (r=0.601, p<0.001). The length of the sucking-runs also correlated significantly with PMA (r=0.613, p<0.001). The stability of sucking rhythm, defined as a function of the mean/SD of the suck interval, was also directly correlated with increasing PMA (r=0.503, p=0.002), as was increasing suck rate (r=0.379, p<0.03). None of these measures was correlated with PNA. Similarly, increasing PMA, but not PNA, correlated with a higher percentage of swallows in runs (r=0.364, p<0.03). Stability of swallow rhythm did not change significantly from 32 to 40 weeks' PMA. In low-risk preterm infants, increasing PMA is correlated with a faster and more stable sucking rhythm and with increasing organization into longer suck and swallow runs. Stable swallow rhythm appears to be established earlier than suck rhythm. The fact that PMA is a better predictor than PNA of these patterns lends support to the concept that these patterns are innate rather than learned behaviors. Quantitative assessment of the stability of suck and swallow rhythms in preterm infants may allow prediction of subsequent feeding dysfunction as well as more general underlying neurological impairment. Knowledge of the normal ontogeny of the rhythms of suck and swallow may also enable us to differentiate immature (but normal) feeding patterns in preterm infants from dysmature (abnormal) patterns, allowing more appropriate intervention measures. PMID- 11201419 TI - Contact and nutrient caregiving effects on newborn infant pain responses. AB - To understand how the 'caregiving context' could affect responses to procedural pain, the authors sought to determine whether (1) the combined effects of sweet taste and holding (caregiving contact) were greater than the effects of either alone, (2) any combined effects were additive or interactive, and (3) the interventions had similar effects on behavioral (crying and facial activity) and physiological (heart rate, vagal tone) responses to the heel-stick procedure in newborn infants in a randomized two-factorial intervention trial. Eighty-five normally developing newborn infants were studied with a mean gestational age of 39.4 weeks on the 2nd or 3rd day of life. Infants were randomized in blocks of eight to receive (1) no holding and water taste (control participants), (2) no holding and sucrose taste (sucrose group), (3) holding and water taste (holding group), or (4) holding and sucrose taste (holding and sucrose group). Crying was reduced significantly by taste and holding, and the interventions combined additively. Facial activity was only significantly reduced by holding. For physiological measures, the interventions interacted with each other and preintervention levels to reduce heart rate and lower vagal tone more during the procedure in infants in whom heart rate and vagal tone were higher before intervention. Consequently, sweet taste and holding interventions combined in complex ways when acting on different behavioral and physiological response systems to modify stressful pain experiences. The results suggest that providing a caregiving context when painful procedures are performed may be a simple and practical method of reducing pain experience in infants, and that no one measure captures these effects. PMID- 11201420 TI - Does 'therapy' have a future? PMID- 11201421 TI - Feeding problems in Silver-Russell syndrome. AB - In order to identify the prevalence and severity of feeding problems in children with Silver-Russell syndrome (SRS) the feeding difficulties of 32 children with SRS and 32 age- and sex-matched control children were assessed using the Feeding Assessment Questionnaire (Harris and Booth 1992). Children's ages ranged from 2 to 11 years, with 19 male and 13 female pairs. In a subset of matched pairs, parent-child interaction at mealtimes was examined using video recording; food intake was also assessed over a 3-day period using weighed food diaries. Children with SRS experienced significantly more feeding problems than children without growth disorders. Common feeding problems for children with SRS were poor appetite, fussiness, slow feeding, and problems associated with oral-motor dysfunction. Feeding problems did not significantly affect intake of kilocalories, protein, fat, or carbohydrates. Mealtime interaction between children with SRS and their parents was significantly more negative than interactions between control-group children and their parents. The focus of intervention packages in SRS should be to reduce negative parent-child interactions and reduce parental anxiety about feeding, growth, and weight. PMID- 11201422 TI - Randomized controlled trial of physiotherapy in 56 children with cerebral palsy followed for 18 months. AB - This study aimed to determine whether motor function and performance is better enhanced by intensive physiotherapy or collaborative goal-setting in children with cerebral palsy (CP). Participants were a convenience sample of 56 children with bilateral CP classified at level III or below on the Gross Motor Function Classification System (GMFCS), aged between 3 and 12 years. A 2 x 2 factorial design was used to compare the effects of routine amounts of physiotherapy with intensive amounts, and to compare the use of generalized aims set by the child's physiotherapist with the use of specific, measurable goals negotiated by the child's physiotherapist with each child, carer, and teacher. Following the six month treatment period there was a further six-month period of observation. Changes in motor function and performance were assessed by a masked assessor using the Gross Motor Function Measure (GMFM) and the Gross Motor Performance Measure (GMPM) at three-month intervals. There was no statistically significant difference in the scores achieved between intensive and routine amounts of therapy or between aim-directed and goal-directed therapy in either function or performance. Inclusion of additional covariates of age and severity levels showed a trend towards a statistically significant difference in children receiving intensive therapy during the treatment period. This advantage declined over the subsequent six months during which therapy had reverted to its usual amount. Differences in goal-setting procedures did not produce any detectable effect on the acquisition of gross motor function or performance. PMID- 11201423 TI - Classification criteria and distinction between migraine and tension-type headache in children. AB - The International Headache Society (IHS) classification system (1988) was developed primarily for headache disorders in adults and its validity for paediatric age is currently under discussion; in 1995 Seshia et al. proposed a revision of the criteria for migraine without aura to make diagnostic criteria more applicable to children. The purposes of the current study were to: (1) compare the IHS classification with the Seshia proposal, (2) compare the children affected by migraine without aura (MO) with the children affected by tension headache (TH) as defined by Seshia, for characteristics which are not included in the classification. The patients are a series of 320 children (mean age 9.9, SD 2.6 years; 144 males, 176 females) with recurrent or chronic headaches referred to a headache clinic in Milan, Italy. Using the Seshia criteria instead of the IHS criteria a higher number of children were included in the MO category: bilateral pain and family history of migraine were the most important factors which allowed a shift of children into this category. However, with the Seshia classification there was no reduction in the number of unclassifiable children. The reason why some children could not be classified was a short duration of attacks; the majority of unclassifiable children were 6 years old or less. No relevant difference was found between children with MO and children with TH for the following variables: occurrence of attacks in the afternoon or evening after school, reduction of attacks during school holidays, full-time schooling, after school activities on school days, disordered daily life. On the contrary children with MO when compared with those with TH showed a higher number of precipitating factors and for the following factors a significant difference was found: exposure to TV or a computer, sleep deficiency, and strong emotions. Furthermore, children with MO showed a greater severity of attacks. PMID- 11201424 TI - Brain injuries in early foetal life: consequences for brain development. AB - Learning disability and cerebral palsy are often related to factors present before birth. We report three patients (two with schizencephaly, one with unilateral cerebellar agenesis) in whom the timing of an insult to the foetus was known. In the first case, the mother had a trauma at 16 weeks of pregnancy and schizencephaly was discovered in the male infant associated with a left hemiplegia. In the second child, amniocentesis performed at 16 weeks into pregnancy may have been responsible for the same cortical anomaly. In the third case, sequential foetal echographies clearly demonstrated that an apparent unilateral cerebellar agenesis was related to an haemorrhagic event secondary to cerebellar trauma that occurred at 19 weeks of pregnancy. It is suggested that these brain malformations are related to an ischemic mechanism or a traumatic event in foetal life. PMID- 11201425 TI - Recent advances in cortical visual impairment. PMID- 11201426 TI - Intrauterine growth retardation, general movements, and neurodevelopmental outcome: a review. PMID- 11201427 TI - Guillain-Barre syndrome: a patient's experience. PMID- 11201428 TI - Self-esteem in children with physical disabilities. PMID- 11201429 TI - Analysis of psychomotor development of ten children with Moebuis syndrome. PMID- 11201431 TI - Potential of hazelnut husks as a broiler litter material. AB - 1. Hazelnut husks and some other litter materials were compared for litter properties and their effects on broiler performance. 2. A total of 750 1-d-old broiler chicks were weighed and assigned at random to 1 of 5 treatments, with each treatment replicated 3 times. 3. The treatments were wood shavings (control), wheat stalks, rice hulls, hazelnut husks, and a mixture of 50% rice hulls and 50% hazelnut husks. 4. Although hazelnut husks were associated with lower body weights at 49 d of age, food efficiency mortality, carcase yield, breast blisters and production index were similar to birds on wood shavings. Hazelnut husks had the highest litter moisture. 5. The results show that hazelnut husks alone and when mixed with rice hulls are a potential alternative litter material for broiler production. PMID- 11201430 TI - Long term dynamics of dermanyssus gallinae in relation to mite control measures in aviary systems for layers. AB - 1. The dynamics of the poultry red mite, Dermanyssus gallinae, in aviary systems for layers were studied in an empirical study in Sweden between 1994 and 1997. Fluctuations were monitored with mite traps at monthly intervals during 3 laying cycles at each of 2 commercial poultry farms. 2. When mites were first detected in the system it then took about 5 months for the populations to reach equilibrium levels around which they fluctuated. Within flocks when the population growth was unaffected by temporary control activities, it was demonstrated that the mite populations were significantly denser in summer than in winter. 3. Current control methods had limited effects as mite populations were only temporarily suppressed. One exception was the control achieved with permethrin impregnated plastic strips, which reduced the population at equilibrium level to approximately 22%, compared with the previous flock. 4. The distribution of mites was patchy horizontally, along the aviary system, at low burden wlhereas it became more evenly dispersed at equilibrium. 5. Significant differences in vertical mite distributions that correlated with the hybrids used and their rearing conditions were also observed. In flocks with brown hens, mites gathered at the lower tiers, whereas they were found at the highest tiers in association with white hens. As the hens are attacked mainly at night-time the most likely explanation is that the mites adjust their behavioural pattern to the birds' roosting behaviour. PMID- 11201432 TI - Small intestinal development in the young chick: crypt formation and enterocyte proliferation and migration. AB - 1. Post-natch mucosal development was examined in the chick small intestinal epithelium using immunostaining with proliferating cell nuclear antigen (PCNA) and 5-bromo-2-deoxyuridine (BrdU). 2. On the day of hatching jejunal crypts were small and a single crypt per villus was observed. However, during the 108 h post hatch crypts developed rapidly branching and increasing in size, cell numbers and cell size. 3. Almost all epithelial cells in the small intestine of the hatching chick were proliferating, as indicated by PCNA and BrdU, while more than 80% of proliferating cells were localised in the crypts after 108 h post hatch. 4. Estimate of villus cell transit time using BrdU was only possible from 48 h post hatch when villus transit time was 72 h in the jejunum, whereas at 336 h transit time was 96 h. 5. In the 108 h post hatch a rapid transition occurs from total jejunal epithelial cell proliferation and immature crypts to a defined proliferative zone in the crypts, with constant division and migration. PMID- 11201433 TI - Genetic effects of ageing on fertility and hatchability in the first laying cycle of three white leghorn strains and their two-way crosses. AB - 1. Fertility and hatchability of 3 White Leghorn strains and their 2-way crosses were examined in the 1st laying cycle to evaluate the effects of ageing on mean heterosis, reciprocal effects, additive (A), Z-chromosomne (Z) and heterotic effects (H), as well as on their variances. 2. Fertility and hatchability were evaluated at 37, 47 and 70 weeks of age for hens housed 1 per cage in a randomised block design. The mean heterosis was significant over time and increased with advancing age for both traits. Reciprocal effects were not significant across periods and did not show a consistent trend with age. 3. The pattern of age changes in A, Z and H effects varied among strains, indicating genotypic differences in response to ageing. The additive, heterotic, environmental and phenotypic variances increased at the end of the cycle for both traits, except for the additive variance of hatchability, which increased until 47 weeks of age but declined thereafter. 4. Heritability increased with age for fertility but did not show a consistent pattern across the cycle for hatchability. Genetic variance for fertility and hatchability increased at the end of the cycle, stggesting that improvement in performance during the 1st production cycle of layers could be achieved by selecting animals at older ages. PMID- 11201434 TI - Effects of divergent selection for incidence of tibial dyschondroplasia (TD) on purebred and crossbred performance. 1. TD incidence and calcium and phosphorus plasma concentrations. AB - 1. The effect of divergent selection for high (H) or low (L) incidence of tibial dyschondroplasia (TD) for 7 generations on blood calcium (Ca) and phosphorus (P) concentrations was studied. 2. The chicks used in this experiment were obtained from diallel crosses between H and L lines to obtain HH, HL, LH, and LL lines. A random-bred control (CC) line was also used. 3. The chicks were reared under standard management conditions. Body weight and plasma Ca and P concentrations were measured at 2, 4, and 7 weeks of age. Incidence of TD was recorded at 4 and 7 weeks. 4. Although HH birds had lower body weights than the other lines, there was no significant effect attributable to line selection for body weight at 2, 4, and 7 weeks of age. 5. The LL line birds had no incidence of TD at 4 weeks of age; however, the incidence of TD in LL line birds was 5.3% at 7 weeks of age. The incidence of TD was higher in HH line birds than the other line at 4 and 7 weeks of age. 6. Plasma Ca and P concentrations and Ca:P ratios increased with age. These results showed that HH line birds had higher plasma Ca, lower plasma P and higher Ca:P ratios than birds of the LL line. PMID- 11201435 TI - Effects of divergent selection for incidence of tibial dyschondroplasia (TD) on purebred and crossbred performance. 2. Processing yield. AB - 1. An experiment was conducted to determine the effect of selection for high (H) or low (L) incidence of tibial dyschondroplasia for 7 generations on processing performance of broilers. 2. Birds were obtained from diallel matings of the H and L lines (HH, HL, LH, and LL) and a randombred control (CC) line. Birds were reared to 7 weeks of age under standard management conditions. All birds were processed at 7 weeks of age. Body weight at 7 weeks, carcase weight, and carcase part weights were recorded on each bird. 3. An interaction between sire line and dam line was caused by lighter body and carcase weight at 7 weeks of age in HH birds than from the birds of the other crosses. 4. Birds by L line dams had heavier drumstick weights. The influences of sire line and dam line on weight of total breast muscle were not significant. Thigh weights and Pectoralis minor weights were lighter in HH line birds than those other matings. 5. Heterosis for body weight and for weights of carcases, drumstick and thigh was negative. Total breast muscle weight and P. major weight did not show significant heterosis. 6. It was concluded that selecting against TD does not reduce processing yield of broilers. PMID- 11201436 TI - Myofibre composition and total collagen content in M. iliotibialis lateralis and M. pectoralis of Silkie and White Leghorn chickens. AB - 1. Using adult Silkie and White Leghorn (WL) chickens, fibre composition and total collagen content were compared between M. iliolibialis lateralis (ITL) and M. pectoralis (PT). 2. Fibres were divided into type IIR and IIW showing strong and weak reduced nicotinamide adenine dinucleotide dehydrogenase activities, respectively. 3. Fibre composition differed markedly between ITL and PT muscle. ITL muscle was composed of both types IIR and IIW fibre but PT muscle of only type IIW Breed difference on composition was noted only in ITL muscle of cocks (type IIR; Silkie 53.8% and WL 37.0%). 4. Total collagen content was greater in ITL muscles and in cocks in both muscles. However, a breed difference was observed only in the PT muscle of hens. 5. In conclusion, the total collagen content was affected by muscle location within the body and by sex rather than by fibre composition. PMID- 11201437 TI - Investigation of hygiene aspects during air chilling of poultry carcases using a model rig. AB - 1. An experimental rig, designed and built to simulate conditions found in commercial poultry chilling systems, was used to investigate the effects of varying air temperature and chilling duration, and the effect of chlorinated water sprays, on the microbial load present on the skin and in the body cavity of freshly eviscerated poultry carcases; deep muscle and skin temperatures were monitored during chilling at three different temperatures. 2. During dry chilling for 2 h, total viable microbe counts (TVC) and counts of coliforms and pseudomonads from the body cavity fell by between half and one log unit; smaller reductions were observed in samples from the breast skin. 3. The situation changed when chlorinated water sprays (50, 100 or 250 ppm available chlorine) were applied for the first hour of chilling; spraying carcases enhanced the reduction in numbers on the skin; the effect was most pronounced with 250 ppm chlorine; conversely in the body cavity, the general effects of sprays was to increase contamination by up to one log unit. 4. There was no evidence that sprays increased the rate of chilling. 5. When carcases were held overnight in the rig at 11 degrees C after chilling, microbe counts on dry-chilled carcases remained stable, but increased on carcases that had been sprayed with chlorinated water. PMID- 11201438 TI - Ultrastructural analysis of the eggshell: contribution of the individual calcified layers and the cuticle to hatchability and egg viability in broiler breeders. AB - 1. Scanning electron microscopy was used to assess the relationship between the layers of the eggshell and egg viability. The relative thickness (absolute and %) of the mammillary, palisade, vertical crystal and cuticle layers relative to the total eggshell were measured over a 30-week laying period in 2 broiler breeder lines having different hatchability rates. 2. A significant difference in hatchability of 5.5% between the breeder lines was observed. However, there was no significant difference in either egg viability or fertility between lines. 3. The relative thickness of the individual calcified layers and the cuticle did not differ between lines. Therefore, variations in the thickness of the individual eggshell layers are unlikely to explain the 5.5% difference in hatchability rate between lines. 4. The thickness of the calcified region did not alter as the broiler hen aged. However, the percent contribution of each calcified layer significantly differed over the egg production period. 5. The cuticle was significantly thinner at the beginning and at the end of the laying period compared to 38 weeks of age. 6. No significant correlation was observed between egg viability and the relative thicknesses of the mamillary, palisade or cuticle layers. In contrast, there was a positive relationship between egg viability and the thickness of the vertical crystal layer. 7. The percent contribution of the mammillary and palisade layers was similar in the thinnest and thickest eggshells, suggesting conservation of the proportions of these layers independent of eggshell thickness. PMID- 11201439 TI - Growth performance and immune response of two commercial broiler strains fed diets containing Lactobacillus cultures and oxytetracycline under heat stress conditions. AB - 1. Hubbard x Hubbard (HH) and Shaver x Shaver (SS) chicks given a dietary supplement of either 50 mg/kg oxytetracycline (OTC) or 1 g/kg Lactobacillus culture (LC) were exposed to 36 +/- 1 degrees C for 3 h daily from day (d) 21 to 42. 2. Prior to heat treatment, body weight (d 21) and weight gain (d 1 to d 21) of OTC and LC birds were greater than those fed the control diet. Chicks given LC had the best food efficiency followed by OTC and control birds during d 1 to d 21. Body weight (d 1 and d 21) and weight gain (d 1 to d 21) were greater for HH tlhan SS chicks. 3. After 3 weeks of heat exposure, birds receiving the LC diet had greater body weight and weight gain, higher food intake and lower food efficiency than OTC and control chicks. 4. Antibody production against Newcastle discase vaccine on d 21 was not affected by strain or diet. On d 42, while diet had negligible effect on this variable among the SS broilers, HH birds fed LC had higher antibody production than those on the control diet. 5. Neither strain nor diet had a significant effect on mortality. PMID- 11201440 TI - Effect of excess dietary sodium, potassium, calcium and phosphorus on excreta moisture of laying hens. AB - 1. Four experiments were conducted to investigate the effects of dietary concentrations of sodium, potassium, calcium or phosphate on the water intake and excreta moisture of laying hens. A fifth experiment examined the effect on these variables of increasing amounts of 2 different sodium salts (chloride or bicarbonate) and the interactions with 2 levels of dietary phosphorus. 2. All experiments involved individually caged laying hens fed on diets varying in 1 or 2 minerals in replacement for washed sand. The experimental diets contained mineral concentrations that either met or exceeded the expected requirement of the hens. The diets were given for a 7 or 8 d feeding period and food and water intakes were measured and excreta were collected for the last 48 h of each feeding period. These data were corrected for evaporative water loss to the environment during the collection period. 3. Increasing dietary concentrations of sodium, potassium or phosphorus gave linear increases (P<0.001) in the water intake of the laying hens and linear increases (P<0.01) in the moisture content of their excreta. Each 1 g/kg increase in dietary mineral increased the moisture content of the excreta by 9.04 (+/- 1.57), 11.95 (+/- 2.02) and 5.59 (+/- 0.31) g/kg (+/- standard error) for sodium, potassium and phosphorus, respectively. Increasing concentrations of dietary calcium did not significantly affect the water intakes or excreta moisture levels of the laying hens. 4. The fifth experiment showed that, although there was a sodium x phosphorus interaction (P<0.05), the effects of the 2 mineral additions were approximately additive. There were no significant differences (P>0.05) in water intakes or excreta moisture contents due to the 2 different sodium salts (chloride or bicarbonate). PMID- 11201441 TI - Influence of dietary fat source and copper supplementation on broiler performance, fatty acid profile of meat and depot fat, and on cholesterol content in meat. AB - 1. Three hundred and twenty d-old chickens were fed on a wheat/maize-soyabean meal diet supplemented with (i) 50 g/kg lard, (ii) 25 g/kg lard and 25 g/kg rapeseed oil, (iii) 50 g/kg rapeseed oil, and (iv) 50 g/kg rapeseed oil and 200 mg copper per kg as copper sulphate pentahydrate. 2. Final weights at 39 d of age in chickens receiving rapeseed oil were lower by 9% than in those fed on the diet containing only lard (P<0.05). The fatty acids profiles of lipids extracted from the tissues of 10 chickens per group reflected those of the diets. 3. The polyunsaturated fatty acid (PUFA) content of breast muscles and abdominal fat (expressed as a percentage of total fatty acids) was increased and the ratio of n 6:n-3 fatty acids was decreased by the substitution of lard by rapeseed oil (P<0.001). These changes were more pronounced for the adipose tissue than for breast muscles. 4. Copper sulphate supplementation increased the final body weight of chickens by 4.3% (P<0.05), reduced the saturated fatty acid (SFA) proportion (P<0.05) in abdominal fat and increased the PUFA:SFA ratio (P<0.05). The magnitude of improvement, however, was small. 5. The substitution of rapeseed oil for lard decreased the concentration of cholesterol in breast muscles by 13%. Copper supplementation further reduced the cholesterol content by 25%. Both effects were significant (P<0.001). PMID- 11201442 TI - Effect of age of turkeys on the metabolisable energy of different foodstuffs. AB - 1. True metabolisable energy (TME) of various foodstuffs were determined in turkeys at 3, 9 and 17 weeks of age. 2. TME of soyabean meal did not change with age but TME of wheat and maize was 13% higher in 17-week-old turkeys than in 3- and 9-week-old birds. 3. These differences should be taken into account when formulating diets for turkeys. PMID- 11201443 TI - Enzymes (beta-glucanase and arabinoxylanase) and/or sepiolite supplementation and the nutritive value of maize-barley-wheat based diets for broiler chickens. AB - 1. Two experiments were conducted to study the effects of crude enzyme preparations (beta-glucanase and arabinoxylanase) and/or 20 g/kg Sepiolite (Exal) on the performance and nutrient digestion of broiler chickens fed on maize-barley wheat based diets. 2. In experiment 1, enzymes improved daily bodyweight gain (by 14%; P<0.001) and food:gain ratios (8%; P<0.001). Sepiolite improved bodyweight gain on the diets not supplemented simultaneously with enzymes (by 6% in 21-d-old chickens, P<0.05) but reduced it for enzymes-supplemeented diets. Changes in productive perfiormance with both additives were associated with changes in diet digestibility and nitrogen balance. 3. In experiment 2, enzyme supplementation reduced viscosity in jejunum and ileum and the mean retention time of digesta in the gut. Sepiolite inclusion significantly reduced the viscosity of jejunum digesta and modified the retention times of digesta in the gut, depending upon whether enzymes had been added. There was a decreased retention time without enzymes but an increase with enzyme supplementation. 4. Although different mechanisms are presumed for enzymes and sepiolite, both seem to counteract the negative effects of soluble, non-starch polysaccharides (NSP) in the diet by modifying jejunal viscosity and improving organic matter digestibility. PMID- 11201444 TI - True metabolisable energy, heat increment and net energy values of two high fibre foodstuffs in cockerels. AB - 1. The yields of true metabolisable energy (TME) and net energy (NE) from chaya leaf meal and wheatfeed were mcasured in tube-fed cockerels. 2. TME, 5.76 MJ/kg, from chava leaf meal was lower than from wheatfeed, 8.39 MJ/kg. The total heat increment attributable to the feeding of chaya leaf meal was 1-7 times greater than that of wheatfeed. 3. The net efficiency of utilisation of ME (k) from chaya leaf meal was 0.64, while that from wheatfeed was 0.86. The role of different chemical composition, especially the high fibre content of the materials, is discussed. 4. The metabolisable energy and net energy values derived from chava leaf meal represented 0.34 and 0.23 respectively of its gross energy content. The combination of lower TME and lower net efficiency of utilisation led to chaya having a NE value, 3.86 MJ/kg, which was only 0.53 that of wheatfeed. PMID- 11201445 TI - The effects of tannins on nutrient utilisation in the White Pekin duck. AB - 1. Two experiments were conducted to determine the effects of tannins on nutrient utilisation in the White Pekin duck. 2. Experiment 1 was a rapid nutrient balance assay to determine the nitrogen (N) retention and metabolisable energy (ME) of maize, low-tannin sorghum (P-954063) (Sorghum bicolor (L). Moench) and high tannin sorghum (IS-4225) cultivars for ducks. The assay lasted 120 h, with an initial 24 h food-deprivation period, a 48 h excreta collection period for endogenous losses and a 48 h excreta collection period for ingredient losses. The true metabolisable energy (TMEn) content was lower (P<0.05) in the high-tannin sorghum cultivar (13.85 MJ/kg) than the maize (14.94 MJ/kg) and the low-tannin sorghum cultivar (14.39 MJ/kg). True N retention was lower (P<0.05) for the high tannin sorghum (0.24 g) than for maize (1.33 g) and low-tannin sorghum (1.1 g). 3. In experiment 2, the brush-border membrane vesicles technique was used to determine whether tannic acid caused inhibition of L-threonine transport across duck intestinal brush-border membrane. The brush-border membrane vesicles were mixed with tannic acid solutions (pH 7.4) to give gradient tannic acid concentrations of 0, 0.05, 0.10, 0.25, 0.50, 1.00 and 2.50%. As a fraction of the control (no tannic acid), the maximal inhibition of L-threonine transport (Imax) under the sodium-gradient condition was 77.10% (P<0.05). Under the sodium-free condition, the maximal inhibition of L-threonine transport (Imax) was 45.15% (P<0.05). 4. These results demonstrated that nutrient utilisation in the White Pekin duck was lower from the high-tannin sorghum cultivar than from the low tannin sorghum cultivar. The results also suggested that the antinutritive effects of tannins in foodstuffs are due partly to their inhibitory action on intestinal brush-border bound amino acid transporter proteins. PMID- 11201447 TI - Modelling the static and dynamic responses of total heat production of broiler chickens to step changes in air temperature and light intensity. AB - 1. The objective of this work was to explore the possibilities of modelling the static and dynamic responses of total heat production of broiler chickens to step changes in temperature and light intensity (light-dark alterations) using compact dynamic model structures. 2. Seventy-seven experiments were performed in an open circuit respiration chamber to measure the dynamic response of heat production to step variations in temperature and light (on/off). The animal responses were modelled using transfer function model structures. 3. It was demonstrated that the complex process of the dynamic response of heat production of broiler chickens to step changes in air temperature and light-dark alterations can be modelled assuming 1st order dynamics. The coefficient of determination between measured and simulated heat production was on average 0.83 for responses to air temperature and 0.93 for responses to light-dark alterations. PMID- 11201446 TI - Influence of esterified-glucomannan on performance and organ morphology, serum biochemistry and haematology in broilers exposed to individual and combined mycotoxicosis (aflatoxin, ochratoxin and T-2 toxin). AB - 1. A study was conducted to evaluate the individual and combined effects of aflatoxin B1 (AF), ochratoxin A (OA) and T-2 toxin (T-2) on performance, organ morphology serum biochemistry and haematology of broiler chickens and the efficacy of esterified-glucomannan (E-GM), a cell wall derivative of Saccharomyces cerevisiae1026 in their counteraction. 2. Two dietary inclusion rates of AF (0 and 0.3 mg/kg), OA (0 and 2 mg/kg), T-2 (0 and 3 mg/kg) and E-GM (0 and 1 g/kg) were tested in a 2 x 2 x 2 x 2 factorial manner on a total of 960 broiler chickens from 1 to 35 d of age in an open sided deep litter pen house. 3. Body weight and food intake were depressed by all the mycotoxins, OA being the most toxic during early life. 4. Weights of kidney and adrenals were increased by AF and OA. Liver weight was increased by AF (17.8%), while OA increased gizzard weight (14.6%) and reduced bone ash content (8.1%). T-2 toxin showed no effect on these variables. 5. Serum cholesterol content was decreased and activity of serum gamma glutamyl transferase (GGT) was increased by AF and OA while serum protein content was decreased by AF. These effects were more pronounced at 21 d than at 35 d of age. Inconsistent responses were seen in the other variables: blood urea nitrogen (BUN) content, activities of serum alanine amino transferase and aspertate amino transferase. Blood haemoglobin content was depressed by AF and T 2, whereas blood coagulation time was prolonged by OA. 6. Significant interactions were observed between any 2 toxins for their additive effects on body weight, food intake, bone ash content and serum GGT activity at 21 d. Conversely, antagonistic interactions were observed among any 2 of the toxins for their effects on variables such as serum protein and serum cholesterol content. Simultaneous feeding of all 3 mycotoxins did not show increased toxicity above that seen with any 2. 7. Esterified-glucomannan increased body weight (2.26%) and food intake (1.6%), decreased weights of liver (32.5%) and adrenals (18.9%) and activity of serum GGT (8.7%), and increased serum protein (14.7%), cholesterol (21.9%), BUN (20.8%) and blood haemoglobin (3.1%) content, indicating its possible beneficial effect on mycotoxicosis in broiler chickens. PMID- 11201448 TI - Lack of response of laying hens to relative humidity at high ambient temperature. AB - 1. The effects of relative humidity (rh=40% to 70%) at high ambient temperature (Ta) on the performance of laying hens at different ages (8 to 10 months, Trial 1; and 16 to 18 months, Trial 2) was evaluated. Laying hens were exposed to 25 degrees C (control) for 3 weeks and thereafter acclimated for 1 week to 35 degrees C and 4 different rh. 2. Body weight declined significantly in young and older hens exposed to 60% or 70% and 70% rh, respectively: Food intake declined with increasing Ta, except in the case of older hens exposed to 60% rh, for which it remained relatively constant. Water consumption, however, increased with increasing Ta but the increase was significant in young hens exposed to 70% rh only. 3. Egg production was not affected by the changes in Ta. However, a decrease in egg production was observed in older hens exposed to 60% rh. 4. Egg weight (EW), shell weight (SW) and shell thickness (ST) were significantly reduced by exposure to elevated Ta, whereas % breakage significantly increased. In young hens, a response to rh was exhibited in ST which was significantly higher in hens exposed to the low rh (40% to 45%) than in those exposed to the highest rh (70% to 75%). 5. It can be concluded that Ta is the main environmental factor affecting young and older laying hens while the effect of rh is minor. PMID- 11201449 TI - Effects of continuous supplementations of ascorbic acid, aspirin, vitamin E and selenium on some haematological parameters and serum superoxide dismutase level in broiler chickens. AB - 1. This study was conducted using male broiler chickens to determine the effects of ascorbic acid, aspirin, ascorbic acid+aspirin, vitamin E+selenium and ascorbic acid+aspirin+vitamin E+selenium supplementations on haematological parameters and serum superoxide dismutase concentration. 2. One hundred and twenty day-old male Hubbunt broiler chicks were randomly divided into 6 experimental groups of 20 chicks each and placed in different pens. Groups 2, 3, 4, 5 and 6 were given a diet supplemented with ascorbic acid, aspirin (in water), ascorbic acid+aspirin, vitamin E+selenium and ascorbic acid+aspirin+vitamin E+selenium, respectively for 45 d while group 1 was given a commercial broiler diet. 3. There was no significant effect of ascorbic acid, aspirin, ascorbic acid+aspirin, vitamin E+selenium supplementations on any of the haematological parameters (red blood cell, haemoglobin, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin concentration, mean corpuscular haemoglobin) in broilers but ascorbic acid+aspirin+vitamin E+selenium supplementation significantly decreased the white blood cell counts. 4. In addition to this, ascorbic acid, aspirin, ascorbic acid+aspirin and ascorbic acid+aspirin+vitamin E+selenium supplementations had no significant effect on the serum superoxide dismutase level, but vitamin E+selenium supplementation increased the serum superoxide dismutase level. PMID- 11201450 TI - Seeing is believing. PMID- 11201451 TI - The National Institute of Biomedical Imaging and Bioengineering Establishment Act: an interim report. PMID- 11201452 TI - In vivo imaging of gene expression:. AB - With the ability to readily engineer genes, create knock-in and knock-out models of human disease, and replace and insert genes in clinical trials of gene therapy, it has become clear that imaging will play a critical role in these fields. Imaging is particularly helpful in recording temporal and spatial resolution of gene expression in vivo, determining vector distribution, and, ultimately, understanding endogenous gene expression during disease development. While endeavors are under way to image targets ranging from DNA to entire phenotypes in vivo, this short review focuses on in vivo imaging of gene expression with magnetic resonance and optical techniques. PMID- 11201453 TI - Statistical test to assess rank-order imaging studies. AB - RATIONALE AND OBJECTIVES: Rank-order experiments often provide a reasonable method of determining whether a large-scale receiver operating characteristic study can be justified. The authors' purpose was to formalize a proposed method for analyzing rank-order imaging experiments and provide methods that can be used in determining sample sizes for both cases and raters. MATERIALS AND METHODS: Simulations were conducted to determine the adequacy of the normal approximation of a statistic used to test the null hypothesis of random ordering. For a multireader experiment, formulas are presented and guidelines are provided to enable investigators to determine the number of required readers (raters) and cases for a specific study. RESULTS: When there are at least five ordered images per case, 10 cases are sufficient to test a random rank order. When there are only three or four images for a case, 20 cases are required. The authors constructed tables of statistical power for selected numbers of ordered images, numbers of cases, and degrees of trend, and they also provide an approximation for use in situations that are not tabled. CONCLUSION: The statistical methods for analyzing rank-order experiments and estimating sample sizes for study planning are relatively simple to implement. The derived formulas for sample size estimation, when applied to typical imaging experiments, indicate that modest numbers of cases and readers are required for rank-order studies. PMID- 11201454 TI - Journal publications in radiologic education: a review of the literature, 1987 1997. AB - RATIONALE AND OBJECTIVES: This study was designed to analyze articles on radiologic education quantitatively and qualitatively, comparing those published in 1987-1997 with those published in 1966-1986. MATERIALS AND METHODS: An initial literature search used four major databases to identify and retrieve articles related to radiologic education. Additional articles were identified through manual cross-checking of references from the original articles. All articles were reviewed by two radiologists as to type of article (editorial, expository, survey, correlational, or experimental, including preexperimental, quasi experimental, or true experimental), statistics used (inferential or descriptive), educational emphasis (medical student, resident, postgraduate, or other), and topic of article (philosophical or political, technology, program evaluation, program description, examinations, or career decisions). Interrater agreement was estimated by means of the kappa statistic. A chi2 test for independence was used to assess whether the relative distribution of articles was similar for the two periods. RESULTS: More articles per year were published in 1987-1997 (n = 12.6, P < .01) compared with 1966-1986 (n = 9.2). Articles pertinent to radiologic resident education predominated (50.7% vs 29.9% in the prior study, P < .01). In both periods, most articles were expository (37.7% vs 49.5%), and the most common topic was program description (34% vs 35%). Editorials decreased from 35.5% to 18.1%. Experimental studies accounted for 12.3%, increased from 8.7%. The fastest-growing topic of study was technology (30.4% vs 17.5%, P < .01). CONCLUSION: The increased number of articles addressing radiologic education is encouraging. Although the percentage of experimental studies increased slightly in this period, there is still little empirical research in radiologic education. PMID- 11201455 TI - Molecular imaging in vivo with PET and SPECT. PMID- 11201456 TI - T1rho imaging of murine brain tumors at 4 T. AB - RATIONALE AND OBJECTIVES: The goal of this study was to evaluate the utility of T1rho weighting in magnetic resonance imaging of murine brain tumors. MATERIALS AND METHODS: S91 Cloudman melanoma was implanted in mouse brains (n = 4). A T2 weighted spin-echo (SE) and a T1rho-weighted fast SE-based sequence were performed on a 4-T clinical imager. T2 and T1rho maps were computed. The tumor-to normal-tissue contrast was compared between T2-weighted, T1rho-weighted, proton density-weighted, and pre- and postcontrast T1-weighted SE images. RESULTS: The tumor-tissue contrast of the T1rho-weighted images was similar to that of the T2 weighted images but less than that of the postcontrast T1-weighted images. The T1rho-weighted images provided better definition of tumor boundaries than T2 weighted images. At spin-locking powers of 0.5 and 1.5 kHz, the T1rho of the tumor was 64.0 msec +/- 0.46 and 68.65 msec +/- 0.59, respectively. There was no significant inter- or intra-animal variation in T1rho for tumor or normal brain cortex. CONCLUSION: T1rho-weighted imaging performed at low spin-lock strengths qualitatively depicted tumor borders better than proton-density or T2-weighted imaging and could be useful in treatment planning when combined with other imaging sequences. PMID- 11201457 TI - Optimal electrocardiographically triggered phase for reducing motion artifact at electron-beam CT in the coronary artery. AB - RATIONALE AND OBJECTIVES: The authors performed this study to (a) investigate coronary movement with electron-beam computed tomography (CT) and (b) find the optimal electrocardiographic (ECG) triggering phase for eliminating motion artifact. MATERIALS AND METHODS: One hundred fifty-one patients without arrhythmia were examined with electron-beam CT. First, movie scans were obtained to create displacement and velocity graphs of coronary artery movement. Then, a volume scan with an exposure time of 100 msec was obtained with various ECG trigger settings. RESULTS: Movement patterns of coronary arteries varied with heart rate. Optimal triggering phase was before atrial systole (near 71% of the R R interval) when heart rate was slower than 68 beats per minute and at ventricular end systole when heart rate was fast. Rate of severe motion artifacts decreased from 43% to 0% when triggering was altered from 80% of the R-R interval to the individual optimal value. Experimental values of the optimal phase at different heart rates were derived, and severe motion artifact was only 3.0% with these values. CONCLUSION: ECG triggering set according to the heart rate enables a great reduction in motion artifacts at electron-beam CT with a 100-msec exposure time. The results may have implications for magnetic resonance imaging of the coronary artery. PMID- 11201458 TI - Quantifying the characteristics of unambiguous chest radiography reports in the context of pneumonia. AB - RATIONALE AND OBJECTIVES: The purpose of this study was to statistically identify some characteristics of unambiguous (ie, clear) chest radiography reports in the context of acute bacterial pneumonia. MATERIALS AND METHODS: Seven physicians individually read 292 chest radiography reports to determine if they contained radiologic evidence of pneumonia. Unambiguous reports were defined as those that physicians unanimously classified as supporting or not supporting the diagnosis of pneumonia. Ambiguous reports were assigned degrees of ambiguity on the basis of how much disagreement they caused among the physicians. Characteristics of unambiguous reports as described in the literature were manually quantified and assigned to every report. To identify characteristics that statistically distinguished unambiguous from ambiguous reports, the authors performed an ordinal logistic regression analysis for which the dependent variable was the number of dissenting votes the report received and the independent variables were the quantified characteristics of the report. RESULTS: Six independent variables were statistically significantly associated with unambiguous reports (P < .05). Three were positively associated: an interpretation of whether findings supported the diagnosis of pneumonia in reports with pneumonia-related observations, short sentences, and redundancy of pneumonia-related observations. Three were negatively associated: high use of uncertainty modifiers for pneumonia-related observations, use of only descriptive terms to describe pneumonia-related observations, and insufficient amount of pneumonia-related information. CONCLUSION: The most influential characteristic of an unambiguous chest radiography report was an interpretation of whether the radiograph supported the diagnosis of pneumonia when findings could be indicative. PMID- 11201459 TI - Impact of PACS on the education of radiology residents: the residents' perspective. AB - RATIONALE AND OBJECTIVES: Because digital imaging and the picture archiving and communication system (PACS) are replacing radiographic film, the effect of PACS on residents' perceptions and their educational experience was investigated. MATERIALS AND METHODS: Residents taking part in large diagnostic radiology training programs at two hospitals were surveyed. Approximately 75% of radiographic studies were reviewed with the use of PACS at both hospitals. Survey topics included technical and didactic issues based on direct and indirect comparison with analog (conventional film) images. RESULTS: Fifty residents were polled (20 respondents). The majority has been using PACS for more than 1 year (14 of 20, 70%) to interpret 75%-100% of cases (11 of 20, 55%). The majority believed that PACS improved patient care (15 of 20, 75%) and their educational experience (15 of 20, 75%). A minority believed that increased patient throughput was harmful to the educational experience (five of 20, 25%) because it permitted attending radiologists to review cases too quickly (four of 20, 20%). Residents favored PACS over hard-copy images for ease of manipulation, resolution, and ability to see pathologic conditions and normal anatomic characteristics. CONCLUSION: Residents believe that PACS has positively affected their learning experience and does not negatively affect the quality of resident education. PMID- 11201460 TI - Clinical competence assessment in radiology: introduction of an objective structured clinical examination in the medical school curriculum. AB - RATIONALE AND OBJECTIVES: Traditional oral and written examinations can be limited in predicting future clinical performance. Therefore Objective Structured Clinical Examinations (OSCEs) have been introduced in other specialties. The authors assessed their value in radiology. MATERIALS AND METHODS: The study includes 122 Harvard medical students who undertook 1-month compulsory clerkships at one of three hospitals (A, B, or C) in their 3rd and 4th year and a compulsory OSCE in their 4th year. The OSCE was constructed from five cases. Each had eight or nine standardized questions designed to test, within a set time, the perception of essential findings, their interpretation, and clinical judgment (maximum possible score, 100). Clerkship grades were high honors (score of 3), honors (score of 2), satisfactory (score of 1), and fail (score of 0). Predictors of OSCE scores-clerkship grade and affiliated hospital-were modeled as linear functions. Time elapsed between clerkship and OSCE was modeled as a nonlinear function. RESULTS: Although there was a positive relation between clerkship grade and OSCE grade, it accounted for an increase of only 5.7% in OSCE score per clerkship grade and did not predict performance of individual students. Students who trained in hospital B showed significantly higher OSCE grades. OSCE scores were highest when the examination was taken 8 months after the clerkship. CONCLUSION: The OSCE may be useful to uncover deficits in individuals and groups beyond the ones detected with traditional clerkship evaluations and provide guidance for remediation. The improved performance after additional clinical exposure suggests that the OSCE may be well suited to test the integration of radiologic and clinical knowledge. PMID- 11201461 TI - Why is ethics needed in the radiology curriculum? PMID- 11201462 TI - A3CR2 problem-solving session 2000: the teaching curriculum and the problem attending radiologist. American Association of Academic Chief Residents in Radiology. PMID- 11201463 TI - Feasibility and profitability of a radiology department providing trauma US as part of a trauma alert team. AB - RATIONALE AND OBJECTIVES: The purpose of this study was to assess the feasibility and profitability of a radiology department providing a six-point trauma ultrasound (US) examination for abdominal or pelvic free fluid as part of a trauma alert team. MATERIALS AND METHODS: The study included 191 trauma alerts, which generated 156 US examinations. A radiologist and a departmental technologist carried beepers and responded to level I and II traumas. A departmental secretary or technologist recorded when the responding technologist exited and re-entered the department and if US was performed. If performed, the US examination evaluated the four abdominal and pelvic quadrants and the suprapubic and subxiphoid regions. For 64 patients, the responding technologist recorded the times of the trauma alert, emergency room arrival, US start and finish, and return to the radiology department. RESULTS: Median response, wait, scan duration, and return times were 2, 8, 5, and 7 minutes, respectively. Median costs for the technician, physician, archiving, transcription, and equipment were $8.17, $30.85, $0.97, $4.80, and $41.22, respectively. Reimbursement per examination averaged $110.60. Sensitivity analyses that varied the time spent (median vs mean), US non-use rate (10%-18%), and years of depreciation (5-7 years) yielded net results ranging from a $36.60 profit to a $6.12 loss per examination. CONCLUSION: A radiology department can profitably respond to trauma alerts and provide a six-point trauma US examination for free fluid. PMID- 11201464 TI - Malignant lymphoma of the central nervous system with delayed increased accumulation on I-123 IMP SPECT. AB - Ga-67 citrate scintigraphy in the management of malignant lymphomas is well established. It cannot, however, differentiate malignant from benign lesions because this agent also accumulates in benign inflammatory lesions. The authors present a case of increased I-123 IMP uptake on both early and delayed SPECT images in a patient with malignant lymphoma of the central nervous system. Results show that I-123 IMP SPECT can help differentiate malignant lymphoma from benign lesions and other malignant brain tumors. PMID- 11201465 TI - Clearance of Tc-99m DTPA aerosol in mismatched and matched pulmonary perfusion defects. AB - PURPOSE: To evaluate clearance changes of Tc-99m DTPA aerosol in mismatched and matched pulmonary perfusion defects. MATERIALS AND METHODS: Twenty-one patients (14 women, 7 men; mean age, 51 +/- 14 years) with possible pulmonary embolism were included in the study. On the day after perfusion (Q) scintigraphy with 5 mCi Tc-99m MAA, radioaerosol inhalation scintigraphy was performed using 45 mCi Tc-99m DTPA. Immediately and 45 minutes after the inhalation, early and delayed inhalation images (EI and DI, respectively) were obtained. Group 1 included 11 patients with mismatched defects who had a high probability of pulmonary embolism according to the Q/EI scan results. Group 2 included 10 patients with matched defects who had a low probability of PE. Contralateral normal lungs of 7 patients in group 2 served as controls (group 3). In groups 1 and 2, regions of interest were drawn over the mismatched and matched perfusion defects where they were best visualized, and this region of interest was mirrored to the same region on EI and DI images. For the control group, this was done in the contralateral normal lung. Mean counts in each region of interest were used for quantitative analysis, and the percentage clearance ratio was calculated using the following formula: early counts - late counts/early counts x 100. RESULTS: The average percentage clearances for the three groups were as follows: group 1, 37% +/- 10%; group 2, 21% +/- 4%; group 3, 24% +/- 7%. Differences between groups 1 and 3 were significant, as were those between groups 1 and 2 (P < 0.05). Patients with mismatched perfusion defects had increased DTPA clearance compared with the control group and those with matched defects. CONCLUSIONS: Vascular occlusion may lead to impairment of the alveolar-capillary barrier and consequently an increase in the clearance of Tc-99m DTPA aerosol in embolized regions. Immediately after inhalation, Tc-99m DTPA imaging should be started in the projection where perfusion defects are best seen to avoid potential misinterpretation of pulmonary embolism. PMID- 11201466 TI - Radionuclide cisternography in spontaneous intracranial hypotension with simultaneous leaks at the cervicothoracic and lumbar levels. AB - This case report clearly illustrates defined simultaneous cerebrospinal fluid leaks at the cervicothoracic and upper lumbar areas. A 53-year-old woman without a remarkable medical history was hospitalized for sudden onset of severe headache. The headache lasted more than 1 week and standing or sitting positions exaggerated the symptoms, although it was relieved when the patient was recumbent. Radionuclide cisternography was performed using 150 MBq (4 mCi) Tc-99m DTPA. It revealed two cerebrospinal fluid leaks from the cervicothoracic junction bilaterally and the left side of the upper lumbar area. Epidural blood patching was tried at the lumbar level (L1-L2) and showed only a transient effect. A second trial of this method at the level of C7-T1 performed 2 days later resulted in immediate improvement of the symptoms without recurrence. The simultaneous cerebrospinal fluid leaks were detected successfully with radionuclide cisternography using Tc-99m DTPA, which provided a useful guideline for treatment despite the limitations of delayed scanning. PMID- 11201467 TI - Bone scintigraphy in testicular tumors. AB - PURPOSE: Testicular tumors do not occur frequently. Primary treatment is surgical, and radiotherapy and chemotherapy can play important roles in cases of metastatic disease. Bone scintigraphy is used largely for early detection of skeletal metastases from several tumors, and conventional radiographic studies are less sensitive than the nuclear technique for such a purpose. The aim of this study was to identify the role of bone scintigraphy in cases of testicular tumors, regardless of the grade. MATERIALS AND METHODS: The authors examined 28 patients (8 to 52 years old) with proved testicular tumors using Tc-99m MDP (750 MBq; 20 mCi) injected intravenously. Whole-body images were obtained 2 hours later, at 500,000 counts per image. Radiographic studies were obtained to investigate abnormal areas noted on scintigraphy. RESULTS: The results of bone scintigraphy were abnormal in seven cases, consisting of variable but diffuse uptake in the iliac bone on the same side as the affected testicle. MDP uptake was substantial in five of these patients (four seminomas, one nonseminoma; only two radiographic studies were abnormal), and the two other patients had moderate uptake of the radiopharmaceutical (two seminomas; radiographic studies were normal). Metastases were confirmed by biopsy in three cases. DISCUSSION: Early metastases from seminomas can occur through the lymphatic drainage toward the iliac lymph node chain. This could explain these findings. The scintigraphic aspects of the affected iliac bones seem characteristic. CONCLUSIONS: Early detection of metastases is very important to ensure the efficacy of radiotherapy and chemotherapy. Bone scintigraphy may play an important role in such cases and seems to be more sensitive than conventional radiography. Testicular tumor metastases should be considered when iliac involvement is observed. Paget's disease should be included in a differential diagnosis. PMID- 11201468 TI - TI-201 SPECT compared with histopathologic grade in the prognostic assessment of cerebral gliomas. AB - PURPOSE: Although TI-201 SPECT has been used to evaluate the malignant grade of cerebral gliomas, the gold standard continues to be histopathologic examination. The authors assessed and compared the prognostic abilities of the two studies using survival analysis. MATERIALS AND METHODS: Twenty-nine patients underwent 34 sessions of TI-201 SPECT plus surgery for primary or recurrent cerebral gliomas 12 to 78 months before this analysis. Using conventional survival analyses, such as the log-rank test, Cox regression, and the Akaike cross-tab method, the authors evaluated the prognostic significance of 10 variables: histopathologic grade, TI-201 SPECT, Tc-99m HMPAO SPECT, tumor cell viability, radionecrosis, neurologic defects, clinical improvement, surgery, chemotherapy, and external beam radiotherapy. RESULTS: TI-201 SPECT was most strongly related to prognosis, followed by histopathologic grade. The other variables had little prognostic value. The Cox stepwise selection procedure indicated that TI-201 SPECT was the only independent predictor of outcome, whereas histopathologic analysis was eliminated from the prognostic model. However, the Kaplan-Meier survival curve and the Akaike method indicated that histopathologically low-grade tumors were more closely associated with longer-term survival than were TI-201 low uptake tumors. CONCLUSIONS: TI-201 SPECT is not only closely correlated with the histopathologic grade of tumor but is a significantly better predictor of outcome than histopathologic grade. However, histopathologic examination may provide additional information on longer-term survival. TI-201 SPECT is a valuable procedure, especially in patients in whom a histologic diagnosis of possible glioma cannot be made. PMID- 11201469 TI - Brain SPECT used to evaluate vasospasm after subarachnoid hemorrhage: correlation with angiography and transcranial Doppler. AB - PURPOSE: The primary objective of this study was to correlate Tc-99m HMPAO and ethyl cysteine dimer perfusion brain SPECT imaging with angiography and transcranial Doppler (TCD) to identify vasospasm after subarachnoid hemorrhage. METHODS: A retrospective analysis of consecutive patients who had cerebral blood flow SPECT imaging for subarachnoid hemorrhage and aneurysm clipping was made. Flow velocity measurements were correlated using TCD and cerebrovascular angiography. RESULTS: Of the 129 patients were included in this study, 84 were female and 45 were male, with a mean age of 51.9 years and a median age of 51 years (range, 9 to 84 years). Eighty-nine patients had brain SPECT evidence of hypoperfusion. Concordance was found between SPECT and TCD with vasospasm in 57 of 89 (64%) patients and nonconcordance was evident in 32 patients (36%). Eleven patients who had concordance between SPECT and TCD had nonconcordant results of angiography for vasospasm. CONCLUSIONS: These findings suggest that all three methods are complementary to each other in the evaluation of patients with vasospasm after subarachnoid hemorrhage. Concordance of 64% between SPECT and TCD is acceptable and explicable by the differences in technique and measurement of cerebral blood flow compared with vascular narrowing, respectively. PMID- 11201470 TI - Evaluation of recurrent squamous cell carcinoma of the head and neck with FDG positron emission tomography. AB - PURPOSE: This study compared the effectiveness of fluorodeoxyglucose (FDG) positron emission tomography (PET) with computed tomography (CT), magnetic resonance imaging (MRI), or both for the assessment of recurrent squamous cell carcinoma of the head and neck. The value of quantifying the standardized uptake values (SUV) to distinguish recurrent neoplasm from inflammatory lesions and normal structures was also evaluated. METHODS: Forty-three patients with head and neck cancer were examined with F-18 FDG PET at least 4 months after their last course of radiation therapy (mean, 11 months). The SUVs were measured in visually identified regions of abnormally increased activity and were compared with the values in normal mucosa, the base of the tongue, and the hard palate to determine if an optimal cutoff value exists for diagnosing recurrence of malignant lesions. The final diagnosis of recurrence was made based on biopsy or at least 6 months' clinical follow-up. RESULTS: FDG PET correctly detected recurrence in 20 of 22 patients who had 45 discrete lesions located in the field of the upper aerodigestive tract. Two false-negative and three false-positive results were identified. The accuracy of FDG PET was 88% (38 of 43 patients), compared with 66% (25 of 38 patients) for CT, MRI, or both. Although there was a significant difference of SUVs (P = 0.0036) between the recurrent lesions and normal structures, the optimal cutoff values were difficult to define. CONCLUSIONS: Visual analysis of FDG PET is significantly more accurate in the diagnosis of recurrent squamous cell cancer of the head and neck than are CT or MRI. However, single SUV quantification does not significantly enhance efficacy. PMID- 11201471 TI - Unilateral proptosis with thyrotoxicosis resulting from solitary retroorbital soft tissue metastasis from follicular carcinoma thyroid. AB - Unilateral proptosis can be of neoplastic origin, even if the results of thyroid function tests suggest hyperthyroid disease, and it needs proper investigation with a computed tomographic scan of the orbit. The authors present a case of left sided proptosis resulting from a metastasis in the retroorbital soft tissue from follicular carcinoma of the thyroid. A nodular goiter involving the left lobe and isthmus was found. The initial thyroid function test values suggested hyperthyroid disease and the patient had clinical signs of toxicity. A computed tomographic scan of the orbit revealed a left-sided retroorbital soft tissue mass, part of which was resected and found be to a metastasis from follicular carcinoma of thyroid. Total thyroidectomy was performed and the patient was treated with I-131 after operation. The proptosis resolved with I-131 treatment. PMID- 11201473 TI - Focal intrasplenic extramedullary hematopoiesis mimicking lymphoma: diagnosis made using liver-spleen scintigraphy. PMID- 11201472 TI - Role of Tc-99m sestamibi scintigraphy in the diagnosis and surgical decision making process in primary hyperparathyroid disease. AB - PURPOSE: Ultrasound (US) and scintigraphy are used most frequently of all the available imaging techniques for the preoperative evaluation of patients with possible primary hyperparathyroid disease. The aim of this study was to assess the value of dual-phase Tc-99m MIBI scintigraphy compared with US in the detection of adenomatous or hyperplastic glands and in the surgical decision making process for patients with a biochemical diagnosis of primary hyperparathyroid disease. METHODS: Ninety-seven patients with increased levels of parathyroid hormone and calcium, and at least 6 months' follow-up after US and scintigraphy, were examined retrospectively to assess the influence of the diagnostic work-up on the therapeutic decision of the referring clinicians and to evaluate the sensitivity of these diagnostic tools in the surgically treated patients. Forty-eight patients underwent surgery. RESULTS: Parathyroid adenomas were found in 43 patients and hyperplasia in 1, whereas 4 patients had no evidence at surgery. The sensitivity and specificity rates were 84.4% and 95.9% for scintigraphy, and 66.6% and 98.6% for US, respectively. Of the 49 nonsurgically treated patients, 35 had negative results with both MIBI and US; only 3 had positive findings with both imaging methods. Patients treated conservatively had significantly lower parathyroid hormone and serum calcium levels than did the patients who had surgery. CONCLUSIONS: The data suggest that the high sensitivity of dual-phase MIBI scintigraphy can improve the detection of hyperfunctioning parathyroid glands. Furthermore, despite the controversy surrounding the use of imaging methods in the preoperative assessment of primary hyperparathyroid disease, these data suggest that the decision of the clinician to order surgery for a patient with a moderate increase of serum PTH level may be influenced by the results of the imaging methods. PMID- 11201474 TI - Misleading thoracic Ga-67 uptake caused by splenic displacement. PMID- 11201475 TI - Avid Ga-67 uptake in a breast metastasis from cancer of the tongue. PMID- 11201476 TI - Biliary-colonic fistula diagnosed via hepatobiliary scintigraphy. PMID- 11201477 TI - Hepatobiliary scintigraphy showing acute complete common bile duct obstruction in a patient with acute hepatitis. PMID- 11201478 TI - Acquired hourglass gallbladder. PMID- 11201479 TI - Intra-arterial Tc-99m MDP injection mimicking reflex sympathetic dystrophy. PMID- 11201480 TI - Thoracic lymph node visualization after a peritoneal leak study. PMID- 11201481 TI - Esophageal inflammation evident on oral Tc-99m sulfur colloid gastroesophageal imaging. PMID- 11201482 TI - Unusual depression and Tc-99m ethyl cysteinate dimer SPECT brain uptake. PMID- 11201483 TI - Damaged ureter detected on a bone scan. PMID- 11201484 TI - Scintigraphic findings of dysplasia epiphysealis hemimelica: a case report. PMID- 11201485 TI - Isolated lower extremity I-131 bone marrow uptake in a runner. PMID- 11201486 TI - Liver uptake and increased renal uptake of Tc-99m HMDP in a patient with iron overload. PMID- 11201487 TI - Extensive bone infarct in myeloid leukemia correlation of bone scan and magnetic resonance imaging. PMID- 11201488 TI - Discrepancy between clinical symptoms and Tc-99m MDP bone scan findings before and after strontium-89 therapy for metastatic bone pain of prostate carcinoma. PMID- 11201489 TI - Radionuclide venography in inferior vena cava and iliofemoral vein obstruction. PMID- 11201490 TI - An unexpected pericardial effusion. PMID- 11201491 TI - Bilateral adrenal metastases simulating abnormal renal uptake on a Ga-67 scan. PMID- 11201492 TI - I-131 iodonorcholesterol uptake in adrenal hemangioma. PMID- 11201493 TI - Current readings in nuclear medicine. PMID- 11201494 TI - Tc-99m HMPAO white blood cell scintigraphy in the assessment of the extent and severity of an acute exacerbation of ulcerative colitis. AB - PURPOSE: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with frequent exacerbations, including the risk for toxic megacolon and severe complications. In very active disease, colonoscopy should not be performed to assess the severity and the extent of the disease. The aim of the current study was to determine whether Tc-99m HMPAO-labeled white blood cell (WBC) scintigraphy can be used as an alternative to colonoscopy to determine the extent and the severity of the disease in critically ill patients. METHODS: Twenty consecutive patients (7 women, 13 men; age 38.1 +/- 13.1 years) who had a severe attack of UC underwent scintigraphy on the day of admission. Leukocytes were labeled with 200 MBq (5.35 mCi) Tc-99m HMPAO. Planar anterior and posterior imaging of the abdomen was performed 45 and 120 minutes after WBC reinjection. The tracer uptake in the different colon segments was scored visually compared with bone marrow uptake. A symptom score was made and C-reactive protein was measured as a serologic marker of inflammation. Rectosigmoidoscopy with biopsy was performed within 24 hours of scintigraphy. Scintigraphic, endoscopic, and histologic results were compared for disease activity. RESULTS: The mean symptom score was 12.7 (+/-0.7) on a scale of 21, and mean the C-reactive protein level was 6.8 (+/-1.2) mg/l. No significant difference was found between the scintigraphic score of the rectum and the endoscopic or the histologic score. The best correlation was found with the latter (r = 0.66, P < 0.01). Based on the results of scintigraphy, disease involved the left side of the colon up to the splenic flexure in 10 patients. The other patients had pancolitis. CONCLUSIONS: Disease severity can be determined adequately by planar WBC scintigraphy in patients with severe attacks of UC. Because the presence and severity of disease correlates well with endoscopic and histologic findings, WBC scintigraphy can assess disease extent without the need for colonoscopy. This decreases the number and severity of complications that can occur in already critically ill patients. PMID- 11201495 TI - Interactions between effects of adrenalectomy and diet on insulin secretion in fa/fa Zucker rats. AB - Our objective was to determine if a cafeteria-type diet with increased fat content would block the decrease in insulin secretion induced by adrenalectomy in obese rats. Five week old Zucker (fa/fa) rats were adrenalectomized. One week later, half of the adrenalectomized groups, and age-matched, sham-operated animals were given a diet of 16% fat and 44% carbohydrate. Control animals were maintained on standard rat chow (4.6% fat and 49% carbohydrate). After 4 weeks on the diets, in vivo measurements included caloric intake, weight gain, plasma corticosterone, triglyceride, free fatty acids, and oral glucose tolerance tests. In vitro measurements included glucose-stimulated insulin secretion, glucose phosphorylating activity, islet triglyceride content, and fatty acid oxidizing activity of cultured islets. Generally, the cafeteria diet did not block the effects of adrenalectomy on in vitro insulin secretion parameters, even though in sham-operated animals weight gain and insulin resistance was induced by the diet in vivo. Adrenalectomy and the diet exerted independent effects on glucose phosphorylation and fatty acid oxidation in islets. In conclusion, adrenalectomy decreased the elevated insulin secretion in fa/fa rats. The failure of a cafeteria diet enriched in fat to block the adrenalectomy-mediated changes in B cell function indicates the importance of glucocorticoids and centrally-mediated effects on insulin secretion and other metabolic parameters. PMID- 11201496 TI - Effect of autonomic neurotransmitters on excitable gap composition in canine atrial flutter. AB - Atrial arrhythmias are believed to be influenced by autonomic nervous system tone. We evaluated the effects of sympathetic and parasympathetic activation on atrial flutter (AF1) by determining the effects of norepinephrine (NE) and acetylcholine (ACh) on the composition of the excitable gap. A model of reentry around the tricuspid valve was produced in 17 chloralose anesthetized dogs using a Y-shaped lesion in the intercaval area that extended to the right atrial appendage. Excitable gap characteristics were determined during AF1 by scanning diastole with a single premature extrastimulus at progressively shorter coupling intervals to define the reset-response curve. Measurements were made during a constant infusion of NE (15 microg/min) into the right coronary artery and repeated during ACh infusion (2 microg/min) following a 15 min recovery period. The excitable gap (27 +/- 1 ms) was significantly (P < 0.001) increased by NE (34 +/- 1 ms) and ACh (50 +/- 2 ms). The fully excitable portion (7 +/- 1 ms) was also significantly (P < 0.001) increased by NE (17 +/- 1 ms) and ACh (43 +/- 2 ms). We conclude that both neurotransmitters increase the safety margin of full excitability ahead of the wavefront, demonstrating that parasympathetic and sympathetic activation can facilitate the persistence of this refractory atrial arrhythmia. PMID- 11201497 TI - Perturbation of rat renal tubule transport of the organic cation amantadine in recent onset streptozotocin-induced diabetes and in uninephrectomy. AB - The effects of early-stage diabetes mellitus and uninephrectomy on the renal tubule transport of amantadine were investigated. Kidney tubules were isolated from streptozotocin-induced diabetic (+/- insulin treatment) uninephrectomized, and control male Sprague-Dawley rats. There were no differences in the Km of amantadine uptake in renal proximal and distal tubules for the imposed treatments compared with control values. Vmax for amantadine uptake in the proximal tubules of diabetic and uninephrectomized rats was higher than the respective control (P < 0.05). Vmax for insulin-treated diabetic rats was similar to control values but was lower than that for untreated diabetic rats (P < 0.05). Vmax for distal tubule uptake was not altered by any treatment. Structure-activity studies demonstrated that bicarbonate-dependent amantadine uptake was inhibited by glycolate and lactate, but not by propionate or alpha-, beta-, or gamma hydroxybutyrate. Early stage streptozotocin-induced diabetes mellitus and uninephrectomy induced changes in the kidney that resulted in a similar selective increase in proximal tubule amantadine uptake. These data represent the first description that experimentally induced diabetes mellitus and uninephrectomy modulate the function of the renal tubule organic cation (amantadine) transport system. Both interventions represent potential models in which phenotypic modulation of the renal elimination of organic cationic drugs may be achieved and studied. PMID- 11201498 TI - The mechanisms of the vulnerable window: the role of virtual electrodes and shock polarity. AB - Vulnerability and defibrillation are mechanistically dependent upon shock strength, polarity, and timing. We have recently demonstrated that shock-induced virtual electrode polarization (VEP) may induce reentry. However, it remains unclear how the VEP mechanism may explain the vulnerable window and polarity dependence of vulnerability. We used a potentiometric dye and optical mapping to assess the anterior epicardial electrical activity of Langendorff-perfused rabbit hearts (n = 7) during monophasic shocks (+/-100 V and +/-200 V, duration of 8 ms) applied from a transvenous defibrillation lead at various coupling intervals. Arrhythmias were induced in a coupling interval and shock polarity dependent manner: (i) anodal and cathodal shocks induced arrhythmias in 33.2 +/- 30.1% and 53.1 +/- 39.3% cases (P < 0.01), respectively, and (ii) the vulnerable window was located near the T-wave. Optical maps revealed that VEP was also modulated by the coupling interval and shock polarity. Recovery of excitability produced by negative polarization, known as de-excitation, and the resulting reentry was more readily achieved during the relative refractory period than the absolute refractory period. Furthermore, anodal shocks produced wavefronts propagating in an inward direction with respect to the electrode, whereas cathodal shocks propagated in an outward direction. Wavefronts produced by anodal shocks were more likely to collide and annihilate each other than those caused by cathodal shocks. The probability of degeneration of the VEP-induced phase singularity into a sustained arrhythmia depends upon the gradient of VEP and the direction of the VEP-induced wavefront. The VEP gradient depends upon the coupling interval, while the direction depends upon shock polarity; these factors explain the vulnerable window and polarity-dependence of vulnerability, respectively. PMID- 11201500 TI - YC-1 enhances the responsiveness of tolerant vascular smooth muscle to glyceryl trinitrate. AB - A major limitation of the use of organic nitrates in cardiovascular medicine is the development of tolerance, which has been attributed, in part, to a decrease in their metabolic activation in the vascular smooth muscle cell. Recently, 3-(5' hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) was shown to potentiate vascular smooth muscle responsiveness to glyceryl trinitrate (GTN), sodium nitroprusside, and the nitric oxide donor NOC 18, in organic nitrate-naive vascular smooth muscle. We used GTN-tolerant rabbit aortic rings (RARs) to test the hypothesis that a non-vasorelaxant concentration of YC-1 enhances the ability of the prototypical organic nitrate GTN to relax vascular smooth muscle and elevate intravascular cGMP under conditions of GTN tolerance. Treatment with YC-1 (3 microM) produced a left shift of the GTN concentration-response curve and decreased the EC50 value for GTN-induced relaxation in both GTN-tolerant and non tolerant RARs (P < 0.05). Intravascular cGMP elevation induced by GTN was enhanced in the presence of YC-1 in GTN-tolerant and non-tolerant RARs (P < 0.05). These observations indicate that YC-1, or similarly acting drugs, may be useful in overcoming the tolerance that develops during sustained GTN therapy, and that its mechanism may involve enhanced cGMP formation. PMID- 11201499 TI - Muscarinic activation of transient inward current and contraction in canine colon circular smooth muscle cells. AB - Muscarinic receptor mediated membrane currents and contractions were studied in isolated canine colon circular smooth muscle cells. Carbachol (10(-5) M) evoked a slow transient inward current that was superimposed by a transient outward current at holding potentials greater than -50 mV. Carbachol contracted the cells by 70 +/- 2%. The effects of carbachol were blocked by atropine (10(-6) M), tetraethyl ammonium (20 mM), and BAPTA-AM (25 mM applied for 20 min). The inward current and contraction were not sensitive to diltiazem (10(-5) M), nitrendipine (3 x 10(-7) M), niflumic acid (10(-5) M), or N-phenylanthranilic acid (10(-4) M), but were gradually inhibited after repetitive stimulations in Ca2+ free solution. Ni2+ (2 mM) inhibited the inward current by 67 +/- 4%. The inward current reversed at +15 mV. The outward component could be selectively inhibited by iberiotoxin (20 nM) or by intracellular Cs+. Repeated stimulation in the presence of cyclopiazonic acid (CPA, 3 microM) inhibited the carbachol-induced outward current and partially inhibited contraction. CPA did not inhibit the inward current. In conclusion, muscarinic receptor stimulation evoked a CPA-sensitive calcium release that caused contraction and a CPA-insensitive transient inward current was activated that is primarily carried by Ca2+ ions and is sensitive to Ni2+. PMID- 11201501 TI - Effect of temperature on post-tetanic potentiation in human dorsiflexor muscles. AB - The effect of temperature on post-tetanic potentiation (PTP) has been examined in the muscles of small mammals but not in human skeletal muscle. We examined PTP in the ankle dorsiflexor muscles of 10 young men by evoking twitches before and after a 7-second tetanus at 100 Hz in a control (room air approximately 21 degrees C) condition and after immersion of the lower leg in warm (45 degrees C) and cold (10 degrees C) water baths for 30 min. Exposure to cold decreased tetanus and pre-tetanus twitch peak torque, but increased rise time, half relaxation time, and muscle action potential (M-wave) amplitude; exposure to warm water had little effect. PTP was smallest in cold exposure 5 s post-tetanus, but persisted throughout the 12 min test period, whereas PTP had subsided by 6 min post-tetanus in control and warm exposures. M-wave amplitude initially decreased after exposure to warm water, recovered, then decreased again by 11 min post tetanus. In contrast, exposure to cold had no initial effect but did increase the M-wave amplitude during the last half of the 12 min test period, similar to that seen in the control. The greatest immediate decrease in rise time and half relaxation time was observed in the control; however, by 12 min post-tetanus warm exposure showed the greatest increase in rise time and half-relaxation time above pre-tetanus values. The decrease in the unpotentiated twitch torque with cooling in human dorsiflexors is typical for muscles with a predominance of type I (slow) fibres. The effect of cold on PTP is similar to that seen previously in mammalian muscles with a predominance of type II (fast) fibres, although the underlying mechanism of the cooling effect appears to differ. PMID- 11201502 TI - Uptake properties of lamivudine (3TC) by a continuous renal epithelial cell line. AB - The purpose of this study was to characterize the renal uptake properties of the cytidine analog and antiretroviral agent 3TC. The uptake of radiolabelled 3TC was measured at 37 degrees C in a continuous porcine renal epithelial cell line (i.e., LLC-PK1 cells) grown as a monolayer on an impermeable support. 3TC (5 microM) uptake (37 degrees C) by the monolayer cells was saturable (Km = 1.2 +/- 0.2 mM) but not significantly altered by various dideoxynucleoside analog drugs, nucleosides, and nucleoside transport inhibitors, suggesting that a nucleoside transporter is not involved in 3TC uptake. A number of endogenous organic cation probes and inhibitors significantly reduced 3TC uptake by the monolayer cells. Quinine, trimethoprim (TMP), and tetraethylammonium (TEA) inhibited 3TC uptake in a dose dependent manner with IC50 values of 0.6 mM, 0.63 mM, and 1.9 mM, respectively. In turn, the uptake of the typical organic cation substrate TEA was inhibited by high concentrations of 3TC. An outwardly directed proton gradient significantly increased the uptake of 3TC by the monolayer cells, suggesting the involvement of a proton exchange process. Conversely, in the presence of monensin, a Na+/H+ ionophore, the uptake of 3TC was significantly reduced. These results suggest that the uptake of 3TC by a cultured renal epithelium may be mediated by an organic cation-proton exchanger. The observed clinical interaction between 3TC and trimethoprim may be explained by competition for a common renal organic cation tubular transporter. PMID- 11201503 TI - Effect of transient stretch on intracellular Ca2+ during triggered propagated contractions in intact trabeculae. AB - Transient stretch of cardiac muscle during a twitch contraction may dissociate Ca2+ from myofilaments into the cytosol at the moment of quick release of the muscle. We studied the effect of stretch and quick release of trabeculae on changes in intracellular Ca2+ ([Ca2+]i) during triggered propagated contractions (TPCs). Trabeculae were dissected from the right ventricle of 9 rat hearts. [Ca2+]i was measured using electrophoretically injected fura-2. Force was measured using a silicon strain gauge and sarcomere length was measured using laser diffraction techniques. Reproducible TPCs (n = 13) were induced by trains of electrical stimuli (378 +/- 19 ms interval) for 7.5 s at [Ca2+]o of 2.0 mM (27.9 +/- 0.2 degrees C). The latency of the TPC force and the underlying increase in [Ca2+]i was calculated from the time (TimeF) between the last stimulus and the peak of TPC force (PeakF), or the time (TimeCa) between the last stimulus and the peak of the increase in [Ca2+]i during the TPCs (PeakCa). As a result of a 10% increase in muscle length for 150-200 ms during the last stimulated twitches, TimeF and TimeCa decreased and PeakF and PeakCa increased significantly (n = 13). In addition, transient stretch sometimes induced a twitch contraction subsequent to the accelerated TPC and its underlying increase in [Ca2+]i. These results suggest that Ca2+ binding and dissociation from the myofilaments by the stretch and quick release of muscle may modulate the TPC force and the underlying increases in [Ca2+]i and play an important role in the induction of arrhythmias. PMID- 11201504 TI - Damage induced arrhythmias: mechanisms and implications. AB - Little is known about the role played by non-uniform myocardial stress and strain distributions and by non-uniform excitation contraction coupling in mechanisms underlying the premature beats that initiate an arrhythmia. We will review the evidence in support of a mechanism in which both non-uniform contraction and increased Ca2+ load of cells adjacent to acutely damaged cells are essential in the "spontaneous" generation of Ca2+ transients during the relaxation phase of the electrically driven twitch. The putative mechanism of initiation of the propagating Ca2+ waves involves feedback of rapid length (or force) changes to dissociation of Ca2+ from the contractile filaments. A novel aspect of this concept is that these mechanically elicited Ca2+ transients induce propagating Ca2+ waves that travel into the adjacent normal myocardium and cause after depolarizations, which, in turn, may cause premature action potentials. These premature action potentials will further load the cells with Ca2+, which promotes the subsequent generation of propagating Ca2+ transients and leads to triggered arrhythmias. The damage-induced premature beats may also initiate re-entry arrhythmias in non-uniform myocardium. These observations strongly support the concept that abnormal cellular Ca2+ transport plays a crucial role in the initiation of arrhythmias in damaged and non-uniform myocardium. PMID- 11201505 TI - Evidence for the binding of beta-adrenoceptor blockers to microsomal Na+/K+ ATPase in guinea pig heart preparations. AB - We reported in a previous study that beta-adrenoceptor blockers inhibit the Mg2+ dependent ATP-hydrolytic function of Na+/K+-ATPase. To determine if this action is a result of binding of beta-blockers to the receptor sites that bind the digitalis glycosides, we performed displacement binding assays of eight beta blockers with [3H]-ouabain (OUA) in guinea pig myocardial microsomal preparations. In the first series of experiments, 10-200 microM of the beta blockers were displaced with 250 nM OUA. In the second set of experiments, 10-500 nM of OUA was displaced using 200 microM of the beta-blockers. The drugs showed concentration-dependent receptor occupancy at the different OUA levels. Propranolol (PPN), metoprolol (MTP), and sotalol (STL) showed the strongest binding; nadolol (NDL), indenolol (IDN), and atenolol (ATN) had intermediate binding; carazolol (CRZ) and celiprolol (CLP) had the weakest binding properties. The results suggest that beta-blockers may compete for the same binding sites with ouabain in their inhibition of the Na+/K+-ATPase. These actions may contribute to the mechanism for some of their cardiac effects, especially their proarrhythmic and arrhythmogenic actions. PMID- 11201506 TI - Spread of Ca2+ in the sarcomere during fast and slow activation of mammalian cardiac myocytes. AB - A multi-compartment model was used to estimate Ca2+ gradients in a sarcomere of a cardiac myocyte. The mathematical model assumed Ca2+ release from the sarcoplasmic reticulum as a driving function, and calculated Ca2+ binding to myoplasmic buffers, Ca2+ uptake by the sarcoplasmic reticulum, and diffusion of Ca2+ (and the buffers). During the fast Ca2+ transient similar to those observed during a twitch, the model predicted a large Ca2+ gradient in the sarcomere. A trajectory of the instantaneous relation between spatially averaged concentrations of Ca2+ and the Ca2+-troponin complex showed a counterclockwise loop, indicating non-equilibrium Ca2+ binding to troponin. During slow changes in [Ca2+] with time to peaks of approximately 500 ms or longer, the gradient of [Ca2+] was largely dissipated and the apparent equilibrium of the Ca2+-troponin binding reaction was suggested with little hysteresis of the trajectory. We conclude that a steady-state relation between [Ca2+] and mechanical activity can be achieved uniformly in the sarcomere by slowing the rate of Ca2+ release from the sarcoplasmic reticulum. PMID- 11201507 TI - Total Ca2+ handling for E-C coupling in the whole heart: an integrative analysis. AB - We assessed total Ca2+ handling (transport, flux) in excitation-contraction (E-C) coupling in a beating left ventricle (LV). We developed a new integrative analysis method that utilizes the internal Ca2+ recirculation fraction (RF), O2 consumption (V(O2)) for Ca2+ handling, and O2 cost of Emax (contractility index) of the LV. We obtained the RF from the beat constant of the exponential decay component of the postextrasystolic potentiation, and the O2 cost of Emax from V(O2) measured at different Emax. Our equation calculated the unknown total Ca2+ handling, futile Ca2+ cycling, and Ca2+ reactivity of Emax from the RF and Ca2+ handling V(O2). The calculated total Ca2+ handling fell between 30 and 110 micromol/kg, depending on Emax and pathological conditions. Our method also allowed an assessment of futile Ca2+ cycling and Ca2+ reactivity of Emax in a beating LV. These data are not available using conventional methods. Our method can be used to better understand the pathophysiology of total Ca2+ handling in a beating heart. PMID- 11201508 TI - Progestogen effects on coronary arteries: the need for definitive clinical trials. PMID- 11201510 TI - Isoflavone-rich or isoflavone-poor soy protein does not reduce menopausal symptoms during 24 weeks of treatment. AB - OBJECTIVE: We examined the change in menopausal symptoms in response to 24 weeks of isoflavone-rich (80.4 mg/day) and isoflavone-poor (4.4 mg/day) soy protein isolate treatment in perimenopausal women. DESIGN: In this double-blind 24-week study, 69 women were randomized to treatment: isoflavone-rich soy protein (n = 24), isoflavone-poor soy protein (n = 24), or whey protein control (n = 21). A Menopausal Index was used to assess change in hot flushes and night sweats, as well as other symptoms, at baseline, week 12, and week 24. RESULTS: Repeated measures analysis of variance indicated no treatment effect on change in hot flush (p = 0.18) and night sweat (p = 0.92) frequency, whereas there was a significant decline in hot flush (p = 0.0003) and night sweat (p = 0.0007) frequency with time in all treatment groups. Chi2 analyses indicated no treatment effect on severity of hot flushes or night sweats at any time point, as well as no treatment effect on frequency or severity of other vasomotor symptoms. At the completion of the study, we found no treatment effect on retrospective perception of frequency, duration, or severity of hot flushes or night sweats. Since time had a significant effect on symptoms with all groups reporting a decline in overall symptoms, this indicated either a placebo effect or simply an improvement in symptoms during the study. CONCLUSION: In this study, we found no evidence that isoflavone-rich or isoflavone-poor soy protein provided relief of vasomotor or of other menopausal symptoms. PMID- 11201511 TI - The effects of sequential combined oral 17beta-estradiol norethisterone acetate on insulin sensitivity and body composition in healthy postmenopausal women: a randomized single blind placebo-controlled study. AB - OBJECTIVE: The androgenic effect of progestogen, necessary in early postmenopausal hormone replacement therapy (HRT), may adversely affect insulin sensitivity as well as body fat distribution and thereby increase the cardiovascular risk profile. The impact of HRT with sequential combined oral 17beta-estradiol and norethisterone acetate on insulin sensitivity and body composition in early menopause has not been studied. DESIGN: A randomized single blind placebo-controlled 6-month study of sequential combined 17beta-estradiol norethisterone acetate on insulin sensitivity and body composition was carried out. Thirty fit healthy postmenopausal women were enrolled and completed this 6 month study. Body composition was measured by dual-energy x-ray absorptiometry scanning, and insulin sensitivity was measured using the euglycemic hyperinsulinemic clamp. Studies were undertaken at baseline and after 6 months of therapy. The studies were performed during the estrogen-only phase of therapy. RESULTS: All women demonstrated a degree of decreased insulin sensitivity that was not modified by 6 months of hormone replacement therapy. Body composition remained unchanged over 6 months. There was no alteration in total body fat or the distribution of body fat. The percentage of central abdominal fat (android) was not altered. CONCLUSION: Six months of HRT with sequential combined oral 17beta-estradiol norethisterone acetate does not have an adverse effect on insulin sensitivity and does not promote an increase in weight or the more android distribution of body fat, which could contribute to the increased cardiovascular risk profile that is evident in postmenopausal women. PMID- 11201509 TI - Sleep in menopause: differential effects of two forms of hormone replacement therapy. AB - OBJECTIVES: The aim of the present study was to evaluate differences between two regimens of estrogen/progestogen replacement therapy on nocturnal sleep in postmenopausal women. METHODS: Twenty-one (21) postmenopausal women were studied. They were randomized into two treatment groups: (1) estrogen (Premarin 0.625 mg) and medroxyprogesterone acetate (Provera 5 mg) (n = 11) or (2) estrogen (Premarin 0.625 mg) and oral micronized progesterone (Prometrium 200 mg) (n = 10). Postmenopausal women were recorded for two consecutive nights in the sleep laboratory at baseline and again after 6 months of treatment in a randomized trial. The women also had to fill out evening and morning sleep and vigilance questionnaires for 7 days before baseline recordings and for 23 days before month 6 recordings. RESULTS: Sleep efficiency was found to be significantly improved in the micronized progesterone group. It increased by 8% (p = 0.014) with no such increase observed in the medroxyprogesterone acetate group. Time spent awake after sleep onset was also significantly improved in the micronized progesterone group but not in the medroxyprogesterone acetate group. On the other hand, menopausal symptoms and subjective measures of sleep (questionnaires) improved in both groups after treatment. CONCLUSION: This study suggests that medroxyprogesterone acetate and micronized progesterone are both effective for treating menopausal symptoms but that the latter might better improve the quality of sleep in postmenopausal women taking estrogen. PMID- 11201512 TI - Menopausal progesterone replacement and sleep quality. PMID- 11201513 TI - Symptom reports from a cohort of African American and white women in the late reproductive years. AB - OBJECTIVE: To identify symptoms experienced in a cohort of healthy women in the late reproductive years; to compare symptom reports between African American and Caucasian women; and to determine the extent to which other factors in reproductive health, mood and behavior, lifestyle, and demographic background are associated with the reported symptoms. DESIGN: A cohort of women aged 35 to 47 years (mean age, 41 years) was identified through random digit dialing. This study is a cross-sectional analysis of data collected at enrollment from a subset of 308 women who completed daily symptom reports (DSR) for one menstrual cycle. Data were obtained in structured interviews and self-administered standard questionnaires. The associations of the study variables with symptoms as assessed by the DSR were examined using analysis of variance and general linear models. RESULTS: The African American women were significantly more likely to report in interview that they experienced menopausal symptoms (46% vs. 30%; p < 0.001) and had significantly higher ratings on the physiological symptom factor of the DSR, which included hot flashes, dizziness, poor coordination/clumsiness, urine leaks, and vaginal dryness. The DSR yielded two other factors of psychological and somatic symptoms. Race was associated only with the physiological symptom factor in the multivariable analyses. Neither race nor age were associated with psychological symptoms, which were predicted by current or past mood problems. CONCLUSIONS: Symptoms commonly associated with the menopause are experienced in the late reproductive years before observable changes in menstrual cycles. African American women reported more physiological symptoms than white women. These data provide an essential baseline for longitudinal study of symptoms associated with the ovarian decline in the perimenopausal years. PMID- 11201514 TI - Influence of endogenous androgens on carotid wall in postmenopausal women. AB - OBJECTIVE: There is increasing evidence of a direct association between normal androgen levels and reduced cardiovascular morbidity and mortality in women. After menopause the influence of estrogens declines, whereas that of androgens increases. Therefore, we investigated the effects of androgens on atherosclerosis in postmenopausal women, by using carotid artery intimal-medial thickness as a marker of vascular damage. DESIGN: Blood pressure, body mass index, waist-to-hip ratio, serum dehydroepiandrosterone sulfate, androstenedione, total and free testosterone, estrone, insulin, lipid profile, and glucose were evaluated in 44 women in stable physiological menopause. All subjects underwent carotid ultrasound (Biosound 2000 II s.a. high-resolution unit). RESULTS: Spearman correlation coefficients indicated that serum androstenedione and free testosterone were negatively associated with several carotid intimal-medial thickness measures with correlation coefficients (r) ranging from 0.477 to 0.397 (p < 0.01-0.04). Moreover, age-adjusted androstenedione and free testosterone highest tertiles showed intimal-medial thickness values significantly (p < 0.03 0.05) lower than the other tertiles. There was a favorable association between hormones and the most important cardiovascular risk factors. This association, however, did not reach statistical significance. Stepwise multiple regression analysis showed that the inverse relationships between the hormones (androstenedione and free testosterone) and several intimal-medial thickness measures were maintained (F: 4.15-6.07, p < 0.05-0.02) after adjustment for major cardiovascular risk factors. CONCLUSIONS: Our data demonstrate that in postmenopausal women endogenous steroid precursors and androgens are inversely related to carotid intimal-medial thickness, an established marker of atherosclerosis. In addition, these hormones show favorable associations with cardiovascular risk factors. Therefore, our study suggests that, after menopause, normal androgen levels may benefit the carotid artery wall. PMID- 11201515 TI - Effect of medroxyprogesterone acetate and norethisterone on serum-stimulated and estradiol-inhibited proliferation of human coronary artery smooth muscle cells. AB - OBJECTIVE: The addition of progestogen to estrogen replacement therapy is thought to antagonize, at least in part, the beneficial effects of estrogens on the vasculature. The aim of this study was to investigate the effect of two progestogens mostly used in clinical practice on the proliferation of vascular smooth muscle cells, which has been demonstrated to be a crucial step in the development of atherosclerosis. MATERIAL AND METHODS: The effect of medroxyprogesterone acetate (MPA) and norethisterone (NET), which represent the two different classes of C21- and C19-progestogens, respectively, was investigated on proliferation of smooth muscle cells from human coronary artery in vitro. The steroids were tested in the concentration range 10(-8) to 10(-5) M, which is in the upper range of that reached during hormonal replacement therapy, and compared with control values. RESULTS: Estradiol significantly inhibited serum-stimulated cell growth at the concentrations 10(-6) and 10(-5) M by 18% and 34%, respectively. MPA significantly enhanced serum-stimulated growth at the concentrations 10(-6) and 10(-5) M by 29% and 47%, respectively. In equimolar combinations of MPA and estradiol, proliferation of the cells was significantly stimulated at the concentrations 10(-6) and 10(-5) M by 26% and 44%, respectively. In contrast, NET had no significant effect on serum-stimulated cell growth and had no impact on the estradiol-inhibited proliferation. CONCLUSIONS: These data suggest that MPA may antagonize beneficial antiatherosclerotic estradiol effects on the vasculature, whereas NET may be neutral in this respect. However, these effects occurred at supraphysiological concentrations. Because these concentrations might be reached in the target tissues, the clinical relevance for treatment of patients with cardiovascular risk cannot be excluded. PMID- 11201516 TI - Higher values of hepatic lipase activity in postmenopause: relationship with atherogenic intermediate density and low density lipoproteins. AB - OBJECTIVE: To investigate the enzymatic activity of hepatic lipase (HL) in postmenopausal women (PMW) and reproductive age women (RAW); and to evaluate the relationship between this enzyme and the atherogenic intermediate density lipoproteins (IDL) and low density lipoproteins (LDL), and antiatherogenic high density lipoproteins (HDL) and its subfractions (HDL2 and HDL3). DESIGN: We studied 55 PMW receiving no hormonal treatment in a cross-sectional study in comparison with a control group of 55 RAW, matched by body mass index. Follicle stimulating hormone was > 40 mUI/ml in PMW and 3-12 mUI/ml in RAW. PMW presented at least 1 year of natural menopause and no more than 10 years of amenorrhea with E2 serum concentration < 15 pg/ml. RESULTS: HL activity was significantly higher in PMW versus RAW (14.0 +/- 1.4 vs. 10.9 +/- 0.4 micromol of fatty acids/ml of postheparin plasma, respectively, mean +/- SEM, p < 0.001). In PMW, IDL cholesterol showed a positive correlation with LDL cholesterol (r = 0.28, p < 0.05), and HDL2 cholesterol was inversely correlated with HL activity (r = 0.31, p < 0.05). HL was positively correlated with plasma concentration of LDL cholesterol in both groups (r = 0.27, p < 0.05). The higher values of HL activity and IDL cholesterol were independent of age. CONCLUSIONS: Higher HL activity is associated with a more atherogenic profile in PMW. PMID- 11201518 TI - Prevalence of osteopenia and osteoporosis in Thai women. AB - OBJECTIVE: To determine the age-specific and age-adjusted prevalence of osteopenia and osteoporosis in pre- and postmenopausal Thai women. METHODS: This was a descriptive study of 1,935 Thai women ranging in age from 40 to 80 years, with randomly selected strata using multistage sampling and stratifying from six representative provinces of the country. After recruiting, all the women were interviewed by a well-trained interviewer using structured questionnaires. Bone mineral density (BMD) of lumbar spine 1-4 and nondominant hip was measured by a dual energy photon absorptiometer. The investigators were trained and standardized; inter- and intraobserver variations were measured periodically. Every BMD outcome was re-examined by the specialist. Age-specific prevalence of osteoporosis and osteopenia were determined using both Thai and Western standard BMD values. Age-adjusted prevalence of osteopenia and osteoporosis was calculated using the age-adjusted direct method. RESULTS: Using the Thai BMD reference, the age-specific prevalence of osteoporosis among Thai women rose progressively with increasing age to more than 50% after the age of 70. The age-adjusted prevalence of osteoporosis also rose progressively. It was 19.8%, 13.6%, and 10% for lumbar spine, femoral neck, and intertrochanteric. The age-adjusted prevalence of osteoporosis indicates the overall magnitude of that condition in the population or country. In our study, using a Western BMD reference resulted in a misleadingly high prevalence of osteoporosis in the population of Asian countries. CONCLUSION: It is important to calculate the age-adjusted prevalence of osteopenia and osteoporosis to address the overall magnitude of the problem in Thai women. This will allow us to predict the socioeconomic impact of preventable chronic conditions such as osteoporosis. The results obtained from this study are important data for public health policy: maximizing bone mass throughout life as well as detection of important risk factors is essential. PMID- 11201517 TI - 17Beta-estradiol inhibits proliferation of cultured vascular smooth muscle cells induced by lysophosphatidylcholine via a nongenomic antioxidant mechanism. AB - OBJECTIVE: Lysophosphatidylcholine (lysoPC), an active component of oxidized low density lipoprotein, stimulates proliferation of vascular smooth muscle cells (VSMC). We investigated the direct impact of 17beta-estradiol (E2) on the proliferation of VSMC from rat aorta. RESULTS: VSMC derived from both female and male rats expressed estrogen receptors alpha and beta. Treatments with 1% fetal bovine serum or 5 microM lysoPC increased the incorporation of [3H]-thymidine in VSMC obtained from female rats. 17Beta-E2 did not alter the response to fetal bovine serum, but significantly suppressed the enhanced deoxyribonucleic acid synthesis which had been induced by lysoPC in a dose-dependent manner (10(-4)-10( 6) M). Estrogen also inhibited the proliferation of VSMC from male animals. ICI 182,780, a specific estrogen receptor antagonist, and 17alpha-E2, an inactive form of estradiol, also decreased the mitogenic response to lysoPC in VSMC. In addition, N-acetyl-L-cysteine, a potent antioxidant, inhibited the lysoPC effect. Flow cytometric analysis using the oxidation-sensitive probe 2',7' dichlorofluorescin diacetate revealed that elevated intracellular formation of reactive oxygen species elicited with lysoPC was depressed significantly by 17beta-E2, ICI 182,780, or 17alpha-E2 as well as by N-acetyl-L-cysteine. CONCLUSION: 17Beta-E2 inhibits in vitro VSMC proliferation induced by lysoPC via a nongenomic antioxidant mechanism. PMID- 11201519 TI - Hormone replacement therapy after invasive ovarian serous cystadenocarcinoma treatment: the effect on survival. AB - AIM: Our report deals with the presumed influence of hormone replacement therapy (HRT) on the survival of patients with invasive ovarian serous cystadenocarcinoma. MATERIALS AND METHODS: We selected a group of 24 patients with the diagnosis of invasive ovarian serous cystadenocarcinoma who were treated with HRT after primary surgical treatment. Each patient from the selected group was compared with two patients from the control group with the same diagnosis who did not receive HRT. The matching criteria were the age at the time of the diagnosis, year of the diagnosis, stage of the disease, differentiation, residual tumor after first operation, and disease-free interval until receiving HRT. We used Cox regression to calculate odds ratios as estimates of the effect of HRT on overall survival in the patients with invasive ovarian serous cystadenocarcinoma who did or did not receive HRT after diagnosis. RESULTS: HRT was started an average of 21 months (range, 1-25 months) after diagnosis, and lasted for an average of 24 months (range, 1-70 months). After taking into account the effects of other known prognostic factors (the age at the time of the diagnosis, stage of the disease, differentiation, type of operation, residual tumour before the first operation), the estimated risk of death in patients with invasive ovarian serous cystadenocarcinoma who received HRT was 0.90 (odds ratio = 0.90; 95% confidence interval, 0.24-5.08). CONCLUSION: The results of our small study are only preliminary and suggest that HRT does not have a pronounced effect on survival. A single center can scarcely obtain a sufficient number of such a specific group of cancer patients; therefore, the collaboration of different institutions, preferably in a randomized, controlled trial, is needed for more reliable results. PMID- 11201520 TI - Clinical effects of a standardized soy extract in postmenopausal women. PMID- 11201521 TI - The effects of HIV infection on endothelial function. AB - Endothelial dysfunction and/or injury is pivotal to the development of cardiovascular and inflammatory pathology. Endothelial dysfunction and/or injury has been described in Human Immunodeficiency Virus (HIV) infection. Elaboration of circulating markers of endothelial activation, such as soluble adhesion molecules and procoagulant proteins, occurs in HIV infection. Certain endothelial cells, such as those lining liver sinusoids, human umbilical vein endothelial cells, bone marrow stromal endothelial cells or brain microvascular endothelial cells, have been shown to be variably permissive for HIV infection. Entry of virus into endothelial cells may occur via CD4 antigen or galactosyl-ceramide receptors. Other mechanisms of entry including chemokine receptors have been proposed. Nevertheless, endothelial activation may also occur in HIV infection either by cytokines secreted in response to mononuclear or adventitial cell activation by virus or else by the effects of the secreted HIV-associated proteins, gp 120 (envelope glycoprotein) and Tat (transactivator of viral replication) on endothelium. Enhanced adhesiveness of endothelial cells, endothelial cell proliferation and apoptosis as well as activation of cytokine secretion have all been demonstrated. Synergy between select inflammatory cytokines and viral proteins in inducing endothelial injury has been shown. In HIV infection, dysfunctional or injured endothelial cells potentiate tissue injury, inflammation and remodeling, and accelerate the development of cardiovascular disease. PMID- 11201522 TI - Effect of high blood flow on the expression of endothelial constitutive nitric oxide synthase in rats with femoral arteriovenous shunts. AB - The effect of high blood flow on the expression of endothelial nitric oxide synthase has been investigated in the femoral arteriovenous shunt (AVS) rats created by inserting U-shaped polyurethane tubes in the left femoral arteries and veins. Three days after inserting the femoral AVS, the mean aortic blood flow rate in the abdominal aorta of the AVS rats was about 2.0 times higher than that in the control rats (110.0 +/- 8.4 ml/min vs 52.7 +/- 2.7 ml/min, p < 0.001). The competitive reverse transcriptase-polymerase chain reaction (RT-PCR) data revealed that the mRNA expression level of the endothelial constitutive nitric oxide synthase (ecNOS) was increased in the aortas of the femoral AVS rats compared to that in the control rats. Western blot analysis using a monoclonal antibody against ecNOS revealed that the ecNOS protein levels were markedly increased in the aortas of femoral AVS rats, but ecNOS protein levels in aortas without endothelium were not significantly increased. Inducible nitric oxide synthase (iNOS) protein was not expressed in the aortic tissues with and without endothelium in the control rats. This iNOS expression was not increased by the high blood flow in the femoral AVS rats. These findings suggest that high blood flow could up-regulate the expression levels of ecNOS mRNA and proteins in femoral arteriovenous shunt rats. PMID- 11201523 TI - Endothelium-dependent vasorelaxation in the aorta of transgenic mice expressing human apolipoprotein(a) or lipoprotein(a). AB - Elevated plasma level of lipoprotein(a) (Lp(a)) is a well established risk factor for premature atherosclerosis and coronary artery disease. Recent studies showed impaired endothelium-dependent vasodilatation in humans with elevated plasma Lp(a). However, these human studies could not determine whether (1) elevated Lp(a) levels alone are the cause of endothelial dysfunction (these patients had multiple risk factors), and (2) native or oxidatively modified Lp(a) contributes to endothelial dysfunction (no measurements of native/oxidized Lp(a) ratio was reported in humans). In order to test whether apo(a) (an essential component of Lp(a) which is required for binding to endothelial cells) and native Lp(a) cause endothelial dysfunction, in the present study we tested endothelium-dependent vasorelaxation in aortic rings isolated from control and transgenic male mice either expressing the human apo(a) gene (TgA) or both the human apo(a) and human apo B100 genes (TgL). The TgA mice had plasma apo(a) levels of 8.8 +/- 1.2 mg/dl (n=6) and the double transgenic TgL mice had plasma Lp(a) levels of 15.3 +/- 1.4 mg/dl (n=8). Isolated aortic rings with and without endothelium were mounted in organ chambers and contracted with U46619 (10(-8) M) in the presence of ibuprofen (10(-5) M). Acetylcholine caused concentration-dependent (10(-9)-10(-5) M) relaxation, which could be prevented by endothelium removal and by NG-L-nitro arginine (10(-4) M). Basal and acetylcholine-stimulated endothelium-dependent relaxation and endothelium-independent relaxation to nitroglycerin (10(-6) M) were not significantly different in aortic rings isolated from control and TgA or TgL mice. Twenty-four hour incubation of aortic rings isolated from control mice with recombinant human apo(a) or native Lp(a) (up to 300 microg/ml) caused no impairment of endothelium-dependent relaxations. In contrast, incubation with oxidized Lp(a) (50 microg/ml) or oxidized LDL (250 microg/ml) caused significant suppression of acetylcholine-induced endothelium-dependent vasorelaxation. These results show for the first time that elevated plasma levels of apo(a) and Lp(a) do not cause endothelial dysfunction in transgenic mice. PMID- 11201525 TI - Hypoxia-reoxygenation inhibits gap junctional communication in cultured human umbilical vein endothelial cells. AB - We studied the change in gap junctional intercellular communication (GJIC) on human umbilical vein endothelial cells (HUVEC) under hypoxia-reoxygenation (H-R) conditions by the fluorescence redistribution after photobleaching (FRAP) method. Confluent HUVEC monolayers were exposed to hypoxia (pO2<0.1%) for 12 hours, and then were returned to normal atmospheric conditions for reoxygenation. Contrast microscopic observation showed no significant changes in the morphology of the HUVEC at any times after H-R. Reoxygenation following hypoxia caused time dependent decrease in GJIC, that is, GJIC reduction was induced after 2 hours and reached maximum at 4-6 hours which recovered to normal levels after 18 hours. Oxidant sensitive fluorescence dye assay revealed that the generation of intracellular free radicals increased during the first 2 hours after reoxygenation. Hydroxyl radical scavengers (MCI-186, DMSO) and an iron chelator (deferoxamine) abolished the reduction of GJIC due to H-R. However, SOD, catalase and probucol were essentially inactive on this reduction. These data suggest that ischemia-reperfusion injury may be caused by a functional defect of GJIC induced by reactive oxygen radicals. PMID- 11201524 TI - Comparison of glycyrrhetinic acid isoforms and carbenoxolone as inhibitors of EDHF-type relaxations mediated via gap junctions. AB - The vascular actions of the lipophilic gap junction inhibitors 18alpha glycyrrhetinic acid (18alpha-GA), 18beta-glycyrrhetinic acid (18beta-GA) and the water-soluble hemisuccinate derivative of 18beta-GA, carbenoxolone, were investigated in preconstricted rings of rabbit superior mesenteric artery. EDHF type relaxations to acetylcholine (ACh), observed in the presence of 300 microM NG-nitro-L-arginine methyl ester (L-NAME) and 10 microM indomethacin, were attenuated by preincubation with 18alpha-GA (to 100 microM), 18A-GA (to 10 microM) or carbenoxolone (to 300 microM) in a concentration-dependent fashion. By contrast, none of these agents affected responses to sodium nitroprusside, an exogeneous source of NO, and relaxations evoked by ACh in the absence of L-NAME were attenuated by only approximately 20%. 18alpha-GA exerted no direct effect on vessel tone, whereas 18beta-GA and carbenoxolone caused relaxations which were maximal at approximately 1 and approximately 10 mM, respectively. Relaxations to carbenoxolone were attenuated by endothelial denudation and by incubation with L NAME, whereas those to 18beta-GA were unaffected. In conclusion, all three agents inhibit EDHF-type relaxations evoked by ACh, providing further evidence for the involvement of gap junctions in such responses. Unlike 18alpha-GA, carbenoxolone and 18beta-GA possess intrinsic vasorelaxant activity which in the case of carbenoxolone involves functional enhancement of NO activity in addition to direct effects on vascular smooth muscle. PMID- 11201526 TI - Regulation of endothelial barrier function by the cAMP-dependent protein kinase. AB - Elevation of cAMP promotes the endothelial cell (EC) barrier and protects the lung from edema development. Thus, we tested the hypothesis that both increases and decreases in PKA modulate EC function and coordinate distribution of regulatory, adherence, and cytoskeletal proteins. Inhibition of PKA activity by RpcAMPS and activation by cholera toxin was verified by assay of kemptide phosphorylation in digitonin permeabilized EC. Inhibition of PKA by RpcAMPS or overexpression of the endogenous inhibitor, PKI, decreased monolayer electrical impedance and exacerbated the decreases produced by agonists (thrombin and PMA). RpcAMPS directly increased F-actin content and organization into stress fibers, increased co-staining of actin with both phosphatase 2B and myosin light chain kinase (MLCK), caused reorganization of focal adhesions, and decreased catenin at cell borders. These findings are similar to those evoked by thrombin. In contrast, cholera toxin prevented the agonist-induced resistance decrease and protein redistribution. Although PKA activation attenuated thrombin-induced myosin light chain (MLC) phosphorylation, PKA inhibition per se did not cause MLC phosphorylation or affect [Ca2+]i. These studies indicate that a decrease in PKA activity alone can produce disruption of barrier function via mechanisms not involving MLCK and support a central role for cAMP/PKA in regulation of cytoskeletal and adhesive protein function in EC which correlates with altered barrier function. PMID- 11201527 TI - Healthy weight. A process of changing your lifestyle habits. PMID- 11201528 TI - Health tips. Caffeine. PMID- 11201529 TI - Can ginkgo biloba treat intermittent claudication? PMID- 11201530 TI - Another reason to stay active--youthful blood vessels. PMID- 11201531 TI - Chronic pain. Considering the role of medication. PMID- 11201533 TI - Multiple medications. How to avoid interactions. PMID- 11201532 TI - Atrophic vaginitis. Estrogen can help. PMID- 11201534 TI - I understand there's a new prescription cream that removes excess facial hair. Could you tell me more about it? PMID- 11201535 TI - I've heard the terms aerobic exercise and anaerobic exercise. What's the difference? PMID- 11201536 TI - Postpartum follow-up of hepatic calcification detected by prenatal ultrasound. AB - The causes of parenchymal hepatic calcification are mostly transplacental infection of TORCH complex, ischaemic necrosis, or tumours of foetal liver including haemangioma, hamartoma, teratoma, hepatoma, and hemangioendothelioma. Vascular pathologies like hepatic artery aneurysm, haematoma, calcified thromboemboli of portal vein and hepatic veins can also cause hepatic calcification. We present a case of hepatic calcification which was first diagnosed by prenatal ultrasound. In the postpartum follow-up, we observed that the calcifications had decreased in number and size. The causes and results of hepatic calcification or underlying disease are discussed with analysis of the literature. PMID- 11201537 TI - Metachronous eosinophilic granuloma of bone. AB - We present the case of a 4-year-old girl who developed a metachronous osseous lesion of the left distal femur five months after successful surgical treatment of an eosinophilic granuloma in the left proximal femur. After treatment of the second lesion with curettage, no further recurrence occurred during a follow-up interval of 17 months. Radiologists should be aware that additional eosinophilic granulomas of bone, occurring in up to four years after the initial diagnosis, should still be interpreted as a localized form of Langerhans'cell histiocytosis with a more favorable prognosis than the multifocal disseminated form, with involvement of organ systems other than the skeletal system. PMID- 11201538 TI - Percutaneous treatment of acute multiple limb ischemia. AB - This study evaluates the use of pulse spray pharmacomechanical thrombolysis (PSPMT) in combination with a low dose urokinase infusion and a possible secondary percutaneous treatment in the management of acute multiple limb ischemia. A retrospective analysis of 185 patients treated with PSPMT revealed eight patients with acute simultaneous ischemia of more than 1 limb. Seven patients presented with acute ischemia of both lower limbs; one patient presented with acute ischemia of the left arm and both lower limbs. All patients were treated using a combination of PSPMT and low dose urokinase infusion. The combination of PSPMT and low dose urokinase infusion was completely successful in 6 cases. In 1 patient with bronchogenic carcinoma PSPMT failed and immediate surgical thrombectomy was performed. In the other patient we obtained clot dissolution with thrombolysis in one leg, residual clots at the popliteal level in the other leg however had to be removed by surgical embolectomy. Embolism was the cause of the occlusion in 6 patients. Atherosclerotic disease appeared to be the underlying cause in the other 2 patients. Atherosclerotic disease was treated with balloon angioplasty and stenting. In the 8 patients with multiple limb ischemia, combination of PSPMT, low dose urokinase infusion, and possibly secondary treatment was useful and constituted a valuable alternative to open surgery. Acute occlusion of the abdominal aorta and acute leg ischemia have a high mortality and amputation rate with variable results in treatment. The use of thrombolysis has reduced the necessity of surgery in arterial occlusive disease and simplifies the treatment of native artery occlusion. Especially in patients with long and multi-level occlusions with poor outflow, thrombolysis seems to be the treatment of choice. In our analysis of 8 cases with acute multiple limb ischemia we review our experience with the combination of pulse spray pharmacomechanical thrombolysis (PSPMT), low dose continuous urokinase infusion and a possible subsequent percutaneous treatment of the obstructing lesion. The final purpose was to investigate if this combination is a successful and safe method in the treatment of acute multiple limb ischemia. PMID- 11201539 TI - [Carotid endarterectomy without arteriography: only dedicated to urgent procedures?]. AB - Duplex examination is presently established as a safe non-invasive and accurate method of evaluating patients with extracranial cerebrovascular disease which usually provides complete information about the extent of carotid artery narrowing Arteriography, in this indication, is an invasive procedure with a total complication rate of 3-4% with 1% of permanent stroke. If it is currently accepted that in emergency conditions (ictus ingravescens, pre-occlusive plaque) or if iodinated contrast media are contraindicated, thrombendarteriectomy can be performed without arteriography it could be extended to most cases. The authors stress the criteria to increase the number of those patients, summarize the pre requisites to achieve this goal, and comment on the future alternative position of MRA. PMID- 11201540 TI - Pediatric cerebrovascular disease. AB - Stroke in children is thought to be a rare phenomenon, but in a pediatric hospital, it is much more common than is expected. The development of rapid MRI imaging with diffusion techniques and MR spectroscopy has brought to the attention of both the neuroradiologists and clinicians that pediatric infarction, in both detection and management, are challenges for the future. Since 1995, cerebral diffusion has been performed at The Children's Hospital of Philadelphia in the evaluation of patients with acute cerebral compromise. Diffusion imaging looks at the motion of water molecules both intra- and extracellular, and the manner in which they become restricted in their motion when higher gradient strength is applied during the imaging sequence. Restricted diffusion is seen in cytotoxic edema, an early acute manifestation of ischemia/infarction. Diffusion studies are often positive when routine MRI and CT are as yet negative. Confirmation of the death of tissue is provided on proton spectroscopy by a rise in lactate from anaerobic glycolysis and a loss of N-acetylaspartate from neuronal death. Confirmation of the diffusion image findings, by mapping the apparent co-efficient (ADC), is also valuable. Application of these techniques, together with magnetic resonance angiography and magnetic resonance venography, is the substance of this paper. PMID- 11201541 TI - Renal infarction as a cause of acute flank pain. AB - Renal infarction results from occlusion of the main renal artery or its distal branches. The clinical picture depends on the extent and the rapidity of the occlusion. Herein, the different imaging modalities (including ultrasonography, computed tomography, magnetic resonance imaging, intravenous urography, and angiography) for diagnozing renal infarction are discussed. The key-modality is computed tomography. Because of the limited warm ischemia time of the kidneys (1.5 hours?) and the time required for diagnosis, there is no real therapeutic relevance in most cases. PMID- 11201542 TI - Helical CT without contrast in the radiological investigation of renal colic. PMID- 11201543 TI - The place of helical CT scanning in acute pulmonary embolism. AB - Pulmonary embolism is a relative common, potentially fatal disorder that clinicians have difficulty detecting and difficulty diagnosing. Deep venous thrombosis (DVT) is the most important source of thrombi. Early and accurate diagnosis is essential for efficient therapy. Therapy is based on long-term anticoagulation and has an important impact on the mortality and morbidity of pulmonary embolism. For the diagnosis of pulmonary embolism, the ventilation/perfusion (V/Q) scan is still the first examination in many instances. A normal V/Q scan or the combination of a low probability scan and a low clinical suspicion are associated with a prevalence of pulmonary embolism of 4%. The combination of a high-probability V/Q scan and a strong clinical suspicion has a prevalence of pulmonary embolism of 96%. All other results should be considered as non-diagnostic. However, the number of non-diagnostic V/Q examinations can be as high as 70%. Nevertheless, an additional pulmonary angiography will be performed in only in 15% of these cases. In the low pre-test probability group (poor clinical suspicion, absence of risk factors and no medical history) the V/Q scan is useful as a screening test ("rule-out" strategy). When the pre-test probability is higher or in other cases in which early diagnosis is necessary ("rule-in" strategy), a contrast-enhanced spiral CT of the pulmonary arteries (possibly in combination with ultrasonography of the lower limbs) is the most accurate examination. PMID- 11201544 TI - Combined CT venography of the lower limbs and spiral CT angiography of pulmonary arteries in acute pulmonary embolism: preliminary results of a prospective study. AB - PURPOSE: To determine the clinical accuracy of combined CT venography (CTV) and spiral CT angiography (SCTA) in patients suspicious of acute pulmonary thrombo embolism. MATERIALS AND METHODS: 278 consecutive patients referred for SCTA for suspicion of acute pulmonary embolism (APE) underwent subsequent evaluation of the veins of the lower limbs and abdomen (CTV) within one examination without additional injection of contrast medium. Sixty-nine patients had no further study. Two hundred and nine patients were included in the study, 199 had US and 51 phlebography (PG) within 48 hours from SCTA-CTV. The investigators were blinded to the results of CT. When results of CTV and US were discordant, phlebography was indicated. RESULTS: SCTA was positive in 89 patients, negative in 119 and indeterminate in 1. CTV was positive in 99 patients, negative in 103 and indeterminate in 7. US was positive in 87 patients, negative in 97 and indeterminate in 15. PG was positive in 21 patients, negative in 29 and indeterminate in 1. Excellent correlation was found between CTV and US (k = 0.84) and moderate correlation between CTV and PG, and US and PG (k = 0.53). CONCLUSIONS: Combined SCTA and CTV is a rapid and accurate one-session examination in patients suspicious of acute pulmonary thrombo-embolism. PMID- 11201545 TI - Cervical vertebral changes caused by vertebral artery tortuosity: assessment using MR angiography. PMID- 11201546 TI - Ultrasound use in cardiothoracic surgery. AB - With the advent of minimally invasive surgical techniques, patients in the United States currently are undergoing safer, more comfortable surgical procedures than in the past. Traditionally, saphenous vein harvesting techniques involved open surgical techniques that could become sources of postoperative complications, including pain, poor wound healing, increased length of hospital stay, and higher costs for the patient and hospital. These complications were the impetus for developing minimally invasive techniques for vein harvesting. Minimally invasive saphenous vein harvesting is performed through small incisions and subcutaneous tunnels. The procedure offers an atraumatic conduit for the coronary artery bypass procedure and decreases the number of leg wound complications. Ultrasound devices currently offer a quick, accurate method for locating veins before harvest, thereby avoiding wound complications and injuries. PMID- 11201547 TI - Focusing on the safe, healthy workplace. PMID- 11201548 TI - The use of neuromodulation for treatment of urinary incontinence. AB - Urinary incontinence (UI) affects many people in the United States. Although the prevalence of UI increases with age, it should not be considered part of the normal aging process. Medication to relax the bladder and behavioral therapy have been used to treat patients suffering from UI, but they often are unsuccessful or poorly tolerated. Neuromodulation through sacral nerve stimulation is a minimally invasive surgical procedure for treatment of urge incontinence. Neuromodulation is becoming the next logical step at many centers for treating urge incontinence after the failure of more conservative measures. PMID- 11201549 TI - Linking philosophy, methodology, and methods in qualitative research. PMID- 11201550 TI - Recommended practices for reducing radiological exposure in the practice setting. PMID- 11201551 TI - Recommended practices for positioning the patient in the perioperative practice setting. PMID- 11201552 TI - Army nurse corps celebrates 100th anniversary. PMID- 11201553 TI - Crime proofing: give your clinic a thorough examination. PMID- 11201554 TI - Advice for condolence letters. PMID- 11201555 TI - Coverage of Western U accreditation questioned. PMID- 11201556 TI - Enjoys Dr. Osborne's articles. PMID- 11201557 TI - Ethical aspects of proof and "alternative" therapies. PMID- 11201558 TI - What is your diagnosis? Soft tissue opacification of the right maxillary sinus and lysis of the maxillary bone. PMID- 11201559 TI - Vicarious liability. PMID- 11201560 TI - Disaster relief management of companion animals affected by the floods of Hurricane Floyd. PMID- 11201561 TI - Comparison of tibial plateau angles in dogs with and without cranial cruciate ligament injuries. AB - OBJECTIVE: To measure and compare tibial plateau angles (TPA) of dogs with cranial cruciate ligament (CrCL) injuries and dogs without CrCL injuries. DESIGN: Prospective study. ANIMALS: 87 dogs. PROCEDURE: Stifle joints were measured from lateral radiographic views to determine TPA in 3 groups: group-1 dogs had CrCL injuries, group-1a dogs, a subgroup of group 1, had 1 unaffected stifle joint, and group-2 dogs had no CrCL injuries. Age, sex, breed, body weight, limb injured, and TPA were recorded for each dog. RESULTS: 56 stifle joints were measured in group-1 dogs; mean TPA was 23.76 degrees , and mean age and weight were 5.7 years and 37.91 kg (83.4 lb), respectively. Fourteen stifle joints were measured in group-1a dogs; mean TPA was 24.71 degrees , and mean age and weight were 5.6 years and 38.06 kg (83.8 lb), respectively. Sixty stifle joints were measured in group-2 dogs; mean TPA was 18.10 degrees , and mean age and weight of these dogs were 4.83 years and 35.85 kg (79 lb), respectively. The most common breeds included Labrador Retriever, Golden Retriever, and Rottweiler. The TPA of dogs in group 1 and group 1a were significantly greater than the TPA of dogs in group 2. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with CrCL injuries have a significantly greater TPA than dogs without CrCL injury. With further investigation, a normal TPA can be determined. In the future, TPA measurements may be used to screen dogs suspected of being susceptible to CrCL injury. PMID- 11201562 TI - Effect of vaccination on experimental infection with Bordetella bronchiseptica in dogs. AB - OBJECTIVE: To determine comparative efficacy of vaccines administered IM and intranasally, used alone or sequentially, to protect puppies from infection with Bordetella bronchiseptica and determine whether systemic or mucosal antibody response correlated with protection. DESIGN: Randomized controlled trial. ANIMALS: 50 specific-pathogen-free Beagle puppies. PROCEDURE: In 2 replicates of 25 dogs each, 14-week-old puppies that were vaccinated against canine distemper virus and parvovirus were vaccinated against B bronchiseptica via intranasal, IM, intranasal-IM, or IM-intranasal administration or were unvaccinated controls. Puppies were challenge exposed via aerosol administration of B bronchiseptica 2 weeks after final vaccination. Clinical variables and systemic and mucosal antibody responses were monitored for 10 days after challenge exposure. Puppies in replicate 1 were necropsied for histologic and immunohistochemical studies. RESULTS: Control puppies that were seronegative before challenge exposure developed paroxysmal coughing, signs of depression, anorexia, and fever. Vaccinated puppies (either vaccine) that were seronegative before challenge exposure had fewer clinical signs. Puppies that received both vaccines had the least severe clinical signs and fewest lesions in the respiratory tract. Vaccinated dogs had significantly higher concentrations of B bronchiseptica reactive antibodies in serum saliva before and after challenge. Antibody concentrations were negatively correlated with bacterial growth in nasal cavity and pharyngeal samples after challenge exposure. CONCLUSIONS AND CLINICAL RELEVANCE: Parenterally and intranasally administered vaccines containing B bronchiseptica may provide substantial protection from clinical signs of respiratory tract disease associated with infection by this bacterium. Administration of both types of vaccines in sequence afforded the greatest degree of protection against disease. PMID- 11201563 TI - Congestive heart failure associated with myxomatous degeneration of the left atrioventricular valve in a parakeet. AB - Congestive heart failure was diagnosed in a 27-year-old Indian ringneck parakeet with exercise-induced dyspnea. A grade IV/VI holosystolic murmur that radiated to the right sternal area was auscultated over the left side of the sternum. Radiography revealed progressive cardiomegaly, hepatomegaly, pulmonary edema, and accumulation of fluid within the coelomic cavity. Echocardiography revealed biatrial enlargement and enlargement of the right ventricle. Doppler recording revealed high velocity left and right atrioventricular valve regurgitation. Treatment with digoxin and furosemide alleviated clinical signs for approximately 10 months. Gross postmortem examination revealed cardiac enlargement and eccentric hypertrophy of both ventricles on cross-section. Pulmonary congestion and edema, hepatomegaly, hepatic congestion, and ascites were also evident. Histologic examination of the heart revealed myxomatous degeneration of the left atrioventricular valve, muscular hypertrophy of the right atrioventricular valve, and biventricular chronic myofiber degeneration and necrosis. PMID- 11201564 TI - Nonenteric Escherichia coli isolates from dogs: 674 cases (1990-1998). AB - OBJECTIVE: To determine nonenteric sites associated with Escherichia coli isolates in dogs and the antimicrobial susceptibilities of the isolates. DESIGN: Retrospective study. SAMPLE POPULATION: 17,000 canine specimens. PROCEDURE: Medical records of 17,000 canine specimens submitted for bacteriologic culture were examined and the number of isolations of E coli was determined. For these cases, records were further examined with respect to body system involvement, sex, concurrent infection with other species of bacteria, and antimicrobial susceptibility. RESULTS: 674 E coli isolates (424 from urine, 62 from the skin, 52 from the respiratory tract, 45 from the ear, 43 from the female reproductive tract, 25 from the male reproductive tract, and 23 from other organ systems) were identified. There was a significantly higher proportion of isolates from urine specimens from spayed females than from sexually intact females or males. Escherichia coli was isolated in pure culture from 65.9% of the specimens. Most E coli isolates were susceptible to norfloxacin (90%), enrofloxacin (87.5%), gentamicin (90.7%), and amikacin (85.9%). CONCLUSIONS AND CLINICAL RELEVANCE: Most nonenteric E coli infections in dogs involve the urinary tract. Amikacin, gentamicin, norfloxacin, and enrofloxacin have the highest efficacy against canine E coli isolates. For E coli isolates from dogs, in vitro susceptibility to commonly used antimicrobial agents has remained fairly stable during the past decade. PMID- 11201565 TI - Results of magnetic resonance imaging in dogs with vestibular disorders: 85 cases (1996-1999). AB - OBJECTIVE: To determine results of magnetic resonance (MR) imaging in dogs with vestibular disorders (VD) and correlate results of MR imaging with clinical findings. DESIGN: Retrospective study. ANIMALS: 85 dogs. PROCEDURE: Information on signalment, clinical signs, and presumptive lesion location was obtained from the medical records, and MR images were reviewed. RESULTS: 27 dogs had peripheral VD, 37 had central VD, and 21 had paradoxical VD. Of the 27 dogs with peripheral VD, 11 (41%) had MR imaging abnormalities involving the ipsilateral tympanic bulla compatible with otitis media (6 also had abnormalities involving the petrous portion of the ipsilateral temporal bone compatible with otitis interna), 7 (26%) had MR imaging abnormalities compatible with middle ear neoplasia, 2(7%) had an ipsilateral cerebellopontine angle lesion, and 7 (26%) did not have MR imaging abnormalities. All dogs with central and paradoxical VD had abnormalities evident on MR images. Of the 37 dogs with central VD, 13 (35%) had an extra-axial lesion, 6 (16%) had an intra-axial lesion, and 18 (49%) had multiple intra-axial lesions. In 23 (62%) dogs with central VD, lesions on MR images corresponded with location suspected on the basis of clinical signs. Of the 21 dogs with paradoxical VD, 12 (57%) had an extra-axial lesion, 5 (24%) had an intra-axial lesion, and 4 (19%) had multiple intra-axial lesions. Location of lesions on MR images agreed with location suspected on the basis of clinical signs in 19 (90%) dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that MR imaging may be helpful in the diagnosis and treatment of VD in dogs. PMID- 11201567 TI - Effect of oral administration of excessive iron in adult ponies. AB - OBJECTIVE: To evaluate the potential of excess dietary iron to cause hepatic lesions similar to those described in horses with suspected iron toxicosis or hemochromatosis. DESIGN: Prospective study. ANIMALS: 6 adult male ponies. PROCEDURE: 4 ponies received 50 mg of iron/kg (22.7 mg/lb) of body weight each day by oral administration of ferrous sulfate, which contained 20% elemental iron; 2 ponies received only the carrier (applesauce). Complete blood counts, serum biochemical analyses, and hepatic tissue biopsies were performed, and serum iron concentrations were measured. Blood and tissue samples were obtained at days 0 and 2, and at the end of weeks 1, 3, 6, and 8 after administration of iron was initiated. Treatment was discontinued after 8 weeks, and hepatic iron concentrations were measured at 28 weeks. RESULTS: Hepatic iron concentrations, serum iron concentrations, percentage saturation of transferrin, and serum ferritin concentrations were increased, compared with baseline and control concentrations, by week 8. Adverse clinical signs or histologic lesions in the liver were not detected in any ponies. At 28 weeks, hepatic iron concentrations had decreased. CONCLUSIONS AND CLINICAL RELEVANCE: Histologic lesions were not seen in the hepatic biopsy specimens obtained from the ponies treated with ferrous sulfate. It was concluded that it would be unlikely for iron toxicosis to develop in adult ponies or horses during a period of < 8 weeks when food or water contained increased amounts of iron. It is suspected that previous reports of hepatopathies in animals with hemosiderin accumulation may represent a primary hepatopathy with secondary hemosiderin accumulation, especially if the only source of iron is via oral consumption. PMID- 11201566 TI - Idiopathic noncirrhotic portal hypertension in dogs: 33 cases (1982-1998). AB - OBJECTIVE: To describe clinical signs, diagnostic findings, and outcome in dogs with idiopathic intrahepatic portal hypertension. DESIGN: Retrospective study. ANIMALS: 33 dogs. PROCEDURE: Medical records of dogs with portal hypertension of intra-abdominal origin were reviewed. Dogs with intra-abdominal portal hypertension of vascular causes or with hepatic histopathologic changes consistent with severe diffuse hepatobiliary disease were excluded. History and results of physical examination, clinicopathologic tests, diagnostic imaging studies, histologic examination, and treatment were summarized. Outcome was determined in 26 dogs. RESULTS: Dogs were referred most often because of ascites, intermittent vomiting or diarrhea, and polydipsia of several months' duration. Microcytosis, high serum alkaline phosphatase and alanine transaminase activities, hepatic dysfunction, urine specific gravity < or = 1.021, and abdominal transudate were the predominant clinicopathologic features. Microhepatia, abdominal effusion, and multiple anomalous venous anastomoses were the major findings of diagnostic imaging. Hepatic histopathologic changes were consistent with idiopathic noncirrhotic portal hypertension and were indistinguishable from those of dogs with surgically created portocaval anastomosis. Outcome was determined for 19 dogs released from hospital; 13 dogs remained healthy with mostly palliative treatment for periods of 5 months to 9 years. CONCLUSIONS AND CLINICAL RELEVANCE: The clinical signs, clinicopathologic test results, portal pressure, and gross appearance of the liver of dogs with idiopathic noncirrhotic portal hypertension may be identical to those of dogs with cirrhosis; therefore liver biopsy is crucial. Because the prognosis for idiopathic noncirrhotic portal hypertension is generally favorable, owners of affected dogs should be discouraged from choosing euthanasia. PMID- 11201568 TI - Fistulation of the auditory tube diverticulum (guttural pouch) with a neodymium:yttrium-aluminum-garnet laser for treatment of chronic empyema in two horses. AB - Two horses with chronic empyema of the auditory tube diverticulum (guttural pouch) were refractory to medical treatment; empyema was bilateral in 1 horse and unilateral in the other. Both horses were treated by fistulation of the cartilage of the pharyngeal orifice by use of a neodymium:yttrium-aluminum-garnet laser in a noncontact manner. To maintain patency of the fistulae, indwelling catheters were placed into the openings created by the laser. For both horses, long-term follow-up did not reveal complications, and both owners were satisfied with results of the procedure. The authors recommend this procedure for horses that are unresponsive to medical treatment for chronic guttural pouch empyema. PMID- 11201569 TI - Subchondral cystic lesions of the proximal extremity of the tibia in horses: 12 cases (1983-2000). AB - OBJECTIVE: To determine clinical and radiographic features of subchondral cystic lesions (SCL) of the proximal extremity of the tibia in horses that could be used to classify these lesions as being related to osteochondrosis or osteoarthritis and to evaluate results of surgical debridement. DESIGN: Retrospective study. ANIMALS: 12 horses with 14 SCL. PROCEDURE: Medical records and radiographs obtained before and after treatment were reviewed. RESULTS: In 6 young horses (8 lesions), SCL were considered to be related to osteochondrosis; all involved the lateral tibial condyle. The remaining 6 horses were mature and had radiographic evidence of osteoarthritis in addition to SCL. Arthroscopic debridement was performed in 4 horses in which lesions were considered to be a result of osteochondrosis and in 3 horses with osteoarthritis. Three horses in which SCL were considered to be a result of osteochondrosis performed athletically after debridement. Two horses with moderate osteoarthritis returned to work after arthroscopic debridement but at a lower level of athletic performance. One horse with SCL related to osteochondrosis responded to medical treatment and went on to race. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that arthroscopic debridement of SCL is feasible in horses in which lesions involve the cranial portion of the lateral or medial tibial condyle, and that treated horses may be able to perform athletically. PMID- 11201570 TI - Risk factors for reduced postoperative fecal output in horses: 37 cases (1997 1998). AB - OBJECTIVE: To determine prevalence and risk factors for development of ileus of the large intestine after surgery in horses, identified by reduced postoperative fecal output (RPFO). DESIGN: Retrospective study. ANIMALS: 37 horses that developed RPFO after undergoing general anesthesia for reasons unrelated to the gastrointestinal tract. PROCEDURE: Fecal output was obtained from medical records as number of defecations per 24-hour period after surgery; RPFO was defined as < or = 3 defecations per 24-hour period after surgery. The reference population included 48 horses that defecated > or = 4 times during the same period. Demographic, clinical, and surgical variables were evaluated for their association with development of RPFO by use of logistic regression analysis. RESULTS: Ten (12%) horses, all of which had RPFO, developed signs of colic after surgery. Horses > or = 5 years old that underwent orthopedic procedures of > 60 minutes' duration and that did not receive phenylbutazone after surgery were at significant risk for developing RPFO. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that after surgery unrelated to the gastrointestinal tract in horses, there is an intermediate clinical phase characterized by reduced fecal output preceding overt signs of colic. Recognition of RPFO may reduce morbidity and mortality of such horses. PMID- 11201571 TI - [Disagreement with an educational intervention program on breast-feeding]. PMID- 11201573 TI - [Comment analysis of the article on hepatitis B and C]. PMID- 11201574 TI - [The Epidemiologic Diagnostic and Reference Institute]. PMID- 11201575 TI - Comparison among three methods for mycobacteria identification. AB - OBJECTIVE: To compare three methods: Biochemical tests, high-performance liquid chromatography (HPLC) and polymerase chain reaction-restriction fragments length polymorphism (PCR-RFLP), for the identification of mycobacteria, and to perform a cost-benefit analysis to define an optimum identification algorithm. MATERIAL AND METHODS: One-hundred-and-seven mycobacteria isolates were identified by the three methods at Instituto de Diagnostico y Referencia Epidemiologicos, between February of 1999 and January of 2000 and the results were compared with those of a reference laboratory using the Q-Cochran statistical test. RESULTS: PCR-RFLP was the most rapid and specific procedure but also the most expensive; biochemical tests excelled for identification of Mycobacterium tuberculosis, but were lengthy and expensive for other mycobacteria; HPLC ranked in the middle for price, speed and specificity. CONCLUSIONS: Considering the expected proportion of M. tuberculosis, the following algorithm was proposed: Initially, biochemical tests should be performed; if the results indicate a non-tuberculous mycobacteria, the isolate should be analyzed with HPLC; if results are unclear, the isolate should be analyzed using PCR-RFLP. Isolates showing a previously undescribed PCR-RFLP pattern should be characterized by DNA sequencing. PMID- 11201576 TI - [Salmonella serotypes identified in Mexican health services]. AB - OBJECTIVE: To identify the different Salmonella strain serotypes isolated at public and private laboratories in Mexico and at the Institute for Epidemiologic Diagnosis and Referral (InDRE). MATERIAL AND METHODS: A total of 24,394 Salmonella strains collected from 1972 to 1999 in public and private health laboratories of Mexico were analyzed with the Kauffmann-White method, using antisera produced by InDRE, according to Centers for Disease Control and Prevention (CDC, Atlanta, GA) standards; 15,843 (64.9%) samples were from human sources and 8,551 (35.1%) from non-human sources. RESULTS: One hundred ninety nine different serotypes were identified. The most frequent serotype in human beings was S. Typhimurium (20.4%), followed by S. Enteritidis (18.3%). In the past few years, the frequency of S. Enteritidis has been increasing, surpassing that of S. Typhimurium since 1991. Presently S. Enteritidis is the most frequently isolated serotype. In non-human sources, S. Derby (13.8%) and S. Anatum (8.5%) are the most frequent strains. CONCLUSIONS: Salmonella serotypes most frequently isolated in Mexico are: S. Typhimurium, S. Enteritidis, S. Derby, S. Agona y S. Anatum. From the epidemiologic standpoint, it is necessary to identify circulating and emerging Salmonella serotypes in order to target pertinent preventative interventions. PMID- 11201577 TI - [Natural Trypanosoma cruzi infection of Triatominae bugs associated with human habitations in Mexico ]. AB - OBJECTIVE: To estimate the prevalence of infection with Trypanosoma cruzi in Triatominae species frequently found in and around Mexican dwellings, and to assess the frequency of Triatominae in towns by state. MATERIAL AND METHODS: Between January 1993 and December 1999, 5,399 Triatominae bugs from 14 states of Mexico, were received in the Department of Entomology of the Institute for Epidemiologic Diagnosis and Referral (InDRE), for taxonomic determination and parasitoscopical search of Trypanosoma cruzi. Results obtained between 1993 and 1999 were analyzed globally. RESULTS: From 13 bug species associated with human dwellings, nine were naturally infected with T. cruzi. The highest percentage of infection occurred in Triatoma pallidipennis, T. picturata, Rhodnius prolixus and T. longipennis. Nayarit, Morelos, and Michoacan were the states with the highest percentage of infected bugs. The species T. dimidiata, T. gerstaeckeri, T. longipennis, T. mexicana and T. pallidipennis were first state records and Pastrongylus rufotuberculatus was a first local record. CONCLUSIONS: These findings stress the importance of studying the biology of Triatominae and the need for permanent surveillance, to allow for up-to-date distribution records of Triatominae species in and around human dwellings, those adapting to human dwellings, and frequencies of those naturally infected by T. cruzi. PMID- 11201578 TI - [Stature of Chilean parents and children of different ethnicity and social vulnerability]. AB - OBJECTIVE: To analyze and compare the heights of first-year school children and their parents, according to ethnic background and socioeconomic status. MATERIAL AND METHODS: This is a cross-sectional study of indigenous and non-indigenous school children and their parents, belonging to three levels of social vulnerability: very high (poverty), medium, and very low. An indigenous school child was defined as any child having all four parental surnames of Mapuche origin; non-indigenous were those having Hispanic parental surname. Height was compared using Z scores, using WHO nutritional change reference values. Statistical analysis consisted in comparing differences of mean heights between parents and their children. Differences were assessed using Scheffe's method. RESULTS: Improvement in socioeconomic conditions was associated with increasing mean parental height (p < 0.001), except for indigenous mothers, who showed no height increase. Fathers from highly impoverished counties were 4 cm shorter than those living in very low vulnerability areas; height differences reached 2 cm among mothers (p < 0.001). Indigenous school children showed a positive height gradient with improving socioeconomic conditions (p < 0.001). This was not observed among non-indigenous children. When comparing parental height with children's height, children had a better height/age ratio than their parents (p < 0.01). This was specially evident among indigenous school children, who had on average 1.4 Z scores more than their parents. CONCLUSIONS: The upward height gradient related to improved social conditions, and the better height/age ratio seen in children in comparison to their parents, regardless their ethnic background and level of social vulnerability, is encouraging and suggests that interventions directed to the poorest groups, including the indigenous population, must be carried out. PMID- 11201580 TI - [Perceptions and practices related with tuberculosis and treatment compliance in Chiapas, Mexico]. AB - OBJECTIVE: To identify health perceptions and practices and non-adherence to therapy among tuberculosis patients. MATERIAL AND METHODS: Qualitative research work consisting of 11 group interviews with 62 tuberculosis patients during 1997 1998 in the Central, Highlands, and Border Regions of Chiapas, Mexico. RESULTS: Perceived causes of tuberculosis included contagion via food utensils, excess work, malnutrition, and cold, as well as other causes unrelated to person-to person contagion. The resulting incapability to work resulted in an economic crisis for both the patients and their family members. As a result of the social stigma imposed by the disease, patients perceived a negative impact on their personal life, family, work, and community. CONCLUSIONS: Lack of knowledge regarding tuberculosis is an important factor in the selection of and adherence to different care alternatives. Inadequate care provided by health services, including an unsatisfactory physician-patient relationship, resulted in diagnostic delay and non-adherence to therapy. Education programs to promote basic knowledge regarding tuberculosis and its treatment are necessary in this region. PMID- 11201579 TI - [Malignant mesothelioma: clinical and radiological description of 45 cases with and without asbestos exposure]. AB - OBJECTIVE: Our aim was to identify and describe the main symptoms, clinical presentation, and radiographic changes in malignant mesothelioma (MM) patients. MATERIAL AND METHODS: We reviewed the medical and X-ray records of all patients diagnosed with MM, admitted between 1991 and 1998 to the National Institute of Respiratory Diseases (INER), which is a governmental institution specialized in chest disease in Mexico City. The following data were collected: Age, occupation, asbestos exposure, latency, family history of cancer, clinical symptoms, and X ray changes. Data are presented as percentages by sex and age group. RESULTS: We found 45 cases of MM; in 80% of them a history of asbestos exposure could not be documented. The 51-60 years age group had the highest frequency of MM. Dispnea and chest pain were the presenting symptoms in most patients. Pleural effusion and pleural thickening were the X-ray abnormalities observed in 75% of the patients. CONCLUSIONS: The clinical and radiographic findings among patients with MM without asbestos exposure were similar to those with a history of asbestos exposure. PMID- 11201581 TI - [Diagnosis and prevalence of arterial hypertension in persons under 19 years of age in the city of Colima]. AB - OBJECTIVE: To assess the prevalence of high blood pressure among young children. MATERIAL AND METHODS: This is a cross-sectional study, conducted in 1992 in Colima City, Mexico. Blood pressure readings were obtained from 400 children aged under 19. Statistical analysis consisted of calculation of means, variance, and Anova by group age. Association between age and blood pressure was assessed with correlation and determination coefficients. Comparisons by sex were made using Student's t, F, Mann-Whitney's U, and Z tests. Percentile 95th was used to define normal figures. RESULTS: A lineal correlation coefficient was found and confirmed by the determination coefficient. Groups where this association was statistically significant at p < 0.01 were: a) children aged under 2; b) children from 2 to 13 years of age; and c) those over 13 years of age. High blood pressure figures for each group were: a) 92/50 mm/Hg; 110/70 mm/Hg; and 133/84 mm/Hg, respectively. CONCLUSIONS: The prevalence of high blood pressure in younger children may be 8% for systolic pressure and 9% for diastolic pressure. PMID- 11201582 TI - [Ecological studies]. PMID- 11201584 TI - [Certification and recertification of medical specialists in public health]. PMID- 11201583 TI - [Basic information about resources and services of the National Health System, 1994-2000]. PMID- 11201585 TI - [Activities of the Epidemiologic Diagnostic and Reference Institute of Mexico]. PMID- 11201586 TI - Vascular risk factor profiles in the first phase of the Scottish Heart and Arterial Risk Prevention (SHARP) Survey, 1991-1996. AB - BACKGROUND: The SHARP survey data comprises personal information, family history, lifestyle and risk factor prevalence for 19,400 men and women sampled from the Scottish working population between 1991 and 1996. The purpose of the survey was the achievement of a clearer understanding of coronary risk factor prevalence in the working population of Scotland; the education of that population through counselling and advice; and a clearer appreciation of an individual's risk factor profile as a predictor for future events. In this paper a selection of attributes is explored for the information they yield about the characteristics of an apparently healthy population. Comparisons are drawn with earlier studies. METHODS: A mobile risk factor screening unit toured workplaces throughout Scotland and recorded information on age, sex, occupation, social class, personal and family history, smoking, alcohol and salt consumption, body mass index, blood pressure, glucose and total cholesterol. RESULTS: The variation in measured levels for common risk factors in a sample of apparently healthy Scottish people shows substantial differences from the measured variation in an unstratified survey. CONCLUSIONS: Across all conventional coronary risk factor measurements, working Scottish people are uniformly "more healthy" than the general population. A comparison of trend with age for male and female smokers and non-smokers in cholesterol level shows no difference between smokers and non-smokers; a similar comparison for body mass index and weight shows some consistent differences but without statistical significance. PMID- 11201587 TI - Risk factors in young patients with peripheral atherosclerosis. AB - BACKGROUND: Risk factors and especially the combination of multiple risk factors are associated with the development of atherosclerosis. Therefore, patients with an early manifestation of atherosclerotic disease are likely to show an extraordinary risk profile. We analysed the frequencies and severity of risk factors in young patients with manifest peripheral arterial occlusive disease as compared to old patients. METHODS: We analysed the risk profiles in 303 patients who were sent for interventional treatment of a symptomatic peripheral arterial occlusive disease. The risk profiles were described for different age groups (54 patients under 50 years of age, 194 patients from 51 to 74 years, 55 patients over 75 years). Multiple linear regression analysis and analysis of variance were performed to look for age-dependent effects. RESULTS: Elevated total cholesterol, and triglyceride levels and nicotine abuse were more frequent in patients younger than 50 years. Diabetes mellitus and hypertension were more frequent in patients older than 75 years. The different frequencies for smoking, diabetes mellitus and hypertension were age-related (p<0.05). Concerning laboratory parameters such as HDL- and LDL-cholesterol, fibrinogen, lipoprotein(a) and homocysteine there were no relevant age-related differences in frequency nor in absolute values with the exception of the hematocrit and uric acid. The coincidence with clinically manifest myocardial infarction was 11.15% in the patients under 50 years compared to 20.6% in those aged 51-74 years and 16.4% in those over 75 years, for cerebral stroke it was 5.6%, 17.5% and 14.5%, respectively. Patients under 50 years with peripheral arterial occlusive disease and a history of myocardial infarction were characterised by high levels of total cholesterol, triglyceride and lipoprotein(a). Excluding patients with prior myocardial infarction patients did not show any difference in risk profile between the three age groups. CONCLUSIONS: In a population suffering from manifest peripheral arterial occlusive disease the risk profile in patients under 50 years is not different from that in older patients. In contrast an additional myocardial infarction in such a population is associated with pathological lipid profiles. PMID- 11201588 TI - Comparison between exercise whole body thallium imaging and ankle-brachial index in the detection of peripheral arterial disease. AB - BACKGROUND: Exercise whole body thallium imaging and rest/exercise ankle-brachial index can provide evidence of peripheral artery disease at the stage of intermittent claudication. The aim of this study was to compare both methods in the detection of asymptomatic peripheral artery disease. METHODS: EXPERIMENTAL DESIGN: prospective non-randomised study. SETTING AND PATIENTS: general community, private practice, ambulatory patients referred in a Nuclear Medicine Department for exercise myocardial scintigraphy. Intermittent claudication was present in 8% of the whole study population. Coronary artery disease and diabetes were respectively present in 70% and 16% of the same population. MEASURES: rest/exercise ankle-brachial index and exercise whole body thallium imaging were measured in 105 patients (76 men and 29 women, mean age +/- 1 SD= 61 +/- 10 year) who performed a near-maximal or maximal treadmill test. Normal values of regional blood supply and indices of asymmetry at different levels of legs were determined in 14 patients with a very low probability of peripheral artery disease. RESULTS: The probability of peripheral artery disease was very high in 19 patients (group 1), because of abnormal rest and/or exercise ankle-brachial index, whereas in the 86 remaining patients, the index at rest and exercise was quite normal (group 2).With respect to rest and/or exercise ankle-brachial index, the sensitivity, specificity, positive and predictive negative value of exercise scintigraphy abnormalities were respectively 89%, 62%, 34% and 96%. The false positive scan group differed from the true positive group only by sex and redistribution of thallium 201. The proportion of diabetic patients was the same (15%) in both groups. CONCLUSIONS: Exercise whole body thallium imaging might contribute without additional cost to the detection, functional evaluation and/or risk stratification of peripheral artery disease in patients who perform exercise myocardial scintigraphy. PMID- 11201589 TI - Determining the stage of organisation and natural history of venous thrombosis using computer analysis. AB - BACKGROUND: In vitro studies have shown that as the organisation of a thrombus progresses its ultrasound appearance becomes more echogenic. When diagnosing a deep vein thrombosis (DVT) using duplex ultrasound, an estimation of the degree of organisation of the thrombus is made by assessing its echogenicity. This method is purely subjective and has many pitfalls. METHODS: A study was performed on 100 proximal DVTs from 89 patients diagnosed by duplex ultrasound. These images were transferred to a computer and standardised using, the adobe Photoshop. The thrombus in the image frame was outlined and the grey scale median (GSM) calculated. The grey scale median which is a measure of the echogenicity of the thrombus (indicating the degree of organisation), varied considerably from patient to patient. RESULTS: The results show that the level of organisation of a thrombus on initial diagnosis is unrelated to the clinical signs or duration of symptoms of the patient. This has further implications when considering a therapy regimen based on the duration of symptoms (e.g. thrombolysis). Additionally, the age of the patient, predisposing factors and bulk of the thrombus appear to be unrelated to the value of the grey scale median at the initial visit. The initial grey scale median values were then compared to those at a one week's follow-up examination. Those with a low initial value of the grey scale median were found to increase, indicating further organisation, as expected. However, patients with higher initial grey scale median values were found to fluctuate, some increasing and some decreasing. The increase the grey scale median was due to a more homogenous appearance across the thrombus as the organisation process became more established. A decrease in grey scale median indicated areas of lysis occurring within the thrombus. CONCLUSIONS: Measuring the value of the grey scale median is a quantitative way of assessing the degree of organisation of a deep vein thrombosis. This can be used to asses the suitability of patients for various treatment regimen. It is also a useful means of assessing the long-term implications of different therapies and could aid in determining the long-term outcome for the patient. PMID- 11201590 TI - Color Doppler sonography of arteries associated with perforating veins. AB - BACKGROUND: It has been known for some time that perforating veins had associated perforating arteries. There has been no way to investigate these arteries preoperatively. The newer high resolution ultrasonic devices enable us to investigate these arteries. We are able to localize, determine the frequency, and measure the size of the arteries associated with perforating veins of the lower extremities. METHODS: All patients were studied in our clinical vascular laboratory. PATIENTS: 55 patients with different degrees of varicosities were studied. MEASURES: Each patient had their perforating veins and arteries investigated with a 7.5 MHz linear array transducer (Siemens, Type Elegra). RESULTS: 73% of the 233 perforating veins identified had an associated perforating artery. No preferred localization of the perforating veins was noted. The number of location did not correlate with the presence or absence of incompetence of the veins. The perforating arteries were located in close proximity to the perforating veins but did not go far into the subcutaneous fat. The maximum systolic velocity was 12+/-8 cm/sec. CONCLUSIONS: The preoperative detection of perforating arteries associated with perforating veins is possible using a color Doppler scanner. Their pathophysiological function and its relation to bleeding complications, wound healing and ulcer healing can be studied using this tool. PMID- 11201591 TI - The value of dipyridamole thallium scintigraphy and dobutamine stress echocardiography as predictors of cardiac complications following reconstruction of the abdominal aorta. AB - BACKGROUND: The aim of this study was to evaluate the ability of dipyridamole thallium scintigraphy and dobutamine stress echocardiography to predict cardiac complications following elective reconstruction of the abdominal aorta in patients with a stable preoperative cardiac condition and to compare this with information obtained from the medical history, ECG and resting echocardiography alone. METHODS: This evaluation was performed from January 1993 until December 1995 as part of a prospective, randomised study in 200 patients, with a mean age of 65 (5% women). Dipyridamole thallium scintigraphy was performed on 195 patients and dobutamine stress echocardiography was added to the protocol in the last 83 patients. Cardiac complications were defined before the start of the study. RESULTS: In the postoperative period 62 cardiac complications occurred (31%). In patients clinically suspected of having coronary artery disease the incidence of complications was 40% (51/126), compared to 15% (11/74) when no coronary pathology was suspected (p<0.001). When reversible defects were present on dipyridamole thallium scintigraphy the incidence of complications was 36% (20/55), compared to 29% (41/140) when no reversible defects had been found (NS). Dobutamine stress echocardiography was impossible or contraindicated in 21 patients. In the remaining patients the incidence of complications was 71% (5/7) when new regional wall motion abnormalities were found, compared to 16% (9/55) when such abnormalities had not been detected (p<0.005). CONCLUSIONS: These data suggest that cardiac complications following reconstruction of the abdominal aorta in patients with a stable cardiac condition are best predicted by dobutamine stress echocardiography. Dipyridamole thallium scintigraphy, however, does not seem to be useful in this respect. PMID- 11201592 TI - Cranial nerve dysfunction following carotid endarterectomy. AB - BACKGROUND: Carotid endarterectomy (CEA) is the most common surgical procedure performed for the treatment of symptomatic carotid stenosis greater than 70%. Among the recognised complications, such as stroke and myocardial infarction, is injury to cranial nerves. METHODS: We report the incidence and follow-up of cranial nerve injury in 269 patients who underwent carotid endarterectomy between January 1994 and December 1997 at the Royal Liverpool University Hospital. RESULTS: Fifteen cranial nerve injuries were documented (5.6%). Seven patients (2.6%) had unilateral vocal cord paralysis, nine (3.3%) hypoglossal palsy, two (0.7%) glossopharyngeal nerve injury and one (0.4%) facial nerve palsy (marginal mandibular nerve). All patients showed improvement within a few weeks and none had residual disability at the last follow-up (two weeks to 14 months). CONCLUSIONS: Patients manifesting symptoms of cranial nerve dysfunction should undergo a thorough otolaryngological evaluation and long-term follow-up. Most cranial nerve injuries are transient and result from trauma during dissection, retraction or carotid clamping. Knowledge of cranial nerve anatomy is essential if the surgeon is to avoid such injuries. PMID- 11201593 TI - Carotid artery reconstruction for Takayasu's arteritis the necessity of all autogenous-vein graft policy and development of a new operation. AB - BACKGROUND: We have adopted an all-autogenous-vein-graft policy in carotid reconstruction for Takayasu arteritis, namely an ascendo-right carotid and right subclavian (axillary) arteries bypass using a pantaloon vein graft for patients all of whose arch branches are occluded, and an extra-anatomical bypass from the right subclavian artery for patients whose brachiocephalic artery is the only arch branch that remains patent. This report is to elaborate on these operations and to assess the long-term outcome. METHODS: Six patients were operated on according to this policy; (5 women, 1 man, age range: 14 to 59 years (mean: 30). The indications for surgery were severe cerebral ischaemia that significantly interfered with their daily lives. The pantaloon vein graft bypass was performed in four patients, and an extra-anatomical bypass in two. The specific management protocol to prevent the "postbypass hyperperfusion syndrome" and cerebral oedema included a shunt procedure to the internal carotid artery using one limb of the pantaloon vein graft, induced hypotension just before the completion of the carotid reconstruction and the administration of a glycerine-fructose solution. RESULTS: Cerebral ischaemic symptoms disappeared in all patients. All but one, who died of a ruptured thoraco-abdominal aneurysm on the 35th postoperative month, are living a normal life with a patent graft. No suture line complications have as yet been encountered (follow-up: 10 to 205 months, mean: 126 months). CONCLUSIONS: Carotid vein bypass for Takayasu arteritis, particularly, the pantaloon vein graft bypass is recommended for those of whom all aortic arch branches are occluded, resulting in severe brain ischaemia. Perioperative blood pressure control is important for prevention of the hyperperfusion syndrome. PMID- 11201594 TI - Colour duplex sonography-guided local lysis of occlusions in the femoro-popliteal region. AB - BACKGROUND: To evaluate colour duplex sonographic guidance of local lysis of occlusions in the femoropopliteal region. METHODS: Thirteen consecutive patients (8 female, mean age 67) with peripheral artery disease with acute and subacute occlusions in the superficial femoral or popliteal artery were included in this study. The lesions were identified by colour duplex ultrasound (Acuson 128 XP/10) After anterograde puncture the guidewire was advanced through the arterial lesions under B-mode image control. The Mewissen Infusion Catheter and a Katzen infusion wire were then accurately positioned within the lesion under B-mode image control. The fibrinolytic drugs were then inserted into the occlusions, initially 2.5 mg rt-PA as a bolus followed by Urokinase (50,000 IU/h) for 24 hours. After control duplex sonography (over 24 hours) the additional angioplasty was performed either under fluoroscopic or exclusively under ultrasound guidance. RESULTS: Eleven of 13 patients with occlusions in the femoro-popliteal region were partially recanalised after ultrasound guided local lysis and after the additional angioplasties (nine under fluoroscopic and three under ultrasound guidance) the arteries were completely recanalised. CONCLUSIONS: Our data show that not only is the positioning of the catheter and the guidewire for local lysis exclusively under colour duplex guidance possible, but also the surveillance of the local lysis and the additional angioplasty. In the case of any complications, however, easy access to angiography should be possible. PMID- 11201595 TI - Patency after revision surgery for failing infrainguinal vein grafts. AB - BACKGROUND: Although the results of bypass surgery on arteries in the lower extremities have been greatly improved during the last decades, there are still a significant number of primary failures. In order to investigate the reasons for the failure of autogenous vein grafts after infrainguinal arterial bypass surgery and to ascertain the results of revision operations on the failing grafts, we conducted a clinical study. METHODS: Retrospective study on 104 patients who underwent infrainguinal arterial revascularisation with autogenous veins. RESULTS: One hundred and twenty-six bypasses were constructed in 121 limbs. Seventy-nine of these were for claudication and 47 for threatened limbs (rest pain or ischaemic tissue loss). Five-year primary and secondary patency rates were 69.7% and 84.9% respectively. Spliced or suture-repaired grafts had a poor outcome; five out of seven eventually becoming thrombosed. On the other hand, revision operations for failing but not yet thrombosed grafts produced good results; the five-year primary patency rate after these operations was 76.0%, whereas after single-segment primary grafting it was 72.1%. CONCLUSIONS: These results stress the importance of vigilant follow-up and active intervention for failing grafts. Poor outcome with injured vein grafts emphasizes the importance of meticulous vein harvesting. PMID- 11201596 TI - Can endothelial seeding enhance patency and inhibit neointimal hyperplasia? Experimental studies and clinical trial of endothelial seeded venous prostheses. AB - BACKGROUND: Venous prostheses have poor long-term patency; to improve this situation, experimental studies have been carried out. METHODS: Methods of endothelial cell harvesting, prosthetic seeding and implantation mainly in the inferior vena cava were studied in 127 dogs. Evaluations were conducted by angiography, gross appearance, light, scanning and transmission electron microscopic observations, histo-fluorescent staining, as well as radioimmunoassay. RESULTS: It was found that at five to ten days following implantation, the prosthetic endothelialisation could be reliably achieved in the seeded group and a 100% patency of the seeded inferior vena caval prostheses was attained at 100 days. The thickness of the neointima in the seeded group at 10 and 100 days was 299 microm and 302 microm, respectively. The metabolite of PGI2 from extrinsic arachidonic acid, 6-keto PGF1a, produced by cells from seeded graft was significantly higher than that from spontaneously formed cells and the reverse found with thromboxane B2. A temporary (one week) distal (femoral) arteriovenous fistula enhanced graft patency. These results indicated that the early endothelialisation of grafts by seeding enhanced the patency and inhibited intimal hyperplasia of venous prostheses. The clinical outcome was impressively improved from our previous experience with ten of eleven venous grafts patent over a follow-up period of six to nine years. These might result from the realization of early endothelialisation and its cells derived from seeding being able to produce significantly more PGI2 and less thromboxane B2. CONCLUSIONS: The endothelial cell seeding technique may bring us much closer to an ideal venous prosthesis. PMID- 11201597 TI - Aortic aneurysm in patients with autoimmune diseases treated with corticosteroids. AB - BACKGROUND: Aortic aneurysm is a rare but life-threatening cardiovascular complication in patients with autoimmune disorders. The purpose of this study was to clarify the characteristic clinical features and the pathological mechanism of aneurysmal formation in those patients treated with corticosteroids. METHODS: Among 429 patients operated on for abdominal aortic aneurysm during the past 10 years, six patients with autoimmune diseases treated with corticosteroids (one with progressive systemic sclerosis, one with rheumatoid arthritis and four with systemic lupus erythematosus) were reviewed retrospectively. Their data were compared with those of 391 patients with atherosclerotic aneurysms with no autoimmune disorders. The resected aneurysmal walls of the six patients were also compared histopathologically with those of the last six consecutive patients in the control group. RESULTS: The average age of the patients with autoimmune disease was younger than that of the control group (53.8+/-16.6 vs 71.8+/-7.8 years; p<0.05). Patients with autoimmune disease had received long-term corticosteroid therapy for 15-32 years; mean 22.2+/-6.5 years. Pathological examination showed that the destructive change of the medial elastic lamina in the autoimmune disease group was wider than that in the controls. Most patients had no complications in the postoperative follow-up period (5.1+/-3.2 years), while one patient died of rupture of a dissecting aneurysm two years after operation. CONCLUSIONS: Prolonged corticosteroid treatment probably plays a major role in the disintegration of connective tissue of the media, possibly together with primary aortic wall involvement and/or vasculitic damage in patients with autoimmune disorders, which can result in aortic aneurysmal enlargement. PMID- 11201598 TI - Relationship between aortic calcification and atherosclerotic disease in patients with abdominal aortic aneurysm. AB - BACKGROUND: Calcification of the aortic wall has been used as an index of the degree of complicated atherosclerotic plaque formation. Atherosclerosis in the abdominal aorta in patients with abdominal aortic aneurysm (AAA) was studied by measuring aortic calcification via computerised tomography. METHODS: DESIGN: retrospective study. PATIENTS: preoperative computer tomography (CT) in 129 male patients with a mean age of 68.6 years (range: 42 to 82) undergoing elective aneurysmectomy. MEASUREMENTS: a conventional CT scanner was used. Aortic calcification was assessed at four levels: (A) the origin of the coeliac artery, (B) the left renal vein, (C) the maximum diameter of the aneurysm, and (D) the aortic bifurcation. Calcification was graded as: (0) no calcification, (1) calcification less than 40% of the aortic circumference, or (2) calcification more than 40% of the aortic circumference. The relationships between aortic calcification at each level and various factors related to atherosclerosis were analysed. RESULTS: Maximum calcification was seen at level D, followed by levels C, B and A, in that order. Calcification was less common in patients younger than 50 years old. Hypertension, coronary artery disease, and peripheral vascular occlusive disease correlated with the incidence of aortic calcification. CONCLUSIONS: A correlation between aortic calcification and atherosclerotic disease was demonstrated in patients with abdominal aortic aneurysm. PMID- 11201599 TI - Submucosa of canine small intestine as an alternative medium-diameter autogenous arterial graft. AB - BACKGROUND: Small intestinal canine submucosa has been used in previous studies as a large diameter arterial graft and has shown acceptable patency rates. The aim of our experimental study was to assess its effectiveness when it is used as an autogenous medium-sized diameter arterial graft (5-7 mm). METHODS: Fifteen mongrel dogs were included and underwent laparotomy under general anaesthesia. The mucosa, tunica muscularis and serosa were removed from a resected intestinal segment. The remaining tube, which consisted of the submucosa and the basilar tunica mucosa, represented the experimental graft which was used to replace a proportional gap of the canine infrarenal aorta. Ascertainment of peripheral pulses, measurement of the intra-aortic pressures, aortography and in vivo/in situ observation before the sacrifice of the animals, were the procedures used for verification of the graft's patency. RESULTS: The resistance to thrombogenicity of the graft was considered satisfactory: nine out of 10 grafts remained patent for postoperative intervals ranging from one day to one year; one graft showed partial obstruction due to a technical perioperative error. The grafts showed also excellent physical characteristics (ease of handling and suturing, blood impermeability and durability), resistance to infection and showed no tendency to develop myointimal hyperplasia. CONCLUSIONS: Small intestinal canine submucosa showed satisfactory haemodynamic properties, long term patency and resistance to infection, when used as a medium-diameter arterial substitute. PMID- 11201600 TI - Extra-cranial branch of the internal carotid artery. AB - It has been argued in recent years that angiography is no longer essential before undertaking a carotid endarterectomy, relying solely on a carotid duplex scan. A case is presented where an extra-cranial branch of the internal carotid artery was found at surgery. This unexpected finding was obviated having obtained preoperative angiograms. Anomalies of the internal carotid artery are reviewed. PMID- 11201601 TI - Successful management of aortoiliac aneurysms with a quadrifurcated prosthesis. AB - Aortoiliac aneurysms constitute one of the main challenges facing vascular surgeons worldwide. We report for the first time the successful reconstruction of the aorta and iliac arteries with a quadrifurcated prosthesis, in a 72-year-old man with an infrarenal abdominal aortic aneurysm, and aneurysms of the iliac arteries involving both iliac bifurcations. The aortoiliac reconstruction was performed with a quadrifurcated knitted Dacron graft, revascularising both internal and external iliac arteries. In our opinion, the use of such a graft is recommended in aortoiliac revascularisations whenever it is advisable for the preservation of flow to internal iliac arteries. PMID- 11201602 TI - Primary aorto-oesophageal fistula due to oesophageal carcinoma. Report of a successfully managed case. AB - Aorto-oesophageal fistula is a rare but often fatal entity causing upper gastrointestinal bleeding. Amongst the different aetiologies described, the commonest is rupture of a thoracic aortic aneurysm into the oesophagus. This entity was first reported in 1818, and only recently have successfully treated cases been published. Other causes such as postoperative complications, tuberculosis and trauma are less common. Oesophageal malignancy perforating the aorta is a rarity. The authors describe a case of aortic perforation secondary to an oesophageal carcinoma, treated with initial success. The clinical onset was a massive upper gastrointestinal haemorrhage. The diagnosis, once the bleeding was controlled, was arrived at after CT-scanning and arteriography. A Dacron prosthesis was interposed into the descending thoracic aorta to restore aortic flow; later an oesophagectomy plus oesophagostomy and jejunostomy were carried out. PMID- 11201603 TI - Sutureless vascular reconstruction with titanium clips. PMID- 11201604 TI - Aggregate formation and degradation of overexpressed wild-type and mutant urate oxidase proteins. Quality control of organelle-destined proteins by the endoplasmic reticulum. AB - To analyze the cellular response caused by the overexpression of proteins in subcellular compartments, we constructed four expression clones encoding wild type peroxisomal urate oxidase (UO), truncated UO lacking the peroxisomal targeting signal (UOdC), and chimeric UOs with a mitochondrial targeting signal (MTS) at the N-terminus of UOdC (MUOdC) or UO (MUO). After transfection, we examined COS-1 and HEK293 cells by immunofluorescence and immunoelectron microscopy, transmission electron microscopy, and pulse-chase experiments. The overexpressed UO and UOdC formed large electron-dense aggregates with no limiting membrane in both the cytoplasm and the nucleus. The UO aggregates exhibited the crystalloid structure quite similar to that of rat liver peroxisomal cores, whereas the UOdC aggregates formed a loose mass consisting of small dense substructures. The overexpressed MUOdC and MUO, on the other hand, formed other types of aggregates which were distributed in the cytoplasm. They consisted of tubular and circular membrane structures, which were morphologically confirmed to be derived from the endoplasmic reticulum (ER). No immunolabeling signals for MUOdC and MUO were present free in the cytoplasm and most of them were associated with membrane structures, suggesting that overexpressed UO containing the MTS attached to the ER membranes soon after synthesis and segregated from the cytosolic compartment. All the UO aggregates were stained for ubiquitin antigen. Pulse-chase experiments in combination with proteasome inhibitors suggested that proteasomes did not contribute to the degradation of these products. PMID- 11201605 TI - Dual enhancement of double immunofluorescent signals by CARD: participation of ubiquitin during formation of neurofibrillary tangles. AB - Amplification with catalyzed reporter deposition (CARD) greatly enhances peroxidase signals, which has been utilized to amplify immunohistochemical labelings including fluorochromes. Here we describe a strategy to amplify each of two immunofluorescent signals without crosstalk on double-stained histological sections from human autopsied brains with Alzheimer's disease (AD). One of the two primary antibodies (anti-Abeta or anti-PHF-tau) was probed by a species specific secondary antibody conjugated with horseradish peroxidase (HRP), which was visualized by FITC-labeled tyramide. After inactivation of HRP, the other primary antibody was probed by another species-specific secondary antibody conjugated with HRP. Amplification with biotinylated tyramide was followed by streptavidin-conjugated Cy-5, which specifically labeled the latter epitope. It was found that Abeta and PHF-tau were localized to senile plaques and neurofibrillary tangles (NFTs), respectively, which verified lack of crosstalk on the double-stained section. Localization of ubiquitin and PHF-tau was looked for at higher magnification in NFT-bearing neurons. Although these two epitopes were colocalized in some neurons, ubiquitin was not always present in PHF-tau positive NFTs. Discrepancy between PFH-tau and ubiquitin, verified inter- and intracellularly, may represent different stages of NFT formation. This is the first report of successful CARD amplification of two different fluorescent signals on double-labeling immunohistochemistry, which is now proved to be powerful in detecting epitopes in relation to AD-related lesions. Improved intensity over tenfold of the two fluorescent signals without crosstalk will expand the application of the multilabeling method with fluorochromes. PMID- 11201606 TI - Immunohistochemical study of NGF and its receptors in the synovial membrane of the ankle joint of adjuvant-induced arthritic rats. AB - To study the role of nerve growth factor (NGF) in local inflammation, we investigated the expression of NGF and its receptors, trkA and p75, in the ankle joints of adjuvant-induced arthritic rats. Infiltrated mononuclear cells revealed a positive immunoreactivity for NGF and trkA; they were also positive for immunostaining for W3/25 and ED1, which mainly stain T cells and macrophages, respectively. Changes in the ratios of NGF-positive cells to mononuclear cells showed a relatively similar pattern for trkA-positive cells, which peaked at weeks 2 to 3 after the adjuvant injection. In double-immunofluorescence staining, 80% and 65% of NGF-positive cells stained for W3/25 and ED1, respectively. Similarly, 67% and 80% of trkA-positive cells also corresponded to W3/25- and ED1 positive cells, respectively. However, p75 immunoreactivity localized on the nerve fibers but not on the cells of the ankle joints. Dense meshworks of p75 positive nerve fibers with numerous terminal varicosities were observed at weeks 2 to 4. The present findings suggest that infiltrated mononuclear cells may secrete NGF in an autocrine or paracrine manner in the inflamed synovium. An upregulation of NGF in these mononuclear cells and an increase in density of the synovial nerve fibers may be involved in the development of adjuvant arthritis in rats. PMID- 11201607 TI - Immunohistochemical evaluation of endomannosidase distribution in rat tissues: evidence for cell type-specific expression. AB - Asparagine-linked oligosaccharides of glycoproteins are subject to a series of trimming reactions by glucosidases and mannosidases in the endoplasmic reticulum which result in the removal of all three glucose residues and several of the nine mannose residues. At present, endomannosidase represents the only processing enzyme which cleaves internally and provides an alternate deglucosylation pathway. However, in contrast to the endoplasmic reticulum residential proteins glucosidase I and II, endomannosidase is primarily situated in the Golgi apparatus of rat liver hepatocytes and hepatocyte cell lines. We have performed a confocal immunohistochemical study to investigate endomannosidase in various rat tissues and used a monoclonal antibody against Golgi mannosidase II as a marker for the Golgi apparatus. Although immunofluorescence for both endomannosidase and Golgi mannosidase II was detectable in the epithelia of many tissues, renal proximal tubular cells, cortex and medulla of adrenal gland, gastric mucosa, and Leydig cells of testis were unreactive for endomannosidase. Furthermore, the endothelia in all studied tissues were unreactive for endomannosidase but positive for Golgi mannosidase II. It is concluded that by immunohistochemistry endomannosidase exhibits a cell type-specific expression in rat tissues. PMID- 11201609 TI - Age-related appearance of tubular aggregates in the skeletal muscle of almost all male inbred mice. AB - Tubular aggregates (TAs) which have been recently observed in a few mouse myopathies are identical to those described in human diseases. In this study we show that TAs are also found in the skeletal muscle of almost all normal inbred mice strains. In these inbred strains of mice the presence of TAs is shown to be related to both age and sex. Nine different muscles were stained with the modified Gomori trichrome method to reveal the general morphology of the muscles. Anti-SERCA1 ATPase was used to confirm that the TAs were in fact accumulations of sarcoplasmic reticulum and anti-MyHC IIB to demonstrate that these accumulations were found exclusively in the type IIB muscle fibers. An ultrastructural study confirmed the observations revealed by light microscopy that the TAs were derived from the sarcoplasmic reticulum. TAs were never observed in female inbred mice and were only found in type IIB glycolytic muscle fibers of male inbred mice. Therefore when analyzing the effect of genetic knock out and knock in experiments on the muscle phenotype of transgenic mice one should be aware that the presence of these aggregates is a non-specific phenomenon induced by inbreeding. PMID- 11201608 TI - Localization of hepatocyte growth factor activator inhibitor type 1 in Langhans' cells of human placenta. AB - Activation of hepatocyte growth factor (HGF) is a crucial limiting step in HGF induced signaling pathway. The HGF activator inhibitor type 1 (HAI-1) was identified as a potent inhibitor of HGF activator (HGFA), a serine proteinase that is responsible for the activation of HGF in vivo. HAI-1 is an integral membrane Kunitz-type serine proteinase inhibitor, and its mRNA has been reported to be most abundant in the placenta. In this report, specific antibody to HAI-1 was used in an immunohistochemical procedure to determine the localization of HAI I in human placenta. HAI-1 was expressed in cytotrophoblasts (Langhans' cells) of the double-layered trophoblastic epithelium of chorionic villi tissue, and syncytiotrophoblasts were almost negative. On the other hand, extravillous trophoblasts of cytotrophoblastic columns showed markedly decreased immunoreactivity, and those infiltrating into the superficial decidua membrane of early placenta were hardly stainable. The amnionic epithelial cells were also immunostained intensely. The presence of HAI-1 mRNA was also confirmed in a cultured human cytotrophoblastic cell line. In addition to HAI-1, low but distinct expression of HGFA mRNA was observed in the placenta tissue and cultured cytotrophoblasts by using a sensitive RT-PCR method. Since HGF plays an essential role in the placenta development, expression of HAI-1 and HGFA may have an important regulatory role in the placenta. The localization of HAI-I in the proliferating trophoblastic stem cells (Langhans' cells), but not in syncytiotrophoblasts and extravillous trophoblasts, suggest a possible role of HAI-1 in the proliferation of trophoblasts. PMID- 11201610 TI - Expression of CD44 isoforms in normal salivary gland tissue: an immunohistochemical and ultrastructural study. AB - We studied the expression of CD44 isoforms immunoreactivity in normal human salivary gland tissue, aiming at its full characterisation in normal epithelial and myoepithelial cell types. Optical immunohistochemistry techniques using monoclonal antibodies anti-CD44v3, CD44v4/5 and, for CD44v6, together with immunoelectron microscopy, were performed in serous, seromucinous and mucinous glands. Normal human breast and a case of lactating breast adenoma were used for comparative purposes and as controls. CD44v3 was positive in acinar and myoepithelial cells and was absent in mucin-producing cells from the different gland types. CD44v4/5 was consistently negative in all types of salivary tissue. CD44v6 was constantly positive in serous acinar cells, focally positive in basal cells of ducts, and myoepithelial cells consistently expressed it. At the ultrastructural level, CD44v6 was localised to the interdigitating processes of acinar cells, whenever they were not covered by basal lamina and to the cell membrane facing myoepithelial cells. In myoepithelial cells, immunolabelling was found at the membranes facing the acinar cells and in caveolae present at this interface. No labelling was found at cell membranes of both acinar and myoepithelial cells in contact with basal lamina or at the luminal aspect of the former. The finding of CD44v3 and v6 in myoepithelium of normal salivary glands may argue in favour of the role of these molecules in the regulation of growth and renewal of normal tissues and, potentially, on the morphogenesis of salivary gland neoplasms. PMID- 11201611 TI - Signal enhancement at the electron microscopic level using Nanogold and gold based autometallography. AB - Immunoelectron microscopy using ultrasmall gold markers is a very sensitive method to detect molecules at high resolution. In order to discriminate the gold particles in the electron microscope, enlargement of gold particles is necessary. So far, mostly silver ions were used for deposition onto the surface of gold grains. In our study, we tested the selective deposition of gold instead of silver ions to enlarge gold particles. This was performed following immunogold detection of DNA at the surface of ultrathin sections embedded in the acrylic resin LR White (postembedding approach). Morphometric analysis of the distribution of DNA in human spermatocytes revealed that the method offers very good specificity and sensitivity and therefore is a good alternative to the use of silver for signal enhancement. This technique was also applied to the detection of ribosomal genes in human testis at the electron microscopic level by in situ hybridization. Ribosomal genes were localized in peri- and intranucleolar chromatin as well as in the dense fibrillar component of nucleoli. PMID- 11201613 TI - The year 2000 in histochemistry and cell biology. PMID- 11201612 TI - Effects of ATP on intracellular calcium dynamics of the perineurium of peripheral nerve bundles. AB - Adenosine-5'-triphosphate (ATP) released from damaged cells can affect functions of adjacent cells. Injuries of peripheral tissue stimulate nerves, but effect of ATP on the nerve bundles is still speculative. Peripheral nerves are surrounded by perineurium, therefore the response of perineurium may be a first event of nerve stimulation at tissue injuries. The aim of the present study is to clarify whether the perineurium responds to ATP. To this end, we analyzed the dynamics of the intracellular calcium concentration ([Ca2+]i) of perineurial cells by confocal microscopy. ATP induced a [Ca2+]i increase of perineurial cells. Ca2+ channel blockers and removing of extracellular Ca2+, but not thapsigargin pretreatment, abolished ATP-induced [Ca2+]i dynamics. This indicated that the [Ca2+]i increase was due to an influx of extracellular Ca2+. Adenosine-5' diphosphate also elicited an increase of [Ca2+]i, but P1 receptor agonists had few effects on [Ca2+]i dynamics. Suramin (an antagonist of P2X and P2Y receptors) totally inhibited ATP-induced [Ca2+]i dynamics, but reactive blue 2 (a P2Y receptor antagonist) did not. Uridine-5'-triphosphate (a P2Y receptor agonist) induced no significant change in [Ca2+]i, but alpha,beta-methylene ATP (a P2X receptor agonist) caused a [Ca2+]i increase. In conclusion, perineurial cells respond to extracellular ATP mainly via P2X receptors. PMID- 11201614 TI - Optimizing results of esophageal resection for benign and malignant disease. PMID- 11201615 TI - Reducing the use of restraints in a rural hospital. PMID- 11201616 TI - The one hundred greatest physicians of the twentieth century. PMID- 11201617 TI - Open letter to the medical community and the Kentucky State Legislature. PMID- 11201618 TI - Diagnosing alpha 1-antitrypsin deficiency. AB - Alpha 1-antitrypsin deficiency is a genetically transmitted disorder associated with an increased risk of emphysema and liver disease. The highest incidence occurs in whites of Northern European descent; the disorder affects between 70,000 and 100,000 individuals in the United States. Most persons with alpha 1 antitrypsin deficiency are misdiagnosed or undiagnosed. The laboratory tests used to screen for and diagnose the disorder are simple, inexpensive, and provide an opportunity to prevent the development of clinical disease through education about cofactor avoidance. This article provides a review of the epidemiology, genetics, and clinical presentation of this disorder. PMID- 11201620 TI - [94th French Congress of Urology. Paris, 15-19 November 2000. Abstracts]. PMID- 11201619 TI - Avoiding Medicare fraud. Part 1. AB - In 1997, Congress authorized payments to nurse practitioners (NPs) for Medicare provided services. NP services are now reimbursed at 85% of the physician fee schedule. As this source of reimbursement was realized, so was a new area of liability for NPs. Failure to follow billing rules can result in payment denial, repayment of fees already paid, mandated educational activities, fines, fraud prosecution, loss of Medicare-billing ability, and loss of employment. Appropriate billing entails adhering to guidelines for selecting procedure codes and proper medical documentation. This article identifies high-risk areas for NPs who bill Medicare and provides resources for accessing additional information. PMID- 11201621 TI - Current status of rehabilitation, especially in patients with stroke, in Japan. AB - The current status of stroke rehabilitation in Japan was reviewed from the perspectives of epidemiology, structures, outcomes and research. Japan is the fastest aging society in the world, facing a rapid increase in its disabled population and ensuing healthcare costs. Although its mortality is decreasing, stroke is the most frequent cause of disability. Traditionally, stroke patients acutely admitted to general hospitals remained bed-ridden for months, hindering maximal functional gain. With more attention to the importance of rehabilitation, improved outcomes such as shorter length of stay, more functional gain and increased community discharge have resulted. Japan's healthcare system, characterized by universal coverage, equity and a mandatory fee schedule, has contributed to the world's longest life expectancy and the lowest infant mortality rate, but it has also lacked quality assurance. Under stringent economic conditions, drastic healthcare and welfare reform plans are being debated and pressure is mounting for more efficient stroke rehabilitation. PMID- 11201622 TI - Muscle performance in an urban population sample of 40- to 79-year-old men and women. AB - An urban population sample of 40 to 79-year-old men and women was investigated to evaluate the influence of age and activity level on muscle strength and endurance and to establish a reference material. During the investigation 144 persons were tested bilaterally, except for ankle strength, when only the right side was examined. Isometric muscle strength was determined in the knee extensors and flexors. Isokinetic (at 60 degrees/s and at 180 degrees/s) muscle strength was determined concentrically and eccentrically in the knee extensors and flexors. The dynamic and static endurance of the extensors was measured. Isometric strength was determined in the ankle plantar and dorsiflexor muscles. Isokinetic ankle plantar flexion strength was determined concentrically at 60 degrees/s with and without prior eccentric muscle contraction. Hand-grip strength was evaluated with a dynamometer. Walking velocity and the number of heel-rises were recorded. Physical activity level was assessed by questionnaire. Muscle biopsies were taken from the vastus lateralis muscle for histochemical and enzymatic analyses. Walking and the different muscle tests declined with age, and with a slight gender difference. Muscle biopsies showed a trend toward smaller muscle fibers with age. The results of our study can be used as reference material for clinical studies in different age groups. PMID- 11201623 TI - Changes in balance performance in physically active elderly people aged 73-80. AB - In our hospital in 1989 a series of 30 healthy elderly people participated in a study to evaluate the effect of physical training on improving balance. Thereafter, the majority of the people in this group continued with some kind of balance training. Seven years later we followed up 17 of the people who had participated in the original study. We wanted to evaluate the balance performance of these physically active elderly people (mean age 80.5 years) and compare it with their balance performance 7 years previously. Balance was found to be significantly impaired compared with 1989 in four out of six static balance tests. The time required to walk 30 m had increased significantly. The subjective ratings of vertigo and balance problems had not changed significantly, neither had the number of correct steps when walking forwards on one line and backwards between two lines. In dynamic posturography, the test with sway-referenced visual cues showed improved postural control, but no change in sway was seen in the other five sensory conditions. When sudden backward translations of the platform occurred, increased latencies of force response were seen. PMID- 11201624 TI - Use of healthcare, impact on family caregivers and patient satisfaction of rehabilitation at home after stroke in southwest Stockholm. AB - We previously conducted a randomized controlled trial in which early supported discharge from the Department of Neurology at Huddinge Hospital in southwest Stockholm with continuity of rehabilitation at home (n = 41) was compared to routine rehabilitation services (n = 40) for moderately disabled selected stroke patients. No statistical significant differences were found in patient outcome at 3 or 6 months, but a moderately positive effect in the home rehabilitation group was suggested. In the present study we evaluated resource utilization of health and social care, impact on family caregivers during 6 months after acute stroke and patient satisfaction. A 50% reduction in total hospitalization (initial and recurrent) was observed, from 30 days in the routine rehabilitation group to 15 days in the home rehabilitation group (p < 0.001). After discharge, the mean number of home visits in the home rehabilitation group was 12. In total, the routine rehabilitation group had a higher frequency of therapy contacts and daycare in outpatient care. Seventy-eight percent received help from a family caregiver in activities of daily living, yet only 15% had formal home help service. No major differences were found in use of home help service or impact on family caregivers in the form of time devoted to helping the patient or subjective well-being of spouses as per Sickness Impact Profile. Patient satisfaction was in favour of the home rehabilitation group, but a significant difference was only found in active participation in rehabilitation programme planning. In conclusion, early supported discharge with continuity of rehabilitation at home, using goal-directed functional activities based on the patient's personal interests, should be the rehabilitation service of choice for moderately disabled stroke patients fulfilling certain criteria, provided that further evaluation during the first year after stroke reveals no great changes in outcome or resource use. More research into the effectiveness and cost implications of early supported discharge with continuity of rehabilitation at home is needed in other parts of Sweden and in other countries before it can be asserted that the conclusions drawn from this study are applicable elsewhere. PMID- 11201625 TI - Feasibility of, and success in adopting a low-fat diet in coronary patients. AB - The aim of this study was to evaluate the feasibility of dietary counselling and the predictability of success in reducing fat intake to less than 20% of total energy in patients with symptomatic coronary heart disease. Forty-seven patients with coronary heart disease attended a 2-week in-house cardiac rehabilitation course with the main emphasis on individual dietary counselling by a nutritionist. Patients were followed up at 3 and 6 months. The dietary data were collected by means of 3-7 days food diaries. Mean fat intake decreased from 33.6 +/- 6.2% to 24.7 +/- 5.5% of total energy intake at 3 months and to 27.0 +/- 6.9% (p < 0.001) at 6 months. Only 13% of the patients were able to reduce their dietary fat intake as recommended. Thus, reduction of > or = 20% was considered a good response, while reduction of < 20% was classified as poor. Forty-seven percent (n = 22) of the patients were good and 53% (n = 25) poor responders. It was not possible to predict the success rate from the baseline data. After a 2 week intensive counselling period at the rehabilitation centre, half of the coronary patients were able to comply with a low-fat diet at home for 6 months. Long-term compliance requires further investigation. PMID- 11201626 TI - Validity of ambulatory accelerometry to quantify physical activity in heart failure. AB - The purpose was to assess the validity of a novel Activity Monitor to quantify physical activity in congestive heart failure. The Activity Monitor is based on long-term ambulatory monitoring of signals from body-fixed accelerometers. Information can be obtained on which mobility-related activity is performed, when, how intense, and for how long. Ten patients performed several functional activities. Continuous registrations of accelerometer signals were made and the output was compared with visual analysis of simultaneously made video recordings (reference method). Overall results showed an agreement between both methods of 90%. Percentages of sensitivity and predictive value were higher than 80% for most activities. Overall number of transitions was determined well (Activity Monitor, 153; video, 149; p = 0.33). It was concluded that the Activity Monitor is a valid instrument to quantify several aspects of everyday physical activity in congestive heart failure. PMID- 11201628 TI - Thrombolysis in acute myocardial infarction. Present challenges. PMID- 11201627 TI - Thrombolytic therapy impact on prognosis after twelve months of first acute myocardial infarction. AB - INTRODUCTION AND OBJECTIVES: Thrombolytic therapy is still widely used to restore antegrade flow in the infarct related artery (IRA), with unquestionable benefits in mortality reduction of such patients. The aim of this study was to evaluate early (< or = 28 days) and one-year mortality of patients with a first Q wave myocardial infarction (Q AMI), comparing those who underwent thrombolytic therapy with those who did not. POPULATION AND METHODS: A retrospective study was done on 907 patients (median age: 35 +/- 13 years, 66% male) admitted to a Coronary Unit with the diagnosis of first Q AMI, from January 1988 to December 1997, all in the same geographical area (minimum follow-up period of one year, mean follow-up 43 +/- 37 months). We compared demographics and clinical characteristics (coronary risk factors, previous history of angina, MI location and evolution, cardiac events, 28 day and one-year mortality) of patients who underwent thrombolysis (group T = 355) versus those who did not undergo reperfusion therapy (group NT = 552). RESULTS: Of these patients 39% underwent thrombolytic therapy. Group NT had a greater number of female patients (40% vs 25%; p < 0.001), a significantly higher mean age (67 +/- 12.2 vs 61 +/- 12; p < 0.001), and a higher percentage of diabetics (29% vs 19%; p < 0.001), in comparison to group T. The Q AMI developed into Killip class > or = 2 in 43% of patients in group NT and 23% in group T (p < 0.001). A higher number of AV block (NT-13% vs T-8%; p < 0.05) and higher in hospital mortality (NT-14% vs T-9%; p < 0.05) was observed in patients not undergoing thrombolysis. The early (NT-22% vs T-12%; p < 0.001) and one-year (NT 33% vs T-16%; p < 0.001) mortalities were significantly higher in group NT than in group T, even after multivariate analysis. CONCLUSIONS: 1--Patients who did not undergo thrombolytic therapy initially had a profile of greater severity, and a higher early and one-year mortality rate. 2--Those who underwent thrombolytic therapy presented a significantly lower mortality, a benefit that was still observed after one year of follow-up and after multivariate correction. PMID- 11201629 TI - LDL peroxidation in adolescent female gymnasts. AB - Physical exercise may in vivo promote an increase of free radical formation. Low density lipoproteins (LDL) are highly susceptible to oxidation, probably because of their high polyunsaturated fatty acid content, since lipid oxidation is an important factor in the genesis and development of atherosclerosis. The aim of the present study is to evaluate the effect in a group of adolescent gymnasts, of intense and regular physical exercise on lipid profile and redox status. POPULATION: All members of the Portuguese National Team of Rhythm Gymnastics (1996) (n = 20). METHODS: 1. Clinical evaluation 1.1 Anthropometric evaluation: weight, height, triceps, biceps, subscapular and supra- and supra-iliac skinfolds. NCHS were used as the standard of reference for weight and height, and Frisancho for the sum of skinfolds; 1.2. Evaluation of nutritional status (Quetelet body mass index) and body composition (Durnin and Siri). 2. Evaluation of biological parameters: a blood sample was collected after 12 hours fasting and 24 hours detraining, to evaluate: 2.1 Lipid profile: total cholesterol, high (HDL) and low (LDL) density lipoproteins, triglycerides, apolipoproteins A1 and B, were measured using internationally recommended laboratory methods; 2.2. Plasma trace elements: zinc, copper and selenium, by atomic absorption; 2.3 Red blood cell enzymes; transmembranar reductase (TMR), metahemoglobin reductase (MethaHbRed) and acid phosphatase, by spectrophotometry; 2.4. Redox status: MDA and MDA-LDL were evaluated by spectrophotometry. 3. Evaluation of eating habits: 24 hr recall. RESULTS: Chronological age is 14.3 +/- 1.7 years. Nutritional assessment shows a mean value for height near the 50th percentile (99% +/- 3.8), and low mean values respectively for BMI (89.3% +/- 9) and sum of triceps and subscapular skinfolds (51.9% +/- 14). Study of lipid profile shows low mean values for total cholesterol (162.3 mg/dl +/- 27.7) LDL-cholesterol (87.6 mg/dl +/- 22.6) and Apo B (64.4 mg/dl +/- 11.5), but high values for HDL-cholesterol (61.3 mg/dl +/- 14.5) and Apo A1 (173.1 mg/dl +/- 25.1). We observe higher values for total cholesterol and LDL-cholesterol in those with lower Cu plasmatic levels. We also observe a negative significative correlation between MDA-LDL and Zn (r = -0.469), Cu (r = -0.524) and RTM (r = -0.608). CONCLUSIONS: The AA concluded that in this group of gymnasts intense physical exercise induces, a favorable lipid profile, but a clear susceptibility to LDL peroxidation in those with lower plasma Cu and Zn values. It is possible that the negative correlation observed between MDA-LDL and TMR is caused by higher consumption of TMR induced by the action of exercise on the oxidative system. PMID- 11201630 TI - Permanent pacing in patients with congenital atrio-ventricular block--experience of 33 cases. AB - OBJECTIVES: The authors review permanent pacing in patients with congenital atrioventricular block (CAVB) and present their experience in permanent pacing in this pathology. STUDY POPULATION AND METHODS: In a population of 4,355 patients submitted to implantation of permanent pacing between January 1980 and January 1998, 33 (0.75%) had CAVB. The mean age of the patient population with CAVB was 16.7 years (aged from eleven days to 35 years); 33% were below 10 years of age; 16 patients were male. The majority of the patients had symptoms of brain hypoperfusion; two patients had concomitant malignant ventricular tachyarrythmias (one of these with Torsade de Pointes due to congenital long QT syndrome). Transvenous (endocardial) pacing was used in 32 patients (two with previous epicardial pacing and exit block) and epicardial pacing in one. The mode of stimulation used was VVI in three patients, DDD in eight patients, VVIR in 14 patients, DDDR in four patients and VDD in four. Smaller pulse generators were used in children of lower weight. In recent years single lead VDD systems have been preferred whenever technically possible. Vascular access was the left cephalic vein in 17 patients; the left subclavian vein in 14 patients and the right jugular vein in one patient. During a mean follow-up of 6.9 years, two patients with ventricular stimulation systems developed "Pacemaker Syndrome" and required a change of mode of stimulation. Lead fracture and posterior cutaneous necroses were observed in two other patients, who were accordingly submitted to surgical revision. It was deemed necessary, one year later, to increase the lead loop in a child with a permanent pacemaker implanted at eleven days of age. No other complications occurred with the other patients; replacement of the pulse generators was performed in an elective manner. CONCLUSIONS: CAVB is a rare indication for the implantation of a permanent pacemaker. In children, in the majority of cases, endocardial stimulation is possible in spite of the obvious technical difficulties due to low weight. Sequential, more physiological, stimulation systems should be preferred. However, VVIR stimulation systems of smaller dimensions can be the first choice of mode of stimulation in smaller children, mainly due to anatomical and technical limitations. PMID- 11201631 TI - Determinants of in-hospital mortality in women with acute myocardial infarction who underwent primary coronary angioplasty. AB - INTRODUCTION: According to recent data, women have a greater risk of dying from an acute coronary event. The determinants of this ominous prognosis are not completely understood. Preliminary analysis of our data suggested that this poorer prognosis is also observed in the subgroup of patients with acute myocardial infarction submitted to direct coronary angioplasty (PTCA). This finding prompted us to investigate gender differences and their determinants in this particular context. OBJECTIVE: To identify risk factors associated with the greater in-hospital mortality of women with acute infarction who underwent PTCA. METHODS: One hundred and forty-five consecutive patients with acute myocardial infarction who underwent direct PTCA in the same hospital were studied retrospectively. Data were collected from the database of the catheterisation laboratory and from clinical files. The following parameters were analysed: in hospital mortality, age, prevalence of diabetes mellitus, history of coronary heart disease, time elapsed from beginning of symptoms to coronary intervention, peak values of CK and MB-CK, number of coronary arteries with significant disease at angiography, culprit lesion localisation, and prevalence of shock on admission. For statistical analysis, cross-tabulation (Pearson x2) and comparison of means (Student's t test) were employed when appropriate; an error of 5% was admitted for the rejection of the null hypothesis. RESULTS: Women (n = 39) represented 26.9% of sample. In hospital mortality was 28.2% (n = 11) for women and 11.3% (n = 12) for men (p = 0.014). The prevalence of coronary heart disease before the current acute event, the time elapsed from beginning of symptoms to coronary intervention, and maximum values of CK and MB-CK were similar in both genders. Differences between women and men were found as regards the following variables (women vs men): age (61.7 +/- 10 vs 56.1 +/- 12.6 years), prevalence of left main disease (15.3 vs 1.9%) and prevalence of shock (41 vs 17%) and diabetes (38.7 vs 13.6%). Considering women and men who died, only disease severity as evaluated by the number of vessels involved distinguished both genders (p = 0.05). CONCLUSIONS: In our experience, women admitted with acute myocardial infarction and treated by direct PTCA are, on average, older than men and have a greater prevalence of shock at admission, of left main disease and of diabetes, and more severe coronary artery disease. In the present series and as regard in hospital mortality, disease severity as evaluated by the number of vessels involved is the only variable that discriminates women from men. PMID- 11201632 TI - Reversible sympathetic vasomotor dysfunction in POTS patients. AB - BACKGROUND: Orthostatic intolerance refers to the development upon assuming an upright posture of disabling symptoms, which are partly relieved by resuming the supine position. Postural tachycardia syndrome (POTS) is an orthostatic intolerance syndrome characterized by palpitations due to excessive orthostatic sinus tachycardia, lightheadedness, tremor, and near-syncope. Patients usually undergo extensive medical, cardiac, endocrine, neurological and psychiatric evaluation, which usually fails to identify a specific abnormality. We investigated the autonomic and hemodynamic profile of POTS patients and the efficacy of bisoprolol and or fludrocortisone. METHODS AND RESULTS: We evaluated eleven female patients with POTS before and after medical treatment with a cardio selective beta blocker (bisoprolol) and/or fludrocortisone, and eleven age matched controls. Variability of heart rate and systolic blood pressure was assessed by Fast Fourier Transform, and spontaneous baroreceptor gain by temporal sequences slope and alpha index. Modelflow was used to quantify hemodynamics. All patients improved greatly after medication. The autonomic and hemodynamic impairment observed in patients with POTS, particularly after orthostatic stress, is treated effectively with bisoprolol and/or fludrocortisone. These results need further confirmation in a controlled double-blind study. CONCLUSIONS: Proper medical treatment dramatically improves the clinical and autonomic/hemodynamic disturbances observed in patients with POTS. The data support the hypothesis that POTS is due to a hyperadrenergic activation and/or hypovolemia during orthostasis. PMID- 11201633 TI - [The Cochrane Collaboration and the practice of evidence-based cardiology]. AB - Evidence-based Cardiology (EBC) permits a rational and updated clinical approach to patients. The EBC practice needs credible, independent and scientifically solid information, but the sheer volume of the medical bibliography precludes individual solutions: we have too much information and what is relevant is sunk within what is irrelevant or useless. Selection, critical appraisal and synthesis of the best scientific evidence constitutes the basis of EBC. The Cochrane Collaboration is the best source of independent, updated and valid information: through published systematic reviews, the evidence is available in the format of CD-ROM, and can serve as the basis for a modern, efficient and rational cardiological practice. PMID- 11201634 TI - [Portuguese Association of Arrhythmology, Pacing and Electrophysiology (APAPE). National Registry of Interventional Electrophysiology for 1999]. AB - Based on data supplied by the centres that execute Interventional Electrophysiology in Portugal, the authors performed a survey of the electrophysiological studies, with or without associated catheter ablation. This report quantifies the experience of all centres, as well as with different classes of ablation techniques. Furthermore, the authors performed a survey of implanted cardiovertor defibrillators, distinguishing their distribution among the different centres. They conclude that the number of centres that practice Interventional Arrhythmias in Portugal is continuously increasing, as well as the number of catheter ablations performed, although these rates have somewhat stabilised in the last year. The number of implanted cardiovertor defibrillators has also grown yearly since 1992, with a 24% increase last year, but is not yet close to the European average of implants per million of inhabitants. PMID- 11201635 TI - Mitral valve fenestration. PMID- 11201636 TI - Noncontiguous spinal metastases and plasmocytomas should be operated on through a single posterior midline approach, and circumferential decompression should be performed with individualized reconstruction. AB - BACKGROUND: In noncontiguous spinal metastatic disease, anterior or combined anterior-posterior surgery is an effective treatment. The objective of this study is to investigate whether circumferential decompression through a single-stage posterior midline approach with individualized spinal reconstruction can still achieve comparable results for functional improvement and for maintenance of spinal alignment in the absence of the risks associated with the more invasive transcavitary or combined approaches. METHOD: Seventeen patients with noncontiguous spinal metastases and plasmocytomas at one or two adjacent levels were included in this series. Circumferential decompression was obtained with anterior reconstruction and posterior fixation in ten patients, and with posterior instrumentation alone in seven patients. Postoperatively the patients were prospectively followed, and their functional status and spinal alignment were periodically evaluated. FINDINGS: Fourteen patients died from progression of their underlying cancer. Their mean survival time was 8 months (range: 1 to 21 months). Three survivors were evaluated at 10, 4 and 3 months respectively. At one month after surgery, 14 patients (82%) showed neurological improvement. Of 10 preoperative nonambulators, seven regained walking capacity. Five patients who were ambulatory with assistance improved to full functional independence. Local tumour recurrence was recorded in one patient after subtotal vertebrectomy for a plasmocytoma at L5. No other tumour recurrences were noted. In one patient a partial loss of correction occurred at T6 - without functional deterioration, however. Spinal alignment was maintained in all other patients who became or remained ambulatory. No major intra-operative complications or peri-operative deaths occurred. CSF leakage was recorded as the most common complication in four patients. INTERPRETATION: Circumferential decompression and spinal reconstruction through a single-stage posterior midline approach is feasible and effective. The extent of surgery can be individualized by means of this technique to the patient's specific problem. In patients with limited life expectancy from metastatic neoplastic disease, the results compare favourably with the more invasive anterior or combined antero-posterior procedures. PMID- 11201637 TI - Animal model for cerebral arteriovenous malformation. AB - BACKGROUND: The present study was conducted to establish an animal model for the investigation of the pathophysiology and haemodynamics of cerebral arteriovenous malformation (AVM) but also to assess therapeutic aspects. METHOD: For anatomic and haemodynamic reasons, dogs were chosen as the animal model. An arteriovenous fistula was created by interposing a segment of the superficial temporal artery between one of the main branches of the middle cerebral artery and the dorsal sagittal sinus. A temporal muscle graft supplied by this artery was implanted intracerebrally in the ischaemic area. FINDINGS: The angiographic and histopathologic findings obtained in the animal model are comparable with the situation found in intracerebral AVM in humans. INTERPRETATION: The animal model of intracerebral AVM established in this study allows for further investigation of the pathophysiology and dynamics of this disorder. It may help to develop better therapeutic options and thus improve the prognosis of affected patients. PMID- 11201638 TI - Statistical analysis of factors affecting the outcome of patients with ruptured distal anterior cerebral artery aneurysms. AB - The clinical factors affecting the outcome of patients with ruptured distal anterior cerebral artery (ACA) aneurysms were analyzed using multiple logistic regression analysis. The medical records were reviewed of 52 patients (57 aneurysms) with ruptured distal ACA aneurysms operated on by the same neurosurgeon over 25 years. The standard policy was early surgery for patients in Hunt and Kosnik grades I to IV. Age, sex, Hunt and Kosnik grade, timing of operation, size of aneurysms, number of aneurysms, association of intracerebral haemorrhage (ICH), intraventricular haemorrhage, and azygos ACA, use of temporary clipping, occurrence of premature rupture, and presence of psychiatric change were investigated. Univariant analysis disclosed that clinical grade (P = 0.0006), size of aneurysm (P = 0.005), and size of ICH (P = 0.012) affected the outcome of patients. Multiple logistic regression analysis found that Hunt and Kosnik grade (P = 0.010) and timing of operation (P = 0.033) affected the outcome. There was no significant relationship between long-term outcome and clinical factors, although a close relationship was found with Hunt and Kosnik grade (P = 0.071). Clinical grade and timing of the operation affected the outcome of patients with ruptured distal ACA aneurysms. Patients harboring ICH of over 3 cm diameter in poor grades should also be carefully treated. PMID- 11201639 TI - Early experiences of haemostasis on brain tumour surgery with Argon Plasma Coagulation (APC). AB - OBJECTIVE: We first applied a novel haemostatic strategy involving Argon Plasma Coagulation (APC), an innovative no-touch electrocoagulation technique in which a high-frequency alternating current is delivered to the tissue through ionized argon gas, to brain tumour surgery, and report its usefulness and limitations. METHODS: The APC system we used comprised an APC 300 developed by ERBE Elektromedizin GmbH, Germany. We applied APC to 13 brain tumours in 12 patients (5 meningiomas, 4 sarcomas, 2 glioblastomas, and 2 pituitary adenomas). To avoid unnecessary thermal injury to the tissue as much as possible, power/gas flow settings of 20 and 40 W were used. The impact time was varied individually but was around several seconds per one impact. The argon jet (1.5-4.5 L/min) clears a field of pooled blood and evenly conducts electrical energy to the target tissue. A thin and flexible probe particularly increased the usefulness of APC for haemostasis on deep-seated skull base tumour operations under a microscope. CONCLUSION: All patients were successfully treated and satisfied with the surgical results without any complications due to APC. APC appears to be an excellent alternative strategy for achieving haemostasis on vascular-rich brain tumour surgery, and may be valuable for the management of patients with coagulation defects. PMID- 11201640 TI - The application of image fusion in stereotactic brachytherapy of brain tumours. AB - BACKGROUND: The visualization of any morphological volume (i.e. CT, MRI) together with an additional second morphological volume (i.e. CT, MRI) or functional data set, which may come from SPECT or PET, is a new method for treatment planning, verification and follow-up of interstitial irradiation. METHOD: The authors present their experience on interstitial irradiation of brain tumours with stereotactically implanted I-125 seeds supported by image fusion. The image fusion was performed by the BrainLab-Target 1.13 software on Alfa 430 (Digital) workstation before, during, and after interstitial irradiation of brain tumours with Iodine125 seeds. RESULTS AND INTERPRETATION: On the basis of 20 brachytherapeutic image fusion of stereotactic CT (slices with fiducials) with additional stereotactic CT, MRI, PET and SPECT images provides more accurate and precise target volume, more exact localization of catheters and isotope seeds (verification fusion), differentiation between the localization and amount of the necrotic and proliferating parts of the tumours and shows the volume changes in consequence of interstitial irradiation. The image fusion should help to improve the accuracy and minimize the perifocal morbidity of interstitial irradiation. PMID- 11201641 TI - Permanent postoperative anosmia: a serious complication of neurovascular decompression in the sitting position. AB - In posterior fossa surgery, the sitting position offers a number of advantages believed to outweigh complications such as air embolism and pneumatocephalus. For this reason, the sitting position is frequently used in neurovascular decompression for trigeminal neuralgia. Two years ago we reported on a previously undescribed complication: permanent postoperative anosmia. Following the recent occurrence of a second case, we conducted a nationwide survey to determine the frequency of this complication. Permanent postoperative anosmia following surgical procedures in the sitting position has been observed in 3 other institutions. In addition, the survey revealed that only 40% of German neurosurgeons still favor the sitting position for surgery of the posterior cranial fossa. Considering that permanent anosmia severely reduces quality of life, and that it can be avoided by using another position, the sitting position for surgical procedures in the posterior fossa should be restricted to special cases (e.g., brain stem tumors). PMID- 11201642 TI - A co-operative study: clinical characteristics of 334 Korean patients with moyamoya disease treated at neurosurgical institutes (1976-1994). The Korean Society for Cerebrovascular Disease. AB - A co-operative study was conducted to determine the clinical characteristics of patients with moyamoya disease who were diagnosed and treated at neurosurgical institutes in Korea before 1995. Twenty-six hospitals contributed 505 cases and among them, the clinical characteristics of 334 patients with definite moyamoya disease were evaluated. The number of patients began to increase from the late 1980s, and after that approximately 20 patients were treated each year. There were two age peaks: from six to 15 and from 31 to 40 years of age. Haemorrhagic manifestations occurred in approximately 43% of the patients. The major clinical manifestations were haemorrhage in adults (62.4%) and ischaemia in children (61.2%). Overall 54.5% of the patients experienced decreased consciousness levels, mainly due to intracranial haemorrhage or cerebral infarction. In the patients with ischemic manifestations, the adult patients were more likely to have cerebral infarction than the pediatric patients (80% vs. 39%) and the pediatric patients were more likely to have TIA (61% vs. 25%). Thirty eight percent of the patients underwent bypass surgery and 53% of these procedures were performed bilaterally. Treatment policies, including indications for bypass surgery and commonly used drugs, were somewhat different according to the institution. Overall favorable outcome was 73%, and the most significant factor affecting poor outcome was haemorrhagic manifestation. This article describes the characteristics of 334 patients with moyamoya disease, who were diagnosed and treated at neurosurgical institutes in Korea before 1995. PMID- 11201643 TI - Elevation of nitric oxide metabolites in the cerebrospinal fluid of patients with moyamoya disease. AB - BACKGROUND: To investigate whether nitric oxide (NO) contributes to formation of abnormal collateral circulation in patients with moyamoya disease. METHODS: Cerebrospinal fluid (CSF) samples were obtained from the subarachnoid space of the Sylvian fissure during combined bypass surgery for moyamoya disease and kept frozen until NO metabolites, nitrate and nitrite, were measured using a Griess method. RESULTS: Compared with control CSF obtained from 18 patients with hemifacial spasm, unruptured aneurysm, etc., concentrations of NO metabolites in 26 CSF samples of 18 patients with moyamoya disease were significantly higher (mean +/- SE; 17.6 +/- 1.2 vs. 10.5 +/- 1.0 microM, p < 0.01). In eight patients, the CSF samples from both the first and second operation could be obtained. NO metabolite concentrations (20.5 +/- 2.3 microM) in CSF obtained from the first surgery decreased to 15.7 +/- 1.8 microM (p < 0.01) in CSF obtained from the second, contralateral procedure. The cases of moyamoya disease with greater development of moyamoya vessels at angiographic stage 3 and 4 tended to show higher concentrations of NO metabolites than cases at earlier or later stages with a few moyamoya vessels. INTERPRETATION: Nitric oxide concentrations in CSF are chronically elevated in moyamoya disease, probably reflecting development of abnormal collateral circulation. i.e. moyamoya vessels. Vascular bypass surgery can reduce abnormal collateral circulation with reduced production of nitric oxide. PMID- 11201644 TI - Minor head injuries: one year experience according to the new Italian guideline. AB - BACKGROUND: The data concerning a consecutive series of 4,536 adult patients suffering from minor head injuries treated at the Department of Neurosurgery over a period of one year are reported. METHOD: The patients' age, sex and the circumstances of the injury have been taken into consideration. The patients, according to the new method, were divided into four groups. Group 0 (3,864 patients) included all patients with Glasgow Coma Scale (GCS) score 15. They did not present any clinical features such as loss of consciousness (LOC), post traumatic amnesia (PTA), headache or vomiting. No risk factors (RF) such as coagulopaties, alcoholism, drug abuse, epilepsy, previous neurological treatment or disabled elderly patients were detected. Group 1 (600 patients) included patients with GCS score 15. The patients presented one or more clinical features (LOC, PTA, headache, vomiting). No RF were presented. Group 2 (24 patients) included patients with GCS score 14 with or without clinical features (LOC, PTA, headache, vomiting) and with or without RF. Group 0-1R (48 patients) included patients with GCS score 15 with or without clinical features (LOC, PTA, headache, vomiting). All of them presented RF. The presence of focal neurological signs, open injury and GCS score < or = 13 were considered criteria for exclusion. FINDINGS: All the patients from groups 1, 0-1R, 2 and 187 patients from group 0 underwent CT scan for a total of 859 exams which are analyzed and discussed. 458 patients were admitted and are divided as follows: 216 from group 0, 192 from group 1, 26 from group 0-1R and all the 24 belonging to group 2. Six patients were treated surgically (3 extradural haematomas, 2 lobe contusions, 1 acute subdural haematoma) and one of them (0.02% of the total) died (extradural haematoma). The patients who were not admitted were sent home with an information sheet after at least a six hour observation period. INTERPRETATION: The authors draw the conclusion that they have evaluated the applicability and efficacy of guidelines, developed by the study group on head injury of the Italian Society of Neurosurgery. A critical part of our guidelines is not only to identify all the intracranial lesions, but to identify patients harbouring relevant intracranial mass before clinical deterioration. PMID- 11201645 TI - Reduction of edema and infarction by Memantine and MK-801 after focal cerebral ischaemia and reperfusion in rat. AB - N-methyl-D-aspartate (NMDA) receptor antagonists have been found to be protective after cerebral ischemia. However most of these drugs have limited value as neuroprotectives in clinical therapy because of their side effects. Memantine is a noncompetitive NMDA receptor antagonist and it has been used for the treatment of various cerebral disorders with relatively few side effects. We investigated the beneficial effects of Memantine and compared its effect with MK-801 in a temporary focal cerebral ischemia model. As cerebral ischemia model three hours middle cerebral artery occlusion (MCAO) with intraluminal thread and three hours reperfusion was used. 78 male Spraque-Dawley rats were divided into three groups as follows: Control (Saline), treatment 1 (MK-801), and treatment 2 (Memantine) groups. In the treated groups, 15 minutes after MCAO, MK-801 and Memantine were administered in amounts of 1 mg/kg and 10 mg/kg intraperitoneally respectively. After a 3 hour period of reperfusion, the animals were examined for neurological deficits and then killed. The following values were measured; cerebral water content, blood brain barrier (BBB) permeability at the core and periphery of the ischemic hemisphere and contralateral hemisphere and infarct volumes. The severity of neurological deficit (p < 0.001) and infarct volume (p < 0.001) was reduced in both Memantine and MK-801 treated groups compared with saline treated groups. Memantine attenuated brain edema formation and BBB permeability at the periphery (p < 0.01), MK-801 both at the core (p < 0.05) and the periphery (p < 0.01) of the ischemia. These results demonstrated that the NMDA receptor antagonists Memantine and MK-801 were neuroprotective when given 15 min after MCAO in temporary focal cerebral ischemia. PMID- 11201646 TI - Neuroprotective effect of melatonin on cortical impact injury in the rat. AB - The pineal hormone melatonin is a highly efficient physiological scavenger of free radicals involved in secondary brain damage. A variety of experimental studies have demonstrated a neuroprotective effect for melatonin, based on its antioxidant activity. The purpose of the present study was to investigate the time-dependency and a possible protective effect of exogenous melatonin in the cortical impact model in rats. The protective effect was quantified determining contusion volume, brain edema and brain water content. 45 anesthetized male Sprague-Dawley rats (250-350 mg) were subjected to cortical impact injury of moderate severity (7 m/s, deformation 2 mm). Melatonin (100 mg/kg bw i.p.), or a vehicle was injected 20 min before trauma, immediately after, and 1 and 2 hours after trauma during daytime and nighttime. Posttraumatic lesion volume using hematoxylin-eosin staining, hemispheric swelling, brain water content, cerebral perfusion pressure and intracranial pressure 24 hours after injury were investigated. Melatonin, given during nighttime, significantly reduced contusion volume corresponding to a mean reduction of contusion volume of 27% (placebo, n = 7: 41.9 +/- 5.2 mm3, melatonin, n = 8: 30.5 +/- 4.2 mm3, p < 0.05). Given during daytime, the reduction in contusion volume was not significant (placebo, n = 8: 42.1 +/- 5.1 mm3, melatonin, n = 8: 35.9 +/- 2.2 mm3, reduction of 15%, p = 0.08, n.s.). Hemispheric swelling was unchanged by melatonin treatment. Mean arterial blood pressure and rectal temperature remained stable before and after the cortical impact injury and injection of melatonin. This study shows that melatonin significantly reduces contusion volume with major effects during night. PMID- 11201647 TI - Amsterdam University Clinic for Neurosurgery. PMID- 11201648 TI - Spontaneous chronic and subacute subdural haematoma in young adults. AB - Spontaneous subacute and chronic haematoma in young adults is rare. It has not been previously reported in this age group. We present three cases of chronic and subacute subdural haematoma in young adults, in one of whom the diagnosis was certainly delayed. All three patients underwent burrhole evacuation and made a full neurological recovery. A cause for the haematoma was never established. The literature on the subject, which is scanty, is reviewed and the condition is briefly discussed. The aetiology remains obscure. PMID- 11201649 TI - Unusual occurrence of a pseudo-aneurysm of the middle cerebral artery in a patient with fibromuscular dysplasia. AB - Our patient is the first reported case of pseudo-aneurysm due to the rupture of an intracranial artery in the context of fibromuscular dysplasia (FMD). As we assume that our case is probably not unique, we conclude that this diagnosis may be sometimes overlooked for lack of confirmation either by surgery or autopsy. The retrospective study of the arteriograms suggests some clues that should be taken into account to foresee the existence of an intracranial pseudo-aneurysm in order to avoid unexpected peroperative difficulties: 1.) the rapid growth of the lesion within a few weeks and 2.) the unusual location of the aneurysmal neck at some distance from a arterial bifurcation. PMID- 11201650 TI - Calloso-marginal artery aneurysm missed by three angiographic studies. PMID- 11201651 TI - Retroclival arachnoid cyst presenting with spontaneous intracystic haemorrhage- case presentation. PMID- 11201652 TI - Stabilization of the unstable upper cervical spine in rheumatoid arthritis. PMID- 11201653 TI - Short course antimicrobial therapy in intracranial abscess. PMID- 11201654 TI - Histology of the hepatopancreas of the freshwater prawn Palaemonetes argentinus (Crustacea, Caridea). AB - The aim of this study is to describe the histological structure of the hepatopancreas of P. argentinus in intermoult stage in order to provide a baseline for future analysis of its modifications as indicator of environmental stress. Adults at sexual rest of both sexes were collected from Sotelo stream, tributary of Mar Chiquita lagoon, Argentina (38 degrees S 55 degrees W). P. argentinus hepatopancreas was studied by using histological techniques. The hepatopancreas is a bilaterally bilobed brown-yellowish organ. The structure is formed by a mass of blind tubules, with scarce intertubular space. Each tubule consists of a cylindrical epithelial layer surrounded by a basal lamina and myoepithelial cells. Four cellular types were recognized which represent E (embryonic), F (fibrillar), R (resorptive) and B (blisterlike) cells of other decapods. E-cells were found in mitosis and some F-cells had signs of cellular death. B-cells were observed in different phases of holocrine secretion and some groups of desquamated cells appeared at medial and proximal zones, revealing an important cellular turnover rate. According to these observations F, R and B cells are differentiated independently from E-cells. PMID- 11201656 TI - Effects of alpha-difluoromethylornithine on the Fas expression and apoptosis in Hep-2 cells. AB - DFMO is an irreversible inhibitor of ornithine decarboxilase (ODC), the key enzyme in mammalian polyamine biosynthesis, and has been shown to induce apoptosis. In this paper, the relation between the effects of DFMO on the polyamine content, apoptotic index and Fas expression in HEP-2 cells was determined. Fas is a type I membrane protein with a molecular mass of 45 kDa, which mediates apoptosis. The results suggest that the treatment with the polyamine inhibitor DFMO induced the expression of the surface antigen Fas, which could be responsible for trigger apoptosis in these cells. PMID- 11201655 TI - Further observations on cerebellar climbing fibers. A study by means of light microscopy, confocal laser scanning microscopy and scanning and transmission electron microscopy. AB - The intracortical pathways of climbing fibers were traced in several vertebrate cerebella using light microscopy, confocal laser scanning microscopy, scanning and transmission electron microscopy. They were identified as fine fibers up to 1(micron thick, with a characteristic crossing-over bifurcation pattern. Climbing fiber collaterals were tridimensionally visualized forming thin climbing fiber glomeruli in the granular layer. Confocal laser scanning microscopy revealed three types of collateral processes at the interface between granular and Purkinje cell layers. Scanning electron microscopy showed climbing fiber retrograde collaterals in the molecular layer. Asymmetric synaptic contacts of climbing fibers with Purkinje dendritic spines and stellate neuron dendrites were characterized by transmission electron microscopy. Correlative microscopy allowed us to obtain the basic three-dimensional morphological features of climbing fibers in several vertebrates and to show with more accuracy a higher degree of lateral collateralization of these fibers within the cerebellar cortex. The correlative microscopy approach provides new views in the cerebellar cortex information processing. PMID- 11201657 TI - Immuno and cytochemical localization of Trypanosoma cruzi nitric oxide synthase. AB - The localization and subcellular distribution of Trypanosoma cruzi nitric oxide synthase was investigated in epimastigote cells by immunocytochemistry at electron and light microscope level, using a polyclonal antibody to neuronal nitric oxide synthase, and also, at light microscope level, by the nicotinamide adenine dinucleotide phosphate-diaphorase histochemical reaction. The immunoreactivity was ultrastructurally localized by electron microscopy in the inner surface of cell membranes and in free cytosolic clusters in the body, flagellum and apical extreme. Light microscopy showed that immunoprecipitates, specific for the Trypanosoma cruzi nitric oxide synthase, co-localized with the formazan precipitates generated by the diaphorase reaction in the same areas identified by electron microscopy. These results, taken together with previous finding from our laboratory could help to explain the involvement of the nitric oxide transduction pathway in T. cruzi epimastigote motility. PMID- 11201658 TI - Gut mucosal immunostimulation by lactic acid bacteria. AB - The beneficial properties of lactic acid bacteria (LAB) on human health have been frequently demonstrated. The interaction of LAB with the lymphoid cells associated to the gut to activate the mucosal immune system and the mechanisms by which they can exert an adjuvant effect is still unclear, as well as if this property is common for all the LAB. We studied the influence of the oral administration of different geneous of LAB such as Lactobacillus casei, L. acidophilus, L. rhamnosus, L. delbrueckii subsp. bulgaricus, L. plantarum, Lactococcus lactis and Streptococcus thermophilus. We determined if the LAB assayed were able to stimulate the specific, the non-specific immune response (inflammatory response), or both. We demonstrated that all the bacteria assayed were able to increase the number of IgA producing cells associated to the lamina propria of small intestine. This effect was dose dependent. The increase in IgA+ producing cells was not always correlated with an increase in the CD4+ T cell number, indicating that some LAB assayed only induced clonal expansion of B cells triggered to produce IgA. Most of them, induced an increase in the number of cells involved in the inflammatory immune response. CD8+ T cell were diminished or not affected, with exception of L. plantarum that induced an increase at low dose. This fact would mean that LAB are unable to induce cytotoxicity mechanisms. We demonstrated the importance in the selection of LAB to be used as gut mucosal adjuvant. The different behaviours observed among them on the gut mucosal immune response, specially those that induce inflammatory immune response, show that not all the LAB can be used as oral adjuvant and that the beneficial effect of them can not generalized to genous or specie. The immunoadjuvant capacity would be a property of the strain assayed. PMID- 11201659 TI - Human red blood cells from prenatal hemopoiesis. Lithium flux (sodium dependent) asymmetry. AB - In red cells from umbilical cord blood it has been referred the existence of lithium fluxes (contralateral sodium dependent) asymmetry. On account of the relevancy of this transport system in some pathologies it is pertinent the study of its kinetics to relate normal with pathological states in which it is affected. Lithium fluxes--contralateral sodium dependent were determined in N ethylmaleimide treated neonatal red blood cells. Experimental data were fitted by simple Michaelis-Menten kinetics, finding Km and Vmax variables. It was shown the persistency of asymmetry. The independence of sulfhydryl groups (or the occultation of the groups involved to this inhibitor) could explain asymmetry persistence. PMID- 11201660 TI - Morphogenesis in short-term and long-term anther derived calli of Oenothera hookeri de vries. AB - Anther culture of O. hookeri on Murashige and Skoog (1962) medium supplemented with 2 mg l-1 2,4-dichlorophenoxyacetic acid and 2 mg-1 1-naphthaleneacetic acid produced callus formation. When subcultured onto medium lacking auxin, the callus regenerated through the organogenic pathway. Non-organogenic and organogenic callus was observed using histological methods after 2, 3 and 24 weeks in culture. Three types of calli were recognized: non-organogenic friable calli, organogenic friable calli with roots and organogenic hard calli with shoots. The microscopical sections showed striking differences in tissue organization among friable and compact calli. Vascular bundles were prominent in compact calli, but were not found in friable calli. Calli sections showed at light microscopy cells at two developmental stages; differentiated highly vacuolated cells and meristematic small isodiametric cells with densely stained cytoplasm. At electron microscopy level abnormal chloroplasts were present in non-organogenic calli, while chloroplasts were well developed in organogenic hard calli. Peroxisomes with paracrystalline protein bodies were abundant in both types of calli. PMID- 11201661 TI - Preliminary results on embryo rescue for circumventing hybridization barriers in Asparagus. AB - Garden asparagus, Asparagus officinalis, is reproductively isolated from a related ornamental species with potential breeding value, Asparagus densiflorus cv. Sprengeri, by pre- and post-zygotic barriers. The latter barrier operates at the endosperm level five days after pollination in A. officinalis x A. densiflorus crosses. To try to circumvent this barrier, in vitro embryo rescue using ovule and ovary cultures was tested. Controlled interspecific crosses were made and 2,032 ovules and 826 ovaries were cultured three days after pollination under various culture media and incubation conditions. Ovaries cultured for 60 days became red (similar to mature fruits), but seed formation was incomplete. Transfer of ovules to other media was necessary to promote embryo development. The interspecific embryos increased their length from 35 microns at the initiation of culture to 1,900 microns after 120 days of culture, but seedlings were not obtained. Histological studies revealed differentiation of protoderm only. The possible causes of the failure of the embryos to complete differentiation and morphogenesis are discussed. PMID- 11201662 TI - Assessment of renal toxicity by analysis of regeneration of tubular epithelium in rats given low-dose cadmium chloride or cadmium-polluted rice for 22 months. AB - To determine whether low-dose oral administration of cadmium (Cd) induces renal toxicity, six groups of female Sprague-Dawley rats were fed a diet containing low amounts of CdCl2 or Cd-polluted rice at concentrations up to 40 ppm, and were killed after 12, 18, and 22 months (experiment 1). In addition to the determination of cortical Cd levels and histopathological assessment of kidneys, labeling indices (LIs) for proliferating cell nuclear antigen (PCNA) in the renal cortical tubular epithelium of Cd-treated rats were determined as a measure of regenerative activity. For comparison, the kidneys of rats given diets containing small to large amounts of CdCl2 up to 600 ppm for 4 months were similarly examined (experiment 2). Animals in experiment 1 demonstrated spontaneous chronic nephropathy and fluctuation in the tubular PCNA LI, but these findings were not correlated with renal Cd levels at 22 months. PCNA LI on the other hand, appeared to be linked to the severity of chronic nephropathy. In experiment 2, levels of CdCl2 of 200 ppm or more clearly induced degeneration and apoptosis of proximal tubules with high correlations between renal Cd levels, PCNA LI, and the severity of tubular degeneration. The results demonstrated that, in contrast to high-dose Cd administration, treatment with 40 ppm or less for 22 months did not influence tubular regeneration as a component of nonspecific chronic nephropathy, suggesting that long-term oral administration of low levels of Cd does not injure renal tubules in female rats. PMID- 11201663 TI - Low levels of cadmium chloride alter the immunoprecipitation of corneal cadherin complex proteins. AB - The effect of cadmium chloride on the immunoprecipitation of cadherin and the associated adherens junctional proteins, alpha- and beta-catenin, was examined in isolated bullfrog (Rana catesbeiana) corneas utilizing Western blot and enhanced chemoluminescent techniques. Application of either 1.0 microM or 75.0 microM CdCl2 to the corneal endothelium for 2 h markedly decreased the immunoprecipitation of cadherins as compared to paired control corneas. Immunoprecipitation of alpha-catenin was increased in response to both doses of CdCl2, while the immunoprecipitation of beta-catenin was little changed by either cadmium dose. There is accumulating evidence that cadmium may increase epithelial paracellular permeability by interfering with cadherin complex activity at intercellular junctions. The present study suggests that inorganic cadmium in low micromolar concentrations may decrease the integrity of the corneal endothelium, at least in part through a similar mechanism involving disruption of junctional cadherin complex function. PMID- 11201664 TI - Functional Cyp2e1 is required for substantial in vivo formation of 2,5 hexanedione from n-hexane in the mouse. AB - Neurotoxicity of n-hexane is mediated by its metabolite 2,5-hexanedione (2,5-HD). Cytochrome P4502E1 (CYP2E1) has been suggested but not shown to be involved in the formation of the metabolite. An objective of the current study was to assess the essentiality of CYP2E1 for in vivo 2,5-HD formation from n-hexane. This was accomplished by comparing urinary levels of the gamma-diketone in n-hexane treated mice in which the Cyp2e1 gene has been deleted (Cyp2e1-/-) with that in n hexane-treated wild-type (Cyp2e1+/+) mice. 2,5-HD was detectable not as the free compound but as further metabolites, at levels that were comparable in both strains of mice, following a daily 200 mg/kg i.p. dose of the alkane for 10 days. Continued daily n-hexane treatment resulted in increased urinary levels of 2,5-HD metabolites in Cyp2e1+/+ but not in Cyp2e1-/- mice. Only in Cyp2e1+/+ mice and only on day 21 of n-hexane treatment was a trace level of unchanged 2,5-HD detected. 3-Hexanol was the only other n-hexane metabolite detected in the mice but its concentration was higher in Cyp2e1-/- than in Cyp2e1+/+ mice. In n-hexane treated rats, in contrast to mice, multiple metabolites of the alkane, including unchanged 2,5-HD, were detected. The results indicate that substantial in vivo formation of 2,5-HD from n-hexane in the mouse requires CYP2E1, and suggest that further detoxification of the metabolite may be very efficient in this species. PMID- 11201665 TI - Biotransformation of trichloroethylene in collagen gel sandwich cultures of rat hepatocytes. AB - The collagen gel sandwich culture of hepatocytes has been proposed as one of the most suitable culture models available for biotransformation studies of xenobiotics. It is a complex model which imitates the cascade of enzymatic events of in vivo biotransformation and allows investigation of biological endpoints under realistic conditions. The biotransformation of trichloroethylene (TRI) has been studied in this model using rat hepatocytes. Headspace gas chromatographic measurements revealed that hepatocytes, cultured for 4 days in this in vitro system, metabolised TRI into the major oxidative metabolites trichloroacetic acid (TCA) and trichloroethanol (TCE). Cultured hepatocytes were exposed either to TRI, or to TCA and TCE. Endpoints studied were albumin secretion and the cytochrome P450 (CYP)-dependent enzymatic activities ethoxyresorufin O-deethylase (EROD), pentoxyresorufin O-depentylase (PROD) and N-nitrosodimethylamine demethylase (NDMA). The results show that both the parent compound and its metabolites exert specific effects on different CYP-dependent mono-oxygenase activities, as seen in vivo. It is suggested that collagen gel sandwich cultures represent a useful in vitro model for the investigation of metabolism-linked toxicity studies. PMID- 11201666 TI - Cytochrome P450-dependent binding of 7,12-dimethylbenz[a]anthracene (DMBA) and benzo[a]pyrene (B[a]P) in murine heart, lung, and liver endothelial cells. AB - Autoradiography was used to investigate the cellular sites of irreversible binding of 3H-labelled 7,12-dimethylbenz[a]anthracene (DMBA) and benzo[a]pyrene (B[a]P) in mice. Autoradiograms obtained from solvent-extracted tape-sections revealed an even distribution of DMBA- and B[a]P-derived radioactivity in control mice lacking sites of selective binding in the tissues. In mice pretreated with a cytochrome P4501A (CYP1A) inducer, beta-naphthoflavone (BNF) or 3,3',4,4', 5 pentachlorobiphenyl (PCB 126), a noticeable accumulation of bound radioactivity was observed in the pulmonary alveolar region. Increased labelling was also observed in heart tissue of induced mice. As demonstrated by microautoradiography of tissues from CYP1A-induced mice treated with 3H-DMBA or 3H-B[a]P in vivo, irreversible binding in lung tissue was present in endothelial cells of arteries and veins, in the alveolar septal walls, and in type 2 pneumocytes. In heart tissue, binding was confined to endothelial cells of arteries, capillaries and veins. In liver, binding was found in the hepatocytes as well as in endothelial cells of the portal veins, whereas no binding was seen in endothelial cells of the sinusoids, central veins, or arteries. These findings were confirmed in vitro using 3H-DMBA-exposed precision-cut slices, indicating that reactive intermediates of DMBA and B(a)P were formed in situ. The addition of the CYP1A inhibitor ellipticine abolished binding in the target endothelial cells. Increased endothelial binding in the lungs and liver of CYP1A-induced mice was concomitant with increased 7-ethoxyresorufin O-deethylase (EROD) and DMBA hydroxylase activity. In heart, endothelial binding was positively correlated with EROD, but not with DMBA hydroxylase. The results suggest that endothelial cells may be targets for CYP-dependent activation of such toxicants as polycyclic aromatic hydrocarbons. Consequently, the possibility that chemically induced endothelial dysfunction is a risk factor in the aetiology of cardiovascular disease demands consideration. PMID- 11201668 TI - The mercapturic acid biotransformation pathway of hexachlorobenzene is not involved in the induction of splenomegaly, or skin and lung lesions in the Brown Norway rat. AB - Involvement of the mercapturic acid pathway in the induction of splenomegaly and skin and lung pathology by hexachlorobenzene (HCB) in the rat was investigated by seeking to determine whether pentachloronitrobenzene (PCNB) has the same inflammatory effects as HCB, since both compounds are directly conjugated to glutathione, and further processed into the same mercapturic acid metabolites which are excreted via the urine. Female Brown Norway (BN/SsNO1aHsd) rats at 3 to 4 weeks of age were orally exposed to diets with or without supplementation with 450 mg HCB or equimolar (467 mg) or higher (934 mg) amounts of PCNB per kilogram of diet over 4 weeks. Gross skin lesion development and body weight gains were assessed during exposure and spleen and liver weights as well as histopathologic changes in skin and lung were assessed after exposure. After 3 weeks of exposure, urinary metabolites of the mercapturic acid and oxidative biotransformation pathways were identified using high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS). Oral exposure of the rats to 450 mg/kg HCB resulted in an increase in relative spleen and liver weights as well as in the development of skin and lung pathology in the absence of overall liver toxicity. Equimolar or higher concentrations of PCNB caused none of these effects. Urinary levels of the mercapturic acid N-acetyl-S-(pentachlorophenyl) cysteine (PCP-NAC), were comparable in HCB- and PCNB-treated rats. Levels of closely related methylsulfide derivatives of PCP-NAC, also generated via the same mercapturic acid pathway, appeared to be significantly higher in PCNB- than in HCB-treated rats, whereas the reverse was true for the urinary levels of the oxidative metabolite pentachlorophenol (PCP). Thus, results indicate that metabolites of the mercapturic acid pathway are not involved in the induction of splenomegaly and skin and lung pathology caused by HCB exposure in BN rats and that the main urinary metabolite of HCB in these BN rats is PCP. Since PCP itself, as well as other cytochrome P450-derived metabolites from HCB, are not likely to be involved in the induction of splenomegaly and skin and lung pathology, it is suggested that either the parent compound HCB or as-yet unidentified non-P450-generated metabolites are involved in these inflammatory effects of HCB. PMID- 11201667 TI - Changed cellular membrane lipid composition and lipid peroxidation of kidney in rats with chronic fluorosis. AB - An animal model of chronic fluorosis was produced by subjecting Wistar rats to high doses of fluoride in drinking water for a prolonged period. Phospholipid and neutral lipid contents in rat kidney were then analyzed by high-performance liquid chromatography (HPLC), and fatty acid compositions from individual phospholipids were measured by gas chromatography. Lipid peroxidation was detected by the thiobarbituric-acid-reactive substance assay. Results showed that the total phospholipid content significantly decreased in the kidney of the rats treated with high doses of fluoride and the main species influenced were phosphatidylethanolamine (PE) and phosphatidylcholine (PC). Decreased proportions of polyunsaturated fatty acids were observed in PE and PC in kidney of fluoride treated animals compared to controls. No changes could be detected in the amounts of cholesterol and dolichol in kidneys between the rats treated with fluoride and controls. A significant decrease of ubiquinone in rat kidney was observed in the groups treated with excessive fluoride. High levels of lipid peroxidation were detected in kidney of the rats with fluorosis. It is plausible that the specific modification of lipid composition results from lipid peroxidation. The oxidative stress and modification of cellular membrane lipids may be involved in the pathogenesis of chronic fluorosis and provide a possible explanation for the gross system damage observed in the body, especially in soft tissues and organs. PMID- 11201669 TI - Cultures of exfoliated epithelial cells from different locations of the human urinary tract and the renal tubular system. AB - Exfoliated human urinary tract epithelial cells and renal tubular cells from urinary sediments of healthy adults, of urological patients and of internal patients were isolated and cultured. Cells started proliferating within 1 week after seeding a sediment. Proliferating cells formed colonies of different morphologies, designated as type-1 or type-2 cell colonies. Type-1 cell colonies showed irregular contours and spindle-like cells within the colonies. Subcultivation of type-1 cells for up to six passages was possible. Type-2 cell colonies showed smooth-edged contours and subcultivation was not possible. The epithelial character of type-1 cells was demonstrated by positive immunohistochemical staining for cytokeratin-7. In contrast to carbonic anhydrase positive stained Madin Darby canine kidney cells (MDCK), which were used as positive controls for renal tubular cells, type-1 cells were carbonic anhydrase negative on staining with the cobalt phosphate method. This indicates that type-1 cells were not of renal tubular origin. Type-2 cells were positively stained for carbonic anhydrase, indicating that type-2 cells were renal tubular cells. Type-2 cell colonies could be assigned to two subgroups with different cell forms. Colonies of cobblestone-like cells more often occurred than type-2 cell colonies with spindle-like cells, which are described in this study for the first time. Colonies with cobblestone-like cells formed domes (hemicysts), whereas spindle like type-2 cell colonies did not. Cultures of urinary sediments from healthy adults, elderly multimorbid patients treated with furosemide, and urological patients with urolithiasis treated with sulfamethoxazole/trimethoprim and/or with a percutaneous nephrostomy catheter were compared. In 52% of all cultured sediments from healthy adults, in 30% of those from multimorbid patients, and in 75-80% of those from urological patients cells proliferated to colonies. The ratios of type-1 to type-2 cell colonies were 3.3:1 (healthy adults), 1.4:1 (urological patients with urolithiasis), and 1.8:1 (urological patients with urolithiasis, urine was directly collected from the renal pelvis with a percutaneous nephrostomy catheter). Successful cultures of the urinary sediments from these three groups revealed means of 3 or 4 colonies, 14 colonies, and 21 colonies, respectively. Differences in the number of colonies in relation to sex were observed only for the group of urological patients. It was shown that type-1 cells were urothelial cells, which did not show morphological differences due to their locations of origin within the urinary tract, whereas type-2 cells were probably renal tubular cells. These findings offer new aspects in the culturing of human urothelial or kidney epithelial cells with a method based on noninvasive collecting of specimens and requiring only minimal culture effort. The cultures obtained by this method can be used for in vitro studies in toxicological and clinical research. PMID- 11201670 TI - Sweat gland toxicity induced by bis (tributyltin) oxide: an ultrastructural and X ray microanalysis study. AB - Acute toxicity of bis (tributyltin) oxide in the sweat glands in the rat footpad was investigated by electron microscopy and an energy-dispersive X-ray microanalyzer. Male Wistar rats received an intramuscular injection of 0.5 ml/kg bis (tributyltin) oxide. After 6-8 h, swelling of mitochondria appeared in the secretory cells of the sweat glands. After 12 h, the secretory cells began to show intracytoplasmic edema. After 16-20 h, secretory cells in some sweat glands showed marked hydropic degeneration with swollen cytoplasm. Using X-ray microanalysis, tin peaks were preferentially obtained from the swollen mitochondria of the affected secretory cells. Mitochondria dysfunction due to the toxic effects of bis (tributyltin) oxide induced changes in the secretory cells of rat sweat glands. After 24-48 h, the secretory portion of the sweat glands contained three types of cells: degenerating dark cells, regenerating cells carrying injured mitochondria, and light cells which were morphologically very similar to the cells in the transitional portion of the sweat gland. These light cells appeared to differentiate into active secretory cells after settling down in the secretory portion. Based on these observations, we concluded that the cells in the transitional portion could play an important role at least as reserve cells against secretory cell toxicity. In association with the regenerating process of the damaged secretory portions, increased mitotic activities were seen in different areas of all the dermal sweat ducts. The above mentioned morphological observations for cell damage and subsequent regeneration and renewal ofsecretory cells in sweat gland intoxication have not been reported so far. PMID- 11201671 TI - Suppression of decidual cell response induced by tributyltin chloride in pseudopregnant rats: a cause of early embryonic loss. AB - In our previous studies, tributyltin chloride (TBTCl) at doses of 16.3 mg/kg and above caused implantation failure (preimplantation embryonic loss) and postimplantation embryonic loss in rats following administration on gestational day (GD) 0 through GD 3 and GD 4 through GD 7, respectively. This study was designed to assess the effects of TBTCl on uterine function as a cause of early embryonic loss in pseudopregnant rats. TBTCl was given orally to pseudopregnant rats at doses of 4.1, 8.1, 16.3 and 32.5 mg/kg on pseudopregnant day (PPD) 0 to PPD 3 or 8.1, 16.3, 32.5 and 65.1 mg/kg on PPD 4 to PPD 7. The decidual cell response was induced by bilateral scratch trauma on PPD 4. The uterine weight on PPD 9 served as an index of uterine decidualization. Uterine weight and serum progesterone levels on PPD 9 were significantly decreased after administration of TBTCl at doses of 16.3 mg/kg and above on PPD 0 to PPD 3 or PPD 4 to PPD 7. Administration of TBTCl at doses of 8.1 mg/kg and above on PPD 0 to 3 also significantly decreased serum progesterone levels on PPD 4. TBTCl had no effect on ovarian weight and number of corpora lutea. It can be concluded that TBTCl suppresses the uterine decidual cell response and decreases progesterone levels, and these effects are responsible for early embryonic loss due to TBTCl exposure. PMID- 11201672 TI - Mutagenicity of N-nitrosodiethylamine in the Ames test with S. typhimurium TA1535 is due to volatile metabolites and is not dependent on cytochrome P4502E1 induction. AB - N-Nitrosodiethylamine (NDEA) is carcinogenic in all investigated animal species at relatively low dosages. No threshold has been detected for these carcinogenic effects. The substance has been extensively investigated in various in vitro systems, revealing only weak mutagenicity at relatively high dosages. We reinvestigated NDEA in the Ames test with Salmonella typhimurium TA1535 to establish appropriate modifications of the standard Ames test protocol, to achieve a dose-dependent mutagenic response at a reasonably low dose range. Two main modifications were evaluated. Since the metabolism of dialkylnitrosamines is postulated to be mainly dependent on cytochrome P4502E1, a pyrazole-induced rat liver S9 was applied. The second modification involved a gastight preincubation, since metabolites of NDEA might evaporate from the incubation mixture. Cytochrome P4502E1 induction in Wistar rats was achieved by pyrazole treatment. For comparison, a rat liver S9-fraction produced by beta-naphtoflavone/phenobarbital induction was used. N-Nitrosopyrrolidine served as positive control for pyrazole induced S9-mix with TA1535. NDEA showed no mutagenic response under all test conditions in the presence of pyrazole-induced S9-mix. A strong mutagenic response, exceeding the base rate up to 15-fold at a dose range of 25-1000 microg/plate, was observed using beta-naphtoflavone/phenobarbital-induced S9-mix, gastight preincubation and TA1535. In conclusion the Ames test with gastight preincubation can be useful for the testing of volatile compounds or substances leading to gaseous metabolites. The weak response of NDEA in the Ames test observed previously seems mainly to be due to the volatile character of its mutagenic metabolites. Our results do not support the hypothesis that cytochrome P4502E1 is a major toxifying enzyme for the formation of Ames-test-positive metabolites from NDEA. PMID- 11201673 TI - An approach to cancer risk assessment for the food constituent 2-hexenal on the basis of 1,N2-propanodeoxyguanosine adducts of 2-hexenal in vivo. AB - 2-Hexenal is formed by plants, and humans are regularly exposed to this mutagenic/genotoxic compound via vegetable foods. 2-Hexenal has not been tested for carcinogenicity, but it forms exocyclic 1,N2-propanodeoxyguanosine adducts like other carcinogenic alpha,beta-unsaturated carbonyl compounds. To quantify the respective DNA adducts as an approach to a theoretical cancer risk assessment, we used a newly developed 32P-postlabelling technique based on nuclease P1 enrichment, allowing a detection limit of 3 adducts per 10(8) nucleotides. Adduct levels were measured at different doses and the covalent binding index (CBI) was found to be dose-dependent. This can be explained by glutathione depletion at higher doses. The CBI at low doses was 0.06. A negligible cancer risk of 1-5 per 10(7) lives was estimated on the basis of TD50 values calculated from the correlation between CBI and TD50 of Lutz and on the daily intake of 2-hexenal via vegetable foods, fruit juices and black tea. A risk of 1.6-8.5 per 10(6) lives was estimated for the hypothetical case of glutathione depletion, e.g. due to consuming special medicaments. In every case, the benefit from eating fruit and vegetables is clearly higher than a possible low and unavoidable cancer risk. Utilization of 2-hexenal as a flavouring agent or as a fungicide, breeding fungus-resistant plants or technological gene construction of fungus resistance may lead to a high hypothetical cancer risk of 2-6 per 10(4) lives under certain circumstances which are avoidable and deserves special case by-case consideration. PMID- 11201674 TI - Tobacco and cancer. PMID- 11201675 TI - The rise and fall of prostate cancer. PMID- 11201676 TI - Assessments of physical activity and cancer risk. AB - The assessment of physical activity is one of the most important methodological issues in research into physical activity and cancer risk. A sedentary Western lifestyle has been observed to influence biological mechanisms promoting development of certain types of cancer. At present the totality of evidence supports a protective effect against cancers of the colon and probably the breast, while further data concerning carcinoma of other cancers are required. Thus, physical activity represents a powerful public health measure for reducing cancer risk. Studies of the association between physical activity and cancer risk have used a great variety of methods, but have most often included work and/or leisure time activity. Questionnaires are the method most often used and various components of physical activity such as type, frequency, intensity and lifetime physical activity have been recorded. However, the measurements used when assessing physical activity have been hampered by lack of accuracy as regards validity and reliability, missing information on the various components of physical activity and sparse information of lifetime exposure, and often no repeat assessments in cohort studies. Discrepancies between studies elaborating the association between physical activity and site-specific cancer risk may be explained through real differences or lack of information on the various components of physical activity (type, intensity, duration) and incomplete information about the cancer type studied (localization, histological type). The complicated nature of the variable physical activity, combined with incomplete understanding of the pathogenesis of most cancer and lack of knowledge regarding possible biological mechanisms operating between physical activity and cancer, warrants further studies. In these studies methodological improvements in measuring physical activity, combined with inclusion of physiological markers (heart rate, energy balance, hormonal levels, etc.) reflecting the variety of physical activities performed are of particular interest. Assessing biomarkers and intermediate steps for site-specific cancer risk may give us further insight into the relation between physical activity and cancer that will be of enormous interest for public health recommendations. PMID- 11201678 TI - Stomach cancer history in the siblings of patients with gastric carcinoma. AB - A case-control study in the population of the Eastern Black Sea region of Turkey was conducted to learn the incidence of stomach cancer in the siblings of patients with gastric carcinoma. Among 1240 patients with gastric carcinoma, 168 had sibling(s) with a history of stomach cancer versus 19 cases in the control group matched according to age and gender (OR 10.07, P < 0.0001). The frequency of a history of stomach cancers and cancer of other organs in first- to third degree relatives was 60.7% and 38.0%, respectively, of 168 sibling cases with gastric carcinoma (P < 0.0001). Fifty-two point three per cent of sibling cases having a history of cancer in other organs in their relatives also reported stomach cancer in the same-degree relatives. The number of stomach cancers in the first- to third-degree relatives of sibling cases was higher than the number of other organ cancers in the same-degree relatives (P < 0.01). Familial clustering of stomach cancer was reported in 12.5% of sibling cases. The study of stomach cancer history in the siblings suggests: the presence of a genetic susceptibility, high risk of the disease occurrence in the siblings of patients, higher predisposition to gastric than to other organ cancers in the relatives, and not infrequent familial clustering. PMID- 11201677 TI - Diet and lung cancer: a new approach. AB - Lung cancer is one of major public health problems facing the world today, owing to the high incidence of the disease and its poor prognosis. Although the principal cause of lung cancer is tobacco use, smokers find it extremely difficult to quit the habit. Hence, there is a need to take action targeted at other risk factors for this disease. One such factor is diet, which is known to be able to raise or lower the risk of lung cancer. This paper seeks to complement other reviews in the field and to shed more light both on the influence that dietary factors may have upon the occurrence of this neoplasm and on the causes of this possible effect. PMID- 11201679 TI - Migration, socio-economic status and the risk of colorectal cancer in Italy. AB - To assess how the risk of cancer of the colon and rectum relates to place of birth and socio-economic status, we analysed data from an Italian case-control study. Data included 1225 cases with a recent diagnosis of cancer of the colon (ages 19-74 years), 728 cases of cancer of the rectum (ages 23-74 years) and 4154 controls (ages 19-74 years), frequency-matched with cases by age and catchment area and admitted to hospitals for a wide spectrum of acute non-neoplastic conditions. Compared with residents born in the north of Italy, migrants from the centre and south had an odds ratio (OR) of 0.7 (95% CI 0.5-0.9) for colon cancer and OR of 0.9 (95% CI 0.7-1.2) for cancer of the rectum. The inverse association of migration with colon cancer was stronger among women (OR 0.5, 95% CI 0.4-0.8) than among men (OR 0.8, 95% CI 0.6-1.1), and was independent of education and occupation. Among migrants, the direct association between education and colon cancer risk was less clear than among non-migrants. In conclusion, place of origin played an independent role in colon cancer aetiology. Results on rectal cancer were less clear, although in the same direction. Among migrants, those less susceptible to behavioural changes (e.g. women) retained most of the benefit associated with their place of origin. PMID- 11201680 TI - Biliary lipid peroxidation products in gallbladder cancer: increased peroxidation or biliary stasis? AB - Gallbladder cancer is a common malignancy among women in India. The aetiology of gallbladder carcinoma is still obscure and although numerous factors have been implicated, none has stood the test of time. This study was carried out to evaluate the role of lipid peroxidation product 4-hydroxynonenal (HNE) in gallbladder carcinogenesis. High-performance liquid chromatography (HPLC) analysis was carried out in 30 bile samples obtained during laparotomy from patients with gallbladder cancer (n = 10), cholelithiasis (n = 10) and age- and sex-matched controls (n = 10). A significantly high concentration of HNE and lower concentration of biliary pH and electrolyte was observed in patients with carcinoma of the gallbladder compared with controls and patients with cholelithiasis. A significant correlation was also observed between biliary Na+ and K+ (r = 0.72), biliary Ca2+ and Na+ (r = 0.69) among controls. However, there was no correlation between HNE, electrolytes and pH among cancer patients. An increased concentration of biliary HNE and decreased concentration of electrolytes suggest biliary stasis rather then increased peroxidation in cancer patients. PMID- 11201681 TI - Tobacco smoking and vitamin C concentration in gastric juice in healthy subjects and patients with Helicobacter pylori infection. AB - Low gastric juice total vitamin C concentration in the presence of Helicobacter pylori infection probably plays a role in gastric carcinogenesis. Vitamin C plays a role in the neutralization of various pathogenic factors connected with H. pylori infection, including the destruction of free radicals, which damage tissues and cell DNA, and inhibition of the formation of N-nitroso compounds, which have a strong carcinogenic activity. The aim of the study was to determine whether tobacco smoking had any effect on gastric juice vitamin C concentration in healthy subjects and in patients infected with H. pylori. Eighty-six patients with dyspeptic symptoms undergoing routine endoscopy entered the study after giving informed consent. In all patients plasma and gastric juice total vitamin C levels were measured by a spectrophotometric method. They were entered into four groups: group I (controls) - H. pylori-negative non-smokers (n = 17), group II - H. pylori-negative smokers (n = 16), group III - non-smokers with H. pylori infection (n = 21), and group IV - H. pylori-infected smokers (n = 32). In the control group (I) the mean gastric juice total vitamin C concentration was 17.1 microg/ml (range 5.3-40.0 microg/ml), which was significantly higher (P < 0.05) than in group II (12.6 microg/ml, range 5.1-21.0 microg/ml), group III (5.8 microg/ml range 2.1-13.7 microg/ml) and group IV (3.9 microg/ml, range 1.1-10.6 microg/ml) (P < 0.001). Statistically significant differences also were noted between groups II and III (P < 0.01) and groups II and IV (P < 0.001) and between groups III and IV (P < 0.05). These results demonstrate that the concentration of vitamin C in gastric juice is significantly lower in smokers than in non-smokers. This was observed in healthy subjects as well as H. pylori-infected patients. This phenomenon may be one of the mechanisms whereby smoking contributes to the production of gastric lesions, impairs healing of peptic ulcers and also increases the recurrence rate of peptic ulcers in cases with H. pylori infection. PMID- 11201682 TI - Allelic polymorphism of GSTM1 and NAT2 genes modifies dietary-induced DNA damage in colorectal mucosa. AB - Typically, cancer is caused by the interaction of genetic and environmental factors. In colorectal carcinogenesis, diet and nutritional habits are the most important external risk determinants. Allelic polymorphisms of certain metabolizing enzymes may have an influence on cancer risk by modifying the concentration of active carcinogenic compounds in the body. In the present study we investigated the interaction between nutritional and genetic susceptibility factors in human colon carcinogenesis. Healthy volunteers were divided into four groups, based on allelic polymorphisms of N-acetyltransferase 2 and glutathione-S transferase M1 enzymes. Comet assay was used to determine the level of DNA strand breaks in exfoliated colorectal mucosal cells, following a 2-day vegetarian diet, and after switching to a 2-day 'high-meat' diet. The 'high-meat' diet statistically significantly increased the amount of single-strand breaks in rapid acetylators and among individuals with a GSMT1 + genotype, while it caused only a slight and not significant increase in the other groups. Our study emphasizes the importance of using susceptibility markers in cancer epidemiology, since environmental effects are strongly modified by these genetic factors. PMID- 11201683 TI - Tonsillar and other upper aerodigestive tract cancers among cervical cancer patients and their husbands. AB - The study aimed at probing the possible role of human papillomavirus (HPV) infection in squamous cell carcinomas of the upper aerodigestive tract, with a special reference to tonsillar cancer. We used the Swedish Family Cancer Database to analyse second cancers in the upper aerodigestive tract of women first diagnosed with in-situ or invasive cervical cancer. First cancers of their husbands were also analysed. Standardized incidence ratios (SIRs) were calculated for female and male cancers, adjusted for age at diagnosis, period, sex, socio economic status and residential area. Among women, increases were observed at many sites, but tonsillar cancers were increased only among women aged 50 years or more at diagnosis of in-situ cervical cancer (SIR 2.58). The increases at these sites are probably ascribed to the effects HPV, smoking, alcohol or their interaction. Husbands of cervical cancer patients developed an excess (SIR over 2.00) of both tonsillar cancer (SIR 2.39 when wife with in-situ cancer and SIR 2.72 when wife with invasive cervical cancer) and cancer of the tongue. The excess of tonsillar cancer among husbands of women with HPV-associated neoplastic lesions of the cervix supports the a priori hypothesis that HPV may be involved in tonsillar carcinogenesis. PMID- 11201684 TI - Comparison of early onco/suppressor gene expressions in peripheral leukocytes and potential target organs of rats exposed to the carcinogen 1-nitropyrene. AB - An in-vivo model has been developed to study early expressions of c-myc, Ha-ras oncogenes and p53 suppressor gene as biomarkers of carcinogenic exposure and/or tumorigenesis. In order to validate the in-vivo expression changes as biomarkers, rats were treated with the outdoor air pollutant carcinogen 1-nitropyrene. The gene expression levels were measured after 24 and 48 h in potential target tissues (lung, liver, lymph nodes, kidneys, spleen) and in peripheral blood leukocytes. Another main objective was to prove the applicability of leukocytes as a surrogate tissue, having a similar expression pattern of the selected genes upon carcinogenic exposure. The c-myc oncogene was not suitable as an early biomarker because of the lack or low level of its expression. However, in the case of the other oncogene Ha-ras and the suppressor gene p53, remarkable and early changes were detected in the expression signals. Similar expression patterns could only be detected in leukocytes and the spleen; therefore we continue this validation study by using other types and routes of exposure. PMID- 11201685 TI - Meat and nutrition, Hamburg: 17-18 October 2000. PMID- 11201686 TI - Our role as family physicians in vaccine safety. PMID- 11201687 TI - Increasing the success of antihypertensive therapy. PMID- 11201689 TI - A plan for patients who wish to quit smoking. PMID- 11201688 TI - Behavioral medicine in patients with MVP. PMID- 11201690 TI - Diagnostic curettage in the evaluation of ectopic pregnancy. PMID- 11201691 TI - Smoking and age-related macular degeneration. PMID- 11201692 TI - Common infections in older adults. AB - Infectious diseases account for one third of all deaths in people 65 years and older. Early detection is more difficult in the elderly because the typical signs and symptoms, such as fever and leukocytosis, are frequently absent. A change in mental status or decline in function may be the only presenting problem in an older patient with an infection. An estimated 90 percent of deaths resulting from pneumonia occur in people 65 years and older. Mortality resulting from influenza also occurs primarily in the elderly. Urinary tract infections are the most common cause of bacteremia in older adults. Asymptomatic bacteriuria occurs frequently in the elderly; however, antibiotic treatment does not appear to be efficacious. The recent rise of antibiotic-resistant bacteria (e.g., methicillin resistant Staphylococcus aureus and vancomycin-resistant enterococcus) is a particular problem in the elderly because they are exposed to infections at higher rates in hospital and institutional settings. Treatment of colonization and active infection is problematic; strict adherence to hygiene practices is necessary to prevent the spread of resistant organisms. PMID- 11201693 TI - Sleep disorders and sleep problems in childhood. AB - Sleep problems are common in childhood. A distinction is made between problems in which polysomnography is abnormal (i.e., the parasomnias, sleep apnea and narcolepsy) and problems that are behavioral in origin and have normal polysomnography. The parasomnias--sleep terrors, somnambulism and enuresis- appear to be related to central nervous system immaturity and are often outgrown. Obstructive sleep apnea syndrome (OSAS) is frequently missed in children and can often be cured through surgery. Behavioral sleep problems may be overcome after parents make interventions. Physicians can be of great assistance to these families by recommending techniques to parents that have been shown to be effective. PMID- 11201694 TI - Evaluation of incidental renal and adrenal masses. AB - Incidental renal or adrenal masses are sometimes found during imaging for problems unrelated to the kidneys and adrenal glands. Knowledgeable family physicians can reliably diagnose these masses, thereby avoiding unnecessary worry and procedures for their patients. A practical and cost-efficient means of evaluating renal lesions combines ultrasonography and computed tomographic scanning, with close communication between the family physician and the radiologist. Asymptomatic patients with simple renal cysts require no further evaluation. Patients with minimally complicated renal cysts can be followed radiographically. Magnetic resonance imaging is indicated in patients with indeterminate renal masses, and referral is required in patients with symptoms or solid masses. The need for referral of patients with adrenal masses is determined by careful assessment of clinical signs and symptoms, as well as the results of screening laboratory studies and appropriate radiologic studies. Referral is indicated for patients with incidental adrenal masses more than 6 cm in greatest diameter. Appropriate laboratory screening tests include the following: a 24-hour urinary free cortisol measurement for patients with evidence of Cushing's syndrome; a 24-hour urinary metanephrine, vanillylmandelic acid or catecholamine measurement for patients with evidence of pheochromocytoma; and a serum potassium level for patients with evidence of hyperaldosteronism. PMID- 11201695 TI - Management of suspected fetal macrosomia. AB - Fetal macrosomia, arbitrarily defined as a birth weight of more than 4,000 g (8 lb, 13 oz) complicates more than 10 percent of all pregnancies in the United States. It is associated with increased risks of cesarean section and trauma to the birth canal and the fetus. Fetal macrosomia is difficult to predict, and clinical and ultrasonographic estimates of fetal weight are prone to error. Elective cesarean section for suspected macrosomia results in a high number of unnecessary procedures, and early induction of labor to limit fetal growth may result in a substantial increase in the cesarean section rate because of failed inductions. Pregnancies complicated by fetal macrosomia are best managed expectantly. When labor fails to progress as expected, the possibility of fetopelvic disproportion should be considered within the context of the best estimate of the fetal weight. PMID- 11201696 TI - Effective use of statins to prevent coronary heart disease. AB - Primary and secondary prevention trials have shown that use of 3-hydroxy-3 methylglutaryl coenzyme A reductase inhibitors (also known as statins) to lower an elevated low-density lipoprotein cholesterol level can substantially reduce coronary events and death from coronary heart disease. In 1987 and 1993, the National Cholesterol Education Program promulgated guidelines for cholesterol screening and treatment. Thus far, however, primary care physicians have inadequately adopted these guidelines in clinical practice. A 1991 study found that cholesterol screening was performed in only 23 percent of patients. Consequently, many patients with elevated low-density lipoprotein levels and a high risk of primary or recurrent ischemic events remain unidentified and untreated. A study published in 1998 found that fewer than 15 percent of patients with known coronary heart disease have low-density lipoprotein levels at the recommended level of below 100 mg per dL (2.60 mmol per L). By identifying patients with elevated low-density lipoprotein levels and instituting appropriate lipid-lowering therapy, family physicians could help prevent cardiovascular events and death in many of their patients. PMID- 11201697 TI - Sporotrichoid lymphocutaneous infections: etiology, diagnosis and therapy. AB - Sporotrichoid lymphocutaneous infection is an uncommon syndrome that is often misdiagnosed and improperly treated. Of the several hundred cases seen each year in the United States, the majority are caused by Sporothrix schenckii, Nocardia brasiliensis, Mycobacterium marinum or Leishmania brasiliensis. The "sporotrichoid" disease begins at a site of distal inoculation and leads to the development of nodular lymphangitis. Systemic symptoms are characteristically absent. By recognizing the distinct pattern of nodular lymphangitis and focusing on the diverse but limited etiologies, the physician can obtain the appropriate histologic and microbiologic studies and start targeted antimicrobial therapy. Therapy is generally continued for two to three months after the resolution of cutaneous disease. PMID- 11201698 TI - ACIP issues updated recommendations for polio vaccine. Advisory Committee on Immunization Practices. PMID- 11201700 TI - Deep waters. PMID- 11201701 TI - Don't underestimate the enemy. PMID- 11201702 TI - The stuff of ideas. PMID- 11201703 TI - Harvard to spend 'hundreds of millions' on further expansion. PMID- 11201704 TI - Biotech sector still looking lively. PMID- 11201705 TI - Japanese legume project may help to fix nitrogen problem. PMID- 11201706 TI - South Africa reveals funding allocations for research. PMID- 11201707 TI - Group urges survey of antibiotics in animals. PMID- 11201708 TI - French museum report sparks researchers' revolt. PMID- 11201709 TI - Genes may solve hormone-disrupter debate. PMID- 11201710 TI - Spanish leader lends ear to science. PMID- 11201711 TI - CNN founder launches arms control initiative. PMID- 11201712 TI - BSE fallout sends shock waves through Germany. PMID- 11201713 TI - Polio's last stand. PMID- 11201714 TI - Funding assured for India's international biotechnology centre... PMID- 11201715 TI - And senior staff say there's no problem. PMID- 11201716 TI - Doing our best for returners to Spain. PMID- 11201717 TI - Difficulty in reconciling global-warming data. PMID- 11201718 TI - The birth of scientific reading. PMID- 11201719 TI - The key to the past? PMID- 11201720 TI - Wireless communications. Talk is cheap in the city. PMID- 11201722 TI - Geochemistry. New prospects for old gas. PMID- 11201721 TI - Diabetes. The missing link with obesity? PMID- 11201724 TI - Pulsars crash the magnetar party. PMID- 11201725 TI - Evolution. Speciation in the round. PMID- 11201726 TI - Cats, dogs and categories. PMID- 11201723 TI - RNA silencing. Diced defence. PMID- 11201727 TI - Water structure. Order and oddities. PMID- 11201728 TI - A viable herd of genetically uniform cattle. PMID- 11201729 TI - Topology of two-dimensional C60 domains. PMID- 11201730 TI - Self-recognition and the right hemisphere. PMID- 11201731 TI - Life, geology and snowball Earth. PMID- 11201733 TI - Non-detection at Venus of high-frequency radio signals characteristic of terrestrial lightning. AB - The detection of impulsive low-frequency (10 to 80 kHz) radio signals, and separate very-low-frequency (approximately 100 Hz) radio 'whistler' signals provided the first evidence for lightning in the atmosphere of Venus. Later, a small number of impulsive high-frequency (100 kHz to 5.6 MHz) radio signals, possibly due to lightning, were also detected. The existence of lightning at Venus has, however, remained controversial. Here we report the results of a search for high-frequency (0.125 to 16 MHz) radio signals during two close fly bys of Venus by the Cassini spacecraft. Such signals are characteristic of terrestrial lightning, and are commonly heard on AM (amplitude-modulated) radios during thunderstorms. Although the instrument easily detected signals from terrestrial lightning during a later fly-by of Earth (at a global flash rate estimated to be 70 s(-1), which is consistent with the rate expected for terrestrial lightning), no similar signals were detected from Venus. If lightning exists in the venusian atmosphere, it is either extremely rare, or very different from terrestrial lightning. PMID- 11201732 TI - The hormone resistin links obesity to diabetes. AB - Diabetes mellitus is a chronic disease that leads to complications including heart disease, stroke, kidney failure, blindness and nerve damage. Type 2 diabetes, characterized by target-tissue resistance to insulin, is epidemic in industrialized societies and is strongly associated with obesity; however, the mechanism by which increased adiposity causes insulin resistance is unclear. Here we show that adipocytes secrete a unique signalling molecule, which we have named resistin (for resistance to insulin). Circulating resistin levels are decreased by the anti-diabetic drug rosiglitazone, and increased in diet-induced and genetic forms of obesity. Administration of anti-resistin antibody improves blood sugar and insulin action in mice with diet-induced obesity. Moreover, treatment of normal mice with recombinant resistin impairs glucose tolerance and insulin action. Insulin-stimulated glucose uptake by adipocytes is enhanced by neutralization of resistin and is reduced by resistin treatment. Resistin is thus a hormone that potentially links obesity to diabetes. PMID- 11201734 TI - Tripling the capacity of wireless communications using electromagnetic polarization. AB - Wireless communications are a fundamental part of modern information infrastructure. But wireless bandwidth is costly, prompting a close examination of the data channels available using electromagnetic waves. Classically, radio communications have relied on one channel per frequency, although it is well understood that the two polarization states of planar waves allow two distinct information channels; techniques such as 'polarization diversity' already take advantage of this. Recent work has shown that environments with scattering, such as urban areas or indoors, also possess independent spatial channels that can be used to enhance capacity greatly. In either case, the relevant signal processing techniques come under the heading of 'multiple-input/multiple-output' communications, because multiple antennae are required to access the polarization or spatial channels. Here we show that, in a scattering environment, an extra factor of three in channel capacity can be obtained, relative to the conventional limit using dual-polarized radio signals. The extra capacity arises because there are six distinguishable electric and magnetic states of polarization at a given point, rather than two as is usually assumed. PMID- 11201735 TI - Relationship between structural order and the anomalies of liquid water. AB - In contrast to crystalline solids--for which a precise framework exists for describing structure--quantifying structural order in liquids and glasses has proved more difficult because even though such systems possess short-range order, they lack long-range crystalline order. Some progress has been made using model systems of hard spheres, but it remains difficult to describe accurately liquids such as water, where directional attractions (hydrogen bonds) combine with short range repulsions to determine the relative orientation of neighbouring molecules as well as their instantaneous separation. This difficulty is particularly relevant when discussing the anomalous kinetic and thermodynamic properties of water, which have long been interpreted qualitatively in terms of underlying structural causes. Here we attempt to gain a quantitative understanding of these structure-property relationships through the study of translational and orientational order in a models of water. Using molecular dynamics simulations, we identify a structurally anomalous region--bounded by loci of maximum orientational order (at low densities) and minimum translational order (at high densities)--in which order decreases on compression, and where orientational and translational order are strongly coupled. This region encloses the entire range of temperatures and densities for which the anomalous diffusivity and thermal expansion coefficient of water are observed, and enables us to quantify the degree of structural order needed for these anomalies to occur. We also find that these structural, kinetic and thermodynamic anomalies constitute a cascade: they occur consecutively as the degree of order is increased. PMID- 11201736 TI - Transparent nematic phase in a liquid-crystal-based microemulsion. AB - Complex fluids are usually produced by mixing together several distinct components, the interactions between which can give rise to unusual optical and rheological properties of the system as a whole. For example, the properties of microemulsions (composed of water, oil and surfactants) are determined by the microscopic structural organization of the fluid that occurs owing to phase separation of the component elements. Here we investigate the effect of introducing an additional organizing factor into such a fluid system, by replacing the oil component of a conventional water-in-oil microemulsion with an intrinsically anisotropic fluid--a nematic liquid crystal. As with the conventional case, the fluid phase-separates into an emulsion of water microdroplets (stabilized by the surfactant as inverse micelles) dispersed in the 'oil' phase. But the properties are further influenced by a significant directional coupling between the liquid-crystal molecules and the surfactant tails that emerge (essentially radially) from the micelles. The result is a modified bulk-liquid crystal that is an ordered nematic at the mesoscopic level, but which does not exhibit the strong light scattering generally associated with bulk nematic order: the bulk material here is essentially isotropic and thus transparent. PMID- 11201737 TI - Increased thermohaline stratification as a possible cause for an ocean anoxic event in the Cretaceous period. AB - Ocean anoxic events were periods of high carbon burial that led to drawdown of atmospheric carbon dioxide, lowering of bottom-water oxygen concentrations and, in many cases, significant biological extinction. Most ocean anoxic events are thought to be caused by high productivity and export of carbon from surface waters which is then preserved in organic-rich sediments, known as black shales. But the factors that triggered some of these events remain uncertain. Here we present stable isotope data from a mid-Cretaceous ocean anoxic event that occurred 112 Myr ago, and that point to increased thermohaline stratification as the probable cause. Ocean anoxic event 1b is associated with an increase in surface-water temperatures and runoff that led to decreased bottom-water formation and elevated carbon burial in the restricted basins of the western Tethys and North Atlantic. This event is in many ways similar to that which led to the more recent Plio-Pleistocene Mediterranean sapropels, but the greater geographical extent and longer duration (approximately 46 kyr) of ocean anoxic event 1b suggest that processes leading to such ocean anoxic events in the North Atlantic and western Tethys were able to act over a much larger region, and sequester far more carbon, than any of the Quaternary sapropels. PMID- 11201738 TI - 300-Myr-old magmatic CO2 in natural gas reservoirs of the west Texas Permian basin. AB - Except in regions of recent crustal extension, the dominant origin of carbon dioxide in fluids in sedimentary basins has been assumed to be from crustal organic matter or mineral reactions. Here we show, by contrast, that Rayleigh fractionation caused by partial degassing of a magma body can explain the CO2/3He ratios and delta13C(CO2) values observed in CO2-rich natural gases in the west Texas Val Verde basin and also the mantle 3He/22Ne ratios observed in other basin systems. Regional changes in CO2/3He and CO2/CH4 ratios can be explained if the CO2 input pre-dates methane generation in the basin, which occurred about 280 Myr ago. Uplift to the north of the Val Verde basin between 310 and 280 Myr ago appears to be the only tectonic event with appropriate timing and location to be the source of the magmatic CO2. Our identification of magmatic CO2 in a foreland basin indicates that the origin of CO2 in other mid-continent basin systems should be re-evaluated. Also, the inferred closed-system preservation of natural gas in a trapping structure for approximately 300 Myr is far longer than the residence time predicted by diffusion models. PMID- 11201739 TI - The electric Moho. AB - Since Mohorovicic discovered a dramatic increase in compressional seismic velocity at a depth of 54 km beneath the Kulpa Valley in Croatia, the 'Moho' has become arguably the most important seismological horizon in Earth owing to its role in defining the crust-mantle boundary. It is now known to be a ubiquitous feature of the Earth, being found beneath both the continents and the oceans, and is commonly assumed to separate lower-crustal mafic rocks from upper-mantle ultramafic rocks. Electromagnetic experiments conducted to date, however, have failed to detect a corresponding change in electrical conductivity at the base of the crust, although one might be expected on the basis of laboratory measurements. Here we report electromagnetic data from the Slave craton, northern Canada, which show a step-change in conductivity at Moho depths. Such resolution is possible because the Slave craton is highly anomalous, exhibiting a total crustal conductance of less than 1 Siemens--more than an order of magnitude smaller than other Archaean cratons. We also found that the conductivity of the uppermost continental mantle directly beneath the Moho is two orders of magnitude more conducting than laboratory studies on olivine would suggest, inferring that there must be a connected conducting phase. PMID- 11201740 TI - Speciation in a ring. AB - The evolutionary divergence of a single species into two has never been directly observed in nature, primarily because speciation can take a long time to occur. A ring species, in which a chain of intergrading populations encircles a barrier and the terminal forms coexist without interbreeding, provides a situation in which variation in space can be used to infer variation in time. Here we reconstruct the pathway to speciation between two reproductively isolated forms of greenish warbler (Phylloscopus trochiloides). These two taxa do not interbreed in central Siberia but are connected by a long chain of intergrading populations encircling the Tibetan Plateau to the south. Molecular data and climatic history imply that the reproductively isolated taxa came into contact following expansions northward around the western and eastern sides of the plateau. Parallel selection pressures for increased song complexity during the northward expansions have been accompanied by divergence in song structure. Playback experiments show that the two Siberian forms do not recognize each other's songs. Our results show how gradual divergence in a trait involved in mate choice leads to the formation of new species. PMID- 11201741 TI - Three-butterfly system provides a field test of mullerian mimicry. AB - In 1879, Muller proposed that two brightly coloured distasteful butterfly species (co-models) that share a single warning-colour pattern would benefit by spreading the selective burden of educating predators. The mutual benefit of sharing warning signals among distasteful species, so-called mullerian mimicry, is supported by comparative evidence, theoretical studies and laboratory simulations; however, to date, this key exemplar of adaptive evolution has not been experimentally tested in the field. To measure natural selection generated by mullerian mimicry, I exploited the unusual polymorphism of Heliconius cydno (Lepidoptera: Nymphalidae). Here I show increased survival of H. cydno morphs that match locally abundant monomorphic co-model species. This study demonstrates mullerian mimicry in the field. It also shows that mullerian mimicry with several co-models generates geographically divergent selection, which explains the existence of polymorphism in distasteful species with warning coloration. PMID- 11201742 TI - Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration. AB - Nogo has been identified as a component of the central nervous system (CNS) myelin that prevents axonal regeneration in the adult vertebrate CNS. Analysis of Nogo-A has shown that an axon-inhibiting domain of 66 amino acids is expressed at the extracellular surface and at the endoplasmic reticulum lumen of transfected cells and oligodendrocytes. The acidic amino terminus of Nogo-A is detected at the cytosolic face of cellular membranes and may contribute to inhibition of axon regeneration at sites of oligodendrocyte injury. Here we show that the extracellular domain of Nogo (Nogo-66) inhibits axonal extension, but does not alter non-neuronal cell morphology. In contrast, a multivalent form of the N terminus of Nogo-A affects the morphology of both neurons and other cell types. Here we identify a brain-specific, leucine-rich-repeat protein with high affinity for soluble Nogo-66. Cleavage of the Nogo-66 receptor and other glycophosphatidylinositol-linked proteins from axonal surfaces renders neurons insensitive to Nogo-66. Nogo-66 receptor expression is sufficient to impart Nogo 66 axonal inhibition to unresponsive neurons. Disruption of the interaction between Nogo-66 and its receptor provides the potential for enhanced recovery after human CNS injury. PMID- 11201743 TI - Maize yellow stripe1 encodes a membrane protein directly involved in Fe(III) uptake. AB - Frequently, crop plants do not take up adequate amounts of iron from the soil, leading to chlorosis, poor yield and decreased nutritional quality. Extremely limited soil bioavailability of iron has led plants to evolve two distinct uptake strategies: chelation, which is used by the world's principal grain crops; and reduction, which is used by other plant groups. The chelation strategy involves extrusion of low-molecular-mass secondary amino acids (mugineic acids) known as 'phytosiderophores' which chelate sparingly soluble iron. The Fe(III) phytosiderophore complex is then taken up by an unknown transporter at the root surface. The maize yellow stripe1 (ys1) mutant is deficient in Fe(III) phytosiderophore uptake, therefore YS1 has been suggested to be the Fe(III) phytosiderophore transporter. Here we show that ys1 is a membrane protein that mediates iron uptake. Expression of YS1 in a yeast iron uptake mutant restores growth specifically on Fe(III)-phytosiderophore media. Under iron-deficient conditions, ys1 messenger RNA levels increase in both roots and shoots. Cloning of ys1 is an important step in understanding iron uptake in grasses, and has implications for mechanisms controlling iron homeostasis in all plants. PMID- 11201744 TI - CD45 is a JAK phosphatase and negatively regulates cytokine receptor signalling. AB - The regulation of tyrosine phosphorylation and associated signalling through antigen, growth-factor and cytokine receptors is mediated by the reciprocal activities of protein tyrosine kinases and protein tyrosine phosphatases (PTPases). The transmembrane PTPase CD45 is a key regulator of antigen receptor signalling in T and B cells. Src-family kinases have been identified as primary molecular targets for CD45 (ref. 4). However, CD45 is highly expressed in all haematopoietic lineages at all stages of development, indicating that CD45 could regulate other cell types and might act on additional substrates. Here we show that CD45 suppresses JAK (Janus kinase) kinases and negatively regulates cytokine receptor signalling. Targeted disruption of the cd45 gene leads to enhanced cytokine and interferon-receptor-mediated activation of JAKs and STAT (signal transducer and activators of transcription) proteins. In vitro, CD45 directly dephosphorylates and binds to JAKs. Functionally, CD45 negatively regulates interleukin-3-mediated cellular proliferation, erythropoietin-dependent haematopoieisis and antiviral responses in vitro and in vivo. Our data identify an unexpected and novel function for CD45 as a haematopoietic JAK phosphatase that negatively regulates cytokine receptor signalling. PMID- 11201745 TI - MAD2 haplo-insufficiency causes premature anaphase and chromosome instability in mammalian cells. AB - The mitotic checkpoint protein hsMad2 is required to arrest cells in mitosis when chromosomes are unattached to the mitotic spindle. The presence of a single, lagging chromosome is sufficient to activate the checkpoint, producing a delay at the metaphase-anaphase transition until the last spindle attachment is made. Complete loss of the mitotic checkpoint results in embryonic lethality owing to chromosome mis-segregation in various organisms. Whether partial loss of checkpoint control leads to more subtle rates of chromosome instability compatible with cell viability remains unknown. Here we report that deletion of one MAD2 allele results in a defective mitotic checkpoint in both human cancer cells and murine primary embryonic fibroblasts. Checkpoint-defective cells show premature sister-chromatid separation in the presence of spindle inhibitors and an elevated rate of chromosome mis-segregation events in the absence of these agents. Furthermore, Mad2+/- mice develop lung tumours at high rates after long latencies, implicating defects in the mitotic checkpoint in tumorigenesis. PMID- 11201746 TI - Pre-meiotic S phase is linked to reductional chromosome segregation and recombination. AB - Meiosis is initiated from G1 of the cell cycle and is characterized by a pre meiotic S phase followed by two successive nuclear divisions. The first of these, meiosis I, differs from mitosis in having a reductional pattern of chromosome segregation. Here we show that meiosis can be initiated from G2 in fission yeast cells by ectopically activating the meiosis-inducing network. The subsequent meiosis I occurs without a pre-meiotic S phase and with decreased recombination, and exhibits a mitotic pattern of equational chromosome segregation. The subsequent meiosis II results in random chromosome segregation. This behaviour is similar to that observed in cells lacking the meiotic cohesin Rec8 (refs 3, 4), which becomes associated with chromosomes at G1/S phase, including the inner centromere, a region that is probably critical for sister-centromere orientation. If the expression of Rec8 is delayed to S phase/G2, then the centromeres behave equationally. We propose that the presence of Rec8 in chromatin is required at the pre-meiotic S phase to construct centromeres that behave reductionally and chromosome arms capable of a high level of recombination, and that this explains why meiosis is initiated from G1 of the cell cycle. PMID- 11201747 TI - Role for a bidentate ribonuclease in the initiation step of RNA interference. AB - RNA interference (RNAi) is the mechanism through which double-stranded RNAs silence cognate genes. In plants, this can occur at both the transcriptional and the post-transcriptional levels; however, in animals, only post-transcriptional RNAi has been reported to date. In both plants and animals, RNAi is characterized by the presence of RNAs of about 22 nucleotides in length that are homologous to the gene that is being suppressed. These 22-nucleotide sequences serve as guide sequences that instruct a multicomponent nuclease, RISC, to destroy specific messenger RNAs. Here we identify an enzyme, Dicer, which can produce putative guide RNAs. Dicer is a member of the RNase III family of nucleases that specifically cleave double-stranded RNAs, and is evolutionarily conserved in worms, flies, plants, fungi and mammals. The enzyme has a distinctive structure, which includes a helicase domain and dual RNase III motifs. Dicer also contains a region of homology to the RDE1/QDE2/ARGONAUTE family that has been genetically linked to RNAi. PMID- 11201748 TI - A model for SOS-lesion-targeted mutations in Escherichia coli. AB - The UmuD'2C protein complex (Escherichia coli pol V) is a low-fidelity DNA polymerase (pol) that copies damaged DNA in the presence of RecA, single-stranded DNA binding protein (SSB) and the beta,gamma-processivity complex of E. coli pol III (ref. 4). Here we propose a model to explain SOS-lesion-targeted mutagenesis, assigning specific biochemical functions for each protein during translesion synthesis. (SOS lesion-targeted mutagenesis occurs when pol V is induced as part of the SOS response to DNA damage and incorrectly incorporates nucleotides opposite template lesions.) Pol V plus SSB catalyses RecA filament disassembly in the 3' to 5' direction on the template, ahead of the polymerase, in a reaction that does not involve ATP hydrolysis. Concurrent ATP-hydrolysis-driven filament disassembly in the 5' to 3' direction results in a bidirectional stripping of RecA from the template strand. The bidirectional collapse of the RecA filament restricts DNA synthesis by pol V to template sites that are proximal to the lesion, thereby minimizing the occurrence of untargeted mutations at undamaged template sites. PMID- 11201749 TI - Chi-sequence recognition and DNA translocation by single RecBCD helicase/nuclease molecules. AB - Major pathways of recombinational DNA repair in Escherichia coli require the RecBCD protein--a heterotrimeric, ATP-driven, DNA translocating motor enzyme. RecBCD combines a highly processive and exceptionally fast helicase (DNA unwinding) activity with a strand-specific nuclease (DNA-cleaving) activity (refs 1, 2 and references therein). Recognition of the DNA sequence 'chi' (5'-GCTGGTGG 3') switches the polarity of DNA cleavage and stimulates recombination at nearby sequences in vivo. Here we attach microscopic polystyrene beads to biotin-tagged RecD protein subunits and use tethered-particle light microscopy to observe translocation of single RecBCD molecules (with a precision of up to approximately 30 nm at 2 Hz) and to examine the mechanism by which chi modifies enzyme activity. Observed translocation is unidirectional, with each molecule moving at a constant velocity corresponding to the population-average DNA unwinding rate. These observations place strong constraints on possible movement mechanisms. Bead release at chi is negligible, showing that the activity modification at chi does not require ejection of the RecD subunit from the enzyme as previously proposed; modification may occur through an unusual, pure conformational switch mechanism. PMID- 11201750 TI - Processive translocation and DNA unwinding by individual RecBCD enzyme molecules. AB - RecBCD enzyme is a processive DNA helicase and nuclease that participates in the repair of chromosomal DNA through homologous recombination. We have visualized directly the movement of individual RecBCD enzymes on single molecules of double stranded DNA (dsDNA). Detection involves the optical trapping of solitary, fluorescently tagged dsDNA molecules that are attached to polystyrene beads, and their visualization by fluorescence microscopy. Both helicase translocation and DNA unwinding are monitored by the displacement of fluorescent dye from the DNA by the enzyme. Here we show that unwinding is both continuous and processive, occurring at a maximum rate of 972 +/- 172 base pairs per second (0.30 microm s( 1)), with as many as 42,300 base pairs of dsDNA unwound by a single RecBCD enzyme molecule. The mean behaviour of the individual RecBCD enzyme molecules corresponds to that observed in bulk solution. PMID- 11201751 TI - Crystal structure of the transcription activator BmrR bound to DNA and a drug. AB - The efflux of chemically diverse drugs by multidrug transporters that span the membrane is one mechanism of multidrug resistance in bacteria. The concentrations of many of these transporters are controlled by transcription regulators, such as BmrR in Bacillus subtilis, EmrR in Escherichia coli and QacR in Staphylococcus aureus. These proteins promote transporter gene expression when they bind toxic compounds. BmrR activates transcription of the multidrug transporter gene, bmr, in response to cellular invasion by certain lipophilic cationic compounds (drugs). BmrR belongs to the MerR family, which regulates response to stress such as exposure to toxic compounds or oxygen radicals in bacteria. MerR proteins have homologous amino-terminal DNA-binding domains but different carboxy-terminal domains, which enable them to bind specific 'coactivator' molecules. When bound to coactivator, MerR proteins upregulate transcription by reconfiguring the 19 base-pair spacer found between the -35 and -10 promoter elements to allow productive interaction with RNA polymerase. Here we report the 3.0 A resolution structure of BmrR in complex with the drug tetraphenylphosphonium (TPP) and a 22 base-pair oligodeoxynucleotide encompassing the bmr promoter. The structure reveals an unexpected mechanism for transcription activation that involves localized base-pair breaking, and base sliding and realignment of the -35 and -10 operator elements. PMID- 11201752 TI - Synthesizing life. PMID- 11201753 TI - Modelling cellular behaviour. PMID- 11201754 TI - Pasteur's Quadrant and malnutrition. PMID- 11201755 TI - Actions from thoughts. PMID- 11201756 TI - The relationship between matter and life. PMID- 11201757 TI - Life's lessons in design. PMID- 11201758 TI - Earth systems engineering and management. PMID- 11201759 TI - Interfering for the good of a chemical reaction. PMID- 11201760 TI - Future optical and infrared telescopes. PMID- 11201761 TI - New physics with the Compact Linear Collider. PMID- 11201762 TI - Health, productivity, and occupational medicine. PMID- 11201763 TI - Health and productivity management: establishing key performance measures, benchmarks, and best practices. AB - Major areas considered under the rubric of health and productivity management (HPM) in American business include absenteeism, employee turnover, and the use of medical, disability, and workers' compensation programs. Until recently, few normative data existed for most HPM areas. To meet the need for normative information in HPM, a series of Consortium Benchmarking Studies were conducted. In the most recent application of the study, 1998 HPM costs, incidence, duration, and other program data were collected from 43 employers on almost one million workers. The median HPM costs for these organizations were $9992 per employee, which were distributed among group health (47%), turnover (37%), unscheduled absence (8%), nonoccupational disability (5%), and workers' compensation programs (3%). Achieving "best-practice" levels of performance (operationally defined as the 25th percentile for program expenditures in each HPM area) would realize savings of $2562 per employee (a 26% reduction). The results indicate substantial opportunities for improvement through effective coordination and management of HPM programs. Examples of best-practice activities collated from on-site visits to "benchmark" organizations are also reviewed. PMID- 11201764 TI - Alternative valuations of work loss and productivity. AB - In this article, we examine the indirect costs (i.e., work loss and productivity costs) of employee illness from the employer's perspective. We provide a conceptual framework to help employers consider alternative views with regard to assessing indirect costs and valuing the health care they purchase. First, we discuss the matter of perspective and how an employer should view and assess indirect costs. We briefly review current models of measuring indirect costs, and we critique these models. Then we introduce a simple, conceptual framework based on the ideas of health capital and labor productivity, and we lay out the effects of health investment on indirect costs while considering what employees desire and employers can provide. Finally, we offer an agenda for further research. PMID- 11201765 TI - Depression and work productivity: the comparative costs of treatment versus nontreatment. AB - This article discusses the impact of depression on work productivity and the potential for improved work performance associated with effective treatment. We undertook a review of the literature by means of a computer search using the following key terms: cost of illness, work loss, sickness absence, productivity, performance, and disability. Published works were considered in four categories: (1) naturalistic cross-sectional studies that found greater self-reported work impairment among depressed workers; (2) naturalistic longitudinal studies that found a synchrony of change between depression and work impairment; (3) uncontrolled treatment studies that found reduced work impairment with successful treatment; and (4) controlled trials that usually, but not always, found greater reduction in work impairment among treated patients. Observational data suggest that productivity gains following effective depression treatment could far exceed direct treatment costs. Randomized effectiveness trials are needed before we can conclude definitively that depression treatment results in productivity improvements sufficient to offset direct treatment costs. PMID- 11201766 TI - The impact of a worksite health promotion program on short-term disability usage. AB - This study examined the impact of a worksite health promotion program on short term disability (STD) days in a large telecommunications company. The evaluation used a quasi-experimental, multiple time-series design with between-group comparison of workdays lost due to STD to determine impact. The study period was 3 years and included 1628 employees on STD leave. Self-selected program participants were compared with non-participants on net days lost at three assessment points: the year before the launch of the program, and each of 2 years post-launch. A comprehensive health promotion program was developed to reduce health care costs, improve employee satisfaction, and enhance the employer's image. Key features of the program included reimbursement for employees participating in the Health Risk Assessment and in wellness or fitness activities. Other features included occupational health services, targeted interventions for high-risk employees, self-care materials, and a nurse advice line. Results revealed no significant differences at baseline between participants and non-participants for net days lost while on STD leave. At the post-program launch, non-participants' net days lost significantly increased from 33.2 to 38.1 when controlled for age, gender, job type, tenure, and STD category, whereas the participant group average net days lost decreased from 29.2 to 27.8. After adjusting for baseline differences, we found a 6-day difference between groups, which represented a 20% program impact. This study found that participation in a health promotion reimbursement program had a significant impact on average net days lost for employee STD absence. These findings represented potential savings in excess of $1,371,600 over a 2-year period. Future program evaluation efforts will address the impact on medical care costs related to program participation. PMID- 11201767 TI - Health and productivity: a role for occupational health professionals. AB - The impressive economic gains achieved by many nations within the past decade have been attributed primarily to improvements in productivity from technological changes. The resultant low unemployment levels, however, emphasize the importance of human capital in the success of any enterprise. Concurrently, some economists have proposed an alternative economic view regarding the relationship between health and income, postulating that improvements in the health of the nation's population have a substantial effect on its economic viability. Such a view directly pertains to occupational health professionals, who are often charged with promoting the health of the worker. Although studies relating the beneficial impact of occupational health on productivity and human performance are limited, some efforts have shown impressive effects, as measured primarily by reduced absenteeism. The prompt, assertive management of occupational injuries and illnesses and their treatment have been well documented. Illnesses not considered traditional occupational ailments, such as migraine headaches, allergic disorders, infectious diseases, and depression, offer opportunities for occupational health professionals to ensure an accurate diagnosis and proper treatment for minimizing the impact on work performance. Considerable opportunities exist for occupational health professionals to demonstrate the importance of certain services to productivity. PMID- 11201768 TI - Health promotion programs, modifiable health risks, and employee absenteeism. AB - This literature review demonstrates that the health risks and failure of employees to participate in fitness and health promotion programs are associated with higher rates of employee absenteeism. When determining how to manage absenteeism, employers should carefully consider the impact that health promotion programs can have on rates of absenteeism and other employee-related expenses. PMID- 11201769 TI - Health, safety, and productivity in a manufacturing environment. AB - The Health and Productivity Management model at International Truck and Engine Corporation includes the measurement, analysis, and management of the individual component programs affecting employee safety, health, and productivity. The key to the success of the program was the iterative approach used to identify the opportunities, develop interventions, and achieve targets through continuous measurement and management. In addition, the integration of multiple disciplines and the overall emphasis on employee productivity and its cost are key foci of the International Model. The program was instituted after economic and clinical services' analyses of data on International employees showed significant excess costs and a high potential for health care cost reductions based on several modifiable health risk factors. The company also faced significant challenges in the safety, workers' compensation, and disability areas. The program includes safety, workers' compensation, short-term disability, long-term disability, health care, and absenteeism. Monthly reports/analyses are sent to senior management, and annual goals are set with the board of directors. Economic impact has been documented in the categories after intervention. For example, a comprehensive corporate wellness effort has had a significant impact in terms of reducing both direct health care cost and improving productivity, measured as absenteeism. Workers' compensation and disability program interventions have had an impact on current costs, resulting in a significant reduction of financial liability. In the final phase of the program, all direct and indirect productivity costs will be quantified. The impact of the coordinated program on costs associated with employee health will be analyzed initially and compared with a "silo" approach. PMID- 11201770 TI - Impact of illness and its treatment on workplace costs: regulatory and measurement issues. AB - In an attempt to document a broader spectrum of the benefits of their pharmaceutical products, drug companies increasingly seek to include productivity claims in their promotional campaigns. We describe the existing regulatory framework of the Food and Drug Administration (FDA) for considering productivity claims, distinguishing between the traditional "substantial evidence" standard and the "competent and reliable scientific evidence" standard. But the notion of competent and reliable scientific evidence may itself be problematic, even when it is the appropriate regulatory standard, because there exists no consistent measurement approach across diseases, workplaces, jobs, and worker capabilities that is widely accepted in this emerging area of health outcomes research. We examine the various measurement approaches that have been used to quantify the impact of illness and its treatment on workplace productivity, and we describe some of the shortcomings associated with each alternative. This discussion highlights the possible difficulties faced by the FDA in reviewing productivity based promotional claims. Finally, we suggest possible strategies for furthering this field of investigation. PMID- 11201771 TI - The impact of allergies and allergy treatment on worker productivity. AB - Allergic disorders are a chronic and highly prevalent condition in the general population and the workforce. Their effect on workers and corporate costs go beyond the direct cost of treatment, as the condition can lower a worker's productivity. Previous research includes estimates of the decrease in productivity associated with allergic disorders. None of these studies, however, offered an objective measure of how worker productivity is affected by allergic disorders. In the present study, the productivity of telephone customer service representatives suffering from allergic disorders is examined before, during, and after the ragweed pollen season. In addition, these workers were surveyed as to the type of medication they used in response to their condition. A significant correlation was observed between an increase in pollen counts and a decrease in productivity for workers with allergies. Compared with workers without allergies, employees with allergies who reported using no medication showed a 10% decrease in productivity. No differences were observed among workers with allergies using different types of medications, although the medication groups had significantly higher productivity than the no-medication group. The expected lowered productivity of those workers with allergies who used sedating antihistamines may have been offset by their relatively lower level of symptom severity and by the nature of the job and the productivity measures used. PMID- 11201772 TI - Laser in situ keratomileusis to correct residual myopia after cataract surgery. AB - PURPOSE: To evaluate the effectiveness, predictability, and safety of laser in situ keratomileusis (LASIK) for correcting residual myopia after cataract surgery with intraocular lens implantation. METHODS: Twenty-two eyes of 22 patients underwent LASIK for the correction of residual myopia after cataract surgery. LASIK was carried out using the Chiron Automated Corneal Shaper and the NIDEK EC 5000 excimer laser. In all eyes, the follow-up was 12 months. RESULTS: Before LASIK, 1 eye (4.5%) had an uncorrected visual acuity of 0.5 or better; 12 months after LASIK, 10 eyes (45.4%) achieved this level of visual acuity and 0 eyes achieved 1.00 or better. Before LASIK, mean refraction was -2.90 +/- 1.80 D; 12 months after LASIK it decreased significantly to 0.40 +/- 0.60 D (P < .01). In 18 eyes (81.8%) at 12 months after LASIK, spherical equivalent refraction was within +/-1.00 D of emmetropia; 11 eyes (50%) were within 0.50 D. No vision-threatening complications occurred. CONCLUSION: LASIK with the Automated Corneal Shaper and Nidek EC-5000 excimer laser was an effective, predictable, stable, and safe procedure for correcting residual myopia after cataract surgery. No intraocular lens or cataract incision related complications occurred when LASIK was performed at least 3 months after phacoemulsification. PMID- 11201773 TI - Corneal sensitivity and some properties of the tear film after laser in situ keratomileusis. AB - PURPOSE: To investigate central corneal sensitivity, lipid layer structure of the precorneal tear film, and tear volume after laser in situ keratomileusis (LASIK). METHODS: Central corneal sensitivity was measured using the Non-Contact Corneal Aesthesiometer. The aesthesiometer was mounted on a slit lamp and an airpulse of controlled pressure was directed onto the cornea. When central corneal sensitivity was reduced, a higher air pulse pressure was required to stimulate the cornea. The final central corneal sensitivity threshold measured was recorded in millibars. Tear lipid layer structure was assessed by optical interferometry and classified according to appearance using the Keeler Tearscope. Tear volume was measured using the phenol red cotton thread test. Subjects were recruited from a group of patients after LASIK who had experienced no complications (n=22). The average postoperative time was 14 weeks and measurements were taken on one eye. In bilateral cases, measurements were recorded from the right eye only. Average attempted correction was -6.30 D (range, -2 to -11 D). Age-matched controls were later recruited for central corneal sensitivity threshold (n=24). A second group of age-matched controls were recruited for tear volume and lipid layer structure (n=24). RESULTS: The median (range) was 1.1 mbars (0.2 to 4.3 mbars) after LASIK and 0.58 mbars (0.20 to 1.3 mbars) in the controls; the difference was statistically significant (P = .043). The lipid layer of the tear film tended to be thinner in eyes after LASIK compared with controls (P = .032). The mean (+/- SD) tear volume was 16.9 +/- 8.3 mm after LASIK and 19.8 +/- 7.1 mm in controls. This difference was not statistically significant (P = .492). CONCLUSION: At 14 weeks postoperatively, central corneal sensitivity was below normal levels and the tear lipid layer was thinner. The poorer quality lipid layer may predispose to symptoms of dry eye after LASIK. PMID- 11201774 TI - Intrastomal corneal ring segments: reversibility of refractive effect. AB - PURPOSE: To evaluate the reversibility of refractive effect following removal of the ICRS (intrastromal corneal ring segments; Intacs). METHODS: Data from 34 eyes from which ICRS were removed during United States FDA Phase II and III clinical trials were evaluated with regard to segment size, loss or change of best spectacle-corrected visual acuity (BSCVA), any change of uncorrected visual acuity (UCVA), manifest spherical equivalent refraction, manifest cylinder refraction, stability of manifest cylinder refraction, and subjective visual symptoms. RESULTS: Out of 725 initial or contralateral eyes placed with the ICRS during Phase II and III clinical trials, segments were removed from 34 eyes (4.7%). Other than one (1/725, 0.1%) safety related ICRS removal, 30/725 (4.1%) were due to visual symptoms. ICRS removal was accomplished under topical anesthesia without complications in all eyes. The mean length of time the segments remained in the cornea after initial surgery was 10.3 +/- 5.4 months. At 3 months after ICRS removal, 21 eyes had monitored data available and were within +/-1 line or 10 letters of their preoperative BSCVA. Twenty eyes (20/21, 95%) returned to within +/-1.00 D of their preoperative manifest spherical equivalent refraction. All eyes had a stable refraction at the 3-month examination after removal, and a manifest spherical equivalent refraction within +/-1.00 D of their 1-month examination after removal. Nineteen eyes (19/21, 90%) returned to within +/-2 lines and 16 eyes (16/21, 76%) returned to within +/-1 line of preoperative UCVA. CONCLUSION: The ICRS (Intacs) was easily and safely removed, and eyes returned to preoperative refractive status within 3 months. PMID- 11201775 TI - Posterior chamber phakic intraocular lenses to correct high myopia: a comparative study between Staar and Adatomed models. AB - PURPOSE: To determine the feasibility of using posterior chamber phakic intraocular lenses (PIOLs) to treat high myopia, comparing two different models, Staar and Adatomed. METHODS: Twenty-four eyes from 12 patients were studied prospectively. A phakic Staar IOL was implanted in one eye of each patient, and the other eye received a phakic Adatomed IOL. Patients with uveitis or ocular trauma prior to ocular surgery, diabetic retinopathy, or capsular pseudoexfoliation were excluded. The mean preoperative spherical equivalent refraction was -16.00 +/- 5.05 D for the Staar group and -15.39 +/- 2.83 D for the Adatomed group. Average follow-up was 32.4 months (range, 19 to 46 mo) for the Adatomed group and 18.3 months (range, 11 to 21 mo) for the Staar group and included evaluation of intraocular pressure, intraocular lens pigment deposits, lens decentration, anterior subcapsular cataract, and visual acuity. RESULTS: Spectacle-corrected and uncorrected visual acuity improved in all eyes in both groups. No statistically significant differences in visual acuity gain were observed with the two materials (Student t-test, P = .08 for the Staar group and P = .6 for the Adatomed group), although the gain in visual acuity was somewhat greater with the Staar PIOLs. The difference in mean intraocular pressure before surgery and at last follow-up was 1.5 mmHg for the Staar group and 2.3 mmHg for the Adatomed group (P = .36). The incidence of lens pigment deposits was the same in both groups (41.66%), with deposits in 5 of the 12 eyes in both groups. The incidence of lens decentration was higher in the Adatomed group (5/12; 41.66%) than in the Staar group (2/12; 16.7%). Anterior subcapsular cataract was higher in the Adatomed group (4/12; 33.3%) than in the Staar group (3/12; 25%). CONCLUSIONS: There was a higher incidence of lens decentration and anterior subcapsular cataract in the Adatomed group than in the Staar group. PMID- 11201776 TI - Smoothness of ablation on acrylic by four different excimer lasers. AB - PURPOSE: There are many different excimer laser devices available for photoablative refractive surgery. Smoothness of ablation may vary with different excimer lasers systems. METHODS: Ablations were performed on polymethylmethacrylate (PMMA) plates of 8 x 4 x 0.5 cm, with four different excimer lasers: VISX-Star, Coherent Schwind Keratom I/II, Chiron Technolas Keracor 117C (Plano Scan), and the Nidek EC-5000, to determine and compare the homogeneity and smoothness of the surface. Ten -3.00 D samples, ten -6.00 D samples, and ten -9.00 D samples were ablated with each laser. The PMMA discs were examined with optical microscopy, documented by photographs, and each sample was measured quantitatively using a Hommel-Werkel rugosimeter. We used the same PMMA material throughout. RESULTS: Statistically significant differences in smoothness were found between the Chiron Technolas 117C and the VISX-Star, Nidek and VISX-Star, and Coherent Schwind and VISX-Star in the homogeneities achieved by ablating -3.00 D. Ablations of -6.00 D resulted in homogeneities that were statistically significantly different: Chiron Technolas 117C with the other three devices, the Nidek EC-5000 with the VISX-Star, and the Coherent-Schwind with the VISX-Star. In the ablations for -9.00 D, statistically significant differences in homogeneity were found between the Chiron Technolas 117C and Nidek, between the Chiron and VISX-Star, between the Coherent Schwind and VISX-Star, and between the Nidek and VISX-Star. The laser with the scanning spot system was smoother. CONCLUSION: Scanning spot technology produced smooth ablations even up to -9.00 D. PMID- 11201777 TI - Comparison of laser in situ keratomileusis and photorefractive keratectomy for the correction of myopia of -6.00 diopters or less. Melbourne Excimer Laser Group. AB - PURPOSE: To evaluate the safety and efficacy of laser in situ keratomileusis (LASIK) compared to photorefractive keratectomy (PRK) for the correction of low or moderate myopia (-0.50 to -6.00 D) at 6 months after surgery. METHODS: The study population comprised a non-randomized consecutive series of 622 eyes of 392 patients who were treated with the Nidek EC-5000 excimer laser. LASIK was performed using the ACS Chiron microkeratome on 314 eyes and surface PRK on 308 eyes. All patients were treated using a standard protocol, then assessed at 1, 3, and 6 months postoperatively. RESULTS: Forty-four percent of the LASIK group and 67% of the PRK group attended their 6-month examination. Eighty percent of patients (111 eyes) after LASIK and 65% (136 eyes) after PRK had an uncorrected visual acuity of 20/20 or better. Spherical equivalent refraction was within +/ 0.50 D of intended refraction in 78% (109 eyes) for LASIK and 82% (170 eyes) for PRK. Loss of two more lines of best spectacle-corrected visual acuity at 6 months occurred in 1.4% (2 eyes) of the LASIK group and 1.0% (2 eyes) of the PRK group. CONCLUSION: At 1 month follow-up, the percentage of eyes that achieved 20/20 uncorrected visual acuity was greater in the LASIK group than in the PRK group. At 6 months, visual and refractive outcomes of LASIK and PRK were similar. Although flap related complications occurred only after LASIK, the overall risk of loss of best spectacle-corrected visual acuity was not significantly greater than for PRK. PMID- 11201779 TI - Treatment of progressive or recurrent epithelial ingrowth with ethanol following laser in situ keratomileusis. AB - PURPOSE: To evaluate the use of ethanol in the treatment of progressive or recurrent epithelial ingrowth following laser in situ keratomileusis (LASIK). METHODS: Four eyes of four patients with aggressive epithelial ingrowth following LASIK underwent epithelial ingrowth removal with 50% ethanol. Aggressive epithelial ingrowth was defined as, 1) progressive enlargement on serial examination with an area of ingrowth involving at least 30% of the flap surface area, 2) epithelial ingrowth associated with stromal melting as evidence on clinical or topographic examination, or 3) recurrent epithelial ingrowth in the same area following previous removal. RESULTS: Epithelial ingrowth was removed successfully in all eyes. No eye lost best spectacle-corrected visual acuity. One eye with multiple risk factors for failure experienced nonprogressive recurrence. No eyes required reoperation for recurrent epithelial ingrowth. No eyes experienced progression of stromal melt. Regularization of corneal topography was observed in an eye with preoperative stromal melting. The only complication was a tendency for the development of diffuse lamellar keratitis. Two eyes (50%) experienced diffuse lamellar keratitis following epithelial ingrowth removal with ethanol, which resolved completely with topical corticosteroids. CONCLUSION: Ethanol may be a useful adjunct in the treatment of aggressive or recurrent epithelial ingrowth following LASIK. Cautious use with the lowest concentration of ethanol may prove useful in these difficult epithelial ingrowth cases. Randomized and prospective studies are recommended to evaluate our experience. PMID- 11201778 TI - Perioperative microbiologic profile of the conjunctiva in photorefractive keratectomy. AB - PURPOSE: Therapeutic soft contact lenses are used commonly as an adjunctive treatment after photorefractive keratectomy (PRK) to decrease postoperative pain caused by the movement of lids over the corneal epithelial defect and to facilitate epithelial healing. We assessed the microbiological profile of the conjunctiva of patients undergoing PRK for myopia, before and after the concurrent use of a therapeutic soft contact lens, and compared the effect on ocular bacterial colonization of prophylactic administration of topical tobramycin 0.3% versus ofloxacin 0.3%. METHODS: Forty-three consecutive eyes from 37 patients underwent PRK for myopia or myopic astigmatism. Eyes were assigned randomly to prophylactic antibacterial treatment with either topical ofloxacin 0.3% or tobramycin 0.3%, applied prior to surgery and three times daily after surgery until therapeutic soft contact lens removal. Material from the conjunctival sac was obtained for bacteriologic cultures prior to surgery. Clinical evaluation of all eyes was conducted prospectively. Three days after PRK, the therapeutic soft contact lenses were removed and cultured. Cultures from the conjunctival sac were then repeated. RESULTS: No statistically significant differences were observed in culture positivity between the two groups of eyes, in spite of some positive preoperative and postoperative cultures. Only one out of 43 eyes (assigned to the ofloxacin group) developed a peripheral corneal infiltrate. The corneal infiltrate healed completely without sequelae using antibiotic and corticosteroid therapy. CONCLUSIONS: The use of therapeutic soft contact lenses after PRK with either topical tobramycin 0.3% or ofloxacin 0.3% were well tolerated. However, perioperative positive conjunctival cultures were relatively frequent and prophylactic antibiotics should be used in the setting of an epithelial defect and therapeutic soft contact lens following PRK. PMID- 11201780 TI - Surgical treatment of keratoconus at the turn of the 20th century. AB - PURPOSE: This paper reviews surgical modalities for treatment of keratoconus at the threshold of the 20th century. METHODS: All ophthalmic literature from 1895 until 1925 in English and German, available at the library of the Institute of Ophthalmology, London, United Kingdom, was studied with respect to this topic. RESULTS: Three thermal procedures were described; galvanocauterization with perforation, without perforation, and a non-contact application of heat to the corneal apex. Radial extension of a thermal burn to correct the minus cylinder represented a further modification. Excision of the conical area was suggested either as a lamellar dissection or as a full thickness trephination. Incision of the cone appeared to be less popular. In staged procedures, a combination of galvanocauterization, splitting of the cornea, conjunctival flap, and a subsequent optical iridectomy were applied. CONCLUSION: The treatment of keratoconus 100 years ago used refractive surgery to improve visual function by modifying corneal shape. PMID- 11201781 TI - Sabine Dausch awarded Troutman Prize for 2000. PMID- 11201782 TI - The cornea is not a piece of plastic. PMID- 11201783 TI - The cornea is not a piece of plastic. PMID- 11201784 TI - The cornea is not a piece of plastic. PMID- 11201785 TI - Cell adhesion/recognition and signal transduction through glycosphingolipid microdomain. AB - Glycosphingolipids (GSLs) and sphingomyelin in animal cells are clustered and organized as membrane microdomains closely associated with various signal transducer molecules such as cSrc, Src family kinases, small G-proteins (e.g., RhoA, Ras), and focal adhesion kinase. GSL clustering in such microdomains causes adhesion to complementary GSLs on the surface of counterpart cells or presented on plastic surfaces, through carbohydrate-to-carbohydrate interaction. GSL dependent cell adhesion in microdomain causes activation of the signal transducers, leading to cell phenotypic changes. A retrospective of the development of this concept, and current status of our studies, are presented. PMID- 11201786 TI - Functional roles of glycosphingolipids in signal transduction via lipid rafts. AB - The formation of glycosphingolipid (GSL)-cholesterol microdomains in cell membranes has been proposed to function as platforms for the attachment of lipid modified proteins, such as glycosylphosphatidylinositol (GPI)-anchored proteins and src-family tyrosine kinases. The microdomains are postulated to be involved in GPI-anchored protein signaling via src-family kinase. Here, the functional roles of GSLs in signal transduction mediated by the microdomains are discussed. Antibodies against GSLs co-precipitate GPI-anchored proteins, src-family kinases and several components of the microdomains. Antibody-mediated crosslinking of GSLs, as well as that of GPI-anchored proteins, induces a rapid activation of src family kinases and a transient increase in the tyrosine phosphorylation of several substrates. Enzymatic degradation of GSLs reduces the activation of src family kinase and tyrosine phosphorylation by antibody-mediated crosslinking of GPI-anchored protein. Furthermore, GSLs can also modulate signal transduction of immunoreceptors and growth factor receptors in the microdomains. Thus, GSLs have important roles in signal transduction mediated by the microdomains. PMID- 11201788 TI - Glycosphingolipid (GSL) microdomains as attachment platforms for host pathogens and their toxins on intestinal epithelial cells: activation of signal transduction pathways and perturbations of intestinal absorption and secretion. AB - Glycosphingolipid (GSL)-enriched microdomains are used as cellular binding sites for various pathogens including viruses and bacteria. These attachment platforms are specifically associated with transducer molecules, so that the binding of host pathogens (or their toxins) to the cell surface may result in the activation of signal transduction pathways. In the intestinal epithelium, such pathogen induced dysregulations of signal transduction can elicit a severe impairment of enterocytic functions. In this study, we demonstrate that the interaction of a bacterial toxin (cholera toxin) and a viral envelope glycoprotein (HIV-1 gp120) with the apical plasma membrane of intestinal cells is mediated by GSL-enriched microdomains that are associated with G regulatory proteins. These microbial proteins induce a GSL-dependent increase of intestinal fluid secretion by two mechanisms: activation of chloride secretion and inhibition of Na+ -dependent glucose absorption. Taken together, these data support the view that GSL-enriched microdomains in the apical plasma membrane of enterocytes are involved in the regulation of intestinal functions. PMID- 11201787 TI - Lipid membrane domains in cell surface and vacuolar systems. AB - Detergent insoluble sphingolipid-cholesterol enriched 'raft'-like membrane microdomains have been implicated in a variety of biological processes including sorting, trafficking, and signaling. Mutant cells and knockout animals of sphingolipid biosynthesis are clearly useful to understand the biological roles of lipid components in raft-like domains. It is suggested that raft-like domains distribute in internal vacuolar membranes as well as plasma membranes. In addition to sphingolipid-cholesterol-rich membrane domains, recent studies suggest the existence of another lipid-membrane domain in the endocytic pathway. This domain is enriched with a unique phospholipid, lysobisphosphatidic acid (LBPA) and localized in the internal membrane of multivesicular endosome. LBPA rich membrane domains are involved in lipid and protein sorting within the endosomal system. Possible interaction between sphingolipids and LBPA in sphingolipid-storage disease is discussed. PMID- 11201789 TI - On the biogenesis of the myelin sheath: cognate polarized trafficking pathways in oligodendrocytes. AB - Oligodendrocytes, the myelinating cells of the central nervous system, are capable of transporting vast quantities of proteins and of lipids, in particular galactosphingolipids, to the myelin sheath. The sheath is continuous with the plasma membrane of the oligodendrocyte, but the composition of both membrane domains differs substantially. Given its high glycosphingolipid and cholesterol content the myelin sheath bears similarity to the lipid composition of the apical domain of a polarized cell. The question thus arises whether myelin components, like typical apical membrane proteins are transported by an apical-like trafficking mechanism to the sheath, involving a 'raft'-mediated mechanism. Indeed, the evidence indicates the presence of cognate apical and basolateral pathways in oligodendrocytes. However, all major myelin proteins do not participate in this pathway, and remarkably apical-like trafficking seems to be restricted to the oligodendrocyte cell body. In this review, we summarize the evidence on the existence of different trafficking pathways in the oligodendrocyte, and discuss possible mechanisms separating the oligodendrocyte's membrane domains. PMID- 11201791 TI - Role of glycosphingolipid microdomains in CD4-dependent HIV-1 fusion. AB - The fusion of HIV-1 with the plasma membrane of CD4+ cells is triggered by the interaction of HIV-1 surface envelope glycoprotein gp120 with the CD4 receptor, and requires coreceptors (CCR5 and CXCR4). Recent advances in the study of HIV-1 entry into CD4+ cells suggest that glycosphingolipids (GSL) may also participate in the fusion process. GSL are organized in functional microdomains which are associated with specific membrane proteins such as CD4. GSL-enriched microdomains were purified from human lymphocytes and reconstituted as a monomolecular film at the air-water interface of a Langmuir film balance. Surface pressure measurements allowed to characterize the sequential interaction of GSL with CD4 and with gp120. Using this approach, we identified globotriaosylceramide (Gb3) and ganglioside GM3 as the main lymphocyte GSL recognized by gp120. In both cases, the interaction was saturable and dramatically increased by CD4. We propose that GSL microdomains behave as moving platforms allowing the recruitment of HIV-1 coreceptors after the initial interaction between the viral particle and CD4. According to this model, the GSL microdomain may: i) stabilize the attachment of the virus with the cell surface through multiple low affinity interactions between the V3 domain of gp120 and the carbohydrate moiety of GSL, and ii) convey the virus to an appropriate coreceptor by moving freely in the outer leaflet of the plasma membrane. This model can be extrapolated to all envelope viruses (e.g. influenza virus) that use cell surface GSL of the host cells as receptors or coreceptors. PMID- 11201790 TI - Signaling through sphingolipid microdomains of the plasma membrane: the concept of signaling platform. AB - Transmembrane signaling requires modular interactions between signaling proteins, phosphorylation or dephosphorylation of the interacting protein partners and temporary elaboration of supramolecular structures, to convey the molecular information from the cell surface to the nucleus. Such signaling complexes at the plasma membrane are instrumental in translating the extracellular cues into intracellular signals for gene activation. In the most straightforward case, ligand binding promotes homodimerization of the transmembrane receptor which facilitates modular interactions between the receptor's cytoplasmic domains and intracellular signaling and adaptor proteins. For example, most growth factor receptors contain a cytoplasmic protein tyrosine kinase (PTK) domain and ligand mediated receptor dimerization leads to cross phosphorylation of tyrosines in the receptor's cytoplasmic domains, an event that initiates the signaling cascade. In other signaling pathways where the receptors have no intrinsic kinase activity, intracellular nonreceptor PTKs (i.e. Src family PTKs, JAKs) are recruited to the cytoplasmic domain of the engaged receptor. Execution of these initial phosphorylations and their translation into efficient cellular stimulation requires concomitant activation of diverse signaling pathways. Availability of stable, preassembled matrices at the plasma membrane would facilitate scaffolding of a large array of receptors, coreceptors, tyrosine kinases and other signaling and adapter proteins, as it is the case in signaling via the T cell antigen receptor. The concept of the signaling platform has gained usage to characterize the membrane structure where many different membrane-bound components need to be assembled in a coordinated manner to carry out signaling. The structural basis of the signaling platform lies in preferential assembly of certain classes of lipids into distinct physical and functional compartments within the plasma membrane. These membrane microdomains or rafts (Figure 1) serve as privileged sites where receptors and proximal signaling molecules optimally interact. In this review, we shall discuss first how signaling platforms are assembled and how receptors and their signaling machinery could be functionally linked in such structures. The second part of our review will deal with selected examples of raft-based signaling pathways in T lymphocytes and NK cells to illustrate the ways in which rafts may facilitate signaling. PMID- 11201792 TI - Co-localization of receptor and transducer proteins in the glycosphingolipid enriched, low density, detergent-insoluble membrane fraction of sea urchin sperm. AB - The low density, detergent-insoluble membrane fraction (LD-DIM), where gangliosides are likely to be highly enriched, was prepared from sperm of two sea urchin species, Hemicentrotus pulcherrimus and Strongylocentrotus purpuratus. Immunoblotting showed the presence in the LD-DIM of two receptors for egg ligands, a glycosylphosphatidylinositol (GPI)-anchored protein, and four proteins which may be involved in signal transduction. Co-immunoprecipitation revealed that at least three proteins, the speract receptor, the 63kDa GPI-anchored protein and the alpha subunit of a heterotrimeric Gs protein, are localized in the LD-DIM. This suggests that the LD-DIM fraction may be a membrane microdomain for speract-speract receptor interaction, as well as the subsequent signal transduction pathway involved in induction of sperm respiration, motility and possibly the acrosome reaction. PMID- 11201793 TI - Use of a photoactivable GM1 ganglioside analogue to assess lipid distribution in caveolae bilayer. AB - A new photoactivable, radioactive derivative of ganglioside GM1 has been utilized to assess lipid distribution in the caveolae bilayer, taking advantage of the ability of the glycolipid, endogenous or exogenously added, to concentrate within this membrane compartment and to crosslink neighboring molecules upon illumination. After insertion into A431 plasma membrane and photoactivation, a membrane-enriched and a detergent-resistant fraction, enriched in gangliosides, sphingomyelin and cholesterol, were isolated. While a few radioactive proteins were detected in the membrane-enriched fraction, only radioactive caveolin was detected in the detergent-resistant fraction, indicating at the same time the enrichment of this fraction in caveolae and the presence of ganglioside within this compartment. Among lipids, crosslinked phosphatidylcholine, sphingomyelin and cholesterol were detected in the membrane-enriched fraction, while only crosslinked sphingomyelin was detected in the detergent-resistant fraction. These results suggest the enrichment in sphingomyelin - along with ganglioside - within the outer leaflet, and the preferential localization of cholesterol within the endoplasmic leaflet, of the caveolae bilayer. PMID- 11201794 TI - Association of Src-family protein tyrosine kinases with sphingolipids in rat cerebellar granule cells differentiated in culture. AB - Src family kinases play a relevant role in the development and differentiation of neuronal cells. They are abundant in sphingolipid-enriched membrane domains of many cell types, and these domains are hypothesized to function in bringing together molecules important to signal transduction. We studied the association of Src family tyrosine kinases and their negative regulatory kinase, Csk, with sphingolipids in sphingolipid-enriched domains of rat cerebellar granule cells differentiated in culture. We find that c-Src, Lyn and Csk are enriched in the sphingolipid-enriched fraction prepared from these cells. Coimmunoprecipitation experiments show that these and sphingolipids are part of the same domain. Cross linking experiments with a photoactivable, radioactive GD1b derivative show that c-Src and Lyn, which are anchored to the membrane via a myristoyl chain, associate directly with GD1b. Csk, which is not inserted in the hydrophobic core of the membrane, is not photolabeled by this ganglioside. These results suggest that lipid-lipid, lipid-protein, and protein-protein interactions cooperate to maintain domain structure. We hypothesize that such interactions might play a role in the process of neuronal differentiation. PMID- 11201795 TI - Unglycosylated Trk protein does not co-localize nor associate with ganglioside GM1 in stable clone of PC12 cells overexpressing Trk (PCtrk cells). AB - Our previous studies have shown that acidic glycosphingolipid, ganglioside GM1 (GM1), is an endogenous regulator of high affinity nerve growth factor receptor, Trk, which is an essential factor for the normal development and differentiation of neuronal cells by forming a complex with Trk. GM1 is also known to be a major constituent of caveola or glycosphingolipid-enriched microdomain (GEM) of the plasma membrane. In order to study the effect of the glycosylation of Trk on the formation of GM1-Trk complex and subcellular distribution of this protein, we generated PC12 cells stably overexpressing Trk (PCtrk). Pretreatment of this stable clones with tunicamycin, a potent inhibitor of N-glycosylation, caused the appearance of unglycosylated Trk core protein. These unglycosylated Trk can hardly respond to its ligand, NGF. Sucrose density gradient analysis revealed that unglycosylated Trk core protein was recovered in high density fractions, whereas most of GM1 is present in low density fractions corresponding to caveola or GEM fractions. Moreover, these unglycosylated Trk proteins lose their ability to form a complex with GM1, although GM1 is present in the same high density fractions. These data strongly suggest that spatial segregation of GM1 from the Trk protein by the inhibition of the glycosylation of Trk might be an important molecular mechanism for the unresponsiveness to NGF. Moreover, the binding site of GM1 in the Trk protein might act as an important determinant for the normal trafficking of the Trk protein within the cells. PMID- 11201796 TI - Glycosphingolipid deficiency affects functional microdomain formation in Lewis lung carcinoma cells. AB - In view of the increasing evidence that gangliosides in membrane microdomains or rafts are closely associated with various signal transducing molecules including Src family kinases, we compared rafts in two subclones of 3LL mouse lung carcinoma cell line, J18 and J5, characterized by high and very low GM3 ganglioside contents, respectively. Rafts were isolated from cell lysates as low density detergent-insoluble microdomains (DIM) by sucrose density gradient centrifugation. J5 and J18 cells expressed comparable amounts of Src family kinases and the majority of Src kinases in both clones were concentrated in their DIMs, suggesting that GM3 is not necessary for DIM localization of Src kinases and there is no direct interaction between Src and GM3. However, the Src kinases were eliminated from DIMs after depletion of the major neutral GSLs of J5 cells, glucosylceramide and lactosylceramide, by an inhibitor of glucosylceramide synthase (D-PDMP), indicating that GSLs in general are required for Src kinase association to DIM. J5 and the D-PDMP-treated J5 cells had very similar DIM protein profiles and moreover cholesterol and sphingomyelin in the GSL-depleted cells were enriched in DIM similar to the untreated control cells. Interestingly, the levels of tyrosine-phosphorylated DIM proteins and cell proliferation of J5 cells were much lower than those of J18 cells, suggesting that GM3 might be involved in tyrosine phosphorylation of DIM proteins required for cell growth. Thus, our data suggest that GSLs are essential for functional raft formation. PMID- 11201797 TI - Association between GM3 and CD4-Ick complex in human peripheral blood lymphocytes. AB - The aim of this study was to further elucidate our previous observation on molecular interaction of GM3, CD4 and p56Ick in microdomains of human peripheral blood lymphocytes (PBL). We analyzed GM3 distribution by immunoelectron microscopy and the association between GM3 and CD4-p56Ick complex by scanning confocal microscopy and co-immunoprecipitation experiments. Scanning confocal microscopy analysis showed an uneven signal distribution of GM3 molecules over the surface of human lymphocytes. Nearly complete colocalization areas indicated that CD4 molecules were distributed in GM3-enriched plasma membrane domains. Co immunoprecipitation experiments revealed that CD4 and p56Ick were immunoprecipitated by IgG anti-GM3, demonstrating that GM3 tightly binds to the CD4-p56Ick complex in human PBL. In order to verify whether GM3 association with CD4 molecules may depend on the presence of p56Ick, we analyzed this association in U937, a CD4 + and p56Ick negative cell line. The immunoprecipitation with anti GM3 revealed the presence of a 58kDa band immunostained with anti-CD4 Ab, suggesting that the GM3-CD4 interaction does not require its association with p56Ick. These findings support the view that GM3 enriched-domains may represent a functional multimolecular complex involved in signal transduction and cell activation. PMID- 11201798 TI - Changes in lipid and protein constituents of rafts and caveolae in multidrug resistant cancer cells and their functional consequences. AB - The carcinogenic process involves a complex series of genetic and biochemical changes that enables transformed cells to proliferate, migrate to secondary sites and, in some cases, acquire mechanisms that make cancer cells resistant to chemotherapy. This phenomenon in its most common form is known as multidrug resistance (MDR). It is usually mediated by overexpression of P-glycoprotein (P gp) or other plasma membrane ATPases that export cytotoxic drugs used in chemotherapy, thereby reducing their efficacy. However, additional adaptive changes are likely to be required in order to confer a full MDR phenotype. Recent studies have shown that acquisition of MDR is accompanied by upregulation of lipids and proteins that constitute lipid rafts and caveolar membranes, notably glucosylceramide and caveolin. These changes may be related to the fact that in MDR cells a significant fraction of cellular P-gp is associated with caveolin rich membrane domains, they may be involved in drug transport and they could have an impact on drug-induced apoptosis and on the phenotypic transformation of MDR cancer cells. PMID- 11201799 TI - New approaches to the study of sphingolipid enriched membrane domains: the use of electron microscopic autoradiography to reveal metabolically tritium labeled sphingolipids in cell cultures. AB - This paper is the first report on the use of the electron microscopy autoradiography technique to detect metabolically tritium labeled sphingolipids in intact cells in culture. To label cell sphingolipids, human fibroblasts in culture were fed by a 24 hours pulse, repeated 5 times, of 3 x 10(-7) M [1 (3)H]sphingosine. [1-(3)H]sphingosine was efficently taken up by the cells and very rapidly used for the biosynthesis of complex sphingolipids, including neutral glycolipids, gangliosides, ceramide and sphingomyelin. The treatment with [1-(3)H]sphingosine did not induce any morphological alteration of cell structures, and well preserved cells, plasma membranes, and intracellular organelles could be observed by microscopy. Ultrathin sections from metabolic radiolabeled cells were coated with autoradiographic emulsion. One to four weeks of exposition resulted in pictures where the location of radioactive sphingolipids was evidenced by the characteristic appearance of silver grains as irregular coiled ribbons of metallic silver. Radioactive sphingolipids were found at the level of the plasma membranes, on the endoplasmic reticulum and inside of cytoplasmic vesicles. Thus, electron microscopy autoradiography is a very useful technique to study sphingolipid-enriched membrane domain organization and biosynthesis. PMID- 11201800 TI - Mitomycin: effects on laryngeal and tracheal stenosis, benefits, and complications. AB - The management of laryngeal and tracheal stenosis continues to challenge us, despite advances in surgical techniques and better understanding of the wound healing process. Injury to the airway mucosa is the inciting event, regardless of the cause of the stenosis. Mitomycin-C is an antineoplastic antibiotic that acts as an alkylating agent by inhibiting DNA and protein synthesis. It can inhibit cell division, protein synthesis, and fibroblast proliferation. Topical application of mitomycin-C (0.4 mg/mL) was used as an adjuvant treatment in the endoscopic laser management of laryngeal and tracheal stenosis in 15 patients. Fourteen patients (93%) have shown improvement of their airway and resolution of their preoperative symptoms. After a mean follow-up of 18 months, no complication was noted with regard to the application of mitomycin-C. This study gives promising findings on the efficacy and safety of mitomycin-C as an adjuvant treatment in the management of selected cases of laryngeal and tracheal stenosis. PMID- 11201801 TI - Irreversible sensorineural hearing loss as a result of azithromycin ototoxicity. A case report. PMID- 11201802 TI - Acquired total (grade 4) subglottic stenosis in children. AB - Pediatric acquired total subglottic stenosis (SGS) is a challenging problem. The management of these patients has evolved at our institution over the past 25 years. We conducted a retrospective study to evaluate the surgical management and outcomes of children with grade 4 SGS. Fifty-six patients have presented with acquired grade 4 SGS since 1981. The causes included previous surgery (34), prolonged intubation (15), bums (1), and unknown causes (6). Of the 56 patients, 44 (79%) were decannulated; 120 total procedures were performed, and 39 patients (70%) required more than 1 procedure for decannulation. The decannulation rate has risen from 67% in the 1980s to 86% in the 1990s. Patients who underwent cricotracheal resection (CTR) had a higher decannulation rate than patients who underwent laryngotracheal reconstruction (LTR) with anterior and posterior costal cartilage grafting (CCG) (92% versus 81%), and were less likely to need additional open procedures to achieve decannulation (18% versus 46%). The decannulation rate for children with grade 4 SGS has improved because of advances in surgical technique. Currently, the principal operations used at our institution are 1) CTR and 2) LTR with anterior and posterior CCG. There was a trend toward a higher decannulation rate in patients who underwent CTR, and they were less likely to require further reconstructive surgery before decannulation. PMID- 11201803 TI - Effect of in vitro irradiation of donor larynges on cyclosporine requirements and rejection rates in rat laryngeal transplantation. AB - Total lymphoid irradiation is an acknowledged adjunctive immunosuppressant in whole organ transplantation in humans and animals. Local irradiation administered for a similar purpose is at best controversial. We evaluated in vitro donor larynx irradiation immediately preceding laryngeal transplantation as an immunomodulator. Each donor larynx was pretreated with 7.34 Gy of radiation in vitro. After transplantation, cyclosporine was administered in doses of 5 mg/kg per day, 2.5 mg/kg per day, and 1 mg/kg per day for trial lengths of 15 days and 30 days. Each of these 6 groups consisted of 10 rats per group. Earlier data have shown cyclosporine dosed at 5 mg/kg per day, without irradiation, administered for 1 month to have varied efficacy. Established histologic criteria were used to determine rejection patterns. All recipient rats survived the 15-day and 30-day trials. In all 10 rats receiving 5 mg/kg per day of cyclosporine for 15 days, the harvested transplanted larynges were viable without evidence of meaningful rejection (mild rejection). In 9 of the 10 rats receiving 5 mg/kg per day of cyclosporine for 30 days, the transplanted larynges displayed no meaningful rejection (mild rejection). In 9 of the 10 rats receiving 2.5 mg/kg per day of cyclosporine for 15 days, the transplanted larynges displayed no meaningful rejection (mild rejection). One rat receiving 2.5 mg/kg per day of cyclosporine for 15 days had a transplanted larynx that displayed moderate rejection. In all 10 rats receiving 2.5 mg/kg per day of cyclosporine for 30 days, the transplanted larynges displayed no meaningful rejection (mild rejection). At 15 days, 5 rats treated with 1 mg/kg per day of cyclosporine displayed mild rejection, 2 displayed moderate rejection, 2 displayed advanced to moderate rejection, and 1 displayed severe rejection. At 30 days, 4 rats treated with 1 mg/kg per day of cyclosporine displayed moderate rejection, 2 displayed advanced to moderate rejection, and 4 displayed severe rejection. We conclude that pretransplantation in vitro irradiation of donor larynges has immunomodulatory effects, allowing reduced cyclosporine immunosuppression with less rejection. PMID- 11201805 TI - Intraoperative assessment of stapes movement. AB - A method is described that allows, for the first time, intraoperative vibration modes assessment of the acoustically stimulated stapes by means of scanning laser Doppler interferometry (LDI). The study was designed to answer the following questions: 1) Is LDI practical for taking measurements during surgery? 2) Are the results comparable to the findings in temporal bone preparations? and 3) Do the vibration characteristics of the stapes change after the posterior incudal ligament is detached from the incus? Seven patients with profound bilateral hearing loss who were undergoing cochlear implantation were included in the study. The measurement system was easily applicable for intraoperative measurements and allowed contact-free analysis with very high accuracy. No major differences in the results from the live human subjects and temporal bone preparations were observed. The stapes movement was predominantly pistonlike at the lower frequencies and became complex at higher frequencies. Sacrificing the posterior incudal ligament had no statistically significant effect on stapes vibration. PMID- 11201804 TI - Effect of mitomycin-C on vocal fold healing in a canine model. AB - For evaluation of the effect of topical mitomycin-C on vocal fold healing and return of function after surgical excision of mucosa, 6 dogs underwent suspension microlaryngoscopy with bilateral microflap excision of vocal fold mucosa. Topical mitomycin-C, a chemotherapeutic agent and a fibroblast inhibitor, was applied randomly to one side, with the contralateral side serving as the control. Laryngeal videostroboscopy (LVS) was performed on each animal before the operation, at 2 weeks, and before sacrifice at 4 weeks. Both functional analysis with LVS and histologic analysis were performed in a blinded fashion to determine the effect of mitomycin-C on healing. Histologic analysis was augmented with computer morphometrics. The LVS revealed diminished mucosal wave vibration in the vocal folds treated with mitomycin-C, as well as a more atrophic appearance to the vibratory surface. The vocal folds treated with mitomycin-C showed fewer fibroblasts and less collagen within the superficial layer of the lamina propria than the control vocal folds (p < .05, Student's t-test, paired analysis). Inflammatory infiltrate was not significantly different between the two sides. Consistent with the known suppression of fibroblast proliferation by mitomycin-C, the treated vocal folds showed less connective tissue response to the surgical injury. In contrast to the reported positive effects of mitomycin-C on tracheal and glottic stenosis, the observed decrease in the healing response in the present study had negative consequences on the vocal fold vibratory pattern. PMID- 11201806 TI - Malignant carotid body tumors: report of three cases. AB - The aim of the current report was to describe 3 cases of malignant carotid body tumor (CBT) and to review the literature. My clinical records of 87 CBTs in 81 patients (6 bilateral) were reviewed, 79 of which were operated on. Three malignant cases were found. The first was in a 40-year-old man who presented with pulmonary metastases 6 years after resection of a CBT. He was treated with chemotherapy and interferon, but died with disseminated disease 2 years later. The second case was in a 56-year-old woman who had a 5-cm, fixed, hard mass in the upper aspect of the neck and a paralysis of the left vocal cord. This lesion was completely resected, and a shunt and reconstruction with a saphenous vein graft were performed. Pathology revealed a malignant chemodectoma with invasion to 2 of the 5 lymph nodes removed. Radiotherapy (50 Gy) was given after the operation. She is well and free of disease 68 months after the resection. The third case was in a 61-year-old woman who presented with an 8-cm nontender, hard, immobile mass in the left upper neck that displaced the left wall of the oropharynx toward the midline. A carotid arteriogram showed a CBT. On computed tomography, the tumor extended to the infratemporal fossa with no bone involvement. The lesion was embolized with a 40% reduction in vascularity. At surgical exploration, the tumor involved the sternocleidomastoid muscle and the lymph nodes at levels II and III, and the internal carotid artery could not be dissected free at the skull base, so only a partial resection was performed. This patient was lost to follow-up. These 3 cases are in agreement with the literature. Locoregional control is usually obtained with complete primary tumor resection and lymphadenectomy and eventual radiotherapy. Surgery with radiotherapy seems to be effective for isolated metastases. Current multidisciplinary treatments have been unsuccessful in controlling disseminated disease. PMID- 11201807 TI - Further experience with tracheojejunal shunt speech after pharyngolaryngoesophagectomy. AB - Over the past 10 years, 16 patients have undergone the tracheojejunal shunt operation for voice reconstruction after undergoing pharyngolaryngoesophagectomy with free jejunum reconstruction for advanced hypopharyngeal cancer. For the purpose of voice reconstruction, a 2-cm inferiorly based tracheal flap is obtained from the membranous part of the trachea by removing 4 cartilaginous tracheal rings. After the establishment of digestive continuity with the jejunal graft, a side-to-side anastomosis is created by approximating the incised margin of the jejunal mucosa to that of the tracheal flap. The tracheal flap is tubed to construct the tracheojejunal shunt. In addition, the incised margin of the jejunal serosa is sutured to the lateral wall of the shunt to reinforce the approximation of the shunt to the jejunal graft. Thirteen of the 16 patients (81%) were initially capable of voice production. The length of time during which tracheojejunal speech has been used ranges from 18 to 122 months, with a mean of 55 months. During follow-up, 12 of the 13 patients (92%) have been able to swallow without aspiration. PMID- 11201808 TI - Performance characteristics of fluorescence endoscope in detection of head and neck cancers. AB - Laser-induced fluorescence endoscopy (LIFE) is a noninvasive method for detecting early cancers in hollow organs. A laser-induced fluorescence endoscope that was designed for lung imaging was investigated for its effectiveness in comparison to white light endoscopy (WLE) in localizing head and neck cancers. A total of 196 images from 98 sites in 56 patients were graded into 5 levels from normal to definitely abnormal. A cutoff level to differentiate normal from abnormal images was chosen from a receiver operating characteristic curve. On this basis, LIFE (sensitivity, 92.86%; specificity, 78.57%) was observed to be more effective and reliable than WLE (sensitivity, 67.86%; specificity, 70%) in locating neoplastic foci and precancerous lesions. Nevertheless, WLE was helpful in presenting anatomic details. The reliability of LIFE varied from site to site. It excelled in examination of the oropharynx (sensitivity, 100%; specificity, 96.20%), but was less effective for lesions of the nasopharynx (sensitivity, 66.70%; specificity, 75.00%). In standardizing the test, interobserver variation was assessed, and good agreement in image interpretation was confirmed by statistical analysis. In conclusion, LIFE was found to be an effective and reliable tool for detecting head and neck cancers. PMID- 11201809 TI - Globosal basal cells are identified as proliferating cells in mouse olfactory epithelium. AB - Although anti-bromodeoxyuridine (BrdU) antibodies are used for detecting proliferating cells, they may stain proliferating cells in phases following the S phase, except for G1. Anti-Ki67 antibodies are widely used for detecting proliferating cells in all phases of the cell cycle (G1-, S-, G2-, and M-phase), but not in resting cells (G0-phase). Anti-cyclin D1 antibodies are used to detect proliferating cells in the G1-phase. The present study investigated the olfactory epithelium of mice by double immunostaining using antibodies to BrdU, Ki67. cyclin D1, and cytokeratin 14 (CK14). The cells positive to the anti-BrdU antibody, the anti-Ki67 antibody, and the anti-cyclin D1 antibody differed from the cells positive to the anti-CK14 antibody. Thus, we confirmed that the proliferating cells in all the phases of the cell cycle, including the G1-phase, were globosal basal cells, which were the precursors of the olfactory cells. PMID- 11201810 TI - Effects of transglottal pressure on fundamental frequency of phonation: study with a rubber model. AB - The fundamental frequency of phonation (F0) change per unit change in transglottal pressure (dF/dP) was studied at different extension lengths and masses of the vibrating part of a rubber model. The dF/dP was decreased when the vibrating part was extended, and also when the mass of the vibrating part was increased. In the former, the F0 was increased, and in the latter, the F0 was decreased. In humans, we have noticed that when the F0 was increased, the dF/dP first decreased and then increased, taking a V-shaped curve as a function of the F0. The present study reveals the mechanism underlying the V-shaped curve observed in humans. PMID- 11201811 TI - Endobronchial tumors in children: an uncommon clinical entity. AB - We performed a retrospective chart review of 10 children in whom endobronchial tumors were diagnosed in a tertiary-care children's medical center from 1988 to 1998. Of the 10 patients, 6 were male and 4 were female (8 white, 1 Hispanic, 1 African American). The mean age at presentation was 5.2 years. Eight tumors were benign, and 2 were malignant; 4 were on the right side, 3 were on the left side, and 3 were bilateral. Histologic findings included 3 bronchial papillomas, 3 inflammatory masses, 1 endobronchial hemangioma, 1 leiomyoma, 1 mucoepidermoid carcinoma, and 1 bronchial carcinoid. Endobronchial tumors in children are a rare disorder. The diagnosis requires a high index of suspicion in children with atypical or chronic respiratory complaints. Newer adjuvant medical therapies and surgical innovations offer improved disease control in these patients, and a multidisciplinary approach is often warranted. PMID- 11201812 TI - Local recurrences following transoral laser surgery for early glottic carcinoma: frequency, management, and outcome. AB - Although transoral laser surgery (TLS) for the treatment of early stage glottic carcinoma is now widely used, the patterns of local recurrences, related re treatment methods, and results have not been documented comprehensively. Two hundred fifty-two patients with glottic carcinoma stage I or II were treated for cure with TLS alone and followed up for 24 to 139 months (mean, 62 months). Their charts were retrospectively reviewed to identify local recurrence patterns. Thirty-five patients (13.9%) presented with local recurrences or second laryngeal primaries 4 to 84 months (mean, 23 months) after initial treatment. Of the 161 patients classified T1N0M0, 21 (13.0%) suffered local recurrences, and in the 91 classified T2N0M0, 14 (15.4%) tumors recurred. If tumors recurring more than 60 months after initial treatment are considered second primary tumors rather than recurrences, then only 18 (11.2%) of 161 patients classified T1N0M0 would have had a recurrence. However, the difference in local control between patients with stage I versus stage II disease would still not be significant (p = .41). Of the 35 patients with local recurrences, 16 (45%) were managed with total laryngectomy, 10 (28.6%) with further TLS, 4 (11.4%) with partial laryngectomy, and 2 (5.7%) with radiotherapy, and 3 (8.6%) had no curative treatment. Accordingly, 16 patients (45.7%) with local treatment failure could be treated with further organ-sparing treatment methods. The actuarial overall survival, disease-specific survival, and organ preservation rates 5 years after the diagnosis of recurrent disease were 43.6%, 74.6%, and 33.7%. Transoral laser surgery leads to local control rates that are comparable to those found after radiotherapy for lesions classified T1 and leads to slightly better control rates for lesions classified T2, but the results are inferior to those achieved with conventional partial laryngectomy. However, if local recurrence occurs, then more re-treatment options are available after TLS as compared to initial radiotherapy or open surgery. PMID- 11201813 TI - Congenital nasal pyriform aperture stenosis: diagnosis and management of 20 cases. AB - The objective of this study was to review the characteristics of congenital nasal pyriform aperture stenosis (CNPAS) in a series of 20 children seen between 1993 and 1996. The diagnosis was made by physical examination and computed tomography scan. A single central maxillary incisor was detected in 12 cases (60%). Three children had morphological abnormalities of the pituitary gland shown on magnetic resonance imaging. One child had an antidiuretic hormone deficiency, and another child had a growth hormone deficiency. Two children had craniosynostoses, 1 of which was Apert's syndrome. All patients underwent operation by a sublabial approach, and 1 was referred for a columellar necrosis after nasal stenting. After surgery, all patients showed improvement, and the nasal stenting was usually removed 1 week after surgery. Follow-up revealed normal breathing. In conclusion, CNPAS was previously considered to be an unusual cause of nasal obstruction in neonates and infants. The number of cases treated recently in our department suggests that this newly recognized entity is more common than expected. PMID- 11201814 TI - Immunohistochemical analysis of small cell carcinoma of the head and neck: a report of four patients and a review of sixteen patients in the literature with ectopic hormone production. AB - Small cell carcinoma (SCC) occurs mostly in the lung, and in some patients is accompanied by production of ectopic hormones. Small cell carcinoma of the head and neck is very rare. We report 4 patients with SCC of the head and neck (larynx, tonsil, maxillary sinus, and parotid gland). The patient with SCC of the maxillary sinus demonstrated a high level of plasma serotonin and overexpression of parathyroid hormone; however, he did not show any related symptoms. The patient with SCC of the tonsil showed the syndrome of inappropriate secretion of antidiuretic hormone associated with antidiuretic hormone hyperproduction at the terminal stage. In the literature, 16 patients with SCC of the head and neck with ectopic hormone production have been reported. Antidiuretic hormone and adrenocorticotropic hormone were the hormones that caused clinical symptoms (paraneoplastic syndromes). We believe that the evaluation of hormonal syndromes is valuable for diagnosis and treatment. PMID- 11201815 TI - Nitric oxide mediates platelet activating factor-induced microvascular leakage in rat airways. AB - Platelet activating factor (PAF), a highly potent chemical mediator in inflammation and allergic reactions, induces microvascular leakage in several tissues. In rat airways, PAF-induced microvascular leakage is probably mediated by an endothelial cell receptor in the microvessels. Nitric oxide (NO), first identified as endothelium-derived relaxing factor, has been suggested to be a mediator of airway microvascular leakage. However, the role of NO in PAF-induced microvascular leakage in the airways has not yet been established. The aim of this study was to investigate the role of NO in PAF-induced microvascular leakage in rat nasal mucosa and trachea. We injected PAF (1 microg/kg) intravenously, and the amount of PAF-induced microvascular leakage was measured with extravasation of Evans blue dye (30 mg/kg, injected intravenously 5 minutes before the injection of PAF) by means of spectrophotometry and fluorescence microscopy. Five Sprague-Dawley rats were pretreated with NG-nitro-L-arginine methyl ester (L NAME; 10 mg/kg, intravenously injected 1 hour before the injection of PAF) to inhibit NO synthase, and control rats (n = 4) were pretreated with normal saline solution. The average amount of extravasated Evans blue dye was significantly lower in the L-NAME-pretreated rats than in the control rats (t-test, p < .01). Tissue sections of the L-NAME-pretreated rats clearly showed a decreased extravasation of Evans blue dye on fluorescence microscopy. In conclusion, pretreatment with L-NAME clearly inhibited PAF-induced microvascular leakage in the nasal mucosa and trachea of rats. This finding implies that PAF may activate the constitutive endothelial NO synthase in the microvessels, and that activated endogenous NO may mediate PAF-induced microvascular leakage in rat airways. PMID- 11201816 TI - Microbiology of serous otitis media in children: correlation with age and length of effusion. AB - The purpose of this study was to correlate the microbiology of serous otitis media in children with the duration of the condition and the patient's age. Aspirates of serous ear fluids from 114 children were examined for aerobic and anaerobic bacteria. Bacterial growth was noted in 47 patients (41%). Aerobic organisms only were recovered in 27 aspirates (57% of the culture-positive aspirates); anaerobic bacteria only in 7 (15%); and mixed aerobic and anaerobic bacteria in 13 (28%). A total of 83 bacterial isolates were recovered, accounting for 1.8 isolates per specimen (1.2 aerobes and 0.6 anaerobe). There were a total of 57 aerobic isolates, including Haemophilus influenzae (15 isolates), Streptococcus pneumoniae (13), and Staphylococcus sp (12). Twenty-six anaerobes were recovered, including anaerobic gram-positive cocci (10), Prevotella spp (8), and Propionibacterium acnes (4). The rate of positive cultures (20 of 36; 56%) was higher in patients younger than 2 years of age than in those older than 2 years of age (27 of 78; 35%). Streptococcus pneumoniae and H influenzae were more often isolated in children younger than 2 years of age and those with effusion for 3 to 5 months, whereas anaerobes were recovered more often in those older than 2 years of age and those with effusion for 6 to 13 months. These data illustrate the effects of the length of effusion and age on the recovery of aerobic and anaerobic bacteria in serous otitis media. PMID- 11201817 TI - Volumetric and dimensional analysis of the guinea pig inner ear. AB - The objective of this study was to provide accurate volumetric data on the fluid spaces and soft tissue in the guinea pig inner ear by measuring all histologic serial sections by means of Metamorph Imaging Software at 400x to 1,000x magnification. The total endolymph volume of the inner ear was 4.691 mm3, of which 1.501 mm3 was in the cochlea, 3.090 mm3 in the vestibular labyrinth, and 0.100 mm3 in the endolymphatic duct and sac. The total perilymph volume was 15.938 mm3, of which 8.867 mm3 was in the cochlea and 7.071 mm3 in the vestibular labyrinth. The volume of the organ of Corti per millimeter length increased toward the apex, but the volumes of the stria vascularis, spiral ligament, and spiral limbus decreased. The volume of the macula utriculi was larger than that of the macula sacculi. The measurement of the luminal surface area of the stria vascularis was 3.944 mm2, and that of the vestibular dark cells was 5.772 mm2. PMID- 11201818 TI - Ectopic growth hormone-secreting pituitary adenoma in the sphenoid sinus. PMID- 11201819 TI - [Ischemic heart disease and metabolic syndrome X (family study)]. AB - AIM: To evaluate prevalence of metabolic syndrome "X" (MS) components in the families of probands and their wives regarding the presence of hyperinsulinemia and in probands' children of both sexes regarding their having vegetovascular dystonia. MATERIAL AND METHODS: 92 families were selected by the proband who survived acute myocardial infarction (MI) at the age under 50: 92 probands (mean age 47 +/- 1.1 years), 57 probands' wives (mean age 47 +/- 0.7 years), 20 sons (mean age 18.3 +/- 0.8 years), 24 daughters (mean age 19.1 +/- 1.0 years). Two groups were formed: group 1 of 48 probands and 25 wives (the presence of hyperinsulinemia in the proband); group 2 of 44 probands and 32 their wives (controls with normal insulin levels). Anthropometric, arterial pressure and lipid-hormonal measurements were made by standard techniques. Nutrition was studied by random reproduction of 24-h diet. RESULTS: More factors of risk to develop atherosclerosis and MS"X" components in probands and their wives were found in group 1. More frequent in the parents were the following MS components: hypoalphacholesterolemia, overweight, arterial hypertension, hyperapolipoprotein B-emia. Vegetovascular asthenia in the probands' children predisposed to cardiovascular diseases is closely linked with the presence of hypoalphacholesterolemia, hypertriglyceridemia, overweight and arterial hypertension. CONCLUSION: MS "X" for probands and their wives is a "malignant" risk factor for cardiovascular diseases; in the presence of IHD in father, vegetovascular asthenia in children is a risk factor of cardiovascular disease. PMID- 11201820 TI - [Dynamics of changes in levels of insulin, glucagon, and C-peptide during glucose tolerance test in patients with coronary atherosclerosis]. AB - AIM: To study velocity characteristics of changes in the levels of insulin, glucagon and C-peptide in the course of the intravenous glucose tolerance test (IGTT). MATERIAL AND METHODS: Glucose, insulin, glucagon and peptide levels were measured in the course of IGTT performed in 50 patients with coronary atherosclerosis (CA) who survived transmural myocardial infarction, 32 individuals with hereditary predisposition to CA and 30 controls free of cardiovascular or endocrine pathology. The results were approximated using high degree polynomes allowing calculation of the first and second derivatives (the velocity and rate of its change). RESULTS: CA patients showed inhibited changes of blood glucose, immunoreactive insulin. The reduction of the latter lasted longer than that in the control group. CONCLUSION: Under urgent mobilization of blood glucose regulation system, CA patients develop retention of immunoreactive insulin. PMID- 11201821 TI - [Myocardial infarction in patients with non-insulin-dependent diabetes mellitus and dependence of the quality of life on the individual psychological type]. AB - AIM: To examine clinical features, complications, short- and long-term outcomes of myocardial infarction (MI) as well as quality of life (QL) in patients with non-insulin-dependent diabetes mellitus (NIDDM), to analyze relations between the above parameters and psychologic personal traits of the patients. MATERIAL AND METHODS: The study entered 240 NIDDM patients with MI (the test group) and 260 control nondiabetic MI patients. The examination was made using standard techniques and AMPI. RESULTS: An anginal variant of initial MI in NIDDM patients was registered significantly less frequently than in the controls (76.7 vs 88.2%). The asthmatic variant occurred in 16.3 and 4.6% of the cases, respectively. In MI, NIDDM patients developed preinfarction and postinfarction angina pectoris less often than control patients (20 and 12.1% vs 71.9 and 25.7%, respectively). Mean psychological profile was high by AMPI scales 1, 2 and 6 in NIDDM patients, by scales 1, 3 and 8 in control patients. CONCLUSION: Pain syndrome in anginal initial MI in NIDDM patients is less pronounced and becomes weaker with growing duration of diabetes. Concomitant diabetes mellitus has an insignificant influence on deterioration of quality of life in the postinfarction period. PMID- 11201822 TI - [Thrombolytic therapy of myocardial infarction in a patient with the transplanted heart (case report)]. PMID- 11201823 TI - [Long-term study of the prevalence of arterial hypertension and outcomes of multifactorial prophylaxis in organized groups of employees]. AB - AIM: To evaluate trends in arterial hypertension (AH) and other risk factors and their changes after active prevention program. MATERIAL AND METHODS: 1382 male and 1555 female volunteers were included into the group of active prevention at the workplace vs 1024 male and 776 female controls. 5-year follow-up covered 543 males and 569 females from the prevention group against 97 male and 119 female controls. 10-year follow-up covered 82 males and 191 females, 178 males and 118 females, respectively. RESULTS: Risk factor correction produced a significant decrease in both systolic and diastolic BP levels, prevalence of ECG deteriorations, smoking habits occurrence, overweight. Overall mortality rate, CHD and stroke mortality were significantly less frequent in the prevention group. This group had also less days of temporary disability. CONCLUSION: The primary and secondary "in office" prevention for 5 to 10 years diminishes prevalence of risk factors. The temporary disability rate depends on the presence of arterial hypertension. The latter together with the other main risk facts significantly influences cardiovascular and general mortality rates. PMID- 11201825 TI - [Complete atrioventricular block without syncopal conditions. Implantation of the pacemaker or observation? (case report)]. PMID- 11201824 TI - [Effects of manual therapy on pain reflex syndromes and various hemocoagulation parameters in patients with ischemic heart disease after surgical treatment]. AB - AIM: To evaluate effects of manual therapy on clinical manifestations, hemocoagulation in CHD patients early after surgery. MATERIAL AND METHODS: Microcirculation, blood rheology, platelet count and aggregation by Born, plasma recalcification time according to Bergergof and Roka, plasma tolerance to heparin according to Gormsen, fibrinogen content by Bidwell in Andreenko's modification, the condition of vertebromotor segments were assessed in 68 CHD patients early after coronary artery bypass surgery (CABS). RESULTS: The addition of manual therapy to the complex of early rehabilitation measures in coronary patients early after CABS eliminates postoperative anginal attacks in 70% cases, reestablishes balance of cellular and plasma components of hemostasis, enhances fibrinolytic activity. CONCLUSION: The addition of manual therapy in the rehabilitation complex is recommended early after CABS. PMID- 11201826 TI - [Hydrogen peroxide--a marker for respiratory tract inflammation in patients with bronchial asthma]. AB - AIM: To test H2O2 as a marker of respiratory tract inflammation in patients with bronchial asthma (BA). MATERIAL AND METHODS: The study entered 70 patients (20 males and 50 females) with atopic asthma (AA) aged 18 to 62 years (mean age 32.6 years). H2O2 concentration in the expired air (CEA) was determined spectrophotometrically (Gallati & Pracht, 1985), content of eosinophilic cationic protein (ECP) in blood--with radioimmunoassay kits (Pharmacia & Upjohn, Sweden). Forced expiratory volume per 1 second (FEV1) was used for assessment of severity of bronchial obstruction. Bronchial hyperreactivity was studied by means of the histamine bronchoprovocative test. RESULTS: H2O2 in CEA in BA patients was higher than in healthy subjects (0.127 +/- 0.010 microm/l vs 0.024 +/- 0.004 microm/l). H2O2 concentration significantly correlates with FEV1 (r = -0.449; p < 0.001), bronchial hyperreactivity to histamine (rs = -0.382; p < 0.05) and ECP in blood plasma(r = 0.625; p < 0.01). CONCLUSION: It was proved possible to use H2O2 in CEA for evaluation of respiratory inflammation in BA patients. PMID- 11201827 TI - [Immune status of patients with chronic bronchitis and neurocirculatory asthenia]. AB - AIM: To study changes in immune system of patients with various forms of chronic bronchitis (CB) and neurocirculatory asthenia (NCA). MATERIAL AND METHODS: Neurological and immunological examinations were made in 84 patients with CB exacerbation and 51 control subjects. RESULTS: It was found that 60% of CB patients had NCA. No negative effects of NCA on immune system in CB patients were registered. Suppression of immune system and secondary immunodeficiency occurred more frequently in CB patients without signs of NCA. 40% of CB patients had vagotonic NCA in which immunological disorders manifested most clearly. CONCLUSION: Vegetative disorders in CB patients do not affect immunological system. Functional testing of autonomic nervous system is suggested for prediction of immune system condition. PMID- 11201828 TI - [Acid-base balance parameters of the synovial fluid in patients with early-stage rheumatoid arthritis]. AB - AIM: To study changes in acid-base balance (ABB) of synovial fluid (SF) in rheumatoid arthritis (RA) patients in respect of the disease duration, clinical symptoms and treatment. MATERIAL AND METHODS: The examination of verified RA patients included clinical, x-ray, immunological and special tests. The patients received nonsteroid antiinflammatory drugs, 2 weeks later--physiotherapy followed by 10-day basic treatment (tauredon, methotrexate or cyclophosphamide). RESULTS: Before the treatment, SF acidotic shift was found in all the patients. The shift correlated with activity of the inflammation, serologic affiliation to the rheumatoid factor, presence of systemic manifestations, x-ray signs of the articular changes in response to the treatment. Attenuation of the inflammatory process accompanies an increase in SF acidotic shift. In administration of methotrexate SF pH was higher than in the use of other drugs. CONCLUSION: Adjuvant ABB correctors are recommended for RA patients. PMID- 11201829 TI - [Quality of life in rheumatoid arthritis patients]. AB - AIM: To study quality of life (QL) in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: Questionnaire survey (MCA, BIPQ, AIMS, MHAQ) covered 190 RA patients (mean age 47.7 +/- 1.4 years). Many of them were group II invalids. All the patients had slow-progressive polyarthritis, articular and seronegative RA prevailed. Most of the patients had articular and seronegative RA with first degree activity, x-ray stage II and third-degree deficiency of the articular function. RESULTS: It is shown that RA patients have subnormal quality of life. Its deterioration was related to clinical parameters: duration of the disease and its activity, invalidity, X-ray stage, articular and locomotor functions, psychological status. Hypochondriac, apathical and neurastenic reactions to the disease occurred most frequently. Euphoric reaction to the disease was a positive factor for QL. Changes in social status were essential for QL in RA patients. CONCLUSION: QL is an integral indicator of health status in RA patients. It can be estimated basing on only one questionnaire--AIMS as it includes all the necessary components. PMID- 11201830 TI - [Anxiety disorders as psychological personality characteristics in patients with rheumatoid arthritis]. AB - AIM: To study types of anxious disorders (AD) in patients with rheumatoid arthritis (RA) and AD correlations with clinicolaboratory indices. MATERIAL AND METHODS: 80 RA patients and 38 healthy subjects have undergone MMPI test. RESULTS: 95% of the examinees were found to have AD which seem to form in active participation of psychoemotional factors. Development of AD was characterised by internal strain, emotional stress, anxiodepressive conditions. Psychological profiles of AD patients were analysed. No correlations were found with clinicolaboratory indices: Additional correlations exist between the MMPI scales in AD. CONCLUSION: AD in RA patients may result in vegetative dysfunctions. PMID- 11201832 TI - [Antithrombogenic activity of the vascular wall, hemostasis, and rheological characteristics of blood in patients with unstable angina pectoris and various types of hyperlipoproteinemia]. AB - AIM: To examine antithrombogenic activity of the vascular wall, some hemostatic and rheological properties of blood in patients with unstable angina (UA) and various types of hyperlipoproteinemia (HLP). MATERIAL AND METHODS: 102 UA patients were divided into groups by HLP types according to D. S. Frideriksen. Antithrombogenic properties of blood vessel wall were examined with the cuff test, blood rheology--with AKP-2 analyser, hemostasis and lipid metabolism--with standard test. RESULTS: UA patients with HLP have low antithrombogenic activity of vascular wall. The most noticeable shifts to hypercoagulation were found in patients with HLP types 2a and 2b. Blood rheology was abnormal (high red cell aggregation in low deformability) in patients with HLP types 2a, 2b and 4. CONCLUSION: Patients with UA demonstrate relationships between antithrombogenic activity of vascular wall, intensity of lipid metabolism, hemostasis and blood rheology. PMID- 11201831 TI - [Characteristics of cardiac and nervous system impairment in patients with systemic lupus erythematosus from regions with various levels of environmental pollution]. AB - AIM: To characterize clinical features of systemic lupus erythematosus (SLE) in persons living under various environmental pollution. MATERIAL AND METHOD: Three groups of SLE patients living in the Orenburg region were examined: those exposed to intensive production pollution (n = 35 patients), exposed to mild pollution (n = 15), unexposed to production pollution (n = 25 patients). The pollution intensity was assessed by total aerogenic, water and soil pollution rates. RESULTS: The hair from 69 patients contained 24 chemical elements. More severe clinical symptoms of SLE were registered in patients living in conditions of intensive production pollution. These symptoms' severity directly correlated with the level of heavy metals in the hair of SLE patients and inversely correlated with hair levels of essential chemical elements. CONCLUSION: Chemical pollutants directly impair organs and tissues of SLE patients and indirectly do this via damaged immune system. PMID- 11201833 TI - [Angiotensin converting enzyme-angiotensin II system, atherosclerosis, and angiotensin-converting enzyme inhibitors]. PMID- 11201834 TI - [Outpatient bioresonance treatment of gonarthrosis]. AB - AIM: Comparative effectiveness of gonarthrosis treatment with standard methods alone and in combination with bioresonance. MATERIAL AND METHODS: The trial entered 75 patients with verified osteoarthrosis of the knee joints (stage I-III by Y. Kellgren). They were divided into two groups. 40 patients of group I received standard combined therapy with nonsteroid antiinflammatory drugs, reducers of trophic processes, physiotherapy. 35 patients of group 2 received the above standard therapy plus bioresonance treatment (BRT). The treatment course in both the groups took 5-6 weeks. There were no statistical differences between the groups in age, sex, duration and severity of the disease. The response was assessed by changes in clinical and laboratory, arthrological and arthrosonographic parameters before the treatment and 3, 5-6 weeks, 12 months after it. RESULTS: The response to treatment was significantly higher in group II (57.5 against 94%). Symptoms of synovitis and tendenitis relieved more also in group 2 (32.5 against 75%). Group 2 patients retained mild pain at rest for a year, while in group I pains intensified by month 6 after the treatment. CONCLUSION: The addition of BRT to standard therapy of gonarthrosis potentiates anesthetic, antiinflammatory and antiexudative effects; prolongs therapeutic action. BRT was well tolerated. Side effects were absent. PMID- 11201836 TI - [Filgrastim therapy in acute nonlymphoblastic leukemia]. AB - AIM: To specify effects of the granulocytic colony-stimulating factor (G-CSF) in the treatment of acute nonlymphoblastic leukemia. MATERIAL AND METHODS: Thirteen patients with acute myeloid leukemia (AML) were treated in the Hematological Clinic of the Higher Medical Institute in Plovdiv in 1996-1998. All of them received a standard induction therapy with cytosin arabinoside + daunorubicin (7 + 3 days). During the first neutropenic phase (neutrophils < 0.5 x 10(9)/l) G-CSF filgrastim was applied (5 microg/kg/day, s.c.) until a recovery of the neutrophil count reached > 1.0 x 10(9)/l and was maintained for 3 successive days. The control group consisting of patients matched by age, gender, an AML cytomorphologic variant was given the same therapy but filgrastim. RESULTS: The study group showed quicker recovery of the neutrophil count (12.6 vs 16.8 days), reduced febrile period (9.8 vs 12.4 days) and shorter duration of parenteral antibiotic treatment (9.8 vs 12.4 days) compared to controls. No statistically significant difference between both groups was found in the duration of the antimycotic treatment (p > 0.05). No cytological signs of aggravation of basic disease were absent in patients who received filgrastim. CONCLUSION: Administration of G-CSF in AML is useful as it promotes rapid overcoming of neutropenia and its complications. PMID- 11201835 TI - [Immunogenetic markers in hemoblastosis]. AB - AIM: To establish for hemoblastoses general and individual associations between HLA genes and predisposition or resistance to malignant transformation of hemopoiesis. MATERIAL AND METHODS: Antigens of class I and class II genes were determined by microlymphocytotoxic test and DNA typing (PCR-SSP) in 30 patients with acute myeloblastic leukemia (AML), 47 patients with acute lymphoblastic leukemia (ALL), 52 patients with chronic myeloblastic leukemia (CML), 58 patients with lymphogranulomatosis (LGM) and 224 donors. RESULTS: HLA specificities were elucidated frequency of which was high in all the above nosological entities: Cw7 (RR 2.5 to 5.22), DRB1*11 (RR 2.3 to 4.88). Frequency of antigen B5 was high in three diseases (RR 2.14-2.6). A number of specificities have distribution deviations typical for only one or two diseases (A19--AML and CML, B27--ALL, DRB1*08--AML). The HLA-gene was detected the frequency of which was low in three diseases--DRB1*07 (RR 0.39 to 0.11). Individual preventive HLA genes for AML, ALL, LGM were A2, B8; A1, B8, B40; DRB1*01, respectively. CONCLUSION: Cw7, DRB1*11, B5 are HLA-specificities marking hemopoiesis predisposition to malignant transformation in general. Development into a certain nosological entity depends on combination of general HLA-genes with markers of individual hemoblastosis. DRB1*07 is a general preventive gene. Preventive HLA genes can be also individual for the above hematological diseases. PMID- 11201837 TI - [Cardiac pathology in idiopathic hypereosinophilic syndrome]. PMID- 11201839 TI - [Atopy and atopic and pseudoatopic diseases. II. The role of constitution type]. PMID- 11201838 TI - [Effect of enalapril on clinical and metabolic characteristics in patients with non-insulin-dependent diabetes and arterial hypertension]. PMID- 11201841 TI - [Results of the multicenter controlled study of the hypolipidemic drug polycosanol in Russia]. AB - AIM: To compare efficacy and tolerance of polycosanol vs besafibrate in patients with hypercholesterolemia (HCE). MATERIAL AND METHODS: A multicenter controlled double blind randomised trial entered 113 patients with HCE. After 5 weeks of diet the patients were randomised into two groups. 59 patients of group 1 received polycosanol (10 mg/day), 54 patients of group 2 were given besafibrate (400 mg/day) for 8 weeks. RESULTS: The 8-week course of treatment was completed by 103 patients (91%): 57(97%) patients of group 1 and 46(85%) patients of group 2. In group 1 total cholesterol diminished by an average of 15%, LDLP cholesterol fell by 18%, triglycerides by 15%, while in group 2 a respective decrease was 8, 11 and 6%. Side effects in group 1 were mild. CONCLUSION: A hypolipidemic effect of polycosanol in a daily dose 10 mg is superior to that of besafibrate in a daily dose 400 mg. PMID- 11201840 TI - [Prospects for pharmacological effects on renin-angiotensin and sympathetic nervous systems in patients with arterial hypertension]. PMID- 11201842 TI - [Informed consent of the patient to examination and treatment (a foreign literature review)]. PMID- 11201843 TI - [Carotid sinus syndrome and vasovagal syncope]. PMID- 11201844 TI - [The role of beta2-agonists in treatment of severe acute asthma]. PMID- 11201845 TI - Another thyroid emergency. PMID- 11201846 TI - Thyroid hormone regulation of apoptosis induced by retinoic acid in promyeloleukemic HL-60 cells: studies with retinoic acid receptor-specific and retinoid x receptor-specific ligands. AB - 3,5,3'-Triiodo-L-thyronine (T3) potentiates apoptosis during the all-trans retinoic acid-induced differentiation of promyeloleukemic HL-60 cells. We examined whether the retinoid receptor-specific thyroid hormone action is present during differentiation of HL-60 cells in this study. We used two distinct retinoid receptor agonists. T3 potentiates G1 arrest induced by Am80, a retinoic acid receptor (RAR)-specific agonist, but had no effect on G1 arrest induced by HX600, a retinoid x receptor (RXR)-specific agonist. Am80 alone induces the apoptosis, and T3 enhances it. Although HX600 alone fails to increase the apoptotic fraction, T3 enables the compounds to induce apoptosis. Am80-induced expression of CD11b, a marker for the differentiation, is enhanced by T3. However, T3 or HX600 or both do not affect the expression of CD11b. T3 does not alter the amount of mRNAs of various members of the bcl-2 family. T3, however, enhances the Am80-induced expression of bfl-1 and suppression of bcl-2. In contrast, T3 does not alter either bfl-1 and bcl-2 expression in the presence of HX600. Our observations suggest that cooperative action of T3 with an RXR specific ligand is different from that with an RAR ligand in cellular apoptotic regulation and that thyroid hormone may be available as a chemotherapeutic agent in acute leukemia. PMID- 11201847 TI - Novel TSHR germline mutation (Met463Val) masquerading as Graves' disease in a large Welsh kindred with hyperthyroidism. AB - Hereditary nonautoimmune hyperthyroidism is caused by activating germline mutations in the thyrotropin (TSH) receptor (TSHR) gene. We describe an extended Welsh kindred with toxic thyroid hyperplasia affecting 8 family members in three generations and a history consistent with thyrotoxicosis in a further three generations now deceased. A novel heterozygous germline mutation (ATG --> GTG; Met463Val) was identified in the second membrane spanning TSHR region in 6 relatives with thyrotoxicosis and goiter and absence of TSHR antibodies. Screening of 5 additional family members led to the identification of 2 siblings with the mutation, who were asymptomatic at the time, although subsequent thyroid function tests in these children showed suppressed serum TSH and increased serum free triiodothyronine (FT3) and free thyroxine (FT4) concentrations. Functional studies of the novel TSHR germline mutation demonstrated a constitutive activation of the cAMP pathway, which in the thyroid controls both thyroid hormone production and stimulation of thyroid growth. The molecular diagnosis in this family has clinical implications: genetic counseling is required, and primary thyroid ablation should be advocated as the preferred treatment in the patients with the constitutively activating TSHR germline mutation. PMID- 11201848 TI - Carnitine is a naturally occurring inhibitor of thyroid hormone nuclear uptake. AB - Carnitine (3-hydroxy-4N-trimethylammoniumbutanoate) is a naturally occurring quaternary amine that is ubiquitous in mammalian tissues (concentrations in the order of mM). Based on limited studies of approximately 40 years ago, carnitine was considered to be a peripheral antagonist of thyroid hormone (TH) action. These interesting observations have not been explored. To study the biologic basis of this effect, we tested the following possibilities in three TH responsive cell lines: (1) inhibition of TH entry into cells; (2) inhibition of TH entry into the nucleus; (3) inhibition of TH interaction with the isolated nuclei; and (4) facilitated efflux of TH from cells. On a preliminary basis we had verified that these cell lines (human skin fibroblasts, human hepatoma cells HepG2, and mouse neuroblastoma cells NB 41A3) take up 14Ccarnitine; however, there was no 14Ccarnitine uptake into the nuclei. Concentrations of unlabeled carnitine as high as 100 mM did not affect (125I)T3 binding to isolated nuclei or exit of TH from cells, thus excluding possibilities numbered 3 and 4. At 10 mM camitine, (125I)T3 and (125I)T4 whole-cell uptake was inhibited by approximately 20% in fibroblasts and in HepG2, but by approximately 5% in NB 41A3 cells. Inhibition of T3 nuclear uptake was evaluated in HepG2 and NB 41A3 cells. At 10 mM carnitine, inhibition of T3 nuclear uptake was disproportionately higher, namely approximately 25% in neurons and 35% in hepatocytes. At 50 mM carnitine, there was a minimal additional decrease in whole-cell uptake of either hormone but a marked decrease in T3 nuclear uptake. The latter inhibition was approximately 60% in neurons and 70% in hepatocytes. We are aware of no inhibitor of TH uptake that has such a markedly different effect on the nuclear versus whole-cell uptake. Our data are consistent with carnitine being a peripheral antagonist of TH action, and they indicate a site of inhibition at or before the nuclear envelope. PMID- 11201849 TI - Epitope analysis of the human thyrotropin (TSH) receptor using monoclonal antibodies. AB - A panel of thyrotropin (TSH) receptor (TSHR) monoclonal antibodies (mAbs), produced using highly purified Chinese hamster ovary (CHO) cell-produced TSHR, has been used to study TSHR structure. All 41 mAbs recognized full-length TSHR containing complex carbohydrate (120 kDa), and 40 mAbs recognized full-length precursor-containing high mannose sugars (100 kDa). The mAbs also recognized TSHR cleavage products with three types of reactivity: type 1 mAbs reacting with bands at 70 kDa and 58 kDa, type 2 with bands at 70 kDa and 52 kDa, and type 3 with bands at 52 kDa and 40 kDa. Deglycosylation studies showed that the 70-kDa and 58 kDa bands contained complex carbohydrate, whereas the 52-kDa and 40-kDa bands were unglycosylated. These results are consistent with TSHR cleavage occurring at two sites. Cleavage at both sites gives rise to glycosylated A subunit (58 kDa) corresponding to the extracellular domain of the receptor and nonglycosylated B subunit (40 kDa) corresponding to the C-terminal transmembrane domain. Cleavage only at site 1 gives rise to the 58-kDa A subunit and a large B subunit (52 kDa). Cleavage only at site 2 gives rise to a large A subunit (70 kDa) and the B subunit (40 kDa). Four of the mAbs inhibited 125I-labeled TSH binding to solubilized full-length TSHR. TSH binding was inhibited by (a) two type 3 mAbs reactive with the N-terminal region of the B subunit (epitopes between amino acids 381 and 385 and between 380 and 418, respectively) and (b) two type 2 mAbs reactive with epitopes on the A subunit (between amino acids 246 and 260). These results together with previous studies on the direct binding of TSH to the TSHR A subunit suggest that at least two distinct regions of the TSHR sequence, including one region on the A subunit and one region on the B subunit, fold together to form part of a complex TSH binding site. PMID- 11201850 TI - Matrix metalloproteinases and the thyroid. AB - Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade components of the extracellular matrix (ECM) and basement membrane. They play a critical role in many physiological and pathological processes, such as tumor metastasis. The original concept-that MMP activity during metastasis is restricted solely to invasion of the basement membrane and destruction of ECM components-has been modified to encompass multiple aspects of tumor progression: tumor establishment, growth, angiogenesis, intravasation, extravasation, and almost all metastatic steps. Moreover, the role of tissue inhibitors of matrix metalloproteinases (TIMPs), originally believed to exhibit anti-invasion properties solely by virtue of their inhibition of MMPs, has been extended to include their multiple biological effects, such as growth promotion. In thyroid neoplasia as well, MMPs, in particular MMP-2, seem to be associated with metastatic potential. It would seem that similar and divergent patterns regulate MMP and TIMP gene expression in benign and malignant human thyrocytes, in many instances in agreement with the concept of MMPs playing the role of stimulating, and TIMPs inhibiting cell invasion. PMID- 11201851 TI - Graves' disease by any other name? PMID- 11201852 TI - Disseminated thyroid autonomy or Graves' disease: reevaluation by a second generation TSH receptor antibody assay. AB - The clinical diagnosis of disseminated autonomy (DISA) can only be established by exclusion of Graves' disease (GD). Both hyperthyroid conditions share the same scintigraphic appearance and can only be distinguished from each other clinically either by the presence or absence of endocrine ophthalmopathy (EO) or thyrotropin (TSH) binding inhibiting immunoglobulins (TBIIs). The purpose of this study was the reevaluation of thyroid autonomies originally classified as DISAs by a second generation radioreceptor antibody assay (RAA) (DYNOtest TRAKhuman) (B.R.A.H.M.S. Diagnostika, Berlin, Germany). The analysis included 32 patients (female: n = 25, male: n = 7; mean age: 46 +/- 18 years) who were initially diagnosed with DISA. All patients were TSH receptor (TSHR) antibody (TRAb) negative by a conventional radioimmunoassay (RIA) (TSH-REZAK RIA) (Medipan Diagnostica, Selchow, Germany) during their first evaluation. The presence of EO was excluded by clinical signs in all patients. Surgery had been performed prior to our evaluation in 5 patients and after our survey in 1 patient. Four patients had been treated previously with 131I. Ten patients were treated with thionamides during our evaluation, and 13 had not been treated before. One hundred three patients who had either healthy thyroids, nontoxic goiters, or focal autonomies served as controls and were evaluated both by the TSH-REZAK assay and the DYNOtest TRAKhuman assay. Seven of thirty-two (22%) patients originally classified as DISA were TRAb positive in the second-generation assay. In this group, 5 of 7 patients had a total thyroid volume (TTV) <30 mL (positive predictive value [PPW] for TRAb positivity 71%), and 5 of 7 patients had a diffuse goiter (PPW for TRAb-positivity 71%). Six of seven patients were anti-thyroperoxidase (TPO) positive (PPW for TRAb positivity 85%). A hypoechoid pattern on ultrasound was present by visual analysis in 3 of 7 patients (PPW for TRAb positivity 43%). A 100% PPW for TRAb positivity could be obtained if a goiter <30 ml was combined with anti-TPO positivity, but this combination was present in only 4 of 7 (57%) patients. With the second-generation assay, one false positive test result was observed in the control group. Surgery was performed in 6 patients who were TRAb negative in both assays. In all these cases, the histologic findings were compatible with autonomous transformation of the thyroid. Our study demonstrates that a significant number (22%) of patients formerly classified as DISA may actually have GD. However, DISA still exists as a clinical entity, and its pathophysiological link to multifocal and unifocal autonomy should be further investigated. PMID- 11201853 TI - Postintervention serum TSH levels may be useful to differentiate patients who should undergo levothyroxine suppressive therapy after thyroid surgery for multinodular goiter in a region with moderate iodine deficiency. AB - Recent studies have raised doubts about the efficacy of the postoperative use of levothyroxine (LT4) suppressive doses in patients who underwent thyroid surgery for multinodular goiter. The purpose of this retrospective study was to examine the efficacy of different doses of LT4 in preventing postsurgical recurrences of simple multinodular goiter and to identify a marker that could be useful in discriminating patients with a higher risk of developing recurrence. Two hundred thirty-two patients (57 male, 175 female) operated for nontoxic multinodular goiter were divided into two groups: (I) patients with normal postsurgery thyrotropin (TSH) levels (0.25 to 4.5 mU/L) and (II) patients with elevated postsurgery TSH levels (>4.5 mU/L). All patients were subjected to replacement (1.3 microg LT4/kg/day) or suppressive (1.7 microg LT4/kg/day) doses of LT4, and they were followed for a median period of 6 years (range 2 to 12). No statistical difference was found for sex, age, and postsurgery serum TSH between patients submitted to suppressive and replacement therapy. The ultrasound (US) detection of new postsurgery nodules of at least 0.5 cm maximum diameter was considered a recurrence of disease and was found in 10% of the cases studied. Patients with normal postsurgery serum TSH showed a high recurrence rate (30.4%) when submitted to lower daily doses of LT4. In patients with elevated postsurgery serum TSH, the rate of nodular goiter recurrence did not vary with different types of LT4 therapy. In conclusion, our results suggest that the postsurgical serum TSH is useful for prediction of nodular goiter recurrence, as it reflects the amount of residual functioning thyroid tissue in the cervical area. It may also be indicative of patients who might benefit from LT4 suppressive therapy. PMID- 11201854 TI - Surgical and pathological changes after percutaneous ethanol injection therapy of thyroid nodules. AB - Few data exist on the operative and pathological findings in patients having undergone previous percutaneous ethanol injection (PEI) therapy of thyroid nodules. We report here our experience with 13 patients operated on by the same surgical team. Two pathologists, both blinded to the previous PEI treatment, carried out histological evaluation. Reasons for surgery included PEI failure, suspicion of malignancy, and tracheal compression. The operations did not pose any special problem from the technical point of view, and the postoperative courses were uneventful. One patient who had a second operation developed hypoparathyroidism, and laryngeal nerve palsy was never observed. The histological diagnosis was hyperplastic or adenomatous nodule in 12 cases and papillary thyroid cancer in 1. No difficulty was found in evaluating the nodule capsule and surrounding vessels. In two lesions, nuclear enlargement and clearing were identified in thyroid follicles immediately adjacent to necrotic or scarred areas. These changes were considered reactive. In conclusion, patients previously treated by PEI were operated on without special technical problems. Histological diagnosis was not hindered, and there was no difficulty in ruling out malignant lesions. PEI, however, should be performed only by skilled operators, and incidental ethanol seepage throughout the nodule capsule must be carefully avoided. PMID- 11201855 TI - Graves' ophthalmopathy in the absence of elevated free thyroxine and triiodothyronine levels: prevalence, natural history, and thyrotropin receptor antibody levels. AB - The aims of this study were to (a) determine the prevalence of patients without elevated thyroid hormone levels in Graves' ophthalmopathy (GO) using current generation free thyroid hormone assays, (b) measure the prevalence of thyrotropin receptor antibodies (TRAb) in these cases, and (c) identify possible predictors of hyperthyroidism. Over a 30-month period, 1020 cases of thyroid eye disease were evaluated, of which only 19 (1.9%) met the diagnostic criteria. Ten (1%) had subclinical thyrotoxicosis, 7 (0.7%) were euthyroid, and 2 (0.2%) were hypothyroid as determined by a third-generation thyrotropin (TSH) assay. TRAb levels were measured in 16 of these 19 patients. The prevalence of TRAb varied according to the assay used. Polyethylene glycol-extracted thyroid-stimulating immunoglobulin (PEG-TSI), unfractionated thyroid-stimulating immunoglobulin (uTSI), first-generation porcine TSH-binding inhibitory immunoglobulin (pTBII), and second-generation human TSH-binding inhibitory immunoglobulin (hTBII) assays were positive in 93.8%, 50%, 18.8%, and 81.3% of patients, respectively. TRAb was detected by at least one method in all patients. Patients were followed up for 15 to 45 months. Hyperthyroidism developed in 4 patients (25%). Suppressed TSH levels and elevated TBII were predictors of hyperthyroidism. When sensitive assays are used, the prevalence of GO patients without elevated thyroid hormone levels is extremely low. The sensitivities of assays for TRAb detection differ substantially in these cases. PEG extraction improves the detection rate of TSI (p = 0.02), and hTBII assays improve the detection of TBII in these patients (p = 0.002). The high prevalence of TRAb in such cases supports a role for these antibodies in the pathogenesis of thyroid-associated eye disease. PMID- 11201856 TI - Diurnal thyrotropin secretion in short-term profound primary hypothyroidism: does it ever persist? AB - Circulating serum thyrotropin (TSH) levels in euthyroid humans show a definite circadian variation, which is maintained in both mild hyperthyroidism and mild hypothyroidism. Yet conflicting data exist with regard to whether this variation persists in at least some patients with severe primary hypothyroidism. We, therefore, studied the diurnal variation in serum TSH in 10 patients (age range 20 to 84 years) with a history of thyroid failure due to prior total thyroidectomy and radioiodine (RAI) ablative treatment performed for thyroid cancer after short-term discontinuation of thyroid hormone (TH) therapy. Serum TSH was measured hourly for a 24-hour period. All data were normalized by converting the TSH values to a percentage (%), designating the 11:00 hour value as 100% (baseline). The average serum TSH levels were markedly elevated in all patients. There was no statistically significant difference between the TSH % values at any time during the 24-hour period when compared with baseline. Further, cosine regression analysis showed absence of rhythmicity in TSH % values over time; notably, no patient showed a variation in TSH % values > or = 15% of baseline. In conclusion, diurnal rhythmicity in serum TSH levels was abolished in a uniform cohort of patients with short-term severe primary hypothyroidism. We speculate that the complete lack of peripheral negative feedback input to the hypothalamus or pituitary or both may override the central rhythm-sustaining influences on TSH secretion. PMID- 11201857 TI - Is excessive weight gain after ablative treatment of hyperthyroidism due to inadequate thyroid hormone therapy? AB - There is controversy about the correct dose and form of thyroid hormone therapy for patients with hypothyroidism. Despite restoration of serum thyrotropin (TSH) concentrations to normal, many patients complain of excessive weight gain. We have compared weight at diagnosis of hyperthyroidism with that when euthyroid, evidenced by a stable, normal serum TSH concentration, with or without thyroxine (T4) replacement therapy, in patients treated with an 18-month course of antithyroid drugs (43 patients), surgery (56 patients), or 13I (34 patients) for Graves' disease. In addition, weights were recorded before and after treatment of 25 patients with differentiated thyroid carcinoma by total thyroidectomy, 131I, and long-term T4 suppressive therapy, resulting in undetectable serum TSH concentrations. Mean weight gain in patients with Graves' disease who required T4 replacement therapy following surgery was significantly greater than in those of the same age, sex, and severity of hyperthyroidism rendered euthyroid by surgery (3.9 kg) (p < 0.001) or at the end of a course of antithyroid drugs (4.1 kg) (p < 0.001). Weight gain was similar in those requiring T4 replacement following surgery or 131T therapy (10.4 versus 10.1 kg). In contrast, ablative therapy combined with suppression of TSH secretion by T4 in patients with differentiated thyroid carcinoma did not result in weight gain. The excessive weight gain in patients becoming hypothyroid after destructive therapy for Graves' disease suggests that restoration of serum TSH to the reference range by T4 alone may constitute inadequate hormone replacement. PMID- 11201858 TI - Neutrophilia associated with anaplastic carcinoma of the thyroid: production of macrophage colony-stimulating factor (M-CSF) and interleukin-6. AB - Cancers associated with marked neutrophilia are relatively rare. We report here two cases of anaplastic thyroid carcinoma associated with neutrophilia. We measured the concentrations of granulocyte colony-stimulating factor (G-CSF), macrophage CSF (M-CSF), granulocyte-macrophage CSF (GM-CSF), interleukin-1alpha (IL-1alpha), IL-1beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) in sera, pleural effusion, cyst fluid of the thyroid carcinoma region, or culture supernatants of carcinoma cells. Maximum levels of elevated white blood cell counts reached 106.1 x 10(9)/L (neutrophils 103.0 x 10(9)/L) in case 1 and 62.3 x 10(9)/L (neutrophils 57.9 x 10(9)/L) in case 2. Acute-phase reactants were elevated to various degrees, and hypercalcemia was found in both cases. IL-6, G CSF, and M-CSF seemed to play the principal roles in neutrophilia in case 1, and the elevated levels of IL-6 and M-CSF seemed to mainly contribute to neutrophilia in case 2. Immunohistochemical staining revealed that carcinoma cells themselves produce IL-6 regardless of the types of carcinoma cells. To our knowledge, this is the first report describing the contribution of M-CSF to neutrophilia in patients with thyroid carcinoma. PMID- 11201859 TI - Cost of Care. PMID- 11201860 TI - Moisture chamber for management of corneal ulcer due to Graves' ophthalmopathy. PMID- 11201861 TI - Parathyroid cyst fluid: discrepancy between C-terminal and intact parathyroid hormone assays. PMID- 11201862 TI - Chernobyl tumor bank. PMID- 11201863 TI - The new challenges for chemotherapy research. AB - Scientific knowledge is constantly expanding, and needs are changing; therefore, efforts must be made to adapt the treatment of leprosy and the manner in which it is implemented to the newly identified needs. Because an effective vaccine against leprosy remains to be identified, multidrug therapy (MDT) is the only tool available for leprosy control. At present, therefore, the priority is to make MDT available in all endemic countries for all patients, even those living in difficult-to-access areas. The remaining important issues in chemotherapy research are to improve the quality of leprosy case-finding, improve the quality of MDT, identify the areas in which leprosy patients are not receiving proper MDT, and find the means necessary to ensure delivery to all of appropriate MDT. The MDT regimens recommended by the World Health Organization are of too long duration, require correct classification of the patients as PB or MB, and rely upon the daily self-administration of dapsone and clofazimine to prevent selection of rifampicin resistant mutants among MB patients. Thus, research leading to the development of new drug regimens should be directed toward overcoming the shortcomings of the presently recommended regimens. The drugs required to permit use of regimens of shorter duration, that may be employed among both PB and MB patients, and that enable fully supervised drug administration may be already in hand, and the necessary clinical trials to confirm efficacy and acceptability should be carried out. PMID- 11201864 TI - The epidemiology of reactions and nerve damage. AB - The ALERT MDT Field Evaluation Study (AMFES) in Ethiopia, which was begun in 1988, involves the follow-up of 594 new patients for as long as 10 years after completion of treatment, including 6-monthly assessments of nerve function. In contrast to similar studies in India and Bangladesh, the Ethiopian cohort presented late, had a high rate of disability at diagnosis (55%), a high rate of multibacillary disease (51%) and a high rate of subsequent neuropathy (43%). Preliminary findings include the following. One-third of the patients never exhibited nerve damage. True acute neuropathy has a very good prognosis when treated with a standard course of steroids; full recovery was observed in 88% of nerves. Chronic and recurrent neuropathy have a worse prognosis; these problems need to be identified early and managed appropriately, employing either new steroid regimens or new drugs. The risk factors identified in this study include, for neuropathy, older age, delay of diagnosis, thickened nerves at diagnosis, and reversal reactions. Risk factors for chronic or recurrent neuropathy include classification, impairment at diagnosis, and reversal and ENL reactions. Those factors associated with a poor outcome include impairment at diagnosis, and chronic or recurrent neuropathy. Various problems faced in research in the area of leprosy reactions and neuropathy are discussed, as are the priorities for research in the future. PMID- 11201865 TI - Steroids in leprosy type 1 (reversal) reactions: mechanisms of action and effectiveness. AB - Steroids are widely used for the treatment of leprosy reactions. The effectiveness of steroid treatment is variable, with only 60% of patients regaining nerve function. Sequential skin biopsy specimens, obtained from 15 patients with type 1 (reversal) reactions, have been studied to document the cytokine profile and cellularity of the lesions. All of the patients were placed on a standard course of steroids after the first biopsy. Subsequent biopsies were performed seven, 28 and 180 days later. The specimens were stained for interferon gamma (IFN gamma), interleukin-12 (IL-12) and inducible nitric oxide synthase (iNOS). After the first biopsy, all patients were placed on a standard reducing course of steroids beginning at 30 mg daily. By day 7, treatment with prednisolone showed little effect on the cellularity and cytokine profiles. However, by day 28, significant decreases of IFN-gamma, IL-12 and iNOS were found for most patients. Some patients maintained cytokine production at day 28 and even at day 180. These data illustrate the strong Th1 profile of type 1 reactional lesions, the relatively slow response to therapy, and the continuing activity after treatment with steroids for 180 days. The variation of individual responses emphasizes their importance. Additional prospective studies will be required to determine whether patients with high intra-lesional levels of cytokine are at risk of recurrent reactions. The need for studies both of different glucocorticoids and of other non-steroidal immunosuppressants for the treatment of reactions is discussed. PMID- 11201866 TI - Role of granulysin in immunity to leprosy. PMID- 11201867 TI - Potential of thalidomide and thalidomide analogues as immunomodulatory drugs in leprosy and leprosy reactions. PMID- 11201868 TI - Leprosy research and elimination. AB - The contribution of leprosy research to the progress being made toward elimination of leprosy has been critical. A major development in the promotion of leprosy research during the last 25 years has been the initiative taken by the WHO Special Programme for Research and Training in Tropical Diseases (TDR) through two of its scientific working groups, one on the immunology of leprosy (IMMLEP) and the other on the chemotherapy of leprosy (THELEP), which were set up in 1974 and 1976, respectively. IMMLEP and THELEP have greatly facilitated inputs from scientists not usually active in leprosy research. The coordinated efforts of IMMLEP and THELEP also facilitated goal-oriented research toward high-priority target areas such as an anti-leprosy vaccine and newer and better drug combinations for the treatment of leprosy. Whereas the prospects for a leprosy vaccine appeared very promising in the early years, the first vaccine produced did not meet expectations for several reasons. Moreover, the possibility of using a vaccine in leprosy is not bright, because of both the technical problems as well as the reduced relevance of a vaccine at a time when leprosy is becoming less and less common. On the other hand, the modest expectations for newer and better drug combinations led to multi-drug therapy (MDT) for the control of leprosy. It is the introduction of MDT that is credited with the current global reduction of leprosy and the progress thus far made toward eliminating the disease as a public health problem. Nevertheless, many areas in leprosy, such as nerve damage, remain that require major research inputs in the future. PMID- 11201869 TI - The role of Schwann cells, T cells and Mycobacterium leprae in the immunopathogenesis of nerve damage in leprosy. AB - Damage to peripheral nerves is the major complication of reversal (type I) reactions in leprosy. The underlying mechanism of nerve damage remains largely unresolved; however, an important role for type-1 T cells has been suggested. Mycobacterium leprae has a remarkable tropism for the Schwann cells that surround peripheral axons. Because reversal reactions in leprosy are often accompanied by severe and irreversible nerve destruction, and are associated with increased cellular immune reactivity against M. leprae, a likely immunopathogenic mechanism of damage to Schwann cells and peripheral nerves in leprosy is that infected Schwann cells process and present antigens of M. leprae to antigen-specific, inflammatory, type-1 T cells, and that these T cells subsequently damage and lyse infected Schwann cells. Previous animal studies with CD8+ T cells revealed evidence for the existence of such a mechanism. A similar role has been suggested for CD4+ T cells. These latter cells may be more important in causing nerve damage in vivo, given the predilection of M. leprae for Schwann cells, and the dominant role of CD4+, serine esterase+ Th1 cells in the lesions of leprosy. Antagonism of the molecular interactions among M. leprae, Schwann cells and inflammatory T cells may therefore provide a rational strategy for prevention of damage of Schwann cell and nerves in leprosy. PMID- 11201870 TI - Dysregulation of IL-4 expression in lepromatous leprosy patients with and without erythema nodosum leprosum. AB - In order to increase our understanding of the immunological basis of erythema nodosum leprosum (ENL), we studied Th-like cytokine profiles in 130 leprosy patients, employing both the conventional and a novel, real-time, fluorogenic reverse transcriptase-based PCR (RT-PCR). The concomitant expression of both Th like cytokines, interferon-gamma and IL-4, and the regulatory cytokines, IL-10 and IL-12, was studied in the peripheral blood cells of leprosy patients with and without ENL. In the conventional RT-PCR, varied cytokine profiles were observed in individual patients of all clinical types. Fifty-three percent of lepromatous patients without ENL and 59% of tuberculoid leprosy patients showed co-expression of IFN gamma and IL-4, indicating a non-polarized Th 0 pattern. Of the 36 patients with ENL, 58% demonstrated a polarized Th 1 pattern, with only 30% expressing both cytokines. Semiquantitative RT-PCR indicated a lower expression of IL-4 compared to that of IFN gamma in the lepromatous patients without ENL; the difference was even greater among those with ENL. The sensitive, real-time PCR confirmed the down-regulation of IL-4 and IL-10, with absence of IL-4 in half of the patients, resulting in skewing of the cytokine response toward a Th 1-like profile. PMID- 11201871 TI - Review of current research in the prevention of nerve damage in leprosy. AB - Nerve damage and the consequences of nerve damage set leprosy apart from other diseases. The irreversible motor and sensory impairments caused by leprosy lead to increasing secondary impairments long after the disease process has been arrested. Interventions that prevent, reverse or limit the impairments resulting from leprosy are, therefore, of the highest priority. Self-care has been demonstrated to be an effective means of preventing secondary tissue damage, and its implementation must now be encouraged within the framework of basic health care. Currently, a comprehensive effort has been made to address all dimensions of impairment of nerve function and its consequences, from prevention of both primary and secondary impairments to interventions in long-term nerve damage. The BANDS prospective study of a cohort of 2664 previously untreated leprosy patients in Bangladesh has provided both a valuable baseline and insight into the epidemiology of nerve damage in leprosy. This work has defined the numbers of patients who present with acute nerve damage, the numbers who are not treated, and the importance of the MB classification, and has described the simple clinical prediction rule. This study also provided the basis for the development of the three TRIPOD randomized clinical trials in Nepal and Bangladesh. Follow-up of the BANDS cohort, which is continuing, will yield more data on the natural history of nerve damage. The encouraging results from the TRIPOD trials of low dose prophylactic steroids will be followed up, to see whether the effect is sustained over time. The TRIPOD trials are to be completed, a trial of three steroid regimens in reversal reaction is to be completed, and a number of specific research topics within the ILEP programme, INFIR, are to be developed. PMID- 11201872 TI - Peripheral neuropathy in leprosy and its consequences. AB - Leprosy causes a 'mononeuritis multiplex' of immunological origin that results in autonomic, sensory and motor neuropathy. When detected and treated early, primary impairments may be reversible. However, 11-51% of patients do not recover. In addition, 33-56% of newly registered patients already have clinically detectable impairments, often no longer amenable to drug treatment. Among new patients, 6 27% present with secondary impairments, such as wounds, contractures and shortening of digits. All patients with impairments should be taught methods to prevent further impairment and subsequent disability (POID). As the result of impairments, many people experience limitation of activities of daily living, which can be partially overcome with the help of assistive devices, training, and surgery. As a result of these limitations, because of visible impairments, or simply because of the diagnosis 'leprosy', many people are restricted in their participation in society. Many overcome activity limitations and participation restrictions without assistance, despite residual impairments. However, some require intervention, such as physical or occupational therapy, reconstructive surgery or temporary socioeconomic assistance. Information on these issues is not collected routinely, and the few tools that exist to measure the severity or extent of impairment have not been widely used, nor have they been used to generate cohort-based statistics. There are no agreed indicators for monitoring POID activities or rehabilitation interventions. Work in the general field of rehabilitation has resulted in the ICIDH-2, which provides a conceptual framework for rehabilitation and the entire area of 'consequences of health conditions'. Although experience to date is very limited, the conceptual framework appears appropriate to leprosy. Data on the prevalence and incidence of primary and secondary impairments have been reported from several countries, the link between impairments and activity limitations has been investigated, and a few studies of the magnitude of the need for rehabilitation have been reported. Research priorities include studies of methods to improve detection of autonomic, sensory and motor neuropathy; trials of alternative drugs or regimens for treating neuropathy; studies of the use of various POID-monitoring systems that may be derived from these; studies of the design and use of instruments to assess limitations of activities and restrictions on participation; assessments of needs for rehabilitation and the development of methods to do these; studies of the efficacy of various types of rehabilitation interventions for particular conditions; and studies of the cost-effectiveness of such interventions. PMID- 11201873 TI - Pathogenesis of nerve damage in leprosy: genetic polymorphism regulates the production of TNF alpha. AB - Studies carried out over the last decade have strongly suggested that TNF alpha both overtly participates in the cell-mediated immune response against Mycobacterium leprae, and is overproduced during reaction. In addition, reactions are intimately related to the onset of nerve damage. Finally, TNF alpha has been implicated in the pathogenesis of many human and experimental autoimmune peripheral neuropathies that, as in leprosy, result in demyelination and axonal lesions. Because of recent findings associating human TNF alpha mutant alleles at the -308 position with increased production of TNF alpha in many immunological and infectious diseases, an investigation of the role of TNF2 in predisposing leprosy patients to reaction has been undertaken. Analysis of 300 patients with leprosy--210 multibacillary and 90 paucibacillary--has shown that the percentage of reactional patients was similar among both carriers and non-carriers of the TNF2 allele. However, a separate analysis of 57 carriers of TNF2 found that reactions occurred much more frequently among heterozygous than among homozygous patients. Moreover, the frequency of neuritis was somewhat greater among the heterozygous patients than among the non-carriers. Enhanced serum levels of TNF alpha have been noted in both TNF-1 and TNF-2 mutant patients in the course of leprosy reaction. Our observations to date suggest that other factors not related to the presence of the mutant gene may lead to the TNF alpha hyper-responsiveness observed during reaction. PMID- 11201874 TI - Prophylaxis--scope and limitations. AB - Attempts to prevent leprosy by one or another prophylactic method began with the use of dapsone as a chemoprophylaxis. Following early, small-scale studies, which were promising, large-scale studies with dapsone and acedapsone, both among contacts and in the general population, demonstrated that it is possible to prevent the occurrence of leprosy to a modest extent. With regard to immunoprophylaxis, BCG had long been considered a possibility, particularly in view of its potential to convert the skin test reaction to lepromin. Over the years, major, large-scale field trials of BCG had been carried out in Uganda, Burma, Papua New Guinea and India. All of the studies demonstrated that BCG was capable of preventing leprosy. However, protective efficacy varied from around 20% to greater than 80%. Killed Mycobacterium leprae mixed with BCG has also given varying results. Other vaccines based on cultivable mycobacteria have also been tried, and at least one of them appears promising. An approach to prophylaxis must take into account (a) the level of risk addressed and the perception of risk by the community; (b) the level of efficacy of the method of prophylaxis; (c) the possibility of easily identifying high-risk groups; (d) the operational feasibility; and (e) the focus of the prophylaxis, whether the individual or the community, or both. However, in view of the enormous progress being made towards elimination of leprosy by the widespread application of MDT, prophylaxis is becoming less and less relevant and less and less cost-effective, except in very special situations. PMID- 11201875 TI - Preliminary analysis of the genome sequence of Mycobacterium leprae. PMID- 11201876 TI - Molecular basis of the interaction of Mycobacterium leprae with peripheral nerve: implications for therapeutic strategies. PMID- 11201877 TI - Exploitation of gene knockout mice models to study the pathogenesis of leprosy. AB - Shepard's technique for growth of Mycobacterium leprae in the mouse footpad, described in 1960, and more recent studies in thymectomized-irradiated mice and rats, athymic nude mice, nude rats and severe combined immunodeficiency (SCID) mice have defined the role of T-cell mediated immunity (CMI) in leprosy. However, the normal mouse and the immunocompromised mouse and rat represent only elements of polar tuberculoid disease and polar lepromatous leprosy, respectively. Transgenic, knockout (KO) mice may be employed to study the roles of individual genes in the ability of the host to mount an effective immune response to pathogens, and may also allow development of mouse models for the immunologically unstable borderline areas of the spectrum. We are exploiting certain KO mice to improve our understanding of CMI to M. leprae, and to study the role of the microenvironment of the leprosy granuloma in pathogenesis. CGD (chronic granulomatous disease) mice and iNOS-KO mice lack the ability to produce reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI), respectively, whereas the T cells of GKO mice are unable to produce interferon gamma (IFN gamma). iNOS-KO mice exhibit an enhanced capacity to form granulomas, and the histopathology of the infected footpad tissues of this strain share many elements of borderline tuberculoid disease. The macrophages of CGD mouse kill or inhibit multiplication of M. leprae, although they lack ROI. Multiplication of the organisms in the footpad is enhanced in GKO mice, although these mice retain some host resistance. In addition, we have been investigating supplementary, conditional approaches to KO mouse models. For example, the down-regulatory effects of local prostaglandin production can be controlled with essential fatty acid deficient diets or indomethacin, RNI can be blocked in CGD and GKO mice by treatment with aminoguanidine, NG monomethyl arginine or N6-(1-iminoethyl)-L lysine, and local elaboration of TNF alpha can be neutralized by anti-TNF alpha antibody or excess TNF alpha receptor. Other cytokines can be neutralized by antibody as well, broadening the range of conditional knockout models. PMID- 11201878 TI - Immunoprophylaxis against Mycobacterium leprae infection with subunit vaccines. AB - We have investigated the effect of subunit vaccines against infection with Mycobacterium leprae, employing DNA plasmids as the vaccine vectors, and the immunodominant 35 kDa protein of M. leprae as the candidate antigen. A DNA vaccine that expresses the M. leprae 35 kDa protein both stimulated interferon gamma (IFN gamma)-secreting T cells in mice, and demonstrated protection against M. leprae-infection of mice. PMID- 11201879 TI - Leprosy research--setting priorities and facilitating collaborations: a personal perspective. AB - In recent years, as the prevalence of leprosy has declined and the tuberculosis epidemic has gained increasing attention, leprosy research has generally taken a 'back seat' to research in tuberculosis and other emerging and re-emerging infections. This has resulted as much from perceived differences of scientific opportunities in these fields as from differences of the disease burden. At the United States National Institutes of Health (NIH), research priority setting is typically based on a number of factors. In the case of leprosy research, the technical difficulties associated with this scientific area have clearly lessened enthusiasm for and progress in this field. Today, however, we are confronted by the reality of not having sufficient scientific understanding to explain a stable or increasing number of leprosy cases detected annually in the face of a dramatically decreasing total number of identified cases. We also lack adequate tools for diagnosis and prevention. At the same time, new molecular and cellular approaches and knowledge of the complete sequence of the genome of Mycobacterium leprae render leprosy research significantly more tractable than ever before. The combination of these factors has led a number of groups, including the National Institute of Allergy and Infectious Diseases of the NIH, to review the current state of knowledge in leprosy research and draft recommendations for future leprosy research priorities. It is clear that many of the necessary and exciting research activities can best be addressed through collaborations among investigators, with control programmes, and among countries of high and low endemicity. PMID- 11201880 TI - Research component in the global alliance. PMID- 11201882 TI - Approaches to studying the transmission of Mycobacterium leprae. AB - A collaborative study has been undertaken to establish the relationship between infection by Mycobacterium leprae and the development of immunity in a community in which multidrug therapy (MDT) has been used for more than 10 years, to elucidate the pathogenesis of infection in leprosy, and to develop and test an intervention strategy based on chemotherapy for interruption of transmission of the organism in the community. The first phase of the study included the establishment of laboratory facilities and pilot work in India. In the course of the second phase, the entire populations of three villages in India and one in Ethiopia have been surveyed, nasal swabs were obtained for detection of M. leprae DNA by means of the polymerase chain reaction (PCR), specimens of saliva were obtained for measurement of levels of anti-M. leprae IgA antibodies, and follow up surveys have been carried out. A double-blind trial of chemotherapy among subjects whose PCR was positive is proposed, to determine if the course of the infection can be influenced by treatment. The performance of large numbers of PCR tests in endemic countries has required the development of rigorous internal and external quality control procedures. These have shown that many batches (as many as 50%) fail to meet quality control criteria, and must be retested. Despite this, development of these methods, and their application to field studies should provide tools for studying the transmission of M. leprae, and direct methods of testing innovative interventions. PMID- 11201881 TI - Leprosy chemoprophylaxis in Micronesia. AB - A programme of chemoprophylaxis was introduced as a component of the leprosy control programme in the Federated States of Micronesia (FSM), beginning in 1996. The entire population of the country was to be screened, and a single dose of 600 mg rifampicin, 400 mg ofloxacin and 100 mg minocycline (ROM) was to be administered to the entire population. Two rounds of screening the entire population were carried out, approximately 1 year apart, and chemoprophylaxis was administered at the time of each screening. Ninety percent of the population were screened at least once, and 55% were screened in both rounds; 87% of the population received at least one dose, and 54% received two doses. In the course of the first round, 322 new cases were detected, whereas only 80 new cases were detected during the second round, of whom only 12 had received chemoprophylaxis in the course of the first round. A third round of screening, confined to a small number of villages in both Chuuk and Pohnpei, in which states leprosy endemicity was high, was carried out approximately 2 years after the second. Only 16 new cases were detected during the third round of screening, whereas 102 new cases had been detected in this same population during the first round of screening, and 32 new cases during the second. Six of the 16 newly detected cases stated that they had been administered chemoprophylaxis at least once; however, this information may not be reliable. PMID- 11201883 TI - Strategies for pro-active case-finding in leprosy control. PMID- 11201884 TI - Chemoprophylaxis of leprosy in the southern Marquesas with a single 25 mg/kg dose of rifampicin. Results after 10 years. AB - In 1988, a programme of leprosy chemoprophylaxis, employing a supervised, single 25 mg/kg dose of rifampicin, was implemented in the Southern Marquesas Islands. Of the 2786 inhabitants, 2751 (98.7%) were treated. In addition, 3144 South Marquesans living elsewhere in French Polynesia were administered the same chemoprophylaxis. During the following 10 years, seven leprosy patients were detected among those who had been administered chemoprophylaxis. Of these, two were very likely missed cases of leprosy, and cannot be considered a failure of chemoprophylaxis. The epidemiometric projection model, based on cases of leprosy observed in the Southern Marquesas during the 20 years preceding implementation of the programme, predicted that 17 leprosy cases could be expected in the South Marquesan population if no chemoprophylaxis were given. In fact, only five cases were detected in the treated population, a number significantly smaller than 17, suggesting that the chemoprophylaxis was 70% effective, assuming that no change of detection rate would have occurred without chemoprophylaxis. However, during the 10 years following implementation of the chemoprophylaxis programme, the detection rate in the Polynesian population that was not administered chemoprophylaxis declined by about 50%. Therefore, the effectiveness of the chemoprophylaxis was only 35-40%. PMID- 11201886 TI - South India immunoprophylaxis trial against leprosy: relevance of the findings in the context of trends in leprosy. PMID- 11201885 TI - Chemoprophylaxis against leprosy: expectations and methodology of a trial. AB - Because of the great efficacy of multidrug therapy (MDT), it had been hoped that the widespread use of MDT would bring about a rapid decrease of the incidence of leprosy. To the present, a decrease of incidence has not been observed, possibly because of the long incubation period of the disease, and because general implementation of MDT is still recent. Other reasons, such as environmental sources of infection or the role of healthy carriers in transmitting Mycobacterium leprae, cannot be excluded. Therefore, one must seek alternative or supplementary strategies, such as chemoprophylaxis. Household contacts of leprosy patients are at greater risk of developing leprosy than is the general population. Therefore, a randomized, controlled trial of chemoprophylaxis, using a single 10 mg/kg dose of rifampicin, or a placebo, is planned in nine projects in India, among the household contacts of newly detected leprosy patients. Based upon assumptions of a protective efficacy of the chemoprophylaxis of 50%, an annual incidence of 2 per 1000 contacts, a desired power of the study of 90%, and a level of significance of 95%, 15,000 household contacts will be allocated randomly by household to each arm of the study, and followed for 5 years. Considered as household contacts will be all persons living in the same household as an index case and sharing the same kitchen. Pregnant women and infants will be excluded. To be certain that transmission of the organisms from the index case cannot occur once the prophylaxis is administered, rifampicin will be administered 2 months after diagnosis of the index case. Diagnosis of leprosy will be clinical, and confirmed independently. Although household contacts usually constitute only a small proportion of the new patients detected in a control programme, their high-risk status makes them particularly appropriate for a study of the potential effect of chemoprophylaxis. Following the trial, one could evaluate the usefulness and feasibility of using the same strategy in other population-groups, based on the number of persons necessary to treat to prevent one case. PMID- 11201887 TI - Skin test development in leprosy: progress with first-generation skin test antigens, and an approach to the second generation. AB - One of the most urgent needs from leprosy research is a test for infection. The lepromin test is not suitable as a diagnostic test for leprosy, and neither the Rees nor the Convit soluble antigens has appeared sufficiently specific. Because two new antigens, MLSA-LAM and MLCwA, may not fully meet the requirements for specificity, we have embarked upon the preparation of a second generation of skin test antigens. Size-fractionated cryptozoic proteins were prepared from M. leprae by electroelution from preoperative sodium dodecylsulphate-polyacrylamide gel electrophoresis, and individual fractions were probed with polyclonal and monoclonal antibody reagents to identify both known and novel proteins. In addition, immunological responses were assessed in M. leprae-sensitized guinea pigs against both crude subcellular fractions (cytosol, membrane, and soluble cell wall proteins) and the size-fractionated cytosolic proteins. A particularly promising subcellular fraction is the membrane fraction of M. leprae, which contains many proteins unique to the organism. Clinical trials of the M. leprae membrane proteins are now being planned. PMID- 11201888 TI - Diagnostic assays for leprosy based on T-cell epitopes. AB - To date, only a limited number of antigens have been described as specific for Mycobacterium leprae, and in many cases, homologues have subsequently been shown to exist in mycobacteria such as M. avium and M. intracellulare. A Leprosy Synthetic Peptide Skin Test Initiative was established by the Steering Committee on the Immunology of Mycobacteria of the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases, to investigate the potential of synthetic peptides that encode T-cell epitopes as diagnostic tools, which could be used to develop a skin-test reagent specific for leprosy. Such M. leprae specific peptides should have unique amino acid sequences, or significant sequence-dissimilarity from those in other mycobacteria. Synthetic peptides, 15 amino acids long, were synthesised from 33 genes or open reading frames within the M. leprae genome. Tuberculoid leprosy patients from four leprosy-endemic countries, Brazil, Ethiopia, Nepal and Pakistan, were tested as subjects known to have been infected with M. leprae, and to make good T-cell responses to antigens of M. leprae; UK blood donors were used as non-exposed or non-infected subjects. Peptides inducing potentially specific responses in leprosy patients and not in UK controls, and those inducing cross-reaction responses, present in both leprosy patients and non-exposed, non-infected controls, were identified. A difference from the equivalent M. tuberculosis sequence of five or more amino acid residues did not, by itself, identify peptides that were M. leprae-specific, suggesting that many of these peptides may have homologues in environmental mycobacteria. To date, this approach has identified a number of peptides with greater than 90% specificity and 19-47% sensitivity, which are undergoing further specificity testing. Such peptides would have great potential as T-cell reagents with which to monitor exposure to M. leprae within communities, formulated either as skin test reagents, or as antigens for tests in vitro. PMID- 11201889 TI - Whole blood assays for interferon-gamma: practicalities and potential for use as diagnostic tests in the field. AB - Recent years have seen the introduction of a number of whole-blood assays, in which unseparated heparinized blood is stimulated with antigen either overnight or for as long as 6 days, and cytokine production is measured in the plasma or supernatant. These assays have potential for use in the field as immunodiagnostic assays, as they require only a small blood sample and basic laboratory facilities. Use of these assays in a large study of the immunological effects of BCG vaccination in Malawi has shown that the diluted blood, 6-day whole-blood assays is robust, and can be used to assess T-cell responses to both crude and recombinant antigens. If used with antigens specific to Mycobacterium leprae, these assays could be used to measure exposure of M. leprae within communities or populations, or to aid the early diagnosis of leprosy. PMID- 11201890 TI - Experience and lessons from the use of lepromin and Mycobacterium leprae-specific serology. AB - Skin testing with lepromin, which produces a delayed-type hypersensitivity reaction, has been used in the classification of leprosy, and a good correlation has been found between immunological status and the reaction to lepromin. In addition, the prognostic value of the lepromin test has been demonstrated. More recently, skin testing with two soluble antigens of Mycobacterium leprae showed no difference of the mean size of the reaction between household contacts and non contacts, indicating that these antigens are not useful for the diagnosis of leprosy. This and other evidence points to the need for a better skin test antigen capable of detecting infection of individuals by M. leprae. Whereas serological assays for antibodies against both PGL-1 and the 35 kDa antigen of M. leprae have been found to yield positive results in 90-100% of patients with lepromatous (BL/LL) leprosy, these assays fail to identify 40-60% of patients with tuberculoid (BT/TT) leprosy, because of the presence of only an insignificant level of antibody against components of M. leprae in these patients' serum, although, in many BT patients, antibody signal could be detected in the local lesions. These data indicate that there remains a need for a specific diagnostic test for leprosy. PMID- 11201891 TI - Use of a Mycobacterium leprae dipstick to classify patients with leprosy. PMID- 11201892 TI - A rapid, microplate-based assay for evaluating the activity of drugs against Mycobacterium leprae, employing the reduction of Alamar Blue. PMID- 11201893 TI - Field trials of a single dose of the combination rifampicin-ofloxacin-minocycline (ROM) for the treatment of paucibacillary leprosy. PMID- 11201894 TI - Combination of rifapentine-moxifloxacin-minocycline (PMM) for the treatment of leprosy. AB - To further the development of a multidrug regimen for treatment of leprosy that is suitable for monthly administration and fully supervisable, the bactericidal activities against Mycobacterium leprae of HMR 3647 (HMR), moxifloxacin (MXFX) and rifapentine (RPT) were measured by the proportional bactericide technique in the mouse footpad system, and compared with those of the established antileprosy drugs clarithromycin (CLARI), ofloxacin (OFLO) and rifampicin (RMP). Administered in five daily doses of 100 mg per kg body weight, HMR appeared slightly more bactericidal than CLARI, but the difference did not attain statistical significance. Administered as single doses, MXFX in a dosage of 150 mg per kg was more active than OFLO in the same dosage, and displayed the same level of activity as RMP in a dosage of 10 mg per kg; the combination MXFX-minocycline (MINO) (MM) was more bactericidal than the combination OFLO-MINO (OM); RPT in a dosage of 10 mg per kg was more bactericidal than RMP administered in the same dosage, and even more active than the combination RMP-OFLO-MINO (ROM); the combination RPT-MXFX-MINO (PMM) killed 99.9% of viable M. leprae, and was slightly more bactericidal than was RPT alone, indicating that the combination PMM showed an additive effect against M. leprae. These promising results justify a clinical trial among lepromatous patients, in which MM is being compared with OM, and PMM with ROM, in terms of efficacy and tolerance. PMID- 11201895 TI - Current World Health Organization-sponsored studies in the chemotherapy of leprosy. PMID- 11201896 TI - Dapsone resistance in Mycobacterium leprae. AB - The folP1 gene of Mycobacterium leprae, which encodes dihydropteroate synthase (DHPS), was studied for the presence of mutations associated with resistance to dapsone (DDS). When the folP1 of several DDS-resistant clinical isolates of M. leprae were sequenced, two missense mutations were identified. One mutation occurred at codon 53, substituting isoleucine for threonine in DHPS-1, and a second mutation occurred in codon 55, substituting arginine for proline. DNA sequencing of strains of M. leprae resistant to 0.01 g% DDS in the mouse diet revealed that 13 of 14 strains contained either the 53 or 55 folP1 mutation. None of the susceptible strains and only one of five strains resistant to 0.001 g% DDS revealed a mutation in folP1, suggesting that only high-level DDS resistance is associated with the mutations identified in folP1. Development and application of simple molecular tests to assess drug-related mutations in M. leprae could establish current levels of drug resistance in leprosy as a reference point for future monitoring of drug resistance at the global level. PMID- 11201897 TI - Rapid detection of resistance to rifampicin in Mycobacterium leprae. PMID- 11201898 TI - Consequences of leprosy and socio-economic rehabilitation. PMID- 11201899 TI - Implementing guidelines for socio-economic rehabilitation. PMID- 11201900 TI - Guidelines for social and economic rehabilitation. PMID- 11201901 TI - Socio-economic rehabilitation programmes of LEPRA India--methodology, results and application of needs-based socio-economic evaluation. AB - There is now a better understanding of the scope and process of rehabilitation. The approach recognizes the impact of leprosy on the individual, aims to understand the needs and concerns of those affected, their families and community in the rehabilitation process, and that aims to restore the person to normal social life. LEPRA India has undertaken socio-economic rehabilitation (SER) activities in its projects in Andrah Pradesh and Orissa States in India with a holistic approach that has been evolutionary, developmental and participatory. A SER Officer (SERO) was posted to each project. A plan was formulated by the SERO with participation of all project staff. The main emphasis of the programme was on active participation of the affected person in the rehabilitation process. A needs-assessment study was conducted in the target population using a semi structured questionnaire. Information was elicited about social and economic status, before and after the disease, and the current rehabilitation needs of the persons affected. The next step was meeting the needs through interventions by the SER staff. The impact of the programme on restoration of social and economic status of the affected persons was analysed. The paper stresses the importance of assessing the needs of persons affected by leprosy, structuring a rehabilitation programme with the active participation of the affected person and evaluating the impact of the interventions in restoring normal social and economic life. PMID- 11201902 TI - Making sense of rehabilitation projects: classification by objectives. AB - Rehabilitation of disabled persons can take many different forms according to the socio-cultural and political context in which it is undertaken. Some approaches have emphasized the restoration of the physical function of the client, while others have looked beyond to psychological and social well-being. Some have built on the expertise of professionals while others have emphasized the caring capacity available in the family and the community and sought to reinforce it. Besides providing a wide range of possible services to disabled persons, rehabilitation seeks to change the attitudes that prevail in society as a whole and promote the integration of disabled people into society with equal rights and opportunities. This paper reviews a range of models and approaches which have been put forward in the international debate on rehabilitation. Furthermore, four dimensions are described which can be used to characterize and define classes of rehabilitation projects based on the objectives that are defined for them. Thus types of rehabilitation projects can be distinguished. Management, evaluation and technical support for rehabilitation projects need to take these essential characteristics into account. PMID- 11201903 TI - The psychosocial needs of leprosy patients. PMID- 11201904 TI - Leprosy: between acceptance and segregation. Community behaviour towards persons affected by leprosy in eastern Nepal. AB - This study describes community behaviour towards persons affected by leprosy in the eastern Terai districts of Nepal. The results show that 95% of the persons affected by leprosy recognized by the community have visible signs such as wounds, swellings and deformed feet or hands. Persons affected by leprosy still experience negative behaviour. Motives for negative community behaviour are mostly found in the fact that people fear infection by germs, but fear of a curse from God is also mentioned. This study shows that negative community behaviour is still present in eastern Nepal. Leprosy is more than a disease; the disease can nowadays be medically cured, but the sickness of leprosy still remains. Leprosy control programmes should focus on prevention of impairments and disabilities, because it seems that a visible sign is an important trigger for negative community behaviour. PMID- 11201905 TI - Stigma reduction through group counselling of persons affected by leprosy--a pilot study. AB - Stigmatization of persons with leprosy causes the emotional harm of social, economic and spiritual deprivation. Individual counselling has benefits in addressing these psychosocial problems but is a slow process and effects few people at any one time. Our experience of group counselling of stigmatized persons achieved the following: addressing common issues to more than one person at a time, encouraging the unity of sufferers, developing compassion for others, understanding the common effects of stigmatization, and beginning to overcome its harmful effects. PMID- 11201906 TI - Gender differentials in the social and family life of leprosy patients. AB - A study was carried out at the Leprosy Control Unit, Government Medical College, Nagpur, India, to investigate gender differentials in the social and family life of leprosy patients. The study included 486 (268 males and 218 females) leprosy patients, who were diagnosed and registered at least 1 year prior to the data collection. It was observed that leprosy patients were isolated and refrained from various activities in the family. However, the effect of disease on this isolation was significantly greater in females as compared to males. Similarly, although, men and women were both affected in terms of their social life, women suffered more isolation and rejection from the society. The current study describes the gender differentials in the social and family life of leprosy patients in Central India. PMID- 11201907 TI - Delay in presentation and start of treatment in leprosy: experience in an out patient clinic in Nepal. AB - Delayed presentation is a recognized risk factor for disability in leprosy but is the result of complex interactions between physical, social, economic and psychological factors. The present study is a response to the situation in an outpatient clinic in Nepal where the wide variation in delay in presentation was a cause for concern. A purpose-written questionnaire was used to collect information on 166 consecutive outpatient admissions. The data included demographics, the first symptom of leprosy, first actions, initial help-seeking behaviour, the reasons for finally seeking treatment and experience with professional health services. Initial analysis found a relationship between delay in presentation and age, rural environment, leprosy classification, walking time, housing not shared with another person affected by leprosy, and an inappropriate first action. The relationship with lack of education and total travel time just failed to reach significance. Further analysis identified that for the study population initial lack of awareness of leprosy and an inappropriate first action were the primary contributors to delay. Extensive and effective health education is needed to address this situation. PMID- 11201908 TI - Small loan schemes: the experience of Ethiopia. PMID- 11201909 TI - Evaluation of a housing programme. PMID- 11201910 TI - Unmet needs of rehabilitation in leprosy services. PMID- 11201911 TI - Ophthalmologic screening of deaf students in Oregon. AB - PURPOSE: To determine the frequency of Usher's syndrome and other ocular disease in students receiving special education services for the deaf in Oregon and to assess the amount of existing ophthalmologic surveillance of this population. A special emphasis was placed on screening for Usher's syndrome. METHODS: From 1980 1990, a prospective two-center visual screening program of 231 deaf students in schools throughout Oregon was conducted using an ophthalmic questionnaire, complete eye examinations, and electroretinography. Students were between the ages of 10 and 21 years and participated on a volunteer basis. Findings for etiology and severity of visual loss and the scope of ophthalmologic surveillance within this population were analyzed. RESULTS: Two hundred seventeen of the 231 students examined received electroretinograms. Significant ocular pathology was found in 111 (48%) of the students. The most common diagnoses were congenital rubella (21%), significant uncorrected ametropia (16%), and ocular hypertension (9%). Five students were diagnosed with Usher's syndrome. Of the students with significant ocular pathology, only 37% were actively followed by an ophthalmologist. CONCLUSION: Deaf students in Oregon's schools had a high frequency of eye disease. Early diagnosis and treatment of eye disease in this population could benefit the quality of life of these students. This study alerted the providers of special education services for the deaf and the ophthalmologic community in Oregon of the need for better eye care for these students. PMID- 11201912 TI - Cataract surgery in children with uveitis. AB - PURPOSE: To report the technique and postoperative results of cataract surgery in children with uveitis. METHOD: Between 1988 and 1998, nine children (age range: 2.5-11 years) who developed secondary uveitic cataract and underwent cataract extraction were studied retrospectively. Seven children had juvenile rheumatoid arthritis and two had chronic anterior uveitis of unknown etiology. The surgical technique was lensectomy and wide anterior vitrectomy with limbal approach, lysis of anterior synechiae and in some cases, peripheral iridectomy. Postoperative aphakia was corrected with soft contact lenses in all patients. Follow-up ranged from 6 months to 6 years. RESULTS: Postoperatively, visual acuity in all patients improved and final visual acuity ranged from 20/70 to 20/25. Significant intraoperative complications did not occcur in any patient. One boy with juvenile rheumatoid arthritis developed cystoid macular edema 1 month postoperatively, which was successfully managed. He also developed hypertonia 1 year later, which was also successfully managed. Seven of the nine children had fewer and milder relapses of uveitis after surgery. CONCLUSION: Cataract surgery, using the lensectomy-vitrectomy technique in children with uveitis, is a safe technique with a relatively small percentage of postoperative complications and good functional results. PMID- 11201913 TI - Comparison of visual evoked potentials in patients with psychogenic visual disturbance and malingering. AB - PURPOSE: To verify the efficiency and objectivity of the pattern visual evoked potential (VEP) for organic disorders of the cortical visual system. METHODS: This retrospective study evaluated VEP in 19 patients diagnosed with psychogenic visual disturbance, 7 patients with malingering, and 37 age-matched normal volunteers. Transient (3 reversals per second) and steady-state (12 reversals per second) pattern VEPs for check sizes 15' and 30', with a contrast of 80%, were recorded. RESULTS: The amplitudes of both transient and steady-state pattern VEPs were significantly increased in patients with psychogenic visual disturbance, while patients with malingering had significantly lower amplitudes. P100 peak latency was prolonged in both groups of patients. CONCLUSION: Monitoring of patients' fixation on the stimulus showed those with psychogenic visual disturbance fixated well on the stimulus, while those with malingering did not. This finding produced a VEP amplitude reduction in patients with malingering. The reason for the VEP amplitude in patients with psychogenic visual disturbance is unclear. PMID- 11201914 TI - Effects of anisometropia on binocularity. AB - PURPOSE: To investigate the effects of anisometropia on binocular function and the relationship between stereopsis and fusion in anisometropia. METHODS: Twenty five patients with anisometropia were studied. The manifest refraction and best corrected Snellen visual acuity of each patient was recorded. Patients, corrected with spectacles, were evaluated using Bagolini glasses, the 4-diopter (D) prism test, Worth four-dot test, and TNO stereotest. RESULTS: All patients indicated fusion by the Bagolini glasses. Although the 4-D prism test was positive in the anisometropic eye of all 25 patients, it was slower than the response of the other eye in 19 patients with reduced stereoacuity. On the distant Worth four-dot test, fusion response was positive in 15 patients. On theTNO test, stereoacuity levels were reduced or absent in 19 patients. CONCLUSION: The depth of amblyopia is more effective than the amount of anisometropia in causing a deterioration in binocularity. Even if fusion is weak, almost all patients with anisometropia have bifoveal fusion. Fusion becomes weak and stereoacuity decreases in proportion to the anisometropic amblyopia. Stereoacuity is related to the strength of fusion, and the TNO stereotest effectively detects those patients with significant anisometropic amblyopia. PMID- 11201915 TI - Managed care dominance. PMID- 11201916 TI - A 5-year old boy presented with congenital nystagmus. PMID- 11201917 TI - Iris hamartomas presenting without neurofibromatosis. PMID- 11201919 TI - Severe bilateral ocular features in Goldenhar's syndrome. PMID- 11201918 TI - Retinopathy due to juvenile polymyositis. PMID- 11201920 TI - Association of keratoconus and Mobius' syndrome. PMID- 11201921 TI - Bacterial endocarditis following lacrimal duct probing. PMID- 11201922 TI - Nursery light levels in the LIGHT-ROP study. PMID- 11201923 TI - Visual impairment in children with acute nontraumatic coma. AB - PURPOSE: To determine the incidence and severity of visual impairment in children following acute nontraumatic coma. METHODS: An 18-month prospective epidemiologic study of acute nontraumatic coma was undertaken in the former Northern NHS Region of England. Children aged >1 month and <16 years were included in the study if they had a Glasgow Coma Score of < or = 12 for >6 hours or if they died within 6 hours of the onset of decreased levels of consciousness. For survivors, ophthalmologic assessments were performed 6 weeks and 12 months after presentation. RESULTS: Two hundred eighty-seven children were included in the study, of whom 127 died. Of the 137 examined survivors, 35 had visual abnormalities suspected by the examining neurologist during the ophthalmic assessment. Of these, visual impairment was confirmed in 10 children at the 6 week assessment by the pediatric ophthalmologist. At the 1 2-month assessment, visual impairment remained stable in 9 children and improved in 1. CONCLUSION: In this study, 6.6% of children surviving acute nontraumatic coma had visual impairment that persisted at the 12-month follow-up examination. Incidence of visual impairment in acute nontraumatic coma is 0.97 per 100,000 children per year. PMID- 11201924 TI - Women's recreational ice hockey injuries. PMID- 11201925 TI - Involuntary psychiatric treatment is not to be decided by psychiatrists. PMID- 11201926 TI - Commentary: involuntary psychiatric treatment is a medical decision. PMID- 11201927 TI - Commentary: involuntary psychiatric treatment must be decided by the district psychiatrist. PMID- 11201928 TI - Commentary: the implications of who decides on involuntary treatment. PMID- 11201929 TI - Commentary: legal analysis of the Israel Psychiatric Association's proposal regarding compulsory hospitalization of the mentally Ill. PMID- 11201930 TI - The biopsychosocial model of medicine revisited: a meta-theoretical excursion. AB - Engel's biopsychosocial model of medicine has been widely endorsed by contemporary medicine, at least in theory. Yet, whereas Engel's notion refers mainly to physician-patient communication, the prevalent interpretation of this model is mainly etiological. The present meta-theoretical study examines the relation between the different notions of the model. Using logical analysis and the theory of (critical) rationality, in particular Wettersten's theory of (complementary) styles of rationality, it is argued that the different notions of the model may be complementary, rather than contradictory or incommensurable as usually implied by those holding them. PMID- 11201931 TI - Commentary: are there any inconsistencies among the notions of the biopsychosocial medical model? PMID- 11201932 TI - Oneiroid syndrome: a concept of use for western psychiatry. AB - Oneiroid syndrome (OS), or dream-like fantastic delusional derangement of consciousness, is characterized by a kaleidoscopic quality of psychopathological experiences, wherein reality, illusions and hallucinations are merged into one. It is typically accompanied by motor and, in particular, catatonic disturbances. This syndrome is an uncommon psychiatric state, which is hardly mentioned in standard psychiatric textbooks. OS is a neglected entity among DSM-oriented psychiatrists because it deals with a phenomenological approach in contrast to the European attitude, which deals with detailed clinical descriptions. Here, we propose detailed clinical descriptions with a number of consecutive stages of the OS development, illustrated by two vignettes with typical variants of oneiroid syndrome, in order to raise the awareness of psychiatrists who are not familiar with this state, and to try to open a window to the inner life of those patients suffering from this syndrome. These cases may also serve as illustration of certain principles which, when understood, may be found to lead in turn to a deeper knowledge of the psychopathology of other more commonplace conditions. PMID- 11201933 TI - Death foretold. AB - We briefly trace the history of a belief in the possibility that a person in apparent good health may accurately predict his or her own demise. The phenomenon is referred to as death foretold and we present presumed examples of it from the Bible, world literature, medical writings and newspaper reports without pretending to completeness. In two widely quoted scientific papers, death foretold is subsumed under the wider heading of decease due to psychic stress. We speculate on a possible link between the two, taking into consideration the fact that most people who prophesy their end are of an advanced age. PMID- 11201934 TI - Self-destructive behavior in adolescents who have not completed a process of mourning: case study. AB - The article deals with the problem of self-destructive behavior in adolescence through the perspective of family dynamics. Two vignettes describe an uncompleted process of mourning after the loss of a parent in two suicidal adolescents, a girl and a boy. It shows that suicidal behavior may be only a part of a long lasting process which is not always recognized. In both cases dysfunctional family relations did not allow the adolescents to deal properly with their feelings of responsibility, guilt and accumulated inner tension. Characteristic differences are shown between the girl, who is depressed and manifests somatoform disorder and regressive behavior, and the boy, whose unresolved conflicts and anxiety are manifested by conduct disorder. PMID- 11201935 TI - The wandering psychiatric emergency room--design, location and transformations. AB - We describe the changes in location and philosophy of a psychiatric emergency room over a period of 20 years. Four phases are described in which location, size, modes of access as well as internal and external boundaries reflect philosophies of treatment and the evolving identity of a psychiatric emergency room. The four phases include an early embryonic stage, a second stage involving rapid development of services, a third stage involving regression and consolidation and a fourth stage representing a fully developed independent service. The authors stress both external and rational considerations, such as mental health policies and budget, as well as unconscious irrational processes, which reflect the dynamic forces within the organization. PMID- 11201936 TI - An open trial of plant-source derived phosphatydilserine for treatment of age related cognitive decline. AB - We assessed whether the efficacy of plant-source derived phosphatydilserine (one of the phospholipids which play an important functional role in membrane-related processes in the brain) for treatment of age related cognitive decline is consistent with previous (placebo controlled) positive findings with bovine derivative of PS (BC-PS). Eighteen healthy elderly volunteers meeting Age Associated Memory Impairment inclusion and exclusion criteria were treated for 12 weeks with plant-source derived phosphatydilserine (PS) (100 mg x 3/day p.o.) and evaluated at base line, after 6 weeks of treatment and at the end of the trial. Fifteen concluded the study. All but two outcome measures elicited a significant drug over time effect. Post-hoc paired t-tests showed that the significant effect was attributable to an improvement from base line to week 6 and that effect was maintained at week 12. These results are encouraging. However, they await double blind controlled verification in a large sample before suggesting that this may be a viable approach to the treatment of age-related cognitive decline, without exposing the patients to possible hazards involved in the treatment with bovine derivative of PS (BC-PS). PMID- 11201937 TI - Attitudes toward homosexuality: an overview. AB - In the last decade it has become clear that impairment of the psychological well being of homosexuals has its origin in a society that discriminates and stigmatizes homosexuality. The article provides some basic information on homosexuality and continues with an overview of current knowledge on attitudes toward homosexuality. It gives special attention to the situation of homosexuality in Israel. Limited knowledge on the situation in Israel suggests that although there is an increase in tolerance toward homosexuality, it is not universally accepted and prejudice is common. PMID- 11201938 TI - The influence of information on social and occupational outcome in mental illness on the attitudes of students in Turkey. AB - BACKGROUND: In this article, we have tried to evaluate the influence of a series of determinants of stigmatization of mental illness. METHOD: 700 final year students of a University in Istanbul were asked to read one of 14 different hypothetical case stories. The stories contained different combinations of characteristics assumed to play a role in stigmatization. Each vignette was presented to 50 students. The stories were collected after five minutes and the following scales were completed: Characteristics Scale and Skill Assessment Scale. Analysis was conducted on each scale. RESULTS: We found a statistically significant difference among the groups given different hypothetical cases (vignettes). According to the post-hoc analysis, only the subjects given the vignette in which social and occupational outcome information were lacking showed statistically significant difference from the rest of the population. CONCLUSION: This study suggests that information on social and occupational outcome of mental illness influences the general perception of the mentally ill. PMID- 11201939 TI - Blaming parents in infant psychiatry. PMID- 11201940 TI - Xeroderma pigmentosum in three consecutive siblings of a Nigerian family: observations on oculocutaneous manifestations in black African children. PMID- 11201941 TI - Multifocal electroretinographic and angiographic changes in pre-eclampsia. PMID- 11201942 TI - Signet ring carcinoma of the eccrine sweat gland in the eyelid, treated by radiotherapy alone. PMID- 11201943 TI - Endonasal endoscopic dacryocystorhinostomy for dacryocystocoele in a 4 month old infant. PMID- 11201944 TI - Epstein-Barr virus associated acute retinal necrosis. PMID- 11201945 TI - Intrascleral recurrence of uveal melanoma after transretinal "endoresection". PMID- 11201946 TI - Leucocoria as the presenting sign of a ciliary body melanoma in a child. PMID- 11201947 TI - Spontaneous extrusion of subconjuctival cysticercus cellulosae. PMID- 11201948 TI - Massive basal cell carcinoma in a schizophrenic patient: treatment options and constraints. PMID- 11201949 TI - Spontaneous resolution of eyeball displacement caused by maxillary sinusitis. PMID- 11201950 TI - Familial thrombophilia and normal tension glaucoma. PMID- 11201951 TI - The wide field multifocal ERG reveals a retinal defect caused by vigabatrin toxicity. PMID- 11201952 TI - Retraction of published papers. PMID- 11201954 TI - Desktop research--bibliographic databases and electronic journals. . PMID- 11201955 TI - Prevalence of malocclusion and orthodontic treatment need in 10-year-old New Zealand children. AB - The need for orthodontic treatment was determined in a random sample of 10-year old Dunedin, New Zealand schoolchildren using the Dental Aesthetic Index (DAI); an index based on the social acceptability of dental appearance. When absent or unerupted teeth were disregarded, orthodontic treatment was considered to be "mandatory" for one-third of the children. The remaining children were almost equally divided into the three other treatment-need groups: "highly desirable", "elective", and "not necessary". The majority of the children had crowding and spacing in at least one incisor segment, and a molar occlusion other than Angle Class I. In this predominately mixed-dentition sample, more children were considered to need orthodontic treatment than older children in studies using the DAI. This raises some questions about the suitability of the DAI as a tool to assess orthodontic treatment need in mixed-dentition samples. PMID- 11201956 TI - An investigation of mandibular morphology in subjects with different vertical facial growth patterns. AB - In the present study, mandibular morphology was investigated on lateral cephalometric head films and dental casts of 60 subjects (30 females and 30 males) who had different vertical facial growth patterns. The sample had a mean age of 13.5 years, with a range of 11 to 15.5 years. The subjects were divided into three groups with regard to vertical facial growth by using the SN/GoGn angle to define low-angle, normal, and high-angle groups. In addition, each group was divided into two subgroups according to sex. The effects of the SN/GoGn angle and gender on mandibular morphology were investigated by means of analysis of variances. Tan Go, IMPA, SL, and EL measurements were found to be related to SN/GoGn, and the measurements of Go-Gn, Symphysis depth, and Intermolar width to be related to sex. PMID- 11201957 TI - Electropalatographic and cephalometric assessment of myofunctional therapy in open-bite subjects. AB - Myofunctional therapy (MFT) is often prescribed to correct tongue-thrust swallowing, with the expectation that anterior open bite (AOB) will reduce spontaneously if a more posterior tongue posture is learned. However, MFT has not been subjected to systematic evaluation. Electropalatography (EPG), which is used in speech pathology to measure dynamic tongue function for diagnostic, therapeutic and research purposes, is a suitable technique for the evaluation of MFT. This prospective clinical study assessed the effect of tongue re-education therapy on tongue function and dento-facial form in AOB patients. Electropalatography recordings of speech and swallowing, and lateral head cephalometric radiographs were obtained from eight 10-year-old boys with tongue thrust swallowing behavior and AOB before and after a course of tongue re education therapy. Although differences in cephalometric measurements before and after therapy were small, there was some evidence of a trend for upper and lower incisor eruption, with concomitant reduction of the AOB. Analysis of the EPG speech data was inconclusive, but the swallowing data showed trends for more consistent and more anterior patterns of EPG contact after therapy. Comparison of pre- and post-therapy EPG data with data from a parallel study using a group of age-matched controls indicated that some "normalisation" of swallowing behaviour had occurred. The results of this research imply that the therapy was partially successful in improving tongue function during swallowing and in reducing AOB. Further research on a larger sample over a longer observation period is required for more accurate assessment of soft and hard tissue changes. PMID- 11201958 TI - The duration of fixed orthodontic treatment: a comparison of two groups of patients treated using Edgewise brackets with 0.018" and 0.022" slots. AB - The duration of fixed appliance Edgewise orthodontic treatment times using brackets with 0.018" and 0.022" slots was measured to determine whether there were any clinically or statistically significant differences between the two appliances. Sixty-four consecutively treated, fully banded patients were selected from two different practice locations. All 64 patients were treated by one clinician. Thirty-two patients (Group 1) were treated using the 0.018" slot bracket and 32 (Group 2) were treated using the 0.022" slot bracket. The patients in each group were treated to the same standard of care using the same technique. The mean duration of treatment for Group 1 was 20.2 months and for Group 2, 21.7 months. Although the mean difference (1.5 months) was not clinically significant, it was statistically significant at p < 0.05. PMID- 11201959 TI - Dental changes and space gained as a result of early treatment of pseudo-Class III malocclusion. AB - This study was designed to investigate the dental changes and the space gained following early treatment of pseudo-Class III malocclusion, using a simple fixed appliance. Twenty-one consecutively treated patients who had a pseudo-Class III malocclusion comprised the treated group. Fifteen untreated control subjects were used as matched controls for the three-year follow-up after completion of treatment. Lateral cephalograms and study models were analysed for the treated, the control and the follow-up group. The arithmetic mean and standard deviation were calculated for each variable, and paired t-tests were performed to assess the effects of treatment on the treated group. The Mann-Whitney test was performed to evaluate the difference between the follow-up group and the control group. Anterior crossbites and mandibular displacements were eliminated after the treatment. On average, the space gained as a result of the treatment was 4.7 mm in the upper arch (p < 0.001 degree). Comparison of the space available as a result of early treatment with the space required for alignment of posterior segments in the upper arch of the untreated control group indicated that there was enough space for the eruption of the canines and premolars as a result of early treatment; whereas, lack of space was evident in the untreated controls. In conclusion, a pseudo-Class III malocclusion, proclination of the upper incisors and/or retroclination of the lower incisors contributed to the correction of anterior crossbite and the elimination of mandibular displacement. Proclination of the upper incisors, utilisation of leeway space, and arch-width increase provided the space required for eruption of the premolars and canines. PMID- 11201960 TI - Non-extraction treatment of a thirteen-year-old boy with a Class III skeletal discrepancy and severe crowding in both the upper and lower dentitions. AB - A thirteen-year-old boy presented with a Class III skeletal tendency in association with severe crowding in both the upper and lower arches. Whilst there was not a frank posterior crossbite, it was felt that the upper arch was narrow and that the lower arch was similarly constricted. Taking this into account along with the fact that his upper lip was flat and the nasolabial angle obtuse, it was decided to pursue a non-extraction treatment, with the aim of providing by expansion an extra 16 mm of space in the upper arch and 8 mm in the lower arch to accommodate the full dentition, and with a view to extracting third molar teeth later. This proved to be successful, albeit over an extended period of time, with active treatment taking nearly three and a half years. A realistic alternative would have been to remove four bicuspid teeth and pursue an orthodontic/surgical approach to treatment. In retrospect, and with the benefit of reviewing his records without surgical intervention, the treatment plan decided upon has been well justified. PMID- 11201961 TI - Finishing occlusion, degree of stability and the PAR index. AB - The occlusions of sixty-five patients, treated by one private specialist orthodontist with consistent philosophy and goals, were assessed according to the PAR Index. For each patient, pre-treatment, post-treatment and follow-up study models were assessed. Follow-up models were taken at least 6.5 years following the removal of all retention appliances. Mean-weighted PAR scores were calculated for the total sample and various sub-groups at each stage. Mean percentage changes in weighted PAR scores were also calculated. The relationships between the occlusal standards at the end of active treatment and at the end of the follow-up period, and specific diagnostic and treatment factors were then investigated to search for any factors that might be predictive of long-term post treatment occlusal stability or instability. The overall mean-weighted pre treatment, post-treatment and follow-up PAR scores were 25.5, 3.0 and 7.0, respectively. There was an 85.6 per cent decrease with treatment in the overall mean-weighted PAR score. This was followed by a 15.2 per cent increase in that overall mean during the follow-up period. In this introductory study, neither the PAR score at the end of active treatment, nor the amounts of occlusal change occurring during or after active treatment, were found to be predictive of the amount of post-treatment occlusal change. PMID- 11201963 TI - Treatment of a severe Class III skeletal discrepancy at an appropriate age. AB - The 13-year-old female patient presented for correction of a severe Class III malocclusion with a Class III skeletal pattern. This was considered an appropriate age for treatment as earlier treatment may have been subject to relapse because significant facial growth may have occurred after treatment, and because treatment at a later age may have required orthognathic surgery. Initially, maxillary expansion was provided to widen the maxilla and to free the circum-maxillary sutures. Maxillary protraction headgear was worn to perform sagittal skeletal improvement. Fixed orthodontic appliances were placed to align the dentition and Class III elastics were used to improve intercuspation and stability. Patient cooperation was crucial for success. The skeletal changes provided rewards that included significantly improved facial and dental appearance, while avoiding orthognathic surgery. PMID- 11201962 TI - Treatment of an "ankylosed" upper central incisor in the mixed dentition. AB - A ten-year-old boy presented with an unerupted upper right central incisor (UR1). An OPG radiograph showed a supernumerary tooth lying over its crown, preventing its eruption. Standard orthodontic treatment involving removal of the supernumerary tooth, attaching a gold chain to the UR1 and treatment with fixed orthodontic appliances failed to bring the tooth down, until it was found that tough fibrous gingival tissue entwined in the gold chain had "ankylosed" the tooth. Once this tissue had been removed and the wound packed open, the tooth was brought down successfully into occlusion. PMID- 11201964 TI - A comparison of retention rates of brackets with thermally-cured and light-cured custom bases in indirect bonding procedures. AB - This study compared the retention rates of thermally-cured (TC) and light-cured (LC) custom bases attached to metal mini-diamond brackets and clear Spirit MB brackets, when used in indirect bonding procedures. The custom base comprised either the light-cured or thermally-cured material attached to the bracket base and prepared in the laboratory, the whole unit later being bonded to the natural teeth. Thirty consecutively treated patients had fixed appliances fitted in both arches, with Spirit MB brackets on the maxillary anterior teeth, and metal brackets on the maxillary posterior and all mandibular teeth. All brackets were bonded using either the LC or TC method. All procedures and treatment was by the same operator, using identical techniques. Observation was for six months. All bonding failures were recorded. The results indicated no significant differences in the retention rates of either of the custom-base materials when used with metal brackets. However, the Spirit MB brackets exhibited a significantly higher bonding failure rate when a TC custom base was used. It was therefore concluded that either material could be used in the indirect bonding of metal brackets, and that LC custom bases should be used in the indirect bonding of Spirit MB brackets. PMID- 11201965 TI - International Journal Editors' Symposium. PMID- 11201966 TI - The immunohistochemical response of the rat periodontal ligament endothelium to an inflammatory stimulus. AB - Recently, inflammation has been recognised as an important co-requisite to orthodontic tooth movement. When such a reaction is initiated, the process of up regulation of certain adhesion molecules may occur, resulting in the extravasation of leukocytes. This may stimulate progenitor/precursor pathways and signals that regulate the biological responses resulting in tooth movement. We propose that up-regulation of leukocyte adhesion molecules occurs in response to orthodontic forces, resulting in circulating monocyte attraction, extravasation and differentiation into osteoclasts, which are responsible for bone resorption that results in orthodontic tooth movement. To investigate this hypothesis, it is necessary to determine whether periodontal ligament (PDL) endothelium responds to inflammatory stimuli as other organs do. We studied the normal distribution of endothelial adhesion molecule ICAM-1 within PDL vessels, and then the following exposure to an inflammatory endotoxin. The rat PDL blood vessels expressed ICAM-1 in response to the inflammatory stimulus, similar to other organs, suggesting that the inflammatory responses are similar. Whether and where in the PDL microvascular bed orthodontic forces cause up-regulation of ICAM-1 needs to be established. PMID- 11201967 TI - Anterior open-bite malocclusion: stability of maxillary repositioning using rigid internal fixation. AB - A retrospective cephalometric study was performed to investigate the stability of 37 non-growing anterior open-bite cases using mini-plate rigid fixation. The sample was divided into two groups: Group A: maxillary repositioning alone (17 cases) and Group B: bimaxillary surgery (20 cases). Tracings were performed pre operatively (T1), immediately post-operatively (T2) and at a minimum of one year follow-up (T3) (12-90 months). In Group A, the maxilla was advanced (3.8 +/- 2.8 mm, p < 0.01) and superiorly repositioned at PNS (2.8 +/- 2.3 mm, p < 0.001). In Group B, the maxilla was advanced (3.5 +/- 3.0 mm, p < 0.01) and superiorly repositioned at PNS (3.7 +/- 1.8 mm, p < 0.001); and the mandible (11.7 +/- 3.8 mm, p < 0.001), with no significant change in the vertical plane (p > 0.05). Late relapse due to condylar remodelling or resorption was found as a cause of large horizontal relapse (8.0 < x < 14.0 mm) in three cases (15%), the amount being associated with the amount of operative advancement (r = 0.7, r-sq = 40%, p < 0.01). It was concluded that the correction of anterior open bite by posterior repositioning of the maxilla using rigid fixation is a stable procedure during the follow-up period, and that in bimaxillary cases, post-operative stability depends largely on the stability of the mandibular advancement, which in turn relates to the amounts of advancement, the pre-operative anterior open bite and the mandibular plane angle. PMID- 11201968 TI - A comparison of two methods of assessing orthodontic treatment need in the mixed dentition: DAI and IOTN. AB - This paper assesses the unmet orthodontic treatment need in a random sample of 10 year-old schoolchildren, using two indices: the Dental Aesthetic Index (DAI) and the Index of Orthodontic Treatment Need (IOTN). The DAI scores were adjusted by omitting the missing teeth component of the index because many children were in the mixed dentition with unerupted permanent teeth. Although both indices assessed the same number of children with malocclusions requiring orthodontic treatment, not all were ranked similarly by each index. PMID- 11201970 TI - Effectiveness and duration of two-arch fixed appliance treatment. AB - The aims of this study were to determine the effectiveness and duration of single phase two-arch fixed appliance treatment and to evaluate factors that may influence these two variables. Data were collected from 177 consecutively completed cases at the Orthodontic Department, Government Dental Clinic, Singapore, during a three-month period. Pre-treatment and post-treatment models were assessed using the Peer Assessment Rating (PAR) index. The result showed that two-arch fixed appliance treatment reduced the malocclusions on average by 77.80 per cent over a period of 25 months. Multiple regression techniques revealed that 22 per cent of the variability in treatment effectiveness could be explained by the pre-treatment PAR score, the age at the start of treatment, the frequency of office visits and whether or not the treatment involved extractions. The variation in treatment duration was due to the frequency of office visits, the pre-treatment PAR score and whether or not the treatment involved extractions or headgear. PMID- 11201969 TI - Ultrastructural identification of cells involved in the healing of intramembranous bone grafts in both the presence and absence of demineralised intramembranous bone matrix. AB - Alveolar bone defects are conditions that impede the progress of orthodontic treatment. This study compared the mechanics of the healing of autogenous intramembranous (IM) bone grafts and grafts comprising a mixture of IM and demineralised bone matrix of autogenous intramembranous origin (DBMIM), in an attempt to determine the reliability of each material. Thirty-two New Zealand white rabbits had a single defect created in their skull. Sixteen were grafted with IM bone alone (Group I: autogenous IM), and the other 16 had a combined graft of composite IM sandwiched between two layers of DBMIM (Group II: composite IM-DBMIM). A third group (Group III) of eight rabbits each had two defects created in their skull; one defect was left empty (A: passive control) and the other filled with rabbit-skin collagen (B: active control). In Groups I and II, inflammatory cells were found to be present on Days 1 and 2 of tissue retrieval. The appearance of the mesenchymal cells and preosteoblasts, osteoblasts and osteocytes was earlier (Day 3) in Group II than in Group I (Day 5). In both groups, preosteoblasts, osteoblasts and osteocytes were observed with no cartilage at the intermediate stage. In conclusion, autogenous IM bone grafts and IM bone grafts in the presence of DBMIM healed through an osteogenic ossification route. PMID- 11201971 TI - In re: Di Chiro G, Schellinger D. Computed tomography of spinal cord after lumbar intrathecal introduction of metrizamide (computer assisted myelography). PMID- 11201972 TI - Absence of selective deep white matter ischemia in chronic carotid disease. PMID- 11201973 TI - [Benzodiazepines and pregnancy]. AB - The use of benzodiazepines is not negligible in pregnant woman and self medication is considerable. To investigate the effects on the fetus of benzodiazepines used during pregnancy, we reviewed animal and clinical studies completed with observations of CRPV (Centres Regionaux de Pharmacovigilance). Pooled results indicate that the risk of malformations associated with first trimester exposure to benzodiazepines remains small. However, in a fetus exposed essentially to long-acting benzodiazepines on a long-term basis, neonatal hypotonicity, failure to feed and/or withdrawal syndrom could be observed. PMID- 11201974 TI - [Susceptibility of the elderly patient to hyponatremia induced by selective serotonin reuptake inhibitors]. AB - Numerous spontaneous reports of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) have followed the increased use of selective serotonin reuptake inhibitors (SSRI). It has been estimated that 1 in 200 patients treated per year developed SIADH, age and low body weight being particular risk factors. No clear gender effect has been detected when confounding factors such as body weight or antidepressant consumption are taken into account. Age-related susceptibility to hyponatraemia may be explained by physiological changes in renal and endocrine function. The high prevalence of polymedication and pluripathology in the elderly may be a contributing factor as well. To date, no study has demonstrated how SSRIs affect the regulation of fluid/sodium balance nor whether they have an independent effect on this regulation in depressed subjects. PMID- 11201975 TI - [Drug prescription for pregnant women in the department of the Loire] . AB - A prospective drug prescription and descriptive study was undertaken in a sample of 214 pregnant women in the department of the Loire. This population was randomized using pregnancy declaration files from the French Health Care Centre. Data recording was retrospective. A total of 2064 drugs have been prescribed; 90 per cent of women received at least one drug during the course of pregnancy with an average of 11.5 drugs per woman. Antispasmodics are mainly prescribed in the first trimester while vitamins, mineral supplements, antianemics and vasoactive agents are found in the third trimester. Prescriptions do not rise with age but increase in urban areas. Use of PDD/DDD (Prescribed Daily Dose/Defined Daily Dose) is an estimation of prescription customs. For ketoprofen, it is 1.6 in the last trimester, although this drug is contra-indicated. PMID- 11201976 TI - [Midodrine (Gutron) prescription practice at a University Hospital Center]. AB - A historical study of the prescription of midodrine was carried out at the university hospital of Toulouse (France) between 1994 and 1998. The aim was to compare the observed prescriptions and the ideal prescriptions in accordance with the Summary of Product Characteristics (SPC). The analysis of 97 consecutive medical reports found discrepancies in prescription concerning the non-respect of contraindications and of potentially hazardous drug associations. Fifty-four (55.7 per cent) patients would have been excluded from prescription if the physicians had strictly respected the SPC. The inappropriate prescription of midodrine was associated with an increase in adverse drug reactions (ADRs). ADRs occurred in 34.0 per cent of cases overall and required drug discontinuation in 15.5 per cent. PMID- 11201977 TI - Caffeine metabolism differences in acute hepatitis of viral and drug origin. AB - The 24-h urinary excretion rate of caffeine metabolites following 200 mg caffeine intake has been proved to be a valuable safe quantitative test of liver function. The pathological mechanism of acute hepatitis of viral and drug origin is different. In both diseases, the patient's caffeine metabolic capacity during the acute and the recovery period was compared. In the acute period, in both diseases, the strongly reduced metabolism of caffeine paralleled the variations of the usual biochemical tests. During the recovery period, in viral hepatitis, caffeine metabolism and biochemical tests returned to the normal values. In drug induced hepatitis during the recovery period, caffeine metabolism remained severely impaired at a time when biochemical tests were back to the control levels. This discrepancy might be due to the histological or molecular toxic effects of the drug(s), irrespective of cytolysis. After drug-induced hepatitis, a caffeine test might be used to check the total recovery or to choose an adapted dosage of medicines. PMID- 11201978 TI - [Dementia and extrapyramidal problems caused by long-term valproic acid]. AB - Among the side-effects attributed to valproic acid (VPA), the occurrence of Parkinsonian syndromes and cognitive impairment is very uncommonly reported. We describe five cases of reversible associated Parkinsonism. These cases were observed in epileptic patients, 57 to 74 years old, two women and three men. Extrapyramidal disorders appeared after various durations of treatment (from 6 months to 10 years). Dementia characterized by an insidious onset was associated in three cases and bradypsychia in one case. Brain pseudoatrophy was present in three patients. In all cases the signs and symptoms improved some weeks or months after discontinuation of VPA. In the literature some cases, usually in young adults or children, have been reported. In a prospective study, Armon et al. found various abnormal symptoms and signs related to motor and cognitive function impairment in patients with long-term VPA therapy. These side-effects may be related to a disturbance in the gabaergic pathways in the basal ganglia system. It is of interest to consider that delta 2-valproic acid, a metabolite of VPA, is especially accumulated in selected areas of the brain: the substantia nigra, superior and inferior colliculus, hippocampus and medulla. PMID- 11201979 TI - [Adverse effects of anticancer drugs: apropos of a pharmacovigilance study at a specialized oncology institution]. AB - We investigated the frequency of ADRs occurring during one year (1995) in a French regional cancer institute. Patients with at least one ADR leading to or occurring during hospitalization in the institute were identified by searching diagnosis codes potentially related to an adverse drug reaction in the hospital medical database of the PMSI (Programme de medicalisation des Systemes d'Information). We found 435 hospitalizations relative to 285 patients (6.2 per cent of the whole population of inpatients in 1995 and 3.1 per cent of stays in 1995). The total cost to treat ADRs was 1.7 per cent of the total budget of the hospital with a median cost of 8517 francs (mean cost: 13,271 +/- 15,330 francs). The highest cost was due to medical staff, blood transfusions, and anti infectious drugs, despite the use of prophylactic agents. These results emphasize the high incidence and excess costs of ADRs related to anticancer chemotherapy. PMID- 11201980 TI - [Attitude of the clinican toward adverse effects of protease inhibitors]. AB - Since 1996, marketing of new drugs called protease inhibitors has revolutionized the treatment of patients suffering from AIDS. The side-effects of this new therapeutic family are quite well known but we wanted to evaluate the attitude of the clinician: can these adverse effects be corrected by symptomatic treatment, do they regress spontaneously or do they lead to an alternative PI therapy? We therefore carried out a retrospective survey in the Infectious Diseases Department of Poitiers Hospital consisting in research on files of patients (n = 70) treated in this department (hospitalization and consultation) for any clinical or biological abnormality attributable to the PI. For each drug we determined what sort of side-effects could be found and the position adopted by the clinician. For 30 patients the PI was stopped and for 21 of these cases because of drug toxicity (gastrointestinal, neurological, renal and metabolic effects). The biological anomalies are quite well tolerated and regress spontaneously in most cases. PMID- 11201981 TI - [Interstitial nephropathy with intracellular pigment deposits and chronic bisacodyl abuse]. PMID- 11201982 TI - Inappropriate antidiuretic hormone secretion and rhabdomyolysis associated with citalopram. PMID- 11201983 TI - [Arthralgia associated with mirtazapine]. PMID- 11201984 TI - Mirtazapine and restless leg syndrome: a case report. PMID- 11201985 TI - Evaluation of vascular injury with proinflammatory cytokines, thrombomodulin and fibronectin in patients with primary fibromyalgia. AB - OBJECTIVE: Cold intolerance, cold induced peripheral vasospasm, Raynaud's phenomenon, livedo reticularis and immunoglobulin deposition in the skin are often encountered clinical and laboratory findings in patients with primary fibromyalgia (FM). These findings are suggestive of vascular injury. METHODS: Eighty patients (4 male, 76 female) with fulfilling primary FM criteria (FM (+) patient group), 60 patients (3 male, 57 female) with chronic musculoskeletal complaints but without FM (FM (-) patient control group) and 40 healthy volunteers (1 male, 39 female) without musculoskeletal complaints (healthy control group) were enrolled in this cross-sectional study. The study was carried out in two steps. In the first step, the clinical findings, routine laboratory tests, autoantibodies and radiological findings were investigated. The second step were consisted of the laboratory investigations of thrombomodulin and fibronectin as the mediators indicating vascular injury and proinflammatory cytokines in FM patients with Raynaud's phenomenon and/or livedo reticularis and in control groups. RESULTS: There were no differences between study and control groups with regard to laboratory, radiological and immunological (ANA, AntidsDNA, ENA, anticardiolipin IgG and IgM) results. No statistically significant differences were found in the levels of proinflammatory cytokines between FM (+) patient group and control groups (p > 0.05). Thrombomodulin was also shown statistically insignificant difference between FM (+) patient group and control groups (p > 0.05). However, fibronectin, another mediator of vascular injury, was higher in FM (+) patient group and the differences between FM (+) patients and each control groups were statistically significant (p < 0.0001). CONCLUSION: Our results were suggestive of the presence of a non-immunological vascular injury in FM patients with Raynaud's phenomenon and/or livedo reticularis. PMID- 11201986 TI - Severe disseminated BCG infection in an 8-year-old girl. AB - An 8-year-old girl died of sepsis due to staphylococcal infection one year and 8 months after Bacille Calmette-Guerin (BCG) revaccination. Two months after the vaccination in accordance with the school health program, she was hospitalized with a high fever, skin rash over the face and lower limbs, and leukopenia. Her clinical and laboratory pictures were not compatible with those of any established type of immunodeficiency. The polymerase chain reaction (PCR) test for M. tuberculosis complex was positive for bone marrow, pleural fluid, and peripheral blood. The strain recovered from a mycobacterial culture of the blood was identical to the BCG strains with which the patient was vaccinated, based on restriction fragment length polymorphism (RFLP) and a pulse-field gel electrophoresis (PFGE) analyses of DNA. She developed finally a lung abscess due to staphylococcal septicemia, which was the direct cause of her death. PMID- 11201987 TI - Combined effect of docetaxel and cisplatin for non-small cell lung cancer cell lines in vitro. AB - Docetaxel (DOC) plus cisplatin (CDDP) is a novel combination chemotherapy for the treatment of advanced non-small-cell lung cancer (NSCLC). We investigated the combined effect of DOC with CDDP in sequence and the reverse schedule for NSCLC cell lines EBC-1 (squamous cell carcinoma) and RERF-LC-MS (adenocarcinoma) using an MTT assay and an improved isobologram method. The results showed that the combination of DOC and CDDP in human lung cancer cell lines was antagonistic. To investigate the possible mechanism of the antagonistic effect, we focused on the cell cycle perturbation and the inhibition of apoptosis fractions induced by chemotherapeutic agents. Pretreatment of CDDP significantly blocked the following DOC-induced apoptosis fraction. Therefore we consider that the suppression of apoptosis could be one of the mechanisms for antagonistic effects of combination chemotherapy of DOC and CDDP. PMID- 11201988 TI - Contact dermatitis. PMID- 11201989 TI - Pathogenesis and the role of Ca2+ overload during myocardial ischemia/reperfusion. AB - To study the regulation of [Na+]i and [Ca2+]i during myocardial ischemia/reperfusion, [Na+]i and [Ca2+]i were measured simultaneously using guinea pig ventricular myocytes which were dual-loaded with SBFI/AM and fluo 3/AM. It was suggested that: (1) [Na+]i increased during metabolic inhibition (MI: 3.3 mM amytal and 5 microM CCCP) by both the activated Na+ influx via Na+/H+ exchange and the suppressed Na+ extrusion via the Na+/K+ pump; (2) Na+/Ca2+ exchange was inhibited during MI, causing the dissociation between [Na+]i and [Ca2+]i; (3) Na+/Ca2+ exchange could be reactivated by energy repletion, resulting in a significant increase in [Ca2+], Furthermore, a Ca2+ influx via the reverse-mode of Na+/Ca2+ exchange may play a key role in the mechanism of Ca2+ overload on reoxygenation; and (4) cell contracture during MI was related to rigor due to energy depletion, while cell contracture after energy repletion was likely to be related to Ca2+ overload. PMID- 11201990 TI - Characterization of the human DNA polymerase delta catalytic subunit expressed by a recombinant baculovirus. AB - The catalytic subunit of human DNA polymerase (pol) delta, p125, was expressed in recombinant baculovirus-infected insect cells, separated from a baculovirus encoded DNA polymerase, and was purified to homogeneity by affinity trapping with a histidine-octapeptide at the C-terminus of p125 as the ligand. Purified p125 showed DNA polymerase activity resembling conventionally purified calf thymus pol delta. However, the two differed in four ways: 1) the specific activity of recombinant p125 was one quarter of the calf thymus pol delta; 2) the recombinant p125 was relatively resistant to aphidicolin; 3) the apparent Km for dTTP of the recombinant p125 was estimated at 33 microM, 15-fold the value for calf thymus pol delta; and 4) the recombinant p125 was not stimulated by recombinant PCNA, while activity of calf thymus pol delta increased 150-fold in response. Furthermore, PCNA did not stimulate either the p125 incubated with p50, a small subunit of pol delta, or co-expressed with p50 in insect cells. The full length recombinant p125 migrated slightly faster than pol delta from human cell lines, Jurkat or HeLa, upon SDS-polyacrylamide gel electrophoresis, suggesting a post translational modification. The results indicate that in vivo assembly of the fully active complex of pol delta requires factors in addition to p125 and p50 subunits, and/or a post-translational modification of p125. PMID- 11201991 TI - Fatty acid analysis of blood plasma of patients with Alzheimer's disease, other types of dementia, and cognitive impairment. AB - Fatty acid differences, including docosahexaenoic acid (DHA; 22:6n-3) have been shown in the brains of Alzheimer's patients (AD) as compared with normal age matched individuals. Furthermore, low serum DHA is a significant risk factor for the development of AD. The relative concentration of DHA and other fatty acids, however, in the plasma of AD patients compared with patients with other kinds of dementias (other dementias; OD), patients who are cognitively impaired but nondemented (CIND), or normal patients is not known. In this study we analyzed the total phospholipid, phosphatidylcholine (PC), phosphatidylethanolamine (PE), and lysophosphatidylcholine (lysoPC) fractions of plasma from patients diagnosed with AD, OD, or CIND and compared them with a group of elderly control subjects with normal cognitive functioning. Plasma phospholipid and PC levels of 20:5n-3, DHA, total n-3 fatty acids, and the n-3/n-6 ratio were lower in the AD, OD, and CIND groups. Plasma phospholipid 24:0 was lower in the AD, OD, and CIND groups as compared with the group of control patients, and total n-6 fatty acid levels were higher in the AD and CIND groups only. In the plasma PE fraction, levels of 20:5n 3, DHA, and the total n-3 fatty acid levels were significantly lower in the AD, OD, and CIND groups. DHA levels were lower in the lysoPC fraction of CIND individuals only. There were no other differences in the fatty acid compositions of the different phospholipid fractions. Therefore, in AD, OD, and CIND individuals, low levels of n-3 fatty acids in the plasma may be a risk factor for cognitive impairment and/or dementia. Interestingly, a decreased level of plasma DHA was not limited to the AD patients but appears to be common in cognitive impairment with aging. PMID- 11201992 TI - In vivo evaluation of the effects of continuous exercise on skeletal muscle triglycerides in trained humans. AB - Magnetic resonance spectroscopy (1H MRS) and imaging (MRI) were used to investigate the effects of a bout of moderate prolonged exercise on intra (IMCL)- and extramyocellular lipid (EMCL) utilization in the soleus, tibialis anterior, and gastrocnemius muscles of five trained human subjects. MRI and 1H MRS measurements were obtained before and after a 90 min run on a calibrated treadmill at a velocity corresponding to 64 +/- 1.5% of each subjects' maximal rate of oxygen consumption. There were significant decreases in IMCL following exercise in the tibialis (pre: 22.37 +/- 4.33 vs. post: 15.16 +/- 3.25 mmol/kg dry wt; P < 0.01) and soleus (pre: 36.93 +/- 1.45 vs. post: 29.85 +/- 2.44 mmol/kg dry wt; P < 0.01) muscles. There was also a decrease in the gastrocnemius muscle, although this did not reach the level of significance (pre: 33.78 +/- 5.35 vs. post: 28.48 +/- 5.44 mmol/kg dry weight; P < 0.10). No significant changes were observed in EMCL or subcutaneous fat. In conclusion, this study showed that IMCL were significantly utilized in the tibialis and soleus muscles of aerobically endurance-trained humans. The absence of significant utilization of IMCL in the gastrocnemius may reflect differences in fiber type and/or intensity of contraction for each muscle group. PMID- 11201993 TI - Linoleic acid metabolism in the spontaneously diabetic rat: delta6-desaturase activity vs. product/precursor ratios. AB - The activity of delta6-desaturase of linoleic acid, a rate-limiting step in the formation of arachidonic acid, is decreased in animal models of severe, uncontrolled diabetes. The aim of the study was to measure the activity of liver microsomal delta6-desaturase of spontaneously diabetic BioBreeding/Edinburgh rats receiving subcutaneous insulin daily and of genetically related nondiabetic animals. The activity of delta6-desaturase was then compared with indices of activity (plasma lipid fatty acid product/precursor ratios) frequently used in human studies. Diabetic rats treated with insulin had 75 +/- 8% of the activity of microsomal delta6-desaturase of nondiabetic controls (P < 0.05). Insulin withdrawal tended to reduce the activity further (61% of control), although the activity did not differ from insulin-treated diabetic rats. The ratio of plasma phospholipid or cholesteryl ester gamma-linolenic over linoleic acid was not decreased in insulin-treated diabetic rats. By contrast, the ratio of gamma linolenic over linoleic acid of microsomes was almost three-fold higher in insulin-treated diabetic rats (P < 0.05). The gamma-linolenic over linoleic acid ratio as an index of activity gave inconsistent results in insulin-deprived rats. The ratio of gamma-linolenic over linoleic acid of cholesteryl esters did not differ between control and diabetic rats, nor did it correlate with microsomal delta6-desaturase activity. Furthermore, the index of delta6-desaturase activity, derived from the fatty acid composition of microsomal phospholipids, did not correlate with microsomal delta6-desaturase activity. Diabetes, even when controlled by regular insulin injections, reduces the metabolism of linoleic acid, but the effect is less than previously published. The fatty acid compositions of plasma and liver microsomal lipids are not reliable indices of delta6-desaturase activity in diabetes. PMID- 11201994 TI - Hepatic microsomal and peroxisomal docosahexaenoate biosynthesis during piglet development. AB - The roles of peroxisomes and microsomes on the biosynthetic pathway for docosahexaenoic acid (DHA) from alpha-linolenic acid (ALA) were investigated. Microsomes and peroxisomes were prepared from livers of fetal and neonatal piglets by a combination of differential and gradient layer centrifugation. Microsomes, peroxisomes, and combined cell fractions were incubated with [13C U]18:3n-3. The [M] and [M + 18] isotopomers of the fatty acids in the long-chain polyunsaturated fatty acid (LCPUFA) n-3 pathway were detected by gas chromatography-mass spectrometry. The quantity of each fatty acid was determined by gas chromatography, and synthesis of each fatty acid was calculated for a 30 min period. Synthesis of DHA was not detected in combined fetal liver fractions. The data suggest that DHA in the fetus is probably supplied from maternal sources through the placenta. In either singly incubated microsomal or peroxisomal preparations from neonatal livers, no DHA synthesis was detected. After combination of the microsomal and peroxisomal fractions, DHA synthesis was evident and increased rapidly between birth and 2 wk of age. This is the first demonstration of the entire biosynthetic LCPUFA n-3 pathway in subcellular organelles starting from isotopically labeled ALA to the final product, DHA, with all the intermediates present and isotopically labeled. The primary importance of the data is that it unequivocally demonstrates that peroxisomes are required for biosynthesis of DHA from ALA. PMID- 11201995 TI - Dietary cholesterol induces changes in molecular species of hepatic microsomal phosphatidylcholine. AB - After 21 days on a diet containing 1 g% cholesterol and 0.5 g% cholic acid, rats had an increased content of cholesterol in liver microsomal lipids. In liver, both cholesterol content and delta9 desaturase activity increased, whereas delta6 and delta5 desaturase activities decreased. These changes correlated with increases in oleic, palmitoleic, and linoleic acids and decreases in arachidonic and docosahexenoic acids in total microsomal lipids. Similar fatty acid changes were found in phosphatidylcholine (PC), the principal lipid of the microsomal membrane. In PC the predominant molecular fatty acid species (67% of the total) in the control rats were 18:0/20:4, 16:0/20:4, and 16:0/18:2; and they mainly determined the contribution of PC to the biophysical and biochemical properties of the phospholipid bilayer. The cholesterol diet decreased specifically the 18:0/20:4 species, and to a lesser extent, 16:0/20:4 and 18:0/22:6. The 18:1 containing species, especially 18:1/18:2 and less so 16:0/18:1 and 18:1/20:4, were increased. A new 18:1/18:1 species appeared. The independent effects of the presence of cholesterol and change of the fatty acid composition of the phospholipid bilayer of liver microsomes on the packing were studied by fluorescence methods using 6-lauroyl-2,4-dimethylaminonaphthalene, 1,6-diphenyl 1,3,5-hexatriene and 1-(4-trimethylammonium phenyl)-6-phenyl-1,3,5-hexatriene, which test different parameters and depths of the bilayer. Data showed that the increase of cholesterol in the membrane, and not the change of the fatty acid composition of phospholipids, was the main determinant of the increased bulk packing of the bilayer. The increase of fluid oleic- and linoleic-containing species almost compensated for the drop in 20:4- and 22:6-containing molecules. But the most important effect was that the general drop in essential n-6 and n-3 polyunsaturated fatty acids meant that this endogenous source for the needs of the animal decreased. PMID- 11201997 TI - Kinetics of 2-monoacylglycerol acyl migration in model chylomicra. AB - In the metabolism of triacylglycerol (TG)-rich lipoproteins, 2-monoacylglycerols (2-MG) are produced by lipoprotein lipase (LPL) hydrolysis of TG. The metabolic fate of 2-MG is not known with certainty. 2-MG that accumulate on the chylomicra surface have been proposed to isomerize spontaneously to 1(3)-MG, which are then hydrolyzed by LPL to free fatty acids and glycerol. In this study the rate and the effect of acyl chain saturation on the spontaneous acyl migration of 2-MG in in vitro model chylomicra emulsions were determined. After 1 h of incubation at 37 degrees C, less than 20% of 2-monoolein (2-MO) or 2-monopalmitin (2-MP) spontaneously isomerized to 1(3)-MO or 1(3)-MP, respectively. Accordingly, it was concluded that spontaneous isomerization of 2-MG is not the major mechanism for 2 MG metabolism post-TG hydrolysis in chylomicra. Isomerization rates, expressed as decrease in percentage of 2-MG remaining per hour, were -5.12 and -5.86 in water, and -0.43 and -0.41 in hexane for 2-MO and 2-MP, respectively. There was no significant difference between the isomerization rates of 2-MO and 2-MP. Thus, in the present study, saturation of the MG acyl chain did not influence spontaneous acyl migration in either water or hexane, but isomerization of 2-MG was faster in water than in hexane. PMID- 11201996 TI - Effect of medium-chain fatty acid positional distribution in dietary triacylglycerol on lymphatic lipid transport and chylomicron composition in rats. AB - The present study was carried out to examine if the positional distribution of medium-chain fatty acid (MCF) in dietary synthetic fat influences lymphatic transport of dietary fat and the chemical composition of chylomicrons in rats with permanent cannulation of thoracic duct. Four types of synthetic triacylglycerol were prepared: (i) sn-1 (3) MCF-sn 2 linoleic acid, (ii) interesterified sn-1(3) MCF-sn 2 linoleic acid, (iii) sn-2 MCF-sn-1(3) linoleic acid, and (iv) interesterified sn-2 MCF-sn-1(3) linoleic acid. A purified diet composed of equal amounts of the synthetic fat and cocoa butter was given to rats with permanent lymph duct cannulation. The positional distribution of MCF in the dietary fat had no significant effect on the lymph flow, triacylglycerol output, phospholipid output, lipid composition of chylomicrons, or the particle size. The positional distribution of MCF in the synthetic triacylglycerol was maintained in the chylomicron triacylglycerol. These results showed that MCF in the dietary triacylglycerol is transported into lymphatics and the positional distribution is well preserved in chylomicron triacylglycerol. PMID- 11201998 TI - Purification, characterization, and molecular cloning of group I phospholipases A2 from the gills of the red sea bream, Pagrus major. AB - Phospholipase A2 (PLA2) activity was investigated in various tissues of male and female red sea bream. In both male and female fishes, the specific activity of PLA2 in the gills was 70 times higher than that in other tissues, such as the adipose tissue, intestine, and hepatopancreas. Therefore, we tried to purify PLA2 from the gill filaments of red sea bream to near homogeneity by sequential chromatography on Q-Sepharose Fast Flow, Butyl-Cellulofine, and DEAE-Sepharose Fast Flow columns, and by reversed-phase high-performance liquid chromatography. Two minor and one major PLA2, tentatively named G-1, G-2 and G-3 PLA2, were purified, and all showed a single band with an apparent molecular mass of approximately 15 kDa by sodium dodecylsulfate-polyacrylamide gel electrophoresis. The exact molecular mass values of G-1, G-2, and G-3 PLA2 were 14,040, 14,040 and 14,005 Da, respectively. G-1, G-2, and G-3 PLA2 had a Cys 11 and were all identical in N-terminal amino acid sequences from Ala-1 to Glu-56. A full-length cDNA encoding G-3 PLA2 was cloned by reverse transcriptase-polymerase chain reaction and rapid amplification of cDNA ends methods, and G-3 PLA2 was found to be classified to group IB PLA2 from the deduced amino acid sequence. G-1, G-2, and G-3 PLA2 had a pH optimum in an alkaline region at around pH 9-10 and required Ca2+ essentially for enzyme activity, using a mixed-micellar phosphatidylcholine substrate with sodium cholate. These results demonstrate that three group I PLA2, G-1, G-2, and G-3 PLA2, are expressed in the gill filaments of red sea bream. PMID- 11201999 TI - Unusual lipid composition of a Bacillus sp. isolated from Lake Pomorie in Bulgaria. AB - The lipid composition of a Bacillus sp., isolated from Lake Pomorie in Bulgaria, was unusual and consisted of 26 different fatty acids between C12 and C26, with anteiso C15-C17 saturated fatty acids predominating. The furan fatty acid, 10,13 epoxy-11-methyloctadeca-10,12-dienoic acid, was also identified, a new finding for this genus. The hydrocarbons consisted of 30 different monounsaturated hydrocarbons, between C25 and C30, with the iso-iso, iso-anteiso, anteiso anteiso, iso-normal, and anteiso-normal methyl branching for odd-numbered chains, and the iso-iso, iso-anteiso, iso-normal, and anteiso-normal methyl branching for even-numbered chains. The double bond positions in these hydrocarbons were determined by dimethyl disulfide derivatization followed by GC-MS, and the double bond cis configuration was confirmed by infrared spectroscopy. Some previously unknown hydrocarbons in bacteria, such as (Z)-3,21-dimethyl-9-tricosene, (Z)-3,21 dimethyl-10-tricosene, (Z)-2,24-dimethyl-11-pentacosene, and (Z)-2,25-dimethyl-13 hexacosene were identified. Sterols were detected and were based on the sitosterol nucleus. PMID- 11202000 TI - Electron microscopy may reveal structure of docosahexaenoic acid-rich oil within Schizochytrium sp. AB - Schizochytrium sp. is an algae-like microorganism utilized for commercial production of docosahexaenoic acid (DHA)-rich oil and dried microalgae for use as a source of DHA in foods, feeds, and nutritional supplements. Electron microscopic analysis of whole cells of Schizochytrium sp. employing sample preparation by high-pressure freeze substitution suggests the presence of secondary and tertiary semicrystalline structures of triacylglycerols within the oil bodies in Schizochytrium sp. A fine secondary structure consisting of alternating light- and dark-staining bands was observed inside the oil bodies. Dark bands were 29 +/- 1 A in width, and light bands were 22 +/- 1 A in width. The tertiary (three-dimensional) structure may be a multilayered ribbon-like structure which appears coiled and interlaced within the oil body. In freeze fracture photomicrographs, Schizochytrium oil bodies exhibited fracture planes with terraces averaging 52 +/- 7 A in height which could correspond to the combined width of two halves of two light bands and one dark band observed in the high-pressure freeze substitution photomicrographs. The results suggest that triacylglycerols within Schizochytrium sp. oil bodies may be organized in a triple chain-length structure. High-pressure freeze substitution electron micrographs of two other highly unsaturated oil-producing species of microalgae, Thraustochytrium sp. and Isochrysis galbana, also revealed this fine structure, whereas microalgae containing a higher proportion of saturated oil did not. The results suggest that the staining pattern is not an artifact of preparation and that the triple chain-length conformation of triacylglycerols in Schizochytrium sp. oil bodies may be caused by the unique fatty acid composition of the triacylglycerols. PMID- 11202001 TI - Lipid class composition of the protozoan Perkinsus marinus, an oyster parasite, and its metabolism of a fluorescent phosphatidylcholine analog. AB - Perkinsus marinus is one of two important protozoan parasites of the eastern oyster, Crassostrea virginica. The other is Haplosporidium nelsoni. Lipids extracted from 7-d-old in vitro cultured P. marinus meronts, incubated with fluorescent-labeled phosphatidylcholine (FL PC) and nonincubated P. marinus meronts, were analyzed by a high-performance liquid chromatography (HPLC) system equipped with a diol phase column, in combination with thin-layer chromatography coupled with a flame-ionization detector (TLC/FID), and high-performance thin layer chromatography (HPTLC). Various polar and neutral lipid classes were separated by HPLC using a two-gradient solvent system. Five polar lipid classes- phosphatidylcholine (PC), phosphatidylethanolamine (PE), cardiolipin (CL), sphingomyelin (SM), and phosphatidylserine (PS)--were identified from P. marinus extracts. Four neutral lipid classes--triacylglycerol (TAG), steryl ester (SE), cholesterol (CHO), and fatty alcohol--were distinguished. TLC/FID analysis of meront lipids showed that the weight percentages of PC, PE, CL, SM, PS/PI, TAG, SE, and CHO were 21, 10.7, 4, 2.3, 4.3, 48.7, 7.8, and 1.2%, respectively. HPLC and HPTLC analyses revealed the presence of two SM and PS isomers in P. marinus extracts. Perkinsus marinus effectively incorporated FL PC acquired from the medium and metabolized it to various components (i.e., free fatty acid, monoacylglycerol, diacylglycerol, TAG, PE, and CL). Uptake and interconversion of FL PC in P. marinus meronts increased with time. After 48 h the total uptake of fluorescence (FL) was 28.9% of the FL PC added to the medium, and 43% of the incorporated FL resided in TAG. PMID- 11202002 TI - Properties of a fluorescent bezafibrate derivative (DNS-X). A new tool to study peroxisome proliferation and fatty acid beta-oxidation. AB - The first peroxisome proliferator-activated receptor (PPAR) was cloned in 1990 by Issemann and Green. Many studies have reported the importance of this receptor in the control of gene expression of enzymes involved in lipid metabolic pathways including mitochondrial and peroxisomal fatty acid beta-oxidation, lipoprotein structure [apolipoprotein (apo) A2, apo CIII], and fatty acid synthase. By using radiolabeled molecules, it was shown that peroxisome proliferators bind and activate PPAR. As an alternative method, we developed a fluorescent dansyl (1 dimethylaminonaphthalene-5-sulfonyl) derivative peroxisome proliferator from bezafibrate (DNS-X), a hypolipidemic agent that exhibits an in vitro peroxisome proliferative activity on rat Fao-hepatic derived cultured cells. However, until now, the effect of this new compound on the liver of animals and subcellular localization was unknown. In addition to in vivo rat studies, we present a more efficient large-scale technique of DNS-X purification. Treating rats (DNS-X in the diet at 0.3% w/w) for 6 d leads to a hepatomegaly and a marked increase in liver peroxisomal palmitoyl-CoA oxidase activity. We also developed a method to localize and quantify DNS-X in tissues or cell compartment organelles. The primarily cytosolic distribution of DNS-X was confirmed by direct visualization using fluorescence microscopy of cultured Fao cells. Finally, transfection assay demonstrated that DNS-X enhanced the PPAR alpha activity as well as other peroxisome proliferators do. PMID- 11202003 TI - Analysis of the addition products of alpha-tocopherol with phosphatidylcholine peroxyl radicals by high-performance liquid chromatography with chemiluminescent detection. AB - A chemiluminescence-based high-performance liquid chromatographic method was developed for the analysis of the addition products of alpha-tocopherol with phosphatidylcholine-peroxyl radicals (TOO-PC). The TOO-PC eluted from a reversed phase column was reacted with a chemiluminescent reagent consisting of a Cypridina luciferin analog and a lipid-soluble iron chelate in acidic methanol at 50 degrees C, and the generated chemiluminescence was monitored. The detection limit for TOO-PC by this method was about 1 pmol. This method was applied to the detection of TOO-PC in the peroxidized membranes prepared from rabbit erythrocyte ghosts. When the erythrocyte ghosts were peroxidized by the addition of a water soluble free radical initiator, a peak corresponding to TOO-PC was detected on the chromatogram with chemiluminescent detection. The amount of TOO-PC in the erythrocyte membranes increased with the depletion of endogenous alpha tocopherol. The results indicate that this method proved useful for the detection of the TOO-PC formed by the peroxyl-radical scavenging reactions of alpha tocopherol in biological systems. PMID- 11202004 TI - Protective effect of phytic acid hydrolysis products on iron-induced lipid peroxidation of liposomal membranes. AB - Beneficial effects of dietary phytic acid (myo-inositol hexaphosphate; IP6) have often been explained by its strong iron ion-chelating ability, which possibly suppresses iron ion-induced oxidative damage in the gastrointestinal tract. Because phytic acid is hydrolyzed during digestion, this work aimed to know whether its hydrolysis products (IP2, IP3, IP4, and IP5) could still prevent iron ion-induced lipid peroxidation. Studies using liposomal membranes demonstrated that hydrolysis products containing three or more phosphate groups are able to inhibit iron ion-induced lipid peroxidation although their effectiveness decreased with dephosphorylation. Similarly, they also prevented iron ion-induced decomposition of phosphatidylcholine hydroperoxide. These results demonstrate that intermediate products of phytic acid hydrolysis still possess iron ion chelating ability, and thus they can probably prevent iron ion-induced lipid peroxidation in biological systems. PMID- 11202005 TI - A place in history: Paul Broca and cerebral localization. PMID- 11202006 TI - Liver bridging techniques in the treatment of acute liver failure. AB - The introduction of orthotopic liver transplantation in the management of acute liver failure has dramatically increased the survival rates of patients at the cost of removing the patient's native liver and life-long dependence on immunosuppression. However, it is well known that in many patients with acute liver failure the diseased liver has the potential to recover. Death in these patients is often due to increased intra-cranial pressure or infection. Liver bridging techniques are assigned to temporarily provide liver function and enable the native liver to recover in patients with acute liver failure. They represent an attractive alternative to conventional liver transplantation in the management of acute liver failure, since after recovery of the native liver the patient is freed from immuno-suppression with all associated side-effects and risks. Auxiliary liver transplantation, artificial liver support devices and hepatocyte transplantation represent different ways of bridging liver function in acute liver failure. The aim of this review is to present the ideas and principles of these three different liver bridging techniques. We will discuss the relative importance and the future potential of theses bridging techniques in the treatment of acute liver failure by comparing the experimental and clinical results. PMID- 11202007 TI - A new clamping technique for biomechanical testing of tendons in small animals. aprobst@uni-muenster.de. AB - When biomechanical properties of tendons are studied, the technique of clamping the tendons in the testing machine presents a methodological challenge, especially when murine tendons are examined. These short tendons tend to rupture at the transition line to the fixation, leading to false interpretations. Therefore a new clamping technique for investigation of healthy murine Achilles tendons (n = 50) was developed, in which the intramuscular tendon fibers were fixed between two paper strips and the calcaneus was wedged into a conical slot in a wooden block and then mounted in the testing machine (n = 20). This technique was compared with the conventional clamping technique that fixes both ends of the tendon by clamps (n = 15) and an earlier described method that used glue or plastic cement for the fixation of the intramuscular tendon fibers and calcaneus in the testing machine (n = 15). When tested by the new clamping technique, 17 tendons ruptured intratendinously at a mean tensile force of 8.4 +/ 1.1 N. Three Achilles tendons (17%) tore at the site of paper fixation and had to be excluded from investigation. Data from 73% of the measurements fixed by gluing had to be excluded because slippage of the proximal tendon fibers and contamination of the tendon with glue occurred. All the conventionally clamped tendons ruptured at the site of fixation at a mean tensile force of 6.1 +/- 2.3 N (p < .05). This was 30% lower than with the new clamping technique. Thus, the newly developed clamping technique enables investigators to obtain more valid biomechanical studies of the murine Achilles tendon. PMID- 11202008 TI - A comparison of collagen and PTFE patch repair in a rabbit model of congenital diaphragmatic hernia. AB - The use of prosthetic material in severe cases of congenital diaphragmatic hernia is complicated by infection, bowel adhesion, and patch dehiscence. We hypothesized that a bioprosthetic collagen patch would reduce these complications and be remodeled into autogenous tissue over a short period of time. Thirty-two New Zealand White rabbits had two 2 x 2-cm left diaphragmatic defects created. One of these defects was repaired with a collagen bioprosthetic patch (n = 20) and the other with a polytetrafluoroethylene (PTFE) patch (n = 20). Members of a control group (n = 12) had their defects closed primarily. The animals were then placed in either a 6- or 12-week survival cohort. At necrosectomy the repairs were assessed histologically, graded for adhesion formation, and tensiometrically tested. The PTFE patch was noted to have a significantly higher average adhesion grade than the collagen patch. The tensile strength of the two repair methods was statistically equivalent at both time intervals. On histologic examination the collagen patches were surrounded by an increased number of macrophages and fibroblasts. The PTFE patch exhibited no neovascularization or fibroblast deposition at the periphery, but had a much greater surrounding inflammatory response. Thus, there was evidence of early remodeling of the collagen with no increase in the amount of adhesions or loss of strength when compared to the PTFE, while the PTFE patches exhibited a more severe grade of adhesions. PMID- 11202009 TI - Experimental aortic stenosis and corresponding left ventricular hypertrophy in sheep. AB - Left ventricular hypertrophy (LVH) is an independent cardiac risk factor. A simple standard experimental model of inducing LVH for further studies using experimental aortic stenosis in sheep was performed. The aim of this study is to describe animal-specific requirements as well as perioperative therapy, postoperative care, and the use of echocardiography for routine follow-up examinations. Supracoronary aortic banding was performed in 55 female sheep at an age of 6 to 8 months. General anesthesia and an antero-lateral thoracotomy were used. The objective was to achieve pressure gradients of 20 to 30 mm Hg. In addition a 4th intercostal space rib window was created to improve echocardiographic vision. The operations were completed successfully in all animals. Intraoperatively, little severe arrhythmia occurred. During the follow up interval of 8 +/- 1.3 months, 8 animals died, due to incomplete perforation of the ascending aorta (3), chronic heart failure (2), pericardial cyst (1), and respiratory failure and infection (2). All remaining animals were amenable for further studies. Severe LVH was diagnosed with routine echocardiography on follow up. Thus, experimental aortic stenosis in sheep is a safe and relatively simple technique to generate stable LVH. Echocardiography is an easy tool for follow-up evaluations. Due to low complication rates, the sheep model is well suited for further research in LVH. PMID- 11202010 TI - An alternative to synthetic aortic grafts using jejunum. AB - Synthetic materials currently used for arterial grafts can provoke serious complications such as infection, rejection, and incomplete reendothelialization. Porcine small intestinal submucosa (SIS) allografts (homografts) may not share these disadvantages yet still may provide an effective graft alternative. This study was designed to provide additional information concerning the performance of this material when used as an allo-patch graft. A porcine model was selected to enable hemodynamic comparisons to the adult human physiology. Slaughterhouse small intestine was used to prepare the SIS graft material. A well-vascularized section ofjejunum was resected, rinsed, and maintained in 0.9% NaCl solution containing 10% gentamicin. The graft was prepared by removing the serosal layer, inverting the material, and discarding the mucosal surface in a similar manner. The remaining submucosa and stratum compactum constituted the graft material and was subdivided into sizes from 1.5 to 3.0 cm2 tacked to foil for manageability, and was returned to the gentamicin solution. The surgery was initiated with a femoral arterial line in the anesthetized swine, followed by isolation and preparation of the infrarenal aorta for grafting. Cross-clamps were applied and a 1.0 x 1.5-cm section of aortic wall was resected. Two sides of allograft were freed from the foil and sewn into the aorta. Then the remaining sides were removed from the foil and final graft placement was completed. The graft was harvested at postoperative day 28 and presented for microscopic examination. Results confirmed that reendothelialization with neovascularization had occurred during this interval. PMID- 11202011 TI - Study of the effect of colonic mass movements on the rectosigmoid junction with evidence of colo-rectosigmoid junction reflex. AB - Mass movements of the left-sided colon bring the colonic material contained in it to the sigmoid colon. The cause why the colonic contents do not pass directly to the rectum but stop short of the rectosigmoid junction (RSJ) was studied. The study comprised 10 healthy volunteers (mean age 39.2 +/- 10.2 years; 8 men, 2 women). A condomended tube was introduced into the descending colon (DC) per anum. The pressure response of the DC, sigmoid colon (SC), and RSJ to condom inflation with carbon dioxide (CO2) in increments of 10 ml was recorded by means of a three-channel microtip catheter. The responses were registered upon inflation of the upper, middle, and lower third of the DC. The test was repeated after individual anesthetization of the descending colon and the RSJ on separate days. Colonic distension with 10 and 20 ml CO2 produced no significant pressure changes in the DC, SC, and RSJ (p > .05); 30 ml distension effected a pressure rise in both the DC (p < .01) and RSJ (p < .05), but no change in the SC pressure (p > .05); and 40, 50, and 60 ml distension produced pressure changes similar to those obtained with 30 ml distension. The RSJ pressure responded to distension of the saline-injected but not of the anesthetized DC. Thus, the RSJ response to colonic distension affirms the hypothesis of the possible involvement of a reflex, which we term colo-RSJ reflex. This reflex seems to regulate the passage of stools from the colon to the rectum. Further studies are required to investigate its role in the diagnosis of defecation disorders. PMID- 11202012 TI - Development of a human to murine orthotopic xenotransplanted lung cancer model. AB - The goal was to develop a clinically relevant animal model that could be used to assess the efficacy of therapeutic interventions in lung cancer. Two cell lines, noncancerous control (BEAS2-B, immortalized human bronchial-epithelial cell line) and cancerous (BZR-T33, H-ras transformed BEAS2-B) were implanted into nude (athymic) mice. Two groups (n = 10 each) received dorsoscapular subcutaneous injection of 10(6) cells from either cell line. BEAS2-B cells were nontumorigenic, whereas mice with BZR-T33 cells had tumors (9,510 +/- 4,307 mm3) confirmed by histology, and a significantly smaller body weight (BZR-T33, 28.5 +/ 0.49 vs. BEAS2-B, 30.7 +/- 0.75 g, p < .05). The next phase evaluated invasion/metastasis. Two groups (n = 10 each) received 10(6) cells from either cell line injected into tail veins. Animals receiving BZR-T33 cells had a smaller body weight, palpable lung masses (67%), obvious tail masses (44%), and average tumor burden (1,120 +/- 115 mm3), and histology revealed invasion of lung tissue and interstitial hemorrhage. In development of the orthotopic xenotransplanted model, mice (2 groups, n = 10 each) received 10(6) cells from either cell line implanted into the lungs through a tracheotomy. Animals with BZR-T33 cells did not survive past 59 days and had a smaller body weight, increased lung weight, lung masses (100%), and metastatic loci (30%). Magnetic resonance imaging (MRI) confirmed the presence of masses in intubated live mice, later confirmed by histology. In summary, the H-ras transfected cell line developed lung masses following tail-vein injection and endotracheal seeding. Evaluation by MRI allows for a comprehensive model with significant potential in the study of lung cancer. PMID- 11202014 TI - Glycoprotein folding in the endoplasmic reticulum. AB - Our understanding of eukaryotic protein folding in the endoplasmic reticulum has increased enormously over the last 5 years. In this review, we summarize some of the major research themes that have captivated researchers in this field during the last years of the 20th century. We follow the path of a typical protein as it emerges from the ribosome and enters the reticular environment. While many of these events are shared between different polypeptide chains, we highlight some of the numerous differences between proteins, between cell types, and between the chaperones utilized by different ER glycoproteins. Finally, we consider the likely advances in this field as the new century unfolds and we address the prospect of a unified understanding of how protein folding, degradation, and translation are coordinated within a cell. PMID- 11202013 TI - Nucleotide pyrophosphatases/phosphodiesterases on the move. AB - Nucleotide pyrophosphatases/phosphodiesterases (NPPs) release nucleoside 5' monophosphates from nucleotides and their derivatives. They exist both as membrane proteins, with an extracellular active site, and as soluble proteins in body fluids. The only well-characterized NPPs are the mammalian ecto-enzymes NPP1 (PC-1), NPP2 (autotaxin) and NPP3 (B10; gp130(RB13-6)). These are modular proteins consisting of a short N-terminal intracellular domain, a single transmembrane domain, two somatomedin-B-like domains, a catalytic domain, and a C terminal nuclease-like domain. The catalytic domain of NPPs is conserved from prokaryotes to mammals and shows remarkable structural and catalytic similarities with the catalytic domain of other phospho-/sulfo-coordinating enzymes such as alkaline phosphatases. Hydrolysis of pyrophosphate/phosphodiester bonds by NPPs occurs via a nucleotidylated threonine. NPPs are also known to auto(de)phosphorylate this active-site threonine, a process accounted for by an intrinsic phosphatase activity, with the phosphorylated enzyme representing the catalytic intermediate of the phosphatase reaction. NPP1-3 have been implicated in various processes, including bone mineralization, signaling by insulin and by nucleotides, and the differentiation and motility of cells. While it has been established that most of these biological effects of NPPs require a functional catalytic site, their physiological substrates remain to be identified. PMID- 11202015 TI - [Practical aspects of drug resistance in schizophrenia]. AB - About 30-60% of patients with schizophrenia show resistance to neuroleptic treatment. In about 5-20% of them the resistance to antipsychotic treatment appears during the first therapy (primary resistance), however in the rest of patients, treatment resistance develops during 5 to 10 years of the illness (secondary resistance). In addition, another group of 5 to 20% of schizophrenics shows intolerance of therapeutic dosages of neuroleptic drugs. Before the diagnose of treatment resistance has been made, there is the need to reconfirm the diagnosis of schizophrenia, exclusion of other psychiatric disorders, assessment of patients' compliance, drug dosing, as well as pharmacokinetic and pharmacodynamic factors which have an impact on the therapeutic effect of antipsychotic treatment. Clozapine seems to be a "gold standard" for treatment of drug-resistant schizophrenic patients, however new atypical antipsychotics should be considered as a new therapeutic strategy, even before clozapine. The use of adjunctive treatment with carbamazepine, lithium, valproic acid, benzodiazepines and others, is a reasonable strategy, however dangerous drug interaction has to be taken into account. PMID- 11202016 TI - [Neuroleptics, atypical antipsychotics and "awakening"]. AB - Clinical response to the treatment of schizophrenic patients with atypical antipsychotics is sometimes labeled as "awakening". However, there is no general agreement what this term specifically means. The wide range of definitions starts from withdrawal of side effects of classical neuroleptics and goes through psychological phenomena to the definition that postulates arresting of the psychotic process. The paper presents a review of different points of view on "awakening" phenomena as well as problems that are connected with it. Some own experiences and attempts at generalization are presented. They deal with new problems and challenges connected with treatment of patients with acute and chronic schizophrenia with atypical antipsychotics. PMID- 11202017 TI - [The role of obstetric complications in the pathogenesis of schizophrenia]. AB - The article is a review of research data on the occurrence of pregnancy and delivery complications in schizophrenic patients and their possible contribution to developing schizophrenia in adolescence or adulthood. Many studies revealed that subjects who have a positive obstetric complications history are at higher risk of developing schizophrenia. Obstetric complications, especially those resulting in asphyxia, are often mentioned as possible environmental factors that can disturb the brain developmental processes, which can be responsible for developing schizophrenia in the future. Obstetric complications can act as an environmental pathogenic factor in some cases of schizophrenia (for example not genetically conditioned ones). They can also constitute an additional factor that, acting together with other (for example genetic factors, results in schizophrenia phenotype). There are still inconsistent data and many methodological problems concerning obstetric complications studies. The problem requires further investigation with improved and unified methodological procedures applied. PMID- 11202018 TI - [The selectivity, polarity and characteristic features of autistic and syntonic schizophrenia]. AB - In previous papers (3, 4, 5) the author presented a hypothesis concerning important features of clinical picture of paranoid schizophrenia, that is selectivity and polarity (bipolarity). Numerous research works aimed at closer recognition of some differences of clinical picture of paranoid schizophrenia have been conducted under the author's direction. The formation of certain psychopathological proportions discerned by the author has been researched with intentionally elaborated scales. The research results have led to distinguishing autistic and syntonic schizophrenia. PMID- 11202019 TI - [Suicide in Poland as reflected by world trends]. AB - Recent epidemiological trends in Polish suicide rates were compared and found to be somewhat consistent with world-wide trends. In addition, the time-series Polish suicide rate was consistent with some predictions made from Durkheim's classic theory of suicide. Finally, hypotheses about the aetiology of suicide were used to derive a linear regression equation to predict the Polish suicide rate reasonably accurately. PMID- 11202020 TI - [Social views of mental diseases--results of research]. AB - Social reactions for mental diseases are very complex, because contacts between healthy people and the ill ones are limited in our society. People are afraid of all symptoms of mental disability and they think that such people should be isolated in closed institutions. The majority of examined people (79%) think that mentally disabled should be cured. People of different age and level of education state such opinions with the same frequency. At the same time, the majority of examined people (88%), admit that the knowledge about mentally disabled in our society is insufficient. This conviction grows simultaneously with the level of education of respondents. The social idea of factors, which start or condition the formation of mental diseases is very schematic. This idea consists of four main elements i.e.: genetic conditions (heredity of disease), bad conditions of life, everyday stress and low psychical immunity. Although the declaration of openness, the majority of respondents represent low tolerance to problems of mentally disabled and their opinions stigmatize ill people. PMID- 11202021 TI - [Proposal for a modified method of semantic differential diagnosis in testing for stereotyping of the mentally ill patient]. AB - In the paper, a proposal of using the semantic differential (by Osgood) for the research on social perception of mentally ill is presented. It allows for investigation of the basic attributes of the stereotype of psychiatric patient: social character, evaluative aspect, simplification, over-generalization of the opinion and its stiffness. The article presents the pilot results coming from the research in a group of students of psychology (first year of studying), who had no lectures in psychiatry by that time (N = 149). The results lead to the conclusion that the picture of mentally ill has social character, that is--some of its attributes are common for a majority of responders (over 77%). They also confirm (with a high certainty--coming to 79%) that most of mentally ill persons (64-80%) are unpredictable, lost, difficult to understand, introvert, unconscious, not self-possessed, excitable, threatening, aggressive and violent. The results show that in the portrait of mentally ill negative attributes are in majority. This portrait--so one-sided and negative--can be one of the basic predictores of social rejection of mentally ill persons. PMID- 11202022 TI - [The situation in integrated and community-oriented psychiatric treatment institutions with new financial realities]. AB - The author describes the structure and functioning of a psychiatric treatment institution which is integrated and community-oriented. He discusses subsequently its readiness to implement changes and goes through adaptation actions (which have taken place at the cost of stuff and quality and extent of service). The situation after four months of financing by health-care funds has been analysed. Finally, the author presents his remarks regarding the on going changes, concerns for the future and suggests new solutions (e.g., capitalized way of financing psychiatric treatment institutions). PMID- 11202023 TI - [Psychosis induction in sisters]. AB - The purpose of this report is to describe induced visual hallucinations among two sisters. The author suggests that the first sister has probably "organic" visual hallucinations but the second sister has "induced" hallucinations. The paper describes a family of three old maids, living commonly for several years. PMID- 11202024 TI - [Hyperactivity and behavioral disorders in Sanfilippo A (mucopolysaccharidosis type IIIA)--case report and review of the literature]. AB - Sanfilippo syndrome is one of mucopolysaccharidoses. The main symptom of this syndrome is regression of psychomotor development and neurological signs which occur between 2 and 6 years old. Unlike other mucopolysaccharidoses body dysmorfic features are relatively rare. Course of disease is progressive, most of the patients die before 20. The diagnosis is often difficult. In our opinion in each case presenting psychomotor regression of unknown origin metabolic disease should be excluded (e.g. urine analysis for mucopolysaccharides should be indicated). A 6 year old boy has been under psychiatric and psychological control since he was 3 due to psychomotor retardation, hyperactivity, autistic features, and behavioural disorder. In paediatric examination thickened facial features, coarse hair, knock-knees, short neck were noted. Genetic consultation set up the diagnosis of mucopolysaccharidosis type IIIA (Sanfilippo A disease). PMID- 11202025 TI - Renovation of contaminated building materials at a facility serving pediatric cancer outpatients. PMID- 11202026 TI - Cercopithecine herpesvirus 1 (B virus) infection resulting from ocular exposure. PMID- 11202027 TI - An occupation-industry matrix analysis of mesothelioma cases in Australia 1980 1985. AB - Australia has one of the highest national incidences of mesothelioma in the world and the rate is still rising. An industry-occupation matrix analysis was conducted for the 858 mesothelioma cases that were reported to the Australian Mesothelioma Surveillance Program between 1980 and 1985. Definite, probable, or possible occupational exposure had occurred in 57 percent (492/858) of the subjects. The primary asbestos production or manufacturing industry constituted the largest number of cases (137/492, 27.8%), followed by shipbuilding, repair and demolition (114/492, 23.2%), the building industry (69/492, 14.1%), and the railway locomotive construction and maintenance industry (47/492, 9.6%). Laborers constituted 14.8 percent (n = 73) of the occupations with a history of exposure to asbestos, followed by carpenters (13.0%, n = 64), boilermakers (10.6%, n = 52), and fitters/turners (8.1%, n = 40). The distribution of occupations in specific industries is presented in this article. PMID- 11202028 TI - Experimental evaluation of an environmental CAT scanning system for mapping chemicals in air in real-time. AB - An innovative method is being developed which creates real-time, two-dimensional maps of chemical concentrations in air for environmental and occupational applications. This method, we call environmental CAT scanning, combines the real time measuring technique of open-path Fourier transform infrared spectroscopy with the mapping capabilities of computed tomography to produce accurate spatial and temporal information about contaminant concentrations and dispersion patterns. With this system, a network of open-path measurements is obtained over an area; measurements are then processed using a tomographic algorithm to reconstruct the concentrations. This article describes a thorough experimental evaluation of an environmental CAT scanning system using a field-ready prototype system deployed in a room-size exposure chamber; point sample measurements were taken simultaneously in the chamber along with the CAT measurements. Twenty-eight experiments were performed using single or multiple plumes of a tracer gas in the chamber. Tomographic maps were compared with the point sample reference maps to evaluate the CAT scanning system for accuracy of concentration measurement and plume location. Quantitative agreement was very good; concentrations reconstructed with the tomographic maps agreed to within 17 percent of the point sample maps, and plume locations were reconstructed to within six inches of the plumes in the point sample maps. This technique shows real promise as a rapid and accurate method for mapping chemicals over large areas. PMID- 11202029 TI - The reliability of multiple regression and an alternative method for extracting task-specific exposure estimates from time-weighted average data. AB - The reliability of multiple regression analysis as a method for determining task specific exposures from multi-task time-weighted average data was evaluated in comparison with the alternative P-screen method. The performances of the two methods were tested using simulated sample data that were calculated as averages over six tasks, where task-specific concentrations drawn randomly from lognormal distributions were weighted by randomly generated task time-weights. Data sets consisted of 20 or 100 simulated samples. The simulated data sets conformed to requirements inherent in the P-screen method that at least one task be absent from each sample and each task be absent from at least one sample. In thousands of Monte Carlo trials under various conditions, the two methods were found to perform equally well when dichotomous task measures (occurrence/ nonoccurrence) were used. Combining the two methods did not improve reliability appreciably, suggesting that the methods are effectively equivalent when dichotomous task measures are used. When task durations were used as the regressors or time weights, multiple regression was found to be more reliable than P-screen. It is well recognized that incidental or fundamental collinearities between regressors may undermine multiple regression analyses. The P-screen-related restrictions on the task structure of data sets reduces the potential for problems arising from such collinearities. However, the use of multivariate analysis of multiple-task samples will always be an imperfect substitute for single-task sampling. PMID- 11202030 TI - Exposure to chemical agents in Swedish aluminum foundries and aluminum remelting plants--a comprehensive survey. AB - Secondary aluminum melting is mainly performed in sand, die, and static die casting foundries and remelting plants. In seven Swedish foundries and two remelting plants, the exposure and area concentrations of total dust, metals, organic gases, and vapors were determined mainly as daily, time-weighted averages (TWAs). For most combinations of jobs and agents, the exposure levels were well below the current threshold limits suggested by the American Conference of Governmental Industrial Hygienists (ACGIH). However, high exposure levels of mineral oil mist (geometric mean [GM] = 0.6 mg/m3) were observed in the die casting process, with a maximum of 4 mg/m3. The findings were similar for total dust (GM = 5.1 mg/m3) and crystalline quartz (GM = 0.05 mg/m3) during molding operations in the sand foundries, maximum air concentrations being 31 mg/m3 and 0.22 mg/m3, respectively. Other agents which occasionally reached high exposure levels included furfuryl alcohol (up to 23 mg/m3 during furan binder use in sand foundries), aniline (up to 2.6 mg/m3 during thermal degradation of cold-box binders), and dimethylethylamine (up to 9 mg/m3) in the cold-box process used in static die-casting and sand foundries. The average aluminum exposure levels (GM = 0.043 mg/m3) were low in all foundries, individual values not exceeding 0.94 mg/m3. The exposures to metals were below 10 percent of their threshold limits. Similarly low levels were detected of polyaromatic hydrocarbons, phenol, formaldehyde, methylenebisphenyl diisocyanate, and phenylisocyanate. In the aluminum remelting plants, a few high exposure levels of total dust (GM = 1.4 mg/m3) up to 8 mg/m3 were detected in furnace workers. Aluminum and other metals were well below 10 percent of their threshold limits, with the exception of a few high concentrations of manganese, up to 0.14 mg/m3. The between-worker variability (GSDB) in the foundries for total dust, aluminum, and oil mist were on the order of 3-4. The heterogenicity of secondary aluminum melting requires assessment of a wide variety of chemical agents. For certain exposures, technical and medical monitoring programs are still needed. PMID- 11202031 TI - Comparison of a direct-reading device to gravimetric methods for evaluating organic dust aerosols in an enclosed swine production environment. AB - The production of livestock in enclosed facilities has become an accepted practice, driven by the need for increased efficiency. Exposure to organic dusts, containing various bioactive components, has been identified an important risk factor for the high rate of lung disease found among workers in these environments. Assessment of organic dust exposure requires technical skills and instrumentation not readily available to most agricultural enterprises. Development of a simple, cost-effective method for measuring organic dust levels would be useful in evaluating and controlling exposures in these environments. The objective of this study was to evaluate the usefulness of the direct reading MIE PDM-3 Miniram for estimating organic dust concentrations in enclosed swine production facilities. Responses from the MIE PDM-3 Miniram were compared to gravimetric methods for total and inhalable dust. Total dust determinations were conducted in accordance with the National Institute for Occupational Safety and Health (NIOSH) method 0500. Inhalable particulate mass (IPM) sampling was conducted using SKC brand IOM (Institute of Occupational Medicine) sampling cassettes, which meet the American Conference of Governmental Industrial Hygienists ACGIH criteria for inhalable dust sampling. This study design also allowed for the comparison of traditional total dust method to the IPM method, in collecting organic dusts in an agricultural setting. Fifteen sets of side-by-side samples (Miniram, total dust, and IPM) were collected over a period of six months in a swine confinement building. There were statistically significant differences in the results provided by the three sampling methods. Measurements for inhalable dust exceeded those for total dust in eleven of fifteen samples. The Miniram time weighted average (TWA) response to the organic dust was always the lower of the three methods. A high degree of correlation was found among all three methods. The Miniram performed well under field conditions of varying temperature and humidity. The Miniram has the potential to predict the inhalable and total dust concentrations, assuming a correction factor for the organic dust being measured is applied. PMID- 11202032 TI - Comparison of occupational exposure using three different methods: hygiene panel, job exposure matrix (JEM), and self reports. AB - This study was undertaken to compare the agreement of occupational exposure assessment by a panel of occupational hygienists with a job exposure matrix and self-reported exposures in a community-based case-control study. We also investigated the intra-rater reliability and degree of attenuation of the hypothetical odds ratio of the panel in retrospective chemical exposure assessment. A panel of three occupational hygienists was recruited to assess exposure to chemicals for 5,620 jobs. The agreement between the panel, a job exposure matrix (FINJEM), and the self-reported exposures was then assessed. A further 172 jobs were resubmitted to the panel to assess intra-rater reliability. The kappa for intra-rater reliability ranged from 0.60-0.71. The agreement between the panel and FINJEM ranged from 0.07 to 0.46 (for similar exposures), and agreement between the panel and among the self-reports ranged from 0.00 to 0.48. Agreement between hygienists when rating exposure to the same chemical ranged from 0.48 to 0.57. Based on these findings, the degree of exposure misclassification by the panel where the true odds ratio was 2 would result in the observed odds ratio ranging between 1.70 and 1.88. The results indicated good intra-rater reliability for the hygiene panel. However, the agreement among the panel, FINJEM, and self-reported exposures was found to be only poor to fair. The attenuation of the odds ratios due to exposure misclassification by the panel was variable and dependent upon the exposure. PMID- 11202033 TI - Social policy implications of research in developmental psychopathology. PMID- 11202034 TI - Stigma and mental disorder: conceptions of illness, public attitudes, personal disclosure, and social policy. AB - The end of the last millennium witnessed an unprecedented degree of public awareness regarding mental disorder as well as motivation for policy change. Like Sartorius, we contend that the continued stigmatization of mental illness may well be the central issue facing the field, as nearly all attendant issues (e.g., standards of care, funding for basic and applied research efforts) emanate from professional, societal, and personal attitudes towards persons with aberrant behavior. We discuss empirical and narrative evidence for stigmatization as well as historical trends regarding conceptualizations of mental illness, including the field's increasing focus on genetic and neurobiological causes and determinants of mental disorder. We next define stigma explicitly, noting both the multiple levels (community, societal, familial, individual) through which stigma operates to dehumanize and delegitimize individuals with mental disorders and the impact of stigma across development. Key developmental psychopathology principles are salient in this regard. We express concern over the recent oversimplification of mental illness as "brain disorder," supporting instead transactional models which account for the dynamic interplay of genes, neurobiology, environment, and self across development and which are consistent with both compassion and societal responsibility. Finally, we consider educational and policy-related initiatives regarding the destigmatization of mental disorder. We conclude that attitudes and policy regarding mental disorder reflect, in microcosmic form, two crucial issues for the next century and millennium: (a) tolerance for diversity (vs. pressure for conformity) and (b) intentional direction of our species' evolution, given fast-breaking genetic advances. PMID- 11202035 TI - Developmental psychopathology and public health: past, present, and future. AB - Children's healthy mental development has never been the focus of long-term, committed public health policy in the way that early physical health and development have been. We discuss four types of societal response to illness cure, care, control, and prevention--and trace the history of public health in terms of its special responsibility to control and prevent disease. We identify four periods in the history of public health: the Sanitarian era (up to 1850), the Bacterial era (1850-1950), the Behavioral era (1950-present), and the Communitarian era (the next century). Looking at this history from the viewpoint of the developmental psychopathology of the first 2 decades of life, we trace progress in public health responses to children with mental illness, from a philosophy of control by isolation toward one of preventive intervention. We examine primary, or universal, prevention strategies that have been tried, and we suggest some that might be worth reconsidering. PMID- 11202036 TI - Welfare reform, family support, and child development: perspectives from policy analysis and developmental psychopathology. AB - This article explores the implications of recent welfare-related policy change for the well-being of children in low-income families, and for research investigating child development processes and outcomes. It provides an overview of current welfare-related policies and explores the implications for developmental researchers. The article also synthesizes early findings from research, highlighting both overall impacts and the more nuanced evidence that while families are transitioning off welfare, only a small number are transitioning out of poverty, and a subgroup of families at risk are not faring well. It then examines, from a theoretical and methodological framework, what developmental psychopathology might bring to the study of welfare-related impacts on children in the context of this complex and changing policy landscape, and what welfare researchers might bring to the field of developmental psychopathology. The article concludes with broad recommendations for both research and policy. PMID- 11202037 TI - Changes in womens' roles: impact on and social policy implications for the mental health of women and children. AB - In recent years. womens' roles have changed dramatically, prompting researchers to examine the impact of these changes on the development of women and children. In this article, we examine three major changes that women have experienced over the past several decades: increased participation in the paid labor force, changes in domestic labor and child-care patterns, and increased numbers of female-headed single-parent families. For each, we first describe the nature of the changes that have occurred over the last 50 years. We then review research concerning the effects of these changes on the development of women and children. Finally, we discuss the implications for social policy that stem from this research. It is broadly concluded that research informed by a developmental contextual perspective may contribute importantly to the development of social policies focused on promoting the well-being of women and children. PMID- 11202038 TI - Striving to do well what comes naturally: social support, developmental psychopathology, and social policy. AB - Social support can have significant stress-preventive and stress-buffering benefits for troubled individuals in everyday circumstances. Consequently, it is not surprising that many therapeutic and preventive programs enlist social support to address problems of child and family psychopathology, especially in the context of "two-generation interventions" that seek to improve child well being by strengthening parental functioning and parent-child relationships. Home visitation programs are the best known of these two-generation strategies and have become the focus of state-level and national efforts to support families and prevent harm to children. The conclusions of basic research studies on social support converge significantly with the findings of evaluation studies of the impact of home visitation programs to yield important new insights into the conditions in which formal social support is likely to be beneficial. or ineffective, in improving child and family well-being. Both basic and applied research literatures emphasize the importance of linking formal social support to informal social networks in extended families, neighborhoods, and communities, and attending to the complex reactions of the recipients of support and the needs of support providers. These studies are reviewed and evaluated to highlight the connections between social support, developmental psychopathology. and social policy. PMID- 11202039 TI - International adoption of institutionally reared children: research and policy. AB - This article summarizes the research on the developmental outcomes of postinstitutionalized children and discusses the implications for social policy. Postinstitutionalized children often reach their adoptive families with varying degrees of physical growth retardation, cognitive delays, and socioemotional problems. Many children demonstrate remarkable recovery following adoption. Unfortunately, some of the children continue to display significant problems that require professional intervention. It appears that the children's recovery may be influenced by their early experiences with their birth family and in institutional care, and there is suggestive evidence that postadoption experiences also play a role. These findings indicate that preadoption and postadoption services may support the outcome of postinstitutionalized children. PMID- 11202040 TI - The role of early experience in shaping behavioral and brain development and its implications for social policy. AB - This article provides a targeted review of the scientific literature on the effects of experience on early brain and behavioral development and later outcome as it pertains to risk for some forms of child psychopathology. It is argued that ample evidence exists indicating that the prenatal and early postnatal years likely represent a sensitive period with respect to the effects of stress on the developing nervous system and behavioral outcome, and with respect to the long term beneficial effects of early interventions on brain and behavioral development for some genetically based disorders, such as phenylketonuria and autism. Moreover, evidence suggests that parental mental health during the first years of life has a significant influence on early brain activity and behavior, and long-term behavioral outcome. It is concluded that, although prevention and early intervention efforts should not exclusively focus on the earliest years of development, such efforts should begin during this period. By directing such efforts toward promoting optimal prenatal and infant-toddler development, the long-term negative consequences of factors that have their greatest influences during early development and which set the stage for future development can be minimized or avoided entirely. Several recommendations for public policy and future research pertaining to the effects of early experience on child outcome are offered. PMID- 11202041 TI - Conceptualizing mental disorders in children: where have we been and where are we going? AB - Conceptions of mental illness in children are bound by cultural and social conventions of what constitutes healthy and unhealthy development. To understand current conceptualizations of disorders in children, we review the history of these conceptualizations from three intertwined perspectives: a sociopolitical history of American children and families, the history of the mental health fields and scientific disciplines involved in diagnosing children, and the evolution of children's role in the Diagnostic and Statistical Manual of Mental Disorders. We review where the field has been in its conception of childhood mental illness throughout the past century, where we believe it is now, and raise questions about the direction in which child diagnosis may be headed as we enter the new millennium. We conclude with social policy recommendations based on theory and research regarding mental disorders in children. PMID- 11202042 TI - Young children who commit crime: epidemiology, developmental origins, risk factors, early interventions, and policy implications. AB - An early onset of delinquency prior to age 13 years increases the risk of later serious, violent, and chronic offending by a factor of 2-3. Also child delinquents, compared to juveniles who start offending at a later age, tend to have longer delinquent careers. This article summarizes the report of the Office of Juvenile Justice and Delinquency Prevention's Study Group on Very Young Offenders, chaired by Rolf Loeber and David P. Farrington. The Study Group, consisting of 16 scholars and 23 coauthors, worked for 2 years on preparing a report, undertaking extensive secondary data analyses, and writing chapters in different speciality areas. The report consists of a state of the art review of the developmental background of child delinquents. The report also summarizes risk and protective factors in the individual, family, peer group, school, and neighborhood that affect that development. Lastly, the report renews relevant preventive and remedial interventions in the juvenile justice system, families, peer groups, schools. and neighborhoods, and makes a case for improvement in the integration of services for child delinquents. Policy recommendations are presented to improve methods of dealing with child delinquents by juvenile justice, child welfare, and mental health agencies. PMID- 11202043 TI - Problem behavior: the double symptom of adolescence. AB - In this article we address several issues regarding problem or antisocial behavior in adolescents. First, we discuss conceptualizations of adolescent problem behavior to answer the question 'What do we think we know so far?" Then, we briefly characterize current interventions designed to reduce these behaviors, and their relative success in doing so. Next, we examine earlier attempts to prevent and ameliorate problem behavior (including juvenile delinquency), situating them in the historical context of America from the turn of the century to World War II. Here, we attempt to answer the questions "How did we get to where we are?" and "How can we learn from the past?" Following this, we try to answer the question "Where do we go from here?" and articulate some research and policy implications relevant to developmental psychopathology that arise from these considerations. We argue that problem behavior is viewed most productively in its double aspect, which John Hughlings Jackson called a "double symptom," with the positive aspect of the symptom reflecting adolescents' attempts to satisfy their developmental needs. PMID- 11202044 TI - Drug abuse and developmental psychopathology. AB - Drug abuse research and theory has become much more sophisticated over the last 2 decades, and some of the advancements parallel concepts that are part of the developmental psychopathology approach. The application of the developmental psychopathology perspective to recent drug abuse research findings can provide a greater understanding of that information and point to important areas of future research. Among the drug abuse research areas discussed here and viewed from this perspective are antecedent and co-occurring psychopathological conditions and other problem behaviors; the diversity of the nature of, paths to, and processes and outcomes related to drug abuse; the role of intermediary influences; the interaction of individual and environmental predisposing and protective factors; the role of families and other social institutions in intervention; and developmental stage characteristics. Directions for future research are also discussed. PMID- 11202045 TI - Social policy and prevention in mental health. AB - This article presents policy recommendations relating to two aspects of primary prevention in mental health: (a) preventing adverse negative outcomes and (b) building health and wellness from the start and maintaining it thereafter. Recommendations for reducing diverse negative outcomes and end states reflect interconnections and bidirectional influences among physical, social interpersonal, cognitive-academic, and "mental health" outcomes. PMID- 11202046 TI - A developmental psychopathology perspective on child and adolescent treatment policy. AB - This article considers the implications of theory and research in developmental psychopathology for existing and emerging social policy concerning treatment of child and adolescent psychopathology. Based on the concept that all psychopathology is a process, four core principles of a developmental psychopathology perspective are discussed. In turn, each is applied to an evaluation of policy issues with implications for intervention, including mental health parity, treatment guidelines, mental health reimbursement, and level of intervention. It is concluded that social policy on treatment must be based on an empirically supported theory of developmental psychopathology and on evidence based interventions that link treatments to pathogenic processes. PMID- 11202048 TI - Porphyrins, porphyrin metabolism and porphyrias. I. Update. AB - The biosynthesis of porphyrins is one of the most conserved parthways known, about the same sequence of reactions taking place in all species. By associating different metals, porphyrins give rise to the "pigments of life": chlorophyll, haem and cobalamin. The unique tetrapyrrolic structure enables it to function in an array of reactions as a single electron carrier and as a catalyst for redox reactions. In this capacity, it constitutes the prosthetic group of enzymes participating in cellular respiration, in conversion reactions involving steroids and lipophilic xenobiotics, in protective mechanisms directed against oxidative stress and in pathways providing central messenger molecules. The formation of haem is accomplished by a sequence of eight dedicated enzymes encoded by different genes, some being active in ubiquitous as well as in erythroid isoforms. Large differences between the participating enzymes with regard to catalytic power, with low capacity steps positioned early in the catalytic chain, constitute a bar against substrate overloading of enzymes processing porphyrins, thus preventing accumulation in the body of these phototoxic compounds under physiological conditions. Most of the haem in the body is produced by the liver and bone marrow, but the mechanisms applied for the control of the synthesis differ between the two organs. The extremely potent hemeprotein enzymes formed in the liver are rapidly turned over in response to current metabolic needs. They have half-lives in the order of minutes or hours and are restored by fast-acting mechanisms for the de novo synthesis, when needed. Uninterrupted and instant availability of the compound is secured by acute deinhibition of the initial enzyme of the synthetic chain, ubiquitous 5-aminolevulinate synthase (ALAS-1), in response to drain of the free cellular haem pool caused by prevailing demands for hemeproteins or by increased catabolism of the compound. In contrast, in the erythroid progenitor cell the haem synthetic machinery is designed for uninterrupted production of huge amounts of haem for combination with globin chains to form hemoglobin at a steady rate. In the erythron the synthesis of the enzymes participating in the formation of haem is under control of erythropoietin, formed under hypoxic conditions. In the absence of iron, to be incorporated in the porphyrin formed in the last step of the synthesis, the mRNA of erythroid 5-aminolevulinate synthase (ALAS-2) is blocked by attachment of an iron-responsive element (IRE) binding cytosolic protein, and transcription of this key enzyme is inhibited. In humans, the genes for each of the haem synthetic enzymes may become the target of mutations that give rise to impaired cellular enzyme activity. Seven of the enzyme deficiencies are associated with accumulation of toxic intermediaries and with disease entities termed porphyrias. The acute porphyrias are characterized by attacks of neuropsychiatric symptoms, which may be due to a toxic surplus of the porphyrin presursor 5-aminolevulinic acid, or a consequence of a deficit of vital hemeproteins resulting from impaired synthesis of haem. In the cutaneous porphyrias, impairment of enzymatic steps where porphyrins are processed gives rise to solar hypersensitivity due to accumulation of phototoxic porphyrins in the skin. Early diagnosis, information to the patient regarding the nature of the illness and counselling aimed at avoidance of triggering factors are cornerstones in the handling of the porphyric diseases. Gene analysis is of incomparable diagnostic reliability in carrier detection, but biochemical methods must be applied in the important task of monitoring porphyric disease activity. In most forms of porphyria the gene carriers run the risk of development of associated diseases in liver or kidneys, a circumstance that prompts application of well-structured surveillance programs. PMID- 11202049 TI - Porphyrins, porphyrin metabolism and porphyrias. II. Diagnosis and monitoring in the acute porphyrias. AB - The acute porphyrias constitute a group of metabolic disorders engaging enzymes in the haem synthetic chain and generally following dominant inheritance patterns. Some gene carriers are vulnerable to a range of exogenous and endogenous factors, which may trigger neuropsychiatric symptoms. Early diagnosis is of prime importance since it makes way for counselling with the aim to block the development of acute, as well as late, disease. The medical and psycho-social consequences of a porphyria diagnosis are considerable and the freedom for maldiagnosis correspondingly small. The strain imposed upon the diagnostic process makes management in specialized laboratories necessary. Inadvertent handling of the diagnostic procedures in laboratories lacking in knowledge, experience and technical competence is repeatedly the reason for harmful underdiagnosis and overdiagnosis. Gene diagnosis of the carrier condition, principally within reach in all types of acute porphyria, is of incomparable versatility and accuracy. However, despite recent great achievements in the molecular biology of porphyric disease, genomic procedures cannot replace biochemical methods in monitoring the activity and progress of the disease, or the effects of therapy. The classical methods are also useful when it comes to screening for the associated disease states. In these tasks, professional handling of the methods and skillful interpretation of the results are of paramount importance. Knowledge of the limitations and pitfalls of the procedures is a guard against maldiagnosis, which may be fatal. In the article the main diagnostic challenges are discussed; the strategy for early detection of the gene carrier state, the recognition and surveillance of the acute porphyric crisis, the evaluation of subacute/subchronic symptoms, the differential diagnoses of the cutaneous porphyrias and the monitoring of late complications. PMID- 11202050 TI - Porphyrins, porphyrin metabolism, porphyrias. III. Diagnosis, care and monitoring in porphyria cutanea tarda--suggestions for a handling programme. AB - Deficiency of the fifth enzyme in haem synthesis, uroporphyrinogen decarboxylase (UPGD), may give rise to accumulation and excretion of poly-carboxylated porphyrins, as well as to clinical manifestations in the form of a phototoxic skin reaction and liver engagement leading to cirrhosis and hepatocellular cancer. The cutaneous reaction, presenting as skin fragility and blisters on areas exposed to sun--porphyria cutanea tarda (PCT)--develops only in individuals with a remaining hepatic UPGD activity less than 20% of normal. Experimental results and clinical observation give evidence that PCT is a multifactorial disease. In some individuals a 50%, decrease in UPGD activity is a consequence of inheritance of an allele with a mutation in the gene programming for the enzyme, but in these gene carriers, as well as in the other patients with overt PCT, the activity of the hepatic enzyme is reduced below the critical level by the action of specific inhibitors. In the generation of the enzyme inhibitors, iron plays a central role by promoting the formation of reactive oxygen species, a process where a specific class of cytochrome enzymes; cytochrome P450 1A (CYP4501A), participates. The varying individual susceptibility to development of the disease can be discussed in terms of differences in a spectrum of factors that affect the availability of the free form of this element in the liver, or its pathogenic action. In the article the roles of chronic viral infection, alcohol abuse and exposition to polyhalogenated cyclic hydrocarbons are considered in the light of effects on the availability of iron in the liver. Some genetic prerequisites for susceptibility to PCT-inducing agents are included in a tentative model for the disease, i.e. mutations in the UPGD gene and in the HFE gene affected in haemochromatosis, as well as genetically steered inducibilities of the genes programming for CYP4501A and the rate-limiting enzyme in haem synthesis, 5 aminolevulinate synthase. With the pathogenic model as a basis the different therapeutic strategies that can be applied are discussed, and suggestions for a handling programme for the patient presenting with PCT put forward. PMID- 11202047 TI - The construct of resilience: implications for interventions and social policies. AB - The focus of this article is on the interface between research on resilience-a construct representing positive adaptation despite adversity--and the applications of this work to the development of interventions and social policies. Salient defining features of research on resilience are delineated, as are various advantages, limitations, and precautions linked with the application of the resilience framework to developing interventions. For future applied efforts within this tradition, a series of guiding principles are presented along with exemplars of existing programs based on the resilience paradigm. The article concludes with discussions of directions for future work in this area, with emphases on an enhanced interface between science and practice, and a broadened scope of resilience-based interventions in terms of the types of populations, and the types of adjustment domains, that are encompassed. PMID- 11202051 TI - Porphyrins, porphyrin metabolism and porphyrias. IV. Pathophysiology of erythyropoietic protoporphyria--diagnosis, care and monitoring of the patient. AB - An extremely painful cutaneous condition with no or only slight visible skin changes, presenting in a child or an adult as an acute reaction to sun light, is probably a manifestation of the porphyrin metabolic disorder erythropoietic protoporphyria (EPP). The disease is the result of a genetically determined condition where a mutation in the gene for the final enzyme in the haem synthetic chain, ferrochelatase, results in impaired activity of the enzyme. In some predisposed individuals, the condition is accompanied by heavy accumulation of the substrate for the deficient enzyme, i.e. of protoporphyrin. Distributing to the skin, and there absorbing light of certain wavelengths, the metabolite generates free radicals that give rise to photodynamic cell injury. The primary event takes place in the endothelial cells of the superficial skin capillaries, but complement activation and mast cell degranulation in the surrounding tissue follow in the process. Even if the disease is primarily dermatological the hepatic and psychosocial complications are features requiring close attention by the physician. In order to provide a basis for suggestions regarding lege artis protocols for the diagnosis, treatment and monitoring of the patient with EPP, the pathophysiology of the cutaneous and hepatic manifestations are discussed in some detail in the article. PMID- 11202052 TI - Diagnosis of variegate porphyria--hard to get? AB - Variegate porphyria (VP) is an inherited metabolic disease that results from the partial deficiency of protoporphyrinogen oxidase. In this communication we have used DNA technology in the diagnosis of VP and compared the results with the biochemical and clinical data. To date, we have diagnosed 107 VP patients using either biochemical or DNA techniques or both. In addition, in 106 family members the diagnosis of VP could be excluded. The sensitivity and specificity of the biochemical screening for VP were studied among 38 family members. These individuals were either asymptomatic (n = 19) or had experienced occasional skin symptoms (n = 13), acute attacks (n = 5) or both (n = 1). The sensitivity of urinary and fecal coproporphyrin analysis was 48% and 52%, respectively. The sensitivity of urinary uroporphyrin analysis was 71% and for fecal protoporphyrin 77%. Plasma fluorescence was sensitive in symptomatic patients even in remission, but resulted in false negatives in four asymptomatic patients with normal excretion of porphyrins in the urine. In our series of mutation screening, many new asymptomatic patients were identified, and this demonstrated that DNA analysis is the only reliable way to screen (a)symptomatic patients facilitating correct treatment and proper genetic counselling of family members at risk. Biochemical analyses (e.g. plasma fluorescence, fecal protoporphyrins, urinary copro- and uroporphyrins, porphobilinogen and delta-aminolevulinic acid) are essential when the diagnosis of VP is confirmed at the symptomatic phase. PMID- 11202053 TI - Uroporphyrinogen decarboxylase gene mutations in Danish patients with porphyria cutanea tarda. AB - Decreased uroporphyrinogen decarboxylase (UROD) activity is a characteristic feature of the most common of the porphyrias, porphyria cutanea tarda (PCT). A subgroup of the clinically overt PCT cases is associated with mutations in the gene encoding UROD and inherited as an autosomal-dominant trait. In this study, DNAs from 53 Danish PCT patients were subjected to genetic analysis for UROD mutations using denaturing gradient gel electrophoresis. Eleven genetic variations, seven of which are possible disease causing, were identified. All but one of these mutations were previously unknown, lending further support to the assumption that PCT is a heteroallelic disease. Only 11% of the examined patients were previously recognized as familial PCT cases. However, possible disease related UROD mutations were identified in 24% of the examined patients, indicating that genetic analysis of PCT patients may improve differentiation between familial and sporadic PCT cases. PMID- 11202054 TI - DGGE analysis of the coproporphyrinogen oxidase gene: two new mutations in DNA from Danish patients with hereditary coproporphyria. AB - The knowledge of at least 21 different mutations and several polymorphisms in the coproporphyrinogen oxidase (CPO) gene demonstrates that the molecular basis of hereditary coproporphyria is heterogeneous. We developed a DGGE-based assay for the analysis of exons 2 to 7, including 14-96 nucleotides of the flanking intronic sequences of the CPO gene. To render it suitable for the clinical diagnostic laboratory, we designed the assay to allow use of identical PCR conditions and the same DGGE gel for analyses of all the regions. Using this assay, and subsequent sequencing of gene regions containing interallelic variations, two novel mutations in the CPO gene were identified: a missense mutation (607G-->A), leading to the substitution of an alanine with a threonine, and a nonsense mutation (1281G-->A), giving rise to a stop codon 28 codons upstream to the wild-type stop codon. PMID- 11202055 TI - Determination of porphobilinogen deaminase activity in human erythrocytes: pertinent factors in obtaining optimal conditions for measurements. AB - Determination of porphobilinogen deaminase (PBGD; EC 4.3.1.8) activity in erythrocytes can contribute to the identification of patients suspected of acute intermittent porphyria. PBGD catalyses the polymerization of four molecules of porphobilinogen (PBG) to the highly unstable 1-hydroxymethylbilane. The 1 hydroxymethylbilane is transformed into uroporphyrinogen III by uroporphyrinogen III synthase. When this enzyme is inactivated, 1-hydroxymethylbilane cyclizes non enzymatically to uroporphyrinogen I, which can be oxidized to uroporphyrin I. PBGD activity can be measured by quantitation of uroporphyrin I formed from PBG under conditions where this is the only end product. The purpose of the present study was to define the optimal conditions for quantitating PBGD activity in human erythrocytes. The preanalytical factors examined were: anticoagulants and methods for disruption of the erythrocytes. The analytical factors examined were: duration of preincubation, reaction time, reaction temperature, pH, ionic strength and conditions for the oxidation of uroporphyrinogen I to uroporphyrin I. Based on the results, we propose an optimized method for determination of PBGD activity in erythrocytes. PMID- 11202056 TI - Activity and immunohistochemical localization of porphobilinogen deaminase in rat tissues. AB - Porphobilinogen deaminase (PBGD) is an enzyme involved in the synthesis of heme. Acute intermittent porphyria (AIP) is an inherited disease resulting from a reduced activity of PBGD. The symptoms seem to be due to a neurological dysfunction. Attacks of AIP are often provoked by conditions where the PBGD activity becomes insufficient as a result of an increased synthesis of heme in the liver. How this affects the nervous tissue is still unknown. It may well be that a reduced activity of PBGD in other tissues than the liver is of importance too. The aim of the present study was to examine the activity and the immunohistochemical localization of PBGD in the following tissues of wistar female rats: brain, heart, submandibular gland, liver, kidney, pancreas, ovary, stomach, duodenum, jejunum, ileum, colon and musculature. The PBGD activity varied considerably among the tissues. It was highest in the liver, 14 pkat/g, and lowest in the jejunum, 0.7 pkat/g. The immunohistochemical localization of PBGD was studied by antibodies raised against a 40 amino acid synthetic peptide that corresponds to a segment in the C-terminal part of PBGD. The study demonstrated that the PBGD immunoreactivity was not evenly distributed among the various cell types in a given tissue. Immunohistochemical reactions were pronounced in Kupffer cells in the liver, in smooth muscle cells of arteries and arterioles, in distal and collecting tubules in the kidney, in nerve axons in the brain and in ganglionic cells in the intestine. Especially, the immunohistochemical reaction in nerve cells is notable considering the nervous dysfunction in AIP. PMID- 11202057 TI - The W198X and R173W mutations in the porphobilinogen deaminase gene in acute intermittent porphyria have higher clinical penetrance than R167W. A population based study. AB - In northern Sweden, 468 patients with DNA-verified acute intermittent porphyria (AIP) were registered. A higher prevalence of manifest AIP was found in patients with mutations W198X and R173W when separately compared with mutation R167W, indicating higher clinical penetrance. Signs of increased seriousness of the disease were also found in patients with the W198X and R173W mutations in relation to the number and duration of attacks, impaired renal function and chronic disability. One explanation could be lower PBGD enzyme activity resulting from the W198X and R173W mutations than from the R167W mutation, though other factors might also be the cause. PMID- 11202058 TI - Potential health risks of radiofrequency fields from wireless telecommunication devices. PMID- 11202059 TI - Recent advances in research on radiofrequency fields and health. AB - Since the Royal Society of Canada report on potential health risks of radiofrequency (RF) fields from wireless telecommunications in the spring of 1999, there have been several newly published reports on risks associated with the use of mobile phones. This article provides a summary of scientific research on the potential health effects of radiofrequency fields that has been reported since the original Royal Society report was published. This update also discusses several earlier results not included in the original report. PMID- 11202060 TI - Vascular remodeling in experimentally induced subacute canine pulmonary hypertension. AB - We quantified in vivo pulmonary vascular remodeling in a large animal model of pulmonary hypertension (PH). In group PH (n = 6), 3 mg/kg dehydromonocrotaline (DHMC) was administered to 12-week-old beagles via a right atrial injection. Eight weeks after DHMC in group PH, pulmonary artery pressure increased significantly (P < .05) from 18 +/- 2 mm Hg at baseline to 30 +/- 4 mm Hg. Medial wall thickness and medial wall area as a percentage of total vessel diameter or area was significantly higher (P < .05) in group PH (29 +/- 9% and 48 +/- 12%) than in a control group (n = 5) (7 +/- 1% and 14 +/- 1%). Neointimal proliferation was observed in 42% of pulmonary arterioles in the PH group but never in the control group. We conclude that a single injection of DHMC in young beagles, in addition to the development of moderate degrees of PH after 8 weeks, causes significant pulmonary vascular remodeling, with features similar to those observed in patients with primary PH. PMID- 11202061 TI - Fetal androgen exposure inhibits fetal rat lung fibroblast lipid uptake and release. AB - Fetal lung fibroblasts provide lipid substrate for type II cell surfactant phospholipid synthesis. This process is developmental and glucocorticoid dependent. Previous studies in our laboratory demonstrating sex differences in several aspects of lung maturation suggest that these differences may be due to effects of fetal androgens. Based on these studies, we hypothesized that fetal lung fibroblast triglyceride metabolism is determined by opposing effects of fetal androgens and glucocorticoids. To model the effects of androgens on fetal lung fibroblast triglyceride metabolism, pregnant rats were treated with dihydrotestosterone (DHT) 1 mg/kg/day from the days 15 to 20 of gestation, and changes in triglyceride content of freshly isolated fetal rat lung fibroblasts (FRLF) and rates of uptake and prostaglandin E2 (PGE2)-mediated release by cultured FRLF in response to glucocorticoids in the presence or absence of DHT in vitro were measured. During lung development, the triglyceride content and rate of uptake of female-derived FRLF increased 3.5- and 4.8-fold, respectively, between days 18 and 20 of gestation. From days 19 to 22, male FRLF trigyclyceride content and rate of uptake were lower than the content and uptake by female FRLF. Maternal DHT treatment inhibited the normal developmental increase in fibroblast triglyceride content and rate of uptake between days 19 and 22 by both male and female FRLF. In the absence of maternal DHT, in vitro dexamethasone stimulated triglyceride uptake 3-fold by day 21 in FRLF. This effect was blocked by maternal pretreatment with DHT. Maternal DHT exposure prevented stimulation of triglyceride release by PGE2. Although in vitro dexamethasone stimulated triglyceride release by maternal DHT-exposed fibroblasts, it did not enhance the response to PGE2. These data suggest that in utero exposure to androgens (1) delay the developmental increase in triglyceride content and (2) oppose the effects of glucocorticoid on cultured FRLF triglyceride uptake and PGE2-mediated release. PMID- 11202062 TI - Influence of neuropeptides on neutrophil adhesion and transmigration through a lung fibroblast barrier in vitro. AB - The lung is richly supplied with peptidergic nerves that store and secrete substance P (SP), vasoactive intestinal peptide (VIP), and other neuropeptides known to potently modulate leukocyte function in vitro and airway inflammation in vivo. We examined the effect of SP, VIP and the novel sensory neuropeptide secretoneurin (SN), as well as of interleukin (IL)-8, IL-6, IL-1 beta, transforming growth factor (TGF)-beta, and tumor necrosis factor (TNF), all associated with acute lung injury, on human neutrophil migration across a 5-mu pore polycarbonate filter system covered by human lung fibroblast monolayers. Additionally, we tested the ability of these neuropeptides to elicit neutrophil adhesion to fibroblast monolayers. SP, but not VIP and SN, may be important in directly influencing neutrophil adhesion to and subsequent migration across a subendothelial barrier of fibroblasts and extracellular matrix towards lung inflammatory sites. The effect was mainly mediated by neurokinin (NK)-1 receptors, as evaluated by a specific NK-1 antagonist, [[(S,S)Pro-Leu(spiro-y lactam)]9,10, Trp11]substance P (1-11), whereas a specific NK-2 receptor antagonist, [Tyr5, D-Trp6,8,9, Lys10]neurokinin A (4-10), was ineffective. The SP analog septide and the NK-1 receptor agonist ([Sar9 Met(O2)11)SP were comparably effective. Furthermore, the SP effect was concentration and time dependent. However, the other tested neuropeptides might also affect neutrophil recruitment in inflammatory lung by modulating other lung cell functions. Additionally, all tested cytokines stimulated neutrophil transfibroblast migration in vitro, except IL-6. In conclusion, SP in concert with proinflammatory cytokines may regulate neutrophil interstitial accumulation and their traffic to the alveolar space in lung inflammation. PMID- 11202063 TI - Expression of lipoprotein receptor and apolipoprotein E genes by perinatal rat lipid-laden pulmonary fibroblasts. AB - Lipid-laden interstitial fibroblasts (LIFs) are abundant during alveolar septal formation in rats and accumulate droplets of neutral lipids. The mechanisms controlling lipid acquisition by LIFs are incompletely understood and accumulation varies during postnatal development, because lipid droplets are usually a transient phenotype. We hypothesized that plasma lipoproteins may be an important source of lipids and that the cells may alter their acquisition of lipoproteins by changing the expression of lipoprotein receptors and apolipoprotein E. We quantified the accumulation low-density lipoproteins (LDLs) and very-low-density lipoproteins (VLDLs) by LIFs and the expression of LDL and VLDL receptors mRNA and protein at various perinatal ages and found no significant age-related differences. Apolipoprotein E mRNA was maximal at postnatal day 15, whereas immunoreactive apolipoprotein E protein was maximal at gestational day 21, suggesting complex regulation. Our findings indicate that the age-related difference in the lipid droplet contents of LIFs is not primarily related to differences in LDL or VLDL receptor expression. They suggest that changes in the quantities of plasma lipoproteins, which are presented to LIFs in the lung at various perinatal ages, are more likely to be responsible for age related alterations in lipid droplet size and abundance. PMID- 11202064 TI - Phenotypic and functional differences between rat alveolar, pleural, and peritoneal macrophages. AB - Tissue macrophages (M phi) play a central and essential role in modulating the initiation and perpetuation of the inflammatory response. Phenotypical and functional differences among alveolar M phi (AM) and peritoneal M phi (PM) have been reported, but less is known about pleural M phi (PLM) and their ability and capacity to release biologically active substances. Therefore, the aim of this study was to determine the production of superoxide anion, nitric oxide (NO), and tumor necrosis factor alpha (TNF-alpha) by PLM in comparison to AM and PM in vitro. M phi from rats were isolated by lavage of the respective body compartment and characterized by evaluating the expression of the surface antigens MHC class II molecules, CD11b, and ED2-like antigen. Upon activation, AM produced significantly higher amounts of superoxide anion, NO, and TNF-alpha compared to PM and PLM. Taken together, the findings of this study demonstrate that rat PLM resemble PM more than AM in terms of production of key inflammatory mediators. PMID- 11202065 TI - Women's preferences for providers of and settings for Pap smears. AB - OBJECTIVE: To gauge women's flexibility in receiving Pap smears from someone other than their regular gynecologists, specifically, their general physicians. METHODS: A random sample of 500 English-speaking women members (age 18-80) of Kaiser Permanente completed a 20-minute telephone survey (72% response rate). Ten focus groups and 75 in-person interviews gathered qualitative information. RESULTS: Approximately half the surveyed women would see an unfamiliar gynecologist for a Pap smear (48%) and did not have a preference for the gender of the clinician (53%). Most women (72%) were open to seeing nurse practitioners if their regular gynecologists were not available. Although few women (26%) were initially positive about receiving Pap smears in their general medical clinics, half (45%) said they would prefer that to waiting for an appointment in gynecology. Interest was especially high (52%) among women with female rather than male internists or family practitioners (33%). CONCLUSIONS: Redesign efforts must emphasize choice in Pap smear delivery in order to increase convenience while respecting preferences for the existing system. PMID- 11202066 TI - Women in agriculture: risk and injury experiences on family farms. AB - OBJECTIVES: To determine the one-year incidence of nonfatal farm injuries among women actively engaged in farm work; to determine the distribution of these injuries by external cause, severity, and other characteristics; and to determine the potential risk factors for injuries among farm women. METHODS: A population based study of the occurrence of agricultural injuries during the previous year was conducted in a stratified, random sample of 1096 actively working farm women in Texas and Louisiana. Sampling pools were generated from county plat listings in Texas and maintained mailing lists in Louisiana; counties were selected based on geographical and agricultural diversity. Eligible women were interviewed by phone about injury occurrences and patterns. RESULTS: The cumulative one-year incidence of farm injuries for women in this area was 5% (95% CI = 3.7-6.3), based on the number of farm women injured. Lower extremities were the most frequently injured body parts. The leading external causes were contact with foreign object/substance, falls, and overdoing/lifting/hauling. Most injuries occurred in the summer or spring. Factors predictive of increased injury risk in adjusted logistic regression included working on large-animal farms, more time spent in farm work, persistent back pain or weakness during the previous 12 months, driving a tractor, and hauling farm goods to market. Most women consulted physicians as a result of their injuries. CONCLUSION: Physicians are in a unique position to institute interventions to prevent risky behaviors. PMID- 11202067 TI - Assessment of clinical partner violence screening tools. AB - OBJECTIVE: To compare the Women's Experience with Battering Scale (WEB) with the Index of Spouse Abuse-Physical Scale (ISA-P) as screening tools to identify intimate partner violence (IPV). METHODS: We conducted a large cross-sectional survey of women age 18 to 65 attending one of two family practice clinics from 1997 to 1998. All women completed both the WEB and the ISA-P and a telephone interview. We figured agreement estimates between the two tools, used stratified analyses to evaluate attributes of those more likely to screen as battered or physically assaulted, and compared associations between the WEB and ISA-P and a range of mental and physical health indicators known to be associated with IPV. RESULTS: 18% of 1152 eligible women surveyed had experienced IPV in a current or most recent intimate relationship with a male partner; 17% had been battered (WEB+), and 10% had been physically assaulted (ISA-P+). Had we used the ISA-P alone to assess IPV, we would have missed almost 45% of IPV. As anticipated, the ISA-P was more strongly associated with IPV-associated injuries and number of physician visits in the last year. The WEB was more strongly associated with self perceived mental health, anxiety, depression, drug abuse, and low social support. CONCLUSION: Clinicians need validated screening tools to rapidly and reliably screen patients for IPV. Most screening tools assess physical violence and injury without considering the more chronic experience of battering and the psychological terror associated with this violence. The WEB may identify more abused women than tools measuring physical assaults. PMID- 11202068 TI - Syphilis elimination: a unique time in history. PMID- 11202069 TI - Implementing the Institute of Medicine report on lesbian health. AB - The Institute of Medicine (IOM) recently published the report of its committee on lesbian health research priorities, which concluded that there has been little emphasis on and funding for research on the health of lesbians, despite the increased emphasis on women's health research in the 1990s. The report recommended additional research to determine if lesbians are at higher (or lower) risk for certain health problems than other women. It noted significant barriers to conducting lesbian health research, including lack of funding and several methodological issues. The IOM anticipates that the research recommended will benefit other populations as well. Several federal agencies in the Department of Health and Human Services can provide technical expertise and support to implement the report's recommendations, and suggestions are given here. The IOM report legitimizes scientific investigation into lesbian health, which should increase public and private research funding and the number of researchers in this area. A paradigm shift for lesbian health research is on the horizon, and we are grateful to the dedicated cadre of researchers, both published and unpublished, who have pioneered and persisted in this research during the past 25 years. PMID- 11202070 TI - Substance abuse and mental illness: unaddressed public health issues for women. AB - Although women have been disproportionately affected by substance abuse and mental illness, these issues have received little attention. Women with substance abuse and mental disorders tend to experience more severe environmental, health, social, and economic consequences and require more costly care. The Substance Abuse and Mental Health Services Administration is responsible for strengthening the nation's health care delivery system for prevention and treatment of substance abuse and mental illness and addresses women's issues through its Women, Children, and Families Team (WCFT). The WCFT is concerned with the public health risks associated with substance abuse and mental disorders in women, including physical and sexual abuse/violence, human immunodeficiency virus and acquired immune deficiency syndrome, criminal justice, welfare reform, and child welfare. PMID- 11202071 TI - Women and HIV: creating an ambiance of caring. AB - In their study of women living with or at risk of human immunodeficiency virus (HIV) infection, Schuman et al found that one-third of women reported needing mental health care, but that only two-thirds of those in need had that need met. This article describes an approach to providing mental health services to women with HIV used in our Chicago clinic. What we call the "ambiance of caring" creates an atmosphere in which mental health support can be provided and received. A continuing respectful primary care relationship and a supportive non judgmental environment are the keys to success. Good communication, sensitive history taking, appropriate assessment tools, and direct questioning in a safe setting will let the patient know that you really care about what she is experiencing. Real-time referrals with a team of social workers, psychologists, and psychiatrists allow the best beginning to the therapeutic relationship. The next decade will provide an opportunity to address the mental health concerns of women with HIV--some of our society's most complex patients. PMID- 11202072 TI - [AIDS and anesthesia: mutual risks] . PMID- 11202073 TI - [Aids and anesthesia] . AB - 17 years after the discovery of HIV Aids remains an ultimately fatal disease. Currently no vaccine is available. The worldwide incidence of HIV-infections and Aids associated mortality are rising. Only in Western Europe and in the USA are incidence and mortality of Aids declining; mainly as a result of effective antiretroviral therapy. 20% to 25% of HIV-infected patients require surgery during their illness. The challenges for the anaesthesiologist are possible dysfunction of all important organs and adverse interactions between antiretroviral drugs and anaesthetic agents. If adequate infection control measures are taken the risk of occupational HIV-infection is low, but remains a concern in light of the consequences. Seroconversion after needlestick injury is ca. 0.3%, after contact with mucosa ca. 0.03%. PMID- 11202074 TI - [The effect of air within the infusion syringe on drug delivery of syringe pump infusion systems] . AB - Application of highly concentrated short-acting vasoactive drugs in the critically ill patient requires precisely working syringe pump systems for continuous intravenous drug delivery. We performed a bench study to investigate the consequences of small amounts of air entrapped within a 50-ml infusion syringe. In particular we studied the effect of entrapped air on drug delivery after moderate vertical displacement of the pump by 50 cm (e.g. in preparation for transport) and the effect on the time required to trigger the pressure alarm after occlusion of the infusion line. At a flow rate of 1 ml/h, lowering the syringe pump prolonged the zero-drug delivery time from (mean +/- SD) 4.1 +/- 0.8 min (without air) to 6.2 +/- 0.9 (with 1 ml air) and to 13.1 +/- 0.9 min (with 2 ml of air, p < 0.001 for all comparisons). Entrapping of 2 ml of air within the syringe resulted in a 2.6-fold prolongation of the occlusion alarm time after accidental occlusion of the infusion line and a 3-fold increase of the resulting infusion bolus after occlusion. Enclosed air within infusion syringes considerably affects the syringe compliance. It increases the susceptibility of constant drug delivery to vertical displacement of syringe pumps and impairs the occlusion alarm function. Therefore, any air in syringe of infusion pump systems should be carefully removed. To avoid infusion boluses of short-acting vasoactive drugs after accidental occlusions, the occluded infusion line should be released to ambient pressure first. PMID- 11202075 TI - [Patient-oriented anesthesia] . AB - Goals of this study were to quantify patients' preferences for anaesthesia care and to identify what they know about various tasks of an anaesthetist. On the day before surgery, 122 patients scheduled for elective procedures were interviewed using a structured questionnaire. A reliable pain relieve and unawareness as well as stable vital functions have priority in patients' preferences. Patients are also concerned with good postoperative pain relieve and the avoidance of nausea and vomiting. Not important are short preoperative soberness, rapid awakening and initial wide awakeness. Not informed about typical tasks of an anaesthetist are 28-51% of the patients. In order to obtain maximum patient satisfaction, a thorough education plus further continuous training are the essential items for a patient orientated health care management in anaesthesia, along with good medical and technical equipment. The wide spectrum of tasks of an anaesthetist must be better represented in order to strengthen the position of anaesthesia in the competition for rare resources. A postoperative visit, which is judged of 77% of the patients as important, offers a beginning. PMID- 11202076 TI - [Unilateral phrenic nerve paralysis after vertical infraclavicular plexus block] . AB - We present a case of a rapid onset reversible phrenic nerve block following vertical infraclavicular blockade of the brachial plexus. Five minutes after injection of local anaesthetics the SpO2 fell to 80%. Oxygen supplementation was required during the perioperative period to maintain normoxemia. The postoperative X-ray showed an elevated diaphragm of the ipsilateral side. After five hours oxygen supply could be terminated, an X-ray control the next day showed normal bilateral diaphragm position. PMID- 11202077 TI - [Fulminant pulmonary embolism after cesarean section]. AB - On the first day after an uneventful emergence caesarean section a 36-year-old woman developed circulatory collapse requiring cardiopulmonary resuscitation for 15 minutes. After resuscitation the patient remained haemodynamically unstable and was clinically highly suspected to suffer from fulminant pulmonary embolism. In this situation the physicians caring for the patient decided to perform a surgical pulmonary embolectomy without previous diagnostic workup. Massive emboli were removed from both pulmonary arteries. Postoperatively the patient recovered and was transferred to a rehabilitation center without severe cerebral sequelae. PMID- 11202078 TI - [The historical development of intensive care in Germany. Contemporary views. 20. The limits of intensive care--economic and ethical limits] . PMID- 11202079 TI - [The historical development of intensive care in Germany. Epilogue to a thematic review in Der Anaesthesist] . PMID- 11202080 TI - [Continuous or discontinuous monitoring of sedation in the intensive care unit? The effects of daily interruptions of sedation monioring in respirator patients] . PMID- 11202081 TI - [The Nobel Prize for Medicine 2000. Communicating nerve cells] . PMID- 11202082 TI - [Catecholamine therapy in sepsis] . PMID- 11202083 TI - [Thromboembolytic complications. Alternative anticoagulation in HIT II]. PMID- 11202084 TI - Audit of treatment by radiotherapy of carcinoma of the cervix in the UK in 1993: worse than expected results. PMID- 11202085 TI - Morbidity in radiotherapy practice. PMID- 11202087 TI - Cervical carcinoma recurring in an abdominal wall incision. AB - Incisional recurrence of carcinoma of the uterine cervix is very rare. We report two patients who developed recurrence in the abdominal wall incision after hysterectomy. The first patient was aged 60 years and had a FIGO Stage IB1 cervical carcinoma treated initially by Wertheim's hysterectomy and postoperative radiotherapy. Nine months after surgery she developed recurrence on the abdominal scar, which was outside the radiation portal. She was treated with electron beam radiation therapy. The second patient developed an incisional recurrence 23 months after surgery and was treated by wide excision of the mass followed by radiotherapy. A survey of the literature identified 12 reported cases to date (eight squamous cell carcinoma and four adenocarcinoma). PMID- 11202086 TI - National audit of the management and outcome of carcinoma of the cervix treated with radiotherapy in 1993. AB - The aim of the study was to investigate the UK prevalence of late, severe side effects associated with radical radiotherapy for cancer of the cervix and try to identify associated factors. All patients treated for cancer of the cervix with radical radiotherapy in 1993 were identified and retrospective case notes studied to determine mortality and severe complications occurring following treatment. Of the 55 radiotherapy departments in the UK that were treating gynaecological malignancy in 1993, 53 participated in the study. There were 1558 patients with carcinoma of the cervix receiving radical radiotherapy as part of their treatment regimen in 1993, whose patterns of treatment were assessed. The main outcome measures were the development of late severe complications as defined by the Franco-Italian Glossary and mortality. Of the patients receiving surgery and radiotherapy, 58.5% underwent Wertheim's procedure. The crude rate of late severe complications in all patients with cervical cancer treated with radical radiotherapy in 1993 was 6.1% (actuarial rate 8%) at 5 years, and only four of the 91 patients who developed complications died as a result of their morbidity. There was no significant correlation of stage, centre size, surgery or radiotherapeutic approach with late morbidity in univariate analysis. The overall survival at 5 years was 47% and was lower than that of the European data from FIGO's 1990-92 cohort, for all stages. Increasing FIGO stage was the only factor significantly associated with mortality. The absence of variables that were significantly associated with late complications may well be related to the relatively low event rate compared to the sample size. Differences in surgical treatment prior to radiotherapy and radiation technique may be confounding the comparison of outcomes. The relatively poor survival for locally advanced disease and the difficulty with which these data were collated indicates that national prospective data collection is urgently required to monitor performance and hence derive best practice. PMID- 11202088 TI - Neuroendocrine small cell carcinoma of the uterine cervix: what disease? What treatment? Report of ten cases and a review of the literature. AB - Neuroendocrine small cell carcinoma of the uterine cervix (NESCCC) is an entity with very aggressive behaviour. The optimal initial therapeutic approach to this rare disease has not yet been clearly defined. We reviewed our experience of this disease over the past 10 years with regard to chemosensitivity. Since 1988, ten patients (mean age 33 years; range 24-47) have been diagnosed with NESCCC and treated in our institutions. Disease stage at presentation was IA (one), IB (five, two with lymph node involvement), IIB (one), IIIB (one), and IV (two). One patient had metastatic disease at presentation; three developed metastases during initial treatment. Eight patients underwent surgery and eight received radiation therapy. Six patients received pre- or postoperative cisplatinumvepeside (PE) combination chemotherapy, either alone or concurrently with radiation therapy. PE alone as primary chemotherapy led to disease stabilization in the two patients so treated; concurrent PE and radiation therapy resulted in a pathological complete response in one patient. Eight patients relapsed within 16 months and died of their disease within 29 months from the initial diagnosis. Two patients are alive with no evidence of disease at 13 and 53 months. Our series confirms the previously described very poor prognosis of NESCCC, despite initial aggressive multidisciplinary treatment. It may be that the introduction of chemotherapy, especially combined primary chemoradiotherapy, might allow patients to do a little better, although at the moment there is no good evidence one way or the other. PMID- 11202089 TI - Optimizing the management of differentiated thyroid cancer. PMID- 11202090 TI - Radioiodine treatment for differentiated thyroid cancer. PMID- 11202091 TI - Northern Cancer Network guidelines for management of thyroid cancer. PMID- 11202092 TI - A pilot study of postoperative CHART and CHARTWEL in head and neck cancer. AB - A Phase II pilot study of continuous hyperfractionated accelerated radiotherapy (CHART)/CHART weekend less (CHARTWEL) was carried out in the postoperative treatment of patients with squamous cell carcinoma of the head and neck. Twenty four patients (17 male, seven female) with a median age of 64 years (range 34-80) were treated with postoperative radiotherapy between 1991 and 1999. All patients presented with primary squamous cell carcinoma, which, at surgery, had shown adverse pathological factors for recurrence. Intermediate risk was determined by the presence of two of the following factors: margins 5 mm, Stage T3/T4, perineural or vascular invasion, poor differentiation, oral primary, multicentric primary, and more than four positive lymph nodes. High-risk factors included the presence of extracapsular spread and/or incomplete resection margins, or the presence of four of the factors defining intermediate risk. The patients were treated using a CHART (n = 11) or a CHARTWEL (n = 13) schedule, administering a dose between 49.5 Gy and 54 Gy. High-risk factors were present in 18/24 patients. Treatment was commenced from a median time of 6.9 weeks (range 4.4-16.6) after radical surgery. All patients completed treatment. A confluent radiation mucositis occurred in 20/23 evaluable patients, which settled in 4-10 weeks after commencing radiotherapy. Moderate dysphagia was observed in 13 patients. Mild subcutaneus oedema was noted in 11 patients from 12 weeks after treatment. No significant late toxicity has been observed. Over a median follow up-period of 17 months, local control has been maintained in 17 patients (71%). Seven patients have relapsed and died of disease. A mean survival of 24 months (range 1-84) has been observed. This pilot study demonstrates acceptable morbidity for CHART/CHARTWEL in the postoperative setting. A prospective multicentre randomized trial using an accelerated schedule of radiotherapy versus conventional fractionation for the radical postoperative treatment of primary head and neck cancer is currently in preparation. PMID- 11202093 TI - Paranasopharyngeal space involvement in nasopharyngeal cancer: detection by CT and MRI. AB - Paranasopharyngeal tumour extension (PTE) from nasopharyngeal carcinoma (NPC) is staged in its own subgroup in the American Joint Committee on Cancer classification. Most large clinical trials use computed tomography (CT) to stage PTE, but diagnosis relies on indirect signs of tumour invasion such as asymmetry of the parapharyngeal fat. Magnetic resonance imaging (MRI) has the advantage of directly revealing PTE because of its ability to depict the complex anatomical structures that form the boundary of the nasopharynx. The aim of this study was to compare CT and MRI in the identification of PTE and to determine whether the imaging modality used influenced staging of the disease. The MRI and CT scans of 78 patients (156 parapharyngeal regions) with NPC were assessed for PTE. On MRI, PTE was considered to be positive when there was tumour invasion through the complex anatomical structures of the nasopharyngeal wall. When using CT, it was considered positive when there was: (1) distortion of the parapharyngeal fat plane; or (2) extension beyond a line drawn from the medial pterygoid plate to the lateral aspect of the carotid artery. CT scanning and MRI were compared. PTE was judged to be present in 28 of 78 (36%) patients by MRI and in 41 of 78 (53%) scanning by CT when using criterion 1 or 2. An analysis of the discordant findings revealed that MRI was positive in three sides of the nasopharynx in early tumour extension through the pharyngobasilar fascia but not identified with CT by using criterion 1 or 2. MRI was negative in 20 and 21 sides of the nasopharynx that were judged to be positive on CT by using criterion 1 and 2 respectively. In these patients MRI revealed that the positive CT scan was caused by a large tumour compressing but not invading the parapharyngeal fat space, a metastatic lateral retropharyngeal node, or a combination of the two. The imaging modality used for staging NPC has an impact on the staging of PTE. CT scanning suggested the presence of PTE more frequently than MRI because of its inability to distinguish the primary tumour from lateral retropharyngeal nodes, and direct tumour invasion of the parapharyngeal region from tumour compression. The imaging modality and criteria used for staging PTE should be taken into consideration when assessing the results of clinical studies. PMID- 11202094 TI - Late radiation side-effects in three patients undergoing parotid irradiation for benign disease. AB - We report three patients in whom standard radiation therapy was given and serious late radiation damage was seen. The first patient suffered recurrent parotiditis and a parotid fistula. He was treated initially with 20 Gy in ten fractions via a 300 kV field. Further irradiation was required 1 year later and 40 Gy was given in 2 Gy fractions by an oblique anterior and posterior wedged photon pair. Ten years later he developed localized temporal bone necrosis. The second patient, with pleomorphic salivary adenoma, developed localized temporal bone necrosis 6 years after 60 Gy had been given using standard fractionation and technique. The third patient received 55 Gy in 25 fractions for a pleomorphic salivary adenoma and after 3 years developed temporal bone necrosis. Sixteen years later the same patient developed cerebellar and brainstem necrosis. All patients developed chronic persistent infection during or shortly after the radiation therapy, which increased local tissue sensitivity to late radiation damage. As a result, severe bone, cerebellar and brainstem necrosis was observed at doses that are normally considered safe. We therefore strongly recommend that any infection in a proposed irradiated area should be treated aggressively, with surgical debridement if necessary, before radiotherapy is administered, or that infection developing during or after irradiation is treated promptly. PMID- 11202095 TI - Carotid sinus syndrome secondary to head and neck malignancy: case report and literature review. AB - We report two cases of carotid sinus syndrome secondary to head and neck malignancy. The underlying mechanisms unique to head and neck malignancy and treatments of the syndrome are discussed. PMID- 11202096 TI - Brachial plexus traction injury following axillary node dissection. PMID- 11202097 TI - United Kingdom Radiation Oncology 1 Conference (UKRO 1), York, 23-25 April 2001. PMID- 11202098 TI - Posttraumatic stress disorder in children after the military operation "Anfal" in Iraqi Kurdistan. AB - Five years after the military operation "Anfal" in Iraqi Kurdistan, 45 families were randomly selected among the survivors in two displacement camps. The Posttraumatic Stress Symptoms for Children (PTSS-C) and the Harvard Trauma Questionnaire (HTQ) were administered to the oldest child and the caregiver in each family, respectively. Posttraumatic stress disorder (PTSD) was reported in 87% of children and 60% of their caregivers. While childhood PTSD was only significantly predicted by child trauma score and the duration of captivity, it was neither predicted by maternal PTSD nor did it disappear after the reunion with the PTSD-free father. However, the small sample size makes the results hypotheses rather than conclusive. PMID- 11202099 TI - Adolescents hospitalised with deliberate self-harm: the significance of an intention to die. AB - All suicide attempters admitted to medical wards in the greater Oslo area, (n = 91) aged 13-19 years, were dichotomised on the basis of one item in the Motives for Parasuicide Questionnaire (MPQ) and one item in the Suicide Intent Scale (SIS): if the intent was to die (n = 57), or not (n = 34). The two groups were compared regarding the attempt, mental health problems, and psychosocial risk factors. The attempt of adolescents with an intent to die were more serious, rated with SIS (15.7 vs. 5.7, p < 0.001), with Risk Rescue Rating (p = 0.003) or rated medically (p < 0.05). They were clinically more often depressed (61% vs. 32%, p < 0.01), felt more hopeless (Hopelessness Scale) (10.8 vs. 8.2, p < 0.05), were less disruptive (11% vs. 32%, p < 0.05) and less often abused substances (0 vs. 12%, p < 0.05). Both groups were equally burdened with other factors. Differentiation on the basis of suicidal intent delineated two groups, both with considerable psychosocial problems. Those with suicide intent had more internalising problems including depression, while those with other intents showed more externalising behaviour. The need for help in the group with no intent to die may be underestimated. PMID- 11202100 TI - Using DSM diagnoses for clinical, research, and administrative purposes. AB - DSM data are often used to build statistics on the types of patients to whom mental health services are offered. These statistics are normally based on broad categories that cluster finer subcategories for specific diagnoses. These broad categories can be built in a number of ways. The purpose of this study is to determine the effect of the choices made in forming broad DSM categories, by observing the resulting differences in clinical health statistics. Results based on 3496 clinical cases show that DSM-III-(R) classifications can be presented in different formats, leading to different outcomes. To avoid wrong conclusions based on one format, DSM statistics should always be presented in varying formats. PMID- 11202101 TI - Have the Cross-Informant Syndromes of the CBCL any practical value in identifying grouped ICD10 diagnoses? AB - 120 children referred to a child and adolescent psychiatric service in a university clinic were studied with the aim of deriving predictors for grouped ICD10 diagnoses using the CBCL Cross-Informant-Syndromes (CISs). CIS7 (Delinquent Behaviour) and CIS8 (Aggressive Behaviour) were shown to significantly separate Disruptive Behaviour Disorders from all other disorders. As cross-validation, a separate clinical sample of 118 children from a similar service in another part of the country was used to see to what extent the CIS predictors from the first sample held up in the second sample. Positive and Negative Predictive Powers, all corrected for chance, confirmed that the Disruptive Behaviour Disorder group could be usefully separated from all other disorders using the Delinquent Behaviour and the Aggressive Behaviour Cross-Informant Syndrome scores. There was no good evidence that Emotional (Anxiety-Mood) Disturbance could be usefully separated in the same way using the Anxious-Depressed Syndrome (CIS3) or any other syndrome. Discriminant Function Analysis showed that there was no significant improvement in prediction when more elaborate linear combinations of the syndromes were used. PMID- 11202102 TI - Comparing the German versions of the Strengths and Difficulties Questionnaire (SDQ-Deu) and the Child Behavior Checklist. AB - The Strengths and Difficulties Questionnaire (SDQ) is a brief behavioural screening questionnaire that can be completed in about 5 minutes by the parents and teachers of 4-16 year olds. The scores of the English version correlate well with those of the considerably longer Child Behavior Checklist (CBCL). The present study compares the German versions of the questionnaires. Both SDQ and CBCL were completed by the parents of 273 children drawn from psychiatric clinics (N = 163) and from a community sample (N = 110). The children from the community sample also filled in the SDQ self-report and the Youth Self Report (YSR). The children from the clinic sample received an ICD-10 diagnosis if applicable. Scores from the parent and self-rated SDQ and CBCL/YSR were highly correlated and equally able to distinguish between the community and clinic samples, with the SDQ showing significantly better results regarding the total scores. They were also equally able to distinguish between disorders within the clinic sample, the only significant difference being that the SDQ was better able to differentiate between children with and without hyperactivity-inattention. The study shows that like the English originals, the SDQ-Deu and the German CBCL are equally valid for most clinical and research purposes. PMID- 11202103 TI - The Strengths and Difficulties Questionnaire among Finnish school-aged children and adolescents. AB - The emotional and behavioural problems of 7- to 15-year-old Finnish children and adolescents (n = 735) were assessed in a community population by a brief screening instrument, the Strengths and Difficulties Questionnaire (SDQ). The parent-, teacher- and self-reports of the SDQ were obtained. The results show that for the total scores, the inter-rater agreement between the pairs of reports was 0.38-0.44. The internal consistency in all three questionnaires was 0.71. Functioning above the 90th percentile of the SDQ total difficulties scores in parent-, teacher- and self-reports was strongly associated with help-seeking variables and problematic behaviour according to parents. The correlation of the parental SDQ total scores and the Child Behaviour Checklist total scores was 0.75 and the correlation of the self-report SDQ total scores with the Youth Self Report total scores was 0.71. The differences in sex, grade and informants of the SDQ total difficulties scores are reported. The study gives further evidence of the usefulness of the SDQ as a promising screening instrument for epidemiological research and clinical purposes. PMID- 11202104 TI - Reliability and validity of a child-specific cross-cultural instrument for assessing posttraumatic stress disorder. AB - The Posttraumatic Stress Symptoms in Children (PTSS-C) was developed as a cross cultural semi-structured interview to diagnose posttraumatic stress disorder (PTSD) and to identify PTSD-non-related posttraumatic stress symptoms in children after various traumatic experiences. The psychometric properties were studied in two different child populations in Iraqi Kurdistan (the survivors of the military operation "Anfal", and the orphans), in a sample of Kurdistanian refugee children in Sweden, and in a comparison sample of Swedish children. The instrument yielded satisfactory internal consistency, high interrater agreement, and excellent validity on cross-validation with the Child Posttraumatic Stress Disorder Reaction Index (CPTSD-RI) and the Diagnostic Interview for Children and Adolescents (DICA) according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). PMID- 11202105 TI - Diagnostic assessment of communicative and interactive behaviours in children with autism and receptive language disorder. AB - Children with autism and children with a severe specific receptive language disorder both show clear deficits in communicative language skills and in social relationships. In this study the usefulness of the Autism Diagnostic Observation Schedule (ADOS) in the differential diagnosis between these two groups of developmentally impaired children is assessed. 11 children with early infantile autism and 20 children with a specific receptive language disorder participated in the study. 18 children with an expressive language disorder were used as a control group. The ADOS was individually administered to all children by the same examiner. The results showed that on most of the ADOS measures the autistic children were clearly more deviant than the language impaired children. There were no significant differences between the two groups of language impaired children. Eight out of 11 autistic children reached the defined cut-off values on the measures "language and communication" and "social interaction" of the ADOS algorithm, whereas only three autistic children did so on the measure "stereotyped behaviour". None of the language-impaired children reached the cut off values on more than one measure. The ADOS allowed for good assessment of certain types of behaviour. However, to confirm the diagnosis of infantile autism, additional information from parents is required. PMID- 11202106 TI - Severely disturbed children's human figure drawings: are they unusual or just poor drawings? AB - Previous research has shown that the human figure drawings of severely disturbed children contain more emotional indicators than those of well-adjusted children, whether the well-adjusted children are of the same chronological age or are younger but of the same mental age as the severely disturbed children. This finding suggests that the disturbed children's drawings may be different rather than merely immature. A problem with previous research, however, is that groups have not been matched for drawing ability. In study 1 of this paper each drawing of 44 severely disturbed boys was matched with that of a normal boy according to its score on the Goodenough-Harris scoring system. There was no significant difference between the groups in the number of emotional indicators included in the drawings. Furthermore, in study 2, judges could not discriminate the drawings of the two groups. It was concluded that the differences noted in previous research were most likely due to the poorer drawing ability of the severely disturbed children rather than unusual features in their drawings. PMID- 11202107 TI - Case report: autistic disorder and chromosomal abnormality 46, XX duplication (4) p12-p13. AB - We report an 18-year-old female with a diagnosis of DSM-IV Autistic Disorder and moderate to severe mental retardation who was discovered to have a previously undescribed chromosomal abnormality 46, XX, duplication (4) p12-p13. We discuss her history and diagnosis, noting that the co-occurrence of her diagnoses have not previously been documented. The report adds to the literature supporting the argument that individuals with autistic spectrum disorders should be re-examined for chromosomal abnormalities. PMID- 11202108 TI - Stimulants in AD/HD, a controversial treatment only in Sweden? PMID- 11202109 TI - Diagnosis: a Janeway lesion and an Osler's node. PMID- 11202110 TI - Value of standard laboratory tests for the early recognition of group A beta hemolytic streptococcal necrotizing fasciitis. AB - The laboratory data for 17 patients with group A beta-hemolytic streptococcal necrotizing fasciitis (GAS NF) were compared with data for 145 patients hospitalized for cellulitis during the same period. Admission values of C reactive protein and creatine kinase were higher for patients in the group with GAS NF than for patients in the group with cellulitis (P<.001), suggesting that standard laboratory tests may be useful for the early differential diagnosis of GAS NF and cellulitis. PMID- 11202111 TI - Intervene more often, evaluate more carefully, build on what works. PMID- 11202112 TI - Effectiveness of the Indiana 4-H tractor program at instilling safe tractor operating behaviors and attitudes in youth. AB - The purpose of this research was to determine what impact the Indiana 4-H Tractor Program has had on safer tractor operating behavior and attitudes of participants and to provide recommendations for program improvement. To assess the impact, 108 non 4-H youth who reported they operated a tractor regularly were compared with 104 4-H Tractor Program participants. A single skilled evaluator observed each individual in the two groups as she/he operated a tractor through a standard tractor-operating course. Information on recent tractor-related injury history and attitudes toward tractor safety was gathered using a written survey. Results showed that the program has had both a perceived and demonstrable positive influence; however, a need for improvements was also shown. Most significant of the findings was that participants in the 4-H Tractor Program were observed to operate tractors in a safer and more skillful manner. Even though the 4-H Tractor Program participants reported substantially more exposure time to tractor operation, they did not report a significantly different injury experience in comparison to the non-participants. Responses from the 4-H program participants, however, indicated a trend toward having more tractor-related close call incidents. There was no significant difference between the two groups in their attitudes toward tractor safety. Program recommendations developed as a result of the study primarily related to the need for updating instructional material used in the 4-H Tractor Program and the need for additional training and resources for volunteer leaders. PMID- 11202113 TI - Job hazards for musculoskeletal disorders for youth working on farms. AB - A series of eight focus groups were convened to: (1) identify tasks and activities performed by youth on farms with the potential for causing non traumatic work-related Musculoskeletal Disorders (MSDs); (2) determine the participants perceptions about risks of MSDs for youths performing those tasks; and (3) determine other factors that might relate to MSDs for youth working on farms, such as possible interventions for prevention. Seventy-two farm family members, 40 adults and 32 farm youth aged 8-18, participated in focus groups. Ten questions were posed to each of the eight groups about what tasks youth perform on the farm, how the work is assigned, and what risk factors are associated with the work. There was general agreement among the adults that maturity rather than age is the dominant factor for determining what tasks are performed by youth workers on the farm. Youth, on the other hand, believed that task urgency dictated what jobs were assigned to youth workers. Most adults indicated that lifting objects, forking, or shoveling was responsible for most of the serious non-traumatic injuries. Bending over while working, sitting in an awkward position looking back at equipment from a tractor, sitting in a cramped position, looking down at a combine header, and long hours of work were also identified as potential problems. Youth described muscle aches and strains of the legs, arms, shoulder, back or neck as everyday occurrences. According to the youth, "If it's not broken, you're fine". Only basic training is provided and most respondents believed that youth learned best through observation. There was general agreement that physician recommended guidelines for assigning youth to tasks would be ignored unless they carried the force of the law. PMID- 11202114 TI - The perception of farm safety and prevention issues among the Old Order Amish in Lancaster County, Pennsylvania. AB - The purpose of this study was to explore farm safety and prevention issues within an Old Order Amish community. A qualitative ethnographic approach was used to explore perceptions of Amish adults as to the issues related to farm safety and prevention for their children. Access to this community was facilitated through two contact people who were well known in the community. Data were collected using semistructured interviews and recorded as field notes. Data analysis was done by looking for themes based on the questions asked about safety and prevention. From this analysis, four themes were found related to safety and prevention. They included education of the parents, education of the children, home and farm preventive measures, and enforcement of established rules. In addition, childhood readiness was found to be another important issue related to farm safety. Childhood readiness was found to have three themes, developmental appropriateness, parental control and supervision, and birth order of the child. Data from this study suggested that farm safety is a concern of the Old Order Amish in Lancaster County. Their perceptions of safety and prevention issues centered on the incidents that have occurred and are considered dangerous. It is important to look at the identified safety and prevention and childhood readiness themes to identify the most beneficial approaches for the Amish to promote safety on their farms. PMID- 11202115 TI - Finite element modeling of ROPS in static testing and rear overturns. AB - Even with the technological advances of the last several decades, agricultural production remains one of the most hazardous occupations in the United States. Death due to tractor rollover is a prime contributor to this hazard. Standards for rollover protective structures (ROPS) performance and certification have been developed by groups such as the Society of Automotive Engineers (SAE) and the American Society of Agricultural Engineers (ASAE) to combat these problems. The current ROPS certification standard, SAE J2194, requires either a dynamic or static testing sequence or both. Although some ROPS manufacturers perform both the dynamic and static phases of SAE J2194 testing, it is possible for a ROPS to be certified for field operation using static testing alone. This research compared ROPS deformation response from a simulated SAE J2194 static loading sequence to ROPS deformation response as a result of a simulated rearward tractor rollover. Finite element analysis techniques for plastic deformation were used to simulate both the static and dynamic rear rollover scenarios. Stress results from the rear rollover model were compared to results from simulated static testing per SAE J2194. Maximum stress values from simulated rear rollovers exceeded maximum stress values recorded during simulated static testing for half of the elements comprising the uprights. In the worst case, the static model underpredicts dynamic model results by approximately 7%. In the best case, the static model overpredicts dynamic model results by approximately 32%. These results suggest the need for additional experimental work to characterize ROPS stress levels during staged overturns and during testing according to the SAE standard. PMID- 11202116 TI - [Investigation of the cerebral projection of the vestibular system using positron emission tomography]. AB - The authors investigated the cerebral projection of the vestibular system, using positron emission tomography, in right-handed subjects. Both sided cold caloric stimulation was used in every volunteer (n = 6). A detailed map of activated and deactivated brain regions is included. This portrays changes caused by vestibular stimulation. The contralaterally activated regions according to the stimulation side were: postcentral gyrus, transvers temporal gyrus, superior temporal gyrus, posterior part of the insula, claustrum, putamen, inferior parietal lobule, precentral gyrus, premotor cortex, cingulate gyrus. The ipsilaterally activated regions were: transvers temporal gyrus, superior temporal gyrus, inferior parietal lobule, posterior part of the insula. There was no hemispherial dominance. The activated regions partially correspond with previous results in the literature. It would like to be pointed out the Brodmann 6 region as the cortical manifestation of involuntary isometric tightening of muscles. The contralaterally deactivated regions were: inferior, superior and medius temporal gyrus, medial and medius frontal gyrus, inferior occipital gyrus, parahippocampal gyrus and hippocampus. Ipsilaterally deactivated regions were: superior and medial frontal gyrus, inferior temporal gyrus, angular gyrus, parahippocampal gyrus and hippocampus, fusiform and inferior occipital gyrus. There was prominent hemispherial dominance in the stimulated, ipsilateral side. The deactivation based functional connection between the hippocampus and the vestibular system was pointed out in such a relation for the first time in this report. PMID- 11202117 TI - [Increase in prevalence of childhood asthma in Budapest in relation to the air pollution data and the total pollen count]. AB - The authors surveyed the prevalence of bronchial asthma in childhood in Budapest in 1995 and in February 1999, via questionnaires directed to paediatricians. In 1995, replies were received from 118 paediatricians in 11 districts, who were responsible for the supervision of 104,087 children, of these, 1.88 +/- 0.87% had been diagnosed as having asthma. In 1999, replies were sent by 153 physicians in 22 of the 23 districts, who had a total of 142,684 children under their care. These included 3228 asthmatics, i.e. a prevalence of 2.26 +/- 0.95%. The difference between the two data was highly significant (p = 0.0001). The prevalence increased by 20% in 4 years. The dust, CO, NO2 and SO2 concentrations in the air were measured constantly at 8 points in Budapest, while ozone level measurements were also made at 2 stations. The counts of pollens and of fungal elements in the air were calculated separately for Buda and for Pest. These data overall revealed that the level of air pollution in Budapest did not deteriorate in the period in question, and the pollen counts from allergizing plants did not rise relative to earlier years. An interesting question (though it is far from certain that this is a causal correlation) can be upposed whether the 13% drop in the number of live births in Hungary during this 4-year period can be connected with the 20% rise in prevalence of childhood asthma. PMID- 11202118 TI - [Comparative analysis of clinical and laboratory charactiristics of antiphospholipid syndrome]. AB - The authors detected lupus anticoagulant and/or anticardiolipin antibodies in 1519 patients' blood samples between 1986-1999 in 3rd Department of Internal Medicine of Medical School of Debrecen. Examining only the proved thrombotic events and fetal losses as symptoms of antiphospholipid syndrome 218 patients had suffered from this syndrome. Secunder antiphospholipid syndrome was the diagnosis in case of 420 patients, the most common in Systemic Lupus Erythematosus (288 patients). In 704 antiphospholipid antibody positivity cases the diagnosis of antiphospholipid syndrome was not fulfilled. Analysing the antibodies profile of primary and secondary antiphospholipid syndrome in SLE, IgG type anticardiolipin antibody positivity was significantly higher in blood samples of SLE patients (82 patients, p < 0.01). Among thrombotic manifestations of antiphospholipid syndrome cerebrovascular thrombosis were significantly higher in patients suffering from SLE (128 patients, p < 0.04), while the occurrence of venous thrombosis, thrombosis of coronary, carotic, aorta and peripheral arteries and recurrent abortions was not significantly different in case of primary and secondary antiphospholipid syndrome. Lupus anticoagulant positivity means higher risk for venous thrombosis (94 patients, p < 0.0001), but anticardiolipin antibody positivity associated with a higher risk for thrombosis of coronary, carotic, aorta and peripheral arteries (59 patients, p < 0.00006). Comparing IgG- and IgM type anticardiolipin antibody positivity the authors found significantly higher cerebrovascular thrombosis events in IgG-anticardiolipin group (p < 0.004). Sneddon syndrome were detected in 17 patients in the primary antiphospholipid syndrome group and in 16 cases in secundary, SLE-associated antiphospholipid syndrome group. One of the patients had died because of the Catastrophic Antiphospholipid Syndrome. PMID- 11202120 TI - [Laszlo Nemeth and Albert Szent-Gyorgyi. Honoring anniversaries]. PMID- 11202121 TI - [The past, present and future of the National Medical Rehabilitation Institute]. PMID- 11202119 TI - [Raynaud syndrome and eradication of Helicobacter pylori]. AB - In this work, the effect of eradication of Helicobacter pylori on complaints and symptoms of infected, primary Raynaud's syndrome patients was studied. Altogether 92 Helicobacter pylori positive patients with gastric complaints and with primary Raynaud's syndrome received eradication therapy. In this prospective study, before and after the eradication the severity and frequency of the complaints and symptoms of the patients were recorded. The eradication was performable in 89 patients; in 75 cases the eradication was successful. In the eradicated patients frequency and duration of Raynaud attacks were improved related to those of the not eradicated group. These results might suggest a potential etiopathogenetical role of Helicobacter pylori infection in the pathogenesis of the primary Raynaud's syndrome. PMID- 11202122 TI - [Remembering Gyula Petranyi, member of the Hungarian Academy of Sciences]. PMID- 11202123 TI - Attention training in the cognitive rehabilitation of schizophrenic patients: a review of efficacy studies. AB - OBJECTIVE: To review the literature on effects of attention and cognitive training on attentional functioning in schizophrenic patients. METHOD: Relevant efficacy studies were identified by literature searches (in Medline, Current Contents, Psyclit, and Psyndex databases) and through the reference lists of key papers. RESULTS: Re-examination of findings from nine methodologically adequate studies using computer-based or non-computer-based training procedures provided inconsistent results. On 16 of 35 outcome measures significant performance improvements were observed from pre-treatment to post-treatment but on the majority of the applied measures no performance improvement could be determined. In general, treatment effect sizes but also power of tests were low. For nearly all the outcome measures for which differential training effects were reported there also exist contradictory outcome results. CONCLUSION: There is inconclusive evidence that attention training is effective in schizophrenia. Longitudinal efficacy studies are needed in which different aspects of attention are systematically exercised and assessed. PMID- 11202124 TI - Making psychiatric epidemiology useful: the contribution of epidemiology to government policy. AB - OBJECTIVE: This paper aims to discuss the contribution of epidemiology to aspects of public policy that have either a direct influence on mental health and mental disorders, or an indirect effect by influencing environmental factors which influence mental health. Both kinds of public policy will need to be considered by governments wishing to protect, promote and improve the mental health of their populations. The paper draws on information from both relatively wealthy and low income countries. METHOD: The paper defines epidemiology and mental health policy, sets out the range of government policies which may have an impact on mental health, and explores the ways in which epidemiology may contribute to mental health policy in relation to service inputs, processes and outcomes as well as to wider government policies. The paper also examines the advantages and disadvantages of different sources of data. RESULTS: There are a number of reasons to carry out large-scale surveys of psychiatric morbidity. First, effective policy should address the needs of the population, which can best be assessed by the epidemiology and the social and economic causes and consequences of psychiatric morbidity. Secondly, representative information in a defined geographic area can document the use of existing services and can estimate the extent of unmet needs and the services required meeting those needs. Thirdly, valid information on prevalence and associated risk factors of presumed causal importance allow aetiological hypotheses to be generated and tested and models developed for prevention. Finally, by repeating community surveys, it is possible to monitor the health of the population and trends. Epidemiological findings emphasize the importance of mental health policy addressing the key role of primary care, the social context and social consequences of disorder, the importance of addressing services for children, the need to reduce premature mortality from suicide and from physical illness. Epidemiological findings show that mental health and mental disorders are related to the environment both in its structural physical sense and in the sense of the social processes connected to and influenced by particular settings. Thus epidemiology can contribute to general policies on employment and unemployment, housing and homelessness, education and women's issues. CONCLUSION: Mental health policy is increasingly recognized as an essential area for countries wishing to enhance their economic, social and human capital. Epidemiological data are a basic prerequisite to informing such policies. Expert professional and epidemiological advice to ministries is essential if policy is to be rooted in the evidence for population needs, risk factors, effective treatments and services, and measurement of outcomes. It is therefore important to develop the capacity for policy work in the psychiatric profession by including public health, epidemiology and policy placements for young psychiatrists. PMID- 11202125 TI - Out-patient behaviour therapy in alcoholism: relapse rates after 6 months. AB - OBJECTIVE: In spite of the increasing interest in out-patient treatment programmes for alcoholics, there still exist only a few experimental studies on this issue. In this still ongoing study the efficacy of different behaviour therapy strategies is to be examined. METHOD: One hundred and twenty patients were assigned randomly to non-specific supportive therapy or to two forms of behavioural therapy (coping skills training and cognitive therapy). Behavioural treatment comprised 26 weekly sessions; follow-up examinations will take place every 6 months over 2 years. RESULTS: Patients undergoing behavioural therapy showed less drop-outs and significantly higher rates of abstinence compared with supportive treatment. Nevertheless, statistically significant differences between the two behavioural therapy strategies could not be established so far. CONCLUSION: Preliminary results demonstrate the feasibility and efficacy of behaviour therapy programmes in the out-patient treatment of alcoholism. Furthermore, they stress the importance of professional psychiatric and psychotherapeutic engagement in the field of addiction. PMID- 11202126 TI - Out-patient behaviour therapy in alcoholism: impact of personality disorders and cognitive impairments. AB - OBJECTIVE: We investigated whether alcoholic patients with comorbid personality disorders and those with cognitive impairments would benefit in a different way from different behaviour therapy strategies. METHOD: After detoxification, 120 alcoholics were assigned randomly to one of three out-patient treatment programmes comprising 'coping skills training', 'cognitive behaviour therapy' or unspecific supportive control therapy. Personality disorders and cognitive impairments were assessed at the beginning of the 6-month treatment period. RESULTS: The impact of concomitant personality disorders or cognitive impairments was generally only moderate and mainly independent from treatment condition. However, alcoholic patients relapsing within 6 months after detoxification showed a higher rate of personality disorders (especially antisocial and borderline) and slightly more cognitive deficits (especially in verbal memory and visuomotor functions) than abstainers even before therapy. CONCLUSION: The high amount of early relapses and drop-outs probably hindered larger differentiated treatment effects. Hypotheses will be retested in treatment completers using forthcoming follow-up data. PMID- 11202127 TI - Self-reported life satisfaction and recovery from depression in a 1-year prospective study. AB - OBJECTIVE: To study the relationship of a self-rated four-item life satisfaction scale (LS) to the self-rated 21-item Beck Depression Inventory (BDI) and the 17 item Hamilton Rating Scale for Depression (HAMD) and to study LS changes during recovery from depression. METHOD: A 1-year prospective study on 188 depressive patients receiving standard psychiatric outpatient treatment; 137 of the patients had major depression. RESULTS: LS correlated strongly with BDI and HAMD. It explained 46.6%) of the variation in BDI at baseline and 66.2% at 12 months. LS improved substantially during recovery. The main recovery occurred during the first 6 months, the change in the LS score explaining 46.5% of the change in the BDI score (P < 0.001). CONCLUSION: Life satisfaction is strongly affected in depression, but it improves concurrently with recovery from depression. LS scale may prove useful in screening for those whose subjective wellbeing deserves attention and in assessing alleviation from depression. PMID- 11202128 TI - Comparison of key worker and patient assessment of needs in schizophrenic patients living in the community: a Nordic multicentre study. AB - OBJECTIVE: The present study is part of a Nordic multicentre study investigating the life and care situation of community samples of schizophrenic patients. The specific aim of the present part of the study was to examine the agreement between patients and their key worker concerning the presence of met and unmet needs in a number of life domains, and help or support given in these domains. METHOD: The comparisons were based on 300 matched pairs of assessments of need using the Camberwell Assessment of Need interview. RESULTS: The results showed that key workers identified slightly more needs, 6.17 vs. 5.76, a significant difference. There was a moderate or better agreement on the presence of a need in 17 of 22 life domains investigated, but in only 11 life domains concerning the presence of an unmet need. Disagreement concerning whether the patient was given the right kind of help or support was even more substantial. CONCLUSION: It is concluded that key workers and patients disagree particularly concerning unmet needs and that this is potentially related to a number of factors associated with the key worker and patient. It is also concluded that further research is needed to increase the knowledge concerning the sources of this disagreement if need assessment is to become a valid basis for service planning and individual treatment planning. PMID- 11202129 TI - Quality of Life (QOL) of patients with Gilles de la Tourette's syndrome. AB - OBJECTIVE: This is the first study to investigate the Quality of Life (QOL) of patients with Gilles de la Tourette's Syndrome (GTS). METHOD: One hundred and three out-patients with GTS completed a semi-structured interview and 90 of these completed questionnaires screening for depression, anxiety and obsessive compulsive behaviour. QOL was measured with the SF-36 and the Quality of Life Assessment Schedule (QOLAS). RESULTS: Patients with GTS showed significantly worse QOL than a general population sample. They had better QOL than patients with intractable epilepsy as measured by the QOLAS, although the SF-36 showed significant differences on the subscales Role Limitation due to physical problems and Social Functioning only. Factors influencing QOL domains were employment status, tic severity, obsessive-compulsive behaviour, anxiety and depression. CONCLUSION: QOL is impaired in patients with GTS. Measurement of QOL could be used alongside conventional measurements to assess benefit of treatment. We recommend the QOLAS and SF-36 be used. PMID- 11202130 TI - Validation of psychiatric patients' statements on coercive measures. AB - OBJECTIVE: To investigate the accuracy of psychiatric patients' statements on coercive measures compared with medical file information using empirical methodology, and relating the statements to patients' psychopathology. METHOD: One hundred and forty-three in-patients were identified consecutively, and interviewed using a structured questionnaire. Psychopathology was measured using BPRS, and social functioning using GAF. Patients' statements about coercion were compared with information in the medical files. RESULTS: In general, patients stated to have been subjected to more coercion than was evident from the files. In particular, statements about forced medication, earlier involuntary commitments and present legal status showed low accordance with information in the files. Low accordance was related to the severity of psychopathology and being schizophrenic. CONCLUSION: The existence of a 'grey zone' between patients' and doctors' perception of coercion was confirmed. Knowledge of patients' psychopathology seems essential when considering medical, legal and ethical aspects of the use of coercion. PMID- 11202131 TI - Benefits from mianserin augmentation of fluoxetine in patients with major depression non-responders to fluoxetine alone. AB - OBJECTIVE: To assess, in depressed patients, the clinical benefit of mianserin augmentation of fluoxetine or the the benefit of switching treatment from fluoxetine to mianserin. METHOD: In a 6-week double-blind study we compared the therapeutic efficiency and tolerance of mianserin 60 mg/day (N = 34), mianserin 60 mg/day plus fluoxetine 20 mg/day (N = 32) and continuing fluoxetine 20 mg/day (N = 38) in patients with major depression who did not respond to previous fluoxetine treatment. RESULTS: Intent-to-treat analysis showed that at week 6 the decrease in the Hamilton Depression rating scale score was significantly (P < or = 0.03) greater in the mianserin plus fluoxetine group when compared to the fluoxetine group (effect size 0.665). Switching from fluoxetine to mianserin gave intermediate results. Mianserin augmentation of fluoxetine was well tolerated. CONCLUSION: Mianserin augmentation of fluoxetine in patients non-responders to fluoxetine 20 mg/day increases response to treatment and is well tolerated. PMID- 11202132 TI - Thrombosis associated with physical restraints. AB - OBJECTIVE: Physical restraint is controversial, but still frequently used in psychiatric units. We describe two cases of thromboembolic phenomena, one with a fatal outcome, in association with physical restraint. METHOD: The world literature on physical restraint and thrombosis was reviewed by undertaking a search of electronic databases. RESULTS: To our knowledge, we are the first to report thrombosis associated with physical restraint. CONCLUSION: Immobilization and trauma to the legs while restraining a patient are adequate explanations for the occurrence of thrombosis. Special attention should be paid to thrombosis when employing restraints in psychiatric wards. Further systematic research into physical restraints in psychiatry is clearly needed. PMID- 11202133 TI - Compulsive heroin use: comorbidity, syndrome or self-medication of lupus erythematosus? PMID- 11202134 TI - Epilepsia partialis continua: clinical and electrophysiological features of adult patients. AB - In this study we reviewed the clinical, electrophysiological and neuroimaging data of 21 patients with epilepsia partialis continua (EPC), which is a rare form of epilepsy with focal motor seizures persisting hours to years. We found infections, cerebrovascular events and tumors as the most common causes of EPC in adults. SSPE was also shown as a cause of EPC. EPC in SSPE patients was resistant to therapies and persisted more than 1 year. EPC is usually a predictor of poor outcome and 29% of patients died after EPC in this study. As prognosis is usually bad and as response to treatment is poor in patients who had EPC, early diagnosis and treatment of the underlying cause is important. Although the most common etiologies are infections, cerebrovascular events and tumors, if EPC persists several months SSPE should be kept in mind as a rare cause of EPC. MRI should be repeated in chronic cases to show dysplastic cortex, which was shown in 1 patient in this study. PMID- 11202135 TI - The continuous rhythmic mid-temporal discharge. AB - This case report is of a 15-year-old male who was sent for an EEG because of possible staring spells and a learning disability. At times written examinations in school were successfully completed and at other times the patient would write only his name. In two EEGs 1 month apart during hyperventilation, Rhythmic Mid Temporal Discharges (RMTD) were activated and appeared continuously for 84 minutes and in the second instance for 140 minutes. No maneuvers could modify the pattern and no clinical changes were reported by the patient. Discussion includes another similar case recently published and the need to test such patients in some way to see the subtle clinical changes that likely do occur. One compromise for the name of this pattern might be Rhythmic Mid-Temporal Epileptiform Activity (RMTEA), avoiding the term discharge, which implies a seizure state that has not yet been established. PMID- 11202136 TI - Lateralized EEG findings in patients with neuropsychiatric manifestations of systemic lupus erythematosus. AB - Routine and quantitative EEG were used to determine whether there is a lateralized pattern of electrophysiologic dysfunction in patients with diverse neuropsychiatric manifestations of SLE. Twenty consecutive patients with neuropsychiatric symptoms of SLE underwent 20-minute EEG recordings with an 18 channel polygraph. Ten 1-second intervals were randomly selected for each patient. Once selected, the intervals were analyzed for the presence of theta and delta slow activity. Mapping was done by four-point interpolation around the 18 acquired data points. On routine EEG, abnormalities were identified in 14/20 patients with SLE. In 12/14 patients, the abnormalities were localized to the left temporal region. Quantitative EEG analyses revealed theta and delta slow activity predominantly affecting the left hemisphere in 16/19 patients with SLE. Taken together, these findings suggest selective involvement of the left hemisphere in patients with diverse neuropsychiatric manifestations of SLE. PMID- 11202137 TI - Frontal lobe disinhibition, Rett syndrome and attention deficit hyperactivity disorder. AB - Motor cortex hyperexcitability in Rett Syndrome (RS) has been ascribed to the failure of an inhibiting system arising from the frontal lobes, a system needed in childhood and early adolescence. It is also presumed that, on a virtually dysfunctional (nonstructural) basis, motor cortex hyperexcitability in ADHD is also due to insufficient frontal lobe inhibition ("lazy frontal lobe"). A series of schematic illustrations is added for the sake of easier comprehension of the presented concept. PMID- 11202138 TI - Video-EEG monitoring in respiratory chain disorders. AB - Subclinical epileptiform activity in patients with respiratory chain disorders (RCDs) has not been previously investigated by video-EEG monitoring. The purpose of this study was to look for the type and frequency of epileptiform activity during a 24 h-video-EEG recording in RCD patients. Eleven patients with RCD, 7 women and 4 men, aged 24-72 years, underwent a clinical neurologic examination, blood tests, CT/MRI scans of the brain, routine scalp EEG and continuous video EEG monitoring over 24 consecutive hours. Ten patients had normal 24 h-video-EEG recordings. One of these patients had no CNS involvement; her resting EEGs showed diffuse background slowing. In one patient, automatic spike detection revealed 12 spikes during a 6 hour period. Resting scalp EEG in this patient showed extensive, bilaterally synchronous, pseudoperiodic polyspike-waves. In conclusion, subclinical epileptiform activity could be recorded by 24 h-video-EEG monitoring in only 1 of 11 RCD patients. The single patient with subclinical epileptiform activity presented with intermittent myoclonic jerks. PMID- 11202139 TI - A case of Zellweger syndrome with extensive MRI abnormalities and unusual EEG findings. AB - Differential diagnosis in a newborn with dysmorphic features and profound neurologic dysfunction should include the cerebro-hepato-renal syndrome of Zellweger. Its distinct clinical features, markedly elevated plasma levels of very long chain fatty acids and characteristic radiological findings support the diagnosis, which can now be confirmed by genetic markers. Quite consistent abnormalities of the neurophysiological studies in this syndrome have also been reported. We report a case with typical clinical and biochemical findings in whom distinctive brain MRI abnormalities were found. The results of neurophysiological studies with an unusual EEG pattern of continuous negative vertex sharp waves and spikes are discussed. We believe that such a pattern could be considered as a pathognomonic EEG finding, especially in cases of Zellweger syndrome with extensive brain abnormalities and may even be closely associated with cortical dysplasias. PMID- 11202140 TI - Unilateral alpha subharmonics: a case report. AB - Occipital alpha subharmonics are a normal EEG variant. Unilateral occipital slowing, however, is associated with focal dysfunction of that particular side. We report a 10-year-old girl with the incidental EEG finding of unilateral occipital slowing. MRI of her brain was completely normal and on long-term follow up she remained healthy. Based on her clinical history, normal MRI of brain, and the character of the slow posterior rhythms, we conclude that unilateral slow alpha rhythm can be a normal variant akin to alpha subharmonics. PMID- 11202141 TI - Decreased level of EEG-vigilance in acute mania as a possible predictor for a rapid effect of methylphenidate: a case study. AB - About one third of manic patients show a decreased Electroencephalographic Vigilance Level (EVL). In two patients with recurrent manias the hypothesis was tested that the EEG may be used to predict the therapeutic response to methylphenidate. Patient A (with a decreased EVL) responded rapidly to methylphenidate with a considerable reduction of symptoms and a clear increase of EVL, whereas patient B (normal EVL) did not show any change, neither clinically nor in the EEG. PMID- 11202142 TI - A new-type titanium intervertebral spacer and its insertion device used in posterior lumbar interbody fusion. AB - We have recently developed a new-type trapezoid mesh cage (TPM cage) together with an insertion device, which for use as a new titanium mesh intervertebral spacer in posterior lumbar interbody fusion (PLIF). The TPM cage has sufficient mechanical strength, a large contact area that gives good long-term stability, and preserves the initial disc height to provide good balance. The insertion device for the TPM cage is useful not only for handling the implant but also for controlling the implant insertion direction. The TPM cage and its insertion device are promising for use in PLIF. PMID- 11202143 TI - Hand motion assessment and rehabilitation system. AB - Along with the rapid development of information technology, computers play an increasingly prominent and important role. One current trend is to use computers as instruments for physical rehabilitation. In this study, we introduce a new hand motion assessment and rehabilitation system. This system assesses a user's grip strength and records the sudden changes in air pressure through a circuit and A/D adapter. A PC interface transforms and saves the data in a data record file. The data is then compiled and combined with a patient's case history and keyed into a database as reference for clinical use. The system is highly efficient, cheap and convenient to use. Doctors can use it to monitor and analyze the progress of a rehabilitation program. PMID- 11202144 TI - The effect of elastic modulus of the backing material on the fatigue notch factor and stress. AB - In cemented acetabular cup design it is acknowledged that bone resorption and fatigue fracture of cement may cause the most common problems after total hip replacement. Previous studies have optimized the shape of metal backing (MB) shell used in cemented acetabular components in order to minimize the fatigue notch factor (Kf) in cement, whilst at the same time maximizing Kf in bone at the central part of acetabulum to prevent stress shielding and subsequent bone resorption [1]. The optimal shape was found to be thin at the edges and thick at the dome. The present study describes the effect of changing the elastic modulus of the backing material on Kf and stresses as predicted by the initial shape of the backing shell of (3 mm) thick, and the optimized backing shape of non-uniform thickness in order to find the optimal material for the backing shell. It is recommended to use a backing shell material with elastic modulus equals 70 GPa (which can be readily attained using a fiber reinforced polymer composite). It is shown that such a material will decrease the fatigue notch factor and the stresses in cement at cup edges, at the same time it will increase the stresses and the fatigue notch factor in bone at the central part of acetabulum. Thereby, reducing the possibility of fatigue fracture of cement, whilst at the same time decreasing the stress shielding effect and the resulting bone resorption. The effect of lower bone resorption and lower probability of fatigue fracture of the cement will also reduce the incidence of loosening and premature revision operations. PMID- 11202145 TI - Hydroxyapatite-coated bioalloy surfaces: current status and future challenges. AB - The present review contains salient features of the most widely used methods for depositing hydroxyapatite (HA) coatings on bioalloy substrates. These methods range from the ubiquitous plasma spraying in air to the recently introduced ion beam enhanced deposition technique. Special attention is paid to the residual stress in the coating that arises from various sources and whose magnitude impacts the adhesion of the coating to the substrate and, hence, the efficacy of the coated part (see, for example, the in vivo performance of HA-coated orthopaedic and dental implants). Thus, the plethora of methods for estimating residual stresses in HA-coated systems are critically examined. The review concludes with a detailed presentation of ten areas for future research work. PMID- 11202146 TI - Effects of clove oil-phospholipid mixtures on rheology of gum tragacanth - possible application for surfactant action on mucus gel simulants. AB - The present study evaluates the effectiveness of specialised biomaterials consisting of clove oil- phospholipid mixtures as possible substitute surfactants in diseases of altered mucus viscosity by studying their effect on the viscosity of mucus gel simulants in vitro. Test surfactants consisting of phospholipid clove oil mixtures in the ratio of 1 part of oil to 9 parts of phospholipid were prepared. The phospholipids used were dipalmitoyl phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) and binary mixtures of PC: PE and PC: PG in the ratio of 2 parts of PC to 3 parts of PE or PG. The effects of the phospholipid-clove oil mixtures on the viscosity of mucus gel simulant (MGS: a polymeric gel consisting predominantly of gum tragacanth and simulating respiratory mucus), was studied by application of steady shear rates ranging from 0.512 to 51.2/s in a concentric cylinder viscometer at 37 degrees C. The change in MGS viscosity, after incubation with surfactants, was found to have a non-Newtonian character and to follow the power law model with R2 values >0.8. The addition of clove oil-phospholipid mixtures caused a decrease in the MGS viscosity when compared with the effect of the phospholipid alone at low shear rates in case of PC, PG and PCPG. The combination of PC : PG with clove oil caused ratios of change in MGS viscosity < 1 i.e., caused a decrease in the MGS viscosity. PC: PG with clove oil was capable of lowering MGS viscosity and should be further researched as possible therapies for diseases of altered mucus rheology. PMID- 11202147 TI - Initial strength of highpressed extrusion poly-L-lactide screw. AB - We developed a poly-L-lactide material strengthened by a highpressed extrusion technique. The bending strength of a rod made of that material is higher than that of the same size rods made of poly-L-lactide strengthened by drawing technique, which has been used in clinical cases. The purposes of this study were, first to clarify if the initial strength of extrusion-strengthened poly-L lactide screws is higher than that of draw-strengthened poly-L-lactide screws, and, secondly to investigate the safe torque for driving the screws in clinical usage. In accordance with AO screw design, five kinds of screws were manufactured. In a pull-out test and a twisting test using a DYRACON blocks, the strength of the highpressed extrusion-strengthened poly-L-lactide material was also higher than that of the draw-strengthened poly-L-lactide material after milling into screws. In the simulation using minipig bones and the 4.5 mm psi cortical screws, when the thickness was below 0.5 mm, between 0.5 and 2 mm or over 3 mm, the break locations were in the cortical bone, the thread of the screw and the under head fillet respectively. In the simulation using minipig bones and the 4.0 mm psi cancellous screws, breakage occurred not on the screws but on the cancellous bone in all screws. PMID- 11202148 TI - Morphology and formation mechanism of hydroxyapatite coating by hydrothermal method on CaO-SiO2-B2O3-Na2O glass. AB - Hydrothermal method was used to prepare the hydroxyapatite (HA) coating on CaO SiO2-B2O3-Na2O glass. The phase composition, morphology and microstructure of HA coated glass composites were analyzed using XRD, EPMA, FT-IR and SEM techniques. It revealed that HA coating possessed a porous gradient construction; HA coating was tightly bonded with the glass substrate by the interface layer. During the formation of HA coating, the hydrated silica produced by the corrosion of glass substrate in the hydrothermal solution provided favorable sites for apatite nucleation. With the dissolving of HA powder and the growth of apatite small crystallites, Ca+, PO(4 (3-)) ions would precipitate on the surface of glass to form the HA coating. Silicon element released from glass reacted with calcium produced by the dissolution of HA to form the tight reaction layer. HA coating is formed by the mechanism of dissolving-ions immigrating-precipitating pattern. PMID- 11202149 TI - Dissolution behavior of hydroxyapatite coating by hydrothermal method: an in vitro study. AB - Hydroxyapatite (HA) coated CaO-SiO2-B2O3-Na2O glass composites prepared by a hydrothermal coating method were soaked in four kinds of solutions to evaluate the dissolution behavior and the chemical stability. 0.5 mol/l HCl and 0.5 mol/l HNO3 were used as acidic solution, and 5% physiological saline and sodium lactate compound solution as the neutral physiological solution. It was found that HA coated glass composites had the better chemical stability and the corroding resistance ability. The dissolution behavior of the HA coating was mainly correlated with the phase composition of the as-received HA coating and its microstructure as well as the pH value of the solution. PMID- 11202150 TI - Crystal chemistry of hydroxyapatite deposited on titanium by sputtering technique. AB - Crystalline hydroxyapatite (HA) powder was coated on titanium substrate by radio frequency (RF) magnetron sputtering. The coating was homogeneous thin film and the thickness was 1microm. Crystallinity of the HA coating was low and Ca/P ratio was high as 3.0. Particle sizes were 40 to approximately 100 nm, and the crystallite size was calculated by 30 to approximately 50 nm using an X-ray diffractometry (XRD) and a transmission electron microscopy (TEM). When the coating was heated at 800 degrees C for 1 h, the low crystalline HA grew up crystalline HA, and a diffraction pattern of CaO appeared. When the coating was immersed in pH 7.4 of bovine serum for 1 week, c-axis of HA increased. PMID- 11202151 TI - Comparison of the response of primary murine peritoneal macrophages and the U937 human histiocytic cell line to challenge with in vitro generated clinically relevant UHMWPE particles. AB - The response of primary murine macrophages and the U937 human histiocytic cell line to challenge with clinically relevant UHMWPE wear debris of known particle size and dose was evaluated. Particles with mean sizes of 0.24, 0.45, 1.71, 7.62 and 88 microm were co-cultured with cells for 24 hours prior to assessment of cell viability and production of the osteolytic mediators IL-1beta, IL-6, TNFalpha and, in supernatants from murine phagocytes, PGE2 and GM-CSF. All particle fractions were evaluated at particle volume (microm3) to cell number ratios of 10 : 1 and 100 : 1 (and, additionally, 0.1 : 1 and 1 : 1 for U937 cells). These ratios had previously been identified as the most stimulatory and clinically relevant. Although the results for the cell line were highly variable, stimulation with phagocytosable particles (range 0.1 to 15 microm) resulted in enhanced levels of cytokine secretion by both murine macrophages and U937 histiocytes. The most biologically active particles were sub-micrometre in size. However, U937 cells responded to wear debris at much lower particle volume to cell number ratios (>0.1 microm3 per cell) than the murine cells (> 10 microm3 per cell). No GM-CSF was produced by particle or LPS stimulated murine macrophages. Similarly, U937 histiocytes failed to secrete any IL-1beta. Neither macrophage population responded to stimulation with the largest (88 microm) particles. These results confirm earlier findings and suggest that the size of UHMWPE wear particles is a critical factor in macrophage activation. Moreover, primary murine macrophages have been demonstrated to be a suitable model for studying cell-particle interactions in vitro. PMID- 11202152 TI - A multi-directional wear screening device and preliminary results of UHMWPE articulating against stainless steel. AB - This paper describes the design of a pin on plate rig which has been modified to give multi-directional motion to the test pins, resulting in elliptical and quasi elliptical wear paths. Such paths are closer to those seen in vivo by a femoral head articulating against an acetabular cup. The description of the rig is augmented by the results of a test of ultra high molecular weight polyethylene pins rubbing against stainless steel plates. with dilute bovine serum at 37 degrees C being used as the lubricant. With standard reciprocating motion, a mean wear factor of 0.085 x 10(-6) mm3/N m was found, but with multi-directional motion, the mean wear factor increased to 1.10 x 10(-6) mm3/N m, which is very similar to in vivo wear factors. PMID- 11202154 TI - The effect of dibutyryl cyclic AMP on the expression of actin isoforms in astroglia. AB - Mammalian cells contain at least 8 actin isoforms. The functional significance and the mechanisms that regulate the expression of each actin isoform are not yet known. Using immunofluorescence staining, it was found that all astroglia in tissue culture express beta-actin isoform and about 86% of astroglia express alpha-smooth muscle actin isoform. When astroglia were treated with dibutyryl cyclic AMP for 4, 7, 14 and 21 days, it was found that the number of the cells expressing alpha-smooth muscle actin isoform progressively decreased, whereas, the number of the cells expressing beta-actin isoform remained constant. The western blot experiment showed that the amount of total alpha-smooth muscle actin isoform (soluble and insoluble) and of the insoluble isoform expressed by astroglia treated with dibutyryl cAMP decreased whereas, the amount of total and insoluble beta-actin isoform expressed by the same cells did not show any significant changes. The cells treated with the cAMP failed to migrate and to close the area created by the scratch wound in monolayer culture. However, the non-treated cells migrated and closed the area created by the scratch after 3 days. This study shows that the astroglia have different mechanisms in regulating the expression of different actin isoforms and that the alpha-sm actin isoform is important in migration of astroglia. PMID- 11202155 TI - Immunohistochemical localization of type I collagen, fibronectin and tenascin C during embryonic osteogenesis in the dentary of mandibles and tibias in rats. AB - Type I collagen, fibronectin and tenascin C play an important role in regulating early osteoblast differentiation, but the temporal and spatial relationship of their localization during embryonic osteogenesis in vivo is notknown. The present study was designed to localize these three molecules in the dentary of mandibles and tibias in rat embryos using immunohistochemistry. Serial paraffin sections were cut and adjacent sections were processed for von Kossa staining or immunohistochemistry for type I collagen, fibronectin and tenascin C. In the dentary, tenascin C was localized within and around the mesenchymal cell condensation in embryos at 14 days in utero. The bone matrix at 15 days showed immunoreactivity for both type I collagen and fibronectin. The immunoreactivity of type I collagen was persistent, whereas that of fibronectin decreased with age of embryos. In tibias, tenascin C was localized in the perichondral mesenchymal tissue at 17 days. Immunoreactivity for type I collagen was persistent in the bone matrix, whereas the tibial bone showed little immunoreactivity for fibronectin at any embryonic age examined. The present study demonstrated characteristic localization of type I collagen, fibronectin and tenascin C during embryonic osteogenesis in the dentary of mandibles and tibias. PMID- 11202156 TI - Detection of P-glycoprotein in the nuclear envelope of multidrug resistant cells. AB - P-glycoprotein is a plasma membrane efflux pump which is responsible for multidrug resistance of many cancer cell lines. A number of studies have demonstrated the presence of P-glycoprotein molecules, besides on the plasma membrane, also in intracellular sites, such as the Golgi apparatus and the nucleus. In this study, the presence and function of P-glycoprotein in the nuclear membranes of human breast cancer cells (MCF-7 WT) and their multidrug resistant variants (MCF-7 DX) were investigated. Electron and confocal microscopy immunolabelling experiments demonstrated the presence of P-glycoprotein molecules in the nuclear membranes of MCF-7 DX cells. Moreover, the labelling pattern was strongly dependent on pH values of the incubation buffer. At physiological pH (7.2), a strong labelling was detected in the cytoplasm and the nuclear matrix in both sensitive and resistant MCF-7 cells. By raising the pH to 8.0, the P glycoprotein molecules were easily detected in the cytoplasm (transport vesicles and Golgi apparatus), plasma and nuclear membranes exclusively in MCF-7 DX cells. Furthermore, drug uptake and efflux studies, performed by flow cytometry on isolated nuclei in the presence of the P-glycoprotein inhibitor cyclosporin A, suggested the presence of a functional P-glycoprotein in the nuclear membrane, but not in the nuclear matrix, of drug resistant cells. Therefore, P-glycoprotein in the nuclear envelope seems to represent a further defense mechanism developed by resistant cells against antineoplastic agents. PMID- 11202157 TI - An immunocytochemical study of intrapancreatic ganglia, nerve fibres and neuroglandular junctions in Brockmann bodies of the tompot blenny (Blennius gattoruggine), a marine teleost. AB - The innervation of the Brockmann bodies in the teleost fish, Blennius gattoruggine, was studied using immunocytochemical techniques at both the light and electron microscopy levels. Islet innervation consisted of intrapancreatic ganglia, generally localized inside the rim of the exocrine tissue of the Brockmann bodies, in proximity to the islet, nerve fibres and nerve terminals with synaptic complexes. The intrapancreatic ganglia were of variable size, with different numbers of ganglionic cells, that appeared unipolar in section. The cell bodies showed immunoreactivity to galanin, oxytocin, peptide tyrosine tyrosine and glucagon. The extrinsic and intrinsic nerve fibres passed through the exocrine parenchyma and crossed the connectival septa and islet connectival sheath, penetrating into the islets, where they became increasingly thinner. They terminated on the endocrine cells with dilated nerve terminals. At least three types of terminals were detected, depending on the different vesicle content: peptidergic, cholinergic or adrenergic. They presented specialized synaptic structures, the neuroglandular junctions, some of which contained neurosecretory granules immunogold labelled by galanin antiserum. This new finding confirms the role of galanin as a neurotransmitter. This rich supply of innervation may be important in the regulation and integration of islet secretion. PMID- 11202158 TI - Pitfalls in the immunohistochemical localization of the cystic fibrosis transmembrane conductance regulator in paraffin embedded sweat glands. AB - Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause the hereditary disease cystic fibrosis. The most frequent mutant deltaF508 has been shown in vitro to be retained in the endoplasmic reticulum. Ex vivo studies using immunohistochemical labelling in cryofixed skin biopsies have confirmed the mislocalization of deltaF508 CFTR in sweat glands. The purpose of this study was to test CFTR antibodies in paraffin-embedded skin biopsies to take advantage of the superior tissue preservation as compared to cryofixation. A panel of 7 CFTR antibodies was applied to skin sections of healthy controls and of cystic fibrosis patients homozygous for the deltaF508 mutation. Sweat gland labelling consistent with CFTR localization and different between control and cystic fibrosis tissue was obtained with 2 antibodies. Conventional staining controls confirmed the labelling specificity. The antibodies were subsequently tested in a series of 237 sections of 16 biopsy specimens. However, the sweat gland labelling pattern proved not to be dependent on CFTR genotype. This finding was the sole indicator of non-specificity of the staining which was revealed only by the size of our random sample. Our results emphasize that CFTR immunolabelling following formalin fixation has to be interpreted with the utmost caution. PMID- 11202159 TI - Immunoreactivity of six monoclonal antibodies directed against 1,25 dihydroxyvitamin-D3 receptors in human skin. AB - Using confocal laser scanning microscopy, we tested the suitability of five monoclonal mouse antibodies (IVA7E7, IVB12G12, IVG9C11, VD2F12, and VIIID8C12) that had been raised against different domains of the porcine intestinal 1,25 dihydroxyvitamin-D3 receptor (VDR), for the immunohistological detection of VDR in human skin. The VDR immunoreactivity of these antibodies was compared with the well-characterized VDR-staining pattern of the mouse monoclonal antibody 9A7gamma raised against chick intestinal VDR. All six antibodies revealed strong nuclear and qualitatively similar immunoreactivity in all cell layers of the viable epidermis. Our data demonstrate that the five mouse monoclonal antibodies are suitable for immunohistochemical detection of VDR in frozen sections. These antibodies show comparable staining patterns in human skin even though they had been raised against different functional domains of the 1,25-dihydroxyvitamin-D3 receptor. PMID- 11202160 TI - Evolution in the treatment of complex blunt liver injuries. AB - Over the last decade, major changes in the treatment of patients with blunt liver injuries have occurred, specifically with the nonoperative treatment of more complex injuries. These major changes can be summarized as follows: 1. Patients with blunt liver injuries are screened expeditiously by surgeon-performed ultrasonography. Depending on the initial findings and response to resuscitation, further decisions are made regarding the further evaluation. 2. Computed tomographic scanning is the mainstay of diagnosis for hepatic injuries after blunt trauma; the initial CT findings will help the trauma surgeon to determine the nonoperative treatment. 3. Liver injuries of grades I through III can be observed safely in a monitored unit and not necessarily in an ICU setting. Patients with injuries of grades IV and V are best initially observed in an ICU. 4. More than two thirds of patients with injuries of grades IV and V can be treated nonoperatively. However, 50% of these patients will require some type of interventional treatment, but not necessarily a laparotomy. 5. Initial findings on the CT scan can help to identify those patients who will need some type of interventional treatment and to identify associated injuries. 6. Elderly patients or patients with associated medical comorbidities can also be treated nonoperatively if strict guidelines are followed. 7. Complications in patients with complex blunt liver injuries are not uncommon. However, most of the complications can be safely treated by less invasive procedures. PMID- 11202161 TI - [Energy metabolism of free-radical and microsomal oxidation in workers engaged into oil-processing industry]. AB - The authors present data on disorders of energy metabolism in erythrocytes, of microsomal monooxygenases and of free-radical oxidation in blood and urine of workers engaged into oil-processing industry. Studies revealed considerable changes in RBC adenyl system parameters, in chemiluminescence of blood and urine, in monooxygenase system. Nonspecific therapy in sanatorium appears to better these aspects. PMID- 11202162 TI - [Characteristics of work conditions in mullitic refractories production]. AB - Specific feature of occupational medicine in highly aluminiferous mullitic refractories production nowadays is dust factor associated with disintegration, crushing and pressing of fireclays and coal clays. Therefore average shift dust levels increase and considerably exceed the MAC. Calcination process is associated with slightly exceeded MAC for sulphur dioxide and carbon dioxide and MAL for noise. PMID- 11202163 TI - [Ethics of biomedical research in occupational medicine]. PMID- 11202164 TI - [Financial and economic principles of assessing enterprises' insurance premium for mandatory social worker's compensation]. AB - The authors analyzed present enterprises' insurance premiums, pointed out the associated drawbacks, defined main financial and economic principles underlying determination of enterprise's insurance premium (principle of sufficiency, principle of justice, principle of collective responsibility and principle of stimulation). PMID- 11202165 TI - [Approaches to occupational evaluation of allergy danger caused by work conditions]. AB - The authors defined major criteria for allergenic danger caused by work conditions. The criteria include sensibilizing activity, intensity of chemical allergen, routes of its intake, combinations and associations with other occupational hazards and, according to hygienic classification of work and to classification of chemical allergens, to importance in causing the allergic diseases, are assessed in points. Using the criteria, considering various associations of allergies and concomitant factors and their correspondence to occurrence and severity of immunologic and allergic disorders, clinical signs of allergies (including occupational), the authors specified integral scale for evaluation of allergenic danger caused by work conditions. PMID- 11202166 TI - [Occupational regulations of the use of terpene compounds in the air of the workplace]. AB - Based on results of 15-years complex study, the authors present toxicological and hygienic characteristics of terpene compounds (with mono- and bicyclic structure) and their compositions. The article deals with toxicodynamics and toxicokinetics of terpenoids, dependence of toxic properties on the chemical structure. The article also touches upon studies of biologic and specific (sensibilizing activity, embryotoxic and gonadotropic, membranotropic) effects of terpenoids. Some aspects concerning hygienic regulation of terpene compounds are also covered. PMID- 11202167 TI - [The use of computer-simulated systems for risk analysis]. PMID- 11202168 TI - [Bernardino Ramaccini]. PMID- 11202169 TI - [Psychophysiologic tests for early diagnosis of central nervous system's chronic exposure to organic solvents]. AB - The authors studied value of laboratory CNS tests in early diagnosis of chronic exposure to organic solvents. The tests include quantitative and qualitative evaluation of personal profile, higher psychic functions and bioelectric activity of brain. Findings are objective parameters of early CNS response to solvents- EEG signs characteristic for hypothalamic irritation, moderate diffuse increase in MMPI personal profile with secondary neurotic type and marked disorder of attention that is considerably influenced by nonspecific activating system of brain. PMID- 11202170 TI - Inclusion-body myositis: newest concepts of pathogenesis and relation to aging and Alzheimer disease. AB - We review the newest advances related to seeking the pathogenic mechanism(s) of sporadic inclusion-body myositis (s-IBM) and present the pathologic diagnostic criteria of s-IBM. We discuss the possible pathogenic role of several themes, such as 1) increased amyloid-beta precursor protein (AbetaPP) and of its fragment Abeta; 2) phosphorylation of tau protein; 3) oxidative stress; 4) abnormal a) signal-transduction, b) transcription, and c) RNA accumulation; 5) "junctionalization" and myogenous" denervation; and 6) lymphocytic inflammation. Evidence is provided supporting our hypothesis that overexpression of AbetaPP within the aging muscle fibers is an early upstream event causing the subsequent pathogenic cascade. The remarkable pathologic similarities between s-IBM muscle and Alzheimer disease (AD) brain are discussed, and the possible cause and significance are addressed. PMID- 11202171 TI - Amyloid deposition in diffuse plaques may or may not start at the neuronal cell surface membrane. PMID- 11202172 TI - High frequency stimulation of the subthalamic nucleus increases the extracellular contents of striatal dopamine in normal and partially dopaminergic denervated rats. AB - The subthalamic nucleus (STN) has come under focus in Parkinson disease (PD) because of recent advances in the understanding of the functional organization of the basal ganglia in normal and pathological conditions. Manipulations of the STN have been described to compensate for some imbalance in motor output of the basal ganglia in animal models of PD and have been proposed as a potential therapeutic target in humans. Indeed, high frequency stimulation (HFS) (130 Hz) of the STN has beneficial effects in severe parkinsonian patients but the precise mechanisms underlying these clinical results remain to be elucidated. To date, very little is known concerning the effect of HFS-STN on striatal dopaminergic transmission. Since it has been reported that dopaminergic medication may be reduced in PD patients under HFS-STN, our goal was to study the effect of HFS-STN on striatal dopamine (DA) transmission by using intracerebral microdialysis in normal and partially DA denervated rats. Our results show that HFS STN induces a significant increase of extracellular DA in the striatum of normal and partially DA lesioned rats while striatal extracellular levels of DOPAC were not affected. We conclude that HFS-STN acts directly and/or indirectly on striatal DA levels in control or partially DA lesioned rats. PMID- 11202173 TI - Expression pattern of CXCR3, CXCR4, and CCR3 chemokine receptors in the developing human brain. AB - Chemokine receptors are essential components of the immune and central nervous systems, but little is known about their distribution during development. We evaluated the distribution of 3 chemokine receptors: CXCR3, CXCR4, and CCR3 in the human developing brain. Of these, CXCR3 was the only receptor expressed in fetal brain at 26 wk of gestation and its expression was restricted to glial cells, endothelial cells, and the choroid plexus. Neuronal staining was only seen at term in the Purkinje cells of the cerebellum. CCR3 appeared only at term in both neurons and glial cells. The expression pattern of these 2 receptors in the late gestation and term resembled that of adults. CXCR4 could not be detected in the fetal brain on neurons nor on glial cells. By examining pediatric cases, we determined that CXCR4 expression commences sometimes between 3.5 and 4.5 yr. Two of the chemokine receptors examined, CCR3 and CXCR4, can be used as co-receptor together with CD4 for HIV entry, but neither was expressed during the second trimester of pregnancy. Our findings suggest that it is unlikely that CCR3 or CXCR4 play a major role in HIV-1 transmission in the fetal brain before 37 wk of gestation. PMID- 11202174 TI - Effects of sodium and chloride on neuronal survival after neurite transection. AB - An in vitro investigation was undertaken to study the roles of Na+ and Cl- in mammalian spinal cord (SC) neuron deterioration and death after injury involving physical disruption of the plasma membrane. Individual SC neurons in monolayer cultures were subjected to UV laser microbeam transection of a primary dendrite. Neurons lesioned in modified ionic environments (MIEs) where 50%-75% of the NaCl was replaced with sucrose had higher survival (65%-75%) than neurons lesioned in medium with normal (125 mM) NaCl (28%; p < 0.001). Subsequent experiments found a comparable increase in lesioned neuron survival in MIEs in which only Na+ was replaced with specific ionic substitutes; however, replacement of Cl- was not protective. Electron microscope examinations of neurons fixed <16 min after lesioning showed a dramatic decrease in vesiculation of the smooth endoplasmic reticulum and Golgi apparatus in the low NaCl or low Na+ MIEs. It is hypothesized that Na+ entry after membrane disruption may stimulate elevation of [Ca+2]i leading to ultrastructural disruption and death of injured neurons. The results of these studies suggest that a low NaCl MIE may be useful as an irrigant to limit damage spread and cell death within CNS tissues during surgery or after trauma. PMID- 11202175 TI - Neurons in Niemann-Pick disease type C accumulate gangliosides as well as unesterified cholesterol and undergo dendritic and axonal alterations. AB - Niemann-Pick disease type C (NPC) is a lethal neurologic storage disorder of children most often caused by a defect in the protein NPC1. To better understand the disease we thoroughly characterized the cellular and morphological alterations occurring in murine, feline, and human NPC. Using immunocytochemistry and filipin histochemistry we show that both gangliosides and unesterified cholesterol are differentially stored in neurons of the cerebral cortex, cerebellum, and hippocampus, as well as in liver. Double fluorescence labeling revealed that GM2 ganglioside and unesterified cholesterol were partially co localized in vesicular structures, and triple fluorescence labeling utilizing a LAMP-1 antibody identified many of these organelles as part of the late endosomal/lysosomal pathway. These observations, coupled with the proposed role of NPC1 in intracellular cholesterol movement, suggest that GM3 and GM2 gangliosides as well as unesterified cholesterol may be retrogradely cleared from late endosomes/lysosomes by an NPC1-dependent mechanism. Cellular consequences of the NPC metabolic defect as shown by parvalbumin immunocytochemistry and rapid Golgi staining, respectively, revealed characteristic axonal spheroids on GABAergic neurons and ectopic dendritogenesis that followed a species-specific gradient of: mouse < feline < human. These studies suggest that the homeostatic regulation of gangliosides and cholesterol in neurons is mediated by NPC1 and that perturbations in this mechanism cause a complex neuronal storage disorder. PMID- 11202176 TI - Schwann cell dependence of regenerating rat sensory neurons is inversely related to the quality of axon growth substratum. AB - It is still controversial to what extent elongation of regenerating sensory axons depends on proliferating Schwann cells (SCs) in an injured peripheral nerve. We hypothesized that such regeneration was independent of SC support early after nerve injury, but later became SC-dependent. The sural nerve in rats was crushed, and freezing destroyed cells but not their basal laminae (BL) in the distal nerve segment. Sensory axon elongation was assessed by the nerve pinch test and their abundance was examined immunohistochemically. Sensory axons regenerated fairly rapidly during the first week even if SC migration was prevented. Thereafter, they ceased to elongate and withdrew until their terminals contacted the SCs migrating from the proximal nerve segment. Intrinsic neuronal capacity for growth without cell support, however, had not been lost. Rather, progressive degradation of the former SC BL and loss of laminin in the acellular segment arrested axon growth. Further elongation occurred only when SC migration was possible, corroborating our hypothesis. Sensory neurons continued to elongate and maintain their axons in spite of deteriorating growth substratum if, prior to injury the axons had been allowed to sprout into the denervated skin. Previous sprouting exposed the sensory neurons to high levels of NGF. PMID- 11202177 TI - Distinct differences in binding capacity to saccharide epitopes in supratentorial pilocytic astrocytomas, astrocytomas, anaplastic astrocytomas, and glioblastomas. AB - We monitored the expression of glycan-binding sites on a panel of 10 biotinylated neoglycoconjugates by means of quantitative computer-assisted microscopy to further study the molecular mechanisms in the extensive infiltration of the surrounding brain parenchyma by most astrocytic tumors. Three distinct histological compartments were analyzed for each of the 108 astrocytic tumors (15 pilocytic astrocytomas (WHO grade I), 25 astrocytomas (WHO grade II), 30 anaplastic astrocytomas (WHO grade III), and 38 glioblastomas (WHO grade IV) included in our series. These compartments were tumors (nonperivascular tumor astrocytes), perivascular tumor astrocytes, and blood vessel walls. Clear differences were observed between the pilocytic and the diffuse astrocytic tumors. Furthermore, malignant progression in the latter category was paralleled by a decrease in cells' ability to bind distinct sugar epitopes, especially the D GalNAc(alpha1-3)-D-GalNAc-beta1-R determinant of the Forssman pentasaccharide in tumors, the alpha-L-fucose in perivascular tumor areas, and the beta-D-glucose in tumor vessel walls. Markedly, the level of binding site expression for alpha-D mannose decreased in the tumors, the perivascular tumor areas, and the vessel walls. These glycohistochemical results imply the functional relevance of protein carbohydrate interactions in this tumor system. PMID- 11202178 TI - Matrix metalloproteinase expression and inhibition after sciatic nerve axotomy. AB - Wallerian degeneration is characterized by breakdown of myelin and axons with subsequent macrophage infiltration and removal of the degenerating nerve components. Proteinases of the matrix metalloproteinase (MMP) family seem to play an important role in demyelinating processes, since some of their members have been shown to cleave myelin basic protein. In the present study we investigated the expression of MMP-2 and MMP-9 (gelatinases A and B) during myelin removal after peripheral nerve trauma. After transection of the sciatic nerve an upregulation of MMP-2 and MMP-9 with a first peak 12 h and a second peak 48 h after axotomy was observed by zymography. These peaks correlate with the breakdown of the blood-nerve barrier, the accumulation of granulocytes, and the invasion of macrophages into the damaged nerves, respectively. Furthermore, MMP-2 was found to be upregulated in the contralateral nontransected nerves. Immunocytochemistry for MMP-9 and in situ zymography identified MMP-reactive cells within the distal nerve stump. Chloracetate esterase staining was used to detect granulocytes, which accumulated at the transection site and were colocalized with the in situ zymography signal. Wallerian degeneration of the transected nerve could be delayed either by intraperitoneal injections of hydroxamate (Ro 31-9790), a nonspecific MMP inhibitor, or by local application of an MMP-9-specific antibody. Following these treatment strategies, a decreased number of invading macrophages was seen in the nerves associated with an increased amount of preserved myelin sheaths. These results suggest that the invasion of macrophages into a transected peripheral nerve is accompanied by an increased expression of MMPs, particularly MMP-9. Thus, MMPs may seem to play an important role in the breakdown of the blood-nerve barrier and subsequent cell recruitment from the systemic circulation into the damaged nerve. PMID- 11202180 TI - [Adaptive reactions of the cell as the staring point of tumor progression]. PMID- 11202179 TI - Codeposition of cystatin C with amyloid-beta protein in the brain of Alzheimer disease patients. AB - Immunohistochemical analysis of brains of patients with Alzheimer disease (AD) revealed that the cysteine proteinase inhibitor cystatin C colocalizes with amyloid beta-protein (Abeta) in parenchymal and vascular amyloid deposits. No evidence of cerebral hemorrhage was observed in any of the brains studied. Immunoelectron microscopy demonstrated dual staining of amyloid fibrils with anti Abeta and anti-cystatin C antibodies. Cystatin C immunoreactivity was also observed in amyloid deposits in the brain of transgenic mice overexpressing human beta amyloid precursor protein. Massive deposition of the variant cystatin C in the cerebral vessels of patients with the Icelandic form of hereditary cerebral hemorrhage with amyloidosis is thought to be responsible for the pathological processes leading to stroke. Anti-cystatin C antibodies strongly labeled pyramidal neurons within cortical layers most prone to amyloid deposition in the brains of AD patients. Immunohistochemistry with antibodies against the carboxyl terminus of Abeta(x-42) showed intracellular immunoreactivity in the same neuronal subpopulation. It remains to be established whether the association of cystatin C to Abeta plays a primary role in amyloidogenesis of AD or is a late event in which the protein is bound to the previously formed Abeta amyloid fibrils. PMID- 11202181 TI - [Separation from umbilical cord blood and clinical use of hematopoietic stem cells]. PMID- 11202182 TI - [Arterial chemoinfusion for treatment of unresectable malignant tumors of the liver]. PMID- 11202183 TI - [The tumor-associated antigen CA-125 under normal and in pathologic conditions]. PMID- 11202184 TI - [Mortality from malignant neoplasms in the vital statistics of Saint-Petersburg]. PMID- 11202185 TI - [Polymorphism of the GSMT1 gene in lung cancer resistance and susceptibility]. AB - The published studies of onco-associated genetic polymorphisms are characterized by insufficient interlaboratory reproducibility. The inconsistency of the results can be partially attributed to some characteristics of patients and control groups, which are used for the comparison of allele frequencies. For instance, many investigations involve so-called "healthy donors" as a standard. However, the efficiency of such a comparison can be questioned; indeed, as an individual life-time risk of malignancy reaches as high as 40-50%, a significant part of "healthy donors" would soon or later become the oncological patients. Here we tested the advantage of using "true" oncologically tolerant individuals as an additional control, e.g. tumor-free people, who succeeded to achieve an elderly age without signs of any neoplastic disease. GSTM1 gene polymorphism was used as a "positive control" for this novel design of molecular epidemiological study, as the GSTM1-null genotype displays slight but reproducible association with lung cancer risk. In the present investigation, GSTM1-deficiency was detected in 45% elderly tumor-free individuals, 55% healthy middle-aged donors, and 59% lung cancer patients. The minimal frequency (43%) of GSTM1(-) genotype was detected in elderly tumor-free smokers, and the maximal one (100%) was found in never-smoking lung cancer patients. Thus, the comparison of lung cancer patients to the "true" oncologically tolerant cohort (elderly tumor-free individuals, especially smokers) revealed more demonstrative deviations for the unfavorable genotype, than the traditional comparative analysis between oncological patients and healthy donors. PMID- 11202186 TI - [Multifactorial analysis of risk factors for lung cancer in the city of Tula]. AB - A multifactorial epidemiologic study of high incidence of lung cancer was conducted in the city of Tula. Mathematical methods of pattern recognition were used. The influence of 20 factors of risk was evaluated. The leading ones were tobacco smoking, occupational exposure to carcinogenic substances and precancerous lesions in the lungs. The influence of industrial pollution on cancer morbidity was assessed as moderate. Mathematical estimates for effectiveness of correction of "controllable" risk factors were given. PMID- 11202187 TI - [Arterial chemoembolization for metastatic colorectal cancer in the liver]. AB - Transcatheter hepatic artery chemoembolization (THACE) for inoperable colorectal carcinoma metastatic to the liver has been evaluated. Cytostatics were given to 67 patients (Dioxadet 10-30 mg--23; Doxorubicin 40-100 mg--44) in 183 courses using oil and gelatin sponge (1986-1999). Response to treatment (partial decrease in tumor size or growth stabilization) for Dioxadet and Doxorubicin was 47 and 66%, respectively; major complications--17% (fatalities--9%) and 11%, respectively. Mean survival rate was 10 and 11 months; median survival--9 and 10 months, respectively. Repeated THACE-assisted treatment with Doxorubicin was followed by mean survival of 14 months, median--12; one-year survival increased by 77%. THACE-mediated treatment with Dioxadet proved less effective and involved more complications. Further research in modifications of endovascular intervention is needed, including their combinations with systemic treatment of metastatic cancer of the liver. PMID- 11202188 TI - [Intraepithelial mononuclear lymphocytes and progression of stomach and colon cancers]. AB - Levels of intraepithelial lymphocytes were assayed in 60 bioptic samples taken from the stomach and colon. The pathologies included non-specific inflammation, benign epithelial proliferation, adenoma with grave epithelial dysplasia and adenocarcinoma. Among the methods used were routine histological staining, direct immunostaining with FITC-conjugated monoclonal antibodies against the human antigen CD4 and antibody Fab-fragment as well as an original procedure for DNA identification. In the colon, adenocarcinoma was distinquishable a high level of intraepithelial CD4(+) lymphocytes while, in the stomach, this was true for tubular adenoma with grave epithelial dysplasia, too. PMID- 11202189 TI - [Effect of gestagen therapy on clinical and biochemical parameters in patients with atypical endometrial hyperplasia]. AB - The investigation involved 22 reproductive and menopausal women (aged 30-48) with atypical endometrial hyperplasia. In addition to general clinical examination, all the patients underwent ultrasound scanning of the organs of the small pelvis, hysteroscopy and diagnostic curettage for morphological examination both before and after treatment. All tissue samples taken before and after treatment were assayed for cytoplasmic and plasma-membrane receptor levels and a number of biochemical parameters of plasma membranes. Hormone therapy with prolonged release gestagen-based drugs pointed to changes which occurred in: (1) sex steroid reception at cytosol and plasma-membrane levels; (2) the lipids profile of plasma membranes, and (3) activity of membrane-related enzymes. Among the beneficial results of gestagen treatment was coming most of lipid profile parameters and plasma-membrane enzymes back to normal. However, a decrease in the progesterone reception level in target tissue after 3-6 month treatment may suggest a likelihood of development of tolerance to gestagen. The data also suggest that further research continue in this area of endometrial precancer. PMID- 11202191 TI - [Apoptosis and proliferation of epithelial cells in papillomaviral and chlamydial cervicitis]. AB - Patients with chlamydial and papillomaviral cervicitis show a significantly higher activity of the ectocervical epithelium which is particularly pronounced in papillomaviral infection. This is, however, matched by progressively reduced apoptosis of epithelial cells which in turn suggests the possibility of papillomaviruses and chlamydiae contributing to inhibition of infected cells and, thus, paving the way for development of precancer and cancer of cervix uteri. PMID- 11202190 TI - [Diagnostic and prognostic significance of some laboratory indices of cerebrospinal fluid in multiple myeloma]. AB - beta 2-microglobulin (beta 2-m) and certain other characteristics of liquor have been followed in the course of multiple myeloma (MM) versus severity of the disease and its response to chemotherapy, to establish the diagnostic and prognostic value of these indices. Lymphocytes and plasma cells were found in most of 17 patients under study, who were resistant to chemotherapy and relapsed; they revealed regular rise in liquor pressure and cytosis. Similarly, raised concentrations of beta 2-m were registered. However, there was no correlation between blood serum-beta 2-m levels and that in cerebrospinal fluid (CSF) nor between CSF-beta 2-m concentration, on the one hand, and such parameters as CSF total protein, blood serum-beta 2-m and pathologic cytosis, on the other. In advanced MM, CSF-beta 2-m levels were, as a rule, abnormally higher. Our data suggest that, in addition to assaying CSF-total protein, severity of cytosis and liquor pressure as well as morphological identification of detected cells, beta 2 m levels be followed in the course of the disease in MM patients, to make therapeutic correction possible. Moreover, CSF-beta 2-m level dynamics can be used as another factor of prognosis. PMID- 11202192 TI - [Chemobiokinetics of sarcolysin and its peptides with glutaminic acid]. AB - A 14C study of chemobiokinetics of sarcolysin and its peptides of glutaminic acid, dosage and routes of administration was conducted in intact rats and those bearing Walker's carcinoma. Similar in shape for peptides, kinetic curves differed from those found for sarcolysin. The rates of absorption and excretion of sarcolysin peptides in intraperitoneal and, particularly, oral administration were lower than those of sarcolysin. Tumor appeared to play a role in a higher rate of peptide excretion. While sarcolysin and its peptides distribution in organs and tissues was generally identical, time of peak radioactive concentration build-up was different. Time needed for accumulation and excretion of peptides from tumor was much longer than from other organs or tissues. Sarcolysin went chiefly to urine while peptides--to faeces. PMID- 11202194 TI - [Specific response to benzo(a)pyrene treatment depending on mode of administration in rats]. AB - Mathematical and statistical procedures were used to identify individual response in rats to benzo(a)pyrene (BP) treatment versus dose and regimen (single or repeated administration). Primary experimental data were suitably processed to exclude extreme values. A significant correlation was established between life span and urine level of (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene (7,8 BP) after BP administration. It was found that, with single administration regimen, individual response to the carcinogenic agent correlated primarily with efficiency of excretion of the active forms of BP while in chronic experiment- with deactivation of the agent by enzymes. PMID- 11202193 TI - [Cyclophosphamide-induced apoptosis of murine lymphosarcoma cells in vivo]. AB - The antitumor action of combination chemotherapy (cyclophosphamide + adriamycin + vincristin + prednisolone) for transplantable nitrosomethylurea-induced lymphosarcoma was studied in male CBA mice. Single injections of the mixture were followed by complete regression of tumors of up to 2 cm in diameter. The effect was shown to be caused by cyclophosphamide (CP) alone, by inducing apoptosis. The other components failed to potentiate the CD effect. Being useless, they are likely to cause harm by contributing to the overall toxic effect of therapy. The nature and duration of CP-induced remission appeared dose-dependent: on day 50 of the administration of 50, 100 and 150 mg/kg body, tumors were detected in 100, 55 and 0% of the animals, respectively. Such means of apoptosis induction as glycocorticoid treatment and ionizing radiation did not cause complete regression. PMID- 11202195 TI - [Treatment with Miltex for metastatic skin lesions in breast cancer] . AB - Miltex (miltefosine) is a new antiproliferation drug comprising phospholipid ingredients. It is used for topical treatment of metastatic skin lesions in breast cancer. Clinical trials of the drug were conducted in 11 breast cancer patients resistant to standard therapy. Apparent therapeutic effect (partial regression) was registered in 27.3% (3/11). Moderate toxic effects were generally confined to skin itching (36.4%) and scaling (18.2%), erythema (18.2%), and paper skin (45.5%). PMID- 11202196 TI - [Combination chemotherapy with hexamethylamine (Hexalen, Altretamine, Hexastat) and sarcolysine in advanced ovarian carcinoma]. AB - Combination chemotherapy with hexamethylmelamine (hexalen, altretamine, hexastat), 100 mg, thrice a day, per os, 14 days (out of a 28-day course) and sarcolysin, 15 mg, per os, during the first 5 days of the course, was received by 24 patients with primary advanced tumors of the ovaries, prior to or after cytoreductive surgery. Total apparent response to chemotherapy among 19 patients of the study group was 47.2%, clinically significant (plus stabilization)--94.5%, without significant untoward side-effects (vomiting--19%; leukopenia degree II III--33% and thrombocytopenia--19%). The drug proved an active component of combination therapy for advanced ovarian carcinoma. PMID- 11202197 TI - [Experience with chemotherapy for advanced pancreatic carcinoma]. AB - The effectiveness of different regimens of chemotherapy for advanced pancreatic cancer was compared in 74 cases (1995-1999). 5-fluorouracil (5FU), adriamycin and mitomycin C (FAM) were given to 12 patients, 5FU alone--23, 5FU plus leukovorin- 29, and gemcitabine alone--10. Metastases to the liver were detected in 42 (57%) patients. Partial response (40) was registered in: FAM--1 (8%); 5FU--1 (4%); 5FU + leukovorin--3 (10%); gemcitabine--3 (30%). Mean duration (40) was 5.4; 4; 6.1 and 9 months, respectively. Stabilization was recorded in 17 (23%), mean duration -4.4 months; tumor progression--49 (66%). Toxic side-effects of all the regimens were insignificant. Mean survival rates following FAM, 5FU, 5FU + leukovorin were 4.4; 4.2 and 5.6 months, respectively, while that for gemcitabine varied 3-24 months (on average--7.9 months). Survival in patients responsive to chemotherapy was 9.8; remaining patients--4.7 (p (0.05). Chemotherapy for advanced pancreatic carcinoma is a measure of palliation; its use was followed by a 20% increase in survival. Gemcitabine treatment appeared most effective. PMID- 11202198 TI - [Plasmapheresis in radiotherapy for pancreatic cancer]. AB - Although radiotherapy is known to improve the results of treatment for pancreatic carcinoma, its application is limited due to such side effects and complications as anemia, leuko-, thrombocytopenia and dyspeptic disorders. It was suggested that since these complications are primarily caused by radiotherapy itself and mass death of tumor cells, plasmapheresis might raise tolerance to radiation. This was confirmed by our experience with its use during radiotherapy course in 22 patients with pancreatic cancer. PMID- 11202199 TI - [Radiologic diagnosis of outside-of-organs neck neoplasms]. AB - To evaluate the efficiency of ultrasound (US) and computed tomography (CT) in diagnosis of neck neoplasms, 36 patients with 26 benign and 8 malignant tumors were examined. Also, 32 US-guided fine needle aspiration biopsies (FNAB) were performed. Both US and CT showed high efficiency in detecting neck masses but not in different diagnosis, except for lymphomas. However, FNAB discriminated between benign and malignant tumors with a sensitivity of 75%, specificity--96% and accuracy--90.9%. PMID- 11202200 TI - [Role of high-dose BEAM-chemotherapy and autologous hemopoietic stem cell transplantation in the treatment of drug-resistant Hodgkin disease]. AB - In 1995-1999, 67 patients with relapsed Hodgkin's disease or refractory to chemotherapy (group A--first relapse, B--primary refractory disease, and C- repeated relapse) received cytoreductive (dexaBEAM, DHAP) therapy followed by high-dose BEAM chemotherapy and autologous bone marrow or blood cell transplantation. Early postoperative transplant-related mortality rate was 4.5%. At day 100, complete remission rates were: group A--95.6%; B--74.1%; and C- 76.5%. Survival for all patients was: overall--61.9%; event-free--43.9%; disease free--46%; and relapse-free survival--49.5%. Such factors as primary refractory disease, age over 30 years and response to cytoreductive therapy had significant influence on overall survival prognosis. PMID- 11202201 TI - [A rare case of multifocal cancer of the external epithelium and mucinous glands of the larynx]. PMID- 11202202 TI - [Breast self-examination as a method of screening for breast cancer]. PMID- 11202203 TI - [The life and work of Prof. S.A. Kholdin (25th anniversary of his death)]. PMID- 11202204 TI - What happens when growth hormone is discontinued at completion of growth? Metabolic aspects. AB - Continuing growth hormone (GH) replacement therapy in patients with childhood onset GH deficiency (GHD) that persists into adulthood is an emerging issue. The prospective, long-term metabolic consequences of discontinuing GH therapy in adolescent patients with childhood-onset GHD and short stature have only recently been reported. These studies demonstrate that serum concentrations of total cholesterol, low-density lipoprotein-cholesterol and apolipoprotein B are higher in adolescents in whom severe GHD continues into adulthood. Upon discontinuation of GH therapy, serum concentrations of high-density lipoprotein-cholesterol have been found to decrease in patients with severe GHD and increase in patients regarded as GH sufficient when retested for GHD. Furthermore, total body fat and truncal fat mass increase after discontinuation of GH in both these patient groups, but more markedly in the patients with severe GHD. In adolescents with severe GHD persisting into adulthood, the discontinuation of GH therapy produces, over a period of 2 years, the accumulation of important cardiovascular risk factors that are associated with GHD in adults. Continuing replacement therapy into adulthood should therefore be considered. PMID- 11202206 TI - A lifetime of growth hormone deficiency: a US pediatric perspective. AB - At a dose of approximately 0.3 mg/kg/week, treatment with growth hormone (GH) in GH-deficient children achieves adult heights that are in close proximity to a final height SDS of -0.7 +/- 1.3 for males and -0.7 +/- 1.1 for females. Early diagnosis, treatment with adequate doses of GH and attention to compliance with therapy have contributed to these striking improvements in height gain in both males and females. Final heights of 171.6 +/- 8.2 cm in males and 158.5 +/- 7.1 cm in females have been reported. There remains a considerable educational need with regard to the transition of patients with childhood-onset GH deficiency from childhood to adulthood. Re-testing of GH secretory status is but one of the issues; others include appropriate dosing and appropriate endocrinological management. Awareness of the consequences of adult GH deficiency must be increased further among endocrinologists, patients and insurers. PMID- 11202207 TI - Optimal strategy for management of pituitary disease in the growth hormone deficient teenager. AB - The optimal treatment of chronic conditions spanning pediatric and adult clinical practice requires the establishment of clear and robust systems for managing the important period of transition of care. This principle is particularly relevant to the treatment of ongoing pituitary dysfunction after the achievement of final height and, in addition to the vital component of maintaining the confidence of the patient, encompasses a number of considerations that are particularly relevant to long-term health as an adult. These considerations include the achievement of peak bone mass, optimization of gonadal steroid and glucocorticoid replacement, and determination of the need for continuing growth hormone replacement. It is therefore necessary to consider these issues not only from the standpoint of therapeutic principles but also in the context of practical arrangements for managing the process of transition of care. Successful transition can be achieved using a variety of models, and there is clearly no single preferable option. The most important ingredient in this process is awareness of the situation by both pediatric and adult endocrinologists as well as the development of an agreed strategy within each clinical center. PMID- 11202205 TI - Growth and hormone deficiency and peak bone mass. AB - In order to define the relationship between growth hormone (GH) and peak bone mass, and the importance of the role played by GH in reaching optimal peak bone mass, several questions, discussed in this article, have first to be answered. Although the answers to some of these questions are already becoming apparent, some await the findings of further research. It is doubtful whether the results of these studies, which by definition should be long-term because of the long lag between the end of linear growth and the attainment of peak bone mass, will soon be available. In the absence of evidence-based medicine one can, however, conclude that long-term GH replacement therapy for GH deficiency in adults has no deleterious effects on bone. Indeed, despite an increase in bone turnover and an increase in remodeling space, bone mineral density and bone mineral content have been shown to increase slowly over time and to the same degree in both controlled and uncontrolled studies. PMID- 11202208 TI - Ethical dilemmas in pediatric endocrinology: growth hormone for short normal children. AB - Ethical questions surrounding the administration of synthetic growth hormone (GH) to short normal children can be grouped into the following four categories: 1) appropriateness of medical treatment when no disease or biological deficiency is present; 2) how to proceed in the face of ambiguity or uncertainty of research results; 3) difficulty in weighing the risks and benefits of treatment; and 4) who should decide? This article seeks to determine whether GH administration to normal short children is properly considered an 'enhancement', and, if so, whether such treatment would be ethically wrong. PMID- 11202209 TI - Evidence-based approach to growth hormone replacement therapy in adults, with special emphasis on body composition. AB - In the past decade, a large number of controlled clinical trials have reported positive effects of growth hormone (GH) replacement therapy in GH-deficient adults. The majority of these studies have been carried out in accordance with the guidelines for Good Clinical Practice. The data thus accumulated offer a solid baseline for practicing evidence-based medicine within this area of endocrinology. PMID- 11202210 TI - Evidence-based growth hormone therapy prediction models. AB - Prediction models describing the response of various pathophysiological states to intervention can be of value in confirming a diagnosis, determining the prognosis and promoting compliance with treatment. The rigorous evaluation process of evidence-based medicine, used to assess any diagnostic test or therapeutic intervention, should be applied to studies reporting the development, validation and application of these prediction models. The models can provide only an estimate of the average effect to be expected, so the failure of an individual to exhibit an 'average' response does not necessarily imply a problem with that patient. Further development of the models is required to overcome inherent statistical problems and to allow greater applicability to the individual patient. PMID- 11202211 TI - New paradigms for growth hormone treatment in the 21st century: prediction models. AB - Inconsistent and sometimes disappointing final height outcomes in studies in which exogenous growth hormone (GH) was given to children with short stature resulting from various causes have led to attempts to determine the factors that influence responsiveness to GH. Many such factors have been identified, including the genetically determined height potential of the child, the height deficit, current and perinatal auxological and biological factors, and, importantly, GH treatment modalities. These factors vary depending on the cause of the growth failure and during the course of childhood and treatment with GH. Data from well defined large cohorts can be entered into multiple regression analyses to derive algorithms describing the variation in growth response during a defined period and the influence on this of various factors. Pharmacoepidemiologic surveys have been particularly useful in this regard. Algorithms with low-error SD values, which have included the dose of GH as a variable, can be used to predict the response to a putative GH dose in a similar cohort or in an individual over an equivalent period. A sequential series of such algorithms can be integrated to form a predictive model. Such a model can be used for planning a course of treatment, but the patient data required for entry into the model should be easily obtainable if the model is to have widespread utility. The development of such models will allow GH treatment to be better individualized and optimized for growth and cost outcomes. Growth prediction models will facilitate realistic expectations and will permit stepwise goals to be set and monitored. PMID- 11202212 TI - Role of insulin-like growth factor monitoring in optimizing growth hormone therapy. AB - Much has been learned over the past two decades regarding the management of growth hormone (GH) deficiency in children and adolescents. Current GH therapy under ideal circumstances enables children to attain a final height within the normal range and close to their target height. However, such a successful outcome is not always achieved and the necessity to individualize treatment according to the specific needs of each GH-deficient child is now well recognized. Consensus does not currently exist as to how to formulate individualized treatment plans. Nonetheless, a clear role for a biochemical, as well as an auxological, monitoring approach has been established. Accurate determinations of height velocity and interval height increase (expressed as the change in height Z-score) continue to be the most important parameters in monitoring the response to treatment. The importance of routinely monitoring serum levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 is an emerging paradigm. Firm roles have been established for this approach in the assurance of compliance and safety (particularly to avoid long-term theoretical risks). IGF monitoring also has important potential utility as a tool to assess and optimize the response to GH therapy through dose adjustments. In years to come, we expect the development of multiple GH treatment optimization strategies, including approaches such as prediction modeling, as well as serum IGF monitoring and dose adjustments, to evolve and improve. PMID- 11202213 TI - Knockout mice challenge our concepts of glucose homeostasis and the pathogenesis of diabetes mellitus. AB - The failure of insulin to stimulate muscle glucose uptake and suppress hepatic glucose production represents two of the fundamental pathophysiologic lesions in type 2 diabetes mellitus (DM). Defining insulin action at the molecular level, therefore, provides the critical background against which to elucidate the mechanisms of insulin resistance that underlie type 2 DM, obesity and many other disorders. Over the past two decades substantial progress has been made in identifying many of the molecular mechanisms involved in insulin signaling. Much of this progress has been due to the use of homologous recombinant gene targeting. The present review examines the various insights that have been provided by studies of knockout mice strains. Taken together, the results present the possibility of a unifying hypothesis for type 2 DM, in which insulin resistance in the beta-cell synergizes with insulin resistance in the periphery to produce the two classic defects of this disease: relative hypoinsulinemia and peripheral insulin resistance. PMID- 11202214 TI - Type 2 diabetes mellitus in children: pathophysiology and risk factors. AB - Type 2 diabetes mellitus (DM) has been considered rare in the pediatric population. However, over the last decade, there has been a disturbing upswing in the rate of diagnosis of type 2 DM in the pediatric age group, mirroring the increasing rates of obesity in childhood. The pathophysiology of type 2 DM discussed in this article focuses on the delicate balance between insulin sensitivity and insulin secretion. The risk factors for youth-onset type 2 DM are presented, with careful evaluation of their impact on insulin sensitivity versus insulin secretion. PMID- 11202215 TI - Emergence of type 2 diabetes mellitus in children: epidemiological evidence. AB - There have been numerous recent reports of case series of type 2 diabetes mellitus (DM) in American Indian, African-American, Hispanic, Asian-American and white children from North America. A similar phenomenon has also been described in several other countries. Prevalence and incidence estimates vary depending on the age and ethnicity of the population, but it is estimated that type 2 DM represents 8-45% of patients with DM currently diagnosed in large US pediatric centers; however, this is likely to be an underestimation and incidence is probably rising. The young patients diagnosed with type 2 DM in the USA were generally overweight, had a strong family history of type 2 DM and often had signs of insulin resistance. The majority belonged to ethnic groups at high risk for type 2 DM. More girls than boys were diagnosed. The few data on follow-up available suggest a high prevalence of microvascular and macrovascular complications among young adults who developed type 2 DM during childhood. Type 2 DM in children has recently been recognized as a potential public health problem in North America. As obesity is currently on the increase in several industrialized or industrializing countries, a similar increase in type 2 DM in children may soon emerge worldwide, and this will require preventative measures. PMID- 11202216 TI - Treatment of type 2 diabetes mellitus in children and adolescents. AB - The treatment of type 2 diabetes mellitus (DM) is directed at decreasing insulin resistance and increasing insulin secretion. alpha-Glucosidase inhibitors slow carbohydrate absorption, resulting in reduced postprandial hyperglycemia; thiazolidinediones increase insulin sensitivity, especially in muscle and adipocytes; metformin decreases hepatic gluconeogenesis; sulfonylureas result in prolonged increases in insulin secretion; and meglitinide causes rapid, short lived increases in insulin secretion. A survey of 130 pediatric endocrinology practices in the USA and Canada indicated that 48% of children with type 2 DM were treated with insulin and 44% with one or more oral hypoglycemic agents (OHA). Of those treated with OHA, 71% received metformin, 46% sulfonylureas, 9% thiazolidinediones and 4% meglitinide. Similarly, in the three university-based diabetes centers in Florida, 50% of the children with type 2 DM were treated with OHA. Treatment is based on symptoms at presentation. Patients identified on routine testing are often treated with exercise and diet alone. Those who are mildly symptomatic at onset are often started on OHA. Patients with substantial ketosis, ketoacidosis or markedly elevated blood glucose levels are initially treated with insulin, followed by a tapering of the dose and the addition of an OHA after blood glucose control is established and symptoms subside. There are no studies of the efficacy or compliance with treatment for type 2 DM in adolescents. Treatment is currently based on the clinical experience with adults. Controlled clinical trials in children are essential. PMID- 11202217 TI - Diagnosis of maturity-onset diabetes of the young in the pediatric diabetes clinic. AB - The diagnosis of pediatric diabetes mellitus (DM) traditionally is not considered a diagnostic specialty. However, considerable heterogeneity in the etiology of DM is seen among children and adolescents, making the recognition of discrete subgroups of DM very important for determining prognosis and appropriate treatment. The subgroups that result in non-insulin-dependent DM in children are as follows: the 'honeymoon' phase of type 1 DM, type 2 DM, genetic syndromes accompanied by DM, and maturity-onset diabetes of the young (MODY). The relative prevalence of these different subgroups depends on the population being studied. In the UK, in pediatric clinics where most patients are Caucasian, MODY is over 10 times more prevalent than type 2 DM. However, type 2 DM would predominate in a clinic where most children are from populations with a high prevalence of this condition (e.g. Asian Indians). It should be emphasized that MODY comprises two discrete clinical syndromes: glucokinase diabetes and transcription factor diabetes, the latter of which results from mutations in the genes encoding hepatocyte nuclear factor (HNF)-1alpha, HNF-1beta, HNF-4alpha and insulin promoter factor-1. PMID- 11202218 TI - Thrifty genotypes and phenotypes in the pathogenesis of type 2 diabetes mellitus. AB - Dramatically high rates of type 2 diabetes mellitus (DM) have been observed in historically undernourished, recently urbanized populations. A comparable model is the high risk of DM in individuals who were growth restrained in utero and subsequently catch up in size. While it is proposed that undernutrition may somehow adversely program metabolism, both models could also be explained by genotypes that promoted survival during earlier nutritional adversity but later add to the risk of DM. Our recent studies in a contemporary birth cohort have identified two different candidate thrifty genotypes. The insulin gene VNTR III/III genotype promotes fetal growth and historically could thereby have enhanced survival during infancy. In contrast, the maternally inherited 16189 mitochondrial DNA variant is associated with restrained fetal growth and may therefore enhance the likelihood of maternal survival. Both genotypes are associated with an increased risk of adult type 2 DM in historical cohorts. However, the development of DM in individuals from contemporary birth cohorts may prove to be influenced more by genetic and other early determinants of childhood obesity. PMID- 11202219 TI - Estradiol: a protective factor in the adult brain. AB - Clinical studies suggest that estradiol acts as a protective factor in the adult brain. Postmenopausal women suffer from an increased risk of brain injury associated with neurodegenerative diseases such as Alzheimer's disease, and estrogen replacement therapy appears to decrease the risk and severity of this neurodegenerative condition. Studies using animal models show that estradiol exerts similar effects in rodents and can enhance cell survival. Therefore, we designed experiments to determine whether estradiol treatment can decrease brain injury induced by an experimental model of ischemia. Our experiments used a permanent middle cerebral artery occlusion model and physiological levels of estradiol replacement therapy. The results demonstrate that estradiol exerts profound protective effects against ischemic brain injury induced by cerebral artery occlusion and that this protective action correlates with changes in the level of gene expression of estradiol receptors and members of the Bcl-2 family. These data suggest that estrogen replacement therapy may provide important protection against age- and disease-related degenerative processes in the brain. PMID- 11202221 TI - Estrogen, bone, growth and sex: a sea change in conventional wisdom. AB - The discovery of a man with a homozygous mutation in the estrogen receptor alpha gene, which results in estrogen-receptor alpha resistance, and of males and females with autosomal recessive mutations in the CYP19 gene encoding aromatase, which leads to a failure to synthesize estrogens, has challenged conventional wisdom about the 'unimportant' role of estrogen in the male. For example, in the male, estrogen (not androgen) derived from direct testicular secretion (approximately 20%) and from extragonadal aromatization of testosterone and androstenedione (approximately 80%), is the critical sex hormone in the pubertal growth spurt, skeletal maturation, accrual of peak bone mass, and the maintenance of bone mass in the adult. Estrogen stimulates chondrogenesis in the epiphyseal growth plate increasing pubertal linear growth. At puberty, estrogen promotes skeletal maturation and the gradual, progressive closure of the epiphyseal growth plate, possibly as a consequence of both estrogen-induced vascular and osteoblastic invasion and the termination of chondrogenesis. In addition, during puberty and into the third decade, estrogen has an anabolic effect on the osteoblast and an apoptotic effect on the osteoclast, increasing bone mineral acquisition in axial and appendicular bone. In the adult, estrogen is important in maintaining the constancy of bone mass through its effects on remodeling and bone turnover. Establishing a role for estrogen does not exclude a direct action of testosterone on bone in the human male (especially on cortical bone), but this action is less characterized than thought in the past and is relatively minor in comparison with the major effect of estrogen in the male. PMID- 11202220 TI - Estrogen treatment and estrogen suppression: metabolic effects in adolescence. AB - The metabolic consequences of reaching full reproductive maturity in humans involve not only growth hormone (GH) and insulin-like growth factor-I, but also the collaborative interaction of the gonadal sex steroids. Estrogen is critical for completing linear growth. It also inhibits bone resorption, decreases plasma lipid levels and serves as an antiatherosclerotic agent. Our studies show that, in low doses, estrogen increases GH production, increases calcium absorption and decreases bone turnover; however, unlike testosterone, estrogen has no effects as a protein-anabolic agent, at least at the whole body level. Studies of selective estrogen suppression, achieved using a potent aromatase inhibitor, show that estrogen is the main regulator of the gonadotropin axis. In boys, selective aromatase blockade may have a role in delaying epiphyseal fusion. Large placebo controlled trials will be required to study this effect further. PMID- 11202222 TI - Route-dependent endocrine and metabolic effects of estrogen replacement therapy. AB - The route of estrogen replacement therapy has a major impact on the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis. Estrogen administration by the oral, but not the transdermal, route reduces IGF-I and increases GH levels in postmenopausal women. This perturbation of the GH-IGF-I axis occurs with different forms of estrogen treatment, indicating that the dissociation of the somatotropic axis and concomitant increase in GH-binding protein levels are intrinsic effects of the oral route of estrogen administration. In clinical studies, oral estrogen reduced postprandial lipid oxidation, compared with transdermal estrogen. Oral estrogen was also associated with a reduction in lean body mass and an increase in fat mass, compared with transdermal estrogen. In contrast, the route of estrogen therapy had no impact on carbohydrate metabolism or the estrogen-induced increase in bone mineral density. The findings of route dependent changes in body composition add a new dimension to health considerations concerning estrogen therapy in postmenopausal women and may have significant implications for estrogen replacement therapy in young hypogonadal females. PMID- 11202223 TI - Telomerase and the cellular lifespan: implications of the aging process. AB - The aging process has multiple causes. However, there is now substantial evidence consistent with the hypothesis that (i) all normal mammalian somatic cells have a finite capacity to replicate and (ii) that gradual cell turnover throughout the lifespan of a mammal eventually exhausts this finite capacity. This results in a gradual accumulation of senescent (irreversibly post-mitotic) cells with increasing age. These cells display a radically different phenotype to their growing counterparts, which has the potential to compromise tissue function. Perhaps the best evidence for this is seen in Werner's syndrome, a rare genetic disease, in which patients display most of the features of accelerated aging, together with a profoundly compromised replicative lifespan in certain tissue lineages. Several classes of human cells are now known to count divisions by monitoring the progressive attrition of chromosomal ends (telomeres), leading to the activation of a p53-p21waf-dependent G1 checkpoint. Ectopic expression of telomerase has been shown to prevent senescence in several cell types and offers the potential for interventions in the aging process based on tissue engineering, gene therapy or homeografts. However, this telomere-driven senescence mechanism seems to be absent from rodents, which use telomere-independent means (perhaps based upon p14arf) to count divisions. Similar senescence pathways are now being reported in humans, and this, coupled with the demonstration of tissue-specific telomeric loss rates, has the potential to render strategies based on the use of telomerase dependent on the characteristics of the target tissue. Werner's syndrome may provide strong clues regarding the potential limitations and prospects of such future treatments. PMID- 11202224 TI - Human aging and progeria. AB - The notion that all aging is ultimately cell aging is a novel hypothesis and one with growing support. Recent studies in genetics and cell biology are consistent with this view. Criticism of the model is largely reflective of inadequate understanding of both the model itself and human pathology. Hutchinson-Gilford progeria is a segmental progeria that may well be an 'epigenetic mosaic' disease in which certain cell lines exhibit early cell senescence, while others are spared. The general cell senescence model of aging offers a consistent and elegant explanation of both human aging and progeria. More importantly, the model is not only testable but implies fundamental, novel and promising therapeutic avenues for both progeria and more typical age-related diseases. PMID- 11202225 TI - A role for the somatotropic axis in neural development, injury and disease. AB - This review article discusses the roles of the somatotropic axis in the growth and development of the normal central nervous system (CNS) and during recovery from brain injury. Classically, the actions of pituitary-derived growth hormone (GH) have been reported to be primarily mediated via the induction of hepatic insulin-like growth factor-I (IGF-I). GH receptors (GHRs), however, have now been identified in many body tissues and shown to have both endocrine and local actions, some of which are IGF-I independent. Within the brain, GHRs are widely located across a range of cellular phenotypes, yet little is known regarding their function or endogenous ligand. It is now becoming accepted that GH, like IGF-I, is integrally involved in the growth and development of the normal CNS. Following brain injury, IGF-I mRNA is induced, primarily within reactive microglia. The resultant IGF-I protein appears to have a dual role, first as an endogenous neurotropic and anti-apoptotic agent acting directly on stressed cells, and second as a prohormone for generation of the N-terminal tripeptide of IGF-I, glycine-proline-glutamate (GPE), and the resulting des-N-(1-3)-IGF-I, both of which have specific neuroprotective properties. Our work on deciphering the upstream regulators of injury-induced IGF-I has revealed that a GH-like substance is strongly upregulated after brain injury and specifically associated with stressed neurons and glia. Subsequent to this finding, GH administered centrally 2 hours after a hypoxic-ischemic brain injury in juvenile rats was found to provide significant neuroprotection, interestingly, in a spatiotemporal pattern distinct from the neuroprotection offered by IGF-I. The implications of these findings in regard to the growth, development and injury response of the CNS are discussed. PMID- 11202226 TI - Hypothalamic growth hormone-insulin-like growth factor-I axis across the human life span. AB - The activity of the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis undergoes marked variations across the human life span, mainly reflecting age related changes in the neural control of somatotroph function. IGF-I secretion generally reflects GH status, except in newborns, who secrete high levels of GH but low levels of IGF-I. Changes in the gonadal steroid milieu, particularly estradiol, play a major role in the enhanced activity of the GH-IGF-I axis at puberty and probably reflect further changes in the neuroendocrine control of somatotroph secretion. The change in responsiveness of somatotrophs to various stimuli, including GHRH, is not as marked as the spontaneous secretion of GH at puberty. However, in childhood, somatotrophs are unusually refractory to the somatostatin-mediated negative GH autofeedback mechanism. Normal children show normal responsiveness to the stimulatory influence of alpha-adrenergic and cholinergic agonists, galanin and arginine, but the activating effect of these stimuli on somatotroph secretion is reduced in elderly individuals, with the notable exception of arginine. Arginine potentiates both spontaneous and GHRH induced GH secretion to the same extent in normally growing children, adults and elderly individuals, indicating that the releasable pool of GH is generally preserved across the human life span. Thus, the reduction in spontaneous and GHRH induced GH secretion in the elderly probably reflects age-related changes in neurotransmitter control, leading to GHRH hypoactivity and absolute or relative somatostatin hyperactivity in the aged hypothalamus. Cholinergic impairment in the aging brain probably involves hypothalamic pathways and leads to decreased activity of the GH-IGF-I axis in normal and elderly individuals, as well as in individuals with premature brain aging. However, there is evidence indicating that age-related variations in the activity of the natural GH-secretagogue ligand(s) at the hypothalamic level could also play a role in the age-dependent changes in the GH-IGF-I axis. PMID- 11202227 TI - The lost voice: a history of the castrato. AB - Under the influence of testicular secretion, the male vocal cords increase in length by 67% in adult men compared with prepubertal boys, whereas in the female the increase is only 24%. This greater length and an increase in vocal cord mass is responsible for the lowering of pitch of the male voice during puberty. From the late 16th century, castration was carried out in Italy to preserve the unbroken male voice into adult life, but the high pitch was accompanied by fully grown resonating chambers and a large thoracic capacity, giving rise to the unique voice of the castrato. The initial stimulus for the production of castrati came from the Sistine Chapel in Rome, to provide singers for the complex church music of the time. The second reason was the coming of opera to Italy at the beginning of the 17th century. Boys were castrated between the ages of 7 and 9 years, and underwent a long period of voice training. A small number became international opera stars, of whom the most famous was Farinelli, whose voice ranged over three octaves. By the end of the 18th century, fashions in opera had changed so that the castrati declined except in the Vatican, where the Sistine Chapel continued to employ castrati until 1903. The last of the castrati was Alessandro Moreschi, who died in 1924 and made gramophone recordings that provide the only direct evidence of a castrato's singing voice. PMID- 11202228 TI - Immunofluorescence analysis of T-cell responses in health and disease. AB - The use of flow cytometry to study the functional responses of T cells by immunofluorescent staining for intracellular cytokines and other markers is a growing field of clinical interest. In this article, we describe methods for the rapid evaluation of T-cell responses to mitogens and specific antigens and explore how these assays might be valuable in various clinical settings. PMID- 11202229 TI - Recent developments in flow cytometry. AB - Flow cytometry has experienced considerable expansion of available parameters during the last years. Various new techniques that allow the direct analysis of antigen-specific lymphocytes by direct labeling with antigen or according to functional parameters following in vitro antigen stimulation will have enormous impact on immunological research, diagnosis, and therapy. This article concentrates on the basic principles and applications of these important technological developments in flow cytometry and focuses on the analysis of specific lymphocytes. PMID- 11202230 TI - Complexes of serum amyloid P component and DNA in serum from healthy individuals and systemic lupus erythematosus patients. AB - Serum amyloid P component (SAP) binds in vitro to DNA; based on findings in SAP deficient mice it was proposed that SAP's role is to handle chromatin and DNA, thereby preventing formation of anti-DNA antibodies. For the first time we have shown the presence of Ca2+-dependent SAP-DNA complexes, measured by ELISA, in sera from both healthy volunteers and systemic lupus erythematosus patients (SLE). The concentration of SAP-DNA complexes in SLE sera was significantly lower than in normal sera and particularly low in sera from patients with anti-DNA titers exceeding 50. The complexes were dissociated by the SAP ligand heparin and were not demonstrable in EDTA plasma. Normal sera showed similar capacity to form SAP-DNA complexes with both thymus and Escherichia coli DNA, whereas significantly lower amounts of complexes, in particular with E. coli DNA, were formed in SLE sera. SLE patients with moderate to high anti-DNA titers showed a significant negative correlation between serum SAP's binding of E. coli DNA and the anti-DNA titer. PMID- 11202231 TI - Autoantibodies to type VII collagen have heterogeneous subclass and light chain compositions and their complement-activating capacities do not correlate with the inflammatory clinical phenotype. AB - Epidermolysis bullosa acquisita and bullous systemic lupus erythematosus are blistering skin diseases characterized by IgG autoantibodies that predominantly target the noncollagenous domain 1 of type VII collagen, a skin basement membrane component. The basic immunologic events leading to the blistering processes in these diseases remains unclear. We defined the subclass and light chain compositions of the IgG autoantibodies in 15 patients, in order to gain insight into the blistering mechanism. Immunofluorescence correlated the patients' in vivo-bound and circulating antibasement membrane autoantibodies. Four eukaryotic recombinant proteins, including one full-length and three truncated noncollagenous domain 1 proteins generated by sequential deletion of C-terminal amino acids, were used to perform enzyme-linked immunosorbent assay to detect the patients' anti-type VII collagen autoantibodies. The majority of patients' autoantibodies contained both complement-activating and non-complement-activating IgG subclasses. The presence or absence of complement-activating IgG autoantibody subclasses did not correlate with the inflammatory or noninflammatory clinical phenotype. The majority of tested sera contained both kappa and lambda light chain autoantibodies. All sera that reacted to the full-length noncollagenous domain 1 also reacted to the smallest truncated protein containing the cartilage matrix protein and the first three fibronectinlike repeats. The patients' anti type VII collagen autoantibodies, likely to be polyclonal in nature, may contribute to the pathogenesis of the blistering process by both complement dependent inflammatory injury and complement-independent mechanical disruption of the anchoring function of type VII collagen. The N-terminal region of the noncollagenous domain 1 may contain an important antigenic epitope targeted by the IgG autoantibodies. PMID- 11202232 TI - A microfilament formation inhibitor, cytochalasin strongly enhances the low affinity Fc epsilon receptor II (CD23) expression on the human monocyte-like cell line, U937. AB - Enhancement of the low-affinity Fc epsilon receptor (CD23) expression by cytochalasin was analyzed on the human monocytelike cell line, U937. The CD23 expression on the U937 cells was enhanced at 24 hr after culture with cytochalasin B, D, or E, especially cytochalasin E having the most remarkable effect on it at the low concentration. This enhanced expression was found to be associated with a concomitant increase of a CD23 (about 45-kDa) protein on the U937 cells as assessed by Western blotting analysis. On the other hand, CD11a, CD18, CD31, CD49d, or CD54 was not markedly enhanced on the U937 cells by culture with cytochalasin E, although the mean fluorescence intensities (MFIs) of CD11a, CD18, and CD54 on U937 was partially up-regulated. Cell growth of U937 cultured with cytochalasin E was completely suppressed for 72 hr, but cell viability was sufficiently maintained (more than 95%). Soluble-formed CD23 (sCD23) also was released from the U937 cells at 24 to 72 hr after culture with cytochalasin E. In addition, the protein tyrosine kinase activity was detected in the U937 cells cultured with cytochalasin E for 24 hr using the enzyme immunoassay. Enhancement of the CD23 expression on the U937 cells at 24 to 72 hr cultured with cytochalasin E was sufficiently blocked by protein tyrosine kinase inhibitors herbimycin A and genistein, and a protein synthesis inhibitor, cychloheximide. On the other hand, protein kinase C inhibitors such as H-7 and H-8 had no effect on this CD23 expression. These results suggest that a mechanism underlying enhancement of the CD23 expression on the U937 cells cultured with cytochalasin E is mediated through tyrosine phosphorylation and protein synthesis. PMID- 11202233 TI - Exposure to topical bovine thrombin during surgery elicits a response against the xenogeneic carbohydrate galactose alpha1-3galactose. AB - Exposure of humans to topical bovine thrombin has been associated with development of antibodies against bovine and human coagulation factors and blood coagulation abnormalities. However, the nature of this humoral response is unknown. In this study, numerous glycoproteins in the topical bovine thrombin were found to contain the Gal(alpha1)-3Gal epitope, which is known to be highly immunogenic. More importantly, Gal(alpha1)-3Gal is recognized by natural antibodies that are found in all normal individuals and are known to effectively mediate complement activation and subsequent destruction of xenogeneic tissues. Thus, primary exposure of normal individuals to topical bovine thrombin is expected to result in an immediate immune reaction against that reagent. Further, following exposure to topical bovine thrombin, the levels of anti-Gal(alpha1) 3Gal IgG rose to levels tenfold greater than the average level of natural anti Gal(alpha1)-3Gal IgG in naive individuals. Thus, Gal(alpha1)-3Gal in topical bovine thrombin accounts for, at least in part, the highly immunogenic nature of this reagent. PMID- 11202234 TI - Low in vitro production of interferon-gamma and tumor necrosis factor-alpha in HIV-seronegative patients with pulmonary disease caused by nontuberculous mycobacteria. AB - We studied 32 HIV-seronegative patients with pulmonary disease caused by nontuberculous mycobacteria (NTM). Immunologic studies included lymphocyte subset analysis by flow cytometry, measurement of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) production following in vitro stimulation of diluted whole blood (DWB) and peripheral blood mononuclear cells (PBMC) by phytohemagglutinin (PHA), anti-CD3 as well as purified protein derivative of tuberculin (PPD), and in four cases with different amounts of the very mycobacterium, which caused disease in these patients. Data were compared to those of 30 HIV-seronegative patients with disease by Mycobacterium tuberculosis (MTb). Following alpha-CD3-stimulation of PBMC, NTM patients showed lower IFN gamma (P < 0.00005) and lower TNF-alpha (P < 0.02). For a subgroup of tuberculin skin test-positive NTM patients we found significantly lower PPD-induced IFN gamma releases in cultured DWB (P < 0.0002) and PBMC (P < 0.0004) compared to MTb patients. Data for PPD-induced TNF-alpha release for this subgroup were also significant (P < 0.001 and P < 0.05, respectively). The four NTM patients with poor PPD-induced IFN-gamma response hardly showed increased cytokine production on stimulation with their specific mycobacterium. The lower production capacity of IFN-gamma and TNF-alpha of NTM patients compared to the MTb patients points to an immunologic imbalance forming the basis for their increased susceptibility to pulmonary infections by nontuberculous mycobacteria. PMID- 11202235 TI - Elevation of transforming growth factor-beta1 is associated with recurrent miscarriage. AB - To investigate the significance of transforming growth factor-beta1 (TGF-beta1) in reproduction we have compared plasma levels in normal pregnant women and patients suffering miscarriages. We examined 188 normal pregnant women and 12 pregnant women with miscarriages. Eight women with severe recurrent miscarriages (mean +/- SD of previous number of miscarriages; 10.4 +/- 2.4 times) were also examined before conception; 34 nonpregnant women served as controls. Plasma TGF beta1 level increased with the gestational week and returned within the normal range 1 month after delivery. The levels among pregnant women with miscarriages (mean +/- SD; 2.44 +/- 0.83 ng/ml) were significantly higher than those of pregnant controls (1.74 +/- 0.95 ng/ml) of matched gestational weeks; levels among nonpregnant women with severe recurrent miscarriages were extremely elevated (4.1 +/- 3.04 ng/ml) compared to the control value (1.34 +/- 0.59 ng/ml). These data suggest that TGF-beta1 may be necessary to maintain pregnancy but also may be a risk factor for recurrent miscarriages. PMID- 11202236 TI - Cytokine analysis at the single cell level and lymphoproliferative responses to mycobacterial antigens in HIV-1 patients with successful virologic response to potent antiretrovirals. AB - Immunologic parameters, known to be grossly abnormal in HIV-1-infected subjects, were analyzed in 22 patients with sustained viral load suppression (<200 copies/ml) following long-term highly active antiretroviral therapy (HAART). Responses were compared with those from 18 HIV-seronegative healthy controls. Persistent phenotypic alterations in patients' blood mononuclear cells were minimal, though the percentages of lymphocytes that could be activated to produce interleukin-2 (IL-2) remained severely depressed. Using lymphoproliferative assays, a striking deficit in the capacity of patients to respond to the common mycobacterial antigens and particularly to recombinant heat-shock proteins paralleled the absence of responses to virus p24 antigen. In view of the important immunoregulatory role of stress proteins, these findings reveal profound functional deficiencies and persistent immune dysregulation in HIV-1 patients, despite successful HAART and a considerable recovery of CD4+ lymphocyte numbers. Rational immunotherapeutic approaches should be aimed to correct the characterized immune abnormalities. PMID- 11202237 TI - Umbilical cord blood transplantation in severe T-cell immunodeficiency disorders: two-year experience. AB - Hematopoietic stem cell transplantation is the treatment of choice for severe primary T-cell immunodeficiencies. When an HLA-identical sibling as the donor is not available, an alternative donor stem cell source is needed. In primary T-cell immunodeficiencies, T-cell-depleted HLA-haploidentical bone marrow transplantation has been particularly successful in reconstituting the immune system in many but not all of the severe T-cell immune deficiency disorders. This study reports the use of umbilical cord blood (UCB) stem cell transplantation in severe T-cell immune deficiency. Umbilical cord blood was evaluated as a stem cell source for immune reconstitution in children with severe primary T-cell immunodeficiency disorders, such as severe combined immunodeficiency syndrome (SCID), reticular dysgenesis, thymic dysplasia, combined immunodeficiency disease (CID), and Wiskott-Aldrich syndrome (WAS) when a matched sibling donor was unavailable. From 1/96 through 5/98, eight children received unrelated cord blood stem cell transplantation following a preparative regimen for the treatment of combined immunodeficiency diseases. The patients ranged in age from 2 weeks to 8 years. The cord blood units were 3/6 HLA antigen matches in two children. 4/6 in four children, and 5/6 in two child, with molecular HLA-DR mismatch in three of the children. The average time for neutrophil engraftment (absolute neutrophil count >500/mm3) was 12 days (range 10-15 days) and the average time for platelet engraftment (platelet count >20,000/mm3) was 36 days (range 24-50 days). A patient with reticular dysgenesis failed to engraft following her first transplant, but fully engrafted after a second unrelated donor cord blood transplantation. Five of six patients exhibited grade I graft-versus-host disease (GvHD). while one child had grade IV skin and gut GvHD. Immunologic reconstitution demonstrated that cord blood stem cell transplantation resulted in consistent and stable T-, B- and natural killer (NK) cell development. The kinetics of development were such that T-cell development occurred between 60 to 100 days. Initial T-cell engraftment consisted predominantly of CD45RO+, CD3+, and CD4+ T cells, and at 12 to 24 months changed to CD45RA+, CD3+, and CD4+ T cells, indicating de novo maturation of T cells. NK cell development occurred at approximately 180 days. B cells engrafted early, and study of functional B-cell antibody responses revealed that five of six patients in whom intravenous immune globulin has been discontinued have low detectable antibody responses to tetanus and diphtheria toxoid immunizations at 18 to 24 months posttransplantation. Unrelated umbilical donor cord blood is an alternative source of stem cells for transplantation in children with severe T-cell immune deficiency disorders when a suitable HLA-matched donor is not available and when a T-depleted haploidentical preparation is not beneficial. Benefits of UCB include rapid and reliable recovery of immune function, low risk of GvHD, and low viral transmission rate. PMID- 11202238 TI - Primary immunodeficiency diseases in Norway. AB - This study represents the first national epidemiological survey of primary immunodeficiency diseases in Norway. Uniform questionnaires were sent out in April 1998 to all hospital departments considered relevant. As of February 1999, a total of 372 patients have been registered, of whom 69 patients are deceased. With a population of 4.45 million people, the total prevalence of primary immunodeficiency diseases in Norway February 1, 1999 is 6.82 per 100000 inhabitants. Distribution between the main immunodeficiency diagnoses is (a) antibody deficiencies 50.8%, (b) combined deficiencies included other immunodeficiency syndromes 12.4%, (c) complement deficiencies 21.0%, (d) phagocytic disorders 6.7%, (e) and immunodeficiency associated with other congenital diseases 9. 1%. Compared to previous reports from other European countries, there is a smaller proportion of antibody deficiencies due to few IgA deficiencies registered and a large proportion of complement deficiencies due to many patients with hereditary angioedema. PMID- 11202240 TI - Deciding against defibrillator replacement: second-guessing the past? PMID- 11202241 TI - ICD replacement: a family-based medicine approach. PMID- 11202242 TI - Permanent explantation of implantable cardioverter defibrillators. AB - Although ICD therapy is seen as an irrevocable mode of therapy in most patients, a small number of patients do have their devices permanently explanted. The long term outcome in these patients has not been described. The purpose of this single center study was to evaluate the long-term outcome of patients whose ICD was explanted and not replaced and to propose clinical variables that can be considered when making the decision to discontinue therapy. Ten of 323 (3.1%) patients in our ICD registry had their devices permanently explanted or turned off between 1986 and December 1998. The devices had been in place for 39 +/- 31 months preexplant. No patient had received appropriate therapy prior to surgery, which was indicated for infection or lead fracture. All patients are alive and well 75 +/- 30 months postexplant with 1 (10%) patient requiring late reimplantation. We reviewed the English language literature describing ICD explanation without replacement. A total of 151 patients were reported in eight studies and were followed for up to 30 months postexplant. Excluding patients with terminal illness or heart transplantation 57.6% survived without reimplantation. In selected patients, after not using an ICD for a long period and when clinical circumstances justify, device therapy may be discontinued with some degree of safety. PMID- 11202239 TI - Soluble beta2-mu-associated and beta2-mu-free HLA class I heavy chain serum levels in interferon-alpha nonresponder chronic hepatitis C patients. Markers of immune activation, and response to antiviral retreatment. AB - The serum levels of soluble beta2-mu-associated and beta2-mu-free HLA class I heavy chains were determined in 28 interferon-alpha nonresponder chronic hepatitis C patients retreated with interferon-alpha plus ribavirin and in 70 healthy subjects. The baseline levels of beta2-mu-associated and beta2-mu-free HLA class I heavy chains were significantly higher in patients than in healthy controls (P = 0.001). The levels of beta2-mu-associated HLA class I heavy chains significantly increased in responder patients with respect to nonresponders at the third month of treatment (P = 0.03). At the sixth month of treatment and after 6 months of follow up the levels of beta2-mu-associated HLA class I heavy chains decreased in responder patients and increased in nonresponders. The levels of beta2-mu-free HLA class I heavy chains showed only minor changes during and after treatment. We suggest that the determination of hepatitis C virus RNA levels combined with soluble beta2-mu-associated HLA class I heavy chains, as a marker of immune activation, could identify interferon-alpha non responder chronic hepatitis C patients most likely to respond to a retreatment with interferon-alpha plus ribavirin. PMID- 11202243 TI - Autonomic nervous system activity before and during episodes of myocardial ischemia in patients with stable coronary artery disease during daily life. AB - Spectral analysis of heart rate variability (HRV) was used to assess changes in the autonomic nervous system (ANS) 10 minutes before, during, and 10 minutes after 110 ischemic episodes (IEs) in 38 patients (25 men, age 61 +/- 10 years) with stable coronary artery disease. In 26 of 77 diurnal IEs (07:00-22:59) there were no changes in the spectral indexes (LF and HF) during the study period. In the remainder there was an increase in the LF:HF ratio due to HF withdrawal that started before the onset of the IE. All 33 nocturnal episodes also showed an increase in the LF:HF ratio, which was due not only to HF withdrawal, but also to a simultaneous increase in LF. Although it is not the only cause, the ANS plays a significant role in triggering IEs during daily life in patients with stable coronary artery disease. The common factor in all such episodes is a gradual withdrawal of parasympathetic tone. PMID- 11202244 TI - Electrocardiographic criteria for diagnosis of irregular broad complex tachycardia with a high sensitivity for preexcited atrial fibrillation. AB - AF may appear as an irregular broad complex tachycardia (BCT) if atrioventricular conduction occurs via an accessory pathway (preexcited AF) or if bundle branch block (BBB), preexistent or rate related, exists in the His-Purkinje system (BBB AF). While BBB-AF is relatively benign, preexcited AF may herald sudden cardiac death. Hence it is important that the two conditions can be reliably distinguished. Yet, there is no preexistent algorithms for this purpose. Griffith et al. previously proposed a simple algorithm for a similar problem, that of distinguishing the two differential diagnoses for regular BCT: VT and SVT with BBB, on the basis that unless the QRS morphologies in V1 and V6 are absolutely typical of BBB, VT will be diagnosed. The authors propose an extrapolation of this principle to irregular BCT by stating that, unless the QRS morphologies in V1 and V6 are absolutely typical of BBB, preexcited AF will be diagnosed. Seventy five ECGs showing irregular BCT (41 preexcited AF and 34 BBB-AF) were shown to two fellows in electrophysiology who were given no other information and were instructed to diagnose preexcited AF unless the QRS morphology pattern was typical of BBB. Observer 1 achieved a sensitivity of 100% (41/41) and a specificity of 79% (27/34), while observer 2 achieved a sensitivity of 100% and a specificity of 85% (29/34). By QRS morphology pattern, an average sensitivity of 100% and specificity of 82% were achieved for the diagnosis of irregular BCT. The algorithm is simple and easy to implement and recommended for clinical use. PMID- 11202245 TI - Does an early increase in heart rate during tilting predict the results of passive tilt testing? AB - Head-up tilt testing is a useful but time-consuming procedure. If we could accurately predict the tilt testing results; we would be able to substantially shorten the duration of tilt protocol. To clarify the hypothesis that an early increase in heart rate (HR) during tilting can predict the passive tilt results in our protocol (80-degree angle for 30 minutes), we studied 115 consecutive patients (72 men, 43 women, mean age 46 +/- 19 years) who were clinically diagnosed with neurally mediated syncope. Twenty-nine (25%) patients had a positive tilt test (P group), whereas 86 (75%) patients had a negative test (N group). The early HR increase was defined as the maximum HR during the first 5 minutes of tilting minus the resting HR before tilting. The early HR increase was significantly higher in the P group (23.8 +/- 9.5 beats/min) than in the N group (17.5 +/- 8.2 beats/min, P = 0.0008), but it was negatively correlated with the tilt duration to positive response (r = -0.52, P = 0.0032) and the patient age in the entire study population (r = 0.62, P < 0.0001). Results of multiple regression analysis indicated that age, tilt result, and tilt duration were independently associated with the early HR increase. As a result, an early HR increase > or = 18 beats/min, the best apparent cut-off point obtained in our study, was a sensitive (100%) marker for prediction of a positive response at < or = 15 minutes of tilting, but it showed a low specificity (61%). In conclusion, an early HR increase during 80-degree tilting may be only predictive for a positive result < or = 15 minutes because it depends on the tilt duration to a positive response and patient age. PMID- 11202246 TI - Characteristics and results of epicardial pacing in neonates and infants. AB - The results of epicardial pacing in infants with isolated congenital complete atrioventricular block (CAVB) are reported. Thirty-four patients, aged 1 day to 20 months (22 patients < 1 month), were paced between 1988 and 1998. Thirty had bradycardia < 50 beats/min with symptoms in 12 patients, and 4 patients were paced because of associated ventricular ectopy or prolonged QT interval. In thirty cases, the electrodes were implanted through a left thoracotomy and connected to an abdominal generator; in four, the subxyphoid approach was preferred. Twenty-two children had dual chamber units. There was no operative death, but three patients died later of cardiomyopathy. Seven infants were reoperated for electrode displacement, infection, exit block, and pacemaker sensitivity. Chronic ventricular thresholds ranged from 0.3 to 2 V except in one case (4 V) and proper atrial sensing was lost in two cases. All children are doing well and the generator has lasted at least 5 years in 16 cases. In conclusion, epicardial pacing in infants with CAVB can be done with satisfactory results. There was no mortality in relation with pacing and thresholds have improved with the use of steroid-eluting electrodes. The deep location of the generator prevents cutaneous erosion and allows implantation of large units with a longer life duration. PMID- 11202247 TI - Diagnosis and ablation of atrial flutter using a high resolution, noncontact mapping system. AB - The ablation of atrial flutter can sometimes be time consuming and unsuccessful using conventional catheter techniques especially in patients with recurrences after previous ablation procedures. Simultaneous high resolution mapping from multiple sites may overcome some of the limitations. Therefore, a new high resolution noncontact mapping system was used for diagnosis and ablation of atrial flutter in 15 patients. The mapping system consists of a catheter-mounted multielectrode array, an amplifier, and a computer workstation. Far-field potentials recorded by the multielectrode catheter are amplified, digitized, and sampled at 1.2 kHz, and digitally filtered to construct high resolution activation maps during tachycardia. Ablation catheters can be steered to target sites without fluoroscopy. In 12 of the 15 patients the analysis of the activation sequence during tachycardia showed a counter-clockwise, and in 1 of 15 patients a clockwise, rotating wavefront using the isthmus as part of the reentrant circuit. In two patients no tachycardia could be induced. In 3 of the 15 patients with previous conventional ablation procedures the gap in the line of block in the isthmus region was identified and marked on the animation model. The isthmus in the right atrium was ablated and isthmus block verified by the mapping system in all patients. No complications were observed. No recurrences of atrial flutter occurred during follow-up of 4 +/- 1.7 months. The total procedure and fluoroscopy time was 171 +/- 50.0 minutes and 24 +/- 12.7 minutes, respectively. In conclusion, the use of the new high resolution noncontact mapping system in patients with right atrial flutter is safe and highly effective. In patients with previously failed conventional ablation procedures the use of a noncontact mapping system may facilitate the identification of the gap in the line of block in the isthmus region and reablation of atrial flutter. PMID- 11202248 TI - Safe and effective placement of two bipolar silicone leads in the cephalic vein using a hydrophilic guidewire and a split introducer. AB - The cephalic vein (CV) is preferable to the subclavian vein for implanting permanent pacing leads because of fewer complications. Unfortunately, this access is unusable in a substantial number of patients. This prospective study evaluates a technique to increase CV access for the placement of two silicone bipolar leads used in DDD pulse generator implants. A standard cephalic cutdown was performed under local anesthesia and a hydrophilic guidewire (HGW) threaded in the CV. The first (ventricular) bipolar lead was then introduced and positioned. When possible, introduction of the second (atrial) lead followed the same direct access. A failed introduction led to a modified procedure (MP) relying on a "split" introducer (8-9 Fr Plastimed) advanced with a circular motion over the HGW, then removal of the dilator, removal of the HGW, insertion of the pacing lead into the sheath with placement in the right atrium, followed by sheath withdrawal. Over an 18-month period, 90 consecutive patients had DDD pacemakers implanted. The CV was accessible in 76 (84.5%) of 90 patients and the direct introduction of the ventricular lead was obtained in 74 (97.4%) of these. Atrialization proceeded as follows: direct access CV in 14 (18%) of 76 patients, MP access in 54 (71%) of 76 patients, and MP failure in 8 (11%) of 76 patients. Overall, this approach allowed cephalic dual insertion in 68 (89%) of 76 patients. In conclusion, the modified procedure presented in this study allows a dual catheterization with bipolar leads in 89% of patients when a CV is available. This significantly improves the success rate for dual bipolar lead implants in this configuration. PMID- 11202249 TI - Passive-fixation J-shaped versus straight leads in atrial position: comparison of efficacy and safety. AB - To compare the efficacy and safety of straight and J-shaped passive-fixation atrial leads we retrospectively analyzed the results of 100 consecutive implantations of atrial leads at one institution. There were seven cases of upgrades of VVIR to DDDR systems and in one case an active-fixation lead was chosen as a primary approach. These eight patients were excluded from the analysis. The final study group consisted of 92 cases (69 DDDR, 23 AAIR), 69 were J and 23 straight leads. The stimulation threshold, slew rate, impedance, P wave amplitude, and procedural time did not differ significantly between the two types of leads used. During the long-term follow-up of 6-53 months (30 +/- 11.9 months), replacements using active-fixation leads were required in two patients with straight leads and three patients with J leads (P = NS). In addition, one J lead showed signs of damage (impedance > 3,000 Ohm). Long-term follow-up values of the stimulation thresholds and P wave amplitudes did not differ between the groups (P = NS). Transesophageal echocardiography performed in 13 patients revealed a trend toward more distal placement of straight leads within the right atrial appendage. In conclusion, J-shaped leads do not seem to be superior to the straight leads for atrial implantations. PMID- 11202250 TI - Improved differentiation of the ventricular evoked response from polarization by modification of the pacemaker impulse. AB - The Autocapture feature, implemented in the Microny and Regency pacemakers of St. Jude Medical, continuously controls the effectiveness of ventricular stimulation by detection of the evoked response. Proper sensing of this signal depends on the magnitude of the polarization, which should be minimal. Therefore, the conjunctive use of low polarization electrodes is recommended. Further, the pacing impulse of these pacemakers has a biphasic waveform consisting of a stimulus followed by a fast discharge pulse. This study compares polarization of a modified pacing impulse with the default pacing impulse, and its effect on the ability to activate the Autocapture function when used with different types of electrodes. In 45 patients, acute measurements of the polarization and the evoked response were performed at random on the modified pacing impulses of a custom designed Regency and on the default stimuli of a standard Regency. The following bipolar leads were used: 20 Medtronic 4024 CapSure, 12 Pacesetter 1450T, and 13 Pacesetter 1470T. Using the default pacing impulse, polarization and evoked response were significantly larger with the Medtronic 4024 CapSure compared to the low polarization leads. The polarization to evoked response ratio was more frequently acceptable for activation of the Autocapture with the Pacesetter leads. In all leads the modified pacing impulse was characterized by significantly smaller polarization with the most prominent reduction in the Medtronic 4024 CapSure. The differences in the pacing impulse did not affect the evoked response. With the programmability of the fast discharge pulse, the requirements to activate the Autocapture function were fulfilled in 29 (94%) of 31 patients with the modified pacing impulse, compared to 22 (71%) of 31 patients with the standard pacing impulse. The modified pacing impulse decreased the "polarization to evoked response" ratio, and by that improved the conditions for activation of the Autocapture function. PMID- 11202251 TI - Atrioventricular nodal versus atrioventricular supraventricular reentrant tachycardias: characterization by an integrated Doppler electrophysiological hemodynamic study. AB - During reentrant supraventricular tachycardias involving the atrioventricular node (AVN-SVT) or an AV bypass tract (AV-SVT), atrial pressure increases. While in AVN-SVT this increase relates to atrial contraction during ventricular systole, the mechanism remains unclear in AV-SVT. This study sought to clarify this mechanism. During 11 AVN-SVTs and 9 AV-SVTs, anterograde flow through the AV valves and retrograde flow in the pulmonary and hepatic veins were studied by pulsed-wave (PW) Doppler measuring the time interval between the ECG-R wave and (1) the end of venous retrograde flows, and (2) the beginning of valvular anterograde flows. The positive or negative difference between these two time intervals guided recognizing the atrial contraction against open or closed AV valves. Intracavitary pressures and cardiac index were also measured. During AVN SVTs, venous retrograde flows always ended before the anterograde valvular flows, indicating atrial contraction against closed AV valves. During AV-SVTs, pulmonary retrograde flow ended before the beginning of mitral anterograde flow in five cases, began before but ended during the anterograde flow in three cases, and overlapped to the anterograde flow in one case. A corresponding behavior was observed at the right side of the heart. In both SVTs, atrial pressures increased and end-diastolic ventricular pressure and cardiac index decreased similarly. During AVN-SVT, the atrial contraction always occurs against closed AV valves, and during AV-SVT it generally occurs against totally or partially closed AV valves, explaining similar atrial pressure and cardiac index changes in both SVTs. PMID- 11202252 TI - A comparative study on the behavior of three different automatic mode switching dual chamber pacemakers to intracardiac recordings of clinical atrial fibrillation. AB - Automatic mode switching (AMS) allows patients with dual chamber pacemakers who develop paroxysmal AF to have a controlled ventricular rate. The aim of this study was to (1) compare the rate-controlled behavior of three AMS algorithms in response to AF, in terms of speed and stability of response and resynchronization to sinus rhythm, and (2) compare the influence of pacemaker programming on optimal mode switching. We studied 17 patients (12 men, 5 women; mean age 59 +/- 15 years) who developed AF during electrophysiological study. Unfiltered bipolar atrial electrograms during sinus rhythm and AF were recorded onto high fidelity tapes and replayed into the atrial port of three dual chamber pacemakers with different mode switching algorithms (Thera, Marathon, Meta). The Thera pacemaker uses rate smoothing, and mode switches occur when mean sensed atrial rate exceeds the predefined AMS rate (MR). Marathon mode switches after a programmable number of consecutive rapid atrial events (NR). Meta DDDR monitors the atrial rate by a counter for atrial cycles faster than the programmed AMS rate. It increases or decreases the counter if the atrial cycle length is shorter or longer than the programmed AMS interval, respectively. Mode switch occurs when the AF detection criteria are met (CR). A total of 260 rhythms were studied. NR was significantly faster than MR and CR (latency 2.5 +/- 3 s vs 26 +/- 7 s vs 15 +/- 22 s, respectively, P < 0.0001). During sustained AF, MR resulted in the most stable and regular ventricular rhythm compared to NR or CR. In CR, ventricular rate oscillated between AMS and atrial tracking (cycle length variations: 44 +/- 2 s vs 346 +/- 109 s vs 672 +/- 84 s, P < 0.05). At resumption of sinus rhythm, MR resynchronized after 143 +/- 22 s versus 3.4 +/- 0.7 s for NR and 5.9 +/- 1.1 s for CR, resulting in long periods of AV dissociation when a VVI/VVIR mode is used after AMS. Programming of atrial refractory periods did not affect AMS response, although the speed of AMS onset can be adjusted by programming of onset criteria in the Meta DDDR. AMS algorithms differ in their ability to handle recorded clinical atrial arrhythmias. The rapid-responding algorithm exhibits rate instability, whereas slow responding algorithm shows a long delay in response and risk of AV dissociation. Thus different instrumentation of AMS may have clinical implications in patients with dual chamber pacemakers who develop AF. PMID- 11202253 TI - Initial low temperature setting in radiofrequency catheter ablation of Wolff Parkinson-White syndrome. AB - Previous studies have shown that with low temperature testing for RF ablation of arrhythmias, unnecessary irreversible myocardial lesions may be avoided. In children admitted for RF ablation from June 1996 to May 1999, we evaluated the method of an initial temperature setting of 50 degrees C for a maximum of 10 seconds. If accessory pathway block occurred, the temperature setting was immediately increased to 70 degrees C and continued for 45-120 seconds (group 1). If accessory pathway block did not occur after several attempts, subsequent attempts were made with initial settings at 70 degrees C-80 degrees C at the same or different sites (group 2). Eighty patients with Wolff-Parkinson-White syndrome (mean age 11 +/- 4 years) were treated using this method. Twelve patients were excluded for various reasons. Of the remaining 68 patients, 52 (76%) had successful block of the pathway at 50 degrees C; 16 patients demonstrated block only at the higher temperature setting of 70 degrees C-80 degrees C. There were no statistically significant differences between these two groups in terms of age, weight, and location of accessory pathways. Unsuccessful 50 degrees C test ablation attempts were 1.6 +/- 2.4 in group 1 and 3.1 +/- 2.9 in group 2 (P = 0.04). Total unsuccessful attempts were 1.6 +/- 2.4 in group 1 and 8.1 +/- 7.1 in group 2 (P = 0.001). The time from application of RF energy to the time of AP block in group 1 was not significantly different from group 2. In the majority of children, successful RF ablation can be achieved by using a temperature setting of 50 degrees C, then 70 degrees C. This will prevent unnecessary permanent injury at unsuccessful attempt sites. PMID- 11202254 TI - Is dual site better than single site atrial pacing in the prevention of atrial fibrillation? AB - Long-term prevention of atrial fibrillation is not constantly realized by single site right atrial pacing, and the beneficial role of multisite atrial pacing is still being studied. Accordingly, we compared the effectiveness of dual site and single site atrial pacing in 83 patients (50 men, 33 women, aged 69 +/- 10 years), who received a DDD device for primary sinus node dysfunction or bradycardia with documented atrial fibrillation. Inclusion criteria for dual site pacing were a sinus P wave > or = 120 ms and at least two episodes of documented paroxysmal AF in the 6 months preceding implantation. Dual site atrial pacing (high right atrium-coronary sinus ostium) was performed in 30 cases, and was compared to 53 single site paced patients, 21 with a P wave > or = 120 ms and 32 with a P wave < 120 ms. The basic pacing rate was programmed at 68 +/- 4 beats/min (range 60-75 beats/min). Sinus P wave (133 +/- 20 vs 95 +/- 9 ms; P < 0.001), paced P wave (107 +/- 14 vs 99 +/- 15; P < 0.05), number of antiarrhythmic drugs used (2.4 +/- 1.2 vs 1.6 +/- 1.5, P < 0.05), and the duration of symptoms (8.1 +/- 4.5 vs 3.8 +/- 2.4 years; P < 0.001) were significantly higher in dual site patients. The other characteristics were similar. During the follow-up of 18 +/- 15 months (range 3-30 months), paroxysmal AF was documented in 33 patients. Among these patients, 13 developed permanent AF following at least one episode of paroxysmal AF. When comparing dual site patients and single site patients with a P wave duration > or = 120 ms, paroxysmal AF incidence was lower in the dual site group (9/30 patients vs 15/21 patients, P < 0.01), as well as permanent AF (1/30 patients vs 8/21 patients, P < 0.01). By contrast, comparison between dual site patients and the group of single site patients with a P wave duration < 120 ms did not evidence any significant differences in paroxysmal (9/30 patients vs 9/32 patients) and permanent (1/30 patients vs 4/32 patients) AF incidences. Dual site seems better able than single site atrial pacing to improve the natural history of patients with a prolonged P wave, reducing the incidence of paroxysmal and permanent AF. No benefit could be expected in patients with a normal P wave duration. PMID- 11202255 TI - Inferior vena cava loop of the implantable cardioverter defibrillator endocardial lead: a possible solution of the growth problem in pediatric implantation. AB - The ICD is an important treatment option in adults and children with life threatening tachyarrhythmias. The possibility of lead displacement caused by growth and the lack of dedicated leads and devices poses special problems in pediatric ICD implantation. We describe our experience in three children in whom we left a redundant lead loop within the inferior vena cava (IVC) is allow for further growth. Since February 1998, three children underwent ICD implantation at our institution. A lead (screw-in) was advanced into the right ventricular apex, and a loop was created in the IVC by progressively withdrawing the stylet and pushing in the lead. Satisfactory sensing and pacing threshold values were obtained and a successful single 16-J defibrillation test was performed. No complications were encountered. After a mean follow-up of 16 months, with a mean increase in body weight and height of 4.1 +/- 0.5 Kg and 6.3 +/- 0.4 cm, respectively, chest X ray showed some release of additional lead length, in the absence of dislodgments, while significant changes in pacing/sensing parameters were not found. In conclusion, the creation of a loop within the IVC allows the lead to adjust for growth in children receiving an ICD. This approach is feasible and safe. PMID- 11202256 TI - Lead noise with an active-fixation defibrillation lead. AB - Inappropriate detection and therapy is the most common adverse effect of implantable cardioverter defibrillator therapy. One mechanism is lead artifact, which usually presents late and is due to stress and fatigue of the lead components. Our experience with a defibrillator lead (Endotak Endurance EZ leads, Models 0154/0155/0156) and its method of active fixation is described. Of 20 implants with this lead, four patients were found to have noise that resulted in inappropriate detections in three. No patient received therapy as a consequence of these detections. The artifact appeared soon after implant and resolved in three of four cases by 4 weeks. None of the 16 remaining patients developed noise after this time. This is a unique lead problem that resolves with time, but it may result in inappropriate therapies and difficult management decisions in high risk patients with ventricular arrhythmias. PMID- 11202257 TI - The first reports of electrical multisite ventricular activation in humans. PMID- 11202258 TI - Tachycardia induced changes of atrial electrophysiological properties. PMID- 11202259 TI - Long RP tachycardia with RR alternation. PMID- 11202260 TI - Iatrogenic ventricular tachycardia from endocardial pacemaker late after repair of tetralogy of Fallot. AB - A 34-year-old woman, who had undergone radical repair for tetralogy of Fallot at the age of 8 years, was left with moderate-to-severe pulmonary regurgitation. VT developed after endocardial pacing for symptomatic pauses and atrial flutter. The possibility that the new VT originated from the apical endocardial lead was suggested by the unusual morphology of the VT, which was similar to paced. Surgical removal of the lead, which was deeply embedded at the same time as a pulmonary valve was replaced, cured the arrhythmia. This unusual cause of VT highlights possible risks associated with setting up a dangerous reentry circuit by inserting a right ventricular endocardial pacemaker lead. PMID- 11202261 TI - Permanent pacing from a left ventricular vein in a patient with persistent left and absent right superior vena cava. AB - Persistent left superior vena cava with coexisting absent right superior vena cava is rare with less than 150 cases in the literature. Various techniques for pacemaker implantation have been described in this situation. We report a 40-year old man with sinus and atrioventricular nodal dysfunction who underwent dual chamber pacemaker implantation. We elected to implant the ventricular electrode down a left ventricular branch of the coronary sinus and the lead is stable at 4 month follow-up. PMID- 11202262 TI - Cardiopulmonary resuscitation during coronary vasospasm induced by tilt table testing. AB - A 65-year-old man presented to our institution with recurrent episodes of early morning chest discomfort and near syncope. An ergonovine provocation test documented a diagnosis of coronary vasospastic angina. Using our investigation of the syncope, a head-up tilt table test provoked a severe episode of coronary vasospasm that resulted in a life-threatening cardiac event. The present case reminds us that an elevation of ST segments on the electrocardiogram during tilt testing should be promptly managed as an attack of coronary vasospasm. PMID- 11202263 TI - Laser-assisted explantation of trapped Port-A-Cath. PMID- 11202264 TI - Runaway pacemaker syndrome and intermittent nonoutput as manifestations of end of life of a VVI pacemaker. AB - A case of a runaway pacemaker with intermittent nonoutput failure of a VVI Intermedics pacemaker is presented. This is the first report of such a phenomenon in that type of pacemaker with no apparent reason other than approaching battery end-of-life. The reported case warrants a close follow-up of patients with the same type of device. PMID- 11202265 TI - Cumulative 23-year index. Volumes 1-23, 1978-2000. PMID- 11202266 TI - Surgery for primary hyperparathyroidism. AB - OBJECTIVE: To define the role of surgery for organic primary hyperparathyroidism and to evaluate the diagnostic and operative methods applied. DESIGN: Retrospective, non-randomized, non-blinded evaluation. Case series. SETTING: Tertiary referral center. Department of Surgery. SUBJECTS AND METHODS: The report documents experience in surgical management at a single institution of 312 patients with primary (and 498 patients with secondary) hyperparathyroidism in a period from 1974 to 2000. Patient symptoms, clinical features, diagnostic and localization methods, operative management, and postoperative results were evaluated by retrospective medical record review with special attention to surgical management strategy. RESULTS: Of 321 patients with primary hyperparathyroidism 312 underwent 348 operations. There were 312 primary procedures and 36 multiple reoperations on 25 patients. The permanent success rate for primary (312) operations was achieved in 287 patients (92%). The permanent success rate for 36 secondary reoperations was achieved in 19 out of 25 reoperated patients (76%). The overall full recovery was obtained in 306 operated patients (98%). There were no postoperative emergency reoperations. There were 2 postoperative hospital deaths (0.6%) of patients with sustained hypercalcemic crisis after excision one cervical adenoma, but functioning second one in mediastinum. PMID- 11202267 TI - Current management of thyroid cancer--a change of therapeutic strategy over the last 20 years. AB - A radical change of epidemiological structure of thyroid cancer incidence in Poland has been reported for few years. The total incidence of thyroid cancer is successively increasing, mostly in form of well differentiated thyroid cancer, especially papillary cancer. The diagnostic and therapeutic approach to thyroid cancer have also changed. Ultrasound guided fine needle aspiration has become the first choice procedure in diagnostics of thyroid cancer. Careful assessment of prognostic factors is no longer helpful in choice of selective surgical procedure in thyroid cancer as elective total thyroidectomy is widely recommended. In well differentiated thyroid cancer a complementary treatment with radioiodine is mandatory in most cases. Own experience in treatment of thyroid cancer presented in the paper is based on over 520 consecutive patients with thyroid cancer treated in a single department specialised in endocrine surgery during last 20 years. Successive changes in epidemiological structure of thyroid cancer incidence as well as the evolution of diagnostic and therapeutic algorithm in thyroid cancer are presented in details. Radical surgical treatment of thyroid cancer is still a fundamental part of a complex treatment of thyroid cancer. PMID- 11202268 TI - Radioiodine therapy: its role in the combined treatment of differentiated thyroid carcinoma. PMID- 11202269 TI - The history of development and perspectives of breast cancer surgery. PMID- 11202271 TI - Life saving surgery in polytrauma patients. AB - Life saving surgery is the surgery which has to be performed during the acute or reanimation period (1 to 3 h) and during the primary or stabilisation period (first day surgery). During the reanimation period lifethreatening conditions are identified and management is begun simultaneously. Many trauma surgeons talk about the first "golden hours" as the time interval starting immediately after the injury when rapid intervention will save lives and a lack of intervention will result in life loss. Most common, these critical conditions are exsanguinating hemorrhage, acute pump failure, obstruction of airways, mechanical failure of ventilation or severe brain damage with tentorial herniation. During this period, the following acts are necessary: surgical access to live support systems (airway, veins), life saving decompression of body cavities, resuscitative thoracotomy, control of exsanguinating external hemorrhage and control of exsanguinating hemorrhage into the body cavities. The primary or stabilisation period starts when vital functions stabilise. This period consists of further diagnostic procedures and treatment of injuries that are not directly life-threatening, but which may become life endangering or severely disabling if not treated promptly. The priorities of the surgical treatment are: brain injuries, eye- and facial injuries, progressive compression of the spinal cord, visceral injuries, musculoskeletal injuries. By improving prehospital care, rapid transport and last but not least immediate life saving surgical treatment preventable deaths can be reduced from 20-30% to 2-9% (5). PMID- 11202270 TI - Lymph node mapping and sentinel lymph node biopsy for evaluation of axillary lymph node status in early invasive breast cancer. Our experience. AB - The Authors show their preliminary experience with the sentinel lymph node biopsy (SLNB) in clinical early invasive breast cancer (T1N0). During a period of 15 months, forty-two patients were submitted to SLNB upon Tc99-colloid albumin injection and SLN identification by lymphoscintigraphy. The middle number of lymph nodes found in the SLNB was 1 (1-3), whereas the middle number of lymph nodes identified in level I/II ALND specimens was 15. The SLN was identified with success in all cases (100%). The axilla was positive for metastasis in 4/42 cases. The SLN was positive in all four cases in which nodal metastasis was identified. The negative predictive value of SLN was 100%. The SLN was the only site of metastasis in 3/4 cases. The SLN pathological status accurately reflected the lymphatic basin status, but further investigation is needed to define the optimal timing of colloid injection and method of examination of the SLN. PMID- 11202272 TI - Modern approach to management of patients following major trauma. AB - Trauma remains one of the three main causes of death all over the world. In Poland severe trauma is also an important public health problem which should be fully recognised in the changing system of our health service. There is a growing understanding and interest in the integration of pre-hospital, in-hospital and rehabilitation services taking part in the management of trauma patients. The importance of emergency medicine departments has been found valuable in Western countries and should be promoted by all means in our country. Certain recommendations of treatment of patients following severe trauma have been discussed concerning anti-shock therapy, diagnostic and operative management in polytraumatized patients with major head trauma, thoracic and abdominal trauma and also operative stabilization of fractures of bones. It has been concluded that in our country, especially in bigger cities, patients following major trauma should be treated in specially designed units (centers) integrated with emergency medicine departments providing competent intensive therapy and surgical interventions of well trained trauma teams introducing optimal modern trauma algorithms. PMID- 11202273 TI - Colorectal war injuries. PMID- 11202274 TI - Trauma care for the year 2000. AB - Trauma is a third killer of modern european and world societies. Everywhere in Europe there is the great necessity of having an efficient emergency prehospital and hospital trauma care organization which will reduce mortality and invalidity of the trauma critical patients. Three objectives are the most important: 1) defining of the lines guide (e.g. ALTS) 2) continuous education and training of education the medical and paramedical operators (doctors, nurses, technicians, paramedics) 3) applying the method on organization and structural base. According to statements of Council of Europe, European College of Surgeons, E.A.E.S., it has been affirmed "In addition to General Surgery training for the surgeons should require a complementary training in Emergency Surgery either" concurrently or consecutively. As a first suggestion; the idea is to create centers of excellence fully equipped with all modern facilities and well trained medical staff. Those centers should be spread over the Europe and available round tho clock. Those centers should be supervised by a trained Emergency Surgeons with the indispensable aids and cooperation of anesthesiologist. The other very important factor is optimalization of patients transport towards the suitable trauma care center. Emergency Surgical Training should be established on three levels namely; 1) within the undergraduate medical curriculum 2) complementary training in emergency surgery during the general surgery specialization 3) additional theoretical and practical training for emergency nurses. There are many cultural and organizational differences among the "old and new" European Countries. The most important and special objective is the evolution of a correct and equal education in training care in order to improve our situation. PMID- 11202275 TI - Renal trauma. PMID- 11202277 TI - Advances in the treatment of severe fecal incontinence. PMID- 11202276 TI - One-day surgery in multiple trauma patients. AB - The aim of the authors was evaluation of influence of progress in MT procedures, particularly on final results of treatment, with special attention to aggressive one-day surgery, including definitive orthopaedic operations. The study is based on own material from the 2-nd Department of Surgery of the Jagellonian University. From almost 3000 victims of accidents with multitrauma (MT), who were treated between 1968 and 1997, 932 patients were selected. They were treated in consecutive 2-year periods in a 5-year cycle, starting from 70/71 up to 95/96. From 1987, the patient material has been prospectively coded. A steadily growing number of MT patients were stated with the only exception in 85/86 period. Traffic accidents were the major cause of injuries in over 2/3 of victims and men were predominated. Time lapse from accident to arrival became shorter. Severity of injuries was growing steadily as well: from 21.55 to 26.17 points of ISS (Injury Severity Score). At the same time percentage of operated increased from 34.88 to 47.62, and length of stay decreased from 23.45 to 19.79 days. The most significant finding, however, was the fact that deep-set objective increase of trauma severity, mortality rate decreased twofold--from 29.07% at the beginning to only 14.85% at the end. The improvement resulted from progress in diagnosis and treatment of MT patients. Implementation of diagnostic peritoneal lavage, refurbishing of our intensive care unit, installment of computed tomography in the cases of head injuries, gradual introduction of early stabilisation of major fractures and routine early anticoagulant prophylactic and hyperalimentation as well as full standardisation of the therapeutic process--all these were the "mile stones" which assured reaching such satisfactory results. PMID- 11202278 TI - Enzyme therapy in patients with advanced colorectal cancer. PMID- 11202280 TI - Nutrition in cancer. PMID- 11202279 TI - Surgical and combined treatment of gastric cancer--own experience. AB - PURPOSE: In Poland, as well as all over the world, gastric cancer is still among the leading causes of mortality and morbidity from malignant diseases. Many attempts were made to improve the results of the treatment. In this paper we present our 25-year experience in this field. MATERIAL AND METHODS: From 1977 to 2000 in the Clinical Department of Surgical Oncology, Medical University of Lodz, we treated 353 patients (males 63%; females 37%) with the diagnosis of gastric cancer, confirmed histologically. We analysed the age of patients, location of primary tumor, histologic type, stage of the disease, type of surgery, type of reconstruction of GI tract, type of adjuvant therapy and survival. RESULTS: In patients with the disease in stage I and II according to UICC Fielding classification, the best results were achieved. Five year survival reached 76% which means that early recognised gastric cancer may be cured. However, patients from this group constituted only 6.7% of all the treated population. In patients with stage III disease, 5 year survival was 34.5%. In patients with IVA stage of the disease (72 cases), in whom only cytoreductive-palliative surgery was performed, 5-year survival was 16.7%. No patient with IVB stage of the disease (purely palliative procedures performed) survived 5 years. Significant improvement of distant results was, observed in patients receiving EAP as an adjuvant therapy (25.1% of 5-year survivors) in comparison to control group patients treated solely with surgery (18.2% of 5 year survivors). In 97 patients after total gastrectomy, significantly lower complication rate was observed in patients in whom intestinal pouch was created (Hunt-Lawrence) than in patients in whom the pouch was not created (Roux-Y, Engel-Graham). CONCLUSION: In our opinion, we should consequently implement guidelines known as the "Polish Consensus of Gastric Cancer Treatment", like extensive radical stomach resection (whenever possible) with regional lymphadenectomy and adjuvant therapy. PMID- 11202281 TI - Double-blind pilot-study on the efficacy of enzyme therapy in advanced colorectal cancer. AB - All tested variables showed a tendency in favor for Wobe-Mugos E therapy as addition to standard therapy. Enzymes improve the quality of life by reducing cancer disease typical symptoms, they reduce side effects of chemo-/radiotherapy and they have a potential of prolonging life (preliminary data only). PMID- 11202282 TI - Primary suture vs. T-tube after common bile duct exploration (our 25 years of experience). AB - PURPOSE: The aim of our retrospective study is to return confidence in primary suture (PS) procedure after common bile duct exploration (CBDE). The first CBDE was performed in 1884 using PS. T-tube drainage was introduced 10 years later, and PS procedure has been abandoned today. MATERIAL AND METHODS: In the course of the last 25 years (1974-1999 period) 4971 cholecystectomy have been performed with 682 (13.5%) CBDEs. There have been 201 (30%) T-tubes, 238 (34%) PS, 219 (32%) biliodigestive anastomosis (BDA) and only 24 (3%) papillotomies (PT) performed. Intraoperative choledochoscopy has been performed as a routine intraoperative method, too. RESULTS: In 439 patients, operated either using PS or T tube procedure were as follows: retained stones 6:16 (2.5%:8%), billiary complications 4:14 (1.6%:7%) and mortality 1:6 (0.3%:3%), respectively. PS is a significantly less expensive procedure, spending less medicaments, i.v. fluids, X ray and laboratory tests, with a shorter postoperative hospital stay. CONCLUSION: PS is unjustly abandoned operative procedure. The advantages of the method are lower complications rate as well as lower costs. Present progress in surgery, less operative aggression, must be considered, especially during laparoscopic cholecystectomy. PMID- 11202283 TI - Palliative treatment of gastrointestinal tumors. PMID- 11202284 TI - Critical overview of the current status of treatment of pancreatic cancer: oncological point of view. PMID- 11202285 TI - Long-term results of pancreatic cancer surgery. AB - Despite of growing incidence of pancreatic cancer and dynamic development of modern diagnostic methods, long-term treatment results are still unsatisfying. The aim of the study is the assessment of long-term outcome of pancreatic cancer surgery. Group of 621 patients hospitalized between 1972-1999 was analyzed. Pancreatic resection was performed in 34.1% (n = 212) patients, and in 65.9% (n = 409) cases a palliative bypass procedure was carried out. Increased number of resective procedures (from 6.2% to 40.1%) in the recent years was observed with lower perioperative mortality rates (from 20% to below 5%). The analysis of the long-term results of surgical treatment for pancreatic cancer showed significant improvement of the overall 5-year survival from 4.2% to 17.1% in the recent years. Based on the carried out analysis the authors conclude, that pancreatic cancer surgery performed by the experienced surgeon improves long-term results lowering to minimum the rates of complications. PMID- 11202286 TI - Extrahepatic cholestasis: are there any "leftovers" for surgeons? PMID- 11202287 TI - Renal failure in acute pancreatitis. Timing of dialysis and surgery. AB - Despite the progress in intensive care treatment the ongoing systemic inflammatory response syndrome (SIRS) in patients with severe pancreatitis (SP) and renal failure (RF) is associated with high mortality. The aim of this lecture is to outline the knowledge drawn from literature and personal experience and to re-evaluate the management strategy of SP patients whose clinical course is complicated with impairment of the renal function. INCIDENCE, RISK FACTORS AND OUTCOME: Impaired renal function can be observed in 14-43% of patients with SP mostly in combination with other organ system failure. SIRS is the main culprit in the pathologic process. Extent of necrosis does not correlate with derangement of the renal function, however, infection is a serious risk factor. Mortality reaches 71-84% in patients with SP and RF, which requires dialysis. Risk factors highly associated with RF and detrimental outcomes in SP patients are advancing age, prior chronic disease, cardiovascular and pulmonary failure, mechanical ventilation, hypotension, oliguria, coma, and jaundice. SP is associated with increased bowel permeability, impaired visceral perfusion, retroperitoneal oedema and increased intraabdominal pressure, which can directly affect the renal function as consequence of the acute abdominal compartment syndrome (AACS). TREATMENT: Early aggressive resuscitation including isovolemic hemodilution with dextran 60, venovenouse hemofiltration, early enteral nutrition and antibiotic prophylaxis are of extreme importance. Surgery is indicated in SP with evidence of the RF when clinical course deteriorates despite intensive care, especially if infection is present and/or AACS develops. CONCLUSION: RF in the patients with SP reflects the severity of SIRS. Improvement of the visceral perfusion is the goal of resuscitation. Surgery is indicated in case of failed conservative treatment and may be successfully combined with hemodialysis. PMID- 11202288 TI - Chronic pancreatitis--biochemical, morphological, diagnostic and surgical aspects. Quality of life after surgery. PMID- 11202289 TI - Pathogenesis of endotoxemia and multiple organ failure in case of mechanical jaundice and their aggravation after the relief of cholestasis. AB - PURPOSE: To clarify the mechanisms of systemic endotoxemia in extrahepatic cholestasis and the pathogenesis of aggravation of multiorgan failure after external biliary drainage (EBD)--for elaborating of the curative tactics. MATERIALS AND METHODS: The results of experimental studies performed on 208 Wistar rats and 90 dogs were implemented in the surgical clinic in treatment of 150 patients with cholestasis. In experiments--Histological, Transmission and Scanning Electron Microscopic, and Biochemical (Malonic Dialdehide--the end product of Peroxide Oxidation of Lipids of cell membrane) methods have been used. Perfect model of EBD in cholestasis was created. In clinic--the measurement of Mitochondrial ferments, Bilirubin concentration, Creatinin clearance and Psychometric tests were used for evaluation of liver, kidney and brain functions. RESULTS: Destruction of 7.2% and 8.1% of villi in 6 and 7 days cholestasis and 17.3% and 23.5% of villi consequently in 12-14 days cholestasis (compared with 1.1%-1.4% in control [P < 0.01]) resulted in denudation of lacteals was observed. Malonic Dialdehide concentration is significantly increased in plasma after EBD in cholestasis, especially under rapid decreasing of biliary pressure. CONCLUSION: Gut barrier failure in cholestasis "lets" gram-negative bacteria and their endotoxins to penetrate the systemic circulation via the lymphatic system avoiding the liver filter. This process, which is partially suppressed by bile salts existed in lymph due to bilio-lymphatic reflux, precipices just after EBD with all consequences. Aggravation of hepatic failure after one-stage rapid biliary decompression is also promoted by activation of Peroxide Oxidation of Lipids (caused by blood reflow into portal system under falling the pressure in bile compartment) injuring the liver cells. Administration of "Duphalac" ("Solvey Pharmaceuticals")--with antiendotoxic, and "Plapheron LB" (Georgian Industry)- with anti-free-radicals properties is suggested in cholestasis not only before the operation, but after the biliary drainage as well. PMID- 11202290 TI - Risk of synchronous and metachronous liver resection for colorectal cancer metastases. AB - There is a discussion if the synchronous large bowel and liver metastatic lesions should be operated at the same time. It is the reason why we tried to find the answer based of our material. We analysed 331 liver resections due to metastatic lesions on the liver. In 61 cases (18.4%) the metastatic tumors were synchronous with large bowel tumors. The synchronic liver resections and large bowel resections were performed in 26 patient's (7.8%) and metachronic resection in 305 cases (92.2%). The policy of our Department is to perform liver resection before large bowel resection in synchronic tumors. The morbidity in the whole material was 19.0%, and mortality 3.3%. The complications ratio in synchronous liver resection was 23.1% and 17.9% in metachronic liver resection. The mortality was 3.9% in synchronous and 3.3% in metachronous liver resection. We concluded that the difference between complications and mortality in synchronous and metachronous liver resection was very little. That means that there is no risk of synchronous liver and large bowel resection. PMID- 11202291 TI - Portal hypertension--problems and dilemmas. PMID- 11202292 TI - Surgical treatment of severe necrotizing pancreatitis by the method of "open abdomen"--early and long-term results. AB - The aim of our study was the evaluation of "open abdomen" method (OAM) in treatment of severe acute pancreatitis. Fifty patients were treated by this technique in our Department from 1983 to 1999 year. Patients were retrospectively classified into 3 groups: with sterile pancreatic necrosis (SPN), pancreatic abscess(PA) and infected pancreatic necrosis(IPN). Early results embraced: number of local and general complications and a lot of parameters, which let to recognise objectively efficiency of management(time of hospital and intensive care unit stay, time of total parenteral nutrition, number of reoperations and others). These results were compared with analogical groups, in which used other management. Long-term results embraced the pancreatic efficiency tests in 24 patients in period 2-16 years after surgical treatment of OAM. Based on these results three groups of patients were separated: 12 persons (50%) recognised healthy, 4 (17%) with exocrine insufficiency of pancreas and 8 (33%) with exocrine and endocrine insufficiency of pancreas. Our results prove that OAM is the efficient treatment of IPN, but it shouldn't be used in cases of PA or SPN. Patients after OAM need prospective monitoring of exocrine and endocrine pancreatic function due to serious risk of this organ dysfunction. PMID- 11202293 TI - Surgical and endoscopic treatment of pancreatic pseudocysts. AB - Not long ago surgery was the only way to treat pancreatic pseudocysts that would not resolve spontaneously. Nowadays minimally invasive methods are gaining popularity, such as percutaneous drainage, endoscopic cystogastrostomy or cystoduodenostomy, and endoscopic transpapillary drainage. The aim of this study was to evaluate these methods in comparison with conventional surgery for pancreatic pseudocysts. From March 1997 to July 2000 we treated at the 2nd Dep. of Surgery, Wroclaw Medical University, 52 patients with pancreatic pseudocysts. 30 patients were treated surgically, 15 endoscopically, and 7 medically. For endoscopic treatment we chose patients with "mature" pseudocysts, with a distinct capsule on ultrasonography, adherent to the posterior wall of the stomach, clinically sterile, at least 5-15 cms in diameter. The endoscopic criterion was the appearance of the cyst bulging into the stomach. Surgical treatment was applicable for those patients who had no positive evidence of a direct contact of the pseudocyst and the stomach, those with cysts infected, multiple or filled with dense fluid. The observed complications (infection of the cyst and bleeding) are typically reported for the treatment of pancreatic pseudocysts. The single complication in the form of an inflammatory tumor of the pancreas was probably due to undiagnosed pancreatic necrosis. There was zero mortality in our group. In our opinion endoscopic cystogastrostomy with a double pigtail stent is a valuable alternative to conventional surgery and in selected cases can be the method of choice for the treatment of pancreatic pseudocysts. Conventional surgical methods of treatment still remain valid. They are often less hazardous as they allow full visual evaluation of the cyst and its neighbourhood (for the signs of necrosis). Surgical drainage provides secure anastomosis of the cyst with the GI tract and hemostasis, which may be vital in some cases. PMID- 11202294 TI - Endoscopy in bile ducts surgery. PMID- 11202295 TI - Inflammatory aneurysms of the abdominal aorta. PMID- 11202296 TI - Sutureless intraluminal graft for repair of high abdominal aortic aneurysm. AB - The aim of our study was experimental and clinical assessment of bifurcated grafts with ring on its main branch made of the same polyester as the prosthesis. This type of prosthesis facilitates quick anastomosis with the aorta through tying the aortic wall on the ring using a polyester tape. Experimental studies carried out on 18 pigs demonstrated good healing up of such a graft. The prosthesis was used for surgery in 8 patients with abdominal aneurysm which required clamping the aorta above renal arteries. The prosthesis was found to facilitate and accelerate making the proximal anastomosis, diminish the amount of blood loss, and reduces the time of the surgery, especially the time necessary for clamping the aorta above renal arteries which prevents renal ischaemia. PMID- 11202297 TI - Technique of transcervical--subxiphoid-vats "maximal" thymectomy in treatment of myasthenia gravis. AB - Operative technique of transcervical-subxiphoid-VATS thymectomy is described. Total sternotomy is avoided which makes the procedure less invasive without compromising its radicality. The operation is performed with aid of special device with two sternal retractors elevating the sternum from above and below and facilitating access to the mediastinum. The mediastinal pleura is incised bilaterally and exenteration of the mediastinal fat is done under control of video camera inserted through the thoracoscopic ports. Two team approach is proposed: one team, called "the cervical" team performs dissection of the neck and the superior mediastinum; the "subxiphoid" team removes the fat tissue of the anterior mediastinum. This approach makes possible reduction of the operative time to 1.5-2 h. No complications were noted in the group of 8 patients operated on by the moment of submission of the abstract. PMID- 11202298 TI - Surgery of rectal tumors. AB - The results of surgical treatment of carcinoma of the rectum have been improved in the last decades, because of the availability of stapling device, the increasing use of adjuvant or neoadjuvant treatment and the development of endoluminal surgery. Herein we present our thirty years experience in the treatment of rectal carcinoma. It deals with 690 patients operated on, 602 with conventional surgery (87%) and 88 with local excision (13%). As regards the first subgroup, in 63 patients (10.4%) the operation was considered palliative, because there were either hepatic metastases or residual tumor; 21% of the whole number had tumor in the upper third, 40% in the middle third and 39% in the lower third. Radical resection was performed in 538 patients (89.6%); 53% of the patients underwent anterior resection and 47% underwent abdomino-perineal resection. Ninety percent of tumors located in the lower rectum were managed with abdomino perineal resection and 97% of tumors located in the upper rectum were managed with anterior resection. Tumor of the middle rectum were treated indifferently with anterior resection or abdomino-perineal resection. Mortality was 4%; the morbidity was 33%. No statistical difference was found between anterior resection and Miles operation. Mean follow up is 6.8 years. Local recurrence was observed in 17% of patients and was more frequent after Miles operation than after anterior resection. The 5- and 10-year survival is respectively 53% and 43%; according to staging, 5-year survival is 68% for stage I, 64% for stage II, 39% for stage III and 9% for stage IV (p < 0.0001). As regard local excision, lesions usually arised from lower or middle rectum and were less than 3 cm. in the maximum diameter. Sixty per cent of patients received adjuvant or neoadjuvant treatment; we observed complete response with disappearance of the tumor in 28% of T2 patients. The toxicity was low: 3% of patients developed erithema and 21% different grades of proctitis. Mean duration of operation was 179 +/- 98 min' and hospitalization was less than 7 days in most of the patients. No mortality was recorded, while morbidity was 16% (14 patients). On pathological examination we observed 10 Tis (11%), 32 T1 (36%)28 T2 (32%) and 18 T3 (21%). Mean follow up is 3.3 years; local recurrence was related to staging and was respectively 0%, 16%, 25% and 61% (p = 0.0008). We did not observe local recurrence whenever T2 patients had neoadjuvant treatment and negative margins at i.o. pathological examination. Our findings show that anterior resection represents the most appropriate treatment for tumors of the upper and middle rectum; Miles operation should be reserved to tumors located within 5 cm. from the anal verge. Small tumors, confined to the rectal wall, can be properly treated with local excision; local treatment should be always associated to preoperative chemoradiation in tumors involving the muscular layer of the rectal wall. PMID- 11202299 TI - The rectal cancer with pre-operative radiotherapy--personal experience. PMID- 11202300 TI - Functional results of reconstruction after subtotal or total gastrectomy. AB - The aim of surgical treatment of gastric cancer must be complete removal of the tumor including systematic lymphadenectomy. The performance of R0-resection has to take into consideration tumor site as well as the histomorphological type described by Lauren. Therefore, subtotal distal- or total gastrectomy are complementary operative procedures nowadays. From the oncological point of view proximal gastrectomy might be indicated in some situation but increased postoperative morbidity including severe reflux-esophagitis can be obtained. According to the functional outcome subtotal distal gastrectomy should be preferred whenever justified oncologically in comparison to total gastrectomy. Among the different reconstructive methods after total gastrectomy the Roux-en-Y technique is one of the most common procedure performed. Furthermore, some patients can benefit from a reconstruction of a gastric substitute and maintenance of duodenal passage but the superiority of this technique must be evaluated in further prospective studies. The question of the optimal mode of reconstruction of the upper gastrointestinal tract is still open. PMID- 11202301 TI - Local excision of rectal cancer by transanal endoscopic microsurgery (TEM) combined with radiotherapy: new concept of therapeutic approach. AB - Transanal endoscopic microsurgery (TEM), associated with preoperative radiotherapy in selected groups, allows minimally invasive full thickness local excision of rectal tumors with perirectal fat dissection. In our experience, 95 patients with extraperitoneal rectal carcinoma underwent TEM resection for T1 (21 cases), T2 (48 cases) and T3 (15 cases) lesions. In eleven patients the pathologist did not find cancer cells in the specimen (pT0) after full dose of radiotherapy and TEM. The postoperative results were as follows: 11 minor complications (11.6%), 7 leaking sutures, 3 stool incontinence and 1 rectal haemorrhage, that resolved with medical therapy and two major complications (2.1%), one rectovaginal fistula that required reoperation and one rectourethral fistula treated by conservative therapy. No perioperative mortality was observed. Mean follow up was 40 months (range 2-96 months) with 7 (7.4%) local recurrences. Of those, 5 patients were successfully retreated and 2 high risk patients underwent postoperative radiotherapy. The overall survival in T0 and T1 patients was 100%. The overall survival in T2 and T3 patients was 81% and 62.1% respectively. This study reports the application of TEM combined with radiotherapy in the treatment of rectal cancer in selected patients. This approach is feasible, safe, and appears to be effective at the present follow up, with preservation of normal sphincter function. PMID- 11202302 TI - Is follow-up of colorectal cancer cost-effective? PMID- 11202303 TI - Diagnosis and management of colorectal obstruction. AB - INTRODUCTION: Intestinal obstruction very often results in a patient's death. The reasons of high mortality are: 1) surgeons don't follow "golden rule", which presumes performing of operations within 2 hours after diagnosis is determined, 2) delayed management, 3) the absence of reliable criteria, that can prove the definitive diagnosis, 4) difficulties in diagnosis. METHODS: The are basic rules of the modern doctrine of surgical treatment. 1. The early diagnosis. 2. The adequate preoperative preparation. 3. The early operative intervention. 4. Individual approach to the appropriate operative management and type of operation. 5. Active tactics in postoperative management. A large bowel obstraction is an emergency condition that normally requires early identification and surgical intervention. CONCLUSION: Ways of improving the results of management large bowel obstruction secondary to neoplasm are the following: 1) improving preparation of the intestine to the operation, 2) rational antibacterial therapy, 3) expansion of indications to the surgical treatment of tumors irrespective of the stage of disease. Methods of extra and intracorporal detoxication are usually used for treatment of endotoxicosis. Active treatment and diagnostic tactics in coordination with the described program provides a possibility of improving the results of treatment in this category of patients. PMID- 11202304 TI - Neuromodulation of vago-vagal reflex. AB - Functional gastrointestinal disorders are poorly understood. The lack of clear classification and definition of these disturbances interferes with unsatisfying treatment. The possible explanation has been recently looked up in the changes of brain-gut axis interactions. Simultaneously microelectronics has been made tremendous progress in the cooperation with medical sciences lately. Electronic microcircuits have become widely used in neurosciences because of their many advantages compared to standard investigational devices. Implantable microchips facilitate studies of nervous system allowing carrying on chronic experiments with minimal damage to surrounding organs. Neuromodulation of autonomic nerves gives promise for treatment refractory disturbances of gut motility. PMID- 11202305 TI - Tailoring antireflux surgery: where do we stand? A critical review of the literature. PMID- 11202306 TI - Barrett's surgery in 2000. PMID- 11202307 TI - Gastrointestinal motility in surgical clinic. PMID- 11202308 TI - Esophageal motility impairment--the cause or consequence of gastroesophageal reflux disease? AB - There are at least three, well-known, different groups of motor activity disturbances of the upper part of alimentary tract which can induce the development of gastroesophageal reflux disease (GERD) and enlarge the risk of excessive exposure of the esophageal mucous membrane on gastric juice and/or biliary contents. Most important is insufficiency of the lower esophageal sphincter (LES), which causes gastroesophageal reflux at 50-60% of patients suffering from GERD. Other reasons include impairment of stomach function (increase of intra-gastric pressure, late emptying and/or hypersecretion), and impairment of esophageal clearance. The question: does motility impairment of the esophagus occur primary or secondary to the gastroesophageal reflux, is still not enough clarified. Motor activity of the esophagus before and after the antireflux operation was prospectively assessed in 57 patients. Motility of the esophagus was determined by estimation: the efficacy of LES, general motor activity of the body of the esophagus and motor activity of the body during the reflux episodes, basing on 24-h manometry. Comparison of general pre- and postoperative data revealed significantly positive influence of Nissen-Rossetti fundoplication on improvement of motor activity of the esophagus, but the results differed in relation to the height of the measurements. Moreover comparison of the data during gastroesophageal reflux episodes revealed negative changes of the manometric parameters in the upper and middle esophagus. We conclude that post operative improvement of esophageal motility confirms the secondary dysfunction in the peristalsis, connected with pathological reflux. However, lack of the complete normalization in motor activity after operation suggests that disorder may partially occur as primary impairment of motor activity or as the secondary dysfunction, which is fixed in the course of GERD. PMID- 11202310 TI - An old and a new challenge in endocrine surgery: management of substernal goitre & endoscopic removal of adrenal tumors. PMID- 11202309 TI - The relationship between improved prognosis in gastric cancer patients in the last 25 years and changing methods of surgical and combined treatment. AB - BACKGROUND: Poland is among the countries with the high morbidity and mortality rates for gastric carcinoma (GC). The differences of GC biology depending on the geographical regions were suggested. In the literature, there are no reports from detailed clinicopathologic studies carried out in large series of GC patients in Poland. METHODS: Based on the prospectively collected data of 3696 GC patient treated surgically between 1977-1999, potentially significant prognostic factors were analyzed to assess their prognostic value, and their time related distribution during the over 20-year period of the study. RESULTS: The mean age of the patients was 59.0 (SD 11.6) years and ranged from 20 to 93 years. The male to-female ratio was 2.3. Overall cumulative 5-year survival was 0.28 (for early GC 0.85) and significantly increased over the period of study. Among factors analyzed the depth of invasion, lymph nodes status, tumor size, age, UICC-R classification and rate of involved to removed lymph nodes are of statistically significant and most important prognostic value. In the over 20-year period of study the rate of diffuse type carcinoma acc. to Lauren increased but the tumor locations did not changed significantly. The rate of early GC did not change throughout the period of study but number of most advanced cases decreased. Chemo and chemotherapy improved outcomes in some groups of patients. CONCLUSIONS: The basic clinicopathologic profile of Polish patients is similar to the reported in Western Europe and Japan, except for significantly higher early GC occurrence in Japan. According to the obtained results the prognosis of GC depends clearly upon the stage of the disease at the time of surgery. The improvement of outcomes during over 20 years of GC study in Poland was due to introducing better diagnosis and routine multimodal treatment. PMID- 11202311 TI - Surgical treatment of carcinoid tumours. AB - Carcinoid tumours are the most common endocrine tumour of the gut comprising 75% of appendicular tumours and a third of ileal tumours. They are also an incidental finding in 1% of post mortems. Carcinoid syndrome however is rare and it is estimated that two cases would appear in a quarter of a million population over a decade. We have reviewed a consecutive series of carcinoid tumours accrued from 1976-1999 in order to further study the natural history of the disease and also to examine the relationship between pathological tumour size, extent of disease and prognosis for each tumour site. In this 19 year period 145 patients were treated for the disorder. The bronchus was the commonest site (35.9%) with appendix (24.8%) and ileal (13.8%) carcinoids comprising the majority of known primaries. Overall midgut carcinoids comprised 40.7% of the series with the carcinoid syndrome present in 20.3%. A significant group was constituted by those patients presenting with metastatic disease and an uncertain site of primary tumour (9.7%). Metastatic disease was not found on presentation or follow up in any patient with a foregut primary tumour less than 2 cm diameter or a midgut primary tumour less than 1 cm diameter; a direct correlation of size and metastases being found above these levels. Overall survival for all groups was 60% at 5 years with the best prognosis being seen in patients with bronchial or appendicular carcinoids. Other clinical features, pathology, extent of disease and prognosis of carcinoid tumour will be discussed along with the role of current management strategies. PMID- 11202312 TI - Unusual pancreatic tumours. PMID- 11202313 TI - European Society of Surgery 4th Annual Meeting. Krakow, December 3-6, 2000. Abstracts. PMID- 11202314 TI - Transesophageal echocardiography during cardioversion of atrial fibrillation. PMID- 11202315 TI - Scalar versus vector electrocardiography to determine right coronary artery or left circumflex coronary artery occlusion in inferior wall acute myocardial infarction. PMID- 11202316 TI - Electrocardiographic lead reversal. PMID- 11202317 TI - ABCs of thrombolysis. PMID- 11202318 TI - Comparative examination of the accuracy of a mechanical and an optical system in CT and MRT based instrument navigation. AB - The aim of an intraoperative instrument navigation system is to support the surgeon in the localization of anatomical regions and to guide the use of surgical instruments. An overview of technical principles and literature reports on various navigation systems is provided here. The navigation accuracy (tested on a plastic phantom under simulated operating room conditions) of the mechanical Viewing Wand system and the optical SPOCS system amounts to 1 to 3 mm for computerized tomography (CT) data, with a significant inverse dependence on the layer thickness. The values for magnetic resonance tomography (MRT) data are significantly higher. In regard to the choice of registration points, a statistically inverse dependence exists between the number of points and the distance between the points. During the time period between autumn 1993 and mid 1999, more than 120 clinical applications were performed. The intraoperative accuracy was in the range of < or = 3 mm. Registering the patient position with preoperatively inserted screw markers achieved accuracy values of < or = 2 mm. The instrument navigation technique has proved to be very advantageous for the spatial orientation of the surgeons. The possibility of checking resection borders has opened up new perspectives in tumor surgery. A quality improvement and a reduction of the operational risks as well as a considerable decline in the stress placed on the patient can be expected in the near future due the techniques of computer-assisted surgery. PMID- 11202319 TI - Extra-articular pigmented villonodular synovitis of the temporomandibular joint: case report and review of the literature. AB - Pigmented villonodular synovitis (PVNS) is a benign proliferative disorder of the synovial tissue, that usually affects the knee, ankle and other major joints. Involvement of the temporomandibular joint is, however, very rare. We describe a new case of recurrent PVNS arising from the temporomandibular joint that was classified as diffuse extra-articular type and was successfully treated surgically. The etiology and clinical features of PVNS are discussed and the previously reported cases in the literature are reviewed. PMID- 11202320 TI - Vertical distraction of the severely resorbed mandible. The Groningen distraction device. AB - In this paper, both the surgical procedure and the clinical results of a novel distraction device to augment a severely resorbed anterior edentulous mandible are described. The distraction device is non-voluminous, and consists of two distraction screws and one guide screw. Two months after the last day of distraction, both distraction screws are replaced by endosseous implants and the guide screw is removed. Three months after implantation, the prosthetic treatment can be started. So far three patients have been treated. In all patients, the severely resorbed mandible (mandibular height in the canine region: 5, 6 and 7 mm, respectively) could be sufficiently enlarged to enable reliable insertion of endosseous implants with a length of at least 12 mm. No complications occurred. Biopsies taken from the distraction site revealed formation of lamellar bone parallel to the distraction vector. From this preliminary study it is concluded that the Groningen vertical distraction device has the potential for reliable augmentation of the anterior segment of a severely resorbed edentulous mandible to enable insertion of endosseous implants with adequate length and primary stability. PMID- 11202321 TI - Recovery of mandibular motion after closed and open treatment of unilateral mandibular condylar process fractures. AB - The purpose of this study was to determine the rate of recovery of mandibular motion in patients treated for fractures of the mandibular condylar process. One hundred and thirty-six patients (111 men, 25 women), 74 treated by closed and 62 by open methods, were included. They underwent testing of mandibular and condyle mobility at 6 weeks, 6 months, and 1, 2, and 3 years post surgery. Their ranges of motion were compared to those of 52 controls (26 men and 26 women). A jaw tracking device was used to assess mandibular motion. Multilevel statistical models were used to assess differences between groups, and to estimate rate of recovery in the fracture patients. In general, patients with unilateral fractures of the condylar process had maximum excursions that returned to normal values within 3 years after fracture, regardless of treatment. Patients treated open exhibited a faster rate of improvement in maximum interincisal opening than patients treated closed (0.43 mm/month vs 0.15 mm/month, respectively), but part of the difference was due to a significantly smaller opening after 6 weeks for the patients treated open (38 mm vs 42 mm, respectively). Patients treated open also exhibited a faster rate of improvement in maximum excursion toward the fracture side than patients treated closed (0.10 mm/month vs 0.04 mm/month, respectively). Based upon this study, patients with unilateral fractures of the condylar process, who are treated closed and not put into maxillomandibular fixation but are instructed in physical therapy, can be expected to achieve normal maximum excursions within 3 years after treatment. Patients treated open will have reduced maximum opening initially, but may reach normal levels of opening sooner than patients treated without surgery. Patients treated without surgery may have smaller than normal excursion toward the non-fracture side for at least 3 years after fracture, especially if their fracture was at or above the condylar neck. Improvement rates for other maximum excursions are similar for patients treated with or without surgery. PMID- 11202322 TI - Intraorbital bamboo foreign body in a chronic stage: case report. AB - A case of intra-orbital bamboo foreign body in a chronic stage is presented. This case seems to confirm the importance of radiological examination, including three dimensional computed tomography to choose the optimal surgical approach to remove the foreign body. PMID- 11202323 TI - Management of refractory osteoradionecrosis of the jaws with surgery and adjunctive hyperbaric oxygen therapy. AB - This retrospective study aimed to determine the effectiveness of surgery and hyperbaric oxygen (HBO) treatment in the management of refractory osteoradionecrosis (ORN) of the jaws. Of the 18 patients who had undergone this treatment, 14 patients had complete healing, 3 patients had improved and one patient did not show any improvement. Of the 14 patients who had complete healing, only 4 still had a discontinuity defect of the mandible but they declined additional reconstructive surgery. In conclusion, surgery/HBO therapy showed satisfactory results in the management of refractory ORN of the jaws. PMID- 11202324 TI - Hyperbaric oxygen in the therapeutic management of osteoradionecrosis of the facial bones. AB - This paper reviews all 17 cases of facial bone osteoradionecrosis (ORN) which were treated in Adelaide, South Australia, in a nine-year period (1987 1996). This was 1.2% of all cases of head and neck cancer treated with radiotherapy (RT). Fourteen cases received treatment following the Marx principles of staging and the protocols of hyperbaric oxygen plus or minus surgery. The three exclusions were two patients who died of recurrent cancer before treatment was complete and one who declined treatment. The eleven cases of mandibular ORN occurred within a few years of the initial RT treatment. All except one occurred after surgical trauma, with dental extractions being the factor in nine cases. All responded to HBO, with or without surgery depending on stage. The three cases of temporal bone ORN were all of late spontaneous onset. All were stage I and all responded to HBO alone. This study shows that the incidence of ORN in Adelaide is low, probably through use of conservative doses of RT and good preventative protocols. The treatment with HBO plus or minus surgery was effective. PMID- 11202325 TI - Pyknodysostosis--a report of two cases with a brief review of the literature. AB - Pyknodysostosis is a rare sclerosing bone disorder that has an autosomal dominant trait. It is characterized by short stature, brachycephaly, short and stubby fingers, open cranial sutures and fontanelle, and diffuse osteosclerosis, where multiple fractures of long bones and osteomyelitis of the jaw are frequent complications. We present a report of two cases of pyknodysostosis with evidence of long bone fractures and chronic suppurative osteomyelitis of the jaws in one of the cases. Some of the specific oral and radiological findings that are consistent with pyknodysostosis are reported, along with a brief review of the literature. PMID- 11202326 TI - Multiple odontomas in the facial bones. A case report. AB - A rare case of multiple compound odontoma involving the facial bones and erupting into the oral cavity of a 15-year-old Nigerian girl is presented. The unacceptable facial appearance and the surgical approach used makes this case worth reporting. PMID- 11202327 TI - Chondroid lipoma: a rare but diagnostically important lesion. AB - Chondroid lipoma is a rare benign fatty tumour that has been confused with liposarcoma and chondrosarcoma. We present a case in a 44-year-old man and highlight the features that differentiate this benign lesion from the more aggressive ones. PMID- 11202328 TI - Highly aggressive brown tumour of the maxilla as first manifestation of primary hyperparathyroidism. AB - A case is presented of a 62-year-old man with a right maxillary swelling for the previous three months. The lesion was expansive and osteolytic, with invasion of the adjacent maxillary sinus, nasal and pterygomaxillary fossae and floor of the orbit. Histology revealed the presence of an intrabony giant cell lesion. Blood tests demonstrated elevations in calcium (16.2 mg/dl) and parathyroid hormone (PTH) concentrations (841 pg/ml). This suggested the diagnosis of hyperparathyroidism initially manifesting as a brown tumour of the maxilla. Posterior explorations confirmed the existence of an underlying ectopic parathyroid adenoma as the cause of the condition. PMID- 11202329 TI - Salivary gland involvement as an initial presentation of Wegener's disease. A case report. AB - The case is presented of a 47-year-old woman with an 8-week history of persistent right ear discomfort and a 2-week history of unilateral parotid swelling, as well as peripheral paresis of the facial nerve. The case points to the difficulties encountered when Wegener's granulomatosis presents in an unusual and varied way which mimics a malignant tumour of the parotid gland. To our knowledge, the association of parotid gland involvement and facial palsy in Wegener's granulomatosis has not previously been described in the literature. PMID- 11202330 TI - Optical biopsy systems for the diagnosis and monitoring of superficial cancer and precancer. AB - Histopathology is the gold standard in the diagnosis of cancer and dysplasia. Screening for the disease in high-risk populations(6,15) and choosing the correct site for biopsy have implications for the choice of follow-up intervals and therapy. Sully & Field(12) suggest that molecular genetic analysis, such as the polymerase chain reaction, for detecting progressive loss of heterozygosity, may be a more accurate predictor of the clinical course of oral cancer. This technique is now semi-automated and compares favourably with the time taken for histopathology (commonly 1-2 weeks). Recent developments suggest that the fluorescent and spectroscopic features may distinguish diseased from healthy tissue, and below follows an introduction for the clinician to this fascinating and complex field. It is possible to obtain a diagnosis in real-time and, with the appropriate use of photochemicals and image enhancement, it may be possible to treat and monitor the effects of treatment in real-time. PMID- 11202331 TI - [Effectiveness coefficient for laryngographic closure of the glottis as a way of evaluating airway protection against aspiration of gastric contents]. AB - Laryngographic examination was conducted on 35 men aged 45 to 65 with good hearing and proper pronunciation. Based on the examination, the proposed by the authors of this paper laryngographic closure effectiveness coefficient of the glottis (LCEC) was calculated as a way for evaluating protection of airways against the aspiration of food. Glottis occlusion serves an essential function as a mechanism protecting airways, especially in patients who have undergone horizontal supraglottic laryngectomy. The examination was conducted with the purpose of obtaining numerical values of LCEC, which will be treated as results of the controlled group during the examination of swallowing disorders in patients with partial laryngectomy. PMID- 11202332 TI - [Classification of rhinosinusitis]. AB - Rhinosinusitis is a multifactorial disease which has been variously defined by far. There is a strong need among all physicians to create a commonly accepted classification of rhinosinusitis, providing indications for an appropriate evaluation, diagnosis and treatment of the disease. The goal of this review is to present leading definitions of different forms of rhinosinusitis as well as classifications based on clinical findings, temporal considerations and the patophysiology of rhinosinusitis. PMID- 11202333 TI - [Use of argon coagulation in laryngology--personal experience]. AB - In order to remove or destroy pathological changes of mucosa or control of bleeding in upper respiratory tract or in upper part of alimentary tract there are used various surgical technics including: electrocoaggulation, cryotherapy, laser-therapy. Argon plasma coagulation (APC) makes a new operative technique which is based on physical phenomenon of high frequency electric current flow through ionized argon plasma. There are several advantages of APC i.e.: no contact between applicator and tissue, no carbonization effect, possibility to control the application, large surface treatment. Authors present their own research in APC usage at 42 patients (age average 38.2, women 16, men 26). Estimating preliminary results of treatment APC can be described as an advantageous treatment method of nasal concha hypertrophy, nose bleeding (including Osler disease), nasal cavity polyps and pappilomas removal. PMID- 11202334 TI - [Evaluation of airway protection against aspiration of gastric contents in patients after partial laryngectomy using the laryngographic closure effectiveness coefficient of the glottis/neoglottis]. AB - Laryngographic examinations were conducted on 97 patients who had undergone partial laryngectomy and on 35 subjects being a control group. The study of effectiveness of glottis or neoglottis performed with the use of laryngograph showed no relation between glottis/neoglottis occlusion effectiveness index and intensified swallowing disorders. This shows the lack of compensating option in swallowing disorders with the help of a mechanism based on an efficient glottis or neoglottis occlusion alone. PMID- 11202335 TI - [Ultrasonographic intraoperative evaluation of neoplastic changes in the tongue, tonsil, larynx, salivary and neck masses--preliminary report]. AB - The new diagnostic method, intraoperative ultrasound is presented. There are very few publications in the literature, but they mainly concern the application of transcutaneous ultrasound in localizing the abscesses, their puncture and drainage. Intraoperative imaging of tongue, tonsil, larynx tumors, submandibular and parotid glands and neck masses have been provided by means of a linear 7.5 MHz probe in Poznan ENT Dept. K. Marcinkowski University of Medical Sciences. The application of this method is pioneer and new. The aim of the study was to compare the sensitivity and the specificity of preoperative, transcutaneous ultrasound with the intraoperative one, to assess how the new method influences the extensiveness of the performed procedures and sonographic-surgical correlation of safety margins. MATERIAL: 5 patients with parotid tumors, 4 with tongue, 6 with tonsil and 6 with larynx cancers have been examined. In 13 of them, apart from primary site diagnostics, the neck masses have been assessed. The imaging documentation is presented and the preliminary conclusions concerning the usefulness of this method have been drown. PMID- 11202336 TI - [Androgens and laryngeal cancer]. AB - The article concerns relations between larynx cancer and androgenic activity in men. Up till now the role of androgens in laryngeal carcinogenesis has not been established. Authors point out to andropenia (gonadal and supracortical) in elderly males and its influence on larynx cancer occurrence in the course of aging. Results of androgen receptor studies in unchanged and neoplastic tissue of the vocal organ are described. There is presented data on serum androgen concentrations in healthy men and patients with laryngeal neoplasms. The necessity of further studies of the larynx cancer's hormone-dependence is underlined. PMID- 11202337 TI - [Clinical significance of cytogenetic examinations in squamous cell carcinomas of the head and neck]. AB - The karyotypes of head and neck cancer usually display complex chromosomal aberrations. There is no specific aberration in this type of cancer, although the rearrangement of chromosome 11 involving the band 11q13, often with its amplification, seems to be significant. Unfavourable prognostic factors are complex karyotype, aneuploidal DNA content and the rearrangement or amplification of 11q13 and are associated with shorter survival. Diploid DNA content is prognostically favourable in this type of neoplasm. PMID- 11202338 TI - [Functional coordination of upper airway ciliated cells]. AB - Generation mechanism of the "calcium wave" in ciliated cells is presented. Influence of this phenomenon on ciliary activity is pointed out. PMID- 11202339 TI - [The vestibular system and migraine in children]. AB - Migraine in childhood is relatively common disease. Although clinical practice and scientific publications recognize frequent association of migraine and vestibular disorders, relationships have yet to be well defined. In present study the vestibular function was extensively tested in 20 children suffering from migraine. All the patients underwent complete neurootological examination including tonal threshold audiometry, testing of vestibulo-spinal reflexes- Romberg and Unterberger-Fukuda tests, Dix-Halpike test for BPPV, videonystagmography. On videonystagmography each patient was evaluated regarding: calibration, spontaneous nystagmus, gaze nystagmus, eye tracking test, optokinetic and positional nystagmus, and caloric testing. The same procedure have been performed regarding control group comprised of 15 healthy. All the patients with migraine presented abnormalities in vestibular testing. Analysis of the results showed that: functional state of structures forming both visuo-ocular and vestibulo-ocular structures was altered in all the migraine patients evaluated in the study, pathological findings suggest mainly central localisation of vestibular dysfunction in children suffering from migraine, the number of pathological VNG findings seems not to be correlated with the type of migraine. PMID- 11202340 TI - [Bacteriologic evaluation of middle ear fluid during the course of secretory otitis media in children]. AB - Fluid collected from tympanic cavity during operation from 43 children with O.M.S. was subjected to bacteriological examination. After the collection, each sample was immediately applied to Bactec Peds Plus/F liquid medium from Becton Dickinson. The number of samples, where each genus and species of bacteria were found, was determined, as well as the number of samples where every two genus coexisted; also the pH genes, in which each genus was found were calculated. Obtained results showed that 22 species of bacteria, belonging to 6 genus lived in the samples. The most commonly occurring genus were Staphylococcus, Streptococcus and Haemophilus; the most rare genus were Moraxella and Bacillus. The most common species were: Haemophilus influenzae (18.6% of samples), Staphylococcus aureus (14.0%), Staphylococcus epidermidis (11.6%), Staphylococcus warneri (9.3%) and Streptococcus oralis (7.0%). Streptococcus coexisted most frequently with Staphylococcus and Haemophilus; Staphylococcus--with Haemophilus and Bacillus; Haemophilus--with Streptococcus and Staphylococcus. The pH ranges for the three most often found genus were: for Staphylococcus--7.7-9, for Streptococcus--7.7-9.3 and for Haemophilus--8.2-8.8. PMID- 11202341 TI - [Cytologic nasal smears in patients with mucoviscidosis]. AB - 58 cytological smears taken from the surface of the nasal mucosa of patients with mucoviscidosis were analysed. In 69% of the smears prevalence of pseudostratified columnar epithelium was present. Squamous metaplastic changes was found in 31% of the smears. Many goblet cells were present in 19% of the smears. PMID- 11202342 TI - [Bacteriologic evaluation of otitis externa and chronic otitis media]. AB - The authors present results of bacteriological examinations in 187 patients with chronic otitis media (OMC) and otitis externa treated in ENT Department, Medical University of Gdansk in the years 1997-1998. Ear swabs and aspirates were investigated for aerobes and anaerobes 254 bacterial isolates were obtained. Among 150 patients with OMC aerobes were isolated in 130 (86.7%) in 13 (8.5%) mixed aero-anaerobes flore and in 20 (19.3%) no bacterial growth was observed. From patients with COM there were 199 bacterial isolates among them 177 aerobes cultures, 13 anaerobes and 9 fungal. From the external ear canal there were 55 cultures, among them 45 (81.8%) aerobes, 6 (10.9%) mixed aero-anerobes and 4 (7.3%) fungal. The most frequent observed bacteria were Staphylococcus aureus, Pseudomonas aeruginosa and Proteus mirabilis which showed the best susceptibility on ciprofloxacine and amikacine. PMID- 11202343 TI - [Rehabilitation of benign paroxysmal positional vertigo in the experience of the Wroclaw Clinics]. AB - Mechanical disturbances in inner ear in cupulo-utricular complex are the cause of Benign Paroxysmal Positional Vertigo (BPPV). Pharmacotherapy is ineffective in such cases. The results of rehabilitation with the use of Semont of Epley manoeuvres in 46 patients were presented. The regression of symptoms in 24 cases treated with the use of Semont manoeuvre was achieved in 62% and in 22 cases treated with the use of Epley manoeuvre in 73%. Theoretical assumptions of effectiveness of treatment applied were discussed on the basis of cupulolithiasis and canalolithiasis theories. PMID- 11202344 TI - [Congenital laryngomalacia in children]. AB - Laryngomalacia is the most common cause of congenital infantile stridor which is respiratory in all cases. It is first noted at birth and usually resolves spontaneously by the age of 2 years. In severe cases it may lead to life threatening obstructive apnea, cor pulmonale and failure to thrive, and in these patients surgical intervention may be required. This anomaly has been described in the medical literature for over 100 years. The purpose of this study is to review the literature, present terminology, types of laryngomalacia, cause, pathogenesis and relationship with other diseases. Finally, we describe the possible methods of its treatment. PMID- 11202345 TI - [Usefulness of chromosome alteration analysis in cell lines derived from laryngeal tumors for evaluation of laryngeal neoplasms]. AB - A classical cytogenetic analysis was applied to analyse karyotypes of 9 cell lines derived from laryngeal cancer. The most frequent aberration was a deletion of the whole sex chromosome Y. An abundance of somatic chromosome alterations was further analysed to find correlation with tumour staging and grading. A conventional cytogenetic analysis seems to be not sufficient to recognize chromosome alterations specific for a given tumor stage. On the other hand, an analysis in respect to histologic grading has indicated for an association between rearrangement of 9 chromosome and a high tumor aggressiveness. It seems that a combination of conventional cytogenetics with molecular methods (FISH, CGH) would be helpful in diagnosing of laryngeal cancer. PMID- 11202346 TI - [Functional hearing loss in children]. AB - The cases of children diagnosed with pseudohypacusis in the Department of Pediatric Otolaryngology were presented. Probable mechanism of its pathogenesis was described. The main stress was put on its correct diagnosis particularly in children with co-existing organic changes. Diagnosis of pseudohypacusis in children is not problematic provided that the occurence of this disease is taken into consideration during diagnostic procedures. PMID- 11202347 TI - [A case of long-term presence of a foreign body in the esophagus]. AB - The following long-term presence of foreign body in esophagus in psychotic patient. Diagnostic and treatment principles of foreign body in esophagus was discussed. PMID- 11202348 TI - [A case of maxillary neurosarcoma]. AB - A case of neurosarcoma located in maxillary sinus is presented. The patient was 62 years old women who complained of nasal obstruction, epistaxis and headache. Results of physical examination showed a giant mass filling the nasal cavity and maxillary sinus. The lesion was completely resected by lateral rhinotomy way. After the operation histopathological diagnosis was difficult, one pathologist recognised schwannoma benignum other one sarcoma. Finally postoperative diagnosis was schwannoma benignum, it was misdiagnosis. Two years later the patient was surgically treated again because of tumor recurrence. These time pathological diagnosis was neurosarcoma. Radiotherapy was done as well. The patient died 18 months after treatment, tumor regrowth and generalization metastases was reason of the death. PMID- 11202349 TI - [Osteoma of the maxillary sinus]. AB - Osteomas of paranasal sinuses occur mainly in frontal and ethmoid sinus, in maxillary or sphenoid sinus are seen very rarely. The authors present a review of literature and next describe a case of spongioid osteoma in 42-years old female. The clinical features and radiologic assessment of the disease are presented. The tumour was resected by Caldwell-Luc operation with very good long term result. PMID- 11202350 TI - [Giant osteoma of the paranasal sinuses passing into the anterior cranial fossa]. AB - A case of giant osteoma of paranasal sinus passing into anterior cranial fossa was presented. The frontal craniotomy in order to removing this tumor was applied. In any case of such tumor the CT seems to be a necessary examination. PMID- 11202351 TI - [A case of malignant parapharyngeal schwannoma in a 29-year old woman]. AB - The schwannoma malignum of parapharyngeal space is a very uncommon tumor. The case of the malignant neurilemmoma located in parapharyngeal space in 29-year-old female, is presented in the paper. The tumor was removed through the cervical parotid approach. The post-surgery, follow-up examinations and CT check-up did not reveal any traces of recurrence. PMID- 11202352 TI - [Teratoma in the middle ear and throat of an infant]. AB - The authors present a case of an 8-moth-old female infant treated for prolonged otitis media. The inflammatory process was connected with teratoma of tympanum and throat. The authors discuss presumable connection of the both masses. The child was completely cured by surgical treatment. PMID- 11202353 TI - [The case of a large orbital foreign body evacuated by lateral orbitotomy using the Kronlein-Reese-Berk method]. AB - The authors describe a case of patient with orbital large foreign body (glass) treated using Kronlein lateral orbitotomy. PMID- 11202354 TI - [Retained teeth in the maxilla]. AB - Two cases of retained teeth in maxilla, very rare disease seen in otolaryngological practice, are described. The authors present causes of this pathology, symptomatology, diagnostics and treatment. Diagnosis of retained teeth is made mainly by radiologic investigation i.e. CT and pantomography. A review of literature was made. PMID- 11202355 TI - [About the beginnings of otolaryngology in Poland in commemoration of the 150th anniversary of Teodor Heryng's birthday and the 100th anniversary of the founding of the first Laryngology Ward in Warsaw]. AB - In this study was remain biography of two pioneers of polish laryngology--Teodor Heryng and Leopold Lubliner. The first laryngological subdivision in Warsaw was localised in St. Roch hospital. The first full equipment laryngological division where was open in Jewish hospital. PMID- 11202356 TI - [Struggles with nasal septum malformations in the XIX century]. AB - The maxilla-premaxilla approach to extensive nasal septum surgery performed in 1959 by M.H. Cottle and all is a obligatory method today. The struggle with a nasal septum deformations from the half of eighteenth of XIX century is presented (S.T. Quelmaltz). The correction of nasal septum by "the compression method", usually the vain method performed by A. Jurasz sen., P.L-B. Guersant, M. Warren, E.P. Chassaignac, F. Petersen and others are described in detail. The willful nasal septum perforation was performed by P.F. Blondin and P.T. Rupprecht. The special forceps were used by A. Jurasz sen. and R. Adams. The dorsum nasal cut was performed by J.N. Demarquay and B.R. Langenbeck. The destruction of inferior nasal concha was performed by M. Mackenzie and P. Delavan. The employment of galvanokauterization and electrolysis by A. Jurasz sen., F.E. Voltolini, C. Miot and E.M. Moure is mentioned. A description of fenestrated resection of septi nasi by Krieg in 1886 and then modified by G. Killian is presented. PMID- 11202357 TI - [Training of Polish physicians in rhinolaryngology in XIX century Vienna]. AB - The eminent Viennese rhinolaryngologists in the XIX century were: Leopold Schroetter, Karl Stoerk, Johann Schnitzler, Ottokar Chiari, Markus Hajek and others. Stroerk, the pupil of Ludwig Turck was a head of rhinolaryngological clinic since 1891, he was also the author of valuable papers, among other things on rhinoscleroma. Schnitzler, the assistant of Johann R. von Oppolzer was a head of Viennese polyclinic. The therapeutical nihilism in Viennese clinics is mentioned. Ottokar Chiari, the assistant of Schroetter was an eminent rhinolaryngologist. Markus Hajek was a head of otorhinolarynoglogical clinic in Vienna performed in 1919. Theodor Billroth, professor of surgery in Vienna was the first to remove the larynx for cancer in 1873. PMID- 11202358 TI - [Studies on pathologic changes localized in the middle ear, their influence on hearing impairment and choice of surgical treatment]. PMID- 11202359 TI - Bound transcription factor suppresses photoproduct formation in the NF-kappa B promoter. AB - The relationship between purified transcription factor p50 binding and ultraviolet light-induced DNA damage formation in the NF-kappa B promoter element was investigated. The effect of bound transcription factor on cyclobutane dimer formation was quantified using Maxam-Gilbert analysis of irradiated substrate digested with T4 phage endonuclease V. Two methods were employed for cleaving (6 4) photoproducts. Sites of (6-4) photoproducts cleaved by piperidine showed a general suppression in the presence of bound p50 protein similar to that observed for cyclobutane dimers. In contrast to piperidine, digestion with ultraviolet damage endonuclease (UVDE) from Saccharomyces pombe subsequent to cyclobutane dimer reversal by photolyase displayed a broader spectrum of damaged sites. Whereas some of these sites were suppressed by bound p50 protein, some remained unaffected and one site showed increased (6-4) photoproduct induction. These data illustrate the advantage of UVDE over piperidine for studying (6-4) photoproducts at the sequence level and suggest that this approach may be useful for footprinting transcription factor binding in other promoters. PMID- 11202360 TI - Determination by fluorimetric titration of the ionization constants of ciprofloxacin in solution and in the presence of liposomes. AB - A fluorescence titration method was applied for the determination of pKa of ciprofloxacin (CPX) in solution. Values of 6.18 +/- 0.05 and 8.76 +/- 0.03 were obtained for pKa1 and pKa2, respectively. The method was used to determine the ionization constants in the presence of liposomes of dipalmitoylphosphatidylcholine (DPPC) and DPPC with 10 mol% of dipalmitoylphosphatidylglycerol. A dependence on the surface charge of liposomes was found which supported the existence of a basic electrostatic interaction between CPX and the phospholipid bilayer. Both pK values for the N-4 butyl piperazinyl derivative (BCPX) of the parent compound were also determined in solution and in the presence of liposomes. The competition of both drugs for the same binding site as 1-anilino-8-naphtalene sulfonate demonstrate that the interaction is governed by electrostatic forces. PMID- 11202361 TI - Dose response for ultraviolet radiation A-induced focal melanocytic hyperplasia and nonmelanoma skin tumors in Monodelphis domestica. AB - Four groups of 30 dorsally shaved opossums (Monodelphis domestica) were exposed to graded doses of ultraviolet radiation A (UVA) (320-400 nm) three times per week for 90 weeks. Animals were monitored for the appearance of focal melanocytic hyperplasia (FMH) and nonmelanoma skin tumors (NMST) during the course of the exposures and for an additional 20 weeks following termination of exposures. FMH is the putative precursor for melanoma in the opossum. The lowest dose of UVA (2.5 x 10(3) J/m2) used in this study was selected based on the action spectrum for the induction of melanoma in a fish model. The prediction was that 2.5 x 10(3) J/m2 would induce FMH in the opossum if the action spectra for the induction of FMH in the opossum and melanoma in the fish were the same. The highest UVA dose was 2.5 x 10(5) J/m2. Only the highest dose of UVA gave a statistically significant induction of FMH and NMST in the opossum. As in previous studies, the FMH appeared earlier than the NMST during the course of exposures and the final prevalence of FMH was lower than the final prevalence of NMST. Overall, the results of this study indicate that the efficacy of UVA to induce FMH in the opossum is not as great as would be predicted from the action spectrum for melanoma induction in a fish model. PMID- 11202362 TI - Multi-waveband solar irradiance on tree-shaded vertical and horizontal surfaces: cloud-free and partly cloudy skies. AB - Irradiance measurements of short wave (SW), photosynthetically active (PAR), ultraviolet-A (UVA) and ultraviolet-B (UVB) solar radiations were made on horizontal and vertical surfaces in the shade of trees under cloud-free and partly cloudy skies. All measurements were referenced to the irradiance of a horizontal surface above the canopy. For horizontal shaded surfaces under cloud free skies, the values of the ratio (Rh) of below- to above-canopy horizontal irradiance were similar for the UVA and UVB wavebands and for the SW and PAR wavebands. However, Rh for the UV wavebands differed from that for the PAR and SW wavebands. Overall, values of Rh in the shade typically varied as PAR < SW << UVA < UVB. The irradiance ratios for vertical surface in the shade typically varied as UVB > UVA = SW > PAR. In absolute terms, UVB irradiance (Ih) on tree-shaded horizontal surfaces increased relative to a cloud-free sky when a translucent cirroform cloud was in front of the sun, but decreased when the cloud was in a region of sky away from the sun. Translucent cirroform cloud cover also tended to decrease the UVB irradiance (Iv) for a shaded vertical surface (either facing the sun or south) relative to that under cloud-free skies, regardless of where the clouds were in the sky. In all other wavebands the shaded Ih and Iv increased under translucent cirroform cloud cover relative to cloud-free skies, regardless of where the clouds were in the sky. PMID- 11202363 TI - Fluorescence imaging and spectroscopy of ethyl nile blue A in animal models of (pre)malignancies. AB - Discrimination between normal and premalignant tissues by fluorescence imaging and/or spectroscopy may be enhanced by a tumor-localizing fluorescent drug. Ethyl Nile Blue A (EtNBA), a dye with no phototoxic activity, was investigated for this purpose. The pharmacokinetics and tissue-localizing properties were investigated in a rat palate model with chemically induced premalignant mucosal lesions (0.5 mg/kg EtNBA intravenous [i.v.]), a hairless mouse model with UVB-induced premalignant skin lesions (1 mg/kg EtNBA intraperitoneal) and in a rat skin-fold observation chamber model on the back of a rat with a transplanted solid tumor (2.5 mg/kg EtNBA i.v.). Fluorescence images and spectra were recorded in vivo (600 nm excitation, 665-900 nm detection) and in frozen tissue sections at several time points after EtNBA administration. In the rat palate the EtNBA fluorescence was maximum almost immediately after injection, whereas in the mouse skin and the observation chamber the fluorescence maximum was reached between 2 and 3 h after injection. EtNBA cleared from tissues after 8-24 h. EtNBA localizes in the transplantable solid tumor, but is not targeted specifically to the dysplastic location in the rat palate and mouse skin. However, in the rat palate the EtNBA fluorescence increased significantly with increasing dysplasia, apparently due to the increasing thickness of the upper keratinized layer of the epithelium where the dye was found to localize. Localization in this layer occurred both in the rat palate and in hairless mouse skin. PMID- 11202364 TI - Investigation of cross-resistance to a range of photosensitizers, hyperthermia and UV light in two radiation-induced fibrosarcoma cell strains resistant to photodynamic therapy in vitro. AB - Two distinct photodynamic therapy-resistant variants of the murine radiation induced fibrosarcoma (RIF) cell line have been isolated. One strain displayed relative resistance over the parental RIF-1 strain to treatment with the porphyrin-based compound, polyhaematoporphyrin (PHP), whereas the other strain displayed relative resistance over the RIF-1 strain to treatment using the cationic zinc (II) pyridinium-substituted phthalocyanine (PPC). The PHP-resistant strain did not display cross-resistance to PPC-mediated treatment, and vice versa. In both PDT-resistant strains, the increased resistance could not be attributed to altered cellular growth rate, antioxidant capacity or intracellular sensitizer localization. The PHP-resistant strain displayed resistance to treatment with both short (1 h) and extended (16 h) sensitizer incubation periods, which may indicate that in this strain, the resistance has arisen through an alteration in a membrane component. Conversely, the PPC-resistant strain only displayed increased resistance over the parental cells to treatment involving the short drug incubation, which is likely to reflect the existence of a threshold effect caused by the alteration of an individual cellular target. Each resistant strain has been compared to the parental strain in terms of cellular sensitivity to treatment with a range of other photosensitizers, hyperthermia, UV light and the anticancer agent cis-diamminedichloroplatinum. The PHP-resistant strain exhibited crossresistance to photosensitization treatment using exogenously added protoporphyrin IX, and also to treatment with the anionic phthalocyanine sensitizers, zinc (II) tetrasulfonated phthalocyanine and zinc (II) tetraglycine-substituted phthalocyanine. The PPC-resistant strain did not display cross-resistance to any of the treatment strategies employed in this investigation. The results of this investigation indicate that there are at least two distinct mechanisms of PDT resistance in RIF cells, and that the mechanism of PHP resistance may, to some extent depend, upon the physical nature of the sensitizer molecule. PMID- 11202365 TI - Decreased efficiency of trypsinization of cells following photodynamic therapy: evaluation of a role for tissue transglutaminase. AB - Identifying the cellular responses to photodynamic therapy (PDT) is important if the mechanisms of cellular damage are to be fully understood. The relationship between sensitizer, fluence rate and the removal of cells by trypsinization was studied using the RIF-1 cell line. Following treatment of RIF-1 cells with pyridinium zinc (II) phthalocyanine (PPC), or polyhaematoporphyrin at 10 mW cm-2 (3 J cm-2), there was a significant number of cells that were not removed by trypsin incubation compared to controls. Decreasing the fluence rate from 10 to 2.5 mW cm-2 resulted in a two-fold increase in the number of cells attached to the substratum when PPC used as sensitizer; however, with 5,10,15,20 meso tetra(hydroxyphenyl) chlorine (m-THPC) there was no resistance to trypsinization following treatment at either fluence rate. The results indicate that resistance of cells to trypsinization following PDT is likely to be both sensitizer and fluence rate dependent. Increased activity of the enzyme tissue-transglutaminase (tTGase) was observed following PPC-PDT, but not following m-THPC-PDT. Similar results were obtained using HT29 human colonic carcinoma and ECV304 human umbilical vein endothelial cell lines. Hamster fibrosarcoma cell (Met B) clones transfected with human tTGase also exhibited resistance to trypsinization following PPC-mediated photosensitization; however, a similar degree of resistance was observed in PDT-treated control Met B cells suggesting that tTGase activity alone was not involved in this process. PMID- 11202366 TI - Porphyrin bleaching and PDT-induced spectral changes are irradiance dependent in ALA-sensitized normal rat skin in vivo. AB - Photobleaching kinetics of aminolevulinic acid-induced protoporphyrin IX (PpIX) were measured in the normal skin of rats in vivo using a technique in which fluorescence spectra were corrected for the effects of tissue optical properties in the emission spectral window through division by reflectance spectra acquired in the same geometry and wavelength interval and for changes in excitation wavelength optical properties using diffuse reflectance measured at the excitation wavelength. Loss of PpIX fluorescence was monitored during photodynamic therapy (PDT) performed using 514 nm irradiation. Bleaching in response to irradiances of 1, 5 and 100 mW cm-2 was evaluated. The results demonstrate an irradiance dependence to the rate of photobleaching vs irradiation fluence, with the lowest irradiance leading to the most efficient loss of fluorescence. The kinetics for the accumulation of the primary fluorescent photoproduct of PpIX also exhibit an irradiance dependence, with greater peak accumulation at higher irradiance. These findings are consistent with a predominantly oxygen-dependent photobleaching reaction mechanism in vivo, and they provide spectroscopic evidence that PDT delivered at low irradiance deposits greater photodynamic dose for a given irradiation fluence. We also observed an irradiance dependence to the appearance of a fluorescence emission peak near 620 nm, consistent with accumulation of uroporphyrin/coproporphyrin in response to mitochondrial damage. PMID- 11202367 TI - The photochemistry of flutamide and its inclusion complex with beta-cyclodextrin. Dramatic effect of the microenvironment on the nature and on the efficiency of the photodegradation pathways. AB - The photochemistry of the anticancer drug flutamide (FM), 2-methyl-N-[4-nitro-3 (trifluoromethyl)phenyl]propanamide, in homogeneous media and in the beta cyclodextrin (beta-CD) cavity has been investigated. The photoreactivity of the free molecule has been rationalized on the basis of an intramolecular nitro to nitrite rearrangement followed by cleavage of the nitrite intermediate. The twisted geometry of the nitro group with respect to the aromatic plane plays a key role in triggering such a photoprocess. Incorporation of FM in the beta-CD cavity leads to dramatic effects on both the efficiency and the nature of the photochemical deactivation pathways of the guest molecule. A 20-fold increase in the FM photodecomposition quantum yield and the formation of photoproducts originated by both reduction of the nitro group and cleavage of the amide bond were observed in the presence of the macrocycle. Such a behavior cannot be attributed exclusively to the micropolarity of beta-CD and/or to its role as a reactant. The induced circular dichroism spectra and the nature of the photoproducts formed in these experimental conditions provide indications that the photoreactivity in the beta-CD microenvironment could likely be mediated by structural changes of FM upon complexation. PMID- 11202368 TI - Topically applied eicosapentaenoic acid protects against local immunosuppression induced by UVB irradiation, cis-urocanic acid and thymidine dinucleotides. AB - UVB-induced immunosuppression, a promoter of photocarcinogenesis, involves the formation of pyrimidine dimers and cis-urocanic acid (cis-UCA), but reactive oxygen species (ROS) also plays an important role. Eicosapentaenoic acid (EPA) can inhibit photocarcinogenesis, but due to its polyunsaturated nature it is susceptible to oxidative damage by ROS. The antioxidant defense system may therefore be challenged upon ultraviolet-B (UVB) irradiation in the presence of EPA. We investigated whether topically applied EPA in mice could protect against local immunosuppression (contact hypersensitivity response to dinitrofluorobenzene) induced by UVB radiation (1.5 J/cm2), or topically applied cis-UCA (150 nmol/cm2) or thymidine dinucleotides (pTpT) (5 nmol/cm2). The influence of EPA on epidermal lipid peroxidation and antioxidant status was also measured. UVB irradiation, cis-UCA and pTpT all caused 70% immunosuppression. Topical pretreatment of mice with EPA partially protected against immunosuppression; the EPA dose needed to accomplish this was 10 nmol/cm2 for UVB irradiation, 100 nmol/cm2 for cis-UCA and 1000 nmol/cm2 for pTpT. Higher EPA doses caused higher UVB-induced lipid peroxidation and lower vitamin C levels. Glutathione only decreased with the highest EPA dose whereas vitamin E was not decreased after UVB irradiation. In conclusion, topically applied EPA protects against UVB-, cis-UCA- and pTpT-induced immunosuppression and maintenance of an adequate antioxidant defense seems to be an important prerequisite for the protective action by EPA. PMID- 11202369 TI - Studies of all-trans-retinal as a photooxidizing agent. AB - The photophysical properties of all-trans-retinal (RAL) have been extensively studied because of the importance of the retinoids in the visual process. However, little information is available regarding the participation of RAL in photochemical transformations such as photoxidation. RAL is one of several native chromophores that have been suggested to act as photosensitizers of damage in the human retina, and this damage would likely occur through oxidative pathways. Time resolved and steady state techniques have been used to examine the photoreactivity of RAL toward several suitable substrates. The lifetime of the RAL triplet excited state is observed to decrease with increasing concentration of the well-known electron and hydrogen atom donors, 2,3,5,6-tetramethyl-1,4 phenylenediamine (DAD), hydroquinone (HQ), methylhydroquinone (MHQ), 2,3 dimethylhydroquinone (DMHQ) and trimethylhydroquinone (TMHQ), although the bimolecular rate constants for the reaction are much less than that of diffusion controlled (2.9 x 10(7) M-1 s-1, 1.2 x 10(5) M-1 s-1, 1.2 x 10(5) M-1 s-1, 1.5 x 10(5) M-1 s-1 and 1.6 x 10(6) M-1 s-1, for DAD, HQ, MHQ, DMHQ and TMHQ, respectively). In the presence of the donors, new absorptions grow concomitant with the decay of the triplet excited state, and for DAD and TMHQ, the observed spectra are similar to the spectra of p-phenylenediamine and TMHQ radicals. Irradiation of RAL in argon-saturated methanol results in fairly efficient photobleaching of RAL and in the formation of two new compounds having absorption spectra that are shifted below 300 nm. Irradiation of RAL in argon-saturated acetonitrile also results in photobleaching of RAL, but the reaction proceeds at a slower rate. PMID- 11202370 TI - Light-induced starch degradation in non-dormant turions of Spirodela polyrhiza. AB - Continuous red light controls starch degradation in turions of Spirodela polyrhiza [Dolger, K., U. K. Tirlapur and K.-J. Appenroth [1997] Photochem. Photobiol. 66, 126-127 (1997)]. This light could be replaced by repeated red light pulses with the reciprocity law fulfilled over a large range of fluence rates. The effect of red light pulses repeated every 24 or 12 h for 6 days was reversible by subsequent far-red light pulses. In contrast, hourly applied red pulses were irreversible by far-red light. This discrepancy was explained by showing the starch degradation activity of far-red pulses themselves. The investigated process was categorized as a phytochrome low fluence response with an unusual property: requirement of light treatment for several days. A partial fulfillment of this requirement was obtained with a red pulse followed by a dark period and a 24 h continuous irradiation. These results suggest the existence of two separate steps in the process of starch degradation in turions: formation of a sprout (= sink) during the pulse-induced germination, and starch degradation in the storage tissue (= source) induced by the second light treatment. PMID- 11202371 TI - Attenuation of DNA damage in the dermis and epidermis of the albino hairless mouse by chronic exposure to ultraviolet-A and -B radiation. AB - Mammalian skin is vulnerable to the photocarcinogenic and photoaging effects of solar UV radiation and defends itself using a variety of photoprotective responses including epidermal thickening, tanning and the induction of repair and antiradical systems. We treated Skh-1 albino hairless mice for 60 days with ultraviolet-A (UVA) or ultraviolet-B (UVB) radiation and measured the frequency of cyclobutane pyrimidine dimers and pyrimidine(6-4)pyrimidone photoproducts induced by a single acute sunburn dose of UVB at different stages of the chronic treatment. We found that both UVA and UVB exposure produced a photoprotective response in the dermis and epidermis and that the degree of photoproduct attenuation was dependent on dose, wavelength and the type of damage induced. Although epidermal thickening was important, our data suggest that UV protective compounds other than melanin may be involved in mitigating the damaging effects of sunlight in the skin. PMID- 11202372 TI - Equal-quantum action spectra indicate fluence-rate-selective action of multiple photoreceptors for photomovement of the thermophilic cyanobacterium Synechococcus elongatus. AB - Unicellular thermophilic cyanobacterium Synechococcus elongatus displayed phototaxis on agar plate at 55 degrees C. Equal-quantum action spectra for phototactic migration were determined at various fluence rates using the Okazaki Large Spectrograph as the light source. The shapes of the action spectra drastically changed depending on the fluence rate of the unilateral monochromatic irradiation: at a low fluence rate (3 mumol/m2/s), only lights in the red region had significant effect; at a medium fluence rate (10 mumol/m2/s), four major action peaks were observed at 530 nm (green), 570 nm (yellow), 640 nm (red) and 680 nm (red). At high fluence rates (30-90 mumol/m2/s), the former two peaks remained, while red peaks at 640 nm and 680 nm disappeared and, interestingly, an action peak around 700-740 nm (far-red) newly appeared. These results indicate that two or more distinct photoreceptors are involved in the phototaxis and that suitable photoreceptors are selectively active in response to the stimulus of light fluence rates. Far-red or red background lights irradiated vertically from above drastically inhibited phototaxis toward red light or far-red light, respectively. These results indicate involvement of some phytochrome(s). PMID- 11202373 TI - Celiotomy closure via permanent implantation of polyamide in horses. AB - Permanent implantation of nonabsorbable materials is appropriate in many surgical circumstances but is not commonly used to close equine celiotomies. This paper describes a simple method of continuous nonabsorbable implantation of polyamide suture used successfully to close 48 equine celiotomies. Forty-eight clean or clean-contaminated celiotomies were successfully performed over 5 years using this technique. The postsurgical survival observation period ranged from 1-6 years (median 3.5 years). There were 45 long-term survivors (93.75%). Only 2 minor implant complications (4.4%) were observed and successfully corrected. This study demonstrates that appropriately prepared nonabsorbable polyamide suture can be used for safe and cost effective closure of clean and clean-contaminated equine celiotomies. PMID- 11202374 TI - The medical management of eight horses with grade 3 rectal tears. AB - Eight horses with Grade 3b rectal tears of the peritoneal part of the rectum or small colon were treated by a combination of medical therapy and dietary manipulation. All of the horses developed septic peritonitis during the course of treatment. Medical therapy consisted of a combination of penicillin, gentamicin and flunixin meglumine administered parenterally, metronidazole administered orally and liquid paraffin administered by nasogastric tube. Some horses also received fluid and electrolyte therapy i.v., plasma and heparin i.v. All horses were maintained on a laxative diet. Six of the 8 horses recovered. Duration of therapy in the horses that survived was between 2 and 7 weeks. Three of the 6 horses that recovered developed a rectal diverticulum, which did not appear to cause any subsequent medical problems. In the 2 horses that died, the Grade 3 rectal tear progressed to a Grade 4 tear with subsequent faecal contamination of the abdomen. Manual evacuation of the cavity of the rectal tears during treatment and size of the tears were identified as possible causes for the progression of the disease in these 2 horses. PMID- 11202375 TI - Equine lymphocytic-plasmacytic enterocolitis: a retrospective study of 14 cases. AB - Lymphocytic-plasmacytic enteritis (LPE) is a morphological diagnosis given to a type of infiltrative intestinal disease classified within the complex of idiopathic inflammatory bowel disease (IBD). The purpose of this retrospective study was to describe the details of breed, age and sex, clinical and clinicopathological findings and outcome of horses diagnosed with LPE. Data were reported from 14 horses that had a histopathological diagnosis of LPE; the median age was 12 years, and there was no breed or sex predilection. Common clinical signs were weight loss (100%), diarrhoea (50%) and lethargy (50%). Hypoproteinaemia and hypoalbuminaemia were present in 6/13 (46%) and 9/12 (75%) horses, respectively. Results of the oral glucose tolerance tests or D-xylose absorption tests were abnormal in 9/12 (75%) horses and rectal mucosal biopsies were abnormal in 3/7 (43%) horses. Corticosteroid treatment was used unsuccessfully in 4 horses. All horses were subjected to euthanasia and LPE was diagnosed at necropsy. Diffuse thickening of the small intestine was apparent grossly in 10/13 (77%) horses examined. LPE is an uncommon equine intestinal disease that is difficult to diagnose antemortem and has a poor prognosis. PMID- 11202376 TI - Prognostic indicators in a Danish hospital-based population of colic horses. AB - A prospective survey of 528 colic horses, referred to the Large Animal Hospital at the Royal Veterinary and Agricultural University of Copenhagen, Denmark, during the period August 1994 to December 1998, was undertaken to develop a predictive model for application in the clinical assessment of prognosis. In the multivariate logistic regression analysis, 357 colic cases were used in the elaboration of a simple clinical-practical model consisting of degree of pain, packed cell volume, capillary refill time and rectal temperature. The relationship between rectal temperature and outcome (survival/death) has been regarded as linear. It has also been reported to be nonsignificant. The present study suggests a strong U-shaped relation, which is easily transformed into a linear association and readily interpretable in the clinical situation if treated as a deviation from 38 degrees C. Several other clinical and laboratory variables were strongly related to outcome in the bivariate analysis. The changes in sensitivity and specificity of the multivariate model, when applied as a prognostic test, were presented with changing cut-off values. The cut-off value is the level, of predicted probability of death, at which the clinical decision to treat or subject to euthanasia is taken. The predictive performance of the model was further illustrated using a mortality of 19%. The optimal accurate classification for both survival and death was 87%, which was attained when a cut off value of 86% was selected. To minimise the number of horses unnecessarily subjected to euthanasia, the cut-off value was increased. However, this simultaneously increased the number of misclassified survivors, i.e. the number of horses that would die despite treatment. Outcome was especially poorly predicted in 4 horses, as was indicated by extreme deviance residuals. In 2 of these horses the large residuals were attributable to sudden and severe changes in the course of disease. All 4 horses had changes in variable values towards abnormality prior to death. Repeated measurements are therefore suggested in order to increase the test performance in general. The prerequisites of clinical application of prognostic models are critically discussed. The main findings of the present study indicate that degree of pain, packed cell volume, capillary refill time and temperature deviation from 38 degrees C, used in a logistic regression model, offer a strong model for clinical assessment of prognosis. PMID- 11202377 TI - Hypercoagulation and hypofibrinolysis in horses with colic and DIC. AB - Changes in haemostasis in horses with colic were assessed by using specific and sensitive markers of coagulation and fibrinolysis activity. Blood samples from 41 horses with severe colic and from 30 healthy control horses were tested. Diagnosis of DIC was based on the findings of at least 3 of 6 abnormalities: thrombocytopenia, prolonged clotting times (PT and APTT), increased polyclonal FDPs, decreased fibrinogen and decreased AT-III activity. Plasma thrombin antithrombin III complexes (TAT), monoclonal fibrin degradation products fragment D (D-dimer) and monoclonal fibrinogen degradation products (FgDP) were also tested by using ELISA kits. DIC was diagnosed in 16 of 41 horses with colic. Compared to control and non-DIC colic values, TAT was significantly (P < 0.000) greater in horses with colic and DIC (Control group, mean +/- s.d. 2.6 +/- 2; non DIC colic group, 7.5 +/- 9, and DIC colic group, 30.9 +/- 36 ng/ml). Also, D dimer was significantly (P < 0.000) less in the DIC group when compared to control and non-DIC colic values (mean +/- s.d. 677 +/- 119, 682 +/- 220 and 399 +/- 234 ng/ml, respectively). Compared to non-DIC colic values, FgDP was significantly (P < 0.05) lower in the DIC group (363 +/- 111, 437 +/- 230 and 293 +/- 187 ng/ml respectively). Both PT and APTT showed a significant positive correlation with TAT. DIC was more common among nonsurvivors and horses with ischaemic bowel. We conclude that a hypercoagulative state was detected in horses with colic, which was stronger in horses with colic and DIC. Hypofibrinolysis was present only in horses with DIC. Therefore, marked hypercoagulation together with hypofibrinolysis are associated with DIC in horses. PMID- 11202378 TI - Effect of eltenac in horses with induced endotoxaemia. AB - Ten horses were used in a crossover study to evaluate the effectiveness of eltenac against endotoxaemia. Eltenac (0.5 mg/kg bwt) or saline control was given i.v. then 15 min later, intravenous infusion of endotoxin was begun and continued for 120 min (total dose 100 ng/kg bwt). Horses were monitored for heart and respiratory rates, pulmonary and carotid arterial pressure and core body temperature. Blood was sampled at intervals for measurement of haematological variables and plasma concentrations of lactate, prostanoid metabolites, tumour necrosis factor (TNF) and stress hormones. In comparison with saline-treatment, use of eltenac significantly protected against endotoxin-induced changes in respiratory rate, core temperature, systemic arterial blood pressure (SAP), pulmonary arterial pressure, PCV, and plasma protein, 6-keto prostaglandin F1 alpha, thromboxane B2, epinephrine, and cortisol concentrations. Despite statistical effect of eltenac on SAP, values in both treatment groups remained well above baseline throughout the evaluation period. Significant protective effect of eltenac was not found for heart rate, white blood cell count, plasma lactate concentration or TNF activity. On the basis of these results, it is expected that use of eltenac will provide clinical benefit in horses with naturally occurring endotoxaemia. PMID- 11202379 TI - Colic surgery in 206 juvenile thoroughbreds: survival and racing results. AB - The purpose of our study was to determine the types of lesions that cause colic in juvenile Thoroughbreds, factors associated with these lesions and the subsequent survival and athletic performance of the juveniles. The age of juvenile Thoroughbreds requiring surgical exploration for abdominal pain has an influence on the type of lesion causing colic. The short-term survival rate (discharge from the hospital) after colic surgery for foals was 85% and was strongly influenced by the lesion causing colic. Thirteen percent of juveniles recovered from the first surgery experienced another severe colic episode requiring additional surgery or euthanasia. Eight percent of foals recovered from the first celiotomy developed adhesions. Adhesion formation was related to the initial lesion causing colic and the foals' age at the first surgery. Foals being suckled (15 days to 6 months) were at greatest risk for adhesions and more frequently required multiple surgeries. Juvenile Thoroughbreds that had a celiotomy were significantly less able to race (63%) than their unaffected siblings (82%), and age at the initial surgery was associated with the percentage of horses that raced. However, affected foals able to race won as much money, raced as often, and made as many starts as their siblings. Colic and surgical treatment have a negative impact on athletic performance, but the majority of foals discharged from the hospital after colic surgery will perform athletically as adults. PMID- 11202380 TI - Investigation of an outbreak of tapeworm-associated colic in a training yard. AB - A novel serological assay which measures IgG(T) specific for a 12/13 kDa protein of the equine tapeworm Anoplocephala perfoliata was used as part of a colic outbreak investigation. A training/rehabilitation yard for Thoroughbreds and Arabs was found to have an increasing incidence of colic over a 5 year period, culminating in a peak incidence of 1.15 episodes/horse year at risk. Four animals suffered from ileal impaction colic which necessitated surgical management. A case-control study design suggested a strong association between tapeworm infection and colic, with evidence of a dose-response relationship. Intervention, in the form of anticestode anthelminthics, coincided with a decrease in the incidence of colic and a fall in anti-12/13 kDa IgG(T) antibody levels of 8 horses monitored post-treatment. This study demonstrates that anthelminthic regimens, using exclusively ivermectin, may lead to an increase in tapeworm infection intensity which may in turn lead to an increased incidence of colic. Furthermore, it provides support to the hypothesis that the risk of ileal impaction colic and spasmodic colic increases with tapeworm infection intensity. The practical application of the anti-12/13 kDa IgG(T) ELISA is demonstrated by this study. PMID- 11202381 TI - The pursuit of knowledge and where it leads us. PMID- 11202382 TI - Short- and long-term survival and prevalence of postoperative ileus after small intestinal surgery in the horse. AB - The records of 74 horses that recovered from anaesthesia after surgery for a small intestinal lesion from 1994 to 1999 were reviewed. Sixty-three horses (85%) had a strangulating lesion and 43 of these (68%) had a resection and anastomosis. Four of 11 horses (36%) without a strangulating lesion had a resection and anastomosis. Sixty-three horses (85%) survived to discharge, with a survival rate of 53/63 in horses with a strangulating lesion (84%) and 10/11 (91%) in others. For all lesions, short-term survival for all end-to-end anastomoses (91%; 21/23) and for no resection (92%; 23/25) were superior (P < 0.05) to survival for jejunocaecal anastomosis (76%; 19/25). Fourteen horses (19%) had a repeat abdominal surgery during hospitalisation; 9 of these (64%) survived short-term. Postoperative ileus developed in 7/70 horses (10%) after surgery for a problem other than proximal enteritis, and all had a strangulating lesion. Postoperative ileus (POI) was more likely after a jejunocaecostomy than after other procedures, and did not develop after a jejunojejunostomy. Survival > 7 months was 52/69 (75%) and for > 12 months was 39/57 (68%). The estimated prevalence of adhesions was 13%. Short-term survival was poorest in horses that had a jejunocaecostomy, but long-term survival was less affected by the anastomosis used. The sharpest decline in survival was during the first postoperative week and postoperative mortality then declined over time after surgery. A postoperative protocol that allowed early postoperative feeding was well tolerated. The results confirm that the overall prognosis after small intestinal surgery in horses is improved over earlier findings. PMID- 11202383 TI - Effect of extensive ileal resection with a large resulting mesenteric defect and stapled ileal stump in horses with a jejunocaecostomy: a comparison with other anastomotic techniques. AB - Extensive resection of the ileum of the horse, using automated stapling equipment followed by a stapled jejunocaecostomy, without closure of the mesenteric defect, was evaluated prospectively as a surgical treatment for lesions involving the distal small intestine. Of 153 horses treated surgically for colic, 10 horses with strangulating lesions involving the distal ileum were treated by extensive resection and jejunocaecal anastomosis leaving a residual mesenteric defect. These were compared with 12 horses with jejunoileal lesions treated by jejunocaecal anastomosis with closure of the mesentery, and 19 horses with distal jejunal lesions treated with an end-to-end jejunojejunal anastomosis and mesenteric closure. Long-term (> 7 months) and short-term survival, duration of surgery, length of intestine resected, time from completion of surgery until the horse first defaecated and the highest recorded postoperative plasma fibrinogen level were assessed. There were no significant differences between the surgical techniques for any of the assessed parameters, but there was a trend to significance with a higher death rate following discharge from the hospital when cases of jejunocaecal anastomosis with a residual mesenteric defect were compared to cases of end-to-end jejunojejunal anastomosis with closure of the mesentery (P = 0.06). This study suggests that a stapled distal ileal resection and jejunocaecal anastomosis leaving a residual mesenteric defect is a satisfactory technique when pathological changes necessitate resection of the distal ileum. However, in this study, jejunocaecal anastomosis with or without mesenteric closure produced inferior results compared to jejunojejunal anastomosis. PMID- 11202384 TI - The role of cyclooxygenase inhibitors in repair of ischaemic-injured jejunal mucosa in the horse. AB - Cyclooxygenase inhibitors are administered to horses to prevent endotoxin-induced elaboration of prostaglandins. However, PGE2 and PGI2 stimulate repair of injured intestine. There are 2 isoforms of cyclooxygenase: COX-1, which constitutively produces prostaglandins and COX-2, which is induced by inflammation. We hypothesised that the nonspecific cyclooxygenase inhibitor flunixin meglumine would retard repair of ischaemic intestinal injury by preventing production of reparative prostaglandins, whereas the selective COX-2 inhibitor, etodolac, would permit repair as a result of continued COX-1 prostaglandin production. Segments of equine jejunum were subjected to ischaemia for 1 h, and recovered for 4 h in Ussing chambers. In ischaemic tissue, treated with the nonspecific cyclooxygenase inhibitor, flunixin meglumine (2.7 x 10(-5) mol/l), production of PGE2 and PGI2 was inhibited, and there was no evidence of recovery based on measurements of transepithelial resistance. Conversely, untreated ischaemic tissues or tissues treated with the specific COX-2 inhibitor etodolac (2.7 x 10(-5) mol/l) had significant elevations in PGE2 and PGI2, and significant recovery of transepithelial resistance. These studies suggest that specific COX-2 inhibitors may provide an advantageous alternative to nonspecific cyclooxygenase inhibitors in horses with colic. PMID- 11202385 TI - Putting theory into practice. PMID- 11202386 TI - Diagnosis and treatment of chronic recurrent caecal impaction. AB - Ninety-six horses with chronic recurrent caecal impaction associated with hypertrophy of muscle layers in the caecal base or in the whole caecum were examined from 1990 to 1996. Enlargement of the caecocolic orifice was completed surgically in 58 horses. Of those horses having surgery, 50 were discharged from the hospital while 8 were subjected to euthanasia at the hospital due to complications. Twenty-seven of the 50 horses discharged were normal at follow-up while 23 died or were subjected to euthanasia due to acute or recurrent colic, recurrent impaction in the ascending or descending colon, complete caecal muscle layer hypertrophy, stomach rupture or lymphosarcoma. Approximately 50% of the cases were successfully treated by surgical enlargement of the caecocolic orifice. The results suggest, on the other hand, that enlargement of the caecocolic orifice was not successful in treating horses with hypertrophy of the caecal muscle layer in the whole caecum. PMID- 11202387 TI - Muscle thickness and neuron density in the caecum of horses with chronic recurrent caecal impaction. AB - In this study, the hypothesis that caecal smooth muscle layers would be thinner and the linear neuron density of myenteric plexus greater was tested in normal horses compared to those with chronic recurrent caecal impaction. Four normal horses and 18 horses with chronic recurrent caecal impaction were subjected to euthanasia and 7 tissue samples were collected from each horse at different regions of the caecum (apex, dorsal body, cranial base, dorsal base, caudal base, caudal body, ventral body). Twelve horses with chronic recurrent caecal impaction were treated surgically. Only one tissue sample of the cranial part of the caecal base close to the caecocolic orifice was taken during surgery. The thickness of the circular muscle layer of all caecal regions measured in killed horses with chronic recurrent caecal impaction was significantly increased compared to the equivalent caecal region of normal horses. On the other hand, the longitudinal muscle layer was significantly thicker only in the cranial and caudal caecal base and in the dorsal region of the caecal body. The linear neuron densities of all caecal base areas and 2 caecal body regions, the caudal body region and of the apex, of killed horses with chronic recurrent caecal impaction were significantly lower compared with those in clinically normal horses. The circular muscle layer of all caecal regions was thickened (hypertrophied) probably as a consequence of chronic uncoordinated hypercontractility due to neuron deficit in the myenteric plexus of the caecal base. PMID- 11202389 TI - Caecocaecal and caecocolic intussusceptions associated with larval cyathostomosis in four young horses. AB - This report describes the clinical and pathological features of 4 horses affected by caecocaecal or caecocolic intussusceptions associated with larval cyathostomiasis. In each case, there was clinical and/or pathological evidence of concurrent larval cyathostomosis. They all demonstrated variable signs including diarrhoea, pyrexia, weight loss and subcutaneous oedema and cyathostome larvae were identified in the faeces of 3 of the horses. These cases highlight the need to consider caecal intussusceptions as a possible complication in horses affected by larval cyathostomosis, especially where signs of abdominal pain are severe or persistent. PMID- 11202388 TI - Caecal impactions managed surgically by typhlotomy in 10 cases (1988-1998). AB - Surgical management of caecal impactions has included several different procedures suggested over the years. Complete bypass of the caecum through an ileocolic or jejunocolic anastomosis has become common practice for first time caecal impaction management, especially when dysfunction is suspected. In our practice, however, caecal impactions have been managed surgically by typhlotomy alone and of the 10 cases (July 1988-June 1998), 9 underwent surgery for first time caecal impactions, received a typhlotomy, and had survived an average of 43 months at time of case review. At the time of surgery, all were considered to have a dysfunctional caecum. All horses received routine postoperative care with the addition of anthelmintics as recovery of Anoplocephala perfoliata occurred in several cases. Typhlotomy should be considered an acceptable technique for surgical management of first time caecal impactions. Postoperative pyrantel pamoate and larvicidal anthelmintics should also be considered. PMID- 11202390 TI - Intestinal motility and impactions. PMID- 11202391 TI - Design and clinical use of a modified colon tray for large colon evacuation in the horse. AB - A modified colon tray to perform large colon evacuations in horses was designed. A funnel-shaped accessory was constructed to create a mechanical separation between the sterile and nonsterile part of the tray. Sterile hooks were used to make a temporary and stabile colostomy. Thirty horses with surgical correction of nonstrangulating large colon obstruction underwent a large colon evacuation with this modified tray. The surgical procedure was uncomplicated and resulted in a positive outcome in 29 horses. This less labour-intensive way to evacuate the large colon results in minor contamination and makes extraluminal lavage becomes superfluous. This modified tray is a very efficacious and practical instrument for emptying the large colon in horses. PMID- 11202392 TI - Segmental eosinophilic colitis: a review of 22 cases. AB - Twenty-two horses with colic, referred to the University of Liverpool Equine Hospital (1992-1998), were found at laparotomy to have a partial obstruction of the large colon caused by a segmental mural lesion located in the left dorsal colon. The decision to take the horses to surgery was based on rectal examination findings of secondary impaction and mural oedema of the large colon and turbid peritoneal fluid containing large numbers of neutrophils obtained by paracentesis. The affected segment of colon showed oedema and serosal changes varying from erythema to well-defined necrosis. These pathological changes were considered to be sufficiently severe in 16 horses to merit partial resection of the left colon. Histology revealed varying degrees of mucosal necrosis, marked submucosal oedema and infiltration with large numbers of eosinophilic leucocytes. No cause was identified for the lesions. Sixteen of the 18 horses discharged from the hospital were alive 3 months to 7 years after surgery and have returned to their previous type of work and level of performance. The remaining 2 horses were subjected to euthanasia because of a recurrence of colic but no autopsy was performed. PMID- 11202393 TI - Nephrosplenic entrapment in the horse: a retrospective study of 174 cases. AB - The clinical findings and outcome of 161 horses diagnosed with 174 episodes of nephrosplenic entrapment (NSE) were reviewed retrospectively. The median age at presentation was 5 years (9 months to 24 years), and duration of colic was 2-92 h. Nasogastric reflux was present in 49 of 113 horses (43.4%) and was significant (> or = 21) in 32 (28.3%) horses. The recurrence rate was 13/161 (8.1%). Thirteen horses (13/174, 7.5%) had other lesions including small intestinal obstruction (4), 360 degrees large colon torsion (5), gastric rupture (2), thromboembolic colic (1) and small colon infarction (1). Of 115 cases, in 107 horses treated by surgery alone, 2 horses required a large colon resection, and 8 (8/107, 7.5%) horses died or were subjected to euthanasia. Twenty-six of 35 horses (74%) were successfully corrected by rolling under general anesthesia and, of the 9 horses taken to surgery after rolling, 4 had other lesions and 2 were corrected at surgery. Phenylephrine was used in 20 of 35 horses that were rolled and 2 horses required surgery after rolling with phenylephrine. Five horses were jogged after phenylephrine administration and all were successfully corrected. Eleven horses presented with the left colon located between the spleen and the body wall were treated successfully by fasting and/or i.v. fluids. One horse had a gastric rupture after rolling. The overall success rate was 92.5%. In conclusion, NSE is a condition associated with a good prognosis for medical or surgical correction. A small number of horses may have additional gastrointestinal lesions, which may affect outcome. PMID- 11202394 TI - Evaluation of uniformity of morphological injury of the large colon following severe colonic torsion. AB - This report describes the evaluation of uniformity of morphological injury of the large colon following severe colonic torsion in 17 horses presented to the Veterinary Medical Teaching Hospital. In 16 horses, twist occurred at the colonic base and in 1 at the sternal and diaphragmatic flexure. Eleven of the 17 horses were subjected to euthanasia at surgery and 6 of 17 following surgical correction within 4 days postoperatively. The objective of this study was to determine if the degree of histological changes present at the pelvic flexure were uniformly distributed throughout the regions of the colon involved in cases of severe colonic torsion. PMID- 11202395 TI - [Specifics of realization of general bioethical principles in military medicine]. PMID- 11202396 TI - [Actual problems of technical and metrological support of the extreme medicine service in Russia]. PMID- 11202397 TI - [Principles of diagnosis formulation based on requirements of the International statistical classification of diseases and health-related problems]. PMID- 11202398 TI - [Pharmacoeconomic aspects of therapy of pneumonia in a hospital]. AB - In the article the assessment of hospital treatment cost of patients with pneumonia under conditions of district military clinical hospital is given. The analysis of cost of complete treatment course has shown that the most expensive is therapy of patients with severe and moderately severe pneumonia (6083 and 4608 rubles). Depending on pneumonia severity the treatment expenses increases on the average by 49%. The main treatment expenses in pneumonia under hospital conditions are medical-and-diagnostic, which determine the other items of expenditure. PMID- 11202399 TI - [Rotational digital subtraction angiography for selective investigation of autovenous aortocoronary shunts in patients with coronary heart disease]. PMID- 11202400 TI - [The role of blood alcohol dehydrogenase in pathological alcohol involvement]. AB - The authors have revealed the distinct parallelism between clinical state of patients with alcoholism, activity of alcohol dehydrogenase (ADG) in their blood plasma and presence of signs of pathologic inclination for alcohol (PIA). The marked PIA signs were accompanied by high ADG activity in blood. It permits to combine the presence of PIA and enzyme high activity into single pathogenetic mechanism and suggest that together with metabolic function ADG performs the receptor one. Also it is possible to assume that use of drugs decreasing ADG activity and restoring ethanol content in organism of patients with alcoholism will contribute to PIA release. Use of such drugs can become one of the safe methods in alcoholism therapy. PMID- 11202401 TI - [Therapeutic efficacy of Ruzam+ cream]. PMID- 11202402 TI - [Infectious dermal lesions in malignant lymphomas]. PMID- 11202403 TI - [A novel method of cystoplasty after cystectomy in cancer]. AB - A new method of cystoplasty with free musculocutaneous graft on vascular crus was developed and introduced into clinical practice. This method satisfies the requirements necessary for artificial urinary bladder that are created from the segment of small intestine and considered as a "gold standard" in the treatment of such pathology. Good anatomic-and-functional results (urination way usual for the patient is remained, the volume of reservoir being created is sufficient, low urine pressure, anti-reflux mechanism and preservation of upper urinary tracts) permit to recommend the method for clinical study and use. PMID- 11202404 TI - [New approaches to organization and medical examination of servicemen (Experience of the 52d Consultative and Diagnostic Center of Department of Defence of the Russian Federation]. AB - New approaches to organization and conduction of prophylactic medical examination of servicemen were developed, scientifically grounded and introduced into the practice in Consulting-and-diagnostic Center N 52 of RF MD. Owing to it the quality and effectiveness of prophylactic examination have increased, the real picture concerning the health of contingents being served (passport of health) was obtained, the duration of profound medical examination, financial expenses and trained resources for conduction of profound medical examination and regular medical check-up with significant improvement of their quality have minimized. PMID- 11202405 TI - [Mobile medical units for rendering first medical aid]. PMID- 11202406 TI - [Modern preparations for medical prophylaxis]. PMID- 11202407 TI - [Rights and privileges of blood donors]. PMID- 11202408 TI - [Organization of the surgical care of the wounded during the beginning of the World War II]. PMID- 11202409 TI - [N. I. Pirogov's relics in the Museum of Military Medicine (on the 190th birthday of N. I. Pirogov)]. PMID- 11202411 TI - Polymorphism of gonadotropin action: clinical implications. AB - It has recently became apparent that the structural heterogeneity of gonadotropin molecules can contribute to variations of their action in different physiological and pathophysiological conditions. One reason for the structural variations of circulating gonadotropin molecules is the microheterogeneity caused by the variability of glycosylation of individual gonadotropin molecules. The carbohydrate moieties of gonadotropins are important for their intrinsic bioactivity, as reflected by measurement of their bioactivity to immunoreactivity (B/I) ratios. We have reassessed this phenomenon by improved in vitro bioassay and immunoassay methods, and it appears that the intrinsic bioactivity of gonadotropins, in particular of LH, is more constant than previously assumed. Many of the previously documented differences, some even considered diagnostic for certain clinical conditions, have turned out to be methodological artifacts. The first part of this review summarizes our recent findings on the B/I ratios of LH, with special reference to the male. The second part of this review describes a common polymorphism that was recently discovered in the gene of the LH beta subunit. The variant LH beta allele contains two point mutations, which introduce to LH two amino acid changes and an extra glycosylation site. The LH variant is common world-wide, with carrier frequency varying from 0 to 52% in various ethnic groups. The LH variant differs functionally from wild-type LH, and it seems to predispose its carriers, both men and women, to mild aberrations of reproductive function. It is important for the clinician to be aware of this variant LH form, not detected by all immunoassays, because it may explain some aberrant results of LH measurements in patient samples. PMID- 11202412 TI - Long-term administration of large doses of paracetamol impairs the reproductive competence of male rats. AB - AIM: To evaluate the antireproductive effect of paracetamol in male rats. METHODS: Male rats were orally administered daily with 500 mg/kg or 1000 mg/kg of paracetamol for 30 consecutive days. Their sexual behaviour and fertility were evaluated using receptive females. RESULTS: At 2 h after treatment, sexual behaviour was not inhibited but on day 30 both doses of paracetamol caused marked impairment of libido (assessed by % mounting, % intromission and % ejaculation), sexual vigour (number of mounts and intromissions and copulatory efficiency) or sexual performance (intercopulatory interval). In mating experiments, the fertility (in terms of quantal pregnancy, fertility index, implantation index and number of implants) was significantly reduced. All these effects were reversible. The antireproductive effect was not due to a general toxicity but due to an increase in pre-implantation losses resulting from oligozoospermia, impairments of normal and hyper-activated sperm motility, and reduction in the fertilizing potential of spermatozoa. CONCLUSION: Long-term use of high doses of paracetamol may be detrimental to male reproductive competence. PMID- 11202414 TI - Xenoesterogens and male infertility: myth or reality? AB - AIM: To evaluate the role of polychlorinated biphenyls (PCBs) as a potential environmental hazard in the deterioration of male fertility. METHODS: Fifty-three males were studied. After a thorough case history evaluation and relevant clinical and laboratory investigations, PCBs were estimated in the seminal plasma of 21 infertile men with "Unexplained Male Factor" and 32 fertile controls. Peak retention times of the eluants were compared with those of the commercially available standard PCB Mix, and the results confirmed spectrophotometrically. Seminal PCB concentrations were compared between i) fertile and infertile men and ii) men from different areas and diets. The relationship between PCB concentrations and measures of sperm quality such as the total motile sperm count, was assessed. RESULTS: PCBs were detected in seminal plasma of infertile men but absent from controls. Sperm quantity and quality were significantly lower in infertile men compared to controls. The highest average PCB concentrations were found in fish-eating urban dwellers, and followed in succession by fish eating rural dwellers, non fish-eating urban dwellers and non fish-eating rural dwellers. The total motile sperm counts were inversely proportional to the PCB concentrations and were significantly lower than those of the respective controls. CONCLUSION: PCBs may be instrumental in the deterioration of sperm quantity and quality, a contaminated fish diet being the main source of exposure. PMID- 11202413 TI - Effect of testicular capsulotomy on secretion of testosterone and gonadotrophins in rats. AB - AIM: In order to clarify further the mechanisms underlying the effect of capsulotomy on testicular function, the levels of testosterone, LH and FSH were observed. METHODS: Intratesticular testosterone levels and LH, FSH levels in the peripheral blood of normal, sham-operated and capsulotomized rats were detected by RIA. RESULTS: After testicular capsulotomy, there was a progressive reduction in the testosterone level in the testicular venous blood together with a progressive increase in the LH and FSH levels in the peripheral blood from approximately 30 days post-capsulotomy. Morphological changes were observed at 5 10 days after capsulotomy, i.e., far ahead of the hormonal changes. CONCLUSION: The seminiferous tubular damage after testicular capsulotomy was not caused by the reduction in testosterone, and on the contrary, the hormonal change might be secondary to the morphological alterations. The increase in LH level most likely resulted from a negative feedback influence from the lowered testosterone level, while the increase in FSH secretion may be a feedback signal of the damaged seminiferous tubules. PMID- 11202415 TI - Production of chicken chimeras by fusing blastodermal cells with electroporation. AB - AIM: To establish techniques for producing somatic and germline chimeric chicken by transferring blastodermal cells fused with electroporation. METHODS: Stage-X blastodermal cells isolated from freshly laid fertile unincubated white Leghorn and Rhode Island red chicken eggs were fused with electroporation. The treated cell suspension was transferred to the recovery medium (DMEM containing 10% FBS) and was injected into the subgerminal cavity of recipient unincubated embryos (stage X). RESULTS: Of 177 recipient embryos injected with the fusing blastodermal cells, 6 (3.4%) survived to hatching. Somatic chimerism was examined in the melanocyte of the feather. The presence of feathers originating from the donor cell was observed in 1 bird (16.7%) out of the 6 hatched birds. After 21 days of incubation two birds out of five embryos were subjected to polymerase chain reaction (PCR) analysis for W-chromosome-specific DNA for each tissue. One bird possessed W-chromosome-specific DNA in the stomach, and the other exhibited the same DNA in the left and right gonads and other tissues, but not the stomach. CONCLUSION: Recipient embryo having electrofused blastodermal cells yields somatic and germline chimeric chickens more successfully. PMID- 11202416 TI - Purification and characterization of rat testicular glutathione S-transferases: role in the synthesis of eicosanoids. AB - AIM: Purification of glutathione S-transferases (GSTs) from rat testis; separation and identification of various subunits and their role in eicosanoid biosynthesis. METHODS: Purification of rat testicular GSTs by affinity chromatography, employing S-hexylglutathione-linked epoxy-activated Sepharose 6B column and separation of individual subunits by reverse phase-high pressure liquid chromatography (RP-HPLC). Characterization of affinity purified GSTs by Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis. The role of testicular GSTs in eicosanoid biosynthesis was determine by incubating GSTs with 5, 6-Leukotriene A4Me (LTA4Me) and prostaglandin H2(PGH2) and analyzing the products formed on HPLC/TLC. RESULTS: The present study reveals that majority of rat testicular GSTs are of Yb size (60%) with molecular weight of 27 kDa. The most predominant subunits, however, are GST Yn2(27%), followed by GST Yc(24%) and GST Yn1(20%). These testicular GSTs showed very high Leukotriene C4 (LTC4) synthase activity with 5, 6-Leukotriene A4Me (LTA4Me) as the substrate and prostaglandin D (PGD) synthase activity with prostaglandin H2(PGH2) as the substrate. CONCLUSION: Majority of rat testicular GSTs are Yb sized and are involved in the synthesis of eicosanoids like LTC4 and PGD2. PMID- 11202417 TI - Low dose gossypol for male contraception. AB - AIM: To ascertain whether the side effects of gossypol, hypokalemia and irreversibility, could be avoided on dose reduction. METHODS: Seventy-seven male volunteers were divided into 3 groups: control (22 cases), 10 mg gossypol (29 cases) and 12.5 mg (26 cases). Serum levels of testosterone, FSH and LH were measured by RIA and potassium by flame photometry. Sperm counts and motility were examined before and regularly after treatment for the evaluation of contraceptive efficacy. RESULTS: The average sperm density and motility started to decrease significantly by the end of month 2 of medication and gradually reached the infertility levels (< 4 million/mL) in both treated groups. After that the 10 mg group was asked to take the same dose every other day for up to a total observation period of 16-18 months for the maintenance of infertility. Subjects in the 12.5 mg group did not take gossypol any more so as to observe the length of the loading dose required, but in a few, a maintenance dose of 12.5 mg every other day was instituted for a few more months. In both treated groups, none of the spouses was pregnant during the maintenance dose period. Serum levels of potassium, FSH, LH and testosterone were not significantly changed and not a single volunteer complained of myoasthenia. After cessation of drug administration, the semen data returned to pretreatment levels. CONCLUSION: A regimen with 10 or 12.5 mg of gossypol as the daily loading dose and 35 or 43.75 mg as the weekly maintenance dose could induce infertility in male volunteers without developing hypokalemia or irreversibility. PMID- 11202418 TI - Inductively coupled plasma emission spectroscopic and flame photometric analysis of goat epididymal fluid. AB - AIM: The elemental composition of the epididymal luminal fluid (ELF) in adult goat (Capra indica) was investigated. METHODS: ELF was collected by micropuncture from twelve sites along the epididymal duct. The elemental contents was analyzed with inductively coupled plasma (ICP) emission spectroscopy, a microanalytical technique that can simultaneously measure many elements in minute volumes of sample. The Na and K concentrations were determined by flame photometry. RESULTS: ICP spectroscopy showed the presence of copper, calcium, nickel, iron, magnesium, chromium, titanium and zinc in ELF, with fluctuating levels at different sites along the length of the epididymis. Cadmium, cobalt, lead and manganese were not found. The Na+/K+ ratio was seen to be higher at the initial segments of the epididymis and lower at the distal. CONCLUSION: It is proposed that the observed characteristic distribution of elements in ELF may have far reaching implications in sperm maturation and storage known to occur in the epididymis. PMID- 11202419 TI - Cytogenetic and andrological status and ICSI-results in couples with severe male factor infertility. AB - AIM: To pursue whether cytogenetic aberrations correlate with specific spermatological or hormonal abnormalities. METHODS: 305 infertile couples were investigated. All male partners were referred to a complete andrological work-up with physical examination, determination of hormones, HIV testing and semen analysis. Cytogenetic analysis was carried out in both partners by means of standard techniques using cultured lymphocytes from peripheral blood. RESULTS: Among the 305 couples, 10 men (3.2%) and 10 women (3.2%) showed constitutional chromosomal aberrations, including reciprocal translocations (n = 7), Robertsonian translocations (n = 3), inversions (n = 3), other structural aberrations (n = 4) and sex chromosome aberration (n = 3). In addition to the impaired sperm count in most of the patients, a tendency to an increased proportion of spermatozoa with acrosome defect was observed. CONCLUSION: Chromosomal aberrations may contribute to the low fertilization and pregnancy rates in the infertile couples. PMID- 11202420 TI - Testicular vasomotion in different mammals. AB - Vasomotion is a rhythmical variation in arterial blood flow present in many different organs among them the rat testis. Vasomotion is suggested to play an important role for the transvascular fluid exchange and the exchange of nutrients over the capillary wall as well as the formation of interstitial fluid. The present study was undertaken to elucidate whether vasomotion is present in the testes of different species independent of their anatomical vascular topography. Blood flow in the testes of mouse, brush-tailed possum, tammar wallaby, ram and human was investigated by using a laser Doppler flowmeter. Vasomotion was found in all the species investigated. PMID- 11202421 TI - A clinical comparative study on effects of intracavernous injection of sodium nitroprusside and papaverine/phentolamine in erectile dysfunction patients. AB - AIM: To study the effect of intracavernous sodium nitroprusside (SNP), a nitric oxide (NO) donor, on penile erection. METHODS: Forty-two patients with erectile dysfunction (ED) were randomly assigned to receive SNP 300 micrograms or the control drugs (papaverine 30 mg + phentolamine 1 mg) intracavernously crosswise one week apart. The penile length, circumference and hardness after the administration of the experimental and control drugs were assessed and compared statistically. RESULTS: (1) There was no significant difference between the changes in penile length and circumference in the two occasions; (2) In 25 SNP and 28 control cases, the hardness of the penis was scored above 100 as evaluated by the Virag method (P > 0.05); (3) The duration of erection in the controls was longer than that in the SNP, but there were three priapism in the controls and not a single one in the SNP; (4) there was no apparent change in the heart rate and blood pressure in both occasions; other side effects were minimal except slight local pain in a few controls. CONCLUSION: SNP facilitates relaxation of the penile smooth muscle and penile erection without significant side effects. SNP may be used in ED patients that experience pain and priapism with papaverine/phentolamine. PMID- 11202422 TI - Penile prosthesis implantation in a transsexual neophallus. AB - Reconstruction surgery for a female to male transsexual usually involves mastectomy, hysterectomy and creating an aesthetically appealing neophallus. We have successfully inserted an inflatable prosthesis using the AMS CX prosthesis in a 45 year old transsexual, who had a large bulky neophallus constructed from the anterior abdominal subcutaneous fat, about 9 years ago. The single cylinder CX prosthesis was well anchored to the symphysis pubis using a dacron windsock tubing, the activation pump was placed in the dependent pouch of the right labium and the reservior in the usual perivesical space. The patient subsequently had debulking procedure using liposuction to create a more aesthetic and functional phallus. To date, the inflatable neophallus prosthesis is functioning well. PMID- 11202423 TI - Androgen receptor isoforms in human and rat prostate. AB - AIM: To investigate the androgen receptor (AR) isoforms and its variability of expression in human and rat prostatic tissues. METHODS: Human benign prostatic hyperplasia (BPH) and prostatic cancer tissues were obtained from patients undergoing prostatectomy, and rat ventral prostate was incised 3 days after castration. Forty-one AR-positive BPH specimens, 3 prostatic cancer specimens, and 6 rat prostates were used. After processing at 4 degrees C, the tissues were examined by means of high resolution isoelectric focusing (IEF) technique to determine their AR isoforms. RESULTS: From the prostatic specimens, 3 types of AR isoforms were detected with pI values at 6.5, 6.0, and 5.3. In human BPH tissues, 15/41 (36.6%) specimens showed all the three types of isoforms, while 19/41 (46.3%) showed 2 isoforms at various combinations and 7/41 (17.1%), 1 isoform. For the 3 prostatic cancer specimens, one showed 3 isoforms, one, 2 isoforms, and the other failed to show any isoform. All rat prostatic tissues showed 2 isoforms at different combinations. Binding of 3H-dihydrotestosterone (DHT) to the isoforms was inhibited by the addition of 100-fold excess of DHT or testosterone, but not progesterone, oestradiol or diethylstilboestrol. CONCLUSION: AR isoforms are different in different patients. Although their genesis is not clear, the therapeutic implication of the present observation appears to be interesting, that may help clarifying the individual differences in the response to hormonal therapy. PMID- 11202424 TI - Clinical classification of chronic prostatitis: a preliminary investigation. AB - AIM: To propose a practical clinical classification for the chronic prostatitis (CP). METHODS: The clinical features and the findings in the expressed prostatic secretion (EPS) in 804 cases of CP patients were retrospectively analyzed. RESULTS: Four types of CP were identified based on the clinical manifestations and the amounts of white blood cells (WBC) and lecithin in EPS. They were the latent type (85 cases; 10.6%), the common type (423 cases; 52.6%), the persisting type (104 cases; 12.9%), and the active type (192 cases, 23.9%). The therapeutic efficacy for these 4 subtypes were 40.4%, 76.8%, 30.8% and 37%, respectively; a statistical difference was noticed between the common type and the persisting type (P < 0.01). CONCLUSION: The method of classification proposed by the authors may help clinicians in the diagnosis and predicting the prognosis of CP. PMID- 11202425 TI - Value of herniography in the management of occult hernia and chronic groin pain in adults. PMID- 11202426 TI - Value of herniography in the management of occult hernia and chronic groin pain in adults. PMID- 11202427 TI - A problem bile duct stone. PMID- 11202428 TI - Clinical goverance and the vascular surgeon. PMID- 11202430 TI - Ribosomal proteins S3a, S13, S16, and S24 are not mutated in patients with Diamond-Blackfan anemia. PMID- 11202429 TI - Human A1 expression in acute myeloid leukemia and its relationship to Bcl-2 expression. PMID- 11202431 TI - Increased frequency of HLA-DRB1*1302 haplotype in patients with nonimmune chronic idiopathic neutropenia of adults. PMID- 11202432 TI - CD15-expressing phagocytic plasma cells in a patient with multiple myeloma. PMID- 11202433 TI - Requirement for cytoplasmic protein synthesis during circadian peaks of transcription of chloroplast-encoded genes in Chlamydomonas. AB - Cycloheximide, an inhibitor of cytoplasmic translation, induced a rapid reduction of 70-80% in levels of mRNA for the chloroplast elongation factor Tu (tufA) in asynchronously growing Chlamydomonas. This effect was shown to be mainly transcriptional, and not restricted to tufA, as transcription of other chloroplast-encoded genes were cycloheximide-sensitive, although not all equally (psbA showed no more than 40% inhibition). Confirmatory evidence that the inhibition of chloroplast transcription was mainly due to blocking cytoplasmic translation was obtained with the cycloheximide-resistant mutant act1, and by using another translation inhibitor, anisomycin. In synchronously growing Chlamydomonas, chloroplast transcription is regulated by the circadian clock, with the daily peak occurring during the early light period. When cycloheximide was added during this period, transcription was inhibited, but not when it was added during the trough period (late light to early dark). Moreover, in synchronized cells switched to continuous light, the drug blocked the scheduled increase in tufA mRNA, but did not remove the pre-existing mRNA. These experiments define two functionally different types of chloroplast transcription in Chlamydomonas, basal (cycloheximide-insensitive) and clock-induced (cycloheximide-sensitive), and indicate that the relative contribution of each type to the overall transcription of a given gene are not identical for all genes. The results also provide evidence for nuclear regulation of chloroplast transcription, thereby obviating the need for an organellar clock, at least for these rhythms. PMID- 11202434 TI - Single amino acid substitutions at the acyl-CoA-binding domain interrupt 14[C]palmitoyl-CoA binding of ACBP2, an Arabidopsis acyl-CoA-binding protein with ankyrin repeats. AB - Cytosolic acyl-CoA-binding proteins (ACBPs) are small proteins (ca. 10 kDa) that bind long-chain acyl-CoAs and are involved in the storage and intracellular transport of acyl-CoAs. Previously, we have characterized an Arabidopsis thaliana cDNA encoding a novel membrane-associated ACBP, designated ACBP1, demonstrating the existence of a new form of ACBP in plants (M.-L. Chye, Plant Mol. Biol. 38 (1998) 827-838). ACBP1 likely participates in intermembrane lipid transport from the ER to the plasma membrane, where it could maintain a membrane-associated acyl pool (Chye et al., Plant J. 18 (1999) 205-214). Here we report the isolation of cDNAs encoding ACBP2 (Mr 38,479) that shows conservation in the acyl-CoA-binding domain to previously reported ACBPs, and contains ankyrin repeats at its carboxy terminus. These repeats, which likely mediate protein-protein interactions, could constitute a potential docking site in ACBP2 for an enzyme that uses acyl-CoAs as substrate, in vitro binding assays on recombinant (His)6-ACBP2 expressed in Escherichia coli show that it binds 14[C]palmitoyl-CoA preferentially to 14[C]oleoyl-CoA. Analysis of the acyl-CoA-binding domain in ACBP2 was carried out by in vitro mutagenesis. Mutant forms of recombinant (His)6-ACBP2 with single amino acid substitutions at conserved residues within the acyl-CoA-binding domain were less effective in binding 14[C]palmitoyl-CoA. Northern blot analysis showed that the 1.6 kb ACBP2 mRNA, like that of ACBP1, is expressed in all plant organs. Analysis of the ACBP2 promoter revealed that, like the ACBP1 promoter, it lacks a TATA box suggesting the possibility of a housekeeping function for ACBP2 in plant lipid metabolism. PMID- 11202435 TI - Site-specific accumulation of a LINE-like retrotransposon in a sex chromosome of the dioecious plant Cannabis sativa. AB - Male-associated DNA sequences were analysed in hemp (Cannabis sativa L.), a dioecious plant with heteromorphic sex chromosomes. A male-associated DNA sequence in C. sativa (MADC1) and its flanking sequence encoded a reverse transcriptase that was strongly homologous to those of LINE-like retrotransposons from various plants and other organisms, as well as another open reading frame (ORF). Fluorescence in situ hybridization (FISH) with MADC1 as probe, which yielded strong signals specific for male genomic DNA in gel blot analysis, generated a clear doublet signal at the end of the long arm of the Y chromosome. FISH using pachytene chromosomes of pollen mother cells at meiotic prophase I revealed that pairing of X and Y chromosomes occurred at the short arm of the Y chromosome where MADC1 was not present. Furthermore, FISH using extended DNA fibers, with MADC1 and its flanking DNA as probes, revealed that 100 to 200 copies of the retrotransposon were located in tandem on the Y chromosome. These results support the hypothesis that accumulation of a specific LINE-like retrotransposon at the terminal region of the long arm of the Y chromosome might be one cause of heteromorphism of sex chromosomes. PMID- 11202436 TI - Molecular cloning and functional expression of a stress-induced multifunctional O methyltransferase with pinosylvin methyltransferase activity from Scots pine (Pinus sylvestris L.). AB - Formation of pinosylvin (PS) and pinosylvin 3-O-monomethyl ether (PSM), as well as the activities of stilbene synthase (STS) and S-adenosyl-1-methionine (SAM):pinosylvin O-methyltransferase (PMT), were induced strongly in needles of Scots pine seedlings upon ozone treatment, as well as in cell suspension cultures of Scots pine upon fungal elicitation. A SAM-dependent PMT protein was purified and partially characterised. A cDNA encoding PMT was isolated from an ozone induced Scots pine cDNA library. Southern blot analysis of the genomic DNA suggested the presence of a gene family. The deduced protein sequence showed the typical highly conserved regions of O-methyltransferases (OMTs), and average identities of 20-56% to known OMTs. PMT expressed in Escherichia coli corresponded to that of purified PMT (40 kDa) from pine cell cultures. The recombinant enzyme catalysed the methylation of PS, caffeic acid, caffeoyl-CoA and quercetin. Several other substances, such as astringenin, resveratrol, 5-OH ferulic acid, catechol and luteolin, were also methylated. Recombinant PMT thus had a relatively broad substrate specificity. Treatment of 7-year old Scots pine trees with ozone markedly increased the PMT mRNA level. Our results show that PMT represents a new SAM-dependent OMT for the methylation of stress-induced pinosylvin in Scots pine needles. PMID- 11202437 TI - Spatial and temporal patterns of GUS expression directed by 5' regions of the Arabidopsis thaliana farnesyl diphosphate synthase genes FPS1 and FPS2. AB - Farnesyl diphosphate synthase (FPS), the enzyme that catalyses the synthesis of farnesyl diphosphate (FPP) from isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), is considered a regulatory enzyme of plant isoprenoid biosynthesis. The promoter regions of the FPS1 and FPS2 genes controlling the expression of isoforms FPS1S and FPS2, respectively, were fused to the beta glucuronidase (GUS) reporter gene and introduced into Arabidopsis thaliana plants. The FPS1S:GUS gene is widely expressed in all plant tissues throughout development, thus supporting a role for FPS1S in the synthesis of isoprenoids serving basic plant cell functions. In contrast, the FPS2:GUS gene shows a pattern of expression restricted to specific organs at particular stages of development. The highest levels of GUS activity are detected in flowers, especially in pollen grains, from the early stages of flower development. After pollination, much lower levels of GUS activity are detected in the rest of floral organs, with the exception of the ovary valves, which remain unstained throughout flower development. GUS activity is also detected in developing and mature seeds. In roots, GUS expression is primarily detected at sites of lateral root initiation and in junctions between primary and secondary roots. No GUS activity is detected in root apical meristems. GUS expression is also observed in junctions between primary and secondary stems. Overall, the pattern of expression of FPS2:GUS suggests a role for FPS2 in the synthesis of particular isoprenoids with specialized functions. Functional FPS2 gene promoter deletion analysis in transfected protoplasts and transgenic A. thaliana plants indicate that all the cis-acting elements required to establish the full pattern of expression of the FPS2 gene are contained in a short region extending from positions -111 to +65. The potential regulatory role of specific sequences within this region is discussed. PMID- 11202438 TI - Methods of double-stranded RNA-mediated gene inactivation in Arabidopsis and their use to define an essential gene in methionine biosynthesis. AB - Controlled down-regulation of endogenous plant gene expression is a useful tool, but antisense and sense silencing lack predictability. Recent studies show that expression of both antisense and sense RNA together is an effective means of inactivating reporter and viral genes in plants. We created transgenic plants expressing antisense and sense RNA together in a single 'double-stranded RNA' (dsRNA) transcript. This approach shows great promise as a highly effective means for reducing gene function. With this approach, we demonstrated that the Arabidopsis cystathionine beta-lyase gene, which encodes a methionine biosynthetic enzyme, is essential for viability. Inactivation of this gene was rescued by the addition of methionine to the growth medium. Compared to antisense and sense constructs, the dsRNA construct showed a much more consistent and complete suppression of gene activity. Additionally, expression of a transcript with a spacer sequence containing an unrelated gene between antisense and sense luciferase gene fragments led to stronger inactivation of a second luciferase transgene than did constructs with a minimal spacing between sense and antisense fragments. However, the gene in the spacer region was neither functionally expressed nor functional in silencing a second, unlinked homologous transgene. PMID- 11202439 TI - A gene expression screen identifies EARLI1 as a novel vernalization-responsive gene in Arabidopsis thaliana. AB - Vernalization promotes early flowering in late ecotypes of Arabidopsis thaliana. The mechanisms of vernalization are poorly understood. A subtractive hybridization approach was used to isolate vernalization-responsive genes from a late-flowering ecotype of Arabidopsis thaliana based on the premise that transcript levels of such genes would increase with cold treatment and remain high even after removal of the vernalization stimulus. EARLI1 is the first Arabidopsis gene shown to be stably activated by vernalization. The abundance of its RNA is progressively elevated by vernalization and remains high for at least 20 days at room temperature. The basal level of EARLI1 RNA is higher in early flowering ecotypes, but is increased also after vernalization. Vernalization and subsequent growth in long-day photoperiods have an additive or synergistic effect on EARLI1 activation. EARLI1 RNA levels are also transiently induced by brief exposures to cold, but not to abscisic acid. EARLI1 is thus a novel vernalization responsive gene in Arabidopsis thaliana that can be used to investigate vernalization-specific transcriptional regulation. PMID- 11202440 TI - Agrobacterium-mediated sorghum transformation. AB - Agrobacterium tumefaciens was used to genetically transform sorghum. Immature embryos of a public (P898012) and a commercial line (PHI391) of sorghum were used as the target explants. The Agrobacterium strain used was LBA4404 carrying a 'Super-binary' vector with a bar gene as a selectable marker for herbicide resistance in the plant cells. A series of parameter tests was used to establish a baseline for conditions to be used in stable transformation experiments. A number of different transformation conditions were tested and a total of 131 stably transformed events were produced from 6175 embryos in these two sorghum lines. Statistical analysis showed that the source of the embryos had a very significant impact on transformation efficiency, with field-grown embryos producing a higher transformation frequency than greenhouse-grown embryos. Southern blot analysis of DNA from leaf tissues of T0 plants confirmed the integration of the T-DNA into the sorghum genome. Mendelian segregation in the T1 generation was confirmed by herbicide resistance screening. This is the first report of successful use of Agrobacterium for production of stably transformed sorghum plants. The Agrobacterium method we used yields a higher frequency of stable transformation that other methods reported previously. PMID- 11202441 TI - Promiscuous and specific phospholipid binding by domains in ZAC, a membrane associated Arabidopsis protein with an ARF GAP zinc finger and a C2 domain. AB - Arabidopsis proteins were predicted which share an 80 residue zinc finger domain known from ADP-ribosylation factor GTPase-activating proteins (ARF GAPs). One of these is a 37 kDa protein, designated ZAC, which has a novel domain structure in which the N-terminal ARF GAP domain and a C-terminal C2 domain are separated by a region without homology to other known proteins. Zac promoter/beta-glucuronidase reporter assays revealed highest expression levels in flowering tissue, rosettes and roots. ZAC protein was immuno-detected mainly in association with membranes and fractionated with Golgi and plasma membrane marker proteins. ZAC membrane association was confirmed in assays by a fusion between ZAC and the green fluorescence protein and prompted an analysis of the in vitro phospholipid binding ability of ZAC. Phospholipid dot-blot and liposome-binding assays indicated that fusion proteins containing the ZAC-C2 domain bind anionic phospholipids non-specifically, with some variance in Ca2+ and salt dependence. Similar assays demonstrated specific affinity of the ZAC N-terminal region (residues 1-174) for phosphatidylinositol 3-monophosphate (PI-3-P). Binding was dependent in part on an intact zinc finger motif, but proteins containing only the zinc finger domain (residues 1-105) did not bind PI-3-P. Recombinant ZAC possessed GTPase-activating activity on Arabidopsis ARF proteins. These data identify a novel PI-3-P-binding protein region and thereby provide evidence that this phosphoinositide is recognized as a signal in plants. A role for ZAC in the regulation of ARF-mediated vesicular transport in plants is discussed. PMID- 11202442 TI - Functional analysis of the PsbX protein by deletion of the corresponding gene in Synechocystis sp. PCC 6803. AB - The psbX gene (sml0002) coding for a 4.1 kDa protein in Photosystem II of plants and cyanobacteria was deleted in both wild type and in a Photosystem I-less mutant of the cyanobacterium Synechocystis sp. PCC 6803. Polymerase chain reaction and sequencing analysis showed that the mutants had completely segregated. Deletion of the PsbX protein does not seem to influence growth rate, electron transport or water oxidation ability. Whereas a high light induction of the psbX mRNA could be observed in wild type, deletion of the gene did not lead to high light sensibility. Light saturation measurements and 77K fluorescence measurements indicated a minor disconnection of the antenna in the deletion mutant. Furthermore, fluorescence induction measurements as well as immuno staining of the D1 protein showed that the amount of Photosystem II complexes in the mutants was reduced by 30%. Therefore, PsbX does not seem to be necessary for the Photosystem II electron transport, but directly or indirectly involved in the regulation of the amount of functionally active Photosystem II centres in Synechocystis sp. PCC 6803. PMID- 11202443 TI - 123I-IMT SPET: introducing another research tool into clinical neuro-oncology? PMID- 11202444 TI - Practice of nuclear medicine in Spain. AB - This survey presents the results of a poll sent to all Spanish nuclear medicine departments between July 1999 and March 2000, with the aim of clarifying the current situation of nuclear medicine in Spain. This survey is believed to be the first of its kind, and it is anticipated that the data will be of assistance to health authorities in ensuring that the needs of the population with regard to nuclear medicine facilities are met. PMID- 11202445 TI - Visualisation of serotonin-1A (5-HT1A) receptors in the central nervous system. AB - The 5-HT1A subtype of receptors for the neurotransmitter serotonin is predominantly located in the limbic forebrain and is involved in the modulation of emotion and the function of the hypothalamus. Since 5-HT1A receptors are implicated in the pathogenesis of anxiety, depression, hallucinogenic behaviour, motion sickness and eating disorders, they are an important target for drug therapy. Here, we review the radioligands which are available for visualisation and quantification of this important neuroreceptor in the human brain, using positron emission tomography (PET) or single-photon emission tomography (SPET). More than 20 compounds have been labelled with carbon-11 (half-life 20 min), fluorine-18 (half-life 109.8 min) or iodine-123 (half-life 13.2 h): structural analogues of the agonist, 8-OH-DPAT, structural analogues of the antagonist, WAY 100635, and apomorphines. The most successful radioligands thus far are [carbonyl 11C] WAY-100635 (WAY), [carbonyl-11C]desmethyl-WAY-100635 (DWAY), p-[18F]MPPF and [11C]robalzotan (NAD-299). The high-affinity ligands WAY and DWAY produce excellent images of 5-HT1A receptor distribution in the brain (even the raphe nuclei are visualised), but they cannot be distributed to remote facilities and they probably cannot be used to measure changes in endogenous serotonin. Binding of the moderate-affinity ligands MPPF and NAD-299 may be more sensitive to serotonin competition and MPPF can be distributed to PET centres within a flying distance of a few hours. Future research should be directed towards: (a) improvement of the metabolic stability in primates; (b) development of a fluorinated radioligand which can be produced in large quantities and (c) production of a radioiodinated or technetium-labelled ligand for SPET. PMID- 11202446 TI - SPET imaging of central muscarinic acetylcholine receptors with iodine-123 labelled E-IQNP and Z-IQNP. AB - 1-Azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha phenylacetate (IQNP) is a muscarinic acetylcholine receptor (mAChR) antagonist and the racemic ligand contains eight stereoisomers. In a single-photon emission tomography (SPET) study in monkeys we recently confirmed that [123I]E-(R,R)-IQNP ([123I]E-IQNP) is a radioligand with modest selectivity for the M1 and M4 subtypes, whereas [123I]Z-(R,R)-IQNP ([123I]Z-IQNP) is non-subtype selective. In the present SPET study, E- and Z-IQNP were examined in human subjects. SPET examination was performed on three male subjects after i.v. injection of [123I]E IQNP and in another three after i.v. injection of [123I]Z-IQNP. The binding potential (BP) for [123I]E-IQNP was calculated using several quantitative approaches with the cerebellum as a reference region. High-performance liquid chromatography was used to measure radioligand metabolism in plasma. Following [123I]E-IQNP, the radioactivity was high in the neocortex and striatum, intermediate in the thalamus and low in the pons and cerebellum, which is consistent with the rank order for the regional density of M1 and M4 subtypes in vitro. For all regions, peak equilibrium was identified within the 48-h data acquisition. The simplified reference tissue approach using SPET data from 0 to 48 h was the most reliable in this limited series of subjects. Following injection of [123I]Z-IQNP, radioactivity was high in the neocortex and striatum, intermediate in the thalamus and pons and low in the cerebellum, which is in agreement with the density of M1, M2 and M4 subtypes as measured in vitro. Quantitative analyses provided indirect support for specific M2 binding of Z-IQNP in the cerebellum. The high selectivity of [123I]E-IQNP for M1 and M4 receptors allowed the use of cerebellum as a reference region devoid of specific binding, and may be advantageous for applied clinical studies of M1 and M4 receptors binding in man. [123I]Z-IQNP has potential for exploration of M2 receptor binding in the cerebellum. PMID- 11202447 TI - Exceptional brain function in musicians and the neural basis of music processing. PMID- 11202448 TI - 123I-IMP SPET in the diagnosis of primary central nervous system lymphoma. AB - We reviewed N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) single-photon emission tomography (SPET) images of brain tumours and assessed the usefulness of 123I-IMP SPET for the diagnosis of primary central nervous system (CNS) lymphoma. We analysed 52 tumours that showed enhancement on magnetic resonance imaging: 11 malignant lymphomas, 3 anaplastic astrocytomas, 17 glioblastomas, 12 meningiomas, 4 metastatic brain tumours and 5 other brain tumours. 123I-IMP uptake in the tumours on early (15-min) and delayed (4-h) scans was visually classified as high, moderate or low as compared with the contralateral brain cortex. Early and delayed 123I-IMP uptake ratios comparing tumours with contralateral brain cortex (T/N ratio) were also calculated. In malignant lymphomas, the visual uptake of 123I-IMP was moderate to high on the delayed scans. The delayed T/N ratios were significantly higher than the early ratios (P<0.05) and all lymphomas, with the exception of one small one, had delayed ratios greater than 0.9. In non lymphomatous tumours, the visual uptake of 123I-IMP was low on the delayed scans. The delayed T/N ratios were significantly lower than the early ratios (P<0.01) and all non-lymphomatous tumours had delayed ratios of less than 0.8. The T/N ratios of lymphomas were significantly higher than those of non-lymphomatous tumours on both early and delayed scans (P<0.0001). These results suggest that 123I-IMP SPET may be a useful tool in the differential diagnosis of primary CNS lymphoma. PMID- 11202449 TI - An independent evaluation of a new method for automated interpretation of lung scintigrams using artificial neural networks. AB - The purpose of this study was to evaluate a new automated method for the interpretation of lung perfusion scintigrams using patients from a hospital other than that where the method was developed, and then to compare the performance of the technique against that of experienced physicians. A total of 1,087 scintigrams from patients with suspected pulmonary embolism comprised the training group. The test group consisted of scintigrams from 140 patients collected in a hospital different to that from which the training group had been drawn. An artificial neural network was trained using 18 automatically obtained features from each set of perfusion scintigrams. The image processing techniques included alignment to templates, construction of quotient images based on the perfusion/template images, and finally calculation of features describing segmental perfusion defects in the quotient images. The templates represented lungs of normal size and shape without any pathological changes. The performance of the neural network was compared with that of three experienced physicians who read the same test scintigrams according to the modified PIOPED criteria using, in addition to perfusion images, ventilation images when available and chest radiographs for all patients. Performances were measured as area under the receiver operating characteristic curve. The performance of the neural network evaluated in the test group was 0.88 (95% confidence limits 0.81-0.94). The performance of the three experienced experts was in the range 0.87-0.93 when using the perfusion images, chest radiographs and ventilation images when available. Perfusion scintigrams can be interpreted regarding the diagnosis of pulmonary embolism by the use of an automated method also in a hospital other than that where it was developed. The performance of this method is similar to that of experienced physicians even though the physicians, in addition to perfusion images, also had access to ventilation images for most patients and chest radiographs for all patients. These results show the high potential for the method as a clinical decision support system. PMID- 11202450 TI - Choice of collimator for cardiac SPET when resolution compensation is included in iterative reconstruction. AB - In clinical cardiac single-photon emission tomography (SPET) studies, collimators of different spatial resolution and geometric efficiency are available for imaging. In selecting the appropriate collimator for clinical use, there is a trade-off between spatial resolution, which can limit the contrast of the reconstructed image, and detection efficiency, which determines the noise in the image. Our objective was to assess which collimator is best suited for cardiac SPET when reconstruction is performed with and without compensation for distance dependent resolution (CDR). The dynamic MCAT thorax phantom was used to simulate 180 degree technetium-99m cardiac data, acquired using either a general-purpose (GP) or high-resolution (HR) collimator. For GP and HR, the resolution at 15 cm was 11.5 mm and 9.5 mm respectively, and the corresponding relative efficiency was 1.0 and 0.52 respectively. Distance-dependent resolution, attenuation and noise were included in the projection data; scatter was not included. Ordered subsets expectation maximisation reconstruction (subset size 4) was performed with and without CDR. Results were evaluated by comparing the myocardial recovery coefficient and contrast between myocardium and ventricle relative to the original phantom, each plotted for different noise levels corresponding to increasing iteration number. The study demonstrated that, without CDR, HR gave the best results. However, for any given noise level with CDR, GP gave superior recovery and contrast. These findings were confirmed in a physical phantom study. Results suggest that improved reconstruction can be achieved using a GP collimator in combination with resolution compensation. PMID- 11202451 TI - Elastic surface contour detection for the measurement of ejection fraction in myocardial perfusion SPET. AB - The aim of this study was to investigate the use of an automated three dimensional myocardial contour detection method using elastic surfaces for the assessment of left ventricular ejection fraction (EF) from electrocardiographically (ECG) triggered myocardial perfusion single-photon emission tomography (SPET). The validity of this method was studied on the basis of both phantom measurements and patient studies. Phantom measurements were performed using an elastic phantom of the left ventricle simulating a beating heart, with a simulated EF ranging from 10% to 78%. The data from 27 patients who had undergone both ECG-triggered myocardial perfusion SPET and planar gated radionuclide ventriculography (RNV) were used to compare the EF derived from the SPET data with the automated contour detection method and the EF derived from the RNV data with standard analysis software. EF values as measured by RNV ranged from 11% to 68%. The overall accuracy of the automated contour detection method proved to be very high. In the phantom study the deviation of the measured EF from the reference values was less than 4% for all of the simulated EFs. The studies on the patient data yielded a correlation coefficient (Pearson) greater than 0.94 as compared with planar RNV. Intra- and inter-observer reproducibility was high, with correlation coefficients exceeding 0.97. It is concluded that the proposed method allows accurate, reproducible and fast measurement of the left ventricular EF on the basis of myocardial perfusion SPET. PMID- 11202452 TI - Imaging in vivo herpes simplex virus thymidine kinase gene transfer to tumour bearing rodents using positron emission tomography and. AB - Radiolabelled ganciclovir analogues have shown promise as imaging agents to detect herpes simplex virus thymidine kinase (HSVtk) expression. This study evaluated the use of positron emission tomography (PET) imaging with 9-[(3 [18F]fluoro-1-hydroxy-2-propoxy)methyl]guanine ([18F]FHPG) to assess gene transfer into tumours. HSVtk-positive and HSVtk-negative cell lines were first treated in vitro with [18F]FHPG. To assess the efficacy of PET in detecting HSVtk expression following in vivo gene transfer, mice were injected intravenously with an adenovirus encoding HSVtk (Ad.HSVtk), a control vector (Ad.Bgl2) or saline. Subcutaneous human glioma xenografts were grown in mice and treated by direct injection of Ad.HSVtk or Ad.Bgl2. Imaging was performed 48 h after transduction. Similar experiments were performed using Fischer rats implanted with syngeneic tumours. The presence of the HSVtk protein was confirmed by immunohistochemistry. Biodistribution studies were also obtained in 14 naive mice. In vitro studies showed high and specific uptake of [18F]FHPG in HSVtk-positive cell lines, with an uptake ratio of up to 27:1. PET imaging and direct counting of major organs demonstrated HSVtk-specific tracer retention. In mice, HSVtk-positive tumours retained 3.4% dose/gram as compared to 0.6% for control tumours (P=0.03). They were clearly seen on the PET images as early as 100 min post injection. Similar results were obtained with syngeneic rat tumours. Biodistribution studies demonstrated the rapid distribution and clearance of the tracer in all major organs. Our results demonstrate that PET imaging of HSVtk gene transfer to tumours is feasible and is highly specific for HSVtk expression. PMID- 11202453 TI - Scintimammography with 99mTc-MIBI versus dynamic MRI for non-invasive characterization of breast masses. AB - Although mammography remains the technique of choice for the early detection of breast cancer, several imaging techniques, including scintimammography and magnetic resonance imaging (MRI), have recently been proposed as adjuncts for this purpose and included in many diagnostic protocols. This study was undertaken to assess the clinical accuracy of scintimammography with technetium-99m methoxyisobutylisonitrile (MIBI) and contrast-enhanced MRI in the detection of primary breast carcinoma in patients with equivocal mammographic findings. Forty nine patients with a suspicious breast mass detected either by physical examination or by mammography and ultrasound (US) were studied. All patients underwent scintimammography and dynamic contrast-enhanced MRI 1 week apart. The results of the two techniques were compared and correlated to the final diagnoses. Two independent readers reported the scans using a four-point confidence scale. The areas under the receiver operator characteristic (ROC) curves were obtained. Scintimammography showed an accuracy for tumour detection of 84%, with a sensitivity of 80% and a specificity of 88%. MRI showed an accuracy of 86%, with a sensitivity and specificity of 96% and 75%, respectively. Comparison of the two areas under the ROC curves showed no significant differences between MRI, 0.91+/-0.05 (mean+/-SD), and scintimammography, 0.88+/ 0.05 (P=0.9). It is concluded that dynamic MRI and scintimammography possess comparable accuracy in the diagnosis of primary breast carcinoma in patients with equivocal mammographic or US findings. PMID- 11202454 TI - 18F-DOPA positron emission tomography for tumour detection in patients with medullary thyroid carcinoma and elevated calcitonin levels. AB - In spite of the availability of numerous procedures, diagnostic imaging of tumour manifestations in patients with medullary thyroid carcinoma and elevated calcitonin levels is often difficult. In the present study, the new procedure of fluorine-18 dihydroxyphenylalanine positron emission tomography (18F-DOPA PET) was compared with the established functional and morphological imaging methods. After evaluation of the normal distribution of 18F-DOPA, 11 patients with medullary thyroid carcinoma were examined using 18F-DOPA PET. Results of 18F fluorodeoxyglucose (18F-FDG) PET, somatostatin receptor scintigraphy (SRS) and morphological tomographic imaging (CT/MRI) were available for all patients. All individual procedures were evaluated without reference to prior information. Data assessment for each patient was based on cooperation between experienced radiologists and specialists in nuclear medicine, who considered all the available findings (histological results, imaging, follow-up studies). This cooperation served as the gold standard against which the results of the individual procedures were evaluated. A total of 27 tumours were studied [three primary tumours (PT)/local recurrence (LR), 16 lymph node metastases (LNM) and eight organ metastases (OM)]. 18F-DOPA PET produced 17 true-positive findings (2 PT/LR, 14 LNM, 1 OM), 18F-FDG PET 12 (2 PT/LR, 7 LNM, 3 OM), SRS 14 (2 PT/LR, 8 LNM, 4 OM) and morphological imaging 22 (3 PT/LR, 11 LNM, 8 OM). The following sensitivities were calculated with respect to total tumour manifestations: 18F DOPA PET 63%, 18F-FDG PET 44%, SRS 52%, morphological imaging 81%. Thus, the morphological imaging procedures produce the best overall sensitivity, but the specificity for PT/LR (55%) and LNM (57%) was low. With respect to lymph node staging, the best results were obtained with 18F-DOPA PET. 18F-DOPA PET is a new functional imaging procedure for medullary thyroid carcinoma that seems to provide better results than SRS and 18F-FDG PET. Moreover, the data indicate that no single procedure provides adequate diagnostic certainty. Therefore, 18F-DOPA PET is a useful supplement to morphological diagnostic imaging, improving lymph node staging and enabling a more specific diagnosis of primary tumour and local recurrence. PMID- 11202456 TI - Characteristics of a new fully programmable blood sampling device for monitoring blood radioactivity during PET. AB - The first performance tests of a new fully programmable blood sampling device for monitoring blood radioactivity during positron emission tomography (PET) are described. Blood is withdrawn through 1-mm internal diameter tubing using an infusion pump which can be operated at rates varying from 0 to 600 ml/h. Activity in blood is measured by a 6-cm-thick bismuth germanate crystal connected to a photomultiplier tube and multichannel analyser (MCA) which are positioned within 6 cm lead shielding. Positioning of the tubing is an exact and simple procedure. The minimal readout time of the MCA is 1 s. Two independent energy windows can be set. Operation of the pump and MCA is fully controlled by a PC, i.e. sampling time, interval time and pump rate can be varied at any time during the PET scan by user-defined scripts. A number of characteristics of the new system were studied, such as sensitivity, dead time, linearity, effect of background radiation and pump rate as a function of input pressure. In addition, dispersion was measured as a function of pump rate. Finally, first clinical results were compared with manual samples. The sensitivity equalled 0.7 and 0.2 cps/Bq for 511 and 1022-keV 30% energy windows, respectively, and the system dead time was 500 ns. The system remained linear within 2% with activity concentrations up to 2.5 MBq/cc. Short-term reproducibility was better than 3% for a 1-h period. Long-term reproducibility was about 5% (ISD), which was mainly caused by variation in the diameter of the tubing. If the device was positioned in such a way that maximum shielding was directed towards the patient, the effects of background radiation from the patient on the measured activity concentration for clinically relevant conditions was minimal (<3%). Pump rate varied with input pressure, but remained constant for a given pressure. Dispersion constants smaller than 0.14 s(-1) were observed for pump rates higher than 300 ml/h, indicating that the system dispersion is small. Clinical data showed an excellent agreement to within 3% (ISD) between the results obtained with the new system and manual samples. With the continuous blood sampler radioactivity in blood can be measured accurately during the entire course of the PET scan. Furthermore, the system is fully programmable allowing adjustment of all parameters during a single PET scan. PMID- 11202455 TI - Activation of the growth plates on three-phase bone scintigraphy: the explanation for the overgrowth of fractured femurs. AB - Children with an uncomplicated femoral fracture, treated with superimposition of fragments and intentional shortening, usually develop overgrowth of the fractured femur and the ipsilateral tibia which may compensate for the initial shortening and enable the limb in question to reach a length similar to that on the normal side. The overgrowth is evaluated clinically and by scanography. The increased metabolic activity of the growth plates that support this overgrowth has not been documented by any laboratory method. In order to evaluate the metabolic activity of the growth plates, 18 patients (11 males, seven females; mean age 6.1 years) with fractures of the femur were studied at three different time intervals (2-5 months, 6-12 months and 18-24 months). Three-phase bone scintigraphy was performed in all patients. Ten children (five males, five females; mean age 7.5 years) who had had bone imaging for other reasons were used as the control group. Visual analysis of the flow and equilibrium phases was performed for the distal femoral and proximal tibial growth plates. Visual and semi-quantitative analyses of the delayed images were performed for the distal femoral and proximal and distal tibial growth plates. Semi-quantitative analyses yielded the following activity ratios: (a) the distal femoral growth plate of the fractured femur to the contralateral one (FR); (b) the proximal growth plate of the tibia on the side of the fractured femur to the contralateral one (TpR); (c) the distal growth plate of the tibia on the side of the fractured femur to the contralateral one (TdR); and (d) in the control group, the distal growth plates of both femora (FCG) and the proximal (TCGp) and distal (TCGd) growth plates of the tibiae. Visual analysis of the blood flow, equilibrium and delayed images showed increased activity in the distal femoral growth plates during the first and second time intervals, but not during the third. No significant activity changes were found in the proximal and distal tibial growth plates during any of the phases analysed. The mean and standard deviation for FR in the three time intervals were: FRI=1.22+/-0.27, FRII=1.17+/-0.16 and FRIII=1.09+/-0.20. FR values were significantly higher than in the control group (FCG=0.99+/-0.03) (P=0.033). The mean and standard deviation for TpR in the three time intervals were: TpRI=1.08+/-0.18, TpRII=0.94+/-0.09 and TpRIII=0.96+/-0.20. TpR values were not significantly different from those in the control group (TCGp=1.00+/-0.05). However, TpRI was significantly higher than TpRII (P=0.043). The mean and standard deviation for TdR in the three time intervals were: TdRI=1.10+/-0.41, TdRII=1.05+/-0.15 and TdRIII=1.13+/-0.36. TdR values were not significantly higher than in the control group (TCGd=1.00+/-0.04) (P=0.777). These results support the concept that three-phase bone imaging is able to quantify and determine that activation occurs in the distal femoral and proximal tibial growth plates of fractured femora. This phenomenon may explain the overgrowth observed in this injured bone structure. PMID- 11202457 TI - Non-uniform versus uniform attenuation correction in brain perfusion SPET of healthy volunteers. AB - Although non-uniform attenuation correction (NUAC) can supply more accurate absolute quantification, it is not entirely clear whether NUAC provides clear-cut benefits in the routine clinical practice of brain SPET imaging. The aim of this study was to compare the effect of NUAC versus uniform attenuation correction (UAC) on volume of interest (VOI)-based semi-quantification of a large age- and gender-stratified brain perfusion normal database. Eighty-nine healthy volunteers (46 females and 43 males, aged 20-81 years) underwent standardised high resolution single-photon emission tomography (SPET) with 925 MBq 99mTc-ethyl cysteinate dimer (ECD) on a Toshiba GCA-9300A camera with 153Gd or 99mTc transmission CT scanning. Emission images were reconstructed by filtered back projection and scatter corrected using the triple-energy window correction method. Both non-uniform Chang attenuation correction (one iteration) and uniform Sorenson correction (attenuation coefficient 0.09 cm(-1)) were applied. Images were automatically reoriented to a stereotactic template on which 35 predefined VOIs were defined for semi-quantification (normalisation on total VOI counts). Small but significant differences between relative VOI uptake values for NUAC versus UAC in the infratentorial region were found. VOI standard deviations were significantly smaller for UAC, 4.5% (range 2.6-7.5), than for NUAC, 5.0% (2.3 9.0) (P<0.01). Higher filter roll-off values of the transmission reconstruction filter increased noise in the emission images and altered estimated cortical attenuation coefficients as well as uptake values. In conclusion, semi quantification based upon reconstruction with UAC results in very similar 99mTc ECD uptake values in healthy volunteers to those obtained with NUAC, although values for the infratentorial region are slightly lower. NUAC produces a slight increase in inter-subject variability. Further study is necessary in various patient populations to establish the full clinical impact of NUAC in brain perfusion SPET. PMID- 11202458 TI - 62Cu-PTSM and PET used for the assessment of angiotensin II-induced blood flow changes in patients with colorectal liver metastases. AB - The aim of this study was to establish a quantitative positron emission tomography (PET) method for investigating angiotensin II (AII)-induced changes in blood flow distribution in the liver. This was in order to evaluate the role of vascular manipulation applied to locoregional chemotherapy treatment in patients with colorectal liver metastases. The tracer selected was copper-62 (II) pyruvaldehyde bis-(N4-methyl)thiosemicarbazone (62Cu-PTSM), which exhibits high first-pass extraction and tissue retention following intra-arterial administration. The short half-life of the tracer and its availability from a 62Zn/62Cu generator enabled short-interval repeat PET scans on patients in a single imaging session. Distribution of tracer within the liver was imaged in a single view using a PET camera with rotating large-area detectors. By optimisation of the acquisition protocol, it was possible to acquire sufficient data to produce good-quality images and to quantify tracer uptake with an accuracy of <10%. Reproducibility of the imaging method was assessed in a single patient in whom three consecutive 62Cu-PTSM PET scans were obtained, and in whom no vascular manipulation was performed. Sets of scans (before, during and immediately after a 45-min AII infusion) were obtained in nine patients to assess blood flow changes associated with prolonged vascular manipulation. Significant individual responses, varying in both the magnitude and the duration of flow change, were observed in the majority of cases (7/11 lesions; 7/9 patients). These findings illustrate the potential of 62Cu-PTSM and PET for pharmacological studies. The wide range of individual patient responses to AII infusion suggests that PET blood flow assessment would be of value for selecting patients in whom this procedure may be effective. PMID- 11202459 TI - End-stage glaucoma: fortunately the end may be far off. PMID- 11202460 TI - Corneal allograft rejection: has the time come for intravenous pulsed methylprednisolone? A debate. PMID- 11202461 TI - Management and prognosis of end-stage glaucoma. AB - PURPOSE: We followed, for a long term, end-stage glaucoma patients as defined by the level of legal blindness. METHODS: Follow up was for 7.7+/-1.8 years (range 2 9) for 22 patients (13 men and nine women) having 32 eyes with functional vision. Age at exit was 74.6+/-15.5 years (range 33-89). Humphrey computerized perimetry and applanation tonometry were used throughout. We attempted to hold intraocular pressure below 15 mmHg using as much medical therapy as required. RESULTS: All visual fields were less than 10 degrees diameter at exit, but at entry seven eyes of six patients still had a field between 10 degrees and 20 degrees, the rest were all less than 10 degrees. Corrected visual acuity at entry was 6/9 to 6/6 in 21 eyes of 6 patients and none had less than 6/60. At exit 16 eyes had 6/9 to 6/6 and five eyes had less than 6/60, but no patient had complete loss of vision. Mean intraocular pressure (IOP) throughout was below 15 mmHg in all but four patients, whose (IOP) were less than 20 mmHg, using multiple medications if necessary. All patients had undergone prior surgery and/or laser trabeculoplasty. CONCLUSIONS: Even though visual loss slowly progressed, most patients with end stage glaucoma retained functional vision for a long period when intraocular pressure was held below 15 mmHg. More stringent early control of intraocular pressure may avoid the development of end-stage glaucoma. PMID- 11202462 TI - Iodine-I25 episcleral plaque therapy in uveal melanoma. AB - PURPOSE: To assess the efficacy of iodine-125 (I-125) episcleral plaque therapy in the management of uveal melanoma with regard to local control, survival, globe preservation and visual outcome. METHODS: Between January 1985 and January 1997, 50 patients with the diagnosis of uveal melanoma were treated with I-125 episcleral plaques. The mean initial tumour height was 5.5 mm (range, 2.0-9.5 mm) and basal diameter 9.5 mm (range, 4.0-14.5 mm). I-125 seeds with a mean activity of 1259.1 MBq were used. The mean apical dose was 80.5 Gy (range, 68.0-95.0 Gy). Scleral dose ranged from 225.0 to 940.0 Gy. Pretreatment visual acuity was 6/60 or better in 43 patients. RESULTS: One patient was lost to follow up and excluded from analysis. The remaining 49 patients had a mean follow up of 39.5 months. There were seven local failures, with a mean duration to tumour progression of 16.7 months. All seven patients were successfully managed with enucleation. Five other enucleations were performed for treatment-related complications. At the time of analysis, 10 patients have died, five of metastatic melanoma. Of the patients with preserved globes, corrected visual acuity was 6/60 or better in 31 patients. CONCLUSIONS: Good local tumour control and survival can be achieved with episcleral plaque therapy. Globe preservation with useful vision was possible in the majority of cases. Our findings are in keeping with other reported series. PMID- 11202463 TI - Potential acuity meter results in cataract patients. AB - PURPOSE: To determine the ability of the potential acuity meter (PAM) to predict potential visual acuity through lenticular opacities in a group of cataract patients without significant other ocular pathology. METHODS: This prospective study undertook PAM measurements on each eye of 84 subjects during preoperative hospital visits to either A Scan or Primary Care clinics. PAM results were compared to best corrected visual acuity findings obtained at least 6 weeks post cataract extraction. RESULTS: Comparison of PAM result to visual outcome showed poor correlation (rho = 0.41, P = 0.0005). Using predictive estimates, 49% of subjects' PAM results underestimated visual outcome as determined by a difference of greater than 2 Snellen acuity lines in these results. Factors such as preoperative vision level, cataract type and pupil dilation did not significantly influence the predictive power of the PAM. Preoperative pinhole results were also correlated with visual outcome (rho = 0.42, P = 0.0006). Vison in the fellow eye of subjects with 6/9 or better was correlated to the PAM result indicating a moderate to good predictive power in 'normal' eyes. CONCLUSIONS: PAM results were considered to be poor for a clinical test. The results of this study indicate that this instrument has only a limited usefulness as part of the standard preoperatve examination in patients undergoing cataract extraction. PMID- 11202464 TI - Warfarin therapy and cataract surgery. AB - PURPOSE: Cataract extraction in the warfarinized patient poses special considerations. Warfarin will increase the haemorrhagic risk but, more importantly, cessation or reduction in anticoagulation may well lead to serious thromboembolic phenomena. The purpose of this study was to assess the impact that warfarinization has on cataract extraction. METHODS: One thousand consecutive cataract extractions performed at Christchurch Hospital between 1996 and 1998 were reviewed. Twenty-eight patients (29 eyes) were on warfarin. Reasons for anticoagulation, modification to treatment regimen and postoperative outcome measures were available for 23 eyes or 79% of the study population. RESULTS: The preoperative international normalized ratio (INR) ranged from 1.00 to 2.40+/-0.37 with a mean of 1.52. No thromboembolic phenomena occurred and four minor perioperative haemorrhages were noted, none of which affected the final visual outcome. CONCLUSIONS: If warfarin is required to counteract serious thromboembolic tendencies, then it should not be ceased perioperatively. The small numbers of perioperative haemorrhages that did occur were not visually significant. PMID- 11202465 TI - Intraretinal axon diameters of a New World primate, the marmoset (Callithrix jacchus). AB - PURPOSE: Previously, measurements of retinal ganglion cell axon diameter have been used to make inferences about the physiology and clinical pathology of the visual pathway. However, few of these studies were able to unequivocally relate axon diameter to retinal ganglion cell type and other associated measurements. In this and our previous study we have examined intraretinal axon diameters to determine if differences in axon diameter may help to explain conduction velocity measurements found previously. METHODS: Individual retinal ganglion cells of a New World primate, the common marmoset (Collithrix jacchus) were injected iontophoretically with 2% Lucifer yellow and 4% neurobiotin. Labelled cells were visualized by horseradish peroxidase immunohistochemistry and diaminobenzidine and then retinae were mounted vitreal side up on a glass slide. Cell measurements were made with the aid of a camera lucida attachment and computer-aided morphometry Axons were photographed under x 100 oil immersion and measured at a final magnification of x 4600. RESULTS: A sample of 62 parasol cells, 22 midget cells, 16 hedge cells and 11 small bistratified cells were analysed. Dendritic field diameter of the different cell classes showed only moderate (non significant) increases with eccentricity. Only the parasol cells demonstrated a significant increase in mean axon diameter with eccentricity. When the parasol class was examined more closely, it was found that only parasol cells of the superior, inferior and temporal retina (SIT group) showed significant positive correlations between different cell parameters (mean axon diameter, soma diameter, dendritic field diameter, eccentricity). Soma and dendritic field diameters of the SIT group were significantly larger than those of the nasal parasol cells. However, mean axon diameters of the SIT cells were not significantly different from nasal parasol cells. Axon diameters of nasal parasol cells were very variable and overlapped those of the midget and hedge cell classes to a large extent. CONCLUSIONS: The present data show that for marmoset parasol cells there may not be a clearly defined distinction between nasal and superior, inferior and temporal parasol cells on the basis of axon size. Of particular interest in the present analysis is the clear separation of superior, inferior and temporal parasol cells and nasal parasol cells when comparing soma and dendritic field diameters which is not reflected in the distribution of axon diameters. We suggest that changes in diameter along the length of an axon, differences between retinal quadrants and the variability between cells may be related to minimization of spatiotemporal dispersion necessary for accurate perception of motion within the visual world. PMID- 11202466 TI - Acute haemorrhagic keratoconjunctivitis following laser in situ keratomileusis. AB - We report two cases of acute haemorrhagic keratoconjunctivitis which occurred following laser in situ keratomileusis (LASIK) during an ongoing epidemic. Both cases underwent preoperative investigation and surgery on the same day. The possible sources of contamination include the paramedical staff, the contact instruments used for performing preoperative investigation, surgeon, nurse, surgical instruments and eye drops. However, the flap was intact with no haze or regression and at 1 year follow up, the visual acuity was maintained at 6/6 in both the patients. We recommend greater caution while performing contact investigations and strict surgical asepsis during LASIK surgery, routinely as well as during epidemics of conjunctivitis. PMID- 11202467 TI - Coexistent adenoviral keratoconjunctivitis and Acanthamoeba keratitis. AB - A 17-year-old youth presented with bilateral follicular conjunctivitis and nummular subepithelial corneal infiltrates. Failure of this to settle in an outpatient setting led to corneal scraping with microscopy and culturing for bacteria, fungi, Herpes simplex, adenovirus and Acanthamoeba as an inpatient. Polymerase chain reaction analysis of corneal cells was positive for adenovirus, and culture on live Escherichia coli-coated agar plates was positive for Acanthamoeba by phase contrast microscopy on day two. We conclude that Acanthomoeba infection can complicate adenoviral keratoconjunctivitis. This observation is in keeping with previously reported modes of infection by Acanthamoeba, whereby any epithelial breach seems to allow inoculation of the eye by this opportunistic organism. PMID- 11202468 TI - Cyanoacrylate glue for corneal perforations: a description of a surgical technique and a review of the literature. AB - The effective early application of a cyanoacrylate glue corneal patch can aid in the management of small corneal perforations, corneal melts and wound leaks. Their use gives improved visual outcomes with reduced enucleation rates (6% vs 19%). It may also avoid the need for tectonic penetrating keratoplasty. Cyanoacrylate glue prevents re-epithelialization into the zone of damaged and naked stroma and prevents the development of the critical setting for collagenase production that leads to stromal melting. Cyanoacrylates also have significant bacteriostatic activity against gram-positive organisms. We describe a simple and easily reproducible method of cyanoacrylate corneal patch application, with neglible risk of inadvertent glue complications. It has the further advantage of a smooth corneal surface rather than an irregular surface as often occurs with direct application methods. With corneal application, the major concern is toxicity of cyanoacrylates through direct contact with the corneal endothelium and lens. Fibrin glues may be less toxic; however, they are not as readily available. The longer alkyl chains of currently available cyanoacrylate glues (e.g. Histoacryl) slows degradation significantly, limiting accumulation of histotoxic by-products to amounts that can be effectively eliminated by tissues. Vigilance in monitoring for infection/corneal infiltrate is necessary at all times, especially when the glue has been present for more than 6 weeks. Corneal patching with cyanoacrylate glue is a temporizing procedure only, buying time to allow healing secondary to medical treatment of the underlying condition, or allowing surgery to be elective and under more optimal conditions once inflammation has been reduced and the integrity of the globe restored. PMID- 11202469 TI - Family ties. PMID- 11202470 TI - A horrible system for everybody. PMID- 11202471 TI - Tobacco cessation. PMID- 11202472 TI - The Langston collection. PMID- 11202473 TI - Introduction to symposium: clinical and molecular insights from uncommon lung diseases. PMID- 11202475 TI - Lymphangioleiomyomatosis. AB - Lymphangioleiomyomatosis (LAM), a rare disorder of unknown cause that occurs almost exclusively in women of childbearing years, is characterized microscopically by abnormal smooth muscle proliferation in the lung, lymphatics, and mediastinal, abdominal and lower cervical lymph nodes. LAM is associated with progressive dyspnea, recurrent pneumothoraces, chylous effusions, abdominal tumors (angiomyolipoma), and chylous ascites. Because of the predilection of this disease for young women, therapies to date have mainly involved hormonal manipulation. Although the efficacy of these therapies has not been established, the clinical course is more favorable in recent studies compared with earlier reports. PMID- 11202474 TI - Polymorphisms in candidate asthma genes. AB - The triad of reversible airway obstruction, bronchial hyperresponsiveness, and airway inflammation characterizes asthma. The etiology of asthma is complex and involves the interaction of multiple genetic foci and a variety of environmental factors, such as protein allergens, chemical sensitizers, and viral or bacterial proteins. Candidate asthma genes have been identified that may be linked or associated with the asthmatic phenotype. Potential candidate asthma genes include cytokine genes, receptor genes, transcription factors, immune recognition genes, and genes regulating lipid mediator generation. Although polymorphisms within either the promoter or coding region of individual asthma candidate genes have been identified, the association between these genetic polymorphisms and the asthmatic phenotype remains incompletely defined. Furthermore, genetic polymorphisms mediating the asthmatic phenotype are rarely identified in individual patients. This manuscript reviews several of the specific mutations and polymorphisms that have been identified in candidate asthma genes, such as the high affinity IgE receptor, the beta2-adrenergic receptor, the interleukin-4 promoter and receptor, the tumor necrosis factor gene, and the 5-lipoxygenase promoter. PMID- 11202476 TI - Surfactant protein B deficiency: insights into surfactant function through clinical surfactant protein deficiency. AB - Surfactant protein B (SP-B) deficiency is a disorder of surfactant function with complete or transient absence of SP-B in term neonates. SP-B, 1 of 4 described surfactant-associated proteins, plays a key role in surfactant metabolism, particularly in intracellular packaging of surfactant components, formation of tubular myelin, and the presentation of the surfactant phospholipid monolayer to the air-fluid interface within the alveolus. Neonates with clinical SP-B deficiency best demonstrate the key role of SP-B in surfactant function. "Classic" deficiency results in severe respiratory failure in term infants and death unless lung transplantation is performed. Because the initial description of complete deficiency secondary to a homozygous frameshift mutation in codon 121 of the SP-B cDNA, partial deficiencies with differing genetic backgrounds and less severe clinical courses have been reported. These partial deficiency states may provide a clearer picture of genotype/phenotype relationships in SP-B function and surfactant metabolism. SP-B deficiency or dysfunction may be more common than once thought and may play a significant role in neonatal lung disease. PMID- 11202477 TI - Disorders of ciliary motility. AB - Clearance of mucus and other debris from the airways is achieved by 3 main mechanisms: mucociliary activity, coughing, and alveolar clearance. Disorders of ciliary structure or function results in impaired clearance, and result in chronic sinopulmonary disease manifested as chronic sinusitis, otitis media, nasal polyposis, and ultimately bronchiectasis. In addition, situs inversus, dextrocardia, and infertility can be associated with dysfunctional ciliary activity. The term primary ciliary dyskinesia has been proposed for the spectrum of these diseases. The term Kartagener syndrome applies to this syndrome when accompanied by infertility and dextrocardia or situs inversus. The more common types of ciliary dysmotility syndromes are characterized by missing dynein arms, central microtubule pairs, inner sheath, radial spokes, or nexin links. In addition to structural defects within the cilia, disordered ciliary beating and disordered ciliary arrays on epithelial cell surfaces have been described in this syndrome. Treatment includes rigorous lung physiotherapy, prophylactic and organism-specific antibiotics, and immunization against common pulmonary pathogens. Late stages of the disease may require surgical intervention for bronchiectasis or lung transplant for end-stage lung disease. PMID- 11202478 TI - Alpha1-antitrypsin deficiency: biological answers to clinical questions. AB - Alpha1-antitrypsin (alpha1AT) deficiency is a common lethal hereditary disorder of white persons of European descent. The condition is characterized by reduced serum levels of alpha1AT, a 52-kDa glycoprotein synthesized chiefly in the liver and, to a lesser extent, by macrophages and neutrophils. Alpha1AT acts as an antiprotease and is the physiological inhibitor of neutrophil serine proteases such as neutrophil elastase cathepsin G and proteinase 3. The clinical manifestations of alpha1AT deficiency occur chiefly in the lung, with a high risk of emphysema occurring by the third or fourth decade of life. Cigarette smoking accelerates the development of emphysema in persons with alpha1AT deficiency. There is also an increased risk of liver disease in alpha1AT deficiency, which occurs mostly in childhood. In this review, we will define further the diagnosis of alpha1AT deficiency and its clinical manifestations and describe the therapeutic strategies that are currently being developed to treat the hepatic and pulmonary disease associated with this condition. PMID- 11202479 TI - Common variable immunodeficiency. AB - Common variable immunodeficiency (CVI) is a heterogeneous immunodeficiency syndrome characterized by hypogammaglobulinemia, recurrent bacterial infections, and a variety of immunological abnormalities. In addition to recurrent infections, patients with this syndrome also suffer from an increased incidence of autoimmune disease and malignancy. Because the spectrum of associated diseases is broad, patients with CVI are seen by a variety of medical specialists. In this review, the pathogenesis, clinical manifestations, diagnosis, and treatment of CVI are discussed. PMID- 11202480 TI - Nontuberculous mycobacteria. AB - The nontuberculous mycobacteria are for the most part ubiquitous environmental organisms that only rarely cause disease in humans. Therefore, the normal host defense against these organisms must be quite robust, as exposure is universal and disease is rare. The organisms that are most commonly encountered in clinical practice, Mycobacterium avium, M. intracellulare, M. kansasii, M. fortuitum, M. abscessus, and M. chelonae, are frequently found in water sources and soil. These organisms share significant structural and biochemical similarities with their more pathogenic relative, M. tuberculosis (MTB). Because they are of significantly lower pathogenicity than MTB, patients with abnormal susceptibility to these infections should include those with defects that may be identifiable. Study of these patients should lead to determination of the mechanisms underlying resistance to these organisms, which in turn are likely to be highly informative regarding host defense against these infections and their more virulent relative MTB. Furthermore, recognition of host factors that permit infection with nontuberculous mycobacteria in otherwise normal hosts will identify pathways that can be targeted for therapeutic intervention. Thus, the search for genetic and acquired susceptibility to nontuberculous mycobacteria is also a search for susceptibility factors for MTB as well as an opportunity to recognize endogenous pathways that can be exploited therapeutically. PMID- 11202481 TI - Pneumocystis carinii pneumonia in patients without HIV infection. AB - Pneumocystis carinii is an important, but sporadic, opportunistic pulmonary pathogen in immunosuppressed HIV seronegative persons. Historically, patients at highest risk for P. carinii pneumonia are included infants with severe malnutrition, children with primary immunodeficiencies, patients with hematological malignancies, and recipients of solid organ or bone marrow transplants. Recently, solid tumor patients, in particular those receiving high dose corticosteroids for brain neoplasms, and patients with inflammatory or collagen-vascular disorders, especially patients with Wegener granulomatosis receiving immunosuppressive therapy, have been identified as subgroups at increased risk for P. carinii pneumonia. Other factors associated with P. carinii pneumonia include the intensity of the immunosuppressive regimen and tapering doses of corticosteroids. Because P. carinii pneumonia is associated with significant morbidity and mortality, it is important to identify high-risk patient populations to administer effective chemoprophylactic agents, such as trimethoprim-sulfamethoxazole. PMID- 11202482 TI - Erdheim-Chester disease: a rare multisystem histiocytic disorder associated with interstitial lung disease. AB - Erdheim-Chester disease (ECD) is a rare multisystem histiocytosis syndrome of unknown cause that usually affects adults. Histiocytic infiltration of multiple end organs produces bone pain, xanthelasma and xanthoma, exophthalmos, diabetes insipidus, and interstitial lung disease. Differential diagnosis includes Langerhans cell histiocytosis, metabolic disorders, malignancy, and sarcoidosis. ECD can be diagnosed using a combination of clinical and histopathologic findings. Sites of involvement include lung, bone, skin, retroorbital tissue, central nervous system, pituitary gland, retroperitoneum, and pericardium. Symmetrical long bone pain with associated osteosclerotic lesions, xanthomas around the eyelids, exophthalmos, and/or diabetes insipidus suggest ECD. Approximately 35% of patients have associated lung involvement, characterized by interstitial accumulations of histiocytic cells and fibrosis in a predominantly perilymphangitic and subpleural pattern. This pattern distinguishes ECD from other histiocytic disorders involving the lung. The diagnosis is confirmed by tissue biopsies that contain histiocytes with non-Langerhans cell features. In general, the clinical course of patients with this disease varies, and the prognosis can be poor despite treatment. Clinical trials for treatment of ECD have not been conducted and treatment is based on anecdotal experience. PMID- 11202483 TI - Wegener granulomatosis. AB - Wegener granulomatosis (WG) is a necrotizing, granulomatous vasculitis that has a clinical predilection to involve the upper airways, lungs, and kidneys. Although the first case was reported by Klinger in 1931, Friedrich Wegener in 1936 characterized the unique clinical and pathological features of this disease that subsequently came to bear his name. Vascular inflammation and occlusion leading to tissue ischemia is a hallmark of WG. Although strong evidence indicates that such blood vessel damage is immunologically mediated, the mechanisms that initiate this process are still largely unknown. To date, there has been no clearly established association with genetic factors, specific infectious agents, or environmental irritants, although speculation has remained that these may play a role in triggering the onset of disease. Until the introduction of therapy with cyclophosphamide (CYC) and glucocorticoids, WG was uniformly fatal. Although drug toxicity and disease relapse remain of concern with this regimen, it has provided us with a successful means of treatment and the opportunity to better understand this disease through long-term patient follow-up. PMID- 11202484 TI - Potential pathogenesis and clinical aspects of pulmonary fibrosis associated with rheumatoid arthritis. AB - Pulmonary fibrosis is an extra-articular disorder that can occur in association with rheumatoid arthritis. The differential diagnosis of this disorder is similar to that of idiopathic pulmonary fibrosis, but specific entities such as atypical pulmonary infections and drug-induced interstitial lung disease must be considered as causes of pulmonary fibrosis in patients with rheumatoid arthritis. Although the cause of lung fibrosis in persons with rheumatoid arthritis is unknown, factors that can potentially contribute to the pathogenesis of this pulmonary disease include genetic susceptibility, development of an altered immunologic response, and/or aberrant host repair processes. The clinical course of patients with pulmonary fibrosis and rheumatoid arthritis is heterogeneous but is generally insidious, chronic, and progressive. These patients respond unpredictably to available empiric therapeutic agents and, overall, their prognosis is poor; limited data suggests that the median survival time can be less than 4 years. PMID- 11202485 TI - Beryllium disease. AB - Berylliosis is an environmental chronic inflammatory disorder of the lung caused by inhalation of insoluble beryllium (Be) dusts and characterized by the accumulation of CD4+ T cells and macrophages in the lower respiratory tract. In response to Be inhalation, noncaseating granuloma formation and, eventually, fibrosis. The immunopathogenic process is maintained by Be-specific lung CD4+ T lymphocytes. Consistent with the disease immunopathology, these Be-specific T cells have a T-helper 1 phenotype producing interleukin-2 and interferon-gamma, the macrophage-activating cytokine driving the granulomatous reaction. Previous studies have demonstrated that the glutamic acid in position 69 of the human leukocyte antigen class II b chain is strongly associated with increased susceptibility to Be in exposed workers, suggesting that human leukocyte antigen gene markers may be used as epidemiological probes to identify population groups at higher risk. PMID- 11202486 TI - Clinical insights and basic science correlates in sarcoidosis. AB - More than a century has elapsed since the initial description of sarcoidosis, but critical aspects of the disorder remain poorly understood. Information obtained from epidemiologic observations and basic laboratory research suggests that the disease may represent an immunologic response to an exogenous agent in a genetically susceptible individual. However, a definitive etiologic role for any specific exogenous agent has never been proved, and a "candidate gene" underlying a predisposition to sarcoidosis has not yet been identified. This review presents an historical framework for considering available evidence regarding a transmissible agent in sarcoidosis and host susceptibility to the disease. PMID- 11202487 TI - William James and the unconscious: redressing a century-old misunderstanding. AB - Contrary to received wisdom in psychology, William James did not oppose postulating unconscious processes. This mistaken belief stems from a misreading of a passage in his Principles concerned with disproving the metaphysical notion that mental states are composed of elementary mental units. The term unconscious had been co-opted by individuals who supported this position. Unconscious did not mean then what it means now. Analysis of the rest of the Principles, his later works, and his reactions to the works of others reveals that James actually supported what we would now term unconscious processes. He even contributed to their study with his notions of the "fringe," "habit," and "subconscious incubation." Causes and effects of this misunderstanding are discussed. PMID- 11202488 TI - Contrasts and correlations in effect-size estimation. AB - This article describes procedures for presenting standardized measures of effect size when contrasts are used to ask focused questions of data. The simplest contrasts consist of comparisons of two samples (e.g., based on the independent t statistic). Useful effect-size indices in this situation are members of the g family (e.g., Hedges's g and Cohen's d) and the Pearson r. We review expressions for calculating these measures and for transforming them back and forth, and describe how to adjust formulas for obtaining g or d from t, or r from g, when the sample sizes are unequal. The real-life implications of d or g calculated from t become problematic when there are more than two groups, but the correlational approach is adaptable and interpretable, although more complex than in the case of two groups. We describe a family of four conceptually related correlation indices: the alerting correlation, the contrast correlation, the effect-size correlation, and the BESD (binomial effect-size display) correlation. These last three correlations are identical in the simple setting of only two groups, but differ when there are more than two groups. PMID- 11202489 TI - Amnesia is a deficit in relational memory. AB - Eye movements were monitored to assess memory for scenes indirectly (implicitly). Two eye movement-based memory phenomena were observed: (a) the repetition effect, a decrease in sampling of previously viewed scenes compared with new scenes, reflecting memory for those scenes, and (b) the relational manipulation effect, an increase in viewing of the regions where manipulations of relations among scene elements had occurred. In normal control subjects, the relational manipulation effect was expressed only in the absence of explicit awareness of the scene manipulations. Thus, memory representations of scenes contain information about relations among elements of the scenes, at least some of which is not accessible to verbal report. But amnesic patients with severe memory impairment failed to show the relational manipulation effect. Their failure to show any demonstrable memory for relations among the constituent elements of scenes suggests that amnesia involves a fundamental deficit in relational (declarative) memory processing. PMID- 11202490 TI - Subliminal mere exposure: specific, general, and diffuse effects. AB - The present research examined the possibility that repeated exposure may simultaneously produce specific and diffuse effects. In Study 1, participants were presented with 5-ms exposures of 25 stimuli each shown once (single-exposure condition) or with five repetitions of 5 stimuli (repeated-exposure condition). Participants in the repeated-exposure condition subsequently rated their own mood more positively than those in the single-exposure condition. Study 2 examined whether affect generated by subliminal repeated exposures transfers to unrelated stimuli. After a subliminal exposure phase, affective reactions to previously exposed stimuli, to new but similar stimuli, and to stimuli from a different category were obtained. Previously exposed stimuli were rated most positively and novel different stimuli least positively. All stimuli were rated more positively in the repeated-exposure condition than in the single-exposure condition. These findings suggest that affect generated by subliminal repeated exposure is sufficiently diffuse to influence ratings of unrelated stimuli and mood. PMID- 11202491 TI - Interactions between visual working memory and selective attention. AB - The relationship between working memory and selective attention has traditionally been discussed as operating in one direction: Attention filters incoming information, allowing only relevant information into short-term processing stores. This study tested the prediction that the contents of visual working memory also influence the guidance of selective attention. Participants held a sample object in working memory on each trial. Two objects, one matching the sample and the other novel, were then presented simultaneously. As measured by a probe task, attention shifted to the object matching the sample. This effect generalized across object type, attentional-probe task, and working memory task. In contrast, a matched task with no memory requirement showed the opposite pattern, demonstrating that this effect is not simply due to exposure to the sample. These results confirm a specific prediction about the influence of working memory contents on the guidance of attention. PMID- 11202492 TI - Sex differences in mathematical reasoning ability at age 13: their status 20 years later. AB - Reported is the 20-year follow-up of 1,975 mathematically gifted adolescents (top 1%) whose assessments at age 12 to 14 revealed robust gender differences in mathematical reasoning ability. Both sexes became exceptional achievers and perceived themselves as such; they reported uniformly high levels of degree attainment and satisfaction with both their career direction and their overall success. The earlier sex differences in mathematical reasoning ability did predict differential educational and occupational outcomes. The observed differences also appeared to be a function of sex differences in preferences for (a) inorganic versus organic disciplines and (b) a career-focused versus more balanced life. Because profile differences in abilities and preferences are longitudinally stable, males probably will remain more represented in some disciplines, whereas females are likely to remain more represented in others. These data have policy implications for higher education and the world of work. PMID- 11202493 TI - Group discussion as interactive dialogue or as serial monologue: the influence of group size. AB - Current models draw a broad distinction between communication as dialogue and communication as monologue. The two kinds of models have different implications for who influences whom in a group discussion. If the discussion is like interactive dialogue, group members should be influenced most by those with whom they interact in the discussion; if it is like serial monologue, they should be influenced most by the dominant speaker. The experiments reported here show that in small, 5-person groups, the communication is like dialogue and members are influenced most by those with whom they interact in the discussion. However, in large, 10-person groups, the communication is like monologue and members are influenced most by the dominant speaker. The difference in mode of communication is explained in terms of how speakers in the two sizes of groups design their utterances for different audiences. PMID- 11202494 TI - Genetic and environmental contributions to loneliness in children. AB - This report presents the results of the first behavioral genetic studies of children's loneliness. Data were collected using both an adoption design and a twin-sibling design. As part of the Colorado Adoption Project, 133 sibling pairs (69 biologically related pairs and 64 unrelated pairs in adoptive families) completed a general loneliness scale when they were 9, 10, 11, and 12 years old. As part of the San Diego Sibling Study, 142 sibling pairs (22 monozygotic twin, 40 dizygotic twin, and 80 full-sibling pairs) between the ages of 8 and 14 years old completed a scale assessing loneliness at school. Both studies showed significant heritability and nonshared environmental influences for children's loneliness. PMID- 11202495 TI - Revisiting the perception of upside-down faces. AB - In two experiments, the effect of orientation on face perception was assessed. Using a scale from 1 (normal) to 7 (bizarre), participants rated normal, unaltered faces and faces in which changes had been made to spatial-relational properties (eyes and mouth inverted or relative position of the eyes and mouth altered) or to component properties (eyes whitened and teeth blackened). For unaltered and component-distortion faces, bizarreness ratings increased linearly as orientation increased from 0 degree to 180 degrees. For spatial-distortion faces, a discontinuity in the function relating orientation and bizarreness was in evidence between 90 degrees and 120 degrees. The results provide support for the view that there is a qualitative difference in the processing of upright and inverted faces due to the disproportionate effect of inversion on the encoding of spatial-relational information. PMID- 11202496 TI - How special are objects? Children's reasoning about objects, parts, and holes. AB - Discrete physical objects have a special status in cognitive and linguistic development. Infants track and enumerate objects, young children are biased to construe novel words as referring to objects, and, when asked to count an array of items, preschool children tend to count the discrete objects, even if explicitly asked to do otherwise. We address here the question of whether discrete physical objects are the only entities that have this special status, or whether other individuals are salient as well. In two experiments, we found that 3-year-olds are just as good at identifying, tracking, and counting certain nonobject entities (holes in Experiment 1; holes and parts in Experiment 2) as they are with objects. These results are discussed in light of different theories of the nature and development of children's object bias. PMID- 11202497 TI - The integrity of Web-delivered experiments: can you trust the data? AB - Data from Web-delivered experiments conducted in browsers by remote users of PsychExperiments, a public on-line psychology laboratory, reveal experiment effects that mirror lab-based findings, even for experiments that require nearly millisecond accuracy of displays and responses. Textbook results are obtained not just for within-subjects effects, but for between-subjects effects as well. These results suggest that existing technology is adequate to permit Web delivery of many cognitive and social psychological experiments and that the added noise created by having participants in different settings using different computers is easily compensated for by the sample sizes achievable with Web delivery. PMID- 11202498 TI - Negotiating false memories: interviewer and rememberer characteristics relate to memory distortion. AB - In a recent study, more than half of the participants were led to create a partial or complete false memory for an emotional childhood event (e.g., serious animal attack). Using a subsample from that study, we examined the hypothesis that memory distortion is related to characteristics of interviewers and rememberers. The relations between susceptibility to memory distortion and (a) dissociation (Dissociative Experiences Scale) and (b) personality traits (NEO Five Factor Inventory) were investigated. Results indicated that participants who exhibited memory distortion scored significantly higher on the dissociative scale than their counterparts who did not exhibit memory distortion. Further, susceptibility to memory distortion was associated with higher extraversion scores in interviewers and lower extraversion scores in participants. This pattern of findings suggests that false memories may derive from a social negotiation between particular interviewers and rememberers. PMID- 11202499 TI - Now you see it, now you don't: explicit versus implicit measures of the personal/group discrimination discrepancy. AB - When making explicit self-report ratings, members of status- and racial-minority groups report less personal experience with discrimination than that encountered by their group--a phenomenon called the personal/group discrimination discrepancy (PGDD). This study provides evidence, for the first time, that the PGDD may be, in part, a product of the procedure used to measure it. White women and men completed explicit and implicit measures of personal and group discrimination based on sex. The PGDD surfaced among women in the explicit measures, but not in the implicit measures. These findings suggest that explicit and implicit measures might provide different assessments of experience with discrimination. PMID- 11202500 TI - Social dominance orientation and group context in implicit group prejudice. AB - We tested the joint influence of individual difference and situational factors on implicit group prejudice. Participants in Experiments 1 and 2 were briefly shown in-group or out-group pronouns prior to evaluating good or bad trait adjectives. Under standard conditions (Experiment 1), there was no difference between participants with high and low social dominance orientation (SDO), but when the intergroup context was made more salient (Experiment 2), high-SDO participants alone showed implicit group prejudice. Implications for the malleability and consensuality of implicit prejudice are discussed. PMID- 11202501 TI - [Psychotropic effect of the Astragalus mongolicus preparation]. AB - Study of the pharmacological properties of a preparation from the plants of Mongolian milk vetch (Astragalus mongolicus) of the Leguminosae Juss. family showed evidence of a pronounced psychotropic activity. The main action components are the anxiolytic (tranquilizer), antidepressant, antiamnesic, and antiaggressive effects. PMID- 11202503 TI - [Comparative characteristics of cerebrovascular protective effects of mildronate, riboxine, and their combination during modeling of cerebral hemodynamics disturbance]. AB - Hydrogen clearance, polarographic, and electric impedance measurements on conscious rabbits with electrodes implanted into brain cortex, thalamus, and hypothalamus were used to study the state of hemodynamics, oxygen and water- electrolyte balance on a model of the zero-gravity-induced cerebrovascular disorders. The preliminary administration of mildronate (10 mg/kg, p.o.) reduced the hemodynamics disorder and optimized the oxygen balance more significantly than did riboxin (5 mg/kg). Both drugs markedly decreased the level of edematous phenomena in the brain. The antihypoxant and antiedematous effects of mildronate and riboxin increased upon their combined administration. PMID- 11202502 TI - [Characteristics of effects of acetylene amino alcohols M-cholinoreceptor blockers on the dopaminergic system in Daphnia magna]. AB - Haloperidol and dimethpromide exhibit the properties of dopamine antagonists in the experiments on Daphnia magna Straus (Crustaceae family). Haloperidol, in contrast to dimethpromide, does not significantly influence the toxic effect of apomorphine. It is suggested that acetylene aminoalcohol derivatives are selective ligands for one of the subtypes of dopamine receptors. PMID- 11202504 TI - [Effect of the sympathetic nervous system activation on the antifibrillatory efficacy of various anti-arrhythmia agents]. AB - Experiments with a 7-min occlusion followed by reperfusion of the left coronary artery in narcotized rats showed that antiarrhythmic drugs of various classes- ethacizin (class I), AL-275 (class III), and CM-345 (class V)--produce pronounced antifibrillatory and antiarrhythmic effects. AL-275 and CM-345, in contrast to ethacizin, retained their efficacy under the conditions of isoproterenol-induced stimulation of beta-adrenoceptors. This difference in behavior is probably explained by dissimilar effects of the antiarrhythmics on the ion channels of cardiomyocite membranes. PMID- 11202505 TI - [Anti-arrhythmic effect of the sigma-receptor blocker DuP 734 in ischemia and myocardial reperfusion]. AB - It has been found that in vivo pretreatment of rats with the sigma receptor antagonist DuP 734 (1 mg/kg) resulted in an increase in the heart tolerance to ischemic and reperfusion arrhythmias both in vivo and ex vivo. Administration of DuP 734 (1 mg/liter) directly in the perfusion solution of isolated rat heart 10 min before total ischemia also promoted a decrease in the incidence of reperfusion arrhythmias. The normoxic perfusion of isolated rat heart at a dose of 1 mg/liter had no effect on the action potential. It was concluded that antiarrhythmic effect of DuP 734 might depend on the decrease in the Ca2+ overload but not on K+ and Na+ channel blockade. PMID- 11202506 TI - [Effects of verapamil and gynipral on the uterine contractile activity in rats]. AB - Verapamil and gynipral administered to pregnant rats in doses on a clinical level suppress the uterine contractions, which is manifested by a decrease in the amplitude and frequency of the biopotential. The joint administration of gynipral and verapamil (in half doses) resulted in a pronounced tocolytic effect. PMID- 11202507 TI - [Comparative study of the NMDA-blocking activity and safety of mono- and bis cationic compounds in animals]. AB - Experiments on intact mice and rats showed that the monoammonium adamantyl containing compounds memantine, amantadine, and IEM-1958 (an N-propyl amantadine analog) are capable of blocking the NMDA receptors and producing the anticonvulsant and antihypoxant effects in the case of a systemic administration in doses close to toxic. The acute toxicity of these compounds upon intraperitoneal injections to mice is manifested in doses only 2-8 times the minimum effective dose level. The bis-cationic compounds (arcaine, IEM-1464, and IEM 1490) containing two identical cation groups, exhibit a more pronounced activity and higher safety as compared to those of their monocationic counterparts. This is explained by the ability of the bis-cationic compounds to block a polyamine site of the NMDA receptor. Arcaine (the polyamine site blocker) and IEM-1464 produce the NMDA-receptor-blocking effect and exhibit the anticonvulsant and antihypoxant activity in doses 5-10 times smaller as compared to the effective dose of memantine. At the same time, arcaine is 5 times less toxic than memantine. The bis-adamantyl derivative IEM-13490 is 100-150 times more active and has a 139 times greater therapeutic ratio than memantine. PMID- 11202508 TI - [Effect of chronic epaden administration on the tissue plasminogen activator activity in rabbits]. AB - The chronic oral administration of epaden (a concentrate of n-3 polyunsaturated fatty acids, n-3 PUFA) to rabbits leads to a decrease in activity of the tissue type plasminogen activator (t-PA) in the blood plasma. In order to elucidate the mechanism of this phenomenon, the epinephrine (adrenaline) stimulated t-PA release in rabbits pretreated with epaden for 4 weeks was compared to that in the control (untreated) group. The epinephrine injections led to a reliable, albeit short-time, increase in the t-PA activity in both test and control groups. Although the base activity of t-PA in the epaden-treated group was lower than that in the control group, the t-PA release in the former group was more pronounced. In addition, the t-PA production was induced by the immobilization shock model in rabbits one month after beginning of the epaden administration (animals in the control group were subject to the shock without epaden pretreatment). In this test, the t-PA release was also more intense in the epaden treated animals. These results indicate that the dietary epaden administration per os reduces the basal t-PA level, but increases the agonist-induced plasminogen activator production. PMID- 11202509 TI - [Hemostimulant effect of pantohematogen in myelosuppression induced by cytostatics]. AB - Pantohematogen stimulates hemopoiesis in mice with cyclophosphane induced bone marrow hypoplasia. The hemopoiesis recovery activated by pantohematogen is manifested by the granulocyte lineage hyperplasia in the bone marrow, rapid restoration of the polymorphonuclear leukocyte and monocyte counts in the peripheral blood, and the development of neutrophilia and monocytosis. The activation effect of pantohematogen on the bone marrow hemopoiesis is related to stimulating the precursor cell proliferation and differentiation and to increasing the functional activity of the hemopoietic microenvironment. PMID- 11202510 TI - [Ultrastructural changes in the pancreas of rats with acute pancreatitis after semax administration]. AB - Semax favorably affects ultrastructural changes in the pancreas of rats with acute pancreatitis (AP): a single introduction of semax (0.1 mg/kg) into the pancreatic duct of rats with AP model prevents increased necrosis of the acinar tissues and inhibits purulent inflammation of the necrotised lobules by inducing their sclerosis and atrophy, thus retaining large areas of the pancreas intact. PMID- 11202511 TI - [Comparative study of dimephosphon and xidiphone efficacy in steroid-induced osteoporosis in rats]. AB - The efficacy of dimephosphon in comparison with xydiphone was studied in rats with an osteoporosis model induced by prednisolone administration at a daily dose of 50 mg/kg over a period of 14 days. The prednisolone treatment led to an increase in the content of oxyproline (a marker of bone resorption), calcium, and inorganic phosphates in the urine. Dimephosphon (monophosphate) decreased the levels of oxyproline, calcium, and inorganic phosphate in the urine. Xydiphone (biphosphonate) equally reduced the oxyproline excretion and the calcium level in urine, while rather insignificantly affecting the phosphaturia. Dimephosphon normalized the blood calcium level, while xydiphone decreased this parameter. An additional advantage of dimephosphon over xydiphone was manifested by normalization of the body weight of test rats and the total blood protein level. PMID- 11202512 TI - [Potential role of the antimutagenic effect of xymedone in modification of immunoreactivity]. AB - Effects of the pyrimidine derivatives of xymedone and methyluracil upon the induction of point mutations of the base pair substitution type in the Salmonella/microsome test and the frequency of chromosome aberrations in the lymphocytes of patients with the chronic osteomyelitis diagnosis. Xymedone more effectively than methyluracil inhibited the induction of point mutations by nitrosomethylurea. In the case of the cyclophosphane induced mutagenesis, the two preparations exhibited comparable antimutagen effects. Both xymedone and methyluracil (1.5 g/day, 10 days) reduced the (increased) frequency of chromosomal aberrations in the lymphocytes of patients with the chronic osteomyelitis diagnosis. The anticlastogenic effect of methyluracil vanished 5 days after termination of the 10-day administration course, while xymedone exhibited an afteraction anticlastogenic effect over this period. Interrelation of the antimutagen effect and immunomodulating activity of xymedone is discussed. PMID- 11202513 TI - [Anti-inflammatory effect of fensulkal]. AB - Experiments on various animals showed that fensulkal, a new phenylglyoxylic acid derivative, possesses a high antiinflammatory activity and low toxicity, markedly exceeding butadion in the therapeutic index. The mechanism of the antiphlogistic effect of fensulkal is due to its antagonism with respect to mediators of the inflammatory process and the ability of suppressing the increased permeability of capillaries and is partly related to the adrenal cortex. The drug is registered and recommended for application as antiinflammatory remedy in the form of ointment to be used for the treatment of some gynecological disorders. PMID- 11202514 TI - [Acute toxicity of bemithyl and bromithyl]. AB - The experiments on rats showed for bemithyl LD50 = 581.48 (350.17-965.57) mg/kg and for bromithyl LD50 = 1750.30 (1463.07-2093.92) mg/kg (males) and 1584.29 (1280.46-1960.22) mg/kg (females). The therapeutic ratios are 4-6 for both drugs, while the toxicity index is 10-15 for bemithyl and 20 <196> 22 for bromithyl. It was established that ergotropic effects prevail in the toxicity of bemithyl administered in the 20-80 mg/kg dose range, while trophotropic effects are dominating at doses above 100 mg/kg. Bromithyl exhibits a dose-dependent trophotropic effect in the entire dose range. PMID- 11202515 TI - [Effect of antioxidants on endotoxicosis in experimental peritonitis]. AB - The chronic experiments on dogs with a peritonitis model showed that drugs possessing antioxidant properties (vitamin E, dimephosphon, xymedone) are capable of decreasing the inflammatory phenomena in abdominal cavity and decreasing the expression of endogenous intoxication, as manifested by a decrease in the plasma toxicity and the content of average-molecular-weight peptides and lipid peroxidation products. The most pronounced positive effect was observed for xymedone. A certain correlation between the effects of antioxidants upon endotoxicosis and free-radical lipid peroxidation reactions was established. This result suggests the therapeutic effect of antioxidants used for the treatment of peritonitis is related to their membrane-stabilizing ability. PMID- 11202516 TI - [Morphological estimation of apoptosis in preclinical studies of new drugs]. AB - A method for morphological estimation of the thymus cell loss during apoptosis proposed, which can be used as a screening test in the stage of preclinical characterization of new biologically active compounds. Efficacy of the proposed method is demonstrated by evaluating the degree of apoptosis-inducing effect of some antitumor preparations. PMID- 11202518 TI - [Chronopharmacology of cardiovascular drugs]. PMID- 11202517 TI - [Measurement of the transcapillary fluid exchange in anesthesized rats]. AB - An experimental model was developed for the study of antiedemic drug activity in anesthetized rats. The effect of furosemide upon the transcapillary fluid shift was studied. It is shown that the character of changes in the arterio-venous difference of blood density in response to postural (orthostatic versus antiorthostatic) changes can be used to udge on the filtration and reabsorption processes in the microcirculation bed of hind extremities in anesthetized rats. PMID- 11202519 TI - [Importance of adenosine A2A receptors in resistance to complete global cerebral ischemia]. AB - Selective A2A agonists (CGS 21680 and DPMA) produce a moderate neuroprotector effect with respect to the complete global cerebral ischemia (GCI). At the same time, selective A2A antagonists 8-(3-chlorostyrylcaffeine (CSC) and ZM 241385 somewhat reduce the brain resistance to complete GCI, completely prevent the neuroprotector effect of CGS 21680, partly suppress the neuroprotector activity of adenosine and 5'-N-ethylcarboxamidoadenosine (NECA), and do not affect (CSC) or potentiate (ZM 241385) the neuroprotector effect of N6-cyclopentyladenosine. The A2A-receptors are probably mediating in the neuroprotector activity of CGS 21680 and participating in the natural brain stability with respect to complete GCI, as well as in the effects of NECA and adenosine. PMID- 11202520 TI - Hard to swallow. The high cost of direct-to-consumer advertising. PMID- 11202522 TI - Drug rep advice raises gift ethics concerns. PMID- 11202521 TI - Closing the door on sample closets. PMID- 11202523 TI - Drug prices. In search of a fix. PMID- 11202524 TI - The Minnesota Medical Association's resolutions on pharmaceutical policy. PMID- 11202525 TI - Maine Rx: the act to establish fairer prescription drug prices. PMID- 11202526 TI - The MMA's 2001 legislative preview. PMID- 11202527 TI - A focus on pharmacy. PMID- 11202528 TI - Genome holds key to preventive medicine. PMID- 11202529 TI - Consumers use error rates to judge health care quality, survey shows. PMID- 11202530 TI - USP issues first report from medication-errors database. PMID- 11202531 TI - Internet use affects health care decision-making, survey confirms. PMID- 11202532 TI - Pharmacist shortage identified by government. PMID- 11202533 TI - Revising a policy on inline filtration. PMID- 11202534 TI - Pygeum. PMID- 11202535 TI - Projecting future drug expenditures--2001. AB - Drug cost projections for 2001 and factors that are likely to influence drug costs are discussed. The year 2000 introduced many new factors into the decision making process for drug pricing and raised new considerations regarding drug therapy, distribution, and costs. It is anticipated that drug costs will continue to increase at a rate of 11-15% in 2001. Research and development expenditures for new drugs continue to grow and are estimated to be $26.4 billion in 2000, but the number of new drug approvals, especially for new entities, has not increased significantly. The generic drug industry has been expanding, and sales of generics are expected to increase to $20 billion by 2005. Drug costs also keep rising, and sales may reach $243 billion by 2008; this amounts to 12.6% of total health care spending, compared with 8.1% in 1999. There is a trend toward increasing the rate of conversion of prescription drugs to nonprescription status; this may reduce drug budgets somewhat. 2001 will see new systems of drug distribution and pricing, a federal prospective pricing system for ambulatory care patients covered by Medicare, drug imports from foreign manufacturers, and states taking legal action to reduce prescription drug costs. Drug costs in 2001 are expected to continue to increase at double-digit rates. The increase in costs is due to increased utilization, to new products replacing older products, and to price increases for drugs currently on the market. PMID- 11202536 TI - Regulation of the compounding of positron emission tomography drugs. AB - Controversial aspects of the regulatory framework for compounding drug products used in positron emission tomography (PET) are discussed. The Food and Drug Administration Modernization Act of 1997 (FDAMA), which amends the Federal Food, Drug, and Cosmetic Act (FFDCA), required that FDA establish approval (new drug application [NDA] and abbreviated new drug application [ANDA]) procedures and current good manufacturing practice (CGMP) requirements for PET drugs; this seems to conflict with differentiation between manufacturing and compounding in FFDCA. Compounding by pharmacists is implied in the FDAMA section on PET, but specific mention of "pharmacist" needs to be included. Congress apparently did not intend for compounded PET drugs to be regulated differently from other drugs. Although FDA has waived NDA and ANDA fees for three PET radiopharmaceuticals, revision of FDAMA to exempt PET drug products from regulations placed on manufacturing is needed. Without relief from the current regulations, many academic PET centers are likely to close; this would violate FDAMA's stated intent of making PET available to patients at reasonable cost. Also problematic is FDAMA's prohibition of compounding "regularly or in inordinate amounts" a product that is commercially available; the common PET radiopharmaceutical fludeoxyglucose F 18 injection, for example, is commercially available. A sensible alternative to NDA or ANDA and CGMP requirements would be the enforcement of USP standards for PET drugs by state boards of pharmacy. PMID- 11202537 TI - Current role of beta-adrenergic blockers in the treatment of chronic congestive heart failure. AB - Recent findings on the use of beta-adrenergic blockers in patients with congestive heart failure (CHF) are reviewed. CHF is a progressive, debilitating disease that afflicts 4.6 million patients in the United States. Treatment has traditionally consisted of a diuretic, an angiotensin-converting-enzyme (ACE) inhibitor, and digoxin. Despite advances in ACE-inhibitor therapy, the five-year mortality rate remains nearly 50%. Overstimulation of the sympathetic nervous system is believed to contribute to mortality. Beta-blockers have recently been added to the standard of care for patients with New York Heart Association functional class II or III heart failure. Four randomized, double-blind, placebo controlled clinical trials were recently completed that addressed the benefits of beta-blockers in CHF. The overall mortality rate was reduced 65% by carvedilol, 34% by metoprolol, and 33% by bisoprolol; all these reductions were significant compared with placebo, and the trials were ended early. Bucindolol, however, did not have a significant effect on mortality. These drugs are hepatically metabolized and may require dosage adjustment in hepatically impaired patients. Decompensation of heart failure is another consideration; a beta-blocker should be added only for patients with stable CHF. Dosages must be slowly adjusted to targeted levels. Adverse effects do not differ significantly among beta-blockers. In addition to their effect on mortality, beta-blockers reduce CHF-related morbidity, such as all-cause hospitalization. Carvedilol, metoprolol, and bisoprolol decrease the mortality and morbidity associated with CHF and can be used with limited adverse effects. The choice among these agents does not affect clinical outcomes; bucindolol, however, has proven ineffective. PMID- 11202538 TI - Beyond pharmaceutical manufacturer assistance: broadening the scope of an indigent drug program. AB - A medication assistance program at a university medical center is described. The program was implemented in July 1999 by the ambulatory care pharmacy at the University of Illinois at Chicago Medical Center (UICMC). A full-time pharmacist and a full-time social worker run the program, along with support from technicians and a student extern. The program functions like a clinic, with both scheduled appointments and drop-ins. Patients are referred by UICMC providers or may self-refer. Sources of assistance include Medicaid, Medicare Part B, several state programs, manufacturers' programs, drug samples, private insurance plans and HMOs, and the patients themselves in the form of small payments. Patients receive medications at UICMC's expense only as a last resort. The medication assistance program helped 231 patients in the six months from July to December 1999. Program costs totaled $110,537, but $237,985 was saved. Only 13% of the savings came from pharmaceutical companies; 63% came from Medicaid. Experience with the program suggests that medication assistance initiatives should be structured to tap the full spectrum of resources for indigent patients, that programs be staffed by personnel with relevant experience, that program staff be prepared to work closely with patients and to follow up, and that the institution's charitable goods and services be restricted to patients for whom there are no other resources. A highly proactive medication assistance program at a university medical center improves the access of indigent patients to medications and is cost-effective. PMID- 11202539 TI - Health care costs associated with escalation of drug treatment in type 2 diabetes mellitus. AB - The cost of different intensities of therapy in HMO patients with type 2 diabetes mellitus was studied. Health care utilization data from 1995 were obtained for 12,200 registrants from the Kaiser Permanente Northwest Diabetes Registry who had type 2 diabetes mellitus. The data were used to determine costs associated with the escalation of antidiabetic therapies in persons with type 2 diabetes mellitus. The total annual costs (in 1993 dollars) associated with no drug therapy, a sulfonylurea only, metformin, a sulfonylurea plus insulin, and insulin alone were $4400, $4187, $4838, $8856, and $7365, respectively. Per patient total costs were higher for patients who had received antidiabetic therapy in 1995 or previously than for those who had not ($5303 versus $4365) and for patients who had received insulin therapy than for those who had not ($7379 versus $4117). Macrovascular complications accounted for 62-89% of the cost associated with inpatient treatment of diabetes-related complications. The total cost of treating patients with type 2 diabetes mellitus at an HMO increased as antidiabetic therapies escalated. PMID- 11202540 TI - Tracking pharmacist interventions with a hand-held computer. PMID- 11202541 TI - Pharmaceutical manufacturer assistance programs for indigent patients: solution or symptom? PMID- 11202542 TI - Reimbursement for pharmacists' cognitive services in the inpatient setting. PMID- 11202543 TI - Focus group on telepharmacy. AB - The focus group strongly believed that telepharmacy will change the practice of pharmacy and that it is not a matter of if or when but how. Consumers' expectations and the need for efficient health care delivery will drive the use of technology. Pharmacists have considerable lever-age in this technological world because of the money associated with the use of medications. Telepharmacy holds great promise for the profession and should result in greater visibility of pharmacists and enhanced patient access to their services. PMID- 11202544 TI - The paratesticular region: histoanatomic and general considerations. AB - The paratesticular region includes the testicular collecting system, the testicular tunics, and spermatic cord. For the purpose of discussion in this issue, the rete testis is also considered part of the paratestis, although it is principally intratesticular in location. The embryologic origins of the paratesticular components and their detailed anatomic and histologic features are presented to provide a background to better understand the pathologic processes affecting the paratestis. A wide variety of cysts, hyperplasias, neoplasms, and tumor-like conditions may affect the paratesticular region, at times resulting in challenging problems in differential diagnosis. An approach to the paratesticular causes of an intrascrotal mass lesion is presented. PMID- 11202545 TI - Cysts and epithelial proliferations of the testicular collecting system (including rete testis). AB - Neoplastic and non-neoplastic proliferations of the testicular collecting system may be a source of diagnostic difficulty as they are rarely encountered and may have an appearance that leads to confusion with lesions arising in adjacent structures. The rete testis and epididymis are the 2 sites that are most likely to give rise to this unusual group of lesions. This article principally, although not exclusively, deals with those lesions that produce an intrascrotal mass. These include benign acquired or developmental cysts such as cystic dysgenesis of the rete testis or acquired cystic transformation of the rete testis, non neoplastic epithelial proliferations such as adenomatous hyperplasia of the rete testis or cribriform hyperplasia of the epididymis, and benign or malignant neoplasms. Rete testis cystadenoma, including the sertoliform variant, and papillary cystadenoma of the epididymis are examples of benign tumors of the testicular collecting system that must be considered, the latter is the more likely of the 2 to be encountered. Primary carcinoma of either the rete testis or the epididymis is a rare occurrence; these entities are considered in some detail to allow for their recognition and distinction from other tumors that may occur in this region. Our own experience with 18 unpublished cases of lesions of the rete is also present. PMID- 11202546 TI - Mesothelial lesions of the paratesticular region. AB - Mesothelial lesions involving the paratesticular region include mesothelial cysts, reactive mesothelial hyperplasia, adenomatoid tumors, benign cystic mesothelioma, well-differentiated papillary mesothelioma, and malignant mesothelioma. The diagnosis and management of these lesions are often difficult for surgical pathologists, surgeons, and oncologists alike. Mesothelial lesions are relatively uncommon and most benign and malignant tumors present as testicular tumors with no specific findings. A preoperative diagnosis of malignancy is rarely made, and there is no established effective therapy for malignant mesothelioma. This article reviews the clinicopathologic features of paratesticular mesothelial lesions with emphasis in their differential diagnosis and prognosis. PMID- 11202547 TI - Paratesticular soft tissue neoplasms. AB - Paratesticular soft tissue tumors are uncommon neoplasms that may present significant challenges for the pathologist and clinician. This article reviews the incidence of these rare tumors, and on the common benign and malignant entities that occur in this location. Key points in differential diagnosis are emphasized. The grading, staging, and management of patients with paratesticular sarcomas is also discussed. PMID- 11202548 TI - Miscellaneous rare paratesticular tumors. AB - A few uncommon but distinctive tumors may preferentially involve the paratestis. The 3 unusual tumors that represent the focus of this discussion are the ovarian type epithelial tumors (OTET), the desmoplastic small round cell tumor (DSRCT), and the melanotic neuroectodermal tumor of infancy (MNTI). The OTETs are testicular homologues of their more common namesake counterparts that arise in the ovary. Most frequent of these are serous tumors of borderline malignancy, with fewer cases of serous carcinomas or other forms of mullerian differentiation. DSRCT is an increasingly recognized, aggressive, "small blue cell" neoplasm with distinctive clinical and pathologic features. These polyphenotypic tumors characteristically, but not invariably, arise in intimate association with the serosal membrane of the peritoneal cavity and harbor a signature translocation-t(11;22)(p13,q12). In the paratestis they often involve the surface of the epididymis. The MNTI is an enigmatic, histologically distinctive, low-grade neoplasm occasionally encountered in the epididymis. Recognition of its features is essential to avoid misdiagnosis as a more aggressive "small blue cell" neoplasm and consequent therapeutic mismanagement. Primary hematopoietic tumors of the paratesticular structures are rare. There appears to be a tendency for young men to have low-grade lymphomas with an indolent course and older patients to develop higher-grade tumors. Plasmacytoma and granulocytic sarcoma of the paratestis are even more rare and are often susceptible to misinterpretation. Finally, metastatic tumors and a variety of other very rare neoplasms are discussed. PMID- 11202549 TI - Paratesticular tumor-like lesions. AB - The diverse non-neoplastic lesions that occur in the paratesticular region and may potentially mimic neoplasms are considered. These include some aspects of normal histology such as a cribriform pattern of the epididymis, bizarre nuclear atypia within epididymal epithelial cells and the presence of Leydig cells outside the testicular parenchyma. Inflammatory changes associated with a hydrocele and a variety of granulomatous and nongranulomatous infectious disorders may mimic a neoplasm on gross evaluation, but should be readily distinguished from them microscopically. This is also the case with malakoplakia and sarcoidosis, which rarely form a paratesticular mass. Other lesions considered are changes associated with vasculitis, the recently described entities inflammatory pseudotumor and fibromuscular hyperplasia and the well known processes sperm granuloma, spermatocele, vasitis nodosa, fibrous pseudotumor, meconium periorchitis, mesothelial hyperplasia, the testicular tumor of the adrenogenital syndrome, sclerosing lipogranuloma, and splenic-gonadal fusion. Features that aid in the microscopic distinction of these lesions from neoplasms are emphasized. PMID- 11202550 TI - Pet travel: MAFF issues proposals for reforming quarantine rules. PMID- 11202552 TI - Non-infectious factors associated with macroscopic and microscopic lung lesions in slaughter pigs from farrow-to-finish herds. AB - A cross-sectional epidemiological study was conducted in 150 randomly selected farrow-to-finish herds to investigate which non-infectious factors might act as risk indicators for the prevalence and severity of macroscopic and microscopic lung lesions in slaughter pigs. Data were collected during herd visits through inspections of the pigs and through interviews with the farmers. Macroscopic lung lesions of pneumonia and pleuritis were recorded at slaughter from 25 pigs per herd, and microscopic lung lesions of lymphohistiocytic infiltration were recorded from 10 pigs per herd. The median herd level prevalences were 24 per cent for pneumonia, 16 per cent for pleuritis and 60 per cent for lymphohistiocytic infiltration. Pneumonia lesions were negatively associated with pleuritis lesions and positively associated with lymphohistiocytic infiltration. Pleuritis lesions were negatively associated with lymphohistiocytic infiltration. The prevalence and the severity of pneumonia lesions were increased by a high frequency of purchasing gilts and by a slaughter date in January to February. The presence of a growing unit also increased the severity of pneumonia. The prevalence and the severity of pleuritis lesions were higher when there were more pig herds in the municipality, and when there were poor biosecurity measures, and their prevalence was increased by a slaughter date in January to February, and their severity by a slaughter date in March to April. An increase in the airspace stocking density in the finishing unit also increased the prevalence of pleuritis. The prevalence and the severity of lymphohistiocytic infiltration in the lung tissue were higher in herds purchasing gilts. Pigs raised in pens with slatted floors were also at higher risk of more severe lesions of lymphohistiocytic infiltration. PMID- 11202551 TI - Acute phase proteins in serum and milk from dairy cows with clinical mastitis. AB - The serum concentrations of haptoglobin, serum amyloid A and alpha1 acid glycoprotein were determined in serum collected from healthy dairy cows and cows with clinical mastitis, graded as mild (clots in milk) or moderate (clots in milk and visible signs of inflammation in the mammary gland/s) to assess their relative diagnostic value in detecting the disease. The concentrations of haptoglobin and serum amyloid A were also measured in milk collected from infected and uninfected quarters. The concentrations of haptoglobin and serum amyloid A were higher in the serum and milk from the cows with mild or moderate mastitis. The diagnostic value of haptoglobin in differentiating between healthy animals and those with mastitis gave sensitivities and specificities of 82 per cent and 94 per cent respectively with serum and 86 per cent and 100 per cent with milk. The diagnostic value of serum amyloid A in differentiating between healthy animals and those with mastitis gave sensitivities and specificities of 83 per cent and 90 per cent with serum and 93 per cent and 100 per cent with milk. The diagnostic value of serum alpha1 acid glycoprotein in differentiating between healthy animals and those with mastitis gave sensitivities and specificities of 62 per cent and 91 per cent. PMID- 11202553 TI - Echocardiography of the normal bovine heart: technique and ultrasonographic appearance. AB - Fifty-one clinically healthy cows were examined ultrasonographically from the third and fourth intercostal spaces on both sides of the thorax. A 3.0 MHz transducer was used and the heart was examined in the caudal long, caudal short and cranial long axes on the right side, and in the caudal and cranial long axes on the left side. In each position the optimal transducer orientation and the images of the structures were recorded. In the caudal long axis view of the heart on the right (transducer positioned at the fourth intercostal space), all four chambers were visible with the transducer positioned 8 to 10 cm dorsal to the level of the olecranon. The left ventricular outflow tract, consisting of the aortic valve and ascending aorta, were visible in the same position with the transducer rotated 10 to 40 degrees clockwise. In the caudal short axis view of the heart on the right, the left and right ventricles were visible in cross section with the transducer held at right angles to the ribs in the fourth intercostal space, 3 to 6 cm dorsal to the olecranon and tipped slightly dorsally. In the cranial long axis view of the heart on the right, the right ventricular outflow tract, consisting of the pulmonary valve and pulmonary artery, was visible in the third intercostal space, 8 to 10 cm dorsal to the olecranon with the transducer angled craniodorsally and rotated 10 to 20 degrees clockwise. In the caudal long axis view of the heart on the left, the left and right ventricles and the left ventricular outflow tract were visible with the transducer placed in the fourth intercostal space. In the cranial long axis view on the left, the right ventricular outflow tract was visible. PMID- 11202554 TI - First confirmed native case of bovine spongiform encephalopathy in Denmark. PMID- 11202555 TI - Lack of association between retention of fetal membranes and mastitis in ewes. PMID- 11202556 TI - Caryospora species in a snowy owl (Nyctea scandiaca). PMID- 11202557 TI - Cutaneous nodular phaeohyphomycosis in five horses associated with Alternaria alternata infection. PMID- 11202558 TI - Phillips report and the origin of BSE. PMID- 11202559 TI - Neutering of dogs. PMID- 11202560 TI - Alopecia X in dogs. PMID- 11202561 TI - Hibernated human fetal striatal tissue: successful transplantation in a rat model of Huntington's disease. AB - The use of fresh human fetal tissue in neural transplantation presents considerable logistical difficulties and limits the clinical applicability of this promising therapy. This study compared the survival of human fetal striatal tissue that had been stored for 24 h in a defined hibernation medium with that of fresh human fetal striatal tissue following xenotransplantation in a rat model of Huntington's disease (HD). Six to 7 weeks postgrafting, there was no significant difference between fresh and hibernated grafts in volume or in various striatal phenotypic markers, although there was a trend towards decreased graft volume. We conclude that short-term hibernation of this tissue is without significant adverse effects on the survival of grafted human fetal striatal tissue. This has important implications for the practical implementation of clinical neural transplant programs in HD. PMID- 11202562 TI - The effects of taurine on hNT neurons transplanted in adult rat striatum. AB - Taurine acts as an antioxidant able to protect neurons from free radical-mediated cellular damage. Moreover, it modulates the immune response of astrocytes that participate in neurodegenerative processes. The objective of this study was to examine whether taurine can prevent or attenuate the host inflammatory response induced by the xenotransplantation of neurons derived from the human teratocarcinoma cell line (hNT neurons). Male Sprague-Dawley rats were treated IP with either saline or taurine. Animals from both groups were perfused on the 4th or 11th day and the saline or taurine was administered from the start of the study until the day prior to sacrifice. The brains were processed immunohistochemically using antibodies against glial fibrillary acidic protein (GFAP), microglia (OX42), and human nuclear matrix antigen (NuMA). In the saline group, NuMA labeling revealed small grafts on the 4th day and no surviving cells on the 11th day. However, in the group that received taurine there were surviving grafts at both time points. Strong immunoreactivity for GFAP and OX42 was detected in the saline group surrounding the transplant. These effects were reduced in animals receiving taurine. Taken together, these results demonstrated that taurine was able to facilitate graft survival and attenuate the immune response generated by the xenograft. PMID- 11202563 TI - A new type of biocompatible bridging structure supports axon regrowth after implantation into the lesioned rat optic tract. AB - We have developed a new type of polymer/cell/matrix implant and tested whether it can promote the regrowth of retinal ganglion cell (RGC) and other axons across surgically induced tissue defects in the CNS. The constructs, which consisted of 2-2.5-mm-long polycarbonate tubes filled with lens capsule-derived extracellular matrix coated with cultured neonatal Schwann cells, were implanted into lesion cavities made in the left optic tract (OT) of 18-21-day-old rats. In one group, to promote Schwann cell proliferation and perhaps also to stimulate axon regrowth, basic fibroblast growth factor (bFGF) was added to the lens capsule matrix prior to implantation. In another group, to determine whether application of growth factors to the somata of cells enhances the regrowth of distally injured axons, the neurotrophin NT-4/5 was injected into the eye contralateral to the OT lesion. NT-4/5 and bFGF treatments were combined in some rats. After medium-term (4-10 weeks) or long-term (15-20 weeks) survivals, axon growth into implants was assessed immunohistochemically using a neurofilament (RT97) antibody. RGC axons were visualized after injection of WGA/HRP into the right eye. Viable Schwann cells were present in implants at all times after transplantation. Large numbers of RT97+ axons were consistently found within the bridging implants, often associated with the peripheral glia. Axons were traced up to 1.7 mm from the nearest CNS neuropil and there was immunohistochemical evidence of myelination by Schwann cells and by host oligodendrocytes. There were fewer RGC axons in the implants, fibers growing up to 1.6 mm from the thalamus. Neither NT-4/5 nor bFGF, alone or in combination, significantly increased the extent of RGC axon growth within the implants. A group of OT-lesioned rats was implanted with polymer tubes filled with 2-2.5-mm-long pieces of predegenerate peripheral nerve. Surprisingly, polymer/cell/matrix constructs contained comparatively greater numbers of RGC and other axons and supported more extensive axon elongation. Thus, implants of this type may potentially be useful in bridging large tissue defects in the CNS. PMID- 11202564 TI - Alginate-encapsulated producer cells: a potential new approach for the treatment of malignant brain tumors. AB - In recent years gene therapy has evolved as a new treatment for brain tumors, where genetically engineered cells can be used to deliver specific substances to target cells. However, clinical success has been limited due to insufficient gene transfer, lack of prolonged gene expression, and immunorejection of producer cells. These obstacles may be overcome by encapsulating producer cells into immunoisolating substances such as alginate. This may provide a stable in situ delivery system of specific proteins, which can interfere with tumor growth and differentiation. This article represents a fundamental study describing the in vitro and the in vivo behavior of alginate-encapsulated producer cells. The viability and cell cycle distribution of encapsulated NIH 3T3 cells was studied by confocal laser scanning microscopy (CLSM) and by flow cytometry. The CLSM study showed a high viability of the encapsulated NIH 3T3 cells during 9 weeks in culture. The flow cytometric analysis revealed a change in cellular ploidy after 1 week in culture, with normalization in ploidy after 3 and 9 weeks. The production of the bacterial E. coli beta-galactosidase in alginate-encapsulated BT4CnVlacZ cells was studied by x-gal staining, and the cells expressed prolonged beta-galactosidase activity. H528 hybridoma cells producing monoclonal antibodies (mAbs) against the human epidermal growth factor receptor (EGFR) were encapsulated in alginate, and the mAb release was determined. The release of mAbs stabilized around 400 ng/ml/h after 12 days in vitro. To actually demonstrate that alginate-encapsulated H528 cells potentially inhibit a heterogeneous glioma cell population, cell migration from human GaMg glioma spheroids was studied during stimulation with EGF in the presence of encapsulated H528 cells. The migration in vitro was totally inhibited in the presence of H528 encapsulated cells. Alginate beads with H528 cells were also implanted into rat brains, and after 9 weeks the distribution of mAbs within the brain was studied by immunohistochemistry. It is shown that the alginate entrapped H528 cells produce mAbs inside the brain for prolonged periods and that the mAbs are distributed within all CSF compartments. Encapsulated producer cells represent a potential delivery system for specific proteins to brain tumors. Different producer cells may be encapsulated in alginate to target phenotypic features and microenvironmental factors, which may influence the progressive growth of brain tumors. PMID- 11202565 TI - Agarose enhances the viability of intraperitoneally implanted microencapsulated L929 fibroblasts. AB - To achieve immunoisolation, mouse L929 fibroblasts were encapsulated in approximately 400 microm poly(hydroxyethyl methacrylate-co-methyl methacrylate) (HEMA-MMA) microcapsules and were subsequently implanted in the peritoneal cavity of syngeneic C3H mice. As a baseline for the use of genetically engineered cells in cell encapsulation therapy, the L929 cells were transfected to express a secreted form of human alkaline phosphatase (SEAP). Implantation of empty microcapsules in a PBS suspension resulted in deformation, aggregation, and poor retrievability of the microcapsules. Incubation of microcapsules with medium containing xenogeneic horse serum prior to implantation increased the thickness of the fibrous tissue surrounding the microcapsules. However, immobilization of the microcapsules in a 4% (w/v) SeaPlaque agarose gel prior to implantation allowed complete recovery of the microcapsules and prevented their aggregation and deformation. As a result, approximately 50% of the encapsulated cells remained viable 21 days postimplantation. Moreover, once the viable cells were released from retrieved microcapsules and regrown as monolayers, they expressed SEAP at a level similar to their encapsulated but nonimplanted counterparts. PMID- 11202566 TI - Acutely sodded expanded polytetrafluoroethylene grafts produce only prostacyclin: a qualitative difference from saphenous veins. AB - Select subsets of patients require prosthetic graft material for revascularization. Although arterial prosthetic grafts of large caliber perform acceptably, grafts of <6 mm exhibit a high attrition rate. Microvessel endothelial sodding, a method resulting in the lining of prosthetic grafts with autologous endothelium, improves graft patency; however, aggressive antiplatelet therapy is still required, because terminating an antiplatelet regimen accelerates graft attrition. The present investigation was designed to address the acute production of vasoactive substances in microvessel endothelial cell sodded expanded polytetrafluoroethylene (ePTFE) grafts in an attempt to delineate a possible mechanism behind the continued requirement for antiplatelet therapy. Equal lengths of acutely sodded ePTFE grafts (canine falciform ligament source) and saphenous veins (SV) (canine source) were evaluated by superfusion bioassay. Basal secretion from ePTFE grafts relaxed the biodetector ring 1 +/- 3%, whereas SV relaxed the ring 10 +/- 3% (p < 0.05, ePTFE vs. SV). Relaxation with acetylcholine stimulation was 49 +/- 7% in grafts and 50 +/- 10% in veins (p = NS). Calcium ionophore stimulation produced relaxation of 37 +/- 9% from ePTFE grafts and 100 +/- 23% from SV (p < 0.05). Indomethacin added to perfusate reduced relaxations from sodded ePTFE grafts to 20.2 +/- 9.2% with acetylcholine stimulation and 12.5 +/- 4.3% with calcium ionophore (p < 0.05 vs. control); addition of N(G)-monomethyl-L-arginine (L-NMMA) had no effect on the release of vasoactive substances from ePTFE grafts. In contrast, relaxations of effluent from SV stimulated by acetylcholine and calcium ionophore were significantly attenuated with indomethacin and L-NMMA (p < 0.05 vs. control). Scanning electron microscopy demonstrated confluent endothelium in SV and a nonconfluent endothelial cell layer in grafts. Acutely sodded ePTFE grafts produce vasoactive substances that quantitatively and qualitatively differ from those produced by canine SV. The ePTFE grafts produce mainly prostanoids, whereas SV produce both nitric oxide and prostanoids. The endothelial cell isolation procedure and absence of immediate graft luminal confluence may contribute to the observed differences. PMID- 11202567 TI - The Cre-loxP system: a versatile tool for targeting genes in a cell- and stage specific manner. AB - Gene-targeted mice, derived from embryonic stem cells, are useful tools to study gene function during development. However, if the inactivation of the target gene results in embryonic lethality, the postdevelopmental function of the gene cannot be further studied. The Cre recombinase-loxP (Cre-loxP) system was developed to overcome this limitation as well as to confine the inactivation of the target gene in a cell- or tissue-specific manner. This system allows for the inactivation of the target gene in a single cell type, thereby allowing the analysis of physiological and pathophysiological consequences of the genetic alteration in mature animals. A unique property of the insulin gene to be expressed only in pancreatic beta cells has allowed using the beta-cell-specific rat insulin promoter (RIP) for Cre recombinase expression to inactivate genes in beta cells. The RIP has been used to inactivate genes in beta cells and analysis of these genetically altered mice has provided important information regarding the role of potential transcription factors and the receptors in vivo, for regulation of insulin gene transcription and in the development of beta cells. The Cre-loxP system is at a relatively early stage of development, and the ability of this technique to virtually target any gene in any tissue at any stage of development makes the study of gene function in a single cell type in vivo an attainable goal. It is anticipated that the continued experience with this system will provide an important tool to determine the role of the transcription factors involved in insulin gene regulation and islet cell differentiation and ultimately provide the basis for novel therapy to treat diabetes. PMID- 11202568 TI - ICAM-1 antisense oligodeoxynucleotide improves islet allograft survival and function. AB - Expression of intercellular adhesion molecule-1 (ICAM-1) and its ligand, leukocyte function antigen-1 (LFA-1), after pancreatic islet transplantation may affect both nonspecific and alloantigen-specific phases of graft destruction. We examined the effects of ICAM-1/LFA-1 blockade on the survival of islet allografts. Fresh C57BL/10 (H2h) pancreatic islets were transplanted under the renal subcapsular space (KC) or embolized into the liver after portal vein (PV) injection to C3H (H2k) mice. Recipients remained untreated or were treated for 7 days by i.p. administration of: ICAM-1 antisense phosphorothioate oligodeoxynucleotide (oligo) alone; anti-1CAM-1 (alphaICAM-1) monoclonal antibody (mAb) alone: alphaLFA-1 mAb alone; ICAM-1 oligo/alphaLFA mAb combination; alphaICAM-1 mAb/alphaLFA-1 mAb combination; or control oligo IP-8997 or IP-1082. In some experiments, donors were pretreated with ICAM-1 oligo. Inhibition of single ligand with 5.0 mg/kg ICAM-1 oligo (25.1 +/- 10.3), 100 microg/daily alphaICAM-1 mAb (24.2 +/- 8.0 days), or 50 microg/daily alphaLFA-1 mAb (42.8 +/- 25.9 days) prolonged the survivals of KC islet allografts in comparison with untreated controls (11.9 +/- 1.0 days; all p < 0.01). However, dual ICAM-1/LFA-1 blockade with either ICAM-1 oligo/alphaLFA-1 mAb (78.3 +/- 16.5 days) or (alphaICAM-1 mAb/aLFA-1 mAb (65.2 +/- 31.3 days) was the most effective therapy. Although pretreatment of donors with ICAM-1 oligo alone was ineffective (12.2 +/- 0.8 days; NS), a combination of donor pretreatment and recipient treatment started 1 day prior to grafting with ICAM-1 oligo (39.2 +/- 14.0 days) was more effective than the recipient treatment alone (24.6 +/- 8.8 days). Furthermore, ICAM-1/LFA-1 blockade improved islet function as evaluated by glucose tolerance test, and decreased inflammation in comparison with untreated controls. Similar in vivo results were obtained following PV administration of islet allografts. Thus, ICAM-1/LFA-1 blockade prolongs the survival of pancreatic islet allografts and improves their early function. PMID- 11202569 TI - Development and characterization of pituitary GH3 cell clones stably transfected with a human proinsulin cDNA. AB - Successful beta-cell replacement therapy in insulin-dependent (type I) diabetes is hindered by the scarcity of human donor tissue and by the recurrence of autoimmune destruction of transplanted beta cells. Availability of non-beta cells, capable of releasing insulin and escaping autoimmune recognition, would therefore be important for diabetes cell therapy. We developed rat pituitary GH3 cells stably transfected with a furin-cleavable human proinsulin cDNA linked to the rat PRL promoter. Two clones (InsGH3/clone 1 and 7) were characterized in vitro with regard to basal and stimulated insulin release and proinsulin transgene expression. Mature insulin secretion was obtained in both clones, accounting for about 40% of total released (pro)insulin-like products. Immunocytochemistry of InsGH3 cells showed a cytoplasmic granular insulin staining that colocalized with secretogranin II (SGII) immunoreactivity. InsGH3 cells/clone 7 contained and released in vitro significantly more insulin than clone 1. Secretagogue-stimulated insulin secretion was observed in both InsGH3 clones either under static or dynamic conditions, indicating that insulin was targeted also to the regulated secretory pathway. Proinsulin mRNA levels were elevated in InsGH3 cells, being significantly higher than in betaTC3 cells. Moreover, proinsulin gene expression increased in response to various stimuli, thereby showing the regulation of the transfected gene at the transcriptional level. In conclusion, these data point to InsGH3 cells as a potential beta-cell surrogate even though additional engineering is required to instruct them to release insulin in response to physiologic stimulations. PMID- 11202570 TI - Insulin-secreting pituitary GH3 cells: a potential beta-cell surrogate for diabetes cell therapy. AB - In a companion article, we describe the engineering and characterization of pituitary GH3 cell clones stably transfected with a furin-cleavable human insulin cDNA (InsGH3 cells). This article describes the performance of InsGH3 (clones 1 and 7) cell grafts into streptozotocin (STZ)-induced diabetic nude mice. Subcutaneous implantation of 2 x 10(6) InsGH3 cells resulted in the progressive reversal of hyperglycemia and diabetic symptoms, even though the progressive growth of the transplanted cells (clone 7) eventually led to glycemic levels below the normal mouse range. Proinsulin transgene expression was maintained in harvested InsGH3 grafts that, conversely, lose the expression of the prolactin (PRL) gene. Elevated concentrations of circulating mature human insulin were detected in graft recipients, demonstrating that proinsulin processing by InsGH3 cells did occur in vivo. Histologic analysis showed that transplanted InsGH3 grew in forms of encapsulated tumors composed of cells with small cytoplasms weakly stained for the presence of insulin. Conversely, intense insulin immunoreactivity was detected in graft-draining venules. Compared to pancreatic betaTC3 cells, InsGH3 cells showed in vitro a higher rate of replication, an elevate resistance to apoptosis induced by serum deprivation and proinflammatory cytokines, and significantly higher antiapoptotic Bcl-2 protein levels. Moreover, InsGH3 cells were resistant to the streptozotocin toxicity that, in contrast, reduced betaTC3 cell viability to 50-60% of controls. In conclusion, proinsulin gene expression and mature insulin secretion persisted in transplanted InsGH3 cells that reversed hyperglycemia in vivo. InsGH3 cells might represent a potential beta-cell surrogate because they are more resistant than pancreatic beta cells to different apoptotic insults and might therefore be particularly suitable for encapsulation. PMID- 11202571 TI - Human pancreatic islets transfected to produce an inhibitor of TNF are protected against destruction by human leukocytes. AB - The objective of this study was to determine whether transfection of human islets with an adenovirus construct encoding an inhibitor of tumor necrosis factor (TNFi) was effective at limiting damage to beta cells induced by human peripheral blood leukocytes (huPBL). Human islets transfected with TNFi or control islets were transplanted under the kidney capsule of NOD-scid mice. After a 15-day engraftment period, half of the mice received injections of activated huPBL and half received buffer injections. Islet graft function was assessed by two different methods, both of which use a species-specific radioimmunoassay to determine human insulin. In some mice, insulin production following intraperitoneal glucose injection was determined in serum. In other mice, total graft insulin content was determined by acid ethanol extraction. Histochemical stains were performed on some kidneys at the termination of the experiment to evaluate graft presence, transgene expression, and huPBL infiltration. In huPBL injected mice, graft performance was maintained in mice whose grafts were transfected with TNFi but declined substantially in control groups with sham transfected or beta-galactosidase transfected islet grafts. Similar results were obtained using either glucose-stimulated insulin release or graft insulin content as a measure of graft survival. There was no significant difference in graft function between control groups receiving buffer injections, regardless of whether the islets had been transfected. Human leukocytes were found in all huPBL groups regardless of islet transfection status. We conclude that transfection of human islets with an adenovirus encoding TNFi protects beta cells from destruction induced by human leukocytes. The local production of TNFi does not prevent graft infiltration by leukocytes, only the destruction of grafts by the infiltrating leukocytes. These results raise the possibility that local expression of an inhibitor of the proinflammatory cytokine TNF-alpha may also prevent graft failure in clinical islet transplantation. PMID- 11202572 TI - A large-animal model to evaluate the clinical potential of fetal pig pancreas fragment transplantation. AB - The long-term goal of this study is to assess the feasibility of using fetal pig pancreas fragment (FPPF) transplantation to treat patients with type I diabetes. Using the highly inbred Westran Pigs, our initial aim was to establish a rejection-free transplant model of FPPF grafted into sibling recipient pigs without immunosuppression. FPPFs were isolated from 80-100-day-old fetuses of either Westran Pigs or outbred pigs and transplanted into the thymus, spleen, liver, or kidney of the recipient Westran pig. Biopsies were taken from each transplant site at set time points and assessed histologically for islet viability, rejection, and endocrine function. Fifty-eight fetal donors were used to transplant 16 recipient pigs. A nonspecific inflammation was seen for both outbred and inbred FPPF donor tissue at day 3 and was considered a response to ischemic necrosis. However, all the transplanted outbred FPPF donor tissue was acutely rejected and lost by day 10-14. In contrast, inbred FPPF tissue showed little evidence of graft necrosis after 3 days, and growth and formation of epithelial islet cell nest-like structures were seen to 28 days after transplantation. With time after transplantation, increasing amounts of insulin immunoperoxidase staining was seen together with chromogranin and somatostatin staining. In summary, this study confirms the potential of the Westran pig to answer the unproven ability of fetal pancreatic tissue to reverse type I diabetes in a large animal model. PMID- 11202573 TI - Induction of allogeneic islet tolerance in a large-animal model. AB - For islet allotransplantation to become a therapy widely applicable to patients with insulin-dependent diabetes, it will be important to avoid conventional immunosuppression and yet maintain long-term rejection-free islet survival. This possibility was tested in a large-animal model using mixed allogeneic chimeras established using total lymphoid irradiation (TLI) and donor-specific bone marrow transplantation (BMTX). Four recipient sex-mismatched and DLA class II-matched English springer spaniels became chimeric after TLI and donor-specific BMTX. Subsequent donor-specific renal allografts survived for more than a year. Acceptance of a donor-specific skin graft and rejection of a third-party graft demonstrated tolerance with maintenance of immunocompetence. Pancreatic microfragments containing islets were refluxed into the splenic vein of the recipient. Purified islets were placed under the capsule of spleen and liver. After 75 days, recipients underwent total native pancreatectomy. All four chimeric pancreatectomized dogs had functioning islet grafts 75 days after transplantation, evidenced by a prompt rise in serum insulin levels following an IVGTT and histological demonstration of islet tissue at the site of transplantation. After removal of the transplanted islet tissue, no insulin was released after IVGTT. In summary, intrasplenic allogeneic canine islets transplanted into chimeric dogs rendered tolerant to donor MHC survive and function for greater than 75 days in the absence of immunosuppression. This study represents proof of the concept that allogeneic islet transplants have the potential to reverse diabetes without the use of conventional immunosuppression. PMID- 11202574 TI - Simultaneous pancreas-kidney (SPK) transplantation from controlled non-heart beating donors (NHBDs). AB - From January 1993 through June 1999, 18 simultaneous pancreas-kidney transplants (SPKs) were performed from controlled non-heart-beating donors (NHBDs) and 339 SPKs were performed from heart-beating donors (HBDs). No difference in donor characteristics was noted except for warm ischemic time, which was 14.8 min (range 4-46 min) for NHBDs. Following transplantation, no difference in pancreatic function was noted; however, a higher rate of enteric conversions was seen in pancreas transplants from NHBDs (32% vs. 13%; p < 0.01). Hemodialysis for acute tubular necrosis (ATN) was higher in kidney transplants from NHBDs (22.2% vs. 4.1%; p = 0.009) as was discharge serum creatinine (1.7 mg/dl vs. 1.5 mg/dl; p < 0.05). Also, the number of patients remaining rejection free was lower for NHBDs and approached significance (33.3% vs. 50.1%; p = 0.07). However, no difference in patient survival (100% vs. 95.4%) or pancreatic (87.4% vs. 86.5%) and renal (86.3% vs. 86.3%) allograft survival was noted during the study period. Our results indicate that SPK transplantation from controlled NHBDs is a viable method for increasing the number of pancreas and kidney transplants available for transplantation. PMID- 11202575 TI - No evidence of infection with porcine endogenous retrovirus in recipients of encapsulated porcine islet xenografts. AB - Transplantation of pig tissues into humans has the potential for cotransferring pig infections. Knowledge of the epidemiology of pig infections transmissible to humans allows the development of risk limitation strategies at the source herd level, but potentially infectious pig endogenous retrovirus (PERV) is ubiquitous in all domestic pigs and therefore is not avoidable. Using a specific and sensitive RT-PCR and nested PCR for PERV nucleic acids with primers, the screening of pigs from New Zealand herds for the presence and expression of the PERV was conducted. The presence of PERV proviral DNA (pol and env region) and viral RNA was demonstrated in all tested pig tissues including pancreas, liver, spleen, brain, heart, and PBMC. Using the same assays it was established that different tissues (liver, spleen, and heart) of nude and nonobese diabetic (NOD) mice previously transplanted with nonencapsulated pig islets were PERV DNA and RNA negative. Alginate polylysine capsules prepared with encapsulated pig islets were tested for possible leakage of viral particles or viral nucleic acids. RNA was extracted from the supernatant of viable encapsulated pig islet cells grown in culture for 2 months. No evidence of PERV RNA or of cellular nucleic acids could be found. Two adult type I diabetic subjects were transplanted with 1 x 10(6) neonatal pig islets encased in alginate capsules into the peritoneal cavity. One patient was immunosuppressed. Both showed evidence of graft function (up to 34% reduction in insulin dose, corresponding increase in serum pig C peptide) for up to 2 years. DNA and RNA were extracted from PBMC and blood plasma of both patients at 19 months posttransplant. No evidence of PERV proviral DNA or RNA could be detected. Piglet islets contain PERV DNA and RNA, but this does not traverse the capsules used or produce any evidence of infection in nude and nonobese diabetic (NOD) mice or humans. PMID- 11202576 TI - Beneficial effect of pancreas and kidney transplantation on advanced diabetic retinopathy. AB - In pancreas recipients with advanced diabetic eye disease, conflicting ophthalmologic results over different follow-up periods have been reported. In the present prospective study we performed ophthalmologic evaluation groups of type I diabetic patients: 1) normoglycemic recipients of pancreas and kidney grafts (group SPK, n = 43, follow-up 44.9 +/- 35.1 months), 2) pancreas and kidney graft recipients with nonfunctioning pancreatic graft, and recipients of isolated kidney graft (group K, n = 45, follow-up 60.3 +/- 34.2 months). The examinations were performed before transplantation, at the end of follow-up (at least 1 year), and in 63 recipients also at 3 years posttransplant. Visual acuity results at baseline and at the end of follow-up were 0.48 +/- 0.39 vs. 0.50 +/- 0.39 in the SPK group, and 0.46 +/- 0.38 vs. 0.40 +/- 0.39 in the K group. While intragroup changes were not significant, the changes were significantly different between the groups (p < 0.05). Fundoscopic findings at the end of follow-up were improved, stabilized, or deteriorated in the SPK group in 21.3%, 61.7%, and 17.0%, respectively. The respective figures for the K group were 6.1%, 48.8%, and 45.1% (p < 0.001). Similar results were obtained when evaluating findings at 3 years posttransplant. Before transplantation, 78% of the SPK group and 81% of the K group had been treated by laser. The need for additional posttransplant laser therapy was significantly lower in the SPK (31%) than in the K group (58%; p < 0.001). In conclusion, pancreas transplant exerts a beneficial effect on the course of diabetic retinopathy even in its late stage. PMID- 11202578 TI - Sustained improvements in cardiac geometry and function following kidney-pancreas transplantation. AB - Kidney-pancreas (KP) transplantation has been shown to improve left ventricular (LV) geometry and function 6-24 months after the procedure, yet whether these improvements are sustained in long-term survivors has not been demonstrated. This study examined whether early improvements in LV geometry and function were sustained 3-5 years after KP transplantation. Left ventricular function and geometry were prospectively evaluated prior to, and at 1, 2, and 3-5 years posttransplant using two-dimensional, M-mode, echocardiography with Doppler interrogation in the parasternal and apical views. The sample included 21 KP and a comparison group of 12 diabetic kidney-alone (KA) recipients. Long-term (3-5 years) data were obtained for KP recipients only. Although KA recipients had a longer duration of dialysis and worse diastolic function pretransplant, the groups were similar on other baseline measures. KA recipients experienced minimal improvements while KP recipients had significant improvements in cardiac function and geometry, both in terms of mean values and the percentage of KP recipients who experienced normalization posttransplant (p < 0.05). KP recipient improvements were also sustained at 3-5 years posttransplant on three of five measures, with 75% of long-term KP recipients achieving normal LV mass posttransplant compared with 31% pretransplant. Data indicate that significant impairments in cardiac geometry and function occur in diabetic KA and KP recipients. Though both groups experienced early improvements posttransplant, KP recipients achieved more dramatic and clinically significant improvements at 1, 2, and 3-5 years posttransplant. Additional studies are needed to examine the relevance of these findings with regard to the cardiac morbidity and mortality of these patients. PMID- 11202577 TI - Successful suppression of the early rejection of pig islets in monkeys. AB - Primary nonfunction (PNF) is seen very frequently after xenogeneic transplantation of islets of Langerhans. In a pig-to-rat model we recently observed that no PNF occurs when the islets are kept in culture at 37 degrees C for 1-2 weeks prior to transplantation. In order to investigate the rejection mechanisms in a preclinical model, we transplanted cultured porcine islets under the capsule of both kidneys in four cynomolgous monkeys. Islets were isolated from adult sows by means of digestion with Liberase in University of Wisconsin solution (UWS). The digest was purified by a density gradient of OptiPrep in UWS. Highly purified (>95%) islets were cultured 1-2 weeks in RPMI. All monkeys showed significant titers of preformed anti-pig antibodies. The immunosuppression of the monkeys consisted of cyclophosphamide (Cy) (2 days), cyclosporin A (CsA), and prednisolone. Anticipating a fast rejection we carried out nephrectomies at different time points within 2 weeks after transplantation. Following unilateral nephrectomy, well-preserved islets with no signs of rejection were observed between 3 and 7 days posttransplant. Later, between days 11 and 15 posttransplant, histology in the first three animals demonstrated no islets. In the fourth monkey histology on day 11 showed islets with excellent morphology and some small focal infiltrates. The highest CsA blood levels (around 1000 ng/ml) were found in animals with the best graft survival. We conclude that cultured porcine islets can be grafted without hyperacute rejection in monkeys with preformed anti-pig antibodies. In the presence of high levels of CsA only marginal signs of a cellular immune response were observed 11 days after transplantation. PMID- 11202579 TI - Improved solitary pancreas transplant graft survival in the modern immunosuppressive era. AB - The results of solitary pancreas (SP) transplantation have traditionally lagged behind those of simultaneous pancreas-kidney (SPK) transplantation. This is one of the chief factors that has limited the wide-scale application of SP transplantation in nonuremic type I diabetic patients. The purpose of this study is to report our present experience with SP transplantation and compare it to a prior experience. Twenty-three SP transplants (14 PAK, 4 PTA, and 5 PASPK) performed since January 1997 were compared to 56 SP transplants (53 PAK, 1 PTA, and 2 PASPK) performed before 1994. Between 1993 and 1997, SP transplants were not performed because of high morbidity in the early experience. Early SP transplants were performed using bladder drainage of exocrine secretions, and enteric drainage without a Roux-en-Y was used in the recent series. In the early era, immunosuppressive therapy included cyclosporine (CsA), azathioprine (AZA), corticosteroids, and in half of the patients, ALG or OKT3. Recent SP transplants received tacrolimus (TAC). mycophenolate mofetil (MMF), corticosteroids, and induction with either anti-thymocyte globulin (n = 9), OKT3 (n = 1), daclizumab (n = 5), or basiliximab (n = 8). The 1-year Kaplan-Meier patient survival was 85% in the early era and 100% in the recent group of patients (p = 0.08). In the previous era, four patients suffered significant decrement in renal function, necessitating dialysis or kidney transplantation following pancreas transplantation. All patients transplanted since 1997 maintain near prepancreas transplant levels of renal function (mean pretransplant serum creatinine (Cr) 1.3 +/- 0.3 mg/dl vs, mean current Cr 1.4 +/- 0.4 mg/dl, p = NS]. The 1-year Kaplan Meier graft survival (insulin independence) of recent SP transplants was 87%, whereas for prior SP transplants it was 19% (p = 0.0001). The rate of acute pancreas rejection was significantly different between the two groups. Of early SP transplants, 76% experienced at least one rejection episode within the first year. In contrast, 35% of recent SP transplants suffered acute rejection during the same time period (p = 0.04). Current experience with SP transplantation demonstrates improved graft survival and reduced rejection rates with the use of newer immunosuppressive agents. PMID- 11202581 TI - Evaluation of the prenatal diagnosis of neural tube defects by fetal ultrasonographic examination in different centres across Europe. AB - OBJECTIVE: Evaluation of prenatal diagnosis of neural tube defects by ultrasound examination in unselected populations across Europe. SETTING: Prenatal ultrasound units in areas that report to contributing congenital malformation registers. METHODS: All cases with a suspected or confirmed neural tube defect and delivered within the 30 month study period were identified from 18 Congenital Malformation Registers from 11 European countries. Data on the pregnancy, prenatal scans, outcome of pregnancy, and information on different screening policies for each country were analysed. RESULTS: 670766 deliveries occurred in the area covered by the registers during the study period. A neural tube defect was diagnosed at delivery in 542 cases. In 84% of these, the lesion was isolated (166 anencephaly, 252 spina bifida, 35 encephalocele). Of the 166 isolated cases with anencephaly, 96% were correctly identified prenatally; one was missed on scan, two were wrongly diagnosed, and four were not scanned (sensitivity 98%). 84% of the prenatal diagnoses were made before 24 weeks' gestation; 86% of isolated anencephalic pregnancies were terminated. Of the 252 cases of isolated spina bifida, 171 (68%) were correctly identified prenatally; 66% of these before 24 weeks' gestation. The diagnosis was missed on scan in 60 cases and 21 were not scanned (sensitivity 75%). The mean reduction in birth prevalence because of termination of pregnancy for spina bifida was 49% (range 6-100%). There was a wide variation between centres in prenatal detection rate (33-100%), termination of pregnancy of prenatally diagnosed cases (17-100%), and gestation both at diagnosis and termination of pregnancy. CONCLUSION: A high prenatal detection rate for anencephaly was reported by all registers. There is a large variation in prenatal detection and termination rates for spina bifida between centres, reflecting differences both in policy and culture. PMID- 11202580 TI - Patient survival and cardiovascular events after kidney-pancreas transplantation: comparison with kidney transplantation alone in uremic IDDM patients. AB - In diabetic patients cardiovascular morbidity and mortality is still a major problem. Our aim was to study the effect of kidney-pancreas transplantation on survival, cardiovascular events, and causes of death in diabetic type 1 uremic patients. Three hundred and thirty-three uremic IDDM patients were enrolled in our waiting list for kidney-pancreas transplantation: 107 underwent kidney pancreas transplantation (KP), 34 underwent kidney transplantation alone (KA), whereas 192 patients remained on dialysis (WL). Actuarial survival and causes of death were recorded over a period of 7 years. Seven-year survival rate was 75% for the KP group, 63% for the KA group, and 37% for the WL group (p = 0.001). Cardiovascular death rate was 9.8% in the KP group, 17.6% in the KA group, and 18.1% in the WL group (KP vs. WL, p = 0.05). Rate of acute myocardial infarction in the KP group was lower than in the KA group (2.4% vs. 17.6%, p = 0.005) as well as rate of acute pulmonary edema (0.8% vs. 23.5%, p = 0.0001) and rate of hypertensive patients at 1 (40.9% vs. 85.0%, p = 0.0001) and at 2 years (57.6% vs. 80%, p = 0.03). Kidney-pancreas transplant helped to obtain euglycemia with positive effects on survival and cardiovascular events. PMID- 11202582 TI - Opportunistic screening for chlamydia infection in general practice: can we reach young women? AB - OBJECTIVE: To study opportunistic screening in primary care, in such a way that would include teenage women. Setting-Screening for chlamydia infection was offered opportunistically in eight general practices in Edinburgh to women aged < or = 35 years attending for cervical smear, and women aged < or = 20 years attending for contraception. The numbers of women eligible to be offered screening were 901 in the cervical smear group, and 595 in the contraception group. RESULTS: Effective screening rate (offered test, consented, and urine sample returned) was 30% for the cervical smear group compared with 23% for the contraception group. Among those tested, chlamydia prevalence was strongly associated with young age, ranging from 11.8% in those <18 years, to 0% in those >25 years. Number of sexual partners in past year did not improve prediction of infection. CONCLUSION: These findings raise concerns regarding the feasibility of opportunistic screening in general practice, particularly for those with highest prevalence of chlamydia--teenage women. PMID- 11202583 TI - Radiological review of incidence breast cancers. AB - OBJECTIVES: To examine the rate of incidence cancers detectable on review of previous screening mammograms using two reviewing methods. To compare the results with a previous study of interval cancers using the same reviewing methods. SETTING: Almost 50000 women are regularly invited for service screening at Stockholm Soder Hospital. From 1989 to 1993, 119 women were identified with breast cancer detected at screening and the previous round attendance (incidence cancer). METHODS: Screening mammograms, obtained before detection of the incidence cancers, were reviewed first mixed with other screening images (ratio 1:8) and then non-mixed. Reviewers from the screening unit responsible for the mammograms as well as reviewers from other units interpreted all images by both single and double reading. RESULTS: The proportion detected on retrospective review varied between 5% and 50% depending on the review method used and the number of reviewers included to classify a case as truly identified. Generally more cancers were detected when non-mixed samples of mammograms were reviewed than when mixed samples were reviewed (mean increase 23%) and when interpreted by double reading compared with single reading (mean increase 14%). CONCLUSIONS: In an experimental retrospective set up, fewer incidence cancers were identified in mixed than in non-mixed review. Generally more incidence cancers were identified on review (22%) than previously reported for interval cancers (14%), probably reflecting differences in tumour biology and growth. How many women with potentially visible incidence cancers would have benefited from earlier tumour detection still needs to be evaluated. PMID- 11202584 TI - Radiological review of interval cancers in an Australian mammographic screening programme. Radiology Quality Assurance Group of BreastScreen Victoria. AB - OBJECTIVES: To determine the proportion and features of invasive interval cancers that could be considered detectable at the time of the previous screen and the proportion of cases that could be classified as true intervals, false negatives, minimal signs, or radiographically occult lesions. SETTING: BreastScreen Victoria, the Victorian component of the BreastScreen Australia mammography screening programme. METHODS: Two separate review methodologies were adopted. Firstly a blinded review of interval, screen detected, and normal cases was undertaken, followed by a confirmation exercise to determine the proportion of invasive interval cancers that could be considered detectable at the time of the previous screen. Secondly, an unblinded review was performed to classify interval cases as true interval, false negative, minimal signs, or radiographically occult. RESULTS: From the blinded review, it was estimated that 38% of interval cases may be considered "potentially detectable" at the time of screening. Comparison of the characteristics of interval and screen detected cases indicates that interval cases are more likely to be smaller, equivocal, ill defined masses. In the unblinded exercise, 41% of interval cases were classified as false negatives and a further 16% as minimal signs, 33% true intervals, and 10% radiographically occult. Of the interval cancers considered potentially detectable at screening, 97% were classified as false negatives in the unblinded review. CONCLUSIONS: This study highlights the importance of adopting staged review methods with both blinded and unblinded components. The blinded review and confirmation exercise allows the determination of the proportion of interval cases that could be considered potentially detectable at screening. The unblinded review provides an active important opportunity for professional development and review and a mechanism to link into the blinded review through further classification of interval cases. PMID- 11202585 TI - Predictors of non-attendance for second round mammography in an Australian mammographic screening programme. AB - OBJECTIVE: To determine the socioeconomic, cultural, and clinical predictors of non-attendance for second round mammography. DESIGN/PARTICIPANTS: Retrospective cohort study of 121 889 women aged 50-69 years who attended for first mammography screening in the BreastScreen Victoria programme in 1995/1996 and who were recommended to be invited for routine biennial mammography. Women were considered to be non-attenders if they had not attended for rescreening within 27 months of their initial screening. Relative risk (RR) was used to compare categories for non-attendance for second screening, and a multivariate model was fitted to adjust for possible confounding. SETTING: BreastScreen Victoria, a population based mammographic screening programme, which offers free biennial mammography to all women 40 years and older. The programme specifically targets women aged 50-69 years. RESULTS: In the multivariate analysis, women from non-English speaking backgrounds were more likely not to attend for second round screening (RR ranged from 1.18 to 1.77). Indigenous women (RR 2.02, 95% confidence interval (CI) 1.61 to 2.54) and women who reported either significant symptoms (RR 1.90, 95% CI 1.76 to 2.05) or other breast symptoms (RR 2.25, 95% CI 2.15 to 2.36) at the time of first round screening were also more likely not to attend for second round screening. CONCLUSIONS: Women from non-English speaking backgrounds, indigenous women, and women who report symptoms at the time of first screening are more likely to not attend for second round screening. It is important to investigate why these women do not attend for second round screening so that services can be more appropriately tailored to their needs. PMID- 11202586 TI - Results from the UK NHS breast screening programme 1994-1999. AB - OBJECTIVE: To present results from the NHS breast screening programme (NHSBSP) from 1994 through to 1999 and to examine the extent to which interim targets are being achieved. METHODS: Data were collated from all screening programmes in the UK on standard statistical returns. Performance of the screening programme was evaluated using calculated targets based on comparison with the Swedish two counties (STC) randomised controlled trial. RESULTS: In the early years of screening (1988-1993), the NHS programme was detecting more DCIS but considerably less invasive cancers than expected, based on the STC trial. Since the screening year 1993/94 (1 April to 31 March) the standardised detection ratio (SDR) measure of the detection of invasive cancers has increased by 36% from 0.83 to 1.13. The SDR has been greater than 1 since 1996197 suggesting that the NHSBSP has only been screening as efficiently as the STC trial since this date. Uptake for screening has been relatively stable over time at approximately 75%. CONCLUSIONS: The NHSBSP has made considerable advances in performance since its inception in 1988 and screening uptake and age standardised invasive cancer detection rates are (by 1999) well in excess of targets. The early years of screening were characterised by good uptake but a low sensitivity for the detection of invasive cancers. It is anticipated that the screening programme will have an increasing impact on breast cancer mortality, particularly in the 55-69 year age group over the coming years. PMID- 11202587 TI - Is targeted early detection for melanoma feasible? Self assessments of risk and attitudes to screening. AB - OBJECTIVES: To study the feasibility of developing targeted screening for those at high risk of melanoma by examining how attitudes relate to (a) acceptance of an invitation for a free skin check and (b) self assessed and clinically assessed risk factors for developing cutaneous melanoma. DESIGN: A population based cross sectional survey. SETTING: A general practice with a broad mix of socioeconomic groups in one district health authority. SUBJECTS: A total of 1600 subjects aged 25-69 years stratified using the social deprivation score of wards were randomly selected from a population of 8000; 77% (1227) returned the questionnaire and 56% (896) attended for screening. MAIN OUTCOME MEASURES: Questionnaire measures of confidence in own ability to self assess risk factors for melanoma, attitudes to seeking medical help for skin abnormalities, and self assessment of relative risk of developing melanoma. RESULTS: Clinic attenders were less confident in their ability to self assess risk factors (p<0.005), more favourable towards seeking help (p<0.001), and more pessimistic about developing melanoma (p<0.001) than non attenders. Those from more affluent wards were more willing to seek help (p<0.001). Those clinically assessed as at higher risk were more pessimistic about developing melanoma (p<0.001) but clinical assessments were inconsistently related to help seeking attitudes and self assessment confidence. CONCLUSIONS: Barriers to the uptake of screening included greater optimism about not developing melanoma, confidence in self assessment, and reluctance to seek professional help. Such reluctance was greater in more deprived social groups. Targeting screening at high risk groups cannot depend on self identification and self referral. PMID- 11202588 TI - Oral cancer screening as an integral part of general health screening in Tokoname City, Japan. AB - OBJECTIVES: To measure the attendance and compliance rates in oral mucosal screening (OMS) offered as part of a general health screen (GHS) undertaken as an organised programme in Japan. METHODS: In 1996, all adults over the age of 40 years resident in Tokoname City were invited by letter to attend a free GHS annually, conducted by the municipal cooperation and the medical and dental societies of Tokoname City. In the later years only those who attended in 1996 were reinvited. Females aged less than 39 years were also allowed to attend if they wished to participate in the GHS. The GHS consisted of completion of a self administered questionnaire to identify past and current illnesses and any medications used by the screened population coupled with a routine physical check, chest x ray, ECG, and blood and urine examination. The GHS was programmed annually during the years 1996 to 1998. All those attending the GHS were invited to participate in an OMS conducted under the same roof by a visiting dentist (n=37). A referral pathway was established for screen positives requiring follow up. RESULTS: A total of 19 305 subjects (5955 males, 13350 females; mean age 59.2 years; 7033 in 1996, 6289 in 1997, and 5983 in 1998) attended the GHS. Of those who attended the GHS, 19 056 (98.7%) attended the OMS (1.3% refused). This rate was fairly constant over the three years. Excluding repeat examinations, new cases recruited for OMS over the three years were 8723. Of those participating in OMS, 4269 (60.7%) attended all three years. In the cohorts examined, screening dentists recorded oral mucosal lesions in 5.4% in 1996, in 4.0% in 1997, and in 2.6% in 1998. Overall, this amounted to a positive detection rate of 4.1%, or 4.9% excluding repeat examinations. A higher prevalence of oral pre-cancer was recorded among male smokers. CONCLUSIONS: The overall results suggest that although compliance with attending a free GHS was low (26.2%) among Japanese subjects over 40 years of age, of those who complied 74-76% reattended annually. Hence a satisfactory participation rate can be obtained in Japan for OMS when this is coupled to a GHS conducted at the same visit. PMID- 11202590 TI - Revised distribution parameters for serum markers for trisomy 18. PMID- 11202589 TI - The potential for a selective screening strategy for abdominal aortic aneurysm. AB - OBJECTIVES: To investigate the feasibility of selective screening for abdominal aortic aneurysm (AAA) based on identification of a target group of manageable size defined by risk factors for AAA. SETTING: Male residents of Perth, Western Australia, aged 65-83 years, who participated in a randomised controlled trial of ultrasound screening for AAA. METHODS: Eligible men were identified from the electoral roll and invited to attend a screening clinic. Those who attended completed a questionnaire, had a limited physical examination, and underwent an ultrasound examination to identify the maximum diameter of the infrarenal aorta. Data on risk factors collected from the first 8995 men seen were used to calculate a multivariate risk score for the remaining 2755 men who were screened. Centiles of the risk score were used to define potential target groups for screening and the sensitivity and specificity of each of these selective screening strategies were calculated. We repeated the calculation separately for AAAs of at least 30 mm, 40 mm, and 50 mm in diameter. RESULTS: We found that screening half of the male population aged 65-83 years would find approximately 75% of AAAs, regardless of their size, whereas screening only current smokers in this population would find approximately 20% of AAAs. CONCLUSIONS: Selective screening for AAA using easily recognisable risk factors is feasible but is not worthwhile as approximately 25% ofclinically significant cases would be missed. PMID- 11202591 TI - Effective quality management groups. PMID- 11202592 TI - Psychological impact on house staff of an initial versus subsequent emergency medicine rotation. AB - The objective of this study was to assess the psychological impact of a 4-week emergency medicine (EM) rotation on residents undergoing their first EM experience. These findings were compared to the psychological impact the rotation had on residents with prior EM experience. Data were obtained from a post hoc analysis of a previous study. Prerotation and postrotation psychological distress levels were assessed over a 4-week EM rotation. Anxiety and depressive symptoms were evaluated by the Brief Symptom Inventory and the Dissociative Experience Scale that together comprise a total of 14 psychometric scales. All scales were given at the beginning and end of the initial EM rotation for the academic year of 1994-1995. All information was coded and confidential. Eighteen junior residents (9/18 EM [50%]) were analyzed as a group and compared to 53 residents (34/51 EM [66%]) with prior exposure to the authors' emergency department. Residents doing their first EM rotation (N = 18) showed improvement in 13 of 14 scales (P = .002). Of the 13 scales that improved, 3 improved significantly: Brief Symptom Inventory = anxiety (P = .002) and Dissociative Experience Scale = absorption (P = .001) and other (P = .001). Residents with prior EM experience (N = 53) displayed worsening in 9 of 13 scales (P = not significant) and no change in 1. Residents undergoing their first EM rotation showed a significant decrease in psychological distress over the 4-week period. Residents with prior EM experience did not show a similar change. PMID- 11202593 TI - Commentary: public disclosure in the health field: is there a relevant option? AB - Steadily increasing numbers of private, not-for-profit, and public agencies are releasing quality of care and financial information to enhance the market power of those purchasing America's health services. These sources range widely from the Health Plan Employer Data and Information Set (HEDIS) to the federal Securities and Exchange Commission (SEC). A growing interest in publicly disclosing performance information that concerns providers, as recently recommended by the Institute of Medicine (IOM) report on patient safety, until now has only achieved a modest impact. A major exception is in those metropolitan areas where acute-care facilities experience intense competition for patient admissions. Although the comparative quality and cost information currently available is for the most part in the public interest, it is concluded that, in the foreseeable future, these report cards as now structured will not result in any significant enhancement in access, improvement in quality, or reduction in cost. Options to encourage more public disclosure explored in this paper are Congress potentially passing legislation (a) to establish a Center for Patient Safety within the US Department of Health and Human Services as recommended by the recent Institute of IOM study, or (b) empowering the SEC beyond its current mandate to collect and disseminate all pertinent quality of care and cost information on every provider in the United States. The latter alternative would include user-friendly, comparative analyses to be provided on the Internet and elsewhere and would make readily available information from HEDIS, the Joint Commission on the Accreditation of Healthcare Organization (JCAHO), coronary artery bypass graft (CABG) surgery studies, cost comparisons based on Medicare cost reports and SEC filings, and other similar sources. PMID- 11202594 TI - Comparing self-reported measures of diabetes care with similar measures from a chart audit in a well-defined population. AB - The objective of this study was to compare self-reported measures of diabetes care with measures derived from medical records in a well-defined population. Diabetes measures were collected through a 1997 Behavioral Risk Factor Surveillance System telephone survey of American Indians living on or near 7 Montana reservations (N = 398) and were compared with data collected from charts of a systematic sample of American Indians with diabetes seen in 1997 at Indian Health Service (IHS) facilities. Survey respondents were more likely to report a duration of diabetes > or = 10 years (44 vs 31%), annual dilated retinal exam (75 vs 59%), and an influenza immunization in the past year (73 vs 57%) compared with estimates from the chart audit. Estimates of pneumococcal immunization (88 vs 42%), annual cholesterol screening (86 vs 69%), and overweight, based on body mass index (67 vs 50%), were significantly higher from the chart audit. No significant differences were found between the survey respondents and the chart audit data for annual foot exams (65 vs 61%), annual blood pressure checks (98 vs 93%), high cholesterol (35 vs 41%), and high blood pressure (54 vs 64%). These findings suggest that self-reported data may over and underestimate specific measures of diabetes care. PMID- 11202595 TI - Evaluating the implications of clinical practice guidelines for patient care. AB - Patient care evaluation studies have been developed by the Commission on Cancer of the American College of Surgeons. The studies were primarily designed to monitor trends in diagnosis, therapy, and outcome of specific oncologic diseases in hospitals and cancer centers. As they reflect the current standards of patient care, patient care evaluation studies have become valid tools of quality management in medicine. In an international pilot project that began in 1996, this approach was redefined to evaluate the impact of current clinical practice guidelines in oncology. Close cooperation between medical societies in the United States and Germany under the coordination of the Commission on Cancer and the Institute of Medical Informatics at the Justus-Liebig-University of Giessen was established. This infrastructure for data collection, data management, analysis, and interpretation of results allows for the recognition of international differences in patient care. Our results indicate discrepancies between current state-of-the-art patient care represented by clinical practice guidelines and the diagnostic and therapeutic procedures in the clinical routine. Patient care evaluation studies are designed as exploratory, not confirmatory, trials. In contrast with confirmatory trials, their aims may not always lead to predefined hypotheses. They reflect routine practice and are not the basis of the formal proof of efficacy, although they may contribute to the total body of relevant evidence. Without this comprehensive approach to evaluation, the potential of clinical practice guidelines to improve patient care remains unknown. PMID- 11202596 TI - Visual vignette: Grave's disease. PMID- 11202597 TI - Implementation of evidence and guidelines in clinical practice: a new field of research? PMID- 11202598 TI - The learning health care organization. PMID- 11202599 TI - Towards evidence-based quality improvement: perspectives from nursing practice. AB - This paper explores how the evidence-based practice and quality improvement movements are informing our understanding of what counts as quality patient care. Implicit in the debate is that we have understood and can manage the concept of patient safety. Using a true case study, the paper will illustrate how a clearer, more integrated understanding of safety, evidence-based practice and quality improvement principles can lead to more effective care. Central to this shift is the ability to move out of traditional, professionally bound ways of thinking to new systems and new ways of providing patient-centred care. Equally, how we generate the evidence to find out how safe or otherwise health care delivery systems are, must be as important an area of investigation as the search for a new therapy or treatment for a particular disease. PMID- 11202600 TI - National guidelines for Swedish neonatal nursing care: evaluation of clinical application. AB - OBJECTIVE: To evaluate the clinical application of national guidelines for neonatal nursing. DESIGN: Questionnaire survey. SETTING: Thirty-nine neonatal care units in Sweden. STUDY PARTICIPANTS: Thirty-five of 39 nurse managers at all Swedish neonatal care units. INTERVENTION: Thirteen clinical guidelines for neonatal nursing care were presented in 1997. Recommendations on evidence-based nursing care and auditing measures were given. Most neonatal units in Sweden participated in the guideline development. MAIN OUTCOME MEASURES: Extent of guideline application, ways in which the guidelines were used and perceived usefulness. RESULTS: The guidelines were applied to different extents in 30 of the 35 units. Almost all the guidelines were applied, especially those covering general nursing care. In total, 72 Quality Improvement (QI) projects were reported, of which 51 concerned specific topics covered in the guidelines. Twenty units applied the guidelines as a starting point for QI. Four units evaluated nursing practice against the guidelines. Four factors [Dynamic Standard Setting System (DySSSy) as the QI method, > or = 4 years of practice as nurse manager, experience of nursing research, and good staff resources] were closely related to a more extensive application of the guidelines. Units with both a nurse manager and an assistant nurse manager were more likely to have used the guidelines as the basis for changing clinical practice. CONCLUSIONS: The guidelines were successfully disseminated and diffused, but practitioner involvement in guideline development did not guarantee implementation. Downsizing, leadership and facilitation seemed to be crucial factors when getting evidence into practice. Limited occurrence of evaluations of clinical practice against guideline recommendations suggests a need for valid and user-friendly measures. PMID- 11202601 TI - Performance measurement for schizophrenia: adherence to guidelines for antipsychotic dose. AB - OBJECTIVE: This report describes the development, application, and exploratory evaluation of a clinical performance measure based on recently published schizophrenia guidelines for antipsychotic dose. DESIGN, SETTING, PARTICIPANTS: The performance measure, which assesses adherence to antipsychotic dose recommendations for acute schizophrenia treatment, was calculated at hospital discharge for 116 patients with schizophrenia who had participated in a 6-month outcomes study. MAIN OUTCOME MEASURE: The Brief Psychiatric Rating Scale (BPRS) was used to assess symptom severity at 6-month followup. RESULTS: At discharge, almost one-half of the patients were prescribed doses outside the recommended range. For the entire sample, linear regression models showed that the performance measure variable was not significantly associated with followup symptom severity (BPRS total scores). However, a significant association was observed for patients prescribed oral antipsychotics only (n = 69). Patients prescribed recommended doses had lower adjusted mean BPRS totals than patients prescribed doses either greater than (P < 0.05) or less than (P < 0.05) recommended. CONCLUSIONS: Our findings suggest that the antipsychotic dose performance measure may be useful for monitoring quality. It assesses a modifiable aspect of care for which clinical improvement is needed, and such improvement is likely to improve patient outcomes. Future research is needed to confirm our findings and to develop and test interventions to improve the quality of care for schizophrenia that incorporate this clinical performance measure. PMID- 11202602 TI - Assessing the necessity of hospital stay by means of the appropriateness evaluation protocol: how strong is the evidence to proceed? AB - OBJECTIVE: To review the Appropriateness Evaluation Protocol (AEP) with respect to assessing the necessity of hospital stay at the University Hospital of Maastricht. DESIGN: Literature search in Medline focusing on the validity, reliability and possibilities for intervention plus a description and the first results of pilot studies with a Dutch version of the Adult-Medical AEP (days of stay). SETTING: The University Hospital of Maastricht, a 700-bed university and regional hospital in the south of The Netherlands. MAIN OUTCOME MEASURES: Face, content, and convergent validity, and reliability in terms of overall or specific agreement and by kappa, of the Adult-Medical AEP when used by physicians and nurses. RESULTS: In comparison with other instruments, a comparatively good performance by the AEP has been reported in the literature. Literature review revealed limitations in the AEP as a general and truly valid and reliable instrument for assessing the necessity of hospital stay. In applying a Dutch version (azM-AEP) similar difficulties were encountered. CONCLUSION: Based on the literature review and our own findings, we conclude that the validity and reliability of the different versions of the AEP are not yet up to standard. Regarding the results of the interventions thus far, we do not encourage further use until additional improvements to both the instrument and the review conditions have been made. Perhaps a more disease-specific modulation and assessments based on computerized medical records could improve its applicability in clinical practice in general. PMID- 11202603 TI - An evaluation of the impact of training Honduran health care providers in interpersonal communication. AB - OBJECTIVE: To evaluate the impact of interpersonal communication (IPC) training on practice and patient satisfaction and to determine the acceptability of this training to providers in a developing country. DESIGN: The study used a pre-post design with treatment and control groups. Data collection methods included interaction analysis of audio-taped clinical encounters, patient exit interviews, and a self-administered questionnaire for health providers. STUDY PARTICIPANTS: Interaction analysis was based on an experimental group of 24 doctors and a control group of eight with multiple observations for each provider). Exit interviews were carried out with 220 pre-test patients and 218 post-test patients. All 87 health providers who received training responded to the self administered questionnaire. INTERVENTION: A brief in-service training programme on interpersonal communications was presented in three half-day sessions; these focused on overall socio-emotional communication, problem solving skills and counselling. MAIN OUTCOME MEASURES AND RESULTS: The IPC intervention was associated with more communication by trained providers (mean scores of 136.6 versus 94.4; P = 0.001), more positive talk (15.93 versus 7.99; P = 0.001), less negative talk (0.11 versus 0.59; P = 0.018), more emotional talk (15.7 versus 5.5; P = 0.021), and more medical counselling (17.3 versus 11.3; P = 0.026). Patients responded by communicating more (mean scores of 113.8 versus 79.6; P = 0.011) and disclosing more medical information (54.7 versus 41.7; P = 0.002). Patient satisfaction ratings were higher for providers who had received the training and providers reported training to be relevant and useful. CONCLUSIONS: Further validation of IPC skills and simplification of assessment methods are needed if IPC is to be an area for routine monitoring and quality improvement. PMID- 11202604 TI - Primary health care system in transition: the patient's experience. AB - OBJECTIVE: To find out how Estonian people evaluate the changes in primary health care (PHC), how they perceive the acceptability of the new PHC system, and to assess patients' satisfaction with their primary care doctor. DESIGN: Face-to face interviews using structured questionnaires. SETTING: Estonia. STUDY PARTICIPANTS: A random sample of Estonian residents aged 15-74 years (n = 997). MAIN MEASURES: Acceptability of PHC system (accessibility, the patient practitioner relations, amenities, and patient's preferences) and patients' satisfaction with primary care doctor. RESULTS: Of the 997 respondents, 46% were sufficiently informed about the transition to the general practitioner (GP)-based PHC system; however, 45% of respondents had not personally experienced any changes. Of the 997 persons interviewed, 68% were registered on the patient list of a GCP, and 62% of those who had health problems preferred to consult the primary care doctor first. The waiting time for an outpatient appointment was brief (0-2 days). Of the 997 respondents, 68% were satisfied with their primary care doctor. Satisfaction was dependent on: (i) how patients evaluated the competence of the physician; (ii) comprehensibility of doctor's explanations; and (iii) comfort of the clinic. The right of patients to choose their own primary care doctor and having sufficient information about the changes in PHC system had a positive influence on the level of satisfaction. CONCLUSIONS: Patients' opinions are important in the evaluation of PHC. To increase the level of satisfaction, people need to understand the nature and intent of the primary care reforms. Personal choice of primary care doctor and good patient-doctor relationships are important factors too. PMID- 11202605 TI - Quality of life in multiple sclerosis: development and validation of the 'RAYS' scale and comparison with the SF-36. AB - OBJECTIVE: To develop a self-administered rating scale for quantifying quality of life (QoL) in multiple sclerosis (MS) patients. METHODS: The RAYS scale items were derived from a source of 600 questions composed by our Centre's experts from commonly used instruments that assess physical, psychological, and social familial dimensions. Prior to finalization of the RAYS QoL, candidate items were administered to 15 health rehabilitation professionals. Clarity, importance, relevance and specificity were graded for each item by every professional independently. Items chosen for the final version were graded as good or excellent on all these aspects. The Medical Outcome Study Short Form-36 (SF-36) was used to compare health appraisal with the RAYS scale. RESULTS: Each of the three subscales of the RAYS covers a different dimension (physical, psychological, and social-familial) and each includes 15 self-report items scored from 1 (best) to 4 (worse), focusing on the preceding week. Validation was achieved through administration of the scale to 50 randomly selected MS patients and to 50 age, sex-, education- and family status-matched healthy controls. All RAYS dimensions among MS patients reached a Cronbach's coefficient alpha > 0.8. Mean values for all dimensions were greater in patients than in controls (P < 0.002). Patients scored below norms for the general population in the majority of the SF-36 subscales (on average 32% lower). Significant correlation was found between the two scales especially in the physical and social functioning subscales. CONCLUSION: The RAYS scale demonstrated high internal consistency and significant discriminative value, and is thus a suitable disease-specific tool for measuring QoL in MS. PMID- 11202606 TI - Coordination of care provision: the role of the 'handoff'. PMID- 11202607 TI - Actions of tachykinins within the heart and their relevance to cardiovascular disease. AB - Substance P and neurokinin A are tachykinins that are co-localized with calcitonin gene-related peptide (CGRP) in a unique subpopulation of cardiac afferent nerve fibers. These neurons are activated by nociceptive stimuli and exhibit both sensory and motor functions that are mediated by the tachykinins and/or CGRP. Sensory signals (e.g., cardiac pain) are transmitted by peptides released at central processes of these neurons, whereas motor functions are produced by the same peptides released from peripheral nerve processes. This review summarizes our current understanding of intracardiac actions of the tachykinins. The major targets for the tachykinins within the heart are the intrinsic cardiac ganglia and coronary arteries. Intrinsic cardiac ganglia contain cholinergic neurons that innervate the heart and coronary vasculature. Tachykinins can stimulate NK3 receptors on these neurons to increase their excitability and evoke spontaneous firing of action potentials. This action provides a mechanism whereby tachykinins can indirectly influence cardiac function and coronary tone. Tachykinins also have direct effects on coronary arteries to decrease or increase tone. Stimulation of NK1 receptors on the endothelium causes vasodilation mediated by nitric oxide. This effect is normally dominant, but NK2 receptor-mediated vasoconstriction can also occur and is augmented when NK1 receptors are blocked. It is proposed that these ganglion stimulant and vascular actions are manifest by endogenous tachykinins during myocardial ischemia. PMID- 11202608 TI - Characteristics of monkey tryptase purified from cheek pouch vascular tissues. AB - Tryptase purified from rat and dog tissues has been reported, although the characteristics of these enzymes are different from human tryptase. For pathophysiological studies of human tryptase, studies on species that have a similar tryptase to humans is needed. In this study, we purified monkey tryptase from cheek pouch vascular tissues using heparin affinity and gel filtration columns. The monkey tryptase, which had a molecular weight of 130 kDa by gel filtration, consisted of a tetramer of 33 kDa by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The N-terminal sequence showed high homology with tryptases from other species. The optimum pH and temperature were 7.5-9.0 and 25-40 degrees C, respectively. The enzyme was labile in high-KCl buffer, and the optimum KCl concentration was 0.1 M. The enzyme activity was completely inhibited by diisopropyl phosphorofluoridate and leupeptin but not by soybean trypsin inhibitor and alpha-antitrypsin. The enzyme hydrolyzed vasoactive intestinal peptide but did not affect angiotensin I, somatostatin and bradykinin. In the present study, we first isolated monkey tryptase from cheek pouch vascular tissues and showed that the characteristics of monkey tryptase are very similar to those of human tryptase. PMID- 11202609 TI - Effects of adrenergic alpha2-receptor agonists on urinary bladder contraction in conscious rats. AB - We investigated the effects of the adrenergic alpha2-receptor agonists clonidine, oxymetazoline and tizanidine on bladder contractions induced by infusing fluid into the bladders of conscious male rats. I.v. clonidine and oxymetazoline (both 0.01 to 0.1 mg/kg) caused bladder hyperactivity, expressed by shortening of the intercontraction interval. Tizanidine (0.1 mg/kg, i.v.) caused slight shortening of the intercontraction interval. The rank order of potency was clonidine = oxymetazoline >> tizanidine. Intrathecal (i.t.) injection of 10 microg clonidine and oxymetazoline, and intracerebroventricular (i.c.v) injection at 15 microg, produced almost the same pattern of bladder hyperactivity as that observed after i.v. injection of these drugs (0.03 mg/kg, i.v.). For all three administration routes of clonidine and oxymetazoline, i.v. idazoxan (0.3 mg/kg) exerted an inhibitory effect on the bladder hyperactivity induced by these drugs, except i.c.v injection of oxymetazoline. I.t. phenylephrine (30 microg) did not change the intercontraction interval. Although i.c.v. phenylephrine (15 microg) shortened the intercontraction interval, the potency was weaker than those of i.c.v. clonidine and oxymetazoline (15 microg). These results suggest that clonidine and oxymetazoline cause bladder hyperactivity by acting at adrenergic alpha2 receptors in the micturition centers of the lumbosacral and supraspinal regions. PMID- 11202610 TI - Effects of S-nitroso-cysteine on proteins that regulate exocytosis in PC12 cells: inhibitory effects on translocation of synaptophysin and ADP-ribosylation of GTP binding proteins. AB - S-Nitroso-cysteine (SNC) inhibits Ca2+-induced noradrenaline (NA) release from PC12 cells. Since SNC stimulated Ca2+ mobilization from intracellular Ca2+ pools and SNC-induced inhibition of NA release was not washed-out, SNC may modify exocytosis-related proteins that overcome Ca2+ mobilization. In the present study, we investigated the effects of SNC on exocytosis-related proteins in PC12 cells. Ionomycin stimulated NA release and increased the immunoreactivity of synaptophysin in the cytosol fraction. A 25-kDa synaptosome-associated protein (SNAP-25), which localizes to plasma membranes and vesicles, increased in the cytosol fraction after stimulation. The increases in these proteins by ionomycin were inhibited in PC12 cells treated with 0.6 mM SNC. Synaptobrevin and synapsin 1 in the cytosol fraction, and syntaxin and 43 kDa growth-associated protein in the membrane fraction were not affected by ionomycin or SNC. Incubation of each protein with SNC did not affect antibody immunoreactivity. [32P]ADP-ribosylation of GTP-binding proteins (Gi/Go) by pertussis toxin, but not Gs by cholera toxin, was inhibited in SNC-treated PC12 cells and by co-addition of SNC to the assay mixture. These findings suggest that 1) SNC inhibits translocation of vesicles containing synaptophysin and SNAP-25, and 2) SNC reacts with cysteine residues in Gi/Go, causing inhibition of ADP-ribosylation by pertussis toxin. PMID- 11202611 TI - Stimulation of high-affinity GTPase activity through group II metabotropic glutamate receptors in rat hippocampal and striatal membranes. AB - The stimulation of high-affinity GTPase activity through metabotropic glutamate receptors (mGluRs) was pharmacologically characterized with the use of a series of agonists for mGluRs in rat hippocampal and striatal membranes. The pharmacological profile of the response was almost identical to each other between both brain regions. Thus, the high-affinity GTPase activities were stimulated by several mGluR-related compounds with the following rank order of potency: (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) = (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (L-CCG-I) > L-glutamate = 2R,4R-4 aminopyrrolidine-2,4-dicarboxylate [(2R,4R)-APDC] > (S)-4-carboxy-3 hydroxyphenylglycine [(S)-4C3HPG] = 1S,3R-1-aminocyclopentane-1,3-dicarboxylate [(1S,3R)-ACPD] > (S)-3-carboxy-4-hydroxyphenylglycine [(S)-3C4HPG] = ibotenate. The negative logarithmically transformed EC50 (pEC50) values of these compounds in both brain regions were significantly correlated with those reported previously in the cerebral cortical membranes (N. Nishi et al., Br. J. Pharmacol., 130, 1664-1670, 2000). On the contrary, other reagents including a selective group I mGluRs agonist, (RS)-3,5-dihydroxyphenylglycine [(RS)-3,5 DHPG], and selective group III mGluRs agonists such as L(+)-2-amino-4 phosphonobutylate (L-AP4) and L-serine-O-phosphate (L-SOP) had little or no effects even at the highest concentration examined. Quisqualate was also a very weak agonist in both regions. These results indicate that mGluR-mediated high affinity GTPase activity derives from the Gi proteins associated with adenylyl cyclase inhibition through group II mGluRs, in particular the mGluR2 subtype, in rat hippocampal and striatal membranes. PMID- 11202612 TI - Enhancement of peptone-induced gastric acid secretion in streptozotocin-induced diabetic rats. AB - We compared the acid secretory response to peptone in normal and streptozotocin induced diabetic rats. Animals were injected with streptozotocin and used after 5 weeks of diabetes with blood glucose levels of >350 mg/dl. Under urethane anesthesia, 2 ml peptone solution (2-8%) was instilled in the stomach through an acute fistula every 30 min. Peptone increased acid secretion in a concentration dependent manner in normal rats, the maximal response being obtained at 8%. Likewise, the increased acid response was observed in diabetic rats, yet the maximal response observed at 4% was significantly greater than that in normal rats. In both cases, this response was inhibited potently by famotidine as well as YM-022 (a CCKB antagonist) and partially inhibited by atropine. Peptone increased luminal histamine and plasma gastrin levels in both normal and diabetic rats, and the former response was significantly greater in diabetic animals. The altered acid secretion and histamine output in diabetic rats were reverted by insulin treatment. Pentagastrin- but not histamine-induced acid secretion was also increased in diabetic rats. We conclude that peptone-induced acid secretion is increased in diabetic conditions. This phenomenon is insulin-dependent and associated with an enhanced release of histamine but not with an increased sensitivity of the parietal cells. PMID- 11202614 TI - Role of 5-HT1A receptors in a mouse passive avoidance paradigm. AB - The effect on memory processes of modulation of 5-HT1A receptor subtype was investigated in the mouse passive avoidance test. The administration of 5-HT1A receptor antagonists NAN-190 (1-(2-methoxyphenyl)-4-[4-2 phthalimmido)butyl]piperazine) and WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1 piperazinyl]ethyl]-N-2-pyridinyl-cyclohexanecarboxamide) produced a dose dependent amnesic effect comparable to that obtained with the well-known amnesic agents scopolamine and dicyclomine. Pretreatment with the 5-HT1A-receptor agonists 8-OH-DPAT ((+/-)-8-hydroxy-dipropylaminotetralin) and 5-CT (5 carboxamidotryptamine) dose-dependently prevented the amnesia induced by 5-HT1A antagonists, scopolamine, dicyclomine and exposure to an hypoxic environment. The antiamnesic effect exerted by 5-HT1A-receptor agonists was comparable to that produced by the nootropic drug piracetam and cholinesterase inhibitor physostigmine. At effective doses, neither 5-HT1A-receptor agonists nor 5-HT1A receptor antagonists produced any impairment of mouse motor coordination (rota rod test), spontaneous motility (Animex apparatus) and inspection activity (hole board). These results indicate that modulation of 5-HT1A-receptors appears to play an important role in the regulation of cognitive processes. PMID- 11202613 TI - Increase of calmodulin III gene expression by mu-opioid receptor stimulation in PC12 cells. AB - Calmodulin (CaM) is a principal multifunctional mediator of Ca2+ signaling in cells. It is reported that morphine increases CaM contents in mouse brain. However, the precise mechanism of CaM induction by morphine is unknown. We investigated the changes of CaM by opioid receptor stimulation in mRNA and protein levels. Expression of CaM was increased in dose- and time-dependent manners by morphine with RT-PCR assay in PC12 cells, and naloxone inhibited the effect of morphine. The expression was also increased with DAMGO (mu-opioid agonist), but not by DPDPE (delta) and U50488 (kappa). Northern blot analysis revealed that the CaMIII gene was responsive to morphine or DAMGO. CaM protein increased by DAMGO were distributed in both soluble and membranous fractions in the cells. Taken together, the data suggest that morphine induces the expression of CaMIII gene through mu-opioid receptor stimulation. PMID- 11202615 TI - Effects of nitric oxide on the vestibular functional recovery after unilateral labyrinthectomy. AB - The effects of nitric oxide on the vestibular function recovery following unilateral labyrinthectomy were studied. Male Sprague-Dawley rats treated with N omega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, were subjected to destruction of the unilateral vestibular apparatus and spontaneous nystagmus was observed. To explore the role of nitric oxide on the potassium current, the whole cell patch clamp technique was applied on isolated medial vestibular nuclear neurons. The frequency of spontaneous nystagmus that appeared in L-NAME-treated rats was higher and maintained longer than in control animals. Potassium currents in the isolated medial vestibular nucleus were inhibited by nitric oxide liberating agents, sodium nitroprusside and S-nitroso-N-acetylpenicillamine. After blockade of calcium dependent potassium currents by high EGTA (11 mM)-containing pipette solution, sodium nitroprusside did not inhibit the outward potassium currents. 8-Bromoguanosine 3,5-cyclic monophosphate, a membrane-permeable cGMP analogue, produced similar effects to inhibit the outward potassium currents as sodium nitroprusside. These results suggest that nitric oxide production after unilateral labyrinthectomy would help to facilitate vestibular compensation by inhibiting calcium-dependent potassium currents through increasing intracellular cyclic GMP, thereby increasing excitability in ipsilateral vestibular nuclear neurons. PMID- 11202616 TI - Role of Ca2+ mobilization in muscarinic receptor-mediated membrane depolarization in guinea pig ileal smooth muscle cells. AB - In single smooth muscle cells dispersed from guinea pig ileum, the muscarinic agonist carbachol (CCh) at 2 microM produced an oscillatory or sustained type of depolarization and at 100 microM, the latter type depolarization. Depletion of internal Ca2+ stores blocked the oscillatory response, but not the sustained responses to 2 microM and 100 microM CCh, although their decay after reaching the peak became faster. Blocking voltage-dependent Ca2+ channels (VDCCs) blocked both types of response to 2 microM CCh, but only slowed the initial rising phase of 100 microM CCh responses. Combination of Ca2+ store depletion and VDCC blockade abolished the responses to 2 microM CCh again and decreased those to 100 microM CCh in peak amplitude and persistency. Combination of Ca2+ store depletion with removal of extracellular Ca2+ markedly reduced or abolished the 100 microM CCh responses. The results suggest that muscarinic depolarization of the ileal cells requires Ca2+ mobilization for its generation and persistence; at weak muscarinic stimulation, both Ca2+ entry via VDCCs and Ca2+ release from internal stores may contribute to the Ca2+ mobilization; and under strong muscarinic stimulation, Ca2+ entry pathways resistant to VDCC blockers may also contribute to it. PMID- 11202617 TI - Enhancement of intracellular Cl- concentrations induced by extracellular ATP in guinea pig ventricular muscle. AB - We investigated effects of extracellular ATP on intracellular chloride activities ([Cl-]i) and possible contribution of the Cl--HCO3- exchange to this increase in [Cl-]i in isolated guinea pig ventricular muscles. The [Cl-]i and intracellular pH (pHi) were recorded in quiescent ventricular muscles using double-barreled ion selective microelectrode techniques. MgATP at a concentration higher than 0.1 mM, induced an increase in [Cl-]i, and this increase in [Cl-]i was dependent on the concentration of ATP but not on the concentration of magnesium ions present in the perfusion solution. NaADP, but not NaAMP, at a concentration of 0.5 mM induced a similar increase in [Cl-]i as that induced by MgATP. However, the NaADP induced increase in [Cl-]i was transient and gradually returned to the control level even though NaADP was continuously present. Furthermore, ATP also triggered a transient acidification of pHi, and both increases in [Cl-]i and intracellular H+ induced by ATP were prevented when preparations were pretreated with stilbene derivatives, SITS and DIDS, or perfused with a Cl--free solution. Our findings showed that the increased extracellular ATP concentrations might trigger an increase in [Cl-]i in ventricular muscles. In light of previous studies showing that cardiac ischemia induced increases in extracellular nucleotide concentrations and [Cl-]i in ventricular muscles, we propose that ischemia induced accumulation of ATP concentration in the extracellular space may be an important factor to trigger increment of [Cl-]i during ischemic conditions. PMID- 11202618 TI - The functional ratio of chymase and angiotensin converting enzyme in angiotensin I-induced vascular contraction in monkeys, dogs and rats. AB - Recently, a chymase-dependent angiotensin (Ang) II-forming pathway was found in human cardiovascular tissues, and the significance of this pathway in the pathogenesis of some cardiovascular diseases was suggested. The present study examined the ratio of angiotensin converting enzyme (ACE) to chymase-dependent Ang II formation in various isolated vessels from monkeys, dogs and rats. In all of the examined vessels, the addition of KCl at a concentration of 50 mM could induce a maximal contraction. Except for monkey coronary artery and rat renal and femoral artery, the addition of Ang I could induce transitory contractions, whereas the force of contractions in these vessels was quite different. The sensitivity to Ang II in these vessels was similar to that for Ang I. In monkey gastroepiploic and mesenteric arteries, about 70% of the Ang I-induced contraction was suppressed by chymase inhibition, while it was suppressed about 50% in monkey renal, femoral and carotid arteries. In dog renal arteries, about 65% of the Ang I-induced contraction was suppressed by chymase inhibition, while it was suppressed by about 30% in other dog arteries. In contrast, in all rat arteries, Ang I-induced contractions were completely suppressed by treatment with ACE inhibitor alone. We concluded that regional differences in the response to Ang I exist in vascular tissues, and the ratio of ACE- to chymase-dependent Ang II formation is different in the various vessels. PMID- 11202619 TI - Fasting exacerbates acute pancreatitis by occlusion of the common bile duct in rats. AB - We examined the effects of fasting and non-fasting on gallstone-related acute pancreatitis by the occlusion of the common bile duct (OCD). We prepared a rat OCD-induced pancreatitis model under both fasting and non-fasting conditions, and we measured amylase activity in ascites as well as production of inflammatory cytokines and chemokines. We also examined the pathology of the pancreas, myeloperoxidase (MPO) activity in some tissues and mortality rates. In the fasted OCD group, ascites containing a large amount of amylase, interleukin 1beta (IL 1beta), interleukin 6 (IL-6), and cytokine-induced neutrophil chemoattractant-1 (CINC-1) as well as marked hemorrhage and necrosis of the pancreatic acinar cells were observed. Pulmonary MPO activity increased 3.4-fold compared to the control group. In the non-fasted OCD group, there was no development of ascites. Slight necrosis of acinar cells and slight increases in pulmonary MPO activity were observed. In addition, in the fasted OCD group, the cumulative mortality rate was 50% 6 days after ligation. However, in the non-fasted OCD group, none of the animals died. These results suggest that gallstone-related severe pancreatitis depends on fasting-related structural and/or functional changes in the pancreas. Moreover, increased production of inflammatory cytokines and chemokines in ascites under fasting condition may be involved in multiple organ failure resulting from severe acute pancreatitis. PMID- 11202620 TI - Itch-associated responses of afferent nerve innervating the murine skin: different effects of histamine and serotonin in ICR and ddY mice. AB - To assess the itch-associated response of primary afferents innervating the murine skin in vivo, dose-response curves and time-courses for itch-scratching and cutaneous nerve firing responses to intradermal injections of pruritogens (histamine and serotonin) were compared in ICR and ddY mice. Serotonin increased the itch-scratch response and cutaneous nerve firing in either ICR or ddY mice. Histamine increased these two responses in ICR, but not ddY, mice. The dose response curves and time-courses for serotonin- and histamine-induced nerve firing were similar to those for the itch-scratch response. The results suggest that cutaneous nerve firing evoked by peripherally given pruritogens includes the itch-associated response. PMID- 11202621 TI - The effects of melatonin in glutamate-induced neurotoxicity of rat cerebellar granular cell culture. AB - In the present study, melatonin was tested in subsequent doses in glutamate induced neurotoxicity in cerebellar granular cell culture of rat pups. Glutamate at 10(-7) M was found to induce neuronal cell death. The dead cell score was 2.75+/-0.7 in the control, while it was found to be 35.12+/-1.8 in the glutamate administered group (P<0.0001). Melatonin very potently blocked glutamate neurotoxicity at all doses tested, with 10(-3) M, the highest dose tested, being the most effective. Glutamate may exert a neuroprotective effect by blocking one or more steps of the oxidation cascade in neurons and this effect may be blocked by melatonin. PMID- 11202622 TI - Effect of hydrogen peroxide on guinea pig nasal mucosa vasculature. AB - The effect of hydrogen peroxide (H2O2) on guinea pig nasal mucosa vasculature was studied by in vitro assay. H2O2 elicited relaxation of guinea pig nasal mucosa strips precontracted with phenylephrine in a concentration-dependent manner. The relaxant response to H2O2 was abolished in the presence of catalase. Preincubation of the strips with N(G)-nitro-L-arginine methyl ester or methylene blue significantly attenuated the relaxant responses elicited by H2O2. Fluorescence caused by DAF-2 DA, a fluorescence indicator for nitric oxide, was observed along the nasal mucosa vasculature in response to H2O2. These results suggest that H2O2 induced relaxation of the guinea pig nasal mucosa vasculature and that this relaxation is mediated by the NO/cGMP pathway. PMID- 11202623 TI - Ca2+-Sensitization of contraction in the h1 calponin-deficient smooth muscle. AB - Role of h1 calponin on Ca2+-sensitivity of smooth muscle contraction was investigated using h1 calponin gene-deficient mice (CP -/-) and wild type mice (CP +/+). PGF2. induced a comparable force in intact aorta of CP +/+ and CP -/-. DPB showed similar effects to PGF2alpha. In membrane-permeabilized ileal smooth muscle, PDBu enhanced Ca2+-sensitivity of contraction comparably in CP +/+ and CP -/-. GTPgamma-S showed similar effects. Our results suggest that h1 calponin does not regulate Ca2+-sensitivity in the contractile mechanism of smooth muscle. PMID- 11202624 TI - [6 years with Annali Italiani di Medicina Interna]. PMID- 11202625 TI - Psychological constructs associated with emotional blood pressure response and white coat phenomenon. AB - Some hypertensive and non-hypertensive subjects have a striking blood pressure response to a medical environment (white coat phenomenon), although it is unlikely that its presence, degree, and duration can be routinely predicted. Despite the common observation that "anxious" patients may present with this reaction when a physician measures their blood pressure, no psychological variables have thus far been linked to white coat phenomenon in formal analyses. Ambulatory blood pressure monitoring is a useful tool to disclose the phenomenon since it allows precise evaluation of repeated blood pressure measurements outside the medical environment. To investigate the possible relationship between psychological profile and white coat phenomenon, we have planned to administer a series of psychometric tests to 120 subjects undergoing ambulatory blood pressure monitoring. The present data are derived from an analysis of the first set of 70 patients. Thirty-four subjects who presented with white coat phenomenon (defined as office blood pressure elevated by at least 15% over the mean 24-hour ambulatory blood pressure value) and 36 comparable subjects who did not have this reaction underwent a series of psychometric tests evaluating cognitive behavior, hostility, cynicism, anger, anxiety state, coping ability and strategies, and quality of life. Of the various psychometric tests, the scores of three relevant scales (healthcare-related fears, mental efficiency and behavioral disengagement) were significantly higher in the group of patients with white coat phenomenon, while in both groups, emotional instability was higher than the clinical cut-off point. There were no significant differences between the two groups regarding signs and repression of anger (anger-out and anger-in), cynicism, hostility, or anxiety state. Our data seem to indicate that the subjects most likely to show an overt blood pressure increase in the medical environment are those who evidence healthcare-related fears and emotional instability but are not necessarily anxious. They exhibit high coping skills in cognitive resolution of stressing situations (such as blood pressure measurement) but do not combine these strategies with an adequate behavioral response and do not feel that behavioral involvement is necessary for the management of their clinical condition. PMID- 11202626 TI - [3-year-survival and quality of life after out-of-hospital heart arrest]. AB - Although the long- and short-term aspects of the outcome of advanced cardiopulmonary resuscitation on patients have been studied to evaluate the percentage of survival up to the moment of discharge from hospital, little information has been published concerning the patients' long-term quality of life. In order to verify the efficiency of our group we retrospectively evaluated 468 subjects admitted to the Emergency Room of Rho Hospital (Milan, Italy) for out-of-hospital cardiac arrest that had occurred over a 90-month period. We studied the correlations between some variables: epidemiological (sex and age), objective (time required for advanced cardiopulmonary resuscitation and type of arrhythmias in the Emergency Room) and instrumental (left ventricular ejection fraction) and post-discharge survival. We also considered the state of health of the survivors by means of a questionnaire on their quality of life. Our data show that: a) 10.25% of the patients were discharged alive; b) younger men (< 65 years old) admitted with a ventricular fibrillation (p = 0.01) and those who had undergone advanced cardiopulmonary resuscitation for less than 25 min (p = 0.001) had a better survival rate at 3 years from discharge; c) 64% of the survivors have a satisfactory quality of life; d) younger age (p = 0.01) and cardiac left ventricular ejection fraction (> 40%) (p = 0.05) are positive predictors for future work capacity. In conclusion, we believe that the critical moment following advanced cardiopulmonary resuscitation is hospitalization because after discharge survival percentage abruptly increased from 10.25 to 65%. PMID- 11202627 TI - Apparently dominant transmission of a recessive disease: deficiency of factor VII in Iranian Jews. AB - In inherited disorders transmitted as autosomal recessive traits the children of affected individuals are usually asymptomatic and phenotypically normal because they are heterozygous for the defect. In an Iranian Jewish family with moderately severe deficiency of coagulation factor VII (an autosomal recessive bleeding disorder) the son of an affected woman was also affected. DNA analysis of the factor VII gene showed that this unusual situation was due to the fact that he inherited an abnormal allele with the Ala244Val missense mutation from both the homozygous mother and the heterozygous father. The parents, although not overtly consanguineous, belong to the same ethnic group of Iranian Jews, among whom this factor VII gene mutation reaches high frequencies (between 2 and 3%) in the heterozygous state. PMID- 11202628 TI - [D-dimer in the year 2000: current data and new perspectives]. AB - D-dimer is a product of cross-linked fibrin degradation by the fibrinolytic system. It has been shown to be highly sensitive and moderately specific for venous thromboembolic disease. Thus, the most common clinical use of D-dimer relates to its negative predictive value for deep vein thrombosis and pulmonary embolism. Diagnosis, however, should not be based solely on this parameter, and an integrated strategy that combines clinical approach (pre-test probability), a non-invasive test (ultrasonography or lung scan) and D-dimer assay is highly recommended. Over the last years a number of studies have demonstrated that D dimer may also enable the prediction of the complications of atherothrombosis inasmuch as the data available suggest a significant association of D-dimer with the risk of coronary artery disease independent of classic risk factors. Moreover, elevated plasma D-dimer seems to be a marker of a systemic prothrombotic state, and anticoagulation can normalize its levels. However, further studies are needed to assess whether or not this parameters is of clinical value to predict or prevent arterial thrombotic events in the single patient. PMID- 11202629 TI - [Morphologic study of the microcirculation in connective tissue diseases]. AB - Capillaroscopy is a non-invasive diagnostic test used to study microvascular abnormalities which are present in many disorders, particularly some rheumatic pathologies, such as connective tissue diseases. In systemic sclerosis, capillaroscopy allows detection of pathognomonic microvascular alterations. In other connective tissue diseases, including systemic lupus erythematosus, dermatopolymyositis, undifferentiated connective tissue diseases, and mixed connective tissue disease, the capillaroscopic patterns, although non-specific, can provide a valid support for the diagnosis. In Raynaud's phenomenon, capillaroscopy enables detection of early microvascular abnormalities that are useful for preclinical diagnosis of secondary Raynaud's phenomenon. PMID- 11202630 TI - Antithrombotic drugs for the secondary prevention of ischemic stroke. AB - On the assumption that antithrombotic drugs are able to reduce the incidence of any vascular event independently of where it first occurs, they are used for the secondary prevention of arterial vascular disease in different locations. The Antiplatelet Trialists' Collaboration meta-analysis has shown that the net benefit of antiplatelet drugs in the prevention of stroke, acute myocardial infarction and vascular death is about the same for patients with prior stroke or prior myocardial infarction. Most of the trials included in the Antiplatelet Trialists' Collaboration meta-analysis used aspirin, which was shown to lower the risk of stroke, myocardial infarction, and vascular death in patients with a history of transient ischemic attack or stroke. Aspirin should be given to patients operated on for symptomatic carotid stenosis and should be considered for asymptomatic patients. In a comparative study ticlopidine (500 mg) vs aspirin (650 mg), ticlopidine reduced the relative risk of vascular events by 9% and of recurrent stroke by 21%. When clopidogrel (75 mg) was compared with aspirin (325 mg), a 7.3% relative risk reduction was seen in the stroke group (6431 patients) of the CAPRIE study; a reduction in hemorrhagic events, especially in gastrointestinal bleeding, was also seen. At variance with previous studies, the ESPS-2 showed an advantage when dipyridamole (400 mg) was added to aspirin (50 mg). Oral anticoagulants are more effective than aspirin in the prevention of cardioembolic stroke in patients with atrial fibrillation. The higher efficacy of indobufen with respect to aspirin in this particular setting needs confirmation. Inhibition of thrombosis may be one of the mechanisms explaining the effect of statins in reducing both stroke and cardiac events in high-risk patients. PMID- 11202631 TI - [Meningococcal meningitis in the adult complicated by cutaneous necrosis: description of a clinical case]. AB - Meningitis and meningococcal sepsis are emergency conditions associated with high mortality. The outcome is worsened by the onset of disseminated intravascular coagulation. This may present, particularly in children, with the clinical picture of purpura fulminans, characterized by extensive necrotic-hemorrhagic skin lesions, ischemia of the extremities and multiorgan failure. It has been observed that depletion of coagulation inhibitors, particularly protein C, plays a key role in the development of this severe complication. We describe the case of a woman who presented in the Emergency Room with signs of meningitis, drowsiness, hypotension and petechie. Bacterioscopic examination of the cerebrospinal fluid evidenced characteristic gram-negative diplococci. Laboratory data disclosed initial disseminated intravascular coagulation with low levels of proteins C and S. Following intravenous infusion of antibiotics, fluids and fresh frozen plasma, the patient's condition rapidly improved. However, multiple skin lesions appeared on her fingers, toes and heels. It is likely that the infusion of coagulation inhibitors contained in fresh frozen plasma, prevented evolution to full-blown purpura fulminans. The first choice treatment for purpura fulminans in meningococcal sepsis is infusion of protein C concentrate, which is not, however, currently available on the market. PMID- 11202632 TI - Liquorice-induced sodium retention. Merely an acquired condition of apparent mineralocorticoid excess? A case report. AB - Excessive ingestion of liquorice may result in sodium retention, hypertension, hypokalemia, and suppression of renin and aldosterone. Similarities between liquorice-induced effects and congenital apparent mineralocorticoid excess have recently been emphasized, as in both conditions, reduced activity of the enzyme 11 beta-hydroxysteroid dehydrogenase type 2 allows cortisol to act as a potent mineralocorticoid. We report a case of generalized edema without any increase in blood pressure, with biochemical and hormonal features of apparent mineralocorticoid excess, in a young woman who had been ingesting substantial amounts of liquorice for several years. Liquorice-induced wide-spread edema without hypertension in our patient, as well as in a few other cases previously reported, and the more common occurrence of edema associated with hypertension challenge the current explanation of liquorice syndrome as a purely acquired apparent mineralocorticoid excess. Indeed, in both congenital apparent and true mineralocorticoid excess, edema is typically absent, as a result of the sodium escape phenomenon. As pressure-natriuresis may be an essential mechanism accounting for the sodium escape phenomenon, some component of liquorice could partially or completely oppose the circulatory response that converts liquorice induced sodium retention into blood pressure elevation. In patients with unexplained generalized edema and hypokalemia without hypertension, liquorice ingestion should be carefully investigated and the renin-aldosterone system should be assayed. PMID- 11202633 TI - Tetanus-like syndrome secondary to metoclopramide administration. AB - A case of metoclopramide-induced pseudotetanus in a 24-year-old woman is described. Symptoms included flexor spasms of the neck muscles, neck pain, left deviation of the lower jaw and tongue protrusion. Tetanus was initially suspected. Mydriasis, hyperhydrosis and clinical observation indicated that this syndrome could be caused by metoclopramide taken for gastrointestinal symptoms. Orphenadrine hydrochloride, diazepam and ketoprofen completely resolved the symptoms. Pseudotetanus presents in many different ways, and it is sometimes very hard to distinguish it from infective tetanus, which is very difficult to diagnose. Physicians using metoclopramide should be aware of its adverse effects and how to treat them. PMID- 11202634 TI - Severe postpartum hypertension and reversible cerebral angiopathy associated with ergot derivative (methergoline) administration. AB - A 36-year-old woman (gravida 2, para 2) delivered a healthy child by cesarean section at the 37th week of an unremarkable gestation. Blood pressure remained within normal range throughout the pregnancy, surgery, and for the 9 following days. On day 10, about 36 hours after the initiation of oral methergoline to suppress lactation, the patient complained of severe posterior headache, flashing scotomata, hypertension, tonico-clonic seizures and then homonymous left hemianopsia and hemiparesis. Blood pressure monitoring confirmed intermittent and severe hypertension. Angiography demonstrated diffuse narrowing of the small and medium cerebral arteries. Transcranial Doppler ultrasound examination disclosed a bilateral increase in mean flow velocity. Progressive normalization of blood pressure, obtained with labetalol and oral clonidine, was accompanied by amelioration of the neurological deficits until a complete recovery and normalization of transcranial Doppler flow velocity occurred. This case provides further evidences that hypertension might play a major pathogenetic role in reversible cerebral angiopathy. Some ergot derivatives (including methergoline) might trigger the initial rise in blood pressure. PMID- 11202636 TI - [Resolution of the Ninth (LXXII)Session of the General Meeting of the Russian Academy of Medical Science (RAMS) on Man and Microorganisms. Health and Disease]. PMID- 11202635 TI - [Molecular epidemiology as a new research area in the study of natural and focal infections]. PMID- 11202637 TI - [Tuberculosis in the Russian Federation is a problem of state significance]. PMID- 11202639 TI - [Efficiency of international tuberculosis control programmes in the Tomsk Region]. AB - Since 1994, international tuberculosis control programmes in the have been implemented in the Tomsk Region by using advanced experience in Russian phthisiology and foreign medicine by attracting many specialists of the British "Merlin" agency (London), New York Health Institute (USA). A program is financed from different funds of other countries (KNOW HOW, J. Soros, EU, British government, WHO) and from regional sources. The phthisiological doctrine has been changed, all tuberculosis control services in the region has been substantially restructured and integrated. A new concept of tuberculosis diagnosis and treatment has been developed. DOTS and DOTS-PLUS which form the present strategy of WHO to control this disease throughout the world have been developed. PMID- 11202638 TI - [Present-day aspects (diagnosis, clinical course and treatment) of acute progressive pulmonary tuberculosis]. AB - A total of 103 patients with acute progressive pulmonary tuberculosis whose age ranged from 18 to 60 years were examined. Caseous pneumonic, infiltrative caseous, disseminated, and rapidly progressive fibrocavernous tuberculosis was found in 45.6, 17.5, 16.5, and 20.4% of cases, respectively. The clinical picture was characterized by its acute onset with significant intoxication syndrome. Moreover, all the patients had respiratory and immunological failure, varying disseminated intravascular coagulation syndrome, non-specific bronchopulmonary infection; some presented with pulmonary hemorrhage, spontaneous pneumothorax and pleural empyema. The sputum smear test was positive in all the patients. If there was no evidence for drug resistance, patients had a 4-month regimen using isoniazid, rifampicin, pyrazinamide, ethembutol, and kanamycin. In the subsequent 10-12 months, isoniazid, rifampicin, and ethambutol were given. The patients with multidrug resistant tuberculosis were administered protionamide, ofloxacin, amikacin, supplemented by pyrazinamide and ethambutol. The combined chemotherapy could stop bacterial isolation in more than 80% of patients, make the process stable, and prepare them for planned surgical treatment. When complications occurred and the disease was in steady progress, salvage operations were made, which was the only possible way of preventing the progression of disease at times and of saving life in the patient. PMID- 11202640 TI - [Microorganisms and food. Risk and benefits]. PMID- 11202641 TI - [Morpho-functional changes of surfactant system in pulmonary tuberculosis]. AB - A complex study of different cellular and extracellular surfactant elements in the dynamics of the spontaneous course of generalized tuberculosis was made in 240 guinea-pigs and 77 patients with different forms of active pulmonary tuberculosis by using electron microscopy, biochemistry, and physical chemistry. A diagnostic scheme was proposed for life-time assessment of surfactant in bronchoalveolar lavage specimens. Three degrees of changes in surfactant were identified; 1) adaptive rearrangement of its elements developing in local surfactant damages; 2) significantly impaired type 2 alveolocyte production of surfactant, which affects its biochemical composition and capacity of forming characteristic structures; 3) common morphological, biochemical, surface-active signs of surfactant decompensation, profound metabolic disturbances, alveolar epithelial destruction with cleared alveolocytes found in the lavage. PMID- 11202642 TI - [Role of xenobiotic biotransformation enzymes in susceptibility to bronchial asthma and in formation of its clinical phenotypic features]. AB - The paper shows the impact of some mutations of CYP1A, GSTM1, GSTT1, and NAT2 genes and different combinations of alleles of these genes on susceptibility to bronchial asthma and its clinical features. Passive smoking modulates these relationships. PMID- 11202643 TI - [Role of biological defects in formation and development of bronchial asthma and potentialities of premorbid diagnosis]. AB - The paper considers bronchial asthma as a polygenic disease. It presents some data available in the literature on the role of genetic disorders in the development of atopic states and the authors' own findings of various biological defects detected in apparently healthy blood relatives of patients with bronchial asthma. It is concluded that premorbid diagnosis is of importance in high risk persons. PMID- 11202644 TI - [Genomic medicine in the solution of pulmonological problems]. AB - Main points of the new direction genomic medicine and its applications to solution of pulmonological problems are outlined. Information on the molecular epidemiology of cystic fibrosis and bronchial asthma is presented. The frequency of major cystic fibrosis gene mutations and bronchial asthma candidate gene polymorphisms was defined in Siberian populations. The familial case histories of patients with bronchial asthma were used to assess the contribution of interleukine (IL4, IL5, IL9) and nitric oxide synthase (NOS3) genes to susceptibility to bronchial asthma. PMID- 11202647 TI - [Asepsis and antisepsis]. PMID- 11202645 TI - [Ten-year activities of the Faculty for Training of Scientific and Pedagogical Personnel, I.M. Sechenov Moscow Medical Academy]. AB - With the assistance and direct participation of the Presidium of the Russian Academy of Medical Sciences, the I. M. Sechenov Moscow Medical Academy has developed and introduced an unique elitist educational system to train of scientific and pedagogical staff at the pre- and postdiploma training stages on the basis of their close relationships and continuity, within whose framework a specially designed faculty has been successfully operating for 10 years. The basic principle that ensures its effective activity and solution of many didactic problems is the individualization and differentiation of an educational process by using a great diversity of reserves and organizational forms. The created system is unique in Russian and foreign practice. It improves the quality of scientific and pedagogical staff training, promotes more effective creation of staff reserves for the departments of higher educational establishments and research institutes of the Russian Academy of Medical Sciences and the Ministry of Health of the Russian Federation. PMID- 11202646 TI - [Analysis of the annual open Russian competition for the best scientific student work in medical science]. AB - For over 5 years, the I. M. Sechenov Moscow Medical Academy has been the basic Institute for holding the open Russian competition for the best scientific student work in medical sciences. The Academy has developed a methodological basis of this competition, which allowed the practical use of its organizational forms by the areas of informational support, evaluation of works, awards, office work. The authors' skills in presentation have become an original educational component in addition to usual expert estimation of works and afforded to obtain knowledge of progress in basic science and different problems in the organization of researches. The original competition organizing system has raised the popularity of the competition and the annual number of participants from different medical institutes and stimulated youth's interest in researches. PMID- 11202648 TI - Pesticide effects on freshwater zooplankton: an ecological perspective. AB - The effects of pesticides on zooplankton are reviewed and their ecological significance is discussed. Toxicity is shown to vary depending on animal species, genotype, life stage, and size at birth. Natural stresses such as food shortage, oxygen depletion and odors of potential predators can also affect toxicity. Populations in the growth phase are vulnerable to pesticides but have the potential to recover rapidly from the damage. Pesticides may affect the population dynamics by controlling individual survival and reproduction, and by altering the sex ratio. Furthermore, toxic chemicals may control predation risk by changing swimming behavior and body morphology, and this in turn influences the population dynamics. Many zooplankton display morphological and behavioral responses to predators when exposed to their odor-producing chemicals. However, pesticides induce a maladaptive response to predator odor, and this poses an ecological risk. The following patterns are recognized as effects of pesticides at the community and ecosystem levels: (1) induction of dominance by small species; (2) an increase of species richness and diversity; and (3) elongation of the food chain and reduction of energy transfer efficiency from primary producers to top predators. PMID- 11202649 TI - Comparative metabolism of phenanthridine by carp (Cyprinus carpio) and midge larvae (Chironomus riparius). AB - Abiotic transformation of azaarenes in the environment has been analysed extensively, but metabolism is less well described. To further elucidate preliminary observations of interspecific differences in azaarene metabolism by aquatic organisms, phenanthridine biotransformation by midge larvae and carp was studied. In both experiments, 6(5H)-phenanthridinone (phenanthridone) was found as an important metabolite. The fish were clearly capable of metabolising phenanthridine, but in the midge experiment the metabolite was principally formed by bacteria growing on the food and not by the midges. Phenanthridone itself was further degraded to non-observed compounds in both experiments, due to bacteria and midges acting together in the midge experiment, and by carp in the fish experiment. Internal concentrations of phenanthridine and phenanthridone were non detectable in the midge larvae, but concentrations of both compounds in carp organs suggested a major role of bile and liver. Since phenanthridone did not account for all phenanthridine loss, it was suggested that, apart from phenanthridone degradation, other metabolic pathways may play a role. This study clearly demonstrates the importance of interspecies differences in metabolism, which should not be neglected in risk assessment. PMID- 11202651 TI - Increased retention of polycyclic aromatic hydrocarbons in soils induced by soil treatment with humic substances. AB - The analytical recovery of a mixture of polycyclic aromatic hydrocarbons (PAHs) was determined from a soil before and after oxidation with hydrogen peroxide, and subsequently treated with increasing amounts of an exogenous humic acid and subjected to different incubation periods. The release of PAHs from soil depended on the specific structure and physico-chemical properties of each PAH, and increased with additions of exogenous humic materials for both the oxidized and non-oxidized soil as well as with time of PAH permanence in soil. PAH recoveries were lower in the non-oxidized soil, thereby revealing the importance of native organic matter in increasing PAH retention in soils. This study shows that mobility of PAHs in soils can be controlled by soil conditioning with humic substances. PMID- 11202650 TI - Accumulation of silver in the liver of three species of pinnipeds. AB - Silver in the three species of pinnipeds [northern fur seal (Callorhinus ursinus), Steller sea lion (Eumetopias jubatus), and harbor seal (Phoca vitulina)] caught in the North Pacific Ocean were analyzed using inductively coupled plasma-mass spectrometry, in order to understand accumulation and distribution of silver in pinnipeds. In northern fur seals, relatively high concentrations of silver were observed in the liver and body hair. Some 70% of the silver burden was concentrated in the liver. Hepatic silver concentrations were significantly correlated to age in northern fur seals (r = 0.766, P < 0.001, n = 49) and Steller sea lions (r = 0.496, P < 0.01, n = 28). Levels of silver concentrations per wet weight (microgram g-1) in the three pinnipeds ranged from 0.04 to 0.55 for northern fur seals, from 0.1 to 1.04 for Steller sea lions and from 0.03 to 0.83 for harbor seals. Silver concentrations in liver for all pinnipeds were significantly correlated with mercury, and selenium (P < 0.001). Molar ratios between silver to selenium approximated 1:180 in northern fur seals, 1:120 in Steller sea lions, and 1:60 in harbor seals. The silver-mercury molar ratios were approximately 1:170 in northern fur seals, and 1:80 both in the other species. Increase in silver accumulation in the liver was caused by the retention in nuclei and mitochondria fraction together with mercury and selenium in the cells of northern fur seals. PMID- 11202652 TI - Exposure to heavy metals and infectious disease mortality in harbour porpoises from England and Wales. AB - We investigate whether long-term exposure to heavy metals, including immunosuppressive metals like mercury (Hg), is associated with infectious disease in a wild cetacean. Post-mortem investigations on 86 harbour porpoises, Phocoena phocoena, found dead along the coasts of England and Wales revealed that 49 of the porpoises were healthy when they died as a consequence of physical trauma (most frequently entrapment in fishing gear). In contrast, 37 porpoises died of infectious diseases caused by parasitic, bacterial, fungal and viral pathogens (most frequently pneumonia caused by lungworm and bacterial infections). We found that mean liver concentrations of Hg, selenium (Se), the Hg:Se molar ratio, and zinc (Zn) were significantly higher in the propoises that died of infectious disease compared to healthy porpoises that died from physical trauma. Liver concentrations of lead (Pb), cadmium (Cd), copper (Cu) and chromium (Cr) did not differ between the two groups. Hg, Se, and the Hg:Se molar ratio were also positively correlated with age. The association between Zn concentration and disease status may result from Zn redistribution in response to infection. Further work is required to evaluate whether chronic exposure to Hg may have presented a toxic challenge to the porpoises that succumbed to infectious disease. PMID- 11202653 TI - Nutrient losses by surface run-off following the application of organic manures to arable land. 1. Nitrogen. AB - Research was conducted on nitrogen (N) surface run-off losses following organic manure applications to land, utilising a purpose-built facility on a sloping site in Herefordshire under arable tillage. Different rates and timing of cattle slurry, farmyard manure and inorganic N and phosphorus (P) fertiliser were compared, over a 4-year period (1993-97). P losses from the same studies are reported in a separate paper. The application of cattle slurries to the silty clay loam soil increased the loss of solids and NH4(+)-N in surface water flow compared to control plots receiving inorganic fertiliser only, or no treatment, but had little effect on NO3(-)-N losses by this route. Results were consistent with other observations that rainfall events immediately after manure applications are particularly likely to be associated with nutrient run-off losses. Losses via subsurface flow (30 cm interflow) were consistently much lower than via surface water movement and were generally unaffected by treatment. Increasing slurry application rate and, in particular, slurry solids loading, increased solids and NH4(-)-N losses via surface run-off. The threshold, above which the risk of losses via surface run-off appeared to be greatly increased, was ca. 2.5-3.0 t/ha slurry solids, which approximates to the 50 m3/ha limit suggested for slurry within UK 'good agricultural practice'. Sealing of the soil surface by slurry solids appears to be a possible mechanism by which polluting surface run-off may occur following slurry application on susceptible soils. Total losses of NH4(+)-N and NO3(-)-N during the 4-year monitoring period were insignificant in agronomic terms, but average soluble N concentrations (NH4(+)-N + NO3(-)-N) in run-off, ranging from ca. 2.0 mg/l, up to 14.0 mg/l for the higher rate slurry treatments. Peak concentrations of NH4(+)-N > 30 mg/l, are such as to be of concern in sensitive catchments, in terms of the potential for contribution to accelerated eutrophication and adverse effects on freshwater biota. PMID- 11202654 TI - Nutrient losses by surface run-off following the application of organic manures to arable land. 2. Phosphorus. AB - Phosphorus (P) surface run-off losses were studied following organic manure applications to land, utilising a purpose-built facility on a sloping site in Herefordshire under arable tillage. Different rates and timing of cattle slurry, farm yard manure (FYM) and inorganic nitrogen (N) and P fertiliser were compared, over a 4-year period (1993-97). N losses from the same studies are reported in a separate paper. The application of cattle FYM and, especially slurry, to the silty clay loam soil increased both particulate and soluble P loss in surface water flow. Losses via subsurface flow (30 cm interflow) were consistently much lower than via surface water movement and were generally unaffected by treatment. Increased application of slurry solids increased all forms of P loss via surface run-off; the results suggested that a threshold for greatly increased risk of P losses via this route, as for N, occurred at ca. 2.5-3.0 t/ha solids loading. This approximates to the 50 m3/ha application rate limit suggested for slurry within UK 'good agricultural practice'. The studies also provided circumstantial evidence of the sealing of the soil surface by slurry solids as the major mechanism by which polluting surface run-off may occur following slurry application on susceptible soils. Losses of total and soluble P, recorded for each of the 4 years of experiments, reached a maximum of only up to 2 kg/ha total P (TP), even after slurry applications initiating run-off. Whilst these losses are insignificant in agronomic terms, peak concentrations of P (up to 30,000 micrograms/l TP) in surface water during a run-off event, could be of considerable concern in sensitive catchments. Losses of slurry P via surface run off could make a significant contribution to accelerated eutrophication on entry to enclosed waters, particularly when combined with high concentrations of NO3(-) N. Restricting slurry application rates to those consistent with good agronomic practice, and within the limits specified in existing guidelines on good agricultural practice, offers the simplest and most effective control measure against this potentially important source of diffuse pollution. PMID- 11202655 TI - Effects of development time, biomass and ferromanganese oxides on nickel sorption by stream periphyton. AB - Procedurally defined periphyton frequently includes substantial quantities of hydrous iron (Fe) and manganese (Mn) oxides. As these oxides are strong sorbers of heavy metals, their presence may complicate estimation of metal bioaccumulation by periphyton. We examined the relationship between nickel (Ni) sorption and the development time, biomass, and Fe and Mn oxide content of stream periphyton. Development time, the time during which periphyton accrued on submerged tile substrata, was used to provide variation in biomass, Fe and Mn levels. Stream periphyton from four development times was exposed to Ni for 2 h in the laboratory, and then ashed. Development time was significantly associated with ash-free dry mass (AFDM), Fe and Mn levels (ANOVA, P < or = 0.003). Ni extracted by a mild reductant (hydroxylamine hydrochloride) was significantly associated with development time, and with AFDM, Fe and Mn levels (linear models, P < or = 0.0002). A subsequent acid digestion yielded similar associations with the same variables (linear models, P < or = 0.0001). For both extractions, AFDM was significantly and positively correlated with Fe (r = 0.68 and 0.89) and with Mn (r = 0.77 and 0.93) (Spearman rank, P < or = 0.005). These data demonstrate the importance of periphyton development time in influencing both metal sorption and levels of biomass and ferromanganese oxides. The data also suggest that metal contaminant levels in periphyton should not be attributed automatically to biotic sorption. Periphyton metal-accumulation studies conducted where ferromanganese oxide concentrations are elevated should address the potential metal-sorbing roles of Fe and Mn oxides within the periphyton matrix. PMID- 11202656 TI - Immunotoxicity risks associated with land-treatment of petrochemical wastes revealed using an in situ rodent model. AB - Land-treatment of petrochemical wastes is a widely used method to dispose of hazardous and non-hazardous waste by biodegradation. However, no comprehensive assessment of the impact of such disposal techniques on terrestrial ecosystems has been conducted. Despite the presence of suspected immunotoxicants in the soil, wild rodents frequently reside on these waste sites after closure or abandonment. We explored the seasonal sensitivity of the immune system of the hispid cotton rat (Sigmodon hispidus) to in situ exposures on sites land-treated with petrochemical wastes. Animals were monitored on five contaminated land treatment sites and five ecologically matched-reference sites in Oklahoma, USA, over two seasons (summer and winter). Most hematological parameters were not adversely affected by land-treatment; however, platelet counts were 26% greater in cotton rats from land-treatment sites compared to reference sites in winter. Significant treatment-related differences were observed in total serum protein concentrations, organ mass and organ cellularity, but these differences were not consistent across the five land-treatment units. Lymphoproliferative responses of cotton rat splenocytes stimulated in vitro were elevated for a T-cell mitogen and depressed for a B-cell mitogen in animals from land-treatment compared to reference sites. The ability of splenocytes to proliferate in response to interleukin-2 receptor-binding was not influenced by treatment. Total yields of peritoneal cells, yield of peritoneal macrophages, and yield of peritoneal lymphocytes were influenced to varying degrees by land-treatment. Functionally, in vitro metabolic activity of peritoneal macrophages was 114% greater in cotton rats from land-treatment sites compared to reference sites during summer. These results indicate that petrochemical wastes applied to soils on these five land treatment sites had variable immunomodulatory effects in resident cotton rats. Immune alterations for some assays were indicative of enhancement on some land treatment sites while suppressive on other land-treatment sites, which could have been a function of type and concentration of immunotoxicants present on each site and highlights the uniqueness of each land-treatment site. PMID- 11202657 TI - Clonal differences in copper and zinc tolerance of birch in metal-supplemented soils. AB - Metal tolerance of a range of birch clones (Betula pendula and Betula pubescens) originating from metal-contaminated sites in England, Wales, Belgium and Finland were tested in soils supplemented with several concentrations of copper (Cu) or zinc (Zn) (500, 2000, 5000 mg kg-1 dry wt. soil of CuSO(4).5H2O or ZnSO(4).7H2O) for 4 months and with sub-toxic metal supplements (500 mg CuSO4, 2000 mg ZnSO4) for 6 months. When grown at high concentrations of metals, severe toxicity symptoms (growth inhibition, chlorosis, necrosis) and clear evidence for differences in tolerance to this toxicity were found in a subset of the clones. When all clones were grown at a much lower, sub-toxic level of metal, again significant differences could be found between some of the clones. Clones derived from the same population varied greatly in their tolerance. However, the overall pattern of metal specificity varied in agreement with the type of soil contamination at the site of origin. The growth of the clones from Harjavalta Cu/nickel smelter area was 19% better in Cu than in Zn-supplemented soil, on average. The growth of clones from Maatheide Zn smelter are was 19% poorer in Cu- than in Zn-supplemented soil. Sensitive clones accumulated more Cu and Zn to the above-ground parts. Some birch clones were able to survive at about 20-fold higher than typical total background Cu or Zn concentrations, whereas most clones were able to grow without serious toxic symptoms at about 10-fold concentrations. PMID- 11202658 TI - The Royal College and the dying joy of learning. PMID- 11202659 TI - Calculating waiting times retrospectively. PMID- 11202660 TI - Calculating waiting times retrospectively. PMID- 11202661 TI - MDs, maternity leave and adopted children. PMID- 11202662 TI - Effect of domperidone on milk production in mothers of premature newborns: a randomized, double-blind, placebo-controlled trial. AB - BACKGROUND: Varying degrees of success have been reported with strategies to increase milk production when lactation is failing. The objective of this study was to investigate the efficacy of domperidone in augmenting milk production in mothers of premature newborns. METHODS: Twenty patients were randomly assigned to receive either domperidone or placebo for 7 days. Milk volume was measured daily. Domperidone levels were measured in randomly selected milk and serum samples on day 5 of the study. Serum prolactin levels were measured before the start of the study, on day 5 and on day 10 (3 days after the last dose of the study medication). RESULTS: Data from 16 patients were available for analysis (7 in the domperidone group and 9 in the placebo group). When compared with baseline values, the mean increase in the volume of milk production from day 2 to 7 was 49.5 (standard deviation [SD] 29.4) mL in the domperidone group and 8.0 (SD 39.5) mL in the placebo group (p < 0.05); proportionally this represented an increase of 44.5% and 16.6% respectively. The serum prolactin levels were similar in the 2 groups at baseline; by day 5 they were significantly higher in the domperidone group than in the placebo group, returning to baseline levels in both groups 3 days after the last dose of the study medication. Very small amounts of domperidone were detected in the breast milk samples. INTERPRETATION: In the short term domperidone increases milk production in women with low milk supply and is detected at low levels in breast milk. PMID- 11202664 TI - Determinants of violence in the psychiatric emergency service. PMID- 11202663 TI - Undiagnosed diabetes: does it matter? AB - BACKGROUND: The 1998 Canadian clinical practice guidelines for the management of diabetes lowered the cutoff point for diagnosing diabetes mellitus from a fasting plasma glucose (FPG) level of 7.8 to 7.0 mmol/L. We studied the prevalence and clinical outcomes of undiagnosed and diagnosed diabetes within specific ranges of FPG among a cohort of subjects recruited in 1990. METHODS: In 1990 a representative sample of 2792 adult residents of Manitoba participated in the Manitoba Heart Health Survey, which included measurement of FPG and a question about each participant's past history of diabetes. Individuals who would now be classified as having undiagnosed diabetes under the new criteria were not considered as such in 1990. Through data linkage with the provincial health care utilization database, the use of health care by these individuals was tracked and compared with that of individuals whose diabetes had been diagnosed and with that of normoglycemic individuals over an 8-year period subsequent to the survey. RESULTS: The prevalence of undiagnosed diabetes in the adult population of Manitoba was 2.2%. Undiagnosed cases accounted for about one-third of all diabetes cases. Individuals with undiagnosed diabetes had an unfavourable lipid profile and higher blood pressure and obesity indices than normoglycemic individuals. Individuals who satisfied the new criteria for diabetes but remained undiagnosed had an additional 1.35 physician visits per year (95% confidence interval [95% CI] 0.93-1.96) and were more likely to be admitted to hospital at least once (odds ratio 1.23, 95% CI 0.40-3.79), compared with normoglycemic individuals. INTERPRETATION: Undiagnosed cases represent the unseen but clinically important burden of diabetes, with significant concurrent metabolic derangements and a long-term impact on health care use. PMID- 11202665 TI - Mass influenza vaccination in Ontario: a sensible move. PMID- 11202666 TI - Mass influenza vaccination in Ontario: is it worthwhile? PMID- 11202667 TI - Another modest proposal. PMID- 11202668 TI - What goes around, comes around: a history of medical tuition. AB - In this article the actual and relative costs of tuition at 3 Ontario medical schools are traced over the past 150 years. In addition, the factors that led to Ontario's nearly 4-decade experiment in private medical education (and to its eventual demise) are presented. In relative terms, tuition was stable for over a century, then declined (after 1960) as government support rose. Access to medical training for students from middle-income families may also have improved steadily until the late 1980s. Because there is no shortage of people wanting to become doctors, there seems to be no limit to the price that could be set for a medical education. The recent hikes in tuition have outstripped inflation and may be reducing accessibility to restrictive levels, similar to those that prevailed in the 19th century. The author invites readers to question current trends. PMID- 11202669 TI - Bioethics for clinicians: 21. Islamic bioethics. AB - Islamic bioethics derives from a combination of principles, duties and rights, and, to a certain extent, a call to virtue. In Islam, bioethical decision-making is carried out within a framework of values derived from revelation and tradition. It is intimately linked to the broad ethical teachings of the Qur'an and the tradition of the Prophet Muhammed, and thus to the interpretation of Islamic law. In this way, Islam has the flexibility to respond to new biomedical technologies. Islamic bioethics emphasizes prevention and teaches that the patient must be treated with respect and compassion and that the physical, mental and spiritual dimensions of the illness experience be taken into account. Because Islam shares many foundational values with Judaism and Christianity, the informed Canadian physician will find Islamic bioethics quite familiar. Canadian Muslims come from varied backgrounds and have varying degrees of religious observance. Physicians need to recognize this diversity and avoid a stereotypical approach to Muslim patients. PMID- 11202670 TI - Environment and health: 7. Species loss and ecosystem disruption--the implications for human health. PMID- 11202671 TI - Health care got short shrift in an election about nothing. PMID- 11202672 TI - WHO compares tobacco to land-mine threat, seeks international rules. PMID- 11202673 TI - Will Canada follow US lead on RU 486? PMID- 11202674 TI - Going green? Go online. PMID- 11202676 TI - Military's environmental medicine research pushes limits of human endurance. PMID- 11202675 TI - Greening of health care goal of new coalition. PMID- 11202677 TI - HRT and venous thromboembolism: more evidence of a link. PMID- 11202678 TI - Snowboarding injuries: hitting the slopes. PMID- 11202679 TI - Thioridazine (Mellaril) and mesoridazine (Serentil): prolongation of the QTc interval. PMID- 11202680 TI - Clopidogrel (Plavix): hematological reactions. PMID- 11202681 TI - Gentamicin ear drops and ototoxicity: update. PMID- 11202682 TI - Whither marine radioactivity studies? PMID- 11202683 TI - Effect of chemical pollution on forms of 137Cs, 90Sr and 239,240Pu in arctic soil studied by sequential extraction. AB - The aim of the present study was to determine the forms of 137Cs, 90Sr and 239,240Pu occurring in different soil horizons using sequential extraction of samples taken from four sites located along a pollution gradient from the copper nickel smelter at Monchegorsk in the Kola Peninsula, Russia, and from a reference site in Finnish Lapland in 1997. A selective sequential-leaching procedure was employed using a modification of the method of Tessier, Cambell and Bisson ((1979). Analytical Chemistry, 51, 844-851). For 137Cs the organic (O) and uppermost mineral (E1) layer were studied, for 90Sr and 239,240Pu only the uppermost organic layer (Of). The fraction of 137Cs occurring in readily exchangeable form in the organic layer was about 50% at the reference site and decreased as a function of pollution, being 15% at the most polluted site in the Kola Peninsula. There was a clear positive correlation in the O layer between the distance from the smelter and the percentage of 137Cs extracted in the readily exchangeable fraction (Spearman correlation rsp = 0.7805, p = 0.0001), whereas in the E1 layer no correlation was evident. The distribution of 90Sr in the Of layer was similar at all sites, with the highest amounts occurring in exchangeable form and bound to organic matter, whereas stable Sr showed a somewhat different distribution with the highest amount in the oxide fraction. Most of the 239,240Pu was bound to organic matter. Chemical pollution affected the exchangeable fraction of 239,240Pu, which was about 1% at the most polluted site and 4-6% at the other sites. PMID- 11202684 TI - Predicting the transfer of radiocaesium from organic soils to plants using soil characteristics. AB - A model predicting plant uptake of radiocaesium based on soil characteristics is described. Three soil parameters required to determine radiocaesium bioavailability in soils are estimated in the model: the labile caesium distribution coefficient (kd1), K+ concentration in the soil solution [mK] and the soil solution-->plant radiocaesium concentration factor (CF, Bq kg-1 plant/Bq dm-3). These were determined as functions of soil clay content, exchangeable K+ status, pH, NH4+ concentration and organic matter content. The effect of time on radiocaesium fixation was described using a previously published double exponential equation, modified for the effect of soil organic matter as a non fixing adsorbent. The model was parameterised using radiocaesium uptake data from two pot trials conducted separately using ryegrass (Lolium perenne) on mineral soils and bent grass (Agrostis capillaris) on organic soils. This resulted in a significant fit to the observed transfer factor (TF, Bq kg-1 plant/Bq kg-1 whole soil) (P < 0.001, n = 58) and soil solution K+ concentration (mK, mol dm-3) (P < 0.001, n = 58). Without further parameterisation the model was tested against independent radiocaesium uptake data for barley (n = 71) using a database of published and unpublished information covering contamination time periods of 1.2 10 years (transfer factors ranged from 0.001 to 0.1). The model accounted for 52% (n = 71, P < 0.001) of the observed variation in log transfer factor. PMID- 11202685 TI - Long-term studies on transfer of 137Cs from soil to vegetation and to grazing lambs in a mountain area in northern Sweden. AB - Studies were made during 1990-1997 on the transfer of 137Cs from soil to vegetation (herbage) and to grazing lambs on a mountain farm with an uncultivated grazing area of about 10 km2. The farm is situated in an area in Northern Sweden which was contaminated by the Chernobyl fallout in 1986. The mean concentration of 137Cs in the soil to a depth of 10 cm for eight sampling sites observed in the 8-year period was 14.51 kBq/m2, while in the cut herbage the average concentration was 859 Bq/kg d.w. and in lamb meat 682 Bq/kg w.w. A slow vertical migration of 137Cs in the 0-10 cm soil layer was indicated. Although the 137Cs concentration in herbage gradually decreased, the concentration in lamb meat varied from year to year. Soil ingestion by the lambs as a pathway for activity transfer was shown to be negligible, while ingestion of fungi with high concentrations of 137Cs was demonstrated to occur, as large numbers of fungi spores were counted in samples of the lambs' faeces. Fungi ingestion might therefore partly explain the varying mean yearly 137Cs concentrations in lamb muscle. The mean transfer parameters were as follows: for "soil to herbage" 61.3 Bq/kg d.w. herbage per kBq/m2 soil, for "herbage to lamb meat" 0.81 Bq/kg w.w. meat per Bq/kg d.w. herbage, and for "soil to lamb meat" 47.1 Bq/kg w.w. meat per kBq/m2 soil. A trend of decreasing values of the transfer parameter for "soil to herbage" indicated that 137Cs was becoming less available for root-uptake with time. The effective ecological half-life of 137Cs in soil, herbage and lamb meat was calculated to be 19, 7 and 16 years, respectively. It can be concluded that natural areas are vulnerable to 137Cs contamination, resulting in high concentrations in plants, fungi and lamb meat for a long time. PMID- 11202686 TI - Resuspension of coarse fuel hot particles in the Chernobyl area. AB - Measurements of resuspended aerosol in the Chernobyl 30-km exclusion zone have shown coarse fuel hot particles in the activity range 1-12 Bq 137Cs per particle. The particles were sampled with newly designed rotating arm impactors which simultaneously collect during the same experiment three samples with fuel particles in the size ranges larger than 3 microns, larger than 6 microns and larger than 9 microns in geometric diameter. The radionuclide ratios, determined after gamma-spectrometry, were in good agreement with the theoretical calculations for the radionuclide-composition of the Chernobyl Nuclear Power Plant at the moment of the accident and the measured hot particles in soil in the early years after the accident. The number concentrations of airborne hot particles were derived from digital autoradiography. For wind resuspension, maximal concentrations of 2.6 coarse hot particles per 1000 m3 and during agricultural activities 36 coarse hot particles per 1000 m3 were measured. The geometric diameter of single hot particles was estimated to be between 6 and 12 microns. PMID- 11202687 TI - Physical resuspension and vertical mixing of sediments on a high energy continental margin (Sydney, Australia). AB - Four sediment cores from the continental margin adjacent to Sydney were analyzed for 210Pb, 137Cs, trace metals (Ag, Cd, Co, Cu, Mn, Ni, Pb, Zn), iron, dry bulk density, mud and moisture content. The concentrations of trace metals in the total sediment are low at all sites, although slightly elevated concentrations of Ag, Cu, Pb and Zn are present in the fine fraction of sediment (< 62.5 microns) near a major ocean outfall. Concentrations of trace metals in the fine fraction of sediment are similar in the upper 10-15 cm, indicating strong vertical mixing of the sediments, whereas an upward coarsening grain size in the upper 1-3 cm of sediment supports physical resuspension during storms. Sediment accumulation rates on the middle shelf adjacent to Sydney were estimated from downcore profiles of 210Pb and 137Cs and range between 0.2 and 0.4 cm yr-1. Although the mass fluxes of Cu, Pb and Zn within a distance of 2 km from the outfall (up to 36.1, 30.8 and 86.2 micrograms cm-2 yr-1, respectively) are greater than 20 km north of the outfall (< 23.5 micrograms cm-2 yr-1), the low concentrations of trace metals in sediments near the outfall support an efficient dispersal of anthropogenic contaminants on this continental margin. PMID- 11202688 TI - Radioactive discharges from an alkaline pulp mill located in the south of Spain. AB - Artificial and natural radionuclides present in environmental samples (Eucalyptus wood and bark) can be transferred in an alkaline pulp mill and concentrated in the recycling process. Some part of the radionuclides can be released into the environment associated with the discharges from such a factory. An alkaline pulp mill located in the South of Spain was extensively sampled during 1993 and different radionuclides analysed in the collected samples. Thus the concentrations and fluxes of natural (40K, 226Ra, 228Ra and 228Th) and artificial (137Cs and 90Sr) radionuclides associated with the samples collected along the pulp production process are presented. It is shown that radium and thorium radionuclides behave similarly to strontium and calcium and, consequently, concentrate within the Ca-cycle. Furthermore, 40K and 137Cs are concentrated during the Na-cycle. Finally, the results obtained by the authors are compared with the levels found in similar factories, though situated in the North of Europe, by other researchers. PMID- 11202690 TI - The Swedish nuclear dilemma. PMID- 11202689 TI - Radionuclides in hot mineral spring waters in Jordan. AB - Hot mineral springs in Jordan are very attractive to people who seek physical healing but they are unaware of natural radioactive elements that may be contained in the hot mineral water. The activities of the natural radioactive isotopes were measured and the concentrations of the parents of their natural radioactive series were calculated. The measured radionuclides were 234Th, 226Ra, 214Pb, 214Bi, 228Ac, 228Th, 212Pb, 212Bi and 208Tl. In addition the activities of 235U and 40K were measured. The activities ranged from 0.14 to 34.8 Bq/l, while the concentrations of parent uranium and thorium isotopes ranged from 3.0 x 10( 3) to 0.59 mg/l. The results were compared with those for drinking water. PMID- 11202691 TI - Radionuclide transfer to fruits: A critical review. Foreword. AB - After completion of the (Validation of Environmental Model Predictions) (VAMP) and (BIOspheric Model Validation Study) (BIOMOVS II) Programmes, the Division of Radiation and Waste Safety of the IAEA decided to promote a new co-ordinated research programme to continue activities in the area of biosphere modelling. As a result, the BIOMASS Programme on BIOsphere Modelling and ASSessment was launched in Vienna in October 1996. The Programme is scheduled to finish in October 2000. The overall objective of BIOMASS is to provide an international focal point in the area of biosphere assessment modelling. There are 3 Themes and 11 working groups in BIOMASS. The objective of the Theme 3 Fruits Working Group is to improve understanding of the uptake and transfer of radionuclides from different sources to fruit. As part of the work programme, a review was undertaken of the experimental, field and modelling information on the transfer of radionuclides to fruit. PMID- 11202692 TI - Radionuclide transfer to fruits: a critical review. Introduction. AB - This paper provides a brief introduction to fruit, their definition, classification and geographical distribution. In the following review, the term "fruit" refers not to a well-defined botanical plant part but, in the horticultural sense, to a component of the human diet generally consumed as a dessert item. Plants that bear fruits cover a vast range of morphological and physiological traits. A generic classification of fruit-bearing plants is proposed for use in studies on radionuclide transfer to fruit. PMID- 11202693 TI - The influence of the development of temperate fruit tree species on the potential for their uptake of radionuclides. AB - This paper reviews the published literature that describes the phenological development of above and below ground organs of temperate fruit trees (top fruit), particularly with respect to apple (Malus domestica). Critical information is presented which is considered appropriate in developing an understanding of the potential for top fruit species to take up radionuclide contaminants from the atmosphere and the soil. Information is cited on how climatic and edaphic factors influence the growth and development of temperate fruit trees, the phenological production of their leaf area and the development and growth of their fruit and hence the potential for foliar and fruit uptake of radionuclides from the atmosphere. The study also reports on the importance of the distribution and phenological development of roots in the soil and the potential for their uptake of radionuclides from the soil. The effects of above and below ground management procedures, within temperate fruit orchards, on potential radionuclide uptake are also considered. It is concluded that the potential for the uptake of radionuclides by temperate fruit tree species will depend on a number of phenological and physiological factors. For uptake from the soil these factors include; root distribution and density in the soil profile, seasonal changes in the production and distribution of roots, and the presence and amount of water in the soil. These factors are themselves influenced by rootstock type and its growth vigour, scion type and its growth vigour, tree age, spacing of trees in the orchard, orchard management practices (presence or absence of weeds or grass under the trees) and soil type and depth. Direct uptake by the shoot, however, will be influenced by the climatic conditions at the time of exposure and the presence of foliage. Deposition and uptake are likely to change with leaf area development and the ability of radionuclides to penetrate the cuticle of the leaf changes with seasonal development. Transport of radionuclides to the fruit may also depend on the time of season, as the importance of the xylem and phloem transport routes can change with the growth and development of the fruit. PMID- 11202694 TI - The role of fruit in the diet. AB - Data on the production and consumption of fruit are reviewed in the context of modelling the transfer of radionuclides to fruit, and the assessment of the consequent risks to the consumers. Mean consumption rates vary widely from country to country, from 150 g per day fresh weight to about 500 g per day. Consumption also varies with age, socio-economic class, and climate. In some countries there is a trend towards increased consumption of fruit, associated with a growing interest in a healthy diet, and these trends have been associated with changes in the incidence of cardio-vascular diseases and some forms of cancer. Assessment of the effects of radionuclides in fruit needs to take into account the use of wild growing fruits, the increasing trade in fruit between countries, and the contribution from natural radionuclides in fruit. PMID- 11202695 TI - Transfer of radioactivity to fruit: significant radionuclides and speciation. AB - One of the roles of the BIOMASS Theme 3 Fruit Working Group was to identify significant radionuclides to support its work programme. This paper provides a short review of radionuclide emissions to atmosphere together with comments on their relative dosimetric impacts to identify those radionuclides most relevant to the Fruit Working Group. Speciation of the identified radionuclides is also discussed to identify the most likely chemical forms to which fruits might be exposed. It is noted that no information currently exists on radionuclide speciation in regard to the uptake and retention of radionuclides in fruit crops. PMID- 11202696 TI - Deposition of gaseous radionuclides to fruit. AB - 14C, 35S and 3H are released to the environment during the operation of gas cooled reactors and were identified as radionuclides of interest by the BIOMASS Fruits Working Group. This paper provides a review of the deposition, uptake, allocation and loss of these radionuclides with respect to fruit and conceptual models for gaseous radionuclides. It is concluded that the mechanisms for the uptake of CO35S, HTO and 14CO2 are well understood and that their deposition velocities have been quantified. There is also a reasonable body of work on the translocation of 14C once in the crop, but much less for 35S and 3H, which are considered to follow source-sink relationships. The loss rates of the three radionuclides show large differences, with tritium lost rapidly in the form of HTO but retained longer when converted to OBT. The losses of 14C are less and those of sulphur are minimal post fixation. When fruit crops alone are considered, the quantity of information is further reduced but predictions on possible behaviour of these radionuclide species can be made from the current knowledge. PMID- 11202697 TI - Aerial contamination of fruit through wet deposition and particulate dry deposition. AB - The current state of knowledge concerning the processes and pathways which lead to the contamination of fruit crops by non-gaseous airborne contaminants is reviewed. Given the wide range of fruit canopies which occur, it is necessary to look for generic factors which affect the contribution of each of these processes and pathways to distribution through the canopy, losses from the canopy back to the atmosphere, and the fate of particle-bound substances once attached to the canopy. This latter stage represents perhaps the greatest source of uncertainty in determining levels of contamination. For wet deposition, the controlling factors appear to be the ability of the canopy surface to store precipitated water, and the interaction of the contaminant species with the leaf cuticle, which appears to act as an ion exchange medium, selectively accumulating certain ionic species. Where possible, models and parameterisations are provided for these stages. A summary is given of current data requirements for those cases where this is not possible. PMID- 11202698 TI - Post-deposition transport of radionuclides in fruit. AB - This paper considers two main pathways for contamination of fruit by radionuclides: (i) absorption after deposition directly to exposed fruit surfaces, and (ii) absorption after deposition to other exposed plant surfaces followed by translocation to fruit. The aim is to collect the available information on fruit from temperate regions, identify the factors affecting post deposition processes in fruit plant systems, identify gaps in knowledge and give recommendations for future work. The majority of information available on above ground absorption and further translocation to fruit concerns 134Cs and 85Sr in soluble form in apple, strawberry and grapevine. In general, 85Sr is absorbed and translocated to a lesser extent than is 134Cs. The rate of absorption and translocation depends on the physiological stage and age of the plant, and varies between different plant species and varieties. PMID- 11202699 TI - Radionuclide transfer from soil to fruit. AB - The available literature on the transfer of radionuclides from soil to fruit has been reviewed with the aim of identifying the main variables and processes affecting the behaviour of radionuclides in fruit plants. Where available, data for transfer of radionuclides from soil to other components of fruit plant have also been collected, to help in understanding the processes of translocation and storage in perennial plants. Soil-to-fruit transfer factors were derived from agricultural ecosystems, both from temperate and subtropical or tropical zones. Aggregated transfer factors have also been collected from natural or semi-natural ecosystems. The data concern numerous fruits and various radionuclides. Soil-to fruit transfer is nuclide specific. The variability for a given radionuclide is first of all ascribable to the different properties of soils. Fruit plant species are very heterogeneous, varying from woody trees and shrubs to herbaceous plants. In temperate areas the soil-to-fruit transfer is higher in woody trees for caesium and in shrubs for strontium. Significant differences between the values obtained in temperate and subtropical and tropical regions do not necessarily imply that they are ascribable to climate. Transfer factors for caesium are higher in subtropical and tropical fruits, while those for strontium, as well as for plutonium and americium, in the same fruits, are lower; these results can be interpreted taking into account different soil characteristics. PMID- 11202700 TI - The effect of storage and processing on radionuclide content of fruit. AB - After harvesting, the activity content of fruits may still be affected by the manner in which they are treated. Long storage times will reduce the activity contents of short-lived radionuclides; preparation and/or processing may cause activity to be physically removed. This paper presents the results of a review of the available literature on these effects. Data are scarce for both storage and processing, the majority of information on the latter being for 137Cs and 90Sr. For cautious general assessments, it should be assumed that there is no delay and that no activity is lost on processing, especially if the fruits can be eaten raw. However, individual cases may require specific data if available. The use of storage of processing as specific counter-measures to reduce activity concentrations in fruits may not be acceptable to the consumer, especially where alternative, non-contaminated, foodstuffs are readily available. PMID- 11202701 TI - Models for radionuclide transfer to fruits and data requirements. AB - This paper presents a review of available models for radionuclide transfer to fruit with particular emphasis on the model types and the purpose for which they were developed. It is clear that the model structures that have been developed range from the simple to the complex and that the underlying data on which they are based is incomplete. The work programme of the BIOMASS Theme 3 Fruits Working Group includes model inter-comparison and model validation studies that will give an indication of the performance of the different model types discussed here. The models included in these comparative studies include several new and as yet unpublished models. In the case of fruit, there is an urgent need for data on changing radionuclide distribution in plant organs with time to increase confidence in current models. PMID- 11202702 TI - Reproductive impairment of sea urchins upon chronic exposure to cadmium. Part I: Effects on gamete quality. AB - Successful reproduction is a determining factor for species survival. Pollution may impair reproductive success of adults through effects on gamete quality. Reproductive impairment of the sea urchin Anthocidaris crassispina upon chronic (4 weeks) exposure to 0.01 and 0.1 mg l-1 Cd2+ was investigated. Criteria used for assessing gamete quality included sperm motility, egg morphology, fertilization rate and dynamics of first cleavage. A dose-response relationship was found between Cd2+ levels and changes in sperm motility, and percentage fertilization. Sperm motility, measured by computer-assisted sperm analysis, indicated that percent motile sperm, velocities, and percent sperm with normal trajectory were significantly affected by chronic exposure to > or = 0.1 mg l-1 Cd2+. A decline in sperm motility was also accompanied by a decrease in fertilization success of sea urchin sperm. Width/height ratio of sea urchin eggs was not affected by cadmium, but larger egg sizes were found when sea urchins were exposed to 0.1 mg l-1 Cd2+. Male sea urchins exposed to Cd2+ produced poorer quality sperm, as indicated by a lower percent fertilization and lower cleavage rate, implying that male sea urchins were more sensitive than females to chronic Cd2+ exposure. Results of the present study provide an explanation of reproductive impairment in marine invertebrates upon chronic exposure to Cd2+. PMID- 11202703 TI - Mercury in feathers of Squacco Heron (Ardeola ralloides) chicks in relation to age, hatching order, growth, and sampling dates. AB - We studied the relationships between mercury content of Squacco Heron (Ardeola ralloides) chick body-feathers and nestling age, hatching order (seniors-juniors) and growth parameters, and the date of feather sampling in the Axios Delta, northern Greece, in 1993 (n = 75 chicks) and 1994 (n = 80). Mercury levels were not significantly correlated with chick age in either year of the study. Most of the variability in mercury (90%) was found among broods, attributable to differential prey selection and/or foraging habitat and patch utilization by parents. Within broods, juniors had significantly higher mercury loads than seniors in 1993, but there was no significant difference between the two in 1994. Correlations of nestling weight and linear measurements corrected for chick age and mercury concentrations were never significant and explained small amounts of variability in chick growth. However, linear measurements corrected for age were significantly higher among seniors in 1993, when those nestlings had lower mercury loads than their siblings. Mercury levels were unaffected by the date of feather collection in 1993, but exhibited a significant increase over time in 1994. This can be attributed to a shift towards more highly contaminated habitats and prey types by foraging parents, resulting from seasonal changes in water level and vegetation cover in important foraging habitats. Feather collection from Squacco Heron nestlings late in the breeding season seems to be an appropriate method for biomonitoring mercury pollution in the Axios Delta. PMID- 11202704 TI - Reproductive impairment of sea urchin upon chronic exposure to cadmium. Part II: Effects on sperm development. AB - Chronic pollution may impair the reproductive success of adult organisms through a decrease in the quality of gametes. Our parallel study on gamete quality, showed that male sea urchins were more sensitive than the females towards cadmium pollution. The effects of chronic exposure to 0.01 and 1 ppm Cd2+ on sperm development of the sea urchin Anthocidaris crassispina were studied. Despite the fact that no significant change in gonad index was observed when sea urchins were exposed to both levels of Cd2+ for 4 weeks, deposition of electron-dense materials was conspicuous at the wall and intracellular space of male gonads. Apparent cytological alterations were observed in sperm cells, including changes in morphology of nuage in spermatogonia. The discrete, granular bodies of nuage were replaced by a large electron-dense body. Spermatozoa with short, incomplete 'broken' tails (scanning electron microscope observation) or tails of spermatids/spermatozoa with extraordinary electron-density (transmission electron microscope observation) were more abundant in gonads exposed to both levels of Cd2+. Mitochondrial cristae deformation was observed for sperm cells at all stages of development. Sperm plasma membrane also became more convoluted but acrosome remained intact. The observed cytological distortion of sperm tails and mitochondria/midpiece could help to explain the decline in motility as well as poor perseverance in sperm produced by sea urchins exposed to cadmium observed in our earlier study. PMID- 11202705 TI - Trace metals in seagrass, algae and molluscs from an uncontaminated area in the Mediterranean. AB - The concentrations of Cd, Cr, Cu, Pb and Zn were measured in specimens of four marine organisms--the seagrass Posidonia oceanica (L.) Delile, the brown algae Padina pavonica (L.) Thivy, and the two gastropod molluscs Monodonta turbinata Born and Patella caerulea L.--selected as possible cosmopolitan biomonitors of trace metals in the Mediterranean area. The organisms were collected at five coastal sites in Favignana Island (Sicily, Italy), an area virtually uninfluenced by anthropogenic activities. In order to gain a more complete picture of both the environmental conditions of the experimental area and the bioaccumulation patterns of the selected organisms, soluble and total metal concentrations were determined in coastal water samples collected at the same stations. The picture of bioavailable metal loads in the different sites of the selected area provided by the four species was rather univocal. An overall trend of increased metal concentrations at the station in which the local harbour is located was clear. On the other hand, the metal concentrations recorded at the 'clean' stations generally fall in the range of the lowest values available in the literature and may be considered as useful background levels to which to refer for intraspecific comparison within the Mediterranean area. Implications in biomonitoring of the observed accumulation patterns, especially in the different tissues of Posidonia oceanica, are discussed. PMID- 11202706 TI - Photosynthesis and biomass allocation of radish cv. "Cherry Belle" in response to root temperature and ozone. AB - To determine if ozone (O3) and root zone temperature (RZT) affect plant biomass allocation and photosynthesis, radish (Raphanus sativus) plants were grown in controlled environment laboratory chambers in one of four treatments: episodic O3 (average delivery 0.063 mumol mol-1) with RZT at 13 degrees C, episodic O3 (same delivery) with RZT at 18 degrees C, charcoal-filtered air with RZT at 13 degrees C and charcoal-filtered air with RZT at 18 degrees C. O3 reduced total biomass and shoot biomass of radish at 13 degrees C RZT but had no effect at 18 degrees C RZT. Low (13 degrees C) RZT decreased total biomass in both O3 and charcoal filtered air. RZT had no overall effect on biomass allocation, but O3 lowered root-to-shoot ratios for plants grown at 18 degrees C RZT. Photosynthesis was reduced for plants grown at 18 degrees C RZT and O3, but stomatal conductance was not affected by O3 nor RZT. These results indicate that O3 and low RZT decrease biomass, but that plant photosynthesis is decreased by O3 and warm RZT. PMID- 11202707 TI - Lead shot toxicity to passerines. AB - This study evaluated the toxicity of a single size 7.5 lead shot to passerines. No mortalities or signs of plumbism were observed in dosed cowbirds (Molothrus ater) fed a commercial diet, but when given a more natural diet, three of 10 dosed birds died within 1 day. For all survivors from which shot were recovered, all but one excreted the shot within 24 h of dosing, whereas, the dead birds retained their shot. Shot erosion was significantly greater (P < 0.05) when weathered shot were ingested compared to new shot, and the greatest erosion was observed in those birds that died (2.2-9.7%). Blood lead concentrations of birds dosed with new shot were not significantly different (P = 0.14) from those of birds exposed to weathered shot. Liver lead concentrations of birds that died ranged from 71 to 137 ppm, dry weight. Despite the short amount of time the shot was retained, songbirds may absorb sufficient lead to compromise their survival. PMID- 11202708 TI - Effects of environmental and maternally derived methylmercury on the embryonic and larval stages of walleye (Stizostedion vitreum). AB - The effects of environmental and maternally derived methylmercury (MeHg) on the embryonic and larval stages of walleye (Stizostedion vitreum) were investigated using eggs collected during two successive spawning seasons. Eggs were collected from fish in a mercury (Hg)-polluted environment (Clay Lake, Ontario, Canada), and from fish in two relatively pristine lakes (Lakes Manitoba and Winnipeg, in the province of Manitoba). Both bioaccumulation of Hg into muscle and its mobilization into eggs was significantly higher in Clay Lake females. Maternal muscle MeHg concentration was positively correlated with female length and egg MeHg was positively correlated with muscle MeHg concentration in all three populations. Hatching success of eggs from all three stocks declined significantly with increasing waterborne MeHg (0.1-7.8 ng l-1). Hatching success was not significantly affected by egg MeHg concentration. Embryonic heart rate declined with increasing waterborne MeHg concentration, but larval growth was not affected. Occurrence of larval deformities was negatively correlated with size of female, but was not significantly correlated with MeHg in either eggs or water. Larval MeHg was positively correlated with the concentrations of MeHg in eggs demonstrating transmission of MeHg from females. Uptake of ambient MeHg was higher in larvae exposed to higher waterborne MeHg concentrations. PMID- 11202709 TI - Sources, distribution and variability of airborne trace metals in La Plata City area, Argentina. AB - Airborne particulate trace metals have been measured bimonthly during day and night hours in four permanent stations located in residential, industrial and commercial sectors of La Plata City region, to characterize the sources and variability of atmospheric inputs. Airborne trace metal regional averages (Pb 64 +/- 62, Cu 30 +/- 27, Mn 26 +/- 20, Zn 273 +/- 227, Fe 1183 +/- 838, Ca 5343 +/- 3614, Mg 1472 +/- 967, Cr 4.3 +/- 2.4, Ni 3.2 +/- 3.5 and Cd 0.41 +/- 0.42 ng/m3) are comparable to the values reported for not grossly polluted cities and below the general trend described for urban particulates. Two- and three-way analysis of variance and variance components tests (P < 0.05) were performed to assess the contribution of the diurnal (day vs. night), spatial (inter-station) and temporal (inter-month) components of variability. Trace metal concentrations followed the behavior of total suspended particles with higher concentrations during the day and at the Downtown station and lower at the Residential site. In general, spatial and temporal variations prevailed over diurnal differences. Spatial differences were clearly most significant for Pb, which presented higher values at the Downtown site reflecting the importance of motor exhaust inputs. In contrast, diurnal differences were more important for Mn due to increased dust resuspension during day hours. A seasonal trend with concentrations usually increasing during winter months and decreasing in spring-summer was also detected. Enrichment factors (EF) were calculated to evaluate anthropogenic versus natural element sources. High EF (21-376) were obtained for Pb, Zn, Cd and Cu reflecting the importance of anthropic inputs. The comparison with EF calculated for high-emitting vehicle particle emissions indicated that motor exhausts are the most important source of these elements in La Plata region. In contrast, the EF calculated for Mn, Cr, Ni, Ca and Mg were low (1.3-7.5) suggesting chiefly natural sources, i.e. soil-derived dusts. PMID- 11202710 TI - The relationship between trace metal contamination and stream meiofauna. AB - The effect of chemical contaminants on freshwater meiofaunal communities is poorly understood and meiofauna rarely form part of environmental impact assessments in fresh waters. The community composition and diversity of meiofauna in streams of southwest England (Cornwall) representing a gradient in trace metal contamination were investigated. Multivariate and univariate statistical techniques were used to correlate community composition, diversity and environmental variables. Meiofaunal communities were very different at sites with high compared with low metal concentrations. Copper, either singly, or in combination with other environmental variables (aluminium, zinc or dissolved organic carbon), was the most important correlate with community composition. Not all meiofaunal species were adversely affected by metals, however, and some taxa, most notably certain cyclopoid copepods, were abundant at high metal concentrations. Moreover, sites with high metal concentrations were not significantly less diverse than sites of low metal concentrations. These data suggest that metal contamination significantly alters the composition of stream meiofaunal assemblages and highlight the importance of including meiofauna in impact studies of fresh waters. PMID- 11202711 TI - Fate and effect of monoalkyl quaternary ammonium surfactants in the aquatic environment. AB - The effect of the alkyl chain of quaternary ammonium-based surfactants on their aquatic toxicity and aerobic biodegradability has been studied. Two families of monoalkylquats surfactants were selected: alkyl trimethyl ammonium and alkyl benzyl dimethyl ammonium halides. Acute toxicity tests on Daphnia magna and Photobacterium phosphoreum were carried out and EC50 values in the range of 0.1-1 mg/l were obtained for the two series of cationic surfactants. Although the substitution of a benzyl group for a methyl group increases the toxicity, an incremental difference in toxicity between homologs of different chain length were not observed. Biodegradability of the different homologs was determined not only in standard conditions but also in coastal water, both tests yielding similar results. An increase in the alkyl chain length or the substitution of a benzyl group for a methyl group reduces the biodegradation rate. The degradation of these compounds in coastal waters was associated with an increase in bacterioplankton density, suggesting that the degradation takes place because the compound is used as a growth substrate. PMID- 11202712 TI - Rapid reductive dechlorination of atrazine by zero-valent iron under acidic conditions. AB - The dechlorination of atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5 triazine) via reaction with metallic iron under low-oxygen conditions was studied using reaction mixture pH values of 2.0, 3.0, and 3.8. The pH control was achieved through addition of sulfuric acid throughout the duration of the reaction. The lower the pH of the reaction mixture, the faster the degradation of atrazine. The surface area of the sulfuric acid-treated iron particles was 0.31 (+/- 0.01) m2 g-1 and the surface area normalized initial pseudo-first order rate constants (kSA, where rate = kSA x (surface area/l) x [Atrazine]) at pH values of 2.0, 3.0, and 3.8 were equal to, respectively, 3.0 (+/- 0.4) x 10(-3) min-1 m-2 l, 5 (+/- 3) x 10(-4) min-1 m-2 l, and 1 (+/- 1) x 10(-4) min-1 m-2 l. The observed products of the degradation reaction were dechlorinated atrazine (2 ethylamino-4-isopropylamino-1,3,5-triazine) and possibly hydroxyatrazine (2 ethylamino-4-isopropylamino-6-hydroxy-s-triazine). Triazine ring protonation may account, at least in part, for the observed effect of pH on atrazine dechlorination via metallic iron. PMID- 11202713 TI - Tris (4-chlorophenyl) methane and tris (4-chlorophenyl) methanol in marine mammals from the Estuary and Gulf of St. Lawrence. AB - Levels of tris (4-chlorophenyl) methanol (TCPM) and its presumed precursor tris (4-chlorophenyl) methane (TCPMe) are reported in marine mammals from the Estuary and Gulf of St. Lawrence, Canada. These compounds were measured in blubber samples of seals and whales using ion trap mass spectrometry (MS/MS) detection. Detectable concentrations of both TCPM and TCPMe were observed in all of the samples analysed. Concentrations of these compounds varied with species ranging from 1.7 to 153 and from 1.3 to 50.6 ng/g lipid wt. for TCPM and TCPMe, respectively. TCPM was from 1.3 to 10 times more concentrated than TCPMe. The highest levels of both TCPM and TCPMe were observed in adult male beluga whales (Delphinapterus leucas) from the St. Lawrence Estuary, while adult female beluga whales from the same area showed levels similar to those in the seals examined. Among the four seal species investigated, TCPM and TCPMe levels were the highest in grey (Halichoerus grypus) and hooded (Cystophora cristata) seals, and lowest in harp seals (Phoca groenlandica). Intermediate levels were found in harbour seals (Phoca vitulina); however, their concentrations might be underestimated considering the younger mean age of these animals. Ratios of both 4,4'-DDE/sigma DDT and TCPM/sigma TCP were very similar between animals from the same species. Strong correlations between sigma TCP and sigma DDT were also observed for each species of mammals, most likely indicating that both sigma TCP and sigma DDT are bioaccumulated in marine mammals. The relationships between sigma DDT and sigma TCP also demonstrate that sigma TCP are less bioaccumulated than sigma DDT by the marine mammal species examined. PMID- 11202714 TI - Comparison among air pollutants, meteorological conditions and some chemical parameters in the transplanted lichen Usnea amblyoclada. AB - The response of Usnea amblyoclada (Mull. Arg.) Zahlbr. to real concentrations of atmospheric pollutants measured by two automatic monitoring stations, was studied in Cordoba City, Argentina. The influence of different weather conditions on the biomonitor's response was also assessed. The concentration of chlorophyll a, chlorophyll b, hydroperoxy-conjugated dienes, and malondialdehyde were quantified in lichen thalli collected from a clean area and in transplanted thalli after 1 month of exposure in an urban area, from April to October, 1996. The dry weight/fresh weight, chlorophyll b/chlorophyll a and phaeophytin a/chlorophyll a ratios were also calculated. Data sets were evaluated by two-way analysis of variance and correlation analysis. It was observed that hydroperoxy-conjugated dienes, malondialdehyde, chlorophylls, and pigment degradation increase during winter-time, when higher levels of suspended particles, non-methane hydrocarbons, hydrogen sulfide and ozone were also measured. These findings would be connected mainly with meteorological conditions, as most pollutants did not exceed prescribed threshold levels. PMID- 11202715 TI - Leaching of chromated copper arsenate wood preservatives: a review. AB - Recent studies have generated conflicting data regarding the bioaccumulation and toxicity of leachates from preservative-treated wood. Due to the scale of the wood preserving industry, timber treated with the most common preservative, chromated copper arsenate (CCA), may form a significant source of metals in the aquatic environment. The existing literature on leaching of CCA is reviewed, and the numerous factors affecting leaching rates, including pH, salinity, treatment and leaching test protocols are discussed. It is concluded from the literature that insufficient data exists regarding these effects to allow accurate quantification of leaching rates, and also highlights the need for standardised leaching protocols. PMID- 11202716 TI - Arsenic and mercury concentrations in major landscape components of an intensively cultivated watershed. AB - To provide an understanding of arsenic (As) and mercury (Hg) concentrations in soil, sediment, water, and fish tissues, samples were collected from a Mississippi River alluvial floodplain located in northwest Mississippi. As concentrations increased approximately an order of magnitude from water (5.12 micrograms/l) to fish tissues (36.99 micrograms/kg) and an additional two orders of magnitude in soils, lake sediments, and wetland sediments (5728, 5614, and 6746 micrograms/kg), respectively. Average Hg concentrations in water, soils, lake sediments, and fish were 2.16 micrograms/l, 55.1, 14.5 and 125 micrograms/kg, respectively. As and Hg concentrations were within published ranges for uncontaminated soil, water, and sediments. As concentrations represented a low risk. Hg concentrations were also low but showed a greater tendency to concentrate in fish tissue. The dominant mode of entry of these materials into aquatic systems is through storm-generated runoff. Since both metals accompany sediments, agricultural conservation practices such as reduced tillage, buffer riparian strips, and bordering sediment ponds or drainage wetlands will minimize watershed input to aquatic systems. PMID- 11202717 TI - Catalytic effect of soil colloids on the reaction between CrVI and p methoxyphenol. AB - Adsorption of CrVI and p-methoxyphenol (PMP) on soil colloids at different pH media was studied. The resulting k1 and n of 1.89 x 10(2) and 0.53 (r2 = 0.99) and k2 and b of 0.13 and 1.25 x 10(3) (r2 = 0.96) were obtained from Freundlich (Q = k1Caqn) and Langmuir [Q = k2bCaq/(1 + k2Caq)] simulation equations, respectively, for CrVI adsorption on soil colloids (pH 4.20). The adsorption of PMP on soil colloids in pH 5.72 media was simulated by five different equations and the results indicated that the Fritz-Schluender one (r2 = 1.00) was the most suitable among them. Adsorption quantity of CrVI and PMP on colloids increased with increasing acidity in the pH range of 3.5-9.0. Study of CrVI adsorption kinetics indicated that the adsorption equilibrium of CrVI was reached rapidly within 2 h. In pure aqueous solution, CrVI reduction by PMP was observed only when the media's pH was lower than 4.0. Oxidation and reduction reaction between CrVI and p-methoxyphenol obviously occurred when soil colloids were involved in this system, even at pH > or = 7.0, which strongly suggested that minerals in soil colloids acted as catalysts to speed the reaction of CrVI and PMP. The oxidized product of PMP by CrVI, extracted by chloroform in acid media and analyzed by gas chromatography-mass spectrometry, was identified as benzoquinone. The reaction included two steps of one electron process. PMID- 11202718 TI - Toxicity of methyl-tert-butyl ether to freshwater organisms. AB - Increased input of the fuel oxygenate methyl-tert-butyl ether (MTBE) into aquatic systems has led to concerns about its effect(s) on aquatic life. As part of a study conducted by University of California scientists for the State of California, the Aquatic Toxicology Laboratory, UC Davis, reviewed existing literature on toxicity of MTBE to freshwater organisms, and new information was generated on chronic, developmental toxicity in fish, and potential toxicity of MTBE to California resident species. Depending on time of exposure and endpoint measured, MTBE is toxic to various aquatic organisms at concentrations of 57-> 1000 mg/l (invertebrates), and 388-2600 mg/l (vertebrates). Developmental effects in medaka (Oryzias latipes) were not observed at concentrations up to 480 mg/l, and all fish hatched and performed feeding and swimming in a normal manner. Bacterial assays proved most sensitive with toxicity to Salmonella typhimurium measured at 7.4 mg/l within 48 h. In microalgae, decreased growth was observed at 2400 and 4800 mg/l within 5 days. MTBE does not appear to bioaccumulate in fish and is rapidly excreted or metabolized. Collectively, the available data suggests that at environmental MTBE exposure levels found in surface waters (< 0.1 mg/l) this compound is likely not acutely toxic to aquatic life. However, more information is needed on chronic and sublethal effects before we can eliminate the possibility of risk to aquatic communities at currently detected concentrations. PMID- 11202719 TI - Manganese toxicity as indicated by visible foliar symptoms of Japanese white birch (Betula platyphylla var. japonica). AB - For the purpose of a field diagnosis of Mn toxicity, we showed the possibility of using visible foliar symptoms of Japanese white birch (Betula platyphylla var. japonica Hara) as indicator. To examine the relationship between the expression of visible symptoms and leaf Mn concentrations, white birch seedlings were grown under four different Mn levels: 1 mg Mn l-1 as control, 10, 50 and 100 mg Mn l-1. Foliar symptoms of Mn toxicity for white birch were: (1) chlorosis at entire young leaves in the 50 and 100 mg Mn l-1 treatments; and (2) brown speckles at the leaf marginal and interveinal area for old leaves in the treatments greater than 1 mg Mn l-1. Mn preferably accumulated into the leaf marginal and interveinal area, where the brown speckles were observed. The mechanism determining the expression of symptoms seems to be associated with the physiological state related to leaf age as well as Mn distribution and concentration within a leaf. PMID- 11202720 TI - Biomonitoring of sporadic acidification of rivers on the basis of release of preloaded cadmium from the aquatic bryophyte Fontinalis antipyretica Hedw. AB - A technique is proposed for biomonitoring of sporadic acidification events in rivers. Individuals of the bioindicator species are pre-incubated with a chemical marker, then transplanted to the test location for the period of interest, then analysed for marker content; acidification events are inferred on the basis of the degree of reduction in marker concentration. To assess the validity of the proposed technique, we performed laboratory trials with the aquatic bryophyte Fontinalis antipyretica Hedw. as bioindicator species, and cadmium (Cd) as marker. The bryophytes were pre-incubated with a Cd solution, obtaining saturation concentrations in the extracellular compartment and near-saturation concentrations in the intracellular compartment. In a first series of experiments, Cd-preloaded bryophyte apices were maintained for 1-30 h in water of different pH; the results clearly indicated that the amount of Cd released is dependent on pH. In a second series of experiments, Cd-preloaded bryophyte apices were maintained for 1-24 h in water with various combinations of pH and aluminium (Al) concentration (Al being a highly toxic element that is typically mobilized in acid waters). In these experiments, pH again had a marked effect on the amount of Cd released, while Al concentration had no consistent effects. To facilitate data analysis, Davidson-type equations were fitted to the results of the second series of experiments, allowing prediction of medium acidity on the basis of Cd concentration remaining in the extracellular and intracellular compartments. PMID- 11202721 TI - Chemical fingerprinting applied to the evaluation of marine oil pollution in the coasts of Canary Islands (Spain). AB - Chemical fingerprinting approach to environmental assessment is illustrated in the evaluation of marine oil pollution in the coasts using two limpet species as bioindicator organisms, and based on profiles and concentrations of n-alkanes and aromatic hydrocarbons in their tissues. Accidental and chronic releases of hydrocarbons can contaminate the marine environment of the Canary Islands not only because of their geographical situation but also because of the very dense tanker traffic around. This situation affects coastal areas, fishing activities, tourism resort, etc. Concentrations of n-alkanes and aromatic hydrocarbons (polycyclic aromatic hydrocarbons and methyl-polycyclic aromatic hydrocarbons) in the soft tissues of the marine intertidal and subtidal limpets, Patella crenata and Patella ullysiponensis aspera, were evaluated. Limpet samples were collected at monthly intervals, at three locations on the southeast coast of Tenerife over a 3-year period (1991-93). Levels of hydrocarbons found in limpets are similar to concentrations found in unpolluted areas around the world. From application of principal component analysis, the interpretation of variable loading plots gives information on variable correlation and can be used to distinguish among potential sources of pollution and the ability of studied molluscs to be used as bioindicator organisms. PMID- 11202722 TI - Quantification of bioavailable nickel in sediments and toxic thresholds to Hyalella azteca. AB - Bioaccumulation and chronic toxicity of nickel (Ni) to Hyalella azteca in Ni spiked sediments was strongly affected by the source of sediment used. The total range in LC50s on a sediment concentration basis ranged over 20 fold. Differences in Ni toxicity generally matched differences in Ni bioaccumulation, and toxicity expressed on a body concentration basis varied less than three fold. Body concentrations, therefore, provide a much more reliable prediction of Ni toxicity in sediments than do concentrations in the sediment. Ni in overlying water was also a reliable predictor of Ni toxicity, but only in tests conducted in Imhoff settling cones with large (67:1) water to sediment ratios. Overlying water LC50s for tests in beakers varied 18 fold. Sediment and body concentrations of Ni tolerated by Hyalella were slightly higher in cones than in beakers. Reproduction was not affected significantly by Ni at concentrations below the LC50 and 10-week EC50s for survival and biomass production (including survival, growth and reproduction) were only marginally lower than 4-week EC50s (survival and growth only). PMID- 11202723 TI - Stem injection of Populus nigra with EDU to study ozone effects under field conditions. AB - EDU or ethylenediurea (N-[2-(2-oxo-1-imidazolidinyl)ethyl]-N'-phenylurea) has been used in experiments to assess ozone effects on vegetation under field conditions because it provides protection against oxidative damage. Tests have mainly been conducted on crop plants, but for woody species only few reports have provided evidence that it can be used in long-term experiments. In this study we tested the technique of stem injection of EDU to study the effects of ozone exposure on Populus nigra cv. Wolterson over one growing season. Cuttings of Populus nigra were grown in pots in the field and between mid-July and early September plants were repeatedly injected with EDU solution (5 mg/plant) or with water at 14-day intervals. Significant differences were found between EDU- and water-injected plants: water-treated plants had more foliar injury, more chlorotic leaves, and shedding of leaves started earlier, suggesting EDU was effective in preventing visible ozone injury and acceleration of senescence. Photosynthetic rates, measured for one leaf age, showed no differences but were mostly higher for the EDU-treated plants. At the end of the growing season diameter increment was 16% higher and there was a non-significant trend for above ground biomass to be increased by 9% for the EDU-treated plants. This experiment has provided evidence that for this clone serious ozone damage occurs at relatively low concentrations and that EDU can provide protection against visible injury, as well as against longer term growth reductions. PMID- 11202724 TI - Dissipation of racemic mecoprop and dichlorprop and their pure R-enantiomers in three calcareous soils with and without peat addition. AB - Two racemic herbicides, mecoprop (R,S-MCPP) and dichlorprop (R,S-DCPP), as well as their enantiopure R-forms, were incubated in three calcareous soils at 15 degrees C and 80% of their field capacity to try to elucidate their behaviour in soil and compare the dissipation rates when racemic and enantiopure compounds are used. Quantitation of pesticides is made by HPLC and the R/S ratio by GC-MS. The inactive S-enantiomer from the racemic forms persists longer than the R-forms in silt and sandy loam soils, but for shorter time in the clay loam soil. The pure R enantiomers, both for MCPP and DCPP, after incubation in soil, are partially converted into their S-forms. In all cases, the dissipation of racemic and pure enatiomeric forms is lower in the clay loam soil than in the silt and sandy loam soils. The R-forms' peristence, in the three soils, is approximately two times lower when they are incubated alone than when they are incubated as racemic compounds. When peat is added, the persistence of these herbicides in the silt and sandy loam soils increases, while in the clay loam soil it decreases. Besides, in the clay loam soil, the enantiomeric ratio (ER) changes from its S preferential degradation to a preferential degradation of its R-form, so an increase in the persistence of the inactive S-form occurs. PMID- 11202725 TI - Factors controlling the bioaccumulation of mercury and methylmercury by the estuarine amphipod Leptocheirus plumulosus. AB - The bioaccumulation of inorganic mercury (HgI) and monomethylmercury (MMHg) by benthic organisms and subsequent trophic transfer couples the benthic and pelagic realms of aquatic systems and provides a mechanism for transfer of sedimentary contaminants to aquatic food chains. Experiments were performed to investigate the bioavailability and bioaccumulation of particle-associated HgI and MMHg by the estuarine amphipod Leptocheirus plumulosus to further understand the controls on bioaccumulation by benthic organisms. HgI and MMHg are particle reactive and have a strong affinity for organic matter, a potential food source for amphipods. Microcosm laboratory experiments were performed to determine the effects of organic matter on Hg bioaccumulation and to determine the major route of Hg uptake (i.e. sediment ingestion, uptake from water/porewater, or uptake from 'food'). Amphipods living in organic-rich sediment spiked with Hg accumulated less Hg than those living in sediments with a lower organic matter content. Feeding had a significant impact on the amount of HgI and MMHg accumulated. Similarly, amphipods living in water with little organic matter accumulated more Hg than those living in water with a greater percentage of organic matter. MMHg was more readily available for uptake than HgI. Experimental results, coupled with results from a bioaccumulation model, suggest that accumulation of HgI and MMHg from sediment cannot be accurately predicted based solely on the total Hg, or even the MMHg, concentration of the sediment, and sediment-based bioaccumulation factors. All routes of exposure need to be considered in determining the accumulation of HgI and MMHg from sediment to benthic invertebrates. PMID- 11202727 TI - Induction of mouthpart deformities in Chironomus riparius larvae exposed to 4-n nonylphenol. AB - Chironomid mouthpart deformities have often been associated with sediment contamination and are, therefore, currently used to assess sediment quality. Deformities were only occasionally induced in laboratory bioassays. Mouthpart deformities results from a physiological disturbance during larval molting. In the past few years it has been shown that some chemicals can exert negative effects on both vertebrates and invertebrates at the level of endocrine regulation. As insect molting is hormonally regulated, we wanted to test the hypothesis that deformities are induced due to a hormonal disruption in the developmental process. The aim of the present study was to test whether the endocrine disrupter, 4-n-nonylphenol (4NP), induces mouthpart deformities in chironomids. A laboratory bioassay was performed exposing Chironomus riparius larvae to 10, 50 and 100 micrograms l-1 4NP. Survival of the larvae was not affected by the tested concentrations, but the frequency of mentum deformities increased significantly (P < 0.01) after exposure to 4NP. PMID- 11202726 TI - Effects of major nutrient additions on metal uptake in phytoplankton. AB - We examined the influences of major nutrients (N, P, Si) on the accumulation of three trace metals [Cd, Se(IV), and Zn] in four species of marine phytoplankton (diatom, green alga, dinoflagellate, prasinophyte). Relative metal uptake was quantified by the kinetic measurements of metal concentration factor over a short exposure period. Our study demonstrated that nutrient addition significantly influenced the metal uptake rate and the cell growth rate in all four phytoplankton species. An increase in ambient N concentration considerably enhanced metal uptake by the cells. The dry weight concentration factor increased by 2.4-14.9 times for Cd, 1.1-4.0 times for Se, and 1.1-5.4 times for Zn in all four phytoplankton species with an addition of 176.4 microM N. The effects of P or Si addition on metal uptake and cell growth were less pronounced than the effects of N addition. Under most circumstances the rate of metal uptake increased exponentially with increasing cell growth rate constant. Only Se(IV) uptake in the diatom Phaeodactylum tricornutum was not correlated with cell growth rate. Se(IV) was not accumulated by the green algae Chlorella autotrophica at a high P concentration (7.2 microM), but appreciable accumulation was documented in cells inoculated without P addition. Our study therefore demonstrated that nutrient enrichments in many coastal waters can considerably affect trace metal uptake in phytoplankton and presumably metal trophic transfer in marine food chains. PMID- 11202729 TI - Investigations of ash topography/morphology and their relationship with heavy metals leachability. AB - The leachability of heavy metals such as chromium (Cr), lead (Pb) and cadmium (Cd) from the ash material obtained from waste combustion was studied. The effects of ash surface topography and morphology on the leachability of these elements were examined using atomic force microscopy (AFM) and scanning electron microscopy (SEM). The AFM (scan size 10 x 10 microns) and SEM images of the simulated ash pellet obtained at various operating temperatures (1000, 1400 and 1500 degrees C) showed significant microstructural and topographical changes. Ash pellets treated at 1000 degrees C contain porous and non-continuous surface. On the other hand, the ash pellet obtained at higher temperature (1500 degrees C) was found to contain a smooth, continuous and non-porous surface. The AFM height profile studies indicated that the top surface variation of the ash pellet at 1000, 1400 and 1500 degrees C were found to be -40.0 to 25.5, -3.7 to 4.7 and 0.10 to 0.66 nm respectively. The SEM analyses also confirmed the presence of smooth, non-porous outer surface of ash formed at 1500 degrees C. In addition, it also showed the presence of compact and rigid interior for the same ash pellet. The leachability of the heavy metals was determined using standard toxicity characteristic leaching procedure (TCLP) test and the samples were analysed using atomic absorption spectroscopy. The results showed that the TCLP leaching ratios of the heavy metals were Cr = 0.30, Pb = 0.05 and Cd = 0.09 at 1000 degrees C. However, the ash obtained at 1400 degrees C showed negligible heavy metals leaching ratio while at 1500 degrees C no leachability was detected (TCLP concentration dropped to nondetectable levels). The use of high temperature treatment enabled the immobilization of heavy metals in the ash preventing their leaching. Such ash can be considered as a non-hazardous material for reuse or safe disposal. PMID- 11202728 TI - Cadmium accumulation in the freshwater isopod Asellus racovitzai: the relative importance of solute and particulate sources at trace concentrations. AB - A stable isotope tracer technique was used to evaluate the relative importance of particulates and water as respective sources of cadmium (Cd) uptake in the freshwater isopod Asellus racovitzai (Isopoda, Crustacea). 113Cd(NO3)2 was applied to the sediment at a nominal concentration of 20.0 ng g-1, and 114Cd(NO3)2 was added to the overlying water (nominal concentration of 4.4 ng g 1), in the same test systems. Asellids added were either free-ranging on the sediment surface, where they were exposed to both particulate and water sources of Cd, or were enclosed in dialysis 'tubes', 10 cm above the sediment surface, and were therefore exposed to Cd in water only. By analysis of both isotopes, uptake vectors could be determined simultaneously. After 7 days of exposure, average 114Cd concentrations in 'free' asellids were 15.6 +/- 2.0 micrograms/g, compared with 10.4 +/- 1.8 micrograms/g in 'tube'-held asellids (P < 0.05), i.e. at least 60% of accumulated 114Cd was from water. Furthermore, water-spiked 114Cd was accumulated in asellids to tissue concentrations that were more than four times greater than sediment-spiked 113Cd. When the sediment organic content was increased (20% peat moss), total Cd concentrations in both overlying water and asellids were significantly lower (P < 0.01), compared with the mineral sediment treatments, and Cd accumulation in tube and free asellids was similar. This study shows that water is an important vector of Cd accumulation in A. racovitzai, and factors that lower Cd concentrations in solution (such as increased organic content of sediment), decrease Cd bioaccumulation. PMID- 11202730 TI - Nutrient dynamics and the eutrophication of shallow lakes Kasumigaura (Japan), Donghu (PR China), and Okeechobee (USA). AB - We compared the nutrient dynamics of three lakes that have been heavily influenced by point and non-point source pollution and other human activities. The lakes, located in Japan (Lake Kasumigaura), People's Republic of China (Lake Donghu), and the USA (Lake Okeechobee), all are relatively large (> 30 km2), very shallow (< 4 m mean depth), and eutrophic. In all three lakes we found strong interactions among the sediments, water column, and human activities. Important processes affecting nutrient dynamics included nitrogen fixation, light limitation due to resuspended sediments, and intense grazing on algae by cultured fish. As a result of these complex interactions, simple empirical models developed to predict in-lake responses of total phosphorus and algal biomass to external nutrient loads must be used with caution. While published models may provide 'good' results, in terms of model output matching actual data, this may not be due to accurate representation of lake processes in the models. The variable nutrient dynamics that we observed among the three study lakes appears to be typical for shallow lake systems. This indicates that a greater reliance on lake-specific research may be required for effective management, and a lesser role of inter-lake generalization than is possible for deeper, dimictic lake systems. Furthermore, accurate predictions of management impacts in shallow eutrophic lakes may require the use of relatively complex deterministic modeling tools. PMID- 11202731 TI - Comparison of two biological treatment processes using attached-growth biomass for sanitary landfill leachate treatment. AB - The objective of this investigation was to compare two biological systems using attached-growth biomass, for treatment of leachates generated in a typical municipal solid waste sanitary landfill. A moving-bed biofilm process, which is a relatively new type of biological treatment system, has been examined. It is based on the use of small, free-floating polymeric (polyurethane) elements, while biomass is being grown and attached as biofilm on the surface of these porous carriers. A granular activated carbon (GAC) moving-bed biofilm process was also tested. This method combines both physico-chemical and biological removal mechanisms for the removal of pollutants. The presence of GAC offers a suitable porous media, which is able to adsorb both organic matter and ammonia, as well as to provide an appropriate surface onto which biomass can be attached and grown. A laboratory-scale sequencing batch reactor (SBR) was used for the examination of both carriers. The effects of different operation strategies on the efficiency of these biological treatment processes were studied in order to optimize their performance, especially for the removal of nitrogen compounds and of biodegradable organic matter. It has been found that these processes were able to remove nitrogen content almost completely and simultaneously, the removal of organic matter (expressed as BOD5 and COD), color and turbidity were sufficiently achieved. PMID- 11202732 TI - Chronic toxicity of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) in soil determined using the earthworm (Eisenia andrei) reproduction test. AB - The sublethal and chronic effects of the environmental contaminant and explosive octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) in artificial soil were assessed using the earthworm (Eisenia andrei). Based on various reproduction parameters (total and hatched number of cocoons, number of juveniles and their biomass), fecundity was reduced at the different concentrations of HMX tested (from 280.0 +/- 12.3 to 2502.9 +/- 230.0 mg kg-1 dry soil) in spiked artificial soil (LOEC: 280.0 +/- 12.3 mg kg-1 dry soil). The growth of adult E. andrei was also reduced at the different concentrations tested, though no mortality occurred, even at the highest tested concentrations. The number of juveniles produced was correlated with the number of total and hatched cocoons, and the biomass of juveniles was correlated with the number of cocoons. Pooled results of these and earlier studies on explosives (TNT, RDX) using the E. andrei reproduction test confirm that effects of HMX on cocoon production are indicative of some reproductive consequences (number of juvenile and their biomass), whereas adult growth, in general, does not correlate strongly with change in reproduction capacity. PMID- 11202733 TI - Evaluation of copper availability to plants in copper-contaminated vineyard soils. AB - The repeated use of copper (Cu) fungicides to control vine downy mildew has led to long-term accumulation of Cu in vineyard soils which now raises the issue of the potential bioavailability of Cu for various living organisms including plant species. The bioavailable Cu can be defined as the portion of soil Cu that can be taken up by roots, for a given plant species. In order to evaluate the bioavailability of Cu to plants, a pot experiment was conducted in glasshouse conditions with a crop species (maize) and 12 soils sampled in the upper horizon of 10 vineyard plots (total Cu ranging from 38 to 251 mg kg-1) and two woodland plots (control soils that had not received any Cu application; total Cu amounting to 20-26 mg kg-1). These soils were selected for their diverse physical (large range of particle size distribution) and chemical (from acid to calcareous soils) properties. After 35 days of growth, plant shoots were harvested for analysis. The roots were separated from soil particles for further analysis. The concentrations of Cu in the roots and aerial parts of the maize were then compared with the amounts of Cu extracted from the soil by a range of conventional extractants. Observed Cu concentrations in maize roots which have grown in contaminated vineyard soils were very high (between 90 and 600 mg kg-1), whereas Cu concentrations in the aerial parts varied only slightly and remained low (< 18 mg kg-1). Root Cu concentrations observed for maize increased with increasing total Cu content in the soil and with decreasing soil CEC. Cu accumulation in maize roots may be as high in calcareous soils as in acid soils, suggesting that soil pH had little influence. In the case of the vineyard soils studied, the lack of correlation found for maize between Cu concentrations in roots and in the aerial parts, suggests that an analysis of the aerial parts would not be a good indicator of plant Cu uptake, as it provides no insight into the real amount of Cu transferred from the soil to the plant. For maize, our results show that extraction with organic complexing agents (EDTA, DTPA) and extraction with ammonium acetate seem to provide a reasonably good estimate of root Cu concentration. PMID- 11202734 TI - Sorption of naphthalene and phenanthrene by soil humic acids. AB - Humic acids are a major fraction of soil organic matter (SOM), and sorption of hydrophobic organic chemicals by humic acids influences their behavior and fate in soil. A clear understanding of the sorption of organic chemicals by humic acids will help to determine their sorptive mechanisms in SOM and soil. In this paper, we determined the sorption of two hydrophobic organic compounds, naphthalene and phenanthrene by six pedogenetically related humic acids. These humic acids were extracted from different depths of a single soil profile and characterized by solid-state CP/MAS 13C nuclear magnetic resonance (NMR). Aromaticity of the humic acids increased with soil depth. Similarly, atomic ratios of C/H and C/O also increased with depth (from organic to mineral horizons). All isotherms were nonlinear. Freundlich exponents (N) ranged from 0.87 to 0.95 for naphthalene and from 0.86 to 0.92 for phenanthrene. The N values of phenanthrene were consistently lower than naphthalene for a given humic acid. For both compounds, N values decreased with increasing aromaticity of the humic acids, such an inverse relationship was never reported before. These results support the dual-mode sorption model where partitioning occurs in both expanded (flexible) and condensed (rigid) domains while nonlinear sorption only in condensed domains of SOM. Sorption in the condensed domains may be a cause for slow desorption, and reduced availability and toxicity with aging. PMID- 11202735 TI - Measurement of symbiotic nitrogen-fixation in leguminous host-plants grown in heavy metal-contaminated soils amended with sewage sludge. AB - Rates of nitrogen fixation by Rhizobium in symbiosis with leguminous host-plants including white clover, broad bean and peas have been established in soils that have been amended experimentally with heavy metal-contaminated sewage sludges. Results from 15N-dilution experiments for the measurement of N2 fixation have shown that adverse heavy metal effects are apparent on symbiotic N2 fixation rates for white clover grown in inter-specific competition with ryegrass under mixed sward conditions, compared to white clover grown in pure sward. Further experiments on broad bean and pea indicated a significant, but minor-inhibitory metal-related effect on the rate of N2 fixation compared to untreated soils and soils amended with a relatively uncontaminated sludge. The implications of the results with respect to sludge utilisation in agriculture are discussed. PMID- 11202736 TI - Ozone exposure thresholds and foliar injury on forest plants in Switzerland. AB - Canton Ticino in southern Switzerland is exposed to some of the highest concentrations of tropospheric ozone in Europe. During recent field surveys in Canton Ticino, foliar symptoms identical to those caused by ozone have been documented on native tree and shrub species. In Europe, the critical ozone level for forest trees has been defined at an AOT40 of 10 ppm.h O3 (10 ppm.h accumulated exposure of ozone over a threshold of 40 ppb) during daylight hours over a six-month growing season. The objective of this study was to determine the amount of ambient ozone required to induce visible foliar symptoms on various forest plant species in southern Switzerland. Species were grown within eight open-top chambers and four open plots at the Vivaio Lattecaldo Cantonal Forest Nursery in Ticino, Switzerland. Species differed significantly in terms of the ppb.h exposures needed to cause visible symptoms. The most to least symptomatic species grown within open-plots in this study rank as Prunus serotina, Salix viminalis, Vibrnum lantana, Rhamnus cathartica, Betula pendula, Rumex obtusifolius, Sambucus racemosa, Morus nigra, Prunus avium, Fraxinus excelsior, Rhamnus frangula, Alnus viridis, Fagus sylvatica and Acer pseudoplatanus. Similar rankings were obtained in the non-filtered chamber plots. The ranking of species sensitivity closely follows AOT values for the occurrence of initial symptoms and symptom progression across the remainder of the exposure season. Species that first showed evidence of foliar injury also demonstrated the most sensitivity throughout the growing season, with symptoms rapidly advancing over ca. 25-30% of the total plant leaf surfaces by the end of the observation period. Conversely, those species that developed symptoms later in the season had far less total injury to plant foliage by the end of the observation period (1.5 to < 5% total leaf area injured). The current European ambient ozone standard may be insufficient to protect native plant species from visible foliar injury, and many more native species may be sensitive to ozone-induced foliar injury than are currently known. PMID- 11202737 TI - Phytoplankton responses to biomanipulated grazing pressure and nutrient additions -enclosure studies in unlimed and limed Lake Njupfatet, central Sweden. AB - Enclosure experiments aimed to assess the role of Chaoborus larvae in regulating lower trophic levels under natural and nutrient-enriched conditions were performed in situ in the dimictic, oligotrophic clearwater Lake Njupfatet, central Sweden. One experiment was performed before, and one after, whole-lake calcite treatment. In the acidic system, total planktonic biomass (TPB; the sum of phyto-, bacterio-, protozoo-, and metazooplankton), dominated by the cyanobacterium Merismopedia, was only weakly stimulated by the nutrients while the predator had no effect. In the limed environment, TPB increased strongly in response to the nutrients in combination with a negative response to the predator. Principally phytoplankton, but also bacterioplankton and protozooplankton (ciliates) were stimulated by the nutrients. It is argued that Merismopedia acted as a dead-end in the energy flow in the acidic system. Liming resulted in the disappearance of Merismopedia and this opened the flow of material to higher trophic levels. Since liming also led to a significant reduction in the concentrations of phosphorus in the lake water, it is proposed that a combination of liming and gentle fertilization might be used to restore the productivity of acidified lakes. PMID- 11202738 TI - The glutathione status of mature Scots pines during the third season of UV-B radiation exposure. AB - Impacts of UV-B radiation on the glutathione level were studied in mature Scots pine needles (Pinus sylvestris L.) during the third season of a UV-B field experiment. Studies were made on 4-week-old (July) to 14-week-old (September) current-year needles and 3-year-old needles which had their third UV-B-exposure season in progress. Depending on the season and the year (1996-98), the supplemental UV-B dose varied from 0.92 to 5.09 kJ m-2 day-1 UV-BBE compared to 0.47-2.44 kJ m-2 day-1 UV-BBE under the ambient treatment. Fully grown UV-B treated current-year needles showed lower total glutathione concentrations after the vegetation period in September, whereas in UV-B-treated 3-year-old needles the total glutathione content was significantly lower and the proportion of oxidized glutathione (GSSG%) 56% higher in July. The significant differences in total glutathione in current-year needles in September and in active 3-year-old needles in July seem to indicate that the effect of enhanced UV-B radiation on glutathione status could be cumulative. PMID- 11202739 TI - A new flux-orientated concept to derive critical levels for ozone to protect vegetation. AB - The current European critical levels for ozone (O3) to protect crops, natural and semi-natural vegetation and forest trees are based on a relative small number of open-top chamber experiments with a very limited number of plant species. Therefore, the working group "Effects of Ozone on Plants" of the Commission on Air Pollution Prevention of the Association of German Engineers and the German Institute of Standardization reanalysed the literature on O3 effects on European plant species published between 1989 and 1999. An exposure-response relationship for wild plant species and agricultural crops could be derived from 30 experiments with more than 30 species and 90 data points; the relationship for conifer and deciduous trees is based on 20 experiments with nine species and 50 data points. From these relationships maximum O3 concentrations for different risk stages are deduced, below which the vegetation type is protected on the basis of the respective criteria. Because it is assumed that the fumigation concentrations reflect the O3 concentrations at the top of the canopy, i.e. the upper surface boundary of the quasi-laminar layer if the micrometeorological big leaf approach is applied, the application of these maximum O3 concentrations requires the transformation of O3 concentrations measured at a reference height above the canopy to the effective phytotoxic concentrations at the top of the canopy. Thus, the approach described in this paper is a synthesis of the classical concept of toxicology of air pollutants (critical concentrations) and the more toxicological relevant dose concept. PMID- 11202740 TI - Saskatoon serviceberry and ambient sulfur dioxide exposures: study sites re visited, 1999. AB - Field surveys for symptoms of foliar injury in a regional airshed that is influenced by a number of point sources of SOx, NOx and hydrocarbons, combined with foliar and soil sulfur analyses, confirmed earlier results that Saskatoon serviceberry (Amelanchier alnifolia Nutt.) cv. Smokey can be used as a biological indicator of chronic sulfur dioxide exposures, in the presence of other phytotoxic air pollutants such as ozone. PMID- 11202741 TI - Microbial cellulose decomposition in soils from a rifle range contaminated with heavy metals. AB - The objective of this study was to assess the effects of heavy metals on microbial decomposition of cellulose in heavy metal-contaminated soils using a cotton strip assay. The assay is a measure of the potential of soil microorganisms to decompose the plant polymer, cellulose. Cellulolytic activity in soil was assessed by determining the reduction in tensile strength of the buried cotton strips over a 25- and 45-day period. Soils were obtained from a rifle range that contain high levels of lead, copper and zinc. The site has been used for approximately 50 years, resulting in metal levels of up to 30,000 mg/kg of lead, 4000 mg/kg of copper and 600 mg/kg of zinc in the most contaminated soils. All the metal-contaminated soils had lower degradation rates than the uncontaminated soils tested. Among the contaminated soils, however, the heavy metal concentration was not the major factor in determining the loss in tensile strength of the cotton strips, where cellulose decomposition was governed by other soil physicochemical properties. Soil with a higher cation exchange capacity, readily oxidisable material and volatile solids content had the greatest loss in tensile strength of cotton strips. Microbial adaptation to the presence of high concentrations of soil heavy metals and reduced bioavailability of metals is the likely explanation for this phenomenon. PMID- 11202742 TI - An integrative assessment of a watershed impacted by abandoned mined land discharges. AB - The Ely Creek watershed in Lee County, VA, USA, contains an abundance of abandoned mined land areas with acid mine drainage (AMD) that contaminate the majority of the creek and its confluence into Stone Creek. Acidic pH measurements ranged from 2.73 to 5.2 at several stations throughout the watershed. Sediments had high concentrations of iron (approximately 10,000 mg kg-1), aluminum (approximately 1,500 mg kg-1), magnesium (approximately 400 mg kg-1) and manganese (approximately 150 mg kg-1), and habitat was partially to non supporting at half of the stations due to sedimentation. Benthic macroinvertebrate surveys at six of 20 stations sampled in the watershed yielded no macroinvertebrates, while eight others had total abundances of only one to nine organisms. Four reference stations contained > or = 100 organisms and at least 13 different taxa. Asian clam in situ toxicity testing supported field survey results. Laboratory, 10-day survival/impairment sediments tests with Daphnia magna and Chironomus tentans and 48-h water column bioassays with Ceriodaphnia dubia indicated environmental stress to a lesser degree. Ten parameters that were directly influenced by AMD through physical, chemical, ecological and toxicological endpoints were assimilated into an ecotoxicological rating (ETR) to form a score of 0-100 points for the 20 sampling stations, and the lower the score the greater the AMD stress. Twelve of the 15 sampling stations influenced by AMD received an ETR score of 13.75-57.5, which were categorized as severely stressed (i.e. comprised the < 60 percentile category) and worthy of the highest priority for future ecological restoration activities in the watershed. PMID- 11202743 TI - Measurement of ethylene emission from Japanese red pine (Pinus densiflora) under field conditions in NOx-polluted areas. AB - Emission of ethylene from the needles of Japanese red pine, Pinus densiflora, was measured in air-polluted areas in Hiroshima, Japan. We applied a suitable protocol to determine the rate of ethylene emission from the excised needles. The influence of excision of needles on ethylene emission was not detected during the first 4 h of incubation at 20 degrees C. Ethylene emissions were low in the unpolluted (clean) areas regardless of the altitude or season. The emission of stress ethylene increased with the atmospheric NO2 concentration, suggesting that atmospheric NOx or related substances induced the higher ethylene emission in the polluted areas (near urban and industrial areas). In all cases, 1-year-old needles emitted significantly larger amounts of ethylene than the current needles. Ethylene emission did not increase evenly in the polluted areas, but the frequency of trees emitting high ethylene increased. Therefore, threshold rates for the baseline ethylene emission were proposed. PMID- 11202744 TI - Estimating the potential for ammonia emissions from livestock excreta and manures. AB - This paper reports a desk study to quantify the total-nitrogen (N) and ammoniacal N contents of livestock excreta, and to compare them with estimates of N losses to the environment from that excreta. Inventories of ammonia (NH3), nitrous oxide (N2O), dinitrogen (N2), and nitric oxide emissions (NO), together with estimates of nitrate (NO3-) leaching and crop N uptake were collated. A balance sheet was constructed to determine whether our estimates of N in livestock excreta were consistent with current estimates of N losses and crop N uptake from that N, or whether emissions of N compounds from livestock excreta may have been underestimated. Total N excretion by livestock in England and Wales (E&W) was estimated as 767-816 x 10(3) t of which 487-518 x 10(3) t was estimated to be total ammoniacal-N (TAN). Estimates of NH3 and N2O losses during housing and storage were derived from the difference between the total amount of TAN in excreta deposited in and around buildings, and the total amount of TAN in manure (i.e. the excreta deposited in and around buildings after collection and storage) prior to spreading and were ca. 64-88 x 10(3) t. The NH3-N emission from livestock buildings and manure storage in E&W quoted in the UK Emission Inventory (Pain et al., 1999. Inventory of Ammonia Emission from UK Agriculture, 1977. Report of MAFF contract WAO630, IGER, North Wyke) is ca. 80 x 10(3) t. Losses from NO3- leaching in the season after manure application and grazing were estimated as 73 and 32 x 10(3) t, respectively. Other gaseous losses of N were estimated as ca. 54 x 10(3) t. Crop uptake of manure N was estimated to be between 7 and 24 x 10(3) t. For manures, estimated N losses, immobilization and crop uptake total 326 x 10(3) t compared with estimates of 293-319 x 10(3) t TAN in excreta. Total N losses and crop uptake from TAN deposited at grazing were estimated to be 179-199 x 10(3) t compared with ca. 224 x 10(3) t TAN excreted. Thus all the TAN in manures appears to be accounted for, but ca. 25-45 x 10(3) t of TAN in urine deposited at grazing were not, and could be an underestimated source of gaseous emission or nitrate leaching. PMID- 11202745 TI - Spatial variability in the degradation rate of isoproturon in soil. AB - Thirty samples of soil were taken at 50-m intersections on a grid pattern over an area of 250 x 200 m within a single field with nominally uniform soil characteristics. Incubations of isoproturon (3-(4-isopropylphenyl)-1,1 dimethylurea) under standard conditions (15 degrees C; -33 kPa soil water potential) indicated considerable variation in degradation rate of the herbicide, with the time to 50% loss (DT50) varying from 6.5 to 30 days. The kinetics of degradation also varied between the sub-samples of soil. In many of them, there was an exponential decline in isoproturon residues; in others, exponential loss was followed by more rapid rates of decline; in a few soil samples, rapid rates of loss began shortly after the start of the incubations. In more detailed studies with soils from a smaller number of sub-sites (20), measurements were again made of isoproturon degradation rate, and the soils were analysed for organic matter content, pH, and nutrient status (N, P, K). Measurements were also made of isoproturon adsorption by the soils and of soil microbial biomass. Patterns of microbial metabolism were assessed using 95 substrates in Biolog GN plates. Soils showing rapid biodegradation were generally of higher pH and contained more available potassium than those showing slower degradation rates. They also had a larger microbial biomass and greater microbial metabolic diversity as determined by substrate utilisation on Biolog GN plates. The implications of the results for the efficacy and environmental behaviour of isoproturon are discussed. PMID- 11202746 TI - Risk based characterisation of contaminated industrial site using multivariate and geostatistical tools. AB - Human and ecological risk assessment requires the sources, distribution, mobility and environmental behaviour of contaminants to be investigated on a site-specific basis. It often deals with data sets which are relatively small and affected by sampling gaps. In the case of a polycyclic aromatic hydrocarbon (PAH) contaminated industrial site, Kriging interpolation of spatial data and principal component analysis (PCA) proved useful for extracting additional value from the data set. Kriging was adopted for assessing the horizontal and vertical distribution and transport of PAHs in soil. PCA was applied to PAH concentration and relative abundance in soil samples and interpreted on the basis of the PAH physico-chemical and bio-degradation properties. It revealed correlation with the products of a neighbouring factory and the weathering of the lighter PAHs. The geo- and multivariate statistical results were coupled with the previous hydrogeological characterisation of the site to develop a site-conceptual model for use in the exposure scenario modelling for risk assessment. PMID- 11202747 TI - Mobility of heavy metals as related to soil chemical and mineralogical characteristics of Brazilian soils. AB - In order to better understand the relationship between soil characteristics and mobility of some heavy metals, correlation studies were conducted in samples of unlimed and limed A, B and C horizons of three Brazilian soils, representative of the majority of the tropical soils. A number of chemical and mineralogical characteristics of one Oxisol and two Ultisols were related to the retardation factors (Rf) for zinc (Zn), cadmium (Cd), copper (Cu) and lead (Pb). The retardation factors, obtained in leaching column experiments, were used as an estimate of solute movement in the profile. Soil types and soil horizons were found to influence metal retardation factors which, in turn, correlated better with the chemical than the mineralogical soil characteristics. For the unlimed soil samples, the soil characteristics that significantly correlated with Zn-Rf and Cd-Rf were the sum of exchangeable bases (SB), and soil exchangeable (Ca-KCl) and non-exchangeable (Ca-HCl) calcium contents. These results showed the strong influence of the cation exchange phenomenon on the retention and mobility of these two metals. For Cu and Pb, not only SB, cation exchange capacity (CEC) and Ca-KCl and Ca-HCl but also the organic matter correlated well with the Rf, showing that complex or chelate formation may play an important role in the movement of these elements. The important soil chemical characteristics related to the retardation factors in the limed soil samples were SB for Cd, and Ca-HCl for Cu and Pb, suggesting that precipitation may also influence the mobility and retention of the latter two heavy metals in these soil samples. Soil pH influenced the heavy metals adsorption and movement as shown by the significant correlation with the retardation factors when the combined data for the unlimed and limed soil samples was considered. PMID- 11202748 TI - Induction of the P450 reporter gene system bioassay by polycyclic aromatic hydrocarbons in Ulsan Bay (South Korea) sediments. AB - Polycyclic aromatic hydrocarbons (PAHs) and induction of the P450 reporter gene system (RGS) for 6- and 16-h exposure periods were determined in organic extracts of Ulsan Bay (South Korea) sediments to assess the utility of this bioassay as a screening tool for PAH contamination. The sum of the concentrations of 23 individual PAHs in 30 sediment samples (sigma PAH) based on GC-MS analysis ranged from 0.05 to 6.1 micrograms/g dry wt. P450 RGS fold induction ranged from 4.0 to 320 micrograms/g based on benzo[a]pyrene toxic equivalents (BaPEq). P450 RGS BaPEq and the 'chemical BaPEq', defined as the sum of the products of individual PAH concentrations and pre-determined toxic equivalency factors, exhibited very strong positive correlations with sigma PAH (r2 > 0.90; P < 0.001). Fold induction did not increase (and in some cases decreased) after the optimal incubation period (6 h) for PAHs, indicating that other compounds known to induce the P450 RGS (e.g. chlorinated organics) were not present at levels effecting significant induction. This was supported by GC-ECD analysis where non-ortho and mono-ortho polychlorinated biphenyls (PCBs) known to be strong P450 RGS inducers were found to be at very low or non-detectable levels in samples with the highest P450 RGS responses. The profound difference in PAH profiles for the two most contaminated sites suggested that this assay is especially sensitive for selected PAHs with greater than four rings. Combined with previous results, the P450 RGS shows promise as a useful screening tool for predicting deleterious biological effects resulting from CYP1A1-inducing, sediment-associated chemicals, particularly high molecular weight PAHs. PMID- 11202749 TI - Bioaccumulation of butyltins in Dreissena polymorpha at a confined placement facility in Buffalo, New York. AB - This study involves a site characterization followed by biomonitoring with the zebra mussel, Dreissena polymorpha, at the Times Beach confined placement facility (CPF), located in Buffalo, NY. The contaminant of interest was tributyltin (TBT) and the degradation products dibutyltin (DBT) and monobutyltin (MBT). At study initiation (Day 0) TBT levels in the baseline mussels were 5.86 +/- 0.43 ng Sn/g, DBT levels were 2.25 +/- 0.37 ng Sn/g. No MBT was detected in the Day 0 baseline samples. Caged reference mussels placed back in the Black Rock Channel Lock and retrieved on Days 19 and 34 had TBT, DBT, and MBT levels which did not differ significantly from the Day 0 baseline levels. Mussels placed at the Times Beach CPF had TBT concentrations that were significantly lower at both Days 19 (3.65 +/- 0.90 ng Sn/g) and 34 (3.50 +/- 1.03 ng Sn/g) than the Day 0 baseline analysis (5.86 +/- 0.43 ng Sn/g). The results of this study indicate that butyltins were detected at the CPF site in the sediment (7.33 +/- 5.70 ng Sn/g) but not the water column (not detected at 0.01 microgram/l). In this study the zebra mussel was able to depurate TBT even in the presence of contaminated sediment. TBT may be bioaccumulated from the sediments. However, the initial levels in the mussels were so high, levels actually dropped as sediment-tissue equilibria levels were reached by the mussels. PMID- 11202750 TI - Effect of chlorsulfuron on growth of submerged aquatic macrophyte Potamogeton pectinatus (sago pondweed). AB - Research has been conducted on the effect of chlorsulfuron on non-target plants but little information is available on its effects on aquatic macrophytes. Potamogeton pectinatus (sago pondweed) is an ecologically important submerged aquatic macrophyte found in freshwater bodies. Many species of wildlife use this plant as a food source. The objective of this study was to measure the phytotoxic effects of chlorsulfuron on sago pondweed. P. pectinatus plants were exposed to chlorsulfuron at 0, 0.25, 0.50, 1.0, or 2.0 ppb, in an environmental growth chamber. Plants exposed to 0.25 ppb chlorsulfuron showed a reduction in length (76%), number of leaves (50%), and number of stems (50%), compared to control plants. A reduction (47%) was also observed in the length of stems produced by plants treated with > or = 0.50 ppb chlorsulfuron. Significant reductions in wet and dry weights, and increased mortality were observed on treatments with > or = 1.0 ppb chlorsulfuron. PMID- 11202752 TI - Air pollution modeling for an industrial complex and model performance evaluation. AB - Jamshedpur, the steel city of India situated in the eastern part of India is affected by increasing air pollution levels as a result of concentrated industrial activities. The impact of NOx emissions resulting from various air pollution sources, viz. industries, vehicles and domestic, was estimated using Industrial Source Complex Short-Term gaussian dispersion model. The contribution of NOx concentration from industrial, vehicular and domestic sources was found to be 53, 40 and 7%. Further statistical analysis was carried out to evaluate the model performance by comparing measured and predicted NOx concentrations. The model performance was found good with an accuracy of about 68%. PMID- 11202751 TI - The otter (Lutra lutra) in Sweden--population trends in relation to sigma DDT and total PCB concentrations during 1968-99. AB - Polychlorinated biphenyl (PCB) has been suggested as the major cause of the European otter (Lutra lutra) population decline. This study investigates temporal and geographical changes in otter numbers as well as total PCB and sigma DDT concentrations in otters and their food in different parts of Sweden with various pollution impacts during three decades. In Sweden, rare species belong to the State and carcasses of such specimens are sent to the authorities. Two-hundred and eight specimens have been used to investigate temporal and spatial variation in the otter populations during 1968 and 1999. One-hundred and twenty-five of them have been chemically analysed. The population trends in northern Sweden coincide with the temporal trends of the contaminants. When concentrations of PCBs decrease in the environment, otter population increases. Neither aldrin/dieldrin nor mercury pollution seem to explain why the Swedish otter populations decreased dramatically during the 1960s-1980s. In southern Sweden total PCB concentrations are still high and the indications of improvement of the population are weak. PMID- 11202753 TI - Effects of elevated carbon dioxide and ozone on the growth and yield of potatoes (Solanum tuberosum) grown in open-top chambers. AB - Potato (Solanum tuberosum cv. Bintje) was grown in open-top chambers under three carbon dioxide (ambient and seasonal mean concentrations of 550 and 680 mumol mol 1 CO2) and two ozone concentrations (ambient and an 8 h day-1 seasonal mean of 50 nmol mol-1 O3) between emergence and final harvest. Periodic non-destructive measurements were made and destructive harvests were carried out at three key developmental stages (24, 49 and 101 days after emergence) to establish effects on growth and tuber yield. Season-long exposure to elevated O3 reduced above ground dry weight at final harvest by 8.4% (P < 0.05), but did not affect tuber yields. There was no significant interaction between CO2 and O3 for any of the growth and yield variables examined. Non-destructive analyses revealed no significant effect of elevated CO2 on plant height, leaf number or green leaf area ratio. However, destructive harvests at tuber initiation and 500 degrees Cd after emergence showed that above-ground dry weight (8 and 7% respectively) and tuber yield (88 and 44%) were significantly increased (P < 0.05) in the 550 mumol mol-1 CO2 treatment. Responses to 550 and 680 mumol mol-1 CO2 were not significantly different for most parameters examined, suggesting the existence of an upper limit to the beneficial influence of CO2 enrichment. Significant effects on above-ground dry weight and tuber yield were no longer apparent at final harvest, although tuber numbers were increased (P < 0.05) under elevated CO2, particularly in the smaller size categories. The results show that the O3 treatment imposed was insufficient to reduce tuber yields and that, although elevated CO2 enhanced crop growth during the early stages of the season, this beneficial effect was not sustained to maturity. PMID- 11202754 TI - Mercury, cadmium, lead and selenium in ringed seals (Phoca hispida) from the Baltic Sea and from Svalbard. AB - The concentrations of mercury (Hg), cadmium (Cd), lead (Pb) and selenium (Se) were determined in liver, kidney and muscle samples from 20 Baltic ringed seals (Phoca hispida botnica) (3-32 years), and from 17 ringed seals (Phoca hispida) (0 20 years) from Svalbard, in the Arctic. The concentrations of Hg and Se were considerably higher in the Baltic ringed seals, but the Cd concentrations lower than in the Svalbard ringed seals. There was no big geographical difference with respect to Pb concentrations. Se and Hg concentrations showed a significant positive correlation in both regions. By comparison with earlier studies on Baltic seals, the metal concentrations have remained at the same level since the 1980s. Of the metals we studied, only the level of Hg in Baltic ringed seals can be considered high (mean 53 mg/kg, range 6.5-124 mg/kg wet wt. for liver), but probably not high enough to cause metal intoxication. No pathological changes associated with metal intoxication were observed in the seals. PMID- 11202756 TI - Cuban Health System offers an uncommon opportunity. PMID- 11202755 TI - The use of amino compounds for binding 2,4,6-trinitrotoluene in water. AB - Sites polluted with 2,4,6-trinitrotoluene (TNT) constitute a worldwide problem. In this work, chemical reactions for binding TNT to amino-compounds are proposed as an initial step for developing new remediation techniques to clean-up groundwater and soils contaminated with TNT. Indeed, addition of aniline and an amino acid-like cysteine caused a decrease in free TNT of 86% and 68-100%, respectively. Using 13C-NMR spectroscopy, it was shown that TNT chemically forms a Meisenheimer complex with cysteine and aniline in 1/1 (by vol.) H2O/d6-acetone. PMID- 11202757 TI - Psychometric properties of the VSQLQ in black patients with mild hypertension. Vital Signs Quality of Life Questionnaire. AB - The Vital Signs Quality of Life Questionnaire (VSQLQ) is a condition- and culture specific measure designed to assess health-related quality of life (HRQL) in black patients with hypertension. This study examined the instrument's reliability and validity when administered via personal interview to patients with mild systemic hypertension. Data were gathered from 304 black patients during the screening visit of a multicenter trial evaluating the efficacy of candesartan cilexetil (ATACAND). In addition to internal consistency and reproducibility, validity was assessed by correlating the VSQLQ with the Short Form-36 (SF-36). Sensitivity to sociodemographic effects and responsiveness to change was also examined. Cronbach's alpha levels were high (0.90, 0.92, 0.92 for frequency, intensity and combined scores, respectively) and the instrument was stable in patients reporting no health change over 8 weeks (ICC = 0.79, 0.79, and 0.80). Correlations between the VSQLQ and the SF-36 were moderate to high (0.32 to - 0.69) and statistically significant (p < 0.001). VSQLQ scores varied by gender, education, and income (p < 0.05). Patients who reported improvement in their general health status also reported significant improvements on the VSQLQ (n = 90; p < 0.05). Results support the reliability and validity of VSQLQ administered via personal interview to black patients with mild systemic hypertension. PMID- 11202758 TI - African-American teen smokers: issues to consider for cessation treatment. AB - Previous reports have indicated ethnic differences in both tobacco-related morbidity and treatment outcome for smoking cessation among adults. We assessed smoking-related characteristics in African-American and non-African American teenagers applying to a cessation trial. 115 teens (15.9 +/- 1.8 years, 68% females, 27% African-American) responded via telephone to media ads. Self reported sociodemographic, medical and smoking-related data were obtained to determine pre-eligibility for a full intake screen prior to trial participation. Compared to non-African American, African American teen applicants were older (16.4 +/- 1.7 years versus 15.6 +/- 1.6; p = 0.015), had lower Fagerstrom Test for Nicotine Dependence (FTND) scores (5.3 +/- 2.3 versus 6.1 +/- 1.8; p = 0.018, ANOVA controlling for age) and smoked fewer cigarettes on the weekend (27 +/- 16 versus 38 +/- 17; p = 0.001). African American teens reported similar duration of smoking (3.3 +/- 1.4 versus 3.1 +/- 1.5 years) and time elapsed between first cigarette ever smoked and daily smoking (0.7 +/- 0.9 versus 0.6 +/- 0.7 years). African American and non-African American teens had similar motivation to quit scores and frequency of reported health problems (e.g., asthma, psychiatric conditions). These data suggest that cessation treatment programs designed for African American youth should include lower Fagerstrom-defined levels, and possibly other criteria for tobacco dependence. These observations also highlight the importance of ethnocultural issues in treatment research programs. PMID- 11202759 TI - Knowledge of the Tuskegee study and its impact on the willingness to participate in medical research studies. AB - The under-representation of racial/ethnic minorities among medical research participants has recently resulted in mandates for their inclusion by the National Institutes of Health (NIH). Therefore, there is a need to determine how history, attitudes, cultural beliefs, social issues, and investigator behavior affect minority enrollment in medical research studies. From January 1998 to March 1999, 179 African-American and white residents of the Detroit Primary Metropolitan Statistical Area (PMSA) participated in a mail and telephone survey designed to examine impediments to African-American participation in medical research studies. Chi-square tests were performed to assess differences between the study groups using the Survey Data Analysis Program (SUDAAN). Eighty-one percent of African Americans and 28% of whites had knowledge of the Tuskegee Study (p = <0.001). Knowledge of the Tuskegee Study resulted in less trust of researchers for 51% of African-Americans and 17% of whites (p = 0.02). Forty-six percent of African-Americans and 34% of whites indicated that their knowledge of the study would affect future research participation decisions (p = 0.25). Of these, 49% of African-Americans and 17% of whites would not be willing to participate in future medical research studies (p = 0.05). This study confirms the need for medical researchers to confront the issue of the Tuskegee Study and its continuing impact on African-Americans' trust of medical research studies. PMID- 11202760 TI - Economic and outcomes assessment of magnetic resonance imaging in the evaluation of headache. AB - We sought to evaluate the economic impact and diagnostic utility of magnetic resonance imaging (MRI) in the management of patients with headache and nonfocal physical examinations. Computerized medical records were retrospectively reviewed of 1,233 patients presenting for MRI of headache at our institution over a 3-year period (1992-1995). Patients with focal findings at physical examination, prior brain surgery, head trauma, or immunocompromise were excluded. A model was developed to assess the cost associated with the MR test results, and actual average institutional costs of performing an examination applied. Correlative statistical analysis of referring specialties and positive tests was also performed. Three hundred twenty-eight patients who met the above criteria were retained in the sample. One hundred sixty-three patients (50%) had negative MR test results. Of the 50% of patients with positive studies, only 5 (1.5%) had clinically significant MR results. The average cost of an MR examination was 517 dollars (1998 dollars). The cost per clinically significant managed case detected was 34,535 dollars. No statistically significant difference was found among referring specialties and clinically significant MR results. Our results indicate that MRI of nonfocal headache yields a low percentage of positive clinically significant results and has limited cost-effectiveness. Referring specialty had no significant bearing on these outcomes, regardless of specialist experience. PMID- 11202762 TI - Percutaneous injuries in a high-volume podiatric surgical residency program. AB - Percutaneous injuries (i.e., needlesticks) are a possible occupational hazard to all residents performing invasive procedures. Transmission of blood-borne pathogens has become a potential risk in these injuries. As such, the purpose of this investigation was to assess the frequency and circumstances involving percutaneous injuries in the podiatric surgical resident. A survey of 20 present residents from July 1991 to July 1999 was conducted to assess percutaneous injuries. These residents participated in 19,505 surgical cases in this timeframe; 16,185 were podiatric cases and 3,347 were nonpodiatric. Using a two part questionnaire to assess the circumstances surrounding any percutaneous injury, 80% of the residents reported at least one percutaneous injury during their training. A total of 33 were injuries reported for the 19,505 cases. The incidence of injury per surgical case was 0.17% overall, and 0.14% for foot and ankle cases. Analysis of the data showed a median = 2, mode = 2, and a mean = 1.63 injuries per resident with a range of 0-5. When analyzing the circumstances involving the injuries, most injuries were self-inflicted (66.7%), occurred during wound closure (72.7%), and were caused by a nonhollow bore needle or instrument (81.8%). Also, no correlation could be made to the time of day during which the procedure was performed, the year of residency training, or the number of cases that the resident performed that day before the injury occurred. Interestingly, over 67% of the injuries occurred to the resident's left hand. Although 97% of the injuries were reported to the employee health officer, the patient and resident were screened for HIV and hepatitis B or C in only 78.8% of the cases. In those tested, no resident was exposed to HIV or hepatitis B or C. PMID- 11202761 TI - Osteoradionecrosis of the mandible. AB - Osteoradionecrosis is a major complication of surgery or trauma in previously irradiated bone in the absence of tumor persistence. Radiation-induced vascular insufficiency rather than infection causes bone death. It occurs most commonly in the mandible after head and neck irradiation. Risk factors include the total radiation dose, modality of treatment, fraction size and dose rate, oral hygiene, timing of tooth extractions as well as the continued use of tobacco and alcohol. This condition is often painful, debilitating, and may result in significant bone loss. The recommended treatment guidelines are irrigation, antibiotics, hyperbaric oxygen therapy, and surgical techniques, including hemimandibulectomy and graft placements. PMID- 11202763 TI - In situ tibialis posterior to flexor digitorum longus tendon transfer for tibialis posterior tendon dysfunction: a simplified surgical approach with outcome of 11 patients. AB - Outcomes for 11 patients who underwent an in situ tibialis posterior tendon to flexor digitorum longus tendon side-to-side anastamosis as the sole procedure for stage 2 tibialis posterior tendon dysfunction were reviewed. The average follow up was 34.4 months. Using the American Orthopedic Foot and Ankle Society hindfoot rating scale, a mean improvement of 39.3 points was achieved, with preoperative scores of 38.8 improving to 78.1 postoperatively. Good to excellent results were achieved in nine patients. The in situ side-to-side anastamosis is technically easier to perform, has less tissue trauma, and compares favorably with other soft tissue procedures and reconstructions for stage 2 tibialis posterior tendon dysfunction. Performing this transfer alone, while leaving the flexor digitorum longus tendon intact, theoretically provides a stronger transfer as the length tension relationship of the flexor digitorum longus tendon is maintained near its physiologic level. The procedure can consistently restore inversion ability to the rearfoot and stop the progression of tibialis posterior tendon dysfunction. PMID- 11202764 TI - Plantar fat pad atrophy: a cause of metatarsalgia? AB - The aim of this prospective study was to evaluate if atrophy of the plantar fat pad in splay-foot deformities was a major cause of metatarsalgia. A sonographic method of measuring the thickness of the plantar fat pad under the second and third metatarsal heads was developed. The method was tested on 25 volunteers and the intraobserver reliability was calculated to be 97.1% for the second metatarsal and 96.7% for the third metatarsal. Sonographic measurement of the plantar fat pad was then performed on 100 symptomatic feet Pain frequency and pain intensity were determined by using a verbal rating scale (VRS) and a visual analog scale (VAS). The intermetatarsal angle 1/2 was measured and then compared to the thickness of the fat pad for each patient. A correlation between the increase of the intermetatarsal angle and the decrease of the fat pad thickness could not be demonstrated (r = 0.041). The frequency of metatarsalgia did not correlate with a decrease of the thickness of the plantar fat pad under the second metatarsal head (t statistic: 1.978; Durbin-Watson test: 1.999; p value = .0507) and the third metatarsal head (t statistic: 3.199; Durbin-Watson test: 1.962; p value = .0019). The pain intensity showed a similar lack of correlation with the thickness of the plantar fat pad under the second metatarsal head (t statistic: 1.828; Durbin-Watson test: 2.365; p value = .0706) and the third metatarsal head (t statistic: 1.846; Durbin-Watson test: 2.371; p value = .0678). This study shows that a splay-foot deformity is not associated with a decrease of the thickness of the plantar fat pad. Furthermore, alterations of the thickness of the plantar fat pad are not relevant to the intensity and frequency of metatarsalgia. PMID- 11202765 TI - Primary soft-tissue neoplasms of the foot: the clinicopathologic features of 401 cases. AB - Neoplasms of the soft tissue range from benign, indolent tumors to some of the most aggressive malignancies known to man. Despite exhaustive studies detailing their occurrence elsewhere within the body, there has been relatively little detailing such neoplasms arising within the soft tissues of the foot. Due to the relative infrequency with which malignant soft-tissue tumors occur in the foot, large series pertaining to this location have been difficult to assemble. To better elucidate the relative frequency of various benign and malignant soft tissue tumors of the foot, the clinicopathologic features of 401 such neoplasms are described. All cases were retrieved from the files of a major medical center which specializes in the treatment of cancer. Of the 401 cases identified, 149 were benign, while 252 cases were of a malignant nature. The clinicopathologic features are summarized and descriptive statistics are applied. Special focus is given to the discussion of the malignant and rare tumors within this series. Recent concepts regarding diagnosis, prognosis, and therapy are similarly discussed. PMID- 11202766 TI - Combined cryotherapy/70% salicylic acid treatment for plantar verrucae. AB - Although common, warts are inconsistently treated by any single method. The authors present a review of the literature for various treatments with regard to the methodology and success rate of each treatment modality. The authors also present a therapeutic regimen of combined cryotherapy/ 70% salicylic acid. This treatment involves in-office application of the cryogenic agent and daily application of 70% salicylic acid by the patient. The cryotherapy was combined with daily patient application of salicylic acid to increase destruction of the verruca. In a study of 29 patients with 65 warts, the authors found this method successful in 58 warts in 25 patients, showing a 89.2% rate of eradication of verrucae in 86.2% of patients. The method is recommended due to its consistent efficacy in the patient population, and its relatively gentle and noninvasive approach. PMID- 11202768 TI - Chip fractures of the first metatarsal head. Primary fragment excision versus immobilization: a report of four cases. AB - Four cases of a distal lateral impaction fracture of the first metatarsal are presented. Two treatment schemes were implemented. In two of the patients the fracture fragment was removed early. The other two patients had either percutaneous pinning or a weightbearing cast Each case discusses the rationale for the selected treatment as well as the clinical outcome. All four patients ultimately had successful retums to full activity with a more immediate return to exercise for the two patients with excised fracture fragments (6-week difference). PMID- 11202767 TI - Complex foot deformities associated with soft-tissue scarring in children. AB - Two cases of deformities in scarred feet are presented. One case had an old, well healed forefoot amputation with severe equinovarus deformity, and the other had an equinus deformity following a burn injury 10 months prior. Both the cases were managed by primary release of the contracted joint capsules. The correction of the soft-tissue contractures was achieved by gradual distraction using the Ilizarov apparatus. The clinical presentation and surgical treatment of complex foot deformities, complicated by the presence of scar tissue, are presented. These cases illustrate the benefits of combining soft-tissue release with the Ilizarov technique of distraction histogenesis in the treatment of complicated foot deformities associated with scarring in pediatric patients. PMID- 11202769 TI - The Evans osteotomy: technique and fixation with cortical bone pin. AB - The use of a lamina spreader over converging pins facilitates opening of an Evans calcaneal osteotomy and allows for precise measurement of the recipient site. The technique of cortical bone pin insertion has been utilized when indicated by the authors a limited number of times (N = 10) and as such this will be the subject of a future scientific investigation. The authors feel the advantages of the cortical bone pins include ease of use, good resultant stability of the capital fragment, utilization of a material identical to that of the correcting graft, a more biologic form of absorbable internal fixation, and the avoidance of complications associated with percutaneous metallic fixation (Fig. 5). PMID- 11202770 TI - Youngswick-Austin procedure: the effect of plantar arm orientation on metatarsal head displacement. AB - The Youngswick-Austin metatarsal head procedure was developed to allow for correction of a mildly elevated metatarsal head and/or to shorten an abnormally long first metatarsal. However, it was difficult to accurately and consistently predict the amount of plantar metatarsal head displacement utilizing this modification of the Austin procedure. This study demonstrated, through the use of preoperative templates and a mathematical formula, that the angle of the plantar arm relative to the weightbearing surface of the foot is what dictates the amount of plantar metatarsal head displacement. The authors divide the angle of the chevron osteotomy into a dorsal and plantar arm angle and demonstrate that the larger the angle of the plantar arm, the greater one can plantarly displace the metatarsal head. PMID- 11202771 TI - The medicalization of women's sexuality. PMID- 11202772 TI - Hepatitis C. PMID- 11202773 TI - Hepatitis C. PMID- 11202774 TI - Mothers and methadone. PMID- 11202775 TI - The AMA takes umbrage. PMID- 11202776 TI - Air Force may change nurse corps admission standards. PMID- 11202777 TI - State of the nursing shortage. PMID- 11202778 TI - A victory for nurses. Needlestick prevention legislation is passed by Congress and signed into law. PMID- 11202779 TI - Complex regional pain syndrome. PMID- 11202780 TI - Hidden factors in occult blood testing. Foods and medications can affect results. PMID- 11202781 TI - Stable & able. A standardized nursing intervention protocol for patients with cancer redefines the relationship among patients, caretakers, and nurses. PMID- 11202782 TI - Emergency: Bioterrorism. PMID- 11202783 TI - Sexual counseling after myocardial infarction. PMID- 11202784 TI - Vacuum-assisted wound closure. PMID- 11202785 TI - Advance directives. PMID- 11202786 TI - A nurse's lifeline. A nursing ethics committee offers the chance to review and learn from ethical dilemmas. PMID- 11202787 TI - Post-polio syndrome. PMID- 11202788 TI - 'One pill makes you larger...'. Don't be seduced by pharmaceutical companies. PMID- 11202789 TI - A healthy environment for a healthy community. Initiating the '2,000 trees for 2000' campaign. PMID- 11202790 TI - A national uprising. United actions push mandatory overtime, inadequate staffing to forefront. PMID- 11202791 TI - Your final warning. Know your rights in advance of a layoff. PMID- 11202792 TI - Breast cancer survival and hormone replacement therapy: a cohort analysis. AB - Controversy exists regarding the safety of hormone replacement therapy (HRT) after a diagnosis of breast cancer. The objective of this study is to perform a matched cohort analysis to evaluate the impact of HRT on mortality in breast cancer survivors. Patients with breast cancer who received HRT after diagnosis of breast cancer were identified. Control subjects were identified from the regional cancer registry. Matching criteria included age at diagnosis, stage of breast cancer, and year of diagnosis. Controls were selected only if they were alive at the time of initiation of HRT of the matched case. Only subjects not included in a previously reported matched analysis were selected. One hundred twenty-five cases were matched with 362 controls. Ninety-eight percent (123/125) of the cases received systemic estrogen; 90/125 (72%) also received a progestational agent. The median interval between diagnosis of breast cancer and initiation of HRT was 46 months (range 0-401 months). The median duration of HRT was 22 months (range 1 357 months). The risk of death was lower among the HRT survivors; odds ratio 0.28 (95% confidence interval 0.11-0.71). This analysis does not suggest that HRT after the treatment of breast cancer is associated with an adverse outcome. PMID- 11202793 TI - Angiogenesis and p53 protein expression in breast cancer: prognostic roles and interrelationships. AB - The authors have analyzed, on the one hand, the prognostic impact of microvessel density (MVD) and p53 protein expression in patients with breast cancer, and on the other hand, the correlation between the microvascular pattern and the p53 protein expression. Tumors from 120 patients whose paraffin-embedded tissue blocks were available were analyzed using the immunohistochemical method. MVD and p53 protein expression were correlated with histologic grade and tumor size, respectively. The patients with highly vascularized tumor (high MVD) had decreased overall survival (p = 0.04), whereas overexpressed p53 patients did not. In multivariate analysis, axillary lymph node status (p = 0.007), tumor size (p = 0.01), and MVD (p = 0.02) showed important prognostic influence on overall survival. When the simultaneous influence of MVD and p53 protein expression on survival were analyzed, no interrelationship was detected. The results demonstrate the prognostic impact of MVD on overall survival in breast cancer and no association between MVD and p53 protein expression. PMID- 11202794 TI - Analysis of the role of adjuvant chemotherapy for invasive carcinoma of the esophagus. AB - The purpose of this report is to analyze the role and optimum integration of chemotherapy for invasive carcinoma of the esophagus in the combined modality setting. The charts of 157 patients with primary invasive nonmetastatic carcinoma of the esophagus treated with curative intent between 1984 and 1998 were reviewed. Various combinations of chemotherapy (C), radiotherapy (R), and surgery (S) were used. Chemotherapy was multiagent (typically 5-fluorouracil [5 FU]/cisplatin/hydroxyurea, 5-FU/cisplatin/leucovorin, or docetaxel/cisplatin) for all but seven patients treated with single agents. The clinical endpoints examined were overall survival (OS) and cause-specific survival (CSS). Multivariate analyses and pairwise comparisons were made for determination of the benefit of chemotherapy. On the multivariate analyses, only American Joint Committee on Cancer stage and chemotherapy were statistically significant determinants of both OS and CSS. Following are the results of the pairwise analyses: 3-year OS: (no C) versus (any C): 16% versus 27% (p = 0.02); (S) versus (C+S): 19% versus 34% (p = 0.35); (R) versus (C+R): 0% versus 13% (p = 0.05); (R + S) versus (C + R + S): 18% versus 33% (p = 0.03). The administration of adjuvant chemotherapy can improve survival in patients with invasive nonmetastatic esophageal carcinoma. This benefit appears to be greater when chemotherapy is given with radiotherapy (with or without surgery) than in the absence of radiotherapy, perhaps because of a radiosensitizing effect not possible when using surgery is the only local control modality. PMID- 11202795 TI - Postoperative endoscopic retrograde high dose-rate brachytherapy for cholangiocarcinoma. AB - Cholangiocarcinoma typically presents with disease unlikely to be completely resected, and prognosis remains poor. Improvements in imaging, endoscopy, and stenting have given rise to renewed interest in brachytherapy. Several recent retrospective series suggest a benefit to intraluminal brachytherapy, most commonly delivered by the transhepatic route. We describe a case in which brachytherapy was delivered via the nasobiliary route to address positive margins at the common bile duct stump. A custom catheter was manufactured to make the procedure feasible. Pertinent literature is reviewed, which supports the view that these malignancies benefit from high doses of radiation, if this can be achieved respecting normal tissue tolerance. PMID- 11202796 TI - Chronic systemic (hepatosplenic) candidiasis in a patient with granulocytic sarcoma. AB - Chronic systemic (hepatosplenic) candidiasis (CSC) is a syndrome of invasive candidiasis characterized by fever without localizing signs or symptoms. It occurs predominantly in patients with acute leukemia, after prolonged severe neutropenia. We report a young woman who underwent extensive chemotherapy for granulocytic sarcoma of the ovary; CSC then developed in this patient. She was successfully treated with fluconazole and liposomal amphotericin B. Clinical presentation, diagnostic problems, and the current successful treatment with fluconazole and liposomal amphotericin B are discussed. PMID- 11202797 TI - Long-term results of lipiodol-transcatheter arterial embolization with cisplatin or doxorubicin for unresectable hepatocellular carcinoma. AB - The long-term effects of Lipiodol-transcatheter arterial embolization (Lp-TAE) combined with cisplatin (CDDP) or doxorubicin (ADM) on unresectable hepatocellular carcinoma (HCC) were analyzed. Eighty-four consecutive patients with unresectable HCC were treated with TAE. Of the 84, 38 patients were treated with CDDP-Lp-TAE (CDDP group), whereas the remaining 46 patients were treated with ADM-Lp-TAE (ADM group). No significant difference in characteristics of patients and tumors was noted between the groups. CDDP (50 mg) or ADM (20-50 mg) was administered with Lp followed by embolization of the feeding arteries using gelatin sponge particles. The mean number of TAE treatments was 3.3 in the CDDP group and 1.9 in the ADM group (p < 0.01). The 5-year overall survival rates of the CDDP group and the ADM group were 19% and 6%, respectively. The overall survival rate of the CDDP group was significantly higher than that of the ADM group (p < 0.05). No serious side effects were observed in either group. CDDP-Lp TAE improved the prognosis of unresectable HCC compared with ADM-Lp-TAE, which may be attributable to the fact that CDDP-Lp-TAE treatment could be repeated more times than ADM-Lp-TAE. PMID- 11202799 TI - Patient statement of satisfaction with antiemetic treatment is related to quality of life. AB - The aim of our study was to explore the possible relationship between patient satisfaction with antiemetic treatment and quality of life (QoL). The study sample consisted of 136 chemotherapy-naive patients with breast cancer, with Karnofsky index 90% to 100%, scheduled to receive their first cycle of, mainly adjuvant, 5-fluorouracil/doxorubicin/cyclophosphamide chemotherapy. Two antiemetic regimens were used for the prevention of acute emesis. No antiemetic prophylaxis was given for delayed emesis. QoL was assessed using the Rotterdam Symptom Checklist (RSCL). The RSCL was completed before chemotherapy (day 1) and on day 5. Statement of satisfaction was given on day 5. The change in RSCL scores between day 5 and day 1 was calculated and compared in three subgroups of patients: those very satisfied (n = 55), satisfied (n = 65), and unsatisfied with antiemetic treatment (n = 16). Patient statement of satisfaction was related to psychological distress (p = 0.002), physical symptom distress (p = 0.002), and activity level (p = 0.002). It was also related to the control of nausea (p < 0.01) and vomiting (p < 0.0001). We suggest that patient statement of satisfaction with antiemetic treatment could be an outcome measure for response assessment in antiemetic trials. PMID- 11202798 TI - Pilot study of the paclitaxel, oxaliplatin, and cisplatin combination in patients with advanced/recurrent ovarian cancer. AB - To determine the feasibility of the paclitaxel, oxaliplatin, cisplatin combination in advanced ovarian cancer (AOC), 15 patients with AOC (8 chemonaive, and 7 second-line, disease-free interval > or = 12 months) received paclitaxel 135 mg/m2 at day 1, with oxaliplatin 100 mg/m2 and cisplatin 75 mg/m2 at day 2, every 3 weeks for 6 cycles. Pretreated patients received prophylactic granulocyte colony-stimulating factor (5 microg/kg/d, days 6-13). Seventy cycles were administered; median 5 (range: 2-6 cycles) in chemonaive, and 4 (range: 2-6) in pretreated patients. There were grades III to IV neutropenia in 77%, febrile neutropenia in 24%, and grades III to IV thrombocytopenia in 4% of the cycles. Besides neutropenia, cumulative neurosensory toxicity was also limiting although reversible, with National Cancer Institute Common Toxicity Criteria grades II to III observed in 13 patients. Three of the pretreated patients had complete responses (43%), three had partial responses, and one had disease stabilization. Six of the 8 chemonaive patients had complete responses (75%), 1 had disease stabilization, and 1 had disease progression. The median follow-up is 17 months (range: 9-20 months) in chemonaive and 41 months (range: 13-58 months) in pretreated patients, and time to progression has been consistently more than 12 months, with 6 patients (5 chemonaive) still progression free (range: 15+ to 22+ months). This active combination shows acceptable hematologic toxicity, and reversible cumulative neurosensory toxicity. Further clinical exploration of the present combination appears warranted. PMID- 11202800 TI - Isolated splenic metastasis from gastric carcinoma: value of CEA and CA 19-9 in early diagnosis: report of two cases. AB - We report two cases of an isolated splenic metastasis, occurring 5 and 3 years, respectively, after gastrectomy for gastric carcinoma. Serum carcinoembryonic antigen and CA 19-9 levels were evaluated preoperatively, postoperatively, and during the oncologic follow-up. The patients underwent splenectomy for solitary splenic metastasis. We conclude that the use of serum carcinoembryonic and CA 19 9 values may help in the early diagnosis of these recurrences and splenectomy allows radical treatment in patients with no evidence of disseminated disease. PMID- 11202801 TI - Hepatic angiosarcoma occurring after cyclophosphamide therapy: case report and review of the literature. AB - A 54-year-old man with polyarteritis nodosa developed acute onset of right upper quadrant abdominal pain associated with a large liver mass. Transvenous liver biopsy revealed hepatic angiosarcoma, a rare liver tumor classically associated with environmental toxins. He had been treated with oral cyclophosphamide for 13 years. A review of the literature revealed two other cases of hepatic angiosarcoma in patients after long-term cyclophosphamide treatment. We propose that cyclophosphamide be added to the list of exposures potentially associated with hepatic angiosarcoma. PMID- 11202802 TI - Dose-response relationships for radiotherapy of brain metastases: role of intermediate-dose stereotactic radiosurgery plus whole-brain radiotherapy. AB - The effects of intermediate-dose radiotherapy consisting of whole-brain radiotherapy (WBRT, 10 fractions of 3 Gy) plus stereotactic radiosurgery (SRS) were studied prospectively. Twenty-five adult patients with 31 brain metastases received WBRT plus linear accelerator (LINAC)-based single dose SRS with fixed treatment parameters (10 Gy at the isocenter, target volume enclosed by the 90% isodose). Median age was 63 years, median Karnofsky performance status 80%, and median diameter of brain metastases 2.4 cm. Fifteen patients had non-small-cell lung cancer. Because of some early deaths, only 26 lesions could be evaluated for response. We observed 1 complete and 15 partial remissions. Median time to progression inside or outside the SRS volume was 4.5 months. Actuarial local control of SRS-treated lesions was 61% at 1 year. At that time, only 37% of patients were free from new lesions outside the SRS volume. Median survival and cause-specific survival were 2.3 and 4.5 months, respectively (1-year survival rate 8% and 21%). Ten patients died of progressive brain metastases, 13 from extracranial disease progression (unknown cause of death in 2 cases). Comparable to SRS studies with higher doses, the majority of brain failures occurred outside the SRS volume and more patients died of extracranial progression than of uncontrolled brain metastases. Failure to improve survival can be explained by the high percentage of patients with extracranial metastases (52%). However, the present results appear less favorable than those of previous studies of SRS with 15 Gy to 16 Gy (1-year actuarial local control rates of 66-89%). Therefore, we recommend SRS with 15 Gy to 16 Gy for patients whose favorable prognostic factors justify a boost after WBRT. PMID- 11202803 TI - Phase II pilot study of combined chemohormonal therapy with doxorubicin and estramustine in metastatic prostate cancer. AB - Twenty-nine patients with progressive hormone-refractory metastatic adenocarcinoma of the prostate were treated with daily estramustine phosphate at 10 mg/kg, and I.V. doxorubicin 50 mg/m2 every 3 weeks. Twenty-six patients were evaluable. Four of seven patients with nonosseous measurable disease had partial responses lasting 3 to 10 months. Eleven of 19 patients with osseous metastases had stable disease or improvement on bone scan, 6 of these for 7 months or longer. Median time to progression was 20 weeks, and the median survival was 43 weeks. PMID- 11202804 TI - Reversible renal toxicity resulting from high single doses of the new radiosensitizer gadolinium texaphyrin. AB - Gadolinium (III) texaphyrin (Gd-Tex) (NSC 695238) is a potential radiation sensitizer that selectively localizes in tumors and is detectable by magnetic resonance imaging (MRI). In this single-dose phase I trial, reversible renal injury was the dose-limiting toxicity. This report details that renal injury. A single intravenous dose of Gd-Tex was followed 2 hours later by radiation therapy. The Gd-Tex dose was escalated in 13 patient cohorts. Doses ranged from 0.6 to 29.6 mg/kg. The maximum tolerated dosage (MTD) was 22.3 mg/kg. Three patients had grade II and one had grade III acute nonoliguric renal failure at the 22.3 and 29.6 mg/kg dose levels. The injury was always transient, and responded to fluid restriction and renal diet. In all patients, transient green discoloration including urine developed at doses > or =7.1 mg/kg. MRI studies demonstrated image enhancement in the liver, kidneys, and in primary and metastatic tumors in all patients receiving >5.4 mg/kg. It is important that the liver and kidneys be excluded from the radiation volume. Gd-Tex was well tolerated at doses below the MTD. It is important that the liver and kidneys be excluded from the radiation volume. We recommend that 16.7 mg/kg be used as the maximum single dose to obviate even low grade renal toxicity. PMID- 11202805 TI - Endoscopic findings in chronic lymphocytic leukemia. AB - Retrospective studies, based on autopsy findings, indicate that infiltration of the gastrointestinal tract complicates leukemia of all types and may be present from the esophagus to the rectum. This report presents what is believed to be the first reported case of a patient with chronic lymphocytic leukemia with evidence of esophageal, gastric, duodenal bulb, and colonic involvement confirmed by mucosal biopsy at endoscopy. PMID- 11202807 TI - Tissue polypeptide-specific antigen and carcinoembryonic antigen for early prediction of recurrence in lung adenocarcinoma. AB - Fifty patients with lung adenocarcinoma, including 20 cases with recurrence and 30 cases without recurrence 1 year after operation, were enrolled in this study. The serial serum levels of tissue polypeptide-specific antigen (TPS) and carcinoembryonic antigen (CEA) were measured before operation and at 1 week, and at 1, 3, 6, 9, and 12 months after operation for early detection of recurrence. The results revealed that: 1) mean serum values of TPS were significantly higher at 1, 3, 6, 9, and 12 months after operation in 20 patients with recurrent adenocarcinoma, when compared with 30 patients without recurrent adenocarcinoma; 2) mean serum values of CEA were significantly higher at 9 months and 12 months after operation in 20 patients with recurrent adenocarcinoma, when compared with 30 patients without recurrent adenocarcinoma. We conclude that TPS is a better marker than CEA for early prediction of adenocarcinoma recurrence in lung within 1 year after operation. However, a longer follow-up study should be encouraged. PMID- 11202806 TI - Phase II study of intravenous CI-958 in metastatic colorectal adenocarcinoma. AB - In a multicenter, phase II trial, CI-958, a benzothiopyranoindazole DNA intercalator, was administered to 18 patients who had not received prior chemotherapy for metastatic colorectal cancer. The drug was given by intravenous infusion at a dose of 700 mg/m2 every 21 days. There were no objective responses. Grades III and IV toxic effects were limited to granulocytopenia in 42% of courses and anemia in 5% of courses. There was one case of grade III increase in transaminases. Our results show that at this dose and schedule, CI-958 lacks activity against colorectal cancer. PMID- 11202808 TI - Phase I trial of paclitaxel and etoposide for recurrent ovarian carcinoma: a Gynecologic Oncology Group Study. AB - A phase I study was performed to determine the maximum tolerated doses of intravenous etoposide and paclitaxel for women with previously treated persistent or recurrent ovarian cancer. Starting doses were paclitaxel 135 mg/m2 during 24 hours and etoposide 50 mg/m2/day for 3 consecutive days. The study was designed to escalate first the dose of etoposide, and then the dose of paclitaxel, in successive cohorts of patients. In an attempt to determine whether toxicity was affected by sequence of the drugs, the order of administration of the two drugs was reversed on alternate cycles. The starting doses of paclitaxel (135 mg/m2/24 hours) and etoposide (50 mg/m2/day x 3) caused severe neutropenia even with the addition of granulocyte colony-stimulating factor, and the trial was amended to administer the paclitaxel during 3 hours. However, this also proved too myelosuppressive without growth factor support. Twenty-one women were treated. A complete response was observed in one of nine patients with measurable disease, and a major decrease in CA-125 was noted in two patients who did not have measurable disease. Because of the severe myelosuppression observed in most patients, dose reduction was often required after the first cycle. The power to detect sequence-dependent variation in toxicity was minimal; however, no large differences were observed. A combination of the usual doses of these drugs will be difficult to administer in patients who have received previous chemotherapy for ovarian cancer. PMID- 11202809 TI - Multicentric phase II study of cisplatin and etoposide in patients with metastatic carcinoma of unknown primary. AB - The aim of this study was to determine the efficacy and toxicity of combination cisplatin and etoposide chemotherapy in patients with metastatic carcinoma of unknown primary. Patients were treated with cisplatin (100 mg/m2 iv day 1) followed by etoposide (100 mg/m2 iv days 1-3) every 3 weeks for a maximum of 6 cycles. Patients with progressive disease after two or four courses could receive FAC (fluorouracil, doxorubicin, and cyclophosphamide) until progression. Twenty five patients were entered and were assessable for response and toxicity. Fifteen (60%) patients had adenocarcinomas. Patients received a median of four courses. Toxicity was mainly hematologic including grade III/IV neutropenia. The overall response rate was 32%. There was no complete response, 32% partial responses, 32% stable disease, and 36% disease progression. Median response duration was 4 months (range: 2-5 months). The median overall survival of the 25 patients was 8 months. No objective response could be obtained with FAC, but 33% of patients achieved stabilization of the disease for at least 3 months. This cisplatin etoposide combination demonstrated some activity against an usually resistant disease. PMID- 11202810 TI - Methotrexate, uracil and tegafur, and leucovorin chemotherapy for patients with breast cancer in progression after high-dose chemotherapy with peripheral blood progenitor cell transplant: a phase II study. AB - Thirty-four patients with metastatic breast cancer (MBC) who had progression of disease after high-dose chemotherapy (HDCT) with peripheral blood progenitor cell support (PBPC) had methotrexate, uracil and tegafur (UFT), and leucovorin (MUL) therapy administered: methotrexate administered intramuscularly in combination with UFT given orally and leucovorin given orally. All patients had received extensive prior chemotherapy including a high-dose regimen with PBPC support. Two complete responses (CR) and 11 partial responses (PR) were observed (objective response rate: 13/34 or 38%, 95% confidence interval 22-56%). Seven additional patients had stable disease (SD), 4 of whom (12% of the total population) of 6 months or longer duration, with the clinical benefit rate (CR + PR + SD of at least 6-month duration) reaching 50%. Median follow-up was 38 months, and the median time to progression and the median overall survival time from the start of MUL were 5.5 and 11 months, respectively. Toxicity was mainly gastrointestinal. Eight patients (24%) had World Health Organization grade II or greater diarrhea and/or enteritis and, consequently, the UFT dose was reduced. Emesis was mild and easily manageable with thiethylperazine given orally. The regimen did not produce significant myelosuppression or alopecia. In conclusion, patients with MBC retain chemosensitivity even when they progress after HDCT/PBPC and can be treated again with chemotherapy. MUL is active and well tolerated in patients with MBC progressing after HDCT. Further studies with this regimen, as salvage chemotherapy or as maintenance chemotherapy after HDCT/PBPC, would appear to be warranted. PMID- 11202811 TI - Effect of vinorelbine, ifosfamide, and cisplatin combination chemotherapy in advanced non-small-cell lung cancer. AB - Cisplatin-based chemotherapy is being tried in the treatment of nonoperable cases of non-small-cell lung cancer (NSCLC). However, the prognosis is unfavorable and to improve survival, clinical studies using various combinations of a variety of drugs as well as experimental material are in progress. We compared the efficacy and toxicities of combination chemotherapy using different doses of vinorelbine and ifosfamide with a constant dose of cisplatin in this study. Patients diagnosed with inoperable stage III or IV NSCLC between June 1997 and December 1998 were included. Cisplatin was administered at a constant dose of 80 mg/m2 on day 5, whereas vinorelbine on days 1 and 5 and ifosfamide on day 5 were administered in one of two different doses. In arm A, vinorelbine 25 mg/m2 and ifosfamide 3.0 g/m2 were administered. In arm B, vinorelbine 20 mg/m2 and ifosfamide 2.5 g/m2 were administered. Also, we reviewed for phase II and III studies that test 1) cisplatin, 2) vinorelbine monotherapy, and 3) vinorelbine/cisplatin/ifosfamide combination chemotherapy for stage IIIb-IV non SCLC. Summation dose intensity (SDI) was calculated in each published and current study. Twenty patients in arm A and 35 patients in arm B were available for evaluation. There was no difference in patient activity, pathologic diagnosis, and differentiation or stage between the two arms. The median number of cycles was four in both arms. The response rate was 50% in arm A and 30% in arm B. The median survival times for arm A and B were 40 and 42 weeks, respectively, whereas the SDI was 1.94 and 1.7, respectively. More than grade III leukopenia was observed in 28.9% in arm A, which is more frequent than the 17.2% in arm B. There was a significant correlation between the SDIs and response rates and median survival (r2 = 0.629, p = 0.001; r2 = 0.453, p = 0.001, respectively). Although the follow-up period is relatively short, the survival time was similar in both arms. Because a high response rate may not be followed by a high survival time in combination chemotherapy of NSCLC, further studies on the appropriate dose of individual agents with regard to the relationship between response rate, severity, and incidence of toxicities and survival rate should be carried out. PMID- 11202812 TI - Effects of a single and double commercial athletic mouthpiece on expiratory peak flow: a pilot study. AB - Utilizing an Assess Peak Flow Meter, six healthy subjects with no lung disease volunteered to have their expiratory peak flow measured under the following five conditions: 1. Biting on the oral tube of the peak flow meter and lip-sealing the tube; 2. Using a custom built diaphragm allowing the subject to lip-seal the tube of the peak flow meter without biting on it; 3. Using orange wood blocks of known dimension bilaterally on the posterior occlusion, and a custom built diaphragm allowing the subject to lip-seal the oral tube of the peak flow meter without biting on it; 4. Using a commercial single (maxillary) athletic mouthpiece and a custom built diaphragm allowing the subject to lip-seal the oral tube of the peak flow meter without biting on it; and 5. Using a commercial double (maxillary and mandibular) athletic mouthpiece and a custom built diaphragm allowing the subject to lip-seal the oral tube of the peak flow meter without biting on it. Expiratory peak flow measurements were virtually the same whether the subjects bit and lip sealed on the oral tube of the peak flow meter, used the custom diaphragm and lip sealed without biting on the oral tube of the peak flow meter, or bit on the orange wood blocks while using the custom diaphragm and lip-sealing without biting on the oral tube. There was significant deterioration (p < .0001) in expiratory peak flow volume when either the single or double commercial athletic mouthpieces were employed. PMID- 11202813 TI - The influence of forward head posture on dental occlusion. AB - A well established premise in the field of craniomandibular and cervical spine orthopedics is that forward head posture (FHP) adversely affects mandibular position and therefore dental occlusion. The purpose of this study was to investigate the influence of FHP on the initial occlusal contact pattern (IOCP) in order to provide further clarification on this important topic. Thirty-nine healthy subjects, 10-74 years old, underwent a series of tests in which the IOCP was recorded in four different head positions using the T-Scan Occlusal Diagnostic System. Three tests each were performed in military posture (MP), natural sitting posture (NP), FHP, and maximal forward head posture (MFHP) for a total of twelve trials. A repeated measures analysis of variance failed to demonstrate a correlation between FHP and IOCP; however, a multiple linear regression analysis revealed a relationship between age and the IOCP. This study raises questions about the relationship between FHP and occlusion. PMID- 11202814 TI - Facial pain and temporomandibular disorders: an epidemiological study of the Northern Finland 1966 Birth Cohort. AB - Recent clinical studies have shown an association between temporomandibular disorders (TMD) and facial pain. The aim of this epidemiological study was to investigate the prevalence of facial pain and TMD, their relation to each other, and also their relation to previous traumas, occlusal factors and pain in other areas of the body. The study is a part of the Well-Being and Health Research of the Northern Finland Birth Cohort 1966 using questionnaires where data on facial pain, TMD symptoms, occlusal divergencies, traumas in the face and other pain areas of the body were registered. Data were obtained from 5696 subjects born in the year 1966 in northern Finland. Twelve percent of the men and 18% of the women had suffered from facial pain during the last year. The most often reported symptom of TMD was clicking of the temporomandibular joints (TMJs) (21% in men, 28% in women), while prevalence of more severe symptoms was 13% or under. Facial pain was related to symptoms of TMD, as well as to traumas in the face or TMJs, distal occlusion and other pain areas (neck, shoulders, arms, lower back, jaws, tooth). The results suggest that facial pain is a usual symptom in adult population, and has an association with TMD, as well as with other musculoskeletal pain symptoms. Traumas to face and TMJs, certain occlusal factors and dental pathology may have a remarkable role in the etiology. PMID- 11202815 TI - Rotational and translational loading of the temporomandibular joint. AB - Following an introduction to the functional properties of a three-dimensional instantaneous helical axis pertaining to circular (rotatory) and linear (translatory) motions of the mandible, this feasibility study applied the concept of a mandibular average finite helical axis to the maneuver of cyclic opening and closing of the mouth in three healthy subjects. Through the accelerations and decelerations of a mandibular incisor point (instead of a mandibular condylar point) as well as the laws of physics, the kinetic reaction forces and reaction pressures in the upper and lower cavities of the temporomandibular joint (TMJ) were estimated over opening-closing distances of five and ten mm from centric occlusion. The translatory reaction pressures in the upper TMJ cavity (17-29 mm Hg) exceeded the rotatory reaction pressures in the lower TMJ cavity (5-12 mm Hg). The estimated reaction pressures were in close agreement with synovial fluid pressures measured in vivo in the TMJ of humans and pigs, and the biologic significance of frequent and/or prolonged increased TMJ hydrostatic pressures is discussed. PMID- 11202816 TI - Is NIH capable of changing the lifestyle of all TMD patients? PMID- 11202818 TI - Arthrogryposis multiplex congenita in a patient with limited mouth opening: a case report. AB - This report describes a case of arthrogryposis multiplex congenita and concomitant bruxism with limited mouth opening and pain in the temporomandibular joints (TMJ). A conservative treatment with a myorelaxing splint and physiotherapeutic exercises was prescribed resulting in improvement to the muscular and joint conditions and a reduction in pain. PMID- 11202817 TI - Better palpation of pain: reliability and validity of a new pressure pain protocol in TMD. AB - The purpose of this research was to employ a double-blind placebo control design of iontophoretically administered lidocaine to assess the test-retest reliability and validity of a magnitude matching procedure using a pressure algometer. In studies in the literature on assessment of pain in temporomandibular disorders (TMD), the pressure algometer has been found to be a reliable means of measuring pressure-pain threshold and a sensitive measure of treatment-response in the laboratory. However, previous research with this apparatus has not employed more sophisticated psychophysics. This study employs a magnitude matching psychophysical protocol to obtain a multidimensional pain report. Test-retest reliability over two occasions, 3-8 days apart, was found to be moderate for discriminability (r = .71, p < .01) but poor for response bias (r = .44). The validity study used iontophoresis as an anesthetic in a double-blind placebo and no-treatment control design. Although it was hypothesized that subjects in the anesthesia group would demonstrate reduced discriminability as compared with the control groups, no differences were found among the three groups on this measure. However, differences in response bias were found, with both the placebo control and no-treatment control groups differing from the experimental group but not from each other. Possible explanations and the implications of these findings are discussed. PMID- 11202819 TI - Temporomandibular disorder treatment outcomes: first report of a large-scale prospective clinical study. AB - The diagnosis and treatment of temporomandibular disorders (TMD) has been surrounded by considerable controversy. Clinical research in the field to date has been inconsistent and methodologically limited and has not firmly established the role of treatment interventions. This large scale, multisite study attempts to answer some of the questions regarding TMD diagnosis and treatment. More than 6,500 patients are currently being analyzed and 1,212 have completed TMD therapy, providing the basis for comparison with 198 untreated patients. A wide variety of treatments have been administered from 60 practice sites, whose practitioners were carefully calibrated to maximize inter-rater reliability. A validated symptom measurement system, the TMJ Scale, was employed to assure uniform assessment of treatment outcomes. Treated patients reported statistically and clinically significant symptom improvement, while untreated patients reported unchanged symptom levels. Data presented here do not support the hypothesis that TMD patients improve spontaneously without treatment. PMID- 11202820 TI - Relationship between craniomandibular disorders and poor posture. AB - The purpose of this research was to show that a relationship between craniomandibular disorders (CMD) and postural abnormalities has been repeatedly postulated, but still remains unproven. This study was intended to test this hypothesis. Twenty-five CMD patients (mean age 28.2 years) were compared with 25 gender and age matched controls (mean age 28.3 years) in a controlled, investigator-blinded trial. Twelve postural and ten muscle function parameters were examined. Measurements were separated into three subgroups, consisting of those variables associated with the cervical region, the trunk in the frontal plane, and the trunk in the sagittal plane. Within these subgroups, there was significantly more dysfunction in the patients, compared to control subjects (Mann-Whitney U test p < 0.001, p < 0.05, p < 0.01). Postural and muscle function abnormalities appeared to be more common in the CMD group. Since there is evidence of the mutual influence of posture and the craniomandibular system, control of body posture in CMD patients is recommended, especially if they do not respond to splint therapy. Whether poor posture is the reason or the result of CMD cannot be distinguished by the data presented here. PMID- 11202821 TI - Prolonged mandibular hypomobility patient with a "square mandible" configuration with coronoid process and angle hyperplasia. AB - The objective of this study was the surgical management of chronic severe mandibular hypomobility patients associated with square mandible morphology with coronoid process and angle hyperplasia, and one-year follow-up data is reported. Ten patients were studied. All patients were female and had a history of gradual severe jaw hypomobility. Clinical findings were similar to those of a "closed lock" patient. However, the facial appearance in these patients showed a characteristic square mandible facial configuration. Coronoid process thickening and overgrowth of the mandibular angle was evident in the radiographic findings. Diagnostic imaging scarcely depicted any disk derangement, but a severely limited jaw opening was noted in spite of acceptable excursive jaw movements. Bilateral coronoidotomy or coronoidectomy was done initially, and then masseter muscle stripping via the intraoral approach. After successful reduction of jaw hypomobility, a selective mandibular anglectomy was completed. Physical therapy began within three to five days after the surgery. Postoperatively, all patients were questioned about their jaw function and their subjective assessment of the treatment. Interincisal jaw opening was recorded with a ruler marked in millimeters. Bilateral coronoidotomy or coronoidectomy and masseter muscle stripping were done for all patients; the mandibular anglectomy was performed in seven of the cases at 13 sites. Simultaneous TMJ surgery was done on three joints for three patients. Most patients reported improvement of jaw function, and the patients' subjective assessment revealed an average satisfaction rate of 74.6%. A preoperative mean jaw opening distance of 25.6 mm increased to 36.6 mm postoperatively at a one-year follow-up (p < 0.05). The conclusion was that surgical intervention is indicated when nonsurgical treatment is unsuccessful. Etiology is unknown, but masseter and temporal muscle contracture associated with mandibular coronoid and angle hyperplasia may be a strong component of the pathophysiology. PMID- 11202822 TI - The effect of surgical treatment of the temporomandibular joint: a survey of 70 patients. AB - Most patients with temporomandibular disorders (TMD) can be successfully treated by conservative methods, but approximately 10-20 percent have persistent symptoms. The aim of this study was to evaluate the signs and symptoms of TMD in patients treated with open surgery of the TMJ. Seventy-two patients (13 men, 59 women, mean age 37 years, range 14-68 years) were evaluated during an eight-year period. Altogether 45 right TMJs and 39 left TMJs were treated, including both TMJs during the same operation in eight of the cases. The patients were evaluated at follow-up in 1997. The degree of TMD at follow-up was assessed using the anamnestic and clinical dysfunction Helkimo indices. Most of the patients reported at the follow-up that they were subjectively satisfied with the surgical treatment. The main clinical findings in the post surgical patients at follow-up were TMJ sounds and deviation of the mandible during opening. The tenderness in the masticatory muscles and TMJs on palpation was reduced significantly and the ranges of mandibular movement were improved for all the patients. The mean anamnestic and clinical indices decreased with a statistical significance from the shortest follow-up group (Group I) to the longest on group (Group IV) (p = 0.000). The conclusion of this study was that after open surgical treatment of the TMJ, the patients have significantly better functioning of the masticatory system and reduced signs and symptoms of TMD in the long term. PMID- 11202823 TI - Relationship between dental occlusion and posture. AB - The purpose of this study is to show the effects of dental occlusion on postural position. Thirty subjects were divided into two groups: an experimental group who wore mandibular orthopedic repositioning appliances (MORA) and a control group who wore no oral device. All of the subjects underwent the same Fukuda Unterberger experimental stepping test to check their postural attitude. Any deviation of the subject during the test from his initial position was analyzed. The results seemed to confirm that altering dental occlusion by wearing an oral appliance could induce some fluctuations in dynamic postural attitude. The phenomenon occurs after prolonged wearing of a MORA. Feedback effects are gradual after removing the mandibular splint. PMID- 11202824 TI - The effects of collagen hydrolysat on symptoms of chronic fibromyalgia and temporomandibular joint pain. AB - Twenty (20) people who had medically diagnosed fibromyalgia for two to 15+ years participated in and completed a 90-day evaluation to determine effects of collagen hydrolysat on symptoms of chronic fibromyalgia, with twelve reporting temporomandibular joint pain. Collagen hydrolysat is a food supplement that is available without prescription, with no known side effects. Participants were evaluated initially and then at 30-, 60-, and 90-day periods. Final results were obtained and comparisons made. The average pain complaint levels decreased significantly in an overall group average, and dramatically with some individuals. It was concluded that patients with fibromyalgia and concurrent temporomandibular joint problems may gain symptomatic improvement in their chronic symptoms by taking collagen hydrolysat. PMID- 11202825 TI - A study of dentists' knowledge and beliefs regarding temporomandibular disorders in Korea. AB - The purpose of this study was to examine the knowledge and beliefs regarding TMD (temporomandibular disorders) held by practicing dentists in Seoul, the capital and largest city in Korea. Four aspects of TMD (psychophysiological, psychiatric disorders, chronic pain and pathophysiological) were examined. The results indicate that while the role of psychophysiologic factors in the etiology of TMD and the role of psychiatric disorders is relatively widely acknowledged in the practicing community, there is a high level of controversy regarding the pathophysiology of TMD and the appropriate diagnosis and treatment of these chronic conditions. The findings partially duplicate a similar survey of dentists in Seattle, Washington, and one survey done in Kansas in the United States. PMID- 11202826 TI - Orofacial pain specialty opposition. A call to "de-fragment". PMID- 11202827 TI - In response to John Radke's January 2000 editorial. Dr. Gottlieb says, "beware of the obvious.". PMID- 11202828 TI - Surface electromyographic evaluation of the asymptomatic human masseter muscle with turns and amplitude analysis. AB - Electromyographic turns, or reversals of direction, per second (TS) and mean amplitude per turn (AT) are variables that have been widely used to assist and support an electrodiagnosis in neuromuscular disorders. The purpose of this study was to explore the feasibility of utilizing the TS and AT in conjunction with surface electrodes as a method for assessing masticatory muscle function. Ten normal subjects were instructed to exert brief isometric contractions at various levels, and the TS and AT were calculated from the surface electromyographic signals of the masseter muscle. Our results showed that the AT increased with contraction at all contraction levels, demonstrating a linear relationship, while the TS showed a nonlinear increase characterized by an initial steep rise followed by a plateau, which was simulated with a third polynomial function. It is considered that the TS and AT may provide valuable physiological information about the underlying mechanisms of recruitment and the firing of motor units. PMID- 11202829 TI - Prevalence and patterns of nocturnal bruxofacets on stabilization splints in temporomandibular disorder patients. AB - The purpose of this study was to investigate the prevalence of nocturnal bruxism, the characteristics of bruxofacets, and the reduction of symptoms in temporomandibular disorder (TMD) patients. The study involved the observation of bruxofacets on a stabilization splint. Twenty-six patients (22 women and 4 men, 16-54 years of age) with signs and symptoms of TMD were given an initial examination before using a splint, and then at intervals of one, three, six and ten weeks after a stabilization splint was first used. In 88% of the patients (n = 23) active shiny facets or scratches caused by nocturnal bruxism appeared on the occlusal surface of splints within ten weeks. In 52% of the 23 patients these facets were created by bilateral mandibular excursions, in 35% by small lateral movements, and in 13% by unilateral excursions. Subjective pain and the Craniomandibular Index in patients had decreased after ten weeks (p < 0.001), but a reduction of symptoms did not differ according to the patterns of the bruxofacets. It was concluded that most TMD patients have a parafunctional habit, namely bruxism. Further research is needed to produce more convincing evidence of a true cause-and-effect relationship between nocturnal bruxism and TMD. PMID- 11202830 TI - Effects of a mandibular advancement device for the treatment of sleep apnea syndrome and snoring on respiratory function and sleep quality. AB - In this study the fabrication of a simplified mandibular advancement device for sleep apnea syndrome was described. Its effect on respiratory function and sleep quality variables was evaluated polysomnographically in 256 patients with sleep apnea syndrome and snoring. Polysomnographic recordings were performed twice, before and after insertion of the oral appliance. The mean apneahypopnea index (AHI) decreased significantly (p < 0.0001) with the appliance to 18.2 from 43.2 without it. Responders defined by AHI < 10 were 54% and those defined as a 50% decrease of AHI were 66%. Oxygen saturation, duration of apnea, sleep efficiency, and total arousal were improved significantly after treatment without major side effects. The device improved significantly the respiratory function and sleep quality in patients with sleep apnea syndrome. Compliance was about 90% followed for 2.5 years. This appliance offers some advantages over other therapies because it is noninvasive, easy to fabricate, and well accepted by patients. PMID- 11202831 TI - A difficult path to walk. PMID- 11202832 TI - Another voice is heard in support of rejecting specialty status for orofacial pain. PMID- 11202833 TI - The craniocervical connection: a retrospective analysis of 300 whiplash patients with cervical and temporomandibular disorders. AB - Because the concept of whiplash as a causative factor for temporomandibular disorders (TMD) is highly controversial, we decided to do a retrospective analysis of patients treated in our office who had sustained whiplash injuries and were treated for cervical and temporomandibular disorders. The records of 300 patients with TMD preceded by a motor vehicle accident were examined retrospectively. The most common presenting symptoms, in order, were: jaw pain, neck pain, post-traumatic headache, jaw fatigue, and severe temporomandibular joint (TMJ) clicking. The most common TMD diagnoses were: masseter trigger points, closing jaw muscle hyperactivity, TMJ synovitis, opening jaw muscle hyperactivity, and advanced TMJ disk derangement. Based primarily on the physical examination, we concluded that the TMJ and surrounding musculature should be examined similarly to other joints, with no preconceived notion that TMD pathology after whiplash is unlikely. PMID- 11202834 TI - An alternate technique for management of acute closed locks. AB - The article introduces an alternative method for manipulation and reduction of acute closed locks. The method is described as the Assisted Lateral Reduction Technique (ALRT). The authors have used the ALRT on more than 150 patients and found it more effective and easier to administer than the more common manipulation and reduction techniques (MRT) in the management of acute closed locks which have been extensively documented in the literature. Both techniques are highlighted, compared, and discussed in the article. PMID- 11202835 TI - Orofacial sensory changes and temporomandibular dysfunction. AB - Orofacial sensory changes are uncommon complaints that can coexist with temporomandibular dysfunction (TMD). The location, character, and intensity vary greatly with each individual and symptom fluctuation is not unusual for any patient. The etiology of orofacial sensory changes may be related to either local or systemic factors. Several investigators have reported that muscle entrapment of branches of the third division of the trigeminal nerve may result in orofacial sensory disruption. Different theories have been suggested to illustrate how TMD and trauma might be associated with these neurological changes. Additionally, several mechanisms exist to explain how muscle spasms may be responsible for nerve compression in individuals with normal anatomy and in those with anatomical variations. In this study, thirty subjects from a group of 282 TMD patients were found to have coexisting orofacial sensory disturbances and TMD. Subjects presenting with any neurological complaints should alert the clinician to the possibility that these symptoms may be the early clinical signs of serious disease. PMID- 11202836 TI - Effects of head and neck inclination on bilateral sternocleidomastoid EMG activity in healthy subjects and in patients with myogenic cranio-cervical mandibular dysfunction. AB - This study was conducted in order to determine the effect of head and neck position on bilateral electromyographic (EMG) activity of the sternocleidomastoid muscles. The study was performed on 16 patients with myogenic cranio-cervical mandibular dysfunction (CMD) and 16 healthy subjects. EMG recordings at rest and during swallowing of saliva and maximal voluntary clenching were performed by placing surface electrodes on the right and left sternocleidomastoid muscles. EMG activity was recorded in the left lateral decubitus position, in a darkened room and with the individual's eyes closed, under the following experimental conditions: 1. Head, neck, and body horizontally aligned; 2. Head and neck upwardly inclined with respect to the body, simulating the effect of a thick pillow, 3. Head and neck downwardly inclined with respect to the body, simulating the effect of a thin pillow. Variation of head and neck positions was determined by measuring the distance from the angle of neck and shoulder and the apex of the shoulder (SND = shoulder-neck distance) of each individual. Then, head and neck were forward or downwardly inclined with respect to the body at one-third of SND. A significantly higher contralateral EMG activity and a more asymmetric EMG activity were observed in the CMD group than in the healthy subjects (Kruskal Wallis Test). These results suggest a different behavior of bilateral sternocleidomastoid EMG activity in CMD patients than in healthy subjects depending on the positioning of the head and neck. PMID- 11202837 TI - Relationship between systemic joint laxity, TMJ hypertranslation, and intra articular disorders. AB - The aim of this study was to evaluate the correlation between general joint hypermobility, temporomandibular joint (TMJ) hypertranslation and signs and symptoms of TMJ intra-articular disorders. One hundred twenty individuals constituted the sample, divided into two groups: Group I (symptomatic) included 60 patients with complaints of joint noises, pain, or jaw locking, and Group II (nonsymptomatic) included 60 people with no TMD complaints. The Beighton's hypermobility score addressed the systemic laxity while lateral x-rays taken in both closed and full open mouth positions measured TMJ mobility (condyle hypertranslation). No association was found between intra-articular disorders and systemic hypermobility (p > 0.05). A significant negative correlation (p < 0.05) was found between age and systemic hypermobility, while no correlation was detected between systemic and TMJ hypermobility (condyle hypertranslation). PMID- 11202838 TI - Effect of parafunctional clenching on temporomandibular disorder pain and proprioceptive awareness. AB - This study tested the hypothesis that parafunctional clenching increases pain, can lead to a diagnosis of temporomandibular disorder (TMD) pain, and can produce reductions in proprioceptive awareness. Twenty individuals participated in EMG biofeedback training sessions on the left and right temporalis and masseter muscles. No subjects had TMD prior to training. Subjects were randomly assigned to either a Decrease group, who were instructed to maintain EMG activity below 2 microV during training, or an increase group, who were instructed to maintain EMG activity above 10 microV. To test the impact of parafunctional clenching on proprioceptive awareness, all subjects were instructed to barely touch their teeth together while EMG activity was recorded pre- and post-training. Three subjects assigned to the Increase group and no subjects assigned to the Decrease group were diagnosed with TMD pain following training. Self-reported pain post training was significantly higher for the Increase group. Parafunctional clenching did not affect performance in the proprioceptive test. PMID- 11202839 TI - Profile of TMD and Bruxer compared to TMD and nonbruxer patients regarding chief complaint, previous consultations, modes of therapy, and chronicity. AB - This comparative study by groups assesses the profiles of TMD (temporomandibular dysfunction) and bruxism patients and TMD-nonbruxing patients regarding chief complaint, previous medical and dental consultations, duration of the chief complaint, previous medication, and use of splints. The sample consisted of a group of 340 TMD patients, 275 of whom were bruxers and 65 who were nonbruxers. Both patients and controls were consecutive referrals over a period of five years. The group of TMD and Bruxer was classified according to the degree of severity. One hundred eight (108), 84, and 83 patients demonstrated mild, moderate, and severe bruxism respectively. Information gathered included a set of questionnaires, history of signs and symptoms, and a clinical examination. The most common chief complaints in TMD bruxers and nonbruxers were facial, temporomandibular joint, headache and/or cervical pain, and joint noises. It was observed that the need for medical and dental consultations increased with the severity of bruxism. It was also apparent in this study that the need for medication (analgesics, muscle relaxants, and antidepressants), increased with the severity of bruxism. Moderate and severe subgroups of bruxers used significantly more splints compared to mild bruxers and to TMD-nonbruxer patients. Both groups of TMD + bruxism and TMD - nonbruxism sought medical and dental consultations with dentists (clinicians and specialists) neurologists, and otolaryngologists more frequently compared to other medical professionals. Since the need for health services increased with the severity of bruxism, this study urges the need to include a protocol or questionnaire to assess the severity of bruxing behavior in TMD patients in order to use a customized method of treatment/management. This study also reinforces the point of view that different subgroups of TMD and bruxism do exist and suggests a differentiated therapeutic approach. They show previously confirmed findings that pain is the major complaint of TMD and bruxer patients. PMID- 11202841 TI - NYSTAR, New York's new organization to fund and promote academic research for the marketplace. PMID- 11202840 TI - Evaluation of the slope of the articular eminence and the transverse angle of the glenoid fossa in an Anatolian population. AB - The purpose of this study was to compare a computer-aided method specially programmed for the measurement of the posterior angle of the articular eminence with formerly used methods, to investigate the angulation differences at different depths of slices, and to evaluate correlation with the transverse angulation. Three slices (central, medial, and lateral) at various depths of the glenoid fossa belonging to 64 dry skulls and two measurement methods were used in this study. The angulation of the articular eminence were measured and the transverse angle of each fossa calculated. No statistical difference was found between the articular eminence results of the two methods. According to the results, the one factor ANOVA central slice was found to be statistically steeper than the other two slices (p < 0.05) (central = 60.33 +/- 10.19, medial = 58.26 +/- 8.6, lateral 58.28 +/- 10.1). No correlation was found between the transverse angle of the inclination of the posterior slope angulation. It was concluded that the computer-aided method is more reliable and accurate and is much easier to use when compared to the manual method. An additional important finding of this study is that the inclination of the articular eminence should be evaluated at various depths of the temporomandibular joint. PMID- 11202842 TI - Dr. Friedman comments on Suarez article in the July issue of CRANIO in which he is cited as a reference. PMID- 11202843 TI - The trigeminal nerve. Part I: An over-view. AB - The trigeminal nerve is the largest and most complex of twelve cranial nerves. Its vast size and influence are greatly appreciated when one attempts to diagnose and treat patients suffering from orofacial pain and temporomandibular joint disorders. Without a thorough knowledge of the trigeminal nerve, the efficacy of diagnostic and therapeutic procedures will be very disappointing. This is the first of a four-part series of articles about the trigeminal nerve, a basic over view of both the gross and neuroanatomical structures is presented. PMID- 11202844 TI - The McGill Pain Questionnaire in patients with TMJ pain and with facial pain as a somatoform disorder. AB - The purpose of this study was to assess the discriminative capacity of the McGill Pain Questionnaire (MPQ) in patients with temporomandibular joint disorders (TMD) or with facial pain disorder as somatoform disorder (referred to as "atypical facial pain") (FP). The MPQ was administered to 57 TMD and 34 FP patients. Weighted MPQ item scores, subscale Pain Rating Indexes (PRI), and total Pain Rating Index were tested for significant differences (Student's t-test), and the frequency of descriptor choice was also analyzed. Furthermore, the data were processed through two systems based on a counter-propagation neural network: the Self-Organizing Map (SOM) system and a cluster-like analysis. In the FP group eleven MPQ item scores and five PRI scores were significantly higher than those of the TMJ group. There was a considerable difference in descriptor choice between the groups. SOM analysis and cluster-like analysis correctly discriminated 85% or more of the patients. In conclusion, the MPQ showed a consistent discriminative capacity between TMD and FP patients. PMID- 11202845 TI - Asymmetry of masticatory muscle activity during the closing phase of mastication. AB - The purpose of this study was to investigate the asymmetry of masticatory muscle activity between working and nonworking sides in the closing phase during mastication. Fifty adult subjects displaying normal oral function and occlusion participated in this study. Electromyographic (EMG) activity of the anterior temporalis and the superficial masseter muscle were recorded during mastication, simultaneously with motion data of the mandible. EMG activities of elevator muscles and their Asymmetry Index (AI) were analyzed depending on the vertical deviation of the lower incisal point with a two mm gap from the intercuspal position (ICP). EMG activities of both the anterior temporalis and the masseter on the working side were significantly greater than those on the nonworking side. Masseter muscles tended to show greater AI than the anterior temporalis muscles. Thus, asymmetry of the elevator muscles during mastication was a common finding in normal subjects. The normal range of variability of EMG activity and AI was confirmed in each section. PMID- 11202846 TI - Comparison of the effectiveness of arthrocentesis in acute and chronic closed lock: analysis of clinical and arthroscopic findings. AB - The objective of this study was to investigate the effectiveness of temporomandibular joint arthrocentesis in acute and chronic closed lock patients. Eighteen patients with closed lock of the temporomandibular joint (TMJ) were treated with fine needle fiber arthroscopic observation following arthrocentesis. Maximal mouth opening (MMO) and intensity of pain (VAS) were evaluated at pretreatment and each posttreatment appointment (one week, one month, three months following treatment). The clinical and arthroscopic findings were analyzed categorizing two groups into: good (A) and poor (B) groups. At pretreatment there was no significance relative to age or the mean MMO and VAS between the groups, but the mean of duration of the symptoms in group B was significantly longer than in group A (P < 0.03). Group B showed more severe synovitis, adhesions, and chondromalacia than group A (P < 0.01). Results suggest that arthrocentesis is more effective in closed lock of short duration where there is less severe synovitis, adhesions, and chondromalacia. PMID- 11202847 TI - Joint vibration analysis in patients with articular inflammation. AB - The study of articular sounds using a computerized system (SonoPAK) in patients with temporomandibular disorders (TMD) of inflammatory origin revealed an increase of vibratory energy when compared to asymptomatic individuals. The following conclusions were reached: 1. The amount of vibratory energy registered in these patients ranged from 8.50 to 57.61 Hz. The major vibrations occurred in the middle of the mandibular opening cycle; 2. The mean vibratory energy measured at less than 300 Hz was between 5.70 and 48.64 Hz and at higher than 300 Hz was between 3.70 and 8.99 Hz; 3. The peak amplitude in the patients with inflammation ranged from 0.35 to 3.96 Pascal and the peak of frequency from 83.20 to 120.20 Hz. PMID- 11202848 TI - Different effects of nocturnal parafunction on the masticatory system: the Weak Link Theory. AB - It is proposed that damage to the masticatory system from intense parafunction can be assessed more accurately by the Weak Link Theory. The theory predicts that the more intense and the more prolonged the forces, the more the tendency of damage to either. 1. the periodontal tissue; 2. the teeth; or 3. the orofacial structures. To test the theory, 22 subjects were selected based on reports of nocturnal bruxism. Each was assessed for masticatory system breakdown on the Russell Periodontal Index, the Helkimo Dysfunction Index, and a Tooth Wear Index. A Bruxcore (Forgione, A. 1974 J Dent Res 53:127) was used to obtain an objective score of bruxism. Five of eleven subjects with mild bruxism scored high on only one index. Significantly more subjects (ten of eleven) with moderate to severe bruxism scored high on one index only. PMID- 11202849 TI - Synovial chondromatosis of the left temporomandibular joint superficially resembling chondrosarcoma: a case report. AB - A 25 year-old woman was referred to the clinic complaining of pain in the left temporomandibular joint (TMJ) and trismus. According to the x-ray images, a solitary mass was observed in the anterior pouch of the lower joint cavity. The mass was removed by means of a synovectomy and a diskectomy. Upon light microscopic examination, the tissue removed showed high cellular activity. As a differential diagnosis, we had to consider the possibility of chondrosarcoma based on the histopathological features; however, since no invasive nor metastatic finding was recognized, we made a diagnosis of synovial chondromatosis despite its rare existence. Although there has been no sign of recurrence at present, we plan to carefully follow up with the patient. PMID- 11202850 TI - Macrophages in periapical lesions. AB - Macrophages are major constituents of periapical granulomas. They have a central protective role in both innate immunity and adoptive, antigen-specific immune response. Macrophage activation may occur in periapical granulomas by cytokines produced by antigen-activated T-lymphocytes; by bacterial endotoxin, as part of the innate immunity; or by both these processes. Recent studies in athymic animals have shown that periapical granulomas may develop independently of T lymphocytes. This observation reveals the major role that the activated macrophage may have in the formation of periapical lesions. Only a few of the macrophages in the periapical granuloma are activated. Current studies indicate that these activated cells are the source of the bone-resorbing cytokines in the periapical granuloma. Understanding the central role of the activated macrophage in the formation as well as the perpetuation of periapical lesions may lead to the development of new diagnostic and therapeutic tools in endodontics. PMID- 11202851 TI - Direct and indirect time spent on care of dental trauma: a 2-year prospective study of children and adolescents. AB - The aim was to account for the total time spent by professional care-givers (direct time) and by patients and companions engaged as support and help (indirect time) to treat and otherwise attend to children and adolescents with dental trauma to primary and permanent teeth. The study was based on a random sample of 192 children and adolescents with dental traumas reported to an insurance company and prospectively followed up by telephone interviews over a period of 2 years after the trauma episode. On average, direct time represented 16% of total time for all visits for dental trauma to permanent teeth and 11% for trauma to primary teeth. The most extensive type of indirect time was transport time, which took up 30% of the total time spent on injuries to permanent teeth and 36% for injuries to primary teeth. Multiple regression analysis of the impact of dental and demographic injury variables on the time variables showed that complicated trauma was associated with extended time, direct as well as indirect, for permanent and primary teeth injuries. Our estimate of the average relative increase in total time spent by patients and companions in cases of complicated injury to permanent teeth was 117% (95% confidence interval [CI], 52-211) for patients and 112% (95% CI, 42-217) for companions. For transport time a strong predictor was access to a dental clinic near the place of residence. Lack of access could extend the average transport time by 180% (95% CI, 80-335) for patients and 163% (95% CI, 67-317) for their companions in cases of injuries to primary teeth. PMID- 11202852 TI - Diagnosis of external root resorption using TACT (tuned-aperture computed tomography). AB - This study compared the ability of the TACT system of imaging and conventional D speed film to detect simulated resorptive defects in cadaver teeth and jaws. Mandibular human jaw blocks were prepared and then split through the teeth in a mesial to distal direction so that the mandibular halves could be opened and reassembled when necessary. One half of each of 42 teeth was extracted, and areas on the tooth and corresponding bone identified to be studied. The jaws were opened and reassembled after no defects or after defects of different sizes (0.25, 0.5, 1.0, 2.0 mm) were placed in the tooth and the corresponding bone at predetermined evaluation areas. The teeth were imaged after each stage with conventional D-speed film using a standard paralleling technique, and with a modified orthopantomograph OP100 machine using a Schick #2 size CCD sensor as the image receptor. The source images were registered and TACT slices were generated using TACT Workbench Software. Three observers were asked to identify the presence of resorptive defects in the conventional film group and the TACT image group using specific criteria. TACT imaging was statistically superior to conventional radiographs in detecting defects that were present (Wilcoxon matched pairs signed ranks test P = 0.003). This was true for all sizes of defects examined. There was no difference between the two modalities when a defect was not present. PMID- 11202853 TI - Leakage along warm gutta-percha fillings in the apical canals of curved roots. AB - The aim of this study was to investigate the leakage along the apical portion of warm gutta-percha obturated curved canals. Human mandibular premolars with single, curved (21 degrees-40 degrees) canals were prepared using the Lightspeed technique. Two groups of prepared canals, matched according to curvature and prevalence of apical transportation, were obturated by two techniques. Coronal gutta-percha was removed immediately after root obturation was completed to simulate the procedure for post space preparation. Leakage along the apical 3 mm of root filling was measured with a fluid transport device. Vertical condensation of warm gutta-percha and Pulp Canal Sealer provided less leakage than Thermafil plastic obturators and AH26 sealer (P = 0.002). PMID- 11202854 TI - An analysis of 58 traumatically intruded and surgically extruded permanent teeth. AB - Fifty-eight traumatically intruded and mainly surgically extruded permanent teeth were followed up for 3 years and 4 months (mid-term results: 29 teeth) and 9 months (short-term results: 29 teeth) on average. Statistically, the mid-term results showed more cases of severe crown discoloration (54%) than the short-term results (9%), but no difference in pulpal and periodontal healing. Three teeth (5%) were lost. Factors which positively influenced pulpal healing were shallow intrusion depth, intact crown and immaturity of the root. Factors which positively influenced periodontal healing were shallow intrusion depth and minimal surgical manipulation. Alveolar bone healing was positively influenced only by shallow intrusion depth. PMID- 11202855 TI - Evaluation of a computer-assisted learning package on the management of traumatised incisors by general dental practitioners. AB - A computer-assisted learning program with a tutorial, self-assessment exercises and an expert system has been developed. Sixty-seven general dental practitioners were requested to evaluate the program. The results from those practitioners who returned the questionnaire showed that 57% found the program generally easy to use with the appropriate level of difficulty of tasks and content of supporting information, which it was felt improved their knowledge of the management of fractured incisors. CONCLUSION: It is worthwhile to develop such programs for the education of general dental practitioners. All users of this program felt that it was better than video, audio tapes, journals or books on the subject. PMID- 11202856 TI - Multiple fractures of primary molars caused by injuries to the chin: report of two cases. AB - Two cases of multiple fractures of the primary molars caused by injuries to the chin are presented. Clinical and radiographic examinations revealed a vertical fracture line in the maxillary and mandibular primary molars. Pulpotomy or pulpectomy treatment was performed on the affected teeth, which were then restored with preformed stainless steel crowns. PMID- 11202857 TI - Hypothermic insult to the periodontium: a model for the study of aseptic tooth resorption. AB - The aim of the current investigation was to define an animal model for the study of hard tissue resorption by examining the responses of the periodontal ligament (PDL) to both single and multiple episodes of hypothermic injury to the crowns of rat teeth. A group of 12 male rats weighing 200-250 g were anesthetized, and pellets of dry ice (CO2) were applied once to the crowns of the right first maxillary molars for continuous periods of 10 or 20 min. Animals were sacrificed at 2, 7, 14 and 28 days and tissues were processed for routine histological examination. A second group of eight animals and a third group of 12 animals were subjected to three applications of dry ice over a period of 1 week and sacrificed at 2 and 14 days respectively after the final application. In addition to thermal insult, the periodontium of teeth from a fourth group of six rats was subjected to mechanical trauma. Examination of the sections from the group undergoing a single freezing episode revealed that, by 1 week, shallow resorption lacunae had appeared on the root surface. These became more extensive after 14 days. At the same time hyaline degeneration was evident in the PDL. Within this group, teeth subjected to the longer 20-min application times generally showed more extensive injuries. By 28 days, evidence of repair was observed with reparative cementum beginning to line the resorption lacunae in the root dentin. Sections from animals subjected to multiple episodes of thermal trauma and those subjected to additional mechanical insult showed more extensive external root resorption than those from single-injury animals. It was concluded that low temperature stimuli applied to the crowns of rat molars were capable of eliciting a sterile degenerative response in the PDL which, in turn, resulted in external root resorption. Furthermore, the degree of this tissue injury was commensurate with the duration and number of exposures to the trauma. The results also indicated that progression of the resorptive process required periodic exposure to the injury, in the absence of which repair to the damaged root occurred. PMID- 11202858 TI - Microsurgical instruments for root-end cavity preparation following apicoectomy: a literature review. AB - Root-end cavities have traditionally been prepared by means of small round or inverted cone burs in a micro-handpiece. Since sonically or ultrasonically driven microsurgical retrotips became commercially available in the early 1990s, this new technique of retrograde root canal instrumentation has been established as an essential adjunct in periradicular surgery. At first glance, the most relevant clinical advantages are the enhanced access to root ends in limited working space and the smaller osteotomy required for surgical access because of the various angled designs and small size of the retrotips. However, a number of experimental studies comparing root-end preparations made with microsurgical tips to those made with burs have demonstrated other advantages of this new technique, such as deeper cavities that follow the original path of the root canal more closely. The more centered root-end preparation also lessens the risk of lateral perforation. In addition, the geometry of the retrotip design does not require a beveled root end resection for surgical access thus decreasing the number of exposed dentinal tubules. A controversial issue of sonic or ultrasonic root-end preparation is the formation of cracks or microfractures, and its implication on healing success. The present paper reviews experimental and clinical studies about the use of microsurgical retrotips in periradicular surgery and discusses many issues raised in previous papers. PMID- 11202859 TI - In vitro viability, mitogenicity and clonogenic capacity of periodontal ligament cells after storage in four media at room temperature. AB - The choice of storage medium for preserving traumatically avulsed teeth is important for the success of future replantation. The objective of this study was to compare the effectiveness of four recommended storage media (Hank's balanced salt solution [HBSS], culture medium, alpha minimal essential medium [alpha-MEM], and ViaSpan) to preserve cultured periodontal ligament fibroblasts (PDLF) at room temperature (22 degrees C). PDLF were obtained from explants of extracted healthy human teeth. Plates with confluent PDLF were soaked in the various media for 2, 8 and 24 h at room temperature. A control group was incubated with culture medium at 37 degrees C. After incubation, viability of the cells was determined by trypan blue exclusion test. Viable cells were then analyzed for mitogenic (with thymidine) and clonogenic capacity (by culturing one cell/well). Viability of PDLF stored up to 24 h was comparable in all tested media, and the differences were limited to 1%-3%. PDLF stored for up to 24 h in various media had statistically comparable mitogenicity to the control group. After 8 h of storage, the differences were limited to 2%-9%, except for the alpha-MEM group which had 23%-29% lower mitogenic capacity compared to the control group. Increasing the storage time up to 24 h further decreased the mitogenicity of the cells by 22% 47%. The highest mitogenicity after 24 h of storage was found in PDLF stored in culture medium or HBSS, and the lowest in alpha-MEM. PDLF stored for 2-8 h in various media had a comparable clonogenic capacity to the control group. However, after 24 h, the cells' clonogenic ability dropped by 14%-66%. A similar trend of reduction was noted in the mitogenic and clonogenic capacity, although it was statistically significant only in the clonogenic capacity. Culture medium and ViaSpan, followed by HBSS, were the most effective in preserving the clonogenic capacity of PDLF after 24 h of storage. The lowest clonogenic capacity after 24 h of storage was in the alpha-MEM group (66%, P < 0.0025). In conclusion, culture medium, followed by HBSS and ViaSpan, was the most effective media for preserving the viability, mitogenicity and clonogenic capacity of PDLF stored for up to 24 h at room temperature. The lowest functional abilities were found in PDLF stored in alpha-MEM. PMID- 11202860 TI - Postoperative discomfort associated with surgical and nonsurgical endodontic retreatment. AB - Endodontic retreatment decision-making must include an appraisal of the costs of the different strategies proposed. In addition to direct costs, postoperative discomfort may have other consequences in terms of time off work, unscheduled visits and suffering. To establish a foundation for the appraisal of such indirect and intangible costs the present study was set up in which patients' assessments of pain and swelling after surgical and nonsurgical retreatment procedures were recorded. Ninety-two patients with 95 root-filled incisors and canine teeth exhibiting apical periodontitis were included in the study. The mode of retreatment was randomly assigned. Each day during the first post-treatment week patients assessed their degree of swelling and pain on horizontal 100-mm visual analog scales (VAS). The scales ranged from "no swelling" to "very severe swelling" and "no pain" to "intolerable pain", respectively. Consumption of self prescribed analgesics and time off work were also recorded. Significantly more patients reported discomfort after surgical retreatment than after nonsurgical procedures. High pain scores were most frequent on the operative day while swelling reached its maximum on the first postoperative day followed by progressive decrease both in frequency and magnitude. Postoperative symptoms associated with nonsurgical retreatment were less frequent but reached high VAS values in single cases. Analgesics were significantly more often consumed after periapical surgery. Patients reported absence from work mainly due to swelling and discoloration of the skin. This was found to occur only after surgical retreatment. Conclusively, surgical retreatment resulted in more discomfort and tended to bring about greater indirect costs than nonsurgical retreatment. PMID- 11202861 TI - Evaluation of the Trifecta obturating technique. AB - The aim of this project was to evaluate and compare the radiographic quality and sealability of root fillings in extracted human teeth using lateral condensation of gutta-percha or the Trifecta obturating system. One hundred freshly extracted human mature, single-rooted teeth were divided into four identical groups of 25 teeth on the basis of root canal shape. The root canals of two groups were prepared in such a way as to produce a relatively parallel canal shape with little or no flare towards the coronal orifice. The root canals of the other two groups were prepared in such a way as to produce a canal shape that was deliberately more flared to ensure that they were wider at the orifice than at the endpoint of the preparation. All root canals were flushed with 17% EDTA solution and 2.5% NaOCl to remove the dentinal smear layer. The canals of one flared and one parallel group were obturated using cold lateral condensation and the canals of the other two groups were obturated using the Trifecta system. The sealability of each technique was assessed by a dye penetration method. The radiographic quality of obturation was determined for each canal using a 4-point scale. Canals filled with thermoplasticised gutta-percha had significantly less apical dye penetration than those obturated by lateral condensation (P < 0.001). Lateral condensation achieved significantly better scores for radiographic quality than thermoplasticised gutta-percha from both the bucco-lingual (P < 0.001) and the mesio-distal views (P < 0.001). Root canals obturated using the Trifecta technique showed significantly more apical extrusion of sealer than those obturated by lateral condensation (P < 0.001). Under laboratory conditions the Trifecta technique had better sealability but poorer radiographic quality than lateral condensation. PMID- 11202862 TI - Extraradicular infection: a methodological study. AB - Whether bacteria live or die in periapical lesions of endodontic origin is debated. Sampling of periapical bacteria is difficult due to possible contamination from the indigenous microflora. The aim of this study was to examine whether bacteria were present in periapical lesions of asymptomatic teeth before sampling or were transferred there during sampling. Thirty patients with root-filled teeth and periapical radiolucencies were divided into two groups, each containing 15 patients. In Group 1, a marginal incision was made to explore the periapical lesion. In Group 2, a submarginal incision was made. Before incision, the gingiva and mucosa were washed with 0.2% chlorhexidine gluconate. Bacterial samples were taken from the mucosa before reflecting the flap, and from the alveolar bone and the periapical lesion immediately after. All samples were cultured anaerobically on all-purpose and selective media. In Group 1, 12 of the 15 patients (80%) yielded bacteria from their mucosal samples despite the chlorhexidine wash. Bacterial growth was observed in all samples (100%) from the alveolar bone while the periapical lesions gave bacterial growth in 11 of 15 cases (73%). In Group 2, bacteria were cultured from the mucosa in 11 of 15 (73%) patients. Three samples (20%) from the alveolar bone and 10 from the periapical lesions (67%) gave positive growth. The predominant cultivable bacteria were anaerobic. Phenotypic profiling, performed with the data-based API bioMerieux system, indicated that the sampling technique used prevented mucosal bacteria from reaching the exposed bone and the periapical lesions. Profiling also indicated that following marginal incision, bacteria from the periodontal pocket might have reached the underlying tissues by surgeon-released bacteremia or direct translocation. Most organisms detected in the periapical lesions were clearly different from the bacteria present at neighboring sites and appeared to have been there before sampling. PMID- 11202863 TI - Crown dilaceration of a first premolar caused by extraction of its deciduous predecessor: a case report. AB - This report describes a rare case of crown dilaceration of the mandibular first premolar caused by trauma during extraction of the precedent primary first molar. The mandibular first primary molar had been extracted at the age of 4 years 7 months. Compared to the pre-operative radiograph, the post-operative film showed that the direction of the first premolar tooth germ had changed, suggesting that crown dilaceration had been induced by the surgical procedures during tooth extraction. From radiographic examinations, the premolar was considered to have erupted spontaneously. PMID- 11202864 TI - A survey of interfacial forces used during filing of root canals. AB - The pattern of dentine removal during endodontic instrumentation is influenced by many factors including the interfacial forces applied by the operator. The aim of this study was to investigate the influence of operators and different sizes and types of instruments on the magnitude of these interfacial forces. Single-rooted teeth were mounted on a cantilevered aluminium beam to which two pairs of single element strain gauges were joined in a half-bridge configuration and mounted at right angles to each other. The strain gauges were connected to an analogue-to digital converter fitted in a micro-computer via conditioning amplifiers. This enabled strains to be recorded over a period of time. Twenty operators instrumented root canals using a series of hand instruments for 1 min each. The mean interfacial forces used by operators demonstrated a wide variation ranging from 9.06 g to 149.42 g (range of forces from 0-331 g) but there was a consistency in the relative magnitude for each operator. The 20 operators could be divided into 13 groups which were significantly different (alpha = 0.05) from each other. There were significant differences (alpha = 0.05) between the forces used for each of the K-Flex files (15, 25, 35, 45, and 70), the force increasing with the file size. There was also a significant difference (alpha = 0.05) in the forces used between the Flexofile (#25) and the #25 K-Flex and Hedstrom files. However, there was no significant difference between the K-Flex and Hedstrom files. PMID- 11202865 TI - Protective effect of Copalite surface coating on mercury release from dental amalgam following treatment with carbamide peroxide. AB - The effect of Copalite coating on mercury release from dental amalgam following treatment with 10%, 20%, 30% and 40% carbamide peroxide was assessed in vitro, using a cold-vapour atomic absorption Mercury Analyzer System. Eighty samples of dental amalgam were automatically mixed in a dental amalgamator and condensed into silicon embedding molds. Forty amalgam samples were coated with three uniform layers of Copalite intermediary varnish and the other 40 samples were left uncoated. The coated and non-coated amalgam samples were exposed for 24 h to 10%, 20%, 30% or 40% carbamide peroxide preparations and compared with samples exposed to phosphate buffer. In the non-coated samples a significant increase of mercury concentration in solution was found following exposure to all carbamide peroxide preparations tested. Mercury concentration was directly related to carbamide peroxide concentration. In the Copalite-coated samples, significantly lower concentrations of mercury in solution were found as compared to the non coated samples (P < 0.01). In conclusion, exposure of amalgam restorations to 10% 40% carbamide peroxide-based bleaching agents increased the mercury release. Pre coating of the external amalgam surfaces with Copalite significantly reduced the release of mercury. PMID- 11202866 TI - Profile of an orthodontic patient at risk of dental trauma. AB - Increased overjet and inadequate lip coverage of the maxillary incisors are considered significant risk factors in many clinical studies. The purpose of the present study was to examine this issue of dental injury by actual cephalometric measurements in orthodontic patients. Pretreatment cephalograms (taken with lips in repose) of consecutive patients were used. The patients were allotted to two groups Group T (trauma): 56 patients who had injured their maxillary incisors prior to their orthodontic treatment, mean age at the start of treatment 11.9 years (SD = 1.5); and Group C (control): 98 patients with intact maxillary incisors, mean age at the start of treatment 11.6 years (SD = 1.3). Twelve cephalometric landmarks on the soft and hard tissue profile were identified and digitized and the relevant dental, skeletal and soft tissue measurements recorded. The variables in Groups T and C were compared and their predictive values for possible occurrence of trauma were tested by logistic regression analysis. No statistically significant differences between boys and girls were found. Overjet or maxillary incisor exposure or interlabial gap, each as a single variable, could differentiate between the two groups. Logistic regression analysis indicated that only a small percentage (28.7%) of the dependent variable variation (trauma vs control) can be explained by interlabial gap, gender, upper incisor long axis to facial plane (degree), upper incisor long axis to interlabial gap and overjet. PMID- 11202867 TI - Comparison of different techniques for obturating experimental internal resorptive cavities. AB - Forty extracted maxillary central incisors were instrumented at the working length to a #50 file. The roots were sectioned transversely with a diamond disk at 7 mm from the anatomical apex. At the opening of the root canal of each section, hemicircular cavities were drilled with a specially designed bur. The corresponding root sections were cemented with glue, thus obtaining root canals with similar cavities that simulated internal resorptions. Teeth were embedded in plaster casts to facilitate their handling. The specimens were randomly separated into four groups of 10. The following obturation techniques were evaluated: lateral compaction (group A), hybrid technique (group B), Obtura II (group C), and Thermafil (group D). AH26 was used as the sealer. After obturation, the plaster was removed and the teeth were radiographed in buccolingual and mesiodistal directions to evaluate the quality of the obturation at the IRC. The incisors were then cut with a scalpel at the same level as the previous section, to examine, under a stereomicroscope, the type of material that filled the IRC. Obtura II gave the best results and in most of the specimens obturated with this technique, the IRC were filled mainly with gutta-percha. Statistical analysis of the data indicated that the differences between group C and the other groups were significant (P < 0.05). PMID- 11202868 TI - Traumatic dental injuries and Alpine skiing. AB - The purpose of this study was to determine the occurrence and type of traumatic dental injuries after maxillofacial injuries as a result of Alpine skiing. During an 8-year period (from January 1991 to December 1998) 7600 patients with facial injuries were registered at the Department of Oral and Maxillofacial Surgery, University of Innsbruck, Austria. Of 784 patients with skiing-related facial injuries (524 males, 260 females) 326 (41.6%) sustained injuries to 639 teeth. The age groups predominantly affected were between 7 and 32 years. Luxation injuries occurred in 338 (53%) teeth, fractures accounted for 270 tooth injuries (42%), and only 35 (5%) were lost at the place of the accident. Of skiers with traumatic dental injuries 58% had concomitant soft tissue injuries, while 23.3% had associated facial bone fractures. The most common causes of injury were falls in 42% (329 patients) and collisions with other persons in 24.1% (189 patients). Being hit by one's own sports equipment (11%) was the third most common cause. Collisions with obstacles accounted for 9% and lift accidents for 5.6% of injuries. The probability of suffering dentoalveolar trauma during skiing varied depending on the injury mechanism. There was a 2-fold risk for dentoalveolar trauma when colliding with objects, a 3.5-fold risk when hit by one's own equipment and a 8.5-fold risk during lift accidents. Dental injuries occurred in about 2% of all injured skiers. Dental health professionals should be aware of the high incidence and the distribution of dental trauma and facial injuries caused by skiing. PMID- 11202869 TI - Utilization of gutta-percha for retrograde root fillings. AB - Just as gutta-percha used with a root canal sealer is a recommended material for orthograde root fillings, it could similarly be the material of choice for retrograde fillings. Unfortunately, clinical accessibility and visibility do not always facilitate such a technique. The aim of this article is to present a new technique which enables retrograde fillings to be achieved with gutta-percha and a sealer. After the apex had been resected, a hole was drilled perpendicular to the plane of section of the apex about 1 mm coronally. The bucco-lingual depth required to reach the main canal was calculated. The cavity was then dried, coated with the sealer, and obturated with gutta-percha in accordance with thermo mechanical compaction techniques. After excess filling material had been removed, the gutta-percha was cold burnished and the angles of the root were smoothed. Clinical cases illustrating healing of the periapical tissues are shown. PMID- 11202870 TI - Malformations in maxillary incisors: case report of radicular palatal groove. AB - This report describes malformations of anterior teeth and a case of a palatal radicular groove in an upper lateral incisor with periodontal complications. The patient was first diagnosed with an endodontic problem. Endodontic treatment alone failed to resolve the pain. Therefore, after the palatal groove had been properly diagnosed, a palatal flap procedure was carried out including removal of the granulation tissue and careful scaling and root planing of the area with the groove. No odontoplasty was done. Endodontic therapy of the tooth was completed and periapical healing was evident. The treatment effectively reduced the gingival probing depth and led to an asymptomatic tooth. PMID- 11202872 TI - Rationale for the use of low-torque endodontic motors in root canal instrumentation. AB - Fracture of nickel-titanium rotary files is an iatrogenic error which can seriously jeopardize root canal therapy. If a high-torque motor is used, the instrument-specific limit-torque (fracture limit) is often exceeded, thus increasing the risk of intracanal failure. A possible solution to this problem is to use a low-torque endodontic motor which operates below these values. If the torque is set just below the limit of elasticity for each instrument, the risk of fracture is likely to be markedly reduced. The purpose of this paper was to discuss mechanical properties of NiTi rotary instruments, the rationale for selecting low torque values, and to use clinically a new endodontic motor (step motor) which operates below the limit of elasticity of each rotary file. The step motor was found to be helpful in reducing the risk of instrument fracture. Irreversible material damage (plastic deformation) and instrument fracture were rarely seen. Low-torque instrumentation also increased tactile sense and, consequently, mental awareness of rotary instrumentation. PMID- 11202871 TI - A multidisciplinary treatment approach to a complicated maxillary dental trauma: a case report. AB - This case report describes the treatment of an 18-year-old male who lost two central maxillary incisors due to dental trauma. Because of a deep overbite and serious occlusal instability, the lost teeth 11 and 21 could not be replaced by a conventional fixed prosthesis. The vertical dimension of occlusion was increased using a Hawley-type appliance over a period of 1 year. When sufficient intermaxillary space was gained the alveolar ridge was augmented with a mandibular symphysis graft. Nine months later two one-stage non-submerged implants (ITI, Straumann, Waldenburg, Switzerland) were inserted. After further soft tissue adaptation to two temporary acrylic crowns, porcelain veneers were placed on the two implants and the lateral incisors. PMID- 11202873 TI - The lateral periodontal cyst: aetiology, clinical significance and diagnosis. AB - The lateral periodontal cyst (LPC) is a relatively uncommon but widely recognized odontogenic cyst of developmental origin. It is found mostly in adults and has no sex predilection. LPC is usually discovered during routine radiographic examination, is located mainly between the roots of vital mandibular canines and premolars, and seldom causes pain or other clinical symptoms. The defect appears on radiographs as a round or teardrop-shaped, well circumscribed radiolucency. Due to its location it can easily be misdiagnosed as a lesion of endodontic origin. In this paper, two cases of lateral periodontal cysts are presented. In the first case, the patient (woman, 62 years old) complained of an asymptomatic gingival swelling in the region between the right maxillary canine and premolar. The radiographic examination revealed a well circumscribed radiolucency with a radiopaque margin between the roots of the canine and premolar. The adjacent teeth had vital pulp. Surgical enucleation of the lesion was performed and the histological examination revealed that the lesion was a "lateral periodontal cyst of developmental origin". In the second case, the patient (women, 44 years old) complained of a swelling in the area of tooth 32. During radiographic examination a well circumscribed radiolucency between the roots of the lateral incisor and the canine was discovered. Surgical enucleation of the lesion was performed and the histological examination revealed that the lesion was a "lateral periodontal cyst of developmental origin". PMID- 11202875 TI - Radiographic analysis of the development of periapical lesions in normal rats, sialoadenectomized rats and sialoadenectomized-immunosuppressed rats. AB - The purpose of this study was to investigate and to compare radiographically the development of periapical lesions in the lower left first molar of normal rats, sialoadenectomised rats and sialoadenectomised-immunosuppressed rats. Sixty male Wistar rats, weighing from 170 to 200 g were utilized. The animals were divided equally into three groups: group I--20 normal rats; group II--20 sialoadenectomised rats; and group III--20 sialoadenectomised-immunosuppressed rats. Groups II and III were sialoadenectomized using the modified Cheyne technique. After 2 weeks, group III was submitted to a immunosuppression regimen by daily subcutaneous cyclosporin A injection (10 mg/kg body weight). After 1 week of immunosuppression for this group, the pulps of all the animals (group I, II and III) were exposed to the oral cavity, to produce apical periodontitis. Five animals of each group were killed 7, 14, 21 and 28 days after pulpal exposure. Their mandibles were surgically removed and radiographically analysed. The lesions were measured using 'Global Lab Image' software. The results showed predictable growth of the lesions during the experimental period. No significant difference was observed between the groups. It was concluded that possible changes in the oral flora and in the host immune response due to xerostomia associated or not to the immunosuppression did not alter the development of the periapical lesions in rats. PMID- 11202874 TI - Impact strength of teeth restored by fragment-bonding. AB - The objective of this in vitro study was to investigate the impact strength of anterior teeth that have been fractured and restored by bonding with a dentin bonding agent and a composite resin. Twenty sheep central incisors were divided into two groups, 10 in each. One group (intact teeth) served as the control and the teeth in the other group were fractured and then bonded with a bonding agent and a low-viscous composite resin. The specimens were tested in a modified impact testing machine (pendulum type). The mean impact strength of the intact teeth was 30.6 +/- 2.16 KJ/m2 and of the bonded teeth was 30.2 +/- 1.86 KJ/m2. Statistics revealed that the two means were not significantly different. The results related well with the fracture strength obtained by loading intact and bonded teeth at constant but low speed until fracture. It was concluded that bonding fragments to the remaining tooth structure may restore the tooth to its original strength, measured at modest velocities of the applied force. In other words, reattaching the original coronal fragment of traumatised fractured anterior teeth restored with One-Step dentin bonding system and AEliteflo composite resin would withstand a second trauma to the same extent as intact teeth. PMID- 11202876 TI - An in vitro investigation into the cutting action of ultrasonic radicular access preparation instruments. AB - The aim of this study was to investigate the dentine cutting action of a CT4 and SJ4 radicular preparation inserts (Excellence in Endodontics/Analytic Technology, Orange, CA, USA) used in a Piezon Master 400 ultrasonic handpiece (Electro Medical Systems SA, Nyon, Switzerland). Calibration of the ultrasonic inserts was carried out at minimum, medium and maximum power settings using light microscopic measurement of the tip displacement amplitudes (x120 mag). Polished dentine samples were instrumented, at monitored loads, at the three chosen power settings, to produce uniform dentine cuts. The resultant dentine debris was collected for SEM analysis, and comparison with that produced by rotary instruments. The depth of dentine cut was measured at x30 magnification. Fracture of the SJ4 insert was noted at medium power setting. Results revealed a significant increase in both displacement amplitude and depth of dentine cut with power setting (ANOVA P < 0.001). Dentine chip size increased with power, and differed in structure and appearance from those produced by rotary instruments. In conclusion, ultrasonic cutting is influenced significantly by power setting, and dentine chip formation is fundamentally different to rotary instrumentation. PMID- 11202877 TI - The aetiology of dento-alveolar injuries and factors influencing attendance for emergency care of adolescents in the north west of England. AB - The aims of the study were to determine the main aetiological factors involved in injuries to anterior teeth and to identify factors influencing the attendance for emergency care. This information is essential, first, for planning dental health education programmes aimed at reducing the incidence of dental trauma and, second, to devise strategies for its effective treatment. Of 2022 schoolchildren examined for evidence of dental trauma, 696 (34%) had experienced injury and were interviewed regarding this injury. Of these, 403 knew about their damaged front tooth, but only 330 recollected the incident causing the injury. Over one third of accidents occurred at home and a further 25% at school. The most common cause of injury was falling onto a hard surface or object (34%) with accidents involving bicycles or other sporting activities accounting for a further 30%. Factors found to be significantly related to attendance for emergency care were experience of pain, unattractive appearance of the injured tooth and social classification, with children from higher income, more affluent areas being more likely to seek treatment. The majority of dental injuries were the result of genuine accidents which were almost impossible to prevent. This study highlighted the need for attention to be brought to parents, children, lay people and health care professionals that all dental injuries should be examined by a dentist, not just those injuries resulting in pain or poor aesthetics. PMID- 11202878 TI - The influence of interfacial forces and duration of filing on root canal shaping. AB - The aim of this study was to investigate the possible relationship between interfacial forces, duration of instrumentation and effectiveness of root canal shaping by filing. All factors were standardised except the manner of manipulation of the files and the dependent variables (interfacial force and duration of filing). The outcome measured was the final prepared canal shape. The study tested the hypothesis that if interfacial forces and duration of filing had predictive value for effective canal shaping, a relationship between them should be apparent. If it was not, it could be inferred that the remaining uncontrollable variable, "manner of file manipulation" had a dominating influence. 18 operators used a standard filing technique to instrument a root canal each in single rooted teeth matched for anatomy. The teeth were mounted in a custom-made transducer designed to measure laterally applied interfacial forces between file and dentine. The length of time taken with each instrument in the series was measured giving a total duration of instrumentation. The final canal shape measured by standardised "before" and "after" radiographic images of the roots was judged against an "ideal" canal shape calculated from the size of instruments used and based on the preliminary canal shape. Although some trends were revealed, no obvious relationship was demonstrated between interfacial force, duration of filing and final canal shape. Operators clearly used a range of interfacial forces characteristic for each individual and for the different file sizes. Both light and heavy forces could produce a satisfactory canal shape. Use of light or heavy forces did not obviously affect speed of preparation. Tactile discrimination was not dependent on use of light or heavy forces. It was inferred that the "manner of file manipulation" remained undefined and was probably the dominant factor influencing outcome of canal shaping. PMID- 11202879 TI - Prognosis of replanted primary incisors after injuries. AB - Between 1979 and 1997, 58 avulsed primary teeth were treated at the Pedodontic Clinic of Niigata University Dental Hospital. Among these, we replanted six avulsed incisors of four patients and treated two teeth of two patients replanted at other dental clinics. Referring to the clinical records, oral photographs and radiographs, we examined the injury age, cause of injury, condition of tooth storage, length of time until replantation, and also the prognosis after replantation. Three teeth of two cases remained until eruption of their permanent successors, and one tooth of one case remained under observation without extraction. Although the other four teeth of three cases resulted in extraction, no secondary infection was detected due to replantation. The following reasons were suspected for the poor prognosis of the four teeth. One avulsed tooth was not fixed immediately after replantation. One replanted tooth might not have been compatible with the alveolar socket. In the other two teeth, the periodontal vital tissues might have been removed before replantation. It is generally suggested that replantation of primary teeth is not a good option. However, from the present results, it was considered that replantation can be an effectual method when the condition of the avulsed primary tooth is suitable. PMID- 11202881 TI - Assessment of periradicular microbiota by DNA-DNA hybridization. AB - In the present study the "checkerboard" DNA-DNA hybridization technique was used to identify bacteria in periapical endodontic lesions of asymptomatic teeth. Thirty-four patients with root-filled teeth and apical periodontitis were divided into two groups, each containing 17 patients. In Group 1, a marginal incision was performed during surgery to expose the lesion, and in Group 2, a submarginal incision was applied. The gingiva and mucosa were swabbed with an 0.2% chlorhexidine gluconate solution prior to surgery. Bacterial DNA was identified in all samples from the two groups using 40 different whole genomic probes. The mean number (+/- SD) of species detected was 33.7 +/- 3.3 in Group 1 and 21.3 +/- 6.3 in Group 2 (P < 0.001). The majority of the probe-detected bacteria were present in more lesions from Group 1 than from Group 2. The differences were most notable for Campylobacter gracilis, Porphyromonas endodontalis, Propionibacterium acnes, Capnocytophaga gingivalis, Fusobacterium nucleatum ssp. nucleatum, Fusobacterium nucleatum ssp. polymorphum, Prevotella intermedia, Treponema denticola, Streptococcus constellatus and Actinomyces naeslundii I. Bacterial species such as Actinobacillus actinomycetemcomitans and Bacteroides forsythus were detected in more than 60% of the lesions from both groups. Also, P. endodontalis was abundant in periapical tissue. The data supported the idea that following a marginal incision, bacteria from the periodontal pocket might reach the underlying tissues by surgeon-released bacteremia. The study provided solid evidence that bacteria invade the periapical tissue of asymptomatic teeth with apical periodontitis. The detection of much more bacteria with the "checkerboard" DNA-DNA hybridization method than has previously been recovered by anaerobic culture indicated that the endodontic (and periodontal) microfloras should be redefined using molecular methods. PMID- 11202880 TI - Immunologic evaluation of dental patient with history of hypersensitivity reaction to sodium hypochlorite. AB - A 12-year-old girl, with a previous history of bronchial reaction and contact dermatitis to sodium hypochlorite, was referred for root canal treatment. Complete immunologic evaluation revealed a mild hypersensitivity condition, as it was assessed by the RAST investigation to different allergens and the DTH reactivity expressed though migration inhibition test. The absence of a serious immunologic disregulation in the patient's immunologic profile justified the term 'non-allergic hypersensitivity' to sodium hypochlorite to describe the condition. PMID- 11202882 TI - Bacteria of asymptomatic periradicular endodontic lesions identified by DNA-DNA hybridization. AB - Possible inclusion of contaminant bacteria during surgery has been problematic in studies of periradicular lesions of endodontic origin. Therefore, in this study, two different surgical techniques were compared. A second problem is that some difficult to cultivate species may not be detected using bacteriological methods. Molecular techniques may resolve this problem. DNA-DNA hybridization technology has the additional advantage that DNA is not amplified. The purpose of this investigation was to determine if bacteria from periradicular endodontic lesions could be identified using DNA-DNA hybridization. A full thickness intrasulcular mucoperiosteal (IS) flap (n = 20) or a submarginal (SM) flap (n = 16) was reflected in patients with asymptomatic apical periodontitis. DNA was extracted and incubated with 40 digoxigenin-labeled whole genomic probes. Bacterial DNA was detected in all 36 lesions. Seven probes were negative for all lesions. In patients with sinus tract communication, in teeth lacking intact full coverage crowns, and in patients with a history of trauma 4-13 probes provided positive signals. Seven probes were positive in lesions obtained by the IS, but not the SM technique. Two probes were in samples obtained with the SM technique, but not the IS. Only Bacteroides forsythus and Actinomyces naeslundii genospecies 2 were present in large numbers using either the IS or the SM technique. The SM flap technique, in combination with DNA-DNA hybridization, appeared to provide excellent data pertaining to periradicular bacteria. These results supported other studies that provide evidence of a bacterial presence and persistence in periradicular lesions. PMID- 11202883 TI - Risk evaluation and type of treatment of multiple dental trauma episodes to permanent teeth. AB - Studies have shown that some children and adolescents are effected only once with a dental trauma, while others seem to be accident-prone and suffer from multiple dental trauma episodes (MDTE). Studies have also shown that dental traumas mostly affect upper permanent and medial incisors. Less is known about treatment consequences related to teeth with repeated dental trauma episodes. The aim was therefore to evaluate the risk of MDTE to permanent teeth among children and adolescents by age and gender and to compare types of dental treatment modalities used for patients with one episode and those with MDTE and with single and repeated traumatized teeth. The study was based on a random sample of 83 Danish 6 18-year-old children and adolescents born in 1970 who suffered from dental trauma episodes. All patients were followed during a 12-year period (1976-1988). Forty one of the patients were registered with MDTE with a range of 2-7 episodes and a mean of 2.9 episodes/patient (SD = 1.1). The mean age at single and MDTE was 11.4 years (SD = 3.6) and 8.6 years (SD = 2.1), respectively. No significant differences were found between age at first episode and the number of MDTE per patient. The number of patients with MDTE was significantly higher among those who suffered their first trauma episode in the age interval 6-10 years than in the age interval 11-18 years (P < 0.001). A survival analysis showed that the risk of sustaining another trauma episode increased by 14.9-30.3% when the first trauma occurred before the age of 11, compared to 0-7.4% after the age of 10. The risk of sustaining multiple injuries was 8.4 times higher when the first trauma episode occurred at 9 years of age, compared with those occurring at age 12. The survival analysis also showed that for every new trauma episode, the interval between them became closer. Forty-five per cent of the MDTE affected teeth had already sustained an injury. With an increased number of trauma episodes per patient followed an increase in the number of follow-ups, filling therapy, information and prosthetics, whereas the rates of endodontics, surgery, and consultations were unchanged or even decreased. PMID- 11202884 TI - Pulp revascularization of replanted immature dog teeth after different treatment methods. AB - The purpose of the present study was to determine the effect of topical treatment with doxycycline and/or the application of unfilled resin to the anatomical crown on the occurrence of revascularization in reimplanted dog teeth. Ninety-six teeth in 4 young mongrel dogs were used. Eighty one teeth were atraumatically extracted and divided into four groups. Group 1, 17 teeth were kept dry for 5 min and then replanted. Group 2, 21 teeth were soaked with a freshly prepared solution of doxycycline (1 mg/20 mL saline) for 5 min before replantation. Group 3, 23 teeth were soaked with the doxycycline solution for 5 min, and then replanted. The crowns were coated with 2 layers of light cured unfilled resin. Group 4, 20 teeth were kept dry for 5 min, and then replanted. The crowns were treated as with the teeth in Group 3. Three months after surgery, radiographic evaluation revealed that 27 teeth had continued root development and 32 teeth showed arrested root development with periradicular pathosis. The remaining 17 teeth, which had arrested root development but no signs of periradicular pathosis, were all histologically evaluated for final assessment. The occurrence of revascularization according to treatment group was 29.4%, 60%, 60%, 36.8% in Group 1, 2, 3, and 4, respectively. A multiple logistic regression analysis in SAS indicated there was no significant association between vitality and dog (P = 0.7564). Soaking for 5 min in doxycycline significantly increased the revascularization rate (P = 0.024) while the addition of resin to the crown did not result in an increased incidence of pulp revascularization (P = 0.823). PMID- 11202885 TI - Influence of coronal restorations on the periapical health of endodontically treated teeth. AB - The purpose of the study was to evaluate a possible relationship between the quality of the coronal restoration, the root canal obturation and the periapical status of endodontically treated teeth. Full mouth series of radiographs from randomly selected patient charts at the Dental Faculty, University of Oslo were examined. A total of 1001 endodontically treated teeth restored with a permanent restoration were evaluated independently by two examiners. According to a predetermined set of radiographic criteria, the technical quality of the root filling of each tooth was scored as either good (GE) or poor (PE), and the technical quality of the coronal restoration was scored as good (GR) or poor (PR). The root and the surrounding structures were then evaluated and according to the periradicular findings, the treatment was categorized as success or failure. The success rate for all endodontically treated teeth was 67.4% (n = 1001). Teeth with root canal posts had a success rate of 70.7% (n = 527) and teeth without posts had a success rate of 63.6% (n = 472). The two groups with technically good endodontics had the highest success rates. In combination with technically good restorations the success rate was 81% (GE + GR, 81%) and combined with technically poor restorations the success rate was 71% (GE + PR, 71%). The two groups with technically poor endodontics combined with either good restorations or poor restorations had significantly lower success rates (PE + GR, 56% and PE + PR, 57%). The technical quality of the endodontic treatment as judged radiographically was significantly more important than the technical quality of the coronal restoration when the periapical status of endodontically treated teeth was evaluated. PMID- 11202886 TI - Urinary catecholamine levels and incidence of dentofacial injuries in children: a 2-year prospective study. AB - Urinary catecholamines have been used to measure emotionally stressful states which may have an impact on dentofacial injuries. This prospective study investigated the hypothesis that urinary catecholamines such as epinephrine, norepinephrine and dopamine do not affect significantly the incidence of dentofacial injuries in children. As a test of this hypothesis 204 children, males and females, aged 8 to 10 years, were included in the study. After a first examination, each subject was re-examined, at one-year intervals, over a period of two years. Dentofacial injuries were recorded by a clinical examination and a questionnaire. Three 24-h urine samples, with an interval of one year between each, were collected and analyzed by the high performance liquid chromatography technique to assay the catecholamine content. Socio-economic factors were recorded by a questionnaire. Using the panel of data collected, the logistic multiple regression model was employed to test whether the incidence of dentofacial injuries was affected by the studied variables. The 95% probability level was used. Specificity and sensitivity as well as the positive and negative predictive rates were computed. The results showed that epinephrine had a significant correlation with the incidence of dentofacial injuries. Other factors found to have a significant impact were child's age and gender. The values of sensitivity and specificity were 81% and 69% respectively, while the positive and negative predictive rates were 68% and 82% respectively. The data, therefore, provided evidence that emotionally stressful states measured by the urinary catecholamines were prominent etiologic factors of dentofacial injury. PMID- 11202887 TI - Factors associated with root canal ledging during instrumentation. AB - The purpose of this study was to identify the presence of a ledge in 141 cases treated in an undergraduate clinic and in 103 cases treated by endodontists, and to identify the clinical factors associated with ledging. A total of 626 root canals were examined and the factors analyzed were canal location, tooth number and canal curvature. The results indicated that 51.5% of the canals treated by students had been ledged, whereas the percentage was 33.2% for intact pulp cavities treated by endodontists and 40.6% in cases of endodontic retreatment. Canal location was found to have an effect on the incidence of ledging as the mesiobuccal, mesiolingual and distal buccal root canals exhibited a significantly higher ledge incidence rate than the distal and palatal root canals. Canal curvature was the most significant variable affecting the incidence of ledging. PMID- 11202888 TI - Tongue piercing and associated oral and dental complications. AB - The insertion of metal objects into intraoral and perioral sites is growing in popularity. However, there are numerous oral and dental complications associated with tongue piercing. Fifteen patients with tongue piercings (pierced in the body of the tongue, anterior to the lingual frenum) attending the dental office of the authors, with and without complaints, were clinically and radiographically examined. The most common dental problem registered was chipping of teeth. Furthermore, two cracked teeth and four teeth with cusp fractures were also seen. One case of selective dental abrasion was registered. Trauma to the lingual anterior gingiva was the most common gingival problem. A salivary flow stimulating effect was only reported by 2 of the 15 individuals. None of the patients complained of interference with speech, mastication and swallowing. One case of galvanic currents produced by the appliance was registered. On the basis of the registered data, we concluded that patients need to be better informed of the potential complications associated with tongue and oral piercings, and that the dental profession can serve this role. PMID- 11202889 TI - Pulp capping with adhesive resin-based composite vs. calcium hydroxide: a review. AB - The results of some short-term experiments suggest that direct capping of a vital pulp with the modern resin-based composite systems may be as effective as capping with calcium hydroxide. Total cavity etching with 10% phosphoric acid seems to be safe for the exposed pulp, but unless annulled by calcium hydroxide 35% phosphoric acid may be disastrous. For hemostasis and cleaning of the pulp wound both sodium hypochlorite and saline seem suitable, whereas the effectiveness of a 2% chlorhexidine solution is questionable. Although hard-setting calcium hydroxide cements may induce the formation of dentin bridges, they appear not to provide an effective long-term seal against bacterial factors. Within a few years, the majority of mechanically exposed and capped pulps show infection and necrosis due to microleakage of such capping materials and tunnel defects in the dentin bridges. It is unknown whether newer types of resin containing calcium hydroxide-products will act as a permanent barrier. The cytotoxicity of the resin based composites and the temperature rise during polymerisation may not be of concern, but microleakage, sensitisation and allergic reactions may pose problems. Based on available data, pulp capping with resin-based composites may be said to be promising, but more and long-term research is mandatory before the method can be recommended. PMID- 11202890 TI - The influence of sample dimensions on hydroxyl ion release from calcium hydroxide products. AB - The purpose of this study was to compare the rate of hydroxyl ion release from commercially available setting and non-setting calcium hydroxide products. The rate of hydroxyl ion release is important, as this has been suggested to be the main factor in the therapeutic activity of these products. In total, hydroxyl ion release was measured from 1104 samples of Dycal, Life, Calasept and Hypocal in solution using in vitro titration. The rate of hydroxyl ion release was measured for up to 14 days, using two sizes of sample surface area. The dimensions of the exposed sample surface area was found to be an important physical constraint to the hydroxyl ion release from non-setting calcium hydroxide products, whereas this was not found to be the case with setting products. The range in hydroxide activity between products was found to be 298%. In rank order of hydroxide ion release, from the most to the least active was: Hypocal, Calasept, Life and Dycal. The differences in the rate of hydroxyl ion release from these products may have some implications for their clinical applications. It is suggested that in cases where the oral healing responses have been poorer than expected, the size and seal of prepared cavities could have negatively influenced the therapeutic release of hydroxyl ions from non-setting calcium hydroxide products. PMID- 11202891 TI - Dentine chips produced by nickel-titanium rotary instruments. AB - This study aimed to compare the cross-sectional shape of two nickel-titanium rotary instruments, namely ProFile and Quantec files, both ISO 25, 0.06 taper, and sought to relate this to the chips produced by cutting dentine. A limited comparison was made with stainless steel engine reamers. First, five files of each type were sectioned transversely at 12 mm, 8 mm and 4 mm from the tip and examined by scanning electron microscopy. The cutting angles were assessed by a direct measurement technique which allowed for the inclination of a cutting edge to the root canal. Second, eight samples of cutting debris were collected from instrumentation by each type of nickel-titanium file and four samples from the engine reamers. The major and minor axis, area and roundness of the dentine chips in each sample were measured using computerized particle analysis. The results demonstrated that all files had a negative cutting angle which varied at the different levels (ProFiles range 69.4 degrees to 58.4 degrees and Quantec range 74.8 degrees to 56.8 degrees). The consistency within files of the same type was good as demonstrated by low standard deviations, except for Quantec files at the 4 mm level where higher standard deviations of 4.1 degrees and 5.5 degrees for the two blades were found. The chip analysis showed significant differences between chips produced by ProFile and Quantec files (P < 0.05). The latter were larger and rounder. The chips from the ProFile and the engine reamer chips were similar in dimension (P > 0.05). No simple relationship existed between file geometry and the dentine chips produced during instrumentation. PMID- 11202892 TI - The effect of zinc oxide-eugenol on the shear bond strength of a commonly used bonding system. AB - It has been claimed that eugenol has a detrimental effect on resin composites and dentin bonding systems. The aim of the present study was to examine whether zinc oxide-eugenol (ZOE) cement would reduce the efficacy of a bonding system. Human third molars were selected for the study, and cylindrical posts of a resin composite (Z100) were bonded vertically to a standardized flat dentinal surface, prepared on the buccal surface of the teeth and treated with Scotchbond Multi Purpose. The tooth surfaces involved were either freshly cut, or had been exposed to ZOE cement for 6 days, with and without a subsequent thorough cleansing with ethanol. The bond strength in shear was measured after 24 hours. The results showed that ZOE cement had no negative effect on the bond strength of the resin composite (Z100) to dentin when this bonding system was used. The mean shear bond value for the specimens covered with ZOE cement for 6 days was 28.1 MPa. For specimens covered with ZOE cement and cleansed with 96% ethanol, the mean shear bond value was 23.5 MPa. The corresponding value for the controls was 19.0 MPa. These findings suggested that eugenol-containing temporary filling materials may be used safely prior to inserting resin based restorative materials, when Scotchbond Multi-Purpose is employed as the bonding agent. PMID- 11202893 TI - Comparison of profiles of key periodontal pathogens in periodontium and endodontium. AB - Despite the established anatomical relationship between the periodontal and pulpal tissues, bacterial migration between endodontium and periodontium is still under discussion. The objective of this study was an investigation of profiles of periodontal pathogens in pulpal and periodontal diseases affecting the same tooth by means of 16S rRNA gene directed polymerase chain reaction (PCR). 31 intact teeth with both pulp and marginal infections were investigated. The diagnosis was based on clinical and radiological examination. Samples were taken from the gingival sulcus or periodontal pocket, respectively, with sterile paper points before trepanation of the teeth. After trepanation sterile paper points and Hedstroem files were used for taking samples from the root canal. Specific PCR methods were used to detect the presence of the following pathogens: Actinobacillus actinomycetemcomitans, Bacteroides forsythus, Eikenella corrodens, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia and Treponema denticola. In addition, quantitative competitive PCR was used to determine the total bacterial count of the samples. The investigated pathogens were proven to be present in the endondontium in all disease categories. Particularly in endodontic samples of "chronic apical periodontitis" and "chronic adult periodontitis" profiles of the periodontal pathogens were found. The results confirmed that periodontal pathogens often accompany endodontic infections and supported the idea that the periodontic-endodontic interrelationships should be considered as critical pathways which might contribute to refractory courses of endodontic or periodontal diseases. PMID- 11202894 TI - Treatment of traumatic dental injuries in a cohort of 16-year-olds in northern Sweden. AB - The prevalence and yearly incidence of traumatic tooth injury between 1 and 16 years of age have been studied in a cohort of 16-year-olds, born in 1975, and residing in the County of Vasterbotten. The study material comprised 3007 dental records from the Public Dental Health Service. Of these, 1040 contained information on dental injuries. Out of 1000 injured primary teeth, 32% were lost, either avulsed at the time of the accident or extracted due to complications. A majority (92%) of the extractions was performed at the first or second follow-up. A total of 690 tooth injury episodes had occurred in the permanent dentition, involving 981 teeth. In 10% of the teeth more than one diagnosis was recorded for the same tooth. 416 restorations were performed due to crown fractures, the majority at the emergency visit. 44% of the patients had to come back one or more times to revise the composite restoration. Complicated fractures or serious luxation injuries constituted only 5% of the total number of injuries in the permanent dentition. 77 (8%) of the traumatised teeth were treated endodontically. Two percent of the teeth with uncomplicated crown fractures required endodontic treatment due to pulp necrosis, while 28% of teeth with a combination of crown fractures and luxation injury were endodontically treated. Out of 6 avulsed incisors, 4 survived after endodontic treatment. A total of 7 incisors were lost as a consequence of the injuries. A specialist treated 4% of the patients. PMID- 11202895 TI - Bacterial leakage in obturated root canals following the use of different intracanal medicaments. AB - The aim of this study was to examine whether intracanal medication prior to root canal obturation has an inhibitory effect on corono-apical penetration of bacteria. 93 single rooted teeth were instrumented and sterilized with ethylene oxide. They were assigned to three control groups and four test groups with n = 20 each. For one week, they were dressed with different medicaments: The first group with a 5% chlorhexidine gel, the second with Ledermix, the third with a fresh mix of calcium hydroxide and water and the fourth without any medication. After obturation (lateral condensation, AH26) the roots were fixed between a top and a bottom chamber. The top chamber contained 3 mL trypticase soy broth with 10(8) Staphylococcus epidermidis CFU's/mL, whereas the bottom chamber contained sterile trypticase soy broth. For one year, the mounts were incubated at 37 degrees C. They were checked on a regular basis for turbidity in their bottom chambers indicating bacterial growth. None of the test samples leaked for three months. After one year, the calcium hydroxide group had only 6 leaking samples whereas the chlorhexidine group had 14, the Ledermix group 15, and the unmedicated group had 13 leaking samples. It may be concluded that under the conditions of this study, calcium hydroxide was the medicament of choice to avoid bacterial penetration of the root canal. Ledermix did not perform better than no premedication. Chlorhexidine was superior to Ledermix in the second third of the observation period. PMID- 11202896 TI - Cytotoxic effect of four root filling materials. AB - The aim of this study was to evaluate the cytotoxic effect of four root canal sealers: AH26, AH Plus, Diaket and Apexit. In the experiment two cell lines, human cervical carcinoma (HeLa) cells and mouse skin fibroblasts (L929), were used. Under aseptic conditions, the sealers were prepared according to the manufacturers' directions, and 0.01 mL of each material was placed in a 24-well plate. The sealers were covered with cell suspension. The cytotoxicity was estimated by determining the number of viable cells by a light microscope, as well as the total number of cells 24 h, 48 h and 120 h after the treatment with mentioned materials. The results obtained in this study showed the high cytotoxcity of the new AH Plus root canal sealer, which was shown to be equally or more toxic to the standard AH26 and Diaket materials. Apexit was the least toxic sealer. PMID- 11202897 TI - The sealing ability of an epoxy resin root canal sealer used with five gutta percha obturation techniques. AB - The purpose of the present study was to evaluate the apical sealing ability of an epoxy resin root canal sealer (AH-26) when used with different gutta-percha obturation techniques (i.e. cold lateral condensation, warm vertical condensation, hybrid condensation) and with Thermafil and Soft-Core obturators. Straight single-rooted teeth with mature apices were prepared according to the crown-down/step-back technique and divided in five groups of 45 teeth and one group of 12 control teeth. After root canal filling 15 teeth of each group were kept for 1 day, another 15 teeth for 1 week, and another 15 teeth for 4 months at 37 degrees C in vacutainers in 80% relative humidity. The 237 teeth were immersed in india ink for 90 hours, each root was split and sectioned longitudinally, and the maximum extent of leakage was measured using a stereomicroscope at x6 magnification. It became clear that leakage occurred whatever technique was combined with AH26 and that leakage increased with time. The amount of apical leakage and the number of leaking teeth in the Soft-Core obturator groups was significantly higher than all other 4 gutta-percha obturation techniques combined with AH26. In this respect, the hybrid gutta-percha condensation technique turned out to be superior to the four other condensation techniques. PMID- 11202898 TI - Bone-like tissue growth in the root canal of immature permanent teeth after traumatic injuries. AB - Following a severe traumatic incident to permanent immature teeth, the growth of calcified tissue in the pulp space may occasionally occur. This calcified tissue may be diffuse or in intimate contact with the dentine. It has been suggested that a wide open apex, severe damage to the root sheath, and the absence of infection are only some of the predisposing factors leading to this metaplasia of pulp tissue into bone-like tissue. Five cases are described. PMID- 11202899 TI - Ascaris in burned patients. PMID- 11202900 TI - Recent References. PMID- 11202901 TI - Society for the Study of Behavioural Phenotypes 10th annual meeting. Birmingham, United Kingdom, November 18-19, 1999. Abstracts. PMID- 11202902 TI - Arterial blood gas analysis during pulmonary artery catheterization: a comparison between two oxygen delivery systems. PMID- 11202903 TI - On the use of Venturi's principle to describe entrainment during jet ventilation. PMID- 11202904 TI - [Molecular classification of colorectal carcinoma]. PMID- 11202905 TI - Anaesthetic Research Society Meeting. Oxford, United Kingdom, July 6-7, 2000. Abstracts. PMID- 11202906 TI - The human polo-like kinase, PLK, regulates cdc2/cyclin B through phosphorylation and activation of the cdc25C phosphatase. AB - Entry into mitosis by mammalian cells is triggered by the activation of the cdc2/cyclin B holoenzyme. This is accomplished by the specific dephosphorylation of key residues by the cdc25C phosphatase. The polo-like kinases are a family of serine/threonine kinases which are also implicated in the control of mitotic events, but their exact regulatory mechanism is not known. Recently, a Xenopus homologue, PLX1, was reported to phosphorylate and activate cdc25, leading to activation of cdc2/cyclin B. Jurkat T leukemia cells were chemically arrested and used to verify that PLK protein expression and its phosphorylation state is regulated with respect to cell cycle phase (i.e., protein is undetectable at G1/S, accumulates at S phase and is modified at G2/M). Herein, we show for the first time that endogenous human PLK protein immunoprecipitated from the G2/M arrested Jurkat cells directly phosphorylates human cdc25C. In addition, we demonstrate that recombinant human (rh) PLK also phosphorylates rhcdc25C in a time- and concentration-dependent manner. Phosphorylation of endogenous cdc25C and recombinant cdc25C by PLK resulted in the activation of the phosphatase as assessed by dephosphorylation of cdc2/cyclin B. These data are the first to demonstrate that human PLK is capable of phosphorylating and positively regulating human cdc25C activity, allowing cdc25C to dephosphorylate inactive cdc2/cyclin B. As this event is required for cell cycle progression, we define at least one key regulatory mode of action for human PLK in the initiation of mitosis. PMID- 11202907 TI - Effect of elite cycling on leucocyte counts. PMID- 11202908 TI - Essential thrombocythaemia in children: a report of nine cases. PMID- 11202909 TI - All-trans retinoic acid (ATRA) and tranexamic acid: a potentially fatal combination in acute promyelocytic leukaemia. PMID- 11202911 TI - Repair of the nervous system. PMID- 11202910 TI - Aggressive multiple modality therapy for varicella-associated purpura fulminans. PMID- 11202912 TI - The future of pediatric education II. PMID- 11202913 TI - Relapses of CMV retinitis after 2 years of highly active antiretroviral therapy. PMID- 11202914 TI - A large rapidly growing pilomatrixoma on a lower eyelid. PMID- 11202915 TI - Use of mitomycin C and r-tPA for the management of conjunctival membrane and cataracts in a child with conjunctivitis lignosa. PMID- 11202916 TI - Annular granular corneal opacity: a rare corneal stromal dystrophy or degeneration? PMID- 11202917 TI - Idiopathic tractional corectopia. PMID- 11202918 TI - Subhyaloid or subinternal limiting membrane haemorrhage in meningococcal meningitis. PMID- 11202919 TI - Reverse and converse ocular bobbing with synkinetic blinking and opsoclonus in a child with Epstein-Barr virus encephalitis after bone marrow transplant for MPS I. PMID- 11202920 TI - Retinorhexis in macular translocation. PMID- 11202921 TI - Acute retinal necrosis presenting with scleritis and raised intraocular pressure. PMID- 11202922 TI - International Poverty and Health Network. PMID- 11202923 TI - Case 4: bronchiolitis obliterans in a lung transplant recipient. PMID- 11202924 TI - Interactive Grand Rounds. Case 3: management of cyclosporine-induced hirsutism and gingival overgrowth in a heart transplant recipient. PMID- 11202926 TI - Evaluation of laparoscopic procedures in the treatment of biliary disease, gastro oesophageal reflux and inguinal hernia. Proceedings of a conference. Sweden, 1997. PMID- 11202925 TI - Proceedings of the 7th International Course on Peritoneal Dialysis. Vicenza, Italy, May 23-26, 2000. PMID- 11202927 TI - Diagnosis: progressive multifocal leukoencephalopathy. PMID- 11202928 TI - [Status of the application of indicators to prove the effects of health education in local areas: analysis of research presentation of studies on adult and geriatric health at the meetings of the Japanese Public Health Association]. PMID- 11202929 TI - Implications of CJD data need to be clear before release. PMID- 11202930 TI - Effect of on-site mental health professionals. Longer trials are needed. PMID- 11202931 TI - Treating hyperhidrosis. Iontophoresis should be tried before other treatments. PMID- 11202932 TI - Treating hyperhidrosis. Excision of axillary tissue may be more effective. PMID- 11202933 TI - Treating hyperhidrosis. Anticholinergic drugs were not mentioned. PMID- 11202934 TI - Treating hyperhidrosis. Treatment options must be balanced against each other. PMID- 11202935 TI - Quality of randomised controlled trials in head injury. More trials are needed. PMID- 11202936 TI - Quality of randomised controlled trials in head injury. Statistical power can be increased. PMID- 11202937 TI - Transfusion transmitted infection. Did authors systematically underestimate risks of transfusion? PMID- 11202938 TI - National service framework's financial implications are huge. PMID- 11202939 TI - Advance directives. Three questions should be asked. PMID- 11202940 TI - Advance directives. Maybe national guidelines are needed. PMID- 11202941 TI - Advance directives. Legal issues need clarification. PMID- 11202942 TI - Advance directives. Advance directives are not legally binding. PMID- 11202943 TI - Advance directives. Good education prepares people for death. PMID- 11202944 TI - Role of spironolactone in heart failure should be emphasised. PMID- 11202945 TI - Patient of gynaecologist who was struck off has been denied justice. PMID- 11202946 TI - UK and German media differ over complementary medicine. PMID- 11202947 TI - Nestle's violation of international marketing code. The auditors respond. PMID- 11202948 TI - Nestles violation of international marketing code. Nestle responds. PMID- 11202949 TI - Nestle's violation of international marketing code. Audit report fudges the issue. PMID- 11202950 TI - Nestle's violation of international marketing code. Similar practices take place in Europe. PMID- 11202951 TI - Unicef and baby food manufacturers. Unicef continues to base its actions and programmes on the best interests of the child. PMID- 11202952 TI - Unicef and baby food manufacturers. Compliance to the code is difficult to judge. PMID- 11202953 TI - Comparing health inequality in men and women. Choice of indicator is important. PMID- 11202954 TI - Towards explaining health inequalities. PMID- 11202955 TI - Sterilise in haste, repent at leisure and great expense. PMID- 11202956 TI - Breast feeding is a major factor in HIV transmission. PMID- 11202957 TI - HIV/AIDS programmes should focus on improved access. PMID- 11202958 TI - 'Know thy cell!' a comment on the UKCCCR guidelines for the use of cell lines. PMID- 11202960 TI - Annual conference of the Canadian Society of Transfusion Medicine (CSTM). Quebec City, 4-7 May 2000. Abstracts. PMID- 11202959 TI - Management of complicated and treatment-refractory ED: clinical issues and guidelines. PMID- 11202961 TI - 13th International Congress of the Hungarian Society for Microbiology. August 29 September 1, 1999. Budapest, Hungary. Abstracts. PMID- 11202962 TI - The outcome of endoluminal repair of AAA with short proximal necks. PMID- 11202963 TI - Gene therapy to prevent vein graft stenosis--ready for prime time? PMID- 11202964 TI - For debate: concomitant critical coronary arterial disease and abdominal aortic aneurysm--timing of corrective procedures. AB - BACKGROUND: The high prevalence of coronary artery disease (CAD) in patients with abdominal aortic aneurysm (AAA) is responsible for most , 30-day mortality and morbidity in elective repair of AAA. The continuing debate regarding staged or combined surgery for AAA and CAD (coronary artery bypass grafting -CABG) in the small number of patients with critical degrees of both co-morbidities has not had a significant impact on the greater mortality and morbidity when the AAA repair is undertaken using the standard open operation. PATIENTS: We report four cases with these combined pathologies which we have managed over the last 30 months during which time we have developed techniques of endolumenal repair of AAA. CONCLUSIONS: Whilst it is not possible to make firm recommendations regarding management strategy owing mainly to a lack of large series reporting this unusual combination of co-morbidities, the options are debated on the basis of published anecdotal evidence as well as our own case reports. We suggest that if the AAA is non-tender and/or 5.5-8.0 cm, the staged approach is appropriate. If the AAA is tender and/or > 8.0 cm, a combined approach may be a better option in order to avoid the risk of AAA rupture during the interval between the operations. Endolumenal repair of AAA offers a further option for the staged and combined approach, and may be less invasive than the standard open surgery for AAA repair. PMID- 11202965 TI - Colorectal cancer. Preface. PMID- 11202966 TI - Pharmacological therapy of spinal cord injury during the acute phase. PMID- 11202967 TI - Caspases and neurodegenerative diseases. PMID- 11202968 TI - Clinical gene therapy back in the race. PMID- 11202969 TI - Knocking out NEMO. PMID- 11202970 TI - New imaging techniques for early diagnosis of Alzheimer's disease. PMID- 11202971 TI - Is successful gene therapy for retinal disease in sight? PMID- 11202972 TI - Molecular signalling in cardiovascular biology: from molecules to man. International symposium organized by the centre for cardiovascular biology and medicine, King's College, London. PMID- 11202973 TI - Have tumor cells learnt from microorganisms how to fool the immune system? Escape from immune surveillance of tumors and microorganisms: emerging mechanisms and shared strategies. PMID- 11202974 TI - Fecal colonization with vancomycin-resistant enterococci in Australia. AB - To assess the rate of fecal vancomycin-resistant enterococci (VRE) colon ization in Austalia, we examined specimens from 1,085 healthy volunteers. VRE was cultured from 2(0.2%) of 1,085 specimens; both were vanB Enter ococcus faecium, identical by pulsed-field gel electrophoresis, but with a pattern rare in Melbourne hospitals. PMID- 11202975 TI - Proceedings of the 12th International Symposium on Pediatric Surgical Research. Brussels, Belgium, September 3-4, 1999. PMID- 11202976 TI - Endemic instability for babesiosis and anaplasmosis in cattle in the Bolivian Chaco. PMID- 11202977 TI - Whither poultry disease and research? PMID- 11202979 TI - 22nd congress of the European Society of Cardiology, Amsterdam. PMID- 11202978 TI - Peripheral ameloblastic fibroma. PMID- 11202980 TI - 5th World Congress of the International Federation for the Surgery of Obesity. Genoa, Italy, September 20-23. Abstracts. PMID- 11202981 TI - Guidelines for laparoscopic and open surgical treatment of morbid obesity. American Society for Bariatric Surgery. Society of American Gastrointestinal Endoscopic Surgeons. PMID- 11202982 TI - Evolving Fontan strategy: hemi-Fontan procedure and its clinical application. PMID- 11202983 TI - Palliative therapy. Introduction. PMID- 11202984 TI - Orchestrating cell division. PMID- 11202985 TI - Mechanisms of joint destruction in rheumatoid arthritis. PMID- 11202986 TI - Bcl-2 does not inhibit cell death induced by the physiological Fas ligand: implications for the existence of type I and type II cells. PMID- 11202987 TI - Catheter ablation for atrial fibrillation and atrial flutter: from D.C. shocks to radiofrequency current. PMID- 11202989 TI - Comments on Serger et al.'s (1998, 1999) calorimetric stability studies. PMID- 11202988 TI - Proniosomes: a novel drug carrier preparation. AB - A procedure is described for producing a dry product which may be hydrated immediately before use to yield aqueous niosome dispersions similar to those produced by more cumbersome conventional methods. These 'proniosomes' minimize problems of niosome physical stability such as aggregation, fusion and leaking, and provide additional convenience in transportation, distribution, storage, and dosing. This report describes the preparation of dispersions of proniosome derived niosomes, comparison of these niosomes to conventional niosomes, and optimization of proniosome formulations. In addition, conventional and proniosome derived niosomes are compared in terms of their morphology, particle size, particle size distribution, and drug release performance in synthetic gastric or intestinal fluid. In all comparisons, proniosome-derived niosomes are as good or better than conventional niosomes. PMID- 11202990 TI - Current trends in toxicological risk assessment: perspectives from the committee on toxicology. PMID- 11202991 TI - Recent developments in neurotoxicology. PMID- 11202992 TI - Immunotoxicology: past, present, and future. PMID- 11202993 TI - Recent advances in reproductive and developmental toxicology. PMID- 11202994 TI - The use of transgenic animals in cancer testing. PMID- 11202995 TI - Recent developments in toxicology training. PMID- 11202996 TI - Mechanistic considerations in cancer risk assessment. PMID- 11202997 TI - Recent advances in genetic toxicology and their relevance to cancer risk assessment. PMID- 11202998 TI - Biologically based dose-response models for developmental toxicants: lessons from methylmercury. PMID- 11202999 TI - A unified approach to risk characterization. PMID- 11203000 TI - Benchmark doses for developmental toxicants. PMID- 11203001 TI - Epidemiologic approaches to risk assessment. PMID- 11203002 TI - Addressing uncertainty-lessons from probabilistic exposure analysis. PMID- 11203003 TI - The rise of exposure assessment among the risk sciences: an evaluation through case studies. PMID- 11203004 TI - Exposure analysis and assessment in the 21st century. PMID- 11203005 TI - Re: revisiting epidemiological key studies on occupational diesel exhaust exposure and lung cancer in truck drivers. PMID- 11203006 TI - Re: revisiting epidemiological key studies on occupational diesel exhaust exposure and lung cancer in truck drivers. PMID- 11203007 TI - Room temperature stable polymerase chain reaction mixture for detection of hepatitis B virus. PMID- 11203008 TI - Optimal therapeutic management of non-Q-wave myocardial infarction. PMID- 11203009 TI - Analysis of risk factors for the development of late hepatic artery thrombosis: do CREG mismatches play a role? PMID- 11203010 TI - Enteral feeding maintains but does not improve villous atrophy in malnourished patients. PMID- 11203011 TI - Bladder cancer mortality with aging: male/female comparison with autocorrelation and time frame shift. PMID- 11203012 TI - Carbonic anhydrase inhibitors--Part 94. 1,3,4-thiadiazole-2 sulfonamidederivatives as antitumor agents? AB - Potent sulfonamide inhibitors of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), derivatives of I ,3,4-thiadiazole-2-sulfonamide, possessing inhibition constants in the range of 10(-8)-10(-9) M against isozymes II and IV, were shown to act as efficient in vitro tumour cell growth inhibitors with GI(50) (molarity of inhibitor producing a 50% inhibition of tumour cell growth) values typically in the range of 0.1-30 microM against several leukaemia, non-small cell lung cancer, ovarian, melanoma, colon, CNS, renal, prostate and breast cancer cell lines. The mechanism of antitumour action with the new sulfonamides reported here is unknown, but it might involve either inhibition of several CA isozymes (such as CA IX, CA XII, CA XIV) present predominantly in tumour cell membranes, acidification of the intracellular environment as a consequence of CA inhibition, uncoupling of mitochondria and/or strong CA V inhibition, or a combination of several such mechanisms. Such derivatives might lead to the development of effective novel types of anticancer agents/therapies. ? 2000 Editions scientifiques et m|dicales Elsevier SAS. PMID- 11203013 TI - [Can even prevention be wrong? On military consciousness in medicine]. PMID- 11203014 TI - Trends in child neuropsychology. PMID- 11203015 TI - Web Alert. PMID- 11203016 TI - Web alert. Internet guide to hypertension associations and publications. PMID- 11203017 TI - Web alert. Keeping up with medical news: daily health headlines on the Internet. PMID- 11203018 TI - Web alert. Clinical trials in hypertension: guides on the internet. PMID- 11203019 TI - We alert. Clinical hypertension guidelines on the web. PMID- 11203020 TI - Web alert. PMID- 11203021 TI - Web alert. PMID- 11203022 TI - Web alert. PMID- 11203023 TI - Lymphoid organogenesis. Proceedings of the workshop held at the Basel Institute for Immunology. 5-6 November 1999. PMID- 11203024 TI - [Comment on T. G. Lehmann et al.: Klippel-Trenaunay syndrome involving the rectum]. PMID- 11203025 TI - Quiz case. Ulcerative colitis? Crohn's disease? PMID- 11203027 TI - Primary and preventive care: periodic assessments. ACOG Committee on Primary Care. PMID- 11203026 TI - Gastric uptake of nicotinic acid by bilitranslocase. PMID- 11203028 TI - Oral contraceptives for adolescents: benefit and safety. PMID- 11203029 TI - Family medicine funding crisis: opportunities and dangers. 1984. PMID- 11203030 TI - Long-term effects of omeprazole on the gastric mucosa. PMID- 11203031 TI - Long-term omeprazole treatment and risk of gastric cancer. PMID- 11203032 TI - Efficacy and safety of long-term omeprazole treatment. PMID- 11203033 TI - Molecular mechanisms of glucocorticoid resistance. PMID- 11203034 TI - The white plaque represents gastric mucosal metastatic calcification, which stains as dark deposits in the submucosa. PMID- 11203035 TI - The MacArthur Foundation Depression Education Program for Primary Care Physicians: background and rationale. AB - In order to improve the assessment and management of depression in general medical care, the John D. and Catherine T. MacArthur Foundation supported the development, evaluation, and dissemination of an eight-hour depression education program (DEP) for primary care physicians. This publication includes a paper describing the background and educational rationale for the program structure, the complete participant's workbook, and a facilitator's guide for teaching the program. Given in two separate four-hour workshops by a psychiatrist and a primary care physician, DEP is delivered to small groups of learners (about 12) using an interactive adult learning model and multiple teaching techniques including targeted yet flexible objectives, two lectures, videotape demonstration and discussion, role-play exercises, a focused monograph on depression, an interview checklist, structured assessment and outcomes tools, clinical case studies, and audiotape review of actual patient interviews. DEP has been shown in a prospective randomized trial to improve physicians' interview-ing skills as well as simulated-patient satisfaction scores. Over 150 PCPs in four states have taken DEP in more than 30 separate programs given by 24 trained facilitators. Participants, despite a wide diversity of background knowledge and skills, have uniformly reported remarkably positive learner satisfaction with all dimensions of the Program. PMID- 11203037 TI - Haloperidol-induced impotence improved by switching to olanzapine. PMID- 11203036 TI - The use of intravenous valproate in acute mania. PMID- 11203038 TI - Fibres evidence, probabilistic evaluation and collaborative test. PMID- 11203039 TI - Proceedings of the 2nd National Workshop on Helicobacter pylori: Management recommendations in India. Thrissur, Kerala, February 20, 1999. PMID- 11203041 TI - ECG mimicking acute myocardial infarction during heart involvement by lung neoplasm. PMID- 11203040 TI - What is the cause of lymphopenia in malaria? PMID- 11203042 TI - Left ventriculo-coronary communications in a double-outlet right ventricle with an intact ventricular septum. PMID- 11203043 TI - Systolic and diastolic forward flow in the left ventricular outflow tract in a patient with familiar restrictive cardiomyopathy. PMID- 11203044 TI - Lipoprotein(a), tobacco use, and risk of coronary heart disease. PMID- 11203045 TI - Spontaneous coronary artery dissection in old woman treated with coronary artery bypass graft. PMID- 11203046 TI - Embolizing mobile thrombus associated with prolapse and mixoid degeneration of the mitral valve. PMID- 11203047 TI - National service framework heart failure. PMID- 11203048 TI - Methodological errors uncovered? PMID- 11203049 TI - Successful emergency coronary surgery for intractable ventricular fibrillation without prior angiography. PMID- 11203050 TI - Coronary stent occlusion following strenuous exertion: is the risk actual? Is it preventable? PMID- 11203051 TI - Torsades de pointes due to multihormonal deficiency induced long QT syndrome. PMID- 11203052 TI - The neglected subject of biophysics. PMID- 11203053 TI - [The war: a risk for public health]. PMID- 11203054 TI - [Consumption of drugs: policies and social pact]. PMID- 11203056 TI - Spring joint meeting of the BIPP Medical Photography Group, the Royal Photographic Society's Medical Group and the Institute of Medical Illustrators, Kodak House, Hemel Hempstead, UK, April 8, 2000. PMID- 11203055 TI - [Screening for breast cancer: scientific evidence and the media]. PMID- 11203057 TI - Analysis of excretory-secretory and somatic antigens of Gastrothylax crumenifer. AB - The excretory/secretory (ES) metabolic products released by Gastrothylax crumenifer (Trematoda: Digenea) during in vitro incubations and the somatic extract of the adult parasite were analysed using polyacrylamide gel electro phoresis (PAGE). Immunogenicity of ES and somatic extracts were evaluated by immunoblotting and ELISA using sera raised against ES and somatic antigens in rabbits. The electropherograms of ES and somatic extracts have been resolved into 38 and 41 polypeptides, respectively. The apparent molecular weights of these polypeptides range from <29 to > 205 kDa. A total of 14 polypeptides were found to be common to both of the samples. The analysis of immunoblot results revealed 22 and 27 antigenic polypeptides in ES and somatic extracts respectively. Only 11 and 13 antigenic polypeptides were found specific to ES and tissue extract respectively. The molecular weights of these specific polypeptides were calculated to be <14.4, 16, 20, 25, 33, 42, 119, 125 and > 205 kDa for metabolic products and <14.4, 25, 30, 35, 78, 84 and > 205 kDa for the tissue extracts, respectively. Analysis of ELISA results revealed that a dilution of up to 1:3200 of the test sera could react with the ES product. Further, when the ES antigens were allowed to react with antisomatic extracts in hyperimmune sera the titre of IgG increased up to a dilution of 1:12800. The potential importance of these antigens in the immunodiagnosis of amphistomiasis is discussed. PMID- 11203058 TI - The biology of depression. AB - Depression is a common psychiatric disorder prevalent in 10-15% in general population. To know the biology of the disease many hypotheses have been proposed. Genetic basis for depression is provided by family studies which show higher risk of depression among first degree relatives. Abnormalities in serotonergic activity in depression can occur in one or more levels. Other neurotransmitters like gamma amino butyric acid (GABA) and dopamine are also considered to have some role in depression. Hormonal abnormalities like hypercortisolaemia are found in patients with depression. Structural and functional neuro-imaging studies in depression suggest the involvement of brain in depressive disorders. PMID- 11203060 TI - 6th Conference of the Federation of Infection Societies. Manchester, United Kingdom, December 1-3, 1999. Abstracts. PMID- 11203059 TI - Mumfer (iron polymaltose complex) in the management of anaemia in pregnancy--an Indian study. PMID- 11203061 TI - Eclampsia and postpartal cerebral angiopathy. PMID- 11203062 TI - [Aspirin-induced asthma and nose diseases]. PMID- 11203063 TI - [Approach to a borderline area: sinobronchial syndrome]. PMID- 11203064 TI - 13th International Congress on Care of the Terminally Ill. September 25-29, 2000. Montreal, Canada. Abstracts. PMID- 11203065 TI - Regarding "The Swiss Heroin Trials: scientifically sound?". PMID- 11203066 TI - Regarding "The Swiss Heroin Trials: scientifically sound?". PMID- 11203067 TI - Regarding "The Swiss Heroin Trials: scientifically sound?". PMID- 11203068 TI - Regarding "The Swiss Heroin Trials: scientifically sound?". PMID- 11203069 TI - Regarding "The Swiss Heroin Trials: scientifically sound?". PMID- 11203071 TI - Re: Recognizing abnormal marker results that do not reflect disease in patients with germ cell tumors. PMID- 11203070 TI - Receptors for hepatitis C virus. PMID- 11203072 TI - Re: Periprostatic local anesthesia before ultrasound guided prostate biopsy. PMID- 11203073 TI - Re: A prospective study of the natural history of hematuria associated with benign prostatic hyperplasia and the effect of finasteride. PMID- 11203074 TI - Re: Complexed prostate specific antigen provides significant enhancement of specificity compared with total prostate specific antigen for detecting prostate cancer. PMID- 11203075 TI - Grading and staging of bladder carcinoma in transurethral resection specimens: correlation with 105 matched cystectomy specimens. PMID- 11203076 TI - Markers for recurrence of superficial bladder cancer: what is valid? PMID- 11203077 TI - Relationship between kidney size, renal injury, and renal impairment induced by shock wave lithotripsy. PMID- 11203078 TI - Routine radiologic surveillance for obstruction is not required in asymptomatic patients after ureteroscopy. PMID- 11203079 TI - Ureteropelvic junction obstruction: use of helical CT for preoperative assessment -comparison with intraarterial angiography. PMID- 11203080 TI - The 10th Clinical Cancer Research Forum. PMID- 11203081 TI - [Aleksandr Alekseevich Bobrov (the 150th anniversary of his birth)]. PMID- 11203082 TI - [Aleksandr Nikolaevich Bakulev (the 110th anniversary of his birth)]. PMID- 11203083 TI - [Walker-Warburg syndrome in adults]. PMID- 11203084 TI - [Pediatrics 2000 Conference. 14-17 September 2000. Stuttgart, Germany. Abstracts]. PMID- 11203085 TI - The AIDS epidemic: lessons learned? PMID- 11203086 TI - Competitiveness in science. Today, tomorrow and for ever. PMID- 11203087 TI - Competitiveness in science. Today, tomorrow and for ever. PMID- 11203088 TI - [Echinococcoses (hydatidoses) caused by Echinococcus multilocularis, E. vogeli and E. oligarthrus. Based on materials from the 19th International Congress on Hydatidology (San Carlos de Bariloche, Argentina, 20-24 September 1999)]. PMID- 11203089 TI - [Diagnostic and therapeutic criteria for nosocomial pneumonia]. PMID- 11203090 TI - Misinterpretation of DNA sequence data generated by polymerase chain reactions. PMID- 11203091 TI - Proceedings of the Oral Health Forum 2000: Improving the oral health of all New Zealanders. Palmerston North, New Zealand, 4-6 May 2000. PMID- 11203092 TI - Medical Research Ethics at the Millennium: What Have We Learned? Proceedings of a symposium. Bethesda, Maryland, USA. March 1998. PMID- 11203093 TI - Cancer resources in the United States. PMID- 11203094 TI - Deep vein thrombosis. PMID- 11203095 TI - Portals that shine. Not all physician Web portals are created equal. Here's a review of five leading sites and why they stand out. PMID- 11203096 TI - Will pay for email. PMID- 11203097 TI - Why are physicians still turning their backs on the Internet? PMID- 11203098 TI - The activities of bacterial pathogens in vivo. Papers of a discussion meeting. 20 21 October 1999. PMID- 11203099 TI - [37th Annual meeting of the Society for Pediatric Radiology. Freiburg. Abstracts]. PMID- 11203100 TI - What's that sound. PMID- 11203101 TI - Treating tobacco use and dependence: an introduction to the US Public Health Service Clinical Practice Guideline. PMID- 11203102 TI - Unusual ventilator graphics encountered following successful resuscitation from cardiac arrest. PMID- 11203103 TI - Consensus Conference on Aerosols and Delivery Devices. September 24-26, 1999, Bermuda. PMID- 11203104 TI - Considering quality of voice in early vocal cord carcinoma. PMID- 11203105 TI - Set-up error for conformal radiotherapy of prostate cancer. PMID- 11203106 TI - Microbial genomes 2000. Highlights from the American Society for Microbiology - Institute Pasteur Conference. Paris, France, April 11-15, 2000. PMID- 11203107 TI - [Prevention of the chronic complications of type 2 diabetes: A consensus from the Mexican Society of Nutrition and Endocrinology, the Mexican Association of Internal Medicine, and the Society of Nutriology]. PMID- 11203108 TI - Diagnosis and treatment of sleep breathing disorders. Proceedings of a symposium. Grenoble, France, December 1998. PMID- 11203109 TI - [Obesitology '98. Selected papers presented at the conference organized by the Czech Society for the Study of Obesity and the J.E. Purkyne Medical Association held 23-24 October 1998 in Podebrady, Lazensky Dum]. PMID- 11203110 TI - [Environmental hygiene: current conditions and future perspectives. Conference proceedings. Berlin, 9-11 June 1999]. PMID- 11203111 TI - The challenge of fibromyalgia: new approaches. Proceedings from a symposium. Frankfurt, Neu-Isenburg, Germany. 25-26 November 1999. PMID- 11203112 TI - [Joint Congress of the Swiss Society of Rheumatology and the Swiss Society of Physical Therapy and Rehabilitation. Lucerne, 13-15 September 2000. Abstracts]. PMID- 11203113 TI - [Is the "dental team" still attractive?]. PMID- 11203114 TI - [The development of insolvency in Switzerland has become an existential threat]. PMID- 11203115 TI - [The last bill]. PMID- 11203116 TI - [Swiss dental fees are doing harm]. PMID- 11203117 TI - [Prof. Peter Scharer, M. S., emeritus]. PMID- 11203118 TI - [The identification of an unknown male corpse. Who recognizes this maxillary status?]. PMID- 11203119 TI - Biologist Paul R. Ehrlich. Six billion and counting. PMID- 11203120 TI - [Factors affecting prognosis in penetrating wounds of the heart]. PMID- 11203121 TI - Association between heritable connective tissue disorders and intracranial aneurysms. PMID- 11203122 TI - Thoughts about the younger generation. PMID- 11203123 TI - Cisternal irrigation with UK to prevent vasospasm. PMID- 11203124 TI - Spinal meningiomas. PMID- 11203125 TI - Transthoracic endoscopic sympathectomy. PMID- 11203126 TI - Paracetamol and asthma. PMID- 11203127 TI - Paracetamol and asthma. PMID- 11203128 TI - Paracetamol and asthma. PMID- 11203129 TI - Paracetamol and asthma. PMID- 11203130 TI - Paracetamol and asthma. PMID- 11203131 TI - Paracetamol and asthma. PMID- 11203132 TI - Paracetamol and asthma. PMID- 11203133 TI - Hyperventilation syndrome. PMID- 11203134 TI - Fibrin formation in whole blood. PMID- 11203135 TI - [Patents of the Russian Federation in the field of stomatology published in 1997 2000]. PMID- 11203136 TI - Which way is up? PMID- 11203137 TI - A plea to search for deletion polymorphism through genome scans in populations. PMID- 11203138 TI - How 'homology' entered genetics. PMID- 11203139 TI - Silencing survival data. PMID- 11203141 TI - [Recommendations by the teaching-methodology commission on otorhinolaryngology]. PMID- 11203140 TI - Un pour tous, tous pour un. PMID- 11203142 TI - [Dissertations defended in 2000]. PMID- 11203143 TI - International forum: granulocyte transfusions. PMID- 11203144 TI - Minocycline-induced generalized postinflammatory elastolysis. PMID- 11203145 TI - The effects of Ramadan fasting on blood lipid levels. PMID- 11203146 TI - Managed care and education. PMID- 11203147 TI - Do plasma melatonin concentrations decline with age? PMID- 11203148 TI - The Oslerian triple-threat: an endangered species? A survey of department of medicine chairs. PMID- 11203149 TI - [4th National Gynecological Conference. April 2000, Bulgaria. Abstracts]. PMID- 11203150 TI - Iron deficiency anaemia, Helicobacter pylori infection and delayed pubertal growth. PMID- 11203151 TI - Iron status and development. PMID- 11203152 TI - Coeliac screening just as important! PMID- 11203153 TI - Consider absolute risks in SIDS prevention. PMID- 11203154 TI - Are we requesting too many DMSA scans? PMID- 11203155 TI - From wheels to feet: a dramatic response of severe chronic psoriatic arthritis to etanercept. PMID- 11203156 TI - Polymyositis, cranial neuropathy, autoimmune hepatitis, and hepatitis C. PMID- 11203157 TI - Apolipoprotein B signal peptide polymorphism in relation to lipids and diabetes in male CAD patients. PMID- 11203158 TI - Lipoprotein (a) and chronic obstructive pulmonary disease. PMID- 11203159 TI - Relationship between plasma ACE activity and the proliferative healing process in coronary vessel injury after coronary stenting. PMID- 11203160 TI - The carotid artery wall thickness in teenagers is related to their diet and the typical risk factors of heart disease among adults. PMID- 11203161 TI - Intranasal midazolam and familial dysautonomia. PMID- 11203162 TI - Simple and economic workstation for burn intensive care. PMID- 11203163 TI - Barriers to screening for intimate partner violence: time to reframe the question. PMID- 11203164 TI - Criminal justice responses to violence against women. PMID- 11203165 TI - Violence against women: international perspectives. PMID- 11203166 TI - Cover illustration: The original slit beam. PMID- 11203167 TI - Sudden bilateral visual loss in acute myeloid leukemia. PMID- 11203168 TI - Serous retinal detachment caused by leukemic choroidal infiltration during complete remission. PMID- 11203169 TI - Diplopia, ptosis, and hepatitis as presenting signs and symptoms of giant cell arteritis. PMID- 11203170 TI - Observations on time course changes of the cherry red spot in a patient with Tay Sachs disease. PMID- 11203171 TI - Effects of homozygous apolipoprotein A-1 deficiency on the cornea. PMID- 11203172 TI - Acquired capillary haemangioma of the eyelid in an adult treated with cutting diathermy. PMID- 11203173 TI - Idiopathic sclerosing inflammation of the orbit: a new finding of calcification. PMID- 11203174 TI - Therapy of subhyaloidal hemorrhage by intravitreal application of rtPA and SF(6) gas. PMID- 11203175 TI - Sebaceous gland carcinoma of the eyelid and palpebral conjunctiva in a patient with Muir-Torre syndrome. PMID- 11203176 TI - Ophthlamic features of primary oxalosis after combined liver/kidney transplantation. PMID- 11203177 TI - Retinal telangiectasis and angioid streaks. PMID- 11203178 TI - Sclerosing lipid granuloma of the medial canthus 30 years after dacryocystitis. PMID- 11203179 TI - Treatment of subhyaloid haemorrhage with intravitreal tissue plasminogen activator and C3F8 gas injection. PMID- 11203180 TI - Blunt trauma in Best's vitelliform macular dystrophy. PMID- 11203181 TI - Epidermoid carcinoma arising in an ocular Leishmania lesion. PMID- 11203182 TI - [Exudative retinal detachment in a clinical case]. PMID- 11203183 TI - Paroxetine binding to the rat norepinephrine transporter in vivo. PMID- 11203184 TI - Photo quiz. Diagnosis: hydatid bone disease (cystic echinococcosis). PMID- 11203185 TI - Proceedings of the 2nd Joint Workshop on Cytokines in Inflammation. Lubeck, Germany, May 11-14, 2000. PMID- 11203186 TI - Interleukin-18, a proinflammatory cytokine. AB - Although IL-18 is an inducer of IFN-gamma and Th1 responses. IL-18 is a proinflammatory cytokine by several criteria. In several animal models. antibodies that neutralize endogenous IL-18 reduce the severity of disease. Endotoxin lethality is prevented by anti-IL-18. Even in models that are interferon-y independent, neutralization of IL-18 prolongs survival. Anti-IL-18 also protects the liver against cellular injury induced by toxins or activated T cells. In models of hepatic melanoma metastasis. IL-18 blockade reduces the adherence of malignant cells by preventing IL-18 upregulation of vascular endothelial adhesion-1 molecule expression. IL-18 and IL-12 act synergistically to stimulate I cells and natural killer cells to produce IFN-gamma but neutralization of IL-18 prevents IL-12 induction of IFN-gamma. IL-18. like several cytokines. can be used to enhance host defense against tumors in mice a mechanism that is most often IFN-gamma-dependent. Nevertheless. it is the proinflammatory portfolio of IL-18 which likely contributes to enhanced host defenses. In models or arthritis, lung injury or inflammatory bowel disease, neutralization of IL-18 reveals the important role of this cytokine in mediating inflammation. PMID- 11203187 TI - GD3 ganglioside as an intracellular mediator of apoptosis. PMID- 11203188 TI - Toll like receptor family (TLT) and signalling pathway. PMID- 11203189 TI - Signalling of interleukin-6 type cytokines via gp130, leukemia inhibitory factor (LIF) receptor and oncostatin M receptor. PMID- 11203190 TI - Integrin-mediated regulation of cytokine and chemokine production by human natural killer cells. PMID- 11203191 TI - Chemokines and their receptors: trafficking cues for Th1 and Th2 cells. PMID- 11203192 TI - Regulation of cytokine transcription by common stress kinase cascades. PMID- 11203193 TI - NRF, a nuclear inhibitor of NF-kappaB proteins silencing interferon-beta promoter. AB - The family of NF-kappaB/rel transcription factors regulates a variety of promoters through specific DNA-binding sites. Consistent with the role of NF kappaB activation as a response to pathogens, it regulates the expression of immune modulating cytokines like interferon-beta3 (IFN-3). Transcriptional regulation of IFN-beta is characterized by strict constitutive repression and virus-mediated activation. A nuclear protein, called NRF (NF-kappaB repressing factor) silences constitutively the IFN-beta3 promoter by binding to the negative regulatory element (NRE). This control is achieved by a direct protein-protein interaction between NRF and proximal bound NF-kappaB factors preventing the transcriptional activation. After viral induction NRF still binds but does not any more exert its specific inhibition. NRE-related sequences found in a number of promoters like those of HIV-1, HTLV-1 and the genes of the IL-2Ralpha and IL-8 constitute functionally related silencer elements which repress the constitutive enhancing activity of NF-kappaB/rel-binding sites from these promoters. PMID- 11203194 TI - In vitro and in vivo regulation of chemokine receptors. PMID- 11203195 TI - Functional organization of secondary lymphoid organs by homeostatic chemokines. PMID- 11203196 TI - Is platelet factor-4 a chemokine? PMID- 11203197 TI - Inhibition of dendritic cell costimulation associated with tolerance to allografts. PMID- 11203198 TI - Th1/Th2 cells, their associated molecules and role in pathophysiology. AB - Cytokines, chemokines, and/or chemokine receptors associated with type 1 T helper (Th1) or Th2 cells play a role in different physiological conditions, such as T lymphopoiesis and pregnancy, as well as in pathological conditions, such as unexplained recurrent abortions, proliferative glomerulonephritis, and control of angiogenesis. PMID- 11203199 TI - Modulation and termination of interleukin-6 signalling. PMID- 11203200 TI - Morphogenic and host protective functions executed by tumor necrosis factor receptors, lymphotoxin receptors and their ligands. PMID- 11203201 TI - IL-18 and IL-18 receptors in the development of autoimmunity. PMID- 11203202 TI - Different biological role and anti-tumor activity of interleukin-15 isoforms. PMID- 11203203 TI - No RISC, no fun: assembly of receptor-induced signalling complexes in the tumor necrosis factor system. PMID- 11203204 TI - Inhibiting the IL-4 receptor: why, how, and for whom? PMID- 11203205 TI - The ABL kinase inhibitor STI571 does not affect survival of hematopoietic cells after ionizing radiation. PMID- 11203206 TI - Hyperprothrombinemia may result in scquired activated protein C reistance. PMID- 11203207 TI - Private finance scheme for Worcester. Battle in Kidderminster is against "spin," half truth, and obfuscation. PMID- 11203208 TI - Meta-analysis of increased inhaled steroid or addition of salmeterol in asthma. Researchers can learn from industry based reporting standards. PMID- 11203209 TI - Babies sleeping with parents and sudden infant death syndrome. Smoking may be residual confounder in bed sharing. PMID- 11203210 TI - Babies sleeping with parents and sudden infant death syndrome. Down with smoking and babies sleeping in separate rooms. PMID- 11203211 TI - Second editorial on GMC is ironic. PMID- 11203212 TI - Isolated systolic hypertension. Is it time for me to retire from medicine? PMID- 11203213 TI - Upward trend in acute anaphylaxis continued in 1998-9. PMID- 11203214 TI - Provision of age appropriate health services for young people has been ignored. PMID- 11203215 TI - Emergence of multidrug resistant pneumococci in India. PMID- 11203216 TI - Incidence and remission of lower urinary tract symptoms. Results have practical implications. PMID- 11203217 TI - General medical journals should have covered war in Kosovo more. PMID- 11203218 TI - NICE issues new guidelines on Ritalin. PMID- 11203219 TI - Thabo Mbeki's spokesman "dies of aids related disease". PMID- 11203220 TI - Threat of chemical and germ attacks overstated, report says. PMID- 11203221 TI - No compensation for hepatitis C patients in Scotland. PMID- 11203222 TI - Anticoagulation to prevent stroke in atrial fibrillation. It's still not clear whether results in secondary care translate to primary care. PMID- 11203223 TI - Anticoagulation to prevent stroke in atrial fibrillation. Cohort was younger than many patients with atrial fibrillation in primary care. PMID- 11203224 TI - General practitioners have to decide best ways of allocating their time. PMID- 11203225 TI - Anticoagulation to prevent stroke in atrial fibrillation. Comprehensive geriatric evaluation should be routine before treatment is started. PMID- 11203226 TI - Standard definition of child overweight and obesity worldwide. Authors' standard compares well with WHO standard. PMID- 11203227 TI - Standard definition of child overweight and obesity worldwide. Young Chinese people in Hong Kong are not representative of those in China. PMID- 11203228 TI - Standard definition of child overweight and obesity worldwide. Body mass index is harder to interpret in children than adults. PMID- 11203229 TI - Standard definition of child overweight and obesity worldwide. Reanalysis suggests questionable validity of new definition during puberty. PMID- 11203231 TI - 8th International Conference on Emergency Medicine. Boston, Massachusetts, USA. 4 7 May 2000. Abstracts. PMID- 11203230 TI - Proceedings of the 2nd International Symposium on Transplantation and Gene Therapy. October 21-23, 1999. Idar-Oberstein, Germany. PMID- 11203232 TI - The generation of diversity by Haemophilus influenzae: response. PMID- 11203233 TI - The mycobacterial antigens 85 complex--from structure to function: response. PMID- 11203234 TI - Gram-negative pathogens and molecular mimicry: is there a case for mistaken identity? Response. PMID- 11203235 TI - PII: a remarkable regulatory protein. PMID- 11203236 TI - A mitochondrial origin for eukaryotic C2H2 zinc finger regulators? PMID- 11203237 TI - Significant Achievement Award. A model prison diversion program--The Criminal Justice-Community Outreach Department of the Montgomery County Emergency Service, Norristown, Pennsylvania. PMID- 11203238 TI - Significant Achievement Award. A rehabilitation program for inpatients in a large institution--The Psychosocial Rehabilitation Program at Eastern State Hospital, Williamsburg, Virginia. PMID- 11203239 TI - SAMHSA announces advances in the treatment of adolescent marijuana users. PMID- 11203240 TI - New study examines Americans' changing attitudes about mental health and treatment from 1950-1996. PMID- 11203241 TI - Mechanical ventilation of the newborn. PMID- 11203242 TI - PTV: should it be patient triggered and patient terminated ventilation? PMID- 11203243 TI - To trigger or not to trigger? PMID- 11203244 TI - Patient triggered ventilation. PMID- 11203245 TI - [The 2nd Symposium on The characteristics of the formation and development of psychophysiological functions in ontogeny (Cherkassy, 26-29 October 1999)]. PMID- 11203246 TI - "A simple country doctor": remembering Dr. Clare Brant. PMID- 11203247 TI - Variation within global cigarette brands in tar, nicotine, and certain nitrosamines: analytic study. PMID- 11203248 TI - Carbon monoxide in the expired air of smokers who smoke so-called "light" brands of cigarettes. PMID- 11203249 TI - Call-in for kids. PMID- 11203250 TI - New cytogenetic data on bladder carcinoma cell line (CHA89) revealed by M-FISH analysis. PMID- 11203251 TI - Translocation (5;18) in a patient with myelodysplastic syndrome: refractory anemia with excess blasts in transformation. PMID- 11203252 TI - Good publication practice guideline for pharmaceutical companies. PMID- 11203253 TI - [Toast proposed by professor Wlodzimierz Sieradzki to Ignacy Paderewski]. PMID- 11203254 TI - New millennium: new expectations for Alzheimer's disease? PMID- 11203255 TI - Immunohistochemical investigation of new suppressor oncogene p130 in oral squamous cell carcinoma, vol.35 (1999), 321-325. PMID- 11203256 TI - [Letter of Public Health Care Ministry of The Russian Federation of Jan. 31, 2000 on "Inpatient Clinics for Involuntary Commitment of Mentally Ill"]. PMID- 11203257 TI - [The pathology of epiconus medullaris. 1904]. PMID- 11203258 TI - [On the training of clinical psychologists and teaching psychology in institutes of higher learning in Russia]. PMID- 11203259 TI - [The role of S. S. Korsakov in the development of the Moscow psychiatric school]. PMID- 11203260 TI - [Nikolai Vasil'evich Konovalov (on the centenary of his birth)]. PMID- 11203261 TI - [The statement of the DGKfo on the optimal timing for the performance of orthodontic measures (with special reference to early orthodontic treatment). Deutsche Gesellschaft fur Kieferorthopadie (German Society of Orthodontics)]. PMID- 11203262 TI - The church of Sv. Spas (St. Savoir). PMID- 11203263 TI - Proceedings of the 4th International Symposium on Febrile Neutropenia. December 15-17, 1999. PMID- 11203264 TI - [Nuclear medicine in Latin America]. PMID- 11203265 TI - [Scintigraphy with FDG-PET]. PMID- 11203266 TI - The story of "story". PMID- 11203267 TI - The story of "story". PMID- 11203268 TI - Can "fighting spirit" be learned and chosen? PMID- 11203269 TI - Unexpected bleeding disorders: identification, diagnosis and management. PMID- 11203270 TI - Bioavailability of ibuprofen from matrix mini-tablets based on a mixture of starch and microcrystalline wax. AB - The bioavailability of ibuprofen from matrix mini-tablets based on microcrystalline wax and a starch derivative was tested. An oral dose of 300 mg of ibuprofen was administered to healthy volunteers (n=8) in a randomized cross over study design either as a commercial matrix formulation (Ibu-Slow 600) or as mini-tablets (filled into hard gelatin capsules). The mini-tablets consisted of 60% ibuprofen, 15% Paracera M (wax), 22.5% DDWM (starch) and 2.5% triacetin (lubricant). t50% of the in vitro release was 4.5 and 5 h for the mini-tablet and Ibu-slow formulations, respectively. Both formulations behaved in vivo as sustained-release formulation; their HVDt50%Cmax value was determined at 5.6 and 5.1 h for the mini-tablet and Ibu-slow formulations, respectively. A significantly higher value of Cmax was seen for the mini-tablet formulation, resulting in a relative bioavailability of 116 +/- 22.6% compared to the Ibu-slow matrix. These data demonstrate that the experimental mini-tablets can be used to formulate sustained-release dosage forms. PMID- 11203271 TI - The dissolution of urinary catheter encrustation. PMID- 11203272 TI - Notice of duplicate publication. PMID- 11203273 TI - USAN Council. List No. 432. New Names. Alefacept, darbepoetin alfa, daclizumab. PMID- 11203274 TI - Molecular genetics of model legumes. PMID- 11203275 TI - ABI3 emerges from the seed. PMID- 11203276 TI - Microfibril orientation in wood cells: new angles on an old topic. PMID- 11203277 TI - Viral sequences integrated into plant genomes. PMID- 11203278 TI - BRInging light to hormone receptor activation. PMID- 11203280 TI - ENAMEL VI. Proceedings of the 6th international symposium on the composition, properties and fundamental structure of tooth enamel. Lake Arrowhead, California, USA. May 11-15, 1997. PMID- 11203279 TI - ORCAstrating plant primary and secondary metabolism. PMID- 11203281 TI - ENAMEL VI. Proceedings of the 6th International Symposium on the composition, properties and fundamental structure of tooth enamel. Lake Arrowhead, California, USA. May 11-15, 1997. PMID- 11203282 TI - Web alert. PMID- 11203283 TI - Web alert. PMID- 11203284 TI - Web alert. PMID- 11203286 TI - Web alert. PMID- 11203285 TI - Web alert. PMID- 11203287 TI - Ventricular tachycardia catheter ablation in arrhythmogenic right ventricular dysplasia: a 16-year experience. AB - Arrhythmogenic right ventricular dysplasia (ARVD) is a structural heart disease affecting young adults that leads to cardiac rhythm disorders including supraventricular and mostly ventricular arrhythmias. Sudden death may be the first presentation of the disease. Ablation techniques have been used for the treatment of ventricular tachycardia in cases resistant to drug therapy. Radiofrequency is appropriate as a first approach for ventricular tachycardia ablation in ARVD; however, its effectiveness is less than 40% at the first session. Fulguration is effective for ventricular tachy-cardia ablation and should be used in the same session after ineffective radiofrequency ablation. However, fulguration requires expertise, general anesthesia, and more than one session in half of all patients. Radiofrequency and fulguration plus other common forms of treatment including pacemakers and automatic implantable cardioverter defibrillators provides a clinical success rate of 81% to 93% in a series of 50 consecutive patients studied during 16 years. Earlier poor reputation of fulguration was the result of poorly understood technical problems concerning the physics and biophysics of the procedure under control with presently available methods. This in-depth study of a large population over a long time period demonstrates that fulguration should be rehabilitated. PMID- 11203288 TI - Biology, chemistry and therapeutic applications of nitric oxide: First International Conference. PMID- 11203289 TI - 18th Scientific meeting of the International Society of Hypertension. PMID- 11203290 TI - William Harvey Research Conference on PDE inhibitors: drugs with an expanding range of therapeutic uses. AB - Presentations at the William Harvey Research Conference on PDE Inhibitors described the molecular biology, biochemical regulation. pharmacology, and therapeutic utility of inhibitors of cyclic nucleotide phosphodiesterases (PDEs). Most of the talks focused on PDE4 and PDE5. two members of the 11-member PDE family that have attracted much interest over the last several years. These enzymes have been shown to be targets for drugs with wide-ranging clinical utility, including treatment of inflammation, depression, and male erectile dysfunction. The continued investigation of PDEs and the development of potent and selective inhibitors should provide even more therapeutic agents in years to come. PMID- 11203291 TI - Chemokines and chemokine receptors: disease targets for therapeutic development. November 15-16, 1999, McLean, VA, USA. AB - About a decade after discovery of IL-8, the first designated member of the protein family of chemotactic cytokines, about 50 of these so called 'chemokines' and about 15 receptors have been discovered in humans. Experimental as well as clinical data have identified many of the players in this network to be associated with various pathological phenomena. This conference discussed how research is closing in on chemokines as therapeutic targets as well as how chemokine functions might be exploited to design useful therapeutic tools. PMID- 11203292 TI - AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. AB - The pace of anticancer drug discovery and development has accelerated over recent years based upon a better understanding of tumour biology at the molecular level. Modern drug development has moved from empiricism to rational design and this was the theme of the inaugural meeting of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics held in Washington DC, November 16 - 19.1999. This was an excellent meeting where state of the art research in the areas of drug discovery, development and clinical evaluation of new cancer therapeutics was presented. A few of the highlights of this meeting are presented in this article but further details can he found in a supplement to Clinical Cancer Research (1999) 5:3729-3897, where all abstracts accepted for the meeting are published. This meeting is set to become the premier meeting for scientists and clinicians involved in all aspects of anticancer drug development (i.e., from bench to the bedside) and the next meeting will take place in Amsterdam on November 7-10, 2000. PMID- 11203293 TI - A rational basis for antiphospholipid antibody testing and selective immunotherapy in assisted reproduction: a rebuttal to the American Society for Reproductive Medicine Practice opinion. American Society for Reproductive Immunology Antiphospholipid Antibody Committee. PMID- 11203294 TI - Infrared thermographic assessment of the human scrotum. PMID- 11203295 TI - Luteal support in IVF using the novel vaginal progesterone gel Crinone 8%: results of an open-label trial in 1184 women from 16 US centers. PMID- 11203296 TI - Bone mineral density and Turner's syndrome--any lessons to be learned about "Menopausal Osteoporosis'. PMID- 11203297 TI - Bone mineral density and Turner's Syndrome--any lessons to be learned about "Menopausal Osteoporosis". PMID- 11203298 TI - Endometriomas: fenestration or excision? PMID- 11203299 TI - Antiphospholipid antibody status and IVF--debate. PMID- 11203300 TI - The value of laboratory accreditation. PMID- 11203302 TI - Parkinson's disease and other movement disorders 2000. Pavia, Italy, May 28-30, 2000. Abstracts. PMID- 11203301 TI - Expression of an estrogen receptor alpha variant protein in cell lines and tumors. AB - Human estrogen receptor alpha (ER) mRNA is a mixture of wild type and alternatively spliced variants. Many studies have examined the potential of ER mRNA profiles to serve as diagnostic/prognostic cancer biomarkers, but only a few have attempted to correlate ER mRNA profiles with protein expression. Representative ER mRNA pools were reproduced from the cDNAs of MCF-7 cells, a human breast tumor and human uterus and translated in a protease-free environment by reticulocyte lysates to determine relative translation efficiencies between the various ER mRNA transcripts and to facilitate identification of translated proteins. Cell line and tumor extracts were then examined for expression of the ER variant proteins identified in reticulocyte lysate translations. Each of the ER mRNA pools were translated by reticulocyte lysates into two ER proteins with molecular weights of approximately 60 and 52 kD. Western immunoblotting with various C- and N-terminal-directed, anti-ER antibodies and comparison with expressed ER protein standards established that the 52 kD protein (ERDelta7P) was translated from the predominant splice variant mRNA in each pool, which is missing exon 7. The 60 kD protein contained wild type ER sequence minus 61 C terminal amino acids lost due to an intentional run off truncation. ERDelta7P expression was subsequently demonstrated in MCF-7 cells by Western immunoblotting with the site-directed antibodies. A protein corresponding to ERDelta7P was also detected in other ER positive breast tumor cell lines, and extracts of ER positive breast and uterine tumors. This widespread expression of ERDelta7P in vivo suggests that it may have some biological function. ERDelta7P may also affect immunohistochemical evaluation of ER positivity in tumors depending upon the level of its expression and the antibody used. PMID- 11203303 TI - Liver disease and pulmonary hypertension. PMID- 11203304 TI - UDCA, PBC, and biochemistry, what does normal mean? PMID- 11203306 TI - Losartan and renal sodium handling. PMID- 11203305 TI - Endoscopic gastrin test and Helicobacter pylori infection. PMID- 11203307 TI - Replication error phenotype in colorectal cancer. PMID- 11203308 TI - Fibrosing colonopathy in an adult caused by over use of pancreatic enzyme supplements. PMID- 11203309 TI - Coeliac disease and unfavourable outcome of pregnancy. PMID- 11203310 TI - Hepatitis E acquired in the UK. PMID- 11203311 TI - Acid suppression and upper GI cancer diagnosis. PMID- 11203312 TI - Re-epithelialisation of Barrett's oesophagus. PMID- 11203313 TI - Outcome of lamivudine resistant hepatitis B virus infection in liver transplant recipients in Singapore. PMID- 11203314 TI - Gastric cancer in patients with benign dyspepsia. PMID- 11203315 TI - [Harry Gordon (1906-1988)]. PMID- 11203316 TI - [Mechanism of masticatory rhythm]. PMID- 11203317 TI - [Post-traumatic change of neuronal function]. PMID- 11203318 TI - Recommendations for the reporting of resected esophageal carcinomas. Association of Directors of Anatomic Surgical Pathology. PMID- 11203319 TI - Recommendations for the reporting of specimens containing oral cavity and oropharynx neoplasms. Association of Directors of Anatomic and Surgical Pathology. PMID- 11203320 TI - Recommendations for the reporting of surgical specimens containing uterine cervical neoplasms. Association of Directors of Anatomic and Surgical Pathology. PMID- 11203321 TI - Recommendations for the reporting of thyroid carcinomas. Association of Directors of Anatomic and Surgical Pathology. PMID- 11203322 TI - Nobel prizes: European Nobel Laureates in physiology and medicine (in fact in immunolgy). PMID- 11203323 TI - Murine models of Chlamydia trachomatis genital tract infection: use of mouse pneumonitis strain versus human strains. PMID- 11203324 TI - Outer surface protein A and arthritis in hamsters. PMID- 11203325 TI - Trasvenous permanent pacemaker implantation in neonates. PMID- 11203326 TI - Amiodarone-induced AV block and ventricular standstill. A forme fruste of an idiopathic long QT syndrome. PMID- 11203328 TI - Inferior vena cava obstruction secondary to permanent pacing. PMID- 11203327 TI - Digitoxin intoxication in a 79-year-old patient. A description of a case and review of the literature. PMID- 11203329 TI - Isolated cardiac echinococcosis in Cyprus. PMID- 11203330 TI - Breast cancer genetics. Implications of clinical practice. PMID- 11203331 TI - Breast cancer chemoprevention. PMID- 11203332 TI - Evidence-based clinical microbiology. PMID- 11203333 TI - Investigation of effects of acid citrate dextrose and EDTA on ability to quantitatively culture human immunodeficiency virus. PMID- 11203334 TI - Intrathecal use of colistin. PMID- 11203336 TI - 1999 Annual Meeting on Muscle and Cell Motility Physiology. Tokyo, Japan, 3-4 December 1999. Abstracts. PMID- 11203335 TI - Are alternative sources of parasitic (cysticercal) antigens necessary for diagnosis of neurocysticercosis? PMID- 11203337 TI - Women's health. PMID- 11203338 TI - Books: review symposium on women's health. Review essay. The past, present, and future of long-term care--a women's issue? PMID- 11203339 TI - Chemical restraint. PMID- 11203340 TI - Who is dying, doctor or patient? PMID- 11203342 TI - Marital status and suicide: some common methodological problems. PMID- 11203341 TI - Non-Hodgkin's lymphoma and nitrate in drinking water. PMID- 11203344 TI - Family doctor advice and pneumococcal vaccine uptake. PMID- 11203343 TI - Neonatal mortality by place of delivery in Sao Paulo, Brazil. PMID- 11203345 TI - ESRADI abstracts. PMID- 11203346 TI - IARC Working group on the evaluation of carcinogenic risks to humans: ionizing radiation, Part I, X- and gamma- radiation and neutrons. Lyon, France, 26 May-2 June 1999. PMID- 11203347 TI - A look back: the wonder drug. PMID- 11203348 TI - A look back: the sphygmomanometer. PMID- 11203349 TI - A look back: asthma. PMID- 11203350 TI - [Aging and work. Conclusive considerations]. PMID- 11203351 TI - [Prevention and therapy of diabetic retinopathy]. PMID- 11203352 TI - [Gottfried Ewald. Comments on cover picture]. PMID- 11203353 TI - Cervical hydrosonography in pregnancy to assess cervical length by transabdominal ultrasound. AB - BACKGROUND: Some women's cervices cannot be evaluated because they are obscured by obesity or vertex-presenting fetuses. Measuring cervical length in these cases is difficult or impossible. TECHNIQUE: We hypothesized that the problem of obscured cervices on transabdominal ultrasound could be resolved by introducing sterile water into the vagina, creating a hydroacoustic window between the vaginal lumen and the cervix. Women with unmeasurable cervices on transabdominal ultrasound had repeat studies after introduction of 60 mL of sterile water into their vaginas, and cervical length measurements taken were compared with those made on transvaginal scans. EXPERIENCE: Six pregnant women were studied (four singleton, one twin, and one triplet pregnancy). In all cases, previously unidentifiable cervices were seen adequately. No complications were noted. Statistical analysis (kappa 0.66) suggested good correlation between transabdominal cervical hydrosonography and transvaginal measurements of cervical length. CONCLUSION: Introducing water into the vagina at transabdominal ultrasound can make an obscured cervix visible and measurable. PMID- 11203355 TI - Proceedings of the Workshop on Tick-Borne Diseases of Livestock in the Mediterranean Area. Palermo, 3-6 March 1999. PMID- 11203354 TI - Frequency of cervical smear abnormalities within 3 years of normal cytology. PMID- 11203356 TI - Tics and Tourette's syndrome. PMID- 11203357 TI - The use of hypnosis in gastroscopy. PMID- 11203358 TI - [Increase in perforin-positive peripheral blood lymphocytes in extrinsic and intrinsic asthma]. AB - The cause of asthma which has been linked to a chronic, T-cell-mediated bronchial inflammation, remains unclear. A number of other T-lymphocyte-mediated, chronic inflammatory disorders have been associated with autoimmunity and there are data indicating that autoimmune phenomena might also be present in asthma. Expression of perforin, a cytotoxic molecule produced by lymphocytes, has been implicated in the pathogenesis of autoimmune disease. We therefore tested the hypothesis that allergic and intrinsic asthma might be associated with an increase in lymphocytes producing perforin by comparing the expression of intracellular perforin in peripheral blood lymphocytes of patients with extrinsic asthma (n = 13), intrinsic asthma (n = 7), and healthy (control subjects (n = 18). Lymphocytes were identified using flow cytometry and subdivided into CD3(+), CD4(+), CD8(+), CD16(+), and CD56(+) subpopulations after staining with appropriate monoclonal antibodies. The percentage of perforin-positive total lymphocytes as significantly elevated in patients with allergic as well as intrinsic asthma when compared with normal control subjects. Analysis of lymphocyte subpopulations also revealed a significant increase in the percentage of CD3(+), CD4(+), CD8(+), and CD56(+) cells expressing perforin in allergic asthma and a significant increase in the percentage of CD4(+), and CD56(+) cells in intrinsic asthma when compare with healthy control subjects. Perforin expression in CD4(+) cells in intrinsic asthma was also significantly elevated compared with allergic asthma. We conclude that allergic and intrinsic asthma is associated with increased expression of perforin in T-lymphocyte subsets. PMID- 11203359 TI - [Extent of our knowledge on schizophrenia]. PMID- 11203360 TI - Severe hypothyroidism after chemotherapy and locoregional irradiation for breast cancer. PMID- 11203361 TI - [Tiazides and betablockers in the treatment of hypertension]. PMID- 11203362 TI - [Revascularization in chronic renal failure]. PMID- 11203363 TI - [Anticoagulant treatment in nonrheumatic atrial fibrillation]. PMID- 11203364 TI - International symposium: Fractals 2000 in biology and medicine. Ascona, Switzerland, 7-11 March 2000. Abstracts. PMID- 11203365 TI - [The image of the dentist and the dead season]. PMID- 11203366 TI - [Infectious diseases in the dental office]. PMID- 11203367 TI - ["Draw me a dentist!"]. PMID- 11203368 TI - [The information platform of the SSO (Societe Suisse d'Odonto-Stomatologie]. PMID- 11203369 TI - [The current trends in implantology. A report on the annual meeting of the Societe Suisse d'Implantologie Orale (SSIO) of 6 September 2000 at Bern]. PMID- 11203370 TI - [The social and political aspects in geriatric dentistry. A report on the SSO Congress at Interlaken, 7, 8 and 9 September 2000 (1). Societe Suisse d'Odonto Stomatologie]. PMID- 11203371 TI - Artificial life. Boids of a feather flock together. PMID- 11203372 TI - Biomathematics--patterns. Spiral slime. PMID- 11203373 TI - Cervical disc herniation presenting with acute myelopathy. PMID- 11203374 TI - Evaded bioethics. PMID- 11203375 TI - Use of nitric oxide inhalation in COPD. PMID- 11203376 TI - Discovery of PAI-1 in plasma. PMID- 11203377 TI - Amount of paraformaldehyde for sample fixation markedly affects the quality of platelet assessment by flow cytometry: experience from two clinical trials. PMID- 11203378 TI - Masking is addictive triggering not noise. PMID- 11203380 TI - Bibliography of toxinology. PMID- 11203379 TI - 6th Panamerican Congress on Animal, Plant and Microbial Toxins of the International Society on Toxinology, Panamerican Section. An international meeting on toxins as problems, tools and solutions. 21-26 September 1998. Margarita Island, Venezuela. Abstracts. PMID- 11203381 TI - Mitochondria and chloroplasts: localized and delocalized bioenergetic transduction. PMID- 11203382 TI - Copper chaperones in bacteria: association with copper-transporting ATPases. PMID- 11203383 TI - The REPRO server: finding protein internal sequence repeats through the Web. PMID- 11203384 TI - IKKalpha-/- mice share phenotype with pupoid fetus (pf/pf) and repeated epilation (Er/Er) mutant mice. PMID- 11203385 TI - Hsp70 (DnaK)--an evolution facilitator? PMID- 11203386 TI - Exploring histones and their relatives with the Histone Sequence Database. PMID- 11203387 TI - RUMMAGE--a high-throughput sequence annotation system. PMID- 11203388 TI - Stochastic multidimensional hypercubes and inverse agonism. PMID- 11203389 TI - Forgotten target for marijuana: the endocannabinoid system in the gut. PMID- 11203390 TI - Astrocyte-neurone crosstalk: variants of the same language? PMID- 11203391 TI - Considerations about Professor Eckert's lecture on the occasion of WAA VP/Pfizer Award. PMID- 11203392 TI - [Dissertations defended in 2000]. PMID- 11203393 TI - [A gathering of the chief pulmonary tuberculosis specialists in the branches of the Armed Forces, military districts and the Navy]. PMID- 11203394 TI - [A clinical expert conference of specialists of Moscow region military medical commissions]. PMID- 11203395 TI - [Dissertations defended in 2000]. PMID- 11203396 TI - [Modern diagnostic and therapeutic technologies for infectious patients]. PMID- 11203397 TI - Perioperative Transfusion Triggers for Red Blood Cells. AB - Perioperative transfusion triggers for red blood cell (RBC) transfusion include physiologic signs of inadequate oxygenation of the entire organism or a specific organ, hemoglobin (Hb) concentration and logistic aspects such as experience of anesthesiologists and surgeons, predictability and magnitude of blood loss and time required for a Hb determination and RBC delivery. At a Hb concentration <6 g/dL a RBC transfusion may be given, however, if the patient is hemodynamically stable one may opt not to transfuse. With Hb concentrations between 6 g/dL and 10 g/dL physiologic signs of inadequate oxygenation decide on RBC transfusion. In absence of hypovolemia signs of inadequate oxygenation include tachycardia and hypotension, an O2 extraction>50%, a a mixed-venous O2 partial pressure <4.3 kPa (32 mmHg), a decrease of O2 consumption >10% (not otherwise explained) and signs of locally deficient oxygenation such as myocardial ischemia. At Hb concentrations >10 g/dL, RBC transfusions are rarely, if ever, indicated. PMID- 11203398 TI - [The article by Dr. Mey et al., Therapy-refractory thrombocytopenia in chronic hepatitis C. Casuistics]. PMID- 11203399 TI - [Park bench paralysis and bottle sign symptoms]. PMID- 11203400 TI - [On the 125th anniversary of the birth of A. A. Ukhtomskii]. PMID- 11203401 TI - "Immunization of newborns in the tropics." The Gambia, 25-27 November 1999. PMID- 11203402 TI - The estimation of mortality due to rotavirus infections in sub-Saharan Africa. PMID- 11203403 TI - Vaccine-induced antibodies by commercial test kits, the case of the Rubini mumps and the Edmonston-Zagreb measles vaccine strains. PMID- 11203404 TI - [On the 80th birthday of Evgenii Nikolaevich Sokolov]. PMID- 11203405 TI - [Normal and impaired fracture healing]. PMID- 11203406 TI - [Consensus meeting. Acute pancreatitis]. PMID- 11203407 TI - Proceedings of the Nordic Oto-Laryngological Society's XXVIIth Congress. 12-15 August 1999. Odense, Denmark. PMID- 11203408 TI - Experimental and clinical-therapeutic features of asthma. Proceedings from the international meeting in Naples, Italy. June 7-8, 1999. PMID- 11203409 TI - A case for co-ordinated investigation and reporting of hypersensitivity-type drug reactions in the UK. PMID- 11203410 TI - [Consensus conference: Indications for curarization in anesthesia. Saint-Mande, 8 July 1999. Proceedings]. PMID- 11203411 TI - [Inhaled corticosteroids and wheezing post-bronchiolitis]. AB - OBJECTIVE: To determine whether inhaled corticosteroid therapy given for 3 months after mild bronchiolitis decreases the incidence and/or severity of wheezing in the following 12 months. DESIGN: Multicentric, single-blind, controlled, randomised intervention study. SETTING: Primary Health Care Centers in Lezo, Beraun, Andoain and Irun (Gipuzkoa, Spain). PATIENTS: Infants less than 12 months old (n = 94) diagnosed with mild bronchiolitis. INTERVENTION: We established two groups of patients: group 1 (n = 47) was treated with inhaled beclomethasone (250 pg/12 hours) using a valved holding chamber (Babyhaler); the treatment started eight days after diagnosis of bronchiolitis and lasted 3 months. Group 2 (n = 47) received no treatment. We compared the number of wheezing episodes and their severity during the intervention period (3 months) and the follow-up period (12 months) with the Students t-test and the Chi-squared test. RESULTS: We studied 89 infants (group 1, n = 42; group 2, n = 47), 67% of whom wheezed during the study period (15 months). There were no significant differences between the treatment and the control group in the study periods. CONCLUSIONS: Inhaled beclomethasone given for 3 months does not significantly modify the occurrence of wheezing episodes during the treatment period or during the following 12 months. PMID- 11203412 TI - [Outpatient management of children with viral meningitis]. AB - OBJECTIVE: To describe our experience in the extrahospitalary management of children with suspected viral meningitis (YM). METHOD: Between April and July 1997. 156 children were diagnosed of YM in our hospital and 150 managed as outpatients, after being a few hours in our emergency department. All of them were suspected to have VM attending usual clinical and laboratory findings and were discharged with cautious instructions to demand a new assessment. We contacted telephonically with them one month and six months later. RESULTS: All the children with suspected viral meningitis and managed as outpatients had negative blood and CSF cultures and all of them did well. Telephonically, 104 children (69.3%) referred transient headache or back pain. and 20 of these (13.3% of all the 150) came again to our hospital, and 4 required rest for a few hours (4-12 hours) in our observation setting. Children with suspected VM didn't go to school during 5.9 x 6.1 days (1-30 days) and 71 (47.3%) were absent less than 3 days. CONCLUSION: Outpatient management of most of the children with suspected VM is possible. When a patient is sent home, detailed instructions must be given to the family. PMID- 11203413 TI - [Klinefelter 48 XXYY syndrome. Case report]. PMID- 11203414 TI - [Hypermenorrhea in teenagers as a cause of iron-deficiency anemia and hospital admission]. PMID- 11203415 TI - [Evaluation of a transcutaneous bilirubinometer]. AB - OBJECTIVE: Transcutaneous bilirubinometers are useful in screening and monitoring neonatal hyperbilirubinemia. These instruments reduce the number of blood samples needed, but their validity has been questioned. The aim of this study was to evaluate the accuracy and reliability of a classic transcutaneous bilirubinometer. METHOD: Descriptive observational cross-sectional study of a sam ple of 117 simultaneous measurements of transcutaneous and serum bilirubin in 82 jaundiced newborn infants. We analyzed the agreement between repeat measurements and measurements in different sites. We developed predictive models of serum bilirubin and analyzed their validity. RESULTS: All points of measurement displayed excellent agreement between repeat measures (intraclass correlation co efficient higher than 0.92). Forehead measurements had a linear correlation coefficient of 0.75; in the sternum II-near correlation coefficient varied according to the absence or presence of phototherapy (0.86 and 0.54 respectively). The error intervals in which predictions of se-rum bilirubin were found were #+ 2 mg/dl for low values and #+ 4 mg/dl for high values (#> 15 mg/dl). CONCLUSIONS: Reliability of the transcutaneous bilirubinometer evaluated was high, but the substantial degree of error in se-rum bilirubin make its accuracy questionable, especially in patients with high levels. PMID- 11203416 TI - [Continuing increase in the incidence of serogroup C meningococcal disease. Should we decide to vaccinate?]. PMID- 11203417 TI - [Hypernatremia as postsurgical complication of hepatic hydatid cyst]. PMID- 11203418 TI - [Sterilization in the dermatology outpatient clinic]. PMID- 11203419 TI - [Aesthetics and mortal risk]. PMID- 11203420 TI - Potencies of newer fluoroquinolones against Viridans group Streptococciisolated in 637 cases of bloodstream infection in the SENTRY Antimicrobial Surveillance Program (1997 to 1999): beyond Canada! PMID- 11203421 TI - Use of small amounts of ultrasound guided air for injections. PMID- 11203422 TI - Steroid psychosis after an intra-articular injection. PMID- 11203423 TI - Familial macrophagic myofasciitis. PMID- 11203424 TI - [Minimally invasive cardiac surgery]. PMID- 11203425 TI - Cellular resistance to homocysteine: a key for longevity. PMID- 11203426 TI - Identification of HIV-1 in the aortic wall of AIDS patients. PMID- 11203427 TI - Atherosclerosis, type 1 collagen cross-linking and homocysteine. PMID- 11203428 TI - Acute normovolemic hemodilution. PMID- 11203429 TI - A possible cause of cardiovascular collapse during anesthesia: long-term use of St. John's Wort. PMID- 11203430 TI - HIV-1: molecular biology and pathogenesis. PMID- 11203431 TI - Proceedings of the South-Eastern Organ Procurement Foundation meeting. 16 September 1999, Memphis, Tennessee, USA. PMID- 11203432 TI - Lessons learned from a full-scale bioterrorism exercise. PMID- 11203433 TI - Cyclooxygenases in the central nervous system: implications for treatment of neurological disorders. AB - Recognition of two isoforms of cyclooxygenase and reports that nonsteroidal anti inflammatory drugs may be beneficial in devastating neurological conditions such as Alzheimer's disease have led to increased interest in cyclooxygenase function in the nervous system. In the present paper we review current data on the multiplicity of cyclooxygenase and prostaglandin mediated effects in the central nervous system (CNS). We discuss CNS cells types, including neurons, glia, and cerebrovascular elements, where cyclooxygenases-1 and -2 are expressed under normal conditions or can be induced by physiological or pathological stimuli. We also address physiological processes such as pain sensitization, CNS inflammation and fever induction that are regulated or modified by cyclooxygenase activity. Finally, we describe potential roles of cyclooxygenase in neurological diseases and rationales for nonsteroidal anti-inflammatory drug use in the treatment of neurodegenerative disorders, stroke and CNS injury. PMID- 11203434 TI - Protection against ozone-induced pulmonary inflammation and cell death by endotoxin pretreatment in mice: role of HO-1. AB - Ozone is a ubiquitous air pollutant that can cause acute pulmonary inflammation and cell injury and may contribute to the exacerbation of chronic pulmonary diseases. The molecular mechanisms of ozone-induced cell injury, as well as protective mechanisms against ozone-injury, are not well understood. Since ozone is a reactive oxidant, and heme oxygenase-1 (HO-1) is an antioxidant enzyme induced by many oxidative stimuli, we hypothesized that HO-1 is one of the protective mechanisms against ozone-induced cell injury, as well as pulmonary inflammation. In the current study, C57Bl/6 mice were pretreated with a low level of endotoxin (lipopolysaccharide, LPS) (0.5 mg/kg) to induce HO-1, and 16 h later were exposed to 1 ppm ozone for 3 h. Endotoxin pretreatment caused a significant protection against ozone-induced pulmonary inflammation and cell injury in bronchoalveolar lavage (BAL) cells. The protection by endotoxin pretreatment against ozone-induced inflammation and necrosis in BAL cells was abolished by the cotreatment with a heme oxygenase inhibitor, tin protoporphyrin IX dichloride (SnPP), suggesting that HO-1 is responsible for the protection against ozone induced pulmonary inflammation and BAL cell necrosis. Therefore, since HO-1 is induced following ozone exposure, HO-1 may contribute to the development of cellular adaptation to chronic ozone exposure. PMID- 11203435 TI - Fetal cardiotocography during cesarean section. PMID- 11203436 TI - Endoscopic ultrasound. PMID- 11203437 TI - Endoscopic valvuloplasty for gastroesophageal reflux disease. PMID- 11203438 TI - A comparison of virtual and conventional colonoscopy for the detection of colorectal polyps. PMID- 11203439 TI - Safe, low-distortion tape touch method for fungal slide mounts. PMID- 11203440 TI - Evaluation of the toxicity of Solanum lycocarpum in the reproductive system of male mice and rats. AB - Powdered Solanum lycocarpum fruit is commonly used to treat diabetes, but apparently no studies have been conducted to evaluate potential adverse side effects. In the present paper the toxic effect of S. lycocarpum was evaluated in adult male Wistar rats and Swiss mice. The administration of an aqueous extract prepared using a powder obtained from the S. lycocarpum fruit at two different dose levels (60 mg/15 ml and 120 mg/15 ml distilled water for rats and 30 mg/15 ml and 60 mg/15 ml distilled water for mice, twice daily for 5 days in each case) did not produce body weight variations in either species although a significant weight change was observed in some organs. Significant weight loss was observed only in the ventral prostate of mice receiving the high dose treatment. These results suggest a toxic effect of S. lycocarpum on the male reproductive system of the Swiss mouse, with possible antiandrogenic activity, but there was no apparent antifertility activity in rats at the doses given. PMID- 11203441 TI - [The use of acetylsalicylic acid in patients with ischemic cardiomyopathy cared for in Spanish emergency services (results of the EVICURE Study). Evaluacion del Manejo de la cardiopatia isquemica en los Servicios de Urgencias Hospitalarios of the Sociedad Espanola de Medicina de Urgencias y Emergencias (SEMES)]. AB - BACKGROUND: Acetyl salicylic acid is a drug with demonstrated effectiveness in ischemic cardiomyopathy. The objective of our study was to know the use of this drug in the emergency services of Spain. PATIENTS AND METHOD: The EVICURE study analyzes the use of acetyl salicylic acid in 35 emergency services of Spanish hospitals. RESULTS: 2,168 patients were studied. Of the 473 patients with stable angina, 9.2% received acetyl salicylic acid before going to the hospital and 90,7% at the arrival to the hospital, of 1,067 with unstable angina 13% received acetyl salicylic acid before the arrival to the hospital and 56% at the arrival to the hospital. Of 600 patients affected of myocardial infarction only 17% received acetyl salicylic acid before the arrival to the hospital and 59.8% received this drug in the emergency room. CONCLUSIONS: The use of acetyl salicylic acid in patients affected of ischemic cardiopathy assisted in the emergency services of Spain is improperly low. PMID- 11203443 TI - Hydrocephalus. PMID- 11203442 TI - Structural Barriers and Facilitators in HIV Prevention. Meeting proceedings. February 22-23, 1999. PMID- 11203444 TI - [Proceedings of the Berner Symposium on Pancreatic Surgery. November 1999]. PMID- 11203445 TI - Dirk Durrer (1918-1984). PMID- 11203446 TI - Too many good people: not enough awards. PMID- 11203447 TI - 4Oth Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). PMID- 11203448 TI - 40th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). PMID- 11203449 TI - American Association for Cancer Research: dendritic cells: strategies and vaccines. April 1-5, 2000, San Francisco, CA, USA. AB - Several major sessions on dendritic cells (DCs) reflected the importance of these members of the immune system within cancer research. Technical hurdles to their routine propagation were largely overcome within the past decade, so the study of precursors, as well as the numerous types of dendritic cells, is the focus of intense research. In vitro studies were presented that described further refinements in dendritic cells are collected and culture. Cytokines and other growth factors have been analysed to assess their contribution to the ability of dendritic cells to intake, process and present antigen. In some instances, the dendritic cells themselves are genetically altered to improve their natural biological activity. Many studies have advanced from in vitro work and demonstrated utility in various animal models. Ultimately, there is the hopeful, steady progress into the increasing numbers of experimental immunotherapies against human cancer. PMID- 11203450 TI - American Association for Cancer Research: Clinical trials of immunotherapeutics and immunologic monitoring. April 1-5, 2000, San Francisco, CA, USA. AB - A major session at this annual gathering of the cancer researchers from around the globe dealt with the current state of immunotherapy for cancer. Immunotherapy is a form of cancer treatment that enhances its scientific promise and legitimacy with each passing year. As a result, this topic has become one of the most highly attended and anticipated of all the sessions during the AACR. This year's session included further progress from the laboratory to the clinic involving an ever increasing number of cancers. For example, brain, lung and prostate cancer are now as well-represented as melanoma and lymphoma at such forums. This year's session continued the trend of impressive biosafety of both cell- and antibody based vaccines. Therefore, these cancer vaccines offer optimism in treatment benefit as well as a minimal impact on quality of life. Lastly, the increasing number of clinical responses allows for true immunological monitoring, as scientists strive to unlock the mysteries behind what makes one patient respond to treatment and another progress. Several groups discussed in vitro immune parameters that were studied in concert with their clinical trials. Others discussed ways in which those in the immunotherapy community can work towards more reliable immune monitoring and ultimately a surrogate marker for response. PMID- 11203451 TI - American Association for Cancer Research: potential target antigens for cancer immunotherapy. April 1-5, 2000, San Francisco, CA, USA. AB - The 91st annual meeting of the American Association for Cancer Research (AACR) convened this year in San Francisco, USA. Nearly 5600 abstracts were published within ten broad research categories ranging from basic molecular, cellular and pharmaceutical research to cancer epidemiology and prevention. The largest number of poster presentations belonged in the 'Pharmacological and Experimental Therapeutics' section, followed closely by 'Molecular Biology' and 'Cell and Tumour Biology'. Novel tumour antigens and their potential application in cancer immunotherapy were displayed primarily in a section categorised as 'Immunology/Preclinical and Clinical'. This article reports some of the significant tumour antigen-related studies presented at this meeting. PMID- 11203452 TI - The future of plasma derivatives. 17-18 April, 2000, Brussels, Belgium. AB - This two-day meeting was organised by Life Sciences Division of IBC Global Conferences Limited. It was attended by an international, multidisciplinary group of experts with differing expertise and perspectives on the provision of therapeutic products derived from human plasma. The delegates ranged from those involved with the collection of plasma donations, the scientists dedicated to improving the screening tests for virus markers, quality assurance personnel, clinicians, marketing and business managers, members of regulatory agencies in Europe and the Food and Drug Administration (FDA), providers of services to the industry and last, but not least, patient groups were represented. Fifteen to twenty countries were represented by the delegates and speakers. Although it might seem that the background and expertise of the audience was so wide that the lectures would have to be superficial, this was not the case. The whole process from plasma (or blood) collection to injection of a product into a patient was already well-known to senior members of the various organisations present and there is a tremendous amount of inter-dependence which enhances the necessary level of understanding. Nevertheless, the speakers were able to expand the knowledge of the delegates by their lucid and detailed presentations. The issues associated with development and implementation of new technologies, such as new NAT tests and different virus inactivation processes, were fully described. The spotlight also fell on the effects that changing patterns of demand for individual therapeutic proteins are having and will continue to have on the economics of the industry and on patient groups. Unlike other manufactured products, the raw material is the same for all plasma-derived products. Demand for all these products is limited by the availability of the donated plasma. Ideal demand for economic reasons is a balance of the extractable proteins in the donation. The implementation of European regulations was reviewed from the industry and from the regulators. Flexibility shown by the FDA in responding to the shortages of iv. immunoglobulins (Ig) was described, particularly with regard to clinical evaluation. Finally, the rationale for the need to revise the CPMP guidelines for clinical evaluation of certain plasma products was described as were the difficulties to be expected with implementation. PMID- 11203453 TI - SMI's 2nd Annual Superbugs and Superdrugs Conference: innovations in anti infectives. AB - The emergence of the 'Superbugs', resistant bacterial pathogens, is being aggressively met by the anti-infective community, both academia and industry, with an assortment of classical and novel approaches to control these resistant pathogens. The launch of improved quinolones (gatifloxacin and moxifloxacin), the launch of a new class of protein synthesis inhibitors (oxazolidinones; linezolid) and the ushering-in of the applied genomics age, all offer hope for the future control of resistant bacteria. The seemingly imminent development and completion of the first lipopeptide, daptomycin, offers great hope for the control of Gram positive resistant pathogens. The first cationic peptide, IB-367, designed to combat the niche medical need of mucositis and the development of a specific antistaphylococcal glycopeptide. BI-397, all will precede the first wave of genomic-targets-based drug candidates, as the antimicrobial genomics effort remains in the target identification and validation stages of early discovery. PMID- 11203454 TI - 9th International Conference on Obesity, NIDDM, adipogenesis and insulin resistance. AB - The 9th International Conference on Obesity, NIDDM, Adipogenesis and Insulin Resistance was held between 3rd and 5th April, 2000 in London, UK. The three day conference was attended by more than 100 delegates from both academic and industrial institutions. Conference topics covered the use of genetics in obesity and diabetes, etiology and implications of treatment for obesity, progress in identification of new obesity and Type 2 diabetes drug targets, islet cell targets, progress in drugs for insulin enhancement and sensitisation, adipogenesis and insulin resistance. Below are meeting highlights closely related to new drug developments and drug target identification in these therapeutic areas. PMID- 11203455 TI - The DOP system: a manifestation of social exclusion. A personal commentary on 'Alcohol consumption amongst South African farm workers: a post-apartheid challenge, by L. London 1999'. PMID- 11203456 TI - Quiz case. Atypical gout arthritis. PMID- 11203457 TI - Consensus guidelines on management of childhood asthma in India. PMID- 11203458 TI - Consensus guidelines on management of childhood asthma in India: role of ipatropium bromide in acute episode. PMID- 11203459 TI - Role of Ketotifen in asthma. PMID- 11203461 TI - Monoamine oxidase inhibitors in rheumatoid arthritis-anti-tumor necrosis factor? PMID- 11203460 TI - Deferiprone for thalassemia major. PMID- 11203462 TI - Report of the second annual walker's cay colloqium on cancer vaccines and immunotherapy, March 8-11, 2000. PMID- 11203463 TI - The nuclear export signal within the adenovirus E4orf6 protein contributes to several steps in the viral life cycle. PMID- 11203464 TI - The antinociceptive effect of antidepressants--noradrenergic versus serotonergic modes of action? PMID- 11203465 TI - A hydrodynamic model for hindered diffusion of proteins and micelles in hydrogels. PMID- 11203466 TI - The model of Snyder et al. does not simulate graded Ca(2+) release from the cardiac sarcoplasmic reticulum in intact cells. PMID- 11203467 TI - Measuring both femora? PMID- 11203468 TI - [Natural medicine and its representatives]. PMID- 11203469 TI - A provider's perspective: current issues in providing and funding complementary medical care. PMID- 11203470 TI - [Montgomery GH, DuHamel KN, Redd WH: A meta-analysis of hypnotically induced analgesia: How effective is hypnosis? Int J Clin Exp Hypn 2000; 48: 138-153]. PMID- 11203471 TI - [Effectiveness of acupuncture in chronic pain--systematic overview. Ezzo J, Berman B, Hadhazy VA, Jadad AR, Lao L, Singh BB: Is acupuncture effective for the treatment of chronic pain: A systematic review. Pain 2000; 86:217-225]. PMID- 11203472 TI - [Hui KK, Liu J, Makris N, Gollub RL, CHen AJ, Moore CI, Kennedy DN, Rosen BR, Kwong KK: Acupuncture modulates the limbic system and subcortical gray structures of the human brain: Evidence from fMRI studies in normal subjects. Hum Brain Mapp 2000; 9: 13-25]. PMID- 11203473 TI - [Meeting report: 1. Union congress, May 26-27 2000, Berne. Complementary medicine and school medicine: combined for the patient]. PMID- 11203474 TI - [Swiss Medical Society for Phytotherapy. Mahonia aquifolium (Pursh) Nutt. as a dermatologic plant: pharmacologic and clinico-pharmacologic studies]. PMID- 11203476 TI - CNS drugs III: psychotherapeutics. AB - This two-day symposium reviewed specific aspects of current drug development for psychiatric disorders. The aim was to identify how existing drugs could he improved and what approaches could he adopted to develop new drugs acting by different mechanisms. The meeting was attended by approximately 50 delegates, mainly from multinational pharmaceutical companies or smaller private biotechnology based companies with a few academic clinicians and preclinical scientists. The topics covered on the first day included the influence of genomics and proteomics on drug discovery with reference to antipsychotics, GABAA receptor subunit specific compounds as a route to improved anxiolytics. AMPA receptor modulators as add-on therapy in schizophrenia and corticotrophin releasing factor receptors as targets in depression. The second day placed a greater emphasis on drugs influencing amine neurotransmission; an aspect already raised on the first day by discussion of 5-HT-moduline. The main areas covered were how serotonergic ligands could he used with greater effect in depression and schizophrenia, the therapeutic value of serotonin noradrenaline uptake inhibitors (SNRIs) and the potential clinical value of new amine re-uptake inhibitors. Finally, the meeting discussed the impact of various technological advances in genetics. neuroimaging and psychometric testing in psychotherapeutic drug discovery. PMID- 11203475 TI - 100th American society for microbiology annual meeting. AB - The 100th ASM Annual Meeting, attended by approximately 10,000 delegates, continued the trend of concentrating on bacteria and antibacterial therapy, mixed with genomics and a diverse number of additional topics. Of the various marketable drug classes, the quinolones received attention with respect to susceptibility studies and several drug comparison studies. New marketable drugs were also of interest, especially given the reservoirs of resistance presented by several speakers. Drugs in development include the antibacterial daptomycin and protegrins and the antifungal lipodepsinonapeptides and echinocandins, to name a few. It is still unclear whether or not antibiotic treatment regimens for Chlamydia pneumonia will he necessary, as association of this bacteria with several chronic diseases, such as atherosclerosis and asthma, was discussed. The development of novel antibiotics was highlighted and the potential role that microbial genomics technology could play was a recurring theme. In fact, a number of symposia treated the increasingly popular topic of genomics in a variety of themes, including phenotyping arrays, transcriptional profiling, proteomics, expression profiling, genome sequencing, target areas or essentiality of genes via gene knockout systems, the role of genomics in pharmaceutical development and fungal genomics. Similarly, genomics plays a role in developing a deeper appreciation for classical areas of interest in microbial physiology, such as gene regulation, cell division, fatty acid biosynthesis, DNA replication and cell signalling. Even in the bio-inorganic field of study in microbial metabolite activation, genomics plays a role. The sequencing of the large gene clusters of the auxiliary proteins necessary to synthesise or activate the metallo-proteins provided insights into the mechanisms of activation of these microbial enzymes, including the genes for the nif gene cluster in Azotobacter vinelandii, the urease from Kiebsiella aerogenes and the three hydrogenases in Ralstonia eutropha. PMID- 11203477 TI - Proceedings of a workshop on self-reported outcome measures in audiological rehabilitation including hearing aids. Eriksholm, Denmark, September 1-3, 1999. PMID- 11203478 TI - Quality and outcomes assessment in gastrointestinal endoscopy. American Society for Gastrointestinal Endoscopy. PMID- 11203479 TI - Appropriate use of gastrointestinal endoscopy. American Society for Gastrointestinal Endoscopy. PMID- 11203480 TI - Modifications in endoscopic practice for pediatric patients. PMID- 11203481 TI - Endoscopic therapy of chronic pancreatitis. American Society for Gastrointestinal Endoscopy. PMID- 11203482 TI - Modifications in endoscopic practice for the elderly. American Society for Gastrointestinal Endoscopy. PMID- 11203483 TI - Role of endoscopic ultrasonography. American Society for Gastrointestinal Endoscopy. PMID- 11203484 TI - Technology status report evaluation. Endoscopic mucosal resection. PMID- 11203485 TI - Technology status evaluation report. High resolution and high-magnification endoscopy. PMID- 11203486 TI - Is Endometriosis Potentially Malignant? Proceedings of the 3rd Japan Conference on Endometriosis. Kanagawa, Japan, April 22, 2000. PMID- 11203487 TI - [Fluorescence properties and metabolic features of fluorescein]. PMID- 11203488 TI - Modern prostate brachytherapy: prostate specific antigen results in 219 patients with up to 12 years of observed follow-up. PMID- 11203489 TI - Accuracy of diagnosis by guided biopsy of renal mass lesions classified indeterminate by imaging studies. PMID- 11203490 TI - Antenatal minimal hydronephrosis: is its follow-up an unnecessary cause of concern? PMID- 11203491 TI - Early orchiopexy: prepubertal intratubular germ cell neoplasia and fertility outcome. PMID- 11203492 TI - Resuscitation 2000. Antwerp, Belgium. Abstracts. PMID- 11203493 TI - Arteriovenous malformations time line: radiation therapy. PMID- 11203494 TI - Surgery for sphenoid sinus abscess. PMID- 11203495 TI - Society merger? PMID- 11203496 TI - Bibliography of Toxinology. PMID- 11203497 TI - Use of meta-analysis to draw conclusions as to relative efficacy is illegitimate and should not be accepted. PMID- 11203498 TI - Tetanus-diphtheria booster in non-responding tetanus-diphtheria vaccinees. PMID- 11203499 TI - Influenza season 2000/01 vaccine dose-response studies. PMID- 11203500 TI - Hepatitis A: how to match prevention strategies to changing epidemiology. PMID- 11203501 TI - More HIV resistance testing needed, according to survey. PMID- 11203502 TI - Broca and the beginning of modern neurosurgery. AB - The study presents Broca's pioneering efforts on cerebral localizations and craniotopography and their application on the first craniotomy based on cerebral localization. PMID- 11203504 TI - Central nervous system paracoccidioidomycosis: case report. PMID- 11203503 TI - Non familial episodic ataxia possibly associated with the use of nicotine: case report. PMID- 11203505 TI - Continuing Care in Adult Cardiology: Living with a Cardiac Diagnosis. Preface. PMID- 11203506 TI - Acute Care Cardiology, Preface. PMID- 11203507 TI - [One step ahead and/or two steps back?]. PMID- 11203508 TI - Conducting geriatric dental research with cognitively impaired adults. AB - A growth in research focusing on the oral health of older adults has been evident in recent years. However, there are new and complex challenges for geriatric dental researchers studying the increasingly functionally dependent and cognitively impaired older adult population. Many geriatric dental studies have under-reported oral disease prevalence and incidence by excluding adults who are cognitively impaired and/or behaviourally difficult. To ensure representative samples of older adult populations are studied, traditional oral epidemiological protocols in studies with cognitively impaired adults, require additional components detailing: (1) communication and behaviour management strategies for cognitively impaired adults; and (2) methodologies to facilitate the completion of dental examinations. A description of such additional protocol components is presented, along with a discussion of the use of cognitive testing tools by dental researchers. PMID- 11203510 TI - Geriatric dentistry in the next millennium: opportunities for leadership in oral health. AB - "The twentieth century will be remembered chiefly, not as an age of political conflicts and technical inventions, but as an age in which human society dared to think of the health of the whole human race as a practical objective." Arnold Toynbee, British historian. Individuals throughout the world often view the passage of a new year as a time for re-evaluation of personal and/or professionals goals. The new millennium offers the dental profession a chance to view the future and observe the challenges and opportunities facing it. Professor Toynbee's observation is particularly poignant when one considers the improvements in oral health made in the last 100 years. Caries, once considered a ubiquitous oral disease, has been prevented in some children in developed countries. Research on periodontal disease continues to identify risk factors and the pathobiological mechanisms underlying the disease. Concurrently the population of the world is aging presenting new opportunities for improving oral health. In this paper the data on aging, chronic diseases and oral health is largely from the US but reflects to varying degrees other industrial countries. By integrating these demographic, epidemiologic and biologic data, one can paint a portrait of the future dental patient and their oral health needs. From this portrait, dental professionals can identify leadership opportunities to improve the oral health of an aging world population. PMID- 11203509 TI - Food choice by older people: the use of semi-structured interviews with open and closed questions. AB - OBJECTIVE: To evaluate difficulty chewing, consequent food choice and impacts using both open and closed questions within a semi-structured interview format. DESIGN: A cross-sectional study using a semi-structured interview (SSI) with open and closed questions. SETTING: Independently living people in South-West London interviewed in their own homes. SUBJECTS: A group of 54, edentate people (mean age 82, R = 60-93 years) were studied. RESULTS: Most subjects (69%) expressed difficulty eating at least one type of food, half were unwilling to eat the foods they found difficult, others were conscious of cooking longer or cutting smaller in order to manage these foods, although no one accepted that they overcooked food. There were dramatic differences in the number of subjects expressing difficulty to chew various foods when responding to open and closed questions. Roast beef proved a good discriminator in this group of predominantly English subjects. The importance of the questioning process was also shown by the discrepancy of responses between variously prepared apples and the inability of any subjects to bite an unpeeled apple. CONCLUSIONS: For sensitive appraisal of food choice it is obviously essential to assess relevant foods, for the culture of the group being studied. Open questions provide a way of exploring which are the appropriate foods and food preparation as criteria to assess perceived chewing ability and treatment benefit. The semi-structured interview method is particularly valuable for the study of older people. Closed questions provide different information which is also necessary to secure recall by older people. PMID- 11203511 TI - Oral health care among nursing home residents in Avon. AB - OBJECTIVE: To assess personal oral health care standards among frail, elderly and infirm nursing home residents prior to developing and evaluating a health promotion intervention. DESIGN: Descriptive survey, interview and clinical data. SETTING: 22 randomly selected nursing homes in the Bristol area. METHOD: 412 residents with denture(s) and/or natural teeth, and giving informed consent to the study were interviewed about dental attendance and current dental problems. A clinical examination assessed levels of oral and denture hygiene, denture-related stomatitis, gingivitis, calculus and root caries. RESULTS: Less than half the subjects (mean age 84.5 years) were ambulant. Over 70% had not seen a dentist for over 5 years, and 22% reported a current dental problem. Among denture wearers, 82% were unable to clean their dentures; staff cleaned dentures for 64%. Denture related stomatitis affected 33%, and unhygienic dentures were worn by 95% of subjects. Among dentate subjects (mean number of teeth 11.6), 75% were unable to clean their teeth yet none received regular assistance. On average, two-thirds of each tooth surface were covered in plaque. Gingivitis was moderately severe. Calculus was present in 82% of subjects and root caries in 63% of subjects. CONCLUSIONS: Most residents required help with oral health care but many did not receive it. Residents' levels of plaque and associated dental disease were high. Staff did not effectively perform oral health care appropriate to residents' needs. Further research to evaluate an oral health care training programme for care staff is planned. PMID- 11203512 TI - Amalgam fillings and cognitive abilities in a representative sample of the elderly population. AB - OBJECTIVES: The ongoing controversial discussion about a possible negative effect of amalgam fillings on the cognitive abilities and the pathogenesis dementia was the objective of the present study. SAMPLE: A total of 300 patients aged from 70 to 103 years were selected from the multidisciplinary 'Berlin Aging Study' (BASE). The sample was heterogeneous concerning lifestyle, education and social prestige. According to their dental state subjects were allocated into three groups: edentate > or = 20 years (I) and residual teeth without (II) or with (III) amalgam restorations. All groups were matched for age and gender. DESIGN: Dental examinations and various psychiatric as well as psychological assessments were carried out by professionals within the protocol of the BASE. Tests were chosen to reveal the presence and degree of dementia and assess cognitive abilities such as 'perceptual speed', 'reasoning', 'memory', 'fluency' and 'knowledge'. RESULTS: The present findings negate a correlation between the dental state and the pathogenesis of dementia and the physiological age-related decline in cognitive abilities. Thus the presence of amalgam fillings did neither correlate to a demented mental condition nor an impaired cognitive performance. PMID- 11203513 TI - Success of dental implants in elderly people--a literature review. AB - Implant-supported dentures seem particularly appropriate for the predicament of being elderly and becoming edentulous. The aim of this article was to review the literature on success of dental implants in elderly people. The results of two studies suggested that the treatment with implants can be considered safe and predictable for older as well as for younger patients. Three studies found no increased implant failure-rate in patients with a compromised medical status. Four studies revealed high success-rates of dental implants among groups of elderly people. Within the limitations of this review of the literature it can be concluded that old age does not seem to represent a factor of major prognostic significance in treatment with dental implants. PMID- 11203514 TI - Palliative care dentistry. AB - The importance of dental care is often overlooked due to the omission of the dentist as a member of the palliative care team. However, many terminal patients exhibit oral difficulties that affect their quality of life. Palliative care dentists must exhibit empathy and compassion, and must be excellent communicators Dentists can play an important role in alleviating both the physical and psychological pain of dying. This paper describes the role of dentistry in palliative care. PMID- 11203516 TI - Dental management of patients with Alzheimer's disease and other dementias. PMID- 11203515 TI - Guidelines for oral health care for long-stay patients and residents. AB - People in residential or continuing care have an equal right to good oral health as people residing in the community. Entry to residential or continuing care provides an opportunity to assess need, identify problems, improve oral and dental health thereby contributing to improved general health and quality of life. This document provides guidance to establish standards for oral health care which are appropriate to the needs, demands and choices of individuals whether they live in continuing or residential care (Appendix 5). PMID- 11203517 TI - The influence of storage solution on dentin bond durability of resin cement. AB - OBJECTIVES: This study was conducted to determine the influence of storage solution on the bond durability of three resin cements to bovine dentin over the period of 1 year. METHODS: Ten bovine dentin specimens were tested for shear bond strength with each material (Panavia 21, Kuraray Co.; BISTITE, Tokuyama Co; MASA Bond, Sun Medical Co.) and storage mode, listed below. Four storage environments were studied as follows: water changed every day for 1 year; water unchanged for 1 year; Phosphate Buffered Saline (PBS) changed every week over 1 year; PBS unchanged for 1 year. Ten teeth were also tested for each material at 1 day as a control. The mode of failure was classified after fracture of the bonds by SEM observation. The means of the bond strengths were compared statistically by two way ANOVA and Fisher's PLSD test (p < 0.05). Results for the mode of fracture were analyzed using the Mann-Whitney U test. RESULTS: Although there was no statistical difference in the mean bond strengths between the water and PBS storage solutions (p > 0.05) in all cements, the results for the shear bond strengths in the changed storage solution groups were significantly lower than those where the storage solution remained unchanged (p < 0.05). There were statistical differences between the 1 day results and the changed water groups among all cements (p < 0.05). SIGNIFICANCE: The storage condition influenced the long-term durability of dentin bonding with resin cements. PMID- 11203518 TI - Dentin shear bond strength of compomers and composites. AB - OBJECTIVE: The aim of this study was to compare the shear bond strengths and fracture characteristics of two compomers bonded with a single step bonding agent with two modern composites, a microfil and hybrid, bonded with a fourth generation bonding agent. METHODS: Freshly extracted human third molars were sectioned parallel to the occlusal surface to expose midcoronal dentin, prepared with 320-grit surface finish, and bonded (N = 11 samples/group) following manufacturer's directions with the compomers (Dyract, DeTrey Konstanz, Germany or Compoglass, Vivadent, Schaan Liechtenstein) or the dentin bonding agent SMP+ (Scotchbond Multi-Purpose Plus, 3M Dental Products, St. Paul MN) with Silux Plus or Z100 (3M Dental Products, St. Paul, MN). The samples were tested using a single plane lap shear bond strength test at 5 mm/min until failure. Statistical analysis was performed using ANOVA with Scheffe multiple comparison testing. Fracture surfaces of the debonded surfaces were examined using SEM to determine the failure mode of each specimen. RESULTS: Bond strengths for the compomers were 12.7 +/- 2.9 MPa for Dyract and 8.9 +/- 4.1 MPa for Compoglass and were not significantly different. Bond strengths for the dentin bonded composites were significantly stronger than the compomer Compoglass, but were not different from one another, despite the use of different composites. The averages values for SMP + /Silux Plus and SMP + /Z100 were 15.7 +/- 4.5 MPa and 15.2 +/- 5.6 MPa, respectively. SEM analysis showed that all materials exhibited mixed failure patterns. Compoglass specimens exhibited 5 of 11 failures classified as adhesive, while each of the other materials showed only 1 of 11 adhesive failures. SIGNIFICANCE: Compomers have undergone rapid development over the last several years, but their bond strengths have not yet reached the same level as modern dentin bonded composites. Difference in composite filler type and amount had little influence on the bond strength determined in this work. PMID- 11203519 TI - Quantification of leucite concentration using X-ray diffraction. AB - OBJECTIVES: This study sought to evaluate the efficacy of using an X-ray diffractometer for the determination of leucite in Finesse, Ceramco II, and IPS Empress porcelains. METHODS: An internal standard, copper, was used. Two quantification methods are presented: (1) the generation of a calibration curve using peak height ratios; and (2) the generation of a calibration curve using peak area ratio. RESULTS: The leucite concentration obtained from the peak height versus concentration calibration curve was observed to be statistically different from leucite concentration obtained from the peak area versus concentration calibration curve. Other information obtained from X-ray powder diffraction include the lattice parameters and volume of the unit leucite cell. SIGNIFICANCE: The leucite contained in the dental porcelains (Finesse, Ceramco II, and Empress) has expanded a-lattice spacings and contracted c-lattice spacings relative to standard leucite. These changes in the lattice parameters resulted in a net expansion of the leucite cell volume. PMID- 11203520 TI - The influence of handling technique on the strength of phosphate-bonded investments. AB - OBJECTIVES: This study examined the influence of six handling techniques on the strength of four phosphate-bonded investment (PBI) materials. The size and distribution of pores produced by the handling techniques were investigated and their effect on room temperature strength determined. METHODS: Specimens were tested for strength using four point bend at a cross-head speed of 1 mm min-1. The fracture surface of randomly selected specimens was viewed through a light microscope to determine the pore size. A three-parameter Weibull distribution was used to describe strength giving values of Weibull modulus and characteristic strength. RESULTS: The handling technique that produced the smallest pore size resulted in the highest strength. Significant differences in strength (90% confidence level) were found between most handling techniques. The reduction of pore size by mechanical spatulation and setting under pressure was found to be the most effective method of increasing the strength of PBI. SIGNIFICANCE: Previous studies have related handling technique to the inclusion of air bubbles in dental investments but have not reported any consequent effect on strength. PBI materials are used in production of a range of dental appliances with a variety of different material forming processes and are required to withstand the loads applied without fracture or distortion to ensure accuracy of fit of these prostheses. The use of a handling technique that reduces pore size can significantly increase the strength of PBIs, thereby decreasing the possibility of die fracture or degradation. PMID- 11203521 TI - Mechanical properties and wear behavior of light-cured packable composite resins. AB - OBJECTIVES: Determination of flexural strength, flexural modulus, fracture toughness and wear resistance of three packable composites (Solitaire, Surefil, ALERT) and a packable ormocer (Definite) in comparison with an advanced hybrid composite (Tetric Ceram) and an ion-releasing composite (Ariston pHc). METHODS: Flexural strength, flexural modulus and fracture toughness of each material were determined in three-point bending (each test n = 10). Single-edge notched-bend specimens were used to evaluate the fracture toughness (K1C). Wear of the materials (n = 8) was determined in a pin-on-block-design with a spherical Degusit antagonist at 50 N vertical load and quantified by a replica technique using a 3D-laser scanner. Replicas were made after 6000, 10,000, 30,000 and 50,000 load cycles. The mean wear rate (MWR (micron 3 cycle-1)) was obtained by a linear regression analysis in the steady-state of the time-wear-curve. All results were statistically analyzed with ANOVA and post hoc Tukey HSD tests (p < 0.05). RESULTS: ALERT exhibited the highest flexural modulus (12.5 +/- 2.1 GPa) and K1C (2.3 +/- 0.2 MN m-3/2), but the lowest wear resistance (8275 micron 3 cycle-1). Solitaire presented the highest wear resistance (1591 micron 3 cycle 1), but significantly lower flexural strength (81.6 +/- 10.0 MPa), flexural modulus (4.4 +/- 0.3 GPa), and K1C (1.4 +/- 0.2 MN m-3/2) than all other materials. Surefil revealed a significantly higher flexural modulus (9.3 +/- 0.9 GPa) and wear resistance (3028 micron 3 cycle-1) than Tetric Ceram (6.8 +/- 0.5 GPa; 5417 micron 3 cycle-1) and Ariston pHc (7.3 +/- 0.8 GPa; 7194 micron 3 cycle 1). SIGNIFICANCE: The tested packable composite resins differed significantly in their mechanical properties. This study suggested that fracture and wear behavior of the composite resins are highly influenced by the filler system. Overall, Surefil demonstrated good fracture mechanics parameters and a low wear rate. PMID- 11203522 TI - Depth of cure and compressive strength of dental composites cured with blue light emitting diodes (LEDs). AB - OBJECTIVE: The primary objective of this pilot study was to test the hypotheses that (i) depth of cure and (ii) compressive strength of dental composites cured with either a light emitting diode (LED) based light curing unit (LCU) or a conventional halogen LCU do not differ significantly. The second objective of this study was to characterise irradiance and the emitted light spectra for both LCUs to allow comparisons between the units. METHODS: Dental composite (Spectrum TPH, shades A2 and A4) was cured for 40 s with either a commercial halogen LCU or a LED LCU, respectively. The LED LCU uses 27 blue LEDs as the light source. The composites' depth of cure was measured for 10 samples of 4 mm diameter and 8 mm depth for each shade with a penetrometer. The results were compared using a Student's t-test. Compressive strengths were determined after 6 and 72 h, for six samples of 4 mm diameter and 6 mm depth for each shade after being polymerised for 40 s from each end of the mould. Groups were compared using a three way ANOVA. RESULTS: The conventional halogen LCU cured composites significantly (p < 0.05) deeper (6.40 mm A2, 5.19 mm A4) than did the LED LCU (5.33 mm A2, 4.27 mm A4). Both units cured the composite deeper than required by both ISO 4049 and the manufacturer. A three way ANOVA showed that there were no significant differences in the compressive strengths of samples produced with either the LED LCU or the halogen LCU (p = 0.460). Significant differences in compressive strength of samples stored for 6 and 72 h (p = 0.0006) and of samples of different shades (p = 0.035) were found as confirmed by the three way ANOVA. The light spectra of both units differed strongly. While the halogen LCU showed a broad distribution of wavelengths with a power peak at 497 nm, the LED LCU emitted most of the generated light at 465 nm. The LED LCU produced a total irradiance of 350 mW cm-2 whereas the halogen LCU produced a total irradiance of 755 mW cm-2. SIGNIFICANCE: The results showed that both units provided sufficient output to exceed minimum requirements in terms of composites' depth of cure according to ISO 4049 and the depth of cure and the composites' compressive strength stated by the manufacturer. Compressive strengths of dental composites cured under laboratory conditions with a LED LCU were statistically equivalent to those cured with a conventional halogen LCU. With its inherent advantages, such as a constant power output over the lifetime of the diodes, LED LCUs have great potential to achieve a clinically consistent quality of composite cure. PMID- 11203523 TI - Nanoleakage patterns of four dentin bonding systems. AB - OBJECTIVES: The purpose of this study was to evaluate the nanoleakage patterns of four dentin bonding systems. METHODS: The dentin bonding systems used in this study were: Single Bond, One Coat Bond, Prime & Bond NT/Non Rinse Conditioner (NRC), and PermaQuik. Flat occlusal dentin surfaces from extracted human molars were finished with wet 600-grit silicon carbide paper, and bonded with one of the dentin bonding systems. After 24 h storage at 37 degrees C in water, margins were finished with polishing discs and the surrounding tooth surfaces coated with nail varnish. The samples were immersed in a 50% (w/v) solution of silver nitrate for 24 h, and exposed to photodeveloping solution for 8 h. The samples were cut longitudinally, polished, and mounted on stubs, carbon coated and observed in a Field Emission-SEM using backscattered electron mode. RESULTS: Different nanoleakage patterns were observed with the different adhesive systems. However, accumulations of silver particles were often noted at the base of the hybrid layer for all materials. Single Bond and One Coat Bond demonstrated uptake of silver particles both within the hybrid layer and the adhesive resin. Prime & Bond NT/NRC showed silver staining throughout almost the entire thickness of the hybrid layer. The leakage pattern of PermaQuik revealed loose silver deposition within the hybrid layer. The composition of each adhesive system may play a role in forming the different leakage patterns. SIGNIFICANCE: The current dentin bonding systems used in this study do not achieve perfect sealing at the restoration/dentin interface, which may influence the durability of the bond to dentin. PMID- 11203524 TI - Corrosion susceptibility of titanium covered by dental cements. AB - OBJECTIVES: The aim of this study is to determine the influence of acidic fluorinated cements (as glass ionomer (GI) cements) on the passivation of titanium, using electrochemical investigations. METHODS: We realized experimental electrodes that associate titanium and dental cements. Polarization resistance of titanium electrodes has been determined for uncovered metal and electrodes covered with three dental cements. Student's t-tests proved the reproducibility. We also compared successive voltammograms for uncovered titanium and GI covered titanium. RESULTS: Correct passivation was observed with zinc eugenate, but fluorinated GI or zinc phosphate coverage increased the corrosion susceptibility. SIGNIFICANCE: However there is no evidence of titanium depassivation when covered with cement. No clinical contraindication can be held. PMID- 11203525 TI - The effects of alcoholic beverages on composite wear. AB - OBJECTIVES: In vivo wear of composite restorative materials appears to be, in part, dependent on various patient factors. Specifically, consumption of alcoholic beverages has the potential for increasing the degradation rate. The hypothesis tested in this experiment was that composite wear is dependent on the type of alcohol-containing liquid the materials are exposed to during three-body abrasive wear. METHODS: To test this hypothesis, composite wear experiments were performed using the ACTA three-body wear machine. Abrasive slurries containing either beer, wine, 9 vol% ethanol or water were used during the wear experiments. The data were analyzed using ANOVA and Tukey's test. RESULTS: The wine and ethanol solutions caused significantly more wear compared to the beer and water. There was no significant differences in the wear between the wine and 9 vol% ethanol groups, and the beer groups were not significantly different from the water groups. Furthermore, there was no significant interaction between the composite type and the various abrasive slurries. SIGNIFICANCE: These results indicate that alcoholic beverages with at least 9 vol% ethanol will increase the wear of composite. The observed increase in wear of composite by the wine was caused primarily by the ethanol content of the wine. Other constituents in the wine do not appear to have an effect on composite wear. The ethanol effect was consistent among different composite types. PMID- 11203526 TI - Interface dimensions of CEREC-2 MOD inlays. AB - OBJECTIVES: To quantify the width of the cement interface between ceramic inlays generated by the CEREC-2 CAD-CAM system and the tooth, and to determine the effect of cement viscosity on the interface width. METHODS: Standardised MOD cavities were cut in 15 human premolar teeth using a custom paralleling device. A ceramic inlay was made with a CEREC-2 CAD-CAM machine for each tooth. The inlays were cemented using one of three resin-based composite systems of varying viscosity; a hybrid microfilled posterior composite, a compomer restorative and a dual-cure luting composite. The teeth were subsequently sectioned and measurements were taken at 21 key points with the aid of an image-analysis light microscopy system. RESULTS: Statistical significance tests were applied to examine for difference in interface dimensions at specific points within each of the cement-groups and amongst groups. The interface space at the occlusal walls has a distinct wedge shape, being narrower at the external interface (50 microns, SD 15) than internally (211 microns, SD 38). There is no statistically significant difference in the interface dimensions of the gingival floor between the boxes that lie above and below the CEJ. There is no statistically significant difference in the width of the interface at any given point between the three cement groups. SIGNIFICANCE: There is a significant improvement in the fit of CEREC-2 restorations when compared with the original CEREC system. Cements of varying viscosity (within the measured range) may be used for cementation of these inlays, without adversely affecting the width of the interface. Caution must be exercised with light-activated composite cements to ensure adequate transmission of light through the ceramic and the underlying composite cement. PMID- 11203527 TI - Permeability of demineralized dentin to HEMA. AB - OBJECTIVES: The objectives of this study were to develop a macromodel of the demineralized layer of dentin that is formed after acid-etching, and to determine if the amount of HEMA uptake was responsive to air drying. The hypothesis that was tested was that HEMA uptake by demineralized dentin depends upon the degree of expansion of the collagen fibril network. METHODS: Dentin cubes (2 x 2 x 2 mm) were prepared in coronal dentin from extracted unerupted human third molars. They were incubated in 100% HEMA for up to 1000 min and then removed and blotted free of excess adherent HEMA. The HEMA taken up by each cube was extracted in 2 ml of water for 1 hr with shaking. This was repeated and the extracts combined. HEMA was quantitated spectrophometrically. The dentin cubes were then demineralized in 0.5 M EDTA for 10 days and the HEMA uptake remeasured at 1, 10, 100 and 1000 min. Then the cubes were air-dried and the HEMA uptake remeasured. After re-expanding the specimens in water, the cubes were stiffened in ascending concentrations of acetone of 100%, then allowed to air dry again in a more expanded state, and HEMA uptake was remeasured. Finally, after rehydration, the dentin cubes were "acid etched" for 1 or 10 min with 37 wt% phosphoric acid and HEMA uptake remeasured. RESULTS: Before demineralization, the dentin took up little HEMA (ca. 4.8 x 10( 7) moles min-3) compared to after demineralization when the uptake for 10, 100 and 1000 min was 27.4, 43.8 and 51.4 x 10(-3) moles mm-3, respectively. Acid etching for 1 or 10 min had no effect on HEMA uptake. Air drying produced a 72% volumetric shrinkage but a 97% reduction in uptake. When the demineralized matrix was stiffened in acetone prior to air-drying, the volumetric shrinkage was only 27% and the HEMA uptake only fell 16% compared to the wet, fully expanded condition. SIGNIFICANCE: The results support the hypothesis that the uptake of HEMA by demineralized dentin depends on the degree of expansion of the dentin matrix. PMID- 11203528 TI - Effect of Pd or Au addition on age-hardening in AgMn-based alloys. AB - OBJECTIVE: The objective of this research was to characterize the age-hardening behavior of AgMn alloys modified with Au or Pd. These alloys are being studied as possible alternatives to Type III dental alloys. METHODS: The age-hardening reactions in Ag-37 at % Mn alloys with 5 at% Au or Pd were investigated by optical microscopy, electrical resistivity, X-ray diffraction and hardness tests. RESULTS: Optical microscopy showed no grain boundary precipitates formed after overaging. The maximum hardness reached by aging in all alloys is about 260 (Hv) and identical to that of traditional AgPdCu dental alloys. The precipitation reactions were retarded with the addition of 5 at% Au or Pd. X-ray diffraction studies suggest a fine precipitate, alpha-Mn, is dispersed within the grain interior. The activation energy for the precipitation reaction is 114 kJ/mol for the AgMn and AgMnAu alloys. This value is about one-half of the activation energy for volume diffusion of manganese in AgMn alloys. SIGNIFICANCE: The age hardenable AgMn-based alloys modified with Au or Pd can achieve hardness values comparable to those of traditional AgPdCu alloys. Provided the in vivo corrosion resistance of these alloys is adequate, they show promise as a Cu-free alternative material for cast restorations. PMID- 11203529 TI - Materials, the millennium and the mind of God. PMID- 11203530 TI - Inhibition of human gingival gelatinases (MMP-2 and MMP-9) by metal salts. AB - OBJECTIVES: The interaction between metal ions and the oral environment is a major subject matter in dental research. Matrix metalloproteinases (MMPs) have been implicated in several pathologic oral processes such as periodontal tissue destruction, root caries, tumour invasion and temporomandibular joint disorders. The aim of this work was to test the effect of Zn, Cu, Sn and Hg ions on the activity of the major gingival gelatinolytic MMPs. METHODS: Gingival explants were cultured overnight in DMEM and the activity of secreted enzymes was analyzed by gelatin zymography in buffers containing different metal ion concentrations. The major gelatinolytic proteinases present in the conditioned media were characterized as MMP-2 and MMP-9 by immunoprecipitation with specific antibodies. The eletrophoretic bands were scanned and the transmittance values were analyzed with the Sigmagel software (Sigma). RESULTS: ZnSO4 was a strong inhibitor of MMP 2 (I50 = 15 microM) and MMP-9 (I50 = 40 microM), whereas CuSO4, HgSO4 and SnCl2 showed less efficient inhibition potential. SIGNIFICANCE: Our findings show that the activity of oral tissue MMPs may be modulated by metal ions present in the oral environment. Therefore, the accumulation of metals in connective tissue may interfere with the formation and resorption of the extracellular matrix components. PMID- 11203531 TI - Improving the processing of high-gold metal-ceramic frameworks by a pre-firing heat treatment. AB - OBJECTIVES: High-gold metal-ceramic alloys are difficult to elaborate due to their soft surface. Overlappings after grinding cause porosities at the metal ceramic interface. Poor mechanical strength at high temperatures leads to thermal distortion of the framework. During firing hardness and high temperature strength of the alloy improve, thus improving processing. Therefore the question arises if by a pre-firing heat treatment hardening can be anticipated without affecting the mechanical strength after firing. METHODS: Four commercially available alloys were investigated with regard to hardness, thermal distortion, proof stress, and grain growth in the as-cast state, after a pre-firing heat treatment at 950 degrees C for 10 min, after a complete firing cycle and after a combination of both heat treatments. Hardness was measured as HV5/30, thermal distortion by means of a three point bending test and proof stress according to ISO 9693: 1991. The results were compared by means of Student's t-test (p < 0.05). RESULTS: For all alloys hardness, resistance to thermal distortion, and proof stress significantly increased after the pre-firing heat treatment compared to the as cast state. When a pre-firing heat treatment was performed before the complete firing cycle, hardness may slightly drop, but proof stress and resistance to thermal distortion remained at least constant or even improved, compared to the results obtained after a complete firing cycle. Grain growth due to the pre firing heat treatment was not observed. SIGNIFICANCE: The results showed, that a heat treatment of high-gold frameworks performed directly after casting improves processing without affecting mechanical strength. PMID- 11203532 TI - An assessment of the influence of mixing induced variability on the bi-axial flexure strength of dentine porcelain discs and the implications for laboratory testing of porcelain specimens. AB - OBJECTIVES: The proportions of dentine powder and modelling fluid employed to produce a "creamy" porcelain slurry consistency used in veneer construction are assessed by the technical experience of the operator so that variability is inevitable. The present study investigated the implications of mixing variability on the slurry consistency used in the manufacture of dentine porcelain disc specimens for laboratory testing. METHODS: Vitadur-Alpha dentine porcelain was fabricated into disc specimens and the mean fracture strength, standard deviation and associated Weibull Moduli (m) were determined by fracturing sets of 30 specimens prepared to different powder contents for a constant 0.33 ml of liquid using bi-axial flexure (ball-on-ring). RESULTS: The strength data showed variation in magnitude and consistency ranging from 85.1 +/- 12.9 MPa (m = 7.2 +/ 1.3) at 0.82 g to 87.3 +/- 11.9 MPa (m = 8.0 +/- 1.5) at 0.91 g and 81.9 +/- 13.2 MPa (m = 6.7 +/- 1.2) at 1.0 g of powder. Increasing or decreasing the powder content of the slurry (compared with specimens condensed using 0.91 g of powder) resulted in an increase in porosity and a decrease in the apparent solid density. SIGNIFICANCE: No significant decrease in the mean bi-axial flexure strength or reliability of the fracture strength data was identified for the slurry consistencies investigated, however, the results suggested that an optimum consistency existed wherein consistent reproducibility of test results was achieved. A comparison between materials can only be achieved if specimen preparation occurs consistently between test centres and therefore these results appear to have implications for the laboratory testing of materials. PMID- 11203533 TI - Improved reliability of leucite reinforced glass by ion exchange. AB - OBJECTIVES: The aim of this study was to develop an adequate process-, proof- and calculation technique for the chemical strengthening of dental ceramic materials in order to evaluate the efficiency of this method from the engineering point of view. METHODS: Ion exchange examinations below glass temperature have been done for the dental all ceramic system IPS-Empress (Ivoclar). In addition experiments on specimens were undertaken, which were stored in artificial saliva for the period of one month after the ion exchange treatment. The efficiency of the ion exchange treatments has been evaluated based on the chemical composition of the surface layer, the residual stress distribution, the flexural- and the burst strength and surface hardness. In addition, Weibull statistical analysis of the four-point bending and burst test data provides new information about the failure mechanisms of chemically strengthened dental ceramics. RESULTS: The ion-exchange process with a potassium salt increases the reliability of the dental ceramic material "IPS-Empress". By the KNO3 or Tuf-Coat ion exchange treatment potassium ions will be implanted as clusters directly into the crystal lattice which results in an increase of the binding energy and hence, in a pronounced increase in the surface hardness. In particular the stress bearing capabilities of dental all ceramic restorations, which are subject to high bending stresses, i.e. dental crowns and dental bridges, are largely improved by the induced residual stresses. This increase of residual stresses did not relax significantly after a one month storage in artificial saliva. SIGNIFICANCE: Enhanced load limits and a more narrow strength distribution spectrum is considered desirable for increasing the clinical longevity of all ceramics. PMID- 11203534 TI - Mechanical properties and microstructures of glass-ionomer cements. AB - OBJECTIVE: The objective of this study was to determine the flexural strength (FS), compressive strength (CS), diametral tensile strength (DTS), Knoop hardness (KHN) and wear resistance of ten commercial glass-ionomer cements (GICs). The fracture surfaces of these cements were examined using scanning electron microscopic (SEM) techniques to ascertain relationships between the mechanical properties and microstructures of these cements. METHODS: Specimens were fabricated according to the instructions from each manufacturer. The FS, CS, DTS, KHN and wear rate were measured after conditioning the specimens for 7 d in distilled water at 37 degrees C. One-way analysis of variance with the post hoc Tukey-Kramer multiple range test was used to determine which specimen groups were significantly different for each test. The fracture surface of one representative specimen of each GIC from the FS tests was examined using a scanning electron microscope. RESULTS: The resin-modified GICs (RM GICs) exhibited much higher FS and DTS, not generally higher CS, often lower Knoop hardness and generally lower wear resistance, compared to the conventional GICs (C GICs). Vitremer (3M) had the highest values of FS and DTS; Fuji II LC (GC International) and Ketac-Molar (ESPE) had the highest CS; Ketac-Fil (ESPE) had the highest KHN. Ketac-Bond (ESPE) had the lowest FS; alpha-Silver (DMG-Hamburg) had the lowest CS. Four GICs (alpha-Fil (DMG-Hamburg), alpha-Silver, Ketac-Bond and Fuji II) had the lowest values of DTS, which were not significantly different from each other; alpha Silver and Ketac-Silver had the lowest values of KHN. The highest wear resistance was exhibited by alpha-Silver and Ketac-Fil; F2LC had the lowest wear resistance. The C GICs exhibited brittle behavior, whereas the RM GICs underwent substantial plastic deformation in compression. The more integrated the microstructure, the higher were the FS and DTS. Higher CS was correlated with smaller glass particles, and higher KHN was found where there was a combination of smaller glass particles and lower porosity. Larger glass particle sizes and a more integrated microstructure contributed to a higher wear resistance. SIGNIFICANCE: The mechanical properties of GICs were closely related to their microstructures. Factors such as the integrity of the interface between the glass particles and the polymer matrix, the particle size, and the number and size of voids have important roles in determining the mechanical properties. PMID- 11203535 TI - The permeability of dental procedure and examination gloves by an alcohol based disinfectant. AB - OBJECTIVES: The usage of gloves in dentistry has increased greatly over the last 10 years and this has highlighted certain problems when gloves are being worn extensively. While skin irritations and allergies caused by latex proteins and accelerators have been the main focus of attention, dental materials such as disinfectants have also become known as a source of skin reactions. This study was performed to evaluate the permeability of various gloves by ethanol. METHODS: The tip of the middle finger of 13 glove brands (natural latex gloves (NLG) powdered or unpowdered, powdered vinyl, nitrile and synthetic elastomer) was exposed to 5 ml of a hand disinfectant (Desderman). After a penetration time ranging from 2 min to 8 h the permeation of Desderman was detected with a gas chromatograph. RESULTS: Only one component of the disinfectant (ethanol) could be detected to have gone through the gloves. After only 2 min the vinyl and one nitrile glove and after 10 min all glove types were permeated. Powder seemed to have no real influence on the penetration of ethanol. Some natural latex gloves showed a low rate of leakage, while vinyl and nitrile gloves were penetrated quickly and to a great extent. The synthetic elastomer (Biogel Neotech) was the only one with a significantly lower penetration even after 2-8 h. SIGNIFICANCE: While there are reports of adverse skin reactions to alcohol the amount of ethanol (up to 40 microliters after 2 h) detected in this study is much too low to cause irritations and certainly not toxicity, but it could possibly initiate allergic reactions. PMID- 11203536 TI - Dimensional changes and pressure of dental stones set in silicone rubber impressions. AB - OBJECTIVES: A high expansion stone has been used for improving the adaptation of dentures. Although the method is based on the idea to compensate for the processing shrinkage of the denture base resin with the high expansion stone, there are few studies on the expansion behavior of stones in an impression. The purpose of this study is to clarify the dimensional changes of stones set in silicone rubber impressions using two types of impression tray. METHODS: Impressions of a master model that represents the alveolar ridge were taken using a silicone impression material and the dimensional changes in the stone casts were measured in different directions (x, y and z-axes). Two types of impression tray were used, one with an open surface and the other with a closed surface. In order to evaluate the setting expansion of the stones and the pressure against the impression, stones were poured in other impressions that were taken from a cubic master model. The thickness of the impression was set at 2 mm. RESULTS: A statistical analysis showed that there were significant differences in the dimensional change in the vertical direction (z-axis) and horizontal directions (x- and y-axes) of any stone casts set in the open tray. However, there were no significant differences in the dimensional changes in any direction of each stone cast set in the closed tray. SIGNIFICANCE: The impression tray influences the setting expansion of stones. Stones do not uniformly expand in the open tray and the dimensional changes in the stone casts in the three-dimensions increases, when used with a high expansion stone. PMID- 11203537 TI - Flexural properties and impact strength of denture base polymer reinforced with woven glass fibers. AB - OBJECTIVES: The present investigation was undertaken to determine the reinforcing effect of woven glass fibers on deflection, flexural strength, flexural modulus and impact strength of acrylic denture base polymer. METHODS: Three silanized or unsilanized woven glass fibers were used. Specimens were made by heating the denture cure resin dough containing glass fibers, which were sheathed in the dough. Specimens with four different thicknesses and of five different types were made, incorporating the glass fiber. Three-point flexural test and flywheel type impact test were employed to determine the flexural properties and impact strength. RESULTS: When specimens contained unsilanized glass fiber, the flexural strength in specimens of 1 and 2 mm thickness and the impact strength in specimens of 2 mm thickness were higher than those of specimens without glass fiber (p < 0.01). On the contrary, the flexural strength and deflection in specimens reinforced with silanized glass fiber of 1 mm thickness were significantly higher (p < 0.01, p < 0.05) than those of unreinforced specimens. Further, the impact strength in specimens reinforced with silanized glass fiber of 2 mm thickness was significantly higher (p < 0.01) than that of unreinforced specimens. Statistically significant differences were found in the flexural strength (p < 0.05) and in the impact strength (p < 0.01) when specimens of 4 mm thickness were reinforced with two or three unsilanized glass fibers. SIGNIFICANCE: The reinforcement with glass fiber was effective in thin specimens, and the reinforcing effect increased with the increase of the number of glass fibers in the case of thick specimens. PMID- 11203538 TI - High pressure liquid chromatography of dentin primers and bonding agents. AB - OBJECTIVE: The purpose of this study was to analyse the composition of representative dentin primers and bonding agents, and to investigate the relationship between chromatographic retention times and partition coefficient (log P) values. METHODS: Dentin bonding systems (DBS) were analysed with reversed phase high-performance liquid chromatography (HPLC). The log P values were obtained computationally with the advanced chemistry development software. RESULTS: The DBS were analysed and the monomers were identified. The log P values were calculated and the relationship between log P and retention times for the monomers was described by the equation: log P = 2.436R(t) - 3.636, with a correlation value (r) of r = 0.9095. SIGNIFICANCE: The components of the DBS were successfully resolved and identified, thus illustrating the analytical power of HPLC regarding those systems. Also the log P values correlated with the retention times of monomers. Thus, they can be used as a prediction tool in future analysis. These findings are important for a mechanistic understanding of Primer and Adhesive actions in the bonding to the dentin. PMID- 11203539 TI - Dimensional changes of resin/ionomer restoratives in aqueous and neutral media. AB - OBJECTIVES: The aim was to study dimensional time-dependence of resin/ionomer formulations from 5 min age to one month and to separate out the intrinsic setting shrinkage and hygroscopic expansion effects, by using non-aqueous and aqueous storage media, respectively. METHODS: Materials studied included: A: resin-, B: metal- and C: polyphosphonate-modified glass-ionomer cements [GICs]; and controls of D: poly-acid modified composite [compomer]; and E: resin composite. Separate specimen groups (n = 5) were stored in different storage media: (i) silicone fluid; (ii) de-ionized water. Experiments were repeated at 23 and 37 degrees C. Volumetric changes of specimens (4 mm diameter x 6 mm height) were obtained via accurate mass measurements (to 10(-4) g), using Archimedes principle, with silicone or water also used as the Archimedean fluid. These measurements were made periodically over a 30 day period, post fabrication. RESULTS: In silicone at 23 degrees C, all materials underwent further gradual intrinsic shrinkage (after 5 min from mix). This was highly significant (p < 0.05) for the RM-GIC (A). At 37 degrees C, however the RM-GIC expanded, indicating that its cure is temperature-sensitive. In water, at 23 and 37 degrees C, the shrinkage was either partially offset (materials C, D, E), or replaced by appreciable expansions (materials A and B). Differences between RM-GIC (A) and MM GIC (B) were significant (p < 0.05). SIGNIFICANCE: The deployment of dual storage media made an important contribution to the separate analysis of the volumetric changes due to the on-going setting chemistry in these systems and the time dependent effects of an aqueous environment. PMID- 11203540 TI - Long-term corrosion of a Ga-containing restorative material. AB - OBJECTIVE: The aim was to simulate and characterize the long-term corrosion of a Ga-containing alloy (Galloy, SDI). METHODS: To induce corrosion, cylindrical specimens, 8 x 4 mm, of the material were subject to potentiostatic polarization at -0.1 V (SCE) in a phosphated buffered saline (PBS) solution at 20 degrees C for d. The current-time transients during polarization were recorded and the corresponding anodic charge, Q, was calculated. Parallel potentiostatic corrosion tests in a Cl-free PBS solution were also conducted to demonstrate the significance of the Cl- ion in corrosion. In addition, potentiodynamic anodic polarization tests were performed to characterize the overall corrosion behavior of the alloy in both electrolytes. The external and internal corroded layers, formed during potentiostatic corrosion in PBS, were measured by optical microscopy. SEM and EDXA were used to characterize the morphology and composition of the potentiostatically polarized surfaces. RESULTS: Galloy was passive in Cl free PBS. The Cl- ion in PBS destroyed passivity and initiated a "dissolution precipitation" type reaction during potentiostatic corrosion. The latter led to circumferential internal corrosion and growth of a layer of external corrosion products. The thickness of the internal and external corrosion layers was 0.77 +/ 0.07 and 0.86 +/- 0.37 mm, respectively. The Q value (89.3 +/- 13.7 C/cm2) in PBS was about two orders of magnitude higher than that (0.66 +/- 0.24 C/cm2) in Cl-free PBS. The corrosion products contained Sn, Ga, In, Cu, O and Cl. SIGNIFICANCE: Massive internal and external corrosion in a Cl-containing medium as in saliva, accumulation of corrosion products at the cavity wall, and the consequent stress build-up contribute to post-operative pain, tooth straining, marginal breakdown and fractured teeth reported with the clinical use of Galloy. PMID- 11203542 TI - Measurements from digital panoramic radiographs. PMID- 11203541 TI - Comparison of microscopy and radiography as gold standards in radiographic caries diagnosis. PMID- 11203543 TI - Susuks. PMID- 11203544 TI - Stability of the mucosal topography around single-tooth implants and adjacent teeth: 1-year results. AB - This study evaluated the soft tissue stability around 10 single-tooth implants. All cases were treated following the same protocol, which included guided bone regeneration and connective tissue grafting. One year after prosthesis insertion the soft tissue shrinkage on the buccal side of the implant crown was 0.6 mm on average. The soft tissue volume in the papilla area increased on average by 0.375 mm, and none of the papillae lost volume. PMID- 11203545 TI - Human histologic evaluation of a bovine-derived bone xenograft in the treatment of periodontal osseous defects. AB - This study evaluated a bovine-derived bone xenograft (Bio-Oss) in the treatment of human periodontal osseous defects. Four patients with at least one tooth that had been recommended for extraction because of interproximal advanced periodontal disease volunteered to participate. The surgical procedure consisted of flap reflection, soft tissue debridement, placing a notch in calculus as a histologic reference point, root planing, placement of the bovine-derived xenograft and a bioresorbable physical barrier, and flap closure. Patients were seen every 2 weeks for plaque control and any necessary adjunctive treatment. At 4 to 6 months postsurgery, 6 teeth, along with the adjacent graft site, were removed en bloc. Histologic observations demonstrated new bone, new cementum, and new periodontal ligament coronal to the reference notch in 3 of the 4 specimens. This study indicates that periodontal regeneration is possible following grafting with a bovine-derived xenograft. PMID- 11203546 TI - Orthodontic treatment in periodontally compromised patients: 12-year report. AB - This work describes the therapeutic protocol of combined orthodontic-periodontal treatment and evaluates the effectiveness of surgical and nonsurgical periodontal therapy in the maintenance of a healthy periodontal status after the orthodontic treatment. Surgical periodontal treatment was performed in 267 patients affected by severe periodontal disease, and 128 patients had nonsurgical treatment. For each patient the mean value of probing depth (mPPD) and the rate of positive bleeding on probing (%BoP) of the teeth involved in the orthodontic movement were registered before the start of the periodontal treatment, at the end of the orthodontic treatment, and 2, 4, 6, 10, and 12 years after the end of the orthodontic treatment. Comparison between pretreatment and posttreatment values and between pretreatment and follow-up values showed a decrease in mPPD and %BoP that was of statistical significance. The difference between posttreatment and follow-up values was not statistically significant. These results suggest that orthodontic treatment is no longer a contraindication in the therapy of severe adult periodontitis. In these cases orthodontics improve the possibilities of saving and restoring a deteriorated dentition. PMID- 11203547 TI - Tissue regeneration in bone defects adjacent to endosseous implants: an experimental pilot study. AB - Extraction socket defects or alveolar ridge defects may limit or restrict placement of implants. The present study assessed the efficacy of inducing bone formation with demineralized freeze-dried bone (DFDB), osteoinduction with hydroxyapatite (HA), and guided bone regeneration with expanded polytetrafluoroethylene (e-PTFE) in bone defects adjacent to endosseous implants in an animal model. Twenty-four implants were placed in the long bones of 3 pigs. After preparation of 24 cylindric acute defects adjacent to the coronal 5 mm of each implant, 18 of the defects were treated by DFDB, HA, or e-PTFE. The 6 remaining defects healed spontaneously with no treatment (controls). In each pig, one tibia received 4 commercially pure titanium screw implants (3.75 mm x 15 mm), while the contralateral tibia received 4 HA-coated cylindric implants (3.25 mm x 15 mm). Bone formation in response to the 3 treatments and control cases was evaluated using computer-assisted densitometric image analysis. The results showed that a higher density of tissue formed under e-PTFE membranes. A significantly greater increase in bone density was noticed in bone defects treated with an e-PTFE membrane vs DFDB (P = 0.04), in e-PTFE vs control sites (P = 0.04), and in defects treated with HA vs DFDB (P = 0.04) in HA-coated implants. In titanium implants the differences observed were not significant. It was also observed that bone regeneration in defects treated with HA differs with the type of implant used (titanium vs HA-coated implants), but such differences were not significant. PMID- 11203548 TI - A comparative study of root coverage obtained with an acellular dermal matrix versus a connective tissue graft: results of 107 recession defects in 50 consecutively treated patients. AB - Obtaining root coverage has become an important part of periodontal therapy. In this study, 2 surgical root coverage procedures were examined. The control group was treated with a coronally positioned pedicle graft combined with a connective tissue graft. The test group was treated with a coronally positioned pedicle graft combined with an acellular dermal matrix. There was no statistically significant difference in the mean root coverage obtained (96.2% control vs 95.8% test). There was a statistically significant reduction in probing depth (1.2 mm control vs 0.7 mm test) and increase in keratinized tissue (2.0 mm control vs 1.2 mm test) in both groups. The connective tissue graft produced a greater mean probing reduction and mean keratinized tissue increase than the acellular dermal matrix. However, this did not appear to be clinically significant. The results of both procedures were esthetically acceptable to the patients and clinically acceptable in all cases. In this study, the acellular dermal matrix and the connective tissue graft resulted in similar amounts of root coverage. PMID- 11203549 TI - Periodontal medicine in the next millennium. PMID- 11203550 TI - The use of demineralized freeze-dried bone-glycoprotein matrix grafts in treating baboon periodontal infrabony defects. AB - In an effort to improve regenerative capacity and establish higher levels of predictability, the use of a new graft material was investigated in baboon infrabony periodontal defects. A graft matrix composed of human demineralized freeze-dried bone combined with human connective tissue glycoprotein was implanted in 20 defects in 9 baboons. Control, debrided-only sites in the same animal served as a comparison. Grafted sites achieved a 1.8-mm greater reduction in probing depth and attachment gain compared to controls. In addition, 25.3% greater defect fill was found in grafted sites. Histologic analyses provided evidence of bone induction by the graft matrix and regeneration of new cementum, periodontal ligament, and bone in the grafted sites. PMID- 11203551 TI - Immediately loaded mandibular implant bar overdenture: a surgical and prosthodontic rationale. AB - Classical guidelines for osseointegration include a long healing time, during which functional load should be avoided. However, the long healing period might impose an intolerable situation on some patients, especially in the completely edentulous situation. Studies on immediately loaded implant-supported prostheses in completely edentulous patients have been reported, exhibiting high success rates comparable to conventionally loaded implants. This article describes the surgical and prosthodontic procedure for the immediately loaded mandibular implant bar overdenture as well as its clinical rationale. PMID- 11203552 TI - Ceramic abutments--a new era in achieving optimal esthetics in implant dentistry. AB - In the visible dental region in particular, implant-prosthetic restorations filling single-tooth gaps make exacting demands on function and esthetics. One crucial factor influencing the esthetic outcome is the emergence profile of the restoration. The introduction of aluminum oxide or zirconium oxide abutments, which can be milled to meet individual requirements, provides new opportunities for reconstruction adapted to anatomic findings. Tooth-matched coloring combined with customized preparation and dimensioning make for optimal mucogingival esthetics in implant-supported single-tooth restorations. The aim of the present article is to give a general survey and to illustrate the use of ceramic abutments with clinical case reports. PMID- 11203553 TI - The influence of sulfate-reducing bacteria colonization of 2 different bioresorbable barrier membranes for GTR. An 18-month case-controlled microbiologic and clinical study. AB - The purpose of the present microbiologic and case-controlled clinical study was to examine the colonization of 2 different resorbable barrier membranes by sulfate-reducing bacteria (SRB). The barrier membranes tested were Guidor matrix barrier and Resolut regenerative material. Ten patients exhibiting 3 Class II furcation defects and 7 intrabony defects were included in the study. The probing depth and the clinical attachment level at 4 surfaces per tooth were taken at the beginning of the study. Microbiologic samples were taken from the experimental sites and from the approximal sites of the adjacent teeth. Both types of resorbable membranes were positive for SRB colonization. The detection of SRB in 2 of 7 intrabony defects and in all defects with furcation involvement before the membrane placement indicated that these organisms are a common inhabitant of sites showing periodontal destruction and are associated with guided tissue regeneration (GTR). According to the clinical criteria for healing tendencies used in this study, the GTR procedures were less successful in the presence of SRB. There were no significant clinical effects of different resorbable membrane materials or membrane layout on attachment level changes for either the intrabony defect or furcation groups after 18 months. There were no statistical differences for sites that became exposed to SRB when compared to sites that remained unexposed after 18 months. The numeric significance of SRB in relation to the total microbial count needs to be determined to gain insight into the ecologic role of membrane resorption rates. PMID- 11203554 TI - Histologic and clinical comparison of bilateral sinus floor elevations with and without barrier membrane placement in 12 patients: Part 3 of an ongoing prospective study. AB - In 1993 the Department of Implant Dentistry at New York University College of Dentistry began a long-term clinical, histologic, histomorphometric, and radiographic study of the sinus elevation procedure. One of the parameters under evaluation in this study is the effect of barrier membrane placement on the creation of vital bone in the grafted sinus cavity. This report presents a histologic and histomorphometric evaluation of healing with and without the placement of an expanded polytetrafluoroethylene (e-PTFE) barrier membrane over the lateral window at the time of sinus grafting. The data were collected from 12 patients who underwent bilateral sinus elevation surgery. In each of these 12 patients the same grafting material was used in both sinuses, making the presence or absence of an e-PTFE barrier membrane the only controlled variable. Under the conditions of this study, the results indicate that (1) placement of the barrier membrane tends to increase vital bone formation; (2) placement of a barrier membrane has a positive effect on implant survival; and (3) membrane placement should be considered for all sinus elevation procedures. PMID- 11203555 TI - A case report study of 72 consecutive Emdogain-treated intrabony periodontal defects: clinical and radiographic findings after 1 year. AB - This case report study examined the effect of adjunctive use of Emdogain in the treatment of intrabony periodontal defects. Seventy-two consecutively treated defects in sixty-one patients were included. Efficacy of treatment was evaluated at 12 months by assessment of probing depth reduction, probing attachment level gain, and radiographic bone gain from standardized radiographs. Initial pocket depth averaged 8.3 mm, and the mean probing attachment level was 10.0 mm. The mean radiographic defect depth was 5.3 mm. At 12 months, mean pocket depth reduction was 4.7 mm and mean probing attachment level gain was 4.2 mm. Radiographic bone level gain averaged 3.1 mm and defect fill averaged 70%. The only variables significantly affecting radiographic bone gain were bleeding on probing and smoking. It was concluded that Emdogain treatment of one- and two walled intrabony defects in a periodontal practice will result in a clinically significant gain of probing attachment level and radiographic bone that is similar to that reported in controlled clinical trials. PMID- 11203556 TI - Soft tissue management around implants in the esthetic zone. AB - The concept of overbuilding the implant site in the esthetic zone is paramount in creating the inconspicuous implant restoration. If teeth are congenitally missing, the site may be underdeveloped. Tooth extraction and trauma may lead to ridge deformities. The goal is to create an enhanced site for the restorative clinician. This site can then be molded to an ideal gingival framework. Cases are used to illustrate surgical and orthodontic techniques for preserving and overbuilding the implant site in the esthetic zone. PMID- 11203557 TI - The Procera AllCeram system. AB - The Procera AllCeram system is indicated for manufacturing all-ceramic crowns for single-tooth restorations in the anterior and posterior regions. In addition, it is possible to create metal-free superstructures on CeraOne abutments from the Branemark implant system or crowns on individually prepared aluminum oxide abutments (CerAdapt). The Procera copings, which are manufactured using computer aided design/manufacturing technology, are characterized by very good mechanical properties. Ceramic veneers tailored to the copings offer excellent esthetics, favorable abrasion behavior, and an ideal surface structure for non-inflammatory apposition of the periodontal or periimplant tissues. The present article offers an overview of previous scientific studies, describes clinical and laboratory procedures, and presents case reports. PMID- 11203558 TI - Effect of early exposure on the integration of dental implants in the baboon: Part 1--Clinical findings at uncovering. AB - There has been increased discussion on the advantages of a one- versus a two stage surgical approach in the placement of dental endosseous implants. This study evaluated the influence of early implant exposure on crestal bone height adjacent to the implant surface and Periotest values at uncovering in the baboon. Forty-eight implants (24 commercially pure titanium, 24 titanium alloy) were placed in maxillary and mandibular posterior sites in 6 baboons. Implant exposure was evaluated weekly for 3 weeks after implant placement. The level of bone adjacent to the dental implants was measured at placement from the top of the implant collar to the crest of the bone at the mesial, distal, buccal, and lingual surfaces. The maxillary sites were measured again at a 6-month uncovering, while the mandibular sites were measured at a 3-month uncovering. Periotest readings were also recorded at uncovering. Early implant exposure was more common in the mandible, with the majority occurring by the second week postplacement. There were no significant differences in the crestal bone height changes at uncovering between the pure titanium and alloy implants in either arch. In the maxilla, the changes in crestal bone height were not statistically different between exposed and nonexposed implants at any aspect. In the mandible, the difference in 3-month changes between exposed and nonexposed implants was significant for the distal, buccal, and lingual aspects. The overall percentage of implants with a Periotest reading in the "good" category was greater for the nonexposed sites as compared to exposed sites. The results of this study suggest that the two-stage surgical approach results in a better clinical outcome as compared to the one-stage approach in the baboon model. PMID- 11203559 TI - Placement of the preparation line and periodontal health--a prospective 2-year clinical study. AB - The aim of this prospective clinical 2-year study was to determine whether the placement of the proximal margins of crowns within the zone of the biologic width results in periodontal alterations. In 41 patients, 116 prepared teeth as well as 82 unrestored, healthy contralateral teeth were examined. The following indices were determined before as well as 3, 6, 12, and 24 months after preparation: hygiene index, papillary bleeding index (PBI), and probing depth. After preparation, the distance between the restoration margins and the alveolar crest was measured with a modified periodontal probe on both proximal aspects of each tooth. These values were classified into 3 groups: I = < or = 1 mm between crown margin and alveolar crest, II = 1 to 2 mm, and III = > 2 mm. In addition, radiographs were taken directly after cementation of each restoration and after 12 and 24 months. The hygiene index did not significantly vary during the investigation, but PBI increased in all groups. The highest PBI increase was found in group I; in this group, the most significant increase was found between 3 and 6 months after preparation. The mean probing depth only increased in group I during the first 3 months after preparation on the mesial aspects. Only minor changes were found on the distal aspects of the teeth in group I and on all aspects in groups II and III. No alterations of the bone levels were diagnosed on the radiographs. These results indicate that the location of the restoration margins within the zone of the biologic width may impair the periodontal health of restored teeth. PMID- 11203560 TI - Surgical template for completely edentulous patients. AB - Implant angulation is of utmost importance for fabrication of esthetic, hygienic, and functional prostheses, even in the treatment of completely edentulous patients. Most mandibular surgical templates are not reliable because of a lack of stability resulting either from severe resorption of the mandible or from the interference of mucoperiosteal flaps elevated during surgery. This article describes a technique for fabrication and surgical application of a stable template for the completely edentulous mandible. By combining the mandibular template with a maxillary duplicate denture, the problem of lack of stability can be overcome. A consistently reliable reference for implant placement in the edentulous mandible, specifically in relation to implant angulation (trajectory), can be obtained. PMID- 11203561 TI - Coronal ridge augmentation in the absence of bilateral bony plates around a pathologically denuded implant surface. AB - Guided bone regeneration via an osteopromotive barrier is indicated in different alveolar bone deficiencies and in periimplant bone destruction around pathologically denuded exposed implants. Regeneration of the osseous volume is determined by understanding the biologic behavior response of hard and soft tissues in guided tissue regeneration procedures. Consequently, a meticulous surgical approach is mandatory to preserve wound healing cascades and tissue stability. However, hard tissue augmentation in the nonsupported coronal direction has been unpredictable. A case report is presented in which a severely defected ridge around a pathologically exposed functional implant combined with a destructive extraction site was restored and regenerated. Bovine bone mineral particles (Bio-Oss) served as the graft material and were followed by an expanded polytetrafluoroethylene (e-PTFE) occlusive membrane as a bilateral regenerative tissue guide. Subsequently, 2 additional implants were placed in the augmented hard tissue ridge. PMID- 11203562 TI - Immediate transmucosal implant placement: a report of 2 cases. AB - Immediate placement of implants into fresh extraction sockets has the advantages of decreasing the recommended period of healing, reducing the resorption of the alveolar bone, and achieving optimal esthetic results. A high rate of success with immediately placed implants has been reported in the literature. Conventional intervention involves 2 or 3 surgical visits, and this may not be accepted by the patient or may be of some inconvenience. The technique described involves only one surgical visit at which a transmucosal endosseous root-form implant is inserted, followed by application of a resorbable membrane. PMID- 11203563 TI - Periodontal medicine in the next millennium. PMID- 11203564 TI - Histology of a human biopsy section following the placement of a subepithelial connective tissue graft. AB - This case report histologically examines the type of attachment that can occur after root coverage of a long-standing facial recession defect on a maxillary premolar with a subepithelial connective tissue graft. Histologic findings suggest that various types of tissue attachment, including periodontal regeneration, may occur over a recession defect after placement of a subepithelial connective tissue graft. In the present case, it was noteworthy that after 1 year the greatest area of exposed root surface was covered by a connective tissue attachment (adhesion), which had remained intact during orthodontic movement and distal drifting of the tooth. PMID- 11203565 TI - Treatment of Class II furcations with autogenous bone grafts and e-PTFE membranes. AB - This article reports a successful clinical regimen of treatment for the Class II furcation defect. Twenty-eight patients with molar teeth demonstrating Class II furcations were treated with regenerative therapy with the goal of regenerating lost interradicular periodontium. The treatment selected included scaling and root planing, surgical flap design that would enable the flap to completely cover the surgical site, complete enucleation of granulation tissue, tetracycline root conditioning, a particulate autogenous bone graft, and an expanded polytetrafluoroethylene (e-PTFE) membrane. Of the twenty-eight consecutive patients treated, twenty-five demonstrated no postoperative clinical evidence of furcation invasion, for a success rate of 89%. Eleven sites were reopened 8 to 9 months postsurgical and presented complete furcation fill with a hard, bone-like tissue. Three teeth were judged to be failures because clinical assessment revealed persistent furcation invasion. The absence of histologic evidence precludes the presumption that complete periodontal regeneration occurred. PMID- 11203566 TI - Sinus grafting with porous bone mineral (Bio-Oss) for implant placement: a 5-year study on 15 patients. AB - The efficacy of Bio-Oss as a graft material for sinus floor elevation was studied in 15 patients. A total of 20 sinus augmentation procedures was performed, and 6 months later 57 implants were placed into the augmented sinuses. New bone formation was confirmed in biopsies of 3 patients (new bone: 21.08% +/- 7.25% after 6 mo, 27.55% +/- 4.88% after 12 mo; Bio-Oss: 39.17% +/- 4.36% after 6 mo, 27.01% +/- 11.64% after 12 mo). After a mean loading period of 4.0 +/- 0.5 years (range 3.2 to 4.8 y), 56 implants remained in place. This study confirms Bio Oss's good osteoconductive properties. PMID- 11203567 TI - Retrospective analysis of Frialit-2 implants in the augmented sinus. AB - The aim of the present study was to investigate clinical and radiographic data of patients treated with implants in the posterior maxilla in combination with sinus augmentation. Study parameters included Periotest values, radiographic analysis, and survival/success rates up to 5 years. Clinical and radiographic criteria resulted in a success rate of 92.7% for sinus implants. Radiographically, the sinus implants showed a mean coronal bone loss of 0.5 mm at 6 months and 1.2 mm at 48 months. The results showed stable periimplant parameters for sinus implants during the observation period of 5 years. The success rates showed no significant differences regarding different implant-supported treatment options for the posterior maxillary region. PMID- 11203568 TI - Clinical and histologic evaluation of human gingival recession treated with a subepithelial connective tissue graft and enamel matrix derivative (Emdogain): a case report. AB - A mandibular canine with significant gingival recession was selected for a pilot study to measure the attachment modalities resulting from mucogingival surgery. The tooth had 6 mm of recession as measured from the cementoenamel junction to the gingival margin, minimal pocketing, and no keratinized gingiva. The treatment regimen consisted of a subepithelial connective tissue graft (SCTG) plus Emdogain applied to the root surface. The tooth was extracted en bloc 6 months after surgery and processed histologically in a buccolingual plane. The tooth demonstrated a 2-mm gain of attachment and a 3-mm gain in keratinized tissue. The histologic study evidenced the migration of the junctional epithelium 1.2 mm apical to the sulcus. New cementum, evidence of newly formed woven bone, and connective tissue fibers anchored in the new cementum were evident. PMID- 11203569 TI - Compressive shear strength of core materials and restoring techniques. AB - In this study, ninety extracted endodontically treated mandibular molars were mounted in acrylic resin blocks. Five groups of eighteen extracted teeth were prepared by two different techniques. A peripheral shelf 2 mm deep and 1.4 mm wide was prepared as a first technique, while TMS pins were used in the second group. The teeth were then restored with five different core materials: silver reinforced glass-ionomer, resin-modified glass-ionomer, self-cured glass-ionomer, polyacid-modified composite resin, and titanium-reinforced composite resin. An Instron testing machine was used to apply shear force at a crosshead speed of 2 mm/min until fracture occurred. The results were obtained statistically using analysis of variance and least significant difference tests. According to the results of this study, Ti-core and composite resin were the strongest core materials when subjected to shear forces, and the most retentive preparation design was the vertical-pin design. The fractures of these materials with a vertical-pin design were mostly seen at the core and the tooth. PMID- 11203570 TI - Improved closure rate of Class III furcations using a layered GTR technique. AB - In this study, 24 furcation defects in 12 patients were treated by either (1) a polylactide resorbable membrane (Guidor) plus a polyglactin mesh (Vicryl) and demineralized freeze-dried bone allograft (DFDBA), or (2) a polylactide resorbable membrane and DFDBA. All defects were reentered after 9 months. Class III furcations closed 66% of the time when treated by the first method, while the closure rate was only 33% when treated by the second method (no polyglactin mesh). Defects with a vertical opening of < or = 4 mm closed 74% of the time, while those with vertical openings > 4 mm closed only 11% of the time. PMID- 11203571 TI - The single-incision palatal harvest technique: a strategy for esthetics and patient comfort. AB - The use of connective tissue grafts for root coverage and ridge augmentation is a proven, effective treatment modality. Complications associated with the palatal donor site can arise because of incomplete primary closure of the palatal wound or sloughing of the overlying tissue. This article presents a new technique for the atraumatic harvesting of connective tissue grafts from palatal donor sites. The main advantage of this single-incision technique is the primary closure of the palatal flap, resulting in less pain and sensitivity and fewer postoperative complications. A review of the technique and its indications, rationale, and limitations is presented. PMID- 11203573 TI - The exciting world of interdisciplinary dentistry. PMID- 11203572 TI - Effect of unintentional exposure of 2-stage implants upon subsequent osseointegration: histologic findings 6 months postloading. AB - The purpose of this study was to evaluate the effect of early spontaneous exposure of 2-stage implants upon subsequent histologic bone contact following occlusal loading. As part of a study comparing 2 types of metallic threaded implants, 48 implants (24 CPTi and 24 Ti-13Nb-13Zr) were placed in maxillary and mandibular posterior sites in 6 baboons. Implant exposure was evaluated at time of placement and at each weekly visit for the first 3 weeks, then at 1, 2, and 3 months, and also at 6 months for the maxilla. Block sections were removed 6 months after the implant restoration was placed into function. One third (33%) of the maxillary implants became exposed, while 66.5% of the mandibular implants became exposed, mostly at 1 to 3 weeks. For all maxillary implants, fibrous tissue contact in the unintentionally exposed group (20.0%) was significantly greater than in the group that remained submerged (7.7%). Maxillary implants remaining submerged exhibited more sinus contact. For all mandibular implants, bone contact in the exposed group (38.9%) was significantly greater than in the submerged group (24.3%). Similarly, exposed implants exhibited less fibrous tissue contact. All other parameters in both maxillary and mandibular arches were statistically similar when comparing unintentionally exposed implants to those that remained submerged. This study suggests that accidental exposure of 2-stage implants should result in overall similarities in postloading bone contact to 2 stage implants that remain submerged during the early postoperative healing period. PMID- 11203574 TI - Changing periodontal paradigms: therapeutic implications. AB - Many paradigms concerning the epidemiology, pathogenesis, and systemic impact of periodontal diseases have been modified. For example, bacterial biofilms are essential to induce periodontitis, but their mere presence is not sufficient to initiate disease. It is also now recognized that the host response to these biofilms causes most of the destruction of the periodontal tissues. Codeterminants that influence the clinical severity of the disease process include environmental, genetic, and acquired factors. In general, the prevalence of advanced periodontitis and the incidence of disease progression are lower than previously believed. However, periodontitis remains the most common chronic illness. In addition, the finding that acquired systemic diseases may predispose individuals to periodontitis, and conversely that periodontitis may be a risk factor for certain systemic diseases, has expanded the scope of periodontics. These changed paradigms and their consequences with regard to selecting therapies are discussed in this review article. PMID- 11203575 TI - Piezoelectric surgery in implantology: a case report--a new piezoelectric ridge expansion technique. AB - The purpose of this preliminary article is to present a new surgical technique that, thanks to the use of modulated-frequency piezoelectric energy scalpels, permits the expansion of the ridge and the placement of implants in single-stage surgery in positions that were not previously possible with any other method. The technique involves the separation of the vestibular osseous flap from the palatal flap and the immediate positioning of the implant between the 2 cortical walls. The case report illustrates the ridge expansion and positioning of implants step by step in bone of quality 1 to 2 with only 2 to 3 mm of thickness that is maintained for its entire height. To obtain rapid healing, the expansion space that was created for the positioning of the implant was filled, following the concepts of tissue engineering, with bioactive glass synthetic bone graft material as an osteoconductive factor and autogenous platelet-rich plasma as an osteoinductive factor. The site was covered with a platelet-rich plasma membrane. A careful evaluation of the site when reopened after 3 months revealed that the ridge was mineralized and stabilized at a thickness of 5 mm and the implants were osseointegrated. PMID- 11203576 TI - A retrospective study of dental implants in diabetic patients. AB - The efficacious placement of dental implants in diabetic patients remains controversial. Definitive guidelines with objective criteria, including the type of diabetes, age of onset, and level of long-term control, have not been determined. In addition, few relevant literature citations assess the survival rate of implants in diabetic patients. Therefore, it is the purpose of this study to assess the success and survival rates of dental implants in diabetic patients. In this retrospective analysis, 215 implants placed in 40 patients at 2 clinical centers were evaluated. Chart reviews and interviews provided medical and implant data. From the analysis, 31 failures occurred, for an overall success rate of 85.6%. Of these failures, 24 occurred within the first year of functional loading. The mean time of functional load was 4.05 +/- 2.6 years. When the success rate was analyzed by implant location, success rates for the maxilla and mandible were 85.5% and 85.7%, respectively. For the anterior and posterior regions, success rates were 83.5% and 85.6%, respectively. The lifetable analysis revealed a cumulative success rate of 85.7% after 6.5 years of function. Based on the data, the survival rate of dental implants in controlled diabetic patients is lower than that documented for the general population, but there is still a reasonable success rate. The increase in failure rate occurs during the first year following prosthetic loading. PMID- 11203577 TI - Clinical and histologic evaluation of human intrabony defects treated with an enamel matrix protein derivative (Emdogain). AB - An enamel matrix protein derivative (Emdogain) has been recently shown to promote periodontal regeneration in experimentally created recession-type defects. However, only limited histologic data from human material are available concerning the healing of intrabony periodontal defects following treatment with Emdogain. The aim of the present study was therefore to present the clinical and histologic results following the application of Emdogain in intrabony defects. Two patients with marginal periodontitis and deep intrabony defects adjacent to teeth scheduled for extraction were treated with Emdogain. The postoperative healing phase was uneventful in both cases. At 6 months following treatment, newly formed cementum with inserting collagen fibers was found in both specimens. In one case, the new attachment formation was also accompanied by bone neoformation. The results of this human histologic study indicate that Emdogain possesses the potential to stimulate new connective tissue attachment formation in human intrabony defects. PMID- 11203578 TI - Hard tissue ridge augmentation using a resorbable membrane and a particulate graft without complete flap closure. AB - Twelve patients with isolated alveolar ridge defects bordered by teeth on each side were treated and followed for 12 months. The treatment involved use of a resorbable membrane and a particulate graft without complete flap closure. Measurements taken at 12 months showed a significant mean osseous gain of 3.27 +/ 3.73 mm in mid-defect ridge width and an increase in height of 1.90 +/- 2.50 mm. PMID- 11203579 TI - Long-term evaluation of osseointegrated implants in regenerated and nonregenerated bone. AB - This investigation evaluated the predictability of dental implants subjected to bone regeneration procedures at the time of insertion. Fifty-two test implants were inserted into sites with periimplant bone defects. A calcium carbonate allograft material with or without a fibrin-fibronectin sealing system was used to fill the defects. Sixty control implants were inserted into an adequate volume of nonaugmented bone. Each of the 29 study patients received at least one test implant and one control implant. At the second-stage surgery, fill of the bone defect was assessed as complete or incomplete. The cumulative success rate was 91.7% (mean follow-up 55 mo) for the test implants and 93.2% (mean follow-up 59 mo) for the control implants. Within the test group, implants with complete bone fill achieved 97.6% success versus 59.1% success for implants with incomplete bone fill. These preliminary results suggest that implants placed with simultaneous bone regeneration procedures achieve long-term predictability that is comparable to that of implants placed in an adequate volume of bone, provided that complete bone fill of the periimplant defect is achieved. Long-term studies with other augmentation materials are needed to fully validate these findings. PMID- 11203580 TI - Improved bone regeneration and root coverage using a resorbable membrane with physically assisted cell migration and DFDBA. AB - Twelve patients with 2 Miller Class I or II buccal recession defects measuring > or = 3.0 mm were treated using the principles of guided tissue regeneration and followed for 12 months. The effectiveness of a polylactide (Guidor) resorbable membrane (GA sites) was compared to a combination treatment of polylactide membrane plus polyglactin root-lining mesh (Vicryl) and demineralized freeze dried bone allograft (DFDBA) (GVB sites) designed to enhance cell migration and bone regeneration. There was 90% mean soft tissue root coverage for the GVB sites and 78% for the GA sites. The mean osseous dehiscence area coverage with hard tissue was 75% for GVB sites and 30% for GA sites. PMID- 11203581 TI - To conserve or implant: which choice of therapy? AB - The longevity of teeth depends directly on the state of the periodontal tissues. Many etiologic factors can lead to the loss of a tooth. Tooth loss is frequently associated with bone resorption. The diagnosis of a condition and knowledge of its etiology are essential to assess the prognosis of the remaining teeth and to formulate the correct treatment plan. Many parameters must be investigated to ascertain an accurate diagnosis. An understanding of the patient's needs and the length and likely success of treatment guides the decision of whether to preserve teeth or extract them and place implants. Advanced periodontitis poses a major therapeutic dilemma. Judicious, strategic extractions may permit the placement of long implants in ideal positions. PMID- 11203582 TI - Clinical performance of novel-design porcelain veneers for the recovery of coronal volume and length. AB - The present study evaluated the clinical performance of bonded porcelain veneers (PV) restoring substantial coronal volume and length in the anterior dentition. Forty-eight PVs were placed in 16 patients, with systematic coverage and reconstitution of the incisal edge, including well-defined anterior guidance. A standardized protocol comprising diagnostic steps that integrate additive waxups and acrylic mockups was used. PVs were fabricated using feldspathic and low fusing porcelains in a refractory die technique. Incisal overlaps featured freestanding porcelain spans ranging from 1.5 to 5.5 mm. After a mean clinical service of 4.5 years, 13 clinical parameters for each tooth and 4 parameters that applied to persons were recorded. Permutation tests evaluated the effects of margin location, incisal edge span of porcelain, overbite, opposing contact location, and restoration age on ceramic failure and clinical marginal adaptation and seal. At recall, 100% of the veneers were satisfactory with minor interventions. The effect of slight marginal defects and porcelain cracking was negligible. Biologic, periodontal, and esthetic parameters showed excellent results, which were supported by 100% patient-reported satisfaction. All patients felt comfortable with the newly defined anterior guidance. Aging was negligible, and there were no significant effects of margin location (P > 0.08), incisal edge span of the ceramic, or overbite (P > 0.22) on ceramic failure and marginal performance. Minor alterations of the palatal margin, however, tended to be more frequent compared to facial locations, and were found especially when the opposing tooth contact in centric occlusion was located on the palatal margin (P = 0.028). Bonded ceramic restorations represent a reliable, effective procedure to restore extensive coronal volume and length in the anterior dentition. PMID- 11203583 TI - Human histologic evaluation of bioactive ceramic in the treatment of periodontal osseous defects. AB - This study examined the healing of intrabony defects around 5 teeth treated with bioactive glass ceramic (PerioGlas). Healing was evaluated by clinical measurements, radiographic observation, and histologic analysis. The protocol included a presurgical phase of scaling and root planing therapy, with measurements obtained immediately prior to the surgical procedures and after 6 months of healing. Following therapy there was a mean of 2.7 mm of probing depth reduction, 2.2 mm of clinical attachment gain, and 0.5 mm of recession. The histologic analysis revealed healing by a long junctional epithelium with minimal new connective tissue attachment to the teeth, except in one case where the intrabony region demonstrated new cementum formation and new connective tissue attachment. Graft particles were found to be biocompatible, as evidenced by being embedded in a stroma of dense connective tissue with minimal inflammatory infiltrate. There was minimal new bone formation limited to the most apical borders of the defects. No signs of periodontal regeneration as defined by new cementum, periodontal ligament, and bone formation on a previously diseased root surface were observed. Although the clinical results are encouraging and radiographs evidenced radiopacities within the defects, histologic analysis revealed that as a periodontal grafting material, bioactive glass ceramic has only limited regenerative properties. PMID- 11203584 TI - Clinical and microbiologic study of periodontal surgery by means of apically positioned flaps with and without osseous recontouring. AB - In periodontitis lesions with interproximal craters, periodontal flap surgery with osseous recontouring allows more apical positioning of the soft periodontal tissue than flap surgery without osseous recontouring. The present study determined the clinical and microbiologic responses to periodontal surgery with and without osseous recontouring in adult periodontitis lesions with interproximal craters. In 7 osseous surgery patients, osteoplasty and ostectomy were performed from the lingual/palatal aspect to eliminate interproximal osseous defects and to partly mimic the original alveolar bony transition to neighboring teeth. In 7 nonosseous surgery patients, the surgical flap was adapted to the preexisting osseous level. Clinical monitoring included periodontal probing depth, Plaque Index, gingival bleeding index, and radiographic examination. Samples of the subgingival microbiota were examined. In sites treated with osseous surgery, mean pocket depth was 5.5 mm at baseline, 1.9 mm at 1 month, 2.0 mm at 3 months, and 2.1 mm at 6 months. In sites not receiving osseous recontouring surgery, the corresponding pocket depths were 5.9 mm, 3.1 mm, 3.8 mm, and 4.1 mm. At baseline in the osseous surgery group, Actinobacillus actinomycetemcomitans was recovered from one patient and Porphyromonas gingivalis from 5 patients; posttreatment, these microbiota were not detected in any patient. In the nonosseous surgery group, the presence of A actinomycetemcomitans increased posttreatment, and levels of P gingivalis remained essentially unchanged after therapy. This study suggests that in patients not receiving adjunctive antibiotic therapy, apically positioned flap surgery with osseous recontouring is more effective than apically positioned flap surgery without osseous recontouring in reducing periodontal pocket depth and levels of major periodontal pathogens. PMID- 11203585 TI - Simplifying management of the posterior maxilla using short, porous-surfaced dental implants and simultaneous indirect sinus elevation. AB - This article describes the use of short, porous-surfaced root-form dental implants and an indirect, simultaneous, osteotome-mediated sinus elevation procedure to restore the posterior maxilla when as little as 3 mm of bone remain below the sinus floor. Results with 16 patients who are part of an ongoing prospective clinical trial using the Endopore implant show 100% success (using established criteria) with a mean implant length of 6.9 mm and a mean functional time of 11.1 months. This treatment approach greatly simplifies the management of the posterior maxilla with minimal bone height below the sinus floor. PMID- 11203586 TI - The use of autologous growth factors in periodontal surgical therapy: platelet gel biotechnology--case reports. AB - The role of polypeptide growth factors in periodontal regeneration has been documented through animal and human studies. Human platelets contain platelet derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) in their alpha granules. PDGF has been shown to play a role in periodontal regeneration. It has been demonstrated that TGF-beta has a very potent effect on cells associated with bone. The case reports presented demonstrate a new biotechnology in which platelet gel is used in combination with demineralized freeze-dried bone allografts for the treatment of periodontal osseous defects. The treated teeth presented with severe bone loss and a guarded prognosis. Platelet gel biotechnology was used as a novel treatment modality. A significant reduction in probing depths was noted, and radiographically significant amounts of new bone were visible as early as 2 months postoperative. Results up to 2 years postoperative are presented. PMID- 11203587 TI - Clinical evaluation of a new resin composite crown system to eliminate postoperative sensitivity. AB - This study evaluated the long-term clinical performance of a new resin composite restorative system with a 4-META dentin-bonding agent to seal complete crown preparations prior to temporization and after permanent luting with a companion resin cement. Complete-coverage crown preparations were completed on 33 vital teeth and 5 nonvital teeth (control). The new restorative material demonstrated satisfactory clinical performance for the 3-year test period. The dentin-bonding agent and its companion resin cement successfully eliminated postoperative hypersensitivity in 100% of the prepared vital teeth over the 3-year term, suggesting excellent seal of dentinal tubules exposed by the complete-crown preparations. PMID- 11203589 TI - Histologic analysis of a fractured implant: a case report. AB - This study presents the histologic analysis of an implant retrieved 14 months after loading because of a fracture in the collar region. The implant (Biovent) was removed with part of the periimplant tissues, and the block was prepared using cutting and grinding equipment to obtain 3 sections approximately 30 microns thick. The examination evidenced a high degree of osseointegration, with a bone-to-implant contact of 74% +/- 13%. The lamellar bone was dense and in close relation with the hydroxyapatite coating of the implant. The connection between the 0.4-mm hydroxyapatite coating and the metal was always very tight. The thickness of the metal at the break point was assessed to be 1.6 mm. Besides the relative weakness of the metal at the neck of the implant, other possible causes of failure are discussed. PMID- 11203588 TI - Human histologic evaluation of a bone graft combined with GTR in the treatment of osseous dehiscence defects: a case report. AB - There are many possible goals and outcomes of periodontal surgical therapy, but the ultimate goal is regeneration. Since the definition of periodontal regeneration is histologic, it is difficult to document. The purpose of this study was to evaluate a technique that combined a bone graft and guided tissue regeneration (GTR) to see if regeneration occurred. Four teeth with dehiscence type osseous defects that were scheduled for extraction were treated with bone grafts and GTR. During the surgical procedure, a notch was placed into the root at the apical extent of the calculus. The teeth were extracted with conservative block sections 7 months after the treatment. They were processed, sectioned, stained, and evaluated histologically. The results revealed that regeneration did not occur in any of the teeth treated. In 2 of the teeth new connective tissue attachment was formed. In these 2 teeth cementum could be seen in the notch with connective tissue fibers inserting into the cementum. In one of the teeth the junctional epithelium extended apical to the notch, while in 3 cases the epithelium stopped at or coronal to the notch. In this case report, no regeneration could be documented, but new attachment could be seen in 2 of the 4 teeth treated. PMID- 11203590 TI - Perceptions of dentistry. PMID- 11203591 TI - Tissue engineering technology for gingival augmentation procedures: a case report. AB - Tissue engineering technology has been used in periodontal surgery. A patient who needed gingival augmentation prior to a single prosthetic restoration was treated by means of a tissue engineering technique. Results are presented in this case report. PMID- 11203592 TI - A clinical study of root surface conditioning with an EDTA gel. I. Nonsurgical periodontal treatment. AB - The present study was undertaken to investigate if subgingival administration of an EDTA gel has any adjunctive effect to subgingival and supragingival root debridement. The investigation was performed in one study center involving 6 clinical investigators and 91 patients. The patients were selected from 2 patient populations: 41 were included from a consecutive referral material on a voluntary basis, and 50 were included from a maintenance care material at the clinic. No significant differences were found between the EDTA-treated and control groups with respect to clinical attachment gain or probing pocket depth reduction. The referral patients showed a significant improvement of pocket depth and attachment gain compared to maintenance care patients at the clinic. In multiple regression analyses, it was found that patients with small attachment losses at baseline responded better to treatment than patients with severe periodontitis. Also, in multivariate analyses, referral patients responded better than maintenance patients when controlling for other predictors. PMID- 11203593 TI - A clinical study of root surface conditioning with an EDTA gel. II. Surgical periodontal treatment. AB - The objective of the present trial was to assess the effect of an EDTA gel applied during surgical periodontal therapy on probing depth reduction and periodontal attachment gain, allowing for the influence on healing of smoking as well as postsurgical oral hygiene. For comparison, citric acid treatment and control surgery only were included. The investigation was performed in one study center involving one clinical investigator and 68 patients. The patients were selected from a consecutive referral material on a voluntary basis. No statistically significant differences between treatment groups concerning attachment gain or pocket depth reduction could be seen after 3 and 6 months. A subgroup of the sample--21 patients who scored zero on the bleeding index at 3 and 6 months postsurgery and did not smoke--had a borderline significantly higher attachment gain in response to experimental treatment as well as a significant pocket depth reduction 6 months postsurgery when controlling for age, gender, Plaque Index at baseline, and treatment in multiple regression analyses. However, this was true not only for EDTA treatment but for citric acid and control treatment as well. PMID- 11203594 TI - Maxillary sinus floor elevation using a combination of DFDBA and bovine-derived porous hydroxyapatite: a preliminary histologic and histomorphometric report. AB - The objective of the study was to determine the osteoconductive potential of bovine-derived porous hydroxyapatite (HA) in combination with demineralized freeze-dried bone allograft (DFDBA) as an alternative to autogenous grafting in the maxillary sinus. The study involved 5 patients treated with 2-stage sinus elevation procedures using a combination of DFDBA and Osteograf/N 300 and 700. The healing time before implant placement ranged from 6 to 13 months. At the time of reentry, a bone core was harvested from each patient and processed for histologic and histomorphometric analysis. Woven and lamellar bone formation was evident in all specimens. Mean trabecular bone volume was 27.92%. The amount of newly formed bone was positively correlated with healing time. The range of new bone formation was 5.36% (6 mo) to 43.68% (12 mo). Residual HA graft particles were evident in all specimens, and the amount was inversely correlated with time. HA particles were often surrounded by an intense inflammatory infiltrate. DFDBA particles, largely present in the 6-month biopsy, were not recognizable in the 10 , 12-, and 13-month specimens, suggesting complete replacement. The combination of Osteograf/N and DFDBA appears to be osteoconductive and may be considered a valid alternative to autogenous bone grafts in sinus lift procedures. Histomorphometric and histologic evaluation may also be used to monitor the status of the future implant site. PMID- 11203595 TI - Use of Emdogain in the treatment of deep intrabony defects: 12-month clinical results. Histologic and radiographic evaluation. AB - The objective of this study was to evaluate the application of an enamel matrix derivative (Emdogain) in deep periodontal pocket therapy. Twenty-one patients presenting intrabony and interproximal defects that could be treated with guided tissue regeneration were selected. The intrabony defects were divided into deep (< 9 mm) and very deep (> or = 9 mm) defects. Bleeding on probing, Plaque Index, probing pocket depth, mobility index, gingival recession, probing attachment level, and surgical bone level were measured at baseline. At 12 months, cases were reexamined and indices recorded again. The mean probing depth decreased from 8.1 +/- 2.1 mm to 3.2 +/- 1.5 mm; attachment level decreased from 10.4 +/- 2.4 mm to 7.0 +/- 1.8 mm; recession increased from 2.3 +/- 1.4 mm to 3.8 +/- 1.8 mm; and surgical bone level decreased from 9.6 +/- 1.9 mm to 7.1 +/- 1.5 mm. No significant difference wa noted between bone defects with one or 2 walls, between local and generalized periodontitis, or between smokers and nonsmokers. Significant statistical difference was found, however, between deep intrabony defects and very deep defects when attachment gain was considered. No adverse reaction to the substance was noted. The good clinical results obtained were not confirmed by radiologic results; standardized and computerized radiographs at 12 months did not reveal significant improvement. The histologic examination carried out on 2 samples did not show evidence of new attachment. Further studies are necessary to clarify the action mechanism and to evaluate the long-term results of this method. PMID- 11203596 TI - The use of distraction osteogenesis to induce new suprabony periodontal attachment in the beagle dog. AB - Using a technique called distraction osteogenesis (DO), orthopedic surgeons are capable of reconstructing 4 to 5 cm of bone and soft tissue without bone grafts or pedicle flap procedures. DO has been used recently to generate maxillofacial bone as an alternative to maxillary and mandibular osteotomies. Using DO methodology, this study attempted to regenerate supraalveolar buccal periodontium on the mandibular second, third, and fourth premolars of beagle dogs. A small but statistically significantly greater amount of new cementum was generated in experimental teeth, with no difference found between experimental and control groups with respect to regenerating alveolar bone. Further studies using modifications of this technique are warranted to explore the potential of DO as an alternative to conventional regenerative approaches. PMID- 11203597 TI - Combined periodontal-prosthodontic treatment of early-onset periodontitis--an alternative to implant therapy. AB - A variety of treatment systems should be available for patients whose dentitions are seriously compromised so that they may select customized treatment modalities that satisfactorily restore occlusal function, consider systemic conditions, and lessen the surgical and financial burdens. These requirements become more demanding when clinicians are faced with advanced cases of rapidly progressive periodontitis. Therefore, it is critical to establish sophisticated multidisciplinary treatment modalities for the successful management of these compromised patients. Obviously, because of various limitations, implant therapy cannot be the only solution. This article reports on the successful long-term management of seriously compromised early-onset periodontitis by a combined periodontal-prosthetic treatment as an alternative to implant therapy. PMID- 11203598 TI - Treatment of a cracked tooth with a resin-ionomer restoration and a connective tissue graft: a case report. AB - Treatment of a cracked tooth can be difficult and unpredictable. Quite often, the most predictable treatment possible is simply extraction. This is a case report of the treatment of a cracked tooth with a resin-ionomer restoration and a connective tissue with partial-thickness double pedicle graft. The crack was detected during a routine root coverage procedure using this type of graft. A resin-ionomer was used to repair the crack. Then, the root coverage procedure was completed. Complete root coverage was obtained, including the portion of the root that was repaired. The results remained stable and the tooth treated remained asymptomatic. Clinically, the treatment was a success. PMID- 11203599 TI - The use of a bone block graft from the chin for alveolar ridge augmentation. AB - Periodontal disease and tooth loss often leave the patient with an alveolar ridge that is less than adequate for endosseous implant placement. Alveolar bone grafting offers a clinically successful treatment option to regain all or some of this lost bone. This article describes the use of a bone block from the chin for the augmentation of the alveolar ridge. It relates the clinical techniques to the healing process in an effort to better understand the events involved. PMID- 11203600 TI - Resin-bonded fixed partial dentures and splints in periodontally compromised patients: a 10-year follow-up. AB - In the present study, 139 periodontally compromised patients received a complete periodontal treatment; in 104 cases this was followed by orthodontic treatment. At the end of the entire therapy, a total of 150 Maryland restorations (69 resin bonded fixed partial dentures and 81 resin-bonded splints) was placed and then followed for a period of up to 10 years (mean 6.7 y). Thirteen fixed partial dentures and 16 splints failed during the observation period; the 10-year cumulative survival rate from lifetable analysis was 76.2% (70.6% for fixed partial dentures and 80.7% for splints). PMID- 11203601 TI - Alexithymia and negative emotional conditions. PMID- 11203602 TI - Abnormal intracellular localization of Bax, an apoptosis inducer, in human lung cancer cell lines. PMID- 11203603 TI - An examination of the stress distribution in a soft-lined acrylic resin mandibular complete denture by finite element analysis. AB - PURPOSE: The aim of this study was to calculate the effect of a soft liner on stress distribution within a mandibular complete denture. Although patients have welcomed soft-lined complete dentures, early fracture is one of the main reasons for failure. To minimize and prevent prosthesis fracture, the understanding of the stress distribution within a prosthesis is important. MATERIALS AND METHODS: A 3-dimensional finite element model of a mandibular complete denture for a severely reduced residual alveolar ridge was constructed. The stress was calculated with linear static finite element analysis. The stress distribution in the soft-lined acrylic resin mandibular complete denture was compared with that of a conventional acrylic resin denture. The resulting stresses were displayed in terms of von Mises equivalent stress and the major principal stresses according to 5 different loading conditions: vertical loads in premolar, molar, and incisor regions; and oblique loads in premolar and molar regions. RESULTS: Oblique loads produced higher levels of stress in the labial notch regions than vertical loads, where tension was the primary mode of stress. Significantly reduced levels of von Mises stress were calculated in soft-liner layers under all loading conditions. Acrylic resin denture base portions, however, exhibited higher levels of von Mises stress in soft-lined complete dentures. CONCLUSION: Three-dimensional finite element analysis gave a realistic explanation of denture fractures and patient response to mandibular complete dentures with and without soft linings. Control of excess lateral occlusal contact might be helpful to reduce the probability of a fracture in soft-lined mandibular complete dentures. PMID- 11203604 TI - Two-unit cantilevered resin-bonded fixed partial dentures--a retrospective, preliminary clinical investigation. AB - PURPOSE: The aim of this study was to retrospectively evaluate the clinical retention and abutment movement of 2-unit cantilevered resin-bonded fixed partial dentures (FPD) that were inserted at Prince Philip Dental Hospital in Hong Kong. MATERIALS AND METHODS: Of 45 patients who were identified from a hospital computer search after receiving a 2-unit cantilevered resin-bonded FPD, 31 were clinically examined (33 FPDs). For each patient the following data were recorded: gender, age, cementation date, endodontic treatment if performed, bone support, tooth mobility, and FPD tipping or drifting. Data about any debonds with subsequent treatment and patient satisfaction on a 10-point scale were also recorded. RESULTS: The mean service life for the 33 prostheses was 30 +/- 18 months, with a range of 72 days to 67 months. One prosthesis debonded, resulting in a clinical retention rate of 97%. No rotation, drifting, or tipping was observed for any of the prostheses during the short period of this study. CONCLUSION: Two-unit cantilevered resin-bonded FPDs are successful in the short term, but further research is required to determine if they offer a viable alternative to fixed-fixed resin-bonded FPD designs. PMID- 11203605 TI - Effect of accelerated aging on the color stability of cemented laminate veneers. AB - PURPOSE: The effect of the aging process on color stability of light-cure, dual cure, and self-cure resin cements used for luting laminate veneers was investigated in this study. MATERIALS AND METHODS: Dyract Cem (self cure), Twinlook (dual cure), and En Force (light cure) cements, 0.30 mm thick, were polymerized on laminate veneers that were 13 mm in diameter and 0.50 mm thick in an A2 shade. Five specimens were made for each material. The specimens were subjected to an accelerated aging process in a Weather-Ometer for 900 hours. Spectrophotometric analyses were made after 300, 600, and 900 hours of accelerated aging time. Overall color difference (delta E*ab) was determined using the CIE-LAB system for measuring small color differences. Chroma changes (delta C*ab) and hue differences (delta H*ab) were also determined. delta E*ab, delta C*ab, and delta H*ab were analyzed by one-way analysis of variance, t test for dependent samples, and Tukey honestly significant difference (HSD) tests. RESULTS: delta E*ab values determined for the materials in this study varied in the acceptable range of 1.9 to 2.7. Different aging times caused no significant differences in delta E*ab, delta C*ab, or delta H*ab values for any of the materials. There were no significant differences in the amount of overall color change among the 3 resin cements at the same aging period. Twinlook material showed the greatest chroma change at each aging time. The greatest hue change was determined for Dyract Cem material. CONCLUSION: The light-cure resin cement tested can be proposed as a suitable material for luting laminate veneers, but long-term clinical studies are necessary to verify these experimental findings. PMID- 11203606 TI - Prosthodontic decision making among general dentists in Sweden. III: The choice between fixed partial dentures and single implants. AB - PURPOSE: The purpose of this study was to describe how dentists evaluated the importance of various items related to a treatment choice between fixed partial dentures (FPD) and single implants, and to analyze if the differences could be explained by dentist-related variables such as social and demographic attributes, job situation, and attitudes. MATERIALS AND METHODS: Questionnaires were sent to a random sample of 2,059 Swedish general dentists, with a response rate of 76%. In the questionnaire, the choice between an FPD and a single-implant restoration in a clinical situation was presented. Fifteen items were constructed and the dentists were asked to mark on visual analogue scales the relative importance he or she gave the different items. The items were analyzed through principal components analysis, where a three-factor solution was obtained; the factors were labeled as "time," "health," and "comfort." The factors were run as dependent variables in multiple regression analyses. RESULTS: The items evaluated as most important were "prognosis for delivered treatment" and "patient's wish." Large individual differences were seen, but the differences between groups of dentists were small. Male dentists considered the "health" and the "comfort" factors to be more important compared to female dentists. The attitudinal variable "patient information" was significantly associated with the "time" factor and, inversely, with the "comfort" factor. CONCLUSION: Differences between individuals were great, but between groups of dentists the differences were only minor. Multivariately, the attitudinal variable "patient information" showed significant associations with the "time" and the "comfort" factors. Dentist-related variables explained little of the variations. The results further indicated a low personal knowledge concerning implant treatments. Psychologic methods might explain more of the individual differences in prosthodontic decision making, but these are not easily used in a questionnaire study. PMID- 11203607 TI - Angular asymmetries of the human face. AB - PURPOSE: The determination of an acceptable occlusal plane is essential for the development of esthetic prosthodontic restorations. However, since most faces are not symmetric, a method was developed for measuring facial angular asymmetry, i.e., the divergence from the vertical or horizontal of the line joining the midpoint of the intercanthal line and the philtrum of the lip, the interpupillary line, the intermeatal line, the lip commissure line, and the intercuspid line. MATERIALS AND METHODS: Standardized frontal images (mouth closed, smiling, and biting on a wooden spatula) of 100 subjects were taken using a digital camera. These images were downloaded into a computer, and the angles between the various facial lines and the horizontal were measured. The subjects were grouped by sex, age, and history of trauma and orthodontic treatment. RESULTS: No statistically significant differences were found between the mean values for each group. CONCLUSION: Asymmetry of the face can be measured using digital camera imaging and computer analysis. A range of facial asymmetries that can influence the choice of occlusal plane during prosthodontic treatment exists. Thus, the use of an occlusal plane parallel to the ala tragus and interpupillary lines, as often advocated by prosthodontists, may result in less than ideal esthetics in the final restoration. PMID- 11203609 TI - Welcome to the IJP in the year 2000. PMID- 11203608 TI - In vitro tensile bond strength of adhesive cements to new post materials. AB - PURPOSE: The purpose of this study was to measure the in vitro tensile bond strength of 3 types of adhesive resin cements to stainless steel, titanium, carbon fiber-reinforced resin, and zirconium oxide post materials. MATERIALS AND METHODS: Disks of post materials were polished to 600 grit, air abraded, and ultrasonically cleaned. Zirconium oxide bonding surfaces were pretreated with hydrofluoric acid and silanated. Bis-Core, C&B Metabond, and Panavia cements were bonded to the post specimens and placed in a humidor for 24 hours. Post specimens were debonded in tension. Means and standard deviations (n = 5) were analyzed by 2-way analysis of variance. Tukey-Kramer intervals at the 0.05 significance level were calculated. Failure modes were observed. RESULTS: Panavia 21 provided the highest bond strengths for all types of post materials, ranging from 22 MPa (zirconium oxide) to 37 MPa (titanium). C&B Metabond bonded significantly more strongly to stainless steel (27 MPa) and titanium (22 MPa) than to zirconium oxide (7 MPa). Bis-Core results were the lowest, ranging from 16 MPa (stainless steel) to 8 MPa (zirconium oxide). In most cases, bonds to carbon fiber post materials were weaker than to stainless steel and titanium, but stronger than to zirconium oxide. In general, higher bond strengths resulted in a higher percentage of cohesive failures within the cement. CONCLUSION: Panavia 21 provided the highest bond strengths to all post materials, followed by C&B Metabond. In most cases, adhesive resins had higher bond strengths to stainless steel, titanium, and carbon fiber than to zirconium oxide. PMID- 11203610 TI - Factors affecting the shear bond strength of bonded composite inlays. AB - PURPOSE: This article analyzes the influence of different pretreatments on the bond strength between inlays and the resin cement of three different composite inlay systems: Z-100, Targis, and Art Glass. MATERIALS AND METHODS: Four separate treatments of the composite-bonding agent interface were investigated: (1) untreated surface, (2) grinding, (3) sandblasting, and (4) sandblasting followed by silane treatment. Surface topography, roughness, and shear bond strength were evaluated using digital scanning electron microscopy, confocal laser scanning profilometry, and a Lloyd LRX equipped for shear bond testing, respectively. RESULTS: The bond strength is presented both with respect to composite surface pretreatment and with respect to different composite inlay systems. Independent of the composite inlay system, the sandblasted and silane-treated surface was found to give the highest bond strength values, followed by the sandblasted and ground surfaces. The untreated surface showed the lowest bond strength. For pretreated surfaces, Targis showed the highest (P < 0.05) bond strength values, followed by Art Glass and Z-100. This distribution, however, was reversed for the untreated interface, where Z-100 showed the highest bonding strength (P < 0.05). CONCLUSION: Surface pretreatment and roughness as well as the inlay material have an impact on the bond strength and the retention of composite inlays. PMID- 11203611 TI - Bond strength of denture teeth to denture base resins. AB - PURPOSE: The study examined the bond strength between 2 types of denture teeth and 3 denture base resins. The denture teeth were untreated, prepared with diatorics, or treated with dichloromethane, a solvent. MATERIALS AND METHODS: Conventional denture teeth and cross-linked denture teeth were bonded to either a heat-cured denture base resin, a microwave-cured denture base resin, or a pour type denture base resin. Compressive load was applied at 45 degrees on the palatal surface of each tooth until fracture. RESULTS: Conventional resin teeth possessed higher bond strength than cross-linked denture teeth. The heat-cured denture base resin significantly surpassed the microwave-cured denture base resin in bond strength. Both materials were better than the pour-type resin. The application of dichloromethane resulted in a significantly better improvement in bond strength compared to the use of diatorics. CONCLUSION: It is recommended that dichloromethane be applied on the denture teeth ridge-lap area prior to denture base processing. PMID- 11203612 TI - Surface roughness and flexural strength of self-glazed, polished, and reglazed In Ceram/Vitadur Alpha porcelain laminates. AB - PURPOSE: Because of existing controversy, the present study investigated 3 methods for reducing surface roughness and improving the strength of porcelain restorations. MATERIALS AND METHODS: Ninety laminated In-Ceram/Vitadur Alpha self glazed porcelain disks were fabricated and randomly divided into 3 groups (n = 30 each). Group 1 consisted of 30 of the original disks. The remaining 60 disks were then polished by 6 operators according to the recommendations of the American Academy of Esthetic Dentistry; group 2 consisted of 30 of these polished disks. The remaining 30 polished disks were reglazed (group 3). Average roughness values (Ra) of the veneers were measured by a profilometer. In each group, 20 disks were subjected to a flexure test, with 10 of the In-Ceram cores and 10 of the Vitadur Alpha veneers placed in tension. RESULTS: The Ra values were 0.5 +/- 0.1 micron, 0.7 +/- 0.3 micron, and 0.4 +/- 0.1 micron for groups 1 to 3, respectively. Following one-way analysis of variance (ANOVA), Bonferroni's multiple comparison tests found that groups 1 and 3 were significantly smoother than the polished group (P < 0.001). Reglazed disks were also significantly smoother than the original self-glazed disks (P < 0.01). With the veneers in tension, the flexural strengths were 151 +/- 22 MPa, 118 +/- 22 MPa, and 172 +/- 27 MPa for group 1 to 3, respectively. Following one-way ANOVA, Bonferroni's multiple comparison tests found that groups 1 and 3 were similar and were significantly stronger than the polished samples (P < 0.05 and P < 0.001). CONCLUSION: Reglazing polished porcelain surfaces significantly improved the surface texture and flexural strength of the materials tested. PMID- 11203614 TI - Future of prosthodontics, and of undergraduate and graduate training. PMID- 11203613 TI - The effect of placement and quantity of glass fibers on the fracture resistance of interim fixed partial dentures. AB - PURPOSE: Polymers used in interim fixed partial dentures (FPD) have recently been reinforced with fibers. The aim of this study was to determine the influence of the position of the fiber reinforcement on the fracture resistance of interim FPDs. In addition, the influence of quantity of fibers and the length of span of the FPD on the fracture resistance was investigated. MATERIALS AND METHODS: FPDs were fabricated from a resin mixture of polyethylmethacrylate powder and n butylmethacrylate liquid. Five FPDs from each group were made, and the FPDs were stored in water for 30 days before testing. The FPDs in the control group were unreinforced, and in the other groups the FPDs were reinforced either with two or three unidirectional continuous glass-fiber reinforcements and one woven glass fiber reinforcement. Different quantities of fibers were used and the fibers were placed in different locations in the FPD. The load was applied to the FPD by a steel ball placed in the cavity in the middle fossa of the pontic tooth. RESULTS: The load required to fracture the unreinforced FPDs varied from 372 to 1061 N. Mean fracture load of reinforced FPDs varied from 508 to 1297 N. One-way analysis of variance showed that the length of span and the quantity of fibers significantly affected the fracture load (P < 0.001, n = 5). By lengthening the span of the FPD, the reinforcing effect of glass fibers became more obvious. CONCLUSION: The results of this study suggest that the effectiveness of glass fiber reinforcement is most evident in interim FPDs with long spans and that the positioning of reinforcement considerably influences the strength of the FPD. PMID- 11203615 TI - Porcelain laminate veneers. A retrospective evaluation after 1 to 10 years of service: Part II--Clinical results. AB - PURPOSE: The objective of this study was to evaluate the clinical quality of 191 porcelain laminate veneers and to explore the gingival response in a long-term survey. MATERIALS AND METHODS: The clinical examination was made by two calibrated examiners following modified California Dental Association/Ryge criteria. In addition, margin index, papillary bleeding index, sulcus probing depth, and increase in gingival recession were recorded. Two age groups were formed to evaluate the influence of wearing time upon the clinical results. The results were statistically evaluated using the Kaplan-Meier survival estimation method, Chi-squared test, and Kruskal-Wallis test. RESULTS: A failure rate of 4% was found. Six of the total of seven failures were seen when veneers were partially bonded to dentin. Marginal integrity was acceptable in 99% and was rated as excellent in 63%. Superficial marginal discoloration was present in 17%. Slight marginal recession was detected in 31%, and bleeding on probing was found in 25%. CONCLUSION: Porcelain laminate veneers offer a predictable and successful treatment modality that preserves a maximum of sound tooth structure. An increased risk of failure is present only when veneers are partially bonded to dentin. The estimated survival probability over a period of 10 years is 91%. PMID- 11203616 TI - Etiology and diagnosis of tooth wear: a literature review and presentation of selected cases. AB - PURPOSE: This article presents an overview of etiologies associated with tooth wear. MATERIALS AND METHODS: Specific types of wear based on clinical findings and patient history are described. RESULTS: The occurrence and pattern of tooth wear are related to cultural, dietary, occupational, and geographic factors. Examples of tooth wear related to these factors with regional specificity are presented. CONCLUSION: The dental practitioner should recognize the characteristic signs of tooth wear, as they may be the first to discuss the problem with the patient. Management should be based on accurate diagnosis. PMID- 11203617 TI - A new application for craniofacial implants: wigs. AB - PURPOSE: The purpose of this study was to describe a new application of craniofacial implants, as anchoring elements for wigs. MATERIALS AND METHODS: In two patients, a split-skin graft was used to close a soft tissue defect in the occipital, parietal, temporal, and frontal region (defect size of 10 cm x 33 cm and 10 cm x 14 cm). Six titanium implants were placed in each patient. Six months after implant placement, abutment connection was performed and titanium magnets were adapted. Subsequently, an implant-retained wig was constructed. RESULTS: In a follow-up period of between 10 and 22 months no implant failed. The incorporated wigs effectively retain a functionally and cosmetically successful craniofacial rehabilitation. CONCLUSION: Despite these successful treatments, further research is needed before craniofacial implants as anchoring elements for wigs can be considered a standard option in the rehabilitation of craniofacial alopecic defects. PMID- 11203618 TI - Bonding durability of conventional resinous denture teeth and highly crosslinked denture teeth to a pour-type denture base resin. AB - PURPOSE: The study examined the bond strength between 2 types of resin denture teeth and a pour-type denture base resin after thermocycling. The denture teeth were untreated, prepared with diatorics, or treated with a solvent, dichloromethane. MATERIALS AND METHODS: Conventional denture teeth and crosslinked denture teeth were bonded to a pour-type denture base resin. Compressive load was applied at 45 degrees on the palatal surface of each tooth until fracture. The teeth were either thermocycled or not thermocycled. Porcelain teeth were also tested for comparison. RESULTS: There was no significant difference in bond strength between the conventional resin teeth and the crosslinked denture teeth. Thermocycling significantly decreased the bond strength of the 2 types of resin teeth but had no effect on porcelain teeth. The application of dichloromethane significantly improved the bond strength of the 2 types of resin teeth either before or after thermocycling. CONCLUSION: It is recommended that dichloromethane be applied on the denture teeth ridge-lap area prior to denture base processing. PMID- 11203619 TI - Interdental design of porcelain veneers in the presence of composite fillings: finite element analysis of composite shrinkage and thermal stresses. AB - PURPOSE: This study was conducted to optimize the interdental design (wraparound) of porcelain laminates bonded to teeth in the presence of preexisting composite fillings. MATERIALS AND METHODS: A finite element model (2-dimensional mesh generated from a horizontal cross section of a maxillary incisor) was used to evaluate the effects of luting composite shrinkage and thermal changes on the stress distribution within the ceramic. The mesh included 3 restorative designs (3 degrees of interdental wrapping) and a Class III composite filling. Curing contraction of the luting composite was simulated at baseline temperature (37 degrees C). Thermal loads from 37 to 60 degrees C and from 37 to 5 degrees C were assessed with and without preexisting composite shrinkage. Surface tangential stresses were calculated at the ceramic surface and interface. RESULTS: Curing contraction alone generated mostly compressive stresses (peaks at 15 MPa) at both the ceramic surface and interface. Stresses remained compressive (peaks at 20 MPa) when thermal changes were added, except for the conservative veneer with minimum wraparound, the margins of which showed potentially harmful tensile stress peaks (approximately 7 MPa). Deformation of the tooth-restoration complex tended to be more uniform for veneers with maximum wraparound. In the presence of thermal loads alone, opposite effects were observed on the restoration surface and the interface, with compressive stresses on one side (up to 13 MPa) and tensile stresses on the other (up to 9 MPa). This effect of proximal bending (explained by the nearby expansion/contraction of the composite filling) was attenuated by the significant reduction of the bulk of the preexisting interdental composite by the overlapping veneer. CONCLUSION: In the finite element environment, the negative effect of the nearby expanding/contracting composite fillings can be minimized by extending the veneer over the preexisting interdental restoration. Because of the precompressed state resulting from composite shrinkage, ceramics showed lower temperature-induced tensile stresses. PMID- 11203620 TI - Implant-supported mandibular overdentures retained with ball or bar attachments: a randomized prospective 5-year study. AB - PURPOSE: The aim of the present study was to evaluate the periimplant conditions and the maintenance requirements for implant-supported overdentures in the mandible retained with ball or bar attachments during a 5-year period. MATERIALS AND METHODS: Twenty-six completely edentulous patients had two Astra Tech dental implants placed in the anterior part of the mandible. The denture attachment system for the patients was chosen randomly by drawing lots. Eleven patients drew the bar attachment system and fifteen patients drew the ball attachment system. Plaque Index, Gingival Index, and probing pocket depth were assessed around each implant. Periotest values were recorded, and periodically identical intraoral radiographs were obtained with a specially designed film-holding device. RESULTS: No implants were lost from baseline to the 5-year registration. The periimplant conditions were very healthy after 5 years. No significant differences of the periimplant variables were recorded between the bar and the ball groups. During the first year of function, significantly more complications/repairs were registered in the bar group than in the ball group. In the following years, no significant differences were registered. The mean frequency of complications/repairs per patient per year was 1.0 in the bar group and 0.6 in the ball group during the 5-year observation period. CONCLUSION: Two implants with ball or bar attachment supported an overdenture in the mandible for 5 years with a 100% survival rate. No differences in marginal bone loss or health of the periimplant mucosa were observed between bar and ball attachment, but the frequency of technical complications/repairs per patient was higher around bar than ball attachments. PMID- 11203621 TI - Bond strength of luting cements to zirconium oxide ceramics. AB - PURPOSE: This study was conducted to determine the bond strength of some resin luting cements to zirconia ceramic. The hypothesis was that adhesive bonding capacity is influenced by different surface pretreatments designed for milled ceramic inlays. MATERIALS AND METHODS: Composite cylinders 5 mm x 5 mm were light cured on the ceramic surfaces for a shear test conducted in a test jig. Five surface treatments were studied: as received (from the milling machine), sandblasting with either 250- or 50-micron alumina sand, hydrofluoric acid treatment, and grinding with diamond burs. The tested luting cements were Panavia 21, Twinlook, and Superbond C&B. RESULTS: All debonding occurred at the interface between ceramic and composite cement. Superbond demonstrated the highest bond strength regardless of the surface treatments. Grinding the surface with diamond burs improved the bonding slightly for Twinlook and Panavia 21 and also showed the roughest texture. Washing with hydrofluoric acid had no significant influence on bond strength. CONCLUSION: Bond strengths for Twinlook and Pananvia 21 were quite low, and only Superbond showed a bond strength reasonably acceptable for clinical use; however, as no standard for bond strength has been established for inlay therapy, the other cements cannot be rejected as luting cements for inlays. PMID- 11203622 TI - Roughness of denture materials: a comparative study. AB - PURPOSE: Surface properties of denture materials are of clinical importance since they may affect plaque accumulation and staining. This in vitro study investigated the roughness of 20 commercially available denture materials. MATERIALS AND METHODS: Four denture base resins, nine hard lining materials, and seven soft denture lining materials were evaluated for roughness. Roughness measurements were made using a Mitutoyo Surftest SV-400, and the mean arithmetic roughness values (Ra) obtained were used for the comparisons. RESULTS: The overall Ra values ranged from 0.7 to 7.6 microns. The denture base materials group exhibited Ra values from 3.4 to 7.6 microns, whereas the hard liners were from 0.7 to 4.4 microns. The autopolymerized and visible light-cured soft liners presented Ra values from 0.7 to 3.5 microns, while the heat-cured soft liners ranged from 3.5 to 4.0 microns. CONCLUSION: The roughness exhibited by all of the materials tested (Ra values greater than 0.7 micron) indicates that there is a possibility for plaque accumulation, since 0.2 micron is considered the threshold below which no further bacterial adherence can be expected. PMID- 11203623 TI - Water sorption and flexural properties of a composite resin cement. AB - PURPOSE: The aim of this study was to assess the water sorption and determine the influence of water on flexural properties of a composite resin cement of 2 different viscosities. MATERIALS AND METHODS: A dual-cured composite resin cement of 2 different viscosities was tested according to International Standards Organization standards for dental composite materials. The samples tested for water sorption were stored in distilled water for 7 or 60 days. The samples tested for flexural properties were divided into 2 groups and stored either wet in distilled water or dry for 1, 7, or 60 days. After storage, a flexural test was performed with 3-point bending equipment. RESULTS: A significant increase in water sorption for both viscosities was registered as the storage time increased, but no significant difference between the 2 viscosities was recorded. Significantly lower strength and modulus were found for specimens that were wet stored for 60 days compared with the dry-stored ones, and significant changes in deflection at break were also registered. There were no differences in flexural properties between the 2 viscosities. Because of the lubricant and plasticizing effect of water on composite resin materials, the secant modulus and deflection at break seem to be valid methods to describe the complete deflection behavior. CONCLUSION: Water has an important effect on the flexural properties of composite resin cement after 60 days of storage time. No significant differences in water sorption and flexural properties were found between the high and low viscosities of the composite resin cement studied. PMID- 11203624 TI - Denture-induced fibrous inflammatory hyperplasia: a retrospective study in a school of dentistry. AB - PURPOSE: The aim of this study was to investigate the denture-induced fibrous inflammatory hyperplasia (FIH) that occurs around the borders of an ill-fitting denture, in relation to frequency of the lesion, age and sex distribution, length of denture use, and frequency of dysplasia. MATERIALS AND METHODS: A comprehensive review of FIH diagnosed in patients wearing dentures by the oral pathology diagnostic service at the University of Sao Paulo over 26 years (1971 to 1996) was undertaken, based on retrospective analysis of the oral histopathologic files. RESULTS: The frequency of FIH was 15% of the total number of pathologies diagnosed at the service of oral pathology in that period. The disorder occurred predominantly in the fifth and sixth decades of life and more often among females, at a proportion of 5:1. The frequency of FIH was higher for a length of denture use of between 1 and 10 years. Dysplasia was found in 4% of cases. CONCLUSION: The knowledge of some aspects of FIH, especially the possible histologic alteration of dysplasia, supports the importance of the diagnosis and treatment of the lesion and suggests that any excised tissue should be submitted to histopathologic evaluation. Education and regular review of patients who have worn dentures are essential if the development of FIH is to be prevented. PMID- 11203625 TI - Materials for interocclusal records and their ability to reproduce a 3 dimensional jaw relationship. AB - PURPOSE: The purpose of this study was to determine if accuracy and dimensional stability of vinyl polysiloxanes and irreversible hydrocolloids stabilized by a tray used for fixed prosthodontics, removable partial, and complete denture cases are comparable to those of waxes and record rims and if storage time (24 hours or 6 days) affects dimensional stability of the tested materials. MATERIALS AND METHODS: Two waxes, two record rims, three vinyl polysiloxanes, and one irreversible hydrocolloid (alginate) were examined. Three pairs of master casts with measuring steel rods were mounted on an articulator (initial position). Five records were made of each material, and the upper cast was remounted after 24 hours or 6 days so that deviations from the initial position could be measured. RESULTS: Vinyl polysiloxanes reinforced by a stabilization tray were the most accurate materials able to reproduce a settled interocclusal position. Mounting casts (fixed prosthodontics cases) without records gave accuracy similar to wax records. Record rims used for removable partial and complete denture cases produced lesser accuracy than vinyl polysiloxanes and irreversible hydrocolloid stabilized by a tray. Accuracy was not significantly affected by storage time. CONCLUSION: The results show that accuracy of vinyl polysiloxanes and irreversible hydrocolloids reinforced by a tray is superior to that of record rims with regard to the complete denture case and is among the most accurate with regard to the removable partial denture case. For fixed prosthodontics, however, reinforcement is unnecessary. PMID- 11203627 TI - A simplified technique for construction of an interim obturator for a bilateral total maxillectomy defect. AB - PURPOSE: This report describes a simplified method for construction of an interim obturator for a huge maxillary defect. MATERIALS AND METHODS: A medical grade silicone obturator was fabricated indirectly on a duplicate cast of the surgical defect for a patient with a bilateral total maxillectomy. This silicone obturator was attached to an acrylic plate by means of mushroom-like extension tags projecting from the fitting surface of the acrylic palatal plate. RESULTS: The obturator was well retained in the patient's mouth and markedly improved his ability to speak and swallow. CONCLUSION: This technique proved to be a simple, quick, and cost-effective method for construction of obturators for huge maxillary defects. PMID- 11203626 TI - A study of the bond strength and color of ultralow-fusing porcelain. AB - PURPOSE: The purpose of this study was to investigate the effects of different bonding agents, surface roughness, and acid pickling on the bond strength and color of ultralow-fusing porcelain fused to gold alloy. MATERIALS AND METHODS: Porcelain-metal specimens were made to 25 mm x 3 mm x 0.5 mm with a 1-mm porcelain thickness. A 3-point bending test was used to evaluate the bond strength. The color of the porcelain was measured using a dental chromameter, and the data were processed in the CIE Lab system. The color difference (delta E*) was calculated for the tested groups. RESULTS: Good bond strength and color could be achieved regardless of the use and type of bonding agent. Surface roughness and acid pickling had more effect on the bond strength than on color. CONCLUSION: The type of the bonding agent, surface roughness, and acid pickling influenced the bond strength but had minimal effects on the color of ultralow-fusing porcelain. This ultralow-fusing porcelain could produce a color closer to the Vita shade than the conventional low-fusing porcelain. PMID- 11203628 TI - Looking to the past and making choices for the future of dental education. PMID- 11203629 TI - International dental and prosthodontic research. PMID- 11203630 TI - In vitro fitting accuracy of copy-milled alumina cores and all-ceramic crowns. AB - PURPOSE: The purpose of this study was to evaluate the marginal and internal fit of alumina cores and all-ceramic crowns in a new preparation design for abutment teeth devised for copy milling. MATERIALS AND METHODS: Using conventional dies and dies from the new type of preparation design, 20 alumina cores were produced by copy milling, 10 cores in each die type. Also using the new type of die, another 10 final crowns were fabricated. Each of the 30 specimens was returned to its original die and embedded in epoxy resin. Each specimen was then sectioned labiolingually and measured for gaps at the margin, in the central area, and at the incisal edge. RESULTS: The alumina cores fabricated using the new type of die had mean gaps of 30 to 40 microns at the margins of the labial and lingual sides, which was significantly smaller than the gaps (67 to 130 microns) found in the alumina cores produced with the conventional type of die. The final crowns had mean gaps of 44 to 63 microns at the margins and on the inner surfaces. There was no significant difference in the gaps between the alumina cores produced using the new type of die and those found in the final crowns. CONCLUSION: The new type of die was effective in allowing the fabrication of all-ceramic crowns that provide excellent marginal and internal fit by copy milling. PMID- 11203632 TI - Evaluation of occlusal contacts in the dental laboratory: influence of strip thickness and operator experience. AB - PURPOSE: The purpose of this study was to evaluate the influence of recording strip thickness and of operator-dependent factors on the assessment of contact area on a cast mounted on an articulator. MATERIALS AND METHODS: Thirteen dental students and 13 experts (dentists and dental technicians) performed occlusal maneuvers on casts mounted on an articulator, using recording strips of 8- and 40 micron thickness. Contact area, force, and time of biting relative to each group of operators using each type of paper were compared. RESULTS: Both groups obtained significantly greater contact areas with the thicker strip. Students applied significantly stronger but shorter bitings than experts, but obtained smaller contact areas, particularly with the thinner strip. In operators, the extension of contact markings using the 8-micron strip was closely related to the biting time but not to the occlusion force, while neither time nor force of biting had a significant influence when using the 40-micron strip. CONCLUSION: The assessment of occlusal contact in the dental laboratory was significantly influenced by paper thickness, operator experience, biting force, and time. The 40-micron strip was less influenced by operator experience, strength, and duration of biting. PMID- 11203631 TI - A randomized 5-year clinical evaluation of 3 ceramic inlay systems. AB - PURPOSE: The present follow-up study aimed to evaluate the clinical quality and longevity of 3 ceramic inlay systems and compare them with gold inlays. MATERIALS AND METHODS: Twenty patients were treated with one Cerec, one Mirage, one Empress, and one gold inlay, respectively, inserted in a randomly selected order in the mandible. The inlays were examined independently by 2 calibrated examiners immediately after and 1, 3, and 5 years after luting. The inlays were rated using the California Dental Association (CDA) quality evaluation system. RESULTS: Two Empress inlays required replacement because of fracture between examination (Ex) 1 and Ex 2, and 2 Empress inlays were fractured between Ex 3 and Ex 4. One Cerec inlay had to be recemented after 3 months, and one Cerec inlay fractured between Ex 3 and Ex 4 and was replaced with a gold inlay. Examination showed that the mismatch of color increased from 15% to 50% between Ex 1 and Ex 4 for all ceramic systems. Visible evidence of ditching along the margin increased from 5% at Ex 1 to 70% at Ex 4, and an apparent discoloration of the margin between the tooth and the restoration was seen in 0% to 5% at Ex 1 compared to 30% to 55% at Ex 4. CONCLUSION: Eight percent of the ceramic inlays were fractured during the follow up period of 5 years. Based on the criteria of the CDA quality evaluation system, 92% of the 60 ceramic inlays and 100% of the 20 gold inlays were rated satisfactory 5 years after luting. PMID- 11203633 TI - Strength of relined denture base polymers subjected to long-term water immersion. AB - PURPOSE: This study was undertaken to characterize the long-term equilibrium flexural strength at proportional limit (FSp) of 4 denture reline polymers processed onto 4 denture base polymers. MATERIALS AND METHODS: A 3-point flexural test was applied on rectangular specimens of each denture base polymer-denture reline polymer. Each specimen was immersed in water for 4 months prior to and 4 months after reline. RESULTS: Significant differences existed among the relined specimens because of the denture base polymer variable, the denture reline polymer variable, and their interaction (P < 0.05). The descending order in FSp according to the denture base polymer, arranged in terms of statistical significance was: Acron approximately Acron MC > Triad > Palapress Vario, where approximately denotes no significant difference between Acron and Acron MC. The descending order in FSp according to the denture reline polymer, arranged in terms of statistical significance was: Triad > Rebaron > Rebaron LC > Tokuso Rebase. Significant difference existed among all of the denture reline polymers. CONCLUSION: The present study showed that the long-term equilibrium strengths of 4 denture reline polymers processed onto 4 denture base polymers were different. The strength of the relined specimen of a denture base is dependent on the strength of the denture base polymer and that of the reline polymer. PMID- 11203635 TI - Detail reproduction, contact angles, and die hardness of elastomeric impression and gypsum die material combinations. AB - PURPOSE: This study compared surface detail parameters, interfacial contact angles, and die hardness for some combinations of elastomeric impression and die materials. MATERIALS AND METHODS: Representative polyvinyl siloxanes, polyether, polysulfide, and reversible hydrocolloid impression materials and Type IV, Type V, and resin reinforced-Type IV die materials were evaluated using a factorial design. For the evaluation of surface detail reproduction, the width of the thinnest continuous line observed and the visually observed shape of the thick line were determined from samples formed using a master die conforming to American Dental Association specification 19. The contact angle of freshly mixed die material on the set impression was measured using a contact angle goniometer. Finally, hardness of the die material was determined. After conversion of the data to ranks if necessary, 2-way analysis of variance with Ryan-Einot-Gabriel Welsch (REGWQ) multiple comparison tests where appropriate were used to determine statistical significance. RESULTS: The thinnest continuous line demonstrated statistically significant impression material effects, and the observed shape of the thick line showed both statistically significant impression material and die material effects. For both contact angle and die hardness, a statistically significant interaction between the impression and die materials was found. CONCLUSION: Although statistically significant differences in each property were found, no specific combination of impression and die materials was identified as superior to another for all surface properties studied. PMID- 11203634 TI - The effect of polishing on surface roughness of tissue conditioners. AB - PURPOSE: Surface roughness can affect microbial colonization of long-term denture liners, alloys, and denture acrylic. The purpose of the present study was to examine the effect of finishing and polishing procedures on surface roughness of 4 temporary resilient denture liners (tissue conditioners). MATERIALS AND METHODS: Mean surface roughness was measured for 4 materials (Lynal, Visco-gel, Coe-Soft, and Functional Impression Tissue Toner [FITT]) finished in 4 ways: unfinished (control); polished; reduced, unpolished; and reduced, polished. Samples were allowed to polymerize at 37 degrees C for 24 hours, and the surface roughness was measured using a Mitutoyo Surftest 212. RESULTS: Mean surface roughness ranged from 1.8 +/- 0.8 microns for polished Lynal to 7.8 +/- 1.1 microns for reduced, unpolished FITT. All polished samples were smoother than unpolished samples (including controls), whether or not the samples were reduced with a bur. CONCLUSION: Polished samples of tissue conditioning material had lower mean surface roughness measurements than control or reduced, unpolished samples at the 95% level of confidence. There was no difference in mean surface roughness measurements of control samples and unpolished samples reduced with a bur at the 95% level of confidence. Mean surface roughness differed significantly between the materials tested. PMID- 11203637 TI - Changes in the masticatory function of complete denture wearers after relining the mandibular denture with a soft denture liner. AB - PURPOSE: The purpose of this study was to examine changes in the masticatory function of complete denture wearers after relining the mandibular denture with a soft liner. MATERIALS AND METHODS: Conventional complete dentures were fabricated for 6 completely edentulous patients. One month after completing adjustments of the dentures, maximum biting force, masticatory performance, and electromyography of the masseter muscle during mastication were recorded. Chewing strokes, chewing time, muscular activity, and masticatory rhythm were calculated using the recorded electromyography. The mandibular dentures were then relined with a soft liner. One month after finishing adjustments of the relined dentures, the same tests were performed. These values were compared using a paired t test (alpha = 0.05). RESULTS: When using the soft liner, masticatory performance and maximum biting force were significantly greater (P = 0.019 and P = 0.023, respectively). In addition, the number of chewing strokes was significantly lower (P = 0.020), and chewing time was reduced (P = 0.010). A more stable masticatory rhythm was also found in the initial chewing stage. The muscular activity tended to decrease after the insertion of the lined denture, but no significant difference was found between before and after relining. CONCLUSION: It was shown that applying a soft lining material to the mandibular dentures of 6 edentulous patients improved masticatory function with no adverse effect on the muscular task. PMID- 11203636 TI - Bonding to densely sintered alumina surfaces: effect of sandblasting and silica coating on shear bond strength of luting cements. AB - PURPOSE: An important determinant of the clinical success of ceramic restorations is the bond strength of the luting agent to the seating surface and the prepared tooth structures. Manufacturers of ceramic systems frequently specify both the luting agent and preluting treatment of the seating surface of the crown. Procera AllCeram is an all-ceramic crown comprising a porcelain-veneered coping of densely sintered, high-purity aluminum oxide. This study evaluated the shear bond strength of 4 luting agents: zinc-phosphate, glass-ionomer, resin-modified glass ionomer, and resin cement (dual cured) to Procera aluminum oxide coping material. The luting agents were subjected to different surface treatments: untreated, sandblasted, or silica coated by the Rocatec system. MATERIALS AND METHODS: Cylindric and cubic specimens of the coping material were luted together, and the shear force necessary to separate the cylinder from the cube was measured with a universal testing machine. The surfaces of the specimens were also analyzed. RESULTS: No significant differences were recorded for the shear bond strengths of the luting agents to the untreated aluminum oxide. Glass-ionomer and the resin modified glass-ionomer cements had the highest values (4.2 +/- 2.5 MPa and 4.3 +/ 1.9 MPa, respectively), and the lowest were 3.3 +/- 2.3 MPa for the resin cement and 3.2 +/- 1.0 MPa for the zinc-phosphate cement. Similar results were recorded for the sandblasted aluminum oxide surfaces, except with the glass-ionomer, which was significantly higher (12.9 +/- 2.4 MPa). For all 4 luting agents, the highest shear bond strength values were recorded for the silica-coated specimens; the highest was for the resin cement, at 36.2 +/- 7.8 MPa. CONCLUSION: The bond strengths between resin cement and aluminum oxide specimens treated by the Rocatec system were significantly higher than those of the other materials and surface treatments evaluated. PMID- 11203638 TI - Effects of electrobrightening on the fit surface of cobalt-chromium RPD frameworks. AB - PURPOSE: The purpose of this study was to compare 3 different electrobrightening techniques and 3 electrolytic solutions in their effects upon the fit surface of cast cobalt-chromium frameworks. MATERIALS AND METHODS: Fifty cast cobalt chromium frameworks, which were subsequently divided into batches of 10, were prepared according to a standard protocol. Three electrobrightening techniques were tested initially using a single brand of electrolyte (Croform) and a batch of 10 frameworks per technique. The loss of metal by weight was determined from the fit surface of each casting. The least corrosive technique of these 3 was used again with 2 other brands of electrolyte (Nobilium and E501) in a repetition of the protocol. The fit surfaces of 8 random samples cut from each batch of electrobrightened castings were viewed by scanning electron microscope (SEM). RESULTS: Statistical analysis applying a one-way analysis of variance and Bonferroni's multiple comparison of means test demonstrated that one immersion of the framework for 10 minutes at 1 amp when used in conjunction with Nobilium electrolyte removed the least metal (P = 0.001). The SEM study suggested that the Nobilium electrolyte also produced the smoothest surface. CONCLUSION: Electrobrightening techniques affect the amount of metal removed, and the electrolytic solution used influences the resultant surface. PMID- 11203639 TI - The prosthodontic maintenance requirements of mandibular mucosa- and implant supported overdentures: a review of the literature. AB - PURPOSE: This article presents a critical review of the literature on the prosthodontic maintenance requirements of mandibular mucosa- and implant supported overdentures. MATERIALS AND METHODS: A search of the literature produced 35 papers pertaining to prospective and retrospective studies. The relationship of these prosthodontic maintenance requirements to the axis of rotation treatment concept was examined. RESULTS: More often than not, 2 anterior mandibular implants either splinted (round or ovoid bars) or unsplinted (balls or magnets) have been used to evaluate this prosthodontic follow-up. Wide variation existed in the categories used for prosthodontic complications. Although principally related to alterations of overdenture contour and aspects of patrix and matrix maintenance, they also provide subjective information on relines and the rationale for avoiding overdenture fractures. These prosthodontic maintenance requirements undoubtedly have a direct impact on the time to retreatment of mandibular mucosa- and implant-supported overdentures. CONCLUSION: There appears to be a need for a more uniform, standardized categorization with criteria for determining prosthodontic success, in terms of maintenance requirements and complications, for mandibular mucosa- and implant-supported overdentures. Controlled prospective evaluations of exact prosthodontic maintenance requirements of mandibular overdentures using different systems are lacking and encouraged. There is also an absence of prospective studies on such maintenance requirements of mandibular overdentures using multiple round bars on 3 or 4 implants. PMID- 11203640 TI - Mandibular implant-supported overdentures: a prospective evaluation of the burden of prosthodontic maintenance with 3 different attachment systems. AB - PURPOSE: A prospective study on mandibular implant-supported overdentures using more than 2 Branemark implants splinted with multiple round bars evaluated a hypothesis that unnecessary prosthodontic maintenance would result from the contravention of accepted biomechanical principles. MATERIALS AND METHODS: A randomized prospective trial on 59 edentulous patients details prosthodontic maintenance and complications of 52 mandibular overdentures (11 unsplinted, 41 splinted) over a 3-year period. RESULTS: Prosthodontic maintenance was greater in the first year than in subsequent years, regardless of design. Comparison between the splinted designs with round bars revealed no statistically significant difference with either retentive clip activation or fractures. More than 70% of the retention clips in the 2-implant (single round bar) design needed activation, as compared to 44% of those with the 3-implant (double round bar) or 4-implant (triple round bar) design. Retention clip fracture occurred in 30% of patients with 3 or 4 implants and 16% of those with 2 implants. Relining the overdentures, regardless of design, revealed an excessive maintenance burden in 40% of overdentures. Remaking of overdentures was necessary in 21% of patients. CONCLUSION: Multiple round bars splinting 3 or 4 implants can still be a treatment concept in mandibular overdenture treatment. Results from prospective evaluation of this design indicate less prosthodontic maintenance of clip activation but more clip fractures than with 2 implants splinted with single round bars, although not at statistically significant levels. PMID- 11203641 TI - Research directions in implant prosthodontics. PMID- 11203642 TI - One-piece castings in fixed prosthodontics: a study of marginal adaptation using computerized SEM images. PMID- 11203643 TI - A comparison of laser-welded titanium and conventional cast frameworks supported by implants in the partially edentulous jaw: a 3-year prospective multicenter study. AB - PURPOSE: The purpose of this prospective multicenter study was to evaluate and compare the clinical performance of laser-welded titanium fixed partial implant supported prostheses with conventional cast frameworks. MATERIALS AND METHODS: Forty-two partially edentulous patients were provided with Branemark system implants and arranged into 2 groups. Group A was provided with a conventional cast framework with porcelain veneers in one side of the jaw and a laser-welded titanium framework with low-fusing porcelain on the other side. The patients in group B had an old implant prosthesis replaced by a titanium framework prosthesis. The patients were followed for 3 years after prosthesis placement. Clinical and radiographic data were collected and analyzed. RESULTS: Only one implant was lost, and all prostheses were still in function after 3 years. The 2 framework designs showed similar clinical performance with few clinical complications. Only one abutment screw (1%) and 9 porcelain tooth units (5%) fractured. Four prostheses experienced loose gold screws (6%). In group A, marginal bone loss was similar for both designs of prostheses, with a mean of 1.0 mm and 0.3 mm in the maxilla and mandible, respectively. No bone loss was observed on average in group B. No significant relationship (P > 0.05) was observed between marginal bone loss and placement of prosthesis margin or prosthesis design. CONCLUSION: The use of laser-welded titanium frameworks seems to present similar clinical performance to conventional cast frameworks in partial implant situations after 3 years. PMID- 11203644 TI - Observations of interproximal contact relations during clenching. AB - PURPOSE: Previous studies have shown that molar teeth pulsate at rest and displace linguoapically during clenching at maximal intercuspation. The aim of this study was to investigate interproximal contact during clenching by means of a charge coupled device (CCD) microscope. MATERIALS AND METHODS: Two male subjects aged 28 years with normal dentition and occlusions were selected for in vivo research. Optimum contact tightness was observed at contact points that were defined by some resistance to the insertion of a 50-micron-thick stainless steel strip; however, a 110-micron strip could not be inserted there [corrected]. Spaces between the teeth were detected using a CCD microscope on the buccal side by light bands emitted from the lingual side. During static observation, the chosen distance between the microscope and light guide was maintained using a special device. For dynamic observation, a palatal and lingual plate with a light source was fitted to each subject. Subjects were directed to clench with habitual occlusal force. To compare with in vivo observations, the relation between the width of the light band and the interproximal distance was estimated in vitro using 2 extracted teeth. Light bands were analyzed using software. RESULTS: In the 2 subjects studied, there was a 3- to 21-micron distance between adjacent teeth at rest, which disappeared during clenching. CONCLUSION: The results of the study sample examined indicate that teeth do not make contact with adjacent teeth at rest, but do so during clenching. PMID- 11203647 TI - Cytotoxic effect of methyl methacrylate on 4 cultured fibroblasts. AB - PURPOSE: The objective of this study was to examine the cytotoxic effect of methyl methacrylate (MMA) monomer on 4 mammalian fibroblasts. MATERIALS AND METHODS: Four cells--C3H10T1/2, L929, Balb/3T3 clone A31, and MC3T3-E1--were incubated for 6 days in 24-well microplates filled with 1 mL of Dulbecco's Modified Eagle medium containing MMA monomer that ranged from 0 to 200 mM/L. Cytotoxicity was evaluated by direct cell number count. RESULTS: L929 possessed the largest TC50 value (the amount of MMA that caused 50% cell death) (34 mM/L), and Balb/3T3 clone A31 had the least value (1 mM/L); C3H10T1/2 and MC3T3-E1 had intermediate values (25 mM/L and 16 mM/L, respectively). CONCLUSION: This study showed that the MMA monomer had dose-dependent cytotoxicity, which varied among the cells tested. PMID- 11203646 TI - Predicted incidence of excursive occlusal errors in common modes of articulator adjustment. AB - PURPOSE: Functional relationships between occlusal errors and articulator settings have been the subject of numerous investigations. It is, however, not known how frequently errors of a certain size occur under practical conditions. This study attempted to estimate the frequency of occlusal errors that can be expected with the different levels of registration and articulator adjustment that are currently used. MATERIALS AND METHODS: In 57 asymptomatic subjects, individual articulation parameters, including the condylar and Bennett angles, the spatial relation of dental arches, and the intercondylar distance, were determined experimentally. Tooth-guided lateral movements of the subjects' casts were simulated in a virtual articulator that was programmed to the individual parameters of each person. With respect to this reference setting, occlusal errors that would emerge with different modes of semi-individual adjustment were calculated. The intercondylar distance thereby remained fixed at 110 mm. RESULTS: With complete mean value setting, occlusal errors would exceed 200 microns at the second molar in 16% of the subjects and 300 microns in 6% of the subjects. Individual facebow registration of condylar angles and spatial relations would reduce these rates to 13% (200 microns) and 3% (300 microns). With additional setting of Bennett angles, occlusal errors would exceed the mentioned limits in no more than 1.6% and 0.1% of cases, respectively. This extensive mode of adjustment became, however, increasingly ineffective with higher demands for occlusal accuracy. CONCLUSION: Complete mean value setting is associated with a relatively low risk of occlusal errors exceeding tolerance limits that are widely accepted in practice. Compared to mean value setting, facebow registration of condylar angle and relations yields no profitable improvement of occlusal accuracy. PMID- 11203645 TI - Long-term marginal periimplant bone loss in edentulous patients. AB - PURPOSE: The aim of this study was to examine the long-term periimplant bone loss in patients treated with implant-supported fixed prostheses in both jaws. MATERIALS AND METHODS: The participants comprised 44 edentulous patients who have been followed for a 15-year period after treatment with a fixed implant-supported prosthesis in the mandible. Thirteen of them also received an implant-supported fixed prosthesis in the maxilla, on average 4.5 years after the mandibular treatment. The periimplant bone level was measured on intraoral radiographs. RESULTS: The long-term results of the implant treatment were successful, and only 1% (3/273) of the implants were lost in the mandible and 7% (5/75) in the maxilla. All but one of the failures occurred before the connection of the prostheses. The mean marginal bone loss around the implants was small (less than 1 mm for a 10-year period after implant placement), and was of similar magnitude in both jaws. However, the individual variation was relatively great. There was no significant difference in marginal bone loss between those who had a maxillary complete denture during the entire observation period and those who had received a fixed implant-supported maxillary prosthesis. Smokers lost more periimplant bone than did the nonsmokers; the difference was significant in the mandible but small and nonsignificant in the maxilla. CONCLUSION: The long-term periimplant bone loss was small and of similar magnitude in the mandible and the maxilla in subjects who had received implant-supported fixed prostheses in both jaws. The prosthetic status in the maxilla, i.e., complete denture or fixed implant supported prosthesis, had no significant influence on the mandibular periimplant bone loss. PMID- 11203648 TI - Changes in the provision of implant-supported prostheses at the Academic Centre for Dentistry Amsterdam (ACTA) from 1989 to 1995. AB - PURPOSE: Over the last decade, oral implantology has become a major treatment modality to aid the restoration of reduced dentitions. The present study monitored and quantified changes within a 5-year interval (1989-1991 [denoted as 1990*] to 1995) in the provision of different types of implant-supported superstructures and characteristics of recipient patients at the Academic Centre for Dentistry Amsterdam (ACTA). MATERIALS AND METHODS: All patients who received oral implants in 1990* and in 1995 were selected, and their files (95 and 105, respectively) were consulted. Data of interest were retrieved retrospectively, compared, and statistically analyzed using Chi-squared tests. RESULTS: A number of statistically significant differences was apparent between these 2 periods. By 1995 there was a threefold increase in both the number of patients and the number of implants placed per year. The patient group of < or = 40 years of age had significantly increased, from 7% to 23%. Also, in 1995 more maxillae were implanted than in 1990* (44% vs 26%). Whereas the majority of implanted patients was edentulous in 1990* (64%), the majority in 1995 was partially edentulous (60%). By 1995, the new technique of guided bone regeneration (GBR) using membranes was evidenced (no GBR in 1990* vs 33% of all patients in 1995 receiving some form of local GBR therapy). With respect to the type of superstructures, there was a strong increase in the number of single-tooth replacements (from 4% to 23%). In the edentulous group, the majority of superstructures in 1990 was fixed prostheses (64%), whereas in 1995 the majority was overdentures (71%). CONCLUSION: Major changes in oral implantology treatments were noticed between the 1990* and 1995 periods at ACTA. There is a trend toward implanting younger patients for partial implant-supported reconstructions using more regenerative procedures and with a more equal distribution in the maxilla and mandible. PMID- 11203649 TI - Fatigue behavior of the zinc-phosphate cement layer. AB - PURPOSE: Fatigue behavior of luting cement film between model fixed partial dentures (FPD) and their dies was investigated to gain a better understanding of the mechanical properties of zinc-phosphate cement. MATERIALS AND METHODS: Fifty six brass dies were made, half of them with grooves and half without grooves. A cantilever FPD for each die was cast in Au-Pd-Ag alloy. Four linear strain gauges were attached to the marginal portions of each retainer. The FPDs were cemented to the dies using zinc-phosphate cement. A fatigue test machine was used to cyclically load the specimens with 50 or 100 N for 5.5 x 10(5) cycles (1 Hz) in 37 degrees C water. During the fatigue test, strain measurements were made after every 0.5 x 10(5) load cycles to discover if strain response was altered. After completion of the fatigue test, ultimate tensile strength of each specimen was measured and statistically analyzed by 2-way analysis of variance. RESULTS: With or without grooves, strain responses were the same at every periodic strain measurement throughout the 50-N fatigue test. For the 100-N fatigue test, strain responses for the specimens without grooves were different before and after cyclic testing, but there was no difference for the specimens with grooves. There were no significant differences in tensile strength among the specimens after the fatigue tests. CONCLUSION: No fatigue fracture was observed in zinc-phosphate cement film after repetitive loading. Repetitive loading may improve stress transmission within the zinc-phosphate cement film. PMID- 11203650 TI - Body movement during sleep in subjects with long-standing bruxing behavior. AB - PURPOSE: This study aimed to determine whether patients with long-standing nocturnal bruxing behavior present different body movement activity during sleep compared with healthy subjects. MATERIALS AND METHODS: Eleven bruxers and 8 nonbruxers were studied in the sleep laboratory, and motor activity was detected with sensor pads placed under the mattress. Movements simultaneously recorded on videotapes were classified according to their duration and grouped in different types according to their characteristics. RESULTS: Subjects with bruxism had significantly more movements during sleep compared with controls; the difference was especially obvious for movements of short duration (< 5 seconds). The differences became significant from the fourth hour of sleep. These short movements were twitches, jerks, or any sudden, brusque movements of the extremities, but without the periodicity encountered in, for example, periodic limb movements during sleep. No significant relationship was found between the occurrence of masseter activity and movements. CONCLUSION: The findings suggest that subjects with nocturnal bruxism have movement disorders that are expressed not only as grinding or clenching of the teeth, but also as an increase of short duration body movements during sleep. This reinforces the hypothesis of a central etiology common to both bruxism and short movements during sleep. PMID- 11203651 TI - Effect of 180-week water storage on the flexural properties of E-glass and silica fiber acrylic resin composite. AB - PURPOSE: The aim of this study was to determine the effect of long-term water immersion on the flexural properties of fiber-reinforced composite. MATERIALS AND METHODS: Continuous, woven, silanized E-glass fibers and woven silica fibers were used to reinforce heat-cured and autopolymerized denture base polymers. Fibers were oriented at a 45-degree angle to the long axis of the test specimens. Control specimens were unreinforced. Dry test specimens and those stored in water for up to 180 weeks were tested with a 3-point loading apparatus. RESULTS: Ultimate transverse strength and flexural modulus of unreinforced and fiber reinforced composite test specimens decreased during water storage (P < 0.001, analysis of variance). Post hoc analysis revealed that after the storage of 4 weeks no statistically significant reduction occurred. CONCLUSION: The results of this study suggest that the ultimate transverse strength of the fiber-reinforced composite made from E-glass fibers is reduced by approximately 27% compared to the dry fiber-reinforced composite. The majority of the reduction occurred during 4 weeks of storage in water and remained approximately at that level for 180 weeks. PMID- 11203652 TI - Within-subject comparison between connected and nonconnected tooth-to-implant fixed partial prostheses: up to 14-year follow-up study. AB - PURPOSE: This long-term follow-up study aimed to compare the outcome of fixed prostheses supported by teeth and implants and by freestanding implants only. MATERIALS AND METHODS: From prosthesis insertion up to 14 years (mean 6.5 y), 18 patients were followed. Implant-supported prostheses with and without tooth connection were compared within the same jaw. The tooth-implant prostheses were supported by 30 implants and 30 teeth, and the freestanding prostheses were supported by 48 implants. Implant outcome, marginal bone stability, and mechanical complications were recorded. RESULTS: Neither implant mobility nor fractures of any component of the implants were observed. No prosthesis complications were observed, and the same applied for crown cement failure and intrusion of teeth. Only one periapical lesion was detected at the first follow up. The annual change of the marginal bone level around connected and freestanding implants did not differ significantly. The mean marginal bone loss (over the 2 groups) for the first 6 months amounted to 1.08 mm. After the first 6 months, an annual marginal bone loss of 0.015 mm was observed. There was no difference between the 3 connection types (single implant connected to single tooth, multiple implants and/or multiple teeth connected with single connector, and multiple connectors) for the first 6 months or thereafter. The marginal bone loss (over the 3 groups) for the first 6 months was 1.15 mm. After the first 6 months, the annual bone loss (over the 3 groups) amounted to 0.015 mm. CONCLUSION: Based on the results of this study, splinting teeth with implants for implant-supported fixed prostheses did not affect the long-term outcome in comparison to freestanding implants. PMID- 11203653 TI - Bond strength of luting cements to zirconium oxide ceramics. PMID- 11203654 TI - New advances in implant dentistry. PMID- 11203655 TI - Application of capacitively coupled electric field enhances periimplant osteogenesis in the dog mandible. AB - PURPOSE: Expeditious postoperative ingrowth of bone into dental implants is desired for clinically successful fixation of oral implants. The present study was performed to evaluate the effect of applying a capacitively coupled electric field (CCEF) on periimplant osteogenesis in the dog mandible. MATERIALS AND METHODS: Twelve adult male beagles were used in this study. All of the premolars on both sides of the mandible were removed from each dog. A POI (Ti-6Al-4V) 3 piece implant (3.7 mm in diameter and 8.0 mm in length) whose surface had been treated with anodic oxidation was placed into each test site by self-tapping. Daily application of CCEF (8 h/day) was initiated on the day following the surgery and was continued through the day of sacrifice. A CCEF was induced by an external source delivering 10-Vp-p, 60-kHz sine-wave signals through an oral electrode plate. One side of the mandible of each dog was treated with CCEF, while the other side was not. On the control side, an oral electrode plate was attached for 8 hours per day, but CCEF was not applied. The effect of daily application of CCEF on the ingrowth of bone into the implant was examined at 14, 21, or 30 days after implant placement. A fourth control group was not treated with CCEF and was maintained for 90 days to confirm that CCEF treatment enhances bone ingrowth in dental implants. RESULTS: Daily application of CCEF significantly increased the bone-contact ratio at days 14, 21, and 30 after implant placement in comparison with the respective controls. The bone-area ratios of the 14- and 21-day CCEF-treated groups were significantly larger than those of the respective controls and were similar to those of the 90-day control group. CONCLUSION: CCEF treatment increases periimplant osteogenesis in the dog mandible, confirming its usefulness in oral implantology. PMID- 11203656 TI - A preliminary study on a resin-modified glass-ionomer cement for transitional restorations and subsequent core buildups. AB - PURPOSE: The purpose of this study was to evaluate the serviceability of a resin modified glass-ionomer cement for transitional restorations and subsequent core buildups in endodontically treated maxillary premolars. MATERIALS AND METHODS: Fifty Vitremer restorations were made in 42 patients by one operator during a period of 5 months. After 1 year of follow up, the quality of the restorations was assessed for the variables occlusal contacts, proximal contacts, marginal adaptation, and surface roughness. Survival was estimated at 2 years of service either as a transitional restoration or as a core buildup. RESULTS: The percentage survival of the transitional restorations was 85% +/- 6%. When the crowned Vitremer restorations were added to the transitional restorations, the 2 year survival was 98% +/- 2%. With respect to the quality assessment, the majority of the restorations showed either no or light occlusal contacts and no or light contacts on at least one of their proximal surfaces. Marginal integrity and surface roughness were considered to be suboptimal on average. CONCLUSION: The described restorations seem to perform adequately for a transitional period of 1 to 2 years. Their viability as substructures for permanent cast restorations remains to be tested in long-term clinical studies. PMID- 11203657 TI - Effect of the addition of poly(methyl methacrylate) beads on some properties of acrylic resin. AB - PURPOSE: There have been numerous attempts to improve the mechanical properties of acrylic resin. However, the fracture of dentures is still an unresolved problem. The potential advantage of self-reinforcement should be improved mechanical properties over the amorphous random polymer. This study investigated the addition of poly(methyl methacrylate) (PMMA) beads in a variety of percentages on a range of mechanical properties of PMMA denture base acrylic resin. MATERIALS AND METHODS: The transverse and impact strengths and hardness of acrylic resin specimens stored in water for periods of 1 week and 6 months prior to testing were investigated. RESULTS: The results showed that for specimens stored for 1 week, the addition of up to 25% beads produced a significant increase in the modulus of elasticity. Addition of 5% beads produced a slight but nonsignificant increase in the modulus of rupture, although additions of increasing percentages produced a decrease in the modulus of rupture. The impact strength was increased for 5% to 25% beads and decreased for 40% beads. The hardness showed only small changes. For specimens stored in water for 6 months, the modulus of rupture decreased with increasing percentages of beads. The addition of beads up to 10% significantly increased the modulus of elasticity. There was no significant increase in impact strength but a significant increase in hardness for 5% beads. CONCLUSION: The addition of PMMA beads to acrylic resin did not produce a substantial improvement in the mechanical properties and cannot be recommended as a method of reinforcement in its present form. PMID- 11203658 TI - Effect of surface treatments on the bond strength between composite resin and acrylic resin denture teeth. AB - PURPOSE: This investigation studied the effects of 3 surface treatments on the shear bond strength of a light-activated composite resin bonded to acrylic resin denture teeth. MATERIALS AND METHODS: The occlusal surfaces of 30 acrylic resin denture teeth were ground flat with up to 400-grit silicon carbide paper. Three different surface treatments were evaluated: (1) the flat ground surfaces were primed with methyl methacrylate (MMA) monomer for 180 seconds; (2) light-cured adhesive resin was applied and light polymerized according to the manufacturer's instructions; and (3) treatment 1 followed by treatment 2. The composite resin was packed on the prepared surfaces using a split mold. The interface between tooth and composite was loaded at a cross-head speed of 0.5 mm/min until failure. RESULTS: Analysis of variance indicated significant differences between the surface treatments. Results of mean comparisons using Tukey's test showed that significantly higher shear bond strengths were developed by bonding composite resin to the surfaces that were previously treated with MMA and then with the bonding agent when compared to the other treatments. CONCLUSION: Combined surface treatment of MMA monomer followed by application of light-cured adhesive resin provided the highest shear bond strength between composite resin and acrylic resin denture teeth. PMID- 11203659 TI - In vitro fracture force and marginal adaptation of ceramic crowns fixed on natural and artificial teeth. AB - PURPOSE: Artificial teeth made of acrylic resin or alloy are considered substitutes for rare caries-free human teeth in in vitro examinations. The purpose of this study was to compare the fracture strength and marginal adaptation of all-ceramic single crowns fixed to natural teeth with crowns fixed to artificial teeth after artificial aging. MATERIALS AND METHODS: The fracture force and marginal adaptation were investigated in 28 adhesively luted all ceramic crowns on human molars of different sizes, as well as on alloy and liquid crystal polymer (LCP) artificial teeth. The fracture force was determined using a universal testing machine, and the semiquantitative marginal adaptation was examined using a scanning electron microscope, in both instances after simulating 5 years of clinical service. RESULTS: Fracture force was found to be significantly higher for crowns fixed on substitute materials (alloy = 1,838 N; LCP = 1,392 N) than for crowns on human teeth (888 N). No significant differences in marginal quality could be determined between the groups. All crowns showed marginal gaps of about 10% and perfect margins at about 90%. CONCLUSION: The high in vitro fracture values of all-ceramic crowns on artificial materials may lead to a misinterpretation of the tested restorative materials, overvaluing the material properties in a first preclinical estimation. Human teeth or materials with a comparable modulus of elasticity are therefore preferred in in vitro fracture tests. PMID- 11203660 TI - Changes in signs and symptoms of temporomandibular disorders following treatment with implant-supported fixed prostheses: a prospective 3-year follow up. AB - PURPOSE: The aim was to investigate whether the replacement of lost teeth with implant-supported fixed prostheses (IFP) had any influence upon the signs and symptoms of temporomandibular disorders (TMD). MATERIALS AND METHODS: The subjects comprised 78 consecutive patients referred to a specialist clinic for treatment with IFPs. All were examined with respect to the presence of signs and symptoms of TMD before the start of treatment and after 1 and 3 years. RESULTS: Before treatment began, 21% of the patients were found to have moderate (15%) or severe (5%) clinical signs of dysfunction according to the Helkimo index. These figures decreased numerically but not statistically significantly to 10% and 1%, respectively, at the 3-year follow up. Nearly half of the patients (45%) reported one or more subjective symptoms of TMD at the first examination. The anamnestic index used had decreased statistically significantly at the 3-year follow up, when the 5 variables composing the index had improved, but the improvement was statistically significant only for the variables joint sounds and pain when opening the mouth wide. All patients were satisfied with the treatment received. CONCLUSION: The results from the present investigation show that treatment with IFPs has a good and lasting effect on the functional status of the masticatory system as well as on subjective symptoms of TMD and chewing ability in the vast majority of patients treated. PMID- 11203661 TI - Tomographic evaluation of TMJ loading affected by occlusal pivots. AB - PURPOSE: The purpose of this study was to clarify the direction and magnitude of condyle displacement during clenching with occlusal pivots. Temporomandibular joint (TMJ) loading and flexibility and the clinical significance of orthopedic appliance therapy are also discussed. MATERIALS AND METHODS: Participants were 16 volunteers with a mean age of 25.8 years. Maxillary and mandibular flat occlusal devices were fabricated. TMJ tomogram series were taken first with tripod support and then with maxillary clenched anterior pivot support and/or unilateral posterior pivot support. Condyle positions on the TMJ tomograms were analyzed using the digital subtraction technique. RESULTS: When clenching with the anterior pivot, the anterior reference point (A) on the mandibular condyle was translated 0.1 mm posteriorly (P > 0.05) and 0.2 mm superiorly (P < 0.01) from the tripod-support reference point. In the case of the ipsilateral posterior pivot, point A was rotated 1.2 degrees (P < 0.01) and was translated 0.4 mm (P < 0.01) posteriorly and 0.18 mm superiorly (P > 0.05). CONCLUSION: Condyle displacement during clenching with the anterior and posterior unilateral pivot was found, which supports previous findings. However, the direction and magnitude of the displacement differed from those of previous studies using jaw-tracking devices, and individual values differed greatly among subjects. PMID- 11203662 TI - Comparison of marginal fit of 3 different metal-ceramic systems: an in vitro study. AB - PURPOSE: The aim of this study was to compare the marginal adaptation of metal ceramic crowns made with 3 different metal substructures. MATERIALS AND METHODS: Seventy-five gypsum dies were fabricated from a master steel die. They were randomly divided into 3 groups of 25 dies each. A metal coping was prepared on each die using a different technique for each group: composite alloy, electroforming, and cast high-noble alloy. Ceramic was baked on all of the samples following the same protocol and simulating the shape and size of a maxillary central incisor. All specimens were evaluated under a stereomicroscope at 200x magnification. The marginal gap was measured at 8 different points on each specimen before and after ceramic application and also on the master steel die. A total of 3,600 measurements was evaluated. The results were statistically elaborated by means of a t test and one-way analysis of variance (ANOVA). RESULTS: The ANOVA revealed a significant difference in mean marginal gap before and after ceramic application within each group. Electroforming (mean 32 microns) and high-noble alloy (mean 31 microns) showed better marginal fit after ceramic application and on the master steel die compared to composite alloy (mean 68 microns; P < 0.0001). CONCLUSION: Marginal gaps are influenced by the application of ceramic and by the alloy used for the substructure, and the values obtained were within the limits of clinical acceptability (70 microns). PMID- 11203663 TI - Long-term analysis of biologic and technical aspects of fixed partial dentures with cantilevers. AB - PURPOSE: The aim of the present clinical study was to analyze the long-term treatment outcome of fixed partial dentures (FPD) with cantilevers. MATERIALS AND METHODS: Ninety-two patients with 115 cantilever FPDs on 239 abutment teeth were examined. Immediately following cementation, radiographs of the abutment teeth were obtained. At the follow-up examination 5 to 16 years after cementation, the abutment teeth were clinically and radiographically evaluated. Besides the assessment of periodontal parameters and vitality testing, the presence of carious lesions of the abutment teeth, loss of retention, fracture of bridgework, and fracture of abutment teeth were also recorded. The Student's t test was used to detect differences between abutment teeth and control teeth with natural crowns as well as over time within the groups. RESULTS: Plaque scores and bleeding on probing were low at both abutment and nonabutment teeth. Mean probing pocket depth and level of the clinical attachment never exceeded 3.0 mm in both groups. The radiographic bone levels at abutments were stable within 3% over the observation period. Of the 120 initially vital abutment teeth, 12 (10%) lost vitality during the observation period; one (1%) of the 119 initially nonvital abutments showed periapical pathology. Development of secondary caries was observed at 8% of the 239 abutment teeth. In total, 8% of the abutment teeth were affected by loss of retention, which made up more than half of all technical problems. Material fractures only occurred occasionally, affecting from 1% to less than 3% of the abutment teeth. Fracture of abutment teeth amounted to 3% and was twice as frequent at abutments adjacent to cantilevers compared to abutments not adjacent to cantilevers. CONCLUSION: The most frequent biologic (caries) and technical complications (loss of retention) made up more than half of all problems recorded. These problems may be at least partially avoided by performing optimal plaque control and by strictly observing the rules for preparation of retentive FPD abutments. PMID- 11203664 TI - Properties of an experimental mouthguard material. AB - PURPOSE: The purpose of the present study was to evaluate some important mechanical properties of an experimental silicone material (PM1) to assess its potential as a mouthguard material. MATERIALS AND METHODS: The hardness, tear strength, tensile properties, and energy absorption properties of the silicone material were determined and compared with those of 2 commercially available materials (Bioplast, a polyvinylacetate polyethylene, and Polyshield, a silicone). RESULTS: Bioplast was significantly harder than Polyshield and PM1. Polyshield was significantly harder than PM1. Bioplast had a significantly higher tear strength than both Polyshield and PM1. The tensile strength of Bioplast was significantly greater than that of Polyshield and PM1. PM1 had a significantly higher tensile strength than Polyshield. Bioplast had a significantly lower energy absorption capacity at 500 N than both Polyshield and PM1, with PM1 having a significantly higher value than Polyshield. At 1,000 and 1,500 N, Bioplast had a significantly higher energy absorption than both Polyshield and PM1. CONCLUSION: It was concluded that PM1 showed better energy absorption properties than Polyshield and better energy absorption properties than Bioplast at lower impact forces. PM1 was softer and had better tear and tensile properties than Polyshield. The results of the present study suggest that the new material has a good potential for use as a mouthguard material. PMID- 11203665 TI - Probability of fracture of all-ceramic crowns. AB - PURPOSE: The study compared the probability of fracture of 4 systems of all ceramic crowns fabricated on maxillary central incisors. MATERIALS AND METHODS: The 4 all-ceramic crown systems were: (1) a glass-infiltrated, sintered alumina system (In-Ceram) fabricated conventionally, (2) the same system with machine milled alumina cores (CEREC 2), (3) a heat-press, leucite-reinforced glass ceramic system (IPS Empress), and (4) a high-purity, high-density alumina system (Procera). Ten crowns of each system were fabricated and compressed at 45 degrees at the palatal surface until failure. The data were analyzed with the Weibull method. RESULTS: There were no significant differences in the probability of fracture among the 4 systems studied. CONCLUSION: The likelihood of fracture of these crown systems on central incisors should be similar. PMID- 11203666 TI - Retention of a posterior resin-bonded fixed partial denture with a modified design: an in vitro study. AB - PURPOSE: The aim of this study was to test in vitro the resistance of a modified resin-bonded fixed partial denture (RBFPD) to detachment using a laboratory setup simulating load fatigue of mastication forces. The effect of varying the cement type was also investigated. MATERIALS AND METHODS: Extracted teeth were used to prepare specimens each consisting of a premolar and a molar with a space equivalent to a molar in between. Five test groups were prepared (n = 7). Specimens in group 1 were prepared to receive conventional RBFPDs with proximal grooves, occlusal rests, and lingual wings. Specimens in groups 2 and 3 were prepared to receive modified RBFPDs with retentive-slot restorations. Specimens in group 4 were prepared to receive RBFPDs with retentive-slot restorations only, whereas specimens in group 5 were prepared similarly to the ones in groups 2 and 3 but with inlay preparations instead of the retentive slots. Castings were made and their fit surfaces microetched. In groups 1, 2, 4, and 5 castings were cemented with Cement-It, whereas castings of group 3 were cemented with Panavia 21. Slot cavities of groups 2, 3, and 4 were restored with a resin composite. Specimens were subjected to compressive load cycling for 230,000 cycles at 4 Hz under water. Castings were then separated from the abutments under tensile loading. RESULTS: Mean separation forces were: group 1 = 361 N, group 2 = 525 N, group 3 = 562 N, group 4 = 449 N, and group 5 = 417 N. Groups 2 and 3 had significantly higher mean separation forces than groups 1 and 5. Separation of castings in groups 2 and 3 was associated with a higher frequency of cohesive fracture of the abutments than in group 1. Adhesive failure was uncommon among specimens of groups 2, 3, and 4. CONCLUSION: The modified RBFPDs of groups 2 and 3 had better potential for retention. Increased resistance to dislodgment of the modified RBFPDs was not directly related to the surface area of the castings, nor was it related to the type of resin cement, but rather to mechanical interlocking of the castings with the retentive-slot resin composite restorations. PMID- 11203667 TI - Impact of implant interdependency when evaluating success rates: a statistical analysis of multicenter results. PMID- 11203668 TI - Dental research and prosthodontics. PMID- 11203669 TI - Correlation between clinical scoring of secondary caries at crown margins and histologically assessed extent of the lesions. AB - PURPOSE: The aim of this study was to propose a new clinical diagnostic rating index for secondary caries lesions at crown margins and to correlate this index with histologic evaluations. MATERIALS AND METHODS: Based on criteria for the evaluation of root caries, a modification of secondary caries lesions at the crown margin (SC index) was applied; the lesion characteristics were described as SCO to SC4. A total of 16 crowned teeth exhibiting secondary caries were randomly selected. The teeth were rated and grouped according to their clinical SC grades (SC1 to SC4). After embedding in Technovit, the teeth were serially sectioned and histologic caries scores were given for each section. RESULTS: Fifty-two percent of the prepared margins were in cementum/dentin. Crown margins with no caries lesions were mainly found in teeth clinically rated as SC1 and exhibiting localized discolorations, whereas deep lesions were found histologically at teeth rated SC4. The nonparametric test according to Spearman's rank correlation coefficient (rho) confirmed a highly significant correlation between the clinical SC index and the histologic evaluation (rho = 0.87, 95% confidence interval = 0.67 to 0.96, P < 0.01). SC1 discolorations overestimate caries lesions, whereas SC2 and SC4 lesions are well correlated to the percentage of histologically evaluated caries extension into all sections of a tooth. Lesions rated SC3 demonstrated a high variability of caries penetration into the dentin. CONCLUSION: The depth of discolorations and circular lesions is clinically not well predictable. Clinical diagnosis for localized superficial caries and deep caries lesions at the crown margin correlated well with the histologic caries rating. PMID- 11203670 TI - Resin-bonded fixed partial dentures--a literature review with presentation of a novel approach. AB - PURPOSE: Resin-bonded fixed partial dentures (RBFPD) have been in our profession for over 20 years. The aim of this work was to provide some background about their development and the factors that influence their clinical longevity. MATERIALS AND METHODS: A recent literature search conducted using MEDLINE along with analysis of bibliographies of published papers revealed a considerable number of publications of RBFPDs since their first introduction in the mid-1970s. Critical analysis of these publications revealed some important and interesting key facts. These were divided into sections about developments in the treatment of the fit surface of the casting, bonding systems, and prosthesis design. A separate section about factors that affect the longevity of RBFPDs is included, along with a detailed description of preparation designs of an anterior and a posterior RBFPD. RESULTS: The typical design of RBFPDs is characterized by a high degree of conservation of tooth structure of abutments compared with designs of conventional fixed prostheses. While the early RBFPDs were associated with a high frequency of premature failure--mostly because of debonding--developments in preparation design and bonding techniques as well as better understanding of the appropriate type of metal alloy to be used and the best preparation method for enhanced bonding have led to significant improvements in their long-term survival. CONCLUSION: RBFPDs should be considered viable treatment options for those clinical situations that are best suited for their use. Preparation design, cement type, and casting alloy type as well as surface treatment are among the most important factors that influence longevity of RBFPDs. PMID- 11203671 TI - Strength and microstructure of IPS Empress 2 glass-ceramic after different treatments. AB - PURPOSE: This investigation was designed to determine whether heat pressing and/or simulated heat treatments affect the flexure strength and microstructure of the lithium disilicate glass-ceramic of the IPS Empress 2 system. MATERIALS AND METHODS: Four groups of the lithium disilicate glass-ceramic were prepared as follows: group 1 = as-received material; group 2 = heat-pressed material; group 3 = heat-pressed and stimulated initial heat-treated material; and group 4 = heat pressed and simulated heat-treated material with full firings for a final restoration. Three-point bending tests and scanning electron microscopy (SEM) analysis were conducted. RESULTS: The flexure strength of group 2 was significantly higher than that of group 1. However, there were no significant differences in strength among groups 2, 3, and 4, or between groups 1 and 4. The SEM micrographs of the lithium disilicate glass-ceramic showed a closely packed, multidirectionally interlocking microstructure of numerous lithium disilicate crystals protruding from the glass matrix. The crystals in the glass matrix of the heat-pressed materials (groups 2, 3, and 4) were a little more homogeneous and about 2 times bigger than those of the as-received material (group 1). These changes of the microstructure were greatest between groups 1 and 2. However, there were no marked differences among groups 2, 3, and 4. CONCLUSION: Although there were significant increases in the strength and some changes of the microstructure after the heat-pressing operation, the combination of heat pressing and simulated subsequent heat treatments did not produce an increase of strength of IPS Empress 2 glass-ceramic. PMID- 11203672 TI - Two-body wear of dental composites under different loads. AB - PURPOSE: Although dental composites are excellent for restoring the appearance of natural tooth tissues, their relatively poor resistance to wear, especially in approximal and occlusal contact areas, is still a major source of concern. The aim of this research was to study a basic wear mechanism, under 2-body wear conditions, that may be integrated into our understanding of the in vitro and in vivo wear behavior of dental composites. MATERIALS AND METHODS: An in vitro 2 body wear test was conducted on 2 selected ultrafine compact-filled dental composites under different magnitudes of sinusoidal cyclic load. The wear surfaces and cross sections of the wear layers were assessed using scanning electron microscopy (SEM) to explore the nature of the wear pattern of the dental composites under cyclic loading conditions. RESULTS: The wear losses of both composites increased with load. SEM analysis of wear surfaces and subsurface sections indicated that the composites tested displayed different wear mechanisms from low to high loads. An explanation for the wear pattern is proposed based on the observed wear behavior. CONCLUSION: The in vitro wear pattern of the ultrafine compact-filled dental composites tested is closely related to the applied load. Although the wear loss increased in a roughly linear relationship with applied load, the underlying wear mechanism involved may experience a significant change from low to high load conditions during wear. PMID- 11203673 TI - Vertical position, rotation, and tipping of molars without antagonists. AB - PURPOSE: There has been a general belief that permanent teeth without antagonists overerupt, creating, after some time, considerable clinical problems. However, very few studies in the literature support this statement. The purpose of this investigation was to examine the position of molars that had been unopposed for a long period and to test the hypothesis that overeruption does affect every tooth without an antagonist. MATERIALS AND METHODS: Fifty-three individuals were examined clinically, and dental casts were taken to evaluate the position of unopposed molars. There were 84 molars (61 in the maxilla and 23 in the mandible) with a documented period of at least 10 years without antagonists. Among these teeth, 25 molars had neither an antagonist nor a mesially adjacent tooth. A qualitative method was used to evaluate the position of the molars in the vertical direction: (1) teeth with no sign of overeruption, (2) teeth with slight overeruption (< 2 mm), and (3) teeth with moderate to severe overeruption (> or = 2 mm). RESULTS: Of the 84 molars examined, 15 teeth (18%) revealed no signs of overeruption, 49 teeth (58%) displayed overeruption of less than 2 mm, and 20 teeth (24%) showed moderate to severe overeruption. Individuals with molars that had lost their antagonists in adult age had a lower risk for overeruption than the other subjects examined. The existence of adjacent teeth was important for the position of the unopposed molar in a mesiodistal or buccolingual direction. Molar rotation was more frequent in the maxilla, whereas tipping was more common in the mandible. CONCLUSION: It is concluded that not all molars without antagonists overerupt, not even in a long-term perspective. PMID- 11203675 TI - Effects of attachment type on the mobility of implant-stabilized overdentures--an in vitro study. AB - PURPOSE: To stabilize overdentures, a wide range of attachments to implants is suggested. Although there is evidence that denture stability is an important factor for patient satisfaction, there are no data on how these attachments may reduce denture mobility. It was the purpose of this study to compare the effects of different types of attachments on the mobility of implant-stabilized overdentures in vitro, designing a measurement device that could also be used in vivo. MATERIALS AND METHODS: On an acrylic model with 2 implants in the canine areas, magnets were fixed to one of the implant abutments. Four Hall-effect devices were attached to the denture opposite the magnet, which allowed contact free measurements of denture movements. RESULTS: In vitro experiments loading an overdenture showed very small, largely insignificant differences in denture mobility when different bar or ball attachments were used. Geometric aspects of load application were more important than the choice of attachment. CONCLUSION: The measurements gave no guide to the choice of an attachment. The similarity of the attachments must be confirmed by in vivo measurements. PMID- 11203674 TI - Water sorption and dimensional changes of denture base polymer reinforced with glass fibers in continuous unidirectional and woven form. AB - PURPOSE: The aim of this study was to determine the dimensional accuracy and water sorption of a denture base polymer that was reinforced with glass fibers in continuous unidirectional and woven form in different weight fractions. MATERIALS AND METHODS: Ten rhombic brass plates were prepared with reference points, and 70 heat-cured denture base polymer specimens were produced using these brass models. Ten of 70 were used for controls, and 60 were reinforced with glass fibers in continuous parallel and woven form. The dimensional changes of polymer and fiber reinforced composite specimens after processing, drying for 4 days at 37 degrees C, and storage in 37 degrees C water for 90 days were calculated by the change of the distance vector. The measurements were made between the reference points on the specimens and were compared with those on the brass model at 4 different stages. The water sorption calculations were made at 10 different time intervals on 70 specimens, which were immersed in a 37 degrees C distilled water bath and weighed. RESULTS: The polymerization shrinkage and water sorption of denture base polymers is lower when the specimens are reinforced with glass fibers in continuous unidirectional and woven form. The highest fiber content showed the smallest dimensional change (0.069 mm, or 0.25%), and the unreinforced group showed the largest change (0.139 mm, or 0.54%). Water sorption occurred mainly during the first 14 days. CONCLUSION: As the fiber content increases, the dimensional change and water sorption decrease. PMID- 11203676 TI - Immediate effect of occlusal contact pattern in lateral jaw position on the EMG activity in jaw-elevator muscles in humans. AB - PURPOSE: The aim of this study was to investigate the effect of experimental alterations of nonworking-side occlusal contacts on jaw-elevator muscle activity. MATERIALS AND METHODS: Individual devices were fabricated to simulate various lateral occlusal relationships. Twelve human subjects were asked to carry out submaximal lateral clenching, and electromyographic (EMG) activity of the masseter and anterior and posterior temporalis muscles was measured. RESULTS: Clenching in a lateral mandibular position under natural conditions induced an activity pattern with a clear dominance of the anterior and posterior temporalis muscles on the working side. Working-side dominance in the anterior temporalis was reduced moderately when an experimental nonworking-side occlusal contact was added. Dominance decreased dramatically when an experimental nonworking-side interference was added. The working-side activity in the posterior temporalis was also reduced dramatically by an experimental nonworking-side interference, but not by a nonworking-side occlusal contact. None of the experimental contact patterns had a significant effect on the masseter activity. CONCLUSION: These results suggest that the nonworking-side occlusal contacts have a significant effect on clenching-induced temporalis muscle activity. PMID- 11203677 TI - Communication during prosthodontic treatment--dentist, patient, and dental nurse. AB - PURPOSE: This study described and explored verbal communication during prosthodontic treatment. MATERIALS AND METHODS: Sixty-one patients and 15 dentists participated. Sixty-one prosthetic treatment periods, during which fixed tooth- or implant-supported prostheses were placed, were followed. One visit during each treatment period was audio recorded. The recorded verbal communication was analyzed with the Roter Interaction Analysis System-dental. The inter-rater reliability was 95% to 97% for utterance classification and kappa = 0.71 to 0.78 for categorization definition. RESULTS: There were 43,663 utterances available for analysis. Of those, 59% was dentist communication, 28% was patient communication, and 10% was dental nurse communication. Other persons, e.g., dental technicians, contributed with 3%. The dentist-patient communication contained more task-focused than socioemotional behaviors. Female patients used socioemotional talk to a greater extent than did the male patients. Dentists and patients of different genders communicated more overall, especially male dentists with female patients. The age difference between dentist and patient had no effect on the amount or type of communication. The dental nurse talked slightly more with male patients. CONCLUSION: When different genders met there was more communication, and the talk was more socioemotional when the patient was female. PMID- 11203678 TI - Functional mandibular deformation in edentulous subjects treated with dental implants. AB - PURPOSE: The purpose of this study was to measure medial convergence, dorsoventral shear, and corporal rotation in the human mandible. MATERIALS AND METHODS: Measurements were made using custom-fabricated strain gauge displacement transducers in 6 edentulous subjects who had been treated with mandibular endosseous dental implants. These were mounted on the most distal of the mandibular implants on each side, and measurements were made in real time using a multichannel analogue/digital converter and a personal computer for data storage and analysis. Measurements were made while the implants were loaded, and the subjects opened and closed their mouths and made lateral mandibular excursions. Medial convergence was measured as a linear change at the site of the most distal implant. Dorsoventral shear was expressed as a relative rotation of the right and left mandibular bodies projected onto the median sagittal plane, and corporal rotation was expressed as the relative rotation of the most distal implant. RESULTS: Jaw deformation was found to occur immediately on opening and was related to closing forces and jaw position. Medial convergence of up to 41 microns was observed, with values for corporal rotation of up to 6 degrees and dorsoventral shear of up to 19 degrees. CONCLUSION: The study demonstrated clinically for the first time 3 different and simultaneous patterns of functional mandibular deformation. PMID- 11203679 TI - Curing efficiency of visible light- and dual-cured denture reliners. AB - PURPOSE: The purpose of this study was to evaluate the curing efficiency of 8 light- and dual-cured denture reliners. MATERIALS AND METHODS: The curing efficiency was measured with Fourier infrared micromultiple internal reflectance spectroscopy, calculating the percentage of remaining carbon double bonds on the top and bottom surfaces of each specimen immediately after exposure to the extraoral light-curing unit according to the manufacturer's instructions and after 1 week of storage in dark and dry conditions. Another group of specimens was photopolymerized initially through a denture base resin prior to the extraoral light-curing polymerization. Five specimens of each reliner were tested. RESULTS: The dual-cured reliners showed no statistically significant differences (P > 0.05) between top and bottom surfaces after immediate exposure to the light-curing unit. On the contrary, light-cured reliners revealed significant differences. The majority of the reliners showed reduction of the percentage of remaining carbon double bonds at both surfaces after 1 week of storage in dark and dry conditions. Photopolymerization of light-cured reliners through a denture base resin induced an increased amount of remaining carbon double bonds, whereas no effect was observed in dual-cured materials. CONCLUSION: Dual-cured denture liners exhibited distinct advantages over light-cured ones concerning the curing efficiency. PMID- 11203680 TI - An investigation of self-reinforced poly(methyl methacrylate) denture base acrylic resin using scanning electron and atomic force microscopy. AB - PURPOSE: The aim of this study was to examine the interfacial region of poly(methyl methacrylate) (PMMA) reinforced with untreated and surface-treated PMMA fibers in both chopped and continuous form using scanning electron and atomic force microscopy. MATERIALS AND METHODS: Acrylic resin specimens incorporating untreated and surface-treated (with butadiene styrene latex emulsion) PMMA fibers were examined using a scanning electron microscope and an atomic force microscope. RESULTS: There was evidence of random arrangement of untreated and surface-treated chopped fibers throughout specimens with areas of dense fiber aggregation and other areas containing few or no fibers. For the untreated and surface-treated fibers in continuous forms (a single and 2 unidirectional layers), there was evidence of fiber displacement and buckling, together with variation in interfiber spacing. For the specimens containing surface-treated continuous fibers in a cross-ply arrangement that had demonstrated a substantial improvement in the modulus of rupture, there was no evidence of fiber buckling, and the layer of butadiene styrene was consistently thin and even in comparison to weaker specimens. CONCLUSION: The thickness of the rubber layer and the fiber arrangement (in terms of fiber displacement and interfiber spacing) may be important factors in the success of the reinforcement. PMID- 11203682 TI - Addictive behaviour of adolescents and young adults. PMID- 11203681 TI - Prosthetic restoration following maxillary resection without an oroantral defect: a case report. PMID- 11203683 TI - Health professions speak out against the confusing messages regarding HIV/AIDS. PMID- 11203685 TI - Bibliography of toxinology. PMID- 11203684 TI - Influence of various cytokines on the expression of CD20 on the surface of CLL cells in vitro. PMID- 11203686 TI - Reoperation results of arterial involvement in Behcet's disease. AB - OBJECTIVES: to retrospectively evaluate the role of vascular interventions in Behcet's disease with arterial involvement. So far, little information is available on the surgical approach for arterial involvement in Behcet's disease. MATERIAL AND METHODS: between February 1989 and August 1997, among 178 patients with Behcet's disease referred to our clinic, vascular involvement was established in total of 67 patients (38%) which consisted of 59 venous (33%) and 12 (7%) arterial involvements requiring urgent surgical intervention. Primary arterial lesions were occlusive in one patient, aneurysm formation in nine or both in four. RESULTS: twelve primary operations and 12 reoperations were performed. The reasons for reoperations were anastomotic aneurysms, graft occlusion, occlusion of native vessel, graft infection, bleeding from anastomosis and aortoenteric fistula. First reoperation was performed after a mean period of 6.4 months (1-15 months). Postoperative follow-up was 12-60 months (mean 36 months) and three patients died during follow-up. CONCLUSIONS: the surgical results were not satisfactory because of progressive graft thrombosis and formation of new aneurysms at the anastomosis. Aggressive medical treatment should be combined when major vessel involvement occurs. All types of arterial punctures for angiography or blood gases should be minimised because of the risk of new aneurysm formation. Surgical intervention is indicated only in patients with a growing aneurysm, acute rupture or severe ischaemia. PMID- 11203687 TI - Evolution of the proportions of two sigma viral types in experimental populations of Drosophila melanogaster. PMID- 11203688 TI - ACOG committee opinion. Maternal phenylketonuria. Committee on Genetics. PMID- 11203689 TI - Intrauterine growth restriction. Clinical management guidelines for obstetrician gynecologists. American College of Obstetricians and Gynecologists. PMID- 11203690 TI - [Functional imaging of the auditory cortex: role of magnetoencephalography]. AB - We present the different methods for detecting cerebral activity in the auditory cortex. Positron emission tomography (PET) and functional MRI (fMRI) measure such activity indirectly by calculating the blood flow rate or the consumption of oxygen. The direct methods of detection record the electrical or magnetic activity by eletroencephalography (EEG), or magnetoencephalography (MEG), respectively. The aim of this study was to define the role of MEG amongst these different techniques using the data from recordings of evoked magnetic fields in 5 healthy subjects. The localizations demonstrated the tonotopic organization of the auditory cortex, with high-pitched sounds showing a more medial cortical projection than low-pitched sounds. These various techniques are complementary. PET allows a pharmacological study of the cortex, and could be used in patients with cochlear implants. FMRI is non-invasive, and has a high spatial resolution. EEG has an excellent temporal resolution, and EEG recordings do not require major equipment or infrastructure. MEG has a better spatial resolution, with the same temporal resolution, as EEC. MEG is particularly useful in the localization of the cortical generators of middle-latency auditory evoked responses. PMID- 11203691 TI - [Parkinson's disease: diagnostic and therapeutic criteria. Short text]. PMID- 11203692 TI - Bibliography. Current world literature. Benign prostatic hyperplasia. PMID- 11203693 TI - Bibliography. Current world literature. Urinary tract infections and sexually transmitted diseases. PMID- 11203694 TI - Skin cell induction of calcitonin gene-related peptide in embryonic sensory neurons in vitro involves activin. AB - Target skin cells induce the neuropeptide calcitonin gene-related peptide (CGRP) in naive embryonic dorsal root ganglion (DRG) neurons in vitro, but the molecular basis of that induction is not known. Recombinant activin or bone morphogenetic proteins (BMPs) dramatically increase the number of sensory neurons with CGRP and substance P in vitro (X. Ai et al., 1999, Mol. Cell. Neurosci. 14, 506-518). These experiments were designed to test if activin or BMPs accounted for the CGRP inductive activity by skin cells. To identify factors from skin that induce CGRP, we developed a bioassay in which embryonic DRG neurons isolated before peripheral target contact in vivo are challenged in vitro with specific factors. Conditioned medium from an embryonic rat skin cell line induced neuronal CGRP expression, and induction was blocked by follistatin, implicating transforming growth factor family members. Immunoblot analysis revealed that the skin cell line medium contained several activin and bone morphogenetic protein moieties. Antibody specific to activin neutralized most of the CGRP-inductive activity in skin conditioned medium. These data indicate that the CGRP-inductive action of skin cells involves activin and establish activin as a candidate regulator of this sensory neuropeptide phenotype during development. PMID- 11203695 TI - Are pioneer axons guided by regulatory gene expression domains in the zebrafish forebrain? High-resolution analysis of the patterning of the zebrafish brain during axon tract formation. AB - Although the principles of axon growth are well understood in vitro the mechanisms guiding axons in vivo are less clear. It has been postulated that growing axons in the vertebrate brain follow borders of neuroepithelial cells expressing specific regulatory genes. In the present study we reexamined this hypothesis by analysing the earliest growing axons in the forebrain of embryonic zebrafish. Confocal laser scanning microscopy was used to determine the spatiotemporal relationship between growing axons and the expression pattern of eight regulatory genes in zebrafish brain. Pioneer axons project either longitudinally or dorsoventrally to establish a scaffold of axon tracts during this developmental period. Each of the regulatory genes was expressed in stereotypical domains and the borders of some were oriented along dorsoventral and longitudinal planes. However, none of these borders clearly defined the trajectories of pioneer axons. In two cases axons coursed in proximity to the borders of shh and pax6, but only for a relatively short portion of their pathway. Only later growing axons were closely apposed to the borders of some gene expression domains. These results suggest that pioneer axons in the embryonic forebrain do not follow continuous pathways defined by the borders of regulatory gene expression domains. PMID- 11203696 TI - The pitx2 homeobox protein is required early for endoderm formation and nodal signaling. . AB - Nodal and Nodal-related factors play fundamental roles in a number of developmental processes, including mesoderm and endoderm formation, patterning of the anterior neural plate, and determination of bilateral asymmetry in vertebrates. pitx2, a paired-like homeobox gene, has been proposed to act downstream of Nodal in the gene cascade providing left-right cues to the developing organs. Here, we report that pitx2 is required early in the Nodal signaling pathway for specification of the endodermal and mesodermal germ layers. We found that pitx2 is expressed very early during Xenopus and zebrafish development and in many regions where Nodal signaling is required, including the presumptive mesoderm and endoderm at the blastula and gastrula stages and the prechordal mesoderm at later stages. In Xenopus embryos, overexpression of pitx2 caused ectopic expression of goosecoid and sox-17 and interfered with mesoderm formation. Overexpression of pitx2 in Xenopus animal cap explants partially mimics the effects of Nodal overexpression, suggesting that pitx2 is a mediator of Nodal signaling during specification of the endoderm and prechordal plate, but not during mesoderm induction. We further demonstrate that pitx2 is induced by Nodal signaling in Xenopus animal caps and that the early expression of zebrafish pitx2 is absent when the Nodal signaling pathway is inactive. Inhibition of pitx2 function using a chimeric EnR-pitx2 blocked specification of the mesoderm and endoderm and caused severe embryonic defects resembling those seen when Nodal signaling is inhibited. Following inhibition of pitx2 function, the fate of ventral vegetal blastomeres was shifted from an endodermal to a more mesodermal fate, an effect that was reversed by wild-type pitx2. Finally, we show that inhibition of pitx2 function interferes with the response of cells to Nodal signaling. Our results provide direct evidence that pitx2 function is required for normal specification of the endodermal and mesodermal germ layers. PMID- 11203698 TI - MyoD cannot compensate for the absence of myogenin during skeletal muscle differentiation in murine embryonic stem cells. AB - myogenin (-/-) mice display severe skeletal muscle defects despite expressing normal levels of MyoD. The failure of MyoD to compensate for myogenin could be explained by distinctions in protein function or by differences in patterns of gene expression. To distinguish between these two possibilities, we compared the abilities of constitutively expressed myogenin and MyoD to support muscle differentiation in embryoid bodies made from myogenin (-/-) ES cells. Differentiated embryoid bodies from wild-type embryonic stem (ES) cells made extensive skeletal muscle, but embryoid bodies from myogenin (-/-) ES cells had greatly attenuated muscle-forming capacity. The inability of myogenin (-/-) ES cells to generate muscle was independent of endogenous MyoD expression. Skeletal muscle was restored in myogenin (-/-) ES cells by constitutive expression of myogenin. In contrast, constitutive expression of MyoD resulted in only marginal enhancement of skeletal muscle, although myocyte numbers greatly increased. The results indicated that constitutive expression of MyoD led to enhanced myogenic commitment of myogenin (-/-) cells but also indicated that committed cells were impaired in their ability to form muscle sheets without myogenin. Thus, despite their relatedness, myogenin's role in muscle formation is distinct from that of MyoD, and the distinction cannot be explained merely by differences in their expression properties. PMID- 11203697 TI - Neurogenin2 expression in ventral and dorsal spinal neural tube progenitor cells is regulated by distinct enhancers. AB - The basic helix-loop-helix transcription factor Neurogenin2 (NGN2) is expressed in distinct populations of neural progenitor cells within the developing central and peripheral nervous systems. Transgenic mice containing ngn2/lacZ reporter constructs were used to study the regulation of ngn2 in the developing spinal cord. ngn2/lacZ transgenic embryos containing sequence found 5' or 3' to the ngn2 coding region express lacZ in domains that reflect the spatial and temporal expression profile of endogenous ngn2. A 4.4-kb fragment 5' of ngn2 was sufficient to drive lacZ expression in the ventral neural tube, whereas a 1.0-kb fragment located 3' of ngn2 directed expression to both dorsal and ventral domains. Persistent -gal activity revealed that the NGN2 progenitor cells in the dorsal domain give rise to a subset of interneurons that send their axons to the floor plate, and the NGN2 progenitors in the ventral domain give rise to a subset of motor neurons. We identified a discrete element that is required for the activity of the ngn2 enhancer specifically in the ventral neural tube. Thus, separable regulatory elements that direct ngn2 expression to distinct neural progenitor populations have been defined. PMID- 11203699 TI - Expression and function of a stem cell promoter for the murine CBFalpha2 gene: distinct roles and regulation in natural killer and T cell development. AB - The Runt family transcription factor CBFalpha2 (AML1, PEBP2alphaB, or Runx1) is required by hematopoietic stem cells and expressed at high levels in T-lineage cells. In human T cells CBFalpha2 is usually transcribed from a different promoter (distal promoter) than in myeloid cells (proximal promoter), but the developmental and functional significance of this promoter switch has not been known. Here, we report that both coding and noncoding sequences of the distal 5' end are highly conserved between the human and the murine genes, and the distal promoter is responsible for the overwhelming majority of CBFalpha2 expression in murine hematopoietic stem cells as well as in T cells. Distal promoter activity is maintained throughout T cell development and at lower levels in B cell development, but downregulated in natural killer cell development. The distal N terminal isoform binds to functionally important regulatory sites from known target genes with two- to threefold higher affinity than the proximal N-terminal isoform. Neither full-length isoform alters growth of a myeloid cell line under nondifferentiating conditions, but the proximal isoform selectively delays mitotic arrest of the cell line under differentiating conditions, resulting in the generation of greater numbers of neutrophils. PMID- 11203700 TI - Gdf11 is a negative regulator of chondrogenesis and myogenesis in the developing chick limb. AB - GDF11, a new member of the TGF-beta gene superfamily, regulates anterior/posterior patterning in the axial skeleton during mouse embryogenesis. Gdf11 null mice display skeletal abnormalities that appear to represent anterior homeotic transformations of vertebrae consistent with high levels of Gdf11 expression in the primitive streak, presomitic mesoderm, and tail bud. However, despite strong Gdf11 expression in the limb throughout development, this structure does not appear to be affected in the knockout mice. In order to understand this dichotomy of Gdf11 expression versus Gdf11 function, we identified the chicken Gdf11 gene and studied its role during limb formation. In the early limb bud, Gdf11 transcripts are detected in the subectodermal mesoderm at the distal tip, in a region overlapping the progress zone. At these stages, Gdf11 is excluded from the central core mesenchyme where precartilaginous condensations will form. Later in development, Gdf11 continues to be expressed in the distal most mesenchyme and can also be detected more proximally, in between the forming skeletal elements. When beads incubated in GDF11 protein were implanted into the early wing bud, GDF11 caused severe truncations of the limb that affected both the cartilage elements and the muscle. Limb shortening appeared to be the result of an inhibition of chondrogenesis and myogenesis and using an in vitro micromass assay, we confirmed the negative effects of GDF11 on both myogenic and chondrogenic cell differentiation. Analysis of molecular markers of skeletal patterning revealed that GDF11 induced ectopic expression of Hoxd-11 and Hoxd-13, but not of Hoxa-11, Hoxa-13, or the Msx genes. These data suggest that GDF11 may be involved in controlling the late distal expression of the Hoxd genes during limb development and that misregulation of these Hox genes by excess GDF11 may cause some of the observed alterations in skeletal element shape. In addition, GDF11 induced the expression of its own antagonist follistatin, indicating that the activity of GFD11 may be limited by a negative feedback mechanism. The data from our studies in the chick suggest that Gdf11 plays a role in the formation and development of the avian limb skeleton. PMID- 11203701 TI - TNF signaling via the ligand-receptor pair ectodysplasin and edar controls the function of epithelial signaling centers and is regulated by Wnt and activin during tooth organogenesis. AB - Ectodermal dysplasia syndromes affect the development of several organs, including hair, teeth, and glands. The recent cloning of two genes responsible for these syndromes has led to the identification of a novel TNF family ligand, ectodysplasin, and TNF receptor, edar. This has indicated a developmental regulatory role for TNFs for the first time. Our in situ hybridization analysis of the expression of ectodysplasin (encoded by the Tabby gene) and edar (encoded by the downless gene) during mouse tooth morphogenesis showed that they are expressed in complementary patterns exclusively in ectodermal tissue layer. Edar was expressed reiteratively in signaling centers regulating key steps in morphogenesis. The analysis of the effects of eight signaling molecules in the TGFbeta, FGF, Hh, Wnt, and EGF families in tooth explant cultures revealed that the expression of edar was induced by activinbetaA, whereas Wnt6 induced ectodysplasin expression. Moreover, ectodysplasin expression was downregulated in branchial arch epithelium and in tooth germs of Lef1 mutant mice, suggesting that signaling by ectodysplasin is regulated by LEF-1-mediated Wnt signals. The analysis of the signaling centers in tooth germs of Tabby mice (ectodysplasin null mutants) indicated that in the absence of ectodysplasin the signaling centers were small. However, no downstream targets of ectodysplasin signaling were identified among several genes expressed in the signaling centers. We conclude that ectodysplasin functions as a planar signal between ectodermal compartments and regulates the function, but not the induction, of epithelial signaling centers. This TNF signaling is tightly associated with epithelial mesenchymal interactions and with other signaling pathways regulating organogenesis. We suggest that activin signaling from mesenchyme induces the expression of the TNF receptor edar in the epithelial signaling centers, thus making them responsive to Wnt-induced ectodysplasin from the nearby ectoderm. This is the first demonstration of integration of the Wnt, activin, and TNF signaling pathways. PMID- 11203702 TI - Functional domains of the LIM homeodomain protein Xlim-1 involved in negative regulation, transactivation, and axis formation in Xenopus embryos. AB - The Xenopus LIM homeodomain protein Xlim-1 is specifically expressed in the Spemann organizer region and assumed to play a role in the establishment of the body axis as a transcriptional activator. To further elucidate the mechanism underlying the regulation of its transcriptional activity, we focused on the region C-terminal to the homeodomain of Xlim-1 (CT239-403) and divided it into five regions, CCR1-5 (C-terminal conserved regions), based on similarity between Xlim-1 and its paralog, Xlim-5. The role of Xlim-1 CT239-403 in the Spemann organizer was analyzed by assaying the axis-forming ability of a series of CCR-mutated constructs in Xenopus embryos. We show that high doses of Xlim-1 constructs deleted of CCR1 or CCR2 initiate secondary axis formation in the absence of its coactivator Ldb1 (LIM-domain-binding protein 1), suggesting that CCR1 and CCR2 are involved in negative regulation of Xlim-1. In contrast, while Xlim-1 is capable of initiating secondary axis formation at low doses in the presence of Ldb1, deletion of CCR2 (aa 275-295) or substitution of five conserved tyrosines in CCR2 with alanines (CCR2-5YA) abolished the activity. In addition, UAS-GAL4 one-hybrid reporter assays in Xenopus showed that CCR2, but not CCR2 5YA, with its flanking regions (aa 261-315) functions as a transactivation domain when fused to the GAL4 DNA-binding domain. Finally, we show that none of the known transcriptional coactivators tested (CBP, SRC-1, and TIF2) interacts with the Xlim-1 transactivation domain (aa 261-315). Thus, Xlim-1 not only contains a unique tyrosine-rich activation domain but also contains a negative regulatory domain in CT239-403, suggesting a complex regulatory mechanism underlying the transcriptional activity of Xlim-1 in the organizer. PMID- 11203703 TI - Autonomous transition into meiosis of mouse fetal germ cells in vitro and its inhibition by gp130-mediated signaling. AB - Mouse primordial germ cells (PGCs) arrive at the urogenital ridge (UGR) at around 10.5 days postcoitum (dpc). They proliferate until around 13.5 dpc, then enter into meiosis in the female or become mitotically arrested in the male gonads. In this study, meiotic transition of mouse PGCs was examined in vitro. Female PGCs obtained from UGRs or genital ridges at 10.5-11.5 dpc began to express meiosis-specific genes, Scp3 and Dmc1, after dissociation and cultivation on feeder cells for several days. Meiotic transition into the leptotene stage was confirmed by the formation of axial cores. Male PGCs at 10.5-11.5 dpc and migratory PGCs obtained from mesenteries at 10.5 dpc also expressed Scp3 and formed axial cores after several days of culture, supporting the hypothesis that PGCs are capable of entering meiosis before arriving at the UGR. gp130 mediated signaling, known to promote survival/growth of PGCs and also to inhibit the differentiation of embryonic stem cells, suppressed the expression of Scp3 in PGCs and inhibited the following formation of axial cores in vitro. This novel activity of gp130-mediated signaling may provide some clues for the understanding of pluripotency of mammalian germ-line cells and/or the sex differentiation of fetal germ cells. PMID- 11203704 TI - The Caenorhabditis elegans peb-1 gene encodes a novel DNA-binding protein involved in morphogenesis of the pharynx, vulva, and hindgut. AB - Gene expression in the Caenorhabditis elegans pharynx is regulated in part by organ-specific signals, which in the myo-2 gene target a regulatory sequence called the C sub-element. C sub-element activity requires the organ specification factor PHA-4, a winged-helix transcription factor expressed in all pharyngeal cells. To identify additional factors involved in pharyngeal organogenesis, we performed a yeast one-hybrid screen for C sub-element binding proteins. Here we describe the novel factor PEB-1, which is coexpressed with PHA-4 in many pharyngeal cell types, including muscles, epithelial cells, marginal cells, and glands, but is undetectable in the pharyngeal nervous system. PEB-1 is also detected outside the pharynx in cells surrounding the rectum and vulva, as well as in the germ line. Reduction of peb-1 function using RNAi results in morphological defects in the somatic tissues in which peb-1 is expressed. We have mapped the PEB-1 DNA-binding domain to a 158-residue region, which is unrelated to known DNA-binding proteins but shares some sequence similarity to the Drosophila Mod(mdg4) proteins. PEB-1 specifically recognizes a site in the C subelement that partially overlaps the PHA-4 binding site. Both the PEB-1 and the PHA-4 binding sites are necessary for strong C sub-element enhancer activity in some cells in which these factors are coexpressed. In contrast the PEB-1 site is dispensable for C sub-element activity in pharyngeal neurons. We propose that PEB 1 functions with PHA-4 to activate target gene expression in cells in which they are coexpressed. PMID- 11203705 TI - Role of caspases and mitochondria in the steroid-induced programmed cell death of a motoneuron during metamorphosis. AB - Accessory planta retractor (APR) motoneurons of the hawk moth, Manduca sexta, undergo a segment-specific pattern of programmed cell death (PCD) 24 to 48 h after pupal ecdysis (PE). Cell culture experiments show that the PCD of APRs in abdominal segment 6 [APR(6)s] is a cell-autonomous response to the steroid hormone 20-hydroxyecdysone (20E) and involves mitochondrial demise and cell shrinkage. Twenty-four hours before PE, at stage W3-noon, APR(6)s require further 20E exposure and protein synthesis (as tested with cycloheximide) to undergo PCD, and death can be blocked by a broad-spectrum caspase inhibitor. By PE, death is 20E- and protein synthesis-independent and the caspase inhibitor blocks cell shrinkage but not loss of mitochondrial function. Thus, the commitment to mitochondrial demise precedes the commitment to execution events. The phenotype of necrotic cell death induced by a mitochondrial electron transfer inhibitor differs unambiguously from 20E-induced PCD. By inducing PCD pharmacologically, the readiness of APR(6)s to execute PCD was found to increase during the final larval instar. These data suggest that the 20E-induced PCD of APR(6)s includes a premitochondrial phase which includes 20E-induced synthetic events and apical caspase activity, a mitochondrial phase which culminates in loss of mitochondrial function, and a postmitochondrial phase during which effector caspases are activated and APR(6) is destroyed. PMID- 11203707 TI - Left sided inferior vena cava with sinus venosus type atrial septal defect. AB - A patient with left sided inferior vena cava and sinus venosus type atrial septal defect is presented. The patient was situs solitus, had abnormal pulmonary venous drainage and the left sided inferior caval vein returned to its usual route after the renal vein junction. PMID- 11203708 TI - Electrocardiographic issues related to action potential phases 1 and 2 on the occasion of a case of accidental mild hypothermia. AB - A 29-year-old man was accidentally exposed to cold and his mild hypothermia uniquely resulted in the transient exaggeration of his normothermic electrocardiographic findings, which were consistent with early repolarization. A unifying concept of clinical entities with similar J wave and ST segment elevation (J-ST syndrome) is proposed. PMID- 11203709 TI - Variant angina with a strong spasmodic trait. AB - A 55-year-old man came to the hospital because of chest pain, mostly occurring in the early morning at rest. He had to get isosorbide dinitrate intravenously with continuous infusion. Following ergonovine provocation test, total occlusion of mid-left anterior descending artery was identified with marked elevation of ST segment as exercise test showed despite isosorbide dinitrate. PMID- 11203710 TI - Aneurysm of sinus of Valsalva with extensive dissection of interventricular septum and left ventricular free wall. PMID- 11203711 TI - Early coronary disease in diabetic male patients. PMID- 11203712 TI - Unruptured left ventricular pseudoaneurysm. PMID- 11203714 TI - Effects of video information on pre-colonoscopy anxiety and knowledge: a randomized trial. PMID- 11203713 TI - Postal consent for upper gastrointestinal endoscopy. PMID- 11203715 TI - Focus on... Christian Albert Theodor Billroth (1829-1894). PMID- 11203716 TI - Differences in umbilical venous and arterial leptin levels by mode of delivery. PMID- 11203717 TI - Primary psoa abscess. PMID- 11203718 TI - Klippel-Feil syndrome in the prehispanic population of El Hierro (Canary Islands). PMID- 11203719 TI - Haematopoietic stem cell transplantation (HSCT) in a patient with Sjogren's syndrome and lung malt lymphoma cured lymphoma not the autoimmune disease. PMID- 11203720 TI - Castleman's disease. PMID- 11203721 TI - Intranasal midazolam for treating febrile seizures in children. Buccal midazolam for childhood seizures at home preferred to rectal diazepam. PMID- 11203723 TI - Training overseas doctors in the United Kingdom. We need to debunk the myth about training. . PMID- 11203724 TI - Training overseas doctors in the United Kingdom. Consider moving to the US. PMID- 11203725 TI - Training overseas doctors in the United Kingdom. Frequency of PLAB tests should match available jobs. PMID- 11203726 TI - Orlistat associated with hypertension. Roche concludes that there is not evidence of a casual association. PMID- 11203727 TI - Orlistat associated with hypertension. Digit preference lays conclusions about orlistat open to doubt. PMID- 11203728 TI - Familial hypercholesterolaemia is underdiagnosed after AMI. PMID- 11203729 TI - Psychiatric disorders and risky sexual behaviour. Paper did not mention sexual orientation. PMID- 11203730 TI - Psychiatric disorders and risky sexual behavior. Risky sexual behaviour is part of two disorders examined. . PMID- 11203731 TI - Screening for medium chain acyl-CoA dehydrogenase deficiency has still not been evaluated. . PMID- 11203732 TI - Cholera sweeps through South African province. . PMID- 11203733 TI - "Health weather forecasts" to be piloted in England. . PMID- 11203734 TI - Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids of patients with temporomandibular joint osteoarthritis. AB - AIMS: Imbalance between matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) may be involved in the breakdown of articular cartilage matrix of the temporomandibular joint (TMJ). In this study, MMPs, TIMPs, and MMP-1/TIMP-1 complex levels were examined in TMJ synovial fluid samples aspirated from TMJ osteoarthritis (OA) patients (2 males, 8 females; mean age, 29.7 years) and asymptomatic control subjects (2 males, 8 females; mean age, 23.6 years) to determine the likelihood of increased proteolytic activity in the OA joints. METHODS: The various types of MMPs and TIMPs were detected by Western blotting with monoclonal antibodies and gelatin zymography. The MMP-1/TIMP-1 complex level was measured by an enzyme-linked immunosorbent assay kit. All aspirates were first analyzed for total protein content and then individually diluted to make the total protein levels equivalent. RESULTS: The mean MMP-1/TIMP-1 complex concentration in the synovial fluids of the OA patients was 3.92 +/- 1.39 ng/mL; this value was significantly lower (P < 0.05) than the value from control subjects (5.46 +/- 1.32 ng/mL). Matrix metalloproteinase-1 (52 kDa), MMP-3 (57 kDa), TIMP-1 (28 kDa), and TIMP-2 (26 kDa) were detected in all of the normal and the OA samples. However, MMP-1 (28 kDa), MMP-2 (72 kDa), MMP-3 (45 kDa), and MMP 9 (83 kDa) were detected in higher concentration in the OA samples. CONCLUSION: These findings suggest a strong association between the OA-active joints and the presence of biologically active forms of known tissue degradation enzymes (MMP-1, MMP-3, and MMP-9). PMID- 11203735 TI - Topical application of capsaicin for the treatment of localized pain in the temporomandibular joint area. AB - AIMS: To determine the effectiveness of topical capsaicin cream application on localized pain in the temporomandibular joint (TMJ) area. METHODS: A randomized, double-blind, placebo-controlled study was conducted on 30 patients suffering from unilateral pain in the TMJ area. Patients were randomly divided into experimental and placebo groups; they were instructed to apply 0.025% capsaicin cream or its vehicle to the painful TMJ area 4 times daily for 4 weeks. Subjective parameters of present pain, most severe pain, effect of pain on daily activities, and pain relief were assessed each week on a visual analog scale. Muscle and joint sensitivity to palpation on the painful and contralateral joints and maximal mouth opening (assisted/passive and non-assisted/active) were examined weekly by the same experienced examiner. RESULTS: Capsaicin cream produced no statistically significant influence on measured variables when compared to placebo. Both experimental and placebo groups showed statistically significant improvement in most variables during the experiment. CONCLUSION: The factor of time had a major effect in the non-specific improvement of the parameters assessed. The placebo effect played an important role in the treatment of patients with pain in the TMJ area. PMID- 11203736 TI - Plasma and serum serotonin levels and their relationship to orofacial pain and anxiety in fibromyalgia. AB - AIMS: Serum serotonin levels (S-5-HT) have been reported to be reduced in patients with fibromyalgia and to show a negative correlation with pain. We hypothesized that one mechanism behind this could be that platelets are activated to release 5-HT into the plasma compartment (P-5-HT), which then binds to nociceptors. The aims of this study were therefore to investigate the relation between P-5-HT and S-5-HT and their relationship versus orofacial pain and anxiety in fibromyalgia. METHODS: Twelve patients with fibromyalgia, 12 patients with rheumatoid arthritis, and 12 healthy individuals participated in the study. Pain measures used were pain intensity assessed with a visual analog scale, pain drawings, and influence of pain on daily living activities (ADL). The Spielberger State and Trait Anxiety Inventory (STAI) scale was used for self-rating of anxiety levels. The participants were examined clinically, and the pressure pain threshold (PPT) over the masseter muscle was assessed. Finally, venous blood was collected for analysis of P-5-HT and S-5-HT. RESULTS: The ratio between P-5-HT and S-5-HT was calculated to determine the relative plasma fraction of serotonin (RPS). Patients with fibromyalgia showed significantly lower S-5-HT than did patients with rheumatoid arthritis. They also showed significantly higher STAI scores and tender point index of orofacial muscles and significantly lower PPT than the healthy individuals. High RPS was associated with high ADL and STAI scores. CONCLUSION: This study indicates that a high level of plasma serotonin in relation to serum level is associated with pain discomfort and increased anxiety in fibromyalgia. PMID- 11203738 TI - Orofacial pain: quo vadis? PMID- 11203737 TI - Generic pain intensity scores are affected by painful comorbidity. AB - AIMS: To determine the degree to which the generic pain intensity rating (i.e., overall and without reference to a particular body site) of facial pain patients being seen in a specialty setting for facial pain is influenced by painful comorbidity in body parts other than the face. METHODS: In this prospective study, 40 consecutive female temporomandibular pain patients rated their generic pain on a 100-mm visual analog scale. After marking all painful body sites on pain drawings, patients were asked to rate the pain intensity for each of the indicated pain sites; the patients did not have access to the generic pain intensity score. Pearson's correlation coefficient was used to correlate the generic pain intensity score with site-specific pain intensity ratings, their mean and maximum, and the number of pain sites. RESULTS: The medians of the generic, maximum, and facial pain intensity scores were 49.5, 53, and 45.5, respectively. The generic pain intensity rating correlated more highly with the intensity scores reported for the most painful body site (r2 = 0.82; P < 0.001) than with the average rating across all painful sites (r2 = 0.62; P < 0.001), or the pain intensity score in the face (r2 = 0.61; P < 0.001). The number of pain sites did not correlate to any statistically significant degree with the generic pain intensity rating (r2 = 0.006; P = 0.65). CONCLUSION: The results of this study suggest that the maximum visual analog scale pain intensity score, observed in any body location, is a better reflection of the generic pain intensity rating than the corresponding score of the face. To avoid over-rating or underrating of facial pain intensity, patients should be instructed to provide site-specific pain intensity scores if painful comorbidity is present. PMID- 11203739 TI - Personality characteristics and accompanying symptoms in temporomandibular joint dysfunction, headache, and facial pain. AB - AIMS: Patients with different facial pain/headache pathologies usually complain of numerous accompanying symptoms relative to systemic dysfunctions or to the patient's personality characteristics. The purpose of this work was: (1) to determine the prevalence of accompanying symptoms in groups of patients with temporomandibular joint (TMJ) dysfunction and other types of facial pain or headache disorders, (2) to assess the patients' personality characteristics and anxiety levels, and (3) to see whether significant differences were found between the groups. METHODS: Two hundred forty-three patients were considered. They had TMJ intracapsular disorder (TMJ, n = 71), tension-type headache (TH, n = 52), migraine (M, n = 68), chronic daily headache (CDH, n = 26), or facial pain disorder as somatoform disorder (FP, n = 26). The presence of 23 symptoms was assessed; the Minnesota Multiphasic Personality Inventory (MMPI) and the Spielberger State and Trait Anxiety Inventory (STAI) were administered and the relative scores were calculated. Four different MMPI clusters (depressive, conversive, emotional, coper) were also considered. Intergroup differences were assessed by Chi-square analysis, 1-way analysis of variance, Bonferroni t test, and a logistic regression model and then standardized for gender and age, taking the tension-type headache group as a common reference group. RESULTS: The TMJ group had: (1) a lower prevalence of almost all symptoms; (2) significantly lower scores of several MMPI and of state anxiety; and (3) odds ratio values < 1 for all symptoms except phobias and for emotional, conversive, and depressive MMPI profiles. The FP and CDH groups had the highest prevalence of the majority of symptoms and higher MMPI and STAI scale elevations. CONCLUSION: It is concluded that some types of headache and facial pain seem to correlate with the presence of a number of accompanying symptoms and with some changes in personality. These changes are particularly relevant in patients with chronic daily headache and facial pain disorder. In contrast, patients with TMJ intracapsular disorders tended to show a low prevalence of accompanying symptoms and a normal personality profile. PMID- 11203740 TI - Psychosocial profiles of patients with burning mouth syndrome. AB - AIMS: Burning mouth syndrome (BMS) is estimated to affect 1 to 5% of the adult population, with women experiencing symptoms more frequently than men. The purpose of this study was to examine the psychosocial profiles of BMS patients to determine whether psychologic factors are related to pain reports. Based on previous literature, it was hypothesized that patients with BMS would be characterized by clinical elevations on standardized psychologic assessment instruments that included the Revised Symptom Checklist (SCL-90R) and the Multidimensional Pain Inventory (MPI). METHODS: Thirty-three BMS patients completed the McGill Pain Questionnaire, MPI, and SCL-90R during their initial clinical evaluation session. The SCL-90R and MPI data were then summarized and presented in standardized format (T-scores) to enable meaningful comparisons with larger population samples that included both a chronic pain population and a normal nonclinical sample. RESULTS: The T-score for the overall pain severity on the MPI was 40.8 (SD 12.8). For the entire BMS sample, there was no evidence for significant clinical elevations on any of the SCL-90R subscales, including depression, anxiety, and somatization. Moreover, patients reported significantly fewer disruptions in normal activities as a result of their oral burning pain than did a large sample of chronic pain patients. CONCLUSION: These findings indicate that, as a group, this sample of BMS patients did not report significant psychologic distress. There were, however, individual cases (7 of 33, or 21%) where psychometric data indicated a likelihood of psychologic distress, and further evaluation by a competent health professional would be warranted for those individuals. PMID- 11203741 TI - Dynamic magnetic resonance imaging technique for the study of the temporomandibular joint. AB - AIMS: Echo planar imaging (EPI) is an ultrafast magnetic resonance imaging (MRI) technique that can scan a single frame in less than a second. The aim of this study was to use the EPI technique to develop a new dynamic MRI protocol for the temporomandibular joint (TMJ). METHODS: Basic fast-field echo and EPI pulse sequences were used for dynamic studies of the TMJ. The subjects were instructed to perform spontaneous, continuous, slow opening/closing movements without visual or audio feedback. Different scanning parameter settings were explored to optimize the results. RESULTS: With an opening/closing movement of approximately 6 to 7 seconds per cycle, the proposed protocol yielded a good insight into the relative motion between condyle and disc. It was also possible to see the deformation of the disc during movement. CONCLUSION: The EPI technique is a non invasive technique that can be used for dynamic imaging study of a slow but continuous, uninterrupted jaw movement. PMID- 11203742 TI - Ninth World Congress International Association for the Study of Pain. August 22 27, 1999 Vienna, Austria. PMID- 11203743 TI - The efficacy of potassium salts as agents for treating dentin hypersensitivity. AB - Formulations containing potassium salts (e.g., chloride, nitrate, citrate, oxalate) are widely used for treating dentin hypersensitivity (DH). The purpose of this review was to evaluate evidence for the clinical efficacy of potassium salts in reducing DH and also to consider the biologic basis for any effects. Literature searches were used to identify reports of clinical trials of potassium containing preparations. Searches revealed 3 trials of potassium nitrate solutions or gels; 2 trials of mouthwashes containing potassium nitrate or citrate; 6 trials of potassium oxalates; and 16 double-blind randomized trials of toothpastes containing potassium nitrate, chloride, or citrate. The toothpaste studies provided quantitative data on treatment effects. These outcome measures were expressed as percentage reductions in sensitivity to cold air and mechanical stimulation and the patients' subjective reports. Trials of topically applied solutions yielded inconsistent results. Potassium-containing mouthwashes produced significant reductions in sensitivity. All potassium-containing toothpastes produced a significant reduction in sensitivity to tactile and air stimuli, as well as subjectively reported sensitivity. In most studies, the active agent (potassium) was superior to the minus-active control (placebo), but a few of the more recent trials have demonstrated significant placebo effects. It is postulated that potassium ions released from toothpastes diffuse along the dentinal tubules to inactivate intradental nerves. However, this principle has never been confirmed in intact human teeth. The mechanism of the desensitizing effects of potassium-containing toothpastes remains uncertain at present. PMID- 11203744 TI - Does the ovarian cycle influence the pressure-pain threshold of the masticatory muscles in symptom-free women? AB - AIMS: To test the hypothesis that the ovarian cycle influences the pressure-pain threshold of the masticatory muscles. METHODS: Eighteen healthy women with a regular menstrual cycle (28 +/- 2 days), ranging in age from 18 to 35 years, participated in the study. For each subject, pressure-pain thresholds (PPTs) of the masseter and temporalis muscles were assessed at 4 muscular sites by means of an electronic algometer. Measurements were taken at 4 separate sessions across the menstrual cycle corresponding to the following phases: menstrual, follicular, periovulatory, and luteal. Menstrual cycle phases were determined by a pelvic ultrasonographic screening. The study was carried out in a single-blind design, and the initial session was randomly determined for each individual. Data collected were analyzed by repeated-measures analysis of variance. RESULTS: The findings suggest that the PPTs of several masticatory muscles (2 of 4) are influenced by the ovarian cycle, but to a minor extent (P < 0.05), and the influence is of limited clinical relevance. CONCLUSION: In healthy subjects, there is a link between mechanical sensitivity of the masticatory muscles and fluctuation of the ovarian hormones. The relationship between PPTs of the masticatory muscles and the ovarian cycle should be also investigated in patients with temporomandibular disorders and/or orofacial pain conditions. PMID- 11203745 TI - Somatic, affective, and pain characteristics of chronic TMD patients with sexual versus physical abuse histories. AB - AIMS: This study examined whether temporomandibular disorder (TMD) patients with sexual versus physical abuse histories differ in their pain report, psychological distress, and somatic symptoms. METHODS: Participants were 114 female TMD patients. The sample was divided into 3 groups based on abuse history: sexual abuse, physical abuse, or no abuse. Abuse histories were assessed with a structured clinical interview. Measures used included the McGill Pain Questionnaire, the State-Trait Anxiety Inventory, the Beck Depression Inventory, and the Pennebaker Inventory of Limbic Languidness. Group differences were analyzed by analysis of variance and Bonferroni post hoc comparisons. RESULTS: Temporomandibular disorder patients with a history of physical abuse reported significantly more pain, anxiety, and depressive symptoms than did patients with a history of sexual abuse or no history of abuse. Furthermore, the results suggest that TMD patients with a sexual abuse history are not significantly different from patients with no abuse history across the domains studied. CONCLUSION: Based on the differences found, it can be argued that assessment of physical abuse histories by appropriately trained clinicians should be a routine part of any multimodal assessment of female chronic TMD patients. PMID- 11203746 TI - Influence of biased clinician statements on patient report of referred pain. AB - AIMS: The purpose of this study was to examine the influence of clinician bias on patients' reports of referred pain. Diagnosis of temporomandibular disorders is dependent on subjective reports of pain and referred pain upon manual muscle palpation. The influence of biased clinician statements in such subjective reports has not been previously investigated. METHODS: Forty subjects with pain and who met specific inclusion criteria were randomly assigned to 1 of 2 experimental groups. One group was subjected to a standardized biasing statement, while the other group was not. Tender points in the masseter muscle were then stimulated with a pressure algometer to the pressure-pain threshold. Subjects then recorded the presence or absence, location, intensity, and unpleasantness of any referred pain. State-trait anxiety and social desirability were also assessed to explore the possibility that anxiety levels or subjects' desires to please the experimenter influenced results. RESULTS: The biased group reported increased presence (P < 0.01), intensity (P < 0.001), and unpleasantness (P < 0.003) of referred pain as compared to the non-biased group. There were no differences between groups on state-trait anxiety or social desirability (P > 0.05). CONCLUSION: These data suggest that patient reports of pain referral may be subject to clinician bias, and recommendations to control this bias are offered. PMID- 11203747 TI - Individualized oblique-axial magnetic resonance imaging for improved visualization of mediolateral TMJ disc displacement. AB - AIMS: A new individualized oblique-axial orientation of magnetic resonance imaging scans of the temporomandibular joint (TMJ), corrected to be perpendicular to the tangent of the posterior slope of the articular eminence, has been proposed to improve the representation of the disc. The aim of this study was to evaluate the quality of the images obtained with this new type of scanning plane and to assess the factors that can affect the scans. METHODS: Twenty-nine TMJs were scanned by the use of sagittal, conventional coronal, and individualized oblique-axial scanning planes. On the sagittal images, the angle alpha between the tangent of the posterior slope of the articular eminence and the vertical was measured, and the disc position was evaluated. For both imaging planes, 2 examiners, blind to the scanning techniques, counted the number of conventional coronal and oblique-axial scans in which the disc was visible and in which the medial and lateral disc borders were well demarcated and evaluated the mediolateral disc position. RESULTS: The individualized oblique-axial technique was superior to the conventional coronal technique in depicting the disc and its medial and lateral demarcations (paired t test, P < 0.05). The possibility of correct diagnosis of the mediolateral disc position and the agreement between the observers in this evaluation were better with the oblique-axial technique than with the conventional technique (P < 0.05). This was particularly evident when the disc was anteriorly displaced. CONCLUSION: The individualized oblique-axial scanning planes should be used for a better representation of the disc/condyle complex mediolaterally if the disc is anteriorly displaced. PMID- 11203748 TI - Malignancy of the parotid gland with primary symptoms of a temporomandibular disorder. AB - The purpose of this case report is to highlight the possibility that malignant neoplasms of the deep lobe of the parotid gland may present as a temporomandibular disorder (TMD). Two patients who were eventually diagnosed with deep-lobe parotid tumors were retrospectively analyzed clinically, radiographically, and pathologically. For the first patient, there was a prolonged delay in establishing the correct diagnosis; for the second patient the delay was shorter. This was done primarily by computed tomographic examination. Despite aggressive surgical, radiotherapeutic, and chemotherapeutic treatment, both patients died from their malignant disease. All clinicians who treat TMD must be aware of the rare possibility of deep-lobe parotid tumors presenting as a TMD. PMID- 11203749 TI - Trigeminal neuralgia due to an acoustic neuroma in the cerebellopontine angle. AB - This case report first reviews the intracranial tumors associated with symptoms of trigeminal neuralgia (TN). Among patients with TN-like symptoms, 6 to 16% are variously reported to have intracranial tumors. The most common cerebellopontine angle (CPA) tumor to cause TN-like symptoms is a benign tumor called an acoustic neuroma. The reported clinical symptoms of the acoustic neuroma are hearing deficits (60 to 97%), tinnitus (50 to 66%), vestibular disturbances (46 to 59%), numbness or tingling in the face (33%), headache (19 to 29%), dizziness (23%), facial paresis (17%), and trigeminal nerve disturbances (hypesthesia, paresthesia, and neuralgia) (12 to 45%). Magnetic resonance imaging with gadolinium enhancement or computed tomography with contrast media are each reported to have excellent abilities to detect intracranial tumors (92 to 93%). This article then reports a rare case of a young female patient who was mistakenly diagnosed and treated for a temporomandibular disorder but was subsequently found to have an acoustic neuroma located in the CPA. PMID- 11203750 TI - The way forward. PMID- 11203751 TI - Pressure-pain threshold in the human tongue. AB - AIMS: A new pressure algometer was used to quantify the pressure-pain threshold (PPT) in the human tongue. METHODS: A custom-made device controlled by software and a personal computer was used to measure the PPT in the anterior part of the tongues of 14 young, healthy subjects. The PPT was measured at 3 different rates of pressure application on 3 occasions, 1 week apart. Data were evaluated with analysis of covariance and intraclass correlations. RESULTS: The prototype device had linear output characteristics within the operational range. The mean PPT ranged from 18 to 44 g. The PPT appeared to increase approximately linearly with increasing rate of pressure application (P < 0.001). There were no significant differences in the PPT on different experimental occasions. In individual subjects, the PPT was reliable and uniform. There were significant inter-subject differences in the PPT (P < 0.001). CONCLUSION: The PPT can be measured consistently in the anterior part of the tongue, provided the pressure rate is controlled. The new-pressure algometer appears to have potential clinical utility for quantifying sensation in the human tongue. PMID- 11203752 TI - Absolute and relative facial pressure-pain thresholds in healthy individuals. AB - AIMS: To investigate and compare absolute pressure-pain threshold (PPT) levels and ratios between craniofacial test and reference sites during consecutive PPT recordings, as well as over a 6-month period, in healthy individuals. This study also investigated PPT differences between genders and the clinical usefulness of different reference sites in the craniofacial region. METHODS: Twelve female and 12 male healthy individuals participated in the first examination. Six months later, 9 females and all of the males returned for a second examination. An electronic algometer was used to make 5 consecutive recordings of PPTs with a 2 minute interval at 3 reference sites: mental protuberance (PRO), first metacarpal bone (MET), and frontal bone (FRO), as well as at 3 test sites: temporomandibular joint, masseter muscle, and temporalis muscle. RESULTS: Absolute PPTs decreased significantly for all test sites during the 5 recordings, while they increased significantly between the examinations. No ratio with FRO as a reference site changed significantly. The males had significantly higher absolute PPTs than the females at PRO and FRO sites. CONCLUSION: This study shows that absolute PPT levels in healthy individuals change significantly during consecutive PPT recordings, as well as over a 6-month period; this limits the usefulness of such measurements. This study also shows that the use of relative PPTs with the FRO as a reference site is useful, both for comparison between groups and for longitudinal studies. PMID- 11203753 TI - Sex, gender, and pain. PMID- 11203754 TI - Gender differences in pain. AB - A review of the literature on gender and clinical pain reveals a disproportionate representation of women receiving treatment for many pain conditions and suggests that women report more severe pain, more frequent pain, and pain of longer duration than do men. Gender differences in pain perception have also been extensively studied in the laboratory, and ratings of experimentally induced pain also show some sex disparity, with females generally reporting lower pain thresholds and tolerance than males. However, there is little consensus on whether these apparent differences reflect the way men and women respond to pain, differing social rules for the expression of pain, or biologic differences in the way noxious stimuli are processed. In this paper, our working hypothesis is that the higher prevalence of chronic orofacial pain in women is a result of sex differences in generic pain mechanisms and of as-yet unidentified factors unique to the craniofacial system. We will review the evidence concerning gender differences in the prevalence of pain conditions, with a focus on orofacial pain conditions. Evidence and hypotheses concerning biologic and psychosocial factors that could influence prevalence rates will also be discussed. PMID- 11203755 TI - A unified concept of idiopathic orofacial pain: pathophysiologic features. AB - Atypical facial pain, stomatodynia, atypical odontalgia, and some forms of masticatory muscle and temporomandibular joint disorders all seem to belong to the same group of idiopathic orofacial pain illnesses. The many common clinical features they display have been discussed in a preceding paper. Some of their common pathophysiologic mechanisms are reviewed in this article. The role of female hormones is suggested as a risk factor by the strong female prevalence and by the effects of physiologic and therapeutic modification of estrogen levels in patients with these pain conditions. Osteoporosis, which appears with menopause, and neuralgia-inducing cavitational osteonecrosis have been linked to atypical facial pain. Similar clinical features have also prompted a comparison between atypical facial pain and complex regional pain syndrome of the limbs. The presence of psychosocial factors is also a common feature, but it is not known whether these are causal or whether the pain induces the psychosocial problem. Local inflammatory, infectious, or mechanical irritation as well as minor nerve trauma are frequently reported in these conditions and can also be considered as risk factors. However, none of the above factors can currently be considered as the sole etiologic factor, and instead the following hypothesis is proposed: the idiopathic pain entities depend on one or several neuropathic mechanisms, the development of which is triggered or favored by one or several events or risk factors. Different neuropathic mechanisms may be at work: nociceptor sensitization, phenotypic changes and ectopic activity from the nociceptors, central sensitization possibly maintained by ongoing activity from initially damaged peripheral tissues, sympathetic abnormal activity, alteration of segmental inhibitory control, and hyper- or hypoactivity of descending controls. Research directions that are suggested include epidemiologic approaches to improve the clinical definition of these conditions, studies to test for the factors and mechanisms proposed, and definition of mechanism-based diagnostic and treatment strategies. PMID- 11203756 TI - Capsaicin-induced muscle hyperalgesia in the exercised and non-exercised human masseter muscle. AB - AIMS: Strong jaw muscle exercises such as tooth grinding in sleep bruxism are frequently believed to be a predisposing factor in myogenous types of temporomandibular disorders. However, it is not known whether tooth grinding in sleep bruxism is associated with increased sensitivity to intramuscular stimuli. This study therefore compared the hyperalgesic effects of an intramuscular injection of capsaicin into the right masseter with and without a prior experimental tooth-grinding exercise. METHODS: Ten healthy men participated in 2 randomized sessions (exercise, non-exercise session) separated by 1 week. In the exercise session, 0.1 mL capsaicin (100 micrograms/mL) was injected into the right masseter immediately after 45 minutes of experimental tooth grinding. In the non-exercise session, the exact same paradigm was used, except that the experimental tooth grinding was omitted. The perceived intensity of pain evoked by intramuscular capsaicin was scored on a 100-mm visual analog scale (VAS). Pain detection thresholds (PDTs) to pressure stimuli and maximal voluntary occlusal force (MVOF) were measured before capsaicin injection; 5, 15, and 45 minutes after the injection; and once a day for the following 3 days. RESULTS: Injections of capsaicin into an exercised or non-exercised masseter did not cause significant differences in peak pain intensity on the VAS (57 +/- 6 mm in exercised masseter vs. 53 +/- 6 mm in non-exercised masseter; P = 0.464). The PDTs in the exercised masseter were significantly decreased for up to 1 day after the capsaicin injection (P < or = 0.038), whereas PDTs in the non-exercised masseter were decreased for only 5 minutes (P = 0.017). The MVOF on the right side was decreased 5 minutes after the capsaicin injection in both sessions (P < 0.010). The MVOF on the left side was significantly reduced for up to 15 minutes after the capsaicin injection in the exercise session only (P < 0.019). CONCLUSION: Increased sensitivity to percutaneous pressure stimuli probably reflects a post-exercise muscle soreness following tooth grinding, whereas intramuscular sensitivity to noxious chemical stimuli immediately following exercise seems to be unchanged. PMID- 11203757 TI - Four-year longitudinal course of TMD symptoms in an adult population and the estimation of risk factors in relation to symptoms. AB - AIMS: To investigate the natural course of symptoms of temporomandibular disorders (TMD) in a non-patient population and to estimate the strength of the relationship between several hypothesized risk factors and precipitation and perpetuation of the symptoms. METHODS: A total of 672 randomly selected citizens of Okayama City was requested to answer the same self-administered questionnaire that they had answered 4 years earlier. The mailed questionnaire failed to reach 58 subjects at the second survey, and 367 of the remaining subjects (59.8%) responded. The fluctuation of TMD symptoms was assessed by comparison of 6 pairs of answers for questions regarding temporomandibular joint (TMJ) pain, limitation of mouth opening, TMJ noise, headache, neck pain, and shoulder stiffness. Six factors (age under 40, female, clenching habit, history of extrinsic trauma, sleep disturbance, and family history of TMD) were tested for their relative risk in precipitating and perpetuating each TMD symptom by the use of its confidence interval to define significance. RESULTS: The incidence of TMD symptoms ranged from 6.1% (TMJ pain) to 12.9% (TMJ noise). More than half of the subjects who had reported TMJ and neck pain at the initial survey no longer reported these symptoms at the second survey, whereas TMJ noise and shoulder stiffness remained in more than 70% of the subjects. Individuals under 40 years old had a 3.3:1 increased risk of precipitating TMJ noise (P < 0.01), individuals with a history of extrinsic trauma had a 2.85:1 increased risk of precipitating limited mouth opening (P < 0.01), and females had a 2.81:1 increased risk of perpetuating TMJ pain (P < 0.01). CONCLUSION: The possible etiologic significance of these factors in TMD should be validated by future research. PMID- 11203758 TI - The International Congress on Orofacial Pain and Temporomandibular Disorders, May 13-14, 2000, Seoul, South Korea. PMID- 11203759 TI - Facing the World Wide Web. PMID- 11203760 TI - Masticatory strains on osseous and ligamentous components of the temporomandibular joint in miniature pigs. AB - AIMS: An animal study of functional biomechanics was undertaken to understand normal loading of the temporomandibular joint (TMJ) and to provide insight into the pathogenesis of TMJ disorders. METHODS: Bone strain and ligamentous deformation were measured during mastication in 26 10-month-old minipigs. Half the subjects had undergone a surgical disruption of the left lateral capsular and disc attachments to the condyle 5 to 6 weeks previously. Rosette strain gauges were bonded to the left lateral surfaces of the squamosal bone near the TMJ, the condylar neck, and the mandibular corpus below the molar region. Differential variable reluctance transducers (DVRTs) were placed bilaterally in the lateral capsular tissue of the joints. Bone strains, ligamentous deformations, and the electromyographic activities of the masseters and lateral pterygoids were recorded during natural mastication. RESULTS: In all animals on both working and balancing sides, mastication caused bone strains that were dominated by tension in the squamosal bone site and by compression in the other sites. Measurements from the DVRT revealed elongation of the lateral capsular tissue in the last phase of the power stroke and shortening in the initial phase of opening, which was almost simultaneous with the development of bone strain. Strain in the capsule ranged from 3 to 25%, with the strain of the balancing side exceeding that of the working side. The surgical disruption did not alter chewing side preference or bone strain, but a tendency toward more extensive ligamentous deformation on the intact side was observed. Furthermore, the ratio of masseter to lateral pterygoid activity was smaller on the disrupted side and larger on the intact side, in comparison to control pigs. CONCLUSION: Both osseous and ligamentous components of the TMJ are strained during mastication, and the latter are more deformed on the balancing side. Disruption of the lateral attachment had little effect on strain in the osseous components but appeared to increase strain in the capsule and to modify the balance of masticatory muscle activity. PMID- 11203761 TI - Changes in pressure-pain thresholds of the jaw muscles during a natural stressful condition in a group of symptom-free subjects. AB - AIMS: To investigate the effects of a natural emotional stressor on pressure-pain thresholds (PPTs) of the masticatory muscles of symptom-free subjects. METHODS: Sixteen healthy dental students were selected before they undertook an academic examination. Sixteen gender-matched students who were not exposed to an examination served as controls. The 2 groups of students were monitored in parallel on 5 separate days over a 1-month period: 2 days before the examination (T1), on the day of the examination (T2), 2 days after (T3), 1 month after (T4), and again after another 2 days (T5). On the day of the examination (T2), the control students were only required to complete a brief, non-demanding questionnaire. On each day, the following parameters were assessed: PPTs of the masseter, the anterior temporalis, and the Achilles tendon; state anxiety; and present stress (measured on a visual analog scale [VAS]). Furthermore, in the students undergoing the examination, venous blood samples for assessment of beta endorphin levels were obtained at T2 and T5. RESULTS: In the stressed students, the PPTs of the masticatory muscles and the Achilles tendon were significantly lower (analysis of variance [ANOVA], P < or = 0.02) on the day of the examination (T2) and on the days nearest the exam (T1, T3), and state anxiety and present stress were significantly higher (ANOVA, P < or = 0.003). No significant change was found in beta-endorphin plasma levels (P > 0.05). In the control group, PPTs, state anxiety, and present stress did not change significantly (ANOVA, P > 0.05). CONCLUSION: The results support a relationship between psychologic stress and pressure-pain sensitivity of the masticatory muscles. PMID- 11203762 TI - Reliability and characteristics of current perception thresholds in the territory of the infraorbital and inferior alveolar nerves. AB - AIMS: To estimate the intra- and interrater reliability of current perception threshold (CPT) evaluation, especially within the infraorbital nerve territory (ION) and inferior alveolar nerve territory (IAN) of the orofacial region, and to characterize the CPTs of ION and IAN in the normal population. METHODS: Electrical stimulation (at 2,000 Hz, 250 Hz, and 5 Hz) was applied to ION and IAN to allow for CPT evaluation in 200 subjects, all of whom were healthy, had no systemic diseases, and were free from symptoms and history of neuropathic conditions. Twenty-five of the subjects were evaluated 3 times by 2 examiners to test reliability, and the remaining subjects were evaluated once for normative data. RESULTS: The intraclass correlation coefficient of CPTs within examiner and between examiners ranged from 0.46 to 0.95. There were no significant differences between right and left sides in CPT evaluation within the ION and IAN territory. Gender and age did not affect the CPT values for ION and IAN in the normal population. There were significant differences between each of the 3 frequency dependent (2,000 Hz, 250 Hz, 5 Hz) measures within ION and IAN (P < 0.001). CONCLUSION: Evaluation of CPTs within ION and IAN revealed good intra- and interrater reliability. The study also provided normative data of CPTs of ION, IAN, and the between-site and within-site ratios of CPTs of ION and IAN. This should prove useful in the diagnosis of orofacial neuropathy. PMID- 11203763 TI - Reproducibility of temporomandibular joint clicking. AB - AIMS: To investigate the stability of temporomandibular joint (TMJ) clicking over a 10-day period and the effect of different open/close velocities on sound amplitude and power spectra in a group of subjects with subjectively stable unilateral clicking during the 3 months preceding the recordings. METHODS: Ten volunteers were recorded with a self-developed microcomputer-based system used in a previous study on asymptomatic subjects. The recordings were performed during 4 different sessions at 3 different open/close rates in each session. The subjective sound intensity was measured with a 100-mm visual analog scale (VAS). The VAS scores, the maximum amplitudes, and the power spectra of the signals were tested for statistical differences among the different open/close rates and over the sessions. The reliability of measurements was also calculated. RESULTS: The maximum amplitude and the power spectra of the TMJ clicking varied between subjects in a broad range that differed from those reported for asymptomatic subjects. No statistically significant differences were found within subjects for the subjective VAS scores for the maximum signal amplitudes or for the power spectrum parameters among the open/close rates and over the 4 sessions. For all 3 open/close rates and for the 4 sessions, a good to excellent reliability of measurements was determined, the values of r being mostly over 0.75. CONCLUSION: Within the limits of the experiment, TMJ clicking was subjectively and objectively stable over a period of 10 days. Therefore, the constant subjective perception of sound intensity was supported by the objective measurements. PMID- 11203764 TI - Prediction of treatment-seeking behavior in acute TMD patients: practical application in clinical settings. AB - AIMS: To determine potential differences in predictive models of acute temporomandibular disorder (TMD) patients divided into groups based on the physiologic characteristics of their TMD. METHODS: One hundred seventy-seven acute TMD patients were evaluated with an extensive battery that included biologic and psychosocial measures. Subjects were separated into 3 groups based on a physical exam using the Research Diagnostic Criteria for TMD (RDC): those with a myofascial pain diagnosis, those with either a disc displacement or other joint condition, and those who reported pain but did not receive an RDC Axis I diagnosis. Six months later, it was determined whether patients had sought additional treatment for relief of their symptoms. Treatment-seeking and non treatment-seeking groups were compared for significant differences, and predictive models were generated to determine the array of variables that best predicted treatment-seeking behavior among each of the 3 classifications of TMD patients used in this study. RESULTS: Among patients with a diagnosis of myofascial pain, gender, Multidimensional Pain Inventory (MPI) interference score, and MPI affective distress score accurately predicted treatment-seeking behavior in 76.1% of the sample. For patients with a diagnosis of disc displacement, arthralgia, arthritis, or arthrosis, the following variables predicted treatment utilization behavior in 93.6% of the sample: race, RDC graded chronic pain, and the introversion scale of the Minnesota Multiphasic Personality Inventory-2. For patients with no RDC Axis I disorder, 80.5% of the sample was accurately classified with regard to treatment-seeking behavior through the use of only the characteristic pain intensity score (i.e., mean of visual analog scale scores for "pain right now," "worst pain," and "average pain"). CONCLUSION: The factors that predict which acute TMD patients are most likely to seek additional treatment vary depending on the physiologic basis of their TMD. This suggests that acute TMD patients may benefit from different modalities of treatment, depending on the type of TMD with which they present. PMID- 11203766 TI - Moving TMJ research into the 21st century. First annual scientific meeting of the TMJ Association Bethesda, Maryland, May 22-23, 2000. PMID- 11203765 TI - A longitudinal epidemiologic study of signs and symptoms of temporomandibular disorders from 15 to 35 years of age. AB - AIMS: To study the development over 20 years of signs and symptoms of temporomandibular disorders (TMD) in an epidemiologic sample and to analyze possible correlations between these signs and symptoms and some other variables. METHODS: The original group comprised 135 randomly selected 15-year-old subjects who were examined clinically and by means of a questionnaire for signs and symptoms of TMD. The examination was repeated after 5, 10, and 20 years by the same methods. After 20 years, when the original group had reached the age of 35 years, 124 individuals (92%) could be traced, and they were sent a questionnaire and invited for a clinical examination. The response rate was high: 114 subjects (92%) completed and returned the questionnaire, and 100 subjects (81%) attended the clinical examination. RESULTS: There was a substantial fluctuation of both reported symptoms and clinically recorded signs over the 20-year period, but progression to severe pain and dysfunction of the masticatory system was rare. In both the 15-year-old and 35-year-old subjects, 13% reported 1 or more frequent TMD symptoms. At age 35, only 3 subjects (3%) were classified as having severe or moderate clinical signs of dysfunction according to the Helkimo Index, fewer than in previous investigations. Women reported TMD symptoms and headache and had muscle tenderness and joint sounds more often than men. Correlations between the studied variables were mainly weak. Among the highest correlations found (rs = 0.4) were those between reported clenching and bruxing habits and TMJ sounds and jaw fatigue. CONCLUSION: In this epidemiologic sample followed from age 15 to 35 years, a substantial fluctuation of TMD signs and symptoms was found over time. Progression to severe pain and dysfunction was extremely rare. PMID- 11203767 TI - Regarding dinosaurs. PMID- 11203768 TI - American Academy of Gold Foil Operators. Clinician of the year award. Dr. William T. Pike. PMID- 11203769 TI - American Academy of Gold Foil Operators. Distinguished Member Award. Dr. K. Harris. PMID- 11203771 TI - Clinical evaluation of a resin-modified glass ionomer adhesive system--results at three years. AB - One hundred non-carious cervical lesions were restored with either Silux Plus or Estio LC resin composite using Fuji Bond LC as the bonding agent. Thirteen patients of mean age 60.5 years participated in the study. The retention rate at three years was: Silux Plus, 94%; Estio LC, 100%; total, 97%. Marginal discoloration of aesthetic significance was present around three restorations, two of which were in one patient. PMID- 11203770 TI - Two-year clinical performance of a polyacid-modified resin composite and a resin modified glass-ionomer restorative material. AB - This study compared the clinical performance of a polyacid-modified resin composite and a resin-modified glass-ionomer restorative material over two years. Thirty-four pairs of restorations of Compoglass and Fuji II LC were placed in caries-free cervical erosion/abfraction lesions without tooth preparation. Restorations were clinically evaluated at baseline, 6, 12, 18 and 24 months using modified Ryge/USPHS criteria. A significantly higher incidence of failed restorations was found with the polyacid-modified resin composite (p < 0.05). PMID- 11203772 TI - Selected mechanical properties of fluoride-releasing restorative materials. AB - Mechanical properties, diametral tensile strength (DTS) and flexural strength (FS) of six fluoride releasing materials were measured and compared. The samples were prepared and tested according to ISO specifications. The materials included a glass ionomer (Fuji IX), a resin-modified glass ionomer (Photac-Fil), two compomers (F 2000; Dyract AP) and two composites (Solitaire; Tetric Ceram). The tests were performed after the materials were stored in distilled water (DTS) and phosphate buffered saline solution (FS) at 37 degrees C for 24 hours and one week. Fluoride-releasing composite resin had the highest flexural and diametral tensile strengths and were statistically stronger than compomers, followed by resin-modified glass ionomer and conventional glass ionomer. However, a notable exception to this general trend was Solitaire, a fluoride-releasing composite resin. PMID- 11203773 TI - Influence of the direction of tubules on bond strength to dentin. AB - This study investigated the influence of the direction of dentinal tubules on resin-dentin tensile bond strength (mu TBS) using four commercially available bonding systems and observed the resin-dentin interfaces with an SEM. The dentin bonding systems used in this study were Clearfil Liner Bond II (LB, Kuraray), Imperva Fluoro Bond (FB, Shofu), Single Bond (SB, 3M) and One-Step (OS, BISCO). Thirty-six extracted caries-free human molars were used for micro tensile bond testing and eight additional teeth were used for scanning electron microscopy (SEM). The teeth were divided into two groups according to the direction of the dentinal tubules at the resin-dentin interface: a perpendicular group, in which the occlusal enamel was removed perpendicular to the long axis of the tooth, and a parallel group, in which the mesial half of the tooth was removed parallel to the long axis of the tooth, and the coronal dentin surface was used for bonding. After the flat dentin surfaces were polished with #600 silicon carbide paper, each surface was treated with one of the four adhesive systems according to the manufacturer's recommendation, then covered with resin composite (Clearfil AP-X, Kuraray) to provide sufficient bulk for micro-tensile bond testing. After 24 hours in 37 degrees C water, the resin-bonded teeth were serially sliced perpendicular to the adhesive surface, the adhesive interface trimmed to a cross sectional area of 1 mm2 and subjected to tensile forces at a crosshead speed of 1 mm/min. Statistical analysis of the tensile bond strengths were performed using two-way ANOVA and Fisher's PLSD test at 95% level of confidence. The tensile bond strength of the group with tubules parallel to the bonded interface was higher than that of tubules cut perpendicularly. This tendency reached statistical significance using SB and OS. PMID- 11203774 TI - Comparative in vivo and in vitro investigation of interfacial bond variability. AB - This comparative in vivo/in vitro study investigated the interfacial adaptation between dentin and composite resins in totally bonded adhesive restorations placed under clinical and laboratory conditions in the same tooth. Cavities were prepared in buccal or lingual surfaces of 47 third-molar teeth scheduled for extraction and randomly assigned for treatment with the following bonding systems/restorative materials: Clearfil Liner Bond 2/Clearfil AP-X (Group I, n = 10), Resulcin AquaPrime + Monobond/MFR Merz (Group II, n = 9), Prime&Bond 2.1/Dyract AP (Group III, n = 9), Scotchbond Multi-Purpose/Z-100 (Group IV, n = 10), and Ecusit Primer AB-Mono/Ecusit (Group V, n = 9). In Group V, a thin layer of a low-viscous compomer (Primaflow) was interposed between the dentin and the composite resin during restoration placement (according to the manufacturer's directions). After extraction a second filling was placed in each tooth with identical materials in the same manner as in vivo. The restoration-dentin interface was evaluated in longitudinally cut sections of the specimens by SEM analysis, and the frequency of gap formation between restoration and dentin was calculated. Median percentages for the in vivo/in vitro frequency of interfacial gap formation were 29.2%/13.9% in Group I, 33.3%/20.0% in Group II, 40%/5.3% in Group III, 53.9%/30.4% in Group IV and 13.8%/0% in Group V. Comparison of gap formation frequency between fillings placed in vivo and in vitro revealed significant differences (p < 0.05) in Groups II, III and IV. However, in Groups I and V the internal adaptation was not significantly different between in vivo and in vitro applied restorations. A significant (p < 0.01) correlation (Spearman-Rho rank correlation coefficient) was found for the corresponding in vivo and in vitro fillings placed in the individual teeth with regard to interfacial gap formation. It was concluded that achievement of a completely gap-free internal adaptation between restorative material and dentin in totally bonded composite resin restorations is difficult to predict under in vivo as well as in vitro conditions. PMID- 11203775 TI - Inhibition of artificial secondary caries in root by fluoride-releasing restorative materials. AB - This investigation evaluated the fluoride-releasing properties of various fluoride-releasing restorative materials, including resin-modified glass-ionomer cements (Fuji ionomer TypeII LC, Photac-Fil Aplicap, Vitremer), compomers (Ionosit FIL, Compoglass, Dyract) and fluoride-releasing resin composites (Heliomolar radiopaque, Degufill mineral). The study also estimated the effects of those materials on the inhibition of artificial secondary caries around restorations using a bacterial caries-inducing system. The amount of fluoride released from the materials in deionized water was measured every one week for 10 weeks. Class V cavities with the gingival margin located in the root were prepared in extracted human premolars and restored with each of the materials. The restored teeth were incubated in the bacterial artificial caries chamber, and the artificial lesion created around the restoration was observed microradiographically. The resin-modified glass-ionomer cements released the largest amount of fluoride and created a thick radio-opaque zone in the artificial lesion along the restoration-dentin interface. These results indicated that the fluoride-releasing restorative materials have the potential to inhibit secondary caries formation around restorations. Resin-modified glass-ionomer cements presented a particularly strong effect, compared with compomers and fluoride-releasing resin composites. PMID- 11203776 TI - Shear bond strength of four filled dentin bonding systems. AB - This study compared the shear bond strength of four filled dentin bonding agents (Prime & Bond NT, One Coat Bond, OptiBond Solo, PermaQuik1) to a conventional unfilled Dentin Bonding agent (3M Scotchbond Multipurpose Plus). A column of composite resin (Herculite XRV Restorative Resin) was bonded to human dentin using the five dentin-bonding systems following the manufacturers' directions. The specimens were thermocycled 1000 cycles from 6 to 60 degrees C. Each specimen was tested on an MTS machine in shear-to-failure. The data were subjected to One Factor ANOVA and Newman-Kuels post-hoc tests. Statistical analysis revealed that One Coat Bond had significantly greater shear bond strength than all other materials tested. PMID- 11203777 TI - Effect of delayed application on shear bond strength of four fifth-generation bonding systems. AB - This study compared the shear bond strength of four adhesives dispensed 10 minutes prior to use to immediate dispensing and use. For half (40) of the specimens (n = 10), four different dentin bonding agents (One Coat, Bisco One Step, Prime & Bond 2.1 and 3M Single Bond) were used to bond a column of composite resin (Z100 Restorative Resin) to the dentin surface following manufacturers' directions and using the dentin bonding agent immediately after dispensing. For the remaining specimens, the same procedure was followed except that the dentin-bonding agent was dispensed 10 minutes prior to use. All specimens were tested two weeks after bonding on a MTS machine. The data obtained was subjected to Two-factor ANOVA and Tukey-B post-hoc tests. The statistical analysis showed that there was no significant difference between the control groups and the experimental groups, although the dentin bonding agents containing acetone showed a trend toward lower bond strengths when not used immediately after dispensing. PMID- 11203778 TI - In vitro evaluation of secondary caries development in enamel and root dentin around luted metallic restoration. AB - Materials that release fluoride have been recommended for patients with high caries risk, but there is no conclusive evidence of their effect on fixed prostheses abutments. This study evaluated the influence of a resin-modified glass-ionomer cement on in vitro caries development in enamel and root dentin around metallic restoration. The cervical portion of 12 human third molars were sectioned in four blocks that were randomly divided into four Groups (n = 12; 1 block from each tooth/group): ZP (restoration + zinc phosphate cement), GI (restoration + resin-modified glass-ionomer cement), C1 (no restoration and no pH cycling), and C2 (no restoration and pH cycling). In ZP and GI, metallic restorations were luted at the crown-root junction. ZP, GI and C2 were submitted to a pH-cycling model. All blocks were sectioned, embedded and polished. Enamel and root dentin demineralization were evaluated through cross-sectional microhardness Knoop measures at 20 to 80 microns of depth (from the outer surface) and at 20 to 220 microns of distance from the cavity margins. Mineral loss values were calculated from Knoop hardness numbers. Data were analyzed by ANOVA, Tukey's test and regression analysis. Groups ZP, GI and C2 showed demineralization in relation to C1, which was more superficial in enamel than in root dentin. In root dentin, mineral loss in ZP and GI was smaller than in C2. Distance from the cavity margins was not significant. There was no difference between resin-modified glass-ionomer cement and zinc phosphate cement regarding artificial secondary caries development in both dental substrates. PMID- 11203779 TI - Microleakage at the cervical margin of composite Class II cavities with different restorative techniques. AB - This study evaluated the microleakage at the cervical margins of Class II composite resin restorations restored with different techniques. Slot cavities were prepared on both proximals of 40 unerupted third molars with one cervical margin located above and the other below the cementoenamel junction. The prepared teeth were randomly assigned to four groups and restored using the following techniques: (I) 3-Sited, (II) Directed-Shrinkage, (III) Resin-Modified Glass Ionomer Cement or a (IV) Flowable Composite as the gingival increment. All restorations were placed with the same bonding agent and composite resin. The difference among the groups was on the first increment and on its insertion and polymerization techniques. After restoration, the teeth were thermocycled and exposed to a dye. Results showed that all the techniques worked well for enamel, with almost no leakage. However, on cementum, all techniques demonstrated moderate to severe leakage. PMID- 11203780 TI - The effect of additional enamel etching and a flowable composite to the interfacial integrity of Class II adhesive composite restorations. AB - This in vitro study evaluated the interfacial integrity of Class II resin composite restorations. The influence of a flowable composite and additional enamel etching was also evaluated. Deep, saucer-shaped Class II cavities were prepared in the mesial and distal proximal surfaces of 25 extracted human molars and assigned to five treatment groups. The gingival margins were extended to approximately 1 mm above the CEJ in 40 cavities and below the CEJ in 10 cavities. The prepared cavities were then restored with a self-etching primer system (Clearfil Liner Bond II) and a hybrid resin composite (Clearfil AP-X), with and without a flowable composite (Protect Liner F) and additional enamel etching with 37% phosphoric acid gel (K-etchant). After finishing, polishing and thermocycling (4 and 60 degrees C, x300), the samples were longitudinally sectioned through the restorations and resin-tooth interfaces were observed directly under a laser scanning microscope. Statistical analysis indicated that the use of a flowable composite produced significantly more (p = 0.04) gap-free resin-dentin interfaces than teeth restored without the flowable composite. However, both flowable composite and enamel etching could not prevent gap formation at enamel-resin interfaces and crack formation on enamel walls. PMID- 11203782 TI - Fracture resistance of anterior, posterior and universal light activated composite restoratives. AB - This investigation measured the fracture resistance of a wide range of currently available light-activated-composite restoratives. Products intended solely for anterior use were tested together with universal materials and products intended for posterior application. All materials were handled according to manufacturers' instructions. For products evaluated in this investigation, universal and posterior materials yielded higher mean torque to fracture (T) values overall in comparison to the anterior products. One Microfilled and two Polyglas filled products designated for posterior application yielded relatively modest mean fracture resistance values. PMID- 11203781 TI - Amalgam bonding: visualization and clinical implications of adhesive displacement during amalgam condensation. AB - Resin adhesive was visualized in this in vitro study of amalgam bonding using methylene blue dye incorporated into the resin or by scanning electron microscopy. Class II amalgam cavities were prepared in extracted teeth previously stored in buffered formalin. The preparations were then restored following manufacturers' instructions, but included methylene blue dissolved in ethanol into the adhesive resin mixture. This procedure had little effect on the setting time of the resin. Following condensation and carving, excess resin was incorporated into the body of the restorations as well as onto all adjacent coronal surfaces with significant occlusal and proximal accumulations. Resin also accumulated in significant amounts on the gingival floor of the proximal box and at line angles and retentive grooves within the preparation. In conclusion, radiological studies demonstrated that artifacts produced by resin accumulation at the gingival floor of the box could be mistaken for an open margin or recurrent caries. Other potential clinical consequences of resin residue on tooth surfaces are discussed, including the problem of interproximal ledges and occlusal discrepancies. The incorporation of a radiopaque material in the resin systems should be a universal requirement. PMID- 11203783 TI - Relationship between adhesive thickness and microtensile bond strength. AB - This study evaluated the effect of the thickness of the adhesive resin layer of two commercially available resin bonding systems on bond strengths (Single Bond and Liner Bond 2V). The adhesive of Single Bond contains ethanol and water as solvents and is applied using the moist-bonding technique. The adhesive of Liner Bond 2V contains no solvents and is applied after a self-etching primer treatment. Forty-six caries-free molars were ground flat to expose the dentin surface and polished with #800-grit silicon carbide paper under running water. A vinyl tape punched with a 6 mm diameter hole was then placed on the dentin surface to demarcate the area for bonding. The thickness of the adhesive resin layer was varied by stacking an increasing numbers of vinyl tapes together. The teeth were randomly divided into two groups and treated with either Clearfil Liner Bond 2V or Single Bond. They were further divided into subgroups according to the number of tapes placed on the dentin surface. After the bonding procedures the teeth were incrementally restored with Clearfil AP-X resin composite, building a 5 mm high crown to produce sufficient bulk for the microtensile bond test and stored in tap water at 37 degrees C for 24 hours. The teeth were then sectioned along their long axis into 0.7 mm thick slabs and trimmed for the microtensile bond test using a super-fine diamond bur. The thickness of the adhesive resin layer was then measured with a light microscope and the slabs tested in tension at a crosshead speed of 1 mm/minute. The results were subjected to statistical analysis by a one-way analysis of variance and linear regressions with 95% confidence intervals. The thickness of the Clearfil Liner Bond 2V adhesive layer ranged from 5 mm-1500 mm, and for Single Bond, it varied from < 7.5 mm-430 mm. For Clearfil Liner Bond 2V, bond strengths increased significantly as the thickness of bonding layer increased (p < 0.05). However, the bond strengths of the Single Bond decreased significantly with increased thickness of the bonding layer (p < 0.05). PMID- 11203784 TI - Long-term effect of dentin primers on enamel bond strength and marginal adaptation. AB - Contamination of etched enamel with dentin adhesive systems is unavoidable in clinical situations. The aim of this in vitro study was to evaluate the long-term effect of dentin adhesives and application technique on resin composite bond strength and marginal adaptation to enamel. Six hundred freshly extracted mandibular bovine incisors were used. Three hundred teeth were flat ground, and the enamel was etched for 30 seconds with 32% phosphoric acid. The etched surface was treated by different dentin adhesive systems with and without intensive rubbing by use of application brushes. As a control, only the enamel adhesive resin was applied and air thinned. Furthermore, contamination with saliva was performed after the etching process. Etched and silanated CEREC blocks were bonded onto the enamel specimens with different adhesive resins and stored for 1 and 365 days (37 degrees C, aqua dest). After storage, the specimens were thermocycled for 24 hours (1150 cycles between 5 degrees C and 55 degrees C), and subjected to shear bond testing. Three hundred box-shaped cavities were prepared on buccal surfaces of the incisors and filled with one resin composite using the same pretreatment modes as in the shear bond test groups. After 1 and 365 days of storage, a margin analysis was performed using a SEM (X200 magnification). Dentin adhesive systems did not show an adverse effect on long-term enamel bond strength and marginal adaptation. Rubbing application of the primers decreased the bond strength by values of approximately 20% after 24 hours and approximately 40% after 1 year of storage. Marginal adaptation showed 94-98% gap-free margins in the control and dentin adhesive system-only groups; however, after rubbing of primers, the proportion of gap-free margins decreased significantly to 85-88%. The lowest bond strength (8-10 MPa) and margin quality (49-69% gap-free margins) were recorded for the groups with saliva contamination. PMID- 11203785 TI - Bond strengths of single-bottle dentin adhesives to caries-affected dentin. AB - There is concern that some acidic conditioners may not be strong enough to adequately etch sclerotic or caries-affected dentin. The hypothesis that was tested was that there were no significant differences in the bond strengths of single-bottle bonding systems to normal or caries-affected dentin, regardless of the strength of the phosphoric-acid conditioner. Extracted teeth with coronal caries extending into mid-dentin were prepared by grinding the occlusal surface flat. This left a central region of caries-affected dentin surrounded by normal dentin. The One-Step bonding system was used to bond dentin following etching with 10 or 32% phosphoric acid. The Single Bond system was used after etching dentin with 10 or 35% phosphoric acid. After 24 hours in water, serial vertical sections were made through the bonded teeth to create slabs 0.7 mm thick. Each tooth yielded four to five slabs, some of which included normal dentin, while others included caries-affected dentin. Each slab was trimmed into an hourglass configuration to limit the test area to normal or caries-affected dentin. The results obtained with One-Step following etching with 10% phosphoric acid showed lower (P < 0.05) tensile bond strengths to caries-affected dentin compared to normal dentin (36.9 +/- 8.0 MPa vs 47.7 +/- 6.5 MPa, respectively). This difference disappeared when using 32% phosphoric acid (49.7 +/- 6.1 MPa vs 45.0 +/- 7.2 MPa, respectively). Bonds made to caries-affected dentin with Single Bond were always lower than bonds to normal dentin regardless of the strength of the phosphoric acid. Scanning electron microscopy of polished cross sections sequentially challenged with acid and NaOCl revealed loss of the middle of the hybrid layers created by either bonding system in caries-affected dentin etched with 10% phosphoric acid. It is clear that 32-35% phosphoric acid is required to adequately etch caries-affected dentin in order to produce high bond strengths and well-infiltrated demineralized dentin. PMID- 11203786 TI - Fluoride release from three glass ionomers, a compomer, and a composite resin in water, artificial saliva, and lactic acid. AB - The amounts and the pattern of fluoride release from one metal-reinforced glass ionomer cement, two resin-modified glass ionomer cements, one compomer, and one composite resin placed in double-distilled water, artificial saliva, and lactic acid were evaluated in this study. Measurements of fluoride ion release were made for a total of 105 cylindrical specimens (10 mm in diameter and 1.5 mm in height). They were taken over a period of 16 weeks at the intervals of 4, 8, 12, and 24 hours, as well as 2, 3, 7, 14, 28, 56, and 112 days. The pattern of fluoride release was similar for all of the examined materials. The greatest amount of fluoride was released from the metal-reinforced glass ionomer Argion. The resin-modified glass ionomers Vitremer, Fuji II LC; the compomer Dyract; and the composite resin Tetric followed in ranking order. The pH of the environment strongly affected the fluoride release from the materials. There was a significant difference (P < 0.001) in the amounts of fluoride released in lactic acid vs water and artificial saliva, whereas, there was no significant difference (P > 0.05) in the amounts of fluoride released in water vs artificial saliva. PMID- 11203787 TI - Marginal adaption of Class V restorations with and without "softstart polymerization". AB - Polymerization shrinkage causing marginal gap formation is still a major problem in light curing restorations. The aim of the present study was to test the influence of "softstart polymerization" (prepolymerization at a low light intensity followed by a final cure at a high light intensity) on the marginal integrity of polyacid-modified resin and composite resin restorations in Class V cavities using a commercially available curing unit with two defined curing intensities. Sixty standardized Class V cavities were prepared. Twenty cavities at a time were filled either with a composite resin [Spectrum + Prime & Bond 2.1 (SP)], or with polyacid-modified resins [Dyract + Prime & Bond 2.1 (DY); Hytac + OSB Primer (HY)]. Ten fillings of each group were either conventionally cured (40 seconds, 800 mW/cm2), or they were cured with a lower starting intensity (10 seconds, 150 mW/cm2) and then with the full intensity (30 seconds, 800 mW/cm2). Margins were evaluated before and after thermomechanical loading (TCML) by quantitative margin analysis. Microleakage was assessed by dye penetration. The softstart polymerization showed no significant influence on gap formation for each material and interface before and after TCML. Quantitative margin analysis after TCML showed significantly fewer marginal gaps at the enamel/restoration interface for SP (0%) compared to DY (15.5%) and HY (44.5%) using softstart polymerization. At the dentin/restoration interface the corresponding results for gap formation were 29.6% for SP, 8.5% for DY, and 21.0% for HY. These results were not significantly different from each other. Dye penetration was significantly higher for SP at the dentin/restoration interface. SP showed significantly more marginal swelling at the dentin/restoration interface compared to DY. In conclusion, softstart polymerization using a very low starting intensity did not improve the marginal adaptation of polyacid-modified resins or composite resins in Class V cavity preparations. The best marginal adaptation in Class V cavities at the enamel/restoration interface was achieved with SP, using the acid-etch technique. In dentin, however, the polyacid-modified resins showed a superior marginal adaptation. PMID- 11203788 TI - Effect of cavity form and setting expansion of refractory dies on adaptability of fired ceramic inlays. AB - The purpose of this study was to investigate the effect of cavity form and setting expansion of refractory die materials on the adaptability of fired ceramic inlays. Standardized Class I cavities with three kinds of lateral wall divergences (10 degrees, 20 degrees, and 30 degrees) and three kinds of surface roughness were prepared in epoxy resin blocks. A refractory die was prepared from an impression of the epoxy resin cavity, whose setting expansion ranged from 0.01 to 1.13%. A ceramic inlay was fired on each die. The fabricated inlay was inserted into the epoxy resin cavity, and the interfacial distance between the ceramic inlay and the cavity wall at the margin was measured using a reflecting microscope at X100 magnification. The internal fit was measured after sectioning the specimen longitudinally. The results were analyzed by ANOVA and Sheffe's F test. Good adaptation was achieved with the smooth-surface cavity. The adaptability depended on the angle of the cavity divergence, and small gaps were observed in 20 degrees and 30 degrees cavities (P < 0.05). The inlays fabricated on the refractory dies with a small setting expansion demonstrated small internal gaps. Significantly good adaptation was achieved when the setting expansion was less than 0.2% (P < 0.05). The results indicated that the cavity form and the setting expansion of the refractory die material had significant effects on the adaptability of fired ceramic inlays. PMID- 11203789 TI - Dentin bond strength and marginal adaption after NaOCl pre-treatment. AB - The aim of this in vitro study was to compare the dentin bond strength and marginal adaptation of direct composite resins with and without additional NaOCl treatment after the etching process. A total of 150 cavities were prepared into disks of freshly extracted human third molars and filled with direct composite resins. Dentin adhesives of the fourth (with total etching: Scotchbond Multi Purpose Plus, EBS, and Solid Bond), and fifth generation (one-bottle adhesives: Prime&Bond 2.1, Syntac Sprint) were used in combination with corresponding composite resin materials. Dentin disks without cavity preparation treatment served as controls. After 24 hours of storage and 24 hours of thermocycling (1150 cycles), replicas were made and push-out testing was performed. Replicas were examined regarding marginal adaptation using SEM (X200 magnification). In general, fourth-generation dentin adhesives produced better results in bond strength and marginal adaptation than fifth-generation one-bottle systems (P < 0.05). Within the fourth generation, Scotchbond Multi-Purpose Plus and EBS achieved significantly higher push-out values and percentages of gap-free margins than Solid Bond (P < 0.05). After hypochlorite treatment, dentin bond strength ( 25%) and marginal adaptation (-30%) decreased significantly (P < 0.05) in all groups. PMID- 11203790 TI - Two-year clinical comparison of a microfilled and a hybrid resin-based composite in non-carious Class V lesions. AB - The purpose of this double-blind clinical trial was to compare the retention rate in noncarious Class V lesions of two resin-based composite restorative materials with contrasting stiffness. Isolation with retraction cord, pressed paper triangles, and cotton rolls was used to closely mimic the procedures generally used in a practice setting. Thirty pairs of restorations were placed, one using Silux Plus and one using Z100. The assignment of material was randomized, and the subjects were unaware of the material used. All restorations were placed with a fourth-generation adhesive liner, Scotchbond Multi-Purpose. Evaluations were performed at baseline, 6, 12, 18, and 24 months by two independent examiners using criteria developed by Cvar and Ryge in a forced consensus model. Examiners were unaware of the restoration's group identity. No difference between the retention rates for the two groups was found after 24 months, bringing into question the role that a material's stiffness plays in determining retention in a noncarious Class V lesion. PMID- 11203791 TI - Effect of dentin primer on shear bond strength of composite resin to moist and dry enamel. AB - The etched enamel-composite resin bond is the most reliable bond known to us. Moisture and dentin primers are the two most important variables that can interfere with this bond. This study investigated the effect of dentin primer on bond strengths of composite resin to moist and dry enamel. One hundred freshly extracted molar teeth were used for shear bond strength testing. The teeth were mounted in phenolic rings with an approximal enamel surface exposed. The exposed enamel surface on each tooth was flattened using 320- 400- and 600-grit silicon carbide papers and etched using 34-38% phosphoric acid gel. The teeth were then divided into 10 groups (n = 10). Four groups were assigned to each of the two dentin bonding systems, Scotchbond Multi-Purpose and OptiBond FL. Two groups were assigned to the single-bottle bonding agent (Single Bond). Each bonding system was tested on moist and dry enamel. OptiBond FL and Scotchbond MP were tested with and without the use of primer. All samples were thermocycled and tested in shear. Fracture analysis was performed using a binocular microscope. For scanning electron microscopy, approximal samples of enamel (1 mm thick) were flattened, etched, and bonded with and without primer on moist and dry enamel. A 1 mm-thick layer of Z100 was bonded to the specimens, which were then immersed in 10% HCl for 24 hours to dissolve the enamel. The specimens were viewed under a scanning electron microscope. Results indicated that the use of primer on dry enamel did not significantly affect (P > 0.05) shear bond strengths for the two bonding systems, Scotchbond MP (primed 24.10 +/- 4.83 MPa, unprimed 29.57 +/- 7.49 MPa) and OptiBond FL (primed 26.82 +/- 4.44, unprimed 25.66 +/- 2.95). However, the use of primer was found to be essential on moist enamel to obtain acceptable bond strengths with both Scotchbond MP (primed 25.61 +/- 10.29 MPa, unprimed 3.26 +/- 0.95 MPa) and OptiBond FL (primed 30.28 +/- 3.49 MPa, unprimed 8.37 +/- 3.31 MPa). Moisture on enamel did not significantly affect (P > 0.05) bond strengths for the single-bottle bonding agent, Single Bond (moist enamel 31.34 +/- 9.03 MPa, dry enamel 27.93 +/- 5.41 MPa). Fracture analysis revealed that most fractures were adhesive or mixed, with a greater percentage being cohesive for the groups with dry enamel or with primer on moist enamel. Scanning electron micrographs corroborated the shear bond strength data. The specimens without primer on moist enamel showed very poor penetration of adhesive and composite resin into the etched enamel microporosities. PMID- 11203792 TI - Operative Dentistry for the new millennium: a problem specific approach to operative dentistry. AB - This paper presents an alternate view of current preclinical education in Operative Dentistry and suggests a course that uses a cause and appropriate response action rather than the traditional material specific cavity preparation. This approach considers caries as a disease, could foster a better understanding of prevention and its application in maintaining teeth for a lifetime for the patient, and encourage critical thinking for both student and faculty. PMID- 11203793 TI - Excellence in diagnosing failures: a challenge for the 21st Century. PMID- 11203794 TI - American Academy of Gold Foil Operators Distinguished Member Award. Dr Norman C Ferguson. PMID- 11203795 TI - Custom provisional restorations: simple, fast and accurate. PMID- 11203797 TI - Effectiveness of polymerization in composite restoratives claiming bulk placement: impact of cavity depth and exposure time. AB - The impact of variation of cavity depth and light-source exposure time upon the effectiveness of polymerization of two "bulk placement" composite restoratives was assessed indirectly using hardness testing. The current investigation used a digital microhardness tester to evaluate hardness gradient between top and bottom surfaces of composite specimens of various depths after different light-exposure times. The results showed that the effectiveness of polymerization decreased significantly with increased cavity depth regardless of exposure time. Increased exposure time increased the extent of polymerization at cavity depths of 3 to 4 mm. Increments of the composites evaluated should be no greater than 2 mm to provide uniform and maximum polymerization. PMID- 11203796 TI - Fluoride uptake around cavity walls; two-dimensional mapping by electron probe microanalysis. AB - This study reports fluoride uptake around the cavity wall of teeth by two dimensional mapping. Fluoride concentration was measured using the wavelength dispersive x-ray analysis (WDX) method. The buccal cavity wall of a human tooth was coated five times with 2% sodium fluoride solution at three-day intervals for 12 days, and then immersed in a normal saline solution at 37 degrees C. After one month, the tooth was bisected longitudinally through the center of the cavity surface perpendicular to the axial wall. On the polished surface of the cut tooth, the fluoride concentration was measured. Fluoride distribution maps around the cavity wall were drawn using a bundle of the observed analytical lines. Fluoride uptake from fluoride-releasing materials (conventional glass-ionomer cement, light-cured glass-ionomer cement, light-cured composite resin, light cured bonding agent) around the cavity wall was investigated using the same method. The maps showed higher fluoride uptake in dentin than in enamel and a strong location dependence of fluoride uptake in a tooth, especially in the dentin. Fluoride uptake from the resin was greater than that from the cement. It was summarized from these results that a two-dimensional map of fluoride uptake can provide valuable information on the cariostatic properties of fluoride releasing materials. PMID- 11203799 TI - The full gold crown: an overview. PMID- 11203798 TI - Bonding of amalgam restorations: existing knowledge and future prospects. AB - A number of laboratory and clinical studies over the last 15 years have explored the potential advantages of bonding amalgam to tooth surfaces. Bond strengths have been reported to range from 2 to 20 MPa, with higher bond strengths reported for filled adhesives. Most studies agree that the use of bonding results in a considerable reduction of microleakage, when compared with copal varnish or no lining. The use of bonding provides retention in vitro that is equivalent to, or better than, the use of mechanical undercuts. Most studies on strength of restored teeth report an improvement in resistance to fracture or cuspal flexing as measured by strain gauges. Penetration of secondary caries along the interface has been found to be inhibited by bonding. The mode of failure of bonded amalgams has generally been reported to be mixed, but predominantly between the resin and amalgam. In vitro studies have reported one potential problem in the incorporation of resin into amalgam, which may cause a decrease in strength of the restoration. The clinical studies of bonded amalgams that have been published to date are of short duration, indicating that when traditional preparations are used, no problems are seen with bonding, but also no advantages, as measured by clinical assessment criteria. However, some studies show that bonded amalgam may be useful for procedures where non-bonded amalgams would be expected to be lost, namely in preparations with little, if any, mechanical retention. It was concluded that, while there are various in vitro studies demonstrating that bonded amalgams have advantages of improved retention and tooth reinforcement and decreased marginal microleakage and secondary caries, the operative technique is more complicated and there are few advantages yet evident from clinical studies in conventional preparations having mechanical retentive features. However, there is evidence accruing from clinical studies that bonding of amalgam can be favorably used to extend the range of usage of amalgam to non-retentive conservative preparations, and toward the other extreme, as an adjunct to other forms of retention in large compound restorations. PMID- 11203801 TI - E-Z gold for repair of abraded and eroded cusp tips. PMID- 11203802 TI - Progress and decline. PMID- 11203803 TI - Durability of enamel bond strength of simplified bonding systems. AB - The purpose of this study was to investigate the influence of thermal cycling on enamel bond strength of 2-step bonding systems. The systems used were self etching primer systems; Imperva Fluoro Bond, Clearfil Liner Bond II, and Mac Bond II; and self-priming adhesive systems; One Step, OptiBond Solo, Prime & Bond 2.0, and Single Bond. Bovine mandibular incisors were mounted in self-curing resin and the facial surfaces were wet ground with #600 SiC paper. Enamel surfaces were treated following each manufacturer's instructions. Adhesives were applied and composites were condensed into a Teflon mold (phi 4 x 2 mm) and light cured. Bonded specimens were divided into four groups; stored in 37 degrees C water for 24 hours, followed by thermal cycling between 5 degrees C and 60 degrees C for 3,000, 10,000, and 30,000 cycles. Ten samples per test group were tested in shear mode at a crosshead speed of 1.0 mm/min. One-way ANOVAs followed by Duncan's multiple range test (p < 0.05) were done. For self-etching primer systems, a significant decrease in bond strength was observed for the thermal cycling groups. For the self-priming adhesive systems, a small decrease in bond strength was observed but no significant differences were found for thermal cycling groups. The changes in bond strength after thermal cycling were different between the bonding systems. PMID- 11203804 TI - Microhardness of carious deciduous dentin. AB - The purpose of this study was to measure the microhardness values of deciduous dentin and to compare the values as a function of position in the caries-affected layers of dentin including transparent, adjacent sound dentin, and dentin regions far from and not related to caries. Seven extracted or exfoliated deciduous anterior teeth that had dentin caries on a proximal surface were sectioned parallel to the long axis of the tooth. Ten sectioned and polished specimens were dehydrated and dried. Microhardness was measured with a Knoop indenter and correlated with wet-SEM micrographs. All data were statistically analyzed using a two-way ANOVA with subsequent Tukey-Kramer multiple comparison tests at p < 0.05. The hardness decreased from the dentinoenamel junction to the pulp chamber wall, except for the region under the caries. The hardness values of the region under the caries were significantly lower than those of other regions except for the inner region. For both the carious and sound sides, the hardness values of the inner region were significantly lower than those of the outer and middle regions. In comparing the hardness among regions in the carious and sound sides, the hardness of the outer, middle, and inner regions on the carious side was significantly lower than those in the sound side. PMID- 11203807 TI - Operative dentistry in the academic world. PMID- 11203806 TI - Polymerization shrinkage of visible-light-cured composites. AB - This study investigated the long-term dimensional changes of a conventional and a polyacid-modified composite resin and the effects of hydration on polymerization shrinkage. A strain-monitoring device was used to measure the linear polymerization shrinkage of the composites in the free state when stored in water at 37 degrees C or air at 26 degrees C over a one-month period. Results showed that the polymerization reaction of both conventional and polyacid-modified composite resins was accompanied by a dimensional shrinkage change. The rate of shrinkage for both composites was greatest during the polymerization reaction and continued after removal of the curing light. When stored in water, the greatest shrinkage was noted at one hour for both materials. This was followed by a slow uptake of water and expansion from one day to one month. The polyacid-modified composite had significantly less polymerization shrinkage than the conventional composite after one month of storage in water. PMID- 11203805 TI - Single-crystalline ceramic whisker-reinforced carboxylic acid-resin composites with fluoride release. AB - Currently available glass-ionomer, resin-modified glass-ionomer, and compomer materials have relatively low strength and toughness and, therefore, are inadequate for use in large stress-bearing posterior restorations. In the present study, ceramic single-crystalline whiskers were mixed with fluorosilicate glass particles and used as fillers to reinforce experimental carboxylic acid-resin composites. The carboxylic acid was a monofunctional methacryloxyethyl phthalate (MEP). Five mass fractions of whisker/(whisker + fluorosilicate glass), and corresponding resin (resin + MEP), were evaluated. Four control materials were also tested for comparison: a glass ionomer, a resin-modified glass ionomer, a compomer, and a hybrid composite resin. Flexural specimens were fabricated to measure the flexural strength, elastic modulus, and work-of-fracture (an indication of toughness). Fluoride release was measured by using a fluoride ion selective electrode. The properties of whisker composites depended on the whisker/(whisker + fluorosilicate glass) mass fraction. At a mass fraction of 0.8, the whisker composite had a flexural strength in MPa (mean +/- sd; n = 6) of 150 +/- 16, significantly higher than that of a glass ionomer (15 +/- 7) or a compomer control (89 +/- 18) (Tukey's multiple comparison test; family confidence coefficient = 0.95). Depending on the ratio of whisker:fluorosilicate glass, the whisker composites had a cumulative fluoride release up to 60% of that of a traditional glass ionomer. To conclude, combining ceramic whiskers and fluorosilicate glass in a carboxylic acid-resin matrix can result in fluoride releasing composites with significantly improved mechanical properties. PMID- 11203808 TI - The efficacy of reservoirs in bleaching trays. AB - Thirty patients were selected to bleach their maxillary teeth. Vacuum-formed trays were fabricated for the maxillary arch so that only one quadrant of bleaching tray had reservoirs. Nupro Gold 10% carbamide peroxide gel was given to patients. They were instructed to place a drop of gel in each tooth area and wear the trays twice a day for two-hour periods. After 10 days the patients were evaluated for shade changes in each quadrant. No clinical difference was observed in the after-shade match of the two quadrants. It appears that the addition of blockout spacers to create reservoirs does not increase the success of home bleaching. PMID- 11203809 TI - Three-year clinical evaluation of a polyacid-modified resin composite (Dyract). AB - The aim of this study was to clinically evaluate a polyacid-modified resin composite (Dyract; Dentsply deTrey). Forty-one Dyract restorations were placed (36 in noncarious cervical cavities and five in anterior approximal cavities), and assessed after three years. The retention rate was 97% for the cervical restorations; however, 16 restorations showed some degree of marginal discoloration, sometimes severe. Color match and surface integrity were highly satisfactory throughout the trial. Dyract has now been superseded by Dyract AP, and the manufacturers should consider recommending mandatory enamel etching. PMID- 11203810 TI - Short-term dentin bridging of mechanically-exposed pulps capped with adhesive resin systems. AB - Dentin bridging of 150 mechanically exposed monkey pulps to two adhesive resins [BondWell LC (BW); Clearfil Liner Bond II (LB)] and a calcium hydroxide cement [Dycal (DY)] were histopathologically evaluated at 3, 7, 14, 30, and 60 days after operation (n = 10). The dentin bridge structure was three-dimensionally reconstructed from serial sections using a computer-aided reconstruction system. At three and seven days, in all pulps, no necrotic tissue and slight inflammatory cell infiltration was observed just below the exposure site. At 14 days, spindle shaped fibroblast cells could be detected at the wound surface. All dentin chips showed reparative dentin deposition along the periphery of the wound surface. From this stage, the formation of secondary dentin from the pulpal wall at the periphery of the exposed area was recognized in all pulps. At 30 days, initial signs of dentin bridging were observed at the wound surface with a well-organized layer of odontoblastoid cells. The exposed area became occluded with a dentin bridge as the observation period increased. Group DY showed significantly higher incidence of dentin bridging than other groups at 30 days (p < 0.05). However, no significant difference of dentin bridge formation was found between Group DY and Groups BW and LB at 60 days. Bacterial penetration along the cavity walls and pulp tissue could not be detected in all groups. Histopathological observations and three-dimensional image analysis suggested that dentin bridge formation may occur following three patterns: (1) formed from the periphery of the residual dentin chip at the wound surface within 14 days, (2) formed within 14 days from the periphery of the cavity floor and with formation of reparative dentin by stimulation during the cavity preparation, and (3) formed from the wound surface within 30 days after exposure. PMID- 11203811 TI - Comparison of conventional vs self-etching adhesive bonds to caries-affected dentin. AB - The mechanism of resin adhesion to caries-affected dentin is still unclear. This study evaluated the interfacial morphology of two bonding systems to caries affected dentin, coupled with the measurement of microtensile bond strengths (mu TBS). Carious human molars were prepared as previously described in Nakajima and others (1995) and were bonded with Single Bond (SB) or FluoroBond (FB) according to the manufacturer's instructions, followed by creation of AP-X composite buildups. After one day of storage in 37 degrees C water, the teeth were serially sectioned vertically into 0.8 mm slabs, trimmed to yield a 1 mm2 test area, and tested to failure in a Bencor device used in an Instron machine operated at 1 mm/min. Resin-dentin interfaces were observed with SEM before or after acid/base challenge. Bonding to normal dentin with the two bonding systems (SB and FB) showed tensile bond strengths significantly higher than those to caries-affected dentin. The moist bonding technique significantly increased bond strength of SB to normal and caries-affected dentin. SEM examination revealed that typical hybrid layer and resin tags could not be formed to caries-affected dentin. The results suggested that resin penetration may be prevented by occlusion of dentinal tubules by mineral deposits that may also impart acid-resistance to the intertubular matrix of caries-affected dentin. PMID- 11203812 TI - Effect of food-simulating liquids on surface characteristics of composite and polyacid-modified composite restoratives. AB - The chemical environment is one aspect of the oral environment that could have an appreciable influence on the in vivo degradation of composite resins. The effects of food-simulating liquids on the surface roughness and hardness of composite (Silux Plus, Z100, Spectrum TPH, and P50) and polyacid-modified composite resins (F2000 and Dyract AP) were thus investigated and compared. Sixty disks of each material were made. Half were used for microhardness testing and the remaining half for studying surface roughness using profilometry. Each group of 30 disks was subdivided into six groups of five and conditioned for one week as follows- Group 1 (control): air at 37 degrees C; Group 2: distilled water at 37 degrees C; Group 3: 0.02 N citric acid at 37 degrees C; Group 4: 0.02 N lactic acid at 37 degrees C Group 5: heptane at 37 degrees C; Group 6: 50% ethanol-water solution at 37 degrees C. Data were analyzed using one-way ANOVA and Scheffe's test at a significance level of 0.05. Results showed that the surface roughness of all restoratives evaluated was not significantly affected by food-simulating liquids. No significant change in surface hardness was noted with conditioning of Spectrum TPH, Dyract AP, and F2000 in the various food-simulating liquids. The BIS-GMA based composites Silux Plus, Z100, and P50 appeared to be more susceptible to the softening effects of some food-simulating liquids. PMID- 11203813 TI - Effect of restoration size on fracture resistance of bonded amalgam restorations. AB - The purpose of this study was to determine the effect of restoration size on the fracture strength of amalgam restorations bonded with Amalgambond Plus (with HPA). Research has shown that this adhesive is dispersed throughout the unset amalgam during condensation and that a decrease in diametral tensile strength, proportional to the amount of adhesive incorporated into the unset amalgam, has resulted. Smaller cavity preparations have a higher ratio of surface area to volume than do larger preparations, and it was anticipated that a proportionately greater amount of adhesive would be incorporated into smaller amalgam restorations. Sixty extracted human molars were divided into four groups of 15 teeth and mounted in tray acrylic-filled PVC cylinders. Shallow approximo occlusal channels were prepared in two groups. One group was restored with Amalgambond Plus and Tytin amalgam, the other with just Tytin amalgam. Larger proximo-occlusal preparations were made in the remaining two groups, then restored in the same fashion. Samples were stored in 37 degrees C for at least 24 hours, then thermocycled from 5-55 degrees C 1000 times with a one-minute dwell time. Specimens were mounted in a Universal Testing Machine, and a chisel was applied to the restorations in compression mode at a crosshead speed of 5.0 mm/minute until bulk fracture of the amalgam occurred. The results indicated no difference in bulk fracture strengths between large amalgam restorations restored with and without Amalgambond Plus. However, small amalgam restorations restored with Amalgambond Plus exhibited significantly greater (p < 0.025) bulk fracture strengths than small amalgam restorations restored without use of the adhesive. PMID- 11203814 TI - Edge-bevel fracture resistance of three direct-filling materials. AB - Edge strength is defined in this study as the resistance to fracture of the beveled extension normally located at the cavosurface margin of a dental restoration. The edge strength of direct-filling alloy restorations plays an important role in maintaining the integrity of margins at tooth-alloy interfaces during functional loading. The purpose of this study was to determine the relative strength of an experimental consolidated silver material in comparison to other direct filling materials. The method used was designed as a simulation for relative edge-strength clinical properties. Stainless steel dies were formed from disks 5 mm thick, each with a centered hole tapered (1/48) toward the bottom side of the disk. A 41 degrees bevel, 0.5 mm wide as viewed from above, was placed on the top-side of the disk. Dispersalloy (D) or Unison (U) amalgam, Z-100 composite (C), hand-consolidated silver powder (HAg), or pneumatically consolidated silver powder (PAg) was used to fill the die opening. Excess was polished from both sides of the disk with 600-grit abrasive paper. The sample was loaded from the beveled side with a 3 mm-in-diameter flat-ended plunger at a rate of 1.0 mm/minute until failure. Failure load and total energy to failure were recorded and compared. Tukey's multiple comparison test (p < 0.05) ranked the materials (U) > (HAg) > (D) > (PAg) > (C) for fracture strength and (HAg) > (D) > (U) > (PAg) > (C) for fracture energy. PMID- 11203815 TI - The effect of depth of dentin demineralization on bond strengths and morphology of the hybrid layer. AB - Previous studies have shown that different phosphoric acid-based etchants do not penetrate intertubular dentin to the same depth. The purpose of this study was to determine the effect of different phosphoric acid-based conditioners on dentin shear bond strengths of three one-bottle bonding systems and to evaluate the corresponding interfacial ultramorphology. The null hypothesis to be tested was that no correlation could be established between the depth of intertubular demineralization and dentin shear bond strengths. The labial surface of 90 bovine incisors was polished to expose middle dentin. The specimens were randomly assigned to three one-bottle adhesive systems (n = 30): OptiBond SOLO, Permaquick PQ1, and Single Bond. For each adhesive system the specimens were divided into three subgroups of different silica-thickened etching gels (n = 10): 37.5% phosphoric acid gel (Kerr Gel Etchant), 35% phosphoric acid gel (Ultraetch), and 35% phosphoric acid gel (Scotchbond Etching Gel). After 24 hours in water at 37 degrees C, the specimens were thermocycled for 500 cycles in baths kept at 5 degrees C and 55 degrees C and the shear bond strengths measured. The data were analyzed with one-way and two-way ANOVA. Further, the adhesives were applied to 800 microns-thick bovine dentin disks (two per subgroup), which were restored with a low-viscosity composite resin. Six small dentin/resin sticks with a cross section of 1.0 mm x 1.0 mm were obtained from each bonded disk. They were then decalcified in a buffered solution of EDTA, fixed, stained, and sectioned in 90 nanometer-thick slices to observe under the Transmission Electron Microscope (TEM). The mean shear bond strengths were not statistically different at a confidence level of 95%. When the means were pooled for dentin adhesive and for etching gel, the number of cohesive failures was greater for Permaquick PQ1 and for Ultraetch, respectively. Pearson's correlation coefficient showed no correlation between hybrid layer thickness and bond strengths. The ultramorphological observation showed that all materials penetrated the dentin and formed a hybrid layer, regardless of the etching gel used. PMID- 11203816 TI - The influence of blood contamination on bond strengths between dentin and an adhesive resin cement. AB - The objective of this study was to determine in which step of adherent surface treatments blood contamination affects the bond strength between an adhesive resin and dentin. The coronal part of bovine incisors was polished flat to expose the dentin. The specimens were randomly divided into three groups and specific surface treatments were applied to each group: (1) a self-etching primer application (SP group); (2) 38% phosphoric acid etching followed by primer (non HC group); (3) acid etching followed by 10% sodium hypochlorite solution application and primer (HC group). The dentin surface was contaminated by human blood before or after either step of the surface treatments. The contaminated surfaces were washed with water after 30-second exposure and air-dried. A stainless-steel rod was adhered on the dentin surface with Panavia 21 after completing the surface treatment(s), and the tensile bond strength was measured. Fifteen subgroups including control groups were tested. If blood contamination occurred before collagen fibers were exposed by either phosphoric acid etching or self-etching primer application, the contamination presented almost no influence on bond strength. Blood contamination of the dentin surface where collagen fibers had been exposed decreased the bond strength. However, when the contaminated collagen fibers were dissolved or when the contamination occurred after the exposed collagen fibers were dissolved, the bond strength was maintained. The bond strength was markedly decreased when the contamination occurred after the primer application (Scheffe's Comparison, SP group: p = 0.0003, non-HC group: p < 0.0001), but was restored by reapplication of the self-etching primer. This study revealed that the effects of blood contamination on the bond strength of adhesive resin to dentin vary greatly depending on the adherent surface conditions. PMID- 11203817 TI - Effect of food-simulating liquids on the flexural strength of composite and polyacid-modified composite restoratives. AB - This study investigates the effects of food-simulating liquids on composite and polyacid-modified composite restoratives. Three composite (Z100, Spectrum TPH, and Tetric Ceram) and three polyacid-modified composite (F2000, Dyract AP, and Compoglass) restoratives from the same manufacturers were selected for the study. Flexural strength specimens (25 x 2 x 2 mm) based on ISO 4049 specifications were fabricated according to the manufacturers recommendations. After light polymerization, the specimens were removed from their molds and conditioned for one week at 37 degrees C in the following mediums: (1) deionized water, (2) 0.02 M citric acid, (3) heptane, and (4) 50% ethanol-water solution. Specimens stored in air were used as controls. The sample size was five for each material-medium combination. After conditioning, the specimens were blotted dry, measured, and subjected to flexural strength testing using an Instron Universal Testing Machine with a crosshead speed of 0.05 mm/minute. With the exception of Compoglass, flexural strength of all restoratives after conditioning in heptane was significantly greater than that after conditioning in all other mediums and the control. Although no significant difference in flexural strength values was observed between the different restoratives when the materials were conditioned in heptane or air (control), significant differences were observed between the different restoratives after conditioning in aqueous solutions (water, citric acid, and ethanol-water solution). The flexural strengths of the composites were generally significantly higher than their polyacid-modified counterparts after conditioning in the various aqueous solutions. The detrimental effects of aqueous solutions on flexural strength appeared to be greater with polyacid-modified composite resins than with composite restoratives. PMID- 11203818 TI - Repair strength of etched vs silica-coated metal-ceramic and all-ceramic restorations. AB - The purpose of this in vitro study was to examine shear bond strengths of composite resin to metal-exposed porcelain-fused-to-metal (PFM) and all-ceramic restorations after silica coating or etching with 5% hydrofluoric acid (HF). Specimens were fabricated for each of the following groups: two all-ceramic materials [a feldspathic porcelain (Vita Mark II) and a leucite-reinforced glass ceramic (IPS Empress)], and one noble metal-ceramic (Orplid Keramik I alloy; Vita VMK 68 N felspathic veneer ceramic). These groups were repaired with resin composites after different pretreatment methods. In one metal-ceramic subgroup the surface exhibited a 50% metal and 50% ceramic exposure. In the silica-coating groups, the specimen surfaces were air abraded with silica acid-modified Al2O3 (CoJet Sand) and treated corresponding to the porcelain repair with resin composite. For control groups, the surfaces were etched with 5% HF for 60 seconds and treated in the same way as the silica-coated groups. After 24 hours of storage (distilled water, 37 degrees C) and an additional 24 hours of thermocycling (1150 x 5 degrees C/55 degrees C) the specimens were debonded using a shear bond strength test (n = 15). In all groups the silica coat repair achieved equal or significantly higher bond strengths than did the etching technique (p < 0.05, Mann-Whitney U test). In the metal-exposed group, the mean bond strength increased from 7.3 MPa to 16.3 MPa following the silica-coat repair. Results indicated that silica coating represents a suitable treatment for the intraoral repair of the materials tested in the present study. PMID- 11203819 TI - Factors affecting shear bond strength of composite resin to fluorosed human enamel. AB - The aim of this work was to determine the effects of age, severity of fluorosis, and etching time on the shear bond strength of direct composite resin to human enamel. A total of 117 teeth, freshly extracted from patients in areas of Saudi Arabia endemic for dental fluorosis, were classified according to age (< 40 years and 40+ years) and severity of fluorosis, using the Thylstrup and Fejerskov index, TFI: TFI = 0, TFI = 1-3, and TFI = 4-6. Cylindrical composite resin specimens 5 mm in diameter and 3 mm high were bonded to the flattened midlabial enamel surfaces etched for 60 or 120 seconds and shear bond strength measured, using the Instron Universal Testing Machine at a crosshead speed of 0.5 mm/minute. Shear bond strength of the resin varied between 11.2 +/- 3.6 and 21.6 +/- 4.1 MPa. Three-way analysis of variance and Sheffe's multiple range test showed that the severity of fluorosis had no statistically significant effect on shear bond strength (p > 0.05). However, the bond was significantly stronger in teeth from patients < 40 years old than from those 40+ years old. Furthermore, at age < 40 years, shear bond strength was significantly higher in teeth etched for 120 seconds than those etched for 60 seconds (p < 0.05), but this was not the case in teeth from the older patients. In teeth with TFI = 1-3, the mode of bond failure was predominantly mixed, but at TFI = 4-6, the bond failure was mostly cohesive in enamel at all ages and etching times. It is, therefore, concluded that both age and etching time affect the shear bond strength of composite resin to fluorosed human enamel. PMID- 11203820 TI - Rigidity and retention of ceramic root canal posts. AB - Ceramic root-canal posts offer potential advantages over other types with respect to aesthetics and biocompatibility. Any post must be sufficiently rigid and retentive to withstand functional forces. Ceraposts (1.2 mm coronal diameter, ceramic, tapering, smooth posts) and Paraposts (1.25 mm, stainless-steel, parallel, serrated posts) were tested for rigidity by means of a three-point bending test. To test retention in roots, ceramic posts were cemented using one of three protocols: (1) glass-ionomer cement, (2) silane coupling agent and resin cement, or (3) sandblasted post surface, silane coupling agent, and resin cement. Stainless-steel posts were cemented with resin. The tensile force required to dislodge the posts, following four weeks of storage in water, was recorded. Data were compared using Student's t-test and Mann-Whitney U analysis. Ceraposts were significantly more rigid than Paraposts (p < 0.001). Paraposts cemented with resin were significantly more strongly retained than Ceraposts following any cementation protocol (p < 0.001). Retention of the ceramic posts was significantly greater with a silane coupling agent and resin cement than with glass-ionomer cement (p < 0.001). Sandblasting the ceramic posts produced variable results and needs further investigation before it could be recommended. PMID- 11203821 TI - Marginal hybrid layer in Class V restorations. AB - The aim of this study was to evaluate the morphology of the hybrid layer (identified as marginal hybrid layer) along the cervical margins of Class V restorations using several bonding systems. Class V restorations were prepared in vitro at the CEJ in extracted third molars. Three different bonding systems were selected: Scotchbond 1 (Single Bond), Scotchbond MP, and Clearfil Liner Bond 2V. After finishing each restoration with disks, each margin was polished for one minute with polishing paste. The margins of half of the restorations were then treated with 10% phosphoric acid for five seconds, washed in deionized water, and then stored in water for 24 hours before SEM analysis. The margins of the other half of the restorations were treated with 10% phosphoric acid for five seconds, then with 1.5% NaOCl gel for two minutes to remove noninfiltrated collagen, then washed and stored in water for 24 hours. Each sample was gold coated and observed under SEM. A one-way ANOVA was performed to determine if there were any statistically significant differences in hybrid layer thicknesses. The thickness of the marginal hybrid layer measured under SEM was 1.5-2.5 microns thick in Scotchbond MP and Scotchbond 1 but varied from 0.0 to 12.0 microns in Clearfil Liner Bond 2V when observed after NaOCl postpolishing procedures. Far more porosities were seen in the marginal hybrid layer of Clearfil Liner Bond 2V. Enamel margins were free from a hybrid layer in both groups. This study demonstrated that collagen fibrils are not completely infiltrated by adhesive resin at the CEJ level along the cavorsurface margin of the restorations. The presence of noninfiltrated collagen along the external margins may reduce the sealing capability of bonding systems, leaving many open spaces and gaps, which may jeopardize the durability of the bond over time. PMID- 11203822 TI - Techniques in recording centric relation. AB - 1. Muscle seated centric registration is a reproducible method of obtaining centric relation (Wood, 1994). 2. The muscle-seated CR record provides a consistent, accurate, less technique-sensitive CR record of condylar position. PMID- 11203823 TI - Expedited custom post and core technique. PMID- 11203824 TI - Conservative anterior tooth replacement using fiber-reinforced composite. PMID- 11203825 TI - Academy of operative dentistry. Award of Excellence. Dr Bruce Brownfield Smith. PMID- 11203826 TI - Academy of Operative Dentistry. Hollenback Memorial Prize. Dr Frederick C Eichmiller. PMID- 11203828 TI - Class II restorations with a polyacid-modified composite resin in primary molars placed in a dental practice: results of a two-year clinical evaluation. AB - This study evaluated the two-year success rate of a hybrid composite material (TPH-Spectrum; Dentsply DeTrey, Konstanz, Germany) and a polyacid-modified composite resin (Compoglass, Vivadent, Schaan, Liechtenstein) in Class II restorations placed in primary molars in a dental practice. In each of 52 children, at least two primary molars were restored. Ninety-six primary molars were filled with TPH-Spectrum using the total-etching technique, and 94 with Compoglass without acid etching prior to application of the bonding adhesive. At baseline, one and two years, the restorations were assessed according to the Ryge criteria. Forty-seven children with a total of 132 fillings (68 TPH-Spectrum, 64 Compoglass) were evaluated after two years. The cumulative success rate after 24 months amounted to 89.2% for the Compoglass and 89.7% for the TPH-Spectrum restorations. No significant differences were observed between the two materials with respect to color matching, cavosurface discoloration, anatomic form, margin integrity and caries assessment. This investigation suggests that for a period of two years, the hybrid composite TPH-Spectrum and the polyacid-modified composite resin Compoglass, are suitable materials for restoration of primary molars. PMID- 11203827 TI - Tooth-colored filling materials for the restoration of cervical lesions: a 24 month follow-up study. AB - The recently developed resin-modified glass ionomer cements and the polyacid modified composites are promising alternatives to conventional materials for restoring cervical defects. This clinical study evaluated the clinical condition of cervical fillings 24 months following placement. The study subjects were 197 cervical restorations placed on incisors, canines and premolars in 37 patients for restoration of erosion/non-carious lesions (69 cases), primary carious lesions (57 cases) and the replacement of deficient restorations (71 cases). The teeth were randomly divided into four groups for restoration with either Tetric (composite, Group A: n = 36), Dyract (compomer, Group B: n = 79), Fuji II LC (resin-modified glass ionomer cement, Group C: n = 51) or Photac-Fil (resin modified glass ionomer cement, Group D: n = 31). The evaluation was done single blind at baseline, 8 and 24 months after the placement of the fillings, according to a modified USPHS rating scale. The assessment criteria were color stability, anatomical form, surface texture, marginal integrity, marginal discoloration and loss of filling. Statistical analysis was completed using Pearson chi-square and Fisher's exact test at a significance level of 5% (p < 0.05). After the 24-month period, the composite restorations showed superior results. The compomer fillings demonstrated conditions that were only slightly worse. A substantial number of the resin-modified glass-ionomer fillings were evaluated with bravo or even charlie scores in respect to at least one of the criteria assessed. PMID- 11203829 TI - Antibacterial activity of resin adhesives, glass ionomer and resin-modified glass ionomer cements and a compomer in contact with dentin caries samples. AB - A total of 103 clinical samples of carious dentin were used to study the antibacterial action of different dental resin adhesive materials (Gluma 2000, Syntac, Prisma Universal Bond 3, Scotchbond Multi-Purpose and Prime&Bond 2.0) glass ionomer cements (Ketac-Cem, Ketac-Bond, Ketac-Silver, Ketac-Fil) resin modified glass ionomer cements (Fuji II LC, Vitremer and Vitrebond) and a compomer (Dyract). The agar plate diffusion method was used for the microbial cultures and a chlorhexidine control. The growth of the caries-producing microorganisms was effectively inhibited by the Vitremer and Vitrebond cements, and to a lesser extent by the Scotchbond Multi-Purpose adhesive system. Overall, there were statistically significant differences in the antibacterial activity of the products tested. PMID- 11203830 TI - The use of resin composite pins to improve retention of Class IV resin composite restorations. AB - This study evaluated the effect of an intracoronal resin composite pin on Class IV resin composite restorations. A control group of 16 bovine teeth was prepared with standardized conventional Class IV preparations. For an experimental group, 16 similar Class IV preparations were made, with the addition of an intracoronal pin channel prepared with a #330 bur into the dentin. All specimens were restored with Herculite XRV and OptiBond according to the manufacturer's recommendations. After one week, specimens were placed in an Instron Universal Testing Machine and loaded at 90 degrees to the long axis until the restorations failed. Results indicated that the mean fracture load of the Class IV restoration group, with the resin composite pin, was 36% higher than the conventional Class IV group (p = 0.02). An intracoronal resin composite pin may aid the retention and resistance form of complex resin composite restorations. PMID- 11203831 TI - Effect of sealant viscosity on the penetration of resin into etched human enamel. AB - This study was designed to investigate the relationship between the etched depth, penetration of sealants and marginal seal. Sixty unerupted lower first premolars extracted from patients for orthodontic reasons were thoroughly cleaned and stored in an antiseptic Ringer's solution at 4 degrees C. A "window" on the occlusal of 15 of the premolars, including both mesial and distal pits, was developed by painting nail varnish around the border of the occlusal surfaces. Etching was then done with 35% phosphoric acid for 60 seconds to all 60 premolars. Five of the "window" teeth were evaluated by microradiography to determine the etched depth of the superficial and subsurface enamel. Five were prepared for SEM analysis to observe the change of the superficial etched enamel surface. Another five "window" teeth were embedded in epoxy resin and sectioned parallel to the long axis of the tooth through the fissures in order to observe the subsurface depth of the etch by SEM analysis. The other 45 teeth were divided into three groups of 15 teeth each. Fissures of each group of teeth were sealed using Prisma-Shield (LD Caulk), Concise White Sealant (3M Dental Products) or Teethmate A (Kuraray) sealants and stored in water (37 degrees C) for 24 hours. They were then sectioned and demineralized before being examined by a scanning electron microscope. Photographs of secondary electron image (SEI) were done to gradate the resin-infiltrated enamel and resin tags for these sealants. After SEM observation, the 15 samples of each applied sealant were polished to a high gloss again and placed in a silver nitrate solution for 24 hours before being examined under the SEM equipped with a back-scatter electron detector. Data were then analyzed using the Welch and Student t-tests. Results showed that fissured enamel of unerupted human lower first premolars became porous after etching with 35% phosphoric acid. The low viscosity sealant Teethmate A (approximately 260 mPa.s), penetrated fully and formed a resin-infiltrated layer in enamel beyond the etched depth. However, the high viscosity sealants (Prisma-Shield and Concise White Sealant) did not penetrate enough to ensure that the acid-etched enamel was infiltrated sufficiently by the sealant to insure good marginal seals. PMID- 11203832 TI - Bond strength of compomers to human enamel. AB - The study evaluated the tensile bond strength between human enamel and seven compomer restorative systems under different bonding conditions. Seven compomers were bonded to human tooth structure with and without phosphoric acid etching of the bonding surface, with and without the use of their recommended combined primer and bonding agent and with both moist and wet bond interface environments. Overall, the highest bond strengths to human enamel were attained using phosphoric acid conditioning, primers and moist bonding surfaces. PMID- 11203833 TI - Microleakage of light-cured resin and resin-modified glass-ionomer dentin bonding agents applied with co-cure vs pre-cure technique. AB - This in vitro study evaluated the effect of dentin bonding agents in reducing microleakage after three months in Class V restorations restored with Z100 resin composite. Materials tested were three types of resin-based dentin bonding agents: a multi-step (Scotchbond Multi-Purpose); a one-step (Scotchbond One Step); a self-etching, self-priming (Clearfil Liner Bond) and a resin-modified glass ionomer (GC Fuji Bond LC). Class V cavity preparations with occlusal margins in enamel and gingival margins in cementum were prepared both on labial and lingual surfaces of extracted premolar teeth. Restorations (two per tooth) were distributed randomly into nine test groups (n = 10) consisting of the various DBAs applied with co-cure and pre-cure techniques, and no dentin bonding as a negative control group. Samples were stored in saline for three months, thermocycled, stained with silver nitrate, then sectioned through the middle of the preparation to facilitate the removal of the composite resin restoration. For groups treated with the pre-cure technique, the differences between the enamel leakage values of SBMP-control, CFLB-control and SB1S-control subgroups were significant (p < 0.05). For enamel leakage values of groups treated with the co cure technique, the differences between the SBMP-control, SB1S-control, CFLB control and Fuji LC-control subgroups were significant (p < 0.05). For cementum leakage values of groups treated with pre-cure technique, the difference between the CFLB-control and the Fuji, SBMP and SB1S groups was significant (p < 0.05). No significant differences could be detected between the cementum leakage values of groups treated with the co-cure technique (p > 0.05). The differences between the values obtained with application of CFLB with the pre-cure and co-cure techniques at the cementum margins were found to be statistically significant (p = 0.02). No statistically significant differences could be detected between the pre-cure and co-cure values of the other test materials. Generally for every group, cementum microleakage values were greater than enamel microleakage values (p < 0.05). The use of Scotchbond Multi-Purpose, Scotchbond One-Step and Fuji Bond LC with the co-cure technique to decrease the application time did not cause any significant increase in microleakage. Only pre-curing using Clearfil Liner Bond provided better microleakage properties than the other pre-cured adhesives. PMID- 11203834 TI - Bond strengths of a porcelain material to different abutment substrates. AB - The study evaluated the bond strength values of a single-unit all-porcelain material luted with an adhesive-resin cement to different abutment substrates: amalgam, compomer, traditional glass ionomer cement, microhybrid resin composite, two resin composites for abutment build-up, gold, sandblasted gold, dentin and enamel. Syntac enamel-dentin bonding system, in combination with IPS-Empress porcelain material, was used. After thermal cycling, the samples were inserted into a Bencor jig device and sheared in a Controls testing machine. The statistical analysis of the differences between the bond strength values obtained was performed by ANOVA and the Student-Newman-Keuls multiple-comparison test. The type of failure at the interface was evaluated using scanning electron microscopy. The type of failure, such as adhesive, cohesive and adhesive cohesive, was correlated with bond strength values. Enamel, dentin and the two resin composites for crown build-up showed the highest bond strength values, while amalgam and gold samples showed the lowest. PMID- 11203835 TI - Flow characteristics and sealing ability of fissure sealants. AB - This study evaluated the relationship between fissure sealant viscosity, leakage prevention and the incidence of void formation of five commercially available pit and-fissure sealants. Seventy-two intact, caries free human pre-molars and molars were divided into six test groups of 12 teeth each. All teeth were cleaned with a flour of pumice prophylaxis followed by etching for 60 seconds with 37% H3PO4, rinsing for 30 seconds and drying with oil-free air. Five commercial, light-cured fissure sealants and an unfilled version of one sealant were applied following manufacturers' instructions. Teeth were thermal cycled for 5000 cycles from 5-50 degrees C with a one-minute dwell time at each temperature. Silver nitrate staining followed by mesiodistal sectioning was performed. Leakage and void formation were evaluated at X50 optical magnification. Viscosity was assessed by syringing the fissure sealants into short pipettes, allowing free flow for 30 seconds and then light curing for one minute. The length of unfilled capillary was measured with a Vernier gauge. All experimental data was subjected to a one way ANOVA, and where differences were detected, they were identified by a post hoc Tukey hsd test at a priori alpha = 0.05. Based on the conditions of the study, viscosity and flow characteristics had no effect on sealing ability or void formation. PMID- 11203836 TI - Three-dimensional optical profilometry analysis of surface states obtained after finishing sequences for three composite resins. AB - The operating protocols used for finishing composite resins are numerous and affect the success of filling from a mechanical, biological, and aesthetic point of view. The study determined the most favorable finishing for each of the composites considered. The three-dimensional optical profilometry examination was used to obtain qualitative and quantitative measurements of three hybrid composites. Tungsten carbide burs left irregularities harder to eliminate than those caused by diamond burs. Sof-Lex disks and the Enhance System gave good results for the three materials. Charisma presented a good surface regardless of polishing method used. Finishing Z100 and Prisma TPH required a special operating protocol as specified by the manufacturers. This study demonstrated that the finishing procedure for composite materials must be strictly followed to obtain optimal results. Profilometry proved to be an excellent method to study the surface roughness of samples. PMID- 11203837 TI - Microleakage of bonded amalgam restorations: effect of thermal cycling. AB - This study examined the effect of thermal cycling on the microleakage of bonded amalgam restorations. Three dental amalgam alloys and a gallium alloy were tested with two adhesive resin systems and copal varnish as a control. Class V cavity preparations were prepared on 168 freshly extracted premolars or molars. The preparations were placed parallel to and 1.0 mm occlusal to the cementoenamel junction (CEJ). Four groups of 42 teeth each were treated with one of the following adhesive dentin systems: Bond-It, All-Bond 2/Resinomer or a copal varnish (Copalite). The four groups of 42 teeth each were then restored with one of three dental amalgams: Orosphere Plus, Indiloy, Oralloy or a Gallium alloy (Galloy), resulting in 12 test groups of 14 teeth each. The specimens were stored in double distilled water at 37 degrees C for 24 hours. Final contouring and polishing of the restorations were performed under water spray. Half of the restorations in each group were thermocycled for 3000 cycles (5 degrees C-37 degrees C-55 degrees C-37 degrees C) with a dwell time of 15 sec at each temperature. The other half were stored in double distilled water at 37 degrees C for 24 hours. Then all 168 restorations were stained with dye, sectioned and scored for microleakage. Results showed that the adhesive dentin systems reduced microleakage in amalgam restorations compared to copal varnish only in non thermocycled specimens. Statistical analysis of the results showed that there was an extremely significant difference (p < 0.001) in microleakage between the non thermocycled and the thermocycled specimens in all test groups, whereas, there was no significant difference (p > 0.05) among thermocycled specimens. The reduction of microleakage was not significantly different between Bond-It and All Bond 2/Resinomer in non-thermocycled specimens. Oralloy showed the most microleakage in the non-thermocycled groups when compared to the other alloys using the same adhesive liner. PMID- 11203839 TI - Physical properties of three packable resin-composite restorative materials. AB - This study evaluated selected physical properties of three packable resin composites (Alert, SureFil and Solitaire) and compared them to two conventional hybrid materials (Prodigy and Z-100). The specific properties investigated were diametral tensile strength, transverse strength, elastic modulus and fracture toughness. Following photopolymerization, specimens for each composite material were stored in deionized water at 37 degrees C for 35 days. A one-way ANOVA and Tukey's post-hoc test were employed for each property to determine whether significant differences occurred with respect to specific restorative materials. All materials had statistically similar diametral tensile strengths. Alert had the highest mean fracture toughness and elastic modulus but had a low mean transverse-strength value. SureFil exhibited good mean physical property values compared to both the conventional and packable materials. Solitaire had low mean fracture toughness, transverse strength and elastic modulus values, which could cause concern regarding use in posterior restorations. The packable resin composites tested had a wide range of mean values for the physical properties investigated. Generally, Alert and SureFil were superior to Solitaire and comparable to the hybrid materials Prodigy and Z-100, but clear discrimination among performance of these materials requires clinical testing. PMID- 11203838 TI - Technique sensitivity of dentin bonding: effect of application mistakes on bond strength and marginal adaptation. AB - This in vitro study evaluated dentin bond strength and marginal adaptation of direct resin composites according to the manufacturers' instructions and with simulated application errors. One hundred and forty cavities were prepared into disks of freshly extracted human third molars and filled with one resin composite. Dentin adhesives of the third (with self-etching primer: Syntac Classic), fourth (with total etching: Scotchbond Multi-Purpose Plus) and fifth generation (one-bottle adhesive: Prime&Bond 2.1) were used for bonding. Simulated application mistakes were as follows: 1) prolonged etching; 2) excessive drying after conditioning; 3) drying primers immediately after application and 4) drying primers excessively. After 21 days of storage and 24 hours thermocycling (1150 cycles), replicas were made and push-out testing was performed. Replicas were examined for marginal adaptation using SEM (X200 magnification). Compared with values of the control groups, application errors resulted in dramatically decreased bond strengths and reduced percentages of gap-free margins for all products tested (p < 0.05). Excessive drying after conditioning exhibited significantly less effect for the third generation adhesive than for products requiring total etching/wet bonding. PMID- 11203840 TI - Cumulative assessment of factors leading to restorative decisions in an educational environment. A graphical demonstration using an in vitro case. AB - Even though accuracy and inter-examiner variation assessments of borderline restorative items have been previously reported, no attempt has been made to replicate the effect of cumulative, sequential diagnostic and treatment planning decisions. This study assesses the cumulative effect of factors indicating restorative needs by evaluating how readily tooth restoration was proposed on the basis of restoration quality and presence of caries (compared to gold standards). Ninety-one senior dental students in Mexico City (79% female; mean age 22.8 years) assembled in 19 teams of five students each. They sequentially evaluated 56 restored and unrestored posterior teeth in an in vitro model. Each student examined the set, removed those teeth needing restorative intervention and returned the remaining set for examination by a second student. When the second assessment was completed, the remaining teeth were turned over to the third teammate and so on. Teeth were subsequently assessed for restoration quality and enamel and dentinal caries. When a tooth showed a carious lesion, a dentinal lesion or a defective restoration, the likelihood of it being selected for restorative treatment increased. When more than one feature was present, the chances of the tooth being selected more frequently and earlier increased, accordingly. The specificity of restorative treatment needs was not excellent. A strong graphical association between the presence of caries and/or defects in restorations with proposed restorative treatment was demonstrated using a non quantitative research model. The more abundant these features were, the higher the probability appeared for a tooth to fit the clinical picture suitable for restorative intervention. PMID- 11203841 TI - Foreign body gingivitis associated with a new crown: EDX analysis and review of the literature. AB - Gingival inflammation associated with foreign bodies in connective tissue is termed Foreign Body Gingivitis (FBG). It is not commonly recognized by clinicians and has recently been described fully in the literature. It is more common in females, and the incidence by age follows a normal distribution, unlike bacterially-induced gingivitis. Most frequently, a red or red-and-white painful, chronic lesion, it has usually been present for less than one year and does not resolve with optimization of oral hygiene. It may be clinically confused with lichen planus. There is no gingival site predilection. Microscopically, foreign bodies are associated with the gingival inflammation, and elemental analysis suggests that they are usually derived from abrasives, and less commonly from restorative materials. Treatment of FBG is still unclear and its prevention is discussed. A case is presented in which a patient developed localized foreign body gingivitis after placement of a crown. Elemental analysis using energy dispersive X-ray microanalysis (EDX) of the foreign particles was most consistent with an abrasive material. PMID- 11203842 TI - Shade selection for composite repair of lost veneer facings. PMID- 11203843 TI - Buonocore Memorial Lecture. Adhesive dentistry in the 21st century. PMID- 11203844 TI - Clinical performance of Class II restorations in which resin composite is laminated over resin-modified glass-ionomer. AB - This study evaluated the one-year functioning of resin-composite/resin-modified glass-ionomer open-laminate restorations when used for restoring Class II cavities. It also investigated the effect of the thickness of the resin composite layer on the performance of such restorations. The test restorations were made of Vitremer glass ionomer, Scotchbond Multipurpose Plus and Z100 resin composite, and the control restorations were made of Z100 with Scotchbond Multipurpose Plus. Forty pairs of restorations were placed in 40 patients aged 16 years and over. The thickness of the resin composite layer was measured both clinically and in the laboratory using a reflex microscope. The completed restorations were assessed in vivo and in vitro at baseline, six-month and one-year recalls using a modified Ryge system. The reflex microscope measurements showed that the majority of restorations had a resin composite layer of more than 1.5 mm in thickness, as intended. At one year, 37 pairs of restorations were examined. Apart from a few minor problems, all performed satisfactorily. Thus, it appears that the resin composite/resin modified glass ionomer open laminate is a suitable technique for restoring Class II cavities. PMID- 11203845 TI - Review of bonded amalgam restorations, and assessment in a general practice over five years. AB - This study reviewed the literature on bonded amalgam restorations and assessed the failure, marginal fracture and marginal staining behavior of 366 Permite C amalgam restorations lined with five dentin bonding resins (Scotchbond 2, Panavia Ex, Amalgambond, Amalgambond Plus, Geristore) and a polyamide cavity varnish (Barrier). The restorations were placed in the posterior permanent teeth of 190 adult patients and examined at intervals over periods of up to five years. There were five restoration failures (1.4%), usually from tooth fracture, involving Class II preparations in molar teeth. No instances of persistent pulpal sensitivity or recurrent caries were reported. The marginal deterioration of the restorations was assessed indirectly using photographs for comparison with two standard sets of enlarged color transparencies. Most of the marginal fracture and marginal staining scores were low, with little difference between the six lining materials at any period. PMID- 11203846 TI - Cervical compomer restorations: the role of cavity etching in a 48-month clinical evaluation. AB - Compomers are defined as polyacid-modified resin composites. They are supposed to combine the advantages of traditional glass-ionomer cements with resin composites. This study clinically evaluated a compomer in cervical cavities. Sixty cervical cavities in premolars and molars (24 with cervical caries and 36 with abrasions) randomly divided into two groups of 30 teeth (Group 1 and Group 2) were restored with Dyract (DeTrey-Dentsply, York, PA 17405-0872). The cavities of Group 2 were etched for 30 seconds with orthophosphoric acid before compomer application, while the Group 1 cavities received no treatment. All the restorations were evaluated every six months, up to 48 months: characteristics assessed according to USPHS-modified standards were retention, secondary caries, post-operative sensitivity, marginal adaptation and discoloration, color and wear. The Kaplan-Meier's survival analysis was performed. In both groups, retention was high without any statistically significant difference. No difference was found between the two groups for caries, post-operative sensitivity and wear--that all had a low incidence. Color was not perfectly matched, however, there was no statistically significant difference between the two groups. Marginal discoloration and marginal adaptation loss were significantly higher in non-etched group (p < 0.05). Clinically relevant failure required 17.2% of restorations in the non-etched group and 10% in the etched group to be replaced: this difference was not statistically significant. Dyract has an acceptable clinical behavior when used in cervical cavities. Its marginal adaptation is enhanced by etching. PMID- 11203847 TI - Fracture resistance of five pin-retained core build-up materials on teeth with and without extracoronal preparation. AB - Core build-ups should provide satisfactory strength and resistance to fracture both before and after crown preparation. This paper examines the resistance to fracture of core build-ups in different materials and the fracture resistance of core build-ups when these have been reduced for full crown preparation. Standardized core build-ups were made on groups of extracted molar teeth of similar size, with 10 teeth per group. Three resin-composite (prisma APH: Dentsply, Weybridge, UK; Ti-Core, Essential Dental Systems, NJ, US and Coradent, Vivadent, Liechtenstein), one cermet (Ketac-Silver, ESPE GmbH, Seefeld, Germany) and one amalgam material (Duralloy, Degussa Ltd, Cheshire, UK). These specimens were subjected to compressive force on a universal testing machine and the force at fracture noted. Standardized full crown preparations were made on a further five groups of core build-up specimens using the same materials as above. These prepared specimens were subjected to compressive force on a universal testing machine and the force to fracture noted. The results indicated that amalgam core build-ups demonstrated higher fracture resistance than the other materials examined. There was a general decrease in the fracture strength of the specimens following crown preparation, with the teeth restored with the amalgam core build ups showing a greater percentage reduction in fracture strength than the other materials tested. Prepared core build-ups in a hybrid composite material provided the highest fracture resistance. The cermet material used provided the lowest resistance to fracture in both the core build-up and crown preparation specimens. In terms of fracture resistance, no advantage was apparent in using the two composite materials designated as being specifically appropriate for core build ups. PMID- 11203848 TI - Influence of dentin conditioning and contamination on the marginal integrity of sandwich Class II restorations. AB - This study investigated the influence of dentin conditioning and contamination on the marginal adaptation of Class II sandwich restorations. Large butt-joint MOD cavities with cervical margins located 1 mm below the CEJ were cut into 72 extracted human molars. Nine groups were filled using a total-bond technique with Z100 or a sandwich technique with either Vitremer or F2000 in combination with Z100. For all three material combinations three different pretreatments were compared: total etch, selective etch and dentin contamination with saliva and blood prior to primer/adhesive application. After water storage for 21 days and thermocycling (2000x, 5-55 degrees C) replicas were produced for quantitative marginal analysis in the SEM. Teeth were immersed in 0.5% basic fuchsin for 24 hours and dried. Percent dye penetration over the total marginal length was analyzed in three layers using a sequential grinding technique. Statistical analysis was performed using a two-way ANOVA. Post-hoc analyses were carried out with univariate Mann-Whitney-U-tests adjusting for multiple comparisons by a sequentially rejective test procedure (Bonferroni-Holm) at p < 0.05. Both F2000 and Vitremer sandwich restorations showed better marginal adaptation than Z100 total-bond restorations with all pretreatments. Acid etching of the dentin significantly influenced the marginal adaptation of Z100 total-bond restorations and Vitremer sandwich restorations. All types of restorations showed considerable microleakage. On contaminated dentin, sandwich restorations showed better marginal integrity than total-bond restorations. Marginal adaptation did not correspond with microleakage in all groups. In conclusion, F2000/Z100 and Vitremer/Z100 sandwich restorations show better marginal adaptation than Z100 total-bond restorations in large Class II cavities with cervical margins in dentin. Microleakage cannot predictably be prevented with the sandwich technique. Sandwich restorations seem to be less sensitive to contamination with saliva and blood. PMID- 11203849 TI - Bonded amalgam restorations: using a glass-ionomer as an adhesive liner. AB - Due to the lack of adhesiveness of amalgam to tooth structure, several adhesive cements have been utilized in bonded amalgam restorations. This study evaluated whether Fuji-II glass-ionomer cement is an appropriate adhesive liner in bonded amalgam restorations. Two adhesive composite luting cements (Amalgambond Plus and Panavia-21) and Copalite cavity liner were compared. The study was conducted in two phases. In the first part, we quantitatively assessed the tensile bond strengths as well as the failure modes of amalgam bonded to human dentin, using different adhesive liners. In each group, the flat dentin surface was treated with the assigned adhesive cement with a Teflon mold, followed by condensation of amalgam (Valiant PhD) onto it. Each group's mean tensile bond strengths were recorded and the statistical analysis by one way ANOVA showed no significant differences among groups (p > 0.05). Similar to the fracture patterns of the Amalgambond Plus and Panavia-21 groups, the failure mode of Fuji-II group was predominantly adhesive fracture. In the second part, the fracture strengths of amalgam restored teeth were measured using different adhesive liners. Standard MOD cavities were prepared in each tooth except for the intact tooth group. After treatment with the assigned adhesives or varnish, the cavities were restored with amalgam. Fracture strengths were then measured and the fractured interfaces examined using a scanning electron microscope. The fracture strengths of the intact tooth, Amalgambond Plus, Panavia-21 and Fuji-II groups were significantly higher than those of the Copalite and prepared cavity without restoration groups (p < 0.01). Accordingly, Fuji-II glass-ionomer cement, when used as an adhesive liner of amalgam restoration, may effectively reinforce the remaining tooth structure and, therefore, enhance the fracture resistance of the amalgam-restored teeth. PMID- 11203850 TI - In vivo examination of the Scotchbond Multi-Purpose Dental Adhesive System in rat (vitalmicroscopic study). AB - No data are available on the direct acute vascular effect of dental bonding materials on the dental pulp. This study investigated the effects of the components of a composite resin-bonding system on pulpal vascular diameter. Three groups of 10 male Sprague-Dawley rats (weighing 330 +/- 51 g) were used for this investigation. The first lower incisor of the rats was prepared for vitalmicroscopy. Changes in vessel diameter were recorded prior to, and at 5, 15, 30 and 60 minutes after the bonding agents (with/without etching) or saline (control) were administered on dentin as recommended by the manufacturer. In control rats, the vessel diameter was elevated slightly (2.96 +/- 4.08%) during the whole experiment. However, in the presence of bonding materials, an enhancement of 12.58 +/- 7.1% without etching and 13.11 +/- 8.6% with acid etching was registered as the increase in vascular diameter. There were significant (p < 0.05) differences between the control group and those treated with bonding agent components. Results suggested that resin composite bonding agents applied to a thin layer of dentin have an acute vasodilating effect on the dental pulp. The clinical significance of this vascular alteration in the dental pulp requires further study. PMID- 11203851 TI - Resistance to condensation of 'condensable' resin composites as evaluated by a mechanical test. AB - This study compared the resistance-to-condensation forces of recently introduced condensable resin composites to that of amalgams and conventional resin composites. Using the flat platens of a servohydraulic testing machine, cylindrical specimens of each material 2.8 mm in diameter and 5.5 mm in length were compressed diametrally over two seconds to a thickness of 0.75 mm. Peak forces generated during compression were recorded. This method ranked the various classes of restorative material for resistance to condensation in the same order as most clinicians subjectively reported, with the highest forces observed with admixed dental amalgams, followed in order by spherical amalgams, condensable resin composites and conventional resin composites. Although peak forces observed with the condensable resin composites were generally higher than those observed with conventional resin composites, these were significantly lower than the peak forces observed with amalgams. PMID- 11203852 TI - Metal surface treatment: characterization and effect on composite-to-metal bond strength. AB - This study evaluated the effect of four methods of metal surface preparation and the use of silane on the bond strength between resin and a Noble metal alloy. SEM Examination and x-ray energy-dispersive spectroscopy (EDS) of the various metal surface treatments was also performed. One-hundred metal disks were cast in a Noble metal alloy (Porcelain #76). Ninety disks were polished flat and the surfaces received one of four abrasive treatments (n = 20). 1) Roughening with a diamond bur at high speed; 2) Air abrasion with an intraoral sandblaster using alumina particles; 3) Air abrasion with KCP-2000 and 4) Air abrasion with an intraoral sandblaster using silanated silica covered alumina particles (CoJet Sand). Half the specimens from each treatment group (n = 10) were silanated prior to bonding procedures (All-Bond 2 adhesive system, Pertac-Hybrid composite). Specimens were stored in distilled water at 37 degrees C and thermocycled prior to shear strength testing. The 10 remaining metal disks were used for scanning electron microscopy and x-ray energy-dispersive spectroscopy (EDS). Scanning electron microscopy examined the micromorphology of the metal surfaces produced by the four abrasive treatments and x-ray energy-dispersive spectroscopy (EDS) to evaluate changes in surface composition. Two untreated disks served as controls. One-way ANOVA and Tukey's HSD post-hoc test demonstrated that air abrasion with CoJet-Sand and silane resulted in significantly higher resin-to-metal bond strength than all other metal surface treatments, while roughening with a diamond bur produced the lowest bond strength. Resin-to-metal bond strength was similar for all other particle abrasive treatments with or without silane. Using silane significantly improved bond strength only for metal surfaces treated with CoJet Sand. An increase in Al concentration was observed on metal surfaces sandblasted with aluminum oxide, and an increase in the concentration of both Al and Si was observed on surfaces air-abraded with CoJet-Sand. PMID- 11203853 TI - Solubility and sorption of resin-based luting cements. AB - This study compared the seven-day water sorption, water solubility and lactic acid solubility of three composite cements and three resin-modified glass-ionomer cements. Disc-shaped specimens measuring 15 mm x 0.5 mm were prepared according to each manufacturer's specifications and desiccated to a constant mass. Specimens were then placed in distilled water at 37 degrees C for seven days. Acid solubility was performed in 0.01 M lactic acid. The weight changes of the specimens after immersion in distilled water or 0.01 M lactic acid were measured using an electronic analytical balance. A one-way ANOVA followed by the Ryan Einot-Gabriel-Welsch (REGW) multiple range test was performed on all data. Significant differences (p < 0.05) were found among several cements tested for each of the properties investigated. Due to their hydrophilic nature, all resin modified glass-ionomer cements showed significantly higher water sorption compared to composite cements. PMID- 11203854 TI - Post retention and post/core shear bond strength of four post systems. AB - As clinicians we continue to search for a post system which will give us maximum retention while maximizing resistance to root fracture. The introduction of several new post systems, with claims of high retentive and resistance to root fracture values, require that independent studies be performed to evaluate these claims. This study tested the tensile and shear dislodgment forces of four post designs that were luted into roots 10 mm apical of the CEJ. The Para Post Plus (P1) is a parallel-sided, passive design; the Para Post XT (P2) is a combination active/passive design; the Flexi-Post (F1) and the Flexi-Flange (F2) are active post designs. All systems tested were stainless steel. This study compared the test results of the four post designs for tensile and shear dislodgment. All mounted samples were loaded in tension until failure occurred. The tensile load was applied parallel to the long axis of the root, while the shear load was applied at 450 to the long axis of the root. The Flexi-Post (F1) was significantly different from the other three in the tensile test, however, the Para Post XT (P2) was significantly different to the other three in the shear test and had a better probability for survival in the Kaplan-Meier survival function test. Based on the results of this study, our recommendation is for the Para Post XT (P2). PMID- 11203855 TI - Effect of three surface sealants on marginal sealing of Class V composite resin restorations. AB - This study evaluated in vitro the effectiveness of three different surface sealants (Fortify, Protect-it! and Optiguard) on the marginal sealing of Class V light-activated composite resin restorations (Prodigy). For this purpose, 20 sound noncarious human premolars extracted within a six-month period were selected. Class V cavities with the occlusal margin in enamel and cervical margin in cementum were prepared in both buccal and lingual surfaces. The teeth, randomly assigned in four groups with 10 cavities in each group, were restored with composite resin after applying an adhesive system (Optibond FL). After the finishing and polishing procedures, the restorations were covered with a specific surface sealant, except for the control samples, which were not sealed. After placing restorations, the specimens were thermocycled and immersed in a 50% silver nitrate solution (tracer agent) for eight hours, sectioned longitudinally and analyzed for leakage using an optical microscope in a blind study with three examiners. The marginal microleakage was evaluated at the occlusal and cervical interfaces and compared among the four groups using the Kruskall-Wallis and the Wilcoxon Tests. There was better sealing at the occlusal margin, and in this region, there were no statistically significant differences among the materials (p > 0.05). In the cervical region, Fortify and Protect-it! showed improved results over the Control Group, and Optiguard showed similar results to the Control Group (without sealing). PMID- 11203856 TI - Operative dentistry: the first twenty-five years. PMID- 11203857 TI - Leucite-reinforced glass ceramic inlays and onlays after six years: clinical behavior. AB - Ceramic inlays are an esthetic substitute for large amalgam and other metallic restorations. This controlled clinical study evaluated the performance of IPS Empress inlays and onlays with cuspal replacements and proximal margins below the cementoenamel junction over six years of clinical service. Six dentists placed 96 ceramic restorations in 34 patients. Luting was accomplished using the enamel etch-technique, a dentin bonding system (Syntac Classic) and four different composite systems. The restorations were assessed by two calibrated investigators using modified USPHS criteria at baseline (96 restorations), one (96), two (95), four (89) and six years (67). Seven of the 96 restorations investigated had to be replaced (failure rate 7%; Kaplan-Meier): Five inlays suffered cohesive bulk fractures and two teeth required endodontic treatment. After six years of clinical service, significant deterioration (Friedman 2-way ANOVA; p < 0.05) was found for marginal adaptation of the remaining restorations. Ninety-four percent of the surviving restorations exhibited marginal deficiencies, independent of the luting composite. Neither the absence of enamel margins, nor cuspal replacement significantly affected the quality of the restorations. PMID- 11203858 TI - Leucite-reinforced glass ceramic inlays after six years: wear of luting composites. AB - Wear of luting composites is still an unsolved problem with adhesive inlays. However, only limited clinical research has been conducted regarding this phenomenon. This study evaluated the substance loss within the luting gap over a six-year period in vivo. In the course of a controlled prospective clinical study, 16 patients received 39 Class-II IPS Empress inlays. Variolink Low (Vivadent; n = 18) was used as conventional low-viscosity luting composite, the hybrid-type restorative resin composite Tetric (n = 21; Vivadent) was applied according to the ultrasonic insertion technique. The restorations were clinically assessed after 6, 12, 24, 36, 48 and 72 months and replicas were made. The contact-free occlusal areas of the replicas were scanned by use of a computer controlled profilometer (Perthen S3P), the analysis of the data was computed using a newly developed software (Xpert for Windows 95) and statistically analyzed with non-parametric tests. After six months all restorations exhibited marginal ditching. The percentage of detectable luting gap abrasion increased between each recall appointment (32% after six months, 48% after 12 months, 46% after 24 months, 55% after 36 months, 59% after 48 months and 65% after 72 months). Except for the 48-months results, no significant difference between the materials used for luting was evident (p > 0.05). Between the width and the depth of the luting space a linear regression was computed. The quantitative evaluation clearly demonstrated that hopes of relevantly reduced wear of luting composites were not confirmed when using the higher filled luting material. PMID- 11203859 TI - Eight-year clinical evaluation of fired ceramic inlays. AB - This study evaluated the quality of fired ceramic inlay restorations consisting of a feldspathic porcelain system (G-Cera Cosmotech II, GC Co, Tokyo, Japan) after eight years in vivo. Forty-five fired ceramic inlays (for 26 premolars and 19 molars; Class I in 12 teeth, Class II in 31 teeth and onlay in two teeth) were placed in 25 patients. All restorations were evaluated at the time of placement and at 6 months, 1, 2, 4, 6 and 8 years after placement using modified USPHS criteria. Replicas of the restorations were observed with a scanning electron microscope (SEM) to evaluate the degradation of the marginal area and wear loss of the restoration. Longevity was observed in 80% of the fired ceramic inlay restorations at eight years (Kaplan-Meier method), although it was 92% at the six year observation. Marginal fracture was detected in 11 restorations (22%), including bulk fracture in five (11%), which had first occurred during the last two years. Recurrent caries was observed in three (7%) cases and marginal discoloration in 14 (31%). SEM evaluation disclosed marginal microfractures in 77% of the restorations, wear in 36% and wear of the resin cement along the margin in 74% at eight years. No significant difference was observed in each of these three characteristics between molars and premolars. This longitudinal eight year clinical observation suggested that fired ceramic inlay restorations made by the G-Cera Cosmotech II system are clinically acceptable. However, critical failure as bulk fracture may become a future problem since marginal disintegration was detected in 77% of the restorations from microscopic and macroscopic perspectives. PMID- 11203861 TI - Marginal seal of resin-modified glass ionomers and compomers: effect of delaying polishing procedure after one-day storage. AB - This study evaluated the effects of polishing after one-day storage in water on the marginal gap formation around fillings using three resin-modified glass ionomers, one compomer, one conventional glass ionomer, and one micro-filled composite as a control. The study also examined the marginal gap and bond strength in Teflon cavities and the flexural strength of these restorative materials, which may influence the marginal gap formation. Immediately after the setting procedure, the specimen was polished and a marginal gap of approximately 10-25 micrometers was observed regardless of the type of restorative material used. In contrast, we observed no gap or a 1-2 micrometer gap width when the specimens were polished after one-day storage. Only Dyract did not show this pattern. Statistical difference was observed between immediately polishing and polishing after one-day storage in all materials except Dyract. Hygroscopic expansion, bond strength and flexural strength play important roles in reducing the marginal gap in tooth cavities filled with two types of glass-ionomer restorative materials. In contract, these properties did not play important roles in reducing the marginal gap width for Dyract. PMID- 11203860 TI - Brushing abrasion of luting cements under neutral and acidic conditions. AB - Four resin based materials (Compolute Aplicap, ESPE; Variolink Ultra, Vivadent; C&B Metabond, Parkell and Panavia 21, Kuraray), two carboxylate cements (Poly-F Plus, Dentsply DeTrey and Durelon Maxicap, ESPE), two glass-ionomer cements (Fuji I, GC and Ketac-Cem Aplicap, ESPE), one resin-modified glass ionomer cement (Vitremer, 3M) one polyacid-modified resin composite (Dyract Cem, Dentsply DeTrey) and one zinc phosphate cement (Harvard, Richter & Hoffmann) were investigated according to their brushing resistance after storage in neutral and acidic buffer solutions. For this purpose 24 cylindrical acrylic molds were each filled with the materials. After hardening, the samples were stored for seven days in 100% relative humidity and at 37 degrees C. Subsequently, they were ground flat and polished. Then each specimen was covered with an adhesive tape leaving a 4 mm wide window on the cement surface. Twelve samples of each material were stored for 24 hours in a buffer solution with a pH of 6.8. The remaining 12 samples were placed in a buffer with a pH of 3.0. All specimens were then subjected to a three media brushing abrasion (2,000 strokes) in an automatic brushing machine. Storage and brushing were performed three times. After 6,000 brushing strokes per specimen, the tape was removed. Brushing abrasion was measured with a computerized laser profilometer and statistically analyzed with ANOVA and Tukey's Standardized Range Test (p < or = 0.05). The highest brushing abrasion was found for the two carboxylate cements. The lowest brushing abrasion was found for one resin based material, Compolute Aplicap. With the exception of three resin-based materials, a lower pH led to a higher brushing abrasion. PMID- 11203862 TI - Effect of dentin deproteinization on microleakage of Class V composite restorations. AB - The role of the collagen fibers in dentin adhesion has not clearly been established. Therefore, this laboratory study evaluated the microleakage at resin dentin and resin-enamel interfaces of Class V composite restorations after etching enamel and dentin with phosphoric acid (H3PO4) or after etching with H3PO4 followed by deproteinization with 5% sodium hypochlorite (NaOCl) to prevent the formation of a hybrid layer. Ten extracted human molars were used to prepare standardized Class V cavities on both buccal and lingual surfaces. The teeth were randomly divided in two groups: 1) Class V cavities that were etched with H3PO4 for 15 seconds; b) Class V cavities that were etched with H3PO4 for 15 seconds followed by collagen removal with 5% NaOCl for two minutes. The cavities were restored using the Prime & Bond 2.1 bonding system and TPH resin composite. The specimens were stored in water for 24 hours at 37 degrees C and thermocycled 500 times between water baths kept at 5 degrees C and 55 degrees C. After thermocycling, specimens were immersed in a 0.5% aqueous solution of basic fuchsin for 24 hours. Three longitudinal sections of each restoration were obtained and examined with a stereomicroscope for qualitative evaluation of microleakage. The data were statistically analyzed by Mann-Whitney U and Wilcoxon matched pairs signed ranked tests. Extra specimens were analyzed with the scanning electron microscope (SEM). Occlusal margins (enamel margins) resulted in statistical lower degree of leakage than gingival margins (dentin/cementum margins) in both treatment groups. For each type of margin, there were no statistically significant differences between the etched and the etched and deproteinized groups. Under the SEM, occlusal surfaces showed no detachment between enamel and dentin, while dentin/cementum resulted in gap formation. PMID- 11203863 TI - Retentive strength of an amalgam bonding agent: chemical vs light vs dual curing. AB - Dentin bonding agents have been shown to enhance retention of amalgam restorations by mechanical means. Little research is available on which mode of curing may optimize amalgam bonding. This in vitro study compared the bond strengths exhibited by three variations of a bonding agent, each using a different curing mode, with two earlier versions of amalgam resin liners and cavity varnish. The six test groups of lining agents for amalgam restorations included [C] chemical-cured, [L] light-cured and [D] dual-cured versions of one filled adhesive resin (Clearfil Liner Bond 2V), [LF] Light-cured, Filled resin (Clearfil Liner Bond 2, Kuraray Co.); [LCF] Light- and Chemical-cured, Filled resin Clearfil Liner Bond + Protect Liner, Kuraray Co) and [V] Varnish (Copalite, Cooley & Cooley, Ltd). For each group, 20 Class V cavity preparations were cut in human molars. The preparations were 2.5 mm deep and 3 mm wide at the pulpal floor, with a slightly divergent taper. After treating the preparation with the bonding agent, a 3/4 inch, 18 gauge flat-headed wire nail was seated in the cavity with its head at the pulpal floor of the preparation, and Tytin amalgam (Kerr Corp, Romulus, MI) was condensed into the preparation around the nail. All restorations were stored for 24 hours in distilled water at 37 degrees C, then subjected to 2500 thermal cycles (8 degrees C to 58 degrees C). After one week the samples were tested to failure in tension using an Instron Universal Testing Machine (crosshead speed = 2 mm/min) and peak load (kg) was recorded. Significant differences in retention were found using ANOVA and the Games & Howell post hoc test (p = 0.05). The mean loads at failure (+/- SD) were C 13.1 (+/- 2.4), L 21.8 (+/- 6.1), D 26.8 (+/- 7.4), LCF 23.8 (+/- 7.4), LF 21.4 (+/- 3.3) and V 2.0 (+/- 1.8). All dentin-bonding agents exhibited significantly greater retention than the varnish. While the bond strengths of the dual cured (D) and the light-cured (L) liners were not significantly different from one another, both were significantly higher than the chemically-cured (C) resin liner in terms of retention. PMID- 11203864 TI - Evaluation of dental adhesive systems with amalgam and resin composite restorations: comparison of microleakage and bond strength results. AB - A variety of laboratory tests have been developed to assist in predicting the clinical performance of dental restorative materials. Additionally, more than one methodology is in use for many types of tests performed in vitro. This project assessed and compared results derived from two specific laboratory testing methods, one for bond strength and one for microleakage. Seven multi-purpose dental adhesives were tested with the two methodologies in both amalgam and resin composite restorations. Bond strength was determined with a punch-out method in sections of human molar dentin. Microleakage was analyzed with a digital imaging system (Image-Pro Plus, Version 1.3) to determine the extent of dye penetration in Class V preparations centered at the CEJ on both the buccal and lingual surfaces of human molar teeth. There were 32 treatment groups (n = 10); seven experimental (dental adhesives) and one control (copal varnish, 37% phosphoric acid) followed by restoration with either amalgam or resin composite. Specimens were thermocycled 500 times in 5 degrees and 55 degrees C water with a one-minute dwell time. Bond strength and microleakage values were determined for each group. ANOVA and Student-Newman-Keuls tests demonstrated an interaction between restorative material and adhesive system with a significant difference among adhesives (p < 0.05). Using a multi-purpose adhesive system resulted in both a statistically significant increase in bond strength and a statistically significant decrease in extent of microleakage (p < 0.05). The effect of the adhesive upon both microleakage and bond strength was greater in the resin composite restorations than in the amalgam restorations. Bond strength testing was more discriminating than microleakage evaluation in identifying differences among materials. PMID- 11203865 TI - Color stability of fluoride-containing restorative materials. AB - Six fluoride-releasing materials of shade A3 were tested: one glass ionomer (Fuji IX), one resin-modified glass ionomer (Photac-Fil), two compomers (F 2000 and Dyract AP) and two composites (Tetric Ceram and Solitaire). Disk-shaped specimens of each material were prepared according to manufacturer's instructions, polished and L*a*b* baseline measurements taken. Specimens were randomly divided into two groups and given four different treatments of UV light exposure and immersion in a staining solution. Chromo Meter color measurements were taken following each treatment. Two-way ANOVA and Duncan Multiple Range post-hoc tests were used to compare color changes as a function of the four treatment conditions and one-way ANOVA was used to compare materials for each treatment separately. The results showed significant difference in shade A3 between products. In general, the hydrophobic materials showed greater color stability and stain resistance than the hydrophilic materials. Tetric ceram had the best color stability and stain resistance, while Fuji IX had the least. PMID- 11203866 TI - The effect of tooth preparation on microleakage behavior. AB - Many factors contribute to the microleakage of a restoration. One of the more important is the method of cavity preparation. This study compared the microleakage behavior of composite restorations placed in cavities prepared by different techniques. It also compared and correlated the microleakage data produced by an electrochemical vs a staining technique. Class V cavities were prepared in 48 premolars by four techniques: (1) tungsten carbide bur in a high speed handpiece followed by acid etching; (2) air abrasion (27 microns Al2O3) followed by acid etching; (3) air abrasion (50 microns Al2O3) and (4) air abrasion (27 microns Al2O3), with n = 12 in each group. All teeth were restored with Prime and Bond 2.1 and Tetric Flow, then thermocycled between 5 degrees and 55 degrees C for 5000 cycles with a one minute dwell at each temperature. After thermocycling, a PVC-covered Cu wire was inserted apically into the pulp chamber of each tooth and sealed into position. Leakage was continuously followed by a conductimetric method for 75 days. The teeth then were immersed in 50% AgNO3 for two hours, rinsed in distilled water for 60 seconds, then placed in a rapid photographic developer solution for two hours, followed by rinsing and sectioning for microscopic examination. Electrochemical data were examined by ANOVA and Newman-Keuls multiple comparison tests, while Kruskal-Wallis and Rank Sum Difference tests were used on the staining evaluations. Spearman's rho test was used to correlate the two test techniques. Electrochemical data for cavities prepared with a bur or air abrasion followed by acid etching prior to restoration showed significantly less (p < or = 0.05) microleakage (mean leakage currents of 1.89 & 1.57 microA, respectively) than teeth prepared with air abrasion alone (mean leakage currents of 3.60 & 3.40 microA, respectively). Rank sum AgNO3 staining data (196 & 242 vs 371 & 368) supported these findings. The correlation between the electrochemical and staining data was significant (p < or = 0.05) for all four groups of test specimens. PMID- 11203867 TI - Effect of finishing and polishing procedures on the surface roughness of packable composites. AB - This study examined the average surface roughness (Ra, micron) of three packable composites and one hybrid composite cured against mylar, before and after treatment with a fine finishing diamond bur, a resin finisher followed by fine and extrafine polishing paste, two silicone-based finishing and polishing systems, fine and super-fine aluminum-oxide polishing disks, a silicon carbide impregnated polishing brush and a surface-penetrating composite sealant. Additionally, the Ra was examined for one of the packable composites before and after treatment with a finishing carbide, prior to the finishing and polishing procedures detailed above. The finishing diamond significantly increased the Ra for all composites (ALERT, SureFil, Solitaire and Z-100). The finishing carbide used with SureFil (SureFil + C) also increased the Ra; however, it also produced surfaces up to 3.5x smoother when compared to SureFil surfaces finished with the diamond. Overall, Sof-Lex Contouring and Polishing Discs were able to produce the smoothest surfaces, followed by the Jiffy Composite Polishing Cups, the Enhance Composite Finishing & Polishing System/Prisma-Gloss Composite Polishing Paste, the Diacomp Intra-Oral Composite Polishers and the Jiffy Composite Polishing Brushes, respectively. The smoothest surfaces were produced using Z-100, followed by SureFil + C (carbide finishing bur), Solitaire, SureFil and ALERT, respectively. In general, Protect-It Composite Surface Sealant had little effect on the Ra, except with ALERT, where a slight increase in Ra was observed. PMID- 11203868 TI - Handpiece coolant flow rates and dental cutting. AB - High-speed handpieces incorporate water coolant sprays to remove cutting debris and minimize thermal insult to the pulp. Little data exists on optimal coolant flow rates during clinical procedures. This study compared the effect of different coolant flow rates on diamond stone cutting efficiency. Cutting studies were performed on Macor machinable ceramic using a previously developed test regimen--a KaVo high-speed handpiece at a cutting force of 91.5 g (0.9 N). Cutting was performed with round end tapered medium grit diamond stones under cooling water flow rates of 15, 20, 25, 30 and 44 ml/min, with cutting rates determined as the time to transect the 13 mm square cross-section of the Macor bar. Each bur was used for five cuts, with six burs used for each flow rate, for a total of 150 measurements. The data were analyzed by one-way ANOVA with a post hoc Scheffe test. The cutting studies indicated that diamond stone cutting rates increased with higher coolant flow rates over the range of 15-44 ml/min. The data suggest that higher coolant flow rates promote cutting efficiency. PMID- 11203869 TI - Effects of cavity form and setting expansion of refractory dies on adaptability of Class II (MO and MOD) fired ceramic inlays. AB - This study investigated the effects of cavity divergence and setting expansion of refractory die material on the adaptability of Class II (MO and MOD) fired ceramic inlays. Standardized Class II (MO and MOD) cavities with two kinds of lateral wall divergence (10 and 20 degrees) were prepared in epoxy resin blocks. A refractory die was prepared from an impression of the epoxy resin cavity in which the setting expansion ranged from 0.04 to 1.14%. A ceramic inlay was fired on each die. The fabricated inlay was inserted into the epoxy resin cavity, and the interfacial distance between the ceramic inlay and the cavity wall at the margin was measured using a reflecting microscope at x100 magnification. The internal fit was measured after sectioning the specimen longitudinally. The results indicate that the setting expansion of the refractory die materials and the divergence of the lateral walls had significant effects on the adaptability of Class II (MO and MOD) fired ceramic inlays. The inlays fabricated on the refractory dies with small setting expansion showed small internal gaps in Class II (MO) cavities. Significantly good adaptation was achieved when the setting expansion was 0.32% or less (p < 0.05). The inlays fabricated on the refractory dies with large setting expansion showed small internal gaps in Class II (MOD) cavities. Significantly good adaptation was achieved when the setting expansion was 0.87% and greater (p < 0.05). PMID- 11203870 TI - Dental care of elderly in nursing homes: perceptions of managers, nurses, and physicians. AB - Epidemiologic studies have shown that the oral health of residents in nursing homes is poor. This can be due to their impaired ability to maintain appropriate oral hygiene or to a lack of interest in oral care among those responsible for the care. The purpose of this study was to assess the attitudes of managers, caregivers, and physicians with regard to oral health care issues of their residents. A questionnaire sent to the managers of the 65 nursing homes in Geneva was returned by 47 (69%). According to the managers, 85% of the nursing homes organized transportation for the residents to a dental office; dental care with follow-up treatment was organized in 79% of the facilities; 68% of the facilities organized treatment for dental emergencies. Another questionnaire was distributed to 169 caregivers in 13 nursing homes. A majority had received no education in oral hygiene care of the residents. The caregivers did accept responsibility for oral hygiene care, but preferred to share it with a dentist responsible for the oral health care of the residents. Only 33% of the physicians indicated that they carried out a systematic examination of the oral cavity, and 20% agreed that the oral cavity might be an integrated part of the body. The majority of the physicians were in favor of more information on oral diseases and regular visits by a dentist; however, close collaboration with a dentist on oral health issues had a low priority. PMID- 11203871 TI - Effects of short professional mechanical tooth-cleaning (PMTC) program in young adults with mental disabilities. AB - We evaluated the usefulness of a short professional mechanical tooth-cleaning (PMTC) program to improve periodontal conditions and caries susceptibility in 10 young adult patients with mental and/or physical disabilities. The PMTC program was carried out once on each of 6 sextants of the full mouth during 6 visits at two-week intervals. Even one treatment with PMTC was found to be significantly effective in reducing the probing depth in eight of the 10 subjects. A reduction in the total number of bleeding sites on probing was also clearly observed in all subjects. Moreover, the debris index was reduced in nine subjects by the PMTC program. Although caries susceptibility was improved, albeit very slowly, by PMTC, the Cariostat pH values showed no consistent tendency. The effects lasted for more than 6 weeks. Analysis of these results suggests that the PMTC program can be effective in adults with mental disabilities, especially in reducing gingival inflammation. PMID- 11203872 TI - Nursing directors' perceptions of the dental components of the Minimum Data Set (MDS) in nursing homes. AB - The Directors of Nursing (DON's) of all 428 nursing homes in the state of Iowa were sent a pre-tested questionnaire. The aim of the study was to examine the perceptions by nursing directors on the utility of a dental component of the Minimum Data Set (MDS) in identifying residents with dental problems in their facility. The return rate was 55.1% from the DON's. It was reported that 66.4% of the homes had a training program for the MDS and that in 38.0% of the homes there was only one person doing the assessments. The majority (76.0%) of the DON's stated that the MDS was useful in tracking residents and that it did help them to identify dental problems. When asked how often it was useful in the identification of dental needs, only 9% stated that it was often useful. Also, regarding frequency of dental appointments for the residents, a mean of 51.0% of residents were estimated to have received some dental care during the previous year (means of 33.2% at the facility, 22.4% at a dental office, and 0.4% in a hospital). If change is to occur, the dental profession must try to get the nursing home assessors to convince the nursing homes to use the oral/nutritional/dental sections of the MDS as they were intended under the OBRA regulations. PMID- 11203873 TI - Dental care access among individuals with Down syndrome in France. AB - The aim of this study was to compare levels of dental care utilization, receipt of dental services, and oral hygiene habits between a sample of individuals with Down syndrome (DS) and their siblings. Data were collected by means of a recently validated, French-language, questionnaire measured of oral health and its related problems for individuals with DS. A cross-sectional survey was undertaken of parents of children with DS attending a national meeting for families and carers of individuals with DS in France. Older individuals with DS were significantly more likely to visit a dentist regularly than their older non-DS siblings, but the group with DS was significantly less likely to have received any dental treatment. The group with DS was significantly more likely to have difficulty finding both medical and dental services. Parents were nearly twice as likely to report problems finding dental services for their child with DS as they were medical services. In a multiple logistic regression analysis within the DS group, it was found that older age, regular speech therapy and ophthalmology consultations, and reports of no difficulty finding a dentist were independently associated with increased odds for regular dental consultations. Analysis of the findings suggests that the parents of children with DS in France frequently encounter problems of access to oral health care and that individuals with DS are less likely to receive dental services than are their non-DS siblings. PMID- 11203874 TI - Walk-in emergency patients have always been a mixed blessing for most dental departments in hospitals. PMID- 11203875 TI - "It's not easy being green...". PMID- 11203876 TI - EMTALA: impact on hospital dentistry emergency services. AB - The Emergency Medical Treatment and Active Labor Act (EMTALA) requires hospital based dental residency programs and hospital dentists to meet Federal standards when patients come to a hospital emergency department and need emergency dental services. EMTALA (42 U.S.C. 1395dd) has three key provisions which must be understood because of its impact on hospital emergency dental services: Medical Screening Requirements, Necessary Stabilizing Treatment for Emergency Medical Conditions, and Restricting Transfers Until the Individual is Stabilized. This article reviews the relevant Federal statutes, codes of Federal regulation, and published court cases to help practitioners understand the issues. An understanding of the informed consent process, including the "informed refusal" doctrine, as well as the dentist's obligation when patients refuse recommended diagnostic tests, treatment, or transfer, is important. Immunity for failure to obtain informed consent is sometimes appropriate under state law. Under EMTALA, the term "physician" applies to dentists. Recent changes clarify distinctions between the terms "on campus" and "off campus" related to hospital property emanating from the "Ravenswood" tragedy. Hospital dentists must be familiar with these requirements when caring for patients seeking emergency services. PMID- 11203877 TI - Recent advances in diabetes mellitus of interest to dentistry. AB - Significant changes were made in 1997 by The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus of the American Association of Diabetes regarding the diagnosis and classification of diabetes mellitus. The terms "insulin-dependent diabetes mellitus" (IDDM) and "non-insulin-dependent diabetes mellitus" (NIDDM) were dropped. The new classification is, in general, based on etiology rather than on treatment and includes four groups: Type I (autoimmune), Type 2 (non-autoimmune), Other specific types, and Gestational diabetes. The fasting blood glucose level for diagnosis was lowered from 140 mg/dL to 126 mg/dL. A random blood glucose of 200 mg/dL or greater in a patient with symptoms of diabetes is diagnostic. Each of these diagnostic tests needs to be repeated on a separate day. The glucose tolerance test is no longer recommended for routine diagnostic use. Recommendations for the screening of diabetes mellitus in presumably healthy individuals are presented. New advances in insulin and its delivery to the diabetic patient are discussed. The impact of diabetes mellitus on the oral cavity is updated. PMID- 11203878 TI - Dental caries history in nine children with chromosome 18p deletion syndrome. AB - Chromosome 18p deletion syndrome is caused by the deletion of a portion of genetic material on the short (p) arm of chromosome 18. Many of 100 prior case reports in the medical literature describing the dental health of subjects with this syndrome reported multiple caries associated with the syndrome. At the third annual international conference of The Chromosome 18 Registry & Research Society, dental examinations were carried out on nine children with chromosome 18p deletion syndrome and five of their unaffected siblings. The dental examination included an intra-oral evaluation of coronal decay and filled permanent teeth surfaces (DFS) and decayed and filled primary tooth surfaces (dfs) using a mouth mirror, explorer, and a high-intensity fiber optic light. An evaluation of the data revealed that five of nine children with 18p deletion syndrome (56%) were free of tooth decay or a history of tooth decay. Four of the nine (44%) had tooth decay or a history of tooth decay. The prevalence of decay was quite similar in the genetically unaffected siblings. Three of the five (60%) unaffected siblings of the children with 18p were free of tooth decay, whereas two of the five (40%) had tooth decay. One of the affected children had a missing mandibular left central incisor. None of the children had abnormally shaped teeth. The caries pattern seems to be similar to that reported in the NHANES III data collected in the United States from 1988-1991. Analysis of these preliminary data suggests that the risk for caries in chromosome 18p deletion syndrome may be lower than previously reported. PMID- 11203879 TI - Desensitization of the gag reflex in an adult with cerebral palsy: a case report. AB - Severe oral hypersensitivity and aversive oral behaviors present a significant barrier to dental treatment and compromise oral health status. Although several authors have addressed the reduction of oral hypersensitivity and aversive behaviors (such as gagging, retching, and vomiting) in the otherwise well dental patient, treatment for patients with severe disability has not been explored. The successful management of oral hypersensitivity and aversive behavior can have significant health benefits. These can be described via an outcomes paradigm as physical and social benefits for the patient, psychological benefits for the patient, carer, and practitioner, and organizational benefits for the institutions providing dental care and medical management. This paper summarizes the management of a severely disabled patient whose aversive behaviors were eliminated with non-invasive therapy techniques. Oral hygiene was facilitated and health benefits were identified across a number of domains following successful multi-disciplinary management. PMID- 11203880 TI - Non-institutionalized elderly dental patients in Israel: socio-demographics, health concerns, and dental anxiety. AB - The purpose of this study was to evaluate which factors might influence health care attitudes such as anxiety about dental care by older adults in Israel. The study population consisted of 103 non-institutionalized patients (46 men and 57 women) over the age of 65 who attended a dental clinic that provided services for older adults during a one-year period. Socio-demographic information and information about the subjects' general health and their level of concern about health problems were obtained from self-reported questionnaires, while the dental anxiety level was found by means of a dental anxiety scale (DAS). Ninety-nine percent of the patients suffered from a major systemic disease such as diabetes, hypertension, atherosclerosis, respiratory disease, and rheumatic disease. Both unmarried and first-time patients expressed high anxiety scores. Patients with 12 or fewer years of formal schooling demonstrated significantly higher dental anxiety. Among patients who regularly attended a synagogue or a social club, concern about oral health was significantly higher than for the rest (p < 0.02). No association was found between having dentures and gender, or between having dentures and level of education. The reason for visiting the clinic (inability to eat, pain, or esthetics) was not associated with any other health concern or with dental anxiety levels. This study determined that patients who were unmarried, less educated, or attending the facility for the first time were more likely to experience dental anxiety. These patients merit special consideration. PMID- 11203881 TI - Effect of an oral health training program on knowledge and behavior of state agency long-term-care surveyors. AB - This study examines the effect of a training program on long-term-care (LTC) surveyors' knowledge of factors affecting oral health and their behavior in citing oral health deficiencies of LTC residents. Twenty surveyors were recruited for the experimental group, along with a non-equivalent comparison group of 31 surveyors. The experimental group participated in a three-hour interactive, case based training program. The experimental group had a significant increase in total knowledge (p < 0.002) post-test scores with a moderate effect size, eta 2 = 0.115. The training program resulted in a statistically significant increase (p < 0.0001) in oral health citation behavior for the experimental group for six months following training. This study provides evidence that an interactive case based training program can affect participants' knowledge regarding oral health of LTC residents and participants' oral health citation behavior. As the elderly population experiences an increased life expectancy with increased need for assistance with Activities of Daily Living (ADL), similar training programs will become an important factor in assessing the quality of care provided to LTC residents. PMID- 11203882 TI - Oral health needs of elderly short-term patients in a geriatric department of a general hospital. AB - The purpose of this study was to estimate the realistic dental needs of an elderly short-stay patient in a geriatric department. One segment of the elderly population at risk for whom surveillance would appear extremely important are those admitted temporarily to the hospital for acute or acute-on-chronic care. Little has been written about the oral needs of such patients. The study population was comprised of 468 patients of a geriatric department in a medical center examined by a dentist trained in gerodontics. An evaluation of the results showed that 65.3% needed direct oral hygiene assistance. Only 16.4% are able to participate in oral hygiene instruction; a few of them--6.6%--had a need of prosthodontic treatment. A once-weekly screening program was required to handle the oral problems, mainly Candida infections. Close cooperation with the ward staff is essential in order to develop and promote good oral hygiene for this very frail elderly population. PMID- 11203883 TI - Evaluation of an oral health education program for nursing personnel in special housing facilities for the elderly. Part II: Clinical aspects. AB - In Sweden, efforts are being made to create strategies for evaluating realistic dental treatment needs among the elderly, who are retaining more natural teeth. These strategies focus on the importance of maintaining adequate oral hygiene. Elderly in long-term-care facilities often depend on nursing personnel for carrying out daily oral hygiene procedures. Therefore, the nursing personnel's knowledge about and attitudes toward oral health make oral health education for health care professionals an important concern. The purpose of this study was to evaluate the clinical oral health outcome in residents after their caregivers had undergone a one-session, four-hour oral health education program. The study consisted of an intervention with a pre- and a post-test and was carried out in three municipalities in the southwestern part of Sweden. A newly developed oral health screening protocol was carried out for 170 subjects living in long-term care facilities both before and 3-4 months after nursing personnel had attended an oral health education program. Following the intervention, a statistically significant improvement was recorded for changes in oral mucosal color, a modified plaque index which measured oral hygiene status, and a mucosal index which recorded mucosal inflammation. This study indicated that a limited, one session, four-hour oral health education, offered to caregivers within long-term care facilities, had a positive impact on the oral health status of residents. PMID- 11203884 TI - Characteristics of dental emergency clinic patients with and without disabilities. AB - This study compared oral health and demographic characteristics of patients with and without disabilities at a dental school emergency clinic. Of 407 consecutive patients surveyed, 20.4% reported disabilities. Two groups matched by age and gender, those with disabilities (DIS, n = 79) and those without disabilities (ND, n = 177), were compared on questionnaire responses; two subgroups, DIS (n = 38) and ND (n = 44), were assessed clinically. The mean ages of the DIS and ND groups were 44.0 years (SD +/- 11.6) and 43.0 years (SD +/- 12.3), respectively. By chi squared analysis, DIS vs. ND subjects had significantly lower levels of education, employment, income, and dental insurance, and greater dependence on Government funding. In the DIS group, 79.5% were not working, while 6.4% did work regularly. In the ND group, the corresponding values were 30.9% and 46.9%, respectively. In the DIS group, 51.9% identified Medicaid acceptance as the reason they sought care at the clinic, while 62.7% of the subjects in the ND group identified the lower fee structure as the reason for clinic selection. More DIS than ND subjects reported dentists' unavailability and inability to manage the disability, lack of transportation, effect of dental problems on health, and referral by a health professional. DIS vs. ND subjects had significantly fewer sound teeth and more missing teeth. The results suggest that one in five dental school emergency clinic patients has disabilities. PMID- 11203885 TI - New information for our special care of patients with dementia. PMID- 11203886 TI - General anesthesia protocol for the dental patient: emphasis for older adults. AB - As the population ages, with increased retention of the natural dentition, there will be a greater responsibility for dental professionals to maintain the oral health of medically, behaviorally, cognitively, and physically impaired adults. Oral sedatives and nitrous oxide analgesia are frequently and successfully used for dental treatments in these patients. However, many compromised older adults cannot safely tolerate dental treatment with these sedative techniques in an outpatient setting. This paper describes the use of general anesthesia in a hospital environment, coordinated with medical and anesthesia specialists, that is a viable, safe, and effective treatment tool for providing comprehensive dental and oral surgical treatment for the older patient. PMID- 11203887 TI - Medicare, prevention, and dentistry: implications of the Institute of Medicine report, extending Medicare coverage for preventive and other services. PMID- 11203888 TI - Hospital-based dental care for persons with disabilities: a study of patient selection criteria. AB - The objective of this investigation was to generate a medical and dental profile of patients attending the Mount Sinai Hospital Dental Program for Persons with Disabilities, to determine if certain selected criteria could identify patients likely to require dental care in that setting. The need for dental care under general anesthesia was used as the prime indicator that care should be provided in a hospital setting. A retrospective review of all the charts of the patients enrolled in this hospital program was undertaken. Results indicated that patients who were treated in this hospital-based dental program had the following characteristics: moderate to profound mental retardation (39.5%), moderate to severe behavioral problems (31.1%), and/or a history of seizure activity (29.1%). Behavioral criteria appear to be the predominant reason for the provision of hospital-based dental care for persons with disabilities. PMID- 11203889 TI - The dental management of a patient with a cocaine-induced maxillofacial defect: a case report. AB - There are several dental complications associated with cocaine abuse, including adverse reactions to dental anesthetics, post-operative bleeding, and cellulitis, which can lead to necrosis of orbital, nasal, and palatal bones. Following is a report of the initial treatment rendered to a patient who had destroyed most of her hard palate over a ten-year period of cocaine abuse. There are no classic socio-economic or educational profiles for abusers of cocaine. Drug abuse victims may present as patients in any dental office. Though there are certain classic physiological and psychological symptoms of their condition, they may not display symptoms at all. PMID- 11203890 TI - Cleft lip and/or palate in the west of Ireland, 1980-1996. AB - The aim of this study was to identify and investigate care for children born, over a 17-year period (1980-1996), with cleft lip and/or palate (CL/P) in the Western Health Board region of Ireland. One hundred and six cleft-affected children were identified. The incidence was 1.14 per thousand (1:871) live births. Epidemiological findings in relation to cleft type, gender, family history, and location followed international trends. The establishment of a national Register with mandatory reporting of children with CL/P in Ireland would ensure greater consistency in data collection and may help improve co-ordination of care. PMID- 11203891 TI - Behavior management and communication strategies for dental professionals when caring for patients with dementia. AB - The impact of dementia and associated behavioral problems on the oral health of long-term-care-facility residents is increasing. The provision of oral hygiene care for these cognitively impaired residents is difficult and complex. Dental professionals and carers need good communication skills with cognitively impaired residents, and specific strategies for the management and prevention of their behavioral problems. Newer philosophies of dementia care enable dental professionals and carers to use more individualized and non-pharmacological approaches for dental treatment and preventive oral care provision. This paper reviews behavior management and communication strategies from the dental literature, and newer techniques and interventions from dementia research and literature. PMID- 11203892 TI - Dental self-care among dentate adults: contrasting problem-oriented dental attenders and regular dental attenders. AB - Self-care behaviors are common and can act as substitutes for or supplements to formal health care services. We tested the hypothesis that problem-oriented dental attenders (POAs) report more dental self-care behaviors than do regular dental attenders (RAs), presumably as a substitute for professional care. The Florida Dental Care Study is a longitudinal cohort study of changes in oral health, in which we measured dental self-care behaviors related to three common dental problems: toothache pain, bleeding gums, and tooth loss. Despite using less dental care, POAs were less likely to report "conventional" methods as means to prevent the three dental problems; however, they were more likely to report that homemade remedies, topical medications, or mouthwashes were ways to prevent or treat these problems. POAs were also more likely to believe that "nothing can be done" to prevent these problems. Additionally, POAs had more negative dental attitudes, used less dental care during follow-up, had more dental disease, were the only persons who extracted at least one of their own teeth, and were more likely to use tobacco. With the exception of dental self-extractions, no single self-care belief or behavior distinguished POAs from RAs, nor were POAs likely to have different explanations for dental problems. Instead, the pattern was one of modest differences on a number of items. Although POAs use less dental care, they do not compensate by employing more "conventional" dental self-care behaviors, but report being more likely to employ "unconventional" behaviors. They also are more likely to believe that nothing can be done to prevent dental problems. PMID- 11203893 TI - Oral health is not an isolated dental problem. PMID- 11203895 TI - Development and evaluation of a multimedia resource pack for oral health training of medical and nursing staff. AB - A resource pack has been devised for training medical and nursing staff and other carers in order that they may recognize oral disease and carry out routine oral care and treat common oral disorders. The custom-designed folding pack contains a videotape, a CD-ROM disc, and an A5-sized spiral-bound booklet, together with wall posters and a list of useful addresses. One hundred of the packs were distributed across Scotland to medical, nursing, and dental staff involved in postgraduate medical and nursing education. The packs were independently evaluated by an external organization through a questionnaire and also by telephone interviews. The pack received very positive responses, and 35% of the respondents reported making changes to their current practice. A long-term measure of success, beyond the scope of this paper, will depend on the measurement of improved quality of oral health care of the patients in those institutions where the pack has been used in training. PMID- 11203894 TI - The epidemiology of non-albicans Candida in oropharyngeal candidiasis in HIV patients. AB - Oropharyngeal candidiasis (OPC) is the most common fungal infection in patients with HIV infection. Fluconazole has been proven to be very effective in treating this infection, but decreased susceptibility of Candida to this drug has emerged. Certain non-albicans species such as C. glabrata and C. krusei are commonly less susceptible to fluconazole than C. albicans and are being isolated with increased frequency in HIV patients. The purpose of this study was to determine if the presence of non-albicans Candida with OPC in HIV patients had an impact on clinical presentation. This study shows that late-stage HIV patients have a high prevalence of Candida with decreased susceptibility to fluconazole, especially non-albicans species. OPC episodes with non-albicans isolates were more likely to require higher doses of fluconazole to achieve clinical cure. Also, the presence of non-albicans Candida was more frequently associated with severe symptoms. PMID- 11203896 TI - Early tooth loss due to cyclic neutropenia: long-term follow-up of one patient. AB - In young patients with abnormal loosening of teeth and periodontal breakdown, dental professionals should consider a wide range of etiological factors/diseases, analyze differential diagnoses, and make appropriate referrals. The long-term oral and dental follow-up of a female patient diagnosed in early infancy with cyclic neutropenia is reviewed, and recommendations for care are discussed. PMID- 11203897 TI - Assessment of objectives of post-doctoral general dentistry programs in Canada. AB - Objectives of hospital-based post-doctoral general dentistry programs in Canada were assessed by questionnaire. Seventy percent (14 of 20) of the program directors responded. Educational goals and objectives were assessed in professional skills and practice management, public health and preventive dentistry, oral medicine and pathology, special needs patient care, trauma and emergency care, restorative/prosthodontic care, endodontics, orthodontics/pediatric dentistry, oral surgery, periodontics, pharmacology, and functioning in a hospital. High rankings of proficiency were related to primary care, restorative/prosthodontic, endodontic, and surgical care. Emergency care, sedation, and pharmacology were also ranked highly. Lower rankings of proficiency were reported in orthodontics, aspects of public health dentistry, practice management, and advanced oral and maxiliofacial surgery. When the results of the Canadian survey were compared with those of a survey of US post-doctoral general dentistry programs, substantial similarity was seen. The findings support continuing reciprocity in accreditation standards between the Canadian and American Commissions on Dental Education and Dental Accreditation. PMID- 11203898 TI - The relationship between place BANA reactivity and clinical parameters in subjects with mental disabilities. AB - The purpose of the present investigation was to determine whether subjects institutionalized with mental retardation have a relationship between periodontal clinical parameters and the presence of the BANA-positive periodontal pathogens Porphyromonas gingivalls, Treponema denticola, and Bacteroides forsythus in their subgingival plaques. Fifty institutionalized subjects (25 patients with Down syndrome and 25 subjects with mental retardation) were matched with respect to age and sex. Periodontal clinical parameters (Bleeding on Probing, BOP; Papillary Bleeding Score, PBS; and Probing Depth, PD) were obtained from 6 reference teeth (3, 8, 14, 19, 24, 30). In addition, subgingival plaque samples taken from the same 6 teeth were analyzed for the presence of the BANA-positive species, by means of the chairside BANA test. In both the patients with Down syndrome and the group with mental retardation, the presence of BANA-positive plaques was significantly associated with bleeding on probing (p < 0.05) and increased probing depth (p < 0.01, Chi-square). Analysis of these data indicated that the BANA test could be used in combination with clinical criteria to diagnose a periodontopathy anaerobic infection in institutionalized subjects. PMID- 11203899 TI - Evaluation of a long-term oral health program by carers of children and adults with intellectual disabilities. AB - The oral health program presented here was undertaken in three French centers for persons with special needs. The program aimed to educate the carers about dental disease, to motivate them with regard to prevention, and to improve the oral hygiene and oral health of the residents. This study evaluated the impact of the program in terms of change in attitudes and behavior expressed by the carers by means of a questionnaire. Following demonstration of oral hygiene techniques on an individual basis, the number of residents who had their teeth cleaned more than once a day rose from 24% to 52% (p < 0.05). The percentage of carers able to clean both posterior and anterior teeth of their key residents increased from 24% to 60% (p < 0.05), and the percentage finding tooth cleaning easy increased from 36% to 60% (non-significant). The intervention was thus deemed moderately successful, although the carers continued to take better care of their own oral health than that of the residents. The need for ongoing training is emphasized, both for the carers of those with special needs and for the dental profession. The lack of a validated means of measuring the impact of such interventions on care providers for this population is discussed. PMID- 11203900 TI - Hepatitis: still a concern? AB - Although some forms of viral hepatitis were identified more than 50 years ago, hepatitis continues to have an impact on the practice of dentistry. Possible transmission in the dental setting, management of the chronically ill, and legal issues related to treatment of infectious patients combine to emphasize that hepatitis is still an important issue for dental health care workers. Currently, 7 viral forms are recognized. Those with predominantly enteral modes of transmission--including HAV, HEV, and HFV--are of minor concern in the dental environment. HBV, the most infectious blood-borne pathogen, has been largely controlled in this country by vaccination and the use of universal precautions. HDV is an incomplete virus that has HBV infection as a prerequisite. HCV is of great concern today for several reasons. A high percentage of HCV infections results in chronic disease. Most cases remain asymptomatic for an extended period of time, and many have no identifiable risk factors. Currently, no vaccination is available for HCV. Patients infected with HCV present a management challenge, because they may ultimately develop serious liver dysfunction. In fact, HCV infection is presently the most common reason for liver transplantation. By understanding the various forms of viral hepatitis and following recommended infection control and vaccination protocols, the dental healthcare worker can treat infected patients in a manner that is safe for both patients and dental health care workers. PMID- 11203901 TI - A combined direct dowel and indirect core technique. AB - The dowel-and-core restoration is indicated when inadequate tooth structure remains to retain an extracoronal restoration. A modified technique for fabricating the dowel and core combines the direct technique of forming the dowel in the actual channel with the indirect technique of creating an ideal core contour in the laboratory. This technique allows the operator to create an accurate and passive fit of the dowel pattern in the canal preparation. The technique also introduces the option of retrieving the dowel portion by utilizing a polyvinyl siloxane cast or liner. Further advantages of the technique are reduced chairside time and the ability to capitalize on the preparation of multiple teeth. The technique focuses efforts on achieving an accurate and passive fit of the dowel clinically while delegating the formation of the core to the laboratory. PMID- 11203903 TI - The laws of physics have not changed. PMID- 11203902 TI - A 3-year follow-up study of preformed beta-quartz glass-ceramic insert restorations. AB - OBJECTIVE: The purpose of this study was to evaluate the clinical performance of preformed beta-quartz glass-ceramic insert restorations. METHODS AND MATERIALS: Nine Class I and 30 Class II beta-quartz glass-ceramic insert restorations were placed in 16 patients who were seen regularly by personnel at Umea University Dental School. The California Dental Association criteria were used to evaluate the restorations at baseline, 6 months, and 1, 2, and 3 years after luting. The occurrence of postoperative sensitivity, the time taken to manufacture each restoration, and certain periodontal conditions were also evaluated. RESULTS: Sixty-nine percent of the restorations were rated satisfactory at the 3-year examination. During the follow-up period, 4 became loose and 7 were fractured or had flaking surfaces. Caries was registered in connection with 1 restoration. Excellent ratings were obtained for marginal integrity, anatomic form, surface, and color in 62%, 84%, 32%, and 44% of the restorations, respectively. There was no statistically significant difference in the occurrence of plaque and bleeding on probing in comparison with the controls. The mean overall time for placement was 38 minutes. The estimated survival rate (Kaplan-Meier) was 59% after 3.5 years. CONCLUSION: The quality of the beta-quartz glass-ceramic restorations in the present study was inferior to that presented in most earlier studies of ceramic or resin composite posterior restorations placed in patients treated at university clinics. Both the technique and the beta-quartz glass-ceramic inserts have to be evaluated in more long-term studies to assess the possibility of their serving as an alternative restorative technique. PMID- 11203904 TI - In vitro study of needle deflection: a linear insertion technique versus a bidirectional rotation insertion technique. AB - OBJECTIVE: Deflection of dental needles during tissue penetration has been associated with a failure to achieve successful anesthesia. The purpose of this study was to determine whether needle deflection in a tissuelike substance could be minimized through the use of a bidirectional rotation insertion technique. METHOD AND MATERIALS: Three in vitro deflection test models were constructed, each incorporating a different tissuelike substance of a different density. Each substance was tested with 3 different needle sizes (30-guage, 27-gauge, and 25 gauge). A customized dental surveyor allowed for standardized needle insertions to a standardized depth of 20 mm. Two different insertion techniques, a linear insertion technique and a newly described bidirectional rotation insertion technique, were tested. Radiographic analysis was performed after each insertion. RESULTS: The bidirectional rotation insertion technique described was consistently more effective in minimizing needle shaft deflection for 30-, 27-, and 25-gauge needles. The differences were statistically significant. Each of the different tissuelike substances consistently demonstrated this reduction in needle deflection. CONCLUSION: The factor that most greatly affects the path taken by a needle through a tissuelike substance is the force vectors that act on the needle's beveled surface. The use of a bidirectional rotation insertion technique minimized needle deflection, resulting in a straighter tracking path for 30-, 27-, and 25-gauge dental needles, in 3 different tissuelike substances tested in this study. PMID- 11203905 TI - A pilot study of 2 methods for control of dental unit biofilms. AB - OBJECTIVE: This pilot study was conducted to clinically evaluate 2 different concentrations of sodium hypochlorite for the control of dental unit biofilms and to evaluate the efficacy of pasteurizing dental treatment water for patient care. METHOD AND MATERIALS: Two dental units with no prior chemical treatment were retrofitted with self-contained water systems for this study. One dental unit was treated with 5,000 ppm of sodium hypochlorite and the other with 1,500 ppm. Treatment consisted of a 10-minute contact with the dental unit water lines, followed by a flush with a buffer solution. A pasteurizer was equipped with autoclavable spigots to provide dental treatment water. Heterotrophic Plate Count Samplers (Millipore) water sampler kits were used to quantify microbial contamination as absolute colony-forming units per millimeter. Scanning electron micrographs were taken of water line lumens to compare pretreatment and posttreatment biofilms. RESULTS: Pasteurized water was significantly less contaminated than was tap water. No significant difference in contamination was found between the 5,000 ppm and 1,500 ppm treatment chairs, either in the reservoir water or effluent water. Scanning electron micrographs demonstrated removal of the biofilms after sodium hypochlorite treatments, regardless of the concentration used. CONCLUSION: There was no significant difference between the abilities of 5,000- and 1,500-ppm concentrations of sodium hypochlorite to control contamination of dental treatment water and biofilms. Pasteurization of tap water can reduce contamination; this water can be used as acceptable dental treatment water (< 200 CFU/mL). PMID- 11203906 TI - Conventional cross-sectional tomographic evaluation of mandibular third molars. AB - OBJECTIVE: The purpose of this study was to locate the mandibular canal in relation to the impacted mandibular third molar by conventional cross-sectional tomography. METHOD AND MATERIALS: Conventional axially corrected cross-sectional tomograms of 347 successive impacted mandibular third molars of 234 patients referred for removal of the impacted teeth were acquired with a Scanora x-ray unit. The images were assessed for location of the mandibular canal and the impacted mandibular third molar. Descriptive analysis was performed. RESULTS: Examination of the tomograms revealed the alveolar nerve to have, in relation to the mandibular third molar, a lateral (buccal) course in 53.6% (n = 186), a course between the roots in 26.8% (n = 93), a lingual course in 13.0% (n = 45), and an inferior course in 6.0% (n = 21). Supplementary canals were found in 6.3% (n = 22). Two of the tomograms (0.6%) could not be evaluated, in 1 case because of incorrect patient positioning, resulting in an incorrectly adjusted transverse cut, and in the other case because of a mandibular carcinoma. CONCLUSION: Conventional axially corrected cross-sectional tomograms offer additional information in cases where there is a close relationship between impacted third molars and the alveolar nerve (superimposition of the roots and the canal, grooving, or a varied direction of the canal on the panoramic radiograph) and may contribute to a higher level of intrasurgical safety. PMID- 11203907 TI - Cumulative effects of successive restorative procedures on anterior crown flexure: intact versus veneered incisors. AB - OBJECTIVE: When successive restorative procedures (e.g., porcelain veneers, interdental resin composite restorations, and endodontic treatment) are carried out on the same tooth, significant effects on crown flexure can be expected. METHOD AND MATERIALS: Dentin-bonded porcelain veneers (experimental group) were assessed in vitro using functional and cyclic thermal loads. They were compared to natural teeth (control group) with respect to 2 parameters: coronal flexure (investigated using experimental strain gauges) and morphology of the tooth restoration interface (scanning electron microscopic evaluation). For both veneered and natural teeth, crown deformation was recorded at 5 sequential experimental steps: intact tooth (baseline), Class III cavities, Class III resin composite restorations, endodontic treatment, and endodontic restoration (without posts). RESULTS: No significant differences in crown flexure were found between natural and veneered incisors when compared across experimental steps. The main effect for experimental steps was highly significant. When averaged across all specimens (natural and veneered teeth), the endodontic treatment step resulted in the highest crown flexure (1.55x the baseline value). The unrestored Class III cavities and the endodontic restoration were next highest (1.30x and 1.28x the baseline value, respectively). The lowest crown flexures were found after restoration of the Class III cavities (1.13x the baseline value). No measurable microleakage or gaps were detected at the ceramic-resin, resin-enamel, or resin dentin interfaces (Optibond FL, Kerr). CONCLUSION: Each subsequent reduction in tooth structure resulted in a substantial increase in crown flexibility, even after restoration. Endodontic procedures were responsible for most of the loss in crown stiffness. Extensive proximal cutting and restorations seemed to minimally affect crown flexure. Porcelain veneers showed perfect biomimetic behavior, because cumulated restoration procedures had the same effect on natural and veneered incisors. PMID- 11203908 TI - Subpontic osseous hyperplasia: a case report. AB - Subpontic osseous hyperplasia is an ectopic growth of bone occurring on the edentulous ridge beneath a fixed partial denture replacing a mandibular first molar. A 56-year-old woman experienced an enlargement of the hard and soft tissues beneath the pontic region of a fixed partial denture replacing her mandibular left first molar. Following removal of the fixed partial denture, the bony enlargement was surgically removed, and the bony fragments were submitted for histologic analysis, which demonstrated mature lamellar bone and appositional growth. One year postoperatively, there has been no recurrence of the lesion. The possible etiologies and treatment modalities are reviewed and a rationale for treatment is presented. PMID- 11203909 TI - Clinical images in oral medicine. Encephalotrigeminal syndrome (Sturge-Weber disease). PMID- 11203910 TI - The most important impression: emotional comfort. PMID- 11203911 TI - Behcet's disease: dental and oral soft tissue complications. AB - Behcet's disease is a chronic, multisystem disorder. It has 3 primary components: recurrent inflammations of the eye, ulcerations of the oral mucous membranes, and ulcerations of the genitalia. Diagnosis of Behcet's disease relies mainly on history taking and clinical manifestations. This article describes the oral soft tissue and dental complications and the prosthetic problems encountered in a young patient. If dentists encounter patients with chronic ocular inflammations and recurrent oral mucous membrane ulcers, the index of suspicion should increase. PMID- 11203912 TI - The effect of salt-containing dentifrices on gingival inflammation. AB - OBJECTIVE: This study examined the effect of an alkaline, salt-containing toothpaste, a toothgel of similar contents, and a conventional toothpaste on gingival inflammation. METHOD AND MATERIALS: One hundred fifteen patients suffering from mild to moderate chronic gingivitis were enrolled in a double blind clinical study. All subjects had at least 20 teeth, probing depths of less than 6 mm, and a sulcular bleeding index of 50% or more. At the beginning of the study period, the subjects were randomly assigned to 3 study groups. The baseline examination recorded the number of decayed, missing, and filled teeth, an approximal plaque index, a sulcular bleeding index, and the gingival index. RESULTS: After an 8-week study period, statistically significant reductions in the plaque and bleeding indexes were observed in all 3 groups. There were no significant differences among the 3 dentifrices examined. CONCLUSION: The effectiveness of salt-containing dentifrices in patients with gingivitis was comparable to that of a conventional toothpaste. PMID- 11203913 TI - A comparative study of 2 fluoride-based mouthrinses. AB - OBJECTIVE: The purpose of this study was to compare the effectiveness of 2 mouthrinses (conventional Meridol and alcohol-free Meridol). METHOD AND MATERIALS: A controlled, single-blind clinical study of 3 weeks' duration was conducted on 80 adult subjects in good general health and without severe periodontitis (probing depths no deeper than 4 mm). The mouthrinses supplemented regular measures of oral hygiene for the reduction of plaque and gingivitis. In preliminary examinations to determine general conditions of oral health, especially the level of plaque, gingivitis, and periodontal findings, the approximal plaque index, sulcular bleeding index, and gingival index were established for each subject. Afterward the subjects were provided with a professional toothcleaning, as required. Each subject was randomly provided with 1 of the 2 mouthrinses, to be used 3 times daily in addition to routine oral health measures. The 3 indexes were reevaluated after 3 weeks; in addition, an optional stain index was employed. RESULTS: In both subject groups, a statistically significant reduction in plaque accumulation, as well as a reduction in inflammation and the tendency to bleeding, was observed. Reversible staining of the teeth and tongue was observed in fewer than one third of the subjects in both groups. CONCLUSION: Comparison of the 2 Meridol mouthrinses revealed no difference in effectiveness related to the alcohol content. PMID- 11203914 TI - Use of an existing post to rerestore an endodontically treated tooth with a new post-and-core complex and crown: a case report. AB - Replacement of a post-and-core restoration that has failed because of caries or fracture presents a restorative challenge to the general dentist. This case report describes a new technique that enables the utilization of an unremovable preexisting post in the fabrication of a new post-and-core complex. This complex served as a foundation for a restoration that restored form and function to the patient's dentition. PMID- 11203915 TI - Crown fractures: effectiveness of current enamel-dentin adhesives in reattachment of fractured fragments. AB - OBJECTIVE: The introduction of the current enamel-dentin adhesives has simplified the reattachment of fractured dentinal fragments. The objective of this study was to determine the strength needed to detach coronal fragments reattached with the most recent adhesives. METHOD AND MATERIALS: A complete coronal fracture was caused on the incisal one third of 40 noncarious maxillary and mandibular lateral and central incisors. Each fractured coronal fragment was reattached to its tooth with the enamel-dentin adhesive Scotchbond MP, All-Bond 2, Dentastic, or One-Step (10 specimens each). RESULTS: There was no statistically significant difference between 2 similar fourth-generation adhesives that use orthophosphoric acid as etchant (Dentastic and All-Bond 2) and a fourth-generation adhesive that uses maleic acid as etchant (Scotchbond MP). The values obtained with the fifth generation adhesive (One-Step) were significantly inferior to those obtained with the other 3 enamel-dentin adhesives. CONCLUSION: In the reattachment of fractured tooth fragments, fourth-generation adhesives can guarantee a bonding force stronger than fifth-generation adhesives. PMID- 11203916 TI - Intramuscular hemangiomas. PMID- 11203917 TI - Anesthesia technique needs more testing. PMID- 11203918 TI - Direct pressure provisionalization technique: a new open-tray technique for complete-arch rehabilitations. AB - An innovative direct technique that improves the accuracy of provisional acrylic resin restorations is introduced. A custom impression tray is modified to facilitate complete occlusal closure. This open tray is used to make an accurate overimpression prior to beginning tooth preparation procedures. Following tooth preparation, the acrylic resin-filled overimpression is returned to its intraoral position, and the patient occludes into the previously indexed impression material. The pressure overimpression technique is offered as an expedient technique for improving the accuracy of provisional restorations. PMID- 11203919 TI - Recurrent aphthous stomatitis. AB - Etiology and Epidemiology: The Greek term aphthai was initially used in relation to disorders of the mouth and is credited to Hippocrates (460-370 BC). Today, recurrent aphthous ulceration, or recurrent aphthous stomatitis (RAS), is recognized as the most common oral mucosal disease known to human beings. Considerable research attention has been devoted to elucidating the causes of RAS; local and systemic conditions, and genetic, immunologic, and infectious microbial factors all have been identified as potential etiopathogenic agents (Table 1). However, to date, no principal etiology has been discovered. Epidemiologic studies indicate that the prevalence of RAS is between 2% and 50% in the general population; most estimates fall between 5% and 25%. In selected groups, such as medical and dental students, it has been observed with a frequency as high as 50% to 60%. The peak age of onset for RAS is between 10 and 19 years. After childhood and adolescence, it may continue throughout the entire human lifespan without geographic or age-, sex-, or race-related preference. PMID- 11203920 TI - To treat, or not to treat. PMID- 11203921 TI - Assuring restorative integrity in extensive posterior resin composite restorations: pushing the envelope. AB - Clinicians are increasingly being called on to satisfy the restorative demands of patients who request tooth-colored restorations but are unable to afford an optimum indirect restorative option. Consequently, in clinical practice, the limits of the direct posterior resin composite technique are being stretched. There is a need for techniques that will satisfy the complex variables of clinical practice and allow for successful utilization of posterior resin composite in large cavity preparations. The objective of this article is to explain the rationale behind the materials and techniques involved in the delivery of these complicated restorations. PMID- 11203922 TI - Secondary caries: a literature review with case reports. AB - The clinical diagnosis of secondary caries is by far the most common reason for replacement of restorations, but the scientific basis for the diagnosis is meager. The purpose of this article is to review the literature on secondary (recurrent) caries and present case reports to document the problems encountered in the clinical diagnosis of secondary caries. The literature on secondary caries was critically reviewed and subdivided into clinical diagnosis, location of secondary lesions, histopathology, microleakage, and microbiology. The case reports included restorations that were scheduled to be replaced because of secondary caries or stained margins of composite restorations. The lesions were photographed preoperatively and postoperatively. Based on the limited literature available, secondary caries appears to be a localized lesion similar or identical to primary caries. It is most often localized gingivally on restorations. Narrow gaps, crevices, ditches, and "microleakage" do not lead to secondary caries, but wide voids may. Secondary caries is difficult to diagnose clinically. Consistency or hardness and discoloration of dentin and enamel are the best parameters. Secondary caries is the same as primary caries located at the margin of a restoration. PMID- 11203923 TI - One-year clinical evaluation of compomer restorations placed in general practice. AB - OBJECTIVE: This study evaluated the in-service performance, after 1 year, of a sample of F2000 compomer restorations placed by 10 general dental practitioners as part of handling evaluation of this material. METHOD AND MATERIALS: Five general dental practitioners who participated in the handling evaluation were asked to cooperate in the 1-year assessment of the restorations. The practitioners were requested to contact patients and inquire if they were willing to attend at a specified time for examination of their restorations by a trained evaluator who would travel to the various practice locations. A total of 84 restorations were presented for examination. The mean age of the restorations at examination was 14 months. The restorations were assessed for anatomic form, marginal adaptation, surface roughness, sensitivity or discomfort, gingival condition, and presence or absence of secondary caries. RESULTS: Eighty-two restorations were intact. No secondary caries was detected. Optimal scores were obtained in a high proportion of the assessments. All patients reported satisfaction with the restorations, both in appearance and surface texture, and no symptoms were reported. CONCLUSION: The F2000 compomer restorations, placed in conjunction with its bonding system in general practice conditions, were found to be performing satisfactorily after 1 year. PMID- 11203924 TI - A new prosthodontic technique for fabricating cement-retained implant-supported prostheses. AB - This article describes a new technique for fabricating cement-retained implant supported prostheses. The technique involves cementation of the prostheses over customized gold cylinders. Access channels are incorporated in the prostheses to allow future access of the gold screws. This technique can be used in various clinical situations to achieve total passive fit of the framework without compromising retrievability. The technique overcomes the problems encountered with other previously advocated methods for constructing such prostheses. In addition, maintenance of the resulting prostheses is uncomplicated. PMID- 11203925 TI - Developing cementoblastoma: case report and update of differential diagnosis. AB - The benign cementoblastoma is a rare odontogenic tumor that tends to occur in the jaws of young people. It is most commonly characterized as a circumscribed radiopaque mass attached to the tooth roots and rimmed by a thin radiolucent zone. Early lesions, however, are radiolucent and can be confused with periapical conditions resulting from nonvital teeth. The tumor is seldom recognized until it produces pain or expansion of the jaw. If the diagnosis is established early, the tooth can be saved by endodontic treatment followed by apical root resection and surgical enucleation of the tumor. This case report documents the origin, development, and unlimited growth potential of a cementoblastoma. Radiographs taken at yearly intervals reveal an initial widening of the periodontal ligament space that grew into a 3-cm mixed radiolucent and radiopaque tumor over a 4-year period. The differential diagnosis and some criteria to help distinguish the cementoblastoma from similar-appearing lesions are reviewed. PMID- 11203926 TI - Effect of xerostomic medications on stimulated salivary flow rate in patients with Sjogren's syndrome. AB - OBJECTIVE: The purpose of this study was to examine the effect of xerostomic medications on the salivary output of patients with Sjogren's syndrome. METHOD AND MATERIALS: Of 62 patients evaluated in this study, 23 were not using medication, and 39 were using between 1 and 6 medications with xerostomic side effect. RESULTS: The mean +/- SEM stimulated parotid output was 0.33 +/- 0.07 mL/min per gland for patients who were not using medication and 0.33 +/- 0.04 mL/min per gland for patients using (1 to 6) medications. Analyses did not reveal a significant difference in salivary output between these groups. The salivary output of patients using various numbers of medications (1 or 2; 3 or 4; 5 or 6) was also compared. Analysis revealed no significant difference in salivary output related to the number of xerostomic medications used. CONCLUSION: The use of xerostomic medications may not necessarily affect stimulated parotid flow rate in patients with Sjogren's syndrome. These results suggested that gustatory stimulation may be adequate to overcome the inhibitory effect induced by xerostomic medications. PMID- 11203927 TI - Effect of 3 medicaments on the dimensional accuracy and surface detail reproduction of polyvinyl siloxane impressions. AB - OBJECTIVE: The purpose of this study was to determine the effect of retraction cord medicaments (aluminum chloride, ferric sulfate, and ferric subsulfate/ferric sulfate) on the dimensional accuracy and surface detail reproduction of polyvinyl siloxane impressions. METHOD AND MATERIALS: Polyvinyl siloxane impressions were made of standardized metal dies (American Dental Association [ADA] specification No. 19) treated with 1 of the 3 retraction cord medicaments. Dimensional accuracy was evaluated by comparing the average length of a line in the impressions to the standard die. Surface detail reproduction was evaluated by viewing the impressions under low-angle illumination at x10 magnification. Reproduction was considered satisfactory if 2 of 3 horizontal lines were reproduced continuously. The dies were also evaluated under the microscope before the impression was made. RESULTS: The medicaments did not significantly effect the dimensional accuracy; mean shrinkage was within ADA guidelines in the treatment groups. All of the medicaments had an adverse effect on surface detail reproduction. These effects were statistically significant compared to the untreated control. CONCLUSION: Although the changes in dimensional accuracy were within ADA guidelines, the surface detail reproduction was modified such that the impression would be considered clinically unacceptable. For optimal results, care must taken to remove all traces of these retraction cord medicaments prior to recording of a polyvinyl siloxane impression. PMID- 11203928 TI - Profiles of professionalism. PMID- 11203929 TI - Enamel etching and glass-ionomer sealants. PMID- 11203930 TI - The axial bevel technique: a new technique for extensive posterior resin composite restorations. AB - The objective of this article is to introduce a new preparation design that utilizes external axial bevels and a resin placement technique that involves selective application of 2 resins of different viscosity to optimize marginal integrity in large Class II restorations. The rationale behind the intricate application of material and procedural manipulations involved in the delivery of these complicated restorations is discussed. PMID- 11203931 TI - Direct pulp capping with a dentin adhesive resin system in children's permanent teeth after traumatic injuries: case reports. AB - Traumatic injuries in the permanent teeth of children and adolescents are one of the most frequent causes of dental treatment. The article presents the use of an enamel and dentin adhesive resin system, Syntac, and resin composite materials, Tetric and Variolink, as materials of choice for direct pulp capping after traumatic pulpal exposure (Ellis Class III). Exposed pulp in 10 patients was covered with Syntac and then Tetric and Variolink after etching of dental tissues with phosphoric acid. The follow-up period was from 12 to 48 months. In 1 patient, the treatment was a failure. In the remaining 9 patients, no signs or symptoms of pulpal inflammation or necrosis were observed during the clinical examination. PMID- 11203932 TI - Design features that may influence bacterial plaque retention: a retrospective analysis of failed implants. AB - OBJECTIVE: The purpose of this study was to conduct a postmortem examination of retrieved failed dental implants to identify design characteristics that may have contributed to premature loss. METHOD AND MATERIALS: Forty-five failed implants retrieved from 40 patients with no significant risk factors for implant failure (e.g., history of smoking or diabetes) were examined by scanning electron microscopy. All implants were placed by general dentists or periodontists in private practice and had functioned for an average of 4 years. RESULTS: Several design features of currently used implants present plaque-retentive areas. Plaque accumulation occurred along the implant-transmucosal abutment interfaces, transmucosal abutment-prosthesis interfaces, implant-prosthesis interfaces, and on surfaces of the abutment, the implant, and the prosthesis. The size of the microgap between the various components, the degree of surface roughness of the restorations and abutments, the exposure of plasma-sprayed coatings and threaded surfaces of implants, and overcontouring of implant restorations contributed to plaque accumulation and provided an ideal environment for bacterial colonization. CONCLUSION: These implant features may be key precipitating or exacerbating factors in the development of peri-implant inflammation, predisposing patients to implant failure. PMID- 11203933 TI - Effects of different exposure values on diagnostic accuracy of digital images. AB - OBJECTIVE: The aim of this in vitro study was to compare the effects of different exposure values on the image clarity of 3 digital radiographic systems and 1 conventional direct-exposure emulsion x-ray film. METHOD AND MATERIALS: Three digital radiographic systems, Digora, RVG, and Sidexis, were compared with the conventional dental x-ray film, Ektaspeed Plus. A medullary bone fragment and human teeth were radiographed with varying voltage, exposure time, and focus receptor distance. Clinical criteria to evaluate image clarity were detail resolution, sharpness, contrast resolution, and artifacts of the different tooth and jaw structures. RESULTS: The optimal exposure times for digital imaging varied between 0.02 and 0.13 seconds and depended on the objects and the imaging systems. Optimal resolution was obtained when a voltage of 60 kV was used. The focus-receptor distance of 33 to 40 cm resulted in the best contrast and sharpness. Digital images did not always provide the detail resolution or sharpness achieved by conventional radiographs. CONCLUSION: The recommended exposure time for digital images amounted to approximately half the time needed for conventional film. Digital images had to be modified by adjusting the contrast and brightness to optimize the visibility of the areas to be diagnosed. PMID- 11203934 TI - Fluoride release from a polyacid-modified resin composite and 3 resin-modified glass-ionomer materials. AB - OBJECTIVES: The purposes of this study were to compare the fluoride ion release from a freshly mixed polyacid-modified resin composite, or "compomer" (Dyract), and 3 resin-modified glass-ionomer cements (Fuji II LC, Photac-Fil, and Vitremer) and to compare the use of 3 units for measuring fluoride release. METHOD AND MATERIALS: Five specimens (3.0 x 2.7 mm) of each material were prepared. The specimens were placed in polypropylene vials with 2 mL of deionized water and stored at 37 degrees C. The solutions were replaced weekly and the levels of fluoride ions were analyzed at days 1, 7, and 30 and subsequently every 28 days for 253 days. Fluoride measurements were carried out using a fluoride ion selective electrode connected to a pH ion-selective electrode meter. Fluoride ion release was measured in parts per million, micrograms per square centimeter, and micrograms per cubic millimeter. RESULTS: Fuji II LC, Photac-Fil, and Vitremer showed high initial release values, which decreased exponentially and then showed a slow decline during the ensuing time. Dyract released significantly less fluoride ions during the first 84 days than did the 3 resin-modified glass ionomer cements and maintained this low level of release throughout the study period. The amounts of fluoride ion release measured at any time interval varied with the units of measurement chosen, but the pattern of release remained the same. CONCLUSION: There was a wide variation in the amounts of fluoride ions released from related products, but the patterns of release were similar and unaffected by the units of measurement used. PMID- 11203935 TI - Biomechanics of cervical tooth structure lesions and their restoration. AB - OBJECTIVE: The purpose of this study was to evaluate photoelastically the effects of a cervical tooth structure lesion and its restoration on stress distribution within a tooth. METHOD AND MATERIALS: Three-dimensional composite models of a maxillary first premolar with a buccal cervical lesion were fabricated. Two types of cervical lesion were tested: one was wedge shaped and had a sharp line angle at the apex of the lesion, and the other was more rounded and saucer shaped. Vertical loads of 10 lb were applied to the unrestored and restored models at the tip of the buccal cusp, the tip of the lingual cusp, and the center of the occlusal surface. The resulting stresses within the tooth model were monitored and recorded photographically in the field of a circular polariscope arrangement. RESULTS: In the unrestored situation, stress concentrated at the apex of the lesion, regardless of the lesion configuration. However, the sharper, wedge shaped lesion demonstrated a more severe stress concentration. In the restored situation, stress around the lesion apex and the lingual cervical lesion decreased, while stresses at the gingival and occlusal margins of the lesion increased, compared with the unrestored situation. These tendencies were most obvious when the buccal cusp was loaded. CONCLUSION: The presence of a cervical lesion changed occlusal load-induced stress distribution and concentrated stress at the apex of the lesion. The shape and dimension of the lesion governed the severity of stress concentration. Restoration of the cervical lesion relieved concentrated stress at the apex of the lesion. PMID- 11203936 TI - Clinical indications for altering vertical dimension of occlusion. Functional and biologic considerations for reconstruction of the dental occlusion. PMID- 11203937 TI - Clinical indications for altering vertical dimension of occlusion. Objective vs subjective methods for determining vertical dimension of occlusion. PMID- 11203938 TI - Kaposi's sarcoma. PMID- 11203939 TI - Periodontics: the hub around which the rest of dentistry turns. PMID- 11203940 TI - Clinical evaluation of bleaching agents of different concentrations. AB - OBJECTIVE: The purpose of this study was to evaluate the degree of color change, any rebound effect, and sensitivities associated with using 2 different concentrations of carbamide peroxide in vivo. METHOD AND MATERIALS: Twenty-five subjects used 10% and 15% agents in trays for 14 days on different sides of their maxillary arches. Subjects returned in 3 days and at 1, 2, 3, and 6 weeks for evaluation of color change and rebound effect. Shade matching, photographic means, and a colorimeter were used for evaluation. Subjects self-reported gingival and tooth sensitivity on a scale of 1 (no sensitivity) to 5 (severe sensitivity). RESULTS: After 2 weeks, delta L*, delta a*, delta b*, delta E* and delta shade guide rank means for the 10% whitening agent were 6.50, -1.37, -4.63, 8.79, and -15.40, respectively; for the 15% agent, they were 8.72, -1.63, -5.90, 11.03, and -16.59, respectively. After 6 weeks, delta L*, delta a*, delta b*, delta E*, and delta shade guide rank means for the 10% whitening agent were 3.04, -0.99, -3.19, 5.13, and -13.13, respectively; for the 15% agent, they were 3.48, 1.01, -3.60, 5.58, and -13.65, respectively. Means for gingival sensitivity were 1.18 and 1.21 for the 10% and 15% agents, respectively; means for tooth sensitivity were 1.21 and 1.26 for the 10% and 15% agents, respectively. CONCLUSION: All 3 methods of evaluation revealed a significant difference in the tooth lightness achieved by 10% and 15% products at 2 weeks but no significant difference at 6 weeks. No statistically significant difference was found in gingival or tooth sensitivity. PMID- 11203941 TI - Extracoronal resilient attachments in distal-extension removable partial dentures. AB - Esthetics is often compromised in patients who wear removable partial dentures with metal clasps placed on anterior teeth. Clinical procedures are presented for a new design of a removable partial denture that improves esthetics and function through a new dental attachment. The extracoronal resilient attachment system offers vertical resiliency and universal stress relief for use where a resilient prosthesis is indicated. The removable partial denture retained by these attachments provides esthetics, vertical resiliency, and easy replacement of worn attachments. PMID- 11203942 TI - A preliminary comparative study of the guided tissue regeneration and free gingival graft procedures for adjacent facial root coverage. AB - OBJECTIVE: The purpose of this study was to compare the clinical efficacy of guided tissue regeneration with expanded polytetrafluoroethylene membranes to that of free gingival graft for treatment of adjacent facial gingival recession. METHOD AND MATERIALS: Eight adjacent gingival recession sites with Miller class I or II defects containing at least a maxillary or mandibular canine were selected in 6 patients. Four recession sites in 3 patients were treated with guided tissue regeneration, and the other 4 sites in the remaining 3 patients were treated with free gingival graft. Probing depth, gingival recession, attachment level, width of keratinized gingiva, and root coverage were recorded before surgery (baseline) and 6 months and 1 year postoperatively. RESULTS: Statistically significant improvements were found for gingival recession, attachment level, and root coverage from baseline to 6 months and 1 year postoperatively in both groups. Both procedures produced the same average reduction in gingival recession, gain in attachment level, and amount of root coverage after 1 year. Probing depths did not differ between groups throughout the study. The width of keratinized gingiva was significantly greater in the grafted group than in the guided tissue regeneration group. CONCLUSION: Both procedures produced the same average amount of root coverage, reduction in gingival recession, and gain in clinical attachment. The guided tissue regeneration procedure provided a better esthetic appearance without any difference in gingival color or architecture in cases of adjacent facial gingival recession. PMID- 11203943 TI - Intrusion injuries of primary incisors. Part I: Review and management. AB - Intrusion injuries commonly occur in the primary dentition. They can be described as luxation injuries resulting from an axially directed impact, which drives the tooth deeper into the alveolar socket. The impact results in compression of and damage to the periodontal ligament as well as injury to the pulp of the intruded incisor. In addition to rendering treatment to the intruded primary tooth, the dentist must also be aware of the possibility of an injury to the developing permanent teeth germs located in close proximity to the roots of the injured primary teeth. This review will discuss the characteristics, implications, and management of intrusion injuries of primary incisors. PMID- 11203944 TI - Intrusion injuries of primary incisors. Part II: Sequelae affecting the intruded primary incisors. AB - Luxation injuries to incisors, including intrusive displacement, occur with a high frequency in the primary dentition. Intrusion injuries are associated with damage to the pulpal and periodontal structures and possible fracture of the alveolar bone. The pulpal tissue of the intruded tooth sustains a severe shock during displacement, which may be reflected later by sequelae ranging from mild discoloration to pulpal necrosis and infection. Disintegration of pulpal tissue may result in periapical tissue inflammation, which in turn may induce developmental disturbances in the germ of the permanent successor tooth. Additionally, severe injury to the periodontal ligament during intrusion may lead to ankylosis of the primary incisor and consequently to delayed or ectopic eruption of its permanent successor. This article will review the possible sequelae affecting primary incisors following their intrusion. PMID- 11203945 TI - Treatment of a palatal groove-related periodontal bone defect. PMID- 11203946 TI - A comparison of the marginal and internal adaptation of amalgam and resin composite restorations in small to moderate-sized Class II preparations of conventional design. AB - OBJECTIVE: The purpose of this study was to compare the marginal and internal adaptation of a non-gamma-2 amalgam and an ultrafine compact-filled light-cured composite in small to moderate-sized Class II restorations of conventional design. METHOD AND MATERIALS: Fifty recently extracted human premolar and permanent molar teeth were selected for the study. The teeth were restored with either a non-gamma-2 amalgam alloy or a light-cured resin composite. The marginal adaptation of the restorative materials to the proximal surface outline form of each preparation was assessed. The mean percentages of perfect margins, marginal fissuring, and underfilled margins for the 2 restorative materials were recorded and statistically analyzed. RESULTS: Both materials performed equally well in the buccal and lingual segments of the proximal box. At the cervical margin, the resin composite restorations showed a significantly greater number of imperfect margins and marginal fissuring. The incidence of underfilled margins was low for both restorative materials even at the cervical margin. CONCLUSION: Although there was some cause for concern about the marginal adaptation of the resin composite restorations along the cervical margin, the findings support contemporary teaching that small to moderately sized conventional Class II preparations may justifiably be restored with an appropriate resin composite. PMID- 11203947 TI - Bond strengths of nonrinsing adhesives. AB - OBJECTIVE: The purpose of this study was to determine enamel and dentin bond strengths of a nonrinsing "all-in-one" adhesive and of a nonrinsing conditioner combined with a 1-bottle adhesive. METHOD AND MATERIALS: Specimens were obtained from 240 bovine teeth ground to expose enamel or dentin surfaces. Ten enamel and 10 dentin specimens were randomly assigned to each of 12 different combinations of adhesive system (Prompt L-Pop; no etch + Prime & Bond NT; NRC + Prime & Bond NT; 36% phosphoric acid + Prime & Bond NT; no etch + Prime & Bond 2.1; 36% phosphoric acid + Prime & Bond 2.1) and restorative material (resin composite; polyacid-modified resin composite ["compomer"]). After the application of the adhesive system, a No. 5 gelatin capsule filled with the restorative material was seated against the enamel or dentin surface. After 24 hours in distilled water at 37 degrees C, the specimens were thermocycled and the shear bond strengths were measured. RESULTS: For resin composite, etching with phosphoric acid resulted in the highest bond strengths to enamel. For compomer, the highest enamel bond strengths were achieved with both phosphoric acid and Prompt L-Pop. Treating dentin with Prime & Bond NT without etching provided the highest mean bond strength for composite. For compomer, treating dentin with Prime & Bond NT resulted in the highest mean bond strengths, regardless of the conditioner. CONCLUSION: Compomer and resin composite exhibited statistically similar bond strengths. Bond strengths to dentin were significantly lower than those to enamel. PMID- 11203948 TI - Oral lesions secondary to fellatio. PMID- 11203949 TI - Improving dentist-patient relations. PMID- 11203950 TI - Dentoalveolar trauma: can you manage it? PMID- 11203951 TI - Infection control. PMID- 11203952 TI - Classification for minimal intervention. PMID- 11203953 TI - Intrusion injuries of primary incisors. Part III: Effects on the permanent successors. AB - Intrusion injuries of the primary dentition are highly associated with developmental disturbances of their successor teeth. The age of the child at the time of injury, the direction and severity of the intrusion, and the presence of alveolar bone fracture are important variables influencing the effect of primary tooth intrusion on the developing permanent germ. The developmental defects of the permanent successor tooth range from mild alteration in enamel mineralization to severe sequestration of the developing germ. This article will review the developmental anomalies of the permanent incisors induced by intrusion injuries of their predecessors. PMID- 11203954 TI - Clinical considerations for reattachment of tooth fragments. AB - Trauma to anterior teeth is relatively common among children and teenagers; it has been estimated that approximately one quarter of the population under the age of 18 years sustain traumatic injury in the form of anterior crown fracture. Reattachment of a fractured fragment to the remaining tooth can provide esthetically pleasing results provided that the fragment is available. In this report, a systematic clinical approach through evaluation of periodontal, endodontic, coronal, and occlusal aspects is presented to help dentists analyze the factors affecting selection of techniques and materials. In addition, use of adhesive materials for tooth fragment reattachment is illustrated. Modifications of the reattachment process, including placement of veneer and radicular post, are also discussed. PMID- 11203955 TI - A modified indirect working die technique for fabricating provisional restorations for multiple teeth. AB - The "modified" indirect working die technique is introduced. The technique expands the capabilities of the indirect working die technique, which features flexible removable dies for fabricating provisional restorations. The modified technique is distinguished by its potential for restoring multiple teeth, up to and including the complete arch, by utilizing a complete-arch impression tray to which a simple modification is made. It is an accurate, timesaving, and laborsaving method for fabricating provisional restorations. PMID- 11203956 TI - Amelogenesis imperfecta: functional and esthetic restoration of a severely compromised dentition. AB - The treatment of patients with severe forms of amelogenesis imperfecta presents an interesting challenge to the dental team. A 16-year-old girl presented with a severely compromised occlusion and poor esthetics that had lowered her self esteem. Preoperative investigations included the determination of completion of growth, an accurate diagnostic waxup, and an evaluation of clinical crown lengths. Periodontal full-flap surgery was planned to lengthen clinical crowns and create gingival harmony. This was to be followed by placement of 28 complete crowns to restore occlusal function and gain a pleasing esthetic result. All porcelain crowns were placed from premolar to premolar in each arch (20 crowns), and porcelain-fused-to-metal crowns were placed on each molar tooth in each arch (8 crowns). The final treatment result provided this patient with a mutually protective occlusion and with esthetics that greatly enhanced her self-image. PMID- 11203957 TI - Biologic restoration of primary anterior teeth. PMID- 11203958 TI - Overgrowth of a costochondral graft in temporomandibular joint reconstructive surgery: an uncommon complication. AB - A 16-year-old girl had a history of unilateral ankylosis of the temporomandibular joint, which was reconstructed with an autogenous costochondral graft. About 2.5 years after surgery, the patient presented with overgrowth of the costochondral graft, resulting in deviation of the jaw toward the unaffected side. PMID- 11203959 TI - Hereditary gingival fibromatosis: review of the literature and a case report. AB - Hereditary gingival fibromatosis is a proliferative fibrous lesion of the gingival tissue that causes esthetic and functional problems. Both genetically and pharmacologically induced forms of gingival fibromatosis exist. This paper reports a case of severe generalized hereditary gingival fibromatosis in a 5-year old girl. Treatment consisted of surgical removal of the hyperplastic fibrous tissue in a series of conventional gingivectomies. Postoperative examination 36 months after the final procedure revealed no signs of recurrence. PMID- 11203960 TI - Frequency of oral manifestations in children infected with human immunodeficiency virus. AB - OBJECTIVE: The main objective of this study was to investigate the frequency of oral manifestations in children with acquired immunodeficiency syndrome. It also attempted to correlate the presence of lesions with the patient's degree of immunosuppression, as measured by the T4/T8 ratio. METHOD AND MATERIALS: Oral examinations were performed in 51 children with acquired immunodeficiency syndrome for a 2-year period. A questionnaire used in this investigation was based on the children's classification proposed by the Centers for Disease Control in 1987. The children's T4/T8 ratios were obtained from their medical files. RESULTS: Pseudomembranous candidiasis was the most common lesion, found in 21.57% of the children. Salivary gland disease was present in 19.61% of patients. Erythematous candidiasis was observed in 5.88%, and linear gingival erythema and oral hairy leukoplakia were both observed in 1.96% of children. Children with a T4/T8 ratio < 0.5 were more prone to development of pseudomembranous candidiasis. CONCLUSION: Pseudomembranous candidiasis was the most common type of oral lesion in human immunodeficiency virus-positive children with acquired immunodeficiency syndrome. There was a relationship between the frequency of oral manifestations and the patient's T4/T8 ratio. PMID- 11203961 TI - Quality assessment of marginal sealing using 7 dentin adhesive systems. AB - OBJECTIVE: The goal of this investigation was to assess in vitro the quality of marginal sealing of composite-dentin adhesive systems and human dentin. METHOD AND MATERIALS: Forty intact human premolars and third molars were extracted from subjects of both sexes and of different ages. After the enamel layer was removed, a Class V cavity was formed on the buccal surface, and a wedge cavity was formed on the lingual surface. These were restored with resin composite materials and their corresponding dentin adhesive systems. The quality of marginal sealing was evaluated by assessing the linear penetration of silver nitrate dye. RESULTS: The best marginal sealing between composite materials and the cavity walls, in both wedge erosions and Class V cavities, was provided by Scotchbond Multi Purpose/Valux and Syntac/Helioprogres systems. Dye penetration was slightly greater with the XR-Bond/Herculite, Gluma/Pekafill, and Superlux Universal Bond 2/Superlux Solar systems. The greatest microleakage was observed in Tripton/Opalux and Denthesive/Charisma specimens. CONCLUSION: The use of an adhesive system and the corresponding resin composite does not eliminate microleakage completely when the cavity margins are in dentin. PMID- 11203962 TI - Microleakage of a condensable resin composite: an in vitro investigation. AB - OBJECTIVE: The purpose of this investigation was to evaluate microleakage in Class II cavities restored with the condensable resin composite SureFil, placed with or without a liner and 1 of 2 different dentin bonding agents. METHOD AND MATERIALS: Extracted noncarious human teeth were randomly divided into 4 groups of 15 each and restored according to manufacturer's instructions: group 1, SureFil and Prime & Bond NT; group 2, SureFil and PQ1; group 3, SureFil, PermaFlow, and PQ1; group 4, Heliomolar and Syntac Single-Component (control). Specimens were stored in 37 degrees C water for 24 hours. All specimens were thermocycled between 5 degrees C and 55 degrees C for 500 cycles. Each specimen was immersed in 0.2% basic fuchsin dye for 24 hours and then sectioned longitudinally and horizontally. Dye penetration at enamel and cementum margins were viewed at x30 magnification by 2 independent, calibrated evaluators. Specimens exhibiting dye penetration > or = 0.1 mm beyond the cavosurface margin were considered to have leakage. RESULTS: Chi-square tests revealed no statistically significant differences in the presence of microleakage when all groups were analyzed together. However, 2 by 2 comparisons revealed that group 3 had significantly fewer specimens with microleakage than did group 1, 2, or 4. CONCLUSION: To limit microleakage, a flowable composite should be used as a liner when a condensable composite material is used. PMID- 11203963 TI - Simple ways to reduce patient anxiety. PMID- 11203964 TI - Pyogenic granuloma (pregnancy tumor). PMID- 11203965 TI - Dentistry's social responsibility: the persistent voice. PMID- 11203966 TI - Tunnel restorations placed in routine practice and observed for 24 to 54 months. AB - OBJECTIVE: The purpose of this study was to evaluate the feasibility and performance of tunnel restorations placed in routine public dental service. METHOD AND MATERIALS: A total of 420 small approximal lesions received tunnel restorations 12 general practitioners. Three hundred two restorations in 179 patients were available for evaluation after a minimum period of 24 months. The restorations were evaluated by modified US Public Health Service criteria. RESULTS: After service periods up to 54 months, 57% of the restorations were found to be clinically and radiographically acceptable. The remainder had already been replaced or were assessed as unacceptable. High levels of carious activity and internal-type preparations resulted in the poorest prognosis. The success rates varied considerably among the operators, but these differences did not reach statistical significance. CONCLUSION: The indications for use of the tunnel restoration technique for the treatment of primary approximal lesions seem to be limited at present. Partial tunnel restorations may have a somewhat better prognosis than the internal tunnels, but high carious activity has a detrimental effect. Tunnel restorations may be considered for particularly cooperative patients with a low caries rate as a semipermanent treatment for small lesions. PMID- 11203967 TI - Cervical dentin hypersensitivity. Part I: The air indexing method. AB - The purpose of this article is to introduce an objective method for quantifying cervical dentin hypersensitivity. Air emissions from a standard air-water syringe or a syringe with a Fluid Control Block are directed toward the cervices of teeth at a 45-degree angle to the long axis of test teeth from a distance of 0.5 cm for 0.5 to 1.0 second. An air indexing method has been developed to quantify threshold patient response values for individual teeth to this defined air stimulus. The air indexing method, using the Fluid Control Block, offers the clinician objective information to compare cervical dentin hypersensitivity before and after treatment for this common, painful condition. PMID- 11203968 TI - Cervical dentin hypersensitivity. Part II: Associations with abfractive lesions. AB - OBJECTIVE: The purpose of this retrospective study was to evaluate the association between cervical dentin hypersensitivity and the presence of abfractive lesions. METHOD AND MATERIALS: Written records and study casts for 250 active-care patients, selected alphabetically, were analyzed for the clinical detection of abfractive lesions and cervical dentin hypersensitivity from 1979 until 1996. Clinical diagnosis of abfractive lesions was made according to existing literature descriptions of these hard tissue lesions. Cervical dentin hypersensitivity was diagnosed when a verified positive threshold patient response was found during tooth evaluation by the air indexing method. Patient groups I and II were formed solely on the basis of the presence or absence, respectively, of a verified positive threshold patient response of cervical dentin to air. RESULTS: A significant association was found between air-indexed cervical hypersensitivity and the presence of abfractive lesions. The primary locations for both cervical hypersensitivity and abfractive lesions were the buccal surfaces of posterior teeth. CONCLUSION: This long-term retrospective study found a positive association between cervical dentin hypersensitivity and abfractive lesions. The correlative nature of this study suggests the need for further investigation. PMID- 11203969 TI - An alternative hypothesis from veterinary science for the pathogenesis of noncarious cervical lesions. AB - An alternative hypothesis to abrasion and erosion for the pathogenesis of noncarious cervical lesions was put forward in 1984; the so-called occlusal theory suggested that tensile stresses from occlusal overload could be involved in the pathogenesis of noncarious cervical lesions and that bending stresses applied to teeth could cause disruption of the surface enamel, resulting in increased susceptibility to dissolution and abrasion at the affected sites and in the development of wedge-shaped lesions. This theory has gained increased acceptance in recent years, although absolute scientific evidence has been scant. These lesions also occur in animals, in particular, the domestic cat, in which they are called feline odontoclastic resorptive lesions. A variety of theories about pathogenesis of these lesions have been put forward, but there is some evidence that occlusal overload may be a contributory factor in the development of an inflammatory response in the periodontal membrane and the presence of enzymes associated with resorption in the gingival crevice. Further investigation may help define a common etiology between the pathogenesis of feline odontoclastic resorptive lesions and noncarious cervical lesions. PMID- 11203970 TI - Soft tissue management in oral implantology: a review of surgical techniques for shaping an esthetic and functional peri-implant soft tissue structure. AB - Along with osseointegration and restoration of function, the patient's subjective satisfaction with the esthetic result is a touchstone of the success of implant therapy. Although esthetic restoration of natural teeth can be achieved routinely through appropriate tooth preparation and a natural-looking design on the part of the dental laboratory, the road to success is much more complicated with implants, because of atrophy of bone and mucosa. Surgical techniques, paths of incision, and useful instruments for implant therapy are described, from implant placement to exposure. These methods help to provide durable, functional, and esthetic results. PMID- 11203972 TI - Dental restorations: choose carefully. PMID- 11203971 TI - Shear bond strength, microleakage, and confocal studies of 4 amalgam alloy bonding agents. AB - OBJECTIVE: This study was undertaken to determine the relative shear bond strengths and microleakage of 4 bonding agents to dentin and amalgam and to investigate the bonding to dentin through confocal laser scanning microscopy. METHOD AND MATERIALS: Sixty noncarious molars were restored with 1 of 4 different systems, and the shear bond strengths were determined. For the microleakage study, Class V amalgam restorations were placed in 60 noncarious teeth. The specimens were thermocycled, the teeth were sectioned, and dye penetration was assessed. For confocal examinations, the first component of the bonding adhesives was labeled with rhodamine B. Each of the adhesives was applied to 3 dentin specimens, which were examined under a confocal laser scanning microscope RESULTS: Of the 4 restorative systems tested, AmalgamBond Plus + HPA and Prime & Bond 2.1/base-catalyst showed significantly higher shear bond strengths. Prime & Bond 2.1/base-catalyst had the lowest microleakage value, which was significantly lower than that of AmalgamBond Plus + HPA and AmalgamBond Plus. AmalgamBond Plus + HPA had the highest variation in both the bond strength and microleakage values. Confocal laser scanning microscopy revealed tag formation, penetration of the bonding agents deep into the tubules, and hybrid layer formation for all 4 bonding systems. CONCLUSION: The 2 best systems, Prime & Bond 2.1/base-catalyst and, to a lesser extent, AmalgamBond Plus + HPA, utilized a supplemental bonding agent. PMID- 11203973 TI - Minimal intervention: a new concept for operative dentistry. AB - The term minimal intervention is relatively new in dentistry and has been introduced to suggest to the profession that it is time for change in the principles of operative dentistry. The disease should be treated first; the surgical approach should be undertaken only as a last resort and then with the removal of as little natural tooth structure as possible. This article discusses the advances in techniques and materials that have led to change and attempts to put them into perspective. Treatment should begin with identification and elimination of the disease. There will then be a need for limited restoration of actual cavitation arising from demineralization of the tooth crown. Restorations, per se, will not prevent or eliminate disease. Caries is a bacterial infection and, until the microflora is controlled, all restorations are at risk of further demineralization in remaining tooth structure. This leads to the continuum of replacement dentistry that keeps the profession occupied for much of its productive time. If this cycle is to be broken, the profession must first acknowledge the primacy of prevention. PMID- 11203974 TI - Minimal intervention: early lesions. AB - The use of modified cavity designs for the treatment of initial carious lesions can be justified on the grounds that, because no restorative material can adequately replace natural tooth structure for the long term, preservation of natural tooth structure is important. It is apparent that it is possible to remineralize and heal demineralized tooth structure to some degree. Therefore, neither enamel nor dentin should be removed simply because it has lost calcium and phosphate ions as a result of acid attack. The older surgical approach to cavity design was adopted in the absence of adhesive techniques and on the basis of Black's principle of "extension for prevention," but this theory is no longer tenable. The current availability of adhesive bioactive restorative materials makes it possible to maintain areas of tooth structure even though they appear to be undermined and weakened. Thus, the concept of geometric designs for prescribed cavities is no longer valid. The purpose of this article is to describe a series of simplified, modified cavity designs for small initial lesions; preservation of natural tooth structure is the principle objective of these designs. PMID- 11203975 TI - Bondable reinforcement ribbon: clinical applications. AB - Bondable reinforcement ribbon can be used in dentistry to splint periodontally involved teeth, to provide postorthodontic splinting, to reinforce provisional prostheses, and to fabricate direct adhesive prostheses. Four cases illustrate esthetically and functionally successful use of reinforced ribbon. PMID- 11203976 TI - Esthetic gingival recontouring--a plea for honesty. AB - There continues to be a tremendous amount of confusion in the dental literature and among practitioners regarding the diagnosis and treatment of gingival discontinuities. The purpose of this article is to present a rationale for gingival recontouring, illustrated by a case report. A patient requested gingival recontouring. Because the preoperative evaluation was inadequate, a simple gingivectomy procedure was performed. After healing, the tissue had rebounded to its preoperative levels. The patient was then evaluated more comprehensively, and gingival recontouring was accomplished with a mucoperiosteal flap and osseous recontouring. The tissue subsequently healed at the correct position and remained stable. To reliably perform gingival recontouring procedures, the dentist must have a clear understanding of the biologic width. By using diagnostic bone sounding, the practitioner can determine the appropriate surgical procedure that will ensure an esthetic and stable postoperative result. PMID- 11203977 TI - Direct resin composite veneers: masking the dark prepared enamel surface. AB - A technique for manufacturing direct resin composite veneers is presented. Described are the advantages of using an acrylic resin matrix, made before the preparation is begun, to copy anatomic details. An additional step to mask previously prepared dark enamel with opaquers is also described. The advantages and limitations of the procedures are discussed. PMID- 11203978 TI - Simplified adhesion of compomers in pediatric dentistry. AB - A self-etching adhesive agent for bonding polyacid-modified resin-based composite materials ("compomers") to enamel and dentin is now available. The Prompt L-Pop system simplifies and hastens dental bonding procedures and has proved itself useful in many adhesive dentistry applications. This article describes the bonding system and shows clinical examples of its use in children and teenagers. The concept will have further application in adhesive dentistry with introduction of a new formulation of Prompt, to be used with traditional resin-based composite materials. PMID- 11203979 TI - Resin-modified glass-ionomer restorations and in vitro secondary caries formation in coronal enamel. AB - OBJECTIVE: The purpose of this laboratory study was to compare the effects of a resin-modified glass ionomer and a resin composite restorative material on secondary caries formation in coronal enamel. METHOD AND MATERIALS: Twelve caries free molars were sectioned into tooth quarters. Coronal cavities were prepared and then restored with either a resin-modified glass-ionomer material (mesiobuccal and mesiolingual tooth quarters), or a resin composite (distobuccal and distolingual tooth quarters). Caries like lesions were created, and secondary caries was examined by polarized light microscopy following lesion initiation and progression periods. RESULTS: The resin-modified glass-ionomer specimens had significantly shallower primary surface lesions at both the lesion initiation (35% shallower) and progression (45% shallower) periods than did the resin composite specimens. There were significantly fewer wall lesions (3-fold and 2 fold fewer following lesion initiation and progression, respectively) in the resin-modified glass-ionomer group than in the resin composite group. CONCLUSION: Resin-modified glass-ionomer restorations reduce the susceptibility of unrestored adjacent enamel surfaces and cavosurfaces to a constant cariogenic challenge. The caries resistance imparted to the surface enamel and cavosurface is most likely due to the fluoride release from the resin-modified glass-ionomer material. PMID- 11203980 TI - Pulpotomy reconsidered: application of an adhesive system to pulpotomized permanent primate pulps. AB - OBJECTIVE: This study was undertaken to compare the healing response of permanent primate pulps to pulpotomy procedures following hemorrhage control and adhesive hybridization to their response after conventional treatments. METHOD AND MATERIALS: Forty-two cavities were placed throughout the dentitions of 4 adult monkeys. In 24 teeth, following mechanical bur exposure and pulpotomy, hemorrhage was controlled with application of 3% sodium hypochlorite. The cavity was rinsed and the enamel-dentin-pulp surface was restored with an adhesive system for 6 and 7 months. Calcium hydroxide, formocresol, and resin-modified glass-ionomer cement were placed as conventional treatments in 18 teeth for 70 days and cavities were sealed with resin-modified glass-ionomer cement. Following perfusion fixation, tissues were demineralized, sectioned, stained, and histologically graded using defined criteria. RESULTS: Of 24 adhesive system pulps, 10 showed no or minimal pulpal response, 1 showed an acute response, 6 showed a chronic response, 2 showed a severe response, and 5 showed compartmentalized zones of localized necrosis. Only 8 adhesive system pulps showed stained bacteria associated with inflamed tissues. Thirteen adhesive system pulps showed dentin bridging directly at the adhesive system interface. Calcium hydroxide-treated specimens showed healing and dentin formation, while resin-modified glass-ionomer cement and formocresol treatments failed to result in any bridging. Apical tissues in all adhesive-treated specimens showed normal pulps and primary odontoblasts along their entire walls. CONCLUSION: Permanent pulps without periapical radiolucencies may survive pulpotomy, provided that hemorrhage is properly controlled and the pulp-restoration interface is hybridized to exclude all microleakage. PMID- 11203981 TI - Osteosarcoma. PMID- 11203982 TI - Improving dentist-patient relations. PMID- 11203983 TI - Failure to diagnose: can it happen to you? PMID- 11203984 TI - Treatment option for dentoalveolar trauma. PMID- 11203985 TI - Design principles for cantilevered resin-bonded fixed partial dentures. AB - Recent clinical studies show 2-unit cantilevered resin-bonded fixed partial dentures to be as retentive or more retentive than their fixed-fixed counterparts. The fact that the 2-unit prosthesis is successful adds value to the clinical use of resin-bonded fixed partial dentures because the single-abutment prosthesis is even simpler and more cost effective than fixed-fixed designs. However, there is no evidence-based information relating to design principles for abutment preparation and framework design for the single-abutment, single retainer prosthesis. The aim of this report is to suggest principles of design for the 2-unit cantilevered fixed partial denture, based on information gained from studies on fixed-fixed designs. PMID- 11203986 TI - Minimal intervention: advanced lesions. AB - Minimal intervention techniques are generally considered in relation to initial carious lesions. However, it appears logical to apply the same principles to extensive cavities as well as to the replacement of failed existing restorations. As the cavity becomes larger, there is an increasing need to consider protection of remaining cusps because they become seriously weakened by loss of the central core of the crown and therefore become subject to the development of splits at the base. However, it is possible to develop a protective cavity design without undue sacrifice of remaining tooth structure, at the same time that maintenance of occlusal anatomy and correct contact with the opposing arch are ensured. For larger cavities, special consideration needs to be given to the strength of the restorative material. Glass ionomer is relatively brittle and should not be exposed to undue occlusal load. Resin composites cannot be regarded as universal in their physical properties, and placement is time-consuming. A lamination technique is often useful, combining the advantages of both glass ionomer and resin composite. Amalgam should not be entirely discarded as an option because it has greater strength than both glass ionomer and resin composite and is still useful for the restoration of extensive cavities and for protection and retention of weakened cusps. Minimal intervention principles, designed to limit the loss of natural tooth structure, should be applied to all restorative dentistry. None of the available restorative materials is entirely satisfactory in the long term. PMID- 11203987 TI - Clinical evaluation of polyacid-modified resin composite posterior restorations: one-year results. AB - OBJECTIVE: The aim of this investigation was to evaluate the clinical performance of a new compomer restorative system, Dyract AP, placed in combination with Non Rinse Conditioner and Prime & Bond NT in permanent posterior teeth. METHOD AND MATERIALS: Fifty Class II and 41 Class I restorations were placed in 39 patients by 1 dentist. The restorations were evaluated directly, with modified US Public Health Service criteria, and indirectly, with color slides and polyvinyl siloxane impressions, at baseline and 6 months and 1 year after placement. Preoperative and 1-year postoperative bitewing radiographs were also taken. RESULTS: All 82 restorations available for 1-year evaluation were in situ. No postoperative sensitivity or pulpal problems were reported. Four Class II restorations (4.9%) failed because of partial fracture or recurrent caries. The percentages of Alfa score for each criterion were color match, 95.1%; marginal discoloration, 57.3%; marginal integrity, 35.4%; anatomic form, 98.8%; and surface texture, 91.5%. The average wear rate of Dyract AP was low (18.5 +/- 11.7 microns at 6 months and 35.7 +/- 13.6 microns at 12 months). CONCLUSION: The excellent handling characteristics, the good clinical performance, and the improved wear resistance suggest that this compomer will provide reliable direct tooth-colored restorations in stress-bearing areas. PMID- 11203988 TI - Establishing the differential diagnosis of neck lesions. AB - A thorough physical examination of the head and neck should be included as part of the evaluation of every dental patient. Although they most often represent a self-limited inflammation, a benign neoplasm, or a congenital anomaly, neck lesions can also be malignant. Because the pathologic lesions that can arise in the neck are varied and diverse, the diagnostic thought process should be orderly and inclusive so that a reasonable differential diagnosis can be established and prompt, effective treatment can be rendered. PMID- 11203989 TI - Oral rehabilitation of a hypohidrotic ectodermal dysplasia patient: a 6-year follow-up. AB - This case report describes the oral rehabilitation of a female child with hypohidrotic ectodermal dysplasia over a 6-year time period. It demonstrates the need for periodic modification and replacement of a prosthesis, an orthodontic appliance, and a gingivoplasty. Although the initial treatment plan was considered to be a compromise due to limited cooperation, an improvement was observed in the patient's social behavior as a consequence of her dental treatment. The effects of unavoidable changes in the dental team over 6 years are also discussed. PMID- 11203990 TI - Dental photography in support of patient documentation and communication. AB - Intraoral conditions, which in the course of dental treatment are subject to change, can be recorded in detail by means of photography. Pictures provide an improved documentation and the option of monitoring particular situations over longer periods of time. We propose a standardized preoperative 35-mm photographic series. For intraoral photography, special intraoral mirrors and lip-and-cheek retractors are modified as needed. Macro 35-mm cameras with macro flash are by now well-established. Such equipment combined with the technique outlined in this report make standardized photographic documentation possible without mouth-angle retractors and mirror rims obstructing the view. PMID- 11203991 TI - Light energy transmission through cured resin composite and human dentin. AB - OBJECTIVE: This study determined the amount of light energy transmitted through various densities of cured resin composite and human dentin when 2 different light intensities were used. METHOD AND MATERIALS: The maximum light energy (mW/cm2) transmitted through disks (0.46 to 5.85 mm thick) of 7 resin composites and human dentin was measured when either a Standard or a Turbo light guide was attached to a curing light. The effects of the 2 light guides, the specimen thickness, and type of specimen dentin on light energy transmission were determined. RESULTS: The mean light energy reading at the surface of the specimens was 682.1 mW/cm2 with the Standard light guide and 1,014 mW/cm2 with the Turbo light guide. For all the specimens, there was an exponential decrease in light energy transmitted as the specimen thickness increased. The analysis of covariance showed that the specimen, thickness, and light guide all had a statistically significant effect. Significantly more light energy (about 42%) was transmitted through the specimens when the Turbo light guide was used. CONCLUSION: When the Turbo light guide was used, about 42% more light energy was transmitted through the cured composite specimens. There was an exponential decrease in the light energy transmitted through 7 resin composites and dentin as the specimen thickness increased. PMID- 11203992 TI - Use of a compomer in Class V restoration: a microleakage study. AB - OBJECTIVE: The purpose of this investigation was to evaluate the microleakage of Class V lesions restored with a compomer material (Dyractflow) using 2 single bottle bonding systems. METHOD AND MATERIALS: Sixty-four Class V cavity preparations were made on 32 sound, extracted human premolars, 1 preparation on the facial surface and 1 on the lingual surface. Teeth were then randomly divided into 2 groups. Group 1, which served as the control group, was restored as follows: group 1a, facial surface with PQ1 single-bottle bonding system plus TPH resin composite; group 1b, lingual surface with Prime & Bond NT single-bottle bonding system plus TPH. Group 2 was restored as follows: group 2a, facial surface with PQ1 plus Dyractflow compomer material; group 2b, lingual surface with Prime & Bond NT plus Dyractflow. After 24 hours of storage in water and subsequent thermocycling, each specimen was immersed in 0.2% basic fuchsin dye for 24 hours. The teeth were sectioned longitudinally and horizontally, and dye penetration at enamel and cementum margins was viewed at x30 magnification by 2 independently calibrated evaluators. Specimens were evaluated as either having leaked or not having leaked. RESULTS: No statistically significant differences in microleakage were noted between group 1 and group 2 specimens. CONCLUSION: Both single-bottle bonding systems, PQ1 and Prime & Bond NT, demonstrated equal effectiveness in reducing microleakage beneath compomer and composite restorations. PMID- 11203993 TI - John E. Echternacht: practitioner and community leader. AB - For Minnesota dentists with long memories, Dr Jack Echternacht is a legendary figure. He graduated from the University of Minnesota School of Dentistry in 1943. Except for a 3-year enlistment in the Navy during World War II, he has made his home and his professional life in Brainerd, on the edge of Minnesota's lake country. A few years after he started his general practice, reports began to appear about the striking reduction of dental caries in children's teeth when fluoride was placed in the drinking water. Excited by these prospects for better oral health, Dr Echternacht led a Chamber of Commerce initiative in 1954 to introduce fluoride into Brainerd's water supply. What seemed at first an easy victory turned into a 30-year struggle. Dr Echternacht's determination, persistence, and leadership during this fight for fluoridation led to his selection as a moral model in dentistry. PMID- 11203994 TI - Polymerization lights--light energy and wavelength. PMID- 11203995 TI - Rosacea. PMID- 11203996 TI - International implications of "oral health in America: a report of the Surgeon General". PMID- 11203998 TI - Restoring teeth that are endodontically treated through existing crowns. Part I: Survey of pulpal status on access. AB - OBJECTIVE: The purpose of this study was to identify the pulpal findings encountered by practitioners when accessing complete-coverage crowns that require nonsurgical root canal treatment and the relevance of coronal leakage to the success of the RTC. METHOD AND MATERIALS: The survey package consisted of a cover letter stating the instructions, rationale, and purpose for the questionnaire, a questionnaire with 8 short-answer questions, and a stamped, self-addressed envelope. A randomized sample of active dentists (300 general practitioners, 300 prosthodontists, and 300 endodontists) was selected. Collected data were analyzed with the chi-square test. RESULTS: A 60% response rate was obtained. Statistically significant differences were found among the practitioner groups, depending on the question. General practitioners and endodontists obtain access through crowns and maintain these crowns as final restoration significantly more often than do prosthodontists. Practitioners responded that teeth with complete crowns require nonsurgical root canal treatment after 5 to 10 years. CONCLUSION: Respondents believe that leakage must be addressed when endodontic access cavities in artificial crowns are restored after nonsurgical root canal treatment. General practitioners perform nonsurgical root canal treatment more frequently than do prosthodontists. Practitioners indicated that when teeth with complete crowns require nonsurgical root canal treatment, treatment is most often performed 5 to 10 years after placement of the crown. PMID- 11203997 TI - The Cerec 3--a quantum leap for computer-aided restorations: initial clinical results. AB - The Cerec 3 system simplifies and accelerates the fabrication of ceramic inlays, onlays, veneers, and quarter, half, and complete crowns for anterior and posterior teeth. Cerec 3 software simplifies occlusal and functional registration. Proper occlusion is established accurately and quickly; manual adjustment is reduced to a minimum. The separate grinding device, working true to morphologic detail and with fine surface quality, is connected to the optical unit by radio control. Equipped with a laser scanner, it can also be used for indirect application through a standard personal computer. The Cerec 3 system is network and multimedia ready and, in combination with an intraoral color videocamera or a digital radiography unit, can be used for patient education and for user training. The Cerec 3 system thus is a diagnostic, restorative, training, and documentation center for the dental practice. PMID- 11203999 TI - Restoring teeth that are endodontically treated through existing crowns. Part II: Survey of restorative materials commonly used. AB - OBJECTIVE: A survey was undertaken to categorize the materials used for the restoration of endodontic access openings through complete-coverage crowns after completion of nonsurgical root canal treatment. METHOD AND MATERIALS: The survey package consisted of a cover letter stating instructions, rationale, and purpose for the questionnaire, a questionnaire of 8 short-answer questions, and a stamped, self-addressed envelope. A randomized sample of active dentists (300 general practitioners, 300 prosthodontists, and 300 endodontists), was selected. Collected data were analyzed with the chi-square analysis. RESULTS: Most general practitioners (93%), endodontists (61%), and prosthodontists (75%) reported that they frequently or always permanently restore teeth after nonsurgical root canal treatment. Empress was the all-ceramic system used most commonly by prosthodontists (42%) and general practitioners (38%). A statistically significant difference in restorative material preference was found (P < 0.0001), depending on the type of crown used. CONCLUSION: Amalgam alone and in combination with bonding agents are materials of choice for restoration of access openings through all-metal complete crowns, while resin composite is the choice for all types of complete crowns involving porcelain. Endodontists preferred "other" materials. PMID- 11204000 TI - Wine, alcohol, and oral health, with special emphasis on dental erosion. AB - Wine is an essential component of the Mediterranean diet. Its consumption is increasing in many industrialized countries due to effective marketing. Wine may also have effects in the oral cavity mainly due to its acidity and alcohol content. This article briefly describes some effects of wine, both beneficial and detrimental, on oral and general health. In particular, the effect of wine on tooth enamel is demonstrated. PMID- 11204001 TI - Teaching of posterior resin-based composite restorations in Brazilian dental schools. AB - OBJECTIVE: The purpose of this study was to evaluate the teaching program of Class I and Class II resin-based composite (RBC) restorations in Brazilian dental schools and to observe if any differences were found from similar surveys conducted in North American, European, and Japanese dental schools. METHOD AND MATERIALS: A questionnaire containing 15 questions was distributed to 92 Brazilian dental schools, and 64 (70%) schools returned the questionnaire. The questions inquired the amount of time the curriculum dedicated to teaching of posterior RBC restorations, future expectation regarding the teaching time, limitation in extension of the occlusal width and the proximal box in Class II, contraindications for placing posterior RBC restorations, protocol for using bases and liners, brand of bonding agents and RBC used, instruments and techniques employed for finishing, cost relative to amalgam restorations, and biologic reactions related to the use of posterior RBC. The responses were calculated as percentages based on the number of schools that responded to the questionnaire. Where appropriate, the Chi-squared test and the Fisher exact test were used for statistical analysis. RESULTS: Of the dental schools that responded, 88% dedicated 10% to 50% of the teaching time in operative dentistry to posterior RBC restorations. A significant correlation (P = 0.041) was found between the percentage of time dedicated to the teaching of posterior RBC restorations and the higher cost of posterior RBC compared to amalgam restorations. Resin-based composite restorations cost 30% to 70% more than amalgam restorations in the 40% of dental schools that charged a fee. Posterior composites for large restorations in molars were used by 14% of the dental schools. Base and liner were not placed by 10% of dental schools in deep Class I or Class II RBC restorations. One school did not recommend acid etching of the dentin. CONCLUSION: No major differences were found in the teaching philosophy of posterior RBC restorations by comparing the Brazilian data to the data from similar surveys done in North America, Japan, and Europe. PMID- 11204002 TI - In vitro evaluation of the biocompatibility of dental alloys: fibronectin expression patterns and relationships to cellular proliferation rates. AB - OBJECTIVE: This short-term (72- to 96-hour) in vitro study on fibroblasts evaluated the biocompatibility of 3 single-phase dental alloys by determining cellular proliferation rates and the expression of a glycoprotein, fibronectin, which is involved in cellular adhesion processes. METHOD AND MATERIALS: Flow 2002 fibroblasts were cultured together with 3 single-phase dental alloys of different composition. Proliferation rates were determined by 5-bromodeoxyuridine incorporation. Fibronectin expression was determined by indirect immunofluorescence. RESULTS: At 72 hours, cells cultured with the alloy containing the lowest amount of noble elements (gold, platinum, and palladium) and the highest amount of silver exhibited significantly less proliferation than did controls. At 96 hours, only cultures with the alloy containing the greatest amount of noble elements behaved in a way similar to controls. Fibronectin organization in fibrils and in focal adhesions was correlated to higher cellular proliferation rates. CONCLUSION: Fibronectin organization could be a useful tool to determine the biocompatibility of dental alloys. Among the noble elements, palladium by itself exhibits very good biocompatibility. These indications could be useful for practitioners in the choice of the best alloy for specific clinical applications. PMID- 11204003 TI - Laboratory evaluation of a metal-priming agent for adhesive bonding. AB - OBJECTIVE: The purpose of this laboratory study was to determine the bond strength of a base metal alloy to a high-noble alloy and amalgam when a new chemical adhesion promoter was used in conjunction with a resin cement. METHOD AND MATERIALS: Specimens of high-noble alloy and amalgam were prepared in epoxy filled rings. Base metal cylinders were cast. The ends of the cylinders and the metal bonding substrates were wet ground and air abraded with aluminum oxide. The base metal cylinders were cemented with Panavia 21 resin cement after application of 1 of the following to the high-noble and amalgam metal surfaces: (1) Alloy Primer, (2) ED Primer, (3) Alloy Primer and ED Primer, or (4) tin plating. Bond values were determined after 24 hours' storage and after 3 months' storage and thermocycling. RESULTS: At both 24 hours and 3 months, tin plating yielded the highest bond strengths to a high-noble alloy, but the value for the Alloy Primer groups was not significantly lower. There was no statistically significant difference between the 24-hour and 3-month values within the 4 treatment regimens. CONCLUSION: Treatment of amalgam or high-noble alloy with either tin plating or Alloy Primer before bonding with Panavia 21 resin cement yielded equivalent bond strengths to a base metal alloy. ED Primer was not an effective metal primer. There was no advantage to combining Alloy Primer and ED Primer. PMID- 11204004 TI - Hugo A. Owens: dentist, civil rights leader, politician. AB - For 44 years Dr Hugo A. Owens was a distinguished practitioner and community leader in Portsmouth and Chesapeake, Virginia, and also served for a time as president of the National Dental Association. Besides his proclivity for dentistry, he was driven by two other passions: politics and civil rights. In 1970 he was one of the first African Americans ever elected to the Chesapeake City Council. He was reelected for the next term and appointed vice mayor, a position he held for 8 years. His political successes were preceded by his activities as a civil rights leader, which began in 1950 and lasted through the 1960s. In a remarkable series of negotiations and litigations, Dr Owens was the prime mover in the desegregation of the city of Portsmouth. In all three "careers," Dr Owens used dentistry as a home base for the expression of his activist philosophy of providing help for others when they were unable to help themselves. PMID- 11204005 TI - Improving dentist-patient relations. PMID- 11204006 TI - Fibrous dysplasia. PMID- 11204007 TI - [Coronary angioplasty compared with aortocoronary bypass in patients with multivascular coronary disease]. AB - Over the past two decades the use of angioplasty has rapidly expanded. As technology and experience have advanced, operators are increasingly faced with two-vessel and three-vessel disease. Coronary artery bypass graft surgery and coronary balloon angioplasty are two possible approaches for patients with multivessel coronary disease. Randomized trials comparing these two different procedures have found no difference in early as well as late mortality between assigned treatment groups. The Bypass Angioplasty Revascularization Investigation (BARI) showed a better long-term outcome with coronary artery bypass in the subgroup of patients with treated diabetes (35% died within 5 years after angioplasty compared with 19% who underwent surgery). Repeat revascularization was more common after angioplasty. Surgery offers more complete revascularization, but morbidity is higher; angioplasty is less invasive but patients are more likely to need another revascularization procedure mainly related to the occurrence of restenosis. Restenosis is often associated with the recurrence of symptoms requiring further revascularization. The use of stents and inhibitors of glycoprotein IIb/IIIa, minimally invasive surgical techniques and all-arterial grafting have the potential to change the scenery of coronary artery revascularization in the next few years. PMID- 11204008 TI - [Myocardial metabolism of calcium in heart failure: from physiology to new therapeutic perspectives]. AB - Development of heart failure is associated with an impairment of intracellular calcium handling. The precise mechanisms involved are still obscure. When membrane depolarization occurs, a small amount of extracellular calcium enters the intracellular milieu through the L-type channels. Such "trigger" calcium acts on specific receptors of the sarcoplasmic reticulum, that, in turn, according to the so-called calcium entry-calcium release mechanism, allows the release of a larger amount of calcium from the sarcoplasmic reticulum. Removal of calcium from the cytosol is the key event of the diastolic phase. Calcium removal from cytosol occurs through specific membrane pumps. Recent therapeutic approaches involving gene targeting of calcium pumps have yielded promising results. Specifically, increased levels of SERCA 2 in the myocardium have shown to enhance cardiac contractility under normal circumstances and in experimental heart failure. Future research is needed to confirm these findings in human heart failure. PMID- 11204009 TI - [Social costs of syncope]. AB - Syncope is a common syndrome that increases in prevalence with the aging of the population. The causes of this common symptom are multiple and the costs for the evaluation and treatment of syncope are enormous, especially with the use of highly technological approaches. Even when syncope is the expression of benign diseases, it may be the cause of significant morbidity for injuries, fractures and subsequent functional impairment, which particularly for elderly patients, matches that of other common chronic diseases. Finally, we cannot ignore the social costs caused by the reduction of working hours for diagnostic and therapeutic procedures and the subsequent loss of productivity. PMID- 11204010 TI - [Long-term clinical assessment of single-lead VDD electric stimulation]. AB - BACKGROUND: During the last decade single lead VDD pacing has been progressively affirmed as an electrotherapy of choice in patients with advanced atrioventricular block without alterations of the sinus function. It combines the benefits of P-synchronous ventricular pacing with an easy implant procedure when compared to the conventional DDD approach. The aim of this study was to evaluate the validity of such an approach in a large population of patients, all implanted in a single center. METHODS: From 1987 up to now, 317 patients, all affected by advanced atrioventricular block and without sinus node dysfunction, were implanted in our center with a single lead VDD pacemaker. During follow-up the persistence of a proper atrioventricular synchronization was assessed and evaluated. RESULTS: The mean follow-up was 3.9 +/- 2.7 years/patient (range 6-138 months). The 94.6% of implanted systems maintained the normal VDD pacing function. Permanent reprogramming in VVI mode was necessary in 17 patients (5.36%); in 12 (3.78%) because of chronic atrial fibrillation and in 5 (1.63%) for loss of atrial sensing. The percentage of atrial synchronization was optimal (> 98%) and acceptable (> 95%) in 81% and 19% of patients, respectively. Episodes of paroxysmal atrial fibrillation occurred in 3 patients. Neither inhibition by myopotentials nor occurrence of sinus node disease was observed during follow-up. These results are in accordance with those reported by previous studies, performed on a smaller population or on a multicenter basis, and are comparable with the results reported for conventional DDD pacemaker. CONCLUSIONS: Our results confirm the high reliability of the single lead VDD pacing system concerning the long-term persistence of a proper atrioventricular synchronization. Data showed above enforce our opinion that this pacing approach should be considered the treatment of choice in patients with advanced atrioventricular block and preserved sinus node function. PMID- 11204011 TI - [Bentall-DeBono intervention: 8 years of clinical experience]. AB - BACKGROUND: Annulo-aortic ectasia is a dilation of the aortic root with the involvement of the Valsalva sinuses. In 1968 Bentall and DeBono proposed to replace the aortic valve, the Valsalva sinuses and the ascending aorta with a composite tube graft containing aortic valve prosthesis. Consequently coronary ostia had to be reimplanted on the prosthetic tube. Recently the use of new materials has resulted in a more acceptable operative risk, and postoperative bleeding and late mortality have been reduced. METHODS: From January 1991 to December 1998, 44 out of 241 patients were operated on with the Bentall-DeBono procedure, affected by dissecting or expansive aneurysm of the ascending aorta. Of the 44 patients (35 males, 9 females, mean age 53.7 years), 3 presented with acute aortic dissection, 5 were asymptomatic, 10 were in NYHA functional class II, 14 in class III, 9 in class IV, and 2 in CCS class 4; 1 patient had dysphonia; 37 patients presented with isolated aortic regurgitation, and 7 associated aortic valvular stenosis. The diagnosis of acute dissection was made by transesophageal echocardiography and that of expansive aneurysm by thorax helical computed tomographic scanning and/or magnetic resonance imaging and cardiac catheterization. Follow-up was obtained in 100% of the patients for an average of 23 +/- 20.9 months (range 4-79 months). RESULTS: Four patients (9%) died; in 4 patients (9%) postoperative bleeding needed reoperation, in 5 (11.4%) a permanent pacemaker for atrioventricular block was implanted, and 1 patient (2.3%) had transient hemiparesis. At univariate analysis predictive factors for operative risk were NYHA functional class IV (p < 0.005) and atherosclerotic etiology (p < 0.05). At follow-up 7 late deaths occurred for an actuarial survival at 24 months of 75 +/- 9%. Causes were sudden death in 3 patients, cardiac failure in 3 and stroke in 1 patient; 31 surviving patients (94%) were in NYHA functional class I and 2 patients in class II (6%). CONCLUSIONS: The Bentall DeBono procedure involves moderate risk with good results; clinical presentation and associated valvular pathology influence early and mid-term results. PMID- 11204012 TI - [Detection and assessment of myocardial stunning with perfusion tomographic scintigraphy using gated SPECT]. AB - BACKGROUND: Gated-SPECT using 99mTc-labeled flow tracers provides the simultaneous assessment of global and regional myocardial perfusion and function. The aim of this study was to identify patients with stress-induced postischemic stunning, among those with reversible stress perfusion defects, and patients with artifactual defects among those with fixed defects, in order to assess the value of the functional data provided by gated acquisition of perfusion imaging in the characterization of ischemia. METHODS: We studied 221 consecutive patients who underwent conventional diagnostic dual day stress/rest gated-SPECT following injection of 925 MBq of 99mTc-tetrofosmin using a dual head SPECT camera, 115 of whom (52%) showed reversible perfusion defects, and 66 (30%) fixed defects. Perfusion was analyzed on ungated images using 20 segments scored on a 5-point scale (0 = normal, 4 = no uptake), while wall thickening was assessed visually on stress/rest end-systolic images using a 4-point score (0 = normal, 3 = absence of wall thickening). Left ventricular ejection fraction and volumes were calculated using an automatic algorithm (quantitative gated-SPECT). Fifty-two out of 221 (23.5%) patients underwent coronary angiography. RESULTS: In 40/115 (35%) patients with reversible perfusion defects, post-stress left ventricular ejection fraction was > 5% lower than that at rest (Group A: stunned), whereas in the remaining 75 patients, post-stress left ventricular ejection fraction was either +/- 5% or greater than that at rest (Group B: non-stunned). Peak exercise angina and ischemic electrocardiographic response to exercise were present in 79 and 58% respectively of Group A patients and in 33 and 39% of Group B patients. The number of patients with multivessel disease was significantly higher in Group A compared to Group B (58 vs 41%, p < 0.05). The total stress and rest perfusion scores were significantly higher in Group A than in Group B (p < 0.01); even the total stress wall thickening score was significantly higher in Group A (p < 0.001). As for global parameters, post-stress end-systolic volume was significantly higher in the stunned group (p < 0.05). In 40 out of 66 (60.5%) patients without reversible ischemia fixed defects were judged to be ischemic (Group C), while in 26/66 (39.5%) they were attributed to attenuation artifacts (Group D). Eighty percent of Group C patients had a previous myocardial infarction against none of Group D. Stress/rest perfusion and wall thickening scores were significantly higher in Group C than in Group D. CONCLUSIONS: Gated SPECT myocardial perfusion evaluation allowed us to identify a subgroup of post stress stunned coronary artery diseased patients. The post-stress left ventricular ejection fraction reduction in this population seems to be due to the increase in end-systolic volume. The stunned patients showed more severe perfusion defects and wall thickening abnormalities. PMID- 11204013 TI - [Left atrial myxoma. Clinical and surgical features in 26 surgically treated cases]. AB - BACKGROUND: Left atrial myxomas are the most common benign intracardiac tumors. The aim of this study was to compare our experience with the data reported in the literature. METHODS: Between May 1985 and August 1999, 26 patients (8 males, 18 females) with left atrial myxomas underwent surgical resection of these tumors at the Department of Cardiac Surgery, Ospedali Riuniti of Bergamo (Italy). Symptoms included congestive heart failure, dyspnea, arrhythmias, chest pain and syncope. Diagnosis was established preoperatively in all patients by echocardiography and angiocardiography was performed in 8 cases. All tumors were excised with a wide margin of uninvolved atrial septum. Two patients underwent concomitant coronary artery bypass. RESULTS: There was 1 early death due to irreversible ventricular fibrillation. Follow-up was completed for the 25 late survivals. Three patients died, years after operation, due to extracardiac causes. One patients had recurrence of the tumor, which was successfully removed 4 years after initial operation. All other patients are asymptomatic and free from disease. CONCLUSIONS: Operation for left atrial myxoma can be undertaken solely on the basis of echocardiographic findings, but coronary angiography should be performed in older patients who are at risk for coronary artery disease. Surgical excision of left atrial myxomas must be performed as soon as possible after diagnosis is established because of the high risk of valvular obstruction or systemic embolization. Biatrial approach allows for the inspection of the four cardiac chambers, limits manipulation of the mass, and facilitates the complete excision of the tumor. Thus, surgical intervention can be curative for patients with left atrial myxomas and most of these can expect an excellent outcome. Since late recurrence, although rare, has been reported, especially in familial myxomas, long-term clinical and echocardiographic follow-up is recommended. PMID- 11204014 TI - [Efficacy of treatment with rt-PA of massive pulmonary embolism in patients with contraindications for thrombolytic therapy]. AB - Pulmonary embolism is a life-threatening condition that is accompanied by significant morbidity and mortality. In massive pulmonary embolism, where restoration of pulmonary arterial flow is urgently required, the only options available are surgical thromboembolectomy and/or thrombolytic therapy. Unfortunately, a large part of thromboembolic diseases is also considered as an absolute or relative contraindication to thrombolysis. The purpose of this paper was to emphasize the possibility of new thrombolytic agents of disregarding, according to circumstances, the contraindications to thrombolytic treatment. PMID- 11204015 TI - [Right pleural effusion in aortic dissecting aneurysm]. AB - Right hemorrhagic pleural effusion may be a presenting sign of thoracic aortic dissecting aneurysm. We describe 2 cases of massive right hemorrhagic pleural effusion and dissection of the descending aorta (type B) detected at tomographic scan. Transesophageal echocardiography ruled out a retrograde dissection of the ascending aorta. Right hemorrhagic pleural effusion is an unusual clinical presentation in thoracic aorta dissection and, up to now, the underling pathophysiology of this sign has not been defined yet. PMID- 11204016 TI - [Guidelines on the appropriate use of non-invasive diagnostic techniques]. PMID- 11204017 TI - [Comparative study of the effect of ACE-inhibition, angiotensin II antagonism, and calcium channel blockade on flow-mediated vasodilation in patients with coronary disease (BANFF study]. PMID- 11204018 TI - [Association of serology with the endovascular presence of Chlamydia pneumoniae and cytomegalovirus in coronary artery and vein graft disease]. PMID- 11204019 TI - [Infections, inflammation, and the risk of coronary heart disease]. PMID- 11204020 TI - [Estimation of contribution of changes in coronary care to improving survival, event rates, and coronary heart disease mortality across the WHO MONICA Project populations]. PMID- 11204021 TI - [Prevention of rejection in cardiac transplantation by blockade of the interleukin-2 receptor with a monoclonal antibody]. PMID- 11204022 TI - [Efficacy of implantable cardioverter-defibrillators for the prevention of sudden death in patients with hypertrophic cardiomyopathy]. PMID- 11204023 TI - [Guidelines: diverse value of Manzoni's "proclamations"?]. PMID- 11204024 TI - Molecular structure and function of erythrocyte blood group antigens. PMID- 11204025 TI - Complications of autologous hematopoietic stem cell transplantation. AB - Myeloablative therapy followed by autologous hematopoietic stem cell (HSC) transplantation is a therapeutic option proposed for a variety of hematological and non-hematological diseases. However, although mortality due to this procedure is steadily decreasing, patients are still exposed to the risk of a number of complications negatively affecting their expectancy or quality of life. Adverse events due to HSC harvesting are rare and generally reversible. The early post transplant complications include infections, mucositis, hepatic veno-occlusive disease and various acute organ toxicities. Immune derangement is a leading cause of most late events, such as viral or fungal infections, auto-immune manifestations and secondary neoplasms, of which secondary AML/MDS are the most commonly reported. In line with the favoured pathogenetic explanation, neoplastic clones previously established during conventional treatment are harvested and reinfused at the time of autografting. Other late effects are single organ dysfunction due to the underlying disease and treatment toxicities combined with infectious and post-infectious phenomena. The lungs, heart, CNS and reproductive system are the most investigated targets, but no clinical patterns have been identified as specific for autografting. PMID- 11204026 TI - Hodgkin's disease in the elderly: a single institution retrospective study of 40 patients aged 65 or over. AB - Out of 485 patients with Hodgkin's disease (HD) treated in our institution between 1970-1998, 40 (8.2%) patients aged 65 or over at the date of the first presentation were examined retrospectively. The localization of the disease was more frequently infradiaphragmatic and rarely mediastinal in the elderly. The time that elapsed from the first clinical sign to the diagnosis of HD was twice as long as that in the young patient population. Since the first treatment was often inadequate and due to severe associated diseases, therapeutic and overall survival results in this patient population were less favourable than in the case of young patients. However, the relapse-free survival rate of the elderly patients treated successfully did not differ from that of the young patient population. Complete healing should be the final aim of treatment in the aged population, while the status of the patient, associated diseases and life expectancy not related with HD should also be taken into consideration. Besides the search for effective and less toxic treatment strategies and supportive therapy, more frequent and overall patient follow-up and care is of great importance. PMID- 11204027 TI - Lymphokine-activated killer (LAK) cells and cytokines synergize to kill clonal cells in acute myeloid leukemia (AML) in vitro. AB - We studied the influence of autologous lymphokine-activated-killer (LAK) cells on the survival of clonal and CD34-positive bone marrow (BM) cells from patients with acute myeloid leukemia (AML) in a coculture assay in vitro. (1) LAK cells were grown in the presence of IL-2, in some cases additionally with IL-6. (2) These cytotoxic cells were cocultured with (untreated or cytokine pretreated) AML BM cells obtained at different stages of the disease. Therefore BM cells were (a) either frozen in liquid nitrogen or (b) precultured for 14 days with cytokines: IL-1beta, IL-3, IL-6, erythropoietin (EPO), stem cell factor (SCF) with ('Cytok1') or without granulocyte macrophage colony stimulating factor (GM-CSF) ('Cytok2') or with no added cytokines ('ISC/FCS') as a control. (3) Southern blot analysis was used to detect clonal BM cells. At diagnosis, 76 of 151 cases (50%) studied showed clonal gene rearrangements in marker genes. (4) Southern blot analysis and flow cytometry were used to compare the amount of clonal and CD34 positive BM cells before and after coculture procedures. Coculture experiments with untreated BM and autologous LAK cells led to a reduction of clonal cells in 2 of 5 cases at diagnosis, in 11 of 17 BM samples in complete remission but not in the one case studied at relapse. Similar results were found if precultured AML cells (with or without cytokines) were cocultivated with LAK cells. However the cytotoxic effect of LAK cells was more pronounced if cytokines (especially GM-CSF and SCF) were comprised. Our data indicate, that (1) clonality in AML can be demonstrated by Southern blot analysis; (2) CD34 positive cells in AML are clonal, gene rearranged cells; (3) clonal cell populations persist in BM during complete remission and relapse in most of the patients; (4) incubation of AML-BM cells with LAK cells lead to a reduction of clonal, rearranged cells in 11 of 17 AML cases in complete remission, but only in 2 of 6 cases at diagnosis or relapse; (5) AML cells can be sensitized to theLAK cell treatment by preincubation of AML-BM cells with cytokines (IL-1beta, IL-3, IL-6, SCF, EPO and GM-CSF) or by adding SCF to the coculture conditions. Southern blot analysis and flow cytometry are appropriate methods to detect and quantify leukemic disease. Cytokines and LAK cells synergize to kill AML blasts in vitro. This is a feasible approach to immunotherapy of AML and merits further investigations. PMID- 11204028 TI - Effects of a membrane-metallopeptidase blocking agent thiorphan in long-term cultures of human bone marrow. AB - Thiorphan [(DL-3-mercapto-2-benzylpropanoyl)-glycine], a drug blocking the activity of membrane metalloendopeptidase EC 3.4.24.11 (CD10, CALLA), was added to long-term cultures of human bone marrow. Progression of the cultures was assessed by cell counts, cytology and clonogenic (GM-CFU) ability of the non adherent cells in the supernatant and by morphology of the adherent stromal layer. A stimulatory effect on hematopoiesis was noted. PMID- 11204029 TI - Catastrophic antiphospholipid syndrome in cancer. AB - Antiphospholipid syndrome is characterized by the presence of antiphospholipid antibodies resulting in arterial and venous thromboembolism. Apart from primary cases, this syndrome is often associated with autoimmune diseases. Around 50 cases of catastrophic antiphospholipid antibody syndrome have been reported as yet. Authors describe the first case of catastrophic antiphospholipid syndrome associated with gastric cancer. Apart from presenting the clinical case, authors also discuss the possible pathomechanism of this associated disorder including the role of immunological factors, as well as antiphospholipid antibodies. PMID- 11204030 TI - Leg ulcer in hydroxyurea-treated patients. AB - A cutaneous ulcer is a lesser known complication of hydroxyurea treatment. Out of 39 patients [18 polycythaemia vera (PV), 13 essential thrombocythaemia (ET), 4 chronic myeloid leukemia (CML), 4 undefined myeloproliferative diseases (MPD)] treated with hydroxyurea, 6 (4ET, 1PV, 1CML) developed a cutaneous ulcer during a period of less that 2 years' treatment. In all but one of the patients the ulcers were situated in the ankle region. At the time of onset of ulceration, none of them had extreme values in their peripheral blood counts. All had one or more of the predisposing factors such as minor trauma or mild varicosity. None of the patients had any alteration in arterial or venous circulation when examined by non-invasive means. No hyperviscosity was found as measured by capillary viscosimeter. The ulcers were cured in three patients without discontinuation of the drug. One patient later developed an ulcer on the other leg. The ulcers healed in two patients only after having stopped the hydroxyurea medication. One patient still had the ulcer when she succumbed to the underlying CML in transformation. In conclusion, cutaneous, ulceration of the leg is relatively common during hydroxyurea therapy. Predisposing factors are also involved in its development. Its healing does not necessarily require the discontinuation of the drug. PMID- 11204031 TI - Iron stores in multi-transfused thalassaemic patients seem not to be influenced by the HLA system. AB - The HLA-A and -B antigens of 99 Greek patients with transfusion dependent homozygous beta thalassaemia were determined. The HLA antigen distribution in thalassaemic patients with a severe transfusion siderosis and in patients without signs of siderosis were compared to that of 400 healthy unrelated controls from the same population. There is an increase of HLA-B 14 antigen in both groups of thalassaemics as compared with the controls. No significant difference exists in the distribution of all the other HLA antigens between the two sub-groups of thalassaemics or with the controls. PMID- 11204032 TI - Osteolytic lesions as a presenting sign of acute myeloid leukemia. AB - Osteolytic lesions rarely occur in acute myeloid leukemia (AML). We reported an atypical form of the disease, with marrow fibrosis and osteolytic lesions, in a 17-year-old patient, whose main symptom was lumbar pain. Diagnosis of AML was established by bone marrow and lymph node histological analysis. Computed tomography (CT) scan and 99mTc-MDP bone scintyscan revealed osteolytic lesions. After remission-induction, bone marrow aspirate and biopsy showed no evidence of leukemic infiltration, nevertheless bone abnormalities persisted on 99mTc-MDP bone scintyscan, suggesting residual disease. Suspect bone areas were irradiated with symptomatic improvement and 99mTc-MDP bone scintyscan showed the appearance of more condensed bone compared with the pre-radiotherapy pattern. Twelve months later he was readmitted to the hospital due to relapse of AML and died of sepsis within a few weeks. This report illustrates the usefulness of histological studies to establish diagnosis of AML in atypical cases, as well as the importance of CT scan and bone scintigraphy scan for the identification of osteolytic lesions. It also provides additional data as evidence that although osteolytic lesions indicate an adverse prognosis in AML, local irradiation results symptomatic relief. PMID- 11204033 TI - A commentary: the impact of the IEEE TRANSACTIONS ON REHABILITATION ENGINEERING on the field of rehabilitation engineering and science. AB - The IEEE TRANSACTIONS ON REHABILITATION ENGINEERING, founded 8.5 years ago, has survived, thrived, been of high quality, attracted the best authors in its field and related fields, been the publication of choice for manuscript submission in the rehabilitation engineering and related science area, possessed a wide and international distribution and loyal readership, been oft-cited, been financially sound, and made a marked impact on the field of Rehabilitation Engineering. PMID- 11204034 TI - Optimal spatial filtering of single trial EEG during imagined hand movement. AB - The development of an electroencephalograph (EEG)-based brain-computer interface (BCI) requires rapid and reliable discrimination of EEG patterns, e.g., associated with imaginary movement. One-sided hand movement imagination results in EEG changes located at contra- and ipsilateral central areas. We demonstrate that spatial filters for multichannel EEG effectively extract discriminatory information from two populations of single-trial EEG, recorded during left- and right-hand movement imagery. The best classification results for three subjects are 90.8%, 92.7%, and 99.7%. The spatial filters are estimated from a set of data by the method of common spatial patterns and reflect the specific activation of cortical areas. The method performs a weighting of the electrodes according to their importance for the classification task. The high recognition rates and computational simplicity make it a promising method for an EEG-based brain computer interface. PMID- 11204035 TI - Real-time EEG analysis with subject-specific spatial patterns for a brain computer interface (BCI). AB - Electroencephalogram (EEG) recordings during right and left motor imagery allow one to establish a new communication channel for, e.g., patients with amyotrophic lateral sclerosis. Such an EEG-based brain-computer interface (BCI) can be used to develop a simple binary response for the control of a device. Three subjects participated in a series of on-line sessions to test if it is possible to use common spatial patterns to analyze EEG in real time in order to give feedback to the subjects. Furthermore, the classification accuracy that can be achieved after only three days of training was investigated. The patterns are estimated from a set of multichannel EEG data by the method of common spatial patterns and reflect the specific activation of cortical areas. By construction, common spatial patterns weight each electrode according to its importance to the discrimination task and suppress noise in individual channels by using correlations between neighboring electrodes. Experiments with three subjects resulted in an error rate of 2, 6 and 14% during on-line discrimination of left- and right-hand motor imagery after three days of training and make common spatial patterns a promising method for an EEG-based brain-computer interface. PMID- 11204036 TI - Using time-dependent neural networks for EEG classification. AB - This paper compares two different topologies of neural networks. They are used to classify single trial electroencephalograph (EEG) data from a brain-computer interface (BCI). A short introduction to time series classification is given, and the used classifiers are described. Standard multilayer perceptrons (MLPs) are used as a standard method for classification. They are compared to finite impulse response (FIR) MLPs, which use FIR filters instead of static weights to allow temporal processing inside the classifier. A theoretical comparison of the two architectures is presented. The results of a BCI experiment with three different subjects are given and discussed. These results demonstrate the higher performance of the FIR MLP compared with the standard MLP. PMID- 11204037 TI - Implantable selective stimulator to improve bladder voiding: design and chronic experiments in dogs. AB - Among the treatments to enhance the bladder voiding, the sacral roots neurostimulation is one of the most promising techniques. The electrostimulation of sacral nerves provokes a simultaneous contraction of the detrusor muscle as well as the external urethral sphincter (EUS). A new simplified-architecture implantable stimulator with its wireless controller have been designed to investigate high-frequency inhibition stimulation strategies. This innovative technique based on high-frequency inhibition reduces sphincter activity during stimulation. Low-frequency current pulses also applied to the sacral roots induces contraction of the detrusor muscle resulting in low pressure voiding. Chronic experiments were carried out on ten male mongrel paraplegic dogs. One cuff electrode was implanted along with each stimulator for eight months. The animals were stimulated twice a day using the prototypes of our implantable selective stimulator while voided and residual urine volume were measured during the procedure. These experiments revealed that the proposed stimulation strategy enhances bladder voiding by more than 50% in comparison with low-frequency only stimulation. The residual urine volume was reduced to an average of 9% and low pressure micturition was achieved as shown by weekly cystourethrogram. PMID- 11204038 TI - EMG-based prediction of shoulder and elbow kinematics in able-bodied and spinal cord injured individuals. AB - We have evaluated the ability of a time-delayed artificial neural network (TDANN) to predict shoulder and elbow motions using only electromyographic (EMG) signals recorded from six shoulder and elbow muscles as inputs, both in able-bodied subjects and in subjects with tetraplegia arising from C5 spinal cord injury. For able-bodied subjects, all four joint angles (elbow flexion-extension and shoulder horizontal flexion-extension, elevation-depression, and internal-external rotation) were predicted with average root-mean-square (rms) errors of less than 20 degrees during movements of widely different complexities performed at different speeds and with different hand loads. The corresponding angular velocities and angular accelerations were predicted with even lower relative errors. For individuals with C5 tetraplegia, the absolute rms errors of the joint angles, velocities, and accelerations were actually smaller than for able-bodied subjects, but the relative errors were similar when the smaller movement ranges of the C5 subjects were taken into account. These results indicate that the EMG signals from shoulder and elbow muscles contain a significant amount of information about arm moVement kinematics that could be exploited to develop advanced control systems for augmenting or restoring shoulder and elbow movements to individuals with tetraplegia using functional neuromuscular stimulation of paralyzed muscles. PMID- 11204039 TI - Determination of generic body-seat interface shapes by cluster analysis. AB - The purpose of this study was to determine typical or generic shape patterns of the buttock-seat interface for elderly wheelchair users. The group of subjects was composed of 30 elderly people (aged 65 or older) and the shapes of the body seat interface were measured by the electronic shape sensor (ESS). By analyzing the dissimilarity in geometrical shape descriptors or parameters, four distinct generic shapes were identified by means of the cluster analysis method. The results suggest that the generic shapes were mainly characterized by the lateral symmetry of the shapes. The determination of elderly people's seat interface shapes into distinct clusters may lead to a more comprehensive understanding of the seat support interface and more effective seat cushion designs. PMID- 11204040 TI - A navigation system for increasing the autonomy and the security of powered wheelchairs. AB - Assistive technology is an emerging area where some robotic devices can be used to strengthen the residual abilities of individuals with motor disabilities or to substitute their missing function thus helping them to gain a level of independence at least in the activities of daily living. This paper presents the design of a navigation system and its integration with a commercial powered wheelchair. The navigation system provides the commercial wheelchair with a set of functions which increase the autonomy of elderly and people with motor disabilities. In general, a robot device must be adapted to assistive applications in such a way as to be easily managed by the user. Users, especially young ones, prefer to directly control the robotic device and this aspect of usability has to be managed without affecting the security and efficiency of the navigation module. These aspects have been considered as specifications for the navigation module of powered wheelchairs. Different autonomy levels of the navigation module and proper user interfaces have been developed. Two autonomy levels have been designed. Simple collision avoidance is also implemented in order to stop the mobile base when an obstacle is detected. The preliminary technical tests performed on the navigation system have shown satisfactory results in terms of security and response time. A modular solution for the navigation module was considered in order to simplify the adaptation of the module to different powered wheelchairs. PMID- 11204041 TI - Electrotactile adaptation on the abdomen: preliminary results. AB - Electrotactile (electrocutaneous) stimulation at currents greater than sensation threshold causes sensory adaptation, which temporarily raises the sensation threshold and reduces the perceived magnitude of stimulation. After 15 min of moderately intense exposure to a conditioning stimulus (10 s on, 10 s off), the sensation threshold elevation for seven observers was 60-270%, depending on the current, frequency, and number of pulses in the burst structure of the conditioning stimulus. Increases in any of these parameters increased the sensation threshold elevation. Adaptation and recovery were each complete in approximately 15 min. PMID- 11204042 TI - WARD: a pneumatic system for body weight relief in gait rehabilitation. AB - The paper presents Walking Assistance and Rehabilitation Device (WARD), a system for walking rehabilitation devised to relieve the patient of his/her body weight of a constant and prescribed amount by externally supporting the subject at the upper trunk and pelvis level by means of a harness. The system is based on a pneumatic actuator that has proved to be effective at maintaining a constant relief force. The constancy of this force that should be maintained even under high body weight support (BWS) conditions (70-80% of body weight) seems to be important for a correct motor pattern. A law has been identified that may be useful to adjust walking speed as a function of the prescribed BWS. WARD is simple to construct, practical to use, and has been characterized on healthy subjects. PMID- 11204043 TI - The use of selective electrical stimulation of the quadriceps to improve standing function in paraplegia. AB - Persons with spinal cord injury (SCI) can benefit significantly from functional neuromuscular stimulation (FNS) systems for standing if manual tasks can be performed while upright. Using FNS to sufficiently activate the knee extensors to rise from a sitting position often results in inadvertent activation of the rectus femoris and/or sartorius, which flex the hip. In this study, intramuscular electrodes implanted in the vastus lateralis and medialis of four subjects with SCI were used to activate these muscles individually and simultaneously to measure knee extension moment. Support forces applied to the arms and feet were measured while upright to quantify the effects of recruiting rectus femoris and/or sartorius. In three of the four subjects, vastus lateralis, by itself, generated adequate knee extension moment for rising from a chair and to maintain static standing. Simultaneous activation of the vastus lateralis and medialis using a bifurcated electrode generated adequate knee extension moment in one subject, and was within 10% of the required moment in another. While upright, activation of the rectus femoris resulted in arm support force increases of 4-11% body weight, while deactivation resulted in arm support force decreases of 6-9% body weight. The results indicate that selective activation of the vastus lateralis, individually or in combination with vastus medialis, can improve current FNS standing systems by reducing the arm support forces required to remain upright. PMID- 11204044 TI - Patient-driven control of FES-supported standing up and sitting down: experimental results. AB - A patient-driven control strategy for standing-up and sitting-down was experimentally tested on two paraplegic patients by applying functional electrical stimulation (FES) to the quadriceps muscle. The strategy--also known as "patient-driven motion reinforcement" (PDMR)--was developed by computer simulations reported in a former study. It is based on an inverse dynamic model (IDM) that predicts the stimulation pattern required to maintain the movement as it is initiated by the patient's voluntary effort. For reasons of safety and weight relief, the movement was supported by a seesaw construction. After some practice the patients were able to influence the stimulator output and to control the movement by their voluntary effort. Consequently, no pre-programmed reference trajectory was required. As a positive side effect, upper body effort could be minimized compared to trials without FES. To achieve a satisfactory performance of the PDMR controller a careful parameter identification of the inverse dynamic model was fundamental. PMID- 11204045 TI - Pain: a bridge linking anesthesiology and sleep research. PMID- 11204046 TI - Beta/Gamma EEG activity in patients with primary and secondary insomnia and good sleeper controls. AB - STUDY OBJECTIVE: Several studies have shown that patients with insomnia exhibit elevated levels of Beta EEG activity (14-35 Hz) at or around sleep onset and during NREM sleep. In this study, we evaluated 1) the extent to which high frequency EEG activity is limited to the 14-32 Hz domain, 2) whether high frequency EEG activity (HFA) is associated with discrepancies between subjective and PSG measures of sleep continuity, and 3) the extent to which high frequency EEG activity occurs in patients with primary, as opposed to secondary, insomnia. DESIGN: Three groups (n=9 per group) were compared: Primary Insomnia, Insomnia secondary to Major Depression, and Good Sleeper Controls. Groups were matched for age, sex and body mass. Average spectral profiles were created for each NREM cycle after removing waking and movement epochs and epochs containing micro- or mini-arousals. SETTING: Sleep Research Laboratory PATIENTS OR PARTICIPANTS: Patients with primary and secondary insomnia INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Subjects with Primary Insomnia exhibited more average NREM activity for Beta-1 (14-20Hz), Beta-2 (20-35Hz) and Gamma activity (35-45Hz) than the other two groups (p.<.01). Group differences were also suggestive for Omega activity (45.0-125Hz) (p.<.10), with MDD subjects tending to exhibit more activity than the other groups. Correlational analyses revealed that average NREM Beta-1 and Beta-2 activity tended to be negatively correlated with subjective-objective discrepancy measures for total sleep time and sleep latency. CONCLUSIONS: Our results confirm that Beta activity is increased in Primary Insomnia. In addition, our data suggest that high frequency activity in patients with Primary Insomnia is limited to the Beta/Gamma range (14-45 Hz), and is negatively associated with the perception of sleep. PMID- 11204047 TI - Paradoxical sleep is characterized by uncoupled gamma activity between frontal and perceptual cortical regions. AB - STUDY OBJECTIVES: Coherent activity of fast activity has been postulated to be a common language of the brain involved in the processing of information and in integration of spatially separated but temporally correlated stimuli into whole events. Any disruption affecting temporality would result in distortion of cognitive activity. Dreaming during paradoxical sleep (PS) shows cognitive alterations that mimic frontal lobe dysfunction. Decreased temporal coupling of EEG between frontal and perceptual regions was hypothesized. The main objective was to explore temporal relationships of fast activity among these regions. DESIGN: N/A. SETTING: N/A. PARTICIPANTS: 8 young adults. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Interhemispheric (INTERr) and intrahemispheric (INTRAr) EEG correlation spectra (1-50 Hz) were obtained for wakefulness, stage 2, stage 4, and PS during the second night spent at the laboratory. INTERr showed a significant overall increase during sleep in comparison to wakefulness, whereas INTRAr of fast activity (27-48 Hz) between frontal-perceptual regions (F-P, F-O, F-T, Fp-P, Fp-T) decreased exclusively during PS while INTRAr among perceptual regions (P-O, P-T, O-T) maintained wakefulness values. CONCLUSIONS: Present results demonstrate state- and frequency-dependent shifts on temporal coupling. The hypothesized decrease in correlation of fast activity between frontal and perceptual regions during PS was confirmed. This decrease of temporal coupling might underlie the loss of voluntary direction of thinking and congruence with social and temporal context and the lack of judgment and passive acceptance of bizarreness during PS dreaming. The wakefulness levels in correlation of fast activity among perceptual regions might explain perceptual acuity during PS dreaming. PMID- 11204048 TI - Effects of sleep on spinal nociceptive reflexes in humans. AB - Controversy continues to surround the monosynaptic and polysynaptic spinal reflexes during the different stages of sleep. In animal studies both of these reflexes were found to be depressed during desynchronized sleep. In humans, the H reflex was unchanged whereas the second component of the nociceptive flexion reflex was increased. However, abolition of the H reflex and F waves during REM sleep has also been reported. The aim of this investigation was to examine the effects of different sleep stages on the polysynaptic nociceptive flexion reflex. Six healthy volunteers were studied. The RIII reflex was studied according to Willer's method (1977) during the different stages of NREM and REM sleep. The RIII reflex threshold was found to increase during stage 2 of NREM sleep. It remained higher during stages 3 and 4. During REM sleep a further increase in the reflex threshold was observed. The reflex latency was prolonged during stage 4 of NREM sleep. There was evidence of further latency prolongation during REM sleep. It was also during REM sleep that the maximum increase in the amplitude and duration of the reflex were recorded. PMID- 11204049 TI - Spontaneous spike activity of spinoreticular tract neurons during sleep and wakefulness. AB - Sleep mentation studies infer that pain sensation in humans may be reduced during active REM sleep. However, to provide a mechanistic explanation for this phenomenon, few, if any neurophysiological studies have been performed at the lumbar level from neurons comprising classical pain pathways during sleep and wakefulness. The spinoreticular tract is one such classical pathway that has been implicated in the rostral transmission of nociceptive information. The present study was performed to determine if the activity of spinoreticular tract (SRT) neurons is dependent upon behavioral state. Accordingly, extracellular recording techniques were used to monitor the activity of identified SRT neurons in unanesthetized chronic cats during sleep and wakefulness. The ongoing spike activity of SRT neurons was found to be relatively uniform when the states of quiet wakefulness and quiet sleep were compared. However, during active sleep, the majority of the SRT neurons sampled underwent a sustained reduction in spike activity. Marked facilitation of SRT cell activity occurred in a few instances. These data provide the first unitary evidence supporting earlier evoked potential, psychophysical and clinical studies that ascending sensory information in a classical pain pathway is regulated in a state-dependent fashion. PMID- 11204050 TI - Propofol action in both spinal cord and brain blunts electroencephalographic responses to noxious stimulation in goats. AB - STUDY OBJECTIVES: Anesthetics, including propofol, depress the electroencephalogram (EEG) and neuronal activity in the midbrain reticular formation (MRF). Because propofol has anesthetic effects in the spinal cord, we hypothesized that it would indirectly depress EEG and MRF neuronal responses to noxious stimulation in part by a spinal cord action. DESIGN: Six goats were anesthetized with isoflurane and the jugular veins and carotid arteries were isolated to permit cranial bypass and differential propofol delivery. A noxious mechanical stimulus was applied to the distal forelimb while recording bifrontal EEG and MRF single-unit activities. Propofol was separately administered to the cranial (0.08 +/- 0.06 mg/kg) and torso circulations (4 mg/kg) and the noxious stimulus applied at 1,5, 10, and 15 min after each injection. SETTING: N/A. PATIENTS OR PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Noxious stimulation decreased total power (TP) from 96 +/- 33, microV2/Hz to 38 +/- 20microV2/Hz, (mean +/- SD) and increased spectral edge frequency (SEF) from 10 +/- 3 Hz to 19 +/- 5 Hz (p<0.01). Propofol administered to the torso prevented stimulus-evoked changes in TP (121+/- 80 microV2/Hz, 121 +/- 74 microV2/Hz, 114 +/- 74 microV2/Hz at 1,5, and 10 min respectively, p<0.01 compared to control evoked response) and SEF (11 +/- 6Hz, 9 +/- 2Hz, 10 +/- 6Hz, and 12 +/- 5Hz at 1, 5, 10 and 15 min, respectively, p<0.001 compared to control evoked response). Propofol administered to the cranial circulation significantly blunted the EEG and MRF response, while torso-administered propofol had slight effects on MRF responses. CONCLUSIONS: Propofol blunted the EEG response to noxious stimulation in part via a subcortical action. PMID- 11204051 TI - Nociceptive responsiveness during slow-wave sleep and waking in the rat. AB - Brainstem neurons that are thought to modulate pain are reported to have state dependent discharge rates. Yet, the effect of behavioral state upon nociceptive transmission has not been well studied. Therefore, we examined responses to noxious thermal stimulation of the rat hindpaw presented during different behavioral states. Noxious thermal stimuli were applied to rats as they spontaneously cycled through waking and sleeping states. Two different methods of heating the paw - a focused light bulb ("radiant heat") and a CO2 laser ("laser heat")-were employed. Regardless of the heating method used, rats withdrew from noxious thermal stimulation when it was applied in each behavioral state tested. When rats were tested with radiant heat, the withdrawal latency from noxious heat was shorter during slow-wave sleep than during waking. In contrast, when tested with laser heat, there was no difference in either the response latency or magnitude evoked by noxious heat across sleep/wake states. Despite the fact that rats withdrew from noxious heat (using either method of application) applied during sleep, the rats quickly returned to sleep afterwards. The latency to sleep after noxious stimulation was significantly greater during waking than during sleeping. The behavioral response to noxious thermal stimulation includes both an initial motor withdrawal which is enhanced during sleep and arousal or alerting which is suppressed during sleep. Therefore, pain evokes at least two distinct reactions that are differentially modulated across sleep/wake cycles. PMID- 11204052 TI - Postoperative sleep disturbance: influences of opioids and pain in humans. AB - STUDY OBJECTIVES: To test the hypothesis that opioids and pain contribute independently to postoperative sleep disturbance, 10 women undergoing surgery requiring a low abdominal incision for treatment of benign gynecologic conditions were randomized to receive either epidural opioid (fentanyl) (n=6) or epidural local anesthetic (bupivacaine) (n=4) for intraoperative and postoperative analgesia. DESIGN: N/A. SETTING: N/A. PATIENTS OR PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS: Polysomnography was performed in a standard patient room on the preoperative and first three postoperative nights. Pain at rest and with coughing was evaluated using a visual-analogue pain scale each evening and morning. RESULTS: On the first postoperative night, rapid eye movement (REM) sleep was abolished in all patients. On the third postoperative night, the mean +/- SE REM sleep time increased significantly (p=.003) to 9.8% +/ 3.1% in the fentanyl group, and 12.9% +/- 3.8% in the bupivacaine group. Conversely, light non-REM (NREM) sleep (%stage 1 + %stage 2) was higher on the first postoperative night and significantly lower on the third postoperative night (p=0.011). Between group comparison revealed only that the mean % slow-wave sleep (SWS) in the fentanyl group (6.0%, 2.0%, and 14.7%) was different from the bupivacaine group (7.8%, 9.1%, and 10.6%) in the postoperative period after adjusting for the preoperative night % SWS (p=0.021). Pain was well controlled in all patients, but was slightly better controlled in the fentanyl group than in the bupivacaine group on postoperative night 2 (p=0.024). There was no statistically significant association between pain score and any polysomnographically defined stage. CONCLUSION: Postoperative patients suffer a profound sleep disturbance even when opioids are avoided and pain is well controlled. PMID- 11204053 TI - Factors altering the sleep of burned children. AB - Although few studies have been conducted on burn patients, they indicate that sleep of burned children is altered. We suggest in this review, on the basis of the limited data available that factors contributing to sleep disruption in burned individuals may be broadly categorized as pathophysiological responses to the injury, the pain and discomfort experienced by the patient and medications used to treat these symptoms, and the physical environment in the Burns Intensive Care Unit. The responses to thermal injury include alterations in circulating neuropeptides, hormones, and immune-active substances, many of which are known to regulate/modulate sleep. Medications for the management of pain and for treating symptoms of various injury-induced stress and anxiety disorders may also alter sleep. Finally, frequent disruptions of the patient by medical staff is but one of the many environmental factors that may contribute to disrupted sleep. Severe burns induce a hypermetabolic response that may result in peripheral wasting, that depletes substrates necessary for tissue repair, and is associated with reduced growth hormone. Burn-induced growth hormone insufficiency is aggressively treated to counteract peripheral wasting and to aid in wound healing of skin graft donor sites. We speculate that improvement of sleep quality would result in a less severe reduction in growth hormone due to the well documented relationship between slow-wave sleep onset and growth hormone secretion. Such improvement in spontaneous growth hormone secretion patterns may aid in recovery by supporting tissue repair and by minimizing the hypermetabolic response to thermal injury. The experiments to test such hypotheses remain to be conducted, yet the results of such experiments may provide the basis for beginning to answer the question of whether or not sleep aids in recovery from injury. PMID- 11204054 TI - G protein activation in rat ponto-mesencephalic nuclei is enhanced by combined treatment with a mu opioid and an adenosine A1 receptor agonist. AB - STUDY OBJECTIVES: Opioids delivered to the pons inhibit REM sleep, whereas pontine administration of adenosine enhances REM sleep. In other brain areas opioids and adenosine interact to produce antinociception. Adenosine A1 receptors and mu opioid receptors each activate Gi/Go proteins. This study tested the hypothesis that combined treatment with the adenosine A1 receptor agonist SPA and the mu opioid agonist DAMGO would enhance G protein activation to a greater level than produced by either agonist alone. G protein activation was quantified in seven brainstem regions regulating sleep and nociception. This study also tested the hypothesis that G protein activation caused by SPA would be concentration dependent and blocked by the adenosine A1 receptor antagonist DPCPX. DESIGN: Activation of G proteins was assessed autoradiographically by agonist stimulation of [35S]GTPgammaS binding in slide-mounted sections of rat brainstem. G protein activation was quantified in nCi/g tissue for pontine reticular formation, dorsal raphe, ventrolateral and dorsomedial periaqueductal gray, and laterodorsal and pedunculopontine tegmental nuclei. SETTING: N/A. PATIENTS OR PARTICIPANTS: N/A. MEASUREMENTS AND RESULTS: Combined treatment with SPA and DAMGO caused a partially additive increase in G protein activation that was significantly (p<0.01) greater than G protein activation caused by either agonist alone. Treatment with SPA alone caused a concentration dependent (p<0.001) increase in [35S]GTPgammaS binding that was blocked by DPCPX. CONCLUSION: Agonist activation of adenosine A1 receptors stimulates G proteins in brainstem nuclei regulating sleep and nociception. In these same nuclei, G protein activation by combined treatment with DAMGO and SPA was partially additive, suggesting that mu opioid and adenosine A1 receptors activate some common G protein pools. PMID- 11204055 TI - Orexin (hypocretin)-like immunoreactivity in the cat hypothalamus: a light and electron microscopic study. AB - Orexin-A-like immunoreactive (OrA-ir) neurons and terminals in the cat hypothalamus were examined using immunohistochemical techniques. OrA-ir neurons were found principally in the lateral hypothalamic area (LHA) at the level of the tuberal cinereum and in the dorsal and posterior hypothalamic areas. In the LHA the majority of the neurons were located dorsal and lateral to the fornix; a small number of OrA-ir neurons were also present in other regions of the hypothalamus. OrA-ir fibers with varicose terminals were detected in almost all hypothalamic regions. The high density of fibers was located in the suprachiasmatic nucleus, the infundibular nucleus (INF), the tuberomamillary nucleus (TM) and the supra- and pre-mamillary nuclei. Ultrastructural analysis revealed that OrA-ir neurons in the LHA receive abundant input from non immunoreactive terminals. These terminals, which contained many small, clear, round vesicles with a few large, dense core vesicles, made asymmetrical synaptic contacts with OrA-ir dendrites, indicating that the activity of orexin neurons is under excitatory control. On the other hand, the terminals of OrA-ir neurons also made asymmetrical synaptic contact with dendrites in the LHA, the INF and the TM. The dendrites in the LHA were both non-immunoreactive and OrA-ir; conversely, the dendrites in the INF and the TM were non-immunoreactive. In these regions, OrA-ir terminals contained many small, clear, round vesicles with few large, dense core vesicles, suggesting that orexinergic neurons also provide excitatory input to other neurons in these regions. PMID- 11204056 TI - The investigation of K-complex and vertex sharp wave activity in response to mid inspiratory occlusions and complete obstructions to breathing during NREM sleep. AB - STUDY OBJECTIVES: To determine whether the cortical response to mid-inspiratory occlusions can be used as a model of the cortical response to obstructive events during sleep; and to determine whether the vertex sharp wave (VSW) and K-complex are exclusive contributors to the N350 and N550 components respectively of the stage 2 sleep event-related potential. DESIGN: Two types of respiratory stimuli were used to elicit evoked potential responses during stage 2 NREM sleep. These were mid-inspiratory occlusions and complete breath obstructions. Trials were grouped according to the type of phasic response elicited; isolated K-complex (KC), VSW associated with a K-complex (VSW/KC), isolated VSW, and no evoked response (other). Evoked responses were averaged separately within these categories. SETTING: Data were collected in the University of Melbourne Sleep Laboratory. PARTICIPANTS: Six young healthy male adults. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Data were recorded from 29 scalp sites referenced to linked ears. Mask pressure (Pm) and airflow were also recorded. Intra-thoracic pressure, as indicated by Pm, reached a more negative level following complete obstructions than brief occlusions. However, both types of respiratory stimuli elicited the two late latency components. Although latency varied across the two respiratory conditions in a manner consistent with the intra-thoracic pressure rise time differences, the elicitation characteristics and topographic distribution of these components did not vary across the two types of stimuli. In addition, an N350 was only present in the average for those categories that included VSWs, while an N550 was only present in those categories that contained K-complexes. CONCLUSIONS: Mid-inspiratory occlusions can be used as a model of obstructive events. VSWs contribute exclusively to the N350 component, while K complexes contribute exclusively to the N550 component. PMID- 11204057 TI - Effect of sleep position and sleep stage on the collapsibility of the upper airways in patients with sleep apnea. AB - Collapsibility of the upper airways has been identified as an important pathogenic factor in obstructive sleep apnea (OSA). Objective measures of collapsibility are pharyngeal critical pressure (Pcrit) and resistance of the upstream segment (Rus). To systematically determine the effects of sleep stage and body position we investigated 16 male subjects suffering from OSA. We compared the measures in light sleep, slow-wave sleep, REM sleep and supine vs. lateral positions. The pressure-flow relationship of the upper airways has been evaluated by simultaneous readings of maximal inspiratory airflow (Vimax) and nasal pressure (p-nCPAP). With two-factor repeated measures ANOVA on those 7 patients which had all 6 situations we found a significant influence of body position on Pcrit (p<0.05) whereas there was no significant influence of sleep stage and no significant interaction between body position and sleep stage. When comparing the body positions Pcrit was higher in the supine than in the lateral positions. During light sleep Pcrit decreased from 0.6 +/- 0.8 cm H2O (supine) to -2.2 +/- 3.6 cm H2O (lateral) (p<0.01), during slow-wave sleep Pcrit decreased from 0.3 +/- 1.4 cm H2O (supine) to -1.7 +/- 2.6 (lateral) (p<0.05) and during REM sleep it decreased from 1.2 +/- 1.5 cm H2O to -2.0 +/- 2.2 cm H2O (p<0.05). Changes in Rus revealed no body position nor sleep-stage dependence. Comparing the different body positions Rus was only significantly higher in the lateral position during REM sleep (p<0.05). The results indicate that collapsibility of the upper airways is not mediated by sleep stages but is strongly influenced by body position. As a consequence lower nCPAP pressure is needed during lateral positions compared to supine positions. PMID- 11204058 TI - The association of sleep-disordered breathing and sleep symptoms with quality of life in the Sleep Heart Health Study. AB - This study assessed the extent to which sleep-disordered breathing (SDB), difficulty initiating and maintaining sleep (DIMS), and excessive daytime sleepiness (EDS) were associated with impairment of quality of life (QoL) using the SF-36. Participants (n=5,816; mean age=63 years; 52.5% women) were enrolled in the nation-wide population-based Sleep Heart Health Study (SHHS) implemented to investigate sleep-disordered breathing as a risk factor in the development of cardiovascular disease. Each transformed SF-36 scale was analyzed independently using multiple logistic regression analysis with sleep and other potential confounding variables (e.g., age, ethnicity) included as independent variables. Men (11.6%) were significantly more likely to have SDB compared to women (5.6%), while women (42.4%) were significantly more likely to report DIMS than men (32.5%). Vitality was the sole SF-36 scale to have a linear association with the clinical categories of SDB (mild, moderate, severe SDB). However, individuals with severe SDB indicated significantly poorer QoL on several SF-36 scales. Both DIMS and EDS were strongly associated with reduced QoL even after adjusting for confounding variables for both sexes. Findings suggest 1) mild to moderate SDB is associated with reduced vitality, while severe SDB is more broadly associated with poorer QoL, 2) subjective sleep symptoms are comprehensively associated with poorer QoL, and 3) SF-36 mean score profiles for SDB and sleep symptoms are equivalent to other chronic diseases in the U.S. general population. PMID- 11204059 TI - Communication is often illusory. PMID- 11204060 TI - Argon laser curing of fluoride-releasing pit and fissure sealant: in vitro caries development. AB - The purpose of this study was to compare the effect of argon laser polymerization of a visible-light-cured, fluoride-releasing pit and fissure sealant on caries development in vitro. A total of twelve caries-free premolar and molar teeth was selected, and underwent a fluoride-free prophylaxis and soft tissue debridement. Cavity preparations were placed in buccal and lingual surfaces. Lingual cavity preparations were filled with the fluoride-releasing sealant (UltraSealXTplus, Ultradent) and visible light cured per the manufacturer's recommendation. Buccal preparations were filled with the fluoride-releasing sealant and argon laser cured (231 mW, 12 J/cm2 for 10 seconds). Following sealant placement, the teeth were sectioned into buccal and lingual halves. An acid-resistant varnish was placed leaving a 1 mm rim of exposed surface enamel adjacent to the sealant. The specimens were then thermocycled in synthetic saliva (500 cycles, 5 to 50 degrees C). In vitro caries lesions were formed (2.2 mM Ca, 2.2 mM PO4, 50 mM acetic acid, 5 ppm fluoride, pH 3.95). Longitudinal sections (five sections per tooth half) were obtained and evaluated by polarized light microscopy for mean outer surface lesion depths and frequency of wall lesions. Mean primary surface (outer) lesion depth was significantly decreased (ANOVA, DMR, P < .05) for the fluoride releasing sealant with argon laser polymerization (152 +/- 16 um) when compared with visible light curing (211 +/- 23 um). Likewise, wall lesion frequency was substantially reduced for the argon laser polymerized sealants (17 percent) when compared with that for the visible light polymerized sealants (24 percent, ANOVA, DMR, P < .05). Argon laser polymerization of a fluoride-releasing pit and fissure sealant improved caries resistance markedly in the surface enamel adjacent to the sealant material. Argon laser curing enhanced the caries protective ability of the sealant along the enamel-resin cavosurface, as noted by a decrease in wall lesion frequency. Argon laser polymerization provides further caries protection against a cariogenic challenge over that afforded by fluoride-releasing sealants. Caries development around a sealant material may be hampered by the combination of fluoride release from the sealant and argon laser polymerization. PMID- 11204061 TI - Vitremer restorative cement for children: three clinicians' observations in three pediatric dental practices. AB - BACKGROUND: The authors retrospectively evaluated the clinical performance of a resin-modified glass ionomer cement as a Class I, Class II, Class III, and Class V restorative material in primary teeth. METHODS: Three hundred and six patients that had received 864 resin-modified glass ionomer restorations, which had been in the mouth for a minimum of three years, were included in this evaluation. RESULTS: The results demonstrated an overall 93.4 percent restoration success rate, Class I restorations presenting a 92.6 percent success. Class II restorations presenting a 93.4 percent success, Class III restorations presenting a 100 percent success and Class V restorations presenting a 98 percent success, respectively. CONCLUSIONS: The resin-modified glass ionomer cement functioned well as a Class I, Class II, Class III, and Class V restorative material in the primary dentition. CLINICAL IMPLICATIONS: Resin-modified glass ionomer cement restorative material functions well for Class I, Class II, Class III, and Class V restorations in primary teeth. PMID- 11204062 TI - Chlorhexidine varnishes prevent gingivitis in adolescents. AB - BACKGROUND: Chlorhexidine, a cationic anti-microbial agent, prevents gingivitis by inhibiting plaque accumulation. Gingivitis is the most predominant form of periodontal disease in children and adolescents. The purpose of this study was to determine the effects of a chlorhexidine varnish on the gingival status of adolescents. METHODS: The subjects of this study were 10-15 years old adolescents randomly divided into a control (C) and a treatment (T) group, n = 53 and n = 57, respectively. After restoration of all caries lesions, a prophylaxis was given to both C and T groups. A 10 percent chlorhexidine varnish was applied to the entire dentition of T subjects at BL; and one week and three months thereafter. One calibrated examiner determined blindly the Gingival Index (GI) of all subjects. RESULTS: The average percentage of sites per subject with GI scores of 2 or 3 at BL, and after three and six months for the T group were, respectively, 3.68 +/- 7.13, 0.71 +/- 2.43 and 0.16 +/- 0.62. The corresponding values for the C group were 2.11 +/- 3.68, 1.27 +/- 2.94 and 1.59 +/- 5.20. Profile analysis revealed that over a 6-month period subjects of T group had significantly fewer sites with GI scores 2 and 3 than subjects in the C group (p = 0.025). CONCLUSIONS: It is concluded that the professional application of a chlorhexidine varnish significantly improved the gingival health of adolescents over a 6-month period. PMID- 11204063 TI - Histomorphologic changes in the gingiva and pulp of overretained primary teeth. AB - This study examined the influence of overretention on the tissues of human primary teeth. The range of overretention was two to thirty-two years. Light microscopy and computerized morphometry were utilized for histologic assessment of twenty-five sites of twenty-one teeth. Dentinoclasts were found on the resorbing root surface of nine teeth; polymorphonuclear leucocytes were found in the pulp of fourteen teeth; and monocytes were present in all pulps. The apical and coronal ends of the junctional epithelium were apical to the cemento-enamel junction in eighteen and fourteen teeth, respectively. Significant correlations were found between the extent of overretention and gingival height, the length of the junctional epithelium and the extent of apical migration of the junctional epithelium. Present and previous findings indicate that odontoclastic activity in the pulp is reduced with overretention; and while at the beginning of overretention there is a lower percentage of pulps with polymorphonuclear leucocytes in the pulp, with an extended period of overretention an increase in this percentage takes place. PMID- 11204064 TI - Caries prediction and indicators using a pediatric risk assessment teaching tool. AB - The goals of this study were to determine both predictability and risk indicators in a young pediatric population seen in a dental school clinic using a Caries Risk Assessment teaching tool. Assigned risk categories and factors for 140 patients were analyzed for relationships with future caries development using Logistic Regression (p < 0.01) and Chi-square analysis (p < 0.05). Among the group developing caries, variables and disease were analyzed using ANOVA Independent Samples Test (p < 0.05). Assigned-risk categories were significantly predictive with odds ratios (OR) of Moderate- and High-risk developing new caries being 5.41 and 28.64 respectively when compared with Low-risk. Significant risk indicators were diet, oral hygiene and the presence of caries and decalcifications. The risk assessment tool used in this study predicted future caries development. Through this method of assessment, caries risk indicators in the population studied were determined to be diet, oral hygiene and past caries experience. PMID- 11204065 TI - Deinstitutionalization of children with mental retardation: what of dental services? AB - During the past thirty years there has been marked deinstitutionalization from large state facilities for youngsters and adults with mental retardation and developmental disabilities. In the past, dental (and general medical) services were provided in the institutions by an in-house staff. Increased numbers of former residents now live in small community units. These local residents must now rely on community dental practitioners for needed preventive and restorative services. The current status of these services (or lack there of) is reviewed, together with relevant concerns. PMID- 11204066 TI - Dentist participation in a public-private partnership to increase Medicaid participation and access for children from low income families. AB - The purpose of this research is to solicit feedback from dental society members involved in a program (Access to Baby and Child Dentistry, ABCD) to provide care for children receiving Medicaid benefits, and to gain an understanding of dentist participation. We investigated whether general dentists who were participants in ABCD were more fully integrated into the dental society profession and community, and whether they demonstrated greater interest in children. Dentists were stratified regarding ABCD participation and randomly selected to be interviewed (N = 40). The majority thought it appropriate for general dentists to care for very young children. Participants found fewer problems in fee levels in Medicaid, but there was no difference in an index of fees between the groups. Participants were no more active in the dental society, and few differences existed between the groups regarding other aspects of personal or professional life. Dentists participating in ABCD to improve access had a good experience and have positive views of the program. This may encourage other nonspecialist colleagues to participate in programs for children. PMID- 11204067 TI - Dentists' ranking of Medicaid reimbursement rates as a measure of their pediatric Medicaid participation. AB - The objective of the study was to determine the usefulness of dentists' ranking of Medicaid reimbursement rates as a measure of their participation in the Medicaid program for children. Data were obtained from two mail-in questionnaire surveys of Connecticut dentists, before and after an increase in Medicaid reimbursement rates for children. Dentists ranked acceptability of Medicaid reimbursement rates on a seven-point index, while their participation in the Medicaid program was assessed by whether they acknowledged treating Medicaid children and were currently accepting new Medicaid children into their practices. There was a significant difference (p < 0.0001) in the dentists' ranking of Medicaid reimbursement rates following the rate increase indicating that the index was responsive. Acceptance of new Medicaid children into dental practices was a better measure of active participation in the Medicaid program. Following the increase in Medicaid reimbursement rates, dentists ranking it as acceptable/equivocal were more likely (p < 0.02) to accept new Medicaid children into their practices. In conclusion, the index of dentists' ranking of Medicaid reimbursement rates was a responsive and valid measure of their participation in the Medicaid program. PMID- 11204068 TI - Would you believe that during the 1990s, applications to pediatric dental training programs more than doubled? AB - A review of application to (and enrollment in) pediatric dental programs indicates increasing dental student graduate interest (particularly by female graduates) in this specialty. Except for black student representation, enrollment in pediatric dentistry training programs increasingly represents the ethnic and racial distribution of the general population. PMID- 11204069 TI - Impaired dentofacial development after radiotherapy of a non-Hodgkin lymphoma: report of case. AB - Since the advances in therapy of childhood malignancies have improved life expectancy attention is now increasingly focused on the long-term effects of antineoplastic therapy. Developmental abnormalities due to antineoplastic therapy have been claimed to preferentially occur in children treated before the age of six years. This report of a case demonstrates severe developmental disturbances following radiotherapy of a cervical non-Hodgkin lymphoma at the age of eight years. The morphological changes included microdontia, root shortening, blunting and thinning as well as mandibular hypoplasia. PMID- 11204070 TI - Dental findings in Morquio syndrome (mucopolysaccharidoses type IVa). AB - Morquio syndrome is a disorder of mucopolysaccharide metabolism with specific skeletal features. The clinical and radiographic appearance of the teeth resembles hypoplastic amelogenesis imperfecta with thin enamel of normal radiodensity. The dental practitioner has a part to play in collaboration with medical colleagues in the recognition and diagnosis of this condition. PMID- 11204071 TI - Concealed accessory pathway with long conduction times and incremental properties: a case report. AB - Concealed AP with Slow and Incremental Conduction. We report a peculiar form of permanent junctional reciprocating tachycardia that occurs only during daytime and physical activity. ECG obtained during tachycardia showed an unusual progressive shortening of the ventriculoatrial (VA) interval that was maximal at the first complex and shortest at the last one before block occurred, always at the accessory pathway level. This phenomenon has not been previously described and appears to be a reverse type of Wenckebach block. It was observed during salvos of spontaneous tachycardia and could be reproduced by right ventricular pacing. The accessory pathway was ablated successfully at the right posteroseptal region, close to the coronary sinus ostium. After ablation, there was no VA conduction, and tachycardia did not recur during a 9-month follow-up period. PMID- 11204072 TI - Vasospastic angina accompanied by Brugada-type electrocardiographic abnormalities. AB - Brugada Syndrome and Vasospastic Angina. We present two patients with vasospastic angina and Brugada-type ECG abnormalities. The first patient complained of chest pain, and transient ST segment elevation was confirmed on ECG. Coronary angiogram showed no organic stenosis. The second patient had syncopal episodes following anginal chest pain, and the same symptoms were reproduced by intracoronary acetylcholine injection that induced vasospasm. In both patients, ECG at rest showed ST segment elevation in leads V1 and V2 and a right bundle branch block pattern that were accentuated by a Class I antiarrhythmic drug. Ventricular fibrillation also was induced by programmed electrical stimulation. Susceptibility to ventricular fibrillation can be modulated by the interaction of coronary vasospasm with Brugada syndrome or vice versa; therefore, it is important to study the clinical implications of the coexistence of the two diseases in such patients. PMID- 11204073 TI - Prevention of sudden death in heart failure. PMID- 11204074 TI - A long RP tachycardia: what is the tachycardia mechanism? PMID- 11204075 TI - Intracardiac tuberculoma causing "idiopathic" ventricular tachycardia in a patient without detectable heart disease. PMID- 11204076 TI - High incidence of focal atrial fibrillation (AF) from the right atrium (RA). PMID- 11204077 TI - How do I prolong QT? Let me count the ways. PMID- 11204078 TI - Electroanatomic characterization of conduction barriers in sinus/atrially paced rhythm and association with intra-atrial reentrant tachycardia circuits following congenital heart disease surgery. AB - INTRODUCTION: The electrophysiologic mechanism of intra-atrial reentrant tachycardia (IART) is generally thought to be a macroreentrant circuit revolving around a nonconductive or highly anisotropic barrier. However, the electrical and anatomic substrate that supports these circuits has been incompletely defined. Our objectives were to characterize the atria of patients with IART using electroanatomic mapping in sinus or atrially paced rhythm and to determine whether electrical barriers identified in sinus/atrially paced rhythm are associated with IART circuits. METHODS AND RESULTS: Eighteen patients with IART and a remote history of repaired or palliated congenital heart disease were studied [8 biventricular repair, 8 single ventricle palliation (7 Fontan), and 2 Mustard repair]. Thirteen patients had a right AV valve. In sinus/atrially paced rhythm, electrical evidence of a crista terminalis was identified in 11 patients, an atriotomy in 12, and > or = 1 right atrial free-wall scar in 11. In 26 IART circuits characterized, 12 used the right AV valve as a central obstacle, 6 used a right atrial free-wall scar, 3 used an atriotomy, 3 used the crista terminalis, and 2 circuits used an atrial septal scar. All central obstacles used by IART circuits were identified in sinus/atrially paced rhythm. CONCLUSION: The crista terminalis, atriotomy, and right atrial scars can be identified in patients with repaired congenital heart disease by electroanatomic mapping in sinus/atrially paced rhythm. These conduction barriers frequently function as the central obstacle for IART. Demonstration of such features may help focus investigational mapping without reliance on spontaneous initiation of the tachycardia. PMID- 11204079 TI - Relatively benign clinical course in asymptomatic patients with brugada-type electrocardiogram without family history of sudden death. AB - INTRODUCTION: The incidence of sudden death or ventricular fibrillation (VF) in asymptomatic Brugada syndrome patients with a family history of sudden death is reported to be very high. However, there are few reports on the prognosis of asymptomatic Brugada syndrome patients without a family history of sudden death. METHODS AND RESULTS: Eleven patients (all male; mean age 40.5 +/- 9.6 years, range 26 to 56) with asymptomatic Brugada-type ECG who had no family history of sudden death were evaluated. The degrees of ST segment elevation and conduction delay on signal-averaged ECG (SAECG) before and after pilsicainide were evaluated in all 11 patients. VF inducibility by ventricular electrical stimulation also was evaluated in 8 of 11 patients. Patients were followed for a period of 9 to 84 months (mean 42.5 +/- 21.6). The J point level was increased (V1: 0.19 +/- 0.09 mV to 0.36 +/- 0.23 mV; V2: 0.31 +/- 0.12 mV to 0.67 +/- 0.35 mV) by pilsicainide. Conduction delay was increased (total QRS: 112.2 +/- 6.3 msec to 131.7 +/- 6.3 msec; under 40 microV: 42.0 +/- 8.5 msec to 52.7 +/- 12.7 msec; last 40 msec: 17.4 +/- 5.9 microV to 10.4 +/- 6.1 microV) on SAECG by pilsicainide. VF was induced in only 1 of 8 patients. None of the patients had syncope or sudden death during a mean follow-up of 42.5 +/- 21.6 months. CONCLUSION: This study suggests that asymptomatic patients with Brugada-type ECG who have no family history of sudden death have a relatively benign clinical course. PMID- 11204080 TI - Reversal of deteriorated fractal behavior of heart rate variability by beta blocker therapy in patients with advanced congestive heart failure. AB - INTRODUCTION: The slope of the power spectrum in heart rate variability (HRV) reflects the fractal or scaling behavior in HR dynamics and recently was confirmed as an independent predictor of postmyocardial infarction survival. Whether or not the new measurement in HRV foresees the functional evolution in patients with advanced congestive heart failure treated by beta blockers is unclear. METHODS AND RESULTS: Sequential 24-hour Holter ECG recordings were obtained at baseline, and 1 and 3 months after addition of atenolol therapy for advanced congestive heart failure in 10 patients. The slope and intercept of the regression line of power-law behavior, the short- and intermediate-term of detrended fluctuated analysis (DFA), the approximate entropy (ApEn), and the standard frequency spectra of the 24-hour HRV were compared sequentially as well as with those in 12 age-matched normal controls. The results showed that the slope (-1.70 +/- 0.45 vs -1.22 +/- 0.21; P < 0.05) and the intercept (5.11 +/- 0.46 vs 5.62 +/- 0.24; P < 0.05) of the regression line of power-law behavior and the short-term DFA (for 4 to 11 beats) (0.78 +/- 0.18 vs 1.13 +/- 0.21; P < 0.05) increased after 3 months of atenolol treatment. However, the change in intermediate-term DFA (>11 beats) and ApEn was not apparent (1.24 +/- 0.21 vs 1.22 +/- 0.15 and 1.34 +/- 0.14 vs 1.36 +/- 0.11; both P > 0.05). The evolution of the slope or intercept of the regression line of the HRV power spectrum did not correlate with the echocardiographic or clinical cardiac function, or with the frequency spectral components of the HRV (P > 0.05). CONCLUSION: Additional beta-blocker therapy upregulated the fractal behavior control of the HRV in patients with advanced congestive heart failure. The improvement was independent of subjective and objective global cardiac performance. PMID- 11204081 TI - Broken fractals: where's the break? PMID- 11204082 TI - Differential modulation of electrocardiographic indices of ventricular repolarization dispersion depending on the site of pacing during premature stimulation. AB - INTRODUCTION: Dispersion of ventricular repolarization has been shown to increase with premature stimulation. Moreover, a straight correlation between the amount of dispersion of repolarization and the vulnerability to ventricular fibrillation was reported. On the other hand, differences between right ventricular (RV) and left ventricular (LV) fibrillation threshold have been reported. However, no data exist regarding the influence of the site of stimulation on modulation of dispersion of repolarization. METHODS AND RESULTS: In the present study, several ECG indices of dispersion of repolarization, as a function of the coupling interval and the site of stimulation, were evaluated in a modified Langendorff perfused rabbit heart (n = 12), with a 5 x 8 array of a simulated body surface unipolar lead system. As the coupling interval was shortened, a biphasic modulation of dispersion of repolarization was found when stimuli were elicited at the LV. In contrast, when the heart was paced from the RV, the dispersion increased monotonically as coupling interval was shortened. CONCLUSION: A differential behavior of the modulation of dispersion of repolarization was found as a function of the site of stimulation. PMID- 11204083 TI - Effects of simultaneous atrioventricular pacing on atrial refractoriness and atrial fibrillation inducibility: role of atrial mechanoelectrical feedback. AB - INTRODUCTION: The purpose of this study was to evaluate the effects of an acute increase in atrial pressure on refractoriness (mechanoelectrical feedback) and the vulnerability to atrial fibrillation (AF) and to investigate the effects of autonomic blockade and verapamil on mechanoelectrical feedback in humans. METHODS AND RESULTS: Right atrial pressure and effective refractory period (ERP) at the right atrial appendage (RAA) and high right atrial septum were measured during sinus rhythm, and during atrial and simultaneous AV pacing at a cycle length of 300 msec, either in the absence (n = 25) or presence (n = 22) of pharmacologic autonomic blockade. In another 15 patients, the protocol was performed before and after infusion of verapamil 0.15 mg/kg. In the absence of autonomic blockade, AV pacing resulted in a higher mean right atrial pressure (11.7 +/- 3.3 vs 4.3 +/- 3.0 mmHg, P < 0.001) and a shorter atrial RAA ERP (144 +/- 23 msec vs 161 +/- 21 msec; P < 0.001) compared with atrial pacing; AF was induced more often during AV pacing (87%) than during atrial pacing (20%) and was related directly to the right atrial pressure (r = 0.39, P = 0.004) and indirectly to the RAA ERP (r = 0.42, P < 0.001). The susceptibility to sustained AF was greatly enhanced by autonomic blockade. Verapamil markedly attenuated the shortening of ERP and the propensity for AF that occurred during simultaneous AV pacing. CONCLUSION: An acute increase in atrial pressure during tachycardia is associated with shortening of atrial refractoriness and a propensity for AF, i.e., atrial mechanoelectrical feedback, which may be enhanced by autonomic blockade and attenuated by calcium channel blockade. PMID- 11204084 TI - Electrical remodeling of the atria as a consequence of atrial stretch. PMID- 11204085 TI - Late occurrence of heart block after radiofrequency catheter ablation of the septal region: clinical follow-up and outcome. AB - INTRODUCTION: There are few data regarding the occurrence of delayed heart block at least 24 hours after radiofrequency catheter ablation (RFCA) of AV nodal reentry or posteroseptal accessory pathways (APs). We investigated the late occurrence of heart block in this population, the clinical outcome, and whether findings at electrophysiologic study could have predicted its development. METHODS AND RESULTS: Two of 418 patients with AV nodal reentry undergoing RFCA using a posterior approach and 1 of 54 patients with RFCA of a posteroseptal AP developed late heart block. Anterograde and retrograde AV nodal conduction before and after RFCA were normal. Patients received 12, 15, and 32 RFCA lesions, respectively, using a mean maximum power of 44 W. The RFCA sites were the posterior septum for posteroseptal AP and the posterior and mid-septum for patients with AV nodal reentry, with no His electrogram ever recorded at the ablation site. During RFCA, junctional tachycardia occurred with 1:1 VA conduction in the patient with a posteroseptal AP, but occasional intermittent single retrograde blocked complexes were present in both patients with AV nodal reentry. No rapid junctional tachycardia or >1 consecutive retrograde blocked complex was ever observed during RFCA. Persistent high-degree AV block with junctional escape developed 2 days after RFCA in the posteroseptal AP patient. A permanent pacemaker was implanted, and normal conduction was noted 16 days after RFCA. Both patients with AV nodal reentry complained of fatigue, mainly on exertion, 3 to 4 days after RFCA, and ECG-documented exercise-induced variable AV block was obtained. Because heart block resolved in our initial patient, a prolonged monitoring period was allowed. Symptoms disappeared at 13 and 8 days, and a follow-up treadmill test showed normal PR interval and no heart block. No recurrence of heart block has been seen in any of these three patients. CONCLUSION: Late unexpected heart block after RFCA of AV nodal reentry and posteroseptal AP is rare, often resolves uneventfully in 1 to 2 weeks, and no specific electrophysiologic findings predicted its occurrence. Prolonged clinical observation is preferable to immediate pacemaker implantation in such patients. PMID- 11204087 TI - Role of structural complexities of septal tissue in maintaining ventricular fibrillation in isolated, perfused canine ventricle. AB - INTRODUCTION: It is unclear how the patterns of wavelet propagation during ventricular fibrillation (VF) vary between structurally different tissues. We hypothesized that the structural complexities of septal tissue influence the maintenance of reentrant wavelets in the ventricle. METHODS AND RESULTS: Endocardial activation patterns during VF were analyzed in the isolated, perfused canine right ventricular (RV) free wall (n = 9), interventricular septum (n = 5), and left ventricular (LV) free wall (n = 6) using a computerized mapping system (2-mm resolution) with 120-msec consecutive windows. Each tissue sample was cut progressively to reduce the tissue mass until the VF was terminated. More wavelets were seen in the septa than in the RV and LV free walls at baseline (P = 0.004), and VF in the septa displayed a shorter cycle length than in the RV and LV free walls (P = 0.017). As the tissue mass decreased, VF became successively more organized in all regions: the number of wavelets decreased and the cycle length of VF lengthened. Single and "figure-of-eight" stationary, reentrant wavelets often were mapped after tissue mass reduction in the RV free walls and rarely in the LV free walls, but they were not observed in the septa. Less critical mass was required to maintain VF in the septa than in the RV and LV free walls (P = 0.0006). Gross anatomic and histologic examinations indicated that the tissue structure of the septa is more complex than that of the RV and LV free walls. CONCLUSION: VF activation patterns with progressive reduction of tissue mass differ for the septum and the ventricular free walls. The structural complexities of the septal tissue influence the maintenance of fibrillation in the ventricle. PMID- 11204086 TI - Transient ST segment elevation in right precordial leads induced by psychotropic drugs: relationship to the Brugada syndrome. AB - Psychotropic Drugs and ST Segment Elevation. Transient ST segment elevation in right precordial leads with use of psychotropic drugs is reported in two cases of overdose and one case of therapeutic administration. Flecainide did not reproduce ST segment elevation. The relationship of these abnormalities to the Brugada syndrome and the electrophysiologic hypothesis are discussed. PMID- 11204088 TI - Asymptomatic patients with a brugada electrocardiogram: are they at risk? PMID- 11204089 TI - Pacing during ventricular fibrillation: factors influencing the ability to capture. AB - INTRODUCTION: Recent studies showed that pacing atrial and ventricular fibrillation (VF) is possible. The studies presented here determined which parameters influence the efficacy of a pacing train to capture fibrillating ventricular myocardium. Electrode type, current strength, order of pacing trains, polarity, and VF morphology preceding the pacing trains were investigated. METHODS AND RESULTS: A 504-electrode recording plaque sutured to the right ventricle of pig hearts was used to record the activations of VF and those resulting from the pacing stimulation. Capture of VF by pacing was determined by observing an animated display of the first temporal derivative of the electrograms. A series of electrodes in a line captured the heart more frequently during VF than did a point electrode. Increasing the current strength to 10 x diastolic pacing threshold increased the incidence of capture, but increasing this strength further did not. The second or third train of 40 stimuli had greater capture rates than did the first train during the same VF episode. Anodal and cathodal unipolar, and bipolar stimulation were equally efficacious in capturing VF. VF activation during the 1-second interval preceding pacing was more organized for pacing trains that captured than those that did not. The highest incidence of capture, 46% to 61% of pacing trains, occurred with a line of electrodes at 10 x diastolic pacing threshold delivered by the second or third train. CONCLUSION: The probability of a pacing train capturing fibrillating myocardium can be influenced by the pacing protocol parameters. PMID- 11204090 TI - Verapamil prevents stretch-induced shortening of atrial effective refractory period in langendorff-perfused rabbit heart. AB - INTRODUCTION: Atrial dilation and rapid pacing reduce atrial effective refractory periods (AERPs), thereby increasing the susceptibility to sustained atrial fibrillation (AF) in Langendorff-perfused rabbit hearts. It is unclear whether similar pathophysiologic mechanisms are operative in short-term electrophysiologic changes caused by dilation and rapid pacing. Therefore, we analyzed whether both forms of short-term electrophysiologic changes are similarly affected by pharmacologic interventions acting on different potential mechanisms underlying these changes. METHODS AND RESULTS: Thirty Langendorff perfused rabbit hearts underwent a protocol with stepwise increase of intra atrial pressure from 0 to 12 cm H2O followed by 10 minutes of rapid pacing at 4 cm H2O. The protocol was repeated after addition of glibenclamide (10 micromol/L, n = 7), cariporide (1 micromol/L, n = 7), or verapamil (1 micromol/L, n = 9). In the basal state, increase of intra-atrial pressure from 0 to 12 cm H2O decreased AERPs from 85 +/- 11 to 55 +/- 9 msec (P < 0.01), rapid pacing at low intra atrial pressure (4 cmH2O) decreased AERP to a similar extent, from 81 +/- 11 to 60 +/- 10 (P < 0.01). At higher intra-atrial pressure, decrease of AERP was more pronounced (10 cm H2O: 37 +/- 2 msec) (n = 7). Addition of verapamil decreased basal AERP from 86 +/- 10 msec to 68 +/- 11 msec (P < 0.05). Short-term electrophysiologic changes due to atrial dilation were abolished; changes due to rapid pacing were reduced but still present. Glibenclamide and cariporide had no significant effect. CONCLUSION: Langendorff-perfused rabbit heart is a suitable model for studying short-term electrophysiologic changes due to both rapid pacing and atrial dilation. AERPs are shortened to a similar extent by both mechanisms, whereas a combination of the two leads to more pronounced AERP reduction. Calcium overload plays a crucial role in short-term electrophysiologic changes caused by atrial dilation, whereas atrial ischemia or acidosis has no significant impact. PMID- 11204091 TI - Sympathetic activation enhances QT prolongation by quinidine. AB - INTRODUCTION: Salt restriction results in endogenous sympathetic activation, and we previously showed that plasma concentrations of quinidine measured after oral drug administration are increased during a low-salt diet. However, it is not known whether, independent of effects on plasma concentration, the extent to which quinidine prolongs the QT interval also is modulated by changes in endogenous sympathetic activity. METHODS AND RESULTS: In these studies, we evaluated quinidine concentration-QT relations during low-salt (10 mEq/day for 8 days) and high-salt (400 mEq/day for 8 days) diets, with or without beta blockade in normal volunteers. In the absence of beta blockade, the concentration producing a fixed (15%) increase in QTc was significantly lower with salt restriction: 1.2 +/- 0.4 microg/mL (low salt) versus 2.2 +/- 0.4 microg/mL (high salt) (P < 0.01). With beta blockade, this difference was abolished: 1.9 +/- 0.3 microg/mL (low salt + beta blockade) versus 2.1 +/- 0.3 microg/mL (high salt + beta blockade). QT morphologic abnormalities including bifid T waves and U waves were abolished with beta-adrenergic blockade. CONCLUSION: Sympathetic activation by a low-salt diet not only modulates drug disposition but also increases sensitivity to drug-induced QT prolongation. PMID- 11204093 TI - Sequential effects in naming: a time-criterion account. AB - S. J. Lupker, P. Brown, and L. Colombo (1997) reported that target naming latencies are strongly affected by the difficulty of the other stimuli in a trial block, an effect they attributed to readers' strategic use of a time criterion to guide responding. In the present research, the authors asked whether there are also trial-by-trial ("sequential") effects by examining naming latency as a function of the difficulty of the preceding stimulus. In Experiment 1, both nonwords and high-frequency regular words were named more rapidly following a word than a nonword. Experiments 2, 3, and 4 were parallel experiments involving a variety of stimulus types (e.g., high- and low-frequency inconsistent words, easy and hard nonwords). In all cases, similar sequential effects were observed (i.e., all stimulus types had shorter latencies following an easier-to-name than a harder-to-name stimulus). In terms of the time-criterion account, criterion placement appears to be affected by the relative difficulty of the preceding stimulus in a way that is independent of stimulus type. PMID- 11204092 TI - Species plays an important role in drug-induced prolongation of action potential duration and early afterdepolarizations in isolated Purkinje fibers. AB - INTRODUCTION: Although isolated Purkinje fibers (PFs) often are used to evaluate the electrophysiologic effects of new drugs in terms of prolongation of action potential duration (APD) and induction of early afterdepolarizations (EADs), species differences in this respect remain elusive. We evaluated potential species-specific differences in drug-induced prolongation of APD and EADs in isolated PF from various species. METHODS AND RESULTS: Using a microelectrode technique, PFs (n = 7 to 11 per species) were isolated from hearts of rabbits, guinea pigs, dogs, swine, goats, or sheep, superperfused in Tyrode's solution with dofetilide (1 x 10(-8) M) or quinidine (1 x 10(-5) M) for 25 minutes, and stimulated at 1 Hz for 20 minutes and at 0.2 Hz for another 5 minutes. Dofetilide increased APD at 90% repolarization (APD90) at 1 Hz by 83% (rabbit), 24% (guinea pig), 65% (dogs), 18% (swine), 61% (goat), and 30% (sheep), and prolonged APD90 at 0.2 Hz by 187% (rabbit), 31% (guinea pig), 154% (dog), 17% (swine), 61% (goat), and 8% (sheep). Similarly, quinidine changed APD90 by 93% (rabbit), 0% (guinea pig), 16% (dog), -3% (swine), 0% (goat), and -24% (sheep) at 1 Hz, and by 124% (rabbit), 15% (guinea pig), 53% (dog), 17% (swine), 11% (goat), and -39% (sheep) at 0.2 Hz in PF. During superfusion of dofetilide or quinidine, EADs occurred in most preparations in rabbit PFs at 0.2 Hz, but not in any of the PFs from other species at 0.2 Hz. CONCLUSION: Our study demonstrates that species plays an important role in the response of PF to drug-induced prolongation of APD and EADs. Rabbit PFs constitute the most sensitive model for detecting drug induced, potential long APD and proarrhythmogenic effects in vitro. PMID- 11204094 TI - Homophone effects in lexical decision. AB - The role of phonology in word recognition was investigated in 6 lexical-decision experiments involving homophones (e.g., MAID-MADE). The authors' goal was to determine whether homophone effects arise in the lexical-decision task and, if so, in what situations they arise, with a specific focus on the question of whether the presence of pseudohomophone foils (e.g., BRANE) causes homophone effects to be eliminated because of strategic deemphasis of phonological processing. All 6 experiments showed significant homophone effects, which were not eliminated by the presence of pseudohomophone foils. The authors propose that homophone effects in lexical decision are due to the nature of feedback from phonology to orthography. PMID- 11204095 TI - The discrepancy-attribution hypothesis: II. Expectation, uncertainty, surprise, and feelings of familiarity. AB - In the accompanying article (B. W. A. Whittlesea & L. D. Williams, 2001), surprising violation of an expectation was observed to cause an illusion of familiarity. The authors interpreted that evidence as support for the discrepancy attribution hypothesis. This article extended the scope of that hypothesis, investigating the consequences of surprising validation of expectations. Subjects were shown recognition probes as completions of sentence stems. Their expectations were manipulated by presenting predictive, nonpredictive, and inconsistent stems. Predictive stems caused an illusion of familiarity, but only when the subjects also experienced uncertainty about the outcome. That is, as predicted by the discrepancy-attribution hypothesis, feelings of familiarity occurred only when processing of a recognition target caused surprise. The article provides a discussion of the ways in which a perception of discrepancy can come about, as well as the origin and nature of unconscious expectations. PMID- 11204096 TI - Telling stories: the perils and promise of using verbal reports to study math strategies. AB - The problem size effect in adult arithmetic performance is generally attributed to direct retrieval processes operating on a network representation in long-term memory. J. LeFevre and her colleagues (J. LeFevre, J. Bisanz, et al., 1996; J. LeFevre, G. S. Sadesky, & J. Bisanz, 1996) challenged this explanation using verbal report evidence that adults also use time consuming nonretrieval strategies to solve simple addition and multiplication. The authors replicated J. LeFevre and colleagues' methods, but added instructional biasing and silent control conditions to test these methods. Both reaction time and report results suggest that LeFevre and colleagues' conclusions about nonretrieval frequency may have been influenced by instructions that revealed the experimental hypothesis and affected participants' strategy reports. Obtaining evidence about adult strategy use in simple arithmetic will require understanding instructional demand and appropriate report methodology. PMID- 11204097 TI - Information processing and insight: a process model of performance on the nine dot and related problems. AB - The 9-dot problem is widely regarded as a difficult insight problem. The authors present a detailed information-processing model to explain its difficulty, based on maximization and progress-monitoring heuristics with lookahead. In Experiments 1 and 2, the model predicted performance for the 9-dot and related problems. Experiment 3 supported an extension of the model that accounts for insightful moves. Experiments 4 and 5 provided a critical test of model predictions versus those of previous accounts. On the basis of these findings, the authors claim that insight problem solving can be modeled within a means-ends analysis framework. Maximization and progress-monitoring heuristics are the source of problem difficulty, but also create the conditions necessary for insightful moves to be sought. Furthermore, they promote the discovery and retention of promising states that meet the progress-monitoring criterion and attenuate the problem space. PMID- 11204098 TI - Meaning and modality: influences of context, semantic memory organization, and perceptual predictability on picture processing. AB - Using event-related potentials (ERPs), the authors investigated the influences of sentence context, semantic memory organization, and perceptual predictability on picture processing. Participants read pairs of highly or weakly constraining sentences that ended with (a) the expected item, (b) an unexpected item from the expected semantic category, or (c) an unexpected item from an unexpected category. Pictures were unfamiliar in Experiment 1 but preexposed in Experiment 2. ERPs to pictures reflected both contextual fit and memory organization, as do ERPs to words in the same contexts (K. D. Federmeier & M. Kutas, 1999). However, different response patterns were observed to pictures than to words. Some of these arose from perceptual predictability differences, whereas others seem to reflect true modality-based differences in semantic feature activation. Although words and pictures may share semantic memory, the authors' results show that semantic processing is not amodal. PMID- 11204099 TI - Learning new word meanings from context: a study of eye movements. AB - This study examined how readers establish the meaning of a new word from the sentence context during silent reading. Readers' eye movements were monitored while they read pairs of sentences containing a target word, context, and a word related to the target word. The target word varied in familiarity (high, low, or novel). The context varied in informativeness about the meaning of the target word (informative or neutral). The amount of time readers spent on the context depended on both the familiarity of the target word and the informativeness of the context. Readers spent additional time on the related word only when the context was neutral and the target was novel. These results indicate that readers were able to determine which areas of text were relevant and used the information to infer a meaning for the novel word. PMID- 11204100 TI - Relation and lexical priming during the interpretation of noun-noun combinations. AB - This research indicates that recent exposure to a similar combination (e.g., oil moisturizer or surgery treatment) influences the processing of a subsequent combination (e.g., oil treatment) by increasing the availability of the lexical entries for the modifier and head noun, and by altering the availability of the relation used to link the two nouns. The amount of lexical and relational priming obtained depends on whether the modifier or head noun is in common between the prime and target. The head noun prime yields more lexical priming than does the modifier prime and this finding suggests that the head noun is more strongly activated than the modifier. In contrast, relation priming is obtained only from the modifier prime and this finding is consistent with the CARIN theory (C. L. Gagne & E. J. Shoben, 1997) but inconsistent with schema-based theories of conceptual combination (e.g., G. L. Murphy, 1988; E. J. Wisniewski, 1996). PMID- 11204101 TI - Testing two theories of conceptual combination: alignment versus diagnosticity in the comprehension and production of combined concepts. AB - People often interpret novel noun-noun combinations by transferring a property from one constituent concept of the combination to the other. Two theories make different predictions about these "property" interpretations. Dual-process theory predicts that properties transferred will be alignable differences of the concepts being combined. Constraint theory predicts that properties transferred will be diagnostic properties of the concepts in which they originate. An experimental study tested these contrasting predictions in interpretation comprehension and interpretation production tasks. The results showed that participants reliably preferred diagnostic property interpretations, whether alignable or nonalignable, in both tasks. There was no reliable preference for alignable interpretations in either task. This confirms constraint theory's predictions about property interpretations and goes against the predictions of dual-process theory. PMID- 11204102 TI - On the necessity of alignment: reply to Costello and Keane (2001). AB - In their article, "Testing two theories of conceptual combination: Alignment versus diagnosticity in the comprehension and production of combined concepts," F. J. Costello and M. T. Keane (2001) evaluate the role of alignment in the interpretation of noun-noun combinations. They found that participants were not strongly biased to prefer and produce interpretations with alignable differences. Instead, participants sometimes preferred and produced interpretations with nonalignable differences. These results are surprising given that most research has found advantages of alignable differences over nonalignable differences. Costello and Keane also found that feature diagnosticity better predicted their results, and they concluded that alignment does not play an important role in conceptual combination. However, drawing on recent work, the author of the present article gives an alternative interpretation of Costello and Keane's results, showing that alignment is crucial in conceptual combination. The author also shows that the dual-process model accounts for their results. PMID- 11204103 TI - Entropy and variability discrimination. AB - Two experiments examined college students' discrimination of complex visual displays that involved different degrees of variability or "entropy." Displays depicted 16 black and white line drawings of various types (e.g., a brain, a clock, a hand); the participants were required to classify a display in terms of its variability (e.g., a low-variability display contains many identical items, whereas a high-variability display contains few identical items). The participants' accuracy and reaction time scores on a 2-alternative forced-choice discrimination disclosed that people can and do use entropy to classify different levels of visual display variability. Individuals differed in their use of absolute rather than relative entropy. PMID- 11204104 TI - Representational momentum and Michotte's (1946/1963) "launching effect" paradigm. AB - In A. Michotte's (1946/1963) launching effect, a moving launcher contacts a stationary target, and then the launcher becomes stationary and the target begins to move. In this experiment, observers viewed modifications of a launching effect display, and displacement in memory for the location of targets was measured. Forward displacement of targets in launching effect displays was decreased relative to that of targets (a) that were presented in isolation and either moved at a constant fast or slow velocity or decelerated or (b) that moved in a direction orthogonal to previous motion of the launcher. Possible explanations involving a deceleration of motion or landmark attraction effects were ruled out. Displacement patterns were consistent with naive impetus theory and the hypothesis that observers believed impetus from the launcher was imparted to the target and then dissipated. PMID- 11204105 TI - The discrepancy-attribution hypothesis: I. The heuristic basis of feelings of familiarity. AB - B. W. A. Whittlesea and L. D. Williams (1998, 2000) proposed the discrepancy attribution hypothesis to explain the source of feelings of familiarity. By that hypothesis, people chronically evaluate the coherence of their processing. When the quality of processing is perceived as being discrepant from that which could be expected, people engage in an attributional process; the feeling of familiarity occurs when perceived discrepancy is attributed to prior experience. In the present article, the authors provide convergent evidence for that hypothesis and show that it can also explain feelings of familiarity for nonlinguistic stimuli. They demonstrate that the perception of discrepancy is not automatic but instead depends critically on the attitude that people adopt toward their processing, given the task and context. The connection between the discrepancy-attribution hypothesis and the "revelation effect" is also explored (e.g., D. L. Westerman & R. L. Greene, 1996). PMID- 11204106 TI - The combined contributions of the cue-familiarity and accessibility heuristics to feelings of knowing. AB - A model for the basis of feeling of knowing (FOK) is proposed, which combines 2 apparently competing accounts, cue familiarity (L. M. Reder, 1987), and accessibility (A. Koriat, 1993). Both cue familiarity and accessibility are assumed to contribute asynchronously to FOK, but whereas the effects of familiarity occur early, those of accessibility occur later and only when cue familiarity is sufficiently high to drive the interrogation of memory for potential answers. General information questions were used to orthogonally manipulate cue familiarity and accessibility. As expected, both familiarity and accessibility enhanced FOK judgments, but the effects of accessibility were found mostly when familiarity was high. This interactive pattern was replicated when FOK judgments were delayed but not when they were immediate. The results support the proposed cascaded model of FOK but also imply a differentiation between 2 variants of the accessibility heuristic. PMID- 11204107 TI - von Restorff revisited: isolation, generation, and memory for order. AB - The effects of isolation and generation on memory for order were investigated in 4 experiments. Experiments 1 and 2 examined the effect of isolation on order retention. Previous investigations in this area have yielded equivocal results. Experiments 1 and 2 revealed that isolation enhances memory for order: Isolated items were repositioned more accurately than comparable items in control lists. Experiments 3 and 4 investigated the effect of generation on order retention. These experiments revealed that generation can enhance, disrupt, or have no effect on memory for order, depending on the relative number of generated items appearing within a list. Implications of these results for general theoretical accounts of isolation effects in memory are discussed. A simplified version of the feature model (J. S. Nairne, 1990) is shown to provide a general account of isolation effects. PMID- 11204108 TI - Using temporal information to construct, update, and retrieve situation models of narratives. AB - Four experiments explored how readers use temporal information to construct and update situation models and retrieve them from memory. In Experiment 1, readers spontaneously constructed temporal and spatial situation models of single sentences. In Experiment 2, temporal inconsistencies caused problems in updating situation models similar to those observed previously for other dimensions of situation models. In Experiment 3, merely implied temporal order information was inferred from narratives, affecting comprehension of later sentences like explicitly stated order information. Moreover, inconsistent temporal order information prevented the creation and storage in memory of an integrated situation model. In Experiment 4, a temporal inconsistency increased processing time even if readers were unable to report the inconsistency. These results confirm the significance of the temporal dimension of situation models. PMID- 11204109 TI - Selecting one among many referents in spatial situation models. AB - Five experiments related anaphor resolution to a classic memory variable, namely, interference created by multiple uses of a given object-concept, and by spatial distance of the referent from the reader's focus of attention. Participants memorized a diagram of a building with rooms containing objects, and then read narratives describing characters' activities there. Reading was self-paced word by word. Accessibility was measured by readers' time to understand anaphoric sentences containing a definite noun phrase referring to an object in its room. Spatial distance between the object and the current focus of attention increased reading times for names of the object, the room, and sentence wrap-up. Multiple examples of a target-object increased its reading time only if they were scattered across different rooms. An associative model of memory retrieval during text comprehension was used to interpret the complex pattern of results. PMID- 11204110 TI - Proper-name processing: are proper names pure referencing expressions? AB - Theoretical models of proper-name processing have been primarily derived from studies of people's names; however, they are thought to generalize to all classes of proper name. Five experiments are reported that use repetition priming to compare different classes of proper names. It was found that for people's names and landmark names, (a) production of a name in response to seeing a picture primed a subsequent familiarity decision to the same item's written name and (b) similarly, making a familiarity decision to an auditory presentation of a name primed a familiarity decision to the same item's written name. No comparable facilitation was found for the country-name stimuli. The presence of this specific facilitation was attributed to the nature of connectivity between conceptual and lexical representations. Theoretical views that proper names are unique, meaningless labels and that they are pure referencing expressions are evaluated. PMID- 11204111 TI - Estimation of electron absorbed fractions in the extrathoracic airways. AB - Dose calculations using the respiratory tract model presented in Publication 66 of the International Commission on Radiological Protection (ICRP) frequently predict that the basal cells of the anterior portion of the nose, the extrathoracic region ET1 of the model, are the most highly irradiated tissue of the body. The dose to the basal cells is averaged over a layer of tissue 10 microm thick located at a depth of 40 microm into the airway. Reported here are the results of a series of absorbed fraction calculations undertaken to compare with values tabulated in ICRP Publication 66. The Monte Carlo code MCNP4B and the geometric model of the ET1 region specified in Publication 66 were used in the calculations. Although some calculated differences are evident between the two sets of absorbed fractions, typically less than 20%, the calculations confirm that the electron absorbed fractions tabulated in Publication 66 are not responsible for the high estimates of the ET1 dose. PMID- 11204112 TI - The measurement of radiation levels in Australian zircon milling plants. AB - The processing of zircon often involves grinding it to a fine powder known as zircon flour. As the resulting particles are small they may be inhaled if they become airborne and, since they contain some uranium and thorium, deliver radiation doses to workers. Theoretical estimates and measured radiation exposure in Australian zircon milling plants are reported in this paper. Theoretical doses, calculated in this work, indicate a potential maximum dose to workers of 5.5 mSv y(-1). Measured doses, based on normal work practices, vary in different plants from 0.66 mSv to 1.03 mSv y(-1) and suggest that in the dustiest Australian zircon milling plants the maximum dose would be of the order of 1 mSv y(-1). Measurements, which focused on the dustiest operations, indicate an upper limit of dose of about 3 mSv y(-1). Based on the theoretical and measured doses not exceeding 6 mSv y(-1), workers would not be designated as Category A workers, and probably would not be designated Category B workers, exceeding 1 mSv y(-1), under the guidelines of a EURATOM Directive. PMID- 11204113 TI - Natural radioactivity in the soil samples of Coastal Karnataka of South India. AB - Studies on radiation level and radionuclide distribution in the region of Coastal Karnataka, India, were undertaken. The purpose of this study is to provide baseline data on radiation level and radionuclide distribution in the region for the future assessment of the impact of the nuclear and thermal power stations that are being set up in the region. Further, this study may reveal information on the transportation of radionuclides in the environment. The external gamma dose rates in air have been measured throughout Coastal Karnataka using a sensitive plastic scintillometer. The measured dose rates include both terrestrial and cosmic ray components. The gamma dose rates in air range from 26 to 174 nGy h(-1) with a median value of 74 nGy h(-1). The activities of naturally occurring radionuclides in the soil samples of the region were measured using HPGe gamma ray spectrometry, and the resulting doses in air were calculated. The activity of 40K varies from 61.0 to 316.7 Bq kg(-1) with a median of 117.5 Bq kg( 1); the activity of 226Ra varies from 20.1 to 62.3 Bq kg(-1) with a median value 35.0 Bq kg(-1) and that of 232Th from 14.3 to 48.6 Bq kg(-1) with a median value of 29.8 Bq kg(-1). The mean absorbed dose rate in air due to naturally occurring radionuclides is found to be 41.5 nGy h(-1). In addition to this, the correlations between 226Ra and 40K, 232Th and 40K, and 226Ra and 232Th were computed from the results of the concentration of these naturally occurring radionuclides. A weak correlation was observed between 226Ra and 40K and between 232Th and 40K while a moderately good correlation was observed between 226Ra and 232Th. The results of these systematic investigations are presented and discussed in this paper. PMID- 11204114 TI - A dosimetric model for determining the effectiveness of soil covers for phosphogypsum waste piles. AB - Phosphogypsum (PG) is a by-product of the phosphoric acid production process that contains high concentrations of U-series radionuclides. PG piles formed during the last 30 years cover about 1,200 hectares and are located close to the town of Huelva (Spain) on a salt-marsh. The regional government of Andalusia restored the area beginning in 1990 by covering it with a 25-cm-thick layer of natural soil. With this restoration, the external gamma-dose rate in the zone has decreased drastically, approaching near environmental background values. This conclusion is based on results obtained through in-situ monitoring measurements and through a dosimetric model developed for that particular radiation source. As the model uses average parameters of the studied site, its output does not show a correlation point by point with the in-situ monitoring measurements. However, a good agreement is observed in average values over the covered piles. The model gives an average dose rate of 0.41 mGy y(-1) and the in situ monitoring 0.40 mGy y(-1). Based on this model, it is possible to calculate the necessary thickness of soil to reduce the dosimetric contribution from a similar extension of PG until the desired level is reached. In our conditions, in a 25-cm-thick soil, about 0.19 mGy y(-1) is the increase produced by the PG layer in relation to an infinitum soil layer. Consequently, no radiological concern exists in the restored zones with respect to the external gamma radiation. PMID- 11204115 TI - Depth dose-equivalent and effective energies of photoneutrons generated by 6-18 MV X-ray beams for radiotherapy. AB - Photoneutron production was investigated on Siemens KD 2 and Varian Clinac accelerators operating in the 6-18 MV range. Neutron dose equivalent rates were measured on the surface of a water phantom at the isocenter of the accelerators and also inside the phantom at depths of 1, 5, and 10 cm and off-axis distances of 0, 20, and 50 cm. Superheated drop detectors based on dichlorofluoromethane and etched-track detectors with boronated converters were employed in this study. The energy response of these detectors permits a direct measurement of dose equivalent without prior knowledge of the neutron energy spectra. Dose equivalent rates were assessed using the Q(L) relationship from ICRP publication 60, as well as using earlier data from ICRP publication 21. This permitted both a comparison with previously published data and an assessment of the impact of the recent ICRP recommendations--which were found to increase the dose equivalent levels by about 30%. In addition, the depth corresponding to 50% of maximum dose equivalent, dH50, was determined along the central axis of the beams and at 50 cm off-axis. Monte Carlo neutron transport calculations were performed to determine the depth dose equivalent distributions in a phantom irradiated with monoenergetic neutrons. Effective energies of the photoneutron spectra were then estimated by comparing our measured dH50 values to those calculated for monoenergetic neutrons. It was found that the effective photoneutron energy is 1.8-2.1 MeV within the 10-18 MV x-ray beams, and it is 0.5-0.8 MeV for photoneutrons transmitted through the accelerator head. Data from this work cover most of the x ray beam energies in clinical use and permit an assessment of integral dose values as well as specific organ doses to a radiotherapy patient. PMID- 11204116 TI - Epithelial damage thresholds for multiple-pulse exposures to 80 ns pulses of CO2 laser radiation. AB - Corneal epithelial damage thresholds for exposures to 80 ns pulses of 10.6 microm infrared radiation produced by a CO2-TEA laser were investigated. Thresholds were determined for sequences of 1, 2, 8, 32, 128, and 1,024 pulses at pulse repetition frequencies of 10 and 16 Hz. Threshold damage is correlated by an empirical power law of the form EDth = CN(-alpha) in which EDth, is the threshold radiant exposure per pulse, and N is the number of pulses. The constants C and alpha are similar for the two pulse repetition frequencies. For the combined data set, C = 2,955 J m(-2) pulse(-1) (295.5 mJ cm(-2) pulse(-1) and alpha = 0.178. This value of the constant C is within 5% of the measured damage threshold for a single 80 ns pulse exposure. Temperature calculations reveal that the maximum temperature increase on the beam axis, 10 microm beneath the anterior tear surface, resulting from the different threshold exposures is constant to within +/-10% of the mean values. This result is consistent with a critical temperature damage model. Damage threshold measurements on cooled corneas indicate that the damage mechanism indeed has a substantial thermal component. PMID- 11204118 TI - Evaluation of scatter contribution from shielding materials used in scatter measurements for calibration range characterization. AB - The contribution of scatter from the shielding material used in scatter measurements at the Ohio Emergency Management Agency was evaluated. This was accomplished by comparing physical measurements with results generated by detectors modeled in the Monte Carlo shielding code, MCNP4B. The high purity germanium (HPGe) detector model was improved by using radiographs to more accurately represent the detector geometry, including a model of the lithium contact transition region, and considering the effects of the non-uniform electric field in the germanium crystal. Photons scattered from the shielding material were found to contribute 4.25% of the total scatter recorded by the HPGe detector (thus contributing only 0.26% of the total dose) at a point 5 m from a 1.35 GBq (36.4 mCi) 137Cs source. PMID- 11204117 TI - Monitoring methods and dose assessment for internal exposures involving mixed fission and activation products containing actinides. AB - Internal dose assessment for intakes of radionuclide mixtures is a difficult task. When the radionuclide mixture contains both the easy to detect gamma emitters, e.g., 60Co and 95Zr, and difficult to detect alpha emitters such as 239Pu and 241Am, a single monitoring method, such as in-vivo counting, is inadequate for detection and dose assessment. Recent experience with task related monitoring for such radionuclide mixtures at Ontario Power Generation CANDU nuclear power plants has offered an opportunity to review this topic and suggest a strategy for monitoring that involves a combination of in-vivo and in-vitro methods. Using the radionuclide composition data in a mixture from an actual case as an example, this paper describes a monitoring strategy for mixed fission and activation products, including the advantages and pitfalls of reliance on surrogate radionuclides for signaling the presence of actinides in the mixture. The described monitoring strategy is consistent with the recommendations of ICRP Publication 78, which advocates a "combination of techniques so as to make the best possible evaluation of an unusual situation, for example, a programme of both body activity and excreta measurements." The use of experience and professional judgement for interpreting the combined in-vivo and in-vitro data for interim and ultimate intake and dose assessment is discussed and emphasized. PMID- 11204119 TI - Absorbed dose to the adult male and female brain from 18F-fluorodeoxyglucose. AB - The absorbed doses to adult male and female brains from 18F-fluorodeoxyglucose were investigated. A total of eight male and six female patients undergoing clinical positron tomography brain scans were included in this study. This patient population allowed for a comparison of the absorbed dose to the brain in men and women. For each patient, time-activity curves for the brain were generated, yielding cumulated activity measurements for the entire organ. From these cumulated activities the average residence times for both male and female subjects were calculated and then multiplied by the S-values from the MIRDOSE 3.1 software program for absorbed dose estimates. The average absorbed dose per administered activity to the adult male brain was found to be 4.2 x 10(-2) mGy MBq(-1), which is lower than that found for the adult female brain of 5.3 x 10( 2) mGy MBq(-1). Six of the male and all six female subjects were each studied on two separate occasions, allowing for an analysis of within-subject variability. The average variation in the self-dose for all 12 patients was found to be within 14%, suggesting that in most cases this method of obtaining a single dose estimate is precise. PMID- 11204120 TI - Radiological findings of accidental radiation injury of the fingers: a case report. AB - This case report describes the medical follow-up of a 46-y-old (at the time of exposure) man who in 1971 accidentally exposed the fingers of his right hand to gamma-ray radiation from an iridium source that was used for nondestructive testing [estimated radiation dose: 26 Gy to 90 Gy (2,600 rad to 9,000 rad)]. No prominent acute injury was detected except for leukocytopenia (800 mm(-3)) and thrombocytopenia (15,000 mm(-3)). Three years later, the first, second, and third fingers presented repeated infection and started to develop contracture. Twenty two years after exposure, he underwent amputation of the first and second fingers, and a toe graft was done. Radiological examinations prior to and following the operation revealed atrophic change of the finger bones and arterial injuries. Angiographic findings coincided with the region and extent of radiation injury of the fingers, which indicates that arterial damage is involved in the development of this chronic disorder. PMID- 11204121 TI - Individual biodosimetry at the natural radiation background level. AB - The present note describes new advancements to a valued tool in retrospective biodosimetry that lower the threshold of detection of radiation dose to 29 mGy. The advanced method is based on the electron paramagnetic resonance measurements of stable radiation-induced radicals in tooth enamel. Earlier this method had been used only for reconstruction of high radiation doses obtained accidentally. New opportunity of reconstruction of doses lower than 100 mGy opens a new realm of possibilities for assessing the health effects of ionizing radiation at the natural radiation background level. PMID- 11204122 TI - Chest wall thickness measurements and the dosimetric implications for male workers in the uranium industry. AB - The Human Monitoring Laboratory has measured the chest wall thickness and adipose mass fraction of a group of workers at a Canadian uranium refinery, a conversion plant, and a fuel fabrication site using ultrasound. A site-specific biometric equation has been developed for these workers, who seem to be somewhat larger than other workers reported in the literature. Chest wall thickness is a very important modifier on lung counting efficiency and these data have been put into the perspective of the impending Canadian dose limits that will reduce the limit of occupationally exposed workers to 100 mSv in a 5-y period with a maximum of 50 mSv in any one year. The sensitivity of the germanium and phoswich based lung counting systems have been compared. Over a range of chest wall thickness of 1.6 cm to 6.0 cm and using a 30-min counting time, the achievable MDA's lie in the range of 6.7 mg to 19.1 mg or 6.7 mg to 30 mg with a two-phoswich-detector array or a germanium lung counting system, respectively. Depending on chest wall thickness, these achievable MDA's are close to, or exceed, the predicted amounts of natural uranium that will remain in the lung (absorption type M and S) after an intake equivalent to the Annual Limit on Intake that corresponds to 20 mSv. Neither system is sufficiently sensitive to detect an intake of Type S natural uranium in a worker with a chest wall thickness that corresponds to the average (3.73 cm) if it occurred more than 7 d prior to the lung count. PMID- 11204123 TI - Radiation from medical procedures: corrections to a consequential book review. PMID- 11204124 TI - Specific activity concept. PMID- 11204125 TI - The evolution of Candida species and fluconazole susceptibility among oral and vaginal isolates recovered from human immunodeficiency virus (HIV)-seropositive and at-risk HIV-seronegative women. AB - Antifungal agents can effectively treat mucosal candidiasis; however, their use can lead to colonization with less susceptible species and to resistance among normally susceptible strains. Oral and vaginal Candida isolates obtained at 3 points over 2 years from human immunodeficiency virus (HIV)-seropositive and at risk HIV-seronegative women were identified by species and were evaluated for in vitro fluconazole susceptibility. Prevalence of non-C. albicans strains increased over time, and these strains were more likely among women reporting current antifungal use. Among C. albicans isolates, resistance was rare, with no evidence for progressive reduction in susceptibility over time. Among non-C. albicans isolates, reduced susceptibility occurred frequently and increased with time. HIV seropositive women were more likely to have non-C. albicans isolates with reduced susceptibility as were women reporting current antifungal use. This evolution and section of mucosa-colonizing Candida species with reduced susceptibility could play a critical early role in the development of antifungal resistance among C. albicans isolates responsible for refractory candidiasis. PMID- 11204126 TI - Virus neutralizing antibodies against a panel of 18 BVDV isolates in calves vaccinated with Rispoval RS-BVD. AB - Seven of nine colostrum-deprived calves, free from infection with bovine virus diarrhoea virus (BVDV), were vaccinated with Rispoval RS-BVD on two occasions, 21 days apart, while the other two were kept as BVDV infection controls. The virus neutralizing (VN) serum antibodies induced by vaccination were tested for their ability to neutralize 18 European BVDV isolates, including laboratory reference strains and recent field isolates, both cytopathic and non-cytopathic biotypes as well as genotypes I and II. The strains were isolated in Belgium, France, Germany and the United Kingdom. While there were large variations in the vaccine-induced VN titres of the individual calves against all the strains, e.g. the titres against Osloss NCP, the European reference strain ranged from 1.7 to 6.7 (1:log2), serum from each animal was capable of neutralizing between nine and all 18 of the strains tested. Nevertheless, from the results of this study, it can be concluded that in colostrum-deprived BVDV seronegative calves, Rispoval RS-BVD can stimulate the production of VN antibodies capable of neutralizing a wide range of antigenically diverse European isolates of BVDV, including genotypes I and II. PMID- 11204127 TI - Relationship between the amounts of antibodies to Actinobacillus pleuropneumoniae serotype 2 detected in blood serum and in fluids collected from muscles of pigs. AB - An indirect ELISA method, previously used to detect antibodies to Actinobacillus pleuropneumoniae serotype 2 in serum of pigs, was further developed aiming to measure antibodies to the microbe in muscle fluids. Serum and muscle fluid were collected from Specific Pathogen Free (SPF) pigs as well as from SPF pigs challenged with A. pleuropneumoniae which were either treated with effective antibiotics or left as infected controls. The antibody responses measured in serum correlated well to the clinical signs of respiratory disease observed and to pathological lesions found at necropsy performed 17 days post-infection. The amounts of antibodies monitored in serum and in muscle fluid collected from the diaphragm and the thigh, respectively, were compared. Higher concentrations of antibodies were assessed in serum than in diaphragm fluid, which in turn contained more antibodies per ml than fluid collected from the thigh. The amount of antibodies to A. pleuropneumoniae measured in fluid from the diaphragm diluted 1/50 correlated well with the quantity measured in serum diluted 1/1000 (r2 = 0.87; P < 0.001). When validated by using serum antibody responses as a standard, the specificity of the ELISA employed in fluid from the diaphragm was found to be 100%. The sensitivity was determined to be 88% when calculated on seropositive pigs (A450 = 0.3 in serum diluted 1/1000). That figure increased to 97% if calculated on pigs expressing pronounced amounts of serum antibodies (A450 > or = 0.5). PMID- 11204128 TI - Epidemiology of ovine Campylobacter infection determined by numerical analysis of electrophoretic protein profiles. AB - The relationship of 50 Campylobacter strains isolated from aborted ovine foetuses, and the faeces of sheep, cattle and chickens were determined by numerical analysis of electrophoretic (SDS-PAGE) protein profiles. Comparison of protein patterns by numerical methods revealed differences between C. fetus ssp. fetus, C. jejuni, and C. coli strains as well as heterogeneity among isolates from different outbreaks. Isolates from each farm produced a distinct cluster and flocks from different locations were found to be infected with relatively different strains. In most cases, protein patterns of ovine foetal isolates were very similar to those of ovine faecal isolates. Ovine isolates of C. fetus ssp. fetus, C. jejuni and C. coli gave similar protein patterns to the corresponding Campylobacter species isolated from cattle or chicken, on the same farm. Thus, it was concluded that certain protein types of ovine Campylobacter strains were more likely associated with local areas, and Campylobacter strains causing ovine abortions are distributed in the environment more widely than assumed to date. PMID- 11204129 TI - Effect of long-term oral administration of an immunostimulant diet on innate immunity in sea bass (Dicentrarchus labrax). AB - Immunostimulants represent a modern and promising tool in aquaculture, enhancing the resistance of cultured fish to disease and stress. This study investigated the effect of a combination of dietary glucans, alpha-tocopherol and ascorbic acid on the innate immune response of cultured sea bass (Dicentrarchus labrax). After 5 weeks of adaptation on a commercial diet containing 100 p.p.m. ascorbic acid and 200 p.p.m. alpha-tocopherol, sea bass were switched to a diet supplemented with 2% beta-1.3/beta-1.6 glucans and ascorbic acid and alpha tocopherol at 500 p.p.m. The supplemented diet was given at 2% of body weight per day over a 2-week period, every 3 months. Plasma lysozyme concentration, content and distribution of major plasma proteins and complement activity were measured prior to feeding the supplemented diet and after 40 weeks. Alternative pathways of complement activation and lysozyme activity were both significantly enhanced in fish fed on glucans and elevated doses of vitamins. No significant differences were observed in protein content or in albumin/globulin ratio. Compared to lysozyme activity, which showed marked individual variation, complement-mediated haemolytic activity has been shown to be a more reliable indicator of sea bass immunocompetence. Further studies are in progress to clarify the effect of each dietary component on the innate immune response and disease resistance. PMID- 11204130 TI - A study of the ability of a TK-negative and gI/gE-negative pseudorabies virus (PRV) mutant inoculated by different routes to protect pigs against PRV infection. AB - The capacity of a TK-negative (TK-) and gI/gE-negative (gI/gE-) pseudorabies virus (PRV) mutant to protect pigs against Aujeszky's disease carried out by experimental infection with a virulent PRV strain, was tested. There were three groups, each of four susceptible pigs which were inoculated twice by two different schedules. Group 1 received the modified virus by the intradermal (first inoculation)-intramuscular (second inoculation) routes; group 2 was treated by the intranasal (first inoculation)-intramuscular (second inoculation) routes. The third group was left untreated as the control. All of the pigs were challenged intranasally with a virulent PRV strain and they were subsequently injected with dexamethasone. Two pigs in each group were necropsied on days 5 and 15 after dexamethasone inoculation. The challenge exposure resulted in mild clinical signs, increase in growth and a shorter period of virus shedding in vaccinated pigs, whereas the control group showed severe signs of Aujeszky's disease. No difference in the titre of the virulent virus which was excreted by pigs of all three groups, was observed and all animals seroconverted. Both the mutant strain and the wild-type virus established a latent infection although only the latter was reactivated and shed. Slight lesions were observed in target tissues of the vaccinated animals and no significant differences were detected between the two inoculation schedules. PMID- 11204131 TI - Histopathological and immunohistochemical study of lambs experimentally infected with Fasciola hepatica and Schistosoma bovis. AB - The aim of this study was to investigate the cross-resistance between Fasciola hepatica and Schistosoma bovis in lambs assessing parasitologic, gross pathologic, histopathologic and immunohistochemical changes in liver and small intestine. Thirty Castellana breed lambs were divided into five comparable groups and exposed to F. hepatical S. bovis (group F/S), S. bovis/F. hepatica (group S/F), S. bovis (group S) or F. hepatica (group F) and six unexposed lambs were used as non-infected controls (group C). Primary patent infection with F. hepatica induced a lower number of schistosome eggs and a higher number of lymphocytes in intestinal and liver schistosome egg-induced granulomas in group F/S than in the groups S/F and S, liver damage being mainly attributed to F. hepatica. S. bovis infection followed by challenge with F. hepatica particularly increased the severity of the most significant liver alterations (cholangiohepatitis by F. hepatica and mesoendophlebitis by S. bovis) and F. hepatica seemed not to have an influence on established S. bovis infection. In addition, immunohistochemical results suggested that the predominant local immune response in both double-infected groups was different, being mainly a cell mediated immune response in group F/S and a mucosal response in group S/F. PMID- 11204132 TI - Apoptosis in feline panleukopenia and canine parvovirus enteritis. AB - Tissue samples of cats and dogs with panleukopenia and parvovirus enteritis, respectively, were examined for the presence of viral antigen-positive cells and apoptotic cells by immunohistochemistry and by TUNEL assay (Terminal Transferase Mediated dUTP Nick End Labelling). Compared to control animals, infected cats and dogs generally had more TUNEL-positive cells. Cell types positive for parvovirus antigen, for example digestive tract epithelial and mesenchymal cells, and lymphocytes and macrophages in lymphoid tissues were also positive for TUNEL signals. Occasionally, TUNEL signal and viral antigen were present in the same tissue areas, suggesting a direct viral trigger of apoptosis. More frequently, however, there was no complete overlap of antigen and TUNEL-positive areas. The results of this study indicate that apoptotic cell death contributes significantly to the widespread tissue damage of parvovirus infection in cats and dogs. PMID- 11204133 TI - Clostridium botulinum and bio-compost. A contribution to the analysis of potential health hazards caused by bio-waste recycling. AB - Bio-waste recycling and the production and use of bio-compost are politically encouraged in Europe. Quality control takes no consideration of pathogenic anaerobic spore formers, e.g. Clostridium botulinum. A protocol for health hazard analysis concerning this pathogen has been developed. Samples of marketed bio compost were tested and results showed that about 50% of the tested samples contained C. botulinum. For the first time it has been shown that the use of bio compost represents a health hazard to humans and animals, especially in the future when spores will have accumulated in the environment. The use of household bio-waste collected in 'bio-bins' is apparently one factor involved in the production of contaminated compost end-products. Environmental factors in the propagation of C. botulinum are discussed. The improvement of bio-waste recycling technology and management should be encouraged in order to minimize the health hazard caused by contaminated bio-compost. PMID- 11204134 TI - A serological survey on erysipelas in chickens by growth agglutination test. AB - From March to April 1992, 200 culled chickens sent to an abattoir in Tokyo, Japan were examined for the presence of growth agglutinating antibody in the serum. In the serological survey, 11 (5.5%) of 200 chicken sera had high growth agglutination titres against Erysipelothrix rhusiopathiae, ranging from 1:16 to 1:128. These findings indicate a high rate of erysipelas infection among chickens in the field. PMID- 11204135 TI - Studies on oral health in mentally retarded adults. AB - During the last decades, a new policy involving normalisation, integration, equality and deinstitutionalisation of mentally retarded (MR) individuals has been accepted in Sweden. Consequently, many institutions have been closed and an increased number of people with MR are now integrated into the Swedish community. The general aim of this thesis was to investigate if a greater degree of independence for MR adults influenced the prevalence of oral diseases. MATERIAL AND METHODS: The caries incidence and prevalence, number of remaining teeth, incidence of tooth mortality and interproximal bone loss were investigated in a group of MR adults, aged 21-40 years, all with protracted, regular preventive dental care. The studied variables were related to living arrangements and degree of MR, and were followed during 8.5 years (Papers I, II and VI). Incidence and reasons for tooth mortality were studied during 10 years in institutionalised MR individuals (Paper III). In connection with the closing-down of an institution for MR adults, the changes of oral hygiene habits, sucrose intake and oral microbiological flora were studied in the new integrated living (Papers IV and V). RESULTS: Less restrictive living arrangements and mild forms of MR were correlated to a high caries prevalence in persons with MR. After 8.5 years, the caries incidence had decreased in all subjects, but persons with mild MR and those who lived integrated still had a higher caries prevalence than other MR adults. With the exception of subjects with Down syndrome, the interproximal bone loss during 8.5 years was similar or lower compared to normal Swedish populations. Institutionalised MR subjects had lost an average of 3.72 teeth during 10 years. Periodontitis was the main reason for tooth mortality. Persons who cooperated well with dental treatment and those who used neuroleptics lost fewer teeth during the 10-year period compared to other MR individuals. The proportion of subjects with high levels of mutans streptococci and subjects who showed growth of P. intermedia/P. nigrescens decreased after deinstitutionalisation, and less subjects consumed sucrose frequently. The oral hygiene routines, and the levels of lactobacilli, P. gingivalis and A. actinomycetemcomitans were not influenced by the change in living arrangements. A simplified saliva sampling method, involving licking directly on the bacteria culture, was developed to count lactobacilli in saliva when delivering whole saliva was impossible. CONCLUSIONS: Less restrictive living and a mild degree of MR were correlated to a high caries prevalence. Subjects with poor ability to cooperate with dental treatment and those with Down syndrome have an obvious risk of deteriorated oral health. However, compared to normal Swedish populations, the MR subjects studied in this thesis had, after several years of regular dental care, satisfactory oral health. PMID- 11204136 TI - From magic to science: a journey throughout Latin American medical mycology. AB - The start of Latin America's love story with fungi may be placed in pre-Hispanic times when the use of fungi in both ritual ceremonies and daily life were common to the native civilizations. But the medical mycology discipline in Latin America started at the end of the 19th Century. At that time, scholars such as A. Posadas, R. Seeber, A. Lutz and P. Almeida, discovered agents of fungal diseases, the study of which has influenced the regional research ever since. Heirs to them are the researchers that today thrive in regional Universities and Research Institutes. Two current initiatives improve cooperation among Latin American medical mycologists. First, the periodical organization of International Paracoccidioidomycosis Meetings (seven so far, from 1979 to 1999); second, the creation of the Latin American Association for Mycology in 1991 (three Congresses, from 1993 to 1999). Latin American publications have increased in international specialized journals such as that from our Society (ISHAM) (from 8% in 1967 to 19% in 1999), and the Iberoamerican Journal of Mycology (Revista Iberoamericana de Micologia; > 40% from 1997 to 1999). In addition, Latin American participation at ISHAM International Congresses has risen from 6.9% in 1975 to 21.3% in 1997, and 43.2% at the 14th ISHAM Congress, held for the first time in a Latin American country, Argentina. A significant contribution of women to the scientific establishment of Latin American medical mycology (e.g., 45% of Latin American papers vs. 18% of other regions published in Journal of Medical and Veterinary Mycology in 1987, had women as authors or coauthors) suggests a better academic consideration of Latin American women against their counterparts in the developed world. Taken together, all these figures reflect the enthusiasm of our Latin American colleagues in the field, despite the difficulties that afflict our region, and affect our work. PMID- 11204137 TI - Pathogenesis II: fungal responses to host responses: interaction of host cells with fungi. AB - Most of our knowledge concerning the virulence determinants of pathogenic fungi comes from the infected host, mainly from animal models and more recently from in vitro studies with cell cultures. The fungi usually present intra- and/or extracellular host-parasite interfaces, with the parasitism phenomenon dependent on complementary surface molecules. Among living organisms, this has been characterized as a cohabitation event, where the fungus is able to recognize specific host tissues acting as an attractant, creating stable conditions for its survival. Several fungi pathogenic for humans and animals have evolved special strategies to deliver elements to their cellular targets that may be relevant to their pathogenicity. Most of these pathogens express surface factors that mediate binding to host cells either directly or indirectly, in the latter case binding to host adhesion components such as extracellular matrix (ECM) proteins, which act as 'interlinking' molecules. The entry of the pathogen into the host cell is initiated by fungal adherence to the cell surface, which generates an uptake signal that may induce its cytoplasmic internalization. Once this is accomplished, some fungi are able to alter the host cytoskeletal architecture, as manifested by a rearrangement of microtubule and microfilament proteins, and this can also induce epithelial host cells to become apoptotic. It is possible that fungal pathogens induce modulation of different host cell pathways in order to evade host defences and to foster their own proliferation. For a number of pathogens, the ability to bind ECM glycoproteins, the capability of internalization and the induction of apoptosis are considered important factors in virulence. Furthermore, specific recognition between fungal parasites and their host cell targets may be mediated by the interaction of carbohydrate binding proteins, e.g., lectins on the surface of one type of cell, probably a parasite, that combine with complementary sugars on the surface of host-cell. These interactions supply precise models to study putative adhesins and receptor containing molecules in the context of the fungus-host interface. The recognition of the host molecules by fungi such as Aspergillus fumigatus, Paracoccidioides brasiliensis and Histoplasma capsulatum, and their molecular mechanisms of adhesion and invasion, are reviewed in this paper. PMID- 11204139 TI - Conventional versus molecular diagnostic tests. AB - In this session, emphasis was placed on the diagnosis of various mycoses through the identification of antibodies and antigens in sera, as well as on new techniques to properly identify medically important fungi through molecular biological procedures. The use of restriction fragment length polymorphism (RFLP) on fungal mitochondrial DNA (mtDNA) has enabled the identification of different strains of Sporothrix schenkii, several dermatophytes, Candida spp. and black fungi according to their species-specific mtDNA-RFLP patterns. In some species, distinct specific types where found in relation to the geographic origin of the patients. These particular molecular diagnostic tests are useful in the identification of strains and in epidemiological studies. An account of the applications of serological methods in the diagnosis of paracoccidioidomycosis was presented. Serology has been used in the identification of paracoccidioidomycosis using a specific, sensitive and rapid antibody-based immunodiagnosis method. Using the gp43 antigen, the diagnostic coverage of inmunodifussion has been improved from the 93-95% achieved with crude antigens, to 100% in an enzyme-linked immunodiffusion assay capture test. Cross-reactions were eliminated by treatment of the antigen with sodium metaperiodate. Antibody detection is useful, especially in paracoccidioidomycosis and histoplasmosis. PMID- 11204138 TI - Candida albicans: adherence, signaling and virulence. AB - The focus of this symposium was to present new information on the morphogenesis of Candida albicans, particularly how it relates to signal transduction pathways and other genes involved in the regulation of morphogenesis. In addition, we discuss the role of adherence and colonization of the oral cavity by the organism and discuss the role of mannan as an adhesin that recognizes the human red blood cell. C. albicans utilizes at least two signal pathways to regulate its conversion from a yeast form to filamentous growth (hyphae). One of these two pathways is similar to the Saccharomyces cerevisiae pseudohyphal/mating pathway, which utilizes the regulatory protein, Cphlp. The other pathway is not totally defined but requires a second regulatory protein, referred to as Efg1p. Other signal pathways may exist, which include a two-component histidine kinase and response regulator proteins. The latter pathway(s) may include proteins such as Chk1p, Ssk1p, Shi1p and Cos1p/Nik1p. Mutations in strains, which specifically target these proteins, result in morphogenesis defects and avirulence or attenuation of strains. A growth regulatory gene has also been recently defined whose expression is associated with growth cessation and which appears to be a necessary prerequisite in conversion of the organism to a filamentous growth form. Starvation of yeast cells induces exponentially grown cells (and usually non-germinative) to germinate. This phenomenon is also observed in cells that are transiently treated with metabolic inhibitors. During each of these treatments (starvation, metabolic inhibition), expression of a growth regulatory gene (CGRI) increases. Adherence of C. albicans to host cells and tissues is complex; several proteins, which appear to have host recognition functions, have been defined. In the oral cavity, C. albicans selectively adheres to salivary proteins, which are absorbed to many oral surfaces. This mechanism enables the cells to colonize surfaces of the oral cavity. An understanding of these interactions may lead to strategies to prevent oral disease. Mannan from C. albicans may provide a host recognition function for C. albicans. Recent experiments indicate that mannan binds to human red blood cells and causes hemolysis. Binding of mannan to the band 3 protein of human red blood cells has been established. This activity may be associated with the ability of the organism to utilize hemoglobin (and iron). PMID- 11204140 TI - Non-culture based diagnostic tests for mycotic infections. AB - Non-culture methods being developed and evaluated for mycotic infections include polymerase chain reaction (PCR), galactomannan (GM) antigenemia, Western blot (WB) to detect antibodies, and detection of the fungal metabolites D-arabinitol and (1,3)-beta-D-glucan. Sample preparation for PCR from blood specimens depends on fractionation of peripheral blood, its pre-incubation in blood culture broth, or a total DNA method, which does not rely on fractionation, or pre-incubation. Targets for PCR of fungi in the 18S or ITS2 subunits of the ribosomal RNA genes facilitated the design of Aspergillus and Candida genus and species probes. Amplicons were identified using PCR-enzyme linked immunosorbent assay (ELISA) or reverse line-blot formats. A pilot study indicated that PCR tests on blood specimens were positive at least once in patients with confirmed invasive aspergillosis (IA). When serum-PCR and serum-GM tests were compared in IA patients, antigenemia was more often positive. PCR detected Aspergillus DNA in bronchoalveolar lavage specimens from patients at risk even when cultures were negative. D-Arabinitol can be detected as a marker of candidiasis with gas chromatography-mass spectrometry or enzyme dependent-fluorometry. Each method can differentiate the microbial D- and host L-enantiomers. (1,3)-beta-D-Glucan is produced by most genera of pathogenic fungi and can be detected in plasma by the 'G-test'. In patients with febrile neutropenia the efficacy of azole therapy correlated with plasma (1,3)-beta-D-glucan concentrations of > or = 10 pg ml(-1). The diagnosis of early acute pulmonary histoplasmosis can be improved by a WB test utilizing deglycosylated M antigen, a 94-kDa glycoprotein. The identity of M antigen as a catalase was deduced from the sequence of the cloned gene. PCR identification of Histoplasma capsulatum cultures was accomplished with primer pairs selected from H and M antigen gene sequences. PMID- 11204141 TI - Clinical applications of non-culture based methods for the diagnosis and management of opportunistic and endemic mycoses. AB - Nonculture based methods for the detection of infections caused by fungal pathogens are becoming more important tools in the management of infected patients. Detection of fungal antigens and DNA appear to be the most promising in this respect for both opportunistic and endemic mycoses. In this article we present an overview of the most recent developments in nonculture based methods and examine their value in clinical practice. PMID- 11204142 TI - Toxigenic fungi: which are important? AB - Growth of commonly occurring filamentous fungi in foods may result in production of mycotoxins, which can cause a variety of ill effects in humans, from allergic responses to immunosuppression and cancer. According to experts, five kinds of mycotoxins are important in human health around the world: aflatoxins, ochratoxin A, fumonisins, certain trichothecenes, and zearalenone. These toxins are produced by only a few species of fungi, in a limited range of commodities. Aflatoxins are potent carcinogens, produced by Aspergillus flavus and A. parasiticus in peanuts, maize and some other nuts and oilseeds. Ochratoxin A is a kidney toxin and probable carcinogen. It is produced by Penicillium verrucosum in cereal grains in cold climates, by A. carbonarius in grapes, wines and vine fruits, and by A. ochraceus sometimes in coffee beans. Fumonisins, which may cause oesophageal cancer, are formed by Fusarium moniliforme and F. proliferatum, but only in maize. Trichothecenes are highly immunosuppressive and zearalenone causes oestrogenic effects; both are produced by F. graminearum and related species. Current reporting probably underestimates the effect of mycotoxins as a cause of human mortality. PMID- 11204143 TI - Epidemiology: surveillance of fungal infections. AB - Surveillance for fungal diseases is essential to improve our understanding of their epidemiology and to enable research and prevention efforts to be prioritized. In order to conduct better surveillance for fungal diseases, it is important to develop more accurate and timely diagnostic tests, to follow rigorous epidemiological methods and to have adequate support from public health agencies and the pharmaceutical industry. Investigations of nosocomial and community outbreaks of fungal infection have also resulted in a better understanding of the sources and routes of transmission of these diseases, and of the risk factors for infection. This has led to more effective prevention and control strategies. In addition, outbreak investigations have offered excellent opportunities to develop new molecular sub-typing methods, and to evaluate and validate older ones. For example, results obtained from a global epidemiological study of the genomic structure of Cryptococcus neoformans have led to a better understanding of the epidemiology of cryptococcosis. Similarly, a study of variations in the genotype of Trichophyton rubrum has found that patients may become infected with multiple strains, which has important implications for study design when looking at the epidemiology of dermatophyte infections. PMID- 11204144 TI - Epidemiology of tinea capitis. AB - This paper addresses the changing epidemiology of tinea capitis in the USA and in Europe that has occurred over the last several decades. Several dermatophytes are involved in the etiology, and the primary etiological agents of tinea capitis are limited to the genera Microsporum and Trichophyton. In addition, the sources of these infections are discussed and although geophilic dermatophytes occur worldwide, anthropophilic species and some zoophilic fungi may be geographically restricted, depending on host range. For example, tinea capitis due to geophilic organisms is rare in the USA. PMID- 11204145 TI - Molecular typing of pathogenic fungi. AB - In this Round Table, the application of several methods of molecular typing were discussed in reference to four important pathogenic fungi: Coccidioides immitis, Histoplasma capsulatum, Candida albicans and Paracoccidioides brasiliensis. Among the different methods the following were discussed: restriction fragment length polymorphisms (RFLP), single nucleotide polymorphisms, random amplified polymorphic DNA (RAPD), polymerase chain reaction (PCR)-RFLP and microsatellites. By means of these methods, several important biological questions related to speciation, mode of reproduction and population genetics could be approached. The basic information obtained from this approach has implications in the understanding of these pathogenic fungi in relation to their behavior and the development of pathogenic features, such as resistance to antimicrobials and virulence factors used for colonization of mammalian hosts. The knowledge obtained from these studies could also be used for the development of innovative diagnostic methods, as well as for novel therapeutic approaches and production of vaccines. PMID- 11204146 TI - Deep Candida infections in the neutropenic and non-neutropenic host: an ISHAM symposium. AB - A symposium was held on May 8, 2000 to discuss the management of deep infections with Candida species. Among the findings discussed were the following. Candiduria is most often benign, though it occurs in patients with serious underlying diseases. Candida species are now the fourth most common cause of nosocomial bloodstream infections, usually arising from an intravenous catheter. Candida albicans represents only 50-60% of the isolates. There has been no change in the frequency of fluconazole resistance in C. albicans but some of the other species now being isolated from blood are constitutively more resistant to this drug. Nevertheless, for most non-neutropenic patients with candidemia, fluconazole is a reasonable choice for initial therapy. In the neutropenic patient, candidemia is now uncommon. Deep candida infections in neutropenic patients are usually being treated empirically with an amphotericin B formulation. Hepatosplenic candidiasis is usually detected only after recovery from neutropenia but can be suspected by imaging techniques. Improved diagnostic techniques for deep candidiasis in the neutropenic patient remain a critical requirement. PMID- 11204147 TI - Cryptococcosis: clinical and biological aspects. AB - The incidence of cryptococcosis rose dramatically with the advent of the acquired immune deficiency syndrome (AIDS) epidemic in the early 1980s until the early 1990s. The frequency of cryptococcosis has been declining since mid 1990s in Europe and America due to the development of more effective antiretroviral therapy and prophylactic treatment regimens designed to prevent fungal infections. The disease, however, is still recognized as one of the most common life-threatening opportunistic fungal infections in immunocompromised patients, particularly among those infected with human immunodeficiency virus (HIV). For this reason, research interest in clinical and biological aspects of the disease remains high. In addition to previously embarked areas of research, the cryptococcal research community has taken advantage of the current sequencing technology and initiated genome sequencing of Cryptococcus neoformans var. neoformans. This review includes various areas of research interest ranging from pathobiology, biochemistry and immunology, to genomics. PMID- 11204148 TI - Invasive aspergillosis. AB - Acute invasive aspergillosis (IA) is a devastating disease. Early diagnosis allowing an early treatment may improve the prognosis. However, this goal remains difficult to achieve. When diagnosis is confirmed it is often already too late. Galactomannan antigen detection and DNA detection are under clinical evaluation to improve early diagnosis and management of treatment. Despite antifungal treatment mortality rate is still high. Clinical resistance is more often due to the intensity of immunodepression than to high minimum inhibitory concentrations to antifungal agents; however, resistance to itraconazole may occur in rare instances. Beside acute IA, a chronic form of this infection may be seen as chronic necrotizing pulmonary aspergillosis or chronic invasive sinusitis. Other sites of infection have been described. The patients are immunocompetent or present minor alteration of their immunity or of anatomic structure of the infected site. Among patients with solid organ transplantation, lung and liver transplant patients are at the highest risk of developing IA. A high degree of awareness and efforts for an early diagnosis may participate to improve the poor prognosis. PMID- 11204149 TI - Emerging pathogens. AB - The ever increasing numbers of immunosuppressed individuals has led to a significant increase in the incidence of opportunistic infections, particularly those caused by fungi. The epidemiology of infections caused by the common fungal pathogens such as Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus has been well documented. However, in addition to these, a number of species which have previously been unrecognized (e.g., C. dubliniensis) or have previously been assumed to be non-pathogenic (e.g., Saccharomyces cerevisiae, Scedosporium spp. and Fusarium spp.) have emerged as agents of human disease. Since these species have only been identified recently as human pathogens, their role in disease is poorly understood. In most cases, identification of these species is problematic and therefore their epidemiology has yet to be elucidated adequately. In addition, several of these species fail to respond to conventional antifungal therapies. In this article, we describe the emergence of two separate yeast species (C. dubliniensis and S. cerevisiae) and two separate groups of moulds (Scedosporium prolificans and Fusarium spp.), as human pathogens. It is apparent from what we already know, that much work has yet to be performed before we have a clear understanding of how these species cause disease and most importantly how they can be controlled. PMID- 11204150 TI - Pneumocystis infections: the iceberg? AB - Pneumocystis carinii pneumonia (PCP) is a well-recognized lung disease of immunocompromised patients, but the real impact of Pneumocystis infection in humans remains to be discovered. Pneumocystis represents probably one of the more frequent infectious agents faced by humans. Seroconversion revealed P. carinii primary infection in > 90% of infants and small children, but the infection source and the clinical or pathological changes associated with this first contact with the parasite remain unknown. Pneumocystis organisms are atypical microfungi able to attach specifically to type-I alveolar epithelial cells, and to proliferate, provoking severe pneumonitis. A deep impairment of cell-mediated immunity associated with changes in pulmonary surfactant make it possible for Pneumocystis to grow within the host. Alveolar type-II cell hypertrophy, macrophagic infiltrate and intra-alveolar foamy eosinophilic material are the most typical changes. CD4+ T-lymphocytes and interferon play a major role in host defense against P. carinii. Alveolar macrophages phagocytose P. carinii via the macrophage-mannose receptor and produce reactive free-radicals and nitric oxide under Pneumocystis stimulation. Furthermore, PCP is associated with an early decrease of surfactant phospholipids, increased hydrophilic surfactant protein (SP) levels and decreased hydrophobic SPs. Normal surfactant improves PCP, and consistently, it inhibits the parasite growth. New detection tools have revealed that hospitalized patients can be latently infected with Pneumocystis and that immunocompetent hosts develop transient Pneumocystis infections. Pneumocystis organisms circulate in human populations, being able to infect hosts with diverse susceptibility levels. In fact, airborne Pneumocystis infection can display a large spectrum of clinical presentations and most likely, we recognize at present only the tip of the iceberg. PMID- 11204151 TI - New aspects of some endemic mycoses. AB - The treatment of mycetomas varies according to their etiological agents and the clinical state of the patient. For the treatment of eumycetomas, the azole derivatives are the drugs of choice, with itraconazole rendering better results than ketoconazole and presenting better tolerance. Actinomycetomas are treated according to different therapeutic schemes: dapsone plus sulfamethoxazol trimethoprim (SMT), and streptomycin or amikacin or amoxicillin plus clavulanic acid. The first therapeutic scheme is very useful in the treatment of Nocardia mycetoma, while the association of amikacin plus SMT is the best treatment for those cases produced by Actinomadura madurae. Ciprofloxacin is a very useful drug for the treatment of actinomycotic mycetomas with bone lesions. Although there are several criteria for evaluating clinical outcome there is no accepted criterion of cure. During the 1990s, there was a remarkable increase in the incidence of coccidioidomycosis in California, USA. An almost ten-fold increase in the number of cases was registered during 1992 and 1993 over the usual incidence. A gradual reduction in coccidioidomycosis cases was observed in the late 1990s. This particular coccidioidomycosis outbreak took place in areas of low endemicity, as well as in those of usual high endemicity. Among the factors believed to have influenced this phenomenon were a drought followed by abundant winter/spring rainfall, increased immigration of susceptible individuals, increase in excavation/construction work and a better diagnosis of the infection, particularly in the last part of the decade. The majority of patients presented the usual clinical manifestations of symptomatic primary infection but an unusual number of cases with acute respiratory failure were observed. PMID- 11204152 TI - Black fungi: clinical and pathogenic approaches. AB - Data are presented on the clinically relevant black yeasts and their relatives, i.e., members of the Ascomycete order Chaetothyriales. In order to understand the pathology of these fungi it is essential to know their natural ecological niche. From a relatively low degree of molecular variability of the black yeast Exophiala dermatitidis, potential agent of brain infections in patients from East Asia, it is concluded that this species is an emerging pathogen, currently going through a process of active speciation. It is found to be an oligotrophic fungus in hot, moist environments, such as steambaths. Cladophialophora-, Fonsecaea- and Ramichloridium-like strains, known in humans as agents of chromoblastomycosis, are frequently found on rotten plant material, but the fungal molecular diversity in the environment is much higher than that on the human patient, so that it is difficult to trace the etiological agents of the disease with precision. This approach has been successful with Cladophialophora carrionii, of which cells resembling muriform cells, the tissue form of chromoblastomycosis, were found to occur in drying spines of cacti. Phagocytosis assays provide a method to distinguish between pathogens and non-pathogens, as the killing rates of strict saprobes proved to be consistently higher than of those species frequently known as agents of disease. The therapeutic possibilities for patients with chromoblastomycosis are reviewed. PMID- 11204153 TI - Mycoses in the transplanted patient. AB - The incidence of invasive fungal infection (IFI) has increased considerably over the past 20 years, and transplant recipients are at especially high risk for fungal infections owing to their overall immunosuppressed condition. Organ transplantation procedures were incorporated as a therapeutic option for many patients who lacked the normal functions of organs such as the heart, liver, kidney, lung, pancreas and small bowel. The prevalence of IFI in solid organ transplant (SOTR) patients ranges from 5 to 50% in kidney and liver transplants, respectively. In bone marrow transplant (BMT) patients, IFI are major causes of morbidity and mortality due to the protracted neutropenic period and graft-versus host disease. Candida spp. and Aspergillus spp. account for >80% of fungal episodes in both SOTR and BMT. The development of new immunosuppressive agents, new prophylaxis strategies (as pre-emptive therapy) and the improvement in surgical techniques led to increase survival of transplant recipients. In this session, a clear and concise update of the recent advances in the laboratory diagnosis of candidiasis and aspergillosis in this kind of patients was presented. However, we still need to establish more rapid, sensitive and specific methods for IFI diagnosis. Representatives of the 'Subcomision de Infecciones en el Paciente Neutropenico y Transplantado (SIPNYT)' de la Sociedad Argentina de Infectologia (SADI), presented the results of an unusual multicenter study both retrospective and descriptive studies of IFI in SOTR and BMT patients in Argentina. In addition, a study of IFI in 1,861 SOTR patients from four centers and the analysis of IFI in 2,066 BMT patients from all 12 BMT centers from Argentina was presented. From these studies it can be concluded that 'all transplant recipients are not the same' and that they should be stratified according to their different risk degrees in order to determine the best prophylaxis and treatment strategies. PMID- 11204154 TI - Mycoses in AIDS. AB - Major changes are occurring in the epidemiology of opportunistic infections (OI) in patients with acquired immune deficiency syndrome (AIDS) and treated with highly active antiretroviral therapy (HAART). A marked decrease of minor and major OI was observed and clinical resistance of thrush to antifungal agents became extremely rare. Primary and secondary prophylaxis against Pneumocystis carinii infections can be stopped; however, the situation is less clear for other OI such as cryptococcosis or endemic mycoses. The epidemiology is dramatically different in the countries which cannot afford the cost of HAART for the majority of patients, such as South Africa. These topics will be discussed in this paper. PMID- 11204155 TI - Mycoses associated with AIDS in the Third World. AB - Despite advances in diagnosis and treatment, the epidemiological status of the human immunodeficiency virus (HIV) infection is far from under control in most of the developing world. Sub-Saharan Africa, Southeast Asia and India show increased rates of new infections. In Latin America and the Caribbean there were 1.6 million estimated cases of HIV-infected patients at the end of 1997. Fungal diseases have been one of the most relevant diagnoses in relation to the acquired immunodeficiency syndrome (AIDS). Infections due to Candida species and Cryptococcus neoformans var. neoformans are common worldwide. Histoplasma capsulatum, Coccidioides immitis and Penicillium marneffei are important causes of disease in endemic areas. Infection due to Sporothrix schenckii, Blastomyces dermatitidis and Paracoccidioides brasiliensis are uncommon even where they are endemic. Phaeohyphomycetes, hyalohyphomycetes and zygomycetes are still rare as a cause of disease among AIDS patients. However, agents pertaining to these groups, such as Aspergillus spp., have an increasing incidence. Superficial mycoses due to dermatophytes have special features from epidemiological, clinical and therapeutic points of view. PMID- 11204156 TI - The efficacy of acquired humoral and cellular immunity in the prevention and therapy of experimental fungal infections. AB - In the past two decades, numerous studies have documented the importance of acquired immunity for host defense against invasive fungal infections. There is widespread consensus in the field of medical mycology that cellular immunity is critical for successful host defense against fungi. However, in recent years several studies have established the potential efficacy of humoral immunity in host protection against two major fungal pathogens: Candida albicans and Cryptococcus neoformans. For C. albicans, antibodies to mannan, proteases and a heat shock proteins have been associated with protection against infection. Furthermore, anti-idiotypic antibodies to antibodies recognizing killer toxin from Pichia anomala and mimicking natural anti-killer toxin receptor antibodies can protect against C. albicans and other microorganisms. For C. neoformans, antibodies to the capsular glucuronoxylomannan have been shown to mediate protection in animal models of infection. Vaccines that induce protective antibodies have been shown to protect against experimental C. albicans and C. neoformans infection. In contrast, humoral immunity has not yet been demonstrated to mediate protection against Coccidioides immitis. For C. immitis, protection against infection is thought to rely on T cell mediated immunity, and the emphasis is on identifying the antigens that stimulate protective cellular immune responses and several candidate vaccines have been identified. These results provide encouragement for the view that acquired immune responses can be mobilized for the prevention and treatment of fungal infections. PMID- 11204157 TI - In vitro antifungal susceptibility methods and clinical implications of antifungal resistance. AB - As new antifungal agents are introduced for the treatment of infections caused by yeasts and filamentous fungi (moulds), it is important that reliable methods are available for the in vitro testing of both new and established agents. The ultimate goal of in vitro testing is the prediction of the clinical outcome of therapy. The use of the M27-A procedures that were developed by the US National Committee for Clinical Laboratory Standards (NCCLS) has led to increased interlaboratory agreement of minimum inhibitory concentrations (MICs) for yeasts and has facilitated the establishment of interpretive breakpoints for fluconazole and itraconazole. The clinical relevance and limitations of these breakpoints are discussed elsewhere. The focus of this paper is to review the advantages and disadvantages of the available methods for antifungal susceptibility testing of yeasts and moulds as well as the clinical implications of in vitro antifungal resistance. PMID- 11204158 TI - Combined treatment: antifungal drugs with antibodies, cytokines or drugs. AB - To improve present results with antifungal drugs, modulation of the host immune response is being explored. Human phagocytes of various lineages work cooperatively in vitro with antifungal drugs to inhibit or kill fungal pathogens, and this activity is augmented by several recombinant cytokines. Monoclonal antibodies against the cryptococcal capsule have been shown to act as an adjunct in enhancing the outcome of cryptococcosis in animal models. This approach is now being pursued in systematic clinical trials. In experimental candidiasis, several manipulations of the immune system, via administration of cytokines, gene deletion or antibodies to cytokines, have been shown to significantly affect survival and fungal clearance in vivo. This approach has already been demonstrated to be of benefit with recombinant human granulocyte-colony stimulating factor adjunct therapy of human candidiasis. Combining antifungal drugs of different classes may enhance their therapeutic effect. PMID- 11204159 TI - New advances in antifungal treatment. AB - Clinical aspects of treatment of invasive aspergillosis, infections caused by dematiaceous fungi, and mycoses caused by endemic, dimorphic fungi, are described in this review. PMID- 11204160 TI - Antifungal compounds: controversies, queries and conclusions. AB - A new session in this Congress was the development of a discussion panel regarding controversies and queries about the main topics of treatment and prophylaxis of severe systemic mycoses. Experts presenting each side of three controversial areas provided an interchange of ideas and clarified those areas where there remain substantial disagreements. Some common recommendations have been made, and some differences persist. The contents of this session are compiled in this paper. Due to the limitations of space, this paper presents the most relevant parts of each presentation. The large and up-to-date list of references should be useful to gain a better understanding of these subjects. PMID- 11204161 TI - Training medical myocologists in developing countries. AB - Although there has over recent years been a marked rise in the incidence of serious fungal infections, many of which are prevalent in developing countries, few facilities exist for diagnosis and research in medical mycology. In most countries, medical mycology is not taught adequately to medical students and consequently there is little awareness of the importance of fungal infections. Model teaching programmes need to be developed. Practical knowledge of mycoses, their diagnosis and treatment and also basic mycology can be disseminated through well-constructed courses and workshops. Formalized training in mycology research also needs to be introduced. To achieve all of this, expertise and additional resources need to be made available. In this regard, ISHAM can and should help. PMID- 11204162 TI - New targets and delivery systems for antifungal therapy. AB - Development of new approaches for treatment of invasive fungal infections encompasses new delivery systems for approved and investigational compounds, as well as exploiting the cell membrane, cell wall and virulence factors as putative antifungal targets. Novel delivery systems consisting of cyclodextrins, cochleates, nanoparticles/nanospheres and long circulating ('stealth') liposomes, substantially modulate the pharmacokinetics of existing compounds, and may also be useful to enhance the delivery of antifungal agents to sites of infection. Further insights into the structure-activity relationship of the antifungal triazoles that target the biosynthesis of ergosterol in the fungal cell membrane have led to the development of highly potent broad spectrum agents, including posaconazole, ravuconazole and voriconazole. Similarly, a novel generation of cell-wall active semisynthetic echinocandin 1,3 beta-glucan inhibitors (caspofungin, FK463, and VER-002) has entered clinical development. These agents have potent and broad-spectrum activity against Candida spp, and potentially useful activity against Aspergillus spp. and Pneumocystis carinii. The ongoing convergence of the fields of molecular pathogenesis, antifungal pharmacology and vaccine development will afford the opportunity to develop novel targets to complement the existing antifungal armamentarium. PMID- 11204163 TI - Mycotoxins and toxigenic fungi. AB - Mycotoxins and the fungi that produce them are of increasing importance as causes of human illness, but the diseases produced remain poorly understood at the clinical level. This paper explores four aspects: the increase of interest in ochratoxin A, factors affecting mycotoxin production, toxicology of the major mycotoxins, and the identification of Penicillium species which cause food spoilage and are important in indoor air. PMID- 11204164 TI - Prominent animal mycoses from various regions of the world. AB - The mycoses selected for presentation in this section are relatively common diseases of companion animals or livestock in certain areas of the world. Malasseziosis is arguably the most frequent mycosis of dogs (as otitis externa and dermatitis) throughout the world, although its diagnosis is often overlooked. Protothecosis is also geographically widespread, particularly in cattle where severe mastitis is a result of adventitious infection from the environment. In contrast, coccidioidomycosis and pythiosis are geographically limited in their occurrence (coccidioidomycosis by geographic region and pythiosis by climate), but within regions where they do occur, their presence in animals is not unusual. It was our intention to review recent developments in each of these diseases. PMID- 11204165 TI - Natural pathogens of laboratory animals and their effects on research. AB - The natural fungal pathogens of laboratory animals such as rabbits and guinea pigs are mainly dermatophyte species, most commonly Trichophyton mentagrophytes and also, less frequently Microsporum gypseum and M. canis. However, the incidences of infection and clinical disease are low in well-managed animal facilities. Young or immunocompromised rabbits are thought to be most susceptible. Dermatophytes infect the epidermis and adnexal structures, including hair follicles and shafts, usually on or around the head, and cause pruritus, patchy alopecia, erythema and crusting. Histopathological changes in the underlying skin occur and these changes could confound histological studies involving the skin. Yeast infections usually due to Candida spp. have been reported occasionally in laboratory animals. In this paper, the role of rodents in the evaluation of topical antifungal agents, dermatophytosis and two species of Candida, which are natural pathogens of laboratory animals, are discussed in relation to their effects on research. Pneumocystis carinii, an inhabitant of the respiratory tract of laboratory mice and rats, is a pathogen only under conditions of induced or inherent immunodeficiency. Infected mice and rats are likely to develop severe pneumocystosis following immunosuppression and will be rendered unsuitable for most experimental purposes. PMID- 11204166 TI - Clues to the presence of pathogenic fungi in certain environments. AB - The presence of various pathogenic fungi in rather unsuspected hosts and environments has always attracted the attention of the scientific community. Reports on the putative role of animals in fungal infections of humans bear important consequences on public health as well as on the understanding of fungal ecology. Fungi are ubiquitous in nature and their great capacity for adaptation allows them to survive and indeed, to thrive, in plants, trees and other natural substrata. Nonetheless, we are just beginning to learn the significance that these diverse fungal habitats have on the increasing number of immunosuppressed individuals. The accidental or permanent presence of fungi in animals, plants, soils and watercourses should not be taken too lightly because they constitute the source where potential pathogens will be contracted. If those fungal habitats that carry the largest risks of exposure could be defined, if seasonal variations in the production of infectious propagules could be determined, and if their mode of transmission were to be assessed, it would be possible to develop protective measures in order to avoid human infection. Additionally, unsuspected avenues for the exploration of fungal survival strategies would be opened, thus enhancing our capacity to react properly to their advancing limits. This paper explores several ecological connections between human pathogenic fungi and certain animals, trees, waterways and degraded organic materials. The occurrence of such connections in highly endemic areas will hopefully furnish more precise clues to fungal habitats and allow the design of control programs aimed at avoiding human infection. PMID- 11204167 TI - Fungal morphogenesis and virulence. AB - Phenotypic variability in pathogenic fungi has long been correlated with virulence, but specific genetic and molecular mechanisms are only recently being unraveled. Fungal morphogenesis, reflecting the expression of several regulated genes, and the capacity of the rising forms or phases to cause disease has been focused on at the XIVth Congress of the International Society for Human and Animal Mycology. Three experimental models of pathogenic fungi have been discussed. In Cryptococcus neoformans, phenotypic variability or switching represents controlled and programmed changes rather than random mutations. Evaluated phenotypic traits were the capsular polysaccharide, cell and colony morphology and virulence. In the dimorphic Paracoccidioides brasiliensis, the serine-thiol proteinase from the yeast phase cleaves the main components of the basal membrane, thus being potentially relevant in fungal dissemination. In Candida albicans, relationships between adhesion proteins and those of lymphocytes and neutrophils are related to fungal pathogenicity. Regulation of the directional growth of hyphae and its tropic responses are correlated with the invasive potential of C. albicans. PMID- 11204168 TI - Knockout mice as experimental models of virulence. AB - Infection models with animals whose immune systems have been selectively altered by neutralization of endogenous cytokines or by deletion of a gene have provided a valuable means to study the function of cells or cytokines in the context of complex multidimensional interactions. In particular, knockout mice have allowed a deeper insight into the in vivo performance of antifungal innate and acquired immunity, whose interplay is considered fundamental in the general defense against infections. It is conceivable that such an integrated view of effector and regulatory immune mechanisms operating in opportunistic fungal infections would facilitate the search for cells, cytokines and molecular pathways that are essential to control fungal infectivity or oppose fungus-associated immunopathology. PMID- 11204169 TI - The lipophilic yeasts: state of the art and prospects. AB - Malassezia yeasts (lipophilic yeasts), have been classified to include seven species. Although molecular methods such as sequencing of RNA and karyotyping were used to determine the species, traditional techniques are also being explored for their identification. These include studies of morphology and the utilization of individual lipids. Reports now show the predominance of individual species recovered from normal skin and from patients with diseases such as pityriasis versicolor and seborrhoeic dermatitis. The majority of systemic infections reported have been in the bloodstream of premature neonates. Clusters of cases have occurred and molecular techniques employed to study the epidemiology. With the development of discriminatory methods to determine individual species and strains present in disease and in nature, our understanding of the pathogenicity and the epidemiology of this genus can be advanced. PMID- 11204170 TI - Pathogenesis I: interactions of host cells and fungi. AB - The interactions of host cells and fungi during infection represent a complex interplay. Although T helper 1 (Th1)-mediated immunity is primarily responsible for acquired resistance to Paracoccidioides brasiliensis, studies have demonstrated that polymorphonuclear neutrophils play a critical role in providing an early resistance to this organism. One study has shown that the invasiveness of Candida albicans requires adherence, particularly to endothelial cells, which in turn are stimulated to express various cell-markers and pro-inflammatory cytokines as part of a proactive resistance to invasion. Somewhat in contrast to infection with C. albicans, it has been shown that the capsular glucuronoxylomannan of Cryptococcus neoformans causes the shedding of host-cell adherence molecules (L-selectins) needed for the migration of host-inflammatory cells to sites of infection and likely explains, in part, the reduced host inflammatory response to this organism. Resistance to aspergillosis is often associated with the immune status of the host. In one set of studies, it has been demonstrated that lymphocytes have little direct effect on the organism, but that antigen-presenting dendritic cells stimulate the production of Th1 cytokines, suggesting a positive role for the dendritic cell in host-response. Similarly, another study has shown that among the regulatory cytokine networks that Th2 associated cytokines (e.g., interleukin-10) likely play a detrimental role in the resistance of the host to Aspergillus fumigatus. PMID- 11204171 TI - Mechanical circulatory support systems--a review. AB - Congestive Heart Failure (CHF) is a major health problem with a high mortality rate. Its ultimate therapy, heart transplantation, is limited by the shortage of donor hearts. Since decades researchers have been working to solve this problem by developing Mechanical Circulatory Support Systems (MCSS) that can replace or assist the failing heart. Short-term and intermediate-term ventricular assist devices are used nowadays frequently to bridge patients with severe heart failure to recovery. Long-term ventricular assist devices (VADs) and Total Artificial Hearts (TAHs) are used increasingly as a bridge to heart transplantations or as permanent circulatory support in patients with end-stage heart failure that are contraindicated for heart transplantation. The early TAHs and VADs were mainly driven from an external pneumatic drive unit. The latest generation TAHs and long term assist devices are electrically powered, ultracompact, totally implantable, and have small wearable drive/control consoles, allowing patients to return to their daily activities. The article categorizes and reviews the development of MCSS, highlights the medical indications and contraindications of pump implantation, advantages and disadvantages of the various systems, and results of animal and clinical studies. PMID- 11204173 TI - Cost effectiveness analysis of BMD referral for DXA using ultrasound as a selective pre-screen in a group of women with low trauma Colles' fractures. AB - Measurements of bone density (BMD) are central to the World Health Organisation (WHO) approach to the definition of osteoporosis. Dual energy X- ray absorptiometry (DXA) remains the gold standard technique for measuring the bone mineral density (BMD) but Quantitative Ultrasound (QUS) is an attractive alternative method of bone assessment because it is easy to use and relatively inexpensive. It has been suggested that QUS could be used as a selective population pre-screen, to maximise the cost effectiveness of referral for DXA assessment of BMD. We set out to examine how such an approach might perform in the assessment of women with low trauma Colles' fracture. In 46 women aged 50-80 (mean 67) years we used DXA to measure BMD at lumbar spine and hip, and heel bone ultrasound to measure Broad Band Attenuation (BUA) and Velocity of Sound (VOS). We calculated local costs of pounds sterling 45 for DXA and pounds sterling 15 for QUS. We identified a BUA threshold of 60 dB/MHz as most cost effective as pre screen, and calculated a sensitivity of 93% and specificity of 84% in identifying those subjects who were subsequently identified as having osteoporosis by DXA. DXA assessment of all patients had a cost of pounds sterling 77 per osteoporotic subject identified. We examined the cost-effectiveness of using QUS as a pre screen, only referring subjects for more expensive DXA assessment if BUA was less than 60 dB/MHz. However this approach had no advantage, still costing pounds sterling 78 per osteoporotic subject identified. QUS assessment does not appear cost-effective as a pre-screen for DXA, even in this high risk group of women with low trauma Colles' fracture. A QUS pre-screen would only be cost-effective if the scan could be performed at a substantially lower cost. PMID- 11204172 TI - Phenotypical characterization of c-kit receptor deficient mouse femora using non destructive high-resolution imaging techniques and biomechanical testing. AB - OBJECTIVE: Pathological processes in bone can lead to fatal health consequences. Therefore, it is important to study factors that possibly influence the activity of bone cells. The mast cell is a normal component of bone, storing and producing many potent bioactive substances. One of the most important factors to influence mast cell number, function, and phenotype is the c-kit ligand. A defect of the c kit receptor leads to mast cell deficiency. In literature oversight, evidence for the importance of mast cells in skeletal homeostasis is compiled. METHODS: To investigate the influence of c-kit receptor deficiency on bone mass, geometry, microstructure, and strength, 30 femora of profoundly c-kit receptor deficient mouse mutants and 30 control group animals aged 8-20 weeks were phenotypically characterized using peripheral quantitative computed tomography (pQCT), micro computed tomography (microCT) and 3-point-bending. RESULTS: The femora of the c kit receptor and therefore mast cell deficient animals were significantly altered in bone mass and geometry but not in bone density and microstructure. The mutants had a lighter femur with a thinner shape. The lower load bearing capacity of the femora of mast cell deficient mouse mutants is more likely explained by the smaller amount of bone material than due to a change in intrinsic material properties. TECHNICAL CONSIDERATIONS: With the little dimensions of mouse bones, it is of prime importance to have precise methods to phenotypically characterize the bone. The pQCT allows the separate assessment and analysis of trabecular and cortical bone density, as well as a statement about bone geometry. Beyond it, the microCT-technique delivers a 3-D analysis of bone microstructure, which so far was only achieved with 2-D histomorphometry. microCT is an efficient alternative to destructive histological preparations allowing further biomechanical testing of the same specimens to also deliver measures for bone strength. PMID- 11204174 TI - Arousal norms for children age 5-16 years based on home polysomnography. AB - Fragmentation of sleep by brief arousals has become an acknowledged aspect of poor quality sleep but there is a shortage of normative data on such arousals, especially for children. Norms for arousals (defined according to American Sleep Disorders Association criteria) were compiled for 61 children age 5-16 years using the Oxford Medilog system for a single night of home polysomnography. No significant differences were seen between the five age subgroups considered in average number of arousals per hour of sleep although individual differences were apparent at each age level and arousal duration was somewhat longer at younger ages. The low arousal rates in the children studied are in keeping with other evidence that arousal rates increase throughout life. Boys were no different from girls in either arousal frequency or duration. Arousal frequency was correlated with PSG awakenings but only to a modest extent. These new normative values should be useful in clinical practice and research for the assessment of the quality of children's sleep. PMID- 11204175 TI - Content-based retrieval of breast cancer biopsy slides. AB - The Biopsy Analysis Support System (BASS), previously used for image analysis of immunohistochemically stained sections of breast carcinoma, has been extended to include indexing and content-based retrieval of biopsy slide images from a database of 57 captured cases. Images from histopathological biopsy slides are described and these are accessed in terms of the properties of either individual nuclei or groups of cell nuclei present in the slide. Visual similarity of cases is specified in terms of a diagnostic index, commonly known as the H-score, which incorporates the heterogeneity of nuclear staining intensity, as well as the percentage of nuclei staining at specific intensities. The system provides a platform that can be exploited in telepathology and teleconsultation, but further research is needed to explore its full potential and accuracy in a diagnostic clinical environment. PMID- 11204176 TI - Reengineering the biomedical-equipment procurement process through an integrated management information system. AB - The design of each new hospital site is typically preceded by decisions on the most appropriate level of biomedical equipment which significantly influences the layout of the hospital departments which are under construction. The most appropriate biomedical equipment should ideally be decided upon considering a series of demographic and social parameters of the hospital and international regulations and standards. This information should ultimately be distilled to proper technical specifications. This paper proposes a streamlined management process related to the procurement of biomedical equipment for new hospital sites or for those under expansion. The new management process aims to increase the efficiency of the experts involved in the definition of the most appropriate level of equipment and its technical specifications. It also addresses all aspects of the biomedical equipment-selection cycle, including the evaluation of the bids submitted by the equipment suppliers. The proposed process is assisted by a management information system, which integrates all related data-handling operations. It provides extensive decision-support facilities to the expert and a platform for the support of knowledge re-use in the field of biomedical-equipment selection. PMID- 11204177 TI - Differentiation in murine mastocytoma induced by macrophage gangliosides. AB - In the membrane of mouse macrophages two gangliosides were detected which inhibit the division of murine mastocytoma P815 tumor cells. The two gangliosides were incorporated into the cytoplasmatic membrane of mastocytoma cells. The concentration necessary to achieve a complete inhibition of P815 tumor cell division is about 1 microM for both effective gangliosides. Macrophage ganglioside-induced inhibition of cell division is accompanied by morphological changes of the mastocytoma cells. While the cells are rounding, their diameter increases and serotonin and granules appear in the cytoplasm of the enlarged cells. Our findings suggest that macrophage gangliosides may differentiate mastocytoma cells into mast cells. PMID- 11204178 TI - Flight and molecular modeling study on the response of codling moth, Cydia pomonella (Lepidoptera: Tortricidae) to (E,E)-8,10-dodecadien-1-ol and its geometrical isomers. AB - In a previous study we have reported that both (E,Z)-8,10-dodecadienol (E,Z) and (Z,Z)-8,10-dodecadienol (Z,Z) isomers inhibit the attraction of male codling moth, Cydia pomonella L. when added to (E,E)-8,10-dodecadienol (E,E) while the (Z,E)-8,10-dodecadienol (Z,E) isomer induces slight increase in the number of males attracted to the pheromone source. In the present study, we have tested the behavioral activity of the individual geometrical isomers E,Z; Z,E and Z,Z. A few number of codling moth males flew to the Z,E-isomer while the other two isomers (i.e. E,Z and Z,Z) did not elicit any upwind orientation. Analysis of the flight behavior to the E,E- and Z,E-isomer showed significant differences in most of the flight parameters evaluated. Based on the biological observations and molecular modeling, we suggest that the behavioral activity of the Z,E-isomer is due to presence of specific receptors for this isomer on male antennae and not to its structural resemblance to the E,E-isomer. These results underline the importance of the Z,E-isomer in sex attraction of male codling moth. PMID- 11204179 TI - Phenolic constituents from the lichen Parmotrema stuppeum (Nyl.) Hale and their antioxidant activity. AB - Lichen, Parmotrema stuppeum (P. stuppeum) was successively extracted with benzene and acetone. Both the extracts were fractionated on 1% oxalic acid impregnated silica gel column to obtain four phenolic compounds. The structures of compounds were identified by 1H and 13C NMR spectra as methyl orsenillate, orsenillic acid, atranorin and lecanoric acid respectively. Antioxidant activity of benzene extract, acetone extract and isolated compounds were evaluated in a beta-carotene linoleate model system. The pure compounds showed moderate antioxidant activity. This is the first report on the isolation and characterisation of compounds from the lichen P. stuppeum as well as on their antioxidant activity. PMID- 11204180 TI - Iseluxine: a novel isoquinolinone alkaloid from Iseia luxurians. AB - A novel isoquinolinone alkaloid, iseluxine (1), has been isolated from the epigeal parts of Iseia luxurians (MORIC.) O'DONELL (Convolvulaceae), a climber indigenous to the tropical Americas. Structural elucidation was achieved by HRMS, 1H NMR, 13C NMR, and HMBC spectroscopy. N- and/or O-methyl derivatives of 1 are already known from certain Magnoliidae families, e.g., the Fumariaceae, the Lauraceae, or the Papaveraceae. Iseluxine, the "missing link" in the biosynthesis of these methyl derivatives from dopamine, is the first isoquinolinone alkaloid characterized by a catechol substructure. PMID- 11204181 TI - Furanoheliangolides from leaves of Neurolaena macrocephala. AB - Six sesquiterpene lactones, two new (3 and 6) and four known (1, 2, 4 and 5) were isolated from the leaves of the Mexican Neurolaena macrocephala (Asteraceae). The furanoheliangolide 6, containing 4beta,5-dihydro-9alpha-hydroxy-atripliciolide as basic structure, was found for the first time in nature. The chemotaxonomic importance of this phytochemical work is discussed. PMID- 11204182 TI - Antibacterial activity of Citrus reticulata peel extracts. AB - Citrus peels were successively extracted with hexane, chloroform and acetone using a soxhlet extractor. The hexane and chloroform extracts were fractionated into alcohol-soluble and alcohol-insoluble fractions. These fractions were tested against different gram positive and gram negative bacteria. The EtOH-soluble fraction was found to be most effective. Fractionation of EtOH-soluble fraction on silica gel column yielded three polymethoxylated flavones, namely desmethylnobiletin, nobiletin and tangeretin. Their structures were confirmed by UV, 1H, 13C NMR and mass spectral studies. The findings indicated a potential of these natural compounds as biopreservatives in food applications. PMID- 11204183 TI - Seasonal variations in the harpagoside content of Scrophularia scorodonia L. AB - Seasonal variations on the content of harpagoside in Scrophularia scorodonia L. (Scrophulariaceae) were investigated using plants collected monthly from January to December in 1995. During growth of this species the percentage of harpagoside was the highest during the maximum development of the plant, specially in July. Harpagoside levels differed among leaves, stems and flowers of S. scorodonia. Leaves were distinguished from other plant parts by higher levels of harpagoside. Drying at ambient temperature influenced the yield of harpagoside compared with the results of plant drying by microwave. PMID- 11204184 TI - Probing stimulants from the rice plant towards the smaller brown planthopper, Laodelphax striatellus (FALLEN) (Homoptera: Delphacidae). AB - When adult males of the smaller brown planthopper, Laodelphax striatellus were fed on 2% crude rice (leaf and stem) extract containing 15% sucrose there were characteristic stylet sheaths deposited on parafilm membrane. Further bioassays with the butanol-soluble fr. of the extract revealed that it is highly effective for the insects. When the butanol fr. was charged on an ODS open column and eluted in sequence with 20, 40 and 100% methanol in water, the ODS-40% methanol fr. was shown as the most effective one. Further separation of the ODS-40% methanol fr. resulted in six effective components. These components acted to stimulate very high probing response on L. striatellus only when they are combined. This activity was found to be similar to those of the ODS-40% methanol fr. and the original crude rice plant extract. Two of the active components were identified as tricin 5-O-glucoside and tricin 7-O-glucoside, respectively, through spectroscopic analyses. PMID- 11204185 TI - A pyoverdin from Pseudomonas sp. CFML 95-275. AB - From Pseudomonas sp. CFML 95-275 a pyoverdin was isolated with a cyclopeptidic substructure. It could be shown that this pyoverdin is identical with one obtained from Pseudomonas fluorescens BTP 7 for which a lactone structure had been deduced from the interpretation of a FAB spectrum. The elucidation of the correct structure of the pyoverdin is described. PMID- 11204186 TI - The cooccurrence of different biflavonoid types in Pilotrichella flexilis. AB - From Pilotrichella flexilis various flavonoids have been isolated. This species contains in contrast to P. cuspidata not only 3',3'''-binaringenin and related compounds, but also some hitherto unknown biflavonoids based on eriodictyol and aureusidin. The structures of two new compounds are elucidated spectroscopically. Possible causes for the differences of the flavonoid patterns between the two species of the genus Pilotrichella are discussed. PMID- 11204187 TI - Triflavones and a biflavone from the moss Rhizogonium distichum. AB - From gametophytes of Rhizogonium distichum have been isolated the biflavone dicranolomin and five triluteolins. Two of the triluteolins, which were named rhizogoniumtriluteolin and distichumtriluteolin, were new compounds; their structures have been elucidated spectroscopically. PMID- 11204188 TI - Megistolactone, a new alkaloid from Sarcomelicope megistophylla. AB - A new quinolone alkaloid, megistolactone (1) was isolated from the bark of Sarcomelicope megistophylla. Its structure has been elucidated on the basis of MS and NMR data. From a biogenetic point of view, this compound should be considered as an oxidation product of 1,2,3,4-tetra-O-subsituted acridone alkaloids, which are also present in the bark. PMID- 11204189 TI - Polyphenolic compounds from Plantago lagopus L. AB - In the present study we report the isolation of a phenylpropanoid glucoside, plantamajoside, together with rosmarinic acid, chlorogenic acid and luteolin-7-O monoglucoside. This is the first report of these compounds from Plantago lagopus. PMID- 11204190 TI - Alkylresorcinols in fruit pulp and leaves of Ginkgo biloba L. AB - These studies were undertaken to characterise resorcinolic lipids (5-n alk(en)ylresorcinols) composition and to determine their seasonal fluctuations in fruit pulp and leaves of Ginkgo biloba L. Resorcinolic lipid concentrations were consistently higher in fruit pulp than in leaves. In pulp, several mono- and di unsaturated homologs of alkylresorcinols were the predominant group of analysed lipids. Contrary to the fruit pulp, only 5-n-pentadecylresorcinol was demonstrated in leaves. Initially, the alkylresorcinol's content both in pulp and leaves increased until June-July and decreased following seeds ripening. This trend continued until senescence of leaves in late September and October. PMID- 11204191 TI - Antimicrobial activities of Ferulago essential oils. AB - Essential oils from Ferulago asparagifolia Boiss., F. galbanifera (Miller) W. Koch, F. humilis Boiss. (Endemic), F. trachycarpa Boiss. growing in Turkey were evaluated against 15 microorganisms for their antifungal and antibacterial activity using an agar tube dilution and microdilution broth susceptibility assay, respectively. The essential oil compositions were investigated by GC/MS. Inhibitory effects against Escherichia coli, Enterobacter aerogenes, Candida albicans, Gaeumannomyces graminis var. tritici, Sclerotium rolfsii and Fusarium moniliforme were remarkable. Results are discussed in comparison with the chemical composition of the essential oils. PMID- 11204193 TI - Two new flavonol glycosides as DNA topoisomerase I poisons. AB - Flavonoids are secondary plant metabolites whose anticancer properties are actually being studied from an epidemiological and pharmacological point of view. They are believed to be implicated in the lower risk of some forms of cancer observed in Asian countries, due to their capacity to control cell proliferation, to act on certain regulatory enzymes as protein kinases or topoisomerases. Based on these precedents, three flavonols isolated from a cytotoxic butanol extract from Retama sphaerocarpa Boissier have been assessed to study their topoisomerase I and II activity. Two new rhamnazin glycosides were found to have the ability to stabilize the cleavage complex human DNA topoisomerase I at concentrations in the 100-250 microM range, acting as topoisomersase I poisons. PMID- 11204192 TI - Degradation of anthracene by bacteria isolated from oil polluted tropical soils. AB - Four bacteria, identified as Pseudomonas aeruginosa, Alcaligenes eutrophus, Bacillus subtilis and Micrococcus luteus were isolated from crude oil polluted soils using anthracene as the sole carbon and energy source. All the organisms utilized n-hexadecane, n-tetradecane, diesel oil, engine oil and naphthalene as sole carbon sources. None could utilize hexane, cycloheptane, xylene, benzene, toluene, phenol, fluoranthene,and kerosene as carbon sources. Highest cell density obtained with 0.1% (w/v) anthracene were 4.5 x 10(7) (cfu/ml), 8.6 x 10(6) (cfu/ml), 5.4 x 10(6) and 2.4 x 10(6) (cfu/ml) respectively, for P. aeruginosa, A. eutrophus, B. subtilis and M. luteus after 30 days incubation. Growth of the organisms on a Nigerian crude oil resulted in a residual oil concentration of 22.2%, 33.3%, 39.3%, 44% and 91.7% respectively, for P. aeruginosa, A. eutrophus, B. subtilis, M. luteus and the noninoculated control on the 14 th day. Ring fission enzymes of the meta pathway were detected in induced cells of P. aeruginosa and A. eutrophus while ortho pathway enzymes were detected in B. subtilis and M. luteus. P. aeruginosa and A. eutrophus had specific catechol-2,3-dioxygenase activities of 3.8 +/- 0.183 and 0.64 +/- 0.032 micromol/min x mg protein respectively while catechol-1,2-dioxygenase activities of 1.95 +/- 0.029 and 1.89 +/- 0.026 micromol/min x mg protein were detected in B. subtilis and M. luteus respectively. This work, highlights the capability of these unreported tropical strains of A. eutrophus, B. subtilis and M. luteus as anthracene degraders. PMID- 11204194 TI - Fatty acid oxidizing activity in a red marine alga, Porphyra sp. AB - A crude enzyme solution prepared from fronds of Porphyra sp. showed remarkable oxygen uptake activity when linoleic acid was added as a substrate. Fatty acid oxidizing activity was mainly present in the soluble fraction of the crude homogenate. The activity was purified 769-fold from mature fronds by ammonium sulfate fractionation, ion-exchange and hydrophobic chromatography. SDS-PAGE analysis of the purified proteins indicated that its subunit size was about 13 kDa. Gel filtration chromatography equipped with a photodiode array detector revealed that the activity was associated with a protein having a molecular weight of 12,500-13,000. It eluted with a chromophore having the maximum absorbance at 417 nm, thus, the protein was suggested to be a heme protein. The spectrophotometric property of the protein was highly similar to that of cytochrome c suggesting that it has heme c as a prosthetic group. The protein showed highest oxygenation activity against linoleic acid, and alpha-linolenic acid and arachidonic acid followed, but oleic acid could not be oxidized. From linoleic acid the protein formed 9- and 13-hydroperoxides to the same extent, and both were shown to be racemic. These results showed that the oxidizing activity is accountable to a cytochrome, but not to a typical lipoxygenase. PMID- 11204195 TI - Production of xanthones with free radical scavenging properties, emodin and sclerotiorin by the cultured lichen mycobionts of Pyrenula japonica. AB - From the cultures of the spore-derived mycobionts of the lichen Pyrenula japonica, two new xanthones, 1,8-dihydroxy-3-hydroxymethyl-5-methoxyxanthone and 1,2,8-trihydroxy-5-methoxy-3-methylxanthone, were isolated along with 1,7 dihydroxy-3-methylxanthone, 1,5,8-trihydroxy-3-methylxanthone, 1,8-dihydroxy-5 methoxy-3-methylxanthone, emodin and sclerotiorin. Their structures were determined by spectroscopic methods. Sclerotiorin was isolated for the first time from lichen mycobionts. Radical scavenging activities of the isolated xanthones were also studied. PMID- 11204196 TI - A direct, highly sensitive fluorometric assay for a microsomal cytochrome P450 mediated O-demethylation using a novel coumarin analog as substrate. AB - A highly sensitive fluorometric assay for the determination of monooxygenase activity in liver microsomes is described. The assay is based on the use of 3 chloro-7-methoxy-4-methylcoumarin which is demethylated to 3-chloro-7-hydroxy-4 methylcoumarin. The rate of formation of 3-chloro-7-hydroxy-4-methylcoumarin was recorded as an increase of fluorescence (lambdaA = 380 nm, lambdaF = 480 nm) with time. When 3-chloro-7-methoxy-4-methylcoumarin was incubated in the presence of MgCl2 and NADPH with rat liver microsomes, a continuous increase of the fluorescence could be measured. The reaction proceeded linearly for about 10 min and at least up to a concentration of 0.1 mg/ml of microsomal protein. Besides 3 chloro-7-hydroxy-4-methylcoumarin a hydroxylated derivative of the substrate was formed as a second metabolite during the incubation. Using an excitation wavelength of 380 nm and a fluorescence/emission wavelength of 480 nm, the fluorescence of this substance (lambdaA = 338 nm, lambdaF = 422 nm) amounted only to about 1% of the fluorescence of the main product. The use of 3-chloro-7 methoxy-4-methylcoumarin as substrate enables the fluorometric determination of the O-dealkylation activity of a cytochrome P450-dependent monooxygenase system in rat liver which is inducible by phenobarbital but not by 3-methylcholanthrene. PMID- 11204197 TI - Removal of magnesium by Mg-dechelatase is a major step in the chlorophyll degrading pathway in Ginkgo biloba in the process of autumnal tints. AB - Autumnal tints are one of the most manifest and fascinating natural phenomena, but the mechanism of chlorophyll (Chl)-breakdown in deciduous trees has not been fully elucidated. In this study, we analyzed the composition of Chl-related compounds and determined the activities of initial Chl-degrading enzymes in Ginkgo leaves at various stages in the process of autumnal coloring. Only pheophytin a (Pheo a, Mg-free Chl a) was detected in yellow leaves by HPLC analysis, and the activity of Mg-dechelatase in yellow leaves was found to be higher than in green leaves. These findings showed that the removal of magnesium from Chl a occurred in advance of dephytylation in the Ginkgo. PMID- 11204198 TI - Interrelation between cyanophycin synthesis, L-arginine catabolism and photosynthesis in the cyanobacterium Synechocystis sp. strain PCC 6803. AB - Ultrastructural and immunocytochemical investigations gave evidence that cyanophycin (multi-L-arginyl-poly-L-aspartate) granules accumulate in the cyanobacterium Synechocystis sp. strain PCC 6803 under nutrient deficient growth conditions, especially under phosphate limitation. Besides nutrient deficiency, growth of Synechocystis PCC 6803 on L-arginine or L-asparagine as sole N-source also led to high increase of cyanophycin synthesis, while growth on the combination of L-arginine or L-asparagine with nitrate only caused minor cyanophycin accumulation. Growth of Synechocystis PCC 6803 on L-arginine as sole N-source caused substantial morphological and physiological changes, such as severe thylakoid membrane degradation with partial loss of pigments and photosynthetic activity leading to a phenotype almost like that seen under nutrient deficiency. In contrast to the wild type, the PsbO-free Synechocystis PCC 6803 mutant could grow on L-arginine as sole N-source with only minor morphological and physiological changes. Due to its fairly balanced growth, the mutant accumulated only few cyanophycin granules. L-arginine degrading activity (measured as ornithine and ammonium formation) was high in the PsbO-free mutant but not in the wild type when cells were grown on L-arginine as sole N-source. In both cells types the L-arginine degrading activity was high (although in the PsbO free mutant about twice as high as in wild type), when cells were grown on L arginine in combination with nitrate, and as expected very low when cells were grown on nitrate as sole N-source. Thus, net cyanophycin accumulation in Synechocystis PCC 6803 is regulated by the relative concentration of L-arginine to the total nitrogen pool, and the intracellular L-arginine concentration is greatly influenced by the activity of the L-arginine degrading enzyme system which in part is regulated by the activity status of photosystem II. These results suggest a complex interrelation between cyanophycin synthesis, L-arginine catabolism, and in addition photosynthesis in Synechocystis PCC 6803. PMID- 11204199 TI - A study on the heterogeneity of the light-harvesting complex II from Ectothiorhodospira sp. after acid/chaotropic treatment. AB - The light-harvesting complex II of the purple bacteria has two strong near infrared electronic absorption bands, around 800 (B800) and 850 (B850) nm, arising from the Qy transitions of bacteriochlorophyll a. It was previously reported that under some specific acid/chaotropic conditions the B850 bacteriochlorophylls of the light-harvesting complex II of Ectothiorhodospira sp. are strongly reorganised. Part of these pigments absorbs at 843 nm while another set absorbs around 858 nm. The current work should investigate whether a mix of two different complexes could generate the 843- and 858-nm bands. Acid/chaotropic conditions inducing the reorganisation of B850 were reproduced on a sample bound to an ionic-exchange column. The chromatographic pattern was found strongly homogeneous. The findings indicate that the heterogeneity of the reorganised B850 results from two forms of differently structured bacteriochlorophylls bound to the same polypeptide backbone. PMID- 11204200 TI - Transport of resistance-inducing sterols in phloem sap of barley. AB - After root application of [7alpha-3H]-7beta-hydroxysitosterol and [3alpha,6beta 3H2]-6alpha-hydroxylathosterol these sterols could be detected in the leaves and phloem sap feeding aphids. These results imply that the phloem sap is a sterol transport system in barley plants. PMID- 11204201 TI - Wound-induced respiration and pyrophosphate:fructose-6-phosphate phosphotransferase in potato tubers. AB - A seven fold increase in the rate of respiratory O2 uptake was observed 24 h after slicing of potato tuber disks. The maximum activity of pyrophosphate:fructose-6-phosphate phosphotransferase (PFP) was 5-7 times greater than that of ATP-dependent phosphofructokinase (PFK) in fresh or aged potato slices. Thus, PFP may participate in glycolysis which supplies respiratory substrate in potato tubers. The PFP activity of desalted extracts determined in the absence of fructose-2,6-bisphosphate (F2,6BP) increased by 4.5 fold 24 h after slicing. However, maximal PFP activity determined with saturating (1 microM) F2,6BP was not changed. The Ka values of PFP for F2,6BP was lowered from 33 to 7 nM after 24 h of aging treatment. This increased susceptibility of the PFP activity to its allosteric activator, F2,6BP, may be involved in the increased respiration in wounded disks of potato tubers. Immunoblotting experiments indicated that both the alpha (66 kDa) and the beta (60 kDa) subunits of PFP were present in fresh or 24 h aged tuber slices. PMID- 11204203 TI - 10-Hydroxystearic acid--identified after homogenization of tissue--is derived from bacteria. AB - 10-Hydroxystearic acid seems to be widely distributed in nature: Bacteria generate it by hydroxylation of oleic acid, but it was found also as constituent of plants, in cancer cell cultures and in mammalian tissue homogenates. Investigation of 10-hydroxystearic acid, obtained from mammalian tissue homogenates, revealed its identity with that of bacteria. Thus not 10 hydroxystearic acid is widely distributed in nature but its producers: bacteria. When biological material is processed in aqueous media, lipases are activated, these cleave membrane phospholipids. Thus liberated oleic acid is the substrate for widespread bacteria which are introduced into the media when the work up procedure is done in not sterile surrounding. The bacteria transform then oleic acid to 10R-hydroxystearic acid. PMID- 11204202 TI - The role of lipid peroxidation in aluminium toxicity in soybean cell suspension cultures. AB - The primary reactions leading to Al toxicity in plant cells have not yet been elucidated. We used soybean (Glycine max [L.] Merr.) cell suspension cultures to address the question whether lipid peroxidation plays an important role in Al toxicity. Upon transfer to an Al-containing culture medium with a calculated Al3+ activity of 15 microM soybean cells showed a distinct and longtime increase in lipid peroxidation within 4 h. At the same time a drastic loss of cell viability was observed. Butylated hydroxyanisole (BHA) and N,N'-diphenyl-p-phenylenediamine (DPPD), two lipophilic antioxidants, were able to almost completely suppress lipid peroxidation in Al-treated cells at a concentration of 20 microM. This effect was dose-dependent for DPPD and was observed at minimum concentrations of 1-2 microM. When lipid peroxidation was suppressed by DPPD or BHA cell viability remained high even in the presence of toxic Al concentrations. These results suggest that Al-induced enhancement of lipid peroxidation is a decisive factor for Al toxicity in suspension cultured soybean cells. PMID- 11204204 TI - Enzymatic hydrolysis of carotenoid fatty acid esters of red pepper (Capsicum annuum L.) by a lipase from Candida rugosa. AB - Analyses of red pepper extracts which had been pretreated with lipase type VII (EC 3.1.1.3.) from Candida rugosa showed for the first time pepper carotenoid esters to be substrates of this enzyme. However, the extent of enzymatic hydrolysis depends on the respective carotenoid and was not quantitative compared to chemical saponification. After enzymatic cleavage, 67-89% of total capsanthin, 61-65% of total zeaxanthin, 70-81% of total beta-cryptoxanthin and 70-86% of total violaxanthin were detected in free form. Nevertheless, the method described here offers the possibility to cleave in part several carotenoid esters originating from red pepper quickly and under comparatively mild reaction conditions. Replacement of the generally performed alkaline hydrolysis by enzymatic cleavage allows the resulting product to be used in food industry as "natural" coloring agent e.g. to colour cheese and jellies. PMID- 11204205 TI - Antioxidative activity of some quaternary ammonium salts incorporated into erythrocyte membranes. AB - The antioxidative activity of two series of amphiphilic compounds from a group of quaternary ammonium salts has been investigated. They were so-called bifunctional surfactants synthesized to be used as common pesticides or as antioxidants. The latter application was to be ensured by providing the compounds studied with an antioxidant group. Studies on antioxidative possibilities of those compounds were performed on pig erythrocytes. Due to their hydrophobic parts, they anchor in the erythrocyte membrane and influence the degree of lipid oxidation in the erythrocyte membrane subjected to UV radiation. It was found that compounds of both series decreased the oxidation of the membrane lipids. The inhibition of this oxidation increased with the length of their hydrophobic chains up to fourteen carbon atoms. The compounds of the longest hydrophobic chains showed a somewhat weaker antioxidative activity. Of the two series studied compounds were more effective having bromide ions as counterions. The corresponding compounds of a second series (chlorides) protected erythrocyte significantly weaker against oxidation. The effect of the compounds on fluidity of the erythrocyte membrane has been studied in order to explain the oxidation results. Change in fluidity of the erythrocyte ghost membranes was found also dependent on length of the hydrophobic part of the compounds and was more pronounced in the case of bromide surfactants. The final conclusion is that the compounds studied can be succesfully used as antioxidant agents of good efficacy. PMID- 11204206 TI - Transformations of 12,13-epoxy-11-hydroxy-9-octadecenoic acid and 4,5-epoxy-N acetylsphingosine by incubation with liver homogenate and liver microsomes. AB - Transformation of 12,13-epoxy-11-hydroxy-9-octadecenoic acid and 4,5-epoxy-N acetylsphingosine by addition of porcine liver homogenate and human liver microsomes, respectively was investigated. Both epoxides were converted to corresponding dioles by porcine liver homogenate, but not by human liver microsomes, suggesting location of the hydrolyzing enzymes not in the microsomes, but within the cell wall. PMID- 11204207 TI - PCR-based identification of Bacillus thuringiensis isolated from soil samples in Nigeria. AB - Six isolates of Bacillus thuringiensis isolated from soil samples confirmed to be toxic to mosquito larvae were differentiated using a PCR-Based technique. Three of these isolates initially identified using a serological technique were further differentiated with the PCR amplification of the delta-endotoxin target sequences. Using the total DNA of isolates as template, at least four isolates yielded amplicons one or all the crystal protein genes, cryI a, b, c, or II with sizes ranging from 238-1070 bp. None of these isolates yielded an amplicon for any of Cry IV A, B and D tested. Of the four isolates identified by PCR technique one isolate remained unidentified by serology. PMID- 11204208 TI - Cyanophora paradoxa: nucleotide sequence and phylogeny of the nucleus encoded muroplast fructose-1,6-bisphosphate aldolase. AB - Immunoscreening of a C. paradoxa expression library against water soluble muroplast ("cyanelle") proteins resulted in isolation of a clone encoding the nucleus-encoded muroplast class-II fructose-1,6-bisphosphate aldolase (class-II FBA). Its nucleotide sequence was determined. The 1432 bp insert, derived from a single-copy gene transcript, bears a reading frame of 1206 bp in length, representing 402 amino acids with 346 amino acids of mature protein. The leading amino acids match structural features necessary for precursor import across chloroplast envelope membranes. In phylogenetic tree topology, the investigated mature FBA clusters within type B FBAs with Synechocystis sp. as nearest neighbor. This is the first report of a Type B class-II FBA sequence of plastids. PMID- 11204209 TI - Determination of phenolic flame-retardants in human plasma using solid-phase extraction and gas chromatography-electron-capture mass spectrometry. AB - A method for determination of phenolic flame-retardants in human plasma utilizing solid-phase extraction (SPE) and gas chromatography with electron-capture mass spectrometric detection (GC-ECMS), has been developed. The plasma lipids were decomposed by application of concentrated sulphuric acid directly on the polystyrene-divinylbenzene SPE column. The method has been validated for 2,4,6 tribromophenol (TriBP), pentabromophenol (PeBP), tetrachlorobisphenol-A (TCBP-A) and tetrabromobisphenol-A (TBBP-A) in the concentration range 1.2-25, 0.4-40, 4 200 and 4-200 pg g(-1) plasma, respectively. The average absolute recovery of the analytes ranged from 51 to 85%. Tetrabromo-o-cresol and chlorotribromobisphenol-A were found suitable as internal standards, and the average recovery of the analytes relative to the internal standards was in the range 93-107%. The repeatability of the method was in the range 4-30% relative standard deviation. The estimated detection limits of TriBP, PeBP, TCBP-A and TBBP-A were 0.3, 0.4, 3.0 and 0.8 pg g(-1) plasma, respectively. The method has been used for analysis of plasma samples from potentially occupationally exposed human individuals. PMID- 11204210 TI - New procedures for glycophorin A purification with high yield and high purity. AB - Glycophorin A (GPA) is the major glycoprotein of the human erythrocyte membrane. It is known to form, in SDS gels as well as in a membrane environment, homodimers, and also heterodimers with the homologous molecule Glycophorin B (GPB). It is shown in this report that the propensity of GPA to dimerize with GPB precludes satisfactory preparation with high yield of pure GPA using classical techniques including SEC and RPLC. It was demonstrated using multiple angle light scattering that GPA is eluted from RPLC columns as dimers. A convenient procedure was devised which allowed us to get pure GPA with high yield. This procedure consists of selectively blocking GPA-GPB heterodimer formation by selective modification of Cysteine 50 of GPB before RPLC. PMID- 11204211 TI - Determination of scopolamine in human serum and microdialysis samples by liquid chromatography-tandem mass spectrometry. AB - A liquid chromatographic-tandem mass spectrometric (LC-MS-MS) method with a rapid and simple sample preparation was developed for the determination of scopolamine in biological fluids. Scopolamine and the internal standard atropine in serum samples were extracted and cleaned up by using an automated solid phase extraction method. Microdialysis samples were directly injected into the LC-MS system. The mass spectrometer was operated in the multi reaction monitoring mode. A good linear response over the range of 20 pg/ml to 5 ng/ml was demonstrated. The accuracy for added scopolamine ranged from 95.0 to 104.0%. The lower limit of quantification was 20 pg/ml. This method is suitable for pharmacokinetic studies. PMID- 11204212 TI - Detection of a mixed-backbone oligonucleotide (GEM 231) in liver and tumor tissues by capillary electrophoresis. AB - A simple, rapid and sensitive method has been developed and validated for the analysis of a mixed-backbone oligonucleotide (GEM 231) in tumor tissues. The analysis was performed using a capillary electrophoresis (CE) system with UV detection. An extended light path (bubble cell) capillary column of 64.5 cm (effective length 56 cm) x 50 microm I.D. is used as the separation column. The optimized chromatographic conditions were background electrolyte: sodium borate buffer (60 mM, pH 9.1), electrokinetic injection: 10 s, applied voltage: 30 kV, detection at lambda = 210 nm. A linear relationship was observed between the peak area and the amount of GEM 231 in the range of 1.0-1000 microg/ml. The lower detection limit of the drug was 100 pg with an average recovery of about 75 +/- 5%. The inter-day and intra-day relative standard deviations were <10%. Assay validation studies revealed that CE method is reproducible and specific for the determination of GEM 231 in tissue homogenates with a run time of less than 5 min. PMID- 11204213 TI - Quantitative determination of L-775,606, a selective 5-hydroxytryptamine 1D agonist, in rat plasma using automated sample preparation and detection by liquid chromatography-tandem mass spectrometry. AB - L-775,606 is under investigation as a selective 5-hydroxytryptamine 1D agonist for the treatment of migraine. A reliable and sensitive method for the analysis of L-775,606 in plasma was required in order to support preclinical evaluation of this compound. A semi-automated sample preparation method using the Beckman Biomek 2000 workstation to perform all liquid handling tasks has been established. The sample analysis was performed using HPLC-MS-MS with a cycle time of 3.5 min per sample. Intra- and inter-day assay accuracy and precision are excellent with a calibration range of 1-2000 ng/ml and a reproducible limit of quantification of 1 ng/ml. PMID- 11204214 TI - A sensitive high-performance liquid chromatographic method using electrochemical detection for the analysis of olanzapine and desmethylolanzapine in plasma of schizophrenic patients using a new solid-phase extraction procedure. AB - A high-performance liquid chromatographic method with amperometric detection for the analysis of the novel antipsychotic drug olanzapine and its metabolite desmethylolanzapine in human plasma has been developed. The analysis was carried out on a reversed-phase column (C8, 150 x 4.6 mm I.D., 5 microm) using acetonitrile-phosphate buffer, pH 3.8, as the mobile phase. The detection voltage was + 800 mV and the cell and column temperature was 30 degrees C. The flow-rate was 1.2 ml min(-1). Linear responses were obtained between 5 and 150 ng ml(-1), with repeatability <3.3%. A careful pretreatment of the biological samples was implemented by means of solid-phase extraction (SPE) on C8 cartridges. The method requires 500 microl of plasma for one complete analysis. Absolute recovery exceeded 97% for both olanzapine and desmethylolanzapine, and the detection limit was 1 ng ml(-1) for both analytes. Repeatability, intermediate precision and accuracy were satisfactory. This sensitive and selective method has been successfully applied to therapeutic drug monitoring in schizophrenic patients treated with Zyprexa tablets. PMID- 11204215 TI - Improved use of the [13C]octanoic acid breath test as intra-individual parameter to study the effect of a prokinetic drug on gastric emptying in preterm infants with oral feeding intolerance. AB - The [13C]octanoic acid breath test was used for the measurement of differences in gastric emptying in preterm infants for the evaluation of pharmacological therapy. In order to perform a good intra-individual comparison of the gastric emptying in preterm infants under non-standardisable test conditions, we adjusted t1/2 for variations in non-recovered label (=label retention) and introduced an "effective half 13CO2 breath excretion time" t1/2eff = t1/2/m expressed as min per percentage of the cumulative dose recovered. In a pilot study, we investigated the action of the gastrointestinal prokinetic drug cisapride on gastric emptying in seven premature infants, of whom four suffered from gastric stasis and three had constipation. The postnatal age and weight at the start of treatment ranged from 15 to 64 days and from 815 to 1635 g, respectively. All infants received the standard formula for premature infants (Nenatal, Nutricia). Cisapride was administered orally 0.2 mg/kg, four times daily. The changes in gastrointestinal motility were studied using the total bowel transit time of carmine red. After 7 days of treatment in all children, the gastric emptying coefficient and the half 13CO2 breath excretion time adjusted for label retention were improved (n=7, the gastric emptying coefficient range before treatment was 1.69-3.34 (mean 2.59 +/- 0.80) and after treatment it was 2.79-3.76 (mean 3.28 +/ 0.30); the half 13CO2 breath excretion time adjusted for label retention range before treatment was 3.0-14.7 min/% dose (mean 7.0 +/- 5.0) and after treatment 2.6-4.0 min/% dose (mean 3.1 +/- 0.6). The total bowel transit time was only slightly improved in two patients (n=7, mean total bowel transit time before: 23.7 h compared to mean total bowel transit time after 7 days of treatment: 35.5 h). Side effects during cisapride treatment were not seen. We conclude that in premature infants cisapride is effective in shortening gastric emptying time and reducing gastric stasis; the therapeutic role in constipation has to be further investigated. PMID- 11204216 TI - Liquid chromatographic assay for simultaneous determination of abacavir and mycophenolic acid in human plasma using dual spectrophotometric detection. AB - A combined bio-analytical assay for abacavir, a reversed transcriptase inhibitor, and mycophenolic acid (MPA), based on reversed-phase liquid chromatography and both ultraviolet (UV) absorption and fluorescence detection, is reported. Both analytes are extracted from plasma with acetonitrile. After centrifugation, evaporation of the supernatant and reconstitution in water, the sample is injected into the chromatograph. Abacavir is detected using UV detection at 285 nm and MPA spectrofluorometrically at 345 and 430 nm for excitation and emission, respectively. The method has been validated in the 80-2000 ng/ml range for abacavir and in the 10-10,000 ng/ml range for MPA for 200-microl plasma samples. The lower limits of quantification are 80 and 10 ng/ml for abacavir and MPA, respectively. Precisions and accuracies are < or = 8% in the valid concentration ranges of both analytes. PMID- 11204217 TI - High-performance liquid chromatographic-tandem mass spectrometric determination of 3-hydroxypropylmercapturic acid in human urine. AB - A sensitive and specific high-performance liquid chromatographic-tandem mass spectrometric (HPLC-MS-MS) method was developed for the determination of 3 hydroxypropylmercapturic acid (3-HPMA) in human urine. Samples were extracted using ENV+ cartridges and then injected onto a C8 Superspher Select B column with acetonitrile and formic acid as eluent (5:95, v/v). N-Acetylcysteine was used as internal standard for HPLC-MS-MS. Linearity was given in the tested range of 50 5000 ng/ml urine. The limit of quantification was 50 ng/ml. Precision, as C.V., in the tested range of 50-5000 ng/ml was 1.47-6.04%. Accuracy ranged from 87 to 114%. 3-HPMA was stable in human urine at 37 degrees C for 24 h. The method was able to quantify 3-HPMA in urine of non-smokers and smokers. PMID- 11204218 TI - Simultaneous determination of cefotaxime and desacetylcefotaxime in human plasma and cerebrospinal fluid by high-performance liquid chromatography. AB - A simple and sensitive HPLC method for the simultaneous determination of cefotaxime (I) and desacetylcefotaxime (II) in human plasma and cerebrospinal fluid (CSF) is described. The assay involves deproteinisation and subsequent separation on a reversed-phase HPLC column, with ultraviolet detection at 262 nm. Retention times were 6.8 and 2.2 min for cefotaxime and desacetylcefotaxime, respectively. Average recoveries for the analytes were 78% (I) and 88% (II) from both matrices. Linear responses were observed over a wide range (0.58-940 microg/ml for (I) in plasma, 0.80-55.8 microg/ml for (I) in CSF, 0.54-148 microg/ml for (II) in plasma and 0.50-36.0 microg/ml for (II) in CSF). PMID- 11204219 TI - Optimised determination of clobazam in human plasma with extraction and high performance liquid chromatography analysis. AB - The analysis of clobazam by high-performance liquid chromatography and UV detection is described herein. After adding an internal standard, 600 microl of plasma were extracted under basic conditions onto disposable cartridges packed with celite. The organic extract was then evaporated to dryness and the residue reconstituted in 200 microl of mobile phase. A 20 microl aliquot was injected into chromatograph. The HPLC system was equipped with an Ultrasphere C8 analytical column coupled with an UV detector set at 235 nm. The mobile phase was an acetate buffer 20 mM, pH 5.5, containing acetonitrile and triethylamine 70:30:0.01 (v/v); the flow-rate was 1.8 ml/min. Using this method, clobazam can be detected with a sensitivity limit of 6 ng/ml and the RSD% intra- and inter assay were lower than 5%. For its ruggedness and reliability, the proposed method is particularly suitable for therapeutic drug monitoring in epilepsy. PMID- 11204220 TI - Determination of 5-fluorouracil in environmental samples by solid-phase extraction and high-performance liquid chromatography with ultraviolet detection. AB - 5-Fluorouracil (5-FU) is one of the most widely used antineoplastic drugs. It can be therefore considered to be a model compound for the identification of exposure routes during preparation and administration of cytostatic agents, especially for nucleoside analogue drugs. In this study, an HPLC-UV method was validated for determination of 5-FU in wipe samples by direct analysis of the aqueous solutions and in air samples by using solid-phase extraction (SPE). When samples were pre treated on styrene-divinylbenzene resin SPE columns, a 20-fold preconcentration of the analyte was achieved. As regards air samples, correlation coefficients were always higher than 0.998 and the limit of detection was assessed at 15 ng on filter. In order to verify the reliability of these procedures, 5-chlorouracil was used as internal standard. The procedure presented here has been applied to the environmental monitoring of occupational exposed subjects. The amount of 5-FU ranged from 0.043 to 0.23 microg/m3 in air samples and from 0.2 to 470.1 microg/dm2 in wipe samples. 5-FU was also detected on the internal side of the gloves (0.07 to 3.77 microg/pair of gloves). PMID- 11204221 TI - Determination of urine catecholamines by capillary electrophoresis with dual electrode amperometric detection. AB - Demonstrated in this study is that without pretreatment and preconcentration nanomolar-level catecholamines in human urine samples can be quantitatively determined with ease by utilizing capillary electrophoresis coupled with amperometric detection. The detector employs a parallel-opposed dual-electrode scheme assembled with an on-capillary electrode and a disk electrode and takes advantage of the redox cycling of analytes between the two working electrodes to improve the limit of detection. The matrix effect of urine samples significantly decreases the detection sensitivity from that obtained in standard solutions. Therefore, calibration curves derived from standard solutions cannot be used in quantitative determination of catecholamines. Methods of standard addition and internal standard have been studied. The results suggest that isoproterenol is a good internal standard to facilitate the measurements of dopamine, epinephrine, and norepinephrine in human urine samples. PMID- 11204222 TI - Simple and sensitive high-performance liquid chromatographic method for the determination of 1,5-benzodiazepine clobazam and its active metabolite N desmethylclobazam in human serum and urine with application to 1,4 benzodiazepines analysis. AB - A HPLC-UV determination of clobazam and N-desmethylclobazam in human serum and urine is presented. After simple liquid-liquid extraction with dichloromethane the compounds and an internal standard diazepam were separated on a Supelcosil LC 8-DB column at ambient temperature under isocratic conditions using the mobile phase: CH3CN-water-0.5 M KH2PO4-H3PO4 (440:540:20:0.4, v/v and 360:580:60:0.4, v/v for serum and urine, respectively). The detection was performed at 228 nm with limits of quantification of 2 ng/ml for serum and 1 ng/ml for urine. Relative standard deviations for intra- and inter-assay precision were found below 8% for both compounds for all the tested concentrations. The described procedure may be easily adapted for several 1,4-benzodiazepines. PMID- 11204223 TI - Avidin-biotin-immobilized liposome column for chromatographic fluorescence on line analysis of solute-membrane interactions. AB - Unilamellar liposomes with entrapped fluorescent dye calcein were stably immobilized in gel beads by avidin-biotin-binding. The immobilized liposomes remained extremely stable upon storage and chromatographic runs. The immobilized calcein-entrapped liposomes were utilized for fluorescent analysis of solute membrane interactions, which in some cases are too weak to be detected by chromatographic retardation. A liposome column was used as a sensitive probe to detect the interactions of membranes with pharmaceutical drugs, peptides and proteins. Retardation of the solutes was monitored using a UV detector. Perturbation of the membranes, reflected as leakage of the entrapped calcein by some of the solutes, can thus be detected on-line using a flow-fluorescent detector. For the amphiphilic drugs or synthetic peptides, perturbation of membranes became more pronounced when the retardation (hydrophobicity) of the molecules increased. On the other hand, in the case of positively-charged peptides, polylysine, or partially denatured bovine carbonic anhydrase, significant dye leakage from the liposomes was observed although the retardation was hardly to be measured. Weak protein-membrane interactions can thus be assumed from the large leakage of calcein from the liposomes. This provides additional useful information for solute-membrane interactions, as perturbation of the membranes was also indicated by avidin-biotin-immobilized liposome chromatography (ILC). PMID- 11204224 TI - On-line deproteinization by adsorption of proteins on a polyethylene powder pre column for the determination of Na, K, Mg and Ca in human serum by high performance liquid chromatography. AB - Deproteinization of human serum was carried out on-line using a polyethylene powder cartridge as pre-column. The serum sample, after dilution, was injected into the chromatograph, and when passing through the cartridge the proteins were adsorbed by the polyethylene. A protein-free eluate was carried to the analytical column while the pre-column was washed with methanol and water to elute the adsorbed proteins by changing the pump channels. After washing, the pre-column was conditioned with the eluent to receive the next sample. Deproteinization was evaluated off- and on-line using pooled serum, and testing the protein residue after passing through a polyethylene cartridge with the Comassie Brilliant Blue reaction. Parameters such as serum volume, eluent and washing solution were investigated. Sodium, potassium, magnesium and calcium determinations were performed by high-performance liquid chromatography with conductimetric detection. The proposed method is suitable for the determination of these cations in serum samples without further treatments. The total analysis time was about 20 min and a linear range from 0.3 to 1.2 mg/l for sodium, potassium, magnesium and calcium was observed. The method was characterized by a precision of about 95% and recoveries from spiked samples were between 96 and 102%. The results for serum samples analysed by the proposed method were compared with photometry and atomic absorption spectrometry. PMID- 11204225 TI - Analysis of histidine and urocanic acid isomers by reversed-phase high performance liquid chromatography. AB - The qualitative separation performance of a C18, C8 and C4 reversed-phase column was investigated for the separation of histidine and its metabolites histamine, 1 methyihistamine and trans- and cis-urocanic acid. Trans- and cis-urocanic acid were baseline separated from their precursor histidine on all three columns using isocratic elution with a mobile phase composed of 0.01 M aqueous TEAP pH 3.0 and acetonitrile at a ratio of 98:2 (v/v). However, histidine was not separated from histamine and 1-methyihistamine. Selecting the C8 column and introducing 0.005 M of the ion pairing reagent 1-octanesulfonic acid sodium salt into the aqueous solution and acetonitrile at a ratio of 90:10 (v/v), significantly improved the separation. The separation was also followed by a change in the retention times and the order of elution. The sequence of elution was histidine, cis-urocanic acid, trans-urocanic acid, histamine and 1-methylhistamine with retention times of 5.58 +/- 0.07, 7.03 +/- 0.15, 7.92 +/- 0.18, 18.77 +/- 0.24 and 20.79 +/- 0.21 min (mean +/- SD; n=5). The separation on the C8 column in the presence of the ion-pairing reagent was further improved with gradient elution that resulted in a reduction in the retention times and elution volumes of histamine and 1 methylhistamine. The detection limits of histidine and trans-urocanic acid at a wavelength of 210 nm and an injection volume of 0.05 ml were 5 x 10(-8) mol l(-1) (n=3). The kinetic of the in-vitro conversion of trans- into the cis-isomer after UV irradiation was depending on the time of exposure and the energy of the light source. UVB light induced a significantly faster conversion than UVA light. TUCA and cUCA samples kept at -25 degrees C were stable for up to 50 weeks. Samples, eluted from human skin showed various concentrations of histidine and trans- and cis-urocanic acid with an average of 1.69 +/- 0.33 x 10(-5) mol l(-1), 1.17 +/- 0.43 x 10(-5) mol l(-1) and 1.67 +/- 0.33 x 10(-5) mol l(-1), respectively (n=8). PMID- 11204226 TI - Quantification of urine 17-ketosteroid sulfates and glucuronides by high performance liquid chromatography-ion trap mass spectroscopy. AB - The measurement of androgen steroids has been utilized as a clinical indicator of adrenal function, androgen abuse, and as a prediction of general health or biological aging. An improved high-performance liquid chromatography-ion trap mass spectroscopic method with sonic spray ionization (SSI) technology for the quantification of individual urinary 17-ketosteroid sulfates and glucuronides was developed and validated. Sample preparation was simplified using a C18 cartridge followed by direct injection onto a reversed-phase HPLC column. Individual 17 ketosteroid from 63 urinary specimens collected in a 24-h period was measured. 17 Ketosteroid conjugates, total 17-KS-S and the ratio of total 17-KS-S to creatinine referred to herein as the Anabolic/Catabolic Index (ACI) showed statistically significant negative correlations with age. PMID- 11204227 TI - Measurement and pharmacokinetic analysis of unbound ceftazidime in rat blood using microdialysis and microbore liquid chromatography. AB - To evaluate the biodisposition of ceftazidime in rat blood, a rapid and simple microbore liquid chromatographic technique together with a microdialysis sampling technique were developed. This method involves an on-line design for blood dialysate directly injected into a microbore liquid chromatographic system. The chromatographic conditions consisted of a mobile phase of methanol-acetonitrile 100 mM monosodium phosphoric acid (pH 3.0) (10:10:80, v/v/v) pumped through a microbore reversed-phase column at a flow-rate of 0.05 ml/min. With the detection wavelength set at 254 nm, a good linear correlation was observed between the peak area and the ceftazidime concentration at 0.1 to 50 microg/ml (r=0.999). Microdialysis probes, being custom-made, were screened for acceptable in vivo recovery while chromatographic resolution and detection were validated for response linearity, as well as intra-day and inter-day variabilities. This method was then applied to the pharmacokinetic profiling of ceftazidime in blood following intravenous 50 mg/kg administration to rats. The pharmacokinetics was calculated from the corrected data for dialysate concentrations of ceftazidime versus time. This method has been used to study ceftazidime pharmacokinetics in rats and has proven to be rapid and reproducible. PMID- 11204228 TI - Highly sensitive determination of TS-962 (HL-004), a novel acyl-CoA:cholesterol acyltransferase inhibitor, in rat and rabbit plasma by liquid chromatography and atmospheric pressure chemical ionization-tandem mass spectrometry combined with a column-switching technique. AB - A quantitative bioanalytical method with excellent specificity using liquid chromatography (LC) atmospheric pressure chemical ionization-tandem mass spectrometry (APCI-MS-MS) combined with a column-switching technique has been developed for the highly sensitive and reliable determination of TS-962 (HL-004), a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, in rat and rabbit plasma. The method involves protein precipitation of a 25-microl aliquot of plasma sample with eight volumes of methanol containing a deuterium-labeled internal standard, the direct injection of a methanolic supernatant into the analytical instrumentation with no sample evaporation and reconstitution steps, automated on-line clean-up on a C18 short trapping column (10 mm x 4.0 mm I.D.) followed by separation on a C18 analytical column (50 mm x 4.6 mm I.D.), and detection with APCI-MS-MS using m/z 448 ([M+H]+) as a precursor ion and m/z 178 as a product ion in a selected reaction monitoring mode. The lower limit of quantification was 1 ng/ml, and good linearity of the calibration graph was obtained in the range of 1 to approximately 490 ng/ml with excellent reliability. The developed method enabled pharmacokinetic profiles to be determined for rats and rabbits with sequential plasma collection from an individual animal. PMID- 11204229 TI - Artificial neural networks in liquid chromatography: efficient and improved quantitative structure-retention relationship models. AB - The application of the principal neural network architecture, namely the multilayer perceptron (MLP), has been developed for obtaining sufficient quantitative structure-retention relationships (QSRR) with high accuracy. The present study is an extension to the excellent study of Cserhati et al. [LC-GC Int., 11 (1998) 240] for the retention behavior of solutes based on their structure. To this end, a dataset of 25 substances as solutes to two different stationary phases (polyethylene-silica and polyethylene-alumina) were analyzed to their structural descriptors and related to their retention behavior as expressed by the logarithms of their capacity factors (log k'). The results were compared to those of Cserhati et al. who studied the same problem using as many as ten different equations based on multiple regression analysis. In the present study a series of new and improved algorithms other than the 'old-fashioned' and problematic steepest descent were examined for training the MLP networks. The proposed methods led to substantial gain in both the prediction ability and the computation speed of the resulting models. For the development and evaluation of the artificial neural network (ANN) systems the same (eight) descriptors proposed by Cserhati were used also in this study. Furthermore, the results were compared to those produced from classical linear multivariate regression such as partial least squares regression (PLS). Some of the proposed ANN models diminished the number of outliers, during their implementation to unseen data (solutes), to zero. PMID- 11204230 TI - Chelated mercury as a ligand in immobilized metal ion affinity chromatography of proteins. AB - Chelation of mercuric ions by an iminodiacetate-Sepharose gel was evaluated. The retentive properties of iminodiacetate-Sepharose gel column was studied towards proteins varying the composition of eluting systems from 2-mercaptoethanol to NaCl and imidazole, determining also the extent of mercury leaching. It was demonstrated that chelated mercury contained free sites for interaction with proteins such as bromelain and recombinant human granulocyte colony stimulating factor from E. coli. The extraction of the latter by chromatography of its inclusion bodies solution on Hg(II)-loaded Sepharose-iminodiacetate gel was also evaluated. PMID- 11204231 TI - Comparative studies of recombinant human granulocyte-colony stimulating factor, its Ser-17 and (His)6-tagged forms interaction with metal ions by means of immobilized metal ion affinity partitioning. Effect of chelated nickel and mercuric ions on extraction and refolding of proteins from inclusion bodies. AB - The chelation capability of the reactive dye Light Resistant Yellow 2KT towards metal ions, particularly mercury(II) was evaluated in the pH range 5.0-7.0, and it was shown that the dye-Hg(II) complex has a free site for the interaction with human recombinant granulocyte-colony stimulating factor (rhG-CSF) from Escherichia coli. Affinity partitioning of three rhG-CSF forms--native, rhG CSF[Cys17--->Ser17] and (His)6-rhG-CSF was studied in aqueous two-phase systems, which contained metal ions--Cu(II), Ni(II) and Hg(II)--chelated by dye poly(ethylene glycol) at pH 5.0 and 7.0, in the presence or absence of many selected agents. It was determined, that chelated Ni(II) ions exhibited stronger interaction with the hexahistidine-tagged protein form, while the extraction power of Cu(II) ions was found to be of comparable order of magnitude for all three protein forms at pH 7.0. A comparative study of rhG-CSF and both its forms partitioning in the presence of chelated Hg(II) ions at pH 7.0 and 5.0 revealed possible direct interaction between Hg(II) ions and unpaired Cys-17 of rhG-CSF. The partitioning of three rhG-CSF forms inclusion body extract was studied in the presence of chelated Ni(II) and Hg(II) ions thus explaining the efficiency of targeted proteins renaturation gained upon their inclusion body forms interactions with chelated metal ions. PMID- 11204233 TI - On-line membrane extraction liquid chromatography for monitoring semi-volatile organics in aqueous matrices. AB - Membrane extraction is an attractive alternative to conventional extraction methods, such as liquid-liquid extraction and solid phase extraction, because the analytes can be isolated in a continuous fashion. On-line detection can be carried out using a suitable analytical instrument. The objective of this study is to study the enrichment of semi-volatile organic compounds (SVOCs) from an aqueous matrix by on-line membrane extraction, to be followed by liquid chromatographic (ME-LC) analysis for continuous monitoring. The membrane serves as an interface across which liquid-liquid extraction takes place. The SVOCs transfer from the aqueous phase and are concentrated in an organic extractant. The enriched solvent is intermittently injected into an HPLC for analysis. In this paper, the enrichment into the organic phase under different operating conditions and the performance characteristics of the instrumentation are presented. PMID- 11204232 TI - Development of an automated on-line solid-phase extraction-high-performance liquid chromatographic method for the analysis of aniline, phenol, caffeine and various selected substituted aniline and phenol compounds in aqueous matrices. AB - A fully automated solid-phase extraction (SPE)-high-performance liquid chromatographic method has been developed for the simultaneous analysis of substituted anilines and phenols in aqueous matrices at the low- to sub-microg/l level. Diode array and electrochemical detection operated in tandem mode were used for analyte detection. Two new polymeric sorbent materials (Hysphere-GP and Hysphere-SH) were evaluated for the on-line SPE of substituted anilines and phenols from aqueous matrices and their performance was compared with the PRP-1 and PLRP-S sorbents. Hysphere-GP sorbent packed in 10 x 2 mm cartridges was found to give better results in terms of sensitivity and selectivity of the overall analytical method. The proposed analytical method was validated for the analysis of these compounds in Axios river water that receives industrial, communal and agricultural wastes. The detection limits for all the compounds range between 0.05 and 0.2 microg/l, except for aniline and phenol which have detection limits of 0.5 and 1 microg/l, respectively (aniline detected by electrochemical detection). The recoveries for all the compounds are higher than 75% except for aniline (6%), phenol (50%) and 3-chlorophenol (67%). Finally, in order to evaluate the efficiency of the Hysphere-GP (10 x 2 mm) cartridges for sample stabilization and storage, the stability of the compounds of interest at the sorbed state onto these cartridges has been evaluated under three different temperature regimes (deep freeze, refrigeration, 20 degrees C). PMID- 11204234 TI - High-performance liquid chromatographic determination of linoleic acid peroxide derived radicals using electrochemical detection. AB - High-performance liquid chromatography-electrochemical detection (HPLC-ED) was applied to detect 13-hydroperoxide octadecadienoic acid (13-HPODE)-derived radicals such as the pentyl radical and octanoic acid radical. The 13-HPODE derived radicals were successfully detected using HPLC-ED by the combined use of the spin-trapping technique with alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4 POBN). The 4-POBN-pentyl radical adduct was detected at the retention time of 18.2 +/- 0.3 min on the elution profile of HPLC-ED with an ODS column (15 cm x 4.6 mm I.D.) using a flow-rate of 1.0 ml/min with 50 mM ammonium acetate in 29% (v/v) aqueous acetonitrile. The 4-POBN-octanoic acid radical adduct was also detected at the retention time of 13.7 +/- 0.7 min using a flow-rate of 1.0 ml/min with 50 mM ammonium acetate in 14% (v/v) aqueous acetonitrile. The concentrations of the 4-POBN radical adducts were determined using HPLC-ED without an internal standard. HPLC-ED is 100 times as sensitive as HPLC-electron spin resonance (ESR) under the ESR and ED conditions employed here. Even 1.8 pmol of the 4-POBN-pentyl (or octanoic acid) radical adduct was detectable using PMID- 11204235 TI - Determination of 16beta-hydroxystanozolol in urine and faeces by liquid chromatography-multiple mass spectrometry. AB - This paper describes the optimisation of the detection of stanozolol and its major metabolite 16beta-hydroxystanozolol in faeces and urine from cattle. Faeces are extracted directly with diisopropyl ether. Urine is first submitted to an enzymatic hydrolysis and then extracted over a modified diatomaceous earth column (Chem-Elut) with a mixture of diisopropyl ether-isooctane. In a final step an acidic back extraction is performed. For the LC-MS-MS detection two approaches are discussed. In a first approach the final extract is detected without derivatization, while the second approach makes use of a derivatization step for 16beta-hydroxystanozolol. While the MS-MS spectrum without derivatization exhibits extensive fragmentation, the spectrum of the derivative shows two abundant diagnostic ions with much more reproducible ion ratios. The derivatization method and the method without derivatization enable the detection of 16beta-hydroxystanozolol up to 0.03 microg l(-1) in urine and 0.07 microg kg( 1) in faeces. Until now there is no literature available for the detection of 16beta-hydroxystanozolol in faeces and urine at the ppt level. PMID- 11204236 TI - Pair-wise interactions by gas chromatography. VII. Interaction free enthalpies of solutes with secondary alcohol groups. AB - A polar type liquid having a secondary alcohol substituent on a branched alkane skeleton, SOH, was used as stationary phase. The molecules of this stationary phase are nearly isomorphous and isochor with those of the branched alkane, C78, elected as standard, i.e., the molecules of both solvents have nearly the same form and the same size. Partition properties of 158 chosen molecular probes were measured by gas chromatography on SOH and on an SOH-C78 mixture having a volume fraction of thetaOH = 0.5. Based on the resulting data an interaction free enthalpy could be calculated, i.e., the additional effect of the secondary alcohol to partition. Comparison with data determined earlier on another member of this solvent family, POH, having a primary alcohol as interacting group gives information about the effect of steric hindrance on polar type solute-solvent interaction free energies. PMID- 11204237 TI - Observation of exchangeable protons by high-performance liquid chromatography nuclear magnetic resonance spectroscopy and high-performance liquid chromatography-electrospray ionization mass spectrometry: a useful tool for the hyphenated analysis of natural products. AB - The first high-performance liquid chromatography-nuclear magnetic resonance (HPLC NMR) investigation of exchangeable protons of low-molecular-mass natural products is reported. Model alkaloids or crude plant extracts were dissolved in 2H2O-1H2O MeCN (deuterium oxide-water-acetonitrile) or 2H2O-MeCN and, after direct injection or chromatographic separation, examined in a 60-microl NMR flow probe. Exchangeable amino protons initially detected by HPLC-electrospray ionization mass spectrometry were subsequently identified and investigated by stop-flow 1H NMR, two-dimensional (2D) total correlation spectroscopy (TOCSY), and 2D nuclear Overhauser effect spectroscopy (NOESY). These experiments extend the applicability of HPLC-NMR for the investigation and structure elucidation of natural products. PMID- 11204238 TI - Immunoaffinity column clean-up prior to thin-layer chromatography for the determination of aflatoxins in various food matrices. AB - A one-dimensional TLC method to determine aflatoxins (B1, B2, G1, G2) in various food matrices was elaborated which abstains fully on the use of chlorinated solvents. It implements an immunoaffinity clean-up step after extraction with methanol. The aflatoxins were quantified by densitometry. The method has shown to be rapid and efficient. In-house performance characteristics were established. The limit of quantification was found to be significantly lower than current regulatory limits for aflatoxin control outside and within the European Community. The obtained recovery and precision data gave a strong indication, that the method is likely to give satisfactory performance if tested in a future collaborative trial. PMID- 11204239 TI - Development and validation of a high-performance liquid chromatographic method for the determination of clomazone residues in surface water. AB - A method is described for the determination of clomazone residues in surface water by high-performance liquid chromatography with UV detection. The method involves solid-phase extraction with C18 extraction tubes. Clomazone was separated on a C18 column with a mobile phase of methanol-water (65:35, v/v) at pH 4.0 and a flow-rate of 1.0 ml/min. After optimization of the extraction and separation conditions, the method was validated. The method developed can be used for determination of clomazone in surface water, at the limit of 0.1 mcirog/l set by the European Union drinking water directive, with a 400-fold preconcentration. PMID- 11204240 TI - Development of a simplified densitometer for the determination of aflatoxins by thin-layer chromatography. AB - A simple, miniaturised and low power consuming (battery, fully semiconductor based) detector cell (SeBaDeC) was developed for the densitometric measurement of aflatoxins on TLC plates. A UV-light emitting diode (UV-LED) with a peak emission wavelength of 370 nm was used for fluorescence excitation, while a photo diode with a peak sensitivity of 440 nm in combination with a 418 nm cut-off filter was applied for detecting the fluorescence intensity. The resulting signal was further amplified by means of a commonly used operational amplifier integrated circuit (OA) and directly converted into a digital signal with a simple analogue digital-converter (ADC). This signal was recorded at the serial (RS232) port of a portable PC and processed with a spreadsheet program. The software used for data recording is freeware and available in its source code, and the long lifetime of the UV-LED (up to 10 000 h) permits a maintenance free application of this device. This simplified device has shown to be able to detect concentrations of aflatoxins of 1 ng, thus offering a cheap and sensitive alternative to currently available TCL scanners. PMID- 11204241 TI - Development of an ex vivo model to investigate the effects of altered haemodynamics on human bypass grafts. AB - The insertion of vein grafts into the arterial circulation may contribute to vessel wall thickening and accelerated atherosclerosis, a common feature of late vein graft failure. We aimed to develop a model suitable for investigation of the effects of altered haemodynamics on human saphenous vein following its implantation into the arterial circulation. Segments of human saphenous vein obtained from patients undergoing coronary artery bypass surgery were sutured at each end to PTFE and placed into a flow system. Pressure and flow rates to stimulate the arterial and venous systems were achieved. A theoretical model of the flow chamber was created and computational fluid dynamics software (FLOTRAN, Swanson Analysis Systems) was used to determine the flow profile within the model. In summary, a flow model has been developed to investigate the effect of altered haemodynamics on the molecular and pathological changes that occur in vein grafts incorporated into the arterial circulation. PMID- 11204242 TI - Effects of asymmetric branch flow rates on aerosol deposition in bifurcating airways. AB - Representative double bifurcation airway models with asymmetric branch flow rate ratios, caused by spatially different downstream impedances or a carinal tumour in one branch, have been considered. For steady laminar inhalation of a dilute micron-particle suspension, i.e. 500 < or = Re < or = 2000 and 0.02 < or = St < or = 0.12, air flow fields, aerosol distributions, and wall particle concentrations have been simulated with a user-enhanced finite-volume code and an off-line particle tracking routine. Particle deposition efficiencies are shown for both asymmetric branch flow rate cases, i.e. unobstructed and tumour-induced. PMID- 11204243 TI - Numerical study of unsteady stenosis flow: parametric evaluation of power-law model. AB - Currently the best indicator for surgical treatment of arterio-sclerosis is the degree of stenosis. Although X-ray angiography is currently the standard, cost and morbidity are distinct disadvantages. By modelling stenosis and studying its biofluid mechanics, one can apply its results in the field of arterial disease research. This formed the motivation for this work. A non-Newtonian (power law) incompressible Navier-Stokes (N-S) solver was developed using the method of operator splitting and artificial compressibility. The vehicle used is the computational fluid dynamics (CFD) numerical library FASTFLO. The power-law model developed is then used to do a parametric study of the effect of 'n' on blood flow mechanics where 'n' is the power index that determines the haematocrit of blood. A pulsatile pressure wave over a cardiac cycle of a second was used to simulate transient flow over a hypothetical two-dimensional stenotic geometry. By comparing the different velocity pressure, wall shear stress and viscosity profiles, it has been found when 'n' increases, the vortex formation and peak wall shear stress decreases (magnitudes of < 1.5 Pa). Since the formation of vortices and low oscillatory wall shear stress on the stenotic wall is detrimental to the well-being of the arterial tract, it can therefore be inferred that there might be a relationship between the diseased state of blood (power law) and early genesis of atherosclerosis. However, the conclusion of this paper marks the advent of new research directions in this field of study. PMID- 11204245 TI - Development and evaluation of a two-dimensional electrocutaneous cognitive feedback system for use in paraplegic standing. AB - Fatigue of electrically activated paralysed muscles is a major factor limiting the duration of functional electrical stimulation (FES) supported paraplegic standing. Fatigue can be significantly delayed by changing the posture. Since paralysed individuals are deprived of proprio- and exteroception from the lower limbs they are not aware of the posture and loading of their paralysed legs. If suitable cognitive feedback (CF) information about posture in the sagittal and frontal planes is provided, they might be able to successfully exercise posture switching. A two-dimensional electrocutaneous CF system was developed. Relative limb loading and the location of the weighted centre of pressure were selected as informational variables. Discrete encoding schemes in the form of spatial and frequency codes were employed and the informational signals were divided into three sub-regions. The ability to correctly interpret the CF was investigated using one- and two-dimension tracking tests in three paralysed subjects, each of whom were studied over five consecutive days. All three subjects were able to use the CF in one-dimension tests. Two subjects could do the same also in two dimension tests. The encoding scheme which was developed to communicate the selected biomechanical variables proved to be easily understood and thus appropriate for use in paraplegic standing. PMID- 11204244 TI - Automatic adjustment of biphasic pulse duration in transthoracic defibrillation. AB - Many studies have proven that biphasic defibrillation pulses are more efficient than the damped sinusoid monopolar waveform. Transthoracic resistance was shown to change during the two phases. On the other hand, it was proven that transthoracic resistance plays an important role in the defibrillation process, yielding the current for selected energy or voltage. Pre-shock measurement of the resistance may lead to improved selection. Stabilized current defibrillators are of low stored-to-delivered energy ratio. Therefore, automatic dynamic adjustment of some defibrillator parameters with respect to transthoracic resistance changes seems rational. An approach is known for modifying the pulse duration, in order to deliver a selected energy. A method is proposed here and an experimental defibrillator is developed for dynamic pulse duration adjustment with the purpose of obtaining a desired optimal time-course of the cardiac cell transmembrane potential. PMID- 11204246 TI - How to produce a pulsatile flow with low haemolysis? AB - It is evident that a pulsatile flow is important for blood circulation because the flow pulsatility can reduce the resistance of peripheral vessels. It is difficult, however, to produce a pulsatile flow with an impeller pump, since blood damage will occur when a pulsatile flow is produced. Further investigation has revealed that the main factor for blood damage is turbulence shear, which tears the membranes of red blood cells, resulting in free release of haemoglobin into the plasma, and consequently leads to haemolysis. Therefore, the question for developing a pulsatile impeller blood pump is: how to produce a pulsatile flow with low haemolysis? The authors have successively developed a pulsatile axial pump and a pulsatile centrifugal pump. In the pulsatile axial pump, the impeller reciprocates axially and rotates simultaneously. The reciprocation is driven by a pneumatic device and the rotation by a dc motor. For a pressure of 40 mm Hg pulsatility, about 50 mm axial reciprocating amplitude of the impeller is desirable. In order to reduce the axial amplitude, the pump inlet and the impeller both have cone-shaped heads, and the gap between the impeller and the inlet pipe changes by only 2 mm, that is the impeller reciprocates up to 2 mm and a pressure pulsatility of 40 mm Hg can be produced. As the impeller rotates with a constant speed, low turbulence in the pump may be expected. In the centrifugal pulsatile pump, the impeller changes its rotating speed periodically; the turbulence is reduced by designing an impeller with twisted vanes which enable the blood flow to change its direction rather than its magnitude during the periodic change of the rotating speed. In this way, a pulsatile flow is produced and the turbulence is minimized. Compared to the axial pulsatile pump, the centrifugal pulsatile pump needs only one driver and thus has more application possibilities. The centrifugal pulsatile pump has been used in animal experiments. The pump assisted the circulation of calves for several months without harm to the blood elements and the organ functions of the experimental animal. The experiments demonstrated that the pulsatile impeller pump is the most efficient pump for assisting heart recovery, because it can produce a pulsatile flow like a diaphragm pump and has no back flow as occurs in a non-pulsatile rotary pump; the former reduces the circulatory resistance and the latter increases the diastole pressure in aorta and thus increases the perfusion of coronary arteries of the natural heart. PMID- 11204247 TI - Rotational laxity after anterior cruciate ligament injury by kinematic evaluation of clinical tests. AB - Despite the numerous studies on anterior cruciate ligament biomechanics and clinical tests, some disagreements still exist in the literature on the role of ACL in restraining rotations and which kinematic test after ACL injuries is the most suitable to evaluate this instability. This work analyses the capability of passive clinical and stress tests to detect an ACL state quantifying rotational instability. The study was conducted on animal knees with a new protocol. We found that an internal-external stress test can give a useful indication on the ACL state when used to estimate the side to side differences while varus-valgus laxity and secondary motions in standard kinematic tests did not seem to be affected by ACL injury. The kinematic protocol performed could be used intra operatively to quantify rotations, allowing a more accurate evaluation of knee instability to guide surgical reconstruction and improve its final outcome. PMID- 11204248 TI - Defining T cell receptors which recognise the immunodominant epitope of the gastric autoantigen, the H/K ATPase beta-subunit. AB - We have previously shown that autoimmune gastritis can be elicited in mice by immunisation with the gastric parietal cell H/K ATPase alphabeta heterodimer, and, furthermore, have identified the H/K ATPase beta-subunit epitope, H/Kbeta253 277 as the dominant epitope of the gastric H/K ATPase. Using gastric H/K ATPase immunised mice, here we have generated two T cell hybridomas specific for the H/Kbeta253-277 peptide, namely 4B11.F4.5 and 1E4.C1. Hybridoma 4B11.F4.5 uses Valpha8 and Vbeta8.2 TCR chains and 1E4.C1 uses Valpha9 and V1beta8.3 chains. Although both hybridomas are specific for H/Kbeta253-277, T cell assays using overlapping 14-mers of the 25-mer epitope showed that the two autoreactive TCRs recognise different regions of the 25-mer. The TCR from 1E4.C1 has been used to generate a TCR beta-chain transgenic mouse. >80% of peripheral CD4+ T cells utilise the Vbeta8.3 transgene. As expected, 1E4-TCR beta-chain transgenic mice are susceptible to neonatal thymectomy induced autoimmune gastritis. While none of the 1E4-TCR beta chain transgenic mice spontaneously developed a destructive gastritis, a minority (20%) of the transgenic mice developed a non-invasive and non-destructive gastritis. This suggests that the pathogenic T cells are maintained in a tolerant state in the periphery of the transgenic mice. PMID- 11204249 TI - Sequence analysis of human endogenous retrovirus clone 4-1 in systemic lupus erythematosus. AB - Human endogenous retroviruses (HERV) have emerged as a possible cause of systemic lupus erythematosus (SLE). We previously detected serum antibodies to the gag region of HERV clone 4-1 in patients with SLE, but not in normal volunteers. In the present study, we detected clone 4-1 messenger RNA (mRNA) in peripheral blood mononuclear cells (PBMC) from SLE patients and performed sequence analysis of the cDNA or genomic DNA from clone 4-1 in these patients. Clone 4-1 mRNA was detected in all of the SLE patients tested, although it was not found in normal controls. Sequence analysis of clone 4-1 in these SLE patients revealed inactivation of the stop codons in part of the gag region. In addition, a computer search of current sequence libraries revealed that the clone 4-1 gag genomic DNA from SLE patients was more highly homologous with the clone 4-1 sequence in chromosome 11 from normal individuals when compared with the sequence of clone 4-1 integrated in the other chromosomes. It is possible that transcription of clone 4-1 from chromosome 11 occurs in SLE, and that the stop codon inactivation contributes to the translation of clone 4-1 gag proteins in patients with this disease. PMID- 11204250 TI - Immunoreactivity to various human cytochrome P450 proteins of sera from patients with autoimmune hepatitis, chronic hepatitis B, and chronic hepatitis C. AB - Numerous human Cytochrome P450 enzymes (CYPs) associated with 'phase I' drug metabolism have been identified. Among them, CYP2D6 is thought to be the major target autoantigen to anti-liver kidney microsome (LKM)-1 autoantibody, a characteristic feature of autoimmune hepatitis (AIH) type II. In this study, we were able to clone CYP2D6 cDNA from a human liver cDNA library and express the CYP2D6 recombinant protein, and also to prepare four other representative human CYP proteins (CYP1A2, 2C9, 2E1, and 3A4). These preparations were used to assay the immunoreactivity of patients with AIH type I (n=35) and type II (n=9). As comparison groups, sera from patients with chronic hepatitis B (n=15), chronic hepatitis C (n=55; 24 anti-LKM-1-positive, 31 anti-LKM-1-negative), and from normal controls (n=30) were included. The five CYP proteins did not react with sera from normal controls nor from patients with chronic hepatitis B. CYP2D6 reacted with sera from 100% (9/9) of AIH type II patients, 79% (19/24) of patients with anti-LKM-1-positive chronic hepatitis C, and 6.5% (2/31) of patients with anti-LKM-1-negative chronic hepatitis C. In contrast, CYP1A2 reacted with serum from one patient with AIH type I, CYP2E1 reacted with sera from two patients with AIH type I, one patient with anti-LKM-1-positive chronic hepatitis C, and two patients with anti-LKM-1-negative chronic hepatitis C, and CYP3A4 reacted with sera from one patient with AIH type II and one patient with anti-LKM-1-positive chronic hepatitis C. CYP2C9 did not react with any of the sera included in this study. From these results, it is suggested that CYPs other than CYP2D6 can function as immunotargets in certain disease conditions. PMID- 11204252 TI - A possible pathogenic role of CD8+ T cells and their derived cytokine, IL-16, in SLE. AB - Current investigations into the role of CD8+ T cells and their derived cytokine, interleukin (IL)-16, in the induction of CD4+ T cell abnormalities in systemic lupus erythematosus (SLE) were reviewed and discussed on the basis of results mainly obtained in our laboratory. PMID- 11204251 TI - Analysis of chromosome 6q in Basque families with type 1 diabetes. GEPV-N. Basque Navarre Endocrinology and Paediatric Group. AB - Over the last few years several studies of linkage between non-HLA loci and type 1 diabetes mellitus have mapped several putative susceptibility genes on chromosome 6q; in fact, positive evidence of linkage and/or association of IDDM5 (6q25), IDDM8 (6q27) and IDDM15 (6q21) with type 1 diabetes has been reported. We have studied these loci in diabetic families of Basque origin, a genetically homogeneous population, to avoid artifactual association results due to admixture within the sample analysed. Statistical analyses of linkage were performed using a transmission disequilibrium test (TDT). We could not confirm linkage for IDDM5, IDDM8 and IDDM15 in our population, possibly due to population-specific differences in genetic susceptibility and/or environmental triggering factors to type 1 diabetes. PMID- 11204253 TI - CD30:CD30 ligand interactions in the immune response. PMID- 11204254 TI - Enhanced mutational activity and disturbed selection of mutations in V(H) gene rearrangements in a patient with systemic lupus erythematosus. AB - To determine the impact of somatic hypermutation and selective influences on the V(H) gene repertoire in SLE, the mutational frequency and pattern of mutations in nonproductively and productively rearranged V(H) genes obtained from genomic DNA of individual CD19+ B cells were analyzed in a patient with SLE. The mutational frequencies of nonproductive (6.54 x 10(-2)) as well as of productive (4.38 x 10( 2)) V(H) rearrangements were significantly higher in the SLE patient than in normal controls (3.8 x 10(-2), p<0.001 and 3.3 x 10(-2); p<0.001, respectively). Analysis of nonproductive rearrangements documented only minor abnormalities of the targeting of the mutator in the SLE patient. The majority of "mutational hot spots", although different than in normals, appeared in the CDRs and an increased frequency of mutations in RGYW/WRCY sequences was observed. Moreover, no biases in base pair changes were found in the nonproductive repertoire. In contrast, there was a selection against A and T mutations and towards G mutations within the productive repertoire. Importantly, there were no significant differences in the R/S ratios of mutations within the FRs between the nonproductive and productive repertoire consistent with abnormalities in elimination of B cells expressing V(H) genes with these mutations. The result of this abnormality was a significantly higher R/S ratio of the V(H)genes in the productive repertoire of the SLE patient compared to normals (p<0.05). These data indicate that the mutational machinery was markedly enhanced in this SLE patient but exhibited nearly normal targeting, whereas selective influences were abnormal. These findings suggest that both enhanced mutational activity and disturbances in selection may have played a role in the emergence of autoreactivity in this SLE patient. PMID- 11204255 TI - Balanitis xerotica obliterans--a review. AB - Balanitis xerotica obliterans (BXO) is a scarcely known disease, wrongly considered rare. With a high degree of suspicion and histologic examination, the condition will prove to be much more frequent than one generally believes. The etiology of the condition is unknown at present. Many cases of BXO occurring after circumcision may be cases of secondary phimosis due to BXO not being recognized at the time of surgery. Most of the cases of BXO are seen in the third to fifth decades of life, even though they may occur at the extremes of age. Biopsy of the lesions is not essential in all cases and is indicated to differentiate from penile cancer and in atypical cases. Early diagnosis and treatment of BXO are very important in preventing the urological complications of the diseases such as urethral stricture. Treatment of BXO depends on the anatomic location of the lesions and their extent and severity, together with the rapidity of progression of the disease process. The treatment may vary from topical corticosteroids, laser vaporization in early cases to meatoplasty and urethroplasty in extensive cases. Topical pharmacotherapy is useful in the early stages to reduce the initial symptoms and slow down the progression, but is not effective in all cases and is not the curative treatment of disease. Meatal stenosis, phimosis, scar adhesions, fissures, erosions of glans and prepuce and involvement of the urethra are indications for surgical treatment. Surgery seems to be the only treatment that can relieve the symptoms of advanced disease. Modified circumcision, with total removal of inner preputial layer, definitively relieves phimosis without any recurrence. Meatotomy will not prevent the recurrence of meatal stenosis. Excision of the scleroatrophic tract and grafting of the glans base, coronal sulcus, and the end of the shaft give a complete relief of pain during erection and intercourse in circumcised patients with balanopreputial adhesions and restore the elasticity of the skin of penile shaft. These procedures have been shown to yield excellent functional results during a follow-up period of up to 4 years. BXO involving anterior urethra can be treated by 2-stage urethroplasty or substitution urethroplasty. The complete excision of the stricture and flap urethroplasty seems to be better than a 2-stage procedure. However, at the present time, it is not possible to say that surgery can completely resolve this chronic and progressive disease. Despite many reports in the literature of cases of BXO associated with squamous cell carcinoma, the etiologic relationship between the two conditions is uncertain. PMID- 11204256 TI - Suramin administration is associated with a decrease in serum calcium levels. AB - Suramin has been shown to have an effect on bone resorption in in vitro models. It is not clear if a similar effect is seen in patients treated with suramin. The clinical effect of suramin treatment on total serum calcium was examined in two groups of patients with hormone-refractory prostate cancer. In all, 28 patients in group 1 were examined within 2 weeks before and 2 weeks after suramin treatment and 72 patients in group 2 were examined within 2 weeks before, during, and after treatment with suramin. In addition, calcium controls spiked with suramin were run in three different commercially available assays for evaluation of the effect of suramin dose on calcium determination. Group 1 patients showed a decrease in serum calcium after treatment with suramin. The mean uncorrected serum calcium level was 2.29 +/- 0.025 mmol/l before treatment and 2.09 +/- 0.025 mmol/l after treatment (P < 0.0001, paired Wilcoxon test). The mean serum calcium value corrected for albumin was 2.33 +/- 0.02 mmol/l before treatment and 2.24 +/ 0.02 mmol/l after treatment (P = 0.0022, paired Wilcoxon test). Group 2 patients also displayed a decrease in serum calcium after treatment with suramin. The mean baseline value was 2.23 mmol/l (median 2.26 mmol/l, range 1.20-2.54 mmol/l). The mean level of serum calcium corrected for albumin as determined at the end of treatment was 2.14 mmol/l (median 2.16 mmol/l, range 0.98 2.46 mmol/l). In all, 48 patients for whom pre- and post-treatment values were available for analysis displayed a median calcium decrease of 0.09 mmol/l (P = 0.0005, Wilcoxon signed rank test for the null hypothesis of no change). For 68 patients in group 2, data on serial serum calcium measurements during treatment were available for analysis. A projected median decrease in serum calcium of 0.06 mmol/l (range 0.43 to 0.72 mmol/l) over an 8-week interval of suramin therapy was found. Overall, 47 of the 68 slopes were negative (P = 0.0022, Wilcoxon signed-rank test). Nine patients were treated with suramin for less than 6 weeks. These patients' calcium levels were significantly higher than those of 50 patients treated for longer periods (median value 2.24 versus 2.16 mmol/l, P = 0.035, Wilcoxon rank-sum test). No correlation was found between suramin dose and calcium level using the Kodak Ektachem, Hitachi 914, or Synchron Clinical System CX3 method. In conclusion, suramin treatment was consistently associated with decreases in serum calcium in two groups of patients with hormone-refractory cancer. Suramin placed in calcium controls did not affect calcium determination using three commercially available methods. PMID- 11204257 TI - Intermittent androgen deprivation (IAD) in patients with biochemical failure after radical retropubic prostatectomy (RRP) for clinically localized prostate cancer. AB - We report a study in which our objective was to analyze the clinical response during IAD in patients with biochemical failure after RRP for clinically localized prostate cancer. Between February 1994 and May 1996, 34 patients who exhibited a primary postoperative decrease in PSA to below the detection limit after RRP and then showed PSA progression during follow-up were included as group 1 and 17 patients in whom PSA did not decrease after RRP were included as group 2. Patients were offered IAD when PSA progressed over 0.4 ng/ml in group 1 and over 4.0 ng/ml in group 2. Median follow-up is 184 weeks in group 1 and 206 weeks in group 2. The median time "off" therapy increased from 25% (1st cycle) to 68.7% (5th cycle) of the entire cycle in group 1 and from 33.3% to 58.3% in group 2. Nine out of 12 cases with Gleason score > or =8 failed to respond to IAD and all developed metastatic and/or local failure. No case with Gleason score <7 failed to respond to IAD. Our conclusions suggest that IAD may be effective in patients with biochemical progression after RRP. In our experience, Gleason score seems to be an important variable. PMID- 11204258 TI - Clinical application of NMP22 and urinary cytology in patients with hematuria or a history of urothelial carcinoma. AB - For evaluation of the clinical application of immunoassay for nuclear matrix protein 22 (NMP22 immunoassay) and urinary cytology for early diagnosis and detection of bladder cancer in patients with hematuria and/or a previous history of bladder cancer, 209 urine samples obtained from 137 patients presenting episodes of hematuria or a history of bladder cancer were assayed for NMP22 levels and/or prepared for cytology examination. Biopsy was performed when any visible tumor was identified during cystoscopy examination. The median NMP22 concentrations measured in samples taken from patients with active bladder cancer, from patients with a history of bladder cancer but no active disease, from patients with hematuria, and from healthy volunteers were 18.95, 5.45, 6.39, and 3.75 U/ml, respectively. The urinary NMP22 level recorded for patients with urothelial carcinoma was significantly higher than that noted for individuals without active disease. The sensitivity of the NMP22 assay and of urinary cytology in diagnosing bladder cancer was 69% and 67%, respectively. In contrast, the specificity of these two diagnostic modalities reached 72% and 93%, respectively. The NMP22 assay is slightly more sensitive but less specific than urinary cytology in detecting bladder cancer. This study indicates that determination of urinary NMP22 levels is a useful and noninvasive tool for the detection of bladder cancer because of its high sensitivity. The urinary NMP22 assay may be used as a first-line routine screening method; however, it cannot replace the use of urinary cytology because of its lower specificity. PMID- 11204259 TI - Prostatic expression of human 5alpha-reductase type 2 during finasteride therapy: a randomized, double-blind, placebo-controlled study. AB - This study was aimed at exploring the effect of finasteride, a non-steroidal competitive inhibitor of the enzyme 5alpha-reductase, on 5alpha-reductase type 2 at the mRNA level in human prostate, using an in situ hybridization technique. After randomization, 10 men with benign prostatic hyperplasia (BPH) received oral finasteride (5 mg daily) and five men with BPH received placebo daily. Careful clinical examination was carried out and 2 biopsy samples were taken transrectally before the treatment and after 3, 6, and 12 months of treatment. In situ hybridization was carried out and expression of 5alpha-reductase type 2 mRNA was measured. The results showed that finasteride treatment had no permanent effect on expression of 5alpha-reductase type 2 in prostatic epithelium, compared with placebo treatment. Expression varied during treatment, but there was no clear tendency in this expression. The signal was localized in the epithelial cells. We conclude that finasteride treatment had no clear effect on human 5alpha reductase type 2 expression in the prostate. PMID- 11204260 TI - Quality of micturition in male patients with orthotopic neobladder replacement. AB - We evaluated the quality of micturition in patients with orthotopic neobladder replacement. In the present study, 58 patients who had undergone orthotopic neobladder replacement following cystectomy were enrolled. The quality of micturition was evaluated by means of uroflowmetry, a self-administered questionnaire and a 24-h frequency-volume chart. The questionnaire consisted of 26 questions concerning storage (9 questions), evacuation of urine (9), patient's satisfaction with neobladder (3), limitations in daily life (3) and pain (2). In addition, 11 of the questions were followed immediately by a question concerning inconvenience to the patients. The mean follow-up period was 35 months (range 6 80). On uroflowmetry, the mean peak flow rate was 13.5 ml/s with a low average flow rate (mean: 5.7 ml/s), and the voiding time was considerably prolonged (mean: 70.2 s). According to the frequency-volume chart and questionnaire responses, although the frequency and tidal volume of micturition were normal, the majority of patients were conscious of retarded, intermittent, prolonged, and weak stream and of straining during voiding. Diurnal or nocturnal incontinence was noticed subjectively in as many as 69% of the patients. However, the degree of urine leakage was minimal. In spite of the fact that 66% of the patients replied that their micturition status was worse than before surgery and that 69% of the patients felt dissatisfied, the degree of inconvenience was low in every item and the limitations in daily life were minimal. Although micturition in patients with neobladder replacement appeared to be of lower quality than that in normal subjects and was considered by many to be unsatisfactory, most patients were able to adjust themselves to it without significant inconvenience. PMID- 11204261 TI - Improvement of health outcomes after continued implementation of a clinical pathway for radical nephrectomy. AB - The clinical pathway is an important tool for outcome management. We evaluated the overall effects of the continued implementation of a clinical pathway for radical nephrectomy on the length of hospital stay, admission charges, and the quality of medical care. The data obtained from the second-year implementation (group 3) of the clinical pathway were compared with the data from the first-year implementation (group 2) and the year preceding implementation (group 1). Thirty seven consecutive patients with renal cell carcinoma underwent radical nephrectomy in group 1, 47 in group 2, and 55 in group 3; all were enrolled in this study. The length of hospital stay, average admission charges, and 8 quality indicators were measured in these patients. We also evaluated the variances in the implementation of the clinical pathway. The mean length of stay decreased by 14.0% (P = 0.0048) in group 2, and by 15.8% (P= 0.0014) in group 3, when compared to group 1. The total admission charges significantly decreased by 19.0% (P = 0.001) in group 2, and by 27.9% (P < 0.0001) in group 3, compared to the charges for group 1. A continued decrease in charges for operation and anesthesia, laboratory, pharmacy, and others were found 2 years after implementation of the clinical pathway. Among the 8 quality indicators, 2 were continuously improved in the second-year implementation of the clinical pathway, 2 were improved significantly in the second-year implementation only, and 4 showed no significant change at all. Variances from the clinical pathway decreased significantly after continued implementation. Continued implementation of the clinical pathway for radical nephrectomy can improve a physician's practice continuously by decreasing the length of hospital stay, admission charges, and variances, and by improving quality. However, the improved results after implementation of the clinical pathway should be maintained carefully to assure good health care. PMID- 11204262 TI - Inhibition of uropathogenic biofilm growth on silicone rubber in human urine by lactobacilli--a teleologic approach. AB - The ability of three Lactobacillus strains to inhibit the adhesion and growth of naturally occurring uropathogens on silicone rubber was investigated in human urine. The importance of biosurfactant production by Lactobacillus in discouraging uropathogen growth was determined in relation to the binding affinities of the lactobacilli for silicone rubber. L. fermentum B54 markedly inhibited uropathogen growth on the silicone rubber disks after 8 days for all five men included in the study, albeit to various extents ranging from 77% to 100%. In urine from women, however, this inhibition was less clear, as it was absent for two of the four women participating in this study. L. casei rhamnosus 36 completely discouraged uropathogen growth on the disks after 8 days for three of the four women, whereas its effect in urine from men was less pronounced (inhibition ranged from 48% to 100% and was absent for one man). L. casei rhamnosus ATCC 7469T was the least inhibitory Lactobacillus strain tested and inhibition was absent for a number of both male and female participants, possibly as a result of the low binding affinity of this strain for silicone rubber and of its inability to release biosurfactants. We conclude that the inhibition of uropathogen growth is dependent on the Lactobacillus strain involved, and for L. fermentum B54 it was demonstrated to be sex-related. Hence, inhibition must be considered a multifactorial process. PMID- 11204263 TI - Hemodynamic insult by vascular risk factors and pharmacologic erection in men with erectile dysfunction: Doppler sonography study. AB - To evaluate the penodynamic impact of known vascular risk factors in men with erectile dysfunction, we obtained thorough medical histories covering diabetes, hypertension, heart disease and hypercholesterolemia, alcohol ingestion, and smoking in 265 consecutive patients. We also measured their penile hemodynamic parameters by color duplex ultrasonography after intracavernous prostaglandin E1 injection. In patients with vascular risk factors there was a statistically significant decrease in the peak systolic velocity and increase in the end diastolic velocity of the cavernosal artery (P < 0.01). Those men who had diabetes had higher average end-diastolic velocities and lower resistance indices (P < 0.01). Smoking and alcohol use also affected penile hemodynamics (P < 0.05). These data confirm that vascular risk factors do increase the likelihood of vasculogenic impotence and that diabetes plays a major role in veno-occlusive dysfunction in the penis. PMID- 11204264 TI - Pilot study of the transdermal application of testosterone gel to the penile skin for the treatment of hypogonadotropic men with erectile dysfunction. AB - Androgens influence important central and peripheral mechanisms of the erectile system. The relevance of a moderate decrease of serum testosterone level for erectile dysfunction (ED) has not been clarified so far. The aim of our study was to offer an easy transcutaneous method of androgen application. A previous study on the pharmacokinetic profile of the testosterone gel applied, showed marked elevation of the serum levels of testosterone. In our study, 46 hypogonadal patients with ED and total lack of vaginal penetration applied testosterone gel (4 mg/day; supplied by Azupharma, Germany) to the penile skin twice a day over 6 8 weeks, after a run-in period with placebo gel of 2 weeks. All patients showed decreased testosterone serum levels (<3 ng/ml) in at least two morning samples over a period of 3 weeks before treatment. Psychogenic etiology was excluded by a sexual psychologist. Patient age was 37-69 years (mean 53.5). Three patients (6.5%) responded to placebo in the run-in phase and were withdrawn from further treatment. Fifteen patients (32.6%) showed improved erection, allowing penetration and sexual intercourse. Twenty-eight patients (60.9%) did not respond to therapy. Local genital skin irritation was not observed. Elevation of peripheral testosterone was not correlated to a positive therapy response. A success-rate of 32.6% in this group of patients after exclusion of psychogenic patients and placebo-responders seems to justify further investigations. A medication period of 6-8 weeks is most probably too short to induce imaginable regenerative effects of testosterone on the erectile system. We therefore suggest that future double-blind and placebo-controlled studies should be designed for a minimum of 3 months. Testosterone gel may be a cost effective form of androgen administration. PMID- 11204265 TI - 1999 rerun of the 1996 German Urinary Incontinence Survey: will doctors ever ask? AB - The German Incontinence Relief Society and supporting companies have been conducting numerous urinary incontinence awareness and continuing medical education campaigns. However, comparison of results from an epidemiologic survey involving 6,607 over-50-year-old patients in 1996 and a similar investigation among 6,481 patients in the same age group in 1999 reveals that German physicians are now even less likely to address this taboo subject, thus withholding appropriate care from incontinent patients. Possible reasons for this alarming development include the financial restraints imposed on German doctors in private practice and a lack of appreciation of the problems associated with incontinence among health policymakers. PMID- 11204267 TI - Diagnosis and management of incidental ureterocele during the treatment of clinically localized prostate cancer. AB - Two instances of simultaneous diagnosis of prostate cancer and ureterocele were recently identified. In one patient an ectopic ureterocele in a duplex system with an obstructed upper pole was unroofed at the time of radical prostatectomy. Surgical excision of the ureterocele wall provided decompression of the obstructed system. In a second patient, bilateral intravesical ureteroceles associated with normal renal units were left untreated. Complications were not associated with the untreated ureteroceles. On rare occasions a ureterocele may be discovered incidentally during the evaluation of patients with prostate cancer. When radical prostatectomy is planned, treatment of the ureteroceles should be determined by the ureterocele's size, anatomic configuration, and location and by the degree of obstruction of the affected renal unit. Surgical excision of the ureterocele at the time of radical prostatectomy may be the best approach for patients requiring treatment. PMID- 11204266 TI - Initial clinical experience with the selective phosphodiesterase-I isoenzyme inhibitor vinpocetine in the treatment of urge incontinence and low compliance bladder. AB - Current pharmacological treatment modalities for urge incontinence and low compliance bladder are limited by a low clinical efficacy and the significant side effects of the standard drugs available. Previous in vitro studies indicated a possible functional relevance of the intracellular phosphodiesterase (PDE)-1 isoenzyme in the regulation of human detrusor smooth muscle contractility. We therefore investigated the effect of the PDE-1 inhibitor vinpocetine in nonresponders to standard pharmacological therapy. In 11/19 patients (57.9%) clinical symptoms and/or urodynamic parameters were improved. Although these initial data are preliminary, they represent the first evidence that isoenzyme selective PDE inhibition may be a novel approach to the treatment of lower urinary tract disorders. PMID- 11204268 TI - Synchronus renal cell carcinoma and Bellini duct carcinoma: a case report on a rare coincidence. AB - Bellini duct carcinoma or collecting duct carcinoma (CDC) is a rare but aggressive primary renal neoplasm. The coexistence of two synchronous neoplasms in the same kidney is highly infrequent. As a result, it is hardly surprising that there are no references to renal cell carcinoma (RCC) combined with CDC of the same kidney in the literature. Histology and immunohistochemistry are important tools for differentiating between the two types of tumors involved. We present the first case of a synchronous occurrence of RCC and CDC of the same kidney. PMID- 11204269 TI - Endocytosis of uncleaved tumor necrosis factor-alpha in macrophages. AB - Activated monocytes and macrophages secrete the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). TNF-alpha is produced as a 26 kd transmembrane protein that is cleaved to release a 17 kd soluble protein. TNF-alpha in both forms is biologically active. The intracellular trafficking of membrane associated TNF-alpha in lipopolysaccharide-activated mouse macrophages was assessed after treatment with the metalloprotease inhibitor BB-3103, which prevents the cleavage of pro-TNF-alpha. Immunoprecipitation and immunofluorescence studies showed sustained expression of cell-associated TNF alpha in the presence of the inhibitor. Cell immunoreactivity and surface biotinylation revealed that uncleaved TNF-alpha accumulated on the cell surface and was endocytosed, appearing in intracellular vesicles. Perturbation of post Golgi traffic blocked the surface expression of 26 kd TNF-alpha. Tracking a bolus of TNF-alpha over time in cycloheximide-treated cells confirmed that uncleaved TNF-alpha is first transported to the cell surface and subsequently endocytosed. Vesicular structures immunoreactive for TNF-alpha were identified as endosomes by double labeling. The secretory and membrane-associated endocytic trafficking of TNF-alpha provides a mechanism for modulating the quantity of biologically active 26 kd TNF-alpha expressed on macrophages, allowing regulation of paracrine and autocrine responses. PMID- 11204270 TI - Cell lineage analysis during liver development using the spf(ash)-heterozygous mouse. AB - Biliary epithelial cells differentiate from periportal hepatoblasts during fetal mouse liver development. It remains to be determined whether each hepatoblast is equivalent for differentiation into hepatocytes and biliary epithelial cells in normal liver development. To resolve this question, the mosaic pattern of ornithine transcarbamylase (OTC) expression was analyzed in the hepatoblast population of spf(ash) (sparse-fur with abnormal skin and hair)-heterozygous fetal mouse livers, in which random inactivation of either the X chromosome carrying the spf(ash) gene (causing OTC deficiency) or its wild-type gene occurs. Aggregates (patches) of OTC-positive hepatoblasts showed very complex patterns, and their shapes and size distributions were similar in sections from periportal regions and nonperiportal regions of the fetal liver in which bile duct differentiation by periportal hepatoblasts occurred. Average sizes of periportal patches were larger than those of nonperiportal patches because of the presence of more hemopoietic cells in the latter region. The OTC mosaicism in periportal bile duct progenitors and hepatoblast islands of other liver parenchyma was also similar. These results suggest that the growth patterns of hepatoblasts are similar in both periportal and nonperiportal regions. Isolated three-dimensional patches comprising hepatoblasts giving rise to only biliary epithelial cells or hepatoblasts giving rise to both hepatocytes and biliary epithelial cells were observed in periportal regions. In nonperiportal regions, patches consisting of hepatoblasts differentiating into hepatocytes were also seen. Thus, it is likely that there are three lineages for the developmental fates of hepatoblasts: hepatoblasts giving rise to only biliary epithelial cells, hepatoblasts giving rise to only hepatocytes, and hepatoblasts giving rise to both of them. PMID- 11204272 TI - Expression of nitric oxide synthases and nitrotyrosine during blood-brain barrier breakdown and repair after cold injury. AB - This study was undertaken to determine whether the blood-brain barrier (BBB) breakdown and cerebral edema occurring post-trauma are associated with overexpression of the endothelial (e) and inducible (i) nitric oxide synthases (NOS), enzymes responsible for nitric oxide (NO) biosynthesis. These enzymes were determined quantitatively at the mRNA level and qualitatively at the protein level in the rat cerebral cortical cold injury model, during a period up to 6 days post-injury. In addition, peroxynitrite generation at the lesion site was detected by immunolocalization of nitrotyrosine as a marker of NO-superoxide interactions. These studies were correlated with the permeability status of the BBB by immunohistochemical detection of endogenous fibronectin extravasation in the same brains. BBB breakdown was immediate in lesion vessels, it was present as early as 10 minutes post-lesion and delayed in perilesional vessels that showed maximal BBB breakdown between 2-4 days. The BBB was restored to normal at 6 days post-lesion. An increase in both eNOS and iNOS mRNA was observed at the lesion site as compared with the contralateral hemisphere at 12 hours, 2 days, and 4 days. The mRNA returned to resting levels by 6 days. Increased eNOS protein was observed in the endothelium of permeable perilesional vessels and neovessels and in the endothelium of the hyperplastic pial vessels overlying the lesion site. iNOS protein was observed initially in polymorphonuclear leukocytes at the lesion site and later in macrophages, endothelial cells, and the smooth muscle cells of the overlying pial vessels. Furthermore, nitrotyrosine was demonstrated at the lesion site up to 5 days. Up-regulation of the NO synthases at both the mRNA and protein level accompanied by presence of nitrotyrosine during BBB breakdown and angiogenesis suggests that NO has a role in the pathogenesis of these processes. PMID- 11204271 TI - Cell invasion is affected by differential expression of the urokinase plasminogen activator/urokinase plasminogen activator receptor system in muscle satellite cells from normal and dystrophic patients. AB - The aim of this study was to evaluate the differential expression and the function in cell movement and proliferation of the urokinase plasminogen activator (u-PA) system in muscle satellite cells (MSC) of normal individuals and patients with Duchenne muscular dystrophy (DMD). By immunoenzymatic, zymographic, and radioligand binding methods and by quantitative polymerase chain reaction of the specific mRNA we have shown that both normal and DMD MSC produce u-PA and the plasminogen activator inhibitor-1 and express u-PA receptors (u-PAR). During the proliferation phase of their growth-differentiation program, MSC from DMD patients show more u-PAR than their normal counterpart, produce more plasminogen activator inhibitor-1, and release low amounts of u-PA into the culture medium. By Boyden chamber Matrigel invasion assays we have shown that normal MSC are more prone than DMD cells to spontaneous invasion but, when subjected to a chemotactic gradient of u-PA, DMD MSC sense the ligand much better and to a greater extent than normal MSC. u-PA also stimulates proliferation of MSC, but no difference is observable between normal and DMD patients. Antagonization of u-PA/u-PAR interaction with specific anti-u-PA and anti-u-PAR monoclonal antibodies and with antisense oligonucleotides inhibiting u-PAR expression indicates that u-PA/u-PAR interaction is required in spontaneous and u-PA-induced invasion, as well as in u PA-induced proliferation. PMID- 11204273 TI - Effect of angiogenic and antiangiogenic compounds on the outgrowth of capillary structures from fetal mouse bone explants. AB - Fetal mouse metatarsals are well-known models to study cartilage differentiation and osteoclastic resorption. We show here the outgrowth of PECAM-1 positive tubelike structures from the bone rudiments. This feature can be used to study angiogenesis in vitro. The area of outgrowth significantly increased with culture time, as shown by computerized image analysis of PECAM-1 positive tubelike structures. Treatment with recombinant human vascular endothelial growth factor (rhVEGF-A) stimulated the formation of tubelike structures. Treatment of explants with the angiogenesis inhibitor endostatin, the chemokine IP-10, and the thalidomide derivative phatolyl glutamic acid (PG-acid) resulted in an inhibition of the formation of PECAM-1 positive tubelike structures of 48.8% (+/- 4%), 50.2% (+/- 12%), and 80.8% (+/- 3%), respectively. Outgrowth of tubelike structures was partly dependent on endogenous VEGF-A because treatment with anti-mVEGF-A and truncated VEGF receptor 1 (soluble fms-like tyrosine kinase 1, sFIt1) strongly inhibited the formation of tubelike structures 74% (+/- 4%) and 38% (+/- 5%), respectively. Neither onset of tube formation nor total area of tubelike structures were changed when metatarsals were cultured on a fibrin gel or collagen type I gel. Tube formation required activation of matrix metalloproteinases because treatment of the bones with an inhibitor of matrix metalloproteinases completely inhibited migration and tube formation, whereas treatment with an inhibitor of plasmin had no effect. In conclusion, we describe a new in vitro model to study angiogenesis that can be used to test the angiogenic or antiangiogenic potential of novel test compounds that also combines the multicellularity of in vivo assays with the accessibility and flexibility of in vitro assays. PMID- 11204274 TI - Variations of proline-rich kinase Pyk2 expression correlate with prostate cancer progression. AB - Proline-rich kinase 2 (Pyk2), also known as CAKbeta (cell adhesion kinase beta), is a cytoplasmic tyrosine kinase that is structurally related to focal adhesion kinase. Pyk2 is expressed in different cell types including brain cells, fibroblasts, platelets, and other hemopoietic cells. Pyk2 is rapidly tyrosine phosphorylated in response to diverse extracellular signals acting via different post receptor pathways. We have investigated whether this protein kinase is functionally expressed in normal and neoplastic prostate tissues. In this study, we demonstrate that Pyk2 is expressed only in normal epithelial prostate tissue and in benign prostatic hyperplasia, whereas its expression progressively declines with an increasing grade of malignancy of prostate cancer. PMID- 11204275 TI - Fibroblast growth factor 2 activation of stromal cell vascular endothelial growth factor expression and angiogenesis. AB - Angiogenesis is a key component of human cancer progression and metastasis. In an effort to recapitulate early events in tumor-induced angiogenesis, we have employed a subcutaneous Matrigel implant model using immunodeficient mice as hosts. Matrigel-containing fibroblast growth factor 2 (FGF-2; 1.2 microg/ml) induced stromal cell infiltration into the Matrigel/skin interface within 4 days and maximal neovascularization at 7 days. Cells staining positive for the endothelial cell marker, platelet-endothelial cell adhesion molecule 1 (PECAM-1), were present in neovessels and in isolated cells within the Matrigel matrix. Immunohistochemical analysis revealed high levels of vascular endothelial growth factor (VEGF) deposited in the stromal interface present only in the FGF-2 containing but not in control Matrigel implants. VEGF expression was confirmed with in situ hybridization. High VEGF mRNA levels were observed in the infiltrating stromal cells but not in endothelial or endothelial precursors as defined by PECAM-1 staining. In vitro analysis of FGF-2-treated embryonic fibroblasts, Balb/c 3T3 cells, showed an induction of VEGF transcription, mRNA synthesis, and protein secretion as defined by transcriptional reporter, Northern blot, and ELISA assays. The FGF-2-induced VEGF expression was not dependent on select matrix adherence or signaling components because VEGF mRNA expression induced by FGF-2 was equally activated on serum, basement membrane, and fibronectin matrix substrates. Systemic application of anti-VEGF antibodies significantly repressed FGF-2-induced angiogenesis over control antibody by 88% (p < 0.001). These data support an FGF-2 angiogenic model that is dependent on endothelial cell activation, stromal cell infiltration, and VEGF expression by the infiltrating stromal cell population. PMID- 11204276 TI - Promoter hypermethylation of the RB1 gene in glioblastomas. AB - Loss of expression of the retinoblastoma gene (RB1) has been shown to occur in up to 25% of glioblastomas (WHO Grade IV). To elucidate the underlying mechanism, we assessed RB1 promoter hypermethylation using methylation-specific polymerase chain reaction and RB1 expression by immunohistochemistry in 35 primary (de novo) glioblastomas and in 21 secondary glioblastomas that had progressed from low grade diffuse astrocytoma (WHO Grade II) or anaplastic astrocytoma (WHO Grade III). Promoter hypermethylation was significantly more frequent in secondary (9 of 21, 43%) than in primary glioblastomas (5 of 35, 14%; p = 0.0258). There was a clear correlation between loss of RB1 expression and promoter hypermethylation. In the majority of glioblastomas with loss of RB1 expression, there was promoter hypermethylation (11 of 13, 85%), whereas 93% of tumors with RB1 expression had a normal RB1 gene status (p < 0.0001). In three glioblastomas, areas with and without RB1 expression were microdissected; promoter hypermethylation was detected only in areas lacking RB1 expression. In patients with multiple biopsies, methylation of the RB1 promoter was not detectable in the less malignant precursor lesions, ie, low-grade diffuse and anaplastic astrocytoma. These results indicate that promoter hypermethylation is a late event during astrocytoma progression and is the major mechanism underlying loss of RB1 expression in glioblastomas. PMID- 11204277 TI - Localization of tissue transglutaminase in human carotid and coronary artery atherosclerosis: implications for plaque stability and progression. AB - Although atherosclerosis progresses in an indolent state for decades, the rupture of plaques creates acute ischemic syndromes that may culminate in myocardial infarction and stroke. Mechanical forces and matrix metalloproteinase activity initiate plaque rupture, whereas tissue inhibitors of metalloproteinases have an important (albeit indirect) role in plaque stabilization. In this paper, an enzyme that could directly stabilize the plaque is described. Tissue transglutaminase (TG) catalyzes the formation of epsilon(gamma-glutamyl)lysine isopeptide bonds that are resistant to enzymatic, mechanical, and chemical degradation. We performed immunohistochemistry for TG in atherosclerotic human coronary and carotid arteries. TG was most prominent along the luminal endothelium and in the medium of the vessels with a distribution mirroring that of smooth muscle cells. Variable, often prominent, immunoreactivity for TG was also seen in the intima, especially in regions with significant neovascularization. Additionally, TG was detected in fibrous caps and near the "shoulder regions" of some plaques. A monoclonal antibody to the transglutaminase product epsilon(gamma-glutamyl)lysine isopeptide demonstrated co-localization with TG antigen. Transglutaminase activity was found in 6 of 14 coronary artery atherectomy samples. Cross-linking of TG substrates such as fibrinogen, fibronectin, vitronectin, collagen type I, and protease inhibitors stabilized the plaque. Furthermore, the activation of transforming growth factor-beta-1 by TG might be an additional mechanism for the promotion of plaque stabilization and progression by increasing the synthesis of extracellular matrix components. PMID- 11204278 TI - Fas-induced apoptosis is a rare event in Sjogren's syndrome. AB - The aim of this study was to perform a controlled in situ analysis on the incidence of apoptosis, investigate the expression of apoptosis-mediating proteins, and determine the frequency of apoptotic CD4+ and CD8+ T cells in Sjogren's syndrome (SS). The study was extended to patients with atrophy-fibrosis (AF) not related to SS, as well as to a control group. Immunohistochemistry and the terminal deoxynucleotidyl transferase mediated dUTP digoxigenin nick end labeling (TUNEL) method were applied to study the Fas and FasL expression and the incidence of apoptosis in salivary glands (SG) from patients with primary and secondary SS, AF, and controls. These methods were also combined to enable simultaneous detection of apoptotic and CD4+ or CD8+ T cells. Despite abundant expression of Fas and FasL in SS SG, apoptotic cells were not exceeding 1% in the foci of infiltrating mononuclear cells (IMC). Double staining showed that the frequency of apoptosis was low among both CD4+ and CD8+ T cells. Only a few TUNEL+ epithelial cells were found in all patient groups. Fas was expressed predominantly on SS IMC, single SS epithelial cells, and a few normal acinar cells, but not in AF SG. Although FasL was present on SS and AF IMC and epithelial cells, it was rarely detected in normal tissue. Consequently we demonstrate that Fas-induced apoptosis among SS SG is a rare event. Our findings support an earlier hypothesis indicating that IMC seem to be able to escape apoptosis, resulting in foci of inflammatory cells. Notably, however, no obvious correlation can be drawn to previous studies where a high incidence of apoptosis of epithelial cells was proposed as an important mechanism leading to decreased glandular function, which is a hallmark of SS. PMID- 11204279 TI - Hugo Wolfgang Moser--an excellent "science dealer". PMID- 11204280 TI - X-Linked adrenoleukodystrophy: overview and prognosis as a function of age and brain magnetic resonance imaging abnormality. A study involving 372 patients. AB - The phenotypic expression of X-linked adrenoleukodystrophy (X-ALD) ranges from the rapidly progressive childhood cerebral form to the milder adrenomyeloneuropathy (AMN) in adults. It is not possible to predict phenotype by mutation analysis or biochemical assays. This study reports on 372 patients ranging in age from less than 3 years to adulthood, who have been followed at the Kennedy Krieger Institute. With the aim of determining whether a method could be developed to predict clinical course by analysis of data available at time of first contact, the patients were subdivided into 18 subgroups on the basis of age and the extent of brain magnetic resonance (MRI) abnormality utilizing the MRI scoring system devised by Loes et al. Scores to grade degree of neurologic and neuropsychologic impairment were also developed. There was strong correlation between MRI and the neurology and neuropsychology scores at baseline. Information based exclusively on age and MRI score at time of first contact was highly predictive of future clinical course and should aid the evaluation of the effects of bone marrow transplantation and the selection of patients for this procedure, as well as the evaluation of other therapies that may be developed in the future. PMID- 11204281 TI - Early neurological signs in preterm infants with unilateral intraparenchymal echodensity. AB - The aim of the study was to document the early developmental course of neurological signs in a group of preterm infants at risk for hemiplegia due to unilateral intraparenchymal echodensity (UIPE). Sixteen preterm infants with UIPE and sixteen controls were given serial neurological examinations, according to the protocols currently adopted in the different NICUs of the project. Moreover, the quality assessment of their general movements (GMs) was assessed subsequently from videotapes, from birth until around four months postterm. At two years, 12 of the UIPE infants showed hemiplegia and one suffered from asymmetrical diplegia. The findings of the traditional neurological examination were abnormal for the large majority of the UIPE infants, although normal findings were also recorded in some cases, especially during the preterm period. Asymmetries were found after term age in nine UIPE and in two control infants. From the first observation onwards, all infants with UIPE showed bilaterally abnormal GMs and in those with unfavourable outcome fidgety movements (FMs) were absent. At the FMs period (9-16 weeks postterm), all infants with subsequent hemiplegia showed asymmetry of distal segmental movements which were reduced or absent on the side contralateral to the lesion. CONCLUSIONS: Unilateral brain lesions induce clear neurological signs and abnormal GMs in particular, although these abnormalities are not initially asymmetrical. A reduction of segmental movements on one side of the body during the third month postterm is highly predictive of hemiplegia. PMID- 11204282 TI - Monozygotic twins with fetal akinesia: the importance of clinicopathological work up in predicting risks of recurrence. AB - Fetal Akinesia Deformation Sequence (FADS) or Pena-Shokeir Sequence is a heterogeneous group of disorders in which prolonged decrease or absence of fetal movements results in a series of deformational anomalies: multiple contractures, pulmonary hypoplasia, craniofacial anomalies, polyhydramnios, intrauterine growth retardation, and short umbilical cord. Three sets of monozygotic twins, and their affected sibs, are presented. Detailed pathological work-up established that the two pairs of twins concordant for FADS were of myogenic etiology while the set discordant was due to anoxic-ischemic damage. In the myogenic cases, the rate of recurrence was high, in agreement with the findings from the study on arthrogryposis multiplex congenita of myogenic origin. In light of these findings, in sporadic cases of myogenic FADS, counselling, a recurrence risk of 25% seems prudent. In neurogenic cases associated with primary cerebral malformations, there are cases cited in the literature that are clearly recessive as indicated by affected sibs, but many reported are isolated occurrences. Therefore, in this scenario, giving a recurrent risk of 10-15% appears appropriate. In light of autosomal recessive spinal muscular atrophy and reports of familial FADS due to primary anterior horn cell loss, counselling a 25% risk seems prudent. In cases due to anoxic-ischemic damage, offering a low recurrent risk of 1% appears justified. PMID- 11204283 TI - The pyramidal tract in congenital hemiparesis: relationship between morphology and function in periventricular lesions. AB - Three-dimensional MRI data sets were obtained from 12 young adult patients with congenital spastic hemiparesis caused by unilateral periventricular white matter lesions. The impact of these lesions on corticospinal projections to the upper and lower extremities was assessed on reconstructed semi-coronal planes following anatomical landmarks of somatotopic organization in the precentral gyrus and in the internal capsule: a more anterior plane running through the hand-knob of the precentral gyrus and the anterior portion of the posterior limb of the internal capsule representing projections to the upper extremity, and a more posterior plane running through the top of the precentral gyrus and the middle portion of the posterior limb of the internal capsule representing projections to the lower extremity. In addition, the total lesion extent was determined volumetrically, and Wallerian degeneration was assessed qualitatively in the internal capsule and quantitatively by measuring brainstem asymmetry. We found a strong correlation between motor dysfunction of the upper and lower limb and the lateral extent of the periventricular lesion measured on the respective semi-coronal planes. The total lesion volume and the degree of Wallerian degeneration correlated less strongly, both reaching statistical significance only with motor impairment of the hand. PMID- 11204285 TI - Peculiar respiratory response observed during sleep-onset REM sleep of an infant with Ondine's curse. AB - We treated an infant with congenital central hypoventilation syndrome ("Ondine's curse"). She was cyanotic and given ventilatory support at the first hour after birth. An investigation of sleep state and respiration performed at the age of 3 months led to this diagnosis. Hypoventilation persisted in all sleep stages, with the most severely reduced tidal volumes occurring during delta-wave sleep (stages 3 and 4). In addition, severe secondary reduction in tidal volumes occurred in sleep-onset REM sleep. This phenomenon was absent in non sleep-onset REM sleep. At 4 months of age, her respiratory treatment was successfully converted to positive-pressure ventilation via a nasal mask, thus avoiding tracheotomy. This transition to noninvasive ventilatory support dramatically improved her quality of life during wakefulness. This report may be a clue to discuss the function of sleep-onset REM sleep seen in the early stage of life and suggests that nasal mask ventilation is a viable option in selected cases with congenital central hypoventilation syndrome (CCHS). PMID- 11204284 TI - Brain migration disorder and T-cell activation deficiency associated with abnormal signaling through TCR/CD3 complex and hyperactivity of Fyn tyrosine kinase. AB - In this study we report on a patient affected by a brain migration disorder and a T-cell activation deficiency presumably inherited as an autosomal recessive trait. The immunological evaluation revealed that the mitogen stimulation failed to induce a proper up-regulation of membrane expression of T-cell activation markers, and cell proliferation. This functional impairment was associated with abnormalities of the signal transduction process that follows T-cell receptor stimulation. A constitutive hyperphosphorylation of the Fyn tyrosine kinase was documented. This is the first report on a T-cell signaling abnormality associated with a developmental brain disorder. Whether the alteration of Fyn, which plays a role in both neurological and immunological systems, is responsible for either disorder remains to be elucidated. PMID- 11204286 TI - Intermittent falls and fecal incontinence as a manifestation of epileptic negative myoclonus in idiopathic partial epilepsy of childhood. AB - We report two children, suffering from idiopathic partial epilepsy, who started to present, in the same period of time, with epileptic negative myoclonus (ENM) in one lower limb and fecal incontinence (FI). Polygraphic recordings showed that ENM was associated with paroxysmal activities distributed over the vertex region. Both ENM and FI disappeared when ethosuximide treatment was started. We hypothesize that, in our patients, ENM in one lower limb and FI depended on a transitory impairment, caused by epileptic activity that altered the functionality of nearby cortical areas, located in fronto-mesial regions, involved in the control of the muscular tone of the lower limbs and of the pelvic floor muscles. PMID- 11204287 TI - Single convulsive seizure as isolated neurological complication of mycoplasma pneumoniae infection. PMID- 11204288 TI - Antihypertensive pharmacogenetics: getting the right drug into the right patient. AB - Pharmacogenetic investigation seeks to identify genetic factors that contribute to interpatient and interdrug variation in responses to antihypertensive drug therapy. Classical studies have characterized single gene polymorphisms of drug metabolizing enzymes that are responsible for large interindividual differences in pharmacokinetic responses to several antihypertensive drugs. Progress is being made using candidate gene and genome scanning approaches to identify and characterize many additional genes influencing pharmacodynamic mechanisms that contribute to interindividual differences in responses to antihypertensive drug therapy. Knowledge of polymorphic variation in these genes will help to predict individual patients' blood pressure responses to antihypertensive drug therapy and may also provide new insights into molecular mechanisms responsible for elevation of blood pressure. PMID- 11204289 TI - Serum aldosterone changes during hyperinsulinemia are correlated to body mass index and insulin sensitivity in patients with essential hypertension. AB - OBJECTIVE: To measure the effects of hyperinsulinemia on serum electrolyte status and associated hormones, and on serum free fatty acid (FFA) concentrations, in patients with essential hypertension. DESIGN AND METHODS: The serum electrolyte status (Na, K, Ca, ionized Ca, Mg, P, pH) and associated hormones [plasma renin activity (PRA), serum parathyroid hormone (PTH) and aldosterone concentrations], and FFA were measured during an euglycemic hyperinsulinemic clamp test in 49 patients with untreated essential hypertension. RESULTS: Serum potassium, phosphate, PTH, and FFA concentrations decreased during hyperinsulinemia, while serum ionized calcium concentration, pH, and PRA increased significantly (P < 0.05). The changes in serum potassium and magnesium were both inversely related to the insulin-mediated glucose uptake (r= -0.62, P< 0.0001; r= -0.31, P< 0.05, respectively). Both body mass index (BMI) and insulin-mediated glucose disposal were significantly correlated to the changes in serum aldosterone concentration during hyperinsulinemia (r = 0.41, P < 0.01; r = -0.40, P < 0.01, respectively). The change in serum aldosterone during the clamp test was not significantly related to the change in PRA, but tended to correlate to the change in potassium concentration (r= 0.25, P= 0.10). A less pronounced reduction in FFA during induced hyperinsulinemia was associated with low insulin sensitivity (r= -0.35, P< 0.05). CONCLUSION: Hypertensive patients with normal BMI and a more pronounced glucose uptake showed a larger serum potassium decline and lowered aldosterone concentrations during induced euglycemic hyperinsulinemia. Insulin-resistant patients showed a less pronounced reduction in FFA during hyperinsulinemia. The observations in the present study may indicate that alterations in aldosterone and FFA metabolism might be linked to the insulin resistance metabolic syndrome. PMID- 11204291 TI - Prognostic implications of the compensatory nature of left ventricular mass in arterial hypertension. AB - OBJECTIVE: To test whether inappropriate echocardiographic left ventricular (LV) mass (i.e. higher than predicted by individual body size, sex and cardiac load [delta%LVM]) is associated with an increased rate of cardiovascular events, and whether values of LV mass lower than appropriate confer protection. DESIGN: Prospective, longitudinal. SETTING: Institutional, hospital outpatient clinic. PATIENTS: A total of 294 hypertensive patients, 84 with inappropriate and 21 with low LV mass (lower than appropriate). MAIN OUTCOME MEASURES: Cardiovascular fatal and non-fatal events. RESULTS: Baseline delta%LVM was higher in patients with follow-up total (n = 50) or fatal (n = 14) events than in event-free survivors (all P < 0.0001) and predicted events independently of age and systolic pressure (all P < 0.0001). Although the performance was not better than with use of more traditional definition of LV hypertrophy, delta%LVM remained a predictor even in the subgroup of 126 patients (32 total events, 13 deaths) with clear-cut LV hypertrophy (P < 0.009). Patients with low LV mass exhibited supranormal LV chamber and midwall function, slightly higher heart rate and higher cardiac index (all P< 0.01). These patients had the same rate of events as those with appropriate LV mass. CONCLUSIONS: In hypertensive patients, increase in LV mass beyond values required to compensate cardiac workload at a given body size and sex predicts cardiovascular risk independently of age and blood pressure, in the whole population as well as in the subset of patients with LV hypertrophy. Hypertensive patients with levels of LV mass lower than needed to compensate cardiac workload exhibit hyperdynamic circulatory status and the same risk pattern as patients with higher values of LV mass, possibly due to activation of the sympathetic system. PMID- 11204290 TI - Quinapril treatment enhances vascular sensitivity to insulin. AB - OBJECTIVE: Insulin-mediated vasodilation has been shown to be impaired with hypertension and aggravated by dietary sodium restriction. Whether vascular insulin resistance in this setting could be improved by antihypertensive therapy was unknown. Therefore, we determined the effect of therapy with an angiotensin converting enzyme inhibitor, on vascular sensitivity to insulin in hypertensive subjects fed a sodium-restricted diet. DESIGN AND METHODS: The effects of 3 months of therapy with quinapril on vascular sensitivity to insulin was assessed in 11 hypertensive subjects using a randomized, placebo-controlled, double-blind design. Vascular sensitivity to insulin was assessed by determination of the insulin ED50 from dorsal hand vein linear variable differential transformer in phenylephrine-preconstricted vessels. Subjects were maintained on a 75 mmol/day sodium diet for 3 days prior to each study. RESULTS: Quinapril therapy significantly improved vascular sensitivity to insulin, as assessed by a decrease in the ED50 for insulin (ED50 insulin: placebo = 501 +/- 189 [muU/ min; quinapril = 276 +/- 100 muU/min P < 0.05). Isoproterenol-mediated relaxation was also enhanced by quinapril treatment (maximal isoproterenol-mediated relaxation: Placebo = 92 +/- 15% of baseline distension; Quinapril = 151 +/- 31% P < 0.05). CONCLUSIONS: The current study suggests the hypothesis that the ACE-inhibitor quinapril has beneficial effects on vascular function in general, and on insulin mediated vascular responses, in particular. PMID- 11204292 TI - Relation of left ventricular geometry and function to systemic hemodynamics in hypertension: the LIFE Study. Losartan Intervention For Endpoint Reduction in Hypertension Study. AB - OBJECTIVES: To clarify the relations of systemic hemodynamics to left ventricular (LV) geometric patterns in patients with moderate hypertension and target organ damage. BACKGROUND: LV geometry stratifies risk in hypertension, but relations of LV geometry to systemic hemodynamic patterns in moderately severe hypertension have not been fully elucidated. DESIGN: Cross-sectional case-control study. SETTING: Baseline findings in the echocardiographic substudy of the Losartan Intervention For Endpoint Reduction in Hypertension Study (LIFE) and in a normotensive reference group. PATIENTS/PARTICIPANTS: Nine hundred and sixty-four patients with Stage I-II hypertension and LV hypertrophy by Cornell voltage duration criteria ((SV3 + RaVL [+ 6 mm in women]) x QRS > 2440 mm x ms) or modified Sokolow- Lyon voltage criteria (SV1 + RV5/RV6 > 38 mm), and 366 apparently normal adults. INTERVENTIONS: None. METHODS: Two-dimensional and Doppler echocardiograms were used to classify hypertensive patients into groups with normal geometry, concentric remodelling and concentric and eccentric hypertrophy, and to measure stroke volume (SV), cardiac output, peripheral resistance and pulse pressure/SV as a measure of arterial stiffness. Comparisons were adjusted for covariates by general linear model with the Sidak post-hoc test RESULTS: Mean SV was higher in patients with eccentric hypertrophy (83 ml/beat) and lower with concentric remodeling (68 ml/beat) than in normal adults (73 ml/ beat). Cardiac output was highest in patients with eccentric LV hypertrophy and lower with concentric remodeling than eccentric hypertrophy; mean pressure and peripheral resistance were equally high in all hypertensive subgroups, whereas pulse pressure/SV was most elevated (by a mean of 47% versus reference subjects) with concentric remodeling and least so (mean + 15%) with eccentric hypertrophy. In multivariate analysis (Multiple R + 0.68), LV mass was independently related to higher systolic pressure, older age, SV, male gender and body mass index (all P< 0.001). Relative wall thickness was independently related (Multiple R + 0.50) to older age, higher systolic pressure, lower SV (all P< 0.001) and higher body mass index (P + 0.007). SV and cardiac output were lower in patients with low stress-corrected midwall shortening. CONCLUSION: In patients with moderate hypertension and ECG LV hypertrophy, the levels of SV and pulse pressure/ SV, are associated with, and may be stimuli to different LV geometric phenotypes. PMID- 11204293 TI - Factors affecting the difference between screening and home blood pressure measurements: the Ohasama Study. AB - OBJECTIVE: To establish the factors affecting the difference between screening and home blood pressure measurements. DESIGN: A cross-sectional study. SETTING: General population in a rural Japanese community, Ohasama, Japan. PARTICIPANTS: There were 1,789 community-based subjects aged > or =40 years, for whom blood pressure was measured at screening site (screening blood pressure) and at home (home blood pressure). RESULTS: Multiple stepwise regression analysis of all subjects demonstrated that screening pulse pressure was positively associated with the difference between screening and home blood pressure measurements for systolic blood pressure. Age, the use of antihypertensive medication, and smoking status were negatively associated with the difference between measurements of both systolic and diastolic blood pressure. CONCLUSION: We have demonstrated that age, smoking, antihypertensive medication, and screening pulse pressure are independent predictors of the magnitude of the difference between screening and home blood pressure measurements, suggesting that the necessity to consider these factors, for the detection of the subjects who may be inappropriately treated or misjudged following screening blood pressure measurements. PMID- 11204294 TI - Indexation of left ventricular mass in adults with a novel approximation for fat free mass. AB - BACKGROUND: Indexation to fat-free mass (FFM) seems to be the best option for adjusting left ventricular (LV) mass. However, measurements of FFM are frequently not available. OBJECTIVES: To define the relation of FFM with commonly available anthropometric measures in order to derive an approximation formula of FFM that can be used for valid indexation of LV mass. SUBJECTS AND METHODS: A total of 1,371 subjects from a community survey were examined by echocardiography to measure LV mass and by bioelectrical impedance analyses (BIA) for the determination of FFM. An approximation of FFM was generated in a healthy subgroup of 213 men and 291 women by non-linear regression techniques. RESULTS: Compared with body height, height2.0, height2.7, (the superscripts following weight and height are raised powers used as a more appropriate method for indexing LV mass) or body surface area, FFM measured by BIA in the healthy subgroups was best predicted by gender-specific equations of the form: FFM = 5.1 x height1.14 x weight0.41 for men and FFM = 5.34 x height1.47 x weight0.33 for women. In the healthy reference group, indexation of LV mass for BIA-determined FFM and approximated FFM (FFMa), respectively, equally eliminated gender differences in LV mass and markedly reduced the influence of body mass index without affecting the associations between blood pressure and LV mass. Validation of FFMa in two independent population-based samples, aged 52 to 67 years, of the same source population confirmed that LV mass indexed by FFMa produced results that were highly consistent with those obtained with indexation by BIA-determined FFM. CONCLUSIONS: We propose a novel approximation of FFM based on exponentials of body height and weight. It performed well in the indexation of LV mass in middle aged men and women of this study. Evaluation of the equation in other populations should be awaited before its use is recommended in situations where direct determination of FFM is not possible. PMID- 11204295 TI - Influence of gender and family history of hypertension on autonomic control of heart rate, diastolic function and brain natriuretic peptide. AB - OBJECTIVE: To verify in a unitary view whether autonomic control of heart rate and cardiac structure and function are modified early in offspring of hypertensive families. METHODS AND RESULTS: We selected 87 age- and sex-matched young normotensive subjects with (n = 45) and without (n = 42) a family history of hypertension who underwent evaluations of arterial pressure, time-domain parameters of autonomic heart rate control (24-h ECG monitoring), spectral baroreflex sensitivity, left ventricular geometry and function (echo-Doppler) and plasma brain natriuretic peptide levels (BNP). The group with a family history of hypertension significantly differed from their counterparts for systolic pressure (119 +/- 11 versus 114 +/- 9 mmHg, P< 0.05), heart rate (RR interval, 766 +/- 64 versus 810 +/- 93 ms, P< 0.05), heart rate variability [the standard deviation of normal RR intervals (SDNN), 147 +/- 29 versus 171 +/- 33 ms, P < 0.051, diastolic function (isovolumetric relaxation time, 65 +/- 9 versus 60 +/- 8 ms, P< 0.05) and BNP (23 +/- 13 versus 37 +/- 10 pg/ml, P< 0.05). Baroreflex sensitivity values did not differ between the two groups. When gender was considered, all the above-mentioned measures, as well as baroreflex sensitivity, were significantly different between males with and without a family history of hypertension but not between females, except for BNP, which was lower in males and females with a history of hypertension (males, 24 +/- 11 versus 38 +/- 8 pg/ml, P< 0.01; females 21 +/- 14 versus 36 +/- 13 pg/ml, P < 0.05). CONCLUSIONS: Male, but not female, hypertensive offspring have modified diastolic function and autonomic control of heart rate; BNP is the only parameter able to characterize hypertensive offspring independently from the influence of gender. This provides the hypothesis that the impaired production of this hormone could play a primary role in the pre hypertensive state. PMID- 11204296 TI - Which is more important for the efficiency of hypertension treatment: hypertension stage, type of drug or therapeutic compliance? AB - OBJECTIVES: Hypertensive patients are a heterogeneous population that can be distributed in groups showing different cardiovascular risk and benefit from treatment. This study examines the cost-effectiveness of arterial hypertension treatment by age, sex, arterial hypertension stage, type of drug used and level of treatment compliance. DESIGN: Markov models combining absolute risks for stroke, coronary heart disease and all causes of death with relative risks from clinical trials and observational studies. Data on health costs were collected from hospitals and primary care settings in the Basque Country (Spain). RESULTS: Cost-effectiveness ratios vary from 34,516 euros/quality adjusted life year (QALY) gained in 30-year-old women to 3,307 euros/QALY in 80-year-old men. A treatment compliance of 50% increases these values to 45,270 and 4,905 euros/QALY, respectively. Treatment of arterial hypertension stage II shows lower ratios (19,798 euros/QALY in 30-year-old women and 1,918 euros/QALY in 80-year old persons). Cost-effectiveness ratios for arterial hypertension stage I vary from 645 euros/QALY in 80-year-old men for diuretics to 47,325 euros/QALY in 30 year-old women for inhibitors of the angiotensin converting enzyme. CONCLUSIONS: There are large variations in the cost-effectiveness of arterial hypertension treatment depending on age, sex, arterial hypertension stage, drug used and compliance. Improvement of treatment compliance yields the greatest gain both in effectiveness and efficiency. PMID- 11204297 TI - The baroreflex bandwagon: time to get off? PMID- 11204298 TI - Effect of oral magnesium supplementation on blood pressure, platelet aggregation and calcium handling in deoxycorticosterone acetate-induced hypertension in rats. PMID- 11204299 TI - Growth in utero and blood pressure levels in the next generation. PMID- 11204300 TI - Cardiovascular responsivity to stress in adolescents with and without persistently elevated blood pressure. AB - OBJECTIVES: The goal of this study was to compare the cardiovascular responses to behavioural stressors of three groups of adolescents who differed in blood pressure status across assessments. DESIGN: Casual blood pressure of adolescents who were identified as having elevated blood pressure during a school screen was re-evaluated in the laboratory. The adolescents were classified into two groups: (i) those with consistently elevated blood pressure across school and laboratory assessments and (i) those with labile blood pressure whose blood pressure in the laboratory was below 130/80 mmHg. A comparison group of adolescents with consistently normal blood pressure was also included. METHODS: Cardiovascular parameters were assessed during rest and during two behavioural stressors, the evaluated speaking task and the mirror tracing task. RESULTS: Adolescents with elevated blood pressure were more vascularly responsive across stressors than adolescents with labile blood pressure, who, in turn, were more reactive than adolescents with normal blood pressure. CONCLUSIONS: These results suggest that vascular reactivity to behavioural stressors may be useful in predicting risk of hypertension because of its sensitivity in distinguishing adolescents with consistently elevated blood pressure from those with labile blood pressure and those with normal blood pressure. PMID- 11204301 TI - Maternal nutrition during gestation and blood pressure in later life. AB - OBJECTIVE: To assess the link between maternal diet during pregnancy and blood pressure of the offspring. DESIGN: Follow-up study. SETTING: A university hospital in Amsterdam, The Netherlands. PARTICIPANTS: People born at term as singletons between November 1943 and February 1947. MAIN OUTCOME MEASURE: Blood pressure at adult age. RESULTS: Adult blood pressure was not associated with protein, carbohydrate or fat intake during any period of gestation. We found, however, after adjustment for sex that the systolic blood pressure decreased by 0.6 mmHg (0.1-1.1) for every 1% increase in protein/carbohydrate ratio in the third trimester. This association was present both in people who had been exposed to the famine during gestation as well as in those who had not been exposed. The association between protein/carbohydrate ratio in the third trimester and adult blood pressure was furthermore independent of maternal weight gain and final weight, and birth weight [increase for every 1% increase in protein/carbohydrate ratio 0.6 mmHg (0.0-1.2)]. Adjustment for adult characteristics such as body mass index, smoking and socio-economic status did not affect the observed association appreciably [adjusted increase 0.5 mmHg (0.0-1.0)]. CONCLUSION: Adult blood pressure seems to be affected by small variations in the balance of macro nutrients in the maternal diet during gestation rather than by relatively large variations in the absolute amounts. PMID- 11204302 TI - Blood pressure and mortality during an up to 32-year follow-up. AB - BACKGROUND: Elevated blood pressure is an established risk factor of cardiovascular diseases, but there is a constant debate whether the association is continuous or with a threshold. METHODS: During the 1960s (1964 onwards), 3,267 initially healthy male business executives (born 1919-1934) participated in voluntary health check-ups with measurements of cardiovascular disease risk factors. At baseline none of the men were on antihypertensive medication. Mortality follow-up was performed using national registers up to 31 December, 1995. Follow-up total and cardiovascular mortality was related to systolic (by 10 mmHg) and diastolic (by 5 mmHg, Korotkoff's 4th phase) blood pressure at baseline. Analyses were adjusted for age, body mass index, smoking and serum cholesterol. RESULTS: During an up to 32-year follow-up, there were 701 deaths, 234 (33.4%) of them due to coronary heart disease, 49 (7.0%) to stroke, 42 (6.0%) to other cardiovascular diseases and 204 (29.1%) to cancer. Total mortality curves of the whole cohort (all age groups) were flat until 131-140 mmHg (systolic) and 81-85 (diastolic) and increased thereafter. Among men who smoked and had baseline serum cholesterol > 6.5 mmol/l (n = 986), the risk of death increased progressively with systolic blood pressure, whereas among non-smoking normocholesterolaemic men (n = 504) the association was J-shaped, i.e. higher mortality at < or = 110 mmHg than between 111-150 mmHg and a more consistent rise from 151-160 mmHg. The curves were essentially similar for cardiovascular mortality. The results were supported by analyses where major cardiovascular risk factors were controlled. CONCLUSION: During a truly long-term follow-up, the relationship between systolic blood pressure and mortality was initially flat up to 131-140 mmHg although a linear relationship is suggested in men with other cardiovascular risk factors. PMID- 11204303 TI - Hypertension in four African-origin populations: current 'Rule of Halves', quality of blood pressure control and attributable risk of cardiovascular disease. AB - OBJECTIVE: To assess the public health burden from high blood pressure and the current status of its detection and management in four African-origin populations at emerging or high cardiovascular risk. DESIGN: Cross-site comparison using standardized measurement and techniques. SETTING: Rural and urban Cameroon; Jamaica; Manchester, Britain. SUBJECTS: Representative population samples in each setting. African-Caribbeans (80% of Jamaican origin) and a local European sample in Manchester. MAIN OUTCOME MEASURES: Cross-site age-adjusted prevalence; population attributable risk. RESULTS: Among 1,587 men and 2,087 women, age adjusted rates of blood pressure > or =160 or 95 mmHg or its treatment rose from 5% in rural to 17% in urban Cameroon, despite young mean ages, to 21% in Jamaica and 29% in Caribbeans in Britain. Treatment rates reached 34% in urban Cameroon, and 69% in Jamaican- and British-Caribbean-origin women. Sub-optimal blood pressure control (> 140 and 90 mmHg) on treatment reached 88% in European women. Population attributable risks (or fractions) indicated that up to 22% of premature all-cause, and 45% of stroke mortality could be reduced by appropriate detection and treatment. Additional benefit on just strokes occurring on treatment could be up to 47% (e.g. in both urban Cameroon men and European women) from tighter blood pressure control on therapy. Cheap, effective therapy is available. CONCLUSION: With mortality risk now higher from non-communicable than communicable diseases in sub-Saharan Africa and elsewhere, systematic measurement, detection and genuine control of hypertension once treated can go hand-in-hand with other adult health programmes in primary care. Cost implications are not great. The data from this collaborative study suggest that such efforts should be well rewarded. PMID- 11204304 TI - Angiotensin converting enzyme genetic polymorphism is not associated with hypertension in a cross-sectional sample of a Japanese population: the Shibata Study. AB - BACKGROUND: The studies on the association of deletion/ insertion (D/I) polymorphism of angiotensin converting enzyme (ACE) gene with blood pressure and hypertension reported contradictory results. Because there was no population based study in Japan, we examine the hypothesized association in a cross sectional sample of a Japanese cohort. METHODS AND RESULTS: The blood pressure of 464 men and 876 women aged 40-80 years was measured, and their DNA was analyzed for ACE D/I genotypes. The prevalence of the D allele was 38.7 and 39.2% in men and women, respectively (overall 39%). There was a tendency for higher covariate (age, body mass index, albuminuria, hematocrit, alcohol consumption, smoking, diabetes mellitus, ischemic heart disease and antihypertensive medication) adjusted mean levels of diastolic blood pressure for the DD genotype in men but not in women. However, this tendency disappeared after dichotomization of blood pressure into diagnostic categories (normotension and hypertension). Results did not differ when the subjects were divided into two age groups (< or = 59 and > or = 60 years). Covariate-adjusted odds ratios for hypertension for presence of the D allele were close to the null value of one. ACE genetic variation accounted for only 0.1 and 0.7% of the inter-individual variation in systolic and diastolic blood pressure in men. These estimates were 0.2 and 0.1%, respectively, in women. CONCLUSION: Although there is a tendency of higher diastolic blood pressure in men with DD genotypes, there is no convincing evidence that ACE genotypes are associated with hypertension in this Japanese population. PMID- 11204305 TI - Linkage of hypertension to chromosome 2q14-q23 in Chinese families. AB - OBJECTIVES: To identify chromosome regions containing hypertension susceptibility genes in Chinese. SUBJECTS AND METHODS: A three-stage study was carried out in Chinese siblings ascertained through outpatient clinics. In the first stage, 283 affected sib-pairs from 79 nuclear families were subjected to a genome-wide scan with 240 microsatellite marker loci. The second stage focused on chromosome 2 with additional markers resulting in an average distance of 5 cM and used an independent sample of 637 affected sib-pairs from 161 families. In the third stage, a fine-scale mapping study on the suggestive region was performed in an independent set of 777 affected sib-pairs from 106 families. Fourteen markers were used with an average distance less than 2 cM. Non-parametric linkage analyses (NPL), parametric linkage analyses and transmission-disequilibrium tests were used to assess evidence for linkage and association. RESULTS: Three markers (D2S168 at 27.06 cM, D2S151 at 152.04 cM and D2S142 at 161.26 cM) on chromosome 2 with suggestive linkage to hypertension susceptibility genes were identified in the genome-wide scan. In stage II, the suggestive region around D2S151 and D2S142 was replicated, while the linkage around D2S168 was not. In the stage III fine scale mapping study, multipoint linkage analyses showed LOD scores greater than 2.0 throughout a region between 157.16 cM and 162.46 cM (all P < 0.001) with a maximum peak of 2.24 (P= 0.00067) at 160.52 cM. We also observed a NPL Z-score peak of 3.27 at 157.55 cM (P= 0.00086). CONCLUSIONS: The results of a suggestive region on chromosome 2q14-q23 (D2S112-D2S2370) were consistent between each of the three studies. Interestingly, this region overlaps a syntenic region that contains blood pressure quantitative trait loci identified in rat models of hypertension. These data suggest that the region near D2S142 and D2S151 deserves to be further screened for hypertension susceptibility genes. PMID- 11204306 TI - Impaired ceramide signalling in spontaneously hypertensive rat vascular smooth muscle: a possible mechanism for augmented cell proliferation. AB - OBJECTIVES: In hypertension, the vascular wall undergoes morphological changes that alter mechanical responses to vasoactive substances. Ceramide is a recently identified second messenger synthesized in response to cytokines such as tumour necrosis factor alpha (TNF-alpha). It has been previously demonstrated that vascular smooth muscle cells (VSMC) from genetically hypertensive rats proliferate at a higher rate than those of normotensive origin. We tested the hypothesis that the ceramide pathway is impaired in VSMC from spontaneously hypertensive rats (SHR). DESIGN: VSMC were isolated from aortae of SHR and from Wistar-Kyoto (WKY) rats. Ceramide levels were measured under baseline and agonist stimulated conditions and cell proliferation was monitored. METHODS: Cell proliferation was determined by cell counting. Ceramide levels were determined via radioactive labelling, high-performance thin-layer chromatography and phosphorimaging. Relative mRNA levels of neutral sphingomyelinase were determined using semi-quantitative polymerase chain reaction (PCR). RESULTS: Basal ceramide levels in untreated cells were lower in cells from SHR compared to WKY rats. During chronic treatment with TNF-alpha, ceramide levels increased in WKY rat cells but remained unchanged in cells from SHR. TNF-alpha treatment had an inhibitory effect on WKY rat VSMC proliferation, but stimulated proliferation in cells from SHR. Short-term incubation with TNF-alpha resulted in a greater increase in ceramide in cells from WKY rats than those from SHR. Semiquantitative PCR analysis indicated that neutral sphingomyelinase mRNA may be reduced in SHR VSMC. CONCLUSIONS: We conclude that ceramide synthesis is impaired in vascular smooth muscle from SHR and may contribute to increased VSMC proliferation in hypertension. PMID- 11204307 TI - Effects of physical training of the dominant arm on ipsilateral radial artery distensibility and structure. AB - BACKGROUND: Exercise training induces cardiovascular changes that are both generalized and restricted to the microcirculation of the tissues more actively involved in the exercise itself. Whether the local effect of exercise extends to larger arteries is unknown, however. METHODS: In the right and left upper limb of 17 right-handed subjects performing an asymmetric training of the upper limbs (hammer throwers and baseball players) and 16 age-matched sedentary controls, we continuously measured radial artery diameter, distensibility and wall thickness by an echotracking and a beat-to-beat finger blood pressure device. Arterial distensibility was calculated by the arctangent model of Langewouters and expressed as continuous values from diastolic to systolic blood pressure. Measurements were made: (1) in baseline conditions; (2) after release from prolonged proximal ischaemia; and (3) after an increase in radial artery blood flow caused by a short (4 min) distal ischaemia to determine the endothelial involvement in the training-induced change in arterial distensibility. RESULTS: In athletes the radial artery distensibility was markedly greater in the right than in the left arm, the latter showing values slightly greater than those seen in the two arms of sedentary subjects. In both arms and groups radial artery distensibility increased markedly after prolonged ischaemia, the between arm and group differences being preserved, however. The radial artery response to distal short ischaemia was, on the other hand, similar in the two arms of the athletes, although greater in these subjects than in the sedentary ones. Radial artery wall thickness was greater in the trained than in the untrained arm of athletes, both values being greater than in sedentary subjects. CONCLUSIONS: Asymmetrical training of the upper limbs is accompanied by a greater distensibility of the middle-sized arteries of the more trained side. This is not associated with asymmetrical changes in endothelial structure or function. It is associated with a greater wall thickness in the trained side, suggesting that, at least in part, a training-induced asymmetrical change in wall structure (possibly with a predominance of more distensible tissues such as elastine and smooth muscle) is responsible. PMID- 11204308 TI - Systolic and pulse blood pressures (but not diastolic blood pressure and serum cholesterol) are associated with alterations in carotid intima-media thickness in the moderately hypercholesterolaemic hypertensive patients of the Plaque Hypertension Lipid Lowering Italian Study. PHYLLIS study group. AB - OBJECTIVE: The Plaque Hypertension Lipid Lowering Italian Study (PHYLLIS), is the first study in patients with hypertension (diastolic blood pressure (DBP) 95-115 mmHg; systolic blood pressure (SBP) 150-210 mmHg), moderate hypercholesterolaemia (LDL-cholesterol 4.14-5.17 mmol/l (160-200 mg/dl) and initial carotid artery alterations (maximum intima-media thickness (IMT) Tmax > or = 1.3 mm). The primary objective of PHYLLIS is investigating whether in these patients administration of an angiotensin converting enzyme inhibitor, fosinopril, and a statin, pravastatin, is more effective than administration of a diuretic and a lipid-lowering diet in retarding or regressing alterations in carotid IMT. While the study is in progress, baseline data are here reported to clarify the association of various risk factors with carotid IMT in these medium-high risk hypertensive patients. METHODS: Patients numbering 508 have been randomized to PHYLLIS by 13 peripheral units, in Italy. Age was (mean +/- SD) 58.4 +/- 6.7 years, males were 40.2%, current smokers 16.5%, means +/- SD of serum total, low density lipoprotein (LDL), high-density lipoprotein (HDL) cholesterol and triglycerides concentrations were 6.79 +/- 0.67, 4.69 +/- 0.51, 1.37 +/- 0.38, 1.59 +/- 0.64 mmol/l (262.4 +/- 25.8, 181.3 +/- 19.8, 53.0 +/- 14.6, 141.0 +/- 56.7 mg/ dl). Means +/- SD of clinic sitting SBP/DBP were 159.8 +/- 9.0/98.3 +/- 4.2 mmHg. 483 of the 508 patients also had 24 h ambulatory BP monitoring, edited and read at a centralized unit (mean +/- SD 24 h SBP/DBP averages 136.3 +/- 14.1/84.0 +/- 10.0 mmHg). Quantitative B-mode ultrasound (Biosound 2000 II 5A, Biosound, Indianapolis, Indiana, USA) recordings of carotid arteries were taken by certified sonographers in the peripheral units and tracings were all read at a central unit. CBMmax (mean IMT of eight sites at common carotids and bifurcations) was 1.21 +/- 0.17; Mmax (mean of 12 sites also including internal carotids) 1.16 +/- 0.17, and Tmax (single maximum) 1.85 +/- 0.48 mm. RESULTS: Ambulatory SBP and pulse pressure (PP) (24 h, daytime, night-time averages) and their variability indices (24 h SD) were always significantly correlated with CBMmax and Mmax (P0.01 -0.001), and the correlations remained significant after adjustment for age, gender and smoking. No measurement of DBP was ever associated with any IMT measurement. Likewise, no lipid variable was found associated with any IMT measurement. CONCLUSIONS: Baseline data from PHYLLIS indicate that in this population of hypertensive patients with moderate hypercholesterolaemia, SBP and PP are with age among the most significant factors associated with carotid artery alterations. However, the narrow range of inclusion LDL-cholesterol and DBP values may have obscured an additional role of these variables. PMID- 11204310 TI - Insulin resistance in hypertensives: effect of salt sensitivity, renin status and sodium intake. AB - OBJECTIVE: Homeostasis Model Assessment (HOMA index) is predictive of insulin sensitivity in normal and diabetic patients. This study was designed to see if insulin resistance in hypertensives, measured using the HOMA index, differs, based on salt sensitivity, renin status and sodium intake. METHODS: Fasting insulin and glucose were determined in subsets of 426 essential hypertensives, and normotensives. HOMA was calculated as fasting glucose (mmol) x fasting insulin (muU/ml)/22.5. RESULTS: Four hundred and twenty-six essential hypertensives and normotensives from four HERMES centers form the basis of this report. There was no difference in the HOMA index between hypertensives and normotensives (P= 0.291) or between hypertensives grouped according to blood pressure salt sensitivity (P = 0.153). However, when essential hypertensives were subgrouped by renin status, the low-renin group had significantly lower (P< 0.01) HOMA index than the normal/high-renin group. When normal/high-renin group was divided into modulators and non-modulators, the nonmodulators had significantly higher HOMA index (P< 0.001) than other hypertensive subsets. The effect of sodium intake on the HOMA index was significant only for non-modulators (P< 0.002), with salt restriction increasing insulin resistance. CONCLUSION: Insulin sensitivity differs among subsets of essential hypertension, non-modulators being most insulin resistant and the low-renin subset insulin sensitive. Salt restriction might have an adverse effect on insulin sensitivity in non modulators. The reduction in cardiovascular risk seen in low-renin hypertensives may be related to their increased insulin sensitivity; in contrast, the clustering of cardiovascular risk factors seen in nonmodulators may be due to increased insulin resistance. PMID- 11204311 TI - [A centennial of "The Interpretation of Dreams"]. PMID- 11204309 TI - High salt intake and the brain renin--angiotensin system in Dahl salt-sensitive rats. AB - OBJECTIVES: To assess changes in the activity of the brain renin-angiotensin system during (i) the development of salt-sensitive hypertension; and (ii) the prevention of salt-sensitive hypertension by blocking brain 'ouabain'. METHODS: In protocol I, angiotensin converting enzyme (ACE) mRNA and activity and angiotensin I and II levels were assessed in the hypothalamus and pons of Dahl salt-sensitive (Dahl S) and salt-resistant (Dahl R) rats on regular (120 micromol Na+ per g) or high (1370 micromol Na+ per g) salt diet from 4-6 weeks or 4-9 weeks of age. In protocol II, ACE mRNA and activity were assessed in the hypothalamus and pons in Dahl S on regular or high salt treated with intracerebroventricular (i.c.v.) Fab fragments blocking brain 'ouabain' or gamma globulins, and in Dahl R on high or regular salt ACE mRNA was assessed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay and angiotensin I and II by radioimmunoassay after high-performance liquid chromatography. In protocol III, effects of i.c.v. angiotensin I and i.c.v. bradykinin on renal sympathetic nerve activity (RSNA), heart rate and blood pressure before and after i.c.v. captopril were assessed in Dahl S and R rats on regular or high salt intake from 4-8 weeks of age. RESULTS: High salt diet caused a gradual, but marked increase in blood pressure in Dahl S but not Dahl R rats. Dahl S rats showed small but significant increases in ACE mRNA in the hypothalamus on regular salt diet. In Dahl S rats on high salt diet for 2 or 5 weeks ACE mRNA levels significantly increased in both hypothalamus and pons, compared with Dahl R rats on either diet or Dahl S rats on regular diet. After 5 weeks of high salt diet, ACE mRNA levels in the hypothalamus in Dahl S rats were almost three-fold higher and in the pons two-fold higher than in Dahl R rats on either diet or Dahl S on regular salt diet. High salt diet also increased ACE activity of the hypothalamus and pons in Dahl S but not Dahl R. Consistent with this increased ACE activity, central responses to angiotensin I were clearly enhanced and to bradykinin markedly diminished in Dahl S on high salt intake. Chronic blockade of brain 'ouabain' by i.c.v. Fab fragments prevented the increases in blood pressure, ACE mRNA and activity in the hypothalamus and pons by high salt intake in Dahl S rats. Angiotensin I levels in the hypothalamus and pons were similar in both groups of rats and there were no significant changes caused by high salt diet in Dahl S and R rats. On regular salt intake angiotensin II levels in the hypothalamus of Dahl S rats showed a significant decrease as compared with Dahl R rats on regular salt diet, and were similar in the pons of the two strains. High salt intake did not affect angiotensin II levels in either hypothalamus or pons in Dahl S and R rats. CONCLUSIONS: These results indicate that high salt intake increases blood pressure, ACE expression and activity in the hypothalamus and pons of Dahl S rats without a parallel increase in angiotensin II levels. Effects of high salt intake on ACE mRNA and activity appear to be secondary to activation of brain 'ouabain'. PMID- 11204312 TI - [Atypical neuroleptics: new approaches to drug therapy of schizophrenic disorders]. AB - The introduction of conventional antipsychotics revolutionized the management of psychotic disorders in the 1950s. The use of these agents has been marked by several shortcomings, including their association with severe motor disturbances and their limited efficacy in treating the negative and cognitive symptoms of schizophrenia. Patients noncompliance has largely been the result of subjectively distressing extrapyramidal motor side-effects (EPMS). It was therefore necessary to develop antipsychotic drugs with selective pharmacological profiles, e.g. limbic selectivity. A defining characteristic of atypical neuroleptics is a higher ratio of serotonin receptor blockade to D2 receptor blockade. Their primary advantage is their superior side-effect profile. The implications of EPMS reduction touch several domains of pathology in schizophrenia such as short- and long-term movement disorders, noncompliance, relapse rate, negative symptoms and cognitive dysfunction. Novel antipsychotics may represent the second pharmacological revolution in the treatment of psychotic disorders. There is, however, still a need for a critical evaluation of the risk-benefit-ratio of differing atypical agents. PMID- 11204313 TI - [Unusual cause of leg venous thrombosis in a 20-year-old man]. PMID- 11204314 TI - [Bed rest after lumbar puncture: a nation-wide survey in Austria]. AB - BACKGROUND: Recommendations in medical textbooks concerning bed rest after lumbar puncture to prevent postpunctional headache vary between immediate mobilisation and 24 hours bed rest. AIM OF THE STUDY: The aim of the study was to evaluate the current practice in neurological departments. METHODS: We contacted all neurological departments in Austria by fax and asked about standards concerning bed rest after lumbar puncture and about the number of punctures per month. RESULTS: 28 out of 32 departments replied (88%). Fifty percent (n = 14) of the departments recommend 24 hours bed rest after lumbar puncture, recommendations of the other departments vary between immediate mobilisation (one department) and 16 hours bed rest. CONCLUSION: Current practice concerning bed rest after lumbar puncture varies widely in Austria and most patients are confined to bed for several hours. Even though there is evidence that bed rest does not prevent post lumbar puncture headache, there is so far no systematic review published in the medical literature. PMID- 11204315 TI - The value of serum CA 125 for the management of tubo-ovarian abscesses. AB - OBJECTIVE: The aim of this study was to compare the value of CA 125, ESR and CRP in predicting the outcome of tubo-ovarian abscess (TOA) treatment and to investigate whether TOA treatment could be improved by following the dynamics of CA 125 serum levels. STUDY DESIGN: This prospective study included 36 patients with unilateral TOA, confirmed on the basis of history and physical examination, laboratory findings, and ultrasound (US) investigation. Venous blood samples for estimation of serum CA 125, CRP, and ESR were taken on hospital admission and then every 5 days. On day 20, the success of treatment was evaluated by clinical and sonographical re-assessment, and the patients were divided into two groups: those with complete regression of the TOA and those with residual inflammatory disease. Statistical analysis was performed by nonparametric Mann-Whitney U-test with multiple regression. RESULTS: On admission, CA 125 levels were increased (> 16.7 U/ml) in 32 patients (88.9%). The CA 125 level amounted to 55.7 U/ml on the average. A significant difference in CA 125 values between the above mentioned two groups was observed from day 10 of treatment onwards (p = 0.00015). On comparison of ESR, CRP, and CA 125, the latter had the highest predictive value for disease outcome after day 10 (p < 0.0011), while at the time of diagnosis, ESR proved more reliable in predicting the outcome. CONCLUSIONS: The dynamics of serum CA 125 allow an objective evaluation of the course and outcome of TOA, in combination with clinical parametres and US investigation. PMID- 11204316 TI - [Multiple organ failure following inhalation of butane gas: a case report]. AB - Most cases of acute poisoning by butane and other volatile compounds occur in young people as a consequence of substance abuse by inhalation. Clinical symptoms are caused by asphyxia and mainly affect the cardiovascular, respiratory and central nervous system. There are also reported deaths from intoxication of butane inhalation, mostly by cardiac arrhythmia. We report the case of a healthy 14 year-old boy who inhaled butane gas from an aerosol can for refilling cigarette lighters. Despite successful resuscitation and defibrillation, he died two days later from multiple organ failure involving the central nervous system, cardiovascular system, pulmonary system and the liver. Although such incidents are rare in middle European countries, emergency and intensive care medicine staff should be instructed on the consequences and management of butane gas poisoning. PMID- 11204318 TI - Can it be worse? On the sub-Saharan HIV/AIDS epidemic at the beginning of the new millennium. AB - According to the data in the relevant literature, it seems that at the millennium the worldwide HIV/AIDS epidemic shows no decline. In the most heavily affected area of tropical (sub-Saharan) Africa the situation is getting worse. There is a number of factors which are responsible for this situation. Considering the lack of necessary funds, it is evident that the most important task is a vigorous health education. PMID- 11204317 TI - [Hemorrhagic diathesis as initial symptom of stomach carcinoma]. AB - BACKGROUND: Microangiopathic hemolytic anemia (MAHA) and disseminated intravasal coagulation (DIC) as initial paraneoplastic symptoms of a solid tumor present a rare clinical situation. CASE REPORT: In 1998 a female patient was admitted due to multiple thrombosis, thrombocytopenia and fever. The initial diagnostic procedures revealed peri-aortic lymphomas and a tumor bulk (7 x 8 cm) in the upper abdomen. Gastroscopy revealed a 2 cm ulcer at the back side of the gastric corpus. Histologically, a signet-ring cell carcinoma was diagnosed. Final diagnosis stated a multilocular metastasising gastric cancer with infiltration of bone, peritoneum and dura and signet-cell infiltration of the bone marrow. Hematologic investigation in view of multiple paraneoplastic thrombosis revealed a microangiopathic hemolytic anemia associated with disseminated intravasal coagulation. Parallel to initial symptomatic therapy of coagulopathy, systemic cytostatic therapy with CDDP and VP-16 was initiated. In addition, radiotherapy of the brain was performed. After histologic confirmation of the diagnosis, weekly therapy with 5-FU (2600 mg/m2) and folinic acid (500 mg/m2) according to the Ardalan protocol was performed. After first signs of moderate response, oxaliplatin (60 mg/m2, day 1) was added. Although the chemotherapy dose had to be reduced due to prolonged neutropenia, the disturbances of hemostasis resolved completely resulting in reduced substitution rates with fresh frozen plasma (FFP) and platelets. Unfortunately, the patient died at home due to pulmonary embolism. CONCLUSION: Tumor-associated hemostaseologic alteration requires immediate substitution of FFP and platelets. However, it should be followed by specific therapy of malignancy, since tumor-induced metabolites (e.g. mucin) maintain the alteration of hemostasis. Chemotherapy may therefore be the best strategy to prevent complications such as MAHA and DIC. PMID- 11204319 TI - [The role of pharmacotherapy for treatment of obesity in adults]. AB - Obesity is one of the pathologies with ever-increasing prevalence in modern societies. Its occurrence is strongly associated with increased risk of developing diabetes mellitus, atherosclerosis, hypertension, stroke, heart and respiratory failure, breast, prostate and gut cancer, gall stones, arthropathy. Obesity is common in Polish population. Obesity treatment is difficult and frustrating. It consists of several parts like diet, increased physical activity, lifestyle changes, drug therapy and surgery. However, obesity treatment is very often a failure, mostly because of discouraging long-term results and the necessity of intensive patient's involvement in the therapy. For many patients and doctors weight-decreasing agents look promising. The groups of anti-obesity drugs are presented in the article, with special reference to serotoninergic agents and intestinal lipase inhibitors. The prospects for new anti-obesity agents are discussed. Nevertheless, despite intensive research on obesity, we are still waiting for the development of an effective and safe drugs helping lose weight. PMID- 11204320 TI - [Predominance of multidrug resistant strains with reduced susceptibility to fusidic acid among methicillin-resistant Staphylococcus aureus strains (MRSA) isolated in the Gdansk region]. AB - The aim of the present study was to follow the changes in the drug resistance among the methicillin-resistant Staphylococcus aureus strains (MRSA) isolated from clinical samples in various hospitals during 8 years, with particular consideration of Gdansk area. The study was carried out on 225 strains of MRSA from which 95 were isolated in the years 1990-1995 and 130 in the years 1997 1998. The drug susceptibility was determined by the disc-diffusion method. The sensitivity to fusidic acid was determined by both disc-diffusion method and minimal inhibitory concentration (MIC) using agar dilutions. The results obtained show that in 1997-1998 in the hospitals of Gdansk area have been appeared MRSA strains which have not occurred before. These strains were intermediately sensitive or resistant to fusidic acid and simultaneously resistant to doxycycline, gentamicin, erythromycin, clindamycin, ciprofloxacin and rifampin. They represented 66.2% of all MRSA strains isolated in 1997-1998 and were present in majority of the hospitals monitored. Only in this group of staphylococci the strains additionally resistant to mupirocin (6.2%) occurred. Among the MRSA strains with reduced susceptibility to fusidic acid 64.4% were intermediately sensitive (MIC 8-16 mg/L) and 15.4% were resistant to this drug (MIC > 16). In 1997-1998 the percentages of MRSA strains resistant to rifampin, clindamycin and ciprofloxacin increased significantly from 12.6% to 90.8%, from 42.1% to 92.3% and from 18.9% to 92.3% respectively. The percentage of the chloramphenicol resistant strains decreased from 14.7% to 0.8%. Like in 1990-1995, the MRSA strains resistant to vancomycin and teicoplanin were not found out in the same period of time. PMID- 11204321 TI - [Risk factors for inner ear diseases]. AB - The aim of this study was to evaluate the occurrence of obesity and arterial hypertension in patients suffering from vertigo, and/or tinnitus and/or hearing loss of unknown origin. 48 patients (25 women and 23 men) were included into this study. All patients had a negative previous medical history of any metabolic, cardiovascular or neurological disorders. Our results were compared to the control group of 31 healthy persons (16 women and 15 men). All subjects had a complete neurootologic examination, appropriate audiometric and vestibular studies. In most cases inner ear pathology was recognised. BMI, systolic and diastolic blood pressure were measured in all cases. Patients were overweight significantly more often comparing to the control group. Systolic and diastolic hypertension was found significantly more often in men from the patients than control group. PMID- 11204322 TI - [Procalcitonin in diagnosis of purulent and aseptic meningitis in children]. AB - Procalcitonin (PCT) is a new indicator of the systemic response to severe infections. To evaluate clinical usefulness of serum procalcitonin measurements in the differential diagnosis of purulent versus aseptic meningitis in children was the aim of the study. Fifteen children (aged 1 month-14 years) with purulent meningitis and 12 children (aged 6 months-12 years) with aseptic meningitis were included into the study. Serum PCT concentration was measured on admission by immunoluminometric assay. Thirty healthy controls (aged 3 months-14 years) were also enrolled into the study. Serum PCT concentration was above 0.5 ng/ml in 14 out of 15 children with purulent meningitis (range 0.0-95.2 ng/ml; arrhythmetic mean--28.2 ng/ml). In all children with aseptic meningitis (range 0.0-0.3 ng/ml; mean--0.1 ng/ml) as well as in healthy controls (range 0.0-0.3 ng/ml; mean--0.1 ng/ml) serum PCT was below 0.5 ng/ml. CONCLUSION: Elevated serum PCT concentration in child with meningitis suggests bacterial aetiology. PMID- 11204323 TI - [Apolipoprotein E(ApoE)and tau protein in Alzheimer type dementia]. AB - In 45 patients meeting NINCDS-ARDRA criteria for probably diagnosis of Alzheimer disease (AD), ApoE genotype and tau protein level in cerebro-spinal fluid (CSF) were determined. Frequency of e4 allele occurrence in group of AD patients was 73.3% and showed high statistic significance in comparison with control group. Increase of tau protein level in CSF was also statistically significant. No correlation in ApoE allele and tau protein level in CSF was revealed. The authors emphasize the usefulness of tau protein level measurement and determination of ApoE allele in diagnosis of Alzheimer disease. PMID- 11204324 TI - [Early results of patient rehabilitation after anterior cruciate ligament reconstruction]. AB - In the Orthopedic Department of the Upper-Silesian Rehabilitation Center "Repty" in Ustron 54 patients have been rehabilitated after a plasty of the anterior cruciate ligament and transplantation of 1/3 middle part of the patellar ligament with two osseous blocks at each end. The rehabilitation was conducted according to the scheme worked out in our department. The results of the rehabilitation were assessed by the objective and subjective methods (for example the goniometric pendulum test, the modified Lysholm's scale, the WAS questionnaire). The patients had been divided randomly into two comparative study groups that were subject to exactly the same rehabilitation scheme, but one of the group was additionally provided with the impulsive magnetic field therapy. A satisfactory improvement was observed in both groups of patients. There was no significant advantage of additional treatment with the impulsive magnetic field. PMID- 11204325 TI - [Laparoscopic splenectomy with a postero-lateral approach in patients with idiopathic thrombocytopenic purpura]. AB - The aim of the study is presentation of operative technique and early results of laparoscopic splenectomy in 15 cases of idiopathic thrombocytopenic purpura (ITP) patients resistant to typical steroid therapy. There were 7 women and 8 men in age 16-58 years (mean 32.6 years). Preoperative investigations revealed accessory spleens in two patients. Platelets count at the time of qualifying patients to splenectomy varied from 7-35 g/L and after preoperative treatment (prednisone 1 mg/kg--6 patients, methylprednisone 25 mg/kg--5 patients, immunoglobulins 2.0/kg- 2 patients, immunoglobulins and methylprednisone--2 patients) varied from 36-205 g/L. Splenic length was from 8-17 cm. The lateral approach and 4-5 ports were utilized in all cases. Pneumoperitoneum with value of 12-14 mmHg of carbon dioxide was created using an open technique. First step of the procedure was to free spleno-colic ligament, then spleno-reno attachment. In all cases the hilus artery, vein and short gastric vessels were clipped and divided by Endo GIA stapler 30 or 60 mm and clips. Spleens were removed from the abdomen cavity in the plastic bag after manual/forceps crushing inside the bag. Intraoperative bleeding occurred in 2 patients (20%). Blood loss was about 800 and 1000 ml respectively. The mean operative time was 170 min (140-300 min). Spleen weight was 210 g average. In 3 cases conversion to open approach was needed because of injury of splenic vessels (2 pts.) and difficulty in removing spleen--in 1 patient. Post operative course was uneventful in every 10 patients. Mean hospital stay was 5.8 days. Increase in platelet count was observed in 14 patients on the second postoperative day to 60-291 g/L. One patient did not response as expected. No early postoperative complications were observed. CONCLUSION: Laparoscopic splenectomy may be considered as a safe and feasible procedure in selected patients with ITP without long-term improvement after typical conservative treatment. PMID- 11204326 TI - [Analysis of general and hemorrhagic complications after treatment of acute proximal deep venous thrombosis of the legs treated with anticoagulants, streptokinase and thrombectomy]. AB - The aim of the study was to present general and haemorrhagic complications in 164 patients with acute DVT in ilio-femoral segment treated with different methods of pharmacological (heparins, streptokinase) and surgical (venous thrombectomy with temporary arterio-venous fistulae) therapy. There were no fatal complications in 48 UH or LMWH treated patients. One patient bled from stress stomach, one developed intramuscular haematoma, one mild pulmonary embolism and one rise of body. Among 84 patients treated with SK five fatal bleeding complications were recorded. From other non fatal complications we recorded one GI bleeding, one splenic rupture and three massive intramuscular haematoma. Three patients died in the early post thrombectomy period. Non fatal complications included one wound haematoma, two wound infection and one with marginal necrosis. The use of LMWH or UH treatment in acute ilio-femoral venous thrombosis is save as the frequency of massive bleeding and serious general complications is rather low. Fatal haemorrhagic episodes are the major hazards of thrombolytic therapy. Venous thrombectomy with temporary arterio-venous fistula may provide a good chance for treatment of acute proximal DVT associated with complete occlusion of the lumen of affected veins in patients with severe ischemic venous thrombosis or with contraindications to heparin treatment. PMID- 11204327 TI - [Single sigmoidoscopy for screening of colorectal cancer]. AB - Once-only sigmoideoscopy of person aged 57 is successful and safe method of screening of colorectal cancer. However acceptance of invitation to screening was about 25%. Because of that we postulated once-only sigmoideoscopy screening for patients aged 57 hospitalized from other than digestive tract neoplasms causes. PMID- 11204328 TI - [Care of the frail elderly in population studies]. AB - The paper is one of the publications presenting the Polish part of the study on the EASY-Care questionnaire. The study was carried out as the multi-centre project "Supporting Clinical Outcomes in Primary Care of the Elderly". The EASY Care Questionnaire is an instrument to assess the health care needs and social situation of older people for use in primary care. OBJECTIVES: To identify the main providers of help to the frail community-dwelling elderly people aged 75 years and over. DESIGN: Cross-sectional questionnaire study, survey. SETTING: Community-dwelling elderly people living in the administrative borders one of the community health care centres in Bialystok-city. PARTICIPANTS: 117 randomly selected people aged 75 years and over; the interviewers were doctors and nurses, serving the studied area. MEASUREMENTS: Elderly Assessment System EASY-Care, version 1997,98. RESULTS: 81 persons of the studied group (69.2%) were ADL dependent. Most of the elderly people in need of care were women, more often with the suspicion of depression and with cognitive impairment. Most of the caregivers (80%) of the frail community-dwelling elderly people 75 and over were family members living together (42%), living apart (21%) or it was wife/husband (17%). Almost 10% of the ADL-dependent elderly had no carer at all. The category of carers fulfilling all of the needs of the care recipient were more often the spouse. The role of the public care providers was marginal. CONCLUSIONS: The family is still the basic source of support and the central element in the care system for the elderly in Poland. The family is insufficiently supported by formal and informal carers. PMID- 11204329 TI - [Acute hepatitis caused by cytomegalovirus]. AB - Cytomegalovirus (CMV) is widespread. In most cases CMV infection is asymptomatic. The most significant clinical syndrome is mononucleosis and hepatitis. We report a case of 38 old woman with CMV hepatitis associated with erysipelas. PMID- 11204330 TI - [Argon plasma coagulation in a patient with early diagnosis of gastric carcinoma]. AB - Argon plasma coagulation (APC) has been introduced for the local endoscopic treatment of gastrointestinal malignancy recently. It is mainly used as a palliative therapy, especially in case of stenosis. Despite a lot of publications concerning APC the clinical usefulness of this method in a small malignant tumors remains unclear. The patient with early diagnosed carcinoma of gastric, efficiently treated using argon plasma coagulation is described. PMID- 11204331 TI - [A patient with abdominal actinomycosis--diagnostic problems]. AB - The difficulties in diagnosis of abdominal actinomycosis are presented. Clinical manifestations and colonoscopy suggested malignancy. Final diagnosis was made on the basis of pathological assessment of resected sigmoid. Authors underline that in case of "negative" pathomorphological results of material obtained during endoscopy from lesions suspected, benign disease should be consider including anctinomycosis and intraoperative pathomorphological examination should be performed. PMID- 11204332 TI - [Use of cefuroxime axetil in clinical practice]. AB - This study summarizes the actual recommendations for cefuroxime axetil treatment in dermatology and general medicine. These include the well known clinical efficacies in therapy of upper and lower respiratory tract infections, genitourinary tract infections and skin and soft tissue infections, but also connective tissue diseases, such as morphea and SCLE. Though the immunomodulatory activity of the drug should be established by further controlled studies, there are some limited literature data, which show the modulatory effect of cefuroxime axetil on the lymphocyte proliferation and the production of selected cytokines. PMID- 11204333 TI - [Interactions between food and drugs. 1. Malabsorption]. AB - The paper overviews food-drug interactions. The part 1 reviews the interactions of foods with the many different agents which occur at the level of absorption, considering the mechanisms involved. The food-drug interactions can cause an increase, decrease, or delay in the bioavailability of the drugs. There is an aspect of therapy which may have an important clinical repercussion, which it must not be forgotten. PMID- 11204334 TI - [Interactions between food and drugs. 2. Disturbances of drug metabolism and synergistic mode of action]. AB - The paper overviews food-drug interactions. The part 2 reviews the interactions of foods with the drugs which occur at the level of metabolism. Concomitant intake with food increases or decreases the concentrations of many agents in humans. The effect seems to be mediated mainly by suppression of the cytochrome P450 in the liver and in the small intestine wall. This results in a diminished first pass metabolism with higher bioavailability and increased maximal concentrations of substrates of this enzyme. To avoid the interactions many drugs should not be taken with the meal and citrus juices, particularly grapefruit juice. PMID- 11204335 TI - [Munchausen's syndrome by proxy--a malignant form of child abuse]. AB - Munchhausen syndrome by proxy is a malignant form of child abuse in which illness in a child is fabricated and/or induced by a parent. It can result in serious illness and even death of the child and it is difficult to detect. The authors give a significant amount of literature examples. They try to find out the difference in ways of hurting by perpetrators. Various types of personalities and emotional disturbances in Munchhausen on proxy syndrome are shown. Child maltreatment and Munchhausen by proxy syndrome need to be part of the differential diagnosis when the clinical picture is atypical or does not appear medically plausible. PMID- 11204336 TI - [Hyperprolactinemia--unappreciated clinical problem]. AB - In the study, in concise way, actual knowledge concerning hyperprolactinemia was presented. Its causes, clinical symptoms, diagnostic proceeding, methods of treatment and prognosis were discussed. PMID- 11204337 TI - [Primary hyperparathyroidism treated surgically]. AB - Primary hyperparathyroidism is a systemic disease, more and more frequently recognized-concerning 1 to 3% of the population. Statistically appears in 1 of 1000 adults, with significant advantage of women. In Poland every year about 30 new cases are noticed and incidence increases with an age. In spite of significant advance of the knowledge, it still makes a lot of diagnostic troubles. It appears to be non-specific illness, characterised by just one symptom, mainly urolithiasis, sometimes chronic ulcer disease, chronic pancreatitis, arterial hypertension, disorders of the movement or psychic disorders. Parathyroid adenoma which is the main reason of the disease is usually single and small, multiple and bigger ones are found exceptionally. In about 2% of cases they are localized in mediastinum. In the article the basic symptoms, diagnostic and therapeutic problems were shown, especially concerning surgical treatment which is safe, radical and efficacious method when performed by experienced surgical team and the conduct from choice on primary and secondary hyperparathyroidism. PMID- 11204338 TI - [Anetoderma--a clinical and therapeutic problem]. AB - Current views on etiopathogenesis of anetoderma have been presented on the grounds of literature data. Disorders of elastin metabolism are distinctive for the disease causing elastin fibres becoming disintegrated and atrophied. Apart from mechanism of anetoderma plaques evolution clinical observation and full diagnostication of systemic collagenosis seems to be important. Despite of numerous therapeutic trials it appears that medication of anetoderma lesions is inefficacious. PMID- 11204339 TI - Recent life events, social adjustment, and suicide attempts in patients with major depression and borderline personality disorder. AB - This study investigated the impact of recent life events and social adjustment on suicide attempter status in 34 patients with major depression, 24 patients with borderline personality disorder, and 22 patients with co-morbid major depression and borderline personality disorder. Suicide attempters reported more recent life events and scored lower on a measure of social adjustment in their families and overall social adjustment, compared with non-attempters. Borderline disordered and borderline or depressed patients were more likely to have attempted suicide than patients with major depression only. Recent life events did not predict attempter status. Lower social adjustment in the immediate family and lower overall social adjustment were predictive of suicide attempter classification, regardless of diagnosis. Borderline disordered patients low on overall social adjustment were over 16 times more likely to have attempted suicide than patients diagnosed with major depression only. Recent life events may elevate suicide risk in groups already at high risk for suicide completion, whereas high levels of social adjustment may be protective against stress-related suicidal behavior. PMID- 11204340 TI - Recollections of conflict with parents and family support in the personality disorders. AB - This study examined the relationships between personality disorders and retrospective reports of family support and conflict with parents. Participants were 798 United States Air Force recruits who were participating in a larger program of research on the peer assessment of personality disorders. Correlational analyses revealed consistent but modest associations between personality disorder features and both measures of family adversity. Borderline, antisocial, and paranoid features maintained small, unique associations after controlling for the general component of personality disorder. Further analyses, however, showed that differences among the correlations between personality disorder traits and family adversity measures account for little explained variance. In general, it does not appear that individual personality disorders have unique relations with retrospective reports of family adversity. Instead, the relation between personality disorders and family adversity seems to depend on a component common to all personality disorders. PMID- 11204341 TI - Emotional responses in patients with borderline as compared with avoidant personality disorder. AB - The aim of this study was to assess psychophysiological affect correlates, in addition to the usual self-report in borderline personality disorder (BPD) compared with avoidant personality disorder (APD) and normal controls (NCs), when responding to standardized experimental stimuli. In 24 BPD female patients, 23 APD female patients, and 27 female NCs, skin conductance response (SCR), heart rate (HR) change, and startle response were recorded while the subjects viewed slides with emotional content. Neither the self-report nor the psychophysiological data supported the hypothesis that affective responses of BPD individuals are generally stronger than those with APD. BPD patients showed no potentiation of the affective modulation of the startle reflex and their electrodermal reactivity was lower than in either the APD subjects or the NCs. The hypothesis of a general affective hyperresponsivity could not be confirmed. Low somatic arousal in BPD can interfere with the anticipation of signal stimuli and may explain the exaggerated openness borderline personalities show to stimuli, particularly in interpersonal situations. PMID- 11204342 TI - A study of temperament and personality in anorexia and bulimia nervosa. AB - Although temperament and personality traits could influence the development and course of eating disorders, only a few studies examined the similarities and differences in personality between anorexia and bulimia nervosa. We compared 72 patients with DSM-IV eating disorders and 30 healthy controls. Dimensions of personality and personality disorders were evaluated with the Eysenck's EPQ, Cloninger's TCI, and the SCID-II questionnaires. The rates of impulsivity and clinical features were evaluated using specific rating scales. A comorbid personality disorder was found in 61.8% of patients with eating disorder. Avoidant personality disorder appeared was relatively common in anorexia nervosa restricting type; borderline personality disorder was most frequent in bulimia nervosa and the binge eating-purging type of anorexia nervosa. From a dimensional perspective, anorexic patients presented high scores in the dimension of persistence. Higher harm avoidance and impulsivity was found in bulimic patients. The overall eating disorders group presented high scores in neuroticism and low scores in self-directedness. Eating disorder patients have heterogeneous features of temperament and personality traits. Cluster C personality disorders seem more common in anorexia nervosa restricting type and impulsive personality features are associated with bulimic symptoms. Impulsivity seems to be a key aspect of temperament of bulimic patients, whereas anorexic symptoms are linked to persistent temperament traits. PMID- 11204343 TI - The developmental profile: preliminary results on interrater reliability and construct validity. AB - This study presents the preliminary results of research into the interrater reliability and construct validity of the Developmental Profile (DP). In the DP a number of developmental lines, such as Object-Relations, Self-Images, and Problem Solving Capacities, are assessed and classified according to the level of functioning. A total of 108 profiles were assessed, drawn from three different categories of patients. The weighted kappa values for interrater reliability were sufficient. On the adaptive level, but also on the maladaptive levels Symbiosis and Resistance, significant differences were found between psychiatric patients, "normal controls" (dental patients) and somatic patients. No differences were recorded between the latter two groups. The conclusion is that the DP is a promising instrument, of which the reliability and validity has to be further investigated in order to contribute to scientific support for psychodynamic theory formation. PMID- 11204344 TI - Hypervigilance in borderline disorder: a test with the emotional Stroop paradigm. AB - The hypothesis of cognitive theories of hypervigilance for signs of danger in Borderline Personality Disorder (BPD) was tested with the emotional Stroop task. BPD patients (n = 15), Cluster C personality disorder (PD) patients (n = 12), and nonpatient controls (n = 15) diagnosed with SCID-I and SCID-II interviews color named emotional and nonemotional words presented in three colors on a personal computer screen, first in a subliminal condition (words presented for a very short, individually calibrated time followed by a mask to prevent conscious recognition of the word) and then in a supraliminal condition. Four classes of negative words were used, including three classes of BPD-specific words (negative views of others, sexual abuse-related words, negative self-descriptors) and one class of general negative words that was unrelated to BPD pathology. In contrast to the nonpatient controls, both BPD and Cluster C patients showed interference caused by supraliminally presented emotional words. There was no difference between the clinical groups and there was no evidence for specificity of the effect for certain stimulus classes. The subliminal Stroop failed to yield any significant effect. Results are interpreted as evidence for the presence of a relatively crude hypervigilance for any emotionally negative stimulus in both BPD and Cluster C PDs. PMID- 11204345 TI - Genetic variation of the glutamate transporter EAAT2 gene and vulnerability to alcohol dependence. AB - Glutamate-mediated excitatory pathways play an important role in the pathogenesis of alcohol dependence. The present association study tested the candidate gene hypothesis that variation of the gene encoding the astroglial glutamate transporter EAAT2 confers vulnerability to alcohol dependence. Genotypes of a silent G603A nucleotide exchange in exon 5 of the EAAT2 gene were assessed in 565 subjects of German descent, comprising 342 alcohol-dependent subjects and 223 control subjects. Two more homogeneous subgroups of alcoholics were selected: (1) 112 alcoholics with a history of alcohol withdrawal seizure or delirium; and (2) 54 alcoholics with an antisocial personality disorder. The Tridimensional Personality Questionnaire was applied to assess personality dimensions in 106 alcohol-dependent males. The allele frequencies of the G603A polymorphism did not differ significantly between the control subjects and either the entire sample of alcoholics or the alcoholics with severe physiological withdrawal symptoms. Without correction for multiple testing, there was a significant increase of the frequency of the A603 allele in the antisocial alcoholics compared with either the control subjects [chi2 = 4.587, 1 degree of freedom (df), P = 0.032] or the alcoholics without ASPD (chi2 = 4.968, 1 df, P = 0.026). The personality trait of Harm Avoidance was significantly lower in alcoholics carrying the A603 allele compared with those lacking it (U-test; P = 0.009). These two consistent lines of evidence suggest that genetic variation of the EAAT2 gene confers vulnerability to risk-taking behavior in alcoholics. PMID- 11204346 TI - An association between a polymorphism of the tryptophan hydroxylase gene and aggression in schizophrenia and schizoaffective disorder. AB - Serotonergic pathways have been implicated in impulsive and aggressive behavior. Polymorphisms in the regulatory region of the serotonin transporter (5-HTT), in intron 7 of the tryptophan hydroxylase (TPH) gene and in the MAOA gene were previously reported to be associated with mood and anxiety disorders, impulsivity and aggression. In this study, we analyzed these polymorphisms in men and women with schizophrenia or schizoaffective disorder (n = 84) who met our criteria for violence (history of two or more assaults on others) or nonviolence (no history of either assaultive or threatening behavior). In males, a modest association between TPH genotype and history of violence (chi-square test = 6.703, degrees of freedom = 2, P = 0.035) was not statistically significant after correction for multiple comparisons (corrected P = 0.21). The TPH L allele was more frequent in violent males (chi-square = 5.323, degrees of freedom = 1, P = 0.021) but this difference also failed to withstand correction (corrected P = 0.126). No significant associations were found for either the 5-HTT or MAOA polymorphisms in males or females. These results tend to support previous reports by New et al. (1996; 1998) of an association between the TPH L allele and impulsive aggression in males with personality disorder, but larger studies are needed. PMID- 11204347 TI - Suicidal behavior in patients with schizophrenia is related to COMT polymorphism. AB - A common functional polymorphism that results in a three- to four-fold difference in catechol-O-methyltransferase (COMT) enzyme activity has been related to psychiatric disorders such as ultra-ultra rapid cycling bipolar disorder, drug abuse and alcoholism (Lachman et al., 1996a; Karayiorgou et al., 1997; Vandenbergh et al., 1997; Papolos et al., 1998; Tiihonen et al., 1999). Several studies have also reported associations between the allele encoding the low enzyme activity COMT variant (L allele) and other-directed aggression (Strous et al., 1997; Lachman et al., 1998; Kotler et al., 1999) in schizophrenic and schizoaffective patients. The current study investigated whether the COMT L allele is also associated with suicide attempts in schizophrenic and schizoaffective patients. COMT genotypes were determined and history of suicide attempts was retrospectively investigated in a Finnish sample (n = 94) and a US sample (n = 54). Significant associations were observed between COMT genotype and suicide; specifically, history of violent suicide attempts. The COMT L allele was more frequent in subjects who had attempted suicide by violent means. These associations were significant in males but not females. These findings support a common neurobiological substrate for self- and other-directed aggression, and suggest that catecholaminergic alterations may contribute to these behaviors in schizophrenic and schizoaffective patients. PMID- 11204348 TI - Pleiotropy of the serotonin transporter gene for seasonality and neuroticism. AB - Pleiotropy refers to the ability of a single gene to influence multiple traits. A polymorphism in the regulatory region of the serotonin transporter gene (5 HTTLPR) has previously been found to be associated both with the personality trait of neuroticism and with seasonal changes in mood and behavior, or seasonality. Hypothesizing that the contribution of the serotonin transporter gene to seasonality is specific, i.e. independent of neuroticism, we measured 5 HTTLPR genotypes and both psychological traits in 236 healthy volunteers. The results indicated that the 5-HTTLPR contributions to variation in the two traits are largely independent; approximately three-quarters of the effect of the gene on seasonality are not related to its effects on neuroticism. Moreover, the gene has a larger effect on the covariation between neuroticism and seasonality than it does on either trait alone. Sibling-pair analysis confirmed that the effects of the 5-HTTLPR are due to genetic pleiotropy rather than population stratification. PMID- 11204349 TI - Non-association of dopamine D4 and D2 receptor genes with personality in healthy individuals. AB - Recently, different research groups reported conflicting results with regard to an association of dopamine 4 receptor (DRD4) genotypes and the personality dimension of novelty seeking (NS). High scores for NS seemed to be associated with long alleles of a DRD4 polymorphism. Furthermore, an association between personality traits and the dopamine 2 (DRD2) receptor gene was reported. NS and persistence (PS) high scores seemed to be associated with alleles of DRD2. We examined 109 (78 female and 31 male) normal healthy individuals using Cloninger's Temperament and Character Inventory (TCI) in order to replicate these findings. We genotyped a 48 base pair variable number of tandem repeats (from two to eight repeats) polymorphism in the third exon of DRD4 and a Cys311Ser polymorphism in exon 7 of DRD2. We tested alleles and genotypes of DRD4 (allele 7 absent or present; genotype 4,4 versus 4,7), and Ser/Cys and Cys/Cys genotypes of DRD2 for associations with TCI values. NS and the alleles and genotypes of DRD4 did not show any association. In associating the genotypes of DRD2 with TCI scales (NS, harm avoidance, reward dependence and PS), we also found no association. Recent findings associating NS with DRD4 could not be replicated. With regard to DRD2, we tested a different polymorphism as published recently and could not find an association of TCI scales with the gene. The present results therefore do not provide evidence that the DRD2 and DRD4 receptor genes contribute a common and relevant effect to personality traits. PMID- 11204350 TI - A contribution to genome-wide association studies: search for susceptibility loci for schizophrenia using DNA microsatellite markers on chromosomes 19, 20, 21 and 22. AB - As an initial step for genome-wide association studies, we sought an association between schizophrenia and 34 microsatellite markers on chromosomes 19, 20, 21 and 22 by a case-control design. The samples examined for an association were 168 schizophrenic patients and 146 control subjects in the Japanese population. The allele distribution of the 34 loci differed significantly between Japanese and French populations. Significant deviation from the Hardy-Weinberg equilibrium was observed at D19S209 and D21S1256 in the control subjects. Case-control comparisons of the initial screening revealed a significant difference in allele frequency at D20S95 and a trend of difference at D20S118. To confirm these possible associations, additional samples consisting of 110 schizophrenic patients and 116 control subjects were examined, and an association between D20S95 and schizophrenia was confirmed (corrected P value after Bonferroni correction, 0.00035). D20S95 is located close to the gene (CHGB) encoding chromogranin B. These findings suggest that CHGB could be an important candidate gene involved in the development of schizophrenia. PMID- 11204351 TI - Lack of association in Japanese patients between neuroleptic malignant syndrome and a debrisoquine 4-hydroxylase genotype with low enzyme activity. AB - Decreased activity of debrisoquine 4-hydroxylase (CYP2D6), which participates in hepatic metabolism of several frequently used neuroleptics and antidepressants, is inherited as an autosomal recessive trait through polymorphic CYP2D6 gene alleles. In eastern Orientals, a C --> T substitution at nucleotide 188 (Pro34Ser) is primarily responsible for decreased ability to metabolize CYP2D6 substrates. We therefore studied a possible association between neuroleptic malignant syndrome (NMS) and the C188T mutation. We examined the frequency of the C188T mutation by polymerase chain reaction and restriction fragment length polymorphism analysis in 36 Japanese patients previously diagnosed with NMS and 107 neuroleptic-treated schizophrenic patients with no NMS history. The C188T allele frequency was 0.417 in NMS patients and 0.463 in patients without NMS. No significant allele or genotype associations were observed. We cannot conclude that low CYP2D6 activity genotype causes susceptibility to NMS in Japanese patients. PMID- 11204352 TI - Association study of a cannabinoid receptor gene (CNR1) polymorphism and schizophrenia. AB - Cannabis can induce schizophrenic-like symptoms in healthy individuals. A principal active ingredient of cannabis, delta-9-tetrahydrocannabinol, acts in the brain on a specific receptor, termed the cannabinoid receptor 1 (CNR1). The human gene for CNR1 is mapped to chromosome 6q14-15, and linkage studies have produced evidence for a schizophrenia-susceptibility locus in this region. To explore a possible role for CNR1 in the pathogenesis of schizophrenic disorders, we used an association study to genotype the CNR1 polymorphism for 127 schizophrenic patients and 146 control subjects. The results demonstrate no association between CNR1 genotypes and schizophrenic disorders (P = 0.409), with these negative findings suggesting that, for Chinese populations, the (AAT)n triplet repeat in the promoter region of the CNR1 gene is not directly involved in the pathogenesis of schizophrenic disorders. PMID- 11204353 TI - Oesophageal candidosis in intensive care patients. AB - We conducted upper intestinoscopies in 124 intensive care patients, six of whom had oesophageal candidosis. Of these, two also had Candida plaque in the stomach. The patients at the intensive care unit (ICU) had a mean Apache-II score of 26.7; whereas the score was 29.5 in patients with Candida oesophagitis. A significant increase of Candida antibodies was found in 59 of 124 patients (47.6%), including all patients with oesophageal candidosis. Presumably, mycotic infections of other sites were present. The severity by which mucous membranes were affected correlated well with microscopically evident invasiveness. PMID- 11204354 TI - Identification of medically important Aspergillus species by single strand conformational polymorphism (SSCP) of the PCR-amplified intergenic spacer region. AB - The amplified 5.8S RNA coding DNA with the neighbouring internal transcribed spacers ITS I and ITS II (ITS I--5.8S rDNA--ITS II) of 27 culture collection strains of Aspergillus fumigatus, Aspergillus flavus, Aspergillus nidulans, Aspergillus niger, and Aspergillus terreus were investigated by single strand conformational polymorphism (SSCP) analysis. All strains showed a polymerase gel electrophoresis (PCR) product of 0.6 kb. Separation of DNA single strands of the PCR product in an acrylamide-bisacrylamide gel containing formamide SSCP resulted in individual patterns for each of the species. A minor variability within the species A. fumigatus and A. flavus did not affect the correct species identification. The results were confirmed when investigating 55 wild strains from patients and the environment. It is concluded that the analysis of the amplified ITS I--5.8S rDNA--ITS II region by SSCP allows the differentiation of the medically most relevant aspergilli. As the method does not require morphologically fully developed fungal colonies, it yields species diagnosis faster than the conventional macroscopic and microscopic identification. PMID- 11204355 TI - Strain specificity of yeasts isolated from different locations of women suffering from vaginal candidosis, and their partners. AB - Sexual partners often harbour identical yeast strains in the vagina, in the orointestinal tract and in semen in cases of recurrent vulvovaginal candidoses. Specimen were collected from vagina, oral cavity and faeces of the patients, and from semen, oral cavity and faeces of their male partners. Mycological cultures were grown on Sabouraud glucose-agar and, if positive, specified by Candida-ID Agar (BioMerieux), by formation of chlamydospores on rice agar, and by biochemotyping with the System Walkaway (Dade) or the API-32C system (BioMerieux). A polymerase chain reaction finger-printing technique with the T3B oligonucleotide as single primer was used for strain typing. Candida albicans was isolated from the vagina of 18 out of 21 patients, the vagina of one patient harboured a strain of Candida glabrata. The cultures obtained from vagina, oral cavity and faeces were genetically identical in 12 patients. From the partners of 15 patients C. albicans was cultured in at least one of the clinical samples. Identical strains were observed for eight of 15 couples, whereas four of these identical strains were cultured from semen. Further prospective investigations will prove whether a consequent treatment of both partners will eradicate identical yeast strains and will be able to improve the results of treatment in such women. PMID- 11204356 TI - Acute vaginal candidosis model in the immunocompromized rat to evaluate delivery systems for antimycotics. AB - A rat model of vaginal candidosis, suitable for screening new antifungal compounds or novel formulations was developed and validated. Two strains of Candida albicans, different inoculation schedules, quantitative assays for fungal burden and the necessity for immunosuppression were tested. The infection was evaluated clinically and histologically by fungal counts from the vaginal discharge. The animals without immunosuppression did not sustain the infection beyond 2-3 days, however, after immunosuppression with cyclophosphamide, the infection can be maintained for about 2 weeks and is suitable for the testing of topical antifungal therapies. PMID- 11204357 TI - In vitro susceptibilities of Paracoccidioides brasiliensis yeast form to antifungal drugs. AB - A total of 12 Paracoccidioides brasiliensis yeast form strains, including clinical and environmental isolates, were tested for their susceptibilities to amphotericin B, ketoconazole, fluconazole, and itraconazole. The tests were determined using a broth macrodilution procedure. In general, there was a remarkable homogeneity of results for all strains, and comparable MICs were found for environmental and clinical isolates. PMID- 11204358 TI - A new species, Phialophora europaea, causing superficial infections in humans. AB - A new species, Phialophora europaea, member of the P. verrucosa complex, is introduced. It is distinguished from existing species by reduced, flaring phialidic collarettes and inability to assimilate melibiose as sole source of carbon. Analysis of ITS1 and 2 rDNA of six strains attributed to the species show it to be clearly individualized. All strains originated from cutaneous and nail infections of humans in North-western Europe. A key to morphologically similar taxa is provided. PMID- 11204360 TI - Case report and review. Onychomycosis due to Candida parapsilosis. AB - We report a case of onychomycosis with melanonychia due to Candida parapsilosis alone. Candida parapsilosis is now identified in the great majority of candidal onychomycosis, mainly in association with other yeasts. The criteria allowing the distinction between invasion and colonization, the risk factors and the treatment of C. parapsilosis onychomycosis are discussed. PMID- 11204359 TI - Usefulness of 1% terbinafine HCl (Lamisil) cream for hyperkeratotic-type tinea pedis and its transfer into the horny layer. AB - The usefulness of 1% terbinafine HCl (Lamisil) cream for hyperkeratotic-type tinea pedis and its transfer into the horny layer were evaluated. Of the 36 patients enrolled in the study, 35 were retained for analysis and one was excluded due to inappropriate drug application. Hyperkeratotic-type tinea pedis was classified into three types: true hyperkeratotic-type, partial hyperkeratotic type, and quasi-hyperkeratotic type. The overall clinical improvement rate was 95.5% (100% for true-, 80% for partial- and 96.2% for quasi-hyperkeratotic type). The overall fungal eradication rate was 88.6% (75% for true-, 100% for partial- and 88.5% for quasi-hyperkeratotic type). The overall efficacy rate was 88.6% (75% for true-, 100% for partial- and 88.5% for quasi-hyperkeratotic type). No adverse reactions were reported. Drug concentrations in the horny layer were 170.3, 228.5 and 249.2 ng mg-1, respectively, 2, 4 and 12 weeks after starting the treatment. These concentrations are more than 50,000 times higher than the minimum inhibitory concentrations of terbinafine for dermatophytes. These findings indicate that terbinafine HCl (Lamisil) cream is very useful for refractory hyperkeratotic-type tinea pedis when administered alone. The pharmacokinetic data also support the clinical and mycological findings. PMID- 11204361 TI - Further comments on Malassezia species from dogs and cats. PMID- 11204362 TI - Should a patient with a brain tumor receive anticoagulation for a thromboembolic event? PMID- 11204363 TI - Radiofrequency ablation of the pulmonary veins: can it stop atrial fibrillation at its source? AB - Recent work from France indicates that many cases of atrial fibrillation arise from foci of rapidly firing cells, most of which are located not within the atria but within the pulmonary veins. Armed with this new knowledge, we are pursuing strategies of permanently preventing atrial fibrillation by destroying these foci using radiofrequency ablation. PMID- 11204364 TI - An elderly woman with drug-induced coma in winter. PMID- 11204365 TI - Diagnosing interstitial lung disease: a practical approach to a difficult problem. AB - Interstitial lung disease has a variety of causes: environmental, infectious, autoimmune, and drug-related. Accurate diagnosis is essential because the prognosis and treatment of the disease varies widely depending on the cause. However, the respiratory symptoms and pulmonary radiographic picture of these various causes of interstitial lung disease are often similar, making the diagnosis of its cause confusing and frustrating. The practical, algorithmic approach to diagnosis outlined here identifies key diagnostic clues in the patient's history, physical exam, and radiographic findings. PMID- 11204366 TI - Heart failure disease management: a team approach. AB - Patients with heart failure do better if they are treated in a formal heart failure disease-management program than if they receive standard care: their hospitalization rates and costs of treatment are lower, and their functional status is higher. The programs feature close coordination between primary care givers, subspecialty consultants, and nurses with specialty training in the nuances of heart failure management. Aggressive medical therapy must be coupled with patient education and rapid response to early identified problems. This article reviews the principles of heart failure disease-management programs and cites evidence that they are beneficial. PMID- 11204367 TI - What the internist needs to know about infertility. AB - Primary care physicians can manage two thirds of cases of suspected infertility. Assisted reproductive technology can help in many cases of pelvic adhesive disease, although the effectiveness of these procedures declines significantly with patient age. Testing for ovarian reserve is an important first step for many patients who are considering infertility treatment. Some causes of infertility are associated with significant medical problems such as diabetes and abnormal lipids; these should be assessed and a long-term management plan implemented. PMID- 11204368 TI - Spiral CT for lung cancer screening: is it ready for prime time? AB - Low-dose spiral computed tomography (CT) shows promise as a screening test for lung cancer, as it detects many more malignant pulmonary nodules than does standard plain radiography of the chest. Yet until more data are available we need to temper our enthusiasm. No studies have yet determined if using low-dose spiral CT as a screening test will lead to lower mortality rates. This paper reviews the issue of lung cancer screening and low-dose spiral CT. PMID- 11204369 TI - Preventive medicine and screening. PMID- 11204370 TI - Low-dose spiral CT for lung cancer screening. PMID- 11204372 TI - At a glance. Reducing tobacco use: a report of the Surgeon General--2000. PMID- 11204371 TI - Should all college-bound freshmen receive meningococcal vaccine? PMID- 11204373 TI - Management of advanced/metastatic prostate cancer: 2000 update. AB - Over the past several years, the clinical presentation of prostate cancer has evolved so that more patients than ever before are presenting with clinically localized disease. However, a significant number of men continue to present with locally advanced or metastatic prostate cancer, or go on to develop metastasis after failing local therapies. Despite our better understanding of the biological principles and newer therapies, metastatic prostate cancer remains a lethal disease. Androgen ablation continues to be the first, most effective line of treatment for advanced/metastatic prostate cancer. Newer chemotherapy combinations with increasing activity are being identified in hormone-resistant prostate cancer. Based on novel targets, new treatment strategies are being developed and incorporated into clinical trials. Ultimately, the impact of these evolving treatments on advanced/hormone-resistant prostate cancer can best be assessed by well-designed phase III trials, many of which are now being launched or awaiting completion. PMID- 11204374 TI - Clinical trials referral resource. Current clinical trials in pediatric acute lymphoblastic leukemia. PMID- 11204375 TI - Aging and cancer. AB - The world's population is aging. Older age is associated with an increase in the incidence of cancer, especially cancer of the breast, lung, prostate, and colon. The management of older patients with cancer is biased by the simple fact of their chronologic age. Underscreening, understaging, less aggressive therapy, lack of participation in clinical trials, or no treatment at all reflect this bias. Although an age-related reduction in the physiologic function of many organs occurs with age, these are not contraindications to treatment with surgery, radiation therapy, or chemotherapy. Chronologic age alone should not be used as a guide for cancer management. Rather, physiologic function or existence of comorbid conditions should be major factors in determining treatment. As a result of the impending need for improved cancer management in older persons, a new subspecialty is evolving: geriatric oncology. This field stresses an important interaction between geriatricians and oncologists, development of research directed at the problems of cancer in older persons, and education at all levels with respect to cancer prevention, cancer detection, and cancer therapy. Physicians and oncologists need to be prepared for the projected increase of cancer in older persons. PMID- 11204376 TI - Pharmacology of antineoplastic agents in older cancer patients. AB - The fastest growing segment of the US population is the group over the age of 65 years. In the next 30 years, this group will comprise over 20% of the population. Because 60% of all cancers occur in this age group, there will be an expected rise in the total cancer burden. Emerging data will better guide the use of chemotherapy in older patients. Studies will be presented discussing the pharmacokinetics of a number of chemotherapeutic agents, with an emphasis on those that have come into use over the past few years. Many of these agents seem to have a beneficial therapeutic index, particularly in regard to elderly patients. There has also been a rising trend in the use of oral chemotherapy. This change was fueled by patient preferences, quality-of-life issues, and the need to decrease the cost of chemotherapy administration. Factors that must be taken into consideration with oral administration of chemotherapy include limitations of the saturability of absorption, patient compliance, and the pharmacokinetic and pharmacodynamic changes that occur in elderly patients. Interpatient variability and drug metabolism, particularly age-related changes in drug metabolism, have been studied. The cytochrome P450 system is particularly important in this context. Safe administration of chemotherapy requires careful attention to the physiologic changes occurring with age and dose adjustments to compensate for end-organ (i.e., renal and hepatic) dysfunction. These adjustments will be discussed for specific drugs. Complementary and alternative therapies will also be presented. PMID- 11204377 TI - Value of antigliadin antibodies (AGA) in latent coeliac disease (CD). AB - BACKGROUND: The term latent coeliac disease (CD) is applied to patients who were previously shown to have a normal jejunal mucosa on a free diet. The aim of this study was to determine whether a high AGA value in the serum of patients with coeliac symptoms can also be regarded by itself, without typical mucosal atrophy, as a marker of latent CD, as some authors suggest in relatives of celiac patients. METHODS: We observed 31 patients with suspected CD and pathological values of serum IgA ang IgG AGA. In all we performed intestinal biopsy, assayed antiendomisium antibodies (AEA) in serum, AGA IgA, IgG, and IgM in duodenal jejunal fluid and in some of the lymphocytcs CD3+ gamma/delta+ in the lamina propria of the intestinal mucosa. RESULTS: In this study only pathological values of serum AGA without mucosa atrophy don't seem to be markers of latent CD, but an aspecific allergic response. CONCLUSIONS: As shown by other authors serum AEA, intestinal fluid AGA IgM and lamina propria lymphocytes CD3+ gamma/delta+ seem markers of latent CD. PMID- 11204378 TI - [Head injuries in children. Considerations on 3,715 consecutive cases]. AB - BACKGROUND: The authors present their personal experience of 3715 cases of head injury in pediatric patients, occurring during the last three years (1997-1999), admitted to the Emergency ward at the "Anna Meyer" children's hospital in Florence. METHODS: A prospective study was made, starting from the evaluation made by the paediatric surgeon and following the subsequent diagnostic and clinical course. Depending on the severity of injury, this took the form of immediate discharge with a written sheet of instructions, "short observation" (up to 12 hours) in an Emergency ward and/or admission to neurosurgery or general medicine or to intensive care. The authors also analyse the diagnostic and instrumental tests carried out at the various stages (cranial X-ray, direct cranial CT, EEG) and the specialist consultations required (neurosurgery, neurology, paediatrics, resuscitation). Data for injured children transferred from other hospitals for neurosurgery were excluded from the study which only included patients examined primarily at our hospital. If admitted for more than 48 hours, a neurosurgical outpatient check-up was programmed one week later. In more severe cases, patients were admitted to day hospital between six months and one year later. RESULTS: Injuries were minor in 91% of cases and the age of patients ranged between 5 days and 14 years; moreover, 60% of the patients observed were male. Only 1.5% of cases seen in Emergency were admitted to hospital and 8.4% of all head injuries, with a total stay of between 1 and 6 days. There were 4 deaths in severely polytraumatised patients. There was only one case of firearm injury which was not fatal. Head X-rays were performed in 13.4% of patients showing evidence of fracture in 19.1% of cases. Direct cranial CT was performed in 10.2% of cases with pathological findings in 23.9% of cases. Neurosurgery was performed in one of the 5.9% patients admitted to hospital. The late sequelae to head injury included one case of epilepsy that occurred 7 months after injury. CONCLUSIONS: Anamnesis showed that the most frequent reason leading to head injury was lack of adult supervision and that the majority of severe injuries were caused by road accidents, both as pedestrians and as passengers. Lastly, the authors emphasise the importance of recognising and correctly treating so-called secondary cerebral damage, which has a non-immediate onset but is potentially severe, and identifying the risk factors for head injury in order to reduce the incidence and severity. PMID- 11204379 TI - Obstructive sleep apnea in children. AB - Obstructive sleep apnea (OSA) is a frequent albeit underdiagnosed condition in children, which if left untreated may lead to substantial morbidity. Important recent advances in the understanding of the pathophysiological mechanisms underlying OSA in children have been coupled with improved approaches towards the diagnosis and management of OSA. This review provides a detailed and current description of OSA in children, and focuses on the integrative elements necessary for increasing the awareness and diagnostic yield of the community practitioner. PMID- 11204380 TI - [Treatment of bronchial asthma in chidren]. AB - Asthma is a condition characterised by airways inflammation and bronchial hyperresponsiveness to specific and aspecific spasmogens associated with reversible airways obstruction. The bronchomotor tone is the result of an interaction between neurotransmitter release and local mediators. The efferent neurohumoral pathways to the muscular, vascular and glandular element include parasympathetic nerves, sympathetic nerves, and non-adrenergic non-cholinergic (NANC) neurotransmission. It is currently recognised that the alteration of these mechanisms can induce bronchial hyperresponsiveness that represents a characteristic feature of asthma. Asthma is common in children and its prevalence in this age group is increasing. The current therapy of asthma involves the use of anti-inflammatory drugs to control the underlying process (causal therapy) and the use of bronchodilators that provide rapid relief of bronchoconstriction (symptomatic therapy). The bronchodilators are represented by beta 2 adrenergic agonists, methylxanthines and anti-cholinergic drugs; the anti-inflammatory drugs are represented by corticosteroids, antileukotrienes and chromones. Other new therapies being studied include anti-immunoglobulin E, anti IL-5 agents, endothelin receptor antagonists, and others. PMID- 11204381 TI - Early onset neonatal sepsis due to Neisseria meningitidis B. AB - The onset of meningococcal infection in the first 72 hours after birth has only been reported on a few occasions; The authors describe a case where it was confirmed that the bacteria responsible, Neisseria meningitidis group B, grew in the newborn's blood and in the mother's lochia. The transmission mechanisms are also reviewed. PMID- 11204382 TI - [Major social diseases]. PMID- 11204383 TI - Hemisternotomy approach for aortic and mitral valve surgery. AB - After exploring several less invasive approaches for cardiac valve surgery, we have concluded that the partial upper sternotomy is the incision of choice for minimally invasive aortic and mitral valve surgery. From March 1997 to January 1999, 827 patients had cardiac valve surgery using this approach; 462 had mitral valve procedures and 365 had aortic valve procedures. Of those having mitral valve surgery, 87% had mitral valve repair. Aortic valve surgery included replacement with stented bioprostheses (38%), allografts (29%), and mechanical prostheses (10%); in addition, 23% had aortic valve repair. Operative mortality was 0.8%. Conversion to full sternotomy was necessary in 2.4%. Blood use was low with 80% of patients receiving no blood transfusions. We conclude that all primary mitral and aortic procedures can be accomplished safely via partial upper sternotomy. PMID- 11204384 TI - Minimally invasive direct access heart valve surgery. AB - We review our experience with minimally invasive direct access (MIDA) heart valve surgery in 518 patients. Two hundred fifty-two patients underwent MIDA aortic valve replacement (AVR) or repair and 266 underwent MIDA mitral valve repair or replacement. Among the 250 AVRs, 157 (63%) were men, aged 63.2 +/- 14.6 years, NYHA functional Class 2.4 +/- 0.8. The surgical approach was right parasternal in 36 (14%) or upper hemisternotomy in 216 (86%). There were four (2%) operative deaths. Perioperative complications included 14 (5.6%) reexplorations for bleeding, 7 (3%) chest wound infections, 5 (2%) strokes, and 1 (0.4%) external iliac vein injury. Follow-up was complete in 193 (77%) patients, with a mean follow-up of 12 +/- 8 months. Late complications included 2 (0.8%) nonfatal myocardial infarctions, 4 (2%) reoperations for, respectively, 2 pericardial complications, 1 paravalvar leak, and 1 infected valve. There were five (2%) late deaths from congestive heart failure, pneumonia, hemorrhage, aneurysm, and cancer. Mean follow-up NYHA Class was 1.4 +/- 0.6. For the 266 mitral patients, 145 (54.5%) were men, age 58.7 +/- 13.6 years, functional Class 2.3 +/- 0.5. The surgical approach was right parasternal in 195 (73%), lower hemisternotomy in 53 (20%), right submammary thoracotomy in 9 (3.4%), or full sternotomy through a small skin incision in 9 (3.4%). There were 2 (0.8%) operative deaths. Perioperative complications included 4 (1.5%) reoperations for bleeding, 4 (1.5%) strokes, and 5 (2%) wound infections, and 3 (1%) ascending aortic complications. Follow-up was complete in 202 (76%) patients with a mean follow-up of 9.5 +/- 6.4 months. Late complications included one (0.4%) nonfatal myocardial infarction and three (1%) reoperations all converting repairs to replacements. There were three (1%) late deaths from suicide, pneumonia, and sudden death, respectively. Mean follow-up NYHA functional Class was 1.3 +/- 0.5. We conclude that MIDA heart valve surgery is safe and effective for the majority of patients requiring isolated elective aortic or mitral valve surgery. PMID- 11204385 TI - Antagonist's view of minimally invasive heart valve surgery. PMID- 11204386 TI - Cardiac valve operations using a partial sternotomy (lower half) technique. AB - BACKGROUND AND AIM: Operations on cardiac valves are being performed more frequently through smaller incisions than traditional midline sternotomy. A variety of alternate incisions have been used, but most of the interest appears to focus on partial sternotomy. The purpose of the study was to review results using a partial lower sternotomy for cardiac valve operations. METHODS: A standard partial lower one-half or two-thirds sternotomy was used for cardiac valve operations in 112 patients. The sternum was divided transversely in the third or second intercostal space and vertically from that point through the xyphoid process. Standard instruments and retraction devices were used. This incision provided adequate exposure for even complex operations to be performed. Small cannulae were placed into the aorta and heart through the primary incision for cardiopulmonary bypass. Vacuum-assisted venous drainage was used. RESULTS: Seventy-four single valve operations were performed. There were 35 double valve and 5 triple valve operations (35.4%) performed. Operative mortality (5.3%) and major complication rates were comparable to full the sternotomy approach. CONCLUSIONS: Partial sternotomy (lower half) provides a smaller incision through which virtually all cardiac valve operations may be performed. Results achieved with this approach are similar to those associated with full sternotomy. The smaller incision is appreciated by patients. PMID- 11204387 TI - Three-year follow-up after port-access mitral valve surgery. AB - INTRODUCTION: After the promising early results with Port-Access mitral valve (MV) surgery, the mid-term results were evaluated. METHODS: Among 31 patients receiving this surgery, there were two subgroups (A and B). The 14 patients in group A (7 men, 7 women, 64.0 +/- 12.8 years, LVEF 0.62 +/- 0.118) received the procedure exactly as proposed by Heartport. The 17 patients in group B (6 men, 11 women, 63.0 +/- 11.48 years, LVEF 0.61 +/- 0.117) received a modified technique for a less complex procedure. The underlying diseases were MV insufficiency (n = 14), MV stenosis (n = 9), and combined MV disease (n = 8). One female patient had a partial atrial ventricular canal. RESULTS: Perioperative mortality was 3.2%. Survival at 39.0 +/- 6.3 months (median +/- SEM) was 93.5%. Two patients required intraoperative inotropic and mechanical support (intra-aortic balloon pump [IABP]). One of these two patients died on postoperative day 3 due to low cardiac output syndrome. All ther patients survived the procedure. Twenty-four patients underwent MV replacement, 7 patients received MV repair, and 1 patient received, in addition, ASD repair. In group B, operative time, ICU stay, and hospitalization was shorter. CONCLUSIONS: Good early results after Port-Access MV surgery were confirmed by equal mid-term results. The patients are satisfied with the surgical and the cosmetic results, however, Port-Access MV surgery still has to prove superior outcome compared to conventional MV surgery. In selected cases a true reduction of the surgical trauma is possible. PMID- 11204388 TI - Minimally invasive video-assisted mitral valve surgery: from Port-Access towards a totally endoscopic procedure. AB - Right thoracotomy is an alternative to mid-sternotomy for left atrium access. The Port-Access approach is an option that reduces the skin incision and obviates rib spreading. PATIENTS AND METHODS: From February 1997 until November 1999, 121 patients underwent mitral valve surgery through a right antero-lateral thoracotomy using the Heartport cardiopulmonary bypass (CPB) system. Mean age was 60 years (31-84). Most patients had normal ejection fractions and were in NYHA Class II or III. Seventy-five patients had valve repair (62%) and 46 (38%) had valve replacement. Pathologies were myxoid (n = 80), rheumatic (n = 30), chronic endocarditis (n = 5), annular dilatation (n = 3), sclerotic (n = 1), ingrowing myxoma (n = 1), and one closure of a paravalvular leak. RESULTS: Two patients had conversion to sternotomy for aortic dissection (one died) with the Endo-Aortic Clamp, and two others for peripheral vascular problems. One patient died at postoperative day 1 after reoperation for failed repair, another with double valve surgery on postoperative day 4 after two revisions for bleeding. Twelve underwent revision for bleeding (10%). Three had prolonged ICU stay for respiratory insufficiency. Two late valve replacements for endocarditis occurred. Echographic control revealed residual insufficiencies (grade 1-2) in two valvular repairs. There were neither paravalvular leaks nor myocardial infarcts. There were no cerebrovascular accidents due to embolic phenomena. Mean ICU and hospital stay were 2.1 and 8.7 days, with a major difference between the first 30 patients and those who followed. CONCLUSION: Port-Access mitral valve surgery can be a valid alternative to conventional sternotomy and seems to be an important improvement in minimally invasive cardiac surgery. PMID- 11204389 TI - Cardiac surgery: the future is minimal! PMID- 11204390 TI - Minimally invasive videoscopic mitral valve surgery: the current role of surgical robotics. AB - OBJECTIVE: Recently, the efficacy of video-assisted mitral valve surgery has been demonstrated. The evolution of this technology has been relatively rapid. In this article we review this development and predict the future of endoscopic and robotic-enabling technology for cardiac valve operations. METHODS: A new video assisted mitral valve operation is described and results discussed. The majority of each valve operation was done through assisted vision and near endoscopically. Cardiopulmonary bypass was established via femoral cannulation, and blood cardioplegic arrest induced using a new percutaneous, transthoracic cross-clamp. A 5 to 6-cm minithoracotomy was used in each patient. Videoscopy was helpful for suture placement, chord reconstruction, leaflet resection, knot tying, and valve ring or prosthesis positioning. A voice-activated robotic arm was used to direct the camera in many instances. RESULTS: Thus far a total of 110 patients have undergone this operation successfully with a 0.9% operative mortality. Our early series (N = 31), published with cost data, is reviewed in detail. Cardiopulmonary perfusion and cross-clamp times for all 100 patients were longer than for conventional sternotomy patients at 158 +/- 3.9 and 110 +/- 3.6 minutes, respectively, versus 121 +/- 4.6 and 90 +/- 4.6 (N = 105); however, there have been less complications. Operative, perfusion, and arrest times have fallen progressively to 144 +/- 4.5 and 90 +/- 4.5, respectively (N = 55 Aesop 3000 cases). Complex repairs and replacements have become routine with anterior leaflet pathology addressed. Bleeding, ventilatory times, blood transfusions, and hospital stay have been reduced. One patient required reoperation for a technically failed repair and two renal patients had late endocarditis. We have used voice-activated, robotic (Aesop 3000) assistance for camera control in 51 of these patients. This addition has decreased camera motion artifact and lens cleaning, while providing direct "cerebral-eye" tracking of instruments for the surgeon. We were the first in the United States to apply the DaVinci articulated wrist robot to do a complete mitral repair and have done multiple repair with this articulated wrist device. CONCLUSIONS: From this and other work reviewed, we conclude that video-assisted and computer-assisted robotic techniques are safe and may be the pathway to truly endoscopic mitral valve operations. We are encouraged regarding the use of this new technology for mitral valve operations. PMID- 11204391 TI - The micro-mitral operation comparing the Port-Access technique and the transthoracic clamp technique. AB - BACKGROUND: Several minimally invasive approaches to the mitral valve have been described, including parasternal incision and right anterolateral thoracotomy. MATERIAL AND METHODS: Since September 1996, 58 patients underwent minimally invasive mitral valve surgery at our institution through a right anterolateral minithoractomy. Two different techniques were used for institution of cardiopulmonary bypass (CPB) and aortic clamping: in the Port-Access group (group A) patients had femoro-femoral cannulation with a special arterial cannula to introduce an endoaortic balloon clamp (n = 23). The second group (group B) of patients underwent femoro-femoral CPB as well in combination with a specially designed transthoracic aortic clamp (Chitwood technique, n = 35). Patients were assigned to either technique in a nonrandomized fashion. Demographics were similar in both groups. RESULTS: In group A, 4 valves were replaced, 19 patients had mitral valve repair. In group B, 7 patients had valve replacement and 28 patients underwent mitral repair. Four patients in group A were converted to Chitwood technique due to endoclamp dysfunction. Operating time, CPB time, cross clamp time, and postoperative blood loss were lower in group B (operating time 295 +/- 83 min vs. 236 +/- 63.9 min; CPB min 167.6 = 64.9 min vs. 137.6 +/- 38.2 min; cross-clamp time 105.9 +/- 51.7 min vs. 78.9 +/- 25.2 min; postoperative blood loss 584 +/- 428 mL vs. 323 +/- 209 mL [p < 0.05]). Clinical outcome regarding postoperative mechanical ventilatilation time, hospital stay and hospital mortality was not different between groups. CONCLUSIONS: Minimally invasive mitral valve procedures via right anterolateral minithoracotomy, including complex valve repair, can be performed successfully using either technique. However, the Chitwood technique provides better intraoperative handling with shorter operation time and less postoperative blood loss. Additionally, costs of a procedure are less using the Chitwood technique compared to the Port-Access technique. PMID- 11204392 TI - The Leipzig experience with robotic valve surgery. AB - OBJECTIVES: The study describes the single-center experience using robot-assisted videoscopic mitral valve surgery and the early results with a remote telemanipulator-assisted approach for mitral valve repair. MATERIAL AND METHODS: Out of a series of 230 patients who underwent minimally invasive mitral valve surgery, in 167 patients surgery was performed with the use of robotic assistance. A voice-controlled robotic arm was used for videoscopic guidance in 152 cases. Most recently, a computer-enhanced telemanipulator was used in 15 patients to perform the operation remotely. RESULTS: The mitral valve was repaired in 117 and replaced in all other patients. The voice-controlled robotic arm (AESOP 3000) facilitated videoscopic-assisted mitral valve surgery. The procedure was completed without the need for an additional assistant as "solo surgery." Additional procedures like radiofrequency ablation and tricuspid valve repair were performed in 21 and 4 patients, respectively. Duration of bypass and clamp time was comparable to conventional procedures (107 A 34 and 50 A 16 min, respectively). Hospital mortality was 1.2%. Using the da Vinci telemanipulation system, remote mitral valve repair was successfully performed in 13 of 15 patients. CONCLUSION: Robotic-assisted less invasive mitral valve surgery has evolved to a reliable technique with reproducible results for primary operations and for reoperations. Robotic assistance has enabled a solo surgery approach. The combination with radiofrequency ablation (Mini Maze) in patients with chronic atrial fibrillation has proven to be beneficial. The use of telemanipulation systems for remote mitral valve surgery is promising, but a number of problems have to be solved before the introduction of a closed chest mitral valve procedure. PMID- 11204393 TI - Video assistance in minimal access mitral valve surgery. PMID- 11204394 TI - Generation of human bipedal locomotion by a bio-mimetic neuro-musculo-skeletal model. AB - To emulate the actual neuro-control mechanism of human bipedal locomotion, an anatomically and physiologically based neuro-musculo-skeletal model is developed. The human musculo-skeletal system is constructed as seven rigid links in a sagittal plane, with a total of nine principal muscles. The nervous system consists of an alpha motoneuron and proprioceptors such as a muscle spindle and a Golgi tendon organ for each muscle. At the motoneurons, feedback signals from the proprioceptors are integrated with the signal induced by foot-ground contact and input from the rhythm pattern generator; a muscle activation signal is produced accordingly. Weights of connection in the neural network are optimized using a genetic algorithm, thus maximizing walking distance and minimizing energy consumption. The generated walking pattern is in remarkably good agreement with that of actual human walking, indicating that the locomotory pattern could be generated automatically, according to the musculoskeletal structures and the connections of the peripheral nervous system, particularly due to the reciprocal innervation in the muscle spindles. Using the proposed model, the flow of sensory motor information during locomotion is estimated and a possible neuro-control mechanism is discussed. PMID- 11204395 TI - Competitive anatomical and physiological plasticity: a neurotrophic bridge. AB - Understanding the mechanisms of competitive synaptic plasticity, both anatomical and physiological, is of central importance to developmental neuroscience. Neurotrophic factors (NTFs) are implicated at almost every level of synaptic plasticity, from rapid physiological effects to slower anatomical effects, in addition to being implicated in competitive plasticity. Previously, we have built and analysed a mathematical model of anatomical synaptic plasticity based on competition for neurotrophic support. Here, we extend our work to build a combined, anatomical and physiological model. We find that, in order to understand the mechanisms of competitive physiological plasticity, we must postulate a central role for the change in expression of NTF receptors (NTFRs) on afferent synaptic terminals. Only by supposing that the expression of NTFRs is governed by NTF uptake do we find that physiological plasticity is competitive in character. We perform a fixed point analysis that establishes when afferent segregation is possible as a function of the parameters in the model, and simulate the model numerically to shed further light on its properties. A very clear prediction emerges from our model: that, as the efficacy of a terminal that is destined to be retracted due to competitive interactions reduces to zero, the NTFRs on that terminal should be down-regulated. Furthermore, our model requires that this reduction in synaptic efficacy never occurs significantly before the down-regulation in NTFRs. Such a prediction should be testable, and renders our model capable of being invalidated, in contrast to many other models of synaptic competition, which merely impose rather than seek to illuminate the quintessential feature of developmental synaptic plasticity. PMID- 11204396 TI - The economy of the shape of limbed animals. AB - A simple, high-level wire-minimization model appears to drive the relationship between animal limb number and body-to-limb proportion in some animals across at least seven phyla: annelids, arthropods, cnidarians, echinoderms, molluscs, tardigrades and vertebrates. Given an animal's body-to-limb proportion, the model enables one to estimate the animal's number of limbs, and vice versa. Informally, the model states that a limbed animal's large-scale morphology is set so as to maximize its number of limbs subject to the constraint that there is not a more economical shape which reaches out to the same places. A consequence of animals conforming to the model is that their large-scale morphology is "minimally wired." Just as wire minimization is important in artificial information processing devices, it is hypothesized that one reason why animals' large-scale morphologies conform to a save-wire principle is to minimize the system-wide information processing times. PMID- 11204397 TI - Estimating statistics of neuronal dynamics via Markov chains. AB - We present an efficient computational method for estimating the mean and variance of interspike intervals defined by the timing of spikes in typical orbits of one dimensional neuronal maps. This is equivalent to finding the mean and variance of return times of orbits to particular regions of phase space. Rather than computing estimates directly from time series, the system is modelled as a finite state Markov chain to extract stationary behaviour in the form of invariant measures and average absorption times. Ergodic-theoretic formulae are then applied to produce the estimates without the need to generate orbits directly. The approach may be applied to both deterministic and randomly forced systems. PMID- 11204398 TI - Combined Hebbian development of geniculocortical and lateral connectivity in a model of primary visual cortex. AB - We present a network model of visual map development in layer 4 of primary visual cortex. Our model comprises excitatory and inhibitory spiking neurons. The input to the network consists of correlated spike trains to mimick the activity of neurons in the lateral geniculate nucleus (LGN). An activity-driven Hebbian learning mechanism governs the development of both the network's lateral connectivity and feedforward projections from LGN to cortex. Plasticity of inhibitory synapses has been included into the model so as to control overall cortical activity. Even without feedforward input, Hebbian modification of the excitatory lateral connections can lead to the development of an intracortical orientation map. We have found that such an intracortical map can guide the development of feedforward connections from LGN to cortical simple cells so that the structure of the final feedforward orientation map is predetermined by the intracortical map. In a scenario in which left- and right-eye geniculocortical inputs develop sequentially one after the other, the resulting maps are therefore very similar, provided the intracortical connectivity remains unaltered. This may explain the outcome of so-called reverse lid-suture experiments, where animals are reared so that both eyes never receive input at the same time, but the orientation maps measured separately for the two eyes are nevertheless nearly identical. PMID- 11204399 TI - Silicon synaptic depression. AB - The recent quantitative description of activity-dependent depression in the synaptic transmission between cortical neurons has lead to many interesting suggestions of possible computational implications. Based on a simple biological model, we have constructed an analog circuit that emulates the properties of short-term depressing synapses. The circuit comprises only seven transistors and two capacitors per synapse, and is able to reproduce computational features of depressing synapses such as the 1/F law, the detection of long intervals of presynaptic silence and the sensitivity to redistribution of presynaptic firing rates. It provides a useful basis for implementing neural networks with dynamical synapses. PMID- 11204400 TI - Detection of simple radially symmetric targets: further evidence for the matched filter processing scheme in human pattern detection. AB - The detection of small radially symmetric targets was studied using a subthreshold summation paradigm. Small disc and disc-like patterns with diameters up to 0.60 were used for superposition on Bessel functions of zero order, subthreshold contrast and various spatial frequencies. Contrast interrelation functions prove linear over the whole range of contrasts used for the Bessel functions while their slopes show systematic variation with spatial frequency. An extrapolation of sensitivity from the slopes reveals that sensitivity can be predicted by a simple model assuming detection to be mediated by a transfer function made up as a cascade of an even bandpass function and the disc pattern spectrum, as has been found previously using one dimensional luminance distributions. Problems concerning the formation of pattern-specific radial symmetric filters are discussed. PMID- 11204401 TI - Topology selection by chaotic neurons of a pyloric central pattern generator. AB - The pyloric Central Pattern Generator (CPG) in the lobster has an architecture in which every neuron receives at least one connection from another member of the CPG. We call this a "non-open" network topology. An "open" topology, where at least one neuron does not receive synapses from any other CPG member, is found neither in the pyloric nor in the gastric mill CPG. Here we investigate a possible reason for this topological structure using the ability to perform a biologically functional task as a measure of the efficacy of the network. When the CPG is composed of model neurons that exhibit regular membrane voltage oscillations, open topologies are as able to maximize this functionality as non open topologies. When we replace these models by neurons which exhibit chaotic membrane voltage oscillations, the functional criterion selects non-open topologies. As isolated neurons from invertebrate CPGs are known in some cases to undergo chaotic oscillations, this suggests that there is a biological basis for the class of non-open network topologies that we observe. PMID- 11204402 TI - Interaction of the body, head, and eyes during walking and turning. AB - Body, head, and eye movements were measured in five subjects during straight walking and while turning corners. The purpose was to determine how well the head and eyes followed the linear trajectory of the body in space and whether head orientation followed changes in the gravito-inertial acceleration vector (GIA). Head and body movements were measured with a video-based motion analysis system and horizontal, vertical, and torsional eye movements with video-oculography. During straight walking, there was lateral body motion at the stride frequency, which was at half the frequency of stepping. The GIA oscillated about the direction of heading, according to the acceleration and deceleration associated with heel strike and toe flexion, and the body yawed in concert with stepping. Despite the linear and rotatory motions of the head and body, the head pointed along the forward motion of the body during straight walking. The head pitch/roll component appeared to compensate for vertical and horizontal acceleration of the head rather than orienting to the tilt of the GIA or anticipating it. When turning corners, subjects walked on a 50-cm radius over two steps or on a 200-cm radius in five to seven steps. Maximum centripetal accelerations in sharp turns were ca.0.4 g, which tilted the GIA ca.21 degrees with regard to the heading. This was anticipated by a roll tilt of the head of up to 8 degrees. The eyes rolled 1-1.5 degrees and moved down into the direction of linear acceleration during the tilts of the GIA. Yaw head deviations moved smoothly through the turn, anticipating the shift in lateral body trajectory by as much as 25 degrees. The trunk did not anticipate the change in trajectory. Thus, in contrast to straight walking, the tilt axes of the head and the GIA tended to align during turns. Gaze was stable in space during the slow phases and jumped forward in saccades along the trajectory, leading it by larger angles when the angular velocity of turning was greater. The anticipatory roll head movements during turning are likely to be utilized to overcome inertial forces that would destabilize balance during turning. The data show that compensatory eye, head, and body movements stabilize gaze during straight walking, while orienting mechanisms direct the eyes, head, and body to tilts of the GIA in space during turning. PMID- 11204404 TI - Neurons with large bilateral receptive fields in monkey prelunate gyrus. AB - In single-cell recordings from the dorsocaudal part of the prelunate gyrus of an alert monkey (Macaca fascicularis) we found neurons with unexpectedly large receptive fields (RFs) that spread bilaterally into the contra- and ipsilateral visual fields. These neurons (n=82) appeared to be clustered in the periphery of V4. They were surrounded by neurons with relatively small (3-10 degrees) and unilateral RFs in the contralateral field with properties similar to those previously described for neurons in area V4. Bilateral RFs extended over large parts of the lower visual field but always spared the fovea. Receptive fields typically revealed two foci of maximal responsiveness that were arranged symmetrically in the ipsi- and contralateral fields. Twenty-six cells did not respond to stimuli along the vertical meridian; these neurons had two distinct RFs. The preference for stimulus orientation, color, or motion was similar in all parts of these large RFs. PMID- 11204403 TI - Distribution of the neurotrophin receptors p75 and trkB in peripheral mechanoreceptors; observations on changes after injury. AB - The neurotrophin family mediates effects of growth, cell differentiation and cell death through low- and high-affinity transmembrane receptors. The Pacinian corpuscle (PC) is the largest peripheral mechanoreceptor in mammals and was studied by immuno-histochemistry and immuno-electron microscopy with regard to the distribution of neurotrophin receptors, p75; p140 trkA, p145 trkB and 145 trkC. TrkA- and trkC-like immunoreactivity (IR) was not expressed in rat and cat PCs. Developing and adult animals expressed p75 and trkB in lamellar cells of the PC. The inner core cells, thought to be specialised Schwann cells, demonstrated an injury-induced increased immuno-labelling for trk B. Perineurial-derived outer core cells were reactive to p75 after injury similar to the perineurium of distal nerve stumps. Inner core cells of PCs behaved as leptomeningeal cells with regard to trkB. Outer core lamellar cells of PCs behaved as perineurial cells with regard to p75. A role for brain-derived neurotrophic factor is proposed in the development and nerve regeneration of PCs via an anterograde messenger transfer through p75 and trkB. PMID- 11204405 TI - Conditioning of heteronymous H reflex in human temporalis muscle by stimulation of perioral afferents. AB - A heteronymous H reflex in the temporalis muscle can be elicited by selective stimulation of the masseteric nerve. The present study aimed at defining the optimal amplitude of the H reflex to detect inhibitory changes induced by stimulation of the perioral afferents and at providing new information on the control of masticatory muscles. Sixteen healthy volunteers participated in the experiment. A conditioning stimulus (CS) to the perioral skin was applied at various delays before an ipsilateral selective masseteric nerve stimulation (test stimulus: TS) while the subject was clenching the teeth at 25% of the maximal voluntary contraction. Two intensities of CS and TS were employed, high and low. The peak-to-peak amplitude of the H reflex (TS) and the root-mean-square value of the preceding electromyography were measured and the data analyzed by three-way analysis of variance and Tukey's posthoc tests. For both intensities used the heteronymous H reflex in the temporalis muscle was significantly decreased by prior activation of perioral afferents for delays from 5 to 60 ms. With a delay of 5 and 35 ms the preceding EMG level was not changed, while it was reduced at 20 and 60 ms delay. The intensities used to elicit the heteronymous H reflex of the temporalis muscle were appropriate to detect a reduction in motoneuron excitability. The reduction in the H reflex without a change in the preceding EMG at 5 and 35 ms delays could be due to presynaptic inhibition of the masseteric afferents exerted by the ipsilateral perioral afferents. PMID- 11204406 TI - Orientation of the opposition axis in mentally simulated grasping. AB - Five normal subjects were tested in a simulated grasping task. A cylindrical container filled with water was placed on the center of a horizontal monitor screen. Subjects used a precision grip formed by the thumb and index finger of their right hand. After a preliminary run during which the container was present, it was replaced by an image of the upper surface of the cylinder appearing on the horizontal computer screen on which the real cylinder was placed during the preliminary run. In each trial the image was marked with two contact points which defined an opposition axis in various orientations with respect to the frontal plane. The subjects' task consisted, once shown a stimulus, of judging as quickly as possible whether the previously experienced action of grasping the container full of water and pouring the water out would be easy, difficult or impossible with the fingers placed according to the opposition axis indicated on the circle. Response times were found to be longer for the grasps judged to be more difficult due to the orientation and position of the opposition axis. In a control experiment, three subjects actually performed the grasps with different orientations and positions of the opposition axis. The effects of these parameters on response time followed the same trends as during simulated movements. This result shows that simulated hand movements take into account the same biomechanical limitations as actually performed movements. PMID- 11204407 TI - Spatial- and verbal-memory improvement by cold-water caloric stimulation in healthy subjects. AB - We investigated the effects of unilateral cold-water vestibular stimulation on healthy subjects' performance in two cognitive tasks known to be differentially mediated by the two cerebral hemispheres. In a first experiment (right-hemisphere task), subjects memorized object-location associations while being stimulated with cold water in the left ear or right ear or not at all (control group). In the second experiment (left-hemisphere task), subjects memorized a list of sequentially presented function words while being stimulated in the same manner as the subjects in the first experiment. A recall phase followed each encoding phase. In the first experiment, subjects who had been stimulated in the left ear recalled the object locations significantly faster than subjects who had been stimulated in the right ear and those in the control group. The second experiment yielded the reverse pattern: correct word recognition was faster for subjects who had been stimulated in the right ear than for subjects stimulated in the left ear and those of the control group. We suggest that unilateral caloric stimulation leads to a selective activation of contralateral cerebral structures and speeds up cognitive processes mediated by these structures. These results are discussed with respect to findings in neglect patients and functional-imaging studies in healthy subjects. PMID- 11204408 TI - Somatosensory attunement to the rigid body laws. AB - In the most general case, haptic perception of an object's heaviness is most likely the perception of the object's resistance to movement, determined jointly by the object's mass and mass distribution. In two experiments with occluded objects wielded freely in three dimensions, we showed additive effects on perceived heaviness of mass and the inertia tensor. Our manipulations of the inertia tensor were directed specifically at the volume and symmetry of the inertia ellipsoid, quantities that can be understood as important to controlling the level and patterning of muscular forces, respectively. Ellipsoid volume and symmetry were found to have separate effects on perceptual reports of heaviness that were invariant over different tensors. Independent sensitivities to translational inertia and particular characterizations of rotational inertia suggest specialized somatosensory attunement to the rigid body laws. PMID- 11204409 TI - The visual-oculomotor striatum of the cat: functional relationship to the superior colliculus. AB - The visual-recipient sector of the cat striatum receives corticostriate input from over 15 higher visual and oculomotor-related areas of the cortex and appears homologous with the physiologically characterized region of mixed visual and oculomotor inputs within the primate caudate nucleus. This area in the cat involves the dorsolateral caudate and a strip of the caudal putamen. In a first series of experiments, the former was injected with a retrograde tracer in several cats. Thalamostriate cells were found in extensive regions, including the intralaminar nuclei, certain motor-related nuclei, and, most notably, across much of the extrageniculate visual thalamus. In another set of experiments, anterograde tracers were also injected into the superior colliculus (SC), and labeled tectothalamic fibers were observed in all thalamic sites projecting to the visual-recipient striatum. These findings highlight for the first time the need for the SC to be considered in models of thalamostriate and visual/oculomotor-striatal function(s). Moreover, the data bring to light the fact that basal-ganglia outflow reaching the SC via striatonigro-nigrotectal circuitry is well positioned to modulate ascending tecto-thalamic-thalamostriatal signals destined for the visual-recipient striatum. PMID- 11204410 TI - Generalized induction of 72-kDa heat-shock protein after transient focal ischemia in rat brain. AB - The time course of 72-kDa heat-shock protein (hsp72) induction was evaluated by immunoblotting in cerebral cortex, striatum, hippocampus, cerebellum, liver, and kidney of rats subjected to 60-min focal cerebral ischemia following proximal unilateral occlusion of the right middle cerebral artery (MCA). Neurological examinations indicated that maximum deficits in reflex and sensorimotor functions occurred 24-48 h after reperfusion (40% lower than baseline), while significant recovery occurred at 72 h (33% higher than 48 h). hsp72 was present in all tissues at 6 h. The regions perfused by the occluded MCA showed a higher induction than the corresponding contralateral ones. hsp72 reached its maximum level in ipsilateral cerebral cortex and striatum at 24 h, whereas in the contralateral cortex and cerebellum the protein reached its maximum expression at 48 h, that is 24 h before functional recovery. This delay suggests a role of the protein in plastic events sustaining neurological recovery. PMID- 11204411 TI - Metabotropic glutamate receptors modify ionotropic glutamate responses in neocortical pyramidal cells and interneurons. AB - In neocortex glutamate activates ionotropic and metabotropic receptors (mGluRs). Whole-cell current-clamp recordings in the in vitro rat auditory cortex at 32 degrees C were used to explore the role that mGluRs have in regulation of AMPA/kainate, NMDA, and GABA receptor-mediated synaptic transmission. Our findings are: (a) The fast EPSP (AMPA/kainate), slow EPSP (NMDA), and IPSPs (GABAA, GABAB), elicited in pyramidal neurons are reduced in the presence of (1S,3R)-ACPD (mGluR agonist) with greatest effect on the slow IPSP>fast IPSP>>fast EPSP. The effect is likely the result of ACPD acting at presynaptic mGluRs because the probability of release of glutamate and GABA is reduced in the presence of ACPD, intracellular infusion of a G protein antagonist (GDPPS) did not block the effect of ACPD, nor were iontophoretic kainic acid or NMDA-induced depolarizations reduced by ACPD. (b) The slow EPSP is enhanced following washout of ACPD and enhancement is not due to disinhibition because it is present in the absence of IPSPs, but if IPSPs are present, its magnitude can be influenced. Iontophoretic NMDA responses are enhanced in the presence of ACPD, an effect blocked by GDPbetaS and heparin (intracellular inositol 1,4,5-trisphosphate receptor antagonist). Taken together, this evidence suggests that enhancement is a result of group I postsynaptic mGluR activation. (c) In fast-spiking cells ACPD reduces the EPSP (AMPA/kainate and NMDA-mediated). This action is likely presynaptic because it persists when GDPbetaS is in the cells. (d) The rate of spike discharge recorded from fast-spiking cells is accelerated in ACPD but does not change in the presence of GDPbetaS, suggesting a postsynaptic effect. Our data indicate that mGluRs can influence neocortical synaptic transmission in complex ways by acting presynaptically and postsynaptically. PMID- 11204412 TI - Intermediate cerebellum and conditioned eyeblinks. Parallel involvement in eyeblinks and tonic eyelid closure. AB - The intermediate cerebellum (the intermediate cerebellar cortex and interposed nuclei) and associated brainstem circuits are essential for the acquisition and expression of classically conditioned eyeblinks in the rabbit. The purpose of the present experiment was to determine whether these circuits are also involved in adaptive eyelid closure learned in an instrumental paradigm. For that purpose, rabbits with unrestrained eyelids were trained in two tasks: (1) classical conditioning of the eyeblink; and (2) a new instrumental task in which they avoided delivery of an aversive stimulus by maintaining tonic eyelid closure. To examine the involvement of the intermediate cerebellum in these two types of learned behavior, the cerebellar interposed nuclei were injected with the GABAA agonist muscimol and with the GABAA antagonist picrotoxin. Inactivating the interposed nuclei with muscimol abolished classically conditioned eyeblinks and severely affected the rabbit's capacity to maintain tonic eyelid closure. On the other hand, reducing inhibition with picrotoxin failed to interrupt the learned responses and increased the amplitude of eyelid closure. These data indicate that the cerebellar interposed nuclei control both phasic classically conditioned eyeblinks and tonic instrumental eyelid closure. To account for this new finding, a "hybrid" hypothesis combining the cerebellar learning hypothesis and the performance hypothesis is proposed. PMID- 11204413 TI - Projections from ventrolateral hypothalamic neurons containing progesterone receptors and somatostatin to the midbrain central gray in the female guinea pig. AB - The goal of this study was to determine, by combining retrograde fluorescent tract tracing with double immunocytochemistry, whether neurons immunoreactive (IR) for both progesterone receptors (PR) and somatostatin (SOM) in the guinea pig ventrolateral nucleus (VL) send their axons directly to the midbrain. Unilateral microinjections of true blue (TB) fluorescent dye were made into the midbrain central gray (MCG) of ovariectomized animals primed with estradiol to induce PR and injected intracerebroventricularly with colchicine to visualize SOM IR neurons. The highest number of PR/SOM-IR neurons in the VL that projected to the midbrain was found when the fluorescent retrograde tracer was confined to the lateral region of the MCG at the mid-rostrocaudal level. More specifically, 29% of the progesterone target neurons containing SOM detected in the VL projected directly to the midbrain, accounting for 7% of the PR-IR neurons and for 9% of the SOM-IR neurons. These triple-labeled cells were found throughout the extent of the VL. Double-labeled cells also sent axons to the MCG and were either PR-IR (14%) or SOM-IR (12%). These results provide morphological evidence that a subset of the PR-IR neurons expressing SOM in the VL have long projections to the midbrain and suggest that the SOM system may modulate neural circuits involved in the regulation of steroid-influenced behaviors and neuroendocrine functions. PMID- 11204414 TI - Origins and violations of the 2/3 power law in rhythmic three-dimensional arm movements. AB - The 2/3 power law, the nonlinear relationship between tangential velocity and radius of curvature of the end-effector trajectory, is thought to be a fundamental constraint of the central nervous system in the formation of rhythmic endpoint trajectories. However, studies on the 2/3 power law have been confined largely to planar drawing patterns of relatively small size. With the hypothesis that this strategy overlooks nonlinear effects that are constitutive in movement generation, the present experiments tested the validity of the power law in elliptical patterns that were not confined to a planar surface and which were performed by the unconstrained 7-degrees of freedom (DOF) arm, with significant variations in pattern size and workspace orientation. Data were recorded from five human subjects where the seven joint angles and the endpoint trajectories were analyzed. Additionally, an anthropomorphic 7-DOF robot arm served as a "control subject" whose endpoint trajectories were generated on the basis of the human joint angle data, modeled as simple harmonic oscillations. Analyses of the endpoint trajectories demonstrate that the power law is systematically violated with increasing pattern size, in both exponent and the goodness of fit. The origins of these violations can be explained analytically based on smooth, rhythmic trajectory formation and the kinematic structure of the human arm. We conclude that, in unconstrained rhythmic movements, the power law seems to be a by-product of a movement system that favors smooth trajectories, and that it is unlikely to serve as a primary movement-generating principle. Our data rather suggest that subjects employed smooth oscillatory pattern generators in joint space to realize the required movement patterns. PMID- 11204415 TI - The ability to execute saccades on the basis of efference copy: impairments in double-step saccade performance in children with developmental co-ordination disorder. AB - The double-step saccade task (DSST) was used to test the hypothesis that children with developmental co-ordination disorder (DCD) who experience deficits in motor imagery have difficulty processing the visual spatial consequences of intended movements using efference copy signals. In order to ensure that the second saccade in the DSST was executed in the absence of visual cues and had to be programmed on the basis of extra-retinal information (efference copy), we analysed only those double-step ensembles where latency plus duration of first saccades was greater than 240 ms (total presentation time of the targets). No significant differences between DCD and control children were evident on measures of latency of first saccades, intersaccadic interval and first saccade error. As predicted, children with DCD who have impaired motor imagery demonstrated specific deficits on the DSST where efference copy had been used to program the saccade sequence. More specifically, these children were less accurate in terms of final eye position on second saccades. Our results raise the possibility that abnormalities in the processing of efference copy signals could underlie motor clumsiness in the majority of children with DCD. Furthermore, the origin of this deficit in efference copy probably exists at the level of the parietal lobe. PMID- 11204416 TI - Horizontal ocular vergence and the three-dimensional response to whole-body roll motion. AB - We evaluated the human binocular response to roll motion in the dark and during visual fixation with horizontal convergence. Six normal human subjects were exposed to manually driven, whole-body rotation about an earth-vertical, naso occipital axis, under two conditions: (I) oscillation at 0.4 Hz (peak velocity 69+/-3.8 degree/s) in the dark, and whilst fixating an axial light-emitting diode at 48 cm ('near') and at 206 cm ('far'); (II) constant velocity rotation (56.5+/ 3.1 degree/s) for 40 s, clockwise and counter-clockwise, in the dark, and sudden stops. Eye and head movements were monitored using scleral search coils. In head fixed, angular velocity coordinates roll motion always evoked conjugate ocular torsion, with small conjugate horizontal and disconjugate vertical components. The resultant binocular eye responses were rotations about convergent axes. During oscillation with target fixation the convergence of the rotation axes was larger than that predicted by target geometry, producing disconjugate oscillations of vertical gaze about the target ('skewing'). Fast-phase eye movements were primarily resetting rotations about the same convergent rotation axes as the slow phases, but the small vertical velocity components had oscillatory, asymmetrical profiles. In response to velocity steps the slow-phase eye velocity decayed exponentially with time constants of 4.5+/-1.5 s for the torsional component and 5.8+/-1.9 s for the 'vertical vergence' component (right eye-left eye recordings). We conclude that in normal human subjects dynamic vertical canal stimulation with horizontal gaze convergence evokes rotation of the eyes about convergent axes and a small skewing of the eyes. PMID- 11204417 TI - Chronic intracerebroventricular exposure to beta-amyloid(1-40) impairs object recognition but does not affect spontaneous locomotor activity or sensorimotor gating in the rat. AB - This study examined the cognitive effects of chronic in vivo exposure to beta amyloid(1-40) via the intracerebroventricular route on two distinct paradigms. The first test evaluated a form of early attentional control referred to as sensorimotor gating in which an antecedent weak prepulse stimulus modulates the reactivity to a subsequent startle-eliciting stimulus. The second test utilized the spontaneous preference for a novel object over that of a familiar one in rats as a measure of object recognition memory. We found that beta-amyloid exposure leads to a severe deficit in the object memory test but spares sensorimotor gating. Moreover, unlike the water maze deficit induced by beta-amyloid (Nag et al., in preparation), the deficit on object recognition was resistant to amelioration by systemic physostigmine treatment at a dose of 0.06 mg/kg per day intraperitoneally. The present results add to previous reports that beta-amyloid exposure can lead to deficits on hippocampal lesion sensitive tasks, suggesting that dysfunction of the rhinal cortices in addition to that of the septohippocampal system is implicated in beta-amyloid-induced behavioral impairments. It therefore lends support to the hypothesis that beta-amyloid exposure can lead to severe impairment across multiple memory systems. PMID- 11204418 TI - Good maintenance of exercise-induced bone gain with decreased training of female tennis and squash players: a prospective 5-year follow-up study of young and old starters and controls. AB - This prospective 5-year follow-up study of 64 adult female racquet sports players and 27 controls assessed the changes in the playing-to-nonplaying arm bone mineral content (BMC) differences to answer three questions: (1) Are training induced bone gains lost with decreased training? (2) Is the bone response to decreased training different if the playing career has been started before or at puberty rather than after it? (3) Are the possible bone changes related to the changes in training? The players were divided into two groups according to the starting age of their tennis or squash playing. The mean starting age was 10.5 years (SD, 2.2) among the players who had started training before or at menarche (young starters; n = 36) while 26.4 years (SD, 8.0) among those players who had begun training a minimum of 1 year after menarche (old starters; n = 28). At baseline of the 5-year follow-up, the mean age of the young starters was 21.6 years (SD, 7.6) and that of old starters was 39.4 years (SD, 10.5). During the follow-up, the young starters had reduced the average training frequency from 4.7 times a week (2.7) to 1.4 times a week (1.3) and the old starters from 4.0 times a week (1.4) to 2.0 times a week (1.4), respectively. The 5-year follow-up revealed that despite reduced training the exercise-induced bone gain was well maintained in both groups of players regardless of their clearly different starting age of activity and different amount of exercise-induced bone gain. The gain was still 1.3-2.2 times greater in favor of the young starters (at the follow-up, the dominant-to-nondominant arm BMC difference was 22% [8.4] in the humeral shaft of the young starters versus 10% [3.8] in the old starters, and 3.5% [2.4] in controls). In the players, changes in training were only weakly related to changes in the side-to-side BMC difference (r(s) = 0.05-0.34, all NS), and this was true even among the players who had stopped training completely a minimum 1 year before the follow-up. In conclusion, if controlled interventions will confirm our findings that an exercise-induced bone gain can be well maintained with decreased activity and that the maintenance of the bone gain is independent of the starting age of activity, exercise can be recommended for preventing osteoporosis and related fractures. PMID- 11204419 TI - Exercise maintains bone mass, but do people maintain exercise? PMID- 11204420 TI - Variation in bone biomechanical properties, microstructure, and density in BXH recombinant inbred mice. AB - To test the hypothesis that factors associated with bone strength (i.e., volumetric bone mineral density [vBMD], geometry, and microstructure) have heritable components, we exploited the 12 BXH recombinant inbred (RI) strains of mice derived from C57BL/6J (B6; low bone mass) and C3H/HeJ (C3H; high bone mass) progenitor strains. The femurs and lumbar vertebrae from each BXH RI strain were characterized for phenotypes of vBMD, microstructural, biomechanical, and geometrical properties. Methods included bending (femur) and compression (vertebra) testing, peripheral quantitative computed tomography (pQCT), and microcomputed tomography (microCT). Segregation patterns of femoral and vertebral biomechanical properties among the BXH RI strains suggested polygenic regulation. Femoral biomechanical properties were strongly associated with femoral width in the anteroposterior (AP) direction and cortical thickness--geometric properties with complex genetic regulation. Vertebral vBMD and biomechanical properties measured in BXH RI strains showed a greater variability than either B6 or C3H progenitors, suggesting both progenitor strains have independent subsets of genes that yield similar vBMD and strength. The microCT and pQCT data suggested that the distribution of vertebral mineral into cortical and trabecular compartments is regulated genetically. Although the B6 and C3H progenitors had similar vertebral strength, their vertebral structures were markedly different: B6 had good trabecular bone structure and modest cortical bone mineral content (BMC), whereas C3H had high cortical BMC combined with a deficiency in trabecular structure. These structural traits segregated independently in the BXH RI strains. Finally, vertebral strength was not correlated consistently with femoral strength among the BXH RI strains, suggesting genetic regulation of bone strength is site specific. PMID- 11204421 TI - Localization of estrogen receptor beta protein expression in adult human bone. AB - Evidence suggests that the newly described estrogen receptor beta (ER-beta) may be important for estrogen (17beta-estradiol) action on the skeleton, but its cellular localization in adult human bone requires clarification. We addressed this by using indirect immunoperoxidase with a novel affinity purified polyclonal antibody to human ER-beta, raised to hinge domain (D) sequences from the human receptor. Bone was demineralized in 20% EDTA and all biopsy specimens were formalin-fixed and wax-embedded. Vigorous retrieval was essential for ER-beta detection. In sections (5 microm) of benign prostate hyperplasia, used as positive control, clear nuclear immunoreactivity was seen in glandular epithelial cells, with a 1:500 dilution of ER-beta40. For bone sections, optimal antibody dilutions were 1:100-1:250. We found that in normal bone (from graft operations), in fracture callus from both men and women (>25 years old), pagetic bone, osteophytes, and secondary hyperparathyroid bone, all from older patients, ER beta was expressed clearly in osteoclast nuclei, with little cytoplasmic immunoreactivity. Nuclear immunoreactivity was still prominent in osteoclasts, with antibody diluted 1:500, although it faded in other cells. Osteoblasts, in areas of active bone formation or bone remodeling, also expressed ER-beta, as did some osteocytes. However, hypertrophic chondrocytes were negative, unlike mesenchymal cells, adjacent to the osteogenesis. Megakaryocytes and some capillary blood vessels cells were receptor positive. All ER-beta expression was blocked totally by preincubation of antibody with antigen. We conclude that ER beta is expressed in cells of osteoblast lineage and in osteoclasts. The latter appear relatively abundant in this receptor and this might provide a means for direct action of estrogen on osteoclasts. PMID- 11204422 TI - Transcriptional induction of matrix metalloproteinase-13 (collagenase-3) by 1alpha,25-dihydroxyvitamin D3 in mouse osteoblastic MC3T3-E1 cells. AB - The removal of unmineralized matrix from the bone surface is essential for the initiation of osteoclastic bone resorption because osteoclasts cannot attach to the unmineralized osteoid. Matrix metalloproteinases (MMPs) are known to digest bone matrix. We recently reported that among the MMPs expressed in mouse osteoblastic cells, MMP-13 (collagenase-3) was the one most predominantly up regulated by bone resorbing factors including 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3]. In this study, we examined the mechanism of regulation of MMP 13 expression by 1alpha,25(OH)2D3 in mouse osteoblastic MC3T3-E1 cells. 1Alpha,25(OH)2D3 increased steady-state messenger RNA (mRNA) and protein levels of MMP-13. De novo protein synthesis was essential for the induction because cycloheximide (CHX) decreased the effect of 1alpha,25(OH)2D3 on the MMP-13 mRNA level. 1Alpha,25(OH)2D3 did not alter the decay of MMP-13 mRNA in transcriptionally arrested MC3T3-E1 cells; however, it increased the MMP-13 heterogeneous nuclear RNA (hnRNA) level and MMP-13 transcriptional rate. The binding activity of nuclear extracts to the AP-1 binding site, but not to the Cbfa1 binding site, in the MMP-13 promoter region was up-regulated by 1alpha,25(OH)2D3, suggesting the mediation of AP-1 in this transcriptional induction. To determine the contribution of MMPs to bone resorption by 1alpha,25(OH)2D3, the inhibitory effect of BB94, an MMP inhibitor, on resorbed pit formation by mouse crude osteoclastic cells was examined on either an uncoated or collagen-coated dentine slice. BB94 did not prevent resorbed pit formation on uncoated dentine whereas it did on collagen-coated dentine. We therefore propose that the transcriptional induction of MMP-13 in osteoblastic cells may contribute to the degradation of unmineralized matrix on the bone surface as an early step of bone resorption by 1alpha,25(OH)2D3. PMID- 11204423 TI - Bioactive glass stimulates in vitro osteoblast differentiation and creates a favorable template for bone tissue formation. AB - In this study, we have investigated the behavior of fetal rat osteoblasts cultured on bioactive glasses with 55 wt% silica content (55S) and on a bioinert glass (60S) used either in the form of granules or in the form of disks. In the presence of Bioglass granules (55 wt% silica content), phase contrast microscopy permitted step-by-step visualization of the formation of bone nodules in contact with the particles. Ultrastructural observations of undecalcified sections revealed the presence of an electron-dense layer composed of needle-shaped crystals at the periphery of the material that seemed to act as a nucleating surface for biological crystals. Furthermore, energy dispersive X-ray (EDX) analysis and electron diffraction patterns showed that this interface contains calcium (Ca) and phosphorus (P) and was highly crystalline. When rat bone cells were cultured on 55S disks, scanning electron microscopic (SEM) observations revealed that cells attached, spread to all substrata, and formed multilayered nodular structures by day 10 in culture. Furthermore, cytoenzymatic localization of alkaline phosphatase (ALP) and immunolabeling with bone sialoprotein antibody revealed a positive staining for the bone nodules formed in cultures on 55S. In addition, the specific activity of ALP determined biochemically was significantly higher in 55S cultures than in the controls. SEM observations of the material surfaces after scraping off the cell layers showed that mineralized bone nodules remained attached on 55S surfaces but not on 60S. X-ray microanalysis indicated the presence of Ca and P in this bone tissue. The 55S/bone interfaces also were analyzed on transverse sections. The interfacial analysis showed a firm bone bonding to the 55S surface through an intervening apatite layer, confirmed by the X-ray mappings. All these results indicate the importance of the surface composition in supporting differentiation of osteogenic cells and the subsequent apposition of bone matrix allowing a strong bond of the bioactive materials to bone. PMID- 11204424 TI - Parathyroid hormone enhances fluid shear-induced [Ca2+]i signaling in osteoblastic cells through activation of mechanosensitive and voltage-sensitive Ca2+ channels. AB - Osteoblasts respond to both fluid shear and parathyroid hormone (PTH) with a rapid increase in intracellular calcium concentration ([Ca2+]i). Because both stimuli modulate the kinetics of the mechanosensitive cation channel (MSCC), we postulated PTH would enhance the [Ca2+]i response to fluid shear by increasing the sensitivity of MSCCs. After a 3-minute preflow at 1 dyne/cm2, MC3T3-E1 cells were subjected to various levels of shear and changes in [Ca2+]i were assessed using Fura-2. Pretreatment with 50 nM bovine PTH(1-34) [bPTH(1-34)] significantly enhanced the shear magnitude-dependent increase in [Ca2+]i. Gadolinium (Gd3+), an MSCC blocker, significantly inhibited the mean peak [Ca2+]i response to shear and shear + bPTH(1-34). Nifedipine (Nif), an L-type voltage-sensitive Ca2+ channel (VSCC) blocker, also significantly reduced the [Ca2+]i response to shear + bPTH(1 34), but not to shear alone, suggesting VSCC activation plays an interactive role in the action of these stimuli together. Activation of either the protein kinase C (PKC) or protein kinase A (PKA) pathways with specific agonists indicated that PKC activation did not alter the Ca2+ response to shear, whereas PKA activation significantly increased the [Ca2+]i response to lower magnitudes of shear. bPTH(1 34), which activates both pathways, induced the greatest [Ca2+]i response at each level of shear, suggesting an interaction of these pathways in this response. These data indicate that PTH significantly enhances the [Ca2+]i response to shear primarily via PKA modulation of the MSCC and VSCC. PMID- 11204425 TI - Expression of functional gap junctions and regulation by fluid flow in osteocyte like MLO-Y4 cells. AB - Osteocytes are thought to be mechanosensory cells that respond to mechanical stress by sending signals to other bone cells to initiate bone remodeling. An osteocyte-like cell line MLO-Y4 provides a model system to examine whether gap junctions participate in the regulation of osteocyte function and signaling by mechanical stress. In this study, we show that MLO-Y4 cells are coupled and that gap junction channels mediate this coupling. Biochemical analyses show that connexin 43 (Cx43) is a major gap junction protein expressed in MLO-Y4 cells and approximately 5% of Cx43 protein is phosphorylated. MLO-Y4 cells were exposed to mechanical stress using a parallel plate flow chamber to model bone fluid flow shear stress. Fluid flow increased significantly the length of the dendritic processes, a morphological characteristic of osteocytes. A redistribution of the gap junction protein, Cx43 also was observed from a location circling the nucleus to punctate spots in the cytoplasm and in the dendritic processes. "Scrape loading" dye transfer analyses showed that fluid flow increased intercellular coupling and increased the number of cells coupled immediately after fluid flow treatment, in direct proportion to shear stress magnitude. Although intercellular coupling continued to increase, stimulation of Cx43 protein expression during the poststress period was found to be biphasic. Cx43 protein was elevated 30 minutes after application of stress but decreased at 24 h poststress. Pulsating fluid flow had a similar stimulatory effect as steady fluid flow on gap junctions. However, this stimulatory effect in osteocyte-like cells was not observed in osteoblast-like 2T3 cells. Together, these results show that fluid flow has stimulatory effects on osteocyte-like MLO-Y4 cells with early effects on cellular morphology, opening of gap junctions, and redistribution of Cx43 protein and delayed effects on Cx43 protein expression. The high expression of Cx43 and its location in the cytoplasm also suggest that Cx43 may have unknown functions in addition to forming gap junctions. These studies indicate that gap junctions may serve as channels for signals generated by osteocytes in response to mechanical loading. PMID- 11204426 TI - The transition of cadherin expression in osteoblast differentiation from mesenchymal cells: consistent expression of cadherin-11 in osteoblast lineage. AB - Osteoblasts are derived originally from pluripotent mesenchymal stem cells on migration into the bone matrix. To elucidate the contribution of classical cadherins in this differentiation pathway, we developed a new protocol for their analysis and studied their specific expressions in various cell lines of the mesenchymal lineage, including osteoblasts. N-cadherin was expressed constitutively in all cell lines examined except an osteocyte-like cell line whereas cadherin-11 was expressed selectively in preosteoblast and preadipocyte cell lines. P-cadherin also was expressed in primary cultures of calvarial cells and mature osteoblasts at a relatively low level compared with N-cadherin and cadherin-11. M-cadherin was expressed only in a premyoblast cell line. We observed the transition of cadherin expression from M-cadherin to cadherin-11 in the premyoblast cell line when osteogenic differentiation was induced by treatment with bone morphogenetic protein 2 (BMP-2), while the expression of N cadherin remained unchanged. In contrast, when a preadipocyte cell line, which shows a similar pattern of cadherin expression to osteoblasts, was induced to undergo adipogenic differentiation, the expression of N-cadherin and cadherin-11 was decreased. These observations characterize the cadherin expression profile of mesenchymal lineage cells, especially osteoblasts, which regularly express cadherin-11. Cadherin-11 may affect cell sorting, alignment, and separation through differentiation. PMID- 11204427 TI - The dose-response effects of ethanol on the human fetal osteoblastic cell line. AB - Alcohol is a risk factor for the development of osteoporosis, especially in men. Chronic alcohol abuse decreases bone mass, which contributes to the increased incidence of fractures. To better understand the mechanism of action of ethanol on bone metabolism, we have studied the dose-response effects of ethanol on conditionally immortalized human fetal osteoblasts (hFOB) in culture. Ethanol treatment had no significant effects on osteoblast number after 1 day or 7 days. Ethanol treatment did not reduce type I collagen protein levels at either time point at any dose but slightly reduced alkaline phosphatase activity after 7 days. The messenger RNA (mRNA) levels for alkaline phosphatase, type I collagen, and osteonectin were unaltered by 24 h of ethanol treatment but a high dose (200 mM) reduced mRNA levels for the two bone matrix proteins after 7 days. Ethanol treatment led to dose-dependent increases in transforming growth factor beta1 (TGF-beta1) mRNA levels and decreases in TGF-beta2 mRNA levels. The concentration of ethanol in the medium decreased with time because of evaporation but there was little degradation caused by metabolism. These results, which show that cultured osteoblasts are less sensitive than osteoblasts in vivo, suggest that the pronounced inhibitory effects of ethanol on bone formation are not caused by direct cell toxicity. PMID- 11204428 TI - Bone mineralization and osteoblast differentiation are negatively modulated by integrin alpha(v)beta3. AB - Numerous bone matrix proteins can interact with alpha(v)-containing integrins including alpha(v)beta3. To elucidate the net effects of the interaction between these proteins and alpha(v)beta3 on osteoblast function, we developed a murine osteoblastic cell line that overexpressed human alpha(v)beta3. Human alpha(v)beta3-integrin was expressed on cell membrane, in which its presence did not alter the surface level of endogenous mouse alpha(v)beta3. The expressed human alpha(v)beta3 was functional because cell adhesion to osteopontin was increased and this increment was abolished by antibody against human alpha(v)beta3. The proliferation rate of cells overexpressing alpha(v)beta3 (alpha(v)beta3-cells) was increased whereas matrix mineralization was decreased. To elucidate the mechanisms leading to inhibition of matrix mineralization, the expression of proteins important for mineralization was analyzed. Alkaline phosphatase activity and the expression of osteocalcin, type I collagen, and bone sialoprotein (BSP) were decreased whereas osteopontin was stimulated in alpha(v)beta3-cells. The regulation of osteopontin, osteocalcin, and BSP expression was mediated via transcriptional mechanism because their promoter activities were altered. Examination of molecules involved in integrin signaling indicated that activator protein-1 (AP-1) and extracellular signal-regulated kinase (Erk) activities were enhanced whereas c-jun N-terminal kinase (JNK) activity was decreased in alpha(v)beta3-cells. The activity of p38 and the levels of focal adhesion kinase (FAK) and vinculin were not altered. Moreover, the adhesions of alpha(v)beta3-cells to type I collagen and fibronectin were inhibited, which was attributed to decreased beta1-integrin levels on cell surface. In conclusion, overexpressing alpha(v)beta3-integrin in osteoblasts stimulated cell proliferation but retarded differentiation, which were derived via altered integrin-matrix interactions, signal transduction, and matrix protein expression. PMID- 11204429 TI - Localizational alterations of calcium, phosphorus, and calcification-related organics such as proteoglycans and alkaline phosphatase during bone calcification. AB - To further approach the mechanisms of bone calcification, embryonic rat calvariae were observed at electron microscopic level by the means of fine structures and various cytochemical localizations, including nonspecific proteoglycan (PG) stained by cuprolinic blue (CB), decorin, chondroitin sulfate, hyaluronan, and alkaline phosphatase (ALP), as well as the elemental mapping of calcium (Ca) and phosphorus (P) by energy-filtering transmission electron microscopy (EFTEM). In the calvariae, calcification advanced as the distance from osteoblasts increased. Closer to the osteoblasts, the osteoid was marked by an abundance of CB-positive PGs around collagen fibrils. After crystallization within matrix vesicles, calcified nodules formed and expanded, creating a coherent calcified matrix. The sizes of CB-positive PG-like structures diminished as calcification proceeded. Although small CB-positive structures were accumulated in early stage-calcified nodules, they were localized along the periphery of larger calcified nodules. Cytochemical tests for decorin, chondroitin sulfate, and hyaluronan determined their presence in the areas around collagen fibrils of the osteoid, as well as in and around calcified nodules, whereas ALP was found in the matrix vesicles, as well as in and around the calcified nodules. Ca tended to localize at the PG sites, while P often mapped to the collagen fibril structures, in the uncalcified matrix. In contrast, Ca/P colocalization was visible in and around the calcified nodules, where ALP and smaller CB-positive structures were observed. The difference in the localization patterns of Ca and P in uncalcified areas may limit the local [Ca2+][PO4(3-)] product, leading to the general inhibition of hydroxyapatite crystallization. The downsizing of CB-positive structures suggested enzymatic fragmentation of PGs. Such structural alterations would contribute to the preservation and transport of calcium. ALP possesses the ability to boost local phosphate anion concentration. Therefore, structurally altered PGs and ALP may cooperate in Ca/P colocalization, thus promoting bone calcification. PMID- 11204431 TI - A novel cell culture model of chondrocyte differentiation during mammalian endochondral ossification. AB - Endochondral ossification (EO) occurs in the growth plate where chondrocytes pass through discrete stages of proliferation, maturation, hypertrophy, and calcification. We have developed and characterized a novel bovine cell culture model of EO that mirrors these events and will facilitate in vitro studies on factors controlling chondrocyte differentiation. Chondrocytes derived from the epiphyses of long bones of fetal calves were treated with 5-azacytidine (aza-C) for 48 h. Cultures were maintained subsequently without aza-C and harvested at selected time points for analyses of growth and differentiation status. A chondrocytic phenotype associated with an extensive extracellular matrix rich in proteoglycans and collagen types II and VI was observed in aza-C-treated and untreated cultures. aza-C-treated cultures were characterized by studying the expression of several markers of chondrocyte differentiation. Parathyroid hormone related protein (PTHrP) and its receptor, both markers of maturation, were expressed at days 5-9. Type X collagen, which is restricted to the stage of hypertrophy, was expressed from day 11 onward. Hypertrophy was confirmed by a 14 fold increase in cell size by day 15 and an increased synthesis of alkaline phosphatase during the hypertrophic period (days 14-28). The addition of PTHrP to aza-C-treated cultures at day 14 led to the down-regulation of type X collagen by 6-fold, showing type X collagen expression is under the control of PTHrP as in vivo. These findings show that aza-C can induce fetal bovine epiphyseal chondrocytes to differentiate in culture in a manner consistent with that which occurs during the EO process in vivo. PMID- 11204430 TI - Strontium ranelate increases cartilage matrix formation. AB - Based on previous studies showing that strontium ranelate (S12911) modulates bone loss in osteoporosis, it could be hypothesized that this drug also is effective on cartilage degradation in osteoarthritis (OA). This was investigated in vitro on normal and OA human chondrocytes treated or not treated with interleukin-1beta (IL-1beta). This model mimics, in vitro, the imbalance between chondroformation and chondroresorption processes observed in vivo in OA cartilage. Chondrocytes were isolated from cartilage by enzymatic digestion and cultured for 24-72 h with 10(-4)-10(-3) M strontium ranelate, 10(-3) M calcium ranelate, or 2 x 10(-3) M SrCl2 with or without IL-1beta or insulin-like growth factor I (IGF-I). Stromelysin activity and stromelysin quantitation were assayed by spectrofluorometry and enzyme amplified sensitivity immunoassay (EASIA), respectively. Proteoglycans (PG) were quantified using a radioimmunoassay. Newly synthesized glycosaminoglycans (GAGs) were quantified by labeled sulfate (Na2(35)SO4) incorporation. This method allowed the PG size after exclusion chromatography to be determined. Strontium ranelate, calcium ranelate, and SrCl2 did not modify stromelysin synthesis even in the presence of IL-1beta. Calcium ranelate induced stromelysin activation whereas strontium compounds were ineffective. Strontium ranelate and SrCl2 both strongly stimulated PG production suggesting an ionic effect of strontium independent of the organic moiety. Moreover, 10(-3) M strontium ranelate increased the stimulatory effect of IGF-I (10(-9) M) on PG synthesis but did not reverse the inhibitory effect of IL-1beta. Strontium ranelate strongly stimulates human cartilage matrix formation in vitro by a direct ionic effect without stimulating the chondroresorption processes. This finding provides a preclinical basis for in vivo testing of strontium ranelate in OA. PMID- 11204432 TI - Antagonism of the osteoclast vitronectin receptor with an orally active nonpeptide inhibitor prevents cancellous bone loss in the ovariectomized rat. AB - An orally active, nonpeptide Arg-Gly-Asp (RGD) mimetic alpha(v)beta3 antagonist, (S)-3-Oxo-8-[2-[6-(methylamino)-pyridin-2-yl]-1-ethoxy]-2-(2,2,2-trifluoroethyl) 2,3,4,5-tetrahydro-1H-2-benzazepine-4-acetic acid (compound 1), has been generated, which prevented net bone loss and inhibited cancellous bone turnover in vivo. The compound binds alpha(v)beta3 and the closely related integrin alpha(v)beta5 with low nanomolar affinity but binds only weakly to the related integrins alpha(IIb)beta3, and alpha5beta1. Compound 1 inhibited alpha(v)beta3 mediated cell adhesion with an IC50 = 3 nM. More importantly, the compound inhibited human osteoclast-mediated bone resorption in vitro with an IC50 = 11 nM. In vivo, compound 1 inhibited bone resorption in a dose-dependent fashion, in the acute thyroparathyroidectomized (TPTX) rat model of bone resorption with a circulating EC50 approximately 20 microM. When dosed orally at 30 mg/kg twice a day (b.i.d.) in the chronic ovariectomy (OVX)-induced rat model of osteopenia, compound 1 also prevented bone loss. At doses ranging from 3 to 30 mg/kg b.i.d., compound 1 partially prevented the OVX-induced increase in urinary deoxypyridinoline. In addition, the compound prevented the OVX-induced reduction in cancellous bone volume (BV), trabecular number (Tb.N), and trabecular thickness (Tb.Th), as assessed by quantitative microcomputerized tomography (microCT) and static histomorphometry. Furthermore, both the 10-mg/kg and 30 mg/kg doses of compound prevented the OVX-induced increase in bone turnover, as measured by percent osteoid perimeter (%O.Pm). Together, these data indicate that the alpha(v)beta3 antagonist compound 1 inhibits OVX-induced bone loss. Mechanistically, compound 1 prevents bone loss in vivo by inhibiting osteoclast mediated bone resorption, ultimately preventing cancellous bone turnover. PMID- 11204433 TI - T cell activation induces human osteoclast formation via receptor activator of nuclear factor kappaB ligand-dependent and -independent mechanisms. AB - In unstimulated conditions, osteoclast (OC) formation is regulated by stromal cell production of the key osteoclastogenic factors receptor activator of nuclear factor kappaB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). However, the mechanisms of accelerated osteoclastogenesis and bone loss characteristic of inflammatory conditions are poorly understood but appear to involve T cells. In addition, the mechanism by which OCs arise spontaneously in cultures of peripheral blood mononuclear cells in the absence of stromal cells or added cytokines remains unclear. Using a stromal cell free human osteoclast generating system, we investigated the ability of activated T cells to support osteoclastogenesis. We show that when activated by phytohemagglutinin-P (PHA), T cells (both CD4+ and CD8+) stimulate human OC formation in vitro. Although both soluble M-CSF and RANKL were detected in activated T cell supernatants, the presence of M-CSF was not essential for macrophage survival or RANKL-dependent osteoclast formation, suggesting that other soluble T cell-derived factors were capable of substituting for this cytokine. We also found that saturating concentrations of osteoprotegerin (OPG) failed to neutralize 30% of the observed OC formation and that T cell conditioned medium (CM) could superinduce osteoclastogenesis in cultures of purified monocytes maximally stimulated by RANKL and M-CSF. Together, these data suggest that activated T cells support osteoclastogenesis via RANKL-dependent and -independent mechanisms. Although not relevant for T cell-induced osteoclastogenesis, secretion of soluble M-CSF is a previously undescribed property of activated T cells. PMID- 11204434 TI - Efficacy of etanercept for wear debris-induced osteolysis. AB - A major limitation of total joint arthroplasty is that up to 20% of patients require revision surgery to correct prosthetic loosening. Aseptic loosening is believed to result from the phagocytosis of wear debris particles by macrophages, which secrete proinflammatory cytokines that stimulate osteolysis. Tumor necrosis factor alpha (TNF-alpha) has been shown to be one of the prominent cytokines in this cascade and to be involved critically in the generation of particle-induced osteolysis. Etanercept is a soluble inhibitor of TNF-alpha, which is widely used for the treatment of rheumatoid arthritis. Here, we show this agent's ability to prevent wear debris-induced osteolysis. In vitro we show that Etanercept can inhibit directly osteoclastic bone resorption in a bone wafer pit assay, as well as cytokine production from titanium (Ti)-stimulated macrophages. Using a quantitative in vivo model of wear debris-induced osteolysis, we show that Etanercept prevents bone resorption and osteoclastogenesis. In mice treated with Etanercept at the time of osteolysis induction, bone resorption and osteoclast numbers were reduced to background levels in both normal and human TNF-alpha (hTNF-alpha) transgenic mice. In an effort to evaluate its effect on established osteolysis, Etanercept was administered 5 days after Ti implantation, and we observed that further osteolysis was prevented. These data support the concept that TNF-alpha is involved critically in osteoclastogenesis and bone resorption during periprosthetic osteolysis and suggest that soluble TNF-alpha inhibitors may be useful as therapeutic agents for the treatment of prosthetic loosening in humans. PMID- 11204435 TI - The effect of a single dose of osteoprotegerin in postmenopausal women. AB - Osteoprotegerin (OPG), a tumor necrosis factor (TNF) receptor family member, is a critical regulator of bone resorption. It is an important inhibitor of the terminal differentiation and activation of osteoclasts. This randomized, double blind, placebo-controlled, sequential dose escalation study was conducted in postmenopausal women to determine the effect of a single subcutaneous (s.c.) dose of OPG on bone resorption as indicated by the biochemical markers, urinary N telopeptide (NTX) and deoxypyridinoline (DPD), which are stable collagen degradation products. NTX levels decreased within 12 h after OPG administration. At the highest dose administered (3.0 mg/kg), a mean percent decrease in NTX of approximately 80% was observed 4 days after dosing. Six weeks after dosing a mean decrease of 14% in NTX was observed. The levels of bone-specific alkaline phosphatase (BSAP), a marker of bone formation, did not change for approximately 3 weeks after dosing. Thereafter, a modest decrease, reaching approximately 30% at 6 weeks, was observed in the 3.0-mg/kg dose group. The rapid decrease from baseline in NTX and delayed decrease in BSAP indicated that OPG acted primarily on osteoclasts to decrease bone resorption. OPG injections are well tolerated. This study, for the first time, indicates that a single s.c. injection of OPG is effective in rapidly and profoundly reducing bone turnover for a sustained period and that OPG therefore may be effective in treatment of bone diseases characterized by increased bone resorption such as osteoporosis. PMID- 11204436 TI - Indapamide, a thiazide-like diuretic, decreases bone resorption in vitro. AB - We recently showed that indapamide (IDP), a thiazide-related diuretic, increases bone mass and decreases bone resorption in spontaneously hypertensive rats supplemented with sodium. In the present study, we evaluated the in vitro effects of this diuretic on bone cells, as well as those of hydrochlorothiazide (HCTZ), the reference thiazide, and acetazolamide (AZ), a carbonic anhydrase (CA) inhibitor. We showed that 10(-4) M IDP and 10(-4) M AZ, as well as 10(-5) M pamidronate (APD), decreased bone resorption in organ cultures and in cocultures of osteoblast-like cells and bone marrow cells in the presence of 10(-8) M 1,25 dihydroxyvitamin D3 [1,25(OH)2D3]. We investigated the mechanism of this antiresorptive effect of IDP; IDP decreased osteoclast differentiation as the number of osteoclasts developing in coculture of marrow and osteoblast-like cells was decreased markedly. We then investigated whether IDP affected osteoblast-like cells because these cells are involved in the osteoclast differentiation. Indeed, IDP increased osteoblast-like cell proliferation and alkaline phosphatase (ALP) expression. Nevertheless, it did not modify the colony-stimulating factor 1 (CSF 1) production by these cells. In addition, osteoblast-like cells expressed the Na+/Cl- cotransporter that is necessary for the renal action of thiazide diuretics, but IDP inhibited bone resorption in mice lacking this cotransporter, so the inhibition of bone resorption and osteoclast differentiation did not involve this pathway. Thus, we hypothesized that IDP may act directly on cells of the osteoclast lineage. We observed that resorption pits produced by spleen cells cultured in the presence of soluble osteoclast differentiation factor (sODF) and CSF-1 were decreased by 10(-4) M IDP as well as 10(-5) M APD. In conclusion, in vitro IDP increased osteoblast proliferation and decreased bone resorption at least in part by decreasing osteoclast differentiation via a direct effect on hematopoietic precursors. PMID- 11204437 TI - Genetic contribution to bone metabolism, calcium excretion, and vitamin D and parathyroid hormone regulation. AB - A classical twin study was performed to assess the relative contribution of genetic and environmental factors to bone metabolism, calcium homeostasis, and the hormones regulating them. It was examined further whether the genetic effect is menopause dependent. The subjects were 2136 adult twins (98.3% female): 384 monozygotic (MZ) and 684 dizygotic (DZ) twin pairs. The intraclass correlations were calculated, and maximum likelihood model fitting was used to estimate genetic and environmental variance components. The intraclass correlations for all of the variables assessed were higher in MZ twin pairs. The heritabilities (95% CIs) obtained from model fitting for hormones regulating bone metabolism and calcium homeostasis were parathyroid hormone (PTH), 60% (54-65%); 25 hydroxyvitamin D [25(OH)D]; 43% (28-57%), 1,25-hydroxyvitamin D [1,25(OH)], 65% (53-74%); and vitamin D binding protein 62% (56-66%). The heritabilities (95% CIs) for markers of bone formation also were assessed; bone-specific alkaline phosphatase (BSAP), 74% (67-80%), and osteocalcin, 29% (14-44%); marker of bone resorption deoxypyridinoline (DPD), 58% (52-64%); and measure of calcium homeostasis 24 h urine calcium, creatinine (Cr), 52% (41-61%). The magnitude of genetic influence differed with menopause for most variables. This study provides evidence for the importance of genetic factors in determining bone resorption and formation, calcium excretion, and the hormones regulating these processes. It shows for the first time a clear genetic effect on bone resorption in premenopausal women and the regulation of PTH, vitamin D metabolism, and calcium excretion. The genes controlling bone hormones and markers are likely to be useful therapeutic and diagnostic targets. PMID- 11204438 TI - Interaction between the vitamin D receptor gene and collagen type Ialpha1 gene in susceptibility for fracture. AB - Osteoporosis is a common disease with a strong genetic component. Polymorphisms in the vitamin D receptor (VDR) gene have been implicated in osteoporosis but explain only a small part of the genetic effect on bone mineral density (BMD) while their effect on fractures is still uncertain. Recently, a G to T polymorphism in an Sp1 site in the collagen type Ialpha1 (COLIA1) gene was found to be associated with reduced BMD and with increased fracture risk. To analyze the combined influence of polymorphisms in the VDR gene and the COLIA1 gene in determining the susceptibility to osteoporotic fracture, we studied 1004 postmenopausal women. The "baT" VDR haplotype, constructed from three adjacent restriction fragment length polymorphisms, was found to be overrepresented among fracture cases (p = 0.009). This corresponded to an odds ratio (OR) of 1.8 (95% CI, 1.0-3.3) for heterozygous carriers and 2.6 (95% CI, 1.4-5.0) for homozygous carriers of the risk haplotype. The effect was similar for vertebral and nonvertebral fractures and, most importantly, independent of BMD. We observed significant interaction (p = 0.03) between VDR and COLIA1 genotype effects. Fracture risk was not VDR genotype-dependent in the COLIA1 "reference" group (genotype GG) while in the COLIA1 "risk" group (genotypes GT and TT) the risk of fracture was 2.1 (95% CI, 1.0-4.4) for heterozygous and 4.4 (95% CI, 2.0-9.4) for homozygous carriers of the VDR risk haplotype. We conclude that both the VDR and the COLIA1 polymorphisms are genetic markers for osteoporotic fracture in women, independent of BMD. Our data indicate that interlocus interaction is likely to be an important component of osteoporotic fracture risk. PMID- 11204439 TI - Postnatal and pubertal skeletal changes contribute predominantly to the differences in peak bone density between C3H/HeJ and C57BL/6J mice. AB - Previous studies have shown that 60-70% of variance in peak bone density is determined genetically. The higher the peak bone density, the less likely an individual is to eventually develop osteoporosis. Therefore, the amount of bone accrued during postnatal and pubertal growth is an important determining factor in the development of osteoporosis. We evaluated the contribution of skeletal changes before, during, and after puberty to the development of peak bone density in C3H/HeJ (C3H) and C57BL/6J (B6) mice. Volumetric bone density and geometric parameters at the middiaphysis of femora were measured by peripheral quantitative computed tomography (pQCT) from days 7 to 56. Additionally, biochemical markers of bone remodeling in serum and bone extracts were quantified. Both B6 and C3H mice showed similar body and femoral weights. B6 mice had greater middiaphyseal total bone area and thinner cortices than did C3H mice. Within strains, males had thicker cortices than did females. C3H mice accumulated more minerals throughout the study, with the most rapid accumulation occurring postnatally (days 7-23) and during pubertal maturation (days 23-31). C3H mice had higher volumetric bone density as early as day 7, compared with B6 mice. Higher serum insulin-like growth factor I (IGF-I) was present in C3H mice postnatally at day 7 and day 14. Until day 31, B6 male and female mice had significantly higher serum osteocalcin than C3H male and female mice, respectively. Alkaline phosphatase (ALP) was found to be significantly higher in the bone extract of C3H mice compared with B6 mice at day 14. These data are consistent with and support the hypothesis that the greater amount of bone accrued during postnatal and pubertal growth in C3H mice compared with B6 mice may be caused by increased cortical thickness, increased endosteal bone formation, and decreased endosteal bone resorption. PMID- 11204440 TI - The influence of growth hormone deficiency, growth hormone replacement therapy, and other aspects of hypopituitarism on fracture rate and bone mineral density. . AB - To assess the influence of factors affecting fracture risk and bone density in adult hypopituitary patients with growth hormone deficiency (GHD), data from a large-scale pharmacoepidemiological survey (the Pharmacia & Upjohn International Metabolic Database [KIMS]) were analyzed and compared with data from a control population (the European Vertebral Osteoporosis Study [EVOS]). The KIMS group consisted of 2084 patients (1112 men and 972 women) with various types of pituitary disease and EVOS consisted of 1176 individuals (581 men and 595 women). Fracture and bone mineral density (BMD) data were available from 2024 patients from the KIMS group and 392 patients from EVOS. The prevalence of fractures in patients with hypopituitarism was 2.66 times that in the non-GH-deficient EVOS population. Adult-onset hypopituitarism with GHD was associated with a higher fracture risk than childhood-onset disease, and patients with isolated GHD had a similar prevalence of fractures to those with multiple pituitary hormone deficiencies. Hormonal replacement therapy with L-thyroxine, glucocorticoids, and sex steroids did not affect the risk of fracture in KIMS patients. In addition, fracture rates in KIMS were independent of body mass index (BMI) and the country of origin. However, smoking was associated with a higher fracture rate in this group. In summary, this is the first large-scale analysis to support the hypothesis of an increased fracture risk in adult patients with hypopituitarism and GHD. This increased risk appears to be attributable to GHD alone, rather than to other pituitary hormone deficiencies or to their replacement therapy. PMID- 11204441 TI - Quantitative ultrasound and bone mineral density are equally strongly associated with risk factors for osteoporosis. AB - Because resources do not allow all women to be screened for osteoporosis, clinical risk factors are often used to identify those individuals at increased risk of fracture who are then assessed by bone densitometry. The aim of this study was to compare calcaneal quantitative ultrasound (QUS) and axial bone mineral density (BMD) T and Z scores in a large group of women, some with no clinical risk factors and others with one or more risk factors for osteoporosis. The study population consisted of 1115 pre- and postmenopausal women. A subgroup of 530 women was used to construct reference data for calculating T and Z scores. A total of 786 women was found to have one or more of the following risk factors: (i) atraumatic fracture since the age of 25 years, (ii) report of X-ray osteopenia, (iii) predisposing medical condition or use of therapy known to affect bone metabolism, (iv) premature menopause before the age of 45 years or a history of amenorrhea of longer than 6 months duration, (v) family history of osteoporosis, (vi) body mass index (BMI) <20 kg/m2, and (vii) current smoking habit. Calcaneal broadband ultrasound attenuation (BUA) and speed of sound (SOS) measurements were performed on a Hologic Sahara and a DTUone and BMD was measured at the spine and hip using dual-energy X-ray absorptiometry (DXA). The Z score decrements associated with the seven risk factors calculated using multivariate regression analysis were similar for QUS and BMD measurements. Z score decrements (mean of BMD and QUS measurements combined) associated with a history of atraumatic fracture (-0.67), X-ray osteopenia (-0.36), a family history of osteoporosis (-0.23), and a low BMI (-0.53) were all statistically significant compared with women with no risk factors. Z score decrements associated with a medical condition or use of therapy known to affect bone metabolism, a premature menopause or prolonged amenorrhea, or those who were current smokers were not significantly different from zero. As the number of risk factors present in each individual increased, the mean Z score decrements became more negative, increasing from -0.28 for women with one risk factor to -1.19 for those with four or more risk factors. QUS and BMD measurements yielded similar mean Z scores for women with one, two, three, or more than four risk factors. Using the World Health Organization (WHO) criteria to diagnose osteoporosis for BMD measurements and revised diagnostic criteria for QUS, approximately one-third of postmenopausal women aged 50+ years with clinical risk factors were classified as osteoporotic compared with only 12% of women without clinical risk factors. Over two-thirds of postmenopausal women with risk factors were classified as osteopenic or osteoporotic and approximately 28% were classified as normal. The proportion of women classified into each diagnostic category was similar for BMD and QUS. In conclusion, clinical risk factors for osteoporosis affected calcaneal BUA and SOS Z score measurements to the same extent as axial BMD Z score measurements. Provided revised diagnostic criteria are adopted for QUS, similar proportions of postmenopausal women are identified as osteopenic or osteoporotic as with BMD. PMID- 11204442 TI - Inaccuracies inherent in patient-specific dual-energy X-ray absorptiometry bone mineral density measurements: comprehensive phantom-based evaluation. AB - An extensive series of dual-energy X-ray absorptiometry (DXA) scans and dual polyenergetic X-ray simulation studies of 150 different phantom arrays were carried out to evaluate quantitatively the extent of systematic inaccuracies inherent in DXA in vivo bone mineral density (BMD). These measurements are particularly relevant to lumbar vertebral and proximal femoral sites. The phantoms were specially fabricated near perfect absorptiometric representations of bone material, red marrow (RM) and yellow marrow (YM), and extraosseous mixtures of fat (F) and lean muscle that spanned the full range of soft tissue anthropometrics encountered clinically. In each case, the DXA-measured BMD values obtained using Hologic, Lunar, and Norland densitometers were found to be virtually the same and to be in excellent agreement with the corresponding quantitative simulation study BMD results. Comparisons of the known phantom BMD values and DXA-measured BMD in each case allowed the BMD inaccuracies to be evaluated. These present findings show that these ubiquitous inaccuracies in DXA BMD methodology are of in vivo soft tissue anthropometric genesis. It is found that patient-specific DXA-measured in vivo BMD inaccuracies as high as 20% or more can be readily anticipated clinically, particularly in cases of osteopenic, osteoporotic, and elderly patients. As these inaccuracies exceed considerably DXA precision errors, they may compromise patient-specific evaluations of fracture risk and, in prospective studies, mask or exaggerate clinically significant true changes in BMD. It is concluded that the magnitudes and variability of inherent inaccuracies in DXA-measured in vivo BMD underscore the need for prudence and circumspection in interpretations and assessments of DXA-based clinical studies. PMID- 11204443 TI - Nitric oxide up-regulates DNA-binding activity of nuclear factor-kappaB in macrophages stimulated with silica and inflammatory stimulants. AB - Nitric oxide (NO), a reactive nitrogen species, plays an important role in inflammatory lung damage. In the present study, we investigated the role of NO in DNA-binding activity of NF-kappaB in macrophages stimulated with silica or other inflammatory stimulants. Treatment of mouse macrophages (RAW264.7 cells) with a selective inhibitor of inducible nitric oxide synthase (iNOS), L-N6-(1 iminoethyl) lysine (L-NIL), or a nonselective iNOS inhibitor, N omega-nitro-L arginine methylester (L-NAME), resulted in inhibition of silica-induced nitric oxide production as well as silica-induced NF-kappaB activation. L-NIL also effectively inhibited NF-kappaB activation induced by other inflammatory stimulants, such as lipopolysaccharide (LPS) or muramyl dipeptide (MDP). These inhibitory effects of L-NIL and L-NAME on silica- or LPS-induced NF-kappaB activation were also observed in primary rat alveolar macrophages. Furthermore, NO generating compounds, such as sodium nitroprusside (SNP) and 3 morpholinosydnonimine (SIN-1), caused a dose-dependent increase in NF-kappaB activation, which was positively correlated with the level of NO production. Specific inhibitors of protein tyrosine kinase, such as genistein and AG494, prevented NF-kappaB activation in SNP- or SIN-1 treated cells, suggesting involvement of tyrosine kinase in the NO signaling pathway leading to NF-kappaB activation. In contrast, inhibitors of protein kinase C or A, such as staurosporine or H89, had no inhibitory effect on SIN-1 induced NF-kappaB activation. Metalloporphyrins, such as tetrakis (N-methyl-4'-pyridyl) porphyrinato iron (III) (Fe-TMPyP) and Zn-TMPyP which are known to alter NO dependent activity, markedly inhibited silica- and LPS-induced NF-kappaB activation. The results suggest that NF-kappaB activation in macrophages can be induced under certain conditions by nitric oxide and that nitric oxide produced by phagocytes exposed to inflammatory agents may up-regulate the activation of NF kappaB. PMID- 11204444 TI - Mechanical stretch augments PDGF receptor beta expression and protein tyrosine phosphorylation in pulmonary artery tissue and smooth muscle cells. AB - With regard to the mechanotransduction mechanisms of vasculature involved in hypertensive diseases, we aimed to identify tyrosine-phosphorylated proteins in pulmonary artery that responded to mechanical stress. Mechanical stretch simultaneously augmented protein-tyrosine phosphorylation in p55, p95, p105, p115, p130, p165, p180 in pulmonary artery tissue and pulmonary artery-derived smooth muscle cells (PASMC), whereas p115 and p55 were preferentially phosphorylated by the stretch in endothelial cells (PAEC). A series of experiments designed to characterize these proteins indicated that p115 and p180 were focal adhesion kinase (FAK) and platelet-derived growth factor receptor beta (PDGF-Rbeta), respectively, and that stretch augmented the surface-expression of PDGF-Rbeta in PASMC but not in PAEC. Moreover, a significant increase in the steady-state mRNA level for PDGF-Rbeta was observed in the pulmonary artery of rats with monocrotaline-induced pulmonary hypertension, where the artery should be overstretched due to increasing pulmonary arterial blood pressure. These results suggest that stretch-induced overexpression of cell-surface PDGF-Rbeta as well as augmentation of yrosine phosphorylation of proteins including FAK in PASMC might be involved in the mechanotransduction of pulmonary artery. PMID- 11204445 TI - Ontogenic profile of some antioxidants and lipid peroxidation in human placental and fetal tissues. AB - Reactive oxygen species (ROS) pose a serious threat to maternal and fetal health during pregnancy. However, there is little information on the oxidative damage caused by ROS and its protection during prenatal life. The present study highlights the status of various antioxidants in human placental and fetal tissues at different phases of gestation. The activity profile of scavenging enzymes, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase as well as the concentrations of non-enzymatic antioxidants, ascorbic acid, alpha-tocopherol, bilirubin and glutathione have been determined in human placental whole homogenate, placental brush border membrane and fetal liver over gestational periods ranging from 6 weeks of pregnancy till birth. The ontogenic profile of lipid peroxidation, a marker of oxidative damage has also been investigated in the feto-placental system. Catalase, superoxide dismutase and glutathione reductase activities increased significantly, but glutathione peroxidase activity remained almost the same throughout development. Except alpha tocopherol and bilirubin, the concentrations of other non-enzymic scavengers followed a significant increasing trend with advancement of pregnancy. Results indicate that there is gradual suppression of lipoperoxide formation with the progress of gestation to protect the fetus against oxygen toxicity. PMID- 11204446 TI - Hexokinase 'binding sites' of normal and tumoral human brain mitochondria. AB - Interaction of type I hexokinase (HK-I) with the mitochondria obtained from the biopsy specimens of normal and tumoral human brain tissues was studied in the present investigation. This effort was undertaken with the aim of exploring possible differences in the mode of association of the enzyme with the outer mitochondrial membrane in the described sources. Results indicate that the two 'sites' for binding of HK-I suggested in the literature, based on extensive studies carried out on rat brain mitochondria, are similarly present in the human brain mitochondria. Differences in the microenvironments of HK binding, as reflected by the presented data, are suggested to be of importance in regulation of the catalytic potential of the bound enzyme. The real metabolic significance of this association in relation to cancer and its practical importance would need further investigation. PMID- 11204447 TI - Chlamydia pneumoniae infection significantly exacerbates aortic atherosclerosis in an LDLR-/- mouse model within six months. AB - We have previously shown that infection with the C. pneumoniae AR39 strain once monthly for 9 consecutive months significantly exacerbated atherosclerosis in mice with LDL receptor deficiency (LDLR-/-) in the presence of a high cholesterol diet. To further optimize the LDLR-/- mouse model for studying the mechanisms of C. pneumoniae atherogenesis, we have tested a different infection protocol with intranasal inoculation twice monthly for 6 consecutive months in the present study. We found that C. pneumoniae infection for 6 months was sufficient to produce a 130%, significantly greater exacerbation of aortic atherosclerosis in LDLR-/- mice in the presence of a high cholesterol diet. Mice receiving a high cholesterol diet alone displayed a lesion area index of 18.2 +/- 6.1 (S.D.) while mice treated with both the high cholesterol diet and C. pneumoniae infection had a lesion area index of 41.8 +/- 15.2 (S.D.). However, the chlamydial infection did not significantly alter the mouse serum total cholesterol or the LDL levels induced by the high cholesterol diet. This study not only confirms our previous findings that C. pneumoniae infection can exacerbate aortic atherosclerosis lesion in the LDLR-/- mice, but also further optimizes the LDLR-/- mouse model for future mechanism studies. PMID- 11204448 TI - Salutary effect of tedisamil on post-ischemic recovery rat heart: involvement of sarcolemmal (Na,K)-ATPase. AB - The in vitro effect of tedisamil on the specific activity and kinetic parameters of the sarcolemmal (Na,K)-ATPase as well as its ex vivo effect on the (Na,K) ATPase in the isolated, perfused rat hearts was determined. Five micromol/l of tedisamil was added 5 min before the onset of 30 min global normothermic ischemia followed by 10 min reperfusion. At the conditions of its maximal cardioprotective effect (heart rate reduction, improved postischemic recovery of left ventricular developed pressure), the hearts were immediately used for isolation of sarcolemmal vesicles. In vitro, 1-100 micromol/l of tedisamil produced a concentration-dependent stimulatory effect on (Na,K)-ATPase activity, with a peak seen at 20 micromol/l (p < 0.01), while Mg-dependent ATPase was almost unchanged. Kinetic analysis revealed a significant increase in the affinity of the Na binding sites on ATPase molecule at 20 micromol/l of tedisamil. These biochemical findings were confirmed by cytochemistry. Moreover, ex vivo experiments revealed that tedisamil rendered the sarcolemmal (Na,K)-ATPase activity to be a more resistant to detrimental effects of ischemia. In conclusion, the cardioprotective action of tedisamil was accompanied with a better preservation of the specific activity of (Na,K)-ATPase. PMID- 11204449 TI - The regulation of CoA-independent transacylation reactions in neuronal nuclei by lysophospholipid, free fatty acid, and lysophospholipase: the control of nuclear lyso platelet-activating factor metabolism. AB - CoA-independent transacylase activities generating alkylacylglycerophosphocholine (AAGPC) from alkylglycerophosphocholine (1-alkyl GPC) were considerably enriched in neuronal nuclei isolated from rabbit cerebral cortex. Specific nuclear transacylation activities were 13 times the corresponding microsomal values. Several lysophospholipids, notably 1-acyl glycerophosphocholine (1-acyl GPC), 1 alkenyl GPC and 1-alkenyl GPE (1-alkenyl glycerophosphoethanolamine) inhibited the transacylation of 1-alkyl GPC. The inhibitory effects of 1-acyl GPC were seen in the presence of MAFP (methyl arachidonoylfluorophosphonate) or free oleate, compounds that inhibit neuronal nuclear lysophospholipase. When neuronal nuclei were preincubated with 1-alkyl GPC, the radioactive AAGPC product served as donor in transacylation reactions, to generate 1-alkyl GPC. In these nuclear reactions, 1-palmitoyl GPE and 1-palmitoyl GPC appeared to be poor acceptor substrates, when compared with corresponding 1-alkyl and 1-alkenyl analogues. The presence of free oleate or MAFP in the reactions containing 1-acyl GPC boosted the release of 1 alkyl GPC from AAGPC. These observations are of particular relevance to brain ischemia in which lysophospholipid, free fatty acid, and platelet-activating factor (PAF) levels rise dramatically. PAF can be made by the nuclear acetylation of 1-alkyl GPC, which is formed by nuclear transacylation mechanisms. Yet transacylase also removes 1-alkyl GPC, and thus this enzyme activity can regulate 1-alkyl GPC availability. Our observations indicate that lysophospholipids promote the formation of 1-alkyl GPC from nuclear AAGPC via transacylation, while free fatty acid likely prolongs the lifetime of 1-acyl lysophospholipids substrates by lysophospholipase inhibition. Similarly, once 1-alkyl GPC is formed, other lysophospholipids effectively compete with this 1-alkyl analogue and reduce its conversion back to AAGPC by transacylation. Free oleate, in this case, sustains 1-acyl lysophospholipid inhibitors of 1-alkyl GPC transacylation. Thus the cycle of transacylation may favour 1-alkyl GPC formation during ischemia, increasing levels of 1-alkyl GPC for nuclear acetylation reactions and PAF formation. The nuclear generation of PAF is of considerable importance as PAF can play regulatory roles in transcription events associated with inflammation. PMID- 11204450 TI - Free radicals, cytokines and nitric oxide in cardiac failure and myocardial infarction. AB - Myocardial infarction is the most common cause of congestive cardiac failure. Free radicals, cytokines, nitric oxide (NO) and antioxidants play a major role both in atherosclerosis and myocardial damage and preservation. In the early stages of atherosclerosis, neutrophils and monocytes infiltrate the intima and generate free radicals which damage the endothelial cells. As a result, production of NO and prostacyclin by the endothelial cells declines, which have cardioprotective actions. This also has relevance to the beneficial action of aspirin since, it can modulate both prostanoid and L-arginine-NO systems and NF kB translocation. In both acute myocardial infarction and chronic congestive cardiac failure, the plasma levels of various inflammatory mediators such as interleukins and tumour necrosis factor-alpha (TNFalpha) are elevated. TNFalpha, produced by the inflammatory cells and the myocardium, can suppress myocardial contractility and induce the production of free radicals, which in turn can further damage the myocardium. Transforming growth factor beta (TGFbeta), polyunsaturated fatty acids and the glucose-insulin-potassium regimen can antagonize the harmful actions of TNFalpha and protect the myocardium. This explains why efforts made to reduce the levels of pro-inflammatory cytokines have beneficial action and preserve the myocardium. PMID- 11204451 TI - Green fluorescent protein as a marker for monitoring activity of stress-inducible hsp70 rat gene promoter. AB - Murine melanoma cells B16(F10) were stably transfected with a plasmid containing GFP gene linked to rat stress-inducible hsp70.1 gene promoter. Transfected cells show in vitro variable basal levels of fluorescence depending on stress response induced at physiological temperature by growth conditions. Lack of manipulations except medium change resulted in reduction of cellular fluorescence. GFP expression in experimental murine tumors dropped to levels undetectable at physiological temperature. Heat shock induced significant fluorescence of tumor cells both in vitro and in vivo. GFP protein could be a useful marker for studies of mammalian hsp70i gene promoters. PMID- 11204452 TI - Gender-related differences in proliferative response of cardiac fibroblasts to hypoxia: effects of estrogen. AB - Ischemic heart disease is more prevalent in men than in women. The remodeling of extracellular matrix, is a structural correlate of heart failure of ischemic origin and proliferation of cardiac fibroblasts is a key factor in this remodeling. We asked if proliferative response of male and female cardiac fibroblasts is differentially susceptible to hypoxia. DNA synthesis, using 3H thymidine incorporation was compared under hypoxia (2% O2) in cardiac fibroblasts obtained from adult, age-matched male and female rat heart. In female cells DNA synthesis remained unchanged under hypoxia and this resistance was dependent on tyrosine kinase activation, as it was abolished in the presence of genistein, a tyrosine kinase inhibitor. Male cells, on the other hand, were susceptible to hypoxia and their DNA synthesis was reduced significantly (70%, (p < 0.0001). This effect was partially reversed by inhibition of tyrosine kinase. Western analysis showed a higher abundance of tyrosine phosphorylated proteins in male cells compared to female cells as well as differences in molecular weight of basal and hypoxia-induced tyrosine-phosphorylated proteins between male and female cells. The presence of estrogen (17-beta estradiol, 10 nM) altered the response of both cells to hypoxia. In female cells the combined effect of hypoxia and estrogen led to inhibition of DNA synthesis, whereas in male cells estrogen partially reversed the hypoxia-induced inhibition of DNA synthesis (37% (p < 0.01) inhibition in the presence of estrogen vs. 70% (p < 0.0001) inhibition in the absence of estrogen). The effects of estrogen in male and female cells were mediated via estrogen receptors as they were reversed by the pure anti-estrogen, ICI 182,780. Western analysis of cell lysate showed hypoxia-induced increase in the level of estrogen receptor beta in both male and female cells. Gel shift analysis showed hypoxia-induced increase in cytoplasmic ERE (estrogen response element)-binding activity and decrease in nuclear ERE-binding in male cells. In female cells cytoplasmic and nuclear ERE-binding activities remained unchanged under hypoxia. Together, these data demonstrate that while female cells are resistant to hypoxia-induced inhibition in DNA synthesis, male cells are susceptible; intracellular pathways involving tyrosine phosphorylation are involved in the response of both cells; and estrogen, via estrogen-receptor dependent mechanisms, differentially alters the response of male and female cells to hypoxia. PMID- 11204453 TI - Myocardial ischemic preconditioning and mitochondrial F1F0-ATPase activity. AB - A short period of ischemia followed by reperfusion (ischemic preconditioning) is known to trigger mechanisms that contribute to the prevention of ATP depletion. In ischemic conditions, most of the ATP hydrolysis can be attributed to mitochondrial F1F0-ATPase (ATP synthase). The purpose of the present study was to examine the effect of myocardial ischemic preconditioning on the kinetics of ATP hydrolysis by F1F0-ATPase. Preconditioning was accomplished by three 3-min periods of global ischemia separated by 3 min of reperfusion. Steady state ATP hydrolysis rates in both control and preconditioned mitochondria were not significantly different. This suggests that a large influence of the enzyme on the preconditioning mechanism may be excluded. However, the time required by the reaction to reach the steady state rate was increased in the preconditioned group before sustained ischemia, and it was even more enhanced in the first 5 min of reperfusion (101 +/- 3.0 sec in preconditioned vs. 83.4 +/- 4.4 sec in controls, p < 0.05). These results suggest that this transient increase in activation time may contribute to the cardioprotection by slowing the ATP depletion in the very critical early phase of post-ischemic reperfusion. PMID- 11204454 TI - Role of anaerobiosis in virulence of Salmonella typhimurium. AB - Intestinal pathogens are exposed to various stress conditions during their infectious cycle. Anaerobiosis, one of such hostile condition, is offered by the host within gut and intestinal lumen, where survival, multiplication and entry into intestinal epithelial cells is priority for the invading pathogen. In the present study, a virulent strain of S. typhimurium (1402/84) was grown under anaerobic conditions and its virulence characteristics such as host cell binding, penetration and intracellular survival were compared with aerobic S. typhimurium. Anaerobically grown S. typhimurium showed significantly higher binding to immobilized mice enterocytes and intestinal mucus as compared to bacteria grown aerobically. Anaerobic bacteria also showed an early penetration of mucus and subsequent binding to underlying immobilized enterocytes, in vitro. Anaerobic S. typhimurium exhibited increased intracellular survival within spleen macrophages of mice and caused significantly higher fluid accumulation in ligated rabbit ileal loops as compared to aerobic bacteria. LD50 of anaerobic S. typhimurium was also observed to be 2 fold lower when compared to aerobic bacteria. Cell surface hydrophobicity of anaerobic S. typhimurium was also found to be significantly higher than aerobic bacteria. Thus, it appears that exposure of S. typhimurium to anaerobiosis results in its enhanced virulence, adhesion and penetration of host cells. PMID- 11204455 TI - Paracrine effects of a uterine agglutinin are mediated via the sialic acids present in the rat uterine endometrium. AB - A 32 kDa estrogen-induced, sialic acid-specific agglutinin (P-SAS) was isolated from rat endometrium in its proestrus stage. To investigate the functional importance of P-SAS in the uterine milieu, specific binding assays were carried out with 125I-labeled P-SAS and different cellular components of the uterus (epithelial, stromal and myometrial cells), that were isolated from different stages of the estrus cycle. The results indicate that although the protein is secreted from the epithelial cells in the estrogenic phase, it binds specifically to the stromal cells, especially to those isolated from the diestrus stage of the estrus cycle. The specific binding, however, is seen to decrease with the progression of pregnancy. Scatchard analysis performed with varying amounts of 125I-P-SAS in the presence of excess cold P-SAS revealed that the binding occurs with a Ka = 1.69 x 10(8) M(-1). As P-SAS binds specifically to sialic acids on the stromal cell surface, further characterization of the sialic acid molecule to which P-SAS binds was carried out by gas liquid chromatography (GLC). The studies revealed that P-SAS preferentially binds to N-glycolylneuraminic acid, which is attached to the penultimate sugar of the stromal cell surface glycoprotein chain via alpha2,6 linkage. As P-SAS is further known to be mitogenic, the effect of P SAS on cultured stromal cells was studied in vitro. The growth regulatory assays revealed that P-SAS induced 3H-thymidine uptake by stromal cells in culture. Thus, from the above observations, paracrine effects of P-SAS on the stromal cells and on the subsequent growth and development of the uterus can be assumed. PMID- 11204456 TI - Suppression of inositol phosphate release by cardiac myocytes isolated from fish oil-fed pigs. AB - Fatty acid composition of cardiac myocytes and release of inositol phosphates in pigs fed a fish oil supplemented diet was examined. Two groups of female pigs were fed diets supplemented with either 50 g/kg diet beef tallow (as control) or 50 g/kg diet fish oil (MaxEPA) rich in n-3 fatty acids. After 6 weeks of supplementation, the pigs were anesthetized and hearts were removed. Cardiac myocytes were isolated, lipid extracted and separated into non-polar and polar lipids by thin-layer chromatography. Fatty acid composition of individual neutral and polar lipid classes were examined by gas chromatography. To study the effect of membrane phospholipid modification on the phospholipase C (PLC) mediated release of inositol phosphates, cardiac myocytes were labelled with 4 microCi/mL myo-[2-(3)H]inositol for 48 h. After stimulation with epinephrine and phenylephrine, the water soluble [3H]inositol products were extracted, separated from [3H]inositol and [3H]glycerophosphoinositol by chromatography on Dowex AG 1 X8 and quantitated by scintillation counting. Cardiac myocytes isolated from fish oil-fed pigs had higher levels of n-3 polyunsaturated fatty acid in the non esterified fatty acid and phospholipid fraction. Similarly, these cardiac myocytes had increased level of n-3 fatty and decreased n-6 fatty acids in all the phospholipid fractions, PE, PC, P1 and PS (p < 0.05). After stimulation, the levels of [3H]inositol trisphosphate (IP3) and [3H]inositol tetrakisphosphate (IP4) in cardiac myocytes isolated from fish oil-fed pigs were significantly reduced (p < 0.05) compared to myocytes isolated from beef tallow fed-pigs. This study for the first time has utilised adult cardiac myocytes to demonstrate the effect of n-3 PUFA supplementation on cardiac myocyte phospholipid fatty acid composition and release of second messengers. PMID- 11204457 TI - Regulation of Na/K-ATPase beta1-subunit gene expression by ouabain and other hypertrophic stimuli in neonatal rat cardiac myocytes. AB - Partial inhibition of Na/K-ATPase by ouabain causes hypertrophic growth and regulates several early and late response genes, including that of Na/K-ATPase alpha3 subunit, in cultured neonatal rat cardiac myocytes. The aim of this work was to determine whether ouabain and other hypertrophic stimuli affect Na/K ATPase beta1 subunit gene expression. When myocytes were exposed to non-toxic concentrations of ouabain, ouabain increased beta1 subunit mRNA in a dose- and time-dependent manner. Like the alpha3 gene, beta1 mRNA was also regulated by several other well-known hypertrophic stimuli including phenylephrine, a phorbol ester, endothelin-1, and insulin-like growth factor, suggesting involvement of growth signals in regulation of beta1 expression. Ouabain failed to increase beta1 subunit mRNA in the presence of actinomycin D. Using a luciferase reporter gene that is directed by the 5'-flanking region of the beta1 subunit gene, transient transfection assay showed that ouabain augmented the expression of luciferase. These data support the proposition that ouabain regulates the beta1 subunit through a transcriptional mechanism. The effect of ouabain on beta1 subunit induction, like that on alpha3 repression, was dependent on extracellular Ca2+ and on calmodulin. Inhibitions of PKC, Ras, and MEK, however, had different quantitive effects on ouabain-induced regulations of beta1 and alpha3 subunits. The findings show that partial inhibition of Na/K-ATPase activates multiple signaling pathways that regulate growth-related genes, including those of two subunit isoforms of Na/K-ATPase, in a gene-specific manner. PMID- 11204458 TI - Neuronal glycolytic pathway impairment induced by HIV envelope glycoprotein gp120. AB - Neurological impairment is a common feature of Acquired Immunodeficiency Syndrome (AIDS); functional alterations have been reported both in central and peripheral nervous system and the Human Immunodeficiency Virus (HIV) envelope glycoprotein gp120 has been proposed as a neurotoxin acting through a calcium-dependent mechanism. On the other hand it has been reported that gp120 treatment also induce about a 20% decrease in the cerebral glucose utilization and in the cellular ATP levels. The reported observations were performed on experimental system where also non-neuronal cells where present; in order to evaluate whether a direct interaction between HIV proteins and neuronal cells takes place, we used a neuroblastoma cultures where only neuronal cells are present. We analysed the effects of gp120 on the N18TG2 neuroblastoma clone. Treatments were performed both on growing and confluent cultures. Short time treatment with gp120 of confluent cultures causes a 25% reduction in the level of neuron-specific enolase, resulting in a similar decrease of oxygen consumption. Long time exposure of growing cells also causes a reduction in cell survival. Furthermore, using a membrane-specific fluorescent probe we observed that gp120 produces an increase of membrane trafficking. These observations suggest a direct interaction between the viral envelope protein and neuronal cells, which results in an alteration of glycolytic metabolism. This alteration may be related to the neurologic impairments observed in AIDS patients. PMID- 11204461 TI - Selenium, boron, and germanium deficiency in the etiology of Kashin-Beck disease. AB - Concentrations of selenium (Se), boron (B), and germanium (Ge) were determined in scalp hair of children with Kashin-Beck disease (KBD), in healthy children in KBD disease endemic areas, and in healthy children in non-KBD areas. Mean Se, B, and Ge concentrations were low in children with KBD; in hair of healthy children in KBD areas, Se levels were normal but B and Ge levels were lower than in KBD-free areas. The hair levels of B and Ge were unaffected by selenium supplementation. It is suggested that B and Ge deficiency may be contributing factors in the etiology of KBD. PMID- 11204459 TI - Altered ornithine decarboxylase and S-adenosylmethionine decarboxylase expression and regulation in mouse fibroblasts transformed with oncogenes or constitutively active Mitogen-Activated Protein (MAP) kinase kinase. AB - In the present study, the expression and the regulation of ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) was examined in a series of oncogene transformed cell lines. The expression of both ODC and SAMDC was found to correlate with the nature of the oncogene expressed and with the resulting cellular phenotype expressed. This study demonstrates, for the first time, that the expression of both ODC and SAMDC increases as a function of cellular transformation and, in particular, as a function of malignant progression. Ras transformed cells were shown to express a unique regulatory mechanism whereby a co-ordinate up-regulation of the expression of both ODC and SAMDC occurs (via post-transcriptional stabilization of their mRNA transcripts) in the presence of protein synthesis inhibition. Altered expression (and regulation) of both ODC and SAMDC is suggested to constitute an important part of an altered growth regulatory program inherent to oncogene transformed cells, in particular, to transformed cells capable of malignant progression. PMID- 11204460 TI - The Translocon-Associated Protein beta (TRAPbeta) in zebrafish embryogenesis. I. Enhanced expression of transcripts in notochord and hatching gland precursors. AB - The normal translocation of nascent polypeptides into the lumen of the endoplasmic reticulum (ER) is thought to be aided in part by a translocon associated protein (TRAP) complex consisting of 4 protein subunits. The association of mature proteins with the ER and Golgi, or other intracellular locales, such as lysosomes, depends on the initial targeting of the nascent polypeptide to the ER membrane. A similar scenario must also exist for proteins destined for secretion. We have identified a member of the TRAP complex using a two hybrid screen to isolate proteins that bind to zebrafish (Danio) Ran binding protein 1. The polypeptide predicted from the largest open reading frame contains 183 amino acids with a 86 and 87% sequence identity to the TRAPbeta subunits in human and chicken, respectively. Sequence analysis identified a cleavable amino terminal signal peptide in the zebrafish TRAPbeta subunit and a region of the protein spans the membrane of the endoplasmic reticulum. A reverse transcriptase polymerase chain reaction assay showed that TRAPbeta mRNA is expressed in the developing zebrafish embryo. TRAPbeta mRNA is maternally supplied to the egg and is expressed constitutively throughout development and in the adult. This pattern of expression indicates that the message encoding part of the machinery targeting nascent polypeptides to the ER lumen is available at the onset of embryogenesis when the rate of translation increases exponentially over that occurring in the oocyte. In situ hybridization was used to test whether or not TRAPbeta transcripts might become localized and/or enriched in the developing embryo. Homogeneous staining is seen in the blastula and early gastrula stages. At mid-to late gastrula stages, however, the message becomes enriched in the developing notochord and polster, or hatching gland rudiment. The TRAPbeta gene, mapped using the LN54 mouse-zebrafish radiation hybrid panel to linkage group 19, resides next to a gene (Z15451) which has sequence homology to notch2 and vascular endothelial growth factor. TRAPbeta, however, does not appear to belong to a group of genes which are syntenic with orthologues or paralogues on human chromosomes. PMID- 11204462 TI - Selenium deficiency and hypothyroidism: a new etiology in the differential diagnosis of hypothyroidism in children. AB - Three female children presented with different clinical symptoms that could be related to impaired thyroid function. They underwent an accurate pediatric endocrinologic diagnosis. Laboratory tests revealed no pathological findings, except latent hypothyroidism and selenium deficiency. Hypothyroidism was diagnosed by elevated basal TSH and by a pathological i.v.-TRH-stimulation test. After treating the children with sodium selenite orally for 4 wk, their metabolism had returned to normal and we saw a marked improvement of all clinical symptoms. For the first time, we have been able to describe hypothyroidism caused exclusively by selenium deficiency, the pathophysiology of which may be expressed as a malfunction of human 5'-deiodinases. PMID- 11204463 TI - The apparent effect of iron supplementation on serum selenium levels in teenage pregnancy. AB - Numerous studies have suggested a significant role of selenium in the prevention of gynecological carcinoma. These were epidemiological and prospective in humans and therapeutic in laboratory animals. However, no studies have been reported regarding the normal serum selenium levels during pregnancy. The maternal total blood volume increases 30-50% during the second and third trimesters, resulting in lower measured serum levels for those metabolites, which are not increased significantly during pregnancy. A longitudinal study of the serum selenium levels in teenage pregnancy during the last two trimesters and 3 mo postpartum showed progressive elevation from 49 +/- 7 microg/dL after the 32nd week of pregnancy to 114 +/- 7 microg/dL at term, which was statistically significant (p < or = 0.001). Prenatal supplementation with 18 mg of iron per day prevented this elevation. The results of this study suggest that serum selenium levels in women normally double during pregnancy and this doubling is prevented by the minimal daily supplementation of 18 mg of iron, which may be due to increased absorption of selenium into the erythrocytes and incorporation into the glutathione peroxidase enzyme. PMID- 11204464 TI - Content of non-mercury-associated selenium in human tissues. AB - Recent studies have shown that at a higher mercury (Hg) burden, the molar ratio of selenium (Se) and Hg in tissues tends to approximate 1:1 by the formation of biologically largely inert adducts. From the toxicological standpoint, this trapping of free Hg is welcome. However, this binding of Se to Hg reduces the portion of Se in tissues, which is available for the formation of essential selenoenzymes like glutathione peroxidase, type I deiodase, and so forth and could result in a relative deficiency of Se. Therefore, we tried to determine the concentration of non-Hg-associated Se in several human tissues. As there is no proved trace method for the speciation of non-Hg-bound and Hg-bound Se in tissues, the total concentrations of Hg and Se were determined and the portion of non-Hg-associated Se was calculated by the difference of the molar concentrations of Se and Hg. For this investigation, the following tissues were obtained by autopsy from 133 adults: kidney cortex, thyroid gland, liver, spleen, cerebrum cortex, and pituitary gland. In no case was an occupational Hg burden known. The results confirm the assumption of a 1:1 association of Hg and Se in human tissues. The mean concentration of non-Hg-bound Se was calculated to 576 microg/kg in the kidney cortex, 363 microg/kg in the thyroid gland, 308 microg/kg in the liver, 205 microg/kg in the spleen, 111 microg/kg in the cerebrum cortex, and 545 microg/kg in the pituitary gland. In none of the cases under investigation in any tissue was the molar Se/Hg ratio below 1. This means that a total deficiency of non-Hg-bound Se could not be seen in this normal population, even at a higher Hg burden. Nevertheless, at a suboptimal Se supply like in Germany, any reduction of the part of Se, which is available for the formation of essential seleno-enzymes, should be avoided. Therefore, any additional Hg burden such as from dental amalgam should to be considered critically. The different distribution of Hg and Se in the body confirms that there is a controlled hierarchy in the Se supply of different organs, which tries to prevent a Se deficiency in organs with essential seleno-enzymes like the thyroid gland even under an suboptimal Se supply. PMID- 11204465 TI - Hyperlipidemia and type I 5'-monodeiodinase activity: regulation by selenium supplementation in rabbits. AB - Male New Zealand White rabbits were divided into three groups: (I) control, (II) high-fat-diet (HFD) fed, and (III) HFD fed + selenium supplemented. After 3 mo of treatment, there was a significant increase in serum cholesterol and triglycerides in the HFD-fed group as compared to the control. However in the selenium (Se)-supplemented group, the levels of serum cholesterol and triglycerides were significantly less as compared to group II. HFD feeding resulted in decreased serum Se levels, but supplementation of dietary Se along with HFD, as in group III, showed an apparent increase in its levels. The Se dependent glutathione peroxidase (GSH-Px) activity in the liver and the aorta increased significantly in HFD-fed animals and also showed an additional significant increase on Se supplementation. Both serum T3 and T4 levels showed a significant decrease on HFD feeding. However, supplementation of Se led to a significant increase in the levels of these parameters viz-a-viz HFD-fed animals. HFD feeding significantly decreased the activity of type I iodothyronine 5' deiodinase (5'-DI) in the liver from group II rats. On supplementation of Se along with HFD, the activity increased in the liver. However, there was no significant change in its activity in the aorta. The 5'-DI activity in the thyroid showed an opposite trend in comparison with peripheral tissues (i.e., liver). The important finding of this study is that in the hyperlipidemic state, deiodinase in the thyroid behaves in a different manner as compared to its activity in extrathyroidal tissues. PMID- 11204466 TI - Effect of dietary copper on selenium toxicity in Fischer 344 rats. AB - The purpose of this study was to investigate the ameliorating effects of dietary copper supplementation on selenium toxicity. Nine groups (n = 6) of weanling Fischer 344 female rats were randomly assigned to treatment groups and fed diets containing nontoxic levels of copper as CuCl2 and/or selenium as selenite or selenocystamine. Weight gain, liver and spleen weights, plasma lipid peroxidation, and liver selenium and copper content were analyzed after the 6-wk treatment period. Concentrations of up to 10 times the daily lethal dose of dietary selenium were well tolerated in rats supplemented with dietary copper. As the dietary level of selenium was increased, the ratio of selenium to copper measured in the liver decreased. In the groups of rats in which dietary copper supplementation was absent and dietary selenium was supplemented, copper stores in the liver remained unchanged from control values. Copper's protective effects from dietary selenium toxicity may come from the formation of a copper-selenide complex that renders both selenium and copper metabolically unavailable and nontoxic. PMID- 11204467 TI - Selenium altered the levels of lipids, lipid peroxidation, and sulfhydryl groups in straitum and thalamus of rat. AB - The effect of sodium selenite (0.05, 0.1, and 0.2 mg/kg body weight, i.p.) on the lipid levels (total lipids, phospholipids, cholesterol, gangliosides), thiobarbituric acid reactive substance (TBARS), and sulfhydryl group (-SH) in the striatum and thalamus of a male Wistar rat was studied after 7 d of treatment. The level of total lipids and cholesterol was significantly and dose-dependently elevated in the striatum and thalamus with 0.1 and 0.2 mg/kg of sodium selenite. However, the cholesterol level was significantly increased only with 0.2 mg/kg of sodium selenite in the thalamus. The level of phospholipids and gangliosides was more significant with 0.1 mg/kg of sodium selenite as compared to 0.2 mg. No significant alteration on the gangliosides level was observed in the thalamus with various doses of sodium selenite although the elevation with 0.2 mg dose was 25.9%. The content of TBARS was elevated dose dependently in striatum, but its level was depleted significantly with 0.1-mg/kg dose of sodium selenite in the thalamus. The level of the -SH group was significantly depleted in the striatum with 0.1-mg/kg dose of sodium selenite; conversely, this dose has significantly elevated the levels of -SH group in the thalamus. PMID- 11204468 TI - Microcalorimetric study of the toxic effect of sodium selenite on the mitochondria metabolism of Carassius auratus liver. AB - The fundamental thermogenesis curves of the metabolic process of liver mitochondria from Carassius auratus and the toxic effect of Na2SeO3 on it were studied by using an LKB-2277 bioactivity monitor, ampoule method, at 28 degrees C. From the thermogenesis curves, the thermokinetic equations were established under different conditions. The kinetics show that a low concentration of Na2SeO3 (1-4 mg/L) had promoting action on the metabolism process of Carassius aurantus liver mitochondria, but that a high concentration of Na2SeO3 (8-16 mg/L) inhibited the mitochondria metabolism. PMID- 11204469 TI - Bioavailability and possible benefits of wheat intake naturally enriched with selenium and its products. AB - Bioavailability and possible benefits of wheat intake naturally enriched with selenium and its products was tested. Wheat obtained by application of an original combination and procedure for foliar supplementation of plants with Se was characterized on the average by five times higher content of Se, the main form being L-(+)-selenomethionine (SeMet). Substitution of Se-deficient wheat by wheat naturally enriched with Se and its products contributed to the increase of daily intake on the average by 18 microg (12-35 microg) in volunteers, which is more than 50% of the average daily intake. Six weeks after the beginning of its application, increased daily intake of Se brought about the increase of its concentration in the plasma of the examined persons by 53%, in their erythrocytes by 37%, in their hair by 44%, and in their urine by 54%. This result was comparable to the effect obtained in the course of an 8-wk daily intake of supplements with 100 microg Se in the form of enriched bakery yeast. Analysis of glutathione peroxidase (GSH-Px) activity in blood, thiobarbituric acid reactive substances (TBARS) in plasma, lipid parameters (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides), and glucose in serum of volunteers showed that the increased Se intake induced increased GSH-Px activity in blood and decreased concentrations of TBARS, lipid parameters, and glucose in blood. Using only one crop (wheat enriched with Se), the existing deficiency of Se in our population can be alleviated. In this way, one-fourth of our population with lower Se intake than 21 microg/d will satisfy basal requirements, whereas one-half will become moderately deficient in Se instead of distinctly deficient in Se. PMID- 11204470 TI - An external-sample liquid scintillation counting for 75Se and its application to selenoprotein detection. AB - An external-sample liquid scintillation (LS) counting for the gamma emitter 75Se has been developed. An expressly designed well-type LS vial and a 2,5 diphenyoxazole-1,4-bis(5-phenyl-2-oxazoyl)-benzene-xylene solution containing 35% tertrabutylzinn allow 75Se to be counted in a standard LS counter with counting efficiency up to 43.2%, much higher than that of conventional LS counting method. This external sample LS has a good count rate linearity and exhibits low background count rates. After in vivo labeling with [75Se]selenite, 75Se distributions and the Se-containing proteins present in tissues of male rat were investigated by means of sodium dodecyl sulfate-polyacrylamide gel electrophoresis, external-sample LS and gamma-detector. Eight Se-containing proteins or protein subunits were detected to be Se-containing proteins or protein subunits in arterial wall, and their apparent molecular masses (Mr) were 76.4, 67.0, 57.4, 30.3, 25.4, 22.7, 21.7, and 15.1 kDa, respectively. In addition, eight 75Se-labeled proteins (Mr: 66.8, 57.0, 43.1, 30.0, 24.8, 19.8, 18.0, and 14.8 kDa) were found in brain homogenates, and nine 75Se-labeled proteins (Mr: 117.0, 78.0, 66.6, 57.2, 43.0, 38.1, 25.0, 20.1, and 18.0 kDa) were detected in testis homogenates. Some of them should be new biologically important selenoproteins that have not been identified so far. PMID- 11204471 TI - Immune-mediated hemolytic anemia: 70 cases (1988-1996). PMID- 11204472 TI - The use of a Nd:Yag laser for treatment of feline osteoclastic resorptive lesions. PMID- 11204473 TI - Pericardial effusion and pericardiocentesis in a guinea pig (Cavia porcellus). AB - A three-year-old, female guinea pig (Cavia porcellus) presented for acute dyspnea and weakness. Radiographs and echocardiography were consistent with a diagnosis of pericardial effusion and heart failure secondary to cardiac tamponade. Ultrasound-guided pericardiocentesis was performed, and clinical signs rapidly improved. Serial echocardiography and radiographs demonstrated normalization of cardiac function over the subsequent six months. PMID- 11204474 TI - Anatomy of the lumbosacral spinal cord in rabbits. AB - This study provides an accurate, anatomical description of the rabbit's lumbosacral spinal cord. Following humane euthanasia, 64 rabbits were radiographed and dissected. The number of thoracic (T) and lumbar (L) vertebrae was 12T/7L in 43.8%, 13T/6L in 32.8%, and 13T/7L in 23.4% in the 64 rabbits studied. The 13th ribs were rudimentary, asymmetric, or both in 15 animals. The spinal cord terminated within the second sacral vertebra (S2) in 79.3%, within the first sacral vertebra (S1) in 19.0%, and within the third sacral vertebra (S3) in 1.7% of the sample. Spinal nerve contributions to the femoral, obturator, sciatic, and pudendal nerves were determined. Formulas to predict the termination of the cord relative to the vertebral column were established. Age, weight, sex, and method of preparation did not show a significant correlation with the length of the spinal cord. PMID- 11204475 TI - Chylous abdominal effusion in a cat with feline infectious peritonitis. AB - A 10-year-old cat was diagnosed with chyloperitoneum based on the effusion characteristics. Feline coronavirus serology was positive. The owner declined further evaluation and elected euthanasia. Necropsy revealed vasculitis with multifocal areas of necrosis and lymphocytic-plasmacytic inflammation in multiple solid organs, most likely due to feline infectious peritonitis (FIP). Immunohistochemistry was negative for FIP antigen. Notwithstanding, the final diagnosis of FIP was based on the characteristic histopathological lesions. Underlying causes of chyloperitoneum in cats and humans are discussed, and possible pathogenesis of the chyloperitoneum in association with a vasculitis such as FIP is discussed. PMID- 11204476 TI - Canine Rocky Mountain Spotted fever: a retrospective study of 30 cases. AB - Rocky Mountain spotted fever (RMSF) was diagnosed in 30 dogs examined at North Carolina State University, Veterinary Teaching Hospital between 1984 and 1997. Historical, physical examination, and laboratory abnormalities were reviewed. Diagnostic criteria included a four-fold rise in antibody titer to Rickettsia rickettsii (R. rickettsii) (n=15) or a single R. rickettsii antibody titer of 1:1,024 or greater (n=15; when this initial titer was determined one week or more after the onset of clinical signs). Fifteen (50%) dogs were greater than seven years of age, and 13 (43%) dogs were between two and seven years of age. There was no sex predilection. Only five (17%) dogs had a history of known tick exposure. Presumably due to delayed diagnosis, dogs with antibody titers of 1:1,024 or greater at the time of presentation had a higher incidence of more severe neurological dysfunction (e.g., ataxia, hyperesthesia, vestibular disease, and seizures) and cutaneous lesions (e.g., hyperemia, edema, petechiae, ecchymoses, and necrosis). Laboratory findings included anemia, leukocytosis accompanied by toxic granulation of neutrophils, hypoalbuminemia, and coagulation abnormalities; signs were generally more severe in the 15 dogs with R. rickettsii antibody titers of 1:1,024 or greater at the time of presentation. Twelve (40%) dogs in this study were severely thrombocytopenic (less than 75 x10(3) platelets/microl; reference range, 200 to 450 x 10(3)/microl), without clinical evidence of fulminant disseminated intravascular coagulation. In this study, the survival rate following R. rickettsii infection was 100%. PMID- 11204477 TI - Pancreatitis in a cat demonstrating pancreatic duct dilatation ultrasonographically. AB - A 17-year-old, castrated male domestic shorthair cat presented with nonspecific clinical findings of three days' duration. Complete blood counts and serum biochemistry profiles revealed evidence of hepatic dysfunction. Ultrasonographic evaluation revealed abnormalities consistent with pancreatitis, with suspected pancreatic duct dilatation in the left limb of the pancreas. Surgery and eventual necropsy confirmed a diagnosis of pancreatitis, along with pancreatic duct dilatation. Dilatation of the pancreatic duct may be another ultrasonographic change to look for when suspecting feline pancreatitis. PMID- 11204478 TI - Electrocardiographic findings in dogs with motor vehicle-related trauma. AB - Motor vehicle-related injury is the most common form of trauma incurred by dogs, and cardiac arrhythmias are a well-recognized complication. Although posttraumatic arrhythmias are often observed, little is known regarding their frequency. This study utilized continuous ambulatory electrocardiography (i.e., Holter monitoring) to describe the cardiac rhythm disturbances in 30 dogs sustaining trauma in motor vehicle accidents. Ventricular ectopy was identified by Holter monitoring in 29 of 30 dogs, although the initial electrocardiogram (EKG) only documented ventricular ectopic complexes (VECs) in four dogs. Ventricular ectopy was infrequent in most dogs (i.e., 62% of the dogs had less than 100 VECs per day for the entire study), but 16% developed frequent arrhythmias (greater than 4,000 VECs per day). In all cases, the VECs were observed within 24 hours of injury. Forty-three percent of dogs had at least one episode of ventricular tachycardia, including several dogs that had an overall infrequent rate of VECs (i.e., less than 100 or 100 to 1,000 VECs per day). Although baseline EKGs are useful in identifying arrhythmias in most dogs, the length of the recording should be increased to improve the likelihood of observing an abnormal EKG event. Most importantly, additional EKGs should be obtained or continuous EKG monitoring should be performed in dogs that display clinical signs that could be attributed to ventricular arrhythmias. PMID- 11204479 TI - Possible causal association of idiopathic inflammatory bowel disease with thrombocytopenia in the dog. AB - Extraintestinal manifestations of inflammatory bowel disease (IBD) are commonly observed in humans but are poorly documented in companion animals. Thrombocytopenia is an uncommon but well-documented extraintestinal hematological abnormality in humans; however, there are no previous reports of IBD and concurrent thrombocytopenia in the veterinary literature. Seven dogs having idiopathic IBD and concurrent thrombocytopenia were identified and evaluated retrospectively (this represents an incidence of 2.5% in the authors' IBD population). Obvious known causes for thrombocytopenia were eliminated by diagnostic testing as deemed appropriate by the clinician of record. Thrombocytopenia resolved with treatment for the IBD in some but not all patients. This is similar to reports in humans. Thrombocytopenia typically appears to be subclinical, and the severity does not correlate with the degree of intestinal inflammation defined histopathologically. However, quantitative platelet counts should be monitored during IBD therapy, as additional immunosuppression may be required to treat thrombocytopenia, despite resolution of gastrointestinal signs. It is speculated that thrombocytopenia may be causally associated with canine IBD, possibly secondary to immune stimulation from lumenal bacterial antigens, altered immunological regulation, or both. PMID- 11204480 TI - Arthroscopic removal and curettage of osteochondrosis lesions on the lateral and medial trochlear ridges of the talus in two dogs. AB - Osteochondrosis lesions in the tibiotarsal joint were treated arthroscopically in two dogs. One dog had unilateral osteochondrosis of the dorsal aspect of the lateral trochlear ridge of the talus. The second dog had bilateral osteochondrosis of the plantar aspect of the medial trochlear ridge of the talus. Removal of all osteochondral fragments (i.e., joint mice) and debridement and curettage of the remaining talar defects were accomplished arthroscopically. Both dogs had excellent short-term outcomes. PMID- 11204481 TI - Chylothorax in a dog with pulmonary lymphangiosarcoma. AB - Lymphangiosarcoma of the pulmonary pleura was found to be the cause of persistent chylothorax in an eight-year-old, intact male golden retriever. After a two-month course of medical management, a lymphangiogram and thoracic duct ligation were performed with the objective of decreasing further effusion. At surgery, gross lung pathology was biopsied and yielded a histopathological diagnosis of pulmonary pleural lymphangiosarcoma. A relatively rare tumor, lymphangiosarcoma of the pulmonary pleura has not previously been documented as a source of chylothorax in the dog. PMID- 11204482 TI - Surgical treatment of septic peritonitis without abdominal drainage in 28 dogs. AB - The purpose of this study was to evaluate the surgical outcomes of 28 dogs with generalized septic peritonitis treated without postoperative abdominal drainage. The overall mortality rate was 46%, with most cases of peritonitis being caused by leakage of the gastrointestinal tract (75%). Etiology of peritonitis, abdominal cytopathology, total white blood cell count, packed cell volume, total protein, and results of serum biochemistries were not statistically different between survivors and nonsurvivors. The mortality rate of 46% is similar to other studies in which the abdomen was left open postoperatively for the management of septic peritonitis, although more advanced medical treatment than that used in earlier studies may have positively affected the outcome. The results of this study show that closure of the abdomen after the source of contamination has been successfully corrected, in combination with thorough intraoperative peritoneal lavage and appropriate postoperative medical management, may be an acceptable alternative method for the management of septic peritonitis. PMID- 11204483 TI - Surgical treatment of adrenocortical tumors: 21 cases (1990-1996). AB - Twenty-four adrenocortical tumors were surgically removed from 21 dogs. Histopathological examination confirmed 18 carcinomas and six adenomas. Four dogs died in the perioperative period. Fifteen of the 17 dogs that survived the perioperative period had long-term resolution of their clinical signs. Two dogs with incompletely resected tumors were treated with mitotane to control their clinical signs. Overall median Kaplan-Meier life-table survival for dogs with carcinomas was 778 days (range, one to 1,593 days). Median survival for dogs with adenomas was not reached (range, 11 to 730 days). Histopathological diagnosis, histopathological cellular features, age of the dog, and tumor size were not prognostic of outcome. PMID- 11204484 TI - Historical perspectives: 1966. PMID- 11204485 TI - Hematological and TGF-beta variations after whole-body proton irradiation. AB - The acute effects of proton whole-body irradiation on five bone-marrow-derived cell types and transforming growth factor-beta 1 (TGF-beta 1) were examined and compared to the effects of photons (60Co). C57BL/6 mice were exposed to 3 Gy (0.4 Gy/min) protons at spread-out Bragg peak (SOBP), protons at entry (E), or 60Co and euthanized on days 0.5-17 thereafter. 60Co-irradiated animals had decreased erythrocytes, hemoglobin and hematocrit at 12 hours post-exposure; depression was not noted in proton (SOBP or E)-irradiated groups until day 4. Significantly decreased leukocyte counts were observed at this same time in all irradiated groups, with lymphocyte loss being greater than that of monocytes, and the depression was generally maintained. In contrast, the levels of neutrophils and thrombocytes fluctuated, especially during the first week; significant differences were noted among irradiated groups in neutrophil levels. Plasma TGF beta 1 was elevated on day 7 in the 60Co, but not proton, irradiated mice. Collectively, the data show that dramatic and persistent changes occurred in all irradiated groups. However, few differences in assay results were seen between animals exposed to protons (SOBP or E) or photons, as well as between the groups irradiated with either of the two regions of the proton Bragg curve. PMID- 11204487 TI - Immunohistochemical studies on tenascin in extrahepatic bile duct remnants of biliary atresia. AB - The expression of tenascin in the extrahepatic bile duct remnants in biliary atresia was investigated using an immunohistochemical method. Tenascin is thought to be a marker of repair of injured tissues based on an immunohistochemical study of a variety of tissues. Twenty-three specimens were obtained from 23 cases (2 correctable type and 21 non-correctable type) of biliary atresia at the time of the definitive operation. Positive tenascin staining was observed in matrices surrounding degenerated epithelium of the bile ductules in the obliterated extrahepatic bile duct. Regarding the correlation between the size of the bile ductule and the degree of positive staining, the larger diameter bile ductules tended to show a higher degree of positive staining. Furthermore, regarding the correlation between the degeneration of epithelium and the degree of staining, the bile ductules with the more significantly denuded epithelium tended to show a higher degree of positive staining. In some specimens classified as non correctable type, a lumen larger than 1 millimeter in diameter without epithelium was observed. This ductule itself was thought to be the original extrahepatic bile duct because strong tenascin staining was observed surrounding this lumen. These findings suggested that the extrahepatic bile duct might be obliterated after the completion of the hepatobiliary tree system and the bile ductules in the obliterated extrahepatic bile duct might be degenerated in order of their size. PMID- 11204486 TI - Acute pancreatitis associated with administration of a nitric oxide synthase inhibitor in tumor-bearing dogs. AB - BACKGROUND: Nitric oxide synthase (NOS) inhibitors have been investigated as potential cytotoxic agents to treat tumors lacking p53 function. Furthermore, their ability to reduce tumor blood flow can be combined with drugs that are specifically designed to kill cells that are hypoxic or to improve temperatures during local heat (hyperthermia) treatment of tumors. This paper reports the unexpected development of acute pancreatitis in two tumor-bearing pet dogs that were treated with the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) during administration of local hyperthermia. METHODS: Prior to the use of L-NAME in tumor-bearing dogs, purpose-bred beagles were studied. Following induction of inhalation anesthesia, local hyperthermia was applied to either normal thigh muscle (beagles) or tumors (tumor-bearing dogs). Once a thermal steady state was achieved, L-NAME was administered and temperature monitoring continued. Animals were observed after treatment for evidence of toxicity. RESULTS: The beagles tolerated the treatment well, with no side effects noted either clinically or by routine CBC or blood chemistry analyses. In contrast, the first two tumor-bearing dogs accrued onto the phase I study developed acute pancreatitis in the immediate post-treatment period which necessitated hospitalization and intensive care. The trial was stopped. Both dogs had intercurrent risk factors which predisposed them to development of pancreatitis, although neither had a history of symptoms of pancreatitis at the time the hyperthermia + L-NAME treatment was given. CONCLUSIONS: We conclude that caution should be exercised when considering NOS inhibition for cancer treatment. Careful evaluation of history and health status as well as recognition of potential risk factors may be key in avoiding potentially fatal complications. This study demonstrates the value of performing potentially harmful treatments in tumor-bearing dogs prior to introduction into the human clinic. PMID- 11204488 TI - Oxidative stress of red blood cells during Bacillus Calmette-Guerin intravesical instillations. AB - Although Bacillus Calmette-Guerin (BCG) intravesical instillation is widely accepted as a very effective modality in treating bladder carcinoma in situ, and in preventing superficial bladder cancer recurrence, its mechanism of action is not yet fully understood. The antitumor effects of BCG are mostly related to local immunological events but a systemic activation of the immune system cannot be excluded. The objective of the present study was to estimate the systemic production of oxidants during intravesical BCG treatment. Systemic production of oxidants was estimated by assessing the red blood cells (RBC) oxidative stress in twelve patients undergoing BCG immunotherapy for bladder carcinoma in situ. RBC oxidative stress induced by peroxynitrite was determined by luminol-enhanced chemiluminescence. During the treatment period, the RBC oxidative stress revealed a biphasic curve of changes: after an initial 5-fold increase, it dropped to pretreatment levels following the 4th instillation. Intravesical BCG administration induced systemic production of oxygen free radicals that may reflect a systemic activation of the immune system. PMID- 11204489 TI - Oncogene activation and tumor suppressor gene inactivation find their sites of expression in the changes in time and space of the age-adjusted cancer incidence rate. AB - The purpose of the present investigation is to elucidate the relation between the distribution pattern of the age-adjusted incidence rate (AAIR) changes in time and space of 15 tumors of bothe sexes and the locations of centers of centripetal (oncogene type) and centrifugal-(tumoe suppressor gene type) forces. The fitness of the observed log AAIR data sets to the oncogene type- and the tumor suppressor gene type-equilibrium models and the locations of 2 force centers were calculated by applying the least square method of Gauss to log AAIR pair data series with and without topological data manipulations, which are so designed as to let log AAIR pair data series fit to 2 variant (x, y) frameworks, the Rect-coordinates and the Para-coordinates. The 2 variant (x, y) coordinates are defined each as an (x, y) framework with its X axis crossed at a right angle to the regression line of the original log AAIR data (the Rect-coordinates) and as another framework with its X axis run in parallel with the regression line of the original log AAIR pair data series (the Para-coordinates). The fitness test of log AAIR data series to either the oncogene activation type equilibrium model (r = -1.000) or the tumor suppressor gene inactivation type (r = 1.000) was conducted for each of the male-female type pair data and the female-male type data, for each of log AAIR changes in space and log AAIR changes in time, and for each of the 3 (x, y) frameworks in a given neoplasia of both sexes. The results obtained are given as follows: 1) The positivity rates of the fitness test to the oncogene type equilibrium model and the tumor suppressor gene type model were each 63.3% and 56.7% with the log AAIR changes in space, and 73.3% and 73.3% with log AAIR changes in time, as tested in 15 human neoplasias of both sexes. 2) Evidence was presented to indicate that the clearance of oncogene activation and tumor suppressor gene inactivation is the sine qua non premise of carciniogenesis. 3) The r profile in which the correlation coefficient r, a measure of fitness to the 2 equilibrium models, is converted to either +(r > 0) or -(0 > r) for each of the original-, the Rect-, and the Para-coordinates was found to be informative in identifying a group of tumors with sex discrimination of cancer risk (log AAIR changes in space) or another group of environmental hormone-linked tumors (log AAIR changes in time and space)--a finding to indicate that the r-profile of a given tumor, when compared with other neoplasias, may provide a clue to investigating the biological behavior of the tumor. 4) The recent risk increase of skin cancer of both sexes, being classified as an example of environmental hormone-linked neoplasias, was found to commit its ascension of cancer risk along the direction of the centrifugal forces of the time- and space-linked tumor suppressor gene inactivation plotted in the 2-dimension diagram. In conclusion, the centripetal force of oncogene activation and centrifugal force of tumor suppressor gene inactivation found their sites of expression in the distribution pattern of a cancer risk parameter, log AAIR, of a given neoplasias of both sexes on the 2-dimension diagram. The application of the least square method of Gauss to the log AAIR changes in time and space, and also with and without topological modulations of the original sets, when presented in terms of the r-profile, was found to be informative in understanding behavioral characteristics of human neoplaisias. PMID- 11204490 TI - Development of a saliva sampling method and a rocket immunoelectrophoretic assay for quantification of salivary IgA in the squirrel monkey (Saimiri sciureus). AB - There has long been the requirement for a marker of well being and chronic stress that is, itself, unaffected by the transient stressors associated with sampling. Work done in the human, the rat and the dog suggests that salivary IgA may fulfil these criteria. This is the first report on the establishment of a saliva sampling technique and immunoelectrophoretic assay for quantification of secretory Immunoglobulin A (s-IgA) in the squirrel monkey (Saimiri sciureus). A safe and effective sampling method is described, as well as a detailed description of an accurate rocket immunoelectrophoretic assay developed for this study. Preliminary results demonstrate a large intra-individual variation, as well as inter-individual variation in s-IgA levels between successive days. This indicates that if stress is associated with decreased s-IgA levels in the squirrel monkey, the usefulness of s-IgA as a stress marker may be limited because analyses of large numbers of samples may be necessary in order to obtain significance. PMID- 11204491 TI - Blood levels of ruthenium following repeated treatments with the antimetastatic compound NAMI-A in healthy beagle dogs. AB - NAMI-A is a new generation ruthenium compound which is entering phase-I clinical trials anti-metastatic agent. This study analyses the effects of the i.v. injection of NAMI-A to healthy Beagle dogs at increasing doses from 0.4 (low) 4 (mid) and 8 (high) mg/kg/day, given for 5 consecutive days. Only mild signs of toxicity, consisting of emesis and mucoid faeces, from which animals completely recovered, occurred during treatment at the high dose. Decay of ruthenium concentration from the whole blood, 24 hr after 5-days treatment, was lower than that observed after 1-day treatment. T1/2 was about 20-23 hr, or slightly longer when the animals were hydrated with tap water prior to treatment; Cltot was 21-22 ml*hr-1, decreasing to 13 ml*hr-1 after hydration and increasing to 34 ml*hr-1 with the high dose. AUC was proportional to the dose used. Thus NAMI-A is well tolerated by healthy dogs with blood levels comparable to those obtained in mice treated with an about 10-times higher daily dose. PMID- 11204492 TI - Subtyping of cytomegalovirus strains obtained from immunocompetent children. AB - We analyzed 33 clinical isolates of cytomegalovirus (CMV) obtained from immunocompetent Japanese children. DNA was extracted from infected MRC-5 cells and we amplified CMV glycoprotein-B (gB), major IE (MIE), DNA polymerase and glycoprotein-H (gH) genes using PCR. Among the 33 clinical isolates, 24 were identified as gB group 1, one as group 2, 6 as group 3, and 2 as simultaneous infections with group 1 and group 3 strains. Clinical isolates of CMV have also been classified into 18 MIE, 8 DNA polymerase and 15 gH genotype patterns by restriction fragment length polymorphism (RFLP). RFLP analysis is useful in molecular epidemiological studies of CMV infection in immunocompetent individuals. PMID- 11204493 TI - The effect of humoral immunity against adducted benzo[a]pyrene on DNA damage elicited by acute carcinogen exposure in Swiss mice. AB - Immunoglobulins G (lgG) specific for benzo[a]pyrene-DNA adducts were elicited in Swiss mice by repeated subcutaneous injections of a high molecular weight benzo[a]pyrene-DNA conjugate-adjuvant mix. The immunization procedure resulted in the production of specific antibodies against adducted benzo[a]pyrene B[a]P in all treated animals. One week after completion of the immunization procedure, groups of ten immunized and ten non immunized female mice were treated by single intraperitoneal injection with two different doses of B[a]P. The mice were sacrificed 48 hours after treatment, and both liver and bone marrow cells were isolated for subsequent determinations of DNA binding and micronucleus induction, respectively. Covalent benzo[a]pyrene adducts in liver DNA were detected by competitive ELISA and the incidence of micronucleated polychromatic erythrocytes was evaluated by scoring one thousand cells per animal. The determination of DNA adducts in liver revealed significantly (p < 0.05) lower levels of B[a]P adducts in immunized mice compared to non-immunized animals at both doses, whereas no significant difference was observed between controls. Administration of benzo[a]pyrene produced moderate, dose-related increases in the incidence of micronucleated polychromatic erythrocytes in all treated groups, with no significant difference between immunized and non-immunized mice. The decrease of covalent DNA adducts in the liver of immunized mice suggests that the specific humoral immunity elicited by repeated carcinogen exposure may act as a relevant modulating factor in chemical carcinogenesis. PMID- 11204494 TI - Divergent synergic effects in carcinogenesis initiation by simultaneous exposure to two genotoxic carcinogens. AB - Carcinogenesis is a complex and multistep process starting from initiation to tumor progression. Synergistic mechanisms can occur at every step of the process. The aim of this work was to provide information about the effect of chemical carcinogens which, if administered in combination, result in positive as well as negative synergistic effects. In order to evaluate whether for some carcinogens synergism occurs at the initiation step, we compared the effects of Ethylmethanesulfonate (EMS) on Benzo[a]pyrene (BP)-DNA adducts formation in the liver and lung of male Swiss mice treated for seven days by i.p. dose of EMS (1.2 mg/Kg b.w.) alone or by simultaneous administration of three doses of BP (25, 50, 100 mg/Kg b.w.) injected i.p. or the first day of treatment. A group of Swiss mice was treated by BP alone. At it was demonstrated in our laboratory that previous immunization toward BP influences the adduct levels of this carcinogen (14), the same treatments (BaP alone and BaP with EMS) were carried out in mice previously immunized toward BP. Liver and lung 1 BP-DNA adducts were detected in all the groups treated by both BP and EMS as compared to the group treated with BP alone. The EMS-BP association in non-immunized mice showed an antagonistic effect in the liver and a synergistic effect in the lung. In immunized mice a synergistic effect was obtained in both liver and lung. Moreover, the efficiency of both the synergistic and antagonistic effect, depended on BP dose of treatment. It is reasonable to draw the conclusion that simultaneous exposure to BP and EMS leads to different organ-specific and dose-dependent effects. This first preliminary result showed that the pattern of the interaction between genotoxic carcinogens is more complex that was foreseen, even at the stage of DNA adducts formation. PMID- 11204495 TI - Radiation induced early nuclear changes in cytologic brush specimens from the upper aerodigestive tract. AB - OBJECTIVE: To evaluate the feasibility of DNA image cytometry to assess radiation induced early nuclear changes in cytologic smears from the upper aerodigestive tract. METHODS: 100 cytologic brush specimens from 50 postoperatively irradiated patients with upper aerodigestive tract carcinoma were examined Smears were taken from clinically inconspicuous mucosa from the former tumor site and from a control region (contralateral side). Cellular DNA was quantified using the CAS 200 image analysis system on Feulgen stained slides. DNA histograms were evaluated using the coefficient of variation (CV), the DNA index (DI), the 2c deviation index (2cDI) and the 2.5c exceeding rate (2.5cER). RESULTS: All specimens from the control region were diploid. Forty-six smears from the former tumor region were diploid and in four cases non-diploid cells were found. Single cells with a DNA content exceeding 5c ('5c exceeding events'), were identified in three non-diploid and six diploid smears from the former tumor region. CONCLUSION: DNA analysis is a useful tool in detecting early nuclear changes preceding morphologic changes. PMID- 11204496 TI - Experimental inoculation of laboratory animals with samples collected from sarcoidal patients and molecular diagnostic evaluation of the results. AB - Studies on the implication of mycobacteria in the pathogenesis of sarcoidosis have generated conflicting results. In an attempt to further elucidate the etiology of the disease, we obtained broncho-alveolar lavage (BAL) samples from sarcoidal patients, which were subsequently used for intra-tracheal inoculation of a group of rabbits. Patients were characterized as sarcoidal on the grounds of clinical, radiographic, histological and microbiological testing. Four months following inoculation, lung and alveolar lymph node specimens were collected from the animals and were examined by means of histology and microbiology, as well as by a polymerase chain reaction (PCR) assay, targeted to DNA sequences of the Mycobacterium tuberculosis and Mycobacterium avium complexes. All of the twenty five BAL-inoculated rabbits revealed evidence of lobar pneumonia, with thirteen developing lesions of non-caseous granulomatous inflammation, similar to those observed in sarcoidal patients. Microbiological cultivation of lung and alveolar lymph node material, Zihl-Neelsen staining of corresponding tissue sections and PCR analysis of extracted DNA yielded no evidence of mycobacterial infection. Identical processing of biopsies originating from the martyrs, formerly inoculated with drinking water or disinfected BAL, revealed no pathological signs. Our findings suggest that BAL samples from patients with sarcoidosis may carry an agent that produces a disease characterized by similar histological lesions in rabbits. However, culture, and PCR, could not identify this agent as a member of Mycobacterium tuberculosis, or Mycobacterium avium complexes. PMID- 11204497 TI - Dietary administration of tannic acid lowers plasminogen activator activity in the liver of C3H hepatoma bearing male mice. AB - BACKGROUND: This study was undertaken to investigate if low-dose dietary administration of tannic acid exerts its chemopreventive activity on hepatocarcinogenesis in male C3H mice through changes of plasminogen activator activity (PAA), plasminogen activator inhibition (PAI) or plasmin inhibition (Pl) in the liver of C3H hepatoma bearing male mice. MATERIALS AND METHODS: Tannic acid was administered in the drinking water of hepatoma bearing C3H mice, in a concentration of 0.0075% (group B), 0.015% (group C) and 0.03% (group D) for 9 months. PAA, PAI and PI were measured by spectrophotometric methods in macroscopically healthy liver regions. RESULTS: Tannic acid induced a decrease of PAA (53%) and an increase of PAIs (50%) in the livers of group D while tannic acid received mice showed a dramatic decrease in liver carcinomas incidence (0% vs 33.3% in the control group). CONCLUSION: The decrease of PAA in the liver of C3H hepatoma bearing male mice, might be correlated with the chemopreventive activity of tannic acid in hepatoma development. PMID- 11204498 TI - The role of apoptosis in normal ontogenesis and solid human neoplasms. AB - Mammalian cells are capable of committing "active suicide" or apoptosis in response to specialized pathological mechanisms employing a phylogenetically developed intrinsic program of death, triggered by signal transduction through specific receptors. Changes in cellular structure such as: 1) condensation of the nuclear (chromatin) and cytoplasmic structures (especially the mitochondria); 2) blebbing of the cell membrane; 3) characteristic swelling of the endoplasmic reticulum; and 4) fragmentation of the cells in membrane bound apoptotic bodies, are the dramatic signs of total cell destruction. Apoptosis requires energy in the from of ATP, indicating that programmed cell death (PCD), as opposed to necrosis, is an energy dependent, active physiological and pathophysiological phenomenon. During this immunocytochemical study, we observed the presence of PCD in the prenatal thymus and various human neoplastically transformed tissues. During the intrauterine ontogenesis, in thymocytes or resting T lymphocytes, p53 tumor suppressor protein was identified to be a critical mediator of PCD in response to DNA damage. The cellular interaction of immature, cortical thymocytes (characterized by a double positive CD4+CD8+TCRlow immunophenotype-IP) with thymic RE cells induces positive selection of T lymphocytes that recognize, but are not activated, by self-MHC molecules (tolerance induction). Double positive CD4+CD8+CD3- thymocytes undergo FasL-mediated apoptosis, while CD4+CD8+CD3+ cells use the CD3 mediated pathway of PCD. Two step, apoptotic cell death is mainly restricted to the CD4+CD8+TCR dull thymocyte subpopulation. T-lymphocytes which do not undergo positive selection are killed by apoptosis in response to a number of intrinsic and extrinsic factors, such as chemical toxins, viral infections, X- and UV irradiation, mild hyperthermia, the actions of various hormones, extracellular survival factors, calcium ionophores (such as A23187), various chemotherapeutic drugs (adriamycin, actinomycin D, etc) and antibodies directed to the CD3-TCR (T cell receptor) complex. Immature thymocytes also undergo a second selective process, so-called negative selection, when thymic stromal cells eliminate autoreactive T lymphocytes. As a typical model of embryonal neoplasms, we observed 34 childhood PNET/MED tissues samples. A systematic observation for the presence of apoptosis related markers (especially FasR) and cells in PCD was carried out. A strong expression (intensity of staining: "A"--the highest possible; number of stained neoplastic cells: +++ to ++++, between 50% to 90%) of FasR was detected. We also observed 42 childhood glial tumors, divided as follows: 6 pilocytic ASTRs; 14 low grade ASTRs; 16 anaplastic ASTRs; and 6 GBMs. The GBMs represent an end-stage brain tumor IP dedifferentiation of glial origin. During the immunocytochemical screening of these 42 childhood ASTRs, we detected strong expression (intensity of staining: "A"--the highest possible; number of stained cells: ++ to ++++, between 20% to 90%) of FasR, employing 4 microns thick, formalin fixed, paraffin-wax embedded tissue slides. FasR expression was rated high, 70% to 90% on the tumor cells in pylocytic ASTRs, lowered to 50% to 60% on the neoplastic cells in low grade ASTRs, even lower between 30% to 40% in anaplastic ASTRs and significantly lower, between 20% to 35% on the neoplastically transformed cells of GBM tissues. The presence of apoptotic neoplastic cells was also regularly detected in other human adult neoplasms, such as thyroid, pancreatic, hepatocellular, gastric, colon, breast, ovarian, prostata, and renal cell carcinomas, as well as, in Hodgkin and non-Hodgkin lymphomas and some sarcomas. The expression of apoptosis related cell surface molecules on the surface of both neoplastically transformed cells and on tumor cell specific, cytotoxic T lymphocyte (CTL) surfaces (FasR-FasL system) raises a distinct possibility of active PCD induction in CTL by tumor cells. Juxtacrine interactions between CTL and neoplastically transformed cells, coupled with observations that tumor cells can modulate the intracellular, signaling domains of cell surface receptors to elicit responses quite often contrary to the expected, may even provide a way for CTL to enhance the proliferation and dedifferentiation of cancer cells. Adoptive cellular immunotherapies employing CTL raised against autologous neoplastically transformed cells in vitro should be employed in the control of minimal residual disease following surgical resection of the primary malignant growth. PMID- 11204499 TI - Hepatitis C virus infection mimicking primary Sjogren syndrome. A clinical and immunologic description of 35 cases. AB - Hepatitis C virus (HCV) infection is emerging as an extremely common and insidiously progressive liver disease that is often associated with several extrahepatic manifestations. In 1992, a possible relationship between Sjogren syndrome (SS) and patients with HCV infection was first postulated. Subsequently, several studies demonstrated that a "true" SS, with similar clinical and histologic features to those observed in primary SS, may occur in some patients with chronic HCV infection. We report the clinical and immunologic characteristics of 35 patients with chronic HCV infection and a well-documented diagnosis of SS. Compared with 60 patients with primary SS who tested negative for HCV antibodies, SS-HCV patients showed a higher mean age (65.9 yr versus 61.5 yr, p = 0.04), a lower prevalence of parotidomegaly (17% versus 47%, p = 0.004), and a higher prevalence of liver involvement (94% versus 3%, p < 0.001). Moreover, those patients with HCV-related SS showed a higher prevalence of anti parietal cell gastric antibodies (31% versus 13%, p = 0.03), antimitochondrial antibodies (14% versus 2%, p = 0.02), cryoglobulinemia (60% versus 10%, p < 0.001), hypocomplementemia (60% versus 8%, p < 0.001), and a lower prevalence of anti-Ro/SS-A (17% versus 38%, p = 0.03). The "true" SS observed in some patients with HCV may be considered 1 of the extrahepatic manifestations of HCV, and we suggest that HCV infection can be considered as an exclusion criterion for the diagnosis of primary SS. PMID- 11204500 TI - Physiology and pharmacology of iodized oil in goiter prophylaxis. AB - Thyroid complications resulting from excess iodide such as thyrotoxicosis, thyroiditis, sialadenitis, or hypothyroidism are much rarer after iodine supplementation with Lipiodol than with KI. They do not militate against its widespread use in endemic goiter populations, especially in pregnant women. However, patients with multinodular goiter should not be treated or should be treated only under careful observation. When Lipiodol-induced thyrotoxicosis occurs it tends to be mild or even subclinical and self-limited. If treatment is required, potassium perchlorate with or without thionamides is recommended. Iodide goiter has not been seen after Lipiodol supplementation, nor has thyroiditis. Sialadenitis occurs rarely. Iodide derived from Lipiodol readily enters the fetus, possibly by active transport, and theoretically endangers the fetus because autoregulation of the fetal thyroid occurs late during gestation. Despite the difficulty in distinguishing iodide goiter from iodide deficiency goiter of the newborn, no cases of neonatal iodide goiter have been reported. Possible mechanisms of thyroid inhibition by excess iodide are briefly discussed. The use of locally produced iodized plant oils is recommended for financial reasons as well as for the benefits derived from local participation. PMID- 11204501 TI - The Schnitzler syndrome. Four new cases and review of the literature. AB - The Schnitzler syndrome is characterized by a chronic urticarial eruption with a monoclonal IgM gammopathy. The other signs of the syndrome include intermittent elevated fever, joint and/or bone pain with radiologic evidence of osteosclerosis, palpable lymph nodes, enlarged liver and/or spleen, elevated erythrocyte sedimentation rate, and leukocytosis. The mean delay to diagnosis is more than 5 years, and this syndrome is of concern to internists and many medical specialists. Patients with this syndrome are often initially considered to have lymphoma or adult-onset Still disease, which are the main differential diagnoses. However, hypocomplementic urticarial vasculitis, systemic lupus erythematosus, cryoglobulinemia, acquired C1 inhibitor deficiency, hyper IgD syndrome, chronic infantile neurologic cutaneous and articular (CINCA) syndrome, and Muckle-Wells syndrome should also be excluded, because diagnosis relies on a combination of clinical and biologic signs and there is no specific marker of the disease. The disease pursues a chronic course, and no remissions have yet been reported. Disabling skin rash, fever, and musculoskeletal involvement are the most frequent complications. Severe anemia of chronic disease is another serious complication. The most harmful complication, however, is evolution to an authentic lymphoplasmacytic malignancy, which occurs in at least 15% of patients. This hematologic transformation can occur more than 20 years after the first signs of the disease, thus patients deserve long-term follow-up. Treatment is symptomatic and unsatisfactory. The skin rash is unresponsive to treatment, and nonsteroidal antiinflammatory drugs, antihistamines, dapsone, colchicine, and psoralens and ultraviolet A (PUVA) therapy give inconstant results. Fever, arthralgia, and bone pain often respond to nonsteroidal antiinflammatory drugs. In some patients, these symptoms and/or the presence of severe inflammatory anemia require steroids and/or immunosuppressive treatment, which ameliorate inflammatory symptoms but do not change the course of the skin rash. PMID- 11204502 TI - Bilateral massive adrenal hemorrhage. Assessment of putative risk factors by the case-control method. AB - Case reports and case series have identified putative risk factors for the development of bilateral massive adrenal hemorrhage (BMAH) in humans. The anatomy and physiology of the adrenal gland allow development of a model to fit the pathophysiology behind these risk factors. Until now, these risk factors were not systematically tested using analytical epidemiologic studies. A case-control study was undertaken using sources of cases and controls from multiple teaching hospitals in Ontario, Canada. The results of multivariate logistic regression indicated that thrombocytopenia (odds ratio [OR] = 14.6, 95% confidence intervals [CI] = 3.0-70.1, p < 0.001), heparin exposure of any route or type beyond 3 days (4-6 days: OR = 17.0, CI = 1.9-154.6; > 6 days: OR = 33.5, CI = 4.3-262.6; p < 0.001), and sepsis (OR = 6.3, CI = 1.2-32.2, p = 0.019) were most strongly and independently associated with development of BMAH. Another weaker positive association included invasive radiologic procedure (OR = 4.4, CI = 0.9-22.1, p = 0.055). Neither major surgery or duration of hospitalization were independent risk factors. Although coronary artery disease and possibly diabetes and hypertension appeared to be markers for lower risk of BMAH, this may be a result of bias introduced by using hospital controls ("Berkson bias"), as the effect was not explained by a protective effect of vasoactive medications. Thus, a picture of the high-risk patient should include a patient who has been treated with heparin (any route or type) beyond 3 days and has had thrombocytopenia (not necessarily induced by heparin) during the course of an illness. If the setting includes unexplained abdominal, chest, or back pain; fever; confusion; hypotension or shock; abrupt anemia; or electrolyte disorders, clinicians should not hesitate to cover empirically with lifesaving glucocorticoids while awaiting results of confirmatory tests. PMID- 11204503 TI - Visceral leishmaniasis in human immunodeficiency virus (HIV)-infected and non-HIV infected patients. A comparative study. AB - Visceral leishmaniasis is an endemic infection in Mediterranean countries, where it has become a frequent complication of acquired immunodeficiency syndrome (AIDS). The incidence of visceral leishmaniasis is increasing in Spain due to human immunodeficiency virus (HIV)-related cases, but some aspects of its epidemiology, clinical features, and management remain unknown. In addition, no comparative clinical studies about the disease in HIV-infected and non-HIV infected patients have been reported. During a 24-year period, 120 cases of visceral leishmaniasis were diagnosed at our institution and 80 (66%) were associated with HIV infection. The mean age at diagnosis was higher in HIV infected that in non-HIV-infected patients (33.2 versus 23.2 yr; p = 0.002), but the male/female ratio was similar in both groups. The main risk factor for HIV infection was intravenous drug abuse (78.7%). The clinical presentation of leishmaniasis was similar in both groups, but HIV-infected patients had a lower frequency of splenomegaly than HIV-negative individuals (80.8% versus 97.4%; p = 0.02). HIV-infected patients had a greater frequency and degree of leukopenia, lymphocytopenia, and thrombocytopenia. Most of them were profoundly immunosuppressed (mean CD4+ lymphocyte count, 90 cells/mm3) at the time of diagnosis of leishmaniasis, and 53.7% had AIDS. The sensitivity of serologic studies for Leishmania was significantly lower in HIV-infected than in non-HIV infected patients (50% versus 80%; p < 0.001), but the diagnostic yield of bone marrow aspirate (67.1% versus 79.4%) and bone marrow culture (62.9% versus 66.6%) was similar in both groups. After initial treatment, the response rate was significantly lower in HIV-infected than in non-HIV-infected individuals (54.8% versus 89.7%; p = 0.001). The relapse rate was 46.2% and 7.5%, respectively (p < 0.001). Secondary prophylaxis with antimonial compounds or amphotericin B seems to be useful in preventing relapses in HIV-infected patients. The mortality rate was higher (53.7% versus 7.5%; p < 0.001) and the median survival time shorter (25 versus > 160 mo; p < 0.001) in AIDS patients than in HIV-negative individuals. Although leishmaniasis could contribute to death in a significant number of HIV-infected patients, it was the main cause of death in only a few of them. The CD4+ lymphocyte count and the use of highly active antiretroviral therapy and secondary prophylaxis for leishmaniasis were the most significant prognostic factors for survival in AIDS patients. Visceral leishmaniasis behaves as an opportunistic infection in HIV-infected individuals and should be considered as an AIDS-defining disease. PMID- 11204505 TI - Participatory medicine. PMID- 11204504 TI - Rheumatic manifestations of infective endocarditis in non-addicts. A 12-year study. AB - Infective endocarditis (IE) is due to a microbial infection of the heart valves or of the endocardium in close proximity to either congenital or acquired cardiac defects. This infection is associated with a high risk of complications. Rheumatic manifestations are known to be frequent complications of IE. Controversy, however, frequently exists about the actual incidence of these complications. This may be due to the small number of series describing the frequency and type of rheumatic manifestations, the absence of uniform criteria used for the diagnosis of IE, and the fact that some studies on rheumatic manifestations in IE have been described from tertiary referral centers, which implicates associated problems of referral bias and uncertainty of denominator population. To investigate further the incidence, clinical spectrum, and outcome of patients with IE and rheumatic manifestations, we examined the features of patients diagnosed with clinically definite IE according to the Duke classification criteria at the single reference hospital for a defined population in northwestern Spain during a 12-year period. Between 1987 and 1998, 100 consecutive patients had 110 episodes of clinically definite IE. Rheumatic manifestations were observed in 46 of the 110 episodes (41.8%). As in other western countries, they occurred more commonly in men aged in their 50s. The most frequent valve involved was the aortic (43.5%) followed by the mitral valve (30.4%). Myalgia was a frequent symptom. Peripheral arthritis, generally as monoarthritis, was clinically evident in 15 cases (13.6%), and sacroiliitis in 1 patient. Low back pain was described in 14 cases (12.7%). Septic discitis was observed in 2 cases, and biopsy-proved cutaneous leukocytoclastic vasculitis was found in 4 cases. Other conditions such as trochanteric bursitis and polymyalgia were observed in 2 and 1 case, respectively. Apart from a significantly higher frequency of hematuria and a trend to lower serum complement levels in patients with rheumatic complications, no differences in clinical features, laboratory tests, or microbiologic blood culture results were found between cases with IE with or without rheumatic manifestations. Also, although patients with rheumatic manifestations had more embolic complications, the inhospital mortality rate in patients with rheumatic manifestations was not significantly different from that of the rest of the patients. The present study supports the claim that rheumatic complications are frequent in patients with clinically definite IE from southern Europe. The presence of musculoskeletal or vasculitic manifestations may be of some help, as warning signs, for the recognition of patients with severe disease who require rapid diagnosis and therapy. PMID- 11204506 TI - Quality of life of psoriasis patients. PMID- 11204507 TI - Water barrier function: what's new? PMID- 11204508 TI - Topical revitalization of body skin. PMID- 11204509 TI - Chronic radiation dermatitis: what's new in management? PMID- 11204510 TI - Pustulosis palmaris et plantaris. PMID- 11204511 TI - Blastomycosis: what's new? PMID- 11204512 TI - Cellulite: a review. AB - Gynoid lipodystrophy (cellulite) is an extremely controversial topic. A lack of knowledge regarding specific aetiopathogenic factors, as well as the opportunism of some professionals and the media, has fuelled debate regarding the scientific basis of this condition. This article reviews the clinical, epidemiological, histopathological and therapeutic aspects of cellulite. PMID- 11204513 TI - Adhesion molecule profiles in atopic dermatitis vs. allergic contact dermatitis: pharmacological modulation by cetirizine. AB - BACKGROUND: Experimental data suggest that there is an imbalance between Th1 and Th2 cells in atopic dermatitis (AD) skin compared to allergic contact dermatitis (ACD). This imbalance (Th2 and Th1 predominance, respectively) implies the production of different cytokines in these two conditions leading to different expression of adhesion molecules on skin endothelial cells. OBJECTIVE: The expression of VCAM-1 (IL-4/Th2-dependent) and ICAM-1 (INF-gamma/IL-1) on dermal vessels was compared in six patients with AD and six patients with ACD. The effect of cetirizine, a highly selective H1-receptor antagonist on the expressions was studied. METHODS: Six patients with AD were challenged with Dermatophagoides pteronyssimus (DPT patch tests applied to clinically normal skin) and six patients with ACD challenged in the same way with allergens of the European standard series. Skin biopsies at challenged sites were performed before and 6, 24 and 48 h after challenge. The experiment was carried out under double blind cross-over conditions during a 4-day treatment with a placebo and cetirizine. RESULTS: In AD patients, the scores for both VCAM-1 and ICAM-1 were high before and after challenge. In ACD patients, the ICAM-1 score was high at each experimental time, but the VCAM-1 score, which was significantly lower before challenge, increased at 6, 24 and 48 h after challenge. The administration of cetirizine significantly reduced the VCAM-1 expression in AD patients at each experimental time. CONCLUSION: It is concluded that the increased VCAM-1 expression in AD patients compared to ACD may reflect greater IL-4 and/or IL-13 production in situ. The study also confirms the existence of a modulating effect of cetirizine in vivo on adhesion molecule expression. PMID- 11204514 TI - The depression, anxiety, life satisfaction and affective expression levels in psoriasis patients. AB - OBJECTIVE: The aim of this study was to determine the effect of stressful life events on the onset and exacerbation of psoriasis, depression, anxiety, life satisfaction and affective expression levels in psoriasis patients and psychological risk factors related to psoriasis. METHOD: Fifty psoriasis patients were examined dermatologically and psychiatrically and then administered the Beck Depression Inventory (BDI), Spielberger State-Trait Anxiety Scale (STAI I-II), Life Satisfaction Scale (LSS), Courtauld Emotional Control Scale (CECS) and Body Image Satisfaction Scale (BIS). Symptom severity was measured by the Psoriasis Area Severity Index (PASI). RESULTS: Thirty-four patients declared that they had had a psychologically stressful life event in the last 3 months prior to the beginning of the illness. The mean PASI score was 1.75+/-1.65; BDI score 13.58+/ 6.11; STAI-I score 39.54+/-9.18, STAI-II score 46.58+/-8.05; LSS score 9.18+/ 4.39; CECS score 51.64+/-9.75; BIS score 93.74+/-16.67. CONCLUSION: Psoriasis patients reported significantly higher degrees of depression and more body cathexis problems than controls. In addition, the risk for developing psoriasis increased significantly in patients with moderate and severe depression. We also found a relationship between symptom severity and low affective expression and high BDI scores in this study. These findings suggest that the relationship between psoriasis and psychological problems can be reciprocal and requires further investigation. PMID- 11204515 TI - Incorporation of ceramide 3B in dermatocosmetic emulsions: effect on the transepidermal water loss of sodium lauryl sulphate-damaged skin. AB - BACKGROUND: In previous work we reported on the efficacy of cosmetic body lotions enriched with skin-identical lipids to reduce the transepidermal water loss (TEWL) of ageing and sodium lauryl sulphate (SLS)-damaged skin. The observations made depended on the experimental design and clearly raised the question of the importance of the galenic formulation of skin ceramide-containing products. OBJECTIVES: The aim of the present work was to study the different galenic forms in which ceramide 3B (0.2% w/v) can be incorporated into common o/w emulsions. In addition, we investigated whether supplementation of skin care products with ceramide 3B enriched with penetration enhancers and coemulsifiers could exert a beneficial effect on barrier function, done by measuring their effects on the TEWL of SLS-induced scaly skin. RESULTS: We found that the technique of incorporating ceramide 3B into the o/w emulsions was important for their final stability. However, no additional positive effect on the TEWL values of SLS damaged skin could be observed when the efficacy of the ceramide-containing emulsions was compared with that of proper controls. CONCLUSIONS: Although suitable galenic formulas were developed, no positive effect on TEWL could be observed when ceramide 3B was added in a final concentration of 0.2% (w/v) to different o/w emulsions and applied to SLS-damaged skin. PMID- 11204516 TI - Topical revitalization of body skin. AB - Topical treatments for the body are beneficial for photoageing as well as for specific disease processes, such as scars or striae. Every patient should topically apply photoprotectants in order to prevent photodamage to the skin. Tretinoin can improve body skin and has a documented use in striae. Alpha-hydroxy acids can restore body skin when used on a regular basis. Antioxidants may be of benefit. Scars can be improved with a variety of topically applied agents ranging from silicone gel sheeting to super-potent topical steroids. Chemical peeling for the body can improve the skin with the use of alpha- or beta-hydroxy acids. While topical therapy can improve body skin, adjunctive surgical therapy may be needed to correct body skin disorders or concerns fully. PMID- 11204517 TI - Biosurgery in wound healing--the renaissance of maggot therapy. AB - Chronic wounds are a challenge for modern health care. A basic principle of treatment is the removal of sloughy, necrotic, devitalized tissue to prevent wound infection and delayed healing. Biosurgery (syn. maggot or larval therapy) is a promising adjunct to the whole spectrum of topical treatment methods, in particular for debridement. The term 'biosurgery' describes the use of living maggots on wounds to remove devitalized tissue, decrease the risk of infection and improve wound healing. The present paper gives a brief review of history, entomology, biochemistry and medical indications of biosurgery and the practical handling of maggots. We also provide some clinical data from the literature and our own experience in a wound care unit. Biosurgery is an effective and safe treatment option for debridement and disinfection. PMID- 11204518 TI - Lepromatous leprosy in an HIV-positive patient in Spain. AB - We report a 35-year-old HIV-positive male affected by lepromatous leprosy which, to our knowledge, is the first case of its kind in Spain. The relationship between the two conditions is discussed. PMID- 11204519 TI - Radiation therapy for extensive actinic keratosis. AB - Actinic keratosis in the most common premalignant keratotic tumour of sun-exposed skin. A 66-year-old man developed a large actinic keratosis on his scalp, which did not respond to conventional treatment. Fractionated radiotherapy with a cumulative dose of 28 Gy resulted in complete remission without relapse during a 14-month follow-up. In older subjects in whom conventional treatment fails, low dose fractionated radiation therapy is an effective alternative method. PMID- 11204520 TI - Activation of cutaneous sarcoidosis following Mycobacterium marinum infection of skin. AB - Sarcoidosis has long been associated with mycobacterial infection, especially with Mycobacterium tuberculosis, although a causal association has not been proven. Atypical mycobacteria have also been implicated in causing sarcoidosis, but there is as yet no conclusive evidence. We report the activation of cutaneous sarcoidosis following infection with M. marinum, raising further questions about the role of these bacteria in causing this chronic granulomatous disorder. PMID- 11204521 TI - Photodynamic therapy for in situ squamous cell carcinoma on chronic radiation dermatitis after photosensitization with 5-aminolaevulinic acid. AB - The accessibility of the skin to light treatment, as well as the developments made by dermatologists in photodynamic therapy (PDT), creates an exciting apportunity to include it as a part of our standard therapeutic armamentarium. We report a 63-year-old man with an in situ squamous cell carcinoma located on a chronic radiodermitis area in a finger, treated successfully with PDT. PDT appears to be a viable alternative to conventional therapy for in situ squamous cell carcinoma as well as for other superficial tumours of the skin. PMID- 11204522 TI - Type A Niemann-Pick disease. AB - Niemann-Pick disease (NPD) represents a type of lysosomal storage diseases in which sphingomyelin accumulates in the histocytes and reticuloendothelial cells of the spleen, liver, lymph nodes, bone marrow and central nervous system. We report a child with massive hepatosplenomegaly, lymphadenopathy, mental retardation and widespread papulonodular lesions. His clinical features conform to the type A subgroup of NPD. PMID- 11204523 TI - Recurrent R156H mutation of KRT10 in a Japanese family with bullous congenital ichthyosiform erythroderma. AB - Recently, mutations of keratin 1 gene (KRT1) and keratin 10 gene (KRT10) have been reported in various patients with bullous congenital ichthyosiform erythroderma (BCIE). The substitution of arginine (R) to histidine (H) at amino acid residue 156 (R156H) of coiled 1A region is one of the most frequent mutations of KRT10. In this study, we searched for a mutation in KRT1 and KRT10 in a Japanese family with BCIE and detected mutation R156H in KRT10. Our search led to the detection of R156H. This mutation was not detected in 50 normal individuals. These results confirmed that codon 156 is a frequently mutated site, and that R156H in KRT10 is likely also to be a mutation hotspot in Japanese patients with BCIE. PMID- 11204524 TI - Basal cell carcinoma on the dorsum of the hand: report of 11 cases. AB - BACKGROUND: Basal cell carcinoma (BCC) is the most common cutaneous malignancy, although the appearance on the dorsum of the hand appears to be rare. OBJECTIVES: The purpose of this study was to identify and describe patients with BCC of the dorsum of the hand in a large cohort of BCC patients and to provide a review of the literature. METHODS: Eleven patients with a BCC on the dorsum of the hand were identified. Information on age at diagnosis, sex, treatment and follow up, presence of additional malignancies, etc., was gathered from medical records. RESULTS: Between January 1985 and December 1995, 2990 BCCs were registered, of which 11 were located on the dorsal aspect of the hand (0.37%). Nine patients were male and most patients had a history of multiple skin malignancies. Most of the BCCs were nodular or had a nodular component. Solar elastosis was frequently seen. The percentage of 0.37% compares well with BCC located on the dorsum of the hand in other studies, but also with other parts of the body per skin surface area (except the face and neck area). CONCLUSIONS: The density of BCC on the dorsum of the hand is much lower than in the face and neck area but compares well with other parts of the body. PMID- 11204525 TI - Lycopenaemia. AB - Over the last few years, carotenoids have been studied extensively for their antioxidant activity and the supposed protective effects against cancer, in particular those of the digestive tract. Consumption of carotenoids as anti ageing agents is also widely diffuse. Moreover, the diffusion of slimming and vegetarian diets, and thus the consumption of fruit and vegetables, which contain large amount of carotenoids, is increasing. On the other hand, the excessive dietary intake of carotenoid-containing foods may cause different afflictions characterized by a 'yellow-orange' discoloration of the skin. One of these carotenoids, the lycopene, present in high concentrations in tomatoes, may cause a rare cutaneous disease called lycopenaemia. PMID- 11204526 TI - Pityriasis rosea associated with herpesvirus 7 DNA. PMID- 11204527 TI - Cellular neurothekeoma on the left auricle. PMID- 11204528 TI - Exacerbation of chronic large plaque psoriasis associated with Olanzepine therapy. PMID- 11204529 TI - Bullous pemphigoid in a psoriatic patient. PMID- 11204530 TI - A case of herpes zoster misdiagnosed and treated as unstable angina pectoris. PMID- 11204531 TI - Tuberculosis verrucosa cutis (TBVC). PMID- 11204532 TI - Treatment of oral condylomata acuminata in a HIV-1 patient with bleomycin. PMID- 11204533 TI - Extragenital pigmented lichen sclerosus. PMID- 11204534 TI - Epidermolytic hyperkeratosis (bullous ichthyosis). PMID- 11204535 TI - Primary antiphospholipid syndrome: an aggressive case. PMID- 11204536 TI - A useful criterion of cure in pemphigus vulgaris. PMID- 11204537 TI - Sweet's syndrome with eruption of pustulosis palmaris. PMID- 11204538 TI - Importance of visible lunula in healthy and diseased fingernail plates. PMID- 11204539 TI - Disseminated mucocutaneous blastomycosis in a immunocompetent Indian patient. PMID- 11204540 TI - Predicted wall shear rate gradients in T-type arteriolar bifurcations. AB - The purpose of this study was to examine the theoretical impact of the local bifurcation geometry on the shear rate gradient in a divergent arteriolar-type bifurcation. Newtonian flow through an arteriolar bifurcation was modeled using 3 dimensional computational fluid dynamics (CFD). Branching angles of 30 degrees, 50 degrees, 70 degrees, 90 degrees, 110 degrees, 130 degrees, and 150 degrees were studied at a Reynolds number (Re) of 0.01 in seven separate models. Both the flow split (30%) and the branch to main vessel diameter ratio (4/5) were held constant. Velocity profiles were predicted to deviate significantly from a parabolic form, both immediately before and after the branch. This deviation was shown to be a function of the local bifurcation geometry of each model, which consisted of a branching angle and associated feed-branch intersection shape. Immediately before and after the branch, the shear rate along the lateral branching wall was predicted to exceed (5-fold) that calculated for fully developed flow in the feed. In vivo data were from the anesthetized (pentobarbital, 70 mg/kg) hamster cremaster muscle preparation. Red blood cells were used as flow markers in arteriolar branch points (n = 74) show that a significant gradient in shear rate occurs at the locations and branch shapes predicted by the computational model. Thus, for low Re divergent flow, the gradient in shear rate measured for non-Newtonian conditions, is approximated by a finite element fluid dynamics model of Newtonian flow. PMID- 11204541 TI - Flow around cells adhered to a microvessel wall. I. Fluid stresses and forces acting on the cells. AB - To evaluate the fluid forces acting on cells adhered to a microvessel wall, we numerically studied the flow field around adherent cells and the distribution of the stresses on their surfaces. For simplicity, the cells were modeled as rigid particles attached to a wall of a circular cylindrical tube regularly in the flow direction, in a row or two rows. It was found that not the detailed shape of the model cells but their height from the vessel wall is a key determinant of the fluid forces and torque acting on them. In both arrangements of one row and two rows, the axial spacing between neighboring adherent cells significantly affects the distributions of the stresses on them, which results in drastic variations of the fluid forces with the axial spacing and the relative positions with respect to their neighboring cells. The drag force acting on an adherent cell in the vessel was evaluated to be larger than the value in the 2D chamber flow at the same wall shear stress, mainly due to much larger variations of the pressure distribution on the cell surface in the vessel flow. PMID- 11204542 TI - Correlated expression of adhesive properties for both white and red blood cells during inflammation. AB - The state of leukocyte and erythrocyte adhesiveness/aggregation was determined in the peripheral blood of 382 patients with infection/inflammation as well as in 72 controls by using a simple slide test and image analysis. A highly significant correlation (r = 0.4, n = 455, p < 0.001) was found between the state of leukocyte and erythrocyte adhesiveness/aggregation. The extent of both leukocyte and erythrocyte aggregation correlated with the concentration of fibrinogen. Significant aggregation of leukocytes with erythrocytes was noted as well. We conclude that both leukocyte and erythrocyte aggregation occur in the peripheral blood of patients with infection/inflammation. Such cell aggregation, which might have detrimental rheological consequences, can be detected by using our novel technique. PMID- 11204543 TI - Visualization of flow-dependent concentration polarization of macromolecules at the surface of a cultured endothelial cell monolayer by means of fluorescence microscopy. AB - To substantiate the occurrence of flow-dependent concentration or depletion of atherogenic lipoproteins, which has been theoretically predicted to take place at a blood/endothelium boundary, we have studied the effects of perfusion pressure and wall shear rate on the accumulation and uptake of microspheres by cultured vascular endothelial cells in a monolayer. The study was carried out by flowing a cell culture medium containing fetal calf serum and fluorescent microspheres through a parallel-plate flow chamber having a cultured bovine aortic endothelial cell (BAEC) monolayer on one wall of the chamber. The microspheres had a nominal diameter of 19 nm, approximately the same as that of low-density lipoproteins, and thus served as models and tracers of plasma proteins and lipoproteins. Experiments were carried out in steady flow in the physiological range of wall shear rate and water filtration velocity at the monolayer, while monitoring the intensity of fluorescence of the spheres accumulated at and taken up by the endothelial cells. It was found that in a perfusate containing only fluorescent microspheres, due to increased phagocytic activity of the endothelial cells, the intensity of fluorescence which reflected the number of the microspheres taken up by the endothelial cells, increased almost linearly with time and independently of wall shear rate. However, with perfusates containing fetal calf serum, this abnormal phenomenon did not occur, and the intensity of fluorescence increased with increasing perfusion pressure and decreasing wall shear rate. It was also found that the number of fluorescent microspheres accumulated at and taken up by the BAEC monolayer was shear-dependent only at low wall shear rates, and increased sharply when the flow rate was reduced to zero. These results provided solid experimental evidence that flow-dependent concentration or depletion of macromolecules occurs at the luminal surface of the endothelium at physiological wall shear rates and water filtration velocities, and strongly supports the hypothesis that flow-dependent concentration polarization of lipoproteins plays an important role in the localization of atherosclerosis and intimal hyperplasia in man by facilitating the uptake of atherogenic lipoproteins by endothelial cells. PMID- 11204545 TI - Rheological evidence of the gelation behavior of hyaluronan-gellan mixtures. AB - It was found that solutions of calcium hyaluronate (CaHA) (0.1 to approximately 0.5 wt%) could form a gel by mixing with solutions of sodium type gellan (0.1 to approximately 0.5 wt%), although neither polymer by itself forms a gel at low concentrations (0.1 to approximately 0.5 wt% in this experiment). The rheological properties of CaHA-gellan mixtures were investigated by dynamic and steady shear measurements. Both storage shear modulus G' and loss shear modulus G'' for CaHA gellan mixtures increased with increasing time, and tended to an equilibrium value after 1 h. After reaching steady values of G' and G", the frequency dependence of G' and G'' was observed. G' was always larger than G'' in the accessible frequency range from 10(-2) to 10(2) rad/s. The effects of pH and calcium ions were examined. Gel formation of the mixtures was promoted by decreasing pH and adding from 0.01 to 0.1 M calcium ions, but excessive calcium ions weakened the gel. PMID- 11204544 TI - Biomechanical and morphometric properties of the arterial wall referenced to the zero-stress state in experimental diabetes. AB - Morphometric and passive biomechanical properties were studied in isolated segments of the thoracic and abdominal aorta, left common carotid artery, left femoral artery and the left pulmonary artery in 20 non-diabetic and 28 streptozotocin (STZ)-induced diabetic rats. The diabetic and non-diabetic rats were divided into groups living 1, 4, 8, and 12 weeks after the induction of diabetes (n = 7 for each diabetic group) or sham injection (n = 5 for each group). The mechanical test was performed as a distension experiment where the proximal end of the arterial segment was connected via a tube to the container used for applying pressures to the segment and the distal end was left free. The vessel diameter and length were obtained from digitized images of the arterial segments at pre-selected pressures and at no-load and zero-stress states. Circumferential and longitudinal stresses (force per area) and strains (deformation) were computed from the length, diameter and pressure data and from the zero-stress state data. The zero-stress state was obtained by cutting vessel rings radially causing the rings to open up into a sector. Diabetes was associated with pronounced morphometric changes, e.g., wall thickness. With respect to the biomechanical data, the opening angle increased and reached a plateau in 4 weeks after which it decreased again (p < 0.05). The opening angle was smallest in the thoracic aorta and largest in the pulmonary artery. Furthermore, it was found that the circumferential stiffness of the arteries studied increased with the duration of diabetes. In the longitudinal direction significant differences were found 8 weeks after injection of STZ in all arteries except the pulmonary artery. In the 12 weeks group, the femoral artery was stiffest in the circumferential direction whereas the thoracic aorta was stiffest in the longitudinal direction. The accumulated serum glucose level correlated with the arterial wall thickness and elastic modulus (correlation coefficient between 0.56 and 0.81). PMID- 11204546 TI - Osmotic fragility of the erythrocyte membrane: characterization by modeling of the transmittance curve as a function of the NaCl concentration. AB - The theoretical extinction of blood suspensions submitted to a slow dialysis is analyzed in terms of their NaCl concentration. The model involves two adjustable parameters, chi and K, related to swelling and hemolysis. During swelling, the erythrocyte volume is supposed to vary linearly with the saline concentration. During hemolysis, an exponential decay of the hemoglobin concentration in the erythrocyte is used. The theoretical transmittance curves are consistent with the measurements carried out at a wavelength of 0.808 microm on native and incubated blood samples. Chi and K are relevant parameters to characterize quantitatively the fragility of the erythrocyte membrane. The effect of a non ideal character of the hemoglobin solutions and of normal distributions of chi and K is also discussed. PMID- 11204547 TI - Aggregation behavior and electrophoretic mobility of red blood cells in various mammalian species. AB - Differences of red blood cell (RBC) aggregation among various mammalian species has been previously reported for whole blood, for RBC in autologous plasma, and for washed RBC re-suspended in polymer solutions. The latter observation implies the role of cellular factors, yet comparative studies of such factors are relatively limited. The present study thus investigated RBC aggregation and RBC electrophoretic mobility (EPM) for guinea pigs, rabbits, rats, humans and horses; RBC were re-suspended in isotonic 500 kDa dextran solutions for the EPM and aggregation measurements, with aggregation studies also done in autologous plasma. Salient results included: (1) species-specific RBC aggregation in both plasma and dextran (horse > human > rat > rabbit approximately = guinea pig) with a significant correlation between aggregation in the two media; (2) similar EPM values in PBS for rat, human and horse, a lower value for guinea pig, and a markedly reduced EPM for rabbit RBC; (3) EPM values in dextran with a rank order identical to that for cells in PBS; (4) relative EPM results indicating formation of a polymer-poor, low viscosity depletion layer at the RBC surface (greatest depletion for horse RBC). EPM-aggregation correlations were evident and generally consistent with the Depletion Model for aggregation, yet did not fully explain differences between species; additional studies at various ionic strengths and with various dextran fractions thus seem warranted. PMID- 11204548 TI - Dielectric approach to investigation of erythrocyte aggregation. II. Kinetics of erythrocyte aggregation-disaggregation in quiescent and flowing blood. AB - A method based on dielectric properties of dispersed systems was applied to investigate the kinetics of RBC aggregation and the break-up of the aggregates. Experimentally, this method consists of measuring the capacitance at a frequency in the beginning of the beta-dispersion. Two experimental protocols were used to investigate the aggregation process. In the first case, blood samples were fully dispersed and then the flow was decreased or stopped to promote RBC aggregation. It was found that the initial phases of RBC aggregation are not affected by the shear rate. This finding indicates that RBC aggregation is a slow coagulation process. In the second case, RBCs aggregated under flow conditions at different shear rates and after the capacitance reached plateau levels, the flow was ceased. The steady-state capacitance of the quiescent blood and the kinetics of RBC aggregation after stoppage of shearing depend on the prior shear rate. To clarify the reasons for this effect, the kinetics of the disaggregation process was studied. In these experiments, time courses of the capacitance were recorded under different flow conditions and then a higher shear stress was applied to break up RBC aggregates. It was found that the kinetics of the disaggregation process depend on both the prior and current shear stresses. Results obtained in this study and their analysis show that the kinetics of RBC aggregation in stasis consists of two consecutive phases: At the onset, red blood cells interact face to-face to form linear aggregates and then, after an accumulation of an appropriate concentration of these aggregates, branched rouleaux are formed via reactions of ends of the linear rouleaux with sides of other rouleaux (face-to side interactions). Branching points are broken by low shear stresses whereas dispersion of the linear rouleaux requires significantly higher energy. PMID- 11204549 TI - Antidotes--inappropriate timely availability. AB - The aim of this study was to determine the availability of antidotes to poisons in Wales and the South West of England. A stocklist of antidotes that are available to accident and emergency departments was requested and was compared with recommendations from the International Programme on Chemical Safety (IPCS). Chief pharmacists were invited to complete a short questionnaire regarding knowledge of existing guidelines. Thirty-four of 43 centres replied (response rate 77%). No department held all 36 antidotes (mean 13, range 7-33). All departments held antidotes that were frequently used. Ninety-one percent of departments held one cyanide antidote. Eighty-eight percent held one heavy metal chelating agent. The remaining antidotes were variably stocked. New agents such as 4-methylpyrazole, hydroxocobalamin and the heavy metal chelating agents DMSA and DMPS were infrequently held. Twenty of 34 chief pharmacists were unfamiliar with existing UK guidelines. A trend exists whereby larger departments stocked more antidotes. Some antidotes to poisons are not available in a timely fashion in Wales and the South West of England. There is a lack of awareness of existing guidelines. New recommendations relevant to clinical need and local practice should ideally be developed. PMID- 11204550 TI - Dose-dependent toxicity of diphenhydramine overdose. AB - BACKGROUND: Diphenhydramine (DPHM) overdose is a frequent cause of acute poisoning. Although its clinical features are well known, information about the dose-dependent toxicity of DPHM is still scarce. The objective of this study was to investigate the dose-dependent toxicity of DPHM in patients with acute DPHM poisoning. METHODS: We have analyzed retrospectively all well-documented cases with DPHM monointoxications reported by physicians to the Swiss Toxicological Information Centre (STIC) between January 1984 and April 1996. In addition, a prospective study focusing on ingested DPHM doses and severity of symptoms was performed between May 1996 and December 1998. RESULTS: The retrospective and prospective studies included 232 and 50 patients with DPHM monointoxications, respectively. In both studies, mild symptoms (somnolence, anticholinergic signs, tachycardia, nausea/vomiting) occurred in 55-64%, moderate symptoms (isolated and spontaneously resolving agitation, confusion, hallucinations and ECG disturbances) in 22-27% and severe symptoms (delirium/psychosis, seizures, coma) in 14-18% of patients. Moderate symptoms occurred above ingested doses of 0.3 g DPHM. For severe symptoms the critical dose limit was 1.0 g DPHM. Although the frequency of delirium/psychosis remained constant or even decreased, coma and seizures were significantly (p<0.05) more frequent in the >1.5-g compared with the 1.0- to 1.5-g-dose group. CONCLUSIONS: These data demonstrate a clear dose dependent acute toxicity of DPHM. They indicate that only patients with DPHM ingestions above 1.0 g are at risk for the development of severe symptoms and, therefore, should be hospitalized. Thus, the results contribute to the data basis required for a cost effective management of patients with DPHM overdose. PMID- 11204551 TI - Assessment of thyroid function in pesticide formulators. AB - Thirty male pesticide formulators exposed to the dust and liquid formulation of endosulfan, quinalphos, chlorpyriphos, monocrotophos, lindane, parathion, phorate, and fenvalerate and 20 comparable control subjects from the same area of study were examined for the evaluation of thyroid function tests. The level of TSH was elevated (about 28%) in pesticide formulators as compared to a control group, but the increase was statistically insignificant. Based on the individual TSH measurement, 3 of 30 formulators had isolated elevated levels of TSH and seem to have acquired sub-clinical hypothyroidism; five had TSH values slightly elevated to the upper boarder line (4.03 muIU/ml); and the majority of formulators (N= 22) had TSH values in the normal range varying from 1.29 to 3.9 muIU/ml. Total T3 was suppressed significantly (P< 0.01) in formulators, while marginal decrease (about 7%) was noticed in T4 level. This study indicated thyroid function impairment in few pesticide formulators. PMID- 11204552 TI - Effects of antioxidants and a caspase inhibitor on chloramphenicol-induced toxicity of human bone marrow and HL-60 cells. AB - Chloramphenicol (CAP), a board spectrum antibiotic widely used in many developing countries, has toxic side effects on bone marrow, the most serious of which is aplastic anemia. Recent studies suggest that effects of CAP on suppressing hematopoietic colony formation may be abrogated by antioxidants. In addition, there is preliminary evidence that CAP induces apoptosis in hemopoietic stem cells, leading to aplastic anemia. We have been unable to demonstrate the protective effects of a variety of antioxidants on CAP-induced suppression of burst-forming unit erythroid (BFU-E) and colony-forming unit granulocyte/monocyte (CFU-GM). Using flow cytometry, we have, however, confirmed that CAP can induce apoptosis in purified human bone marrow CD34+ cells. We also showed that a caspase inhibitor, Z-VAD.fmk, can ameliorate the apoptotic-inducing effects of CAP in the HL-60 cell line. PMID- 11204553 TI - Rates of spontaneous reactivation and aging of acetylcholinesterase in human erythrocytes after inhibition by organophosphorus pesticides. AB - The in vitro rates of spontaneous reactivation and aging in human erythrocyte acetylcholinesterase were studied after inhibition by a dimethoxy (R1R2) and diethoxy substituted (R1R2) organophosphate pesticide (OP) of general structure R1R2P(O)X. These have been compared with data for human plasma cholinesterase previously reported using a similar methodology. A significantly slower rate of aging for erythrocyte acetylcholinesterase was found compared to plasma cholinesterase, whether inhibited by dimethoxy or diethoxy substituted OPs. For diethoxy OPs the rate of spontaneous reactivation of the inhibited plasma enzyme was significantly slower than for the inhibited red cell enzyme. This acetylcholinesterase, and previously published plasma cholinesterase, data suggest that in practise a blood sample taken 30-40 h after significant acute OP exposure will still show inhibition in either plasma or erythrocyte cholinesterase when analysed, but that any inhibited plasma enzyme is more likely to be in the aged form. In contrast a substantial proportion of the erythrocyte acetylcholinesterase is found unaged and therefore sensitive to reactivation by oximes. Samples from an occupational exposure where depressions in plasma or erythrocyte cholinesterase activity from baseline measurements were reactivated ex vivo using the oxime 2-PAM support this hypothesis. These data also confirm that the plasma enzyme is a more sensitive than erythrocyte acetylcholinesterase as an indicator of OP exposure and thus the potential value of ex vivo oxime reactivation of erythrocyte acetylcholinesterase in a blood sample to indicate subclinical OP exposure may be limited. However, this study is too small to draw conclusions on the sensitivity of ex vivo oxime reactivation of acetylcholinesterase as a novel biomarker of excessive OP absorption. Given that there is a better relationship between anticholinergic symptoms and red cell acetylcholinesterase inhibition, and that the slower resynthesis rate of any aged or inhibited red cell enzyme may be interpretatively useful when venepuncture is delayed, it is suggested that red cell acetylcholinesterase activity does have a place in monitoring potential OP exposure. PMID- 11204555 TI - Effect of thiamine on the cadmium-chelating capacity of thiol compounds. AB - The influence of thiamine on the efficacy of meso-2,3-dimercaptosuccinic acid (DMSA), diethyldimercapto succinate (DEDMS), alpha mercapto-beta-(2-furyl) acrylic acid (MFA) and alpha-mercapto-beta-(2-thienyl) acrylic acid (MTA) to mobilize cadmium and reverse cadmium-induced biochemical alterations was investigated in cadmium-exposed rats. The thiamine coadministration enhanced the efficacy of MFA and MTA in reducing hepatic and renal burden of cadmium and that of DMSA and DEDMS in mobilizing hepatic cadmium. It also improved the efficacy of DMSA, DEDMS and MFA in reversing the cadmium-induced increase in urinary alkaline phosphatase and aspartate and alanine amino transaminases. The combined treatment with thiamine and DMSA or MFA restricted the urinary loss of zinc and that with thiamine and DEDMS reduced the loss of fecal copper, a general effect of chelation. In conclusion, the administration of thiamine during chelation therapy in cadmium poisoning may be beneficial and more effective than thiol chelating agents alone, which needs to be confirmed in humans. PMID- 11204554 TI - Isoniazid- and rifampicin-induced oxidative hepatic injury--protection by N acetylcysteine. AB - The role of N-acetylcysteine (NAC), a glutathione (GSH) precursor, was investigated in protection against isoniazid- (INH) and rifampicin- (RIF) induced oxidative hepatic injury in young Wistar rats. The hepatotoxic dose of INH and RIF was 50 mg kg(-1) day(-1) each and the hepatoprotective dose of NAC was 100 mg kg(-1) day(-1). All drugs were administered intraperitoneally (i.p.) in sterile water (4.0 ml kg(-1) day(-1)) over a period of 3 weeks. Status of oxidative/antioxidative profiles was the mechanistic approach to assess the hepatotoxicity and/or hepatoprotection. The oxidative injury in INH-RIF co exposed animals was closely associated with significant decline of GSH and related thiols, as well as with compromised antioxidant enzyme system. The oxidative stress was further supported by increased lipid peroxidation observed in these animals. The co-administration of NAC prevented the induction of oxidative stress in INH-RIF co-exposed animals. The amelioration of oxidative stress by NAC was faithfully reflected as normal morphology in these animals, except the presence of mild degree of portal triaditis in one animal co-exposed to INH-RIF and NAC. In contrast, the animals co-exposed to INH-RIF alone showed histological lesions which ranged from intralobular inflammation to patchy necrosis. These results suggest that INH-RIF-induced oxidative injury can be prevented by supporting the cellular antioxidant defense mechanism by NAC. PMID- 11204556 TI - Plasma absorption and ultrastructural changes of rat testicular cells induced by lindane. AB - This paper describes, for the first time, how topical application in rats of a commercial preparation of lindane widely used in public health, at similar doses and routes of administration as in humans, leads to rapid absorption and accumulation of lindane in the testes. An early peak of absorption was detected in plasma 6 h after topical treatment of male Wistar rats with a commercial preparation of 1% lindane (Plomurol). Higher plasma levels were observed after repetitive doses of 60 mg/kg b.w., the amount recommended for the treatment of scabies and pediculosis in humans in several countries. A residue level of 7.4 +/ 0.67 microg/g was found in testicular tissue 6 h after a single daily topical application for 4 consecutive days. The ultrastructural study of testicular interstitial cells exposed to dermal application of lindane (Plomurol) revealed widespread damage of a great number of Leydig cells, some of which were completely disintegrated. PMID- 11204558 TI - TAFI meets the sticky ends. PMID- 11204557 TI - Frequency and Markov chain analysis of amino acid sequences of mouse p53. AB - The amino acid sequence of mouse p53 was measured according to two- and three amino-acid sequences. The measured frequency and probability were compared with predicted frequency and probability. Of 389 two-amino-acid sequences in mouse p53,85 (21.851%) and 27 (6.941%) sequences can be explained by the predicted frequency and probability according to a purelyrandom mechanism. Of 188 non appearing two-amino-acid sequences in mouse p53, 86 (45.745%) and 32 (17.021%) can be explained by the predicted frequency and probability according to a purely random mechanism; no more than two-amino-acid sequences in mouse p53 can be explained by a purely random mechanism. PMID- 11204559 TI - Molecular mechanism of type I congenital heparin cofactor (HC) II deficiency caused by a missense mutation at reactive P2 site: HC II Tokushima. AB - We found a 66-year-old Japanese patient with type I congenital heparin cofactor (HC) II deficiency manifesting multiple atherosclerotic lesions. To investigate the molecular pathogenesis of our patient, we performed sequencing analysis and expressed recombinant human wild-type and mutant HC II molecules in COS-1 and CHO K1 cells. Sequencing analysis following amplification of each of all 5 exons and its flanking region showed a single C to T transition at nucleotide position 12,854 in exon 5, which changed a Pro443 codon (CCG) to Leu codon (CTG). Because this mutation generates a new Bhv I site, the Bbv I digestion pattern of the PCR amplified exon 5 fragments from each family member was analyzed. In all cases, the patterns were consistent with the activities and antigen levels of plasma HC I1 in those members. Transient transfection, metabolic labeling and pulse-chase experiments followed by immunoprecipitation analysis showed that the recombinant mutant HC II molecules were secreted from COS-1 cells in reduced amounts compared with the wild-type, and that an enhanced intracellular association of the mutant molecules with a chaperone, GRP78/BiP, was observed in CHO-K1 cells. Northern blot analysis indicated that the mutant HC I1 mRNA was transcribed at a similar level as that of wild-type. Immunohistochemical staining of the transfected cells revealed that COS-1 cells expressing the mutant HC II molecules were stained mainly in the perinuclear area. We conclude that the impaired secretion of the mutant HC II molecules, due to intracellular degradation, is the molecular pathogenesis of type I congenital HC II deficiency caused by a Pro443 to Leu mutation at reactive P2 site. PMID- 11204560 TI - Fibrinogen Matsumoto V: a variant with Aalpha19 Arg-->Gly (AGG-->GGG). Comparison between fibrin polymerization stimulated by thrombin or reptilase and fibrin monomer polymerization. AB - Fibrinogen Matsumoto V (M-V) is a dysfibrinogen identified in a 52-year-old woman with systemic lupus erythematous. The triplet AGG encoding the amino acid residue Aalpha19 was replaced by GGG, resulting in the substitution of Arg-->Gly. Residue Aalpha19 has been shown to be one of the most important amino acids in the so called 'A' site or alpha-chain knob. The thrombin-catalyzed release of fibrinopeptide A from M-V fibrinogen was only slightly delayed yet release of fibrinopeptide B was significantly delayed. Both thrombin-catalyzed fibrin polymerization and fibrin monomer polymerization were markedly impaired compared to normal fibrinogen. In addition, reptilase-catalyzed fibrin polymerization of M V was much more impaired than thrombin-catalyzed fibrin polymerization. These results indicate 'B' and/or 'b' site of M-V fibrinogen play a more important role in thrombin-catalyzed fibrin polymerization than that of normal control fibrinogen. PMID- 11204561 TI - Antithrombotic efficacy in a rat model of the low molecular weight heparin, reviparin sodium, administered by the oral route. AB - Previous studies in rats show that unfractionated heparin and the low molecular weight heparin logiparin have a dose-dependent antithrombotic effect and are found in endothelium and plasma when administered orally. Objectives of the present study were to determine if similar evidence of absorption could be observed with oral reviparin sodium. Thrombosis incidence was determined 4 h after application of 10% formalin in methanol to the exposed jugular vein. A dose dependent antithrombotic effect was observed when 0.01 to 7.5 mg/kg (20 rats/group) was administered by stomach tube immediately following thrombus initiation. Thrombotic incidence was also significantly reduced when 0.025 mg/kg was given 4 and 2 h prior to, immediately after, and 2 and 3 h following thrombus initiation. Reviparin was recovered from endothelium and plasma in trace amounts at all doses. At 0.025 mg/kg, peak aortic endothelial reviparin concentrations were found at 1 and 2 h and peak plasma anti-Xa activity was detected at 2 h. Trace amounts of plasma TFPI were found only at 8 h after administration. Dose dependent antithrombotic activity and recovery from endothelium and plasma support the hypothesis that orally administered reviparin sodium is absorbed. PMID- 11204562 TI - Factor XII-dependent contact activation on endothelial cells and binding proteins gC1qR and cytokeratin 1. AB - Although proteins of the kinin-forming pathway are bound along the surface of endothelial cells, the mechanism of activation of this proteolytic cascade is unclear. Endothelial cell surface proteins, gC1qR and cytokeratin 1, are capable of binding Factor XII and high molecular weight kininogen (HK) in a zinc dependent reaction thus we considered the possibility that these proteins might catalyze initiation of the cascade. Incubation of Factor XII, prekallikrein, and HK with gC1qR or cytokeratin 1 leads to a zinc-dependent and Factor XII-dependent conversion of prekallikrein to kallikrein. We also demonstrate that normal plasma is capable of activating upon interaction with the cells whereas plasma deficient in Factor XII, prekallikrein and HK do not activate. Normal plasma activation was inhibitable by antibody to gC1qR and cytokeratin 1. Thus, gC1qR and cytokeratin 1, represent potential initiating surfaces for activation of the plasma kinin forming cascade and may do so as a result of their expression along cell surfaces. PMID- 11204563 TI - Immunological assay for the determination of procarboxypeptidase U antigen levels in human plasma. AB - The importance of carboxypeptidase U as a novel regulator of the fibrinolytic rate has attracted a lot of interest recently. In the present work, an ELISA was developed using polyclonal antibodies raised against recombinant proCPU, expressed in DON cells. The assay determines the antigen concentration of the zymogen of carboxypeptidase U, procarboxypeptidase U, in human citrated plasma or EDTA plasma. No interference is observed with plasma carboxypeptidase N. The assay is very reproducible (within-run: 4.6% CV, between-run: 6.8% CV). In a group of 479 healthy individuals the mean proCPU antigen concentration is 13.4 microg/ml (SD 2.5 microg/ml). A good correlation is found with the functional procarboxypeptidase U assay described earlier (r = 0.82, p < 0.0001) (Schatteman K, Goossens F, Scharpe S, Neels H, Hendriks D Clin Chem 1999: 45: 807-813). The significant correlation between the proCPU antigen concentration and the 50% clot lysis time stresses its importance as a player in fibrinolysis control. PMID- 11204564 TI - Mechanism of the immune response to human factor VIII in murine hemophilia A. AB - Mice genetically deficient in factor VII (fVIII) are a model of hemophilia A. As a first step to reproduce in this mouse model what occurs over time in hemophilia A patients treated with human fVIII (hfVIII), we have investigated the time course and the characteristics of their immune response to hfVIII, after multiple intravenous injections. Anti-hfVIII antibodies appeared after four to five injections. They were IgG1 and to a lesser extent IgG2, indicating that they were induced by both Th2 and Th1 cells. Inhibitors appeared after six injections. CD4+ enriched splenocytes from hfVIII-treated mice proliferated in response to fVIII and secreted IL-10: in a few mice they secreted also IFN-gamma and in one mouse IL-4, but never IL-2. A hfVIII-specific T cell line derived from hfVIII-treated mice secreted both IL-4 and IFN-gamma, suggesting that it included both Th1 and Th2 cells. CD4+ enriched splenocytes of hfIII-treated mice recognized all hfVIII domains. Thus, hemophilic mice develop an immune response to hfVIII administered intravenously similar to that of hemophilia A patients. Their anti-hfVIII antibodies can be inhibitors and belong to IgG subclasses homologous to those of inhibitors in hemophilic patients; their anti-hfVIII CD4+ cells recognize a complex repertoire and both Th1 and Th2 cytokines, and especially IL-10, may drive the antibody synthesis. PMID- 11204565 TI - CD63 associates with the alphaIIb beta3 integrin-CD9 complex on the surface of activated platelets. AB - The tetraspanins are integral membrane proteins expressed on cell surface and granular membranes of hematopoietic cells and have been identified in multi molecular complexes with specific integrins. In resting platelets, CD63, a member of the tetraspanin superfamily, is present in dense granule and lysosomal membranes and, following platelet activation, translocates to the plasma membrane. In the present study, platelet activation by thrombin leads to incorporation of CD63 into the Triton-insoluble actin cytoskeletal fraction. This incorporation was inhibited by preincubation of platelets with RGDS or EGTA and did not occur in platelets from a patient with Glanzmann's thrombasthenia, suggesting that it was dependent upon alphaIIbbeta3. In activated platelets, the anti-CD63 MoAb, D545, co-immunoprecipitated CD63 with other surface-labeled proteins, including alphaIIbbeta3 and another tetraspanin, CD9. The association of CD63 with CD9 and alphaIIbbeta3, was not inhibited by preincubation of platelets with RGDS or EGTA. D545 did not inhibit the adhesion of activated platelets to purified extracellular matrix proteins, but significantly decreased adhesion of thrombin-activated platelets to neutrophils in a rosetting assay. D545 also caused disaggregation of platelets stimulated by ADP, but had no effect on aggregation induced by other agonists. These results are consistent with the proposal that CD63 becomes part of an alphaIIbbeta3-CD9-CD63 integrin-tetraspanin complex in activated platelets--an association that may modulate the function of alphaIIbbeta3-dependent interaction with other cells such as neutrophils. PMID- 11204566 TI - Expression of translation initiation factors elF-4E and elF-2alpha and a potential physiologic role of continuous protein synthesis in human platelets. AB - It is generally believed that platelets do not have a functionally significant protein synthetic machinery. However, our analysis demonstrated that normal bone marrow megakaryocytes express high levels of translation initiation factors eIF 4E and eIF-2alpha and the expression of these protein synthesis initiation factors is continued in platelets (as determined by immunohistochemistry and Western blot analysis). Both eIF-4E and eIF-2alpha are key regulators of protein synthesis. The eIF-4E is a rate-limiting part of a multisubunit complex, eIF-4F, that binds to the 5' cap structure present in virtually all eukaryotic mRNAs, and carries out transfer of mRNAs to ribosomes for translation. Translation initiation factor eIF-2alpha is also a rate-limiting protein which associates with two other proteins to form an eIF-2 initiation factor complex responsible for the transfer of initiator methionyl-tRNA to the 40S ribosomal subunit. We confirm that expression of eIF-4E and eIF-2alpha is biologically relevant in that platelets continue protein synthesis, albeit at a 16 times lower rate than WBC (as determined by 35S-labeled amino acid incorporation, SDS-PAGE and scintillation counting). Finally, we determined that protein synthesis inhibitors (puromycin and emetine) attenuate the platelet aggregation response to a combination of ADP and epinephrine, but potentiate the response to collagen. Our data are consistent with the existence of different signal transducing pathways mediating the response to ADP/epinephrine and collagen. We suggest that the ADP/epinephrine response is positively affected by continuously synthesized proteins, while the response to collagen is modulated by continuously produced inhibitory proteins. Taken together, our results suggest that continuous protein synthesis is important for platelet function and its role in platelet physiology and pathophysiology deserves further study. PMID- 11204567 TI - Platelets exposed to elevated levels of endogenous thrombopoietin in vivo have a reduced response to megakaryocyte growth and development factor in vitro. AB - Thrombopoietin (TPO), or megakaryocyte growth and development factor (MGDF), has been shown to potentiate the sensitivity of normal human platelets to various agonists in vitro. The present study investigated the functional and biochemical properties of platelets from mice rendered thrombocytopenic by sublethal irradiation with regard to the reactivity to recombinant murine MGDF (rmMGDF) in vitro. During the course of reversible thrombocytopenia following irradiation, platelets from irradiated mice which had lower platelet counts and reciprocally higher plasma TPO levels showed lower reactivity to rmMGDF in agonist-induced platelet aggregation. Intravenous injections of recombinant soluble murine c-Mpl (sMpl), which has the ability to capture TPO, after irradiation restored the reactivity of platelets at the platelet nadir to rmMGDF. On the other hand, platelets prepared from normal mice 3 h after a single intravenous injection of pegylated rmMGDF did not respond to rmMGDF. There was a marked decrease in c-Mpl and Janus kinase 2 (JAK2) in platelets from irradiated mice at the platelet nadir. Similar results were observed with platelets from mice administered pegylated rmMGDF. JAK2 was only moderately decreased, however, in platelets from mice given sMpl after irradiation. These results indicate that exposure of platelets to increased endogenous TPO levels in vivo in thrombocytopenic mice leads to a reduction in the platelet reactivity to rmMGDF in vitro. Further, these results suggest that the c-Mpl-mediated signaling pathway, which is essential for the priming effect of rmMGDF, is defective in thrombocytopenic murine platelets. PMID- 11204568 TI - Lack of in vivo function of CD31 in vascular thrombosis. AB - A murine model of endothelial cell injury-based vascular thrombosis was used to test the role of platelet-endothelial cell adhesion molecule-1 (PECAM-1, CD31) in blood cell aggregate formation and vessel occlusion in vivo. Photochemically induced thrombus formation was analyzed in detail using intravital fluorescence microscopy of individual microvessels in cremaster muscle preparations of CD31 deficient and wildtype mice. In venules, epi-illumination induced rapid thrombus formation with first platelet deposition after 0.56 +/- 0.11 min and complete vessel occlusion within 5.05 +/- 0.45 min. In arterioles, thrombus formation was markedly delayed with first platelet deposition after 3.03 +/- 0.47 min and complete vessel occlusion within 10.04 +/- 1.26 min. Kinetics of thrombus formation in both venules (first platelet deposition: 0.52 +/- 0.1 min; vessel occlusion: 5.03 +/- 0.52 min) and arterioles (first platelet deposition: 3.06 +/- 0.68 min; vessel occlusion: 10.02 +/- 1.38 min) of CD31-deficient mice was found almost identical compared with that in wildtype animals. Tail bleeding time was 233 +/- 24 s in wildtype and 243 +/- 32 s in CD31-deficient mice. Moreover, CD31 deficient and wildtype mice revealed comparable interaction of leukocytes to endothelium. This study shows for the first time in vivo that CD31 is not critically involved in blood cell thrombus formation upon endothelial cell injury. PMID- 11204569 TI - Serum prostaglandin D synthase level after coronary angioplasty may predict occurrence of restenosis. AB - Lipocalin-type prostaglandin D synthase (L-PGDS), which is responsible for the biosynthesis of PGD2, has recently been found to be present in the atherosclerotic plaque of the human coronary artery and also to be secreted in human serum. We measured the serum L-PGDS level and compared it with the expressions of the platelet membrane surface glycoprotein and neutrophil adhesion molecule in patients undergoing PTCA. The L-PGDS level significantly decreased (P < 0.01) and the platelet surface expression of CD62P (P-selectin) significantly increased (P < 0.01) immediately after PTCA in the coronary sinus blood. Both changes were inversely correlated (R = -0.72, P < 0.001). Although the L-PGDS level in the coronary sinus blood remained equivalent to the baseline level in patients who experienced restenosis, the level increased over the baseline level (P < 0.01) at 48 h after PTCA in patients without restenosis. Neutrophil surface expression of CD11b (alpha subunit of Mac-1) significantly increased at 24 h (P < 0.01) to 48 h (P < 0.001) after PTCA in the coronary sinus blood in patients with restenosis but the change showed less significant in patients without restenosis. The changes in the L-PGDS level and the CD11b expression at 48 h after PTCA were inversely correlated (R = -0.55, P < 0.05). An increased serum L-PGDS level at 48 h after PTCA possibly predicts the avoidance of late restenosis. It is suggested that reduction in PGD2 synthesis triggers platelet activation and that a subsequent increase in the PGD2 synthesis suppresses inflammatory reaction at the intervention site indicated by neutrophil activation and inhibits development of restenosis. Pharmacological or biological intervention that increases endogenous PGD2 synthesis should be tested as a new strategy to prevent restenosis. PMID- 11204571 TI - Exogenous factors from animal sources that induce platelet aggregation. PMID- 11204570 TI - Expression of vascular endothelial growth factor in human monocyte/macrophages stimulated with lipopolysaccharide. AB - Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cells. We have studied the production of VEGF by human macrophages in response to lipopolysaccharide (LPS). Macrophages stimulated with LPS expressed VEGF mRNA and protein in concentration- and time-dependent manners. The LPS-induced expression of VEGF was inhibited by cycloheximide pretreatment, which suggested that synthesis of certain factor(s) is required for the LPS activity. The induction of VEGF was also suppressed by SB203580, an inhibitor of p38 mitogen-activated protein (MAP) kinase. These results suggest that the LPS-induced VEGF expression depends on the p38-mediated expression of c-Jun, which constitutes the AP-1 complex and binds to the AP-1 site in the VEGF promoter. Pretreatment of the cells with dexamethasone did not affect the LPS-induced upregulation of VEGF mRNA but strongly inhibited VEGF protein production, and the involvement of posttranscriptional regulation on VEGF expression by dexamethasone was suggested. The conditioned medium of LPS-stimulated macrophages enhanced the growth of cultured endothelial cells and it was inhibited by an antibody against VEGF. We conclude that macrophages produce VEGF in response to the stimulation with LPS, which may be partly mediated by the p38 MAP kinase pathway. PMID- 11204572 TI - Exogenous inhibitors of platelet aggregation from animal sources. PMID- 11204573 TI - Circulating procoagulant microparticles in women with unexplained pregnancy loss: a new insight. AB - One of the frequently proposed mechanisms for pregnancy losses refers to uteroplacental thrombosis. However the contribution of classical thrombotic risk factors remains questionable and, if real, does not account for a large number of pregnancy losses. The aim of this study was to investigate the presence of circulating procoagulant microparticles, a new marker of cell activation already associated with various prothrombotic clinical settings. Microparticles were assessed by an original prothrombinase assay on platelet depleted plasma obtained from 74 women with a history of pregnancy loss without apparent cause and 50 controls. Patients were studied at least 2 months after the last obstetrical event and were classified into 2 groups: 49 women with at least 3 consecutive spontaneous abortions at or before the 10th postmenstrual week and 25 with at least one fetal death beyond the 10th postmenstrual week. Among the 74 patients, 41 had increased levels of circulating microparticles, 29 belonging to the group of early pregnancy loss (59%) and 12 to the group of late pregnancy loss (48%). The high prevalence of increased levels of procoagulant microparticles in both groups makes this new marker very promising for the understanding, follow up and therapeutical handling of pregnancy loss. PMID- 11204574 TI - The role of the glycoprotein IIb fibrinogen receptor subunit T2622G gene polymorphism (HPA-3) on coronary artery disease and acute myocardial infarction. PMID- 11204575 TI - Von Willebrand factor does not vary during normal menstrual cycle. PMID- 11204576 TI - A rapid assay for the vWF protease. PMID- 11204577 TI - Performances of the VIDAS D-dimer new assay for the exclusion of venous thromboembolism. PMID- 11204578 TI - Relationships between homocysteine, folate and vitamin B12 levels with the methylenetetrahydrofolate reductase polymorphism, in Indians from Western Venezuela. PMID- 11204579 TI - A rebuttal--the Rsal polymorphism in the alpha-fibrinogen gene and response of plasma fibrinogen to physical training. PMID- 11204580 TI - Effects of fluvastatin and bezafibrate combination on plasma fibrinogen, t plasminogen activator inhibitor and C reactive protein levels in coronary artery disease patients with mixed hyperlipidaemia (FACT Study)--a rebuttal. PMID- 11204581 TI - Stroke in young adults: the role of paradoxical embolism. AB - Stroke in young adults may be devastating and frequently no cause can be found. However, there is ample literature to suggest an association between cryptogenic stroke in young people and paradoxical embolisation via a venous to arterial circulation shunt (v-aCS), commonly due to patent foramen ovale (PFO). Although paradoxical embolisation is assumed to be a rare event, this review suggests that it is an important or even dominant cause of stroke in young people and that a transcranial Doppler (TCD) technique may be the investigation of choice to identify v-aCS. PMID- 11204582 TI - Procoagulant microparticles: new insights and opportunities in pregnancy loss? PMID- 11204583 TI - The Glasgow Outcome, APCR and Lipid (GOAL) Pregnancy Study: significance of pregnancy associated activated protein C resistance. AB - Activated protein C (APC) resistance secondary to Factor V Leiden (FVL) is associated with pregnancy failure and pre-eclampsia (PET). In non-pregnant subjects, the degree of resistance to APC relates to venous thrombosis risk. In pregnancy, resistance to APC occurs in the absence of FVL. We investigated, in an unselected prospective longitudinal study of 1,671 pregnant, non-FVL subjects, the relationship of the APC sensitivity ratio (APC:SR) with demographic variables and pregnancy outcome. Lower APC:SR values at 7-16 weeks gestation were observed in subjects who subsequently developed PET (median APC:SR 2.55, IQR 2.29-2.70 vs 2.69, IQR 2.48-2.93, Mann-Whitney U-test p = 0.003) in the current pregnancy. An APC:SR < the median (2.69) at 7-16 weeks was associated with a 2.95-fold increased risk (CI95 1.2-7.4) of PET in the current pregnancy. No relationship between the APC:SR, at any gestation, and fetal loss was observed. An inverse correlation between the APC:SR and birth weight was noted. Higher APC:SRs were observed in blood group O subjects and smokers. An inverse relationship of the APC:SR with age, diastolic blood pressure and total serum cholesterol was observed. PMID- 11204584 TI - Anti-alphavbeta3 antibodies in chronic immune thrombocytopenic purpura. AB - In chronic immune thrombocytopenic purpura (ITP), anti-GPIIb-IIIa (alphaIIbbeta3) autoantibodies have been detected in serum and/or platelet-associated IgG (PAIgG) and considered as one of the major causes. We examined whether anti-alphavbeta3 antibodies might be present in ITP cases because of the similarity between alphavbeta3 and GPIIb-IIIa (alphaIIbbeta3). Modified antigen capture ELISA (MACE) using human umbilical vein endothelial cells (HUVEC) showed the presence of serum anti-alphavbeta3 antibodies in 23 of 80 ITP patients (29%). Cross-adsorption studies between platelets and HUVEC demonstrated that most of anti-alphavbeta3 and anti-GPIIb-IIIa antibodies exclusively reacted with alphavbeta3 and GPIIb IIIa, respectively. Platelet-associated anti-GPIIb-IIIa antibodies did not react with alphavbeta3, either. Interestingly, patients having anti-alphavbeta3 antibodies showed significantly lower platelet counts than negative patients. These results indicate the serum anti-alphavbeta3 antibodies are different ones from the classical anti-GPIIb-IIIa (alphaIIbbeta3) antibodies and would provide a new insight into the pathophysiology of ITP as well as the autoantigenic epitopes on beta3 integrins. PMID- 11204585 TI - Acute deep vein thrombosis: early mobilization does not increase the frequency of pulmonary embolism. AB - Outpatient treatment for acute symptomatic deep vein thrombosis (DVT) was shown to be safe for most patients. However, little is known whether patients treated on an outpatient basis were ambulating or predominantly resting, a factor which may be decisive for the outcome. In the present study 129 DVT patients were randomized to either strict immobilization for 4 days or to ambulate for > or = 4 hours per day under supervision in order to show, whether the old concept of temporary immobilization is superior to early mobilization or not. The DVT diagnosis was based on duplex sonography; all patients were screened for PE at baseline and at day 4 by pulmonary ventilation-perfusion scanning, and were followed up for a total of 3 months. Clinically, changes in leg circumferences and leg pain were evaluated. The frequency of PE at baseline was 53.0% and 44.9% in the immobile and the mobile groups, respectively. During the 4 days observation period new PEs were found in 10.0% and in 14.4% of the immobilized and the ambulating patients (delta 4.4%; 95% CI -0.5 to 13.8; chi2 = 0.596, p = 0.44). The occurrence of new PE was related to the presence of PE at baseline but not to other potential predictors. The magnitude of a decrease in leg circumferences and leg pain was comparable in both groups. No patient died during the 4 day observation period. The total 3 month mortality rate was 3.9% (5 patients; 2 from the immobile, 3 from the ambulating group). All 5 patient suffered from malignancies. The results of this study show in accordance with the trial hypothesis that, regarding the frequency of PE, immobilization is not superior to early mobilization, suggesting that early mobilization is safe. PMID- 11204586 TI - Similar effects of atorvastatin, simvastatin and pravastatin on thrombogenic and inflammatory parameters in patients with hypercholesterolemia. AB - BACKGROUND: Previous studies have suggested that statins exert beneficial effects beyond their favorable lipid lowering effect. Particularly, the modification of thrombus formation and degradation, alteration in inflammatory response, plaque stabilization and improved endothelial function are thought to be responsible for additional reduction of morbidity and mortality due to cardiovascular events. To date, however, it is still unclear whether these effects are elicited by all statins. METHODS AND RESULTS: We set out to compare in a controlled, randomized, double-blind study design the effects of almost equieffective cholesterol lowering doses of three chemically and pharmacokinetically different statins (atorvastatin, simvastatin, pravastatin) on hemostatic and inflammatory markers in 99 hypercholesterolemic patients. At entry and 3 months after onset of statin therapy plasma cholesterol and von Willebrand factor antigen (vWf-Ag), fibrinogen, d-dimer, prothrombin fragment 1+2 (F1.2) and C-reactive protein (CRP) were measured. The effect on plasma values of F1.2, vWf-Ag, d-dimer and CRP was not significantly different between the three treatment groups. The effect of simvastatin on fibrinogen (p = 0.005) was more pronounced than the effects of atorvastatin (p = 0.48 n.s.) and pravastatin (p = 0.15 n.s.). Plasma levels of F1.2 and vWf-Ag (when data of all statins were pooled) were significantly reduced by 7% and 10% versus baseline, respectively. No significant reduction was observed for d-dimer (p = 0.26) and CRP (p = 0.5). Total plasma cholesterol levels decreased significantly (p < 0.0001 in all groups) between 22% and 29% compared to baseline. CONCLUSION: The present study shows similar short-term (3 months) effects of atorvastatin, simvastatin and pravastatin on selected hemostatic and inflammatory parameters in plasma in patients with hypercholesterolemia. Thus, chemical and pharmacological differences between statins appear to exert no major influence on these parameters. PMID- 11204587 TI - Regulation of fibrinolysis in plasma by TAFI and protein C is dependent on the concentration of thrombomodulin. AB - Thrombin activatable fibrinolysis inhibitor (TAFI) is a carboxypeptidase B-like proenzyme, that after activation down regulates fibrinolysis. TAFI is activated by thrombin in the presence of the cofactor thrombomodulin (TM). By stimulation of TAFI activation TM down regulates fibrinolysis, however TM is also a cofactor in the activation of protein C. Activated protein C (APC) can up regulate fibrinolysis by limitine the activation of TAFI via the attenuation of thrombin production. We studied these counteracting fibrinolytic properties of TM in plasma by measuring the activation of TAFI during tissue factor induced coagulation. TAFI activation was stimulated at low concentrations of TM but decreased at higher concentrations of TM. Similarly, the clot lysis times increased at low concentrations of TM but decreased at higher concentrations of TM. The reduction of TAFI activation at high TM concentrations was found to be dependent on a functional protein C pathway. The concentration of TM is therefore an important factor in the regulation of TAFI activation and in the regulation of fibrinolysis. High concentrations of TM result in up regulation of fibrinolysis, whereas low concentrations of TM have a down regulatory effect on fibrinolysis. These results suggest that fibrinolysis might be differentially regulated by TM in different parts of the body depending on the local TM concentration in the vasculature. PMID- 11204588 TI - Costs of outpatient anticoagulant treatment in patients with cerebral and peripheral arterial occlusive disease. AB - BACKGROUND AND OBJECTIVE: Knowledge of the costs of oral anticoagulant (AC) treatment may be relevant for resource allocation. Also, the incremental costs may be compared with other treatments for health care policy decisions. In this report, we have assessed actual costs of anticoagulant therapy in anticoagulation clinics (AC-clinic) in three different settings in the Netherlands. METHODS: Costs of anticoagulant drug supply and costs as a result of INR-adjustment procedures were estimated. We compared the total costs of treatment in patients treated after minor cerebral ischaemia in the Stroke Prevention in Reversible Ischemia Trial (SPIRIT) and in patients treated because of peripheral arterial occlusive disease in the Dutch Bypass Oral anticoagulants or Aspirin Trial (BOA). RESULTS: Costs of monitoring ranged between Euro 6.44 and Euro 9.87 per visit for monitoring at the AC-clinic and at home, respectively. The annual costs of administering anticoagulant drugs ranged between Euro 83 (phenprocoumon) and 107 (acenocoumarol). Variation in the overall actual annual costs of AC treatment was caused by the number of monitoring visits, the distribution of home and clinic visits and, to a lesser extent, the medication used. Annual costs of AC therapy for patients in SPIRIT was Euro 239 and for patients in BOA Euro 312. Overall costs of anticoagulant therapy were about 3 to 4-fold higher than standard treatment with aspirin. CONCLUSIONS: Although the actual costs of anticoagulant therapy may be substantially higher than that of other antithrombotic therapies, its cost-effectiveness depends highly on efficacy. PMID- 11204589 TI - Some patients with antiphospholipid syndrome express hitherto undescribed antibodies to cardiolipin-binding proteins. AB - Contrary to infective anticardiolipin (aCL) antibodies, autoimmune aCL antibodies react with phospholipids (PL) mainly via binding to the plasma glycoprotein cofactor beta2-Glycoprotein I (beta2GPI). While there is a well-documented link between the risk of thrombosis and the presence of beta2GPI-dependent anticardiolipin antibodies, the pathological impact of other antiphospholipid antibodies is less clear. By means of cardiolipin affinity-chromatography, we isolated and identified 3 CL-binding proteins, complement component C4, complement factor H and a kallikrein-sensitive glycoprotein, and tested for the presence of autoantibodies against these proteins in patients with antiphospholipid syndrome (APS), systemic lupus erythematosus (SLE) and other autoimmune diseases. High titers of autoantibodies to C4 as compared to age- and sex-matched healthy controls were present in 3 of 26 patients with APS, and weak titers were found in 2 of 26 patients with SLE and in none of 26 patients with other autoimmune diseases. Autoantibodies to complement factor H were found in 4 APS, 3 SLE and none of the other autoimmune patients. Autoantibodies to kallikrein-sensitive glycoprotein were detected in 6 APS patients, 1 SLE patient, and 1 patient with another autoimmune disease. A close relationship between these antibodies was found, suggesting their origin from a common macromolecular complex. However, no relationship with anti-beta2GPI antibodies was found, with the three patients with higher levels of autoantibodies having a low titer of anti-beta2GPI antibodies. In conclusion, some patients with APS harbor circulating antibodies to other CL-binding proteins which might be useful to further characterize these patients. PMID- 11204590 TI - High levels of adhesion molecules are associated with impaired endothelium dependent vasodilation in patients with peripheral arterial disease. AB - Soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cellular adhesion molecule-1 (sVCAM-1) were measured alongside flow-mediated vasodilation (FMD) in 34 patients with intermittent claudication and 14 control subjects. Patients with plasma sICAM-1 >253 ng/mL (median value) showed lower FMD than those with sICAM-1 < 253 ng/mL (5.6 +/- 1.8% vs 9.6 +/- 4.2%, p < 0.01). Similarly, in the 17 patients with plasma sVCAM-1 > 414 ng/mL, FMD was lower than in the remaining 17 patients (6.1 +/- 1.9% vs 9.2 +/- 4.5%, p < 0.05). Additionally, when endothelial dysfunction was defined as FMD < or = 5.5%, patients with FMD below this value had higher plasma concentrations of sICAM-1 and sVCAM-1 than those with FMD > 5.5%. Therefore, our findings indicate a close association between elevated plasma levels of adhesion molecules and endothelial dysfunction. As impaired endothelial function is one of the first steps in atherogenesis, our findings have clinical relevance since they serve as the basis for further evaluation of sICAM-1 and sVCAM-1 as potential plasma markers for progression of atherosclerosis in a population at high risk. PMID- 11204591 TI - Gene-environment and gene-gene interaction in the determination of plasma homocysteine levels in healthy middle-aged men. AB - Healthy middle-aged men (n = 1,470) from eight general practices across Britain were examined for plasma total homocysteine levels and genotyped for the A222V polymorphism in the methylene-tetrahydrofolate (MTHFR) gene, the 68 bp insertion polymorphism in exon 8 of the cystathionine b synthase (CBS) gene and the D919G polymorphism in the methionine synthase (MS) gene. The median value for plasma homocysteine was 11.90 micromol/l (25-75% Interquartile range 10.10-14.20) for the whole sample. Smokers had significantly higher homocysteine levels than non smokers (12.90 vs 11.70 micromol/l and p < 0.00005) and levels significantly differed according to folate (p-value < 0.00005), with men in the lowest quartile of folate having the highest median homocysteine levels. Genotype at all three loci was associated with differences in plasma homocysteine level. Individuals homozygous for the MTHFR V222 allele had 1.6 micromol/l higher median homocysteine levels when compared to the other two genotypes (p < 0.00005), while for the CBS and MS genes, individuals carrying one or more of the rare alleles had lower median homocysteine than individuals homozygous for the common allele (0.80 micromol/l, p < 0.03, and 0.70 micromol/l, p < 0.04 respectively). The raising effect associated with homozygosity for the V222 allele was greater in men in the lowest quartile of folate (interaction between folate and genotype p = 0.02), but none of the genotype effects was significantly modulated by B12 levels. While the raising effects of V222 and MS D919 homozygosity on homocysteine level were essentially additive, the homocysteine lowering effect associated with the CBS 68bp allele was seen most strongly in men homozygous for the V222 allele (MTHFR-CBS genotype interaction p = 0.03) and the D919 allele (MS CBS interaction p = 0.09). Age, folate, B12 and smoking explained 13.48% of the variance while the three genotypes combined and with interaction terms explained only an additional 2.63%. This interaction between CBS genotype and MTHFR and MS genotype points to a key role of the CBS transulphuration pathway in the metabolism of homocysteine that may be particularly important as a compensatory mechanism in subjects with low dietary folate. PMID- 11204592 TI - Functional properties of factor V and factor Va encoded by the R2-gene. AB - Carriership of the factor V (FV) gene marked by the R2-haplotype, a series of linked polymorphisms encoding several amino acid changes in FV, is associated with mild resistance to activated protein C (APC) and with an increased risk of thrombosis. We compared the functional properties of normal FV(a) and R2-FV(a) in model systems and in plasma. FV and R2-FV were equally well activated by thrombin and expressed identical cofactor activities in prothrombin activation. Rate constants of APC-catalyzed inactivation of FVa and R2-FVa were similar both with and without protein S. However, significant differences were observed between haemostatic parameters determined in plasma from homozygous carriers of the R2 gene (n = 5) and age-matched non-carriers (n = 19). Plasma from R2-carriers contained significantly lower FV levels and the ratio of the two FV isoforms (FV1 and FV2) was shifted in favor of FV1. The FV2/FV1 ratio was 1.4 (95% CI = 1.3 1.5) in homozygous carriers of R2 and 2.8 (95% CI = 2.5-3.1) in controls (p < 0.00001). In an APC resistance test which quantifies the cofactor activity of FV in APC-catalyzed FVIII(a) inactivation, homozygous R2-carriers had significantly lower (p < 0.00001) APC sensitivity ratios (APCsr = 1.54, 95% CI = 1.48-1.60) than controls (APCsr = 2.17, 95% CI = 2.05-2.28). This indicates that R2-FV has reduced cofactor activity in APC-catalyzed FVIII(a) inactivation. The changes of the relative amounts of FV1 and FV2 in carriers of the R2-gene will result in increased thrombin formation in the presence of APC and may provide a mechanistic explanation for the increased thrombotic risk associated with the R2-haplotype. PMID- 11204593 TI - Genetic screening of candidate genes for a prothrombotic interaction with type I protein C deficiency in a large kindred. AB - The incomplete penetrance of thrombosis in familial protein C deficiency suggests disease occurs when this deficit is combined with additional abnormalities in the hemostatic system. The pattern of inherited thrombophilia in the Vermont II kindred, which is affected by a clinically dominant type I protein C deficiency, provides strong evidence for a second unidentified gene that segregates independently of protein C deficiency and increases susceptibility to thrombosis. To test the second gene hypothesis, thirty-four candidate genes for proteins involved in hemostasis or inflammation were tested as the unknown defect, using highly polymorphic short tandem repeat (STR) markers in an informative subset (n = 31) of the kindred. The genes considered are; alpha-fibrinogen, beta fibrinogen, gamma-fibrinogen, prothrombin, tissue factor, factor V, protein S, complement component 4 binding protein, factor XI, factor XII, factor XIIIa, factor XIIIb, histidine rich glycoprotein, high molecular weight kininogen, kallikrein, von Willebrands factor, platelet factor 4, thrombospondin, antithrombin III, alpha-1-antitrypsin, thrombomodulin, plasminogen, tissue plasminogen activator, urokinase plasminogen activator, plasminogen activator inhibitor-1, plasminogen activator inhibitor-2, protein C inhibitor, alpha-2 plasmin inhibitor, kallistatin, lipoprotein a, interleukin 6, interleukin 1, cystathionine-beta-synthase, and methylenetetrahydrofolate reductase. Mutations in many of these genes have been previously established as independent risk factors for thrombosis. However, linkage analysis provided no evidence to implicate any of the candidate genes as the second inherited factor that promotes thrombophilia in this kindred. PMID- 11204594 TI - Genetic regulation of plasma levels of vitamin K-dependent proteins involved in hematostatis: results from the GAIT Project. Genetic Analysis of Idiopathic Thrombophilia. AB - Vitamin K-dependent proteins play a critical role in hemostasis. We have analysed the genetic and environmental correlations between measures of several vitamin K dependent proteins in 21 Spanish extended families, including 397 individuals. Plasma functional levels of factors II, VII, IX, X, protein C and functional protein S were assayed in an automated coagulometer. Antigenic levels of total and free protein S were measured using an ELISA method. A maximum likelihood based covariance decomposition analysis was used to assess the heritability of each trait and the genetic and environmental correlations between all possible pairs. All of the plasma levels had a significant genetic component (heritability) ranging from 22% to 52% of the phenotypic variance. Among the 28 possible pairs of genetic correlations, 18 were significant at a level of p < 0.05 and six exhibited a p-value between 0.05 and 0.10. Positive environmental correlation was observed for 25 of the pairs (p < 0.05). We conclude that genetic effects account for a large proportion of the observed phenotypic variation in vitamin K-dependent proteins. Some of the genes appear to pleiotropically influence all of these traits, since most pairs of phenotypes exhibit significant genetic correlation. However, since these phenotypes show a high degree of environmental correlation, it is also likely that the same environmental factors influence them co-jointly. PMID- 11204595 TI - Structural and functional characteristics of the B-domain-deleted recombinant factor VIII protein, r-VIII SQ. AB - Recombinant factor VIII SQ (r-VIII SQ), ReFacto, is a recombinant factor VIII product similar to the smallest active factor VIII protein found in plasma derived factor VIII (p-VIII) concentrates. The protein comprises two polypeptide chains of 80 and 90 kDa and lacks the major part of the heavily glycosylated B domain i.e. amino acids Gln744 to Ser1637. r-VIII SQ retains six potential glycosylation sites for N-linked oligosaccharides at asparagine residues 41, 239, 582, 1685, 1810 and 2118. We describe a thorough comparison of the characteristics of r-VIII SQ with those of p-VIII. The primary and secondary structures of r-VIII SQ were in good agreement with that of B-domain-deleted p VIII (p-VIII-LMW) as shown by SDS-PAGE, Western blotting with antifactor VIII antibodies, tryptic mapping, amino acid sequence analysis and circular dichroism spectroscopy. A few divergences also existed. Thus r-VIII SQ was shown to contain a small amount of the single chain primary translation product of 170 kDa and also the product specific sequence of 14 amino acids, the SQ-link, in the C terminal end of the 90 kDa chain. It was shown that r-VIII SQ had a high specific activity of about 14,000 IU VIII:C/mg as determined by use of a chromogenic substrate assay. The r-VIII SQ protein was comparable to p-VIII forms with a retained B-domain, in terms of potency measured by a chromogenic substrate or a two-stage clotting assay, in interactions with thrombin, and with activated protein C (APC) in combination with Protein S. The ability of r-VIII SQ to participate as a cofactor in factor Xa generation in a mixture of factors IXa and X, phospholipid and calcium was in conformity with that of p-VIII. Furthermore r VIII SQ had a good binding capacity for phospholipid vesicles and von Willebrand factor (vWF) as shown in gel filtration studies. The same kinetics in binding to von Willebrand factor was found for r-VIII SQ and p-VIII as determined by real time biospecific interaction analysis (BIA) with use of the BIAcore instrument. The apparent association rate constant was 4 x 10(6) M(-1)s(-1). Two dissociation rate constants were found, 1 X 10(-2)s(-1) and 4 x 10(-4)s(-1). The results extend the present knowledge that the factor VIII B-domain is dispensable for the factor VIII cofactor function in hemostasis. PMID- 11204596 TI - Dermatology: 2001. PMID- 11204597 TI - Recurrent lumbosacral herpes simplex in the bedridden hospitalized patient. AB - A clinical variant of genital herpes simplex virus (HSV) infection, recurrent lumbosacral HSV, occurs in bedridden hospitalized patients. We want to call attention to an uncommon pattern of HSV infection in the hospitalized bedridden patient seen by the dermatology consultation service in a large university hospital. HSV is characterized by a mixture of recurrent groups of herpetic vesicles in all stages of development, with multiple, persistent hyperpigmented patches bilaterally distributed over the lumbosacral (buttocks) area. PMID- 11204598 TI - Perioral dermatitis: an acneiform eruption. PMID- 11204599 TI - Botanical briefs: the scourge of India--Parthenium hysterophorus L. PMID- 11204600 TI - Benign lymphangioendothelioma manifested clinically as actinic keratosis. AB - Benign lymphangioendothelioma is an acquired lymphangiectatic lesion that must be recognized and differentiated from angiosarcoma, early Kaposi's sarcoma, and lymphangioma circumscriptum. We report the case of a 68-year-old woman with the clinical presentation of a possible actinic keratosis and the typical histologic findings of benign lymphangioendothelioma and an overlying actinic keratosis. PMID- 11204601 TI - A case of lichen striatus following Blaschko lines. AB - We present a case of lichen striatus (LS) in a 36-year-old woman with skin lesions on the right side of the chest distributed along Blaschko lines that showed a swirling s-shaped pattern. The differential diagnosis of LS includes a variety of nevoid and acquired conditions following Blaschko lines, particularly acquired relapsing self-healing Blaschko dermatitis. The extent to which these 2 conditions overlap remains contentious. PMID- 11204602 TI - Dissecting cellulitis in a white male: a case report and review of the literature. AB - Dissecting cellulitis is an uncommon, chronic, progressive suppurative disease of unknown etiology. It is characterized by painful papules and nodules, interconnecting sinus tracts, purulent drainage, and scarring alopecia. This disease predominately affects young black men, but is rarely reported in white males. The refractory nature of this process makes treatment difficult. We report a case of dissecting cellulitis in a white male, which responded to oral isotretinoin. PMID- 11204603 TI - Recurrent disseminated herpes zoster and cytomegalic perianal ulcer: a case report and review of the literature. AB - We describe a patient with lymphocytic leukemia who developed multiple, disseminated, vesiculopustular eruptions in combination with perianal ulcer. Four years earlier, she had a herpes zoster (HZ) infection involving the ophthalmic division of her left trigeminal nerve with subsequent postherpetic neuralgia that was treated with steroids. After the studies, we concluded that the patient had a recurrent disseminated HZ infection and perianal ulcer caused by cytomegalovirus (CMV). PMID- 11204604 TI - Carbamazepine hypersensitivity syndrome mimicking mycosis fungoides. AB - We report a case of a patient who experienced a generalized skin rash with systemic involvement 2 months after beginning carbamazepine treatment for trigeminal neuralgia. Skin biopsy specimens suggest mycosis fungoides. Complete remission of the clinical and pathologic changes after drug discontinuation and the positive result of carbamazepine from an epicutaneous test suggest a diagnosis of pseudolymphoma due to carbamazepine. PMID- 11204605 TI - Generalized seborrheic dermatitis in an immunodeficient newborn. AB - We report the case of a female infant with failure to thrive, generalized seborrheic dermatitis, and intermittent diarrhea. Results of laboratory investigation revealed low serum immunoglobulin G IgG levels. She failed to gain additional weight and experienced recurrent infection. She died 3 months later. PMID- 11204606 TI - Cutis photo quiz. Lupus erythematosus and dermatomyositis. PMID- 11204607 TI - Squamous cell carcinoma of the nail bed: is finger predominance another clue to etiology? A report of 5 cases. AB - Although squamous cell carcinoma (SCC) is commonly found on sun-exposed skin, the occurrence of this malignancy in the nail bed is rare. We report 5 cases of SCC of the nail bed and suggest that the disproportionate number of neoplasms of this type on the second, third, and fourth fingers, combined with the known relationship of SCC and human papillomavirus (HPV), is evidence that most SCC of the nail bed result from contact with HPV. Moreover, we suggest that patients who present with new, verrucous lesions of the nail bed and have a history of cervical dysplasia, cervical carcinoma, or condyloma acuminata undergo diagnostic biopsy as opposed to traditional destructive therapy for a lesion presumed benign. PMID- 11204608 TI - Persistent peripheral eosinophilia and cutaneous non-Hodgkin's lymphoma: a case report and review of the literature. AB - Peripheral eosinophilia can be the presenting sign in many cutaneous diseases but is often missed as a marker of a serious undiagnosed underlying disease such as atopic dermatitis, urticaria, drug eruption, bullous pemphigoid, inflammatory bowel disease, helminthic infection, Churg-Strauss syndrome, rheumatoid arthritis, or lymphoma. We report a case of non-Hodgkin's lymphoma presenting as persistent eosinophilia with a diffuse nodular cutaneous eruption. PMID- 11204609 TI - Giant basal cell carcinoma and cigarette smoking. AB - Several recent studies have linked cigarette smoking to an increased risk of squamous cell skin cancer, but previous studies have found no correlation between smoking and basal cell carcinoma. This article is a retrospective chart review of 200 patients who had Mohs' surgery for basal cell carcinoma at the Mayo Clinic in Rochester, Minnesota, between 1986 and 1990. In patients with tumors less than or equal to 1.0 cm, 30% were smokers. In patients with tumors 1.1 to 2.0 cm, 42% were smokers. In patients with tumors 2.1 to 4.9 cm, 56% were smokers; and in patients with tumors greater than or equal to 5.0 cm, 50% were smokers. Cigarette smoking is associated with an increased prevalence of basal cell carcinomas larger than 1.0 cm in diameter. PMID- 11204610 TI - Cutaneous infection with Mycobacterium xenopi. PMID- 11204611 TI - Sutureless vasovasostomy using new vascular closure staples in rats. AB - To evaluate the efficacy of sutureless vasovasostomy using vascular closure staples, 20 male Sprague-Dawley rats were used for the study. In each rat, a sutureless vasovasostomy using vascular closure staples was performed on a randomly selected side, and a conventional end-to-end microsutured anastomosis was performed on the opposite side. Operation time was significantly shorter for sutureless vasovasostomy using vascular staples (p < .001). Four weeks after the surgery, however, patency rate and granuloma formation were not different for conventional end-to-end vasovasostomy vs. sutureless vasovasostomy. These findings suggest that sutureless vasovasostomy is simple to perform and requires fewer special technical skills. This procedure may provide an alternative to the conventional vasovasostomy. PMID- 11204612 TI - Sperm aggregation by water extracts from two Bursera species. AB - Some plants have more than the common utility value, as is the case of some members of the Bursera species such as the Mexican copal, a plant used for worship. Water extracts of several plants have vaginal contraceptive properties. The authors evaluated the sperm agglutinating activity of two Bursera species on human and boar sperm. Extracts from stems and leaves were obtained. Capacitated sperm samples were used in all cases. There were different agglutinating capacities, which were not observed in the vehicle-only samples. The most frequent sperm agglutination response was that involving the heads. Agglutinating activity was higher from stem- than leaf-derived extracts. The results indicate that proteins present in the extracts are responsible for the aggregation of sperm heads. PMID- 11204613 TI - Transillumination to evaluate spermatogenesis: effect of testosterone enanthate in adult male rats. AB - The present study has been designed to determine which stages of seminiferous cycle were modified by in vivo intramuscular administration of one or two doses of 25 mg of testosterone enanthate. Testicular weight was significantly reduced after treatment with two doses of testosterone enanthate (p < .05). Assessment of total lengths of stages per 100 mm of seminiferous tubules scored by transillumination showed that testosterone enanthate increased significantly the length of stages VI-VII, but it reduced total lengths of stages I, XII, and XIII XIV. A dose-dependent reduction in the absolute and relative frequency of stage I was observed with testosterone enanthate treatment, whereas stages VI-VII were significantly increased. Analysis of relative frequencies of stages showed that stages XIII-XIV and stages I-V were significantly below the control value (1), whereas stages VI-VIII were over 1. In summary, results of the present study showed that transillumination is an adequate technique to assess the effect of drugs on spermatogenesis, and that testosterone enanthate modifies the pattern of the stages of the seminiferous epithelium cycle, before testicular weight is affected. PMID- 11204614 TI - Evidence for the binding of a human sperm component with diaphanous protein. AB - The YWK-II component of human sperm membrane is related to the betaA4-amyloid precursor protein (APP) of Alzheimer's disease. A yeast 2-hybrid system was used to screen a mouse testis cDNA expression library for potential ligands capable of interacting with the extracellular domain of the YWK-II component. One of the bound proteins was identified as hDIA1, which has 96% identity with p140mDia. These proteins are members of the formin homology family and participate in cytokinesis and organization of the actin cytoskeleton. By interacting with these diaphanous proteins, the YWK-II component may be involved in germ cell differentiation and in the structural formation of the acrosome. PMID- 11204615 TI - Computerized semen analysis (CASA): effect of semen concentration and chamber depth on measurements. AB - The purpose of this study was to examine the influence of sample concentration and chamber depth on the performance of a real-time analysis computer-assisted semen analysis system, the Hobson Sperm Tracker. Fresh semen samples were provided by patients or donors who attended the author's clinic. The samples were used to estimate total concentration, percentage motility, and sperm kinematics. A considerable variation was found in total concentration and motility recordings between manual and computerized analysis, which was more profound in high-density samples (>80 x 10(6) sperm/mL). The sperm motion parameters were significantly different between low- and high-density samples. This difference could not have been due to sample variation since it was also observed after 1:10 dilution of dense samples. The results indicate that a real-time analysis system can be used clinically for semen analysis over a wide range of sperm concentration. However, high sperm concentration can distort sperm count, motility, and sperm kinematics recordings. PMID- 11204616 TI - Cisplatin-induced germ cell apoptosis in mouse testes. AB - The purpose of this study was to investigate whether exposure of male mice to cisplatin induces apoptosis in male germ cells and the possible role of apoptosis in cisplatin-induced testicular damage. Forty-eight male BALB/c mice were divided into cisplatin and control groups. The mice from the cisplatin group received a single intraperitoneal injection of cisplatin of either 1, 5, or 10 mg/kg. The control group received a single intraperitoneal injection of saline alone. The testes were removed on days 1, 3, and 7 after cisplatin administration, respectively. Following histological examination, apoptotic indices (AIs) were measured within seminiferous tubules of the mouse testes by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. A low incidence of spontaneous apoptosis was observed in controls, particularly in spermatogonia and spermatocytes of the mouse testes. After cisplatin administration, both increased Als and decreased spermatozoa and spermatids were found in the seminiferous tubules of the mouse testes. Cisplatin-induced apoptosis was found in spermatogonia, spermatocytes, and spermatids of the mouse testes. In comparison to the control values, AIs increased 2.6- to 6.8-fold in cisplatin-treated mouse testes. AIs reached the highest level on day 1 following 1 mg/ kg, on day 3 following 5 mg/kg, and on day 7 following treatment of 10 mg/kg cisplatin. The study showed that cisplatin-induced germ cell apoptosis in the mouse testes was related to both the dose response and the time course of response. It is suggested that cisplatin-induced germ cell apoptosis may result in decreased spermatogenesis, and the higher dose of cisplatin may delay the occurrence of apoptosis in the mouse testes. PMID- 11204617 TI - Morphological alterations and intratubular lipid inclusions as indicative of spermatogenic damage in cimetidine-treated rats. AB - Doses of cimetidine (50 mg/kg b/w) were administered to adult male Wistar rats over 52 consecutive days. Besides plasma testosterone levels, morphological and morphometric aspects of the seminiferous tubules as well as histochemical analysis of the lipid content by oil red O were emphasized. Abnormal tubules exhibiting disorganization of their cellular association, loss of germ cells, and multinucleated giant spermatids were usually found. Significant reductions of testis weight and tubular diameter at specific stages (VII-IX), as well as lack of contact between Sertoli cells and spermatids in tubules at stage IX, suggest a possible interference of cimetidine on the histoarchitecture of the seminiferous epithelium. The dense concentration of lipid inclusions in tubules at postspermiation stages indicates phagocytosis and degradation of germ cells. Since no change in serum testosterone levels was verified in cimetidine-treated rats, the authors could not exclude the possibility that besides an antiandrogenic effect, other biochemical factors necessary for normal spermatogenesis could be involved in the testicular alterations. PMID- 11204618 TI - Postnatal changes in the calcium binding proteins of mouse testis. AB - To define the changes in calcium-binding proteins (CBPs) of mouse testis during postnatal development, testicular protein extracts were analyzed by mobility shift after Ca2+ binding (MSACB) in the 2-dimensional SDS-PAGE. In the adult testis extracts, 29 kinds of protein spots showed mobility shift in the gel containing Ca2+. Among them, 2 spots showed nonspecific mobility shift and 4 spots showed Zn2+ shift. Drastic changes in expression of high-Mr CBPs (Mr > 25 kDa) were observed in testis 3 weeks after birth, suggesting that their expressions were developmentally changed. There was no obvious difference in the qualitative patterns of CBP between 4-week-old testis and adult testis. There was a large mass of CBPs (Mr = 20-25 kDa) expressed constitutively in testis throughout the postnatal development. Degree of MSACB (Mr on the diagonal line/Mr of shifted point in Ca2+ gel) of each spot was in the range of 1.1-1.7 in 12% acrylamide gel. These results suggest that changes in CBPs of testis are closely related with progression of spermatogenesis in mouse testis. PMID- 11204619 TI - Magnesium in human semen: possible role in premature ejaculation. AB - Although magnesium is involved in many biological process and it is found higher levels in semen than serum, its role in human semen has not been elucidated. This investigation was conducted to evaluate the relationship between premature ejaculation and the levels of seminal magnesium. The levels of magnesium, zinc, copper, and selenium were evaluated with an atomic absorption spectrophotometer in serum and seminal plasma in 3 groups of men: (a) normal sperm parameters (15) (b) oligoasthenozoospermia (15), and genuine premature ejaculation (9). There were normal serum and semen levels of all the elements in the three groups, but significantly lower seminal plasma magnesium levels in men with premature ejaculation. The hormonal profile, body mass index (BMI) had no association with premature ejaculation. Decreased levels of magnesium gives rise to vasoconstriction from increased thromboxane level, increased endothelial intracellular Ca2+, and decreased nitric oxide. This may lead to premature emission and ejaculation processes. Magnesium is probably involved in semen transport. More research into the role of magnesium in the male physiology of reproductive tract, especially its association with premature ejaculation, is advocated. PMID- 11204620 TI - The effect of an infertility diagnosis on treatment-related stresses. AB - The purpose of this study was to determine the effect of an infertility diagnosis on treatment-related stresses. One hundred infertile Chinese couples participated in this study. Three structured questionnaires were used to analyze the differences between husbands and wives. As a group wives appear to experience significantly more stress from infertility tests and treatment than their husbands, regardless of whether female infertility was present. Husbands with mixed or idiopathic infertility experienced less stress to infertility than husbands with only male infertility or female infertility. Wives with mixed or idiopathic infertility experienced less stress to infertility than wives with only a female infertility. Marital duration, time in treatment, and the number of AIH or IVF procedures were positively related to the wives' stress level, whereas only number of IVF procedures was positively related to the husbands' stress level. Interventions to enhance the infertility treatment experience are suggested. PMID- 11204621 TI - Epididymal scanning electron microscopy study in hypothyroid rats. AB - The purpose of this research was to investigate, using scanning electron microscopy, the effect of hypothyroidism on the ultrastructure of the rat cauda epididymis. Thyroidectomy was obtained by ip injection of 270 muCi of 131I per rat. One month later, several portions of cauda epididymis were examined. Morphological and physiological differences were detected in the cauda epididymis of the hypothyroid animals when compared to the control normal rats. The hypothyroid condition was associated with important changes in the luminal surface of the cauda epididymis epithelium. Broken, oblique, and loss of stereocilia, denuded epithelial cells, and flattening of the tubule were observed. The results confirm that hypothyroidism causes marked structural changes in the cauda ductus epididymis and could be adversely affect sperm maturation motility. PMID- 11204622 TI - Reevaluation of testicular biopsies of males with nonobstructive azoospermia in assisted reproductive technology. AB - Spermatogenesis was investigated in seminiferous tubules of 100 males with nonobstructive azoospermia. Forty-four (44%) cases had Sertoli-cell-only syndrome, 23 (23%) had spermatogonium in the tubules, 17 (17%) had primary spermatocyte in the tubules, and 16 (16%) had round or late spermatid in the tubules. No cases showed secondary spermatocyte present in the tubules. The mean serum follicle-stimulating hormone (FSH) in males with nonobstructive azoospermia was significantly higher than that in males with obstructive azoospermia (p < .001). The mean concentrations of serum FSH in cases with Sertoli-cell-only syndrome and spermatogonium in the tubules were significantly higher than those in cases with primary spermatocyte and spermatid in the tubules (p < .05-.001). The results indicate that the evaluation of testicular histology using the type of germ cells present in seminiferous tubules is available for assisted reproductive technology. PMID- 11204623 TI - [Apoptosis during spinal cord trauma: prospects for pharmacological correction]. AB - Spinal trauma is a serious problem of modern medicine. The morphological studies illustrate the presence of two alternative pathways of cell destruction in the injured spinal cord: immediate necrotic damage and delayed apoptotic destruction of cells. The apoptosis continues for about 14 days after trauma, and it involves both neurons and glia on a significant distance from the traumatic zone. In this review, the basic stages of apoptosis in spinal cord, biochemical regulation of this process, and methods for its detection are considered. The fact, that apoptosis is a normal cell death process, and that it has reversible stages allows to consider a possibility of pharmacological correction of apoptosis. The special attention is paid to anti-apoptotic therapy with the use of antisense oligodeoxynucleotides and to the perspectives of gene therapy. PMID- 11204624 TI - [Limited proteolysis of integrin alpha v beta3 from human placenta]. AB - Purification of alpha v beta 3 integrin from human placenta with successive usage of two affinity sorbents--immobilized monoclonal antibodies to alpha v beta 3 integrin and immobilized RGD-containing decapeptide allowed to purify this integrin's partially degraded fraction, that was nevertheless able to interact with its ligand. During the incubation of partially degraded alpha v beta 3 integrin at 37 degrees C its further degradation went on. Addition of serine proteinase inhibitors: (phenylmethilsulfonyl fluoride, leupeptin and aprotinin) completely suppressed integrin further degradation of alpha v beta 3. In preparations of intact and partially degraded alpha v beta 3 integrin specific activity of two serine proteinases--urokinase and dipeptidilpeptidase IV--was discovered. alpha v beta 3 integrin, undergoing limited proteolysis, had lesser affinity towards RGD peptide, that intact integrin. The results show, that alpha v beta 3 integrin from human placenta co-purifies with serine proteinases. It is suggested that a definite part of functionally active alpha v beta 3 integrin, extracted from human placenta by triton X-100, forms a stable complex with serine proteinases. PMID- 11204625 TI - [Biochemical and genetic diagnosis of Gaucher disease and its phenotypical heterogeneity]. AB - A biochemical study of three patients with clinical symptoms of Gaucher disease was carried out. Two of them had a significant deficiency of beta glucocerebrosidase activity (a primary enzyme defect) in leukocytes and an enormous increasing of chitotriosidase activity in blood plasma that confirmed the diagnosis of Gaucher disease. Some differences in stability of mutant enzymes were found in these two cases. Mutation analysis revealed two point mutations- N370S and L444P in beta-glucocerebrosidase gene of both patients. Correlation between clinical picture, peculiarities of enzymatic defect and genetic status of patients is discussed. The influence of some epigenetic factors on phenotypic manifestation of the disease is supposed. PMID- 11204626 TI - [Metabolism of catecholamines in children with attention deficit syndrome with hyperactivity]. AB - The aim of research was to study catecholamine excretion peculiarities of the children with attention deficit hyperactivity disorder (ADHD). 25 children at the age of 7-9 years took part in this research. High-pressure liquid chromatography (HPLC) was used for measuring the content of catecholamine. The content of catecholamine was defined in the morning samples of urine. The examination showed, that ADHD children had the basal level of epinephrine and norepinephrine more than the normal control in 3.9 and 5.4 times. After cognitive tests the content of norepinephrine reduced in the ADHD group in 2.1 times in the comparison with normal control. On the contrary content of epinephrine increased in 2.8 times. CONCLUSION: Simpatico-adrenal system hyperactivity (especially it's adrenals component) characterized ADHD children. PMID- 11204627 TI - [Prediction of binding affinities of protein-ligand complexes using nonlinear models]. AB - A network model for prediction of the free energy changes in protein-ligand complexes has been developed. The 150 complexes of different nature were used as a training set. The computational physics-chemical parameters of these complexes were used as independent variables. Both classical models of multiple linear regression and several network models with one hidden layer were created and the best was chosen. Significant improvement was shown for network model prediction quality in comparison with classical model of multiple linear regression (R2 on training--0.81 and 0.54; R2 on "leave-one-out" procedure--0.74 and 0.52 respectively). PMID- 11204628 TI - [Comprehensive system of rehabilitation of handicapped children with movement disorders]. AB - A procedure is proposed for comprehensive rehabilitation of children with mental and somatic abnormalities. The rehabilitation programme contains three sections: expert diagnostic, corrective-reparative, and professional orientational ones. The results of testing the procedure in health care facilities are given. PMID- 11204630 TI - [Use of computerized psychodiagnostic methods for occupational orientation of adolescents with scoliosis]. AB - The paper deals with the characteristic features and problems of professional self-determination in adolescents with scoliosis, studied by using computer and project psychological methods. A complex of methods revealed the following psychological characteristics in the adolescents of the study group: emotional and-motivational direction, adequacy of job choice, mental tension, self assessment, possible pain symptoms in neurotic disorders. PMID- 11204629 TI - [Comprehensive assessment of psychophysiologic parameters in drug addicts as a method of necessary individualization of therapeutic measures]. AB - In Russia, the basic trends in the development of narcology are represented mainly by three lines of studies: biological, clinical, and sociopsychological ones. The use of currently available methods and techniques for analyzing motor activity, facial expression, speech makes it possible to rather clearly stratify the contingents of patients, especially in the context of adequate application of therapeutical regimens and approaches. PMID- 11204631 TI - [Diagnosis of mental retardation in children by the reaction time recording method]. AB - The paper deals with the use computer-aided recording the time of visual and motor responses to estimate the severity of mental retardation (MR) in children. It presents standard temporary indices of simple and two differential responses and data on children with MR, obtained by an original computer procedure. In mentally retarded children, the time of responses has been shown to significantly differ from the standard values; the children make more mistakes in differentiation. The children with MR of cerebral organic genesis were found to fall behind in forming differential responses to a greater extent whereas those with MR of polygenic etiology did in forming both simple and differential responses equally. PMID- 11204632 TI - [Analysis of psychomotor activity in children with spastic infantile cerebral palsy by using the computer-assisted test system "Rhythmotest"]. AB - The paper considers how to obtain quantitative characteristics of sensomotor responses while tracing, learning, and reproducing rhythmical stimuli of different frequency and modality which can be used to assess psychomotor activity, perception, attention, short-term memory in schoolchildren with infantile cerebral paralysis. The results of examinations of children with this condition are given and analyzed. PMID- 11204633 TI - [Features of spectral structure of tremor in children 5-6 years of age in health and in some neuromuscular diseases]. AB - The paper shows the informative value of a tremor signal to detect abnormalities in the formation of the neuromuscular system. Recording of the tremor signal was made with a piezoaccelerometric transducer, followed by its spectral analysis. The results of examinations of healthy children and children with various abnormalities were presented and discussed. The paper shows it possible to use spectral analysis of tremor in the development of treatment policy for children with congenital talipes. PMID- 11204634 TI - [Health-promoting technologies of the 21st century: realities and prospects]. AB - The paper outlines present-day progress and prospects of new-generation health promoting technologies by automatic control over physical condition and by drawing up individual health-promoting physical exercises and elaborating a basically new approach to evaluating the physical condition of each specific human being with regard to the naturally different qualities of individuals in the population. The authors propose a family of computer-aided diagnostically recommended expert systems which provide not only new possibilities of improving physical education, but can be used in solving other tasks of health-promotion. PMID- 11204635 TI - [Mental health of children and adolescents and present-day tasks of organizing specialized mental care]. AB - The paper analyzes the characteristics of the mental health status of children and adolescents by taking into account drug abuse and mental health in schoolchildren. The specific features of care delivered to children with intellectual impairments are considered. PMID- 11204636 TI - [Assessment of learning capacity by electroencephalographic parameters]. AB - Problems in the objective assessment of intellectual endowments are considered. In the authors' opinion, electroencephalographic (EEG) parameters are one of their measures. An examination of about 300 schoolchildren revealed signs of a correlation of EEG parameters with study progress. The methods and results of the examination are presented. PMID- 11204637 TI - [Methodological problems in the use of information technologies in physical education]. AB - The paper considers methodological problems in the use of computer technologies in physical education by applying diagnostic and consulting systems, educational and educational-and-training process automation systems, and control and self control programmes for athletes and others. PMID- 11204638 TI - [Use of a bilateral stabilographic platform in the diagnosis and rehabilitation of movement disorders at the clinic of nervous system diseases]. AB - The paper presents the results of the study whose aims were to reveal the specific features of vertical posture maintenance in patients with various motor disorders by using a computer stabilographic complex with a bilateral platform, to draw up computer rehabilitative programmes that take into account the detected features of posture stability disorders in these groups of patients, to evaluate the efficiency of use of programmes drawn up to train vertical posture stability in the rehabilitation of patients with motor disorders of various origin. PMID- 11204639 TI - [Use of computer test systems in the study of age-specific features of higher brain dysfunctions]. AB - The paper covers the results of the study whose aim was to determine the quantitative and structural features of neurological and neuropsychological disorders in elderly patients with normotensive hydrocephalus and dyscirculatory encephalopathy from neuropsychological findings and by means of computer test systems. PMID- 11204640 TI - [Dynamics of child's cognitive development in transition to schooling]. AB - Intensive maturation of arbitrary attention occurs in the making of higher mental functions in children in transition to schooling. The study has yielded standard indices of changes in some higher mental functions at the age of 6-8 years, which makes it possible to make a timely objective diagnosis in mental and neurological practice to predict the child's development, and to provide a required complex of medical and pedagogical corrective measures. PMID- 11204641 TI - [Computer-assisted stabilometric, diagnostic and rehabilitating complex "Stabilotest"]. AB - Study of the movement of the human body gravity center projection to the horizontal plane (the stabilometric method) is widely used in neurologic, orthopedic, mental, physiological, and other studies. The paper reflects principles in construction and examples of using the stabilometric method as a software package intended for the diagnosis and rehabilitation of motor dysfunctions in regulating the vertical posture in practical medicine and researches. PMID- 11204642 TI - [Radiotherapy: metrological provision]. AB - The accuracy of delivering the dose of radiation during the therapy is determined by many factors. Its enhancement requires substantial material costs. All the requirements for enhancing the accuracy are shown to be outrageous as the proportion of negative results of treatment virtually does not vary with the dosimetric and technical equipping of radiation therapy. This must alter its technical equipping policy without increasing the requirements for the accuracy of dosimetric measurements. PMID- 11204643 TI - [Current informational technologies in the structure of medical and psychological tasks of school education]. AB - Prospects for equipment of present-day school with computing machinery allow fresh approaches to be applied to the improvement of means for diagnosis and health prophylaxis in children and to professional orientation. Automatic systems have been developed for diagnosing diseases and monitoring the sociomental health of children and the adaptation of junior and middle schoolchildren to school activities. The systems provide a real way of successfully following the development of major mental functions for prenosological diagnosis of detected abnormalities and their subsequent correction. An automatic system for professional orientation of middle- and senior-form pupils has been devised on the basis of mental diagnostic testing of the schoolchildren's professional orientation, interests, inclinations, psychophysiological and personality traits. PMID- 11204644 TI - [The smooth endoplasmic reticulum develops in mesophyll cells of early-spring ephemerals]. AB - A study was made of the mesophyll cell ultrastructure of early-spring ephemerals Scilla sibirica, Crocus vernus, Galanthus caucasicus, G. plicatus, Leucojum vernum, Muscari szovitsianum, Ornithogalum balansae of summer-vegetating. Scilla scilloides and of S. sibirica growing in greenhouse. The highly developed smooth endoplasmic reticulum (SER) was a distinctive feature of the early-spring ephemeral mesophyll cell during leaf growth (cell expansion). Direct connections of SER-compartments with the tonoplast were found (SER and vacuole cavities were continuous). On running through the cytosol the SER tubules were in close contact with the plasma membrane. SER was not found during the same period of cell expansion in summer-vegetating Scilla scilloides and S. sibirica growing in greenhouse, as well as in mature cells of all investigated plants. The role of SER in the adaptation of early-spring ephemerals to drastic temperature fluctuations is discussed. PMID- 11204645 TI - [Reorganization of the chloroplast thylakoid system during decay of acquired thermotolerance of photosynthesis and aging of wheat leaves]. AB - A 3 hours heating at 39 degrees C of 14-day old wheat plants increases the termotolerance of photosynthesis, and also the length and number of thylakoids in chloroplast in mature leaves. The acquired termotolerance disappears within 10 days. Simultaneously the intensity of photosynthesis and the length of thylakoids decrease. Reduction of photosynthesis ability and of thylakoid membranes occurs in the first leaves of non-hardened plants during 14-29 days after sowing. The intensity of photosynthesis in plants of both variants positively correlates with the length of grana membranes and with the total length of membranes of all thylakoids. Besides, a positive correlation was detected between the intensity of photosynthesis and the share of small (2-7 thylakoids) grana and the length of their membranes in non-hardened plants. The level of thermotolerance of photosynthesis in leaves in heat hardened plants correlates positively with the length of grana membranes and with the total length of all thylakoid membranes and the share of small grana. PMID- 11204646 TI - [Ultrastructure of bacteroid-containing tissue of Pisum sativum L. peas having various regulatory mechanisms of nodulation]. AB - The infected root nodule cells of Pisum sativum cvs. Torsdag, Rondo and its supernodulating mutant nod3 have been investigated by transmission electron microscopy and morphometrically. Torsdag and nod3 developed effective nodules, when grown with or without nitrates in the growth medium. The nodules developed by Rondo were ineffective in the presence of nitrates, and otherwise effective. An obvious similarity in the fine structure of bacteroid tissue of root nodules has been observed in Torgsdag (Nod5) and the supernodulating mutant nod3, both forms being nitrate-tolerant, but nodulation being controlled by different genetic systems. The statistical processing results showed significant differences in the respective morphometric parameters of nodule cells between the plants grown according to either scheme: with and without nitrates. Combined nitrogen is likely to affect the ratio of symbionts in the infected nodule cells of cultivars with nitrate-tolerant nodulation. PMID- 11204648 TI - [Rodlet cells of fish in calcium deficiency in the external environment]. AB - The ultrastructure of rodlet cells from the heat kidney of the carp Cyprinus carpio L. and tilapia Oreochromis mossambicus Peters has been studied. All the investigated cells displayed a common structure. The number of rodlet cells increased after exposure of fishes in Ca(2+)-free water or in the water supplemented with NH4+ or Cd2+. The latter were found to suppress Ca(2+) absorption from the environment. PMID- 11204647 TI - [Cajal bodies in nuclei of oocytes from the scorpion fly Panorpa communis]. AB - The absence of nucleoli and rRNA synthesis in oocyte nuclei of the scorpion fly, Panorpa communis, was demonstrated using hybridization in situ. The immunocytochemical characteristics of a single large nuclear body of P. communis oocytes has been done which enabled us to recognize this structure as a Cajal body (CB). A marker of CBs coilin was detected in CBs of P. communis oocytes in addition to Sm-epitope of small nuclear RNPs (snRNPs), trimethylguanosine cap of snRNAs, and non-snRNP splicing factor, SC35. Besides, inactive hyperphosphorylated and nonphosphorylated forms of RNA polymerase II were also found in CBs. We put forward a suposition on possible roles of CBs in P. communis oocytes. On the one hand, CBs take part in the storage of RNA transcription and processing components to be used later during embryogenesis. On the other hand, they provide the primary assembly and redistribution of pre-mRNA transcription and processing components of the oocyte itself. PMID- 11204649 TI - [Induction of apoptosis in murine myeloma cells NS0/1, transfected with the gene for the basic heat shock protein HSP70i]. AB - Murine myelomas are rare cell variants deficient in inducible isoform of Hsp70 that protects cells from injury. In these cells Hsp70 is absent and is not induced under stress conditions. In this study myeloma cells NS0/1 were transfected with hsp70, and their susceptibility to apoptosis was challenged by serum deprivation or hydrogen peroxide. Expression of Hsp70 in NS0/1 cells made them more resistant to apoptosis in serum-free medium but did not affect their response to hydrogen peroxide. Hsp70 involvement in the protection of myeloma cells from apoptosis caused by different agents is discussed. PMID- 11204650 TI - [Noninduced single-stranded breaks in DNA in murine F9 teratocarcinoma cells]. AB - Our previous study demonstrated the high incidence of non-induced DNA single strand breaks (SSB) in preimplantation mouse embryo genom (Patkin et al., 1994). F9 mouse teratocarcinoma cell line is an in vitro model for early embryonal differentiation, since F9 cells remind in many respects the inner cell mass cells of mouse blastocyst and are capable of differentiation under retinoic acid (RA) and dibutyryl cAMP (db-cAMP) treatment. Using gap filling reaction of F9 metaphase chromosomes and single-cell DNA electrophoresis, we have observed multiple SSB in undifferentiated F9 cells as well as in F9 cells at the early steps of RA-induced differentiation (days of RA treatment), but not in terminally differentiated F9 cells and in mouse embryonal fibroblasts. Rad51 nuclear protein that binds specifically single stranded DNA is highly expressed in all cells of undifferentiated F9 population and is not expressed in terminally differentiated F9 population. Multiple SSB could lead to enhanced rate of sister chromatid exchanges (SCE) in F9 cells. In undifferentiated F9 population the level of SCE was 9.6 +/- 0.44 per metaphase, that was not higher than in NIH 3T3 cell line. However, RA treatment for 48 h led to rising the SCE level up to 16.68 +/- 0.72 followed by its decrease to the initial rate by 72 h of RA treatment. Since the enhanced level of SSB in undifferentiated F9 cells and in mouse blastocyst does not normally lead to chromosomal instability, we consider SSB to be a natural consequence of fast-going DNA replication in these cells. PMID- 11204651 TI - [Effect of the C-terminal actin-binding sites of caldesmon on the interaction of actin with myosin]. AB - TRITC-phalloidin or FITC-labeled F-actin of ghost muscle fibers was bound to tropomyosin and C-terminal recombinant fragments of caldesmon CaDH1 (residues 506 793) or CaDH2 (residues 683-767). After that the fibers were decorated with myosin subfragment 1. In the absence of caldesmon fragments, subfragment 1 interaction with F-actin caused changes in parameters of polarized fluorescence, that were typical of "strong" binding of myosin heads to F-actin and of the "switched on" conformational state of actin. CaDH1 inhibited, whereas CaDH2 activated the effect of subfragment 1. It is suggested that C-terminal part of caldesmon may modulate the transition of F-actin subunits from the "switched on" to the "switched off" state. PMID- 11204652 TI - [Features of formation of phases of dual-phase polymeric system in the presence of collagen I, laminin I, and their mixtures]. AB - A study was made of the phase formation kinetics of a two-phase aqueous polymer system, consisting of 7.8% (w/w) dextran-500 and 4.6% (w/w) polyethylene glycol 6000, in the presence of various concentrations of collagen (0.07-0.20 mg/ml), laminin I (0.01-0.03 mg/ml) and their mixture. The phase formation was evaluated by registration of its optical density on a spectrophotometer. The obtained two phase polymer system optical density curves and also the partitioning coefficients for the studied objects depend on surface properties of these objects. It has been shown that the surface properties of collagen I and laminin I differ according to differences in their molecules conformations, and that the phase formation kinetics points to their interaction during a mutual partitioning of these proteins in the system. The authors made a conclusion that collagen I and laminin I in the two-phase polymer system conditions could make complexes. PMID- 11204654 TI - [Effect of certain lectins on platelet aggregation in healthy people]. AB - A study was made of the ability of some plant lectins, which bind specifically to different carbohydrate determinants of glycoproteins, to induce the platelet aggregation in healthy humans. It has been shown that phytohemagglutinin (PHA) and wheat germ agglutinin (MGA) induce a more marked platelet aggregation than concanvalin A (Con A). Lens culinaris agglutinin (LCA) had a slight aggregate activity. It was pointed at different roles played by carbohydrate determinants of platelet glycoproteins in fulfilling their aggregation function. PMID- 11204655 TI - [Internuclear chromosomal bridges and nuclei with protrusions in cellular populations of rat PA-23 rhabdomyosarcoma]. AB - Internuclear chromosome bridges (CB) and nuclear protrusions (NP) were investigated in cell populations of RA-23 rat rhabdomyosarcoma. A morphological classification of different types of CB and NP has been offered. The obtained data suggest a morphological similarity between CB and NP. It is likely that NP could arise from CB after its break. So, NPs may be regarded as remains of broken CB. PMID- 11204653 TI - [External signals can induce stable increase in frequency of cell death in populations]. AB - Relatively weak radiation and some other external actions, producing no "forced" cell death, trigger some intracellular mechanisms in various unicellular organisms (amoebae, ciliates, yeasts) and in the studied mammalian cells (rat vascular endotheliocytes). These mechanisms provide spasmodic changes: massive transition of cell populations into a stationary alternative state which is characterized by an increased predisposition to cell death, in comparison with the initial level. This phenomenon is considered as a particular, widely spread in nature form of genetic control of cell death frequency populations. PMID- 11204656 TI - [Mode of serotype inheritance in exoconjugant progeny of the ciliate Dileptus anser]. AB - Two clones of Dileptus anser, originally isolated from natural reservoirs and referred to below as B and D clones, were found to display different serotypes, when cultured under identical laboratory conditions. On being tested with two different polyclonal rabbit immune sera against each particular clone (the classic immobilization test) these clones showed no cross-reaction. At a standard dilution (1:50) and at a standard exposure time (4 h), either of the two immune sera immobilized 100% or commonly 0% of homologous and heterologous clone cells, respectively. In addition, the difference in serotypes was confirmed by the immunofluorescence analysis. By crossing (conjugation) between B (mating type I) and D (mating type III) cells, exconjugant F1 clones were obtained. Their serotypes were then tested (the same immobilization test) with antisera against both the "parental" clones: some clones were tested before their sexual maturation in ca. one month after conjugation, while others were examined in approximately 4 months after conjugation, i.e. after reaching maturity. Each of the F1 clones could react with both immune sera, which means that they possessed the intermediate, "hybrid" phenotype. Five different F1 clones were selected, and each of them was back-crossed to both "parental" clones, B and D. We succeeded in raising 25 exconjugant F2 (B1, to be more exact) clones from F1 x B crosses and 26 clones from F1 x D crosses. The conventional testing of these clones in 5-10 weeks after conjugation provided quite unexpected results, since among them no segregation for "parental" serotypes was observed. Each of the 51 tested clones demonstrated the "hybrid" serotype--seemingly the same as that of F1 clones. Such a non-Mendelian inheritance of the character is hardly to explain from the standard, canonical assumptions on the genetic control of serotype difference between original "parental" clones (different alleles in one locus? different loci?). Also it does not seem likely that the absence of segregation could result from differential survival of various phenotypes in F2 (although the total viability of exconjugant clones appeared rather low). The above data obviously need further confirmations and experimental analyses. We attempt to discuss the obtained results in terms of the epigene hypothesis (Tchuraev, 1975) and in relation to the epigenetic control of serotype expression in species of the Paramecium aurelia complex and in Tetrahymena thermophila, which are "the chosen few" subjects in ciliate genetics. PMID- 11204657 TI - Safety of oxaliplatin in the treatment of colorectal cancer. AB - The new platinum compound oxaliplatin (Eloxatin) appears to have activity, either alone or in combination, as both first- and second-line therapy for advanced colorectal cancer. Unlike other platinum derivatives, it is not associated with significant nephrotoxicity or ototoxicity. The addition of oxaliplatin at 85 mg/m2 to a fluorouracil/leucovorin-based regimen administered every 2 weeks is well tolerated. The incidence of diarrhea and stomatitis increases with the addition of oxaliplatin, but can be managed by adjusting the dose. There is also a significantly higher incidence of grade 3 or 4 neutropenia with oxaliplatin. Neutropenic febrile complications are rare. The occurrence of other hematologic, hepatic, or renal toxicities does not increase when oxaliplatin is added to fluorouracil-based regimens. Unlike other agents used for the treatment of colorectal cancer, oxaliplatin causes acute and chronic neurosensory symptoms. These acute symptoms are managed by taking precautions (e.g., avoid cold drinks/food for a few days following treatment). Cumulative neurotoxicity is the dose-limiting toxicity associated with oxaliplatin treatment. This toxicity appears reversible with discontinuation of the drug and typically occurs well after the onset of tumor response. PMID- 11204658 TI - Second-line therapy in colorectal cancer. AB - Second-line therapy is a relatively new concept for gastrointestinal oncologists. Although retreatment with fluorouracil (5-FU) is common, offering colorectal cancer patients a different chemotherapeutic agent as second-line therapy is a fairly recent strategy. The focus of this article is on the use and efficacy of oxaliplatin (Eloxatin) as second-line therapy for colorectal cancer. As such, this article will present very limited data on the toxicity of oxaliplatin regimens. PMID- 11204659 TI - NCI cooperative research and development agreements. AB - The Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) currently sponsors more than 160 Investigational New Drug applications (INDs), and is involved in approximately 1,600 active protocols. It is also currently involved in more than 50 collaborative agreements with pharmaceutical companies. These agreements consist of cooperative research and development agreements (CRADAs) and clinical trials agreements (CTAs). A CRADA is a detailed contract between the NCI and a pharmaceutical company for the clinical co development of an investigational agent, and may include preclinical development that stipulates terms for a broader scope of research than that covered by a CTA. The CTEP/Investigational Drug Branch is currently involved in a number of oxaliplatin (Eloxatin) protocols under the CRADA program. PMID- 11204661 TI - Oxaliplatin in tumors other than colorectal cancer. AB - Oxaliplatin (Eloxatin) has demonstrated significant activity in a variety of tumor types in addition to colorectal cancer. Several studies have reported on the effectiveness of oxaliplatin as single-agent treatment or in combination with cisplatin (Platinol) or paclitaxel (Taxol) in pretreated advanced ovarian cancer patients, with promising data reported for the combination of oxaliplatin and cisplatin as first-line therapy. Other small studies have shown the activity of single-agent oxaliplatin in anthracycline-resistant metastatic breast cancer and refractory non-Hodgkin's lymphoma. Data have also demonstrated the activity of oxaliplatin in combination with gemcitabine (Gemzar) in advanced pancreatic cancer. In recurrent germ-cell cancer, a "biplatin" regimen of oxaliplatin plus cisplatin was found to be effective salvage therapy. Data from these studies indicate that oxaliplatin is active in both platinum-resistant disease and in tumor types that have previously been unresponsive to platinum treatment. Moreover, it enhances the effect of cisplatin or carboplatin, which is a striking demonstration of differing mechanisms of action. Ongoing and planned trials will evaluate the efficacy of oxaliplatin in other disease settings and combinations. PMID- 11204660 TI - Oxaliplatin with 5-FU or as a single agent in advanced/metastatic colorectal cancer. AB - No adequate second- or third-line therapy is available in the United States for patients with metastatic colorectal cancer and disease progression following treatment with fluorouracil (5-FU)-based therapy and an irinotecan (CPT-11, Camptosar)-containing regimen, or a combination of the two. Oxaliplatin (Eloxatin), a new platinum analog, has demonstrated high activity in the treatment of colorectal cancer, especially when combined with 5-FU and leucovorin. The combination of oxaliplatin and 5-FU/leucovorin has been approved in Europe for the first- and second-line treatment of colorectal cancer. This compassionate-use study was initiated because of the unavailability of the agent in the United States and inadequate US safety data. The following review summarizes data from this ongoing study, the primary focus of which is to provide oxaliplatin for compassionate use until it receives US Food and Drug Administration approval and becomes available commercially. PMID- 11204662 TI - Rectal cancer: integrating oxaliplatin into chemoradiation studies. AB - The current standard of care for patients with stage T3 rectal cancer is adjuvant combined-modality treatment with radiation and fluorouracil (5-FU)-based chemotherapy. Although data from randomized phase III trials comparing preoperative and postoperative combined-modality therapy are lacking, preoperative therapy is an option in T3 disease and can be considered the standard of care for T4 disease. Given its effects in reducing systemic disease in stage IV rectal cancer and its potential for radiosensitization of target tumors, oxaliplatin (Eloxatin), a new cytotoxic agent from the diaminocyclohexane platinum family, is being evaluated in preoperative combined-modality regimens in a Cancer and Leukemia Group B (CALGB) phase I/II study (protocol 89901) in T4 disease and an Eastern Cooperative Group (ECOG) phase I study (E-1297) in locally advanced T3 or T4 disease. PMID- 11204663 TI - Oxaliplatin in colorectal cancer: current studies. AB - One of the more promising chemotherapeutic agents for patients with metastatic colorectal cancer is oxaliplatin (Eloxatin), a third-generation platinum derivative with a unique mechanism of action. Preclinical studies corroborated by results from early trials suggested that oxaliplatin could be particularly advantageous when used in combination with fluorouracil (5-FU)/leucovorin. In addition, early studies of oxaliplatin as monotherapy showed clear activity similar in magnitude to that observed with other active agents. When administered as neoadjuvant therapy in patients with unresectable liver metastases, the responses were substantial enough for some patients to undergo potentially curative hepatic resection. These trials also demonstrated a reasonable safety profile for oxaliplatin. In light of the accumulating data on the use of oxaliplatin in advanced colorectal cancer, the North Central Cancer Treatment Group (NCCTG) and other cooperative groups developed trials to further define the specific therapeutic roles and optimal regimens of oxaliplatin combined with 5-FU and leucovorin, as well as other agents. A number of studies are underway in the United States, including the three-arm NCCTG N9741 trial in patients with previously untreated metastatic colorectal cancer, the NCCTG N9841 trial in patients who progressed on 5-FU/leucovorin, and the National Surgical Adjuvant Breast and Bowel Project (NSABP) C-07 adjuvant trial for stage II and III colorectal cancer. PMID- 11204664 TI - Intrahepatic therapy for resected hepatic metastases from colorectal carcinoma. AB - A significant number of patients with colorectal cancer will present with hepatic metastases as their only site of metastatic disease. Surgical resection in patients with a limited number of metastases will lead to long-term survival in up to one-third. However, following surgery, many of these patients will relapse within the liver, and many will develop extrahepatic metastases. The use of hepatic artery infusion alternating with systemic therapy has proven to reduce the risk of recurrent disease and improve survival. Impressive response rates have been achieved with the combination of oxaliplatin and fluorouracil (5-FU) in patients with metastatic colorectal carcinoma. In one trial, this combination resulted in significant tumor shrinkage allowing resection of previously unresectable hepatic metastases. Given the promising activity of oxaliplatin (Eloxatin), 5-FU, and leucovorin, a trial is now in development to assess the efficacy of this combination when used together with hepatic artery infusion. PMID- 11204665 TI - Novel combinations with oxaliplatin. AB - Oxaliplatin (Eloxatin) is a novel antineoplastic platinum derivative that may exert its cytotoxic effects by blocking DNA replication/transcription, thus resulting in cell death in proliferating cells, as well as apoptosis. Oxaliplatin is often more potent than other platinums such as cisplatin (Platinol) in vitro, and shows greater efficacy in preclinical studies against many tumor cell lines, including some that are resistant to cisplatin and carboplatin (Paraplatin). Oxaliplatin is approved for use with the fluoropyrimidines in the treatment of metastatic colorectal cancer in Asia, Latin America, and Europe. In light of the broad efficacy of oxaliplatin in several solid tumors and the encouraging preclinical data on combination therapy with novel agents (e.g., thymidylate synthase inhibitors, epidermal growth factor-receptor antagonists, microtubule interactive agents), this article will review the published literature on novel combinations that have been tested in the laboratory and/or the clinic. PMID- 11204666 TI - Efficacy of oxaliplatin in the treatment of colorectal cancer. AB - Colorectal cancer is one of the leading causes of cancer death. The mainstay of chemotherapy in colorectal cancer patients for the past 40 years has been fluorouracil (5-FU). Oxaliplatin (Eloxatin) is a novel platinum compound with promising activity in colorectal cancer. As a single agent, oxaliplatin has produced response rates of 12% to 24% in patients with previously untreated advanced colorectal cancer, and 10% to 11% in patients with relapsed or refractory advanced colorectal cancer. In phase II trials, oxaliplatin combined with 5-FU, with or without leucovorin, was associated with response rates of 60% and higher when used as front-line therapy, and when used in patients with relapsed or refractory advanced colorectal cancer, response rates ranged from 25% to 50%. In the front-line setting, two randomized trials of 5-FU and leucovorin, with or without oxaliplatin, demonstrated that the addition of oxaliplatin significantly increases response rate and time to tumor progression, but not survival, over 5-FU plus leucovorin alone. The reasons for this discrepancy are unclear, and several possibilities are being considered. Additional phase III trials are underway to clarify the contribution of oxaliplatin in the treatment of patients with locally advanced and metastatic colorectal cancer. PMID- 11204668 TI - Thalidomide in solid tumors: the London experience. AB - Investigators at the Royal Marsden Hospital and University College in London have studied thalidomide (Thalomid) as both low-dose (100 mg orally, every night) and high-dose (600 mg, given as 300 mg twice per day) therapy for patients with a variety of solid tumors. In the phase II low-dose study, responses were disappointing in patients with melanoma, ovarian cancer, and breast cancer. Results for patients with renal-cell carcinoma were more encouraging. A case study of a patient with metastatic renal-cell carcinoma in the lung and lymph nodes in the low-dose thalidomide study illustrates that (1) responses may be very slow; (2) the palliative response is separate from the overall response, occurs much earlier, and is not consistent with an antiangiogenic action; and (3) peripheral neuropathy is a manageable side effect. Besides peripheral neuropathy, patients can experience severe constipation (even on low doses) as well as headache, edema, and skin rash for which treatment recommendations can be made. Anecdotal benefits of thalidomide include enhanced or maintained appetite, improved sleeping, and reduced sweating. The high-dose study has been submitted for publication. PMID- 11204667 TI - Thalidomide in multiple myeloma. AB - Recent evidence suggests that angiogenesis is increased in multiple myeloma and has prognostic value in the disease. Based on the increased angiogenesis observed in myeloma, thalidomide (Thalomid) has been studied as antiangiogenic therapy. Although its mechanism of action in myeloma is unclear, several trials show that thalidomide is active in 25% to 35% of patients with relapsed myeloma. Since many patients who respond have failed other active regimens, including transplantation, these results are impressive. Major toxicities include constipation, sedation, skin rash, fatigue, and peripheral neuropathy. Studies are ongoing to determine its role as initial treatment for myeloma. Trials are also underway combining thalidomide with other active agents. This article summarizes the current status of thalidomide therapy in myeloma. PMID- 11204669 TI - Development of angiogenesis inhibition as therapy for prostate cancer. AB - Angiogenesis is essential to prostate cancer progression. The first study of antiangiogenic therapy in patients with locally advanced prostate cancer at The University of Texas M. D. Anderson Cancer Center showed that preoperative treatment with a fumagillin analog was safe. Microvascular density correlated with Gleason score, but marked intertumoral and intratumoral changes were observed. Clinical experience with thalidomide (Thalomid), which inhibits angiogenesis induced by both vascular endothelial growth factor and basic fibroblast growth factor, has included observation of "clinical improvement" in patients with androgen-independent prostate cancer and anecdotal responses in patients with metastatic disease refractory to chemotherapy. In an effort to assess the in vivo effect of thalidomide in prostate carcinoma, we have initiated a study of neoadjuvant thalidomide treatment in patients with locally advanced prostate cancer that is to include serial ultrasonographic and pathologic evaluation, as well as serial collection of serum/urine markers that may prove useful surrogate markers of antiangiogenic activity. We have also initiated a phase I/II trial of thalidomide, paclitaxel (Taxol), and estramustine (Emcyt) in patients with metastatic androgen-independent prostate cancer progressing after up to two courses of chemotherapy. PMID- 11204670 TI - New approaches in the treatment of metastatic melanoma: thalidomide and temozolomide. AB - Although melanoma is a relatively chemoresistant malignancy, systemic chemotherapy remains the primary treatment for metastatic melanoma. The observation of vasculogenic mimicry in aggressive melanoma has prompted investigation into using an antiangiogenic agent to enhance the antitumor activity of chemotherapy in metastatic melanoma. Thalidomide (Thalomid) exhibits antiangiogenic activity and other biological modulatory effects that may provide additive or synergistic antitumor effects when given concurrently with chemotherapy. A phase I/II study of thalidomide and temozolomide in the treatment of metastatic melanoma is in progress. Preliminary results of this combination therapy have shown significant antitumor activity, including some striking responses in brain metastases. PMID- 11204671 TI - Irinotecan and thalidomide in metastatic colorectal cancer. AB - Fifteen patients with metastatic colorectal cancer were treated with irinotecan (CPT-11, Camptosar) at 300 to 350 mg/m2 every 21 days and thalidomide (Thalomid) at 400 mg/d. Of the 15 patients, 11 were in a pilot study and 4 were in an ongoing phase II protocol. There were 12 men and 3 women, with a median age of 56 years (range: 29 to 79 years). Patients were treated with a median of three cycles (range: one to eight cycles). The four patients enrolled in the formal protocol were not evaluable for response at the time of this report. Of the 11 patients in the pilot study, 10 were evaluable for response; there were two complete responses, two partial responses, and six progressions. Investigators noted a remarkable absence of grade 3/4 gastrointestinal toxicities, and concluded that further testing of the complete response and toxicity profile of the irinotecan/thalidomide regimen was warranted. PMID- 11204672 TI - Thalidomide for recurrent renal-cell cancer in a 40-year-old man. AB - A pilot study was performed at The University of Texas M. D. Anderson Cancer Center to determine the feasibility of using thalidomide in a population of renal cell carcinoma patients who had progressive disease despite chemotherapy and immunotherapy. Metastatic renal-cell carcinoma patients with adequate oral function were entered onto a study after signing an internal review board approved informed consent. There were no exclusion criteria for prior therapy. Nineteen previously treated patients and one untreated patient with progressive renal-cell carcinoma received oral thalidomide as a single agent. The starting dose was 200 mg and the dose was increased by 100 to 200 mg every week until it reached 1,200 mg/d. Response was assessed on the basis of a radiographic reduction of the metastatic sites involved. A case report describing one of the patients involved in the pilot trial is included. PMID- 11204674 TI - Factors related to relapse after Le Fort I maxillary advancement osteotomy in patients with cleft lip and palate. AB - OBJECTIVE: To identify factors associated with relapse after maxillary advancement in cleft lip and palate patient. SUBJECTS: Seventy-one cleft lip and palate patients underwent Le Fort I maxillary advancement osteotomy between 1988 and 1998, and 58 patients (42 unilateral cleft and 16 bilateral cleft) with complete data were investigated for relapse by clinical and cephalometric analysis. The clinical follow-up period ranged from 1.5 to 8.5 years (mean 2.5 years). RESULTS: Horizontal advancement averaged 6.9 mm. There was a significant correlation between surgical movement and postoperative relapse in both the horizontal and vertical planes. In vertical repositioning, 15 patients had maxillary intrusion and 31 had inferior repositioning. There was a significant difference between the intrusion group and the inferior repositioning group. There was a significant correlation between surgical and postoperative rotation regardless of the direction. Other factors were evaluated by the horizontal relapse rate. Type of cleft and the rate of relapse were statistically associated. A relapse was more likely to occur in patients with bilateral cleft. There were no significant associations with the rate of relapse in type of operations or previous alveolar bone grafting. There was no significant correlation between the rate of relapse and the number of missing anterior teeth, postoperative overbite and overjet, and age at operation. Four of 71 patients experienced major relapse, and 3 of them underwent jaw surgery again. CONCLUSIONS: Based on clinical and cephalometric analysis, two-jaw surgery should be performed in cases of severe maxillary hypoplasia, and overcorrection may be useful in inferior repositioning or surgical rotation. Special attention should be paid to the patient with bilateral cleft, multiple missing teeth, or shallow postoperative overbite. PMID- 11204675 TI - Secondary bone grafting of alveolar clefts: a densitometric comparison of iliac crest and tibial bone grafts. AB - OBJECTIVE: To evaluate changes in the optical density of secondary alveolar cleft bone grafts obtained from two different donor sites over time and to determine whether one donor site gives a higher recipient bone density than the other. METHODS: A prospective study was performed evaluating 40 healthy patients with congenital cleft lip and palate undergoing secondary alveolar bone grafting, 20 (14 boys and 6 girls) having iliac crest and 20 (12 boys and 8 girls) receiving tibial bone grafts. Bone harvest and grafting was carried out by one operator (G.P.). Optical density of iliac and tibial grafts measured using a computerized densitometer, was compared at 6 days, 6 weeks, and 3 months. Due to interference from orthodontic appliances, optical density measurements for 16 subjects were not possible, and these patients were excluded from the study. The length of hospital stay postoperatively for both grafting procedures were recorded. RESULTS: A significant decrease in relative bone density was demonstrated during the 3-month postoperative period in both iliac and tibial bone graft groups (p < .05). The difference in densities between iliac crest and tibial groups were not significantly different at any of the time points (paired t test, p > .05). Subjects undergoing iliac crest grafts stayed an average of 5 days in the hospital postoperatively, compared with subjects with tibial grafts who stayed an average of 3 days postoperatively. CONCLUSION: Optical density measurements of bone grafted into alveolar clefts, reported here for the first time, provide a valuable objective assessment of graft progress. Tibial and iliac crest grafts gave similar optical densities at recipient sites over the first 3 months. Iliac crest grafts required significantly longer postoperative stay; an important consideration in selecting donor sites for secondary bone grafting. PMID- 11204676 TI - Hypodontia in hemifacial microsomia. AB - OBJECTIVE: The purpose of this study was twofold: (1) to describe the patterns of missing teeth in patients with hemifacial microsomia (HFM) and (2) to compare the prevalence of missing teeth in subjects with HFM with a group of unaffected subjects. STUDY DESIGN: A descriptive study was conducted comparing HFM subjects with a group of patients selected from an orthodontic clinic. METHODS: The prevalence of missing teeth was assessed by evaluation of panoramic radiographs. At the time of the study, records of 125 patients with HFM were available from the Craniofacial Center at Boston's Children's Hospital. Seventy-six met inclusion criteria for radiographic analysis of hypodontia. Fifty-two patients met inclusion criteria into the comparison study in which the prevalence of hypodontia was compared with a group of patients from the Department of Orthodontics at Harvard School of Dental Medicine. A Fisher's exact test was conducted to test the hypothesis that HFM patients have a greater prevalence of missing teeth than individuals without the anomaly. A chi-square test for trend was conducted to determine whether hypodontia was more prevalent with increasing severity of the mandibular deformity in HFM. RESULTS: Hypodontia was more common among HFM patients (26.9%) versus the comparison group in which no missing teeth were recorded (p < .0001). Additionally, the degree of hypodontia was correlated with the grade of mandibular hypoplasia (p = .024). CONCLUSION: Hypodontia was found to be more prevalent in patients with HFM than in comparison subjects, possibly indicating an etiologic link between the two conditions. PMID- 11204677 TI - Cleft lip and palate care in the United Kingdom--the Clinical Standards Advisory Group (CSAG) Study. Part 1: background and methodology. AB - OBJECTIVE: To review the history of cleft care in the United Kingdom and the rationale and methodology of a national study. DESIGN: Descriptive overview to introduce this series of papers. SETTING: Fifty National Health Service cleft teams. PATIENTS/PARTICIPANTS: Two age cohorts, 5-year-olds and 12-year-olds, with nonsyndromic complete unilateral cleft lip and palate and their parents. MAIN OUTCOME MEASURES: Facial development and appearance, quality of bone grafts, speech, oral health and patient/parent satisfaction. CONCLUSIONS: The case for a national assessment of cleft care is made. The methodology of the cross-sectional outcome study is described, together with a survey of training for recently appointed clinicians. PMID- 11204678 TI - Cleft lip and palate care in the United Kingdom--the Clinical Standards Advisory Group (CSAG) Study. Part 2: dentofacial outcomes and patient satisfaction. AB - OBJECTIVE: To describe facial development and appearance, quality of bone grafts, oral health, and patient/parent satisfaction, with clinical outcome, for children in two age cohorts born with unilateral cleft lip and palate (UCLP) throughout the United Kingdom. DESIGN: Cross-sectional outcome study. SETTING: Fifty National Health Service cleft centers. PARTICIPANTS: Children born with complete UCLP between April 1, 1982, and March 31, 1984, (12-year-olds) and April 1, 1989, and March 31, 1991 (5-year-olds). Data were collected for 239 5-year-olds and 218 12-year-olds. The parents of these children were also interviewed to determine levels of satisfaction with care received. MAIN OUTCOME MEASURES: Skeletal pattern, dental arch relationship, success of alveolar bone grafting, facial appearance, oral health status, and patient/parent satisfaction. RESULTS: Nearly 40% of 5- and 12-year-olds had poor dental arch relations, and 70% of 12-year olds had midface retrusion. Fifteen percent of 12-year-olds had not received an alveolar bone graft, and only 58% of bone grafts that had been undertaken were successful. Twenty percent of 12-year-olds and 40% of 5-year-olds had untreated dental caries. Less than one-third of subjects had a good facial appearance as judged by a panel of experts. Levels of patient and parent satisfaction were generally high. CONCLUSION: A rigorous evaluation of cleft care in the United Kingdom reveals disappointing outcomes. PMID- 11204679 TI - Cleft lip and palate care in the United Kingdom--the Clinical Standards Advisory Group (CSAG) Study. Part 3: speech outcomes. AB - OBJECTIVE: To summarize speech outcomes in children born with unilateral cleft lip and palate (UCLP) throughout the United Kingdom. DESIGN: Prospective descriptive study on a cross-sectional sample of children. PATIENTS/PARTICIPANTS: Data were collected for 238 5-year-olds (born between April 1, 1989, and March 31, 1991) and 218 12-year-olds (born between April 1, 1982, and March 31, 1984) with complete UCLP. MAIN OUTCOMES: Ratings of intelligibility, nasality, "speech cleft type characteristics" and speech therapy intervention. CONCLUSIONS: Nineteen percent of 5-year-olds and 4% of 12-year-olds were judged to be impossible to understand or just intelligible to strangers. Thirty-four percent of 5-year-olds and 17% of 12-year-olds had at least one serious error of consonant production. Eighteen percent of 5-year-olds and 12-year-olds had consistent hypernasality of mild, moderate, or severe degree. Approximately two thirds of both age groups had undergone speech therapy. PMID- 11204680 TI - Cleft lip and palate care in the United Kingdom--the Clinical Standards Advisory Group (CSAG) Study. Part 4: outcome comparisons, training, and conclusions. AB - OBJECTIVE: A critical appraisal of cleft care in the United Kingdom. DESIGN: Retrospective comparative study. SETTING: All National Health Service cleft centers in the United Kingdom. PATIENTS/PARTICIPANTS: Children born with unilateral complete clefts of the lip and palate between April 1, 1982, and March 31, 1984 (12-year-olds), and April 1, 1989, and March 31, 1991 (5-year-olds). Newly appointed and senior cleft clinicians. MAIN OUTCOME MEASURES: Skeletal pattern, dental arch relationship, success of alveolar bone grafting, dental health, facial appearance, oral health status, patient/parent satisfaction. CONCLUSIONS: This paper highlights the poor outcomes for the fragmented cleft care in the United Kingdom, compared with European centers. There is an urgent need for a review of structure, organization, and training. PMID- 11204681 TI - Cleft lip and palate management by U.K. consultant oral and maxillofacial surgeons: a national survey. AB - OBJECTIVE: Following the report of the Clinical Standards Advisory Group (CSAG), a national survey of U.K. consultant oral and maxillofacial surgeons was performed to determine the current cleft lip and palate practice of this group prior to the implementation of proposed radical changes in the delivery of cleft services. The views of these surgeons regarding the proposed changes was also sought. DESIGN: An anonymous postal questionnaire sent to all 266 consultants in the U.K., which requested information on the practice of cleft surgery during a defined 1-year period (March 1997 through February 1998). It included the numbers and types of procedures performed, the involvement of multidisciplinary care, research and audit activity, and questions regarding the implementation of CSAG. RESULTS: One hundred ninety-one replies (72% response rate). Seventy-three surgeons were actively involved with mainly secondary cleft surgery. A varied number and range of procedures were undertaken, with most surgeons performing less than five of each procedure per year. Audit and research activity was 26%. The majority of both noncleft and cleft surgeons agreed with proposals made by CSAG (except for cleft osteotomy procedures). CONCLUSIONS: In the U.K. at present, there are many oral and maxillofacial surgeons performing mainly secondary cleft surgery; overall, the number of procedures performed by these surgeons per year is small. Intraspecialty referral is suggested to further improve patient outcome. PMID- 11204682 TI - Comparison between the palatal configurations in complete and incomplete unilateral cleft lip and palate infants under 18 months of age. AB - OBJECTIVE: The purpose of this study was to examine the three-dimensional characteristics of the palatal configurations in incomplete unilateral cleft lip and palate (UCLP) patients and to determine whether there are differences in the effect of early orthopedic treatment between complete and incomplete UCLP patients. DESIGN: Eight infants with incomplete UCLP and 12 infants with complete UCLP, selected at random, wore Hotz plates, and 8 other infants with complete UCLP did not. Palatal impressions were taken of these patients immediately after birth and at 1, 2, 3, 4 (just before cheiloplasty), 6, and 18 months of age (just before palatoplasty). Using our measuring system, the palatal casts were measured and compared three-dimensionally. RESULTS AND CONCLUSIONS: The palate of the incomplete UCLP patients measured immediately after birth, compared with complete UCLP, showed: (1) smaller posterior arch width; (2) sagittal arch length did not differ; (3) incisal point was located more mesially; (4) the gap between the alveolar arch forms of the major and minor segments was smaller; and (5) the curvature of the palatal surface forward the nasal cavity in the minor segment was less. At 18 months of age, the following characteristics could be observed: (1) the difference observed at birth in the posterior arch width between the incomplete and complete UCLP infants vanished; (2) a significant difference in the location of the incisal point was observed only between the incomplete UCLP infants and the complete UCLP infants with a Hotz plate; and (3) the curvature was less in the incomplete UCLP infants than in the complete UCLP infants. Furthermore, the morphological change of the palatal surface was less in the incomplete UCLP infants than in the complete UCLP infants. This suggested that any influence of the Hotz appliance might be less in incomplete UCLP than in complete UCLP. PMID- 11204683 TI - What information do parents of newborns with cleft lip, palate, or both want to know? AB - BACKGROUND: The unexpected birth of a baby with a cleft lip and palate (CL/P) is a shocking and traumatic experience, generating anxiety for parents as well as the attendant health care team. Parents frequently leave the hospital with many unanswered questions because health care professionals do not educate them adequately. OBJECTIVE: To determine what information these parents felt was "critical" for them during the immediate newborn period and to determine how the "informer" was perceived during these encounters. DESIGN: Retrospective, self administered questionnaire. SUBJECTS AND METHODS: Biologic parents of children with isolated CL/P aged 6 years and younger were surveyed. The questionnaire asked parents whether they remembered discussing diagnosis, prognosis, management, home care, and psychosocial issues. Parents were also asked to rank how "critical" it would have been for the "informer" to have discussed certain issues with them during this first day. RESULTS: Parents gave the highest priority to feeding and learning to identify illness in their baby; 95% wanted to be shown all normal aspects of their baby's exam, and 87% wanted to be told that the CL/P was not their fault. Usage of proper terminology to describe abnormal findings and receiving assurance that their child was not in pain were also important. Unfortunately, many parents reported that the informers did not address these issues. CONCLUSIONS: Parents of newborns with CL/P want basic information in the immediate newborn period, especially regarding feeding and recognizing illness. These data suggest that informers are not adequately discussing these issues with parents. PMID- 11204684 TI - Reliability of listener transcriptions of compensatory articulations. AB - OBJECTIVE: This study examined the ability of speech-language pathologists to transcribe compensatory articulation errors. DESIGN: Speech-language pathologists phonetically transcribed audiorecordings of 130 monosyllabic words, 70 of which contained compensatory articulations. PARTICIPANTS: The participants for this study were two groups of 10 speech-language pathologists. Group I included speech language pathologists who were experienced in evaluating children with cleft palate, and group II speech-language pathologists were not. RESULTS: Marked variability was evident across listeners, with percentages of agreement ranging from 19 to 71 (mean agreement = 41%). The experienced listeners performed significantly better on the transcription task than the inexperienced listeners, but poor interjudge agreement was evident across both groups. CONCLUSIONS: The results of this study suggest that speech-language pathologists may differ in their understanding of the auditory perceptual characteristics of compensatory articulations. The results underscore the need for increased training and standardization of transcription procedures. PMID- 11204685 TI - Different cleft conditions, facial appearance, and speech: relationship to psychological variables. AB - OBJECTIVE: The purpose of this investigation was to study the adjustment and learning characteristics of children with different types of clefts. The hypotheses were that there may be different relationships among cleft variables (speech and appearance) according to the cleft types. DESIGN: The study compared three cleft groups on behavior rating, anxiety scales, depression scales, and self-perception (analyses of variance) and examined the influence of facial and speech ratings on self-perception (multiple regression analyses). SETTING: All patients were treated at a university hospital cleft palate clinic. PATIENTS: Sixty-five children aged 8 years to 17 years were selected based on nonsyndromic cleft (unilateral cleft lip and palate [ULP], bilateral cleft lip and palate [BLP], and cleft palate only [CPO]) and no significant neurological condition or hearing loss. RESULTS: The findings indicated children with CPO showed greater problems with parent- and teacher-reported depression, anxiety, and learning related to speech than children with ULP or BLP. The later two groups showed fewer problems and a greater relationship of problem to facial appearance. The children with ULP self-reported lower levels of depression than the other two groups. CONCLUSIONS: Children with cleft show relatively good overall adjustment, but some problems appear related to speech and facial appearance. Subgroups may need to be studied separately. PMID- 11204686 TI - Oral clefts and vitamin supplementation. AB - OBJECTIVES: The evidence linking low levels of folic acid and orofacial clefting (OFC) is presently equivocal. There is stronger evidence for the role of folic acid supplementation in protection against the occurrence and recurrence of neural tube defects. The present investigation tested the hypotheses that cleft lip, cleft palate, or both are inversely associated with maternal intake of dietary and supplemental vitamins during the periconceptional period and first 4 months of pregnancy in a Brazilian population. DESIGN: A population-based, case control study of cleft lip with or without cleft palate (CL(P)) and isolated cleft palate (CP) in a Brazilian population. In structured interviews, case histories were taken from the mothers of a consecutive sample of 450 infants born with nonsyndromic OFC. RESULTS: Mothers who had children with CL(P) were less likely to have been supplemented during the periconceptional period. The statistical significance of the difference in prevalence of the use of supplements between mothers of patients and of controls was greater for the CL(P) group: p < .05 for CP and p < .001 for CL(P). Multivariate analysis confirmed this finding of a protective effect for both types of orofacial cleft. CONCLUSIONS: The use of vitamin supplements in the first 4 months of pregnancy was suggestive of a protective effect against the occurrence of CP and CL(P) in this population. The significance of an association between multivitamin supplementation and OFC and the possible role of gene/environment interaction are discussed. PMID- 11204687 TI - Furlow palatoplasty to restore velopharyngeal competence following tonsillectomy avulsion of a pharyngeal flap. AB - OBJECTIVE: We report the successful use of a Furlow palatoplasty to salvage velopharyngeal competence following iatrogenic avulsion of a pharyngeal flap that had been previously established to treat velopharyngeal insufficiency associated with a submucous cleft palate. INTERVENTION: A tonsillectomy, conducted by a surgeon unaffiliated with a cleft palate team, was used to remove enlarged tonsils that had developed after pharyngeal flap surgery and extended into the lateral ports causing nasal obstruction and hypernasality because of mechanical interference with port closure. A posttonsillectomy evaluation revealed avulsion of the pharyngeal flap, which was successfully treated using a Furlow palatoplasty. CONCLUSIONS: To our knowledge, this is the first report of iatrogenic avulsion of a pharyngeal flap caused by tonsillectomy. Based on a review of the literature and this case experience, we would conclude that tonsillectomy should not be regarded as a routine procedure in patients previously treated with a pharyngeal flap. If required, it should be performed by a skilled otolaryngologist, preferably one affiliated with a multidisciplinary cleft palate team who is familiar with pharyngoplasty surgery. Finally, our experience would suggest that the Furlow palatoplasty is sufficiently robust to be used as a secondary salvage procedure to restore velopharyngeal sufficiency following iatrogenic avulsion of a pharyngeal flap. PMID- 11204688 TI - Calf removal improves conception rates to the Ovsynch and CO-Synch protocols. AB - Beef cows (n = 473) from two locations were stratified by breed, postpartum interval, age, and AI sire and were randomly allotted to one of four treatments for synchronization of ovulation. Ovulation synchronization protocols included the Ovsynch protocol with (n = 114) or without (n = 123) 48-h calf removal from d 7 to 9 (d 0 = 1st GnRH injection) or the CO-Synch protocol with (n = 119) or without (n = 117) 48-h calf removal from d 7 to 9. The Ovsynch protocol included administration of GnRH (100 microg; i.m.) on d 0, PGF2alpha (25 mg; i.m.) on d 7, GnRH (100 microg; i.m.) on d 9, and timed insemination on d 10. The CO-Synch protocol included administration of GnRH (100 microg; i.m.) on d 0, PGF2alpha (25 mg; i.m.) on d 7, and GnRH (100 microg; i.m.) with timed insemination on d 9. Blood samples were collected from all cows on d -10 and d 0 for analysis of serum progesterone. Cows with at least one serum progesterone concentration greater than 1 ng/mL were considered to be cyclic at the time of treatment. Conception rates of cows that received the CO-Synch + calf removal, Ovsynch + calf removal, CO-Synch, or Ovsynch protocol (63, 61, 54, and 52%, respectively) were not different (P = 0.50). Conception rates were not different (P = 0.80) among CO Synch- and Ovsynch-treated cows; however, both estrual status and 48-h calf removal affected conception rates. Conception rates of cyclic cows (66%) were greater (P = 0.01) than those of anestrous cows (53%), regardless of which synchronization protocol was used. When data were pooled across synchronization protocol, conception rates of cows with 48-h calf removal (62%) were greater (P = 0.09) than conception rates of cows without calf removal (53%). The CO-Synch + calf removal protocol induces a fertile ovulation in cyclic and anestrous cows, requires handling cattle just three times, results in high conception rates from timed insemination, and should be a useful program for synchronization of ovulation in beef cows. PMID- 11204689 TI - Recombinant bovine somatotropin (rbST) increases size and proportion of fast glycolytic muscle fibers in semitendinosus muscle of creep-fed steers. AB - The objective of this study was to determine the effect of recombinant bovine somatotropin (rbST) on muscle fiber histology and histochemistry in creep-fed beef steers. Crossbred steer calves were assigned to one of two treatment groups: control (sham-injected; n = 12) or rbST-injected (0.09 mg x kg(-1) x d(-1); n = 12). Calves were injected every 14 d starting at d 28 of age until weaning at 205 d of age. Biopsies of the semitendinosus muscle were performed on d 100, and slaughter samples of semitendinosus muscle were collected for muscle fiber analyses on d 206. The rbST-treated calves had larger (P = 0.045) fast-twitch glycolytic (FG) fibers [2,564 +/- 10 vs 2,351 +/- 11 microm2 cross-sectional area, respectively] than controls. No differences (P = 0.36) between rbST-treated and control steers in cross-sectional area were detected for slow-twitch oxidative (SO) [1,192 +/- 20 vs 1,148 +/- 22 microm2, respectively] or fast twitch-oxidative-glycolytic (FOG) fibers [1,484 +/- 35 vs 1,403 +/- 38 microm2, respectively]. The percentage distribution for FOG fibers was greater for control calves than for the rbST-treated calves (38.4 vs 34.9 +/- 0.1%, respectively; P = 0.014), whereas the percentage distribution for FG fibers was greater in the rbST treated calves than for control calves (53.5 vs 48.4 +/- 0.2%, respectively; P = 0.03). The percentage distribution for SO fibers tended to be greater for the control calves than for the rbST-treated calves (13.1 vs 11.7 +/- 0.1%, respectively; P = 0.07). The percentage of FG fibers increased with age (45.4 vs 56.6 +/- 0.8%, respectively; P = 0.001), whereas the percentage distribution of SO (14.3 vs 10.5 +/- 0.5%, respectively) and FOG fibers (40.3 vs 32.9 +/- 0.7%, respectively) decreased (P = 0.001) from d 100 to d 206. The increased longissimus muscle area and dissectable lean tissue in rbST-treated calves are associated with a greater percentage of FG fibers, which possess larger cross sectional areas than the other fibers. PMID- 11204690 TI - Predicting percentage of intramuscular fat using two types of real-time ultrasound equipment. AB - In the present study, 500 steers were used to develop models for predicting the percentage of intramuscular fat (PIMF) in live beef cattle. Before slaughter, steers were scanned across the 11th and 13th ribs using Aloka 500V (AL-500) and Classic Scanner 200 (CS-200) machines. Four to five images were collected per individual steer using each machine. After slaughter, a cross-sectional slice of the longissimus muscle from the 12th rib facing was used for chemical extraction to determine actual carcass percentage of intramuscular fat (CPIMF). Texture analysis software was used by two interpreters to select a region for determination of image parameters, which included Fourier, gradient, histogram, and co-occurrence parameters. Four prediction models were developed separately for each of AL-500 and CS-200 based on images captured by the respective machines. These included models developed without transformation of CPIMF (Model I), models based on logarithmic transformation of CPIMF (Model II), ridge regression procedure (Model III), and principal component regression procedure (Model IV). Model R2 and root mean square error of AL-500 Models I, II, III, and IV were 0.72, 0.84%; 0.72, 0.85%; 0.69, 0.91%; and 0.71, 0.86%; respectively. The corresponding R2 and root mean square error values of CS-200 Models I, II, III, and IV were 0.68, 0.87%; 0.70, 0.85%; 0.64, 0.94%; and 0.65, 0.91%; respectively. Initially, AL-500 and CS-200 prediction models were validated separately on an independent data set from 71 feedlot steers. The overall mean bias, standard error of prediction, and rank correlation coefficient across the four AL-500 models were 0.42%, 0.84%, and 0.88, respectively. For the four CS-200 models, the corresponding overall mean values were 0.67%, 0.81%, and 0.91, respectively. In a second validation test, only Model II of AL-500 and CS-200 was evaluated separately based on data from 24 feedlot steers. The overall mean bias, absolute difference, and standard error of prediction of AL-500 Model II were 0.71, 0.92, and 0.98%. For CS-200 Model II, the corresponding values were 0.59, 0.97, and 1.03%. Both AL-500 and CS-200 equipment can be used to accurately predict PIMF in live cattle. Further improvement in the accuracy of prediction equations could be achieved through increasing the development data set and the variation in PIMF of cattle used. PMID- 11204691 TI - Carcass traits, cut yields, and compositional end points in high-lean-yielding pork carcasses: effects of 10th rib backfat and loin eye area. AB - Pork carcasses (n = 133) were used to investigate the influence of carcass fatness and muscling on composition and yields of pork primal and subprimal cuts fabricated to varying levels of s.c. fat. Carcasses were selected from commercial packing plants in the southeastern United States, using a 3 x 3 factorial arrangement with three levels of 10th rib backfat depth (< 2.03, 2.03 to 2.54, and > 2.54 cm) and three levels of loin eye area (LEA; < 35.5, 35.5 to 41.9, and > 41.9 cm2). Sides from the selected carcasses were shipped to the University of Georgia for carcass data collection by trained USDA-AMS and University of Georgia personnel and fabrication. Sides were fabricated to four lean cuts (picnic shoulder, Boston butt, loin, and ham) and the skinned belly. The four lean cuts were further fabricated into boneless cuts with s.c. fat trim levels of 0.64, 0.32, and 0 cm. The percentages of four lean cuts, boneless cuts (four lean cuts plus skinned, trimmed belly) at 0.64, 0.32, and 0 cm s.c. fat, fat-free lean, and total fat were calculated. Data were analyzed using a least squares fixed effects model, with the main effects of 10th rib backfat and LEA and their interaction. Fatness and muscling traits increased (P < 0.05) as 10th rib backfat and LEA category increased, respectively. However, fat depth measures were not affected greatly by LEA category, nor were muscling measures greatly affected by backfat category. The percentage yield of cuts decreased (P < 0.05) as backfat category increased. Cut yields from the picnic shoulder, Boston butt, and belly were not affected (P > 0.05) by LEA category, whereas the yield of boneless loin and ham increased (P < 0.05) as LEA category increased. Compositionally, the percentage of four lean cuts, boneless cuts at varying trim levels, and fat-free lean decreased incrementally (P < 0.05) as backfat depth increased, whereas parentage total fat and USDA grade increased (P < 0.05) as backfat depth increased. As LEA increased, percentage boneless cuts trimmed to 0.32 and 0 cm s.c. fat and fat free lean increased and total fat decreased; however, the difference was only significant in the smallest LEA category. Collectively, these data show that decreased carcass fatness plays a greater role in increasing primal and subprimal cut yields and carcass composition than muscling even in lean, heavily muscled carcasses. PMID- 11204692 TI - Intermuscular variation in tenderness: association with the ubiquitous and muscle specific calpains. AB - The biochemistry of intermuscular variation in tenderness is not fully understood. To investigate the role of the calpains in this process we performed two experiments using bovine and ovine species. In the bovine experiment, two distinct muscles, longissimus thoracis et lumborum (LT) and psoas major (PM), were used. In the ovine experiment, four muscles, LT, PM, semimembranosus (SM), and semitendinosus (ST), were used. Muscles were sampled at death for the determination of the steady-state mRNA level of calpains and calpastatin and the activities of calpain 1, 2, and calpastatin. Muscles were also sampled to determine the temporal changes in pH, tenderness, and the activity of the ubiquitous calpain system during postmortem aging. The results of the relative rate of tenderization in both species was found to be related to muscle type; LT had the highest value in both species. Within species, the mRNA steady-state levels of calpain 1 and calpastatin were similar in various bovine and ovine muscles. Bovine calpain 2 mRNA level was significantly lower in the LT than in the PM. Ovine calpain 2 mRNA level was lower, but not significantly different, in the LT compared to the other muscles. The mRNA level of bovine calpain 3 was significantly higher in the LT muscle than in the PM. In the ovine, the mRNA level of calpain 3 was highest in the LT, followed by SM, PM, and ST. Results on the activity of the ubiquitous calpain system in various muscles at death were dependent on muscle type and species. Temporal changes in the activity of calpains and calpastatin during the first 24 h of postmortem aging were similar in the muscles studied: calpain 1 and calpastatin declined significantly and calpain 2 remained relatively unchanged. The temporal changes in muscle pH in both experiments indicated that the extent and rate of pH decline during aging was related to muscle type. Correlation analysis between the relative rate of tenderization and mRNA expression of calpains revealed a strong relationship with calpain 3 in both species. PMID- 11204693 TI - Manipulation of cattle growth to target carcass quality. AB - Two trials were conducted to determine the effects of breed type, backgrounding program, and backfat end point (USBFEP) as determined by ultrasound on the performance and carcass characteristics of feedlot steers. Trial 1 utilized 144 large-framed Charolais- (304.6 +/- 16.3 kg) and 144 medium-framed Hereford-cross steers (294.8 +/- 20.9 kg). Trial 2 utilized 88 medium-framed Angus (289.5 +/- 15.0 kg), 88 large-framed Charolais- (299.8 +/- 17.7 kg), and 88 medium-framed Hereford-cross (291.1 +/- 20.9 kg) steers. Within breed type, short- (70 d) or long-term (126 d) backgrounding programs (Trial 1) and 6- or 12-mm USBFEP (Trials 1 and 2) were assigned. In both trials, carcass size was greater (P < 0.05) for the large-framed Charolais-cross steers, longer backgrounding, and fatter USBFEP treatments. Lean meat yield was greater (P < 0.05) for Charolais- than Hereford cross steers (Trial 1) and for the leaner USBFEP (Trials 1 and 2). Marbling was greater (P < 0.05) for Angus- (Trial 2) and Charolais- (Trials 1 and 2) than Hereford-cross steers (Trials 1 and 2) and for the fatter end point (Trials 1 and 2). It was concluded that breed type, backgrounding program, and USBFEP were effective in altering growth and could be used to target carcass traits of interest for value-based marketing programs. PMID- 11204694 TI - Effect of supplemental vitamins and trace minerals on performance and carcass quality in finishing pigs. AB - Two trials with finishing pigs (PIC line 355 x Camborough 22) were conducted to evaluate the effects of vitamin and trace mineral (VTM) supplement deletions on performance, carcass quality, and tissue nutrient levels. Trial 1, a 3 x 2 factorial arrangement of treatments involving three VTM supplement regimens and two stress regimens, was conducted for 12 wk with 252 pigs (mixed sex). Average initial weight of pigs was 54 kg. The VTM regimens consisted of control (adequate level of VTM throughout trial), VTM deleted for the final 6 wk, and VTM deleted for entire 12 wk of the trial. The stress regimens consisted of leaving half the treatments in their original location or moving the other half of the treatments to a new pen location every 3 wk. There were three replications (pens) per treatment with 14 pigs per pen (0.80 m2). Diets were medicated with bacitracin methylene disalicylate. Overall, there were no treatment differences (P > 0.05) for ADG, ADFI, gain:feed ratio, longissimus muscle area, or last-rib backfat. However, there was a greater than 75% decrease (P < 0.001) in vitamin E content of longissimus muscle from deleting VTM for 6 or 12 wk. Trial 2, a 3 x 2 factorial arrangement of treatments involving three VTM regimens and two genders, was conducted for 12 wk with 306 pigs. Average initial weight of pigs was 58 kg. The VTM regimens were identical to those used in Trial 1. Each treatment consisted of three gender replications of 17 pigs per pen (0.66 m2), and all diets were unmedicated. Overall, pigs fed diets without VTM for 12 wk had lower (P < 0.06) ADG than those fed the control diets. Vitamin E content of the ham muscle was reduced by greater than 50% (P < 0.001) when pigs were fed diets without VTM for 6 or 12 wk compared with those fed the control diet. Concentrations of copper in ham muscle were reduced (P < 0.05) in pigs fed diets without VTM. These data suggest that deleting VTM during the finishing stage markedly lowers the vitamin E content of pork muscle. PMID- 11204695 TI - Effects of dietary fermentable carbohydrates on energy metabolism in group-housed sows. AB - The effect of dietary nonstarch polysaccharide (NSP) content on the metabolic rate in group-housed sows was studied. Twelve groups of six nonpregnant sows were each fed one of four experimental diets similar in composition except for the starch and NSP content. Exchanging sugar beet pulp silage (SBPS) for tapioca created the difference in starch and NSP ratio in the diet. On a DM basis, diets contained 0, 10, 20, or 30% SBPS. Sows were group-housed and fed at 1.30 times the assumed maintenance energy requirements. Nitrogen and energy balances were measured per group during a 7-d experimental period, which was preceded by a 33-d adaptation period. Both digestibility and metabolizability of energy decreased with increasing dietary SBPS content (P < 0.05). Heat production and energy retention were unaffected by the exchange of starch for NSP (P > 0.1). Based on energy retention data and apparent fecal digestibilities of crude protein, crude fat, starch, and NSP, the estimated net energy value of fermented NSP was 13.4 kJ/g. The present study shows that group-housed sows are capable of using energy from fermented NSP (i.e., NSP from SBPS) as efficiently as energy from digested starch (i.e., starch from tapioca). PMID- 11204697 TI - Gross anatomical and histomorphometric characteristics of the oviduct and uterus during the pubertal transition in sheep. AB - Gross anatomical and histometric characteristics of oviducts and uteri were evaluated during the pubertal transition in ewe lambs. Lambs were hysterectomized prepubertally (PP; n = 10) or 26 +/- 2 h after onset of first (FE; n = 13) or third estrus (TE; n = 12), or estrus in mature pluriparous ewes (ME; n = 4). Gross characteristics included diameters, lengths, and weights of oviducts; diameters of uterine cornua; and weights of uteri. Histometric characteristics of ampullae, isthmi, and uterine cornua included epithelial cell volume, total luminal surface area, and total number of cells per ampulla or isthmus and area of the muscularis. Side of the reproductive tract did not affect (P > 0.10) any gross or histometric characteristic. Gross uterine characteristics increased (P < 0.05) dramatically between PP ewes and FE ewes, and then increased (P < 0.05) to a lesser degree between FE and TE ewes, and again (P < 0.05) between TE and ME ewes. Histological characteristics of uteri followed a similar developmental pattern: large changes (P < 0.05) between PP and FE ewes, slight increases between FE and TE ewes, and no change (P > 0.10) between TE and ME ewes. Oviductal weight and length showed little change (P > 0.10) at puberty or by third estrus, but they were greater (P < 0.05) in ME ewes than in the other groups. The diameters of ampullae increased (P < 0.05) at puberty, showed no change between FE and TE ewes, and were greatest (P < 0.05) in mature ewes. These changes seemed to be due to increases (P < 0.05) in mucosal cell height and muscularis area at puberty, and to muscularis area and submucosal thickness between TE and ME ewes. The surface area of the ampullae increased (P < 0.05) at puberty or by third estrus in a linear manner between PP, FE, TE, and ME ewes. The diameters of isthmi did not change (P > 0.10) at puberty but increased (P < 0.05) between FE and TE, and were greatest (P < 0.05) in ME ewes. The histological characteristics of isthmi followed the pattern observed in the ampullae. However, the surface area of the isthmi showed no change (P > 0.10) at puberty or by third estrus and was largest (P < 0.05) in ME ewes. Results of this study indicate that gross morphological characteristics of uteri and oviducts increase at puberty with either slight increases or changes after two estrous cycles. This relationship is also reflected by histological characteristics of these organs during the pubertal transition of sheep. PMID- 11204696 TI - Uptake and excretion of organochlorine compounds in neonatal calves. AB - Intestinal absorption mechanisms of young calves change rapidly during the first 24 h postpartum and subsequently effect the absorption efficiencies of a wide range of compounds. This study was conducted to determine absorption efficiencies of (p,p'-dichlorodiphenyl)dichloroethylene (DDE), 2,2',4,4',5,5' hexachlorobiphenyl (PCB-153), and 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin (OCDD) when administered in colostrum to neonatal calves. Four male Holstein calves were given a single oral dose containing 100 mg each of DDE, PCB-153, and OCDD either 1 h (n = 2) or 65 h (n = 2) postpartum to determine whether time of exposure influenced the rate or extent of absorption. Another male calf received 100 mg each of DDE and OCDD 1 h postpartum. One gram of chromic oxide (Cr2O3) was administered as a digestion marker to dosed calves. Two male calves, receiving only colostrum, served as controls. Serum IgG concentrations indicated that the 1 h calves absorbed 20 to 37% of the ingested IgG and 65-h calves < 2%; therefore, the gut absorption mechanisms had changed by 65 h. Plasma DDE, PCB-153, and OCDD profiles did not differ based on time of exposure, suggesting that their mechanism of absorption was not influenced by the changing gut. Trapezoidal area under the curve to the last time point values indicated that, during the trial, relative plasma organochlorine concentrations amounted to PCB-153 > DDE > OCDD. Tissue concentrations were similar across treatment groups, with DDE and PCB-153 residues concentrating in adipose tissue and OCDD in the liver. Absorption efficiencies, calculated from fecal recoveries, were >97%, >74%, and >72% for DDE, PCB-153, and OCDD, respectively. These doses of DDE, PCB-153, and OCDD (2.5 +/- 0.1 mg/kg) did not produce signs of toxicosis based on detailed clinical observations, serum clinical chemistry, and gross and histological observations at necropsy. The results of this study indicate that DDE, PCB-153, and OCDD were absorbed and distributed similarly in calves exposed 1 or 65 h postpartum and did not induce toxicosis when administered in combination at these concentrations. PMID- 11204698 TI - Endocrine relationships of Meishan and White composite females after weaning and during the luteal phase of the estrous cycle. AB - Endocrine differences between European crossbred and Chinese Meishan females have been somewhat modest. Indwelling jugular cannulas were placed in Meishan (n = 7) and White composite (n = 6) multiparous sows before weaning, and blood was sampled from 4 h before to 240 h after removal of litters. Temporal changes in FSH, triiodothyronine (T3), and tetraiodothyronine (T4) after weaning differed between Meishan and White composite sows. Plasma cortisol concentrations were higher in Meishan sows than in White composite sows (P < 0.01), but there were no temporal differences between breeds after weaning. Other hormones monitored (prolactin, GH, IGF-I, and inhibin) were not different between breeds. In the second experiment, Meishan gilts (n = 7) and sows (n = 7) and White composite sows (n = 9) were cannulated during the luteal phase of the estrous cycle and sampled after treatments consisting of GnRH (15 and 150 ng/kg BW), ovariectomy, estradiol cypionate challenge after ovariectomy (10 microg/kg BW), and GnRH antagonist. In response to GnRH challenge, White composite sows had elevated (P < 0.05) concentrations of gonadotropins compared with Meishan. Cortisol concentrations were elevated in Meishan as compared with White composite females (P < 0.01) but unaffected by GnRH treatment. After ovariectomy, LH concentrations increased 3 h sooner in White composite than in Meishan females. After GnRH antagonist, declines in gonadotropins were comparable in both breeds, but LH increased in Meishan females by 20 h but not until after 54 h in White composite females. White composite females demonstrated only a short decline in FSH in response to the GnRH antagonist, but Meishan females had a prolonged decline in FSH concentrations. Consistently elevated cortisol concentrations in Meishan females may positively impact ovarian function; thus, the assumption that high plasma cortisol concentration as an index of stress that impairs reproductive function should be reevaluated in swine. There were few endocrine differences that would relate to or explain increased ovulation rates found in the Meishan breed; thus, other mechanisms must exist to explain the increase in ovarian function in the Meishan breed. PMID- 11204699 TI - Intravenous infusion of iron and tetrahydrofolate does not influence intrauterine uteroferrin and secreted folate-binding protein content in swine. AB - The effect of exogenous iron and folate on reproductive performance in swine is equivocal. However, the effect of exogenous iron and folate on secretion of their respective uterine transport proteins has never been reported. Twenty gilts were infused (n = 5 per treatment) with either 1) saline, 2) alpha-tocopherol, 3) alpha-tocopherol plus iron citrate, or 4) alpha-tocopherol plus tetrahydrofolate on d 11 to 14 of pregnancy. Intravenous infusion of iron citrate and tetrahydrofolate increased (P < 0.05) plasma iron and folate, respectively, for 6 to 8 h after treatment. Treatments had no effect on uterine content of uteroferrin or secreted folate-binding protein in uterine flushings obtained on d 15 of pregnancy. These data suggest that uterine secretion of uteroferrin and secreted folate-binding protein are not influenced by plasma levels of iron and folate, respectively, and may provide an explanation for the equivocal effect of iron and folate treatment on reproductive performance in gilts. PMID- 11204700 TI - Effects of grain sorghum planting density and processing method on nutrient digestibility and retention by ruminants. AB - Grain sorghum grown in 38-cm rows (high density [HD]) or 76-cm rows (normal density [ND]) was treated as follows: steam-flaked (SF), high-moisture-harvested followed by rolling and ensiling (HM), or dry-rolled (DR). Resulting grains were evaluated using lambs in two 5 x 5 Latin square digestion trials. Treatment diets contained either SF-HD, SF-ND, HM-HD, HM-ND, or DR-ND grain sorghum in two trials; a 90 or a 60% concentrate diet was fed in each trial. High-density planting increased (P < 0.10) the apparent absorption of P relative to ND planting for both 60 and 90% concentrate diets. Steam flaking decreased (P < 0.10) the apparent absorption of P in the 90% concentrate diet and decreased (P < 0.10) the apparent absorption of N in both the 90 and 60% concentrate diets. Despite differences in N digestibility, steam flaking and HM ensiling resulted in similar (P > 0.10) N retention as a percentage of N intake in both trials. However, changes in the distribution of N between feces and urine among processing methods could affect N content of manure and alter nutrient management strategies. These results indicate that both planting density and grain processing can alter the apparent absorption of grain sorghum P by ruminants. Furthermore, it seems that grain processing can alter the route of N excretion in ruminants without changing total N retention. PMID- 11204701 TI - Effect of excess degradable intake protein on early embryonic development, ovarian steroids, and blood urea nitrogen on days 2, 3, 4, and 5 of the estrous cycle in mature ewes. AB - Two trials were conducted to determine whether feeding excess degradable intake protein (DIP) during a synchronized estrous cycle and the first 5 d after breeding alters early embryonic development, ovarian steroids, or BUN concentrations in ewes. Ewes were group-fed in Trial 1 (T1) and individually fed in Trial 2 (T2) either 100 (control; T1, n = 15; T2, n = 12) or 200% (high protein; T1, n = 16; T2, n = 12) of the NRC protein recommendation for maintenance during a synchronized estrous cycle until surgery in the next cycle. Ampullae (AMP), isthmi (IST), and uterine horns (UT) of high-protein and control ewes were removed on d 2 (T1), 3 (T2), 4 (T1), or 5 (T2) after breeding. In T1, jugular blood samples were taken once daily starting on d 2 of the synchronized cycle, and in T2 on d 2, 9, 15, 16, and 17, and in both trials from estrus (d 0) to the day of surgery. Ampullae, IST, and UT flushings were examined microscopically for the presence of embryos, embryo condition, and embryo cell number. There was no trial x treatment interaction (P > or = 0.10), so data for both trials were pooled. Concentrations of BUN were higher (P < 0.05) in high protein-fed ewes than in control ewes during the synchronized cycle and the first 5 d of the next cycle. Progesterone concentrations of the synchronized cycle did not differ (P > 0.10) between treatments. During the first 5 d of the next cycle, estradiol-17beta concentrations were lower (P = 0.06) in high-protein-fed than in control ewes. Progesterone increased (P < 0.05) to higher concentrations by d 5 in high-protein-fed ewes than in control ewes. More (P < 0.05) embryos were found in AMP of high-protein-fed ewes than in AMP of control ewes on d 4. Fewer (P = 0.05) embryos were found in UT of high-protein-fed ewes than in UT of control ewes on d 4. More embryos were found in UT of high-protein-fed ewes than in UT of control ewes on d 5. Fewer (P = 0.05) embryos were found in IST of high-protein ewes than in the IST of control ewes on d 5. Embryos of high-protein-fed ewes had more (P < 0.05) cells than embryos from control fed ewes on d 5. Feeding ewes excess DIP protein during an estrous cycle and the first 5 d after breeding initially impeded embryo transport; thereafter, embryo transport and development through the oviduct was accelerated. PMID- 11204703 TI - Preference by sheep and goats among hay of eight tall fescue cultivars. AB - Grazing ruminants use both visual cues and taste in selecting their diet. Preference during grazing may not be the same when forage is dried for hay and cut into lengths prior to feeding in confinement. Eight cultivars of tall fescue (Festuca arundinacea Schreb.), previously evaluated for preference while grazed, were harvested three times over a period of 2 yr. The hays were air-dried, baled, and passed through a hydraulic bale processor prior to feeding. Five experiments were conducted. All three harvests were evaluated with sheep and the last two also with goats, using six animals each time. During an adaptation phase, hays were offered alone as meals. In the experimental phase, every possible pair of hays (28 pairs) was presented for a meal. Data were analyzed by multidimensional scaling and by traditional analyses. Preference was significant among cultivars in all experiments. Multidimensional scaling showed that selection was based on two criteria with two dimensions being significant. Sheep preferred KENHY followed by KENTUCKY 31 and STARGRAZER but preferenced against BARCEL. HIMAG, MO 96, and C1 were intermediate and MOZARK was variable. Goats were similar to sheep in preferring KENHY followed by STARGRAZER and selected against MOZARK and BARCEL. KENTUCKY 31, HIMAG, MO-96, and C1 were intermediate. In all five experiments, the general association was positive for available carbohydrate fractions and negative for fiber fractions that contribute to cell wall rigidity. PMID- 11204702 TI - Effects of different patterns of feed restriction and insulin treatment during the luteal phase on reproductive, metabolic, and endocrine parameters in cyclic gilts. AB - The objectives of the present study were 1) to study potential effects of previous nutritional treatment on developmental competence of early fertilized oocytes in vitro; 2) to study responses to insulin treatment during the period of feed restriction in the late luteal phase which has deleterious effects on subsequent fertility; and 3) to establish the metabolic and endocrine status of gilts during treatment and the subsequent periestrous period. Nineteen trios of littermate gilts were subjected to feed restriction during the first (RH) or second (HR) week of the estrous cycle. A second group of HR gilts received injections of long-acting insulin during their period of feed restriction (HR+I). Intensive sampling was performed in a subgroup of 23 animals on d 15 and 16 of the cycle for analyses of endocrine (gonadotropins and steroid hormones) and metabolic (insulin, IGF-I, leptin, total triiodothyronine [T3], and free T3) variables. Gilts were checked for estrus every 6 h, and time of ovulation was monitored by transcutaneous ultrasonography. Surgeries were performed 12 to 20 h after ovulation, and the early-fertilized oocytes recovered were cultured in vitro under standardized conditions. There was no treatment effect on the developmental competence of fertilized oocytes in vitro; however, ovulation rate was increased in HR+I gilts. No effect of treatment was observed on plasma leptin and IGF-I concentrations on d 15 and 16. However, HR+I gilts had higher (P < 0.05) postprandial insulin and lower (P < 0.05) postprandial total and free T3 on d 15. Plasma concentrations of LH, FSH, and progesterone on d 15 and 16 and plasma estradiol concentrations on d 16 were not affected by previous nutritional or insulin treatment. In the periestrous period, plasma concentrations of LH, FSH, and estradiol were higher (P < 0.05) in RH and HR+I, and the rise in plasma progesterone after the LH surge was lower (P < 0.05), than in HR gilts. No effect of treatment was observed on plasma concentrations of metabolic hormones, except on plasma leptin concentrations, which were higher (P < 0.05) at the time of the LH surge in RH gilts. These results suggest that feed restriction during the late luteal phase may have deleterious effects on ovarian function in the periestrous period, which may be counteracted by insulin. PMID- 11204704 TI - Effect of ruminal vs postruminal administration of degradable protein on utilization of low-quality forage by beef steers. AB - An experiment was designed to determine the effects of ruminal and postruminal infusions of ruminally degradable protein (casein) on intake and digestion of low quality hay by beef steers. Twelve ruminally fistulated Angus x Hereford steers (initial BW = 563 kg) were blocked by weight and assigned to one of three treatments: control (C; hay only) or hay plus ruminal (R) or postruminal (P) infusion of 400 g/d of sodium caseinate. The trial consisted of five periods: 1) 10-d adaptation to the hay diet; 2) 7-d measurement of hay intake (without infusions); 3) 10-d adaptation to protein infusion treatments (intake measurements continued); 4) 7-d measurement of hay intake and digestibility (infusions continued); and 5) 3-d ruminal sampling period (infusions continued). Steers were given ad libitum access to tallgrass-prairie hay (3.4% CP, 76.6% NDF) throughout the study. Casein was administered once daily before feeding, either directly into the rumen or via anchored infusion lines into the abomasum. Hay intake was increased by supplementation (P < 0.01). Ruminal infusion elicited a greater (P = 0.04) increase in hay intake than postruminal infusion. Intake tended (P = 0.11) to be lower in period 4 than in period 2 for control steers but was greater in period 4 than in period 2 (P < or = 0.03) for both R and P steers. The increase in intake between periods 2 and 4 was greater for R than for P steers (P = 0.03). Supplementation improved diet OM digestion (P = 0.04) but not NDF digestion (P = 0.18); however, greater relative error for NDF digestion may have limited the ability to elucidate significant treatment effects. There were no differences in either OM digestion (P = 0.42) or NDF digestion (P = 0.35) between R and P steers. Plasma urea N at 0 and 3 h after feeding on the last day of the experiment was lower (P = 0.05) for C than for R and P steers, but no difference (P = 0.48) was evident between R and P steers. Ruminal ammonia N levels also were increased by supplementation (P < 0.01), with a much larger increase for R than for P steers (P < 0.01). Total VFA concentrations were not affected (P = 0.21) by treatment, but R steers exhibited lower proportions of acetate and higher proportions of isobutyrate, valerate, and isovalerate than P steers (P < 0.01). In conclusion, ruminal and postruminal infusion of a degradable protein source improved forage utilization, although the response in forage OM intake and total digestible OM intake was greater for ruminal infusion than for postruminal infusion. PMID- 11204705 TI - Dietary fat supplementation effects on in vitro nutrient disappearance and in vivo nutrient intake and total tract digestibility by horses. AB - Addition of fat to the diet of the equine is a popular method of increasing energy density of the diet while reducing feed intake. Reducing feed intake is of interest to race horse trainers because additional feed is seen as additional weight and, therefore, a hindrance to performance. Limited information is available regarding the interactions of fat with other dietary components, particularly fiber, in the equine digestive system. The effect of dietary fat on in vitro nutrient disappearance in equine cecal fluid was studied in Exp. 1 using a split-plot design within a 2 x 2 Latin square. Two ponies were fed alfalfa (ALF) alone or alfalfa plus 100 g/d corn oil. Five substrates were used to determine in vitro DM disappearance, OM disappearance, NDF disappearance, and total dietary fiber (TDF) disappearance. The substrates included: ALF, tall fescue (TF), red clover (RC), soybean hulls (SBH), and rolled oats (RO). Fat supplementation did not affect in vitro DM, OM, or NDF disappearance. Addition of fat to the diet increased (P < 0.05) the disappearance of NDF in RO. Among substrates, in vitro DM and OM disappearance were highest (P < 0.05) for RO, followed by SBH, ALF, RC, and TF. In vitro NDF and TDF disappearance were highest (P < 0.05) for SBH, followed by RO, ALF, RC, and TF. In Exp. 2, the effects of varying levels of fat on nutrient intake and total tract digestibility were examined using a 4 x 4 Latin square design. Four mature mares were fed a 60% forage-40% concentrate diet containing different concentrations of fat: 0% supplemental fat control (C); 5% supplemental corn oil (5% CO); 10% supplemental corn oil (10% CO); or 15% supplemental corn oil (15% CO). Treatment did not affect intake of the concentrate portion of the diet or CP, gross energy, or NDF intake. Mares consuming the C diet had the highest (P < 0.05) intake of alfalfa cubes, DM, and OM, followed by those on the 10, 5, and 15% CO treatments, respectively. Treatment did not affect nutrient digestibility. Mares consuming the 15% CO diet had the highest (P < 0.05) fat digestibility, whereas those consuming C had the lowest fat digestibility. Fat in the form of CO generally had little effect on in vitro and in vivo nutrient digestibilities in horses. PMID- 11204706 TI - The effect of energy supplementation on nitrogen utilization in lactating dairy cows fed grass silage diets. AB - An experiment was conducted to examine the effect that various isoenergetic diets, containing different quantities of soluble carbohydrate and fiber and different types of starch, have on nitrogen (N) balances. Six lactating dairy cows in early to midlactation consuming grass silage diets with not less than 600 g/kg total DMI as forage were used in the experiment. Four concentrates were prepared that had higher amounts of either fiber, soluble sugars, corn (low degradable starch source), or barley (high degradable starch source). Overall N utilization by the cows was poor, rarely exceeding 0.30 g milk N/g of dietary N intake. Fecal N outputs accounted for more than half of total N excreted in all treatments except for diets supplemented with high degradable starch, in which urinary N excretion was significantly higher compared with the other treatments. Milk yield was unaffected by concentrate type, averaging 19.9 kg/d, but milk protein content decreased from 32.9 for starch-based diets to 30.9 and 30.0 g/kg for the soluble sugar- and fiber-based diets, respectively. The efficiency of N utilization improved in the low degradable starch treatment, which had lower N excretion (65%) and higher protein concentration in milk. Furthermore, feeding cows corn-based concentrates reduced urinary N excretion by almost 30% compared with barley-based concentrates; therefore, feeding corn-based diets is recommended for the reduction of nitrogen pollution in lactating dairy cows. PMID- 11204707 TI - The effect of protein supplementation on nitrogen utilization in lactating dairy cows fed grass silage diets. AB - The study set out to examine the effects of supplementing grass silage with various levels of protein concentration and degradability on dietary nitrogen (N) excretion in lactating dairy cows consuming at least 60% forage. Six Holstein/Friesian cows in early to midlactation were offered six diets comprising two levels of crude protein (210 and 290 g/kg DM) and three levels of protein degradability in the concentrate achieved using different amounts of untreated or formaldehyde-treated soybean meal. Despite a difference of almost 100 g/d in N intake, apparent fecal and milk N outputs were not significantly affected. Protein degradability also had no effect on N outputs in feces and milk. However, there was a major effect of both level and degradability of CP on urinary N output. Moreover, an interaction between level and degradability of CP was detected, such that the rate at which urinary N increases with increasing CP degradability was higher on the high-CP than on the low-CP diet. A low level of protein (150 g/kg DM in the diet) and medium to low rumen-degradable protein supplements provided a significant reduction in N excretion without compromising lactational performance (mean 24.8 kg/d), in terms of both milk yield and composition. This study also demonstrated that a high efficiency of N utilization could be achieved on low-CP diets (supplying less than 400 g N/d), with feces being the main route of N excretion, whereas an exponential excretion of urinary N was observed as N intake exceeded 400 g N/d. PMID- 11204709 TI - Efficient computation of genotype probabilities for loci with many alleles: I. Allelic peeling. AB - Genetic marker data are likely to be obtained from a relatively small proportion of the individuals in many livestock populations. Information from genetic markers can be extrapolated to related individuals without marker data by computing genotype probabilities using an algorithm referred to as peeling. However, genetic markers may have many alleles and the number of computations in traditional peeling algorithms is proportional to the number of alleles raised to the sixth or eighth power, depending on pedigree structure. An alternative algorithm for computing genotype probabilities of marker loci with many alleles in large, nonlooped pedigrees with incomplete marker data is presented. The algorithm is based on recursive computations depending on alleles instead of genotypes, as in traditional peeling algorithms. The number of computations in the allelic peeling algorithm presented here is proportional to the square of the number of alleles, which makes this algorithm more computationally efficient than traditional peeling for loci with many alleles. Memory requirements are roughly proportional to the number of individuals in the pedigree and the number of alleles. The recursive allelic peeling algorithm cannot be applied to pedigrees that include full sibs or loops. However, it is a preliminary step toward a more complex and encompassing iterative approach to be described in a companion paper. PMID- 11204708 TI - Effects of L-carnitine on nitrogen retention and blood metabolites of growing steers and performance of finishing steers. AB - Two experiments were conducted to evaluate L-carnitine supplementation to cattle fed grain-based diets. In Exp. 1, seven Angus-cross steers (216 kg) were used in a 7 x 4 incomplete Latin square experiment to evaluate the effects of supplemental L-carnitine on N balance and blood metabolites. Steers were fed a corn-based diet (17.5% CP) at 2.5% of BW. Treatments were 0, 0.25, 0.5, 1.0, 1.5, 2.0, and 3.0 g/d of supplemental carnitine. The 18-d periods included 13 d for adaptation and 5 d for collection of feces and urine. Blood was collected before feeding and 3 and 6 h after feeding on d 18 of each period. Dry matter intakes tended to be highest when 1.5 g/d of carnitine was supplied, but N retention was not affected by carnitine and averaged 29.3 g/d. Plasma carnitine concentrations and urinary excretion increased with increasing carnitine supply, indicating that at least some of the carnitine escaped ruminal degradation and was absorbed by the steers. Plasma concentrations of NEFA demonstrated a treatment x time interaction; they decreased linearly in response to carnitine before feeding but increased linearly in response to carnitine at 6 h after feeding. Serum insulin and plasma glucagon, IGF-I, cholesterol, triglyceride, and amino acids were not affected by carnitine. Plasma concentrations of glucose, glycerol, urea, and beta hydroxybutyrate all were increased by some of the levels of carnitine supplementation, but results for these measurements did not follow easily described patterns and seemed to be related to differences in DMI. In Exp. 2, 95 crossbred steers (357 kg initial BW) were fed finishing diets (14.5% CP) for 129 d. Diets were based on steam-flaked corn and contained 6% alfalfa and 4% tallow. Feed intakes, gains, and feed efficiencies were not affected by supplementation with 2 g/d L-carnitine. However, steers receiving L-carnitine tended to have fatter carcasses, as indicated by tendencies (P < 0.2) for thicker backfat, higher marbling scores, and higher yield grades. In conclusion, carnitine supplementation did not alter lean deposition in growing steers but it did alter plasma NEFA concentrations of growing steers fed a corn-based diet and also seemed to increase fat deposition in finishing cattle. PMID- 11204711 TI - Evaluation of the 1996 NRC beef model under western Canadian environmental conditions. AB - Two feedlot trials were conducted to evaluate the 1996 NRC beef model under western Canadian conditions. In the first trial, 144 Charolais- (304.6 +/- 16.3 kg) and 144 Hereford- (295.1 +/- 20.8 kg) cross steers were used, whereas the second trial used 88 Angus- (289.7 +/- 15.0 kg), 88 Charolais- (299.8 +/- 17.9 kg), and 88 Hereford- (291.1 +/- 20.9 kg) cross steers. Diets were based on barley silage, rolled barley grain, canola meal, and cereal straw and were analyzed according to the 1996 NRC methodologies. Animal performance and environmental data were collected for 24 pens of steers per trial for the backgrounding and finishing periods. Levels 1 and 2 of the 1996 NRC model were used to generate predictions of DMI and ADG for each pen. Results showed that actual finishing DMI was accurately predicted for Trial 1 and for the combined trials but not for Trial 2. Predicted ADG was lower (P < 0.05) than actual ADG for all feeding periods except Level 1 of the Trial 1 finishing period. All ADG residuals were significant (P < 0.05), indicating inaccurate prediction of ADG in all feeding periods. The 1996 NRC model consistently predicted that protein was not limiting gain. Further investigations and model refinement regarding animal energy requirements under cold weather conditions and effects of limit feeding are required to increase the accuracy of the 1996 NRC model in predicting animal performance. PMID- 11204710 TI - Zinc and copper status in ewes supplemented with sulfate- and amino acid complexed forms of zinc and copper. AB - Thirty 6-yr-old Targhee ewes were randomly allotted to one of five supplemental treatments to evaluate supplementation effects on liver and fecal Zn and Cu concentrations and serum alkaline phosphatase activity: 1) control, 2) Zn complex, 3) Zn and Cu (ZnCu) complex, 4) Zn sulfate, and 5) ZnCu sulfates. Supplements were administered daily in gelatin capsules for 56 d. Liver biopsies and serum samples were collected every 14 d starting on d 0. Supplemental Zn and Cu levels were formulated to provide 90 mg/kg Zn and 10 mg/kg Cu, respectively, on a daily dry matter intake basis. Form (complex vs sulfate) x type (Zn vs ZnCu) interactions were not detected (P > 0.35). Therefore, contrast statements were used to make the following treatment comparisons: 1) control vs supplement, 2) Zn vs ZnCu, and 3) complex vs sulfate. Ewe BW at the end of the study (P = 0.09) and ewe BW change from beginning to end of the study (P = 0.07) were greater for supplemented than control ewes. Body weight and BW change did not differ between sulfate and complex (P > 0.39) or Zn- and ZnCu- (P > 0.40) supplemented ewes. Liver Cu concentrations did not differ (P = 0.41) between control and supplemented ewes. Liver Cu concentrations were higher (P < 0.10) for ewes supplemented with ZnCu than Zn and complex than sulfate forms of supplement. Liver Zn concentration tended (P = 0.13) to be higher in ZnCu than Zn supplemented ewes. Liver and fecal Zn concentration were higher (P < 0.06) in ewes fed complex than sulfate supplements. However, serum alkaline phosphatase activity tended (P = 0.12) to be greater in ewes fed sulfate than complex supplements. Supplementing mature ewes with complexed minerals resulted in higher concentrations of Zn and Cu in the liver. In addition, supplemental Cu tended to increase concentrations of Zn in the livers of ewes; however, high levels of supplemental Zn did not negatively impact liver Cu concentrations. PMID- 11204712 TI - Efficient computation of genotype probabilities for loci with many alleles: II. Iterative method for large, complex pedigrees. AB - An algorithm for computing genotype probabilities for marker loci with many alleles in large, complex pedigrees with missing marker data is presented. The algorithm can also be used to calculate grandparental origin probabilities, which summarize the segregation pattern and are useful for mapping quantitative trait loci. The algorithm is iterative and is based on peeling on alleles instead of the traditional peeling on genotypes. This makes the algorithm more computationally efficient for loci with many alleles. The algorithm is approximate in pedigrees that contain loops, including loops generated by full sibs. The algorithm has no restrictions on pedigree structure or missing marker phenotypes, although together those factors affect the degree of approximation. In livestock pedigrees with dense marker data, the degree of approximation may be minimal. The algorithm can be used with an incomplete penetrance model for marker loci. Thus, it takes into account the possibility of marker scoring errors and helps to identify them. The algorithm provides a computationally feasible method to analyze genetic marker data in large, complex livestock pedigrees. PMID- 11204713 TI - Genetic (co)variances for calving difficulty score in composite and parental populations of beef cattle: I. Calving difficulty score, birth weight, weaning weight, and postweaning gain. AB - Heritability of 2-yr-old heifer calving difficulty score was estimated in nine purebred and three composite populations with a total of 5,986 calving difficulty scores from 520 sires and 388 maternal grandsires. Estimates were 0.43 for direct (calf) genetic effects and 0.23 for maternal (heifer) genetic effects. The correlation between direct and maternal effects was -0.26. Direct effects were strongly positively correlated with birth weight and moderately correlated with 200-d weight and postweaning gain. Smaller negative correlations of maternal calving difficulty with direct effects of birth weight, weaning weight, and postweaning gain were estimated. Calving difficulty was scored from 1 to 7. Predicted heritabilities using seven optimal scores were similar to those using four scores. The predicted heritability using only two categories was reduced 23%. Phenotypic and direct genetic variance increased with increasing average population calving difficulty score. The estimated direct and maternal heritabilities for 2-yr-old calving difficulty score were larger than many literature estimates. These estimates suggested substantial variance for direct and maternal genetic effects. The direct effects of 2-yr-old calving difficulty score seemed to be much more closely tied to birth weight than were maternal effects. PMID- 11204714 TI - Effect of oxygen inhalation at birth on the reduction of early postnatal mortality in pigs. AB - Asphyxia during delivery is considered a main cause of stillbirth in pigs, but piglets suffering from intermittent asphyxia during delivery are also less viable at birth and less prone to adapt to extrauterine life. In an effort to improve pig viability, one attractive solution would be to increase oxygen supply through oxygen inhalation by the newborn pig. The objective of this study was to test effects of oxygen inhalation immediately after birth on various physiological parameters and piglet survival. The experiment was performed on 252 Pietrain x Large White piglets, half of them reoxygenated immediately after birth. They were maintained during 20 min in a chamber where oxygen concentration was monitored at 40% and were then put back with the sow and the control pigs. Oxygen inhalation affected piglet metabolism. Through stimulation of oxidative metabolism (reduction of circulating levels of lactate) and lowering of the level of postnatal hypothermia (particularly for the lightest pigs), oxygen inhalation increased piglet viability and reduced mortality during the 1st d of life by 75% (2 vs 8%). No additional effects were observed during the following days and overall mortality between birth and weaning at 21 d was reduced from 12 to 8%. PMID- 11204715 TI - Genetic (co)variances for calving difficulty score in composite and parental populations of beef cattle: II. Reproductive, skeletal, and carcass traits. AB - There is limited genetic information relating calving difficulty and body weights to other productive and reproductive traits. Such information is useful for specifying selection criteria and for predicting economic consequences of selection. Genetic, maternal, and environmental covariances of six productive and reproductive measurements with calving difficulty, birth weight, 200-d weight, and 168-d postweaning gain were estimated in 12 experimental populations of cattle. Calf (direct) genetic effects resulting in longer gestation length were associated with increased calving difficulty and birth weight. Maternal genetic effects of increased gestation length and heavier birth weight were significantly associated. Lighter birth weight and reduced calving difficulty were associated with earlier heifer age at puberty. Increases in direct genetic effects of calving difficulty, 200-d weight, and postweaning gain were associated with a small increase in direct effect of scrotal circumference. Increased direct genetic effects of scrotal circumference were correlated with maternal effects decreasing calving difficulty and increasing 200-d weight. Direct effects of the skeletal measurements, yearling hip height, and heifer pelvic area were positively correlated with direct effects of calving difficulty, birth weight, 200-d weight, and postweaning gain, positively correlated with maternal effects for birth weight and 200-d weight, and negatively correlated with maternal calving difficulty. Percentage of retail product was positively associated with calving difficulty and negatively associated with 168-d gain. Predicted genetic change in calving difficulty resulting from one standard deviation of selection for either calving difficulty score or birth weight was much larger than for any other traits. Selection for 200-d weight, 168-d postweaning gain, hip height, pelvic area, or scrotal circumference was predicted to have opposite effects on direct and maternal calving difficulty. Estimated genetic correlations indicate some small to moderate relationships between calving difficulty and the measured productive and reproductive traits. However, selection for reduced calving difficulty should be based on calving difficulty score and(or) birth weight because of their superiority in predicted genetic change. PMID- 11204716 TI - Candidate gene analysis for loci affecting litter size and ovulation rate in swine. AB - A candidate gene approach was used to determine whether specific loci explain responses in ovulation rate (OR) and number of fully formed (FF), live (NBA), stillborn, and mummified pigs at birth observed in two lines selected for ovulation rate and litter size compared with a randomly selected control line. Line IOL was selected for an index of OR and embryonic survival for eight generations, followed by eight generations of two-stage selection for OR and litter size. Line C was selected at random for 16 generations. Line COL, derived from line C at Generation 8, underwent eight generations of two-stage selection. Lines IOL and C differed in mean EBV by 6.1 ova and 4.7 FF, whereas lines COL and C differed by 2.2 ova and 2.9 FF. Pigs of Generation 7 of two-stage selection lines were genotyped for the retinol binding protein 4 (RBP4, n = 190) and epidermal growth factor (EGF, n = 189) loci, whereas pigs of Generations 7 and 8 were genotyped for the estrogen receptor (ESR, n = 523), prolactin receptor (PRLR, n = 524), follicle-stimulating hormone beta (FSHbeta, n = 520), and prostaglandin-endoperoxide synthase 2 (PTGS2, n = 523) loci. Based on chi-square analysis for homogeneity of genotypic frequencies, distributions for PRLR, FSHbeta, and PTGS2 were different among lines (P < 0.005). Differences in gene frequencies between IOL vs C and COL vs C were 0.33 +/- 0.25 and 0.16 +/- 0.26 for PRLR, 0.35 +/- 0.20 and 0.15 +/- 0.24 for FSHbeta, and 0.16 +/- 0.16 and 0.08 +/- 0.18 for PTGS2. Although these differences are consistent with a model of selection acting on these loci, estimates of additive and dominance effects at these loci did not differ from zero (P > 0.05), and several of them had signs inconsistent with the changes in allele frequencies. We were not able to find significant associations between the polymorphic markers and phenotypes studied; however, we cannot rule out that other genetic variation within these candidate genes has an effect on the traits studied. PMID- 11204717 TI - Putative quantitative trait locus affecting birth weight on bovine chromosome 2. AB - A genome scan for chromosomal regions influencing birth weight was performed using 151 progeny of a single Hereford x composite bull and 170 microsatellite markers spanning 2.497 morgans on 29 bovine autosomes. A QTL was identified at the telomeric end of bovine chromosome 2 (maximum effect at 114 cM) accounting for approximately 2.8 kg of birth weight or 0.64 residual standard deviations (after adjustment for sex of calf, age of dam, and breed of dam). No significant effect on growth from birth to weaning was detected in this region. The presence of this QTL within a resource herd composed of breeds common to the Northern Great Plains provides an opportunity to initiate marker-assisted selection to reduce birth weight with minimal effect on postnatal growth. Thus, potentially the amount and degree of dystocia can be reduced and the economic loss associated with calving difficulty lessened without compromise of subsequent growth performance. In addition, this finding indicates that significant genetic variation for birth weight (and presumably other production-related traits) exists within herds composed of commercially adapted Bos taurus germplasm. PMID- 11204718 TI - Belly-nosing in early-weaned piglets is not influenced by diet quality or the presence of milk in the diet. AB - Early weaning of piglets can lead to an increase in belly-nosing and other oral nasal behavior (nosing, chewing, or sucking other piglets), but the causative factors involved in these behavior patterns are largely unknown. Because these behavior patterns resemble massaging the udder and sucking, they may be associated with feeding. The objectives of this study were to determine any effect of diet quality or the presence of milk in the diet on belly-nosing behavior of piglets weaned at 14 to 18 d. During the first 2 wk after weaning, piglets were fed diets differing in quality and inclusion of milk products. Six replicates of eight piglets per replicate, blocked by initial body weight, (n = 192) were offered one of four dietary treatments: HQM: high quality, high in milk products; HQ: high quality, no milk products; PQ: poor quality, no milk products; HQ+MR: high quality, no milk products (as HQ) sprayed with milk replacer five times daily. Thereafter, the piglets were fed a standard nursery diet. Feed intake was measured daily for wk 1 and again at the end of wk 2. Behavior was recorded every 5 min during two 4-h periods on d 2 to 7, 10, 14, 17 and 21 after weaning. Dietary treatment influenced ADFI and ADG during wk 1. Average daily feed intake (P < 0.05) and ADG (P < 0.05) of piglets on PQ were less than those of piglets on the other treatments. During wk 2, ADFI (P > 0.10) and ADG (P > 0.10) were the same across all treatments. Overall, ADFI was not influenced by the inclusion of milk products in the diet or the addition of milk replacer (P > 0.10); however, ADG was. Piglets on HQM had higher ADG than those on HQ during wk 2 (P < 0.05) and 3 after weaning (P < 0.05). However, milk replacer did not influence ADG (P > 0.10). Although the dietary treatments did affect ADFI and ADG, there were no effects on any behavior pattern recorded, including time spent at the feeder (P > 0.10). Lower weight-for-age piglets performed more oral-nasal behavior, in total, than higher weight-for-age piglets (P < 0.03). Neither feeding a poor-quality diet nor the presence of milk in the diet had an effect on belly-nosing or other oral-nasal behavior patterns during the first 3 wk after weaning. Belly-nosing does not seem to be associated with feeding. PMID- 11204719 TI - Influence of a high ambient temperature on lipid metabolism in the growing pig. AB - Because pigs are fatter when they are heat-stressed, it was hypothesized that lipid metabolism is enhanced in heat-stressed pigs. To test this hypothesis, an experiment was conducted to determine the influence of a high ambient temperature on the level of plasma lipids, thyroid hormones, lipoprotein lipase activity, and on the composition of very low density lipoproteins (VLDL) and chylomicrons in the growing pig. Twelve Large White x Landrace castrated male pigs with an initial weight of 20 +/- 0.6 kg were allotted to one of the following treatments: 1) ambient temperature of 31 degrees C, with ad libitum access to feed or 2) ambient temperature of 20 degrees C and fed the amount consumed by those kept at 31 degrees C until 35 kg BW. Ambient temperature did not affect piglet performance. Compared to that in pigs kept at 20 degrees C, in pigs kept at 31 degrees C the lipid content of backfat was 26% higher and the proportion of flare fat was increased by more than twofold (P < 0.001). Lipoprotein lipase activity was increased more than twofold in backfat and nearly twofold in leaf fat at 31 vs 20 degrees C (P < 0.001). In warmth-exposed (31 degrees C), feed-restricted pigs, the plasma level of triiodothyronine was 30% lower than at 20 degrees C (P < 0.001), whereas VLDL-lipid concentration was more than fourfold higher, and plasma concentrations of NEFA and triglycerides were 2.6- and 3.6-fold higher, respectively (P < 0.001). In conclusion, the chronic exposure of growing pigs to a high ambient temperature enhances lipid metabolism in both the liver (VLDL production) and the adipose tissue (lipoprotein lipase activity). Consequently, plasma triglyceride uptake and storage are facilitated in the adipose tissue, which results in greater fatness. PMID- 11204720 TI - Effects of repeated cross-fosterings on preweaning behavior and growth performance of piglets and on maternal behavior of sows. AB - Extensive cross-fostering is widely used in early-weaning units in order to standardize and improve body weight at weaning. However, young suckling piglets develop teat fidelity and repeated cross-fosterings could go against this behavior. This experiment was therefore conducted to compare the behavior and growth of 13 control and 14 fostered litters. Once every 3 d (from d 1 to 16 of lactation), all piglets were weighed and three piglets were switched between two fostered litters. Their unfostered littermates were called residents. Behavior was recorded for 2 h after weighing and(or) adoption and during one nursing period 24 h later. Fights were more frequent (P < 0.05) in treated than in control litters during and between nursings at all ages of adoption except d 1. Most fights occurred between resident and fostered piglets (P < 0.001), except at d 1. Fights during nursing were still more frequent in treated than in control litters 24 h after adoption (P < 0.02), except at d 1 and 16. More piglets had skin lacerations in treated than in control litters except at d 1 (P < 0.05), and scratches were more frequent in fostered than in resident piglets at d 1 (P = 0.07), 7, 13, and 16 (P < 0.01). At all ages except d 1, failed nursings and snaps at piglets were more frequent in fostered than in control litters (P < 0.05), most snaps being directed at adopted piglets (P < 0.001). In fostered litters, sows spent 15 to 30% less time lying on their sides at d 4, 7, 13, and 16 (P < 0.05). Finally, adopted piglets were 13% lighter than controls at weaning (P < 0.001), whereas residents were heavier than adopted piglets (P < 0.05) but lighter than controls (P = 0.1). These data demonstrate that cross-fostering done repeatedly during lactation is stressful for piglets and sows and does not improve body weight at weaning. PMID- 11204722 TI - [Time rediscovered]. PMID- 11204721 TI - Coordinate expression of matrix-degrading proteinases and their activators and inhibitors in bovine skeletal muscle. AB - Matrix metalloproteinases (MMP) responsible for degradation of connective tissue are found in most tissues. The MMP are regulated at the levels of transcription, zymogen activation by plasmin or membrane-type- (MT) MMP, and control of enzyme activity by tissue inhibitors of metalloproteinases (TIMP). Whole bovine skeletal muscle showed multiple MMP activities on gelatin zymography and also expressed mRNA encoding MMP-1, -2, -9, -14, and -16, tissue inhibitors of metalloproteinase (TIMP)-1, -2, and -3 and plasminogen activator and its receptor. Purified intramuscular fibroblasts and myogenic cell culture derived from satellite cells expressed most or all of these elements. Statistical analysis (n = 35) revealed a strong positive correlation among the mRNA levels of several elements of the MMP system, including MMP-2, MMP-14, TIMP-1, -2, and -3 (r = 0.614 to 0.930, P < 0.0001). Our results provide an extensive profile of an extracellular proteolytic cascade involving MMP in skeletal muscle and suggest that 1) the activation cascades of muscle MMP may be initiated by both plasmin and membrane-type MMP; 2) a group of genes involved in the same "arm" of zymogen activation are coexpressed in this tissue; and 3) skeletal muscle cells, in addition to the intramuscular fibroblasts, express an extensive complement of MMP and related proteins. PMID- 11204723 TI - [Sociocultural dimension of epilepsy (kirikirimasien) in a Bambara rural area (Mali)]. AB - The anthropological study of kirikirimasien (epilepsy) in Mali constitutes an integral part of a research programme devoted to the epidemiology of epilepsy and onchocerciasis in Mali. This programme is run jointly by scientists of the Ecole Nationale de Medecine et de Pharmacie (National School of Medicine and Pharmacy) of Bamako, Mali, and the Faculte de Medecine (Faculty of Medicine) of Marseilles, France. Preliminary results of the anthropological study are presented, based on the qualitative analysis of 132 interviews, conducted over 6 months. Those interviewed were mainly persons affected by kirikirimasien, but included members of the family circle, traditional healers, and outsiders as well. Participatory interview techniques used the national language bambara. The interviews were unstructured and semi-structured so as to identify themes in the bambara language concerning kirikirimasien. Two dominant trends were identified, concerning the aetiology and nosography of the disease, and the social dimension of kirikirimasien, respectively. In terms of aetiology and nosography, diagnosis, contamination and appelation are--in order of priority--the most important aspects of the disease. Yet the social dimension of kirikirimasien appears largely to surpass its aetiological and nosographic aspects. The social dimension is crucial to the anthropological understanding of kirikirimasien. This was amply illustrated by various references which arose during the interviews. First, how is the notion of contamination represented and which practices are associated with it? Second, invalidity and handicap appear to play an essential role in the way people deal with the disease. The notion of tolerance in the bambara environment is also addressed, mainly through a spatial study of the adherence of the person affected by the disease (family, village and outsiders). The third part of the study deals with the social understanding of kirikirimasien and looks at how those affected are cared for, both within their social setting and in terms of seeking treatment. PMID- 11204724 TI - [Sociocultural aspects of epilepsy in Madagascar. K.A.P. survey carried out in Antananarivo]. AB - A general population survey on knowledge, attitudes and practices (K.A.P.) concerning epilepsy was conducted from 1st July to 31st December 1997 in Antananarivo, a region representative of ecological and cultural patterns of the Malagasy "Highlands". The sample, randomly selected according to the two-step cluster method, recruited 1392 men and women aged 18 years and older who were interviewed with a 16-item questionnaire. Knowledge and practices have significantly evolved since 1983, when a similar study was conducted. More natural explanations are given for the condition and health-care seeking is more common. However, popular attitudes towards the epileptic patient remain contradictory: the majority of those interviewed claimed to be tolerant; work and marriage could be envisaged for the epileptic patient, but not total freedom of movement nor regular school attendance. A more active popularisation of the disease thus appears to be necessary. Since some 60% of people had a radio, broadcasting and church involvement would be the most effective means towards this end. Traditional practicer do not seem to have an overwhelming influence; rather, healthcare seeking behaviour was determined by the availability of service, the efficacy of the intervention and cost. To be representative of Madagascar as a whole, our data should be compared to those of other surveys in more culturally enclosed and disadvantaged areas. PMID- 11204725 TI - [Clinical and epidemiological aspects of traditional therapeutic scarification in epilepsy in Togo]. AB - One of the major problems of epilepsy in Africa are its social implications. Prejudice against the disease is common and epileptics are marginalised. Epilepsy is concealed from all non-family members. The very pronunciation of the word "falling disease" (as epilepsy is called) is taboo, the disease being regarded as supernatural. This unfavourable context introduces considerable bias in hospital and population-based studies. Traditional doctors are consulted by patients especially when they have such a "supernatural" disease. Traditional scarifications are used for the treatment of epileptics in Togo. We examined the skin of 36,000 patients in the neurological department of Lome's teaching hospital between 1985 and 1995 and conducted a similar, population-based study on about 20,000 inhabitants in the Kloto district of south-western Togo and on 10,000 inhabitants in the Tone district of northern Togo. Interviews with 40,000 traditional doctors revealed that forehead scarifications are characteristic of epilepsy treatment. More than 80% of epileptics have forehead scarifications. When the seizures are rare, scarifications are slim, short (1-3 mm), near the roots of hair on the forehead and concealed; but when they are frequent, known by many people, scarifications are large, long, visible on forehead, the patient showing the sign of his social sentence.. On the skin of epileptics in Togo, is written the diagnosis of his affection. It only needs to look at it. PMID- 11204726 TI - Clinical and electro-clinical classification of epileptic seizure in west Uganda. AB - When compared to that of industralised countries, the prevalence of epilepsy in developing countries has generally been found to be higher and in some areas extremely high rates of up to 57 cases per 1000 inhabitants have been reported. The reasons for this difference are still widely unknown and detailed epidemiological as well as clinical data are scarce, especially from rural Africa. The present study was conducted in western Uganda, in an area of high epilepsy prevalence, known to be endemic for onchocerciasis. The seizures of all 91 epilepsy patients diagnosed in this area over the period of two years were classified according to the criteria of the International League against Epilepsy. Based on seizure description alone, the predominant seizure was classified as generalised in 57 patients (63%), as partial in 22 (24%) and unclassified in 12 (13%). An EEG record was analysed in 55 out of 91 patients, showing focal epileptiform activity (EA) in 12, multifocal EA in 9 and primarily generalised EA in 6 patients. When in addition to clinical information, the EEG results in the 27 patients with EA were taken in consideration for seizure classification, the proportion of partial seizures increased to 78% (n = 21); inversely the proportion of generalised seizures fell to 22% (n = 6). The predominance of partial seizures would be compatible with a localised brain lesion as a frequent cause for epileptic seizures in the study area. The findings further corroborate recent observations from several African countries of an association between epilepsy and onchocerciasis. PMID- 11204727 TI - [Stabilized epilepsy in three adult cases of pachygyria]. AB - In complex malformations of the neocortex due to neuronal migration disorders, epilepsy is usually intractable and is observed in childhood. The study of such malformations in adults is rare. Three adult cases are described with easily treated epilepsy controlled by one or two anti-epilectic drugs. A brain CAT-scan of these three patients showed pachygyria (macrogyria) sometimes associated with other malformations and disorders of neurone migration. These three 28, 40 and 53 year-old-patients (one woman and two men) were mentally disturbed with complex neurological disturbances and confined to a wheelchair. Their epilepsy had began in childhood and stabilised as these patients became adults. We raised the question as to whether this is in fact the long-term outcome for epileptic patients with pachygyria. The outcome of such epilepsy due to pachygyria could be better than initially supposed. PMID- 11204728 TI - [Questionnaire in a study of epilepsy in tropical countries]. AB - The purpose of this questionnaire is to standardize information on the epilepsy studies. It was developed through collaborative work involving the Institute of Neurological Epidemiology and Tropical Neurology of Limoges (France), the Pan African Association of Neurological Sciences and the International League Against Epilepsy (Commission on Tropical Diseases, 1993-1997). PMID- 11204729 TI - [Anti-ribosomal antibodies during hepatitis C]. AB - We report the case of a young Tunisian woman hospitalised for reasons of general ill health. A immunological check-up revealed autoimmune disturbances and in particular anti-ribosomal P antibodies. We discuss the possible relation of these antibodies to the hepatitis C infection from which the patient was also suffering. PMID- 11204730 TI - [Bacteriological and epidemiological data on Streptococcus pneumoniae in the hospital of southern Reunion Island]. AB - We studied the epidemiology of Streptococcus pneumoniae in southern Reunion Island from 1993 to 1998. Data were collected from the Centre hospitalier Sud Reunion. Incidence of pneumonia was calculated by applying published ratios to two different types of data (bacteriological, clinical). Survey of pneumococci showed that antimicrobial resistance of S. pneumoniae to penicillin G appeared in 1994 and reached high levels in 1998. We confirmed the increase of multiresistant strains among penicillin resistant S. pneumoniae. Serotyping the penicillin resistant S. pneumoniae has shown that these strains belonged to serogroups 9, 14, 19, 23. The MIC determined in PRP showed that imipenem was the most active agent among beta-lactamin antibiotics followed by ceftriaxone. Strains with high resistance to amoxicillin are rare. Annual incidence of meningitis was almost 0.4 per 100,000 inhabitants. Estimation of pneumonia incidence was between 44 and 78 per 100,000 inhabitants. Incidence in Reunion Island is twice to three times lower than the incidence in France. Death rate from pneumoniae (10%) is similar to that in France. In the course of the study, the number of isolated S. pneumoniae increased. Changing socio-economic conditions are probably associated with the emergence of PRP since 1994 and the increase in numbers of infections. Pneumococcal infections in Reunion Island are becoming a public health problem of the same importance as in France. PMID- 11204731 TI - [Esophageal tuberculosis: an unusual localization in an immunocompetent patient]. AB - Oesophageal tuberculosis is a rare localisation for extrapulmonary tuberculosis. This report describes the case of a 30-year-old immunocompetent woman with dysphagia, fever and weight loss. Endoscopic examination revealed an ulcerated lesion in the third part of the oesophagus strongly suggesting oesophageal carcinoma. Histologic samples showed epithelioid cells granuloma in the submucosa. Diagnosis was later confirmed by acid-fast bacilli positive gastric aspirates and a positive Mantoux test using the tuberculin reaction. Barium swallow revealed a narrowing in the third oesophagus. A chest x-ray revealed a infiltrated lesion and a mediastinal lymph node. The patient was put on antitubercular treatment. On follow-up after 3 months, dysphagia, fever, weight loss had disappeared and the ulcerated lesion of oesophagus had improved. The subsequent course of the patient is not known, since she was lost to follow-up. PMID- 11204732 TI - [Pulmonary amebiasis and tuberculosis association. Two case reports in Libreville, Gabon]. AB - Amoebiasis and tuberculosis are common in Gabon. International travel, cultural exchanges, changing immigration and climate of tropical provide an ideal environment for these pathogenic organisms. However, the unexpected survival of these two pathologies in the same patient is exceptional. PMID- 11204733 TI - [A 2500 year-old patient. Nosological study of a statue of the Nok culture, Nigeria]. AB - The authors describe a terra cotta statue of the Nok culture (Nigeria) dating from between 450 and 50 B. C. Amongst thousands of the same origin, this statue is the only one representing a pathological state of cirrhosis, aetiology of which may be viral, parasitological or iatrogenic. Although no precise diagnosis can be made, this statue pays tribute to the power of observation of the artist who conceived it. PMID- 11204734 TI - [Acute intoxication with "sobi-lobi" (Datura). Four cases in Niger]. AB - The datura (Datura stramonium, Datura metel) belongs to a group of plants from the solanacies variety and can be the cause of voluntary intoxication. In Nigher, its flowers and seeds are used for their hallucinogenic properties. Its alcaloids have an atropine-like effect. We are reporting here the first four cases of voluntary intoxication among teenagers in Niamey (Republic of Niger). The symptoms, which happened to be identical for the four patients, lead us quickly towards the possibility of a collective intoxication. During the questioning, the patients admitted they had smoked the plant's dried flowers, but also they drunk an herbal tea mixed with datura seeds. Symptoms are comparable to that of intoxications caused by atropine. Neurological signs are the main symptoms (agitation, delirium, disorientation, hallucination, mydriasis, retention of urine...). The others noticeable signs are: fever, dry mouth, tachycardia, thirstiness. The evolution was favourable as the patients left the hospital between D2 and D4. Those clinical features are compared to the literature items, which are inexistent in western Africa. The prognosis may be fatal, especially for the child and during massive intoxications meant to be autolystic or toxicomaniac. The recovery when possible leads usually to no sequels however sever the clinical picture is. The consultation of the population enabled us to comprehend that datura is known and consumed for its hallucinogenic proprieties. The therapeutic guidance is described and prevention suggested. PMID- 11204735 TI - [Words from the other side]. PMID- 11204736 TI - Site-specific drug delivery in the gastrointestinal tract. AB - In recent years there has been a significant increase in available strategies for site-specific delivery in the gastrointestinal tract both to maximize a therapeutic response and to reduce side effects. However, in only a few instances has there been close attention paid to how these products will perform in the heterogeneous environment of the human gut. Targeted oral delivery requires a multidisciplinary approach to research, involving contributions not only from polymer and pharmaceutical scientists but also from experts in gastroenterology and product evaluation. The objective of this article is, therefore, to examine our current understanding of human gastrointestinal physiology and to review the current "state of the art" of available targeting strategies. Emphasis will be placed on human data and, in particular, the interaction between the delivery system and the gastrointestinal tract, as assessed by product visualization studies. PMID- 11204737 TI - Enhancement of transdermal drug delivery: chemical and physical approaches. AB - Transdermal drug delivery has been intensively studied over the last two decades because of the many advantages offered by this route of administration. However, the number of drugs used in transdermal drug delivery systems has been somewhat limited, in part resulting from the formidable barrier to drug permeation presented by the upper layer of the skin, the stratum corneum. In order to overcome this, different strategies have been implemented to render the skin more permeable to drugs. These strategies include both chemical and physical approaches. In this review, we outline the enhancing activities and mechanisms of action of some of the more extensively studied chemical penetration enhancers (oxazolidinones, propylene glycol, and epidermal enzymes). In addition, we discuss novel physical strategies, such as the use of microneedles or electroporation. PMID- 11204738 TI - Expression and regulation of prostaglandin E receptor subtype mRNAs in rat sensory ganglia and spinal cord in response to peripheral inflammation. AB - Prostaglandins are known to act via seven transmembrane domain receptors to exert actions on both peripheral and central neurons resulting in changes in neuronal excitability. Prostaglandin E2, the prostaglandin most often associated with inflammation, itself acts on a family of closely related receptors, the EP receptors. Using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), we have shown that rat primary afferent neurons express the mRNA for all EP receptor subtypes, and that some, but not all EP receptor subtype mRNAs are down-regulated in sensory neurons in response to an acute peripheral inflammation. We also show for the first time that all EP receptor subtype mRNAs are expressed in rat lumbar spinal cord. Spinal cord EP receptor subtype mRNAs are also regulated in acute inflammation in a pattern distinct from the changes seen in sensory ganglia in response to the same inflammatory stimulus. PMID- 11204739 TI - Transcriptional regulation of prostaglandin-H-synthase-1 in the amnion-derived AV3 cell line. AB - Prostaglandin-H-synthase-1 (PGHS-1), while constitutively expressed in most tissues, increases in abundance in human gestational membranes at term. This suggests that PGHS-1 may be up-regulated in preparation for labor, and thus might be a key determinant in timing labor onset. We conducted transient transfection experiments in amnion-derived AV3 cells utilizing pPGHS1CAT to identify substances that might regulate PGHS-1 expression in amnion. Transforming growth factor-beta (1 ng/ml) and 15-deoxy-delta(12,14) prostaglandin J2 (1 microM) significantly (P < 0.05) (33% and 44% respectively) increased PGHS-1 promoter activity. The activity decreased significantly (P < 0.05) in response to interleukin-1 (IL-1)beta (1 ng/ml) (45%), tumor necrosis factor (TNF)-alpha (50 ng/ml) (34%), epidermal growth factor (10 ng/ml) (54%), phorbol myristate acetate (10 nM) (70%), IL-4 (10 ng/ml) (50%), IL-8 (100 ng/ml) (72%) and Activin A (25 ng/ml) (32%). Whether this degree of change in promoter activity leads to physiologically relevant alterations in the amounts of PGHS-1 present in cells remains to be determined. PMID- 11204740 TI - Growth hormone, but not luteinizing hormone, acts with luteal peptides on prostaglandin F2alpha and progesterone secretion by bovine corpora lutea in vitro. AB - Prostaglandin F2alpha (PGF2alpha) is a major physiological luteolysin in the cow. However, injection of PGF2alpha before day 5 (day 0 = estrus) of the estrous cycle dose not induce luteolysis. On the other hand, the early corpus luteum (CL) actively produces PGF2alpha. This indicates that luteal PGF2alpha may play a key role in the refractoriness to PGF2alpha injected during the early luteal phase when angiogenesis is active in the CL. Thus, this study aimed to investigate the possible interaction between pituitary hormones and local factors (luteal peptides) on secretion of PGF2alpha and progesterone (P) by the early bovine CL, and to evaluate the effect of growth hormone (GH) as well as its interactions on production of PGF2alpha in the developing CL. A RT-PCR analysis revealed that mRNA for GH receptor in CL was fully expressed from early in the luteal phase throughout the estrous cycle, while luteinizing hormone (LH) receptor mRNA was expressed less by the early and regressing CL than those at mid or late luteal phases (P < 0.05). For the stimulation test, an in vitro microdialysis system (MDS) was used as a model. Each bovine early CL (days 3-4) was implanted with the MDS, and maintained in an organ culture chamber. The infusion of GH, insulin-like growth factor-I (IGF-I) and oxytocin (OT) increased (P < 0.05) PGF2alpha and P release. In contrast, LH had no effect (P > 0.05) on PGF2alpha secretion and little effect on P release. Unexpectedly, there was no distinct interaction between pituitary hormones and luteal peptides on secretion of PGF2alpha and P. These results indicate that GH is a more powerful stimulator of PGF2alpha and P production in the early bovine CL than LH and suggest that GH and luteal peptides, IGF-1 and OT, contribute to maintenance of elevated PGF2alpha production in the developing bovine CL. PMID- 11204741 TI - Characterization of the murine epidermal 12/15-lipoxygenase. AB - The murine lipoxygenase (LO) family consists of at least seven members classified according to the HETE (hydroxyeicosatetraenoic acid) metabolite generated during arachidonic acid metabolism and the site of tissue expression. At present there are four 12-lipoxygenases that are functionally distinct, vary in cell and tissue distribution, catalytic activity and each are products of separate, linked genes. They are "platelet-type" 12-LO (P-12LO), "leukocyte-type" 12-LO (L-12LO), "epidermal-type" 12-LO (e-12LO) and the most recently discovered 12(R)-LO. In this report we characterize e-12LO, which was overexpressed in the baculovirus/insect cell expression system. The enzyme functions as a dual specificity 12/15-lipoxygenase with a 12-HETE/15-HETE product ratio of approximately 6:1 with arachidonic acid as substrate. Several other polyunsaturated fatty acids served as substrates for e-12LO such as gamma linolenic, dihomo-gamma-linolenic and eicosapentaenoic acids. A green fluorescent protein/e-12LO fusion protein was localized to the cytosol of transfected HEK 293 cells. The e-12LO gene was expressed in mouse oocytes and early embryos. Western blot analysis revealed high level expression in postnatal day 3 mouse epidermal lysates. Together these data suggest that e-12LO plays a role in normal epidermal function and as yet an undiscovered role in early development. PMID- 11204742 TI - Spectrophotometric determination of benazepril in tablets. AB - A simple and sensitive spectrophotometric method has been developed for the determination of benazepril HCl in pharmaceutical formulations. The method is based on the reaction of the drug with potassium permanganate in the presence of sodium hydroxide to produce a bluish-green colored species measurable at 609.4 nm. The absorbance-concentration plot is linear over the range 1-8 microg ml(-1) with minimum detectability of 0.1 microg ml(-1) (2.17 x 10(-7) M). The molar absorptivity was 4.07 x 10(4) l mol(-1) cm(-1) with correlation coefficient (n = 6) of 0.9991. The different experimental parameters affecting the development and stability of the color were studied carefully and optimized. The proposed method was applied successfully to the determination of benazepril in its dosage forms, the percentage recoveries +/- SD (n = 9) were 99.79 +/- 1.40 and 100.50 +/- 1.48 for tablets containing 10 and 20 mg, respectively. The results obtained were in good agreement with those obtained using a reference spectrophotometric method. The proposed method could be applied to the determination of benazepril in presence of the co-formulated drug, hydrochlorothiazide. A proposal of the reaction pathway was presented. PMID- 11204743 TI - Enhanced release of solid dispersions of etodolac in polyethylene glycol. AB - This work examines the release of etodolac from various molecular weight fractions of polyethylene glycol (PEG) solid dispersions. Solid dispersions of etodolac were prepared in different molar ratios of drug/carrier by using solvent and melting methods. The release rate of etodolac from the resulting complexes was determined from dissolution studies by use of USP dissolution apparatus 2 (paddle method). The physical state and drug:PEG interaction of solid dispersions and physical mixtures were characterized by X-ray diffraction (XRD), infrared spectroscopy (IR) and differential scanning calorimetry (DSC). The dissolution rate of etodolac is increased in all of the solid dispersion systems compared to that of the pure drug and physical mixtures. The solid dispersion compound prepared in the molar ratio of 1:5 by the solvent method was found to have the fastest dissolution profile. The physical properties did not change after 9 months storage in normal conditions. PMID- 11204744 TI - Synthesis of N-[4-(propyl)cyclohexyl]-amides with anti-inflammatory and analgesic activities. AB - Seventeen (un)substituted N-[4-(propyl)cyclohexyl]-amides (6a-h, 7a-h and 8) were synthesized and tested as anti-inflammatory and analgesic agents. The substituents on the aromatic ring were chosen in order to study the influence of electron-withdrawing or electron-donating residues, that change the electronic density on the aromatic moiety. The pharmacological results allow drawing some preliminary considerations on structure-activity relationships. PMID- 11204745 TI - High-performance liquid chromatography-mass spectrometric analysis of furosemide in plasma and its use in pharmacokinetic studies. AB - This study presents a rapid, specific and sensitive high-performance liquid chromatography-mass spectrometric (LC-MS) assay for the determination of furosemide in human plasma using diclofenac as an internal standard (IS). Both compounds were extracted from human plasma with ethyl acetate at pH 1 and were chromatographed using Shim-Pack GLC-CN column and a mobile phase consisting of acetonitrile and 20 mM ammonium acetate buffer solution pH 7, 4:1 (v/v) at a flow rate 1 ml min(-1). Furosemide and IS were detected by mass spectrometer operated in the negative single ion monitoring mode using APCI as an ionization process at m/z 329.2 and 294.1, respectively. The assay linearity of furosemide was confirmed over the range 50-2,000 ng ml(-1). Detection limit for furosemide in plasma was 10 ng ml(-1). The selected concentration range corresponds well with the plasma concentrations of furosemide for pharmacokinetic study. Intraday and interday relative standard deviations were 1.3-4.7 and 2.7-11.5%, respectively. The extraction recovery percentages of furosemide and IS from plasma were in the range 89.3-97.1%. The developed LC-MS procedure was applied for the determination of the pharmacokinetic parameters of furosemide after an oral administration of tablet formulation (40 mg) to two healthy male volunteers. The calculated parameters were in good agreement with the reported values. PMID- 11204746 TI - Synthesis and cytotoxic activity of 2-dialkylaminoethylamino substituted xanthenone and thioxanthenone derivatives. AB - The synthesis and biological evaluation of some new pyranoxanthenones and pyranothioxanthenones, substituted with flexible amino side-chains, and their evaluation as potential antitumor agents is described. The cytotoxic activity of the compounds and their eventual selective effect on a phase of the cell cycle were evaluated in vitro, using the murine lymphocytic L1210 leukemia cell line. The new aminoderivatives exhibited highly potent cytotoxicity against the leukemia L1210 cell line when compared to acronycine. All the compounds induced a partial accumulation of cells in the G2 + M phase of the cell cycle. PMID- 11204747 TI - Synthesis, 5-HT1A and 5-HT2A receptor affinity of new 1-phenylpiperazinylpropyl derivatives of purine-2,6- and pyrrolidine-2,5-diones. AB - Two series of 1-phenylpiperazinylpropyl derivatives 10, 11, 16, 17 and 19-24, structurally related to previously described 5-HT1A or 5-HT2A ligands 4 and 1, respectively, were synthesized and their binding properties were determined. Structural modifications which involved 1,3-diazepine ring opening in 4 (compounds 10, 11, 15, 16) and replacement of spiroalkyl moiety in 1 by aryl substituent (19-24) did not improve binding affinity and selectivity of the tested compounds. The results showed, however, that the diazepine ring present in 4 or spiroalkyl ring in 1 are important for high 5-HT1A or 5-HT2A binding affinity and selectivity of these compounds. PMID- 11204748 TI - Synthesis and microbiological activity of some N-(o-hydroxyphenyl)benzamides and phenylacetamides as the possible metabolites of antimicrobial active benzoxazoles: part II. AB - The synthesis of some N-(o-hydroxyphenyl)benzamides and benzacetamides (2a-2p) in order to determine their in vitro antimicrobial activity against two Gram positive bacteria, three Gram-negative bacteria and the fungus Candida albicans is described. The new compounds were compared with several control drugs. The derivative 2g, 4-amino-N-(o-hydroxyphenyl)benzamide, was found active at an MIC value of 25 microg/ml against the Gram-negative microorganism Klebsiella pneumoniae. Most of the compounds exhibited antibacterial activity at an MIC value of 25 microg/ml against Pseudomonas aureginosa. For the antifungal activity against C. albicans, compounds 2e, 2h and 2m were found more active than the other derivatives (MIC 12.5 microg/ml). The antimicrobial activity of some of these benzamide and phenylacetamide derivatives (2a, 2b, 2f, 2g, 2h and 2k), possible metabolites of benzoxazoles, was also compared with that of the cyclic analogues 3-8. Compound 2f possesses two dilutions better antifungal activity than its cyclic analogue the benzoxazole derivative 5 against C. albicans, while having one dilution better antibacterial activity against Streptococcus faecalis and K. pneumoniae. PMID- 11204749 TI - Dissolution tests of benazepril-HCl and hydrochlorothiazide in commercial tablets: comparison of spectroscopic and high performance liquid chromatography methods. AB - Simple, rapid and reliable spectroscopic methods (absorbance ratio and Vierordt) were compared with HPLC for quantitative determination in dissolution tests of benazepril-HCl (BNZ) and hydrochlorothiazide (HCT) in commercial tablets. A 249 nm wavelength was chosen as the isosbestic point in the absorbance ratio method, and the absorbance ratios A236/A249 nm for BNZ and A269/A249 nm for HCT were used for calculation of regression equations. For the Vierordt method, A1(1) values (%1.1 cm) obtained at 236 and 269 nm for both substances were used for quantitative analyses of BNZ and HCT. In the HPLC method, simultaneous determination of BNZ and HCT from dissolution medium was achieved using the mobile phase containing phosphate buffer (0.01 M, pH 6.2) and acetonitrile (65:35) on a Supelcocil LC-18 (4.6 x 250, 5.6 mm) reversed phase column. Dissolution tests of commercial tablets were carried out according to USP XXII paddle method in 0.1 N HCl at 50 rpm at 37 +/- 0.5 degrees C. Comparison of the dissolution data from the HPLC and two spectroscopic methods indicated that spectroscopic and HPLC methods were in good correlation with each other. Therefore, it was concluded that both spectroscopic methods as well as HPLC can be used in routine analyses of BNZ and HCT in dissolution tests of commercial tablets. PMID- 11204750 TI - Building a pharmacophore model for a novel class of antitubercular compounds. AB - Starting from a set of 32 antitubercular compounds, for the first time a three dimensional pharmacophore model has been derived through a computational approach based on CATALYST software. The model proved to be able to identify compounds belonging to classes of molecules already reported as antitubercular agents. PMID- 11204751 TI - Isolation and bioactivities of epidioxysterol from the tunicate Cynthia savignyi. AB - From a hexane extract of the tunicate Cynthia savignyi, collected in Morocco, epidioxysterol or 5,8-alpha-epidioxy-5alpha-cholest-6-en-3beta-ol has been isolated. This is the first example of epidioxysterol found in the tunicate C. savignyi. The structure of epidioxysterol has been characterised by NMR data (1H, 13C and 2D). Epidioxysterol possesses antifungal activity against three tomato pathogenic fungi: Botrytis cinerea, Fusarium oxysporum and Verticillium albo atrum and antibacterial activity against Agrobacterium tumefaciens, Escherichia coli, Staphylococcusfaecalis, Staphylococcus aureus and Pseudomonas aeruginosa and cytotoxicity against Artemia salina larvae. PMID- 11204753 TI - 4,5-Dihydroisoxazoles: testing of antimicrobial activity. AB - In the 1,3-dipolar cycloaddition of aliphatic nitrile to selected olefins, a series of 4,5-dihydroisoxazoles substituted with various functional groups, ester, carbonyl and ethereal, was obtained. These compounds were investigated for antimicrobial activity on chosen strains. PMID- 11204752 TI - O-[2-hydroxy-3-(dialkylamino)propyl]ethers of (+)-1,7,7-trimethyl bicyclo[2.2.1]heptan-2-one oxime (camphor oxime) with analgesic and antiarrhythmic activities. AB - A novel series of O-[2-hydroxy-3-(dialkylamino)propyl]ethers of (+)-camphor oxime was prepared and tested for its cardiovascular, analgesic and anti-inflammatory properties. No significant anti-inflammatory and hypotensive activities were displayed by any of the compounds, whereas several of them are reasonably active as antiarrhythmic and analgesic agents. PMID- 11204754 TI - Phytochemical study and anti-inflammatory properties of Lampaya hieronymi Schum. ex Moldenke. AB - The chemical study of aerial parts of Lampaya hieronymi Schum. ex Moldenke yielded oleanolic acid, epi-oleanolic acid, epi-maslinic acid, 4'7 dimethoxyapigenin, p-hydroxyacetophenone, and p-hydroxyacetophenone-beta glucoside. In searching for natural products as potential anti-inflammatory agents, all the compounds, except 4'7-dimethoxyapigenin were evaluated in vivo for their ability to inhibit acute inflammation. Our studies demonstrated that p hydroxyacetophenone and the triterpenes produced protective effects in carrageenan induced paw edema in mouse, at 1-3 h and 3-5 h, respectively, after the injection of carrageenan. These results indicated that their effects might correlate with the release of histamine, serotonin, kinin and prostaglandins. PMID- 11204755 TI - Anatomic and functional lesions resulting in partial or complete upper airway obstruction. PMID- 11204756 TI - Obstructive diseases of the trachea. PMID- 11204757 TI - Case of the season. Desmoplastic small round cell tumor. PMID- 11204758 TI - Bronchiectasis: current clinical and imaging concepts. PMID- 11204759 TI - HRCT of obliterative bronchiolitis and other small airways diseases. PMID- 11204760 TI - Clinical aspects of obstructive lung disease. AB - Obstructive pulmonary diseases are diverse with an extensive differential diagnosis. Most cases can be diagnosed after a systematic evaluation that includes detailed history, physical examination, routine laboratory testing, radiologic and pulmonary physiologic tests. More specific studies are indicated only in a few patients. PMID- 11204761 TI - Radiography and computed tomography of chronic obstructive pulmonary disease. PMID- 11204762 TI - Actinoplanes capillaceus sp. nov., a new species of the genus Actinoplanes. AB - Two motile actinomycete strains, K95-5561T and K95-5562, were isolated from a soil sample collected at Sayama City, Saitama Prefecture, Japan. They produced bell shaped spore vesicles (sporangia) with hairy surfaces on substrate hyphae. When released into water, the sporangiospores became motile by a tuft of polar flagella. The chemotaxonomic and morphological characteristics together with 16S rRNA gene sequence data indicated that the two isolates belonged to the genus Actinoplanes. The two strains were assigned to a single species on the basis of phenotypic, notably cultural, morphological and physiological characteristics, and DNA-DNA pairing data. The two strains were distinguished from representatives of all validly described species of Actinoplanes using a combination of genotypic and phenotypic properties. It is, therefore, proposed that strains K95-5561 and K95-5562 be recognized as a new species of the genus Actinoplanes with the name Actinoplanes capillaceus sp. nov. The type strain of the species is strain K95 5561T (=JCM 10268T =IFO 16408T). The invalidly proposed species 'Ampullariella cylindrica', 'Ampullariella pekinensis' and 'Ampullariella pilifera' were assigned to Actinoplanes capillaceus on the basis of genotypic and phenotypic data. PMID- 11204763 TI - Electron microscopy of the K2 killer effect of Saccharomyces cerevisiae T206 on a mesophilic wine yeast. AB - A mesophilic wine yeast, Saccharomyces cerevisiae CSIR Y217 K-R- was subjected to the K2 killer effect of Saccharomyces cerevisiae T206 K+R+ in a liquid grape medium. The lethal effect of the K2 mycoviral toxin was confirmed by methylene blue staining. Scanning electron microscopy of cells from challenge experiments revealed rippled cell surfaces, accompanied by cracks and pores, while those unaffected by the toxin, as in the control experiments, showed a smooth surface. Transmission electron microscopy revealed that the toxin damaged the cell wall structure and perturbed cytoplasmic membranes to a limited extent. PMID- 11204764 TI - Phylogenetic analysis of Bacillus subtilis and related taxa based on partial gyrA gene sequences. AB - Partial gyrA sequences were determined for twelve strains belonging to Bacillus amyloliquefaciens, B. atrophaeus, B. licheniformis, B. mojavensis, B. subtilis subsp. subtilis, B. subtilis subsp. spizizenii and B. vallismortis. The average nucleotide and translated amino acid similarities for the seven type strains were 83.7 and 95.1%, respectively, whereas the corresponding value for the 16S rRNA sequences was 99.1%. All of the type strains were sharply separated; the closest relationship was found between B. atrophaeus and B. mojavensis which shared a nucleotide similarity of 95.8%. Phylogenetic trees were inferred from gyrA nucleotide sequences using the neighbor-joining, Fitch-Margoliash and maximum parsimony algorithms. The test strains were divided into four groups, which generally reflected results previously reported in restriction digest and DNA-DNA hybridization studies. It is concluded from the comparative sequence analysis that the gyrA sequences provide a firm framework for the rapid and accurate classification and identification of Bacillus subtilis and related taxa. PMID- 11204765 TI - Screening of basidiomycetes for antimicrobial activities. AB - As a part of a screening programme developed to evaluate the antimicrobial activity of basidiomycetes, 317 isolates representing 204 species collected in Spain were screened against a range of human clinical pathogens and laboratory controls. Extracts from 45% of the isolates, representing 109 species, showed antimicrobial activity. Antibacterial activity was more pronounced than antifungal activity. The proportion of extracts from basidiomycetes showing antimicrobial activity was similar to or above that obtained for representative orders of Ascomycetes, such as Pezizales and Xylariales, but lower than that produced by members of the orders Diaporthales, Eurotiales, Hypocreales, Leotiales and Sordariales. Suprageneric taxa (orders and families) did not show pronounced differences in their antimicrobial activities though such differences were observed at the genus level, suggesting that the ability to produce these bioactive compounds is not homogenously distributed amongst the basidiomycetes. Isolates from some species showed large differences in their ability to produce metabolites with antimicrobial activity, possibly reflecting genetic differences at the infraspecific level. PMID- 11204766 TI - Characterization by molecular cloning and sequencing of the gene encoding an aminopeptidase from Listeria monocytogenes. AB - The pepC gene of Listeria monocytogenes encodes aminopeptidase C that is predicted to share 72% amino acid sequence similarity and 53% sequence identity with the cysteine aminopeptidase PepC from Lactococcus lactis. The gene product also shows strong similarity to aminopeptidase C from Streptococcus thermophilus and Lactobacillus helveticus, and to a cysteine proteinase/bleomycin hydrolase from Saccharomyces cerevisiae. The enzyme from L. monocytogenes displayed broad N terminal hydrolytic activity, with a similar substrate specificity to its lactic acid bacterial counterpart. The inhibition spectrum shows a great deal of similarity with enzymes from the family of lactic acid bacteria. In addition, one of the clones studied contained DNA sequences that could encode a regulatory protein of the deoR helix-turn-helix DNA binding protein family. The organization of the locus, designated pep, is presented along with the characterization of the gene products of the pep locus. PMID- 11204767 TI - Exserohilum israeli, a new species isolated from soil from Timna Park (Israel), and its physiological properties. AB - Fungi isolated from soil in Timna Park (Israel) were found to belong to a new species of Exserohilum for which the name Erserohilum israeli sp. nov. is proposed. The main physiological properties of members of this species are discussed and the influence of temperature and copper concentrations on the growth and morphology of the fungus were investigated. PMID- 11204768 TI - Synergistic effects of low doses of histatin 5 and its analogues on amphotericin B anti-mycotic activity. AB - The increase in the use of antifungal agents for prophylaxis and therapy has led to the development of antifungal drug resistance. Drug combinations may prevent or delay resistance development. The aim of the present study was to investigate whether naturally and designed cationic antifungal peptides act synergistically with commonly used antimycotics. No enhanced activity was found upon addition of dhvar4, a designed analogue of the human salivary peptide histatin 5, or PGLa to fluconazole or 5-flucytosine, respectively. In contrast, strong synergism of amphotericin B with the peptides was found against several Aspergillus, Candida, and Cryptococcus strains, and against an amphotericin B-resistant C. albicans laboratory mutant in the standardised broth microdilution assays according to the NCCLS standard method M27-T. Amphotericin B showed synergism with dhvar5, another designed analogue of histatin 5, and with magainin 2 against all seven tested strains. Combinations of amphotericin B with histatin 5, dhvar4, and PGLa showed synergism against four of the seven strains. The growth inhibitory activity of amphotericin B was enhanced by sub-MIC concentrations of peptide, but its haemolytic activity remained unaffected, suggesting that its cytotoxicity to host cells was not increased and that peptides may be suitable candidates for combination therapy. PMID- 11204769 TI - Application of a method incorporating differential centrifugation for selective isolation of motile actinomycetes in soil and plant litter. AB - The present paper describes a simple enrichment technique which enables rapid and selective isolation of diverse zoosporic actinomycete genera directly from soil and plant litter. This technique, designated the rehydration and centrifugation (RC) method, consists of immersing the air-dried source material in 10 mM phosphate buffer containing 10% soil extract, letting the preparation stand at 30 degrees C for 90 min, followed by centrifugation of the fluid at 1,500 x g for 20 min. Portions of the supernatant containing actinomycete zoospores are plated on the humic acid-vitamin agar which is supplemented with nalidixic acid and trimethoprim as the selective inhibitors for Gram-negative bacteria and bacilli. The phosphate buffer-soil extract solution significantly promoted liberation of motile zoospores from the source material. The centrifugation stage greatly eliminated streptomycetes and other non-motile actinomycetes from the liquid phase, thereby facilitating selective growth of rare, motile actinomycetes on the isolation plates subsequent to inoculation. Ten different soil and leaf-litter samples, taken from fields, forests, and stream banks, were examined. The RC method consistently achieved preferential isolation of motile actinomycetes in all samples, which accounted for 37-86% of the total microbial population recovered. The most frequently isolated motile actinomycetes were Actinoplanes and Dactylosporangium. Strains of Actinokineospora, Catenuloplanes and Kineosporia were also recovered, depending on the nature of the samples examined. Other motile actinomycetes that were occasionally isolated in small numbers included Actinosynnema, Geodermatophilus and Sporichthya. PMID- 11204770 TI - Pseudohyphal growth is induced in Saccharomyces cerevisiae by a combination of stress and cAMP signalling. AB - In Saccharomyces cerevisiae pseudohyphae formation may be triggered by nitrogen deprivation and is stimulated by cAMP. It was observed that even in a medium with an adequate nitrogen supply, cAMP can induce pseudohyphal growth when S. cerevisiae uses ethanol as carbon source. This led us to investigate the effects of the carbon source and of a variety of stresses on yeast morphology. Pseudohyphae formation and invasive growth were observed in a rich medium (YP) with poor carbon sources such as lactate or ethanol. External cAMP was required for the morphogenetic transition in one genetic background, but was dispensable in strain sigma 1278b which has been shown to have an overactive Ras2/cAMP pathway. Pseudohyphal growth and invasiveness also took place in YPD plates when the yeast was subjected to different stresses: a mild heat-stress (37 degrees C), an osmotic stress (1 m NACl), or addition of compounds which affect the lipid bilayer organization of the cell membrane (aliphatic alcohols at 2%) or alter the glucan structure of the cell wall (Congo red). We conclude that pseudohyphal growth is a physiological response not only to starvation but also to a stressful environment; it appears to require the coordinate action of a MAP kinase cascade and a cAMP-dependent pathway. PMID- 11204771 TI - Characterisation of a lipomannan lipoglycan from the mycolic acid containing actinomycete Dietzia maris. AB - Lipoglycans such as the mycobacterial lipoarabinomannans (LAM) are important cell envelope components of actinomycetes. To further our understanding of the diversity of these enigmatic macromolecules the lipoglycan composition of Dietzia maris has been investigated. Phenol-water extraction and hydrophobic interaction chromatography were used to purify a lipoglycan which was unusually small and predominantly lipomannan in nature. The presence of minor levels of arabinose along with components consistent with the presence of a phosphatidylinositol anchor suggest that this lipoglycan is a novel representative of the lipomannan/LAM structural archetype. This was further supported by the observed cross-reaction of the D. maris lipoglycan with an antiserum raised against LAM from Mycobacterium tuberculosis. These findings reveal a previously unsuspected diversity in the lipoglycan composition of the mycolic acid containing actinomycetes and are further discussed in relation to the apparent absence of phosphatidylinositolmannoside glycolipids in D. maris. PMID- 11204772 TI - Sibling differences in cell death of the fission yeast, Schizosaccharomyces pombe, exposed to stress conditions. PMID- 11204774 TI - PTK1, a mitogen-activated-protein kinase gene, is required for conidiation, appressorium formation, and pathogenicity of Pyrenophora teres on barley. AB - Mitogen-activated protein kinases (MAPKs) are a group of protein kinases that execute a wide variety of roles in cellular signal transduction pathways such as osmoregulation, cell wall biosynthesis, growth, and differentiation. A polymerase chain reaction (PCR) with degenerate primers based on conserved regions of known MAPKs was used to clone the MAPK gene PTK1 from the leaf pathogen Pyrenophora teres (anamorph Drechslera teres), the causal agent of net blotch of barley (Hordeum vulgare L.). The predicted amino acid sequence shows high homology with MAPKs from other phytopathogenic fungi. The gene is present in the genome as a single copy. PTK1 is expressed during in vitro growth on complete medium, under conidiation-inducing conditions and during infection of barley leaves, as shown by reverse transcription-PCR studies. In order to assess the role of PTK1 in the life cycle of P. teres, targeted gene disruption was conducted. Mutants carrying an interrupted copy of the gene were deficient in conidiation, did not form appressoria on glass surfaces or on barley leaves, lost their ability to infect barley leaves, and could not colonize host tissues following artificial wounding. PMID- 11204773 TI - Production of antimicrobial defensin in Nicotiana benthamiana with a potato virus X vector. AB - A recombinant plasmid, pTXS.TH, was constructed to express the gene-encoding wasabi (Wasabia japonica) defensin with the potato virus X (PVX) vector. pTXS.TH allows the expression of defensin in the host Nicotiana benthamiana, and the defensin protein WT1 can be purified from virus-infected leaves by heat treatment and affinity chromatography. WT1 exhibits strong antifungal activity toward the phytopathogenic fungi Magnaporthe grisea (50% inhibitory concentration [IC50] = 5 microg/ml) and Botrytis cinerea (IC50 = 20 microg/ml) but is weakly active against the phytopathogenic bacterium Pseudomonas cichorii. This virus-mediated expression system is a rapid and efficient method to produce and characterize antimicrobial proteins in plants. It is particularly useful for the study of proteins that are difficult to produce with other expression systems. PMID- 11204775 TI - Tobamoviral movement protein transiently expressed in a single epidermal cell functions beyond multiple plasmodesmata and spreads multicellularly in an infection-coupled manner. AB - Cell-to-cell movement of a plant virus requires expression of the movement protein (MP). It has not been fully elucidated, however, how the MP functions in primary infected cells. With the use of a microprojectile bombardment-mediated DNA infection system for Tomato mosaic virus (ToMV), we found that the cotransfected ToMV MP gene exerts its effects in the initially infected cells and in their surrounding cells to achieve multicellular spread of movement-defective ToMV. Five other tobamoviral MPs examined also transcomplemented the movement defective phenotype of ToMV, but the Cucumber mosaic virus 3a MP did not. Together with the cell-to-cell movement of the mutant virus, a fusion between the MP and an enhanced green fluorescent protein variant (EGFP) expressed in trans was distributed multicellularly and localized primarily in plasmodesmata between infected cells. In contrast, in noninfected sites the MP-EGFP fusion accumulated predominantly inside the bombarded cells as irregularly shaped aggregates, and only a minute amount of the fusion was found in plasmodesmata. Thus, the behavior of ToMV MP is greatly modulated in the presence of a replicating virus and it is highly likely that the MP spreads in the infection sites, coordinating with the cell-to-cell movement of the viral genome. PMID- 11204776 TI - Characterization of small GTPases Cdc42 and Rac and the relationship between Cdc42 and actin cytoskeleton in vegetative and ectomycorrhizal hyphae of Suillus bovinus. AB - This work reports the isolation and molecular characterization of CDC42 and RAC1 cDNAs from the ectomycorrhiza forming filamentous homobasidiomycete Suillus bovinus. Previously, no RAC gene was described from filamentous fungi and no CDC42 gene was described from homobasidiomycetes. Southern hybridization with SbCDC42 and SbRAC1 cDNAs indicated that the S. bovinus genome contains only one CDC42 and one RAC1 gene. The predicted amino acid sequence of SbRaclp is 77% identical with the Rac1B protein of chick, whereas SbCdc42p is most identical with Schizosaccharomyces pombe Cdc42p, showing 88% identity. In the predicted amino acid sequences of SbRaclp and SbCdc42p, the five guanine nucleotide binding regions, switch I and II, and the effector domain are highly identical to those known in other small GTPases. These domain structures suggest that in S. bovinus, SbRac1p and SbCdc42p function as molecular switches regulating the organization of actin cytoskeleton, similar to yeasts and mammals. SbRAC1 and SbCDC42 were expressed in vegetative and ectomycorrhizal hyphae, and SbCdc42p was detected in ectomycorrhiza-forming hyphae if growth and differentiation of the symbiotic hyphae took place. Cdc42p and actin were localized at the tips of S. bovinus vegetative hyphae. Similar to yeast, in filamentous fungi Cdc42p may be necessary to maintain the actin cytoskeleton at hyphal tips, making the polarized growth of the hyphae possible. In developing ectomycorrhiza, Cdc42p and actin were visualized in association with plasma membrane in swollen cells typical to the symbiotic hyphae. The role of Cdc42p and actin in regulation of the growth pattern and morphogenesis of ectomycorrhizal hyphae is discussed. PMID- 11204777 TI - Functional analysis of the type III effectors AvrRpt2 and AvrRpm1 of Pseudomonas syringae with the use of a single-copy genomic integration system. AB - Gram-negative phytopathogenic bacteria require a type III secretion apparatus for pathogenesis, presumably to deliver Avr effector proteins directly into plant cells. To extend previous studies of Avr effectors that employed plasmids encoding Avr proteins, we developed a system that permits the integration of any gene into the Pseudomonas syringae genome in single copy. With this system, we confirmed earlier findings showing that P. syringae pv. maculicola strain PsmES4326 expressing the AvrRpt2 effector induces a resistance response in plants with the cognate R gene, RPS2. Chromosomally located avrRpt2, however, provoked a stronger resistance response than that observed with plasmid-expressed AvrRpt2 in RPS2+ plants. Additionally, chromosomal expression of AvrRpt2 conferred a fitness advantage on P. syringae grown in rps2- plants, aiding in growth within leaves and escape to leaf surfaces that was difficult to detect with plasmid-borne avrRpt2. Finally, with the use of the genomic integration system, we found that a chimeric protein composed of the N terminus of the heterologous AvrRpml effector and the C-terminal effector region of AvrRpt2 was delivered to plant cells. Because the C terminus of AvrRpt2 cannot translocate into plant cells on its own, this indicates that the N-terminal region can direct secretion and translocation during an infection, which supports the view that Avr proteins have a modular design. This work establishes a readily manipulatable system to study type III effectors in a biologically realistic context. PMID- 11204778 TI - Exploring infection of wheat and carbohydrate metabolism in Mycosphaerella graminicola transformants with differentially regulated green fluorescent protein expression. AB - A Mycosphaerella graminicola strain transformed with the green fluorescent protein (GFP) downstream of either a carbon source-repressed promoter or a constitutive promoter was used to investigate in situ carbohydrate uptake during penetration of the fungus in wheat leaves. The promoter region of the acu-3 gene from Neurospora crassa encoding isocitrate lyase was used as a carbon source repressed promoter. The promoter region of the Aspergillus nidulans gpdA gene encoding glyceraldehyde-3-phosphate dehydrogenase was used as a constitutive promoter. Fluorometric measurement of GFP gene expression in liquid cultures of acu-3-regulated transformants indicated that the N. crassa acu-3 promoter functions in M. graminicola as it does in N. crassa, i.e., acetate induced and carbon source repressed. Glucose, fructose, and saccharose triggered the repression, whereas mannitol, xylose, and cell wall polysaccharides did not. Monitoring the GFP level during fungal infection of wheat leaves revealed that acu-3 promoter repression occurred after penetration until sporulation, when newly differentiated pycnidiospores fluoresced. The use of GFP transformants also allowed clear visualization of M. graminicola pathogenesis. No appressoria were formed, but penetration at cell junctions was observed. These results give new insight into the biotrophic status of M. graminicola. PMID- 11204779 TI - Maize ribosome-inactivating protein inhibits normal development of Aspergillus nidulans and Aspergillus flavus. AB - The abundant maize kernel ribosome-inactivating protein 1 (RIP1) was tested for antifungal activity against Aspergillus nidulans and Aspergillus flavus. A microculture assay was developed to monitor fungal growth and development after treatment of conidia with RIP1 or control proteins. A striking decrease in hyphal proliferation was observed when conidia of A. nidulans, a genetically well characterized nonpathogenic species, were treated with RIP1 protein. Treatment with a RIP1 mutant protein that lacked enzymatic ribosome-inactivating activity caused no observable effects. RIP1 treatment of conidia from the maize pathogen A. flavus resulted in increased hyphal branching. Examination of the branched hyphae after Congo red staining revealed only one growing hyphal tip per conidium. These results indicate that both fungi were affected by RIP1 treatment, but the lysis seen with treatment of A. nidulans was apparently avoided by A. flavus. A developmental time course revealed that both fungal species were affected by RIP1 at the postdivisional growth stage. The inhibitory activity of RIP1 against normal fungal growth is consistent with a biological function to protect the seed from fungal invasion. PMID- 11204780 TI - Lotus japonicus forms early senescent root nodules with Rhizobium etli. AB - Mesorhizobium loti and Rhizobium etli are microsymbionts of the Lotus and Phaseolus spp., respectively, and secrete essentially the same Nod factors. Lotus japonicus efficiently formed root nodules with R. etli CE3, irrespective of the presence or absence of a flavonoid-independent transcription activator nodD gene. On a nitrogen-free medium, however, the host plant inoculated with R. etli showed a severe nitrogen deficiency symptom. Initially, the nodules formed with R. etli were pale pink and leghemoglobin mRNA was detectable at significant levels. Nevertheless, the nodules became greenish with time. Acetylene-reduction activity of nodules formed with R. etli was comparable with that formed by M. loti 3 weeks postinoculation, but thereafter it decreased rapidly. The nodules formed with R. etli contained much more starch granules than those formed with M. loti. R. etli developed into bacteroids in the L. japonicus nodules, although the density of bacteroids in the infected cells was lower than that in the nodules formed with M. loti. The nodules formed with R. etli were of the early senescence type, in that membrane structures were drastically disintegrated in the infected cells of the greenish nodules. Thus, L. japonicus started and then ceased a symbiotic relationship with R. etli at the final stage. PMID- 11204781 TI - Mutational analysis of the Arabidopsis RPS2 disease resistance gene and the corresponding pseudomonas syringae avrRpt2 avirulence gene. AB - Plants have evolved a large number of disease resistance genes that encode proteins containing conserved structural motifs that function to recognize pathogen signals and to initiate defense responses. The Arabidopsis RPS2 gene encodes a protein representative of the nucleotide-binding site-leucine-rich repeat (NBS-LRR) class of plant resistance proteins. RPS2 specifically recognizes Pseudomonas syringae pv. tomato strains expressing the avrRpt2 gene and initiates defense responses to bacteria carrying avrRpt2, including a hypersensitive cell death response (HR). We present an in planta mutagenesis experiment that resulted in the isolation of a series of rps2 and avrRpt2 alleles that disrupt the RPS2 avrRpt2 gene-for-gene interaction. Seven novel avrRpt2 alleles incapable of eliciting an RPS2-dependent HR all encode proteins with lesions in the C-terminal portion of AvrRpt2 previously shown to be sufficient for RPS2 recognition. Ten novel rps2 alleles were characterized with mutations in the NBS and the LRR. Several of these alleles code for point mutations in motifs that are conserved among NBS-LRR resistance genes, including the third LRR, which suggests the importance of these motifs for resistance gene function. PMID- 11204782 TI - De novo cortical cell division triggered by the phytopathogen Rhodococcus fascians in tobacco. AB - Plant growth, development, and morphology can be affected by several environmental stimuli and by specific interactions with phytopathogens. In many cases, plants respond to pathogenic stimuli by adapting their hormone levels. Here, the interaction between the phytopathogen Rhodococcus fascians and one of its host plants, tobacco, was analyzed phenotypically and molecularly. To elucidate the basis of the cell division modulation and shoot primordia initiation caused by R. fascians, tobacco plants were infected at leaf axils and shoot apices. Adventitious meristems that gave rise to multiple-shoot primordia (leafy galls) were formed. The use of a transgenic line carrying the mitotic CycB1 promoter fused to the reporter gene coding for beta-glucuronidase from Escherichia coli (uidA), revealed that stem cortical cells were stimulated to divide in an initial phase of the leafy gall ontogenesis. Local cytokinin and auxin levels throughout the infection process as well as modulation of expression of the cell cycle regulator gene Nicta;CycD3;2 are discussed. PMID- 11204783 TI - Replicase-derived resistance against pea early browning virus in Nicotiana benthamiana is an unstable resistance based upon posttranscriptional gene silencing. AB - Virus resistance in Nicotiana benthamiana plants containing a translatable Pea early browning virus (PEBV) 54K sequence from the 201K replicase gene has been reported previously. Resistant plants contain multiple transgene copies divided between two loci. Analysis of a genetic series containing the two loci in separate homozygous or heterozygous condition suggest that only one of the loci is necessary to induce the resistance. The resistance observed in R2 and R3 generations of lines containing both transgene loci in homozygous condition became less consistent in R4 and R5 generations. This inversely correlated with steady-state transgene transcript levels of the segregating populations. The use of recombinant Potato virus X vectors carrying PEBV 54K sequences showed that the resistance is based upon posttranscriptional gene silencing, is non-strand specific, and recognizes 3' located sequences within the PEBV 54K sequence. PMID- 11204784 TI - Isolation of a Xanthomonas oryzae pv. oryzae flagellar operon region and molecular characterization of flhF. AB - An 8.1-kb DNA fragment from Xanthomonas oryzae pv. oryzae that contains six open reading frames (ORF) was cloned. The ORF encodes proteins similar to flagellar proteins FlhB, FlhA, FlhF, and FliA, plus two proteins of unknown function, ORF234 and ORF319, from Bacillus subtilis and other organisms. These ORF have a similar genomic organization to those of their homologs in other bacteria. TheflhF gene product, FlhF, has a GTP-binding motif conserved in its homologs. Unlike its homologs, however, X. oryzae pv. oryzae FlhF carries two transmembrane like domains. Insertional mutations of theflhF gene with the omega cassette or the kanamycin resistance gene significantly retard but do not abolish the motility of the bacteria. Complementation of the mutants with the wild-type flhF gene restored the motility. The X. oryzae pv. oryzae FlhF interacts with itself; the disease resistance gene product XA21; and a protein homologous to the Pill protein of Pseudomonas aeruginosa, XooPilL, in the yeast two-hybrid system. The biological relevance of these interactions remains to be determined. PMID- 11204785 TI - The induction of tomato leucine aminopeptidase genes (LapA) after Pseudomonas syringae pv. tomato infection is primarily a wound response triggered by coronatine. AB - Tomato plants constitutively express a neutral leucine aminopeptidase (LAP-N) and an acidic LAP (LAP-A) during floral development and in leaves in response to insect infestation, wounding, and Pseudomonas syringae pv. tomato infection. To assess the physiological roles of LAP-A, a LapA-antisense construct (35S:asLapA1) was introduced into tomato. The 35S:asLapA1 plants had greatly reduced or showed undetectable levels of LAP-A and LAP-N proteins in healthy and wounded leaves and during floral development. Despite the loss of these aminopeptidases, no global changes in protein profiles were noted. The 35S:asLapA1 plants also exhibited no significant alteration in floral development and did not impact the growth and development of Manduca sexta and P. syringae pv. tomato growth rates during compatible or incompatible infections. To investigate the mechanism underlying the strong induction of LapA upon P. syringae pv. tomato infection, LapA expression was monitored after infection with coronatine-producing and -deficient P. syringae pv. tomato strains. LapA RNA and activity were detected only with the coronatine-producing P. syringae pv. tomato strain. Coronatine treatment of excised shoots caused increases in RNAs for jasmonic acid (JA)-regulated wound response genes (LapA and pin2) but did not influence expression of a JA-regulated pathogenesis-related protein gene (PR-1). These results indicated that coronatine mimicked the wound response but was insufficient to activate JA-regulated PR genes. PMID- 11204786 TI - Catharanthus roseus genes regulated differentially by mollicute infections. AB - A differential display of mRNAs was used to isolate periwinkle cDNAs differentially expressed following infection with one of three mollicutes: Spiroplasma citri, Candidatus Phytoplasma aurantifolia, and stolbur phytoplasma. Twenty-four differentially expressed cDNAs were characterized by Northern blots and sequence analysis. Eight of them had homologies with genes in databanks coding for proteins involved in photosynthesis, sugar transport, response to stress, or pathways of phytosterol synthesis. The regulation of these genes in periwinkle plants infected by additional phloem-restricted bacteria showed that they were not specific to a given mollicute, but correlations with particular symptoms could be established. Expression of transketolase was down regulated following infection with a pathogenic strain of S. citri. No down regulation was observed for the nonphytopathogenic mutant GMT553, which is deficient for fructose utilization. PMID- 11204787 TI - Immunogold labeling of Hrp pili of Pseudomonas syringae pv. tomato assembled in minimal medium and in planta. AB - Hypersensitive reaction and pathogenicity (hrp) genes are required for Pseudomonas syringae pv. tomato (Pst) DC3000 to cause disease in susceptible tomato and Arabidopsis thaliana plants and to elicit the hypersensitive response in resistant plants. The hrp genes encode a type III protein secretion system known as the Hrp system, which in Pst DC3000 secretes HrpA, HrpZ, HrpW, and AvrPto and assembles a surface appendage, named the Hrp pilus, in hrp-gene inducing minimal medium. HrpA has been suggested to be the Hrp pilus structural protein on the basis of copurification and mutational analyses. In this study, we show that an antibody against HrpA efficiently labeled Hrp pili, whereas antibodies against HrpW and HrpZ did not. Immunogold labeling of bacteria infected Arabidopsis thaliana leaf tissue with an Hrp pilus antibody revealed a characteristic lineup of gold particles around bacteria and/or at the bacterium plant contact site. These results confirm that HrpA is the major structural protein of the Hrp pilus and provide evidence that Hrp pili are assembled in vitro and in planta. PMID- 11204788 TI - Overcoming host- and pathogen-mediated resistance in tomato and tobacco maps to the M RNA of Tomato spotted wilt virus. AB - A viral genetic system was used to map the determinants of the ability of Tomato spotted wilt virus (TSWV) to overcome the R gene (Sw-5) in tomato and the resistance conferred by the nucleocapsid gene of TSWV (N gene) in tobacco. A complete set of reassortant genotypes was generated from TSWV isolates A and D. TSWV-A was able to overcome the Sw-5 gene in tomato and the TSWV N gene in tobacco, whereas TSWV-D was repressed by both forms of resistance. The ability to overcome both forms of resistance was associated with the M RNA segment of TSWV-A (M(A)). Overcoming the Sw-5 gene was linked solely to the presence of M(A), and the ability of M(A) to overcome the TSWV N gene was modified by the L RNA and the S RNA of TSWV-A, which is consistent with previous reports that suggest that the nucleocapsid gene is not the primary determinant for overcoming the nucleocapsid mediated resistance. Sequence analysis of the M RNA segment of TSWV-A, -D, and the type isolate BR-01 revealed multiple differences in the coding and noncoding regions, which prevented identification of the resistance-breaking nucleotide sequences. PMID- 11204789 TI - The Rhizobium etli argC gene is essential for Arginine biosynthesis and nodulation of Phaseolus vulgaris. AB - A Tn5-induced mutant strain (CTNUX5) of Rhizobium etli unable to grow with ammonium as the sole nitrogen source was isolated and characterized. Sequence analysis showed that Tn5 is inserted into an argC-homologous gene. Unlike its wild-type parent (strain CE3), the mutant strain CTNUX5 had an absolute dependency on arginine to grow. The argC gene was cloned from the wild-type strain CE3, and the resulting plasmid, pAR207, after transformation was shown to relieve the arginine auxotrophy of strain CTNUX5. Unlike strain CE3 or CTNUX5 pAR207, strain CTNUX5 showed undetectable levels of N-acetyl-gamma glutamylphosphate reductase activity. Unless arginine was added to the growth medium, strain CTNUX5 was unable to produce flavonoid-inducible lipo-chitin oligosaccharides (nodulation factors) and to induce nodules or nodulelike structures on the roots of Phaseolus vulgaris. PMID- 11204790 TI - Mucoid mutants of the biocontrol strain pseudomonas fluorescens CHA0 show increased ability in biofilm formation on mycorrhizal and nonmycorrhizal carrot roots. AB - Extracellular polysaccharides play an important role in the formation of bacterial biofilms. We tested the biofilm-forming ability of two mutant strains with increased production of acidic extracellular polysaccharides compared with the wild-type biocontrol strain Pseudomonas fluorescens CHA0. The anchoring of bacteria to axenic nonmycorrhizal and mycorrhizal roots as well as on extraradical mycelium of the arbuscular mycorrhizal fungus Glomus intraradices was investigated. The nonmucoid wild-type strain P. fluorescens CHA0 adhered very little on all surfaces, whereas both mucoid strains formed a dense and patchy bacterial layer on the roots and fungal structures. Increased adhesive properties of plant-growth-promoting bacteria may lead to more stable interactions in mixed inocula and the rhizosphere. PMID- 11204791 TI - Transient accumulation of jasmonic acid during the synchronized hypersensitive cell death in Tobacco mosaic virus-infected tobacco leaves. AB - Jasmonic acid (JA) transiently accumulated during temperature-dependent synchronous necrotic lesion formation in Tobacco mosaic virus-infected tobacco leaves. The accumulation of JA was preceded by activation of a tobacco mitogen activated protein kinase, WIPK, which functions upstream of JA in wound signal transduction pathways. PMID- 11204792 TI - Biomechanics of elastic resistance in therapeutic exercise programs. PMID- 11204793 TI - Electromyographic analysis of quadriceps fatigue after anterior cruciate ligament reconstruction. AB - STUDY DESIGN: Prospective, observational study. OBJECTIVES: To document changes in surface electromyographic activity during sustained maximum quadriceps contractions in patients before and 5 weeks after anterior cruciate ligament (ACL) reconstruction. BACKGROUND: Quadriceps weakness after injury and reconstruction of the ACL is well documented. The effect of weakness on muscle fatigue, however, is not well understood. METHODS AND MEASURES: Electromyographic signals were recorded from the vastus lateralis, vastus medialis, and rectus femoris muscles during 30-second maximum isometric contractions at 30 degrees, in 42 patients preoperatively and 5 weeks postoperatively. Signal amplitude was quantified by integrating the rectified signal (iEMG) for the initial and final 5 seconds and comparing the involved and uninvolved sides. Median frequency (MF) was computed from 4,096 point fast Fourier Transforms performed at the beginning and end of the 30-second contractions. RESULTS: Patients had moderate preoperative quadriceps weakness (16% deficit) and gross postoperative weakness (41% deficit). Weakness was associated with deficits in both MF and iEMG (r = 0.69-0.67). During the preoperative fatigue test, torque declined similarly on the involved and uninvolved sides (significant fatigue effect). During the postoperative fatigue tests, however, torque increased on the involved side and declined on the uninvolved side (significant side by fatigue interaction). For the initial 5 seconds, MF was lower on the involved than the uninvolved side but subsequently showed a smaller decline over 30 seconds preoperatively and postoperatively (significant side by fatigue interactions). IEMG was lower on the involved side preoperatively and postoperatively. During the fatigue tests, iEMG increased similarly in the involved and uninvolved sides both preoperatively and postoperatively. CONCLUSION: Quadriceps endurance exercises are not indicated after ACL reconstruction. Quadriceps weakness after ACL reconstruction was associated with fatigue resistance. Lower initial MF and smaller decline in MF during sustained contraction is consistent with fast-twitch fiber atrophy and explains fatigue resistance. PMID- 11204794 TI - Anterior tibial translation during different isokinetic quadriceps torque in anterior cruciate ligament deficient and nonimpaired individuals. AB - STUDY DESIGN: Factorial quasi-experimental design. OBJECTIVES: To quantify the effect of different levels of isokinetic concentric and eccentric knee extensor torques on the anterior tibial translation in subjects with anterior cruciate ligament (ACL) deficiency. Electromyogram (EMG) activity of 4 leg muscles was recorded in order to detect any co-activation of extensors and flexors. BACKGROUND: The rehabilitation after an ACL injury is of importance for the functional outcome of the patient. In order to construct a rehabilitation program after that injury, it is important to understand the in vivo relationships between muscle force and tibial translation. METHODS AND MEASURES: Twelve patients with unilateral ACL injury and 11 uninjured volunteers performed 36 repetitions of a quadriceps contraction at different isokinetic concentric and eccentric torque levels, on a KinCom machine (60 degrees x s(-1)), with simultaneous recordings of tibial translation (CA-4000) and EMG activity from quadriceps and hamstrings muscles. Tibial translations and EMG levels were normalized to the maximum of each subject. RESULTS: The individual anterior tibial translation increased with increased quadriceps torque in a similar manner in both quadriceps contraction modes in all legs tested. During concentric mode, translation was similar in all groups, but during eccentric mode, the mean translation was 38% larger in the ACL injured knees. No quadriceps-hamstrings co activation occurred in any test or group. CONCLUSIONS: An ACL deficient knee can limit the translation within a normal space during concentric muscle activity but not during eccentric activity. That limitation depends on other mechanisms than hamstrings co-activation. PMID- 11204795 TI - Ultrasound assessment of atherosclerotic vessel wall changes: reproducibility of intima-media thickness measurements in carotid and femoral arteries. AB - RATIONALE AND OBJECTIVES: Ultrasonography is widely used in cardiovascular research to quantify early atherosclerotic vessel wall changes. In this article, we examined the short- and long-term reproducibility of this technique in the common carotid artery, carotid bifurcation, common femoral artery, and superficial femoral artery. Furthermore, we assessed the effect of progressed atherosclerosis on reproducibility. METHODS: Repeated ultrasound examinations were performed by one observer on 15 healthy individuals and 18 patients suffering from coronary heart disease. Intima-media thickness was determined by B mode ultrasonography. The examinations were repeated by the same observer after a short time interval (short-term) and after a few weeks (long-term) and expressed as the mean difference between the measurements and the coefficient of variation (CV). RESULTS: The reproducibility of the intima-media thickness determination turned out to be best in the common carotid artery and the superficial femoral artery when performed in healthy controls (CV 5.6% and 5.5%, respectively). Reproducibility was less in patients with clinical atherosclerosis; this especially affected the reliability of the superficial femoral artery measurement (CV in healthy controls was 5.5%; in coronary heart disease patients, 17.5 %). The reliability of the intima-media thickness measurements in the common carotid artery (CV in healthy controls was 5.6%; in coronary heart disease patients, 9.5%) proved to be least affected by progressed atherosclerosis. A longer time interval between measurements did not affect the reproducibility of intima-media thickness measurements in healthy controls, whereas in the patients it led to some decrease of reproducibility and to a major decrease in reproducibility of the superficial femoral artery measurements (CV changed from 12.7% to 17.5%). CONCLUSIONS: Ultrasonography is a reliable and accurate technique to determine intima-media thickness in superficial arteries. In studies in which the intima media thickness determination is used as a marker for generalized and coronary atherosclerosis, the common carotid artery should always be included, whereas the benefit of inclusion of other arteries depends on age and the expected extent of atherosclerosis in the individuals studied. PMID- 11204796 TI - MR imaging of the small bowel with a true-FISP sequence after enteroclysis with water solution. AB - RATIONALE AND OBJECTIVES: To evaluate a novel MR enteroclysis technique for small bowel imaging. METHODS: Twenty-one patients with suspected small-bowel disease underwent both MR and conventional enteroclysis. MR enteroclysis was performed by injecting an iso-osmotic water solution through a nasojejunal catheter with a flow rate of 80 to 150 mL/min. A maximum of 2 L of water solution was administered. A dynamic heavily T2-weighted single-shot turbo spin-echo sequence was applied in coronal orientation to monitor the bowel filling and adequate distention. Twelve 4-mm-thick slices were acquired by using a true fast imaging with steady-state precession (true-FISP) sequence during an 18-second breath-hold interval. Small-bowel distention, wall conspicuity, homogeneity of opacification, and the presence of artifacts were subjectively evaluated by two reviewers using five-point scales. RESULTS: Chemical shift artifacts were low and ghost artifacts were absent. Susceptibility artifacts were more prominent in the ileum; motion artifacts were low in the jejunum, ileum, and ileocecal area. Homogeneity of opacification was very good in the jejunum, good to very good in the ileum, and good in the ileocecal area. Distention was very good to excellent in the jejunum and ileum and very good in the ileocecal area. Wall conspicuity was very good to excellent in the jejunum and ileum. CONCLUSIONS: MR enteroclysis with the true FISP sequence produced high-quality images of the small bowel. Further clinical studies are required to determine the clinical efficacy of the new technique compared with conventional enteroclysis. PMID- 11204797 TI - MR imaging of changes of the growth plate after partial physeal removal and fat graft interposition in rabbits. AB - RATIONALE AND OBJECTIVES: The most important complication of skeletal injuries involving the growth plate is growth disturbance. The purpose of this study was to evaluate MR features of growth plate modification after fat graft interposition in growth plate injury and to correlate these findings with pathological findings. METHODS: A growth plate injury model was used in 12 skeletally immature rabbits. A longitudinal drill hole 5 mm in diameter was created in the central part of the growth plate in the distal femur, bilaterally. One side was filled with autologous fat, and the contralateral defect was left empty as a control. Magnetic resonance imaging was obtained 1, 3, and 6 months after surgery, and routine histological study was performed. The authors evaluated sequential changes in MR images and the histological basis of MR findings. RESULTS: In grafted femur, the signal intensity of the grafted area was lower than that of the surrounding bone on T2-weighted images at 1 month. The growth plate defect at 3 to 6 months was modified and had a proximally tapering appearance. The ratio of the growth plate defect was smaller in the grafted femur than in the control femur after surgery. Histologically, the fat-grafted area was replaced by fibrous connective tissue. In the control femur, a bony bridge was rectangular in the longitudinal direction and showed isosignal intensity with a rim of low signal intensity on T1-weighted imaging. Histologically, the defect was filled with mature fatty marrow with new bone formation in the control femur. CONCLUSIONS: The proximally pointing appearance and the low signal intensity of the grafted area on MR suggested fibrous degeneration of grafted fat that prevented solid bony bridge formation in experimentally induced growth plate injury. PMID- 11204798 TI - Direct measurement of sound velocity in various specimens of breast tissue. AB - RATIONALE AND OBJECTIVES: Previous studies using ultrasound CT or clinical amplitude/velocity reconstruction imaging ultrasound may indicate that cancers differ from normal breast tissue by increased sound velocity. However, only limited experience with direct measurements of sound velocity exists. This study aimed to investigate sound velocity measured directly in a variety of breast specimens. METHODS: Sound velocity was measured directly by forceps in fresh breast specimens chosen to contain one type of tissue only. Eighty specimens (31 cancers, 18 benign changes of glandular/fibrous tissue, 22 fatty tissues, 5 fibroadenomas, 2 compound tissues, 1 phylloides tumor, and 1 inflammation) were analyzed. RESULTS: Ultrasound velocities in carcinoma, benign changes, fibroadenoma, inflammation, and the phylloides tumor were very similar, with almost complete overlap. In contrary, the ultrasound velocity of fatty tissue was significantly lower. Compound tissues containing fat had an intermediate sound velocity. CONCLUSIONS: Sound velocity may add complementary information to echogenicity (B-scan). Because fat lobules exhibit low ultrasound velocity and carcinomas do not, a locally exact combination of ultrasound velocity information and reflexivity information should allow improved breast cancer detection by ultrasound. PMID- 11204799 TI - Noninvasive measurement of pulmonary vascular resistances by assessment of cardiac output and pulmonary transit time. AB - RATIONALE AND OBJECTIVES: Pulmonary vascular resistance is of special interest in many diseases. Usually it is determined invasively by catheterization, but cardiac output and pulmonary transit time can be ascertained by several noninvasive methods. METHODS: Fourteen heart recipients (age 34-71 years) were examined by electron-beam CT of the heart. Cine and flow studies were performed using a total of 60 mL of contrast and a breath-hold of 20 seconds. RESULTS: A mathematical model for calculating pulmonary vascular resistances from noninvasively measured cardiac outputs and pulmonary transit times was developed. Right-sided heart catheterization served as the reference method. CONCLUSIONS: The formula created seems to allow a clinically valid estimate of pulmonary vascular resistance from noninvasively acquired data. PMID- 11204800 TI - Development of echogenic, plasmid-incorporated, tissue-targeted cationic liposomes that can be used for directed gene delivery. AB - RATIONALE AND OBJECTIVES: Echogenic antibody-conjugated anionic liposomes have been developed that allow directed tissue targeting and acoustic enhancement. These are not efficient for gene delivery. A cationic formulation that allows directed gene delivery while retaining acoustic properties may provide more efficient transfection. METHODS: Cationic liposomes were prepared and acoustic reflectivity was determined. Anti-fibrinogen-conjugated liposomes were laid on fibrin-coated slides and adherence was quantified using fluorescence techniques. Liposomes were combined with a reporter gene and plated on cell cultures. Human umbilical vein endothelial cells were stimulated to upregulate intercellular adhesion molecule-1 (ICAM-1) and were treated with anti-ICAM-1-conjugated liposomes, and gene expression was quantified. RESULTS: Cationic liposomes retained their acoustic reflectivity and demonstrated specific adherence to fibrin under flow conditions. Significant transfection of human umbilical vein endothelial cells was demonstrated, with higher gene expression seen with specific antibody-conjugated liposomes. CONCLUSIONS: Novel acoustic cationic liposomes have been developed that can be antibody conjugated for site-specific adherence and directed cell modification. This presents exciting potential for a vector that allows tissue enhancement and targeted gene delivery. PMID- 11204801 TI - MR evaluation of stent patency: in vitro test of 22 metallic stents and the possibility of determining their patency by MR angiography. AB - RATIONALE AND OBJECTIVES: To determine the extent to which visualization of intrastent anatomy in stents of different composition and design is possible by using contrast-enhanced MR angiography. METHODS: Twenty-two MR-compatible stents, most of which had a diameter of 8 mm, were positioned in a phantom filled with aqueous gadolinium solution. Coronal and axial spoiled three-dimensional gradient echo sequences were performed. Images were acquired with stents positioned at varying angulations to the main magnetic field B0. Profiles orthogonal to the stent axis allowed measurement of artifact sizes independent of window width and center. RESULTS: Oriented along B0, the Cragg, Corvita, Passager, Wallstent, Strecker, Impag, Perflex, and ZA stents allowed visualization of more than 48% of the lumen. The Memotherm, Smart, and Jostent SelfX stents showed a prominent reduction of the inner lumen to below 41%. The lumina of the covered Jostent, Palmaz, Sinus, and Symphony stents were completely obscured. The Impag, Perflex, and Strecker tantalum stents showed growing artifact sizes and a lumen reduction of at least 40% with increasing angulation to B0. CONCLUSIONS. Evaluation of the inner stent lumen by applying contrast-enhanced, three-dimensional gradient-echo sequences is not possible for the majority of stents because of their large artifacts. These depend on the stent type and orientation to B0. Even stents made of nitinol and cobalt alloys only allow qualitative patency assessment but no quantification of stenosis. PMID- 11204802 TI - Bile reflux and oesophagitis. AB - Duodenal contents, and especially bile acids and trypsin, are noxious to the oesophageal mucosa, their damaging potential depending on pH. Various methodologies have been used to measure duodenogastric or duodenogastro oesophageal reflux, all of them having technical limitations. Controversy exists as to the extent of duodenogastric reflux in GORD. Reflux of both acid and duodenal contents into the oesophagus increases with worsening of oesophagitis. Experimental data suggest that bile acids and trypsin are noxious to the oesophageal mucosa and that their damaging potential depends on pH. The injurious concentrations are, however, higher than those usually observed in the human oesophagus. Direct measurement of bile acids and trypsin is difficult and various methodologies have been used to measure duodenogastric or duodenogastro oesophageal reflux, all of them having technical limitations. Whereas available data as to the extent of duodenogastric reflux in gastro-oesophageal reflux disease (GORD) are controversial, most observations show that reflux of both acid and duodenal contents into the oesophagus increases with worsening of oesophagitis. Furthermore, acid and duodenal contents occur simultaneously in most reflux episodes. In this issue of the journal, Marshall et al. report that exposure of the gastric fundus to duodenal contents as assessed by bilirubin monitoring is similar in GORD patients with varying degrees of oesophageal mucosal injury and in healthy controls. PMID- 11204803 TI - Overexpression of co-stimulatory molecules in peripheral mononuclear cells of Helicobacter pylori-positive peptic ulcer patients: possible difference in host responsiveness compared with non-ulcer patients. AB - BACKGROUND/AIM: Helicobacter pylori is the principal cause of gastritis and peptic ulcer disease. However, H. pylori-positive patients do not always have peptic ulcer. This study was carried out in order to determine the difference in host immune reaction to H. pylori between patients with peptic ulcer and those without. METHODS: Ten H. pylori-positive patients with peptic ulcer, 10 H. pylori positive non-ulcer patients, and 10 healthy volunteers were examined for expression of surface molecules in peripheral blood mononuclear cells. The surface molecules were stained with immunofluorescence-labelled specific antibodies and analysed by flow cytometry. RESULTS: More mononuclear cells expressed molecules ICAM-1, VLA-4, Leu-M3 in H. pylori-positive ulcer patients than in non-ulcer patients and healthy volunteers. There were also more cells expressing CD28, SLe(x), CD4, HLA-DR, and NU-B2 in H. pylori-positive ulcer patients than in non-ulcer patients and healthy volunteers. There were fewer cells expressing CD8 in H. pylori-positive ulcer patients than in non-ulcer patients and healthy volunteers. CONCLUSION: H. pylori infection may cause immunological reactions which are reflected in peripheral mononuclear cells. However, the activity and characteristics of peripheral mononuclear cells, in terms of expression of adhesion molecules, may differ between ulcer and non-ulcer patients who are infected with H. pylori. PMID- 11204804 TI - Does Helicobacter pylori affect gastric mucin expression? Relationship between gastric antral mucin expression and H. pylori colonization. AB - BACKGROUND/OBJECTIVE: Helicobacter pylori colonizes the gastric mucous gel layer, the surface epithelium and glands. It has been shown that H. pylori infection causes aberrant expression of gastric mucins MUC 5 and MUC 6. This study aimed to determine the distribution of MUC 5 and MUC 6 in the gastric antrum of dyspeptic patients, and to investigate changes in this pattern in the presence of H. pylori and after successful eradication. MATERIALS AND METHODS: Gastric antrum biopsy specimens were examined by immunohistochemistry for mucin gene (MUC 5 and MUC 6) expression. Polyclonal antibodies were used to detect amino acid tandem repeats of each protein. A scoring system (0-3) was used to assess staining intensity at three sites: foveola, mucous neck cells and glands. H. pylori status was determined by histology and rapid urease test, and considered positive or negative when both tests were positive or negative, respectively. The study included 49 patients positive for H. pylori, in 36 of whom successful eradication was performed, and 11 H. pylori-negative patients. RESULTS: There was a gradient of MUC 5 expression, higher to lower, from the surface to the glands, which was more pronounced before eradication. Increased MUC 5 synthesis in the mucous neck cells and in the glands was found after H. pylori eradication (P = 0.016). MUC 6 was synthesized in the glands more than in the mucous neck cells or foveola. MUC 6 was also secreted into the lumen and probably comprised the superficial part of the unstirred mucous layer. CONCLUSION: The change in MUC 5 synthesis may reflect H. pylori colonization. PMID- 11204805 TI - Favourable effect of an acidified milk (LC-1) on Helicobacter pylori gastritis in man. AB - OBJECTIVE: The supernatant of Lactobacillus johnsonii La1 culture was shown to be bactericidal and to have a partial, acid-independent suppressive effect on Helicobacter pylori in humans. The aim of the present study was to investigate the effect of L. johnsonii La1-acidified milk (LC-1) on H. pylori infection. DESIGN AND METHODS: Fifty-three volunteers infected with H. pylori as determined by positive 13C-urea breath test and positive serology were randomized to receive either LC-1 or a placebo 180 ml twice a day for 3 weeks. All subjects also received clarithromycin 500 mg bid during the last two weeks of acidified milk therapy. Oesophagogastroduodenoscopy and biopsies were performed at inclusion and repeated 4-8 weeks after the end of the treatment. H. pylori infection was confirmed by urease test and histology. H. pylori density and inflammation were scored using a modified Sydney classification. RESULTS: LC-1 ingestion induced a decrease in H. pylori density in the antrum (P= 0.02) and the corpus (P= 0.04). LC-1 also reduced inflammation and gastritis activity in the antrum (P= 0.02 and P= 0.01, respectively) and of activity in the corpus (P= 0.02). Clarithromycin eradicated H. pylori in 26% of the subjects; LC-1 did not improve the antibiotic effect. CONCLUSION: These results suggest that H. pylori infection and gastritis can be down-regulated by LC-1. PMID- 11204807 TI - Chronic idiopathic constipation: a psychological enquiry. AB - BACKGROUND: Intractable idiopathic constipation in women is often associated with psychosocial problems. AIMS: To determine the past and current psychological factors associated with slow and normal transit constipation. PATIENTS: Twenty eight consecutive patients referred for biofeedback treatment were interviewed before the procedure. All were women. Transit studies revealed that 12 had slow transit constipation (STC) and 16 had normal transit constipation (NTC). METHODS: Patients were assessed for evidence of previous and current psychiatric diagnoses using a standardized diagnostic interview schedule. A full family and social history was noted. Self-rating scales were used to measure psychological distress, abnormal attitudes to eating and current psychosocial functioning. RESULTS: The mean age of the 28 patients was 38.2 years (SD = 10.8) with a mean duration of symptoms of 17.5 years (SD = 16.9). Seventeen (61%) had a current psychiatric disorder and 18 (64%) a previous episode of psychiatric illness. The mean age of the 16 NTC patients was 38.4 years (SD = 10.1) with a mean duration of symptoms of 12.4 years (SD = 15.9). By contrast, the 12 STC patients had a much longer mean duration of constipation (24.3 years; SD = 16.4), a mean age of 37.9 years (SD = 12.1), with half having an onset in childhood. The STC patients reported more psychosocial distress on the rating scales than those with NTC, and only one did not experience some form of adverse life event or gynaecological procedure in the 6 months before the onset of constipation. Eleven (39%) of the 28 women had had a hysterectomy at a mean age of 36 years, but only four (14%) reported a history of sexual abuse. Of the nine (32%) patients who reported markedly distorted attitudes to food, six had NTC and three had STC. CONCLUSIONS: Of consecutive patients undergoing psychological assessment for intractable constipation, three fifths had evidence of current, and two thirds a previous, affective disorder. One third reported distorted attitudes to food. Although STC is a chronic disorder accompanied by high rates of psychological distress, it does not appear to be associated with gross functional impairment. We suggest that patients who present to surgical departments with chronic intractable constipation should routinely have a psychological assessment. PMID- 11204806 TI - 123Iodine-labelled anti-VCAM-1 antibody scintigraphy in the assessment of experimental colitis. AB - OBJECTIVES: To evaluate the usefulness of 123I-labelled anti-vascular cell adhesion molecule-1 (VCAM-1) monoclonal antibody (MAb) scintigraphy in the assessment of colonic inflammatory damage. DESIGN: Colitis was induced by intracolonic administration of 30 mg trinitrobenzenesulphonic acid in 0.5 ml of 50% (v/v) ethanol. Rats injected with vehicle served as controls. Animals were studied at day 7 after induction of colitis. METHODS: Scintigraphy was performed in control and trinitrobenzenesulphonic acid-induced colitic rats 2, 4 and 24 h after intravenous administration of 123I-anti-VCAM-1 MAb. Scintigraphic uptake was quantified in selected areas on scintigraphs. Animals were killed, tissue 123I radioactivity accumulation was measured, and accumulation of anti-VCAM-1 MAb in each organ was calculated. 99mTc-hexamethyl propylene amine oxime-labelled leucocyte scintigraphy was performed in additional groups of animals for comparison. RESULTS: Colonic tracer uptake was visible in scans of colitic, but not control animals. Quantification of scintigraphic uptake in the colon was significantly higher in colitic rats than in control animals (P< 0.0001). The specificity of the increase was demonstrated by lack of 123I-labelled non-binding MAb uptake in the colon, and by displacement of 123I-anti-VCAM-1 MAb colonic uptake by pre-treatment with unlabelled MAb. Accumulation of anti-VCAM-1 MAb in the colon of colitic rats was eightfold higher than in control animals. Strong correlations were found between quantification of scintigraphic uptake, anti-VCAM 1 MAb accumulation, histological damage and myeloperoxidase activity in the colon. CONCLUSION: 123I-labelled anti-VCAM-1 MAb scintigraphy allows an accurate evaluation of colonic inflammatory damage in trinitrobenzenesulphonic acid induced colitis, suggesting a potential role for this imaging technique in the assessment of human IBD. PMID- 11204808 TI - The polymorphism at position -174 of the IL-6 gene is not associated with inflammatory bowel disease. AB - OBJECTIVE: Inflammatory bowel diseases (IBD) are multifactorial disorders, characterized by failure to limit the inflammatory response to luminal antigens. Genetic factors play an important role in the pathogenesis, but little is known about the accountable genes. Increased secretion of pro-inflammatory cytokines appears crucial in the initiation of the inflammatory response. METHODS: To evaluate the role of the IL-6 gene in IBD, a functionally relevant polymorphism in the promoter region (G/C at position -174) has been genotyped in 169 patients with Crohn's disease (CD), 133 patients with ulcerative colitis (UC) and 440 healthy controls by using restriction fragment length polymorphism (RFLP) analysis. RESULTS: No significant differences were apparent in the allele, genotype and carrier frequencies between patients and controls. CONCLUSION: High secretion of IL-6 does not seem to play a major role in the genetic predisposition to IBD. PMID- 11204809 TI - Oxidative damage in alcoholic liver disease. AB - OBJECTIVE: The metabolic effects of alcohol are due both to its direct action and to that of its first metabolite, and can also be connected with the changes in redox state. Differences in ethanol distribution, bioavailability and hepatic metabolism can provide insight into the protective and predisposing factors in alcoholism, as well as gender differences of alcohol toxicity. Oxidative stress occurs following various conditions of ethanol consumption. DESIGN: Twenty-six Caucasian patients with alcoholism and 32 healthy, abstinent controls of both sexes were investigated with special regard to reduction-oxidation status and ad hoc free-radical-antioxidant balance. METHOD: Plasma free SH-group concentration, H-donating ability, and reducing power property were measured by simple spectrophotometric methods. Total scavenger capacity was determined by a newly developed chemiluminometric method in plasma and erythrocytes. RESULTS: Alcoholics showed a decrease of free SH-group concentration, hydrogen-donating ability and an increase of reducing power property in plasma. A decreased total scavenger capacity of erythrocytes and plasma of alcoholic patients, combined with gender differences, could be detected. CONCLUSIONS: Alcoholic dependence causes gradual exhaustion of the antioxidant capacity of erythrocytes, therefore this non-invasive measurement may be useful as a follow-up of the evolution of alcoholic liver disease. The results also suggest a gender susceptibility of alcohol toxicity. PMID- 11204811 TI - Diagnostic value of plasma chromogranin A in neuroendocrine tumours. AB - AIM: The aim of this study was to assess the value of plasma chromogranin A (CgA), a protein produced by neuroendocrine cells, in the diagnosis of neuroendocrine tumours. METHODS: Eighty subjects with neuroendocrine tumours were studied. Thirty-four had carcinoids, 21 nonfunctioning endocrine pancreatic tumours, 17 multiple endocrine neoplasia type 1 (MEN 1) (six of these also had gastrinomas), and eight had functioning pancreatic tumours (four gastrinomas, two glucagonomas, two somatostatinomas). Twenty-eight healthy subjects were studied as controls. A fasting plasma sample was obtained from each subject, and CgA plasma levels were measured by the ELISA method using a kit (Dako A/S, Denmark). RESULTS: In control subjects, plasma CgA values were below 5 U/l. Among the patients, 20 of the 34 with carcinoid tumours, 12 of the 21 with nonfunctioning pancreatic tumours, nine of the 17 with MEN 1 (including the six with gastrinomas), and the four gastrinomas of the eight functioning pancreatic tumours, i.e. overall, 45 of the 80 patients (56.3%) had abnormally high CgA values (22-961 U/l). Most of the patients with elevated CgA values, except nine of the 10 with gastrinomas, had multiple liver metastasis. CONCLUSIONS: The results show that the diagnostic value of plasma CgA in neuroendocrine tumours is relatively low; it may be of some interest only in patients with advanced disease and liver metastasis. Gastrinoma seems to be an exception, because in this tumour high CgA values are generally found even in the absence of liver metastasis. PMID- 11204810 TI - The extent of duodenogastric reflux in gastro-oesophageal reflux disease. AB - BACKGROUND: It is known that duodenogastro-oesophageal reflux (DGOR) increases with worsening gastro-oesophageal reflux disease (GORD). It is unclear whether this is accompanied by increasing duodenogastric reflux (DGR). OBJECTIVE: To investigate the extent of DGR in a control group and 66 patients with GORD, using the technique of ambulatory gastric bilirubin monitoring. METHODS: Sixty-six patients with reflux symptoms (30 grade 0 or 1 oesophagitis (group 1), 16 grade 2 or 3 oesophagitis (group 2), 20 Barrett's oesophagus (group 3)) and 17 healthy controls were studied. All underwent oesophageal manometry followed by 24-h ambulatory oesophageal and gastric pH monitoring and gastric bilirubin monitoring. RESULTS: Median per cent total oesophageal acid exposure (pH < 4) was significantly less in the control group (0.6%) than in group 1 (2.8%, P< 0.05) and groups 2 and 3 (7.5% and 7.8% respectively, P< 0.001). There was no significant difference between any group in median per cent total time gastric pH was greater than 4. There was no significant difference in median per cent total gastric bilirubin exposure (absorbance > 0.14) between any group. However, in each group gastric bilirubin exposure was greater in the supine position than the upright position, being significantly greater in the control group (P< 0.05) and group 1 (P < 0.001). CONCLUSIONS: Gastric bilirubin exposure is similar across the spectrum of GORD severity. It is greater in the supine than in the upright position. PMID- 11204812 TI - Gastric outlet obstruction caused by a giant gastroduodenal artery aneurysm: a case report. AB - Gastric outlet (GO) obstruction in an adult is usually caused by intrinsic gastric or duodenal lesions or pancreatic tumours. This study describes a case of a 77-year-old man who developed GO obstruction due to extrinsic compression from a large gastroduodenal artery aneurysm under rupture. This cause of GO obstruction has never previously been reported in the literature. PMID- 11204813 TI - Successful treatment of bleeding due to ileal varices in a patient with hepatocellular carcinoma. AB - This case report concerns a 62-year-old female who was known to have cirrhosis. An endoscopic examination showed no evidence of haemorrhaging due to either oesophageal or gastric varices. Angiographic studies demonstrated extravasation from the ileal varices. There was a prominent arterio-portal shunt in the liver, and the shunt was considered to be a contributing factor to induce portal hypertension and variceal bleeding in the ileum. Therefore, transcatheter arterial embolization was performed, but was unsuccessful. As a result, the patient underwent a laparotomy, and a dilatating ileocaecal vein and a communicating ovarian vein were selectively ligated. Following the procedure, the haemorrhaging stopped and she then recovered. The patient is doing well 21 months after surgery at the time of writing. PMID- 11204814 TI - Risperidone-induced cholestatic hepatitis. AB - Risperidone, a widely used atypical and potent neuroleptic drug, is assumed to induce fewer hepatic side-effects than phenothiazine anti-psychotics. Recently, we observed a case of risperidone-induced cholestatic hepatotoxicity. A 37-year old male developed a rapid increase in liver enzymes and cholestatic parameters after starting treatment with risperidone for paranoid psychosis. Work-up for other potential aetiologies was negative. The results of a percutaneous liver biopsy were consistent with drug-induced liver injury and cholestasis. Over the course of one month after the discontinuance of all anti-psychotic agents, the liver function test results returned to near-normal values. This observation supports the need to monitor cholestatic parameters in addition to liver function enzymes during initiation and the first weeks of risperidone intake. PMID- 11204815 TI - Inadvertent diclofenac rechallenge from generic and non-generic prescribing, leading to liver transplantation for fulminant liver failure. AB - This case report describes fulminant hepatic failure in a 53-year-old female caused by inadvertent rechallenging with diclofenac, treated by orthotopic liver transplantation. The case also illustrates the hazards of using both generic and non-generic drug prescribing, with drugs that are known to be toxic. The literature on non-steroidal anti-inflammatory drugs and hepatoxicity is reviewed. PMID- 11204816 TI - A case of successful management of portosystemic shunt with autosomal dominant polycystic kidney disease by balloon-occluded retrograde transvenous obliteration and partial splenic embolization. AB - We describe a patient with autosomal dominant polycystic kidney disease who was successfully managed for severe abdominal distension, impaired liver function and a portosystemic shunt by interventional therapies. The patient's intra-hepatic portal vein was compressed and narrowed by multiple liver cysts, which resulted in a decrease of the portal blood flow and portal hypertension due to a huge gastro-renal shunt These haemodynamic changes were assumed to contribute to insufficient protein synthesis in the liver. Therefore, we first repeatedly performed minocycline hydrochloride instillations to treat the multiple liver cysts. Then, we conducted a partial splenic embolization to prevent elevation of the portal vein pressure prior to balloon-occluded retrograde transvenous obliteration which was performed to increase the portal blood flow. The portal blood flow markedly increased, and protein synthesis in the liver also recovered and the clinical symptoms improved. The patient has been monitored for more than two years up to the present and her liver function parameters have remained within the normal range. Renal insufficiency is known to be a major prognostic factor in autosomal dominant polycystic kidney disease. In some cases, however, liver involvement with multiple cysts may result in a fatal outcome. In such cases, interventional therapies, as provided to this patient, should be considered. PMID- 11204817 TI - Elemental diet in the treatment of refractory coeliac disease. AB - A minority of patients with coeliac disease do not improve in spite of strictly adhering to gluten-free diet and are considered to have developed refractory disease. Such patients are usually treated with steroid and/or immunosuppressive agents but these are not without serious side effects. Herein, we present a patient with refractory coeliac disease in whom remarkable clinical and histological improvement was achieved on elemental diet. Elemental diet should be considered as a treatment option in such patients. PMID- 11204818 TI - Variceal bleeding and portal hypertensive gastropathy. AB - Cirrhosis can be the end stage of any chronic liver disease. At the time of diagnosis of cirrhosis varices are present in about 60% of decompensated and 30% of compensated patients. The risk factors for the first episode of variceal bleeding in cirrhotic patients are the severity of liver dysfunction, large size of varices and the presence of endoscopic red colour signs but only one-third of patients who have variceal haemorrhage have the above risk factors. Recent interest has been directed at identifying haemodynamic factors that may reflect the pathophysiological changes which lead to variceal bleeding, e.g. it has been confirmed that no bleeding occurs if HVPG falls below 12 mmHg and also a hypothesis has been put forward in which bacterial infection is considered a trigger for bleeding. Pharmacological treatment with beta-blockers is safe, effective and is the standard long-term treatment for the prevention of recurrence of variceal bleeding. Combination of beta-blockers with isosorbide-5 mononitrate needs further testing in randomized controlled trials. The use of haemodynamic targets for reduction in HVPG response needs further study, and surrogate markers of pressure response need evaluation. If endoscopic treatment is chosen, variceal ligation is the modality of choice. The combination of simultaneous variceal ligation and sclerotherapy does not offer any benefit. However, the use of additional sclerotherapy for the complete eradication of small varices after variceal ligation needs to be evaluated. The results of current prospective randomized controlled trials comparing variceal ligation with pharmacological treatment are awaited with great interest. Finally, the use of transjugular intrahepatic portosystemic shunt (TIPS) for the secondary prevention of variceal bleeding is not substantiated by current data, as survival is not improved and because of its worse cost-benefit profile compared to other treatments. In contrast, there still is a role for the selective surgical shunts in the modern management of portal hypertension. The ideal patients should be well compensated cirrhotics, who have had troublesome bleeding - either who have failed at least one other modality of therapy (drugs or ligation), have bled from gastric varices despite medical or endoscopic therapy, or live far from suitable medical services. Recently, ligation has been compared to beta-blockers for primary prophylaxis but so far there is no good evidence to recommend banding for primary prophylaxis, if beta-blockers can be given. PMID- 11204819 TI - Tissue restoration, tissue engineering and regenerative medicine. AB - Recently, thanks to the rapid progress of new technologies in cell modulation, extracellular matrix fabrication and synthetic polymers mimicking bodily structures, the self-regeneration of bodily defects by host tissue has been considered by many researchers. The conventional science of art in biomaterials has been concerned with restoring damaged tissue using non-biological materials such as metals, ceramics and synthetic polymers. To overcome the limitations of using such non-viable materials, several attempts to construct artificial organs mimicking natural tissue by combining modulated cells with extracellular matrix hybridized synthetic polymers have produced many worthy results with biologically functioning artificial tissues. The process involved in manufacturing biomaterials mimicking living tissue is generally called tissue engineering. However recently, the extension of knowledge about cell biology and embryology has naturally moved the focus from tissue restoration to tissue regeneration. Especially, embryonic and mesenchymal stem cells are attractive resources due to their potential for the differentiation of various tissue cells in response to signal transduction mediated by cytokines. Although no one knows yet what is the exact factor responsible for a stem cell's ability to differentiate between specific cells to generate specific tissue, what has been agreed is that delivering stem cells into the body provides a strong potential for the regeneration of tissue. In this review, the historical issues and future possibilities involved in medical tissue restoration and tissue regeneration are discussed. PMID- 11204820 TI - Tissue engineering in the twenty-first century. AB - In the 20th century, free tissue transfers have been successfully introduced using microvascular anastomosis techniques. Transplants not only include whole organs such as the kidney, liver and lung, but also bone, muscle and skin. However, there are a limited number of organs available for transplantation. This leads to the patient not only suffering from the malfunctioning tissue or organ, but also from the psychological trauma of an indefinite waiting period. The rapidly evolving field of tissue engineering is beginning to have an impact on free tissue transfers including organ. Small biopsy specimens can be grown into a large number of cells. These cultured cells can then be seeded onto biodegradable polymers, which serve several purposes. Firstly, the polymers function as a cell delivery system that enables the transplantation of a large numbers of cells into an organism. Secondly, they create a three-dimensional space for cell growth and serve as a template, thereby providing a structure for the extracellular matrix. These approaches have been demonstrated as practical strategies for the reconstruction of many tissues such as the liver, intestines, heart valve leaflets, bone and cartilage. PMID- 11204821 TI - Cellular signaling in tissue regeneration. AB - With recent progress in stem cell-based research, there has been tremendous interest in stem cell-based tissue regeneration. Stem cells can be differentiated into specialized cells/tissues by growth factors and cytokines. These small molecules are thought to play an important role in both wound healing and tissue regeneration. However, their biological activity and signal transduction during tissue regeneration are poorly understood. With recent advances in signal transduction by growth factors, the receptor kinases and G protein-coupled receptors, an understanding in the underlying mechanism of how these factors regulate tissue regeneration beginning to take place. In this review, the potential underlying mechanisms of growth factor signaling in normal tissue regeneration and chronic wound healing is discussed. Thus, it is an aim to provide a basis for designing more specific therapies for tissue regeneration in the near future. PMID- 11204822 TI - Cytokine delivery and tissue engineering. AB - Tissue engineering has been applied to various tissues, and particularly significant progress has been made in the areas of skin, cartilage, and bone regeneration. Inclusion of bioactive factors into the synthetic scaffolds has been suggested as one of the possible tissue engineering strategies. The growth factors are polypeptides that transmit signals to modulate cellular activities. They have short half-lives, for example, platelet-derived growth factor (PDGF), isolated from platelets, has a half life of less than 2 minutes when injected intravenously. Extended biological activity and the controlled release of growth factor are achieved by incorporating growth factor into the polymeric device. This review will focus on growth factor delivery for tissue engineering. Particular examples will be given whereby growth factors are delivered from a tissue-engineered device to facilitate wound healing and tissue repair. PMID- 11204823 TI - Biodegradable poly (lactic acid) microspheres for drug delivery systems. AB - In connection with aim of maximizing the bio-availability of conventional drugs with minimum side-effects, new drug delivery systems (DDS) continue to attracted much attention. The controlled or sustained release of drugs represents one such approach, and in this regard report upon a study of DDS using biodegradable polymers which include poly (lactic acid) (PLA), poly (glycolic acid), and their copolymers (PLGA). Much attention is being paid to the controlled release of bio active agents from microcapsules and microspheres made of biodegradable polymers, such as lactic acid homopolymers, as well as copolymers of glycolic acid. (11-21) Microcapsules or microspheres are injectable and able to provide pre-programmed durations of action, offering several advantages over the conventional dosage forms. This article reviews the results of a work program conducted in collaboration with a medical doctor upon DDS using biodegradable microspheres, such as PLA and PLGA. PMID- 11204824 TI - Tissue engineering a blood vessel substitute: the role of biomechanics. AB - The engineering of a functional blood vessel substitute has for a quarter of a century been a "holy grail" within the cardiovascular research community. Such a substitute must exhibit long term patency, and the critical issues in this area in many ways are influenced by biomechanics. One of the requirements is that it must be non-thrombogenic, which requires an "endothelial-like" inner lining. It also must have mechanical strength, i.e. a burst pressure, sufficient to operate at arterial pressures. Ideally, however, it must be more than this. It also must have viscoelastic properties that match those of the native vessel being replaced. Finally, if it is to be able to adapt to changing blood flow conditions, it must exhibit vasoactivity, a function which in and of itself can be viewed as biomechanical in nature. To achieve this requires having, as part of the construct, vascular smooth muscle cells, which are contractile in nature and oriented in a circumferential direction. Only if an engineered blood vessel substitute possesses all of these functional characteristics, can one say that the functionality exhibited by a native vessel is being mimicked. PMID- 11204825 TI - In vitro model of atherosclerosis using coculture of arterial wall cells and macrophage. AB - In order to determine the precise mechanism of the interactions between different types of cells, which are common phenomena in tissues and organs, the importance of coculture techniques are becoming increasingly important. In the area of cardiology, artificial arteries have been developed, based on the understanding of physiological communication of the arterial smooth muscle cells (SMC), endothelial cells (EC), and the extracellular matrix (ECM). In the study of atherosclerosis, the modification of low-density lipoprotein (LDL), which result in the recruitment and accumulation of white blood cells, especially, monocytes/macrophages, and foam cell formation, are hypothesized. Although there are well known animal models, an in vitro model of atherogenesis with a precisely known atherogenesis mechanism has not yet been developed. In this paper, an arterial wall reconstruction model using rabbit primary cultivated aortic SMCs and ECs, was shown. In addition, human peripheral monocytes were used and the transmigration of monocytes was observed by scanning electron and laser confocal microscopy. Monocyte differentiation into macrophages was shown by immunohistochemistry and comprehensive gene expression analysis. With the modified form of LDL, the macrophages were observed to accumulate lipids with a foamy appearance and differentiate into the foam cells in the ECM between the ECs and SMCs in the area of our coculture model. PMID- 11204826 TI - Art of replacing craniofacial bone defects. AB - In the history of medicine, many surgeons have been tried to reconstruct lost tissue and correct deformity, attempts to use implant materials have probably paralleled those involving autogenous tissue. Recently there has been an acceleration in the understanding of the requirements and potentials of implant materials caused by collaboration between material scientists, biomaterials engineers, clinicians, and clinical investigators. Alloplastic materials have become an essential part of reconstructing the function and contour of the craniofacial skeleton. Bone is a specialized form of connective tissue, which provides support, and protects vital and delicate organs. Bone is embryologically derived from mesenchymal tissue through membranous and endochondral ossification. In the clinical field, the need for bone graft has been increased due to trauma, tumor, craniosynostosis, and pure esthetic bone surgery. Various types of bone grafts have been used to repair craniofacial bone defects over many years, but the autogenous graft has many disadvantages, such as, limited donor sites, donor morbidity, pain, growth deformity and resorption. Many surgeons working in a number of centers around the world have created substitutes and simpler methods for bone replacement. As the alloplatic bone substitute has been advanced, many synthetic substitutes are replaced by bone in vivo over time. The ideal material should be cost effective, non-toxic, non-antigenic, non-carcinogenic, and inert in the body fluids, be easily shaped at the operating table, and maintain its desired form and consistency in situ. This article reviews several of the more commonly used materials for craniofacial reconstruction and summarizes their mechanical properties and clinical aspects. PMID- 11204827 TI - An overview of cartilage tissue engineering. AB - Articular cartilage regeneration refers to the formation of new tissue that is indistinguishable from the native articular cartilage with respect to zonal organization, biochemical composition, and mechanical properties. Due to a limited capacity to repair cartilage, scar tissue frequently has a poorly organized structure and lacks the functional characteristics of normal cartilage. The degree of success to date achieved using a purely cell- or biological-based approach has been modest. Potentially the development of a hybrid strategy, whereby, chondrocytes or chondrogenic stem cells are combined with a matrix, making cartilage in vitro, which is then subsequently transplanted, offers a route towards a new successful treatment modality. The success of this approach depends upon the material being biocompatible, processable into a suitable three dimensional structure and eventually biodegradable without harmful effects. In addition, the material should have a sufficient porosity to facilitate high cell loading and tissue ingrowth, and it should be able to support cell proliferation, differentiation, and function. The cell-polymer-bioreactor system provides a basis for studying the structural and functional properties of the cartilaginous matrix during its development, because tissue concentrations of glycosaminoglycan and collagen can be modulated by altering the conditions of tissue cultivation. PMID- 11204828 TI - Tissue-engineered human living skin substitutes: development and clinical application. AB - The skin acts as a barrier to exogenous substances, pathogens, and trauma. Skin defects caused by burns, venous ulcer, diabetic ulcer, or acute injury occasionally induce life-threatening situations. Tissue engineering provides an alternative for autologous or allogeneic tissue transplantation, which is required because of donor site limitations and the risks of transmitting infection. Currently, skin substitutes are made of only extracellular matrix, mainly cells, or combination of cells and matrices. New biotechnological approaches have led to the development of the skin equivalent, the closest match yet to native human skin in terms of histological and functional properties. This review article focuses upon the development of the in vitro and in vivo epidermis and dermis and their clinical applications. PMID- 11204829 TI - Tissue engineering of urinary organs. AB - Tissue engineering can serve as an alternative treatment for a malfunctioning or lost organ. Isolated and expanded cells adhere to a temporary scaffold, proliferate, and secrete their own extracellular matrices (ECM) replacing the biodegrading scaffold. The genitourinary system, composed of the kidney, ureter, bladder, urethra, and genital organs, is exposed to a variety of possible injury sites from the time of fetal development. All the urinary organs are mainly composed of smooth muscle and uroepithelial cells and which may be approached by tissue engineering techniques. A large number of materials, including naturally derived and synthetic polymers have been utilized to fabricate prostheses for the genitourinary system. Usually, whenever there is a lack of native urologic tissue, reconstruction is considered with native non-urologic tissue, such as, gastrointestinal segments, or skin or mucosa from multiple body sites. Engineering tissues using selective cell transplantation may provide a means to create functional new genitourinary tissues. This review concerns urinary tissues reconstructed with bladder uroepithelial cells and smooth muscle cells (SMCs) implanted on biodegradable polymer matrices. PMID- 11204830 TI - Tissue engineering applications in the genitourinary tract system. AB - The concept of cell transplantation using tissue engineering techniques has provided numerous possibilities in the area of urologic tissue reconstruction. Tissue engineering applications in the genitourinary tract system have been investigated in almost every tissue in order to improve, restore and replace existing tissue function. Although most reconstructive efforts still remain in the experimental stage, several technologies have been transferred to the bedside with satisfactory outcome. In this article, we describe tissue engineering approaches attempted in the genitourinary system for reconstruction. PMID- 11204831 TI - Temperature-Responsive surface for novel co-culture systems of hepatocytes with endothelial cells: 2-D patterned and double layered co-cultures. AB - We have developed two novel cell co-culture system, without any on cell type combination limitation, utilizing a polymer surface which is temperature sensitive with respect to its cell adhesion characteristics. One system involves a patterned co-culture of primary hepatocytes with endothelial cells utilizing patterned masked of the electron-beam cured, temperature-responsive polymer, poly (N-isopropylacrylamide) (PIPAAm) by masked electron beam irradiation. Hepatocytes were cultured to confluency at 37 degrees C on these surfaces. When the culture temperature was reduced below 32 degrees C, cells detached from the PIPAAm grafted areas without any need for trypsin. Endothelial cells were then seeded onto the same surfaces at 37 degrees C. These subsequently seeded endothelial cells adhered only to the now-exposed PIPAAm-grafted domains and could be co cultured with the hepatocytes initially seeded at 37 degrees C in well-ordered patterns. The other system involves a double layered co-culture obtained by overlaying endothelial cell sheets of the designed shape onto hepatocyte monolayers. The endothelial cells adhered and proliferated on the PIPAAm-grafted surface, as on polystyrene tissue culture dishes at 37 degrees C. By reducing the temperature, confluent monolayers of cells detached from the PIPAAm surfaces without trypsin. Because the recovered cells maintained intact cell-cell junctions together with deposited extracellular matrix, the harvested endothelial cell sheets, with designed shapes, were transferable and readily adhered to hepatocyte monolayers. Stable double layered cell sheets could be co-cultivated. These two co-culture methods enabled long-term co-culture of primary hepatocytes with endothelial cells. Hepatocytes so co-cultured with endothelial cells maintained their differentiated functions, such as albumin synthesis for unexpectedly long periods. These novel two co-culture systems offer promising techniques for basic biologic researches upon intercellular communications, and for the clinical applications of tissue engineered constructs. PMID- 11204832 TI - Re-Engineering the liver with natural biomaterials. AB - The extensive regenerative capacity of hepatocytes and the key roles of the liver in metabolic processes have generated interest in the liver as an appropriate target for cell and gene therapy. If cells were considered as natural biomaterials, then liver cell transplantation would fall within the general field of bioengineering. While unmodified hepatocytes engraft in the liver and ectopic sites, biological modifications and optimization of bioengineered systems would facilitate engraftment and survival of transplanted cells, especially in ectopic locations. Acute liver failure, chronic liver disease and metabolic deficiency states are among the conditions that can potentially be treated by cell transplantation. In acute liver failure, cell transplantation into the liver, along with the creation of an extrahepatic reservoir of cells might be required because engraftment and proliferation of transplanted cells in the liver needs time. In other situations, gradual liver repopulation alone might well be effective without additional manipulations. PMID- 11204833 TI - Transplantation of neural stem cells: cellular & gene therapy for hypoxic ischemic brain injury. AB - We have tracked the response of host and transplanted neural progenitors or stem cells to hypoxic-ischemic (HI) brain injury, and explored the therapeutic potential of neural stem cells (NSCs) injected into mice brains subjected to focal HI injury. Such cells may integrace appropriately into the degenerating central nervous system (CNS), and showed robust engraftment and foreign gene expression within the region of HI inury. They appeared to have migrated preferentially to the site of ischemia, experienced limited proliferation, and differentiated into neural cells lost to injury, trying to repopulate the damaged brain area. The transplantation of exogenous NSCs may, in fact, augment a natural self-repair process in which the damaged CNS "attempts" to mobilize its own pool of stem cells. Providing additional NSCs and trophic factors may optimize this response. Therefore, NSCs may provide a novel approach to reconstituting brains damaged by HI brain injury. Preliminary data in animal models of stroke lends support to these hypotheses. PMID- 11204834 TI - Viability evaluation of engineered tissues. AB - Biohybrid artificial organs encompass all devices capable of substituting for an organ or tissue function and are fabricated from both synthetic materials and living cells. The viability of engineered tissue could be related to the viability of implanted cells. The system of viability assay for mammalian cell culture can be applied to the determination of cell viability for engineered tissue. This review explores various methods of cell viability assay which can be applied to the viability evaluation of engineered tissue. The major criteria employed in viability assays include survival and growth in tissue culture, functional assay, metabolite incorporation, structural altercation, and membrane integrity. Each viability assay method is based on different definitions of cell viability, and has inherent advantages and disadvantages. In order to be able to assess the viability of cells with one assay method, it is desirable to compare the viability measurements from various assays derived from different criteria. PMID- 11204835 TI - Estrogen and brain function. PMID- 11204836 TI - [Prevention of fetomaternal alloimmunization]. PMID- 11204837 TI - [Prevention of fetal hemolytic disease: it is time to take action]. AB - In spite of the progress made since 1970 in specific prevention by anti-rhesus immunoglobulins, and improved management of at-risk pregnancies, allo immunization due to the erythrocytic Rh 1 antigen (formerly known as Rhesus D or Rh D) remains widespread. In fact, anti-Rh 1 antibodies currently constitute over one-third of the immune antibodies detected after pregnancy. The prevention of allo-immunization against the Rh 1 antigen is therefore still problematical, and concerns approximately one pregnant woman in seven. The etiology and pathology of fetal hemolytic disease have been recalled, and the treatment approach during pregnancy and delivery has been carefully examined. Tests for quantifying the risk of fetomaternal hemorrhage have also been described. This approach aims at improving the methods of preventing allo-immunization (e.g., during pregnancy and delivery) and the efficacy of treatment. It is also stated that if the necessary preventive action is not taken in cases of allo-immunization due to to the Rh 1 antigen, this should be considered a grave medical fault. PMID- 11204838 TI - [Hereditary polymorphonuclear neutrophil deficiencies]. AB - Rare hereditary deficiencies have been described which affect each functional stage of polymorphonuclear neutrophils. They almost invariably lead to recurrent acute infection. Among the abnormalities involving adhesion and motility, the following can be noted: the Buckley syndrome; and leucocyte type 1 and 2 adhesion deficiencies, respectively caused by a deficiency in membrane expression of beta 2 integrin CD11/CD18, and sialyl lewis X. Granulation system abnormalities include relatively non-symptomatic myeloperoxidase deficiency, specific granulation deficiency or the Chediak-Higashi syndrome with the presence of giant lysosomal granulations. Chronic or familial septic granulomatosis constitutes the main disease described due to the oxidative PMN burst connected with the functional impairment of one of the constituents of NADPH oxidase (with an incidence of one in 5.10(6) to one in 10(6) births) The transmission is X-linked, or autosomal recessive depending on the mutation. The antenatal detection of the X-linked component, gp91 phox, can be made in suspected carrier mothers. In addition to the standard treatment (Bactrim and Itraconazole), bone marrow transplantation may also be carried out, and in future gene therapy may be introduced. PMID- 11204839 TI - [Bacterial contamination of platelet concentrates by Propionibacterium acnes]. AB - In this study, three incidents of platelet contamination by Proprionibacterium acnes and an investigation of the transfusion process have been reported, which occurred at the Nord-Pas-de-Calais Blood Center over a period of several months. P. acnes is a bacterium that is present in the cutaneous flora; it does not produce any toxin, and is rarely considered as a pathogenic agent; its occurrence is widespread, in particular in those regions that are rich in sebum (face, back, scalp), and it is extremely apparent during adolescence. The three incidents occurred following the transfusion of a pool of leucodepleted platelet concentrates obtained from immunodeficient patients. The clinical outcome was in all cases positive. It was considered that the bacterial contamination of platelet concentrates could reflect insufficient skin disinfection at the site of the venipuncture and a minimal bacterial risk involving the blood collection procedure. PMID- 11204840 TI - [Laboratory testing for venous thromboembolism]. AB - Evaluation of inherited thrombophilia in patients with venous thromboembolism includes testing for functional activity of antithrombin, protein C and protein S, and resistance to activated protein C (factor V Leiden), which can be assessed with plasma and DNA-based assays. The antiphospholipid syndrome is an acquired disorder related to the development of antibodies against phospholipid-protein complexes. Testing for the antiphospholipid syndrome includes measurement of antibodies to phospholipid-protein complexes by immunoassay or by detecting interference of anti-phospholipid antibodies in sensitive phospholipid-based assays. Other genetic risk factors have been listed, including a common polymorphism in prothrombin gene (3'-untranslated region) related to an increase of prothrombin level (> 115%) and a common polymorphism in the methylene tetrahydrofolate reductase (enzyme involved in homocysteine metabolism) gene related to a mild increase of homocysteine blood level. More recently high plasmatic levels of factor VIII (> 150%) or factor XI (> 120%), not related so far to a molecular defect, have been identified as risk factors for deep vein thrombosis. As a candidate gene, factor XIII gene polymorphisms are under investigation. Beside the acquired or genetic risk factors involved in thrombophilia, the gene-environment interactions are of importance in the onset of thrombosis. PMID- 11204841 TI - [Transfusion in patients with hemoglobinopathies]. AB - A-Thalassemia involves a production deficiency concerning the synthesis of alpha globin chains, and beta-thalassemia involves the beta-globin chains. Only a few patients in France are affected by the major form of thalassemia (certain types of homozygotic beta-thalassemia). Also, the systematic screening of 'at-risk' couples and prenatal diagnosis has helped to considerably reduce the incidence of new cases. The decision to perform regular blood transfusions is made when Hb levels fall below values that are compatible with normal activity. Hb levels above 10 g/dL permit normal educational, recreational and professional activity. This level is generally maintained via a 15 mL/kg erythrocyte concentrate supplement every three weeks, or 20 mL/kg every four weeks. However, the appearance of antierythrocytic autoantibodies is possible, and this may also result in an increase in blood transfusion requirements. In intermediate thalassemia patients, residual Hb levels are maintained at between 7 and 10 g/dL, and transfusion of erythrocyte concentrates is only made in the case of aggravation of chronic anemia or when there are signs of intolerance to chronic anemia. In France, there is relatively large population of patients with sickle cell disease. Blood transfusion is a major element in the treatment of these patients. Simple transfusion is performed in cases of a lack of iron or folates, increased hemolysis, splenic sequestration or parvovirus 19 infection. The target hematocrit should mostly remain at the patient's baseline value. Exchange transfusions are not performed on a regular basis, but only in cases of stroke or other severe vaso-occlusive events, or when a patient has to be prepared for surgery. A minority of subjects are involved in chronic blood transfusion, which is used mostly to prevent cerebrovascular accidents but also in cases of cardiac, renal, or respiratory insufficiency. There is an increased prevalence of antierythrocytic alloimmunization in sickle cell patients, most probably because of the discrepancies in red cell antigens between mainly Caucasian blood donors and Afro-Caribbean recipients. PMID- 11204842 TI - [Blood transfusion audit methodology: the auditors, reference systems and audit guidelines]. AB - The audit has become an essential aspect of the blood transfusion sector, and is a management tool that should be used judiciously. The main types of audit that can be envisaged in blood transfusion are the following: operational audit concerning a predetermined activity; systems quality audit; competence audit, combining the operational audit on a specific activity with quality management, e.g., laboratory accreditation; audit of the environmental management system; and social audit involving the organization of an activity and the management of human resources. However, the main type of audit considered in this article is the conformity audit, which in this context does not refer to internal control but to conformity with an internal guideline issued by the French National Blood Service. All audits are carried out on the basis of a predescribed method (contained in ISO 10 011). The audit is a system of investigation, evaluation and measurement, and also a means of continuous assessment and therefore improvement. The audit is based on set guidelines, but in fact consists of determining the difference between the directions given and what has actually been done. Auditing requires operational rigor and integrity, and has now become a profession in its own right. PMID- 11204843 TI - Surface-bounded growth modeling applied to human mandibles. AB - From a set of longitudinal three-dimensional scans of the same anatomical structure, we have accurately modeled the temporal shape and size changes using a linear shape model. On a total of 31 computed tomography scans of the mandible from six patients, 14,851 semilandmarks are found automatically using shape features and a new algorithm called geometry-constrained diffusion. The semilandmarks are mapped into Procrustes space. Principal component analysis extracts a one-dimensional subspace, which is used to construct a linear growth model. The worst case mean modeling error in a cross validation study is 3.7 mm. PMID- 11204844 TI - Medical image segmentation using analysis of isolable-contour maps. AB - A common challenge for automated segmentation techniques is differentiation between images of close objects that have similar intensities, whose boundaries are often blurred due to partial-volume effects. We propose a novel approach to segmentation of two-dimensional images, which addresses this challenge. Our method, which we call intrinsic shape for segmentation (ISeg), analyzes isolabel contour maps to identify coherent regions that correspond to major objects. ISeg generates an isolabel-contour map for an image by multilevel thresholding with a fine partition of the intensity range. ISeg detects object boundaries by comparing the shape of neighboring isolabel contours from the map. ISeg requires only little effort from users; it does not require construction of shape models of target objects. In a formal validation with computed-tomography angiography data, we showed that ISeg was more robust than conventional thresholding, and that ISeg's results were comparable to results of manual tracing. PMID- 11204845 TI - Penalized weighted least-squares image reconstruction for dual energy X-ray transmission tomography. AB - We present a dual-energy (DE) transmission computed tomography (CT) reconstruction method. It is statistically motivated and features nonnegativity constraints in the density domain. A penalized weighted least squares (PWLS) objective function has been chosen to handle the non-Poisson noise added by amorphous silicon (aSi:H) detectors. A Gauss-Seidel algorithm has been used to minimize the objective function. The behavior of the method in terms of bias/standard deviation tradeoff has been compared to that of a DE method that is based on filtered back projection (FBP). The advantages of the DE PWLS method are largest for high noise and/or low flux cases. Qualitative results suggest this as well. Also, the reconstructed images of an object with opaque regions are presented. Possible applications of the method are: attenuation correction for positron emission tomography (PET) images, various quantitative computed tomography (QCT) methods such as bone mineral densitometry (BMD), and the removal of metal streak artifacts. PMID- 11204846 TI - Design and evaluation of a system for microscope-assisted guided interventions (MAGI). AB - The problem of providing surgical navigation using image overlays on the operative scene can be split into four main tasks--calibration of the optical system; registration of preoperative images to the patient; system and patient tracking, and display using a suitable visualization scheme. To achieve a convincing result in the magnified microscope view a very high alignment accuracy is required. We have simulated an entire image overlay system to establish the most significant sources of error and improved each of the stages involved. The microscope calibration process has been automated. We have introduced bone implanted markers for registration and incorporated a locking acrylic dental stent (LADS) for patient tracking. The LADS can also provide a less-invasive registration device with mean target error of 0.7 mm in volunteer experiments. These improvements have significantly increased the alignment accuracy of our overlays. Phantom accuracy is 0.3-0.5 mm and clinical overlay errors were 0.5-1.0 mm on the bone fiducials and 0.5-4 mm on target structures. We have improved the graphical representation of the stereo overlays. The resulting system provides three-dimensional surgical navigation for microscope-assisted guided interventions (MAGI). PMID- 11204847 TI - Maximum-likelihood transmission image reconstruction for overlapping transmission beams. AB - In many transmission imaging geometries, the transmitted "beams" of photons overlap on the detector, such that a detector element may record photons that originated in different sources or source locations and thus traversed different paths through the object. Examples include systems based on scanning line sources or on multiple parallel rod sources. The overlap of these beams has been disregarded by both conventional analytical reconstruction methods as well as by previous statistical reconstruction methods. We propose a new algorithm for statistical image reconstruction of attenuation maps that explicitly accounts for overlapping beams in transmission scans. The algorithm is guaranteed to monotonically increase the objective function at each iteration. The availability of this algorithm enables the possibility of deliberately increasing the beam overlap so as to increase count rates. Simulated single photon emission tomography transmission scans based on a multiple line source array demonstrate that the proposed method yields improved resolution/noise tradeoffs relative to "conventional" reconstruction algorithms, both statistical and nonstatistical. PMID- 11204848 TI - Surface interpolation from sparse cross sections using region correspondence. AB - The ability to estimate a surface from a set of cross sections allows calculation of the enclosed volume and the display of the surface in three-dimensions. This process has increasingly been used to derive useful information from medical data. However, extracting the cross sections (segmenting) can be very difficult, and automatic segmentation methods are not sufficiently robust to handle all situations. Hence, it is an advantage if the surface reconstruction algorithm can work effectively on a small number of cross sections. In addition, cross sections of medical data are often quite complex. Shape-based interpolation is a simple and elegant solution to this problem, although it has known limitations when handling complex shapes. In this paper, the shape-based interpolation paradigm is extended to interpolate a surface through sparse, complex cross sections, providing a significant improvement over our previously published maximal disc guided interpolation. The performance of this algorithm is demonstrated on various types of medical data (X-ray computed tomography, magnetic resonance imaging and three-dimensional ultrasound). Although the correspondence problem in general remains unsolved, it is demonstrated that correct surfaces can be estimated from a limited amount of real data, through the use of region rather than object correspondence. PMID- 11204849 TI - Accurate alignment of functional EPI data to anatomical MRI using a physics-based distortion model. AB - Mapping of functional magnetic resonance imaging (fMRI) to conventional anatomical MRI is a valuable step in the interpretation of fMRI activations. One of the main limits on the accuracy of this alignment arises from differences in the geometric distortion induced by magnetic field inhomogeneity. This paper describes an approach to the registration of echo planar image (EPI) data to conventional anatomical images which takes into account this difference in geometric distortion. We make use of an additional spin echo EPI image and use the known signal conservation in spin echo distortion to derive a specialized multimodality nonrigid registration algorithm. We also examine a plausible modification using log-intensity evaluation of the criterion to provide increased sensitivity in areas of low EPI signal. A phantom-based imaging experiment is used to evaluate the behavior of the different criteria, comparing nonrigid displacement estimates to those provided by a imagnetic field mapping acquisition. The algorithm is then applied to a range of nine brain imaging studies illustrating global and local improvement in the anatomical alignment and localization of fMRI activations. PMID- 11204851 TI - Texture analysis for classification of cervix lesions. AB - This paper presents a generalized statistical texture analysis technique for characterizing and recognizing typical, diagnostically most important, vascular patterns relating to cervical lesions from colposcopic images. The contributions of the research include: 1) the introduction of a generalized texture analysis technique based on the combination of the conventional statistical and structural textural analysis approaches by using a statistical description of geometric primitives; 2) the introduction of a set of textural measures that capture the specific characteristics of cervical textures as perceived by human. Experimental study with real images demonstrated the feasibility and promising of the proposed approach in discriminating between cervical texture patterns indicative of different stages of cervical lesions. PMID- 11204850 TI - Border detection on digitized skin tumor images. AB - A radial search technique is presented for detecting skin tumor borders in clinical dermatology images. First, it includes two rounds of radial search based on the same tumor center. The first-round search is independent, and the second round search is knowledge-based tracking. Then a rescan with a new center is used to solve the blind-spot problem. The algorithm is tested on model images with excellent performance, and on 300 real clinical images with a satisfactory result. PMID- 11204852 TI - Regularized color clustering in medical image database. AB - A regularized color clustering algorithm is proposed to solve the color clustering problem in medical image database. By incorporating both measures of cluster separability and cluster compactness, regularized color clustering allows the automatic extraction of significant color groups with varying populations. Experimental results in different color spaces show that the regularized color clustering gives superior results in extracting significant distinct/abnormal color clusters without significant increases in cluster compactness. Furthermore, results of color clustering in different color spaces show that the LUV color space is more suitable for color clustering. Methods for selecting the regularization constants have also been suggested. PMID- 11204853 TI - Microalbuminuria: prognostic marker of cardiovascular disease in essential hypertension. PMID- 11204854 TI - Methicillin-resistant Staphyloccocus aureus: evaluation of five selective media. AB - This study evaluates the performance in isolating methicillin-resistant Staphylococcus aureus (MRSA) of three media: the reduced salt formulation of mannitol salt agar plus oxacillin (MMSAO); CHROMagar Staph aureus plus ciprofloxacin (CHRAC); and Halifax MRSA medium (HMO), against the previously recommended mannitol salt agar (7% salt) plus oxacillin (OMSAO) and Baird-Parker medium plus ciprofloxacin (BPC). MRSA screening swabs were plated out onto the five selective media and the plates examined at 24 and 48 h. Suspected colonies were confirmed as MRSA by detection of heat-labile DNase, coagulase and/or protein A, and by confirming resistance to methicillin. Of 719 specimens examined, 191 grew MRSA on at least one medium. The relative sensitivities of the five media at 48 h were as follows: BPC, 94%; CHRAC, 70%; OMSAO, 61%; HMO, 56%; and MMSAO, 46%. In addition, BPC gave the least number of unnecessary investigations for non-MRSA isolates. The current advantage of BPC when performing direct culture for MRSA was confirmed. The other ciprofloxacin containing medium also produced reasonable results. Of the two mannitol salt agar media, the formulation with 7% salt gave better results. HMO proved unreliable at isolating MRSA. PMID- 11204855 TI - Effects of fish-oil constituents and plasma lipids on fibrinolysis in vitro. AB - An association between consumption of fish or fish oils and a reduction in coronary heart disease was established in the 1980s. The mechanisms underpinning this effect have been investigated extensively, with the focus on a reduction in platelet adhesiveness and a lowering of plasma concentrations of low-density lipoprotein (LDL)-cholesterol. Possible effects on fibrinolysis have received less attention and produced conflicting data. The present study evaluates such effects under chemically restricted conditions in vitro, in a system that, based on studies with haemostatically active drugs of known mechanisms, appears to have some relevance to the in vivo situation. Eicosapentaenoic acid (EPA)--one of the major constituents of fish oil--produced a statistically significant (P < 0.05) enhancement of fibrinolysis, when added before formation of the fibrin clot, but generally had the reverse effect when added afterwards. Docosahexaenoic acid (DHA)--the other major constituent of fish oil--had a dramatic inhibitory effect on clot formation, when added prior to clot formation, and inhibited lysis when added after the clot was formed. Maxepa (Seven Seas Ltd.)--a concentrate of EPA and DHA, and the pharmaceutical equivalent of fish oils--did not influence fibrinolysis, when added prior to clot formation. When added after the clot had formed, however, it produced significant (P < 0.05) and dose-dependent effects that varied from enhancement to inhibition. Similarly, both high-density lipoprotein (HDL)- and LDL-cholesterol, when added after clot formation, produced significant (P < 0.05) concentration-dependent effects that varied from enhancement of fibrinolysis (at the lower concentrations tested) to inhibition at higher concentrations. Our findings suggest that the effects of fish oil and lipids are more complex than simple enhancement or inhibition of fibrinolysis. Rather, the benefits may depend both on their concentration and whether they are present before or after the fibrin clots are formed. PMID- 11204856 TI - Protein determination in cerebrospinal fluid by protein dye-binding assay. AB - In this study, Coomassie brilliant blue (CBB) and pyrogallol red/molybdate (PRM) protein dye-binding assays for total protein determination in cerebrospinal fluid (CSF) are compared. Using human albumin (HA) as a protein calibrator, protein concentration in CSF samples (n = 73) ranged from 55-1960 mg/L (median: 315 mg/L) with the CBB assay, and from 95-2450 mg/L (median: 395 mg/L) with the PRM assay. Linear regression analysis indicated yCBB = 0.824xPRM - 8 (r = 0.99). The discrepancy between the values was investigated by comparing the response of the two assays to different proteins. Compared with HA, the PRM assay showed a more uniform response to human albumin/globulin (A/G) and bovine gamma globulin (G) than did the CBB assay, but it gave high colour yields with bovine myelin basic protein. When CSF was assayed using A/G as a protein calibrator, agreement between the methods improved (yCBB = 0.960xPRM + 0 [r = 0.99]), indicating that comparability is dictated by the choice of protein calibrator. Of the two assays studied, the PRM assay is recommended for CSF protein determination because it gives a more uniform and linear response to human albumin and globulin over a wider working range. PMID- 11204857 TI - Microalbuminuria in essential hypertension: clinical and biochemical profile. AB - This study aims to evaluate the clinical and biochemical profile associated with the presence of microalbuminuria in a group of essential hypertensive patients referred to a hypertension clinic. A total of 188 non-diabetic, untreated essential hypertensive patients (100 men, 88 women) aged 55.8 +/- 11.7 years are studied. Urinary albumin excretion was determined in two 24-h urine collections. Clinical and biochemical evaluations and 24-h ambulatory blood pressure (BP) monitoring were performed at baseline. Forty-two patients (22.3%) showed an increased urinary albumin excretion rate (20-200 micrograms/min). These patients showed significantly higher values (P < 0.01) for 24-h, daytime and night-time systolic and diastolic BP, compared with essential hypertensives with normal urinary albumin excretion. However, nocturnal reduction in BP did not differ between the groups. Furthermore, patients with microalbuminuria showed significantly higher (P < 0.01) creatinine, serum uric acid and triglycerides, as well as lower high-density lipoprotein (HDL)-cholesterol. In a multiple logistic regression analysis, a 24-h systolic BP > 140 mmHg (odds ratio: 3.19; 95% confidence interval [CI 95%]: 1.44-7.06) and a serum creatinine > 88 mumol/L (odds ratio: 3.08; CI 95%: 1.39-6.84) were the two factors associated independently with increased urinary albumin excretion. We conclude that, in essential hypertensive patients, the presence of microalbuminuria is associated with elevated BP, but not with its circadian pattern. Likewise, microalbuminuria is associated with the degree of renal impairment, and with increased uric acid and triglycerides and decreased HDL-cholesterol. PMID- 11204858 TI - Detection of the beta s gene: an evaluation of the solubility test against automated chromatography and haemoglobin electrophoresis. AB - The solubility test is evaluated against automated high-performance liquid chromatography (HPLC) and haemoglobin (Hb) electrophoresis for its efficacy in screening for the beta s gene in population groups in remote areas. Blood samples taken from 3246 individuals from the tribal populations of the Dhule and Gadchiroli districts of Maharashtra state were analysed by all three methods. The solubility test detected 871 out of 932 individuals positive for the beta s gene by HPLC and Hb electrophoresis, and showed an overall sensitivity of 93.8% and specificity of 100%, with a positive predictive value of 100% and negative predictive value of 97.4%. Both HPLC and Hb electrophoresis are relatively expensive and not available in most laboratories in remote tribal areas, where the frequency of the beta s gene is very high. We conclude that the solubility test could be used for preliminary screening to determine the prevalence of the beta s gene in different population groups, particularly in remote areas where other facilities are not available. Individuals who test positive for the beta s gene by the solubility test require further investigation by either HPLC or Hb electrophoresis. PMID- 11204859 TI - Mycoplasma detection in cell cultures: a comparison of four methods. AB - Mycoplasma is a common contaminant of tissue culture samples. Infection is persistent, difficult to detect and diagnose, and very difficult to cure. The concentration of mycoplasma in infected cultures can be as high as 10(7) colony forming units per mL, and their presence can change many of the cell reactions, including altering cell growth rate, inducing morphological changes or cell transformation, and mimicking virus infection. Therefore, it should be assumed that a mycoplasma-contaminated cell line may be significantly influenced in every respect, and, thus, experimental data derived from such a cell line is likely to be invalid. Contamination is not obvious, either macroscopically or microscopically; thus, routine mycoplasma testing is essential for any cell culture laboratory. Many of the testing procedures developed so far are time consuming, expensive, inconclusive and unsuitable for screening large numbers of test specimens. This study compares DNA staining, enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR) and PCR ELISA, to determine which is the best procedure for routine assessment of cell cultures. All four methods gave reproducible results with both infected and non-infected cell lines. Both ELISA methods were easy to perform, reproducible and easily interpreted. PMID- 11204860 TI - Internal quality control in virology: validation of immunoassays using a personal computer spreadsheet. AB - Design of a spreadsheet to evaluate the performance of internal quality control sera used for the validation of immunoassays in virology is described. Developed using Microsoft Excel 97, it can set target limits and analyse control data by application of Westgard quality control rules. It also provides a permanent record of all relevant information concerning each assay run, including action taken to rectify unacceptable performance. PMID- 11204861 TI - Vitek automated identification and susceptibility testing system: introduction into a busy clinical bacteriology laboratory. PMID- 11204862 TI - Bimodal role for divalent cations in the mechanism of EDTA cytolysis. PMID- 11204863 TI - Haemochromatosis mutation analysis in a normal Irish population. PMID- 11204864 TI - Small-colony variants of Staphylococcus aureus. AB - Staphylococcus aureus remains a versatile and dangerous pathogen. Small-colony variants (SCVs) of S. aureus are a naturally occurring sub-population, first described nearly 100 years ago. These variants, of which there are different classes, grow slowly and have many atypical characteristics thought to be due to defective electron transport, and include minute colony forms. SCVs have been isolated from sites of infection, particularly persistent recurrent ones (e.g. in chronic osteomyelitis and cystic fibrosis), and also may arise following exposure to certain antibiotics. During infection the intraendothelial-cell milieu stimulates the formation of SCVs, which can better survive the assault of cell mediated immunity. SCV phenotypes produce less tissue damage than normal staphylococci. Although microscopic morphology and Gram's staining of SCVs are normal, clinical microbiology laboratories may fail to detect them because of their very slow growth. The full extent of the role of S. aureus SCVs in clinical disease, and the most appropriate means of identifying such strains or testing to predict the clinical usefulness of therapeutic regimens, remains unknown. Failure to recover SCVs results in a major susceptibility reporting error, as the more resistant component of the infection will not have been reported. No controlled trials of therapy have been conducted, and, thus, optimal therapy has yet to be defined. However, SCVs are resistant to aminoglycoside antibiotics, and may be resistant to trimethoprim-sulphmethoxazole. The effectiveness of cell-wall-active antibiotics is reduced. SCVs are transmissible, and current infection control recommendations for normal S. aureus infections are appropriate. PMID- 11204865 TI - Diagnostic applications of cystatin C. AB - Cysteine proteases are proteolytic enzymes involved in many pathological processes and found in the lysosomes of cells; examples include the cathepsins B, H and L. The role of cysteine proteases is crucial in normal cellular metabolism, being fundamental to intracellular protein turnover, degradation of collagen, and cleaving of precursor proteins. Cysteine protease inhibitors, of which the cystatin superfamily are one example, constitute the final regulatory step in the control of cysteine proteases. Currently, cystatin C is the most frequently investigated family member and is involved in processes such as tumour invasion and metastasis, inflammatory processes and some neurological diseases. In such diseases the emphasis is placed on the fine balance and regulation of both the cysteine proteases and their inhibitors, with an imbalance resulting in a pathological state. In addition, the constant serum concentration of cystatin C means it has possible application as a replacement for creatinine in the measurement of glomerular filtration rate. To date, several assays have been developed and studies show a promising future for its use in the medical laboratory, and not just as a research tool. This review of cystatin C includes a brief history of its discovery and characterisation, provides a guide to some of the processes in which its role is fundamental, and highlights developments in its use as a clinical biomarker in the disease processes discussed. PMID- 11204866 TI - Microbiological safety cabinets: selection, installation, testing and use. AB - In the last quarter of the 20th century, there was much confusion and uncertainty amongst microbiologists and managers about the choice, installation, testing and use of the various types of microbiological safety cabinet. This review clarifies these issues, with reference to the latest standards and safe procedures. PMID- 11204867 TI - Thermus aquaticus (Taq) error rates and REP-PCR. PMID- 11204868 TI - RhD typing and the significance of Du. PMID- 11204869 TI - Fugitive discharges and waste disposal: the discussion continues. PMID- 11204870 TI - Fugitive discharges and waste disposal: the discussion continues. PMID- 11204871 TI - Time-of-day effects of ethanol consumption on EEG topography and cognitive event related potential in adult males. AB - Time-of-day effects of ethanol consumption on EEG topography and cognitive event related potential in adult males were studied. Ethanol (0.5 g/kg) or control drink was orally administered to nine healthy males at 10:00 and 18:00. The alpha 2 amplitude was significantly lower than that of the control at 0.5, 2.5 and 4.5 hours after ethanol consumption in the morning. These effects were observed in the left hemisphere and were only found after consumption in the morning. The subjectively rated attention was significantly lower than that of the control at 0.5 and 2.5 hours after ethanol consumption in the morning and at 0.5 hours after ethanol consumption in the evening. In contrast, the search speed of serial search task and P300 amplitude was significantly lower than that of the control at 2.5 hours after ethanol consumption in the evening. These results demonstrate that effects of ethanol are dependent on time-of-day of consumption. Ethanol consumption significantly lowered the alpha 2 amplitude when consumed in the morning, and lowered P300 amplitude when consumed in the evening. PMID- 11204872 TI - Autonomic response specificity during motor imagery. AB - It has been reported that activation of autonomic effectors during mental simulation of voluntary motor actions (motor imagery: MI) may be explained by two different factors, i.e., functions of preparation or anticipation of actual exercise (motor anticipation) and the central motor programming/planning which acts during actual motor action (motor programming). This study was designed to clarify how these factors participate during MI, utilizing two mental tasks with high mental stress, i.e., MI and mental arithmetic (MA). Several autonomic effectors' responses were compared between MI of a 500 m speed skating sprint and MA. Subjects were eight 18 to 25 year old young male speed skate athletes, all of them could easily and vividly imagine a 500 m speed skating sprint. Duration of the MI ranged from 35 to 38 sec and these were very close to each subject's actual best record (means of absolute differences were less than 0.6 sec, i.e., less than 1.7% relatively). A significant decrease of skin resistance (SR), increases of heart rate (HR) and respiration rate were observed in both MI and MA when compared to each control resting level (excluding one subject for respiration rate during MI). SR decreased during MI (mean and SD of 8 subjects: 45.9 +/- 17.7%) and MA (39.7 +/- 16.8%), with no significant differences between MI and MA (t = 1.29, by paired t-test). HR increased significantly above control values in MA (10.3 +/- 4.3%) and MI (44.3 +/- 18.8%). However, the increase during MA was significantly smaller (t = 4.99, p < 0.001) than in MI. Respiratory rate increased significantly in both MI (46.5 +/- 30.9%) and MA (27.7 +/- 14.6%), with no significant difference between MI and MA (t = 1.82) due to the large individual variation in MI. The frequency of respiration was fairly regular during MA, but quite irregular during MI (similar to those during actual motor actions). The central nervous system which acts in MI may possess the function of activation of target effectors which play an important role in actual exercise, on the basis of incremental vigilance level induced by the function of motor anticipation. PMID- 11204873 TI - Reliability and validity of the questionnaire to determine the biosocial rhythms of daily living in the disabled elderly. AB - The questionnaire to determine the biosocial rhythms of daily living in the disabled elderly was newly developed. This questionnaire was aimed to evaluate a state of synchronization of biological rhythms in the disabled elderly. Eighteen items of the questionnaire relating to the synchronization of biological rhythms were finally selected by the test-retest method that was conducted for 68 disabled elderly living in a community with a duration of one year. The factor analysis showed that the questionnaire consisted of five factors: outdoor activities, ultradian rhythms, subjective evaluation of health status, social support, and sleep habits. The cumulative contribution rate of five factors was 53.2%. Reliability of the questionnaire was confirmed by a calculation of the Equal-length Spearman-Brown coefficients ranging from 0.60 to 0.80. Regarding the construct validity of the questionnaire, results of factor analysis showed five factors that were consistent with the synchronizers known in chronobiology. The total score of the questionnaire was significantly correlated to Barthel Index score and the competence score, suggesting that it partly reflects the activities of daily living of the disabled elderly. We conclude that a new questionnaire to determine the biosocial rhythm of daily living in the disabled elderly is useful to evaluate the biosocial synchronization of the disabled elderly because of its high reliability and validity. PMID- 11204874 TI - Prolonged swimming exercise training induce hypophosphatemic osteopenia in stroke prone spontaneously hypertensive rats (SHRSP). AB - Stroke-prone spontaneously hypertensive rats (SHRSP) induce spontaneous osteoporosis. To elucidate the specific characteristics of bone metabolism, the SHRSP was compared with age matched Wistar-Kyoto (WKY) rats. We investigated the effects of prolonged swimming exercise training on bone mineral density (BMD) and metabolism in the SHRSP. Seven-week-old male SHRSP and WKY were divided into three groups; the sedentary control WKY group (n = 6, WKY), the sedentary control SHRSP group (n = 6, SP) and the swimming exercise training SHRSP group (n = 6, SWIM) (in pool with 60 min./day, 5 days/week for 12 weeks). The femoral BMD, bone mineral content (BMC), strength, Ca and P contents (%) of SHRSP were approximately 17, 27, 25, 20 and 9%, respectively, lower than that of WKY (p < 0.001). Serum alkaline phosphatase (AlP) had not changed between both of SP and WKY, but tartrate-resistant acid phosphatase (TrAcP) of SP approximately 3-fold higher than that of WKY (p < 0.05). Both serum calcium (Ca) and intact parathyroid hormone (i-PTH) were similar between SP and WKY. However, serum phosphate (P) of SP was approximately 18% lower than that of WKY (N.S.). These results suggested that SHRSP induces osteopenia by the bone turnover of the promoted osteoclast activity with disturbed phosphate homeostasis. On the other hand, the femoral BMD and strength were approximately 7% and 20%, respectively, decreased in the SWIM (p < 0.001), and femoral bone Ca and P contents (%) were also approximately 11% and 14%, respectively, lower than that of SP (p < 0.001). There were no significant difference between SWIM and SP on serum Ca, but serum P of SWIM was significantly lower than that of SP (p < 0.05). These results suggested that the prolonged swimming exercise training in the SHRSP induces more cruelly hypophosphatemia, and leading to osteopenia eventually. We conclude that SHRSP induces osteopenia with disturbance of phosphate homeostasis, and the prolonged swimming exercise in the SHRSP might deteriorate hypophosphatemia and osteopenia. PMID- 11204875 TI - Effects of exercise conditioning on vital age in hyperlipidemic women. AB - We attempted to determine the effectiveness of exercise prescription for women with hyperlipidemia (HL), because some HL women showed no significant improvement in serum lipid and lipoprotein profiles despite the continuation of exercise conditioning. We therefore tested the hypothesis that exercise can be clinically beneficial even when there are no alterations in total cholesterol (TC), low density lipoprotein cholesterol (LDLC), and/or triglycerides (TG). Twenty-three women with HL (aged 54.3 +/- 7.6 yr) participated in our outpatient-supervised exercise conditioning program for 90 minutes each session, twice a week for 1 year, and also did home-based exercise three days a week. Vital age (VA) is a useful index for assessing functional status, especially the risk of coronary heart disease (CHD) and is computed from 11 independent variables measured not only when a person is at rest but also during exercise. Although TC and LDLC did not change significantly after the exercise conditioning, TG decreased significantly (P < 0.05). Furthermore, when we computed the corrected VA (VAc) assuming no changes in TC, LDLC, and TG, VAc was found to decrease significantly from 64.0 +/- 9.9 yr to 58.4 +/- 9.0 yr (P < 0.05). In conclusion, these results indicate the effectiveness of exercise conditioning on risk of CHD in HL women, irrespective of alterations in the concentrations of serum lipid and lipoprotein. PMID- 11204876 TI - Reduced oxidative DNA damage by vegetable juice intake: a controlled trial. PMID- 11204877 TI - Host response and Histoplasma capsulatum/macrophage molecular interactions. AB - Histoplasma capsulatum is the etiological agent of histoplasmosis, a chronic respiratory infection that is generally asymptomatic in healthy individuals, but severe or fatal in patients who are immunosuppressed or otherwise debilitated. H. capsulatum is found as a mould in soil and becomes a pathogenic yeast in the mammalian host. The first line of defense that H. capsulatum faces during host invasion is the attack of polymorphonuclear neutrophils and resident macrophages. In animal models, once phagocytosed, H. capsulatum is not killed by fusion of the phago-lysosomes, instead it multiplies within non-activated macrophages and destroys them. Upon induction of cell-mediated immunity, cytokines activate macrophages and destroy the yeast cells. Some aspects of the fungus-macrophage interaction have been elucidated, and it is clear that some of the mechanisms by which H. capsulatum escapes the lethal effects of this very hostile environment, involve the regulation of specific genes. Recently, using the differential display reverse transcriptase polymerase chain reaction technique, a number of H. capsulatum genes that are induced after the yeasts are ingested by macrophages have been identified. However, the mechanisms that underlie the capacity of H. capsulatum to adapt to the new environmental conditions present in macrophages remain to be clarified. PMID- 11204878 TI - Immunoregulation by capsular components of Cryptococcus neoformans. AB - Cryptococcus neoformans is an encapsulated yeast that is pathogenic for humans. The capsule is a major virulence factor composed mainly of glucuronoxylomannan (GXM) and two minor constituents, galactoxylomannan, and mannoprotein (MP). A hallmark of disseminated cryptococcosis is the presence of high concentrations of GXM in body fluids of infected hosts. GXM provides a critical negative signal for T cell activation and neutrophil migration at the site of the inflammatory process. There is also strong evidence that MP promotes critical events associated with protective responses such as delayed type hypersensitivity and presumably a T helper type 1 response. The contrasting roles of GXM and MP in regulation of the immune response to C. neoformans offer a promising template for a successful approach to intervention, by scavenging GXM to attenuate its negative signals, while preserving the positive effects of MP. PMID- 11204879 TI - Local Th1/Th2 cytokine production during experimental vaginal candidiasis: potential importance of transforming growth factor-beta. AB - Host defense mechanisms against vaginal Candida albicans infections are poorly understood. Despite the protective role of T helper (Th)1-type cell-mediated immunity (CMI) against mucosal C. albicans infections, studies using an estrogen dependent murine model of vaginal candidiasis have shown a lack of effect of systemic Th1-type CMI against a vaginal C. albicans infection, and a lack of changes in local T cells during infection. In the present study, the local Thl- (interleukin [IL]-2, interferon [IFN]-gamma and IL-12) and Th2- (IL-4, IL-10 and transforming growth factor [TGF]-beta1) type cytokines were evaluated in vaginal tissue during an experimental C. albicans infection. Results showed constitutive expression of TGF-beta1 in vaginal tissue of naive mice that was two-fold higher than the levels of the other cytokines examined. These high levels of TGF-beta1 were further increased as a result of pseudoestrus and/or infection, and were corroborated at the messenger RNA level. Furthermore, the levels of TGF-beta in naive or infected mice were significantly higher in the vagina compared to other areas of the genital tract. Finally, TGF-beta1 predominated as well in the draining, but not non-draining, lymph nodes during infection. These results suggest that TGF-beta1, a potent immunoregulatory cytokine, may be important in the lack of demonstrable CMI at the vaginal mucosa against C. albicans. PMID- 11204880 TI - Mitochondrial DNA analysis of Sporothrix schenckii in South Africa and Australia. AB - Clinical isolates of Sporothrix schenckii were investigated for mitochondrial DNA (mtDNA) types using restriction fragment length polymorphism patterns with HaeIII. The 62isolates in South Africa comprised Types 3 (9.7%), 4 (1.6%), 11 (9.7%), 17 (77.4%) and 23 (1.6%) while the 23 Australian isolates comprised Types 3 (26.0%), 4 (56.5%), 7 (8.6%) and 21 (8.6%). In a phylogenetic tree based on the sequence divergence of mtDNA, the mtDNA types were clustered into two groups, A and B. The results suggested that isolates in South Africa mainly belong to Group A and isolates in Australia mainly belong to Group B. PMID- 11204881 TI - RFLP analysis reveals marked geographical isolation between strains of Paracoccidioides brasiliensis. AB - Restriction fragment length polymorphism (RFLP) was performed on 32 isolates of the pathogenic fungus Paracoccidioides brasiliensis from geographically separated regions of South America. The use of HinfI and HincII gave clear RFLP patterns, for which high discriminatory indices could be calculated. Computational analysis of the RFLP patterns for the 32 isolates suggested that at least five groups of strains existed, each of which was geographically distinct and corresponded closely with present country borders. These results underline the belief that P. brasiliensis infections are acquired from exogenous sources and that this fungus occupies specialist endemic niches within the natural environment. PMID- 11204882 TI - Lipid peroxidation by alveolar macrophages challenged with Cryptococcus neoformans, Candida albicans or Aspergillus fumigatus. AB - Increased formation of oxygen radicals has previously been shown for alveolar macrophages (AM) challenged with Cryptococcus neoformans cells opsonized with fresh serum or polyclonal immunoglobulin G. AM show similar responses to Candida albicans or Aspergillus fumigatus. Oxygen radicals are capable of damaging various macromolecules, including lipids. In the present study, lipid peroxidation (LPO) caused by AM incubated with the fungi was examined in the presence and absence of lung surfactant. The level of malonaldehyde was used as an indicator of LPO. AM damage was examined by electron microscopy (EM), by trypan blue exclusion and by counting the AM loss from culture dish to supernatant. Stimulation of AM by each fungus increased cellular LPO but did not affect AM viability. A slight surfactant LPO induced by AM alone was shown with significantly increased values after addition of each fungus. EM studies showed that dense lipid droplets, presumably consisting of oxidized lipids, were ingested in high amounts together with C. neoformans cells that had been opsonized in fresh serum, and in low amounts in combination with C. albicans. These processes were accompanied by increased numbers of AM in the supernatants. LPO and detachment of AM were counteracted by vitamin E. In the lungs, AM exposed to one of these fungal pathogens might promote peroxidation of surfactant lipids. PMID- 11204883 TI - Pneumocystis carinii pneumonia in a Yorkshire terrier dog. AB - A 14-month-old male Yorkshire terrier was presented to the Autonomous University of Barcelona Veterinary Teaching Hospital because of a history of chronic non productive cough and acute dyspnea. A follow-up radiograph revealed a diffuse, bilaterally interstitial-alveolar lung disease with presence of air bronchograms. The dog died 5 h after admission with severe dyspnea. Histological sections of the necropsy specimens revealed the presence of characteristic Pneumocystis carinii cysts within alveolar spaces. A diagnosis of P. carinii pneumonia (PCP) was made on the basis of these results. To our knowledge, PCP has not been described in a Yorkshire terrier dog. PMID- 11204884 TI - Road accidents in Slovenia involving a pedestrian, cyclist or motorcyclist and a car. AB - We analyse the group of road traffic accidents in Slovenia in which a car driver and a pedestrian, cyclist or motorcyclist are involved. At the beginning some basic data are presented from the available database on traffic accidents. The selected group is then analysed by use of the logistic regression method. Based on the obtained results, some guidelines for transport policy action--aimed at decreasing the number of accidents with severe injury or fatality--are identified. PMID- 11204885 TI - An evaluation of a suburban railway pedestrian crossing safety programme. AB - This study evaluated a programme of educational and environmental (access prevention) interventions designed to reduce the incidence of illegal and unsafe crossing of the rail corridor at a suburban station in Auckland, New Zealand. Immediately after the programme of interventions, the proportion of those crossing the rail corridor by walking across the tracks directly rather than using the nearby overbridge had decreased substantially. Three months later, the decrease was even greater. However, the educational and environmental interventions were introduced simultaneously so that the effects of each could not be separated; nor could other unmeasured factors be ruled out. Anonymous surveys administered immediately before and 3 months after the interventions indicated that while awareness of the illegality of walking across the tracks had increased slightly, perception of risk had not changed. This suggests that the educational interventions may have had less effect than the access prevention measures. PMID- 11204886 TI - Age and gender patterns in motor vehicle crash injuries: importance of type of crash and occupant role. AB - To evaluate the interaction of gender, age, type of crash, and occupant role in motor vehicle crash injuries leading to hospitalization, we analyzed 1997 Wisconsin hospital discharge data for patients with primary E-code diagnoses of motor vehicle injuries. The overall ratio of males to females (M/F ratio) hospitalized for motor vehicle crash injuries was 1.33 (95% confidence interval (CI): 1.26-1.41). The M/F ratio varied by type of crash and differed for passengers and drivers. For injuries sustained in collisions between vehicles, the M/F ratio was 0.96 (95% CI: 0.87-1.05); in loss of control accidents the M/F ratio was 1.95 (95% CI: 1.76-2.17). Within each type of crash, the M/F ratio for drivers was similar to that for the entire type; the M/F ratio for passengers was about half of the type total. Expressed as rates of hospitalization per 100,000 people in the general population, hospitalizations of drivers in collisions with another motor vehicle increased steeply in males, but not in females, beginning at about age 70. For drivers in loss of control crashes, male rates exceeded female rates in all age groups, with peaks in the groups 15-24 and 85-89. For passengers, injury rates from collisions with other motor vehicles were greater for females, especially in the elderly, and injury rates from loss of control crashes were similar for both genders, with peaks at 15-24 and 85-94. The higher fatality of men in loss of control motor vehicle crashes, compared to women, suggests an important area for further investigation. PMID- 11204887 TI - Pedestrian fatalities and alcohol. AB - Since the share of alcohol-positive victims has been reported not to show the same reduction in pedestrian fatalities as in other 'road users', this study analysed pedestrian fatalities with special emphasis on the presence of alcohol. Autopsied pedestrian fatalities (286 victims) in northern Sweden from 1977 to 1995 were investigated, using autopsy and police reports. Blood alcohol was detected in 19% of the fatalities, with a median concentration of 1.6 g/l. The proportion of test-positive victims did not change significantly during the period of study. Males more often tested positive for alcohol than females (24 vs. 11%). Further, the test-positive victims had a lower mean age (49 vs. 59 years) and the proportion of test-positive victims was higher during weekends and nights. Pedestrian fatalities testing positive for alcohol differ from those testing negative in several respects. The public should be enlightened of the fact that drinking is a risk not only among users of motor vehicles, but also among pedestrians. Separation of pedestrians from motor vehicles by, e.g. fences, is of greatest importance. PMID- 11204888 TI - Variations of the level of vigilance and of behavioural activities during simulated automobile driving. AB - During a monotonous activity, certain behaviours occur that are not necessary to the performance of the task. These are subsidiary or collateral activities. Our purpose was to find out if the number of these behaviours tends to increase during a monotonous and prolonged activity. A study was carried out with 17 subjects performing a 2-h car drive on the Vigilance Analysis Driving Simulator. An analysis of the drivers' behaviour and of their state of vigilance allowed us to confirm the existence of a relation between the occurrence of these behaviours and the variations of the level of arousal. In addition, we determined for all produced behaviours, those that preceded, those that coincided with, and those that followed low vigilance phenomena. These results were interpreted in terms of behavioural signs, precursory of low vigilance, indicative of low vigilance, or reactivating the driver. PMID- 11204889 TI - Fatal traffic accidents among trailer truck drivers and accident causes as viewed by other truck drivers. AB - Causality factors, the responsibility of the driver and driver fatigue-related factors were studied in fatal two-vehicle accidents where a trailer truck driver was involved during the period of 1991-1997 (n = 337). In addition, 251 long-haul truck drivers were surveyed in order to study their views regarding contributing factors in accidents involving trucks and the development of possible countermeasure against driver fatigue. Trailer truck drivers were principally responsible for 16% of all the accidents. Younger driver age and driving during evening hours were significant predictors of being principally responsible. In addition, the probability of being principally responsible for the accident increased by a factor of over three if the driver had a chronic illness. Prolonged driving preceding the accident, accident history or traffic offence history did not have a significant effect. Only 2% of the drivers were estimated to have fallen asleep while driving just prior to the accident, and altogether 4% of the drivers had been tired prior to the accident. Of the drivers 13% had however, been driving over 10 h preceding the accident (which has been criminally punishably in Finland since 1995 under the EC regulation) but no individual factors had a significant effect in predicting prolonged driving. The surveyed views regarding causes of truck accidents correspond well with the accident analysis. Accidents were viewed as being most often caused by other road users and driver fatigue was viewed to be no more than the fifth (out of eight) common cause of accidents. The probability of viewing fatigue as a more common cause increased significantly if the driver had experienced fatigue-related problems while driving. However, nearly half of the surveyed truck drivers expressed a negative view towards developing a technological countermeasure against driver fatigue. The negative view was not related to personal experiences of fatigue related problems while driving. PMID- 11204890 TI - Multiple state hazard models and workers' compensation claims: an examination of workers compensation data from Ontario. AB - The recurrent nature of some workplace injuries has led some researchers to conclude that the first absence from work does not provide an accurate picture of an individual's claim, or employment history, after a workplace injury. In this paper I estimate a multiple state hazard which estimates the transitions between spells where the individual receives workers' compensation benefits and spells where the individual does not receive any workers' compensation benefits. I apply this model to a sample of claims from Ontario's Workplace Safety and Insurance Board. PMID- 11204891 TI - Factors associated with parental safe road behaviour as a pedestrian with young children in metropolitan New South Wales, Australia. AB - A cross-sectional population-based randomised telephone survey of parents with children aged between 5 and 12 years was conducted to investigate factors associated with safe road behaviour of parents as pedestrians with their young children in Sydney metropolitan and near by cities in New South Wales, Australia. Parental perception of the road environment as hazardous associated significantly with their safe road behaviour as pedestrian while with their children. This held true even after adjusting for the non-English speaking background and the age of the child. Knowledge of road rules, on the other hand, was not associated with parental safe road behaviour. The results of this study suggested that parental safe road behaviour require much attention in future research and in programme development. The perception of the road environment is a very important factor in motivating safe road behaviour. This should be taken into consideration in designing road safety campaigns. PMID- 11204892 TI - A linkage study of Western Australian drink driving arrests and road crash records. AB - Records of drivers in all reported road crashes occurring in Western Australia between 1987 and 1995 were linked with records of all drink driving arrests in the same period. About 7% of all drink driving arrests occurred because of a road crash. Differences were observed between these drink-driving crashes and other types of road crashes. Drink driving crashes tended to be more severe than those not involving alcohol. Serious crashes (involving fatalities or hospitalisations) accounted for 20% of alcohol-related crashes, but only 6% of all crashes reported over the study period. From another perspective, crash-related drink-driving arrests were more likely than routine enforcement arrests to involve younger (18 35 years) and older (65 years and over) drink drivers. Routine enforcement arrests, on the other hand, were likely to involve a greater proportion of Aboriginal drivers. PMID- 11204893 TI - Novice drink drivers, recidivism and crash involvement. AB - A group of drink drivers with no prior arrest for drink driving was selected from drink driving arrest records originating in Western Australia between 1987 and 1995. These drink-driving records were linked to road crash records for the same period. The analysis of these combined records focussed on the sequence of driving events (i.e., arrests, crashes and arrests resulting from crashes) and the present article explores the relationship in time between known drink driving incidents and crash involvement. Using multi-variate survival analysis, it was found that if a driver's first drink driving offence resulted from a road crash, especially if this occurred at a younger age, he/she was significantly more likely to drink, drive and crash again. PMID- 11204894 TI - Relationship of parent driving records to the driving records of their children. AB - Many studies have shown that young driver crash rates can be influenced by such factors as lifestyle characteristics and licensing systems. However, the influence of parents on their teenage children's crash and violation rates has not received much attention. The present study used data from the North Carolina driver history file to match the crash and violation records of young drivers between the ages of 18 and 21 with those of their parents. Results indicate that children's driving records in the first few years of licensure are related to the driving records of their parents. Children whose parents had three or more crashes on their record were 22% more likely to have had at least one crash compared with children whose parents had no crashes. Likewise, children whose parents had three or more violations were 38% more likely to have had a violation compared with children whose parents had none. Logistic regression models showed that these relationships held when controlling for household type and child gender. PMID- 11204895 TI - Restraint use patterns for older child passengers in Michigan. AB - The purpose of the present study was to conduct the first statewide direct observation survey of restraint use designed specifically for older child passengers (4-15 years of age). We also sought to determine the factors that were related to belt use by older child passengers in Michigan so that effective programs could be developed to promote use of restraint devices in this age group. The study found that older child restraint use was about 58% statewide. Restraint use was highest in regions where overall belt use was higher, when the driver was using a safety belt, in sport utility vehicles and vans/minivans, and in the front-right seating position. No difference in restraint use was found for the day of week, the sex of the child, or the type of site where data was collected. The study provides the largest scale analysis to date on older child occupant restraint use patterns. The data provide some much needed empirical data on the restraint use patterns of older child passengers for development of theory to better understand and predict lack of restraint use in this age group. PMID- 11204896 TI - Are aggressive people aggressive drivers? A study of the relationship between self-reported general aggressiveness, driver anger and aggressive driving. AB - In this study the relationships among self-reported general aggressiveness, impulsiveness, driver anger, and aggressive responses to anger-provoking situations on the road were studied. The British version of a driver anger scale (UK DAS), aggression questionnaire (AQ), and an impulsiveness questionnaire (I7) together with background questions (gender, age, annual mileage) were administered to a sample of 270 British drivers. Variation in strength of correlations between anger and aggressive reactions in the 21 UK DAS items showed that the relationship between driver anger and aggression depends in part on the characteristics of the situation. In addition, three path models for describing the relationships among the measures were constructed separately for women and men. The models suggested that the effects of verbal aggressiveness on self reported driver aggression were mediated by driver anger whereas physical aggressiveness was directly related to aggressive behaviour. Age was negatively related to both driver anger and aggression among men whereas annual mileage was negatively related to aggression among women. The models constructed indicate that aggressive driver behaviour is a complex phenomenon with a range of psychological causes. PMID- 11204897 TI - Effects of low-dose alcohol exposure on simulated merchant ship piloting by maritime cadets. AB - The US Department of Transportation (DOT) regulates on-the-job alcohol use by operators of certain categories of commercial transport. For aircraft, trains, and commercial vessels, operators are subject to sanctions for having > or = 0.04 g% blood alcohol concentration (BAC). This study examines the effects of alcohol (between 0.04 and 0.05 g% BAC) on simulated merchant ship handling. A two-group randomized factorial design was used to compare beverage alcohol to placebo while controlling for baseline performance on a previous day. The study was conducted in the Maritime Simulation Center at Maine Maritime Academy, Castine, ME. Participants were 38 volunteer deck officer cadets in their junior or senior year, at least 21 years of age, with previous experience on a bridge simulator. Following a baseline trial on Day 1, on Day 2 participants were randomized to receive alcohol (0.6 g/kg for males and 0.5 g/kg for females) or placebo. After allowing time for absorption, participants completed a bridge simulator task. For baseline and performance trials, participants were randomized to one of four bridge simulator scenarios, each representing passage of a fully loaded container vessel through a channel with commercial traffic. The aggregate scenario score given by blinded maritime educators measured performance. A main effect for alcohol was found indicating that performance was significantly impaired by this low dose of alcohol relative to performance in the placebo condition. These findings are consistent with current federal regulations that limit low-dose alcohol exposure for the operators of commercial transport vehicles. Further research is required to determine effects at lower BACs. PMID- 11204898 TI - Accident prototypical scenarios, a tool for road safety research and diagnostic studies. AB - The concept of prototypical accident scenario has been used since the late 1980s in French road safety research. A prototypical scenario can be defined as a prototype of the accident process corresponding to a series of accidents which are similar in terms of the chain of facts and causal relationships found throughout the various accident stages. This concept provides a means of combining and generalising the knowledge obtained from accident case studies, based on in-depth investigation methods or on detailed analyses of police reports. Applications of this concept are developed in both the field of traffic accident research and safety studies (diagnoses) in preparation for engineering measures or local safety policies. This paper presents the prototypical scenario concept, its theoretical background, and the way it is used for safety research and studies. PMID- 11204899 TI - The relative effectiveness of a hidden versus a visible speed camera programme. AB - Overtly operated mobile speed cameras have been used in New Zealand since late 1993. Their operation has been confined to specific sites (called 'speed camera areas') which are mainly road sections with a record of speed-related crashes. A trial of hidden speed cameras began in mid-1997 in 100 km/h speed limit areas in one of New Zealand's four Police regions. This trial was still in progress at the time of writing and the current paper reports the results of an evaluation of the first year of the trial. During that period, the hidden cameras and related publicity were found (compared with the generally highly visible speed camera enforcement in the rest of New Zealand) to be associated with net falls in speeds, crashes and casualties both in speed camera areas and on 100 km/h speed limit roads generally. There were initial changes in public attitudes in response to the programme that later largely reverted to pre-trial levels. Compared with the localised effect of visible cameras on speeds and crashes mainly in speed camera areas, the hidden cameras had a more general effect on all roads. As further crash, speed and attitude data become available, the longer-term effects of the hidden camera programme will be evaluated. PMID- 11204900 TI - Passengers' injuries reflected carriage interior at the railway accident in Mundelstrup, Denmark. AB - On 1st March 1994, a passenger train with a speed of 85 km/h ran into the rear end of a stopped passenger train north of Aarhus, Denmark. No fatalities occurred. Questionnaires were sent to passengers and crew and 113 of 128 (88%) answered. In the stopped train 32% (9/28) of the sitting passengers compared with 12% (9/76) in the moving train had symptons corresponding to a whiplash lesion. Only the chairs in the moving train had head rests which might explain the observed difference. In the rest section of the moving train with all seats facing the same direction 81% (13/16) of the sitting passengers had face injuries compared to 13% (8/60) in the rest of the train. The higher incidence in the rest section was caused by folding tables at the back of the seats. Serious thoraco abdominal injuries were only seen in one patient despite the fact that 37 passengers were thrown againsts tables between the seats in the second class section of the moving train. The tables were fragile and usually gave way. In conclusion, carriage interior has a major influence on personal injuries at railway accidents. PMID- 11204901 TI - The secrets of involvement, Part II. PMID- 11204902 TI - A handy interviewing tool. PMID- 11204903 TI - State-of-the-art exhaust hood. PMID- 11204904 TI - Taking out violence. AB - An analysis of how consequences impact your company from inside or outside will enable you to prevent the situations that can build up until they explode into violence. Specific skill enhancement on the use of feedback and consequences will broaden the base of involvement and foster early intervention opportunities before things get out of control. Understanding how consequences influence behavior also can improve self-management efforts. When these strategies are coupled with security hardware and appropriate policies, we can once again help our managers and employees work without fear of violence. PMID- 11204905 TI - Solving the language barrier. PMID- 11204906 TI - Compliance and procurement in the e-age. PMID- 11204907 TI - Slips & falls on the manufacturing floor. PMID- 11204908 TI - From conversation to commitment. PMID- 11204909 TI - Automation paves the way to improved gas monitoring. PMID- 11204910 TI - The basics for smaller businesses. PMID- 11204911 TI - Making sense of hand protection. PMID- 11204912 TI - Building employee enthusiasm. PMID- 11204913 TI - Ryder gets it done. PMID- 11204914 TI - Reducing the severity of MSDs in manufacturing. PMID- 11204915 TI - It's all in the adjustments. PMID- 11204916 TI - Revitalizing your ergonomics program. PMID- 11204917 TI - Jeffress's big bang. PMID- 11204918 TI - [Epidemiology of nosocomial infections in pediatrics]. AB - The overall incidence of nosocomial infections (NI) in pediatrics ranges between 2.3% to 12.6%. They have great variations according to age (7-12% under 1 year of age vs 1.5-4% after ten years of age), and the nature of the unit (3-26% in intensive care units vs 1-4% in general pediatrics). The main sites of infection are in children gastrointestinal infections (10-35% of NI) and bacteremia (10-23% of NI) whereas in adults urinary tract infections (31.7 to 35%) and respiratory infections (19 to 25%) are the most frequent. Viruses represent 22-27% of the isolated pathogens, and Gram positive cocci 31-50% (half of them are coagulase negative staphylococci). The most frequent Gram negative bacilli are Pseudomonas aeruginosa (9-15%), E. coli (6-16%) and Klebsiella pneumoniae (3-5%). Candida represent 3% of isolated pathogens in NI. The proportion of methicilline resistant Staphylococcus aureus is lower in children than in adults. The prevalence of methicillin resistance of CNS is however close to that observed in adults, as is the multiresistance of Gram negative bacilli (Klebsiella). Candida infections seem an emerging problem in paediatrics. These results underline the necessity to limit the antimicrobial therapy in children as in adults. PMID- 11204919 TI - [Epidemiology of viral nosocomial infections in pediatrics]. AB - Nosocomial viral infections account for at least 5% of the total of NI and reach 23% in pediatric wards. The nosocomial infection (NI) incidence rate varies from 0.59 to 0.72 per 100 patients in pediatric wards. Many viruses have been associated with NI in pediatric wards. Rotavirus and respiratory syncytial virus (RSV) are the most frequent. Other viruses frequently identified are: calicivirus, adenovirus, astrovirus, influenza et para-influenza, rhinovirus and coronavirus. Asymptomatic infections occur frequently. The period of communicability varies and depends on the virus. It often begins before the clinical signs appear and ends after the healing. Viral shedding may be intermittent. Children and hospital environment and less frequently hospital staff are the main source for the virus. Poor handwashing results in direct spread to patient or self-inoculation even for respiratory viruses like RSV and rhinovirus. The main risk factors for NI are prolonged hospital stay, past history of prematurity and low age. Immunocompromised patients constitute a special high-risk group. Understaffing is also a risk factor. Minimal infective doses depend on the route of inoculation and the kind of virus. Low doses are for example sufficient for rotavirus, adenovirus and calicivirus. Viral inactivation is all the more easy when there is an envelope. Handwashing and appropriate isolation (technical and geographical) are the mainstay of prevention of viral NI. Vaccines are promising, especially for rotavirus. PMID- 11204920 TI - [Nosocomial infections in immunocompromised children]. AB - Immunocompromised children are at high risk for developing nosocomial infections which may cause significant morbidity and mortality in this population. In paediatric oncology, reported prevalence of nosocomial infections varies from 10 to 20%. Major predisposing factors are neutropenia, central venous catheter, corticosteroid therapy and hospital construction or renovation for invasive aspergillosis. The management of patients with febrile neutropenia should take into account the previous history of infection and the microbiologic environment of each department. Nowadays, Gram positives infections are predominant, but fungal infections remain a major threat. In organ transplant recipients, wound infections are the main early problems, followed by viral infections often due to the donor CMV seropositivity. In HIV-infected children, nosocomial infections are difficult to define, and can implicate unusual pathogens. In general, adapted preventive infection control strategy warrants prospective studies. PMID- 11204921 TI - [Nosocomial infections in mother and child: specific risks in the labour ward]. AB - Nosocomial infection is a frequent and potentially lethal complication in obstetrics. The incidence of this complication may be underscored and an accurate surveillance system must be used in each obstetrics unit for infection control. This surveillance system should also identify the patients at risk for infection in order to improve prevention efforts. beta-lactam-sensitive streptococcus is often involved in obstetrical infections and a short antibio-prophylaxis is indicated in most obstetrical procedures. Disinfection strategy, guidelines for clinical practice and control charts should be established in each obstetrics unit to prevent nosocomial infections. PMID- 11204922 TI - [Efficacity of antiseptic products]. AB - Chemical antiseptics are used in specified conditions. This work studied the actual standards to evaluate the activity of antiseptics. Afterward, the main indications of antiseptics are summarized. PMID- 11204923 TI - [Nosocomial infections in pediatrics. Problems and perspectives]. AB - High incidence of nosocomial infections in children is largely explained by immunodeficiency, particularly in newborns. Central venous catheter is the main risk factor and coagulase negative staphylococcus the main pathogen in cause. Large variations of nosocomial infection incidences are observed by Nososcomial Infection Surveillance Networks and depend on the pediatric speciality. The highest rate is observed in neonatal intensive care, where incidence density of catheter-related sepsis varies from four to 23 infections for 1000 catheter-days. Local surveillance in each ward, risk factors and knowledge of bacterial epidemiology allow the development of rational preventive and therapeutic protocols. However, prophylactic use of vancomycin is dangerous and immunoglobulins are inefficient. PMID- 11204924 TI - [Recent developments of spoligotyping as applied to the study of epidemiology, biodiversity and molecular phylogeny of the Mycobacterium tuberculosis complex]. AB - Spoligotyping (for 'spacer-oligonucleotide-typing'), a rapid method for genotyping of Mycobacterium tuberculosis complex using the principle of reverse hybridization, is based on the structure of the direct repeat (DR) locus. The DR locus is made up of a variable number of 36 bp DR repeats that are separated by unique inter-DR sequences of 35 to 41 bp. Fast and highly discriminatory, spoligotyping is an useful alternative to the IS6110-RFLP reference method for molecular typing of M. tuberculosis, in particular for isolates possessing five or few copies of IS6110. In this paper, we review the state of the art of spoligotyping through its main current applications. After a brief introduction to the principle of the technique and its description, we successively review recently published results concerning the molecular epidemiology of tuberculosis in humans and cattle, and discuss the main genotyping strategies currently in use to fingerprint the M. tuberculosis complex organisms. We also describe the recent applications of spoligotyping to study ancient DNA and report on recent developments of this technique to study the biodiversity of the M. tuberculosis complex, its contribution towards improved taxonomy and phylogenetics of the M. tuberculosis complex. Last but not least, potential applications of spoligotyping to study DNA recombination mechanisms are also discussed. PMID- 11204925 TI - [Comparative antibacterial activity of cefotaxime, ceftazidime and cefepime with regard to different strains of Enterobacter aerogenes selected for their resistance to third generation cephalosporins]. AB - After being confronted with the isolation in our laboratory of numerous antibiotic-multiresistant Enterobacter aerogenes strains, we studied the in vitro antimicrobial activity of cefotaxime, ceftazidime, and cefepime alone or in association with sulbactam. For that, we selected 67 isolates according to their low level of susceptibility to cefotaxime. First, we deduced from a synergy test in presence of clavulanic acid and cloxacillin the production of an extended spectrum beta-lactamase (ESBL) and/or an overproduction of a chromosomal cephalosporinase. Three groups of strains were thus defined: one group of ESBL strains, another group of overproducing strains of chromosomal cephalosporinase, and a last group that produced the two types of enzymes. Minimal inhibitory concentrations (MICs) of each cephalosporin alone or in presence of 8 mg/L of sulbactam, gentamicin or amikacin were measured. Our results demonstrated the best activity of cefepime: MICs were low with a value inferior to 4 mg/L independently of the type of beta-lactamase. They were lower than 0.5 mg/L in presence of sulbactam against ESBL-producing strains. The cephalosporins could be used in association with aminoglycosides according to their susceptibility. PMID- 11204926 TI - [Veterinary use of antibiotics and resistance in man: what relation?]. AB - Early in the 1950's antibiotic therapy was introduced in humans, as well as in animals. In 1997 48% of the total European antibiotic sales were intended to veterinary use. However, there are significant differences between antibiotic classes regarding either administered quantities or intent for use, e.g. growth factor or therapeutic use. Furthermore, food chain or direct contact may be responsible for antimicrobial resistance through animal-to-human transmission. Although various preventive measures were implemented during the past years, evidence of public health risks has been demonstrated. This should lead to better use of antibiotic therapy not only in animal husbandry but also in medical practice. PMID- 11204927 TI - [Organic pig farming: what about parasitic infections?]. AB - The parasitological problems that may arise in organic pig farming are discussed. The rearing of pigs outdoors increases substantially the chances that several parasite species will complete their life cycle. Moreover, zoonoses may play an important role. Parasite species that may cause problems are discussed, as are control measures, when possible. PMID- 11204928 TI - [Protocol for post partum cows]. PMID- 11204929 TI - [BSE testing in the Netherlands]. PMID- 11204930 TI - [Artificial insemination]. PMID- 11204931 TI - Evidence based medicine, RCTs and their natural enemies: the clinical pharmacologist's role. PMID- 11204932 TI - Drug-related visits to the medical emergency department: a prospective study from India. AB - OBJECTIVE: To analyze the contribution of adverse drug events (ADEs) to the overall number of visits to the medical emergency and to determine the proportion of events leading to hospital admissions. PATIENTS AND METHODS: All visits to the medical emergency were recorded in a prospective, non-interventional design study over a period of 8 months. The ADEs were divided into 5 categories: adverse drug reactions (ADRs), drug interactions, patient non-compliance, physician non compliance, and drug overdose. The cases were then followed-up to assess the prorportion of ADEs lead to hospitaliztion. RESULTS: A total of 4764 patients were included in the study. 5.9% of all visits were considered to be drug related. The highest percentage of ADEs was observed in the age group less than 20 and more than 80 years. ADRs accounted for 45% of all ADEs, followed by patient non-compliance (28%). Patient and physician non-compliance were the main causes of drug-related hospital admissions. 52% of all ADE-related visits and 55% of ADE-related admissions were considered to be preventable. Non-steroidal antiinflammatory agents, oral hypoglycemics and antitubercular drugs were responsible for 37% of all ADRs. Non-compliance was mainly seen in hypertensives, asthmatics and epileptics. CONCLUSION: ADEs account for a sizable proportion of all visits to a medical emergency unit and some are serious enough to require hospitaliztion. A large number of ADE-related visits and admissions are preventable which highlights the importance of public education on the proper use of drugs, and also the need for regulation of the practice of unregistered medical practitioners in developing countries. PMID- 11204933 TI - Effect of calcium antagonists on stress-induced rise in blood pressure and heart rate: a double-blind, placebo-controlled study. AB - OBJECTIVE: The current study was designed to evaluate the effect of treatment with calcium antagonists on stress-induced increases in blood pressure and heart rate. SUBIECTS, MATERIAL AND METHODS: Two models of stress were chosen, cold stress and isometric handgrip exercise. Six healthy volunteers were randomized to receive amlodipine (5 mg), lacidipine (4 mg) for a two-day period in a double blind, crossover design. Thirty hypertensive patients received the same treatment for a period of one week in a double-blind, parallel design. The effects of stress on blood pressure and heart rate were taken at baseline and after drug treatment. RESULTS: Cold stress and handgrip exercise significantly increased the systolic and diastolic blood pressure as well as the heart rate. In normotensive volunteers, the resting heart rate and blood pressure were not altered by the drugs. The increase in systolic and diastolic blood pressure produced by cold stress and isometric exercise were unchanged by amlodipine and lacidipine. In hypertensive patients, both drugs reduced the resting blood pressure (p < 0.05). As in normotensive individuals, the pressor response to stress was not altered by the drugs. CONCLUSION: Cold stress and handgrip exercise produced a significant rise in blood pressure and heart rate in normotensive volunteers and patients with hypertension. Cardiovascular reactivity to cold stress and handgrip exercise is not altered by the administration ofamlodipine and lacidipine. PMID- 11204934 TI - Caffeine metabolism in a group of 67 patients with primary biliary cirrhosis. AB - OBJECTIVE: To evaluate the polygenic regulated caffeine metabolism in a group of 67 patients with a documented primary biliary cirrhosis (PBC) classified according to the histologic stage proposed by Scheuer. METHODS: Over a 14-year period, drug liver metabolism, using caffeine as a probe drug, has been systematically carried out in addition to the usual clinical, histological and biochemical investigations performed in patients with PBC. The "Caffeine test" consisted of a 200 mg caffeine oral intake. Urines were collected over 24 hours: caffeine (137X), 1-7-dimethylxanthine (17X), 1-3-dimethylxanthine (13X), 1-3 dimethylurate (13U), 3-7-dimethylxanthine (37X), 1-7-dimethylurate (17U), 1 methylxanthine (1X), 1-methylurate (1U), 7-methylxanthine (7X), 3-methylxanthine (3X), and 5-acetylamino-6-formylamino-3-methyluracyl (AFMU) were analyzed by high performance liquid chromatography (HPLC). Total and individual metabolite urinary elimination rates were expressed in micromol/24 hours. Enzyme activities were evaluated from the following urinary metabolite ratios: (AFMU+1U+1X)/17U for CYP1A2, 17U/17X for CYP2A6, AFMU/(AFMU+U+ 1X) for NAT-2, 1U/1X for XO. RESULTS: Compared to healthy subjects, patients with PBC presented a reduced metabolism of caffeine due to a decreased CYP1A2 activity, all the more important since the patients had an advanced histological stage. This picture was nearly identical to the observed picture in chronic liver diseases from various origins. PBC affected the various metabolic pathways of caffeine in a differential manner. CYP1A2 activity was decreased but XO and mainly CYP2A6 activities were increased as shown by the raised urinary ratio 17U/total metabolite elimination. In contrast to the described loss of bimodality of the NAT-2 index distribution in patients with alcoholic cirrhosis, we found a clear-cut, bimodal distribution in patients with PBC, without a high incidence of slow acetylator status. CONCLUSION: Metabolism of caffeine is strongly and differentially disturbed in patients with PBC and apparently not exactly in the same way as that in alcoholic cirrhosis which is more often taken as an index of chronic liver disease. This suggests the need for caution with medicines whose metabolism is under polygenic regulation. Because of the relationships between caffeine metabolism modifications and histological stages, the caffeine test might be used along with the usual tests to safely follow-up the evolution of the disease. PMID- 11204935 TI - Piroxicam concentrations in plasma and synovial fluid after a single dose of piroxicam-beta-cyclodextrin. AB - AIMS: The efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in rheumatic diseases depends on their concentrations within the joint. We determined piroxicam concentrations in plasma and synovial fluid (SF) after a single oral dose of 20 mg in the form of one tablet of piroxicam-beta-cyclodextrin. METHODS: 45 patients, aged 21 to 84 years, presenting with an effusion of the knee, related to degenerative or inflammatory joint disease, were included in this study after having given their written consent. One blood and one SF sample were drawn concomitantly in each patient from 0.5 to 48 h after NSAID administration. Piroxicam assays were performed by high performance liquid chromatography. Pharmacokinetic parameters were obtained from the mean plasma and synovial concentrations measured at various sampling times. RESULTS: The peak concentration was higher in plasma (2.51+/-0.25 microg/ml) than in SF (1.31+/ 0.76 microg/ml), but the elimination half-life was much longer in SF (90.7 h) than in plasma (32.5 h). The SF/plasma area under the concentration-time curve ratio (evaluating the quantity of NSAID transferred from the blood to the joint) was equal to 0.39. CONCLUSIONS: Piroxicam contained in piroxicam-beta cyclodextrin diffused well into the SF where its pharmacokinetic profile corresponded to that of a long half-life NSAID. PMID- 11204936 TI - Estimated coefficient of variation values for sample size planning in bioequivalence studies. AB - OBJECTIVE: The aim of the present communication is to provide information regarding the intrasubject coefficent of variation obtained from 30 bioequivalence studies covering 16 drugs which can be used for estimation of sample size. Additionally, an attempt was also made to estimate the test power of each of the studies conducted. METHODS: The intrasubject coefficient of variation was estimated from the residual mean square error obtained from analysis of variance of the parameters AUC0-infinity, Cmax and Cmax/AUC0-infinity after logarithmic transformation. The test power in the analyses of the above parameters was subsequently estimated using nomograms provided by Diletti et al. [1991]. RESULTS AND CONCLUSION: Thirty products covering 16 drugs were studied in which 22 were immediate-release (including one dispersible tablet) and 8 were sustained-release formulations. The intrasubject coefficient of variation for the parameter AUC0-infinity was smaller than Cmax, and hence considerably more studies were able to attain a power of greater than 80% using 12 volunteers for the AUC0-infinity, compared to the Cmax. However, the variability in the Cmax could be reduced by using the parameter Cmax/ AUC0-infinity, and thus, provide a more realistic estimation of sample size, since the latter reflects only the rate of absorption and not both the rate and extent as in the case of Cmax [Endrenyi et al. 1991]. PMID- 11204937 TI - Antiviral drugs in chronic hepatitis B: review and meta-analysis. AB - Many researchers have attempted to identify the drugs capable of acting on the viral replication cycle and maintaining clinical remission in chronic hepatitis B. We evaluated the efficacy of antiviral drugs in chronic hepatitis B, by examination of 20 controlled and non-controlled trials conducted between 1985 and 1996. In chronic hepatitis B, adenine arabinoside and its monophosphate did not achieve satisfactory results, even though combination therapy with cortisone seemed to achieve very good results (remission rates ranging from 45% to 66% in patients treated). Lamivudine did not seem to furnish lasting effects in chronic hepatitis B, because many patients relapse after suspension of the treatment due to the appearance of HBV variants resistant to the drug. Contrasting results were observed with famciclovir. Treatment of chronic hepatitis B, with this drug seemed capable of reducing HBV-DNA serum levels by a mean of 50% compared to pretreatment values, with normal alanine aminotransferase levels in about 30% of treated patients. Ganciclovir treatment of chronic hepatitis B seemed to furnish good, but transient, results. Even if no antiviral drug represented a valid alternative to interferon, antivirals may become the drugs of choice in chronic hepatitis B, because they are aimed at the etiology of disease. PMID- 11204938 TI - Bioequivalence and relative bioavailability of three estradiol and norethisterone acetate-containing hormone replacement therapy tablets. AB - OBJECTIVE: The primary objective was to demonstrate bioequivalence between the estrogen components ofActivelle (1 mg estradiol (E2) + 0.5 mg norethisterone acetate (NETA)) and the combined phase of Novofem (1 mg E2 + 1 mg NETA) and between the NETA components of the combined phase of Novofem (1 mg E2 + 1 mg NETA) and Trisequens (2 mg E2 + 1 mg NETA). SUBJECTS, MATERIALS AND METHODS: The study design was double-blind, randomized, three-way, balanced six-sequence cross over. The washout period was 14 days between treatments. Single doses of the above-described tablets were administered in the morning following an overnight fast to 24 healthy postmenopausal or bilaterally oophorectomized women. Plasma concentration profiles of E2, estrone (E1; pharmacologically active metabolite of E2) and norethindrone (NET: NET was determined since NETA is very rapidly metabolized to NET) were measured over 72 h, and 36 h, respectively. For the two former substances a baseline correction was performed by subtracting the mean of two predose measurements from the concentrations measured after dosing. RESULTS: One subject dropped out of the study, completing only one treatment sequence; therefore, the results are based on 23 subjects. The baseline-corrected E2 and E1 AUC0-t (Novofem)/AUC0-t (Activelle) ratios were 105% and 100%, respectively; and the Cmax ratios 100% and 105%, respectively. Identical median tmax was observed for E2 (6 h) and for E1 (5 h). The NET AUC0-t (Novofem)/AUC0-t (Trisequens) ratio was 95%, and the corresponding Cmax ratio 98%. The median tmax for Novofem was 0.75 h and for Trisequens 1.0 h. CONCLUSION: Bioequivalence was demonstrated for E2, E1 and NET in accordance with the study objectives. PMID- 11204939 TI - Use of charge-transfer complex formation for the spectrophotometric determination of nortriptyline. AB - Three simple and selective methods are proposed for the determination of nortriptyline hydrochloride in bulk form and in tablets. The first two methods are based on the formation of charge-transfer complexes between the drug base as a n-donor and quinhydrone or p-chloranil as pi-acceptor. The products exhibit absorption maxima at 497 and 560 nm in acetonitrile for quinhydrone and p chloranil, respectively. The third method is based on the interaction of N alkylvinylamine formed from the condensation of the free secondary amine group and acetaldehyde with p-chloranil to give a vinylamino substituted quinone. The coloured product exhibits an absorption maximum at 650 nm in dioxane. All variables were studied to optimize reaction conditions. Beer's law was obeyed and the relative standard deviations were found to be less than 1.5%. The methods have been applied to the analysis of nortriptyline hydrochloride in the bulk drug and in tablets. PMID- 11204940 TI - Synthesis and calcium antagonistic activity of 2,6,6-trimethyl-3 carbomethoxy(ethoxy)-4-aryl-1,4,5,6,7,8-hexahydroquinoline derivatives. AB - Twelve new 2,6,6-trimethyl-3-carbomethoxy(ethoxy)-4-aryl-1,4.5,6.7,8 hexahydroquinoline derivatives have been prepared. Their structures were confirmed by IR, 1H NMR, mass and elemental analysis. The calcium antagonistic activity of these compounds was tested in rat aortic rings precontracted with 30 mM K+. The compounds IVa, IVc, IVe, IVf, IVh-l induced concentration dependent relaxation response in precontracted aortic rings. The concentrations that cause 50% relaxation of K+-contraction were also calculated for the compounds IVe, IVf, IVj. According to pharmacological results, compound IVl exert the most activity and compound IVc has been found to be least active in this series. The methyl ester derivatives carrying mono halogensubstitutent in the phenyl ring, the activity order is F > Br > Cl. Replacement of the substituted phenyl ring with the pyridine ring increases the activity. PMID- 11204941 TI - 3H-[1,2]Dithiolo[3,4-b]pyridine-3-thione and its derivatives synthesis and antimicrobial activity. AB - A series of 2-substituted isothiazolo[5,4-b]pyridine-3(2H)-thiones, isothiazolo[5,4-b]pyridin-3(2H)-ones, N-substituted 2-sulfanylnicotinamides and the corresponding carbothioamide derivatives were synthesized and evaluated for their antimicrobial activity against several strains of Gram+ and Gram- bacteria and fungi. Chemical syntheses were resumed into a comprehensive cyclic route that enables the reversible conversion for each derivative of the series considered. Among the tested compounds the N-(aralkyl)-2-sulfanylnicotinamides show the highest fungitoxicity (MIC = 1.25-5 microg/ml). The best activity towards Gram positive bacteria was in the range of 2.5-5 microg/ml. Activity against Gram negative bacteria was generally very poor for all compounds. PMID- 11204942 TI - Kinetic spectrophotometric determination of ampicillin and amoxicillin in dosage forms. AB - A kinetic spectrophotometric method has been developed for the determination of ampicillin (I) and amoxicillin (II). The method involves hydrolysis of the antibiotics with 1.0 M HCl, neutralization with 1.0 M NaOH followed by addition of palladium(II) chloride in the presence of 2 M KCl. The produced yellow colour is measured at 335 nm. The proposed method is valid over the concentration range 8-40 microg/ml and 10-40 microg/ml for I and II respectively with minimum detectability of 0.73 microg/ml and 0.76 microg/ml for I and II respectively. The determination of the studied compounds adopting the fixed concentration method is feasible with the calibration equations obtained, but the fixed time method has been found to be more applicable. The proposed method was applied to commercial dosage forms and the results obtained were in good agreement with those given by USP method. PMID- 11204943 TI - Simultaneous determination of benzocaine and cetylpiridinium chloride in tablets by first-derivative spectrophotometric method. AB - A new spectrophotometric method for the simultaneous determination of benzocaine and cetylpiridinium chloride in pharmaceutical tablets, which does not require any preliminary separation or treatment of the samples, is described. The quantitative determination of both drugs was carried out using the first derivative values measured at 231.40 and 310.00 nm for benzocaine and at 220.70 nm for cetylpiridinium chloride using the zero-crossing method. The calibration graphs were linear in the ranges from 10 to 25 mg/l of benzocaine and from 4 to 20 mg/l of cetylpiridinium chloride. The developed method was successfully applied for the assay of pharmaceutical tablets and proved to be simple, sensitive and selective. Thermogravimetric techniques, Karl Fischer and loss on drying were also used for a stoichiometric evaluation of the substances studied. PMID- 11204944 TI - Voltammetric determination of N,N'-dinitrosopiperazine in simulated gastric juice. AB - A voltammetric method has been developed for the determination of N,N' dinitrosopiperazine (DNPZ) in simulated gastric juice. The method is based on measuring the differential pulse polarographic peak produced in pH 3 Britton Robinson buffer. A well defined, diffusion-controlled cathodic wave was obtained at -0.77 V versus Ag/AgCl over the range 0.4-24 microg/ml with minimum detectability (S/N = 2) of 0.072 microg/ml (5 x 10(-7) M). The proposed method was successfully applied to study the possible in vivo production of the nitroso derivatives of piperazine under the standard nitrosation reaction conditions recommended by WHO. The method has some distinct advantages over the reported GC methods. PMID- 11204945 TI - Physico-chemical and solid-state characterization of secnidazole. AB - Secnidazole (hydroxy-2-propyl)-l-methyl-2-nitro-5-imidazole) is an antimicrobic agent. This drug has pharmacological activity against intestinal and hepatic amebiasis, giardiasis and vaginal trichomoniasis. This paper shows the physicochemical parameters of secnidazole determined during a preformulation study. The determination of the apparent partition coefficient and the profile of solubility in dependence of pH demonstrate the basic characteristic of the drug. The dissolution assay was performed to evaluate its behavior in water. For this purpose, a new spectrophotometric method, which was linear from 5 to 15 microg/ml, sensitive, precise, accurate and selective, was validated to assay the bulk drug. The evaluation of higroscopicity revealed that the drug is unstable above 54% of relative humidity. Rheological properties, such as porosity, tapped and bulk densities and percentage of compressibility were calculated. Results show a bad rheological characteristic for this drug. DSC curves do not show any physical interaction between the drug and the excipients in the compatibility studies. PMID- 11204946 TI - 4-Hydroxycoumarin in heterocyclic synthesis. Part III. Synthesis of some new pyrano[2,3-d]pyrimidine, 2-substitute. AB - The synthesis of new [1]benzopyrano[3',4':5,6]pyrano[2,3-d]pyrimidines and related heterocycles has been reported. The key intermediate 2-amino-3-cyano-4 methyl-4H,5H-pyrano[3,2-c][1]benzopyran-5-one (3) was obtained in one pot synthesis from the reaction of 4-hydroxycoumarin and acetaldehyde-malononitrile (2). The antimicrobial screening was performed for some of the synthesized compounds. PMID- 11204947 TI - Synthesis and antimicrobial activity of some new 4-hydroxy-2H- 1,4-benzoxazin 3(4H)-ones. AB - Some 4-hydroxy-2H-1,4-benzoxazin-3(4H)-ones were synthesized and evaluated for their antimicrobial activities against Staphylococcus aureus, Escherichia coli and Candida albicans. Compounds 9, and 10 exhibited the best activity against Candida albicans. PMID- 11204948 TI - Synthesis, anti-inflammatory and antimicrobial activities of new 1,2,4 oxadiazoles peptidomimetics. AB - A new series of 1,2,4-oxadizoles 6a-g have been synthesised in good yields using the peptide synthesis strategy. The prepared compounds were tested for anti inflammatory and antimicrobial activities. The anti-inflammatory activities were determined in the rat paw oedema induced by carrageenin. Compounds 6a, c, f and g (i.v.) significantly inhibited the rat paw oedema induced by carrageenin depending upon the dose employed. The compounds were also evaluated for their in vitro antimicrobial activity. Some compounds were found to have significant activity against Gram positive and Gram negative microorganisms. PMID- 11204949 TI - Quinazoline derivatives with antitubercular activity. AB - 4-Quinazolinol was prepared by the reaction of anthranilic acid and formamide. The hydroxy group was converted into the thiol function by treatment with phosphorus(V)sulfide, and the subsequent alkylation of the thiol group was carried out with alkylhalides under the conditions of phase-transfer catalysis. The structure of the substances was confirmed by 1H, 13C NMR, IR, and MS. Most of the synthesized compounds exhibited antimycobacterial activity against the strains of Mycobacterium tuberculosis, Mycobacerium avium, Mycobacterium fortuitum, Mycobacterium kansasii and Mycobacterium intracellulare. 4-(S Butylthio)quinazoline (3c) was even more active than isoniazide against atypical strains of mycobacteria. PMID- 11204950 TI - Structure-activity relationships for the analgesic activity of gallic acid derivatives. AB - Values of ID50 for a collection of structurally-related gallic acid derivatives have been employed to create a predictive quantitative structure-activity relationship (QSAR) which links structure to values of analgesic activity. The QSAR model developed has substantial predictive power for the design of novel gallic acid derivatives having improved analgesic potency. PMID- 11204952 TI - Nature and Nurture in Epilepsy and Psychiatry: Implications for New Treatment Strategies. Proceedings of a meeting. Oslo, Norway, June-July 2000. PMID- 11204953 TI - Inflammatory bowel disease. PMID- 11204951 TI - Prolidase-activated prodrug for cancer chemotherapy cytotoxic activity of proline analogue of chlorambucil in breast cancer MCF-7 cells. AB - Although prolidase [EC 3.4.13.9] is found in normal cells, substantially increased levels are found in some neoplastic tissues. Because prolidase possesses the ability to hydrolyse imido bonds of various low molecular weight compounds coupled to L-proline, we hypothesized that coupling of L-proline through an imido bond to anticancer drugs might create prodrugs which would be locally activated by tumour-associated prolidase and consequently would be less toxic to normal cells that evoke lower prolidase activity. To test this concept we have synthesized a conjugate of chlorambucil-proline (CH-pro) as a possible prodrug. Treatment of this prodrug with prolidase generated the L-proline and the free drug, demonstrating its substrate susceptibility to prolidase. We have compared several aspects of biological actions of chlorambucil (CH) and its prodrug in breast cancer MCF-7 cells. IC50 values for chlorambucil and for CH-pro in DNA synthesis were found to be 54 and 16 microM, respectively. CH-pro also exhibited a lesser ability to inhibit collagen biosynthesis in breast cancer MCF 7 cells compared to the free drug. The IC50 values for chlorambucil and for CH pro in collagen biosynthesis were found to be about 32 and 80 microM, respectively. This suggests that the targeting of prolidase may serve as a potential strategy for converting antineoplastic prodrugs. PMID- 11204954 TI - Surgical options for ulcerative colitis. PMID- 11204955 TI - Gastric cancer in Iceland. What is the current status? Survival of 193 patients operated on for cure, 1980-1995. AB - OBJECTIVE: The incidence of gastric cancer has been decreasing in the last decades. Nevertheless, gastric cancer is still a substantial health problem in Iceland. The aim of this study was to analyze the survival of patients with gastric cancer operated on for cure. MATERIAL AND METHODS: We reviewed all medical files for above-mentioned patients, operated on at the National University Hospital in Reykjavik and the Quarter District Hospital of Akureyri during 1980-1995. The study was divided into three periods: 1980-1985, 1986-1990 and 1991-1995. The five-year survival for each study period and for the whole group was evaluated. RESULTS: The study group included 193 patients between the ages of 21-96 (median 71). The five-year survival for the whole group was 28% (26% 1980-1985, 22% 1986-1990, 35% 1991-1995). Despite longer survival during the last period, it was not statistically significant (p = 0.16). The major survival factor of gastric cancer was the stage of the disease at diagnosis. A greater number of patients were at stage IA during 1991-1995. The complication rate was rather high or 31% and the hospital mortality was 6.7%. CONCLUSION: The survival of patients with gastric cancer operated on for cure was low in Iceland but comparable to that in other countries. During the last years, the survival has been rising, and fortunately, more were diagnosed at a lower stage of the disease. These operations have a considerable risk and the hospital mortality was substantial. PMID- 11204956 TI - Survival after surgery for gastric cancer in patients over 70 years of age. AB - BACKGROUND AND AIMS: The increase of the elderly population in western societies will result in a considerable increase of gastric cancer patients older than 70 years requiring surgery. However, higher postoperative morbidity and mortality rates after major surgery in the elderly are well recognized. The aim of this study was to evaluate the risk factors of mortality and predictors of survival in elderly patients with gastric cancer. METHODOLOGY: We reviewed the data of the 165 patients evaluated for gastric cancer surgery in the Oulu University Hospital from January 1985 till December 1994 and made a computer analysis. RESULTS: Postoperative mortality was 12% both after all laparotomies and after all resections, and 6% after radical resections. Mortality after radical resection did not associate significantly with any clinical variable but morbidity was associated with the number of coexistent diseases. The median and cumulative 5 year survivals after radical resections were 40 months and 38%. Survival was closely related to diagnostic delay, preoperative loss of weight, two or more coexistent disease, location of tumor, and recurrence in univariate analysis, but multivariate analysis showed only preoperative weight loss and recurrent disease to be independent predictors of survival. CONCLUSIONS: Age alone is not a risk factor for postoperative mortality or a predictor of survival among elderly patients with gastric cancer. Early detection of malignancy and careful preoperative evaluation of the patients referred for resection are needed to improve survival. PMID- 11204957 TI - Clinicopathological study of mucinous gastric carcinoma. AB - BACKGROUND AND AIMS: Mucinous gastric carcinoma (MUC) is relatively a rare subtype of gastric carcinoma, and there has been considerable controversiy over the prognosis of this type of carcinoma. In this study we tried to analyze the clinicopathological differences between MUC and other types of gastric carcinoma (non-MUC) and determine whether MUC is associated with a worse prognosis than non MUC. MATERIAL AND METHODS: We reviewed 645 patients with pathologically confirmed gastric cancer who underwent gastrectomy in our facility during the period from 1975 through 1997. Among them, 20 patients (3.1%) had gastric carcinoma with (MUC), and 625 patients had it without extracellular mucin (non-MUC). In addition, we classified MUC into two groups (well-differentiated type; 7 cases and poorly differentiated type; 9 cases) and analyzed the differences between them. RESULTS: The MUC tumors were more often located in the lower and the upper third of the stomach (MUC: 55% and 25%, non-mUC: 41% and 18%, respectively). The patients with MUC had more serosal invasion (t3 plus t4; MUC: 45%, non-MUC: 18%), more-invasive carcinoma (Type 3 plus 4; MUC: 60%, non-MUC: 36%) and more lymph node involvement (MUC: 45%, non-MUC: 38%) than the patients with non-MUC. The patients with MUC were more advanced in stage at the time of diagnosis (Stage III plus IV; MUC: 50%, non-MUC: 26%) and had a higher peritoneal dissemination rate (MUC: 30%, non-MUC: 12%) and a lower curability rate (MUC: 60%, non-MUC: 78%) than the patients with non-MUC. The mean size of tumors in MUC (7.4 cm) was larger than that of non-MUC (5.5 cm). Therefore, the overall 5-year survival rate for MUC patients (33%) was lower than that for non-MUC patients (64%). There were no significant differences between well-differentiated and poorly differentiated subtypes of MUC except for the curability and peritoneal dissemination rates. CONCLUSIONS: The overall survival rate for patients with MUC was worse than that for patients with non-MUC. The poor prognosis was correlated with more advanced stage at diagnosis and more frequent serosal invasion. These results suggest the need to diagnose patients with MUC in the early stage of cancer and that in the case of the advanced stage, wide excision of the surrounding tissues and aggressive lymph-node dissection will be needed. PMID- 11204958 TI - Pancreatic injuries in children. AB - AIMS: There are several different philosophies in the diagnostics of blunt abdominal trauma (BAT), yet none of them has been shown to be superior, although enhanced computed tomography (CT) and diagnostic ultrasonography (US) seem to be the most used methods today. Treatment of pancreatic injury (PI) in children is a matter of controversy, whether operative treatment is needed and to what extent. MATERIAL AND METHODS: Seventeen pancreatic injuries were found in a retrospective analysis of 111 paediatric patients, aged 2-14 years, who underwent a laparotomy because of BAT, between 1968 and 1995 in Turku University Central Hospital. The number of non-operated BAT patients was calculated as 287. RESULTS: During the past two decades, the number of BATs and operations diminished by more than two thirds, but the number of PIs remained the same. Twelve acute operations led to four pancreatic resections, two external drainages and two explorations. PI was present but not the main reason for operation in four cases. Five PIs were operated on later due to postraumatic pseudocyst of the pancreas. CONCLUSIONS: PI was rare (15%) in laparotomies done because of BAT, operations which have diminished by 74% during the last twenty years. When PI was found, a variety of operative procedures was needed. PMID- 11204959 TI - Abdominal disorders arising from 71 Meckel's diverticulum. AB - BACKGROUND AND AIMS: The study was done to investigate the frequency of Meckel's diverticulum, and its manifestations as the cause of abdominal disorders. MATERIAL AND METHODS: The material consisted of 71 patients with Meckel's diverticulum treated in our hospital during the years 1988-1998. From the material the age and sex were analyzed as well the outcome of patients. The histological findings of diverticulectomies were evaluated. RESULTS: In a retrospective analysis 46 males (65.5%) and 25 females (34.5%) were found. At the same eleven-year study period Meckel's diverticulum was found during 55 out of 3758 appendicectomies (1.5%). The age of patients ranged from 11 months to 87 years (mean 30.4 years). Preoperatively the diagnosis was made in three cases: two patients with TC-99m scanning and one patient with intestinal passage radiography. 46 Meckel's diverticles were asymptomatic, but 25 (34.5%) cases were symptomatic. Nine patients had ulcer in the diverticulum, which was perforated in five cases. Eight patients had intestinal occlusion, five patients had Meckel's diverticulitis, two patients had invagination, and in one case a sharp piece of plastic material had perforated the Meckel's diverticulum. CONCLUSION: Meckel's diverticulum should be searched in the laparotomy due to acute abdomen. It can be the cause of serious abdominal complications. PMID- 11204960 TI - Trends of vascular service in a well defined geographical area in 1990's. AB - BACKGROUND AND AIMS: The treatment policy of vascular surgical patients has undergone changes in the last decade. The aim of this study was to evaluate development of vascular service in a well defined geographical area, the district of Tampere University Hospital. MATERIAL AND METHODS: This population based study is established on the vascular registry. During the eight year period (1990-1997) totally 5019 procedures had been registered, 3363 vascular surgical operations and 1656 endovascular interventions. This data was analysed retrospectively. RESULTS: The annual amount of vascular surgical procedures was in average 959 per million inhabitants and the amount of endovascular procedures 474 per million inhabitants during the period and the trend was slightly increasing. The mean age of surgical patients increased significantly during the eight year period, from 63.6 to 66.6 years, while the mean age of endovascular patients remained fairly stable over the whole period. The proportion of critical limb ischaemia as an indication for surgical procedure increased during the period from 7.3% to 16.6% (p < 0.001). In the same time also the amount of femoropopliteal and femorodistal bypasses as a treatment of CLI increased significantly (p < 0.001). Further, the proportion of surgical procedures compared to the endovascular procedures in the treatment of CLI increased constantly over the 8-year period from 25% to 61% (p < 0.001). The absolute amount of access surgery increased over the period and the mean age of these patients increased significantly. The median of hospital stay decreased during the eight year period in the surgical group from 9 days to 6 days and in the endovascular group from 2 days to 1 day. CONCLUSIONS: The main changes have been the increased mean age of patients, their shortened hospital stay and the increasing surgical activity on patients with CLI and the larger number of patients with need for vascular access. PMID- 11204961 TI - Long term prognosis of medullary thyroid carcinoma in 39 patients. AB - BACKGROUND AND AIMS: Thyroidectomy and radical cervical lymph node dissection have been suggested as primary and secondary operations aimed at achieving biochemical cure in cases of medullary thyroid carcinoma (MTC). The purpose of this study was to find out behaviour of MTC in long-term follow-up, and to estimate possible difference in biological virulence between sporadic MTC and MTC in MEN2A. MATERIAL AND METHODS: From 1967 through 1994, 39 patients with MTC, including 9 patients with hereditary disease, were operated on at the Second Department of Surgery, Helsinki University Central Hospital. Enlarged lymph nodes were dissected selectively. The main outcome measure was carcinoma-specific survival. RESULTS: In sporadic MTC, ten-year carcinoma-specific survival was 57.9% (95% CI 39.1%-76.7%) and ten-year survival after reoperation due to lymphatic node recurrence was 51.4% (CI 18.7%-84.2%). The presence of distant metastases at diagnosis (p = 0.0001) and extrathyroidal growth of the primary tumor (p = 0.0008) were independent predictors of carcinoma-specific survival in the Cox model. The risk ratio of sporadic MTC to MTC in MEN2A was 5.40 (CI 0.67 43.2) after adjusting the survival time for the size of the primary tumor. CONCLUSION: Distant metastases and the local extrathyroidal extent of the primary tumor have a significant effect on the prognosis of MTC, lymphatic node metastases and other clinical factors being less important. The biological virulence of sporadic MTC may be clinically significantly higher than that of MTC in MEN2A. PMID- 11204962 TI - Results of surgical treatment of unresolved Osgood-Schlatter lesion. AB - BACKGROUND AND AIMS: We present our experience with surgical treatment of unresolved, painful, late Osgood-Schlatter disease. MATERIAL AND METHODS: In 70 operations performed in 67 patients (in three bilaterally) an ossicle under the distal patellar tendon was removed in 62 cases. In eight cases, excision of the prominent tibial tubercle and/or drilling of the epiphysis was performed. Additional procedures, such as rasping of the uneven anterior tibial surface, excision of inflammed bursa or the devitalized portion of the tendon, were done 21 times. Most patients were athletes or physically active young people. The mean age was 19.6 years. 54 operations were done on males and 16 on females. They had been followed preoperatively for 18 months and after surgery 2.2 years. RESULTS: The final results were excellent or good in 56, moderate in 9, poor in 3 and unknown in 2 cases. CONCLUSIONS: Osgood-Schlatter's disease may leave an ossicle under the distal patellar tendon, a prominent tibial tubercle or an uneven surface of anterior superior tibia. These may lead to pain and disability due to recurrent injuries or athletic exercises. Surgical treatment gives good results in chronic unresolved cases. PMID- 11204963 TI - Posttraumatic limb shortening: treatment with the Ilizarov distraction device. AB - BACKGROUND AND AIMS: Limb length inequality is not only a cosmetic problem, it is also a functional concern. The aim of the study was to analyse the cases of limb lengthening after their posttraumatic shortening. The study design is descriptive and comparative. MATERIAL AND METHODS: During the years 1979-1994 14 patients between 4-18 years of age were treated. Limb shortening was the result of premature closure of physeal plate and severe traumas with large bone defects. Ilizarov external devices for limb lengthening were used. The lengthening index was counted. The patients were divided into four groups: minor lengthening, bone transport, femoral lengthening, lengthening with using bone allografting. RESULTS: In group I the lengthening index was 29.9 days per centimetre (d/cm), in group II 21.7 d/cm, in group III 33.5 d/cm, in group IV 20.5 d/cm. The complication rate was 28%: 14% "minor" and 14% "major"-stiffness, wound necrosis. None of them affected the final result. In almost all cases the lengthening index was below 30 d/cm. CONCLUSIONS: The result of limb lengthening is not predictable in every separate case. Multiple lengthening may act on bone regeneration capacity. PMID- 11204964 TI - Study of straight metatarsal osteotomy for the treatment of plantar callosities. AB - BACKGROUND AND AIMS: [corrected] To evaluate the outcome of transverse distal metatarsal osteotomies for intractable plantar callosity without hammer toe deformity and associated toe corns. MATERIAL AND METHODS: Twenty-five plantar callosities were treated in 19 feet of 13 patients (mean age 48 years, 5 male, 8 female) with transverse distal metatarsal osteotomy. RESULTS: Twenty-four of the osteotomies united primarily, one after revision. After a 7-year follow-up, 23 of the callosities had healed, two of them after an oblique reosteotomy. Eight hammer toe deformities had developed in the involved rays of four feet. Eight plantar callosities had developed outside the operated rays in five feet. Hallux valgus was a frequent finding in both operated and non-operated feet. CONCLUSION: It seems that transverse distal metatarsal osteotomy is an effective treatment of intractable plantar callosities. Harmful hammer toe deformities and transfer lesions below adjacent metatarsal heads tend to develop over time. PMID- 11204965 TI - Tourniquet-induced enmg changes in arthroscopic anterior cruciate ligament reconstruction. A comparison of low and high-pressure tourniquet systems. AB - BACKGROUND AND AIMS: The use of a tourniquet during surgery is associated with a risk of neurological disorders. We compared whether a new tourniquet system using low pressure (250 mmHg) is safer than a standard tourniquet system using higher inflation pressure (350 mmHg). MATERIALS AND METHODS: Thirty-one patients (ASA I II), ages 16-48 years, were studied with ENMG preoperatively and 3 weeks postoperatively following arthroscopic anterior cruciate ligament reconstruction. Tourniquet times varied between 30 and 146 min. RESULTS: Postoperative slowing of motor and sensory conduction was observed, as well as an increase of the minimum peroneal F-response and tibial H-reflex latencies. The sensory amplitude of the sural nerve decreased. Vastus medialis of the quadriceps femoris muscle showed a reduced interference pattern in ENMG in maximal voluntary effort postoperatively. No differences were found in measured results between the low and high pressure tourniquet systems. CONCLUSIONS: Slight postoperative ENMG alterations were demonstrated but the use of both tourniquet systems is safe within the limit of tourniquet times of less than 2 h. PMID- 11204966 TI - Treatment of infection and non-union after bilateral complicated proximal tibial fracture. AB - BACKGROUND AND AIMS: Complicated tibial fractures form a great challenge for orthopaedic surgeons. Non-unions and infections are more common in complicated than in closed fractures. In the present study, we describe a patient case treated for non-union combined to chronic osteomyelitis after bilateral open proximal tibial fractures. MATERIAL AND METHODS: A female patient born in 1946 was multi-traumatised, when a car hit her as a pedestrian. She went through multiple operations of both tibias due to bilateral complicated proximal fractures. Fractures were stabilised at first with internal fixation, which had to be changed to external fixation due to infection of both sides. During the last operative step a commercial bone graft based on hydroxyapatite and bovine type I fibrillar collagen/tricalcium phosphate ceramic (Collagraft) mixed with autogenous bone marrow was applied. RESULTS: Fractures united after 28 (right tibia) and 22 (left tibia) months of follow-up. At the final follow-up visit 55 months after the initial accident patient walked without any aid and showed no signs of an infection. CONCLUSIONS: The use of commercial mixed xeno-/autogenous bone graft may provide a feasible alternative in complicated chronic non-unions of the tibia even when an infection is present, especially when autogenous bone is not easily available after previous attempts of bone grafting. PMID- 11204967 TI - How to do sentinel node biopsy in breast cancer. PMID- 11204968 TI - A new method for surgical consultations with videoconference. AB - BACKGROUND: The aim of our prospective study was to examine the technical ability and the medical suitability of a realtime teleconferencing system in surgical consultations. METHOD: A personal computer-based-videoconferencing system was used over an architecture of the IP (Internet Protocol) over ATM (Asynchronous Transfer Mode) area network connecting Satakunta Central Hospital, Pori with a health center in the community of Noormarkku (15 km apart from Pori). A document camera was used for transfering the radiographs and paper documents. The material consisted of 50 patients who needed surgical consultation. The patients were examined by a physician in the health center of Noormarkku, and the surgeon interviewed and observed the physical examination with the aid of teleconference. RESULTS: Technically the videoconferencing system functioned reliably, and the visual quality of the videopicture was good after more powerful personal computers (Pentium II with a 266 MHz prosessor and 64 Megabits RAM-memory) were changed for the videoconferencing system. All patients, except one, saved the travelling to the face-to-face appointment because they got a definite decision of the treatment already at the videoconsultation. According to the opinion of the consulting surgeon, the decision which was made in the teleconference was good or very good, except in one case very poor. The physicians of the health centers were satisfied both with the decisions of the treatment of their patients and with the educational effect of a consultation where two physicians are present at the same time. All patients thought that it was good to be in consultation with two doctors. CONCLUSION: Surgical videoconsultations are a reliable method and a real alternative to sending a patient to a distant place for consultation. PMID- 11204970 TI - Insertions, substitutions, and the origin of microsatellites. AB - This paper uses data from the Human Gene Mutation Database to contrast two hypotheses for the origin of short DNA repeats: substitutions and insertions that duplicate adjacent sequences. Because substitutions are much more common than insertions, they are the dominant source of new 2-repeat loci. Insertions are rarer, but over 70% of the 2-4 base insertion mutations are duplications of adjacent sequences, and over half of these generate new repeat regions. Insertions contribute fewer new repeat loci than substitutions, but their relative importance increases rapidly with repeat number so that all new 4-5 repeat mutations come from insertions, as do all 3-repeat mutations of tetranucleotide repeats. This suggests that the process of repeat duplication that dominates microsatellite evolution at high repeat numbers is also important very early in microsatellite evolution. This result sheds light on the puzzle of the origin of short tandem repeats. It also suggests that most short insertion mutations derive from a slippage-like process during replication. PMID- 11204969 TI - Developmental expression of the 412 retrotransposon in natural populations of D. melanogaster and D. simulans. AB - We analysed the pattern of expression of retrotransposon 412 through developmental stages in various populations of Drosophila simulans and D. melanogaster differing in 412 copy number. We found that the 412 expression pattern varied greatly between populations of both species, indicating that such patterns were not entirely species-specific. In D. simulans, total transcripts increased with number of 412 copies in the chromosomes when this number was low, and then decreased for high copy numbers. D. melanogaster, which has a higher 412 copy number than D. simulans, had overall a lower global 412 expression, but again showed variation in 412 expression pattern between populations. These results suggest that in populations of D. simulans with low 412 copy number, the expression pattern of this element depends not only on copy number but also on host cellular regulatory sequences near which the elements were inserted. In D. simulans populations with high copy number overall transcription was on the contrary globally repressed, as observed in D. melanogaster. A population from Canberra (Australia) which had a very high 412 copy number was found to be associated with very high expression of 412 over all developmental stages, suggesting that the above 412 expression regulation processes are overcome in this population sample. The analysis of hybrids between geographically distinct populations of D. simulans showed that 412 expression was trans-regulated differently according to developmental stages, implying complex interactions between the 412 element and stage-specific host genes. PMID- 11204971 TI - Growth temperature and genetic variability of wing dimensions in Drosophila: opposite trends in two sibling species. AB - Thirteen linear wing dimensions were measured in 10 isofemale lines of Drosophila melanogaster and D. simulans grown at seven constant temperatures from 12 to 31 degrees C. Within-line (environmental) variability, estimated by the within-line coefficient of variation (CVw), exhibited similar variation patterns in the two species, that is higher values at extreme (low or high) temperatures. The magnitude of variation was, however, greater in D. simulans, which appears to be more responsive to thermal change. A clear hyperbolic relationship between trait mean value and CVw was also observed in both species, arising from measurement errors which are relatively more pronounced on shorter traits. Genetic variability was analysed by considering both the genetic CV (CVg, evolvability) and isofemale line heritability (intraclass correlation). Both parameters provided independent information, as shown by a lack of correlation between them. Moreover, CVg was negatively correlated with trait mean value, while heritability showed a positive correlation. With respect to thermal environment, both parameters exhibited similar reaction patterns which contrasted the two species. Genetic variability in D. melanogaster followed a convex reaction norm, with higher values at extreme (high or low) temperatures, and this observation agrees with previous independent investigations. Surprisingly, D. simulans revealed an opposite pattern, with a maximum genetic variability in the middle of the range. Such data point to the danger of drawing general conclusions from the analysis of a single species. PMID- 11204972 TI - Evolution of reduced pre-adult viability and larval growth rate in laboratory populations of Drosophila melanogaster selected for shorter development time. AB - Four large (n > 1000) populations of Drosophila melanogaster, derived from control populations maintained on a 3 week discrete generation cycle, were subjected to selection for fast development and early reproduction. Egg to eclosion survivorship and development time and dry weight at eclosion were monitored every 10 generations. Over 70 generations of selection, development time in the selected populations decreased by approximately 36 h relative to controls, a 20% decline. The difference in male and female development time was also reduced in the selected populations. Flies from the selected populations were increasingly lighter at eclosion than controls, with the reduction in dry weight at eclosion over 70 generations of selection being approximately 45% in males and 39% in females. Larval growth rate (dry weight at eclosion/development time) was also reduced in the selected lines over 70 generations, relative to controls, by approximately 32% in males and 24% in females. However, part of this relative reduction was due to an increase in growth rate of the controls populations, presumably an expression of adaptation to conditions in our laboratory. After 50 generations of selection had elapsed, a considerable and increasing pre-adult viability cost to faster development became apparent, with viability in the selected populations being about 22% less than that of controls at generation 70 of selection. PMID- 11204973 TI - Comparison of genetic variability and parentage in different ploidy classes of the Japanese oyster Crassostrea gigas. AB - Chemical treatments with cytochalasin B were used to induce triploidy in the progeny of a mass fertilization of 3 male and 7 female Crassostrea gigas parents. Triploids were produced either by retention of the first (meiosis I (MI) triploids) or the second (meiosis II (MII) triploids) polar bodies. These animals, together with their diploid siblings, were divided for two experiments. One set was used to compare physiological performance, and the other set deployed to compare growth in two different natural environments. For both experiments, genetic variability in different ploidy classes was estimated using three microsatellite loci and eight allozyme loci. The microsatellite loci were highly polymorphic, allowing independent confirmation of ploidy status and the unambiguous identification of parentage for each oyster. Significant differences in parentage were found between ploidy classes, despite the fact they originated from the same mass fertilization. This indicates that the assumptions of a common genetic background among random samples of animals taken from the same mass fertilization may not be generally valid. Knowledge of parentage also allowed the more accurate scoring of allozyme loci. As expected, triploids were found to be significantly more polymorphic than diploids. However, MI triploids were not significantly more polymorphic than MII triploids. MII triploid genotypes were used to estimate recombination rates between loci and their centromeres. These rates varied between 0.29 and 0.71, indicating only moderate chiasma interference. PMID- 11204974 TI - Separate effects of triploidy, parentage and genomic diversity upon feeding behaviour, metabolic efficiency and net energy balance in the Pacific oyster Crassostrea gigas. AB - Triploid oysters were induced using cytochalasin B upon retention of either the first (meiosis I triploids) or the second (meiosis II triploids) polar body in embryos from a single cohort derived from mixed parentage. Allozyme and microsatellite assays enabled the confirmation of both parentage and triploidy status in each oyster. Comparison of meiosis I triploids, meiosis II triploids and diploid siblings established that improved physiological performance in triploids was associated with increased allelic variation, rather than with the quantitative dosage effects of ploidy status. An unidentified maternal influence also interacted with genotype. Among full sibs, allelic variation measured as multi-locus enzyme heterozygosity accounted for up to 42% of the variance in physiological performance; significant positive influences were identified upon feeding rate, absorption efficiency, net energy balance and growth efficiency (= net energy balance divided by energy absorbed). Whilst allelic variation was greater in both meiosis I and meiosis II triploids than in diploid siblings, both allelic variation and net energy balance were highest in triploids induced at meiosis I. This suggests that it may be preferable to induce triploidy by blocking meiosis I, rather than meiosis II as has traditionally been undertaken during commercial breeding programmes. PMID- 11204975 TI - Quantitative genetic models for the balance between migration and stabilizing selection. AB - The evolution of a quantitative trait subject to stabilizing selection and immigration, with the immigrants deviating from the local optimum, is considered under a number of different models of the underlying genetic basis of the trait. By comparing exact predictions under the infinitesimal model obtained using numerical methods with predictions of a simplified approximate model based on ignoring linkage disequilibrium, the increase in the expressed genetic variance as a result of linkage disequilibrium generated by migration is shown to be relatively small and negligible, provided that the genetic variance relative to the squared deviation of immigrants from the local optimum is sufficiently large or selection and migration is sufficiently weak. Deviation from normality is shown to be less important by comparing predictions of the infinitesimal model with a model presupposing normality. For a more realistic symmetric model, involving a finite number of loci only, no linkage and equal effects and frequencies across loci, additional changes in the genetic variance arise as a result of changes in underlying allele frequencies. Again, provided that the genetic variance relative to the squared deviation of the immigrants from the local optimum is small, the difference between the predictions of infinitesimal and the symmetric model are small unless the number of loci is very small. However, if the genetic variance relative to the squared deviation of the immigrants from the local optimum is large, or if selection and migration are strong, both linkage disequilibrium and changes in the genetic variance as a result of changes in underlying allele frequencies become important. PMID- 11204976 TI - Maintenance of genetic variation in phenotypic plasticity: the role of environmental variation. AB - We study genetic variation in phenotypic plasticity maintained by a balance between mutation and weak stabilizing selection. We consider linear reaction norms allowing for spatial and/or temporal variation in the environments of development and selection. We show that the overall genetic variation maintained does not depend on whether the trait is plastic or not. The genetic variances in height and slope of a linear reaction norm, and their covariance, are predicted to decrease with the variation in the environment. Non-pleiotropic loci influencing either height or slope are expected to decrease the genetic variance in slope relative to that in height. Decrease in the ratio of genetic variance in slope to genetic variance in height with increasing variation in the environment presents a test for the presence of loci that only influence the slope, and not the height. We use data on Drosophila to test the theory. In seven of eight pair wise comparisons genetic variation in reaction norm is higher in a less variable environment than in a more variable environment, which is in accord with the model's predictions. PMID- 11204977 TI - Power of quantitative trait locus mapping for polygenic binary traits using generalized and regression interval mapping in multi-family half-sib designs. AB - A generalized interval mapping (GIM) method to map quantitative trait loci (QTL) for binary polygenic traits in a multi-family half-sib design is developed based on threshold theory and implemented using a Newton-Raphson algorithm. Statistical power and bias of QTL mapping for binary traits by GIM is compared with linear regression interval mapping (RIM) using simulation. Data on 20 paternal half-sib families were simulated with two genetic markers that bracketed an additive QTL. Data simulated and analysed were: (1) data on the underlying normally distributed liability (NDL) scale, (2) binary data created by truncating NDL data based on three thresholds yielding data sets with three different incidences, and (3) NDL data with polygenic and QTL effects reduced by a proportion equal to the ratio of the heritabilities on the binary versus NDL scale (reduced-NDL). Binary data were simulated with and without systematic environmental (herd) effects in an unbalanced design. GIM and RIM gave similar power to detect the QTL and similar estimates of QTL location, effects and variances. Presence of fixed effects caused differences in bias between RIM and GIM, where GIM showed smaller bias which was affected less by incidence. The original NDL data had higher power and lower bias in QTL parameter estimates than binary and reduced-NDL data. RIM for reduced-NDL and binary data gave similar power and estimates of QTL parameters, indicating that the impact of the binary nature of data on QTL analysis is equivalent to its impact on heritability. PMID- 11204978 TI - A DNA marker for the duplicated cytosolic PGI genes in sheep's fescue (Festuca ovina L.). AB - Active duplicate PgiC genes in sheep's fescue, Festuca ovina, are associated with a PCR marker of specific length (about 370 bp, of which 231 are in an intron). Using this marker, the frequency of plants with duplicate genes is estimated to be about 10% in a population from southern Sweden. The close molecular similarity between the electrophoretically different duplicated genes is in accordance with the conclusion reached earlier that they are indeed alleles at the same locus. PMID- 11204979 TI - Estimation of microsatellite mutation rates in Drosophila melanogaster. AB - Microsatellite mutations were studied in a set of 175 mutation accumulation lines, all of them independently derived from a completely homozygous population of Drosophila melanogaster and maintained under strong inbreeding during 80 generations. We assayed 28 microsatellites and detected two mutations. One mutation consisted of a single addition of a dinucleotide repeat and the other was a deletion of five trinucleotide repeats. The average mutation rate was 5.1 x 10(-6), in full agreement with previous estimates from two different sets of mutation accumulation lines. PMID- 11204980 TI - Diagnosis of esophagogastric tumors. AB - The incidence of esophageal tumors, and of adenocarcinoma in particular, has risen markedly in recent years in the developed countries. The use of a variety of histopathological and biological markers is now offering promising prospects for the future. Vertical tumor invasion, intratumoral microvessel density, antimucin monoclonal antibodies, flow cytometry, telomerase activity, and overexpression of cyclin D1 have been correlated with the staging and prognosis of esophageal carcinomas. By combining these markers with Lugol staining, a practical new method of staging esophageal tumors may become available in the coming years. As is well known, Barrett's mucosa is a preneoplastic condition. Discussions in the literature concerning short forms of Barrett's esophagus and their relationship to inflammation of the gastric cardia appear to describe two different scenarios--a gastroesophageal reflux condition for short forms of Barrett's esophagus, and an inflammatory phenomenon (perhaps unrelated to Helicobacter pylori infection) for inflammation of the gastric cardia. Cost benefit studies of follow-up procedures in Barrett's esophagus have yet to be conducted, and considerable efforts--mainly using biological markers--are being made to identify those patients who are at greatest risk. Although the frequency of gastric tumors has declined in recent years, many as yet unclear aspects of these tumors have been studied. Technological progress has not led to substantial changes in the diagnostic procedures used, although autofluorescence methods and three-dimensional reconstruction have been analyzed. Laparoscopy, preferably combined with the use of ultrasound probes, may be a valuable tool for staging. The suggestion that endoscopy should be avoided in young patients (the "treat but do not scope" approach) has been seriously questioned, as it may lead to early cancer being overlooked. There is thought to be an intermediate stage of gastric cancer (between the early and advanced stages) in which the muscularis propria, but not the serosa, is invaded. Endoscopic ultrasonography is becoming increasingly established as a basic tool for the staging of gastric cancer. Gastric MALT lymphoma can be cured by H. pylori eradication therapy in many cases, but there is still uncertainty regarding the limitations of this approach. PMID- 11204981 TI - Carcinoid tumor of the choledochus mimicking a bile-duct stone during endoscopic ultrasonography and endoscopic retrograde cholangiography. PMID- 11204982 TI - Secondary aortoduodenal fistula mimicking submucosal tumor. PMID- 11204983 TI - Nonvariceal upper gastrointestinal bleeding. AB - Gastroduodenal ulcerations still account for the majority of nonvariceal gastrointestinal hemorrhage. The causative roles of Helicobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) are still being discussed, but the role of H. pylori appears less significant in the complicated ulcers, while NSAIDs are increasingly implicated. The two factors do not appear to potentiate each other, and some data suggest that H. pylori should not be eradicated in the context of an NSAID-related ulcer hemorrhage. The role of triage and risk assessment was highlighted in several of last year's publications, and increasing attention has been given to the cost aspects of peptic ulcer bleeding. There have been few comparative therapeutic trials, but several reports from Japan make a case for ethanol injection as an alternative to other injection agents. However, a randomized comparative trial is needed to further define the role of this technique. Radiological embolization techniques and minimally invasive surgery are increasingly becoming viable options in patients with complex cases, and a multidisciplinary approach is perhaps even more crucial today than ever before. PMID- 11204984 TI - Small-intestinal endoscopy. AB - A small imaging capsule without cables, wires, or external connections has been developed for exploration of the small bowel. This swallowable device is propelled by peristalsis through the intestinal tract, and transmits data to a nearby receiver that captures video images on a regular basis. This technology will soon be available throughout the world, and it promises to revolutionize deep endoscopy of the small bowel. Sonde enteroscopy will be laid to rest forever. There continues to be considerable interest in the use of push enteroscopy in the investigation of obscure gastrointestinal bleeding. Physicians are beginning to rely more on intraoperative enteroscopy, because of its high degree of accuracy and its ability to provide visualization of the entire small bowel in selected patients in whom the bleeding source cannot be diagnosed, but who require blood transfusions. PMID- 11204985 TI - Therapeutic biliary endoscopy. AB - Therapeutic biliary endoscopy is continuing to evolve; some small but important developments were seen during the last year. Competing techniques are continuing to develop. PMID- 11204987 TI - Colon polyps and cancer. AB - During 1999-2000, a number of important issues related to endoscopy and colorectal polyps and cancer were investigated. Several papers consider whether flat adenomas with high malignant potential are as common in the West as in Japan. Clinical series indicate that signs of rectal bleeding are more predictive of colorectal cancer than gastrointestinal symptoms. Colonoscopy is more accurate than double-contrast barium enema for detecting polyps, and virtual colonoscopy is a promising new diagnostic and screening technique. Primary prevention dietary studies using adenoma recurrence as an end point yield negative results. Surveillance colonoscopy protects individuals in families with hereditary nonpolyposis colorectal cancer, but gastroenterologists continue to perform cancer surveillance in patients with ulcerative colitis in an inconsistent manner. Screening for colorectal neoplasia with fecal occult blood tests and flexible sigmoidoscopy is being better defined and promoted, although many now advocate direct colonoscopy screening based on increasing indirect evidence of efficacy. Better methods of treating large sessile neoplasms are being developed and evaluated, and follow-up surveillance for adenoma patients increasingly is being tailored to individual patient risk. PMID- 11204986 TI - Therapeutic pancreatic endoscopy. AB - Therapeutic endoscopy in pancreatitis has included biliary or pancreatic sphincterotomy, or both, for microlithiasis and sphincter dysfunction. Alternatively, endoscopic treatment has been used to treat ductal disruption, including external or internal fistulas (high amylase effusions, pancreatic ascites, pancreaticoenteric communications, or pseudocysts). Finally, endoscopy has been used to treat obstructive disease, including both stones and strictures. This article reviews the state of the art in this field over the past year. Unfortunately, this is an area in which the appropriate approaches are still poorly defined, and prospective studies randomly assigning patients to endoscopic treatment in comparison with medical or surgical therapy remain few and far between. PMID- 11204988 TI - Diagnostic laparoscopy. AB - The value of surgical laparoscopy for various therapeutic interventions has been well established. In recent years, the interest of gastroenterologists in this method has revived, since laparoscopy can provide additional information for the staging of oncological and liver diseases. The introduction of miniature lenses may have contributed to this process, and an increasing number of physicians are using minilaparoscopy due to its safety and easy handling. Surgical studies have mainly focused on the evaluation of laparoscopic ultrasound for the detection of liver and lymph-node metastases. In specialized centers, laparoscopic ultrasound is also used for the estimation of locoregional pancreatic tumor spread, but the diagnostic impact of the method, particularly in colorectal carcinoma, still remains to be determined. Remarkably, the number of publications from gastroenterology departments has tended to increase in comparison with last year's review. PMID- 11204989 TI - Effect of variable stiffness colonoscopes on cecal intubation times for routine colonoscopy by an experienced examiner in sedated patients. AB - BACKGROUND AND STUDY AIMS: Variable-stiffness colonoscopes allow passage of the rectosigmoid colon in a flexible mode, followed by stiffening to prevent looping. This feature might allow faster cecal intubation. PATIENTS AND METHODS: Consecutive patients without previous colonic or rectal resection, inflammatory bowel disease, or anticipated need for either a pediatric or standard insertion tube were evaluated. Four Olympus colonoscopes, including a standard "adult" insertion-tube diameter variable-stiffness colonoscope (VSA), a pediatric variable-stiffness colonoscope (VSP), a standard "adult" colonoscope (CF-140) (SA), and a standard "pediatric" colonoscope (PCF-140) (SP) were used in rotation. RESULTS: Among 358 consecutive patients, 99.2% of exams were complete to the cecum. The stiffening device was activated in 61% and 80% of the adult and pediatric variable-stiffness examinations, respectively. The examiner judged the device to be very useful, somewhat useful, and of no help in 46%, 44%, and 10% of VSA colonoscope examinations and 55%, 33%, and 12% of VSP colonoscope examinations. However, the mean cecal insertion time was 4.04 minutes, with no difference between the four colonoscopes (P=0.98). The percentage of intubations in < 2 minutes was 15.4%, 2-3 minutes 25.9%, 3-4 minutes 19.1%, 4-5 minutes 16.0%, and >5 minutes 23.7%, with no significant difference between the colonoscopes. CONCLUSIONS: Variable-stiffness colonoscopes were frequently judged useful by an experienced examiner but did not impact cecal intubation times in sedated patients. Additional studies by other experienced and inexperienced examiners, as well as evaluation of additional technical improvements and evaluation in unsedated patients, are needed. PMID- 11204990 TI - Clinical results and development of variable-stiffness video colonoscopes. AB - BACKGROUND AND STUDY AIMS: This study was designed to assess the usefulness of variable-stiffness video colonoscopes, compared with conventional videoscopes. PATIENTS AND METHODS: The first prototype XCF-QAY1 and the latter prototype XCF Q240A1 used in this study can be varied to 4 levels of stiffness of tube insertion during examination. In 352 consecutive colonoscopic examinations performed using these and two conventional scopes, the following data were recorded: time for intubation to the cecum, frequency of changes in the patients' posture, frequency of abdominal pressure attempts, and pain score. The degree of stiffness of the insertion tube and the examiners' impressions score were recorded only in procedures where the variable-stiffness scopes were used. RESULTS: There was no significant difference between colonoscopes in the pain score. Total colonoscopy rate was 97.4%. The frequency of usage of the varying stiffness control in the colon according to site was as follows: descending colon, 57.3%; transverse colon, 32.8%, sigmoid colon, 7.6%; and ascending colon, 2.3%. A significant difference in the mean time for intubation to the cecum between the XCF-Q240A1 and conventional scopes was observed. Moreover, there were significant differences in the frequency of abdominal pressure attempts and changes in the patient's posture between conventional scopes and the new scopes. CONCLUSIONS: These results suggest that only one scope, the XCF-Q240A1, is needed for any colonic examination by any examiner. PMID- 11204991 TI - The variable-stiffness colonoscope: "too stiff or not too stiff, that is the question"--a new twist to the plot. PMID- 11204992 TI - Lugol chromoendoscopy for esophageal squamous cell cancer. PMID- 11204993 TI - Ulcer and gastritis. AB - Recent progress in the area of ulcer and gastritis is still dominated by findings and reports on Helicobacter pylori and nonsteroidal anti-inflammatory drugs, which in turn are the two major causes of peptic ulcers. Although the prevalence of H. pylori is declining in most developed countries, it is still contributing to a significant proportion of peptic ulcers globally. The interrelationship of H. pylori gastritis in patients with gastroesophageal reflux has become more apparent. H. pylori-induced gastric body gastritis is associated with reduced acid production, and thus with reduced reflux and esophagitis. The controversies regarding the interactions between H. pylori and NSAIDs have still not been settled. With the availability of the new COX-2-specific inhibitors, the current scenario of NSAID-related gastroduodenal complications will certainly change. Short-term usage of these agents has significantly reduced the incidence of endoscopic ulcers, but the benefits in terms of clinical outcomes, such as bleeding or perforation, remain to be determined. This review summarizes the recent literature on peptic ulcer and gastritis. PMID- 11204994 TI - An old lady with pencil-thin stool. PMID- 11204995 TI - Two cases of colonic adenomatous polyps accompanied by a migrated surgical suture. AB - A 56-year-old man and a 70-year-old woman, with histories of left colectomy and appendectomy respectively, were admitted to our hospital. In both cases, colonoscopy showed a pedunculated colonic polyp in the ascending colon, and a silk suture became visible in the stalk during polypectomy. The histological diagnosis was adenoma. These two cases constitute the first report of colonic adenomatous polyps accompanied by suture migration. PMID- 11204996 TI - Small-bowel occlusion after operative laparoscopy: our experience and review of the literature. AB - Bowel complications as a consequence of laparoscopic surgery are usually due to direct injuries; on the other hand, bowel occlusion is a rarely described event. We have retrospectively analyzed our data in this field. Out of 2652 laparoscopies performed between July 1996 and March 2000, three cases of small bowel occlusion were observed. Two cases were due to bowel hernia through a 5-mm trocar port incision, the third was a consequence of an adhesion between the ileum and lost fragment of myoma. Two cases were treated laparoscopically, while in the third a laparotomy was required. At the time of writing, all the patients are well after a mean follow-up of 6 months. It appears important to also perform closure of the fascia and peritoneum after a 5-mm trocar port incision where there has been extensive manipulation. PMID- 11204997 TI - Biliopancreatic fistulas complicating pancreatic pseudocysts: a report of three cases demonstrated by endoscopic retrograde cholangiopancreatography. AB - Three patients were found to have fistulation of the pancreatic and common bile ducts, complicating chronic pancreatitis in one patient and acute pancreatitis in two patients. Closure of the fistula was achieved with biliary and pancreatic stenting in one patient; the other two patients were treated surgically because endoscopic treatment had failed. The clinical and radiological features of this exceptional complication are presented, with a brief review of the topic. PMID- 11204998 TI - Does the use of propofol require a specialist anesthetist? PMID- 11204999 TI - Biliocutaneous fistula following biliary stent migration. PMID- 11205000 TI - 98 unusual cases and technical notes. PMID- 11205001 TI - Sengstaken balloon tamponade for life-threatening pouch hemorrhage after laparoscopic gastric banding. PMID- 11205003 TI - Conjugated organometallic polymers containing Vollhardt's cyclobutadiene complex: aggregation and morphologies. AB - Organometallic polymers were prepared by acyclic diyne metathesis (ADIMET) or by Pd-catalyzed coupling of 1,3-diethynylcyclobutadiene(cyclopentadienyl)cobalt with a suitably substituted diiodobenzene. The polymers obtained by Heck coupling show a degree of polymerization (Pn) of 20-60. The monomers for ADIMET were made by the Pd-catalyzed coupling of [1,3-bis(trimethylsilylethynyl)-2,4 bis(trimethylsilyl)cyclobutadiene](cyclopentadienyl)cobalt to 1-bromo-2,5-dialkyl 4-propynylbenzenes in the presence of KOH in yields of 40-48%. The monomers carry hexyl, ethylhexyl, and (S)-3,7-dimethyloctyl side chains. Polymerization of the propynylated monomers furnishes organometallic polymers with a Pn of up to 230 arylene-ethynylene units. The polymers were fully characterized by polarizing microscopy, transmission electron microscopy, circular dichroism, differential scanning calorimetry, and X-ray diffraction (XRD). They show nematic, lyotropic liquid crystalline phases as well as chiroptical properties from which aggregation in poor solvents and in the solid state can be concluded. Lamellar or irregular honeycomb-shaped morphologies in these organometallic polymers can be detected by electron microscopy. PMID- 11205002 TI - A systematic examination of the morphogenesis of calcium carbonate in the presence of a double-hydrophilic block copolymer. AB - In this paper, a systematic study of the influence of various experimental parameters on the morphology and size of CaCO3 crystals after room-temperature crystallization from water in the presence of poly(ethylene glycol)-block poly(methacrylic acid) (PEG-b-PMAA) is presented. The pH of the solution, the block copolymer concentration, and the ratio [polymer]/[CaCO3] turned out to be important parameters for the morphogenesis of CaCO3, whereas a moderate increase of the ionic strength (0.016 M) had no influence. Depending on the experimental conditions, the crystal morphologies can be tuned from calcite rhombohedra via rods, ellipsoids or dumbbells to spheres. A morphology map is presented which allows the prediction of the crystal morphology from a combination of pH, and CaCO3 and polymer concentration. Morphologies reported in literature for the same system but under different crystallization conditions agree well with the predictions from the morphology map. A closer examination of the growth of polycrystalline macroscopic CaCO3 spheres by TEM and time-resolved dynamic light scattering showed that CaCO3 macrocrystals are formed from strings of aggregated amorphous nanoparticles and then recrystallize as dumbbell-shaped or spherical calcite macrocrystal. PMID- 11205004 TI - Simple syntheses, structural diversity, and Tishchenko reaction catalysis of neutral homoleptic rare earth(II or III) 3,5-di-tert-butylpyrazolates--the structures of. AB - The homoleptic rare-earth pyrazolate complexes [Sc(tBu2pz)3], [Ln2(tBu2pz)6] (Ln = La, Nd, Sm, Lu), [Eu4(tBu2pz)8] and the mixed oxidation state species [Yb2(tBu2pz)5] (tBu2pz = 3,5-di-tert-butylpyrazolate) have been prepared by a simple reaction between the corresponding rare-earth metal and 3,5-di-tert butylpyrazole, in the presence of mercury, at elevated temperatures. In addition, [Yb2(tBu2pz)6] was prepared by redox transmetallation/ligand exchange between ytterbium, diphenylmercury(II) and tBu2pzH in toluene, whilst the same reactants in toluene under different conditions or in diethyl ether gave [Yb2(tBu2pz)5]. The complexes of the trivalent lanthanoids display dimeric structures [Ln2(tBu2pz)6] (Ln = La, Nd, Yb, Lu) with chelating eta2-terminal and eta2:eta2 bridging pyrazolate coordination. The considerably smaller Sc3+ ion forms monomeric [Sc(tBu2pz)3] of putative D3h molecular symmetry, with pyrazolate ligands solely eta2-bonded. [Eu4(tBu2pz)8] is a structurally remarkable tetranuclear EuII complex with two types of europium centres in a linear array. The outer two are bonded to one terminal and two bridging pyrazolates, and the inner two are coordinated by four bridging ligands. Unprecedented mu-eta5:eta2 pyrazolate ligation is observed, with each outer Eu2+ sandwiched between two eta5 bonded pyrazolate groups, which are also eta2-linked to an inner Eu2+. The two inner Eu2+ ions are linked together by two equally occupied components of each of two symmetry related, disordered pyrazolate groups with one component eta4:eta2 bridging and one eta3:eta2 bridging. [La2(tBu2pz)6] has also been shown to be a Tishchenko reaction catalyst with several organic substrates. PMID- 11205005 TI - Spectroelectrochemical characterisation of poly[Ni(saltMe)]-modified electrodes. AB - Electrogenerated polymers based on the nickel(II) complex 2,3-dimethyl-N,N' bis(salicylidene)butane-2,3-diaminatonickel(II), poly[Ni(saltMe)], were characterised by in situ FTIR and UV/Vis spectroscopy and ex-situ EPR spectroscopy in order to gain insights into film structure, electronic states and charge conduction. The role of the nickel ions during film oxidation was probed by using EPR to study naturally abundant Ni and 61Ni-enriched polymers. The data from all the spectroscopic techniques are consistent, and clearly indicate that polymerisation and redox switching are associated with oxidative ligand based processes; coulometry suggests that one positive charge was delocalised through each monomer unit. EPR provided evidence for the non-direct involvement of the metal in polymer oxidation: the polymer is best described as a polyphenylene-type compound (conducting polymer), rather than an aggregation of nickel complexes (redox polymer), and the main charge carriers are identified as polarons. An explanation for the high electrochemical stability and conductivity of poly[Ni(saltMe)] with respect to that of poly[Ni(salen)] is proposed. based on stereochemical repulsion between monomeric units; this can impose a less compact supramolecular structure on polymers with bulkier substituents. PMID- 11205006 TI - The importance of dihydrogen complexes HnGe(H2)+ (n=0,1) to the chemistry of cationic germanium hydrides: advanced theoretical and mass spectrometric analysis. AB - Investigations of [Ge,Hn]-/0/- (n = 2,3) have been performed using a four-sector mass spectrometer. The results reveal that the complexes HnGe(H2)+ (n = 0,1) play an important role in the unimolecular dissociation of the metastable cations. Theoretical calculations support the experimental observations in most instances, and the established view that the global minimum of [Ge,H2]+ is an inserted structure may need reexamination; CCSD(T,full)/cc-pVTZ//CCSD(T)/6-311 ++ G(d,p) and B3LYP/cc-pVTZ studies of three low-lying cation states (2A1 HGeH+, 2B2 Ge(H2)+ and 2B1 Ge(H2)+) indicate a very small energy difference (ca. 4 kcal mol( 1)) between 2A1 HGeH+ and 2B2 Ge(H2)+; B3LYP favours the ion-molecule complex, whereas coupled-cluster calculations favour the inserted structure for the global minimum. Single-point multireference (MR) averaged coupled-pair functional and MR configuration interaction calculations give conflicting results regarding the global minimum. We also present theoretical evidence indicating that the orbital crossing point implicated in the spin-allowed metastable dissociation HGeH+* --> Ge(H2)+* --> Ge+ + H2 lies above the H-loss asymptote. Thus, a quantum-mechanical tunneling mechanism is invoked to explain the preponderance of the H2-loss signal for the metastable ion. PMID- 11205007 TI - Synthesis of enantiopure homoallylic ethers by reagent controlled facial selective allylation of chiral ketones. AB - The stereoselective allylation of chiral methyl ketones to give tertiary homoallylic ethers, which can easily be transformed into homoallylic alcohols, is described. Reaction of the enantiopure ketones 8a-d and the racemic ketones 26a-d with the norpseudoephedrine derivative 2 or ent-2 and allylsilane in the presence of a catalytic amount of trifluoromethanesulfonic acid, led to a series of homoallylic ethers with good to excellent diastereoselectivity (85:15 to > 97:3). The allylation is reagent controlled and nearly independent from the stereogenic centers in the substrates. A partial kinetic resolution was observed using the racemic ketones 26a-d. In the reaction of the chiral ketones 8a-d with the achiral reagents ethoxytrimethylsilane and allylsilane only a low diastereoselectivity was observed. PMID- 11205008 TI - The gas-phase reaction between hydroxide ion and methyl formate: a theoretical analysis of the energy surface and product distribution. AB - The potential energy surface for the prototype solvent-free ester hydrolysis reaction: OH- +HCOOCH3 --> products has been characterized by high level ab initio calculations of MP4/6-311 + G(2df,2p)//MP2/6-31 + G(d) quality. These calculations reveal that the approach of an OH- ion leads to the formation of two distinct ion-molecule complexes: 1) the MS1 species with the hydroxide ion hydrogen bonded to the methyl group of the ester, and 2) the MS4 moiety resulting from proton abstraction of the formyl hydrogen by the hydroxide ion and formation of a three-body complex of water, methoxide ion and carbon monoxide. The first complex reacts to generate formate anion and methanol products through the well known B(AC)2 and S(N)2 mechanisms. RRKM calculations predict that these pathways will occur with a relative contribution of 85% and 15% at 298.15 K, in excellent agreement with experimentally measured values of 87% and 13%, respectively. The second complex reacts by loss of carbon monoxide to yield the water-methoxide complex through a single minimum potential surface and is the preferred pathway in the gas-phase. This water-methoxide adduct can further dissociate if the reactants have excess energy. These results provide clear evidence that the preferred pathways for ester hydrolysis in solution are dictated by solvation of the hydroxide ion. PMID- 11205010 TI - Polycationic (mixed) core-shell dendrimers for binding and delivery of inorganic/organic substrates. AB - The convergent synthesis of a series of polycationic aryl ether dendrimers has been accomplished by a convenient procedure involving quantitative quaternarization of aryl(poly)amine core molecules. The series has been expanded to the preparation of the first polycationic, mixed core-shell dendrimer. All these dendrimers consist of an apolar core with a peripheral ionic layer which is surrounded by a less polar layer of dendritic wedges. These cationic, macromolecular species have been investigated for their ability to form assemblies with (anionic) guest molecules. The results obtained from UV/Vis and NMR spectroscopies, and MALDI-TOF-MS demonstrate that all the cationic sites throughout the dendrimer core are involved in ion pair formation with anionic guests giving predefined guest/host ratios up to 24. The large NMR spectroscopic shifts of resonances correlated with the groupings located in the core of the dendrimers, together with the relaxation time data indicate that the anionic guests are associated with the cationic core of these dendrimers. The X-ray molecular structure of the octacationic, tetra-arylsilane model derivative [Si(C6H3[CH2NMe3](2)-3,5)4]8+. 8I- shows that the iodide counterions are primarily located near the polycationic sphere. The new polycationic dendrimers have been investigated for their catalytic phase-transfer behavior and substrate delivery over a nanofiltration membrane. PMID- 11205009 TI - Comb-type cationic copolymer expedites DNA strand exchange while stabilizing DNA duplex. AB - The accelerating effect of cationic substances on the DNA strand exchange reaction between a 20 bp DNA duplex and its complementary single strand was studied. A polycationic comb-type copolymer, that consists of a poly(L-lysine) backbone and a dextran graft chain (PLL-g-Dex) and known to stabilize triplex DNA, expedites the strand exchange reaction under physiological relevant conditions. Electrostatically a small excess of the copolymer let to a 300-1500 fold increase in the DNA strand exchange while large excess of spermine or cetyltrimethylammonium bromide, a cationic detergent known to promote markedly hybridization of complementary DNA strands, shows only a slight effect. The efficacy of the copolymer was not affected by a 10 mM Mg2+ concentration. Notably the copolymer promotes the strand exchange reaction while it stabilizes double stranded DNA. The stabilization of strand exchange intermediates consisting of the parent duplex and the single strand by the copolymer is believed to be responsible for the observed acceleration behavior. PMID- 11205011 TI - The effect of pH on the reactions of catalytically important RhI complexes in aqueous solution: reaction of [RhCl(tppms)3] and trans-[RhCl(CO)(tppms)2] with hydrogen (TPPMS = mono-sulfonated triphenylphosphine). . AB - Hydrolysis and hydrogenation of [RhCl(tppms)3] (1) and trans-[RhCl(CO)(tppms)2] (2) was studied in aqueous solutions in a wide pH range (2 < pH < 11) in the presence of excess TPPMS (3-diphenylphosphinyl-benzenesulfonic acid sodium salt). In acidic solutions hydrogenation of 1 yields a mixture of cis-mer- and cis-fac [RhClH2(tppms)3] (3a,b) while in strongly basic solutions [RhH(H2O)(tppms)3] (4) is obtained, the midpoint of the equilibrium between these hydride species being at pH 8.2. The paper gives the first successful 1H and 31P NMR spectroscopic characterization of a water soluble rhodium(I)-monohydride (4) bearing only monodentate phosphine ligands. Hydrolysis of 2 is negligible below pH 9 and its hydrogenation results in formation of [Rh(CO)H(tppms)3] (5), which is an analogue to the well known and industrially used hydroformylation catalyst [Rh(CO)H(tppts)3] (6) (TPPTS = 3,3',3''-phosphinetriyltris(benzenesulfonic acid) trisodium salt). It was shown by pH-potentiometric measurements that formation of 5 is strongly pH dependent in the pH 5-9 range, this gives an explanation for the observed but previously unexplained pH dependence of several hydroformylation reactions. Conversely, the effect of pH on the rate of hydrogenation of maleic and fumaric acid catalyzed by 1 in the 2 < pH < 7 range can be adequately described by considering solely the changes in the ionization state of these substrates. All these results warrant the use of buffered (pH-controlled) solutions for aqueous organometallic catalysis. PMID- 11205012 TI - Hydrothermal synthesis, X-ray structure and complex magnetic behaviour of Ba4(C2O4)Cl2[[Fe(C2O4)(OH)]4]. AB - Hydrothermal reaction of iron(III) chloride, barium chloride and sodium oxalate in a narrow stoichiometry range produces the title compound Ba4(C2O4)Cl2[[Fe(C2O4)(OH)]4] (1). This new iron(II) oxalate crystallises in the tetragonal space group P42/mnm: a = 13.811(3), c = 7.026(2) A. The structure consists of parallel chains of mu2-hydroxy-bridged iron(II) ions. These are connected by bridging oxalates to form an anionic framework with large channels that contain the remaining barium, chloride and oxalate counter ions. Magnetisation studies on an oriented single crystal of 1 revealed a magnetic phase transition at 32 K and a strong easy-plane anisotropy at all temperatures. Above Tc the compound behaves as an S = 2XY antiferromagnetic chain, showing a broad maximum in the susceptibility at about 70 K. We determined the intrachain coupling J and the interchain coupling J' to be -7 cm(-1) and +0.4 cm(-1), respectively. The low-temperature phase is an ordered antiferromagnetic state. Zero- and longitudinal-field muon spin-rotation/relaxation studies support this interpretation; below Tc oscillations in the muon spin-autocorrelation function are observed giving unambiguous evidence for a non-zero sublattice magnetisation and proof of a long-range magnetically ordered state. PMID- 11205013 TI - Importance of packing coefficients of host cavities in the isomerization of open host frameworks: guest-size-dependent isomerization in cholic acid inclusion crystals with monosubstituted benzenes. AB - The crystal structures of inclusion compounds of cholic acid (CA) with 28 monosubstituted benzenes have been systematically investigated. All of the crystals belong to the monoclinic space group P2(1) and have bilayer structures with one-dimensional molecular channels that can include guest compounds. They are classified into four types of host frameworks that depend on the conformations and stacking modes of the host compound. The host frameworks and the host-guest ratios depend primarily on the molecular volumes of the guest compounds. The packing coefficient of the host cavity (PCcavity), which is the volume ratio of the guest compound to the host cavity, is used to clarify the relationship between the guest volume and isomerization of the host frameworks. The value of PCcavity, for stable inclusion compounds lies in the range of 55 70%. Compounds out of this range induce isomerization of the host frameworks. The packing coefficients of other host-guest compounds, in which the guest components are included in the host cavities through steric dimensions and van der Waals forces, are also in this range. These results indicate that PCcavity is a useful parameter correlation for guest recognition and isomerization of the host frameworks. PMID- 11205014 TI - X-H (X = C, N, O, P, S) bond activations induced by beta-heterosubstituted zirconaindenes. AB - The azazirconacyclopentene-substituted phosphines 3 and 4 have been found to activate the C-H bonds of acetylenic systems, such as methylpropiolate, diphenylphosphinoacetylene and phenylacetylene, or of methylene compounds, such as malonitrile and diethylmalonate, to give complexes 5a-c, 6a and 6b. C-H bond activation also takes place with vinylacetate. Similar reactions with amines, alcohols, enolisable ketones, phenols, phosphonates, thiols and a second generation SH-terminated dendrimer lead through X-H bond activation (X = N, O, P, S) to new complexes 8a-c, 9, 12 a,b, 13, 14a-c, 15, 16a and 16b. The azazirconacyclopentene-substituted amine 20 reacts to form analogous complexes. Zr-X bonds of these complexes (X = C, N, O, S) can be cleaved with diphenylchlorophosphine to give P-X phosphorus derivatives in high yield. PMID- 11205015 TI - Synthesis of clustered glycoside-antigen conjugates by two one-pot, orthogonal, chemoselective ligation reactions: scope and limitations. AB - Major histocompatibility class II antigens have been bound to clustered glycosides for selective targeting of the dendritic cell mannose receptor. Di-, tetra-, and octavalent glycoside-antigen conjugates have been obtained after two, orthogonal, hydrazone/thioether ligations, performed by using thio derivatives of D-mannose, D-galactose, or D(-)-quinic acid, glyoxylyl (or hydrazino)-N chloroacetylated lysinyl trees, and N-terminal hydrazino (or glyoxylyl) peptide antigens. Successful one-pot condensations have been developed to account for the nature of the antigens and the valency of the trees. PMID- 11205016 TI - Influence of topology on the long-range electron-transfer phenomenon. AB - Intramolecular electron-transfer phenomena in the radical anions derived from the partial reduction of diradicals (E,E)-p-divinylbenzene-beta,beta'-ylene bis(4 tetradecachlorotriphenylmethyl) diradical (1) and (E,E)-m-divinylbenzene beta,beta'-ylene bis(4-tetradecachlorotriphenylmethyl) diradical (2) have been studied by optical and ESR spectroscopy. The synthetic methodology used allows for complete control of the geometry of diradicals 1 and 2, which have para and meta topologies, respectively, as well as of their E/Z isomerism. This fact is used to show the influence of the different topologies on the ease of electron transfer, which is larger for the para than for the meta isomer, in which a small or negligible electronic coupling is observed. A related monoradical compound (E) bis(pentachlorophenyl)[4-(4-bromophenyl-beta-styryl)-2,3,5,6-tetrachlorophenyl] methyl radical (3), which has only one such redox site, has also been obtained and studied for comparison purposes. PMID- 11205017 TI - A potentiometric and 51V NMR study of the aqueous H+/H2VO4-/H2O2/L-alpha-alanyl-L histidine system. AB - The speciation in the quaternary aqueous H+/H2VO4-/H2O2/L-alpha-alanyl-L histidine (Ah) system has been determined from quantitative 51V NMR measurements and potentiometric data (glass electrode). The study was performed in 0.150 M Na(Cl) medium at 25 degrees C. Data were evaluated with the computer program LAKE, which is able to treat combined EMF and NMR data. The pKa values for Ah were determined as 8.06, 6.72 and 2.64. In the ternary H+/H2VO4-/Ah system, two complexes, (H+)p(H2VO4-)q(Ah)r, for which (p, q, r) values of (0, 1, 1) and (1, 1, 1) with log beta(0,1,1) = 2.52 +/- 0.03 and log beta(1,1,1) = 9.40 +/- 0.05 (pKa = 6.88), respectively, explain all data. The errors given are 3sigma. In the quaternary H+/H2VO4-/H2O2/Ah system, eight complexes were determined in addition to all binary and ternary complexes, four with a V/X/Ah ratio 1:1:1 and four with a ratio 1:2:1 (X = peroxo ligand). VX2Ah2- and VX2Ah- (pKa = 8.19) are the main complexes and predominate in the pH range 5 to 9. Three additional minor species have also been found but their compositions could not be determined owing to their small amounts. Equilibria are slow, significant decomposition of peroxide occurs only in acidic solutions. Data in the pH range 5 to 10 have been used for the LAKE calculations. Chemical shifts, compositions, and formation constants for the eight quaternary complexes are given, and equilibrium conditions are illustrated in distribution diagrams. Structural proposals for VX2Ah2- and VX2Ah- are made from 1H and 13C NMR measurements. PMID- 11205018 TI - Synthesis, characterisation, crystal structures, reactivity, and electrochemistry of ruthenium-nitrido, ruthenium-cobalt-imido and ruthenapyrrolidone carbonyl clusters containing alkyne ligands. AB - Thermolysis of [Ru3(CO)9(mu3-NOMe)(mu3-eta2-PhC2Ph)] (1) with two equivalents of [Cp*Co(CO)2] in THF afforded four new clusters, brown [Ru5(CO)8(mu-CO)3(eta5 C5Me5)(mu5-N)(mu4-eta2-PhC2Ph)] (2), green [Ru3Co2(CO)7(mu3-CO)(eta5-C5Me5)2(mu3 NH)[mu4-eta8-C6H4-C(H)C(Ph)]] (3), orange [Ru3(CO)7(mu-eta6-C5Me4CH2)[mu-eta3 PhC2(Ph)C(O)N(OMe)]] (4) and pale yellow [Ru2(CO)6[mu-eta3-PhC2(Ph)C(O)N(OMe)]] (5). Cluster 2 is a pentaruthenium mu5-nitrido complex, in which the five metal atoms are arranged in a novel "spiked" square-planar metal skeleton with a quadruply bridging alkyne ligand. The mu5-nitrido N atom exhibits an unusually low frequency chemical shift in its 15N NMR spectrum. Cluster 3 contains a triangular Ru2Co-imido moiety linked to a ruthenium-cobaltocene through the mu4 eta8-C6H4C(H)C(Ph) ligand. Clusters 4 and 5 are both metallapyrrolidone complexes, in which interaction of diphenylacetylene with CO and the NOMe nitrene moiety were observed. In 4, one methyl group of the Cp* ring is activated and interacts with a ruthenium atom. The "distorted" Ru3Co butterfly nitrido complex [Ru3Co(CO)5(eta5-C5Me5)(mu4-N)(mu3-eta2-PhC2Ph)(mu-I)2I] (6) was isolated from the reaction of 1 with [Cp*Co(CO)I2] heated under reflux in THF, in which a Ru-Ru wing edge is missing. Two bridging and one terminal iodides were found to be placed along the two Ru-Ru wing edges and at a hinge Ru atom, respectively. The redox properties of the selected compounds in this study were investigated by using cyclic voltammetry and controlled potential coulometry. 15N magnetic resonance spectroscopy studies were also performed on these clusters. PMID- 11205019 TI - The concept of docking and protecting groups in biohydroxylation. AB - The hydroxylation of unactivated carbon atoms employing methods developed in the realms of classical organic chemistry is difficult to achieve and the processes available lack the degree of chemo-, regio- and enantioselectivity required for organic synthesis. To improve this situation, the concept of docking/protecting groups should enable the organic chemist to employ biohydroxylation as an easy tool for preparative work. Similar to the common practice of using protective groups in organic chemistry, a docking/protecting (d/p) group is introduced first, then the biotransformation is performed, and finally the d/p group is removed. The aim of this concept is not only to avoid time consuming microorganism screening methods, but also to improve hydroxylation position predictability, prevent undesired side reactions, aid substrate detection, and product recovery. This approach is successfully applied to carboxylic acids, ketones, aldehydes, and alcohols. PMID- 11205020 TI - Synthesis and metal binding properties of salicylate-, catecholate-, and hydroxypyridinonate-functionalized dendrimers. AB - The synthesis, characterization, and metal-binding studies of chelate functionalized dendrimers is reported. Salicylate, catecholate, and hydroxypyridinonate bidentate chelators have been coupled to the surface of both poly(propyleneimine) (Astramol) and poly(amidoamine) (Starburst, PAMAM) dendrimers up to the fifth generation (64 endgroups). A general method has been developed for the facile and high quality chromatographic purification of poly(propyleneimine) and poly(amidoamine) dendrimer derivatives. One- and two dimensional (TOCSY) 1H NMR experiments and electrospray ionization mass spectrometry (ESI-MS) have confirmed the exhaustive coupling of these chelators to the primary amine functionalities of the dendrimers. Spectrophotometric titrations were used to investigate the metal binding ability of these macrochelates. Spectral analysis shows that ferric iron binding to these ligands is localized to the chelating endgroups. The ability of these dendritic polymers to bind large numbers of metal ions may lead to applications as metal sequestering agents for waste remediation technologies. PMID- 11205021 TI - Synthesis, structure, and magnetic properties of three new one-dimensional nickel(II) complexes: new magnetic model for the first one-dimensional S = 1 complex with alternating ferro-ferromagnetic coupling. AB - Three new one-dimensional nickel(II) complexes with the formulas trans-[Ni(N Eten)2(mu1.3-N3)]n(ClO4)n (1), trans-[Ni(N-Eten)2(mu1.3-N3)]n(PF6)n (2), and cis [Ni(N-Eten)(mu1.1-N3)2]n (3) (N-Eten = N-Ethylethylenediamine) were synthesized and characterized. Complex 1 has the P2(1)/c space group and consists of a structurally and magnetically alternating one-dimensional antiferromagnetic system with end-to-end azido bridges. Compound 2 has the P1 space group and has alternate units in its structure but consists of a magnetically uniform one dimensional antiferromagnetic system with end-to-end azido bridges. Complex 3 has the I2/a space group and may be described as a structurally and magnetically alternating one-dimensional ferromagnetic system with double azido bridged ligands in an end-on coordination mode. The chi(M)T versus T plots for compound 3 suggest an intramolecular ferromagnetic interaction between adjacent NiII ions and metamagnetism at low temperature (below 10 K). The magnetization measurements versus applied field confirm this metamagnetic ordering. In order to describe the magnetic data of this compound we developed a general formula for the magnetic susceptibility of the isotropic ferro-ferromagnetic S = 1 Heisenberg chain in terms of the alternation parameter alpha (= J2/J1); this assumed a variation of chi(M)T versus the length N. PMID- 11205022 TI - [DOTA-bis(amide)]lanthanide complexes: NMR evidence for differences in water molecule exchange rates for coordination isomers. AB - Two derivatives of 1,4,7,10-tetraazacyclododecane with trans-acetate and trans amide side-chain ligating groups have been prepared and their complexes with lanthanide cations examined by multinuclear NMR spectroscopy. These lanthanide complexes exist in aqueous solution as a mixture of slowly interconverting coordination isomers with 1H chemical shifts similar to those reported previously for the major (M) and minor (m) forms of the tetraacetate ([Ln(dota)]-) and tetraamide ([Ln(dtma)]3+) complexes. As in the [Ln(dota)]- and [Ln(dtma)]3+ complexes, the m/M ratio proved to be a sensitive function of lanthanide size and temperature. An analysis of 1H hyperfine shifts in spectra of the Yb3+ complexes revealed significant differences between the axial (D1) and non-axial (D2) components of the magnetic susceptibility tensor anisotropy in the m and M coordination isomers and the energetics of ring inversion and m <==> M isomerization as determined by two-dimensional exchange spectroscopy (EXSY). (17)O shift data for the Dy3+ complexes showed that both have one inner-sphere water molecule. A temperature-dependent (17)O NMR study of bulk water linewidths for solutions of the Gd3+ complexes provided direct evidence for differences in water exchange rates for the two coordination isomers. The bound-water lifetimes (tauM298) in the M and m isomers of the Gd3+ complexes ranged from 1.4-2.4 micros and 3-14 ns, respectively. This indicates that 1) the inner-sphere water lifetimes for the complexes with a single positive charge reported here are considerably shorter for both coordination isomers than the corresponding values for the [Gd(dtma)]3+ complex with three positive charges, and 2) the difference in water lifetimes for M and m isomers in these two series is magnified in the [Gd[dota-bis(amide)]] complexes. This feature highlights the remarkable role of both charge and molecular geometry in determining the exchange rate of the coordinated water. PMID- 11205023 TI - Mild and efficient flavin-catalyzed H2O2 oxidations. AB - Based on a previously discovered method for amine oxidations using flavins as catalysts and hydrogen peroxide as oxidant, a comparative kinetic study using NMR spectroscopy was undertaken with a series of flavins for amine and thioether oxidations. Included in this series is the newly prepared 7,8-difluoro-1,3 dimethyl-5-ethyl-5,10-dihydroalloxazine. This study shows that flavins, which bear electron-donating groups on the aromatic ring and/or the N-10 position, are less active and are deactivated during the course of the reaction. Moreover, flavins that are alkylated at the N-1 position instead of the N-10 position and having either no substituents or electron-withdrawing groups on the aromatic ring, remain the most active and stable. PMID- 11205024 TI - Self-assembly and selective guest binding of three-dimensional open-framework solids from a macrocyclic complex as a trifunctional metal building block. AB - The nickel(II) hexaazamacrocyclic complex (1) containing pendant pyridine groups has been synthesized by the one-pot template condensation reaction of amine and formaldehyde. From the self-assembly of 1 with deprotonated cis,cis-1,3,5 cyclohexanetricarboxylic acid, H2CTC- and CTC3-, three-dimensional supramolecular open-frameworks of [Ni(C20H32N8)][C6H9(COOH)2(COO)]2 x 4H2O (2) and [Ni(C20H32N8)]3[C6H9(COO)3]2 x 16H2O (3), respectively, have been constructed. The solids 2 and 3 are insoluble in all solvents. X-ray crystal structure of 2 indicates that each nickel(II) macrocyclic complex binds two H2CTC- ions in trans position and two pendant pyridine groups of the macrocyclic complex are involved in hydrogen-bonding interactions with the hydroxy groups of H2CTC- belonging to the neighboring macrocyclic complexes, which provides the beltlike one dimensional chain composed of rectangular synthons. The one-dimensional chains are linked together through lattice water molecules by the hydrogen-bonding interactions to generate two-dimensional networks, which are again connected to each other by the offset pi-pi stacking interactions between the pendant pyridine rings to give rise to a three-dimensional structure in which channels are present. The X-ray crystal structure of 3 indicates that each nickel(II) macrocyclic unit binds two CTC3- ions in trans position and each CTC3- ion coordinates three nickel(II) macrocyclic complexes to form a two-dimensional layer, in which pendant pyridine rings are involved in the hydrogen bonding and the herringbone pi-pi interaction. Between the layers, the pendant pyridine rings belonging to the neighboring layers participate in the offset pi-pi stacking interactions, which gives rise to a three-dimensional network structure. The network creates channels running parallel to the a, b, and c axes, which are filled with guest water molecules. The X-ray powder diffraction patterns indicate that the frameworks of 2 and 3 are deformed upon removal of water guests but restored upon rebinding of water. The host solids 2 and 3 bind [Cu(NH3)4](ClO4)2 in MeCN with a binding constant (Kf) of 210 M(-1) and 710 M(-1), respectively, while they do not bind [Cu(en)2](ClO4)2 (en = ethylenediamine). The dried solids of 2 and 3 do not interact with benzene and toluene, but they differentiate methanol, ethanol, and phenol in toluene solvent with the Kf values of 42, 14, and 12 M(-1), respectively, for 2, and 13, 8.2, and 8.9 M(-1), respectively, for 3. In terms of binding sites for guest molecules, the solid 3 has greater capacity than the solid 2. PMID- 11205025 TI - Hydraphile channels: models for transmembrane, cation-conducting transporters. AB - A completely synthetic, non-peptide channel has been prepared and shown to conduct cations across a phospholipid bilayer membrane. Studies have been undertaken to assess the compound's location within the bilayer and to better understand its function. These studies are described along with background on the design and concept of the channel. PMID- 11205026 TI - Discovery through total synthesis: a retrospective on the himastatin problem. AB - A total synthesis of a structure proposed for himastatin was accomplished. The non-identity of the fully synthetic material with himastatin necessitated a revision of the assigned structure. Confirmation of the revised stereostructure was subsequently confirmed through total synthesis. Among the achievements during this effort were i) stereospecific routes to both anti-cis and syn-cis pyrrolindoline substructures; ii) a practical synthesis to 5-hydroxypiperazic acid in enantiomerically pure form; iii) a Stille coupling leading to a complex bi-indole moiety, and iv) efficient protecting group management throughout the evolving depsipeptide domain. The outlines for a biological pharmacophore have been delineated. The alternating D- and L-substituents in the 6-mer as well as the biaryl linkage connecting the two identical subunits are critical for maintaining biological activity. This pattern is simulated in another antibiotic, and suggests a possible structural trend for future SAR investigations. PMID- 11205027 TI - Inulin as a carrier for contrast agents in magnetic resonance imaging. AB - Magnetic resonance angiography (MRA) has put forth an impetus for the development of macromolecular GdIII complexes that have a prolonged lifetime in the vascular system. Herein, we report the synthesis and GdIII complexation of a new sugar conjugate based on inulin and the DO3A ligand (DO3A = 1,4,7,10 tetraazacyclododecan-1,4,7-triacetic acid). Two API-DO3ASQ conjugates (API = O (aminopropyl)inulin, SQ = squaric acid = 3,4-dihydroxy-3-cyclobutene-1,2-dione) with different degrees of substitution (ds = 0.7 and ds = 1.5) were prepared from API by using the diethyl ester of squaric acid as a linking agent for the DO3A chelate. The efficacies of the resulting GdIII compounds were evaluated by investigation of their water 1H longitudinal-relaxation-rate enhancements at variable field (NMRD). A dramatic increase in relaxivity was observed in the more highly substituted conjugate (ds = 1.5); this prompted us to do a variable temperature (17)O study in order to further characterize the relaxation parameters involved in this system. [Gd(API-DO3ASQ)] shows promising properties for application as a contrast agent for MRI. PMID- 11205028 TI - Towards a correlation of absolute configuration and chiroptical properties of alkyl aryl sulfoxides: a coupled-oscillator foundation of the empirical Mislow rule? AB - The absorption and circular dichroism (CD) data for a series of alkyl aryl sulfoxides 1-16 of known S configuration have been analyzed. The strong bathochromic effect exerted by the nitro group in the para position of the phenyl sulfoxides indicates that the sulfur atom acts as an electron donor moiety towards the phenyl ring. Such behavior requires a significant 2p(C)-3sp3(S) overlap, and therefore the phenyl (and p-substituted phenyl) sulfoxides 1-12, as well as the 2-naphthyl sulfoxides 15 and 16, must assume a conformation which permits such orbital overlap. The steric effect of the peri hydrogen in 1 naphthyl-substituted compounds 13 and 14 does not allow a conformation of this type, and in these compounds the above-mentioned 2p(C) and 3sp3(S) orbitals are positioned in almost orthogonal planes. This conformational difference is clearly shown by the absorption spectra: compounds 1-12, 15, and 16 show the lowest energy sigma --> sigma* transition of the sulfoxide chromophore at approximately 250 nm, indicating the existence of a conjugated S=O chromophore. In contrast, the corresponding absorption in 13 and 14 occurs at about 200 nm, indicating the presence of an isolated S=O chromophore. The CD spectra of 13 and 14 show a negative, couplet-like feature between 250 and 200 nm. This spectral feature can be interpreted in terms of exciton coupling between the allowed sigma --> sigma* transition of the isolated S=O chromophore at 200 nm and the 1B transition of the naphthalene chromophore. In fact, the Harada-Nakanishi rule predicts a negative CD couplet for an S-configured sulfoxide in the conformation found by UV analysis, as found experimentally. The CD spectrum of 13 is quantitatively reproduced by DeVoe coupled-oscillator calculations, strongly implying that a coupled-oscillator mechanism is operative in determining the optical activity of 13 and 14. This approach has also tentatively been extended to the conjugated sulfoxides 1-12, taking into account the coupling of the benzene chromophore 1La transition with the sigma --> sigma* transition of the S=O chromophore. In this case the Harada-Nakanishi rule also predicts a negative CD couplet for the S configured sulfoxides, as found experimentally. PMID- 11205029 TI - Synthesis of the enantiomers of 6-deoxy-myo-inositol 1,3,4,5-tetrakisphosphate, structural analogues of myo-inositol 1,3,4,5-tetrakisphosphate. AB - D-myo-Inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4] is produced rapidly from the established second messenger D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P4] in stimulated cells. Despite extensive investigations, in particular concerning its potential role in mediating cellular Ca2+ influx, no exact cellular function has been described for this inositol phosphate; however, binding sites have been identified in a number of tissues and it has been shown to act synergistically with Ins(1,4,5)P3. To assist in the elucidation of the mechanism of action and structural requirements within the Ins(1,3,4,5)P4 moiety that are necessary for recognition and activation of the receptor, structural analogues of this tetrakisphosphate are required. Routes for the synthesis of racemic 6-deoxy-myo-inositol 1,3,4,5-tetrakisphosphate [6-deoxy-DL Ins(1,3,4,5)P4] and the chiral antipodes D- and L-6-deoxy-myo-inositol 1,3,4,5 tetrakisphosphate are described here. The racemic tetrakisphosphate was synthesised from DL-1,2-O-isopropylidene-myo-inositol in eight steps. Deoxygenation at C-6 was achieved following the Barton-McCombie procedure. Both chiral tetrakisphosphates were synthesised through resolution of racemic cis-diol 6-deoxy-1,4,5-tri-O-p-methoxybenzyl-myo-inositol with the chiral auxiliary (S) (+)-O-acetylmandelic acid. Absolute configuration was confirmed by synthesis of the known D-6-deoxy-myo-inositol. Both D-6-deoxy-Ins(1,3,4,5)P4 and its enantiomer will be useful tools to unravel the enigmatic role of Ins(1,3,4,5)P4 in the polyphosphoinositide pathway of signal transduction. PMID- 11205030 TI - Supramolecular detection of metal ion binding: ligand conformational control of cholesteric induction in nematic liquid crystalline phases. AB - Tripodal tetradentate ligands may act as chemosensor molecules. Their ability to torque a nematic into a cholesteric phase increases upon complexation with copper ion. Moreover, changes in overall shape of the complexes induced by different metals and counter ions were transferred sensitively to the supramolecular level, observed by proportionate changes in the degree of twisting. Modification of the oxidation state of the metal center also gave large changes in twisting power; this suggests potential application in electrochemical molecular switches. The handedness of the induced cholesteric phase is related to the stereochemistry of the ligand: The small amount of chiral dopant needed for the LC technique (less than 2 nmol) suggests the possible determination of the absolute configuration of the parent primary amines of the ligands. PMID- 11205031 TI - Aza-[3,3]-Claisen enolate rearrangement in vinylaziridines: stereoselective synthesis of mono-, di-, and trisubstituted seven-membered lactams. AB - Several 2,3-disubstituted vinylaziridines have been N-acylated and subjected to LiHMDS in THF at -78 degrees C. Upon warming to room temperature, the resulting amide enolates underwent a highly stereoselective [3,3]-sigmatropic rearrangement to give mono-, di-, and trisubstituted seven-membered lactams in good yields. The scope and limitations of the process have been investigated by using variously substituted vinylaziridines. A kinetically controlled process proceeding through a six-membered boatlike transition state assembly has been invoked to explain the stereochemical outcome of the reaction. PMID- 11205032 TI - Synthesis, mesomorphism, and unusual magnetic behaviour of lanthanide complexes with perfluorinated counterions. AB - Lanthanide complexes of the Schiff base ligand 4-dodecyloxy-N-hexadecyl-2 hydroxybenzaldimine and with perfluorinated alkyl sulfate counterions were synthesised. All of the metal complexes show a smectic A mesophase. The viscosity of this mesophase is much lower than that of analogous compounds with nitrate or alkyl sulfate counterions. The behaviour of these new highly anisotropic molecular magnetic materials was studied using high-temperature X-ray measurements in an external magnetic field and temperature-dependent magnetic susceptibility measurements. The mu(eff)-versus-temperature curve is more comparable with those expected for nematic phases than for smectic phases. The luminescence spectrum of a EuIII compound shows that the values of the second rank crystal field parameters are very large. The huge magnetic anisotropy can be related to this strong crystal-field perturbation. PMID- 11205033 TI - [Cajal and neuroscience in the eve of the third millenium]. AB - This is a brief history of the birth of Neuroscience as an independent branch of knowledge. The importance of Cajal's contribution to the structuralization of modern Neuroscience is described. Outstanding contributions to Neuroscience of the last century, particularly the Decade of the Brain, are summarized. The reason for the huge increase and interest in neuroscientific studies are given. Finally, I emphasize the challenge that multidisciplinary study and interinstitutional collaboration pose to advancing our knowledge of the human brain. The second part of the talk demonstrated the validity of Cajal's work in modern Neuroscience insisting on three aspects: 1) the microscopic study of the Mammalian central nervous system, 2) the neurogenesis and development of the nervous system and 3) the degeneration, regeneration and plasticity of the central nervous system. I conclude that Cajal's timeliness is reflected by the fact that there are few problems in modern Neuroscience which Cajal did not address at one time or other. PMID- 11205034 TI - [Prognostic value of optic morphometry in colorectal cancer]. AB - In many types of cancer, certain morphometric characteristic of tumor cells correlate with patient survival. Our observations suggested that the survival of patients with colorectal carcinomas is negatively correlated with tumor-cell nucleus size. METHODS: We investigated relationships between postsurgery survival and nucleus morphometric in 90 patients who had undergone resection for a colorectal tumor. The nucleus-size variables considered were maximum diameter, minimum diameter, perimeter, area, and form factor (means for 100 nuclei from each patient were used in all cases). RESULTS: Our results confirmed that patients with large maximum nucleus diameter (where large = greater than the first quartile) have significantly worse survival than patients with smaller maximum nucleus diameter (mean survival, 28 vs. 43 months). Similar results were obtained for the other nucleus-size variables. Stepwise Cox regression analysis was then performed, with postsurgery survival time as the dependent variable and the following candidate independent variables: age, gender. Dukes class, degree of histologic differentiation, the various nucleus-size variables, and relative frequencies of different nucleus shapes (spherical, oval, cylindrical, fusiform, and irregular). The variables selected for the prognostic model were Dukes class, relative frequency of irregular nuclei, and maximum nucleus diameter. CONCLUSIONS: These findings indicated that nucleus size and shape are useful predictors of survival. Even in Dukes class is known, consideration of nucleus size and shape significantly improves prediction of survival. PMID- 11205035 TI - [Criteria for the extension of gastric and lymphatic resection in gastric cancer surgery]. AB - After a brief historical review where are pointed out the circuMstances of the first successful gastrectomy performed by Billroth (Billroth I), gastroenteroanastomosis by Wolfler, Wolfler and Roux in-Y anastomosis, Billroth II reconstruction and types and techniques of lymphadenectomies, it is exposed the author's experience over 927 gastric cancer, cardias included, explaining the surgical technique performed: gastrectomy according to size, tumor localization and D1 lymphadectomy, evaluating to perform a D2 during operation, obtaining an overlife of 56% after 5 years when tumor was only placed in the stomach, and only of 19% when N1 lymph-nodes where affected and 6% if invasion reached N2 group. Overlife of cardias cancer has moved between 11 and 20%. Some comments are made on the surgeon evaluation of the lymp-nodes afectation and on the advantages and disadvantages of performing a radical or standard lymphadenectomy. PMID- 11205037 TI - [Decision making: biological bases and limitations]. AB - In the human brain, simple molecules and complex circuits are constantly making decisions which are indispensable for our survival and also to accomplish a variety of daily activities such as walking, memorizing, conversing, composing music, painting or poetry.... All are the result of the integration of many neural systems that perceive many and simultaneous visual, tactile, auditory and/or mental stimuli. Once synthetized, they are immediately transmitted to the corresponding executive systems, thus completing the fascinating functional loop of decision-making: a) perception of stimuli or information which originate in the environment, b) selection and elaboration of the decision which is considered more appropriate or attractive according to personal experience or intuition and c) execution. If these neural nets have been damaged or haven failed to develop the mechanisms of facilitation or inhibition that govern them become unbalanced. If inhibition is reduced, excessive and violent behaviour is expressed as in patients suffering from manic phases. Conversely, if inhibition is excessive, decision making mechanisms are not operative. In either case, behaviour is not "reasonable" and does not follow prototypical patterns. All these processes must be the consequence of a constant molecular activity full of micro-decisions whose effectiveness depends on the histological and biochemical integrity of the neurons. This microenvironment is responsible for all types of decisions of all forms of life and represents one of the fundamental successes of evolution. PMID- 11205036 TI - [New concepts on atrial fibrillation]. AB - Atrial Fibrillation (AF) is the most common sustained arrhythmia in humans. AF has a self-perpetuating nature. Perpetuation has been attributed to shortening of atrial action potential duration (APD) and APD adaptation to rate, the so called atrial electrical remodeling. There is evidence that alterations in gene expression of proteins involved in the Ca handling may be, at least partly, responsible for AF-induced electrical remodeling. This review focus on the possible cellular mechanisms involved in atrial remodeling, followed by a brief description of new therapeutic approaches that target the development of the arrhythmogenic substrate, rather than simply attacking the final electrophysiologic environment. PMID- 11205038 TI - [The myth of "tabula rasa"]. AB - The history of the philosophy has witnessed a controversy between those who maintain that the human being is born with inherited knowledge and those who assert that the mind of man is like a "tabula rasa", a tablet on which nothing has been written. Recent experiments have shown that the last group was wrong. The human being is born endowed with certain types of knowledge which were already present in those animals which preceded us in the evolution. The fear of snakes, the number sense and the recognition of familiar faces are three typical examples among others. PMID- 11205039 TI - [Estrogens and breast cancer]. AB - After a short bibliographical revision on the estrogen action in the genesis of mammarian cancer, it can be accepted that they can only act under the analyzed circumstances. For these reasons, it is advised that the Substitutive Hormonal Therapy (SHT) during menopause with estrogens should not be extended for more than five years, nor should it be given to women over 60 years of age. SHT combined with progesterone protects against endometrial cancer, but increases the relative risk of mammarian cancer. It should not be prescribed for hysterectomized patients who should follow previous advices. Both types of SHT should be avoided by hypertensive women treated with calcium blockers and women have familiar records of mamarian cancer. PMID- 11205041 TI - [Historical and clinical aspects of prolonged pregnancy]. AB - The author analyses the subject of prolonged pregnancy from two perspectives. Firstly, the current Clinical view, and secondly, looking far back into the past, a perspective which offers historical considerations. The Medical and Legal aspects of the matter are approached historically (130 B.C., Alfonso el Sabio). The French, English, and Spanish jurisprudence is approached from the perspective of the 20th century. Pregnancy duration is analysed in the human species as well as in various other animal species. Other factors also taken into account include the start of the birth process, seen from the viewpoint of the sixties up to the current neuro-endocrine knowledge. The author concludes by presenting a synopsis of the current means available for precisely determining the true length of pregnancy. PMID- 11205042 TI - [Potential therapeutic usefulness of cannabis and cannabinoids]. AB - Diseases in which Cannabis and cannabinoids have demonstrated some medicinal putative properties are: nausea and vomiting associated with cancer chemotherapy, muscle spasticity (multiple sclerosis, movement disorders), pain, anorexia, epilepsy, glaucoma, bronchial asthma, neuroegenerative diseases, cancer, etc. Although some of the current data comes from clinical controlled essays, the majority are based on anecdotic reports. Basic pharmacokinetic and pharmacodynamic studies and more extensive controlled clinical essays with higher number of patients and long term studies are necessary to consider these compounds useful since a therapeutical point of view. PMID- 11205043 TI - [Pediatric problems of the children of immigrants in Spain]. AB - The author, Consultant and Expert in Maternal and Child Health of the WHO in Africa and Europe, after a complete study of the Spanish demography, the country with the lower natality in all the world, arrives to the conclusion that Spain is the country with more possibilities for the immigration from Africa, Latino America and Philippines. So, is absolutely necessary that Spanish paediatricians know the troubles and diseases of the children of these groups as a way for their integration. PMID- 11205044 TI - [Evidence-based nuclear medicine and experience-based nuclear medicine]. AB - The basis and methods of Evidence-Based medicine (EBM) and its applications in Nuclear Medicine (NM) are described. EBM criteria are contrasted with clinical experience. Some NM Meta-analysis and Systematic Reviews are described. The methods of redefining the probability through diagnostic tests and the methods of Decision Analysis and of Cost-Efficiency Studies applied to NM are described. Finally a Series of proposals to improve the application of EBM to NM are presented. PMID- 11205045 TI - [The problem of truth in psychiatry]. AB - Psychiatry has forgotten too early about the problem of truth (Zutt). In the first treatises on delusions, these are described as pathological errors, as mistakes in the ability to judge reality. For French psychiatry, delusions are false ideas of pathological origin, resistant to logical argumentation that alter the ability to judge reality, a concept still present in DSM-IV, in which it is defined as wrong beliefs that normality imply a wrong interpretation of perceptions of experiences. As a consequence, delusions are classified according to its contents. German psychiatry however seeks for the structures underlying to all delusions, some authors have even defended the notion of a single psychosis. The Heidelberg School, so well analyzed by Lain, developed a psychopathology which dismantled the notion of delusion then accepted (falseness is a relative and accessory notion and the lack of information plays an important role, as well as cultural and religious factors). K. Schneider describes the two forms of delusion: delusional perception and delusional occurrence. Both concepts have been criticized, therefore it is necessary to consider truth as a process and not as a state and to take into account the contributions of the philosophy of science and psychoanalysis. The concept of truth of Aristotle (the adaptation of the logos to the thing) is the one that has prevailed along history. But, for Heidegger the truth as aletheia (the process of revealing) is deeper and allows, applied to psychopathology, the connection of truth, liberty and relationship between human beings. As a consequence, the error of delusion, its lack of liberty, is also a lack of communication. The process of getting closer to truth is marked by an ethical attitude of tolerance. PMID- 11205046 TI - Intracellular regulation of inward rectifier K+ channels. AB - Inward rectifier potassium (Kir) channels comprise a relatively young gene family of ion channels whose first member was isolated in 1993. A common property its members share is a strong dependence on intracellular regulators such as polyamines, nucleotides, phospholipids, kinases, pH and guanosine-triphosphate binding proteins (G-proteins). The physiological role of Kir channels is to modulate the excitability and secretion of potassium (K+) to maintain K+ homeostasis, under the control of various intracellular second messengers. Structurally, Kir channels are assembled from four alpha-subunits each carrying the prototypic K+-channel pore region lined by two transmembrane segments with intracellular N- and C-termini. The exact molecular mechanism of Kir channel gating by intracellular second messengers is of considerable biophysical interest. Recent studies have gained significant insight into the molecular mechanism of intracellular regulation by pH. This review illustrates the various modes of regulation of this class of ion channel and the present knowledge of the underlying molecular mechanisms. PMID- 11205047 TI - Restoration of cardiac transient outward potassium current by norepinephrine in diabetic rats. AB - In cardiac ventricle, the density of the transient outward potassium current, Ito, is clearly related to sympathetic nervous system integrity. This sympathetic regulation of Ito expression may be greatly significant to the genesis of cardiac complications of several diseases such us diabetes mellitus. Autonomic neuropathy, including cardiac neuropathy, is a complication of chronic diabetes. The objective of the present study was to identify the possible role of cardiac sympathetic neuropathy in the reduction of Ito current density in diabetic ventricular myocardium. Thus, we employed the patch-clamp technique to test whether Ito can be restored in diabetic myocytes incubated with norepinephrine. We also measured, using HPLC, the catecholamine content of the stellate ganglion, which is responsible for cardiac sympathetic innervation, in normal and diabetic animals. The main result of the present study was to show that a 24-h incubation of diabetic cells with norepinephrine restores Ito density to control values. The restoration of Ito current density by norepinephrine suggests that the diabetes induced reduction of Ito is at least partially attributable to a reduced trophic effect of norepinephrine on the expression of Ito. PMID- 11205048 TI - Rapid cooling-induced contractures in rat skinned skeletal muscle fibres originate from sarcoplasmic reticulum Ca2+ release through ryanodine and inositol trisphosphate receptors. AB - Previous reports have shown that cooling striated muscles induces contractile responses that are related to Ca2+ release from the sarcoplasmic reticulum. However, the effect of cooling has generally been studied in the presence of pharmacological agents that potentiate rapid cooling-induced contractures. The present study shows that in saponin-skinned rat skeletal muscle preparations, a drop in temperature from 22 degrees C to 2 degrees C per se induces a contracture which relaxes on return to 22 degrees C. In fast-twitch fibres, rapid cooling induced contractures are fully blocked by ryanodine, an inhibitor of ryanodine receptors. By contrast, in slow-twitch fibres, ryanodine partially inhibits the rapid cooling-induced contractile response, leaving a residual tension that dissipates after application of inositol 1,4,5-trisphosphate (InsP3). At low concentrations, heparin, an inhibitor of InsP3 receptors, decreases rapid cooling induced contractures in both types of muscle. The present results suggest that in skeletal muscle, rapid cooling-induced contractures are due to both ryanodine sensitive and InsP3-sensitive Ca2+ release from the sarcoplasmic reticulum. PMID- 11205049 TI - pH regulation in isolated in vitro perfused rat colonic crypts. AB - We investigated disorders and regulation of cytosolic pH (pHi) in isolated perfused crypts from rat distal colon using the pH-sensitive dye BCECF. This preparation allows distinct examination of either luminal or basolateral transport. The effects of luminal weak organic acids and bases on pHi were examined. The physiological concentrations of both luminal CO2/HCO3- and acetic acid/acetate acidified pHi significantly, but less than when applied from the basolateral side. Corresponding changes (luminal versus basolateral) in pHi were 0.17+/-0.04 versus -0.39+/-0.04, (n=8) and -0.15+/-0.02 versus -0.41+/-0.04, (n=8), respectively. Basolateral versus luminal application of NH3/NH4+ led to a more marked change in pHi, namely 0.35+/-0.03 versus 0.008+/-0.007 pH units, (n=19). The luminal perfusion of NH3/NH4+ was controlled by applying fura-2 acid to the luminal side and at the same time recording fura-2-specific fluorescence. Hence, the influence of luminal acid/base on colonic pHi homeostasis was limited. To examine pHi regulation, we investigated the recovery from an intracellular acid load using the NH3/NH4+ pulse method. Recovery was completely dependent on basolateral Na+, indicating that luminal acid/base transport does not play a major role in pHi homeostasis. The basolateral transporters involved in pHi recovery are probably the EIPA- and HOE694-inhibitable (IC50=0.2 and 2 micromol/l, respectively) Na+/H+ exchanger NHE1 and the DIDS-inhibitable Na+ dependent HCO3- importer. PMID- 11205050 TI - Osmolyte and Na+ transport balances of rat hepatocytes as a function of hypertonic stress. AB - The initial event in the regulatory volume increase (RVI) of rat hepatocytes is an influx of Na+ that is then exchanged for K+ via stimulation of Na+/K+ adenosine triphosphatase (ATPase). In this study, we analysed the activation pattern of the Na+ transporters underlying RVI as a function of the degree of hypertonic stress. In confluent primary cultures, four hypertonic conditions were tested (changes from 300 to 327, 360, 400 or 450 mosmol/l) and the activities of Na+ conductance, Na+/H+ antiport, Na+-K+-2Cl- symport and Na+/K+-ATPase were quantified using intracellular microelectrodes, microfluorometry and time dependent, furosemide- or ouabain-sensitive 86Rb+ uptake, respectively. Neither Na+ conductance nor Na+-K+-2Cl- symport responded to 327 mosmol/A. At 360, 400 and 450 mosmol/l, uptake via these transporters would lead to increases of cell Na+ by 33.0, 49.0 and 49.0 and by 4.5, 10.4 and 9.2 mmol/l per 10 min, respectively. In contrast, Na+/H+ antiport exhibited 65% of its maximal activation already at 327 mosmol/l. At the four osmolarities tested, this transporter would augment cell Na+ by 6.9, 8.9, 9.8 and 10.6 mmol/l per 10 min. The sums of Na+ import were consistent with the amounts of Na+ exported via Na+/K+-ATPase plus the actual increases of cell Na+ (21.2, 58.5, 63.6 and 68.3 mmol/l per 10 min and 2.2, 4.0, 6.3 and 8.2 mmol/l, respectively). In addition, these elevations of cell Na+ plus the increases of cell K+ (via Na+/K+-ATPase) that amounted to 5.0, 6.5, 17.5 and 18.4 mmol/l were consistent with the increases of intracellular osmotic (cationic) activity of 2.5, 11.5, 21.0 and 28.5 mmol/l, respectively, computed from RVI data. It is concluded that the principle of rat hepatocyte RVI, i.e. an initial uptake of Na+ that is then exchanged for K+ via Na+/K+-ATPase, is realized over the entire range of 9-50% hypertonicity tested. The set-point for the activation of RVI clearly lies below 327 mosmol/l. Na+/H+ antiport is the most sensitive Na+ importer involved in RVI, whereas Na+ conductance plays the prominent role from 360 mosmol/l upwards. PMID- 11205051 TI - Voltage-driven p-aminohippurate, chloride, and urate transport in porcine renal brush-border membrane vesicles. AB - p-Aminohippurate (PAH) and urate are secreted into the proximal tubule lumen across the brush-border membrane. Here we used brush-border membrane vesicles from pig kidney to study PAH and urate transport. Efflux and influx of [3H]PAH were influenced by K+-diffusion potentials indicating electrogenic PAH transport. An outside>inside PAH concentration difference accelerated voltage-sensitive, Na+ coupled D-glucose uptake as efficiently as did an outside>inside Cl- concentration difference, suggesting comparable conductances for PAH and Cl- in brush-border membrane vesicles. Up to 1 mM of the uricosurics indacrinone, tienilic acid, losartan and probenecid, as well as of the stilbenes, DIDS and SITS, and of the loop diuretics furosemide and bumetanide inhibited voltage driven PAH uptake, but not, or only slightly, voltage-driven Cl- uptake. Voltage driven [14C]urate uptake, however, was inhibited by 0.1 mM DIDS, 0.2 mM losartan and 0.5 mM probenecid to a similar extent as [3H]PAH uptake. One millimolar pyrazinoic acid, oxonate, xanthine and adenosine inhibited neither [3H]PAH nor [14C]urate uptake. These results suggest that PAH and urate share an anion conductance which is distinct from the Cl- conductance and is probably not the same as a recently identified urate channel (Leal-Pinto E et a]. J Biol Chem 272:617-625, 1997). PMID- 11205052 TI - Nitric oxide has no beneficial effects on ion transport defects in cystic fibrosis human nasal epithelium. AB - Nitric oxide (NO) has been reported to activate Cl- secretion via the cystic fibrosis transmembrane conductance regulator (CFTR) and inhibit epithelial Na+ absorption mediated by amiloride-sensitive epithelial Na+ channels (ENaC). These ion transport systems are defective in cystic fibrosis (CF): Cl- secretion by CFTR is impaired and Na+ absorption by ENaC is dramatically increased. By activating CFTR and depressing ENaC, NO is a potentially beneficial therapeutic agent for ion transport defects in human CF respiratory epithelia. To assess the effects of NO on human respiratory epithelial cells, the NO donors sodium nitroprusside (SNP) and spermine NONOate were applied to primary cultured nasal cells, surgically obtained from non-CF and CF patients. Measurements of transepithelial short-circuit current (ISC) showed that NO has no inhibitory potency against amiloride-sensitive nasal ENaC (nENaC) or amiloride-insensitive Na+-absorbing mechanisms in non-CF and CF epithelia. Furthermore, NO had no stimulatory effect on Cl- secretion by CFTR or any other Cl- conductance pathway in either tissue. Although NO elevated the intracellular Ca2+ concentration, we did not detect any activation of Ca2+-dependent Cl- channels. These results demonstrate that NO has no beneficial effect on CF epithelial cells of the upper airways. PMID- 11205053 TI - Calcitonin gene-related peptide suppresses the transient outward current in rat ventricular myocytes. AB - The effects of calcitonin gene-related peptide (CGRP) on the transient outward current (Ito) and the L-type calcium current (ICa,L) were investigated in isolated rat ventricular cardiomyocytes using the whole-cell, patch-clamp technique. CGRP influenced neither the amplitude nor the time course of ICa,L. On the other hand, at all membrane potentials at which a significant Ito was elicited, CGRP decreased its amplitude. The effect on Ito was completely reversible and independent of membrane potential. The steady-state activation and inactivation curves of Ito were not influenced by CGRP. The time course of Ito inactivation was satisfactorily fitted by two exponentials. Both the fast and the slow time constants of inactivation were voltage independent and were not influenced by CGRP. The effect of CGRP on Ito was concentration dependent with half-maximum inhibition at 99 nM. Chelerythrine, a selective inhibitor of protein kinase C, prevented the effect of CGRP on Ito. The data indicate that CGRP suppresses Ito in a concentration-dependent, but membrane potential-independent manner and that the effect is probably mediated via a protein kinase C-dependent pathway. PMID- 11205054 TI - Effects of endothelin-1 on calcium and potassium currents in undiseased human ventricular myocytes. AB - Endothelins have been reported to exert a wide range of electrophysiological effects in mammalian cardiac cells. These results are controversial and human data are not available. Our aim was to study the effects of endothelin-1 (ET-1, 8 nmol/l) on the L-type calcium current (ICa-L) and various potassium currents (rapid component of the delayed rectifier, IKr; transient outward current, Ito; and the inward rectifier K current, IK1) in isolated human ventricular cardiomyocytes. Cells were obtained from undiseased donor hearts using collagenase digestion via the segment perfusion technique. The whole-cell configuration of the patch-clamp technique was applied to measure ionic currents at 37 degrees C. ET-1 significantly decreased peak ICa-L from 10.2+/-0.6 to 6.8+/ 0.8 pA/pF at +5 mV (66.7% of control, P<0.05, n=5). This reduction of peak current was accompanied by a lengthening of inactivation. The voltage dependence of steady-state activation and inactivation was not altered by ET- 1. IKr, measured as tail current amplitudes at 40 mV, decreased from 0.31+/-0.02 to 0.06+/-0.02 pA/pF (20.3% of control, P<0.05, n=4) after exposure to ET-1. ET-1 failed to change the peak amplitude of Ito, measured at +50 mV (9.3+/-4.6 and 9.0+/-4.4 pA/pF before and after ET-1, respectively), or steady-state IK1 amplitude, measured at the end of a 400-ms hyperpolarization to -100 mV (3.6+/ 1.4 and 3.7+/-1.4 pA/pF, n=4). The present results indicate that in undiseased human ventricular myocytes ET-1 inhibits both ICa-L and IKr; however, the degree of suppression of the two currents is different. PMID- 11205055 TI - The three mechanisms of intracellular chloride accumulation in vascular smooth muscle of human umbilical and placental arteries. AB - Recordings of membrane potential (Em) and intracellular [Cl-] ([Cl-]i) were made from the smooth muscle of human umbilical and placental arteries, using double barrelled, ion-sensitive microelectrodes. In both arteries, [Cl-]i was above equilibrium with Em. In the umbilical artery, [Cl-]i was 33.8+/-0.9 mM (+/-SD, n=19) and Em -54.9+/-1.3 mV and in the placental artery respectively 35.1+/-0.7 mM (n=17) and -50.6+/-0.9 mV. In both arteries, [Cl-]i was reduced and Em hyperpolarised significantly by successive additions of 100 microM 4,4' diisothiocyanatodihydrostilbene-2,2'-disulphonic acid (DIDS), 10 microM bumetanide and 1 mM acetazolamide, thus revealing the presence of Cl-/HCO3- exchange, (Na+K+Cl) cotransport and "pump III". In the presence of all three inhibitors, [Cl-]i was in equilibrium with Em. As in earlier studies on rat arterial smooth and cardiac muscle, pump III was unaffected by DIDS, bumetanide, metolazone and the removal of Na+, partly inhibited by chlorothiazide and fully inhibited by ethacrynic acid. The results are discussed in terms of the possibility that of chloride accumulating systems may regulate vasomotor tone in the foetoplacental unit. PMID- 11205056 TI - Expression of the Na+/glucose co-transporter (SGLT1) in the intestine of domestic and wild ruminants. AB - The activity and abundance of the Na+/glucose co-transporter (SGLT1) was assessed in brush-border-membrane vesicles (BBMV) isolated from the intestine of grass- and roughage- (GR) consuming ruminants (sheep and dairy cattle), during the transition from the pre-ruminant to the mature ruminant state. The abundance of SGLT1 messenger ribonucleic acid (mRNA) was also compared in the intestinal tissue of the same animals. The dramatic developmental decline in the activity and expression of SGLT1 appears to be typical of GR-consuming ruminants and is coincident with the significant decline in the levels of lumenal monosaccharides. Expression of the ovine SGLT1 complementary deoxyribonucleic acid (cDNA) in Xenopus laevis oocytes confirmed that the isolated cDNA encodes for a functional Na+/glucose co-transporter. Determination of a bovine intestinal SGLT1 protein sequence (amino acids 347-658) indicated 99% similarity to the ovine SGLT1 protein with differences in the carboxyl terminus. In contrast to GR-consuming ruminants, the abundance of SGLT1 protein and SGLT1 mRNA remained significantly high in the intestine of ruminants in both the intermediate-mixed (IM) feeding goat and fallow deer and the concentrate-selecting (CS) moose and roe deer, dietary groups correlating with the availability of monosaccharides in the intestinal lumen. PMID- 11205057 TI - The harmonization of physiology teaching: a tool for its recognition in European countries. PMID- 11205058 TI - The influence of beta-adrenergic activation on noradrenergic alpha1 activation of rabbit afferent arterioles. AB - The aim of the present investigation was to examine the effect of beta-adrenergic stimulation on smooth muscle calcium concentration ([Ca2+]i) in resting conditions and after administration of norepinephrine (NE) to stimulate alpha adrenoceptors in isolated rabbit afferent arterioles loaded with the calcium sensitive fluorescent probe fura-2. [Ca2+]i was evaluated in the proximal and distal parts of the arterioles. NE (4x10(-7) M) increased [Ca2+]i in both these regions. The alpha1-adrenoceptor antagonist prazosin (10(-7) M) totally abolished the NE-induced increase in [Ca2+]i, while the alpha2-adrenoceptor antagonist yohimbine (5x10(-7) M) had no influence on the response to NE. When beta adrenoceptors were stimulated, using isoproterenol (10(-7) M), the NE-induced increase in [Ca2+]i was significantly lower in both regions. Activation of beta adrenoceptors with isoproterenol did not affect the [Ca2+]i increase in response to depolarization with K+. Since beta-adrenoceptor stimulation raises the smooth muscle cell levels of cAMP, an adenylate cyclase stimulator, forskolin (10(-5) M) was administered prior to NE application. This maneuver also blunted the increase in [Ca2+]i in both regions. We conclude that the calcium response to NE in the isolated rabbit afferent arteriole is mediated by an alpha1-adrenoceptor. beta Adrenoceptor stimulation and forskolin blunt the increase in [Ca2+]i induced by NE stimulation, indicating that cAMP counteracts the NE-induced activation of alpha1-adrenoceptors. PMID- 11205059 TI - A new transducer based on the evanescent field effect for high-resolution displacement and force measurements. AB - A new transducer, using the effect of frustrated total internal reflection of electromagnetic waves, was developed for displacement and force measurements in muscle research. The physical theory for this effect predicts the formation of an evanescent electromagnetic field in the gap between two separated optical surfaces. This evanescent electromagnetic field enables the transmission of light across the gap between the two media, an effect not contained in ray optics formalism. In the apparatus described here, the optical surfaces were obtained by bevelling 2 optical fibres to angles higher than the specific critical angle of the media used. Since the amount of transmitted light depends strongly on the distance between the surfaces, very small forces are detectable if one fibre is used as a cantilever. To test the transducer a small myofibrillar bundle (20 microm diameter) was mounted isometrically on it and contraction activated by release of "caged" Ca2+. Force and displacement steps of 180-220 nN and 9-11 nm respectively were measured with resolutions of 10 nN and 288 pm, respectively. From theoretical and practical considerations, it is expected that the presented principle will be able to achieve even much higher sensitivity for the determination of force (better than picoNewton) and distance (femtometre). PMID- 11205060 TI - Modulation of voltage-dependent facilitation of the T-type calcium current by sodium ion in isolated frog atrial cells. AB - Sodium ions have been reported to alter the permeation properties of L- and N type Ca2+ channels. Here in frog atrial cardiomyocytes under whole-cell patch clamp conditions, we have examined the effects of lowering the external Na+ concentration on the amplitude of T-type Ca2+ current, ICaT, and on the relief of its steady-state inactivation by large depolarizing prepulses, ICaT facilitation. A partial reduction in Na+ ion concentration did not significantly alter ICaT amplitude elicited at -50 mV. However, after a large depolarization, low- Na+ solutions enhanced the relief of inactivation and induced ICaT facilitation. This facilitation occurred independently of the divalent charge carrier, high intracellular Ca2+ buffering or the intracellular Na+ content. Its effects were additional to the beta-adrenergic effects mediated by a decrease of Gi/o-protein inhibitory tone. In Ca2+-free solution the very large T-type current, then carried by Na+ ions, showed only a weak relief of inactivation. In conclusion, ICaT facilitation--which, as previously reported, is modulated by the transient voltage-dependent relief of Gi-protein inhibitory tone--is further enhanced in a low-Na+ solution. In Ca2+-free solution, relief of inactivation due to re openings dependent on the divalent charge carrier is improbable. It thus appears that for a short while after a large depolarization, external Na+ compete with Ca2+ ions on permeation-controlling sites, so as to modulate channel re-openings and thus the amplitude of voltage-facilitated ICaT independently of the control exerted by the inhibitory G-protein. PMID- 11205061 TI - Evidence that aquaporin-8 is located in the basolateral membrane of rat submandibular gland acinar cells. AB - It is possible that, during primary saliva formation, aquaporins (AQPs) facilitate transcellular water flow across acinar cells to the lumina of salivary glands. In the rat submandibular gland (rSMG) AQP5 is localized in the apical membranes of acinar cells. The presence of a basolateral AQP in the same cell type has not been reported. We have therefore used immunofluorescence confocal microscopy to determine the subcellular localization of a newly discovered aquaporin, AQP8, in rSMG epithelial cells. The antibodies we used were made against the amino- or carboxyl-terminus (anti-rAQP8NT and anti-rAQP8CT, respectively) of an AQP8 cloned from rat pancreas and liver (rAQP8). Two lines of evidence suggest that both antibodies are suitable for immunolocalization studies. First, results of immunofluorescence confocal microscopy studies show that both antibodies bind to the plasma membranes of 293 cells infected with an adenovirus encoding rAQP8. Second, results of immunoblots of membranes from infected cells suggest that both antibodies bind to glycosylated and non glycosylated forms of rAQP8. When tested in frozen sections of rSMG, we could not detect the binding of anti-rAQP8NT to any membranes. In contrast, anti-rAQP8CT binds to the basolateral membranes of acinar (but not ductal) epithelia, suggesting that rAQP8 resides in the basolateral membranes of acinar cells. Lack of anti-rAQPNT binding to basolateral membranes suggests that this epitope is not available in the membranes. Our evidence for the basolateral localization of rAQP8 in acinar cells, coupled with previous findings that AQP5 is localized apically in the same cells, raises the possibility that water crosses the acinar epithelium through these channels during primary saliva formation. PMID- 11205062 TI - Presence and possible role of the spliced isoform of the P2X1 receptor in rat vascular smooth muscle cells. AB - An alternatively spliced isoform of the P2X1 receptor (P2X1a) was cloned from rat mesenteric artery. The spliced isoform does not have the 27 amino acids that are in the middle of the putative extracellular loop domain of the P2X1 original subunit (P2X1). Reverse transcriptase polymerase chain reaction (RT-PCR) revealed co-localization of P2X1a mRNA and P2X1 mRNA in vascular and other smooth muscle tissues and heart, but not in the spinal cord. In HEK293 cells transfected with P2X1 cDNA, ATP (1 microM) evoked an inward current which strongly desensitized, and an intense signal for GFP (green fluorescent protein) fused with P2X1 was detected at the membrane. Neither of these results was obtained in HEK293 cells expressing P2X1a alone. The fluorescent GFP signal was detected at the membrane when GFP-fused P2X1a was co-expressed with P2X1, and no significant difference in the ATP-activated current was noted between cells expressing P2X1 and those coexpressing P2X1 and P2X1a. These results indicate that the 27-amino-acid sequence (175-201) is important for protein trafficking to the membrane and for the formation of a functional P2X1 receptor. Our results also show that P2X1a is transported to the membrane when P2X1a is co-expressed with P2X1, although the co expression of P2X1a does not modify the channel's current properties. PMID- 11205063 TI - cAMP- and cGMP-independent stretch-induced changes in the contraction of rat atrium. AB - The stretch-induced changes in contraction force, cAMP and cGMP in isolated rat left atrium were studied. Increasing the diastolic intra-atrial pressure from 1 cmH2O to 8 cmH2O caused an immediate (<500 ms) increase in contraction force, the magnitude of which was 2.24+/-0.29 (n=6) times the force elicited by 1 cmH2O. This was followed by a slower, gradual increase of the force, which was maximal 8 min after the stretch (4.33+/-0.31, n=6). These phenomena were not accompanied by changes in the cAMP (n=24) or cGMP (n=24) concentrations within the tissue at any duration of stretch tested (2, 8, 20 and 36 min, n=6 at each time point). Furthermore, it was estimated that if the beta-adrenergic receptor agonist isoprenaline (100 nM) was used to produce an increase of the contraction force of the same magnitude as that induced by stretch, the cAMP concentration was greater (4.20+/-0.29 pmol/mg, n=5, P<0.001) when compared to that produced after 20 min of stretch (2.69+/-0.12 pmol/mg, n=6). Even without significantly changing the cGMP concentration, isoprenaline significantly increased the [cAMP]/[cGMP] ratio (3.4+/-0.36, n=5, P<0.01) compared to stretch (1.95+/-0.14, n=6). This result shows that in the rat atrium stretch does not regulate the production or breakdown of cyclic nucleotides (cAMP or cGMP). Thus it seems very unlikely that the effects of stretch on rat atrium function are caused by cAMP or cGMP. PMID- 11205064 TI - Hormones increase mRNA of cyclic-nucleotide-gated cation channels in airway epithelia. AB - Previous studies have shown that the mRNA of cyclic-nucleotide-gated nonselective cation (CNG) channels is expressed in rat airway epithelia and that these channels contribute to sodium-mediated short-circuit currents in cultured rat tracheal epithelia. Patch-clamp studies from human A549 cells indicate that these channels contribute to cGMP-stimulated L-cis-diltiazem- and dichlorobenzamil inhibited whole-cell sodium currents. This study demonstrates that mRNA for primary and secondary subunits of CNG channels, halphaCNG1 and hbetaCNG1 respectively, are expressed in several human airway cell lines, including normal and cystic fibrosis bronchial airway cells, in normal and cystic fibrosis tracheal airway cell lines and nasal polyp tissue from a cystic fibrosis patient. The mRNA of ralphaCNG1 in rat lung increased in response to increased circulating glucocorticoids and decreased in animals with lowered circulating glucocorticoids after aminoglutethimide treatment. Likewise the mRNA of halphaCNG1 increased in the presence of glucocorticoids in cultured alveolar airway cells. The mRNA of alphaCNG1 in rat lung was also increased in response to a low-salt diet and lowered in animals fed a high-salt diet. Likewise the mRNA of alphaCNG1 was increased in response to increased aldosterone and decreased in animals given spironolactone. These results suggest that mRNA for alphaCNG1 increases in response to elevated glucocorticoids or mineralocorticoids. Because alphaCNG1 is a functional sodium entry channel in both rat and human airway epithelial cells, if channel protein is also elevated this channel could mediate an increase in sodium absorption across lung epithelia in response to circulating hormones. PMID- 11205065 TI - Differential lusitropic responsiveness to beta-adrenergic stimulation in rat atrial and ventricular cardiac myocytes. AB - Cardiac myocyte relaxation is brought about mainly through Ca2+ uptake into the sarcoplasmic reticulum (SR) by a Ca2+-ATPase isoform, SERCA2a. Its activity is modulated by another protein, phospholamban (PLB). The levels of both proteins differ in some mammals between atrial and ventricular myocardium and this may lead to differences in relaxation, especially under stimulatory conditions. At a concentration of 100 nM, the beta-adrenergic agonist isoprenaline (ISO) accelerates the relaxation of rat papillary muscle more than that of the left atria (16.4 versus 4.0% hastening of time to 50% relaxation, respectively). Ventricular myocytes were 24.7% quicker in reaching 50% of their diastolic length after contraction when treated with ISO compared to atrial myocytes, which were only 3.6% faster. Ca2+ fluorescence transients were also abbreviated in ventricular compared to atrial myocytes exposed to ISO (41.9 versus 25.2% hastening of time to 50% peak Ca2+ respectively). Ca2+ uptake into ventricular SR vesicles was increased by 13% in the presence of protein kinase A while that into atrial SR vesicles remained unaffected. Western blotting analysis revealed 23% less SERCA2a protein, but 76% more PLB in ventricular compared to atrial tissue. We conclude that the distinct levels of SERCA2a and PLB in ventricular and atrial myocardium are responsible for the differential modulation of the relaxation process arising from beta-adrenergic stimulation in single rat atrial and ventricular myocytes. PMID- 11205066 TI - Flunarizine pretreatment attenuates hyperthermia-induced extravasation in rats. AB - Previous work has established that there is an increase in endothelial permeability in hyperthermic rats. This work assessed the potential of the calcium channel blocker (E)-1-bis(4-fluorophenyl)methyl-4-(3-phenyl-2 propenyl)piperazine dihydrochloride (flunarizine) as a pretreatment to ameliorate this extravasation. Five groups of male rats (n=12 rats per group, 400-500 g) were given 0, 0.3, 1, 2, or 3 mg/kg flunarizine (FL0, FL0.3, FL1, FL2, and FL3, respectively) by gavage 30 min prior to induction of hyperthermia. Hyperthermia was achieved by placing unrestrained animals in their own cages in a chamber maintained at 41.5 degrees C until a core temperature (Tc) of 42.6 degrees C was attained. Then, 25 mg/kg of Evans blue in saline was administered via a jugular cannula. After 15 min the animals were anesthetized, exsanguinated, tissues removed and washed in saline, and Evans blue extracted with formamide. As the dose of flunarizine was increased, there was a significant (P<0.05) reduction of Evans blue recovered from the liver, kidney, lung, spleen, and intestinal tissue. Endurance time in the heat to reach a Tc of 42.6 degrees C increased significantly from 194+/-39 min (mean+/-SD) with FL0 to 275+/-33 min with FL1, but decreased again with FL2 (206+/-42) and FL3 (199+/-60). Thus, flunarizine pretreatment attenuated hyperthermia-induced extravasation, and 1 mg/kg flunarizine markedly increased the tolerance time to heat exposure. PMID- 11205067 TI - Acute differential regulation by corticosteroids of epithelial sodium channel subunit and Nedd4 mRNA levels in the distal colon. AB - The molecular mechanisms by which corticosteroids affect fluid and electrolyte balance have yet to be fully elucidated. The apical amiloride-sensitive electrogenic epithelial sodium channel (ENaC) has been shown to have a central role in corticosteroid-mediated sodium transport in the distal colon. The acute response of the alpha-, beta- and gammaENaC subunit genes to a single parenteral dose of aldosterone or dexamethasone was examined in the rat distal colon in vivo. The response of the Nedd4 gene, whose product is involved in channel turnover, was also examined. Whilst the alphaENaC and Nedd4 genes showed no significant response to either steroid, both the beta- and gammaENaC mRNA levels were increased acutely by both aldosterone and dexamethasone. The gammaENaC mRNA appears to have a very short half-life. Use of the highly selective glucocorticoid receptor agonist RU28362 confirmed that the response was mediated by both the mineralocorticoid and glucocorticoid receptors. PMID- 11205068 TI - Glue solvent inhalation impairs host resistance to Mycobacterium bovis-induced infection in hamsters. AB - Industrial organic solvents present in glue are among the common used psychotropic drugs in Brazil and perhaps worldwide; but few data are available concerning the toxic effects of glue sniffing, with almost no information about immunotoxicity. This seems interesting because several drugs and environmental chemicals are recognized as potential immunotoxicants. The present study investigated the effects of forced inhalation of a toluene/n-hexane 1:1 mixture on hamster resistance to Mycobacterium bovis. Adult hamsters were divided at random into 3 equal groups. Animals of Groups E and E inhaled the mixture of toluene/n-hexane twice daily for 37 d. Group C was placed for the same period of time in identical chambers free of solvents. Two days after the beginning of the experiment, Groups E and C were injected ip with 0.5 ml of an activated suspension of M. bovis; Group E received the same volume of a control solution. Hamsters inhaling the toluene/n-hexane mixture (E) exhibited increased weight loss, increased scores of M. bovis colony forming units isolated from liver, lung and spleen, increased granulomatous areas in the liver, lung and spleen. Inhalation of the toluene/n-hexane mixture for 37 d also increased serum cortisol compared to control hamsters. Tuberculosis is an infection with an intracellular bacterium in which sensitivity is determined mainly by host response. The present data demonstrated impaired defense against M. bovis in hamsters inhaling a toluene/n-hexane mixture for 37 d. Since macrophages are the architectural and functional units of the granulomas in tuberculosis, and no data were found about glue solvent effects on cellular immunity, the present data suggest an indirect effect of glue solvents on macrophage/lymphocyte activity via stress induction and central nervous system stimulation of hormonal (ACTH/cortisol) secretion and/or autonomic nervous system activity. PMID- 11205069 TI - Ferrous sulfate adsorption by activated charcoal. AB - Although activated charcoal is thought to not appreciably adsorb iron salts, previous in vitro work indicates some adsorption of iron. This study characterized the adsorptive capacity of activated charcoal for ferrous sulfate at 3 pH environments. Langmuir adsorption isotherms were determined with a fixed amount of iron in the reaction vessels. Activated charcoal USP (20, 40, 60, 80, 100, or 120 mg) was placed in plastic tubes to which were added 1 of 3 different simulated gastrointestinal fluids (pH = 1.5, 4.5, or 7.5) and 1.49% ferrous sulfate in water. The reaction vessels were agitated and immersed in a water bath at 37 C for 30 min. Each series was performed in triplicate. Following temperature eQuilibration filtration yielded an aliquot that was assayed for iron by atomic absorption spectrophotometry. Adsorptive capacities (mean +/- SD) of activated charcoal for ferrous sulfate (mg elemental iron/g charcoal) at pH 4.5 (102.96+/-4.49) and pH 7.5 (100.94+/-19.02) were higher (P<0.01) than at pH 1.5 ( 0.01+/-0.26). At pH 1.5 iron was not appreciably adsorbed by activated charcoal. Activated charcoal adsorbed ferrous sulfate to a greater extent at pH environments where iron is typically absorbed from the gastrointestinal tract. These results indicate that activated charcoal may prove an effective therapy for acute iron poisoning and further investigation is warranted. PMID- 11205070 TI - Systemic toxicity from repeated cutaneous contact with 2,4-pentanedione. AB - 2,4-Pentanedione (2,4 PD; CAS Number 123-54-6) is an industrial chemical with potential for skin contact. Repeated exposure studies by peroral and inhalation routes have shown central neurotoxicity and possible effects on the immune system. To determine the likelihood for systemic toxicity by cutaneous contact with 2,4-PD, a short-term repeated skin contact study was conducted in New Zealand white rabbits. The planned protocol was for dosing, with 0.5, 1.0 and 1.5 ml undiluted 2,4-PD by 6 h occlusive contact/d for 9 d; these were equivalent to dosages of 244, 975 and 1463 mg/kg/d. A dosage-related skin irritation was seen macroscopically and by light microscopy, which was minimal at the low dosage. Mortalities occurred at the mid (1/6 males, 3/6 females) and high dosages (5/12 males, 7/12 females), with deaths between the 2nd and 5th dosing day. In view of these mortalities and signs, dosing of the mid and high dose animals was discontinued, and survivors were kept to the end of the dosing period. Signs at the mid and high dosage included hypoactivity, tremors, convulsions, uncoordinated movements and prostration, and appeared between the 2nd and 4th dose. Body weight gain and food consumption were reduced for the mid and high dosage groups. Increased hemoglobin, hematocrit and erythrocyte counts may have been associated with dehydration, and increased heterophil count with cutaneous inflammation. Several serum biochemical changes reflected cutaneous irritation, and high creatine kinase activity was probably a consequence of convulsions. Immune effects included decreased lymphocyte counts and lymphoid necrosis in spleen and thymus. Central neuropathology in the mid and high dosages was seen as hemorrhages and neuronal degeneration, the latter principally in piriform cortex, globus pallidus and hippocampus. No peripheral neuropathy was present. 244 mg/kg/d was the no-effects dosage for systemic toxicity. This study confirmed a potential for systemic toxicity, principally central neurotoxicity, from percutaneous absorption of 2,4-PD. PMID- 11205071 TI - Cholinesterase activity:muscarinic receptor ratios in canine and feline brains. AB - In response to findings that brain cholinesterase (ChE): muscarinic cholinergic receptor density (mChR) ratio is highly conserved between bird species (I), this study investigated the conservation of brain ChE:mChR between 2 mammalian species. Whole brains of 7 normal greyhounds, 14 normal non-greyhound dogs, and 8 normal cats, were assayed for ChE, mChR and protein. The same assays were made on cerebrum, cerebellum and brainstem from the greyhounds and 6 of the non-greyhound dogs. The Ellman assay was used to measure serum ChE activity, mChR were labelled with tritiated quinuclidinyl benzilate, and protein was measured by Lowry assay. Brain ChE:mChR was not highly conserved between the species. There was a statistically significant difference in brain mChR between greyhounds and non greyhounds but this did not translate to a statistically significant difference in mean ChE:mChR. Measurement of ChE:mChR is unlikely to be useful in endangered carnivores for which normal ChE levels are unknown, because it cannot be assumed that endangered species would have the same ChE:mChR as their domestic relatives. PMID- 11205072 TI - Squamous epithelial proliferation in the jaws of mink fed diets containing 3,3',4,4',5-pentachlorobiphenyl (PCB 126) or 2,3,7,8-tetrachlorodibenzo-P-dioxin (TCDD). AB - Previous research has shown that ingestion of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) by juvenile mink (kits) caused a lesion in the mandible and maxilla that consisted of proliferation of sQuamous epithelium in the periodontal ligament, osteolysis of adjacent alveolar bone, and loose and displaced teeth. Similar, but less severe changes, developed in adult mink fed 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). The present study was conducted to compare similarities and differences of the lesion within the jaws of mink fed these 2 polyhalogenated hydrocarbons. Diets containing 24 ppb PCB 126 or 2.4 ppb TCDD were fed to 6-w-old kits for 36 d. Similar diets were fed to 12-w-old kits for 35 d. Some of these mink were then fed untreated feed for an additional 50 d. All mink treated with PCB 126 or TCDD had reductions in body weight gains which were more severe in the 6-w-old kits than the 12-week-old kits. By 28 days of exposure, many of the 6- and 12-week-old mink treated with PCB 126 or TCDD had loose and displaced incisor teeth. Canine teeth were grossly more prominant. Radiographs showed maxillary and mandibular osteolysis with lysis of the lamina dura in treated mink. Withdrawal of the toxicants from the diets of the 12-w-old mink failed to alleviate the lesions, which continued to be progressively more severe. PMID- 11205073 TI - Anagallis arvensis poisoning in cattle and sheep in Uruguay. AB - Outbreaks of Anagallis arvensis poisoning were observed from 1994 to 1998 in cattle and sheep in Uruguay during December and January. Cattle morbidity varied between 3.2 and 53.2% and lethality 42.6 and 100%. Sheep morbidity was 2.8 to 42.9% and lethality 81.3 to 100%. Nine outbreaks occurred on barley and wheat stubble, and 1 in a field previousy ploughed but not cultivated. Clinical signs were weakness, staggers, diarrhea (sometimes bloody), coma, and death. Serum levels of creatinine and urea were elevated. Gross lesions were characterized by sc petechiae, fluid in body cavities, mesenteric and perirenal edema, yellowish or pale kidneys with petechiae on the cortex, esophageal erosive lesions or ulcers, and hemorrhagic abomasitis and enteritis. Severe nephrosis was observed histologically. The green plant collected in a field where an outbreak occurred was administered to 2 sheep at doses of 160 and 224 g/kg bw and produced clinical signs and pathology similar to those observed in field cases. PMID- 11205074 TI - Paraquat poisoning in a family. AB - A familial occurrence of acute paraquat (PQ) poisoning is reported. The mother administered a PQ solution to their 3 children aged 8 y, 6 y and 15 mo and then ingested an unknown amount of the herbicide herself. In the absence of history or diagnostic signs, the poisoning was initially misdiagnosed as gastroenteritis. Thirty h after the ingestions, serum PQ concentrations of the children were 60, <6 and 25 ng/ml respectively. Hemoperfusion was performed on all patients, and 2 of the children also received plasmapheresis and erythropheresis. The 3 children recovered fully but the mother died. According to these patients' data, the extracorporeal techniques had little effect on PQ removal, and the decreases in serum PQ were related to its urinary excretion. PMID- 11205075 TI - Intermediate syndrome secondary to ingestion of chlorpiriphos. AB - A rural-area resident male patient deliberately ingested chlorpiriphos, an organophosphate insecticide. Although presented with cholinergic symptoms initially, he suffered general condition deterioration after 4 d characterized by muscular weakness, hypotonia, arreflexia and recumbent dyspnea requiring ventilatory support. These clinical manifestations occur from liposoluble organophosphates or metabolites with long-lasting half time, causeing delayed inhibition of acetylcholinesterase and subsequent burn out of the neuromuscular junction from acetylcholine overstimulation. PMID- 11205076 TI - A fatal case of apparent water hemlock poisoning. AB - A 14-y-o North American native boy died 20 h after ingesting "wild carrot". He was gathering edible plants with his family on Canadian Thanksgiving. A sample of the plant he ingested couldn't be positively identified but it contained cicutoxin on chromatography. Bioassay caused death in mice which demonstrated clinical signs similar to water hemlock (Cicuta maculata) poisonings. Cicutoxin could not be demonstrated in postmortem tissue or gastric lavage. The boy's clinical signs and laboratory tests were consistent with other reported cases of this poisoning. PMID- 11205077 TI - Field observations of Ateleia glazioviana poisoning in cattle in Southern Brazil. AB - Ateleia glazioviana is an important poisonous plant from southern Brazil. Heavy losses in cattle from this region occur each year due to ingestion of the plant. The epidemiological, clinical, gross and histopathological features of A. glazioviana poisoning in cattle are described here from a 5-year field survey in southern Brazil. A. glazioviana poisoning in cattle induces 3 clinical presentations: abortions, disease characterized by lethargy, and cardiac failure. The latter is associated with marked necrosis and fibrosis of the myocardium and can cause sudden death or congestive heart failure. PMID- 11205078 TI - Prolonged coma and loss of brainstem reflexes following amitriptyline overdose. AB - Severe tricyclic antidepressant (TCA) overdose is generally manifested by cardiovascular and/or central nervous system toxicity. Although the majority of patients who are comatose following these overdoses regain consciousness within 24 h, this case had 5-days of coma with associated loss of brainstem reflexes. Severe central nervous system depression can occur as a sole manifestation of TCA overdose without concomitant cardiovascular toxicity. PMID- 11205079 TI - Implementation of Toxicall: impact on documentation. AB - On January 1, 1999, the Washington Poison Center implemented Toxicall; 6 mo later we measured its impact on time devoted by staff for telephone interchange, information retrieval from other than Poisindex, and documentation, and to compare it with prior studies of our conventional paper-pencil system. Previous "time and motion" studies over the past decade, using random alarm devices (Devilbiss Electronics) provided data for comparative purposes. We developed a computer-based alarm system for timing and station selection and for recording observed behaviors. Over a 6-w period, 211 calls were analyzed; the percentage of time involved for each call was compared to a 1993 study. An increased, rather than anticipated decreased, documentation effort was observed (p< 0.05), but staff participation in activities other than those listed fell dramatically suggesting increased staff efficiency. Although documentation efforts consume so much time, Toxicall provided the non-debatable benefit of eliminating illegible staff handwriting! PMID- 11205080 TI - Decoding "drug imprints" at the millennium: a proposal to increase accuracy and reduce costs. AB - The State of Washington mandated the use of imprints on all prescription drugs in 1980 and for "OTC's" in 1991. The FDA implemented federal requirements in 1995. Unfortunately, the FDA permitted the continued use of symbols, logotypes, and trademarks as code components, limiting the use of automated recognition systems. Analyses of several week-long samples of phone inquiries documented imprinting calls, the staff's ability to respond with an identification, the information sources used, and apparent reasons for any failure. In the first week we received 666 decoding requests, which when projected for the year amounted to > 25,000 calls. A review of 1999 data exceeded that number. Staff was able to reach drug identification in 93.8% of inquiries. Uninterpretable symbols and absence of code listings contributed to the 36 failures. Projecting over the US suggested as many as 1.25 million calls costing poison centers $25 million/y. A touch-tone telephone or website response system could permit automated responses. Neither solution is feasible without the elimination of symbols or logotypes when using an exclusively alpha-numeric code. PMID- 11205081 TI - Pulmonary diseases caused by airborne contaminants in swine confinement buildings. AB - Exposure to toxic gases and particles or dusts while working or living in confinement animal systems pose a pulmonary health hazard. The severity of lung impairment from exposure to such environment is investigated using intratracheal instillation, intratracheal nebulization, and inhalation procedures. Ability to deliver particles with intratracheal instillation that are evenly distributed throughout the lung depends on the material used for injection. Pulmonary histopathology reflects anatomic changes following inhalation or instillation of chemicals or particles. Endobronchial saline washings of bronchioles and alveoli allow measurement of markers of pulmonary inflammation such as total nucleated cell (leukocyte) counts and those of macrophages, neutrophils and lymphocytes; TNF-alpha, and collagen concentration are used to further evaluate pulmonary response to endotoxin or dust exposure. Alveolar epithelial cells have an important role in clearing pulmonary fluid and maintaining the structure of lung tissue. After repeated exposure, damage to epithelial cells may result in their death, causing edema and collagen deposition that may lead to fibrosis. PMID- 11205082 TI - Quoth the EPA--ever less! PMID- 11205083 TI - Agonistic and antagonistic effects of zearalenone, an etrogenic mycotoxin, on SKN, HHUA, and HepG2 human cancer cell lines. AB - Zearalenone (ZEA) is a nonsteroidal estrogenic compound mainly produced by the molds Fusarium graminearium and Fusarium culmorum found in a variety of host plants and soil debris around the world. ZEA is usualy non-lethal to animals but is important to livestock producers because its hyperestrogenic effects adversely influence the reproductive performance of animals. There have been suggestions of possible involvement of ZEA in the progression of breast malignancies and tumors of the female reproductive tract in humans. The toxic or stimulatory effects of ZEA and its metabolites alpha-zearalenol and 17-beta-estradiol on SKN, HHUAand HepG2 cells were studied using rapid colorimetric MTT assay. In general, both concentrations of 17-beta-estradiol (100M and 10 nM) were toxic to SKN and HHUA cell cultures. Both ZEA and alpha-zearalenol stimulated the proliferation of SKN and HHUA cells. On HepG2 cells, lower concentrations (10 nM) of 17-beta-estradiol and higher concentrations (100 microM) of ZEA exhibited toxic effects, whereas treatment with higher concentrations of 17-beta-estradiol and lower concentration of ZEA did not show toxic effects. A dose dependent antagonistic effect was observed when the cell cultures were pre-incubated with ICI 182,780, a synthetic estrogen receptor blocker, before estradiol or mycotoxin treatments. PMID- 11205084 TI - The concept of placebo and general practice. Is it time to avoid the word placebo? PMID- 11205085 TI - Report from University of Bristol. PMID- 11205086 TI - Significant event auditing. AB - Significant event auditing has been described for 5 years and it is slowly gaining credibility as an effective method of quality assurance in British general practice. This paper describes what it is, what its background is, how it is done and whether it is effective. While it needs a positive team culture - and therefore may not suit every practice - where it is used it appears to be a useful adjunct to a clinical audit programme. PMID- 11205087 TI - Screening for hearing and visual loss among elderly with questionnaires and tests: which method is the most convincing for action? AB - OBJECTIVE: To examine the extent to which self-report and performance-based measures identify the same people, and also whether one of these methods any more than the other induces the general practitioner (GP) to offer a patient help? DESIGN: Comparison of tests and questionnaire in a screening programme for hearing and visual loss. SETTING: Twelve general practices in the western part of The Netherlands. PATIENTS: 1121 people 75 years of age and older. MAIN OUTCOME MEASURES: Hearing loss according to the whispered voice test and two questions (Q1, Q2) and visual loss according to the Snellen and low vision charts and two questions (Q3, Q4). The extent to which test and questions influence the GP's judgment regarding intervention is calculated using logistic regression. RESULTS: For hearing loss, the concordance of the whispered voice test with Q1 was 67%, and with Q2, 71%. For visual loss, the concordance of the Snellen chart with Q3 was 79% and of the Low Vision Chart with Q4, 69%. For hearing loss, the results of the test were noticeably more significant for the GP in offering help than the answers to the questions, and for visual loss the results of the Snellen chart slightly more convincing than the answers to the questions. CONCLUSION: When in a screening programme with simple instruments for visual and hearing loss the choice has to be made between questionnaire and tests, the tests will be the best choice. PMID- 11205088 TI - Clinical findings in a population with back pain. Relation to one-year outcome and long-term sick leave. AB - OBJECTIVE: To investigate whether physical examination findings can be used in predicting recovery from back pain and new episodes of sick leave. DESIGN: One year prospective study of a single cohort. SETTINGS: Semi-rural Swedish county. POPULATION: A cross-section of a general population with back pain (207 women, 176 men) between 20 and 59 years of age. MAIN OUTCOME MEASURES: Cumulative incidence of sick leave due to back pain, cumulative incidence of sick leave due to back pain > 30 days, incidence of recovery from back pain. RESULTS: For recovery from pain, the absence of tenderness in the trapezius muscle (OR 0.33; CI 0.1-0.5) was predictive. New sick leave was predicted by tenderness in the trapezius muscle (OR 2.67; CI 1.5-4.9), and had a tendency to be associated with a flattened lumbar lordosis and a restricted cervical range of motion. For long term sick leave, the same findings and also observation of scoliosis (OR 3.44; CI 1.1-10.5) were predictive. CONCLUSION: There are subgroups with back pain predisposed to development of more persistent symptoms and a higher risk for sick listing. PMID- 11205089 TI - Effects on physicians' sick-listing practice of an administrative reform narrowing sick-listing benefits. AB - OBJECTIVE: To find out whether administrative changes regulating sick-listing benefits affect sick-listing practice among physicians in hospitals and primary health care. SETTING: New sick-listing cases from four social security offices in mid-Sweden. DESIGN: A natural experiment design was used with a sample of newly started sick-listed cases collected 6 months before a sick-listing reform and a further sample taken 6 months after. The data were collected in a 1-year follow up period in both samples. MAIN OUTCOME MEASURES: Net days of sick-listing and percentage partial sick-listings. Compliance by doctors in providing information asked for in sickness certification forms. RESULTS: Doctors filled in the forms more completely after the reform than they did before it. There was an inverse correlation between completeness of information and length of sick-listing. When potential confounding factors were taken into account, no change was seen in the proportion of partial sick-listing, in the mean number of net days of sick listing or in the distribution of length of sick-listing periods. The proportion of all sick-listings made by general practitioners increased. CONCLUSIONS: Administrative changes restricting sick-listing benefits did change some aspects of sick-listing practice but had no effect on length of sick-listing. PMID- 11205090 TI - Wound management for 287 patients with chronic leg ulcers demands 12 full-time nurses. Leg ulcer epidemiology and care in a well-defined population in southern Sweden. AB - OBJECTIVE: To study the prevalence, aetiology and treatment of chronic leg and foot ulcers, and to estimate the nurse's time in wound management. DESIGN: A structured questionnaire with 19 questions about chronic ulcers and wound management was sent to all district and community nurses in the county during 1 week in March 1998. A similar questionnaire has been administered regularly since 1986. SETTING: Primary and community care in the county of Blekinge, Sweden, with a population of 1,51,610. PATIENTS: 287 patients with chronic leg and foot ulcers were identified during the week studied. MAIN OUTCOME MEASURES: Prevalence of leg and foot ulcers, ulcer aetiology, treatment of ulcers and wound management time. RESULTS: The estimated prevalence of chronic leg and foot ulcers was 0.19%. Venous ulcers were the most common (38%), of which 87% were treated with some form of compression therapy. Seven percent of the nurse's workload was devoted to ulcer care. During the period 1986 to 1998, ulcers with missing or unknown aetiology decreased from 31% to 6% and ulcers with a duration of more than 2 years from 44% to 27%, while treatment time per ulcer decreased from 2.1 to 1.7 hours/week. CONCLUSION: Monitoring standards for ulcer aetiology through repeated questionnaires seems to ensure more accurate diagnoses. Thorough and detailed information about treatment time documents the workload for wound management. PMID- 11205091 TI - Drug treatment of heart failure--do nursing-home residents deserve better? AB - OBJECTIVE: To describe and assess drug treatment of heart failure (HF) in nursing home residents. DESIGN: Descriptive cross-sectional study. Individual patient information was obtained from the medical records and drug-dispensing cards. SETTING: Nursing homes in Bergen, Norway. MAIN OUTCOME MEASURES: Demographic data, diagnostic data (main diagnoses, diagnostic indications for the drugs used), medications (drugs, dosage and duration of use). RESULTS: Data were gathered from 23 of 27 obtainable institutions representing 1552 residents (86% of the Bergen nursing-home population); 469 (30%) of the residents used drugs for HF, the majority of whom (293 patients) were treated with furosemide only. Supplementary angiotensin-converting enzyme (ACE) inhibitors (predominantly in sub-target doses) were provided to 17% of the HF patients. About one out of four used drug combinations which we considered to be potentially harmful for HF patients. CONCLUSIONS: ACE inhibitors are probably under-utilised for HF in nursing-home residents. Potentially harmful drug combinations commonly occur. Both diagnosis and drug treatment for HF should be challenged in the nursing-home setting. PMID- 11205092 TI - How well are patients with atherosclerotic disease treated? Secondary prevention in primary care. AB - OBJECTIVE: To examine changing trends in the field of secondary prevention of atherosclerotic disease in Norwegian general practice. DESIGN: A multipractice survey of consecutive patients with atherosclerotic disease consulting general practitioners in 1994/95 compared with a similar survey in 1996/97. SETTING: Primary health care. SUBJECTS: 707 patients attending 31 general practitioners in 1994/95 and 1353 patients attending 63 general practitioners in 1996/97. MAIN OUTCOME MEASURES: The patients were examined and interviewed for risk factors and pharmacological treatment. RESULTS: In 1994/95, 18% of the patients had been prescribed a lipid-lowering agent as opposed to 55% in the later survey. Consequently, the average level of LDL cholesterol in the 1996/97 population was 19% lower than in the 1994/95 population (3.8 mmol/l vs 4.7 mmol/l), which may imply a marked risk reduction. Aspirin and beta-blockers were prescribed to approximately 50% of the patients in both surveys. Diabetic patients had the same drug prescription rate and lipid profile as non-diabetics. In both surveys, about 25% of the patients were smokers. CONCLUSION: Secondary prevention in the majority of patients with atherosclerotic disease though ameliorating is still unsatisfactory. More attention is needed to achieve and sustain treatment goals. PMID- 11205093 TI - Effectiveness of a co-ordinated nation-wide programme to improve influenza immunisation rates in The Netherlands. AB - OBJECTIVE: To assess t he effectiveness of a nation-widemultifaceted intervention programme involving general practitioners (GPs) on influenza immunisation practice. DESIGN: Pragmatic before-after trial using pre- and post-measurement questionnaires. SETTING AND SUBJECTS: Random sample of Dutch general practices. INTERVENTION: During a 2.5-year period (1995-1997) a variety of methods was implemented to enhance physician adoption of the immunisation guideline, including employment of facilitators, information-based methods, small-group consensus meetings, individual instructions and introduction of supportive computer software. MAIN OUTCOME MEASURES: Influenza immunisation practice and influenza vaccine uptake. RESULTS: In 988 practices all influenza vaccination characteristics markedly improved from 1995 to 1997. The most significant changes were found in computerised marking of high-risk patients (from 54% to 82% of practices), computerised selection (41% to 77%) and sending personal reminders (40% to 77%). Vaccine uptake increased from 9% to 16% of the practice population (78% increase, p < 0.001). Uptake was most prominent in urban and single-handed practices and in those with more patients insured through the National Health Service, low GP workload and low baseline uptake. CONCLUSION: Our data suggest that a co-ordinated approach involving primary care physicians can succeed in enlarging the public health impact of a population-based preventive measure. PMID- 11205094 TI - Standardised procedures can improve the validity of susceptibility testing of uropathogenic bacteria in general practice. AB - OBJECTIVE: To investigate whether the validity of susceptibility testing in general practice would improve when preceded by an intervention. INTERVENTION: Instruction in standardised susceptibility testing procedures given by laboratory instructors. METHOD: Urine specimens containing monocultures of typical uropathogenic bacteria were sent to 23 general practices before and after the intervention. Practices performed susceptibility testing by the Sensicult and the Iso-Res agar methods and the validity of the results before and after the intervention was compared. Results from susceptibility testing at the bacteriological laboratory, Odense University Hospital, were used as gold standard. RESULTS: The median frequency of correct results increased from 82% to 98% for susceptibility testing based on Sensicult (p = 0.001) and from 90% to 96% based on Iso-Res agar (p = 0.05). CONCLUSION: The validity of susceptibility testing in general practice improves when preceded by instruction in standardised procedures. PMID- 11205095 TI - Smoking cessation. A comparative, randomised study between management in general practice and the behavioural programme SmokEnders. AB - OBJECTIVE: To compare the effectiveness of two different stop smoking interventions. DESIGN: A randomised, controlled trial. Results based on intention to treat. SETTING: Three towns in the south-eastern part of Norway. INTERVENTIONS: Visits to GP for "practice as usual" (GP group) or participation in the behavioural programme SmokEnders (SE group) with follow-up 2 weeks, 2 months and 1 year after an agreed stopping date. SUBJECTS: 139 smokers recruited through open invitation. MAIN OUTCOME MEASURE: Self-reported smoking stop rate 2 weeks, 2 months and 1 year after an agreed stopping date, completed with biochemical indicators by the 1-year registration. RESULTS: Two weeks after the agreed cessation date, 10/70 (14%) of the GP group and 46/69 (67%) of the SE group had stopped smoking. After 2 months, 9/70 (13%) in the GP group and 37/69 (54%) in the SE group were non-smokers. One year after cessation 5/70 (7%) in the GP group and 21/69 (30%) in the SE group were non-smokers. CONCLUSIONS: Both interventions were effective as measured by the smoking cessation rate. However, the intervention in the SE group was considerably more effective than in the GP group, which suffered from a sizeable number of drop-outs. PMID- 11205096 TI - Quality improvement in primary health care using computerised journal, exemplified by a smoking cessation programme for diabetic patients. AB - OBJECTIVE: To study the possibility of using the computerised journal for quality improvement in diabetes care. DESIGN: The computerised journal was used to reach all diabetic smokers aged 30-75 years and to invite them to a structured smoking cessation programme. The follow-up time was 18 months. SETTING: Habo, a Swedish community with 9600 inhabitants, with one primary health care centre. SUBJECTS: 147 subjects, aged 30-75 years, were registered with the diagnosis of diabetes mellitus in the computerised journal at the primary health care centre. Altogetber 25 of these patients were registered as smokers in the journal. All of them were invited to a smoking cessation group. RESULTS: Information about smoking habits in the journal was available for all but 11%. After 18 months' follow-up, 9 of the 14 patients (64%) who started in the smoking cessation group had become non-smokers. Of those 11 subjects who did not attend the group, 6 had stopped smoking during the follow-up time in spite of not participating in the structured programme. CONCLUSION: The computerised journal is a useful tool for quality improvement, giving the opportunity for directed preventive efforts on selected patient groups. PMID- 11205097 TI - Author index to volume 85, 2000. PMID- 11205098 TI - Deletions near the N-terminus of HIV-1 Rev reduce RNA binding affinity and dominantly interfere with Rev function irrespective of the RNA target. AB - The contributions of the near N-terminal residues of Rev protein of HIV were investigated by analyzing N-terminal deletions of Rev in the context of a Rev/MS C fusion protein that can bind and activate both the Rev responsive element (RRE) and the MS2 phage translational operator RNAs. Rev/MS-C fusion proteins deleted for residues 3-19 of Rev retained trans-activation potential for both RRE and MS2 targets. Coincidentally, peptides spanning residues 17-87 or 22-85 were functionally competent for trans-activation of RRE containing HIV-1 gag mRNA. Deletion of residues 18-24 of Rev in the Rev/MS-C fusion protein abolished the activation potential for both RRE and MS2 targets, although this mutant was competent for specific RNA binding, protein multimerization, and nuclear and nucleolar localization. Four mutants dominantly interfering with Rev activation of RRE were mapped near the N-terminus of Rev; (i) between residues 18 and 24, (ii) 25-34, (iii) 43-50, and (iv) 51-60. Of these, the mutant lacking residues 18 24 was a novel trans-dominant inhibitor of Rev and Rev/MS-C for activation of RRE or MS2 RNA, while the oligomerization domain mutants mapping between residues 25 34 or 51-60 inhibited the activation of RRE rather than MS2 RNA. PMID- 11205099 TI - Cloning and sequencing of columbid circovirus (coCV), a new circovirus from pigeons. AB - The complete nucleotide sequence of columbid circovirus (CoCV) isolated from pigeons is described. CoCV was amplified using a consensus primer PCR approach directed against conserved sequences within the rep genes of vertebrate circoviruses. The genome of CoCV is circular and 2037 nt in size. It displays 55% homology to the genome of psittacine beak and feather disease virus and is more distantly related (< 40% homology) to porcine circovirus type 1 and 2. Two major open reading frames were identified, encoding the replicase and the putative capsid protein of CoCV. A region similar to the origin of replication of other circoviruses was found: it encompasses a stem-loop structure with the nonamer 5' TAGTATTAC, conserved in circo-, nano- and geminiviruses. Phylogenetic analyses suggest classification of CoCV as member of the genus Circovirus of the virus family Circoviridae. PMID- 11205100 TI - Isolation and characterization of simian immunodeficiency virus variants that are resistant to nonnucleoside reverse transcriptase inhibitors. AB - Non-nucleoside reverse transcriptase inhibitors (NNRTIs) act quite specifically on human immunodeficiency virus type 1 (HIV-1). In general, they are not effective on human immunodeficiency virus type 2 (HIV-2) or simian immunodeficiency virus (SIV). Only SIV strains from African green monkeys are sensitive to several NNRTIs. Here we isolated NNRTI- and 3TC-resistant SIVagm variants. Viruses resistant to delavirdine contained V112I and M231I substitutions, while those resistant to 3TC contained a M 185I substitution. These amino acids are highly conserved in HIV-1, HIV-2, SIVmac and SIVagm, and the M184I (M185I in SIVagm) substitution was observed in 3TC-resistant HIV-1 and SIVmac. The roles of the observed mutations in NNRTI-resistance of SIVagm and HIV 1 were further confirmed by site-directed mutagenesis. The present results have provided a new insight into the common mechanism of sensitivity of HIV- 1 and SIVagm to NNRTIs. PMID- 11205101 TI - Mutational analysis of the NIa protease from pepper vein banding potyvirus. AB - The nuclear inclusion protein a (NIa) protease plays an important role in the life cycle of potyviruses by processing the viral polyprotein into functional proteins. For functional characterization, the NIa protease from Pepper vein banding potyvir s (PVBV) was overexpressed in Escherichia coli and purified. Using a recombinant polyprotein substrate containing the nuclear inclusion protein b (NIb)-coat protein (CP) cleavage site, a trans-cleavage assay was developed for the NIa protease. The polyprotein substrate also possessed the cleavage site between NIa and NIb, in addition to the NIb-CP site. However, no trans-cleavage by the NIa protease between NIa and NIb was detected indicating that the cleavage between NIa and NIb under natural conditions would be by a cis cleavage reaction. Site-specific mutations of the conserved residues D81, D90, C110, T146, C151 and H167 were performed to investigate their roles in the catalytic process of the protease. Such an analysis has revealed that D81 and C151 constitute two of the catalytic triad residues in the NIa protease, D90 and C110 are not essential for catalysis, and T146 and H167 are probably involved in binding to Gln at the P1 position of the substrate. PMID- 11205102 TI - Molecular characterization of Hop latent virus and phylogenetic relationships among viruses closely related to carlaviruses. AB - The complete nucleotide sequence of the hop latent virus (HpLV) genome was determined. The viral RNA genome is 8,612 nucleotides long, excluding the poly(A) tail, and contains six open reading frames (ORFs), which encode putative proteins of 224-kDa (ORF 1), 25-kDa (ORF 2), 11-kDa (ORF 3), 7-kDa (ORF 4), 34-kDa (ORF 5), and 12-kDa (ORF 6). ORF 5 encodes the coat protein as demonstrated by N terminal sequencing of three proteolytic peptides derived from the virus particle. The genome organization of HpLV is similar to that of other species in the genus Carlavirus, and the overall sequence of HpLV is more similar to that of Potato virus M than to sequences of other carlaviruses reported to date. The amino acid sequences of the putative methyltransferase, RNA helicase, and RNA dependent RNA polymerase encoded in ORF 1 and an 'accessory' helicase encoded in ORF 2 of the HpLV genome were compared with those of viruses in the 'tymo' lineage: the genera Carlavirus, Potexvirus, Allexivirus, Foveavirus, Trichovirus, Capillovirus, Vitivirus, and Tymovirus. The phylogenetic relationships among the viruses in these genera are discussed. This is the first molecular characterization of a carlavirus infecting hop plants. PMID- 11205104 TI - Genomic organization of Helicoverpa armigera single-nucleocapsid nucleopolyhedrovirus. AB - The genome organization of the Helicoverpa armigera single-nucleocapsid nucleopolyhedrovirus (HearNPV) was investigated and compared to that of other baculoviruses. A detailed physical map was constructed for the restriction enzymes BamHI, BglII, EcoRI, HindIII, KpnI, PstI, SacI and XhoI. The 130.1 kilobase pairs (kb) long viral genome was cloned as restriction fragments into a plasmid library, which covered 97.5% of the viral genome. From this plasmid library about 45 kb of dispersed sequence information was generated. Fifty-three putative open reading frames (ORFs) with homology to ORFs of other baculoviruses were identified and their location on the genome of HearNPV was determined. The arrangement of the ORFs along the HearNPV genome is significantly different from the multiple-nucleocapsid NPVs, AcMNPV, BmNPV and OpMNPV, which have a highly collinear genome, and the granulovirus XcGV. In contrast the genomes of HearNPV and SeMNPV are highly collinear. This close relatedness between an MNPV and an SNPV is supported by the phylogeny of specific genes of these two viruses and suggests that the morphotype (S or M) is only a taxonomic and not a phylogenetic denominator. The data presented here also give further support to the view that the gene distribution along baculovirus genomes can be used as a character to describe baculovirus relatedness independent of gene phylogeny. Five homologous regions (hrs) were located on the genome of HearNPV. This is also the first report of the existence of hrs in SNPVs and this observation suggests that hrs are a common feature of baculovirus genomes. PMID- 11205103 TI - Studies on feline CD8+ T cell non-cytolytic anti-feline immunodeficiency virus (FIV) activity. AB - CD8+ T cells in FIV-infected cats inhibit feline immunodeficiency virus (FIV) replication by producing a soluble factor(s). In the present study, four SPF cats were experimentally infected with FIV. The period during which the anti-FIV activity of CD8+ T cells became detectable was investigated, and the presence or absence of this activity in the lymph nodes and spleen was examined. Furthermore, we investigated which step(s) of the FIV replication cycle are affected by this antiviral activity. This antiviral activity became detectable five weeks after FIV infection in early cases, and it was simultaneous with or one week after the induction of humoral immunity. All cats having CD8+ T cells with anti-FIV activity in the peripheral blood also possessed CD8+ T cells with anti-FIV activity in the lymph nodes. In contrast, CD8+ T cells from the spleens of some, but not all cats showed anti-FIV activity. CD8+ T cell-depleted peripheral blood mononuclear cells were cultured and reconstituted with CD8+ T cells on day 12 of culture after confirming FIV replication. The number of FIV proviral DNA copies in the cells did not change, but the amount of FIV p24 antigen production in the culture supernatant and the number of FIV mRNA copies in the cells decreased. These findings suggested that CD8+ T cell anti-FIV activity acts at the level of FIV mRNA synthesis from the FIV proviral DNA, inhibiting FIV replication by a non cytolytic mechanism. PMID- 11205105 TI - Development of a plant-derived subunit vaccine candidate against hepatitis C virus. AB - Hepatitis C virus (HCV) is a major cause of acute and chronic hepatitis with over 180 million cases worldwide. Vaccine development for HCV has been difficult. Presently, the virus cannot be grown in tissue culture and there is no vaccine or effective therapy against this virus. In this research, we describe the development of an experimental plant-derived subunit vaccine against HCV. A tobamoviral vector was engineered to encode a consensus sequence of hypervariable region 1 (HVR1), a potential neutralizing epitope of HCV, genetically fused to the C-terminal of the B subunit of cholera toxin (CTB). This epitope was selected from among the amino acid sequences of HVR1 "mimotopes" previously derived by phage display technology. The nucleotide sequence encoding this epitope was designed utilizing optimal plant codons. This mimotope is capable of inducing cross-neutralizing antibodies against different variants of the virus. Plants infected with recombinant tobacco mosaic virus (TMV) engineered to express the HVR1/CTB chimeric protein, contained intact TMV particles and produced the HVR1 consensus peptide fused to the functionally active, pentameric B subunit of cholera toxin. Plant-derived HVR1/CTB reacted with HVR1-specific monoclonal antibodies and immune sera from individuals infected with virus from four of the major genotypes of HCV. Intranasal immunization of mice with a crude plant extract containing the recombinant HVR1/CTB protein elicited both anti-CTB serum antibody and anti-HVR1 serum antibody which specifically bound to HCV virus-like particles. Using plant-virus transient expression to produce this unique chimeric antigen will facilitate the development and production of an experimental HCV vaccine. A plant-derived recombinant HCV vaccine can potentially reduce expenses normally associated with production and delivery of conventional vaccines. PMID- 11205106 TI - Nucleotide sequences and mutations of the 5'-nontranslated region (5'NTR) of natural isolates of an epidemic echovirus 11' (prime). AB - An echovirus 11' (prime) virus caused an epidemic in Hungary in 1989. The leading clinical form of the diseases was myocarditis. Hemorrhagic hepatitis syndroms were also caused, however, with lethal outcome in 13 newborn babies. Altogether 386 children suffered from registered clinical disease. No accumulation of serous meningitis cases and intrauterine death were observed during the epidemic, and the monovalent oral poliovirus vaccination campaign has prevented the further circulation of the virus. The 5'-nontranslated region (5'-NTR) of 12 natural isolates were sequenced (nucleotides: 260-577). The 5'-NTR was found to be different from that of the prototype Gregory strain (X80059) of EV11 (less than 90% identity), but related to the swine vesicular disease virus (D16364) SVDV and EV9 (X92886) as indicated by the best fitting dendogram. The examination of the variable nucleotides in the internal ribosomal entry site (IRES) revealed, that the nucleotide sequence of a region of the epidemic 5'-NTR was identical to that of coxsackievirus B2. Five of the epidemic isolates were found to carry mutations. Seven EV11' IRES elements possessed identical sequences indicating, that the virus has evolved before its arrival to Hungary. The comparative examination of the suboptimal secondary structures revealed, that no one of the mutations affected the secondary structure of stem-loop structures IV and V in the IRES elements. Although it has been shown previously, that the echovirus group is genetically coherent and related to coxsackie B viruses the sequence differences in the epidemic isolates resulted in profound modification of the central stem (residues 477-529) of stem-loop structure No.V known to be affecting neurovirulence of polioviruses. Two alternate cloverleaf (stem-loop) structures were also recognised (nucleotides 376 to 460 and 540 to 565) which seem to mask both regions of the IRES element complementary to the 3'-end of the 18 S rRNA (460 to 466 and 561 to 570), thus probably diminishing initiation of translation. The possible biological importance of the alternative cloverleaf structures is supported by the fact that neither the 17 variable nucleotides nor the two mutations of epidemic isolates within the regions seem to modify the predicted alternative secondary structures in EV11, SVDV and CBV1-4. PMID- 11205107 TI - Immune responses and cytokine induction in the development of severe hepatitis during acute infections with murine cytomegalovirus. AB - Salivary gland-derived murine cytomegalovirus (SGV) infections of mice have been widely used as models of human cytomegalovirus infections and in the study of CMV biology. Still, many aspects of SGV pathogenesis are not clearly defined. Fatal and non-fatal SGV infections were investigated to characterize pathogenetic correlates of mortality and to assess the role of the immune response in disease progression. Suppression of immune responses was observed in both lethal and sublethal infections. Depletion of immune cell populations in spleen, however, correlated with severe CMV-induced hepatitis and mortality. In addition, T cell depletion studies indicated a requirement for this immune cell subset in control of liver damage and survival of infected mice. Examination of cytokine responses revealed a previously undescribed shock-like syndrome in lethally-infected mice characterized by high levels of tumor necrosis factor alpha and interferon gamma. Furthermore, the sites of tumor necrosis factor alpha gene induction did not strictly correlate with either viral load or the sites of tissue damage during infection. Taken together, these findings define the pathogenetic progression of disease as it relates to disease outcome and suggests that organ-specific differences in cytokine induction play a significant role in the late stages of acute lethal MCMV infections. PMID- 11205108 TI - Equine herpesvirus 9 induced lethal encephalomyelitis in experimentally infected goats. AB - The pathogenicity of a new neurotropic equine herpesvirus 9 (EHV-9) formerly designated gazelle herpesvirus 1 was evaluated using the goat as a representative of domesticated ruminants. Two goats inoculated intranasally with EHV-9 showed salivation, teeth grinding and other neurological disorders on day 8 post inoculation. One goat died 30 min after the onset of clinical signs and the other was sacrificed 3 h after the sudden onset of teeth grinding and foamy salivation. EHV-9 was recovered from peripheral white blood cells, the olfactory bulbs and brain, nasal swabs, concha, and lungs. Neuropathological lesions were located in the olfactory bulbs, cerebrum, midbrain and medulla oblongata with degeneration and necrosis of neurons, rarefaction, perivascular infiltration of mononuclear cells, and nodal glial reaction. EHV-9 antigen was detected in neurons in the lesions. These findings indicated that EHV-9 is highly pathogenic with high neurotropism for goats. PMID- 11205109 TI - An Ophiovirus isolated from lettuce with big-vein symptoms. AB - Big-vein is a widespread and damaging disease of lettuce, transmitted through soil by the chytrid fungus Olpidium brassicae, and generally supposed to be caused by Lettuce big-vein virus (LBVV; genus Varicosavirus). This virus is reported to have rigid rod-shaped particles, a divided double-stranded RNA genome, and one capsid protein of 48 kD, but has not been isolated or rigorously shown to cause the disease. We provide evidence that a totally different virus, here named Mirafiori lettuce virus (MiLV), is also very frequently associated with lettuce showing big-vein symptoms. MiLV was mechanically transmissible from lettuce to Chenopodium quinoa and to several other herbaceous test plants. The virus was partially purified, and an antiserum prepared, which did not react with LBVV particles in decoration tests. As reported for LBVV, MiLV was labile, soil transmitted and had a single capsid protein of 48 kD, but the particles morphologically resembled those of ophioviruses, and like these, MiLV had a genome of three RNA segments approximately 8.5, 1.9 and 1.7 kb in size. MiLV preparations reacted strongly in Western blots and in ISEM with antiserum to Tulip mild mottle mosaic virus, an ophiovirus from Japan also apparently Olpidium transmitted. They reacted weakly but clearly in Western blots with antiserum to Ranunculus white mottle virus, another ophiovirus. When lettuce seedlings were mechanically inoculated with crude or partially purified extracts from MiLV infected test plants, many became systemically infected with MiLV and some developed big-vein symptoms. Such plants did not react in ELISA using an LBVV antiserum or an antiserum to tobacco stunt virus, and varicosavirus-like particles were never seen in them in the EM after negative staining. We conclude that MiLV is a hitherto undescribed virus assignable to the genus Ophiovirus. The cause or causes of lettuce big-vein disease and the properties of LBVV may need to be re-evaluated in light of our results. PMID- 11205110 TI - Genetic composition and complexity of virus populations at tungro-endemic and outbreak rice sites. AB - We have recently demonstrated the geographic isolation of rice tungro bacilliform virus (RTBV) populations in the tungro-endemic provinces of Isabela and North Cotabato, Philippines. In this study, we examined the genetic structure of the virus populations at the tungro-outbreak sites of Lanao del Norte, a province adjacent to North Cotabato. We also analyzed the virus populations at the tungro endemic sites of Subang, Indonesia, and Dien Khanh, Vietnam. Total DNA extracts from 274 isolates were digested with EcoRV restriction enzyme and hybridized with a full-length probe of RTBV. In the total population, 22 EcoRV-restricted genome profiles (genotypes) were identified. Although overlapping genotypes could be observed, the outbreak sites of Lanao del Norte had a genotype combination distinct from that of Subang or Dien Khanh but a genotype combination similar to that identified earlier from North Cotabato, the adjacent endemic province. Sequence analysis of the intergenic region and part of the ORF1 RTBV genome from randomly selected genotypes confirms the geographic clustering of RTBV genotypes and, combined with restriction analysis, the results suggest a fragmented spatial distribution of RTBV local populations in the three countries. Because RTBV depends on rice tungro spherical virus (RTSV) for transmission, the population dynamics of both tungro viruses were then examined at the endemic and outbreak sites within the Philippines. The RTBV genotypes and the coat protein RTSV genotypes were used as indicators for virus diversity. A shift in population structure of both viruses was observed at the outbreak sites with a reduced RTBV but increased RTSV gene diversity. PMID- 11205111 TI - Evidence for two distinct subgroups of alfalfa mosaic virus (AMV) from france and italy and their relationships with other AMV strains Brief report. AB - The nucleotide sequence of the putative coat protein open reading frame of seven previously uncharacterized AMV strains from Italy and France was determined and aligned with comparable sequences of other AMV strains (425 L, 425 M, YSMV, S, VRU, 15/64 and Da). The data set of AMV sequences was used to determine phylogenetic relationships by both a stochastic (stationary Markov model) and a deterministic method (maximum-parsimony) of analysis. The topology of the trees obtained with the two methods was essentially the same showing that all AMV strains clustered in two monophyletic groups. Close clustering of Italian strains in subgroup I and of French strains in subgroup II seems to suggests the effect of geographic distinctiveness of evolutionary dynamics of these AMV strains. This separation did not correlate with differences in host range or symptoms (necrotic or non necrotic) induced in tomato but rather it reflected variations in the amino acid sequence of their CP, which might be related to structural properties of virus particles. A simple and rapid procedure based on the reverse transcriptase-polymerase chain reaction (RT-PCR) followed by ezymatic digestion (RFLP) was developed to identify and classify AMV isolates into the two subgroups. The method applied to a number of other AMV isolates from Italy and France supported their division in two distinct subgroups. This RT-PCR RFLP method may be useful way to investigate the dynamics of AMV populations in nature. PMID- 11205112 TI - Amplification and analysis of DNA flanking known sequences of a novel herpesvirus from green turtles with fibropapilloma Brief report. AB - A 1,632-bp fragment, flanking the original 483-bp region of the DNA polymerase gene of a novel herpesvirus found in tissues of green turtles (Chelonia mydas) with fibropapilloma, was amplified from the circularized EcoRI-cut DNA extracted from tumor tissues by inverse PCR. The resultant 2,019-bp partial sequence of the DNA polymerase gene of the newfound herpesvirus, including the original 483-bp region, showed a high degree of homology at both the nucleotide and amino acid levels with that of other human and animal herpesviruses. Phylogenetic analysis confirmed that this novel herpesvirus belonged to the Alphaherpesvirinae subfamily. PMID- 11205113 TI - Characterisation of IE and UL5 gene products of equine herpesvirus 1 using DNA inoculation of mice. AB - The equine herpesvirus 1 (EHV-1) strain HVS25A regulatory genes IE and UL5, encoding homologues of herpes simplex virus 1 (HSV-1) ICP4 and ICP27 respectively, were cloned into a eukaryotic expression vector and the DNA injected intramuscularly into mice. Antibodies produced in this way detected the IE or UL5 gene products as diffuse material in nuclei of RK13 cells transfected with the individual genes but as discrete punctate or large aggregates in RK13 cells infected with EHV-1. Western blotting on EHV-1 infected RK13 cells showed multiple IE products of 120-200 kDa and a UL5 product of 52 kDa. Inoculation with plasmids expressing EHV-1 IE or UL5 provided limited protection against EHV-1 challenge in mice as determined by increased virus clearance from lungs on day 2 post-challenge and a reduction in severity of lung histopathology. However, this protection was relatively weak compared with that provided by inoculation of DNA encoding EHV-1 glycoprotein D (gD), possibly reflecting the importance of neutralising antibody in this model. PMID- 11205114 TI - Influenza chemotherapy: a review of the present state of art and of new drugs in development. AB - Influenza is worldwide one of the deadliest infectious diseases. Lethal influenza mutants can unpredictably arise, as in the 1918 pandemic, or in the 1997 Hong Kong influenza outbreak. Vaccines are today the only protective prophylactic agents, and development of potent new anti-influenza drugs of therapeutic effectiveness appears urgent. It is the aim of the present review, to summarize and discuss the different investigational approaches to this goal. In Medline- and several internet virology database-searches, numerous citations were compiled, and selected according to their relevance to the different topics discussed. The antiviral agents are classified according to their target in the viral replication cycle: proteolytic activation of haemagglutinin, attachment of the virus to specific cell-surface receptors, endocytosis and fusion with the endosomal membrane, uncoating of the nucleocapsid, multiplication, i.e. synthesis of viral RNA and mRNA, and release of the new virus generation from the host cell surface. Potential drugs, directed towards each of these replication steps are described with respect to their mechanism of action, antiviral activity, toxic side effects and induction of resistance. The most promising candidates for safe and potent new influenza drugs, are antiviral agents, directed towards a virus specific, well conserved target, such as inhibitors of virus-cell fusion, inhibitors of RNA transcriptase and endonuclease, and inhibitors of neuraminidase. It can be hoped that in the near future potent and therapeutically effective anti-influenza drugs will be available. PMID- 11205115 TI - Molecular characterization of a new potyvirus infecting sunflower. AB - We have sequenced 1873 nucleotides from the 3'-end region of a sunflower potyvirus genome including the 3'-NIb protein coding region (813 nucleotides), the entire coat protein coding region (807 nucleotides) and 3'-NCR (253 nucleotides), excluding the poly (A) tail. Amino acids identity of the whole CP between the sunflower virus and Potyvirus members ranged from 49.5% (SCMV) to 81.5% (PVY-NsNr), and the core ranged from 55% (TVMV) to 87% (PVY-NsNr; PepMoV). The 3'-NCR nucleotides showed 38.7% homology to PeSMV and 61% to PepMoV-C. The sequence of 3' end region and analysis of phylogenetic relationships suggest this sunflower virus could belong to PVY subgroup and the name of "sunflower chlorotic mottle virus" (SuCMoV) is proposed. This is the first report on the partial nucleotide sequence of a potyvirus infecting sunflower. PMID- 11205116 TI - Latent herpes simplex virus-1 infection in SCID mice transferred with immune CD4+T cells: a new model for latency. AB - In C.B-17 severe combined immunodeficiency (SCID) mice, corneal challenge with herpes simplex virus-1 (HSV-1) KOS strain usually leads to fatal encephalitis. With the transfer of T cells from immunized BALB/c mice, these SCID mice developed a latent HSV-1 infection. In order to determine the responsible T cell subset, fractionated immune T cells were transferred. Those SCID mice transferred with immune CD4+T cell-enriched fraction developed latent HSV-1 infection in their trigeminal ganglia. Their splenocytes had an increased percentage of CD4+T cells and showed a proliferative response against HSV-1. The transfer of CD8+T cells increased survival in the acute infection, but their engraftment seemed less needed for latency than that of CD4+T cells. Mice that received immune serum survived without developing latent HSV-1 infection. Some latently infected SCID mice had anti-HSV antibodies while others did not, indicating that the engraftment of antibody-producing B cells was not required for latency. Thus, immune CD4+T cells were important for the survival of SCID mice with latent HSV-1 infection. This animal model should be useful for investigation of latency/reactivation of HSV-1. PMID- 11205117 TI - Sequence variants and functional analysis of human papillomavirus type 16 E5 gene in clinical specimens. AB - Previously, we found that the E5 protein can be expressed in HPV-16 infected precancerous lesions and cervical cancer. In this study, we investigated the presence of sequence variants of E5 in HPV-16 infected tissues. Toward this end, we amplified the E5 gene by polymerase chain reaction from 29 HPV-16 infected tissues including eight normal tissues, seven high grade neoplastic tissues (high grade squamous intraepithelial lesions (HSIL) and 14 cervical cancer tissues. Sequence analysis demonstrated that there were three mutational hot spots at positions 3979, 4042, and 4077 of the HPV-16 DNA; these and other mutations resulted in six variants in the E5 sequence. This resulted in four E5 protein mutants, named WTE5 [wild type E5 protein], 14E5, 21E5 and 56E5. Functional analysis of these four mutant proteins revealed that the transforming activities of 14E5, 21E5 and 56E5 were 0.95, 0.59, and 0.89 fold of WTE5, respectively. Although E5 was expressed in all of the HSIL and cervical cancer tissues, but in only one of the eight normal tissues tested, only WT E5 protein was found in HSIL while in cervical cancer tissues both WT and mutant E5 proteins were detected. Since these E5 proteins exhibited the same in vitro transforming activity, these data suggest that expression of E5 is important in development and progression toward malignancy but mutation of E5 does not affect the transformation process. PMID- 11205118 TI - Development and evaluation of a complementation-dependent gene delivery system based on cucumber mosaic virus. AB - To engineer cucumber mosaic virus (CMV-Ix) into a gene vector, genome component RNA 3 of the virus was modified and split into two sub-components, RNA 3A and RNA 3B. In RNA 3A, the open reading frame of the movement protein (MP) was replaced by a reporter gene encoding the green fluorescent protein (GFP), to monitor virus replication and movement. In RNA 3B, the coat protein (CP) gene was eliminated and a multiple cloning site (MCS) was created for foreign gene insertion. Each sub-component alone is defective and relies on its companion sub-component to restore full RNA 3 function. The vector system was evaluated for its ability to deliver and express the bacterial beta-glucuronidase (GUS) gene and a modified bean yellow mosaic virus coat protein (BYMV-CP) gene in Nicotiana benthamiana plants. Results showed that the engineered virus was able to move from cell to cell in the inoculated leaf and enter the minor veins of the inoculated leaf. Foreign gene expression was detected in the inoculated leaves. However, intermolecular recombination between RNA 3A and 3B occurred frequently, preventing efficient systemic expression of the foreign gene(s). Modifications and further evaluations are being undertaken to improve the gene delivery system. PMID- 11205119 TI - Full-length sequence of a Canadian porcine reproductive and respiratory syndrome virus (PRRSV) isolate. AB - Presently, one of the most economically important pathogens affecting swine is the porcine reproductive and respiratory syndrome virus (PRRSV). This virus is prevalent in herds throughout the world and continues to pose a significant threat as newer and more virulent disease phenotypes emerge. In this report we describe the full-length nucleotide sequence of a Canadian PRRSV isolate, designated PA8. A consecutive sequence of 15,411 nucleotides was obtained from a set of overlapping cDNA clones. In order to determine the extent of genetic variation among isolates recovered from swine in Canada and the US, as well as to understand the molecular mechanisms governing the evolution of PRRSV, the full length sequence of PA8 was compared with that of two US isolates, VR2332 and 16244B. The genomic sequence of PA8 shared 98.2% and 99.2% identity with 16244B and VR2332, respectively. The untranslated regions (UTR) at the 5' and 3' ends of the genome were very well conserved. Notable exceptions include an eight nucleotide difference at the 5' end of the 5' UTR of VR2332 relative to PA8 and 16244B and a two nucleotide difference in the 3' UTR of PA8 relative to VR2332 and 16244B. In contrast to PA8 and VR2332, 16244B possessed two nucleotide differences within the RNA pseudoknot structure of the ribosomal frameshift region between open reading frame (ORF)1a and ORF1b. Amino acid differences were distributed throughout the genome, however they appeared to be most extensive in Nsp1beta and ORF5 of the nonstructural and structural coding regions, respectively, suggesting that the evolutionary pressure to conserve these viral genes is somewhat lower. PMID- 11205120 TI - Zucchini green mottle mosaic virus is a new tobamovirus; comparison of its coat protein gene with that of kyuri green mottle mosaic virus. AB - A novel virus we call zucchini green mottle mosaic virus (ZGMMV) was isolated from zucchini squash and its properties were determined. The size and shape of its virions, and other properties suggest that the virus is a tobamovirus. The coat protein (CP) genes of ZGMMV and kyuri green mottle mosaic virus (KGMMV), which also infects zucchini squash plants, were cloned and their nucleotides sequences were determined. The CP genes of ZGMMV and KGMMV are composed of 161 amino acid residues, and they share 77.6% amino acid identity. Western blot analysis showed that the two viruses are serologically related but not identical. Comparison of the sequences with those of sixteen other tobamoviruses revealed that the two viruses had much higher identity to cucumber green mottle mosaic virus (CGMMV), another tobamovirus infectious to cucurbit plants, than other tobamoviruses. The nucleotide and amino acid sequences of ZGMMV were from 29.5 to 78.4% and from 29.3 to 77.6% identical, respectively, to those of other tobamoviruses. The predicted virion assembly origins of the two tobamoviruses were located in the CP region of the genomic RNAs, and the predicted secondary structures were more similar to that of CGMMV than those of other tobamoviruses. The seventeen tobamo-viruses could be classified into three main subgroups based on the phylogenetic tree analysis on the CP gene, and ZGMMV and KGMMV formed a third subgroup together with CGMMV and sunn-hemp mosaic virus (SHMV). These results show that ZGMMV is a previously unknown member of the Tobamovirus genus. PMID- 11205121 TI - Antibody responses to respiratory coronavirus infections of cattle during shipping fever pathogenesis. AB - Antibody responses against respiratory bovine coronavirus (RBCV) infections were monitored in cattle from the onset of a naturally occurring severe shipping fever (SF) epizootic to complete recovery of affected cattle or fatal outcomes. The infection with RBCV was detected in nasal secretions of 86 cattle, and 81 of them developed acute respiratory tract disease, including fatal pneumonia. Cattle nasally shedding RBCV at the beginning of the epizootic experienced characteristic primary immune responses with specific antibodies for hemagglutinin-esterase (HE) and spike (S) glycoproteins. Virus shedding in nasal secretions of the majority of the cattle ceased between days 7 and 14 with the appearance of HE- and S-specific antibodies. Nasal samples and lung tissues from 9 of the 10 fatal cases had high titers of RBCV, but these cattle had only IgM responses to RBCV infections. Cattle remaining negative in RBCV isolation tests entered this epizootic with antibodies against HE and S. Protection against respiratory tract disease was apparently associated with high level of opsonic and virus-neutralizing IgG2. The HE and S glycoproteins were recognized earliest by the bovine immune system while the N protein induced antibody responses during the later stage of initial infection and the early stage of reinfection. The membrane (M) glycoprotein was the least immunogenic of the major viral structural proteins. PMID- 11205122 TI - Characterization of four isolates of Bombyx mori nucleopolyhedrovirus. AB - Bombyx mori nucleopolyhedroviruses (BmNPVs), isolated from a sericultural Korean farm, were purified and characterized by their DNA restriction pattern, virus replication, polyhedra production and gene structures. The EcoR I and Sal I fragments showed similar overall patterns with minor difference but distinguishable patterns in each isolate. There was no significant difference in the virus replication pattern, yield of total polyhedra production and polyhedra morphology, but the yield of released polyhedra by BmNPV-K1 in Bm5 cells was 2 to 5 times higher than that of other isolates. In comparative studies of p10 gene, BmNPV-K1 and K3 had same structure and they encoded a protein consisting of 94 amino acids. Although BmNPV-K2 encoded the same length of amino acids with BmNPV K1 and K3, it had different structure, and BmNPV-K4 had the p10 gene encoding 70 amino acids. PMID- 11205123 TI - Characterization of a bovine herpesvirus type 4 isolated from the spinal cord of a cow with astasia. AB - A bovine herpesvirus (BHV) strain designated B11-41, was recently isolated from the spinal cord of a cow with astasia. By BHV type specific polymerase chain reaction (PCR), a BHV-4 specific fragment was amplified from the DNA of strain B11-41. The nucleotide sequence of the PCR product revealed high homologies (98.4% and 99.8%) with those of two BHV-4 strains (Movar 33/63 and 86-068). The BamHI restriction endonuclease cleavage patterns of the B11-41 were more similar to those of BHV-4 than those of other types of BHV. BHV-4 is divided into two groups, European and American. The EcoRI, and BamHI, and HindIII restriction endonuclease analysis demonstrated that strain B11-41 was closely related to the American type of BHV-4. It was concluded that B11-41 was identified as a BHV-4 that belongs to the American group. Additionally, the results of this study may indicate that the nervous system is one of the sites of viral latency in natural infection. PMID- 11205124 TI - EHV-1 glycoprotein D (EHV-1 gD) is required for virus entry and cell-cell fusion, and an EHV-1 gD deletion mutant induces a protective immune response in mice. AB - Insertional mutagenesis was used to construct an equine herpesvirus 1 (EHV-1) mutant in which the open reading frame for glycoprotein D was replaced by a lacZ cassette. This gD deletion mutant (delta gD EHV-1) was unable to infect normally permissive RK cells in culture, but could be propagated in an EHV-1 gD-expressing cell line (RK/gD). Phenotypically complemented delta gD EHV-1 was able to infect RK cells, but did not spread to form syncytial plaques as seen with wild type EHV 1 or with delta gD EHV-1 infection of RK/gD cell cultures. Therefore EHV-1 gD is required for virus entry and for cell-cell fusion. The phenotypically complemented delta gD EHV-1 had very low pathogenicity in a mouse model of EHV-1 respiratory disease, compared to a fully replication-competent EHV-1 reporter virus (lacZ62/63 EHV-1). Intranasal or intramuscular inoculation of mice with delta gD EHV-1 induced protective immune responses that were similar to those elicited in mice inoculated with lacZ62/63 EHV-1 and greater than those following inoculation with UV-inactivated virus. PMID- 11205125 TI - Altered local and systemic spread of movement deficient virus in transgenic tobacco plants expressing the cucumber mosaic virus 3a protein. AB - The 3a protein encoded by RNA 3 of cucumber mosaic virus has been identified as the viral cell-to-cell movement protein. The constitutive expression in transgenic tobacco plants of 3a protein from a subgroup I strain was able to complement in trans the short distance movement of a 3a defective CMV mutant belonging to a different taxonomic subgroup. This ability was dependent upon the accumulation levels of the 3a protein in transgenic tobacco plants. However, an initial delay in viral accumulation and spread of the defective virus as compared to the wild type virus was determined in complementation tests. Furthermore, a reduction in disease symptoms as well as a different pattern of systemic viral distribution from those of the wild type virus was detected. These results show that the early events in viral infection affect the long distance spread of the virus. Finally, the wild type virus moved faster in the 3a protein-expressing plants than in control plants, thus indicating that the constitutive expression of the 3a protein favours long-distance viral spread. PMID- 11205126 TI - Human rotavirus HCR3 possesses a genomic RNA constellation indistinguishable from that of feline and canine rotaviruses. AB - Infection and spread of group A rotaviruses under natural conditions are mostly limited to one animal host species. However, rare molecular evidence exists for interspecies transmission by whole virions of animal rotaviruses to humans. Human rotavirus strain HCR3, which was isolated in 1984 from a healthy infant in Philadelphia, U.S.A. was shown by RNA-RNA hybridization to form 11 hybrid bands with feline rotavirus strain FRV64 and canine rotavirus strains CU-1 and K9, but not with rotaviruses commonly found in humans. Thus, HCR3 was concluded to be originally a rotavirus circulating in cats and dogs and accidental interspecies transmission by whole virions to humans was likely to have occurred in the past. PMID- 11205127 TI - Murine gammaherpesvirus M11 gene product inhibits apoptosis and is expressed during virus persistence. AB - The murine gammaherpesvirus (MHV-68) M11 gene encodes a protein with BH1 domain homology to Bcl-2. We found that the M11 gene product (MHVBcl-2) protected murine epithelial cells from TNF-alpha induced apoptosis. M11 was transcribed during early lytic infection in vitro. During early infection of mice, M11 message was detected in spleen and lung along with lytic cycle messages. During persistence, lytic cycle gene expression was undetectable but M11 RNA was still present. This suggests that MHVBcl-2 promotes virus survival by protecting not only productively infected but also persistently infected cells from apoptotic death. PMID- 11205128 TI - Experimental infection of colostrum deprived piglets with porcine circovirus 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) potentiates PCV2 replication. AB - Experimental infection of colostrum-deprived (CD) pigs with a combined inoculum of porcine circovirus 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) potentiated the replication and distribution of PCV2 virus, when compared with pigs inoculated with PCV2 alone. The replication and distribution of PRRSV in dually infected pigs was not enhanced, when compared to pigs inoculated with PRRSV alone. The mechanisms involved in the potentiation of PCV2 replication in PCV2/PRRSV and PCV2/porcine parvovirus (PPV) dually infected pigs may relate to the fact that monocyte/macrophage cell types are common targets of these 3 viruses. PMID- 11205129 TI - Improving permissive infection of human cytomegalovirus in cell culture. AB - Changes in human cytomegalovirus (HCMV) titre occurring under different conditions were studied using plaque assay. No significant change in titre was found using primary embryonic fibroblasts or primary foreskin fibroblasts, or with the addition of dexamethasone to the medium. Significant increases in titre were found when standard cultures were pre-incubated in medium containing DEAE dextran and/or calcium chloride. However, DEAE-dextran and/or calcium chloride had no significant effect on HCMV detection using the shell vial assay, possibly because enhancement affects permissive infection, but not surface expression of viral antigens. DEAE-dextran and calcium chloride can be included in the medium of standard cultures as a means of obtaining higher titres of HCMV, and are particularly useful for isolates that are difficult to culture. PMID- 11205130 TI - The post-Loeffler era: contribution of German virologists. PMID- 11205131 TI - XV Courses of the Italian Neurological Society. Milan, September 23-27, 2000. Abstracts. PMID- 11205132 TI - The L-DOPA story revisited. Further surprises to be expected? AB - L-DOPA therapy for Parkinson's disease is one of the major achievements of twentieth century neurology; Parkinson's disease was the first in which specific neurochemical deficits in defined brain regions were identified, and thus for which a rational, chemical therapy could be developed, ushering in the era of clinical neurochemistry. The contributions of Birkmayer and Hornykiewicz (Vienna), Barbeau and Sourkes (Montreal) and of Cotzias (New York) to this story are well-known. Almost completely forgotten, on the other hand, is a paper presented by the Japanese neurologist Isamu Sano in 1960 which reported what is probably the first attempt to treat Parkinson's disease patients with DOPA. This is all the more remarkable as the author was also responsible for one of the key papers which led to the use of DOPA in Parkinson's disease by other workers. Despite the negative outcome of his experience with L-DOPA, Sano deserves to be remembered as one of the pioneers in catecholamine research, having been the first to map dopamine levels in the human brain, and identified the reduction of dopamine levels in the substantia nigra and striatum in Parkinson's disease. PMID- 11205133 TI - Importance of familial Parkinson's disease and parkinsonism to the understanding of nigral degeneration in sporadic Parkinson's disease. AB - We review here familial Parkinson's disease (PD) from clinical as well as molecular genetic aspects. The contribution of genetic factors to the pathogenesis of PD is supported by the demonstration of the high concordance in twins, increased risk among relatives of PD patients in case control and family studies, and the existence of familial PD and parkinsonism based on single gene defects. Recently, several genes have been mapped and/or identified in patients with familial PD. Alpha-synuclein is involved in a rare dominant form of familial PD with dopa responsive parkinsonian features and Lewy body positive pathology. In contrast, parkin is responsible for autosomal recessive form of early-onset PD with Lewy body-negative pathology. This form is identified world-wide among patients with young-onset PD. Furthermore, ubiquitin carboxy terminal hydrolase L1 gene is responsible for an autosomal dominant form of typical PD, although only a single family has so far been identified with a mutation of this gene, and tau has been identified as a causative gene for frontotemporal dementia and parkinsonism. In addition, five other chromosome loci have been identified to be linked to familial PD or dystonia-parkinsonism. The presence of different loci or different causative genes indicates that PD is not a single entity but a highly heterogeneous. Identification and elucidation of the causative genes should enhance our understanding of the pathogenesis of sporadic PD. PMID- 11205135 TI - Monitoring neuroprotection and restorative therapies in Parkinson's disease with PET. AB - In this article the role of functional imaging (PET and SPECT) as a surrogate marker for following the progression of Parkinson's disease (PD) is discussed. The potential value of PET and SPECT for assessing the efficacy of putative neuroprotective agents in PD is considered and a review of 18F-dopa PET findings in transplantation trials involving implantation of human and procine fetal mesencephalic tissue is presented. It is concluded that functional imaging provides a valuable adjunct to clinical assessment when judging the efficacy of neuroprotective and restorative approaches to PD. PMID- 11205134 TI - cDNA microarray to study gene expression of dopaminergic neurodegeneration and neuroprotection in MPTP and 6-hydroxydopamine models: implications for idiopathic Parkinson's disease. AB - cDNA microarray membranes comprising 1,200 different gene fragments have been employed to identify gene expression profile in MPTP-induced nigro striatal dopamine neurodegeneration and its protection with Rapomorphine. Both MPTP (N methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and R-apomorphine (R-APO) induced alterations in specific patterns of gene expression. MPTP altered the expression of 49 different genes involved in oxidative stress (oxidative stress-induced protein A 170, cytochrome P450 1A1 and Osp94), inflammation (cytotoxic cytokines, eg: IL-1, IL-6, TNF-alpha), protective cytokines (IL-10), glutamate receptors (NMDA but not AMPA receptors), neurotrophic factors (GDNF, EGF), nitric oxide synthase and transferrin receptor, as determined by microarray membrane hybridization. Furthermore, an additional cascade of further, yet undefined events, also occurred (cell cycle regulators and signal transduction factors), that might act in parallel to oxidative stress (OS) and inflammation, to converge eventually into a common pathway leading to neurodegeneration. R-APO, previously shown by us to protect against MPTP neurotoxicity, prevented the over expression of several genes known to participate in cell death. cDNA microarrays will provide new prospects to study and identify various mechanism of neurodegeneration and neuroprotection not feasible with conventional biochemical procedures, as well as new prospects to develop effective neuroprotective drugs. PMID- 11205136 TI - Common properties for propargylamines of enhancing superoxide dismutase and catalase activities in the dopaminergic system in the rat: implications for the life prolonging effect of (-)deprenyl. AB - (-)Deprenyl has been reported to prolong the life span of different animal species. Further, the drug effectively increases antioxidant enzyme activities such as superoxide dismutase (SOD) and catalase (CAT) in brain dopaminergic regions. We have found that the effect of the drug on antioxidant enzyme activities is highly dose dependent, increasing with an increasing dose, however, a higher dose becomes less effective and an excessive dose becomes adversely effective. Most importantly, an optimal dose for the effect varies widely depending on animal species, strain, sex, age and duration of the treatment, which may at least partly explain discrepancies reported among different studies in the past. From the parallelism of the dose-effect relationship of the drug between life span extension and increasing endogenous antioxidant enzyme activity, we have suggested that the above two effects of (-)deprenyl may be causally related. This review summarizes our past series of studies and also reports our very recent observation that other propargylamines such as rasagiline and (R)-N-(2-heptyl)-N-methylpropagylamine (R-2HMP) also share the property of enhancing antioxidant enzyme activities. Further, our most recent study has found that these propargylamines increase antioxidant enzyme activities not only in brain dopaminergic regions but in extra-brain dopaminergic tissues such as the heart and kidneys. These observations are discussed in relation to the life prolonging effect of (-)deprenyl reported in the past. PMID- 11205137 TI - TV3326, a novel neuroprotective drug with cholinesterase and monoamine oxidase inhibitory activities for the treatment of Alzheimer's disease. AB - TV3326, [(N-propargyl-(3R) aminoindan-5-yl)-ethyl methyl carbamate] is a novel aminoindan derivative of the selective irreversible monoamine oxidase (MAO)-B inhibitor, rasagiline (N-propargyl-(1R)-aminoindan), possessing both cholinesterase (ChE) and MAO-inhibitory activity. In doses of 35-100 micromoles/kg administered orally to rats, it inhibits ChE by 25-40% and antagonises scopolamine-induced impairments in spatial memory. After daily administration of 75 micromoles/kg for 2 weeks, TV3326 does not show any motor stimulant effects but significantly reduces immobility in the forced swim test, an action consistent with that of known antidepressants. This could result from more than 70% inhibition of both MAO-A and B in the brain that occurs under these conditions, since it is not shared by the S-isomer, TV3279, which does not block MAO. TV3326 also shows selectivity for brain MAO, even after 2 months of daily administration, with little or no effect on the enzyme in the intestinal tract and liver. This reduces the likelihood of it producing the "cheese effect" if administered with tyramine-containing foods or beverages. TV3326 and TV3279 protect against ischemia-induced cytotoxicity in PC12 cells and reduce the oedema, deficits in motor function and memory after closed head injury in mice. These neuroprotective effects do not result from MAO inhibition. The pharmacological actions of TV3326 could be of clinical importance for the treatment of AD, and the drug is currently in development for this purpose. PMID- 11205138 TI - Neurotoxins induce apoptosis in dopamine neurons: protection by N-propargylamine 1(R)- and (S)-aminoindan, rasagiline and TV1022. AB - In Parkinson's disease, apoptosis was proposed to cause cell death in nigral dopamine neurons. An endogenous dopaminergic neurotoxin, N-methyl(R)salsolinol, stereo-selectively induced apoptosis in human neuroblastoma SH-SY5Y cells. In this paper the intracellular mechanism of apoptosis was studied using N methyl(R)salsolinol, 6-hydroxydopamine and peroxynitrite as inducers of apoptosis. Apoptotic cascade was initiated by opening of mitochondrial permeability transition pore, as shown by collapse of mitochondrial membrane potential, deltapsim. Apoptosis was executed by caspase 3 activation, followed by DNA fragmentation, which was antagonized by overexpressed Bcl-2. Propargylamines were found to protect the cells from apoptosis, and rasagiline, a selective irreversible inhibitor of type B monoamine oxidase was the most potent to prevent the cell death. Rasagiline preserved deltapsim, which was proved also in isolated mitochondria, and rasagiline completely suppressed the activation of caspases and DNA fragmentation. These results suggest that mitochondria regulate apoptotic process, which may be a target of neuroprotection by rasagiline. PMID- 11205139 TI - Homocysteine and alcoholism. AB - Chronic alcohol consumption can induce alterations in the function and morphology of most if not all brain systems and structures. However, the exact mechanism of brain damage in alcoholics remains unknown. Partial recovery of brain function with abstinence suggests that a proportion of the deficits must be functional in origin (i.e. plastic changes of nerve cells) while neuronal loss from selected brain regions indicates permanent and irreversible damage. There is growing evidence that chronic alcoholism is associated with a derangement in the sulfur amino acid metabolism. Recently, it has been shown that excitatory amino acid (EAA) neurotransmitters and homocysteine levels are elevated in patients who underwent withdrawal from alcohol. Furthermore, it has been found that homocysteine induces neuronal cell damage by stimulating NMDA receptors as well as by producing free radicals. Homocysteine neurotoxicity via overstimulation of N-methyl-D-aspartate receptors may contribute to the pathogenesis of both brain shrinkage and withdrawal seizures linked to alcoholism. PMID- 11205140 TI - Neurorescuing effects of the GAPDH ligand CGP 3466B. AB - (-)-Deprenyl, used for the treatment of Parkinson's disease, was reported to possess neurorescuing/antiapoptotic effects independent of its MAO-B inhibiting properties. It is metabolized to (-)-desmethyldeprenyl, which seems to be the active principle, and further to (-)-amphetamine and (-)-methamphetamine, which antagonize its rescuing effects. These complications may explain the limited neurorescuing potential of (-)-deprenyl observed clinically. CGP 3466 (dibenzo[b,f]oxepin-10-ylmethyl-methyl-prop-2-ynyl-amine), structurally related to (-)-deprenyl, exhibits virtually no MAO-B nor MAO-A inhibiting properties and is not metabolized to amphetamines. It was shown to bind to glyceraldehyde-3 phosphate dehydrogenase, a glycolytic enzyme with multiple other functions including an involvement in apoptosis, and shows neurorescuing properties qualitatively similar to, but about 100-fold more potent than those of (-) deprenyl in several in vitro and in vivo paradigms. In concentrations ranging from 10(-13)-10(-5) M, it rescues partially differentiated PC12 cells from apoptosis induced by trophic withdrawal, cerebellar granule cells from apoptosis induced by cytosine arabinoside, rat embryonic mesencephalic dopaminergic cells from death caused by MPP+, and PAJU human neuroblastoma cells from death caused by rotenone. However, it did not affect apoptosis elicited by a variety of agents in rapidly proliferating cells from thymus or skin or in liver or kidney cells. In vivo, it rescued facial motor neuron cell bodies in rat pups after axotomy, rat hippocampal CA1 neurons after transient ischemia/hypoxia, and mouse nigral dopaminergic cell bodies from death induced by MPTP, in doses ranging between 0.0003 and 0.1 mg/kg p.o. or s.c., depending on the model. It also partially prevented the loss of tyrosine hydroxylase immunoreactivity in the substantia nigra of 6-OHDA-lesioned rats and improved motor function in these animals. Moreover, it prolonged the life-span of progressive motor neuronopathy (pmn) mice (a model for ALS), preserved their body weight and improved their motor performance. This was accompanied by a decreased loss of motor neurons and motor neuron fibers, and protection of mitochondria. The active concentration- or dose ranges in the different in vitro and in vivo paradigms were remarkably similar. In several paradigms, bell-shaped dose-response curves were observed, the rescuing effect being lost above about 1 mg/kg, a fact that must be considered in clinical investigations. PMID- 11205141 TI - The enigma of cell death in neurodegenerative disorders. AB - Progressive cell loss in specific neuronal populations is the pathological hallmark of neurodegenerative diseases, but its mechanisms remain unresolved. Apoptotic cell death has been implicated as a major mechanism in Alzheimer disease (AD), Parkinson disease (PD) and other neurodegenerative disorders. However, DNA fragmentation in human brain as a sign of neuronal cell injury is too frequent to account for the continuous loss in these slowly progressive diseases. In a series of autopsy confirmed cases of AD, PD, related disorders, and age-matched controls, DNA fragmentation using the TUNEL method, an array of apoptosis-related proteins (ARP), proto-oncogenes, and activated caspase-3, the key enzyme of late-stage apoptosis, were examined. In AD, a considerable number of hippocampal neurons and glial cells showed DNA fragmentation with a 3- to 6 fold increase related to neurofibrillary tangles and amyloid deposits, but only 1 in 2.600 to 5.600 neurons displayed apoptotic morphology and cytoplasmic immunoreactivity for activated caspase-3, whereas no neurons were labeled in age matched controls. caspase-3 immunoreactivity was seen in granules of cells with granulovacuolar degeneration, in around 25% co-localized with early cytoplasmic deposition of tau-protein. In progressive supranuclear palsy, only single neurons and several oligodendrocytes in brainstem, some with tau-deposits, were TUNEL positive and expressed both ARPs and activated caspase-3. In PD, dementia with Lewy bodies, multisystem atrophy (MSA), and corticobasal degeneration, TUNEL positivity and expression of ARPs or activated caspase-3 were only seen in microglia and oligodendrocytes with cytoplasmic inclusions, but not in neurons. These data provide evidence for extremely rare apoptotic neuronal death in AD and PSP compatible with the progression of neuronal degeneration in these chronic diseases. Apoptosis mainly involves reactive microglia and oligodendroglia, the latter often involved by deposits of insoluble fibrillary proteins, while alternative mechanisms of neuronal death may occur. Susceptible cell populations in a proapoptotic environment show increased vulnerability towards metabolic or other noxious factors, with autophagy as a possible protective mechanism in early stages of programmed cell death. The intracellular cascade leading to cell death still awaits elucidation. PMID- 11205142 TI - The neuroprotective effects of CGP 3466B in the best in vivo model of Parkinson's disease, the bilaterally MPTP-treated rhesus monkey. AB - The propargylamine CGP 3466B prevents dopamine cell death both in vitro and in rodent models of Parkinson's disease. The present study investigates the efficacy of this compound to prevent the behavioral consequences of dopaminergic cell death in the best animal model of Parkinson's disease, the bilaterally MPTP treated monkey. Rhesus monkeys were bilaterally treated with MPTP, using a two step procedure: 2.50 mg MPTP was infused into the left carotid artery followed by a second bolus of 1.25 mg into the right carotid artery, 8 weeks later. Subcutaneous injection of either 0.014 mg/kg CGP 3466B (n = 4) or its solvent (distilled water; n = 4), twice daily for fourteen days, started two hours after the second MPTP infusion. A Parkinson rating scale was assessed for the evaluation of the effects. After the first MPTP treatment, the monkeys developed mild to moderate parkinsonian symptoms. The second MPTP treatment strongly increased the severity of Parkinson scores in all control monkeys, as assessed on day 3, 7, 14, 21, 28 and 35 after the second MPTP treatment. In contrast, CGP 3466B nearly completely prevented the increase of parkinsonian symptoms after the second MPTP treatment. The therapeutic effects of CGP 3466B were still present after a washout period of 3 weeks, implying that the effects were not symptomatic. These data are the first to show that the systemic administration of CGP 3466B is able to prevent the development of MPTP-induced motor symptoms in primates. This compound may have great value for inhibiting the progression of the neurodegenerative process in patients with Parkinson's disease. PMID- 11205143 TI - Neurotrophic effects of central nicotinic receptor activation. AB - A growing number of data have shown that compounds interacting with neuronal nicotinic acetylcholine receptors (nAChRs) have, both in vivo and in vitro, the potential to be neuroprotective and that treatment with nAChR agonists elicit long-lasting improvement of cognitive performance in a variety of behavioural tests in rats, monkeys and humans. Epidemiological and clinical studies suggested also a potential neuroprotective/trophic role of (-)-nicotine in neurodegenerative disease, such as Alzheimer's disease and Parkinson's disease. This neuroprotective/trophic role of nAChR activation has been mainly mediated by alpha7 and alpha4beta2 nAChR subtypes, as evidenced using selective nAChR antagonists, and by potent nAChR agonists recently found displaying efficacy and/or larger selective affinities than (-)-nicotine for neuronal nAChR subtypes. A neurotrophic factor gene regulation by nAChR signalling has been taken into consideration as a possible mechanism involved in neuroprotective/trophic effects of nAChR activation and has given evidence that the fibroblast growth factor (FGF 2) gene is a target for nAChR signalling. These findings suggested that FGF-2 could be involved, in view of its neurotrophic functions, in nAChR mechanisms mediating neuronal survival, trophism and plasticity. PMID- 11205144 TI - Regulation of neuronal cell death and differentiation by NGF and IAP family members. AB - Nerve growth factor (NGF) and other neurotrophins were identified because of their trophic role for distinct populations of neurons in the peripheral nervous system. We know that neuronal cell death is regulated by a genetically encoded programme, called apoptosis, that is conserved from worms to humans. Dysregulation of this programme is thought to contribute to neurodegenerative diseases which are characterized by the loss of neurons. This article will review recent findings about the motoneuron disease spinal muscular atrophy (SMA). Two closely linked candidate genes for SMA, the SMN (survival motor neuron) gene and the NAIP (neuronal apoptosis inhibitory protein) gene have been reported. The SMN protein forms a complex with several other proteins and this complex containing SMN plays a critical role in the assembly of spliceosomes and in pre-mRNA splicing. NAIP, c-IAP1 (inhibitor of apoptosis-1), c-IAP2, X-IAP and survivin comprise the mammalian inhibitor of apoptosis family. Its members can protect mammalian cells from apoptosis induced by a variety of stimuli. Some of the IAP molecules have been shown to interact both with cell signalling molecules and with specific caspases but details concerning their cellular role are only incompletely characterized. PMID- 11205145 TI - Insulin-like growth factor-1 (IGF-1): a neuroprotective trophic factor acting via the Akt kinase pathway. AB - Insulin-like growth factor-I (IGF-I) is a pleiotropic polypeptide with a wide range of actions in both central and peripheral nervous sytems. Over the past few years, we studied the trophic as well as neuromodulatory roles of IGF-I in the brain. Accumulated evidence indicates that IGF-I, apart from regulating growth and development, protects neurons against cell death induced by amyloidogenic derivatives, glucose or serum deprivation via the activation of intracellular pathways implicating phosphatidylinositide 3/Akt kinase, winged-helix family of transcription factor FKHRL1 phosphorylation or production of free radicals. The effects of IGF-I on neuroprotection, glucose metabolism and activity-dependent plasticity suggest the potential usefulness of this growth factor or related mimetics in the treatment of Alzheimer's disease and other neurodegenerative disorders. PMID- 11205146 TI - GDF-15/MIC-1 a novel member of the TGF-beta superfamily. AB - We have cloned, expressed, and raised antibodies against a novel member of the TGF-beta superfamily, growth/differentiation factor-15 (GDF-15). The predicted protein is identical to macrophage inhibitory cytokine-1 (MIC-1), which was discovered simultaneously. GDF-15 is a more distant member of the TGF-beta superfamily and does not belong to one of the known TGF-beta subfamilies. In the CNS, GDF-15/MIC-1 mRNA is abundantly expressed by the choroid plexus. In addition we have preliminary evidence that GDF-15/MIC-1 is a potent trophic factor for selected classes of neurons in vitro and in vivo. Thus, GDF-15 is a novel neurotrophic factor with prospects for the treatment of disorders of the CNS. PMID- 11205148 TI - Psychiatric complications in Parkinson's disease. AB - Parkinson's disease (PD) is caused by an abnormal degeneration of the dopamine (DA) producing cells in the substantia nigra (SN) and ventral tegmentum area (VTA) in combination with a varying decay of the noradrenergic (locus coeruleus), cholinergic forebrain (nucleus basalis of Meynert) and serotoninergic (dorsal raphe nuclei) systems, leading to a multitude of motor and non-motor behavioral disturbances, known as parkinsonism. Normally, main dopamine depletion is restricted to the SN region with manifest (non)motor behavioral abnormalities caused by the inability to spontaneously switch between intern-cued cortical behavioral programmes. Clinical symptoms comprise motoric abnormalities, though subtle cognitive disturbances as well as psychological dysfunction with loss of mental flexibility and reactive depressive symptoms might be seen. These symptoms might be compensated in part by externally-cued behavior. PMID- 11205147 TI - Changes in cytokines and neurotrophins in Parkinson's disease. AB - Degeneration of the dopamine (DA) neurons of the substantia nigra pars compacta and the resulting loss of nerve terminals accompanied by DA deficiency in the striatum are responsible for most of the movement disturbances called parkinsonism, observed in Parkinson's disease (PD). One hypothesis of the cause of degeneration of the nigrostriatal DA neurons is that PD is caused by programmed cell death (apoptosis) due to increased levels of cytokines and/or decreased ones of neurotrophins. We and other workers found markedly increased levels of cytokines, such as tumor necrosis factor (TNF)-alpha, interleukin (IL) 1beta, IL-2, IL-4, IL-6, transforming growth factor (TFG)-alpha, TGF-beta1, and TGF-beta2, and decreased ones of neurotrophins, such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), in the nigrostriatal DA regions and ventricular and lumbar cerebrospinal fluid of PD patients. Furthermore, the levels of TNF-alpha receptor R1 (TNF-R1, p55), bcl-2, soluble Fas (sFas), and the activities of caspase-1 and caspase-3 were also elevated in the nigrostriatal DA regions in PD. In experimental animal models of PD, IL-1beta level was increased and NGF one decreased in the striatum of 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian mice, and TNF-alpha level was increased in the substantia nigra and striatum of the 6-hydroxydopamine (6OHDA)-injected side of hemiparkinsonian rats. L-DOPA alone or together with 6OHDA does not increase the level of TNF-alpha in the brain in vivo. Increased levels of proinflammatory cytokines, cytokine receptors and caspase activities, and reduced levels of neurotrophins in the nigrostriatal region in PD patients, and in MPTP- and 6OHDA-produced parkinsonian animals suggest increased immune reactivity and programmed cell death (apoptosis) of neuronal and/or glial cells. These data indicate the presence of such proapoptotic environment in the substantia nigra in PD that may induce increased vulnerability of neuronal or glial cells towards a variety of neurotoxic factors. The probable causative linkage among the increased levels of proinflammatory cytokines and the decreased levels of neurotrophins, candidate parkinsonism-producing neurotoxins such as isoquinoline neurotoxins (Review; Nagatsu, 1997), and the genetic susceptibility to toxic factors, remains for further investigation in the molecular mechanism of PD. The increased cytokine levels, decreased neurotrophin ones, and the possible immune response in the nigrostriatal region in PD indicate new neuroprotective therapy including nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, immunosuppressive or immunophilin-binding drugs such as FK-506, and drugs increasing neurotrophins. PMID- 11205149 TI - Dementia with Lewy bodies: prevalence, clinical spectrum and natural history. AB - The article summarises history, terminology, the clinical and neuropathological diagnostic criteria, neurochemical and genetic findings, sensitivity and specificity of the clinical diagnostic criteria, prevalence, demographical data and nosology, differential diagnosis, and therapy of dementia with Lewy bodies (DLB). DLB shares clinical symptoms of Parkinson's disease and dementia of the Alzheimer-type (DAT). However, DLB is also different to PD and DAT (less tremor and asymmetry of the motor symptoms, more falls, and less favourable response to L-Dopa than PD; in contrast to DAT marked cognitive fluctuations and phases of reduced alertness, hallucinations and delirium). There are genetic similarities to DAT and PD in terms of common genetic risk factors. A genetic cause of the disease has so far not been detected. Whether or not DLB is a disease entity or an association of diseases (Lewy body disease and DAT) has so far not been elucidated. Clinical distinction from DAT and PD has clinical importance because of different therapeutic and prognostic implications. Studies are needed to standardize the treatment of motor, cognitive, psychiatric and vegetative symptoms. PMID- 11205150 TI - Neuronal degeneration and reorganization: a mutual principle in pathological and in healthy interactions of limbic and prefrontal circuits. AB - Based on developmental principles and insights from animal research about neuroplasticity in cell assemblies, this article is to propose a view of plasticity that promotes a link between hippocampal and prefrontal structure and function. Both the mitotic activity (counting of BrdU-labeled cells) in hippocampal dentatus and the maturation of dopamine fibres (quantitative immunochemistry of mesoprefrontal projection) in the prefrontal cortex proved to be a measurable combination for investigating the complex chain of events that relate activity dependent neuroplasticity to normal as well as to pathological maturational processes. With our animal model we demonstrate that both rearing conditions and neuroactive substances can effectively interfere with developmental plasticity and induce a malfunctional adaptation of prefrontal structures and neurotransmitter systems (dopamine, GABA). In the hippocampal dentatus, where ontogenetic plasticity proved to be preserved by continued neuro- and synaptogenesis, serious damage can be internalized without simultaneous disruption of neural dynamics offering an approach to reverse dysfunctional reorganization in the prefrontal cortex. PMID- 11205151 TI - Depression in alpha-synucleinopathies: prevalence, pathophysiology and treatment. AB - Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA) are increasingly recognized as alpha-synucleinopathies, i.e. neurodegenerative disorders that share a common subcellular pathology characterized by alpha-synuclein abnormal aggregation. In the present review we focus on depression in alpha-synucleinopathies, discussing epidemiological, pathophysiological and treatment aspects of this frequently disabling clinical feature which may occur in PD, DLB and MSA alike. PMID- 11205152 TI - The serotonin transporter in Alzheimer's and Parkinson's disease. AB - The etiology of late-onset Alzheimer's disease (AD) and idiopathic Parkinson's disease (PD) is not known. In both disorders there is an extensive degeneration of serotonergic neurons, with corresponding losses of the serotonin (5HT) transporter (5HTT), which is responsible for the reuptake of 5HT from the synaptic cleft. An increasing body of evidence indicates that allelic variation of the 5HTT gene promoter (5HTT gene-linked polymorphic region, 5HTTLPR) determines high or low 5HT uptake in normal human brain. Association studies show that the low-activity allele of the 5HTTLPR is a risk factor for late-onset AD. In PD, the 5HTTLPR influences the risk of developing depression, a common symptom in PD patients. A compromised serotonergic system thus plays an important role in the pathophysiology of both AD and PD. PMID- 11205153 TI - Immunopathogenic and clinical relevance of antibodies against myelin oligodendrocyte glycoprotein (MOG) in Multiple Sclerosis. AB - Recent neuropathological findings identified four distinct immunopathogenic pathways of demyelination and tissue destruction in the most common inflammatory demyelinating central nervous system disorder, Multiple Sclerosis. One of this neuropathological subtypes is characterised by features of antibody-mediated demyelination. A role of anti-myelin antibodies in the disease evolution of multiple sclerosis has been suggested already for a long time, however, their pathogenetic and clinical relevance is not understood yet. This present article will discuss recently published and some preliminary data on the immunopathogenic role of antibodies against myelin oligodendrocyte glycoprotein (MOG) and other myelin/nonmyelin targets in multiple sclerosis, as well as possible clinical implications for prognosis and therapy in the future. PMID- 11205154 TI - Lessons from studies of antigen-specific T cell responses in Multiple Sclerosis. AB - Multiple Sclerosis (MS) is considered a T cell-mediated autoimmune disease of central nervous system myelin. Based on elegant experiments in an animal model of MS, experimental allergic encephalomyelitis (EAE), a number of myelin proteins and peptides derived from these can induce inflammatory demyelinating lesions. Recent studies with transgenic mice expressing human HLA-DR molecules and a myelin basic protein (MBP)-specific T cell receptor as well as data from a phase II clinical trial with an altered peptide ligand based on MBP peptide (83-99) provide convincing evidence that the pathogenetic concepts which largely stem from the above EAE studies are valid in MS, too. PMID- 11205155 TI - Impaired iron homeostasis in Parkinson's disease. AB - Despite physiological systems designed to achieve iron homeostasis, increased concentrations of brain iron have been demonstrated in a range of neurodegenerative diseases. These including the parkinsonian syndromes, the trinucleotide repeat disorders and the dementia syndromes. The increased brain iron is confined to those brain regions most affected by the degeneration characteristic of the particular disorder and is suggested to stimulate cell damage via oxidative mechanisms. Changes in central iron homeostasis have been most closely investigated in PD, as this disorder is well characterised both clinically and pathologically. PD is associated with a significant increase in iron in the degenerating substantia nigra (SN) and is measureable in living PD patients and in post-mortem brain. This increase, however, occurs only in the advanced stages of the disease, suggesting that this phenonoma may be a secondary, rather than a primary initiating event, a hypothesis also supported by evidence from animal experiments. The source of the increased iron is unknown but a variety of changes in iron homeostasis have been identified in PD, both in the brain and in the periphery. The possibility that an increased amount of iron may be transported into the SN is supported by data demonstrating that one form of the iron-binding glycoprotein transferrin family, lactotransferrin, is increased in surviving neurons in the SN in the PD brain and that this change is associated with increased numbers of lactotransferrin receptors on neurons and microvessels in the parkinsonian SN. These changes could represent one mechanism by which iron might concentrate within the PD SN. Alternatively, the measured increased in iron might result from a redistribution of ferritin iron stores. Ferritin is located in glial cells while the degenerating neurons do not stain positive for ferritin. As free radicals are highly reactive, it is unlikely that glial-derived free radicals diffuse across the intracellular space in sufficent quantities to damage neuronal constituents. If intracellular iron release contributes to neuronal damage it seems more probable that an intraneuronal iron source is responsible for oxidant-mediated damage. Such a iron source is neuromelanin (NM), a dark coloured pigment found in the dopaminergic neurons of the human SN. In the normal brain, NM has the ability to bind a variety of metals, including iron, and increased NM-bound iron is reported in the parkinsonian SN. The consequences of these phenomena for the cell have not yet been clarified. In the absence of significant quantities of iron NM can act as an antioxidant, in that it can interact with and inactivate free radicals. On the other hand, in the presence of iron NM appears to act as a proxidant, increasing the rate of free radical production and thus the oxidative load within the vulnerable neurons. Given that increased iron is only apparent in the advanced stages of the disease it is unlikely that NM is of importance for the primary aetiology of PD. A localised increase in tissue iron and its interaction with NM may be, however, important as a secondary mechanism by increasing the oxidative load on the cell, thereby driving neurodegeneration. PMID- 11205156 TI - Glutamate excitotoxicity--a mechanism for axonal damage and oligodendrocyte death in Multiple Sclerosis? AB - Glutamate excitotoxicity mediated by the AMPA/kainate-type of glutamate receptors is known not only to damage neurons but also the myelin-producing cell of the central nervous system (CNS), the oligodendrocyte. In Multiple Sclerosis (MS), myelin, oligodendrocytes and axons are lost or damaged as a result of an inflammatory attack on the CNS. Activated immune cells produce glutamate in large quantities by deamidating glutamine via glutaminase. Thus, we hypothesized that during inflammation in MS, glutamate excitotoxicity may contribute to the lesion. This was addressed by treating mice sensitized to develop acute experimental autoimmune encephalomyelitis (EAE) with an AMPA/kainate antagonist, NBQX. Treatment resulted in substantial amelioration of disease, increased oligodendrocyte survival and reduced axonal damage, as indicated by the levels of dephosphorylated neurofilament-H. Despite the clinical differences, NBQX treatment had no effect on lesion size and did not reduce the degree of CNS inflammation. In addition, NBQX did not alter the proliferative activity of antigen-primed T cells in vitro, further indicating a lack of effect at the level of the immune system. In separate studies, infiltrating immune cells present in perivascular cuffs, commonly the site of entry for invading immune cells, were found to express glutaminase in abundance, supporting the production of glutamate in inflammatory lesions. Thus, glutamate excitotoxicity appears to be an important mechanism in autoimmune demyelination and its prevention with AMPA/kainate antagonists may prove to be an effective therapy for MS. PMID- 11205157 TI - Evidence for enhanced neuro-inflammatory processes in neurodegenerative diseases and the action of nitrones as potential therapeutics. AB - A brief review is presented on observations leading to the current notions regarding neuro-inflammatory processes. The greatest focus is on Alzheimer's disease (AD) since this is where the most convincing data has been obtained. A brief summary of observations on the neuroprotective action of alpha-phenyl-tert butyl-nitrone (PBN) as well as results of research designed to understand its mechanism of action is presented. We hypothesize that the mechanism of action of PBN involves inhibition of signal transduction processes, which are involved in the upregulation of genes mediated by pro-inflammatory cytokines and H2O2 that cause formation of toxic gene products. Results from recent experiments on Kainic acid (KA) mediated brain damage are provided to suggest the validity of the in vivo action of PBN to inhibit neuro-inflammatory processes. The accumulating scientific facts are helping to provide concepts that may become the basis for novel therapeutic approaches to the treatment of several neurodegenerative diseases. PMID- 11205158 TI - The molecular mechanism of dopamine-induced apoptosis: identification and characterization of genes that mediate dopamine toxicity. AB - Parkinson's disease (PD) is a progressive neurological disorder caused by rather selective degeneration of the dopaminergic (DA) neurons in the substantia nigra. Though subject to intensive research, the etiology of this nigral neuronal loss is still enigmatic and treatment is basically symptomatic. The current major hypothesis suggests that nigral neuronal death in PD is due to excessive oxidative stress generated by auto- and enzymatic oxidation of the endogenous neurotransmitter dopamine (DA), the formation of neuromelanin and presence of high concentrations of iron. We have found that DA toxicity is mediated through its oxidative metabolites. Whereas thiol-containing antioxidants provided marked protection against DA toxicity, ascorbic acid accelerated DA-induced death. Using the differential display approach, we sought to isolate and characterize genes whose expression is altered in response to DA toxicity. We found an upregulation of the collapsin response mediator protein (CRM) and TCP-1delta in sympathetic neurons, which undergo dopamine-induced apoptosis. The isolation of these genes led us to examine the expression and activity of CRM and TCP-1delta related genes. Indeed, we found a significant induction of mRNAs of the secreted collapsin-1 and the mitochondrial stress protein HSP60. Antibodies directed against collapsin-1 provided marked and prolonged protection of several neuronal cell types from dopamine-induced apoptosis. In a parallel study, using antisense technology, we found that inhibition of TCP-1delta expression significantly reduced DA-induced neuronal death. These findings suggest a functional role for collapsin-1 and TCP-1delta as positive mediators of DA-induced neuronal apoptosis. PMID- 11205159 TI - Glyceraldehyde-3-phosphate dehydrogenase in neurodegeneration and apoptosis signaling. AB - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a well-studied glycolytic enzyme that plays a key role in energy metabolism. GAPDH catalyzes the conversion of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate in the glycolytic pathway. As part of the conversion, GAPDH converts NAD+ to the high-energy electron carrier NADH. GAPDH has been referred to as a "housekeeping" protein and based on the view that GAPDH gene expression remains constant under changing cellular conditions, the levels of GAPDH mRNA have frequently been used to normalize northern blots. In recent years, that view has changed since GAPDH is now known to contribute to a number of diverse cellular functions unrelated to glycolysis. Normative functions of GAPDH now include nuclear RNA export, DNA replication, DNA repair, exocytotic membrane fusion, cytoskeletal organization and phosphotransferase activity. Pathologically, GAPDH has been implicated in apoptosis, neurodegenerative disease, prostate cancer and viral pathogenesis (see Sirover (1999) for a recent review of GAPDH functions). Most recently, it has been shown that GAPDH is a target for deprenyl related compounds (Carlile et al., 2000; Kragten et al., 1998) and may contribute to the neuroprotection offered by those compounds. PMID- 11205160 TI - Feline panleukopenia virus revisited: molecular characteristics and pathological lesions associated with three recent isolates. AB - The low incidence of clinical signs or pathological lesions compatible with feline panleukopenia in cats has created the perception among practitioners that the disease has disappeared since the emergence of canine parvovirus type 2 in the late 1970s. Three parvoviruses that were recently isolated from a domestic cat and 2 cheetahs in cell culture or detected by means of the polymerase chain reaction were shown to be typical feline parvoviruses. Phylogenetic comparison with other FPV isolates did not reveal a particular African cluster. PMID- 11205161 TI - A study to evaluate the field efficacy of ivermectin, fenbendazole and pyrantel pamoate, with preliminary observations on the efficacy of doramectin, as anthelmintics in horses. AB - The efficacy of ivermectin, fenbendazole, pyrantel pamoate and doramectin was evaluated under field conditions at 2 sites in the Free State Province of South Africa. The study involved 25 horses at each site, divided into 5 groups of equal size. Ivermectin, fenbendazole and pyrantel pamoate were administered orally at doses of 0.2, 10 and 19 mg/kg respectively. Doramectin was administered by intramuscular injection at a dose of 0.2 mg/kg. Treatment efficacy was based on the mean faecal egg count reduction 14 days post treatment. At site A a faecal egg count reduction of 100% was found after treatment with ivermectin, fenbendazole and doramectin. A 96.1% reduction was found after treatment with pyrantel pamoate. At site B ivermectin and doramectin produced a 100% reduction in faecal egg counts, fenbendazole produced an 80.8% reduction and pyrantel pamoate a 94.1% reduction. Doramectin produced a 100% reduction in faecal egg counts at both sites, despite not being registered for use in horses. In addition, the results indicated reduced efficacy of fenbendazole at site B, which suggested benzimidazole resistance. Larval cultures showed that cyathostomes accounted for between 86 and 96% of pre-treatment parasite burdens at both sites. Other helminths identified in the faecal samples were Strongylus spp. and Trichostrongylus axei. PMID- 11205162 TI - A preliminary evaluation of a sheep blowfly trap in the Western Cape. AB - An insecticide-free sheep blowfly trapping system, utilising a synthetic lure, was evaluated at 4 localities in the Western Cape. Control sites, where no suppression was practised, were identified for each locality. The blowfly population was monitored for 48 hours monthly at each of the localities. Five to 7 suppression traps at the respective localities were identified for this purpose. Three to 10 traps were set monthly for monitoring in the control areas. Trapping resulted in the suppression (P < 0.01) of the Lucilia population at Caledon, where a large area of approximately 50 km2 was trapped. The suppression area of all the localities was < or =850 ha. At Elsenburg, blowfly numbers were low. There was a strong suggestion of a general reduction in the Lucilia numbers at this locality. Trapping failed to reduce Lucilia numbers at Tygerhoek and Langgewens. Lack of control over the influx of Lucilia from adjacent sheep producing areas probably contributed to this result. The observed response at Elsenburg was probably due to its situation in a predominantly wine-growing area. Most of the blowflies recovered from the control traps during the month with the highest yield at the respective localities belonged to the genus Lucilia. The results obtained at Caledon and published reports suggest that large-scale trapping of Lucilia spp. may play a role in an integrated pest management system for blowflies. PMID- 11205163 TI - Clinical, cardiopulmonary and haemocytological effects of xylazine in goats after acute exposure to different environmental temperature and humidity conditions. AB - This study was carried out to assess the influence of xylazine administration on clinical, cardiopulmonary and haemocytological variables after acute exposure to different environmental conditions. Xylazine hydrochloride was administered intravenously at 0.1 mg/kg body mass to 6 clinically healthy, castrated male goats. All animals were exposed for 60 min to 3 sets of climatic conditions: 14 degrees C, 33% relative humidity; 24 degrees C, 55% RH, and 34 degrees C, 65% RH. The variables that were measured for a period of 60 min after xylazine administration were sedation, analgesia, salivation, urination, ventilation rate, heart-rate, mean arterial blood pressure, oesophageal temperature, haematocrit, mean corpuscular volume and mean corpuscular haemoglobin concentration. Xylazine induced sedation, analgesia, salivation and urination independently of the 3 environmental conditions. Environment had no influence on the onset, duration and recovery from sedation. In the 14 degrees C environment, xylazine resulted in a significant decrease in ventilation and heart-rate from baseline values. Significant changes in mean arterial blood pressure, haemoglobin concentration, mean corpuscular volume, haematocrit and red cell count were observed in the 3 environments. Total plasma protein was significantly altered at 24 degrees C and 34 degrees C. Acute exposure of goats to different environmental conditions had no significant influence on the clinical, cardiopulmonary and haemocytological variables. Physiological changes induced by xylazine were therefore independent of the environment. PMID- 11205164 TI - Characteristics and performance of village animal health workers and veterinary assistants in northern Malawi. AB - Fourty-two village animal health workers called keymen (KM) and 84 veterinary assistants (VA) involved in a Basic Animal Health Service (BAHS) Programme in northern Malawi were interviewed during 1998. The general characteristics and perceptions of both groups were analysed using uni- and multivariate techniques. Detailed sales and treatment patterns of six KM and 12 VA were evaluated for the period September 1996 to August 1997. Results indicated an overall job satisfaction for 82% of KM and 83 % of VA. Estimated weekly involvement in livestock service delivery, particularly of KM, was 3.7 days on average. Total annual drug sales of KM and VA between 1996 and 1997 on average were equivalent to US$ 124 and US$ 218 respectively. Most livestock remedies were issued for treatment of calves, followed by adult cattle, chickens and small ruminants. The changes suggested by VA and KM in order to improve field performance focused on regular refresher training by the BAHS programme. PMID- 11205165 TI - Routine veterinary anaesthetic management practices in South Africa. AB - A survey of the routine anaesthetic management of dogs and cats during sterilisation by veterinarians in South Africa was conducted. This report describes the premedication, induction and maintenance agents most commonly used in dogs and cats. Information about monitoring of patients during the procedure and who is responsible for induction of anaesthesia and monitoring was obtained. Questionnaires were analysed with regard to demographic data, practice size, continuing education, the number of surgical procedures and sterilisations performed per week and an estimate of yearly mortality. Acetylpromazine is the most commonly used premedication in dogs and xylazine in cats. Thiopentone in dogs and alphaxalone/alphadolone in cats were the induction agents most commonly used. Alphaxalone/alphadolone in cats and halothane in dogs are the most commonly used maintenance agents. Records of anaesthesia are poorly kept and monitoring of patients is poorly performed. Respiratory rate is the parameter most commonly monitored (90.7%), and in most cases is the sole parameter. On average 10.34 +/- 8.25 cats were operated per week, of which 5.45 +/- 5.60 were sterilised; 17.79 +/- 11.61 dogs were operated per week, of which 8.65 +/- 7.10 were sterilised. In total, 190 patients died under anaesthesia, a mortality rate of 1:1,243. Just over 50% of practitioners had attended continuing education courses during their careers. PMID- 11205166 TI - The spread of weeds into sensitive areas by seeds in horse faeces. AB - The possible spread by horse faeces of plants that may become weeds in sensitive areas was investigated. It was found that the period 24-48 hours after ingestion of seeds included in rations was the retention time for seeds passing through the digestive system of the horse. The ability of seeds to germinate was not influenced by exposure to digestive fluids or sea-water. A feeding regime of compound feeds is suggested. PMID- 11205167 TI - Ectoparasites of dogs belonging to people in resource-poor communities in North West Province, South Africa. AB - A total of 344 dogs belonging to people in resource-poor communities in North West Province, South Africa, was examined for ectoparasites, and all visible arthropods were collected from the left side of each dog. By doubling these numbers it was estimated that the dogs harboured 14,724 ixodid ticks, belonging to 6 species, 1,028 fleas, belonging to 2 species, and 26 lice. Haemaphysalis leachi accounted for 420 and Rhipicephalus sanguineus for 14,226 of the ticks. Pure infestations of H. leachi were present on 14 dogs and of R. sanguineus on 172 dogs. Small numbers of Amblyomma hebraeum, R. appendiciulatus, R. evertsi evertsi and R. simus were also collected. The predominance of R. sanguitneus accounts for the high prevalence of canine ehrlichiosis (Ehrlichia canis) within the survey region, compared to canine babesiosis (Babesia canis), which is transmitted by H. leachi, and is a much rarer disease. PMID- 11205168 TI - Survey of canine babesiosis in South Africa. AB - A questionnaire, designed to obtain qualitative information on a number of variables concerning canine babesiosis (biliary fever) in South Africa, was sent to 510 veterinary practices in late 1993. Of the 157 practices that responded, all were presented with cases of babesiosis and most were situated in Gauteng, the Western Cape and KwaZulu-Natal. Apart from the Western Cape, a winter rainfall region, the prevalence of babesiosis cases in dogs was highest in summer. Most of the respondent practices treated between 1,000 and 5,000 sick dogs that included 100 to 500 babesiosis cases each year. Respondents identified cerebral babesiosis, enterorrhagia, 'red' or haemoconcentrated babesiosis, acute renal failure and pulmonary babesiosis or 'shock lung', amongst others, as the most prevalent forms of complicated ('atypical') babesiosis. Diminazene, imidocarb and trypan blue were the most popular antibabesials. Trypan blue was most often used in shocked patients, whereas diminazene and imidocarb were preferred when there was a high parasitaemia in the absence of shock. At least 19 antibabesial treatment regimens were used in practices. These comprised the use of single doses of antibabesial drugs; split doses with repeat injections, and combined drug variations, some of which are undesirable due to possible sterilisation of Babesia infection or potential toxicity. Side-effects were most commonly associated with imidocarb use. Ninety-six percent of respondents used supportive treatment (e.g. corticosteroids, vitamins and 'liver support') in all cases of babesiosis. The use of blood transfusion as supportive treatment varied according to practice and severity of the case. Most practices never cross matched blood to be transfused, and transfusion reactions were rare. Diminazene was most frequently incriminated in cases where drug 'resistance' or relapses occurred. Cerebral and 'red' cases resulted in high mortality. Treatment of babesiosis costs the dog-owning public in South Africa more than R20 million each year. Information on the distribution and possible complicating role of Ehrlichia canis was obtained. Development of a vaccine was the first research priority identified. PMID- 11205169 TI - Helicopter-based censusing of domestic dogs in Gauteng Province, South Africa. AB - Decision support in veterinary epidemiology often depends on density estimates of domestic animals. These estimates are usually based on ground surveys of various types. Ground surveys are difficult to undertake in the informal housing settlements that are frequently encountered in developing countries. In addition, they are time-consuming and expensive. In this study, field experience in enumerating wildlife from helicopters was used to count domestic animals in Gauteng Province, South Africa. Data for domestic dogs are analysed for precision and accuracy and the technique evaluated in terms of its value for decision support. PMID- 11205170 TI - The measurement of glucocorticoid concentrations in the serum and faeces of captive African elephants (Loxodonta africana) after ACTH stimulation. AB - Conventionally, the assessment of adrenal responses to stress relies on blood sample collection. However, blood collection from animals is impossible without restraint or immobilisation that influences results. This study was undertaken to validate recently established enzyme immunoassays that measure faecal glucocorticoid metabolites in elephants, and to perform a preliminary investigation into the biological relevance of this non-invasive method for use in assessing the degree of stress in this species. Four juvenile African elephants were injected i.m. with 2.15 mg synthetic adrenocorticotrophic hormone (Synacthen, Novartis, Switzerland). Blood and faecal samples were collected over 4 h and 7 d respectively. Concentrations of serum cortisol and faecal cortisol metabolites were determined using immunoassay. Variability of basal and peak values in blood and faeces was observed among the elephants. After ACTH injection, serum cortisol concentrations increased by 400-700%. An 11 oxoaetiocholanolone enzyme immunoassay (EIA) proved best suited to measure cortisol metabolites (11,17-dioxoandrostanes) when compared to a cortisol and corticosterone EIA in faecal samples. Concentrations of faecal 11,17 dioxoandrostanes increased by 570-1070%, reaching peak levels after 20.0-25.5 h. Greater levels of glucocorticoid metabolites were measured in faecal samples from elephants kept in small enclosures compared to levels in the faeces of animals ranging over a larger area. The results of this preliminary study suggest that non-invasive faecal monitoring of glucocorticoid metabolites is useful in investigating adrenal activity in African elephants. PMID- 11205172 TI - Bovine mastitis therapy and why it fails. AB - Treatment of bovine mastitis depends on the cause, the clinical manifestation and the antibiotic susceptibility of the agent. Mastitis therapy is commonly unsuccessful owing to pathological changes that occur in the udder parenchyma as a result of the inflammatory reaction to mastitogenic bacteria, pharmacokinetic properties of antimicrobial mastitis drugs, mastitogenic bacterial and related factors, and poor animal husbandry and veterinary interventions. PMID- 11205171 TI - Dirofilaria repens in a cat with acute liver failure. AB - Acute liver failure was diagnosed in a 12-year-old cat. Fine needle aspirate cytology revealed high numbers of unsheathed microfilariae and a hepatocellular reaction with no evidence of bacterial infection. The microfilariae were identified as those of Dirofilaria repens by acid phosphatase staining. The high number of microfilariae seen in both the blood and the liver aspirate samples as well as the favourable response to ivermectin amongst other drugs administered, is suggestive that D. repens was the cause of the liver insult. A positive result obtained with an antigen-capture ELISA (Dirochek) for Dirofilaria immitis antigen was interpreted as false. This is the 1st report of Dirofilaria repens for South Africa. PMID- 11205173 TI - [Hepatitis C]. PMID- 11205174 TI - [Epidemiology and transmission of hepatitic C]. AB - Infections with the hepatitis C virus (HCV) are pandemic, and the WHO estimates a world-wide prevalence of 3%. In Middle Europe approximately 1% of the population are infected, mostly with genotype 1 (85% in Austria). Since the discovery of HCV in 1989 and the introduction of the HCV antibody test in 1990, mainly chronic asymptomatic cases were diagnosed. In developed countries, chronic hepatitis C is the most prominent cause for liver cirrhosis, hepatocellular carcinoma, and liver transplantation. In former years, transmission of HCV was predominantly iatrogenic, e.g. by blood transfusions before 1990, blood products such as coagulation factors in hemophiliacs or anti-D-globuline in rhesus incompatibility, parenteral anti-schistosomal treatment in Egypt, contaminated endoscopes or cardiac surgery. Today, sporadic transmission is more prevalent, mostly in drug addicts via needle sharing, and seldom by needle-stick injuries in medical personnel, vertical transmission from mother to baby, tattooing, piercing, or razor sharing. Given the lack of a prophylactic HCV vaccine, preventive measures are very important such as screening of blood products by PCR, use of disposable instruments. or procurement of drug addicts with single use syringes and needles. PMID- 11205175 TI - [Virology of hepatitis C virus]. AB - Hepatitis C virus (HCV) along with hepatitis G virus are members of the hepacivirus genus of the flavi-viridae family to which the flavi- and pestis viruses also belong. The HCV genome has only one ORF which is flanked by a 5' and 3' noncoding region. The ORF encodes for a single polyprotein, which is stepwise cleaved into the 3 structural proteins, core (C), envelope 1 and 2 (E1,2) as well as into 7 non-structural proteins (p7, NS2, NS3, NS4A, NS4B, NS5A, NS5B). The proteolytic active NS3 plays a central role in this processing. Whereas expectations for development of an HCV vaccine are not very optimistic today, there is great hope in new therapeutic possibilities by inhibition of NS3 function. HCV is highly variable. In the liver and serum of a single patient, genetically slightly different virus particles (quasispecies) can be found. Worldwide, hepatitis C virus has been classified into genotypes and subtypes. This differentiation is not only important epidemiologically, but also has biological and therapeutical implications. PMID- 11205176 TI - [Clinical aspects, course and extrahepatic manifestations of hepatitis C]. AB - Hepatitis C virus infection occasionally causes acute icteric hepatitis. However, primary infection is usually asymptomatic. Viral clearance occurs only in 20%; most patients develop a chronic hepatitis, which tends to be hardly symptomatic for many years. The risk of progression to cirrhosis, hepatocellular carcinoma and end-stage liver disease is associated with the severity of histopathological changes, and is increased by additional factors, such as excessive alcohol intake or coinfection with hepatitis B virus and HIV. Immunologically mediated extrahepatic manifestations of hepatitis C, in particular essential mixed cryoglobulinemia, can often be observed. Occasionally, they lead to fatal complications. PMID- 11205177 TI - [Laboratory diagnosis of hepatitis C virus infection]. AB - In Austria, the prevalence of hepatitis C virus infections is 0.7% (17). Exclusion of a putative infection as well as diagnosis and continuous monitoring of HCV-disease produce considerable costs for the health system. How many and which patients with HCV infection will acquire life-threatening complications is by far not clear. Also, the causes for viral persistence and liver-complications remain obscure. For certain, complex interactions of viral and immunological mechanisms will determine the individual outcome of the disease (1). These considerations pose decisive demands on clinical diagnostics for HCV infections to be dealt with in detail: methods for qualitative detection of an infection as well as for analysis of subtypes and for quantitative determination of viral copies; monitoring of therapy; estimation of the progress of the disease and/or efficacy of therapy. PMID- 11205178 TI - [Differential chronic hepatitis diagnosis]. AB - Chronic hepatitis comprises a group of disorders of the liver exhibiting a chronic necroinflammatory process that differs in etiology, clinical course and treatment strategies. A diagnosis of chronic hepatitis is usually made when inflammation and liver cell necrosis persist for longer than 6 months. Clinical manifestations range from asymptomatic patients to those with advanced hepatic failure. Both sexes and all age groups are affected. Chronic hepatitis may emerge as a sequelae of hepatitis C and less often after hepatitis B. Both diseases are treatable and require rapid and exact diagnosis. The differential diagnosis must exclude autoimmune hepatitis, chronic steatohepatitis, congenital metabolic hepatopathies and drug-induced hepatopathies. Laboratory tests, histologic investigations and clinical differential diagnosis must exclude other causes of chronic liver disease. PMID- 11205179 TI - [Therapy of chronic hepatitis C]. AB - Interferon-alpha is still the only drug with antiviral activity against the hepatitis C virus. However, if the outcome of treatment is measured by highly sensitive virologic test, sustained response rates to interferon monotherapy are low, especially in patients infected with subtype 1 (3-10%). Therefore better therapies are needed. The combination of interferon with ribavirin is a major advance. Although the precise mode of action of ribavirin is unknown, it seems to decrease relapse rates after successful treatment. By combination therapy, 30% of patients with subtype 1 and 65% with subtype 3 had a sustained response. Further improvements can be expected from high-dose induction therapy and from long acting pegylated interferons. Nonresponders may benefit from antifibrotic agents, like long-term interferon therapy, IL-10 or silymarin. PMID- 11205180 TI - A randomised prospective study to evaluate a rapid HIV-antibody assay in the management of cases of percutaneous exposure amongst health care workers. AB - A rapid start of post-exposure prophylaxis with an antiretroviral regime is recommended after percutaneous exposure to blood from an HIV-positive source. Since the HIV-antibody status of the source is usually not known at the time of injury, antiretroviral treatment is started pending the results of HIV testing of the source. A randomised prospective study was designed to compare the use of a rapid-screening assay in the management of cases of percutaneous exposure with the conventional procedure. Prior to the comparative study, the accuracy of a rapid-screening assay performed by non-laboratory trained personnel was evaluated. 123 blinded HIV-positive and HIV-negative samples were correctly identified. In a randomised comparison with the conventional procedure, the application of the rapid-screening assay resulted in a significant reduction of psychological stress, drug use and cost. The estimated net benefit per case was CHF 93.-(62 US$). This study strongly supports the use of the rapid-screening assay in the management of post-exposure prophylaxis for HIV after percutaneous exposure in health care workers. PMID- 11205181 TI - Factors affecting the efficiency of aerosol therapy with pressurised metered-dose inhalers through plastic spacers. AB - AIM: The main objective of this study was to compare the in vitro delivery of salbutamol from a chlorofluorocarbon(CFC)-propelled pressurised metered-dose inhaler (pMDI) versus a newly developed hydrofluoroalkane(HFA)-propelled pMDI through various spacers. In addition, we aimed to study the effect on bronchodilator response when using an optimal pMDI/spacer combination for aerosol delivery compared to a suboptimal combination. METHODS: Particle size distribution and output from salbutamol pMDIs containing either CFC propellants (Ventolin) or HFA propellants (Airomir) were measured using a multistage liquid impinger (MSLI) and compared to that through both detergent-coated (non-static) or untreated (static) large volume (Nebuhaler, Volumatic) and small volume (Aerochamber) plastic spacers. Flow-volume curves (FEV1) were obtained from twelve asthmatic children with known significant bronchodilator response (8 males), aged 13-17 years, randomly inhaling salbutamol from a CFC-pMDI through a static spacer (Nebuhaler) and from an HFA-pMDI through a non-static spacer (Nebuhaler). RESULTS: In vitro output of particles in the respirable range (< 6.8 microns) from HFA-pMDIs was significantly higher than that from CFC-pMDIs using various spacers. Removal of electrostatic charge increased output from CFC- and HFA-pMDIs through all spacers by 17-82%. The mean (SD) bronchodilator response after inhalation of salbutamol from a CFC-pMDI through a static spacer was 7.1% (6.3%) compared to 17.5% (7.9%) after inhalation from an HFA-pMDI through a non static spacer (p = 0.002). CONCLUSIONS: Use of a newly developed HFA-propelled pMDI greatly improves drug delivery through spacers compared to a CFC-propelled pMDI. However, electrostatic charge in plastic spacers remains the key determinant limiting delivery of salbutamol from a pMDI through spacers, and can be reduced by soaking the spacer in a household detergent. Using an optimal pMDI/spacer combination leads to a significantly improved bronchodilator response. PMID- 11205182 TI - Effects of voluntary hyperventilation on glucose, free fatty acids and several glucostatic hormones. AB - BACKGROUND: The aim of the present study was to measure the influence of a defined period of standardised voluntary hyperventilation on the levels of glucose, free fatty acids and several glucose regulating hormones in healthy volunteers. STUDY DESIGN: Eight healthy male subjects were submitted to 20 minutes of controlled hyperventilation and blood levels of glucose, free fatty acids, insulin, glucagon, cortisol, catecholamines and pCO2 were measured before, immediately after and 20 minutes after the end of the hyperventilation period. RESULTS: The hyperventilation led to a significant increase in all above mentioned parameters, except for glucose, where the effect was negligible. CONCLUSIONS: In view of the frequency of accompanying hyperventilation in a great variety of diseases and notably in some intensive care patients we postulate that pitfalls in the interpretation of plasma values of substances involved in glucose metabolism may be avoided by simultaneous determination of arterial pCO2. PMID- 11205183 TI - Myocardial angiogenesis induction with bone protein derived growth factors (animal experiment). AB - Myocardial angiogenesis induction with vascular growth factors constitutes a potential strategy for patients whose coronary artery disease is refractory to conventional treatment. The importance of angiogenesis in bone formation has led to the development of growth factors derived from bovine bone protein. Twelve pigs (mean weight, 73 +/- 3 kg) were chosen for the study. In the first group (n = 6, growth factor group) five 100 micrograms boluses of growth factors derived from bovine bone protein, diluted in Povidone 5%, were injected in the lateral wall of the left ventricle. In the second group (n = 6, control group), the same operation was performed but only the diluting agent was injected. All the animals were sacrificed after 28 days and the vascular density of the left lateral wall (expressed as the number of vascular structures per mm2) as well as the area of blood vessel profiles per myocardial area analysed were determined histologically with a computerised system. The growth factor group had a capillary density which was significantly higher than that of the control group: 12.6 +/- 0.9/mm2 vs 4.8 +/- 0.5/mm2 (p < 0.01). The same holds true for the arteriolar density: 1 +/- 0.2/mm2 vs 0.3 +/- 0.1/mm2 (p < 0.01). The surface ratios of blood vessel profiles per myocardial area were 4900 +/- 800 micron 2/mm2 and 1550 +/- 400 micron 2/mm2 (p < 0.01) respectively. In this experimental model, bovine bone protein derived growth factors induce a significant neovascularisation in healthy myocardium, and appear therefore as promising candidates for therapeutic angiogenesis. PMID- 11205184 TI - Gene therapy of cancer. AB - Gene therapy was initially thought of as a means to correct single gene defects in hereditary disease. In the meantime, cancer has become by far the most important indication for gene therapy in clinical trials. In the foreseeable future, the best way to achieve reasonable intratumoral concentrations of a transgene with available vectors is direct intratumoral injection with or without the aid of various techniques such as endoscopy or CT-guidance. At present, viral and non-viral methods of gene transfer are used either in vivo or ex vivo/in vitro. The most important viral vectors currently in use in clinical trials comprise retroviruses, adenoviruses, adeno-associated viruses, and herpes viruses. None of the available vectors satisfies all the criteria of an ideal gene therapeutic system, and vectors with only minimal residues of their parent viruses ("gutless vectors") as well as completely "synthetic viral vectors" will gain more and more importance in the future. Non-viral gene therapy methods include liposomes, injection of vector-free DNA ("naked DNA"), protein-DNA complexes, delivery by "gene gun," calcium-phosphate precipitation, electroporation, and intracellular microinjection of DNA. The first clinical trial of gene therapy for cancer was performed in 1991 in patients with melanoma, and since then more than 5000 patients have been treated worldwide in more than 400 clinical protocols. With the exception of a case of fatal toxicity in a young man with hereditary liver disease treated intrahepatically with high doses of adenovirus, side effects have been rare and usually mild in all these studies and expression of the transgene could be demonstrated in patients in vivo. However, despite anecdotal reports of therapeutic responses in some patients, unequivocal proof of clinical efficacy is still lacking for most of the varied approaches to gene therapy in humans. As well as our only fragmentary understanding of the molecular pathophysiology of many diseases, the principal reason for the present lack of clinical success of gene therapy is the very low transduction and expression efficiency in vivo of available vectors. Despite the complexities of gene therapy for cancer, the numerous different approaches can be subdivided into three basic concepts: (1) strengthening of the immune response against a tumour, (2) repair of cell cycle defects caused by losses of tumour suppressor genes or inappropriate activation of oncogenes, and (3) suicide gene strategies. In addition, the importance of gene marker studies and gene therapeutic protection of normal tissue are briefly covered in this review. PMID- 11205185 TI - [Image of the month. Mitral valve prolapse]. PMID- 11205186 TI - [Pharma clinics. How I treat...dental emergencies in general practice]. AB - Counselling and drug prescription are the only means for the phycisian to manage dental emergencies. Among these, some are infection related: pulpitis, apical and periodontal abscesses, acute necrotizing ulcerative gingivitis and alveolitis. Urgent medical treatment includes antibiotics, mouth rinses and analgesics except for pulpitis (pain caused by thermal stimuli) for which analgesics alone are prescribed. Infection non related dental emergencies are: hemorrhage for which the best treatment is compression; trauma, mainly dental avulsion for which reimplantation must be done as soon as possible; acute TMD such as open lock which can be reduced by the Nelaton handling. PMID- 11205187 TI - [Clinical case of the month. Unilateral exophthalmos]. AB - This paper describes two cases of unilateral exophtalmos and reviews the diagnostic and therapeutic approach to this clinical entity. PMID- 11205188 TI - [Pneumocystis carinii pneumonia in a child without immunodepression]. AB - We report the case of a 5 1/2 month baby with an atypical pneumonia. The PCR revealed a Pneumocystis carinii pneumonia. The complementary approach failed to show any immunosuppression. We will discuss the aetiology, physiopathology and treatment of Pneumocystis carnii pneumonia, particularly in cases without immunosuppression. We will also recall the importance of this disease in AIDS. PMID- 11205189 TI - [Gitelman syndrome: a rare cause of hypokalemia]. AB - We report a case of hypokaliemia whose origin is a urinary potassium loss associated with syndrome of Gitelman. The syndrome of Gitelman is a rare familiar autosomal recessive nephropathy. We will discuss the pathophysiology of this syndrome and differential diagnoses. PMID- 11205190 TI - [Self instruction, multiple choice questions. Daily management of diabetes in children and adolescents]. AB - The practitioner has usually relatively little experience in the daily management of pediatric diabetes, a complex issue due to multiple factors and individual variability. Seventeen multiple choice questions are proposed, which have been created for an interactive teaching session (see next article). For each question, a single answer is considered to be the most or the only correct one. This answer is given after the questions together with a brief comment about some of the proposed answers. The objective for the reader is self-teaching. The questions are not intended for self-evaluation. PMID- 11205191 TI - [Multiple choice questionnaires: use in electronic group teaching]. AB - Based on a continuing education session on childhood and adolescent diabetes, the strategy of electronic vote system is presented and illustrated using multiple choice questions given in the previous article. PMID- 11205192 TI - [Anorexia nervosa in boys]. AB - Anorexia nervosa is a severe and potentially fatal disorder that generally affects adolescent girls. However, a small number of boys also suffer from anorexia nervosa. Through an analysis of a series of studies and articles, a synthesis of male anorexia nervosa is offered, with emphasis on the differences of the illness between boys and girls. A clinical case is provided as an illustration of this article. PMID- 11205193 TI - [How I investigate...atypical cutaneous mycobacteriosis]. AB - Atypical mycobacterioses affecting the skin are diverse and their treatments are different as well. These diseases show an increasing prevalence. The contamination occurs from the environment while interhuman transmission does not occur. PMID- 11205194 TI - [Meeting report. "MIRACL" study of "Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering"]. AB - The results of the "MIRACL" trial ("Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering") were presented at the recent annual meeting of the American Heart Association in New Orleans last November 2000. This study demonstrates that atorvastatin, at a daily dose of 80 mg starting within the first 24 to 96 hours after an acute coronary event (unstable angina or non-Q-wave acute myocardial infarction) and maintained for 4 months, improves the cardiovascular prognosis by decreasing the combined risk of death (any cause), nonfatal myocardial infarction, resuscitated cardiac arrest and worsening angina with new objective evidence of ischemia requiring urgent hospitalization (-16% versus placebo, p < 0.05). PMID- 11205195 TI - Phase II trial of chronomodulated infusion of 5-fluorouracil and folinic acid in metastatic colorectal cancer. AB - Forty three patients with metastatic colorectal cancer (MCC) received a daily administration of 5-fluorouracil (600 mg/m2/d at the first course, 700 mg/m2/d at the second and 800 mg/m2/d at the third course), and l-folinic acid (150 mg/m2/d) or dl-folinic acid (300 mg/m2/d) both chronomodulated from 22:00 to 10.00 am with peak delivery rate at 4.00 for 5 days every 21 days. Only severe mucositis and diarrhea occurred in 19 courses (5.7% Gr 3; 0.6% Gr 4) in 14 patients. Objective response (OR) was evaluated in 40 patients because of one toxicity and two early progressions. No OR was observed in the 15 previously-treated patients versus 28.5% (8/28) partial responses in chemotherapy naive patients; overall the median survival was 13 months. These results without toxicity and with low OR rate indicate the necessing of a more intensive treatment and confirm the place of oxaliplatin in the chemotherapy of MCC. PMID- 11205196 TI - Serial determinations of aminoterminal propeptide of type III procollagen (PIIINP) and prognosis in ovarian cancer; comparison to CA125. AB - During malignant growth many changes take place in the metabolism of fibrillar type III collagens in the connective tissues. The aminoterminal propeptide of type III procollagen (PIIINP) has been found to be often elevated in ovarian cancer. In the present study the prognostic value of serum PIIINP concentration in epithelial ovarian cancer is evaluated in relation to serum CA125. Fifty-six women were enrolled in the study. Serial venous blood samples were taken preoperatively and 6, 9 and 12 months after operation for PIIINP and CA125 determinations. The results were correlated to the three-year survival. In Kaplan Meier survival analysis the preoperative (P = 0.0422), 9-month (P = 0.0062) and 12-month (P = 0.0062) serum PIIINP concentration distinguished between the patients with good and poor prognosis while CA125 did so only at 9- (P = 0.0005) and 12-month (P < 0.0001) follow-up. In the multivariate analysis the independent predictors of prognosis were the preoperative PIIINP and 12-month CA125 concentrations. The percentage changes in serum PIIINP concentration did not differentiate the patients with good or poor prognosis at any time point, whereas the changes in CA125 concentration significantly divided the patients into two prognostic groups during the second half of the postoperative year. We found that PIIINP and CA125 are complementary to each other as predictors of prognosis in epithelial ovarian cancer as preoperative PIIINP was better than CA125 and 1-year CA125 better than PIIINP in this function. PMID- 11205197 TI - Tissue polypeptide specific antigen (TPS) as a tumor marker in nasopharyngeal carcinoma. AB - Tissue polypeptide specific antigen (TPS) is a new tumor marker that indicates tumor proliferative rate rather than tumor burden. The purpose of this study is to assess the clinical value of TPS in patients with nasopharyngeal carcinoma (NPC). Serum levels of TPS were measured in 60 patients with untreated NPC including 36 squamous cell carcinomas (SCC) and 24 undifferentiated carcinomas. NPC patients were separated into different subgroups based on the International Union Against Cancer (UICC) TNM classification system. Forty three healthy subjects without any evidence of malignancy or other systemic diseases were included as controls. The results showed that (1) the mean serum TPS level of the NPC patients was significantly higher than that of the healthy controls, (2) the mean serum TPS level of NPC patients with SCC was significantly higher than patients with undifferentiated carcinomas, (3) the mean serum TPS levels of NPC patients with higher TNM stages were significantly higher than those with lower TNM stages, (4) the overall diagnostic sensitivity of TPS for NPC is 58.3%, and (5) the overall diagnostic sensitivities of TPS in NPC patients with undifferentiated carcinomas and higher TNM stages were significantly higher than those with SCC and lower TNM stages. In conclusion, our results suggest that TPS may have a potential clinical role as a valuable tumor marker for NPC. PMID- 11205199 TI - HPV testing: where are we now? AB - OBJECTIVES: 1) To assess if HPV (human papillomavirus)-DNA testing using the presently available technology offers any advantage over the utilization of the traditional Pap-smear as a screening tool for women at risk for cervical pre cancers. 2) To assess if the HPV-DNA test is a valuable intermediate triage method for patients with Pap-smears demonstrating ASCUS (Abnormal Squamous Cells of Undetermined Significance) or LG-SIL (Low-Grade Squamous Intraepithelial Lesions) in order to better select those patients who would maximally benefit from colposcopy, thus, using clinical resources in an efficient way. MATERIAL AND METHODS: Review of the peer reviewed literature between 1992 and June 2000 regarding: 1) new and innovative approaches for cervical cancer screening and prevention; 2) advances in management protocols of ASCUS and LG-SIL with the introduction of HPV-DNA test. RESULTS: HPV-DNA testing in association with the Pap (Papanicolau) smear performed either conventionally or, preferably, with the new liquid based cytology is a valuable adjunct with high sensitivity and acceptable specificity rates in defining those patients most likely to demonstrate HG-SIL (High-Grade Squamous Intraepithelial Lesions) at the time of colposcopy. CONCLUSION: At present available evidence indicates that the best reason for performing HPV-DNA testing is the triage of selected patients with ASCUS and in specific settings with LG-SIL. Ongoing clinical studies may demonstrate additional advantages for this technology when used in a screening application. PMID- 11205200 TI - Optimum duration of oral adjuvant chemotherapy of HCFU for colorectal cancer; review of 5-year follow-up. AB - PURPOSE: To investigate the optimal duration of oral HCFU administration for minimization of side effects induced by long-term administration. PATIENTS AND METHODS: In total, 155 patients allocated to two groups of different duration of the therapy were reviewed: twice or three times per day doses of oral HCFU (8 mg/Kg body weight/day) for 3 months vs. 12 months. RESULTS: Though statistically significant difference was not found in cumulative survival and disease-free rates between the groups due to so many violations of duration of therapy, when reanalyzing the variables in order of real duration of therapy, those rates were significantly higher in patients treated for 300 and more days than less than 300 days (g-Wilcoxon test: p < 0.04). No significant difference was observed in the background factors between the groups. CONCLUSION: At least 300 days is suggested to be necessary to obtain the optimal effectiveness of adjuvant chemotherapy for curatively resected colorectal cancer. PMID- 11205198 TI - Importance of 5-fluorouracil dose-intensity in a double randomised trial on adjuvant portal and systemic chemotherapy for Dukes B2 and C colorectal cancer. AB - 366 patients fully resected from a Dukes B2 or C colorectal cancer were randomised to receive 6 courses of systemic chemotherapy comprising either 5 fluorouracil (5 FU) alone (arm A: 450 mg/m2/day-5/21 days) or combined folinic acid (FOL) and 5 FU (arm B: respectively 200 mg/m2 racemic form or 100 mg/m2-l form and 370 mg/m2/day-5/21 days). 173 patients had also been initially randomised to receive one course of intraportal chemotherapy just after surgery or no portal treatment. Oral levamisole (150 mg/day; 3 days every other week) was given to all patients for one year. A significantly higher incidence of leuco granulocytopenia was observed in the arm A (5 FU alone) inducing more frequent dose delays and adaptations as well as levamisole's withdrawal. Then dose intensities and dose-intensity products were lower in this arm but the dose intensity expressed in mg/m2/week remained higher (631 +/- 107 vs 557 +/- 99; p < 0.001). The median follow-up in the study was 4.5 years. Relapse free (RFS) and overall survivals (OAS) were prolonged in the 5 FU alone group peculiarly in those patients who had not been randomised for portal treatment. Curves diverged progressively with longer follows-up (at 8 years; RFS in arm A: 67-71% vs 59-53% in arm B; OAS in arm A: 72-74% vs 56-46% in arm B). Patients suffering from a colon or a Dukes C cancer benefited the most from the treatment with 5 FU alone. The results are discussed in the light of other recent adjuvant trials. Well dosed 5 FU over a short period of time without folinic acid may be a valuable and inexpensive adjuvant treatment for colorectal cancer. Levamisole may no longer be recommended in this setting. PMID- 11205201 TI - Neuroblastoma producing spinal cord compression: rapid relief with low dose of radiation. AB - Symptomatic spinal cord compression requires emergency treatment to alleviate symptoms and to avoid irreversible damage. We describe a successful decompression by low dose radiation to a progressing neuroblastoma in a child. Magnetic resonance imaging post radiation should be performed to assess the response of the tumor to radiation. PMID- 11205202 TI - DNA cytofluorometric analysis of benign and malignant nerve sheath tumors. AB - The present study was undertaken to examine the ploidy patterns of benign and malignant nerve sheath tumors using PI-DNA cytofluorometry and to clarify the relationship between the ploidy patterns and pathological findings for these lesions. The benign nerve sheath tumors (schwannomas and neurofibromas) were found to be dipolid or to be euploid-polyploidization, with a few DNA synthetic cells. The number of polyploid cells increased with increase in the frequency of cells with large and atypical nuclei in histology, regardless of the natures of cellular arrangements. Malignant schwannomas were composed of many polyploid and aneuploid cells with DNA synthetic cells, indicating their active cell proliferation. Thus, benign nerve sheath tumors exhibited low-proliferative ploidy patterns that were clearly different from those of malignant nerve sheath tumors. As Takeshita has already stated, it is difficult to ascertain why some of the neurogenic tumors show euploid-polyploidization (19). Further investigations will be needed in this direction. Finally, it is clear from the results of this study that the cytofluorometric analysis mentioned above is useful for assessing malignancy and that it may be useful for predicting prognosis of nerve sheath tumors. PMID- 11205203 TI - Recurrent intussusception of the sigmoid colon caused by a transanal protruding sessile tubulo-villous malignant polyp. AB - We report a case of a 35 year-old woman with a large malignant sessile tubulo villous polyp of the proximal end of a dolico-sigmoid colon causing intussusception and transanal prolapsing. The diagnosis presented some difficulties being the intussusception intermittent. The clinical feature had been initially misdiagnosed for a very large bleeding polyp (5 cm in size), protruding out of the anus with a long pedicle in the rectum. The histology of multiple bioptic samples of the lesion revealed malignancy. Conventional radiologic studies (plain x-rays, barium enema) after metal clips had been placed on the head of the polyp before it rose up the colon, led to the correct diagnosis without, nevertheless, documenting intussusception. An elective surgical resection of the dolico-sigmoid colon allowed the correct diagnosis and the curative treatment of the colonic intussusception and the malignancy. PMID- 11205204 TI - Clinical behavior of solitary fibrous tumors of the pleura. An immunohistochemical study. AB - Localized fibrous tumors of the pleura are uncommon, generally asymptomatic and usually have a benign behavior even if in a few cases a malignant variant can be observed. We report 11 cases of localized pleural neoplasms submitted to surgical resection during the period 1987-1996. The differentiation between the localized fibrous as well as the less frequent localized malignant mesothelioma has been researched employing cyto-histopathologic and immunohistochemical assays. For the purpose of identifying solitary fibrous tumors of pleura that will behave in malignant manner, we applied the more recent criteria of specific immunohistochemical stains, microvessel density and proliferation mdex. All solitary fibrous tumors resulted positive for Vimentin and negative for Cytokeratin. Among these forms, high cellularity and microvessel density, high expression of Ki 67 and CD31 and negativity of CD34 prognostic factors for a poor prognosis. PMID- 11205205 TI - Immunoregulatory effects of the antitumor polysaccharide lentinan on Th1/Th2 balance in patients with digestive cancers. AB - BACKGROUND: Recent studies demonstrated that patients with advanced cancer may have impaired cell-mediated immunity caused by an imbalance between Th1 and Th2 responses. We evaluated the ability of lentinan (LNT) to modulate Th1 and Th2 responses in patients with digestive cancers. METHODS: Peripheral blood samples were collected preoperatively from 28 patients with digestive cancers before and after intravenous administration of LNT (2 mg x 3 times/week). The proportions of CD4+ T-cells producing intracellular cytokines were determined with flow cytometry. RESULTS: After LNT treatment, CD4+ IFN-gamma+ T-cell percentages increased significantly (p < 0.05), whereas CD4+ IL-4+ T-cell and CD4+ IL-6+ T cell percentages decreased significantly (p < 0.02). No significant change occurred in proportions of CD4+ IL-10+ T-cells. The after/before LNT treatment percentages ratio of CD4+ IFN-gamma+ T-cells correlated negatively with that of CD4+ IL-4+ T-cells (p < 0.01). The after/before treatment percentage ratio of CD4+ IL-4+ T-cells correlated positively with that of CD4+ IL-6+ T-cells (p < 0.05). CONCLUSION: LNT apparently can cancel Th2-dominant condition in patients with digestive cancers and may improve the balance between Th1 and Th2. PMID- 11205206 TI - Radiation and low dose adriamycin for the treatment of carcinoma of the hypopharynx. AB - PURPOSE: To evaluate the utility of adriamycin in radiation therapy for hypopharyngeal cancer. PATIENTS AND METHODS: Forty-five patients with hypopharyngeal carcinoma without distant metastasis were treated. Adriamycin was administered i.v. and weekly (15 mg i.v./once a week, median 64 mg) concurrently with radiation therapy to 38 patients, 76% (34 out of 45) of whom were in an advanced stage (III or IV). RESULTS: Overall survival, cause specific survival and local control rates at 5 years were respectively, 49%, 66% and 69% and better than results obtained in the 1970's. Radiation therapy achieved an 84% (38 out of 45) response rate at 40 Gy. Treatment without voice function loss was attained for 16 patients, consisting of 15 local CR (all T1 and 12 out of 26 T2 tumors) by radical radiation therapy and one posterior wall resection for a T2 tumor. Overall and cause specific survival rates were 57% and 91% at 5 years. Twenty patients who underwent further surgery showed 69% overall and 74% cause specific survival rates. The remaining nine patients, who lost local control, died within 16 months. In 18 patients with T2 cancer originating from the pyriform sinus, 69% local control was obtained for patients using adriamycin compared with 20% for patients without adriamycin (p = 0.17). No severe side effect from the addition of adriamycin has been found so far. CONCLUSIONS: Radiation therapy using low dose adriamycin with or without follow-up surgery is safe and has potential to be a good option. PMID- 11205208 TI - Mismatch repair deficiency in sporadic synchronous colorectal cancer. AB - BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) patients frequently develop synchronous colorectal cancer (SCRC) which also occurs sporadically in other patients. Recent studies on microsatellite instability (MSI) in sporadic SCRC diverge completely in their findings (0%-100%). In the present study MSI and mismatch repair (MMR) proteins were evaluated according to standardised criteria (exclusion of a family history, MSI analysed according to NCI recommendations) METHODS: Paraffin embedded sections of SCRC of 30 patients were evaluated for MSI and the loss of protein expression of hMLH1 and hMSH2. RESULTS: 3 out of 30 (10%) patients exhibited MSI-H which 5 out of 30 (17%) showed MSI-L. Loss of protein expression of either hMLH1 or hMSH2 was found in all cases of MSI-H and none of the MSI-L cancers. CONCLUSION: MSI is found in sporadic cases of SCRC to about the same extent as it is mentioned in the literature on sporadic single colorectal cancers. Immunohistochemistry with mismatch repair proteins could be used as a pre-screening for MMR deficiency in sporadic SCRC. PMID- 11205207 TI - Phase I study of docetaxel administered by bi-weekly infusion to patients with metastatic breast cancer. AB - BACKGROUND: To find a more convenient and tolerable schedule than the tri-weekly or weekly schedules, we conducted a dose escalation study of bi-weekly docetaxel. MATERIALS AND METHODS: Between March 1998 and June 1999, 16 patients entered this phase I study. The starting dose was 40 mg/m2, with planned dose escalation to 45, 50 and 55 mg/m2, in consecutive patient cohorts. Patients continued to receive the assigned treatment at the same dose level bi-weekly, provided that they did not develop progressive disease, refuse further treatment, or experience unacceptable toxicity. RESULTS: Grade 4 neutropenia lasting for more 4 days was seen at dose level 3 in all three patients. Only one patient who had previously received intensive chemotherapy required granulocyte colony stimulating factor (G CSF) to prevent neutropenic fever and there were no actual episodes of neutropenic fever. Grade 3 asthenia and Grade 3 elevation of serum glutamic oxaloacetic transaminase were noted in only one patient treated at a dose of 40 mg/m2. Grade 3 skin toxicity and grade 2 elevation of serum glutamic oxaloacetic transaminase were seen in only one patient treated at a dose of 55 mg/m. Cumulative toxicity was not severe in all patients. Although grade 3 and/or grade 4 neutropenia were noted in eight patients (50%), all except one who received treatment at dose of 55 mg/m2 did not need G-CSF. Nail toxicity and peripheral edema seemed to be related to the number of treatment cycles. Severe fatigue and asthenia were never seen in all patients. CONCLUSION: 1) The maximum-tolerated dose of docetaxel when administered by this bi-weekly schedule was 55 mg/m2; 2) Docetaxel administered on a bi-weekly basis well tolerated. PMID- 11205209 TI - Desmoplastic response in scirrhous gastric carcinoma: imbalance between collagen synthesis and degradation. AB - BACKGROUND: Scirrhous gastric carcinoma is characterized by a marked deposition of collagen in the stroma and has a very poor prognosis. MATERIALS AND METHODS: To elucidate the fibrotic mechanism in scirrhous gastric carcinoma, we measured the activities of the collagen synthetic enzyme, prolyl 4-hydroxylase (P4H) and the collagen degrading enzymes, interstitial collagenase and type IV collagenase, in tissue from patients with advanced gastric carcinoma. Concentrations of P4H and tissue inhibitor of metalloproteinases-1 (TIMP-1) in the sera of patients with gastric carcinoma were measured using sandwich enzyme immunoassay systems. We performed immunohistochemical analysis for TIMP-1. RESULTS: Enzyme activities of P4H, interstitial collagenase and type IV collagenase in the tumor samples of scirrhous gastric carcinoma were significantly lower than those of non-scirrhous gastric carcinoma (p < 0.01). Serum concentration of TIMP-1 in patients with diffuse type carcinoma was significantly higher than in patients with intestinal type carcinoma and control subjects (p < 0.05). We demonstrated stromal expression of TIMP-1 in scirrhous gastric carcinoma tissue. CONCLUSION: These data suggest that decreased collagenase activity and increased expression of TIMP 1 would result in collagen deposition in scirrhous gastric carcinoma tissue. PMID- 11205210 TI - Immunocytochemical detection of circulating esophageal carcinoma cells by immunomagnetic separation. AB - BACKGROUND: Recent developments in detection of micrometastasis have revealed a considerable incidence of systemic disease in patients who would previously have been diagnosed as having solid tumours only. The purpose of this study was to investigate the prevalence and clinical significance of circulating carcinoma cells in patients with esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Peripheral blood samples from 47 primary ESCC patients were enriched by immunomagnetic separation (IMS) using Ber-EP4-conjugated beads (Dynabeads anti epithelial cell) and immunostained with an anti-cytokeratin (anti-CK) antibody. We assayed samples from 12 patients to compare the detection of CK-reactive cells using IMS with the detection of CK 19 mRNA using a reverse transcriptase polymerase chain reaction (RT-PCR) method. RESULTS: CK-reactive cells were observed in 18 out of 47 patients (38%). The detection rate was closely correlated with the stage of disease (TNM stage) (p = 0.0017). In 33 patients who underwent esophagectomy, 4 out of 7 patients (57%) positive for CK cells and only 2 out of 26 patients (7.7%) negative suffered from recurrence in the distant lymph nodes or lungs (p = 0.0108). When IMS and RT-PCR were compared, all 3 samples that were CK-positive by IMS had CK 19 mRNA detected by RT-PCR. However, the other 4 samples with CK 19 mRNA by RT-PCR were negative for CK cells by IMS. Of 7 patients positive for CK-reactive cells before chemotherapy or chemoradiotherapy, 4 patients negative after treatment survived but 3 patients who remained positive died within 6 months. CONCLUSION: Immunocytochemical detection of circulating carcinoma cells by IMS may be a specific method for the diagnosis of systemic disease and for monitoring treatment response. PMID- 11205211 TI - Oral polio vaccine and human cancer: a reassessment of SV40 as a contaminant based upon legal documents. AB - To date, the scientific literature and research examining SV40 and cancer-related diseases has been based upon an assumption that SV40 was not present in any poliovirus vaccine administered in the United States and was removed from the killed polio vaccine by 1963. The basis for this presumption has been that the regulations for live oral polio vaccine required that SV40 be removed from the seeds and monovalent pools ultimately produced in the manufacturing process. The Division of Biologic Standards permitted an additional two tissue culture passages--from three to five--in order to allow manufacturers the ability to remove this contaminant from the oral poliovirus vaccines then awaiting licensure. The confirmation of the removal by one drug manufacturer, Lederle, has been made public at an international symposium in January 1997, where its representatives stated that all of Lederle's seeds had been tested and screened to assure that it was free from SV40 virus. However, in litigation involving the Lederle oral polio vaccine, the manufacturer's internal documents failed to reveal such removal in all of the seeds. The absence of confirmatory testing of the seeds, as well as testimony of a Lederle manager, indicate that this claim of removal of SV40 and the testing for SV40 in all the seeds cannot be fully substantiated. These legal documents and testimony indicate that the scientific community should not be content with prior assumptions that SV40 could not have been in the oral polio vaccine. Only further investigation by outside scientific and independent researchers who can review the test results claimed in the January 1997 meeting and who can conduct their own independent evaluations by testing all the seeds and individual mono-valent pools will assure that SV40 has not been present in commercially sold oral poliovirus vaccine manufactured by Lederle. PMID- 11205212 TI - Sensitivity of serum tumor markers CEA and CA 15-3 in breast cancer recurrences and correlation with different prognostic factors. AB - The aim of this study was to evaluate the correlation between serum tumor markers CEA and CA 15-3 in breast cancer (BC) patients with disease relapse and different prognostic parameters at first operation. Sixty-two women (median age 55 years, range 35-83 years) who had undergone curative surgery for pT1-2 pN0-1 M0 breast cancer developed local recurrences, distant metastases or contralateral BC during a median relapse time of 53 months (range 25-149 months). Sensitivity of CEA, CA 15-3, and CEA + CA 15-3 together was 40.3%, 41.9% and 59.7%, respectively. No correlation (p = NS) was found between tumor markers sensitivity and type of recurrence, surgical procedure, histologic subtypes and hormone receptors rate. CEA significantly (p < 0.01) correlated with the size of the tumor and axillary node status and CA 15-3 with the age of the patients. In conclusion, CEA and CA 15-3 should be considered complementary in detecting BC recurrences but their sensitivity is low and independent of the majority of the prognostic parameters that may be considered before relapse. PMID- 11205213 TI - The use erythrocyte glutathione as a predictive marker for malignant melanoma. AB - BACKGROUND: Glutathione (GSH) may provide defense against reactive oxygen species (ROS) generated by ultraviolet radiation. Furthermore, some authors have demonstrated a relationship between the GSH of peripheral blood erythrocytes (GSHe) and resistance to chemotherapy. PATIENTS & METHODS: To observe the influence of GSH on the genesis and evolution of Malignant Melanoma (MM), we assessed the concentration of GSH in erythrocytes (GSHe) in MM patients (n = 566) and controls (n = 164) by the method of Beutler (1963). RESULTS: No differences were found between the two groups (5.94 +/- 1.61 cases vs 6.08 +/- 1.49 mmol/gr Hb, controls; p > 0.05). Fifty seven patients with poor evolution (disease-free survival < 2 years) had higher GSH levels than the remaining patients (6.35 +/- 1.83 vs 5.83 +/- 1.62 mmol/g Hb; p < 0.01). GSHe increased significantly after antineoplastic therapy (4.75 +/- 1.26 vs 7.73 +/- 1.39 mmoVg Hb; p < 0.001), thus indicating a possible role in chemoresistance. 2 CONCLUSIONS: GSHe is not related to the risk of developing MM. GSHe may be related to the evolution of MM, being higher in patients who suffer relapse or metastasis. GSHe increases significantly during cytostatic treatment. PMID- 11205214 TI - Villous and serrated adenomatous growth bordering carcinomas in inflammatory bowel disease. AB - The histologic phenotype of the dysplastic lesion juxtaposing colorectal carcinomas was assessed in 100 consecutive colectomy specimens: in 50 patients with inflammatory bowel disease (IBD) and in 50 controls (non-IBD patients). Adenomatous growths (AG) were regarded both Dysplasia Associated Lesion or Mass (DALM) and sporadic adenomas. AGs juxtaposing carcinomas were found in 76% (n = 38) of the IBD cases: 52.3% (20 out of 38) were villous, 28.9% (11 out of 38) serrated, 5.3% (2 out of 38) tubular and the remaining 13.2% (5 out of 38) were mixed AGs. Juxtaposing AGs (sporadic adenomas) were also found in 58% (n = 29) of the control cases: 51.7% (15 out of 29) were villous, 6.9% (2 out of 29) tubular, 3.4% (1 out of 9) serrated and the remaining 37.9% (11 out of 29) were mixed. The majority or 81.2% (31 out of 38) of the dysplastic lesions juxtaposing IBD carcinomas were villous or serrated AGs, but only 55.1% (16 out of 29) in control cases. Serrated AGs in particular accounted for nearly 29% of the non-invasive dysplastic lesions abutting IBD carcinomas but only for 3% in control specimens. It would appear that villous and serrated AGs are the most common non-invasive neoplastic lesions from which IBD carcinomas originate. PMID- 11205215 TI - Beta-2-microglobulin (beta 2M) as a tumor marker in nasopharyngeal carcinoma. AB - The purpose of this study was to assess the clinical value of serum beta-2 microglobulin (beta 2M) in patients with nasopharyngeal carcinoma (NPC). beta 2M levels were assayed in 145 Taiwanese patients with untreated NPC, including 100 squamous cell carcinomas (SCC) and 45 undifferentiated carcinomas. The 145 NPC patients were separated into different subgroups based on the International Union Against Cancer (UICC) TNM classification system. In addition, 50 healthy subjects without any evidence of malignancy or other systemic diseases were included as controls. The results showed that (1) the mean serum, beta 2M level of the 145 NPC patients was higher than that of the 50 healthy controls and (2) the mean serum beta 2M levels of NPC patients who were male, older, with SCC, with higher TNM stages, and with a shorter survival time were higher than those patients who were female, younger, with undifferentiated carcinomas, with lower TNM stages, and with a longer survival time. However, none of the differences were significant. In addition, the overall detecting sensitivity of beta 2M for NPC was only 24.1%, and the detecting sensitivities in NPC patients who were male, older, with SCC, with higher TNM stages, and with a shorter survival time were higher than those of patients who were female, younger, with undifferentiated carcinomas, with lower TNM stages, and with a longer survival time. However, these differences also were not significant. In conclusion, our results suggest the beta 2M may have limited clinical potential as a valuable tumor marker for NPC. PMID- 11205216 TI - Serum level of angiogenin in breast cancer. AB - OBJECTIVE: Angiogenin (ANG), a potent inducer of neovascularization, is secreted by some types of human tumor cells and appears crucial for their growth. This study was designed with the aim to investigate any correlation between the serum angiogenin and the clinicopathological variables and furthermore evaluate the prognostic value of serum angiogenin in patients with breast cancer. MATERIAL AND METHODS: Sixty-four consecutive patients with invasive breast cancer undergoing surgery were prospectively included and evaluated. Venous blood samples were collected before surgery. Sera were obtained by centrifugation and stored at -70 degrees C until assayed. The control group consisted of 16 patients with benign breast tumor (8 with fibrocystic disease and 8 with fibroadenoma). Serum concentration of angiogenin was measured by the quantitative sandwich enzyme immunoassay technique. The data on primary tumor staging, age, estrogen receptor, lymph node status, distant metastases and TNM staging were reviewed and recorded. RESULTS: The mean value of serum angiogenin in patients with invasive breast cancer was 2123.95 +/- 324.34 pg/ml and that of control group were 2108.16 +/- 398.20 pg/ml (fibrocystic disease) and 2010.27 +/- 318.40 pg/ml (fibroadenoma). The difference was not significant (p = 0.66). Furthermore, with univariate analysis, there were no significant differences in serum angiogenin levels between the subgroups of the above-mentioned clinicopathological variables. CONCLUSION: Serum angiogenin levels did not appear as a meaningful prognostic parameter for invasive breast cancer. PMID- 11205217 TI - Colorectal cancer trends by anatomic sides, age and staging. A twenty-year study of 1412 Greek cases. AB - The purpose of this study was to investigate whether Greek patients, suffering from colorectal adenocarcinoma, showed the same changes in the side distribution, as has been observed in the patients of many western countries. We retrospectively analysed 1412 consecutive cases of colorectal adenocarcinoma admitted to our institute over in a twenty-year period. The side distribution, the staging and the grade were evaluated in correlation with the age. We found that the number of patients with colorectal adenocarcinoma has steadily increased. The right-sided colonic carcinomas remained stable over the years in the total number of cases, however, for the elderly patients (age > 65 years), there was trend of gradual but steady increase in the incidence. We did not observe any evidence of earlier diagnosis in recent years. We conclude that a delayed but similar trend in the incidence and distribution of colorectal adenocarcinoma is present in Greek patients. The maintenance of the traditional dietary habits could change the pattern. PMID- 11205218 TI - Parameters that influence the outcome of nausea and emesis in cisplatin based chemotherapy. AB - Some factors have demonstrated an influence on emesis and antiemetic response. In order to study these factors, 306 patients (pts) entered this study receiving cisplatin based combination chemotherapy (CT) (100 mg/m3, with ondansetron (8 mg, 3 times daily for 4 days) as the only antiemetic treatment. Known factors that influence the result of antiemetic therapy such as age, sex, performance status (Karnofsky), site of primary tumor, weight loss, anxiety, depression, psychological problems related to CT (psychological PRC) etc, were included in the evaluation. We evaluated the number of vomits, retches and nausea. The existence of psychological PRC was found to be a prominent factor for the development of nausea and emesis, being at the same time strongly associated with scaling variables (Gralla, retching and nausea grading) used to measure the severity of nausea and emesis (p = 0.001). Stress was also a significant predictor; patients with stress had an almost two times higher probability to develop nausea or retching compared to patients without stress indications (p = 0.001), while the occurrence of retching was marginal. Younger patients (less than 40 years old) were found to be almost three times more susceptible to retching compared to older patients (more than 40 years old) (P 0.006). With all possible evaluations, we concluded that significant factors are psychological PRC, stress and age. In conclusion, three factors, age, stress and psychological PRC, should be taken seriously into consideration in the design of future trials evaluating antiemetic treatment, as well as in the every-day clinical practice, in order to provide patients with a better quality of life during emetogenic CT. PMID- 11205219 TI - Whey protein concentrate (WPC) and glutathione modulation in cancer treatment. AB - The glutathione (GSH) antioxidant system is foremost among the cellular protective mechanisms. Depletion of this small molecule is a common consequence of increased formation of reactive oxygen species during increased cellular activities. This phenomenon can occur in the lymphocytes during the development of the immune response and in the muscular cells during strenuous exercise. It is not surprising that so much research has been done, and is still being done on this small tripeptide molecule. Whey protein concentrate has been shown to represent an effective and safe cysteine donor for GSH replenishment during GSH depletion in immune deficiency states. Cysteine is the crucial limiting amino acid for intracellular GSH synthesis. Animal experiments showed that the concentrates of whey proteins also exhibit anti-carcinogenesis and anticancer activity. They do this via their effect on increasing GSH concentration in relevant tissues, and may have anti-tumor effect on low volume of tumor via stimulation of immunity through the GSH pathway. It is considered that oxygen radical generation is frequently a critical step in carcinogenesis, hence the effect of GSH on free radicals as well as carcinogen detoxification, could be important in inhibiting carcinogenesis induced by a number of different mechanisms. Case reports are presented which strongly suggest an anti-tumor effect of a whey protein dietary supplement in some urogenital cancers. This non toxic dietary intervention, which is not based on the principles of current cancer chemotherapy, will hopefully attract the attention of laboratory and clinical oncologists. PMID- 11205221 TI - Long-term survival of a patient with fallopian tube cancer presenting with a supraclavicular mass. AB - BACKGROUND: Five-year survival of patients with stage IV cancer of the fallopian tube is poor. Furthermore, patients with gynecological cancers presenting with a supraclavicular mass generally have an unfavorable prognosis. CASE REPORT: We describe a 70-year-old patient who presented with a left supraclavicular mass. The mass was removed and histology showed metastatic papillary adenocarcinoma strongly suggestive of papillary serous carcinoma. Abdominal hysterectomy and salpingo-oophorectomy showed a primary carcinoma of the fallopian tube. Postoperatively the patient received six cycles of carboplatin-based chemotherapy and is alive and well with no evidence of disease 5 years and 10 months after the primary diagnosis. CONCLUSION: Surgery and adjuvant carboplatin-based chemotherapy seem justified even in older patients with fallopian tube cancer and distant metastasis at the time of diagnosis. PMID- 11205220 TI - p53 status is neither a predictive nor a prognostic variable in patients with advanced ovarian cancer treated with a paclitaxel-based regimen. AB - BACKGROUND: The aim of this study was to assess the relationship between p53 status and the clinical outcome of patients with advanced ovarian cancer treated with a paclitaxel-based regimen. PATIENTS AND METHODS: The investigation was conducted on 38 patients with FIGO stage III-IV ovarian cancer from whom tumor tissue samples for p53 protein immunostaining were obtained during initial cytoreductive surgery. All these patients subsequently received six cycles of first-line combination chemotherapy with paclitaxel 175 mg/m2 (3-hour infusion) plus carboplatin AUC 6 with or without epidoxorubicin 75 mg/m2. RESULTS: Positive p53 immunostaining was detected in tissue samples collected from 24 (63.2%) ovarian cancers. A clinical complete response was obtained in 14 (58.3%) of the 24 patients with positive p53 immunostaining compared to 9 (64.3%) of the 14 patients with negative p53 immunostaining (p = 0.717). A pathological complete response was found in 6 (25.0%) of the former compared to 4 (28.6%) of the latter (p = 0.956). Similarly, survival did not correlate with p53 status (p = 0.1271). DISCUSSION: p53 status seems to be neither a predictive nor a prognostic variable in patients with advanced ovarian cancer treated with a paclitaxel-based regimen. These results are consistent with experimental data showing that paclitaxel cytotoxicity in ovarian cancer is likely to be mediated by a p53-independent pathway. PMID- 11205222 TI - Hibernoma, an uncommon tumor as a differential diagnosis of liposarcoma of the thigh. AB - Hibernomas are benign tumors derived from brown fat of hibernating animals and of human infants. The pathogenesis and malignant potential of hibernomas remain unclear. They occur generally in adults with a peak incidence in the third decade and with a predominance in women. However, the lesions may have an heterogeneous presentation that may mimic liposarcomas on MRI. Our report presents a case of hibernoma of the thigh whose the diagnosis initially suggested that it was a mixed liposarcoma with myxoid and well differentiated components. PMID- 11205223 TI - Ectopic lobular breast cancer of the vulva. AB - BACKGROUND: Primary breast cancer of the vulvar region is a rare tumor entity. Only 12 cases have been published so far in the literature. PATIENT AND METHODS: We report on a case of a 60-year old woman with an invasive lobular breast cancer localized to the vulva. The woman with elevated CA 15-3 and CEA markers underwent local wide excision of the tumor and bilateral inguinal lymphonodectomy, adjuvant anthracycline containing chemotherapy and locoregional irradiation including both inguinal regions and subsequent endocrine therapy with tamoxifen. RESULTS: The resected specimen showed an estrogen receptor-positive diffuse infiltrating lobular breast cancer of the vulva with metastases in both groins. Original tissue of the breast adjacent to the malignant vulvar transformation was lacking. Imaging of the breast was lacking any pathology. Our patient has been followed up for 20 months without any signs of progressive disease. CONCLUSION: Due to the rare occurrence, we are not able to give general guidelines for the treatment of ectopic breast cancer. However, adjustment of treatment to the therapeutic recommendations for orthotopic breast cancer seems reasonable and effective. PMID- 11205224 TI - Expression of multidrug resistance-related markers in gastric cancer. AB - BACKGROUND: To detect the expression of glutathione S-transferase Pi(GST-pi), multidrug resistance-associated protein (MRP), lung-resistance protein(LRP), multidrug resistance gene1 (MDR1) and MGr1 antigen(MGr1-Ag) in the patients with primary gastric cancer and without any prior chemotherapy and to evaluate the correlations between them. PATIENTS AND METHODS: The expression of GST-pi, MRP, LRP and MDR1 in cancer tissue and the adjacent non-cancerous tissue from 50 patients was examined by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). The expression of MGr1-Ag in these tissues was also examined by immunohistochemistry. RESULTS: The positive rate of GST-pi mRNA, MRP mRNA, LRP mRNA, MDR1mRNA and MGr1-Ag in gastric cancer tissue was 36.00%, 12.00%, 10.00%, 10.00% and 18.00% respectively. The overall positive rate of their expression was 58.00%. Clinicopathological factors were not significantly related to their expression. No significant correlation was observed between these markers. CONCLUSION: These MDR markers are differently over-expressed and no coexpression exists in gastric cancer. MGr1-Ag was a novel MDR protein. PMID- 11205225 TI - A new cell proliferating marker: cytosolic thymidine kinase as compared to proliferating cell nuclear antigen in patients with colorectal carcinoma. AB - BACKGROUND: Proliferation markers are necessary for reliable diagnosis. Here we have presented for the first time thymidine kinase 1 (TK1) as a proliferative tumor marker for colorectal carcinoma. PATIENTS AND METHODS: Expression of TK1 in 54 colorectal lesions and 20 colorectal adenoma lesions was detected by immunohistochemistry technique (ABC). Proliferating Cell Nuclear Antigen (PCNA) was run in parallel. RESULTS: TK1-Labelling Index (LI) (65%) was higher than PCNA LI (52%) in the malignant lesions, although not significantly different (p = 0.1717) between them. TK1-LI as well as PCNA-LI showed significant differences between colorectal carcinoma and colorectal adenoma (TK1 p = 0.0005, PCNA p = 0.0005). Both TK1-LI and PCNA were significantly different in respect to tumor stages (TK1 p = 0.0002, PCNA p = 0.0284). However, only TK1-LI showed significant difference in respect to tumor grades (p = 0.014), but not PCNA-LI (p = 0.132). CONCLUSION: TK1-LI showed more potential as a proliferating marker in colorectal carcinoma than PCNA-LI, especially for evaluating high-risk tumor grade and advanced stage in colorectal carcinoma. PMID- 11205226 TI - Transdermal fentanyl in cancer patients with moderate-to-severe pain: a prospective examination. AB - BACKGROUND: [corrected] The aim of the study was to evaluate prospectively the analgesic efficacy, toxicity and acceptability of the transdermal fentanyl therapeutic system (TTS-F) in Greek cancer patients with moderate-to-severe pain. METHODS: Forty-eight patients participated in the study: 34 were men and 14 women, mean age was 63, and all but 2 had advanced stage (IV) cancer. Patients received TTS-F for a period of 8 weeks. Doses ranged from 25 to 225 micrograms/h. Thirty-three patients completed the study. RESULTS: Data indicated statistically significant lower pain scores on both NRS and EORTC QLQ-C30 at all follow-ups compared to baseline. In addition, the vast majority of the patients found the transdermal system easy to use and reported as being satisfied or highly satisfied with it. The only observed side-effect was vomiting. CONCLUSION: In summary, transdermal fentanyl appeared an acceptable, safe and effective method of managing chronic pain induced by malignancies. PMID- 11205227 TI - Epidoxorubicin and paclitaxel as primary chemotherapy for T > 3 cm and T4 breast cancer patients. AB - The Anthracyclines/Taxanes combination is often used in adjuvant and advanced breast cancer. PURPOSE: To evaluate the toxicity and pathological response of sequential epidoxorubicin/paclitaxel combination as primary chemotherapy for T > 3 cm and T4 breast cancer patients. PATIENTS AND METHODS: Forty-eight patients with T2 > 3 cm, T3 and T4 breast tumours were treated with Epidoxorubicin (90 mg/m2, i.v.) on day one and paclitaxel (200 mg/m2 over 3 hours) on day 2 every 21 days for four courses. After the fourth cycle the patients underwent modified radical mastectomy or quadrantectomy plus axillary lymph node dissection followed by six courses of intravenous CMF regimen (days 1 and 8, every 4 weeks). Radiotherapy was given to patients undergoing conservative surgery or with T4 cancers. Tamoxifen was administered in ER or PgR positive patients. RESULTS: Out of the 48 patients enrolled into this trial, 43 were evaluable for toxicity and pathological response. Primary chemotherapy with epidoxorubicin and paclitaxel was well tolerated: no heart toxicity was observed during primary chemotherapy and follow-up. Primary toxicity consisted of myalgia, grade 1 neuropathy and grade 3 alopecia. Disappearance of invasive tumours in the breast with node negative was observed in 11.6% of patients: pathological partial response was shown in 56% of patients. On the whole major pathological response was achieved in 67% of our series: in the remaining 33% we found a stable disease or a size reduction less than 50%. No progressive disease was observed. Conservative surgery was performed in 64.5% of T2 and T3 tumours. CONCLUSION: These preliminary data showed that the epidoxorubicin/paclitaxel combination was safe and effective as primary chemotherapy for patients with T > 3 cm and T4 breast cancer patients. PMID- 11205228 TI - Radiotherapy alone in elderly patients with medically inoperable stage IIIA and IIIB non-small cell lung cancer. AB - BACKGROUND: We have analysed our experience with medically inoperable IIIA and IIIB elderly patients (aged > or = 70 years), treated with radiotherapy alone, to better define the potential benefit of this approach. MATERIALS AND METHODS: From 1992 to 1995, 41 patients with NSCLC (Non Small Cell Lunc Cancer), stage III, aged > or = 70 years were irradiated with curative intent. RESULTS: Median follow up was 20 months (range 9-53). The 2 year OS (Overall Survival) and DFS (Disease Free Survival) were respectively 27% and 14.6% for all patients. Patients presenting weight loss > 10% experienced 14% OS at 24 months compared to 58% for those without weight loss (p = 0.0027). A 64% OS at 24 months was seen in patients with tumor size less than 4 cm compared to 7% of patients with tumor size > 4 cm (p = 0.0009). CONCLUSION: Radiotherapy is a good management for locally advanced NSCLC in the elderly patients assuring good quality of life, high rates of relief of symptoms and OS and DFS similar to those obtained with chemotherapy and chemotherapy plus radiotherapy. PMID- 11205229 TI - Cell cycle-related phosphatases CDC25A and B expression correlates with survival in ovarian cancer patients. AB - Alterations in cell cycle regulating proteins are common in many cancer types. Recent data suggest a possible link between CDC25 phosphatases overexpression and malignancy. Our objective was to evaluate the expression of the three cell cycle related phosphatases CDC25A, CDC25B and CDC25C in patients with ovarian cancer. All the patients had a minimal follow up of three years. CDC25A, CDC25B and CDC25C expression were investigated by immunohistochemistry in 106 patients with ovarian cancer. CDC25A and CDC25B were found expressed in almost all the samples analyzed, while CDC25C was undetectable in more than 80% of the patients. The low evaluable data on CDC25C expression, did not allow any association between the expression of this phosphatase and prognosis. The expression of CDC25A and CDC25B showed some evidences of association with a poor prognosis (p = 0.034 and p = 0.058 respectively). This relationship was independent of other factors such as tumor grade, histotype, stage and residual tumor after surgery. In the same patients the examined parameters (residual tumor, grade, stage and histotype) did show the expected relation with survival. The results indicate that high CDC25A and CDC25B expression is related to a worse prognosis in ovarian cancer patients. CDC25 phosphatases expression can be regarded as a possible prognostic factor for ovarian cancer and these proteins should be evaluated as potential molecular targets of novel drugs against this human neoplasm. PMID- 11205230 TI - Hereditary common cancers: molecular and clinical genetics. AB - This review focuses on the functional role and structural features of the genes involved in common hereditary cancers. Most of these tumors are sporadic and the genetic alterations responsible for their genesis take place over several cell generations; nevertheless, 5 to 10% of the human tumors are hereditary, with a rapid development. Cancer susceptibility genes have been classified as "gatekeepers" (e.g. RB1, ki-ras) and "caretakers" (e.g. hMLH1 and hMSH2, BRCA1). The first step in identifying individuals at high risk of developing a specific inherited form of cancer, and who should therefore undergo genetic tests, is the detailed construction of family history (an accurate cancer family history that includes at least three generation pedigrees, an appropriate cancer risk assessment and an effective genetic counseling). At present, the most useful methods of risk assessment are those performed on the following genes: BRCA1 and BRCA2 especially for hereditary breast and ovarian cancer, hMLH1 and hMSH2 for hereditary non polyposis colorectal cancer, APC for familial adenomatous polyposis, ret for medullary thyroid carcinoma, p53 for the Li-Fraumeni syndrome, p16 for melanoma and RB1 for retinoblastoma. In conclusion, the development of new diagnostic tests will permit a more accurate assessment of risk in individuals who have not so far shown any sign or symptom of the disease. PMID- 11205231 TI - Macrophage infiltration and angiogenesis in endometrial cancer. AB - The aim of this study was to determine whether tumor-associated macrophages (TAMs) infiltration correlates with clinicopathological factors including microvessel, counts and clinical outcome in endometrial cancer. Overall 56 out of the 109 endometrial cancers (51.4%) expressed distinct tumor-associated macrophages infiltration in their tumor stroma. Tumor-associated macrophages infiltration was significantly high in tumors with deep myometrial invasion, high grade and elderly patients. Microvessel counts strongly correlated with tumor associated macrophages infiltration in tumor stroma (p = 0.0002). However, tumor associated macrophages infiltration was not a prognostic factor. In conclusion, tumor-associated macrophages may play a crucial role in the promotion of angiogenesis, but can not be used to prodict prognosis of patients with endometrial cancer. PMID- 11205232 TI - Frequent loss of p16 protein expression and high proliferative activity (Ki-67) in malignant melanoma from black Africans. AB - Malignant melanomas in black Africans are predominantly located on the lower extremities. Since their biological features have not been well focused, we studied 28 such cases with special reference to proliferative activity (Ki-67 expression), p16 and p53 staining, as well as microvessel density, all known to be involved in the progression of melanomas among whites. The findings were related to clinico-pathological characteristics. The tumours had a median thickness of 6.4 mm, ulceration was present in 71%, and vascular invasion in 36%, indicating the presence of advanced and aggressive melanomas. Further, loss of p16 protein expression was found in 50%, and high proliferative activity was present (median 41%). In contrast, strong p53 staining was rare (11%), although most tumours showed low-level positivity. Angiogenesis, as estimated by microvessel density, was significantly associated with vascular invasion (p = 0.022), supporting its role in the progression of these tumours. Thus, our findings indicate that melanomas located on the lower extremities in black Africans show several features of aggressiveness; in particular, the proliferative activity was high, and p16 alterations was frequent as evidenced by loss of protein staining. Our findings also indicated that the diagnosis is delayed among black Africans. PMID- 11205233 TI - Clinicopathological significance of p53 and p21 expression in the surgical treatment of laryngeal carcinoma. AB - BACKGROUND: This study aimed at resolving the clinicopathological significance of p53 and p21 expression in patients undergoing surgical treatment for laryngeal carcinoma. MATERIALS AND METHODS: p53 and p21 expression were studied by immunohistochemical method on surgical specimens of 193 patients. The expressions of p53 and p21 were correlated with the clinicopathological data. RESULTS: Of the 193 tumors, 60% had positive p53 expression and 46% had positive p21 expression. Nodal metastasis was significantly correlated with p53 overexpression, supraglottic involvement and moderate- to poor-differentiation of the tumor. There was significant cumulative effect with increasing risk of nodal metastasis with increasing number of risk factors: 0% without any risk factor, 13% with 1 risk factor, 37% with 2 risk factors and 55% with all 3 risk factors. CONCLUSION: Positive expressions p53 and p21 were common in laryngeal carcinoma. Overexpression of p53 but not p21 was associated with nodal metastasis. The use of p53 expression has added value in providing more accurate prognostic analysis of risk of nodal metastasis in conjunction with site of tumor involvement and tumor grade. PMID- 11205234 TI - A mesocolic leiomyosarcoma metastatic to the breast: case report and review of the literature. AB - This report describes a patient with mesocolic leiomyosarcoma, initially treated by excisional surgery. One year later the patient developed breast and hepatic metastases. To our knowledge, metastasis of leiomyosarcoma to the breast has not been previously reported in the literature. The discussion covers unusual sites for metastases of primary leiomyosarcomas and those tumors that most commonly give rise to breast metastases. Certain rare primary tumors of the breast related to the family of sarcomas are also brought to the attention of the reader. These may or may not have malignant characteristics. In the light of the differences in prognosis and treatment, recognition and precise diagnosis is of importance. PMID- 11205235 TI - Fluorescent location of malignant cells in fine needle aspirates. AB - Malignant cells in fine needle aspirates possess a cell surface protease which can be targeted with fluorescent affinity probes. Cells with active GB exhibit cell surface fluorescence when stained with such affinity probes. The nuclei of all cells on the slides can be counterstained with a nuclear fluorescent stain. Malignant cells are then located by their cell surface fluorescence and their diagnosis confirmed by examining their fluorescent nuclei. Normal cells and benign cells exhibit no cell surface fluorescence and can be ignored. This technique can be used to rapidly select cells of cytological interest in FNA samples obtained routinely and might be adapted for automated screening of FNA. PMID- 11205236 TI - Multiple endocrine neoplasia (MEN)--an overview and case report--patient with sporadic bilateral pheochromocytoma, hyperparathyroidism and marfanoid habitus. AB - The multiple endocrine neoplasia syndromes are divided into two categories: MEN type I and MEN type II. The MEN type II syndrome is further divided into MEN IIa and MEN IIb. The syndromes are characterized by benign and malignant changes in two or more endocrine organs, as well as incidental changes in nervous, muscular and connective tissue. Two main forms can be distinguished: the MEN-I syndrome with hyperplasia of the parathyroid gland, accompanied by islet cell tumor and pituitary adenoma; the MEN-II syndrome with medullary thyroid carcinoma in combination with bilateral pheochromocytoma and hyperplasia of the parathyroid gland (MEN IIa), while type IIb is characterized by the additional appearance of neurocutaneous manifestations without primary hyperparathyroidism. Characteristics shared by these syndromes include the involved cell type, most of the tumors are composed of one or more specific polypeptide- and biogenic amine producing cell types (APUD--amine precursor uptake and decarboxylation). The second characteristic is the increased incidence in certain families. The hereditary component is autosomal dominant with variable expression but high penetrance. Mechanisms of tumorigenesis differ in these syndromes. While MEN I is caused by an inherited mutation of a tumor suppressor gene, menin, located on the long arm of chromosome 11, MEN II is caused by activation of the RET proto oncogene. We have reported the case of a young man exhibiting bilateral pheochromocytoma. In addition, the patient showed mild primary hyperparathyroidism and marfanoid habitus, all these stigmata usually being part of the MEN-II syndrome. Although this described patient showed a phenotypic mixture of the MEN-IIa and MEN-IIb syndrome, the genetic analysis for MEN II and von-Hippel-Lindau gene did not reveal any pathologic mutations, the endocrine disorders described here are not related to multiple endocrine neoplasia syndromes. PMID- 11205237 TI - Disaccordance between estimation of endometrial thickness as measured by transvaginal ultrasound compared with hysteroscopy and directed biopsy in breast cancer patients treated with tamoxifen. AB - OBJECTIVE: To estimate endometrial thickness by transvaginal ultrasound technique (TVU) in patients treated with tamoxifen; and to compare the results with hysteroscopy and directed biopsy, and to relate the findings to curettage material. METHODS: Fifty-four women, over 50 years of age at the time of their primary breast cancer operation and scheduled for adjuvant treatment of tamoxifen, were investigated. If the endometrium measured 8 mm or more (35 patients) hysteroscopy and directed biopsy was performed. RESULTS: In the 35 patients, hysteroscopy and curretage revealed polyps in 18 cases (51.4%), proliferation in 1 case (2.9%) and atrophy in 16 cases (45.7%). In 54.3% (19 cases) of the patients the histopathological finding was a polyp or benign proliferation of the endometrium in agreement with the thickened endometrium seen with TVU. In the remaining 45.7% (16 cases) of the patients a thickened endometrium by transvaginal ultrasound was false positive as the hysteroscopic and subsequent histopathological diagnosis only showed atrofia of the uterine endometrium. CONCLUSIONS: In almost half of the patients the TVU gave a misleading picture concerning the condition of the endometrium. Changes in the myometrium and related connective tissue could be misinterpreted by the ultrasound technique as changes in the endometrium. These results may confirm the theory that stimulation and changes by antiestrogenic treatment of the uterine tissue is not only restricted to the endometrium. In patients with thickened endometrium measured by TVU, a dilatation and curettage is not sufficient, as TVU has not the ability to differentiate between endometrial polyps and myometrial changes. A hysteroscopy and directed biopsy could therefore be performed. PMID- 11205238 TI - Reactive oxygen and nitrogen species: efficient, selective, and interactive signals during intercellular induction of apoptosis. AB - During intercellular induction of apoptosis, transformed fibroblasts are specifically eliminated by their nontransformed neighbours. This potential control step of oncogenesis is based on a sophisticated system of interdependencies and interactions of reactive oxygen and nitrogen species. Activated nontransformed effector cells release a novel peroxidase and nitric oxide. Superoxide anions generated extracellularly by transformed cells participate in intercellular signalling and also determine transformed cells as selective targets for intercellular induction of apoptosis. The interaction of these molecules results in two major signalling pathways, which are based on HOCl/hydroxyl radicals and on NO/peroxynitrite. In addition, involvement of nitrylchloride seems to be conceivable in an alternative pathway. Hydrogenperoxide plays a central and ambivalent role by fostering the HOCl/hydroxyl radical pathway and by inhibiting the NO/peroxynitrite pathway. The interaction of ROS and RNS during intercellular induction of apoptosis seems to represent a general signalling concept utilized by several natural antitumor systems. PMID- 11205239 TI - Altered response to thyroid hormones by breast and ovarian cancer cells. AB - BACKGROUND: In this study, L-thyroxine (T4), 3',3,5-triiodo-L-thyronine (T3), 3,5 diiodo-L-thyronine (T2), reverse T3; 3',5',3-triiodo-L-thyronine (RT3) and transferrin were added to breast cancer cell lines Hs 578T, MDA-MB-231, MDA-MB 468, and T-47D and ovarian cancer cell line OVCAR-3 to test the response to cell proliferation. MATERIALS AND METHODS: Breast and ovarian cancer cell lines were placed in serum-free medium prior to addition of effector. Proliferation was determined by thymidine incorporation. For Northern analysis, RNA was isolated and c-fos, cjun and TIEG expression assessed. RESULTS: No compound provided uniform results across all cell lines. T2 inhibited proliferation in Hs 578T and MDA-MB-468, had no effect in MDA-MB-231 and OVCAR-3, and stimulated proliferation in T-47D cells. T3 inhibited proliferation in all cell lines except T-47D in which two-state behavior occurred, with increased proliferation at low concentrations (< or = 10(-6) M) and decreased proliferation at high concentrations (> or = 10(-5) M). RT3 inhibited proliferation in Hs 578T, MDA-MB 231, and T-47D but had no effect in MDA-MB-468 and OVCAR-3. T4 inhibited proliferation in Hs 578T, MDA-MB-231, and MDA-MB-468 and had two-state behavior in T-47D and OVCAR-3. Finally, transferrin increased proliferation only in OVCAR 3 cells. Protooncogene expression was increased by both transferrin and T4 in the cell lines tested. CONCLUSIONS: Correlation of iodines and proliferative responses were used to determine "essential" iodines necessary to produce the observed effect. Interaction between these cancer cells and non-physiological concentrations of thyroid hormone can be explained by thyroid hormone receptors with altered binding properties. Thus, interaction of thyroid hormones and cancer cells may differ from what occurs with normal cells. PMID- 11205240 TI - TRAG-3, a novel cancer/testis antigen, is overexpressed in the majority of melanoma cell lines and malignant melanoma. AB - BACKGROUND: We have identified a novel cancer/testis antigen, TRAG-3, (Taxol Resistance Associated Gene-3) that was initially discovered in search for new genes involved in drug resistance by differential display. Early study of TRAG-3 revealed minimal to absent expression in various normal tissues and over expression in many carcinoma cell lines including several melanoma lines. MATERIALS AND METHODS: Northern and RT-PCR technologies were used to evaluate TRAG-3 expression in numerous cell lines and tumor tissue. RESULTS: Analysis of a wider panel of normal tissues, 32 melanoma cell lines and 4 malignant melanomas demonstrates TRAG-3 expression in 25 of the 32 melanoma cell lines (78%) and four of four of the malignant melanoma tumors (100%). Of the additional eight normal tissues screened, expression was present in normal testis but absent in all other tissues. RT-PCR evaluation of TRAG-3 reveals two transcripts in many carcinoma cell lines with sequencing of these products demonstrating the 799 bp TRAG-3 transcript and a second alternatively spliced transcript, TRAG-3long TRAG-3 maps to band Xq28 within a MAGE gene complex, however sequence analysis demonstrates that TRAG-3 is not homologous to other known cancer/testis antigens. CONCLUSION: TRAG-3 appears to be a novel cancer/testis antigen. PMID- 11205241 TI - Apurinic/apyrimidinic endonuclease expression in pediatric yolk sac tumors. AB - BACKGROUND: The enzyme apurinic/apyriminidic endonuclease/redox factor 1 (Ape1/ref1), a key protein in the base excision repair pathway, displays repair and redox activity. We examined the role of Ape1/ref1 and a protein it regulates, hypoxia inducible factor 1 alpha (HIF-1 alpha) in pediatric yolk sac tumors. PATIENTS AND METHODS: Using an immunohistochemical evaluation, 16 pediatric yolk sac tumors were evaluated for Ape1/ref1 and HIF-1 alpha expression. Samples were obtained from archival tissue. RESULTS: We demonstrated high levels of expression of Ape1/ref1 in 14/16 of the tumors. This expression was limited to the nucleus of the viable portion of each tumor. High levels of HIF-1 alpha expression was noted in half of the same tumors and localized to both the nucleus and cytoplasm of the viable tumor. CONCLUSIONS: The high levels of expression of Ape1/ref1 in this group of chemosensitive tumors may be related to the subcellular location or redox regulatory activity of one of the other factors controlled by Ape1/ref1. PMID- 11205242 TI - Prostate cancer cell adhesion to quiescent endothelial cells is not mediated by beta-1 integrin subunit. AB - BACKGROUND: Previous studies have reported that tumor cells' adhesion to quiescent endothelial cell is mediated by beta-1 integrins. The aim of this study was to determine the role beta-1 integrins play in prostate cancer cell adhesion to human bone marrow endothelial cells (HBME) and human aortic endothelial cells (HAEC). MATERIALS AND METHODS: A well described blocking antibody to beta-1 integrin subunit was used in adhesion assays to determine the role of beta-1 integrin subunit in the adhesion of PC-3 cells to both HBME cells and HAEC. RESULTS: Antibody to the beta-1 integrin subunit failed to reduce PC-3 adhesion to HBME and HAEC, yet this same antibody significantly reduced adhesion of PC-3 cells to fibronectin coated wells. CONCLUSIONS: The data suggest that metastasis of prostate cancer cells to bone may be mediated, in part, by preferential adhesion to HBME cells; but beta-1 integrins most likely are not involved in this interaction. PMID- 11205243 TI - Perilesional IL-2 treatment of a VX2 head-and-neck cancer model can induce a systemic anti-tumour activity. AB - BACKGROUND: Head-and-neck cancer is associated with impaired cell-mediated immune reactivity. A rabbit model with VX2 Squamous Cell Carcinoma transplanted into both auricles was used to test the effects of a regimen for local Interleukin 2 (IL-2) therapy, optimal in murine tumour models. MATERIALS AND METHODS: Peri tumoural IL-2 treatment started when one of the tumours exceeded 2 cm2 and consisted of 100,000 or 300,000 Chiron Units IL-2 or only solvent during 5 consecutive days. RESULTS: In 4 out of 12 (33%) rabbits the treated primary tumours regressed completely, simultaneously with the non-treated contra-lateral tumours. Also metastases in draining lymph nodes of both treated and untreated primary tumours regressed in three of these animals. Tumour cells injected in the cured animals were rejected. The histology of the regressing tumours in cured cases showed an active granulomatous reaction with a histiocytic response, splitting up of tumour islands, and fibrinoid obstruction of blood vessels. CONCLUSION: These findings showed local and systemic therapeutic effects of this local IL-2 regimen in a VX2 head-and-neck cancer model. PMID- 11205244 TI - Apoptosis induced by inhibitors of nucleotide synthesis in deoxyadenosine resistant leukemia L1210 cells that lack p53 expression. AB - An L1210 cell line (Y8) selected for resistance to deoxyadenosine contains ribonucleotide reductase that is not subject to inhibition by dATP. In addition, the Y8 cells have other phenotypic expressions that include increased sensitivity to apoptosis induced by various agents such as radiation, doxorubicin, anisomycin and roscovitine. The Y8 cells were found to be more sensitive to apoptosis induced by methotrexate (MTX), tiazofurin (TZ), deoxyguanosine (dGuo) and N (phosphonoacetyl)-L-aspartate (PALA). Deoxyguanosine, at concentrations that did not cause apoptosis in the Y8 cells, prevented the apoptotic response of the Y8 cells to MTX and TZ. Deoxycytidine had no effect. Since caspase-3 activation is involved in apoptotic pathways, the effects of the caspase-3 inhibitor, Ac-DEVD CHO, were studied on the dGuo-, MTX- or TZ-induced apoptosis in the Y8 cells. Ac DEVD-CHO caused a marked decrease in the fraction of cells in the early phase of apoptosis. However, there was a corresponding increase in the fraction of cells in the late apoptotic/necrotic stages of cell death. This is in marked contrast to the dGuo-induced decrease in apoptosis seen in the MTX- and TZ-treated Y8 cells in which there were no increases in the late apoptotic/necrotic fraction of cells. These data show that alterations of nucleotide pools in the Y8 cells cause marked increases in the apoptotic response which may indicate that the Y8 cells are much more susceptible to the effects of misincorporation of nucleotides into DNA than are the parental WT L1210 cells. PMID- 11205245 TI - Chemoprevention with triphenylselenonium chloride in selenium-deficient rats. AB - Cancer chemoprevention by high levels of selenium, including compounds like sodium selenite or selenomethionine, is generally not accompanied by increases in known selenoenzymes. There has been no information on whether selenoenzymes are obligatory mediators of the anticarcinogenic effect of selenium. Our previous experience with triphenylselenonium chloride suggests that it might be an ideal agent for studying selenium chemoprevention while simultaneously precluding the synthesis of selenoenzymes. Triphenylselenonium chloride has excellent tumor inhibitory activity but does not support the repletion of selenoenzymes in animals that have been deprived of a bioavailable form of selenium. In the present experiments, we evaluated the efficacy of mammary cancer protection by this compound in rats fed either a selenite-deficient (< 0.01 ppm Se) or selenite adequate (0.1 ppm Se) diet. We also measured the activities of liver glutathione peroxidase and thioredoxin reductase as markers of selenium bioavailability in these different treatment conditions. In carcinogen-treated control animals not receiving triphenylselenonium chloride, mammary tumor incidence and the total number of tumors were similar between the selenite-deficient and selenite adequate groups. Thus the correction of selenium deficiency by the addition of 0.1 ppm Se as selenite did not have detectable anticarcinogenic effects. Supplementation of triphenylselenonium chloride at a level of 30 ppm Se suppressed mammary tumorigenesis by approximately 50% regardless of dietary selenium nutritional status. However, this supplement had little effect on tissue selenium levels and did not increase liver glutathione peroxidase or thioredoxin reductase activities. In contrast, a level of 0.1 ppm Se as selenite did not affect mammary tumorigenesis but markedly increased tissue selenium concentrations and selenoenzyme activities. It is concluded that triphenylselenonium chloride does not release inorganic selenium for selenoprotein synthesis and that its anticancer activity involves mechanisms that are probably intrinsic to the compound. This study also shows for the first time that selenium chemoprevention is possible in an environment of severely depressed selenoenzyme expression. Thus selenium chemoprevention efficacy can be separated experimentally from selenoprotein synthesis using this model system. PMID- 11205247 TI - Cytotoxic activity of steroidal saponins against human oral tumor cell lines. AB - Three steroidal saponins showed higher cytotoxicity against human oral squamous cell carcinoma cell lines (HSC-2), as compared with normal human gingival fibroblasts HGF. Tumor specificity of saponins exceeded that of tannins and flavonoids. Agarose gel electrophoresis showed that saponins failed to induce internucleosomal DNA fragmentation, but produced large DNA fragments in both HSC 2 cells and human promyelocytic leukemic HL-60 cells. In contrast to epigallocatechin gallate or gallic acid, cytotoxic activity of saponins was not significantly affected by metals (Co2+, Cu2+, Fe3+) nor by antioxidants (sodium ascorbate, N-acetyl-L-cysteine, catalase). Furthermore, saponins did not produce radicals (detected by ESR spectroscopy) nor oxidation potential (measured by NO monitor). These data suggest that an oxidation-mediated mechanism is not involved in the cytotoxicity induced by steroidal saponins. PMID- 11205246 TI - Differential effect of camptothecin treatment on topoisomerase II alpha expression in ML-1 and HL-60 leukemia cell lines. AB - Derivatives of camptothecin, an inhibitor of human TOP1, are increasingly being used in treatment of cancers, including leukemia. Sequential combination therapy with inhibitors of TOP2 holds potential promise. Binding of p53 has been shown to inhibit transcription of TOP2 alpha. Down-regulation of TOP2 alpha gene expression by the camptothecin induced DNA damage response may adversely affect the effectiveness of sequential therapy. To address this question, two leukemia cell lines, ML-1 (with wild type p53) and HL-60 (p53 null) were treated with camptothecin to induce similar degree of apoptosis and residual survival. Western blot analysis indicated rapid induction of p53 in ML-1 followed by significant decrease of TOP2 alpha mRNA and protein levels. The expression level of TOP2 alpha in HL60 did not decrease after camptothecin treatment. These results demonstrated that induction of p53 by camptothecin treatment can lead to a decreased level of TOP2 alpha and should be considered in design of combination therapy. PMID- 11205248 TI - Combination of pGL1-TNF-alpha gene and radiation (proton and gamma-ray) therapy against brain tumor. AB - The major goal of this study was to determine if treatment with the newly constructed plasmid vector for tumor necrosis factor-alpha (pGL1-TNF-alpha) could enhance the radiation-induced growth reduction of C6 rat glioma. In addition, two different forms of ionizing radiation (gamma-rays and protons) were utilized. Body and spleen mass, leukocyte blastogenesis, and flow cytometry analysis of cell populations in blood and spleen were performed to detect toxicity, if any, and to identify mechanisms that may correlate with the anti-tumor action of combination therapy. C6 tumor cells were implanted subcutaneously into athymic mice and allowed to become established before treatment initiation. pGL1-TNF alpha was injected into the implanted tumors, which were then irradiated 16-18 hr later; each modality was administered three times over 8-9 days. The addition of pGL1-TNF-alpha significantly enhanced the anti-tumor effect of radiation (p < 0.05). The effect was more than additive, since pGL1-TNF-alpha alone did not slow tumor progression and radiation alone had only a modest effect. Administration of pGL1-TNF-alpha together with proton radiation resulted in tumor volumes that were 23% smaller than those following pGL1-TNF-alpha + gamma-ray treatment; a similar differential in tumor size was observed in the groups receiving only radiation. Body weights and blood and spleen cell analyses did not reveal treatment-related toxicity. High basal proliferation of blood leukocytes and increased B cell levels in the spleen were associated with pGL1-TNF-alpha + 60Co (gamma-radiation) or proton treatment. Overall, the results suggest that the pGL1-TNF alpha/radiation combination is effective and safe under the conditions employed. This is the first study to combine gene and proton radiation therapy and to show, under controlled experimental conditions, that proton radiation may have a greater effect against malignant tumors compared to the same physical dose of gamma-radiation. PMID- 11205249 TI - Evaluation of D-methionine as a cytoprotectant in cisplatin treatment of an animal model for ovarian cancer. AB - BACKGROUND: To evaluate the use of D-methionine(D-met) as a cytoprotectant in the context of clinically relevant doses of cisplatin. MATERIALS AND METHODS: Forty five Fischer rats were injected intraperitoneally with 10(6) NuTu-19 cells and treated as follows: group 1 was the control group and received no treatment, group 2 received cisplatin 4 mg/kg and group 3 received cisplatin 4 mg/kg plus D met. There were two groups that received high dose cisplatin. Group 4 received cisplatin 8 mg/kg and group 5 received cisplatin 8 mg/kg plus D-met. Treatment was initiated four weeks after injection of the NuTu-19 cells, and consisted of four weekly intraperitoneal injections. Serum BUN and creatinine levels in the high dose groups evaluated nephrotoxicity and clinical outcome was measured by mean survival using Kaplan Meier analysis. RESULTS: There were no significant elevations in serum BUN or creatinine levels in any of the rats treated with high dose cisplatin. In the animals given cisplatin 8 mg/kg plus D-met, death from toxicity was prevented and all animals completed four treatments. In contrast, only two animals in group 4 (cisplatin 8 mg/kg alone) completed 4 treatments. There was a significant improvement in survival for the animals given D-met. (p = .0001) In all treated groups except for group 4, there was an improvement in survival compared to the control group. When comparing groups 2 and 3 (4 mg/kg +/ D-met), there was a subjective decrease in tumor response for group 3 but mean survival was not statistically different. (91 vs. 81 days; p = 0.07) A comparison of groups 2 and 5 revealed no survival benefit using high dose cisplatin with D met. (91 vs. 79 days; p = 0.10). CONCLUSIONS: Our results indicate that D methionine provides cytoprotection against cisplatin toxicity without significant compromise of antitumor activity. All though D-methionine allowed for significant dose intensification of cisplatin above standard doses, there was no survival advantage noted in this group of animals. The indications for its use in the treatment of ovarian cancer remain to be determined. PMID- 11205250 TI - Cyanoguanidine CHS 828 induces programmed cell death with apoptotic features in human breast cancer cells in vitro. AB - The cyanoguanidine CHS 828 was recently shown to possess potent anti-tumour effects both in vitro and in vivo. The exact mechanism of action of CHS 828 is not known, but recent results have indicated that induction of programmed cell death may be one mechanism by which CHS 828 exerts its anti-tumour effects. To investigate this aspect in more detail, we studied the effect of CHS 828 and the reference compound Taxol beta on programmed cell death in human breast cancer cells in vitro. Both compounds were found to induce DNA fragmentation in the cells. However, microscopic examination of the cells demonstrated that CHS 828 and Taxol triggered different types of cell death. In the CHS 828-treated cultures most cells were found to be Annexin-V positive, indicating that these cells were early apoptotic cells, while no morphological characteristics of classical apoptosis were seen. In contrast, the cells in the Taxol-treated cultures displayed morphological features characteristic of classical apoptotic cells, but no Annexin-V positive cells could be observed. These findings together with the previously reported potent effects of CHS 828 on tumour cells, makes CHS 828 a promising new agent for the treatment of cancer patients. PMID- 11205251 TI - Immunohistochemical expression of Bcl-2 protein in breast lesions: correlation with Bax, p53, Rb, C-erbB-2, EGFR and proliferation indices. AB - Expression of bcl-2 protein was investigated and correlated with Bax, p53 and Rb proteins, c-erbB-2, EGFR and the proliferation indices PCNA, Ki-67 and MIB1 as well as with the conventional clinicopathological parameters in 95 cases for breast cancer tissue and 20 cases of benign hyperplastic lesions. Bcl-2 and Bax proteins immunoreactivity was detected in normal, hyperplastic and neoplastic breast epithelium. Expression of the bcl-2 protein was detected in 40% of carcinomas (> 10% positive neoplastic cells) and 85.2% of the benign hyperplastic lesions. Bax protein expression was detected in 8.1% of the carcinomas and 5.3% in the hyperplastic group. Rb and p53 proteins were detected in 75.5% and 45.5% of carcinomas. No relationship was observed between bcl-2 expression and patient's age, tumour size, tumour type and grade, lymph node status, Rb protein expression and proliferation indices. However, a strong positive relationship was detected between bcl-2 and Bax (p = 0.008), estrogen (ER) (p = 0.007) and progesterone receptors' (PgR) status (p = 0.0003). An inverse correlation with p53 protein (p = 0.004) was detected. Furthermore, a strong correlation was also observed between pRb and p53 (p = 0.001). The results indicate that in breast cancer bcl-2 protein expression may be under hormonal control. Since the expression is bcl-2 protein was inversely correlated with p53 protein expression, we suggest that bcl-2 may be related with favourable outcome in breast cancer. PMID- 11205252 TI - Anti-invasive effect of contortrostatin, a snake venom disintegrin, and TNF-alpha on malignant glioma cells. AB - BACKGROUND: The snake venom disintegrin contortrostatin has been shown to bind to integrins alpha IIb beta 3, alpha v beta 3, alpha v beta 5, and alpha 5 beta 1 and to exert an anti-tumor activity in vitro and in vivo. The cytokine TNF-alpha has been demonstrated to have anti-invasive properties in vitro. MATERIALS AND METHODS: The human glioblastoma cell line T98G was treated with controtrostatin or colloidal gold-TNF-alpha (CG-TNF-alpha) alone, or in combination. Vitronectin- and fibronectin-dependent adhesion of untreated and treated glioma cells was studied and compared. Invasion through a reconstituted basement membrane (Matrigel) was also examined. RESULTS: Although both contortrostatin and CG-TNF alpha inhibited invasion of T98G cells through Matrigel, the mechanism of inhibition appears to be different. Contortrostatin significantly decreased cell adhesion to vitronectin and fibronectin; CG-TNF-alpha did not. Contortrostatin binds to T98G integrins in an RGD-dependent manner, whereas protein kinase C (PKC) appears to be involved in CG-TNF-alpha actions, leading to inhibition of cell invasion. The efficiency of contortrostatin in inhibiting cell invasion was enhanced by combination with CG-TNF-alpha. CONCLUSION: The combined use of contortrostatin and CG-TNF-alpha may have potential for malignant glioma therapy by effectively inhibiting glioma cell invasion. PMID- 11205253 TI - Comparisons of the pharmacokinetics and the leukopenia and thrombocytopenia grade after administration of irinotecan and 5-fluorouracil in combination to rats. AB - BACKGROUND: Irinotecan (CPT-11) has been used recently for the treatment of several cancers in combination with 5-fluorouracil (5-FU). Preliminary data on this combination therapy in humans demonstrated no drug interactions between CPT 11 (or its metabolite, SN-38) and 5-FU however, because there is so little information on the combination, the possibility for an interaction still exists. MATERIAL AND METHODS: CPT-11 and 5-FU were injected intravenously into rats and the pharmacokinetics of CPT-11 and SN-38 and alternations in blood cell count were investigated. RESULTS: In the group of rats administered 5-FU prior to CPT 11, the area under the concentration-time curve (AUC) of CPT-11 was approximately eight-fold larger compared with the group administered CPT-11 prior to 5-FU. On the other hand, the grade of leukocytopenia or thrombocytopenia was not significantly different among the two groups. CONCLUSION: In rats, the conversion of CPT-11 into SN-38 is possibly delayed by prior administration of 5-FU. PMID- 11205254 TI - NF-kappa B does not modulate sensitivity of renal carcinoma cells to TNF alpha related apoptosis-inducing ligand (TRAIL). AB - BACKGROUND: Immune cells express TNF-related apoptosis-inducing ligand (TRAIL) and may play an important role in controlling the growth of renal cancer. For this reason we examined the potential cytotoxic and intracellular signaling effects of TRAIL on several renal cancer cell (RCC) lines. METHODS: Cytotoxicity was determined using an MTS tetrazolium based assay. Death receptor expression was measured by reverse-transcription polymerase chain reaction. Immunoblot analysis was used to measure cFLIP, caspase-8 and phosphorylated JNK and p38. Activation of NF-kappa B was determined by electrophoretic mobility shift assays. RESULTS: Two RCC lines were highly sensitive to TRAIL-induced cell death, two were of intermediate sensitivity, and two were insensitive. Sensitivity to TRAIL stimulated apoptosis did not correlate with expression of death receptors, decoy receptors, or expression of the caspase-8-inhibitory protein cFLIP. Neither activation or inhibition of the NF-kappa B signal transduction pathway protected sensitive cells from TRAIL-induced cell death. CONCLUSIONS: NF-kappa B, although stimulated in these cell lines, does not play a role in the sensitivity of RCC to TRAIL and could play other functions in TRAIL signaling. PMID- 11205255 TI - In vitro antiproliferative activity of a medium-chain triglyceride solution of 1,25-dihydroxyvitamin D3 in HepG2 cells. AB - BACKGROUND: Successful targeted delivery of 1,25-dihydroxyvitamin D3 [1,25-D3] for the treatment of liver cancer would necessitate the use of an appropriate delivery agent. MATERIALS AND METHODS: Using liver cancer cell line HepG2 in culture, we examined, the possibility of using medium-chain triglyceride (MCT) as a solvent for targeted delivery of 1,25-D3. The drug was made up in either the medium or first dissolved in MCT and subsequently diluted in the medium. Cells were exposed for 1 (acute) or 5 days (chronic) to the 2 different formulations of the drug and cell proliferation was measured by [3H]thymidine and cell count methods. RESULTS: In chronic experiments, exposure of cells to the MCT containing formulation of 1,25-D3 led to significantly greater inhibition of cell proliferation. In the acute experiments where, 1 day 1,25-D3 treatment was followed by 4 days of incubation with normal medium (no drug, no MCT), inhibition of proliferation was more than 2 fold greater in cells exposed to the 1,25-D3/MCT preparation. CONCLUSION: These results indicate that, 1,25-D3 dissolved in MCT probably accumulates and then acts as a sustained release drug depot formulation, in which case it may have potential for the regional treatment of liver tumors. PMID- 11205256 TI - Reversal of multidrug resistance of tumor cells. AB - Drug resistance to chemotherapy is rapidly emerging. Resistance to one drug carries over resistance to unrelated anticancer drugs leading to multidrug resistance (MDR). A major factor of MDR is P-glycoprotein (P-gp) mediated ABC transport found in many eukaryotic cells. P-gp acts as a drug eMux pump. The mdr1 gene involved in P-gp 170 protein production is localized in the human chromosome 7 band p2 1.0-21.1. Point mutations after cross-resistance patterns. A variety of stimuli increase the expression of the mdr1 gene: lowered extracellular pH, heat shock, arsenite, cytotoxic agents, anticancer drugs, transfection with oncogenes, HIV-I, and UV-irradiation. An alternative hypothesis to the efflux pump claims that P-gp modifies the intracellular environment to reduce accumulation of anticancer drugs in cancer cells by creating ionic or proton gradients. Chemosensitizers that block P-gp drug extrusion are generally lipid-soluble at physiological pH, possess a basic nitrogen atom and at least two co-planar rings. P-gp blocking does not depend on drug chirality. This opens the way of treating P gp related MDR with chiral versions of drugs relatively harmless in terms of side effects. We believe that resistance modifiers combined with cytostatics will chemotherapeutically be more effective for cancer patients. PMID- 11205257 TI - Antitumour effect of L-2,4 diaminobutyric acid on a hepatoma cell line. AB - Pharmacological treatment of malignant disease is often insufficient highlighting the need for more efficient treatment based on new principles. We have observed that the amino acid analogue diaminobutyric acid (DAB), accumulates in malignant cells apparently without saturation kinetics, leading to hyperosmosis and subsequently to cell lysis. In the first in vitro part of the present study hepatoma cells were incubated with DAB in miniwells in the presence or absence of physiological amino acids. In the in vivo part malignant cells were inoculated into rat liver after laparotomy. The tumour was treated by continuous infusion of DAB via a catheter, the tip of which was placed in the center of the tumour. DAB had a significant antitumour effect both in vitro and in vivo. The principle of action of DAB as an antitumour agent is unique and therefore would be the ideal partner to practically any other cytostatic drug for a combined treatment to achieve a synergistic effect. PMID- 11205258 TI - Induction of apoptosis by JTE-522, a specific cyclooxygenase-2 inhibitor, in human gastric cancer cell lines. AB - An increased expression of cyclooxygenase (COX)-2 has been observed in various cancers including gastric cancer. Although specific COX-2 inhibitors have a chemopreventive effect on colon cancer, their molecular mechanisms remain unclear. To clarify these mechanisms, we investigated the effects of JTE-522, a newly developed COX-2-specific inhibitor, on gastric cancer cell lines (MKN28 and MKN45). The baseline levels of COX-2 expression were higher in MKN45 than in MKN28. JTE-522 obviously suppressed the levels of COX-2 mRNA, COX-2 protein and PGE2 at a dose of 250 microM in both cancer cells. Apoptosis was induced at 24 hours after treatment with JTE-522 (250 microM) in both cancer cells. To determine the mechanisms of apoptosis induction by JTE-522, the time course of the cell cycle and the apoptosis-related protein levels were examined. An increase in the G1 phase and a decrease in the S phase were observed prior to apoptosis. Moreover, an increase of c-myc protein and a decrease of bcl-2 protein were observed in both cells treated with JTE-522. These findings suggested that JTE-522 could induce apoptosis by blocking the cell cycle, enhancing c-myc expression and diminishing bcl-2 expression. JTE-522 also suppressed proliferation activity in both cell lines. These effects of JTE-522 were more dramatic in MKN45 than in MKN28. Since JTE-522 strongly suppresses cell growth by inducing apoptosis in gastric cancer cell lines, it may therefore serve as a chemopreventive agent. PMID- 11205259 TI - Antiproliferative effects of small fruit juices on several cancer cell lines. AB - Juices prepared from small fruits, mainly growing in the northern part of Japan, were studied in an attempt to explore the feasibility of an assay that screens cytotoxic properties. Screening of 43 small fruit juices indicated that Actinidia polygama Maxim., Rosa rugosa Thunb., Vaccinium smallii A. Gray and Sorbus sambucifolia Roem, strongly inhibited the proliferation of all cancer cell lines examined and yet these juices were substantially less cytotoxic toward normal human cell lines. PMID- 11205260 TI - Inhibitory effect of dietary inulin or oligofructose on the development of cancer metastases. AB - The possible influence of continuous dietary treatment with 15% inulin or oligofructose on the development of lung metastases of a transplantable liver tumor in young male C3H mice was investigated. Microscopical examination demonstrated a distinct inhibitory effect of this dietary treatment on the development of lung metastases of this tumor. There were 59% of mice bearing lung metastases in the control group, 36% in the inulin fed group and 35% in the oligofructose fed group. The total number of lung metastases was 37 in the control group, 18 in inulin fed and 6 in oligofructose fed mice. Several possible, mechanisms hypothetically involved in this astonishing inhibition of the development of lung metastases by dietary treatment with inulin or oligofructose are discussed. PMID- 11205261 TI - Polysaccharides extracted from human tubercle bacilli (specific substance of Maruyama) reduces carcinogenesis in murine ulcerative colitis. AB - Polysaccharides extracted from human tubercle bacilli (specific substance of Maruyama) have been clinically applied in patients with malignant diseases in Japan and other countries. It is known that increased colorectal carcinogenesis occurs in patients with ulcerative colitis. The repeated mucosal necrosis regeneration sequence in chronic ulcerative colitis induced with 3 % dextran sulfate sodium led to colorectal carcinogenesis in azoxymethane-pretreated mice. Simultaneously multiple injections with the polysaccharides reduced the increases in thymidylate synthase and thymidine kinase activities and a number of bromodeoxyuridine-incorporated S-phase cells in colorectal tissues resulted in the reduction of tumorous regions with high-grade dysplasia. PMID- 11205262 TI - CD44 expression and MMP-2 secretion by mouse glioma cells: effect of interferon and anti-CD44 antibody. AB - We have previously reported that invasiveness of mouse glioma G-26, which expresses CD44 adhesion molecule, was inhibited in vitro following treatment with anti-CD44 antibody or mouse interferon alpha/beta (MuIFN alpha/beta). Here, we evaluated whether the expression of transmembrane CD44 adhesion molecule and/or secretion of extracellular matrix metalloproteinases (MMPs) were affected when glioma cell invasion was inhibited. Flow cytometric evaluation of CD44 adhesion molecule expression in G-26 glioma using anti-CD44 antibody, confirmed that G-26 cells were CD44+. Following 3-day treatment with MuIFN alpha/beta at 8 x 10(2) or 8 x 10(3) IU/ml of glioma cells, the expression of CD44 was not significantly affected as reflected by CD44+ cell number and fluorescence intensity. The pretreatment of glioma cells for 1 day with anti-CD44 antibody resulted in a 30 60% decrease of CD44 expression. This coincided with significantly (p < 0.05) lower cell activity as judged by MTT assay for mitochondrial activity. The zymographic evaluation of MMP activity in the G-26 glioma cell culture showed a high level of the active form of MMP-2. This level of MMP-2 was decreased following 3 day treatment of G-26 glioma cells with either 8 x 10(2) or 8 x 10(3) IU/ml of MuIFN alpha/beta but only the latter concentration produced statistically significant 55% decrease. However, following a 1 day treatment of G 26 glioma cells with anti-CD44 antibody, the level of active MMP-2 form was not significantly affected. These findings indicate that while the inhibitory effect of IFN on glioma invasion was accompanied by a decreased level of the active form of MMP-2 released extracellularly, the expression of the transmembrane CD44 adhesion molecule was not affected. Conversely, anti-CD44 antibody pretreatment of G-26 glioma, which led to the inhibition of glioma invasion, resulted in decreased CD44 expression and lower cell activity but had no effect on the MMP-2. PMID- 11205264 TI - Thymidine phosphorylase activity in transitional cell cancer: relation to histological parameters and chemosensitivity to fluorouracil-related drugs. AB - BACKGROUND: Thymidine phosphorylase (TdR-Pase) is an essential enzyme for the metabolism of fluorouracil-related drugs and it is also recognized as a potent angiogenic factor. We measured the TdR-Pase activity in human transitional cell cancers (TCCs) of the urinary tract to assess the relationship between TdR-Pase activity and degree of tumor malignancy. Furthermore, we investigated the relationship between TdR-Pase activity and chemosensitivity to fluorouracil related drugs. MATERIALS AND METHODS: Sixty-two TCC tissues and 12 normal bladder tissues were obtained. TdR-Pase activity was measured with the enzyme-linked immunosorbent assay. The in vitro histoculture drug response assay was also performed to investigate tumor sensitivity to 5-fluorouracil (5-FU) and doxifluridine (5'-DFUR). RESULTS: The TdR-Pase activity of TCCs was three-fold higher than that of normal tissues. The TdR-Pase activity increased along with the histological grade, and the TdR-Pase activity of invasive cancers was significantly higher than that of superficial cancers. However, TdR-Pase showed no relationship with the sensitivity to 5-FU or 5'DFUR. CONCLUSION: A high TdR Pase activity in human TCCs was confirmed to predict a high tumor grade and stage. However, the anti-tumor effect of fluorouracil-related drugs was independent of the TdR-Pase activity. PMID- 11205263 TI - Cytotoxic activity of polyprenylalcohols and vitamin K2 derivatives. AB - Cytotoxic activity of 9 polyprenylalcohols and 6 vitamin K2 derivatives (MK-1 to MK-6) with various lengths of prenyl units was investigated. Among these compounds, geranylgeraniol with 4 prenyl units, and MK-2 with 2 prenyl units, showed the highest cytotoxic activity against human oral tumor cell lines (HSC-2, HSG), without induction of internucleosomal DNA fragmentation. Higher molecular weight compounds showed selective cytotoxicity against tumor cell lines than normal human gingival fibroblasts HGF. ESR spectroscopy showed that all polyprenylalcohols did not produce radical, nor scavenged O2- generated by hypoxanthine and xanthine oxidase reaction, and only slightly enhanced the radical intensity of sodium ascorbate. Vitamin K2 derivatives scavenged O2- more efficiently, but did not produce radical (except MK-3) and only slightly modified the ascorbate radical intensity. Cytotoxic activity of these compounds might be affected by the molecular weight, hydrophobicity, van der Waals area and stabilization of hydration of the molecule. PMID- 11205265 TI - Overexpression of p27 protein in human breast cancer correlates with in vitro resistance to doxorubicin and mitomycin C. AB - BACKGROUND: The cycle regulatory protein p27, an inhibitor of cyclin-dependent kinase (CDK), has been attributed a role in resistance to cancer chemotherapy. However, the predictive value of p27 for chemosensitivity of breast cancer is still unclear. We therefore analyzed the in vitro chemosensitivity to a series of anticancer agents in fresh breast cancer specimens and correlated it with the respective expression levels of p27. MATERIALS AND METHODS: The expression of p27 protein was examined immunohistochemically in 119 patients with primary breast cancer. The in vitro chemosensitivity was assessed by the histoculture drug response assay (HDRA) using mitomycin C (MMC), 5-fluorouracil (5-Fu), Doxorubicin (DXR), cisplatin (CDDP) and cyclophosphamide (CPA). RESULTS: Fifty-six (47%) of the 119 patients demonstrated p27 overexpression. The susceptibility of DXR and MMC in tumors with high p27 expression was significantly higher than that in tumors with low p27 expression. CONCLUSION: Immunohistochemical results regarding p27 might be therapeutically useful as an indicator of response to DXR and/or MMC based adjuvant chemotherapy for breast cancer. PMID- 11205266 TI - Biological activity of feijoa peel extracts. AB - Fractionated extracts of Feijoa peels were studied for cytotoxic activity, anti human immunodeficiency virus (HIV) activity and antibacterial activity. Two most cytotoxic fractions A3 of acetone extract and M2 of methanol extract had potent inhibitory activity against Gram-positive and Gram-negative bacteria as well as fungi tested. Fraction A4 of acetone extract showed multidrug resistance (MDR) reversal activity comparable with that of verapamil (positive control). These results indicate the therapeutic value of Feijoa peel extracts as potential antimicrobial and MDR-modulating agents. PMID- 11205267 TI - Inhibition of invasion and lymph node metastasis of gastrointestinal cancer cells by R-94138, a matrix metalloproteinase inhibitor. AB - BACKGROUND: MMPs have been implicated in the process of metastasis. Matlystatin analogue, called R-94138, isolated from Actinomadura atramentaria, has been reported to inhibit the activity of MMP-2 and -9 specifically. In this study, we investigated the effect of R-94138 on the invasive and lymphnodal metastatic ability of gastric cancer cells. MATERIALS AND METHODS: Three gastric cancer cell lines, MKN-28, MKN-45, MKN-74, and two colorectal cancer cell lines, HT-29, and LS174T were used. The invasion ability of these cell lines were assayed with R 94138 at the required concentration in vitro. The In vivo effect of R-94138 on lymphnode metastasis was examined passaged by orthotopic implantation. RESULTS: All cell lines revealed activity of both 72 and 92 kDa forms of MMPs by gelatin zymography. R-94138 significantly inhibited the invasiveness of all of these cells to the extracellular matrix. The number of lymph node metastases and the amount of body weight loss were significantly decreased by intraperitoneal administration of R-94138. CONCLUSION: MMP inhibitor, R-94138, has a possible application in adjunctive therapy for lymph node metastasis in gastric carcinoma. PMID- 11205268 TI - Quercetin-induced apoptosis in the monoblastoid cell line U937 in vitro and the regulation of heat shock proteins expression. AB - Quercetin, a widely distributed plant flavonoid, inhibits the growth of tumor cells and the expression of heat shock proteins. In this study, we examined quercetin-induced apoptosis of U937 cells in vitro and the regulation of heat shock proteins expression. The quercetin-induced apoptosis was demonstrated to be dose- and time-dependent. Flow cytometry analysis revealed that sub-G1 peak appeared at 12 hours, 24 hours and 48 hours respectively when treated with 50 mM of quercetin and at 6 hours, 12 hours, 24 hours and 48 hours with 100 mM of quercetin. Agarose gel electrophoresis demonstrated a typical ladder-like pattern of DNA fragments in the same time intervals with 50 mM of quercetin and at 6 hours only with 100 mM of quercetin. The distribution of DNA contents showed that U937 cells were accumulated mainly at G2/M phase when incubated with 50 mM of quercetin for 24 hours and 48 hours. There was no specific effect on cell cycle distribution at 100 mM of quercetin. On exposure to 100 mM of quercetin, the inhibition of hsp27 and hsp70 expression was observed from 12 hours to 48 hours and 6 hours to 48 hours respectively. The inhibition of hsp90 expression was not found eiyher at 50 mM or 100 mM of quercetin exposure. When incubated with 50 mM of quercetin, there was no inhibitory effect on hsp27, hsp70 and hsp90 expression by the Western blot analysis. These results suggested that it is dependent on the dose and exposure time of quercetin to induce apoptosis of U937 cells in vitro, to affect the cell cycle distribution and to regulate the expression of hsp27 and hsp70. PMID- 11205269 TI - Failure of detection of the tyrosine to histidine substitution at the residue 33 of thymidylate synthase in human colorectal cancer. A preliminary study. AB - Structural changes in the macromolecular targets of pharmacological agents can result in alterations in the efficacy of these agents. In previous studies Berger et al. (1) identified a variant structural form of thymidylate synthase (TS) that is associated with relative resistance to 5-fluoro-2'-deoxyuridine, in a human colonic tumor cell line. They observed that expression of the variant TS, which differs from the normal form by a tyrosine to histidine substitution at residue 33, confers a 4-fold level of drug resistance in mammalian cells, as well as in bacteria. Now we report on the use of RT-PCR techniques to see if that variant TS form could be present in human samples from patients who underwent surgery for primary colorectal cancer and been previously untreated and to try to find relationships between that hypothetical variant TS form and the 5-Fluorouracil treatment. The possible role of Tyr-33 in 5-fluoropyrimidine-mediated inhibition of TS is discussed. PMID- 11205270 TI - The prognostic significance of autoantibodies against dsDNA in patients with colorectal adenocarcinoma. AB - BACKGROUND: The tumors of the gastrointestinal system have been associated with various immune disorders. The goal of this study was to correlate the presence of the anti-dsDNA autoantibodies in the serum of patients with colorectal adenocarcinoma suffering from the prognosis of their disease. PATIENTS AND METHODS: We investigated 55 patients with colorectal adenocarcinoma, 26 patients with benign surgical disease and 40 healthy volunteers for the presence of anti dsDNA autoantibodies pre-operatively and one month post-operatively, with an ELISA technique. RESULTS: The difference of prevalence of anti-dsDNA antibodies between the group of cancer patients and the two control groups was statistically significant (p < 0.001). After a 3-year follow-up, the difference of incidence of the recurrences between the positive and the negative group for anti-dsDNA autoantibodies of the CA patients was statistically significant (P < 0.01). CONCLUSION: The presence of anti-dsDNA autoantibodies in patients with colorectal cancer indicated a better outcome of the course of the disease. PMID- 11205271 TI - N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride) (W-7) causes increases in intracellular free Ca2+ levels in bladder female transitional carcinoma (BFTC) cells. AB - The effect of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride) (W-7), a widely used calmodulin inhibitor, on intracellular free Ca2+ levels ([Ca2+]i) in bladder female transitional cancer (BFTC) cells was examined using fura-2 as a Ca2+ dye. W-7 (10-1000 microM) caused an increase in [Ca2+]i in a concentration-dependent manner with an EC50 of 75 microM. The [Ca2+]i response was composed of an initial rise and a sustained plateau without significant decaying during the measurement of 250 seconds. Extracellular Ca2+ removal dramatically decreased the Ca2+ signals by 50-90%. W-7 (100 microM) failed to induce a [Ca2+]i increase in Ca(2+)-free medium after pretreatment with thapsigargin (1 microM), an endoplasmic reticulum Ca2+ pump inhibitor; conversely, W-7 pretreatment abolished the Ca2+ release induced by thapsigargin. Addition of 3 mM Ca2+ increased [Ca2+]i after preincubation with 100 microM W-7 in Ca(2+)-free medium. W-7-induced Ca2+ release was not altered by inhibiting phospholipase C with 2 microM 1-(6-((17b-3-methoxyestra-1,3,5 (10)-trien-17 yl)amino)hexyl)-1H-pyrrole-2,5-dione) (U73122). Together, this study shows that W 7 caused [Ca2+]i increases in human bladder cancer cells by releasing intracellular Ca2+ from the endoplasmic reticulum and also by causing extracellular Ca2+ influx with the later playing a dominant role. The W-7-induced intracellular Ca2+ release was uncoupled to a prior elevation in intracellular levels of inositol 1,4,5-trisphosphate (IP3). PMID- 11205272 TI - Retinoic acid modulates stem cell factor secretion by human neuroblastoma cell lines. AB - The hemopoietin stem cell factor (SCF) and its receptor c-kit are expressed in some tumoral cells, including neuroblastoma (NB) cells. We have investigated the effect of retinoic acid (RA), one of the most active differentiating agents on human NB cells, on the SCF production by human neuroblastoma cell lines. SCF concentration was determined by immunoenzymatic assay in the supernatants of seven neuroblastoma cell lines. All cell lines except one showed detectable amounts of SCF in the supernatant in basal culture conditions. A progressive increase pattern of the SCF concentration over time, was common to all SCF secreting cell lines, both unstimulated and RA-stimulated. Moreover, after 48 and 72 hours-exposure to RA, SCF concentrations were higher than in the untreated controls (p < 0.01). Membrane SCF mRNA isoform was also detected by reverse transcription polymerase chain reaction. These effects demonstrated that RA, besides inducing neuronal differentiation, enhanced SCF production in neuroblastoma cell lines. PMID- 11205273 TI - Culture conditions modulate cell phenotype and cause selection of subpopulations in PC3 prostate cancer cell line. AB - PC3 cell line contains different cell variants. A first variant grows as spherical multicellular aggregates and shows anchorage-independent growth. A second variant grows as single small rounds and shows anchorage-dependent growth without cell spreading. A third variant, representing the most abundant population, grows as adherent cells. These populations differ in alpha 2 beta 1 and alpha 3 beta 1 integrin expression with low levels in the suspended (S) cells, intermediate in partially adherent (R) cells and high in adherent cells (A). TPA, which up-regulates the expression of beta 1 integrins, increases invasiveness of cells. In addition, PC3 variants differ in MMP9 and uPA secretion and activity. High levels of TIMP1 and PAI1 present in S variant reduce MMP9 and uPA activities, respectively. In conclusion, PC3 cell line shows variants with strong phenotypic heterogeneity reflecting also the in vitro culture condition. Our observations may explain some of the contradictions in the literature. Therefore, the data obtained with this line should be evaluated more carefully, considering morphological and functional characteristics of the possible variants in the cell population. However, this heterogeneity may represent a good model in the study of tumor progression. PMID- 11205275 TI - The constitutive production of colony stimulating factor 1 by invasive human breast cancer cells. AB - Colony Stimulating Factor 1 (CSF-1) and its receptor, the c-fms proto-oncogene product, are expressed in normal and malignant tissues. The many actions of CSF-1 include induction of urokinase-type plasminogen activator (uPA), a serine protease involved in extracellular matrix degradation. To explore the role of CSF 1 in breast cancer progression, we evaluated the expression of CSF-1, c fms, and uPA in human breast cancer cell lines well-characterized for differing degrees of invasive, metastatic capability. The more invasive cell lines expressed elevated levels of CSF-1 by Northern analysis and ELISA. Increased uPA expression was noted in these same cell lines. CSF-1 receptor mRNA transcripts and protein were demonstrable in the different cell lines. These data suggest a role for CSF-1 in the autocrine and paracrine regulation of tumor progression in breast cancer. PMID- 11205274 TI - Modulation of molecular marker expression by induction chemotherapy in locally advanced breast cancer: correlation with the response to therapy and the expression of MDR1 and LRP. AB - PURPOSE: To assess if molecular markers are able to predict the response to induction chemotherapy in locally advanced breast cancer, and if any variation in their expression is associated with the degree of axillary lymph node invasion. METHODS: Between 1995 and 1999, 48 patients with locally advanced breast cancer were submitted to induction chemotherapy at Fundacion Tejerina--Centro de Patologia de la Mama, Madrid, Spain. The patients carried either tumors larger than 5 cm in diameter with clinically positive axillary nodes, T4a or T4b tumors regardless of size, or inflammatory carcinomas. All received between 3 and 6 cycles of CAF standard polychemotherapy (Cyclophosphamide, Doxorubicin and 5 Fluorouracil) with the exception of one patient, who received CMF therapy (Cyclophosphamide, Methotrexate and 5-Fluorouracil), and another one, who received Taxotere-Doxorubicin. After completion of their induction chemotherapy scheme, 1 patient showed a "complete clinical response" (CCR, with disappearance of all clinical and radiological signs of tumor presence), 36 (75.0%) patients showed a "partial response" (PR, > 50%), 10 (20.8%) showed "no response" (NR, < 50%), and finally one progressed under treatment. Core biopsies were performed in all cases prior to treatment for histological diagnosis which allowed for the determination of the following parameters by means of immunohistochemistry: hormone receptors (ER and PR), oncogenes and tumor suppressor genes (c-erb-B2 and p53) and the proliferation marker Ki67. Initial tumor size, histologic and nuclear grade and histologic variety were also included as variables of the study. After chemotherapy, 37 patients were submitted to a rescue mastectomy at our center. The same aforementioned parameters were determined once again on the operative specimen, together with MDR1 expression (using two different antibodies) and LRP expression. As outcome variables, objective response to treatment and the presence of invaded axillary nodes were considered. RESULTS: Only the expression of the proliferation-associated Ki67 antigen, as well as nuclear grade were affected significantly (p < 0.05) by the previous chemotherapeutic treatment. All other studied parameters showed no significant change in expression. More disappointingly, even, none of the studied variables showed any significant power for predicting either an objective response to treatment, or the presence of invaded axillary nodes at surgery. Both outcome end points were also unrelated to each other. Overexpression of the multidrug resistance gene or the LRP gene, finally, showed no correlation whatsoever with the previous response to chemotherapy. CONCLUSION: According to these results, the parameters employed by us are of no practical use for predicting the response to treatment or the presence of invaded nodes at rescue surgery in locally advanced breast cancer. Clinical and surgical assessment remain thus the mainstay of treatment for this group of patients. PMID- 11205276 TI - Encapsulation of vinblastine into new liposome formulations prepared from triticum (wheat germ) lipids and its activity against human leukemic cell lines. AB - Liposomes prepared from lipids isolated from Triticum sp. (wheat germ) were used to investigate the percentage of Vinblastine encapsulation and its retention into liposomes. The wheat germ total lipids (TL) were extracted by the Bligh-Dyer method and the lipid classes have been isolated using chromatographic techniques. The type of lipids and their percentage content have been examined by TLC coupled with an FID (latroscan). Two liposomal formulations, i.e., I and II, with encapsulated vinblastine, and formulation III (empty liposomes) have been prepared by thin film hydration method. The cytotoxic/cytostatic activity of these liposomal formulations have been examined against nine human leukemic cell lines. The results showed that the percentage content of vinblastine into liposomes I and II depended on the lipid composition and it was greater into formulation II (> 90%). The retention of the drug into liposomes was studied and found to be time-dependent at 37 degrees C. For the cytotoxic/cytostatic activity, the parameters GI50, TGI, LC50 were estimated according to the instructions given by the NCI. The results show that formulation III (empty liposomes), exhibited a growth inhibiting activity, against the most tested cell lines. Formulation II showed mean of LC50 at 124.6 nM, mean of TGI at 71.6 nM and mean of GI50 at 30.8 nM. PMID- 11205277 TI - Antiproliferative and anticarcinogenic effects of an aqueous preparation of Abies alba and Viscum album se abies, on a L-1210 malignant cell line and tumor-bearing Wistar rats. AB - Extracts of plants have been widely tested for possible anticarcinogenic properties. In the present study a traditional remedy, consisting of an aqueous extract of mixed parts of the tree Abies alba and its mistletoe Viscum album se abies was tested on benzo(alpha)pyrene(BaP)-induced tumors in Wistar rats and on the L-1210 malignant cell line. Two main groups of male Wistar rats subcutaneously injected by 10 mg of BaP, a dose inducing 100% carcinogenesis, a control group (C-G, 15 rats) and a treatment group(TR-G, 18 rats), were used for the study. Five animals bearing BaP-induced tumors were also tested (TR-1-G). Animals of the TR-G were orally administered with the aqueous extract at doses of 50 ml/kg b.w, from the day of BaP injection and of the TR-1-G, from the 120th day of injection, till death. L-1210 malignant cells in cultivation, were administered with a powder obtained by condensation and lyophilization of the extract, at various concentrations and cytotoxicity was measured by the microculture tetrazolium assay. Autopsy of the rats, revealed metastasis in the lungs of the animals of all groups and the tumors developed were histologically identified as leiomyosarcomas. The results indicated that the extract of the above plants possess anticarcinogenic effects, documented by: a) its antiproliferative effects on L-1210 cells (IC50 = 49.6 +/- 1.4 micrograms/ml), b) the significant prolongation of life and reduction of tumor growth rate of the animals of the TR-G in comparison to the C-G, c) the inhibition by 16.6% of tumor induction in the TR-G and d) the prolongation of life and the necrotic effects of the extract on the tumors of the animals in the TR-1-G. The antiproliferative effects of the Abies alba and Viscum album se abies extract may be due to the lectins and thionins contained in Viscum album, as well as to the monoterpenes contained in Abies alba. Soft tissue tumors sensitive to the extract, are widespread among human organs, even in larynx, and are usually resistant to chemotherapy. PMID- 11205278 TI - Induction of estradiol synthesis by probucol in the adenocarcinoma cells of an ovarian clear cell tumor. AB - BACKGROUND: Clear cell tumor of Mullerian organs have characteristic intracellular structures with numerous small mitochondria, free ribosomes, lamellae of granular endoplasmic reticulum and intracytoplasmic glycogen granules, but synthesize no estrogens under ordinary conditions. MATERIALS AND METHODS: Cells from an ovarian clear cell tumor cultured with 10 micrograms/ml of the antioxidant probucol released more estradiol into the medium than cells cultured without probucol. Immunocytological analysis revealed the predominance of estradiol in the adenocarcinoma cells cultured with probucol. RESULTS: There was no difference in the distribution of low-density lipoprotein receptors in adenocarcinoma cells according to whether they had been cultured with or without probucol. Cytochemical analysis showed that hydroxylation of estrone was accelerated in the adenocarcinoma cells cultured with probucol as compared to the cells cultured without probucol. CONCLUSION: Probucol is thought to have an unknown function in the acceleration of hydroxylation of steroids in some types of cells with estrogen-producing potential. PMID- 11205279 TI - Oolong tea polyphenol extract induces apoptosis in human stomach cancer cells. AB - The exposure of human stomach cancer KATO III cells to oolong tea polyphenol extact [OTPE] containing oolong tea polyphenol trimer [OTP trimer] as a main component, led to both growth inhibition and the induction of apoptosis. Morphological change showing apoptotic bodies was observed in the cells treated with OTPE. The fragmentation by OTPE of DNA to oligonucleosomalsized fragments that are characteristics of apoptosis was observed to be concentration- and time dependent. These data suggest that the growth inhibition by OTPE results from the induction of apoptosis in the KATO III cells. PMID- 11205280 TI - Metallothionein expression prevents apoptosis. II: Evaluation of the role of metallothionein expression on the chemotherapy-induced apoptosis during the treatment of acute leukemia. AB - Metallothioneins (MT) are low molecular weight cysteine-rich proteins, present in a wide variety of eukaryotes. Although their physiological function is not entirely understood, recently it was found that in vitro human MTs (hMTs) expression prevents apoptosis. In the present study, the apoptosis preventing effect of hMTs is evaluated in vivo, in order to correlate the apoptotic effect of chemotherapy during the treatment of acute leukemia with the expression of hMTs. The expression of hMTs was studied immunocytochemically in bone marrow smears and peripheral blood cytocentrifugations of 47 children with acute leukemia at diagnosis and during treatment. Apoptosis was quantitatively studied in peripheral blood samples during the induction therapy. Eighteen cases were found to be positive for hMTs expression at diagnosis and the mean apoptosis curve of these cases showed maximal effect on the second day of treatment, the apoptotic action of chemotherapy being completed on the tenth day. The mean apoptosis curve of the hMTs negative cases (29 cases) showed maximal effect on the first day of treatment and the apoptotic action of chemotherapy was completed on the sixth day. When considering the day on which the maximal apoptotic effect appeared and the day on which the apoptotic action of treatment was completed, the results indicated retardation of the chemotherapy-induced apoptosis dependent on hMTs expression, as a result of resistance to treatment. Furthermore, the study of hMTs expression during treatment, showed that although the apoptotic action of chemotherapy eliminates blast cells, a cell population positive for hMTs survived and increased during treatment, since they were able to escape apoptotic cell death. These findings, indicated that in vivo, hMTs constitute a cellular protective mechanism preventing chemotherapy-induced apoptosis, thus regulating the response of patients to treatment. PMID- 11205281 TI - Prognostic significance of TGF beta 1 and TGF beta 3 in human breast carcinoma. AB - Transforming growth factor beta s (TGF beta s) are multifunctional growth factors which show differential expression both temporally and spatially and exert pleiotropic effects during carcinogenesis. Although all three mammalian isoforms of TGF beta share considerable sequence similarity, they appear to have distinct functions in health and disease, such as embryogenesis, wound healing and tumourigenesis. Much of our knowledge about the relationship between TGF beta s and breast cancer is based on publications on TGF beta 1 but the role of TGF beta 3 in the progression of breast cancer has not been well documented. In the present study, the expression of TGF beta 1 and TGF beta 3 was assessed by immunohistochemistry. Of the 153 invasive breast cancer tissues, TGF beta 1 was expressed strongly in 25 and moderately in 98 cases. The immunoreactivity of TGF beta 3 was comparable with TGF beta 1, which was expressed strongly in 21 and moderately in 104 cases. The two isoforms were coexpressed in 111 (72.5%) tumours and were absent in 16 cases (10%). Immunostaining for TGFb3 but not TGF beta 1 was inversely correlated with overall survival (p = 0.0204). When combined with lymph node involvement, TGFb3 became an even more significant prognostic factor for overall survival (p = 0.0003), i.e. patients with node metastasis and positive TGFb3 expression had a worse prognosis: the risk of death for these patients was thirteen-fold greater than those who had no node involvement. The fact that it has been reported previously that high TGF beta 3 plasma levels in patients with untreated early stage breast cancer were correlated with subsequent lymph node metastasis and it was observed in the present study too, that TGF beta 3 expression in breast tumours was an independent predictor of overall survival, led us to suggest that the simultaneous measurement of TGF beta 3 in plasma and its expression in resected tumour tissues in the same cohort of patients may prove to be an important parameter in assessing tumour progression. PMID- 11205282 TI - Telomerase inhibitors. AB - Telomerase is attracting great interest as a target for anticancer research because telomerase activity is present in most malignant cells, but undetectable in most normal somatic cells. The antisense approach has been widely exploited and directed to telomerase RNA, chiefly the template region. Ribozymes have been less investigated. Agents that stabilize folded G-quadruplex structures also inhibit telomerase. Inhibitory agents from many chemical classes have been identified, many through screening, but their specificity of action is in doubt. A specific inhibitor is expected to immediately inhibit activity but not cell division, produce telomerase shortening over multiple generations, and ultimately produce end-to-end chromosomal fusion and growth arrest. PMID- 11205283 TI - Structure activity relationship of antiproliferative N-acyl-beta-alanine amides. AB - Starting from the antiproliferative N-homofarnesoyl-beta-alanine amide 1 as a lead structure we have demonstrated that the homofarnesoyl residue of 1 can be replaced by several aliphatic and aromatic acyl moieties which offer advantages in terms of availability and stability over the original homofarnesoyl residue. The N-(2,3-dimethylphenyl) aminosulfonylphenyl moiety of 1 turned out to be essential for antiproliferative activity and cannot be replaced without complete loss of activity. PMID- 11205284 TI - Rational design of platinum chemotherapeutic drugs: hydrophobicity increases cytotoxicity. AB - BACKGROUND: Malignant glioma are often resistant to cisplatin. Numerous chemical modifications have been made to overcome this limitation. Analyzing such novel compounds, we previously hypothesized, that hydrophobicity improves the cytotoxicity of NH3 substituted platinum agents. MATERIALS AND METHODS: Testing this hypothesis, we synthesized further eight novel platinum agents, substituting the NH3 groups with various pyridyl ring systems. The cytotoxicity was measured in MTT tests using the cisplatin resistant human U25 1 malignant glioma cell line as a model. Solubility was measured in water using flameless atomic absorption spectroscopy. RESULTS: Cytotoxicity correlated significantly with low water solubility. The relation of cells surviving 72-hours of 1 OuM drug exposure was best described by a logarithmic formula: Surviving cells (% of control) = 6.4 + 38.4 log (water solubility in mg Pt/L) Adding an oximgroup to the aromatic substitute decreased cytotoxicity. CONCLUSIONS: These data confirmed that increased hydophobicity increases cytotoxicity in this group. This might be caused by better cellular penetration, or by shielding of DNA-adducts from repair processes. The data created a further hypothesis: A positive mesomeric effect as characteristic for the oxim-group might decrease DNA binding, a negative mesomeric might improve it. PMID- 11205285 TI - Aspirin enhances multidrug resistance gene 1 expression in human Molt-4 T lymphoma cells. AB - BACKGROUND: We recently found that aspirin induces the expression of P glycoprotein (P-gp), a protein mediating drug resistance, in human prostate cancer cells. The purpose of this study was to evaluate the effect of aspirin on the expression of P-gp in a different human cancer type, i.e., T lymphoma. Furthermore, we analyzed this effect at the level of the gene encoding P-gp, MDR1, and of the transcription factor (NF-IL6), regulating this gene. MATERIALS AND METHODS: NF-IL6 was assayed by the electrophoretic mobility shift assay, MDR1 mRNA was assayed by the reverse transcriptase polymerase chain reaction (RT-PCR), and P-gp was assayed by Western blotting. RESULTS: aspirin, at plasma attainable levels, induced NF-IL6 DNA-binding activity, and increased MDR1 mRNA expression (by up to 140%), as well as the expression of P-gp, in Molt-4 cells. CONCLUSIONS: This study suggests that treatment with aspirin induces a cellular signal culminating in the enhancement of P-gp expression in T lymphoma Molt-4 cells. PMID- 11205286 TI - Interferon-gamma increases IL-6 production in human glioblastoma cell lines. AB - BACKGROUND: Various immunotherapeutical approaches are presently evaluated for their efficacy to eradicate glioma cells. Complicating the concepts, these tumors secrete cytokines which modulate the immune response. MATERIALS & METHODS: We analyzed the influence of interferon gamma (IFN-gamma) on the cytokine production and IFN-gamma receptor expression in T98G and U87-MG human glioma cells. RESULTS: The IFN-gamma receptors were own-regulated after IFN-gamma treatment. Secretion of interleukin-6 (IL-6) protein was elevated by factors of 6.4 in T98G cells and 5.2 in U87-MG. Other cytokines were increased as well, but less constantly: IL-8, and VEGF were elevated significantly only in T98G, but not in U87-MG. Increases of IL-1 beta, IL-1 alpha and TGF beta-2 were only detectable at the mRNA level. TNF was not detectable in any of the cell lines, and TGF-beta, alpha FGF and HG were not influenced by IFN-gamma. CONCLUSION: IL-6 produced by glioma cells in response to IFN-gamma might support immune eradication of glioma cells. PMID- 11205287 TI - Mapping of genetic deletions on the long arm of chromosome 22 in human pancreatic adenocarcinomas. AB - The molecular mechanisms of carcinogenesis in pancreatic cancer are still poorly understood, although the inactivation of tumor suppressor genes at multiple loci is suspected. We investigated the loss of heterozygosity (LOH) on chromosome 22 in pancreatic cancer by means of a PCR-based microsatellite analysis of archival paraffin-embedded histological sections in order to better define deleted region(s) and to test whether the NF-2 gene is involved. Using a panel of thirteen markers that spanned the long arm of chromosome 22, loss of heterozygosity was identified for at least one locus in 37% of investigated pancreatic adenocarcinomas. These deletions are clustered into two separate areas of the chromosome 22--one proximal to the NF-2 gene and one distal. The NF-2 gene itself is not involved. These regions are likely locations of tumor suppressor genes that may contribute to the development of pancreatic cancer. PMID- 11205288 TI - Heat shock protein expression in human gliomas. AB - BACKGROUND: Heat shock proteins (HSP) are cytoprotective, antiapoptotic proteins which may predict clinical prognosis in various types of cancer. Here, we asked whether the differential response to radiochemotherapy and different overall prognosis for astrocytic and oligodendroglial tumours can be accounted for by differences in HSP expression. MATERIAL AND METHODS: We examined aB-crystallin, HSP27, HSP70, HSC70 (HSP73) and HSP90 expression in 44 human gliomas (5 anaplastic and 5 low-grade astrocytomas, 5 anaplastic and 5 low-grade oligodendrogliomas and 24 glioblastomas) by immunohistochemistry. RESULTS: HSP were expressed in the tumour parenchyma of all high-grade and most low-grade gliomas, including oligodendrogliomas. Endothelial cells were more often positive for HSC70 and HSP90, but more often negative for HSP27, in glioblastomas than in the other tumours. HSP were also observed in macrophages/microglial cells, but not in a tumour-specific pattern. CONCLUSION: Different patterns of HSP expression seem not to account for the differential response of these tumours to adjuvant cytotoxic therapy. PMID- 11205289 TI - Restoration of wild-type p53 activity enhances the sensitivity of pleural metastasis to cisplatin through an apoptotic mechanism. AB - We attempted to develop a new strategy of gene transfer in human metastatic cells avoiding viral vectors. We demonstrated the feasibility of the nlsLacZ gene liposome (DOTAP) complex transfection in lung cancer cell lines H358 and Calu-1 carrying homozygous deletion of p53 and in primary cultures of human pleural metastatic tumor cells (n = 10). The efficiency of transfection in pleural cells was high with a mean of 78 +/- 22% (range 40-100%) compared to H358 (30%) and Calu-1 cells (50%). In this study, we report that growth of pC53-SN3-transfected Calu-1 and pleural metastatic cells was greatly suppressed whereas neither liposomes or Neo-gene affected cells growth. We tempted to determine whether restoration of wtp53 increased the chemosensitivity of cells that normally lack p53 expression. The pC53-SN3 transfected cells (H358 and Calu-1) were more sensitive to CDDP than the parental cells by 14 and 1.2 fold, respectively. In addition, the sensitization ratio due to the transfection of wtp53 in pleural cells (n = 6) varied from 1.2 to 6 fold. This sensitization remained even 21 days after transfection and was accompanied by increase of p53 positive cells and of the proportion of apoptotic bodies. In conclusion our results suggested that DOTAP is an efficient vector for mediating gene transfer in pleural metastatic cells offering advantages compared to viral vectors, while tumor suppressor genes such as p53 may be good candidates in combination with conventional therapy with CDDP that could be further developed for their use in local cancer gene therapy. PMID- 11205290 TI - Thymic humoral factor-gamma 2 augments immune cell response and exerts antitumor activity in murine model systems. AB - The immunomodulatory and antimetastatic/antitumor activity of thymic humoral factor-gamma 2 (THF-gamma 2) was evaluated in BALB/c-mice. Daily subcutaneous applications (7 consecutive days, 20, 200 ng of THF-gamma 2 per injection/mouse) upregulated counts of thymocytes and peripheral blood cells in tumor bearing mice. To check the influence of THF-gamma 2 treatment on the growth of experimental metastases, RAW 117 H10 lymphosarcoma cells or L-1 sarcoma cells were intravenously inoculated into BALB/c-mice to establish liver or lung metastases, respectively. Local tumor growth was induced by subcutaneous injection of L-1 sarcoma cells. THF-gamma 2 was subcutaneously administered daily for 7 consecutive days starting 24 hrs after tumor cell challenge. Organ colonization as well as local tumor growth were investigated on day 14 after tumor cell inoculation and demonstrated a statistically significant (p < 0.05) reduction of experimental liver and lung metastases and local tumor growth for THF-gamma 2 treated mice. PMID- 11205291 TI - Up-regulation of cyclin B1 and cdc2 expression during 9-nitrocamptothecin-induced regression of DU145 prostate tumor. AB - BACKGROUND: We investigated changes in the content and subcellular localization of the cell cycle regulators, cyclin B1 and cyclin-dependent kinase cdc2, in human prostate DU145 tumor and cultured cells treated with the anticancer drug 9 nitrocamptothecin (9NC). MATERIALS AND METHODS: Proteins of interest were identified by Western blot methodology using specific antibodies. RESULTS: The cyclin B1 and cdc2 contents were dramatically elevated in biopsies of DU145 tumor regressing upon 9NC-treatment. In vitro, 9NC-induced apoptosis of DU145 cells was associated with up-regulation of expression and nuclear accumulation of cyclin B1 and cdc2. No changes were observed in cyclins A and E and the cyclin-dependent kinase cdk2 in 9NC-treated DU145 tumor and cultured cells. CONCLUSION: 9NC induced apoptosis in DU145 cells in vivo and in vitro is associated with up regulation of expression and nuclear localization of cyclin B1 and cdc2. PMID- 11205292 TI - In vitro screening of antitumour agents for cardiotoxicity by means of isolated mouse left atria. AB - Cardiotoxicity, a side-effect that can occur after treatment with an anticancer drug, has severe clinical implications. Therefore, a model is desired to screen new anticancer drugs or drug combinations for possible cardiotoxic side-effects. In the present study we tested the applicability of the electrically stimulated isolated mouse left atrium model using a wide range of anticancer drugs with known cardiotoxicity. It appeared that the cardiotoxicity observed in our model, i.e. the negative or positive inotropic effects of the drugs on the isolated atrium, corresponded with the observed cardiotoxicity in animals and/or humans. It is therefore concluded that our model can be used to wam for possible cardiotoxic side-effects of anticancer drugs in vivo. PMID- 11205294 TI - Treatment of metastatic hormone-refractory prostate adenocarcinoma (MatLyLu) in Copenhagen rats with micro-osmotic interleukin-2 pumps. AB - BACKGROUND: We studied the influence of interleukin-2 (IL-2) therapy on tumor growth and prevention of metastasis in metastatic, hormone-refractory prostatic carcinoma (PCa) in an animal model orthotopically (ortho) and subcutaneously (s.c.). MATERIALS AND METHODS: 75 juvenile male Copenhagen rats were divided into five groups of 15 rats each. MatLyLu-PCa (MLL) was implanted ortho (n = 30) in 2 groups or s.c. (n = 30) in 2 groups and were treated locally at the tumor site with micro-osmotic pumps. The rats in 2 groups received IL-2 pumps with 36 x 10(6) IU of IL-2 and the rats in 2 other groups were treated with pumps delivering albumin only as a control. The rats in the last group received ortho MLL and s.c. IL-2 (n = 15). Survival time was then monitored. RESULTS: Prostatic tumor was found in all ortho animals. Additionally lymphogenic and pulmonary metastasis was found in all animals. The orthotopic and s.c. IL-2-treated groups showed a statistically significantly increased survival compared with the orthotopic and s.c. albumin-treated groups. When treating the ortho MLL with s.c. IL-2 there was still a statistically significant longer survival than in the control groups. CONCLUSION: IL-2 therapy significantly reduces tumor growth of rats with metastatic, hormone-refractory prostatic cancer MatLyLu. PMID- 11205293 TI - An elevated serum level of transforming growth factor-beta 1 (TGF-beta 1) significantly correlated with lymph node metastasis and poor prognosis in patients with gastric carcinoma. AB - BACKGROUND: Overexpression of transforming growth factor beta s (TGF-beta s), multifunctional polypeptides, have been reported in the tissue of various types of carcinomas, including gastric carcinoma. To our knowledge, serum levels of TGF beta 1 have not previously been examined in patients with gastric carcinoma as a possible indicator of prognosis. METHODS: Preoperative serum levels of TGF-beta 1 were measured in 111 patients with gastric carcinoma by an enzyme-linked immunosorbent assay. RESULTS: An elevated level of TGF-beta 1 was significantly correlated with lymph node metastasis and poor prognosis. Moreover, the preoperative serum levels of TGF-beta 1 in patients with peritoneal recurrence were significantly higher than those in patients both with lymph node recurrence and without recurrence. CONCLUSION: The serum level of TGF-beta 1 might be useful for predicting recurrence patterns and prognosis in patients with gastric carcinoma. PMID- 11205295 TI - Analysis of the DNA mismatch repair proteins expression in malignant melanomas. AB - The importance of properly functioning DNA mismatch repair has been shown in several tumour types both hereditary and sporadic, but not yet in malignant melanomas. The aim of this study was to examine the expression of DNA mismatch repair genes (MLH1, MSH2, PMS1 and PMS2) in primary melanomas and to define their possible prognostic impact in 106 primary melanomas. MLH1 was found in 64 and MSH2 in 61 out of 106 melanomas. PMS1 and PMS2 proteins were present in 69 and 67 tumours, respectively. Loss of the expression of DNA mismatch repair proteins correlated with the increase of Clark levels. Cox regression analysis demonstrated some prognostic significance for PMS1 (forward p = 0.0018 and backward selections p = 0.0277), MLH1 (only forward selection p = 0.0081) and MSH2 (only backward selection p = 0.0115). PMID- 11205297 TI - Magnetic resonance spectroscopy and fluorescence microscopy to investigate mobile lipids in sensitive, resistant and reverting K562 cells and their membranes. AB - The erythroleukaemic K562 cell line and its adriamycin resistant counterpart were used to study resistance, its reversion and their consequences on the levels and localisation of lipids detected in proton nuclear magnetic resonance (NMR) spectra. On whole cells, the mobile lipids giving rise to a NMR signal were significantly decreased in the resistant cells when compared to the sensitive ones; these lipids recovered partially in the reverting cells. According to the spinlattice relaxation times (T1), the lipids detected appeared to be in a similar environment in sensitive and reverting cells. In membrane-enriched fractions, mobile lipid levels were not significantly different in the sensitive and reverting cell lines but decreased in resistant ones. Moreover, lipid droplets stained with a fluorescent Nile red lipophilic probe showed the presence of highly fluorescent particles in the samples in which NMR detected high levels of mobile lipids. These results suggest the participation of cytosolic lipid droplets in NMR signals in drug sensitive and reverting cells and open the question of the relative roles of these droplets and of the membrane lipids in the lipid metabolic pathways associated with drug resistance in cancer cells. PMID- 11205296 TI - Peritoneal mesothelial cells as a significant source of ascitic immunostimulatory protein 90K. AB - The tumor associated antigen 90K is known to possess cytokine-like modulatory properties on the cellular immune system, whereby accessory cells are the primary target of this molecule. In 67 ovarian cancer patients presenting with significant amounts of ascites, immunostimulatory protein 90K was detected in all ascitic fluid samples examined. Furthermore, 90K levels correlated to ascitic s IL-2R content. To elucidate the source of protein 90K in ascitic fluid; its in vitro release was investigated in primary cultured normal human peritoneal mesothelial cells (HPMC). Peritoneal mesothelium was found to produce five-fold more 90K than ovarian cancer cells. Release of protein 90K was significantly increased by treatment with IFN-gamma in both mesothelial and ovarian cancer cells. In contrast neither IL-1 beta nor TNF-alpha treatment consistently influenced the secretion of 90K in either cell type. PMID- 11205298 TI - Angiogenesis and vasodilation in skin warts. Association with HPV infection. AB - BACKGROUND: Angiogenesis is required for tumour growth. Since human papillomavirus (HPV) infection is associated with the development of neoplastic lesions, the aim of this study was to determine the possible association between HPV infection and angiogenesis in benign tumours. MATERIALS AND METHODS: Specimens of skin warts which were either negative for HPV types 1, 2, 3 and 4 (HPV-ve; n = 15), or positive for HPV2 (HPV+ve; n = 19) were compared with normal skin (NS, n = 10). Vascularity and inflammation were assessed in consecutive sections. vWF-positive blood vessels were classified as small or large using a cut-off value of 50 microns diameter. RESULTS: Vascularity values for small vessels increased significantly from NS to HPV-ve warts and from HPV-ve to HPV+ve warts. Large vessels were found only in warts and their abundance was not related to HPV status. No significant association was found between vascularity and inflammation or between vascularity values for small and large vessels. CONCLUSIONS: The development of skin warts is accompanied by angiogenesis and vasodilation and these two processes may be independently regulated. Further increased angiogenesis, but not vasodilation, is associated with the presence of HPV type 2 DNA. PMID- 11205299 TI - TRAIL-R2 is not correlated with p53 status and is rarely mutated in non-small cell lung cancer. AB - BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors play an important role in regulating apoptosis. Recently, it was shown that the expression of TRAIL-R2, also known as KILLER, Trick or DR5, can be induced by either DNA damage or overexpression of a wild-type p53 transgene, suggesting a role for p53 in the death-signaling pathway. Furthermore, mutations in the death domain of TRAIL-R2 were reported in 10.6% of non-small cell lung cancer (NSCLC) patients in a Korean population, suggesting a role for TRAIL-R2 in lung tumorigenesis. MATERIALS AND METHODS: To determine the association between expression of TRAIL-R2 and p53 mutation status in lung cancers, we compared the two events in 20 small-cell lung cancer (SCLC) cell lines, 20 NSCLC cell lines, and 30 primary NSCLC tumors. We also sequenced the death domain of TRAIL-R2 in a total of 100 primary NSCLC. RESULTS: Lack of TRAIL-R2 expression was found in eight of 20 (40%) SCLC cell lines and in eleven of 20 (55%) NSCLC cell lines. Interestingly, in primary NSCLC, TRAIL-R2 was overexpressed in seven (23%) of the 30 tumors tested, and all primary tumors expressed TRAIL-R2. No association was found between the expression status of TRAIL-R2 and p53 mutation status in primary NSCLC tumors, SCLC cell lines or NSCLC cell lines. Further analysis of the death domain of TRAIL-R2 failed to identify any mutation in 100 primary NSCLC tumors. CONCLUSIONS: Our data indicate that the expression profile of TRAIL-R2 is significantly different in lung cancer cell lines and primary tumors, that the expression of TRAIL-R2 is independent from p53 mutation status and that mutations in the death domain of TRAIL-R2 play a minimal role in NSCLCs in white Americans. PMID- 11205300 TI - Effect of amifostine on neuroblastoma during high dose chemotherapy: in vivo and in vitro investigations. AB - Amifostine (Ethyol, WR-2721) has been clinically used in combination with high dose therapy of neuroblastoma stage 4 with melphalan, carboplatin and VP-16 in 14 patients. The amifostine group was compared to a historical control group of 24 comparably-treated patients. There were no significant differences regarding the time of hematological recovery, the duration of hospitalization, the duration of antibiotic treatment and the extent of renal toxicity. However, in contrast to four patients of the control group, no patient in the amifostine group developed such severe mucositis that artificial ventilation became necessary. Pretreatment of neuroblastoma cell lines for 30 minutes with amifostine and the free thiol(WR 1065) did not reduce the cytotoxic effects of melphalan, carboplatin and VP-16. Evidence was obtained that the uptake of the activated thiol could be achieved by a polyamine transporter. Taken together, the data do not support the use of amifostine in high dose chemotherapy of neuroblastoma prior to autologous stem cell transplantation. However, amifostine may be more effective in conventional neuroblastoma therapy where protection of bone marrow stem cells is necessary. PMID- 11205301 TI - SV40 sequences in human osteosarcoma of German origin. AB - Simian virus 40 (SV40) is a dsDNA polyomavirus that induces osteosarcomas and mesotheliomas in hamsters and transforms many types of cells in tissue culture, including human cells. Osteosarcoma is a bone malignancy with multiple molecular lesions underlining progression from normal bone to osteosarcoma. Recent investigations have identified SV40 DNA sequences in osteosarcomas, suggesting that SV40 may contribute to tumor development. However, these studies also demonstrated that geographical differences exist between SV40 and tumor association. Our study analyzed 46 frozen German tumor specimens (42 osteosarcomas and 4 sarcomas initially suspected to be osteosarcomas) for the presence of SV40 DNA sequences by using PCR. Two different primer sets amplifying a 573 bp region of SV40 Tag gene with the complete intron sequence (SV.for 2/SV.rev) and a 172 bp region with no intron sequence (SV.5/SV.6) were used. DNA sequencing analysis verified the results. No SV40 sequences could be detected using the primer set SV.for 2/SV.rev, while 2 out of 42 osteosarcoma specimens and 1 out of 4 poorly-differentiated tumor specimens contained SV40 sequences, using the primer set SV.5/SV.6. From one of these two positive osteosarcomas, multiple tumor biopsies taken at different times during the dissection, including metastasis, tested positive for SV40. These results indicated that in Germany, only rare osteosarcomas can be linked to SV40. These results support previous findings involving geographical differences in the presence of SV40. Finally, the specific detection of SV40 sequences with multiple specimens from one of the two patients and the absence of SV40 sequences in all other samples underscores the specificity and reproducibility of this investigation and ruled out PCR contamination. PMID- 11205302 TI - Effect of iron chelator, hydroxyl radical scavenger and cytochrome P450 inhibitors on the cytotoxicity of cisplatin to tumor cells. AB - BACKGROUND: Iron catalyzed reactive oxygen metabolites (ROM) are important mediators in cisplatin (CP)-induced nephrotoxicity, and cytochrome P450 (CYP) is the major source of this iron. Iron chelators, hydroxyl radical scavengers and CYP inhibitors have shown marked protection. MATERIAL AND METHODS: This study was designed to determine whether these agents affect the tumoricidal efficacy of CP to LLC-WRC 256 tumor cells. RESULTS: CP was cytotoxic to the tumor cells in a dose and time dependent manner. Iron chelator, hydroxyl radical scavenger and CYP inhibitors did not reduce the cytotoxic effect of CP. Exposure of the tumor cells to CP did not increase the catalytic iron release and the generation of hydroxyl radical. Both CYP activity and content in the tumor cells were less than 10% of that in the rat liver. CONCLUSION: We speculate that iron chelator, hydroxyl radical scavenger and CYP inhibitors do not alter the antitumor efficacy of CP. PMID- 11205303 TI - The impact of expression of the metastasis suppressor protein KAI1 on prognosis in invasive squamous cell cervical cancer. AB - OBJECTIVES: Loss of KAI1 protein is a frequent event in various types of cancer and has been reported to be associated with increased rate of metastasis and shorter survival time. METHODS: Expression of KAI1 and p53 was immunohistochemically determined in 75 biopsy specimens from patients with primary irradiated, invasive squamous cell cervical cancer and 30 cases with CIN I-III. RESULTS: In invasive cancer, 22 cases showed strong expression, 42 cases down-regulation, and 11 cases no expression of KAI1. All specimens with CIN I showed strong KAI1 expression, while in CIN II and III down-regulation was observed in 45% of cases. There was no significant correlation of KAI1 expression with clinical and histopathological parameters. No influence of KAI1 expression on prognosis was observed. CONCLUSIONS: KAI1-down-regulation is a frequent event in cervical cancer occurring early in carcinogenesis. KAI1 expression did not influence the prognosis of patients with primary irradiated cervical cancer. PMID- 11205304 TI - Detection of DNA-strand breaks in cells treated with F 11782, a catalytic inhibitor of topoisomerases I and II. AB - F 11782, or 2", 3"-bis pentafluorophenoxyacetyl-4',6'-ethylidene-beta-D glucoside of 4'-phosphate-4'-dimethylepipodophyllotoxin 2N-methyl glucamine salt, is a novel fluorinated lipophylic epipodophylloid which has proven cytotoxic activity in vitro and has shown markedly superior antitumour activity in vivo compared to etoposide in various experimental tumour models. However, the precise mechanism(s) of cytotoxicity of F 11782 remains to be defined. In this study, the DNA damaging activity of F 11782 was investigated in GCT27 and C6S cells using, respectively the fluorescence enhancement assay and the technique of DNA alkaline elution. All the results obtained were consistent with induction of DNA damage by F 11782. No evidence of any stabilisation of DNA-topoisomerase cleavable complexes though was obtained with this catalytic inhibitor. Furthermore, such induction of DNA damage has not been reported with other known catalytic topoisomerase inhibitors and so it appears to be unique to F 11782. PMID- 11205305 TI - Cytostatic, cytotoxic and protein tyrosine kinase inhibitory activity of ursolic acid in A431 human tumor cells. AB - The effect of the tritepene, ursolic acid, on the proliferation of A431 human epidermoid carcinoma cells was studied. According to our investigations, ursolic acid is a potent inhibitor of A431 cell growth. Ursolic acid markedly reduced A431 cell growth in a time- and dose-dependent manner. We found a good correlation between the results of direct cell counting and the MTT test. During long periods of drug exposure, ursolic acid exhibited both cytotoxic and cytostatic activity. The effect was partially reversible on drug removal. The greatest cytotoxicity was observed both in the trypan blue test and in the MTT test at 50 mM. Investigations on tyrosine kinase inhibition were performed by biochemical and cellular assays on A431 cells. Ursolic acid inhibited tyrosine kinase activity of A431 cells in biochemical assay in a dose-dependent manner with an IC50 of 24 mM. In cellular assay, when A431 cells were pretreated with ursolic acid for 24, 48 and 168 hours at various concentrations (5, 10, 20, 30 and 50 mM), lower values of IC50 were measured: 6.8 microM for 24 hours, 5.2 mM for 48 hours and 1.4 mM for 168 hours. The results suggest that ursolic acid exerts an antiproliferative effect through the inhibition of tyrosine kinase enzymes. PMID- 11205306 TI - Prognostic value of E-cadherin, beta-catenin, P120ctn in patients with transitional cell bladder cancer. AB - BACKGROUND: Loss of E-cadherin-catenin mediated adhesion is known to play a major role in tumour progression in many human carcinomas. MATERIALS AND METHODS: By means of immunohistochemistry, we have investigated the expression of E-cadherin, beta-catenin and p120ctn in 102 transitional cell bladder carcinomas (TCCs) and statistically analysed these expressions with known clinicopathological parameters and patient survival. RESULTS: Abnormal expression of E-cadherin, beta catenin and p120ctn was associated with high grade and high stage of TCCs (p < 0.001). Abnormal beta-catenin expression demonstrated a statistically significant correlation with poor patient survival (p = 0.03) while abnormal E-cadherin expression was associated with poor survival in patients with muscle invasive TCCs (p = 0.025). However, in multivariate statistical analysis a suggestive association with poor survival was observed only for E-cadherin (p = 0.06). Simultaneous abnormal expression of all the molecules demonstrated an association of suggestive significance with poor patient survival (p = 0.07). CONCLUSION: E cadherin expression may be a useful prognostic marker in patients with invasive TCCs. PMID- 11205307 TI - Heat shock protein-90, IL-6 and IL-10 in bladder cancer. AB - The progression of transitional-cell carcinomas of the bladder is associated with changes in general and local immune status. To understand the factors involved in the progression of transitional cell carcinoma and in the maintenance of an efficient anti-tumoural response, in this study we investigated by immunohistochemistry expression of HSP-90, IL-6 and IL-10 proteins in 56 surgical specimens obtained from superficial and deeply invasive bladder carcinomas. Of the 56 bladder carcinoma 52 (92.9%) expressed HSP-90, 48 (85.7%) IL-6 and 45 (80.3%) IL-10. High-grade and muscle-invasive tumours contained significantly higher levels of HSP-90 and IL-6 antibodies than low-grade and superficial tumours (p < 0.05). Linear regression showed a significant correlation between HSP-90 and IL-10 (p = 0.022) but not between HSP-90 and IL-6, or IL-6 and IL-10 expression. The variable quantities of HSP-90, IL-6 and IL-10 in the high-grade bladder carcinomas studied suggest that these proteins have independent functional roles and may be the immunogenic targets for an anti-tumoural response. PMID- 11205308 TI - The effects of gossypol on the invasiveness of MAT-LyLu cells and MAT-LyLu cells from the metastasized lungs of MAT-LyLu-bearing Copenhagen rats. AB - Recently, we isolated a novel subline of the MAT-LyLu cell line from the metastasized lungs of MAT-LyLu-bearing Copenhagen rats (MLL cells). In this study, we compared the MLL cells to the parental MAT-LyLu cells with respect to invasive ability, mRNA expression level for the nm23 metastasis suppressor gene, and response to gossypol (GP), a natural compound with documented antiproliferative and antimetastatic activity, in an in vitro invasion assay. ML cells were isolated from mechanically dissociated metastasized lungs from MAT LuLu-bearing Copenhagen rats. Comparisons of the invasive ability and steady state levels of nm23 mRNA between MLL and MAT-LuLu cells were determined by in vitro invasion assay and RT-PCR, respectively. The results show that MLL cells display a higher penetration percentage than MAT-LyLu cells in the in vitro invasion assay. Furthermore, RT-PCR revealed that MLL cells possess lower steady state levels of nm23 mRNA than MAT-LyLu cells, suggesting a molecular basis for the observed differences in in vitro invasive ability. Finally, both MLL and MAT LyLu cells were susceptible to gossypol, which induced dose-dependent inhibition of invasive activity. These results report the isolation of a novel, more highly invasive subline of the MAT-LyLu cell line that is as susceptible to the inhibitory effects of gossypol as the parental MAT-LyLu cells. The MLL cells, in combination with the parental MAT-LyLu cells, can be valuable tools for investigating the biology and behavior of metastatic cells and their response to chemotherapeutic/preventive agents. PMID- 11205309 TI - Different transendothelial migration behaviour pattern of blood monocytes derived from patients with benign and malignant diseases of the breast. AB - BACKGROUND: In this study we compared the expression of selected monocyte surface antigens with the potential to transmigrate through an endothelial layer before and after surgery from breast cancer patients (CA) and patients with benign disease of the breast (BE). MATERIALS AND METHODS: Transmigration capacity of mononuclear cells was determined after isolation by Ficoll density gradient, layered over human umbilical vein endothelial cells and cultured in a two chamber plate added with fMLP as a chemotactic stimulus. We determined monocyte phenotye (HLA-DR, FcgRI/CD64, CR1/CD11b and LFA-1/CD11a) and the phagocytosis of E. coli by flow cytometry. RESULTS: Before surgery blood monocytes had an equal expression of the measured surface antigens, but were different in regard to their interaction with endothelial cells. Monocytes derived from CA had a higher transmigration potency than those of BE. Moreover, the migration through the endothelial cell layer created different populations of monocytes. Surgical stress modified transmigrated monocytes of BE into the direction of monocytes from CA. Phagocytic capacity of peripheral blood monocytes from CA was significantly diminished and was further reduced after surgery when measured in transmigrated cells. CONCLUSION: Our study shows that monocytes from CA and BE can be discriminated in regard to their interaction with endothelial cells. PMID- 11205310 TI - Physiological mechanisms of radiation sensitization by pentoxifylline. AB - The aim of this study was to investigate whether multiple injections (daily for 5 days) of the hemorheological agent pentoxifylline (PTX) affected tumor physiological parameters (i.e., tumor pO2, tumor pH, and tumor interstitial fluid pressure) during the tumor growth of FSaII murine fibrosarcoma in C3H mice. The radiation sensitization by multiple injections of PTX (daily for 5 days) was also studied. Following multiple administrations of PTX, PTX significantly improved tumor oxygenation in all sizes of tumors tested. Our results showed that the elevated tumor interstitial fluid pressure (TIFP) in solid tumors could be reduced by PTX. Based on our results with the improvement in tumor pathophysiology, PTX may be of use during tumor therapies in which the outcome may be detrimentally affected by the presence of hypoxia. As anticipated, multiple injections of PTX with fractionated x-irradiation prolonged the radiation-induced growth delay in FSaII tumors, producing an enhancement ratio of 1.8 of the growth delay at 15 days. However, we did not observe any alteration in cellular oxygen consumption (QO2) after the treatment with PTX. Therefore, we concluded that PTX-induced radiosensitization was due to an increase in tumor pO2, not a reduction in QO2. PMID- 11205311 TI - Tempicol-3, a novel piperidine-N-oxide stable radical and antioxidant, with low toxicity acts as apoptosis inducer and cell proliferation modifier of Yoshida Sarcoma cells in vivo. AB - The novel nitroxyl, Tempicol-3 (nitroxide-N-oxide) was synthesized and its capacity to act as a scavenger of hydroxyl radicals was tested. The concentration dependent reducibility of this novel compound was also examined and compared with those of previously characterized nitroxides, Tempo and Tempace. The cytotoxicity of Tempicol-3 in vitro was measured by the modified tetrazolium assay (MTT), using, model cells for neoplastic phenotype (mouse NIH 3T3 fibroblast line). The ability of Tempicol-3 to act as an antitumor agent in vivo was also investigated in a pharmacological test, using rats bearing 3-day old Yoshida Sarcoma (promotion phase of the disease). Our results clearly indicated that Tempicol-3 acts as an effective and promising hydroxyl radical scavenger-antioxidant. Structure- and concentration-dependent bioreduction of Tempicol-3 by ascorbic acid may account for some of its biological effects, causing modulation of the antioxidant status of cells. The presence of one nitrone moiety per molecule of Tempicol-3 caused a significant decrease in nitroxide cytotoxicity as compared with Tempo, in vitro. The results clearly confirmed that the toxic effect could result either from the presence or structure of substituent(s) at position 4 of the free radical piperidine moiety. It can be stated that Tempicol-3 is a lowtoxicity nitroxide, which could be effective in providing antioxidative activity. We have also observed that lowtoxic Tempicol-3, at m.e.d. (minimal effective dose) suppressed tumorigenesis, acting as a cell proliferation modifier and apoptosis inducer in vivo. This work provides the base for further investigations on nitroxide-N-oxide derivatives since the serious question remains to be solved as to what is the molecular mechanism of action of the nitroxide-N-oxides. PMID- 11205312 TI - Immunohistochemical expression of the p53, p21/Waf-1, Rb, p16 and Ki67 proteins in multiple myeloma. AB - The aim of this study was to investigate the immunohistochemical expression of the proteins p53, Waf-l/p21, Rb, p16 and Ki67 in 38 cases of multiple myelomas (MM) and 4 cases of solitary extramedullary plasmacytomas in relation to the tumor histological grade and stage. In bone marrow (BM) biopsies from MM, overexpression of p53 and p21 proteins, in comparison to plasma cell infiltrates in non-pathological bone marrow, was detected in 13 out of 38 and 21 out of 38 cases, respectively. The combined immunoexpression of p53 and p21 proteins in the 38 cases of MM showed the following patterns: a) p53+/p21+ (13 cases) b) p53 /p21+ (8 cases) and c) p53-/p21- (17 cases). Rb, p16 and Ki67 proteins were detected in tumor cells in all 38 cases and their expression increased proportionally to tumor grade. The 4 cases of solitary extramedullary plasmacytomas showed the p53+/p21+ pattern in 2 cases and the p53-/p21+ pattern in 2 cases, all of them displaying Rb, p16 and Ki67 expression in tumor cells. The pattern p53+/p21+ might represent cases with wild-type p53 able to induce p21 expression. However, in previous studies p53 mutations were reported in about 3 10% of MM, and they were strongly associated with advanced disease. Thus, in some p53+/p21+ cases associated with high p53 expression and advanced disease, p53 gene cannot be excluded and up-regulation of p21 expression may be p53- independent. P53 overexpression correlated with increased tumor grade (p < 0.005), advanced histological stage (p < 0.001) and Ki67 expression in more than 10% of tumor cells (p < 0.001). Since increase in Ki67 expression also correlated with increased tumor grade (p < 0.001) and advanced histological stage (p < 0.001), these findings suggest that impairment of the p53 growth control pathway is associated with tumor progression in MM. Thus, p53 and Ki67 immunostaining in routine BM biopsies may be helpful for the detection of MM with potentially aggressive behavior. Overexpression of p21 in MM correlated with higher Ki67 expression (p < 0.005), suggesting that the p21 function of arresting cell-cycle is impaired. Ki-67 expression in MM increased in parallel with p16 (p < 0.001) and Rb expression (p < 0.001). Rb expression could represent a growth control response which, however, might not be able to induce growth arrest in view of the parallel increase in Ki67 expression and of previous findings showing that Rb protein in MM cells is expressed mostly in its phosphorylated form. PMID- 11205313 TI - PSC 833 induces apoptosis in drug-sensitive human leukemia cell line and modulates resistance to paclitaxel in its multidrug-resistant variant. AB - BACKGROUND: The non-immunosuppressive cyclosporine analog PSC 833 has been shown to reverse multidrug-resistance of neoplastic cells including the MDR-1 gene coded P-glycoprotein (P-gp)-mediated cells resistant to paclitaxel. MATERIALS AND METHODS: Apoptosis was demonstrated in drug-sensitive HL-60 and multidrug resistant human promyelocytic leukemia HL-60/ADR (MRP) and HL-60/VCR (MDR-1) cells in vitro with the aid of flow cytometry, DNA analysis and western blotting. RESULTS: The techniques used herein determined accumulation of paclitaxel/PSC 833 induced apoptotic cells with sub-G0 (hypodiploid) DNA content and blocked in the G2/M phase of the cell cycle, internucleosomal DNA fragmentation, poly (ADP ribose) polymerase cleavage, Bcl-2 modulation and Bax up-regulation, without any significant alterations in the levels of Bcl-xL, CD95/Fas or Fas-L proteins. CONCLUSION: Drug resistance modulator PSC 833 abolished the P-gp-mediated multidrug-resistance to paclitaxel and paclitaxel-induced apoptosis in human myeloid leukemia (HL-60/VCR) cells in vitro. Furthermore, PSC 833 alone induced apoptosis in parental drug-sensitive leukemia cells, but not in both multidrug resistant sublines studied. PMID- 11205314 TI - Suicide gene therapy of ovarian cancer: an experimental study in rats using retroviral-mediated transfer of herpes simplex virus thymidine kinase gene. AB - BACKGROUND: This study evaluated the potential of gene therapy against ovarian cancer usin the retroviral transfer of the herpes simplex type 1 thymidine kinase gene (HSV1-TK) followed by ganciclovir treatment. MATERIALS AND METHODS: The sensitivity of 4 different ovarian cancer cell lines (rat ar human) to in vitro infection by recombinant retroviruses were evaluated. Then, their HSV1-TK expressing derivatives were tested for their sensitivity to ganciclovir. One of them, DMBA-OC-1-TK+ was used to generate experimental ovarian cancer in 13 WKY female rats. After 14 days, tl rats received ganciclovir for 12 days (n = 6). The results were expressed in mean +/- ES and were evaluated with the Mann-Whitney test. RESULTS: All cell lines analyzed in this study were sensitive to retroviral mediated gene transfer although with significant variations. The HSV 1-TK expressing derivatives of these cells were 300 7,000-fold more sensitive to ganciclovir, than the parental cells. The ganciclovir dramatically reduced the size of HSV1-TK+ tumors compared to untreated control rats (0 mm3 vs 2,594 mm3, p < 0.001) with complete tumor regression and residual fibrotic scars on pathological examination. Control tumors showed a poorly-differentiated epithelial adenocarcinoma of the ovary. CONCLUSION: In a clinical perspective, the good tolerance and the significant anti-tumoral effects of retroviral mediated transfer of HSV1-TK gene in animals were encouraging. It remains to set up gene transfer methods that will allow efficient targeting of the ovarian cancer in vivo. PMID- 11205315 TI - Stability, toxicity and cytotoxicity of a cupric complex towards cultured CaCo-2 cells. AB - The human colon adenocarcinoma-derived cell line CaCo-2 was used as a model system to study the effects of copper (II), tetradentate N-alkyl ligand (H2L) and their complex. The stimulatory effect of the complex was obtained with lower concentrations from 10(-7) to 10(-17) mol.L-1, while inhibiting effects occur from 10(-4) to 10(-6) mol.L-1. According to this study, copper (II) and free ligand were toxic for cultured cells. Our data suggested that the complex, according to our toxicity assays in mice, could be used as an antimitotic agent. PMID- 11205316 TI - Synergistic effect of the angiogenesis inhibitor TNP-470 and tumor necrosis factor (TNF) on Bomirski Ab melanoma in hamsters. AB - Bomirski Ab transplantable melanoma bearing hamsters were treated with angiogenesis inhibitor TNP-470 or with rat tumor necrosis factor (TNF) at doses of 20 micrograms and 40 micrograms or with both TNP-470 and TNF at a dose of 20 micrograms each. The size of the growing tumor was measured everyday from the day when it was palpable. After the death of the animals the final size of their tumors was measured and the number and localisation of metastasis were determined. It was found that the rate of tumor growth was lowest in the group of animals treated with TNF at a dose of 40 micrograms and in the group of animals treated with TNP-470 and TNF at a dose of 20 micrograms. The frequency of metastasis was different in the experimental groups although their location was similar. The longest living animals belonged to the group treated with both TNP 470 and TNF. The results of the investigation indicate that TNP-470 and TNF act in a synergistic way that allows a decrease in the effective dose of TNF thus diminishing its noxious side effects. PMID- 11205317 TI - Technique and feasibility of a dual staining method for estrogen receptors and AgNORs. AB - A new staining method for dual demonstration of Estrogen receptors (ER) and argyrophilc Nucleolus-Organizer Regions (AgNORs) was developed. To rule out possible reciprocal effects, serial slides of 10 invasive ductale breast cancers were stained with either the single staining method or the simultaneous ER/AgNOR staining method and investigated comparatively. By measuring the slides with the image analysis system AMBA, reciprocal effects could be excluded. It was proven that dual staining of both markers results in a reproducible and specific staining result. We concluded that it is justified to measure AgNORs in immunohistochemically stained cells. PMID- 11205318 TI - Different proliferation patterns in breast cancer: AgNOR measurements in ER negative and ER-positive tumor cells. AB - The relation between estrogen receptors (ER) and argyrophilic nucleolar organizer regions (AgNORs) in situ within human breast cancer cells was analyzed. For AgNOR measurements in 49 invasive breast carcinomas, a new reproducible staining method for dual demonstration of ER and AgNORs was applied. Quantitative AgNOR variables were determined in ER-positive and ER-negative tumor cells by digital image analysis. The relationships between AgNOR parameters of ER-positive and ER negative cells and other prognostic factors of breast cancer [Bloom-Richardson Grading and growth fraction (Ki-67 index)] were investigated. A higher AgNOR content in ER-negative cells and a special clustering phenomenon in ER-positive tumor cells were found. Correlation with other criteria of malignant potential could be exclusively demonstrated for ER-negative cells. ER-negative cells of breast cancer can be characterized as the more malignant and possibly prognosis dictating cell fraction. Thus, ER-negative cells probably contribute more to the progression of the tumor disease and furthermore to the prognosis than ER positive cells. We recommend measurement AgNORs exclusively in ER-negative cells of breast cancer. PMID- 11205319 TI - Restriction enzyme analysis of DNA methylation in "condensed" chromatin of Ha-ras transformed NIH 3T3 cells. AB - Increased amounts of chromatin condensation (i.e., localized areas of high DNA density, or chromatin higher order packing state) have been described in NIH 3T3 cells transformed with the Ha-ras oncogene. The structural basis for this oncogene-mediated alteration in nuclear organization is unknown. Since DNA methylation is likely to be involved in regulating the nucleosomal level of DNA packaging, we studied the role of DNA methylation in higher-order chromatin organization induced by Ha-ras. CpG-methylated DNA content was estimated in "condensed" chromatin of Ha-ras-transformed NIH 3T3 cell lines which differ in ras expression and ras-induced metastatic ability but present approximately the same values of "condensed" chromatin areas. The question posed was that if DNA methylation were involved with the chromatin higher-order organization induced by Ha-ras in these cell lines, the methylated DNA density in the "condensed" chromatin would also be the same. The DNA evaluation was performed by video image analysis in Feulgen-stained cells previously subjected to treatment with Msp I and Hpa II restriction enzymes, which distinguish between methylated and non methylated DNA. The amount of methylated CpG sequences not digested by Hpa II in "condensed" chromatin regions was found to vary in the studied ras-transformed cell lines. DNA CpG methylation status is thus suggested not to be involved with the higher order chromatin condensation induced by ras transformation in the mentioned NIH 3T3 cell lines. PMID- 11205320 TI - Topography of genetic loci in tissue samples: towards new diagnostic tool using interphase FISH and high-resolution image analysis techniques. AB - Using single and dual colour fluorescence in situ hybridisation (FISH) combined with image analysis techniques the topographic characteristics of genes and centromeres in nuclei of human colon tissue cells were investigated. The distributions of distances from the centre-of-nucleus to genes (centromeres) and from genes to genes (centromeres to centromeres) were studied in normal colon tissue cells found in the neighbourhood of tumour samples, in tumour cell line HT 29 and in promyelocytic HL-60 cell line for comparison. Our results show that the topography of genetic loci determined in 3D-fixed cell tissue corresponds to that obtained for 2D-fixed cells separated from the tissue. The distributions of the centre-of-nucleus to gene (centromere) distances and gene to gene (centromere to centromere) distances and their average values are different for various genetic loci but similar for normal colon tissue cells, HT-29 colon tumour cell line and HL-60 promyelocytic cell line. It suggests that the arrangement of genetic loci in cell nucleus is conserved in different types of human cells. The investigations of trisomic loci in HT-29 cells revealed that the location of the third genetic element is not different from the location of two homologues in diploid cells. We have shown that the topographic parameters used in our experiments for different genetic elements are not tissue or tumour specific. In order to validate high-resolution cytometry for oncology, further investigations should include more precise parameters reflecting the state of chromatin in the neighbourhood of critical oncogenes or tumour suppresser genes. PMID- 11205321 TI - Malignancy-associated changes in breast tissue detected by image cytometry. AB - In several tissues, nuclear differences have been described in normal-appearing cells from patients with invasive carcinomas compared to cases without invasive carcinoma, a phenomenon known as malignancy-associated changes (MACs). The aim of this study was to determine the presence of malignancy-associated changes in breast tissue. Image cytometry was performed on Feulgen stained tissue sections of patients with usual ductal hyperplasia with (n = 30) or without (n = 41) adjacent invasive breast carcinoma. Nuclear features of normal-appearing cells as well as of usual ductal hyperplastic cells were separately compared between the two groups. Many features of normal-appearing epithelial cells were significantly different between cases with and without invasive cancer. Significant differences were also found by measuring ductal hyperplastic nuclei instead of normal appearing nuclei. Cases with or without cancer could be distinguished with a classification accuracy of 80% by discriminant analysis using 2 nuclear features derived from ductal hyperplastic cells. In conclusion, image cytometry on breast tissue sections shows that malignancy-associated changes can be found in normal as well as in usual ductal hyperplastic breast cells. This could be clinically relevant for the detection of occult breast cancer, for the prediction of risk in these lesions, and to monitor the effect of chemopreventive agents. PMID- 11205322 TI - Chromosomal composition of aneuploid clones with different DNA contents in head and neck squamous cell carcinomas as determined by combined flow cytometry and fluorescence in situ hybridization. AB - Studies with DNA flow cytometry (FCM) have shown that DNA contents of aneuploid tumour clones vary in a wide range. The aim of this study was to analyse whether homologous chromosomal changes exist despite the individual differences that may be of general relevance for the development of gross aneuploidy in squamous cell carcinomas of the head and neck. Fluorescence in situ hybridization (FISH) with 13 centromere-specific DNA probes was applied to 3 diploid and 11 aneuploid tumours with DNA indices ranging between 0.8 and 2.2. Disomic and monosomic cell populations were prevalent findings in DNA-diploid tumours. Polysomies were common in aneuploid tumours. Different degrees of aneusomy for identical chromosomes were recurrent features in aneuploid tumours. FISH signal heterogeneity was identified for all chromosomes. The mean number of aneusomic cell populations identified for DNA-aneuploid tumours ranged between 1.6 for chromosome 17 and 3.1 for chromosome 3. Inconsistencies between FISH and FCM data may indicate that centromere-specific DNA probes identify gains and losses of marker DNA due to complex karyotypic rearrangements rather than absolute changes in chromosome numbers. Overall, there was no evidence of the critical involvement of particular chromosomes in the development of different DNA contents. PMID- 11205323 TI - Reverse genetic studies of homologous DNA recombination using the chicken B lymphocyte line, DT40. AB - DT40 is an avian leucosis virus-transformed chicken B-lymphocyte line which exhibits high ratios of targeted to random integration of transfected DNA constructs. This efficient targeted integration may be related to the ongoing diversification of the variable segment of the immunoglobulin gene through homologous DNA recombination-controlled gene conversion. DT40s are a convenient model system for making gene-targeted mutants. Another advantage is the relative tractability of these cells, which makes it possible to disrupt multiple genes in a single cell and to generate conditionally gene-targeted mutants including temperature-sensitive mutants. There are strong phenotypic similarities between murine and DT40 mutants of various genes involved in DNA recombination. These similarities confirm that the DT40 cell line is a reasonable model for the analysis of vertebrate DNA recombination, despite obvious concerns associated with the use of a transformed cell line, which may have certain cell-line specific characteristics. Here we describe our studies of homologous DNA recombination in vertebrate somatic cells using reverse genetics in DT40 cells. PMID- 11205324 TI - Indirect and direct evidence for DNA double-strand breaks in hypermutating immunoglobulin genes. AB - The generation of a diverse antigen receptor repertoire is fundamental for the functionality of the adaptive immune system. While the V(D)J recombination process that generates the primary antigen receptor repertoire is understood in great detail, it is still unclear by which mechanism immunoglobulin (Ig) genes are further diversified by somatic hypermutation. Using mouse strains that carry a non-functional, pre-defined V(H)D(H)J(H) gene segment in their IgH locus we demonstrate DNA double-strand breaks (DSBs) in and around V(H)D(H)J(H) in B cells undergoing somatic hypermutation. The generation of these DSBs depends on transcriptional activity, and their distribution along the V(H)D(H)J(H) segment parallels that of point mutations in the hypermutation domain. Furthermore, similar to hot spots of somatic hypermutation, 50-60% of all DSBs occur preferentially at RGYW motifs. DSBs may transiently dissociate the Ig promoter from the intronic enhancer to block further transcription and to initiate an error-prone non-homologous DSB repair pathway. In accord with this model large deletions are frequently produced, along with point mutations, in a V(H)D(H)J(H) segment inserted together with its promoter into the IgH locus in inverted orientation. Our data suggest that DSBs are reaction intermediates of the mechanism underlying somatic hypermutation. PMID- 11205325 TI - Somatic hypermutation of immunoglobulin and non-immunoglobulin genes. AB - Somatic hypermutation (SHM) of immunoglobulin (Ig) genes is a highly specific mechanism restricted to B lymphocytes during only a few cell generations. Data presented here suggest that transcription of the target genes is required, but not sufficient for SHM. Presumably, cis-acting elements, such as those present in the Ig enhancers, are required to target a mutator factor (MuF) to Ig and human BCL-6 genes. It is postulated that the MuF travels with the transcribing RNA polymerase and is deposited on the target gene when the polymerase pauses. Point mutations, and rare deletions and insertions, are created by the combined actions of MuF and certain DNA polymerases. A subset of the mutations is corrected during SHM by DNA mismatch repair. PMID- 11205326 TI - In vivo and in vitro studies of immunoglobulin gene somatic hypermutation. AB - Following antigen encounter, two distinct processes modify immunoglobulin genes. The variable region is diversified by somatic hypermutation while the constant region may be changed by class-switch recombination. Although both genetic events can occur concurrently within germinal centre B cells, there are examples of each occurring independently of the other. Here we compare the contributions of class switch recombination and somatic hypermutation to the diversification of the serum immunoglobulin repertoire and review evidence that suggests that, despite clear differences, the two processes may share some aspects of their mechanism in common. PMID- 11205328 TI - Mutagenesis in eukaryotes dependent on DNA polymerase zeta and Rev1p. AB - DNA polymerase zeta (Pol zeta) and Rev1p carry out translesion replication in budding yeast, Saccharomyces cerevisiae, and are jointly responsible for almost all base pair substitution and frameshift mutations induced by DNA damage in this organism. In addition, Pol zeta is responsible for the majority of spontaneous mutations in yeast and has been proposed as the enzyme responsible for somatic hypermutability. Pol zeta, a non-processive enzyme that lacks a 3' to 5' exonuclease proofreading activity, is composed of Rev3p, the catalytic subunit, and a second subunit encoded by REV7. In keeping with its role, extension by Pol zeta is relatively tolerant of abnormal DNA structure at the primer terminus and is much more capable of extension from terminal mismatches than yeast DNA polymerase alpha (Pol alpha). Rev1p is a bifunctional enzyme that possesses a deoxycytidyl transferase activity that incorporates deoxycytidyl opposite abasic sites in the template and a second, at present poorly defined, activity that is required for the bypass of a variety of lesions as well as abasic sites. Human homologues of the yeast REV1 and REV3 have been identified and, based on the phenotype of cells producing antisense RNA to one or other of these genes, their products appear also to be employed in translation replication and spontaneous mutagenesis. We suggest that Pol zeta is best regarded as a replication enzyme, albeit one that is used only intermittently, that promotes extension at forks the progress of which is blocked for any reason, whether the presence of an unedited terminal mismatch or unrepaired DNA lesion. PMID- 11205327 TI - Hypermutation in bacteria and other cellular systems. AB - A temporary state of hypermutation can in principle arise through an increase in the rate of polymerase errors (which may or may not be triggered by template damage) and/or through abrogation of fidelity mechanisms such as proofreading and mismatch correction. In bacteria there are numerous examples of transient mutator states, often occurring as a consequence of stress. They may be targeted to certain regions of the DNA, for example by transcription or by recombination. The initial errors are made by various DNA polymerases which vary in their error proneness: several are inducible and are under the control of the SOS system. There are several structurally related polymerases in mammals that have recently come to light and that have unusual properties, such as the ability to carry out 'accurate' translesion synthesis opposite sites of template damage or the possession of exceedingly high misincorporation rates. In bacteria the initial errors may be genuinely spontaneous polymerase errors or they may be triggered by damage to the template strand, for example as a result of attack by active oxidative species such as singlet oxygen. In mammalian cells, hypermutable states persisting for many generations have been shown to be induced by various agents, not all of them DNA damaging agents. A hypermutable state induced by ionizing radiation in male germ cells in the mouse results in a high rate of sequence errors in certain unstable minisatellite loci; the mechanism is unclear but believed to be associated with recombination events. PMID- 11205329 TI - A new class of errant DNA polymerases provides candidates for somatic hypermutation. AB - The mechanism of somatic hypermutation of the immunoglobulin genes remains a mystery after nearly 30 years of intensive research in the field. While many clues to the process have been discovered in terms of the genetic elements required in the immunoglobulin genes, the key enzymatic players that mediate the introduction of mutations into the variable region are unknown. The recent wave of newly discovered eukaryotic DNA polymerases have given a fresh supply of potential candidates and a renewed vigour in the search for the elusive mutator factor governing affinity maturation. In this paper, we discuss the relevant genetic and biochemical evidence known to date regarding both somatic hypermutation and the new DNA polymerases and address how the two fields can be brought together to identify the strongest candidates for further study. In particular we discuss evidence for the in vitro biochemical misincorporation properties of human Rad30B/Pol iota and how it compares to the in vivo somatic hypermutation spectra. PMID- 11205330 TI - Altered spectra of hypermutation in DNA repair-deficient mice. AB - Affinity maturation of the humoral immune response is based on the ability of immunoglobulin variable genes to undergo a process of rapid and extensive somatic mutation followed by antigenic selection for antibodies with higher affinity. While the behaviour of this somatic hypermutation phenomenon has been well characterized over the last 20 years, the molecular mechanism responsible for inserting mutations has remained shrouded. To better understand this mechanism, we studied the interplay between hypermutation and other DNA associated activities such as DNA repair. There was no effect on the frequency and pattern of hypermutation in mice deficient for nucleotide excision repair, base excision repair and ataxia-telangiectasia mutated gene repair of double strand breaks. However, variable genes from mice lacking some components of mismatch repair had an increased frequency of tandem mutations and had more mutations of G and C nucleotides. These results suggest that the DNA polymerase(s) involved in the hypermutation pathway produces a unique spectra of mutations, which is then altered by mismatch repair and antigenic selection. We, also describe the differential pattern of expression of some nuclear DNA polymerases in hypermutating versus non-hypermutating B lymphocytes. The rapidly dividing germinal centre B cells expressed DNA polymerases alpha, beta, delta, epsilon and zeta, whereas the resting non-germinal centre cells did not express polymerases alpha or epsilon at detectable levels, although they did express polymerases beta, delta and zeta. The lack of expression of polymerase epsilon in the non germinal centre cells suggests that this enzyme has a critical role in chromosomal replication but does not participate in DNA repair in these cells. PMID- 11205331 TI - DNA polymerase iota and related rad30-like enzymes. AB - Until recently, the molecular mechanisms of translesion DNA synthesis (TLS), a process whereby a damaged base is used as a template for continued replication, was poorly understood. This area of scientific research has, however, been revolutionized by the finding that proteins long implicated in TLS are, in fact, DNA polymerases. Members of this so-called UmuC/DinB/Rev1/Rad30 superfamily of polymerases have been identified in prokaryotes, eukaryotes and archaea. Biochemical studies with the highly purified polymerases reveal that some, but not all, can traverse blocking lesions in template DNA. All of them share a common feature, however, in that they exhibit low fidelity when replicating undamaged DNA. Of particular interest to us is the Rad30 subfamily of polymerases found exclusively in eukaryotes. Humans possess two Rad30 paralogs, Rad30A and Rad30B. The RAD30A gene encodes DNA polymerase eta and defects in the protein lead to the xeroderma pigmentosum variant (XP-V) phenotype in humans. Very recently RAD30B has also been shown to encode a novel DNA polymerase, designated as Pol iota. Based upon in vitro studies, it appears that Pol iota has the lowest fidelity of any eukaryotic polymerase studied to date and we speculate as to the possible cellular functions of such a remarkably error-prone DNA polymerase. PMID- 11205332 TI - The reverse transcriptase model of somatic hypermutation. AB - The evidence supporting the reverse transcriptase model of somatic hypermutation is critically reviewed. The model provides a coherent explanation for many apparently unrelated findings. We also show that the somatic hypermutation pattern in the human BCL-6 gene can be interpreted in terms of the reverse transcriptase model and the notion of feedback of somatically mutated sequences to the germline over evolutionary time. PMID- 11205333 TI - Evolution and the molecular basis of somatic hypermutation of antigen receptor genes. AB - Somatic hypermutation of immunoglobulin genes occurs in many vertebrates including sharks, frogs, camels, humans and mice. Similarities among species reveal a common mechanism and these include the AGC/T sequence hot spot, preponderance of base substitutions, a bias towards transitions and strand bias. There are some differences among species, however, that may unveil layers of the mechanism. These include a G:C bias in frog and shark IgM but not in nurse shark antigen receptor (NAR), a high frequency of doublets in NAR hypermutation, and the co-occurrence of somatic hypermutation with gene conversion in some species. Here we argue that some of the similarities and differences among species are best explained by error-prone DNA synthesis by the translesion synthesis DNA polymerase zeta (Pol zeta) and, as suggested by others, induction of DNA synthesis by DNA breaks in antigen receptor variable genes. Finally, targeting of the variable genes is probably obtained via transcription-related elements, and it is the targeting phase of somatic hypermutation that is the most likely to reveal molecules unique to adaptive immunity. PMID- 11205335 TI - Molecular definition of the germinal centre stage of B-cell differentiation. AB - Genomic-scale gene expression analysis provides views of biological processes as a whole that are difficult to obtain using traditional single-gene experimental approaches. In the case of differentiating systems, gene expression profiting can define a stage of differentiation by the characteristic expression of hundreds of genes. Using specialized DNA microarrays termed 'Lymphochips', gene expression during mature B-cell differentiation has been defined. Germinal centre B cells represent a stage of differentiation that can be defined by a gene expression signature that is not shared by other highly proliferative B-cell populations such as mitogenically activated peripheral blood B cells. The germinal centre gene expression signature is maintained to a significant degree in lymphoma cell lines derived from this stage of differentiation, demonstrating that this gene expression programme does not require ongoing interactions with other germinal centre cell types. Analysis of representative cDNA libraries prepared from resting and activated peripheral blood B cells, germinal centre centroblasts, centrocytes and tonsillar memory B cells has confirmed and extended the results of DNA microarray gene expression analysis. PMID- 11205336 TI - Transcription, beta-like DNA polymerases and hypermutation. AB - This paper discusses two aspects of immunoglobulin (Ig) gene hypermutation. In the first approach, a transcription termination signal is introduced in an Ig light chain transgene acting as a mutation substrate, and transgenic lines are generated with control and mutant transgenes integrated in tandem. Analysis of transcription levels and mutation frequencies between mutant and control transgenes clearly dissociates transcription elongation and mutation, and therefore argues against models whereby specific pausing of the RNA polymerase during V gene transcription would trigger an error-prone repair process. The second part reports the identification of two novel beta-like DNA polymerases named Pol lambda and Pol mu, one of which (Pol mu) represents a good candidate for the Ig mutase due to its higher lymphoid expression and its similarity with the lymphoid enzyme terminal deoxynucleotidyl transferase. Peculiar features of the expression of this gene, including an unusual splicing variability and a splicing inhibition in response to DNA-damaging agents, are discussed. PMID- 11205334 TI - Somatic hypermutation and B-cell lymphoma. AB - During the B-cell response to T-cell-dependent antigens, the B cells undergo a rapid proliferative phase in the germinal centre. This is accompanied by the introduction of mutations into the immunoglobulin (Ig) variable region (V) genes. The B cells are then selected according to the affinity of the encoded immunoglobulin for antigen, resulting in affinity maturation of the response. Analysis of mutations in IgV genes has given insight into the history of individual B cells and their malignancies. In most cases, analysis of mutations confirms classifications of B-cell lineage designated by studies of cellular morphology and surface antigen expression. However, of particular interest is the subdivision of groups of malignancies by analysis of somatic hypermutation. It is now apparent that there are two subsets of chronic lymphocytic leukaemia (CLL), one with a low load of mutations and poor prognosis. and one with a heavy load of mutations with a much more favourable prognosis. In addition, in Burkitt's lymphoma, sporadic and endemic subtypes are now considered possibly to have a different pathogenesis, reflected in differences in the numbers of mutations. Hodgkin's disease, which was a mystery for many years, has now been shown to be a B-cell tumour. Although in many cases the Ig genes are crippled by somatic hypermutation, it is thought that failure to express Ig is more likely to be associated with problems of transcription. It has been proposed that the distribution of mutations in a B-cell lymphoma can be used to determine whether a lymphoma is selected. We have investigated the load and distribution of mutations in one group of lymphomas--marginal zone B-cell lymphomas of mucosa-associated lymphoid tissues (MALT-type lymphoma), which are dependent on Helicobacter pylori for disease progression, to investigate the limits of information that can be derived from such studies. Comparison of the load of mutations demonstrates that these tumours have approximately the same load of mutations as normal mucosal marginal zone B cells from the Peyer's patches and mucosal plasma cells. This is consistent with the origin of these cells from mucosal marginal zone B cells with plasma cell differentiation. To investigate selection in MALT lymphomas we compared a region of the framework region three in ten MALT lymphomas which use the V(H4) family, with the same codons in groups of V(H4) genes that are out of frame between V and J. The latter accumulate mutations but are not used and are not selected. A group of V(H4) genes are in-frame between V and J were also included for comparison. There were no obvious differences in the distribution of mutations between the groups of genes; the same hot spots and cold spots were apparent in each. In the MALT lymphomas, selection was apparent in the framework regions only and the tendency was to conserve. We therefore feel that there is selection to conserve antibody structure and that this does not reflect selection for antigen. We do not believe that antigen selection can be deduced reliably from sequence information alone. It is possible that somatic hypermutation could be a cause of malignancy since it has been shown that the process may generate DNA strand breaks and is known to be able to generate insertions and deletions. Such events may mediate the translocation of genes--a process that is pivotal in the evolution of many lymphomas. PMID- 11205337 TI - DNA polymerase mu, a candidate hypermutase? AB - A novel DNA polymerase (Pol mu) has been recently identified in human cells. The amino-acid sequence of Pol mu is 42% identical to that of terminal deoxynucleotidyl transferase (TdT), a DNA-independent DNA polymerase that contributes to antigen-receptor diversity. In this paper we review the evidence supporting the role of Pol mu in somatic hypermutation of immunoglobulin genes, a T-dependent process that selectively occurs at germinal centres: (i) preferential expression in secondary lymphoid organs; (ii) expression associated to developing germinal centres; and (iii) very low base discrimination during DNA-dependent DNA polymerization by Pol mu, a mutator phenotype enormously accentuated by the presence of activating Mn2+ ions. Moreover, its similarity to TdT, together with extrapolation to the crystal structure of DNA polymerase beta complexed (Pol beta) with DNA, allows us to discuss the structural basis for the unprecedented error proneness of Pol mu, and to predict that Pol mu is structurally well suited to participate also in DNA end-filling steps occurring both during V(D)J recombination and repair of DNA double-strand breaks that are processed by non homologous end-joining. PMID- 11205339 TI - Motor learning through the combination of primitives. AB - In this paper we discuss a new perspective on how the central nervous system (CNS) represents and solves some of the most fundamental computational problems of motor control. In particular, we consider the task of transforming a planned limb movement into an adequate set of motor commands. To carry out this task the CNS must solve a complex inverse dynamic problem. This problem involves the transformation from a desired motion to the forces that are needed to drive the limb. The inverse dynamic problem is a hard computational challenge because of the need to coordinate multiple limb segments and because of the continuous changes in the mechanical properties of the limbs and of the environment with which they come in contact. A number of studies of motor learning have provided support for the idea that the CNS creates, updates and exploits internal representations of limb dynamics in order to deal with the complexity of inverse dynamics. Here we discuss how such internal representations are likely to be built by combining the modular primitives in the spinal cord as well as other building blocks found in higher brain structures. Experimental studies on spinalized frogs and rats have led to the conclusion that the premotor circuits within the spinal cord are organized into a set of discrete modules. Each module, when activated, induces a specific force field and the simultaneous activation of multiple modules leads to the vectorial combination of the corresponding fields. We regard these force fields as computational primitives that are used by the CNS for generating a rich grammar of motor behaviours. PMID- 11205341 TI - Illustrating cerebral function: the iconography of arrows. AB - For over a century the arrow has appeared in illustrations of cerebral function, yet the implications of using such symbols have not been previously considered. This review seeks to outline the nature, evolution, applications and limitations of this deceptively simple graphic device when it is used to picture functions of the brain. The arrow is found to have been used in several different ways: as a means of endowing anatomical structures with functional properties; as a method of displaying neural function either in free-standing form or in a structural or spatial framework; as a device for correlating functional data with underlying brain topography; and as a technique for linking functions of the brain with the world outside and with various philosophical concepts. For many of these uses the essential feature of the arrow is its directional characteristic. In contrast to the line, it is direction that enables the arrow to display information about time, which in turn can be exploited to depict functional rather than structural data. However, the use of the arrow is fraught with difficulties. It is often unclear whether an arrow has been used to illustrate fact, hypothesis, impression or possibility, or merely to provide a decorative flourish. Furthermore, the powerful symbolic nature of the arrow can so easily confer a spurious validity on the conjectural. Increasingly now there are insuperable difficulties when attempting to illustrate complex mechanisms of brain function. In the iconography of cerebral function, therefore, arrows with all their ambiguities may in certain circumstances become superseded by more non-representational symbols such as the abstract devices of the computational neuroscientist. PMID- 11205338 TI - The functions of the proprioceptors of the eye muscles. AB - This article sets out to present a fairly comprehensive review of our knowledge about the functions of the receptors that have been found in the extraocular muscles--the six muscles that move each eye of vertebrates in its orbit--of all the animals in which they have been sought, including Man. Since their discovery at the beginning of the 20th century these receptors have, at various times, been credited with important roles in the control of eye movement and the construction of extrapersonal space and have also been denied any function whatsoever. Experiments intended to study the actions of eye muscle receptors and, even more so, opinions (and indeed polemic) derived from these observations have been influenced by the changing fashions and beliefs about the more general question of how limb position and movement is detected by the brain and which signals contribute to those aspects of this that are perceived (kinaesthesis). But the conclusions drawn from studies on the eye have also influenced beliefs about the mechanisms of kinaesthesis and, arguably, this influence has been even larger than that in the converse direction. Experimental evidence accumulated over rather more than a century is set out and discussed. It supports the view that, at the beginning of the 21st century, there are excellent grounds for believing that the receptors in the extraocular muscles are indeed proprioceptors, that is to say that the signals that they send into the brain are used to provide information about the position and movement of the eye in the orbit. It seems that this information is important in the control of eye movements of at least some types, and in the determination by the brain of the direction of gaze and the relationship of the organism to its environment. In addition, signals from these receptors in the eye muscles are seen to be necessary for the development of normal mechanisms of visual analysis in the mammalian visual cortex and for both the development and maintenance of normal visuomotor behaviour. Man is among those vertebrates to whose brains eye muscle proprioceptive signals provide information apparently used in normal sensorimotor functions; these include various aspects of perception, and of the control of eye movement. It is possible that abnormalities of the eye muscle proprioceptors and their signals may play a part in the genesis of some types of human squint (strabismus); conversely studies of patients with squint in the course of their surgical or pharmacological treatment have yielded much interesting evidence about the central actions of the proprioceptive signals from the extraocular muscles. The results of experiments on the eye have played a large part in the historical controversy, now in at least its third century, about the origin of signals that inform the brain about movement of parts of the body. Some of these results, and more of the interpretations of them, now need to be critically re-examined. The re-examination in the light of recent experiments that is presented here does not support many of the conclusions confidently drawn in the past and leads to both new insights and fresh questions about the roles of information from motor signals flowing out of the brain and that from signals from the peripheral receptors flowing into it. There remain many lacunae in our knowledge and filling some of these will, it is contended, be essential to advance our understanding further. It is argued that such understanding of eye muscle proprioception is a necessary part of the understanding of the physiology and pathophysiology of eye movement control and that it is also essential to an account of how organisms, including Man, build and maintain knowledge of their relationship to the external visual world. The eye would seem to provide a uniquely favourable system in which to study the way in which information derived within the brain about motor actions may interact with signals flowing in from peripheral receptors. The review is constructed in relatively independent sections that deal with particular topics. It ends with a fairly brief piece in which the author sets out some personal views about what has been achieved recently and what most immediately needs to be done. It also suggests some lines of study that appear to the author to be important for the future. PMID- 11205340 TI - Abnormalities in the awareness and control of action. AB - Much of the functioning of the motor system occurs without awareness. Nevertheless, we are aware of some aspects of the current state of the system and we can prepare and make movements in the imagination. These mental representations of the actual and possible states of the system are based on two sources: sensory signals from skin and muscles, and the stream of motor commands that have been issued to the system. Damage to the neural substrates of the motor system can lead to abnormalities in the awareness of action as well as defects in the control of action. We provide a framework for understanding how these various abnormalities of awareness can arise. Patients with phantom limbs or with anosognosia experience the illusion that they can move their limbs. We suggest that these representations of movement are based on streams of motor commands rather than sensory signals. Patients with utilization behaviour or with delusions of control can no longer properly link their intentions to their actions. In these cases the impairment lies in the representation of intended movements. The location of the neural damage associated with these disorders suggests that representations of the current and predicted state of the motor system are in parietal cortex, while representations of intended actions are found in prefrontal and premotor cortex. PMID- 11205343 TI - The Croonian Lecture 2000. Nicotinic acetylcholine receptor and the structural basis of fast synaptic transmission. AB - Communication in the nervous system takes place at chemical and electrical synapses, where neurotransmitter-gated ion channels, such as the nicotinic acetylcholine (ACh) receptor, and gap junction channels control propagation of electrical signals from one cell to the next. Newly developed electron crystallographic methods have revealed the structures of these channels trapped in open as well as closed states, suggesting how they work. The ACh receptor has large vestibules extending from the membrane which shape the ACh-binding pockets and facilitate selective transport of cations across a narrow membrane-spanning pore. When ACh enters the pockets it triggers a concerted conformational change that opens the pore by destabilizing a gate in the middle of the membrane made by a ring of pore-lining alpha-helical segmets. The alternative 'open' configuration of pore-lining segments reshapes the lumen and creates new surfaces, allowing the ions to pass through. The gap junction channel uses a similar structural mechanism, involving coordinated rearrangements of alpha-helical segments in the plane of the membrane, to open its pore. PMID- 11205344 TI - Causality in medicine: the case of tumours and viruses. AB - Clarification of the aetiology of chronic human diseases such as atherosclerosis or cancer is one of the dominant topics in contemporary medical research. It is believed that identification of the causal factors will enable more efficient prevention and diagnosis of these diseases and, in some instances, also permit more effective therapy. The task is difficult because of the multistep and multifactorial origin of these diseases. A special case in contemporary aetiological studies is definition of the role of viruses in the pathogenesis of human cancer. Virus-associated cancer develops only in a small minority of infected subjects, which implies that, if the virus does play a role in the pathogenesis of the malignancy, other factors must also be involved. In this paper the author attempts to review the present methodological approaches to aetiological studies of chronic diseases, discusses the role of criteria for identifying causal relationships and proposes guidelines that might help to determine the role of viruses in human cancer. PMID- 11205345 TI - The omnivorous Tyrolean Iceman: colon contents (meat, cereals, pollen, moss and whipworm) and stable isotope analyses. AB - The contents of the colon of the Tyrolean Iceman who lived ca. 5300 years ago include muscle fibres, cereal remains, a diversity of pollen, and most notably that of the hop hornbeam (Ostrya carpinifolia) retaining cellular contents, as well as a moss leaf (Neckera complanata) and eggs of the parasitic whipworm (Trichuris trichiura). Based almost solely on stable isotope analyses and ignoring the work on the colon contents, two recently published papers on the Iceman's diet draw ill-founded conclusions about vegetarianism and even veganism. Neither the pollen nor the moss is likely to have been deliberately consumed as food by the Iceman. All the available evidence concerning the Iceman's broad based diet is reviewed and the significance of the colon contents for matters other than assessment of food intake is outlined. PMID- 11205342 TI - Zonal organization of the mammalian main and accessory olfactory systems. AB - Zonal organization is one of the characteristic features observed in both main and accessory olfactory systems. In the main olfactory system, most of the odorant receptors are classified into four groups according to their zonal expression patterns in the olfactory epithelium. Each group of odorant receptors is expressed by sensory neurons distributed within one of four circumscribed zones. Olfactory sensory neurons in a given zone of the epithelium project their axons to the glomeruli in a corresponding zone of the main olfactory bulb. Glomeruli in the same zone tend to represent similar odorant receptors having similar tuning specificity to odorants. Vomeronasal receptors (or pheromone receptors) are classified into two groups in the accessory olfactory system. Each group of receptors is expressed by vomeronasal sensory neurons in either the apical or basal zone of the vomeronasal epithelium. Sensory neurons in the apical zone project their axons to the rostral zone of the accessory olfactory bulb and form synaptic connections with mitral tufted cells belonging to the rostral zone. Signals originated from basal zone sensory neurons are sent to mitral tufted cells in the caudal zone of the accessory olfactory bulb. We discuss functional implications of the zonal organization in both main and accessory olfactory systems. PMID- 11205346 TI - Effects of metapopulation processes on measures of genetic diversity. AB - Many species persist as a metapopulation under a balance between the local extinction of subpopulations or demes and their recolonization through dispersal from occupied patches. Here we review the growing body of literature dealing with the genetic consequences of such population turnover. We focus our attention principally on theoretical studies of a classical metapopulation with a 'finite island' model of population structure, rather than on 'continent-island' models or 'source-sink' models. In particular, we concern ourselves with the subset of geographically subdivided population models in which it is assumed that all demes are liable to extinction from time to time and that all demes receive immigrants. Early studies of the genetic effects of population turnover focused on population differentiation, such as measured by F(ST). A key advantage of F(ST) over absolute measures of diversity is its relative independence of the mutation process, so that different genes in the same species may be compared. Another advantage is that F(ST) will usually equilibrate more quickly following perturbations than will absolute levels of diversity. However, because F(ST) is a ratio of between-population differentiation to total diversity, the genetic effects of metapopulation processes may be difficult to interpret in terms of F(ST) on its own, so that the analysis of absolute measures of diversity in addition is likely to be informative. While population turnover may either increase or decrease F(ST), depending on the mode of colonization, recurrent extinction and recolonization is expected always to reduce levels of both within population and species-wide diversity (piS and piT, respectively). One corollary of this is that piS cannot be used as an unbiased estimate of the scaled mutation rate, theta, as it can, with some assumptions about the migration process, in species whose demes do not fluctuate in size. The reduction of piT in response to population turnover reflects shortened mean coalescent times, although the distribution of coalescence times under extinction colonization equilibrium is not yet known. Finally, we review current understanding of the effect of metapopulation dynamics on the effective population size. PMID- 11205347 TI - An adaptive model of sensory integration in a dynamic environment applied to human stance control. AB - An adaptive estimator model of human spatial orientation is presented. The adaptive model dynamically weights sensory error signals. More specific, the model weights the difference between expected and actual sensory signals as a function of environmental conditions. The model does not require any changes in model parameters. Differences with existing models of spatial orientation are that: (1) environmental conditions are not specified but estimated, (2) the sensor noise characteristics are the only parameters supplied by the model designer, (3) history-dependent effects and mental resources can be modelled, and (4) vestibular thresholds are not included in the model; instead vestibular related threshold effects are predicted by the model. The model was applied to human stance control and evaluated with results of a visually induced sway experiment. From these experiments it is known that the amplitude of visually induced sway reaches a saturation level as the stimulus level increases. This saturation level is higher when the support base is sway referenced. For subjects experiencing vestibular loss, these saturation effects do not occur. Unknown sensory noise characteristics were found by matching model predictions with these experimental results. Using only five model parameters, far more than five data points were successfully predicted. Model predictions showed that both the saturation levels are vestibular related since removal of the vestibular organs in the model removed the saturation effects, as was also shown in the e xperiments. It seems that the nature of these vestibular-related threshold effects is not physical, since in the model no threshold is included. The model results suggest that vestibular-related thresholds are the result of the processing of noisy sensory and motor output signals. Model analysis suggests that, especially for slow and small movements, the environment postural orientation can not be estimated optimally, which causes sensory illusions. The model also confirms the experimental finding that postural orientation is history dependent and can be shaped by instruction or mental knowledge. In addition the model predicts that: (1) vestibular-loss patients cannot handle sensory conflicting situations and will fall down, (2) during sinusoidal support-base translations vestibular function is needed to prevent falling, (3) loss of somatosensory information from the feet results in larger postural sway for sinusoidal support-base translations, and (4) loss of vestibular function results in falling for large support-base rotations with the eyes closed. These predictions are in agreement with experimental results. PMID- 11205348 TI - Neural network analysis of the pattern of functional connectivity between cerebral areas in schizophrenia. AB - Recent evidence suggests that the core abnormality of cerebral function in schizophrenia is a disruption of functional connectivity between diverse cerebral sites. Functional connectivity is defined as the correlation between neuronal activity at remote sites. It can be measured using functional imaging techniques such as positron emission tomography (PET). This paper reports an analysis using a neural network to discriminate between the patterns of functional connectivity in schizophrenic patients and healthy subjects. The data was derived from a PET study of regional cerebral blood flow during word generation in 6 healthy subjects and 16 schizophrenic patients with established illness, in whom the clinical diagnosis could be made with confidence. After training on data from two healthy subjects and seven schizophrenic patients, the neural network successfully assigned all members of a test set of four healthy subjects and nine schizophrenic patients to the correct diagnostic category. While this result should be interpreted with caution on account of the small sample size, it indicates that neural network analysis is potentially of value in the diagnosis of schizophrenia. PMID- 11205349 TI - Hippocampal rhythm generation: gamma-related theta-frequency resonance in CA3 interneurons. AB - During different behavioral states different population activities are present in the hippocampal formation. These activities are not independent: sharp waves often occur together with high-frequency ripples, and gamma-frequency activity is usually superimposed on theta oscillations. There is both experimental and theoretical evidence supporting the notion that gamma oscillation is generated intrahippocampally, but there is no generally accepted view about the origin of theta waves. Precise timing of population bursts of pyramidal cells may be due to a synchronized external drive. Membrane potential oscillations recorded in the septum are unlikely to fulfill this purpose because they are not coherent enough. We investigated the prospects of an intrahippocampal mechanism supplying pyramidal cells with theta frequency periodic inhibition, by studying a model of a network of hippocampal inhibitory interneurons. As shown previously, interneulrons are capable of generating synchronized gamnma-requency action potential oscillations. Exciting the neurons by periodic current injection, the system could either be entrained in an oscillation with the frequency of the inducing current or exhibit in-phase periodic changes at the frequency of single cell (and network) activity. Simulations that used spatially inhomogeneous stimulus currents showed antiphase frequency changes across cells, which resulted in a periodic decrease in the synchrony of the network. As this periodic change in synchrony occurred in the theta frequency range, our network should be able to exhibit the theta-frequency weakening of inhibition of pyramidal cells, thus offering a possible mechanism for intrahippocampal theta generation. PMID- 11205350 TI - Analysis of the reflexive feedback control loop during posture maintenance. AB - In previous work it has been shown in posture experiments of the human arm that reflexive dynamics were substantial for narrow-band stochastic force disturbances. The estimated reflex gains varied substantially with the frequency content of the disturbances. The present study analyses a simplified linear model of the reflexive feedback control loop, to provide an explanation for the observed behaviour. The model describes co-activation and reflexive feedback. The task instruction 'minimize the displacements' is represented mathematically by a cost function that is minimized by adjusting the parameters of the model. Small amplitude displacements allow the system to be analysed with a quasilinear approach. The optimization results clarify the limited effectiveness of reflexive feedback on the system's closed-loop behaviour, which emanates from the time delay present in the reflex loops. For low-frequency inputs less than 5 Hz, boundary-stable solutions with high reflex gains are predicted to be optimal. Input frequencies near the system's eigenfrequency (about 5 Hz), however, would be amplified and result in oscillatory behaviour. As long as the disturbance does not excite these frequencies, boundary stability will be optimal. The predicted reflex gains show a striking similarity with the estimated reflex gains from the experimental study. The present model analysis also provides a clear explanation for the negative reflex gains, estimated for near-sinusoidal inputs beyond 1.5 Hz. PMID- 11205351 TI - Optimal posture control of a musculo-skeletal arm model. AB - In this paper maximal performance posture control of the human arm is investigated by means of model simulations. Recent experiments (F.C.T. van der Helm, submitted, 2000) have shown that the reflexive feedback during postural control varies with the bandwidth of the applied force disturbances. This paper focusses on the influence of the frequency content of force disturbances on the reflexive feedback gains by means of optimization. The arm is modelled by a nonlinear musculo-skeletal model with two degrees of freedom and six muscles. To facilitate the optimization of the model parameters, the arm model is linearized. A performance criterion is minimized for stochastic force disturbances in a two step procedure: (1) optimization of static muscle activations using an additional energy criterion to obtain a unique and energy-efficient solution; antid (2) optimization of reflex gains using an additional control effort criterion to obtain a unique solution. The optimization reveals that for the given task and posture, the shoulder muscles have the largest contribution, whereas the bi articular muscles have a relatively small contribution to the behaviour. The dynamics at the endpoint level are estimated so that a comparison can be made with the experiments. Compared to the experiments, the intrinsic damping of the model is relatively large (about 150%), whereas the intrinsic stiffness is relatively small (about 60%). These differences can be attributed to unmodelled mechanical effects of crossbridges in Hill-type muscle models. The optimized reflex gains show remarkable similarities with the values found in the experiments, implying that humans can adjust their reflexive feedback gains in an optimal way, weighting the performance and energy. The approach in this paper could be useful in the study of various posture tasks, for example in the prediction of the relation between the control parameters of various musculo skeletal models and different experimental variables. PMID- 11205352 TI - The efficient learner. AB - The research to be reported examines the concept of efficiency, defined as the relation of metabolic energy expended to mechanical work done. The development of movement coordination was investigated in the context of the hypothesis that an increase in coordination would be accompanied by a parallel reduction in overall energy expenditure, relative to the increase in energy expenditure demanded by improvements in work output. The task involved learning to make cyclical, slalom like, ski movements on a ski apparatus. Development of coordination was indexed by changes in the timing of forcing while on-line measurements of oxygen consumption were used as indices of energy expenditure. Six female volunteers served as subjects in nine training sessions. The change in the coordination pattern, between the subject and the apparatus, as indexed by the development of the phase lag, was paralleled by an improvement in efficiency. It was concluded that learning the skill used in this study involves a search by the system for perception-action couplings (phase relations in the present study) that require minimal energy expenditure. PMID- 11205353 TI - High curvature and jerk analyses of arm ataxia. AB - We investigated high curvature analysis (HCA) and integrated absolute jerk (IAJ) for differrentiating healthy and cerebellopathy (CB) patients performing pointing tasks. Seventeen CB patients and seventeen healthy controls were required to move a pointer at their preferred pace between two 50.8 cm laterally spaced targets while standing with theirarm extended in front of their body. HCA was used to quantify the frequency of sharp turns in the horizontal-plane (anterior-posterior and medio-lateral) velocity trajectory of the hand-held pointer. IAJ was assesssed by integration of absolute jerk (second time derivative of velocity) time histories in the anterior-posterior and medio-lateral directions. HCA scores and IAJ scores were then compared between CB patients and healthy controls; for both analyses, higher scores indicateless smooth movements. We hypothesized that CB patients would have less smooth movement trajectories than healthy controls due to upper extremity ataxia asssociated with cerebellar disease and degeneration. We found that CB patients had higher HCA scores than healthy controls (P = 0.014). Although CB patients had higher IAJ scores in both anterior posterior (P = 0.060)and medio-lateral (P = 0.231) directions compared to the healthy controls, the differences were not significant. The difference in sensitivity between the HCA andthe IAJ analysis might be explained by primitive neural activation commands, ubiquitous though only evident with some cerebellar dysfunctions, which produce submovements which are themselves minimal jerk curves. We conclude that HCA may be a useful tool for quantifying upper extremity ataxia in CB patients performing a repeated pointing task. PMID- 11205354 TI - Dynamics of two electrically coupled chaotic neurons: experimental observations and model analysis. AB - Conductance-based models of neurons from the lobster stomatogastric ganglion (STG) have been developed to understand the observed chaotic behavior of individual STG neurons. These models identify an additional slow dynamical process calcium exchange and storage in the endoplasmic reticulum as a biologically plausible source for the observed chaos in the oscillations of these cells. In this paper we test these ideas further by exploring the dynamical behavior when two model neurons are coupled by electrical or gap junction connections. We compare in detail the model results to the laboratory measurements of electrically-coupled neurons that we reported earlier. The experiments on the biological neurons varied the strength of the effective coupling by applying a parallel, artificial synapse, which changed both the magnitude and polar-of the conductance between the neurons. We observed a sequence of bifarctions that took the neurons from strongly synchronized in-phase behavior. through uncorrelated chaotic oscillations to strongly synchronized and now regular out-of-phase behavior. The model calculations reproduce these observations quantitatively, indicating that slow subcellular processes could account for the mechanisms involved in the synchronization and regularization of the otherwise individual chaotic activities. PMID- 11205355 TI - The natural history of multiple sclerosis. AB - The natural history of chronic diseases is generally poorly understood. Multiple sclerosis is one of the best-studied diseases and we outline here some of the information obtained from 25,000 patient-years of observation. This population based cohort received almost no treatment and certainly none known to alter the long-term natural course of the illness. There is a possibility that such data will prove useful in new generation clinical trials which are observational in nature. PMID- 11205356 TI - Usefulness of Bayesian graphical models for early prediction of disease progression in multiple sclerosis. AB - Previous studies of possible prognostic indicators for multiple sclerosis have been based on "classic" Cox's proportional hazards regression model, as well as on equivalent or simpler approaches, restricting their attention to variables measured either at disease onset or at a few points during follow-up. The aim of our study was to analyse the risk of reaching secondary progression in MS patients with a relapsing-remitting initial course, using two different statistical approaches: a Cox's proportional-hazards model and a Bayesian latent variable model with Markov chain Monte Carlo methods of computation. In comparison with a standard statistical approach, our model is advantageous because, exploiting all the information gleaned from the patient as it is gradually made available, it is capable to detect even small prognostic effects. PMID- 11205357 TI - Age at onset in multiple sclerosis. AB - Age at onset of multiple sclerosis (MS) can vary from childhood to adult life. Many reports have been carried out over the years concerning the role of age at onset in determining the disease outcome. In a sporadic MS population of 1463 patients with homogeneous clinical and demographic features, derived from three Italian neurological centres (Bari, Cagliari and Sassari), we analysed the relative weights of current age and age at onset on disease severity according to the expanded disability status scale (EDSS) score, by fixing the disease duration. The results of present study demonstrate that clinical disability in MS is influenced by the patient's age (p < 0.01) and not by the age at onset. Therefore, these data do not confirm the hypothesis that an early age at onset should be considered a favourable prognostic factor of the disease outcome. PMID- 11205358 TI - A prospective study on the prognosis of multiple sclerosis. AB - Two hundred and twenty-four patients at their first diagnosis of multiple sclerosis (MS) were prospectively followed for a mean period of 9.78 years. We considered as endpoints the time to reach non-reversible disability levels corresponding to EDSS scores of 4.0 and 6.0, and the beginning of a secondary progressive phase in the relapsing-remitting subgroup of patients. An initially progressive course and higher basal EDSS scores proved to be the best predictors of unfavorable prognosis. A greater number of functional systems involved at onset as well as higher residual deficits in pyramidal, visual, sphincteric and cerebellar systems were other factors predictive of a poor outcome, whereas sensory system involvement turned out to be favorable. A longer first inter attack interval was associated with a better prognosis. However, overall number of relapses in the first two years of the disease was of no prognostic value. The presence of oligoclonal banding in the cerebrospinal fluid and a cerebral MRI exam strongly suggestive or suggestive of MS in the early phases of the disease were associated with a higher probability of a worse outcome. PMID- 11205359 TI - Prognosis of multiple sclerosis: environmental factors. AB - Epidemiological data have suggested a role for environmental factors in multiple sclerosis etiology. Infectious diseases, exposure to toxins, immunizations, nutritional and hormonal variables, and trauma are the most studied and biologically plausible risk factors for MS. Their putative role in determining or simply triggering MS development in genetically prone subjects suggests a possible involvement of the same factors in modulating the subsequent behavior of the disease and its prognosis. PMID- 11205360 TI - Is multiple sclerosis severity a genetically influenced trait? AB - Multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system of unknown pathogenesis, is a complex disease with a multifactorial etiology determined by both genetic and environmental factors. The pathological entity MS has a wide phenotype, and also the severity of the disease is widely variable. Clinical heterogeneity of the disease might arise from different genotype-phenotype interactions. Results of recent studies and theories about the modifying role of different genes in the course and the severity of MS are here discussed. PMID- 11205361 TI - Trauma, stress and multiple sclerosis. AB - It has been suggested that physical trauma, involving the cervical spinal cord or the brain, and psychological stress may precede MS onset or may influence the disease course, although this hypothesis has mainly come from anecdotal case reports or small uncontrolled or controlled studies. So far there are no studies providing a clear causative relationship between physical trauma (especially head trauma) and MS onset, exacerbation or progression of the disease. On the other hand, recent MRI and experimental studies, supporting the important role of nervous and immune system interactions, particularly by the hypothalamic pituitary-adrenal axis and by the sympathetic nervous pathways, seem to demonstrate a significant correlation between stress and MS exacerbations. Further frequent MRI and immunological evaluations should be warranted to objectively document the temporal association between stress and clinical and/or sub-clinical disease activity. PMID- 11205362 TI - Prognostic factors in multiple sclerosis: role of intercurrent infections and vaccinations against influenza and hepatitis B. AB - Since the first historical description of multiple sclerosis (MS) it has been known that febrile illnesses frequently trigger relapses of the disease. In spite of this knowledge, vaccination against influenza has been hampered for a long period by neurologists on the basis of anecdotal cases of post-vaccination encephalomyelitis. Randomized, double-blind, placebo-controlled studies during the past decade have shown that influenza vaccination of MS patients neither increases the relapse rate nor worsens the course of the disease. In contrast, the reduction of viral infection episodes leads to a lower number of exacerbations of MS. Influenza vaccination is safe and should be recommended to MS patients in order to avoid attacks of the disease. After publication of case reports of hepatitis B (HB) vaccination followed by onset of MS, a media-driven scare campaign mainly in France was conducted. The French health authorities decided to suspend routine vaccination of adolescents in schools, invoking the "principle of precaution". This fact has caused widespread confusion and concern about the HB vaccination. Epidemiological studies in large populations have recently been performed to investigate a possible link between HB vaccination and MS: all results argue against a causal relation between HB vaccine and MS or other demyelinating diseases. Since the vaccination provides complete protection against hepatitis B and its severe long-term complications, the World Health Organization recommends continuing the implementation of the HB vaccination programs. PMID- 11205363 TI - The prognostic value of age, gender, pregnancy and endocrine factors in multiple sclerosis. AB - The evolution of multiple sclerosis at the time of diagnosis remains unpredictable since a reliable prognostic marker is not yet available. Nevertheless, a series of useful prognostic indicators have been singled out from epidemiological studies. Young age at onset, female gender, relapsing/remitting course, and sensitive or visual disturbances as initial symptoms are considered favourable prognostic factors. Conversely, late age at onset, male gender, progressive course, and pyramidal or cerebellar symptoms at the first episode predict an unfavourable evolution. Another prognostic indicator has been recognized in pregnancy: although the overall effect of pregnancy on short-term MS course is neutral, in the long-term it seems to protect from disease progression. Most prognostic indicators seem to act through the neuro-endocrine immune network, modulating the immune response in the context of the Th1/Th2 paradigm. PMID- 11205364 TI - Early onset multiple sclerosis. AB - Multiple sclerosis (MS) onset is usually in adult life (age 20-40 years). Discordant data have been reported concerning the frequency of early onset MS (EOMS) that ranges from 2.7% to 5%, whereas there is a general agreement on prevalence of female sex, particularly after puberty. The initial symptoms in EOMS are frequently characterized by visual loss whereas the other functional systems are involved with a variable frequency. Literature data show that EOMS tends to have a relapsing-remitting course, a high rate of recovery from the initial attack, a long time interval between the first and second attacks and a slow progression rate. A poor prognosis is reported in a few cases of EOMS and seems to be related to number of relapses and to the delay between the first and second attacks. PMID- 11205365 TI - The prognosis of idiopathic optic neuritis. AB - We evaluated the risk of developing clinically definite multiple sclerosis (CDMS) after acute isolated optic neuritis in 102 patients in a follow-up study (duration 6.5 +/- 2.0 years). The probability of CDMS was 13% after 2 years, 30% after 4 years, 38% after 6 years, and 49% after 8 and 10 years. CDMS occurred in 42 (59%) of 71 patients with brain lesions detected with magnetic resonance imaging (MRI). No patient with normal MRI exam developed the disease. Patients with 3 or more MRI-detected lesions presented a shorter first interattack interval and a higher relapse rate compared to subjects with only 1 or 2 lesions. The predictive value of CSF examination and of evoked potentials was poor. PMID- 11205366 TI - Immunological markers in multiple sclerosis. AB - Multiple sclerosis (MS) is characterized by the presence in the central nervous system (CNS) of perivascular inflammatory infiltrates containing, among others, autoreactive T cells and activated macrophages. These observations indicate that MS is a T cell-mediated CNS-confined chronic inflammatory demyelinating disease in which the ultimate effector cell is the activated macrophage. The inflammatory process, leading to patchy demyelination and axonal loss, is mainly sustained by pro-inflammatory cytokines that, along with chemokines, adhesion molecules and metalloproteases, modulate at different levels the pathogenic process underlying MS. Due to their central role in MS pathogenesis, "inflammatory" molecules might represent suitable peripheral markers of disease (disease-trait) and/or disease activity (state-trait). However, reliable disease-trait or state-trait immunological markers for MS have not yet been identified. The intrinsic characteristics of these molecules (i.e. autocrine/paracrine activity, short half life, redundancy) may in part explain their inconsistency as disease markers. Additionally, the unreliability of methodologies and the lack of careful patient stratification can also, at least in part, account for the unsatisfactory results so far obtained. PMID- 11205367 TI - The role of magnetization transfer and diffusion-weighted MRI in the understanding of multiple sclerosis evolution. AB - Conventional magnetic resonance imaging (MRI) has markedly increased our ability to detect the macroscopic abnormalities of the brain and spinal cord in patients with multiple sclerosis (MS). Magnetization transfer imaging and diffusion weighted imaging have the potential to provide relevant and complementary information on the structural changes occurring within and outside these lesions and are contributing significantly to our understanding of the mechanisms leading to the accumulation of irreversible neurological disability in MS patients. The present review will summarize the major results achieved with the application of these two MR techniques to the assessment of the evolution of MS. PMID- 11205368 TI - Imaging axonal damage in multiple sclerosis by means of MR spectroscopy. AB - Axonal damage in multiple sclerosis has become an important issue. This has been emphasized by recent in vivo proton magnetic resonance (MR) spectroscopy and in vitro pathology studies that have found axonal damage in both lesions and the surrounding normal-appearing white matter. In particular, proton MR spectroscopy, by monitoring levels of N-acetylaspartate (a putative marker of axonal integrity), has been particularly illuminating, as the extent of axonal injury associated with white matter inflammation and demyelination had not been well appreciated from classical pathology studies. Recent MR data demonstrate that cerebral axonal damage begins and contributes to disability from the earliest stages of the disease. This implies that the apparently primary role of axonal damage and loss in the pathogenesis of the disease should be given due importance, and argues for the early treatment of multiple sclerosis with agents directed not only against inflammation, but also towards axonal protection. PMID- 11205369 TI - Evoked potentials in monitoring multiple sclerosis. AB - The usefulness of evoked potentials (EPs) in the diagnosis of multiple sclerosis is limited by its relatively low sensitivity to subclinical lesions. However, they are still a good tool to assess the integrity of afferent and efferent pathways and to quantify the severity of white matter involvement. Transversal and longitudinal studies have demonstrated good correlation between EP abnormalities and disability, suggesting that multimodal evoked potentials could be useful in monitoring the disease evolution in single patients and as surrogate end points in clinical trials. PMID- 11205370 TI - Prognosis-modifying therapy in multiple sclerosis. AB - The neurologist's views on disease therapy have changed over recent years from nihilism to reasonable optimism, thanks to the development of MS-specific therapies (interferon beta and COP-1) and to the remarkable advances in the understanding of the pathogenesis of the disease. Available immunological, clinical and pathological data suggest that the early treatment of RRMS patients with immunomodulatory drugs could be more advantageous compared to treatment started later in the disease course. The early reduction of relapse rate as well as of the extent of pathological lesions, should be the strategy for patients particularly in the first phases of the disease. Early treatment has a robust rationale both in prevention of irreversible pathological changes and in reducing clinical and MRI activity with favorable prognostic implications. For the near future, interferon beta and COP-1 seem to be the pharmacological agents best qualified to be utilized for this purpose. PMID- 11205371 TI - Joint Annual Meeting 2000 of the German and Dutch Societies of Immunology. Dusseldorf, November 29-December 2, 2000. Abstracts. PMID- 11205372 TI - Two-color flow cytometric analysis of preterm and term newborn lymphocytes. AB - Immune system maturation proceeds postnatally in humans. Therefore, newborns, especially those of a lower gestational age, are not fully immunocompetent and are more likely to acquire perinatal infections. In order to investigate the neonatal immune system status, the major lymphocyte subpopulations were studied in newborns of different gestational age, comparing term newborns and adults. The cord blood from 66 newborns and the peripheral blood from 23 adults were analyzed using fluorochrome labelled monoclonal antibodies and two-color flow cytometry. The newborns were divided into three groups according to their gestational age. Ten prematures were under 32 weeks of gestation, 35 were of 32-37 weeks and there were 21 term newborns. The percentage of cytotoxic T lymphocytes (CD4 CD8+) was lower in term newborns as compared to the adult controls (17.8 versus 30.3%), and so were the percentages of activated T lymphocytes (CD3+Ia+; 0.3 versus 3.7%), cytotoxic non-MHC restricted T lymphocytes (CD3+CD16+CD56+; 0.2 versus 1.8%) and NK cells (CD3-CD16+CD56+; 4.8 versus 15.5%). On the contrary, the proportions of unlabelled cells were increased in term cord blood. The expression of CD45R0 marker on neonatal lymphocytes was very low (1%). In comparison to the higher gestation newborns, the lower gestation prematures had reduced percentages of T lymphocytes (CD3+; 43 versus 65%), mostly helper T lymphocytes (CD4+CD8-; 35 versus 50%), and increased percentages of unlabelled cells. The percentages of NK cells (CD3+CD16+CD56+) and B lymphocytes (CD3-CD19+; CD3-Ia+) did not differ among the tested newborn groups. There were no significant differences in major lymphocyte subpopulations between the group of highest-gestation prematures and the group of term newborns that differed significantly when compared to adults. The lowest-gestation newborns showed the most immature lymphocyte phenotype with the highest percentages of unlabelled cells. PMID- 11205373 TI - Bifidobacterium adolescentis modulates the specific immune response to another human gut bacterium, Bacteroides thetaiotaomicron, in gnotobiotic rats. AB - In order to investigate the capability of an autochthonous bacterium to modulate the host's immune response against the indigenous microfiora, the immunogenicity of two selected bacterial species of the human gut was investigated in a gnotobiotic rat model. Germ-free (GF) rats were monoassociated with either Bifidobacterium (B.) adolescentis or Bacteroides (B.) thetaiotaomicron and the development of bacteria-specific IgG and IgA in serum and specific secretory IgA (sIgA) in feces of the animals were measured. Knowing the antibody levels in gnotobiotic rats induced by monoassociation, we subsequently diassociated two groups of rats in order to investigate the impact of B. adolescentis on the immune reaction against B. thetaiotaomicron. One group was diassociated simultaneously with B. adolescentis and B. thetaiotaomicron, the second group was diassociated with these bacteria in sequence. In contrast to B. thetaiotaomicron, B. adolescentis was not able to induce a systemic immune response in monoassociated animals as evident from serum IgG and IgA. However, both bacterial species challenged the mucosal immune system as indicated by an increase in sIgA in the feces. The specific immune response to B. thetaiotaomicron was significantly lower in diassociated animals than in animals monoassociated with B. thetaiotaomicron. This effect was more pronounced in the rats, that had been associated sequentially. The presence of B. adolescentis down-regulated the humoral immunity to B. thetaiotaomicron. PMID- 11205374 TI - Ineffective elimination of Leishmania major by inflammatory (MRP14-positive) subtype of monocytic cells. AB - Myeloid-related protein (MRP) 14, an intracellular protein involved in calcium dependent activation of myeloid cells, presents a differentiation marker for a subtype of macrophages. In experimental leishmaniasis, BALB/c mice succumb to visceral dissemination after infection with L. major, due to a Th2 cell response, while C57Bl/6 mice develop protective immunity associated with a Th1 cell response. We have previously shown that resistance in (C57Bl/6 mice was also associated with a significantly lower percentage of MRP14-positive cells in the infiltrate than in susceptible BALB/c mice. In C57Bl/6 mice, weekly injections of bone marrow (BM) cells enriched with MRP14-positive cells (d1 of culture) did not reverse, but prolonged the course of infection, associated with increased local parasite spread. In BALB/c mice a single dose of an antiphlogistic agent (dexamethasone or lipoxygenase inhibitor) was associated with reduction of infiltrating MRP14-positive cells and also with a decrease of parasite loads in footpads, lymph nodes as well as spleens, and with delayed progression of disease, Double labeling experiments in vitro revealed that at least 43.1% of MRP14-positive mononuclear cells in BM cultures (8h) had phagocytosed parasites after 4 h of co-incubation. Activation by IFN-gamma (20 U/ml) for 24h and 48h did not significantly reduce parasite load in these cells. In contrast, 77.0% of F4/80-positive macrophages (6d of culture) were infected with L. major parasites and these cells responded to activation with IFN-gamma (20 U/ml) with significant reduction of parasite load (25.3%). The protein MRP14 did not have an effect on parasite survival in vitro. Thus, the impaired capability of MRP14-positive cells to kill L. major upon stimulation may be one reason for the adverse course of infection observed with their increased appearance. PMID- 11205375 TI - Inflammation marker 7,8-dihydroneopterin induces apoptosis of neurons and glial cells: a potential contribution to neurodegenerative processes. AB - Since neopterin is elevated in the cerebrospinal fluid of patients with inflammatory neurological disorders we investigated the source of neopterin in the brain and a possible contribution of biological active pteridines to the development of brain lesions. Astrocytic, neuronal and microglial cell lines were shown to be negative for neopterin production even after stimulation with interferon-gamma (IFN-gamma) indicating that infiltrating monocytes/macrophages might be responsible for neopterin level in CNS. Whereas neopterin did not affect viability of brain cells, its derivative 7,8-dihydroneopterin (7,8-DHN) induced dose-dependently cellular apoptosis in astrocytes and neurons probably via enhancement of nitric oxide synthase (iNOS) expression. This mechanism might represent a possible link between inflammation in the brain and neurodegeneration. PMID- 11205376 TI - LPS stimulation of TNF-receptor deficient macrophages: a differential role for TNF-alpha autocrine signaling in the induction of cytokine and nitric oxide production. AB - To evaluate the role of autocrine TNF-alpha signaling in macrophage activation, immortalized macrophages from normal mice (B6/J2) and from mice containing gene targeted disruptions of the type 1 and type 2 TNF-receptor genes (TRN) were stimulated under CD14-dependent or serum-free conditions. Although the B6/J2 and TRN clones mounted similar nitric oxide responses to LPS in the presence of serum, the TRN macrophages responded poorly when stimulated with LPS under serum free conditions. LPS stimulation of TRN and B6/J2 under serum-free conditions resulted in equivalent levels of IL-1beta, TNF-alpha, and iNOS gene expression. However, Western blot analysis revealed that iNOS protein production by TRN was 2 fold lower than that produced by B6/J2. These results indicate that autocrine TNF alpha stimulation contributes to the signaling pathways initiated by ligation of LPS receptors in the absence of LBP and is involved in iNOS post-transcriptional regulation. PMID- 11205377 TI - Superantigen-dependent accelerated death of bovine neutrophilic granulocytes in vitro is mediated by blood mononuclear cells. AB - While classical interactions of bacterial superantigens (SAgs) with antigen presenting cells and T cells have been studied intensively, the potential interactions of SAgs with granulocytes (PMNs) have gained much less attention. We investigated if in the bovine system SAgs have any direct or indirect influence on the fate of granulocytes, which are among those cells primarily responsible for the elimination of superantigen-producing bacteria. The tested SAgs (SEA, SEB) had no apparent direct effect on PMN viability (neutrophils and eosinophils). However, in the presence of blood mononuclear cells (MNCs), SAgs led to an accelerated death of neutrophils but not of eosinophils. Compared to medium controls, in SAg-stimulated cultures only about 20-50% of the neutrophils survived after 24 hours in vitro. Accelerated death of neutrophils required the presence of at least 10% MNC and started between 2.5-24 h after initiation of the co-culture between MNC and PMN. Minimal effective SEA concentrations ranged between 10-100 pg/l (SEB 0.1-10 ng/l). The effect could be mimicked by culture supernatants of SAg-stimulated MNCs, suggesting that direct cell-cell interactions are not required for the killing. In the human system, where we tested the role of TNF-alpha, an antibody specific for this cytokine was not able to abolish the death of human neutrophils. Brefeldin A, an inhibitor of golgi transport and cytokine secretion, which blocked the SAg-induced activation of bovine MNC did not abolish the killing of neutrophils. Blocking of nitric oxide generation or PGE2 synthesis also could not alter the SAg-induced killing of bovine neutrophils. The observed indirect negative effects of SAgs on neutrophils may provide new insights in mechanisms by which superantigens modulate the hosts immune response. PMID- 11205378 TI - Superantigen disruption of CD8+ T and B lymphocyte homeostasis. AB - Superantigens (SAgs) activate TH cells and induce their differentiation into cytokine-producing effector cells. Supranormal cytokine production is characteristic of SAg-induced polyclonal TH activation. Study of this interaction has focused upon TH cell function to the relative exclusion of other lymphocyte populations. SAgs also impact cells dependent upon TH cells for their differentiation and disrupt the normal homeostasis of the immune system. In this report, several changes in lymphocyte biology that result from SAg activation of TH cells are described. SCID mice, reconstituted with the SAg-expressing cells of DBA/2J mice, were employed as secondary recipients of SAg-reactive TH cells. Significant increases in serum IgM and IgG2a production were noted after the transfer of SAg-reactive It cells. Both B and CD8 T lymphocyte numbers increased with those of CD8 T cells surpassing levels found in normal mice. These results illustrate the ability of the TH-SAg interaction to disrupt B and CD8+ T lymphocyte homeostasis. PMID- 11205379 TI - Contact dermatitis from white flower embrocation. PMID- 11205380 TI - Fixed drug eruption due to scopolia extract. PMID- 11205381 TI - Hyperpigmentation and contact dermatitis due to Juglans regia. PMID- 11205382 TI - Allergic nickel and chromate hand dermatitis induced by orthopaedic metal implant. PMID- 11205383 TI - Allergic contact dermatitis from benzocaine ointment during treatment of herpes zoster. PMID- 11205384 TI - Unusual clinical presentation in a case of contact dermatitis due to corticosteroids diagnosed by ROAT. PMID- 11205385 TI - Eczema herpeticum in parthenium dermatitis. PMID- 11205386 TI - Aziridine hardener--a new sensitizer in the dyeing of leather. PMID- 11205387 TI - Occupational allergic contact dermatitis from formaldehyde resin in clothing. PMID- 11205389 TI - Dermatitis around tracheostomies due to cleansing tissues. PMID- 11205388 TI - Localized aquagenic urticaria dependent on saline concentration. PMID- 11205390 TI - Allergic contact dermatitis from estradiol and norethisterone acetate in a transdermal hormonal patch. PMID- 11205391 TI - Erythema-multiforme-like eruption from amoxycillin and allopurinol. PMID- 11205392 TI - Acute generalized exanthematous pustulosis induced by amoxycillin with clavulanate. PMID- 11205393 TI - Allergic contact dermatitis due to guava tea. PMID- 11205394 TI - Optician's occupational allergic contact dermatitis, paresthesia and paronychia caused by anaerobic acrylic sealants. PMID- 11205395 TI - Allergic contact dermatitis from zinc ricinoleate in a deodorant and glyceryl ricinoleate in a lipstick. PMID- 11205396 TI - 182 patients with occupational allergic epoxy contact dermatitis over 22 years. PMID- 11205397 TI - Increase in hydration and protective function of horny layer by glycerol and a W/O emulsion: are these effects maintained during long-term use? PMID- 11205398 TI - Chemical load as a factor in skin sensitization risk assessment: rodent versus man. PMID- 11205399 TI - Contact allergy to miripirium chloride in Depo-Medrol. PMID- 11205400 TI - Contact dermatitis from sodium metabisulfite in a baker. PMID- 11205401 TI - Recalcitrant allergic contact dermatitis from azathioprine tablets. PMID- 11205402 TI - Occupational sensitization to methoxysilane in fibreglass production. PMID- 11205403 TI - Sensitive skin is not a subclinical expression of contact allergy. PMID- 11205404 TI - Osmaron B is a rare occupational, but a frequent cosmetic, allergen. PMID- 11205405 TI - Legislative and preventive measures related to contact dermatitis. AB - Legislation can be a useful tool in the prevention of contact dermatitis. This is particularly true for dermatitis due to exposure to the many contact allergens that are chemical substances in products. A brief review is given of the most important European legislation--the EU Nickel Directive, the Cosmetics Directive, the Hazardous Substances Directive and the Hazardous Preparations Directive--and of some national regulations and standardization projects. It is concluded that it is essential that experts on contact dermatitis support, with their expert knowledge, national and European authorities. PMID- 11205406 TI - Investigation of the threshold for allergic reactivity to chromium. AB - Allergy to chromium is relatively common, often in association with exposure to cement or in leather manufacture. However, in certain locations, there appears to be a relatively large cohort of chromium-sensitive individuals whose allergy cannot be explained by these common sources. In particular, this group include Israeli housewives with persistent hand eczema and concomitant patch test positivity to chromium. The causation of their allergy has been linked with relatively high levels of chromium contamination in household products. To provide further information in respect of the definition of safe levels for such products, we examined 17 chromium-allergic individuals to determine their threshold for reaction under closed patch test and repeated open application test (ROAT) conditions. The data derived indicated that, on normal skin, the patch test threshold was 10 ppm chromium; in the presence of an irritant (sodium lauryl sulfate) the threshold was closer to 1 ppm, 2/17 subjects giving 1+ reactions at this concentration. In the more realistic exposure conditions of the ROAT, 8/14 individuals failed to react to 50 ppm, whilst 3/15 reacted to 5 ppm. Interestingly, there was very poor correlation between patch test sensitivity and ROAT sensitivity. To ensure the large majority of chromium-allergic individuals do not suffer elicitation of their allergy, as well as to limit the development of new chromium-sensitive subjects, it is recommended that household products adhere to a previously published standard of a maximum limit of 5 ppm, with an ultimate target of 1 ppm contamination by chromium. PMID- 11205407 TI - Reduction of use of latex gloves in food handlers: an intervention study. AB - Frequent latex glove use is a risk factor for the development of latex allergy. With the increase in latex glove use, latex allergy has become more prevalent. There are a number of occupational groups in which the use of latex gloves is both inappropriate and even hazardous, including food handlers, where the hazard relates particularly to their latex-sensitive customers. The aim of this study was to assess both the use of latex gloves by food handlers and the impact of an intervention study on reducing latex glove use. This was done at the Queen Victoria Market in Melbourne, Australia. We found that 10 out of 30 stalls (33%) used latex gloves, and that following a short education program, this was reduced to 1 stall (3%, p=0.006). The potential to reduce latex glove use by using this intervention study was 93% (95% confidence interval of 54%-100%). We recommend that food handlers be educated during their training, not only about hygiene issues, but also about the appropriate type of glove to wear, in order to prevent both the development of a new occupational group at risk of becoming allergic to latex, but more importantly to protect their latex-sensitive customers. PMID- 11205408 TI - Results of a quality of life questionnaire in a patch test clinic population. AB - There has been increasing interest in quality of life outcomes, but there has been little reported on this topic for individuals with contact dermatitis. The objectives of this study were (i) to pilot a dermatology-specific quality of life instrument to assess its acceptability in a patch test clinic population, (ii) to see the effects of contact dermatitis on the patients' lives and (iii) to determine what factors may influence quality of life outcomes in this population. A dermatology-specific quality of life instrument was modified and used for 339 patients undergoing patch testing in a contact dermatitis clinic. The most common effect was pain or itching in 61%. Approximately 1/3 noted embarrassment, interference with work, or sleep disturbance. Other concerns were reported by less than 25% of the population. On multivariate analysis, the key factor influencing most outcomes was hand involvement. The instrument was well accepted by the clinic population and is now being used in a prospective study of outcomes. In the population assessed, it demonstrated the effects of disease. Analysis suggests that a key factor influencing these quality of life outcomes is hand involvement. PMID- 11205409 TI - The prevention of occupational hand dermatitis in bakers, confectioners and employees in the catering trades. Preliminary results of a skin prevention program. AB - Occupational skin diseases (OSD) are among the most frequent occupational diseases (OD). Compared to other occupations, bakers, confectioners and employees in the catering trades are at a high risk of developing OSD. In January 1999, the interdisciplinary Skin Disease Prevention Program in the Baking, Hotel and Catering Industries (SDPP) conducted by the Department of Dermatology and Allergology at the Friedrich Schiller University, Jena, in cooperation with the Research Center for Applied System Safety and Industrial Medicine, Erfurt, and the technical experts at the Social Insurance for the Food Industry and Related Professions (Berufsgenossenschaft fur Nahrungsmittel und Gaststatten--(BGN)), Erfurt, was initiated. Following detailed analysis of the occupational exposure of the employees and their personal occupational disease history, the patients' diagnosis and therapy was re-evaluated and supplemented if necessary. Individual skin care and protection regimes were demonstrated and practically trained. Skin care and protection products were supplied. Skin-care and protection seminars were offered to volunteering participants. From January to December 1999, 29 affected employees were examined in the OSD clinic. 22 employees (76%) suffered from irritant contact dermatitis. The follow-up data of 11 employees are available. In 8 employees (73%), the skin disease improved or disappeared. Moreover, in 1 employee (9%), the skin condition was stabilized even though he continued working. In only 2 employees (18%) did the skin condition worsen. These preliminary results showed that most of the OSD were due to lack of or unsuitable skin care and protection. The program will be extended to cover a larger number of food industry employees with OSD. PMID- 11205410 TI - Occupational skin diseases in national servicemen and military personnel in Singapore, 1989-1999. AB - This is a study of occupational skin disease among military personnel and conscripts in Singapore. All military personnel and conscripts diagnosed with occupational dermatoses in the National Skin Centre, Singapore, between 1989-1999 were studied retrospectively. Conscripts and regulars comprised 7.3% of all occupational skin disease patients seen. All were male, with a mean age of 23 years. Irritant contact dermatitis was more common than allergic contact dermatitis, by 4.4:1. The most common vocations associated with occupational skin diseases are those involving vehicle repairs and maintenance (48%) and food handling (19%). The most common irritants were oil/grease (66%), wet work (23%) and solvents (18%). The most common allergens were food (40%) and chromates (20%). Military personnel and conscripts make up a significant proportion of occupational skin disease patients seen in Singapore. PMID- 11205411 TI - Contact urticaria from rice. AB - A 30-year-old man with atopic dermatitis had had erythema and itching of the hands after washing rice in water, though he had always eaten cooked rice without problems. Handling test with water used to wash regular rice was performed on abraded hands, and produced urticarial erythema after several minutes. Applications of water used to wash allergen-reduced rice were negative for urticarial reaction. Prick test with water used to wash regular rice was +++. However prick test reaction with water used to wash allergen-reduced rice was +. Histamine-release test of regular rice-washing water was grade 3 and that of allergen-reduced rice grade 1. In immunoblotting analysis with regular rice washing water, there were no bands with this patient. These results suggest that the allergen responsible for contact urticaria in this patient might be water soluble, heat-unstable, and not contained in allergen-reduced rice. PMID- 11205412 TI - Irritant contact dermatitis caused by needle-like calcium oxalate crystals, raphides, in Agave tequilana among workers in tequila distilleries and agave plantations. AB - It was found that needle-like calcium oxalate crystals, raphides, are found abundantly in all tissues of Agave tequilana plants; thus, 1 droplet (0.03 ml) of juice pressed from leaves contains 100-150 crystals, 30-500 microm in length, sharpened at both ends. In tequila distilleries, 5/6 of the workers who handle the agave stems have experienced the characteristic irritation. In contrast, only 1/3 of workers in agave plantations who harvest agave plants, complain of the irritation. It is confirmed that all the irritation suffered in both distilleries and plantations takes place at bodily locations where the plants come into contact with the worker's skin in the course of their work. PMID- 11205413 TI - Allergic contact dermatitis at the application site of an electrosurgical earthing plate occurring in a windscreen repairer. PMID- 11205414 TI - Contact allergy to epoxy resin based on diglycidyl ether of bisphenol F. PMID- 11205415 TI - What is a "low dose" of d-amphetamine for inducing behavioral effects in laboratory rats? AB - BACKGROUND: Because of the amphetamines' abuse potential and capability of exacerbating or inducing mood and psychotic disturbances, investigations of the behavioral effects of amphetamines commonly involve non-human animals, with the laboratory rat being by far the most common species used. Although investigators of the behavioral effects of amphetamine in rats sometimes refer to doses used as being "low", "moderate", "high", etc., it is not clear in what sense these terms apply. OBJECTIVES: To develop an operational definition of a low dose of amphetamine in rats, we reviewed studies that assessed the behavioral effects of dextroamphetamine (d-AMP) in rats in which some subset of doses, administered SC, IM or IP, was described as being "low". We then used the results of these studies to establish what the lowest effective dose ranges were across a variety of behavioral domains and compared these doses and their effects with those obtained with normal, healthy adult humans. RESULTS: While the range of the lowest doses used in the studies with rats was quite broad (0.025-2.0 mg/kg), the median lowest effective doses observed (in the studies using doses of 0.125 mg/kg or less) were between 0.125 and 0.165 mg/kg across the behavioral domains of consummatory behavior, unconditioned or spontaneous behavior, learned behavior, and drug discriminative control. This range of doses was also found to be comparable to the lowest behaviorally effective doses of d-AMP (SC or PO) in normal human adults, which suggests that the sensitivity to the behavioral effects of amphetamine in these two species is fairly comparable. CONCLUSIONS: Because of their ability to alter a wide variety of behaviors in rats, we conclude that low doses of d-AMP are in the 0.1-0.4 mg/kg range. Doses within this range typically: 1) constitute the ED50 in most drug discrimination/generalization procedures; 2) increase a variety of consummatory behaviors; 3) increase a variety of unconditioned or spontaneous motor activities; 4) increase low rate schedule-controlled behavior while exerting variable effects on high rate schedule controlled behavior; and 5) improve performance on some choice tasks, particularly those requiring sustained attention. Our analyses also indicate that, with respect to behavior, investigators do not always agree on what constitutes a low dose of amphetamine in rats and that doses assumed to be low for this species often are relatively high. PMID- 11205416 TI - Involvement of D2 dopamine receptors in the opposing effects of two CCK-B agonists in a spatial recognition memory task: role of the anterior nucleus accumbens. AB - RATIONALE: A previous study in the rat has shown that systemic injection of two CCK-B agonists, BC264 and BC197, induced opposing effects on the retrieval phase of a spatial recognition memory task. OBJECTIVE: The present study was designed to investigate the mechanisms underlying these effects at the level of the dopaminergic system. METHODS: Rats were injected IPly with BC264 (0.3 microg/kg) or BC197 (30 microg/kg) and with D1 or D2 agonists and antagonists. The cognitive performances of rat were analysed on the retrieval phase of a spatial recognition memory task. The extracellular levels of dopamine were quantified in the anterior nucleus accumbens after injection of BC197 (3, 30 and 300 microg/kg IP), using the microdialysis technique on freely moving rats. Local injection of the D2 antagonist, sulpiride (2.5 ng/microl) was performed in the anterior nucleus accumbens and the cognitive performances analysed following systemic injection of BC264 (0.3 microg/kg). RESULTS: The improvement and the impairment of performance induced respectively by BC264 and BC197 were suppressed by peripheral administration of sulpiride, showing that these opposing effects were both mediated by the stimulation of D2-like receptors. However, different dopaminergic pathways seem to be involved in the effects of the two CCK-B agonists. Indeed, systemic administration of BC197 did not induce the increase of extracellular dopamine levels observed with BC264. Furthermore, local injection of sulpiride, in the anterior nucleus accumbens, completely suppressed the cognitive enhancing effect of BC264. CONCLUSION: These findings suggest that the D2-mediated deficit in the performance induced by BC197 involves brain structures other than the anterior nucleus accumbens. They also demonstrate a critical role of dopaminergic transmission within the anterior nucleus accumbens in the improving effect induced by BC264 in a spatial memory task. PMID- 11205417 TI - Pain and negative affect: evidence the inverse benzodiazepine agonist DMCM inhibits pain and learning in rats. AB - RATIONALE: The anxiogenic DMCM, an inverse benzodiazepine agonist, was used to explore the relationship between negative affective states and pain. Past work suggests that the outcome obtained may depend on both the intensity of the affective state and the way in which pain is inferred. OBJECTIVES: The present study was designed to test the impact of relatively low doses of DMCM on multiple measures of pain reactivity and learning. METHODS: In experiment 1, systemic injections of 0.00, 0.015, 0.06, and 0.25 mg/kg DMCM were administered before vocalization and tail movements were assessed in response to a gradually incremented shock and radiant heat stimulus. Experiment 2 tested the effects of DMCM on Pavlovian conditioning. DMCM-treated subjects experienced a context paired with an aversive unconditioned stimulus (US) and conditioned freezing was assessed the next day. RESULTS: Experiment 1 showed that DMCM inhibits both a spinal nociceptive reflex (tail-flick to heat) and a supraspinal measure of pain (vocalization to shock). Because these inhibitory effects could reflect a disruption in motor function, experiment 2 employed a remote test based on Pavlovian conditioning. A moderate dose of DMCM undermined learning, implying that the drug decreased the affective impact of the aversive US. CONCLUSIONS: DMCM induces hypoalgesia on a wide range of assays. Furthermore, pharmacologically inducing a negative affective state blocks Pavlovian fear conditioning. It is suggested that DMCM induces a state of panic and that this state inhibits pain. PMID- 11205418 TI - Scopolamine fails to diminish chronic haloperidol-induced purposeless chewing in rats. AB - Chronic haloperidol treatment for 4-12 months gradually induces spontaneous, irregular, purposeless oral chewing movements (CMs), apparently involuntary, in some but not all treated rats. Based on phenomenologic and pharmacologic similarities, this laboratory preparation has been used as an animal model of tardive dyskinesia (TD), which is the human hyperkinetic motor syndrome associated with chronic antipsychotic administration. This putative animal model has received the most severe challenge to its validity by claims that its oral movements can be suppressed by anticholinergic treatments, since resistance to anticholinergic suppression is an accepted pharmacologic feature of TD. In this experiment, we challenged a group of haloperidol-treated rats with CMs using three doses of scopolamine (0.1, 0.3, 1.0 mg/kg) and placebo and rated the change in dyskinetic movements. Each scopolamine dose reduced CMs by a similar magnitude, without any dose effect; the saline dose also reduced CMs to an equivalent degree. Therefore, we concluded that some component of the experiment, not the scopolamine, reduced the CMs. The handling component of the procedure was identified as a likely confound, and we tested this further. Rats with CMs were handled at several levels of "severity"; and the dyskinesias were rated at 1 and 3 h later. CMs were reduced by the experimental handling, in relation to the strength of the handling. Minimal handling produced modest CM reductions with quick recovery; whereas, the "strongest" handling plus the placebo injection produced the greatest CM reduction, evident over 3 h, resembling the CM reductions seen in the scopolamine and placebo experiment. Overall, these results suggest that anticholinergic drugs do not suppress chronic haloperidol-induced rat CMs. However, the movements are sensitive to stressful handling situations, and diminish with stress. In both of these characteristics, rat CMs resemble human TD, further supporting a role for this model in studies of human TD. PMID- 11205419 TI - Cognitive performance and serotonergic function in users of ecstasy. AB - RATIONALE: (+/-) 3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") has been shown to cause long term damage to serotonergic cerebral neurons in animals. The neurotoxic effects in humans are less clear and little is known about the functional consequences, although some studies suggest memory impairment. Given the widespread use of MDMA, our lack of knowledge raises concerns. OBJECTIVE: We investigated, in humans, the relation between past use of ecstasy and cognitive performance as well as serotonergic function. METHODS: Two groups of 21 males with moderate and heavy recreational use of MDMA, respectively, and a control group of 20 males without use of MDMA were compared. All were from the same subculture. Reaction time, direct recall, and recognition were assessed. Serotonergic function was measured by the neuro-endocrine response to a placebo controlled, crossover challenge with dexfenfluramine. RESULTS: Ecstasy users showed a broad pattern of statistically significant, but clinically small, impairment of memory and prolonged reaction times. Heavy users were affected stronger than moderate users. Release of cortisol but not of prolactin after dexfenfluramine administration was significantly reduced in both groups of ecstasy users compared with the controls. Analyses of covariance showed that likely confounding variables including recent exposure to ecstasy, psychosocial profiles and use of other drugs did not explain the differences found between the groups. CONCLUSIONS: These results provide further evidence that use of ecstasy may be associated with impairment of memory and of serotonergic function. These findings are compatible with neurotoxicity of ecstasy as shown in animals. PMID- 11205420 TI - Evidence that orexin-A-evoked grooming in the rat is mediated by orexin-1 (OX1) receptors, with downstream 5-HT2C receptor involvement. AB - RATIONALE: Orexins A and B have recently been discovered and shown to be derived from preproorexin, primarily expressed in the rat hypothalamus. Orexin-A has been ascribed a number of in vivo functions in the rat after intracerebroventricular (ICV) administration, including hyperphagia, neuroendocrine modulation and, most recently, evidence for a behavioural response characterised by an increase in grooming. OBJECTIVES: Here, we have investigated the orexin-receptor subtypes involved in the grooming response to orexin-A (3 microg, ICV) in the rat. METHODS: Male rats, habituated to clear Perspex behavioural observation boxes, were pretreated with antagonists with mixed selectivity for OX1, OX2, 5-HT2B and 5-HT2C receptor subtypes prior to the administration of orexin-A and the intense grooming response elicited by this peptide assessed. RESULTS: Pretreatment of rats with a mixed OX1/5-HT2B/2C receptor antagonist 1-(4-methylsulfanylphenyl)-3 quinolin-4-ylurea (SB-284422), revealed a significant, but incomplete, blockade of orexin-A-induced grooming. Despite the low potency of orexin-A at 5-HT2B and 5 HT2C receptors in vitro (pKi<5), studies were undertaken to determine whether downstream 5-HT2B or 5-HT2C receptors mediate in the grooming-elicited by orexin A. Whilst the selective 5-HT2B receptor antagonist, SB-215505 (3 mg/kg, PO, 5 HT2B, pKi=8.58; OX1, pKB < 5.15) failed to effect orexin-A-induced grooming, the selective 5-HT2C receptor antagonist, SB-242084 (1 mg/kg, IP, 5-HT2C, pKi = 8.95; OX1, pKB < 5.1) potently antagonised the grooming response to this peptide. This suggested that the partial blockade of orexin-A-induced grooming obtained with SB 284422 might be attributable to its 5-HT2C and/or OX1 receptor blocking activity. However, complete blockade of orexin-A-induced grooming by the subsequently identified selective OX1 receptor antagonist 1-(2-methylbenzoxazol-6-yl)-3 [1,5]naphthyridin-4-yl urea hydrochloride, SB-334867-A (OX1, pKB = 7.4; OX2, pKB = 5.7), devoid of appreciable affinity for either 5-HT2B (pKi < 5.3) or 5-HT2C (pKi < 5.4) receptors, provides the first definitive evidence that a central behavioural effect of orexin-A (grooming) is mediated by OX1 receptors. CONCLUSIONS: This data suggests that orexin-A indirectly activates 5-HT2C receptors downstream from OX1 receptors to elicit grooming in the rat. The use of SB-334867-A in vivo will enable the role of OX,1 receptors within the rat central nervous system to be further characterised. PMID- 11205422 TI - Anxiolytic properties of botanical extracts in the chick social separation-stress procedure. AB - RATIONALE: The recent growth in sales of natural products labeled as dietary supplements in the United States has renewed scientific interest in the study of the therapeutic effects of multi-component botanical products. OBJECTIVES: This study sought to determine whether botanical extracts derived from the Rutaceae family, Acori graminei, the Magnoliaceae family, Alchemilla vulgaris and Primula veris, which had previously been identified in bioassays as having potential anxiolytic activity, were active in the chick social separation-stress procedure. METHODS: Eight-day-old chicks received IP injections of test articles 30 min before being tested in the presence of two social companions or in isolation for a 3-min observation period. Dependent measures were: a) latency to adopt a ventral recumbent posture to index sedation, b) number of vocalizations to index separation-distress and c) a composite pain score (comprised of footlift frequency and footlift duration in response to 50 microl of 0.10% formalin injected into the plantar surface of the foot) to index stress-induced analgesia. RESULTS: Proprietal extracts NPS00033 from the Rutaceae plant family and NPS00039 (Relora) from the Magnoliaceae plant family screened positive in this chick model without causing sedation. CONCLUSIONS: These results suggest that botanical extracts Relora and NPS00033 may be useful in modulating anxiety states. PMID- 11205421 TI - Effects of centrally administered orexin-B and orexin-A: a role for orexin-1 receptors in orexin-B-induced hyperactivity. AB - RATIONALE: Orexin-A and orexin-B are hypothalamic neuropeptides derived from a 130-amino acid precursor, prepro-orexin, and are potent agonists at both the orexin-1 (OX1) and orexin-2 (OX2) receptors. Orexin-A has been ascribed a number of in vivo functions in the rat after intracerebroventricular (ICV) administration, including hyperphagia, neuroendocrine modulation and a role in the regulation of sleep-wake function. The in vivo role of orexin-B is not as clear. OBJECTIVES: To investigate the behavioural, endocrine and neurochemical effects of orexin-B in in-vivo tests. In a number of experiments, these effects were compared with those of orexin-A. METHODS: Experiments were carried out in male, Sprague-Dawley rats with a guide cannula directed towards the lateral ventricle. The effects of orexin-B (ICV) upon grooming behaviour were compared with those of orexin-A. The effects of orexin-B upon the motor activity response to both novel and familiar environments were assessed in an automated activity monitor. Orexin-B was tested upon startle reactivity and body temperature. Further, plasma hormones and [DOPAC+ HVA]/[DA] and [5-HIAA]/[5-HT] ratios in six brain areas were measured 40 min post-orexin-B or orexin-A. RESULTS: The clearest behavioural response to orexin-B was increased motor activity in both novel and familiar environments. Orexin-B-induced hyperactivity was blocked by an OX1 receptor antagonist, SB-334867-A, implicating OX1 receptors in this behavioural response. In common with orexin-A, orexin-B reduced plasma prolactin and failed to influence startle reactivity. However, in contrast with orexin-A, orexin-B increased head grooming but failed to cause a robust whole body grooming response or increase plasma corticosterone levels. Further, orexin-B, but not orexin-A, increased plasma TSH and increased hypothalamic and striatal [5-HIAA]/[5-HT] ratios. CONCLUSIONS: The present study has demonstrated a number of behavioural, neuroendocrine and neurochemical effects of orexin-B that distinguish it from orexin-A. Further, we have demonstrated a role for OX1 receptors in the actions of orexin-B upon motor activity. PMID- 11205423 TI - Individual differences in preferences for and responses to four nicotine replacement products. AB - RATIONALE: With several different forms of nicotine replacement therapy available for smokers, it is useful to know about factors that may influence choice of form. OBJECTIVE: To examine factors associated with preference for different nicotine replacement products and effectiveness of these products. The simple comparison of success rates between the products has been reported previously. METHODS: Five hundred and four smokers were invited to rank order four products (gum, patch, nasal spray and inhaler) in terms of preference and were then randomly allocated to receive one of the products for a smoking cessation attempt. They were followed up 1 week, 4 weeks, 12 weeks and 15 weeks later. Ratings of the products were repeated 1 week after the quit date. Mood and physical symptoms were assessed at baseline and at each follow-up visit. Urges to smoke were assessed at all post-quit date sessions. Abstinence was assessed by self-report with expired air carbon monoxide verification. RESULTS: The patch was the most popular product initially, followed by the spray and inhaler and then the gum. The difference was greater for women than men. However, all smokers quickly came to like whichever product they had been allocated. Smokers who initially preferred the spray or inhaler were heavier smokers than those who preferred the gum or patch. Prior experience of the gum was associated with lower initial preference for it, but did not affect outcome. Prior experience with the patch had no effect on preference or outcome. Being allocated to the preferred product did not increase success at stopping smoking. Women were more successful at stopping smoking on the inhaler than the gum. Among highly dependent smokers, those on the inhaler had a lower relapse rate than those on the other products. CONCLUSIONS: Regardless of initial preferences, whether patients obtain their preferred form of NRT or one selected for them did not seem to affect outcome. This may be because smokers came to like particular products as they got used to them. Other things being equal, women may be better advised to use inhaler rather than gum and men vice versa. PMID- 11205424 TI - Gender-related differences in response to placebo in benzodiazepine withdrawal: a single-blind pilot study. AB - RATIONALE: Benzodiazepines have dependency-producing properties, and the majority of patients who are prescribed benzodiazepines and are treated for benzodiazepine dependency are women. Inability to cope with withdrawal symptoms may lead to continued consumption of benzodiazepines, often with the development of tolerance and dose escalation as a consequence. OBJECTIVE: In the present study we analyzed gender-related differences in reactions to placebo injections in a placebo controlled study of the effects of the benzodiazepine antagonist flumazenil among patients previously treated for benzodiazepine dependency and healthy controls. METHODS: Ten patients and ten controls (five males and five females in each group) received two placebo injections (separated by 15 min) on two separate occasions (1-13 weeks apart). The patients had been benzodiazepine free for 47 (4 266) weeks on the first occasion. Subjective ratings of symptoms, thought to be important during/after withdrawal of benzodiazepines, were made before and after each injection, as well as registrations of blood pressure and heart rate. RESULTS: An overall difference existed between previously benzodiazepine dependent subjects and healthy controls, with patients scoring higher on negative and somatic aggregates and lower on a positive aggregate. A four-way interaction (group x gender x occasion x time) was found for negative and somatic aggregates, which could mainly be explained by the reactions of female patients. Thus, females had the highest base-line ratings and were the only group that showed a significant reduction in symptom ratings after placebo injections on the first occasion. Gender differences were also found for systolic and diastolic blood pressure. There was no significant response to placebo among male patients or for controls (males or females) for ratings of any variable. CONCLUSIONS: The results suggest that there might be gender-specific differences in reactions to placebo injections, with female patients being more affected. Arguments for and against explanatory factors such as expectation, provider factors, habituation, regression toward the mean, and reduction of anxiety are presented. PMID- 11205425 TI - Relationship between plasma risperidone and 9-hydroxyrisperidone concentrations and clinical response in patients with schizophrenia. AB - RATIONALE: Evaluation of relationships between serum antipsychotic drug concentrations and clinical response may provide valuable information for rational dosage adjustments. For risperidone, this relationship has been little investigated to date. OBJECTIVE: To assess the relationship between plasma concentrations of risperidone and its active 9-hydroxy-metabolite (9-OH risperidone) and clinical response in schizophrenic patients who experienced an acute exacerbation of the disorder. METHODS: Forty-two patients (30 males, 12 females, age 24-60 years) were given risperidone at dosages ranging from 4 to 9 mg/day for 6 weeks. The design of the study was open and risperidone dosage could be adjusted individually according to clinical response. Steady-state plasma concentrations of risperidone and its 9-hydroxymetabolite were measured after 4 and 6 weeks using a specific HPLC assay. Psychopathological state was assessed at baseline and at weeks 2, 4, and 6 by means of the positive and negative syndrome scale (PANSS), and patients were considered responders if they showed a greater than 20% reduction in total PANSS score at final evaluation compared with baseline. RESULTS: Mean plasma concentrations of risperidone, 9-OH-risperidone, and active moiety (sum of risperidone and 9-OH-risperidone concentrations) did not differ between responders (n = 28) and non-responders (n = 14). No correlation between plasma levels and percent decrease in total PANSS score was found for risperidone (rs = -0.187, NS), 9-OH-risperidone (rs = 0.246, NS), and active moiety (rs = 0.249, NS). Active moiety concentrations in plasma were higher (P < 0.001) in patients developing clinically significant parkinsonian symptoms (n = 7) than in those with minimal (n = 7) or no drug-induced parkinsonism (n = 28). CONCLUSIONS: In chronic schizophrenic patients experiencing an acute exacerbation of the disorder, plasma levels of risperidone and its active metabolite correlate with the occurrence of parkinsonian side effects, whereas no significant correlation appears to exist with the degree of clinical improvement. PMID- 11205426 TI - Three sets of diagnostic criteria for major depression and correlations with serotonin-induced platelet calcium mobilization in cancer patients. AB - OBJECTIVE: Enhanced serotonin-induced platelet calcium mobilization has been proposed to be a biological marker for the pathophysiology of major depression in physically healthy patients. To determine the most appropriate method of diagnosing major depression in cancer patients, we compared serotonin-induced platelet calcium mobilization between patients with and without major depression diagnosed according to three different sets of diagnostic criteria (inclusive, substitutive and exclusive). METHODS: Among the cancer patients referred to our institution between June 1997 and March 1998, 24 patients diagnosed as having major depression according to the inclusive approach (in which the nine traditional symptoms of major depression contribute towards the diagnosis of depression regardless of its presumed etiology) participated in the study. Serotonininduced platelet calcium mobilization was examined in these patients and in the same number of non-depressed controls matched for age, sex, cancer stage and cancer site. The depressed patients were then re-evaluated using substitutive and exclusive criteria, and calcium mobilization comparisons with the relevant controls were repeated. RESULTS: Compared with the controls, an enhanced serotonin-induced platelet calcium response was only observed in the patients with major depression according to the exclusive criteria. No significant enhancement was observed when the inclusive or substitutive approaches were used. CONCLUSION: These findings, based on the use of enhanced serotonin-induced platelet calcium mobilization as a biological marker, suggest that the exclusive approach might be the most valid and appropriate method of diagnosing major depression in cancer patients, while the inclusive and substitutive approaches might overestimate the occurrence of major depression in these patients. PMID- 11205427 TI - Effects of abstinence and smoking on information processing in adolescent smokers. AB - RATIONALE: Although adolescent smokers appear to display some of the hallmark features of dependence, the biological and behavioral effects of smoking in this population are poorly understood. OBJECTIVES: This study aimed to define empirically the effects of abstinence and smoking in adolescent smokers, using indices validated in adult smokers. METHODS: Subjects were 16 young novice smokers (five male, 11 female), ages 14-18 years. A modified Stroop task measured the ability to inhibit attention to smoking-related cues; the classic Stroop task measured the ability to inhibit a pre-potent response (i.e. reading a word); a rapid information processing (RIP) task measured vigilance. RESULTS: Abstinence increased and smoking decreased the intrusiveness of smoking cues. Parallel effects were seen in commission errors on the RIP task. These effects were restricted to heavier smokers (>11 cigarettes/day). Subjective withdrawal effects predicted the intrusiveness of smoking words during abstinence. The number of cigarettes smoked per day predicted the beneficial effect of smoking on the classic as well as modified Stroop tasks. The physiological effects of abstinence and smoking predicted RIP performance. CONCLUSIONS: Abstinence impairs and smoking improves inhibitory information processing in young novice smokers in a manner similar to adult smokers. Daily frequency of smoking is a critical moderator of these effects. PMID- 11205428 TI - Improved incidental memory with nicotine after semantic processing, but not after phonological processing. AB - RATIONALE: A number of lines of evidence suggest that a nicotinic cholinergic system is mediating attentional processing. However, the evidence is less clear for a nicotinic system being involved in mnemonic processing. OBJECTIVES: The present study investigated the effects of nicotine on memory using a depth of processing paradigm. METHODS: A double-blind design was used with participants (n = 40) smoking either a nicotine containing cigarette (n = 20) and a denicotinized cigarette (n = 20). After smoking, each set of these participants was further subdivided into two groups (n = 10 for each). One group were presented with a series of trials each beginning with the presentation of a "decision word" which they had to say whether it represented something which was living or non-living (semantic-orienting). The second group had to say whether the word had one syllable or two syllables (phonological or non-semantic orienting condition). This decision was followed by a word in coloured ink whose colour participants were required to name as quickly as possible. On completion of the whole task the participants were given an unexpected free recall test. RESULTS: The nicotine containing cigarette reduced the latencies for decision-making and colour naming in comparison with the denicotinized cigarette. The free recall test showed that nicotine-containing cigarette increased the number of words remembered, but only for the semantic-orienting condition and not the non-semantic condition. CONCLUSIONS: There is a nicotinic cholinergic system that mediates effortful processing. It can be deployed for attentional processing, including the associative processing required for memory encoding. PMID- 11205429 TI - Fluoxetine in the treatment of Huntington's disease. AB - RATIONALE: Recent reports suggest the possible efficacy of selective serotonin reuptake inhibitors (SSRIs) in treating particular symptoms of Huntington's disease (HD), such as aggressiveness and agitation. However, predictive features to identify HD subjects who may benefit from this treatment have not been established. OBJECTIVES: Two individuals from a large HD pedigree with a very high prevalence of obsessive-compulsive disorder (OCD) have been treated with fluoxetine, an SSRI. We aimed at testing whether the co-occurrence of the two disorders in this pedigree might have some underlying pathogenic similarities, maybe also resulting in a good response of HD symptoms to the anti-obsessional drug fluoxetine. METHODS: Each patient was evaluated, started on fluoxetine treatment, and then reassessed monthly with: (a) the HD motor rating scale, to rate the impairment of movement, and (b) the mini mental state examination, for a cognitive ascertainment. They had a complete psychiatric and neurologic examination as well. RESULTS: Both subjects showed an excellent response to fluoxetine. One patient exhibited improvement of the motor and behavioral components of the disorder, while the other improved also in the cognitive domain of HD. The best response was shown by the individual suffering from OCD in her youth. The amelioration in these two patients has been maintained for 2 and 6 years, respectively, whereas the course of HD is that of a progressive deterioration. CONCLUSIONS: Firm conclusions to explain these results cannot be drawn. However, a hypothetical involvement of the serotonergic system, suggested by the excess of OCD in the pedigree, seems supported by the response of these two individuals to fluoxetine. It may be worth further exploring the value of the psychiatric picture in selecting the appropriate treatment for at least some cases of HD. PMID- 11205430 TI - Synergistic efects of opioid and cannabinoid antagonists on food intake. AB - RATIONALE: Central cannabinoid systems have been implicated in appetite regulation through the hyperphagic effects of exogenous and endogenous cannabinoids. These effects may involve activation of reward systems and be mediated in part by opioidergic processes. OBJECTIVE: Cannabinoid-opioid interactions in feeding were examined by testing the combined effects on food intake of sub-anorectic doses of selective antagonists for CB1 and opioid receptors. METHODS: Male rats (n = 8) received subcutaneous injections of naloxone (0, 0.1, 0.5, 1.0 mg/kg) and SR141716 (0, 0.1, 0.5, 1.0 mg/kg) before l h, nocturnal food (chow) intake tests. RESULTS: Neither naloxone nor SR141716 reliably affected feeding when administered alone. By contrast, combined administration of the two antagonists significantly suppressed chow intake at each dose combination. Joint administration of the highest doses of each antagonist suppressed intake by 73%, a significantly greater effect than produced by either naloxone (32%) or SR141716 alone (17%). CONCLUSION: The data reveal a synergistic interaction between the effects of naloxone and SR141716 on feeding, provide further evidence of important functional relationships between endogenous cannabinoid and opioid systems, and strengthen the postulated role for endocannabinoids in reward processes contributing to the normal control of appetite. PMID- 11205432 TI - Kinetics of hydroxyapatite precipitation at pH 10 to 11. AB - The mechanism and kinetics of hydroxyapatite (HAP) precipitation from aqueous solution at the conditions of pH 10-11 and at calcium ion concentrations of more than 0.5 mol/l were investigated. The results show that the reaction undergoes the following process: transferring from octacalcium phosphate (OCP) to amorphous calcium phosphate (ACP) rapidly, and then from ACP to calcium-deficient hydroxyapatite (DAP) and HAP. DAP was the non-stoichiometric material that ACP converts to HAP. Reaction temperature greatly affects the reaction rate of the conversion from ACP to HAP. It takes about 24 h to form pure-phase HAP at 25 degrees C while it takes only 5 min at 60 degrees C. The temperature also has a great deal of influence on the particle size and morphology of precipitated hydroxyapatite. The reaction of transformation from ACP to DAP was second order and the activation energy was 95 kJ/mol (22.7 kCal/mol) and therefore it was inferred that the conversion reaction was a surface control process. PMID- 11205431 TI - Allelic variation in the 5-HT2C receptor (HT2RC) and the increase in slow wave sleep produced by olanzapine. PMID- 11205433 TI - Analysis of products diffused into UHMWPE prosthetic components in vivo. AB - Ten UHMWPE hip inserts, five ethylene oxide and five gamma-ray sterilised in air, were retrieved during surgical revision after aseptic failure. Time in situ varied from 6 to 23 years. First implant was carried out for degenerative arthritis in all cases. The retrieved inserts were cut into two parts perpendicular to the articulate surface and a series of 150 microm thick slices were obtained from the cross-section. These were studied by FTIR microscopy and the absorbed products were extracted with cyclohexane for identification by GC/MS and Py/GC/MS. All retrieved UHMWPE components, independent of the sterilisation method, showed species adsorbed on the surface, which were mainly synovial liquid protein components. In addition, species such as cholesterol, fatty esters of cholesterol and squalene, also originating from synovial liquid, were found in the bulk. The concentration of the different species varies depending on the individual patient. PMID- 11205434 TI - Cytotoxicity of dental composite components and mercury compounds in pulmonary cells. AB - The cytotoxic potentials of the dental composite components triethyleneglycoldimethacrylate (TEGDMA) and 2-hydroxy-ethylmethacrylate (HEMA) as well as mercuric chloride (HgCl2) and methyl mercury chloride (MeHgCl) were investigated. Proliferating A549 and L2 cell monolayers were cultured in the absence or presence of composite components or mercurials. Twenty-four hours later the tetrazolium salt XTT (sodium 3'-[1-phenyl-aminocarbonyl)-3,4 tetrazolium]bis(4-methoxy-6-nitro)benzenesulphonic acid) was added. Formazan formation was quantified using a microtiter plate reader. EC50 values were obtained as half-maximum-effect concentrations from fitted curves. EC50 values were in A549 cells (mean values +/- standard deviation; n = 12; micromol/l); HEMA 8854+/-1882; TEGDMA 1821+/-529; HgCl2 41+/-7 and MeHgCl 27+/-3. EC50 values in L2 cells were: HEMA 191+/-28; TEGDMA 112+/-16; HgCl2 25+/-6 and MeHgCl 8+/-6. All tested substances induced a dose-dependent loss of viability in A549 and L2 cells after 24 h. The EC50 values of both mercurials were significantly (p < 0.05) lower compared to the values of both composite components. TEGDMA was about 5 fold (A549 cells) and about 2-fold (L2 cells) more toxic compared to HEMA. It is to be assumed that the risk of lung cell damage by dental composite components is even more unlikely. PMID- 11205435 TI - A novel pH-sensitive membrane from chitosan--TEOS IPN; preparation and its drug permeation characteristics. AB - A novel organic-inorganic composite membrane was prepared, using tetra ethyl ortho silicate (TEOS) as an inorganic material and chitosan as an organic compound. Equilibrium and oscillatory swelling studies were conducted to investigate swelling behaviors of the membrane according to the pH of the swelling medium. Drug permeation experiments were also performed in phosphate buffer solution of the pH of 2.5 and 7.5, respectively. Lidocaine HCl, sodium salicylate and 4-acetamidophenol were selected as model drugs to examine the effect of ionic property of drug on the permeation behavior. The effects of membrane composition and the external pH on the swelling and the drug permeation behavior of IPN membrane could be summarized as follows; chitosan incorporated into TEOS IPN swelled at pH 2.5 while shrunk at pH 7.5. This swelling behavior was completely reversible and the membrane responded rapidly to the change in environmental pH condition. According to swelling behavior, an increase in pH from 2.5 to 7.5 yielded an increase in the rate of drug permeation because of the shrinking of the incorporated chitosan in TEOS IPN, while decrease in pH resulted in low permeation rate. The optimal TEOS-chitosan ratio for maximum pH sensitivity existed and drug permeation was influenced not only with the external pH but also with the ionic interactions between the drug and membrane. PMID- 11205436 TI - A preliminary in vitro study on the fabrication and tissue engineering applications of a novel chitosan bilayer material as a scaffold of human neofetal dermal fibroblasts. AB - The bilayer structure of chitosan film and sponge was designed as a scaffold of skin tissue engineering and a dermis substitute. It was processed successively via the formation of a dense chitosan film by casting method and a porous chitosan sponge by lyophilization. The dry thickness of the film layer was 19.6 microm and that of the sponge layer was controlled at 60-80 microm. Porogens such as sodium chloride, glucose, and sucrose were used to create large pores of the chitosan sponge layer. Human neofetal dermal fibroblasts were seeded in the chitosan sponge layer and cultured for 4 weeks. It was found that the cells could grow and proliferate well in an extended shape on the flat bottom of large pores with 15-100 microm width and in spherical form on the rough pore walls or at the edges of micropores less than 5 microm. Fibroblasts after the culture could bind tightly with the sponge layer via newly formed extracellular matrices to give a living cell-matrix-chitosan composite. The bilayer chitosan material remained stable in shape and size during the cell culture. The results suggested that the bilayer chitosan material would be an alternative of collagen materials which was obviously contracted during cell culture. PMID- 11205437 TI - Osteoblast growth on titanium foils coated with hydroxyapatite by pulsed laser ablation. AB - Pulsed laser ablation is a new method for deposition of thin layers of hydroxyapatite (HA) on to biomaterial surfaces. In this paper, we report activity and morphology of osteoblasts grown on HA surfaces fabricated using different laser conditions. Two sets of films were deposited from dense HA targets, at three different laser fluences: 3, 6 and 9 Jcm(-2). One set of the surfaces was annealed at 575 degrees C to increase the crystallinity of the deposited films. Primary human osteoblasts were seeded onto the material surfaces and cytoskeletal actin organisation was examined using confocal laser scanning microscopy. The annealed surfaces supported greater cell attachment and more defined cytoskeletal actin organisation. Cell activity, measured using the alamar Blue assay, was also found to be significantly higher on the annealed samples. In addition, our results show distinct trends that correlate with the laser fluence used for deposition. The cell activity increases with increasing fluence. This pattern was repeated for alkaline phosphatase production by the cells. Differences in cell spreading were apparent which were correlated with the fluence used to deposit the HA. The optimum surface for initial attachment and spreading of osteoblasts was one of the HA films deposited using 9 J cm(-2) laser fluence and subsequently annealed at 575 degrees C. PMID- 11205438 TI - Coagulation and complement activation. AB - The purpose of this investigation was to assess the effect of heparin coating of a new stent construction (Stent Graft, Jomed Implantate GmbH, Germany) on platelet and coagulation activity. METHODS: Stent grafts with an ePTFE membrane interfoliated between two stents were deployed in tubings to form Chandler loops. Fresh human blood with a low concentration of heparin was rotated for 1 h, then collected and used for measurements of platelet number, thrombin-antithrombin complex (TAT), CD11b, C3a and C5b-9. There were five study groups: Group 1, conventional unmodified stents (n = 8); Group 2, untreated stent grafts (n = 8); Group 3, heparin-coated stents and untreated membrane (n = 7); Group 4, heparin coated stents and membrane (n = 8); Group 5, heparin-coated PVC tubings with no stents (n = 8). RESULTS: There was a significant drop in platelet count, increase in TAT-values and CD11b expression in Groups 1-3 but not in Group 4 compared to Group 5. Examination by scanning electron microscopy revealed extensive activation on non-modified stents but almost no deposition of thrombotic material on heparin-modified stent grafts. CONCLUSIONS: With unmodified stents and membrane there were signs of significant activation of platelets and coagulation. In contrast, the heparin-coated stent graft induced much less alterations, indicating improved blood compatibility. PMID- 11205439 TI - In vivo comparison of bioactive glass particles in rabbits. AB - Bioglass particles of the compositions 45s5, 52s and 55s were implanted in the distal femoral epiphysis of rabbits. Animals were sacrificed at 7, 28, and 84 d postoperatively and specimens investigated using light microscopy and histomorphometry. Bone bonding occurred in a zentripetal fashion and fastest for 45s5. Bone formation was hampered at the core of the implantation bed where bone bonding showed a peak at 28d and diminished at 84d (except for 55s). This went along with a significant increase in numerous multinuclear giant cells (MNGC). Implantation model, particle size and surface-area-to-volume ratio are discussed as possible parameters determining bone regeneration. PMID- 11205440 TI - Protein release from physically crosslinked hydrogels of the PLA/PEO/PLA triblock copolymer-type. AB - A series of PLA/PEO/PLA triblock copolymers was prepared by ring opening polymerization of rac-lactide in the presence of various di-hydroxyl poly (ethylene glycol)s, using CaH2 as a biocompatible initiator. Hydrogels were prepared by a phase separation method consisting of introducing small amounts of water over solutions of the copolymers in a biocompatible organic solvent, namely tetraglycol [poly(ethylene glycol monotetrahydrofurfuryl ether)]. The resulting hydrogels appeared much more hydrophilic than the rather tough hydrogels formed by swelling of dry tablets or films processed from the same copolymers. The phase separation-derived hydrogels were soft enough to be injected through a trochar. Two proteins, namely bovine serum albumine (BSA) and fibrinogen, were physically entrapped in these hydrogels by mixing with the polymer solutions before gel formation. This procedure appeared to be protein-respecting according to circular dichroism analysis on the released BSA. Dramatically different release profiles were obtained for the two proteins. In the case of BSA, the release depended on the quantity of protein incorporated in the hydrogel and presented a parabolic type profile, in agreement with the behaviors of diffusion-controlled monolitic drug delivery devices. In contrast, almost linear release profiles were observed in the case of fibrinogen, the hydrogels behaving like a reservoir drug delivery system. These findings are tentatively interpreted in terms of gel-protein compatibility in the case of BSA and gel-protein incompatibility in the case of fibrinogen. PMID- 11205441 TI - Properties of crosslinked ultra-high-molecular-weight polyethylene. AB - Substantially reducing the rate of generation of wear particles at the surfaces of ultra-high-molecular-weight polyethylene (UHMWPE) orthopedic implant bearing components, in vivo, is widely regarded as one of the most formidable challenges in modern arthroplasty. In the light of this, much research attention has been paid to the myriad of endogenous and exogenous factors that have been postulated to affect this wear rate, one such factor being the polymer itself. In recent years, there has been a resurgence of interest in crosslinking the polymer as a way of improving its properties that are considered relevant to its use for fabricating bearing components. Such properties include wear resistance, fatigue life, and fatigue crack propagation rate. Although a large volume of literature exists on the topic on the impact of crosslinking on the properties of UHMWPE, no critical appraisal of this literature has been published. This is one of the goals of the present article, which emphasizes three aspects. The first is the trade-off between improvement in wear resistance and depreciation in other mechanical and physical properties. The second aspect is the presentation of a method of estimating the optimal value of a crosslinking process variable (such as dose in radiation-induced crosslinking) that takes into account this trade off. The third aspect is the description of a collection of under- and unexplored research areas in the field of crosslinked UHMWPE, such as the role of starting resin on the properties of the crosslinked polymer, and the in vitro evaluation of the wear rate of crosslinked tibial inserts and other bearing components that, in vivo, are subjected to nearly unidirectional motion. PMID- 11205442 TI - Child speech and language assessment and measurement. AB - The necessity of using standardized and norm-referenced tests in assessing speech and language of impaired children has now been recognized. Thus it seems useful to summarize based on the literature principles for founding such testing methods. These include: a) the necessity for a neuropsycholinguistic model that allows the speech-language pathologist to relate the observed linguistic behavior to underlying language processes, b) the knowledge of the psychometric characteristics required for language tests, and c) a discussion of some of the difficulties or controversed points from clinical practice. Among these latter the following are discussed: 1) measurement versus clinical observation, 2) screening versus exhaustive assessment, 3) language linguistic aspects versus pragmatic dimension, 4) formal tasks versus spontaneous language analysis, 5) linguistic versus metalinguistic assessment, 6) "knowledge-dependent" versus "processing-dependent" tests, 7) early detection of at risk children versus diagnosis of developmental language disorders. Diagnosticians are advised to be aware of the principles to respect when assessing child language. PMID- 11205443 TI - Cleft palate speech. AB - Cleft palate is a known pathology but there exists a lot of controversy about the therapy. The aim of this paper is to give a brief overview of the pathology itself and its consequences particularly in speech. At this point the velar and velopharyngeal function are stressed. PMID- 11205444 TI - Congenital CMV-infection and hearing loss. AB - CMV (cytomegalovirus) is one of the Herpesviridae, known for their potential for latency and reactivation. The sequelae of fetal infection are diverse: chronic stage of early fetal infection with brain anomalies, symptomatic late fetal infection with hepatitis and thrombocytopenia and asymptomatic infection. With any of these clinical phenotypes, permanent hearing loss is possible. CMV infection is the only relevant viral cause of perinatal hearing loss because rubella, measles and mumps have become rare due to vaccination. Recent studies have suggested beneficial effects on outcome of i.v. ganciclovir treatment in symptomatic cases. We have recently taken the challenge of treating asymptomatic newborns on the basis of active sonographic brain lesions in order to prevent labyrinth destruction. We would also like to stress the importance of suspecting children with congenital hearing loss, or hearing loss that develops in the first year of life, of having an asymptomatic congenital CMV-infection. Follow up in the first years of life is necessary in these children because further progression of hearing loss is possible. PMID- 11205445 TI - Results of cerebellopontine space imaging by magnetic resonance during one year. AB - The authors present the results of a retrospective study concerning 231 magnetic resonance imaging (MRI) of the cerellopontine space requested by the otologists of the department between September 1996 and September 1997. The motives of imaging were sensorineural hearing loss (44%), vertigo and unsteadiness (25.5%), tinnitus (16.5%) and other (13%). The MRI was abnormal in 18% of the cases and the diagnosis of acoustic schwannoma was made in 10% of the cases. PMID- 11205446 TI - What future in the 21st century for tibial bone allografts in ossicular chain reconstruction: the state of the issue. AB - After using tibial cortical bone allografts in reconstructing the middle ear over a period of ten years, the authors analyze their results. They compare the functional and anatomical outcome at 4 years of 24 patients who received this allografts with a series of 25 patients who underwent incus transposition. Results were analyzed in two different ways: the Air Bone Gap and the Glasgow Benefit Plot. The discussion addresses the techniques used to reduce risks of iatrogenic transmission of viruses and prions, the current legislation in Belgium and the comparative costs, after refunding of the various reconstruction materials. The authors conclude that, because the present-day preparation techniques offer a certain security with regard to transmission risks and because of its numerous advantages (mechanical properties, tolerance, cost and availability), tibial cortical bone still has a promising future. PMID- 11205447 TI - Effectiveness of a structured questionnaire for diagnosis of Meniere's disease in the first visit. AB - A structured questionnaire of vertigo (SQV) was used to search patients with Meniere's disease (MD) in the first visit. One-hundred consecutive outpatients that complained of dizziness or vertigo were studied. Diagnosis of MD was accepted if three investigators independently recorded it among a list of 29 diagnostic categories after reviewing the SQV. The AAO criteria for definite MD defined by the Committee on Hearing and Equilibrium after 10 months or more of follow-up were the gold standard to contrast questionnaire-based diagnosis. Seven patients were considered as MD with the SQV. The sensitivity (Sn), specificity (Sp) and positive predictive value of the SQV for definite MD were 80%, 97% and 57% respectively, being the false positive rate 3%. The probability for diagnosis of definite MD using the SQV in the first visit was 58% in a set up with a 5% of prevalence. The best predictor selected by all investigators was the presence of hearing loss (Sn 100%, Sp 85%, positive likelihood ratio 6.67). Because of the high specificity, the SQV of vertigo results a useful test to advance the diagnosis of definite MD. PMID- 11205448 TI - Clinical advantage of abscess tonsillectomy in peritonsillar abscess. AB - At the moment, regardless of the prevalence of the peritonsillar abscess (PTA), a definite protocol concerning the treatment of PTA has not yet been established and the treatment remains controversial. In the treatment of PTA the two most used therapeutic approaches are compared in this short study carried out on 16 patients. A group of patients presenting PTA received an abscess tonsillectomy (AT) is compared with another group treated with aspiration and subsequently operated on with interval tonsillectomy (IT). The results show obviously that the abscess tonsillectomy is better than the interval tonsillectomy in every aspect of treatment. The hospitalization time and global costs are also reduced. So when a young person has PTA and once the indication of tonsillectomy is posed, the operation has to be carried out "a chaud". PMID- 11205449 TI - Intradermal tests with vasomotor agents in perennial non-allergic rhinitis. AB - Nasal reactivity in non-allergic rhinitis patients is well known, but the skin reactivity of these patients is less examined. The aim of this prospective study was to examine the skin reactivity to four vasomotor agents in healthy subjects and perennial non-allergic rhinitis patients and to determine whether rhinitis patients differ from healthy subjects or not. Seventy four perennial non-allergic rhinitis patients and fourty two healthy subjects were undergone to intradermal testing with papaverine (5 mg/ml), metacholine (0.02, 0.2 and 2.0 mg/ml), histamine (0.01, 0.1 and 10.0 micrograms/ml) and compound 48/80 (0.01, 0.1, 1.0 and 10.0 micrograms/ml). It was found that the frequency of pathological skin reactivity to papaverine in perennial non-allergic rhinitis patients (34%) was significantly greater (p = 0.007) then in healthy subjects (9.5%). There was no significant difference for metacholine, histamine, compound 48/80 and saline between these two groups. The frequency of the total pathological skin reactivity to vasomotor agents, singly and in combinations, in perennial non-allergic rhinitis patients (80%) was significantly greater (p = 1.8.10(-6)) then in healthy subjects (33%). These findings suggest that the pathological skin reactivity to vasomotor agents is a feature of perennial non-allergic rhinitis patients as well as healthy subjects and indicate that a difference in the skin reactivity between these groups is noticed. PMID- 11205450 TI - The antrochoanal polyp. AB - The antrochoanal polyp is a particular pathology of nasal fossae and sinuses. Since the first description made by Killian, several pathogenic mechanisms and surgical techniques have been reported. The polyp exeresis is classically made using the Caldwell-Luc approach. The aim of our study is to lay stress on the interest of endonasal surgery compared to other surgical procedures. Between 1996 and 1998, we operated on 12 cases by endonasal approach. Diagnosis is made upon clinical, CT-scan and pathological data. In all cases, an extended middle meatotomy is performed. In 3 cases, it is associated with an inferior meatotomy. The polyp pedicle is systematically coagulated at level of its maxillary implantation area. No recurrence, nor operative complication are noted. The average follow-up is 12 months. PMID- 11205451 TI - Testicular tumor metastatic to the nose. A case report. AB - In this paper we present an uncommon tumor found in the nasal cavity, the result of a metastasis from primary tumor of testis (embryonal carcinoma) in a young patient of 24 years of age. For this uncommon tumor we discuss the case with the Greek and foreign bibliography. PMID- 11205452 TI - Aneurysmal bone cyst of the zygoma. A case report and review of the literature. AB - Aneurysmal bone cyst is a cystic vascular osseous tumor. It is rare in the craniofacial area; it is even rarer in the zygoma. A case of aneurysmal bone cyst of the zygoma was presented. Its pathogenesis, clinical and radiological features and treatment options were discussed under the view of the literature. PMID- 11205453 TI - Upper airways locations of plasmocytoma. AB - We report one case of extramedullary plasmocytoma located in the nasopharynx. After 8 years, the tumor recurred in the same location and 3 years later, the patient develop a multiple myeloma. Three clinical and pathological entities of plasmocytoma are described: multiple myeloma, solitary bone plasmocytoma and extramedullary plasmocytoma. When histological examination show plasmocytoma, further examinations can or not reveal a multiple myeloma. In 80% of cases, extramedullary plasmocytoma occur in the upper respiratory tract. This development of multiple myeloma from extramedullary plasmocytoma is seen in 5 to 32% of patients and sometimes an extremely long time is required for the change to occur. The treatments are surgery and radiation in the absence of generalized disease. PMID- 11205454 TI - Cervical lymphadenitis and cat scratch disease (CSD): an overlooked disease? AB - Cat Scratch Disease (CSD) is a benign disease characterized by regional lymphadenopathy affecting most frequently the head and neck region in children and young adults. In the present paper, the authors describe four cases of CSD focusing on clinical history, diagnostic management and therapy. The main germ responsible for this lymph node disease is Bartonella henselae. Diagnosis is based on history, serology and histological findings. Clinical evolution is generally favorable despite the fact that complications occur in about 5% to 13% of patients including encephalitis, hepatitis and Parinaud's oculoglandular syndrome. Antibiotic treatment is only considered for highly symptomatic patients. Surgical excision of the lymphadenopathy is useful to establish the diagnosis when serology is not available and/or when the adenopathy become fluctuating. The authors emphasize the increasing incidence of patients with CSD in the ENT population and the algorithm for CSD disease affecting the cervical lymph nodes. PMID- 11205455 TI - A national cancer plan for the UK. PMID- 11205456 TI - Assessing the quality of economic evaluations of health care interventions. PMID- 11205457 TI - Predictors of outcome in cancer patients with candidemia. AB - BACKGROUND: Hematogenous candidiasis is associated with a substantial mortality and morbidity in critically ill patients. Candidemia is the best marker for hematogenous infection; therefore, most studies have examined the outcome of candidemia. However, few have focused on the predictors of outcome in cancer patients with candidemia. MATERIALS AND METHODS: We conducted a MEDLINE search for all study reports published from 1974 to 1999 on candidemia and prognostic factors including predictors of mortality. Ten articles that provided sufficient data were evaluated in detail. RESULTS: The overall mortality rate was reported to be 33%-75%. Univariate analyses identified severity of underlying disease, performance status, neutropenia, Candida species, source of candidemia and the extent of visceral involvement as important prognostic variables. In multivariate analyses, however, only host factors and extent of infection (rather than infecting Candida species) were predictive of mortality. CONCLUSIONS: Older age, poor performance status, presence and persistence of neutropenia, and extensive organ involvement with candidiasis are the most important prognostic factors for candidemia in cancer patients. PMID- 11205458 TI - Chemotherapy in advanced androgen-independent prostate cancer 1990-1999: a decade of progress? AB - BACKGROUND AND PURPOSE: A great number of clinical research studies have been reported in the field of chemotherapy for advanced androgen-independent prostate cancer during the last ten years. The aims of the present review were to assess their impact on management of the disease and on survival of patients. METHODS: The review of full published reports was facilited by the use of a MEDLINE computer search. RESULTS: Clinical research studies have focused on defining guidelines for eligibility criteria and accurate endpoints for patients to be enrolled onto clinical trials and developing new agents or combination of drugs including estramustine phosphate. Any combination of current chemotherapy has no impact on overall survival of patients. Among drugs in development, only the promising activity observed with docetaxel deserves randomized trials to assess its impact on survival. The major innovative advance of the 90s is the demonstration of the impact of chemotherapy (mitoxantrone + prednisone) on quality of life as compared to prednisone alone. A greater and longer-lasting improvement in quality of life along with a concomitant decrease in costs was observed. CONCLUSIONS: At the present time, chemotherapy should be considered as a palliative treatment in patients with symptomatic androgen-independent disease. The enrollment of patients into clinical trials dealing with quality of life as primary endpoint is strongly solicited. A standard methodology should be used in phase II trials with a primary goal of selection of agents which should progress to randomized trials using survival as an endpoint. Hopefully new specific strategies targeted to reverse the molecular changes that underlie prostate tumorigenesis should rapidly impact the multimodality management of AIPC in the third millenium. PMID- 11205459 TI - A phase II trial of docetaxel in platinum pre-treated patients with advanced epithelial ovarian cancer: a Japanese cooperative study. AB - BACKGROUND: This phase II study was conducted to evaluate the efficacy and toxicity of docetaxel in Japanese patients with advanced ovarian cancer. PATIENTS AND METHODS: Docetaxel was administered at a dose of 70 mg/m2 intravenously to patients with platinum pretreated advanced ovarian cancer. Treatment was repeated every three weeks. No routine corticosteroid premedication was given. RESULTS: Ninety patients with advanced ovarian cancer were entered and sixty were assessable for response. The overall response rate was 28% in the assessable patients (95% confidence interval (95% CI): 17.54%-41.4%). CA125 responses were seen in 8 (24%) of 34 assessable patients for CA125 criteria. The 36 platinum refractory patients had a response rate of 25% compared with 33% in the platinum sensitive patients. The predominant toxicity was neutropenia, with 86% of the patients experiencing grade 3 or 4. Hypersensitivity reactions occurred in 37% of the patients and were not life threatening. Edema was mild and infrequent. CONCLUSION: Docetaxel at 70 mg/m2 demonstrated effectiveness as a treatment of both platinum-sensitive and platinum-refractory ovarian cancer patients, with a low incidence of severe hypersensitivity reactions and edema. PMID- 11205460 TI - Second cancers after adjuvant tamoxifen therapy for breast cancer in Japan. AB - BACKGROUND: Women treated with tamoxifen for breast cancer are at increased risk of endometrial cancer. We conducted a retrospective cohort study to evaluate the risk of second primary cancers after adjuvant tamoxifen therapy for breast cancer in Japan. PATIENTS AND METHODS: The subjects of the study were 6148 women who had been diagnosed with stage I, II, or IIIA unilateral primary breast cancer and had received surgical treatment during the period from January 1982 through December 1990 at nine institutions in Japan. The information on each patient was obtained from medical records or a prospectively compiled computer database at each institution. RESULTS: Of the 6148 women, 3588 (58.4%) were administered tamoxifen as an adjuvant treatment and 2560 (41.6%) were not administered. Median follow-up periods were 7.64 years for tamoxifen-treated patients and 8.10 years for non tamoxifen-treated patients, respectively. The duration of tamoxifen treatment was mostly two years or less (80.7%), and few patients received tamoxifen for more than five years. The cumulative incidence rates of all second cancers at 10 years were 4.61% and 4.09% among tamoxifen-treated and non-tamoxifen-treated patients (P = 0.62), respectively, and the incidence rate ratio (IRR) for all second cancers was 1.06 (95% confidence interval (CI): 0.77-1.47) after adjustment of several covariates. The numbers of endometrial cancers was 9 and 3 among tamoxifen-treated and non-tamoxifen-treated patients, respectively, and the IRR was 2.37 (95% CI: 0.64-8.77, P = 0.20). Of the 12 patients who developed endometrial cancer, 4 died of cancer (for 3 of them, the cause of death was breast cancer), and the other 8 patients were alive as of March 1996. Stomach cancer was the most frequent second cancer and the IRR was 1.34 (95% CI: 0.76 2.38, P = 0.31). There was no substantial increase in any other type of gastrointestinal cancer such as colorectal and liver cancers among tamoxifen treated patients. CONCLUSIONS: The incidence and risk of second primary cancers associated with tamoxifen therapy is low. The potential benefit of adjuvant tamoxifen therapy in breast cancer patients outweighs the risk of second primary cancers for Japanese breast cancer patients. PMID- 11205461 TI - ErbB2 status and the benefit from two or five years of adjuvant tamoxifen in postmenopausal early stage breast cancer. AB - AIM: We aimed to study the importance of erbB2 status in early stage postmenopausal breast cancer for patients who participated in a trial of five vs. two years of adjuvant tamoxifen. PATIENTS AND METHODS: We analysed the erbB2 status of the tumours from 577 patients participating in the trial, either by a DNA amplification assay (n = 181) or by measurement of the protein level with flow cytometry (n = 396). RESULTS: ErbB2 was overexpressed or gene amplified in 102 of the patients (18%). Overall, erbB2-positive patients had a significantly lower recurrence-free probability than others, 62% at five years as compared to 83%, and showed a significantly decreased breast cancer survival rate (P = 0.0007). ErbB2 status was significantly associated with recurrence and death in Cox multivariate analysis, adjusting for nodal status, tumour size and estrogen receptor status. The relative risk of recurrence (RR) for five vs. two years of tamoxifen was analysed in relation to erbB2 status for patients still disease free two years after surgery. Whereas erbB2-negative patients showed significant benefit from prolonged treatment (RR = 0.62, 95% confidence interval (95% CI): 0.42-0.93), no benefit was evident for erbB2-positive patients (RR = 1.1, 95% CI: 0.41-3.2). When the same analysis was restricted to ER-positive patients a similar difference in relative hazard was obtained but the difference was not strictly significant (P = 0.065). CONCLUSIONS: For early stage breast cancer patients treated with adjuvant tamoxifen, overexpression of erbB2 is an independent marker of poor prognosis. The results suggest that overexpression decreases the benefit from prolonged tamoxifen treatment. PMID- 11205463 TI - Infusional ECarboF in patients with advanced breast cancer: a very active and well-tolerated out-patient regimen. AB - We performed a trial using the combination of epirubicin 50 mg/m2/day 1, carboplatinum AUC 5/day 1 and continuous 5-fluorouracil (5-FU) 200 mg/m2/day (every 4 weeks for 6 months) to confirm the efficacy and low toxicity profile of this regimen in breast cancer. In 51 patients with metastatic (n = 33) or locally advanced (n = 18) breast cancer the overall response rate was 86% (95% confidence interval (95% CI): 73%-94%): 94% in locally advanced and 81% metastatic disease. Grade 3-4 toxicity was low: 4% of patients presented with febrile neutropenia, 16% with severe palmar-plantar syndrome, 10% with Port-a-cath thrombosis. This study confirms the high efficacy of infusional 5-FU-based regimens and justifies further research into novel promising oral 5-FU derivatives. PMID- 11205462 TI - Follicular large cell lymphoma: long-term follow-up of 62 patients treated between 1973-1981. AB - PURPOSE: Investigators disagree on whether follicular large cell lymphoma (FLCL) behaves like other follicular lymphomas, with no plateau in the survival curve, or as a more aggressive but potentially curable lymphoma. We reported in 1984 results for 62 FLCL patients treated at our institution; the current report updates those results. PATIENTS AND METHODS: Sixty-two patients referred from 1973-1981, including fifteen (24%) patients with Ann Arbor stage I-II and forty seven (76%) with stage III-IV FLCL. Seven patients received radiation (XRT) alone, forty patients XRT and chemotherapy, and fifteen patients received chemotherapy alone. RESULTS: The median follow-up was 14.7 years. The median survival was 5.1 years, with 21% alive at 15 years. The failure-free survival (FFS) at 10 years was 31%. Univariate analysis revealed that age, Ann Arbor stage, and the International Index correlated with survival. Performance status, number of platelets, and LDH correlated with failure-free survival. CONCLUSIONS: FLCL responds to doxorubicin-based regimens similarly to diffuse large cell lymphoma. Patients with FLCL have the potential for prolonged failure-free survival. Variables that predict the survival in aggressive lymphomas apply as well in this type of lymphoma. PMID- 11205464 TI - Hepatic arterial 5-fluorouracil in patients with liver metastases of colorectal cancer: single-centre experience in 145 patients. AB - BACKGROUND: Hepatic arterial chemotherapy for liver metastases of colorectal cancer is still under discussion. Mainly because of the technical complications of this mode of treatment and the lack of a survival benefit in randomized studies. We performed an analysis of hepatic arterial 5-fluorouracil (5-FU) chemotherapy in 145 consecutive patients treated at a single institution. PATIENTS AND METHODS: One hundred forty-five patients with inoperable liver metastases from colorectal cancer were included. 5-FU, 1000 mg/m2/day continuous infusion for five days every three weeks, was delivered in the hepatic artery by percutaneous catheter or arterial access device. RESULTS: The response rate was 34% for all patients, 40% in patients with extrahepatic disease, and 15% in patients with i.v. 5-FU-based pretreatment. TTP and OS for all patients were 7.5 and 14.3 months, respectively. In patients with extrahepatic disease or i.v. 5-FU based pretreatment, OS was significantly shorter compared to patients without extrahepatic disease or 5-FU-based pretreatment (9.7 vs. 19.3 months and 10.1 vs. 17.4 months, respectively), forty-seven percent of patients stopped treatment because of a complication. Complications most often seen in patients with arterial ports were hepatic artery thrombosis (48%) and dislocation of the catheter (22%). CONCLUSIONS: The results of our analysis are in line with previous phase III studies. Extrahepatic disease and i.v. 5-FU-based pretreatment were prognostic for reduced OS. The complication rate of hepatic arterial delivery was worrisome. although, no negative impact on survival could be established. There is a strong need for improvement of hepatic arterial delivery methods before further evaluation of hepatic arterial PMID- 11205465 TI - Autoimmune hemolytic anemia in patients with non-Hodgkin's lymphoma: characteristics and significance. AB - BACKGROUND: The occurrence of autoimmune hemolytic anemia (AIHA) in patients with non-Hodgkin's lymphoma (NHL) is well known. However, there is lack of information in the literature in terms of the significance and impact of such phenomenon on the clinical course of these patients. PATIENTS AND METHODS: We analyzed the clinical and laboratory features, course and response of 16 patients with non Hodgkin's lymphoma (NHL) and autoimmune hemolytic anemia (AIHA). Patients with small lymphocytic lymphoma and angioimmunoblastic lymphadenopathy with dysproteinemia were excluded from the analysis. The significance of certain parameters, such as cell type (B- vs. T-cell), stage of NHL and presence of serum monoclonal immunoglobulin were examined. The cohort consisted of 501 patients with NHL evaluated during the study period. RESULTS: The response rate for the group of patients with NHL/AIHA and for the cohort was 44% and 62%, respectively; P = 0.0138. T-cell histology was overrepresented in the patients with AIHA/NHL (33% vs. 14%; P = 0.048). The occurrence of AIHA was not statistically significant among the four stages of NHL (P = 0.722), while a significantly higher proportion of patients with AIHA had serum monoclonol gammopathy when compared to the cohort (25% vs. 8%; P = 0.03). The patients with NHL who did not develop AIHA had better overall survival and median survival compared to the NHL/AIHA group (P = 0.006 and P = 0.0001, respectively). CONCLUSIONS: The study provides for the first time a descriptive clinicopathologic analysis of patients with AIHA and NHL. Certain pathologic and laboratory features were more likely to be associated with the occurrence of AIHA in patients with NHL. Most importantly, was the adverse impact of AIHA on the survival of patients with NHL. Therefore, this finding should be taken in consideration when risk-stratifying patients with NHL. PMID- 11205466 TI - A phase I dose escalation study of the matrix metalloproteinase inhibitor BAY 12 9566 administered orally in patients with advanced solid tumours. AB - BACKGROUND: This phase I study was performed to evaluate the safety, tolerability, and efficacy of the oral matrix metalloproteinase inhibitor BAY 12 9566 in patients with advanced solid tumours, and to identify the maximum tolerated dose and dose for use in subsequent studies. PATIENTS AND METHODS: BAY 12-9566 was administered to 29 patients at doses ranging from 100 mg o.d. to 1600 mg (given either 400 mg q.i.d. or 800 mg b.i.d.). Blood samples for pharmacokinetic analyses were drawn on days 1-5, day 15 and days 29 and 30. Patients were continued on daily oral treatment of BAY 12-9566 until a dose limiting toxicity or tumour progression occurred. RESULTS: A maximum tolerated dose was not defined because plasma levels of BAY 12-9566 could not be sufficiently increased, even with escalating doses of drug. Pharmacokinetic analysis suggested that absorption was saturable at higher doses. The predominant toxicities related to drug were asymptomatic reversible effects on platelets and transaminases and mild anemia. There were no significant musculoskeletal toxicities. No objective responses were seen at the doses tested, but stable disease was observed in some patients based on tumour measurements. CONCLUSIONS: The recommended dose of BAY 12-9566 for further studies is 800 mg b.i.d. as this dose provides maximal plasma levels that can be achieved with a convenient dosing schedule for a chronically administered oral agent. PMID- 11205467 TI - High-dose therapy with autologous stem-cell transplantation (ASCT) after first progression prolonged survival of follicular lymphoma patients included in the prospective GELF 86 protocol. AB - BACKGROUND: Among the 566 patients with follicular lymphomas (FL) included in the GELF 86 prospective trials from October 1986 to September 1995, 372 with progressive/relapsing disease were analyzed retrospectively to identify prognostic factors at first relapse. PATIENTS AND METHODS: For progressive FL, patients received mono- (22%) or polychemotherapy (78%) followed by high-dose therapy (HDT) with ASCT for 83 patients (22%). The median time to progression from initial treatment was 23 months (range 3-102 months) and 24% of documented patients (52 of 217) had histological transformation (HT). Salvage therapy produced an overall response in 64% of patients and the five-year survival from progression was 42%. RESULTS: For patients who underwent HDT with ASCT compared to standard treatment, five-year freedom from second failure was at 42% vs. 16% (P = 0.0001) and five-year survival was 58% vs. 38% (P = 0.0005), respectively. The benefit of HDT and ASCT remained if we consider only patients less than 65 years (five-year survival at 60% vs. 40%; P = 0.001). Multivariate analysis of parameters significant according to univariate analysis found that no ASCT at first progression, age at relapse > 50 years, progression on-therapy were adversely significant on survival. CONCLUSIONS: HDTwith ASCT compared to standard treatment prolonged remission and survival after first progression of FL patients. PMID- 11205468 TI - Reporting and dissemination of industry versus non-profit sponsored economic analyses of six novel drugs used in oncology. AB - PURPOSE: Our prior study found that pharmaceutical-sponsored and non-profit sponsored analyses differed in their published assessments of the economic value of six new oncology drugs. In this study, we expand on our earlier findings and evaluate the association between funding source and 1) characteristics of the published study report and 2) journal type for dissemination of the previously evaluated economic studies. METHODS: We reviewed the published cost-effectiveness literature for hematopoietic colony stimulating factors, 5-HT3 antagonist antiemetics. and taxanes. Two blinded investigators rated specific aspects of study reporting based on the US Public Health Service Panel on Cost-effectiveness in Health and Medicine criteria. Dissemination strategies were evaluated using impact factor scores from the Science Citation Index. RESULTS: The operational aspects of pharmaceutical-sponsored study reporting were better overall than those associated with non-profit sponsored studies. Specifically, pharmaceutical sponsored studies were more likely to be reported based on data obtained from randomized clinical trials or detailed cost-models (90% vs. 70%), to include descriptions of the source of cost differences (90% vs. 79%), to state whether the study was carried out from a societal, governmental, or insurer perspective (70% vs. 42%), and to clearly indicate the time-period over which costs were evaluated (65% vs. 50%). Nonprofit sponsored studies were more likely than pharmaceutical sponsored studies to report the generalizability of the findings, including being more likely to include information about how the data could be extrapolated to other clinical settings (58% vs. 35%), to include statements on the statistical significance of the findings (38% vs. 20%), and to clearly outline the cost per unit and data sources for the cost analyses (67% vs. 45%). A similar percent of pharmaceutical and non-profit sponsored studies reported background and conclusions with about 80% providing literature comparisons of the results (about 80%) and two thirds to three fourths discussing the limitations of the finding (75% for pharmaceutical-sponsored and 67% for non-profit sponsored studies). Most studies were published in low impact factor peer-reviewed journals, and journal impact factor scores were similar between pharmaceutical and nonprofit sponsored studies. CONCLUSIONS: Upon reviewing the entire pharmacoeconomic literature for six new oncology drugs, we identified differences in study reporting, but not in types of journals where studies were published, between pharmaceutical-sponsored and non-profit sponsored studies. These results, particularly the observed differences in data generalizability, may account in part for our previous finding of lower likelihood of reporting unfavorable conclusions in pharmaceutical-sponsored studies. PMID- 11205469 TI - Doxorubicin-based adjuvant chemotherapy in elderly breast cancer patients: the M.D. Anderson experience, with long-term follow-up. AB - BACKGROUND: The purpose of this study was to evaluate the clinical outcome of doxorubicin-based adjuvant chemotherapy in elderly breast cancer patients and to compare results in elderly patients with those in younger patients. PATIENTS AND METHODS: We retrospectively reviewed the records of all patients aged 50 years or older treated in trials of doxorubicin-based adjuvant chemotherapy between 1974 and 1988. Old age was not an exclusion criterion for these trials. Patient characteristics, hematologic and nonhematologic side effects, patterns of recurrence, and causes of death were determined for patients aged 50-64 years and for patients aged 65 years or older, and results were compared between these two groups. Kaplan-Meier survival curves were plotted, and tested by the generalized Wilcoxon test. RESULTS: A total of 390 patients aged 50 years or older were treated with doxorubicin-based adjuvant chemotherapy during the study period. Of these, 325 were aged 50-64 years (group 1), and 65 were aged 65 years or older (group 2). The median follow-up period for group 1 was 185 months (range 29-272+ months), and the median follow-up period for group 2 was 169 months (range 128 240+ months). There were no statistically significant differences between the two groups with respect to performance status, hormone receptor profile, tumor size, nodal status, or type of locoregional therapy. There also were no statistically significant differences between the two groups in recurrence patterns, disease free survival, or overall survival. The granulocyte and platelet nadirs of cycles 1, 3, and 6 were similar between the two groups. No cumulative hematologic side effects were seen in either group. The occurrence of second malignancies was extremely low in both groups. In both groups, the majority of deaths were due to progression of disease. CONCLUSIONS: Adjuvant doxorubicin-based chemotherapy is well tolerated in elderly breast cancer patients who have good performance status and normal cardiac ejection fraction. Adjuvant doxorubicin-based chemotherapy in these patients results in disease-free and overall survival rates similar to those seen in younger patients. PMID- 11205470 TI - Phase II clinical trials of cisplatin-then-paclitaxel and paclitaxel-then cisplatin in patients with previously untreated advanced epithelial ovarian cancer. AB - PURPOSE: To examine the activity and safety of two sequentially scheduled chemotherapy regimens comprising four cycles of paclitaxel (pctx) 200 mg/m2/3 hours then four cycles ofcisplatin (cisDDP) 100 mg/m2, and vice versa, in patients with previously untreated advanced ovarian cancer. PATIENTS AND METHODS: Between January 1994 and February 1996, we recruited 30 patients to the pctx-then cisDDP regimen and 29 to cisDDP-then-pctx, in parallel phase II trials. RESULTS: Both regimens were predictably active with responses seen in 22 of 30 patients (OR 74%; CR 27%, PR 47%) treated with pctx-then-cisDDP, as against 13 of 21 patients (OR 62%; CR 38%, PR 24%) treated with cisDDP-then-pctx. The OR rate to four cycles of pctx (induction) was 43%, with 27% disease progression; the OR to four cycles of cisDDP (induction) was 57%, with 5% progression. However, progression rates across both induction and consolidation phases were 16% (pctx then-cisDDP) and 29% (cisDDP-then-pctx). Both regimens were unacceptably neurotoxic. II patients suffering grade 3 sensory neurotoxicity (5 on pctx-then cisDDP, 6 on cisDDP-then-pctx) and 20 having grade 3 deafness (9 on pctx- then cisDDP, 11 on cisDDP-then-pctx). CONCLUSION: The activity of these sequential regimens justifies their further development using the less neurotoxic platinum analogue carboplatin, perhaps combining paclitaxel with other platinum non-cross resistant drugs. PMID- 11205471 TI - Pancreatic metastasis of a pleuropulmonary blastoma in an adult. AB - Pleuropulmonary blastoma (PPB) is a rare dysontogenetic tumor that usually develops in the first decade of life and has been recognized as a distinct clinico-pathological entity different from the ordinary pulmonary blastoma of adulthood. Since the tumor grows aggressively and tends to metastasize early, physicians have to be aware of late onset of symptoms and uncommon manifestations. We report a case of PPB in a young adult and its recurrence in the pancreas after primary surgical treatment and adjuvant chemotherapy. Keeping in mind the moderate prognosis of PPB in children, accurate assessment and treatment of PPB require a team approach of oncology, radiology and surgery to establish new therapeutic guidelines in the future. PMID- 11205472 TI - Interferon-alpha as first-line therapy for treatment of multicentric Castleman's disease. PMID- 11205473 TI - Radiation myositis: the possible role of gemcitabine. PMID- 11205474 TI - Docetaxel and cisplatin in head and neck cancer. PMID- 11205475 TI - Axillary sentinel node biopsy under local anaesthesia in early breast cancer. PMID- 11205476 TI - [German publications in leading English language journals]. AB - BACKGROUND AND OBJECTIVE: The per capita publication output of German medical research is low compared not only to the English-speaking nations but also to Austria and Switzerland. We assessed the publications from German universities in the leading English language general medical journals: New England Journal of Medicine (NEJM), Lancet, Journal of the American Medical Association (JAMA), and British Medical Journal (BMJ). METHODS: Medline (1988-5/2000) was searched for journal-articles with German origin published in the above journals and manually classified as to institution and speciality. RESULTS: 372 publications from Germany were found. 216 had been published in Lancet, 87 in NEJM, 52 in BMJ, and 17 in JAMA. 58 were excluded (2 from British military hospitals in Germany, 2 from pharmaceutical companies, 2 from physician associations, 18 from non university basic research institutions or government agencies, 3 from non-medical university departments, 30 from non-university hospitals, 1 from a transfusion service of the German Red Cross). The remaining 314 publications were from 34 universities. The most speciality was internal Medicine with 140 university publications, the most represented university was the Ludwig-Maximilians University in Munich with 43 publications. 5 universities had no publications in the analysed journals. CONCLUSION: Large differences were found between the German universities with respect to publications in the leading English Language general medical journals. PMID- 11205477 TI - [Anaplastic astrocytomas of the medulla oblongata. A rare differential diagnosis in orthostatic hypotension]. AB - HISTORY AND PHYSICAL EXAMINATION: A 39-year-old women was admitted for evaluation of dizziness and hypotension. During standing the blood pressure dropped from 130/80 to 80/40 mmHg. Ten weeks before admission she had recurrent cerebral convulsions. Neurological evaluation showed a slight left hemiparesis. Computed tomography of the brain revealed a 1.5 +/- 1 cm cyst in the left tempral region. It was thought that the cause of the recurrent convulsions was alcohol abuse. During the next few weeks orthostatic hypotension increased and she was not able to work. INVESTIGATIONS: At admission abnormal findings included hypotension, horizontal nystagmus, and deviation of the soft palate to the right. After the patient was brought to an upright position during standardized passive tilt testing she showed a defect in the sympathetic limb of the baroreceptor reflex arc. Head magnetic resonance tomography showed a signal-enhancing tumour in the cervicomedullary region. TREATMENT AND CLINICAL COURSE: Before a planned biopsy could be performed the patient died of respiratory arrest. Postmortem examination revealed an anaplastic grade III astrocytoma extending form the pons to the medulla oblongata. CONCLUSION: Upright tilting leads to pooling of blood in the legs. One of the normal compensatory responses is a reflex tachycardia which our patient did not show as a sign of an afferent defect. Patients with orthostatic hypotension as a prominent symptom should be investigated with a standardized tilt test. In special patients, additional neurological investigations are necessary. PMID- 11205478 TI - [Coronary bypass surgery in May-Hegglin anomaly]. AB - HISTORY: Twelve years prior to hospitalization because of a severe bleeding, a 70 year old patient was diagnosed with a May-Hegglin anomaly, which is a rare autosomal dominant inherited form of thrombocytopenia. INVESTIGATIONS: The blood smear contained signs of the May-Hegglin anomaly: Dohle's inclusion bodies and giant platelets. Platelet counts were around 30 G/l. Coronary angiography revealed a highly severe left main stenosis. TREATMENT AND COURSE: Even using maximum drug therapy, angina pectoris could not be stabilized. Therefore emergency coronary artery bypass grafting had to be performed. Before skin incision 3 micrograms/kg DDAVP (Desmopressin) were administered and after extracorporeal circulation 8 units of platelets were transfused. In addition, perioperative coagulation management was performed according to usual standards. There were no bleeding complications. The patient could leave the clinic after 11 days in stable condition. CONCLUSION: Patients showing May-Hegglin anomaly, even with serious thrombocytopenia, can be operated using extracorporal circulation without a high risk of bleeding. PMID- 11205479 TI - [Spring water in hospitals--an alternative drinking water concerns with processed mineral water?]. PMID- 11205480 TI - [Treatment of cystic echinococcosis]. PMID- 11205481 TI - [Herpes B infection in humans]. PMID- 11205482 TI - [Fairness for women scientists and physicians: lessons from the Massachusetts Institute of Technology (MIT)]. PMID- 11205483 TI - [Disturbances in cholesterol metabolism]. PMID- 11205484 TI - Vitamin C and vitamin E supplement use and colorectal cancer mortality in a large American Cancer Society cohort. AB - Some recent epidemiological studies have suggested that use of vitamin C or vitamin E supplements, both of which are important antioxidants, may substantially reduce the risk of colon or colorectal cancer. We examined the association between colorectal cancer mortality and use of individual vitamin C and E supplements in the American Cancer Society's Cancer Prevention Study II cohort. We used proportional hazards modeling to estimate rate ratios among 711,891 men and women in the United States who completed a self-administered questionnaire at study enrollment in 1982, had no history of cancer, and were followed for mortality through 1996. During the 14 years of follow-up, 4404 deaths from colorectal cancer occurred. After adjustment for multiple colorectal cancer risk factors, regular use of vitamin C or E supplements, even long-term use, was not associated with colorectal cancer mortality. The combined-sex rate ratios were 0.89 [95% confidence interval (CI), 0.73-1.09] for 10 or more years of vitamin C use and 1.08 (95% CI, 0.85-1.38) for 10 or more years of vitamin E use. In subgroup analyses, use of vitamin C supplements for 10 or more years was associated with decreased risk of colorectal cancer mortality before age 65 years (rate ratio = 0.48; 95% CI, 0.28-0.81) and decreased risk of rectal cancer mortality at any age (rate ratio = 0.40; 95% CI, 0.20-0.80). Our results do not support a substantial effect of vitamin C or E supplement use on overall colorectal cancer mortality. PMID- 11205485 TI - Reducing bioavailable sex hormones through a comprehensive change in diet: the diet and androgens (DIANA) randomized trial. AB - High serum levels of testosterone and estradiol, the bioavailability of which may be increased by Western dietary habits, seem to be important risk factors for postmenopausal breast cancer. We hypothesized that an ad libitum diet low in animal fat and refined carbohydrates and rich in low-glycemic-index foods, monounsaturated and n-3 polyunsaturated fatty acids, and phytoestrogens, might favorably modify the hormonal profile of postmenopausal women. One hundred and four postmenopausal women selected from 312 healthy volunteers on the basis of high serum testosterone levels were randomized to dietary intervention or control. The intervention included intensive dietary counseling and specially prepared group meals twice a week over 4.5 months. Changes in serum levels of testosterone, estradiol, and sex hormone-binding globulin were the main outcome measures. In the intervention group, sex hormone-binding globulin increased significantly (from 36.0 to 45.1 nmol/liter) compared with the control group (25 versus 4%,; P < 0.0001) and serum testosterone decreased (from 0.41 to 0.33 ng/ml; -20 versus -7% in control group; P = 0.0038). Serum estradiol also decreased, but the change was not significant. The dietary intervention group also significantly decreased body weight (4.06 kg versus 0.54 kg in the control group), waist:hip ratio, total cholesterol, fasting glucose level, and area under insulin curve after oral glucose tolerance test. A radical modification in diet designed to reduce insulin resistance and also involving increased phytoestrogen intake decreases the bioavailability of serum sex hormones in hyperandrogenic postmenopausal women. Additional studies are needed to determine whether such effects can reduce the risk of developing breast cancer. PMID- 11205486 TI - Diet and cancer: one view at the start of the millennium. AB - The large differences in cancer rates among countries, striking changes in these rates among migrating populations, and rapid changes over time within countries indicate that some aspect of lifestyle or environment is largely responsible for the common cancers in Western countries. Dietary fat has been hypothesized to be the key factor because national consumption is correlated with the international differences, but these correlations are potentially confounded by other aspects of Western lifestyles. Detailed analyses in large prospective studies have not supported an important role of dietary fat. Instead, positive energy balance, reflected in early age at menarche and weight gain as an adult, is an important determinant of breast and colon cancers, consistent with numerous studies in animals. Physical inactivity has also been shown to be a risk factor for these diseases, and in part accounts for the international differences in cancer rates. Although the percentage of calories from fat in the diet does not appear related to risk of colon cancer, greater risks have been seen with higher consumption of red meat, suggesting that factors other than fat per se may be important. In many case-control studies a high consumption of fruits and vegetables has been associated with reduced risks of numerous cancers, but recent prospective studies suggest these associations may have been overstated. Among the factors in fruits and vegetables that have been examined in relation to cancer risk, present data most strongly support a benefit of higher folic acid consumption in reducing risks of colon and breast cancers. These findings have been bolstered by an association between incidence of colon cancer and a polymorphism in the gene for methylenetetrahydrofolate reductase, an enzyme involved in folic acid metabolism. The benefits of folic acid appear strongest among persons who regularly consume alcohol, which itself is associated with risk of these cancers. Numerous other aspects of diet are hypothesized to influence the risks of cancers in Western countries, but for the moment the evidence is unclear. Two decades of effort in developing, evaluating, and refining methods of dietary assessment have laid the groundwork for further insights into the role of diet in cancer etiology that will emerge from the more than 30 large prospective studies that are currently underway. PMID- 11205487 TI - Factors associated with perceived risk in automotive employees at increased risk of colorectal cancer. AB - Risk perception may be an important motivator of health-related behaviors. To develop effective risk communication messages, it is important to understand both the patterns of association between perceived risk and health-related behaviors as well as the correlates of risk perception. Very little is known about whether correlates of risk perception are similar in cross-sectional data compared with prospective data. Furthermore, there are scant data on consistency of correlates of risk perception across groups who vary in objective medical risk. If correlates differ, it would underscore the need to tailor intervention messages based on subgroup characteristics as well as increase awareness of the limitations of basing intervention messages only on cross-sectional data. We analyzed data on a subset of 5042 employees who participated in The Next Step Trial, a randomized health promotion trial to encourage colorectal cancer screening and dietary change. We restricted our analysis to only those automotive workers who were white, male, and did not have colorectal cancer (4477/5042) and who returned surveys both at baseline (2,684/4,477) and at year 2 of follow-up (1955/2684). Initial analyses detected interactions between a history of polyps and several of the other covariates. Therefore, univariate and multivariable analyses were conducted separately for men with and without a personal history of colorectal polyps. Within each of the four subgroups (those with or without polyps in the baseline or follow-up analyses), we examined associations between perceived risk measured at baseline (cross-sectional analyses) and at year 2 of follow-up (prospective analyses) in relation to intervention group status, demographic, medical history, psychosocial, and worksite characteristics measured at baseline. To assess the predictive ability of the models, we computed sensitivity and specificity as measures of each model's ability to correctly classify men into their respective subgroup. Although there was no association between perceived risk and intervention group status in the four subgroups analyzed, we included intervention group status as a covariate in all analyses. At baseline (cross-sectional analyses) among men with and without a history of polyps, perceived risk was positively associated with family history of colorectal polyps or cancer, family support for screening, and worry about being diagnosed with colorectal cancer. In addition, for men without polyps, perceived risk was positively associated with being a current smoker. At year 2 of follow up (prospective analyses) for men with and without polyps, perceived risk at year 2 was positively associated with family history and baseline perceived risk and was negatively associated with having a normal screening examination or no examinations during the trial. In addition, for men with polyps, perceived risk was positively associated with belief in the salience and coherence of screening and with intention to be screened and was negatively associated with access to screening at the worksite. Specificity was higher than sensitivity in three of four subgroups and was >65% in all subgroups. Except for family history, messages to influence perceived risk would emphasize different factors, depending on whether associations were based on baseline or follow-up data and depending on whether men reported a personal history of polyps. For example, although intervention messages using baseline data would emphasize the same factors for men with or without polyps, messages based on follow-up data would emphasize psychosocial characteristics, such as salience and coherence of screening and intention for men with a history of polyps but not for men without. Our findings support the need to delineate subgroups in the study population to target and tailor health-related messages based on respondent characteristics. Our findings also underscore the need to base health-related messages on prospective data as well as cross-sectional data to better address health-related beliefs and behaviors. PMID- 11205488 TI - High-risk and multiple human papillomavirus infections associated with cervical abnormalities in Japanese women. AB - To estimate the risk of human papillomavirus (HPV) infection for cervical malignancies, we conducted a case-control study in Japan. Abnormal cervical cell (366) and normal cell samples (1562) were tested for the presence of HPV DNA using a new PCR-based test (LCR-E7 PCR). When single HPV infections were considered, 26 different HPV types were identified in normal cervices and in low grade squamous intraepithelial lesions (LSIL); whereas HPV-16, -18, -31, -33, 35, -45, -51, -52, -56, -58 and -67 were detected in high-grade squamous intraepithelial lesions (HSIL) and in squamous cell carcinoma (SCC) of the cervix, and HPV-16 and -18 were detected in cervical adenocarcinoma. HPV-6 and 11 were detected in condyloma acuminatum tissue. In HSIL and SCC, HPV-16 was the most prevalent type and HPV-51, -52, and -58 were the next most prevalent; whereas HPV-39, -59, and -68 were not detected. Analysis by odds ratio (OR) revealed that HPV-11, -39, -42, -44, -53, -59, -62, and -66 (HPV-66: OR,139; 95% confidence interval (CI) = 6.7-168) were associated with LSIL; HPV-16, -18, -31, 51, -52 and -58 (HPV-16: OR, 69; 95%CI = 36-131) were associated with SCC; and HPV-16 and -18 (OR, 94; 95% CI = 28-317) were associated with adenocarcinoma. Multiple HPV infection was associated with LSIL (OR, 24; 95%CI = 13-44), HSIL (OR, 16; 95%CI = 8.4-32), and SCC (OR, 8.3; 95%CI = 3.2-22), although the prevalence decreased with the grade of the lesions. All results suggest that HPV 6 and -11 are condyloma types, HPV-16, -18, -31, -51, -52, -58, and perhaps -33, 35, -45, -56, and -67, are the high-risk HPV types, and many other types are LSIL associated types in Japan. HPV typing and detection of multiple HPV infections in clinical samples may be useful as surrogate markers for cervical cell abnormalities. PMID- 11205489 TI - Phase I pharmacokinetic study of tea polyphenols following single-dose administration of epigallocatechin gallate and polyphenon E. AB - Green tea has been shown to exhibit cancer-preventive activities in preclinical studies. Its principal active components include epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin (EC), and epicatechin gallate, of which EGCG is the most abundant and possesses the most potent antioxidative activity. We performed a Phase I pharmacokinetic study to determine the systemic availability of green tea catechins after single oral dose administration of EGCG and Polyphenon E (decaffeinated green tea catechin mixture). Twenty healthy subjects (five subjects/dose level) were randomly assigned to one of the dose levels (200, 400, 600, and 800 mg based on EGCG content). All subjects were randomly crossed over to receive the two catechin formulations at the same dose level. Blood and urine samples were collected for up to 24 h after oral administration of the study medication. Tea catechin concentrations in plasma and urine samples were determined using high-performance liquid chromatography with the coulometric electrode array detection system. After EGCG versus Polyphenon E administration, the mean area under the plasma concentration-time curves (AUC) of unchanged EGCG were 22.5 versus 21.9, 35.4 versus 52.2, 101.9 versus 79.7, and 167.1 versus 161.4 min x microg/ml at the 200-, 400-, 600-, and 800-mg dose levels, respectively. EGC and EC were not detected in plasma after EGCG administration and were present at low/undetectable levels after Polyphenon E administration. High concentrations of EGC and EC glucuronide/sulfate conjugates were found in plasma and urine samples after Polyphenon E administration. There were no significant differences in the pharmacokinetic characteristics of EGCG between the two study medications. The AUC and maximum plasma concentration (Cmax) of EGCG after the 800-mg dose of EGCG were found to be significantly higher than those after the 200- and 400-mg dose. The AUC and Cmax of EGCG after the 800-mg dose of Polyphenon E were significantly higher than those after the three lower doses. We conclude that the two catechin formulations resulted in similar plasma EGCG levels. EGC and EC were present in the body after the Polyphenon E administration; however, they were present predominantly in conjugated forms. The systemic availability of EGCG increased at higher doses, possibly due to saturable presystemic elimination of orally administered green tea polyphenols. PMID- 11205490 TI - Saliva as a medium for investigating intra- and interindividual differences in sex hormone levels in premenopausal women. AB - Repeated measurement of ovarian steroids in saliva could provide an advantage in studies estimating long-term sex steroid exposure in premenopausal women, by reducing the measurement error associated with collection of serum or urine samples. We previously reported on characteristics of ultrasensitive RIAs adapted for extraction-free measurement of estradiol (E2) and progesterone (PG) in saliva. The purpose of the present study was to evaluate the consistency of E2 and PG levels in saliva in the same women across menstrual cycles, and to compare this with the variation observed between women. We also evaluated the effect of altering the number of consecutive daily samples considered and the method for locating a particular cycle day in relation to ovulation (day 0). Study participants included 12 healthy women who provided daily saliva samples for two consecutive, ovulatory menstrual cycles. A single midluteal serum sample was collected 7-8 days after detection of a luteinizing hormone (LH) peak in urine. We plotted individual cycle profiles and computed intraclass correlation coefficients (ICC) for various definitions of peak and cumulative daily hormone level. For peak PG, determined as the maximal running 3-day mean, ICC was 0.68. For cumulative PG, based on 8 consecutive cycle days (+2 to +9), ICCs were 0.72 0.76 when reverse dating LH peak or rise in salivary PG determined day 0. For E2, ICCs ranged from 0.74 to 0.79 by various dating methods for the 5 preovulatory days (-4-0), and from 0.85 to 0.92 for the 15 days about the center of the cycle (-6 to +8). With exclusion of just the first 5 days of the cycle, the ICC for E2 was 0.91. For both E2 and PG, selection of 5 or 7 days for the estimation of the midluteal mean level provided separation of within and between subject variance that was comparable with a LH-timed serum sample. These results indicate that daily saliva samples can be combined to clarify the interindividual differences in E2 and PG levels in premenopausal women, and that these interindividual differences may be greater than previously imagined. PMID- 11205491 TI - The repeatability of serum carotenoid, retinoid, and tocopherol concentrations in specimens of blood collected 15 years apart. AB - Community-wide programs to collect blood for a research serum bank were carried out in Washington County, Maryland in 1974 and 1989. Of the 8395 persons who participated in both programs, 64 were controls in a nested case-control study of the association of antioxidant micronutrients with subsequent breast cancer, and 30 and 166 were controls in similar studies of lung and prostate cancer. Assay results for five carotenoids, two retinoids, and two tocopherols in samples of blood collected 15 years apart were thus available for comparisons of micronutrient concentrations. The mean Spearman rank order correlation coefficient for all comparisons was 0.44, with two coefficients greater than 0.60 and two less than 0.30. Blood pressure readings at the two blood collections had a mean rank order correlation coefficient of 0.46. Because blood pressure readings in 1974 were shown to be significantly predictive of atherosclerosis 15 18 years later, the present results suggest that ranked concentrations of antioxidant micronutrients from a single sample are sufficiently representative to be used as predictors of subsequent concentrations and are thus suitable for assessment as risk factors for subsequent illnesses. PMID- 11205492 TI - Hypomethylation of p53 in peripheral blood DNA is associated with the development of lung cancer. AB - Alterations in DNA methylation have been associated with cancers at almost all tumor sites and represent one of the most consistent changes in neoplastic cells. The underlying etiological mechanisms for alteration of DNA methylation patterns are not understood, but experimental studies in animals suggest potential environmental and genetic influences. The purpose of this study was to investigate whether DNA hypomethylation in peripheral blood DNA (potentially representing status at the lung) was associated with increased risk for the development of lung cancer. We evaluated genome-wide and p53 gene-specific hypomethylation in 100 lung cancer cases and controls selected from a large clinical trial of male smokers, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Genome-wide methylation status was assessed using the in vitro methyl acceptance capacity assay and p53 gene-specific methylation status using the HpaII quantitative PCR assay. Hypomethylation was evaluated as a risk factor using multivariate conditional logistic regression analyses. Genome-wide methylation status was unrelated to lung cancer risk; the odds ratio was 1.25 and the 95% confidence interval was 0.48-3.21 for those in the highest versus lowest quartile of hypomethylation status. Hypomethylation of the p53 gene in exons 5-8, the hypermutable region, was associated with a 2-fold increased risk for lung cancer (odds ratio, 2.20; 95% confidence interval, 1.04-4.65), whereas there was no risk increase for hypomethylation at exons 2-4, a region of the gene not known for its mutability or functional significance in cancer. Our results indicate that hypomethylation status within exons 5-8 of p53 from peripheral lymphocyte DNA may be a relevant predictor of lung cancer among male smokers. PMID- 11205493 TI - Histological classification of gastric adenocarcinoma for epidemiological research: concordance between pathologists. AB - Epidemiology of gastric adenocarcinoma suggests that intestinal-type and diffuse type cancers develop through distinct causal pathways. To examine the differences in risk factors and molecular changes between the histological types, reliable data on histological typing are essential. We evaluated the concordance between two pathologists in assessment of 95 gastric adenocarcinomas for Lauren classification and tumor grade. Two pathologists, each blinded to the other's assessment, reviewed H&E-stained slides of gastric tumor. The responses of the two pathologists for histological type were considered as concordant if they fell on one of the three categories (intestinal type, diffuse type, or other). Tumor grade was classified into three categories (well, moderately, or poorly differentiated). The pathologists agreed on the classification of histological type for 71 of 92 (77%) tumors. Kappa coefficient was 0.59 (95% confidence interval, 0.44-0.73). Concordance for tumor grade was 87%, with a kappa coefficient of 0.72 (95% confidence interval, 0.57-0.87). Both observed concordance and kappa coefficient for histological type and tumor grade were similar across three calendar periods of study. Interobserver agreement was virtually identical between tumors with biopsy specimens only and those with surgical specimens. Although the level of disagreement for histological type observed in this study is comparable with that in other studies, the resulting misclassification would lead to the reduction in observed differences in prevalence and odds ratio estimates between two histological types. PMID- 11205496 TI - Disposable, stable media for reproducible surface-enhanced Raman spectroscopy. AB - Large numbers of identical and stable SE(R)RS [surface-enhanced (resonance) Raman]-active media, which are convenient to handle and manipulate but sufficiently inexpensive that they can be used once and then discarded, have been prepared by isolating nanoparticles from Ag and Au sols in hydrophilic polymer gels. The preparation simply involves mixing a suitable polymer with the sol to give a viscous suspension that can be coated onto a substrate and dried to form a hard translucent film. The films remain inactive until they are treated with aqueous analyte solution, which causes the film to swell and brings the analyte into contact with the active metal particles. The swollen films give strong SERS spectra which are effectively identical to those obtained from simple sols. The advantage of this method is that the dried polymers can be stored indefinitely before use and that they give a high degree of spectral reproducibility. PMID- 11205495 TI - Breast cancer risk and "delayed" primary Epstein-Barr virus infection. AB - Parallel to its established causal association with both infectious mononucleosis (IM) and young adulthood Hodgkin disease (YAHD), we propose a hypothesis that "delayed" primary EBV infection (i.e., primary infection occurring during adolescence or adulthood) is associated with elevated breast cancer risk. We evaluated this hypothesis with two investigations, one descriptive and the other analytic. The descriptive study used international/United States cancer registry data to assess the association between incidence rates of breast cancer and those of YAHD. The incidence rates of the seemingly unrelated neoplasms were strongly correlated (correlation coefficients of 0.74 and 0.88 for international and United States data, respectively; these were higher than the correlation coefficients of YAHD with two other cancers that we considered). Populations with higher incidence rates corresponded to those with higher likelihood of delayed primary EBV infection. The analytical study was based on a population-based case control study of breast cancer in middle-aged women. Age-adjusted odds ratios of breast cancer in women who reported a history of IM, relative to women who did not, increased monotonically from 0.55 [95% confidence interval (CI), 0.05-6.17] for women with 0-9 years of age at IM onset to 2.67 (CI, 1.04-6.89) for women with > or =25 years of age at IM onset (P = 0.016). An older age at tonsillectomy, another surrogate of delayed EBV exposure, was also associated with increased risk of breast cancer: odds ratios, 0.92 (CI, 0.57-1.48) and 1.76 (CI, 1.15-2.69) for women with tonsillectomy at 0-4 years of age and > or =15 years of age, respectively (P = 0.018). Adjusting for additional potential confounders did not modify the associations appreciably. The implications of the findings and a potential biological mechanism are presented. PMID- 11205494 TI - KRAS mutations are not predictive for progression of preneoplastic gastric lesions. AB - Individuals with atrophic gastritis (n = 863) were recruited to participate in a chemoprevention trial in Narino, Columbia. The volunteers were randomly assigned to intervention therapies, which included antibiotic treatment for Helicobacter pylori infection, and then daily dietary supplementation with antioxidant micronutrients in a 2(3) factorial design. Biopsies were obtained according to a specified protocol from designated areas in the stomach for each individual at baseline (before intervention therapy), at year 3, and at year 6. A systematic sample of 160 participants was selected from each of the eight treatment combinations, and the first exon of KRAS was examined for mutations. At year 3, the data indicated that individuals with KRAS mutations in their baseline premalignant stomach biopsies were 3.74 times as likely to progress to a higher premalignant stage than those who lacked baseline mutations (P = 0.04; C. Gong et al., Cancer Epidemiol. Biomark. Prevy. 8:167-171, 1999). However, after 6 years, baseline KRAS mutations failed to predict histological progression. Also, KRAS mutation in 72-month biopsies did not predict histological progression. PMID- 11205497 TI - A new fluorimetric method for the determination of formaldehyde in air based on the liquid droplet sampling technique. AB - A new, simple, sensitive, selective and in-field fluorimetric method for the determination of formaldehyde is proposed. The reaction of formaldehyde with hydralazine in acidic medium, heating on a boiling water-bath for 25 min, produces s-triazolo[3,4-a]phthalazine (Tri-P). The fluorescence intensity of the product formed (Tri-P) was determined at lambda em = 389 nm with lambda ex = 236 nm. The fluorescence intensity is linear over a formaldehyde concentration range of 1.2-33.0 micrograms l-1. The proposed method was applied successfully to the determination of formaldehyde sampled from the atmosphere using the liquid droplet technique. Formaldehyde vapour in a wind tunnel was produced by a mean of permeater. A linear curve was obtained between the concentration in the wind tunnel and that in the droplet. The detection limit for formaldehyde was 2.0 micrograms l-1 with RSDs varying from 3 to 12% in ambient air, using a droplet correction solution (boric acid and hydralazine). The effect of interfering substances on the determination shows that most cations and anions did not interfere. The results obtained were satisfactory compared with a reference method. PMID- 11205498 TI - Determination of Co(II) by chemiluminescence after in situ electrochemical pre separation on a flow-through mercury film electrode. AB - A novel method of electrochemical pre-separation of Co(II) before detection by chemiluminescence is reported together with the associated instrumentation. The Co(II) ions were selectively pre-separated on a mercury film electrode (MFE) by on-line reduction, then the accumulated metal was oxidised and selectively stripped back into the flowing solution as Co(II). These secondary ions were quantified as a result of their catalytic activity on the chemiluminescent reaction between luminol and hydrogen peroxide that was also induced on-line. The whole sequence was carried out in an automated flow-through system, in which the electrochemical pre-separation of metals was performed in either continuous flow or flow injection analysis (FIA) regimes. The scope of the method, both in terms of selectivity and sensitivity, has been demonstrated and the quantitative determination of Co(II) by the proposed method has been investigated. For a period of continuous flow pre-separation of 4 min, the calibration curve for Co(II) was linear up to a concentration of 100 micrograms l-1, the relative standard deviation was 4% at the 20 micrograms l-1 level and the limit of detection was 0.5 microgram l-1 (at the 3 sigma level). The method was applied to the determination of the cobalt content in a high purity iron sample. PMID- 11205499 TI - The generation of concentration gradients using electroosmotic flow in micro reactors allowing stereoselective chemical synthesis. AB - The stereoselective control of chemical reactions has been achieved by applying electrical fields in a micro reactor generating controlled concentration gradients of the reagent streams. The chemistry based upon well-established Wittig synthesis was carried out in a micro reactor device fabricated in borosilicate glass using photolithographic and wet etching techniques. The selectivity of the cis (Z) to trans (E) isomeric ratio in the product synthesised was controlled by varying the applied voltages to the reagent reservoirs within the micro reactor. This subsequently altered the relative reagent concentrations within the device resulting in Z/E ratios in the range 0.57-5.21. By comparison, a traditional batch method based on the same reaction length, concentration, solvent and stoichiometry (i.e., 1.0:1.5:1.0 reagent ratios) gave a Z/E in the range 2.8-3.0. However, when the stoichiometric ratios were varied up to ten times as much, the Z/E ratios varied in accordance to the micro reactor i.e., when the aldehyde is in excess, the Z isomer predominates whereas when the aldehyde is in low concentrations, the E isomer is the more favourable form. Thus indicating that localised concentration gradients generated by careful flow control due to the diffusion limited non-turbulent mixing regime within a micro reactor, leads to the observed stereo selectivity for the cis and trans isomers. PMID- 11205500 TI - Sampling of kidneys from cattle and pigs for cadmium analysis. AB - Cadmium accumulates in proximal tubule cells causing a gradient of cadmium through the kidney, which is important to consider when sampling kidney tissue for cadmium analysis. In this study different sampling techniques of cattle and pig kidneys have been tested. Cadmium was determined by dry ashing-FAAS (detection limit 6.0 micrograms l-1, BCR (Community Bureau of Reference) No. 186 3.1 +/- 0.17 mg kg-1 (mean +/- s), laboratory quality sample (LQS) 495 +/- 17 micrograms kg-1) and microwave digestion-graphite furnace AAS (detection limit 0.24 microgram l-1, BCR No. 186 2.7 +/- 0.16 mg kg-1, LQS 444 +/- 14 micrograms kg-1) in homogenates, slices, and in cortex, intermediate and medulla zones of bovine and porcine kidneys. The bovine kidney lobulus cortex, intermediate zone, and medulla contained 70, 28 and 2% of the total cadmium content, and the relative weights of the zones were 53, 35 and 12%, respectively. The cadmium concentration in bovine cortex, intermediate zone and medulla was 1.37 +/- 7, 0.79 +/- 0.06 and 0.10 +/- 0.06 times the calculated homogenate concentration. Pig renal cortex, intermediate zone and medulla, contained 73, 26 and 0.5% respectively of the total cadmium content, and the relative weights were 63, 36 and 2.4%, respectively. The cadmium concentration in porcine cortex, intermediate zone and medulla was 1.14 +/- 0.05, 0.78 +/- 0.09 and 0.23 +/- 0.11 times the calculated homogenate concentration. Freezing of pig kidney caused a slight redistribution of cadmium from cortex to medulla. The results show that sampling technique is of greater importance for the determination of cadmium in bovine kidney than in pig kidney. A well described method for sampling of kidney is necessary to make it possible to compare results. To detect small differences in renal Cd levels between groups, as, e.g., in the case of biological monitoring of Cd exposure, sampling of the outer cortex is suggested as an optimal method. PMID- 11205501 TI - Continuous and stopped flow injection for catalytic determination of total iodine in urine. AB - This paper describes the use of flow injection (FI) techniques for the determination of iodine in urine, based on the catalytic effect of iodide in the redox reaction between Ce(IV) and As(III). The proposed procedures minimize errors in the conventional batch method arising from the reading of absorbance at a fixed time after addition of Ce(IV) reagent. Two FI systems, for the continuous and stopped modes of operation were assembled. In the continuous-FI system, a thermostated bath was used to increase the sensitivity. However this is not necessary for the stopped-FI system. The two systems are comparable in terms of sensitivity, sample throughput and detection limit. The continuous-FI and the stopped-FI exhibited detection limits (3 sigma) of 2.3 and 3 micrograms I l-1 respectively. Both systems have equal sample throughputs of 35 samples h-1. Calibration plots for both techniques are linear. The FI procedures provide very short analysis times compared to the batch procedure. Using the linear regression test, there is no significant difference between the results from the four methods, i.e., continuous-FI, stopped-FI, conventional method and ICP-MS. The proposed methods are readily applicable for automation and can be an alternative to the conventional procedure for the survey of the iodine deficiency disorder. A condition for sample digestion is also proposed to reduce the amount of chloric acid required for complete digestion. Kinetic information of the reaction can also be obtained from the stopped flow mode. PMID- 11205502 TI - Use of the correct blank test in the determination of COD and AOX in bleached kraft mill D stage effluents. AB - A study of four types of blank, two of which (the placebo blank and the method blank) are amenable to direct measurements and the other two [the total Youden blank (TYB) and system blank] to extrapolation, revealed the need to use a correct blank test, the TYB, in order to eliminate the constant error component. The conclusions drawn here are demonstrated for the microcoulometric determination of adsorbable organic halogen (AOX), according to Scandinavian standard SCAN-W 9:89, and in the spectrophotometric determination of chemical oxygen demand (COD) following a closed reflux spectrophotometric method. These environmental analytical parameters (AOX and COD) were determined in two different bleached kraft mill effluents: one from stage D (100% ClO2) of the bleaching sequence AOD of the elemental chlorine-free type and the other for the chlorination step, the first in the conventional sequence (D20C80)(E0)D1D2, applied to kraft pulp from Populus spp. PMID- 11205503 TI - Electric field-induced mobilisation of multiphase solution systems based on the nitration of benzene in a micro reactor. AB - This paper describes the electric field-induced flow characteristics of multiphase solutions in a micro reactor device using the nitration of benzene as a model process. Photolithographic and wet etching techniques were used to fabricate the micro reactor (channels, 200 microns id, 100 microns deep) in a borosilicate glass substrate. The results focus specifically on the flow parameters of reagents/reactants (i.e., voltage, solution concentration and pH ranges and current-voltage relationships) used in this study. The benzene was introduced and mobilised by electroosmotic flow (EOF), as a microemulsion using an appropriate surfactant (sodium dodecyl sulfate), whilst the nitronium ions, produced in situ from mixed H2SO4-HNO3 (the nitrating agent), underwent electrophoretic-induced (electrokinetic) mobility. A co-surfactant, butan-1-ol, was used owing to (a) its relative solubility in the aqueous surfactant solution, (b) its ability to aid the solubilization of benzene, (c) the provision of a water-rich (oil-in-water) rather than oil-rich (water-in-oil) microemulsion system and (d) its lack of significant adverse effects on the EOF. The optimum conditions used for the nitration of benzene within the micro reactor were a run of the microemulsion as main reagent stream, then three 30 s segmented injections of mixed acid, with a 5 s push of the microemulsion into the system after each injection, and then a 60 s stopped-flow reaction time before driving reaction product segments to a collection reservoir. PMID- 11205504 TI - Microfabricated reactors for on-chip heterogeneous catalysis. AB - Microfabricated devices constructed from glass and polydimethylsiloxane with integral heaters are described, which can be used for heterogeneous catalysis reactions. Sulfated zirconia is used as the catalyst in an open channel reactor, with either a syringe pump or electroosmotic flow being used to deliver the reactants. The results clearly demonstrate that very high conversion efficiencies are possible, however, the thermodynamics of the reactions are the same as in bulk systems. Ethanol and hexanol are dehydrated to ethene and hexene, respectively, with conversion efficiencies approaching 100%, and the esterification of ethanol is investigated. Yields of approximately 30% ethyl acetate are obtained by gas chromatographic analysis. This is the first time such a method for fabricating a catalyst micro reactor has been reported, yet it demonstrates sufficient robustness and resistance to leakage. The use of electroosmotic flow in a heated catalyst reactor is a significant advancement in reactor design. PMID- 11205505 TI - Microchip-based synthesis and analysis: control of multicomponent reaction products and intermediates. AB - A miniaturised-SYNthesis and Total Analysis System (mu SYNTAS) was used for the solution-phase synthesis and on-line analysis (TOF-MS) of Ugi multicomponent reaction (MCR) products. This approach provides an unusually high degree of control of the MCR and delivers detailed, novel information on reaction intermediates in real-time. Specifically, the Ugi 4 component condensation (4CC) involving the reaction of an amine, acid, aldehyde and isocyanide species was performed at room temperature in a controllable fashion. Furthermore, observation of the nitrilium intermediate, cyclohexyl(2-piperidin-1-ylethylidyne)ammonium chloride, is presented for the first time. PMID- 11205506 TI - Altering the selectivity of inorganic anion separations using electrostatic capillary electrophoresis. AB - A new method for altering the selectivity of inorganic anion separations in capillary electrophoresis is described. Addition of the zwitterionic surfactant 3-(N,N-dimethyldodecylammonio)propane sulfonate (DDAPS) to the background electrolyte modifies the migration order via electrostatic ion chromatography type interactions. Variation of the DDAPS surfactant concentration from 4 to 120 mM monotonically alters the selectivity from electrophoretic mobility based to that of electrostatic ion chromatography, without increasing Joule heating. This technique was applied to the determination of nitrate, nitrite, bromide and iodide in artificial seawater. Detection limits for the anions in 1:5 diluted seawater were 11, 5, 7 and 11 microM, respectively. PMID- 11205507 TI - Fluorimetric determination of isatin in human urine and serum by liquid chromatography postcolumn photoirradiation. AB - For the fluorimetric determination of isatin in human urine and serum, HPLC postcolumn photoirradiation using a mobile phase has been developed. Isatin in the urine or serum sample was separated on a Capcell Pak C1 column (250 x 4.6 mm id). The mobile phase consisted of 70 mmol l-1 phosphate buffer (pH 7.2) tetrahydrofuran (85 + 15% v/v) containing 5 mmol l-1 hydrogen peroxide, which was irradiated with germicidal light to induce fluorescence (lambda ex 302 nm, lambda em 418 nm). The addition of tetrahydrofuran to the mobile phase led to the peaks showing good separation as well as increased sensitivity. The calibration graph for isatin was linear over the range of 0.16-10.7 ng. The pretreatment of the acidified urine or serum samples consisted of diluting steps or deproteinizing steps using perchloric acid, respectively. The mean recovery of isatin from urine and serum was greater than 94%. PMID- 11205509 TI - Enhanced surface plasmon resonance immunosensing using a streptavidin biotinylated protein complex. AB - In this paper, we present a novel strategy for improving the sensitivity of surface plasmon resonance immunosensing using a streptavidin-biotinylated protein complex. This amplification strategy is based on the construction of a molecular complex between streptavidin and biotin labeled protein. The complex can be formed in a cross-linking network of molecules so that the amplification of the response signal will be realized due to the big molecular size of the complex. The results show that the amplification strategy causes a dramatic improvement of the detection sensitivity. hIgG protein could be detected in the range of 0.005 10 micrograms ml-1. PMID- 11205508 TI - Tris(2,2'-bipyridine)ruthenium(II) electrogenerated chemiluminescence of alkaloid type drugs with solid phase extraction sample preparation. AB - An electrogenerated chemiluminescence (ECL) method for the determination of pethidine, atropine, homatropine and cocaine is described. The optimum conditions were found to be similar for all of these compounds although the ECL emission intensity for cocaine was an order of magnitude lower than for pethidine due to their different chemical structures. Linear calibrations were obtained for all the compounds at pH 10 in borate buffer (0.05 mol l-1) at 1.3 V. Limits of detection of 6.8 x 10(-8), 2.2 x 10(-7), 3.2 x 10(-7) and 6.5 x 10(-7) mol l-1, respectively, were achieved for pethidine, atropine, homatropine and cocaine in standard solutions. Solid-phase extraction was used to separate the drugs from their matrix and the method was applied to the determination of spiked urine samples. The limits of quantitation for pethidine, atropine, homatropine and cocaine in urine were 1.0 x 10(-6), 2.0 x 10(-6), 2.0 x 10(-6) and 4.0 x 10(-6) mol l-1, respectively, with recoveries of between 90 and 110%. PMID- 11205510 TI - Determination of low concentrations of benzene in urine using multi-dimensional gas chromatography. AB - A method for the determination of benzene in urine of occupationally or environmentally exposed persons was developed. The method was based on dynamic headspace, preconcentration on a solid sorbent, followed by thermal desorption and gas chromatographic determination. To achieve sufficient selectivity, we used multi-dimensional gas chromatography in combination with the inexpensive and robust flame ionisation detector. The limit of detection was 7 ng l-1 and the limit of quantification was 23 ng l-1. The linearity was good (correlation coefficient 0.999) in the range examined (20-4000 ng l-1) and the repeatability was 9%. The average recovery at low concentrations (20-400 ng l-1) was 86%. Analysis of a certified reference material of benzene in water, traceable to NIST, did not differ significantly from the certified value. Samples, frozen (-20 degrees C) in glass bottles sealed with Teflon-silicon septa, were stable for 1 year and refrigerated samples (4 degrees C) for at least 1 week. Loss of benzene during the collection and transfer of urine was investigated and found to be acceptable. The method is a cost effective and robust alternative to GC-MS and permits reliable quantification of occupational exposure and, in most cases, also of urine concentrations that can be expected from environmental exposure. PMID- 11205511 TI - Gas chromatographic determination of pesticides in vegetable samples by sequential positive and negative chemical ionization and tandem mass spectrometric fragmentation using an ion trap analyser. AB - A selective and sensitive chromatographic method is described for the determination of nine organochlorine and organophosphorus pesticides in vegetable samples by gas chromatography-mass spectrometry. The proposed method combines the use of positive and negative chemical ionisation and tandem mass spectrometric fragmentation, resulting in a significant increase in selectivity and allowing the simultaneous confirmation and quantification of trace levels of pesticides in complex vegetable matrices. Parameters relative to ionisation and fragmentation processes were optimised to obtain maximum sensitivity. Repeatability and reproducibility studies yielded relative standard deviations lower than 25% in all cases. Identification criteria, such as retention time and relative abundance of characteristic product ions, were also evaluated in order to guarantee the correct identification of the target compounds. The method was applied to real vegetable samples to demonstrate its use in routine analysis. PMID- 11205512 TI - Searching the Porphyromonas gingivalis genome with peptide fragmentation mass spectra. AB - An approach is described for genomic database searching based on experimentally observed proteolytic fragments, e.g., isolated from 1D or 2D gels or analyzed directly, that can be applied to unfinished prokaryotic genomic data in the absence of annotations or previously assigned open reading frames (ORFs). This variation on the database search is in contrast to the more familiar use of peptide mass spectral fragmentation data to search fully annotated inferred protein databases, e.g., OWL or SWISS-PROT. We compared the SEQUEST search results from a six reading frame translation of the Porphyromonas gingivalis genome DNA sequence with those from computationally derived ORFs created using publicly available genomics software tools. The ORF approach eliminated many of the artifacts present in output from the six reading frame search. The method was applied to uninterpreted tandem mass spectrometric data derived from proteins secreted by the periodontal pathogen Porphyromonas gingivalis in response to the gingival epithelial cell environment, a model system for the study of host pathogen interactions relevant to human periodontal disease. PMID- 11205513 TI - Measurement of 237Np in environmental water samples by accelerator mass spectrometry. AB - Accelerator mass spectrometry (AMS) was used to measure 237Np in environmental water samples extracted from Irish Sea sediments. The samples were of limited volume (approximately 700 ml) and of low activity (0.06-0.79 mBq l-1; 2.30-30.3 pg l-1). AMS proved to have the required sensitivity for measuring these samples, and was in principle capable of measuring much smaller amounts, as low as 0.4 microBq (3.9 x 10(7) atoms). However, the background level in the procedural blanks showed that there was a systematic low level 237Np contamination of each sample, arising from the 239Np yield monitor used in the separations procedure, which effectively increased the detection limit of these analyses. PMID- 11205514 TI - Electrochemical detection of sequence-specific DNA using a DNA probe labeled with aminoferrocene and chitosan modified electrode immobilized with ssDNA. AB - The electrochemical detection of sequence-specific DNA using a DNA probe labeled with aminoferrocene (AFC) is reported. Sample ssDNA was immobilized on a chitosan modified glassy carbon electrode. A sequence-known DNA with 256 bp [obtained by polymerase chain reaction (PCR)] was successfully labeled with the electro-active reagent AFC by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide for the first time. This DNA probe labeled with AFC was applied to hybridize with a sequence-unknown DNA sample. Only the complementary sequence (cDNA) could form a double-stranded DNA (dsDNA) with the DNA probe labeled with AFC. The anodic peak currents (ipa) of the AFC bound to the dsDNA by differential pulse voltammetry were used for the determination of cDNA. The ipa of AFC was linearly related to the concentration of cDNA sequence between 1.0 x 10(-8) and 6.0 x 10(-6) mol L-1. The detection limit was 2.0 x 10(-9) mol L-1 using 3 sigma (where sigma is the standard deviation of blank solution, n = 11). The probe showed high sensitivity and selectivity. PMID- 11205515 TI - Immunodetection of lactosylated proteins as a useful tool to determine heat treatment in milk samples. AB - This paper reports the optimisation of a competitive immunoassay (ELISA) to detect lactosylated proteins in milk samples. The assay employs monoclonal antibodies for lactosylated proteins produced in our laboratory and requires no pre-treatment of the samples other than a dilution step. Monoclonal antibodies were fully characterised in terms of selectivity and cross-reactivity with structurally related molecules and used in a competitive assay format with lactosylated standard proteins (lactosylated ovalbumin). The detection limit for lactosylated ovalbumin was 0.015 microgram ml-1 and the working range was from 0.010 to 40 micrograms ml-1. The data obtained indicate that the ELISA developed is applicable to diluted milk samples and is able to distinguish between milk samples that have undergone different heat treatments (UHT and pasteurised milk). PMID- 11205516 TI - The preparation of a series of nitrostilbene ester compounds using micro reactor technology. AB - The synthesis of stilbene esters using Wittig chemistry has been used to illustrate the generic diversity micro reactors offer in terms of chemical control and rapid method development. The micro reactor consisted of a 'T' design based on channel geometries 200 microns wide and 100 microns deep, etched into borosilicate glass and sealed with a borosilicate top plate using a thermal bonding technique. The movement of the reagent and products was achieved using electroosmotic flow (EOF), assisted by the incorporation of micro porous silica frits within the micro-channels to allow accurate solution control. To optimise the operating conditions methyl 4-formylbenzoate, premixed with sodium methoxide, was reacted with 2-nitrobenzyl-triphenylphosphonium bromide in dry degassed MeOH using flow conditions for both reagents of 0.40 microL min-1 for 20 min. A product yield of 70% (2:1 reaction stoichiometry with the aldehyde in excess) was obtained representing a 10% increase compared with the traditional batch synthesis. To demonstrate the capability of micro reactors to perform atom efficient synthesis a series of experiments based on an injection methodology (optimised to 30 s) were performed in the micro reactor at 1:1 stoichiometry resulting in a yield of 59%. Finally, the capability of micro reactors to perform a series of analogue reactions was investigated. The yields for a further three aldehydes indicated that the technology will be suitable for the development of automated device to support the generation of combinatorial libraries and rapid high throughput synthetic methods. PMID- 11205517 TI - High sensitivity microgravimetric biosensor for qualitative and quantitative diagnostic detection of polychlorinated dibenzo-p-dioxins. AB - A piezoelectric immunosensor system was developed for the rapid detection of polychlorinated dibenzo-p-dioxins (PCDDs). The system uses a competitive inhibition enzyme immunoassay (EIA) based on a mouse monoclonal antibody that is specific for 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and a conjugate of a dioxin-like competitor coupled to the enzyme horseradish peroxidase (HRP). The anti-dioxin antibody was deposited on a 10 MHz AT-cut quartz crystal resonator modified with a self-assembly monolayer of dithiobis-N-succinimidyl propionate. PCDDs at different concentrations in the range 0.001-10 ng mL-1 were mixed with a constant amount of HRP-conjugated competitor. The frequency responses due to the adsorption of the mixed samples on the biosensor surface were measured. The results show that 2,3,7,8-TCDD can be quantitatively detected with the developed immunosensor in the concentration range 0.01-1.3 ng mL-1. Cross-reactivities of the biosensor to various PCDD congeners were also investigated. The sensitivity and selectivity of the quartz crystal microbalance (QCM) biosensor is comparable to EIA and ELISA methods in the detection of polychlorinated dibenzo-p-dioxins. The developed QCM immunosensing system offers significant improvements in speed, sample throughout and cost for the qualitative and quantitative detection of PCDDs compared with GC-MS. PMID- 11205518 TI - Flow injection potentiometric determination of pipazethate hydrochloride. AB - New plastic membrane electrodes for pipazethate hydrochloride based on pipazethatium phosphotungstate, pipazethatium phosphomolybdate and a mixture of the two were prepared. The electrodes were fully characterized in terms of composition, life span, pH and temperature and were then applied to the potentiometric determination of the pipazethate ion in its pure state and pharmaceutical preparations under batch and flow injection conditions. The selectivity of the electrodes towards many inorganic cations, sugars and amino acids was also tested. PMID- 11205519 TI - Electrochemical titrations of thiosulfate, sulfite, dichromate and permanganate using dual microband electrodes. AB - Applications of titration using dual gold microband electrodes in generator collector mode are presented. The main advantage is that the method dispenses with the need for accurate volume measurements and reagent preparation: rather than balancing of molar amounts, the fluxes of analyte and titrant are balanced instead. The titrant is generated electrochemically and the end-point is detected amperometrically by the appearance of a current due to the presence of the titrant at the other band. The aim is to show the versatility and capability of the method that employs disposable mass-produced electrodes and uses pulsed motion of the electrode before a measurement to renew the boundary conditions. The titration of ascorbic acid (vitamin C) with ferricyanide, which has been a model system, was extended to the determination of thiosulfate and sulfite with iodine and the determination of dichromate and permanganate with iron(II). The accuracy, limited by the present fabrication reproducibility of the disposable electrodes, is +/- 10%. The results demonstrate that the method is effective even with a very simple set-up, and the actual time needed for common titrations is significantly decreased. These examples demonstrate a comprehensive basis for further development and applications, including standard titrations in industry. PMID- 11205520 TI - Multivariate data analysis of quality parameters in drinking water. AB - The quality of water destined for human consumption has been treated as a multivariate property. Since most of the quality parameters are obtained by applying analytical methods, the routine analytical laboratory (responsible for the accuracy of analytical data) has been treated as a process system for water quality estimation. Multivariate tools, based on principal component analysis (PCA) and partial least squares (PLS) regression, are used in the present paper to: (i) study the main factors of the latent data structure and (ii) characterize the water samples and the analytical methods in terms of multivariate quality control (MQC). Such tools could warn of both possible health risks related to anomalous sample composition and failures in the analytical methods. PMID- 11205521 TI - Characterization of Galician (N.W. Spain) quality brand potatoes: a comparison study of several pattern recognition techniques. AB - Authenticity is an important food quality criterion and rapid methods to guarantee it are widely demanded by food producers, processors, consumers and regulatory bodies. The objective of this work was to develop a classification system in order to confirm the authenticity of Galician potatoes with a Certified Brand of Origin and Quality (CBOQ) 'Denominacion Especifica: Patata de Galicia' and to differentiate them from other potatoes that did not have this CBOQ. Ten selected metals were determined by atomic spectroscopy in 102 potato samples which were divided into two categories: CBOQ and non-CBOQ potatoes. Multivariate chemometric techniques, such as cluster analysis and principal component analysis, were applied to perform a preliminary study of the data structure. Four supervised pattern recognition procedures [including linear discriminant analysis (LDA), K-nearest neighbours (KNN), soft independent modelling of class analogy (SIMCA) and multilayer feed-forward neural networks (MLF-ANN)] were used to classify samples into the two categories considered on the basis of the chemical data. Results for LDA, KNN and MLF-ANN are acceptable for the non-CBOQ class, whereas SIMCA showed better recognition and prediction abilities for the CBOQ class. A more sophisticated neural network approach performed by the combination of the self-organizing with adaptive neighbourhood network (SOAN) and MLF network was employed to optimize the classification. Using this combined method, excellent performance in terms of classification and prediction abilities was obtained for the two categories with a success rate ranging from 98 to 100%. The metal profiles provided sufficient information to enable classification rules to be developed for identifying potatoes according to their origin brand based on SOAN-MLF neural networks. PMID- 11205522 TI - A help or a hindrance? The impact of job training on the employment status of disadvantaged women. AB - The objective of this study is to evaluate whether welfare-sponsored, government funded job training helps participants improve their employment status. The negligible effects found in prior studies may be due to design limitations or inherent flaws in job training programs and therefore do not necessarily contradict human capital theory. The present study uses longitudinal and representative data, dynamic modeling techniques, an appropriate counterfactual, and important contextual variables to assess the likelihood of obtaining employment for job training participants and nonparticipants. It also describes the types of jobs women obtain by examining wages, industry, occupation, and labor union membership. Whereas some of the results support prior research, the focus is on the unique contributions of this study, which include a differential training effect for full- and part-time workers and a detailed analysis of macro structural variables, which are rarely included in studies of labor supply. PMID- 11205523 TI - Statistical power for nonequivalent pretest-posttest designs. The impact of change-score versus ANCOVA models. AB - Nonequivalent controlled pretest-posttest designs are central to evaluation science, yet no practical and unified approach for estimating power in the two most widely used analytic approaches to these designs exists. This article fills the gap by presenting and comparing useful, unified power formulas for ANCOVA and change-score analyses, indicating the implications of each on sample-size requirements. The authors close with practical recommendations for evaluators. Mathematical details and a simple spreadsheet approach are included in appendices. PMID- 11205524 TI - The Community Readiness Survey. Development and initial validation. AB - This article reports on the development and evaluation of a mail survey measuring population attitudes toward substance use of potential receptivity of communities to different prevention efforts. The Community Readiness Survey was designed through a series of prevention practitioner and consultant meetings and focus groups. Psychometric evaluation revealed five distinct domains: perception of alcohol, tobacco, or other drug problem; support for prevention; permissive attitudes toward teen substance use; perception of adolescent access; and perception of community commitment. Evidence of construct validity was demonstrated by the small but significant relationships between selected scale scores and community readiness as evaluated by prevention planners. PMID- 11205525 TI - Middle school reform through data and dialogue. Collaborative evaluation with 17 leadership teams. AB - This report describes a 2-year, longitudinal study of one school district's effort to link site-based, collaborative evaluation with formal, centralized program evaluation. Participants formed a research team in partnership with a local university. Team members assisted leadership teams in identifying issues for informal, site-based assessments and then used the information to monitor progress toward established goals. Participants collaborated in designing and conducting informal assessments of student achievement, school climate and safety, discipline, and parent involvement. Leadership teams used these data in developing their school improvement plans. Researchers and administrators used these data to revise the districtwide survey. At the end of the 2-year cycle, analysis of school improvement plans showed that collaborative evaluation is creating a connection between dialogue and data. These 17 middle schools are approaching school improvement in a more integrated fashion by actively involving key stakeholders (students, parents, and teachers) in the evaluation process. PMID- 11205526 TI - Aging and feature search: the effect of search area. AB - The preattentive system involves the rapid parallel processing of visual information in the visual scene so that attention can be directed to meaningful objects and locations in the environment. This study used the feature search methodology to examine whether there are aging-related deficits in parallel processing capabilities when older adults are required to visually search a large area of the visual field. Like young subjects, older subjects displayed flat, near-zero slopes for the Reaction Time x Set Size function when searching over a broad area (30 degrees radius) of the visual field, implying parallel processing of the visual display. These same older subjects exhibited impairment in another task, also dependent on parallel processing, performed over the same broad field area; this task, called the useful field of view test, has more complex task demands. Results imply that aging-related breakdowns of parallel processing over a large visual field area are not likely to emerge when required responses are simple, there is only one task to perform, and there is no limitation on visual inspection time. PMID- 11205527 TI - The locus of age x health-related physical fitness interactions in serial choice responding as a function of task complexity: central processing or motor function? AB - The extent to which health-related physical fitness (HRF) attenuates age differences in psychomotor speed as a function of task complexity was examined in a sample of 48 men. Physiological measures were used to assign participants to fitness group (n1-4- = 12): young less fit (mean age = 25.83 years), young fitter (mean age = 25.08 years), old less fit (mean age = 71.83 years), old fitter (mean age = 66.75 years). A serial choice reaction time (RT) task was used in which three conditions of two, four, or eight choices were administered. RTs for the choice and motor components of the task were recorded separately. A significant Age x HRF interaction was found in relation to choice RT but not motor time; older less fit individuals underperformed older fitter participants, and younger adults regardless of fitness level. This interaction remained significant having statistically controlled for motor function, suggesting benefits to central processing. The strength of this interaction did not increase as a function of task complexity. The findings suggest an association between HRF and psychomotor speed, and support the view that physically active lifestyles should be encouraged among older adults. PMID- 11205528 TI - Overall vigilance and sustained attention decrements in healthy aging. AB - Age differences in sustained attention were investigated using a high-event rate digit-discrimination task at 6 levels of stimulus degradation (lasting 8.1 min each). Twenty-one young, 21 middle-aged, and 20 old healthy subjects were studied. Overall sensitivity (d') was equivalent in all groups. Although all subjects showed a sensitivity decrement over blocks, there were no age-related differences in sustained attention capacity. All subjects had larger decrements in d' over blocks at higher degradation levels. However, the performance decrement at higher degradation levels was equivalent in all groups, indicating similar decrement rates in sensitivity with increasing demands on effortful processing. These results indicate that overall levels of vigilance and the ability to sustain attention over time are equivalent in all groups under conditions requiring both automatic (low-degradation) and effortful (high degradation) stimulus processing. PMID- 11205529 TI - Goal-setting, self-efficacy, and memory performance in older and younger adults. AB - Research in field and laboratory settings has shown that goals lead to improved self-efficacy and performance, especially when individuals also receive positive feedback. The present study extended goal-setting theory to examine self-set goals and feedback in relation to younger and older adults' memory performance and self-efficacy. Following a baseline recall trial, participants completed three shopping list recall trials. Half of the participants were instructed to set goals for the three experimental trials, and half in each goal condition received performance feedback after each trial. Young adults' self-efficacy, clustering, and recall exceeded that of older adults. Goal setting increased self efficacy for younger but not older adults, and it did not affect performance. Younger adults and participants in the feedback condition increased their goals across trials, as did participants for whom feedback indicated success. These data provide a first look at the motivational impact of feedback and self-set recall goals in memory aging. Additional study is needed to understand the interactive effects of type of feedback, memory task difficulty, and type of goal setting at different ages. PMID- 11205530 TI - Perceived work environment and cognitive style. AB - Differences in perceived work environment are examined by age, gender, and occupation type, along with whether cognitive style predicts perceived work environment. The sample consists of 2185 men and women ranging in age from 21 to 93 years. Perceived work environment was measured using Moos's Work Environment Scale (WES) for the subscales of Autonomy, Control, and Innovation. The Test of Behavioral Rigidity (TBR) was used to measure cognitive style. Findings indicate significant mean level differences in perceived work environment based on gender, age, and occupation type. Hierarchical regression analyses indicated that perceived work environment predicted concurrent cognitive style beyond demographic variables. PMID- 11205531 TI - Temporal control of rhythmic performance: a comparison between young and old adults. AB - Young (20-30-year-old) and older (60-76-year-old) adults were tested on two measures of rhythmic performance. The first involved tapping at the subject's own preferred rate, a measure of so-called internal tempo. Over five sessions of testing, tapping rates were consistently and significantly slower on average in the older subjects than the younger ones, but rates were not relatively more variable in older subjects (i.e., coefficients of variation, standard deviation/mean, did not differ between the older and young people). In addition, both old and younger subjects performed on a synchronized-tapping and continuation task of the type used by Wing and Kristofferson (1973, Perception and Psychophysics, 14, 3-12). Target interresponse times were 300, 400, 500, 600, and 700 ms, and in all cases interresponse intervals produced by both the old and young adults matched the target times very closely. Wing and Kristofferson's analytical procedure was used to decompose tapping variance into that attributable to timing processes and that resulting from motor implementation of the timing signal. Both sorts of variance increased with increasing target interresponse time (with timer variance increasing most markedly), but no difference was found in either type of variance in comparisons between the old and younger subjects. If the internal tempo measure directly reflects the speed of internal timing processes, the data suggest that such processes are slower, but not relatively more variable, in older than younger subjects (consistent with some previous evidence and speculation), but that the calibration of performance forced by the synchronization task will make such an age-related difference in "internal clock speed" unobservable on synchronized-tapping tasks. PMID- 11205532 TI - Bioaccumulation of polychlorinated biphenyls (PCBs) and dichlorodiphenylethane (DDE) methyl sulfones in tissues of seal and dolphin morbillivirus epizootic victims. AB - Polychlorinated biphenyl (PCB) and dichlorodiphenylethane (DDE) methyl sulfone (MSF) metabolites possess high affinities for binding two homologous 16,000 Da homodimeric receptor proteins in the lung (Clara cell secretory protein, CCSP) and the uterus (uteroglobin, UG), leading to selective bioaccumulation of MSFs in these tissues. As marine mammals are highly exposed to organochlorines, concentrations of PCBs, PCB MSFs, DDT, and DDE MSF were analyzed in blubber, lung, and uterus samples from harbor seal (Phoca vitulina) and striped dolphin (Stenella coeruleoalba) morbillivirus epizootic victims to investigate uterine and lung MSF accumulation. Mean uterus concentrations of PCB MSFs and DDE MSF in harbor seals were 0.61 and 0.04 microg/g lipid weight and in striped dolphins 0.05 and 0.01 microg/g lipid weight. Mean lung concentrations of PCB MSFs and DDE MSF in harbor seals were 0.96 and 0.02 microg/g lipid weight and in striped dolphins 0.16 and 0.01 microg/g lipid weight. To ascertain whether uterine and lung bioaccumulation of MSFs is possible due to the presence of CCSP and UG in seals, CCSP and UG proteins in uterine flushings and in uterine and lung and epithelial tissue from Baltic gray and ringed seals were characterized using gel electrophoresis and Western blotting techniques. UG- and CCSP-like proteins with molecular weights of 16,000 Da were resolved in all samples. This is the first demonstration of this protein in any marine mammalian species. The toxicological implications of MSF binding with UG and CCSP in marine mammals are discussed. PMID- 11205533 TI - Chrysotile asbestos fibers detected in the newborn pups following gavage feeding of pregnant mice. AB - Female pregnant mice were fed chrysotile asbestos suspension by gavage to determine whether there is transfer of fibers to the fetuses. Groups of mice were given 2 doses of either 50 microg chrysotile suspension in 0.2 ml sterile normal saline (treated), or 0.2 ml saline (control), and were allowed to mate 2 d later. After pregnancy was confirmed, the treated and control groups received 2 additional doses of chrysotile asbestos or saline on gestational d 7 and 12. Both groups were allowed to deliver naturally, and the pups were sacrificed at 8, 1, 19, or 20 d after birth. The lungs and liver of two pups from each mother were processed for fiber counts using electron microscopy and energy-dispersive x-ray analysis (EDXA). All pups of the treated group had chrysotile fibers, while none were present in pups from controls. The mean fiber count of the lungs of treated group of pups was 780 fibers/g, and the mean fiber count of the liver was 214 fibers/g. Mean length of the fibers in the lung and liver was 18.48 microm and 18.30 microm, respectively. The fibers were thin, measuring 0.42 microm and 0.33 microm in the lung and liver, respectively. There was no significant difference in the weight gain between the treated and control group of pups. The postnatal fetal mortality of the 2 groups, 8.2% for the treated and 4.5% for the control group, were not statistically significant. To our knowledge, this is the first animal study to demonstrate that oral ingestion of chrysotile asbestos during pregnancy results in transfer of asbestos fibers to the fetuses. PMID- 11205534 TI - Effects of diquat, an aquatic herbicide, on the development of mallard embryos. AB - Bipyridylium herbicides produce embryotoxic and teratogenic effects in dipteran, amphibian, avian, and mammalian organisms. Diquat dibromide, a bipyridylium compound, is commonly used as an aquatic herbicide. Mallard (Anas platyrhynchos) eggs were exposed to diquat by immersing the eggs for 10 s in solutions of 0.88, 3.5, 7, 14, or 56 g/L on either d 4 or 21 of incubation. Application of diquat on d 4 yielded an estimated LC50 of 19.5 g/L through 18 d of incubation, and 9.6 g/L through hatching. Body and organ weights, and bone lengths of hatchlings did not differ between control and treatment groups with the exception of a slight increase in brain weight in the 14 g/L group. Malformations in diquat-treated embryos included defects of the brain, eye, bill, limb, and pelvis; skeletal scoliosis; and incomplete ossification. Subcutaneous edema was also present. Significant manifestations of oxidative stress were apparent in hatchlings and included increased hepatic thiobarbituric acid-reactive substances (TBARS) (lipid peroxidation) and decreased brain reduced glutathione (GSH). Brain protein-bound sulfhydryls (PBSH) increased. Diquat applied on d 21 of incubation yielded an estimated LC50 of 12.6 g/L through hatching. Exposure at this late stage of development did not produce deformities. Body and organ weights and, bone lengths of hatchlings did not differ between control and treatment groups. Significant manifestations of oxidative stress in hatchlings included decreased brain GSH, increased oxidized glutathione (GSSG), and ratio of GSSG to GSH. This study suggests that concentrations of diquat commonly used for aquatic weed control, when based upon the dilution effect of average water depth of the application area, would probably have little impact on mallard embryos. However, concentrations applied above ground to weeds and cattails along ditches could adversely affect the survival and development of mallard embryos, and presumably other avian species nesting in such habitats. PMID- 11205535 TI - Lipid peroxidation in rat adrenal glands after administration cadmium and role of essential metals. AB - The aim of this study was to investigate the effects of cadmium-induced peroxidative damage to rat adrenals. Cadmium significantly increased adrenal lipid peroxidation in a dose- and time-related manner. Cadmium-induced lipid peroxidation was accompanied by a marked elevation in adrenal iron (Fe) levels, in particular the free elemental form. Chelation of Fe with deferoxamine decreased the cadmium effect on lipid peroxidation. Selenium (Se) was also effective in inhibiting Cd-induced adrenal lipid peroxidation. Data indicate that Cd-induced lipid peroxidation in rat adrenals may be dependent upon Fe and Se levels in this tissue. PMID- 11205536 TI - Bioindication of heavy metals with aquatic macrophytes: the case of a stream polluted with power plant sewages in Poland. AB - The Kozi Brod (left tributary of the Biala Przemsza, east of Katowice) flows in a highly industrial coal-mining area dominated by the power plant of Siersza. Concentrations of the microelements nickel (Ni), chromium (Cr), cobalt (Co), zinc (Zn), manganese (Mn), lead (Pb), cadmium (Cd), copper (Cu), barium (Ba), aluminum (Al), vanadium (V), and strontium (Sr), as well as the macronutrients nitrogen (N), phosphorus (P), potassium (K), calcium (Ca), magnesium (Mg), iron (Fe), and sulfur (S), were measured in water and plants of the Kozi Brod. The collected plants were: Myosotis palustris L. Nathorst, Galium palustre L., Mentha rotundifolia L. Huds., Mentha aquatica L., Berula erecta (Huds.) Coville, Cardamine amara L., Epilobium angustifolium L., Geranium palustre L., Lysimachia vulgaris L., Crepis paludosa L. Much., Calitriche verna L., Solanum dulcamara L., and the aquatic moss Hygrohypnum ochraceum (Turn.) Loesk. These plants were used to evaluate the spatial distribution of elements in the Kozi Brod and contained elevated levels of Co, Cd, Zn, Ni, Mn, Al, Pb, and Cu. Significant correlations between concentrations of Cd, Zn, and Mn in water and plants indicate the potential of these species for pollution monitoring. PMID- 11205537 TI - Pulmonary responses to single versus multiple intratracheal instillations of silica in rats. AB - The pulmonary toxicity of particles is often studied using a single intratracheal instillation of the material. It was hypothesized that smaller multiple intratracheal administrations of silica would result in differences in pulmonary responses as compared to a single large intratracheal administration. In the first of a series of experiments, the pulmonary responses in male F344 rats to a single intratracheal instillation of crystalline silica (5 mg/100 g body weight) given on d 0 were compared with those resulting from 5 consecutive daily intratracheal administrations of the dust (1 mg/100 g body weight/d) with the initial dose given on d 0. Controls received saline intratracheally. In the second experiment, the dose was reduced to 1 mg/100 g body weight for the single dose protocol and 0.2 mg/100 g body weight/d for 5 consecutive days for the multiple-dose protocol. In both experiments, responses were assessed on d 14. In the third experiment, the doses were the same as the first experiment, but the responses were assessed on d 28. The indices of toxicity were cellular differentials recovered by bronchoalveolar lavage, which is an index of inflammation, and the level of albumin in the bronchoalveolar lavage fluid, a measure of damage to the capillary-epithelial barrier. At the higher dose of silica, similar levels of inflammation and lung damage were evident in both dosing protocols. Less severe responses occurred at the lower dose. The comparative pattern between the single and multiple dosing protocols was similar in all three experiments. Since only minor differences were noted in the pulmonary responses when the responses to the single- and multiple-dose protocols were compared, data indicate that the multiple-dose protocol does not offer any advantages over the single-dose protocol. PMID- 11205538 TI - [Prevalence of multiple sclerosis in Colombia]. AB - INTRODUCTION: Multiple sclerosis (MS) is the commonest demyelinating condition of the nervous system. It is characterized by numerous demyelinating areas or plaques of demyelination which are found dispersed throughout the nervous system. It has been shown that MS is less frequent in tropical regions than in subtropical regions. In Latin America particularly, there are some studies which show this phenomenon. However, in Colombia no studies of prevalence of MS have been done. OBJECTIVE: To determine the prevalence of multiple sclerosis in five provinces of Colombia (Antioquia, Caldas, Santander, Risaralda and Bolivar). PATIENTS AND METHODS: The capture-recapture method was used for two sources to determine the number of cases defined on the criteria of Poser et al seen between July 1995 and June 2000. RESULTS: The prevalence (cases of MS per 100,000 inhabitants) varied between 1.48 in Antioquia (95% CI 1.12; 1.78) and 4.98 in Risaralda (95% CI 3.52; 6.43). Seventy two percent were women. The regions included in this study represented 25% of the population of Colombia. CONCLUSIONS: There is a low prevalence of MS which is as expected in tropical areas. Persons with MS in these regions may be very useful in the study of other factors involved in the aetiology of MS (genetic). The capture-recapture method is an excellent tool for carrying out prevalence studies since it is cheap and requires little time. PMID- 11205539 TI - [Visual field changes secondary to vigabatrin treatment]. AB - INTRODUCTION: Vigabatrin is an effective antiepileptic drug for treatment of partial crises with or without generalization. It acts by increasing GABA levels by irreversible inhibition of the enzyme GABA-transaminase. In recent years there have been several reports published on the appearance of alterations of the visual fields of patients treated with this drug. OBJECTIVE: To study the prevalence and characteristics of the visual field changes associated with vigabatrin treatment in an adult epilepsy clinic. PATIENTS AND METHODS: Ophthalmological examination, consisting of questions about eye symptoms, study of the fundus oculi, Humphrey-type campimetry, protocol 30-2, visual evoked potentials and electroretinogram were done on a group of 10 patients on long-term vigabatrin treatment. RESULTS: Six of the ten patients (60%) had campimetric alterations, which were serious in two cases (20%). Only the two patients with severe field defects complained of sight changes when questioned and their complaints were mainly of repeatedly bumping into things. In two patients (20%) there was pallor of the optic nerve. In both cases, the patients with severe field defects showed alterations on the electroretinogram. Visual evoked potentials were normal in all cases. CONCLUSIONS: There is a very high prevalence of visual field defects in patients on long-term treatment with vigabatrin. Clinical ophthalmological signs are not usually seen until advanced stages. Pallor of the optic nerve was seen in a group of patients. It is very important that serial campimetric studies are done for early detection of such alterations. PMID- 11205540 TI - [Parkinson's disease, side affected and depression]. AB - INTRODUCTION: Depression is a state of mind often associated with Parkinson's disease, which is not correlated with the stage of the disease or the response to treatment with L-dopa. It has been suggested that patients with right-sided Parkinsonism have more depression than those with left-sided. OBJECTIVE: To assess whether patients whose dominant side is affected primarily have more depression than those whose non-dominant side is affected; and to evaluate whether when the dominant side is more affected this is accompanied by greater deterioration on the scale of everyday activities (ADLS) and on the motor part of the unified scale for evaluation of Parkinsonism (UPDRSm). PATIENTS AND METHODS: The study group was formed of 63 patients with Parkinsonism at stage 1 or 1.5 (Hoehn and Yahr), with an average age of 66.17 years. They were divided into two groups. Those who received L-dopa (Dopa group) and those who were newly-diagnosed patients (Naive group). They were evaluated on the Hamilton test, UPDRSm and ADLs scale. We used Wilcoxon's nonparametric sum of ranges test taking p < 0.01 as significant. RESULTS: The indexes of depression were greater, in both groups, in the patients whose dominant side was affected (p < 0.001). There were no differences in UPDRSm or ADLs. CONCLUSIONS: The patients with Parkinson's disease whose dominant side is primarily affected have worse depression. The depression seems originate in the dominant hemisphere. PMID- 11205541 TI - [Factorial structure of the executive functions in young university students]. AB - INTRODUCTION: Several studies have proposed a multiple dimensional theoretical model for executive function. OBJECTIVE: To identify the factor structure of the executive function in a sample of young university students of different modalities of learning in their careers. METHODS: 100 participants of both sexes, age 16 to-21-year old and normal Full Scale IQ were selected in a randomized and representative approach from private universities of Medellin Colombia. They were student of verbal, visuospatial and mathematical careers. A executive function assessment battery were applied, which included: Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT) A and B, verbal fluency test (FAS) by phonologic and semantic guides, and Stroop test. RESULTS: A structure of four factor was found, which explained 74.9% of variance. Factors were: 1. Organization and flexibility, which explained 26.6% of variance; 2. Processing speed, 19.7%; 3. Inhibitory control, 15.1%; and 4. Verbal fluency 13.4%. CONCLUSION: A multiple factor structure of the executive function in young university students was demonstrated. PMID- 11205542 TI - [Cerebellar hematomas: a surgically treatable stroke]. AB - INTRODUCTION: Spontaneous cerebellar hematomas make up nearly 10% of the intracranial intraparenchymatous hemorrhages. In recent years several algorithms have been published for the management of these patients. OBJECTIVE: To study the type of treatment, conservative or operative, and the main prognostic factors. PATIENTS AND METHODS: We present a retrospective analysis of 52 cases of spontaneous cerebellar hematomas diagnosed over the past 10 years in the Hospital General de Galicia. We studied the clinical and radiological factors with the greatest effect on prognosis and the approach to treatment. RESULTS: We found a male/female ration of 2/3. The age of 90.3% of our patients was over 60 years. Arterial hypertension had previously been diagnosed in 55.7% of the cases. The clinical picture was characterized by the profile of a stroke with headache (90.3%), vomiting (63.4%) and impaired consciousness (50%) being the commonest presenting symptoms. The most important factors in prognosis were the level of consciousness and the size of the hematoma. The prognosis was worse in cases with hydrocephalus, intraventricular hemorrhage or extension of the hematoma towards the midline. Neither age, sex nor the previous diagnosis of arterial hypertension were of importance in prognosis. Mortality was 25%. CONCLUSIONS: The spontaneous cerebellar hematomas typically affect patients over the age of 60 years and present with headache and vomiting of sudden onset. In our series the major prognostic factors were the size of the hematoma and level of consciousness, and treatment was given in accordance with this. PMID- 11205543 TI - [Medium and large acoustic neurinomas with normal tonal audiometry at the moment of diagnosis]. AB - INTRODUCTION: Early diagnosis of an acoustic neurinoma for any possible treatment is important, especially in view of the relationship between surgical morbidity and the size of the tumour. The commonest presenting symptom of these tumors is unilateral perceptive deafness. However, between 4 and 12% are diagnosed before deafness occurs, although they may be large in size. Therefore one should remember other symptoms which lead to suspicion of these tumors, and have diagnostic guidelines available to allow the earliest possible detection. PATIENTS AND METHODS: We report four cases of acoustic neurinoma or vestibular schwannoma of medium or large size in which audiological studies did not at first give rise to suspicion of the presence of this tumour, since audition was considered to be normal at conversation frequencies (500 to 3,000 Hertz) for the age of the patient or who had an audiometry curve with symmetrical deafness in both ears. CONCLUSION: We evaluated the diagnostic importance of the tests done and compared the results with data published in the literature. PMID- 11205544 TI - [Multiband spectral analysis and standardized markers of the slope of pediatric electroencephalograms]. AB - INTRODUCTION: The infantile electroencephalogram has been studied in connection with many cognitive disabilities. Although normal resting infantile bioelectric recordings are known, the cortical distribution of electroencephalographic frequencies during other sensory and/or cognitive mental processes is less well known. OBJECTIVE: Our interest is based on the description of EEGs of a homogeneous sample of healthy children and their relation to intellectual activities. MATERIAL AND METHODS: The sample studied was made up of 13 healthy children with an average age of 9.3 +/- 1.3 years, on whom two types of tests of attention were done. One of the tasks was a simple auditory memory test and consisted of the spoken repetition of a series of numbers previously heard, which was of variable length. The second test consisted of the identification and crossing out of one face of a series of three faces, which included one which was different from the others. The methodology chosen was electroencephalographic measurement in the frequency and temporal domains. RESULTS AND CONCLUSIONS: There was a relative increase in beta frequencies in all cortical sites which was significant in T3 and T4 with the auditory test and in all electrodes with the visual test. During auditory testing reduction in the alpha frequency was observed in frontotemporal regions. The greatest cortical variations of beta frequency occurred, in the facial test, in the electrodes O2, T6, O1, T5 and T3. The values of Hjorth complexity obtained varied within the interval 1 to 3, which was a considerably lower interval than that found in adult populations. PMID- 11205545 TI - [Our experience with the programmable Codman-Medos valve: review of 125 shunts]. AB - INTRODUCTION: Programmable valves are a possible solution in cases of excessive or insufficient draining. OBJECTIVE: To report our experience with these shunts and clarify concepts. PATIENTS AND METHODS: We have implanted 125 Codman-Medos programmable devices in 118 patients. The most frequent indication was secondary hydrocephalus, particularly due to obstruction by a tumour, and primary hydrocephalus. They were also used in cases of benign intracranial hypertension, CSF fistulas and arachnoid cysts. Most valves were inserted frontally, under antibiotic prophylaxis. RESULTS: Excluding patients with a follow-up of less than three months, the average follow-up was 14.63 +/- 9.07 months, with clinical improvement in 80%. There was 0% mortality in relation to surgery. The initial average pressure was 121.84 +/- 24.74 mmH2O and after 52 reprogrammings done in 36 (30%) of the patients, the final average pressure was 124.96 +/- 30.58 mmH2O. Reprogramming was done for the management of symptoms and to avoid subdural hygromas. We have observed no clinical signs of unprogramming. There were 29 complications which were treated by reprogramming in 7 cases and surgically in the remainder. CONCLUSIONS: We recommend frontal insertion, with a long peritoneal catheter, mainly in patients with hydrocephalus secondary to stenosis of the aqueduct of Sylvius, benign intracranial hypertension, after head injury and Arnold-Chiari malformation. The initial pressure is difficult to determine but tends to be average or high. Reprogramming is particularly useful in the treatment of subdural hygromas. We have observed no clinical signs of unprogramming. Complications tend to be due to surgical technique rather than the particular shunt used. PMID- 11205546 TI - [Early assessment in perinatal hypoxia. Prognostic markers]. AB - INTRODUCTION: Perinatal asphyxia and its neurological signs are the most important cause of brain damage and neurological sequelae in full term newborn babies. Neuroprotection treatments currently being investigated promise to reduce such sequelae, but these treatments are not without risk and the patients involved should be selected. OBJECTIVE: To analyze a scale composed of variables recorded from the start of delivery until the fourth hour of life, comparing the neurological evolution of the patients. By means of this scale we aim to establish a criterion for the selection of neonates with acute perinatal asphyxia, who would benefit from neuroprotector treatment. PATIENTS AND METHODS: A retrospective study was made of 50 patients with the diagnosis of perinatal asphyxia. Our scale was formed of the following variables: intrauterine meconiorrhexis, pathological cardiotocographic recordings, resuscitation at birth, Apgar score at five minutes, pH of the umbilical artery blood, neurological examination, multisystemic involvement, seizures, persistent metabolic acidosis and need for mechanical ventilation during the first hours of life. The patients were followed up for at least one year by means of periodical studies (neurological examination and evaluation of psychomotor development according to the Brunnet Lezinne test). For statistical analysis we used the chi squared test, Fisher's exact test, Kruskal-Wallis test and the area beneath the ROC curve. RESULTS AND CONCLUSIONS: The scale presented constitutes a rapid, easy method which is statistically significant for the selection of perinatal asphyxia of high neurological risk which would benefit from neuroprotector treatment after the event. PMID- 11205547 TI - [Falling backward: atypical sign of iodiopathic Parkison's disease. Use of intravenous apomorphine as a diagnostic test]. AB - INTRODUCTION: The differential diagnosis of a parkinsonian syndrome is extensive and complex. In most cases, however, a detailed clinical examination will help to differentiate between idiopathic Parkinson's disease (IPD) and other causes of parkinsonism. PATIENTS AND METHODS: 10 patients with an average age of 65.1 years (range 60-70), of whom 6 were men and 4 women were referred to our department with a diagnosis of IPD and history of backwards falls. The average duration of disease was 4.7 years (range 4-7). All 10 patients had at presentation a severe akinetic-rigid syndrome with no other symptoms of IPD. I.v. apomorphine (APO) was administered to each of them at a rate of 8.9 mg/hr (range 15.3 mg/hr) for an average time of 5.4 hours (range: 3-10 hours). RESULTS: The improvement of the akinetic-rigid state in six of the patients during the i.v. infusion with APO helped to elicit signs that are atypical of IPD (ataxia and postural instability). Three of the patients did not respond to i.v. APO and one of them could not be evaluated, as he did not tolerate the infusion. Oral Dopa challenge or s/c APO bolus has not been as successful in helping to differentiate IPD from other parkinsonian syndromes. CONCLUSIONS: The prompt detection of postural instability or retropopulsion is necessary in order to diagnose atypical parkinsonian syndromes. In difficult cases, continuous i.v. APO will improve the akinetic-rigid state and facilitate the detection of atypical signs. The pharmacokinetic characteristics of APO, and the advantage of it being possible to administer the drug i.v. in a few hours increases the viability of this test. PMID- 11205548 TI - [Value of the MSH classification in the hemiplegic stroke patient]. AB - INTRODUCTION: The functional prognosis of patients should be known when planning their rehabilitation treatment. OBJECTIVE: To find the prognostic value of the MSH classification for hemiplegic patients, which is based on the clinical deficits seen after the stroke, and to distinguish between the M group (motor deficit), MS group (motor and sensory deficits) and the MSH group (motor, sensory and homonymous deficits). PATIENTS AND METHODS: A prospective analytical study was made of the hemiplegic patients admitted consecutively to the Rehabilitation Department after strokes. The initial examination was made 17 days (CI: 15-19) after the stroke. Satisfactory functional results were considered to be obtaining a Barthel index of > 90 together with the ability to walk unaided on level ground six months after the stroke. RESULTS: Of the 55 patients finally included in the study, 23 were in group M (41.8%) 21 in group MS (38.1%) and 11 patients in group MSH (20.1%). Walking ability and function in the different cohorts showed a statistically significant difference. Whilst 96% of the patients with pure hemiparesia (group M) attained a satisfactory degree of independence in walking, only 54% of the patients with three associated deficits (MSH) achieved this. Even more difference was found with acquired functional independence, since whilst 82% of group M attained a good degree of autonomy in carrying out everyday activities, only 18% of the MSH group achieved this. The remaining patients (MS group) had intermediate results. CONCLUSION: The MSH classification is, soon after having a stroke, a useful means of determining the functional prognosis of hemiplegic patients. PMID- 11205549 TI - [Cardioembolic infarction: clinical course and characteristics]. AB - INTRODUCTION: Approximately 20% of all ischemic strokes are due to cardioembolism and occur more frequently in the younger patients. Our objective was to determine the clinical characteristics and course of cardioembolic infarcts (ICCE) comparing them with infarcts due to other aetiologies (ICNCE). PATIENTS AND METHODS: We made a prospective study of 354 patients admitted to hospital over a period of one year, after excluding transient ischaemia and parenchymatous/subarachnoid hemorrhage. Two groups were established: ICCE (29.4%) and ICNCE (70.6%), comparing age, sex, risk factors and course of the illness. Subsequently a study lasing two years was done to assess the recurrence rate. RESULTS: The ICCE patients were older (75.89 compared with 72.58, p = 0.004), often know the exact time of onset of their symptoms (p = 0.015) and usually are admitted to hospital during the first six hours of their illness (p = 0.01). There was a significantly higher incidence of ischemic cardiopathy or auricular fibrillation (p = 0.0052); p = 0.005); more complications arose (p = 0.000); stay in hospital was longer (13.62 as compared to 11.8 days; p = 0.035), there was a lower weekly BI score (p = 0.0023) and higher mortality (p = 0.000). In the subgroup of 70 patients evaluated two years later 11 cases recurred, with no difference observed between the anticoagulant and anti-aggregant groups. CONCLUSION: The ICCE occurs in older patients, they develop worse neurological defects, have a worse short-term prognosis, develop more complications and have significantly greater mortality. PMID- 11205550 TI - [Electro-clinical concordance for childhood absence epilepsy in monozygotic twins]. AB - INTRODUCTION AND OBJECTIVE: The objective of the study was to analyze the EEG tracings during the seizures of two monozygotic twins, shown on molecular analysis, diagnosed as having infantile epilepsy with absences. The recordings are particularly interesting since the genotypes of the patients are identical. This allowed comparison between the similarities and differences in discharges so that they could be better defined. RESULTS: The 3 Hz spike and wave complexes were the same as the classical descriptions in typical absences. No 'W' spike and wave complexes morphology, discharge fragmentation or light induction of the discharges were observed. There was some differences in the duration of absences, which were much shorter in one twin girl. The duration of the seizures was variable, and sometimes similar to that described as characteristic in other types of generalized idiopathic epilepsies with absences. It would seem therefore that the duration of the seizure is not a criterion for differentiation between the different types of generalized idiopathic epilepsies. CONCLUSION: Concordance, both clinical and of seizure EEG recordings in our patients confirmed that there is a specific electroclinical phenotype in infantile epilepsy with absences, although individual variations may also occur. PMID- 11205551 TI - [Lyell syndrome associated with lamotrigine]. AB - INTRODUCTION: Lamotrigine (LTG) is a new antiepileptic of habitual use in monotherapy as much in partial epileptic as in generalised, which presents among other adverse effects: slight rashes and less frequently severe rashes such as Stevens-Johnson syndrome and Lyell syndrome or toxic epidermal necrolysis, above all in combination with valproate (VPA). CLINICAL CASE: A 44-yr-old woman in toxico-alcoholic epileptic treatment with VPA, showed a neutropenia possibly of secondary type which it was intended to change to LTG, following an ascending dose of LTG joined to a descending dose of VPA. In the sixth treatment week, the patient developed an erythematous rash which after a week of solar exposure, presented temperature, general discomfort, and in the head, on the front and back part of the thoracic and upper and lower limbs, erythematous lesions with scabbed areas, loosening epidermis areas with a positive Nikolsky sign and severe mucous membrane involvement, being diagnostic of Lyell syndrome. The lesions got slowly better with serum therapy, antibiotherapy, parenteral corticoids and topical treatments. CONCLUSIONS: There is a probability of severe rash associated with lamotrigine which has to be taken into account, and we advise patients to suppress the medication when they present a minimum rash. PMID- 11205552 TI - [Fluctuation in bilateral thalamic infarction: diffusion study using magnetic resonance]. AB - INTRODUCTION: Bilateral paramedian thalamic infarcts are uncommon. The most frequent clinical manifestations are acute impairment of consciousness, oculomotor abnormalities and cognitive disturbances. A fluctuating course has not been previously reported. CLINICAL CASE: A 66 year-old woman with a past history of arterial hypertension and diabetes was admitted to our hospital presenting four episodes of decreased consciousness and vertical gaze paresis. Neurological examination between episodes was unremarkable. Diffusion-weighted magnetic resonance imaging revealed high-signal lesions in both paramedian thalamic areas. CONCLUSIONS: Fluctuating impairment of consciousness may be a clinical presentation of bilateral paramedian thalamic infarction. Atheromatous occlusion of the mouth of the paramedian thalamic penetrating artery is the most common cause. Neurological findings and diffusion-weighted images may help to define the extension and the underlying pathophysiological mechanism. PMID- 11205553 TI - [Backache as the initial symptom of adrenomyeloneuropathy]. AB - INTRODUCTION: Adrenoleukodystrophy is a paroxysmal disorder, with recessive linking to the X chromosome, characterized biochemically by the accumulation of extra-long-chain fatty acids. Six phenotypes are distinguished: pre-symptomatic, infantile, adolescent and adult cerebral forms, adrenomyeloneuropathy and isolated Addison's disease. We describe a patient with adrenomyeloneuropathy in whom the presenting symptom was lumbago. CLINICAL CASE: A 23 year old man with no significant previous clinical history complained of having lumbago for over two years. On examination he had pyramidal signs and reduced epicritic sensitivity of the legs. Laboratory investigations showed adrenal failure, increased plasma extra-long-chain fatty acids concentration, mononuclear cells and fibroblasts. On MR there was a hyperintense lesion of the genu of the corpus callosum. SSEP were pathological while the electroneurogram showed bilateral increase in latency of the F wave. The patient was diagnosed as having adrenomyeloneuropathy and treatment started with hydrocortisone, a diet low in extra-long-chain fatty acids and 'Lorenzo's oil'. The lumbago gradually disappeared while the plasma extra long-chain fatty acids concentration dropped. The oil was stopped because of moderate thrombocytopenia, and treatment was started with lovastatin 40 mg/day. Two years later the patient has no lumbago and is neurologically stable. CONCLUSIONS: The lumbago associated with adrenomyeloneuropathy is probably due to demyelination of the spinal tracts. Although lumbago is usually a benign condition, a careful history and examination is necessary in all such cases. PMID- 11205554 TI - [Review of Creutzfeldt-Jakob disease and other prion diseases]. AB - INTRODUCTION: Creutzfeldt-Jakob disease (CJD) is a rapidly progressive dementia syndrome which is probably caused by prions. The annual incidence of this disease is 1/1,000,000. Most cases are sporadic in type, although 10-15% are familial. The total incidence of CJD has not changed following the epidemic due to a new variant (nv-CJD); however, this has led to greater awareness of the subject. OBJECTIVE: To review current scientific knowledge of CJD. DEVELOPMENT: A search was made for relevant literature using MEDLINE. The criteria proposed for diagnosis of CJD include the presence of progressive dementia and at least two of the following characteristics: 1. Myoclonias, 2. Cortical blindness, 3. Pyramidal, extrapyramidal or cerebellar signs, 4. Akinetic mutism, or 5 Abnormal EEG. Laboratory and neuroimaging investigations may also help in diagnosis of CJD, although neuropathological confirmation is necessary for definite diagnosis. Two promising methods of pre mortem diagnosis of CJD are determination of 14-3-3 protein in the cerebrospinal fluid, in the case of sporadic CJD, and biopsy of the palatine tonsil in the case of nv-CJD. The physiopathology of CJD seems to be centred on the proteins forming prions, which are glycoproteins found in the plasmatic membrane and are very often expressed in the neurons, particularly at neuromuscular junctions and synapses. The pathological form resists proteolytic degradation, so that they accumulate in the CNS. The precise neurotoxic mechanism of these proteins is still not clear. CONCLUSIONS: There is still no treatment for CJD. Further studies of the physiopathological mechanisms of prion diseases may help in the development of treatment to delay the progress of this disease. PMID- 11205555 TI - [Classification of the astrocytic gliomas. Brief comments]. AB - INTRODUCTION: Gliomas make up approximately 50% of the primary brain tumors of the central nervous system in adults. Astrocytes from between 70 and 75% of these tumors. Historically grading these has been very controversial, in spite of its importance for prognosis and planning treatment. DEVELOPMENT: We have reviewed existing proposals for the classification of astroglial neoplasias, from the initial studies to the latest classification by the World Health Organization. All have pursued the objective of finding the histopathological grade of the neoplasm to relate it to survival and predict prognosis. CONCLUSION: Further knowledge of these tumors is the aim of professionals and others interested in the subject, in the difficult course of finding better and more efficient treatment for these patients. PMID- 11205556 TI - [Epilepsy and permission to drive]. AB - INTRODUCTION: At the present time it has become a social necessity for most people to be able to drive a motor vehicle. For this reason, obtention of a driving license is continuously regulated so as to be adapted to the psychophysical aptitudes required at any given moment, since these vary with medical and social advances. DEVELOPMENT: We review the doctrine on this subject in some of the major countries, finding that far from having similar criteria, there is disparity even between different jurisdictions of the same country. In Spain epilepsy is regulated regarding the difficulty in obtaining a driving license in the General Regulation for Drivers (RD 772/1997). We consider this in detail. CONCLUSIONS: We try to unify criteria regarding the periods free of seizures, modifying the language with respect to some of these, validity of the license, analysis of the medical report and its responsibility in case of third party injury in a road accident. We propose open debate to clarify these terms. PMID- 11205557 TI - [Neuropsychological evaluation of the cognitive deficits in infection by human immunodeficiency virus type 1 (HIV-1)]. AB - INTRODUCTION: In addition to its ability to infect immune system cells, the human immunodeficiency virus type-1 (HIV-1), possesses neurotropism, that is, the virus is able to enter the central nervous system, even in patients without opportunistic brain neoplasia or infection. DEVELOPMENT: To date, two different neurologic syndrome have been recognized: one of them being mild in nature (HIV-1 associated minor cognitive/motor disorder), the other being severe (HIV-1 associated dementia complex). These syndromes are known to cause impairment in different cognitive domains, as well as psychiatric and motor complaints. Here we review the different neuropsychologic tests, experimental computerized procedures (reaction time) and examination of the different types of ocular movements, which have been used from 1981 until now, with particular emphasis on the most commonly used neuropsychologic test batteries. Our results suggest that both neuropsychologic test batteries and reaction time procedures and ocular movement examination show that, as expected, the cognitive impairment is more commonly found in HIV-1-associated dementia complex patients as compared with those with HIV-1-associted minor cognitive/motor disorder. In the latter syndrome, cognitive impairment severity correlates well to disease stage, defined according to criteria by the Centers for Disease Control. However, there continues to be an important controversy as to the occurrence of cognitive deficit in the earliest HIV-1 infection stages (medically asymptomatic stage), probably due to lack of sensibility and specificity of neuropsychologic tests and other procedures used to detect cognitive impairment in earliest stages. CONCLUSION: There is a need for improving specificity and sensibility of neuropsychologic measurements currently used to detect cognitive impairment in HIV-1 infected patients in medically asymptomatic stage. PMID- 11205558 TI - [The nervous system: important protagonist in systemic cancer]. PMID- 11205559 TI - [Special aspects of the neuro-complications of cancer]. PMID- 11205560 TI - [Notes on the history of neurological paraneoplastic syndromes]. PMID- 11205561 TI - [Paraneoplastic syndromes in otoneuro-ophthalmology]. AB - INTRODUCTION AND OBJECTIVE: The so-called neurological paraneoplastic syndromes (NPNS) are a group of diseases of the central nervous system of unknown etiology which are seen almost exclusively in patients with cancer. We review the main NPNS paying particular attention to those with ophthalmological and otological features. DEVELOPMENT: Certain neuro-ophthalmological findings may constitute, at least partly, some paraneoplastic syndromes. There are alterations of vision in paraneoplastic retinopathy and in optic neuritis of paraneoplastic origin. The latter, unlike the retinopathy, usually coexists with involvement of other structures of the nervous system. Oculomotor function is affected in the opsoclonus-myoclonus syndrome. Diplopia and/or ophthalmoplegia may be a predominant or initial symptom, in patients with paraneoplastic neurological degeneration or brainstem encephalitis. In the Lambert-Eaton syndrome and in paraneoplastic encephalomyelitis, may have blurred vision and alterations of the pupil. Cases of paraneoplastic uveitis have also been described. Paraneoplastic otological involvement is less frequent. Patients with sensorineural deafness in the context of a paraneoplastic encephalomyelitis have been reported. In the NPNS vertigo is caused by cerebellar or brainstem lesions and not by lesions of peripheral organs. When nystagmus occurs in a NPNS it may be of various types and is due to involvement of structures in the brain stem or cerebellum. CONCLUSIONS: The diagnosis of NPNS in patients with no known cancer is important because it may lead to the detection of an occult cancer which is localized or scarcely extended, and therefore is still potentially treatable. Oto-neuro ophthalmological manifestations may be the first or only symptom of presentation of a paraneoplastic neurological clinical picture. PMID- 11205562 TI - [Paraneoplastic cerebral syndromes with oto-neuro-ophthalomologic manifestations]. AB - OBJECTIVE: To review the paraneoplastic neurologic syndromes associated with otoneurophthalmologic manifestations. DEVELOPMENT: Paraneoplastic otoneurophthalmologic syndromes usually result from encephalitis of the brainstem and/or cerebellar degeneration. They can develop in association with various immunological responses against onconeuronal proteins (e.g. anti-Hu, anti-Ri, anti-Yo, anti-Ma, anti-Ta and anti-Tr) or with immunological mechanisms against unknown antigens. The eye movement abnormalities may have a supranuclear, nuclear or internuclear origin. There is no ocular movement abnormality which can be considered pathognomonic of a paraneoplastic disorder, but opsoclonus-myoclonus of infancy is often associated with neuroblastoma. The association of hearing loss and paraneoplastic sensory neuronopathy suggests that in some patients the neurosensory deafness result from involvement of the ganglia of Corti and/or the cochlear nuclei in the brain stem. The management of these syndromes depends on their rapid identification as paraneoplastic disorders and on the early diagnosis and treatment of the cancer. Patients with anti-Ta (or anti Ma-2) antibodies may improve with treatment of the cancer, usually a germ-cell tumor of the testis. Paraneoplastic opsoclonus-myoclonus of infancy usually improves with treatment that combines chemotherapy, steroids, and intravenous immunoglobulins, although neurological sequelae (psychomotor and language retardation) are frequent. CONCLUSIONS: There are several paraneoplastic neurologic syndromes that may present with otoneurophthalmologic symptoms. Detection of antineuronal antibodies facilitates the early identification of some of these syndromes and associated tumors. In general, the management of these syndromes is based on treatment of the associated cancer. PMID- 11205563 TI - [Spinal cord paraneoplastic syndromes]. AB - OBJECTIVE: We reviewed the bibliography of various paraneoplastic syndromes which may show spinal involvement. DEVELOPMENT: Paraneoplastic sensory neuropathy, myelitis and rigidity syndromes may present alone or as part of a generalized syndrome of paraneoplastic encephalomyelitis/sensory neuronopathy, usually associated with small cell cancer of the lung and anti-Hu antibodies. Amyotrophic lateral sclerosis and subacute necrotizing myelopathy of paraneoplastic origin are very rare, although casual association of these conditions with cancer cannot be ruled out. Subacute motor neuronopathy is linked to lymphoproliferative syndromes and breast cancer has been reported associated with cases of primary lateral sclerosis and the stiff man syndrome. CONCLUSIONS: Various conditions of paraneoplastic origin may affect the spinal cord. Neurological symptoms may precede the diagnosis of neoplasia, are serious and do not usually respond to either immunosuppressive treatment or treatment of the underlying neoplasm, although there are exceptions. The presence of specific antibodies in some cases facilitates early diagnosis and shows the importance of immune mechanisms in these diseases. The paraneoplastic motor neuron syndromes may present atypically: at early or late age, be of slow evolution and associated with raised protein levels of the cerebrospinal fluid or with paraproteinemia. PMID- 11205564 TI - [Paraneoplastic syndromes with peripheral nerve involvement]. AB - OBJECTIVE: To review the paraneoplastic complications described affecting the peripheral nervous system. DEVELOPMENT: Different types of tumors, especially secretory carcinomas and some lymphomas may affect the peripheral nerves, and this may often precede clinical signs of the tumor. Depending on the clinical features we may consider sensory neuropathies, motor neuropathies, senso-motor neuropathies, autonomic neuropathies, mononeuritis, and neuromyotonia. They may present in an isolated form or as part of a more generalized involvement of the nervous system. CONCLUSIONS: The presence of certain anti-Hu antibodies, which act against nerves or antibodies which attack the voltage-dependent potassium channels in a peripheral nervous system disorder make one suspect a paraneoplastic origin. PMID- 11205565 TI - [Paraneoplastic diseases of the motor end-plate and muscle]. AB - INTRODUCTION: Some forms of myasthenia gravis and many cases of Eaton-Lambert syndrome are disorders of neuromuscular transmission possibly of paraneoplastic origin. Paraneoplastic necrotizing myopathy and some cases of inflammatory myopathy (polymyositis-dermatomyositis) are paraneoplastic myopathies. DEVELOPMENT: These are all autoimmune processes. The diagnosis is clinical, based mainly on the characteristics of the muscle weakness and motor disorders, confirmed by serological methods (demonstration of antibodies) pharmacological and electromyographic tests, by imaging studies and in some cases biopsy. Treatment includes specific symptomatic measures (aimed at correcting the defect in neuromuscular transmission in the myasthenic syndromes, reducing axonal auto excitability in the neuromuscular hyperexcitability syndromes, etc.) and pathogenic treatment (basically immunosuppression). A search for the hidden tumour should also be part of the diagnostic investigation. The paraneoplastic disease may remit if the associated tumour is treated. PMID- 11205566 TI - [Meningeal carcinomatosis]. AB - INTRODUCTION: Meningeal carcinomatosis is a serious complication of solid tumors, particularly adenocarcinomas of breast, lung and melanoma. OBJECTIVE: In this paper we present a review of the bibliography on this disease, with particular emphasis on etiopathogenic, clinical--especially otoneurophthalmological- diagnostic and therapeutic aspects. DEVELOPMENT: Meningeal carcinomatosis presents in advanced stages of cancer and has an ominous prognosis with average untreated survival of from four to six weeks. Its frequency has increased in recent years since patients with systemic cancer now live longer. The characteristic of the disease is involvement of various levels of the nervous system, including encephalic, cranial or spinal nerve and spinal symptoms. Sudden loss of vision or hearing which may progress rapidly may be the initial sign of the disease. Neuroimaging studies (computerized axial tomography, magnetic resonance and isotope studies of cerebrospinal fluid flow) are necessary to evaluate associated metastases and detect obstruction of cerebrospinal fluid flow. Positive cerebrospinal fluid cytological findings confirm the diagnosis. Treatment should be tailored to the individual according to the clinical condition and nature of the tumour and should combine intrathecal chemotherapy and local radiotherapy, although recent studies have shown good results with systemic chemotherapy. CONCLUSION: A high degree of clinical suspicion is necessary for diagnosis of this uncommon disease, with neurological signs show to be present at different levels and the finding of malignant cells in the cerebrospinal fluid for confirmation of the diagnosis. PMID- 11205567 TI - [Cerebral metastasis]. AB - INTRODUCTION: Cancer and its metastatic complications are one of the most important types of disease due to their high morbidity and mortality (nearly 100%). In spite of the blood-brain barrier, the brain is one of the main targets. Paradoxically, the incidence of cerebral metastases (CM) has increased due to the progress of medical science. The clinical features of CM are particularly seen in otoneurophthalmology (ONO). OBJECTIVE: To review the pathophysiology, etiology, prognosis, complementary tests and clinical features of the CM, particularly the findings of most importance in ONO. MATERIAL AND METHODS: Data on MC was obtained from MEDLINE and Cancerlit for the period 1991 to 2000. The cases of CM seen in three hospitals of different communities and levels of healthcare are also reviewed. RESULTS: The CM are mainly situated in the cortical and juxtacortical zones, causing seizures which together with headache and mental and focal motor syndromes, make up the main clinical findings. Cancer of the lung and breast are the main causes of CM, whilst cancer of the prostate metastasizes more to the base of the skull and spinal coverings. Melanoma has the greatest tendency to metastasize. In spite of surgery, radiotherapy and chemotherapy the average survival with CM is three months. CONCLUSIONS: CM is a diagnosis which should be considered in patients of middle age or older. The lung is the most usual site of origin. In spite of the dreadful prognosis, the doctor plays a decisive part in both aggressive and palliative measures. PMID- 11205568 TI - [Surgical treatment of brain metastases]. AB - INTRODUCTION: Up to 40% of the patients with cancer have cerebral metastases, so that their incidence in the general population reaches 0.15%. Different treatments for metastases have been described. Most aim to eradicate one or several metastases so as to improve the quality of life and life expectancy of the patients. DEVELOPMENT: The main factors determining the prognosis and indication for surgery are age, functional state and extent of the neoplastic disease. The presence of more than one metastasis does not contraindicate surgery. CONCLUSIONS: The development of new surgical techniques over the past twenty years has led to a reduction in operative morbidity and mortality. Surgery followed by holocranial radiotherapy is still the method of choice for the treatment of metastases. In cases in which surgical treatment is not indicated, radiosurgery may be done. PMID- 11205569 TI - [Cerebrovascular disease in the cancer patient]. AB - OBJECTIVE: To make an up-to-date review of the literature on cerebrovascular disease of the patient with cancer. DEVELOPMENT: Approximately 15% of the patients with cancer have cerebrovascular disease. The frequency of cerebral infarcts is similar to that of cerebral hemorrhage. The commonest mechanisms of cerebral ischemia are atherosclerosis, non-bacterial thrombotic endocarditis, disseminated intravascular coagulation, infection, tumour embolism and thrombosis of the longitudinal venous sinuses. The most usual mechanisms of cerebral hemorrhage are intratumoural hemorrhage, hypertensive hemorrhage and the coagulopathies. In the Stroke Register of the Hospital del Sagrat Cor in Barcelona, of a total of 1,099 patients with their first cerebrovascular episode, in 14 patients the stroke (12 infarcts and two intracerebral hemorrhages) were the form of onset of a previously unrecognised hematological disorder. The hematological neoplasias were the commonest form of hematological disorders, mainly essential thrombocythemia, which was diagnosed in six patients. CONCLUSIONS: The clinical management and care of patients with stroke and cancer differ from that of patients with stroke alone, since the cause is different from that of non-neoplastic patients. PMID- 11205571 TI - [Metastatic and paraneoplastic lesions of the optic nerve]. AB - We review the involvement of the optic nerve in distinct neoplastic disorders and differentiate the metastases from the paraneoplastic disorders. We also review and discuss the role of malignant lymphoreticular disorders, solid tumors and meningeal carcinomatosis in relation to the changes in the optic nerve caused by these conditions. PMID- 11205570 TI - [Infectious and metabolic nervous system complications of systemic cancer]. AB - OBJECTIVE: To review the incidence and causes of the infections and metabolic diseases of the nervous system in patients with systemic neoplasias. DEVELOPMENT: Patients with immunodeficiency, particularly those with hematological neoplasias and persons treated with immunosuppressive drugs have a considerable tendency to infection due to opportunist germs. Infections of the nervous system are relatively rare (0.02%-1%) and the commonest neoplasms are lymphomas, especially those of Hodgkin type and lymphosarcomas. The most frequent infections are caused by the herpes virus, meningitis due to Listeria monocytogenes and the meningitis due to fungi (Aspergillus, Candida and Cryptococcus). Cerebral abscesses, although rarer, are relatively common and are caused by gram negative bacteria, fungi and toxoplasmosis. In recent years there has been a notable increase in the number of patients diagnosed as having progressive multifocal leukoencephalopathy due to the possibility of carrying out studies to detect the DNA of the JC virus by polymerase chain reaction techniques. Empirical treatment of patients with neurological infections and systemic cancer should be started following the guidelines for immunodepressed patients. The metabolic complications of these patients are mainly due to hormone overproduction, hydroelectrolytic changes and vitamin deficits, which in general cause alterations of mental function of the confusion state type. CONCLUSION: In all patients with an infection or metabolic complication involving the nervous system, the presence of a systemic neoplasm makes it necessary to vary both the diagnostic approach and the empirical therapeutic measures taken. PMID- 11205572 TI - [Intraocular manifestations of systemic cancer]. AB - Systemic cancer may present intraocular features in three forms: as a sign of the presence of lymphoreticular tumors, of solid tumors or as a paraneoplastic syndrome. PMID- 11205573 TI - [Orbital metastasis in the adult]. AB - Metastases to the orbit are uncommon in adults and form a small proportion of the diseases of the orbit. In the orbit, metastases cause symptoms due to the space occupying effect or to infiltration of the structures within the orbit. PMID- 11205574 TI - [Ophthalmological manifestations of systemic cancer in childhood]. AB - Metastases to the orbit in childhood may be due to solid tumors such as a neuroblastoma or Ewing's tumor. The lymphoreticular diseases are also a major cause of metastases to the eye in children. PMID- 11205575 TI - [Metastasis of systemic origin in otorhinolaryngology]. AB - INTRODUCTION: In the upper respiratory-digestive tract cancer is always primary. Such cancer is very common, but other extremely rare secondary cancers may be found. DEVELOPMENT: We studied our own patients and some published in the literature: cancer of the kidney with metastases in the paranasal sinuses and cancer of the breast metastasizing to the temporal bone. We review the bibliography on these rare metastases. CONCLUSIONS: In all cases of otorhinolaryngological cancer a detailed history should be taken, with special reference to previous neoplasms. It is particularly important to study and review any history of renal, breast or prostate tumors with regard to the primary tumor and the receptor organs of metastases, the paranasal sinuses and temporal bones. The most difficult problem occurs when the primary tumor is present but undiagnosed. Therefore, in all cases of cancer of the paranasal sinuses and temporal bones, before treatment is started the kidney, prostate, breast and other organs above and below the diaphragm where tumor may be present should be examined. The prognosis of these metastases, which are almost always fatal, is very poor so that often treatment is only palliative rather than aggressive. PMID- 11205577 TI - [Non-Hodgkin's lymphomas: current aspects]. AB - OBJECTIVE: We wish to briefly review current knowledge of non-Hodgkin lymphomas (NHL) with special emphasis on aspects of interest in ophthalmology, otorhinolaryngology and neurology. DEVELOPMENT: We analyze the historical evolution of the classification of the NHL and refer to that recently devised by the World Health Organization. Amongst the numerous conditions forming part of this group of disorders we refer to the main data (clinical, immunophenotype, cytogenetics and of molecular biology) relative to the five most important types: 1. Follicular lymphoma; 2. Diffuse large cell lymphoma; 3. 'Mantle' cell lymphoma; 4. MALT lymphoma (mucosa associated lymphoid tissue), and 5. Peripheral T lymphoma. Then we describe the types and clinical forms of NHL in ophthalmology, otorhinolaryngology and neurology. Finally we consider the recent advances in prognosis (international index, biological markers) and treatment (new types of polychemotherapy, eradication of Helicobacter pylori, transplant of hemopoietic progenitors, monoclonal antibodies and anti-sense treatment of these conditions. CONCLUSIONS: The NHL form a group of conditions in which the annual increase in recent years has been over 4%. With considerable frequency these tumors are found from the beginning or during their course in otorhinological and ophthalmic tissues, or in the nervous system; in the latter case, apart from direct tumour expression they may also cause paraneoplastic manifestations. PMID- 11205576 TI - [Oncologic treatment of oto-neuro-ophthalmological metastases and their complications]. AB - INTRODUCTION: Cerebral metastases and the sequelae of their treatment are the major cause of neurological symptoms in patients with cancer. OBJECTIVE: In this article we review the oto-neuro-ophthalmological complications of the treatment of metastases with radiotherapy and/or chemotherapy. DEVELOPMENT: When speaking of the iatrogenic diseases caused by radiotherapy treatment of metastases, it is important to emphasize that the major complications of this form of treatment are seen in the long term, in general, months or years later. When dealing with incurable diseases, such as most metastatic cancers, the benefit/risk balance of each therapeutic option has to be taken into account. Thus we have a population of patients with symptoms secondary to metastatic involvement, and with an overall life expectancy which may be measured in months. The oto-neuro ophthalmological toxicity of the chemotherapy may present as an infrequent and unexpected complication or as a usual, expected secondary effect of the drug used. A large variety of drugs are used for the systemic control of cancer (cystostatic drugs, hormones and modifiers of the biological response) which, in one way or another, may cause neurological signs. CONCLUSION: The increasingly frequent use of high dose chemotherapy and of the combined use of chemotherapy and radiotherapy mean that these types of toxicity have become common clinical syndromes in current oncological practices. PMID- 11205578 TI - [Spontaneous cervical epidural hematoma]. PMID- 11205579 TI - The resonance frequencies on mechanically pre-stressed ultrasonic piezotransducers. AB - The piezotransducers employed in high power ultrasound are composed of piezoelectric ceramics and metallic pieces. These transducers are mechanically pre-stressed in order to avoid the ceramic fractures when high voltage is applied under resonance. The resonance and anti-resonance frequencies are shifted depending on the level of applied mechanical pre-stressing. This paper discusses some causes of this shifting on a experimental study. The discussion takes into account the variations on characteristic parameters of the ceramics and the acoustic coupling between parts of the transducer. PMID- 11205583 TI - A multiple focused probe approach for high intensity focused ultrasound based surgery. AB - To produce deep-seated surgical lesions using ultrasound requires high power and intensity levels at the target sites. Conventionally, large transducers are used which require big apertures and so are generally suitable only for extra corporeal access. Such transducers also result in strong off-focus maxima, where the resulting hot spots can destroy normal tissue whilst deep-seated large tissue volumes are being ablated. This paper describes a new approach in which it is proposed that multiple probes are used simultaneously, each at a relatively low power, to result in an overlapping focused region of high temperature without strong off-focus hot spots. Robotic techniques could be used to move the individual probes in coordination to sweep out the desired region of tissue ablation. Simulation and planning are the key to quality prediction for high intensity focused ultrasound (HIFU). Simplified two-dimensional and three dimensional models of HIFU probes have been developed to study the characteristics of various multi-probe configurations. Preliminary simulation results show that the multi-probe system can be arranged successfully to minimise off-focus hot spots. Experimental results are presented which validate the modality and confirm this positive finding. Further prediction studies and planning will be necessary to achieve the most appropriate desired treatment, by varying the pulse duration and spacing. PMID- 11205588 TI - The mechanical pre-stressing in ultrasonic piezotransducers. AB - Composed piezotransducers submitted to mechanical pre-stressing present shifts on resonance and anti-resonance frequencies. Changes on characteristic parameters of the ceramic and in the coupling between the parts of the transducer can be the causes for this behavior. In applications where the level of pre-stressing is low (up to 50 MPa) the parameters of the ceramic are not altered, therefore, the shifting on frequencies are attributed to coupling between parts. This paper describes a mathematical model to explain this effect based on difference of effective cross-section between transducers parts under pre-stressing. The results show a proportional relation between pre-stressing and effective coupling of the parts. PMID- 11205589 TI - Push, pull, divide or destroy. PMID- 11205590 TI - Health sector decentralization and management: developing a district general policy on management. PMID- 11205591 TI - Successful treatment of scabies with oral ivermectin in Nigeria. AB - Currently, several topical scabicides are available but there is yet no oral or parenteral drug which has been established for the treatment of scabies in Nigeria. Ivermectin which is a modified avermectin, known to be an ectoparasiticidal agent in animals, has been used in adults for systemic parasitosis. In Nigeria, 25% benzyl benzoate is being extensively used for the treatment of scabies in adults. It is effective and readily available. The present study was carried out to evaluate the efficacy and safety of ivermectin in the treatment of patients with scabies at the skin clinic of the University of Nigeria Teaching Hospital, Enugu. Fifty-eight patients with scabies were recruited for the study; 13 (22.4%) were children aged between 5-14 years. Oral ivermectin was given in a single dose of 200 [microg/kg body weight to 29 patients. The remaining 29 patients had to apply 25% benzyl benzoate emulsion. All patients received a full physical and dermatological examination prior to onset of treatment and weekly for 4 weeks. Skin scrapings were taken to confirm the diagnosis of scabies. There was a 93% resolution of pruritus with ivermectin and 48% with benzyl benzoate. No side effects were observed with ivermectin. Our results show that oral ivermectin is a promising, effective and safe alternative in both children and adults of Nigeria when compared to 25% benzyl benzoate topical application. PMID- 11205593 TI - Lymphoedema. PMID- 11205592 TI - Field trial of the RTM dipstick method for the rapid diagnosis of malaria based on the detection of Plasmodium falciparum HRP-2 antigen in whole blood. AB - The performance of the Quorum RapidTest Malaria (RTM) dipstick method that detects Plasmodium falciparum histidine-rich protein-2 (PfHRP-2) antigen in whole blood was evaluated in a malaria endemic area. Results were compared with conventional Giemsa-stained blood films. Of 306 people tested 37.9% (116/306) were found to be parasitaemic; of these 66.4% (77/116) were P. vivax and 32.8% (38/116) were P. falciparum infections. There was only one (0.9%) mixed P. falciparum plus P. vivax infection. The RTM test was positive in 35/36 patients with P. falciparum identified on blood smear examination, resulting in a sensitivity of 97.2% [95% confidence interval (CI): 91.6-102.8%]. Specificity was 96.3% (95% CI: 93.9-98.6%). The RTM test had a positive predictive value of 77.8% (95% CI: 65.7-89.9%) and a negative predictive value of 99.6% (95% CI: 98.4 100.8%). Of the 10 false positives, seven reported recent malaria episode and treatment, indicating persistence of antigenaemia. If these were assumed truly infected, the positive predictive value is increased to 93.3% (95% CI: 85.8 100.8%). The RTM test was positive in all seven P. falciparum infections with gametocytes and one mixed infection, but was negative in all falciparum gametocytes and relapsing fever cases. All but one P. vivax infection gave negative result on the RTM test. The RTM test missed one patient with parasitaemia. The test is highly sensitive and specific requiring no instrument or trained personnel. It appears to be a very useful tool for rapid diagnosis of malaria, especially in the rural health institutions with limited diagnostic facilities. PMID- 11205594 TI - Improving immunization coverage in rural areas of Ecuador: a cost-effectiveness analysis. AB - This study describes the costs and outcomes of two different immunization strategies used by the district level of the Ministry of Health carried out between 1993 and 1995 in Low-Napo area, Napo, Ecuador. One was centrally planned and managed by the District Hospital (DH) and the other planned and implemented together with community health workers (CHW). Immunization costs were estimated directly from survey records and communication of the Ministry of Health. Outcomes information was abstracted from the vaccination statistics of the Napo Province Health Department for 1993/1995. Community health workers strategy immunized 113 children with an average cost of US $32 per child. District Hospital strategy had an average cost of US $777.6 per immunized child.Thus, CHWs strategy is more effective and less costly than the DH strategy. This study shows that in order to maximize the cost-effectiveness of immunization, it is important to involve community participation in both planning and implementation. Continuous follow-up and evaluation of the immunization programme and further research on vaccine efficacy are necessary in order to maintain these results. PMID- 11205595 TI - Colostomy in neonates with a massively distended abdomen due to an imperforate anus. AB - A simple technique of intraoperative decompression and colostomy in neonates with a massively distended abdomen is described. With this technique, the handling of distended bowel becomes easier and peritoneal contamination by meconeum is also prevented. PMID- 11205596 TI - Associated morbidities in children with sickle-cell anaemia presenting with severe anaemia in a malarious area. AB - A prospective study of 104 consecutive cases of patients with sickle-cell anaemia (SCA) presenting with severe anaemia (packed cell volume < or = 15%) was carried out in the Children's Emergency Ward of the University College Hospital, Ibadan, in 1991. The patients were classified according to the type of anaemic crisis, by physical findings, serum bilirubin and reticulocyte counts. Other investigations included a blood film for malaria parasites, blood culture, radiological investigation and lumbar puncture when necessary. The most common problems associated with SCA patients in anaemic crisis were malaria and bacterial infections--68 (66%) and 18 (17.3%) of cases, respectively. Acute chest syndrome was significantly more frequent in patients with hyperhaemolytic and acute splenic sequestration crisis compared with aplastic crisis (P < 0.05). Conjugated hyperbilirubinaemia was also significantly more frequent among patients with hyperhaemolytic crisis compared with all other anaemic crises (chi2 = 13.18, P = 0.001). The overall case fatality was 86.5/1,000 SCAs, with no fatalities in those with aplastic crisis. There were complications in six of the nine mortalities. Co-existing bacterial infections and conjugated hyperbilirubinaemia were associated with increased morbidity and mortality in patients with anaemic crisis. Patients with SCA crisis should have early evaluation and prompt treatment for associated infections. PMID- 11205597 TI - Complications of chronic arsenic poisoning. PMID- 11205598 TI - Service improves performance of unattended draw-over halothane vaporizers. AB - The accuracy of the output halothane concentration of seven draw-over halothane vaporizers (TEC, Ohmeda) which were delivered in 1986 to Malawi was investigated. They had not been serviced for the past 8 years. The output was studied at dial settings of 0.5%, 1%, 2%, 3%, 4%, and 5% at minute volumes of 2 to 8 litres before and after thorough cleaning of the vaporizers. The measured halothane concentration was corrected to sea level. Of seven vaporizers one was delivering concentrations up to 240% higher than the setting. A second vaporizer delivered concentrations much lower than the setting; the maximum output was 1.5% at the 5% setting. After cleaning, all vaporizers delivered concentrations close to the dial setting. The maximum deviation from the setting was 0.5% at the 0.5%, 1% and 2% setting and 0.9% at higher settings. Whether the replacement of damaged wicks and seals would improve the accuracy further could not be investigated because these spare parts were not available. It is concluded from this study that regular servicing of draw-over vaporizers is essential. Support for the training of technicians in developing countries and also support for the funding of spare parts and measuring instruments in these countries should be considered by donors. PMID- 11205599 TI - A clinico-epidemiological study of organophosphorus poisoning at a rural-based teaching hospital in eastern Nepal. AB - Thirty-seven patients with severe organophosphorus poisoning (OPP) presented to the emergency ward of BP Koirala Institute of Health Sciences between January 1995 and December 1996. The mean age of patients was 26.9 years. There were 17 (46%) males and 20 (54%) females, with male:female ratio being 1:1.2.Twenty-three (62%) patients were unmarried with 16 (46%) of them students. The most common reason for poisoning was suicide--32 patients (86.5%). The most commonly involved compound was Metacid (methyl-parathion)--23 (62%) patients. Ninety per cent of the patients presented within 2 h of ingestion. All patients were managed with intravenous atropine. Pralidoxime was given to patients with nicotinic symptoms and mechanical ventilation initiated in patients with respiratory distress. The mean dose of atropine used in the first 24 h and during the hospital stay was 30.6 mg and 136.7 mg, respectively. The mean duration of treatment was 5.5 days (range 2-20 days). Two patients developed intermediate syndrome and the overall mortality among hospitalized patients was 8%. PMID- 11205600 TI - Drug Revolving Funds: a low-cost sustainable intervention? PMID- 11205601 TI - Train the trainers course on infection control and hospital hygiene in Bangladesh. PMID- 11205602 TI - Outcome of extracapsular cataract surgery plus posterior chamber intraocular lens insertion for age-related cataract in eastern Nepal. AB - As age-related cataract is the leading cause of blindness in Nepal, much more attention should be given to improving surgical outcomes. The aim of our study was to determine the effectiveness and risks of extracapsular cataract surgery (ECCE) for age-related cataract in a tertiary hospital of eastern Nepal. ECCE with posterior chamber intraocular lens (PC IOL) insertion on 797 eyes (754 patients) revealed improved visual acuity in 97.9%. In 595 (74.6%) the best corrected visual acuity was 6/18 or better, and 167 (20.9%) had 6/24 to 6/60 with negligible operative/postoperative complications. Thus it is concluded that ECCE with PC IOL could be performed safely and effectively even in developing countries where people are unaware that surgery is available and of the good surgical outcome. PMID- 11205603 TI - Disengaging impacted head at caesarean section for obstructed labour--push or pull? PMID- 11205605 TI - Assessment of ability of Nigerian mothers to recognize anaemia in children with malaria. PMID- 11205604 TI - The management of nephroblastoma in a rural hospital. PMID- 11205606 TI - Influence of HIV infection on presentation of Kaposi's sarcoma. AB - We report a retrospective review of 57 patients with endemic Kaposi's sarcoma (EKS) seen between 1981 and 1990 and 40 prospectively diagnosed patients with and without human immunodeficiency virus (HIV) infection seen between 1991 and 1995. In the retrospective study 52 patients were males and five were females. Their ages ranged between 15 and 62 years with a mean of 39 years.Thirty-five (61%) patients had symptoms for more than 1 year. Nodular KS was seen in 75% of the patients. In the prospective study 26 patients had EKS while 14 had AIDS associated KS (AAKS). Among the patients with EKS 24 were males and two were females. The mean duration of symptoms was 20 months. The CD4 count done on nine patients ranged between 900 and 1300 cells/mm3 and there was no mortality within 1 year of presentation. Eleven of the patients with AAKS were males and three were females. Their ages ranged between 22 months and 41 years with a mean of 26. Nine patients had symptoms for less than 6 months. Ten patients had peripheral lymphadenopathy. CD4 counts done on 11 patients ranged between 200 and 800 cells/mm3. Five patients (35%) died within 6 months of presentation. Between 1991 and 1995, 486 patients were seen with HIV infection. Patients with AAKS present with fulminant disease which seemed quickly fatal. PMID- 11205607 TI - Abdominal fasciocutaneous flap for upper extremity wound coverage in the developing world: indications and complications. PMID- 11205608 TI - Distribution of ABO and Rh-D blood groups among blood donors in a tertiary care centre in South India. AB - The distribution of ABO and Rh-D blood groups was studied among 150,536 blood donors screened at the Dr John Scudder Memorial Blood Bank, Christian Medical College Hospital, Vellore, over a period of 11 years (April 1988 to March 1999). The most common blood group was found to be group O [58,330 (38.75%)], followed by group B [49,202 (32.69%)], and group A [28,372 (18.85%)]. The least common blood group was AB group [7,930 (5.27%)]. A2 or A2B groups were found in 3.01% and 1.43% of donors, respectively. The prevalence of Rh-D negative group was found in 8,225 (5.47%) donors. Bombay group (H negative non-secretor, genotype hh phenotype Oh) was found in six donors (0.004%). Although the incidence of Rh-D negative group was identical to previously published data from North India, the most common blood group was O group in our study as opposed to B group. PMID- 11205609 TI - B-ultrasound and computed tomography scan diagnosis of 32 cases of intraorbital dermoid cysts. PMID- 11205610 TI - The management of club foot. PMID- 11205611 TI - Female genital mutilation and reproductive health: does publicity help to improve women's health? PMID- 11205612 TI - HIV and syphilis in pregnant women at a tertiary care hospital. PMID- 11205613 TI - Hypoglycaemia in Salmonella typhi. PMID- 11205614 TI - Factors militating against the effective implementation of the essential drug list. PMID- 11205615 TI - Palliative total gastrectomy in advanced gastric cancer. PMID- 11205616 TI - Indications and results of right hemicolectomy in Ilorin, Nigeria. PMID- 11205617 TI - Better oxygenation in newborns without extra oxygen. PMID- 11205618 TI - HIV/AIDS in Pakistan. PMID- 11205619 TI - Prisoners with HIV/AIDS: a participatory learning and action initiative in Malaysia. AB - Rapid participatory research and project development is possible within a tightly controlled social context such as a prison. Having gained access, based on trust and mutual respect, external agents may then facilitate significant change. Given adequate support, incarcerated people with HIV/AIDS and limited medical access may be able to develop mutual care, social support and income-generating activities. In the Malaysian context, we estimated in 1998 that up to one-quarter of prisoners with HIV had indicators of significant disease. We estimated that significant indicators remained unrevealed among between one-half and two-thirds of these. Given prevailing conditions, these would probably only be amenable to peer-based care. PMID- 11205620 TI - Post-stroke depression or fatigue. PMID- 11205621 TI - Current trends in the understanding and treatment of social phobia in youth. AB - Social phobia is a common psychiatric problem in children and adolescents that has recently gained serious attention in clinical practice and research. This article describes the clinical presentation of social phobia and reviews several emergent areas of related research to social phobia in children and adolescents. We begin with a summary of research regarding the developmental pathways of childhood social anxiety into social phobia, highlighting normative developmental factors, behavioral inhibition, pathophysiology, genetics, and parenting/environmental factors. This is followed by a critical review of findings from studies providing evidence for and against the existence of subtypes of social phobia. Common comorbid disorders and sequelae of social phobia in children and adolescents are discussed, bringing to attention the critical need for effective treatments, the current status of which is reviewed in the final section. In sum, this review demonstrates that through research in multiple disciplines, scientists are now developing a better understanding of the risk and protective factors of social phobia in children and adolescents, ultimately leading to improvements in primary prevention and intervention efforts for children at serious risk for long-term problems with education, employment, social relationships, and independent adult functioning. PMID- 11205622 TI - Multilevel modelling of hierarchical data in developmental studies. AB - This report attempts to give nontechnical readers some insight into how a multilevel modelling framework can be used in longitudinal studies to assess contextual influences on child development when study samples arise from naturally formed groupings. We hope to achieve this objective by: (1) discussing the types of variables and research designs used for collecting developmental data; (2) presenting the methods and data requirements associated with two statistical approaches to developmental data--growth curve modelling and discrete time survival analysis; (3) describing the multilevel extensions of these approaches, which can be used when the study of development includes intact clusters or naturally formed groupings; (4) demonstrating the flexibility of these two approaches for addressing a variety of research questions; and (5) placing the multilevel framework developed in this report in the context of some important issues, alternative approaches, and recent developments. We hope that readers new to these methods are able to visualize the possibility of using them to advance their work. PMID- 11205623 TI - Infant intersubjectivity: research, theory, and clinical applications. AB - We review research evidence on the emergence and development of active "self-and other" awareness in infancy, and examine the importance of its motives and emotions to mental health practice with children. This relates to how communication begins and develops in infancy, how it influences the individual subject's movement, perception, and learning, and how the infant's biologically grounded self-regulation of internal state and self-conscious purposefulness is sustained through active engagement with sympathetic others. Mutual self-other consciousness is found to play the lead role in developing a child's cooperative intelligence for cultural learning and language. A variety of preconceptions have animated rival research traditions investigating infant communication and cognition. We distinguish the concept of "intersubjectivity", and outline the history of its use in developmental research. The transforming body and brain of a human individual grows in active engagement with an environment of human factors--organic at first, then psychological or inter-mental. Adaptive, human responsive processes are generated first by interneuronal activity within the developing brain as formation of the human embryo is regulated in a support system of maternal tissues. Neural structures are further elaborated with the benefit of intra-uterine stimuli in the foetus, then supported in the rapidly growing forebrain and cerebellum of the young child by experience of the intuitive responses of parents and other human companions. We focus particularly on intrinsic patterns and processes in pre-natal and post-natal brain maturation that anticipate psychosocial support in infancy. The operation of an intrinsic motive formation (IMF) that developed in the core of the brain before birth is evident in the tightly integrated intermodal sensory-motor coordination of a newborn infant's orienting to stimuli and preferential learning of human signals, by the temporal coherence and intrinsic rhythms of infant behaviour, especially in communication, and neonates' extraordinary capacities for reactive and evocative imitation. The correct functioning of this integrated neural motivating system is found to be essential to the development of both the infant's purposeful consciousness and his or her ability to cooperate with other persons' actions and interests, and to learn from them. The relevance of infants' inherent intersubjectivity to major child mental health issues is highlighted by examining selected areas of clinical concern. We review recent findings on postnatal depression, prematurity, autism, ADHD, specific language impairments, and central auditory processing deficits, and comment on the efficacy of interventions that aim to support intrinsic motives for intersubjective communication when these are not developing normally. PMID- 11205624 TI - Research in mental retardation: toward an etiologic approach. AB - Over the past two decades, mental retardation research converges on three general themes: co-occurring mental retardation and psychopathology; families of offspring with mental retardation; and the developmental approach regarding behavioral sequences and profiles. Intertwined with each theme is a mounting body of research on genetic mental retardation syndromes. We first review recent progress in each of the three domains--psychopathology, families, and development -based on studies of groups with heterogenous or nonspecific mental retardation. We then show how new findings from specific genetic syndromes take this knowledge even further, as well as aid in the search for genetic, physiological, and environmental mechanisms associated with certain behaviors. We end the review by briefly summarizing our reasons for promoting an etiological approach to future mental retardation research, as well as by discussing methodological and other challenges. PMID- 11205625 TI - Pediatric psychopharmacology. AB - This paper reviews research in pediatric psychopharmacology over the past decade. The authors first discuss social, economic, and other influences on pediatric psychopharmacology research and prescribing patterns including changing models of childhood psychopathology, increased government funding, and changes in industry regulations. Definitions are offered for current research terminology including efficacy, effectiveness, and adverse events. Design trends and new approaches to outcome measurement are also presented. New data from the last 10 years of research is reviewed for each major class of psychotropic agents. Criteria for inclusion in the review are presented and include aspects of study design (placebo-controlled, large sample size), source of funding (government funded vs. industry), and vision (creative applications). Data for short-term efficacy, long term efficacy, effectiveness, and safety and adverse events are discussed for each class of medication, although for many, there remains little empirical data. Findings for stimulants, selective serotonin reuptake inhibitors, neuroleptics, alpha-adrenergic agonists, mood stabilizers, buproprion, secretin, naltrexone, immune therapies, and natural supplements are all presented. Finally, the authors offer some speculations regarding the future of pediatric psychopharmacology research. PMID- 11205627 TI - The exciting future of antifungal therapy. AB - Invasive fungal infections are becoming more common. Current therapy is generally limited to amphotericin B in its parent and lipid formulations, 5-fluctyosine, fluconazole, and itraconazole. Toxicity, drug-drug interactions, and increasing fungal resistance reduce the usefulness of these drugs, and the need for new therapies is pressing. This article briefly discusses the limitations of antifungal minimum inhibitory testing, and then summarizes new antifungal drugs in development that have been tested in humans. It also addresses novel treatment strategies such as drug combination therapy, pharmacological reformulations to improve the efficacy or reduce the toxicity of current antifungal drugs, immune function augmentation, and vaccine development. All of these strategies, although in their infancy, will enhance the clinician's ability to care for patients with invasive fungal infections. PMID- 11205626 TI - Developmental dyslexia: an update on genes, brains, and environments. AB - The science of reading and developmental dyslexia has experienced spectacular advances during the last few years. Five aspects of this research are discussed in the article. (1) The holistic phenomenon of reading is complex. Many lower level psychological processes (e.g., phonemic awareness, phonological decoding, ability to process stimuli rapidly and automatize this process, memory, ability to recognize words) contribute to a single act of reading. Conceptualizing the complex process of reading through its partly overlapping but partly independent components--which contribute to, but do not fully explain, the holistic process of reading--provides an excellent model for understanding complex hierarchies of higher mental functions. Those who master reading skills successfully and those who have difficulties doing so differ in a wide range of reading-related processes. The central deficit experienced by poor readers appears to be related to phonological processing (a complex hierarchy of functions related to processing phonemes), whereas characteristics of automatization processes seem to moderate the reading outcome for people whose phonological skills are weak. (2) There are new data addressing models of dyslexia in languages other than English. The most fascinating finding is that the model implicating phonological deficit as central to dyslexia, and the lack of ability to automatize as leading to troubled reading, appears to be universal, regardless of the specific language. However, there is an interaction effect between the characteristics of a particular language and the developmental model of dyslexia. In phonologically more difficult languages (e.g., English), the most pronounced weakness appears to occur in phonological processing, whereas in phonologically easier languages (e.g., German), the crucial role in the manifestation of dyslexia is played by the lack of the skills needed to achieve automatization. (3) There is abundant evidence that reading (i.e., any single act of reading as well as reading as a holistic process) is "cooked" by the brain. Although no unified brain map of reading has been developed, some specific areas of the brain have been implicated in different reading-related cognitive processes by different laboratories and on different samples. (4) Indisputable evidence has been accumulated suggesting the involvement of the genome in developmental dyslexia. As of now, specific regions of the genome have been identified as being intimately involved with a number of different reading-related processes. Today the field of developmental dyslexia is the only area of genetic studies of human abilities and disabilities in which linkages to the genome have been robustly replicated in independent laboratories. (5) Finally, evidence suggests that developmental dyslexia might be only one of the manifestations of a deep, underlying, anatomical syndrome. The comorbidity of developmental dyslexia with both internalizing and externalizing behavioral disturbances, as well as with other learning disabilities, underscores the need for wide-ranging cognitive and behavioral approaches in the remediation programs offered to dyslexic children. PMID- 11205628 TI - Review of the incidence and prognosis of Pseudomonas aeruginosa infections in cancer patients in the 1990s. AB - In an attempt to determine the actual relevance of Pseudomonas aeruginosa as a target of empiric antimicrobial first-line therapy in febrile cancer patients, 44 reports of clinical trials on antimicrobial treatment regimens and 53 reports on the epidemiology of microbiologically documented infections in cancer patients were reviewed. The incidence of infections due to Pseudomonas aeruginosa was 1 2.5% among all patients presenting with first fever during neutropenia, and 5-12% among patients with microbiologically documented infections. The proportion of Pseudomonas aeruginosa infections among cases of gram-negative bacteremia has not generally declined during the past 2 decades. There were marked local and regional differences regarding the incidence of documented Pseudomonas aeruginosa infections. No clear differences between neutropenic and non-neutropenic cancer patients, between patients with solid tumors and those with hematologic malignancies, or between inpatients and outpatients presenting with fever and neutropenia were detected with respect to the likelihood of Pseudomonas aeruginosa involvement. The mortality rate in patients with Pseudomonas aeruginosa bacteremia, particularly with polymicrobial bacteremia or bacteremic pneumonia with Pseudomonas aeruginosa involvement, is considerably high. The beneficial impact on mortality of an empiric antimicrobial treatment regimen with high antipseudomonal activity has not yet been demonstrated unequivocally. Additional factors such as the quality of intensive care management, effective second-line antimicrobial regimens, local resistance patterns, and patient related cofactors are very likely to influence the outcome of Pseudomonas aeruginosa infections in cancer patients. PMID- 11205629 TI - Seven-year study of bacteraemic pneumonia in a single institution. AB - In order to enhance current knowledge of nosocomial and community-acquired bacteraemic pneumonia in a single tertiary hospital in Israel, a 7-year study was conducted. Using a computerised database, all patients who had bacteraemic pneumonia from March 1988 to August 1995 were studied. During the study period, pneumonia was the source of bacteraemia in 319 of 4,548 (7%) episodes, occurring in 295 patients; 211 (66%) episodes were community-acquired and 108 (34%) were nosocomial. The microoroganisms isolated most frequently from patients with community-acquired bacteraemic pneumonia were Streptococcus pneumoniae (46%), Staphylococcus aureus (10%) and Haemophilus influenzae (8%); while Pseudomonas spp. (17%), Klebsiella spp. (11%) and Staphylococcus aureus (10%) were isolated most often from the patients with nosocomial bacteraemic pneumonia. The median age of patients was 68 years (range, 0.003-100). The overall mortality was 34%. No significant difference was found between the mortality rates of patients with community-acquired (31%) and nosocomial (40%) bacteraemic pneumonia (P=0.1). Multivariate analysis showed that hypothermia, respiratory failure, impaired consciousness, tracheal intubation, Staphylococcus aureus aetiology, septic shock, inappropriate empiric antibiotic treatment and age significantly increased mortality. PMID- 11205630 TI - Detection of seroconversion and persistence of Chlamydia trachomatis antibodies in five different serological tests. AB - Microimmunofluorescence (MIF), a Chlamydia trachomatis species-specific enzyme immunoassay incorporating lipopolysaccharide-extracted Chlamydia trachomatis L2 elementary bodies, two different synthetic peptide-based species-specific tests, and a recombinant lipopolysaccharide genus-specific test were performed on multiple follow-up sera (n = 104 total) from 16 women with Chlamydia trachomatis positive cervical swabs. These women included five with IgG seroconversions, five with Chlamydia trachomatis reinfections after initial therapy, and six with serologic follow-up of more than 6 years after antibiotic therapy. Of all the tests employed in this study, MIF IgG reverted earliest to negative titers, while MIF IgA was the least sensitive. The lipopolysaccharide-extracted elementary body enzyme immunoassay exhibited the closest correlation with the MIF test. The highest test sensitivity was observed in one of the synthetic peptide-based tests, which detected earliest seroconversions and longest IgG persistence. The other synthetic peptide-based test gave false-negative results in 2 of 16 women and did not detect seroconversion earlier than the MIF test. Seroconversion and persistence of genus-specific IgG--cross-reactivity with Chlamydia pneumoniae- against lipopolysaccharide were similar to species-specific IgG. A significant serologic response to reinfection was observed only in women with signs of pelvic inflammatory disease. Species-specific tests of high sensitivity and reproducibility are best suited for gynecological diagnostic purposes. PMID- 11205631 TI - Mycobacterial growth indicator tube versus the proportion method on Lowenstein Jensen medium for antibiotic susceptibility testing of Mycobacterium tuberculosis. AB - The Mycobacterial Growth Indicator Tube, a reliable system for detection of mycobacterial growth, was compared with the reference proportion method on Lowenstein-Jensen medium for antibiotic susceptibility testing of Mycobacterium tuberculosis. A total of 62 clinical strains and four reference strains of Mycobacterium tuberculosis were tested for susceptibility to streptomycin, isoniazid, rifampicin and ethambutol. Of these, 36 were susceptible to all four antibiotics and 30 were resistant to at least one of them. Tests were repeated in cases of discrepant results. When each drug/strain combination was considered separately, the overall agreement between the two methods was 96.5% (98.4% for streptomycin, 95.3% for isoniazid, 96.9% for rifampicin and 95.3% for ethambutol) with regard to the initial testing and 98.8% (100, 98.5, 98.5 and 98.4%, respectively) after repeated testing. When the results were considered strain by strain, the agreement was 86% after the initial testing and 95% after repeated testing. The results were obtained after a mean time of 9.5 days. These results suggest that the Mycobacterial Growth Indicator Tube is a reliable method for testing susceptibility of mycobacterial strains to first-line antituberculous drugs. PMID- 11205632 TI - Streptococcus suis meningitis, a poacher's risk. AB - Streptococcus suis infection is a zoonosis that has been mainly reported in pig rearing and pork-consuming countries. The most common disease manifestation is meningitis, often associated with cochleovestibular signs. The causative agent is Streptococcus suis serotype 2, found as a commensal in the tonsils of its natural host, the pig. Persons at risk are mostly those with an occupational exposure to domestic pigs or their meat products. A case of meningitis caused by Streptococcus suis in a poacher who had killed and butchered a wild boar is reported. It appears that wild boar hunters are at additional risk of contracting the disease. PMID- 11205633 TI - A case of septicemia with Pediococcus acidilactici after long-term antibiotic treatment. AB - Presented here is a case of septicemia caused by an uncommon, multiresistant, gram-positive microorganism (Pediococcus acidilactici) after long-term antibiotic treatment. Pediococcus spp. are rarely cultivated from clinical specimens, and species differentiation is difficult due to the paucity of phenotypic traits. In this case, a polyphasic approach consisting of phenotypic and molecular genetic analyses was used, and the identification of Pediococcus acidilactici was conclusive. Precise identification and antimicrobial susceptibility testing of rarely isolated bacteria are required in order to provide adequate treatment to infected patients and to determine the pathogenic role of these organisms. PMID- 11205634 TI - Chronic cystitis caused by Corynebacterium urealyticum detected by polymerase chain reaction. AB - The case of a 73-year-old man with chronic cystitis due to Corynebacterium urealyticum was complicated by hematuria and urinary stone formation. The diagnosis was based on an amplification product obtained using polymerase chain reaction for mycobacterial species on urine and a bladder biopsy specimen. A specific 212 bp amplification fragment that did not hybridize with a Mycobacterium-specific probe was recognized. Sequence analysis of the fragment revealed Corynebacterium urealyticum. Routine urine cultures were negative, but prolonged culture on sheep blood agar led to the isolation and identification of Corynebacterium urealyticum. Identification was confirmed by polymerase chain reaction on the colonies. The patient was treated successfully with vancomycin. Integration of molecular laboratory diagnostics with conventional microbiology and pathology was synergistic for the diagnosis. PMID- 11205635 TI - Characterization of epidemic and nonepidemic methicillin-resistant Staphylococcus aureus strains in a university hospital in northeast Germany. AB - The aim of this study was to analyze methicillin-resistant Staphylococcus aureus strains isolated during a 1-year period by means of pulsed-field gel electrophoresis, resistance phenotyping and determination of biochemical features. Eight different resistance phenotypes with the predominant resistance type Pen Oxa Cip (penicillin, oxacillin, ciprofloxacin) were observed. None of the strains tested exhibited decreased susceptibility to vancomycin, but two strains were resistant to mupirocin. Genetic relatedness of methicillin-resistant Staphylococcus aureus isolates could be shown for two outbreaks, one of which was caused by a clone with an epidemic potential concerning duration of colonization/infection of patients and dissemination of the strains in the hospital. PMID- 11205636 TI - Screening for antimicrobial resistance in normal bacterial flora of the skin using the replica plating method. AB - The replica plating method was evaluated for detection of the antimicrobial resistance of normal bacterial flora of the skin and was compared with the results of a ten-colony method. If > or = 10% of the colonies from the master plate grew on a plate containing an antibiotic, the sensitivity of replica plating was comparable to that of a ten-colony method for samples containing resistant bacteria. However, this method classified significantly more samples as resistant to all eight antibiotics tested if the detection breakpoint was lowered to > or = 1% of the original colonies. Replica plating is an effective and practical tool for screening skin flora for resistance, also in samples with a low proportion of resistant strains. PMID- 11205637 TI - Validity of prior absorption of serum samples with Reiter's spirochetes in serological diagnosis of Borrelia burgdorferi infections. AB - Evidence of Borrelia burgdorferi sensu lato infection was sought in 230 patients with positive antibody titres in an indirect immunofluorescence test that became negative after serum samples were preabsorbed with treponemal antigen. Infection could be excluded in 82.2% (189/230) of patients, was questionable in 6.9% (16/230), and was judged to have occurred in 10.9% (25/230), including four (1.7%) cases of early, acute disease that required treatment. The preabsorption procedure clearly reduces the frequency of false-positive reactions; however, there is a definite risk of overlooking active infections with this technique. PMID- 11205638 TI - Detection of Bartonella henselae and Afipia felis DNA by polymerase chain reaction in specimens from patients with cat scratch disease. AB - Polymerase chain reaction (PCR) amplification and colorimetric identification of amplicons were performed to detect Bartonella henselae and Afipia felis DNA in specimens from patients who were clinically and histologically suspected of having cat scratch disease. PCR products were revealed using 2% ethidium bromide agarose-gel electrophoresis and identified with specific probes in a commercial colorimetric hybridization assay (DEIA) (GEN-ETI-K; DiaSorin, Italy). Six paraffin-embedded lymph node biopsies from 18 patients as well as 18 samples of peripheral whole blood and 18 sera were investigated. Bartonella henselae DNA was recovered from the whole blood of four patients, and Bartonella henselae and Afipia felis DNA were detected in one patient's lymph node biopsy. This study suggests that PCR-DEIA is sufficiently sensitive to be considered feasible for the molecular diagnosis of cat scratch disease. PMID- 11205639 TI - Puumala and Dobrava hantaviruses causing hemorrhagic fever with renal syndrome in Estonia. PMID- 11205641 TI - A case of disseminated infection with Pichia ohmeri. PMID- 11205640 TI - Successful treatment of multidrug-resistant Acinetobacter baumannii meningitis with intravenous colistin sulfomethate sodium. PMID- 11205642 TI - Rhabdomyolysis and Salmonella enteritidis infection. PMID- 11205643 TI - Hospital outbreak of methicillin-resistant Staphylococcus aureus followed by an in vivo change to a mecA-negative mutant with loss of epidemicity. PMID- 11205644 TI - Endoscopic management of bile duct stones. AB - The advantages of endoscopic retrograde cholangiopancreatography (ERCP) over open surgery make it the predominant method of treating choledocholithiasis. Today, technologic advances such as magnetic resonance cholangiopancreatography and laparoscopic surgery are challenging ERCP's primacy in the management of common bile duct (CBD) stones. This article reviews the current status of endoscopic treatment of biliary stones and examines this in relation to laparoscopic management. The techniques and safety of endoscopic sphincterotomy and balloon sphincteroplasty are reviewed. Balloon sphincteroplasty should be limited to study protocols because of safety questions and inherent limitations. After sphincterotomy, 85% to 90% of CBD stones can be removed with a Dormia basket or balloon catheter. These techniques are described as having both advantages and disadvantages. Methods for managing "difficult stones" include mechanical lithotripsy, intraductal shock wave lithotripsy, extracorporeal shock wave lithotripsy, chemical dissolution, and biliary stenting. These approaches are presented along with data supporting their use in specific situations. Laparoscopic cholecystectomy has emerged as the preferred alternative to open cholecystectomy. Parallel advances in the endoscopic and laparoscopic management of CBD stones have made the issue regarding the optimal treatment strategy complex. Three approaches to the management of choledocholithiasis in the laparoscopic era are presented as follows: strict therapeutic splitting, flexible therapeutic splitting, and strict laparoscopic management. The optimal approach needs to be defined in prospective comparative trials. For now, preoperative endoscopic stone extraction should still be recommended as the approach of choice in patients suspected to have CBD stones based on clinical, biochemical, and imaging parameters. Primary laparoscopic evaluation and management is reasonable in patients who have a low-to-moderate probability of having CBD stones. PMID- 11205645 TI - Efficacy of endoscopic isotonic saline-epinephrine injection for the management of active Mallory-Weiss tears. AB - Therapeutic endoscopy with isotonic saline-epinephrine (ISE) injection is a convenient and widely used procedure for hemostasis in upper gastrointestinal bleeding. We retrospectively evaluated 36 patients (from January 1996 to April 1999) who had been diagnosed with recent or active bleeding due to Mallory-Weiss tears in emergency endoscopic examination. The endoscopic hemostatic method with ISE injection was performed in 15 of 36 patients. The other 21 patients received conservative treatment with hemodynamic support. Patient's clinical data, laboratory data, transfusion requirements, endoscopic findings, and length of hospital stays were evaluated. Initial hemoglobin was significantly lower in the ISE group than the conservative treatment group (9.74 +/- 2.86 g/dL vs. 12.57 +/- 2.80 g/dL, respectively; p < 0.01). Mean transfusion requirements were significantly higher in the ISE group than the conservative treatment group (7.26 +/- 8.78 units vs. 2.85 +/- 6.21 units, respectively; p < 0.1). Patients in the ISE group were supposed to be having a more severe bleeding episode. Most patients achieved initial hemostasis in the ISE group and the conservative treatment group (93% and 95%, respectively). The rebleeding rate was also similar in both groups (1 in 15 in the ISE group and I in 21 in the conservative treatment group). There was no significant difference in length of hospital stay and rebleeding between these two groups (3.47 +/- 1.92 days vs. 2.47 +/- 1.47 days, respectively: p = 0.89). The endoscopic ISE injection is an inexpensive, simple, convenient therapeutic method and it can achieve initial hemostasis for active Mallory-Weiss tears. PMID- 11205646 TI - Autoantibody profile in progressive systemic sclerosis as markers for esophageal involvement. AB - We investigated the relationship between the severity and extent of esophageal involvement in patients with progressive systemic sclerosis (PSS) and the autoantibody profile. We studied 37 consecutive patients with PSS and compared their results to 25 healthy volunteers. Patients with PSS were separated into three subgroups: group 1 (antinuclear antibody [ANA] [+/-], anti-Sc170 antibody [Scl70] [-], and anticentromere antibody [ACA] [-]), group 2 (ANA [+], Scl70 [+], and ACA [-]), and group 3 (ANA [+], Scl70 [-], and ACA [+]). The lower esophageal sphincter pressure and the mean proximal esophageal amplitude were significantly lower in group 3 when compared with group 1, group 2, and the healthy controls. Distal esophageal aperistalsis was noted in 85% of group 3, 40% of group 2, and 30% of group 1. An involvement of esophageal motility was found in 100% of the patients with ACA. Our results suggest that esophageal involvement is more pronounced in patients with PSS with ACA as compared with patients with only Sc170 or ANA. PMID- 11205647 TI - Can symptoms predict esophageal motor function or acid exposure in gastroesophageal reflux disease? A comparison of esophageal manometric and twenty four-hour pH parameters in typical and extraesophageal gastroesophageal reflux disease. AB - It has been suggested that patterns of esophageal motor function and acid exposure may differ between those patients with gastroesophageal reflux disease (GERD) with classic symptoms and those with extraesophageal manifestations. Our objective was to compare various parameters of esophageal motility and acid exposure between groups of patients who had presented with extraesophageal manifestations of GERD alone, a combination of classic and extraesophageal manifestations, or classic GERD symptoms alone. A retrospective review of consecutive patients undergoing esophageal manometry and 24-hour dual-channel esophageal pH testing was performed. Information on patient demographics, symptoms, and results of various manometric and pH testing parameters was examined. We evaluated 84 patients: 32 with extraesophageal symptoms alone, 24 with both classic and extraesophageal symptoms, and 28 with classic symptoms alone. Apart from a trend toward less supine acid exposure in those with extraesophageal symptoms alone, no significant differences were evident among the three patient groups in any of the other parameters of proximal or distal esophageal acid reflux. With respect to motility parameters, lower esophageal sphincter pressure was lower in those with combined symptoms; otherwise, manometric findings were similar in the three patient groups. Our data do not support the hypothesis that the nature of the clinical presentation of GERD, whether in the form of classic or extraesophageal manifestations, is related to differing patterns of esophageal motor function or esophageal acid exposure. PMID- 11205648 TI - Prednisone withdrawal followed by interferon alpha for treatment of chronic hepatitis C infection: results of a randomized controlled trial. AB - Immunosuppressive therapy increases levels of hepatitis C virus (HCV) RNA, and when combined with interferon, corticosteroids have been reported to variably improve or have no effect on sustained response rates. We conducted a randomized double-blind placebo-controlled trial in 39 patients with biopsy-proven chronic HCV infection and elevated alanine aminotransferase levels. Patients received either 6 weeks of a tapering dose of prednisone (60 ng, 40 mg, and 20 mg in 2 week intervals) or an identical placebo. All patients then received recombinant interferon alpha-2b, 3 million units three times a week for 24 weeks. Patients were then followed for a further 24 weeks. At the end of the study there was no significant difference in the sustained biochemical response rates between the two groups (4/20 vs. 3/19, p value was not significant). Prednisone-treated patients had a significant increase in HCV RNA from baseline during steroid treatment (400 +/- 60% increase vs. -280 +/- 140% decrease; p = 0.005). Two prednisone-treated patients were withdrawn from the study secondary to serious complications related to therapy. Prednisone priming before interferon alpha therapy in patients with chronic HCV infection does not improve the sustained response rate. This therapy was associated with an increase in viral burden and significant morbidity. PMID- 11205650 TI - A randomized, controlled trial of interactive, multimedia software for patient colonoscopy education. AB - The purpose of our study was to assess the effectiveness of computer-assisted instruction (CAI) in patients having colonoscopies. We conducted a randomized, controlled trial in large, multispecialty clinic. Eighty-six patients were referred for colonoscopies. The interventions were standard education versus standard education plus CAI, and the outcome measures were anxiety, comprehension, and satisfaction. Computer-assisted instruction had no effect on patients' anxiety. The group receiving CAI demonstrated better overall comprehension (p < 0.001). However, Comprehension of certain aspects of serious complications and appropriate postsedation behavior were unaffected by educational method. Patients in the CAI group were more likely to indicate satisfaction with the amount of information provided when compared with the standard education counterparts (p = 0.001). Overall satisfaction was unaffected by educational method. Computer-assisted instruction for colonoscopy provided better comprehension and greater satisfaction with the adequacy of education than standard education. Computer-assisted instruction helps physicians meet their educational responsibilities with no decrement to the interpersonal aspects of the patient-physician relationship. PMID- 11205649 TI - Lack of association between Helicobacter sp colonization and gallstone disease. AB - Recently, Helicobacter sp has been identified in resected gallbladder tissue and in collected bile from Chilean patients with chronic cholecystitis. Therefore, it an association between bile Helicobacter sp and gallbladder cancer has been proposed. Interestingly, both Helicobacter colonization and gallstone disease (GD) happen very frequently in Chile. However, whether there is an association between Helicobacter colonization and GD has not been completely studied. The aim of this study was to determine the incidence of Helicobacter in human gallbladder tissues with GD. The study included 95 Mexican patients undergoing cholecystectomy. Collected gallbladder specimens were assessed to identify Helicobacter sp using histology, immunohistochemistry, and polymerase chain reaction (PCR) analysis using Helicobacter-specific 16-S ribosomal RNA primers. Of the 95 specimens examined in detail, all had stones as follows: 56 (59%) had chronic cholecystitis; 7 (7.4%), acute cholecystitis: 15 (16%), both chronic and acute cholecystitis, 10 (9.5%), cholesterolosis, and 7 (7.4%), lymphoid hyperplasia. Specimens were considered positive for Helicobacter when histology was positive. Only 1 of the 95 specimens was positive for Helicobacter by immunohistochemistry analysis; 1 of 32 cases, by PCR. These results suggest a low incidence of Helicobacter in the gallbladder epithelium of Mexican patients with GD. However, we can not discard the existence of uncommon Helicobacter sp in gallbladder epithelium and its association with gallstone pathogenesis. Additionally, this study suggests no apparent association between GD and Helicobacter colonization in a Mexican population. PMID- 11205651 TI - Vaccination, screening for malignancy, and health maintenance of the liver transplant recipient. AB - Transplant recipients are highly motivated to maintain their recovered health status and are generally compliant with pharmacotherapy and medical follow-up. As well as routine blood tests and monitoring of immunosuppressant drug levels, recipients require immunization updates and regular screening for malignancy, diabetes, hypertension, hyperlipidemia, and ophthalmologic complications. Little information is available about the consistent implementation of these health maintenance strategies in this population. A telephone survey of liver transplant recipients was conducted using a 20-item questionnaire. It was designed to assess the frequency and adequacy of health maintenance screening, immunizations, and screening tests for malignancy, which are specific to the liver transplant population. We contacted 60 liver recipients transplanted at our institution between 1992 and 1996. The mean age of the patients (31 men and 29 women) was 48 years (range, 42-56 years). Before transplantation, pneumococcal and hepatitis B vaccination occurred in 13% and 18%, respectively. After transplantation, 27% had received pneumococcal vaccination and none had received primary vaccination for hepatitis B. Forty-eight percent received yearly influenza vaccination. Of 60 questioned recipients, 2 were aware of their varicella exposure status or a possible need for varicella immunoglobulin if a primary exposure to chickenpox were to occur. Two were aware of the need for the recipient's children or grandchildren who were undergoing polio vaccination to receive an inactivated intramuscular polio preparation. Yearly screening for dermatologic or oral malignancies was provided to only 40% of patients. Physician-performed breast examination or screening mammograms was done in 38% of the surveyed women. Eleven percent of the women had received a gynecologic examination with a cervical cytologic examination within the prior 2 years. Of the male recipients, 68% received either digital prostate examination or serum prostate specific antigen determinations or both. Of 60 recipients, 30 had had either flexible sigmoidoscopy or colonoscopy within the previous 2 years. Yearly dental examinations were performed on 75% of patients, and more than 90% had at least yearly blood pressure and weight determinations. Of 60 patients, 41 were aware of cholesterol and lipid profiles having been performed within the past 2 years. Ophthalmologic screening was performed in 83% of surveyed recipients. This survey suggests that routine health maintenance management is less than optimal in this population. Follow-up based on a standard protocol may improve the health care of these patients. PMID- 11205652 TI - Features of recurrent primary sclerosing cholangitis in two consecutive liver allografts after liver transplantation. AB - Recurrence of primary sclerosing cholangitis (PSC) after liver transplantation is very uncommon. The true incidence of recurrence is unknown, mainly because of the difficulty in differentiating ischemic strictures from that of recurrent disease. Primary sclerosing cholangitis and ischemic strictures have identical histopathologic and cholangiographic features. We report a young man who had recurrence of PSC in two allografts and report our experience in 32 patients who had liver transplantation for PSC. Six patients (18%) had evidence of non anastomotic strictures and, of these, only one patient (reported here) had unequivocal evidence of true recurrence. The strictures in other five patients happened because of ischemia. The recurrence of the disease in two allografts in an immunosuppressed patient, in the absence of ischemia, chronic rejection, or any known pathogen, raises the question of the role of an unidentified infectious agent in the etiopathogenesis of PSC. PMID- 11205653 TI - Bochdalek's hernia in adults. AB - Bochdalek's hernia is a congenital hernia of the diaphragm, which is manifested in the early years of life. Its diagnosis is difficult and is based on barium studies. We present an adult patient with Bochdalek's hernia who exhibited a gastric volvulus. The patient had a history of intermittent abdominal pains. In this article, we analyze the diagnostic and therapeutic procedures, laying special emphasis on the importance of early diagnosis in the prevention of complications. PMID- 11205654 TI - Fatal bleeding from a residual vein at the esophageal ulcer base after successful endoscopic variceal ligation. AB - Endoscopic variceal band ligation (EVL) is now one of the accepted treatment options for esophageal varices, and the safety of this procedure has been proved. However, we experienced a patient who had a fatal massive bleeding after successful EVL for ruptured esophageal varix. Postmortem study revealed a residual vein at the base of the esophageal ulceration associated with the ligation, which was believed to be the site of the fatal bleeding. His platelet counts and prothrombin time were not very impaired. Our case indicates that fatal massive bleeding can occur in patients after successful EVL without specific risk factors and indicates the importance of the awareness of the possibility of these complications. PMID- 11205655 TI - Amyloidosis-induced gastrointestinal bleeding in a patient with multiple myeloma. AB - We present a case of multiple myeloma (MM) complicated by recurrent amyloidosis induced gastrointestinal bleeding. The patient presented with episodes of coffee ground vomitus or massive hematochezia. No bleeding focus could be identified using endoscopy, a red blood cell scan, or angiography. Finally, a tissue biopsy taken at the irregular mucosa beside protruding vessels in the duodenum confirmed the diagnosis of gastrointestinal amyloidosis. As this case illustrates, the absence of systemic symptoms of amyloidosis and nonspecific endoscopic findings in gastrointestinal amyloidosis may make diagnosis difficult. Therefore, we recommend that a diagnosis of amyloidosis-induced gastrointestinal bleeding should be considered in patients with MM with an obscure hemorrhage. PMID- 11205656 TI - Intravascular stent implantation of the celiac artery in the treatment of chronic mesenteric ischemia. AB - We report a case of chronic mesenteric ischemia that caused abdominal angina and weight loss in an 80-year-old woman. A mesenteric angiogram revealed total occlusion of the superior mesenteric artery and 90% stenosis of the celiac and inferior mesenteric arteries. Balloon angioplasty of the celiac artery failed because of elastic recoil. A 15-mm Palmaz-Schatz stent was dilated to 6 mm in the proximal celiac artery with an excellent angiographic result and complete resolution of symptoms. A clinical, 1-year follow-up demonstrated success with no recurrence of pain. This case report illustrates the value of balloon dilatation and stent implantation in a patient with atherosclerotic narrowing of multiple abdominal visceral arteries. PMID- 11205657 TI - Anasarca and small bowel obstruction secondary to endometriosis. AB - Intestinal involvement by endometriotic tissue occurs in up to 37% of patients with endometriosis. The vast majority of patients do not experience symptoms related to the gastrointestinal tract. In particular, the complications of intestinal obstruction and malabsorption secondary to endometriosis are exceedingly uncommon. We present a 42-year-old woman with intestinal obstruction, protein-losing enteropathy, and anasarca secondary to endometriosis. She had a 1 year history of watery diarrhea, bloating, and abdominal pain with a 30-lb weight loss over 3 months. She had no previous history of endometriosis, and laboratory investigations showed severe hypoalbuminemia, hypokalemia, and metabolic acidosis. Abdominal x-rays revealed air-fluid levels and dilated loops of small bowel. She underwent surgical resection with primary anastomosis. Pathologic evaluation showed extensive endometriosis of the small bowel and appendix, which resulted in complete obstruction. Segments of ileum also demonstrated moderate-to marked blunting of the villi. Postoperatively, the patient had a slow recovery with resolution of anasarca and a gradual increase in her weight. This report illuminates the rare, yet significant, complications of intestinal endometriosis, including small bowel obstruction, the development of a protein-losing enteropathy, and anasarca. One should consider the possibility of intestinal endometriosis in the differential diagnosis of bowel obstruction in women of childbearing age. PMID- 11205658 TI - Ulcerative duodenitis accompanying ulcerative colitis. AB - Ulcerative colitis (UC) is a chronic inflammatory disease of the colon of unknown etiology. There are varied manifestations in the natural course of UC. However, duodenum is not generally considered a target organ of UC. Here, we report two patients with steroid-responsive ulcerative duodenitis with colitis that was consistent with UC, but not with Crohn's disease. We also reviewed six cases of ulcerative duodenitis with UC. Duodenal lesion with UC may be a more common phenomenon, although infrequently clinically manifested under steroid therapy. Upper gastrointestinal tract inflammation in UC warrants further studies to ascertain whether the duodenum is a target organ in UC, especially in steroid free conditions. PMID- 11205659 TI - Interstitial nephritis in patients with inflammatory bowel disease treated with mesalamine. AB - Mesalamines are slow-release formulations of 5-aminosalicylic acid (5-ASA) and are effective as primary treatment and maintenance therapy in inflammatory bowel disease. Interstitial nephritis is a recognized side effect. We report two cases of biopsy-confirmed interstitial nephritis in patients being treated with 5-ASA. Both had a trial of steroid therapy. One patient had partial recovery of renal function but the other patient was in chronic renal failure and likely was approaching the need for dialysis. Interstitial nephritis is an under-recognized complication of 5-ASA therapy. Early identification and withdrawal of this drug can lead to a partial or complete reversal of renal dysfunction. PMID- 11205660 TI - A pregnant woman with hepatitis A and Guillain-Barre. AB - Guillain-Barre syndrome (GBS) is often preceded by an infectious disease. A case of GBS after hepatitis A in a pregnant woman is described. The patient was treated with intravenous immunoglobulin and had full recovery with no neurologic sequelae. She gave birth in term to a healthy baby. This is the first reported case in the English literature of a triple condition of hepatitis A, GBS, and pregnancy. PMID- 11205661 TI - Hepatic sarcoidosis with vanishing bile duct syndrome, cirrhosis, and portal phlebosclerosis. Report of an autopsy case. AB - A few cases of sarcoidosis are associated with progressive liver disease, with a wide variety of clinicopathologic features. Herein, we report an autopsy case (65 year-old man). During an examination for liver dysfunction, cirrhosis with cholestatic dysfunction and splenomegaly were found. Needle liver biopsy revealed cirrhosis with lymphocytic piecemeal necrosis, dense septal fibrosis, and ductopenia. In addition, noncaseating epithelioid granuloma was also seen in the periportal region. Ductal enzymes and immunoglobulin M (IgM) levels were elevated, although antimitochondrial antibodies were negative. Instead, angiotensin-converting enzyme was elevated. He died of pulmonary failure and lung cancer. The autopsy liver (1,220 g) showed multinodular cirrhosis with broad and dense septa that divided the parenchyma. Mild lymphoid cell infiltration was seen in the periportal region. About a half of the interlobular bile ducts were lost, and the remaining bile ducts showed prominent periductal fibrosis, resembling sclerosing cholangitis. Interestingly, a few interlobular bile ducts showed chronic nonsuppurative cholangitis with epithelioid granulomas. Intrahepatic portal veins showed luminal narrowing with prominent phlebosclerosis. Hepatobiliary pathologies that resemble primary biliary cirrhosis and primary sclerosing cholangitis and that are followed by vanishing bile duct syndrome, chronic active hepatitis-related cirrhosis, and intrahepatic portal venous phlebosclerosis occur in a single case of sarcoidosis. PMID- 11205662 TI - Ulcerative duodenitis with ulcerative colitis: is it Crohn's disease or really ulcerative colitis? PMID- 11205663 TI - Look out for toxic effects of mesalamines! PMID- 11205664 TI - Surveillance issues in inflammatory bowel disease: ulcerative colitis. AB - This review article on the surveillance of patients with ulcerative colitis provides an overview of the criteria for evaluating screening and surveillance programs and applies the criteria to the available evidence to determine the effectiveness of the surveillance of patients with ulcerative colitis. We examine the clinical outcomes associated with surveillance, the additional clinical time required to confirm the diagnosis of dysplasia and cancer, compliance with surveillance and follow-up, and the effectiveness of the individual components of a surveillance program, including colonoscopy and pathologist's interpretation. The disability associated with colectomy is considered, as are the cost and acceptability of surveillance programs. Patients with long-standing ulcerative colitis are at risk for developing colorectal cancer. Recommended surveillance colonoscopy should be supported. New endoscopic and histopathologic techniques to improve the identification of high-risk patients may enhance the effectiveness and cost-effectiveness of surveillance practices. PMID- 11205665 TI - ERPET training course: establishment of reference levels in diagnostic radiology. European Radiation Protection, Education and Training. PMID- 11205666 TI - Endothelin: what does the radiologist need to know? AB - Endothelin (ET) is a potent endogenous vasoconstrictor peptide. It has been implicated in various pathological states since its discovery in 1988. The cardiovascular system and the kidneys are important sites for the action of this peptide. Two types of ET receptor, ETA and ETB, govern the biological effects of ET. Drugs that can prevent the endogenous synthesis of ET or block its binding to receptors may offer important therapeutic impact to patients with congestive heart failure, pulmonary hypertension and acute renal failure. Areas of particular interest to the radiologist include the role of ET in mediating some of the side effects of contrast media, particularly contrast medium nephropathy, and the involvement of ET in the pathogenesis of restenosis following angioplasty. This review outlines the basic biology of this important mediator and its role in health and disease. PMID- 11205667 TI - Growth rate of small lung cancers detected on mass CT screening. AB - CT has recently been used in mass screening for lung cancer. Small cancers have been identified but the growth characteristics of these lesions are not fully understood. We identified 82 primary cancers in our 3-year mass CT screening programme, of which 61 were examined in the present study. The volume doubling time (VDT) was calculated based on the exponential model using successive annual CT images or follow-up CT images. All cases were also examined in the hospital by high resolution CT (HRCT). Lesions were divided into three types based on HRCT characteristics: type G (n = 19), ground glass opacity (GGO); type GS (n = 19), focal GGO with a solid central component; and type S (n = 23), solid nodule. 18 (95%) lesions of type G, 18 (95%) of type GS and 7 (30%) of type S were invisible on conventional chest radiographs. The mean size of the tumour was 10 mm, 11 mm and 16 mm for type G, type GS and type S, respectively. Most tumours (80%) were adenocarcinomas; 78% of these were GGO (type G and GS). Mean VDT values were 813 days, 457 days and 149 days for type G, type GS and type S, respectively; these are significantly different from each other (p < 0.05). Our results show that annual mass screening CT for 3 successive years resulted in the identification of a large number of slowly growing adenocarcinomas that were not visible on chest radiographs. PMID- 11205668 TI - Upper retropharyngeal node involvement in differentiated thyroid carcinoma demonstrated by 131I scintigraphy. AB - We report four patients with papillary thyroid cancer who had upper retropharyngeal node involvement demonstrated by 131I scintigraphy. Three patients presented with a thyroid nodule and enlarged jugular nodes. Total thyroidectomy was performed with node dissection. Pathology demonstrated papillary carcinoma with several metastatic nodes. 131I scanning 4 weeks after surgery demonstrated increased uptake in an upper retropharyngeal node. In one patient, thyroidectomy had been performed 21 years previously. Increased thyroglobulin level led to 131I scanning, which showed focal retropharyngeal uptake. All four patients had asymmetrical uptake at mouth level with focal uptake close to the sagittal plane. A lateral projection showed focal uptake between the base of the skull and the mandibular angle, behind the region of the mouth and nose. CT in all cases and MRI in one case confirmed the presence of an enlarged node. The mass was removed surgically in two patients and pathology confirmed the papillary nature of the metastatic node. Two patients were treated by 131I. Focal uptake of 131I in the region of the mouth is ambiguous, since salivary uptake of 131I is a common finding on scintigraphy. In cases of asymmetrical uptake in the region of the mouth, a lateral projection of the head therefore allows the correct diagnosis. PMID- 11205669 TI - The usefulness of orbital lines in detecting blow-out fracture on plain radiography. AB - The purpose of this study was to assess the diagnostic value of orbital line changes on plain radiographs in detecting blow-out fracture. 92 cases of surgically confirmed blow-out fracture were retrospectively analysed in regard to plain radiographs and CT. Anterior and posterior lamina papyracea lines (ALPL and PLPL, respectively) of the orbital medial wall as well as the posteromedial floor line (PMFL) were assessed on orbital posteroanterior projections. The inferomedial orbital line (IMOL) and the inferior wall line were assessed on Waters projections. Orbital lines on plain radiographs were compared with CT findings. Of 53 cases of lamina papyracea fracture, 47 cases showed orbital line changes on plain radiographs (sensitivity 88.7%). Changes of PLPL (41/47), IMOL (29/47), ALPL (4/47) and PMFL (2/47) were demonstrated as depression, loss, discontinuity and irregularity. In four cases showing normal radiographs, the fractures measured less than 9 mm in size on CT. All 25 cases with orbital floor fracture accompanying medial wall fracture demonstrated orbital line changes of PMFL (16/25), PLPL (14/25), ALPL (3/25) and IMOL (2/25) (sensitivity 100%). 12 of 14 cases with orbital floor fracture demonstrated changes of inferior wall line (7/12) and PMFL (6/12) (sensitivity 85.7%). Two cases demonstrated asymmetric focal soft tissue density without orbital line changes. Orbital line changes on plain radiographs corresponded well with CT findings, confirming the usefulness of plain radiographs in detecting blow-out fracture. PMID- 11205670 TI - The vascular manifestations of Behcet's disease: angiographic and CT findings. AB - The purpose was to evaluate angiographic and CT manifestations of vascular Behcet's disease. The medical records of 64 patients with Behcet's disease, treated in our hospital during the last 4 years, were reviewed. 37 patients underwent angiography or CT in the symptomatic regions because of symptoms or clinical signs of vascular involvement by Behcet's disease. 33 (male:female ratio 28:5; mean age 35 years) of the 37 patients demonstrated vascular involvement, which was surgically proven (18 patients) or diagnosed on angiography (15 patients). Angiograms and CT images of these 33 patients were retrospectively analysed for lesion type, location, extent and other characteristic findings of vascular involvement. 12 patients had only venous lesions, 11 had only arterial lesions and 10 had both arterial and venous lesions. The major angiographic findings of vascular Behcet's disease were acute or chronic thrombosis in deep veins of the lower extremities (19 patients), in the inferior vena cava (4 patients) and in the superior vena cava (2 patients), pseudoaneurysms of large or medium sized arteries (11 patients), and occlusions/ stenoses of distal run-off arteries (13 patients). Common CT findings were obliterated deep veins (8 patients) and non-calcified thickened aneurysmal walls (9 patients), with or without contrast enhancement. The combination of these angiographic and CT findings with clinical manifestations are helpful in distinguishing vascular Behcet's disease from other vasculitides. PMID- 11205671 TI - Non-tumorous enhancement caused by cholecystic venous inflow shown on biphasic CT hepatic arteriography: comparison with hepatocellular carcinoma. AB - The haemodynamics in non-tumorous abnormalities on CT arterial portography (CTAP) owing to cholecystic venous direct inflow to the liver were compared with the haemodynamics in hepatocellular carcinoma. 53 patients who simultaneously underwent CTAP and CT during hepatic arteriography (CTHA) to detect hepatocellular carcinoma had the late phase added to CTHA. Changes in size, shape and pattern of 47 non-tumorous enhancement abnormalities on the liver around the gall bladder or in the dorsum of segment IV between the early and late phases on biphasic CTHA as well as of 60 tumorous lesions were determined. Enhancement on biphasic CTHA was seen in all 47 lesions with a non-tumorous portal defect (early phase alone, n=8; late phase alone, n = 3; both, n = 36). In these 47 lesions, the size and the shape of enhancement changed in 63.8% and 51.1%, respectively, between the early and late phases on CTHA; the pattern of enhancement did not change in 72.3%. On the other hand, the size of enhancement on biphasic CTHA changed in only 16.7% of 60 tumours, and the shape in only 5%, although the enhancement pattern changed in a large proportion (80%). In conclusion, owing to the difference in haemodynamics, non-tumorous abnormalities caused by cholecystic venous inflow and tumours are clearly delineated on biphasic CTHA. Thus, adding the late phase to previous single phase CTHA (i.e. performing biphasic CTHA) is useful in differentiating the two entities. PMID- 11205672 TI - Evaluation of a technique for estimation of extraocular muscle volume using 2D MRI. AB - Measurements of extraocular muscle volume may be useful as an outcome indicator in the assessment of treatment options in thyroid-associated ophthalmopathy. In this study, a technique for estimating extraocular muscle volume from two dimensional T1 weighted MR images acquired in the coronal plane is described. For each image slice, the cross-sectional area of individual extraocular muscles was estimated using a combination of semi-automated outlining based on a local thresholding technique and manual outlining where thresholding was not possible. The technique was assessed using three sets of images: a computer-generated virtual image set with "extraocular muscles" of known volumes; a set of images from 19 biochemically and clinically euthyroid patients; and images from 7 patients with thyroid-associated ophthalmopathy. From the computer-generated images, the accuracy was determined as 7.6%. Intraobserver agreement was investigated using repeated MRI scans on a single subject and repeat outlining of muscles on five sets of images from different subjects. The mean difference between repeat measurements was 2% (SD 5.9%). We conclude that two-dimensional MR images can be used to determine changes in muscle volume of greater than 12% during treatment of thyroid-associated ophthalmopathy. PMID- 11205673 TI - Effect of a full and empty bladder on radiation dose to the uterus, ovaries and bladder from lumbar spine CT and X-ray examinations. AB - This is a quantitative study of the effect of a full and empty bladder on the position of the uterus, ovaries and bladder relative to the lumbar spine. Data are used to estimate the difference in radiation dose to these organs from performing a lumbar spine CT investigation or a lateral lumbar spine radiograph with a full bladder compared with an empty bladder. 12 women of child-bearing age underwent pelvic magnetic resonance scans with full and empty bladders. The positions of the uterus, ovaries and bladder were matched with the radiation dose distribution that would have occurred either side of the inferior boundary of the CT scan volume and the lateral lumbar spine radiograph. These radiation dose profiles were measured on phantoms using a combination of ionization chambers and thermoluminescent dosemeters. When the bladder was emptied, the mean position of the endometrial cavity fundal tip moved from 4.1 cm to 6.1 cm inferior to the centre of the L5/S1 disc space, and from 0.87 cm to 1.12 cm anterior to the centre of the L5/S1 disc space. This movement on micturation would have reduced the mean dose to the uterine internal fundal tip during a pelvic CT scan from 6.8 mGy to 3.9 mGy, which represents a mean reduction of 43% (range 12-67%). The mean dose from a lateral lumbar spine examination would have been reduced from 197 microGy to 126 microGy. The change in ovary position results in the mean ovary dose being reduced by 48% for the lumbar spine CT scan and by 43%) for a lateral lumbar spine radiograph. When the bladder was emptied, the average position of the bladder wall moved from 7.2 cm to 10.3 cm inferior to the L5/S1 disc space. This change in bladder position reduces the mean dose to the wall of a full bladder from 5.7 mGy for a CT scan and 114 microGy for a lumbar spine radiograph to 2.2 mGy and 42 microGy, respectively, for an empty bladder. PMID- 11205674 TI - Evaluation of physical performance of a scintillation dosemeter for patient dosimetry in diagnostic radiology. AB - The physical performance of the patient scintillation dosemeter Skin Dose Monitor (SDM) was evaluated for use in diagnostic radiology. The SDM response was found to be linear, with output air kerma and output air kerma rate having a reproducibility in time lower than +/- 2.4%) (one standard deviation). A calibration protocol taking into account the more significant parameters, such as radiation quality dependence and the relative sensitivity of SDM detectors of the same batch, can be applied so that the maximum overall uncertainty is +/- 18% at the 95% confidence level. The SDM detectors did not show any loss of sensitivity during the 5-month period of evaluation. SDM performance was evaluated against thermoluminescent dosemeters (TLDs) (GR200A) by monitoring chest X-rays in 18 adult patients. The difference in entrance surface dose (ESD) values between the SDM and TLDs was less than 10%, but a lack of accuracy in ESD values of less than 0.3 mGy was observed. The main benefit of the SDM device compared with TLDs is the real-time read-out of dose combined with a better flexibility and rapidity of use for approximately the same cost per measurement. The SDM device is a good candidate for regular measurement of patient doses in diagnostic imaging departments as required under implementation of the European Council Medical Exposure Directive of 30 June 1997. PMID- 11205675 TI - Methods of measurement of image quality in teleultrasound. AB - In recent years, teleultrasound has emerged as a potentially effective method of provision of ultrasound services to remote areas of the community. Transmission of teleultrasound, however, requires a high degree of compression when utilizing the relatively low bandwidth ISDN connections available within the UK. The actual amount of compression occurring varies both with the connection and the image content, often on a frame to frame basis. For this reason, traditional measurements of image quality using test tools are ineffective. Most studies to date have assessed equipment performance by testing diagnostic performance. Although this is the most important method of assessing the results of image degradation, few studies have attempted to perform physical measurements of degradation. The aims of this study were to measure the amount of degradation within a teleultrasound system and, using a number of methods, to ascertain the most useful indicators of loss of image quality. Groups of successive abdominal ultrasound images were captured and digitized both before and after degradation via an ISDN6 teleultrasound system. Normalized mean squared error (NMSE), pixel histograms, line and surface plots, Fourier spectra and contrast measurements were carried out on regions of interest in both sets of images. The NMSE was most sensitive to degradation, with alterations in the NMSE value depending on image content and degree of degradation. Fourier analysis was also indicative, showing consistent changes in high frequency content again varying with image content. PMID- 11205676 TI - Breast radiotherapy phantom design for the START trial. START trial management group. AB - The design of phantoms for use in radiotherapy involves a number of complex issues. This paper describes breast and chest wall phantoms that have been designed and constructed for the START trial. Four phantoms have been manufactured, including two two-dimensional phantoms used on the first round of audit visits to assess the ability of departments to plan with the required accuracy. Two further phantoms have been constructed and will be used in the second round of audit visits; one is a water-filled three-dimensional phantom for investigating off-axis dosimetry, the other is to be used to assess dose in the junction region between the tangential fields and the supraclavicular fossa field. The manufacturing and design process for each of the phantoms is discussed. PMID- 11205677 TI - Treatment of a false aneurysm of an intercostal artery using a covered intracoronary stent-graft and a radial artery puncture. AB - This case report documents the successful treatment of a false aneurysm of the left internal mammary artery with a covered coronary artery stent. The advantages and disadvantages of this novel method of treatment are discussed, together with a review of alternative methods of treatment of false aneurysms. PMID- 11205678 TI - CT and DSA appearances of a ruptured congenital arteriovenous malformation of the posterior mediastinal aorta. AB - A case of symptomatic congenital arteriovenous malformation detected in an adult patient is presented. The diagnosis was not suspected clinically but was demonstrated by CT and digital subtraction angiography. Although very rare, a congenital arteriovenous malformation of the posterior mediastinal aorta could present as a catastrophic event if it ruptures. Serpiginous vascular channels in the retro-oesophageal posterior mediastinum on CT and angiography should raise the possibility of an arteriovenous malformation. PMID- 11205679 TI - Sacculation of the uterus and placenta accreta: MRI appearances. PMID- 11205680 TI - Metastasis to the male breast from carcinoma of the urinary bladder. AB - We report a case of male breast metastasis from a urothelial carcinoma. Only two cases of this type of metastasis have been previously reported, and these were in the female breast. Clinical examination showed a progressive swelling of the left mammary region, with periareolar skin infiltration. Both mammography and ultrasound showed a rounded mass. Only histological examination with immunohistochemical staining permitted the correct diagnosis to be made. A particular feature of the present case is the absence of contralateral gynaecomastia, normally seen in cases of metastatic tumour to the breast from prostatic carcinoma. PMID- 11205681 TI - Intracranial dural empyema. AB - Intracranial dural empyema is a neurosurgical emergency with potentially devastating complications. The prognosis is adversely affected by delay in diagnosis. Modern imaging techniques, especially contrast enhanced CT and MRI, have improved the speed and accuracy of radiological diagnosis of this condition, with an associated reduction in mortality. Despite this, there may still be a delay in diagnosis, partly owing to the subtlety of early radiological signs, especially on unenhanced CT. We present cases that illustrate some of the radiological manifestations, complications and potential pitfalls in diagnosis. PMID- 11205682 TI - A painful tibial lesion. PMID- 11205683 TI - Regarding X-ray leakage during radiotherapy. PMID- 11205684 TI - Limitations of randomized clinical trials. Proposed alternative designs. AB - BACKGROUND: The classical two-period crossover and two-parallel-groups designs for clinical drug trials are unable to answer many current scientific questions, and are sometimes ethically or financially difficult. For example, the classical designs do not allow the study of the effects of combined treatments and their interactions. Also, the generation of parallel data that are no more than a repetition of previous research is ethically debatable and in a sense a waste of money. Objectives are to identify what a classical clinical trial cannot manage, to summarize and discuss alternative trial designs that are helpful for such purposes. RESULTS: A classical clinical trial cannot: (i) assess combined therapies, (ii) take historical data into account, (iii) safeguard ethics and efficacy during the course of long-term trials, (iv) study drugs, before well established toxicity information is available, (v) account for the possibility of therapeutic equivalence between test and reference treatment, (vi) study multiple treatments in one trial, and (vii) adjust change scores for baseline levels. Alternative designs helpful for such purposes are respectively: (i) factorial designs, (ii) historical controls designs, (iii) group-sequential interim analysis designs, (iv) sequential designs for continuous monitoring, (v) therapeutic equivalence designs, (vi) multiple crossover-periods/multiple parallel-groups design, and (vii) increased precision designs through multivariate adjustment. Main problems include the increased risks of type I and type II errors and the loss of validity criteria. CONCLUSIONS: Non-classical trial designs are reviewed. They offer relevant scientific, ethical, and financial advantages. The increased risks of type I and type II errors should be accounted for in the design stage of the trial. PMID- 11205685 TI - Haemochromatosis: automated detection of the two point mutations in the HFE gene: Cys282Tyr and His63Asp. AB - Hereditary haemochromatosis (HH) is one of the most common inherited diseases among Caucasians. Two mutations in the HFE gene have been implicated in HH: 80 to 90% of the patients with HH are homozygous for the point mutation CYS282Tyr, while the majority of the remaining patients displays either a compound heterozygosity for the mutation CYS282Tyr and the point mutation HIS63Asp, or are homozygous for HIS63Asp. Though the disease can be treated easily, symptoms are non-specific, and onset and severity are influenced by environmental factors, and therefore the disease can remain undetected until decades of iron overload lead to irreversible damage in a variety of organs, which may result in their failure. In order to detect patients with HH, simple and cost-effective tests are needed. We have developed a rapid, automated, PCR-based test which makes use of a diagnostic restriction site in each of two amplified fragments. The test employs off-the-shelf chemistry and uses the automated detection process of an immunoassay analyzer that is available in many clinical laboratories, thus avoiding an additional investment in a more specialized PCR analyzer. Because of its low costs and easy handling, the assay is particularly suited for the routine clinical laboratories. PMID- 11205686 TI - Presence of group IIa secretory phospholipase A2 in mast cells and macrophages in normal human ileal submucosa and in Crohn's disease. AB - Secretory group IIa phospholipase A2 (PLA2-II) is an important regulator of proinflammatory lipid mediator production and may play a role in ileal inflammation in Crohn's disease. The enzyme has previously only been detected in epithelial Paneth cells. However, one characteristic feature of Crohn's disease is the transmural inflammation. Full thickness ileal sections from nine patients with Crohn's disease, and histologically normal sections from patients with colonic cancer (n=7) and chronic severe constipation (n=1) as controls, were used in this study. PLA2-II-positive cells were detected by immunofluorescence and in situ hybridization. Metachromatic staining and esterase staining were used to identify mast cells and macrophages, respectively. It was shown that mast cells and macrophages in the ileal submucosa in both patients and controls showed positive PLA2-II staining. The number of PLA2-II-labeled cells that did not react with metachromasia, e.g. macrophages, was significantly greater in inflamed Crohn's disease compared to controls. This is, to our knowledge, the first study that has described the presence in healthy, while presence and upregulation of PLA2-II-positive cells in inflamed human ileal submucosa. Our findings suggest a proinflammatory potential for secretory PLA2-II in submucosa, while proinflammatory stimulation of mast cells and macrophages in vitro has shown that the enzyme is responsible for delayed prostaglandin formation. PMID- 11205687 TI - Relationship between plasma ammonia concentration and beta-N-acetylhexosaminidase isoenzyme activities in liver cirrhosis. AB - Ammonia is known to increase the secretion of beta-N-acetylhexosaminidase (Hex) to the extracellular medium in cultured human fibroblasts and Hep G2 cells. We examined 35 patients with liver cirrhosis and the results revealed a significant increase for the plasma activities of total Hex and its isoenzymes Hex A and Hex B (p < 0.001). The partial correlations, with other biochemical markers of liver injury constant, between plasma ammonia concentration and the activity (r = 0.658) and the proportion in percentage of the Hex B isoenzyme (r = 0.692) were statistically significant (p < 0.001). The increased concentration of ammonia could explain, at least partially, an increased secretion of Hex B isoforms to the plasma in patients with liver disease. PMID- 11205688 TI - Thiol redox status influences extracellular concentration of homocysteine in HeLa cell cultures. AB - We have recently shown that low concentrations of copper ions increased the extracellular concentration of homocysteine in a HeLa cell culture system. This increase might be attributed to copper-induced oxidation of extracellular homocysteine, since earlier reports suggest that the oxidized fraction of homocysteine seems to be less available for cellular uptake than the reduced fraction. To investigate further this mechanism we have therefore, in the present study, determined intra- and extracellular concentrations of homocysteine and their relations to the extracellular thiol redox status. The results of this study show that the redox status of homocysteine is important for its extracellular concentration. Increased oxidation of thiols catalyzed by copper ions resulted in an increased extracellular concentration of homocysteine, whereas the addition of antioxidant agents (N-acetylcysteine or dithiothreitol) or a specific copper(I) ion chelator (bathocuproinedisulfonic acid) was accompanied by a decreased extracellular concentration of homocysteine. These effects are probably dependent on differences in cellular uptake between reduced and oxidized homocysteine. PMID- 11205689 TI - Serum total and lipid-bound sialic acid levels following acute myocardial infarction. AB - Although serum total sialic acid has been shown to be a cardiovascular risk factor, with elevated levels associated with increased cardiovascular mortality and also with cerebrovascular disease, the reason for the elevation in serum sialic acid content remains obscure. It has been shown that an increased output of serum proteins by the liver due to some type of acute phase reaction may be one of the possible sources of an increased serum sialic acid concentration in patients with myocardial infarction. An increase in the activity of sialidase, which cleaves the terminal sialic acid residues from oligosaccharides, glycoproteins and gangliosides, may also play an important role in the elevation of serum total sialic acid in myocardial infarction. Elevated serum total sialic acid in the blood might result either from the shedding or secreting of sialic acid from the cell membrane surface, or releasing of cellular sialic acid from the cell into the bloodstream due to cell damage after myocardial infarction. The purpose of the present study is to investigate serum total and lipid-bound sialic acid and the enzymes serum lactate dehydrogenase, creatine kinase and aspartate aminotransferase in patients with acute myocardial infarction, at 24 h post infarction (day 1), 48 h post-infarction (day 2) and 72 h post-infarction (day 3). A possible role of cell damage in the elevation of serum total and lipid bound sialic acid levels in these patients was also evaluated. In this study, 40 patients with myocardial infarction ranging in age from 42 to 68 years, and 26 healthy volunteers ranging in age from 45 to 71 years were included. Serum total sialic acid determination was carried out by the thiobarbituric acid method of Warren and lipid-bound sialic acfd by the method of Katopodis. Our data shows that a) there is a gradual increase in the levels of serum total sialic acid and lipid-bound sialic acid during the first three days after the acute myocardial infarction and b) the elevation in serum total sialic acid levels correlates with the elevation in lactate dehydrogenase activity only on day 1 following infarction. Therefore, either the shedding or secreting of sialic acid from the cell or cell membrane surface may be partly responsible for an increased serum sialic acid concentration especially on day 1 following myocardial infarction. PMID- 11205690 TI - Concentration of leukocyte elastase in plasma and polymorphonuclear neutrophil extracts in type 2 diabetes. AB - The concentration of leukocyte elastase/alpha1-proteinase inhibitor complexes in plasma and polymorphonuclear neutrophil extracts, and plasma trypsin inhibitory capacity were determined in 88 patients with type 2 diabetes and 47 control subjects. Higher values of these variables were found in patients as compared to controls (p < 0.001). The concentration of elastase was higher in obese patients than in lean ones (p < 0.05 for plasma, p < 0.01 for polymorphonuclear leukocytes). Only leukocyte elastase levels were significantly higher in the group with both micro- and macroangiopathy in comparison to the group with microangiopathy (p < 0.01) or macroangiopathy (p < 0.05) alone. Poor short-term glycaemic control was associated with higher elastase concentration in plasma and neutrophils (p < 0.05). The present study demonstrates that measurements of plasma polymorphonuclear neutrophil elastase level can be considered as a marker of development of diabetic angiopathy. PMID- 11205691 TI - Hypertriglyceridemia characterized by low-density lipoprotein phenotype and lipoprotein lipase gene mutation. AB - A high serum triglyceride (TG) concentration is associated with an increased serum concentration of small, dense low-density lipoprotein (LDL). To further characterize the hypertriglyceridemic condition, we examined sera from 240 subjects for small, dense LDL using non-denaturing polyacrylamide gradient gel electrophoresis. We focused on determining the frequency of the pattern B, which is characterized by a higher proportion of small, dense LDL, among hypertriglyceridemic individuals. The subjects were divided into four groups: a control group (TG < or = 1.65 mmol/l, high-density lipoprotein cholesterol (HDL C) > or =1.17 mmol/l; n = 71), a high TG group (TG > 1.65 mmol/l, HDL-C > or = 1.17 mmol/l; n = 36), a group with high TG and low HDL-C (TG > 1.65 mmol/l, HDL-C < or = 0.91 mmol/l; n = 106), and a low HDL-C group (TG < or = 1.65 mmol/l, HDL-C < or = 0.91 mmol/l; n = 27). We found that pattern B occurs at a high frequency mainly in individuals with high TG and low HDL-C levels. We also observed an increased percentage of LDL within the 20.0 nm to 25.5 nm particle diameter range in this group. Analysis of the lipoprotein lipase gene in this group showed that some mutations seem to be associated with small, dense LDL, resulting in LDL pattern B. PMID- 11205692 TI - Different stability of free and complexed prostate-specific antigen in serum in relation to specimen handling and storage conditions. AB - The effect of sample collection, storage conditions (time and temperature), and freeze-thaw cycles on the stability of free prostate-specific antigen (fPSA), PSA complexed with alpha1-antichymotrypsin (ACT-PSA), and total PSA (tPSA) in serum was studied. The analytes were quantified using immunoassays for tPSA and fPSA on the Elecsys system 2010 and a research assay for ACT-PSA on the ES system (Roche Diagnostics). The stability of the analytes was calculated as percentages of the values measured in samples 1 h after blood collection. When the samples were stored at 37 degrees C, at room temperature or at 4 degrees C, the stability of ACT-PSA was less impaired than that of fPSA. To avoid erroneous results in the determination of PSA isoforms and their corresponding ratios, serum samples should be preserved at 4 degrees C when the analysis is performed within 8 h after blood collection, or they should be stored at -80 degrees C if the analysis is not feasible during that period. PMID- 11205693 TI - Erythrocyte superoxide dismutase and glutathione peroxidase activities, and malondialdehyde and reduced glutathione levels in schizophrenic patients. AB - There is abundant evidence that free radicals are involved in membrane pathology in the central nervous system and that they may play a role in neuropsychiatric disorders, including schizophrenia. In this study, we investigated erythrocyte superoxide dismutase and glutathione peroxidase activities as antioxidant enzymes, malondialdehydes as a sign of lipid peroxidation, and reduced glutathione levels in schizophrenic patients. Activities of superoxide dismutase and levels of malondialdehyde in erythrocytes were greater in all patients (n=48) and in patients with acute (n=16) and chronic schizophrenia (n=32) (p<0.001 for all patients and chronic patient group; p<0.05 for acute patient group). The activities of glutathione peroxidase were lower in patients (p<0.05 for all patients and acute patient group; p=0.051 for chronic patient group) compared with the control group. Mean erythrocyte reduced glutathione was lower in patients than in controls (p<0.05). In the patient group, erythrocyte superoxide dismutase activity was positively correlated with scales and duration of disease and erythrocyte malondialdehyde concentration. These data reveal that antioxidative defense mechanisms might be impaired in schizophrenic patients. PMID- 11205694 TI - Reference change value for HbA1c in patients with type 2 diabetes mellitus. AB - We estimated reference change value and steady state disease biological variation of glycohemoglobin (HbA1c) from serial measurements in 47 clinically stable type 2 diabetes patients whose home-measured capillary glucose was stable throughout the study. Whole blood HbA1c assays were performed by turbidimetric inhibition immunoassay. The analytical imprecision (coefficient of variation) was 7.1% and 5.0% for control materials with HbA1c of 5.1% and 10.7%, respectively (n=152). The sampling interval was 6 months. Patients were classified into three groups (good, acceptable and poor control) according to the American Diabetes Association (ADA) clinical practice recommendations of 1999 based on HbA1c reference interval. Steady state disease biological variation for each control group was 7.9%, 5.4% and 3.9%. HbA1c absolute reference change value was 1.42, 1.50 and 1.37%, or as relative reference change value, 29.1%, 24.4% and 17.8%, respectively. The analytical goal, defined as one-half of the biological variation, was lower than 3.9% for well-controlled patients. PMID- 11205695 TI - Specific oxidase activity of cord serum ceruloplasmin in the newborn. AB - In a study of 50 full-term newborns, we found serum levels of ceruloplasmin, its oxidase activity and specific oxidase activity (activity per unit mass of enzyme protein) which were significantly lower than in adult subjects (p<0.001). A significant correlation was obtained between the specific oxidase activity of the neonatal ceruloplasmin and the transferrin/alpha-fetoprotein ratio (p<0.01), which reflects the maturity of the fetal hepatocyte through its ability to synthesise fetal- and non-fetal-associated proteins. The lower specific oxidase activity of the ceruloplasmin in newborns would be due to a higher relative proportion of apoprotein, and/or other molecular forms with a poor copper content in the oxidase sites. This could be due to an inability to transfer copper into a common intracellular pool for holoceruloplasmin synthesis and biliary copper excretion. A high interindividual variability was found for the specific oxidase activity of the neonatal ceruloplasmin, and in the newborns with higher levels of ceruloplasmin this, from a catalytic point of view, is more similar to the adult form. PMID- 11205696 TI - Sequential evaluation of serum urate concentrations in AIDS patients with infections of the central nervous system. AB - To evaluate the serum urate levels in AIDS patients with infections of the central nervous system (CNS), 46 patients who had at least two measurements of urate were included. A maximum of four measurements per patient were considered: prior to the CNS involvement (U-PRIOR), at the time of CNS involvement (U-CNS), after treatment for the CNS infection (U-AFTER), and the last measurement before death (U-LAST). Serum U-CNS levels were significantly lower than U-PRIOR values (p=0.038). U-AFTER levels were higher than U-CNS in the patients who improved (p=0.25), and lower in the patients who did not improve (p=0.026). There were no significant differences among the four diagnostic groups in U-CNS measurement (p=0.29) but they were found in U-AFTER determinations (p=0.018), probably as a result of the different response to treatment. Hypouricemia seemed to be associated with lower survival periods. We conclude that hypouricemia is common in AIDS patients with CNS infections, probably as a result of increased renal losses of urate, and that it may have prognostic significance. CNS infections are associated with significant decreases in serum urate levels in comparison with previous values. The urate concentrations seem to increase after successful treatment of the CNS infections, whereas they decrease further in patients who do not improve. PMID- 11205697 TI - Evaluation of iron status in anemic patients with rheumatoid arthritis using an automated immunoturbidimetric assay for transferrin receptor. AB - We have evaluated a newly introduced immunoturbidimetric transferrin receptor assay (IdeA TfR-IT, Orion Diagnostica, Finland) in healthy subjects and in a study population consisting of patients with rheumatoid arthritis and juvenile chronic arthritis. The IdeA TfR-IT assay was found to provide reproducible results which were in good agreement with the ELISA assays from Orion Diagnostica (IDeA-ELISA, correlation R2=0.8, n=102) and R&D systems (Quantikine TfR ELISA assay, correlation R2=0.95, n=39). The analysis of the patient samples suggested that, on the basis of serum transferrin receptor and ferritin concentrations, in approximately one third of patients with rheumatoid arthritis anemia is due to the depletion of iron stores. Apparently, in all patients with rheumatoid arthritis iron deficiency must be considered as a potential cause of the anemia. Now, that assays which are suitable for automated analyzers have become available for the measurement of serum transferrin receptor, this analyte has the potential to become a part of the routine evaluation of iron status. PMID- 11205698 TI - IFCC recommended reference method for the determination of the substance concentration of ionized calcium in undiluted serum, plasma or whole blood. AB - A reference method is described for the determination of the substance concentration of ionized calcium in plasma by which ionized calcium (free or unbound) may be reliably determined on the basis of calibration with aqueous solutions with known concentration of ionized calcium. The composition of the calibration solutions is chosen such that the activity coefficient of the calcium ion is assumed to be identical both in the calibration solutions and in "normal" plasma, i.e. by convention, the ionic strength (Im) is 0.160 mol/kg. The convention is adopted of reporting ionized calcium measurements as concentration expressed as mmol/l. The proposed reference method for ionized calcium measurement in plasma is based on the use of a cell consisting of an external reference electrode with a saturated potassium chloride liquid/liquid junction in combination with a calcium ion-selective membrane electrode of defined construction and performance. Procedures for using the reference cell and a protocol for sample measurement are described. The preparation of the calibration solutions to be used are described in detail in Appendix A, secondary calibration solutions and check standards in Appendix B, and reference cell vessel design in Appendix C. PMID- 11205699 TI - Current situation of clinical chemistry in mainland China. PMID- 11205700 TI - Caesarean section on demand--an ethical dilemma. PMID- 11205701 TI - For and against a European quality control of training. AB - In a world of medicine that evolves more and more rapidly, sufficient quality of education in the arts and crafts of our discipline and control of this quality are essential for the progress and vitality of Ob/Gyn. There are variations in training within European countries but with the aim of harmonization in training programmes and the flexibility of quality control mechanisms we will meet our objective that is the high standards in the care of woman throughout Europe. PMID- 11205702 TI - Clinical value of dilatation and curettage for abnormal uterine bleeding. AB - Dilatation and curettage was performed under anesthesia in outpatients in 1,837 patients aged over 26 with a history of abnormal uterine bleeding not associated with pregnancy or ovulation. Fifty-one (2.8%) patients were found to have malignant disease. Of these, 47 patients had endometrial carcinoma. An additional 111 (6.0%) patients were found to have endometrial hyperplasia. The incidence of either malignant disease or endometrial hyperplasia was 9.7% in patients over the age of 40. Complications of this method were noted in 12 (0.7%) patients; only three patients needed to stay in hospital. PMID- 11205703 TI - Evaluation of MUC1 and EGP40 in bone marrow and peripheral blood as a marker for occult breast cancer. AB - Mucin1 (MUCI) is a class of high molecular weight glycoproteins found in the cell membranes of human epithelial cells. Epithelial glycoprotein 40 (EGP40) is a homophilic cell-cell adhesion molecule and expressed on the surface of most simple epithelial cells and the majority of carcinomas. We analyzed the expression of MUC1 and EGP40 in human bone marrow (BM) and peripheral blood (PB) by reverse transcriptase polymerase chain reaction (RT-PCR) and immunocytochemistry (ICC). Eight BM and 95 PB samples from healthy donors, 39 BM and 17 PB samples from patients with haematological malignancies and 45 BM samples from patients with breast cancer were analyzed. MUC1 mRNA and EGP40 mRNA and protein were detected in BM samples and PB samples from healthy donors and from patients with multiple myeloma (MM), non-Hodgkin's lymphoma (NHL) and chronic myelogenous leukaemia (CML). The positive cells showed erythroblast-like and plasmacell-like morphology by immunocytochemistry. The MUC1 and EGP40 nested PCR were positive in 83.3% (10/12) and in 100% (33/33) respectively of BM from patiens with breast cancer who had no evidence of distant metastases. It is concluded that MUC1 and EGP40 is expressed in haematopoietic tissues and haematological malignancies. Therefore, MUC1 and EGP40 expression as a marker for detection of breast cancer cells and micrometastatic epithelial cells in BM and PB is not specific using RT-PCR technique and immunocytochemistry. PMID- 11205704 TI - The renin-aldosterone system during normal and hypertensive pregnancy. AB - Gestational hypertension complicates approximately 5%-7% of pregnancies and it may be deleterious to both maternal and fetal health. Gestational hypertension is a multisystem disorder which always resolves itself after delivery; its primary pathology still remains incompletely clarified. The renin-aldosterone system is a major determinant of sodium balance in pregnancy. To evaluate the changes in renin and aldosterone levels during normal and hypertensive pregnancy we undertook this study. Plasma renin activity and aldosterone levels were measured in 71 pregnant (43 normotensive, 28 hypertensive) and 24 non-pregnant (12 normotensive, 12 hypertensive) women, aged 19-43 years (mean +/- SD 28 +/- 2.8). Women were allocated into the following five groups: Groups 1 and 2 consisted of 12 normotensive and 12 hypertensive non-pregnant women, respectively; group 3 consisted of 20 women (14 normotensive and 6 hypertensive) at 11-19 weeks of gestation; group 4 consisted of 24 women (14 normotensive and 10 hypertensive) at 20-29 weeks of gestation, and group 5 consisted of 27 women (15 normotensive and 12 hypertensive) at 30-37 weeks of gestation. Both plasma renin activity and aldosterone levels progressively increased during normotensive pregnancy and were higher compared to normotensive non-pregnant women. Among hypertensive pregnant women, plasma renin activity levels remained unchanged during the three trimesters of pregnancy and were higher compared to hypertensive non-pregnant women. Only during the third trimester did aldosterone levels significantly increase in hypertensive pregnant women, compared to hypertensive non-pregnant women. Despite stable renin levels, aldosterone levels increased significantly during the third trimester of hypertensive pregnancy. Thus, we conclude that aldosterone biology seems to be directly or indirectly involved in the etiology of gestational hypertension independently of renin levels. PMID- 11205705 TI - Cross-linked type I collagen C- and N-telopeptides in women with bone metastases from breast cancer. AB - This study documents values of biochemical markers of bone remodeling in 106 patients with breast cancer. Based on scintigraphic and radiological findings, patients were divided into 3 groups: 19 patients with bone metastases, 65 patients without bone metastases and normal bone scintigrams, and 22 patients with pathological, non-malignant findings on scintigraphy without proof of bone metastases. Urinary cross-linked type I collagen N-telopeptides (NTx) and serum cross-linked type I collagen C-telopeptides (ICTP) were assessed as markers of bone resorption. Bone alkaline phosphatase (BAP) was assessed as a marker of bone formation. All three markers were significantly higher in patients with bone metastases compared to both patients without skeletal recurrence and those with pathological, non-malignant scintigraphic findings (p < 0.01). There were no statistically significant differences between the latter two groups. The clinical sensitivity for diagnosing bone metastases was 44% for NTx, 65% for ICTP, and 26% for BAP, respectively. The clinical specificitiy for discriminating patients with bone disease from those without were 79%, 91%, and 92% for NTx, ICTP, and BAP, respectively. In conclusion, markers of bone remodeling are increased in patients with breast cancer metastatic to the skeleton. The sensitivity of the markers presented in this paper did not seem to be sufficient enough for early identification of patients with subclinical bone recurrence in a clinical practice setting. PMID- 11205707 TI - Obstetric outcome in grand multipara in the United Arab Emirates. A case control study. AB - OBJECTIVE: To compare the obstetric outcome in grand multiparous and low parous United Arab Emirates women. METHOD: The records of 418 grand multiparous women (study group), defined as having had given birth at least 5 times after completed 22 weeks gestational age, and 418 women of parity 2-4 (control group) were reviewed. RESULTS: Mean parity in the study group was 7.9 +/- 2.4. The number of subjects who attended for antenatal care and the number of visits were equal in both groups. Diabetes mellitus (both overt and gestational) was significantly more common in the study group (p < 0.0001) but there was no significant increase in the incidence of other obstetric complications nor in perinatal mortality rate. Babies of grand multiparous mothers required significantly more admissions to special care unit because of maternal diabetes mellitus (p < 0.0002). CONCLUSION: Diabetes mellitus was more common in grand multiparous United Arab Emirates women but the incidence of other obstetric complications was similar to lower parity women. PMID- 11205706 TI - Relationship between the sonographic pattern of intrauterine growth restriction and acid-base status at the time of cordocentensis. AB - OBJECTIVE: To determine whether there is a difference in acid-base status at the time of cordocentesis between fetuses with symmetric and asymmetric intrauterine growth restriction (IUGR). STUDY DESIGN: Non-anomalous singleton fetuses with IUGR who underwent fetal blood sampling for rapid karyotype analysis from 1992 1995 were retrospectively identified. Cases with gestational age <24 weeks, abnormal karyotype, or evidence of congenital infection were excluded. Fetuses were divided into two groups based on Head Circumference/ Abdominal Circumference Ratio (HC/AC). The asymmetric-IUGR group had HC/AC > or = 95% tile for GA, and the symmetric-IUGR group had HC/AC <95% tile. GA adjusted values of umbilical venous pH, pCO2, pO2, HCO3, hemoglobin and reticulocyte count were calculated by subtracting the mean values for GA from the observed and compared between groups. RESULTS: Both symmetric-IUGR (n = 7) and asymmetric-IUGR (n = 9) had umbilical venous pH and pO2, levels lower than GA normative values. However, there were no differences between groups for any of the parameters studied. CONCLUSIONS: Fetuses with symmetric and asymmetric IUGR due to UPI display a similar degree of acid-base impairment. PMID- 11205708 TI - Anxiety and depression before and after the menopause. AB - OBJECTIVE: Our purpose was to investigate the anxiety and depression at postmenopausal women. METHODS: We studied 32 postmenopausal and 32 premenopausal patients aged between 40-55 years in Kinrikkale University Medical Faculty Obstetric and Gynecology Department. We performed Beck depression scale and State Trait Anxiety Inventory (STAI) I and II on those patients. Blood samples were taken from each patient. We used student's t test, pearson correlation analysis. RESULTS: Beck depression test results were 21.3 +/- 6.7 and 15.1 +/- 5.6 in postmenopausal and premenopausal women respectively (p < 0.001). STAI-I were 50.4 +/- 9.1 and 47.5 +/- 8.5 in this 2 groups (p = 0.19) and STAI-II values were 47.5 +/- 9.1 and 45.4 +/- 7.5 (p = 0.33). We could not find a correlation between anxiety-depression and blood FSH, LH and E2 levels. We found a correlation between parity and depression (r = 0.423 p = 0.01). There were positive correlations between anxiety and depression tests (r = 0.489 p = 0.01 for STAI-I and r = 0.398 p) = 0.01 for STAI-II). CONCLUSION: Depression rate is significantly higher in menopausal women. PMID- 11205709 TI - Study of somatosensory evoked potentials (SSEPs) by stimulating vagina before and after hysterectomy. AB - OBJECTIVE: To assess the changing status of women after hysterectomy using the electrodiagnostic method. STUDY DESIGN: We compared pre- and postoperative somatosensory evoked potentials (SSEPs) through vaginal stimulation in twenty patients undergoing hysterectomy. RESULTS: 1) The latencies (Mean +/- SD) of the first positive peak (P1) and first negative peak (N1) in preoperative vaginal SSEP were 32.89 +/- 3.02 ms and 40.41 +/- 3.43 ms in the left side, 33.25 +/- 4.28 ms and 41.39 +/- 5.46 ms in the right side respectively. 2) The postoperative P1 and N1 latencies were 33.68 +/- 4.50 ms and 42.00 +/- 4.30 ms in the left side, 33.78 +/- 3.10 ms and 42.00 +/- 3.62 in the right side respectively. CONCLUSION: There were no significant differences between the pre- and the postoperative vaginal SSEP by stimulating vagina in patients of hysterectomy. PMID- 11205710 TI - Sertoli-Leydig cell tumor. AB - Sertoli-Leydig cell tumors belong to the group of sex-cord stromal tumors of the ovary. They account for less than 0,5% of all ovarian neoplasms. The majority of these tumors are benign, and almost all are localised unilaterally. Herewith, we describe an ovarian Sertoli-Leydig cell tumor in an 11-year-old girl. Serum levels of estradiol and progesterone were mildly elevated. while testosterone and androstendion levels were raised to around three- and sevenfold upper normal limit respectively on presentation. A left salpingo-oophorectomy was performed. Microscopically, the tumor was intermediately differentiated. At 6 months follow up, there was neither clinical nor sonographical evidence of recurrence, and almost all sex hormone levels had returned to within normal range. Treatment of this pathological entity has to be individualized according to patient age, stage of tumor and degree of differentiation. PMID- 11205711 TI - Intracardiac leiomyomatosis. Case report and literature review. AB - We describe a case of intracardiac leiomyomatosis originating from the uterus, growing up in the inferior vena cava, and extending into the right ventricle. She also found to have lung metastasis. As she declined for further operative intervention, Tamoxifen was given for the control of disease. This case represented an unusual rapid recurrence of intravenous leiomyomatosis which was potentially preventable. To investigate for the appropriate management, a review of the literature concerning this rare condition was made. PMID- 11205712 TI - Percutaneous embolization in the management of intractable vaginal bleeding. AB - AIM: To assess the effectiveness of arterial embolization in gynecological malignancies by Polyvinyl Alcohol particles. MATERIAL AND METHODS: Six patients, four with cervix carcinoma, one endometrium carcinoma, and one vaginal metastasis of ovarian carcinoma underwent percutaneous embolization due to intractable vaginal bleeding. As an embolic agent PVA particles were used. RESULTS: Cessation of the bleeding was observed immediately after the embolization. Complete embolization has been achieved in all the patients Recurrent bleeding did not occur in any of the cases. There were no complications related to the embolization procedure. CONCLUSION: Transarterial embolization is a lifesaving procedure in treating intractable vaginal bleeding. PVA particles are effective and it is a simple way in ceasing the hemorrhage due to pelvic malignancies. PMID- 11205713 TI - Missed abortion complicated by Candida infection in a woman with rested IUD. AB - Although Candida species are frequent saprophytes of the female genital tract, chorioamnionitis or intrauterine fetal infections are rarely caused by these fungi. The present report describes a 34-year-old woman G2, P2, presenting with vaginal bleeding in the 11.6 weeks of gestation. Clinical and sonographic examination revealed a missed abortion and rested IUD. Histopathologically, a fungal chorioamnionitis due to Candida spp. was found at the curetting material, confirmed by detection of C. albicans infection on mycological culture. Foreign intrauterine bodies, like IUD's and cerclage sutures predispose to fungal chorioamnitis or fetal infections. This conditions urge repetetive search for Candida spp. to establish early anti-fungal therapy which may be therapeutic for this hithero rare intrauterine infection. PMID- 11205714 TI - Ritodrine-induced skin rash. AB - A 32-year-old nulligravida was hospitalized because of preterm labor and treated with intravenous ritodrine hydrochloride. After 33 days of therapy, the patient developed a fine maculopapular rash. PMID- 11205715 TI - Etiology of stroke in children. AB - Although the risk factors for stroke in children are numerous and differ greatly from the causes of stroke in adults, a thorough diagnostic evaluation can identify one or more risk factors in most patients. Cardiac disorders and hemoglobinopathy are the most common causes of ischemic infarction, whereas various congenital anomalies of the blood vessels or defects in coagulation or platelet function are often found in children with intraparenchymal hemorrhage. More than one risk factor is commonly identified, especially in children with dural venous thrombosis. Identification of the underlying risk factors for cerebrovascular disorders in children is important because many of the risk factors can be treated, reducing the risk of subsequent strokes. PMID- 11205716 TI - New radiographic techniques to evaluate cerebrovascular disorders in children. AB - The radiographic evaluation of the pediatric patient with cerebrovascular disease has dramatically improved during the past decade. Few new technologies have been introduced, but significant new developments in data acquisition and post processing have resulted from refinements in both software and, to a lesser extent, hardware. This review focuses on the advantages and limitations of the different imaging modalities and their recommended role in managing the pediatric patient who presents with signs or symptoms of cerebrovascular disease. PMID- 11205717 TI - Neonatal cerebral infarction. AB - Neonatal cerebral infarction in term infants has many possible causes, including bacterial meningitis, inherited or acquired coagulopathies, trauma, and hypoxia ischemia. However, a specific cause often cannot be identified. Neurologic symptoms in the neonatal period are often subtle and nonspecific, even in infants with large infarctions involving an entire cerebral artery distribution. The most common presenting symptom is focal motor seizures of the contralateral limbs. Cranial magnetic resonance imaging, especially with diffusion-weighting, is the most sensitive imaging modality, although ultrasonography with Doppler imaging of cerebral blood flow is useful in the neonate who is too ill to transport. Neurodevelopmental outcome is often surprisingly good, with many infants making a complete recovery of motor function. The effect of neonatal stroke on cognitive function, especially language acquisition and emotional and social development, has not been fully established. PMID- 11205718 TI - Cerebrovascular arterial dissection in children and young adults. AB - Dissection of the cervical and intracranial portions of the carotid and vertebrobasilar arteries may occur spontaneously or in association with trauma or other underlying risk factors. Astute recognition allows appropriate diagnostic and therapeutic protocols to be instituted. Dissection of extracranial carotid and vertebral arteries differ from their intracranial counterparts, both in terms of presentation and prognosis. Limited data are available regarding the most effective medical treatment of dissection in children and young adults. Interventional neuroradiology may offer a new approach in difficult cases. A multicenter controlled clinical trial is needed to assess the most effective treatment. PMID- 11205719 TI - Prothrombotic disorders and ischemic stroke in children. AB - Childhood ischemic stroke, including arterial ischemic stroke (AIS) and sinovenous thrombosis (SVT), is relatively rare in children but can result in devastating morbidity and mortality. An understanding of the etiology of childhood stroke is important because strategies for primary and secondary prevention can be devised. Prothrombotic disorders may contribute to the etiology of childhood stroke, and include deficiencies of antithrombin, protein C, protein S, plasminogen, and presence of Factor V Leiden, Prothrombin gene G20210A, dysfibrinogenemia, antiphospholipid antibodies, hyperhomocysteinemia, and elevated lipoprotein (a). The overall incidence of prothrombotic disorders in childhood AIS is estimated to be 20% to 50% in most studies and, in childhood SVT, to be 33% to 99%. In addition, hyperlipidemia, polycythemia, iron deficiency anemia, and platelet disorders may result in a prothrombotic state associated with ischemic stroke. The etiologic contribution of these prothrombotic disorders to initial and recurrent stroke has not been clearly defined; however, additional risk factors are usually present in affected children. Given the prevalence of prothrombotic disorders in childhood stroke, and their likely causative role, children with stroke should be screened for prothrombotic disorders. Future prospective and multicenter studies will elucidate the contribution of specific prothrombotic disorders to initial and recurrent stroke, and optimal therapy. PMID- 11205720 TI - Stroke in children: recognition, treatment, and future directions. AB - Childhood stoke is increasingly recognized, but studies remain largely descriptive. Important differences from adult stroke include the following: (1) frequently delayed or missed diagnosis, (2) heterogenous and overlapping risk factors, and (3) developmental differences in the cerebrovascular, neurologic, and coagulation systems. These aspects limit the extrapolation of the results of adult stroke research and present challenges in caring for children with stroke. The incidence of childhood ischemic stroke exceeds 3.3 in 100,000 children per year, more than double the estimates from past decades. The increased incidence reflects, in part, increased survival in previously fatal conditions predisposing to stroke, including congenital heart disease, sickle cell anemia, and leukemia. Risk factors for stroke are recognized in more than 75% of children. Common risk factors include congenital heart disease and sickle cell disease. Progressive arteriopathies, including vasculitis and moyamoya syndrome, are rare in children with stroke; however, transient arteriopathies including post-varicella angiopathy are increasingly recognized. Prothrombotic abnormalities are frequently present but of unclear significance. Adverse outcomes after childhood stroke, including death in 10%, recurrence in 20%, and neurologic deficits in two thirds of survivors could be reduced with available stroke treatments. Aggressive prehospital emergency care and transfer could improve access to hyperacute stroke therapies including tPA. Currently, the diagnosis is delayed by more than 24 hours from onset in most children. As in adults, tPA will likely produce unacceptable rates of intracerebral hemmorrhage unless given within 3 hours of stroke symptom onset. The appropriate choices for in hospital treatment and secondary preventative strategies, including aspirin and anticoagulants, are controversial. Empiric recommendations are published; however, age-appropriate clinical trials are urgently needed. The large multinational networks of investigators necessary for designing and conducting these future trials are now being formed. PMID- 11205721 TI - Diastolic heart failure: diagnosis and treatment. AB - The most frequent hospital diagnosis-related group is congestive heart failure (CHF). CHF increases dramatically with age, making it an important problem in our aging population. CHF is caused by a primary abnormality in diastolic function (diastolic heart failure [DHF]) in 50% of patients with CHF who are > 70 years of age. Mortality rates in patients with DHF are comparable to those of patients with systolic heart failure, approaching 50% over 5 years. Successful therapy of DHF requires making a correct diagnosis, identifying the underlying cause, and applying specific and individualized treatment. PMID- 11205722 TI - Management of advanced heart failure. AB - Congestive heart failure (CHF) due to progressive systolic dysfunction has become a modern-day epidemic. Despite the increased incidence and prevalence, significant progress has been made in the past 10 to 15 years in the treatment of CHF at all stages. The current outlook for patients with newly diagnosed, mild heart failure is encouraging. It should be noted, however, that most of the morbidity and health care expenditure is incurred by a minority of patients diagnosed with CHF who are in the advanced stages of their disease. The thrust of this article will be to provide practical advice beyond current guidelines on the management of advanced CHF. PMID- 11205723 TI - Upcoming therapies for heart failure. AB - Treatment of maladaptive neurohormonal activation in congestive heart failure (CHF) has been successful because basic cardiovascular science findings have been confirmed or dismissed through the use of well-controlled, large-scale clinical trials. It should be no surprise that this exciting approach is evolving toward novel agents and devices directed toward other pathways involved in CHF neurohormonal/cytokine activation. Several of these are in advanced clinical development and are likely to play prominent roles in CHF therapy in the near future. PMID- 11205724 TI - Surgical options for the treatment of heart failure. AB - This article will examine the role of specific surgical interventions for congestive heart failure (CHF). The most definitive surgical option for severe end-stage heart failure is cardiac transplantation. In general, patients considered for heart transplant should have severe heart disease despite all other therapies with a high risk of death within 1 year. Noncardiac conditions that would by themselves shorten life expectancy or increase the risks of rejection, infection, or other fatal complication, should not be present. However, in light of the limited donor pool, complications associated with long term immunosuppressive therapy, and the ever-increasing number of CHF patients, the role of cardiac transplantation for CHF will continue to be limited. The conduct of and evaluation for cardiac transplantation has been well described previously and therefore will not be evaluated in this review (1); however, there has been recent progress in the genetic modification of animal organs for potential use in transplantation (xenografts) (2). If these developments come to fruition, then cardiac transplantation/organ replacement may become a surgical option for a much greater number of CHF patients. One alternative approach to complete cardiac transplantation is the surgical placement of transformed cells into the diseased myocardium, briefly discussed under "Future Directions." This article will examine surgical options that are currently being used for CHF patients, surgical modalities that are currently under clinical evaluation, and finally, potential future therapies with respect to surgical options for heart failure. PMID- 11205725 TI - Optimizing the science of drug development: opportunities for better candidate selection and accelerated evaluation in humans. PMID- 11205727 TI - Synergistic effect of enhancers for transdermal drug delivery. AB - Transdermal drug delivery offers a non-invasive route of drug administration, although its applications are limited by low skin permeability. Various enhancers including iontophoresis, chemicals, ultrasound, and electroporation have been shown to enhance transdermal drug transport. Although all these methods have been individually shown to enhance transdermal drug transport, their combinations have often been found to enhance transdermal transport more effectively than each of them alone. This paper summarizes literature studies on these combinations with respect to their efficacy and mechanisms. PMID- 11205726 TI - Protein kinases as therapeutic targets. AB - Protein kinases and phosphatases are likely targets for the development of therapeutic drugs since they are involved in specific signaling pathways which regulate cell functions such as metabolism, cell cycle progression, cell adhesion, vascular function and angiogenesis. Protein phosphorylation and dephosphorylation serve as molecular switches for modulating these processes and the level and duration of each is a highly regulated process in normal cells. Several compounds that inhibit the activity of tyrosine kinases are being evaluated as cancer therapeutic agents in clinical trials. Diabetes and complications of diabetes also involve deregulated levels of protein kinases. New approaches for regulating kinase gene expression include specific antisense oligonucleotides for inhibiting post-transcriptional processing of the messenger RNA, naturally occurring products and their chemical derivatives to inhibit kinase activity, and monoclonal antibodies to inhibit receptor linked kinases. Inhibition of phosphatases also serves to alter the duration of phosphorylation by kinases. Considerations for development of effective inhibitors include non specific actions of compounds, cellular uptake, multiple intracellular targets that can dilute the effective cellular concentration of an agent, and tissue specificity. Kinase inhibitors may allow other therapeutic agents additional time to become effective and they may act synergistically with current treatments. PMID- 11205728 TI - Generation of micro-particles of proteins for aerosol delivery using high pressure modified carbon dioxide. AB - PURPOSE: To investigate the feasibility of using the Aerosol Solvent Extraction System (ASES) to generate microparticles of proteins suitable for aerosol delivery from aqueous-based solutions. METHODS: The ASES technique using high pressure carbon dioxide modified with ethanol was utilised for the generation of microparticles of proteins (lysozyme, albumin, insulin and recombinant human deoxyribonuclease (rhDNase)) from aqueous solutions. Particle size, morphology, size distributions and powder aerosol performance were examined. The biochemical integrity of the processed proteins was assessed by testing the level of molecular aggregation using size exclusion chromatography and by bioassay technique for lysozyme. RESULTS: Proteins were precipitated as spherical particles ranging in size from 100 to 500 nm. The primary nano-sized particles agglomerated to form micron-sized particles during the precipitation process. The median size of the particles was a function of the operating conditions. In-vitro aerosol performance tests showed that the percent fine particle mass (< 5 microm) was approximately 65%, 40% and 20% for lysozyme, albumin and insulin, respectively. Negligible loss in the monomer content or biological activity was observed for lysozyme. Insulin exhibited slight aggregation and 93% of the monomer was retained after processing. Albumin was affected by processing and only 50-75% of the monomer was retained compared with 86% in the original material. However, rhDNase was substantially denatured during processing as shown by the significantly reduced monomer content. CONCLUSIONS: Micron-sized particles of lysozyme, albumin and insulin with satisfactory inhalation performance were successfully generated from aqueous solutions using the modified ASES technique. The biochemical integrity of the processed proteins was a function of the operating conditions and the nature of the individual protein. PMID- 11205729 TI - Formation and isolation of spherical fine protein microparticles through lyophilization of protein-poly(ethylene glycol) aqueous mixture. AB - PURPOSE: Preparation of spherical fine protein microparticles by the lyophilization of a protein-poly(ethylene glycol) (PEG) aqueous mixture was investigated. The main objective was to establish a method for preparing protein microparticles suitable for pharmaceutical production. METHODS: Aqueous solutions containing bovine serum albumin (BSA) and PEG at various mixing ratios were freeze-dried. The lyophilizates were dispersed in methylene chloride and subjected to particle size analysis. Analogous studies were performed using several model proteins. A phase diagram of the PEG-BSA aqueous system was obtained by the titration method. RESULTS: The particle size of BSA decreased as the PEG-BSA ratio increased. A bending point was observed in this relationship, at which the PEG-BSA ratio coincided with that of the critical point on the phase diagram of the PEG-BSA system. These results were explained by the freezing induced condensation, followed by phase separation in the PEG-BSA system. CONCLUSIONS: Spherical fine protein microparticles were successfully obtained at high yield and without any activity loss under optimum conditions. This new technology could be applicable to proteins with a wide range of molecular weights, and is expected to be developed for dry powder inhalations or long-term sustained release microsphere formulations. PMID- 11205730 TI - Protein spray-freeze drying. Effect of atomization conditions on particle size and stability. AB - PURPOSE: To investigate the effect of atomization conditions on particle size and stability of spray-freeze dried protein. METHODS: Atomization variables were explored for excipient-free (no zinc added) and zinc-complexed bovine serum albumin (BSA). Particle size was measured by laser diffraction light scattering following sonication in organic solvent containing poly(lactide-co-glycolide) (PLG). Powder surface area was determined from the N2 vapor sorption isotherm. Size-exclusion chromatography (SEC) was used to assess decrease in percent protein monomer. Fourier-transform infrared (FTIR) spectroscopy was employed to estimate protein secondary structure. PLG microspheres were made using a non aqueous, cryogenic process and release of spray-freeze dried BSA was assessed in vitro. RESULTS: The most significant atomization parameter affecting particle size was the mass flow ratio (mass of atomization N2 relative to that for liquid feed). Particle size was inversely related to specific surface area and the amount of protein aggregates formed. Zinc-complexation reduced the specific surface area and stabilized the protein against aggregation. FTIR data indicated perturbations in secondary structure upon spray-freeze drying for both excipient free and zinc-complexed protein. CONCLUSIONS: Upon sonication, spray-freeze dried protein powders exhibited friability, or susceptibility towards disintegration. For excipient-free protein, conditions where the mass flow ratio was > -0.3 yielded sub-micron powders with relatively large specific surface areas. Reduced particle size was also linked to a decrease in the percentage of protein monomer upon drying. This effect was ameliorated by zinc-complexation, via a mechanism involving reduction in specific surface area of the powder rather than stabilization of secondary structure. Reduction of protein particle size was beneficial in reducing the initial release (burst) of the protein encapsulated in PLG microspheres. PMID- 11205732 TI - An increased throughput method for the determination of partition coefficients. AB - PURPOSE: To present an increased throughput automated shake-flask method for the direct determination of the partition coefficients of solutes between octan-1-ol and buffer. METHOD: The traditional shake-flask method has been transferred onto 96-well plate technology and a robotic liquid handler has been used for sample preparation. A custom programmed Gilson autosampler samples the organic and aqueous phases directly from the plate, circumventing the need for any manual separation. Analyses are performed by reverse phase high performance liquid chromatography (RP-HPLC). Generic fast gradient RP-HPLC conditions are used to eliminate chromatographic method development time and reduce analysis time. RESULTS: A full validation of the automated method is presented for a range of compounds with log D values between -2 and 4. CONCLUSIONS: The advantages and limitations of this direct measurement method are discussed. The use of this methodology provides a means to rapidly assess log D values for large compound arrays. PMID- 11205731 TI - Use of artificial neural networks to predict drug dissolution profiles and evaluation of network performance using similarity factor. AB - PURPOSE: To use artificial neural networks for predicting dissolution profiles of matrix-controlled release theophylline pellet preparation, and to evaluate the network performance by comparing the predicted dissolution profiles with those obtained from physical experiments using similarity factor. METHODS: The Multi Layered Perceptron (MLP) neural network was used to predict the dissolution profiles of theophylline pellets containing different ratios of microcrystalline cellulose (MCC) and glyceryl monostearate (GMS). The concepts of leave-one-out as well as a time-point by time-point estimation basis were used to predict the rate of drug release for each matrix ratio. All the data were used for training, except for one set which was selected to compare with the predicted output. The closeness between the predicted and the reference dissolution profiles was investigated using similarity factor (f2). RESULTS: The f2 values were all above 60, indicating that the predicted dissolution profiles were closely similar to the dissolution profiles obtained from physical experiments. CONCLUSION: The MLP network could be used as a model for predicting the dissolution profiles of matrix-controlled release theophylline pellet preparation in product development. PMID- 11205733 TI - Application of high performance liquid chromatography coupled with ultraviolet spectroscopy and electrospray mass spectrometry to the characterisation of ellagitannins from Terminalia macroptera roots. AB - PURPOSE: Terminalia macroptera roots are used in Guinea-Bissau and other West African countries to treat infectious diseases like gonorrhoea. Previous work showed an ethanol extract of T. macroptera roots (T) to have an in vitro antimicrobial profile against Neisseria gonorrhoae (including resistant strains) and enteropathogenic agents. The most active fractions of this extract were identified as the diethyl ether (T2) and water (T5) fractions. The aim of the present study was the identification of major compounds present in T and simultaneously in T2 or T5. METHODS: The T extract and T2 and T5 fractions were analysed by high performance liquid chromatography coupled with ultraviolet photodiode array (LC-UV) spectroscopy and electrospray ionization mass spectrometry (ES-MS). These analyses indicated the presence of ellagitannin derivatives. In order to confirm the identities of the detected compounds, they were isolated from T2 and T5 by preparative chromatographic techniques and identified by spectroscopic methods including tandem mass spectrometry. RESULTS: By using LC-UV-ES-MS, four major compounds (ellagic acid, gallic acid, punicalagin, terchebulin) could be identified in the T extract. Three other compounds (3,3'di-O-methylellagic acid, 3,4,3',4'-tetra-O-methylellagic acid, terflavin A) were also isolated and identified. CONCLUSIONS: LC-UV-ES-MS is a useful technique for the analysis of mixtures containing ellagitannins. PMID- 11205735 TI - In vivo study of the effect of valpromide and valnoctamide in the pilocarpine rat model of focal epilepsy. AB - PURPOSE: We evaluated the effectiveness of the commonly used antiepileptic drug sodium valproate (400 mg/kg) and two of its amide derivatives, valpromide and valnoctamide (both 100 mg/kg), in an in vivo rat model of focal epilepsy. Our main interest was to get insight into possible changes in extracellular amino acid neurotransmitter levels following administration of the drugs, both in control and in epileptic conditions. METHODS: Seizures were evoked in freely moving rats by intrahippocampal administration of pilocarpine via a microdialysis probe (10 mM for 40 min at 2 microl/min). Microdialysis was also used as in vivo sampling technique and alterations in extracellular hippocampal glutamate and GABA levels were monitored. Electrophysiological evidence for the presence or absence of seizures was simultaneously recorded with electrocorticography. RESULTS: The focally evoked pilocarpine-induced seizures were completely prevented by acute intraperitoneal pretreatment with each of the three drugs in the respective doses. Effective protection was reflected in the electrocorticographic recordings and in the lack of sustained elevations of the extracellular glutamate levels after pilocarpine perfusion. Little effects were seen on the basal extracellular amino acid levels after systemic administration of each of the compounds, nor after the intrahippocampal administration of sodium valproate. CONCLUSIONS: Valnoctamide and valpromide (100 mg/kg) proved to be at least as effective as their parent compound sodium valproate (400 mg/kg) against pilocarpine-induced seizures. All three compounds however failed to induce significant initial alterations in extracellular hippocampal GABA release. This questions the enhancement of GABA-mediated inhibition as being one of their mechanisms of action. PMID- 11205734 TI - Dextran-methylprednisolone succinate as a prodrug of methylprednisolone: immunosuppressive effects after in vivo administration to rats. AB - PURPOSE: To study the immunosuppressive activities of a macromolecular prodrug of methylprednisolone (MP), dextran-methylprednisolone succinate (DEX-MPS), in rats. METHODS: Single 5 mg/kg (MP equivalent) doses of MP or DEX-MPS were administered intravenously to rats, and blood and spleen samples were collected over 96 h. The immunosuppressive activity was determined by the effects of the free or dextran conjugated drug on the mitogen-stimulated spleen lymphocyte proliferation. Additionally, the number of lymphocytes in the spleen cell suspensions was estimated. Further, the plasma and spleen concentrations of the conjugated and free MP were determined using size-exclusion and reversed-phase chromatographic methods, respectively. RESULTS: Both MP and DEX-MPS injections resulted in the inhibition of the spleen lymphocyte proliferation. However, the maximal effect of DEX-MPS was significantly (P < 0.003) more intense (approximately 100% inhibition) and delayed (24 h) relative to that of MP (approximately 50% inhibition at 2 h). The DEX-MPS injection also resulted in a significantly (P < 0.0001) higher decline in the estimated number of spleen lymphocytes (approximately 80% at 24 h), compared with the MP injection (approximately 30% at 2 hr). Whereas the plasma and spleen concentrations of MP could not be measured at > or = 2 h after the drug injection, relatively high concentrations of DEX-MPS persisted in plasma and spleen for 24 h and 96 h, respectively. CONCLUSION: Dextran-methylprednisolone conjugate can effectively deliver the corticosteroid to its site of action for immunosuppression, resulting in more intense and sustained effects when compared with the free drug administration. PMID- 11205736 TI - Does epidermal turnover reduce percutaneous penetration? AB - PURPOSE: After its removal from the skin surface, chemical remaining within the skin can become systemically available. The fraction of chemical in the skin that eventually enters the body depends on the relative rates of percutaneous transport and epidermal turnover (i.e., stratum corneum desquamation). Indeed, some investigators have claimed that desquamation is an efficient mechanism for eliminating dermally absorbed chemical from the skin. METHODS: The fate of chemical within the skin following chemical contact was examined using a mathematical model representing turnover of and absorption into the stratum corneum and viable epidermis. The effects of turnover rate, exposure duration, penetrant lipophilicity, and lag time for chemical diffusion were explored. RESULTS: These calculations show that significant amounts of chemical can be removed from skin by desquamation if epidermal turnover is fast relative to chemical diffusion through the stratum corneum. However, except for highly lipophilic and/or high molecular weight (>350 Da) chemicals, the normal epidermal turnover rate is not fast enough and most of the chemical in the skin at the end of an exposure will enter the body. CONCLUSIONS: Epidermal turnover can significantly reduce subsequent chemical absorption into the systemic circulation only for highly lipophilic or high molecular weight chemicals. PMID- 11205737 TI - The in vitro cell association of invasin coated polylactide-co-glycolide nanoparticles. AB - PURPOSE: To determine the effect of particle size and ligand surface density on the cellular association of poly lactide-co-glycolide nanoparticles covalently coated with bacterial invasin. METHODS: Poly lactide-co-glycolide nanoparticles containing a flourescent probe were prepared at four diameters 155 nm, 200 nm, 375 nm and 600 nm using standard techniques. Bacterial invasin was covalently coupled to the particles surface at varying surface concentrations using a water soluble carbodiimide. The modified particle's cellular association with HEp2 2B cells in tissue culture was determined using flow cytometry. RESULTS: Cellular association of modified nanoparticles was time dependent, abolished at low temperature, competitively inhibited by free invasin or the RGD peptide ligand and saturable. Increased cell association was produced by increasing the particle's surface invasin concentration however, this effect was size dependent. Small particles (155 nm and 200 nm) exhibiting a maximal association with increasing invasin concentration whilst the larger particles (375 nm and 600 nm) provide a minimum at low invasin concentrations. CONCLUSIONS: Modified particle cell association provided results commensurate with a receptor dependent uptake mechanism related to the presence of invasin. The size and surface concentration dependency however illustrate that application of these ligands to particulate drug delivery or targeting systems will be controlled by their natural cellular association properties. PMID- 11205738 TI - Absorption and disposition of a selective aldosterone receptor antagonist, eplerenone, in the dog. AB - PURPOSE: The present study was conducted to characterize the pharmacokinetics of eplerenone (EP), a selective aldosterone receptor antagonist, and its open lactone ring form in the dog. METHODS: Pharmacokinetic studies of EP were conducted in dogs following i.v., oral, and rectal dosing (15 mg/kg) and following intragastric, intraduodenal, intrajejunal, and intracolonic dosing (7.5 mg/kg). RESULTS: After oral administration, the systemic availability of EP was 79.2%. Systemic availabilities following administration via other routes were similar to that following oral administration. The half-life and plasma clearance of EP were 2.21 hr and 0.329 l/kg/hr, respectively. Plasma concentrations of the open lactone ring form were lower than EP concentrations regardless of the route of administration. The C-14 AUC in red blood cells was approximately 64% and 68% of the plasma AUC for i.v. and oral doses. Percentages of the dose excreted as total radioactivity in urine and feces were 54.2% and 40.6%, respectively, after i.v. administration, and 40.7% and 52.3%, respectively, after oral administration. The percentages of the dose excreted in urine and feces as EP were 13.7% and 2.5%, respectively, after i.v. administration, and 2.1% and 4.6% after oral administration, respectively. Approximately 11% and 15% of the doses were excreted as the open form following i.v. and oral doses. CONCLUSIONS: EP was rapidly and efficiently absorbed throughout the gastrointestinal tract, resulting in a good systemic availability. The drug did not preferentially accumulate in red blood cells. EP was extensively metabolized; however, first-pass metabolism after oral and rectal administration was minimal. EP and its metabolites appear to be highly excreted in the bile. PMID- 11205740 TI - Physical characterization of large porous particles for inhalation. PMID- 11205739 TI - The role of metabolites in bioequivalency assessment. III. Highly variable drugs with linear kinetics and first-pass effect. AB - PURPOSE: Simulated pharmacokinetic (PK) studies were done to determine the effect of intrinsic clearance (CL(INT)) on the probability of meeting bioequivalence criteria for extent (AUC) and rate (Cmax) of drug absorption when the absorption rate and fraction absorbed (F) were formulated either to be equivalent or to differ by 25%. METHODS: Simulated PK studies were done using a linear first-pass model with CL(INT) values ranging from 15 L/HR to 900 L/HR. Test/Reference absorption rate constants (Ka) and fraction absorbed (Fa) ratios of 1.0 or 1.25 were used for all simulations. The impact of the value of CL(INT) and its intrasubject variation upon the probability of concluding bioequivalence at the two different Ka and F ratios was studied. Additionally, the effect of fraction metabolized i.v., (Fm) on the probabilities of concluding equivalence was studied at values of 0.25 and 0.75. RESULTS: When CL(INT) values were raised above those for liver blood flow, the frequency of trials in which bioequivalence was correctly declared decreased when parent AUC was used as a bioequivalence criterion. Only when CL(INT) exceeded liver blood flow did the metabolite become important in assessing extent of absorption. CONCLUSIONS: The Cmax for the parent drug provided the most accurate assessment of bioequivalence. The Cmax for the metabolite was insensitive to changes related to rate of input, and when CL(INT) exceeded liver blood flow, evaluation of the metabolite Cmax data may lead to a conclusion of bioequivalence for products that were not. PMID- 11205741 TI - Signal transducers and activators of transcription 5B potentiates v-Src-mediated transformation of NIH-3T3 cells. AB - Previously, we reported that whereas both signal transducers and activators of transcription (STAT) 5A and STAT5B can be activated with respect to tyrosine phosphorylation and DNA binding potential by Src kinase, only STAT5B was translocated to the nucleus, where it presumably activates unique downstream responses. To help elucidate the functional consequences of STAT5B activation by v-src, the properties of stably transfected NIH-3T3 cells containing both an intact and a dominant negative, COOH-terminal-truncated isoform of STAT5B were investigated. STAT5B enhanced the transforming potential of v-Src as reflected by both an increase in focus formation and growth in soft agar. STAT5B also enhanced v-Src-induced cell cycle progression and cell motility in NIH-3T3 cells. Furthermore, the dominant negative, COOH-terminal-truncated isoform of STAT5B was able to partially suppress v-Src-mediated cell transformation. These results support the hypothesis that STAT5B may enhance Src/Abl-induced tumorigenesis. Accordingly, the equilibrium between STAT5B and STAT5A and their naturally occurring truncated forms may therefore play a key role in the etiology of certain cancers. PMID- 11205742 TI - Morphologic conversion of a neuroblastoma-derived cell line by E6-mediated p53 degradation. AB - Neuroblastoma-derived tumor cells, unlike cells from other tumor types, characteristically express a wildtype but cytoplasmically sequestered p53 protein. To ascertain whether the p53 in these cells retained any physiological activity, we inactivated it in SK-N-SH cells, a neuroblastoma-derived cell line, by introducing the human papilloma virus type 16 E6 expression plasmid. Parent SK N-SH cell cultures are composed of two cell types exhibiting characteristic morphologies designated neuroblastic (N-type) or substrate-adherent fibroblastic (S-type) cells, both of which have been shown to spontaneously transdifferentiate or interconvert. We report here that down-regulation of p53 resulted in conversion of SK-N-SH cells to the substrate-adherent fibroblast-like S-type cells. The morphologic conversion was accompanied by a loss of neurofilament expression, a marker for the neuronal N-type cells, an increase in the expression of vimentin, and a lack of responsiveness to retinoic acid-induced neuronal differentiation. Importantly, we did not observe N-type cells in the E6 transfected cell population, suggesting that they were incapable of transdifferentiating to the N-type morphology. We also tested the ability of these E6-transfected S-type cells to form colonies in soft agar and observed a markedly reduced capacity of these cells to do so when compared with the parent and mutant E6-transfected cells. These results suggest that p53 is required for the maintenance of the neuroblastic tumorigenic phenotype. PMID- 11205743 TI - Polo-like kinase interacts with proteasomes and regulates their activity. AB - The polo-like kinase (Plk) has been shown to be associated with the anaphase promoting complex at the transition from metaphase to anaphase and to regulate ubiquitination, the process that targets proteins for degradation by proteasomes. In this study, we have identified proteasomal proteins interacting with Plk by mass spectrometry and found that Plk and 20S proteasome subunits could be reversibly immunoprecipitated from both human CA46 cells and HEK 293 cells transfected with HA-Plk. Furthermore, both coprecipitated Plk and baculovirus expressed Plk were able to phosphorylate proteasome subunits, and metabolic labeling studies indicate that Plk is partially responsible for the phosphorylation of 20S proteasome subunits C9 and C8 in vivo. In addition, phosphorylation of proteasomes by Plk enhanced proteolytic activity toward an artificial substrate Suc-L-L-V-Y-AMC in vitro and in vivo. Finally, we were also able to detect Plk associated with 26S proteasomes under certain conditions. Together our results suggest that Plk is an important mitotic regulator of proteasome activity. PMID- 11205744 TI - Differences in early and late responses between neurotrophin-stimulated trkA- and trkC-transfected SH-SY5Y neuroblastoma cells. AB - Despite their sympathetic neuroblast origin, highly malignant neuroblastoma tumors and derived cell lines have no or low expression of the neurotrophin receptor genes, trkA and trkC. Expression of exogenous trkA in neuroblastoma cells restores their ability to differentiate in response to nerve growth factor (NGF). Here we show that stable expression of trkC in SH-SY5Y neuroblastoma cells resulted in morphological and biochemical differentiation upon treatment with neurotrophin-3 (NT-3). To some extent, trkA- and trkC-transfected SH-SY5Y (SH SY5Y/trkA and SH-SY5Y/trkC) cells resembled one another in terms of early signaling events and neuronal marker gene expression, but important differences were observed. Although induced Erk 1/2 and Akt/PKB phosphorylation was stronger in NT-3-stimulated SH-Y5Y/trkC cells, activation of the immediate-early genes tested was more prominent in NGF-treated SH-SY5Y/ trkA cells. In particular, c fos was not induced in the SH-SY5Y/trkC cells. There were also phenotypic differences. The concentrations of norepinephrine, the major sympathetic neurotransmitter, and growth cone-located synaptophysin, a neurosecretory granule protein, were increased in NGF-treated SH-SY5Y/trkA but not in NT-3-treated SH SY5Y/trkC cells. Our data suggest that NT-3/p145trkC and NGF/p140trkA signaling differ in some aspects in neuroblasoma cells, and that this may explain the phenotypic differences seen in the long-term neurotrophin-treated cells. PMID- 11205745 TI - Differentiation of Ly49s-positive or -negative natural killer cells is inhibited by anti-H-2b monoclonal antibodies acting at the level of bone marrow progenitors from B6 mice. AB - To investigate the role of MHC class I on in vitro differentiation of natural killer (NK) cells, a CD44low/-CD2-classlow population was isolated from mouse bone marrow. This population, which lacked expression of NK-1.1, Ly49A, Ly49C/I, and Ly49G, generated populations of NK-1.1+ NK cells expressing Ly49A, Ly49C/I, or Ly49G when cocultured for 13 days with syngeneic supportive stromal cells in the presence of interleukin 2. Ly49A and Ly49C/I were absent on the progeny of progenitors tested after 7 days of culture but were expressed as a late event together with low-level expression of NK-1.1, from day 8 of culture. The addition of anti-H-2b monoclonal antibody to cultures at day 0 inhibited proliferation of progenitors supported by either syngeneic, allogeneic, or H-2b-deficient stromal cells, thus suggesting that the effect was not exerted on stromal cells. Additional analyses demonstrated that class Ilow progenitors generated class I+ cells on which the anti-H-2b monoclonal antibody exerted its inhibitory effect. PMID- 11205747 TI - [The diagnostic value of modelling the urinary bladder wall in women with pelvis minor tumors]. AB - Basing on the authors' own observations and literature data diagnostic value of different imaging techniques was presented in differentiating pathologic changes deduced from deformations of urinary bladder walls. Modelling of the walls has proved to enable the localisation of the tumour without determining its character. The degree of modelling of urinary bladder wall, however, is proportionate to the size of tumour. In a considerable number of cases it was possible to exclude infiltration of the bladder wall or to show overgrowing it by neoplastic mass. PMID- 11205746 TI - Mechanism of induction of transforming growth factor-beta type II receptor gene expression by v-Src in murine myeloid cells. AB - Transforming growth factor (TGF)-beta1 plays an important role during hematopoiesis. Previously, we had shown that the growth of a v-Src-transformed myeloid cell line was markedly more inhibited by TGF-beta treatment when compared with the wild-type myeloid cell line. To investigate the increased growth sensitivity of the v-Src-transformed myeloid cell line, 32D-src, to TGF-beta, we examined expression of the TGF-beta type II receptor (TGF-beta RII) gene in myeloid cell lines. Northem blot analysis showed that expression of approximately 8- and 6-kb species of TGF-beta RII transcripts was markedly increased in the 32D src cell line. The expression of the TGF-beta RII promoter linked to a reporter gene was increased 23-fold by v-Src. DNA transfection and electrophoretic mobility shift assay revealed that v-Src induces TGF-beta RII promoter activity through an AP1/ATF2-like sequence (-219 to -172), ETS binding sites (+1 to +36), and the inverted CCAAT box (-81 to -77). Novel DNA-protein complexes with ETS binding sites are significantly increased in v-src-transformed cell lines compared with the control cell line. These results suggest that v-Src induces activity of the TGF-beta RII promoter through multiple elements by inducing expression of nuclear proteins interacting with these elements. PMID- 11205748 TI - [Historical aspects of dental caries and its treatment]. AB - The study presents the history of scientific research of caries incidence on the basis of the archaeological and excavated remains and other historical sources. The analysis of teeth curing was carried out on historical grounds covering early ancient and medieval methods as well as contemporary ways of caries prevention. PMID- 11205749 TI - Risk factors in patients after severe head injury. PMID- 11205750 TI - Caries intensity, salivary Streptococcus mutans and Lactobacillus counts in 12 year-old children. PMID- 11205751 TI - Own observations on the use of Esputicon to eliminate gases from the pancreatic area during ultrasound examinations. PMID- 11205752 TI - Health education of multiple sclerosis patients and their families. PMID- 11205753 TI - Spinal epidural abscess conservatively treated--a case report. PMID- 11205754 TI - Promotion of nursing services. PMID- 11205755 TI - Realising nursing function in neurological ward. PMID- 11205756 TI - The use of virtual 3D CT in diagnosing some intracranial diseases. PMID- 11205757 TI - The influence of ethanol and different free radical scavengers on the lipid peroxidation process and antioxidant status in the rats' gastric mucosa. PMID- 11205758 TI - Ultrastructural examination of hippocampal cells after experimental administration of dexamethasone. PMID- 11205759 TI - Neurotoxic effects of glucocorticosteroids--morphological examinations of hippocampal cells after experimental administration of dexamethasone. PMID- 11205760 TI - Selected cytokines and acute phase proteins in psoriatic patients treated with cyclosporin A or Re-PUVA methods. PMID- 11205761 TI - Knowledge of prevention of cardiovascular diseases in fourth-year students of Pedagogical and Psychological Faculty, Maria Curie-Sklodowska University in Lublin. PMID- 11205762 TI - [Importance of dynamic computed tomography in detecting and evaluating liver cavernous hemangioma]. AB - Dynamic sequential computed tomography (d-CT) was performed in 83 liver hemangiomas in 71 patients. In study group single lesions were present in 62 patients, 9 patients had two or more. In early phase (30-150 s) (79%) hemangiomas were peripherally hyperdense. In the delayed phase (2-7 min) 27% were totally hyperdense, 48% were isodense and 18% were of mixed density. We conclude that the contrast enhancement pattern of hemangiomas seen in dynamic computed tomography is useful in detecting and in differential diagnosis of these tumors. PMID- 11205763 TI - The influence of natrium fluoride on serum protein and cholesterol levels in rats with adriblastin-induced nephrotic syndrome. PMID- 11205764 TI - Dynamic hepatic CT: uniphasic and biphasic contrast medium injection protocols. PMID- 11205765 TI - Realisation of patients' rights in the Internal Diseases Department of the Provincial Specialistic Hospital in Lublin. PMID- 11205766 TI - Influence of hypoxia-induced convulsions on morphological structure of hippocampal cells. PMID- 11205767 TI - Knowledge of health consequences of nicotinism among secondary school pupils. Young people's attitudes towards passive smoking and their opinions about anti nicotine act's regulations. AB - The aim of the paper was to examine the level of knowledge of health conquences of nicotinism among secondary school pupils. It was also intended to determine what attitudes towards passive smoking and towards anti-nicotine act that is presently in force, they have. The results of the survey were analysed according to sex, class that the subjects attended and the fact if they were active smokers. PMID- 11205768 TI - Stress and methods of dealing with it among the students of the Faculty of Medicine of Medical University in Lublin. AB - The aim of the paper was to determine the level of stress sensibility of the students under examinations, to reconize its main causes as well as to determine what methods are used by students in order to overcome stress and how they evaluate the efficiency of these methods. The analysis of these kinds of behaviour according to such factors: sex, social background and temporary or permanent residence of the subject was carried out. PMID- 11205769 TI - Stress and methods of dealing with it among students of Arts Departments at the UMCS. AB - The aim of the paper was to determine the level of stress-perception for the students under examination, to recognise its main causes as well as to determine what methods are used by students in order to help them overcome stress. The analysis of these behaviours was carried out according to sex, social background and temporary or permanent residence of the subjects. The research results were confronted with similar survey carried out among students of the Faculty of Medicine at Medical University. PMID- 11205770 TI - Estimation of platelet activation and factor X activity in plasma of hypertensive patients. PMID- 11205771 TI - Morphological and clinical characteristics of renal cancers accidentally detected with ultrasound examination. PMID- 11205772 TI - tRNA of neoplastic tissues. PMID- 11205773 TI - Prevalence of various pathogens in patients treated in intensive care unit during the 7-year period. PMID- 11205775 TI - The correlation between activity and a circulating lymphocyte pattern in plasma of patients with psoriasis preceded by an infection. PMID- 11205774 TI - [Usefulness of current and retrospective markers of glycemia for early prognostication of ischemic stroke in diabetics and non-diabetics]. AB - Diabetes mellitus is associated with an increased incidence of ischaemic stroke but it is not established whether it may exacerbate its clinical course and prognosis. In the study we have assessed relations of fasting (1st-2nd day of illness) and pre-stroke glycaemia (measured as HbA1 and FA) with recent clinical manifestation and outcome within one month in 22 diabetics and 37 non-diabetics with ischaemic brain infarction in the internal carotid territory. Merely enhanced HbA1 in the majority of non-diabetic stroke patients confirmed impaired pre-stroke glucose tolerance but did not influence severity of hemiparesis and further prognosis. Abnormally high both HbA1 and dFA in diabetics, reflecting non sufficient metabolic control of illness did not exacerbate acute manifestation of stroke and outcome. Fasting post-stroke glycaemia that expresses a stress response of brain origin was determinative for clinical state but not for one month prognosis in diabetics and non-diabetics with brain infarction. PMID- 11205776 TI - Congenital malformations in children up to 1 year of age in the autopsy material from the Department of Pathomorphology, Medical Academy in Lublin in the years 1984-1998. PMID- 11205777 TI - Partial purification and characterization of enzymes degrading trehalose in mycobacteria. PMID- 11205778 TI - Proteolytic enzymes in the treatment of acute pancreatitis. PMID- 11205779 TI - Activity of cathepsins and morphological changes in the rat's liver after ranitidine and famotidine administration. PMID- 11205780 TI - Sudden deafness of vascular origin. PMID- 11205782 TI - Histo- and cytopathologic remote diagnosis (telepathology). Preliminary report. PMID- 11205781 TI - Evaluation of classes in medicine of catastrophe by students of Faculty of Medicine at the University School of Medicine in Lublin. PMID- 11205783 TI - CT imaging of the evolution of the post-traumatic intracerebral haematoma in children. PMID- 11205784 TI - Usefulness of CT in diagnosis of lung mycosis in children with acute leukemia. PMID- 11205785 TI - Analysis of mitochondrial tRNAs in hyperthyroidism. PMID- 11205786 TI - Serum sialic acid concentration and glycoprotein sialosylation in relation to temporary development of experimental alloxan induced diabetes in rabbits. PMID- 11205787 TI - Evaluation of occurrences of child maltreatment in teachers' opinions. AB - The fact of maltreatment is recorded in case of an intended or unintended action of the adult that has a negative influence on the child's health or psychophysical development. Apart from the term: mal-treatment a number of other terms are widely used: injuring, abuse, violence, harassment, ill-treatment. PMID- 11205788 TI - Social and medical factors of risk of premature births and prematurity. AB - The aim of the study is to estimate the influence of medical and social factors on the occurrence of premature births. PMID- 11205789 TI - The evaluation of the first period of the health service reform. AB - The aim of the study was to give preliminary estimation of functioning of the health service after the introduction of the reform on the basis of the opinions of the patients who used the services of the public health institutions. PMID- 11205790 TI - Evaluation of physical health of 14-year-old students attending primary schools in Lublin. PMID- 11205791 TI - Pulp stones in chambers of permanent molar teeth. PMID- 11205792 TI - The evaluation of root canal width by means of digital radiography. PMID- 11205793 TI - Vesico-intestinal fistulas, vesico-sigmoid fistula in the course of sigmoid cancer. PMID- 11205794 TI - Epilepsy associated with neoplastic brain tumours. A clinical study. PMID- 11205795 TI - Otoacoustic emission in dialysed children. PMID- 11205796 TI - Fascicular structure of the mixed nerves of the brachial plexus. PMID- 11205797 TI - Experimental studies of Tetric Ceram composite material and Syntac Sprint bonding system applied to dental pulp and hard tissues in rats. PMID- 11205798 TI - Changes in the excretion of glycosaminoglycans with urine in patients with kidney stones. PMID- 11205799 TI - Serum lipid profile in psoriatic females. PMID- 11205800 TI - Susceptibility to selected antibiotics of Streptococcus pneumoniae and Streptococcus pyogenes strains isolated from patients with respiratory tract infections. PMID- 11205801 TI - Cutaneous carcinoma in own investigations. PMID- 11205802 TI - A presentation of immunity against diphtheria in various age groups of Lublin population. PMID- 11205803 TI - Microsurgery and balneotherapy in the treatment of hyperplastic laryngitis. PMID- 11205804 TI - The effect of working environment on mucous membrane of the upper respiratory tract and organ of hearing in miners of the Lublin Coal mines. PMID- 11205805 TI - Ultrasonographic estimation of the size of spleen in children with psoriasis. PMID- 11205806 TI - [An unusual case of intracranial osteoma in a CT image]. AB - Osteomas are benign tumors that may cause life-threatening complications in intracranial localisation. A rare case of asymptomatic osteoma growing intracranially is reported. The review of literature on this subject is presented. PMID- 11205807 TI - Nucleolar organizer regions (NORs) as a prognostic factor in patients with squamous-cell oesophageal cancer. PMID- 11205808 TI - [Activity of malondialdehyde in rat plasma after H2 histamine receptor blockade]. AB - The study evaluates the effect of cimetidine (C), ranitidine (R) and famotidine (F) on the level of the plasma malondialdehyde (MDA). The tested drugs were given intraperitoneally to the male Wistar rats twice a day, during 6 weeks' period, in two doses. CI--2.85 mg/kg body weight (b.w.), R1--0.71 mg/kg b.w., F1--0.28 mg/kg b.w. The second doses (C2, R2, F2) were 10 times higher than C1, R1, F1. At the end of the 6th week of the experiment half of the animals were terminated. The remaining rats were kept for the next 6 weeks without any medications and were killed at the end of 12th week of the experiment. Blood was taken from still beating heart and centrifuged. The level of the MDA was determined from the plasma and compared to the 1 mg of the blood protein. None of administered H2 blockers changed the malondialdehyde level in serum of the experimental rats. PMID- 11205809 TI - Embryotoxic effect of low doses of caffeine. PMID- 11205811 TI - Development of nursing time standards as a problem of optimalisation of health care system management. I. Evaluation of the correctness of patients' classification. PMID- 11205810 TI - [Ultrasonographic diagnosis of Meckel's diverticulum--case report]. AB - Meckel's diverticulum is the congenital anomaly of the gastrointestinal tract affecting about 2% of the population. It is a true diverticulum containing all layers of the ileum wall. Heterotopic tissue is frequently present (25%): gastric mucosa, duodenal mucosa, jejunal mucosa and pancreatic tissue. Meckel's diverticulum is localized about 50 cm from the ileo-colic valve on the external border of the ileum. Most of Meckel's diverticula are clinically silent; clinical symptoms (19%) are in cases of complications such as: strangulation of the bowel in a ring formed by the diverticulum, intussusception of the diverticulum into the ileum, volvulus, incarceration of the diverticulum in hernia, tumour originating in the diverticulum. The diagnosis of Meckel's diverticulum is very difficult. The most useful in the diagnosis are plain abdominal radiographs, barium studies, CT, sonography and scintigraphy Abdominal sonography shows a tubular fluid structure localized far from the coecum. The wall of the diverticulum is swollen and in the lumen are chyme or fat. PMID- 11205812 TI - Development of nursing time standards as a problem of optimalisation of health care system management. II. Comparative analysis of demand for nursing care. PMID- 11205813 TI - The exhumation of a World War II Jewish grave. AB - The results of the exhumation of a mass grave from the time of the World War II are presented. In the course of exhumation it was established that the subjects were 190 individuals (men, women and children) of Jewish origin. All had died a violent death due to gunshot or mechanical injury. PMID- 11205814 TI - Immunological monitoring of chronic pleural empyema patients. PMID- 11205815 TI - Acute pulmonary effects of ultrafine particles in rats and mice. AB - Ambient fine particles consist of ultrafine particles (< 100 nm) and accumulation mode particles (approximately 100 to 1,000 nm). Our hypothesis that ultrafine particles can have adverse effects in humans is based on results of our earlier studies with particles of both sizes and on the finding that urban ultrafine particles can reach mass concentrations of 40 to 50 micrograms/m3, equivalent to number concentrations of 3 to 4 x 10(5) particles/cm3. The objectives of the exploratory studies reported here were to (1) evaluate pulmonary effects induced in rats and mice by ultrafine particles of known high toxicity (although not occurring in the ambient atmosphere) in order to obtain information on principles of ultrafine particle toxicology; (2) characterize the generation and coagulation behavior of ultrafine particles that are relevant for urban air; (3) study the influence of animals' age and disease status; and (4) evaluate copollutants as modifying factors. We used ultrafine Teflon (polytetrafluoroethylene [PTFE]*) fumes (count median diameter [CMD] approximately 18 nm) generated by heating Teflon in a tube furnace to 486 degrees C to evaluate principles of ultrafine particle toxicity that might be helpful in understanding potential effects of ambient ultrafine particles. Teflon fumes at ultrafine particle concentrations of approximately 50 micrograms/m3 are extremely toxic to rats when inhaled for only 15 minutes. We found that neither the ultrafine Teflon particles alone when generated in argon nor the Teflon fume gas-phase constituents when generated in air were toxic after 25 minutes of exposure. Only the combination of both phases when generated in air caused high toxicity, suggesting the existence of either radicals on the particle surface or a carrier mechanism of the ultrafine particles for adsorbed gas-phase compounds. We also found rapid translocation of the ultrafine Teflon particles across the epithelium after their deposition, which appears to be an important difference from the behavior of larger particles. Furthermore, the pulmonary toxicity of the ultrafine Teflon fumes could be prevented by adapting the animals with short 5-minute exposures on 3 days prior to a 15-minute exposure. This shows the importance of preexposure history in susceptibility to acute effects of ultrafine particles. Aging of the fresh Teflon fumes for 3.5 minutes led to a predicted coagulation resulting in particles greater than 100 nm that no longer caused toxicity in exposed animals. This result is consistent with greater toxicity of ultrafine particles compared with accumulation-mode particles. When establishing dose-response relationships for intratracheally instilled titanium dioxide (TiO2) particles of the size of the urban ultrafine particles (20 nm) and of the urban accumulation-mode particles (250 nm), we observed significantly greater pulmonary inflammatory response to ultrafine TiO2 in rats and mice. The greater toxicity of the ultrafine TiO2 particles correlated well with their greater surface area per mass. Ultrafine particles of carbon, platinum, iron, iron oxide, vanadium, and vanadium oxide were generated by electric spark discharge and characterized to obtain particles of environmental relevance for study. The CMD of the ultrafine carbon particles was approximately 26 nm, and that of the metal particles was 15 to 20 nm, with geometric standard deviations (GSDs) of 1.4 to 1.7. For ultrafine carbon particles, approximately 100 micrograms/m3 is equivalent to 12 x 10(6) particles/cm3. Homogeneous coagulation of these ultrafine particles in an animal exposure chamber occurred rapidly at 1 x 10(7) particles/cm3, so that particles quickly grew to sizes greater than 100 nm. Thus, controlled aging of ultrafine carbon particles allowed the generation of accumulation-mode carbon particles (due to coagulation growth) for use in comparative toxicity studies. We also developed a technique to generate ultrafine particles consisting of the stable isotope 13C by using 13C-graphite electrodes made in our laboratory from amorphous 13C powder. These particles are particularly useful tools for determining deposition efficiencies of ultrafine carbon particles in the respiratory tracts of laboratory animals and the translocation of particles to extrapulmonary sites. For compromised animals, we used acute and chronic pulmonary emphysema; a low-dose endotoxin inhalation aimed at priming target cells in the lung was also developed. Other modifying factors were age and copollutant (ozone) exposure. Exposure concentrations of the generated ultrafine particles for acute rodent inhalation studies were selected on the basis of lung doses predicted to occur in people inhaling approximately 50 micrograms/m3 urban ultrafine particles. Concentrations that achieved the same predicted lung burden per unit alveolar surface were used in rodents. (ABSTRACT TRUNCATED) PMID- 11205816 TI - Blood group phenotype distribution in Saudi Arabs. AB - The distribution of eight blood phenotypes (ABO, Rh, MNSs Lutheran, Kell, Duffy, Kidd and Lewis) was determined in Saudi Arabs and compared with corresponding published information for Caucasians and Negroes of United States of America, Saudi Arabs manifest ABO phenotype distribution similar to Negroes; rhesus phenotypes similar to Caucasians but an MNSs pattern largely distinct. Heterozygous Kell phenotype, Kk, was much more frequent in Saudi Arabs than in either Caucasians, or Negroes. The Kidd system null allete, JKa-b- was not seen in the studied group. However, increased frequencies of null alleles of the Duff (Fya-b-) and Lewis (Le(a-b-)) systems were observed in Saudi Arabs. PMID- 11205817 TI - Serum zinc, copper and magnesium in sickle cell disease at Ibadan, south western Nigeria. AB - Serum zinc, copper and magnesium were studied in patients with sickle cell disease in the steady state. There was significantly lower serum zinc concentration (P < 0.01) and significantly higher serum copper and magnesium in haemoglobin S patients compared with controls (HbA). In haemoglobin SC patients, there was a significant reduction in serum zinc (P < 0.01) but no significant difference in serum copper and magnesium concentrations compared with the controls. There was no significant difference in serum zinc concentration between the HbS and HbS + C patients. However there were significantly higher serum copper and magnesium in HbS than HbS + C patients (P < 0.01) The level of serum zinc has no correlation with the steady state Haematocrit or severity index score in HbS and HbS + C patients. PMID- 11205818 TI - Oral squamous cell carcinoma: a review of 246 Nigerian cases. AB - A review of 246 Nigerians with oral squamous cell carcinoma seen at the University College Hospital, Ibadan, over a 20-year (1976-1995) period was carried out. A prevalence rate of 1.2% was found with a male to female ratio of 1.5:1. Their ages ranged from 20 to 88 years with mean and median ages of 53.7 and 55.5 years respectively. The most common site was the palate while the least common was the buccal mucosa. Most patients presented later for treatment with advanced disease, but women tended to report earlier than men. Out of 125 patients who had definitive treatment, only 33 (26%) had adequate follow-up records and recurrence was noted in 13 (39%). The prevalence of oral squamous cell carcinoma is significant in this environment but patient awareness is still low. There is a need to step up awareness campaign programmes, provide more centres for cancer treatment and introduce mass screening programmes. PMID- 11205819 TI - Electrophysiological effects of chilotoquine on tight junctions of immature rat Sertoli cells in vitro. AB - We investigated the effect of CQ, an antimalarial drug with antiprotease activity, and NH4Cl, a related amines on the development of intercellular tight junctions in cultured immature rat Sertoli cells. Sertoli cells were seeded in serum-free defined medium at a density of 3 x 10(6) cells/0.64 cm2/well on Matrigel-covered Millicell-HA filters. CQ (1 microM and 2 microM) or NH4Cl (6.25 mM and 12 mM) was added to the outer (basal) compartment of the bicameral system either on day 1 or day 7 of the culture. Formation of tight junctions was monitored by measurement of the transepithelial resistance (TER) at 24 hr intervals using an impedance meter. TER in untreated controls was 50 omega/cm2 on day 1, increased progressively to 80 omega/cm2 by day 7 and plateaued until day 12. The cells treated from day 1 with CQ showed dose-dependent progressive increase in TER until day 12, reaching 191 omega/cm2 in cells treated with 1 microM concentration. In cells treated with CQ starting from day 7 of culture onwards, TER patterns were similar to those noted following exposure to chloroquine from day 1. Also in cultures containing NH4Cl, in comparison to the control, the increase in TER was significantly higher. These observations demonstrate that CQ and HN4Cl promote tight junction formation between immature rat Sertoli cells invitro suggesting that antiproteases may be involved in the formation of blood-testis barrier. PMID- 11205820 TI - Efficacy of pefloxacin in the treatment of postoperative sepsis in gynaecology. AB - Twenty four women with postoperative sepsis following gynaecological surgery were recruited into a study designed to determine the efficacy of Pefloxacin. With the standard oral dose of Pefloxacin, clinical cure or improvement occurred in 98% of the patients. In-vitro, 90% of bacterial isolates were sensitive to Pefloxacin. No adverse effect was encountered in any of the patients. We concluded that Pefloxacin is effective in the treatment of postoperative bacterial infections following gynaecological surgery. PMID- 11205821 TI - Estimation of plasma uric acid in pregnancy induced hypertension (PIH). Is the test still relevant? AB - Plasma uric acid and creatinine were estimated at each visit of 59 consenting women attending ante-natal clinic. Results in the third trimester of pregnancy confirmed that the plasma uric acid was able to differentiate between normal pregnancy and those with PIH at P < 0.002. The results of those with ordinary hypertension and the women who developed pre-eclampsia were similar. Plasma creatinine was found to be able to differentiate between women with ordinary hypertension (97.45 +/- 25.03 umol/L) and those with pre-eclampsia (288.75 +/- 191.97 umol/L) at P < 0.01. For patients with pre-eclampsia who developed convulsions, there invariably was a further rise in the plasma uric acid levels. Monitoring of plasma creatinine level among patients with PH will help to predict those at risk of developing pre-eclampsia. In the same way, monitoring of plasma uric acid level in those with pre-eclampsia will help to predict those that will develop eclampsia. The tests are inexpensive but sensitive, which is in contrast to many more expensive electronic alternatives. PMID- 11205822 TI - Prevalence of gall stones in a group of antenatal women in Ibadan, Nigeria. AB - The prevalence of gall stones in Africa is low even though this varies from one part of the continent to another. The few studies were hospital based and excluded majority of silent stones. Abdominal ultrasounds were carried out prospectively on 4,214 consecutive patients referred to an ultrasound centre which cares primarily for pregnant women--a well known vulnerable group for gall stones. An overall prevalence rate of 2.1% was found. This represents a 300-fold increase over previous figures in Ibadan albeit from a different study group. A further study of the disease in the general population is necessary, though it is suggested that the figure in the general population may be less. When this figure is compared with the 10 to 20% in Europe and North America, it confirms the low incidence of the disease in our environment. Majority of the stones were asymptomatic (95%). This needs to be confirmed in the general population. The average stone former in our environment as in previous study does not conform to the classical caucassian description. PMID- 11205823 TI - Anaesthetic manpower development in West Africa. AB - Advances in surgery have been possible worldwide largely due to specialized manpower, innovations in modern anaesthetic techniques and drugs. Shortage of specialist manpower in anaesthesia has continued in West Africa despite various available local postgraduate training programmes. This paper examines the impact of the West African Postgraduate Medical College (WAPMC) training programme on anaesthetic manpower development in the West Africa subregion. Data collected from the records of the WAPMC revealed that from April 1992 to October 1996 a total number of 2,963 candidates attempted the primary examination of the various surgical faculties compared to 93 candidates for anaesthesia--a ratio of 32 prospective surgeons to one anaesthetist. The end point of the training produced 292 Fellows in the five-year period with only six in anaesthesia, i.e., 1 anaesthetist to 49 surgeons. Although the diploma programme of the same College produced 56 graduates in the study period, 53.6% of them were pursuing the Fellowship programme in tertiary institutions. Suggestions are proposed to redress the ever-widening gap between the number of specialist surgeons and anaesthetists in the West Africa subregion. PMID- 11205824 TI - Antimicrobial screening of Bridelia, micrantha, Alchormea cordifolia and Boerhavia diffusa. AB - This report is on the antimicrobial potential of Bridelia micrantha, Alchornea cordifolia and Boerhavia diffusa sourced from traditional healers through an ethnobotanical survey of antiinfective plants in Egbado South in Ogun State, Nigeria. Extracts of B. micrantha and A. cordifolia exhibited significant inhibitory activity against the pathogenic organisms. In some cases, the antibacterial activity was comparable to those of ampicillin and gentamycin. However, only the leaf of A. cordifolia showed reasonable antifungal activity when compared with Trosyd. The study shows that there is justification for the use of these medicinal plants in traditional medicine. PMID- 11205826 TI - Levels of complement components, immunoglobulins and acute phase proteins in plasma during aging in Nigeria. AB - Plasma samples from Nigerians aged 6-95 years were examined for their content of complement components (C3, C4, factor B-Bf), immuloglobins (IgG, IgA, IgM IgD) and acute phase proteins (transferrin, albumin, C-reactive protein--CRP, alpha-2 macroglobulin). Albumin, was estimated colorimetrically and the other components by the single radial immunodiffusion techniques. No significant age-related changes in mean values of the four immunobulins and the four acute phase proteins could be demonstrated. Also, the mean values for C3 and Bf did not change significantly with age but C4 values rose significantly with increasing age (r 0.232: P < 0.01). PMID- 11205825 TI - The antihyperglycamic effect of Telfaria occidentalis in mice. AB - The hypoglycemic effect of Telfaria occidentalis was studied in mice. The effect of the aqueous extract of the leaves on blood glucose level were assessed in normoglycaemic, glucose induced hyperglycaemic and streptozotocin (STZ) induced diabetic mice. The aqueous extract given orally in 1 g/kg did not alter the blood glucose level in normoglycaemic mice. In glucose-induced hyperglycemia, antidiabetic activity was seen when the extract and glucose were administered simultaneously and when the extract was giving to the mice 60 minutes before glucose. In STZ-induced diabetic mice, a reduction in the blood glucose level was seen from day two of the administration of the extract. The hypoglycemic effect of the aqueous extract was compared with that of an oral dose of chlorpropamide (200 mg/kg) under the same conditions. The results of this study indicate that the aqueous extract of the leaves of Telfaria occidentalis possess hypoglycaemic activity. PMID- 11205827 TI - Crystal deposition in normal and diseased articular cartilage: an extended report. AB - Particles observed on the surfaces of human articular cartilage following trauma and from chondromalacic, osteoarthritic and rheumatoid joints using the scanning electron microscope were analysed by x-ray diffraction technique. The particles contained calcium and phosphorus and they were identified only in structurally abnormal cartilage. These findings suggest that local abnormality of articular cartilage probably underlies crystal-deposition. PMID- 11205828 TI - Routine antenatal syphilis screening--a case against. AB - To highlight the deficiencies associated with the routine antenatal syphilis screening as it is done now in the University College Hospital, Ibadan, and determine the cost effectiveness or otherwise of syphilis screening using as parameters the specificity of the method of screening as well as the gravity of the disease. The results of VDRL tests performed on pregnant women attending the antenatal clinic of the University College Hospital, Ibadan, in a 10-year period, January 1988 to December 1997 were analysed for seropositivity as well as congenital syphilis. The case notes of 110 sero-reactive patients were retrieved and analysed for pregnancy outcome. The prevalence rate of seropositive patients was 1.1%. Only 3 of the seropositive had repeated tests and were treated empirically with high doses of penicillin. There was no case of congenital syphilis. This study has shown that the syphilis screening as it is done now is not cost-effective. If VDRL test is to be continued, efforts must be made to reintroduce TPHA-test, which is more specific-specificity; it wastes a lot of time and money of the patients. Hence it is not cost effective. If VDRL test is to be continued efforts must be made to reintroduce TPHA-test, which is more specific. PMID- 11205829 TI - Radiological ageing process in the cervical spine of Nigerian women. AB - The study was designed to determine the age of commencement of ageing process in Nigerian women Four hundred (400) consecutive women requesting for cervical spine radiographs where recruited for this study. A study chart was made showing different variables like osteoarthrosis, detached osteophytes, postural ulterations and disk degenerations in a four year period from 1st January, 1993 to 31st December, 1996 the modified Kellgren and Lawrence grading system was used to assess radiographic changes. The highest rate of osteoarthrosis (31.13%) was found in the fifth decade. Incidence of postural alterations of the cervical spine rose sharply in the 5th and 6th decades of life. Grade 2 osteoarthrosis (Kellgren and Lawrence) was commonest (61.3%); Grades 3 and 4 had the lowest incidence (3.45%). Disc degeneration was commonest in the 5th; the most involved disc was C5/C6 and the least involved was C2/C3. It is concluded that the ageing process in the Nigerian women commences in the fourth decade of life, and apparently shows no difference with caucasian women. PMID- 11205830 TI - Intra-operative antibiotic bead maker--point of technique. AB - Chronic osteomyelitis is a disease of soft tissue and bone and it is common in the developing countries. The management of this debilitating disease requires the delivery of the appropriate chemotherapeutic agent at the site of the infection after adequate debridement. The search for a suitable carrier for these chemotherapeutic agents is the advent of the 'septopal' or gentamycin polymethylmethacrylate (gentamycin-PMMA) beads. Septopal beads are expensive and are not affordable by patients in the developing countries. Moreover, most of the micro-organisms (mixed flora) responsible for chronic osteomyelitis in our hospitals are sensitive to ceftriaxone and only in a few cases were gentamycin sensitive micro-organisms isolated. Therefore, it was imperative that patient specific and antibiotic-specific PMMA beads would be the way forward and this is the reasoning behind the production of the intra-operative antibiotic bead maker (IABM) and the point of technique is hereby presented. PMID- 11205831 TI - Effects of cold application on isometric strength and endurance of quadriceps femoris muscle. AB - This study was carried out to investigate the effect of cold therapy on isometric strength and endurance of the quadriceps femoris muscle group. Sixty volunteer healthy normal subjects participated in the study, 30 were males and 30 were females. They were aged between 20 and 27 years. The subjects were screened for previous knee injuries or abnormalities through history taking and physical examination. The baseline isometric strength and endurance of the quadriceps was tested before application of cold on the thigh. Immediate post and 10-minute post cold application isometric strength and endurance were measured using an adapted cable tensiometer. The result of the study showed that cold increased the isometric strength of the quadriceps in all the subjects immediate post and 10 minute post cold application (P < 0.05) and the immediate post cooling endurance index of male and combined male and female subjects (P < 0.05). No significant increase was seen in the immediate post cooling endurance for female subjects (P > 0.05). Also no significant difference was seen in 10-minute post cooling endurance of all the subjects when compared with the pre-cooling endurance. This study therefore concluded that cold application increased isometric muscle strength and endurance post cold application. It was therefore recommended that application of cold on muscle should be employed while rehabilitating an individual with musculoskeletal pathology or deficit particularly while training for muscle endurance, strength and restoration of muscle function. PMID- 11205832 TI - Gastric outlet obstruction in Maiduguri. AB - In a review of sixty-four (64) cases of gastric outlet obstruction (G.O.O.) seen at the University of Maiduguri Teaching Hospital between 1991 and 1996, cicatrising chronic duodenal ulcer accounted for 65.7% of cases, followed by antral carcinoma of the stomach 15%, congenital hypertrophic pyloric stenosis 9.4%, carcinoma of the head of pancreas 6% and congenital bands 3%. The usual presentations were forceful vomiting in a patient with background history of dyspepsia of varying duration depending on cause, visible persistalsis, weight loss, abdominal masses and electrolyte imbalances. Diagnoses was easy clinically and confirmed by barium studies and/or gastroduodenoscopy. Treatment offered depended on the cause of gastric outlet obstruction. PMID- 11205833 TI - Oral complications of cancer treatment. AB - This report describes the oral complications that may occur in patients who have undergone radiotherapy of the head and neck for the treatment of cancer. It highlights modalities available for reducing and managing these treatment-related consequences. It also discusses the difficulties encountered by the dental health professional providing care for these patients. PMID- 11205834 TI - Intravesical Lippes loop following insertion for the treatment of Asherman's syndrome: a case report. AB - A case report of a 36-year-old Para 6+0 (1 alive) civil servant who developed Asherman's syndrome following repair of ruptured uterus is presented. She had adhesiolysis and insertion of Lippes loop. She defaulted 3 months after presentation and was seen 1 year after with intravesical translocation of the IUCD. This was successfully removed using a forward biting bladder biopsy forceps under direct cystoscopic view. PMID- 11205835 TI - Potency status and efficacy of measles vaccine administered in Nigeria: a case study of three EPI centres in Lagos, Nigeria. AB - The potency status and efficacy of measles vaccines were studied in three immunization (EPI) centres in the suburban area of Lagos, Nigeria. A total of 14 vials of measles vaccine were collected and subjected to potency testing while, 203 measles-vaccinated children were recruited for this study. Only 85 (41.87%) of the vaccinees reported back for the post-vaccination follow-up screening. The seroconversion pattern showed that 51(60%) had potent antibody titres ranging from 1:40 to 1:1280, while the remaining 34 (40%) had a low antibody titres between < 1:20 and 1:20. The vaccine potency test showed that only 1 (7.14%) of the 14 vaccine vials collected at these centres had virus titre of 3.5 Log while the remaining 13 (92.86%) had virus titres lower than 3.0 Log: the recommended human dose by the World Health Organisation (WHO) for measles vaccine. The administration of these subpotent and/or impotent vaccines vis-a-vis the status of immune response elicited in the vaccinees may be one of the reasons for the occurrence of measles infection in vaccinated children in the recent time in Nigeria. We herein suggested the subjection of all vaccines to a thorough standard laboratory screening before use in Nigeria. PMID- 11205836 TI - Diagnostic value of alpha 1-fetoprotein and beta-human chorionic gonadotropin in infancy and childhood. AB - This article provides a comprehensive review of the current literature and summarizes the experience of the German cooperative protocols for nontesticular germ cell tumors (MAKEI) on the use of alpha 1-fetoprotein (AFP) and beta-human chorionic gonadotropin (beta-hCG) for diagnostic evaluation in pediatric oncology. Based on this evaluation, this review proposes guidelines for the initial diagnostic work-up for children with clinically suspected secreting tumors. AFP and beta-hCG represent the characteristic tumor markers of malignant epithelial liver tumors and malignant germ cell tumors (GCT). They play an important role in the initial diagnostic evaluation as well as in the follow-up examination during therapy. Current therapeutic strategies for both tumor types include preoperative chemotherapy followed by delayed tumor resection. Therefore, it is essential for the pediatrician in charge to be aware of the broad differential diagnosis of elevated AFP and beta-hCG. In a well-defined clinical setting, these tumor markers allow clinical diagnosis without histological confirmation, but the physiologically elevated AFP serum levels in infancy or unrecognized benign conditions, such as hepatic diseases or hereditary disorders, must also be considered as differential diagnoses. Therefore, the laboratory investigations should include liver parameters in all patients to exclude hepatic disease. In addition, pregnancy must be excluded in adolescents. Careful history taking and clinical examination will further help to rule out metabolic disorders or ataxia teleangiectasia that are associated with elevated AFP levels. Having excluded these conditions, elevated AFP levels above the age-related normal range (with or without high beta-hCG), indicate malignant epithelial liver tumors in primary liver lesions. At virtually all other sites, the diagnosis of a malignant GCT with a substantial yolk sac tumor and/or choriocarcinoma component can be established. Pancreaticoblastoma should be considered in the differential diagnosis of tumors of the upper abdomen, and biopsy must be performed. Other childhood tumors are rarely associated with AFP or beta-hCG production, usually at only moderately elevated serum levels, and in most patients these tumors can be excluded by clinical and radiological examination. PMID- 11205837 TI - Initial P-glycoprotein expression in childhood acute lymphoblastic leukemia: no evidence of prognostic impact in follow-up. AB - Treatment results in childhood acute lymphoblastic leukemia (ALL) have improved remarkably during the past 20 years, but still 25% of children cannot be permanently cured. Drug resistance is a major cause of poor outcome. One of the most investigated resistance mechanisms is the P-glycoprotein (P-gp)-mediated multiple-drug resistance (MDR). The authors prospectively analyzed P-gp using flow cytometry with monoclonal antibody JSB1 in a population-based series of 103 children with ALL treated according to intensive Nordic ALL protocols. Increased P-gp expression was detected in 55 patients (53%). With a cutoff value of 1% P-gp positive blasts in bone marrow, no difference was found in event-free survival (EFS) or overall survival between children with low vs. increased P-gp expression. The 4-year EFS in the whole series was 77%. Patients with T-ALL had higher P-gp levels than the others, 3.6% vs. 1.0% (p = .002). P-gp expression did not correlate with the white blood cell count, age, sex, or cytogenetics. The authors conclude that the level of P-gp expression cannot be used as a tool for treatment stratification in childhood ALL. PMID- 11205838 TI - Tumor suppressor genes on the short arm of chromosome 1 in neuroblastoma. PMID- 11205839 TI - P73 expression in neuroblastoma: a role in the biology of advanced tumors? AB - p73, a recently identified gene showing high homology to p53 and mapping to 1p36.33, was presented as a candidate gene for neuroblastoma. In this study the authors evaluate the levels and allelic nature of p73 expression in primary neuroblastomas using reverse transcription-polymerase chain reaction-restriction fragment length polymorphism strategies based on intragenic polymorphisms. From 32 neuroblastoma patients, 11 were heterozygous for the p73 polymorphisms analyzed. p73 expression was found to be low in the correspondent tumors and while all 6 stages 1 and 2 tumors presented biallelic expression, 4 out of the 5 stage 4 tumors showed only one active p73 allele. Analysis of blood samples from 8 healthy donors and 4 neuroblastoma patients revealed much higher levels of p73 expression, and exclusively of biallelic nature. These results are supportive of a role for p73 in the biology of neuroblastoma, particularly in some advanced tumors. Nevertheless, the G81A/C91T polymorphism, previously implicated in regulating the expression of p73, did not show any significant association with neuroblastoma development. PMID- 11205840 TI - Management of cutaneous hemangiomas: a retrospective analysis of 1109 cases and comparison of conventional dose prednisolone with high-dose methylprednisolone therapy. AB - The effectiveness of the different pharmacological agents and different doses of systemic corticosteroids was analyzed. A total of 1109 patients (median age 8 months; F/M: 2.3) with hemangioma, followed up in our unit for 23 years, were evaluated retrospectively. Forty-five of them received systemic corticosteroids. Two different pharmacological agents, prednisolone (in 26 patients) and methyl prednisolone (in 19 patients), had been used in three different regimens. Groups were compared according to the final results and rebound regrowth. Response was considered good or excellent in 16 patients (36%). Then were no differences in response to therapy among the three regimens. No difference was found in response to therapy between prednisolone and methylprednisolone and the two different doses of the methylprednisolone. Rebound regrowth was significantly higher in methyl prednisolone than in the prednisolone group (p = .045). In multivariate analysis the dimension of the lesion (p = .0065) and age at initiation of treatment (p = .0041) were the most important factors affecting the response. In conclusion, the systemic corticosteroids are effective in 36% of patients, independent of dosage and pharmacological agents and duration of the therapy. The dimension of the lesion and age at initiation of treatment are the most important factors affecting the response to treatment. PMID- 11205841 TI - Effect of two-round Ficoll-Hypaque density gradient centrifugation on lymphocyte subsets and natural killer activity of umbilical cord blood mononuclear cells. AB - Umbilical cord blood (CB) mononuclear cells (MNCs) obtained from Ficoll-Hypaque density gradient centrifugation (FDGC) are frequently contaminated with erythrocytes and nucleated erythroid precursors. The authors investigated the effect of two-round (2-r) FDGC on lymphocyte subsets and natural killer activity of CB and adult peripheral blood (APB) MNCs, in comparison with those obtained from conventional one-round (1-r) separation. The percentage of CD45-expressing CB MNCs was greatly increased after the second density step (p < .01), indicating the efficacy in purification. The percentages of CD3/CD4, CD3/CD8, and CD16/56 double-positive staining CB MNCs were significantly increased after 2-r FDGC, as compared to those after 1-r separation. However, the percentages of CD34+ stem cells and CD19+ B cells were not affected by 2-r FDGC. MNCs obtained from 2-r FDGC had higher natural killer (NK) activity than did MNCs obtained from 1-r separation (p < .01). In contrast, 2-r FDGC did not affect lymphocyte subsets and NK activity of APB MNCs as compared to 1-r FDGC. Thus, 2-r FDGC are recommended to obtain CB MNCs for flow cytometric analysis and NK cytotoxicity assays. PMID- 11205842 TI - Hemophagocytic lymphohistiocytosis associated with visceral leishmaniasis. AB - A 2-year-old child presented with fever and hepatosplenomegaly. Laboratory findings showed pancytopenia, hypertriglyceridemia, hyperferritinemia, and high levels of soluble-IL2 receptors. Initial bone marrow aspiration and biopsy revealed mild hemophagocytosis. A diagnosis of hemophagocytic lymphohistiocytosis was made and appropriate treatment was begun. Repeated marrow aspiration performed because of lack of clinical response revealed Leishmania amastigotes in macrophages in addition to active hemophagocytosis. Treatment with liposomal amphotericin resulted with rapid recovery. Visceral leishmaniasis should be considered in the differential diagnosis of hemophagocytic syndrome. PMID- 11205843 TI - University of Newcastle Upon Tyne: epidemiological studies of childhood cancer. PMID- 11205844 TI - Treatment of superior vena cava syndrome with recombinant tissue plasminogen activator in a sickle cell patient undergoing bone marrow transplantation. AB - Superior vena cava (SVC) syndrome is a well-recognized clinical entity seen with mediastinal malignancies and intraluminal venous thrombosis. The role of recombinant tissue plasminogen activator (rt-PA) in the resolution of SVC syndrome caused by thrombosis in the bone marrow transplant settings has not been described. The authors report a case of SVC syndrome with good clinical response in a 16-year-old female with sickle cell disease undergoing an allogeneic bone marrow transplant (BMT) from her HLA identical sibling. Shortly after her transplant, she was found to have significant facial edema and swelling above the neck. Concomitantly, her renal function deteriorated with progressive elevation of serum urea nitrogen and creatinine levels, requiring the use of continuous veno-venous hemofiltration. An upper extremity venogram showed complete SVC obstruction (type III) with apparent inferior reflux into the azygos system. rt PA was started at a dose of (0.5 mg/kg/day) for 2 days. There was a dramatic resolution of her symptoms, including significant improvement in renal function with increase in urine output. A repeat venogram showed free flow from the distal tip of the central line consistent with a patent superior vena cava. There was no evidence of any bleeding manifestations with rt-PA. This report highlights the usefulness of rt-PA as a treatment modality for SVC syndrome in the BMT settings. PMID- 11205845 TI - Hypertrophic osteoarthropathy and childhood Hodgkin disease. PMID- 11205846 TI - Intra-articular lipoma of the knee joint. A case report. PMID- 11205847 TI - Injuries of the posterolateral corner of the knee. AB - The complex anatomy of the posterolateral corner of the knee is due largely to the evolutionary changes in the anatomic relationships of the fibular head, the popliteus tendon, and the biceps femoris muscle. Recent research has improved our understanding of the popliteus complex, particularly the role of the popliteofibular ligament. Biomechanical studies provide a scientific basis for clinical examination of the knee with suspected injury of the posterolateral corner. All grade-I and most moderate grade-II injuries of the posterolateral structures can be treated nonoperatively, but residual laxity may remain, especially in knees with grade-II injury. Acute grade-III isolated or combined injury of the posterolateral corner is best treated early, by direct repair, if possible, or else by augmentation or reconstruction of all injured ligaments. Chronic injury of the posterolateral corner, whether isolated or combined, is probably best treated by reconstruction of the posterolateral corner along with reconstruction of any coexisting cruciate ligament injury. Failure to diagnose and treat an injury of the posterolateral corner in a patient who has a known tear of the anterior or posterior cruciate ligament can result in failure of the reconstructed cruciate ligament. PMID- 11205848 TI - The orthopaedic clinician-scientist. PMID- 11205849 TI - Repetitive stress injury. PMID- 11205850 TI - Repetitive stress injury. PMID- 11205851 TI - Inability to obtain formal informed consent in the face of a standard surgical indication. AB - A thirty-eight-year-old intoxicated man was admitted to the surgical trauma service following a single motor-vehicle accident. He had a severe closed head injury, bilateral pulmonary contusions, a fracture-dislocation of the right acetabulum, and an open injury of the right knee joint. The acetabular fracture pattern was an associated both-column fracture with the femoral head dislocated into a widely displaced posterior-column fracture line. The treating physicians agreed that it would be in the patient's best interest to take him to the operating room for emergent debridement and irrigation of his knee wound. At surgery, the patient also underwent attempted closed reduction of the acetabular fracture and placement of a skeletal traction pin. Radiographs obtained with the patient in traction showed reduction of the femoral head beneath a displaced superior dome fragment, but there remained a 12-mm gap in the posterior column, greater than 3 mm of step incongruity, and a large articular fragment entrapped in the anterior aspect of the hip joint. The patient remained intubated and sedated for several days. Upon weaning from the ventilator, it became evident that his head injury would prevent him from being able to give informed consent in the foreseeable future. The patient's family members refused to become involved with his care or medical decision-making, as he had become completely estranged from them as a result of his chronic alcohol abuse. Further delay in surgical treatment for the acetabular fracture would be associated with greater difficulty in obtaining an anatomic reduction, the potential for additional articular damage to the femoral head, and an increased risk of surgical complications. The question that arises is whether it is in the patient's best interest for the surgeon to proceed with open reduction and internal fixation of the acetabular fracture without having had the opportunity to fully inform him of the treatment options or the risks associated with an extensive surgical exposure. PMID- 11205852 TI - What's new in shoulder surgery. AB - The purpose of this update on shoulder surgery is to discuss, in summary fashion, topics presented at selected orthopaedic meetings during the time-period of August 1999 to July 2000. Sources for this article were presentations and symposia at meetings of the American Orthopaedic Society for Sports Medicine (Specialty Day, Orlando, Florida, March 2000, and the Twenty-sixth Annual Meeting, Sun Valley, Idaho, June 2000), the Arthroscopy Association of North America (Specialty Day, Orlando, Florida, March 2000, and the Nineteenth Annual Meeting, Miami, Florida, April 2000), the American Academy of Orthopaedic Surgeons (Sixty-seventh Annual Meeting, Orlando, Florida, March 2000), the American Shoulder and Elbow Surgeons (Specialty Day, Orlando, Florida, March 2000, and the Sixteenth Annual Meeting, Philadelphia, Pennsylvania, October 1999), and the American Orthopaedic Association (113th Annual Meeting, Hot Springs, Virginia, June 2000). PMID- 11205853 TI - Meta-analyses in orthopaedic surgery. A systematic review of their methodologies. AB - BACKGROUND: The number and quality of well-designed scientific studies in the orthopaedic literature are limited. The purpose of this review was to determine the methodological qualities of published meta-analyses on orthopaedic-surgery related topics. METHODS: A systematic review of meta-analyses was conducted. A search of the Medline database provided lists of meta-analyses in orthopaedics published from 1969 to 1999. Extensive manual searches of major orthopaedic journals, bibliographies of major orthopaedic texts, and personal files identified additional studies. Of 601 studies identified, forty met the criteria for eligibility. Two investigators each assessed the quality of the studies under blinded conditions, and they abstracted relevant data. RESULTS: More than 50% of the meta-analyses included in this review were published after 1994. We found that 88% had methodological flaws that could limit their validity. The main deficiency was a lack of information on the methods used to retrieve and assess the validity of the primary studies. Regression analysis revealed that meta analyses authored in affiliation with an epidemiology department and those published in nonsurgical journals were associated with higher scores for quality. Meta-analyses with lower scores for quality tended to report positive findings. The meta-analyses that focused upon fracture treatment and degenerative disease (hip, knee, or spine) had significantly lower mean quality scores than did meta analyses that examined thrombosis prevention and diagnostic tests (p < 0.05). CONCLUSIONS: The majority of meta-analyses on orthopaedic-surgery-related topics have methodological limitations. Limitation of bias and improvement in the validity of the meta-analyses can be achieved by adherence to strict scientific methodology. However, the ultimate quality of a meta-analysis depends on the quality of the primary studies on which it is based. A meta-analysis is most persuasive when data from high-quality randomized trials are pooled. PMID- 11205854 TI - Complications of elbow arthroscopy. AB - BACKGROUND: Although the potential complications of elbow arthroscopy, including nerve injuries, have been described, the prevalence of their occurrence has not been well defined. The purpose of this paper is to describe the serious and minor complications in a large series of patients treated with elbow arthroscopy. METHODS: A retrospective review of 473 consecutive elbow arthroscopies performed in 449 patients over an eighteen-year period was conducted. Of the 473 cases, 414 were followed for more than six weeks. The most common final diagnoses were osteoarthritis (150 cases), loose bodies (112), and rheumatoid or inflammatory arthritis (seventy-five). The arthroscopic procedures included synovectomy (184), debridement of joint surfaces or adhesions (180), excision of osteophytes (164), diagnostic arthroscopy (154), loose-body removal (144), and capsular procedures such as capsular release, capsulotomy, and capsulectomy (seventy-three). RESULTS: A serious complication (a joint space infection) occurred after four (0.8%) of the arthroscopic procedures. Minor complications occurred after fifty (11%) of the arthroscopic procedures. These complications included prolonged drainage from or superficial infection at a portal site after thirty-three procedures, persistent minor contracture of 20 degrees or less after seven, and twelve transient nerve palsies (five ulnar palsies, four superficial radial palsies, one posterior interosseous palsy, one medial antebrachial cutaneous palsy, and one anterior interosseous palsy) in ten patients. The most significant risk factors for the development of a temporary nerve palsy were an underlying diagnosis of rheumatoid arthritis (p < 0.001) and a contracture (p < 0.05). There were no permanent neurovascular injuries, hematomas, or compartment syndromes in our series, and all of the minor complications, except for the minor contractures, resolved without sequelae. CONCLUSIONS: Our results indicate that the prevalence of temporary or minor complications following elbow arthroscopy may be greater than previously reported. However, serious or permanent complications were uncommon. PMID- 11205855 TI - A prospective evaluation of the clinical utility of the lower-extremity injury severity scores. AB - BACKGROUND: High-energy trauma to the lower extremity presents challenges with regard to reconstruction and rehabilitation. Failed efforts at limb salvage are associated with increased patient mortality and high hospital costs. Lower extremity injury-severity scoring systems were developed to assist the surgical team with the initial decision to amputate or salvage a limb. The purpose of the present study was to prospectively evaluate the clinical utility of five lower extremity injury-severity scoring systems. METHODS: Five hundred and fifty-six high-energy lower-extremity injuries were prospectively evaluated with use of five injury-severity scoring systems for lower-extremity trauma designed to assist in the decision-making process for the care of patients with such injuries. Four hundred and seven limbs remained in the salvage pathway six months after the injury. The sensitivity, specificity, and area under the receiver operating characteristic curve were calculated for the Mangled Extremity Severity Score (MESS); the Limb Salvage Index (LSI); the Predictive Salvage Index (PSI); the Nerve Injury, Ischemia, Soft-Tissue Injury, Skeletal Injury, Shock, and Age of Patient Score (NISSSA); and the Hannover Fracture Scale-97 (HFS-97) for ischemic and nonischemic limbs. The scores were analyzed in two ways: including and excluding limbs that required immediate amputation. RESULTS: The analysis did not validate the clinical utility of any of the lower-extremity injury-severity scores. The high specificity of the scores in all of the patient subgroups did confirm that low scores could be used to predict limb-salvage potential. The converse, however, was not true. The low sensitivity of the indices failed to support the validity of the scores as predictors of amputation. CONCLUSIONS: Lower-extremity injury-severity scores at or above the amputation threshold should be cautiously used by a surgeon who must decide the fate of a lower extremity with a high-energy injury. PMID- 11205856 TI - The effect of upper-limb motion on lower-limb muscle synchrony. Implications for anterior cruciate ligament injury. AB - BACKGROUND: A high prevalence of rupture of the anterior cruciate ligament is associated with activities that incorporate both abrupt deceleration and catching a ball. In the present study, we examined whether the upper-limb motion involved in catching a ball affected the synchrony of the lower-limb muscles during tasks known to stress the anterior cruciate ligament-namely, abrupt decelerative landings. METHODS: Seven male and eleven female subjects decelerated abruptly to land in single-limb stance after catching a chest-height pass and after no catching. Ground-reaction force and electromyographic data for six lower-limb muscles were sampled while the subjects' landing technique was filmed. The joint reaction forces and the sagittal planar net moments for the knee then were calculated to derive the tibiofemoral shear forces. The muscle onsets and peak muscle activities were temporally analyzed with respect to the time of initial foot-ground contact, the peak resultant ground-reaction force, and the peak tibiofemoral shear force. RESULTS: When catching a pass, the subjects demonstrated significantly (p < 0.05) earlier rectus femoris onset relative to the timing of the initial foot-ground contact and of the peak tibiofemoral shear force, and they showed delayed biceps femoris onset relative to the timing of the peak tibiofemoral shear force compared with the findings in the trials without catching. CONCLUSIONS: We concluded that catching a ball during an abrupt landing could increase the potential for an anterior cruciate ligament injury by limiting the time available for the hamstring muscles to generate posterior tibial-drawer force before the onset of the quadriceps-induced anterior tibial translation. CLINICAL RELEVANCE: The integrity of the anterior cruciate ligament during landing relies on the proper coordination of the lower-limb muscles, particularly the quadriceps and the hamstrings. The present study demonstrated that motion of the upper-limbs may interfere with recruitment of these muscles, thereby predisposing the anterior cruciate ligament to injury. PMID- 11205857 TI - Measurement accuracy in congenital scoliosis. AB - BACKGROUND: The accuracy of measurement of curves in idiopathic scoliosis has been extensively studied; however, we know of only one article in the literature concerning the accuracy of measurement of curves in congenital scoliosis. That article stated that intraobserver variability was +/- 9.6 degrees and interobserver variability was +/- 11.8 degrees. METHODS: Sixty-nine curves in fifty patients with congenital scoliosis were measured on two separate occasions by seven different observers with varying experience in curve measurement. RESULTS: Mean intraobserver variance ranged from 1.9 degrees to 5.0 degrees, with an average of 2.8 degrees (95% confidence limit, +/- 3 degrees) for the seven observers. The interobserver variance was 3.35 degrees (95% confidence limit, 7.86 degrees). CONCLUSIONS: It is possible to measure curves in congenital scoliosis with much greater accuracy than previously reported. In the clinical situation in which a skilled observer can measure two radiographs at the same time, an accuracy of +/- 3 degrees can be expected 95% of the time. PMID- 11205858 TI - Damage to cobalt-chromium surfaces during arthroscopy of total knee replacements. AB - BACKGROUND: It has been stated that care must be taken not to scratch the metal components during total knee arthroscopy; however, this concern has not been studied. Clinical observation during arthroscopy of total knee replacements suggested the possibility of damage to the femoral component by the arthroscopic cannula; therefore, a bench test was performed to study this potential risk. METHODS: Cobalt-chromium femoral components were tested to determine the surface damage that resulted from moving a stainless-steel arthroscopic cannula and a plastic arthroscopic cannula across the components under a variety of applied loads. Scanning electron microscopy and surface-roughness measurements of the prosthetic surface were used to evaluate the damage. RESULTS: The stainless-steel cannula produced observable alterations to the surface of the femoral component at loads as small as 8 N. The majority of these alterations were deposits of stainless steel from the cannula onto the component. The plastic cannula did not appear to produce alterations on the component surface. Surface roughness increased with increasing loading of the stainless-steel cannula, but there was no noticeable change with increasing loading of the plastic cannula. These forces did, however, severely damage some parts of the plastic cannula. CONCLUSIONS: Alterations to the surface of cobalt-chromium femoral components can occur during arthroscopy with stainless-steel cannulae but not with plastic cannulae. The results of this study support a recommendation to use plastic cannulae during arthroscopy of total knee replacements. CLINICAL RELEVANCE: Arthroscopy of total knee replacements is increasing in the clinical setting, and damage to the prosthesis should be avoided whenever possible. This study provides evidence that damage to the femoral component is possible with a stainless-steel cannula and that use of a plastic cannula may reduce this risk. PMID- 11205859 TI - Spontaneous repair of full-thickness defects of articular cartilage in a goat model. A preliminary study. AB - BACKGROUND: Full-thickness defects measuring 3 mm in diameter have been commonly used in studies of rabbits to evaluate new procedures designed to improve the quality of articular cartilage repair. These defects initially heal spontaneously. However, little information is available on the characteristics of repair of larger defects. The objective of the present study was to define the characteristics of repair of 6-mm full-thickness osteochondral defects in the adult Spanish goat. METHODS: Full-thickness osteochondral defects measuring 6 x 6 mm were created in the medial femoral condyle of the knee joint of adult female Spanish goats. The untreated defects were allowed to heal spontaneously. The knee joints were removed, and the defects were examined at ten time-intervals, ranging from time zero (immediately after creation of the defect) to one year postoperatively. The defects were examined grossly, microradiographically, histologically, and with magnetic resonance imaging and computed tomography. RESULTS: The 6-mm osteochondral defects did not heal. Moreover, heretofore undescribed progressive, deleterious changes occurred in the osseous walls of the defect and the articular cartilage surrounding the defect. These changes resulted in a progressive increase in the size of the defect, the formation of a large cavitary lesion, and the collapse of both the surrounding subchondral bone and the articular cartilage into the periphery of the defect. Resorption of the osseous walls of the defect was first noted by one week, and it was associated with extensive osteoclastic activity in the trabecular bone of the walls of the defect. Flattening and deformation of the articular cartilage at the edges of the defect was also observed at this time. By twelve weeks, bone resorption had transformed the surgically created defect into a larger cavitary lesion, and the articular cartilage and subchondral bone surrounding the defect had collapsed into the periphery of the defect. By twenty-six weeks, bone resorption had ceased and the osseous walls of the lesion had become sclerotic. The cavitary lesion did not become filled in with fibrocartilage. Instead, a cystic lesion was found in the center of most of the cavitary lesions. Only a thin layer of fibrocartilage was present on the sclerotic osseous walls of the defect. Specimens examined at one year postoperatively showed similar characteristics. CONCLUSIONS: Full thickness osteochondral defects, measuring 6 mm in both diameter and depth, that are created in the medial femoral condyle of the knee joint of adult Spanish goats do not heal spontaneously. Instead, they undergo progressive changes resulting in resorption of the osseous walls of the defect, the formation of a large cavitary lesion, and the collapse of the surrounding articular cartilage and subchondral bone. CLINICAL RELEVANCE: As surgeons apply new reparative procedures to larger areas of full-thickness articular cartilage loss, we believe that it is important to consider the potential deleterious effects of a "zone of influence" secondary to the creation of a large defect in the subchondral bone. When biologic and synthetic matrices with or without cells or bioactive factors are placed into surgically created osseous defects, the osseous walls serve as shoulders to protect and stabilize the preliminary repair process. It is important to protect the repair process until biologic incorporation occurs and the chondrogenic switch turns the cells on to synthesize an articular-cartilage like matrix. It takes a varying period of time to fill a large, surgically created bone defect underlying a chondral surface. The repair of such a defect requires bone synthesis and the reestablishment of a subchondral plate with a tidemark transition to the new overlying articular surface. The prevention of secondary changes in the surrounding bone and articular cartilage and the durability of the new reparative tissue making up the articulating surface are issues that must be addressed in future studies. PMID- 11205860 TI - Initial review of Electronic Residency Application Service charts by orthopaedic residency faculty members. Does applicant gender matter? AB - BACKGROUND: Orthopaedic surgery is a male-dominated field. As of 1998, women accounted for 42% of medical school graduates, yet only 6.9% of the total number of orthopaedic residents were female. The purpose of our study was to determine whether the Electronic Residency Application Service charts of female candidates for orthopaedic residencies are ranked lower by faculty reviewers than are those of male candidates with similar qualifications. METHODS: After we obtained permission from the applicants, the Electronic Residency Application Service applications submitted by ninety male and ten female candidates for admission to a university orthopaedic residency program for the 1998 National Residency Matching Program were randomly divided into ten groups, consisting of the charts of nine male candidates and one female candidate. Each chart from a female candidate was altered into a "male" version, in which all names and personal pronouns were changed but which was otherwise identical to the original female version. Therefore, each group of ten charts existed as a paired set: one containing the true female chart and one, the altered "male" chart. The paired sets acted as their own control. One hundred and twenty-one faculty reviewers from fourteen orthopaedic residency programs around the United States each reviewed either the "male" or the female version of one set, without knowledge of the goals of the study, and ranked the ten charts in the order in which they would like to have the candidates as residents in their own programs. Each version of the sets was reviewed by at least five separate reviewers. Reviewers at a given institution were randomized to review different sets, so that there was no overlap among them. The rankings of the female-"male" pairs were compared with use of a standard paired t test. RESULTS: No significant difference was detected in the rankings of the female and "male" charts (p = 0.5). The mean difference in rankings was -0.33, with a 95% confidence interval ranging from 1.41 (favoring females) to 0.74 (favoring "males"). CONCLUSIONS: The low percentage of female residents is not due to bias against female applicants in the initial chart-review phase of the orthopaedic residency selection process. It is possible that bias is introduced in other stages of the selection process, such as the interview. PMID- 11205861 TI - Surgical repair of chronic rotator cuff tears. A prospective long-term study. AB - BACKGROUND: Rotator cuff disease or injury is one of the most frequently seen orthopaedic conditions, and surgical repair of rotator cuff tears is a common procedure. A prospective analysis of the operation, with consistent assessment of patient characteristics, variables associated with the rotator cuff tear and repair techniques, and outcome factors, was performed. METHODS: One hundred and five shoulders with a chronic rotator cuff tear underwent open surgical repair and acromioplasty between 1975 and 1983. The patients were followed for an average of 13.4 years (range, two to twenty-two years). There were sixteen small tears, forty medium tears, thirty-eight large tears, and eleven massive tears. The tears were repaired directly (seventy-two tears), by V-Y plasty (twelve), by tendon transposition (twenty), or by reinforcement with a fascia lata graft (one). The long head of the biceps had been previously torn in eleven shoulders and was tenodesed in three other shoulders. In fifty-six shoulders, the distal part of the clavicle was excised for treatment of degenerative arthritic changes, often associated with osteophyte formation. RESULTS: Satisfactory pain relief was obtained in ninety-six shoulders (p < 0.0001). There was significant improvement in active abduction (p < 0.001) and external rotation (p < 0.007) as well as in strength in these directions of movement (p < 0.03 and p < 0.002, respectively). At the latest follow-up evaluation, the result was rated as excellent for sixty eight shoulders, satisfactory for sixteen, and unsatisfactory for twenty-one. Tear size was the most important determinant of outcome with regard to active motion, strength, rating of the result, patient satisfaction, and need for a reoperation. Older age, less preoperative active motion, preoperative weakness, distal clavicular excision, and a transposition repair technique were all associated with larger tear size. There were eight reoperations; five were for rerepair of a persistent or recurrent rotator cuff tear. CONCLUSIONS: Standard tendon repair techniques combined with anterior acromioplasty, postoperative limb protection, and monitored physiotherapy can produce consistent and lasting pain relief and improvement in range of motion. Improving the results of this procedure will depend upon the development of new techniques to address the active motion and strength deficiencies following repair of massive rotator cuff tears. PMID- 11205862 TI - Resection, rotationplasty, and femoropelvic arthrodesis in severe congenital femoral deficiency. A report of the surgical technique and three cases. AB - BACKGROUND: The major problems associated with severe congenital deficiency of the femur are an unstable hip joint and a femur that is more than 50% shorter than the contralateral, normal femur. The usual treatment of these extreme cases of congenital femoral deficiency is a Syme or Boyd amputation when the child begins to walk. A knee fusion is done when the child is older, and the patient functions as an above-the-knee amputee. Rotationplasty has been described as an alternative treatment that allows the patient to function as a below-the-knee amputee. None of the currently described types of rotationplasty address the problem of the unstable hip. METHODS: Three patients with severe congenital femoral deficiency underwent a unique single-stage reconstruction. In this procedure, the limb is completely detached except for the sciatic nerve and the femoral vessels. The proximal part of the dysplastic femur and some muscles are resected. The residual limb is externally rotated 180 degrees and the rotated distal part of the femur is fused to the pelvis. All of the muscles distal to the knee remain undisturbed. RESULTS: The anatomical knee in its rotated position functioned as a hip with flexion and extension, and the femoropelvic arthrodesis provided a more stable support. The rotated ankle acted as a knee, and the patients functioned as below-the-knee amputees. The duration of follow-up of these three patients was eight, six, and four years. Active hip flexion was 10 degrees to 70 degrees , 10 degrees to 90 degrees , and 0 degrees to 80 degrees , and active knee flexion was 900 and 95 . The patients' gait continued to improve as they matured. CONCLUSIONS: The femoropelvic arthrodesis provides a stable hip. Since the muscles distal to the knee are not disturbed, the problem of derotation of the limb, which is often seen following the Van Nes rotationplasty, is not seen after this operation. PMID- 11205863 TI - Primary repair of intraoperative disruption of the medical collateral ligament during total knee arthroplasty. AB - BACKGROUND: Intraoperative disruption of the medial collateral ligament during total knee arthroplasty is an uncommon complication that is frequently treated by implanting a prosthesis with varus-valgus constraint. To our knowledge, no data have been published on primary repair or reattachment of the medial collateral ligament and implantation of a minimally constrained posterior-stabilized or cruciate-retaining prosthesis. This retrospective study evaluates the hypothesis that satisfactory clinical results, at a minimum of two years, can be achieved with immediate repair or reattachment of the medial collateral ligament and without a constrained total knee prosthesis. METHODS: Of 600 knees treated with primary total knee arthroplasty, sixteen (in fourteen patients) sustained either a midsubstance disruption of the medial collateral ligament or an avulsion of the ligament from bone during the procedure. Preoperatively, all patients had either neutral or varus alignment and an intact medial collateral ligament. Midsubstance tears were treated with direct primary repair, and avulsions of the ligament off the tibia or femur were treated with suture-anchor reattachment to bone. All patients wore a hinged knee brace, with no limit to the range of motion, for six weeks postoperatively. Clinical and radiographic data were gathered prospectively as part of a database that was ongoing throughout the period of study; the cohort of patients was assembled retrospectively by searching that database. RESULTS: No patients were lost to follow-up. The mean duration of follow-up was forty-five months (range, twenty-four to ninety-five months). The Hospital for Special Surgery knee scores increased from a mean of 47 points (poor) preoperatively to a mean of 93 points (excellent) at the time of final follow-up. On physical examination, no patient had a Hospital for Special Surgery score in the fair or poor range and all patients had regained normal stability in the coronal plane both at full extension and at 30 degrees of flexion. No patient required knee bracing beyond the initial six-week postoperative period. The range of motion at the time of final follow-up averaged 108 degrees (range, 85 degrees to 125 degrees ), although one knee required manipulation under anesthesia to obtain a satisfactory range of motion. No arthroplasties required revision. Radiographic examination demonstrated appropriate limb alignment in all patients at the time of final follow-up. CONCLUSIONS: Intraoperative disruption of the medial collateral ligament can be treated with primary repair or reattachment of the ligament to bone and postoperative bracing with good results; this avoids the potential disadvantages associated with the use of varus-valgus constrained implants. PMID- 11205864 TI - Effects of radial head excision and distal radial shortening on load-sharing in cadaver forearms. AB - BACKGROUND: The present study was performed to measure changes in radioulnar load sharing in the cadaveric forearm following two orthopaedic surgical procedures that often have varying results: radial head excision and distal radial shortening. A better understanding of the biomechanical consequences of those procedures could aid surgeons in obtaining a more satisfactory clinical outcome. METHODS: Miniature load-cells were inserted into the proximal part of the radius and the distal part of the ulna in twenty fresh-frozen cadaveric forearms. Load cell forces, radial head displacement relative to the capitellum, and local tension within the central band of the interosseous membrane were measured simultaneously as the wrist was loaded to 133.5 N in neutral pronation-supination and neutral radioulnar deviation. Testing was repeated after incremental distal radial shortening and after removal of the radial head. RESULTS: With the elbow flexed to 90 degrees and in valgus alignment (the radial head in contact with the capitellum), the mean force in the distal part of the ulna was 7.1% of the applied wrist force and the mean force in the interosseous membrane was 4.0%. With the elbow in varus alignment (a mean initial gap of 1.97 mm between the radial head and the capitellum), the respective mean values were 27.9% and 51.2%. After excision of the radial head, the mean force in the distal part of the ulna increased to 42.4% of the applied wrist force and the mean force in the interosseous membrane increased to 58.8%, in both varus and valgus elbow alignment. The mean distal ulnar force increased with progressive distal radial shortening in both varus and valgus elbow alignment; after 6 mm of radial shortening, the distal ulnar force averaged 92.4% (in varus alignment) and 60.9% (in valgus alignment). Equal distal load-sharing between the radius and ulna occurred after approximately 5 mm of radial shortening with the elbow in valgus alignment and after approximately 2 mm of radial shortening with the elbow in varus alignment. In valgus alignment, the force in the interosseous membrane was negligible after all degrees of radial shortening; in varus alignment, the mean force in the interosseous membrane decreased from 51.2% (0 mm of distal radial shortening) to 0% (6 mm of distal radial shortening) because of progressive slackening of the interosseous membrane. CONCLUSIONS: Radial head excision shifted the applied wrist force that normally would be transmitted to the elbow, through radial head-capitellar contact, to the interosseous membrane. The resulting proximal radial displacement created an ulnar-positive wrist and increased distal ulnar loading. Radial shortening and ulnar lengthening procedures have been designed to shift the applied wrist force from the distal part of the radius to the distal part of the ulna; it is commonly assumed that these procedures have equivalent biomechanical effects. We found that radial shortening resulted in slackening of the interosseous membrane, thereby negating its ability to transmit load through the forearm. Slackening of the interosseous membrane would not be expected with distal ulnar lengthening procedures. CLINICAL RELEVANCE: When the radial head has been fractured or excised, the mechanical status of the interosseous membrane is critical to the load-sharing process. If the interosseous membrane remains intact, distal ulnar loads will be limited to less than half of the applied wrist force; if the interosseous membrane has been damaged, nearly the entire applied wrist force will be shifted to the ulna. The amount of radial shortening or ulnar lengthening performed at the time of surgery during joint-leveling procedures has been largely empirical. We found that distal ulnar load increased by approximately 10% for each millimeter of radial shortening. PMID- 11205865 TI - Expression of intercellular adhesion molecule-1 induced by high glucose concentrations in human aortic endothelial cells. AB - We examined the effects of high glucose concentrations on the expression of adhesion molecules in human aortic endothelial cells. Expression levels of both mRNA and protein of intercellular adhesion molecule-1 (ICAM-1) were increased after incubation of endothelial cells with 30 mM glucose for 24 h. The effect of glucose on ICAM-1 was concentration dependent, partially attributable to osmolarity, and enhanced by glycated-collagen. Staurosporine (10 nM), epalrestat (10 microM) suppressed the expression of ICAM-1 mRNA and protein induced by high glucose to variable extents. Aminoguanidine (50 mM) suppressed the expression of ICAM-1 protein. It is thought that soluble ICAM-1 protein is produced by shedding in human aortic endothelial cells because RNA for the soluble form of ICAM-1 formed by variant splicing has not been detected. These results show that glucose is an important determinant of ICAM-1 expression in endothelial cells, and suggest that ICAM-1 molecules induced by hyperglycemia may contribute to the development of atherosclerosis in diabetes mellitus. PMID- 11205866 TI - Panaxagin, a new protein from Chinese ginseng possesses anti-fungal, anti-viral, translation-inhibiting and ribonuclease activities. AB - From the roots of the Chinese ginseng Panax ginseng a protein designated panaxagin with ribonuclease activity, but possessing a sequence distinct from ribonucleases previously reported from ginseng calluses, was isolated. The purification protocol employed comprised extraction with cold saline, (NH4)2SO4 precipitation, ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on SP-Sepharose, and gel filtration on Superdex 75 by fast protein liquid chromatography. The purified protein was composed of two identical subunits each with a molecular weight of 26 kDa. Its N-terminal amino acid sequence exhibits sites of similarity with the sequences of plant ribosome inactivating proteins and fungal ribonucleases. The spectrum of biological activities of panaxagin encompassed ribonuclease activity toward yeast transfer RNA, translation-inhibitory activity in a rabbit reticulocyte lysate system, and antifungal activity against fungi including Coprinus comatus and Fusarium oxysporum, but not against Rhizoctonia solani. In addition it displayed an inhibitory activity against human immunodeficiency virus reverse transcriptase and succinylation augmented this activity. PMID- 11205867 TI - Chalcones are potent inhibitors of aromatase and 17beta-hydroxysteroid dehydrogenase activities. AB - Chalcones were tested for estimating anti-aromatase, anti-3beta-hydroxysteroid dehydrogenase delta5/delta4 isomerase (3beta-HSD) and anti-17beta-hydroxysteroid dehydrogenase (17beta-HSD) activities in human placental microsomes. In the present study, we have demonstrated for the first time that chalcones are potent inhibitors of aromatase and 17beta-hydroxysteroid dehydrogenase activities: these enzymes being considered as important targets in the metabolic pathways of human mammary hormone-dependent cells. Our results showed that naringenin chalcone and 4-hydroxychalcone were the most effective aromatase and 17beta-hydroxysteroid dehydrogenase inhibitors with IC50 values of 2.6 and 16 microM respectively. In addition, inhibitory effects of some flavones and flavanones were compared to those of the corresponding chalcones. A structure-activity relationship was established and regions or/and substituents essential for these inhibitory activities were determined. PMID- 11205868 TI - Optimization of the technique to isolate fetal hepatocytes, and assessment of their functionality by transplantation. AB - In contrast to adult hepatocytes, fetal hepatocytes (FH) are thought to be highly proliferative less immunogenic and more resistant to both cryopreservation and ischemic injury. In the present study, we describe the method for isolation of FH and the relationship between the transplantability of FH into the spleen of analbuminemic rats and expression of albumin mRNA. Rat FH were obtained using the nonperfusion collagenase/DNase digestion method. Nagase analbuminemic rats (NAR), a strain which bears a mutation that determines the impossibility of the normal splicing of the albumin mRNA were used as recipients. The transplanted FH immediately migrated to the liver via portal vein, and anchored there. To assess the functional state of the transplanted cells, one month after transplantation, the expression of the albumin gene was studied in the liver of the recipients. PMID- 11205869 TI - Isolation and characterization of a new ribosome inactivating protein, momorgrosvin, from seeds of the monk's fruit Momordica grosvenorii. AB - Momorgrosvin, a single-chained glycoprotein with a molecular weight of 27.7 kilodaltons and an isoelectric point of about 9 was isolated from the seeds of Momordica grosvenorii (Family Cucurbitaceae). The isolation procedure entailed acetone precipitation, affinity chromatography on Hi Trap Blue, cation exchange chromatography on Resource S and size exclusion chromatography on Superose 12. The sequence of the first eighteen N-terminal amino acid residues of momorgrosvin exhibited homology to those of RIPs from other Momordica species. Momorgrosvin inhibited protein synthesis in the rabbit reticulocyte lysate system with an IC50 of 0.3 nM and displayed RNA N-glycosidase activity giving rise to the diagnostic Endo's band at a concentration as low as 9 nM. The protein acted on tRNA to produce acid-soluble uv-absorbing species. PMID- 11205870 TI - Dipeptidyl peptidase IV is a target for covalent adduct formation with the acyl glucuronide metabolite of the anti-inflammatory drug zomepirac. AB - The nonsteroidal anti-inflammatory drug zomepirac (ZP) is metabolised to a chemically reactive acyl glucuronide conjugate (ZAG) which can form covalent adducts with proteins. In vivo, such adducts could initiate immune or toxic responses. In rats given ZP, the major band detected in liver homogenates by immunoblotting with a polyclonal ZP antiserum was at 110 kDa. This adduct was identified as ZP-modified dipeptidyl peptidase IV (DPP IV) by immunoblotting using the polyclonal ZP antiserum and monoclonal DPP IV antibodies OX-61 and 236.3. In vitro, ZAG, but not ZP itself, covalently modified recombinant human and rat DPP IV. Both monoclonal antibodies recognized DPP IV in livers from ZP- and vehicle-dosed rats. Confirmation that the 110 kDa bands which were immunoreactive with the ZP and DPP IV antibodies represented the same molecule was obtained from a rat liver extract reciprocally immunodepleted of antigens reactive with these two antibodies. Furthermore, immunoprecipitations with OX-61 antibody followed by immunolotting with ZP antiserum, and the reciprocal experiment, showed that both these antibodies recognised the same 110 kDa molecule in extracts of ZP-dosed rat liver. The results verify that DPP IV is one of the protein targets for covalent modification during hepatic transport and biliary excretion of ZAG in rats. PMID- 11205871 TI - Matrix metalloproteinase expression in cardiac myocytes following myocardial infarction in the rabbit. AB - Myocardial infarction (MI), leads to cardiac remodeling, thinning of the ventricle wall, ventricular dilation, and heart failure, and is a leading cause of death. Interactions between the contractile elements of the cardiac myocytes and the extracellular matrix (ECM) help maintain myocyte alignment required for the structural and functional integrity of the heart. Following MI, reorganization of the ECM and the myocytes occurs, contributing to loss of heart function. In certain pathological circumstances, the ECM is modulated such that the structure of the tissue becomes damaged. The matrix metalloproteinases (MMPs) are a family of enzymes that degrade molecules of the ECM. The present experiments were performed to define the time-course, isozyme subtypes, and cellular source of increased MMP expression that occurs following MI in an experimental rabbit model. Heart tissue samples from infarcted and sham animals were analyzed over a time-course of 1-14 days. By zymography, it was demonstrated that, unlike the sham controls, MMP-9 expression was induced within 24 hours following MI. MMP-3 expression, also absent in sham controls, was induced 2 days after MI. MMP-2 expression was detected in both the sham and infarcted samples and was modestly up-regulated following MI. Tissue inhibitor of metalloproteinase 1 (TIMP-1) expression was evaluated and shown to be down-regulated following MI, inverse of MMP-9 and MMP-3 expression. Further, MMP-9 and MMP-3 expression was detected by immunohistochemistry in myocytes within the infarct. Additional studies were conducted in which cultured rat cardiac myocytes were exposed to a hypoxic environment (2% O2) for 24 hours and the media analyzed for MMP expression. MMP-9 and MMP-3 were induced following exposure to hypoxia. It is speculated that the net increase in proteolytic activity by myocytes is a contributing factor leading to myocyte misalignment and slippage. Additional studies with a MMP inhibitor would elucidate this hypothesis. PMID- 11205872 TI - Involvement of apoptosis during deciduomal regression in pseudopregnant hamsters effect of progesterone. AB - We determined whether fragmentation of genomic DNA, apoptosis, occurs during deciduomal regression in pseudopregnant hamsters and the effect of progesterone on the apoptotic processes. Artificially induced deciduoma were obtained on different days of pseudopregnancy and separated into mesometrial and antimesometrial tissues. The deciduomal cell cycle progression and population profiles of both sides were compared by flow cytometry. The proportion of sub-G1 peak, which was correlated with the apoptotic cells, were about 10% on day 8 and reached to 40% in both tissues on day 10. Exogenous progesterone treatment by daily injection (2 mg; s.c.) on and after day 8 reduced the percentage of low molecular weight DNA in both tissues on day 10 and day 12 as compared to the nontreated control one, respectively. The appearance of DNA ladder was also delayed at least 24 h by progesterone administration. The intensity of DNA fragmentation was more pronounced in antimesometrial deciduoma. In situ 3'-end labeling of apoptotic cells further substantiated the apoptotic process. The apoptotic cells first appeared in the luminal region in antimesometrial deciduoma on day 8 and spreaded all over the entire deciduomal tissue on day 10. Progesterone treatment stimulated deciduomal proliferating cell nuclear antigen (PCNA) expression, maintained deciduoma until day 14 and retarded the differentiation and regeneration of the uterine epithelium. PMID- 11205873 TI - Changes in expression of ion channels and aquaporins mRNA during differentiation in normal human nasal epithelial cells. AB - Integrity of the airway epithelium is important for pulmonary defense mechanisms to infection. The lining of the airway contains a diverse population of cell types. Understanding about progenitor-progeny relationships during renewal of airway epithelium is important for elucidating mechanisms of injury repair or oncogenesis. Primary culture of airway epithelia is a good model for studying differentiation process of epithelial cells. Ion channels and aquaporins(AQPs) play a critical role on ion and fluid transport across airway epithelia. However, changes in their expression during differentiation of airway epithelial cells have not been reported yet. This study was undertaken to identify isoforms of aquaporins in cultured normal human nasal epithelial cells (NHNE) and effects of various culture conditions on expression of differentiation markers and channels. 1. Degenerative RT-PCR revealed that AQP3 and AQP4 are expressed in cultured NHNE cells. 2. Culture of NHNE cells on permeable filters induced expression of mucin, aquaporins and CFTR. 3. Retinoic acid induced morphological changes in NHNE cells and inhibited their proliferation. The treatment of retinoic acid induced expression of mucin and CFTR, whereas it inhibited expression of cornifin. The effect of retinoic acid was enhanced by culture of cells on permeable filters. 4. Dexamethasone induced ENaC expression in NHNE cells grown on permeable supports only, but did not affect expression of mucin, aquaporins and CFTR. These results indicate that cultured NHNE cells express aquaporins (AQP3 and 4), CFTR and ENaC, and culture of NHNE cells on permeable filters induces differentiation in to mucosecretory and surface epithelial cells, and that effects of retinoic acid and dexamethasone on gene expression are affected by culture conditions. PMID- 11205874 TI - Tetrandrine inhibits Ca2+ release-activated Ca2+ channels in vascular endothelial cells. AB - The effects of tetrandrine (TET), a Ca2+ antagonist of bis-benzylisoquinoline alkaloid origin, on cultured single bovine pulmonary artery endothelial cells were examined using fluorescence ratio imaging and whole-cell attached patch clamp techniques. Thapsigargin (TSG, 100 nM), a selective endoplasmic reticulum Ca2+-ATPase pump inhibitor known to induce the release of nitric oxide (NO) from vascular endothelial cells via a Ca2+-dependent manner, caused a rapid elevation of cytosolic Ca2+ concentration, which was inhibited by 30 microM TET. In whole cell patch-clamp study using the same vascular endothelial cells, addition of 100 nM TSG caused a significant enhancement of depolarization-evoked Ca2+-dependent, outward K+ currents, which could also be abolished by 30 microM TET. The present results demonstrate directly that TET, in addition to its known inhibitory effects on vascular smooth muscle by virtue of its Ca2+ antagonistic actions, also inhibits NO production by the endothelial cells through blockade of Ca2+ release-activated Ca2+ channels. PMID- 11205875 TI - Roles of Se and NO in apoptosis of hepatoma cells. AB - Mice inoculated with hepatoma cell (H22) suspension subcutaneously at their right axilla were administered orally with kappa-selenocarrageenan (Se) solution, the inoculated hepatoma's growth was suppressed. Different concentrations of Se solution added in human hepatoma cell line culture could inhibit proliferation and induce apoptosis in hepatoma cells. Meanwhile Se solution could increase the activity of glutathione peroxidase (GSH-Px) in the mice's plasma and the content of NO in the mice's sera and the hepatoma cell culture supernatant as well. Therefore, apoptosis in hepatoma cell induced by Se solution may be associated with the increase in antioxidative activity, the suppression free radical's intervention, and the excessive release of NO by stress. PMID- 11205876 TI - Pavlovian conditioning of lung anaphylactic response in rats. AB - The present experiment was undertaken to verify if it is possible to impose Pavlovian conditioning on a lung anaphylactic response (LAR) in rats. Two experiments were done. In the 1st, egg albumin (OVA) aerosol inhalation, which induces signs and symptoms of LAR in OVA- sensitized rats, was paired with an audiovisual cue (conditional stimulus, CS). After reexposure to the CS, the signs and symptoms of LAR were quantitatively measured using a scoring system specially developed for this evaluation; the levels of stress response and anxiety were also quantified. Results showed that the rats reexposed to CS only, displayed LAR scores not significantly different from those reexposed to both CS and the antigen; animals of these groups showed significantly higher LAR scores than rats that received no OVA aerosol challenge. High levels of stress and anxiety were observed 30-40 min after the challenge with OVA aerosol. In the 2nd experiment, rats sensitized with OVA and submitted or not to Pavlovian conditioning were observed in the open-field and in the plus maze apparatus in the absence of OVA aerosol but in the presence of the CS; after behavioral observations the animals were sacrificed for serum corticosterone level determination. Both behavioral and biochemical data showed high levels of stress and anxiety in rats for which the antigen was previously paired with the CS; these changes were not observed in animals which received the antigen 24 h after the presentation of the CS (unpaired) or in those exposed to PBS aerosol (the OVA vehicle) only. The present data show not only that LAR can be submitted to Pavlovian conditioning, but also and importantly, that high levels of stress and anxiety are related to the course of LAR. PMID- 11205877 TI - Insulin restores neuronal nitric oxide synthase expression in streptozotocin induced diabetic rats. AB - Nitric oxide (NO) is known to play an important role in the pathophysiology of insulin-dependent diabetic mellitus (IDDM). In an attempt to investigate the relation between insulin and NO in IDDM, the present study employed male Wistar rats to induce IDDM by intravenous injection of streptozotocin (STZ). Four groups of rats were used; untreated normal control group, insulin treated STZ group, vehicle-treated STZ control, and one group of age-matched rats which were orally supplied with glucose to increase plasma glucose (glucose-challenged rats). Changes of the activity and gene expression of neuronal nitric oxide synthase (nNOS) were examined in cerebellum and kidney of these groups. The activity of nNOS in cerebellum, determined by conversion of [3H] L-arginine to [3H] L citrulline, in STZ-induced diabetic rats was markedly lower than normal rats. Insulin treatment reversed the nNOS activity. Similar reversion by insulin treatment was also obtained in the gene expression of nNOS. However, the activity and gene expression of nNOS in glucose-challenged rats were not different from those in normal rats. The role of hyperglycemia can thus be ruled out. These findings indicated that an impairment of nNOS in the brain of rats with IDDM is mainly due to the absence of insulin. PMID- 11205878 TI - Effect of endothelin-1(1-31) on p38 mitogen-activated protein kinase in cultured human mesangial cells. AB - It was reported that human chymase cleaves big endothelins (ETs) at the Tyr31 Gly32 bond and produces 31-amino acid ETs(1-31). In this study, we investigated the effect of ET-1(1-31) on p38 mitogen-activated protein kinase (p38-MAPK) activity in human mesangial cells (HMCs). By measuring the kinase activity, we demonstrated that ET-1 (1-31) activated the p38-MAPK dose-dependently (10(-9) M to 10(-7) M), which was inhibited by SB203580. The p38-MAPK activation induced by ET-1(1-31) peaked at 10 minutes. BQ123 almost abolished ET-1(1-31)-induced p38 MAPK activation, whereas BQ788 failed to inhibit it. These findings suggest that the stimulatory effect of ET-1(1-31) on p38-MAPK activation is mediated through ET(A) or ET(A)-like receptor. In conclusion, ET-1(1-31) induced increase in p38 MAPK activation in cultured HMCs. PMID- 11205879 TI - Timing is everything the role of kinetics in G protein activation. AB - The binding of a drug to a G-protein coupled receptor initiates a complex series of dynamic events that ultimately leads to a cellular response. In addition to the concentrations of receptor, drug and G-protein, important determinants of the cellular response are the rates at which these species interact. However, most models for G-protein coupled receptor signaling are equilibrium models that neglect the role of reaction kinetics. A kinetic ternary-complex model of signaling through G-protein coupled receptors is presented. We demonstrate that this kinetic model can make significantly different predictions than an equilibrium ternary complex model, which provides a different perspective on multiple aspects of the signal transduction cascade, such as agonist efficacy, the effect of precoupled receptors, and the role of RGS proteins. Incorporation of the reaction kinetics is critical for a complete understanding of signal transduction and will ultimately impact the fields of drug discovery and drug design. PMID- 11205881 TI - Chronic pharmacological treatment with certain antidepressants alters the expression and DNA-binding activity of transcription factor AP-2. AB - Several of the genes in the serotonergic and the dopaminergic systems have consensus binding sites for the AP-2 transcription factor family in their regulatory regions. Imbalances in these systems have been implicated in many psychiatric disorders, including depression and bipolar affective disorder. We have made an effort to further elucidate the molecular mechanisms of drugs used for affective disorders. Recently, we analyzed the effects of chronic treatment with certain antidepressants on AP-2 in rat brain. The present study demonstrates that chronic administration of three different classes of antidepressants modulates the DNA-binding activity of AP-2 in the rat brain. Chronic administration of citalopram (10 mg/kg), imipramin (10 mg/kg) and lithium chloride (40 mg/kg) significantly decreased DNA-binding activity of AP-2. Furthermore, citalopram (10 mg/kg) and imipramin (10 mg/kg) significantly decreased the amount of AP-2alpha protein as determined by ELISA. In addition, citalopram (10 mg/kg) significantly decreased the amount of AP-2beta protein. In contrast, chronic administration of lithium-chloride (40 mg/kg) did not affect the amount of the two AP-2 isoforms. An increased understanding of the function of transcription factors and their involvement in human disease, such as depression, could make it possible in the future to selectively modulate relevant target genes directly. PMID- 11205880 TI - Hyperpolarization contributes to vascular hyporeactivity in rats with lipopolysaccharide-induced endotoxic shock. AB - We have examined the role of membrane hyperpolarization in mediating vascular hyporeactivity induced by bacterial lipopolysaccharide (LPS) in endothelial denuded strips of rat thoracic aorta ex vivo. The injection of rats with LPS caused a significant fall of blood pressure and a severe vascular hyporeactivity to norepinephrine. The membrane potential recording showed that endotoxemia caused a hyperpolarization when compared to the control. This hyperpolarization was fully restored by methylene blue (MB; 10 microM) and partially reversed by Nomega-nitro-L-arginine methyl ester (L-NAME; 0.3 mM), 1H-[1,2,4]oxadiazolo[4,3 a]quinoxalin-1-one (ODQ; 1 microM), tetraethylammonium (TEA; 10 mM), charybdotoxin (CTX; 0.1 microM), or glibenclamide (GB; 10 microM), however, this hyperpolarization was not significantly affected by apamin (0.1 microM), 4 aminopyridine (4-AP; 1 mM), or Ba2+ (50 microM). In addition, the basal tension of the tissues obtained from endotoxemic rats was enhanced by the following order: MB > or = ODQ > TEA > or = L-NAME > or = CTX > GB; whereas apamin, 4-AP or Ba2+ had no significant effects on these tissues. In contrast, none of these inhibitors had significant effects on the membrane potential or the basal tension in control tissues. Our electrophysiological results further confirmed previous studies showing that in addition to nitric oxide, the large conductance Ca2+ activated K+-channels and ATP-sensitive K+-channels are, most likely, responsible for endotoxin-mediated hyporeactivity to vasoconstrictor agents in vascular smooth muscle. PMID- 11205882 TI - Hydrogen peroxide downregulates human organic anion transporters in the basolateral membrane of the proximal tubule. AB - Hydrogen peroxide (H2O2) is known to be involved in drug-induced and ischemic proximal tubular damage. The purpose of this study was to elucidate the effects of hydrogen peroxide on organic anion transport mediated by human organic anion transporters 1 and 3 (hOAT1 and hOAT3), which are localized at the basolateral side of the proximal tubule. For this purpose, we established and utilized the second segment of the proximal tubule cells from mice stably expressing hOAT1 or hOAT3 (S2 hOAT1 or S2hOAT3, respectively). H2O2 induced a dose- and a time dependent decrease in organic anion transport mediated by hOAT1 and hOAT3. Kinetic analysis revealed that H2O2 decreased the Vmax, but not Km of organic anion transport both in S2hOAT1 and S2hOAT3. The effects of gentamicin, known to induce proximal tubular damage via the production of H2O2, on the organic anion transporters were also examined. Gentamicin induced a significant decrease in organic anion transport in S2hOAT1 but not S2hOAT3. H2O2-induced decrease in organic anion transport was significantly inhibited by pretreatment with pyruvate as well as catalase, whereas the gentamicin-induced decrease was significantly inhibited by pretreatment with pyruvate but not with catalase. In conclusion, these results suggest that H2O2, which is produced during tubular injuries, downregulates organic anion transport mediated by both hOAT1 and hOAT3, leading to further modulation of pathophysiology. PMID- 11205883 TI - Protective effect of histidine on potassium chloride depolarization enhances 1 methyl-4-phenylpyridinium ion-induced hydroxyl radical generation in the rat striatum. AB - The present study examined the antioxidant effect of histidine on extracellular potassium ion concentration, [K+]o-induced depolarization enhances 1-methyl-4 phenylpyridinium ion (MPP+)-induced hydroxyl radical (*OH) generation in the rat striatum. Rats were anesthetized and sodium salicylate in Ringer's solution (0.5 nmol/M microl/min) was infused through a microdialysis probe to detect the generation of *OH as reflected by the nonenzymatic formation of 2,3 dihydroxybenzoic acid (DHBA) in the striatum. Induction of [K+]o (20, 70 and 140 mM) significantly increased the level of 2,3-DHBA by the action of MPP+ (5 mM) in a concentration-dependent manner. However, histidine (25 mM) reduced the [K+]o induced *OH formation. Although the level of MPP+-induced dopamine (DA) and 2,3 DHBA formation after [K+]o (70 mM) treatment increased, [K+]o failed to increase either the level of MPP+-induced DA and 2,3-DHBA in the reserpinized group. When iron (II) was administered to [K+]o (70 mM)-pretreated rats, iron (II) clearly produced a dose-dependent increase in the level of 2,3-DHBA, as compared with MPP+-only treated rats. However, in the presence of histidine (25 mM), the effect of [K+]o was abolished. These results indicated that histidine may reduce the [K+]o-induced depolarization enhanced *OH formation by the action of MPP+ in the rat striatum. PMID- 11205884 TI - Troglitazone stimulates acetyl-CoA carboxylase activity through a post translational mechanism. AB - Troglitazone, a thiazolidinedione, is known to act as an insulin sensitizer. The various effects of the drug include stimulation of glucose utilization and inhibition of gluconeogenesis and fatty acid oxidation. We studied the effect of troglitazone treatment on rat liver acetyl-CoA carboxylase (ACC), the key enzyme that catalyzes the formation of malonyl-CoA, the rate-limiting step in the synthesis of long chain fatty acids. Treatment of rats with troglitazone for 18 days resulted in more than 200% increase in the activity of hepatic acetyl-CoA carboxylase (1.01+/-0.14 and 2.33+/-0.28 mU/mg supernatant protein for control and troglitazone-treated rats, respectively) (p<0.001). The expression of acetyl CoA carboxylase mRNA, as studied by RNAse protection assay, was not significantly different between the two groups of animals. The ACC from control and troglitazone-treated groups was purified by avidin-affinity chromatography. The purified enzyme migrated as a major protein band (Mr 262,000) on SDS polyacrylamide gels. Troglitazone treatment was associated with increased citrate sensitivity of ACC. The specific activity of the purified preparation in troglitazone-treated rats was increased by 67% (2.5 vs. 1.5 U/mg). Quantitation of alkali-labile phosphate content of the purified preparation revealed 5.66+/ 0.17 and 6.29+/-0.13 mol Pi/mol subunit of 262 Kda for control and troglitazone treated rats, respectively (P<0.01). The subtle increase in phosphate content does not explain the observed activation of the enzyme. It is possible that additional mechanisms such as troglitazone related rearrangement of the occupancy of select phosphate binding sites or altered binding of the biotin cofactor may also contribute to the observed activation of ACC. PMID- 11205885 TI - Pharmacological profile of nitrergic nerve-, nitric oxide-, nitrosoglutathione- and hydroxylamine-induced relaxations of the rat duodenum. AB - Activation of inhibitory nonadrenergic noncholinergic (NANC) nerves in the rat duodenum cause relaxations, which are reduced by nitric oxide synthase (NOS) inhibitors indicating that this response involves a nitrergic neurotransmission. The precise nature of the nitrergic neurotransmitter is still controversial since nitric oxide (NO) scavengers and superoxide generators, even in the presence of superoxide dismutase inhibitors, failed to inhibit nitrergic neurotransmission mediated relaxations. In order to understand the role of NOS in nitrergic neurotransmission and considering that N-OH-arginine (OH-L-Arg), L-citrulline, NO, S-nitrosoglutathione (GSNO) and hydroxylamine (NH2OH) can be formed in cells during the N(G)-oxidation of L-arginine catalyzed by NOS we explored whether any of these products could exhibit biological properties comparable to those of the nitrergic neurotransmitter. After establishing which of them was able to relax the rat duodenum, the pharmacological profile of such effect was determined employing oxyhemoglobin (OxyHb), pyrogallol (PYR), hydroquinone (HQ), hydroxocobalamin (HC) or carboxy-PTIO (C-PTIO) and compared with that of nerve mediated relaxations. NO, GSNO and NH2OH, but not OH-L-ARG and L-citrulline, caused concentration-dependent relaxations that were not affected by tetrodotoxin or L-NOARG. OxyHb almost abolished NO-induced relaxations but decreased only marginally the magnitude of nerve-, NH2OH- and SNG-induced relaxations. PYR, HQ and C-PTIO reduced significantly GSNO- and NO- induced relaxations but did not affect those induced by NH2OH or nerve activation. In contrast, HC abolished NO induced relaxations while it did not affect those induced by GSNO, NH2OH and nerve activation. The catalase inhibitor 1,2,4 aminotriazole failed to affect nerve and NH2OH induced relaxations. These findings indicate that among the products that can be formed during NOS catalyzed L-arginine N(G)-oxidation, only NH2OH caused relaxations that exhibited a pharmacological profile similar to those induced by the nitrergic neurotransmitter. Furthermore, if NH2OH is the actual neurotransmitter it appears to be acting either directly or by a catalase independent release of NO. PMID- 11205886 TI - Modulation of NMDA- and (+)TAN-67-induced nociception by GABA(B) receptors in the mouse spinal cord. AB - The present study was designed to investigate the effect of a selective GABA(B) receptor agonist baclofen on the pain-like nociceptive behavior (scratching, biting and licking) induced by intrathecal (i.t.) injection of N-methyl-D aspartate (NMDA) or (+)TAN-67, the enantiomorphs of 2-methyl-4aalpha-(3 hydroxyphenyl)-1,2,3,4,4a,5,12,12aalpha-octahydro-quinolino[2,3,3g]isoquinoline (TAN-67), in the mouse. NMDA (0.05-0.2 microg/mouse) given i.t. immediately caused nociception in a dose-dependent manner. The nociception was significantly antagonized by i.t. co-injection with dizocilipine (0.1-1.0 microg/mouse), a non competitive NMDA receptor antagonist. I.t. co-injection with baclofen (37.5-150 ng/mouse) significantly reduced the NMDA-induced nociceptive behavior in a dose dependent fashion. The inhibition produced by baclofen was completely reversed by a selective GABA(B) receptor antagonist 2-hydroxysaclofen (0.15 and 0.3 microg/mouse). An i.t. injection of (+)TAN-67 at doses of 3.75-15 microg/mouse elicited a long-lasting and a dose-related nociception. The nociceptive behavior induced by (+)TAN-67 given i.t. was markedly suppressed by i.t. co-injection with baclofen (3-30 ng/mouse), and the inhibitory effect of baclofen was prevented by i.t. injection of 2-hydroxysaclofen (1 and 3 microg/ mouse). In addition, the (+)TAN-67-induced nociception was also attenuated by i.t. co-injection with dizocilipine (0.1-1.0 microg/mouse). These results suggest that spinal GABA(B) receptors may be implicated in the expression of nociception elicited by i.t. injection of either NMDA or (+)TAN-67 in the mouse. PMID- 11205887 TI - Tyrosine phosphorylation increases Ca2+ sensitivity of vascular smooth muscle contraction. AB - In order to elucidate the role of tyrosine phosphorylation in vasoconstriction, we investigated the effects of inhibitors of tyrosine kinase (genistein, 30 microM) and phosphatase (sodium o-vanadate, 5 microM) on the contraction of aorta isolated from guinea pig. Genistein significantly inhibited norepinephrine induced contraction, but it did not affect that induced by KCI. Thus, tyrosine phosphorylation may not be involved in the contractile response to KCI alone. The aortic contraction elicited by KCl was significantly augmented by sodium o vanadate, which increased both the maximum force and pD2 values of KCl contraction. In the presence of verapamil, KCl-induced contraction was abolished even after pretreatment with sodium o-vanadate. Sodium o-vanadate also augmented Ca2+-induced contraction in the aortic strips depolarized with KCl, increasing both its maximum force and pD2 values. Neither basal 45Ca2+ uptake nor verapamil sensitive 45Ca2+ uptake induced by KCl were affected by pretreatment with sodium o-vanadate. These results suggest that tyrosine phosphorylation is involved in the contraction of guinea-pig aorta not through transplasmalemmal Ca2+ entry but through increased Ca2+ sensitivity of the intracellular contractile pathway. PMID- 11205888 TI - Effects of sulfhydryl modification on adrenal nicotinic acetylcholine receptors: disulfide integrity is not essential for activation. AB - The importance of disulfide bridges in muscle nicotinic receptors is well established; however, for neuronal nicotinic receptors, the effects of sulfhydryl modification are less definitive. In these studies the effects of treatment with the mild reducing agent, dithiothreitol, on adrenal nicotinic receptors are described. We have found that following dithiothreitol treatment, adrenal chromaffin cells retained the ability to be stimulated by a variety of nicotinic receptor agonists including nicotine, acetylcholine, cytisine, epibatidine, and bromoacetylcholine. However, with dithiothreitol treatment, changes in apparent affinities were seen with two agonists, epibatidine and bromoacetylcholine. These effects of dithiothreitol on apparent affinities were concentration-dependent and reversible upon treatment with an oxidizing agent. Dithiothreitol treatment also produced effects on secretion that were independent of nicotinic receptor activation. Our results are unlike those in other tissues containing nicotinic receptors and suggest that subunit composition of nicotinic receptors influences the functional outcome of sulfhydryl modification. PMID- 11205889 TI - Evidence of prooxidant and antioxidant action of melatonin on human liver cell line HepG2. AB - The aim of this study was to evaluate melatonin cytotoxicity by measuring its effects on various cellular targets. Cell viability, intracellular reduced glutathione (GSH) level, and reactive oxygen species (ROS) production were assessed in the human liver cell line (HepG2), after incubation with increasing melatonin concentrations (0.1-10,000 microM). The incubation times tested were 24, 72, and 96 h for cell viability and intracellular GSH level, and 15 and 45 minutes for ROS production. Cellular target evaluations were possible in living cells by means of a new microplate cytofluorimeter. This technology was suitable for the assessment of cell viability, GSH level, and ROS overproduction with, respectively, neutral red, monochlorobimane (mBCl), and 2',7'-dichlorofluorescin diacetate (DCFH-DA) fluorescent probes. At the lowest melatonin concentrations (0.1-10 microM) and for a relatively short incubation time (24 h), the antioxidant effect of melatonin was revealed by an increased intracellular GSH level, associated to cell viability improvement. In contrast, after longer incubation (96 h), cell viability significantly decreased with these lowest melatonin concentrations (0.1-10 microM). Moreover, high melatonin concentrations (1,000-10,000 microM) induced GSH depletion. This oxidative stress is associated with ROS overproduction from 10 microM after only 15 minutes of incubation. This dual effect is strong evidence that, in vitro, melatonin can be both antioxidant and prooxidant on the human liver cell line, depending on the concentration and incubation time. PMID- 11205890 TI - Catcholamine and nitric oxide systems as targets of chronic lead exposure in inducing selective functional impairment. AB - Rats were exposed for ten months to 60 ppm of lead (Pb, as acetate) in drinking water to further assess cardiovascular effects of chronic Pb exposure. At the end of the treatment, mean blood Pb was 3.1+/-0.3 microg/dL in the control rats and 22.8+/-1.2 microg/dL in the Pb-exposed rats (means+/-SE, n=12 in each group); these values were not comparable to those of humans. Pb greatly increased plasma levels of noradrenaline (NA) and adrenaline (A), but not those of L-DOPA and dopamine; monoaminoxidase activity was augmented by Pb, mostly in the aorta and in the liver; the aorta, liver, heart and kidney showed discrete histopathological alterations in the Pb-exposed rats, in which plasma levels of nitric oxide (NO, determined as L-citrulline) were reduced. Pb was able to induce blood hypertension, resulting from increase of cardiac inotropism and, mostly, total peripheral resistance. These data were discussed also in relation to those obtained in our previous studies carried out in rats exposed to Pb in drinking water (15-60 ppm) for periods ranging from five to eighteen months. Pb appeared to increase both sympathetic nerve activity by central mechanisms (thus increasing plasma NA and A) and cyclic adenosine monophosphate (cAMP)-dependent availability of calcium ions (Ca++) for contractile mechanisms in the vascular and cardiac myocells (also through an increased vascular alpha2- and myocardial beta1-adrenoreceptor reactivity). The reduction of plasma NO, contributing to increase vascular resistance and cardiac inotropism, was explained as a result of actions of Pb on enzyme activities concerned with the kallikrein-kinin (KK) and renin-angiotensin-aldosterone (RAA) systems. It was concluded that chronic Pb exposure is able to affect selective neuroendocrine (i.e., catecholamine), au- tacoidal (i.e., KK and RAA) and transductional pathways (i.e., cAMP, NO, Ca++) involved in the cardiovascular function. PMID- 11205891 TI - Testosterone inhibits expression of inducible nitric oxide synthase in murine macrophages. AB - We investigated the effect of testosterone, the main sexual steroid hormone in men, upon inducible nitric oxide synthesis in murine macrophages. Incubation of murine macrophages (RAW 264.7 cells) stimulated by bacterial lipopolysaccharide (2 microg/ml) with increasing amounts of testosterone (0.1-40 microM) showed a dose dependent inhibition of inducible nitric oxide synthesis. Inducible nitric oxide synthase protein expression was reduced in a dose dependent manner as revealed by immunoblotting when cells were incubated with increasing amounts of testosterone. This was associated with a decline in iNOS mRNA-levels as determined by competitive semiquantitative PCR. As nitric oxide plays an important role in immune defense and atherosclerosis prevention, testosterone induced iNOS inhibition could lead to an elevated risk of infection as well as to the development of atherosclerotic lesions. PMID- 11205892 TI - Cocaine metabolism in human fetal and adult liver microsomes is related to cytochrome P450 3A expression. AB - Cocaine N-demethylation to norcocaine was studied in human liver microsomes of different ages. Norcocaine was formed at a considerable rate in fetal (45.4+/ 18.2 nmol/mg x hour, n = 8) and adult specimens (82.0+/-46.6 nmol/mg x hour, n = 15), p = 0.04 (Mann-Whitney). Furthermore, the apparent Km values in fetal specimens (0.57 and 0.48 mM, n = 2) showed a higher affinity compared with those of adults (mean value 2.7 (1.8-4.25) mM, n = 4). Estimated enzyme metabolic clearance with respect to P450 total content was higher in fetal than in adult liver microsomes (2.22 ml/nmol P450 x hour, and 0.18 (0.14-0.23) ml/nmol P450 x hour, respectively). Several drugs, known to be CYP3A substrates, were used as potential inhibitors of cocaine metabolism. Midazolam, ergotamine and erythromycin showed strong inhibition (approx. 70 %) when used at concentrations of 500 microM (midazolam, erythromycin) or 200 microM (ergotamine). The metabolism of 1 mM cocaine correlated strongly with immunodetected CYP3A protein determined by Western blotting in both fetal (r = 0.89, p = 0.19) and adult specimens (r = 0.82, p < 0.01) . These findings further support CYP3A as a major catalyst of norcocaine formation in human liver microsomes. These results are important given the potential risk of toxicity to the foetus of maternal cocaine abuse during pregnancy. Although the high Km values found in adult livers reduce the importance of this enzyme pathway in cocaine detoxication, this pathway would emerge as significant in circumstances of CYP3A induction and/or drug interactions leading to potential liver toxicity in chronic cocaine abusers. PMID- 11205893 TI - Desipramine induced changes in salivary proteins, cultivable oral microbiota and gingival health in aging female NIA Fischer 344 rats. AB - Cyclic antidepressants are still a dominating group of psychotherapeutic drugs used in the treatment of depression. One of their major side effect is salivary gland dysfunction (oral dryness, xerostomia), leading in humans to increased oral disease and dysfunction of speech, chewing, swallowing and taste. The purpose of this study was to assess the effects of the long-term administration of the tricyclic antidepressant desipramine and the reversibility of this treatment following a 15 d washout period on specific salivary proteins, composition of oral microbiota, and oral health (gingivitis) of aging female F344 rats. Total salivary proteins showed decreased concentrations with age and desipramine. Similar SDS/PAGE protein profiles appeared in all phases but in different relative amounts with age and treatment. While certain proteins maintained steady levels (lactoferrin) or decreased with age and treatment (amylase), the synthesis of proline-rich proteins, high molecular weight mucin-type glycoproteins, and lysozyme was induced with desipramine and age. The oral microbiota was significantly changed with age and the administration of the antidepressant. The incidence of gingivitis with desipramine was highest in the oldest animals, For the different parameters measured, recovery was delayed with age. These data indicate, that desipramine has profound effects on salivary protein secretion. This may partially explain the changes in microbiota and the increased incidence of gingivitis. PMID- 11205895 TI - Quantitative and qualitative gender-related differences in jejunal glutathione S transferase in the rat effect of testosterone administration. AB - Gender-related differences and the regulation by testosterone of glutathione S transferase were studied in rat jejunum. We analyzed enzyme activity and the relative content of GST subunits. Four experimental groups of adult rats were studied: normal males, castrated males, castrated males injected with testosterone and normal females. Glutathione S-transferase activity was assayed using 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene as substrates. Differences in subunit composition among groups were evaluated by western blot analysis. The results demonstrated that 1-chloro-2,4-dinitrobenzene conjugation rate is higher in normal males than in normal females and castrated males. Testosterone administration to castrated males raised the activity up to the level observed in normal males. No significant difference in glutathione S transferase activity towards 1,2-dichloro-4-nitrobenzene was observed among groups. Western blot analysis revealed that males and females differ in all subunits tested that is, rGSTA2, rGSTM1, rGSTM2 and rGSTP1, and that testosterone regulates the content of rGSTM1, rGSTM2 and rGSTP1. In conclusion, jejunal GST shows a gender-dependent regulation affecting both enzyme activity and subunit composition, and testosterone appears to be one of the factors involved. PMID- 11205894 TI - The continuous administration of aspirin attenuates atherosclerosis in apolipoprotein E-deficient mice. AB - Aspirin reduces the incidence of thrombotic occlusive events. Classically this has been thought to be due to the platelet inhibitory action of aspirin but it has recently been shown that inflammation plays a predominant role in the initiation and progression of lesions in atherosclerosis. In humans, treatment with aspirin reduces cardiovascular risk and slows carotid plaque growth in a dose-dependent fashion. We have explored this issue in Apo E-deficient mice on a high-fat, high cholesterol diet which provided these animals with a continuous administration of 500 microg/day of acetylsalicylic acid in the drinking water. After 10 weeks of treatment, the size of the atherosclerotic lesion at the aortic sinus had reduced by 35%. At the end of the trial there were no significant changes in either plasma lipids or in the quantitative distribution among lipoproteins. Likewise, the total antioxidant status and the resistance of plasma to oxidation in vitro was similar and there was no change in the distribution of iron deposits and in the relative composition of plasma pro-oxidants and antioxidants, or in the concentration of plasma in ferritin. Therefore, it is our hypothesis that the antiinflammatory effect is responsible for the reduction in lesion size. We propose that antiinflammatory molecules which do not cause gastrointestinal complications should be tested in humans to determine long-term efficacy in the attenuation of atherosclerosis. PMID- 11205896 TI - Mechanisms of [Ca2+]i elevation by H2O2 in islets of rats. AB - Activity of reactive oxygen species is elevated in diabetes mellitus and has been implicated in the destruction of cellular components. The toxic effect of reactive oxygen species was investigated by testing the effect of H2O2 on [Ca2+]i in isolated islets of Langehans. H2O2 increased [Ca2+]i in a dose-dependent manner, which was irreversible at high concentrations. The maximum effect of H2O2 on [Ca2+]i was larger than those of KCl, glucose, ATP, carbachol and endothelin 1. The effect of H2O2 was only partially attenuated by removal of external Ca2+ and by the in-organic Ca2+ channel blocker nickel, but was not blocked by voltage dependent or -independent Ca2+ channel blockers nimodipine, nicardipine, SK&F 96365, econazole and lanthanum. H2O2, disrupted [Ca2+]i homeostasis in islets by affecting both release and influx of Ca2+ and causing dysfunction of Ca2+ clearance systems and may contribute to the pathological process of diabetes. PMID- 11205897 TI - Nerve growth factor exerts differential effects on the growth of human pancreatic cancer cells. AB - Nerve growth factor (NGF) exerts both stimulatory and inhibitory effects on neuronal and certain nonneuronal tumors with the effect based on the type of tumor. We investigated NGF and its receptors (TrkA and p75) in pancreatic cancer cells (PANC-1, MIA-PaCa-2, CAPAN-1, ASPC-1, and T3M4) by reverse transcription PCR, Western blot analysis, NGF ELISA, and growth assays. NGF mRNA was present at comparable levels in all five pancreatic cancer cell lines. TrkA expression was relatively high in PANC-1 and MIA-PaCa-2 cells and low in CAPAN-1, ASPC-1, and T3M4 cells. p75 expression was high in PANC-1, MIA-PaCa-2, and T3M4 cells, moderate in CAPAN-1, and low in ASPC-1 cells. By ELISA assay, the intracellular NGF content in all cell lines was approximately 40 pg/10(6) cells. NGF content increased significantly in PANC-1 and MIA-PaCa-2 cells when these cells were cultured with serum-free media, whereas there was no change in the other cancer cell lines. PANC-1 and MIA-PaCa-2 cells but not the other cell lines released NGF in the culture media. Exogenous NGF stimulated the growth of PANC-1 and MIA-PaCa 2 cells, inhibited the growth of T3M4 and CAPAN-1 cells in a dose- and time dependent manner, and did not affect the growth of ASPC-1 cells. NGF led to the phosphorylation of TrkA, mitogen-activated protein kinase (MAPK), and p38 MAPK but not stress-activated protein kinase/c-Jun NH2-terminal kinase in PANC-1 and MIA-PaCa-2 cells. In contrast, in the other pancreatic cancer cell lines none of these kinases were phosphorylated by NGF. In conclusion, the effects of NGF on pancreatic cancer cell growth are dependent on the expression levels and the balance of its TrkA and p75 receptors. NGF-induced pancreatic cancer cell growth seems to be mediated through the phosphorylation of TrkA and subsequently via MAPK. These results point to a previously unknown autocrine/paracrine pathway in pancreatic cancer, suggesting that NGF-TrkA interactions are important factors influencing cell growth and spread in this malignancy. PMID- 11205898 TI - Novel tankyrase-related gene detected with meningioma-specific sera. AB - In many meningiomas, alterations of chromosome 22 can be found, and the NF2 (neurofibromatosis type 2) gene, in particular, is of great interest as a putative gene involved in meningioma. Because the NF2 gene is not mutated in all meningiomas, additional genes may be involved. Instead of looking for alterations directly at the DNA level, we used the immune response of meningioma patients to identify immunogenic antigens that may be associated with the disease. We screened a fetal brain cDNA expression library with sera pools from different patients bearing meningioma classified according to the three WHO grades, using the serological identification of antigens by recombinant expression cloning immunological screening method. Here, we report the finding of a new tankyrase related protein. We found 16 overlapping clones with homologies to tankyrase when we screened the library with the common-type meningioma sera pool and 2 such clones when we screened the library with the atypical meningioma sera. The anaplastic meningioma sera did not identify any tankyrase-related clones. We tested some of the newly identified clones with 13 single sera, 6 of which (37.5%) reacted positively with the tankyrase-related clones. In addition, we screened the tankyrase-related clone with six sera pools from individuals without obvious disease. Although 1 of 24 (4.2%) normal sera reacted with the tankyrase related clone, we found a striking difference in the frequency of reactivity to this clone by sera from patients bearing tumors corresponding to the three WHO meningioma grades; common-type sera was the most frequently reactive. Northern blot analysis demonstrates expression of the novel tankyrase gene in two common type meningiomas from patients with immune response. PMID- 11205899 TI - A conditionally replicative adenovirus with enhanced infectivity shows improved oncolytic potency. AB - The absence or the presence of low levels of the Coxsackievirus and adenovirus receptor (CAR) on several tumor types might limit the efficacy of recently proposed tumor-specific or conditionally replicative adenoviruses (CRAds). To address this issue, we used a genetic modification of the fiber knob in the context of an E1A-defective CRAd to allow CAR-independent target cell infection as a means to enhance oncolytic potency. Such infectivity-enhanced CRAd showed higher replication, more efficient infection, and lysis of tumor cells in vitro. Of note, the improved antitumor effect of the fiber-modified CRAd could be demonstrated in vivo. We conclude that the combination of genomic modification to achieve tumor-selective replication and capsid modification to enhance infectivity yields more potent oncolytic adenoviruses for use in cancer treatment. PMID- 11205900 TI - Dendritic cells transduced with full-length wild-type p53 generate antitumor cytotoxic T lymphocytes from peripheral blood of cancer patients. AB - Accumulation of wild-type or mutant p53 protein occurs in approximately 50% of human malignancies. This overexpression may generate antigenic epitopes recognized by CTLs. Because normal cells have undetectable levels of p53, these CTLs are likely to be tumor specific. Here, for the first time, we test the hypothesis that full-length wild-type p53 protein can be used for generation of an immune response against tumor cells with p53 overexpression. T cells obtained from nine HLA-A2-positive cancer patients and three HLA-A2-positive healthy individuals were stimulated twice with dendritic cells (DCs) transduced with an adenovirus wild-type p53 (Ad-p53) construct. Significant cytotoxicity was detected against HLA-A2-positive tumor cells with accumulation of mutant or wild type p53 but not against HLA-A2-positive tumor cells with normal (undetectable) levels of p53 or against HLA-A2-negative tumor cells. This response was specific and mediated by CD8+ CTLs. These CTLs recognized HLA-A2-positive tumor cells expressing normal levels of p53 protein after their transduction with Ad-p53 but not with control adenovirus. Stimulation of T cells with Ad-p53-transduced DCs resulted in generation of CTLs specific for p53-derived peptide. These data demonstrate that DCs transduced with the wild-type p53 gene were able to induce a specific antitumor immune response. This offers a new promising approach to immunotherapy of cancer. PMID- 11205901 TI - Neutron or photon irradiation for prostate tumors: enhancement of cytokine therapy in a metastatic tumor model. AB - We have shown that implantation of human prostate carcinoma PC-3 cells in the prostates of nude mice led to the formation of prostate tumors with metastases to para-aortic lymph nodes. We found that day 6 prostate tumors were responsive to systemic injections of interleukin 2 (IL-2) therapy. We have now investigated the combination of primary tumor irradiation and IL-2 for metastatic prostate cancer in this preclinical tumor model. The effect of neutron radiation was compared with that of photon radiation. Advanced prostate tumors (approximately 0.4 cm) were irradiated, and a day later, mice were treated with systemic IL-2 for three weekly cycles. In separate experiments, mice were either sacrificed on day 30 to assess prostate tumor size and tumor histology or followed for survival. A dose dependent inhibition of prostate tumor growth was caused either by photons or neutrons, but neutrons were more effective than photons with a relative biological effectiveness of 2. The tumor inhibition obtained with 250 cGy neutrons and 500 cGy photons was significant (>75%) and was further increased (> or = 90%) by addition of IL-2 therapy. In survival studies, the combination of radiation and IL-2 showed a significant survival advantage compared with untreated mice (P < or = 0.005) or radiation alone (P < or = 0.003) and an increase in median survival compared with IL-2 alone. Histologically, the combined regimen resulted in a greater degree of tumor destruction, inflammatory response, and vascular damage than that observed with each modality alone. After this combined treatment, no tumor was histologically detected in the para-aortic lymph nodes of these mice, and the lymph nodes were significantly smaller. These findings showed that primary tumor irradiation, either with neutrons or photons, enhanced IL-2 therapeutic effect for the treatment of advanced prostate cancer. This combined modality induced an antitumor response that controlled the growth of prostate tumors and their metastases. PMID- 11205902 TI - Overexpression of the ATP-binding cassette half-transporter, ABCG2 (Mxr/BCrp/ABCP1), in flavopiridol-resistant human breast cancer cells. AB - We sought to characterize the interactions of flavopiridol with members of the ATP-binding cassette (ABC) transporter family. Cells overexpressing multidrug resistance-1 (MDR-1) and multidrug resistance-associated protein (MRP) did not exhibit appreciable flavopiridol resistance, whereas cell lines overexpressing the ABC half-transporter, ABCG2 (MXR/BCRP/ABCP1), were found to be resistant to flavopiridol. Flavopiridol at a concentration of 10 microM was able to prevent MRP-mediated calcein efflux, whereas Pgp-mediated transport of rhodamine 123 was unaffected at flavopiridol concentrations of up to 100 microM. To determine putative mechanisms of resistance to flavopiridol, we exposed the human breast cancer cell line MCF-7 to incrementally increasing concentrations of flavopiridol. The resulting resistant subline, MCF-7 FLV1000, is maintained in 1,000 nM flavopiridol and was found to be 24-fold resistant to flavopiridol, as well as highly cross-resistant to mitoxantrone (675-fold), topotecan (423-fold), and SN-38 (950-fold), the active metabolite of irinotecan. Because this cross resistance pattern is consistent with that reported for ABCG2-overexpressing cells, cytotoxicity studies were repeated in the presence of 5 microM of the ABCG2 inhibitor fumitremorgin C (FTC), and sensitivity of MCF-7 FLV1000 cells to flavopiridol, mitoxantrone, SN-38, and topotecan was restored. Mitoxantrone efflux studies were performed, and high levels of FTC-reversible mitoxantrone efflux were found. Northern blot and PCR analysis revealed overexpression of the ABCG2 gene. Western blot confirmed overexpression of ABCG2; neither P glycoprotein nor MRP overexpression was detected. These results suggest that ABCG2 plays a role in resistance to flavopiridol. PMID- 11205903 TI - Increased fatty acid synthase is a therapeutic target in mesothelioma. AB - Many common human cancer tissues express high levels of fatty acid synthase (FAS), the primary enzyme for the synthesis of fatty acids, and the differential expression of FAS between normal and neoplastic tissues has led to the consideration of FAS as a target for anticancer therapy. To investigate the potential of targeting FAS for the treatment of pleural mesothelioma, we first determined whether FAS is overexpressed in human mesothelioma. By immunohistochemistry, we found 22 of 30 human mesothelioma tissue samples tested to express significantly increased levels of FAS compared with normal tissues, including mesothelium. To further explore FAS as a therapeutic target in mesothelioma, we established a nude mouse xenograft model for human mesothelioma using the H-Meso cell line. The i.p. xenografts of this cell line have high levels of FAS expression and fatty acid synthesis pathway activity and grow along mesothelial surfaces in a manner similar to the growth pattern of human mesothelioma. Growth of these tumor xenografts was essentially abolished in mice treated with weekly i.p. injections of C75, a synthetic, small molecule inhibitor of FAS, at levels that resulted in no significant systemic toxicity except for reversible weight loss. These results suggest that FAS may be an effective target for pharmacological therapy in a high proportion of human mesotheliomas. PMID- 11205904 TI - Differential sensitivity of various pediatric cancers and squamous cell carcinomas to lovastatin-induced apoptosis: therapeutic implications. AB - 3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase is the rate-limiting enzyme of the mevalonate pathway, the diverse array of end products of which are vital for a variety of cellular functions, including cholesterol synthesis and cell cycle progression. We showed previously that this enzyme holds a critical role in regulating tumor cell fate, including cell death, as its expression is down regulated in response to retinoic acid, a potent anticancer therapeutic. Indeed, direct inhibition of HMG-CoA reductase with lovastatin, a competitive inhibitor of this enzyme, induced a pronounced apoptotic response in neuroblastoma and acute myeloid leukemic cells. We have now extended this work and evaluated a wide variety and large number of tumor-derived cell lines for their sensitivity to lovastatin-induced apoptosis. These cell lines were exposed to a wide range (0 100 microM) of lovastatin for 2 days and assayed for cell viability using the 3,4,5-dimethyl thiazlyl-2,2,5-diphenyltetrazolium bromide assay and the induction of apoptosis by flow cytometric and ultrastructural analyses. Lovastatin induced a pronounced apoptotic response in cells derived from juvenile monomyelocytic leukemia, pediatric solid malignancies (rhabdomyosarcoma and medulloblastoma), and squamous cell carcinoma of the cervix and of the head and neck. Interestingly, the subset of malignancies that are particularly sensitive to lovastatin-induced apoptosis correspond to those tumor subtypes that are sensitive to the biological and antiproliferative effects of retinoids in vitro. The nature of the biologically active form of lovastatin has been challenged recently as the growth-inhibitory effects of this drug were attributed to its prodrug lactone form that does not inhibit HMG-CoA reductase function. In this report, we demonstrate that the apoptotic properties of lovastatin are triggered by the open ring acid form that is a potent inhibitor of HMG-CoA reductase activity. Thus, we have identified a subset of tumors that are sensitive to lovastatin-induced apoptosis and show HMG-CoA reductase as a potential therapeutic target of these cancers. PMID- 11205905 TI - Pharmacological determinants of 9-aminocamptothecin cytotoxicity. AB - The camptothecins are a group of anticancer agents with a unique mechanism of action: poisoning of eukaryotic DNA topoisomerase I. 9-aminocamptothecin (9-AC), a potent water-insoluble derivative of camptothecin, is currently undergoing clinical testing. The kinetics of the active derivative 9-AC lactone in cell culture media was defined, and then 9-AC cytotoxicity against human breast (MCF 7), bladder (MGH-U1), and colon (HT-29) cancer cell lines was studied. The relationship between cytotoxic effects, drug concentration, and exposure time was then explored. For all of the three cell lines, 9-AC cytotoxicity increased with both higher drug concentrations and longer exposure times. However, when the duration of exposure was less than 24 h, cytotoxicity was limited and less than 1 log of cell killing occurred, even with very high drug concentrations. Minimal cell killing was also observed unless 9-AC concentrations exceeded a threshold of 2.7 nM. No fixed relationship between the survival fraction and the area under the drug concentration-time curve could be modeled that would fit all of the three cell lines. However, data for the three cell lines from the multiple exposure time experiments were fitted very well to the pharmacodynamic model C(n)t = k (r2, 0.90-0.99), where C is the drug concentration, n is the drug concentration coefficient, and t is the exposure time. For the three cell lines, to kill 1 log of cells, 0.30 < n < 0.85, which indicated that duration of exposure was more important than concentration. Our data support the use of 9-AC by infusion for 24 h or longer in clinical studies providing target plasma concentrations can be achieved. PMID- 11205906 TI - Single-Dose versus fractionated radioimmunotherapy of human colon carcinoma xenografts using 131I-labeled multivalent CC49 single-chain fvs. AB - The prospects of radiolabeled antibodies in cancer detection and therapy remain promising. However, efforts to achieve cures, especially of solid tumors, with the systemic administration of radiolabeled monoclonal antibodies (MAbs) have met with limited success. Using genetic engineering techniques, MAbs have been tailored to improve the therapeutic index (tumor:normal tissue ratio) in clinical radioimmunotherapy. In the present study, we investigated the potential of tetravalent ([sc(Fv)2]2) and divalent [sc(Fv)2] single chain Fvs of MAb CC49 for therapy in athymic mice bearing s.c. LS-174T human colon carcinoma xenografts. Mice received 1,000 microCi of 131I-labeled [sc(Fv)2]2 or 131I-labeled sc(Fv)2, either as a single injection on day 6 or as four injections (250 microCi each) on days 6, 7, 8, and 9; the day of tumor implantation was taken as day 0. The median survival for the control group was 26 days. Comparisons of single and fractionated therapeutic regimens showed median survival as 32 (P < 0.001) and 53 days (P < 0.0001), respectively for [sc(Fv)2]2 and 26 (P > 0.5) and 38 days (P < 0.0001), respectively for sc(Fv)2 when compared with the control groups. The time for the quadrupling of tumor volume for single and fractionated therapeutic treatments were: 9.0 +/- 0.8 and 21.1 +/- 2.9 days respectively for sc(Fv)2; 16.6 +/- 1.9 and 32.9 +/- 2.7 days respectively for [sc(Fv)2]2; and 8.3 +/- 0.7 and 8.4 +/- 0.6 days respectively for the control group. No 131I-labeled systemic toxicity was observed in any treatment groups. The results show that radioimmunotherapy delivery for sc(Fv)2 and [sc(Fv)2]2 in a fractionated schedule clearly presented a therapeutic advantage over single administration. The treatment group receiving tetravalent scFv showed a statistically significant prolonged survival with both single and fractionated administrations suggesting a promising prospect of this reagent for cancer therapy and diagnosis in MAb-based radiopharmaceuticals. PMID- 11205907 TI - Ecteinascidin 743 induces protein-linked DNA breaks in human colon carcinoma HCT116 cells and is cytotoxic independently of topoisomerase I expression. AB - Ecteinascidin 743 (Et743; NSC 648766) is a potent antitumor agent presently in clinical trials. Et743 selectively alkylates guanine N2 from the minor groove of duplex DNA and bends the DNA toward the major groove. This differentiates Et743 from other DNA-alkylating agents presently in the clinic. To date, the cellular effects of Et743 have not been elucidated. Recently, Et743 DNA adducts have been found to suppress gene expression selectively and to induce topoisomerase I (top1) cleavage complexes in vitro and top1-DNA complexes in cell culture. In the present study, we characterized the DNA damage and the cell cycle response induced by Et743 in human colon carcinoma HCT116 cells. Alkaline elution experiments demonstrated that micromolar concentrations of Et743 produced comparable frequencies of DNA-protein cross-links and DNA single-strand breaks. The single-strand breaks were protein-cross-linked and were not associated with detectable DNA double-strand breaks. By contrast with camptothecin, these lesions persisted for several hours after drug removal and were not formed at 4 degrees C. Et743 treatment induced transient p53 elevation, dose-dependent cell cycle accumulation in G2-M and in G1- and S-phase, and inhibition of DNA synthesis. The sensitivity of camptothecin-resistant mouse leukemia P388/ CPT45 cells, which fail to express detectable top1, was similar to the sensitivity of wild-type P388 cells, suggesting that top1 is not a critical target for the antiproliferative activity of Et743. PMID- 11205908 TI - Single-cell cytotoxicity with radiolabeled antibodies. AB - Previous studies demonstrated the effective, antigen-specific killing of Raji B lymphoma cells in vitro by radiolabeled anti-CD74, attributable largely to the high level of uptake, of approximately 10(7) antibody (Ab) molecules/cell/ day. This Ab is rapidly delivered to lysosomes for catabolism, so the radionuclide delivered accumulates primarily in lysosomes. In this study, we have tested Abs that bind to the same target cells in similar amounts, but remain primarily on the cell surface, to compare the potency of radioactivity delivered to the cell surface versus the cytoplasm. The Abs tested were anti-major histocompatibility complex class II and anti-CD20. 111In-labeled conjugates made with these two Abs killed cells very effectively and specifically, with 100% kill of sample of 5 x 10(5) cells. Because these Abs remain primarily on the cell surface, it would be predicted that residualizing radiolabels, which are trapped in lysosomes after Ab catabolism, would not be required, and this was observed, i.e., these two Abs were effective when labeled with either 125I or 131I, using conventional iodination, as well as with the residualizing label 111In-labeled DTPA. These results are in contrast to results obtained with anti-CD74, which required a residualizing radiolabel for effectiveness. The uptake of these radionuclides, in cpm/cell, was monitored, and this allowed estimation of the radiation dose delivered; the cytotoxicity observed was consistent with the estimated radiation dose delivered. To establish the generality of the results, we also demonstrated that 111In-labeled anti-CD74 effectively killed three other B-lymphoma cell lines, in addition to Raji and the adherent melanoma cell line SK-MEL-37. By using more potent radionuclides or conjugates of higher specific activity, this approach might be effective with other, lower density antigens. PMID- 11205909 TI - Use of dendritic cells to immunize against cancers overexpressing p53. PMID- 11205910 TI - In vitro synergistic interactions between the cisplatin analogue nedaplatin and the DNA topoisomerase I inhibitor irinotecan and the mechanism of this interaction. AB - Among the numerous clinical regimens used in combination chemotherapy, synergy is particularly marked in combinations containing cisplatin (CDDP). However, the clinical use of CDDP is sometimes limited due to its nephrotoxicity. Nedaplatin (NDP) is a second-generation platinum complex with reduced nephrotoxicity that may substitute for CDDP or even surpass it for use in combination with other drugs. We investigated the effects of combinations of NDP and other anticancer drugs on the growth of human small cell lung cancer cells (SBC-3) and non-small cell lung cancer cells (PC-14) using a three-dimensional analysis model. Among the combinations tested, the combination of NDP and irinotecan (CPT-11) showed the most marked synergistic interaction, and the synergism has also been observed against PC-14 cells. With regard to treatment schedule, a remarkable synergistic interaction was produced by concurrent exposure to NDP and CPT-11. On the other hand, sequential exposure to the two drugs led only to additivity. To analyze the interaction between the drugs, the effect of NDP on the 7-ethyl-1-hydroxy-CPT (the active form of CPT-11)-induced inhibitory effect on DNA topoisomerase I was examined. The topoisomerase I-inhibitory effect of 7-ethyl-1-hydroxy-CPT was enhanced 10-fold in the presence of NDP at microgram/milliliter concentrations. These biochemical interactions might be responsible for the synergistic interaction between NDP and CPT-11. These results suggest that the combination of NDP with CPT-11 may be clinically useful for the chemotherapy of lung cancer. PMID- 11205911 TI - Differential effects of adenovirus-p16 on bladder cancer cell lines can be overcome by the addition of butyrate. AB - High frequency of p16 alteration and high local recurrence rate of bladder cancer make this cancer an ideal target for p16 gene therapy. However, a low transduction rate of p16 via adenoviral vector causes an inconsistent result. In this study, we have tested adenovirus-p16 in several bladder cancer cell lines and investigated a way of improving the low transduction rate. Adenovirus-p16 showed a strong antitumor effect on bladder cancer cell lines (253J and T24) with strong Coxackie-adenoviral receptor (CAR) expression but little antitumor effect on bladder cancer cell lines (J82 and HT1376) with little CAR expression. In this study, we suggest a simple way of overcoming the differential effects of the adenovirus. The addition of butyrate to media was found to increase the transduction rate of adenovirus remarkably and increase the antitumor effect of adenovirus-p16 in bladder cancer cell lines with little CAR expression. Butyrate effects were related with increased CAR expression on the cell surface as well as increased transgene expression from adenoviral vector. From these observations, application of adenovirus-p16 gene therapy with butyrate can overcome the obstacle of low gene transfer and enhance the antitumor effect of adenovirus-p16 in bladder cancer. PMID- 11205912 TI - The effects of KNK437, a novel inhibitor of heat shock protein synthesis, on the acquisition of thermotolerance in a murine transplantable tumor in vivo. AB - A newly synthesized reagent, KNK437, has been found specifically to inhibit the synthesis of heat shock proteins in vitro. In this study, we investigated the effects of KNK437 on the synthesis of heat shock proteins and the induction of thermotolerance in transplantable tumors in vivo. SCC VII cells were grown in vivo and transplanted into C3H/He mice. The concentrations of KNK437 in the tumors and the sera of the mice were examined by high-performance liquid chromatography. Hsp72 synthesis was examined by Western immunoblot analysis. The response to hyperthermia was evaluated in terms of the delay in tumor growth. KNK437 had low toxicity in vivo. The concentration of KNK437 in the tumors gradually increased and reached a peak 6 h after i.p. injection. Hsp72 were synthesized 8 h after hyperthermia at 44 degrees C for 10 min, and their synthesis was inhibited by administration of KNK437 6 h before hyperthermia. At a concentration of 200 mg/kg, KNK437 alone showed no antitumor effects and did not increase the thermosensitivity of nontolerant tumors. The same dose of KNK437 enhanced the antitumor effects of fractionated heat treatment at 44 degrees C in a synergistic manner. This study strongly suggests the inhibition of thermotolerance via the inhibition of HSP72 in vivo. The inhibition of thermotolerance by KNK437 may help to improve the efficacy of clinical fractionated hyperthermia. PMID- 11205913 TI - Immunotherapy of bladder cancer using autologous dendritic cells pulsed with human lymphocyte antigen-A24-specific MAGE-3 peptide. AB - Recent investigations have demonstrated the efficacy of autologous dendritic cells (DCs) pulsed with tumor antigens to generate tumor-specific CTLs against cancer cells. Melanoma antigens (MAGE) are a family of tumor-specific antigens shown to be expressed in various tumors, including bladder cancers and melanoma, but not in normal tissues except for the testis. Because invasive bladder cancers are frequently reported to express MAGE, we explored the possibility of establishing a new immunotherapeutic modality against advanced bladder cancer using autologous DCs pulsed with one of the MAGE-3 epitope peptides (IMPKAGLLI), which is synthesized to bind specifically to HLA-A24. A MAGE-3-expressing bladder cancer cell line, FY, was newly established from a lymph node metastasis of bladder cancer in a HLA-A24+ patient. The FY cell-specific CTL response was significantly higher when CTL was induced by autologous DCs pulsed with IMPKAGLLI than by FY cells alone or by nonpulsed DCs in vitro. A total of four HLA-A24+ patients with advanced MAGE-3+ bladder cancers were treated with s.c. injections of autologous DCs pulsed with IMPKAGLLI every 2 weeks for a minimum of 6 and a maximum of 18 times. Three of four patients showed significant reductions in the size of lymph node metastases and/or liver metastasis. No significant untoward side effects were noted in these patients. This study indicated that, at sometime in the future, tumor-specific DC-based cancer immunotherapy may be useful as an additional treatment modality against advanced bladder cancer. PMID- 11205914 TI - A phase I study of irinotecan in pediatric patients: a pediatric oncology group study. AB - A Phase I trial of irinotecan was performed to determine the maximum tolerated dose (MTD), the dose-limiting toxicities (DLTs), and the incidence and severity of other toxicities in children with refractory solid tumors. Thirty-five children received 146 courses of irinotecan administered as a 60-min i.v. infusion, daily for 5 days, every 21 days, after premedication with dexamethasone and ondansetron. Doses ranged from 30 mg/m2 to 65 mg/m2. An MTD was defined in heavily pretreated and less-heavily pretreated (i.e., two prior chemotherapy regimens, no prior bone marrow transplantation, and no radiation to the spine, skull, ribs, or pelvic bones) patients. Myelosuppression was the primary DLT in heavily pretreated patients, and diarrhea was the DLT in less-heavily pretreated patients. The MTD in the heavily pretreated patient group was 39 mg/m2, and the MTD in the less-heavily pretreated patients was 50 mg/m2. Non-dose-limiting diarrhea that was well controlled and of brief duration was observed in approximately 75% of patients. A partial response was observed in one patient with neuroblastoma, and in one patient with hepatocellular carcinoma. Stable disease (4-20 cycles) was observed in seven patients with a variety of malignancies including neuroblastoma, pineoblastoma, glioblastoma, brainstem glioma, osteosarcoma, hepatoblastoma, and a central nervous system rhabdoid tumor. In conclusion, the recommended Phase II dose of irinotecan administered as a 60-min i.v. infusion daily for 5 days, every 21 days, is 39 mg/m2 in heavily treated and 50 mg/m2 in less-heavily treated children with solid tumors. PMID- 11205915 TI - A phase II trial of bryostatin 1 in the treatment of metastatic colorectal cancer. AB - Current chemotherapy for patients with advanced colorectal cancer is relatively ineffective and may be associated with significant toxicity. Bryostatin 1 (bryo 1) influences cell proliferation, intracellular metabolism and signaling, differentiation, and apoptosis in human cancer cell lines via modulation of protein kinase C (PKC) activity. This trial investigates the efficacy and toxicity of bryo 1 as a novel therapeutic agent for patients with advanced colorectal cancer who have had previous 5-fluorouracil therapy. The primary end point was tumor response to bryo 1. Toxicity was also assessed. Twenty-eight patients with advanced colorectal cancer were enrolled. The mean age was 59 years (range, 38-76), with 16 men and 12 women, and good minority representation (11 African-Americans). The first 10 patients initially received 25 microg/m2 of bryo 1 weekly as a 24-h infusion for 3 weeks of every 4-week cycle, with dose escalation to 35 microg/m2 starting with the second cycle. The remaining patients were started at 35 microg/m2 and escalated to 40 microg/m2, if toxicity was minimal. Twenty-five patients were evaluable for objective tumor response, and complete data on toxicity were collected on 26 patients. No partial or complete tumor responses were observed. All 25 patients had disease progression within four cycles. Myalgia was the most common toxicity. Myelosuppression was not seen. bryo 1 as a weekly 24-h continuous infusion lacks single-agent antitumor activity in advanced colorectal cancer. Toxicity differs from that of traditional chemotherapeutic drugs. PMID- 11205916 TI - A phase I and pharmacokinetic study of the novel aza-anthracenedione compound BBR 2778 in patients with advanced solid malignancies. AB - BBR 2778 is a novel aza-anthracenedione with no cardiotoxicity in preclinical models. This Phase I dose escalation trial of BBR 2778 was conducted to determine the maximum tolerated dose, the dose-limiting toxicity, and the pharmacokinetic profile of BBR 2778 in patients with advanced solid tumors. BBR 2778 was given in three consecutive weekly 30-min i.v. infusions over a 4-week cycle (cy). Thirty patients (pts) were treated with BBR 2778 at doses ranging from 5 to 150 mg/m2/week. The dose levels 5, 10, 16.5, 25, 37.5, 75, 112.5, and 150 mg/m2/week were investigated in 4 pts (9 cy), 3 pts (3 cy), 3 pts (5 cy), 6 pts (9 cy), 1 pt (1 cy), 4 pts (9 cy), 6 pts (18 cy), and 3 pts (4 cy), respectively. The dose limiting toxicity was neutropenia, typically occurring at day 14. Other toxicities were mild to moderate and were principally thrombocytopenia, lymphopenia, alopecia, nausea, and vomiting and blue coloration of the skin and urine. No significant cardiac toxicity was observed. The plasma dose concentration curve fitted a biexponential profile, with a rapid distribution phase followed by a prolonged elimination phase (mean t1/2,z, 12 h). BBR 2778 displayed a large volume of distribution (range, 9.7-29.7 l/kg) with a high plasma clearance rate (0.75-1.31 l/h/kg). Less than 10% of the dose was recovered in urine as unchanged drug. The maximum tolerated dose was 150 mg/m2/week for 3 weeks, every 4 weeks. On the basis of this study, the recommended dose for Phase II studies is 112.5 mg/m2/week days 1 and 8 with individual optional administration at day 15, every 4 weeks. Antitumor activity was observed in patients with breast, small cell lung carcinoma, and facial cylindroma. This trial showed that BBR 2778 has a manageable toxicity profile on a weekly schedule. This lead compound of the aza-anthracenedione family shows promising antitumor activity and deserves Phase II investigation in patients with high risk of cumulative cardiotoxicity, such as anthracycline-pretreated breast cancer patients. PMID- 11205917 TI - Early detection of lung cancer: clinical perspectives of recent advances in biology and radiology. AB - Lung cancer is the most common cause of cancer death in developed countries. The prognosis is poor, with less than 15% of patients surviving 5 years after diagnosis. The poor prognosis is attributable to lack of efficient diagnostic methods for early detection and lack of successful treatment for metastatic disease. Most patients (>75%) present with stage III or IV disease and are rarely curable with current therapies. Within the last decade, rapid advances in molecular biology, pathology, bronchology, and radiology have provided a rational basis for improving outcome. These advancements have led to a better documentation of morphological changes in the bronchial epithelium before development of clinical evident invasive carcinomas. This has changed our concept of lung carcinogenesis and emphasized the multistep carcinogenesis approach on several levels. Combined with the technical developments in bronchoscopic techniques, e.g., laser-induced fluorescence endoscope (LIFE) bronchoscopy, we now have improved methods to localize preinvasive and early-invasive bronchial lesions. With the LIFE bronchoscope, a new morphological entity (angiogenic squamous dysplasia) has been recognized, which might be an important biomarker and target for antiangiogenic chemopreventive agents. To reduce the mortality of lung cancer, these new technologies have been taken into the clinic in different scientific settings. The use of low-dose spiral computed tomography in the screening of a high-risk population has demonstrated the possibility of diagnosing small peripheral tumors that are not seen on conventional X-ray. A shift in the therapeutic paradigm from targeting advanced clinically manifest lung cancer toward asymptomatic preinvasive and early-invasive cancer is occurring. The present article reviews the recent advances in the diagnosis of preinvasive and early-invasive cancer to identify biomarkers for early detection of lung cancer and for chemoprevention studies. PMID- 11205918 TI - Simultaneous immunomagnetic CD34+ cell selection and B-cell depletion in peripheral blood progenitor cell samples of patients suffering from B-cell non Hodgkin's lymphoma. AB - The reduction of residual tumor cells is one of the main targets of leukapheresis product (LP) processing. Immunomagnetic enrichment/selection of CD34+ progenitor cells (Baxter Isolex 300i) can achieve a reduction of contaminating B-cells of approximately 2-3 logs in B-cell non-Hodgkin's lymphoma patients. Specific release of the enriched CD34+ cells (stem cell releasing agent PR34+; Baxter) and the use of antibody-coated immunobeads targeted against B-cell markers (CD10, CD19, CD20, CD22, CD23, and CD37) during this procedure allows the GMP-like simultaneous capture of residual B cells within a closed system. This combination of two purging techniques enhances the B-cell depletion capacity up to 4.5 logs. By performing 10 clinical-scale purging procedures, we could show that the simultaneous immunomagnetic purging method is easy to perform and highly efficient. We evaluated B-cell log depletion by flow cytometry for cases with marker-positive cells detectable before and after the purging procedure. The mean reduction of B-cells in these cases was 3.5 logs; the mean CD34+ cell yield and purity were 47 and 92%. Using three LPs, we tested the procedure on a modified Baxter Isolex 300i device with software adaptations for this procedure (software version 2.0) in direct comparison with CD34+ cell selection only, using the former version (version 1.12). The CD34+ cell yield was 49% (40-54%) for the CD34+ cell selection and 51% (19-72%) for simultaneous double selection. The mean purity was 96% for CD34+ cell selection and 98% for simultaneous double selection. B-cell depletion was 1.9 logs for CD34+ cell selection, and after simultaneous double selection, the B-cell content was decreased by 3.7 log steps (P = 0.0495). Clinical application of double-purged cells has not prolonged the hematopoietic recovery times after high-dose therapy as compared with nonpurged peripheral blood progenitor cell autotransplants. In conclusion, we could show that the simultaneous double selection protocol developed leads to a highly increased B-cell purging efficacy when compared with CD34+ cell selection without any negative effects regarding CD34+ cell yield and engraftment times after high dose therapy. PMID- 11205920 TI - Weekly irinotecan and cisplatin in advanced non-small cell lung cancer: a multicenter phase II study. AB - The combination of weekly irinotecan (CPT-11) and monthly cisplatin has shown promising activity in advanced non-small cell lung cancer (NSCLC) in previous Phase I and II studies. However, same-day administration of these agents may better exploit their therapeutic synergy and minimize toxicities. This multicenter Phase II study was undertaken to evaluate the efficacy and safety of a combination of weekly CPT-11 and weekly cisplatin in patients with advanced NSCLC. Patients with chemotherapy-naive stage IIIB or IV NSCLC were treated with repeated cycles of therapy comprising weekly treatment with both cisplatin and CPT-11 for 4 weeks, followed by a 2-week rest. The starting doses of CPT-11 and cisplatin were 65 and 30 mg/m2, respectively. Treatment was continued until the occurrence of disease progression, unacceptable toxicity, or a maximum of six cycles. Fifty patients were enrolled. The median age was 59 years (range, 44-79 years). Eastern Cooperative Oncology Group performance status was 0 in 22 patients, 1 in 19 patients, and 2 in 9 patients. Seven and 43 patients had stages IIIB and IV disease, respectively. Five patients had brain metastasis. Patients received a median of three 6-week cycles (range, 1-6). The objective response rate was 36% (18 of 50; 95% confidence interval, 24-54%) and included 18 partial responses. Median time to tumor progression was 6.9 months (range, 0.6-15.2). The median survival was 11.6 months (range, 0.16-21.9 months), and the 1-year survival rate was 46%. Grade 3/4 nonhematological toxicities included vomiting (12%) and diarrhea (26%). Grade 3/4 hematological toxicities included anemia (14%), neutropenia (26%), and thrombocytopenia (14%). Relative dose intensities for CPT-11 and cisplatin were 89 and 62%, respectively. Weekly combined administration of CPT-11 and cisplatin achieved a promising overall response rate, median time to tumor progression, and median survival in patients with stage IIIB/IV NSCLC. The regimen was well tolerated, and the planned dose intensity was well maintained. Further evaluation of this combination in NSCLC is warranted. PMID- 11205919 TI - A phase I clinical, pharmacological, and biological trial of interleukin 6 plus granulocyte-colony stimulating factor after ifosfamide, carboplatin, and etoposide in children with recurrent/refractory solid tumors: enhanced hematological responses but a high incidence of grade III/IV constitutional toxicities. AB - A Phase I trial was conducted to determine the safety, biological activity, and hematopoietic recovery by the combination of interleukin 6 (IL-6) and granulocyte colony stimulating factor (G-CSF) after myelosuppressive chemotherapy in children. Patients <22 years of age at diagnosis with either recurrent or refractory solid tumors received ifosfamide 1,800 mg/m2/day x 5 days, carboplatin 400 mg/m2/ day x 2 days, and etoposide 100 mg/m2/day x 5 days, followed by daily s.c. G-CSF (5 microg/kg/day) and IL-6 (2.5, 3.75, or 5.0 microg/kg/day). Pharmacokinetic, proinflammatory mediator levels, hematopoietic colony assays, and cytokine receptor expression studies were performed during course one. Nineteen patients were evaluable for toxicity and received IL-6 at doses of 2.5 (n = 8), 3.75 (n = 5), or 5.0 (n = 6) microg/kg/day. Dose-limiting constitutional toxicity occurred in two of six patients at 5.0 microg/kg/day, two of five patients at 3.75 microg/kg/day, and two of eight patients at 2.5 microg/kg/day. The maximum tolerated dose (MTD) exceeded the lowest dose tested. Because of lack of drug availability, an MTD was not established. The maximum concentration of IL 6 (2.5 microg/kg/day) was 0.799 +/- 1.055 ng/ml (mean +/- SD). During the first course, the median time to absolute neutrophil count > or = 1,000/mm3 and platelets > or = 100,000 mm3 was estimated at 19 and 23 days, respectively. Peripheral blood progenitor cells expressing receptors to IL-3, IL-6, and G-CSF increased significantly over baseline (P < 0.05). After the first dose of IL-6, IFN-gamma levels were abnormal in 13 patients, and IL-1beta levels were abnormal in 10 patients. IL-6 has a high incidence of constitutional toxicity and a lower MTD in children compared with adults. In vivo use of IL-6 in children after chemotherapy remains limited. However, IL-6 may be more optimally investigated in children under ex vivo conditions. PMID- 11205921 TI - Elevated caspase-3 activity in peripheral blood T cells coexists with increased degree of T-cell apoptosis and down-regulation of TCR zeta molecules in patients with gastric cancer. AB - To evaluate the mechanisms of T-cell dysfunction in patients with gastric cancer, we investigated the caspase activity of T cells, the induction of spontaneous T cell apoptosis, the expression of T-cell receptor (TCR) zeta molecules, and the ability of T cells to produce cytokines in peripheral blood lymphocytes from patients (n = 22) and healthy controls (n = 14). The caspase-3 activity of T cells was studied as the protease activity of caspase-3 using the cell-permeable substrate of PhiPhiLux G1D2. Flow cytometric analysis was performed with triple staining by annexin V-FITC, propidium iodide, and CD3-R-phycoerythrin-Cy5 for the detection of T-cell apoptosis and with intracellular staining using permeabilized cells for the expression of TCR-zeta molecules. IFN-gamma and tumor necrosis factor alpha production from T cells was evaluated in response to anti-CD3 stimulation. Caspase-3 activity of peripheral blood T cells from patients with advanced disease was significantly increased compared with that from controls [15.5 +/- 3.6 mean fluorescence intensity (MFI) versus 11.5 +/- 3.3 MFI; P = 0.0068]. Parallel to this, the apoptosis of peripheral blood T cells from patients with advanced disease was significantly higher than for those from controls (16.5 +/- 15.5% versus 4.8 +/- 2.7%; P = 0.010). Furthermore, the expression of TCR-zeta molecules in patients with advanced disease was significantly decreased in comparison with that of the controls (41.0 +/- 13.9 MFI versus 56.7 +/- 16.3 MFI; P = 0.014), and this decreased expression coexisted with impaired IFN-gamma (42.4 +/- 43.2 pg/ml versus 1,757.4 +/- 2449.0 pg/ml; P = 0.031) and tumor necrosis factor alpha (682.6 +/- 519.3 pg/ml versus 1,686.0 +/- 1,533.7 pg/ml; P = 0.041) production of T cells. Thus, peripheral blood T cells from gastric cancer patients simultaneously exhibit an elevated caspase-3 activity, an increased degree of T-cell apoptosis, a down-regulation of TCR-zeta molecules, and impaired cytokine production. These observations suggest that induction of T-cell apoptosis coexisting with a down-regulation of TCR-zeta molecules may be responsible for T-cell dysfunction in patients with gastric cancer. PMID- 11205922 TI - Independent association of angiogenesis index with outcome in prostate cancer. AB - New molecular factors have been characterized that are associated with the prognosis of prostate carcinoma patients, including p53 status and angiogenesis. We reported recently that mutant p53 (mp53) was associated with decreased expression of an endogenous inhibitor of angiogenesis, thrombospondin-1 (TSP-1), and increased microvessel density in melanoma and breast cancer. In this study, we performed a similar analysis on primary prostate carcinoma to determine whether these factors were associated with each other or patient outcomes. Paraffin-embedded specimens of 98 cases of primary prostate carcinoma were obtained and examined to confirm tissue diagnosis and Gleason scores. Carcinoma specific levels of p53, TSP-1, and tumor angiogenesis were determined using semiquantitative immunohistochemistry (IHC) methods. Acquisition of mp53 was significantly associated with decreased TSP-1 (P = 0.002) and increased angiogenesis (P < 0.0001). An angiogenesis index integrating mp53, TSP-1, and angiogenesis (CD31) scores was found to be an independent predictor of survival in univariate and multivariate analyses that included Gleason score, clinical stage, and patient age. Further validation of the angiogenesis index in prostate carcinoma may provide a new tool to stratify patient risk. PMID- 11205923 TI - The expression of G250/mn/CA9 antigen by flow cytometry: its possible implication for detection of micrometastatic renal cancer cells. AB - Monoclonal antibody (mAb) G250 is a well characterized and specific mAb to renal cell carcinoma (RCC). The gene G250 was recently cloned and was proved to be homologous to MN/CA9. The G250/MN/CA9 antigen was recently explored as a potential marker for RCC. Flow cytometry (FCM) allows quantitative analysis of cells. The present study describes a flow cytometric method to detect this antigen in human cell lines and in malignant and normal renal tissues. Twelve human carcinoma cell lines (HeLa, Colo205, HT29, BxPC3, OVCAR3, SKOV3, ACHN, A704, CAKI-2, SKRC-59, SKRC-10, and SKRC-52), 10 specimens of normal peripheral blood mononuclear cells, and 38 malignant and 36 adjacent normal renal tissues were studied. The malignant and normal renal tissues were disaggregated mechanically into a single-cell suspension, stained by mAb G250, and analyzed by FCM. All 22 of the clear cell carcinomas, 6 of 8 mixed cell carcinomas, and 3 of 6 granular cell carcinomas were positive for G250/MN/CA9 antigen. SKRC-52 and SKRC-10 were strongly positive for G250/ MN/CA9. The G250/MN/CA9 antigen could also be detected in HeLa, SKOV3, HT29, and A704 cells. One chromophobic, one chromophilic cell carcinoma, the normal renal tissues, and normal peripheral blood mononuclear cells were considered as negative. Our results further confirmed that the G250/MN/CA9 antigen was an ideal marker for RCC, especially for clear cell carcinomas, and that this antigen was present in several types of malignant cells. FCM may serve as a fast tool of immunocytochemical detection of renal cancer cells. Flow cytometric detection of renal cancer cells by using mAb G250 should be further explored. PMID- 11205924 TI - Selective immunohistochemical staining of blood and lymphatic vessels reveals independent prognostic influence of blood and lymphatic vessel invasion in early stage cervical cancer. AB - Lymphovascular space invasion was shown to play a key role in the progression of cervical cancer. Because of the absence of a specific marker for lymphatic vessels, earlier studies could not reliably distinguish between blood and lymphatic vessel invasion. By immunostaining for podoplanin, a novel marker for lymphatic endothelium, and for factor VIII-related antigen, we determined lymphatic and blood vessel invasion in tissue samples of 98 patients with cervical cancer pT1b treated by radical hysterectomy. Eleven (11.2%) specimens showed invasion of blood vessels, 20 (20.4%) showed invasion of lymphatic vessels, and 15 (15.3%) showed invasion of blood and lymphatic vessels. There was a strong association of lymphatic vessel invasion and lymph node involvement (P < 0.001). In univariate analysis, both blood and lymphatic vessel invasion failed to reach a statistically significant influence on overall survival, but a significant influence on disease-free survival was found (P = 0.0002 and P < 0.0001, respectively). In multivariate analysis of disease-free survival, only blood vessel invasion remained statistically significant (P = 0.0457). Lymphatic vessel invasion reached significance when lymph node status was excluded from the model (P = 0.0025). Both lymphatic vessel and blood vessel invasion occur frequently in early-stage cervical cancer. Determination of the vessel status may be of clinical importance because it signifies the risk of recurrent disease. PMID- 11205925 TI - Novel expression and function of peroxisome proliferator-activated receptor gamma (PPARgamma) in human neuroblastoma cells. AB - Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a member of the nuclear receptor superfamily of ligand-dependent transcription factors that has been shown to play a major role in adipocyte and monocyte/macrophage differentiation. Recent work has also suggested a role for PPARgamma in cell cycle control and/or differentiation of other cell types including breast and lung cancer cells. Using reverse transcription-PCR, we now show for the first time that human neuroblastoma (nb) cells express PPARbeta and -gamma, but not alpha. Using the LA-N-5 nb cell line, we have determined that the natural PPARgamma ligand 15-deoxy-delta prostaglandin J2, as well as the synthetic PPARgamma agonist GW1929, can stimulate the differentiation of nb cells, as evidenced by the inhibition of cell proliferation, neurite outgrowth, increased acetylcholinesterase activity, and the reduction of N-myc expression. We have also demonstrated that PPARgamma is expressed in primary nb and, furthermore, that the expression of this receptor correlates with the maturational stage of the nb cells. Taken together, these studies have implicated a role for PPARgamma in peripheral nerve cell biology and suggest that the PPARgamma signaling pathway is involved in the regulation of nb cell growth and differentiation. PMID- 11205926 TI - Cannabis arteritis revisited--ten new case reports. AB - The purpose of this paper was to revisit the old concept of cannabis arteritis first described in the 1960s and report 10 new cases. Ten male patients, with a median age of 23.7 years developed subacute distal ischemia of lower or upper limbs, leading to necrosis in the toes and/or fingers and sometimes to distal limb gangrene. Two of the patients also presented with venous thrombosis and three patients were suffering from a recent Raynaud's phenomenon. Biological test results did not show evidence of the classical vascular risk factors for thrombosis. Arteriographic evaluation in all cases revealed distal abnormalities in the arteries of feet, legs, forearms, and hands resembling those of Buerger's disease. A collateral circulation sometimes with opacification of the vasa nervorum was noted. In some cases, arterial proximal atherosclerotic lesions and venous thrombosis were observed. All patients were moderate tobacco smokers and regular cannabis users. Despite treatment with ilomedine and heparin in all cases, five amputations were necessary in four patients. The vasoconstrictor effect of cannabis on the vascular system has been known for a long time. It has been shown that delta-8- and delta-9-tetrahydrocanabinols may induce peripheral vasoconstrictor activity. Cannabis arteritis resembles Buerger's disease, but patients were moderate tobacco smokers and regular cannabis users. These cases show that prolonged use of cannabis could be an additive risk factor for juvenile and young adult arteritis. Cannabis arteritis is a forgotten and severe occlusive vascular disease occurring in young adults. Search for cannabis use may be an important tool for a better knowledge of arteritis in young smokers. PMID- 11205927 TI - Effects of estrogen therapy on arterial resistance and pulsatility in postmenopausal women. AB - The hypothesis of this study was that changes in arterial determinants of afterload due to static muscular contraction can be modified, in postmenopausal women, by estrogen replacement therapy. Two groups of 14 postmenopausal and 15 premenopausal women were enrolled. Hemodynamic changes induced by right handgrip were recorded between days 7 and 10 of the menstrual cycle in premenopausal women. The same recordings were performed in postmenopausal women, before and after receiving transdermal estrogen replacement therapy for 8 days. Handgrip was performed at 50% of maximal voluntary contraction and maintained until exhaustion. Arterial pressure and blood velocity were recorded in the resting hand with photoplethysmographic and Doppler techniques. Indices of arterial elasticity and resistance were calculated. In postmenopausal women, these indices increased during effort only slightly less after therapy than before, if the mean values and statistical significance were considered, but the most evident effect of therapy was a decrease in interindividual differences in the effort induced changes. This means that, after therapy, increases in arterial resistance and elasticity indices were appreciably prevented mainly in those postmenopausal women who, before therapy, showed the greatest increases. Differences due to therapy were negligible in postmenopausal women in whom, before estrogen replacement, increases in elasticity and resistance indices during effort were similar to those obtained in premenopausal women. After therapy, no differences were found in resting conditions in any of the investigated cardiovascular parameters. Estrogen replacement did not appreciably affect changes in some arterial afterload-related indexes during handgrip, if the average values were considered in a group of postmenopausal women, but uneven and unpredictable peaks in individual responses were cut off, with a better predictability of the responses to sustained muscular contractions, as well as of the related risk factors. PMID- 11205928 TI - Clinical characteristics influence left and right ventricular diastolic function in healthy individuals. AB - The aim of this study was to determine whether clinical characteristics have an influence on left (LV) and right ventricular (RV) diastolic function indices measured by echocardiography in healthy individuals. Five hundred and three volunteers (253 women and 250 men) aged 18-66 years (mean 36.9 +/- 11.9) who were normotensive and free of clinically apparent heart disease were included in the study. Mitral and tricuspid peak E wave and A wave velocities, E/A ratio, deceleration time (DT) of the E wave, and left ventricular isovolumetric relaxation time (IVRT) were evaluated as left and right ventricular diastolic function indices. In order to determine the effects of age, gender, body surface area (BSA), waist/hip ratio (WHR), and heart rate (HR) on left and right ventricular diastolic function indices Student's t test and correlation and linear regression analysis were used. IVRT and deceleration time of the mitral E wave (DTm) were significantly longer in men. Mitral and tricuspid A wave velocities, tricuspid E/A ratio, and deceleration time of the tricuspid E wave (DTt) were similar in both genders. Mitral and tricuspid E wave velocities and mitral E/A ratio were greater in women. Mitral E wave velocity and IVRT mostly correlated with WHR. Age was found to be the most important factor affecting mitral A wave velocity, DTm, E/A ratio, and right ventricular diastolic function indices. This study shows that age, heart rate, body surface area, and waist/hip ratio have important correlations with Doppler echocardiographic diastolic indices in normal individuals and should be considered in the evaluation of LV and RV diastolic function. PMID- 11205929 TI - Primary pulmonary hypertension in HIV patients: a systematic review. AB - The relationship between grade of pulmonary hypertension and factors associated with human immunodeficiency virus among patients with HIV infection is poorly documented. This report documents the most extensive attempt made thus far to determine whether a relationship exists between degree of pulmonary hypertension and the following conditions: HIV risk factor, degree of immunosuppression, presence or absence of AIDS, and presence or absence of liver cirrhosis. A retrospective study involving a search of the published literature on primary pulmonary hypertension among HIV cases from 1987 to 1998, using the Medline and Aidsline databases was conducted. Patients for whom secondary causes of pulmonary hypertension could be excluded were selected, and the following information for each was recorded: age, gender, risk factors for HIV infection, HIV disease stage according to the Centers for Disease Control, previous opportunistic and neoplastic diseases, CD4+ cell count (cells/L), presence or absence of liver cirrhosis, pulmonary systolic artery pressure level, and lung pathology specimens. Information about the patient's survival time was also recorded. Seventy-six patients were judged to have primary pulmonary hypertension and were included in the study. While no correlation was found between pulmonary systolic artery pressure level and CD4+ cell counts, a statistically significant difference was found between HIV-positive patients with and without AIDS as determined by the Centers for Disease Control criteria with regard to the degree of pulmonary hypertension, expressed as pulmonary systolic artery pressure level (85.4 +/- 17 mm Hg vs 71.8 +/- 15 mm Hg, p < 0.013). Although a higher PAPS was present in HIV cirrhotic patients, a statistically significant difference was not found between degree of pulmonary hypertension and evidence of hepatic cirrhosis (85 +/- 21 mm Hg vs 73.1 +/- 15 mm Hg, p < 0.062). Patients with AIDS and primary pulmonary hypertension present a higher degree of pulmonary hypertension than non AIDS patients. Pulmonary hypertension associated with HIV seems to be related to a cytokine-related stimulation and proliferation of endothelium. High levels of cytokines present in AIDS patients can favor pulmonary hypertension, but the role of a host response to HIV--determined by one or more HLA subtypes--is suspected to enhance high cytokine production levels. PMID- 11205930 TI - QT dispersion in single coronary artery disease: is there a relation between QT dispersion and diseased coronary artery or lesion localization? AB - It has been shown that QT dispersion (QTD) increases during episodes of myocardial ischemia or infarction. However, no extensive data on the relation between the diseased coronary artery or the localization of stenosis and the QTD are available. The aim of the study was to examine the relation between QTD and diseased coronary artery and lesion localization during exercise stress test in patients with single coronary artery disease without prior myocardial infarction. One hundred nineteen patients with single coronary artery disease and 53 patients with normal coronary arteries were enrolled in study. All patients underwent exercise stress test with modified Bruce protocol, and QT interval parameters were measured at rest and at minute 2 of the recovery (rec-2) period. QT dispersion at rest was found higher in all single-vessel disease groups compared with that in the control group, and corrected QT dispersion at rec-2 period was also markedly higher in left anterior descending, circumflex, and right coronary artery groups compared with that in the control group. No relation was found between QT dispersion and diseased coronary artery or the lesion localization. In conclusion, no qualitative difference was found between QT dispersion and diseased coronary artery or proximal or distal lesion localization. However, it was observed that patients with single-vessel disease had wider baseline QT dispersion as compared with that in the control group, which further increased significantly with exercise. This finding supports the idea that severity of localized ischemia rather than extent of coronary artery disease would be expected to have a greater effect on inducible QT dispersion. PMID- 11205932 TI - Scleroderma pericardial disease presented with a large pericardial effusion--a case report. AB - Scleroderma pericardial disease is usually silent and benign. The incidence of pericardial involvement in scleroderma is about 50% according to autopsy results, but symptomatic pericarditis manifests in about 16% of patients with diffuse scleroderma and in about 30% of patients with limited scleroderma. The clinically evident pericardial effusion is rare in scleroderma, although it can be detected in about 41% of patients with echocardiography. In majority of the patients, the pericardial effusion is small and not associated with symptoms. The pericardial effusion manifests usually after the manifestation of the other clinical and serologic features of scleroderma. A case of scleroderma is reported that presented with a large pericardial effusion, which antedated the other clinical and serologic features of scleroderma. The pericardial involvement in scleroderma is reviewed. PMID- 11205931 TI - Improvement of left ventricular diastolic dynamics in prediabetic stage of a type II diabetic rat model after troglitazone treatment. AB - Troglitazone, an oral antidiabetic agent, has hypoglycemic effects in insulin resistant animal models and humans. This study was conducted to evaluate its effect on left ventricular diastolic dynamics of a spontaneous diabetic (DM) rat model. Twenty DM rats and 20 age-matched nonDM rats were used, and 10 of each group were treated with troglitazone as a 0.2% food admixture for 10 weeks. At 5 and 15 weeks of age, Doppler echocardiography and M-mode echocardiography were performed. Troglitazone treatment significantly improved the left ventricular diastolic dynamics of DM rats: deceleration time (msec) of early diastolic inflow decreased significantly (treated 52 +/- 3 vs untreated 64 +/- 5, p = 0.0002), and peak velocity of early transmitral inflow (cm/sec) increased significantly (treated 96 +/- 7 vs untreated 86 +/- 8, p = 0.0216). The data suggest that troglitazone improves left ventricular diastolic dynamics of a DM rat model at prediabetic stage. PMID- 11205933 TI - Acral necrosis of the fingers as initial manifestation of cutaneous polyarteritis nodosa--a case report. AB - Cutaneous polyarteritis nodosa (CPN) is a well-known entity showing subcutaneous tender nodules, livedo reticularis, and ulcerations as predominant features; arthralgia, myalgia, peripheral neuropathy, and general symptoms such as fever and malaise may also be present. Although the localization of the disease is not specific, the characteristic primary lesions are painful subcutaneous nodules on the lower extremities. Here we report the case of a 33-year-old man with blue colored distal phalanges and necrosis of several fingertips on both hands as the initial manifestation of CPN. PMID- 11205934 TI - Idiopathic bilateral external jugular vein thrombosis--a case report. AB - The authors report a patient with the rare presentation of bilateral external jugular vein thrombosis. A 45-year-old man presented with swelling over both sides of the neck and puffiness of the face. Physical examination revealed cordlike thickening of both the external jugular veins. Two-dimensional echocardiographic and Doppler studies showed thrombosis of both the external jugular veins and digital subtraction angiography (DSA) revealed nonvisualization of external jugular veins of either side. No malignancy, coagulation disorder, or any infection was demonstrable. A regular follow-up for 1 year was done, but no other cause could be found and there was no progression of the disease. PMID- 11205935 TI - Lower extremity strength deficits in peripheral arterial occlusive disease patients with intermittent claudication. AB - The purposes of this study were to quantify the degree and distribution of lower extremity weakness in patients with peripheral arterial occlusive disease (PAOD) compared to apparently healthy older patients and to determine if performance of a simple functional measure correlates with lower extremity strength. Older patients (n = 46), 31 with PAOD (mean age = 69.9 years; mean ankle-brachial index = 0.67) and 15 without PAOD (mean age = 62.6 years; mean ankle-brachial index = 1.20), underwent isometric strength testing of hip, knee, and ankle musculature. In patients with PAOD, dorsiflexion strength was 15% lower (p < 0.05) in the more affected limb (55 +/- 4 Newton-meters; mean +/- SE) versus the less affected limb (65 +/- 5 Newton-meters). Overall, the dorsiflexor muscles of the more affected extremity were 22% weaker (p < 0.05) in the PAOD group than in the non-PAOD group (73 +/- 6 Newton-meters). No other significant differences in strength were found between the PAOD and the healthy elderly groups or between the more affected and less affected limbs in the PAOD patients. The time to perform five sequential sit to-stand transfers using an armless chair was 23% greater (p < 0.01) in the PAOD group (13.0 +/- 0.5 s) than in the healthy elderly (10.7 +/- 0.9 s). In the PAOD patients, dorsiflexor strength was correlated with chair stand time (r = -0.37, p < 0.05). The authors conclude that PAOD patients with intermittent claudication are functionally limited by dorsiflexion weakness, impairing their ability to perform tasks requiring distal lower extremity strength. PMID- 11205936 TI - Left ventricular septal aneurysm in association with bicuspid aortic valve--a case report. AB - Diverticula of the left ventricle are rare cardiac anomalies. Most cases arise from the apex of the left ventricle and are usually found in children. Only a few cases have been documented in adults. The authors report a case of a 38-year-old woman who presented with dyspnea and chest pain. She was found to have a septal left ventricular diverticulum associated with bicuspid aortic valve, aortic stenosis, and aortic regurgitation. The aortic valve was replaced with the resection of the diverticulum. Pathologic examination confirmed the diagnosis of fibrous diverticulum. PMID- 11205937 TI - A huge mitral valve tumor and its vascularity--a case report. AB - Primary cardiac tumors of the mitral valve are extremely rare; however, they present a major risk of embolization. Therefore, prompt diagnosis and urgent treatment is obligatory. The authors report the case of a 60-year-old man with a huge mitral valve mass and its vascularity, which was diagnosed by transthoracic echocardiography and selective coronary arteriography. Our patient's mitral valve tumor had a size of 5.9 x 2.9 cm, which was the largest size reported up to this time in this location. The patient died from a major cerebrovascular event before surgical excision could be performed. PMID- 11205939 TI - Absence of left anterior descending artery associated with atherosclerotic heart disease. PMID- 11205938 TI - Myocardial infarction during sleep deprivation in a patient with dextrocardia--a case report. AB - A patient with dextrocardia who suffered his first myocardial infarction after approximately 26 hours of a diagnostic sleep deprivation protocol is described. The infarction started about 3 hours after a significant improvement in mood, which persisted during and after infarction. Total sleep deprivation may be an acute risk factor for myocardial infarction. PMID- 11205940 TI - The effects of processing methods on the levels of lysine, methionine and the general acceptability of ogi processed using starter cultures. AB - Batches of ogi were produced from maize flour slurry, dehulled maize grains and whole maize grains using Saccharomyces cerevisiae and Lactobacillus brevis as starter cultures. Fermentation over time showed that dehulled maize grains inoculated with the starter cultures and processed whole maize grains requiring steeping led to higher acid production than fermentation with dry-milled maize slurry. Ogi from dehulled maize grains inoculated with starter cultures showed the highest levels of lysine and methionine. Steeping grains encouraged a stronger ogi aroma than fermentation of maize flour slurry alone. Lactobacillus brevis contributed most to the taste of ogi. Fermentation with starter cultures showed good prospects for improving the lysine and methionine levels of ogi. PMID- 11205941 TI - Nisin-producing organisms during traditional 'Fior di latte' cheese-making monitored by multiplex-PCR and PFGE analyses. AB - In this work we studied using different molecular methods the population dynamics of nisin-producing organisms and the persistence of such organisms within a complex ecosystem, 'Fior di latte' cheese, a traditional high-moisture pasta filata cheese. Using the primers targeting the eubacterial 16S-23S rRNA spacer region, together with those amplifying the nisA or nisZ gene, we were able to provide a rapid species identification of the isolates. Inhibitors of Lactococcus lactis subsp. lactis DSM 20481T used as indicator occurred during the whole process of cheese manufacture as a significant part of lactic microflora; however, only 12 among 109 isolates of bacteriocin producers were nisin producers. Amplification of the nisA or nisZ gene, using DNA extracted directly from dairy samples as templates, showed that the nisin structural gene was detected during cheese-making from milk samples up to the end of curd ripening but not in the final cheese. In order to monitor nisin-producing strains during cheese manufacturing, the 12 Lactococcus lactis nis+ strains were analysed by low frequency restriction fragment and PFGE. Nine isolates among the 12 nisin producers exhibited an unique and distinct DNA banding pattern and are considered to be genetically diverse. The other three isolates from curd after ripening showed the same restriction pattern and could be the same strain. In fact, it was also isolated 2 months after the first analysis of cheese-making of 'Fior di latte'. PMID- 11205942 TI - Growth modelling of heat-resistant fungi: the effect of water activity. AB - Growth of three strains of heat-resistant fungi, Byssochlamys fulva, Neosartorya fischeri and Talaromyces avellaneus, was studied at 25 degrees C at eight or nine water activities (a(w)) adjusted with sucrose between 0.995 and 0.85. The flexible growth model of Baranyi describing the change in colony diameter (mm) with respect to time was first fitted to measured growth data and from the fitted curves the maximum colony growth rates were estimated. These values were fitted with respect to a(w) to predict colony growth rates at any a(w) within the range tested. Optimum a(w) values of 0.986, 0.985, and 0.990 for growth, and maximum colony growth rates of 12.6, 13.2 and 20.2 mm d(-1), respectively, were calculated. The time to reach a colony diameter of 3 mm and the optimum a(w) for each strain were also calculated. The results can be applied to the prevention of spoilage of canned fruit or juices and other heat processed fruit based products. PMID- 11205943 TI - The effect of calcium and sodium lactates on growth from spores of Bacillus cereus and Clostridium perfringens in a 'sous-vide' beef goulash under temperature abuse. AB - The effect of calcium and sodium lactates on growth from spores of Bacillus cereus and Clostridium perfringens at three different concentrations (0, 1.5 and 3% w/w) and at different temperatures (10, 15 and 20 degrees C for B. cereus and 15, 20 and 25 degrees C for C. perfringens) was investigated, using beef goulash as a model system for pasteurised vacuum-packaged convenience foods. Calcium lactate at a level of 3% reduced the pH values of the samples from 6.0 to 5.5. No B. cereus growth was observed at 10 degrees C, but after 7 days at an incubation temperature of 15 degrees C, cell number increased by 1 log cfu/g in the control samples. At this temperature, lactates were seen to be effective at inhibiting growth. Calcium lactate was more inhibitory than sodium lactate as the growth of B. cereus was inhibited at 1.5 and 3% concentrations at 20 degrees C, respectively. Growth of C. perfringens was arrested in the presence of 1.5% calcium lactate at all storage temperatures, whereas growth was inhibited by 3% sodium lactate only at 15 degrees C. PMID- 11205944 TI - Heat resistance of Bacillus cereus, Salmonella typhimurium and Lactobacillus delbrueckii in relation to pH and ethanol. AB - The aim of the present work was to investigate the effect of ethanol alone and in combination with low pH on the heat resistance of specific bacteria. The bacteria chosen are representative of heat resistant and heat sensitive pathogens (Bacillus cereus and Salmonella typhimurium) and of relatively heat resistant spoilage microorganisms (Lactobacillus delbrueckii). The chosen bacteria were treated at different temperatures ranging between 70 and 97 degrees C for B. cereus, 48 and 54 degrees C for S. typhimurium and 44 and 60 degrees C for L. delbrueckii, in media of different pH (3, 5 and 7) and ethanol content (0, 2.5, 5, 7.5 and 10%). Both factors proved to be very effective in reducing the heat resistance of the bacteria examined in this work. At pH 7, an increase in ethanol content up to 10% caused D values to decrease by up to 100-fold (S. typhimurium). A drop from pH 7 to pH 3 also caused up to a 100-fold reduction in the D values (S. typhimurium). For B. cereus the regression analysis of the log10 of the D value in relation to temperature, pH and ethanol content was used to produce a second order polynomial equation. The z values increased at decreasing pH and cells were more sensitive to ethanol at lower pH. For S. typhimurium the polynomial equation produced to describe the relationship between log10 of the D values and temperature and ethanol content was also a second order equation indicating that the relationship between z values and ethanol was non-linear. For L. delbrueckii, z values were independent of the ethanol content of the heating medium. Acid tolerance at 25 and 37 degrees C (L. delbrueckii and S. typhimurium) and acid adaptation (S. typhimurium) were also tested. L. delbrueckii was more ethanol and pH tolerant than S. typhimurium at heat treatment temperatures whilst S. typhimurium was more acid tolerant than L. delbrueckii at incubation temperatures (25 and 37 degrees C). Acid adaptation increased the tolerance of S. typhimurium to low pH at 25 degrees C but failed to improve its thermal resistance at 48 degrees C. In all bacteria used, the effects of pH and ethanol were more evident at lower treatment temperatures and therefore their significance becomes greater in view of reduced thermal processing and/or changes in product formulation. PMID- 11205945 TI - Factors influencing resuscitation and growth of heat injured Listeria monocytogenes 13-249 in sous vide cooked beef. AB - The growth of Listeria monocytogenes 13-249 in vacuum-packed, minced beef was investigated as a function of degree of heat injury (including no injury i.e. uncooked beef), growth phase (logarithmic and late stationary phase), pH (5.6 and 6.2), and storage temperature (3, 10 and 20 degrees C) during a storage period of 30 days. Late logarithmic and late stationary phase cultures of L. monocytogenes 13-249 showed similar growth in refrigerated, vacuum-packed, raw minced beef with a high pH (6.2). In normal pH (5.6) beef there was no growth at 3 degrees C while growth at 10 and 20 degrees C was only observed for logarithmic phase cultures. Heat injured late stationary phase cultures with 95-99.9% injured cells in the surviving population (as measured by differential plating on enriched vs. selective media after sous vide cooking) did not grow or repair sublethal injuries in sous vide cooked beef at 3 degrees C while repair and growth took place at 10 as well as at 20 degrees C. In logarithmic phase cultures heat injury occurred very rapidly and > or = 99.9% heat injury was observed in all trials in spite of much lower pasteurization values and fewer log10 reductions compared with late stationary phase cultures. Regardless of growth phase, all cultures where a high degree of heat injury (> or = 99.9%) was observed, did not subsequently grow in the beef product at 3 or 10 degrees C within 30 days. Growth of heat injured cultures preexposed to heat shock (46 degrees C, 30 min) or slowly rising temperatures (0.3 degrees C min(-1)) before heat injury was also investigated. Heat shocked or heat adapted cultures generally responded in the same manner as non-stressed cultures (no growth at 3 degrees C) except that a longer lag phase was observed in beef processed at slowly rising temperatures and in normal pH beef at 10 degrees C. Although processing at slowly rising temperatures may slightly increase the survival of L. monocytogenes 13-249 in cooked beef, there seem to be no indication of an increase in subsequent growth potential of the surviving cells. PMID- 11205946 TI - Identification of lactic acid bacteria constituting the predominating microflora in an acid-fermented condiment (tempoyak) popular in Malaysia. AB - Tempoyak is a traditional Malaysian fermented condiment made from the pulp of the durian fruit (Durio zibethinus). Salt is sometime added to proceed fermentation at ambient temperature. In various samples obtained from night markets, lactic acid bacteria (LAB) were the predominant microorganisms, ranging from log 8.4 to log 9.2 cfu g(-1). No other microorganisms were present to such a level. These samples contained reduced amount of saccharose, glucose and fructose but increased amount of D- and L-lactic acid and acetic acid compared with samples of non-fermented durian fruit. Sixty-four isolates of LAB were divided into five groups by use of a few phenotypic tests. A total of 38 strains of LAB were selected for comparison by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of their whole cell protein patterns with a SDS-PAGE database of LAB. These strains were also examined for their carbohydrate fermentation patterns by use of API 50 CH. Isolates belonging to the Lactobacillus plantarum group were shown to be the predominant members of the LAB flora. In addition, isolates belonging to the Lactobacillus brevis group, Leuconostoc mesenteroides, Lactobacillus mali, Lactobacilus fermentum and an unidentified Lactobacillus sp. were also observed. A high degree of diversity among isolates belonging to the Lb. plantarum group was demonstrated by analysis of their plasmid profiles. PMID- 11205947 TI - Evaluation of lysine and methionine production in some Lactobacilli and yeasts from ogi. AB - Lysine and methionine producing cultures of Lactobacillus and yeasts in batch fermentation of ogi were selected by growth in the presence of the analogues, S-2 aminoethyl]-L-cysteine (thialysine) and ethionine respectively. The study shows that 42.5% of the Lactobacillus and 83.3% of the yeast isolates tested were capable of lysine production while 25.0% of the Lactobacillus and 87.8% of the yeast isolates produced methionine. The lysine and methionine yields of Lactobacillus were significantly (P <0.01) higher than that of yeasts. The majority of the yeast isolates excreted most of the lysine and methionine produced. More lysine was produced than methionine in all tested isolates. PMID- 11205948 TI - Salmonella serotypes isolated from turkey meat in Albania. AB - Eleven (11) Salmonella strains were recovered from 11 (8.2%) out of 134 turkey meat samples in Albania, for the period of time 1996-1998. The percentage of Salmonella positive turkey meat samples varied with 5% in 1996 (3 out of 60), 14.7% in 1997 (5 out of 34) and 7.5% in 1998 (3 out of 40). The isolated strains were found to belong to 3 different Salmonella serogroups; 6 isolates to serogroup B, 4 isolates to serogroup D and 1 isolate to serogroup C. Five (5) different serotypes were encountered; Salmonella enteritidis (4 isolates), Salmonella agona (3 isolates), S. saint-paul, S. reading and S. blockley with only one isolate each. One Salmonella strain, belonging to serogroup B, was not completely serotyped. PMID- 11205949 TI - The occurrence of Aeromonas spp. in natural mineral water and well water. AB - The presence of motile Aeromonas spp. in natural mineral water (NMW) and drinking well water in the area of Lecce (Italy) was investigated. Aeromonas spp. were not detected in any of the 60 NMW samples either by the direct and enrichment method. From a total of 20 wells, five were found to contain Aeromonas species with cell number ranging from 26 to 1609 250 ml(-1). In two wells the presence of Aeromonas spp. was not associated to the presence of faecal indicators, i.e. coliforms and faecal coliforms. Sixty-five Aeromonas spp. strains isolated in this survey were identified at species level and some were examined for haemolysis, Voges Proskauer reaction, lysine decarboxylase and sorbitol fermentation, tests which had been previously shown to correlate with production of enterotoxin/cytotoxin. Isolates identified as A. hydrophila and A. sobria showed potentially virulent properties. PMID- 11205950 TI - Membrane damage and enzyme inactivation of Lactobacillus plantarum by high pressure CO2 treatment. AB - Physiological changes of Lactobacillus plantarum (KFRI 815) by high pressure CO2 treatment were investigated to examine the relevance to microbial inactivation. Characteristic properties of the cells measured in this study included salt tolerance, release of UV-absorbing substances, Mg and K ions, proton permeability, glycolysis, H+-ATPase and constitutive enzymes, and dye uptake. The cells treated with high pressure CO2 of 7 MPa at 30 degrees C for 10 min showed the irreversible cellular membrane damages including loss of salt tolerance, leakage of UV-absorbing substances, release of intracellular ions, collapse of proton permeability and uptake of Phloxine B dye. L. plantarum cells after CO2 treatment also exhibited reduced glycolytic activity and inactivation of some constituent enzymes. However, H+-ATPase of the cell membrane maintained its initial specific activity of about 2.50 U/mg protein even though viability of the cells was reduced by several log cycles after high pressure CO2 treatment. PMID- 11205951 TI - Modelling the influence of pH and organic acid types on thermal inactivation of Bacillus cereus spores. AB - A model is proposed to describe the influence pH on the heat resistance of Bacillus cereus spores. In addition to the conventional z value, the effect of pH on the thermal resistance of spores is characterised by a z(pH) value (z(pH) is the distance of pH from a reference pH*, which leads to a 10-fold reduction of D value). The type of organic acid used for acidifying the heating medium, influences the z(pH) value. For nine organic acids, a linear relationship between the calculated z(pH) value and its lower acid pKa is observed. This relationship showed that the acid form (dissociated or undissociated) modifies the thermal spore resistance in addition to the H+ ion. The influence of acetic acid concentration on the D value at pH 7 shows the protective effect of the dissociated acid form on the heat resistance of spores. The acid concentration in the medium modified the heat resistance of spore and the z(pH) value. PMID- 11205952 TI - Investigation of bacterial spore structure by high resolution solid-state nuclear magnetic resonance spectroscopy and transmission electron microscopy. AB - High resolution solid-state nuclear magnetic resonance spectroscopy (NMR) in combination with transmission electron microscopy (TEM) of spores of Bacillus cereus, an outer coatless mutant B. subtilis 322, an inner coatless mutant B. subtilis 325 and of germinated spores of B. subtilis CMCC 604 were carried out. Structural differences in the coats, mainly protein of spores were reflected by NMR spectra which indicated also differences in molecular mobility of carbohydrates which was partially attributed to the cortex. Dipicolinic acid (DPA) of spores of B. cereus displayed a high degree of solid state order and may be crystalline. Heat activation was studied on spores of B. subtilis 357 lux + and revealed a structural change when analysed by TEM but this was not associated with increases in molecular mobility since no effects were measured by NMR. PMID- 11205953 TI - Effect of pH on the heat resistance of spores comparison of two models. AB - All published models describing the effect of pH on the heat resistance of spores can be regarded either as a linear first degree equation or a linear second degree equation. This work aimed to compare both models from three sets of published data for, Clostridium sporogenes and Bacillus stearothermophilus, respectively. The relative quality of fit of each model with respect to the other depends on the species, the strain and the heating temperature. Parameter estimation was more reliable for the second degree model than for of the simple first degree equation. However, in the case of acidic foodstuffs, predictions obtained from the second degree model are more sensitive toward errors of parameter values. The second degree model is better from the point of view of safety at most frequent ranges of pH of foods. Moreover, for Clostridium botulinum the goodness of fit of this model is clearly higher than that of the first degree equation. If this observation is confirmed by further work, the second degree model in application of standard calculations of heat processes of foods would be preferred. PMID- 11205954 TI - Development and validation of a combined temperature, water activity, pH model for bacterial growth rate of Lactobacillus curvatus. AB - A model was established to predict growth rate as a function of temperature, pH and water activity. The model is based on two, earlier developed models, one for growth rate as a function of temperature and water activity and the other for growth rate as a function of temperature and pH. Based on the assumption that combinatory effects between pH and water activity do not exist, the two models were multiplied to produce one overall model. The overall model was then fitted to data sets measured earlier, and the parameters of the model were determined. A new data set with values for controlling variables outside the range of the earlier developed model was then used to validate the overall model statistically. The model was well able to extrapolate outside the measured data range. Finally, the model was updated with all measured data. No significant changes in the parameters were found. The approach followed underpins the gamma concept, since in the gamma concept it is assumed that the effects of controlling variables can be multiplied, and cardinal parameters are not a function of other variables (temperature, pH, and water activity). PMID- 11205955 TI - A comparative study on the use of flow cytometry and colony forming units for assessment of the antibacterial effect of bacteriocins. AB - Flow cytometry was investigated as a rapid method to determine the antibacterial effect of the bacteriocins nisin, pediocin PA-1, and sakacin A on the indicator organisms Lactobacillus reuteri DSM 12246, Lactobacillus sakei NCFB 2714 and Lactobacillus sakei DSM 20017, respectively. Fluorescence intensities of the cells were measured by flow cytometry upon exposure to bacteriocins after staining with carboxyfluorescein diacetate (cFDA) and were compared to the number of colony forming units (CFU). The fluorescence index (FI) of the bacterial populations decreased when exposed to the bacteriocins. For the different bacteriocins the pattern of decreases in FI and colony forming units differed at equal bacteriostatic concentrations. FI was the most sensitive measure of bacteriocin activity, i.e. the decrease in FI was observed at lower bacteriocin concentrations than decrease in CFU. It was demonstrated that the decrease in FI was caused by rapid leakage of carboxyfluorescein from cells exposed to pediocin. Cells showing severe leakage after pediocin treatment could be detected as CFU when transferred to a rich medium. Such a repair was less pronounced for cells exposed to sakacin and very limited for cells exposed to nisin. The influence of temperature and NaCl in combination with pediocin on FI and CFU of Lactobacillus sakei NCFB 2714 was examined at conditions relevant to foods. At all temperatures (5, 10, 20 and 37 degrees C) and NaCl concentrations (0, 2 and 4% w/v) investigated the flow cytometric measurements were significantly more sensitive compared to CFU. Both methods showed that the inhibitory effect of pediocin increased with increasing temperatures and decreased with increasing NaCl concentrations. PMID- 11205956 TI - Interactions between Zygosaccharomyces mellis and Wallemia sebi in diluted molasses. AB - The yeast Zygosaccharomyces mellis and the mould Wallemia sebi were isolated from the same sample of crystalline sugar. Interactions between these fungi were investigated using a diluted molasses medium (water activity 0.89, pH 6.0) as a model system for the syrup film covering the surface of moist crystalline sugar. Single and mixed cultures of Z. mellis and W. sebi were incubated at 25 degrees C for 400 h. Our results show that the growth of Z. mellis in single culture was limited by available glucose and fructose, and that W sebi was able to invert sucrose to glucose and fructose in both single and mixed culture. Furthermore, the presence of W. sebi in the mixed culture increased the maximum specific growth rate of Z. mellis from 0.074 to 0.19 h(-1) and the growth yield of Z. mellis from 7.3 x 10(6) to 5.4 x 10(7) cfu/ml. These results indicate that the ability of W. sebi to invert sucrose may stimulate the growth of Z. mellis. Finally, the presence of Z. mellis inhibited the ability of W. sebi to invert sucrose: W. sebi was able to invert 1.0 g sucrose/l per h in single culture but only 0.6 g sucrose/l per h in mixed culture. As predicted by Raoults law, this corresponded to a reduction in the water activity of the growth medium from 0.890 to 0.850 in single culture, and to 0.865 in mixed culture. PMID- 11205957 TI - Potential probiotic lactic acid bacteria Lactobacillus rhamnosus (HN001), Lactobacillus acidophilus (HN017) and Bifidobacterium lactis (HN019) do not degrade gastric mucin in vitro. AB - The mucus layer (mucin) coating the surface of the gastrointestinal tract (GIT) plays an important role in the mucosal barrier system. Any damage or disturbance of this mucin layer will compromise the host's mucosal defence function. In the present study, the ability of three potential probiotic lactic acid bacteria (LAB) strains (Lactobacillus rhamnosus HN001, Lactobacillus acidophilus HN017, Bifidobacterium lactis HN019) to degrade mucin in vitro was evaluated, in order to assess their potential pathogenicity and local toxicity. The LAB strains were incubated in medium containing hog gastric mucin (HGM, 0.3%) at 37 degrees C for 48 h, following which any decrease in carbohydrate and protein concentration in the ethanol-precipitated portion of the culture medium was determined, using phenol-sulphuric acid and bicinchonic acid (BCA) protein assays, respectively. The change in molecular weight of mucin glycoproteins, following incubation with the test strains, was monitored by SDS-polyacrylamide gel electrophoresis (SDS PAGE). In order to expose any ability of the test strains to degrade mucin visually and more directly, the test strains were also cultured on agarose containing 0.3% HGM and incubated anaerobically for 72 h at 37 degrees C. No significant change in the carbohydrate or protein concentration in mucin substrates was found following incubation with the test strains. No mucin fragments were derived from the mucin suspension incubated with test strains, and no mucinolysis zone was identified on agarose. These results demonstrate that the potential probiotic LAB strains tested here were unable to degrade gastrointestinal mucin in vitro, which suggests that these novel probiotic candidates are likely to be non-invasive and non-toxic at the mucosal interface. PMID- 11205958 TI - High incidence of Listeria monocytogenes in European red smear cheese. AB - The incidence of Listeria and Listeria monocytogenes in European red smear cheese was determined in order to assess whether the lack of recent outbreaks of listeriosis associated with cheese is due to improved hygenic conditions in the dairies. Out of European red-smear cheese samples of various types, 15.8% contained organisms of the genus Listeria, 6.4% of the samples were contaminated with L. monocytogenes, 10.6% with L. innocua, and 1.2% with L. seeligeri. Six cheese samples contained two or more Listeria species, including at least one L. monocytogenes isolate. The incidences of L. monocytogenes in cheeses from various countries were: Italy 17.4%, Germany 9.2%, Austria 10%, and France 3.3%. Listeria were found most frequently in soft and semi-soft cheese. Eight samples contained more than 100 L. monocytogenes cfu/cm2 cheese surface, 2 samples had counts above 10(4) cfu/cm2 cheese surface. Surprisingly, a higher incidence of L. monocytogenes was observed in cheeses made from pasteurized milk (8.0%) than in cheeses manufactured from raw milk (4.8%). Phage-typing of isolated Listeria strains clearly confirmed that (i) contaminations within dairy plants were persistent over a period of several weeks to months and (ii) that cross contamination within the dairy plant is and important factor. Comparison of our data with past surveys seems to indicate that contamination of red smear soft cheese with L. monocytogenes has not decreased sufficiently over the past 15 years. It is therefore strongly recommended that these products are monitored carefully by cheese-making companies. PMID- 11205959 TI - Influence of holding temperature on the growth and survival of Salmonella spp. and Staphylococcus aureus and the production of staphylococcal enterotoxin in egg products. AB - In this study, growth and survival of Salmonella spp. and Staphylococcus aureus in steamed egg and scrambled egg held at 5, 18, 22, 37, 55 and 60 degrees C are investigated. The production of staphylococcal enterotoxin in steamed egg is also examined. Results reveal that Salmonella spp. and Staph. aureus in the egg products multiply best at 37 degrees C, followed closely by 22 and 18 degrees C. Neither pathogen showed growth in the egg products held at 5 degrees C. Initial inoculation dose, holding temperature and holding time affected the population of both organisms found in the egg products. Staphylococcal enterotoxin A (SEA) and B (SEB) are detected only in the egg products held at 37 or 22 degrees C. After holding at 37 degrees C for 36 h, scrambled egg inoculated with ca. 5.0 log cfu/g Staph. aureus contains the highest levels of SEA (> 64 ng/g) and SEB (> 64 ng/g). Although Salmonella spp. and Staph. aureus grow better in steamed eggs than in scrambled eggs, production of staphylococcal enterotoxin, in general, was higher in scrambled eggs than in steamed eggs. On the other hand, a repaid destruction of the test organisms in steamed eggs held at 60 degrees C was observed. Holding the steamed eggs at 60 degrees C, Salmonella spp. and Staph. aureus with an initial population of ca. 5.9 and 5.6 log cfu/g, respectively, reduced to a non detectable level in 1 h. PMID- 11205960 TI - Regular exercise enhances blood pressure lowering effect of acetylcholine by increased contribution of nitric oxide. AB - This study is aimed to test the hypothesis, that short-term daily bouts of exercise alter the endothelial regulation of peripheral vascular resistance by nitric oxide. Rats ran on a treadmill once a day, 5 days a week, for an average of three weeks with gradually increasing intensity (EX), while a control group remained sedentary (SED). Dose dependent reductions in mean arterial blood pressure (resting MABP; SED: 120.0 +/- 3.4 and EX: 127.8 +/- 4.0 mm Hg) of pentobarbital anesthetized rats to intravenous endothelium independent dilator sodium nitropmsside (SNP; 0.6-3.0 microg/kg) were not different in EX and SED animals. In contrast, dose dependent reductions in MABP to endothelium dependent dilator acetylcholine (ACh) were significantly enhanced in EX compared to those in SED rats (at 0.5 and 1.0 microg/kg ACh: 60.3 +/- 2.4 and 66.5 +/- 1.8 vs 52.8 +/- 2.0 and 59.8 +/- 1.7 mmHg, respectively, p<0.01). There was no significant difference in the heart rate (HR) response to ACh and SNP in the two groups of rats. Intravenous administration of 20 mg/kg Nomega-nitro-L-arginine (L-NNA, a nitric oxide synthase inhibitor) elicited a similar increase (approximately 30%) in the MABP in the two groups and eliminated the difference between ACh-induced blood pressure lowering responses in EX and SED rats (at 0.5 and 1.0 microg/kg ACh: 44.6 +/- 4.7 and 56.3 +/- 4.4 vs 50.9 +/- 4.5 and 59.4 +/- 3.6 mm Hg, respectively). Thus, we suggest that the enhanced acetylcholine-induced decrease in systemic blood pressure following regular daily exercise is primarily due to the augmented synthesis of nitric oxide in the endothelium of peripheral vasculature. This change in the function of endothelium could be important in the adaptation of circulation to exercise training. PMID- 11205961 TI - A study of the liver glucocorticoid receptor binding capacity in newborn rat. AB - The binding capacity of newborn and adult rat liver glucocorticoid receptors was compared, using receptor kinetic analysis. Neonatal receptors have (non significantly) lower affinity and significantly less density to dexamethasone than adult ones. However, the neonatal binding is specific and there is no qualitative difference from the adult one. PMID- 11205962 TI - Effects of extracellular pH on the response of the isolated rat mesenteric artery to electrical field stimulation. AB - In experiments on isolated segments of the rat mesenteric artery, effects of changes in solution pH on the response of the segments to noradrenaline (10 microM) or electrical field stimulation (EFS) were studied. The pH 7.8 solution slightly increased (from 0.48 +/- 0.07 mN at pH 7.4 to 0.67 +/- 0.12 mN or by 41%). while the pH 7.0 and 6.6 solutions significantly decreased (to 0.16 +/- 0.05 and 0.08 +/- 0.04 mN or by 66 and 83%, respectively) the EFS-evoked response of the vessel prestretched to the value corresponding to the intravascular pressure of about 100 mm Hg. A pH shift either to the alkaline or acidic range did not change the resting tension (15.65 +/- 0.74 mN at pH 7.4) of the vessel without precontraction. The pH 6.6 solution reduced the response to noradrenaline twofold. Dilation produced by EFS of noradrenaline-precontracted segment was inhibited and the constrictor responses appeared in the pH 6.6 solution. In the vessel pretreated with N(G)-nitro-L-arginine (100 microM), the acidification of the solution (pH 6.6) inhibited the response of the vascular segment to EFS to a lower extent and did not change its response to noradrenaline. The data obtained demonstrate an inhibitory effect of acidosis on reactivity of the rat mesenteric artery as well as a modification of this effect under a high initial tone of the vessel studied. PMID- 11205963 TI - Correlation between ACE activity and mean blood pressure in Iranian normotensive subjects after oral administration of a single dose of enalapril. AB - Relationship between serum ACE activity and mean blood pressure (MAP) after administration of a single oral dose of the ACE inhibitor enalapril 10 and 20 mg tablets was investigated in 19 Iranian normotensive male subjects. Enalapril at doses, which maximally inhibit ACE activity, reduced MAP dose dependently. The t(max) of ACE inhibition decreased significantly by increasing the enalapril doses, but t(max) of MAP reduction did not change by increasing the dose. The AUC (area under the curve) of ACE inhibition versus time was significantly larger in 20 mg enalapril group compare to 10mg enalapril group (p<0.001). A significant correlation was found between log of residual ACE activity and MAP (r=0.4927; p<0.001). It is concluded that in Iranian normal subjects, after administration of a single oral dose of enalapril, MAP related to residual ACE activity. PMID- 11205964 TI - The effect of the glucocorticoid Oradexon on endotoxin-induced peritoneal cell response. AB - Glucocorticoids are important modulators of immune reactions. They are capable of antagonising several effects of the bacterial endotoxin by inhibiting endotoxin induced leukocyte activation, and the production of cytokines and inflammatory mediators. We earlier demonstrated that the antiglucocorticoid RU 38486 enhances the cytokine production induced by endotoxin and aggravates the course of experimental endotoxic and septic shock. In the present study we investigated the effect of the glucocorticoid Oradexon on the endotoxin-induced peritoneal cell response. For measurement of the peritoneal cell response, male CFLP mice (20-25 g) were injected i.p. with 10 microg/10 g body weight endotoxin (E. coli 026:B6 LPS, Difco Lab, Detroit, lot 110273JB). Dexamethasone (Oradexon, N.V, Organon Oss, The Netherlands) was administered i.p., i.v. or s.c. in a dose of 0.1 mg/10 g body weight, alone or concomitantly with endotoxin. We found that bacterial endotoxin increased the total cell count due to neutrophilia at 24 hours and, due to increases in the number of macrophages and lymphocytes 48 and 72 hours after treatment, respectively. The i.p., i.v., and s.c. injection of Oradexon, increased the total cell count and the macrophage count at 24, 48 and 72 hours. The i.p., s.c. and i.v. injection of Oradexon, concomitantly with endotoxin, reduced the total cell count at 48 and 72 hours, due to decreases in the macrophage count. The i.p., i.v. or s.c. administration of Oradexon concomitantly with LPS decreased the lymphocyte count and the neutrophil count at 24 and 72 hours. These results prove that glucocorticoids are capable of modifying the immune cell reactions induced by endotoxin. PMID- 11205965 TI - Strain differences in rabbit adrenocortical structure and morphological evidence of corticomedullary communication. AB - Interstrain differences in the structure of the mouse and rat adrenal cortex are well known, but related data on rabbits are not available. This study was planned to demonstrate possible strain differences in rabbit adrenal morphology and morphological evidence of a communication between cortex and medulla. For this purpose, the zonation of the adrenal cortex of intact mature male and female rabbits of different strains (New Zealand, Chinchilla and California) were compared using morphometry and the corticomedullary junction was evaluated for close relationship. Marked intersex and interstrain differences were found in the adrenocortical zonation. Female rabbits had larger adrenocortical zones than corresponding males. The rabbits of Chinchilla and California strains had the largest cortical sizes. This difference depended largely upon the higher thickness of the zona fasciculata. Whereas, there were no significant strain differences in the thickness of zona glomerulosa and zona reticularis. Furthermore, examination of corticomedullary junction showed that cortex and medulla were interwoven. Single and small accumulations of cortical cells were spread throughout the medulla. Our morphological data showed the presence of significant interstrain differences in the adrenocortical zonation in the rabbits and provide evidence for a possible paracrine interaction between medullary and cortical cells. PMID- 11205966 TI - Effect of glibenclamide and glimepiride treatment on the development of myocardial infarction in rats. AB - The effect of glibenclamide and glimepiride, two orally active antidiabetic sulphonylurea derivatives, on the development of myocardial infarction has been compared. Permanent coronary artery ligation was induced in rats and the development of infarction was evaluated by a computer-assisted method after nitroblue-terazolium staining. Seven-day coronary ligation produced enlargement of the left ventricular cavity, scar thinning and thickening of the non-infarcted myocardium. Glibenclamide treatment (5 mg/kg b.i.d. intraperitoneally) decreased the infarct volume (29.1 +/- 3.5% vs. 39.1 +/- 3.2% in controls), that occurred primarily as a result of more significant thinning of the scar tissue (1.6 +/- 0.04 mm vs. 2.0 +/- 0.13 mm in controls). Glibenclamide also inhibited the thickening of the non-infarcted ventricular septum (2.1 +/- 0.10 mm vs. 2.9 +/- 0.10 mm in controls). In contrast to the effects of glibenclamide, glimepiride treatment (5 mg/kg b.i.d. intraperitoneally) inhibited the enlargement of the left ventricular cavity (15.2 +/- 1.1% vs. 19.9 +/- 1.2% of the left ventricular volume in controls), it did not precipitate scar thinning and did not influence the development of hypertrophy of the non-infarcted myocardium. These results suggest that glimepiride treatment might inhibit the development of left ventricular dilatation after myocardial infarction. Glibenclamide treatment, however, producing a thinning of the scar tissue may further precipitate morphological changes that can contribute to the development of heart failure. PMID- 11205967 TI - Acute effects of zopiclone on blood glucose level and serum lipids in hyperlipidemic rats. Interactions with PK 11195 and flumazenil. AB - Intraperitoneal administration of 5 mg/kg zopiclone a cyclopyrolone acting on the central benzodiazepine receptors was found to produce significant reduction of total lipids, total cholesterol and triglyceride in rats randered hyperlipidemic by intraperitoneal injection of Triton W-1339. Blood glucose level was also reduced. Flumazenil (10 mg/kg) potentiated the hypoglicemic effect of zopiclone but had no additional effect on serum lipids. PK 11195 (25 mg/kg) antagonized the hypolipidemic effects of zopiclone. IN CONCLUSION: 1. The central benzodiazepine receptors are not involved in the hypolipidemic activity of zopiclone. 2. The peripheral type benzodiazepine receptors are partly responsible, for the hypolipidemic activity of this cyclopirrolone. 3. The changes of blood glucose level induced by these drugs does not seem to be related to benzodiazepine receptors. PMID- 11205968 TI - Acute effects of zopiclone on blood glucose level and serum lipids in hyperlipidemic rats. AB - In rats rendered hyperlipidemic by ip administration of Triton WR-1339, the ip administration of zopiclone at doses of 1.25, 2.5, 5.0, 7.5, 10.0 and 15.0 mg/kg, a cyclopyrrolone acting upon the central benzodiazepine receptors, induces very significant reductions of total lipids, total cholesterol, and triglycerides, at nearly all of the doses. The most active dose was 5.0 mg/kg. The blood glucose level was diminished by doses of 1.25, 2.5, 7.5 and 15.0 mg/kg and it was not changed by the rest of the other doses. PMID- 11205969 TI - Accuracy of velocity estimation by Reichardt correlators. AB - Although a great deal of experimental evidence supports the notion of a Reichardt correlator as a mechanism for biological motion detection, the correlator does not signal true image velocity. This study examines the accuracy with which realistic Reichardt correlators can provide velocity estimates in an organism's natural visual environment. The predictable statistics of natural images imply a consistent correspondence between mean correlator response and velocity, allowing the otherwise ambiguous Reichardt correlator to act as a practical velocity estimator. Analysis and simulations suggest that processes commonly found in visual systems, such as prefiltering, response compression, integration, and adaptation, improve the reliability of velocity estimation and expand the range of velocities coded. Experimental recordings confirm our predictions of correlator response to broadband images. PMID- 11205970 TI - Color constancy at a pixel. AB - In computational terms we can solve the color constancy problem if device red, green, and blue sensor responses, or RGB's, for surfaces seen under an unknown illuminant can be mapped to corresponding RGB's under a known reference light. In recent years almost all authors have argued that this three-dimensional problem is too hard. It is argued that because a bright light striking a dark surface results in the same physical spectra as those of a dim light incident on a light surface, the magnitude of RGB's cannot be recovered. Consequently, modern color constancy algorithms attempt only to recover image chromaticities under the reference light: They solve a two-dimensional problem. While significant progress has been made toward achieving chromaticity constancy, recent work has shown that the most advanced algorithms are unable to render chromaticity stable enough so that it can be used as a cue for object recognition [B. V. Funt, K. Bernard, and L. Martin, in Proceedings of the Fifth European Conference on Computer Vision (European Vision Society, Springer-Verlag, Berlin, 1998), Vol. II, p. 445.] We take this reductionist approach a little further and look at the one-dimensional color constancy problem. We ask, Is there a single color coordinate, a function of image chromaticities, for which the color constancy problem can be solved? Our answer is an emphatic yes. We show that there exists a single invariant color coordinate, a function of R, G, and B, that depends only on surface reflectance. Two corollaries follow. First, given an RGB image of a scene viewed under any illuminant, we can trivially synthesize the same gray-scale image (we simply code the invariant coordinate as a gray scale). Second, this result implies that we can solve the one-dimensional color constancy problem at a pixel (in scenes with no color diversity whatsoever). We present experiments that show that invariant gray-scale histograms are a stable feature for object recognition. Indexing on invariant distributions supports almost perfect recognition for a dataset of 11 objects viewed under five colored lights. In contrast, object recognition based on chromaticity histograms (post-color constancy preprocessing) delivers much poorer recognition. PMID- 11205971 TI - Aging of the human lens: changes in lens shape at zero-diopter accommodation. AB - Scheimpflug photographs of the zero-diopter-accommodated anterior segments of 100 human subjects, aged 18 to 70 yr and evenly spaced over this range, were digitized and analyzed to characterize lens and lens nucleus shape as a function of age by the Hough transform and other image analysis methods. Anterior and posterior lens surface curves exhibit a decrease in radius of curvature with increasing age, in qualitative but not quantitative agreement with the earlier observations of Brown [Exp. Eye Res. 19, 175 (1974)]. In contrast, the shape of the lens nuclear boundaries changes little with age. Overall lens volume at zero diopters increases with age, but the volume of the lens nucleus remains unchanged. The lens center of mass moves anteriorly with increasing age, as does the central clear region of the lens. Although these data sets were found to be more variable than those of Brown, the complementary variability of other factors, such as anterior chamber depth, for each subject leads to a very high statistical correlation between lens shape and lens location relative to the cornea. This supports the finding of previous work that image formation on the retina for a given individual results from the multifactorial balancing of related factors. PMID- 11205972 TI - Spatial summation of peripheral Gabor patches. AB - Previous studies have specified the foveal pattern that is seen most efficiently, with the assumption that the waveform of the best pattern matches the impulse response of the most sensitive visual filter. We measured the threshold contrast for circular, collinear, and orthogonal Gabor stimuli of 6 Hz temporal frequency presented 7 deg above the fixation point. We found that the threshold contrast energy is minimal for a class of stimuli whose Fourier-spectra bandwidth is less than approximately 1 octave. These findings suggest that an energy algorithm might underlie spatial summation of peripheral Gabor patches. The different behavior of spatial summation in fovea and periphery might reflect the differences in pattern detectability across space in the central and peripheral visual fields. It is also possible that a coherent (cross-correlation) algorithm is employed in detection of foveal stimuli and that an incoherent (energy) algorithm is employed in detection of peripheral stimuli. PMID- 11205973 TI - Contrast sensitivity function and image discrimination. AB - A previous study tested the validity of simulations of the appearance of a natural image (from different observation distances) generated by using a visual model and contrast sensitivity functions of the individual observers [J. Opt. Soc. Am. A 13, 1131 (1996)]. Deleting image spatial-frequency components that should be undetectable made the simulations indistinguishable from the original images at distances larger than the simulated distance. The simulated observation distance accurately predicted the distance at which the simulated image could be discriminated from the original image. Owing to the 1/f characteristic of natural images' spatial spectra, the individual contrast sensitivity functions (CSF's) used in the simulations of the previous study were actually tested only over a narrow range of retinal spatial frequencies. To test the CSF's over a wide range of frequencies, the same simulations and testing procedure were applied to five contrast versions of the images (10-300%). This provides a stronger test of the model, of the simulations, and specifically of the CSF's used. The relevant CSF for a discrimination task was found to be obtained by using 1-octave Gabor stimuli measured in a contrast detection task. The relevant CSF data had to be measured over a range of observation distances, owing to limitations of the displays. PMID- 11205974 TI - Discrimination of wide-field images as a test of a peripheral-vision model. AB - In order to test a model of peripheral vision, various contrast sensitivity functions (CSF's) and fundamental eccentricity constants (FEC's) [see J. Opt. Soc. Am. A 8, 1762 (1991)] were applied to real-world, wide-field (6.4 degrees-32 degrees eccentricity) images. The FEC is used to model the change in contrast sensitivity as a function of retinal eccentricity. The processed test images were tested perceptually by determining the threshold FEC for which the observers could discriminate the test images from the original image. It was expected that higher CSF sensitivity would be associated with higher FEC's; and in fact, for images processed with low-pass (variable-window stimuli) CSF's, the threshold FEC's were larger for the higher-sensitivity (pattern-detection) CSF than for the lower-sensitivity (orientation detection) CSF. When two higher-sensitivity CSF's were compared, the bandpass (constant-window stimuli) CSF resulted in essentially the same FEC threshold as did the low-pass (variable-window stimuli) CSF. The fact that the FEC compensated for complex differences in the form of the CSF suggested that the discrimination task was mediated by a limited range of spatial frequencies over which the two CSF's were similar. Image contrast was then varied in order to extend the range of spatial frequencies tested. The FEC's estimated with the lower-contrast test images were unchanged for test images obtained with the high-sensitivity, bandpass CSF but increased for test images obtained with the high-sensitivity, low-pass CSF. These results suggest that peripheral contrast sensitivity as used in the present discrimination task is based on a high-sensitivity, bandpass CSF. The peripheral-vision model validated by the present analysis has practical applications in the evaluation of wide-field simulator images as well as area-of-interest or other foveating systems. PMID- 11205975 TI - Appearance of images through a multifocal intraocular lens. AB - The appearance of images through a multifocal intraocular lens (IOL) was simulated. The optical transfer function (OTF) of a model eye containing the multifocal lens was measured and divided by the OTF of the model eye with a monofocal IOL. This ratio was used to filter digital images, generating simulations that represent the retinal images seen through a multifocal intraocular lens when viewed through an eye with a monofocal lens. A dichoptic side-by-side display was used to present the original image to one eye, implanted with the multifocal lens, while the other eye, implanted with monofocal lens, viewed the simulations and variations on the simulations to derive a point of subjective equivalence. Four subjects with such bilateral lens implants were tested for near and distance vision. The results validate the test methodology and the simulations. Referenced to the nominal theoretical filter, the prediction was within a 0.25-diopter (D) blur for distance simulation and within a 0.50-D blur for the near-vision simulation. PMID- 11205977 TI - Spatiotemporal digital microholography. AB - We develop the theoretical background of a holographic method in which the hologram is sampled simultaneously in space and in time by a charge-coupled device (CCD) sensor. With the use of temporal heterodyning (rather than spatial heterodyning, which is employed in conventional holography), in-line, single sideband holograms of fields having an arbitrary degree of spatial coherence are recorded in an exposure time that can theoretically be as short as four frames of the CCD. The method is applied to microholography and is shown to avoid the main drawbacks of conventional holographic microscopy, namely, the need for high spatial-bandwidth detectors and for a high degree of spatial coherence, which unavoidably leads to speckle noise. The possibility of a posteriori aberration compensation is demonstrated, and experimental results are presented. PMID- 11205976 TI - Age-related changes in wavelength discrimination. AB - Wavelength discrimination functions (420 to 620-650 nm) were measured for four younger (mean 30.9 years) and four older (mean 72.5 years) observers. Stimuli consisted of individually determined isoluminant monochromatic lights (10 Td) presented in each half of a 2 degrees circular bipartite field with use of a Maxwellian-view optical system. A spatial two-alternative forced-choice method was used in combination with a staircase procedure to determine discrimination thresholds across the spectrum. Small but consistent elevations in discrimination thresholds were found for older compared with younger observers. Because the retinal illuminance of the stimuli was equated across all observers, these age related losses in discrimination are attributable to neural changes. Analyses of these data reveal a significant change in Weber fraction across adulthood for a chromatically opponent pathway receiving primarily antagonistic signals from middle-wavelength-sensitive and long-wavelength-sensitive cones but not for a short-wavelength-sensitive cone pathway. PMID- 11205978 TI - A posteriori processing of spatiotemporal digital microholograms. AB - In an accompanying paper [G. Indebetouw and P. Klysubun, J. Opt. Soc. Am. A 18, 319 (2001)], the theoretical background of a spatiotemporal digital microholographic method was described, and some experimental results were presented. Here the usefulness of the method for microholographic imaging of biological specimens such as cells is demonstrated. The vast possibility of a posteriori processing of the microholograms is discussed. Dark-field, phase contrast, and interference-contrast images, as well as quantitative phase maps, all obtained a posteriori from the same microhologram, are illustrated as examples. PMID- 11205979 TI - Necessary conditions for spatially incoherent illumination of a three-dimensional object. AB - Spatially incoherent imaging systems are characterized by a linear-in-intensity relationship between the object and the image distributions. While strict spatial incoherence is theoretically not achievable, a particular imaging system may be made effectively linear in intensity by a choice of the appropriate illumination source location and size. The requirement for source size for effectively incoherent illumination of a two-dimensional object is well known. I extend the arguments for choosing the source size in a two-dimensional imaging system to develop necessary conditions for the source size for effectively spatially incoherent illumination of a three-dimensional object. While the conditions are necessary, they are not sufficient, since coherence in the direction of the optical axis is not addressed. PMID- 11205980 TI - Two-dimensional phase unwrapping with use of statistical models for cost functions in nonlinear optimization. AB - Interferometric radar techniques often necessitate two-dimensional (2-D) phase unwrapping, defined here as the estimation of unambiguous phase data from a 2-D array known only modulo 2pi rad. We develop a maximum a posteriori probability (MAP) estimation approach for this problem, and we derive an algorithm that approximately maximizes the conditional probability of its phase-unwrapped solution given observable quantities such as wrapped phase, image intensity, and interferogram coherence. Examining topographic and differential interferometry separately, we derive simple, working models for the joint statistics of the estimated and the observed signals. We use generalized, nonlinear cost functions to reflect these probability relationships, and we employ nonlinear network-flow techniques to approximate MAP solutions. We apply our algorithm both to a topographic interferogram exhibiting rough terrain and layover and to a differential interferogram measuring the deformation from a large earthquake. The MAP solutions are complete and are more accurate than those of other tested algorithms. PMID- 11205982 TI - Light scattering and ink penetration effects on tone reproduction. AB - Light scattering, or the so-called Yule-Nielsen effect, and ink penetration into the substrate paper play important roles in tone reproduction. We develop a framework in which the influences of both of these effects on the reflectance and tristimulus values of a halftone sample are investigated. The properties of the paper and the ink and their bilateral interaction can be parameterized by the reflectance Rp(o) of the substrate paper, the transmittance Ti of the ink layer, the parameter gamma describing the ink penetration, and p describing the Yule Nielsen effect. We derive explicit expressions that relate the reflectance of the ink dots (Ri), the paper (Rp) and the halftone image (R) as functions of these parameters. We also describe the optical dot gain as a function of these parameters. We further demonstrate that ink penetration leads to a decrease in optical dot gain and that scattering in the paper results in the printed image's being viewed as more saturated in color. PMID- 11205981 TI - In-depth resolution for a strip source in the Fresnel zone. AB - The problem of determining the achievable resolution limits in the reconstruction of a current distribution is considered. The analysis refers to the one dimensional, scalar case of a rectilinear, bounded electric current distribution when data are collected by measurement of the radiated field over a finite rectilinear observation domain located in the Fresnel zone, orthogonal and centered with respect to the source. The investigation is carried out by means of analytical singular-value decomposition of the radiation operator connecting data and unknown, which is made possible by the introduction of suitable scalar products in both the unknown and data spaces. This strategy permits the use of the results concerning prolate spheroidal wave functions described by B. R. Frieden [Progress in Optics Vol. IX, E. Wolf, ed. (North-Holland, Amsterdam 1971), p. 311.] For values of the space-bandwidth product much larger than 1, the steplike behavior of the singular values reveals that the inverse problem is severely ill posed. This, in turn, makes it mandatory to use regularization to obtain a stable solution and suggests a regularization scheme based on a truncated singular-value decomposition. The task of determining the depth resolving power is accomplished with resort to Rayleigh's criterion, and the effect of the geometrical parameters of the measurement configuration is also discussed. PMID- 11205983 TI - Coherent broadband light effects in grating spectrometer studies of emission from alkali atoms at surfaces. AB - With ordinary grating spectrometers, strong bands that are due to broadband coherent light emission from samples containing various amounts of alkali atoms can be observed. The coherent light is proposed to be emitted by the alkali Rydberg states that are easily formed in these systems. The edges of the bands are observed at angles corresponding to low numbers of standing waves along the grating surface and perpendicular to it. This type of band is observed both with thermal sources and with broadband light sources created by pulsed laser light, and it is observed only with s-polarized (TE-mode) light. The band intensities are independent of the entrance slit width in the spectrometer, which shows that strong interference effects exist. The number of interference fringes observed on top of the most intense band is directly proportional to the width of the entrance slit. The time-resolved signal shows that large photon peaks from thermal sources are emitted in bursts within 2 mus, probably corresponding to the lifetime of the emitting Rydberg states and Rydberg clusters. PMID- 11205984 TI - Scattering by a slab containing randomly located cylinders: comparison between radiative transfer and electromagnetic simulation. AB - This study is devoted to the examination of scattering of waves by a slab containing randomly located cylinders. For the first time to our knowledge, the complete transmission problem has been solved numerically. We have compared the radiative transfer theory with a numerical solution of the wave equation. We discuss the coherent effects, such as forward-scattering dip and backscattering enhancement. It is seen that the radiative transfer equation can be used with great accuracy even for optically thin systems whose geometric thickness is comparable with the wavelength. We have also shown the presence of dependent scattering. PMID- 11205985 TI - Limits of the small-angle approximation to the radiative transport equation. AB - The small-angle approximation to the radiative transport equation is used extensively in imaging models in which the transport medium is optically thick. The small-angle approximation is generally considered valid when the particles are very large compared with the wavelength, when the refractive-index ratio of the particle to the medium is close to 1, and when the optical thickness is not too large. We report results showing the limits of the validity of the small angle approximation as a function of particle size and concentration for a particle-to-medium fixed refractive-index ratio of 1.196. This refractive-index ratio is comparable with that of minerals or diatoms suspended in water. PMID- 11205986 TI - Stable inversion method for a polarized-lidar: analysis and simulation. AB - A new inversion inhomogeneous atmosphere (IA) method that is more stable than Fernald's method for two-component (molecule and aerosol) scattering analysis of polarized Mie lidar signals is proposed and examined. The backscattering coefficient and the extinction-to-backscattering ratio (EBR) can be calculated for specified regions at which the depolarization ratio is less than that of molecule without further assumptions. The inversion procedure can be extended to both inward stepwise and outward stepwise integration algorithms. Simulation results indicate that a higher precision was achieved with the IA method than with Fernald's method in terms of error and random noise in estimating boundary value and EBR. Experimental results were also better with the IA method than with Fernald's method. PMID- 11205987 TI - Improved compensation of turbulence-induced amplitude and phase distortions by means of multiple near-field phase adjustments. AB - An approach for compensation of turbulence-induced amplitude and phase distortions is described. Two deformable mirrors are placed optically conjugate to the collecting aperture and to a finite range from this aperture. Two control algorithms are presented. The first is a sequential generalized projection algorithm (SGPA) that is similar to the Gerchberg-Saxton phase retrieval algorithm. The second is a parallel generalized projection algorithm (PGPA) that introduces constraints that minimize the number of branch points in the control commands for the deformable mirrors. These approaches are compared with the approach of placing the second deformable mirror conjugate to the far field of the collecting aperture and using the Gerchberg-Saxton algorithm to determine the optimal mirror commands. Simulation results show that placing the second deformable mirror at a finite range can achieve near-unity Strehl ratio regardless of the strength of the scintillation induced by propagation through extended paths, while the maximum Strehl ratio of the far-field approach drops off with increasing scintillation. The feasibility of the solutions is evaluated by counting the branch points contained in the deformable mirror commands. There are large numbers of branch points contained in the control commands that are generated by the Gerchberg-Saxton SGPA-based algorithms, irrespective of where the second deformable mirror is located. However, the control commands generated by the PGPA with branch point constraints achieves excellent Strehl ratio and minimizes the number of branch points. PMID- 11205988 TI - Colorimetric and spectroradiometric characteristics of narrow-field-of-view clear skylight in Granada, Spain. AB - As part of our ongoing research into the clear daytime sky's visible structure, we analyze over 1,500 skylight spectra measured during a seven-month period in Granada, Spain. We use spectral radiances measured within 3 degrees fields of view (FOV's) to define colorimetric characteristics along four sky meridians: the solar meridian and three meridians at azimuths of 45 degrees, 90 degrees, and 315 degrees relative to it. The resulting clear-sky chromaticities in 44 different view directions (1) are close to but do not coincide with the CIE daylight locus, (2) form V-shaped meridional chromaticity curves along it (as expected from theory), and (3) have correlated color temperatures (CCT's) ranging from 3,800 K to infinity K. We also routinely observe that sky color and luminance are asymmetric about the solar meridian, usually perceptibly so. A principal components analysis shows that three vectors are required for accurate clear-sky colorimetry, whereas six are needed for spectral analyses. PMID- 11205989 TI - Tilted bilayer membranes as simple transmission quarter-wave retardation plates. AB - A tilted bilayer membrane, which consists of two thin films of transparent optically isotropic materials of different refractive indices, can function as a transmission quarter-wave retarder (QWR) at a high angle of incidence. A specific design using a cryolite-Si membrane in the infrared is presented, and its tolerances to small shifts of wavelength, incidence angle, and film thickness errors are discussed. Some designs provide a dual QWR in transmission and reflection. Such devices provide simple linear-to-circular (and circular-to linear) polarization transformers. Bilayer eighth-wave retarders without diattenuation are also introduced. PMID- 11205990 TI - Detection and analysis of depolarization artifacts in rotating-compensator polarimeters. AB - Absolute constraints, namely, the Schwarz inequality and a complementary expression derived by us, are used to obtain corresponding absolute constraints on the Fourier coefficients of the intensity transmitted through rotating compensator polarimeters and ellipsometers. These expressions allow the investigation of artifacts that result in mixed or apparently mixed polarization states over the cross section of the beam, the averaging time of the detector, or the frequency passband of the dispersing element. Examples include multiple internal reflections or inhomogeneous strain within an element, scattered light, and other types of system and component defects that cannot be accessed by means of polarization-state data alone. We apply these results to our polarizer-sample compensator-analyzer (PSCA) ellipsometer to illustrate capabilities. A simple analytic model is shown to give a quantitative description of depolarization in systems for which the resolution is finite and the retardation varies with wavelength. PMID- 11205991 TI - Photonic bandgap structures in planar waveguides. AB - If a one-dimensional (1D) or two-dimensional (2D) photonic bandgap (PBG) structure is incorporated into a planar optical waveguide, the refractive-index nonuniformity in the direction perpendicular to the waveguide plane responsible for waveguiding may affect its behavior detrimentally. Such influence is demonstrated in the paper by numerical modeling of a deeply etched first-order waveguide Bragg grating. On the basis of physical considerations, a simple condition for the design of 1D and 2D waveguide PBG structures free of this degradation is formulated; it is, in fact the separability condition for the wave equation. Its positive effect is verified by numerical modeling of a modified waveguide Bragg grating that fulfills the separability condition. PMID- 11205992 TI - Vertical-cavity surface-emitting resonances in photonic crystal films. AB - It is shown that thin films of dielectric, etched through with a suitably chosen lattice of holes, can support surface-emitting vertical resonances with very-high cavity Q factors (approximately 10(5) in the case of Al(x)GaAs(1-x) on oxidized AlyGaAs1-y). A Bloch-wave expansion is used to develop a complete vector-field analysis of these resonances and to reveal their underlying physics. Since they do not require multilayer mirrors, such resonators are a practical and simple replacement for conventional vertical-cavity surface-emitting laser structures. Other applications include wavelength-division-multiplexing components and highly sensitive gas detectors. PMID- 11205993 TI - Linear and nonlinear operation of a time-to-space processor. AB - The operational characteristics of a time-to-space processor based on three-wave mixing for instantaneous imaging of ultrafast waveforms are investigated. We assess the effects of various system parameters on the processor's important attributes: time window of operation and signal conversion efficiency. Both linear and nonlinear operation regimes are considered, with use of a Gaussian pulse profile and a Gaussian spatial mode model. This model enables us to define a resolution measure for the processor, which is found to be an important characteristic. When the processor is operated in the linear interaction regime, we find that the conversion efficiency of a temporal signal to a spatial image is inversely proportional to the resolution measure. In the nonlinear interaction regime, nonuniform signal conversion due to fundamental wave depletion gives rise to a phenomenon that can be used to enhanced the imaging operation. We experimentally verify this nonlinear operation. PMID- 11205994 TI - Veterinary epidemiology and decision making. PMID- 11205995 TI - Human health hazards associated with the administration of antimicrobials to slaughter animals. Part II. An assessment of the risks of resistant bacteria in pigs and pork. AB - Risks for the consumer regarding the acquisition of resistant bacteria and/or resistance genes via the consumption of pork are discussed. In general, Salmonella spp. and Escherichia coli that originate from animals do not easily transfer their resistance genes to the resident intestinal flora of humans. The prevalence of resistant E. coli in humans seems more associated with being a vegetarian (odds ratio (OR) 1.89) than with the consumption of meat and meat products. Other risk factors are treatment with antimicrobials (OR 2-5), becoming hospitalized (OR 5.93), or working in a health setting (OR 4.38). In the Netherlands, annually an estimated 45,000 people (0-150,000) become a carrier of resistant E. coli and/or resistance genes that ori ginate from pigs, while an estimated 345,000 persons (175,000-600,000) become a carrier of resistant E. coli and/or resistance genes that originate from hospitals, e.g. other patients. Any problems with resistant Salmonella spp. that stem from pigs are, in fact, an integral part of the total problem of food-borne salmonellosis. Sometimes there are outbreaks of a specific multi-resistant clone of S. typhimurium that causes problems in both farm animals and humans. The probability that in the next 30 years there is no or maximally one outbreak of a specific clone that originates from pig herds is estimated at about 75%. Antimicrobials used as a growth promoter can have a measurable influence on the prevalence of resistant bacteria. The likely chain of events regarding avoparcin and the selection and dissemination of resistance against vancomycin in the enterococci gives the impression that the impact of the use of antimicrobials in animals on the prevalence of resistance in humans is largely determined by whether resistance genes are, or become, located on a self-transferable transposon. Furthermore, consumer health risks of antimicrobials used in slaughter pigs are mainly determined by the selection and dissemination of bacterial resistance and much less by the toxicological properties of any residues in pork. It is also concluded that most of the problems with resistant bacteria in humans are associated with the medical use of antimicrobials, and that the impact of particularly the veterinary use of antimicrobials is limited. However, the impact of antimicrobials used as a feed additive appears to be much greater than that of antimicrobials used for strictly veterinary purposes. The use of antimicrobials as a feed additive should therefore be seriously reconsidered. PMID- 11205996 TI - Human health hazards associated with the administration of antimicrobials to slaughter animals. Part I. An assessment of the risks of residues of tetracyclines in pork. AB - This article describes the assessment of consumer risks of residues of tetracyclines in slaughter pigs in the Netherlands. The assessed risks were toxic and allergic reactions, and the disturbance of the consumers' intestinal flora. Toxic and allergic reactions in humans and animals have only been observed at therapeutic doses, affecting between an estimated 1 in 5,000 and one 1 in 140,000 individuals exposed. Residues of tetracyclines in pigs are closely associated with treatment with injectable formulations. Established Maximum Residue Levels (MRLs) do not reflect actual consumer risks in case a limit is violated incidentally. For example, when the established MRLs for tetracyclines in meat are exceeded with a factor 400, 40,000, and 200,000, respectively, the actual risk of an adverse drug reaction for the consumer following a single consumption of this meat is maximally 1 in 3 million, 1 in 300,000, and 1 in 8,000, respectively. At the current estimated low levels of incidental exposure via pork, the annual risk of negative health effects for a random consumer is estimated at maximally 1 in 33 million. The annual risk that a temporary disturbance of the intestinal flora may also result in a facilitated infection with certain enteropathogens, such as Salmonella spp., is estimated at 1 in 45 million. It is concluded that the current microbiological risks of pork are greater than the risks of residues of tetracyclines as such, and that the control of the microbiological risks of pork should therefore be given first priority. PMID- 11205997 TI - Mathematical modelling of pseudorabies virus (syn. Aujeszky's disease virus) outbreaks aids eradication programmes: a review. AB - Pseudorabies virus will be eradicated from the Netherlands if a typical infectious pig (Rind) infects, on average, less than one other pig. In this review, we used a stochastic SIR model to estimate Rind using data from the field and from experiments. Rind in sow herds was estimated to be significantly less than 1 and in rearing and finishing pigs Rind was higher than 1. However, if Rind is higher than 1, PRV can still be eradicated if one infectious herd infects less than one other herd during the period that the herd is infectious(Rherd <1). Some future developments in Dutch pig husbandry (e.g. group-housing of sows) and possible risks after halting vaccination are also quantitatively evaluated. PMID- 11205998 TI - Review: reticuloruminal motility--a pharmacological target with a difference? AB - The vagal sensory inputs to and motor outputs from the hindbrain gastric centres required for reticuloruminal motility were sampled directly in anaesthetized sheep using electrophysiological 'single fibre' techniques and indirectly in conscious, surgically prepared sheep. Drugs were administered by close-arterial injection into a carotid artery to observe central effects and into the coeliac artery to observe peripheral effects on the reticulorumen. Escherichia coli lipopolysaccharide produced intermediates responsible for the smooth muscle relaxation in the first phase of reticuloruminal stasis and for gastric centre depression in the second phase. Adrenergic influences on reticuloruminal motility comprise (a) an alpha1 adrenoreceptor-induced contracture and raised tension receptor sensitivity, (b) an alpha2 adrenoreceptor-mediated depression of the gastric centres causing stasis, excitation of epithelial receptors evoking rumination, and interference with acetylcholine release in the parasympathetic pathway, (c) abeta1 adrenoreceptor-mediated inhibition of the gastric centres, and (d) abeta2 adrenoreceptor-mediated inhibition of intrinsic and extrinsic motility. PMID- 11205999 TI - Investigation of biochemical and haematological side-effects of cefquinome in healthy dogs. AB - In the present study, the effects of cefquinome, a 4th generation cephalosporin, on clinical, biochemical, haematological, and blood gas variables were investigated. Five healthy dogs were injected with cefquinome (1 mg/kg body weight, IM, daily) for 14 days. Negative effects of cefquinome on clinical, biochemical, and haematological variables were not observed, but it did change some blood gas variables. PMID- 11206000 TI - Macroanatomic investigations of the blood supply of thoracic limb of Kangal dogs. AB - In this study, the arterial supply of the thoracic limb was investigated in Kangal dogs. Twelve adult healthy Kangal dogs of either sex were used. Latex was injected into the common carotid artery, and then the axillary artery was dissected. The axillary artery is a continuation of the subclavian artery and supplies the thoracic limb in Kangal dogs. The axillary artery gave off a deltoid branch and external thoracic, lateral thoracic, and subscapular thoracic arteries in its course along the thoracic wall. The axillary artery continues distally as the brachial artery in the arm. The brachial artery gives rise to the cranial humeral circumflex, deep brachial, bicipital, ulnar collateral, superficial brachial, transverse cubital, and common interosseus arteries. It continues as the median artery after giving off the common interosseus artery. It was observed that the deep antebrachial artery arose from the median artery at the proximal third of the forearm. In the distal third of the forearm, the median artery divided into the palmar carpal and dorsal carpal branches. The deep palmar branch of the radial artery and deep branch of the palmar branch of the caudal interosseus artery form the deep palmar arch. The median artery joined the superficial branch of the palmar branch of the caudal interosseus artery to constitute the superficial palmar arch. The radial artery and cranial interosseus artery contributed to the dorsal carpal rete. The ulnar artery contributed to the formation of the deep and superficial palmar arches. PMID- 11206001 TI - Hyperaldosteronism in a cat with metastasised adrenocortical tumour. AB - In a 12-year-old male shorthaired cat with attacks of hypokalaemic muscular weakness in spite of oral potassium supplementation, highly elevated plasma aldosterone concentrations in combination with low plasma renin activity pointed to primary hyperaldosteronism. Ultrasonography and computed tomography revealed a large left-sided adrenal tumour growing into the phrenicoabdominal vein and the caudal vena cava. The tumour and its intravascular extension were surgically removed, but the subsequent stenosis of the caudal vena cava caused congestion and renal failure. At autopsy pulmonary micrometastases of the aldosteronoma were found. PMID- 11206002 TI - Population parameters to compare dog breeds: differences between five Dutch purebred populations. AB - Differences in five purebred dog populations born in 1994 in the Netherlands were evaluated using different parameters. Numerically, the Golden Retriever was the largest breed (840 litters of 234 sires) and the Kooiker Dog (101 litters of 41 sires) the smallest. The litter per sire ratio was largest in the Bernese Mountain Dog (4.59) and lowest in the Kooiker Dog (2.46). The mean relatedness and the actual mean level of inbreeding in the studied generations were 0.102 and 0.056 respectively for the Bernese Mountain Dog, 0.041 and 0.046 for the Bouvier des Flandres, 0.087 and 0.061 for the Boxer, 0.020 and 0.018 for the Golden Retriever, and 0.146 and 0.070 for the Kooiker Dog. Quantification and visualization of population parameters for purebred dogs will facilitate the comparison of breeds and the comparison of breeds in different periods or countries. It appears unlikely that the increase in inbreeding is a major determinant of the possible increase in the frequency of genetic diseases. PMID- 11206003 TI - Neurological signs in a horse due to metastases of an intestinal adenocarcinoma. AB - A 22-year-old Dutch Warmblood mare was referred to Utrecht University with progressive left hind limb paresis and hyporeflexia. The preliminary clinical diagnosis was the neurological form of equine herpes virus (EHV-1) infection. Within 1 day of admission, the mare became recumbent and deteriorated rapidly. Postmortem examination revealed an adenocarcinoma of the caecum, with metastases in all regional lymph nodes and extending from the lumbar nodes into the vertebral canal, causing spinal cord compression and destruction of the left 4th and 5th lumbar nerves. PMID- 11206004 TI - Cows, cats, and FSE: death penalty justified? AB - Transmissible spongiform encephalopathies affect a number of mammalian species. The most common spongiform encephalopathies are scrapie in sheep and Bovine Spongiform Encephalopathy (BSE) in cattle. Feline Spongiform Encephalopathy (FSE) is a related disorder in domestic cats. Because of the link between BSE and FSE, cats are put on a par with cattle, in terms of politics and regulations. In the Netherlands, when a case of BSE is found on a farm, not only the ruminants, but also the cats are taken away for post-mortem examination. So far, the cats examined have always been negative for FSE. There are no scientific reasons for destroying the cats on farms where BSE has been found. PMID- 11206005 TI - Oncological scintigraphy in dogs with 99mTechnetium MIBI and DMSA(V)--two case reports. AB - Oncological scintigraphy is described in two dogs with malignant lymphoma and malignant schwannoma, respectively. The distribution of the radiopharmaceuticals could be visualized for the purpose of detection of neoplasia and eventual metastases, and to evaluate the effectivity of therapy. It is concluded that 99mTechnetium MIBI and 99mTc DMSA (V) scintigraphy is useful for the detection of soft tissue malignancy in dogs. PMID- 11206006 TI - Expression of multidrug resistance-associated protein (MRP) in human gliomas. AB - Drug resistance is a major clinical problem in the chemotherapy of human gliomas. The multidrug resistance-associated protein (MRP), a membrane transporter related to non-P-glycoprotein multidrug resistance, is overexpressed in some drug selected cancer cell lines. To investigate whether MRP is involved in the intrinsic drug resistance of human gliomas, surgical specimens of 20 gliomas (11 glioblastomas, 6 anaplastic astrocytomas, and 3 astrocytomas), 3 normal brain specimens, and 4 glioma cell lines (U87MG, U251MG, U373MG, and T98G) were analyzed. The expression of MRP was studied by RT-PCR and immunohistochemistry in the surgical specimens. The MRP expression levels in the cell lines were assessed by the quantitative RT-PCR and Western blot analyses. Sensitivity to adriamycin (ADM), etoposide (VP-16), cisplatin (CDDP), and 1-(4-amino-2-methyl-5 pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU), were determined by MTT assay, and antisense treatment was evaluated in the cell lines. The expression of MRP was detected in 9 of 11 glioblastomas and 3 of 6 anaplastic astrocytomas. The quantitative analyses of the cell lines revealed that the MRP mRNA and protein levels were increased 4.5-fold in the T98G cells as compared to U87MG. T98G cells showed the highest resistance to all drugs. Western blot analysis revealed that treatment with the antisense oligonucleotide reduced the level of MRP expression to 25% of the sense oligonucleotide treatment in T98G cells. The sensitivity to ADM, VP-16 and CDDP was significantly increased in the antisense-treated cells as compared with the sense-treated cells. These results suggest that the MRP expression may be related to the intrinsic multidrug resistance in human gliomas. PMID- 11206007 TI - Altered nuclear localization of bax protein in BCNU-resistant glioma cells. AB - To investigate the role of apoptosis suppression in glioma chemotherapy resistance, protein levels and subcellular localization of bcl-2 family members were investigated in 2 pairs of sensitive cell lines and their in vitro generated resistant derivatives. The alkylating agent, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), induced apoptosis in both sensitive cell strains and apoptosis was suppressed in both resistant derivatives. Both resistant cell lines contained altered regulation of a bcl-2 related protein consistent with the suppression of apoptosis. Independent of which bcl-2 family member was dysregulated, resistance was associated with altered regulation in the subcellular localization of bax protein. Following BCNU treatment, bax accumulated in nucleoli and a nuclei containing fraction of sensitive cells but not their resistant derivatives. Nuclear accumulation was an early event in apoptosis induction. These data indicates altered subcellular localization of bax may play a role in resistance. In addition, the association between an early, nucleolar localization of bax and the induction of apoptosis suggests that localization of bax to nucleoli may play a role in apoptosis-induction of glioma cells. PMID- 11206008 TI - Craniotomy under local anesthesia and monitored conscious sedation for the resection of tumors involving eloquent cortex. AB - OBJECTIVE: Resection or even biopsy of an intra-axial mass lesion in close relationship to eloquent cortex carries a major risk of neurological deficit. We have assessed the safety and effectiveness of craniotomy under local anesthesia and monitored conscious sedation for the resection of tumors involving eloquent cortex. METHODS: We have performed a retrospective review of a consecutive series of 157 adult patients who underwent craniotomy under local anesthesia by one surgeon (P.M.B.) at Brigham and Women's Hospital in Boston. All patients had tumors in close proximity to eloquent cortex, including speech, motor, primary sensory, or visual cortex. In most cases the lesion was considered inoperable by the referring surgeon. All resection was verified by post-operative imaging approximately one month after surgery and all cases were reviewed by an independent neurosurgeon (A.D.). RESULTS: In 122 cases, brain mapping was performed to identify eloquent cortex and in the remainder neurological monitoring was maintained during the procedure. Radiological gross total resection was achieved in 57% of patients and greater than 80% resection was achieved in 23%. Thus 4 out of 5 of patients had major resection despite the close relationship of tumor to eloquent cortex. In 13%, less than 80% of tumor was removed because of danger of neurological deficit. In 7% of patients, only a biopsy could be done because of infiltration into eloquent cortex that could only be assessed at surgery. In 76 patients with pre-operative neurological deficits, there was complete resolution of these deficits in 33%, improvement in 32%, no change in 28%, and long-term worsening in 8%. Among 81 patients with no pre operative neurological deficit, 1 patient suffered a major permanent neurological deficit, and 2 developed minor deficits. There was a transient post-operative deficit in one-third of cases, but this had resolved at one month in all but three patients. Monitored conscious sedation was performed without anesthetic complications using midazolam, sufentanyl and fentanyl with or without propofol. Only one case needed to be converted to general anesthesia. Patient satisfaction with the procedure has been good. Operating time and hospital stay were lower than the mean for brain tumor craniotomy at this hospital. CONCLUSIONS: Tumor surgery with conscious sedation is a safe technique that allows maximal resection of lesions in close anatomical relationship to eloquent cortex, with a low risk of new neurological deficit. Only 7% of intrinsic cortical tumors were ineligible for partial or complete resection with this technique. PMID- 11206009 TI - Phase II trial of cystemustine, a new nitrosourea, as treatment of high-grade brain tumors in adults. AB - This study included 39 patients (37 evaluable, of whom 30 patients with recurrent gliomas and 7 patients with gliomas untreated by radiotherapy); they were enrolled into a phase II trial using a new nitrosourea, cystemustine, administrated every 2 weeks at 60 mg/m2 as a 15 min-infusion. Pathology at inclusion was (WHO classification): 14 glioblastomas, 20 grade 3-4 astrocytomas and 3 grade 3 oligodendrogliomas. Four partial responses have been obtained, giving an overall response rate of 10.8%. Four additional patients had a partial response, which for various reasons was not confirmed 4 weeks later; 12 patients had a stable disease for at least 8 weeks, 15 patients had progressive disease. Of the 4 responses, 2 were with a grade 3 oligodendroglioma and 2 glioblastoma. Toxicity (WHO grading) was mainly hematological: leukopenia (16.2% grade 3-4), neutropenia (29.7% grade 3-4), thrombopenia (27% grade 3-4). No other toxicity greater than grade 2 was observed. In conclusion, cystemustine at 60 mg/m2 has moderate clinical activity in relapsing glioma. Our results warrant further investigation of this agent with an increased dose or modified scheme. PMID- 11206010 TI - Surgery, tamoxifen, carboplatin, and radiotherapy in the treatment of newly diagnosed glioblastoma patients. AB - A historically controlled phase II study was undertaken to investigate the efficacy and toxicity of a postoperative treatment consisting of high-dose continuous tamoxifen, carboplatin and radiotherapy in patients with newly diagnosed glioblastoma. Between 1995 and 1998, 50 patients with newly diagnosed glioblastomas underwent surgery and were subsequently treated with 200 mg day(-1) tamoxifen continuously, 3 cycles of carboplatin (300 mg m(-2)), and radiotherapy. Survival data for a historical control group were calculated from respective prognostic indices and were obtained from studies with comparable patient populations treated with operation and radiotherapy only. In our study, the median time to tumor progression was 30 weeks and the median survival time (MST) 55 weeks (95% confidence interval: 46-63 weeks). The MST of the control group (48 weeks) showed to be within this interval. In addition to already known prognostic factors in malignant gliomas (age, Karnofsky performance score, extent of tumor resection), the gender (females lived longer than males, p = 0.0025) showed to influence survival. Serious side effects (thrombosis, pulmonary embolism) occurred in 6 patients. A high incidence of multifocal tumor recurrences (33%), which might be related to study-treatment, was observed. In conclusion, the combined therapy failed to demonstrate a higher efficacy than standard treatment for glioblastoma patients. PMID- 11206011 TI - FDG-PET as a prognostic factor in high-grade astrocytoma. AB - BACKGROUND: The prognostic value of the metabolic status of cerebral gliomas determined by positron emission tomography with [18F]-fluoro-deoxy-D-glucose (FDG PET) has been established in populations with a mixture of grades 2, 3 and 4 gliomas, but remains uncertain when only malignant gliomas are considered (grade 3 and 4). METHODS: FDG-PET performed in 30 patients with anaplastic astrocytoma (grade III) and 61 patients with glioblastoma (grade 4) were classified according to a metabolic grading. The uptake of FDG was lower in the tumor compared to white matter (WM) in grade 1 (4 glioblastoma, 4 anaplastic astrocytoma), it was intermediate between WM and cortex in grade 2 (20 glioblastoma, 22 anaplastic astrocytoma), and it was superior to cortex in grade 3 (38 glioblastoma, 4 anaplastic astrocytoma). RESULTS: Kaplan-Meier survival curves were similar in patient with grades 1 and 2, but were significantly worse (p = 0.007) in grade 3. In multivariate analysis considering age, pathological grade (anaplastic astrocytoma versus glioblastoma), and metabolic grades, the metabolic grade did not appear to be an independent prognostic factor. When anaplastic astrocytomas and glioblastomas were considered separately, metabolic grade is of predictive value only in the group of glioblastomas. CONCLUSION: In malignant gliomas, metabolic grading determined by FDG-PET was not superior to the pathological grading for survival prediction. Still, it remains of predictive value when applied to malignant gliomas histologically classified as glioblastoma. PMID- 11206012 TI - Hydroxyurea chemotherapy for unresectable or residual meningioma. AB - Meningiomas represent 18-20% of all intracranial tumors and have a 10-year recurrence rate of 20-50%, despite aggressive surgery and irradiation. In addition, many tumors are not amenable to surgery due to their deep location or proximity to delicate structures. Chemotherapy is being explored as another potential treatment option for unresectable or refractory meningiomas. Hydroxyurea is an agent that inhibits ribonucleotide reductase and can induce apoptosis in meningioma cell cultures and animal models. We have placed 17 patients with unresectable or residual meningioma on hydroxyurea chemotherapy (20 mg/kg/d orally). The mean age of our cohort was 57.2 years; 13 patients were female. Eleven patients had actively growing tumors or neurological progression at the onset of chemotherapy. Sixteen patients were evaluable for response. Fourteen of the 16 patients (88%) responded with stable disease ranging from 20 to 144+ weeks (median 80 weeks; 10 patients still accruing time). Three of the responders progressed after 20, 36, and 56 weeks, respectively. Two patients had progressive disease after 10 weeks. Toxicity was hematologic in most patients; leukopenia was most common. Nine patients (53%) required dosage reductions (250 500 mg/d) secondary to hematologic toxicity. Hydroxyurea appears to have modest activity against meningiomas and should be considered in patients with unresectable tumors or large residual tumors following surgical resection. PMID- 11206013 TI - Therapeutic adjuncts for immediate transfer to the catheterization laboratory in patients with acute coronary syndromes. AB - Early coronary intervention in patients with non-ST-segment elevation myocardial infarction (MI) and unstable angina may be made safer and more efficacious with concomitant therapies, including glycoprotein IIb/IIIa inhibitors and low molecular-weight heparins. Stent placement has been shown to improve procedural success and reduce major in-hospital complications when compared with balloon angioplasty alone in patients with unstable angina. However, unstable angina remains a major hazard for adverse coronary events in long-term follow-up after elective stent placement. The currently available glycoprotein IIb/IIIa inhibitors-eptifibatide, tirofiban, and abciximab--have each been shown to reduce ischemic events before percutaneous coronary intervention when administered to patients presenting with non-ST-segment elevation acute coronary syndromes in large clinical trials. The adjunctive role of low-molecular-weight heparins in this scenario has been largely unexplored. Enoxaparin, when given before angiography or percutaneous coronary intervention, has been shown to be superior to unfractionated heparin in preventing major coronary events. In this review, an algorithm for treatment of non-ST-segment elevation acute coronary syndromes is presented and the current role of these newer adjunctive pharmacotherapies is explored. In the future, combinations of these agents may prove to be most beneficial in patients undergoing early percutaneous coronary intervention. PMID- 11206015 TI - Introduction: evidence to practice in acute coronary syndromes. PMID- 11206014 TI - Calming the plaque to delay intervention for 24 hours in acute coronary syndromes. AB - One approach to management of patients with acute coronary syndromes involves use of pharmacologic therapy to passivate plaque for at least 24 hours before interventional procedures are undertaken. This approach is supported by the view that whatever subsequent treatment the patient receives will less likely be complicated. An important factor in revolutionizing treatment for acute coronary syndromes in recent years has been the introduction of potent new antithrombotic and antiplatelet pharmacologic therapies such as low-molecular-weight heparins and glycoprotein IIb/IIIa inhibitors. Incorporation of these newer agents into clinical practice, along with a better understanding of the pathophysiology underlying acute coronary syndromes, has contributed greatly to improved outcomes in these patients. Although the optimal methods for integrating the newer therapies remains to be determined, thus far, they have been shown to lower the risk of acute complications, as well as improve long-term results. PMID- 11206016 TI - An ischemia-guided approach for risk stratification in patients with acute coronary syndromes. AB - The optimal management approach for patients with non-ST-segment elevation acute coronary syndromes continues to be an issue of debate. An ischemia-guided strategy appears to be effective as an alternative to either a very conservative "wait-and-see" approach or a very aggressive routine revascularization approach. The need for another approach is supported by the lack of conclusive evidence based results favoring an early routine invasive treatment strategy. In the Thrombolysis in Myocardial Infarction (TIMI) IIIB trial, there were no differences in the incidence of death or myocardial infarction (MI) between patients treated with an early invasive approach and those treated with a conservative approach to treatment. Significantly worse outcomes were shown in patients assigned to an early invasive strategy in the Veterans Affairs Non-Q Wave Infarction Strategies in Hospital (VANQWISH) trial at 1-year follow-up (111 clinical events in the invasive group vs 85 in the conservative group; p = 0.05). Registry information, including that from the Organization to Assess Strategies for Ischemic Syndromes (OASIS), which included approximately 8,000 patients with unstable angina or suspected MI, has even suggested an excess hazard with a routine invasive approach. Patients with non-ST-segment elevation MI observed in the Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO)-IIB and Platelet IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trials also fared better with an ischemia-guided strategy. Even the recent FRagmin and Fast Revascularization during InStability in Coronary artery disease (FRISC II) trial investigators had to be very selective relative to eliminating high-risk patients in the first week and treating with intense anti-ischemic therapy and 5-7 days of low-molecular weight heparin therapy to show an advantage for assigned revascularization. A careful clinical evaluation with attention to early risk stratification is essential in the ischemia-guided approach. The Braunwald classification for unstable angina helps identify independent clinical predictors of a poor outcome; high risk is clearly associated with Braunwald class III and type C. Electrocardiographic and biochemical markers for myocardial necrosis (cardiac troponin T or I) are important tools for assessing the presence and degree of ischemia and associated risk for adverse outcome. Noninvasive evaluation of left ventricular ejection fraction is essential for identifying those at high risk due to impaired contractile function. When these conventional markers do not provide conclusive information, noninvasive stress testing is most helpful to further identify those at highest risk for revascularization. PMID- 11206017 TI - Acute coronary syndromes: extending medical intervention for five days before proceeding to revascularization. AB - Intensive medical therapy before percutaneous coronary intervention appears to improve results in patients with unstable angina and non-ST-segment elevation myocardial infarction (MI). In this review of treatment strategies for patients with acute coronary syndromes, an "aggressive conservative" approach based on that used in the FRagmin and Fast Revascularisation during InStability in Coronary artery disease (FRISC II) trial is recommended. In FRISC II, an early (but not emergent) invasive therapeutic procedure undertaken within 7 days of starting open-label dalteparin lowered the risk of death and MI in moderate- and high-risk patients and resulted in better and more rapid symptom relief and fewer hospital readmissions than the noninvasive approach. The early treatment period represents a critical juncture in the spectrum of care for patients with unstable angina and affords physicians the best opportunity to educate them about the importance of risk factor modification. Informed consent is also an important issue, particularly in the event of ad hoc coronary intervention. The optimal treatment plan must include considerations of length of hospitalization, medication requirements, and the potential for symptom recurrence or need for hospital readmission. Finally, tailoring therapy for individual patients and establishing appropriate timing of procedures will help ensure the best possible outcome. PMID- 11206018 TI - Avoidance of routine revascularization in the management of patients with non-ST segment elevation acute coronary syndromes. AB - A debate continues over whether a routine invasive or a conservative strategy is the best treatment approach for patients with non-ST-segment elevation acute coronary syndrome. The fundamental question underlying this debate is whether risk stratification should be an anatomy-driven or an ischemia-driven process. An early routine invasive or "drive-through" strategy, which consists of cardiac catheterization followed by percutaneous coronary intervention within 24 hours of the onset of angina, has not been shown to result in improved outcomes. In fact, investigators in the Veterans Affairs Non-Q-Wave Infarction Strategies in Hospital (VANQWISH) trial found that aggressively treated patients had significantly worse outcomes during the first year of follow-up than did those treated with a conservative strategy. In this overview, a conservative (ischemia guided) strategy with aggressive medical therapy is recommended for patients with non-ST-segment elevation acute coronary syndrome. This conservative treatment includes intensive antiplatelet, antithrombotic, and anti-ischemic therapy combined with careful clinical assessment and provocative testing. Patients undergo catheterization and revascularization only if spontaneous angina occurs or there is objective evidence of stress-induced myocardial ischemia. In the future, it may be revealed that only patients at high risk have real benefit from early aggressive therapy, but the same approach may result in harm to patients at low risk. Tailoring therapy to the level of risk is essential to optimizing efficacy and clinical outcomes. PMID- 11206019 TI - Thrombosis prophylaxis in the acutely ill medical patient: insights from the prophylaxis in MEDical patients with ENOXaparin (MEDENOX) trial. AB - The clinical benefit and cost-effectiveness of routine thromboprophylaxis in surgical patients has been well documented, but use of this approach in general medical patients remains controversial. Following is an overview of major insights from the prophylaxis in Medical patients with Enoxaparin (MEDENOX) trial, which was undertaken to evaluate the efficacy of 2 dosage regimens of the low-molecular-weight heparin enoxaparin for prevention of venous thromboembolism in acutely ill medical patients. MEDENOX was a prospective, double-blind, randomized, placebo-controlled trial, which enrolled 1,102 hospitalized patients from 68 centers in 9 countries. Patients were randomly assigned to receive 40 mg of enoxaparin, 20 mg of enoxaparin, or placebo, given subcutaneously once a day for 6-14 days. The primary outcome was venous thromboembolism (deep-vein thrombosis or pulmonary embolism) between days 1 and 14. At the 40-mg dose, the risk of venous thromboembolism was significantly reduced in patients with heart failure, as well as in patients with other medical illnesses, including respiratory failure, infectious disease, or rheumatic disorders. The incidence of venous thromboembolism was 5.5% in the group that received 40 mg of enoxaparin as compared with 14.9% in the group that received placebo (p <0.001), a benefit that was maintained at 3-month follow-up. There was no significant difference in the incidence of venous thromboembolism between the group that received 20 mg of enoxaparin (15%) and the placebo group. Adverse effects did not significantly differ between the placebo group and either enoxaparin group. This study clearly establishes an effective strategy for lowering the risk of venous thromboembolism in the acutely ill population and provides a framework for future trials in this area. PMID- 11206020 TI - Strategies of patient care in acute coronary syndromes: rationale for the Global Registry of Acute Coronary Events (GRACE) registry. AB - An abundance of evidence is available from large, randomized clinical trials supporting the efficacy of therapies for the management of patients with acute coronary syndromes. For ST-segment elevation myocardial infarction (MI), a variety of databases can be used to assess how these therapies, both pharmacologic and invasive, are being integrated into real practice. Little information is available, however, with regard to how newer treatments are actually being implemented for patients with unstable angina and non-ST-segment elevation MI. There are several important issues to consider in evaluating current treatment practices for acute coronary syndromes, including limitations of clinical trial databases, a trend toward progressive shortening of length of hospital stay, and variations in the availability of resources among treatment centers. In response to the need for a broader database that would address the global impact of clinical management practices in acute coronary syndromes, the Global Registry of Acute Coronary Events (GRACE) Registry has been established. The GRACE Registry will initially collect data on patient care from a variety of treatment centers in 14 countries, the plan being to eventually enroll 10,000 patients per year. This international observational database will obtain information on the complete spectrum of acute coronary syndromes, with the specific goals of describing diagnostic and treatment strategies, determining hospital outcomes, improving quality of care, and developing hypotheses for future clinical research. PMID- 11206021 TI - Health situation analysis in the Americas, 1999-2000. PMID- 11206023 TI - Outbreak of poliomyelitis in the Dominican Republic and Haiti. PMID- 11206024 TI - Case definitions. Syphilis. PMID- 11206022 TI - Interrupting measles transmission in the Americas. PMID- 11206025 TI - Dengue in Central America: the epidemics of 2000. PMID- 11206026 TI - West Nile virus in the Americas. PMID- 11206027 TI - European recommendations on surveillance of antituberculosis drug resistance. PMID- 11206028 TI - Malaria, Burundi. PMID- 11206030 TI - Social anxiety disorder: comorbidity and its implications. AB - Social anxiety disorder is an extremely common and potentially disabling psychiatric disorder. Generalized social anxiety disorder, a subtype of the disorder, is believed to be the most common and most severe form. It is also the form that is most often associated with other psychiatric disorders. Unless the clinician has a high index of suspicion, social anxiety disorder may remain undetected. The clinical and treatment implications of the most common psychiatric comorbidities associated with social anxiety disorder are discussed in this article, with a focus on major depression, panic disorder, posttraumatic stress disorder, and alcohol abuse/dependence. Other psychiatric disorders and some medical conditions commonly associated with social anxiety disorder are briefly mentioned. Finally, a differential diagnosis of social anxiety disorder is described. Individuals who present for treatment of other anxiety disorders, mood disorders, or alcohol/substance abuse disorders should be considered at risk for current but undetected social anxiety disorder. PMID- 11206029 TI - Social anxiety disorder: an unrecognized problem in primary care. AB - Social anxiety disorder, or social phobia, is one of the most common mental disorders, yet it remains underrecognized and undertreated. Individuals with social anxiety disorder frequently have psychiatric comorbidity, including mood, anxiety, and substance abuse disorders, that can further impair a person's ability to function. This article reviews the literature on social anxiety disorder and explores questions regarding its prevalence, rates of recognition and treatment, and natural history. The association between social anxiety disorder and psychiatric comorbidity and suicide is reviewed, as well as quality of-life issues, including the impact of social anxiety disorder on educational attainment, occupational functioning and financial dependency, marital status, and health care utilization. There is a need for further study and greater awareness among primary health care providers about the prevalence and treatment of social anxiety disorder. PMID- 11206031 TI - Social phobia: etiology, neurobiology, and treatment. AB - Social phobia is a common and often disabling condition, with an etiology that is not established. There is evidence at several levels for an interplay of biological and psychological processes in social phobia. Genetic studies show that both genetic and environmental factors are important, with evidence pointing to associations with 2 genetic conditions, autism and fragile X syndrome. Behavioral inhibition has emerged as an important precursor to social phobia and possibly to other anxiety disorders. Epidemiologic and clinical studies have suggested that factors within the family environment, such as overprotection, overcontrol, modeling of anxiety, criticism, and in some cases abuse, can play a role in the development of social phobia. During childhood, complex interactions between brain system disturbances that mediate responses to negative social cues and factors in the social setting may lead to the development of a distorted set of internal "blueprints" for social behavior. The impact of severe social anxiety on brain systems that mediate behavioral change may prevent patients from learning better "blueprints." These can be taught through cognitive-behavioral therapies. The effective control of social anxiety with medications enables patients to recover; whether recovery can last after discontinuation of medications may depend on whether a new "blueprint" has been developed and whether stable changes in affected brain systems have occurred. Neuroimaging techniques are at the early stage of identifying abnormalities at the neurotransmitter and systems levels. PMID- 11206032 TI - Current status of psychotherapeutic interventions for social phobia. AB - Psychotherapeutic interventions, especially the cognitive-behavioral psychotherapies, have been well studied as treatments for social phobia. The purposes of this article are to (1) enumerate and describe the varieties of cognitive-behavioral therapy (CBT) that have been applied to the treatment of social phobia, (2) provide a meta-analytic overview of the efficacy of these approaches, (3) examine the relative utility of CBT versus that of pharmacotherapy for social phobia, (4) examine the potential utility of multidisciplinary approaches to treatment, and (5) discuss possible future directions in the development of psychotherapeutic strategies for the treatment of social phobia, including the use of computers as adjunctive tools. PMID- 11206034 TI - Social phobia: prevalence and diagnostic threshold. AB - This article reviews the literature on the prevalence and demographic features of social phobia in both community and general medical settings. The age at onset of social phobia is examined, as are comorbid conditions. Important differences between social phobia as it appears in the community and in primary care settings are explored. We conclude that social phobia is common and associated with significant impairment in a number of life areas. We discuss the diagnostic threshold of social phobia and potential difficulties in differentiating this disorder from other mental disorders. PMID- 11206033 TI - Treatment of social phobia with antidepressants. AB - This article reviews evidence for the utility of antidepressant medications in the treatment of social phobia. Monoamine oxidase inhibitors (MAOIs) were the first antidepressants shown to be effective for social phobia, but dietary restrictions and a relatively high rate of adverse effects often relegate MAOIs to use after other treatments have been found ineffective. Reversible inhibitors of monoamine oxidase (RIMAs) hold promise as safer alternatives to MAOIs, but RIMAs may be less effective and are currently unavailable in the United States. Selective serotonin reuptake inhibitors (SSRIs), of which paroxetine has been the best studied in social phobia to date, have recently emerged as a first-line treatment for the generalized subtype of social phobia. The SSRIs are well tolerated and consistently have been shown to be efficacious in controlled trials. PMID- 11206035 TI - Benzodiazepines and anticonvulsants for social phobia (social anxiety disorder). AB - Both benzodiazepines and conventional anticonvulsants have been evaluated as treatments for social phobia (social anxiety disorder). Among the benzodiazepines, clonazepam is the best studied, although there is reason to expect that all benzodiazepine anxiolytics would be effective for this condition. Among the anticonvulsants, gabapentin and pregabalin, an analogue of gamma aminobutyric acid (GABA), have been shown to be more effective than placebo in double-blind studies. Other than a small negative open study of valproic acid for social phobia, there is a paucity of information on whether other anticonvulsants might be useful for this condition. PMID- 11206036 TI - Methadone maintenance treatment: is it possible to adapt the daily doses to the metabolic activity of the patient? AB - Controversy still exists concerning the proper daily dose of methadone to be used in opiate dependency treatment. Because it is admitted that serum methadone concentration may be significantly correlated with the amount of drug available at the receptor level, it could be interesting to predict the methadone daily doses necessary to reach such a serum concentration. The authors have attempted to correlate the serum methadone level with the daily intake, considering the metabolic activity of the patients. A poor correlation was found between methadone doses and methadone serum concentrations (r2 = 0.0409, p = 0.048). The test used to determine the metabolic activity of patients is the 6-OH cortisol/17 OH corticosteroids ratio in urine. This urinary 6-OH cortisol/17-OH corticosteroids ratio was tested because cortisol is metabolized through the same P450 cytochromes as methadone, namely cytochrome P450 3A4. This determination could be of interest because it could be tested before methadone administration to predict optimal doses. But when the authors tried to correlate the methadone serum concentration with the steroid ratio, they failed to find a significant correlation (r2 = 0.0046, N.S.), even when they took into account the daily doses (r2 = 0.0015, N.S.), most probably because of some limitations of the cortisol ratio. PMID- 11206037 TI - Relation between dosage of carbamazepine and concentration in hair and plasma samples from a compliant inpatient epileptic population. AB - Compliance is a problem in all areas of therapeutic medicine. Methods for its assessment are classified as either indirect or direct. Indirect assessment is based on criteria such as pill counts, questionnaires, and self-reporting; direct methods involve the analytic measurement of the drugs in biologic fluids such as plasma or urine. Drugs taken either therapeutically or recreationally become incorporated into hair. This prospective study investigated the relation between the daily intake of the antiepileptic drug carbamazepine and both its trough plasma and hair concentrations in a highly supervised inpatient population of patients with epilepsy during a period of 6 months. Results showed that although there was a significant variation between patients resulting from the substantial range in the daily intake of carbamazepine (800-2400 mg/day), the intrapatient variation in both trough plasma and hair concentrations during the 6-month period were not significantly different. The mean intrapatient percentage coefficient of variation in total plasma and hair concentrations of carbamazepine was 11.5 +/- 4.7 and 15.0 +/- 5.2, respectively, both of which were independent of the daily dosage. This relatively small intrapatient variation in hair concentration over time and its close relation to the plasma concentration suggests that hair analysis may be a complementary and useful technique in monitoring drug-taking behavior. PMID- 11206038 TI - Determination of sildenafil citrate in plasma by high-performance liquid chromatography and a case for the potential interaction of grapefruit juice with sildenafil citrate. AB - This study was designed to establish a simple and reliable assay method that could be routinely used in the clinical laboratory setting using liquid extraction and high-performance liquid chromatography (HPLC). In addition, a case of potential interaction of grapefruit juice with sildenafil citrate is presented. The peaks of sildenafil (measured as sildenafil salt) and internal standard were identified with an ultraviolet detector at 230 nm and detection limit at 10 ng/mL. In a single elderly male patient, grapefruit juice increased the Cmax of sildenafil by 42% (1067.7 ng/mL to 1517.0 ng/mL) although AUC was not significantly altered (4082.9 ng x h/mL to 4171.9 ng x h/mL) by grapefruit juice. Sildenafil could be determined in a simple and reliable method using HPLC with liquid extraction. This case indicated that grapefruit juice might increase the Cmax of sildenafil without significant change in AUC. A further study with an appropriate number of subjects is needed before determining the degree of interaction between grapefruit juice and sildenafil. PMID- 11206039 TI - Bioanalysis of racemic reboxetine and its desethylated metabolite in a therapeutic drug monitoring setting using solid phase extraction and HPLC. AB - Reboxetine is a new antidepressant drug acting as a potent and selective noradrenaline reuptake inhibitor on the noradrenergic neuronal system. Because of an expected interindividual variability in drug metabolism in the clinical practice the need for therapeutic drug monitoring routines in psychiatry is always a prominent feature. In this application, the preferred bioanalytic methodology was solid phase extraction combined with reversed-phase high performance liquid chromatography and ultraviolet detection at 210 nm. The technique proved reliable, with interday and intraday variation of less than 5% and a quantification limit for reboxetine and one of its main metabolites O desethylreboxetine (O-reboxetine) at 5 and 30 nmol/L, respectively. The method was applied on serum samples from 38 patients treated chronically with reboxetine. These samples were drawn as trough levels in steady state with a dosage range of 2-16 mg/day. They evidenced a mean reboxetine concentration that was fairly linear and dose proportional, although the variance in concentration was large between patients, even those taking the same dosage. O-reboxetine was detected in quantifiable amounts in only 1 of the 38 patients (<3%). In conclusion, these results suggest that a routine reboxetine therapeutic drug monitoring service that is robust enough to produce reliable and reproducible results may be introduced into everyday clinical practice. PMID- 11206040 TI - Mycophenolic acid plasma concentrations: influence of comedication. AB - Mycophenolate mofetil (MMF) in combination with cyclosporine (CsA) or Tacrolimus (TAC) has been show to be a potent immunosuppressive agent. The authors assessed the mycophenolic acid (MPA) plasma levels achieved in clinical practice and evaluated the effect of concomitant administration of CsA and TAC . One hundred forty transplant patients (kidney: 120 and lung: 20) received a triple immunosuppression regimen of CsA or TAC, prednisone and MMF. Twenty-two renal transplant patients received double therapy with MMF and prednisone. There was no correlation between MMF dose and MPA trough concentrations (r = -0.0657). The medians (range) of the MPA dose-to-concentration ratio (D/C) in the CsA and TAC groups were 0.90 (0.11-8.33) and 0.56 (0.11-14.3), respectively (p < 0.0001). According to the post transplant period (1-3, 4-6 and >6 months), D/C values were significantly lower in patients receiving MMF and TAC than those receiving MMF and CsA in all three periods. MPA levels in patients treated with MMF and CsA were significantly lower than those obtained in double therapy. The D/C ratio in CsA-treated patients, increased significantly (p = 0.0005) when CsA level increased. There was no relationship between D/C ratio and TAC blood concentrations. These results suggest that CsA exerts an influence on MPA trough levels, although further work is required to characterize the mechanism of interaction. PMID- 11206041 TI - Analytical validation for a series of marker compounds used to assess renal drug elimination processes. AB - Renal drug elimination is determined by glomerular filtration, tubular secretion, and tubular reabsorption. Changes in the integrity of these processes influence renal drug clearance, and these changes may not be detected by conventional measures of renal function such as creatinine clearance. The aim of the current study was to examine the analytic issues needed to develop a cocktail of marker drugs (fluconazole, rac-pindolol, para-aminohippuric acid, sinistrin) to measure simultaneously the mechanisms contributing to renal clearance. High-performance liquid chromatographic methods of analysis for fluconazole, pindolol, para aminohippuric acid, and creatinine and an enzymatic assay for sinistrin were developed or modified and then validated to allow determination of each of the compounds in both plasma and urine in the presence of all other marker drugs. A pilot clinical study in one volunteer was conducted to ensure that the assays were suitable for quantitating all the marker drugs to the sensitivity and specificity needed to allow accurate determination of individual renal clearances. The performance of all assays (plasma and urine) complied with published validation criteria. All standard curves displayed linearity over the concentration ranges required, with coefficients of correlation greater than 0.99. The precision of the interday and intraday variabilities of quality controls for each marker in plasma and urine were all less than 11.9% for each marker. Recoveries of markers (and internal standards) in plasma and urine were all at least 90%. All markers investigated were shown to be stable when plasma or urine was frozen and thawed. For all the assays developed, there were no interferences from other markers or endogenous substances. In a pilot clinical study, concentrations of all markers could be accurately and reproducibly determined for a sufficient duration of time after administration to calculate accurate renal clearance for each marker. This article presents details of the analytic techniques developed for measuring concentrations of marker drugs for different renal elimination processes administered as a single dose to define the processes contributing to renal drug elimination. PMID- 11206042 TI - Effective fluconazole therapy for liver transplant recipients during continuous hemodiafiltration. AB - Fungal infections are still one of the main causes of death and complications after solid organ and bone marrow transplants. The authors evaluated the effect of continuous hemodiafiltration (CHDF) on the pharmacokinetics of fluconazole in liver transplant recipients. Six liver transplant patients (primary biliary cirrhosis, n = 2; fulminant hepatitis, n = 2; viral hepatitis, n = 2) were enrolled in this study. In one patient not receiving CHDF, the fluconazole levels increased with increasing dosages. In contrast, in patients undergoing CHDF, the dosage of fluconazole was increased from 100 mg/d to 200 mg/d, but fluconazole did not reach the targeted levels. It appears that the targeted trough level cannot be achieved by administration of fluconazole at a dosage of 100 to 200 mg/d during CHDF. A higher dosage (600-1000 mg/d) of fluconazole may be required to achieve the therapeutic drug level in patients undergoing CHDF. In patients undergoing CHDF, fluconazole was given at a dosage of 800 mg/d and reached the targeted levels. In addition, after CHDF, the dosage of fluconazole was decreased to 100 mg/d, and fluconazole reached the near-targeted trough level. These results demonstrate that CHDF removes fluconazole from the blood at an efficiently high rate, resulting in its ineffective blood level. To guarantee safe and effective fluconazole therapy, the trough levels should be monitored routinely during CHDF. PMID- 11206043 TI - Urine drug screens in overdose patients do not contribute to immediate clinical management. AB - A prospective study assessed whether routine urine drug screens might alter the management of overdose patients. Urine was collected from 107 patients with a diagnosis of deliberate self-poisoning seen in the emergency department (ED) of a teaching hospital. The mean age of patients was 36 years (range 13-86 years) and 64% were female. All patients recovered after standard investigations and management, which did not include knowledge of urinary drug screen results. Two hundred ninety-seven compounds were detected in the 107 urine samples. Twenty percent were drugs administered in the ED. Sixty-five percent of patients were found to have taken more than one drug. Benzodiazepines were detected in 18% of samples, paracetamol in 10%, and alcohol in 8%. Sixty-one drugs, in 35 people, were identified that the patients did not report taking. Of these, paracetamol (10), benzodiazepines (9), and tetrahydrocannabinol (8) were the most common. All patients in whom paracetamol was found had already had paracetamol detected in blood and appropriate management instituted. If the results of urine screening had been immediately available this would not have affected the management or outcome of any patient. PMID- 11206044 TI - Fully automated on-line determination of olanzapine in serum for routine therapeutic drug monitoring. AB - A method is presented for unattended fully automated extraction and on-line determination of the atypical antipsychotic drug olanzapine in serum. An ASPEC automatic sample-preparing apparatus with Isolute cyanopropyl-bonded silicagel cartridges was used for solid-phase extraction of the drugs from serum. The adsorbed drugs were eluted with methanol and an aliquot injected into a high performance liquid chromatograph (HPLC) apparatus. Trifluoperazine was used as internal standard, and the analytes were separated on an unmodified silicagel column using methanol-ammonium acetate buffer pH 9.9 (85:15) as mobile phase. Ultraviolet detection at 257 nm was used for quantitation. Within the therapeutic range for the serum concentration of olanzapine, the interday variations for the quantitative determinations were <8%. Comparisons between concentrations measured using liquid-liquid extraction and the present on-line extraction method showed good agreement. Other drugs often used in combination with olanzapine did not interfere with the quantitative determinations. The method has been in routine use for more than 1 year for therapeutic drug monitoring. PMID- 11206045 TI - Sensitive and rapid method for the simultaneous quantification of the HIV protease inhibitors indinavir, nelfinavir, ritonavir, and saquinavir in human plasma by reversed-phase liquid chromatography. AB - A rapid, sensitive, and specific liquid chromatography method for the simultaneous determination of four protease inhibitors (indinavir, nelfinavir, ritonavir, and saquinavir) in human plasma is described. After a liquid-liquid extraction with terbutyl methyl ether and a sequential washing of the reconstituted sample with hexane, protease inhibitors are separated on a phenyl column using a simple binary mobile phase of ammonium acetate buffer:acetonitrile (48:52) (pH = 7.5) with an ultraviolet detection at 260 nm. The standard curves are linear in the range 0.025-1 microg/mL for saquinavir, 0.1-4 microg/mL for indinavir and nelfinavir, and 0.25-10 microg/mL for ritonavir, with an average recovery ranging from 79% to 99%, and with both low interday and intraday coefficients of variation (<15%). This assay is simple, rapid (15-minute interval between runs) , and useful for therapeutic monitoring of the protease inhibitors on a routine basis. PMID- 11206046 TI - Screening for detection of new antidepressants, neuroleptics, hypnotics, and their metabolites in urine by GC-MS developed using rat liver microsomes. AB - A gas chromatography-mass spectrometry (GC-MS) procedure for the detection of new antidepressants, neuroleptics, hypnotics, and their metabolites in urine is presented. The metabolites were first identified in rat liver microsome preparations by GC-MS after isolation and derivatization. Using these GC-MS data, a GC-MS screening was developed for urine as part of the authors' modified systematic toxicologic analysis procedure. After acid hydrolysis of a 2.5-mL aliquot of urine, a further aliquot was added. The mixture was then liquid-liquid extracted at pH 8-9, acetylated, and GC separated. Using mass chromatography with the ions m/z 58, 100, 120, 182, 195, 235, 261, 276, 284. and 293, the presence of new antidepressants, neuroleptics, hypnotics, and their metabolites could be indicated. Positive peaks could be identified by library search using the reference mass spectra recorded during the microsome studies. The intake of therapeutic doses of the following drugs could be monitored in urine: dosulepin, mirtazapine, moclobemide, nefazodone, trazodone, venlafaxine, and zolpidem. Olanzapine and zotepine were detectable in human urine only under steady-state conditions, and low-dose zopiclone was detectable only in overdose. The detection limit was less than 100 ng/mL (signal-to-noise ratio = 3) for the parent drugs. PMID- 11206047 TI - Effect of coadministered drugs and ethanol on the binding of therapeutic drugs to human serum in vitro. AB - The effects of coadministered drugs and ethanol on the binding of therapeutic drugs to human serum in vitro was investigated. Acetaminophen, lidocaine, phenobarbital, quinidine, theophylline, and valproic acid were added to pooled human serum at therapeutic concentrations. To each preparation was added one additional drug at three concentrations ranging from therapeutic to toxic. The following eight target drug/added drug combinations were studied: acetaminophen/phenobarbital. acetaminophen/theophylline, lidocaine/quinidine, phenobarbital/acetaminophen, phenobarbital/valproic acid, quinidine/lidocaine, theophylline/acetaminophen, and valproic acid/phenobarbital. Each serum without the other added drug as well as the serum supplemented with the other drug at the three concentrations was dialyzed against phosphate buffer. Similarly dialyzed were phenobarbital, quinidine, and theophylline, both alone at therapeutic concentrations in serum and with ethanol at three different concentrations in serum. The percentage of drug binding in each preparation was calculated. Acetaminophen diminished the binding of theophylline to human serum by a net change of 5.7% (percentage increase in free drug fraction [FDF], 11.0%) at 662 micromol/L and by a net change of 7.1% (percentage increase in FDF, 13.7%) at 1324 micromol/L. Theophylline decreased the binding of acetaminophen by a net change of 6.8% (percentage increase in FDF, 8.8%) at 277.5 micromol/L; phenobarbital reduced it by a net change of 6.6% (percentage increase in FDF, 8.5%) at 431 micromol/L. Valproic acid diminished binding of phenobarbital by a net change of 9.9% (percentage increase in FDF, 21.2%) at 1732 micromol/L. No significant effects were noted with other drug combinations or with the addition of ethanol. Coingestion of acetaminophen with theophylline, phenobarbital with acetaminophen, and valproic acid with phenobarbital at high to toxic concentrations decreases the binding of the target drug. The resulting increase in free drug concentration may lead to enhanced drug effect in vivo. PMID- 11206048 TI - Phenytoin intoxication induced by fluvoxamine. AB - A patient had phenytoin intoxication after administration of fluvoxamine, a selective serotonin reuptake inhibitor. The serum concentration of phenytoin increased dramatically from 16.6 to 49.1 microg/mL when fluvoxamine was coadministered, although the daily dosage of phenytoin and other drugs had not changed. During phenytoin and fluvoxamine treatment, ataxia, a typical side effect of phenytoin, was observed. The genotypes of CYP2C9 and 2C19, the enzymes responsible for phenytoin metabolism, were homozygous for the wild-type alleles (CYP2C9*1/*1 and 2C19*1/ *1). The interaction may be a result of inhibition of both CYP2C9 and 2C19 by fluvoxamine. PMID- 11206049 TI - Prediction of metabolic activity from genotype: the gene-dose effect of N acetyltransferase. AB - Metabolic activity of the polymorphic N-acetyltransferase (NAT2) is determined by the mutation pattern of the NAT2 gene. This results in interindividual differences in the metabolic capacity (the phenotype), with continuous distribution of the activities rather than qualitative distinction between rapid and slow acetylators. To determine whether the phenotype might be predicted solely from the mutation pattern of NAT2, quantitative relationships were calculated between mutation patterns of the NAT2 gene and the phenotype of NAT2 assessed either in vitro or in vivo. Healthy volunteers were examined for the velocity at which they metabolized sulfamethazine, and human liver cytosols were measured for NAT2 enzymatic activity, obtaining in vivo and in vitro metabolic phenotype, respectively. Typing of the NAT2 gene was performed by polymerase chain reaction, restriction fragment length analysis, or allele-specific polymerase chain reaction. Multiple linear regression analysis provided quantitative relationships between allelic pattern and the NAT2 activities measured in vivo and in vitro. Estimates showed the influence of particular allelic configurations on enzyme activity in vitro and the extent of acetylation of the probe drug in vivo, resulting in a strict gene-dose effect. Comparison of in vitro results with in vivo phenotyping figures showed a high degree of correspondence, indicating that the one is the reflection of the other. PMID- 11206050 TI - Design of a minimal protein oligomerization domain by a structural approach. AB - Because of the simplicity and regularity of the alpha-helical coiled coil relative to other structural motifs, it can be conveniently used to clarify the molecular interactions responsible for protein folding and stability. Here we describe the de novo design and characterization of a two heptad-repeat peptide stabilized by a complex network of inter- and intrahelical salt bridges. Circular dichroism spectroscopy and analytical ultracentrifugation show that this peptide is highly alpha-helical and 100% dimeric tinder physiological buffer conditions. Interestingly, the peptide was shown to switch its oligomerization state from a dimer to a trimer upon increasing ionic strength. The correctness of the rational design principles used here is supported by details of the atomic structure of the peptide deduced from X-ray crystallography. The structure of the peptide shows that it is not a molten globule but assumes a unique, native-like conformation. This de novo peptide thus represents an attractive model system for the design of a molecular recognition system. PMID- 11206051 TI - Cysteine-independent polymerization of metallothioneins in solutions and in crystals. AB - Polymerization of metallothioneins is one of the usually encountered puzzles during the research process of metallothioneins' structure and function. Our work focuses on the cysteine independently occurred polymerization from metallothioneins monomers in different milieus, while it leaves out the aggregation caused by the oxidation of cysteine, because the latter circumstance is the result of purification lapsus. After the purification of metallothioneins monomers, a dynamic light-scattering technique is used to detect the polymerized states of rabbit liver metallothionein I and II in different buffers, which is the first systematical detection of polymerized states of metallothioneins in solutions. The effects of different compositions of each buffer are discussed in details. Steric complementarity, hydrophobic, and electrostatic interaction characteristics are studied, following the modeling of monomers and relevant polymers of rat metallothionein II, rabbit liver metallothionein I and II. These theoretical calculations are the first complete computer simulations on different factors affecting metallothioneins' polymerization. A molecular recognition mechanism of metallothioneins' polymerization in solutions is proposed on the bases of experimental results and theoretical calculations. Preliminary X-ray studies of two crystal forms of rabbit liver metallothionein II are compared with the crystal structure of rat metallothionein II, and the polymerized states in crystal packing are discussed with the knowledge of polymerization of metallothioneins in solutions. The hypothesis, which is consistent with theoretical calculations and experimental results, is expected to construct a connection between the biochemical characteristics and physiological functions of metallothioneins, and this research may give some enlightenment to the topics of protein polymerizations. PMID- 11206052 TI - Automated search of natively folded protein fragments for high-throughput structure determination in structural genomics. AB - Structural genomic projects envision almost routine protein structure determinations, which are currently imaginable only for small proteins with molecular weights below 25,000 Da. For larger proteins, structural insight can be obtained by breaking them into small segments of amino acid sequences that can fold into native structures, even when isolated from the rest of the protein. Such segments are autonomously folding units (AFU) and have sizes suitable for fast structural analyses. Here, we propose to expand an intuitive procedure often employed for identifying biologically important domains to an automatic method for detecting putative folded protein fragments. The procedure is based on the recognition that large proteins can be regarded as a combination of independent domains conserved among diverse organisms. We thus have developed a program that reorganizes the output of BLAST searches and detects regions with a large number of similar sequences. To automate the detection process, it is reduced to a simple geometrical problem of recognizing rectangular shaped elevations in a graph that plots the number of similar sequences at each residue of a query sequence. We used our program to quantitatively corroborate the premise that segments with conserved sequences correspond to domains that fold into native structures. We applied our program to a test data set composed of 99 amino acid sequences containing 150 segments with structures listed in the Protein Data Bank, and thus known to fold into native structures. Overall, the fragments identified by our program have an almost 50% probability of forming a native structure, and comparable results are observed with sequences containing domain linkers classified in SCOP. Furthermore, we verified that our program identifies AFU in libraries from various organisms, and we found a significant number of AFU candidates for structural analysis, covering an estimated 5 to 20% of the genomic databases. Altogether, these results argue that methods based on sequence similarity can be useful for dissecting large proteins into small autonomously folding domains, and such methods may provide an efficient support to structural genomics projects. PMID- 11206053 TI - Thermodynamic and structural characterization of Asn and Ala residues in the disallowed II' region of the Ramachandran plot. AB - Residue Asn47 at position L1 of a type II' beta-turn of the alpha-spectrin SH3 domain is located in a disallowed region of the Ramachandran plot (phi = 56 +/- 12, psi = -118 +/- 17). Therefore, it is expected that replacement of Asn47 by Gly should result in a considerable stabilization of the protein. Thermodynamic analysis of the N47G and N47A mutants shows that the change in free energy is small (approximately 0.7 kcal/mol; approximately 3 kJ/mol) and comparable to that found when mutating a Gly to Ala in a alpha-helix or beta-sheet. X-ray structural analysis of these mutants shows that the conformation of the beta-turn does not change upon mutation and, therefore, that there is no relaxation of the structure, nor is there any gain or loss of interactions that could explain the small energy change. Our results indicate that the energetic definition of II' region of the Ramachandran plot (phi = 60 +/- 30, psi = -115 +/- 15) should be revised for at least Ala and Asn in structure validation and protein design. PMID- 11206054 TI - Structural comparison of Ntn-hydrolases. AB - The Ntn-hydrolases (N-terminal nucleophile) are a superfamily of diverse enzymes that has recently been characterized. All of the proteins in this family are activated autocatalytically; they contain an N-terminally located catalytic nucleophile, and they cleave an amide bond. In the present study, the structures of four enzymes of this superfamily are compared in more detail. Although the amino acid sequence homology is almost completely absent, the enzymes share a similar alphabeta betaalpha-core structure. The central beta-sheets in the core were found to have different packing angles, ranging from 5 to 35 degrees. In the Ntn-hydrolases under study, eight totally conserved secondary structure units were found (region C). Five of them were observed to contain the greatest number of conserved and functionally important residues and are therefore crucial for the structure and function of Ntn-hydrolases. Two additional regions, consisting of secondary structure units (regions A and B), were found to be in structurally similar locations, but in different orders in the polypeptide chain. The catalytic machinery is located in the structures in a similar manner, and thus the catalytic mechanisms of all of the enzymes are probably similar. However, the substrate binding and the oxyanion hole differed partially. PMID- 11206055 TI - Beta-helix core packing within the triple-stranded oligomerization domain of the P22 tailspike. AB - A right-handed parallel beta-helix of 400 residues in 13 tightly packed coils is a major motif of the chains forming the trimeric P22 tailspike adhesin. The beta helix domains of three identical subunits are side-by-side in the trimer and make predominantly hydrophilic inter-subunit contacts (Steinbacher S et al., 1994, Science 265:383-386). After the 13th coil the three individual beta-helices terminate and the chains wrap around each other to form three interdigitated beta sheets organized into the walls of a triangular prism. The beta-strands then separate and form antiparallel beta-sheets, but still defining a triangular prism in which each side is a beta-sheet from a different subunit (Seckler R, 1998, J Struct Biol 122:216-222). The subunit interfaces are buried in the triangular core of the prism, which is densely packed with hydrophobic side chains from the three beta-sheets. Examination of this structure reveals that its packed core maintains the same pattern of interior packing found in the left-handed beta helix, a single-chain structure. This packing is maintained in both the interdigitated parallel region of the prism and the following antiparallel sheet section. This oligomerization motif for the tailspike beta-helices presumably contributes to the very high thermal and detergent stability that is a property of the native tailspike adhesin. PMID- 11206056 TI - Functional prediction: identification of protein orthologs and paralogs. AB - Orthologs typically retain the same function in the course of evolution. Using beta-decarboxylating dehydrogenase family as a model, we demonstrate that orthologs can be confidently identified. The strategy is based on our recent findings that substitutions of only a few amino acid residues in these enzymes are sufficient to exchange substrate and coenzyme specificities. Hence, the few major specificity determinants can serve as reliable markers for determining orthologous or paralogous relationships. The power of this approach has been demonstrated by correcting similarity-based functional misassignment and discovering new genes and related pathways, and should be broadly applicable to other enzyme families. PMID- 11206057 TI - Backbone dynamics of sequence specific recognition and binding by the yeast Pho4 bHLH domain probed by NMR. AB - Backbone dynamics of the basic/helix-loop-helix domain of Pho4 from Saccharomyces cerevisae have been probed by NMR techniques, in the absence of DNA, nonspecifically bound to DNA and bound to cognate DNA. Alpha proton chemical shift indices and nuclear Overhauser effect patterns were used to elucidate the secondary structure in these states. These secondary structures are compared to the co-crystal complex of Pho4 bound to a cognate DNA sequence (Shimizu T. Toumoto A, Ihara K, Shimizu M, Kyogou Y, Ogawa N, Oshima Y, Hakoshima T, 1997, EMBO J 15: 4689-4697). The dynamic information provides insight into the nature of this DNA binding domain as it progresses from free in solution to a specifically bound DNA complex. Relative to the unbound form, we show that formation of either the nonspecific and cognate DNA bound complexes involves a large change in conformation and backbone dynamics of the basic region. The nonspecific and cognate complexes, however, have nearly identical secondary structure and backbone dynamics. We also present evidence for conformational flexibility at a highly conserved glutamate basic region residue. These results are discussed in relation to the mechanism of sequence specific recognition and binding. PMID- 11206058 TI - Evolution of binding affinity in a WW domain probed by phage display. AB - The WW domain is an approximately 38 residue peptide-binding motif that binds a variety of sequences, including the consensus sequence xPPxY. We have displayed hYAP65 WW on the surface of M13 phage and randomized one-third of its three stranded antiparallel beta-sheet. Improved binding to the hydrophobic peptide, GTPPPPYTVG (WW1), was selected in the presence of three different concentrations of proteinase K to simultaneously drive selection for improved stability as well as high-affinity binding. While some of the selected binders show cooperative unfolding transitions, others show noncooperative thermal unfolding curves. Two novel WW consensus sequences have been identified, which bind to the xPPxY motif with higher affinity than the wild-type hYAP65 WW domain. These WW domain sequences are not precedented in any natural WW domain sequence. Thus, there appear to be a large number of motifs capable of recognizing the target peptide sequence, only a subset of which appear to be used in natural proteins. PMID- 11206059 TI - Stability and peptide binding specificity of Btk SH2 domain: molecular basis for X-linked agammaglobulinemia. AB - X-linked agammaglobulinemia (XLA) is caused by mutations in the Bruton's tyrosine kinase (Btk). The absence of functional Btk leads to failure of B-cell development that incapacitates antibody production in XLA patients leading to recurrent bacterial infections. Btk SH2 domain is essential for phospholipase C gamma phosphorylation, and mutations in this domain were shown to cause XLA. Recently, the B-cell linker protein (BLNK) was found to interact with the SH2 domain of Btk, and this association is required for the activation of phospholipase C-gamma. However, the molecular basis for the interaction between the Btk SH2 domain and BLNK and the cause of XLA remain unclear. To understand the role of Btk in B-cell development, we have determined the stability and peptide binding affinity of the Btk SH2 domain. Our results indicate that both the structure and stability of Btk SH2 domain closely resemble with other SH2 domains, and it binds with phosphopeptides in the order pYEEI > pYDEP > pYMEM > pYLDL > pYIIP. We expressed the R288Q, R288W, L295P, R307G, R307T, Y334S, Y361C, L369F, and 1370M mutants of the Btk SH2 domain identified from XLA patients and measured their binding affinity with the phosphopeptides. Our studies revealed that mutation of R288 and R307 located in the phosphotyrosine binding site resulted in a more than 200-fold decrease in the peptide binding compared to L295, Y334, Y361, L369, and 1370 mutations in the pY + 3 hydrophobic binding pocket (approximately 3- to 17-folds). Furthermore, mutation of the Tyr residue at the betaD5 position reverses the binding order of Btk SH2 domain to pYIIP > pYLDL > pYDEP > pYMEM > pYEEI. This altered binding behavior of mutant Btk SH2 domain likely leads to XLA. PMID- 11206060 TI - Delineation of the calcineurin-interacting region of cyclophilin B. AB - The immunosuppressant drug cyclosporin A (CsA) inhibits T-cell function by blocking the phosphatase activity of calcineurin. This effect is mediated by formation of a complex between the drug and cyclophilin (CyP), which creates a composite surface able to make high-affinity contacts with calcineurin. In vitro, the CyPB/CsA complex is more effective in inhibiting calcineurin than the CyPA/CsA and CyPC/CsA complexes, pointing to fine structural differences in the calcineurin-binding region. To delineate the calcineurin-binding region of CyPB, we mutated several amino acids, located in two loops corresponding to CyPA regions known to be involved, as follows: R76A, G77H, D155R, and D158R. Compared to wild-type CyPB, the G77H, D155R, and D158R mutants had intact isomerase and CsA-binding activities, indicating that no major conformational changes had taken place. When complexed to CsA, they all displayed only reduced affinity for calcineurin and much decreased inhibition of calcineurin phosphatase activity. These results strongly suggest that the three amino acids G77, D155, and D158 are directly involved in the interaction of CyPB/CsA with calcineurin, in agreement with their exposed position. The G77, D155, and D158 residues are not maintained in CyPA and might therefore account for the higher affinity of the CyPB/CsA complex for calcineurin. PMID- 11206061 TI - The effects of disulfide bonds on the denatured state of barnase. AB - The effects of engineered disulfide bonds on protein stability are poorly understood because they can influence the structure, dynamics, and energetics of both the native and denatured states. To explore the effects of two engineered disulfide bonds on the stability of barnase, we have conducted a combined molecular dynamics and NMR study of the denatured state of the two mutants. As expected, the disulfide bonds constrain the denatured state. However, specific extended beta-sheet structure can also be detected in one of the mutant proteins. This mutant is also more stable than would be predicted. Our study suggests a possible cause of the very high stability conferred by this disulfide bond: the wild-type denatured ensemble is stabilized by a nonnative hydrophobic cluster, which is constrained from occurring in the mutant due to the formation of secondary structure. PMID- 11206062 TI - Chaperonin-assisted folding of glutamine synthetase under nonpermissive conditions: off-pathway aggregation propensity does not determine the co chaperonin requirement. AB - One of the proposed roles of the GroEL-GroES cavity is to provide an "infinite dilution" folding chamber where protein substrate can fold avoiding deleterious off-pathway aggregation. Support for this hypothesis has been strengthened by a number of studies that demonstrated a mandatory GroES requirement under nonpermissive solution conditions, i.e., the conditions where proteins cannot spontaneously fold. We have found that the refolding of glutamine synthetase (GS) does not follow this pattern. In the presence of natural osmolytes trimethylamine N-oxide (TMAO) or potassium glutamate, refolding GS monomers readily aggregate into very large inactive complexes and fail to reactivate even at low protein concentration. Surprisingly, under these "nonpermissive" folding conditions, GS can reactivate with GroEL and ATP alone and does not require the encapsulation by GroES. In contrast, the chaperonin dependent reactivation of GS under another nonpermissive condition of low Mg2+ (<2 mM MgCl2) shows an absolute requirement of GroES. High-performance liquid chromatography gel filtration analysis and irreversible misfolding kinetics show that a major species of the GS folding intermediates, generated under these "low Mg2+" conditions exist as long-lived metastable monomers that can be reactivated after a significantly delayed addition of the GroEL. Our results indicate that the GroES requirement for refolding of GS is not simply dictated by the aggregation propensity of this protein substrate. Our data also suggest that the GroEL-GroES encapsulated environment is not required under all nonpermissive folding conditions. PMID- 11206063 TI - Thermal stability of Clostridium pasteurianum rubredoxin: deconvoluting the contributions of the metal site and the protein. AB - To provide a framework for understanding the hyperthermostability of some rubredoxins, a comprehensive analysis of the thermally induced denaturation of rubredoxin (Rd) from the mesophile, Clostridium pasteurianum was undertaken. Rds with three different metals in its M(SCys)4 site (M = Fe3+/2+, Zn2+, or Cd2+) were examined. Kinetics of metal ion release were monitored anaerobically at several fixed temperatures between 40 and 100 degrees C, and during progressive heating of the iron-containing protein. Both methods gave a thermal stability of metal binding in the order Fe2+ << Fe3+ < Zn2+ < Cd2+. The temperature at which half of the iron was released from the protein in temperature ramp experiments was 69 degrees C for Fe2+ Rd and 83 degrees C for Fe3+ Rd. Temperature-dependent changes in the protein structure were monitored by differential scanning calorimetry, tryptophan fluorescence, binding of a fluorescent hydrophobic probe, and 1H NMR. Major but reversible structural changes, consisting of swelling of the hydrophobic core and opening of a loop region, were found to occur at temperatures (50-70 degrees C) much lower than those required for loss of the metal ion. For the three divalent metal ions, the results suggest that the onset of the reversible, lower-temperature structural changes is dependent on the size of the MS4 site, whereas the final, irreversible loss of metal ion is dependent on the inherent M-SCys bond strength. In the case of Fe3+ Rd, stoichiometric Fe3+/cysteine-ligand redox chemistry also occurs during metal ion loss. The results indicate that thermally induced unfolding of the native Cp Rd must surmount a significant kinetic barrier caused by stabilizing interactions both within the protein and within the M(SCys)4 site. PMID- 11206065 TI - Presence of closely spaced protein thiols on the surface of mammalian cells. AB - It has been proposed that certain cell-surface proteins undergo redox reactions, that is, transfer of hydrogens and electrons between closely spaced cysteine thiols that can lead to reduction, formation, or interchange of disulfide bonds. This concept was tested using a membrane-impermeable trivalent arsenical to identify closely spaced thiols in cell-surface proteins. We attached the trivalent arsenical, phenylarsenoxide, to the thiol of reduced glutathione to produce 4-(N-(S-glutathionylacetyl)amino)phenylarsenoxide (GSAO). GSAO bound tightly to synthetic, peptide, and protein dithiols like thioredoxin, but not to monothiols. To identify cell-surface proteins that contain closely spaced thiols, we attached a biotin moiety through a spacer arm to the primary amino group of the gamma-glutamyl residue of GSAO (GSAO-B). Incorporation of GSAO-B into proteins was assessed by measuring the biotin using streptavidin-peroxidase. Up to 12 distinct proteins were labeled with GSAO-B on the surface of endothelial and fibrosarcoma cells. The pattern of labeled proteins differed between the different cell types. Protein disulfide isomerase was one of the proteins on the endothelial and fibrosarcoma cell surface that incorporated GSAO-B. These findings demonstrate that the cell-surface environment can support the existence of closely spaced protein thiols and suggest that at least some of these thiols are redox active. PMID- 11206064 TI - Fibers of tau fragments, but not full length tau, exhibit a cross beta-structure: implications for the formation of paired helical filaments. AB - We have used X-ray fiber diffraction to probe the structure of fibers of tau and tau fragments. Fibers of fragments from the microtubule binding domain had a cross beta-structure that closely resembles that reported both for neurofibrillary tangles found in Alzheimer's disease brain and for fibrous lesions from other protein folding diseases. In contrast, fibers of full-length tau had a different, more complex structure. Despite major differences at the molecular level, all fiber types exhibited very similar morphology by electron microscopy. These results have a number of implications for understanding the etiology of Alzheimer's and other tauopathic diseases. The morphology of the peptide fibers suggests that the region in tau corresponding to the peptides plays a critical role in the nucleation of fiber assembly. The dramatically different structure of the full length tau fibers suggests that some region in tau has enough inherent structure to interfere with the formation of cross beta fibers. Additionally, the similar appearance by electron microscopy of fibrils with varying molecular structure suggests that different molecular arrangements may exist in other samples of fibers formed from tau. PMID- 11206066 TI - Resonant mirror biosensor analysis of type Ialpha cAMP-dependent protein kinase B domain--cyclic nucleotide interactions. AB - A resonant mirror biosensor was used to study cyclic nucleotide-receptor interactions. In particular, a novel method was developed to determine inhibition constants (Ki) from initial rates of ligate association to immobilized ligand. This approach was applied to the comparison of cyclic nucleotide-binding properties of the wild-type isolated B domain of the cAMP-dependent protein kinase type Ialpha regulatory subunit and its Ala-334-Thr (A334T) variant that has altered cyclic nucleotide specificity. A cUMP-saturated form of the B domain was used for all measurements. Under the conditions used, cUMP did not affect the kinetics of B domain association to immobilized cAMP. Triton X-100 was required to stabilize the protein at nanomolar concentrations. The association and dissociation rate constants for wild-type and A334T B domains yielded equilibrium dissociation constants of 11 and 16 nM. Heterogeneity of ligate and immobilized ligand, mass transport effects, and other factors were evaluated for their influence on biosensor-determined kinetic constants. Biosensor-determined relative inhibition constants (Ki' = Ki(cAMP)/Ki(analog)) for 16 cyclic nucleotide analogs correlated well with those determined by a [3H]cAMP binding assay. Previously published Ki' values for the B domain in the intact regulatory subunit were similar to those of the isolated B domain. The Ki' values for the wild-type and A334T B domains were essentially unchanged except for dramatic enhancements in affinity of cGMP analogs for the A334T B domain. These observations validate the isolated B domain as a simple model system for studying cyclic nucleotide-receptor interactions. PMID- 11206068 TI - Thirty-plus functional families from a single motif. AB - It is now possible to identify over 30 functional subfamilies among the WD-repeat containing proteins found in the completed genomes. The majority of these subfamilies have at least one member for which experimental data allow assignment to a cellular pathway or process. Half of the 63 WD-repeat-containing proteins in Saccharomyces cerevisiae, half of the 70 in Caenorhabditis elegans, and a third of the 100 plus predicted in Drosophila can be assigned to 23 of these functional subfamilies. Perhaps indicative of the future, 33 WD-repeat-containing proteins from the partial genome of Arabidopsis thaliana can now be assigned to 18 of these subfamilies. These assignments have been made possible by combining traditional sequence similarity with an implied common beta propeller structural context to obtain measures of protein-protein surface similarity. The beta propeller structural context is represented in the form of a Hidden Markov Model. The procedure is completely automated. PMID- 11206067 TI - The design of a hyperstable mutant of the Abp1p SH3 domain by sequence alignment analysis. AB - We have characterized the thermodynamic stability of the SH3 domain from the Saccharomyces cerevisiae Abp1p protein and found it to be relatively low compared to most other SH3 domains, with a Tm of 60 degrees C and a deltaGu of 3.08 kcal/mol. Analysis of a large alignment of SH3 domains led to the identification of atypical residues at eight positions in the wild-type Abp1p SH3 domain sequence that were subsequently replaced by the residue seen most frequently at that position in the alignment. Three of the eight mutants constructed in this way displayed increases in Tm ranging from 8 to 15 degrees C with concomitant increases in deltaGu of up to 1.4 kcal/mol. The effects of these substitutions on folding thermodynamics and kinetics were entirely additive, and a mutant containing all three was dramatically stabilized with a Tm greater than 90 degrees C and a deltaGu more than double that of the wild-type domain. The folding rate of this hyperstable mutant was 10-fold faster than wild-type, while its unfolding rate was fivefold slower. All of the stabilized mutants were still able to bind a target peptide with wild-type affinity. We have analyzed the stabilizing amino acid substitutions isolated in this study and several other similar sequence alignment based studies. In approximately 25% of cases, increased stability can be explained by enhanced propensity of the substituted residue for the local backbone conformation at the mutagenized site. PMID- 11206069 TI - Enhancement by Mg2+ of domain specificity in Ca2+-dependent interactions of calmodulin with target sequences. AB - Mg2+ binds to calmodulin without inducing the changes in secondary structure that are characteristic of Ca2+ binding, or the exposure of hydrophobic surfaces that are involved in typical Ca2+-dependent target interactions. The binding of Mg2+ does, however, produce significant spectroscopic changes in residues located in the Ca2+-binding loops, and the Mg-calmodulin complex is significantly different from apo-calmodulin in loop conformation. Direct measurement of Mg2+ binding constants, and the effects of Mg2+ on Ca2+ binding to calmodulin, are consistent with specific binding of Mg2+, in competition with Ca2+. Mg2+ increases the thermodynamic stability of calmodulin, and we conclude that under resting, nonstimulated conditions, cellular Mg2+ has a direct role in conferring stability on both domains of apo-calmodulin. Apo-calmodulin binds typical target sequences from skeletal muscle myosin light chain kinase and neuromodulin with Kd approximately 70-90 nM (at low ionic strength). These affinities are virtually unchanged by 5 mM Mg2+, in marked contrast to the strong enhancement of peptide affinity induced by Ca2+. Under conditions of stimulation and increased [Ca2+], Mg2+ has a role in directing the mode of initial target binding preferentially to the C-domain of calmodulin, due to the opposite relative affinities for binding of Ca2+ and Mg2+ to the two domains. Mg2+ thus amplifies the intrinsic differences of the domains, in a target specific manner. It also contributes to setting the Ca2+ threshold for enzyme activation and increases the importance of a partially Ca2+-saturated calmodulin-target complex that can act as a regulatory kinetic and equilibrium intermediate in Ca2+-dependent target interactions. PMID- 11206071 TI - Characterization of the interface structure of enzyme-inhibitor complex by using hydrogen-deuterium exchange and electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. AB - We investigated the interaction between a thiol protease inhibitor, cystatin, and its target enzyme, papain, by hydrogen-deuterium (H/D) exchange in conjunction with successive analysis by collision-induced dissociation (CID) in an rf-only hexapole ion guide with electrospray ionization-Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR MS). The deuterium incorporation into backbone amide hydrogens of cystatin was analyzed at different time points in the presence or absence of papain, examining the mass of each fragment produced by hexapole-CID. In the absence of papain, amide hydrogens in short amino-terminal fragments, such as b10(2+) and b12(2+), were highly deuterated within 1 min. Although fewer fragments were observed for the cystatin-papain complex in the hexapole-CID spectra, significant reductions in initial deuterium content were recognized throughout the sequence of cystatin. This suggests that complex formation restricted the flexibility of the whole cystatin molecule. Detailed analyses revealed that a marked reduction in deuterium content in the region of residues 1-10 persisted for hours, suggesting that the flexible N-terminal region was tightly fixed in the binding pocket with hydrogen bonds. Our results are consistent with those of previous studies on the structure and inhibition mechanism of cystatin. We demonstrated here that enzyme-inhibitor interactions can be characterized by H/D exchange in combination with CID in a hexapole ion guide using ESI-FTICR MS rapidly and using only a small amount of sample. PMID- 11206070 TI - Structural changes in alpha-synuclein affect its chaperone-like activity in vitro. AB - Alpha-synuclein, a major constituent of Lewy bodies (LBs) in Parkinson's disease (PD), has been implicated to play a critical role in synaptic events, such as neuronal plasticity during development, learning, and degeneration under pathological conditions, although the physiological function of alpha-synuclein has not yet been established. We here present biochemical evidence that recombinant alpha-synuclein has a chaperone-like function against thermal and chemical stress in vitro. In our experiments, alpha-synuclein protected glutathione S-transferase (GST) and aldolase from heat-induced precipitation, and alpha-lactalbumin and bovine serum albumin from dithiothreitol (DTT)-induced precipitation like other molecular chaperones. Moreover, preheating of alpha synuclein, which is believed to reorganize the molecular surface of alpha synuclein, increased the chaperone-like activity. Interestingly, in organic solvents, which promotes the formation of secondary structure, alpha-synuclein aggregated more easily than in its native condition, which eventually might abrogate the chaperone-like function of the protein. In addition, alpha-synuclein was also rapidly and significantly precipitated by heat in the presence of Zn2+ in vitro, whereas it was not affected by the presence of Ca2+ or Mg2+. Circular dichroism spectra confirmed that alpha-synuclein underwent conformational change in the presence of Zn2+. Taken together, our data suggest that alpha-synuclein could act as a molecular chaperone, and that the conformational change of the alpha-synuclein could explain the aggregation kinetics of alpha-synuclein, which may be related to the abolishment of the chaperonic-like activity. PMID- 11206072 TI - Methylene as a possible universal footprinting reagent that will include hydrophobic surface areas: overview and feasibility: properties of diazirine as a precursor. AB - Methylene is one of, if not the, most reactive organic chemical known. It has a very low specificity, which makes it essentially useless for synthesis, but suggests a possible role in protein footprinting with special importance in labeling solvent accessible nonpolar areas, identifying ligand binding sites, and outlining interaction areas on protomers that form homo or hetero oligomers in cellular assemblies. The singlet species is easily and conveniently formed by photolysis of diazirine. The reactions of interest are insertion into C-H bonds and addition to multiple bonds, both forming strong covalent bonds and stable compounds. Reaction with proteins and peptides is reported even in aqueous solutions where the vast majority of the reagent is used up in forming methanol. Species containing up to 5 to 10 extra :CH2 groups are easily detected by electrospray mass spectroscopy. In a mixture of a 14 Kd protein and a noninteracting 1.7 Kd peptide, the distribution of mass peaks in the electrospray spectra was close to that expected from random modification of the estimated solvent accessible area for the two molecules. For analysis at the single residue level, quantitation at labeling levels of one 13CH2 group per 10 to 20 kDa of protein appears to be possible with isotope ratio mass spectroscopy. In the absence of reactive solvents, photolysis of diazirine produces oily polymeric species that contain one or two nitrogen atoms, but not more, and are water soluble. PMID- 11206073 TI - An improved tripod amphiphile for membrane protein solubilization. AB - Intrinsic membrane proteins represent a large fraction of the proteins produced by living organisms and perform many crucial functions. Structural and functional characterization of membrane proteins generally requires that they be extracted from the native lipid bilayer and solubilized with a small synthetic amphiphile, for example, a detergent. We describe the development of a small molecule with a distinctive amphiphilic architecture, a "tripod amphiphile," that solubilizes both bacteriorhodopsin (BR) and bovine rhodopsin (Rho). The polar portion of this amphiphile contains an amide and an amine-oxide; small variations in this polar segment are found to have profound effects on protein solubilization properties. The optimal tripod amphiphile extracts both BR and Rho from the native membrane environments and maintains each protein in a monomeric native-like form for several weeks after delipidation. Tripod amphiphiles are designed to display greater conformational rigidity than conventional detergents, with the long-range goal of promoting membrane protein crystallization. The results reported here represent an important step toward that ultimate goal. PMID- 11206074 TI - Rationale for Bcl-xL/Bad peptide complex formation from structure, mutagenesis, and biophysical studies. AB - The three-dimensional structure of the anti-apoptotic protein Bcl-xL complexed to a 25-residue peptide from the death promoting region of Bad was determined using NMR spectroscopy. Although the overall structure is similar to Bcl-xL bound to a 16-residue peptide from the Bak protein (Sattler et al., 1997), the Bad peptide forms additional interactions with Bcl-xL. However, based upon site-directed mutagenesis experiments, these additional contacts do not account for the increased affinity of the Bad 25-mer for Bcl-xL compared to the Bad 16-mer. Rather, the increased helix propensity of the Bad 25-mer is primarily responsible for its greater affinity for Bcl-xL. Based on this observation, a pair of 16 residue peptides were designed and synthesized that were predicted to have a high helix propensity while maintaining the interactions important for complexation with Bcl-xL. Both peptides showed an increase in helix propensity compared to the wild-type and exhibited an enhanced affinity for Bcl-xL. PMID- 11206076 TI - N-terminal mutations in the anti-estradiol Fab 57-2 modify its hapten binding properties. AB - Recombinant antibodies often contain N-terminal mutations arising from the use of degenerate cloning primer sets and/or the introduction of restriction sites in the framework 1 regions. We studied the effects of such mutations in a recombinant anti-estradiol Fab fragment derived from the hybridoma cell line 57 2. The 5' ends of the heavy and light chain genes were originally modified to introduce the restriction sites XhoI and SacI, respectively, for cloning purposes. However, the affinity and specificity of the recombinant Fab were lowered compared to the proteolytic Fab' fragment of the parental hybridoma IgG. Replacing the mutated sites with authentic amino acid coding sequences restored the binding properties as well as increased the bacterial production levels fivefold and 10-fold at 30 and 37 degrees C, respectively. Local changes in the antigen binding site were probed by determining the affinity constants (Kd) for estradiol and four related steroids. It was found that the mutated heavy chain amino terminus specifically increased the Kd for testosterone whereas the mutated light chain amino terminus decreased the Kd for all of the steroids to the same extent; the heavy and light chain effects were additive. Analysis of a newly determined crystal structure of the authentic Fab 57-2 in complex with estradiol suggests that mutations in the residue 2 in V(H), and 2 and 4 in the V(L) domain were those responsible for the observed effects. Their general roles as structure determining residues for the CDR3 loops imply that similar effects can occur with other recombinant antibodies as well. PMID- 11206075 TI - Ab initio molecular dynamics studies on HIV-1 reverse transcriptase triphosphate binding site: implications for nucleoside-analog drug resistance. AB - Quantum-chemical methods are used to shed light on the functional role of residues involved in the resistance of HIV-1 reverse transcriptase against nucleoside-analog drugs. Ab initio molecular dynamics simulations are carried out for models representing the adduct between the triphosphate substrate and the nucleoside binding site. The triphosphate is considered either deprotonated or protonated at the gamma-position. Although the protonated form already experiences large rearrangements in the ps time scale, the fully deprotonated state exhibits a previously unrecognized low-barrier hydrogen bond between Lys65 and gamma-phosphate. Absence of this interaction in Lys65-->Arg HIV-1 RT might play a prominent role in the resistance of this mutant for nucleoside analogs (Gu Z et al., 1994b, Antimicrob Agents Chemother 38:275-281; Zhang D et al., 1994, Antimicrob Agents Chemother 38:282-287). Water molecules present in the active site, not detected in the X-ray structure, form a complex H-bond network. Among these waters, one may be crucial for substrate recognition as it bridges Gln151 and Arg72 with the beta-phosphate. Absence of this stabilizing interaction in Gln151-->Met HIV-1 RT mutant may be a key factor for the known drug resistance of this mutant toward dideoxy-type drugs and AZT (Shirasaka T et al., 1995, Proc Natl Acad Sci USA 92:2398-2402: Iversen AK et al., 1996, J Virol 70:1086-1090). PMID- 11206077 TI - The structure of the yrdC gene product from Escherichia coli reveals a new fold and suggests a role in RNA binding. AB - The yrdC family of genes codes for proteins that occur both independently and as a domain in proteins that have been implicated in regulation. An example for the latter case is the sua5 gene from yeast. SuaS was identified as a suppressor of a translation initiation defect in cytochrome c and is required for normal growth in yeast (Na JG, Pinto I, Hampsey M, 1992, Genetics 11:791-801). However, the function of the Sua5 protein remains unknown; Sua5 could act either at the transcriptional or the posttranscriptional levels to compensate for an aberrant translation start codon in the cyc gene. To potentially learn more about the function of YrdC and proteins featuring this domain, the crystal structure of the YrdC protein from Escherichia coli was determined at a resolution of 2.0 A. YrdC adopts a new fold with no obvious similarity to those of other proteins with known three-dimensional (3D) structure. The protein features a large concave surface on one side that exhibits a positive electrostatic potential. The dimensions of this depression, its curvature, and the fact that conserved basic amino acids are located at its floor suggest that YrdC may be a nucleic acid binding protein. An investigation of YrdC's binding affinities for single- and double-stranded RNA and DNA fragments as well as tRNAs demonstrates that YrdC binds preferentially to double-stranded RNA. Our work provides evidence that 3D structures of functionally uncharacterized gene products with unique sequences can yield novel folds and functional insights. PMID- 11206078 TI - A single amino acid substitution affects substrate specificity in cysteine proteinases from Fasciola hepatica. AB - The trematode Fasciola hepatica secretes a number of cathepsin L-like proteases that are proposed to be involved in feeding, migration, and immune evasion by the parasite. To date, six full cDNA sequences encoding cathepsin L preproproteins have been identified. Previous studies have demonstrated that one of these cathepsins (L2) is unusual in that it is able to cleave substrates with a proline in the P2 position, translating into an unusual ability (for a cysteine proteinase) to clot fibrinogen. In this study, we report the sequence of a novel cathepsin (L5) and compare the substrate specificity of a recombinant enzyme with that of recombinant cathepsin L2. Despite sharing 80% sequence identity with cathepsin L2, cathepsin L5 does not exhibit substantial catalytic activity against substrates containing proline in the P2 position. Molecular modeling studies suggested that a single amino acid change (L69Y) in the mature proteinases may account for the difference in specificity at the S2 subsite. Recombinant cathepsin L5/L69Y was expressed in yeast and a substantial increase in the ability of this variant to accommodate substrates with a proline residue in the P2 position was observed. Thus, we have identified a single amino acid substitution that can substantially influence the architecture of the S2 subsite of F. hepatica cathepsin L proteases. PMID- 11206079 TI - Fluorescence and 19F NMR evidence that phenylalanine, 3-L-fluorophenylalanine and 4-L-fluorophenylalanine bind to the L-leucine specific receptor of Escherichia coli. AB - The binding capacity of the L-leucine receptor from Escherichia coli was measured with L-phenylalanine and 4-fluoro-L-phenylalanine as substrates by fluorescence. The apparent dissociation constants (KD) for L-leucine, L-phenylalanine, and 4 fluoro-L-phenylalanine are 0.40, 0.18, and 0.26 respectively. 19F NMR data show protein-induced shifts for the 4-fluoro-L-phenylalanine peak and 3-fluoro-L phenylalanine when receptor is present. Evidence points to the binding of only the L-isomers of these fluorine analogs. PMID- 11206080 TI - Effect of deamidation on folding of ribonuclease A. AB - The folding of ribonuclease A (RNase A) has been extensively studied by characterizing the disulfide containing intermediates using different experimental conditions and analytical techniques. So far, some aspects still remain unclear such as the role of the loop 65-72 in the folding pathway. We have studied the oxidative folding of a RNase A derivative containing at position 67 the substitution Asn --> isoAsp where the local structure of the loop 65-72 has been modified keeping intact the C65-C72 disulfide bond. By comparing the folding behavior of this mutant to that of the wild-type protein, we found that the deamidation significantly decreases the folding rate and alters the folding pathway of RNase A. Results presented here shed light on the role of the 65-72 region in the folding process of RNase A and also clarifies the effect of the deamidation on the folding/unfolding processes. On a more general ground, this study represents the first characterization of the intermediates produced along the folding of a deamidated protein. PMID- 11206081 TI - A newly uncovered phenotype associated with the fruitless gene of Drosophila melanogaster: aggression-like head interactions between mutant males. AB - Male sexual behavior is regulated by the sex-determination hierarchy (SDH) in Drosophila melanogaster. The fruitless (fru) gene, one of the regulatory factors functioning downstream of other SDH factors, plays a prominent role in male sexual behavior. Here we demonstrate that fru mutations cause a previously unappreciated behavioral anomaly: high levels of head-to-head interactions between mutant males. These apparent confrontations between males are exhibited by all of the homozygous-viable fru mutants (expressing the effects of a given allele, among the four tested). Mutant dissatisfaction (dsf) males also exhibit this behavior at higher-than-normal levels, but it was barely displayed by doublesex or intersex mutants. For fru, a social component is involved in the head-interaction phenotype, while increasing age is a modifying factor for the behavior of dsf males. We suggest that head-to-head interactions, especially those performed by fru males, are instances of putative aggression analogous to those exhibited by wild-type males and that head interactions are, to an extent, operationally separable from courtship behavior. PMID- 11206082 TI - Two mouse lines selected for differential sensitivities to beta-carboline-induced seizures are also differentially sensitive to various pharmacological effects of other GABA(A) receptor ligands. AB - Two mouse lines were selectively bred according to their sensitivity (BS line) or resistance (BR line) to seizures induced by a single i.p. injection of methyl beta-carboline-3-carboxylate (beta-CCM), an inverse agonist of the GABA(A) receptor benzodiazepine site. Our aim was to characterize both lines' sensitivities to various physiological effects of other ligands of the GABA(A) receptor. We measured diazepam-induced anxiolysis with the elevated plus-maze test, diazepam-induced sedation by recording the vigilance states, and picrotoxin and pentylenetetrazol-induced seizures after i.p. injections. Results presented here show that the differential sensitivities of BS and BR lines to beta-CCM can be extended to diazepam, picrotoxin, and pentylenetetrazol, suggesting a genetic selection of a general sensitivity and resistance to several ligands of the GABA(A) receptor. PMID- 11206083 TI - Habituation of activity in an open field: A survey of inbred strains and F1 hybrids. AB - To determine if there is genetic variability in habituation of activity in an open field, we examined a number of inbred strains and F1 hybrids. Using 5-min exposures to a dark open field, we measured changes in exploratory behavior over 3 consecutive days in 129S3/SvImJ, A/J, BALB/ cByJ, C3H/HeJ, C57BL/6J, CBA/J, DBA/2J, FVB/NJ, (B6 x 129)F1/J, and (B6 x C3H) F1/J male and female mice. Strain differences in open-field activity and in habituation were evident. Some of the strain differences were further modified by sex. The strains and F1's could be separated into groups that increased, decreased, or did not modify their activities across testing sessions. In a second study, the effects of altering the floor surface on habituation were examined in male 129S3/SvImJ, C57BL/6J, DBA/2J, and (B6 x 129)F1/J mice. When the floor was altered after 3 consecutive days of habituation, increased activity levels were evident. There were strain differences in the responsiveness to the changes in the floor. These results confirm a genetic role in intersession habituation to an open field. PMID- 11206084 TI - Natal dispersal in rhesus macaques is related to serotonin transporter gene promoter variation. AB - A VNTR polymorphism previously characterized in the promoter region of the human serotonin transporter (SLC6A4) gene was also found to segregate two major alleles (l and s) among the free-ranging rhesus macaques of Cayo Santiago, Puerto Rico. When VNTR genotypes were related to age at male natal dispersal on Cayo Santiago, ss homozygotes (43 of 532 males tested) were found to have left their natal groups significantly earlier (age 57.1 +/- 2.6 months) than carriers of the l allele (ll age, 71.5 +/- 2.1 months; ls age, 63.5 +/- 1.5 months; P = 0.0001). Since migration implies reproductive costs and benefits that change with age at dispersal, migration at an intermediate age might have conferred a heterozygote advantage serving to maintain the VNTR polymorphism via overdominant selection. PMID- 11206085 TI - Self-Reported zygosity and the equal-environments assumption for psychiatric disorders in the Vietnam Era Twin Registry. AB - The equal-environments assumption (EEA) in twin studies of psychiatric disorders assumes that the family environment which contributes to risk for a disorder is equally correlated between monozygotic (MZ) and dizygotic (DZ) twin pairs. In a study of psychiatric disorders in female twins, Kendler and colleagues (1993) have demonstrated the utility of a test of the EEA which includes a specified family environmental factor defined by using measures of perceived zygosity. We tested the EEA assumption among 3155 male-male twin pair members of the Vietnam Era Twin Registry for the following DSM-III-R lifetime disorders: alcohol dependence, marijuana dependence, any illicit drug dependence, nicotine dependence, major depression, and posttraumatic stress disorder. The majority of MZ (81.6%; n = 1593) and DZ (90.2%; n = 1086) twin pairs agreed with the investigator's assigned zygosity. The best-fitting model for each of these disorders did not allow for a specified family environmental influence. These results support the usefulness of perceived zygosity in tests of the EEA. In male twin pairs, perceived zygosity has little impact on twin similarity for common psychiatric disorders. PMID- 11206086 TI - Multivariate genetic analysis of brain structure in an extended twin design. AB - The hunt for genes influencing behavior may be aided by the study of intermediate phenotypes for several reasons. First, intermediate phenotypes may be influenced by only a few genes, which facilitates their detection. Second, many intermediate phenotypes can be measured on a continuous quantitative scale and thus can be assessed in affected and unaffected individuals. Continuous measures increase the statistical power to detect genetic effects (Neale et al., 1994), and allow studies to be designed to collect data from informative subjects such as extreme concordant or discordant pairs. Intermediate phenotypes for discrete traits, such as psychiatric disorders, can be neurotransmitter levels, brain function, or structure. In this paper we conduct a multivariate analysis of data from 111 twin pairs and 34 additional siblings on cerebellar volume, intracranial space, and body height. The analysis is carried out on the raw data and specifies a model for the mean and the covariance structure. Results suggest that cerebellar volume and intracranial space vary with age and sex. Brain volumes tend to decrease slightly with age, and males generally have a larger brain volume than females. The remaining phenotypic variance of cerebellar volume is largely genetic (88%). These genetic factors partly overlap with the genetic factors that explain variance in intracranial space and body height. The applied method is presented as a general approach for the analysis of intermediate phenotypes in which the effects of correlated variables on the observed scores are modeled through multivariate analysis. PMID- 11206087 TI - Genetic and environmental causes of covariation in interview assessments of disruptive behavior in child and adolescent twins. AB - Multirater, face-to-face, interview data relating to conduct disorder (CD), oppositional-defiant disorder (ODD), and inattentive, impulsive, and hyperactive components of attention-deficit hyperactivity disorder (ADHD) in a population based sample of 1376 pairs of 8- to 16-year-old MZ and DZ twins are analyzed to examine (1) the genetic and environmental causes of correlation among ratings of ODD and CD symptoms and (2) the pattern of genetic and environmental correlation among the three components of ADHD. Parental ratings of ADHD showed marked sibling contrast effects, specific within raters but partly common across components. After these effects were removed, there was a modest genetic correlation between maternal and paternal ratings, but genetic effects were virtually uncorrelated across boys and girls. Genetic correlations among inattention, impulsivity, and hyperactivity were all large but fell well short of unity. There was little evidence that counts of symptoms of CD and ODD were genetically independent but the genetic correlations among ratings of twins, mothers, and fathers were all relatively modest. ODD and CD showed much higher genetic correlations across sexes than did the measures of ADHD. There was no evidence of rater contrast effects or of shared family environment influences in the twin resemblance for ODD and CD. PMID- 11206088 TI - The use of mixture models to perform quantitative tests for linkage disequilibrium, maternal effects, and parent-of-origin effects with incomplete subject-parent triads. AB - The transmission disequilibrium test and related methods require complete triads of genotyped cases plus both parents to test for linkage disequilibrium in the presence of population stratification. Based on the work of Weinberg (1999ab) and Schaid and Li (1997) with dichotomous outcomes, we discuss how additional tests for maternal or parent-of-origin effects can be performed and incomplete subject parent triads can be used in situations where the outcome is a quantitative variable. This is achieved using a finite mixture model where class membership is known for complete triads and unknown for incomplete triads. Simulations were performed assuming different genetic models and various amounts of missing parental genotypes. Results showed that the tests resulted in accurate Type I errors, recovered much of the loss in information caused by missing genotypes, and yielded unbiased parameter estimates. Extensions of the model to nuclear families, multiple loci, and multiple outcome variables are briefly discussed. PMID- 11206089 TI - Measurement models for sexual orientation in a community twin sample. AB - Multivariate structural equation modeling techniques have been applied to examine the causes of individual differences in responses to several items concerning sexual orientation. To minimize potential ascertainment and response biases, the study sample involved a large (N = 4901) community-based cohort of Australian twins aged 18-52 who answered an anonymous questionnaire on sexual behavior and attitudes. The statistical power of the analysis was increased by the availability of multiple measures of sexual orientation (behaviors, attitudes and feelings), providing stronger evidence for the existence of additive genetic influences on this phenotype than in a previous analysis (Bailey et al., 2000). Estimates of the heritability of homosexuality in this sample ranged between 50 and 60% in females but were significantly lower (heritability of approximately 30%) in males. PMID- 11206090 TI - Quality assurance, quality control and accreditation. PMID- 11206091 TI - [Contributions to animal husbandry in southern Germany and Austria in the late Middle Ages]. PMID- 11206092 TI - [Meat inspection in the second half of the 19th century, reflected in the progress of applied science]. PMID- 11206093 TI - [Collected sources for the biography of Swiss veterinarians in the 19th and 20th centuries (until 1985)]. PMID- 11206094 TI - [Veterinary occupations in the 16th through the 18th centuries]. PMID- 11206095 TI - [Nonsurgical therapy methods in hepatocellular carcinoma]. AB - The incidence of the hepatocellular carcinoma (HCC) is increasing in western countries mainly due to chronic hepatitis C. Therapy is dependent on the size and localization of the tumors as well as age and condition of the patient. If resection or transplantation are not possible, smaller tumors can be treated with local therapy either by percutaneous ethanol instillation, radiofrequency ablation or laser thermocoagulation. Larger tumors can be treated by transarterial chemoembolization which can also be combined with the methods named above. The results of systemic chemotherapy and medical treatment are disappointing. With early diagnosis and individualized therapeutic strategies prolongation of life or healing may be reached in many patients. PMID- 11206096 TI - [Clinical problem solving. Incidental finding during check-up examination for familial colorectal carcinoma susceptibility]. PMID- 11206097 TI - [Liver cell carcinoma--pathomorphology and differential diagnosis]. AB - Modern imaging techniques permit the detection of small and smaller nodular lesions of the liver. The classification and differential diagnosis of these lesions is still mainly based on pathomorphological analysis. With the exception of metastases from extra-hepatic malignant tumors, hepatocellular carcinoma is the most frequent malignant tumor of the liver. Whereas the classical variant of hepatocellular carcinoma preferentially arises in the cirrhotic liver, the fibrolamellar variant is found without association to cirrhosis and hepatitis B infection in the liver of young adults. Differential diagnosis of hepatocellular nodular lesions includes focal fatty change, focal nodular hyperplasia, liver cell adenoma, large regenerative nodules and dysplastic nodular lesions. PMID- 11206098 TI - [Liver resection and liver transplantation in liver cell adenoma, hepatocellular carcinoma and fibrolamellar liver carcinoma]. AB - Hepatocellular adenomas are rare benign conditions but represent an indication for resection due to their risk of rupture and malignant mutation. Surgical resection should include a safety margin according to oncologic principles. Surgical resection does represent the optimal treatment modality for hepatocellular carcinoma without accompanied cirrhosis of the liver. The rare fibrolamellar carcinoma has the best prognosis. Liver transplantation is usually not performed in HCC without cirrhosis. In case of HCC with cirrhosis in stage I and II the relapse free 5-year-survival rate is more than 50% after liver transplantation. In the UICC-stages III and IV the results of liver transplantation are worse, which points to the impact of exact preoperative staging. Liver resection in HCC and cirrhosis is indicated in stage I and II in case of good liver function. In case of liver resection the survival rates are worse with significantly higher relapses compared to liver transplantation. For small, functionally irresectable hepatocellular carcinoma in cirrhosis liver transplantation is the treatment of choice today. PMID- 11206099 TI - Left ventricular dysfunction and cytoprotection. AB - With the projections of increasing aging of the population, heart failure is expected to become a major health problem for most Western societies. Therefore, the study of the pathophysiological mechanisms involved in heart failure should be one of the main priorities of cardiovascular research. A substantial amount of knowledge has been gathered in the recent years on the mechanisms involved in the development of heart failure. One such mechanism is the development of myocyte's apoptosis. This apoptotic mechanism is responsible for a substantial decrease in the number of cardiac myocytes, and therefore for the worsening of heart failure. This apoptotic mechanism can be triggered by a number of mechanisms such as the adrenergic stimulation, the angiotensin II production, changes in calcium homeostasis, and changes in cellular metabolism. At least in theory, the development of therapies (such as beta blockers, ACE inhibitors, calcium channel blockers and trimetazidine) that can inhibit these mechanisms can have a cytoprotective role and therefore reduce the development of heart failure. Because of its main role in the production of energy for the cell, the mitochondrion is one of the mainframes of cell viability. If the mitochondrial function is decreased the myocyte will be in jeopardy. Therefore, drugs that can prevent mitochondrial dysfunction will obviously have a cytoprotective role in heart failure. PMID- 11206100 TI - Clinical benefits of a metabolic approach in the management of coronary patients. AB - Patients with Angina Pectoris benefit from therapy with nitrates, beta-blockers, and calcium channel antagonists. All these drugs, through different action mechanisms, tend to reduce cardiac work and restore the balance between myocardial metabolic demand and blood supply. Failure of this conventional haemodynamic treatment in controlling symptoms and preventing ischemia is however frequent, and many such patients are then referred for myocardial revascularization. This scenario has been innovated by Trimetazidine, an anti ischemic agent that exerts its beneficial effects by increasing cell tolerance to ischemia and improving functional recovery at the time of reperfusion. Compared with classic "hemodynamic" agents, Trimetazidine demonstrated similar efficacy in reducing frequency and severity of ischemic attacks and in increasing exercise tolerance, with a lower incidence of side effects. The adjunct of Trimetazidine to propranolol was found superior to nitrates in reducing ischemic episodes. In angina patients not controlled by CA-antagonists, Trimetazidine lowered the frequency of ischemic attacks and prolonged the time to ischemia during exercise. More recently, Trimetazidine has been shown to improve left ventricular dysfunction in patients with congestive heart failure, and in ischemic patients undergoing PTCA. In chronic coronary artery disease, Trimetazidine improved regional dysfunction at rest and during dobutamine stress echocardiography. Given the metabolic mechanism of action of Trimetazidine, focused on improving energy metabolism and restoring membrane homeostasis, it is expected to especially benefit patients in whom metabolic alteration contribute to the pathogenesis of ischemia, namely diabetic patients. Preliminary data from a multicenter study do support this hypothesis. In conclusion, available data indicate that the cardioprotective effect of Trimetazidine results in improvement of symptoms and preservation of left ventricular function in patients with acute and chronic ischemic syndromes. PMID- 11206101 TI - Trimetazidine as adjunctive therapy to primary PTCA for acute myocardial infarction. AB - Acute myocardial infarction remains a complex medical problem despite major advances in its management, especially early myocardial reperfusion by percutaneous transluminal coronary angioplasty (PTCA). Situations such as absence of TIMI 3 flow grade and/or persistence of ST segment elevation despite successful PTCA, no-reflow phenomenon and absence of improvement of myocardial regional contractility despite angiographic TIMI 3 flow, probably involve microvascular injury due to neutrophil and platelet activation, free radical generation and myocardial metabolic disorders. Trimetazidine is a well tolerated and efficient antianginal agent, that experimentally reduces ischemia-reperfusion injuries, neutrophil infiltration, platelet aggregation and has antioxidant effects. The Limitation of Infarct Size by trimetazidine Trial (LIST) randomized 94 patients with acute myocardial infarction undergoing primary PTCA into two groups: placebo versus trimetazidine i.v. infusion started before PTCA and continued for 48 hours. Continuous ST segment monitoring was performed during and after primary PTCA. The major results of the study were a significantly more important and faster reduction of ST segment elevation with a trend to less ST segment exacerbation, in the trimetazidine group after PTCA compared to the placebo group. These results suggest that trimetazidine may efficiently reduce ischemia-reperfusion lesions after primary PTCA for acute myocardial infarction. PMID- 11206102 TI - Trimetazidine and the contractile response of dysfunctional myocardium in ischaemic cardiomyopathy. AB - BACKGROUND: The therapeutic effect of anti-ischemic compounds is related to their ability to improve the oxygen supply-demand balance of the ischemic myocardium by increasing myocardial blood flow (calcium-antagonists), by reducing regional myocardial oxygen consumption (verapamil, betablockers) and increasing peripheral pooling of blood (nitrates, nifedipine). All these actions are also accompanied by hemodynamic changes, as evidenced by a lower double product, reduced wall stress, lower pulmonary wedge pressure, and lower systemic arterial pressure. In general, it was found that the combination of a betablocker with nifedipine improved the antianginal effect by further reducing the number and duration of ischemic events. The combination of a nitrate with a beta-blocker is particularly useful because it reduces the risk of heart failure by lowering left ventricular end-diastolic pressure and volume and by attenuating the negative inotropic effect of the betablocker. Although a combination therapy demonstrated benefits in comparison with drug treatment alone, it is associated with a higher incidence of untoward events. Trimetazidine (2, 3, 4 trimethoxybenzyl-piperazine dihydrochloride) is a novel anti-ischemic compound with a peculiar mechanism of action. Its anti-ischemic properties are unrelated to changes in myocardial oxygen supply-to-demand ratio, as shown by no significant effects on heart rate, blood pressure or rate-pressure product both at rest and during dynamic exercise. There are several possible mechanisms of action by which trimetazidine promotes preservation of membrane structures and cellular function: limitation of intracellular acidosis, correction of disturbances of transmembrane ion exchange leading to calcium overload, prevention of an excessive production of free radicals, inhibition of the inflammatory reaction and an antiplatelet effect. These documented actions cooperate to increase the rate of resynthesis of high energy phosphates within myocardial cells after episodes of ischemia. In several trials, trimetazidine has been tested as an antianginal agent, both as monotherapy and combined with "classical" anti-ischemic compounds. In comparison with nifedipine, trimetazidine had similar efficacy in reducing the number of weekly anginal attacks and in increasing the ischemic threshold in a group of 39 patients with stable angina. However, the incidence of side effects was significantly higher with nifedipine (5 vs 20), and affected 5 patients with trimetazidine and 13 patients with nifedipine (p = 0.03). In a relatively large European study involving 149 patients (Trimetazidine European Multicenter Study, TEMS), trimetazidine (20 mg t.i.d.) was compared with propranolol (40 mg t.i.d.) in patients with stable angina pectoris and documented significant coronary artery stenoses. The number of anginal attacks was reduced equally by both drugs and exercise duration was increased by both treatments. However, in contrast with propranolol trimetazidine did not alter the rate pressure product. In patients already treated with nifedipine or beta-blockers, the addition of trimetazidine (20 mg t.i.d.) was able to reduce the number and the duration of anginal attacks and improved also the exercise capacity. Trimetazidine is generally well tolerated and only minor side effects have been reported (drowsiness, sedation, diarrhea). The improvement in cardiac energy metabolism should theoretically translate into enhancement in mechanical efficiency. This hypothesis has been object of recent investigations in patients with ischemic heart disease with and without left ventricular dysfunction. Brottier, et al. demonstrated that patients with ischemic cardiomyopathy treated with trimetazidine had a higher ejection fraction (measured by radionuclide angiography) than control patients who received a placebo after 6 months of therapy (p < 0.018). The group of Chierchia demonstrated that trimetazidine improved ischemic regional myocardial dysfunction at rest and during stress-induced ischemia in 15 patients with chronic coronary artery disease without affecting the hemodynamic determinants of myocardial oxygen consumption. There is recent demonstration that trimetazidine improves the contractile response of left ventricular hibernating myocardium in patients with ischemic heart disease. Belardinelli et al. showed that trimetazidine improved the contractile response of dysfunctional myocardial to low-dose dobutamine in patients with ischemic heart disease and left ventricular function. Twenty-two patients with prior anterior myocardial infarction and injection fraction < 35% (33 +/- 7%) were randomized into 2 groups. A group (= 11) received trimetazidine (20 mg tid) for 2 months, while another group (= 11) received a placebo. The usual medications were not altered during the study. (ABSTRACT TRUNCATED) PMID- 11206103 TI - Ischaemic heart disease: clinical improvement with metabolic approach--final remarks. PMID- 11206104 TI - Ischaemic heart disease: clinical improvement with metabolic approach. AB - The term myocardial ischemia describes a condition which exists when fractional uptake of oxygen in the heart is not sufficient to maintain the rate of cellular oxidation. This leads to extremely complex situations which have extensively in recent years. A large amount of experimental research has been directed to establish the precise sequence of biochemical events leading to myocyte necrosis as such knowledge could lead to rational treatments designed to delay myocardial cell death. At the present time there is no simple answer to the question of what determines cell death and no recovery on reperfusion. Problems arise because: 1) ischemic-damage is not homogeneous and many factors may combine to cause cell death; 2) severity of biochemical changes and development of necrosis are usually associated (both the processes being dependent on the duration of ischemia) and it is impossible to establish a causal relationship; 3) the inevitability of necrosis can only be assessed by reperfusion of the ischaemic myocardium. Restoration of flow, however, might result in numerous further negative consequences, thus directly influencing the degree of recovery. From the clinical point of view, we have recently learnt that there are several potential manifestations and outcomes associated with myocardial ischaemia and reperfusion. Without doubt ventricular dysfunction (either systolic or diastolic) of the ischaemic zone is the most reliable clinical sign of ischemia, since ECG changes and symptoms are often absent. The ischaemia-induced ventricular dysfunction, at least initially, is reversible, as early reperfusion of the myocardium results in restoration of normal metabolism and contraction. In the ischaemic zone, recovery of contraction might occur instantaneously or, more frequently, with a considerable delay, thus yielding the condition recently recognised as the stunned myocardium. On the other hand, when ischemia is severe and prolonged, cell death might occur. Reperfusion at this stage is associated with the released of intracellular enzymes, disruption of cell membranes, influx of calcium, persistent reduction of contractility, and eventual necrosis of at least a portion of the tissue. This entity has been called reperfusion damage by those who believe that much of the injury is the consequence of events occurring at the moment of reperfusion rather than a result of changes occurring during the period of ischaemia. The existence of reperfusion damage, however, it has been questioned, and has been argued that, with the exception of induction of arrhythmias, it is difficult to be certain that reperfusion causes further injury. The existence of such an entity has clinical relevance, as it would imply the possibility of improving recovery with specific interventions applied at the time of reperfusion. In 1985 Rahimtoola described another possible out-come of myocardial ischemia. He demonstrated that late reperfusion (after months or even years) of an ischaemic area showing ventricular wall-motion abnormalities might restore normal metabolism and function. He was the first to introduce the term hibernating myocardium, referring to ischemic myocardium in which the myocytes remain viable but in which contraction is chronically depressed. Our data on metabolic changes occurring during ischemia followed by reperfusion which were obtained either in the isolated and perfused rabbit hearts or in CAD patient undergoing intracoronary thrombolysis or aortocoronary bypass grafting will be reviewed. PMID- 11206105 TI - Pharmacokinetics of netobimin and microsomal metabolism of albendazole in infected gerbils with Echinococcus granulosus. AB - A comparison of the pharmacokinetic profiles of netobimin (NTB), albendazole sulfoxide (ABZSO) and albendazole sulfone (ABZSO2) was performed in gerbils (Meriones unguiculatus) with intra-abdominal hydatidosis and in healthy gerbils. The infection was developed after peritoneal inoculation of protoscolices of Echinooccus granulosus from sheep. Plasma concentrations of NTB, ABZSO and ABZSO2 were measured by HPLC after oral administration of 50 mg NTB kg(-1). The results showed an incomplete biotransformation of NTB over the experimental time; and this increased in infected animals. ABZSO and ABZSO2 pharmacokinetic profiles were unaffected and were similar in both non-infected and infected animals. Both hepatic and intestinal microsomal sulfoxidase activities were measured. Since infected gerbils induced hepatic activity and decreased intestinal activity, the total activity was not different in infected and non-infected animals. In summary, intra-abdominal hydatid disease affected the pharmacokinetic profile of NTB, but ABZSO and ABZSO2 plasma concentrations were not different in infected and non-infected gerbils. PMID- 11206106 TI - Characterization of a proteasome alpha-chain from Giardia lamblia. AB - To begin to characterize the components of the 20S proteasome of Giardia lamblia, we have cloned a genomic sequence encoding an alpha-chain (type alpha3/C9, predicted size 244 amino acid residues). Southern analysis indicated that a single gene codes for this protein, and a Northern blot exhibited a single signal at 850 nt. An antiserum against a C-terminal fragment of the alpha-chain expressed in Escherichia coli reacted with a single protein band of Mr 27,000 that was present at constant levels in trophozoites and encysting cells. On a 2D blot of the purified 20S proteasome, we identified the cross-reacting component as a single protein of IEP 6.0, in agreement with the IEP predicted by the coding sequence. Our data confirm that the G. lamblia 20S proteasome is typically eukaryotic in containing a set of diverged alpha-subunits. PMID- 11206107 TI - A comparison of sporozoite transport after homologous and heterologous challenge in chickens immunized with the Guelph strain or the Florida strain of Eimeria maxima. AB - The two strains of Eimeria maxima, Guelph and Florida, used in this study were previously shown to only partially cross-protect immunologically with respect to lesion scores, weight gains and feed conversions after heterologous challenge. In this paper, we provide evidence that this partial lack of cross-protection is manifested at the level of sporozoite transport. In birds immunized and challenged with the homologous strain, sporozoites accumulated in the lamina propria and were blocked from further movement into the crypts by 72 h post challenge, unlike the situation observed in naive birds. Fewer than 5% of sporozoites were found in the crypts by 72 h post-challenge. In immunized birds challenged with the heterologous strain, fewer sporozoites reached the crypts than in naive birds but at least four times as many sporozoites successfully migrated to the crypts, when compared with birds challenged with the homologous strain. The degree of cross-protection afforded by the heterologous strain as measured by sporozoite transport success was not equally reciprocal. PMID- 11206108 TI - Novel small strongyle (Cyathostominae) beta-tubulin sequences. AB - Several coding sequences of the benzimidazole (BZ) target beta-tubulin have been described for different parasitic nematodes. However, until recently no tubulin sequences from Cyathostome species were available, despite the importance of BZ resistance in horses in the field. Here, we describe several full-length beta tubulin coding sequences of two major small strongyle species, namely Cylicocyclus nassatus and Cyathostomum coronatum. In the latter sequence, the putative BZ resistant mutation in codon 200 leading to a Phe to Tyr exchange is present. High nucleotide sequence similarities (>95%) were found among the tubulin sequences of the two different genera. This will be of advantage for the development of an allele-specific BZ resistance polymerase chain reaction (PCR) for multiple small strongyle species. PMID- 11206109 TI - Protection of hamsters from amebic liver abscess formation by immunization with the 150- and 170-kDa surface antigens of Entamoeba histolytica. AB - A monoclonal antibody, EH3015, prevents in vitro adherence of Entamoeba histolytica trophozoites to mammalian cells and inhibits amebic liver abscess formation in hamsters. By immunoaffinity chromatography with the monoclonal antibody, purified E. histolytica antigens with molecular masses of 150 and 170 kDa under non-reduced conditions were obtained. Hamsters were immunized with these antigens (group I) or with fractions further purified by polyacrylamide gel electrophoresis (group II). Pooled immune sera from the two groups inhibited in vitro amebic adherence to Chinese hamster ovary cells by 98% at 1:10 dilutions. The immunized hamsters were challenged by the intrahepatic injection of E. histolytica trophozoites. Complete protection from abscess formation was observed in 38% of hamsters in group I and 67% in group II, whereas all control hamsters inoculated only with adjuvant developed amebic liver abscesses. In the immunized hamsters, the abscesses in the two groups were significantly smaller than in the controls. These results demonstrate that the E. histolytica antigens are possible vaccine candidates for amebiasis. PMID- 11206110 TI - Parasite and vertebrate host genetic heterogeneity determine the outcome of infection by Schistosoma mansoni. AB - Intraspecific variation in Schistosoma mansoni infection and modulation of its expression by vertebrate host genetics was studied by evaluation of some biological parameters of the infection in BALB/c and C57BL/6 mice infected with one Brazilian (BH) and two Venezuelan (YT and SM) laboratory strains of the parasite. Mice infected with 60 cercariae of each parasite strain were euthanized at 5, 6, 8, and 12 weeks. Parameters recorded included the number of adult worms recovered by portal perfusion (infectivity); the number of eggs in the feces, the intestine, and the liver; and the ability of the eggs to cross the intestine, expressed as a quotient of the number of eggs in the intestine versus the feces. Results showed that the parasite appeared to determine the infectivity, the sex ratio, the onset and timing of oviposition, the number of eggs produced, initial egg laying toward the liver, and the ability to cross the intestinal wall. In this sense the BH strain appeared to be the most efficient and the SM strain, the most delayed; the YT strain was intermediate, although closer to the SM strain. On the other hand, the host appeared to influence the susceptibility to infection, the fecundity, and the percentage of eggs distributed in the liver and in the intestine during the chronic stage. In this sense, although they have been shown to be less susceptible to infection than BALB/c mice, C57BL/6 mice permit more eggs to be produced and exhibit similar numbers of eggs in the intestine and the liver at certain time points. It appears from these results that parasite genetics is essential for the outcome of infection with S. mansoni, but some characteristics may be quantitatively modulated by host genetics. PMID- 11206111 TI - Surface component characterization as taxonomic tools for Phytomonas spp identification. AB - The genus Phytomonas arbitrarily includes all protozoa of the family Trypanosomatidae isolated from plants, but its differentiation is a complex task. The phase separation technique using Triton X-114 was used to analyze hydrophobic and hydrophilic surface proteins in ten strains of Phytomonas isolated from various fruits. The iodination of surface proteins by the Iodo-Gen method was also used for Phytomonas isolates from tomatoes, corn and annatto, Herpetomonas samuelpessoai and Crithidia fasciculata. The distribution of protein-bound radioactivity in acrylamide gels was determined by autoradiograms and showed the presence of protein bands of 36-68 kDa in all strains of Phytomonas: there were two major bands at 88 kDa and 94 kDa, with minor bands at 36 kDa and 142 kDa in H. samuelpessoai; and there were three bands at 74, 86 and 94 kDa, with minor bands at 23 kDa and 105 kDa in C. fasciculata. The results demonstrated that samples of plant parasites can be clearly differentiated from H. samuelpessoai and C. fasciculata. These plant parasites were also submitted to polysaccharide analysis by gas-liquid chromatography of the corresponding alditol acetate. Arabinose, galactose, glucose and mannose, were the major monosaccharides found, while fucose, rhamnose and xylose were found in smaller amounts. The results of all these methods indicated that, after extension to a wider range of trypanosomatid strains, they may be useful in Phytomonas taxonomy. PMID- 11206112 TI - Assessment of Leishmania promastigote growth in vitro by means of nucleoside hydrolase activity determination. AB - Nucleoside hydrolases (NH) are involved in the purine salvage pathway of protozoan cells for the biosynthesis of nucleic acids. We developed a simple and reliable microassay based on N-ribohydrolase dosage using 4-nitrophenyl-beta-D ribofuranoside (NPR) substrate for the quantification of Leishmania infantum. The free promastigote stage of L. infantum contains high amounts of NH capable of cleaving NPR, but the parasitic amastigote does not. The method allows reliable quantification of viable parasites over a wide range of concentrations (5 x 10(4) 2 x 10(8) parasites ml(-1)) in a single assay. No difference in NH activity was observed between various strains at equivalent concentrations and growth curves determined with NH dosage were similar to optical counts. Samples can be stored at -20 degrees C for weeks before use in this unique assay without significant loss of NH activity. The method is particularly simple and versatile and proves well adapted for the determination of growth characteristics and drug screening studies of L. infantum promastigotes in vitro. PMID- 11206113 TI - The effect of interleukin-4 on the induction of intestinal mast cells and chronological cytokine profiles during intestinal nematode Strongyloides ratti infection. AB - The effect of interleukin-4 (IL-4) on the induction of intestinal mast cells and cytokine profiles during Strongyloides ratti infection was studied using IL-4 knockout (IL-4 KO) mice. The antigen-specific proliferative response of mesenteric lymph node cells was not impaired in IL-4 KO mice. The number of intestinal mast cells induced in IL-4 KO mice during S. ratti infection was 2- to 3-fold lower than that observed in WT mice. Intestinal mastocytosis had disappeared in IL-4 KO mice by day 21 postinfection, when significant mastocytosis continued to be observed in WT mice. In mesenteric lymphnode of IL-4 KO, IL-3 production decreased and mice IFN-gamma production significantly increased as compared with those of WT mice. The numbers of eggs excreted per gram of feces (EPG) by IL-4 KO mice were greater than those excreted by WT mice on day 6 postinfection, but no difference was observed in the subsequent period. In conclusion, intestinal mast cells are induced during S. ratti infection in the absence of IL-4, and IL-4 is not essential for protection against intestinal adult worms of S. ratti. PMID- 11206114 TI - The detection and occurrence of circulating antigens of Trichinella spiralis during worm development. AB - Four enzyme-based immunoassays were compared in detecting circulating antigens (CA) of Trichinella spiralis, i.e. microfluorescence, dissociated enhanced lanthanide fluoroimmunoassay (DELFIA), enhanced chemiluminescence and enzyme linked immunosorbent assay (ELISA). Parameters which could affect the sensitivity and specificity of the assays were evaluated. Different combinations of polyclonal antibody (PA) and five monoclonal antibodies (mAbs) against the excretory/secretory antigens of the nematode were tested to produce an optimal antigen-detecting system. DELFIA and a "sandwich" consisting of PA as capturing antibody and mAb 7C2C5 as detecting antibody, yielded the most stable and sensitive results; and 1 ng CA/ml could be detected. The assay did not cross react with heterologous antigens of Angiostrongylus cantonensis, Ascaris suum, Cysticercus cellulosae, Fasciolopsis buski, Gnathostoma hispidum and Trichuris suis. Fluctuating levels of CA were observed in the serum of experimentally infected mice at various periods post-infection. As early as days 4 and 6, a significant amount of CA was detected. The level reached a peak at day 10, then declined and another peak was observed at day 18. The monitoring of the corresponding antibody response by ELISA showed that IgM was first detected at day 10, reaching a peak at day 16. A marked increase in IgG1 was noted from day 16 and its level was significantly higher than that of IgG2. PMID- 11206116 TI - Prevalence of infection by the protozoan Hemolivia mariae in ticks. AB - This paper considers the prevalence of natural infections of the protozoan Hemolivia mariae, in its hosts the Australian sleepy lizard, Tiliqua rugosa, and the ixodid tick species, Amblyomma limbatum. We investigate whether the protozoan may be influencing the tick population in the field, by comparing the observed prevalence of infection in ticks with the prevalence expected from known transmission dynamics. The prevalence of infection in nymphs was similar to the expected prevalence, but the observed prevalence in adults was higher than expected. These results provide no evidence for infection-induced mortality in ticks. We also found that tick loads on infected and uninfected lizards were not significantly different and, overall, infected lizards were as likely to be tick infested as uninfected lizards. However, infected lizards were less likely to be found carrying female ticks. On balance, the evidence did not strongly support the hypothesis that ticks avoid feeding on infected lizards. We use known parameters of H. mariae transmission to estimate the rate of tick ingestion that may be required to sustain the observed prevalences in the field. PMID- 11206115 TI - Analysis for Giardia cysts and Cryptosporidium oocysts in water samples from small water systems in Taiwan. AB - Giardia and Cryptosporidium have emerged as waterborne pathogens of concern. Twenty-six water samples were collected from small water systems in Taiwan and checked for the occurrence of both parasites. Water quality parameters and characteristics of the sampling sites were also recorded. The frequencies of occurrence for Giardia and Cryptosporidium were 46.2% for each; and their mean concentrations were 79.5 cysts/100 l and 22.1 oocysts/100 l, respectively. The concentrations of oocysts and heterotrophic bacteria exhibited the highest correlation and followed the concentrations of the two protozoa. The water samples from sites with filtration devices had a lower oocyst concentration than those from sites without filtration devices, while no significant difference was found for cysts. The level of each parasite had no direct relationship with altitude. The cyst concentrations increased proportionally with the consumer population using the water systems. Risk assessment of the parasitic infections suggests that setting up disinfection devices in the small water systems would be needed. PMID- 11206117 TI - Megasome biogenesis in Leishmania amazonensis: a morphometric and cytochemical study. AB - Megasomes are large lysosomes found in the amastigote stage of Leishmania species belonging to the mexicana complex. The biogenesis of megasomes was investigated by transmission electron microscopy during the transformation of promastigotes into the amastigote form of L. amazonensis maintained in axenic cultures. Mainly small vacuoles with low electron density were found in the promastigote and early intermediate forms. Morphometrical analysis showed an increase in the volume density of these structures during the transformation process. Cysteine proteinase was localized in this structure by immunocytochemical assay. Membrane bounded structures filled with electron-dense material were also found in significant amounts from the 2nd day on. These structures were relatively abundant, both in axenic and lesion-derived amastigotes, but not in stable long term axenic amastigote culture. A three-dimensional reconstruction of lesion derived amastigotes and axenic amastigotes of L. amazonensis demonstrated that megasomes comprise almost 5% of the total cell volume. In addition, the development of other organelles was examined during the transformation process. PMID- 11206118 TI - Tissues and cells involved in the invasion of the rabbit intestinal tract by sporozoites of Eimeria coecicola. AB - This study was designed to identify an extra-intestinal route of migration of Eimeria coecicola sporozoites and the types of cell harbouring the parasite during the invasion of the intestine. The presence of E. coecicola in blood, spleen and mesenteric lymph nodes of infected donor rabbits was demonstrated by immunohistology on donor organs and measurement of oocyst excretion by coccidia free recipient rabbits injected with whole-cell suspensions prepared from donor tissues. Two types of donor lymphocyte, B (IgM+) and T (CD5+), were labelled using a two-colour immunofluorescence-labelling technique and separated with a cell-sorter (FACStar(Plus)). The presence of parasites in the sorted cells was assessed by direct examination and by using the same in vivo test after intravenous injection of IgM+ B or CD5+ T lymphocytes collected from donors at different times after inoculation. This test provided evidence that the parasites were alive and still infectious within the sorted lymphocytes. It was demonstrated that both B and T lymphocytes were infected. PMID- 11206119 TI - [Two children with extrapulmonary symptoms due to tuberculosis]. AB - Two patients came to their general practitioner for relatively minor problems: a 4-year-old boy came with a red eye and a 10-year-old girl with red foot soles. They came from Pakistan and Vietnam respectively. Their symptoms were due to tuberculosis, which diagnosis was established by Mantoux test and culture of a stomach aspirate. They were treated accordingly with isoniazid, rifampicin and pyrazinamide and with isoniazid, rifampicin and ethambutol respectively. These cases stress the importance of knowledge of the extrapulmonary manifestations of tuberculosis. As treatment exists and adequate treatment can diminish the reservoir of tuberculosis bacteria, early diagnosis can prevent the morbidity, spread and mortality of tuberculosis. PMID- 11206120 TI - [CBO guideline 'Breast cancer: screening and diagnosis']. AB - New developments in the diagnostic procedures for women with an increased risk for, or symptoms related to breast cancer led to development of new guidelines by a working group under the auspices of the Dutch Institute for Health Care Improvement, the Organisation of Comprehensive Cancer Centres and the National Breast Group of the Netherlands. Based on the best available evidence this working group formulated recommendations on the following topics: indications for screening within the population screening programme, screening outside the population screening programme, the diagnostic procedures of symptomatic and asymptomatic lesions in the breast and the organisation of the diagnostic work-up of patients with breast symptoms. The most important recommendations in the guidelines are: individual screening is recommended to certain groups of women who do not participate in the population screening programme, based on their risk profiles; available evidence does not support the extension of the population screening programme to women 40-49 years of age; diagnosis and treatment have to take place in a structured context, the so-called breast team; to guarantee optimal diagnostic procedures a multidisciplinary clinic is mandatory; the diagnostic work-up of breast abnormalities is based on the triple assessment: physical examination, imaging by mammography and/or ultrasound and needle biopsy. For quality-controlled implementation of this guideline, uniform prospective registration of patients, diagnosis and treatment related data is an important condition. PMID- 11206121 TI - [Screening for breast cancer on basis of individual risk assessment for women ineligible for the national population screening program]. AB - For healthy women, without malignancies in their personal histories, a positive family history for breast cancer is the single indication for individual breast surveillance outside the population screening. Management of women is based on individual risk assessment. A cumulative risk of 20% and more, as a result of a positive family history, will in practice be an indication for breast surveillance. This threshold is not evidence-based yet, nor are data available on the benefits of this surveillance efficacy. When a personal cumulative risk of more than 30% exists to develop breast cancer, a consultation with a clinical geneticist involved in a family cancer clinic should be offered. Surveillance of women with a high-risk cumulative risk should preferably be included in a prospective study design. Only in this way will data about compliance and the estimates of different ways of surveillance become available. There is no convincing evidence that population screening for women aged 40-49 years does lead to important mortality reduction in combination with a good balance between pros and cons for the women involved. Women in the age category 50-75 years, with breast cancer in their personal histories, who are not followed anymore, should be informed by their specialist about participating (again) in the population breast screening. There is no evidence of mortality reduction as a result of breast self-examination nor of palpation performed by a physician. However, awareness of the own body can be useful for early recognition of breast abnormalities; it may reduce the delay between the first recognizable symptom and the subsequently initiated therapy. PMID- 11206122 TI - [Quality control of DNA testing in hereditary diseases]. AB - The laboratories performing diagnostic studies regarding hereditary diseases and the specialists providing hereditary counselling are housed in clinical genetic centres. The laboratories are subject to the Special Medical Performances Act and have had licenses from the Ministry. The DNA diagnostic laboratories united in the National Committee on DNA Diagnostics, engaged among other things in quality control. The large number of tests requested and the dramatic consequences for the patient and his relatives necessitate high quality standards. The laboratories made a division of labour for analysis of most disorders, in order to acquire and maintain expertise in spite of rarity of most hereditary diseases. For adequate handling of requests for DNA diagnostic tests, it is important that the patient material be sent directly to the laboratory specialized in the disorders in question, for the request form to be filled out completely and for the patient data to be stated on the blood tube. A regularly updated review of the DNA diagnostics in the Netherlands can be found on the website: http://www.unimaas.nl/ approximately LOD/lod.htm. This list indications per centre and information such as required material and maximal results deadlines. PMID- 11206123 TI - [Diagnostic image (21). Small intestine necrosis due to mesenteric venous thrombosis]. AB - An 80-year-old woman was taken to the hospital because of acute abdominal pain. At laparotomy, necrosis of a segment of the small bowel was found, caused by mesenteric vein thrombosis. PMID- 11206124 TI - [High vaccination rates among children of Amsterdam]. AB - OBJECTIVE: To examine if in Amsterdam there are social or cultural groups of children with a relatively low vaccination coverage for diphtheria, pertussis, tetanus and poliomyelitis (DPTP) and mumps, measles and rubella (MMR). DESIGN: Descriptive cross-sectional study. METHOD: In the Department of Child Health Care of the Municipal Health Service of Amsterdam all 83,217 children aged 2-12 years living in Amsterdam on the 1st of January 2000 were analysed for vaccination and sociodemographic data collected routinely by the Department of Child Health Care. The sociodemographic data concerned sex, year of birth, country of birth of the mother and child, name of the school and postal code of the home address. Schools were grouped by (religious) affiliation on the basis of the Amsterdam school guide 1999/2000. Based on postal codes children were classified by the neighbourhoods in which they were living. Neighbourhoods were grouped by socio economic status based on data from the Central Bureau for Statistics. RESULTS: The overall vaccination rates of DPTP and MMR were 92.4% and 93.5% respectively. No important variation in vaccination coverage was identified between more and less affluent neighbourhoods. The uptake rate among foreign children was sometimes slightly higher and sometimes slightly lower compared with native children. Especially foreign children born abroad (Surinam, Antilles, Morocco, Turkey) were not fully vaccinated: 70.9% were fully immunized for DPTP, 79.5% for MMR. Children who visited anthroposophical schools were considerably less frequently fully immunized compared with children visiting other schools: for DPTP and MMR 81.0 and 59.9% respectively versus 94.4 en 95.3% for children attending general municipal schools. CONCLUSION: The vaccination coverage was high in children in Amsterdam. Further improvement of the vaccination uptake might be achieved by a more outreaching attitude to children born abroad, and by more intensely informing sceptical parents about the benefits and (supposed) dangers of vaccinations. PMID- 11206126 TI - [Fever and vesiculopapular exanthema due to infection with Rickettsia africae after a sojourn in South Africa]. AB - A 26-year-old woman, who had visited the Krugerpark in South Africa 5 days before, presented with fever, a skin lesion with a black crust (eschar), lymphadenopathy and a vesiculo papular rash. The clinical diagnosis 'Rickettsia africae infection' was confirmed by specific serological tests. A second patient aged 43 years, whose vesicular rash did not respond to flucloxacillin had been in the Krugerpark one week before and on examination was found with 2 eschars. Based on epidemiological and clinical grounds African tick fever can be distinguished from Mediterranean spotted fever (fievre boutonneuse). In the Netherlands specific diagnostic tests are not available. For treatment the distinction is not necessary; treatment is with tetracycline or doxycycline. Both patients recovered upon this treatment. PMID- 11206127 TI - [Definition of 'quack' in the public debate on alternative medicine]. AB - In May 1999 the Amsterdam Court of Justice decided that a retired internist and propagandist of his own alternative cancer therapy, could rightfully be called a quack by his critics. Recently this judgment was reversed on appeal. The first court used the medical definition of quackery: a treatment of which the supposed benefits are unsubstantiated. The court of appeal, however, took into consideration that to the general public calling someone a quack is an indication that this person is a swindler and practises medicine unlawfully. This definition is supported by the most authoritative Dutch dictionary. Apparently a different semantic interpretation of the term quack has led to these strongly diverging verdicts. The terms quack and quackery are indispensable in the public debate on alternative medicine. PMID- 11206128 TI - [Value of the 'non-diagnostic' lung scan--further classification of pulmonary embolism not reliable]. PMID- 11206129 TI - Identification and analysis of the myosin superfamily in Drosophila: a database approach. AB - The recent sequencing of the genome of Drosophila melanogaster has provided a valuable resource for mining the database for genes of interest. We took advantage of this opportunity in an attempt to identify novel myosins in Drosophila and confirm the presence of the previously identified myosins from classes I, II, III, V, VI, and VII. The Drosophila database annotators predicted the structure of three additional proteins which we identified as novel unconventional myosins, two of which fell into classes XV and XVIII, respectively. Our own efforts predicted the presence of four additional partial sequences that appear to be myosin proteins which did not fall into any specific class. In the future comparative genomics will hopefully lead to the placement of these myosins into new classes. PMID- 11206130 TI - Triad proteins and intracellular Ca2+ transients during development of human skeletal muscle cells in aneural and innervated cultures. AB - Dihydropyridine receptors (DHPRs), ryanodine receptors (RyRs), and triadin are major components of triads of mature skeletal muscle and play crucial roles in Ca2+ release in excitation-contraction (E-C) coupling. We investigated the expression and localization of these proteins as well as intracellular Ca2+ transients during development of human muscle cells cultured aneurally and innervated with rat spinal cord. mRNAs encoding skeletal muscle isoforms of the DHPR alpha1 subunit (alpha1S-DHPR), the RyR, and triadin were scarce in myoblasts and increased remarkably after myotube formation. Immunocytochemically, alpha1S DHPR was expressed after myoblast fusion and localized mainly within the cytoplasmic area of aneural myotubes whereas the cardiac isoform (alpha1C-DHPR) was abundant along the plasma membrane. RyRs and triadin were both detected after myotube formation and colocalized in the cytoplasm of aneural myotubes and innervated muscle fibers. Along the plasma membrane of aneural myotubes, colocalization of alpha1C-DHPR with the RyR was more frequently observed than that of alpha1S-DHPR. In innervated muscle fibers, alpha1S-DHPR and RyR were colocalized first along the plasma membrane and later in the cytoplasmic area and formed regular double rows of cross-striation. The alpha1C-DHPR diminished after innervation. In Ca2+ imaging, spontaneous irregular slow Ca2+ oscillations were observed in aneurally cultured myotubes whereas nerve-driven regular fast oscillations were observed in innervated muscle fibers. Both caffeine and depolarization induced Ca2+ transients in aneurally cultured myotubes and innervated muscle fibers. In aneurally cultured myotubes, depolarization-induced Ca2+ transients were highly dependent on extracellular Ca2+, suggesting immaturity of the Ca2+ release system. This dependence remarkably decreased after innervation. Our present results show that these proteins are expressed differently in aneurally cultured myotubes than in adult skeletal muscle, that Ca2+ release in aneurally cultured myotubes is different from in adult skeletal muscle, and that innervation induces formation of a mature skeletal muscle-like excitation-contraction coupling system in cultured human muscle cells. PMID- 11206131 TI - Slow troponin T mRNA in striated muscles is expressed in both cell type and developmental stage specific manner. AB - We have cloned cDNA sequences of both rat and mouse slow troponin T gene. These sequences share a high level of homology with each other and with the human slow troponin T gene although we were unable to detect an alternatively spliced exon present at 3' end of human slow troponin T cDNA in either mouse or rat cDNAs. Northern blot analysis detected a high level expression of slow troponin T in adult mouse Soleus with a lower level expression in mixed postnatal skeletal muscles. Unlike late fetal and postnatal skeletal muscles in which slow troponin T expression is restricted to slow muscle fibre rich regions only, in situ hybridisation analysis detected this isoform to be highly expressed in somitic myotome and all muscle masses at 10-14 days of gestation after which its expression was rapidly downregulated. The unexpected expression of slow troponin T mRNA in fetal heart was apparent by both northern blotting and in situ hybridisation analyses. Slow troponin T mRNA in fetal heart was first detected at 10 day in utero reaching maximum levels of expression at 12-15 days gestation. The slow troponin T in the heart was mainly expressed in the ventral ventricles until day 15 after which low level expression was also observed in both atria. Slow troponin T mRNA in both atrium and ventricle was mainly expressed in outer wall of the myocardium although it was also expressed in interventricular septum. This study therefore shows that in addition to being a cell type specific marker during later fetal and postnatal skeletal muscle development, slow troponin T represented one of the major developmental isoforms expressed in embryonic and fetal skeletal muscle as well as in the cardiac muscle. PMID- 11206132 TI - A novel Ca2+ binding protein associated with caldesmon in Ca2+-regulated smooth muscle thin filaments: evidence for a structurally altered form of calmodulin. AB - Smooth muscle thin filaments are made up of actin, tropomyosin, the inhibitory protein caldesmon and a Ca2+-binding protein. Thin filament activation of myosin MgATPase is Ca2+-regulated but thin filaments assembled from smooth muscle actin, tropomyosin and caldesmon plus brain or aorta calmodulin are not Ca2+-regulated at 25 degrees C/50 mM KCl. We isolated the Ca2+-binding protein (CaBP) from smooth muscle thin filaments by DEAE fast-flow chromatography in 6 M urea and phenyl sepharose chromatography using sheep aorta as our starting material. CaBP combines with smooth muscle actin, tropomyosin and caldesmon to reconstitute a normally regulated thin filament at 25 degrees C/50 mM KCl. It reverses caldesmon inhibition at pCa5 under conditions where CaM is largely inactive, it binds to caldesmon when complexed with actin and tropomyosin rather than displacing it and it binds to caldesmon independently of [Ca2+]. Amino acid sequencing, and electrospray mass spectrometry show the CaBP is identical to CaM. Structural probes indicate it is different: calmodulin increases caldesmon tryptophan fluorescence but CaBP does not. The distribution of charged species in electrospray mass spectrometry and nozzle skimmer fragmentation patterns are different indicating a less stable N-terminal lobe for CaBP. Brief heating abolishes these special properties of the CaBP. Mass spectrometry in aqueous buffer showed no evidence for the presence of any covalent or non-covalently bound adduct. The only remaining conclusion is that CaBP is calmodulin locked in a metastable altered state. PMID- 11206133 TI - Myostatin levels in regenerating rat muscles and in myogenic cell cultures. AB - Myostatin is a newly described member of the TGF-beta superfamily acting as a secreted negative regulator of skeletal muscle mass in several species, but whose mode of action remains largely unknown. In the present work, we followed the myostatin mRNA and protein levels in rat soleus and extensor digitorum longus (EDL) muscles regenerating in vivo from notexin-induced necrosis, and the myostatin transcript levels in two different in vitro myogenic differentiation models: i.e. in mouse BC3H1 and C2Cl2 cultured cells. The in vivo regenerating rat skeletal muscles showed a characteristic time-dependent expression of myostatin mRNA. After notexin injection, the transcript levels dropped below the detection limit on day 1 in soleus and close to the detection limit on day 3 in EDL, then increased to a maximum on day 7 in soleus and after 28 days finally reached the control values in both types of muscles. In contrast, the myostatin protein levels increased dramatically on the first days of regeneration in both muscles, i.e. at the time when its transcript level was low. Later on the myostatin protein level gradually declined to normal in soleus while in EDL it stayed high some days longer and decreased to normal on days 21-28. In vitro proliferating myoblasts produced low level of myostatin mRNA, which increased upon induction of differentiation suggesting that functional innervation is no prerequisite for myostatin expression. Myostatin production in vitro seems not to be dependent on myocyte fusion either, since it is observed in differentiated BC3H1 cells, which are defective in myofiber formation. PMID- 11206134 TI - Sarcomere length changes during end-held (isometric) contractions in intact mammalian (rat) fast and slow muscle fibres. AB - The sarcomere length change, within a 2 mm region, during end-held isometric contractions in intact rat fast and slow muscle fibre bundles was investigated at 20 degrees C and an initial sarcomere length of 2.68 microm using He-Ne laser diffraction. In some experiments, the fibre segment displacement was monitored with markers (pieces of human hair) placed at regular intervals on the surface of the muscle fibre bundles. The sarcomere length changes, monitored near the proximal end of the bundle (transducer end), during tetanic contractions were similar to those previously reported in frog muscle fibres. Thus, throughout the tension plateau, sarcomere length remained constant (and shortened) but showed evidence of non-uniform sarcomere behaviour (further shortening) during the rapid tension relaxation phase. Such non-uniform behaviour was not seen during twitch contractions. During a twitch contraction, sarcomeres at the proximal end shortened rapidly at first and continued to shorten--or remained shortened--until the tension had relaxed to between 20-23% of its peak value before lengthening back to the original length. The maximum twitch sarcomere shortening (mean +/- SEM) was 5.9 +/- 0.2% (n = 16) in fast and 5.4 +/- 0.3% (n = 14) in slow fibre bundles at 20 degrees C; sarcomere shortening near body temperature (approximately 35 degrees C) was greater, 8.8 +/- 0.2% (n = 7) in fast and 8.1 +/ 0.2% (n = 5) in slow fibre bundles. Increasing the initial sarcomere length of a preparation decreased the extent of sarcomere shortening and reducing the amount of sarcomere shortening, by sarcomere length clamping, markedly increased the peak twitch tension without significantly altering the twitch time course. When examined at different positions along muscle fibres, a sarcomere shortening was observed along much of the fibre length in most preparations. However, in about a third of the preparations some sarcomere lengthening was recorded in the distal end, but its amplitude was too small to accommodate the fibre shortening elsewhere. Complementary data were obtained using the surface marker technique. The displacement was largest and in opposite--but fibre shortening--direction in the markers placed approximately 0.5-1.0 mm away from the two tendon attachments; the markers placed at or near the centre of the fibre bundle showed the least amount of displacement. The findings suggest that the compliant region, where lengthening occurs, is at fibre ends, i.e. near myotendinous junction. PMID- 11206135 TI - p0071, a member of the armadillo multigene family, is a constituent of sarcomeric I-bands in human skeletal muscle. AB - p0071 is a member of the armadillo gene family that is expressed in a wide variety of mammalian tissues and cell types with a prominent cell-cell contact association in epithelial cells. Here, we report the expression and localization patterns of p0071 in differentiating human skeletal muscle cells and in normal and diseased human skeletal muscle tissues. Northern blots revealed expression of p0071 mRNA in adult skeletal muscle tissue. RT-PCR analysis and Western blotting experiments identified two differentially spliced isoforms of p0071. The balance between these isoforms shifted during in vitro differentiation of isolated muscle cells from predominant expression of the short variant to a preponderance of the larger variant from day 6 onwards. Immunolocalization studies in mature skeletal muscle tissue revealed that p0071 is a constituent of myofibrils with a distinct localization at the level of sarcomeric N2-lines. During myofibrillogenesis, p0071 was not detected in non-striated nascent myofibrils, but became apparent shortly after the development of compact Z-discs in early myotubes. Furthermore, we studied the expression of p0071 in a wide variety of neuromuscular disorders by indirect immunofluorescence. Here, the myofibrillar staining of p0071 was preserved in all the disease entities included in our study. Our results provide the first evidence that a member of the armadillo multigene family is a constituent of the contractile apparatus in human skeletal muscle. The localization of p0071 at the level of I-bands and the timepoint of its integration into developing myofibrils suggest a possible role in the organization of thin filaments. PMID- 11206136 TI - Proximo-distal organization and fibre type regionalization in rat hindlimb muscles. AB - Five muscles of the rat's lower hindlimb were compared with regard to their histochemical fibre type distribution at seven different proximo-distal levels. The muscles were: extensor digitorum longus (ED), flexor digitorum and hallucis longus (FD), gastrocnemius medialis (GM), peroneus longus (PE) and tibialis anterior (TA). In all the five muscles, the relative density of the 'slow' type I fibres showed a striking and similar decrease from proximal toward more distal levels. In addition, the type I fibres were concentrated within smaller and more eccentrically placed regions at distal than at more proximal levels. As a background for the further analysis of these lengthwise aspects of type I fibre regionalization, architectural features of the muscles were determined. Pinnation angles and the position of major tendons and tendon sheets were assessed in fresh specimens. Muscle fibre lengths were measured for single fibres dissected from different regions of macerated muscles. In all cases, fibre length was much shorter than muscle length (mean fraction ranging from 21 to 55%), implying that the proximo-distal changes in histochemical fibre properties were indeed explainable as being due to gradual lengthwise changes in fibre type populations. The similarity of these lengthwise changes across the muscles was in contrast to their differences in other aspects of functional organization, such as the average density of type I fibres and architectural features determining their relative capacities for shortening and force generation. The possible functional role of the proximal accumulation of type I fibres was discussed in relation to circulation and thermal balance; besides, the proximo-distal regionalization of type I fibres might (partly) reflect processes that had been associated with early stages of muscle differentiation. Furthermore, the results underline that, when determining the fibre type composition of rat hindlimb muscles, identifying the proximo-distal level of sampling is a matter of great importance. PMID- 11206137 TI - Translation is regulated via the 3' untranslated region of alpha-myosin heavy chain mRNA by calcium but not by its localization. AB - Posttranscriptional regulation plays an important role in alpha-myosin heavy chain (alpha-MyHC) protein synthesis in cardiac muscle cells. In the present study, we test the effects of calcium and mRNA mislocalization on alpha-MyHC translation in order to determine the mechanism(s) contributing to translational block via the 3' untranslated region (3'UTR). Neonatal rat cardiac myocytes were treated for 6 h with L-isoproterenol (10 microM) to enhance beating, with 10 microM verapamil to block beating and mislocalize mRNA, or with 3 microM colchicine to enhance beating but mislocalize mRNA by depolymerization of the microtubules. In order to determine whether translation is regulated by the 3'UTR, either a control (SV40 3'UTR) or the experimental (alpha-MyHC 3'UTR) was placed after a luciferase reporter gene and transfected into the myocytes. The amount of luciferase protein only decreased significantly in verapamil arrested cells transfected with the alpha-MyHC 3'UTR construct (P < 0.01). To control for the possibility that pharmacological treatments might affect transcription or message stability, we analyzed neomycin and luciferase mRNA levels transcribed from the same transfected plasmid. No significant changes were found with an RNase protection assay. These results suggest that calcium but not mRNA localization regulates protein synthesis and further, this is mediated by the 3' untranslated region of alpha-MyHC. PMID- 11206138 TI - Perturbation theory applied to sound propagation in flowing media confined by a cylindrical waveguide. AB - First-order perturbation theory is employed to examine sound propagation in flowing media confined by a cylindrical waveguide. The use of perturbation theory allows examination of mode phase-speed changes due to any radially dependent flow w(r) as long as the flow magnitude is sufficiently small. The condition to be fulfilled is satisfied in the flow range: 0-0.3 m/s for the specific values of cylinder radius, ultrasound frequency, and sound speed analyzed in the present work [in the general case, however, the condition in Eq. (1) of the present work must be fulfilled]. This freedom of choice, i.e., the possibility to handle any radial flow profile, is used to analyze two flow profile cases: (1) where w(r) is a linear combination of a laminar flow profile and a flat profile corresponding to turbulent flow, and (2) where w(r) is a linear combination of a laminar flow profile and a more realistic logarithmic-dependent turbulent flow profile. In both cases, it is shown that large errors may result in ultrasound flow measurements if several modes are excited by the transmitting transducer, and that a logarithmic flow profile in the turbulent regime leads to somewhat larger measurement errors at high flow values as compared to assuming a simple flat profile in the turbulent regime. PMID- 11206150 TI - Isolating the auditory system from acoustic noise during functional magnetic resonance imaging: examination of noise conduction through the ear canal, head, and body. AB - Approaches were examined for reducing acoustic noise levels heard by subjects during functional magnetic resonance imaging (fMRI), a technique for localizing brain activation in humans. Specifically, it was examined whether a device for isolating the head and ear canal from sound (a "helmet") could add to the isolation provided by conventional hearing protection devices (i.e., earmuffs and earplugs). Both subjective attenuation (the difference in hearing threshold with versus without isolation devices in place) and objective attenuation (difference in ear-canal sound pressure) were measured. In the frequency range of the most intense fMRI noise (1-1.4 kHz), a helmet, earmuffs, and earplugs used together attenuated perceived sound by 55-63 dB, whereas the attenuation provided by the conventional devices alone was substantially less: 30-37 dB for earmuffs, 25-28 dB for earplugs, and 39-41 dB for earmuffs and earplugs used together. The data enabled the clarification of the relative importance of ear canal, head, and body conduction routes to the cochlea under different conditions: At low frequencies (< or =500 Hz), the ear canal was the dominant route of sound conduction to the cochlea for all of the device combinations considered. At higher frequencies (>500 Hz), the ear canal was the dominant route when either earmuffs or earplugs were worn. However, the dominant route of sound conduction was through the head when both earmuffs and earplugs were worn, through both ear canal and body when a helmet and earmuffs were worn, and through the body when a helmet, earmuffs, and earplugs were worn. It is estimated that a helmet, earmuffs, and earplugs together will reduce the most intense fMRI noise levels experienced by a subject to 60-65 dB SPL. Even greater reductions in noise should be achievable by isolating the body from the surrounding noise field. PMID- 11206151 TI - Active noise control in a free field with virtual sensors. AB - The zone of local control around a "virtual energy density sensor" is compared with that offered by an actual energy density sensor, a single microphone, and a virtual microphone. Intended as an introduction to the concept of forward difference prediction and a precursor to evaluating the virtual sensor control algorithms in damped enclosures, this paper investigates an idealized scenario of a single primary sound source in a free-field environment. An analytical model is used to predict the performance of the virtual error sensors and compare their control performance with their physical counterparts. The model is then experimentally validated. The model shows that in general the virtual energy density sensor outperforms the actual energy density sensor, the actual microphone, and the virtual microphone in terms of centering a practically sized zone of local control around an observer who is remotely located from any physical sensors. However, in practice, the virtual sensor algorithms are shown to be sensitive (by varying degrees) to short wavelength spatial pressure variations of the primary and secondary sound fields. PMID- 11206152 TI - On the annoyance caused by impulse sounds produced by small, medium-large, and large firearms. AB - A laboratory study was designed in which the annoyance was investigated for 14 different impulse sound types produced by various firearms ranging in caliber from 7.62 to 155 mm. Sixteen subjects rated the annoyance for the simulated conditions of (1) being outdoors, and (2) being indoors with the windows closed. In the latter case, a representative outdoor-to-indoor reduction in sound level was applied. It was anticipated that the presumed additional annoyance caused by the "heaviness" of the impulse sounds might be predicted from the difference between the C-weighted sound exposure level (CSEL; LCE) and the A-weighted sound exposure level (ASEL; LAE). In the outdoor rating conditions, the annoyance was almost entirely determined by ASEL. The explained variance, r2, in the mean ratings by ASEL was 0.95. In the indoor rating conditions, however, the explained variance in the annoyance ratings by (outdoor) ASEL was significantly increased from r2 = 0.87 to r2= 0.97 by adding the product (LCE-LAE)(LAE-alpha) as a second variable. In combination with a 12-dB adjustment for small firearms, the present results showed that for the entire set of impulse sounds rated indoors with windows closed, the rating sound level, Lr, is given by Lr=LAE +12dB+beta(LCE LAE)(LAE-alpha), with alpha=45dB and beta=0.015dB(-1). For the outdoor rating condition, the optimal parameter values were equal to alpha=57 dB and, again, beta=0.015 dB(-1). In validation studies, in which the effects of the present rating procedure will be compared to field data, it has to be determined to what extent the constants alpha and beta have to be adjusted. PMID- 11206153 TI - Enhancing maximum measurable sound reduction index using sound intensity method and strong receiving room absorption. AB - The sound intensity method is usually recommended instead of the pressure method in the presence of strong flanking transmission. Especially when small and/or heavy specimens are tested, the flanking often causes problems in laboratories practicing only the pressure method. The purpose of this study was to determine experimentally the difference between the maximum sound reduction indices obtained by the intensity method, RI,max, and by the pressure method, Rmax. In addition, the influence of adding room absorption to the receiving room was studied. The experiments were carried out in an ordinary two-room test laboratory. The exact value of RI,max was estimated by applying a fitting equation to the measured data points. The fitting equation involved the dependence of the pressure-intensity indicator on measured acoustical parameters. In an empty receiving room, the difference between RI,max and Rmax was 4-15 dB, depending on frequency. When the average reverberation time was reduced from 3.5 to 0.6 s, the values of RI,max increased by 2-10 dB compared to the results in the empty room. Thus, it is possible to measure wall structures having 9-22 dB better sound reduction index using the intensity method than with the pressure method. This facilitates the measurements of small and/or heavy specimens in the presence of flanking. Moreover, when new laboratories are designed, the intensity method is an alternative to the pressure method which presupposes expensive isolation structures between the rooms. PMID- 11206154 TI - The prediction of speech intelligibility in underground stations of rectangular cross section. AB - Long enclosures are spaces with nondiffuse sound fields, for which the classical theory of acoustics is not appropriate. Thus, the modeling of the sound field in a long enclosure is very different from the prediction of the behavior of sound in a diffuse space. Ray-tracing computer models have been developed for the prediction of the sound field in long enclosures, with particular reference to spaces such as underground stations which are generally long spaces of rectangular or curved cross section. This paper describes the development of a model for use in underground stations of rectangular cross section. The model predicts the sound-pressure level, early decay time, clarity index, and definition at receiver points along the enclosure. The model also calculates the value of the speech transmission index at individual points. Measurements of all parameters have been made in a station of rectangular cross section, and compared with the predicted values. The predictions of all parameters show good agreement with measurements at all frequencies, particularly in the far field of the sound source, and the trends in the behavior of the parameters along the enclosure have been correctly predicted. PMID- 11206157 TI - The short-wave model and waves in two directions. AB - In the region where a sinusoidal wave in the cochlea reaches its maximum amplitude, the long-wave (or one-dimensional) model of the cochlea is deficient. In this region a short-wave model is more appropriate. However, in its current form, the short-wave model supports only waves in one direction. Therefore, it cannot cope with reflection effects associated with, e.g., inhomogeneities. Theoretical explorations of creation and internal reflection of otoacoustic emissions have almost exclusively been based on the long-wave model. In this article the road is paved for future explorations on a generalized form of the short-wave model, one that supports forward as well as backward waves, and thus can include internal reflections. PMID- 11206156 TI - Data processing options and response scoring for OAE-based newborn hearing screening. AB - Scoring of click-evoked otoacoustic emissions (CEOAEs) is typically achieved by the evaluation of the reproducibility of the whole emission and/or within narrow bands. Screening outcomes are influenced not only by the specific combination of the subdivision scheme (i.e., the number, position, and bandwidth of the narrow bands) and the threshold used to determine pass and refer, but also by the accuracy with which the reproducibility is estimated. This study was designed to examine what factors affect the accuracy of the reproducibility estimate and how the accuracy of the reproducibility estimate together with the choice of the subdivision scheme/thresholds affect CEOAE scoring. Simulations with real CEOAEs corrupted with synthesized noise indicated that the reproducibility estimate is influenced by time-windowing and band-pass filtering: the longer the time-window or the broader the bandwidth of the filter, the more accurate the estimate. Quantitative figures on numerical scoring were given in terms of the referral rate and were derived from CEOAEs recorded in a clinical environment from more than 3400 newborns. The narrow bands were extracted according to 12 different subdivision schemes covering the 1.5-4-kHz range. The referral rate was found to depend on the subdivision scheme being used: (i) the worst results were obtained considering four narrow bands at 1.6-2.4-3.2-4 kHz; (ii) the best results were obtained considering two narrow bands at 2.25 and 3.75 kHz; (iii) bandwidths greater than 1 kHz resulted in the lowest referral rates. Also, scoring based on the extraction of four narrow bands produced the most unstable results, i.e., a small change in the threshold might cause even a great change in the referral rate. PMID- 11206158 TI - Binaural coherence edge pitch. AB - The binaural coherence edge pitch (BICEP) is a dichotic broadband noise pitch effect similar to the binaural edge pitch (BEP). The BICEP stimulus is made by summing spectrally dense sine wave components with random phases. The interaural phase angle is a constant (0 or pi) for components with frequencies below (or above) a chosen edge frequency, and it is a random variable for the remaining components. The chosen edge frequency is a coherence edge because the noises to the two ears are mutually coherent within any band of frequencies on one side of the edge and they are mutually incoherent in any band on the other side. Pitch matching experiments show that the BICEP exists for coherence edge frequencies between about 300 and 1000 Hz. It is matched by a pure-tone frequency that differs from the edge frequency by 5% to 10%. The matching frequency lies on the incoherent side of the edge, an important result that is consistent with the way that the equalization-cancellation model has been applied to binaural pitch effects, especially the BEP. The results of BICEP experiments depend upon whether the coherent components are presented in 0 or pi interaural phase for some listeners but not for all. The BICEP persists if the noise to one of the ears is delayed, but it becomes weaker and less well matched as the delay increases beyond 2 ms. The BICEP does not depend on whether the component amplitudes are all created equal or are given a Rayleigh distribution. Some reliable pitch sensation exists even when the component amplitudes are entirely independent in the two ears, so long as the phase coherence conditions of the BICEP stimulus are maintained. The existence of the BICEP is a challenge for current models of dichotic pitch because none of them predicts all its features. PMID- 11206159 TI - A masking level difference due to harmonicity. AB - The role of harmonicity in masking was studied by comparing the effect of harmonic and inharmonic maskers on the masked thresholds of noise probes using a three-alternative, forced-choice method. Harmonic maskers were created by selecting sets of partials from a harmonic series with an 88-Hz fundamental and 45 consecutive partials. Inharmonic maskers differed in that the partial frequencies were perturbed to nearby values that were not integer multiples of the fundamental frequency. Average simultaneous-masked thresholds were as much as 10 dB lower with the harmonic masker than with the inharmonic masker, and this difference was unaffected by masker level. It was reduced or eliminated when the harmonic partials were separated by more than 176 Hz, suggesting that the effect is related to the extent to which the harmonics are resolved by auditory filters. The threshold difference was not observed in a forward-masking experiment. Finally, an across-channel mechanism was implicated when the threshold difference was found between a harmonic masker flanked by harmonic bands and a harmonic masker flanked by inharmonic bands. A model developed to explain the observed difference recognizes that an auditory filter output envelope is modulated when the filter passes two or more sinusoids, and that the modulation rate depends on the differences among the input frequencies. For a harmonic masker, the frequency differences of adjacent partials are identical, and all auditory filters have the same dominant modulation rate. For an inharmonic masker, however, the frequency differences are not constant and the envelope modulation rate varies across filters. The model proposes that a lower variability facilitates detection of a probe-induced change in the variability, thus accounting for the masked threshold difference. The model was supported by significantly improved predictions of observed thresholds when the predictor variables included envelope modulation rate variance measured using simulated auditory filters. PMID- 11206160 TI - Manipulating the "straightness" and "curvature" of patterns of interaural cross correlation affects listeners' sensitivity to changes in interaural delay. AB - The purpose of this study was to test the hypothesis that stimuli characterized by "straight" trajectories of their patterns of cross correlation foster greater sensitivity to changes in interaural temporal disparities (ITDs) than do stimuli characterized by more "curved" trajectories of their patterns of cross correlation. To do so, sensitivity to changes in ITD was measured, as a function of duration, using a set of "reference" stimuli that yielded differing relative amounts of straightness within their patterns of cross correlation while keeping the dominant trajectory at or near midline. The relative amounts of straightness were manipulated by employing specific combinations of bandwidth, ITD, and interaural phase disparity (IPD) of Gaussian noises centered at 500 Hz. The results were consistent with expectations in that the patterning of the threshold ITDs revealed increasingly poorer sensitivity as greater and greater curvature was imposed on the dominant, "midline," trajectory. The variations in threshold ITD across the stimulus conditions can be accounted for quite well quantitatively by assuming either that the listeners based their judgments on changes in the position of the most central peak of the cross-correlation function or that they based their judgments on changes in the centroid of a second-level cross correlation function. In a second experiment, binaural detection was measured using a subset of the reference stimuli as maskers. As expected, sensitivity was poorest with the maskers characterized by the greatest curvature, which were also those having the lowest interaural correlation. PMID- 11206162 TI - The influence of interaural stimulus uncertainty on binaural signal detection. AB - This paper investigated the influence of stimulus uncertainty in binaural detection experiments and the predictions of several binaural models for such conditions. Masked thresholds of a 500-Hz sinusoid were measured in an NrhoSpi condition for both running and frozen-noise maskers using a three interval, forced-choice (3IFC) procedure. The nominal masker correlation varied between 0.64 and 1, and the bandwidth of the masker was either 10, 100, or 1,000 Hz. The running-noise thresholds were expected to be higher than the frozen-noise thresholds because of stimulus uncertainty in the running-noise conditions. For an interaural correlation close to +1, no difference between frozen-noise and running-noise thresholds was expected for all values of the masker bandwidth. These expectations were supported by the experimental data: for interaural correlations less than 1.0, substantial differences between frozen and running noise conditions were observed for bandwidths of 10 and 100 Hz. Two additional conditions were tested to further investigate the influence of stimulus uncertainty. In the first condition a different masker sample was chosen on each trial, but the correlation of the masker was forced to a fixed value. In the second condition one of two independent frozen-noise maskers was randomly chosen on each trial. Results from these experiments emphasized the influence of stimulus uncertainty in binaural detection tasks: if the degree of uncertainty in binaural cues was reduced, thresholds decreased towards thresholds in the conditions without any stimulus uncertainty. In the analysis of the data, stimulus uncertainty was expressed in terms of three theories of binaural processing: the interaural correlation, the EC theory, and a model based on the processing of interaural intensity differences (IIDs) and interaural time differences (ITDs). This analysis revealed that none of the theories tested could quantitatively account for the observed thresholds. In addition, it was found that, in conditions with stimulus uncertainty, predictions based on correlation differ from those based on the EC theory. PMID- 11206163 TI - Investigation of the relationship among three common measures of precedence: fusion, localization dominance, and discrimination suppression. AB - Listeners have a remarkable ability to localize and identify sound sources in reverberant environments. The term "precedence effect" (PE; also known as the "Haas effect," "law of the first wavefront," and "echo suppression") refers to a group of auditory phenomena that is thought to be related to this ability. Traditionally, three measures have been used to quantify the PE: (1) Fusion: at short delays (1-5 ms for clicks) the lead and lag perceptually fuse into one auditory event; (2) Localization dominance: the perceived location of the leading source dominates that of the lagging source; and (3) Discrimination suppression: at short delays, changes in the location or interaural parameters of the lag are difficult to discriminate compared with changes in characteristics of the lead. Little is known about the relation among these aspects of the PE, since they are rarely studied in the same listeners. In the present study, extensive measurements of these phenomena were made for six normal-hearing listeners using 1-ms noise bursts. The results suggest that, for clicks, fusion lasts 1-5 ms; by 5 ms most listeners hear two sounds on a majority of trials. However, localization dominance and discrimination suppression remain potent for delays of 10 ms or longer. Results are consistent with a simple model in which information from the lead and lag interacts perceptually and in which the strength of this interaction decreases with spatiotemporal separation of the lead and lag. At short delays, lead and lag both contribute to spatial perception, but the lead dominates (to the extent that only one position is ever heard). At the longest delays tested, two distinct sounds are perceived (as measured in a fusion task), but they are not always heard at independent spatial locations (as measured in a localization dominance task). These results suggest that directional cues from the lag are not necessarily salient for all conditions in which the lag is subjectively heard as a separate event. PMID- 11206164 TI - Channel weights for speech recognition in cochlear implant users. AB - The purpose of this study was to develop and validate a method of estimating the relative "weight" that a multichannel cochlear implant user places on individual channels, indicating its contribution to overall speech recognition. The correlational method as applied to speech recognition was used both with normal hearing listeners and with cochlear implant users fitted with six-channel speech processors. Speech was divided into frequency bands corresponding to the bands of the processor and a randomly chosen level of corresponding filtered noise was added to each channel on each trial. Channels in which the signal-to-noise ratio was more highly correlated with performance have higher weights, and conversely, channels in which the correlations were smaller have lower weights. Normal hearing listeners showed approximately equal weights across frequency bands. In contrast, cochlear implant users showed unequal weighting across bands, and varied from individual to individual with some channels apparently not contributing significantly to speech recognition. To validate these channel weights, individual channels were removed and speech recognition in quiet was tested. A strong correlation was found between the relative weight of the channel removed and the decrease in speech recognition, thus providing support for use of the correlational method for cochlear implant users. PMID- 11206165 TI - Room reverberation effects in hearing aid feedback cancellation. AB - Room reverberation can affect feedback cancellation in hearing aids, with the strength of the effects depending on the acoustical conditions. These effects were studied using a behind the ear (BTE) hearing aid mounted on a dummy head and coupled to the ear canal via an open fitting. The hearing aid impulse response was measured for the dummy head placed at eight closely spaced locations in a typical office. The feedback cancellation in the hearing aid used a set of filter coefficients that were initialized for one location within the room, and then allowed to adapt to the feedback path measured at the same or to a different location. The maximum stable gain for the hearing aid was then estimated without feedback cancellation, for the initial set of feedback cancellation filter coefficients prior to adaptation, and for the feedback cancellation filter after adaptation. A low-order ARMA model combining a fixed set of poles with an adaptive FIR filter is shown to be effective in representing the feedback path exclusive of reverberation. Increasing the adaptive filter length has only a small benefit in improving the feedback cancellation performance due to the inability of the system to model the room reverberation. The mismatch between the modeled and actual feedback paths limits the headroom increase that can be achieved when using feedback cancellation, and varies with the location within the room. PMID- 11206166 TI - Recognition of time-distorted sentences by normal-hearing and cochlear-implant listeners. AB - This study evaluated the effects of time compression and expansion on sentence recognition by normal-hearing (NH) listeners and cochlear-implant (CI) recipients of the Nucleus-22 device. Sentence recognition was measured in five CI users using custom 4-channel continuous interleaved sampler (CIS) processors and five NH listeners using either 4-channel or 32-channel noise-band processors. For NH listeners, recognition was largely unaffected by time expansion, regardless of spectral resolution. However, recognition of time-compressed speech varied significantly with spectral resolution. When fine spectral resolution (32 channels) was available, speech recognition was unaffected even when the duration of sentences was shortened to 40% of their original length (equivalent to a mean duration of 40 ms/phoneme). However, a mean duration of 60 ms/phoneme was required to achieve the same level of recognition when only coarse spectral resolution (4 channels) was available. Recognition patterns were highly variable across CI listeners. The best CI listener performed as well as NH subjects listening to corresponding spectral conditions; however, three out of five CI listeners performed significantly poorer in recognizing time-compressed speech. Further investigation revealed that these three poorer-performing CI users also had more difficulty with simple temporal gap-detection tasks. The results indicate that limited spectral resolution reduces the ability to recognize time compressed speech. Some CI listeners have more difficulty with time-compressed speech, as produced by rapid speakers, because of reduced spectral resolution and deficits in auditory temporal processing. PMID- 11206167 TI - Phonetically trained models for speaker recognition. AB - In this paper, a speaker recognition system that introduces acoustic information into a Gaussian mixture model (GMM)-based recognizer is presented. This is achieved by using a phonetic classifier during the training phase. The experimental results show that, while maintaining the recognition rate, the decrease in the computational load is between 65% and 80% depending on the number of mixtures of the models. PMID- 11206168 TI - A linear relation between the compressibility and density of blood. AB - By considering the blood as a mixture of ultrafiltrate and protein concentrate, the additive nature of compressibility and density from the components is utilized to deduce a linear relation between the compressibility and density for blood. This deduction also indicates that the intercept and slope of the linear relation are independent of the hematocrit, plasma protein concentration, and hemoglobin concentration of red blood cells. To verify experimentally this linear relation, saline and plasma dilutions on porcine or canine blood flowing in an extracorporeal circuit were carried out. The hematocrit of the experiments ranges from 0% to 55% and the plasma protein concentration ranges from 10 to 90 g/l. A resonance device in the circuit measured the density rhob of blood at 37 degrees C and an ultrasound system measured the sound velocity cb. The range of density is from 1,010 to 1,060 g/l and that of sound velocity is from 1,530 to 1,580 m/s. The linear relation that best fits the data of compressibility [computed as (rhob cb(2))-1] and density has a correlation coefficient of 0.9978. The linear relation is found to fit well the dependence of compressibility on density derived from the sound velocity data of human, horse, and porcine blood in the literature. PMID- 11206170 TI - Whistles of boto, Inia geoffrensis, and tucuxi, Sotalia fluviatilis. AB - Whistles were recorded and analyzed from free-ranging single or mixed species groups of boto and tucuxi in the Peruvian Amazon, with sonograms presented. Analysis revealed whistles recorded falling into two discrete groups: a low frequency group with maximum frequency below 5 kHz, and a high-frequency group with maximum frequencies above 8 kHz and usually above 10 kHz. Whistles in the two groups differed significantly in all five measured variables (beginning frequency, end frequency, minimum frequency, maximum frequency, and duration). Comparisons with published details of whistles by other platanistoid river dolphins and by oceanic dolphins suggest that the low-frequency whistles were produced by boto, the high-frequency whistles by tucuxi. Tape recordings obtained on three occasions when only one species was present tentatively support this conclusion, but it is emphasized that this is based on few data. PMID- 11206174 TI - Effects of flanking component spectral position and modulation pattern on thresholds for signals presented in the peaks of a modulated tonal masker. PMID- 11206172 TI - Sound localization in a new-world frugivorous bat, Artibeus jamaicensis: acuity, use of binaural cues, and relationship to vision. AB - Passive sound-localization acuity and its relationship to vision were determined for the echolocating Jamaican fruit bat (Artibeus jamaicensis). A conditioned avoidance procedure was used in which the animals drank fruit juice from a spout in the presence of sounds from their right, but suppressed their behavior, breaking contact with the spout, whenever a sound came from their left, thereby avoiding a mild shock. The mean minimum audible angle for three bats for a 100-ms noise burst was 10 degrees-marginally superior to the 11.6 degrees threshold for Egyptian fruit bats and the 14 degrees threshold for big brown bats. Jamaican fruit bats were also able to localize both low- and high-frequency pure tones, indicating that they can use both binaural phase- and intensity-difference cues to locus. Indeed, their ability to use the binaural phase cue extends up to 6.3 kHz, the highest frequency so far for a mammal. The width of their field of best vision, defined anatomically as the width of the retinal area containing ganglion cell densities at least 75% of maximum, is 34 degrees. This value is consistent with the previously established relationship between vision and hearing indicating that, even in echolocating bats, the primary function of passive sound localization is to direct the eyes to sound sources. PMID- 11206175 TI - Sound source location by difference of phase, on a hydrophone array with small dimensions. PMID- 11206176 TI - A large-aperture array of nonlinked receivers for acoustic positioning of biological sound sources. PMID- 11206182 TI - Acoustic waveform inversion with application to seasonal snow covers. AB - The amplitude and waveform shape of atmospheric acoustic pulses propagating horizontally over a seasonal snow cover are profoundly changed by the air forced into the snow pores as the pulses move over the surface. This interaction greatly reduces the pulse amplitude and elongates the waveform compared to propagation above other ground surfaces. To investigate variations in snow-cover effects, acoustic pulses were recorded while propagating horizontally over 11 different naturally occurring snow covers during two winters. Two inversion procedures were developed to automatically match the observed waveforms by varying the snow-cover parameters in theoretical calculations. A simple frequency-domain technique to match the dominant frequency of the measured waveform suffered from multiple solutions and poor waveform matching, while a time-domain minimization method gave unique solutions and excellent waveform agreement. Results show that the effective flow resistivity and depth of the snow are the parameters controlling waveform shape, with the pore shape factor ratio of secondary importance. Inversion estimates gave flow resistivities ranging from 11 to 29 kN s m(-4), except for two late-season cases where values of 60 and 140 were determined (compared to 345 for the vegetation-covered site in the summer). Acoustically determined snow depths agreed with the measured values in all but one case, when the depth to a snow layer interface instead of the total snow depth was determined. Except for newly fallen snow, the pore shape factor ratio values clustered near two values that appear to correspond to wet (1.0) or dry (0.8) snow. PMID- 11206183 TI - Antagonistic effects of selective alpha1-adrenoceptor antagonists MDL73005EF and tamsulosin and partial agonists clonidine and tizanidine in rat thoracic aorta and rabbit iliac artery. AB - The antagonistic effects of MDL73005EF and tamsulosin and partial agonists clonidine and tizanidine at rat thoracic aorta and rabbit iliac artery alpha1 adrenoceptors were investigated in this study. Selective alpha1-adrenoceptor antagonists MDL73005EF and tamsulosin dose-dependently shifted the concentration response curves for noradrenaline to the right. Schild plots of the results obtained from the inhibition by MDL73005EF (pA2 8.30 +/- 0.04) and tamsulosin (pA2 10.51 +/- 0.06) of noradrenaline yielded a straight line with a slope of unity in rat thoracic aorta. The slopes of Schild plots obtained from the inhibition by MDL73005EF and tamsulosin of noradrenaline were significantly different from unity in rabbit iliac artery. Schild plots of the results obtained from the inhibition by clonidine and tizanidine of noradrenaline yielded a straight line with a slope of unity in rat thoracic aorta (pA2 7.08 +/- 0.04 and 7.32 +/- 0.04, respectively). These results suggest that alpha1D-adrenoceptors play a significant role in the alpha1-adrenoceptor-agonist-induced contraction of rat thoracic aorta and rabbit iliac artery, and that clonidine and tizanidine interact with the alpha1D-adrenoceptor subtype as competitive antagonists in rat thoracic aorta. PMID- 11206184 TI - Enhanced nasal retention of hydrophobically modified polyelectrolytes. AB - Hydrophobically modified polyelectrolytes (HMP) are polymers with a high content of ionizable groups bonded to hydrophobic groups. Copolymers of poly(acrylic acid) and Pluronic surfactants constitute a special class of HMP whereby poly(propylene oxide) segments act as hydrophobes. The poly(propylene oxide) segments possess temperature-dependent aqueous solubility and the solutions of the Pluronic-poly(acrylic acid) copolymers (MW > 3,000,000) undergo a sol-gel transition when kept at body temperature. Due to the presence of the poly(acrylic acid) segments, the Pluronic-poly(acrylic acid) copolymers are bioadhesive. We have examined the hypothesis that the in-situ gelling polymer formulations of Pluronic-poly(acrylic acid) copolymers may have an enhanced retention in the nasal cavity. The effects of putative bioadhesive (Carbomer 934P) and thermogelling (Pluronic F127) polymers on nasal clearance were compared with Pluronic-poly(acrylic acid) copolymers using a rat model. The enhancement of the residence time of fluorescent labels by the Pluronic-poly(acrylic acid) copolymers was shown to be 5-8-fold that of Carbomer, and 3-6-fold that of Pluronic F127. The results unequivocally demonstrate the superior retention of the HMP that combines bioadhesive and thermogelling capabilities over either a bioadhesive polyelectrolyte or a polymer of a low molecular weight that undergoes a sol-gel transition. PMID- 11206185 TI - Reduction of structural perturbations in bovine serum albumin by non-aqueous microencapsulation. AB - Protein stability is a factor limiting the use of sustained-release devices in medical applications. The aim of this study was to reduce structural perturbations occurring in the frequently used model protein, bovine serum albumin (BSA), upon microencapsulation in poly(D,L-lactide-co-glycolide) (PLG) microspheres. Spray freeze-dried BSA was encapsulated into PLG microspheres by a completely non-aqueous oil-in-oil encapsulation procedure. FTIR spectroscopy was used as a non-invasive method to quantify procedure-induced structural perturbations in BSA. Spray-freeze drying of BSA caused significant structural perturbations that were minimized by co-spray freeze-drying BSA with trehalose. BSA-containing microspheres were produced by suspension of the powder by homogenization in methylene chloride containing PLG, followed by formation of coacervate droplets by the addition of silicon oil and hardening using the solvent heptane. Resulting microspheres had dimensions of approximately 100 microm and the encapsulation efficiency for BSA was > 90%. FTIR data showed that the structure of the BSA-trehalose formulation encapsulated into PLG microspheres was less perturbed than that of BSA obtained from buffer alone. The results demonstrate that the structure-guided encapsulation approach introduced for non aqueous casting encapsulation procedures can be extended to the non-aqueous production of pharmaceutically relevant PLG microspheres involving a complex encapsulation procedure. PMID- 11206186 TI - Biphasic effects of acetaldehyde-biogenic amine condensation products on membrane fluidity. AB - I have studied the effects of four acetaldehyde-biogenic amine condensation products on membrane fluidity of liposomes, consisting of 1-palmitoyl-2 oleoylphosphatidylcholine and cholesterol, by measuring fluorescence polarization using different probes. The condensation products were 1-methyl-1,2,3,4 tetrahydro-beta-carboline (MTBC), 6-hydroxy-1-methyl-1,2,3,4-tetrahydro-beta carboline (6-OH-MTBC), 3-carboxy-1-methyl-1,2,3,4-tetrahydro-beta-carboline (3-C MTBC) and 6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoline (salsolinol). They changed the fluidity of the hydrophobic and hydrophilic regions of liposomal membranes at micromolar levels almost corresponding to their antibacterial and antiplatelet concentrations, but their membrane effects varied by structure, concentration and membrane lipid composition. MTBC and salsolinol showed biphasic effects on the inner layers of membranes to enhance the fluidity at 250-1000 microM and reduce the fluidity at 50-100 microM, whereas both of them fluidized the outer layers of the membranes. 3-C-MTBC concentration-dependently fluidized both layers of membranes. 6-OH-MTBC most weakly enhanced and reduced the fluidity of the outer and inner layers, respectively. The membrane effect of MTBC was the greatest of the four condensation products. MTBC (50-1000 nM) significantly reduced the fluidity by exclusively acting on the membrane core, but was less effective in fluidizing the membrane surface. However, the others were not active at low nanomolar levels. The membrane effects may be partly responsible for the antibacterial and antiplatelet actions of the acetaldehyde-biogenic amine condensation products, although they do not appear to be simple membrane fluidizers. PMID- 11206187 TI - Vancomycin resistance reversal in enterococci by flavonoids. AB - The development of clinical vancomycin-resistant strains of enterococci (VRE) is a major cause for concern. Here we show that a combination of galangin or 3,7 dihydroxyflavone with vancomycin may be used to sensitize resistant strains of Enterococcus faecalis and Enterococcus faecium to the level of vancomycin sensitive strains. Minimum inhibitory concentrations (MICs) and viable counts were determined in Iso-sensitest broth using a microtitre method. MICs of vancomycin against 67% of resistant clinical isolates and a type strain of enterococci were lowered from > 250 microg mL(-1) to < 4 microg mL(-1) in the presence of galangin (12.5 microg mL(-1)) or 3,7-dihydroxyflavone (6.25 microg mL(-1)). Viable counts for type culture E. faecalis ATCC 51299 showed the flavonoids alone significantly lowered numbers of colony forming units (CFUs). CFUs were maintained at low levels (< 10(3) CFU mL(-1)) for 24 h by vancomycin/flavone combinations. This combinational action in reversing vancomycin resistance of enterococci highlights novel drug targets and has importance in the design of new therapeutic regimes against resistant pathogens. PMID- 11206189 TI - The biopharmaceutical aspects of nasal mucoadhesive drug delivery. AB - Nasal drug administration has frequently been proposed as the most feasible alternative to parenteral injections. This is due to the high permeability of the nasal epithelium, allowing a higher molecular mass cut-off at approximately 1000 Da, and the rapid drug absorption rate with plasma drug profiles sometimes almost identical to those from intravenous injections. Despite the potential of nasal drug delivery, it has a number of limitations. In this review, the anatomy and physiology of the nasal cavity, as well as ciliary beating and mucociliary clearance as they relate to nasal drug absorption, are introduced. The rationale for nasal drug delivery and its limitations, some factors that influence nasal drug absorption, and the experimental models used in nasal drug delivery research are also reviewed. Nasal mucoadhesion as a promising method of nasal absorption enhancement is discussed, and factors that influence mucoadhesion, as well as safety of nasal mucoadhesive drug delivery systems are reviewed in detail. Nasal drug administration is presently mostly used for local therapies within the nasal cavity. Anti-allergic drugs and nasal decongestants are the most common examples. However, nasal drug administration for systemic effects has been practised since ancient times. Nasally-administered psychotropic drugs by native Americans, the use of tobacco snuffs, and nasal administration of illicit drugs such as cocaine are all well known (Illum & Davis 1992). Nowadays, the nasal cavity is being actively explored for systemic administration of other therapeutic agents, particularly peptides and proteins (Illum 1992; Edman & Bjork 1992), as well as for immunization purposes (Lemoine et al 1998). To better understand the basis for nasal drug absorption and factors that can influence it, a brief review of the anatomy and physiology of the nose is appropriate. PMID- 11206188 TI - Formulation and release characteristics of poly(lactic-co-glycolic acid) microspheres containing chemically modified protein. AB - Chemical modification of proteins may influence their formulation into and release from polymeric microspheres. Three chemical modifications of rat serum albumin (RSA) were effected on the amine groups of this protein: conjugation with a polyanion using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide, intermolecular cross-linking using glutaraldehyde, and reductive alkylation using propyl aldehyde. The modified proteins had different physicochemical properties as well as improved encapsulation efficiencies compared with native RSA microspheres. The microspheres were incubated at 37 degrees C for over one month to investigate the influence of protein modification on the release profiles. Microsphere degradation accelerated from the ninth day of the release studies and this coincided with an increase in the release rates. The degradation rates of poly(lactic-co-glycolic acid) microspheres containing either native or cross linked RSA were more rapid than those containing either heparin conjugated or propylated RSA. This was in agreement with the release data, since the release of the native and cross-linked RSA were more rapid than those of the other modified proteins. The release profiles of the RSA-heparin conjugates and the propylated RSA were approximately zero rather than first order between the tenth and thirtieth day of study. Chemical modification of protein may be a useful method to increase encapsulation efficiency and to decrease release rates of proteins that are to be used in microsphere formulations of potent therapeutic proteins. PMID- 11206190 TI - Gastrointestinal transit of dosage forms in the pig. AB - The gastrointestinal transit of liquid, pellet and tablet formulations was measured under fasted conditions in the domestic pig (n = 4) using the technique of gamma scintigraphy. The mean times for 50% gastric emptying for liquid and pellet systems were 1.4 and 2.2 h, respectively; tablets emptied between 1.5 and 6.0 h. Total transit times were in the order of 50 h. These data conform well to published values for the transit of liquid and solid food materials in the pig. The times are much shorter than those previously published for the transit of solid dosage forms in the pig. We conclude that the domestic pig would be a good model to study the gastrointestinal transit of pharmaceutical formulations and the absorption of drug compounds. PMID- 11206191 TI - An investigation into the thermal behaviour of an amorphous drug using low frequency dielectric spectroscopy and modulated temperature differential scanning calorimetry. AB - The objective of the study was to investigate the use of low frequency dielectric spectroscopy as a means of characterizing the thermal transitions of an amorphous drug substance, indometacin, with particular emphasis on modelling the response using the Dissado-Hill function. The low frequency dielectric behaviour of indometacin was measured over a temperature range of 10-160 degrees C and a frequency range of 10(-3)-10(6) Hz. Modulated temperature differential scanning calorimetry (MTDSC) studies were also performed on equivalent samples, showing a glass transition, recrystallization and melting. Isothermal low frequency dielectric spectra of the sample at temperatures below recrystallization showed the dynamic dielectric relaxation associated with the amorphous phase, while changes in the real and imaginary permittivities were observed that were associated with recrystallization and subsequent melting. A small discontinuity was observed immediately above the recrystallization process in the MTDSC and dielectric data, suggested to correspond to a solid state transformation. The use of the Dissado-Hill function as a means of modelling the dielectric behaviour has also been described. The study suggests that low frequency dielectric spectroscopy, used in conjunction with MTDSC and Dissado-Hill modelling, may be a useful tool for the characterization of amorphous and crystalline drugs. PMID- 11206192 TI - Effect of FITC-dextran molecular weight on its release from floating cetyl alcohol and HPMC tablets. AB - The release mechanism of high molecular weight fluorescein isothiocyanate dextrans (FITC-dextrans) from HPMC hydrogel matrices was studied. An anomaly was noted in the release behaviour of a series of high molecular weight FITC-dextrans from a tablet formulation designed to float in stomach contents. The tablets contained sodium bicarbonate and hydroxypropylmethyl cellulose (HPMC) in a cetyl alcohol matrix. When hydrated in an acid medium, this tablet consisted of a mixed solid with a viscous surface layer containing carbon dioxide bubbles through which the active ingredient (FITC-dextran) was released into the aqueous environment. However, it was observed that, above a critical molecular weight (approx. 65 kDa), the FITC-dextran was only released into the medium by an erosion-type mechanism, whereas, below this value, both diffusion and erosion processes took place. The key constraint appeared to be the apparent gel pore size of the hydrated HPMC that was approximately 12 nm in diameter, irrespective of the molecular weight of the HPMC samples evaluated. It was concluded that FITC dextran release was controlled by both FITC-dextran molecular weight and the HPMC hydrogel structure. PMID- 11206193 TI - Microparticulate uptake mechanisms of in-vitro cell culture models of the respiratory epithelium. AB - The objective of this study was to examine the uptake mechanisms of fluorescent polystyrene microspheres of various diameters and surface chemistry by two human cell lines derived from the respiratory epithelium, A549 and Calu-3. Briefly, A549 and Calu-3 cells were grown to confluence in 12-well cluster plates and the uptake of fluorescent microspheres by the cells was determined at various time points. The amount of microspheres internalized by the cells was determined by correcting for non-specific binding to the cell surface. The data showed that A549 cells appeared to have more phagocytic activity than Calu-3 cells. Albumin coated microspheres as large as 3 microm diameter can be internalized by A549 cells. The amount of internalization by A549 cells observed for 0.5-microm diameter albumin-coated microspheres was approximately 10-times greater than that observed for 1-microm diameter spheres and approximately 100-times greater than values observed for 2- and 3-microm diameter beads. Transmission electron micrographs confirmed that the microspheres were internalized by the cells. Uptake experiments conducted with Calu-3 cells indicated that albumin-coated microspheres were neither bound nor internalized by the cells. The effect of microsphere surface chemistry on the uptake mechanism indicated that amidine microspheres were internalized more rapidly and to a greater extent by both A549 and Calu-3 cells than carboxylate microspheres and non-coated microspheres. This phenomenon is thought to be attributed to masking of the negative polystyrene core by the positive amidine functional group; this effect was less marked for the carboxylate microspheres. These results suggest that A549 and Calu-3 cells can internalize microspheres and that size and effective charge played an important role in the uptake process. PMID- 11206194 TI - Pharmacokinetics and bioavailability of alpha-, gamma- and delta-tocotrienols under different food status. AB - We have investigated the pharmacokinetics and bioavailability of alpha-, gamma- and delta-tocotrienols under fed and fasted conditions in eight healthy volunteers. The volunteers were administered a single oral dose of mixed tocotrienols (300 mg) under fed or fasted conditions. The bioavailability of tocotrienols under the two conditions was compared using the parameters peak plasma concentration (Cmax), time to reach peak plasma concentration (Tmax) and total area under the plasma concentration-time curve (AUC(o-infinity)). A statistically significant difference was observed between the fed and fasted logarithmic transformed values of Cmax (P < 0.01) and AUC(0-infinity) (P < 0.01) for all three tocotrienols. In addition, the 90% confidence intervals for the ratio of the logarithmic transformed AUC(0-infinity) values of alpha-, gamma- and delta-tocotrienols under the fed state over those of the fasted state were found to lie between 2.24-3.40, 2.05-4.09 and 1.59-3.81, respectively, while those of the Cmax were between 2.28-4.39, 2.31-5.87 and 1.52-4.05, respectively. However, no statistically significant difference was observed between the fed and fasted Tmax values of the three homologues. The mean apparent elimination half-life (t(1/2)) of alpha-, gamma- and delta-tocotrienols was estimated to be 4.4, 4.3 and 2.3 h, respectively, being between 4.5- to 8.7-fold shorter than that reported for alpha-tocopherol. No statistically significant difference was observed between the fed and fasted t(1/2) values. The mean apparent volume of distribution (Vd/f) values under the fed state were significantly smaller than those of the fasted state, which could be attributed to increased absorption of the tocotrienols in the fed state. PMID- 11206195 TI - Secretory transport of p-aminohippuric acid across intestinal epithelial cells in Caco-2 cells and isolated intestinal tissue. AB - The intestinal transport of an organic anion, p-aminohippuric acid (PAH), was studied in Caco-2 cell monolayers and rat intestinal tissue mounted in Ussing chambers. In both experimental methods, PAH exhibited vectorial transport with significantly greater permeability in the secretory direction than the absorptive direction, indicating net secretion. This secretory transport required metabolic energy, but protons or hydroxyl ions were not involved as the driving force. In Caco-2 monolayers, secretory transport of [3H]PAH was decreased, and the intracellular accumulation of PAH was increased with increasing concentration of unlabelled PAH at the basolateral side. Addition of probenecid and genistein at the basolateral side decreased the secretory transport of [3H]PAH; the accumulation was not changed by probenecid, but was increased by genistein. In addition, the initial uptake rate of [3H]PAH from the basolateral side was decreased by both PAH and probenecid, but not by genistein. Therefore, it is suggested that the transport of PAH in Caco-2 cells is regulated by several transporters: a genistein-sensitive transporter on the apical membrane and probenecid-sensitive transporters on both the basolateral and apical membranes. In rat intestinal tissues, the transport rate of PAH showed regional variation (ileum > jejunum > duodenum), suggesting that secretory transporters with high activity exist predominantly in the lower region of the small intestine. The results suggest that PAH transport in both Caco-2 cells and rat intestinal tissues is regulated by multiple transporters on the apical and basolateral membranes, and these transporters have different characteristics. PMID- 11206196 TI - Synthesis and in-vitro anticancer evaluation of bis-tacrine congeners. AB - In the search for potential new anticancer drugs, an efficient synthesis of bis tetrahydroaminoacridine (bis-tacrine) and its congeners was accomplished by bis amination of 9-chlorotetrahydroacridine and its congeners under heated conditions. The critical chlorides were efficiently prepared from o-aminoaromatic acids and cycloketones in-situ in the presence of phosphorus oxychloride. In vitro cytotoxic evaluation of the compounds was carried out against a panel of 60 human cancer cell lines. Among them, butyl-linked bis-tacrine (5b) exhibited the strongest cytotoxic profile with GI50 (concentration causing 50% growth inhibition) values of approximately 0.04-0.08 microM against breast, colon, melanoma and non-small lung cancer cells. Congeners bearing a longer alkyl chain were on average 30- to 100-fold less cytotoxic against these cancer cells. Shorter connecting alkyl chains of bis-tacrine or its congeners dramatically decreased the cytotoxic effects. Compound 5b has been selected for further biological evaluation of its anticancer profile. PMID- 11206197 TI - Potential transition state phosphoramidate inhibitors of beta-tubulin as antifilarial agents. AB - Transition state phosphoramidate inhibitors of beta-tubulin were designed as potential antifilarial agents. The reaction of 2-aminobenzimidazole with diisopropyl phosphite and carbon tetrachloride at a low temperature gave the unexpected 1-diisopropoxyphosphoryl-2-aminobenzimidazole, which on heating gave the novel benzimidazole derivative, 2-(diisopropoxyphosphoryl)aminobenzimidazole. Both products were fully characterized and the synthetic procedure to both compounds was optimized. The procedure was used to prepare the related 5-benzoyl 2-(diisopropoxyphosphoryl)aminobenzimidazole and 5-benzoyl-2 (diethoxyphosphoryl)aminobenzimidazole (1d). In a preliminary trial against Brugia pahangi compound 1d was found to have no antifilarial activity. This lack of activity may be attributed to its extreme insolubility and thus low bioavailability. The synthesis of analogous, more soluble, phosphorothioate substituted benzimidazoles using the same methods may yield compounds with greater antifilarial activity. PMID- 11206198 TI - A near-infrared method for the assay of cineole in eucalyptus oil as an alternative to the official BP method. AB - Thirty different eucalyptus oil samples were scanned on the FOSS NIRSystems 6500 Rapid Content Sampler using a reflectance vessel as sample presentation method. The cineole content of each sample was determined by the BP method and these reference data were used to construct two calibration equations for cineole content in the oils using Vision software. The mean accuracy for the NIR method differed by 1.01% or less, and the mean bias by +/-0.33% or less, compared with the BP method. Calculation of the 95% confidence intervals for the slope and intercept of plots of NIR predicted values against BP method reference values showed that there was no evidence of fixed or relative systematic errors. Tests for short-term and intermediate repeatability were conducted. The standard deviation was 0.83% w/w or less and the coefficient of variation was 1.11% or less. The confidence intervals for both short-term and intermediate repeatability overlapped with that for the BP method, suggesting that there was no evidence for a difference in values obtained by the BP and NIR methods. The range of cineole contents used in the calibrations was extended by incorporating five samples of eucalyptus oil spiked with cineole, and five samples of two essential oils known to have a lower cineole content than eucalyptus oil, to give a range of 52.5 to 99.0% w/w. The mean accuracy decreased to an error of 1.26% or less and the bias to +/-0.50% or less. Again, confidence intervals suggested there was no evidence for fixed or systematic errors in the NIR calibrations. We propose that NIR spectroscopy could be used as an alternative method for the determination of cineole content in eucalyptus oils. PMID- 11206199 TI - Properties of inductive reasoning. AB - This paper reviews the main psychological phenomena of inductive reasoning, covering 25 years of experimental and model-based research, in particular addressing four questions. First, what makes a case or event generalizable to other cases? Second, what makes a set of cases generalizable? Third, what makes a property or predicate projectable? Fourth, how do psychological models of induction address these results? The key results in inductive reasoning are outlined, and several recent models, including a new Bayesian account, are evaluated with respect to these results. In addition, future directions for experimental and model-based work are proposed. PMID- 11206200 TI - Dual processes in recognition: does a focus on measurement operations provide a sufficient foundation? AB - Current theoretical thinking about dual processes in recognition relies heavily on the measurement operations embodied within the process dissociation procedure. We critically evaluate the ability of this procedure to support this theoretical enterprise. We show that there are alternative processes that would produce a rough invariance in familiarity (a key prediction of the dual-processing approach) and that the process dissociation procedure does not have the power to differentiate between these alternative possibilities. We also show that attempts to relate parameters estimated by the process dissociation procedure to subjective reports (remember-know judgments) cannot differentiate between alternative dual-processing models and that there are problems with some of the historical evidence and with obtaining converging evidence. Our conclusion is that more specific theories incorporating ideas about representation and process are required. PMID- 11206201 TI - The ties that bind what is known to the recall of what is new. AB - Cued recall success varies with what people know and with what they do during an episode. This paper focuses on prior knowledge and disentangles the relative effects of 10 features of words and their relationships on cued recall. Results are reported for correlational and multiple regression analyses of data obtained from free association norms and from 29 experiments. The 10 features were only weakly correlated with each other in the norms and, with notable exceptions, in the experiments. The regression analysis indicated that forward cue-to-target strength explained the most variance, followed by backward target-to-cue strength. Target connectivity and set size explained the next most variance, along with mediated cue-to-target strength. Finally, frequency, concreteness, shared associate strength, and cue set size also contributed significantly to recall. Taken together, indices of prior word knowledge explain 49% of the recall variance. Theoretically driven equations that use free association to predict cued recall were also evaluated. Each equation was designed to condense multiple indices of word interconnectivity into a single predictor. PMID- 11206202 TI - Semantic priming without association: a meta-analytic review. AB - A meta-analysis of 26 studies indicated that automatic semantic priming can occur without association. Priming did not vary substantially with differences in variables that affect automatic versus strategic processing, such as time spent processing the prime and target, relationship proportion, and task (except that average effects were smaller in the naming task). Although category coordinates were investigated in the majority of studies, synonyms, antonyms, and script relations also demonstrated priming; functional relations showed greater priming, and essential and perceptual relations showed less. The average effect size for semantic priming was smaller than that for associative priming, suggesting that there is an "associative boost" from adding an associative relationship to a semantic one. The implications of these findings for the modularity thesis and for models of semantic priming are discussed. PMID- 11206203 TI - Demonstration of a socially transmitted flavor aversion in rats? Kuan and Colwill (1997) revisited. AB - In each of three experiments that differed only in procedural detail, observer rats interacted with pairs of conspecific demonstrators, one fed a cocoa-flavored diet (Diet Coc) and the other a cinnamon-flavored diet (Diet Cin). Immediately after both members of a pair of demonstrators had been fed, and 5 min before they interacted with an observer or observers, one of the demonstrators was made ill by intraperitoneal injection with lithium chloride. After interacting with a pair of demonstrators for 15 min, each observer was allowed to choose between Diet Cin and Diet Coc for 22 h. In all three experiments, observer rats consumed as much Diet Cin after interacting simultaneously with both an ill demonstrator that had eaten Diet Cin and a healthy demonstrator that had eaten Diet Coc as after interacting simultaneously with both a healthy demonstrator that had eaten Diet Cin and an ill demonstrator that had eaten Diet Coc. These results raise questions about the generality of Kuan and Colwill's (1997) demonstration of socially transmitted flavor aversions in Norway rats. PMID- 11206204 TI - Blocking and backward blocking involve learned inattention. AB - Four experiments examine blocking of associative learning by human participants in a disease diagnosis procedure. The results indicate that after a cue is blocked, subsequent learning about the cue is attenuated. This attenuated learning after blocking is obtained for both standard blocking and for backward blocking. Attenuated learning after blocking cannot be accounted for by theories such as the Rescorla-Wagner model that rely on lack of learning about a redundant cue, nor can it be accounted for by extensions of the Rescorla-Wagner model designed to address backward blocking that encode absent cues with negative values. The results are predicted by the hypothesis that people learn not to attend to the blocked cue. PMID- 11206205 TI - Attentional requirements for object-location priming. AB - The purpose of the present experiments was to investigate whether a verbal and a spatial secondary task would disrupt priming for object-location associations. Symbols were placed one at a time in one of nine locations in a rectangle. Implicit memory was tested with a reaction time (RT) task. All symbols were placed in the same location of the rectangle across 10 trial blocks; then, all their locations were changed. Responses were made on the numeric keypad, which corresponded to the spatial locations used in the rectangle. A decrease in RTs across the first 10 trial blocks followed by an increase in RTs when the symbols changed locations would indicate priming for the associations. The results were that implicit memory for object-location associations was obtained under single-, but not under dual-task conditions. We have interpreted the results in terms of a working memory model that posits that implicit memory will suffer when cognitive resources are limited. PMID- 11206207 TI - Testing the counter model for perceptual identification: effects of repetition priming and word frequency. AB - The counter model for perceptual identification (Ratcliff & McKoon, 1997) differs from alternative views of word recognition in two important ways. First, it assumes that prior study of a word does not result in increased sensitivity but, rather, in bias. Second, the effects of word frequency and prior study are explained by different mechanisms. In the present experiment, study status and word frequency of target and foil were varied independently. Using a forced choice task, we replicated the bias effect. However, we also found several interactions between frequency and prior study that are in direct conflict with the counter model. Most important, prior study of both alternatives resulted in an attenuation of the frequency effect and an increase in performance for low frequency targets, but not for high-frequency targets. These findings suggest that the effects of frequency and prior study are not mediated by completely independent mechanisms. PMID- 11206206 TI - Mental rotation is suppressed during saccadic eye movements. AB - We examined whether mental rotation is suppressed during saccadic eye movements. Subjects judged whether a character was normal or mirror-reversed while making no, short, or long saccades. Reaction time was longer under saccade than under no saccade conditions and was longer when a long saccade rather than a short saccade was made, but only when the characters varied in orientation. These results indicate that mental rotation is suppressed during saccadic eye movements. The implications for theories of cognitive suppression during saccades are discussed. PMID- 11206208 TI - Repetition and form priming interact with neighborhood density at a brief stimulus onset asynchrony. AB - The relationships between repetition- and form-priming effects and neighborhood density were analyzed in two masked priming experiments with the lexical decision task. Given that form-priming effects appear to be influenced by a word's orthographic neighborhood, it is theoretically important to find out whether repetition priming also differs as a function of the word's orthographic neighborhood. Within an activation framework, repetition- and form-priming effects are just quantitatively different phenomena, whereas the two effects are qualitatively different in a serial-ordered model of lexical access (the entry opening model). The results show that repetition- and form-priming effects were stronger for hermit words than for words with many neighbors. These results pose some problems for both activation and serial-ordered models. The implications of these results for determining how neighbors affect the identification of a word are discussed. PMID- 11206209 TI - Stroop effect in words that differ from color words in one letter only. AB - In two experiments, participants named the color of a colored word, which was a Hebrew color word or a word in Hebrew that was different from a color word in one letter only. The magnitude of the Stroop effect increased with the location of the changed letter. It was smallest when the first letter of the color word was replaced, resulting in a noncolor word, and it was largest when the last letter was replaced. These results challenge the assumption that automatic reading, as indicated by the Stroop effect, can be explained exclusively by memory retrieval accounts of automaticity. The results also have implications for the sources of facilitation and inhibition in the Stroop effect. PMID- 11206210 TI - Estimating the frequency of nonevents: the role of recollection failure in false recognition. AB - Participants studied lists of multiply presented converging associates (e.g., bed, dream, pillow, etc.) and were timed as they estimated how often they saw list items, related foils (e.g., blanket), and nonpresented critical items (SLEEP). Average number of repetitions (few [3] vs. many [6]) and repetition variability (fixed vs. variable) were manipulated between subjects. Participants responded more slowly to critical items (3.18 sec) than to list items (2.45 sec) or foils (2.22 sec). In addition, critical-item judgments of frequency (JOFs) were about as large as list-item JOFs, and false recognition (i.e., nonzero JOFs) of critical items was most likely in the few-fixed condition (96%) and least likely in the many-fixed condition (74%). These findings suggest that people can use recollection failure--the absence of an anticipated recollective experience, coupled with strong familiarity--to distinguish critical items from list items and that recollection failure is weighted most heavily when people expect familiar probes to access episodic information. PMID- 11206211 TI - Adults' strategy choices for simple addition: effects of retrieval interference. AB - Simple addition (e.g., 3 + 2, 7 + 9) may be performed by direct memory retrieval or by such procedures as counting or transformation. The distribution of associations (DOA) model of strategy choice (Siegler, 1988) predicts that procedure use should increase as retrieval interference increases. To test this, 100 undergraduates performed simple addition problems, either after blocks of simple multiplication (high-interference context) or after blocks of simple division problems (low-interference context). Addition took longer and was more error prone after multiplication; in particular, there were more multiplication confusion errors on the relatively easy, small-number addition problems (e.g., 3 + 2 = 6, 4 + 3 = 12), but not on the more difficult, large-number additions. Consistent with the DOA, participants reported greater use of procedures for addition after multiplication, but more so for small addition problems. The findings demonstrate that adults' use of procedural strategies for simple addition is substantially influenced by retrieval interference. PMID- 11206212 TI - Depictions of motion devised by a blind person. AB - A blind man (E.A.) was asked to draw pictures suggesting wheels in various kinds of motion. Six pictures were drawn by E.A. The pictures were shown to sighted subjects, who were asked to assign labels to the pictures, in a multiple-choice format. The labels were assigned at a rate above chance. We argue that the pictures are metaphoric and that pictorial metaphor relies on common properties of the static picture and the kinetic referent. PMID- 11206213 TI - Immunity to functional fixedness in young children. AB - In the candle problem (Duncker, 1945), subjects must attach a candle to a vertical surface, using only a box of tacks and a book of matches. Subjects exhibit functional fixedness by failing, or being slow, to make use of one object (the tack box) as a support, rather than as a container, in their solutions. This failure to produce alternate functions is measured against improved performance when the tack box is presented empty rather than full of tacks (i.e., not preutilized as a container). Using an analogous task, we show that functional fixedness can be demonstrated in older children (6- and 7-year-olds); they are significantly slower to use a box as a support when its containment function has been demonstrated than when it has not. However, younger children (5-year-olds) are immune to this effect, showing no advantage when the standard function is not demonstrated. Moreover, their performance under conditions of preutilization is better than that of both older groups. These results are interpreted in terms of children's developing intuitions about function and the effects of past experience on problem solving. PMID- 11206214 TI - Modeling the effects of repetition and word frequency in perceptual identification. AB - The counter model for word identification (Ratcliff & McKoon, 1997) has been challenged by recent empirical findings that performance on low-frequency words improves as the result of repetition of the words. We show that the model can accommodate this learning effect, and that it can do so without jeopardizing its explanations of the effects on word identification of a large number of other variables. PMID- 11206215 TI - A criterion-shift model for enhanced discriminability in perceptual identification: a note on the counter model. AB - The original version of the counter model for perceptual identification (Ratcliff & McKoon, 1997) assumed that word frequency and prior study act solely to bias the identification process (i.e., subjects have a tendency to prefer high frequency and studied low-frequency words, irrespective of the presented word). In a recent study, using a two-alternative forced-choice paradigm, we showed an enhanced discriminability effect for high-frequency and studied low-frequency words (Wagenmakers, Zeelenberg, & Raaijmakers, 2000). These results have led to a fundamental modification of the counter model: Prior study and high frequency not only result in bias, but presumably also result in a higher rate of feature extraction (i.e., better perception). We demonstrate that a criterion-shift model, assuming limited perceptual information extracted from the flash as well as a reduced distance to an identification threshold for high-frequency and studied low-frequency words, can also account for enhanced discriminability. PMID- 11206216 TI - Working memory and interference: a comment on Jenkins, Myerson, Hale, and Fry (1999). AB - Jenkins, Myerson, Hale, and Fry (1999) showed that slopes relating complex spans to simple spans were considerably smaller than one, indicating that persons with higher simple spans suffered more interference when the span task was combined with a processing demand. They argued that this finding ruled out accounts of working memory based on interference and/or inhibition of interfering information. We demonstrate that the effect is mainly an artifact from regression to the mean, owing to the low reliability of span scores as used by Jenkins et al. Data from 133 young adults for two verbal and two spatial span tasks show that the slopes relating complex to simple performance are considerably higher for sum scores than for span scores. Furthermore, an adequate test for an interference or an inhibition account of working memory is to predict interference from complex span tasks, not from simple span tasks. Interference effects in the verbal span tasks were negatively correlated with an independent measure of working memory capacity, consistent with the interference/inhibition account. PMID- 11206217 TI - The training of surgeons in America. PMID- 11206218 TI - Complementarity of blue dye and isotope in sentinel node localization for breast cancer: univariate and multivariate analysis of 966 procedures. AB - BACKGROUND: The hypothesis that sentinel lymph node (SLN) mapping in breast cancer patients is optimized by combining blue dye and isotope is reasonable and intuitive. Despite this, few studies examine in detail the factors contributing to the success of these techniques, either individually or in combination. METHODS: During a time period of 21/2 years, 1000 consecutive patients at Memorial Sloan-Kettering Cancer Center had SLN mapping performed by using both blue dye and isotope, with preoperative lymphoscintigraphy (LSG). Among the 966 patients with invasive cancer, 12 variables were examined for their correlation with the success of SLN localization by blue dye, by isotope, and by the combined method, using univariate and multivariate models. RESULTS: By univariate analysis, blue dye success was more frequent in association with: a positive LSG (P = .02), age < or = 60 (P < .0005), a previous surgical biopsy (P = .03), and an outer quadrant tumor (P < .0005). Isotope success was more frequent with a positive LSG (P < .0005), age < or = 60 (P = .004), and intradermal isotope injection (P < .0005). Combined (dye and/or isotope) success was more frequent when there was a positive LSG (P < .0005), age < or = 60 (P = .006) and intradermal isotope injection (P < .0005). In multivariate analysis, blue dye success remained uniquely associated with outer quadrant tumor location (P < .0005), and isotope success was uniquely associated with intradermal isotope injection (P = .012). Combined success was more frequent with a positive LSG (P < .0005), age < or = 60 (P = .033), and intradermal isotope injection (P = .003). CONCLUSIONS: The five variables associated with successful SLN localization by blue dye or by isotope overlap but are not identical. Only three of these, intradermal isotope injection, a positive LSG, and age < 60, predicted success by the dye-isotope combination in the multivariate model. Dye and isotope complement each other, and SLN biopsy for breast cancer should use both. PMID- 11206219 TI - Intradermal isotope injection: a highly accurate method of lymphatic mapping in breast carcinoma. AB - BACKGROUND: The combined approach of radioactive tracer and blue-dye mapping of sentinel lymph nodes (SLN) has evolved into a safe and effective alternative to routine axillary node dissection in specific patient populations with breast carcinoma. The optimal route of injection for the isotope has not been clearly defined. To assess the intradermal route of isotope injection, we prospectively evaluated 100 patients with biopsy-proven invasive breast carcinoma with SLN biopsy followed by planned axillary node dissection. METHODS: All patients were given an intradermal injection of Tc-99m sulfur colloid and an intraparenchymal injection of blue dye. All patients underwent a complete axillary node dissection. Each sentinel node was serially sectioned and examined by immunohistochemistry. RESULTS: Sentinel nodes were successfully identified in 99% of cases. Forty-six patients had axillary metastases; of these, four had falsely negative sentinel nodes (false-negative rate, 9%). The false-negative rate was 0 of 24 (0%) for T1 tumors, 2 of 18 (11%) for T2 tumors, and 2 of 4 (50%) for T3 tumors. Three of four patients with false negatives had palpable, clinically suspicious axillary nodes found intraoperatively. If these cases are excluded, the accuracy of the procedure was 100% for T1 and T2 tumors. Of the 42 positive axillae identified by SLNB (true positives), 40 were localized using the intradermal injection of radioisotope; in 13 of these cases, this was the only method that identified the true-positive node. CONCLUSION: These data demonstrate that intradermal injection of radioactive tracer is an effective method of localizing the SLN in cases involving small breast cancers. Further investigation is warranted before this technique is adopted for use in larger breast cancers. Intraoperative examination and biopsy of any suspicious nonsentinel nodes are critical. PMID- 11206220 TI - Effect of breast surgery on serum levels of insulin-like growth factors (IGF-I, IGF-II, and IGF binding protein-3) in women with benign and malignant breast lesions. AB - BACKGROUND: There is evidence that insulin-like growth factors play a role in the development of breast cancer. Antiestrogens reduce circulating levels of IGF-I, but the influence of other breast cancer treatments, including surgery, is unknown and is investigated in this study. METHODS: Circulating serum concentrations of IGF-I, IGF-II, and IGF binding protein-3 (IGFBP-3) were measured before and after breast surgery in 31 patients with breast cancer and 12 controls with benign breast lesions. Serum albumin was measured as a marker of the nonspecific metabolic effect of surgery. RESULTS: Serum IGF-I, IGF-II, IGFBP 3, and albumin fell 24 hours after surgery for breast cancer but largely normalized again over the next 7 days. The fall in IGF-I and IGFBP-3 was not significant when the change in serum albumin was used as a covariate, suggesting a nonspecific effect of surgery. However, the reduction in IGF-II remained significant when adjusted for albumin and was greater after lumpectomy of malignant tumors (-8 +/- 2%) compared with benign disease (2 +/- 2%, P = .001). The fall in IGF-II was significantly related to the size of the removed tumor. CONCLUSIONS: Breast cancer may directly influence the serum concentration of IGF II, possibly by direct tumor production. PMID- 11206221 TI - Modification of the sentinel node technique: it was a hit in New York, but will it play in Poughkeepsie? PMID- 11206222 TI - Antisense TGF-beta2 immunotherapy for hepatocellular carcinoma: treatment in a rat tumor model. AB - BACKGROUND: The overexpression of transforming growth factor-beta (TGF-beta) in hepatocellular carcinoma (HCC) appears to induce immunosuppression toward the tumor cells. METHODS: A rat HCC cell line, Morris hepatoma rat cell line (MRH) 7777 (MRH), was transfected with antisense TGF-beta2 in pCEP-4 vector and used as immunotherapy against the development of wild-type tumors. An enzyme-linked immunosorbent assay (ELISA) confirmed that TGF-beta2 production was markedly lower for antisense modified cells as compared to wild-type tumor cells. Tumors were initiated by injecting MRH cells into the flanks of Buffalo rats. This was followed by biweekly vaccinations with irradiated MRH cells (unmodified, pCEP-4 alone, or antisense TGF-beta2 modified). RESULTS: In the group that received irradiated MRH unmodified cells, 55% of rats died from tumor burden, and 36% developed tumor regression. In the group that received irradiated MRH cells modified with pCEP-4 vector alone, 50% died from tumors and 33% had spontaneous regression. In animals treated with pCEP-4/TGF-beta antisense modified cells, none developed tumors. Cell-mediated cytotoxicity assays demonstrated a twofold increase in lytic activity in the effector cells of the animals treated with antisense modified cells. CONCLUSIONS: These results demonstrate the successful treatment of HCC tumors in rats by a HCC vaccine genetically altered with antisense TGF-beta2. Decreased production of TGF-beta in HCC vaccine enhances immunogenicity against wild-type HCC tumor cells. PMID- 11206223 TI - Role for surgical cytoreduction in multimodality treatments for cancer. PMID- 11206224 TI - The effect of treatment for colorectal cancer on long-term health-related quality of life. AB - BACKGROUND: Little information is available on the impact that therapies used in the treatment of colorectal cancer (CRC) have on long-term, health-related quality of life (HRQL). Knowledge of how HRQL is affected by these therapies is essential in properly selecting patients for treatment. The purpose of this study was to determine the long-term impact that surgical and adjuvant therapy for resectable CRC has on patient-reported HRQL in a male veteran population through a case-control design. METHODS: All participating patients had completed therapy at least 6 months before enrollment. One hundred fifty-eight patients were accrued over a 3-year period (January 1, 1997 to December 31, 1999) at a single institution. The impact of CRC surgery on HRQL was measured by comparing a cohort of 61 patients undergoing surgery alone for the treatment of CRC (CRC-S group) with 44 patients undergoing surgery for benign colonic disease (BCD group). To study the effect of adjuvant therapy for CRC on HRQL, a third cohort of 53 patients undergoing both surgical and adjuvant treatment (CRC-S/A group) was compared with the CRC-S group. For each group, health status was measured by a health survey questionnaire, SHORT FORM 36 (SF36). For patients treated for CRC, an additional disease-specific supplemental questionnaire also was used. RESULTS: Self-reported health status, as measured by mean SF36 score, was significantly reduced for the BCD group compared with CRC-S patients on general health perception (41.9 +/- 3.9 vs. 52.2 +/- 3.0, P = .04) and the standardized physical component score (31.2 +/- 1.7 vs. 37.5 +/- 1.5, P < .005). Despite an increased number of distally located tumors, later stage cancers, and an increased number of recurrences in the CRC-S/A group compared with the CRC-S cohort, no significant differences were identified between these groups on any of the subscales or standardized scores of SF36. Using the supplemental questions, no differences were identified between the CRC groups with respect to appetite, weight, or gastrointestinal or urinary functioning. CONCLUSIONS: Surgical therapy for CRC probably has minimal impact on long-term HRQL when compared with surgery for benign colonic processes. Similarly, there does not appear to be a measurable, lasting impact of CRC adjuvant therapy on HRQL when compared with surgery alone. Although overall impact of therapies for CRC on HRQL appears to be limited, measurement of therapeutic influence on an individual level and identification of selection criteria based on estimated impact on HRQL for these therapies requires prospective validation. PMID- 11206225 TI - Malignant gastrointestinal stromal tumors of the small intestine: a review of 50 cases from a prospective database. AB - BACKGROUND: Malignant gastrointestinal stromal tumors (M-GIST) are rare mesenchymal tumors originating in the wall of the gastrointestinal (GI) tract. Previous studies have included limited numbers of patients, and most included malignant and benign cases from throughout the GI tract. We reviewed the experience of a single tertiary cancer care center with M-GIST of the small intestine only. METHODS: A prospective database identified all patients seen from 1989 to 1998. Clinical and pathological data, treatment, and outcome were analyzed. Overall median follow-up time was 24 months (range, 1-176 months). RESULTS: Fifty patients (31 male, 19 female) were identified. Mean age at diagnosis was 55 years. Disease was localized in 11 patients, locally advanced (invasion into adjacent organs/peritoneum) in 24 patients, perforated in 4 patients, multiple primary lesions in 2 patients, and distant metastases in 9 patients. All patients underwent resection, which was complete in 70%. Locoregional recurrence (LR) developed in 43% (median, 25 months), and distant metastases in 59% (median, 21 months) of patients at risk. At last follow-up, 14 patients were alive (6 disease-free), 2 had died disease-free, and 34 died with recurrent disease. Overall survival (OS) was similar for localized and locally advanced disease; OS also was similar for patients with multiple primaries and distant metastases at diagnosis. Patients were grouped into three stages: (I) patients with localized and locally advanced disease; (II) patients with perforated; and (III) patients with multiple primaries and distant metastases. Actuarial OS at 5 years was 41% (n = 50)--42% for those with complete resection and 8% for incomplete resection. Univariable analysis showed that earlier stage at diagnosis (P = .001) and completeness of resection (P = .004) predicted for longer OS. CONCLUSIONS: Most patients with M-GIST of the small intestine relapse following resection, but survival may be prolonged. In univariable analysis, stage at presentation and complete resection were significant prognostic variables for OS; grade was not significant. Localized and locally advanced M GIST of the small intestine have a mean OS > 5 years. Complete resection should be the goal of initial surgical treatment. PMID- 11206226 TI - Treatment of malignancy arising in pilonidal disease. AB - BACKGROUND: Malignant degeneration is a rare complication of pilonidal disease and is associated with a high recurrence rate and poor prognosis compared with regular nonmelanoma skin cancer. Treatment in our departments and in the international literature was evaluated. METHODS: We analyzed the data from three patients with malignant degeneration who were treated in our departments and an additional 56 patients who were found after an extensive literature search. RESULTS: A total of 47 males and 12 females, with a mean age of 52 years, were most frequently primarily treated with surgery. After a mean follow-up time of 28 months, 20% of all patients died with evidence of disease and an additional 10% died of unrelated causes. The overall recurrence rate was 39%, with a median time to recurrence of only 9 months. The local recurrence rate was lower when radiotherapy was added to surgical treatment alone (30% vs. 44%). Re-excision of local recurrence resulted in some long-term survivals. CONCLUSIONS: Early diagnosis and treatment may lead to improvement of the relative poor prognosis. Surgical treatment should be tailored according to the locoregional extent. The high recurrence rate after surgical treatment can be reduced by the addition of radiotherapy. Although repeat surgery for recurrent disease may involve extensive resection and morbidity, this may result in prolonged survival. PMID- 11206227 TI - Phase II trial of debulking surgery and photodynamic therapy for disseminated intraperitoneal tumors. AB - BACKGROUND: Photodynamic therapy (PDT) combines photosensitizer drug, oxygen, and laser light to kill tumor cells on surfaces. This is the initial report of our phase II trial, designed to evaluate the effectiveness of surgical debulking and PDT in carcinomatosis and sarcomatosis. METHODS: Fifty-six patients were enrolled between April 1997 and January 2000. Patients were given Photofrin (2.5 mg/kg) intravenously 2 days before tumor-debulking surgery. Laser light was delivered to all peritoneal surfaces. Patients were followed with CT scans and laparoscopy to evaluate responses to treatment. RESULTS: Forty-two patients were adequately debulked at surgery; these comprise the treatment group. There were 14 GI malignancies, 12 ovarian cancers and 15 sarcomas. Actuarial median survival was 21 months. Median time to recurrence was 3 months (range, 1-21 months). The most common serious toxicities were anemia (38%), liver function test (LFT) abnormalities (26%), and gastrointestinal toxicities (19%), and one patient died. CONCLUSIONS: Photofrin PDT for carcinomatosis has been successfully administered to 42 patients, with acceptable toxicity. The median survival of 21 months exceeds our expectations; however, the relative contribution of surgical resection versus PDT is unknown. Deficiencies in photosensitizer delivery, tissue oxygenation, or laser light distribution leading to recurrences may be addressed through the future use of new photosensitizers. PMID- 11206228 TI - Localizing the sentinel node outside of the specialty center: success of a lymphatic mapping course in disseminating new technology. AB - BACKGROUND: Sentinel node biopsy (SNB) is an evolving technology in the management of breast cancer. The purpose of this study was to determine the success of an SNB course in emphasizing principles for participants to successfully initiate an SNB program at their institution. METHODS: Participants in a university-sponsored course were queried 6 to 18 months after the course regarding their success in initiating SNB in their practice. Univariate analysis was used to determine the likelihood of implementing a SNB program. RESULTS: Ninety-one participants responded. Of these respondents, 56 had initiated an SNB program at their hospital, and 20 had completed a "validation" phase. "Validation" consisted of less than 10 cases for 11 respondents, 11 to 20 cases for 5 respondents, and 20 to 30 cases for 3 respondents and >30 cases for 1 respondent. Twenty-eight percent initiated the learning curve without an Institutional Review Board (IRB) protocol, and a further 20% went on to utilize SNB without axillary dissection in sentinel node-negative patients without IRB approval. Univariate analysis revealed that surgeons practicing in a group whose caseload consisted of more than 25% breast surgery cases were most likely (P < 0.05) to implement SNB in their practice. CONCLUSIONS: Success in applying SNB after a course is high among surgeons in groups with a significant breast caseload, although recommendations for obtaining institutional approval and completing a 30-case validation series are often disregarded. PMID- 11206229 TI - Vascular endothelial growth factor expression in stage I non-small cell lung cancer correlates with neoangiogenesis and a poor prognosis. AB - BACKGROUND: Vascular endothelial growth factor (VEGF) plays an important role in tumor growth and metastasis. We investigated the prognostic significance of VEGF overexpression, intratumoral microvessel density (MVD), and angiolymphatic invasion in stage Ia-b non-small cell lung cancer (NSCLC). METHODS: Eighty-five patients undergoing complete surgical resection of pathologic stage Ia-b NSCLC were evaluated. The mean and median clinical follow-up were 37.1 and 39.0 months (range, 30-44 months), respectively. Paraffin-embedded tumor specimens were stained with VEGF and CD31 (a specific endothelial marker) using immunohistochemical methods. VEGF staining was evaluated, by combining both percentage of positive tumor cells and staining intensity, as low (negative and < 20% of tumor cells showing weak positivity), or high (> 20% of tumor cells showing strong positivity). CD31 staining was expressed as MVD per high power field at 400x magnification. Angiolymphatic invasion was expressed as either presence or absence. RESULTS: Low VEGF expression was seen in 25 (29%) patients, and high VEGF expression was seen in 60 (71%) patients. The survival rate in patients with low VEGF expression was significantly higher (80%) than that in those with high VEGF expression (48%, P = .018). The mean MVD in the low VEGF group was 23.7 +/- 5.7 vs. 34.4 +/- 9.3 in the high VEGF group (P = .001). Patients with high MVD also had a significantly lower survival rate than did those with low MVD count (46% vs. 73%, P = .0053). Age, sex, tumor type, and tumor differentiation were not found to be associated with overall survival. The presence of angiolymphatic invasion and T2 stage (i.e., tumor size > 3 cm) were associated with decreased survival. High VEGF expression, tumor size, and angiolymphatic invasion emerged as three independent factors predicting worsening prognosis using multivariate analysis. CONCLUSION: High VEGF expression within stage I NSCLC is closely associated with high intratumoral angiogenesis and poor prognosis. Immunohistochemical evaluation of T stage and VEGF expression along with examination of angiolymphatic invasion perioperatively may aid in predicting prognosis. Adjuvant therapies aimed at retarding tumor angiogenesis may be considered for stage I NSCLC patients with high VEGF levels. PMID- 11206230 TI - Accuracy of biopsy techniques for limb and limb girdle soft tissue tumors. AB - BACKGROUND: The biopsy method of choice for soft tissue sarcomas (STS) of the limb and limb girdle is controversial. There have been no randomized controlled trials that compare incision biopsy with Tru-cut biopsy. We present a large series, which includes an analysis of the effectiveness of Tru-cut core biopsy both in a tertiary referral center as well as from many referring hospitals. This is compared with the other methods of biopsy of all soft tissue tumors (STT) referred to this institution. METHODS: A retrospective review of all patients who were referred to Royal Marsden Hospital NHS Trust (RMH) from 1989 to 1998. RESULTS: There were 570 patients (576 lesions) identified. Overall Tru-cut biopsy differentiated benign from malignant tumors with a sensitivity of 99.4%, specificity 98.7%, positive predictive value 99.4%, and negative predictive value 98.7% with similar results for RMH and referral hospitals. Tru-cut identified both tumor subtype and grade in approximately 80% of STS. Incision biopsy had similar sensitivity and specificity for differentiating benign from malignant STT as well as subtype of STS but was less accurate for grade assessment. Tumors from patients who were referred after enucleation had a median maximum tumor diameter (MTD) of 4.9 cm, whereas median MTD of tumors diagnosed at referring hospitals by Tru-cut biopsy was 10.6 cm. (P < 0.001). CONCLUSION: Tru-cut biopsy is highly sensitive and specific in the diagnosis of STT as well as subtyping and grading of STS. It is equally effective as incision biopsy in all these parameters and has a lesser morbidity. The failure to use Tru-cut biopsy is most likely because of the possibility that STS is not suspected in patients with small tumors even when they are deep to the investing fascia. PMID- 11206231 TI - Rib pain in a 23-year-old woman with severe asthma. AB - This case illustrates the importance of considering a wide range of diagnoses in patients complaining of rib, flank, and pleuritic pain. Further, additional evaluation is warranted when "pneumonia" does not respond to conventional treatment. PMID- 11206232 TI - A randomized, 12-week, double-blind, placebo-controlled study comparing formoterol dry powder inhaler with albuterol metered-dose inhaler. AB - BACKGROUND: Formoterol is a beta2-adrenergic agent which, when inhaled, produces rapid and long-lasting bronchodilatation. OBJECTIVE: The aim of this study was to compare the efficacy, safety, and tolerability of formoterol powder for inhalation delivered via the Aerolizer device with placebo and with albuterol delivered via metered-dose inhaler in patients with mild to moderate persistent asthma. METHODS: In a multicenter, double-blind, parallel-group study, 541 patients were randomized at 26 trial sites to receive either formoterol, 12 microg twice daily; formoterol, 24 microg twice daily; albuterol, 180 microg four times daily; or a placebo for 12 weeks. The effects of each treatment on lung function, asthma symptoms, and frequency of rescue albuterol use were evaluated. Adverse effects and clinical laboratory parameters were also evaluated. RESULTS: The bronchodilatory effects of formoterol were rapid in onset and persisted for 12 hours. Both formoterol doses were more effective than placebo and albuterol for objective measures of lung function. Morning and evening peak expiratory flow rates were more improved with formoterol, and formoterol provided significantly greater improvements in asthma symptom scores compared with both albuterol and placebo. Overall, patients taking formoterol used significantly less rescue medication than did those taking albuterol or placebo. Nocturnal awakenings occurred less often with formoterol than with placebo or albuterol. The therapeutic effects of formoterol were maintained over the entire 12 weeks of treatment. Adverse events were similar for all treatment groups, and clinical laboratory data were unremarkable. CONCLUSIONS: Rapid-onset, long-acting formoterol, administered via the Aerolizer inhaler, is an effective and safe treatment for patients with mild to moderate persistent asthma. PMID- 11206233 TI - Lane markers and guardrails. PMID- 11206234 TI - Efficacy of azelastine nasal spray in the treatment of vasomotor (perennial nonallergic) rhinitis. AB - BACKGROUND: Azelastine hydrochloride is an antihistamine with anti-inflammatory properties that is available in the United States in a nasal spray formulation for the treatment of seasonal allergic rhinitis. Vasomotor (perennial nonallergic) rhinitis (VMR) is a noninfectious, chronic rhinitis usually not associated with inflammatory cell infiltration. OBJECTIVE: Two multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trials were conducted to determine whether patients with symptoms of VMR (rhinorrhea, sneezing, postnasal drip, and nasal congestion) could be effectively treated with azelastine nasal spray. METHODS: All of the patients who participated in the trials had a diagnosis of VMR, symptoms for at least 1 year, negative skin tests for a mixed panel of seasonal and perennial allergens, and a nasal cytology examination negative for eosinophils. After a 1-week, single-blind, placebo lead in period, patients who met the symptom severity qualification criteria were randomized to receive either azelastine nasal spray (two sprays per nostril twice daily, 1.1 mg/day) or placebo nasal spray for 21 days. Patients recorded the severity of their VMR symptoms on diary cards each morning and evening of the trial using a four-point symptom rating scale (0 = none to 3 = severe). The primary efficacy variable was the overall reduction from baseline in the total vasomotor rhinitis symptom score (TVRSS) over the 21-day, double-blind treatment period. RESULTS: In both studies, azelastine nasal spray significantly (study 1, P = .002; study 2, P = .005) reduced the TVRSS from baseline when compared with placebo. Significant improvement was observed within the first week and improvement in all symptoms favored treatment with azelastine nasal spray. No serious or unexpected adverse events were reported in either study. Bitter taste (19% vs 2%) was the only adverse experience that occurred with a statistically significantly greater incidence in the azelastine group than in the placebo group. CONCLUSIONS: This is the first demonstration of the efficacy of an antihistamine in the therapy of VMR in two double-blind, placebo-controlled clinical trials. PMID- 11206235 TI - Long-acting bronchodilators for the control of asthma symptoms. PMID- 11206236 TI - Comparison of once-daily to twice-daily treatment with mometasone furoate dry powder inhaler. AB - BACKGROUND: Once-daily dosing with an effective inhaled corticosteroid (ICS) would likely enhance compliance and, therefore, aid in the management of asthma. OBJECTIVE: Several once-daily dosing regimens of mometasone furoate (MF) administered by dry powder inhaler (DPI) were compared with a twice-daily dosing regimen in 286 patients with mild to moderate persistent asthma who were previously being treated with ICS. METHODS: During a 2-week open-label phase, patients received MF-DPI, 200 microg twice daily. They were then randomized to continue MF-DPI, 200 microg twice-daily treatment or to receive MF-DPI, 200 microg once daily in the morning (AM), 200 microg once daily in the evening (PM), 400 microg once daily AM, or placebo as part of the 12-week, double-blind phase. The primary efficacy variable was the mean change from the baseline to endpoint (last evaluable observation) for FEV1. RESULTS: Once-daily MF-DPI, 400 microg, AM maintained FEV1, and morning peak expiratory flow rate, FVC, FEF25%-75%, and asthma symptom scores, at levels similar to those for MF-DPI, 200 microg twice daily and significantly better than placebo. Once-daily MF-DPI, 200 microg, PM was effective in maintaining pulmonary function, but was less effective on other efficacy measures. In comparison to the other MF-DPI groups, once-daily MF-DPI, 200 microg, AM was not as effective overall. The incidence of local adverse events, including oral candidiasis, was low with all dosages. CONCLUSIONS: Once daily MF-DPI, 400 microg, AM was as effective as MF-DPI, 200 microg twice daily, whereas once-daily MF-DPI, 200 microg, was more effective when administered in the evening compared with morning, for patients receiving ICS therapy. Once-daily dosing offers an effective and convenient treatment that could aid compliance in the treatment of asthma. PMID- 11206237 TI - Suppression of the early and late cutaneous allergic responses using fexofenadine and montelukast. AB - BACKGROUND: The relative contribution of histamine and the cysteinyl leukotrienes to the early and late cutaneous allergic responses (ECAR and LCAR) can be studied using antagonists of these mediators. OBJECTIVE: To determine the relative suppression of the ECARs and LCARs using standard doses of an H1-receptor antagonist, a cysteinyl leukotriene1-receptor antagonist, and the two antagonists administered concurrently. METHODS: We carried out a prospective, randomized, double-blind, placebo-controlled, four-way crossover study in 12 highly allergic participants. Intradermal tests with standardized allergen, and with histamine phosphate, LTD4, and saline controls were performed on 5 different test days as follows: pretreatment baseline and at steady state immediately after the seventh and last dose of a 1-week course of treatment with once-daily fexofenadine, 120 mg; montelukast, 10 mg; fexofenadine and montelukast administered concurrently; or placebo. On each test day, the skin test results were read at intervals from 0.25 to 24 hours after the intradermal injections were performed. RESULTS: After allergen injection, compared with baseline, all treatment regimens significantly decreased the ECAR and LCAR. After allergen injection, compared with placebo, fexofenadine significantly decreased the ECAR and the LCAR from 0.25 to 2 hours and at 8 hours. Montelukast did not significantly decrease the ECAR or LCAR. Fexofenadine and montelukast administered concurrently were not more effective than fexofenadine alone at any time. In the control skin tests, compared with placebo, fexofenadine, but not montelukast, significantly decreased the histamine induced response, and montelukast, but not fexofenadine, significantly decreased the LTD4-induced response. CONCLUSIONS: Fexofenadine and montelukast administered concurrently were not significantly more effective than fexofenadine alone in decreasing the ECAR and LCAR. Montelukast does not need to be discontinued before allergen skin testing. Further studies of the effect of concurrent treatment with higher doses of a histamine antagonist and a leukotriene modifier on the allergic response in the skin are needed. PMID- 11206238 TI - Practice parameters: background and usefulness. AB - BACKGROUND/OBJECTIVE: The number of clinical practice parameters has been increasing in recent years. A more complete understanding of the development of parameters will help the clinician understand the purpose of practice parameters and how to use them in their clinical practice. DATA SOURCE: The MEDLINE database was used to review the recent English language literature about practice parameters. CONCLUSIONS: The overall goal of practice parameters is to improve patient care. Practice parameters may be considered a major tool that can aid the clinician in decision-making, and improve overall health care for patients. They can help reduce unwanted variation in clinical practice and help physicians make more efficient use of resources. Practice parameters can also be used as teaching tools, reference documents, and aids to help defend patient care decisions, particularly in managed health care situations. PMID- 11206239 TI - Cockroach allergy appears early in life in inner-city children with recurrent wheezing. AB - BACKGROUND: Cockroach allergy and exposure to high levels of this allergen are important in the increasing asthma-related health problems among young inner-city children. However, there are very little data regarding the prevalence of cockroach allergy in infants and young children with asthma. OBJECTIVE: This retrospective study was designed to test the hypothesis that cockroach allergy appears early in life in young children with recurrent wheezing. METHODS: We reviewed the medical records of all 196 children (ages 5 months to 16 years) evaluated between January 1995 and September 1997 at the Cook County Hospital Pediatric Allergy Clinic for recurrent wheezing. The patients were assigned into two age groups, less than 4 years old and 4 to 16 years old. The percentages of IgE skin tests positive for common aeroallergens were compared within and between the two age groups. All children in the younger age group were tested for cockroach and dust mites, cat, and dog when indicated by positive environmental history. All children in the older age group were tested for indoor and outdoor allergens. RESULTS: Sixty-three children were younger than 4 years of age, and of these, 15 (23.8%) had cockroach allergen sensitivity, compared with only eight patients (12.7%) who were skin test positive to dust mite allergen (P = .01). The youngest patient with a positive reaction to cockroach allergen was 6 months old. Patients with a single allergen skin reactivity were considered as monosensitized. Nine children younger than 4 years of age (14.3%) were monosensitized only to cockroach allergen in contrast to three children (4.8%) who were monosensitized to house-dust mites (P < .05). CONCLUSIONS: Our data suggest that cockroach allergen sensitivity starts early in life and may be the only sensitizing allergen in many young inner-city children. PMID- 11206240 TI - Immunoglobulin deficiency in children with a sudden overwhelming infection. AB - BACKGROUND: A small percentage of previously healthy children develop a sudden overwhelming infection (SOI) that rapidly progresses and results in shock and, occasionally, death. Some of these children may have an undetected Ig deficiency. OBJECTIVE: The aim of this study was to evaluate the incidence of Ig deficiency in children with a SOI. METHODS: A case series study was conducted in a university hospital and included 18 children who either died in the emergency room or required admission to the pediatric intensive care unit secondary to a SOI. Two age-matched control groups included children hospitalized to regular floor beds with an infectious process (infected control group) or a noninfectious process (noninfected control group). Serum left from the initial blood draw, before fluid resuscitation, was collected and stored at -70 degrees C. Total IgG, IgG subclasses, IgM, and IgA were assayed by rate nephelometry in a blinded fashion. RESULTS: In the study group, one of six children under 1 year of age had low Ig levels in comparison with two of nine control patients. In those children over the age of 1 year, 8 of 12 patients (67%) had low Ig levels as compared with 2 of 19 controls (11%) by Fisher's exact test, P = .002. Of those patients with Ig deficiencies, three of eight had isolated IgG deficiency, two of eight had combined IgG and IgA deficiency, three of eight had combined IgG and IgM deficiency. CONCLUSIONS: Children over the age of 1 year who present with a SOI have a significantly higher incidence of Ig deficiencies compared with age matched controls. PMID- 11206241 TI - Tobacco hypersensitivity and environmental tobacco smoke exposure in a pediatric population. AB - BACKGROUND: Skin testing and RAST have verified the existence of tobacco-specific IgE. However, published studies report conflicting results concerning the clinical significance of tobacco IgE. Previous studies have not focused on the role of environmental tobacco smoke (ETS) as it relates to tobacco hypersensitivity (TH) in nonsmoking children. OBJECTIVE: We used nonsmoking pediatric patients to investigate the relationship between ETS and TH. METHODS: Children, ages 4 to 10 years, were prospectively enrolled. ETS exposure and smoke triggered symptoms were recorded by questionnaire and physician history. Patients were given a skin test (ST) with a panel of aeroallergens plus tobacco extract. A ST reaction to at least one aeroallergen classified a patient as atopic; a ST reaction to tobacco classified a patient as TH. RESULTS: We enrolled 170 patients, mean age 7.2 years. We found 58 (34%) patients reported routine exposure to ETS and 78 (46%) patients reported ETS-induced symptoms. We found 121 (71%) atopic patients and 61 (36%) TH patients. TH was more common in atopic patients (P < .0001) and those routinely exposed to ETS (P < .05). However, TH failed to predict ETS-induced symptoms in either atopic or non-atopic patients (PPV = 0.40, NPV = 0.69). CONCLUSIONS: We evaluated the clinical significance of TH in a nonsmoking patient population related to ETS exposure. We concluded that although TH is statistically related to atopy and ETS exposure, the low predictive values of skin testing for TH limit its clinical usefulness. PMID- 11206242 TI - Repeated exposure to low levels of sulfur dioxide (SO2) enhances the development of ovalbumin-induced asthmatic reactions in guinea pigs. AB - BACKGROUND: Sulfur dioxide (SO2) is one of the major air pollutants. It is known to aggravate asthma symptoms in human beings, but few studies have focused on the effects of SO2 upon the development of bronchial asthma in animal models. OBJECTIVE: This study was undertaken to evaluate the role of SO2 upon the development of ovalbumin (OA)-induced asthmatic reactions in guinea pigs. METHODS: Guinea pigs were divided into four groups: (1) OA- and SO2-exposed group (n = 12), (2) SO2-exposed group (n = 12), (3) OA-exposed group (n = 11), and (4) saline-exposed group (n = 7). Guinea pigs of the first and second groups were exposed to 0.1 ppm SO2 for 5 hours a day on 5 consecutive days. Guinea pigs in the first and third groups inhaled 0.1% OA aerosols for 45 minutes a day on days 3, 4, and 5. One week after the sensitization procedure, all the guinea pigs underwent bronchial challenge with 1.0% OA aerosols, using unrestricted whole body plethysmography. Bronchoalveolar lavage and histopathologic examination were performed 24 hours after the bronchial challenge. RESULTS: Increases in enhanced pause (Penh), as an index of airway obstruction, after the bronchial challenge was significantly higher in OA- and SO2-exposed group (group 1) than the other groups (P < .05, respectively). Eosinophil counts in bronchoalveolar lavage fluids were also significantly higher in group 1 than in the other groups (P < .05, respectively). Histopathologic findings of bronchial and lung tissue in the group 1 showed an infiltration of inflammatory cells, bronchiolar epithelial damage, and mucus and cell plug in the lumen, but no significant abnormalities were observed in the other groups. CONCLUSIONS: These results indicate that repeated exposure to low levels of sulfur dioxide may enhance the development of ovalbumin-induced asthmatic reactions in guinea pigs. PMID- 11206244 TI - Mountain cedar. PMID- 11206243 TI - Anaphylaxis to raw potato. AB - BACKGROUND: Potato allergy has been described rarely, generally in relation to the Oral Allergy Syndrome (OAS). Adults with seasonal allergic rhinitis have been reported in whom peeling of raw potatoes causes oculonasal symptoms, wheezing, and contact urticaria. Skin testing with fresh fruits and vegetables has been recommended in cases of OAS, although the sensitivity of commercial potato extract is reportedly equal to that of fresh potato. CASE REPORT: This report describes a 4-year-old with raw potato-induced anaphylaxis. He rapidly developed urticaria, angioedema, respiratory distress, vomiting and diarrhea after biting into a raw potato that was being used for painting in preschool. Review of systems is significant for viral-induced wheezing, but no symptoms suggestive of seasonal allergic rhinitis were evident. His mother has a history of seasonal allergic rhinitis and contact urticaria with raw potato. Skin testing to commercial potato extract was negative and skin testing to fresh potato by the prick + prick method was markedly positive. Skin testing to birch tree was negative. An open challenge to a small amount of cooked potato was negative. Food challenge to raw potato was not considered indicated in this case of immediate anaphylaxis to a single food. CONCLUSIONS: This patient had clinical and skin test reactivity to raw and uncooked potato in the absence of OAS. The patient will be followed for the development of seasonal allergic rhinitis. PMID- 11206245 TI - American Dental Education Association 78th Annual Session. Chicago, Illinois, USA. March 3-7, 2001. Abstracts. PMID- 11206246 TI - Honesty--a fundamental trait. PMID- 11206247 TI - Low-risk stress fractures. AB - Stress fractures can occur in almost any bone in the body, with the lower extremity weightbearing bones, especially the tibia, tarsals, and metatarsals, being affected most frequently. Although the cause of these fractures is multifactoral, repetitive physical forces without adequate rest are the primary culprits. Stress fractures may be broadly classified as low-risk or high-risk injuries. Low-risk stress fractures, the topic of this review article, can be diagnosed through a thorough history, physical examination, and radiographs. Nuclear scintigraphy is occasionally necessary for confirmation, especially for fractures of the spine and pelvis. When diagnosed early and treated with restriction of activity, low-risk stress fractures have a favorable prognosis. PMID- 11206248 TI - Osteochondritis dissecans of the patellofemoral joint. PMID- 11206249 TI - Nonoperative treatment of ulnar collateral ligament injuries in throwing athletes. AB - Ulnar collateral ligament injury of the elbow in throwing athletes is a common occurrence, and either operative or nonoperative treatment is an option. The results of operative repairs and reconstructions have been well documented in the literature; however, little information has been reported on the outcome of nonoperative treatment. From 1994 to 1997, we evaluated 31 throwing athletes with ulnar collateral ligament injuries. The purpose of this study was to determine what percentage of athletes could return to their sport without surgical intervention and to identify factors that would predict return to full competition by an athlete treated nonoperatively. The factors studied included acute versus insidious onset of symptoms, the duration of symptoms before treatment, and age. Nonoperative treatment, which included a minimum of 3 months' rest with rehabilitation exercises, allowed 42% of the athletes in our study (N = 13) to return to their previous level of competition. Those who did return did so at an average of 24.5 weeks after diagnosis. No predictive findings obtained either through the patient's history or physical examination were found that would assist the clinician or athlete in predicting the success of nonoperative treatment. PMID- 11206250 TI - The incidence of patellofemoral osteoarthritis and associated findings 7 years after anterior cruciate ligament reconstruction with a bone-patellar tendon-bone autograft. AB - To evaluate the development of postoperative patellofemoral osteoarthritis, we performed a retrospective clinical and radiographic study of 100 patients who had undergone anterior cruciate ligament reconstruction with a bone-patellar tendon bone autograft an average of 7 years before the follow-up. Radiographic evaluation showed no patellofemoral osteoarthritis in 53 patients (group I), mild osteoarthritis in 34 patients (group II), moderate osteoarthritis in 12 patients, and severe osteoarthritis in 1 patient (group III, moderate and severe changes). The average shortening of the patellar tendon was 2.4 mm in group I, 3.9 mm in group II, and 6.8 mm in group III. The placement of the femoral or tibial tunnel of the graft, as measured from lateral radiographs, did not correlate significantly with the degree of patellofemoral osteoarthritis. Patients who developed patellofemoral osteoarthritis experienced worse final outcomes, were more often dissatisfied with the condition of the operated knee, experienced more frequent pain and swelling in the knee joint, and had poorer range of motion and poorer quadriceps muscle strength than did patients without patellofemoral osteoarthritis. Only three patients had an unstable knee, and degenerative changes in the tibiofemoral joint were uncommon. PMID- 11206251 TI - Lower-limb function among former elite male athletes. AB - To determine the relationship between previous lower-limb loading and current self-reported hip and knee disability, we sent a questionnaire to 1321 former elite male athletes who had represented Finland between 1920 and 1965 in international competitions and to 814 control subjects who had been classified as healthy at the age of 20. After adjustment for age, body mass index, and occupational group, the odds ratios of hip disability in the athletes compared with control subjects were 0.35 in endurance athletes (95% confidence interval, 0.14 to 0.85, P = 0.02), 0.56 in team sport athletes (0.28 to 1.10, P = 0.09), 0.30 in track and field athletes (0.12 to 0.73, P < 0.01), 0.84 in power sport athletes (0.51 to 1.39, P = 0.49), 0.30 in shooters (0.07 to 1.32, P = 0.11), and 0.54 (0.36 to 0.82, P < 0.01) in all athletes combined. Compared with control subjects, only team sport athletes had a higher risk of knee disability (odds ratio, 1.76; 95% confidence interval, 1.03 to 3.02; P = 0.04). Even though athletes have been reported to be at an increased risk for lower-limb osteoarthritis, our data show that former elite male endurance and track and field athletes and all athletes combined reported less hip disability than the control subjects. The effect of vigorous athletic activity on the function of knee joints is more controversial, because sports that involve a high risk of knee injury are likely to lead to pain, disability, and osteoarthritis. PMID- 11206253 TI - Prospective evaluation of syndesmotic ankle sprains without diastasis. AB - Sixty consecutive collegiate athletes with "high" ankle symptoms were prospectively evaluated over a 3-year period in an effort to better define this debilitating ankle injury. All athletes included in this study had tenderness over the distal anterior tibiofibular ligament, tenderness proximally along the interosseous membrane, and functional disability. No study subject had a fracture or frank tibia-fibula diastasis. The severity of the sprain was quantified using the interosseous "tenderness length." A standard rehabilitation protocol was followed by all patients. Athletes returned to competition when they could perform all functional testing without difficulty. Time to return to full competitive activity averaged 13.4 days. The number of days missed from competition was statistically related to the interosseous tenderness length (P = 0.0001) and to positive results on the squeeze test (P = 0.03). Fifty-three of the 60 injured athletes were evaluated at least 6 months after injury. Patients rated their outcomes as good or excellent. Six of the patients experienced occasional ankle pain and stiffness, four patients reported recurrent ankle sprains, and one patient had heterotopic ossification formation. PMID- 11206252 TI - Effect of ankle disk training combined with tactile stimulation to the leg and foot on functional instability of the ankle. AB - Twenty-two university students with unilateral functional instability of the ankle participated in this study. They were randomly assigned to one of two experimental groups. Subjects in both groups were trained to stand on the affected limb on an ankle disk. In group 1, two pieces of 1-cm wide nonelastic adhesive tape were applied to the skin around the lateral malleolus from the distal third of the lower leg to the sole of the foot before the training sessions. Subjects in group 2 participated in the training sessions without the application of the adhesive tape. Training was performed for 10 minutes a day, five times per week, for a period of 10 weeks. Subjects were tested for postural sway while standing on the affected limb before, during, and after the training period. In group 1, postural sway values decreased significantly after 4 weeks compared with the pretraining performance, and they were within the normal range after not more than 6 weeks of training. In group 2, the values did not improve significantly compared with the pretraining performance until after 6 weeks of training, and they were not within the normal range until after 8 weeks of training. The findings suggest that the 2-week earlier correction of postural sway in group 1 was due to an increased afferent input from skin receptors that were stimulated by the traction of the adhesive tape. PMID- 11206254 TI - Dynamic function after anterior cruciate ligament reconstruction with autologous patellar tendon. AB - The purpose of this study was to dynamically assess the functional outcome of patients who had undergone successful anterior cruciate ligament reconstruction using an autologous patellar tendon technique and to determine whether their dynamic knee function was related to quadriceps and hamstring muscle strength. The knee kinematics and kinetics of 22 subjects who had undergone anterior cruciate ligament reconstruction (mean age, 27 +/- 11 years) and of 22 age- and sex-matched healthy control subjects were determined during various dynamic activities using a computerized motion analysis and force plate system. The differences in the sagittal plane angles and external moments between the two groups during light (walking), moderate (climbing and descending stairs), and higher-demand (jogging, jog and cut, jog and stop) activities were related to isokinetic strength measurements. Although patients who are asymptomatic and functioning well after anterior cruciate ligament reconstruction can perform normally in light activities, higher-demand activities reveal persistent functional adaptations that require further study. PMID- 11206255 TI - Thermal chondroplasty with radiofrequency energy. An in vitro comparison of bipolar and monopolar radiofrequency devices. AB - The purpose of this study was to examine the in vitro effects of three radiofrequency energy devices (two bipolar devices and one monopolar device) for the performance of thermal chondroplasty. Thirty-two fresh bovine femoral osteochondral sections (approximately 3 x 4 x 5 cm) from eight cows were divided into four groups (three treatment patterns and one sham-operated group with eight specimens per group). The three treatment patterns consisted of 1) radiofrequency energy delivered by a mechanical jig at 1 mm/sec in a contact mode (50 g of pressure), 2) radiofrequency energy delivered by a mechanical jig at 1 mm/sec in a noncontact mode (1 mm between probe tip and articular cartilage surface), and 3) radiofrequency energy smoothing of abraded cartilage during arthroscopic visualization. Thermal smoothing of the abraded cartilage surface was accomplished with all three devices. Significant chondrocyte death, as determined by confocal laser microscopy and cell viability staining, was observed with each device. The bipolar radiofrequency systems penetrated 78% to 92% deeper than the monopolar system. The bipolar systems penetrated to the level of the subchondral bone in all osteochondral sections during arthroscopically guided paintbrush pattern treatment. Radiofrequency energy should not be used for thermal chondroplasty until further work can establish consistent methods for limiting the depth of chondrocyte death while still achieving a smooth articular for thermal chondroplasty until further work can establish consistent methods for limiting the depth of chondrocyte death while still achieving a smooth articular surface. PMID- 11206256 TI - Catastrophic injuries in pole-vaulters. AB - Pole vaulting is a unique sport in that athletes often land from heights ranging from 10 to 20 feet. We retrospectively reviewed 32 catastrophic pole-vault injuries that were reported to the National Center for Catastrophic Sports Injury Research between 1982 and 1998. The purpose of this study was to determine the mechanisms of injury so that preventive strategies can be implemented. Information was obtained by means of a telephone interview with someone familiar with the accident. All injuries occurred in male athletes at an average age of 17.5 years; 31 were catastrophic head injuries and 1 was a thoracic spine fracture that resulted in paraplegia. Three common mechanisms were identified: 17 (53%) athletes landed with their body on the landing pad and their head on the surrounding hard ground, 8 (25%) landed in the vault box after being stranded at the height of the jump, and 5 (16%) completely missed the landing pad. The mechanism of injury in the remaining two athletes was unknown. The accident resulted in death in 16 (50%) athletes and in permanent disability in 6 (19%). Increasing the minimum landing pad size and enforcing the rule requiring soft surfaces adjacent to the landing pads are the primary recommendations for preventing injuries. The authors discuss other rule and equipment changes that may help reduce the occurrence of future injuries. PMID- 11206257 TI - Fractures about the orbit in professional American football players. AB - A retrospective review was performed of records for players who suffered fractures about the orbit during participation in officially sponsored activities of the National Football League from 1980 to 1997. Clinical information was obtained on 19 of 29 players who sustained orbital fractures. The most common signs and symptoms included decreased visual acuity (74%, 14), decreased eye movement (42%, 8), hyphema (37%, 7), and infraorbital numbness (21%, 4). The mechanisms of injury were a digital poke (74%, 14) and blunt facial trauma (26%, 5). There were significantly more orbital fractures than zygomatic fractures suffered by offensive linemen as compared with all other positions. Fifteen of 19 players were managed with surgical reconstruction; 4 players were treated nonoperatively. The mean time from injury to surgical procedure was 7.7 days (range, 0 to 42). The mean interval to follow-up was 45.6 months (range, 3 to 146). At follow-up examination, eight (53%) of the patients treated surgically still reported diplopia with upper field gaze. Three of the four patients treated nonoperatively were asymptomatic. The mean time lost from games or practice was 25 days (range, 5 to 56). Ultimately, 17 (89%) players with orbital fractures were able to return to full football activities. Two patients were unable to resume their careers because of residual visual impairment. PMID- 11206258 TI - Correlation of anthropometric measurements, strength, anterior cruciate ligament size, and intercondylar notch characteristics to sex differences in anterior cruciate ligament tear rates. AB - We performed a prospective study based on the hypothesis that physiologic differences exist between men and women in strength after adjustments for body weight; that the size of the anterior cruciate ligament is proportionate to the strength of its antagonists, the quadriceps muscles; and that women have a relatively small anterior cruciate ligament, thus predisposing them to a disproportionate number of anterior cruciate ligament injuries. One hundred matched high school basketball players, 50 male and 50 female, were evaluated with anthropometric measurements, body fat analysis, muscle strength evaluation, and magnetic resonance imaging measurements of the intercondylar notch and cross sectional area of the anterior cruciate ligament at the outlet. The male players were taller and heavier than their female counterparts, although they had 11% less body fat. Male players had statistically greater quadriceps and hamstring muscle strength than female players, even when adjustments were made for body weight. With adjustments for body weight, the size of the anterior cruciate ligament in girls was found to be statistically smaller than in boys. There was no statistically significant difference in the notch width index between the sexes. The study data support our hypothesis that sex differences in anterior cruciate ligament tear rates are caused primarily by several interrelated intrinsic factors. Most importantly, stiffness and muscular strength increase stress on the anterior cruciate ligament in female athletes. The anterior cruciate ligament, when adjustments have been made for body weight, is smaller in female athletes, and therefore, probably does not compensate for the lack of stiffness and strength. PMID- 11206259 TI - Mechanical evaluation of a soft tissue interference screw in free tendon anterior cruciate ligament graft fixation. AB - In this study of bioabsorbable screw fixation of free tendon grafts used in anterior cruciate ligament reconstruction, we performed load-to-failure and cyclic loading of tendon fixation in porcine bone. Bone density measurements from dual photon absorptometry scans were obtained to correlate bone density with fixation failure. The average density of porcine bone (1.42 g/cm2) was similar to that of young human bone (1.30 g/cm2) and significantly higher than that of elderly human cadaveric bone specimens (0.30 g/cm2). Cyclic loading was performed on free tendon grafts fixed with a bioabsorbable screw alone and on grafts fixed with a bioabsorbable screw and an anchor (polylactic acid ball or cortical bone disk). Stiffness of fixation increased substantially with the addition of a cortical bone disk anchor or polylactic acid ball compared with the interference screw alone. Tensile fixation strength of central quadriceps free tendon and hamstring tendon grafts were significantly superior in porcine bone of density similar to young human bone than in elderly human cadaveric bone. The bioabsorbable interference screw yielded loads at failure comparable with traditional bone-tendon-bone and hamstring tendon fixation when controlled for bone density. The addition of a cortical bone disk anchor provided the most optimal fixation of free tendon with the bioabsorbable screw and reduced slippage with cyclic loading to a very low level. PMID- 11206260 TI - Sagittal plane knee translation and electromyographic activity during closed and open kinetic chain exercises in anterior cruciate ligament-deficient patients and control subjects. AB - Using electrogoniometry and electromyography, we measured tibial translation and muscle activation in 12 patients with unilateral anterior cruciate ligament injury and in 12 control subjects. Measurements were made during an active extension exercise with 0-, 4-, and 8-kg weights and during squats on two legs and on one leg where the projection of the center of gravity was placed over, behind, and in front the feet. In the uninjured subjects, tibial translation increased with increasing load except during the squat with the center of gravity behind the feet, which produced the smallest translation. For the active extension exercises, translation was greater during eccentric activity. In the anterior cruciate ligament-injured knees, all squats resulted in similar translation, which was smaller than that during the active extension exercise. The highest muscle activation was seen during squats. Hamstring muscle activity was low. Increased static laxity in the anterior cruciate ligament-deficient knee can be controlled during closed but not during open kinetic chain exercises. Coactivation of the quadriceps and gastrocnemius muscles seems to be important for knee stability, whereas hamstring muscle coactivation was insignificant. To minimize sagittal translation during nonoperative management of anterior cruciate ligament-deficient knees, closed kinetic chain exercises are preferable to open kinetic chain exercises, and importance should be attached to the spontaneous coactivation of the quadriceps and gastrocnemius muscles. PMID- 11206261 TI - Direct evidence of the anterior cruciate ligament-hamstring reflex arc in humans. AB - It has been emphasized that the anterior cruciate ligament plays an important role in the proprioceptive feedback system. The anterior cruciate ligament hamstring reflex has been revealed in animal experiments, but it has not been established in humans. The purpose of this study was to demonstrate direct evidence of the anterior cruciate ligament-hamstring reflex arc. Nine knees in nine healthy subjects were investigated. The anterior cruciate ligament was stimulated by the use of wire electrodes inserted using an arthroscopic technique. Electromyographic signals from the biceps femoris and the semitendinosus muscles were recorded with surface electrodes. The change in electromyographic activity was analyzed after electrical stimulation in the normal knee condition, and again after intraarticular sensation had been interrupted with a local anesthetic. After electrical stimulation, subjects demonstrated increased electromyographic activity of the hamstring muscles in the normal knee condition. This response indicates the existence of an anterior cruciate ligament-hamstring reflex arc. Conversely, there was no change in activity for the hamstring muscle in the anesthetized knee because the afferent impulse from the neural elements of the anterior cruciate ligament had been removed. PMID- 11206262 TI - The effects of patellar taping on patellofemoral incongruence. A computed tomography study. AB - Patellar taping for the purpose of patellar medialization is a nonoperative rehabilitation technique used in the treatment of patellofemoral pain. Despite early reports of excellent success rates, the indications for this treatment and its efficacy on patellofemoral pain are unclear. The present computed tomography study was undertaken to evaluate the effect of patellar taping on patellofemoral incongruence. Sixteen female patients (age range, 16 to 25 years) with anterior knee pain related to patellofemoral incongruence underwent computed tomography examination with their quadriceps muscles relaxed and contracted both before and after patellar taping. Patellar lateralization was measured as lateral patellar displacement, and patellar tilt was measured as lateral patellar angle. Patellar taping did not significantly affect patellofemoral lateralization or tilt. The results of this study do not support the use of this method for passive correction of patellofemoral incongruence. Although patellar taping may well be effective in controlling anterior knee pain during physical therapy, it does not do so by medializing the patella. PMID- 11206263 TI - The effects of time course after anterior cruciate ligament injury in correlation with meniscal and cartilage loss. AB - In this study, 130 consecutive patients with anterior cruciate ligament insufficiency who were undergoing ligament reconstruction underwent arthroscopic examination at the time of reconstruction, and any loss of meniscal or chondral integrity was documented in a systematic fashion. In these patients, a greater proportion of the medial meniscus was lost compared with the lateral meniscus (16% versus 5%). On average, 6 cm2 of the articular cartilage was damaged (5.2 cm2) or lost (0.8 cm2), with the area of damage and loss greatest on the medial femoral condyle. Patients whose injuries had occurred more than 2 years before the examination had more than sixfold greater cartilage loss and damage compared with those whose injuries had occurred within the past 2 months. Meniscal loss was associated with a threefold increase in cartilage damage or loss. The group of patients with meniscal loss whose initial anterior cruciate ligament injury occurred more than 2 years before examination exhibited 18 times the amount of cartilage loss or damage as did the group that had no meniscal loss and whose injury occurred less than 1 month before examination. PMID- 11206264 TI - Subluxating biceps femoris tendon: an unusual case of lateral knee pain in a soccer athlete. A case report. PMID- 11206265 TI - Complications associated with the use of meniscal arrows. PMID- 11206266 TI - PET in neuro-oncology. AB - This article reviews possible clinical applications of positron emission tomography (PET) in brain tumor patients. PET allows quantitative assessment of brain tumor pathophysiology and biochemistry. It therefore provides different information about tumors when compared to histological or neuroradiological methods. Common clinical indications for PET comprise tumor delineation and identification of the metabolically most active tumor regions (target for biopsy, differentiation of viable tumor from necrosis). Further, the spatial relation between brain activated e.g., by speech, and the tumor bulk can be explored by activation studies. PET could also aid in the prediction of treatment response by measurement of tumor perfusion or hypoxia. Moreover, PET tracers could identify treatment targets e.g., gene products. The latter topic has not been systematically evaluated in human patients. PMID- 11206267 TI - Fas receptor counterattack against tumor-infiltrating lymphocytes in vivo as a mechanism of immune escape in gastric carcinoma. AB - We investigated the presence and functional status of surface expression of the Fas receptor (FasR) and its ligand (FasL) in tumor and tumor-infiltrating lymphocytes (TIL) in gastric carcinoma (n = 36) from the primary locus, metastatic gastric carcinoma (n = 30) from malignant ascites, and benign gastric mucosa (n = 30) for the control. The quantitative analysis was based on the percentage of positive cells by a flow cytometry. The results showed that the membrane-bound FasL molecule was constitutively expressed in primary and metastatic gastric carcinomas as well as normal gastric epithelium in nearly all the patients. In particular, metastatic carcinoma proved to aberrantly express the FasL molecule. On the other hand, FasR expression ranged from minimal or absent in primary and metastatic gastric carcinomas, suggesting that the carcinoma might be rendered less sensitive toward FasR-induced killing. Apoptotic tumor cells detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick and labeling (TUNEL) were barely identified in primary and metastatic carcinomas. In the analysis of TIL, the expression of FasR and FasL, and apoptotic TIL could not usually be observed in primary gastric carcinoma. In metastatic carcinoma, however, there was significant overexpression of FasR and FasL in immune TIL associated with a higher frequency of apoptotic cell death detected by TUNEL. The results suggest that metastatic carcinoma expressing FasL, but not FasL+ primary carcinoma, might evade the immune attack by apoptotic depletion of activated TIL through the FasR/FasL systems. These results provide the direct and quantitative evidence of FasR counterattacks and/or paracrine fratricides as a mechanism of tumor-immune escape in vivo in human cancer. PMID- 11206268 TI - Efficient tumor regression induced by genetically engineered tumor cells secreting interleukin-2 and membrane-expressing allogeneic MHC class I antigen. AB - PURPOSE: To analyze the immunotherapeutic potentials of genetically engineered tumor cells secreting IL-2 and a membrane-expressing allogeneic MHC class I molecule Kb in a murine hepatoma model. METHODS: In order to express both genes in coordination in the target cells, we constructed a polycistronic retroviral vector containing Kb, IL-2, and NeoR genes using two internal ribosome entry sites (IRES). Tumor growth was carried out by implantation of transduced tumor cells into mouse, while anti-tumor effects were demonstrated by the treatment of established tumors. The infiltrated cells were analyzed by immunohistochemistry. RESULTS: The combined effect of IL-2 secretion and alloantigen expression on immunostimulation was demonstrated by the rejection of transduced tumor cells. In the treatment of established tumors, the Kb/IL-2 co-expressing tumor cells induced strong anti-tumor immunity, superior to that induced by the single gene transduced cells. The increased diversity of infiltrated cell types in tumor sites indicated that both a specific and non-specific immune response had been activated. CONCLUSION: Our study provides evidence that tumor cells with IL-2 secretion and membrane-expression of allogeneic MHC class I antigen are capable of inducing both strong tumor rejection and immunity. PMID- 11206269 TI - Dietary cancer risk from conditional cancerogens (tumor promoters) in produce of livestock fed on species of spurge (Euphorbiaceae). IV. Toxicologic and pathophysiologic observations in lactating goats and their suckling kids fed on the irritant herbs Euphorbia nubica and Euphorbia helioscopia: an etiologic model for investigations on the putative risk of cancer by consumption of food p. AB - The feeding of lactating goats on usual green fodder, contaminated with Euphorbia helioscopia or E. nubica, results in poisoning of the dams as well as their suckling kids. General signs of toxicity were emaciation, depression, shedding of body hair, arching of back, and possible death. Post-mortem changes of dams and dead suckling kids included congestion and hemorrhage in cardiac muscle, lung, liver, and kidneys. Blood analyses of goats exposed to these contaminants showed an increased level of serum alanine amino transferase compared to control samples, indicating cellular destruction in the liver. The latter was confirmed by histopathological changes in the organ which include severe congestion, necrosis, and degenerative changes. The goats also suffered from deterioration of renal function as indicated by increased blood urea nitrogen and creatinine levels. In histopathologic inspections of kidney, severe congestion, hemorrhage in the cortex and medulla, as well as necrosis of epithelial cells of kidney tubules were noticed. Considerable degenerative changes were also observed in heart and lung. The pathophysiological appearances indicate that by feeding on the Euphorbia species mentioned above, the goats are poisoned in a way similar to the case of E. peplus reported previously. Such intoxication most likely is due to irritant and hyperplasiogenic diterpene ester (DTE) toxins, usually present in the aerial parts of Euphorbia species and well known as tumor promoters in mouse skin. After ingestion of the toxic plant parts by the goats, the DTE toxins might be metabolized and thereby partially detoxified. Yet, at least in part, they may show up in the milk of the goats, as indicated by severe poisoning of their suckling kids. As discussed previously in lactating goats fed on fodder contaminated with E. peplus, tumor promoters of the DTE type may enter the human food chain via this source of milk. Such milk may be considered a valuable etiologic model for the investigation of economic, ecologic, and public health problems raised by human diet polluted with tumor promoters, i.e., conditional (non-genotoxic) cancerogens. PMID- 11206270 TI - Dietary cancer risk from conditional cancerogens (tumor promoters) in produce of livestock fed on species of spurge (Euphorbiaceae). V. Skin irriitant and tumor promoting diterpene ester toxins of the tigliane and ingenane type in the herbs Euphorbia nubica and Euphorbia helioscopia contaminating fodder of livestock. AB - Irritant diterpene ester toxins were isolated from Euphorbia nubica and E. helioscopia, which are contaminants of the green fodder of livestock in Egypt. Fractionations of methanol extracts of aerial parts of both plants were monitored by the irritation unit on the mouse ear. Plant extracts were subjected to multiplicative distribution methods, yielding irritant hydrophilic fractions that were further purified by column chromatography. Final purification of the materials was achieved by TLC (silica gel) followed by HPLC, or by TLC alone. In this way, from E. nubica, five Euphorbia factors (Nu1-Nu5) were isolated and characterized as short-chain polyfunctional diterpene esters of tigliane-type parent alcohols. The two weak irritants Nul and Nu3 were triesters of 4 deoxy(4alpha)phorbol. Nu2 was shown to be a triester of the stereoisomeric tigliane-type parent alcohol 4-deoxyphorbol. Weak irritant Nu4 probably is a positional isomer of Nu2. Nu5 was characterized as a short-chain triester of 4,20 dideoxy-5xi-hydroxyphorbol. From E. helioscopia, six short- to medium-chain polyfunctional diterpene esters of the ingenane type, generally containing unsaturated acids were obtained, i.e., four irritant esters of ingenol (Euphorbia factors H1, H2, H5, and H6) and two esters of 20-deoxyingenol (non-irritant Euphorbia substance HS4, and irritant Euphorbia factor H8). All irritant Euphorbia factors of the tigliane and ingenane diterpene ester type described in this investigation are considered to be more or less active tumor promoters, i.e., conditional (non-genotoxic) cancerogens. The Euphorbia factors assayed exhibited moderate (H1) to low (H8) relative tumor-promoting potency in comparison to the ingenane prototype DTE tumor promoter 3-TI. PMID- 11206271 TI - Bendamustine monotherapy in advanced and refractory chronic lymphocytic leukemia. AB - Bendamustine, an alkylating agent without cross-resistance to cyclophosphamide is active in a variety of lymphoproliferative and other malignancies. In an open phase-II study we treated 23 patients with a median age of 62 years at study entry (43-86 years) with advanced, refractory or relapsed (Rai stage III n = 9, Rai stage IV n = 14) chronic lymphocytic leukemia (CLL) with bendamustine. At study entry, only 13 patients were chemotherapy-naive. The treatment schedule with bendamustine was as follows: for patients up to 70 years 60 mg/m2 for 5 days, for patients over 70 years 50 mg/m2 for 5 days, repetition at day 29. Remission criteria were used according to Cheson et al. (1996). All patients were evaluable for toxicity and 20 for response. An objective remission was achieved in 15/20 patients (75%), including six patients with complete remission (CR). Three of the complete responders had no chemotherapy prior to bendamustine. No change (NC) occurred in 5/20 patients (25%). Median overall survival after bendamustine treatment is 13.6 months (1-46 months) and 16.6 months (1-46 months) in patients responding to bendamustine. In total, 74 courses of bendamustine were applied. Therapy-related anemia and thrombocytopenia were rare. However, WHO grade III/IV leukocytopenia occurred in 38/74 cycles (51%), resulting in treatment-related mortality in 3/23 patients (13%). These patients were severely immunocompromised due to pretreatment or the underlying disease. As a corollary of the study, a general prophylactic antibiotic treatment (trimethoprim/ sulfamerazine) was instituted. A general feature was the decline of the CD4/CD8 ratio: mean before therapy: 1.36; after two courses: 0.98; after four courses: 0.6, as documented in all patients who received at least two courses of bendamustine (n = 12). All evaluable patients showed a decline in the CD4/8 ratio. However, this decline was not clearly related to an increased risk of infectious episodes. We observed mainly cutaneous allergic reactions (three WHO grade I; one WHO grade II) leading to a cessation of bendamustine treatment in 4/23 patients (18%). Bendamustine is highly effective in advanced or refractory CLL. In multiple pretreated or otherwise severely immunocompromised patients bendamustine might lead to additional immunosuppression with subsequent infectious complications. PMID- 11206272 TI - Neurotoxicity associated with a regimen of carboplatin (AUC 5-6) and paclitaxel (175 mg/m2 over 3 h) employed in the treatment of gynecologic malignancies. AB - While the combination chemotherapy regimen of carboplatin (AUC 5-6) and paclitaxel (175 mg/m2 over 3 h) is widely employed in the treatment of ovarian cancer, there are limited data available in the oncologic literature regarding the neurotoxic potential of the program. We retrospectively reviewed the clinical course of 87 patients treated in the Gynecologic Cancer Program of the Cleveland Clinic Taussig Cancer Center to address this important clinical issue. The overall incidence of peripheral neuropathy in this population was 25%, with 13% of women experiencing symptoms > or = grade 2 in severity. We conclude that while neurotoxicity is common following the use of this regimen, significant neurological dysfunction (> or = grade 2) is relatively infrequent. PMID- 11206273 TI - A comparative study of the clinicopathological significance of E-cadherin and catenins (alpha, beta, gamma) expression in the surgical management of oral tongue carcinoma. AB - PURPOSE: E-cadherin and catenins are important epithelial adhesion molecules in normal epithelium. Loss of E-cadherin-catenin adhesion is an important step in the progression of many epithelial cancers. E-cadherin and catenins expression in carcinoma of the tongue were evaluated in relation to their clinicopathological features and prognostic values. METHOD: Immunohistochemical staining was carried out with E-cadherin and (alpha, beta, gamma)-catenin monoclonal antibodies for 85 surgical specimens of oral tongue carcinoma, nine matched metastatic lymph nodes, and seven locally recurrent tumours. RESULTS: There was under-expression in 85% of E-cadherin, 94% of alpha-catenin, 89% of beta-catenin, and 83% of gamma catenin in the primary tumours. There was no correlation of E-cadherin/catenin expression with sex, age, cancer stage, and differentiation. Nodal metastasis was found in 68% of patients with weak expression of gamma-catenin compared with 9% with strong expression in primary tumours (chi-square, P = 0.02). E-cadherin was a significant prognostic factor for survival and recurrence; patients with weak E cadherin expression had 53% 5-year survival compared with 85% with strong expression (Wilcoxon, P = 0.0159). CONCLUSIONS: Both E-cadherin and catenins were highly under-expressed in oral tongue carcinoma, metastatic lymph node, and recurrent tumour. gamma-catenin had predictive value for nodal metastasis. E cadherin was, however, a more important prognostic factor for recurrence and survival. PMID- 11206274 TI - Carboplatin pharmacokinetics in patients receiving carboplatin and paclitaxel/docetaxel for advanced lung cancers: impact of age and renal function on area under the curve. AB - PURPOSE: To further define the most appropriate way of choosing the dose of carboplatin. PATIENTS AND METHODS: The pharmacokinetics of carboplatin were analyzed in 30 patients with advanced lung cancer receiving a total of 48 cycles of carboplatin plus paclitaxel/ docetaxel combination chemotherapy. Platin concentrations of ultrafiltrated plasma and urine samples were determined by flameless atomic absorption spectrometry. A multiple regression analysis was performed for interactions between pharmacokinetic parameters and pretreatment characteristics. RESULTS: Using a twocompartment-model, the following parameters were obtained (mean, coefficient of variation): initial half-life, 0.903 h (48%); terminal half-life, 13.6 h (116%); maximum plasma concentration (Cmax), 38.5 microM (86%); AUC, 111.9 microM/h (86%); volume of distribution, 411 l (130%); total clearance (Ct), 579 ml/min (75%); renal clearance (Cr), 453 ml/min (80%); renal elimination, 76% of dose (17%). In the univariate analysis, age was significantly related to Cmax (P = 0.0303), AUC (P = 0.0050), Ct (P = 0.0020), Cr (P = 0.0092). Plasma creatinine (Crp) was related to Cmax (P = 0.0228), and 1/[Crp] was related to Cmax (P = 0.0015) and AUC (P = 0.0054), while body weight was related to Cmax (P = 0.0365). No interaction with the schedule of application of the two drugs was observed. In the multivariate analysis, factors significantly related to AUC were 1/[Crp] (P < 0.01) and age (P < 0.01). Crp (P < 0.05) and 1/[Crp] (P < 0.01) were significantly associated with Cmax. CONCLUSIONS: These data stress the importance of dosing carboplatin according to renal function and age and warrant further analyses to validate this concept prospectively. PMID- 11206275 TI - Combination cancer chemoprevention with green tea extract and sulindac shown in intestinal tumor formation in Min mice. AB - Green tea is the most effective beverage for cancer prevention in humans. Looking at the concept of combination cancer chemoprevention, we previously reported the synergistic effects of (-)-epigallocatechin gallate (EGCG) with sulindac, and the additive effects of EGCG with tamoxifen, on cancer-preventive activity in human lung cancer cell line PC-9. This paper reports confirmation of the synergistic effects of EGCG with sulindac on the inhibition of intestinal tumors in multiple intestinal neoplasia (Min) mice. Treatment with both green tea extract and sulindac significantly reduced the number of tumors from 72.3 +/- 28.3 to 32.0 +/ 18.7 tumors per mouse, a decrease of 44.3%, whereas treatment with green tea extract alone or with sulindac alone reduced it to 56.7 +/- 3.5 and 49.0 +/- 12.7, respectively. The results also indicated that green tea extract inhibited tumor growth in Min mice almost as potently as sulindac itself did. The three treated groups did not show any adenocarcinomas, whereas 10.8% of the control group did. Since cancer-preventive agents like sulindac and tamoxifen are associated with adverse effects, we discuss the possibility of non-toxic, combination cancer chemoprevention with green tea, looking at the goal of truly effective cancer prevention. PMID- 11206276 TI - Epidemiologic aspects of cancer prevention in Germany. AB - In Germany, as in other highly industrialized countries, cancer is the second most common cause of death. With approximately 210,000 individuals dying each year from malignant tumours, roughly one in four deaths in Germany can currently be attributed to cancer. Only in the past few years has there been a slow decline in the age-standardized mortality rates for cancer, even among men. This follows a long period of some decades, during which the mortality steadily increased and then persisted at a high level. The reversal, however, does not mean that the situation is no longer a cause for concern. In fact, for the most common cause of death, namely the cardiovascular diseases, a much greater decrease in mortality has been observed for many years now. If this trend continues, cancer could become the largest killer in another 15 to 20 years. On the other hand, we have been aware since the end of the 1960s that the majority of cancers are caused by environmental influences and are thus, in principle, avoidable. In the present contribution we present: (a) the fundamental arguments to support the thesis that a large proportion of cancers, and of cancer deaths, could be avoided; and (b) an estimate for Germany of both the theoretical potential of primary cancer prevention and also the practically attainable potential. The estimates are based on very conservative assumptions. They yield, for the theoretical potential, values in the range 43-65% and for the reduction actually obtainable in the medium term due to primary prevention, values of 18-31%. PMID- 11206277 TI - Short-term plasticity of extrinsic excitatory inputs to neocortical layer 1. AB - Previous studies have shown that different pyramidal cell inputs vary in the short-term plasticity expressed when they are subjected to repetition of use. Here, we describe short-term plasticity at synapses that mediate long-range input to neocortical layer 1 and compare it with that which normally occurs in the hippocampal Schaffer collateral pathway, which also involves projection by remote inputs onto apical dendrites. We isolated tangential inputs to layer 1 in neocortical slices, stimulated these with brief 40-Hz trains, and examined postsynaptic responses by recording extracellularly from layer 1 in somatosensory, prefrontal, and visual neocortex, and intracellularly from visually identified pyramidal cell somata in layer 2/3 in somatosensory and prefrontal neocortex. Train response amplitudes were characterized by calculating paired-pulse ratios, fifth-versus-first amplitude ratios (5th/1st ratios), and a center-of-mass index "M". As expected, the hippocampal train responses facilitated strongly. In contrast, layer-1 responses displayed strong synaptic depression in all regions examined. This depression was reflected in 5th/lst ratios and M scores, but not paired-pulse ratios because it did not consistently begin until the third responses in trains. It persisted unchanged in the presence of partially blocking levels of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), but was converted to strong facilitation when slices were bathed in low-Ca++ media. Intracellularly, we observed response-train depression very similar to that recorded extracellularly. These findings show that long-range inputs to neocortical layer 1 display short-term plasticity markedly different from that which normally occurs at hippocampal Schaffer collateral synapses, but similar to that which has been described previously for excitatory inputs to pyramidal cells in deeper neocortical layers. PMID- 11206278 TI - Thalamocortical arbors extend beyond single cortical barrels: an in vivo intracellular tracing study in rat. AB - Neurons in layer IV of rat somatosensory (SI) barrel cortex receive punctate somatic input from well-defined regions of the periphery. Following peripheral deafferentation, SI neurons in deafferented cortex respond to new input from neighboring regions of the skin surface. The precise mechanism(s) through which this occurs is unknown, although corticocortical and barreloid to barrel connections have been suggested as possible substrates. Because layer-IV barrels receive a strong afferent input from ventroposterior (VP) thalamic projection neurons, any divergence in the thalamocortical (TC) projection to multiple cortical barrels could also provide an anatomical substrate for rapid cortical reorganization. We used in-vivo intracellular recording methods to record and physiologically identify neurons in rat VP and to label those neurons with an intracellular tracer. Thalamic neurons (n=117) were impaled with sharp intracellular electrodes, and the receptive field(s) and firing pattern were measured. Cells were then injected with biocytin or biotinylated dextran amine (BDA). A total of 38 labeled TC neurons were quantitatively analyzed for soma size and dendritic arborization size; quantitative analysis of TC-axon arborizations in layer IV of barrel cortex was carried out in a total of 13 TC neurons. Two different axon-arborization patterns were identified in SI cortex: direct-projecting axons (n=6) were observed to project to and arborize within a single cortical barrel as well as extend their fibers into adjacent barrels; bifurcating-type axons (n=7) were seen to bifurcate in the subcortical white matter or in layer VI and then project to multiple barrel columns, where they arborized in layer IV. Axon fibers were always observed in three or more cortical barrels (mean=5, range=3-7). The mean mediolateral extent of arborizations in layer IV for the direct-projecting and bifurcating type axons were 458 microm and 1,302 microm, respectively, and these were significantly different (t=3.78, P<0.01). Axon-fiber length within cortical laminae was measured for each arborization pattern in relationship to the total fiber length within a cortical column. Direct-projecting axons always had greater than 50% of their fiber length within layer IV. Bifurcating-type axons were differentially distributed within multiple columns and always had less than 50% of their total column fiber length in layer IV. Morphological analysis of TC somata and dendrites revealed no correlation between local neuron morphology and axonal-arborization patterns. All intracellularly recorded TC neurons had similar adapting firing patterns when injected with a long-duration pulse. Our results showed that TC neurons project to multiple cortical barrels with one barrel receiving the principal input. This divergent TC projection pattern in SI cortex may provide an anatomical substrate for cortical plasticity and must be considered in any mechanism of rapid cortical reorganization. PMID- 11206279 TI - Canal-otolith interaction in the fastigial nucleus of the alert monkey. AB - To determine the contribution of the otoliths as well as the horizontal and vertical semicircular canals to the response of "vestibular only" neurons in the rostral fastigial nucleus of the alert monkey, we applied natural sinusoidal vestibular stimuli (0.6 Hz; +/-15 deg) around different axes. During the experiment the monkey sat erect in a primate chair with the head immobile. Semicircular canal responses were investigated during tilted yaw stimulation around an earth vertical axis. The tilt angle was varied by 30 deg and included the optimal plane for horizontal canal stimulation (15 deg nose down from the stereotactic plane). The otoliths and mainly the vertical canals made contributions during stimulation around an earth-fixed horizontal axis (vertical stimulation). Head orientation was also slowly altered (2-3 deg/s) over a range of 180 deg under both stimulus conditions (tilted yaw and vertical stimulation). Neuronal data for each paradigm were fitted by a least squares best-sine function. Computation of the hypothetical contributions made by all three pairs of semicircular canals and the otoliths to these responses showed that 74% of the 46 neurons investigated received an otolith input; in most instances it was combined with a canal input. Neurons most often received input from the horizontal and vertical canals as well as the otoliths. Only a minority of neurons received a purely otolith (13%), vertical canal (13%), or horizontal canal (4%) input. Conventional criteria (head position-related activity, spatiotemporal convergence, STC) failed to detect an otolith contribution in several such instances. Thus, canal-otolith convergence is the general rule at this central stage of vestibular information processing in the fastigial nucleus. The large variety of response types allows these neurons to participate in multiple tasks of vestibulospinal movement control. PMID- 11206280 TI - Postnatal development of biotinylated dextran amine-labeled corpus callosum axons projecting from the visual and auditory cortices to the visual cortex of the rat. AB - The distribution and morphology of developing corpus callosum (CC) axons in rat visual cortex was studied by unilateral application of the in vivo anterograde tracer biotinylated dextran amine (BDA) to the visual or auditory cortex of newborns through adults. Changes in the distribution and morphology of CC axons during development were observed. Following BDA placement only in visual cortex, nearly all CC projections were to visual cortex (homotopic CC projections). At postnatal day (PND) 5-8, labeled CC axons were found throughout the contralateral visual cortex, including area 17; these CC axons could be followed from the white matter to layer I. By PND 13, few CC axons were found in medial area 17, indicating the existence of transitory CC axons in area 17 at younger ages. Morphological changes were investigated at the area 17/18a border and showed that CC axon collaterals were not formed until PND 8, and terminal arbors were not visible until PND 13; by PND 17, the adult CC-axon terminal pattern was present. At all ages, only a few heterotopic CC projections from visual to auditory cortex were found in the gray matter, although many labeled CC axons extended laterally into the white matter underlying the auditory cortex. Following BDA placement only in auditory cortex, CC projections to both auditory (homotopic CC projections) and visual (heterotopic CC projections) cortex were observed. At all ages, the homotopic CC projections were present throughout the auditory cortex, but were not distributed homogeneously; densely labeled CC axons showed a distinct columnar organization. The heterotopic CC projections were present in all visual cortical areas, including medial area 17, in significant numbers until PND 24, but were mostly eliminated by PND 28, at which time a labeling pattern similar to the adult was found. Thus, most of the heterotopic CC projections were transitory. The present study confirms the existence of transitory CC axons projecting through all layers of the visual cortex, as revealed by DiI, and extends the DiI results by showing that these transitory CC axons arise from both homotopic and heterotopic origins. Furthermore, different sources of transitory CC axons have different timetables for elimination. PMID- 11206281 TI - Passive finger movement evoked fields in magnetoencephalography. AB - We studied neuromagnetic fields during passive finger movements in 11 normal subjects. Activation started 27 ms after the onset of movement and remained for about 100 ms. Four activation maxima occurred within this time range, PM1 at 27 ms, PM2 at 46 ms, PM3 at 85 ms, and PM4 at 125 ms. Not all components were distinguishable in every subject partly due to overlapping effects, but PM3 was present in all subjects. Magnetic source imaging (MSI) revealed dipolar sources within 1 cm of the central sulcus for all four components. The results suggest that studying the integrity of the sensorimotor system in patients regardless of their degree of motor impairment is feasible. PMID- 11206282 TI - Eye-head coordination and the variation of eye-movement accuracy with orbital eccentricity. AB - Different humans vary widely in the tendency to move the head during saccadic shifts in gaze. The reasons for this variation are unknown. Because combined eye head movements are associated with a recentering of the eyes in the orbits, humans who are "head movers" tend to maintain the eyes within a narrower range than do non-head movers. We explored the possibility that variations in the ability to control eye movements at eccentric positions lead to variations in customary ocular motor range and, by extension, explain the variations in head movement tendencies. We studied ten normal adults. In each, we measured the full scale ocular motor range and customary ocular motor range (the eccentricity range within which the eye was found at the conclusion of eye- or eye-head saccades). We also determined the eye-only range, the orbital range within which the probability of a head movement accompanying a gaze shift was low. Customary, eye only, and full-scale ranges spanned (mean +/-SD) 41.1+/-16.9 degrees, 30.2+/-18.8 degrees, and 92.8+/- 9.1 degrees, respectively. We then assessed variations in kinematics of several ocular motor behaviors as functions of eye eccentricity. The stable fixation range, defined by the range over which drift velocities were below 1 degree/s, spanned 81.1+/-11.2 degrees in the light and 69.5+/-21.5 degrees in the dark. The range over which the gains of the vestibulo-ocular reflex in the light and smooth pursuit approached their values at zero eccentricity spanned 66.3+/-7.1 degrees and 69.0+/-10.0 degrees, respectively. Small centrifugal saccades (5-10 degrees) tended to become either slowed or hypometric with increasing eccentricity. Sensitive to both slowing and hypometria, the ratio of peak gaze velocity to target shift amplitude was flat over a range spanning 65.7+/-14.9 degrees. Finally, the ranges over which the initial saccade placed the fovea upon the target averaged 35.5+/-10.7 degrees for eye-only saccades and 36.6+/-15.0 degrees for eye-head saccades. With the exception of the range of stable fixation in the light, the kinematic ranges were either unrelated or inconsistently related to full-scale range, indicating that the deterioration of eye movements with increasing ocular eccentricity is not a simple consequence of the eyes encountering the limits of their excursion. None of the kinematic ranges correlated positively with customary or eye-only range. Thus, while head movements may be orchestrated so as to maintain the eyes within a desired range, that range (and thus head movement tendencies) is not predicated upon the range of ocular eccentricity over which eye movements are accurately controlled. PMID- 11206283 TI - Abnormal vestibular control of gaze and posture in a strain of a waltzing rat. AB - The waltzing behavior is usually attributed to vestibular dysfunction. However, the vestibular control of gaze and posture has not yet been measured quantitatively in any waltzing mutant. Therefore, this study was aimed at investigating the relationship between inner-ear morphology, the circling behavior, and the vestibular control of gaze and posture in a new strain of waltzing rats. Light- and electron-microscopy studies of these mutants did not reveal any structural abnormalities of the vestibular neural epithelia. In addition, the expression of Calretinin and 200-kD phosphorylated and non phosphorylated neurofilaments was also found to be normal in the vestibular neural epithelia and ganglion cells. In contrast, the mutants showed severe dysfunctions of the vestibular control of gaze and posture. The skeletal geometry of the alert unrestrained animals was studied using cineradiography. At rest, waltzing rats held their heads tilted down: the horizontal semicircular-canal's plane was near the earth-horizontal's plane, instead of being tilted up as in Long Evans control rats. In addition, their cervical column was pitched more forward (33.6 degrees) than in the control group (6.9 degrees). The circling behavior was observed frequently, and the rats had episodes of circling in both directions. The episodes of circling amounted to an average of 17 turns, and the average angular velocity of the circling was 645 degrees/s. Unilateral labyrinthectomy induced the same postural and oculomotor syndromes in the waltzing and control groups. This indicates that the mutant vestibular nerve had a significant resting discharge before the lesion. Eye movements were recorded using acutely implanted search coils. Although waltzing rats were able to perform normal spontaneous eye movements, they showed a complete deficit of the horizontal vestibulo-ocular reflex (HVOR) and an impairment of the maculo-ocular reflex (MOR) during constant velocity, off-vertical axis rotation (OVAR). These results show, for the first time, that deficient transduction and/or processing of the horizontal-canal- and macular-related information can be causally related to the circling behavior and abnormal posture, respectively. PMID- 11206284 TI - How sensitive is hand transport to illusory context effects? AB - A recent report that hand transport was sensitive to a size-contrast illusion (SCI) implied that the distinction between visual processing for perception versus action might only affect visual information obtained late during reaching. In this study, the presence of a perceptual SCI did not affect reaction time, movement time, or movement amplitude. However, both perception and action became sensitive to the SCI with memory-based responses. It is concluded that the distinction between visual processing for perception versus action does extend to hand transport. Immediate action is entirely based on veridical visuo-motor representations, whereas even slightly delayed actions begin to reflect distorted perceptual representations. PMID- 11206285 TI - Spatial and temporal control of trunk-assisted prehensile actions. AB - The present study utilized a trunk-assisted prehension task to examine the hypothesis that there is spatial regularity between the grasp and transport components. To test this hypothesis, we varied movement amplitude, reach speed, and object size. When examining the opening and closure phases of aperture formation, it was found that the distance to peak aperture increased systematically with hand-path trajectory length, while the distance from peak aperture to the object remained constant, which supports the notion of state space control. Regarding the relationship among the body segments involved, temporal measures such as relative time to peak aperture, and peak velocity of the arm and trunk were altered by the changes in both object size and reach speed. It was also found that the time to peak trunk velocity was coupled with the time to peak arm velocity as well as with the time to peak aperture. Based on these results, it appears that the trunk is closely linked not only to the arm motion, but also to the aperture formation. Collectively, these findings suggest that, during trunk-assisted prehension, the arm and the trunk are coordinated by neuromotor synergies that appear to position grip aperture for a stable closure to grasp the object. PMID- 11206286 TI - Reaching affects saccade trajectories. AB - The pre-motor theory suggests that, when attention is oriented to a location, the motor systems that are involved in achieving current behavioural goals are activated. For example, when a task requires accurate reaching, attention to a location activates the motor circuits controlling saccades and manual reaches. These actions involve separate neural systems for the control of eye and hand, but we believe that the selection processes acting on neural population codes within these systems are similar and can affect each other. The attentional effect can be revealed in the subsequent movement. The present study shows that the path the eye takes as it saccades to a target is affected by whether a reach to the target is also produced. This effect is interpreted as the influence of a hand-centred frame used in reaching on the spatial frame of reference required for the saccade. PMID- 11206287 TI - Initial evidence for the mixing and soft assembly of the ankle, suspensory, and hip muscle patterns. AB - The onset latencies of automatic muscle responses to backward translations of the support surface in standing subjects were assessed to test two longstanding hypotheses: that (1) the ankle, hip, and suspensory muscle patterns represent discrete synergies; and (2) the suspensory pattern cannot be mixed with the ankle and the hip patterns (based on theoretical modeling). Muscle responses were recorded at the leg (medial gastrocnemius and tibialis anterior), thigh (hamstring and quadriceps), lower trunk (paraspinals and abdominals), and the upper trapezius muscles. A principal factor analysis with orthogonal varimax rotation was conducted to describe the variation among the muscle onset latencies by means of the smallest possible set of newly defined variables, or factors. Muscles that were correlated with each other were grouped into a factor. The analysis produced three factors with eigenvalues > or =1, which accounted for 81% of the total variance. Based on the first muscle response in each factor, the muscle patterns resembled the hip, ankle, and suspensory synergies. Muscle responses within a synergy were activated before the completion of the muscle responses in the other synergies, indicating that the synergies, though mixed, are triggered separately. This is consistent with the hypothesis that the ankle, hip, and suspensory patterns represent discrete synergies. On the other hand, the results do not support the hypothesis that the three patterns cannot be combined. PMID- 11206288 TI - Pupillary response to chromatic flicker. AB - There is significant evidence for higher-level cortical control of pupillary responses to visual stimuli, suggesting that factors other than luminance changes may induce a pupillary response. In the present study, the pupillary responses to equiluminant flickering stimuli in a range of 3-13 Hz were examined. Flicker stimuli included color-black (luminance-modulated) and color-color (hue modulated) flicker. Equiluminance was determined both by objective luminance measures as well as by subjective, perceptual equiluminance for each subject. For both objectively and subjectively equiluminant flicker, significant, sustained pupillary constrictions were recorded. The magnitude of these responses was sensitive to both color and frequency parameters; red-blue color-paired flicker consistently produced the strongest constrictions. These responses occurred even when the flicker was of a lower luminance, both physically and perceptually, than a preceding nonflickering color, indicating that chromatic rather than luminance sensitive mechanisms are involved in this response. Interestingly, the color- and frequency-sensitivity of constriction parallels those of flickers which maximally stimulate photosensitive epileptic patients, raising the possibility that chromatic response may be a factor in photosensitivity. PMID- 11206289 TI - Neuronal pathways from group-I and -II muscle afferents innervating hindlimb muscles to motoneurons innervating trunk muscles in low-spinal cats. AB - Synaptic inputs to motoneurons innervating the back and abdominal muscles in the lumbar part of the body from low-threshold hindlimb muscle afferents were studied in unanesthetized low-spinal cats. At a stimulus intensity of 1.2-1.5x threshold (T), which was sufficient to activate only group-I afferents, the incidence of post-synaptic potentials (PSPs) was higher when stimulating proximal muscle nerves than when stimulating distal muscle nerves (e.g., 52% versus 22% for motoneurons innervating m. iliocostalis lumborum: Ilio MNs; 38% versus 18% for motoneurons innervating m. obliquus externus: OEA MNs). At 2-5 T, at which group II as well as group-I muscle afferents were presumably stimulated, the PSP incidence increased irrespective of nerves stimulated (e.g., 76% for Ilio MNs; 60% for OEA MNs). The minimal central latencies of EPSPs evoked at 1.2-1.5 T ranged 0.8-16.7 ms for Ilio motoneurons and 1.4 -14.2 ms for OEA motoneurons, indicating that the connection between back and abdominal motoneurons and low threshold afferents from the hindlimb muscle include a monosynaptic one. The latencies of IPSPs were longer and ranged 1.9-18.8 ms for Ilio motoneurons and 2.4-15.8 ms for OEA motoneurons. Input patterns from various hindlimb muscles varied among individual motoneurons, even though they were within the same motoneuron pool. Such synaptic organization seems to differ from that for the leg motoneuron pool. The overall projection pattern of low-threshold afferents from leg muscles to lumbar back and abdominal motoneurons nevertheless suggests that group-I afferent inputs are related to lateral and vertical movements, and that group-II afferent inputs control the stiffness of the trunk. PMID- 11206290 TI - Operant conditioning of rat H-reflex affects motoneuron axonal conduction velocity. AB - This study assessed the effects of operant conditioning of the H-reflex on motoneuron axonal conduction velocity in the rat. After measurement of the control H-reflex size, rats were either exposed for at least 40 days to the HRup or HRdown conditioning mode, in which reward occurred only if the soleus H-reflex was greater than (HRup mode) or less than (HRdown mode) a criterion or continued under the control condition (HRcon mode) in which the H-reflex was simply measured. We then measured axonal conduction velocity of triceps surae motor units of HRup, HRdown, and HRcon rats by stimulating the axon in the ventral root and recording from the tibial nerve. Conduction velocity was 8% less in successful HRdown rats than in HRcon rats (P=0.02). Conduction velocity in HRup rats and unsuccessful HRdown rats was not significantly different from that in HRcon rats. Since recording bypassed the intra-spinal portion of the motoneuron, the change was clearly in the axon. This decrease was similar to the 6% decrease previously found in successful HRdown monkeys. Unsuccessful HRdown rats and monkeys did not show this decrease. This result suggests that the mechanism of HRdown conditioning is similar in rats and monkeys and provides further support for the hypothesis that HRdown conditioning decreases motoneuron excitability by producing a positive shift in firing threshold. While traditional theories of learning emphasize synaptic plasticity, neuronal plasticity may also contribute to operantly conditioned behavioral changes. PMID- 11206291 TI - Operant conditioning of rat H-reflex: effects on mean latency and duration. AB - We are currently studying the mechanisms of operantly conditioned changes in the H-reflex in the rat. Primate data suggest that H-reflex decrease is due to a positive shift in motoneuron firing threshold and a small decrease in the monosynaptic excitatory postsynaptic potential (EPSP), and that increase might be due to change in group-I oligosynaptic (especially disynaptic) input. To further evaluate the possibility of conditioned change in oligosynaptic input, we compared the mean latency (i.e., the average latency of the entire H-reflex) and the duration of control (i.e., pre-conditioning) H-reflexes with those of H reflexes after up-conditioning or down-conditioning. Up-conditioning was associated with small, statistically significant increases in H-reflex mean latency [+0.11+/-0.05 (+/-SE) ms] and duration (+0.32+/-0.16 ms). The mean latency of the H-reflex increase (i.e., the part added to the H-reflex by up conditioning) was 0.28+/-0.14 (+/-SE) ms greater than that of the control H reflex. Down-conditioning had no significant effect on mean latency or duration. While these results indicate that operant conditioning does not greatly change H reflex mean latency or duration, the effects detected with up-conditioning are consistent with the hypothesis that decreased inhibition, or increased excitation, by homonymous and heteronymous group-I oligosynaptic input contributes to the H-reflex increase produced by up-conditioning. Several other mechanisms might also account for these small effects. PMID- 11206292 TI - What do the MMPI scales fundamentally measure? Some hypotheses. AB - I consider the question of whether all psychopathological behaviors can, on an evolutionary foundation, be considered as positive adaptations. I proposed that higher functions can be differentiated from their associated emotional modulations at simultaneous subjective, behavioral, and neural levels and that organizing analyses in this way will enable us to fill in our understanding of both the effects and relief of traumatic experiences. I then present each of the 8 clinical scales of the MMPI (Hathaway & McKinley, 1943) as a dimension of positive adaptation with simultaneous cognitive-emotional, operant-classical, and neocortical-limbic elements. A variety of life-experience paradigms are then offered to explain the factors that operate to increase MMPI scale elevations as well as countermeasures that can operate to reduce such elevations. Understanding all such behaviors as adaptive leads to a notable enhancement of empathy. PMID- 11206293 TI - An openness scale for the California Psychological Inventory. AB - We developed a 36-item scale to measure Openness, using items on the California Psychological Inventory (CPI; Gough, 1957, 1987, 1996), Form 434. Items were initially chosen on the basis of content validity. Five samples (N = 2,375) were used to establish reliability, validity, and norms; 4 samples consisted of university undergraduate students, and 1 comprised applicants for nonmanagement call centerjobs. Internal consistency estimates obtained in each sample averaged approximately .75, and test-retest stability, assessed in 1 sample, was estimated at .84. Cross-correlations with related scales, for example, the NEO Personality Inventory-Revised Openness scale (Costa & McCrae, 1992) and other CPI-based scales, provided evidence of construct validity. Statistically significant predictive validities were obtained in 2 call centerjob-incumbent samples, with range-corrected true validities of .20 to .36 for a number of job performance criteria. Construct and predictive validity were found to be higher than for other scales consisting of CPI items designed to measure Openness or a related construct. Finally, norms were prepared for university undergraduate students (n = 1,847) and nonmanagement service-sector job applicants (n = 528). PMID- 11206294 TI - Should human figure drawings be admitted into court? AB - In recent years, there has been debate about the validity of figure drawings, although surveys of clinicians in both general and forensic practice still find them to be one of the most widely used tests of personality functioning. Using both Heilbrun's (1992) guidelines for the use of psychological tests in a forensic evaluation and the U.S. Supreme Court's Daubert v. Merrell Dow Pharmaceuticals, Inc. (1993) criteria for the admission of scientific evidence, I examine the admissibility of human figure drawings in court. The results suggest that the most commonly used methods for interpreting human figure drawings fall short of meeting the standards for admissibility. The use of overall rating scales, although weak in validity, appear to minimally meet these standards. PMID- 11206295 TI - Predicting DMS-IV cluster B personality disorder criteria from MMPI-2 and Rorschach data: a test of incremental validity. AB - Despite their frequent conjoint clinical use, the incremental validity of Rorschach (Rorschach, 1921/1942) and MMPI (Hathaway & McKinley, 1943) data has not been adequately established, nor has any study to date explored the incremental validity of these tests for predicting Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV]; American Psychiatric Association, 1994) personality disorders (PDs). In a reanalysis of existing data, we used select Rorschach variables and the MMPI PD scales to predict DSM-IV antisocial, borderline, histrionic, and narcissistic PD criteria in a sample of treatment seeking outpatients. The correlational findings revealed alimited relation between Rorschach and MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) variables, with only 5 of 30 correlations reaching significance (p <.05). Hierarchical regression analyses showed that both the MMPI and Rorschach data add incrementally in the prediction of DSM-IV borderline and narcissistic PD total criteria scores. The findings were less clear for the incremental value of Rorschach and MMPI-2 data in predicting the total number of DSM-IV histrionic PD criteria, which were best predicted by Rorschach data, and antisocial PD criteria, which were best predicted by MMPI-2 data. In addition to providing evidence of the incremental validity of Rorschach data, these findings also shed light on the psychological characteristics of the DSM-IV Cluster B PDs. PMID- 11206296 TI - Dimensions of self-serving misrepresentation in forensic assessment. AB - I conducted an exploratory principal components analysis of 15 scales that evaluate a variety of possible self-serving biases using assessment data from 101 general forensic clients. Three distinct factors emerged, representing exaggeration of psychiatric symptoms versus exaggeration of personal adjustment, exaggeration of virtue, and exaggeration of physical health difficulties. Confirmatory factor analysis supported the findings. The surprising fact that none of the scales contained a significant number of items representing the affirmation or exaggeration of positive mental health adjustment precluded the possibility of finding a specific factor in that area. The factor structure was similar to previous results based on personal injury evaluations alone, suggesting that this 3-factor categorization of self-serving misrepresentation has some degree of generality, at least in forensic settings. PMID- 11206297 TI - Psychological assessment on internship: a survey of training directors and their expectations for students. AB - We used a survey of internship training directors to examine the nature of assessment use and assessment skills training at 382 internship settings in professional psychology across the United States and Canada. For the purposes of this study, we created a questionnaire that inquired about the types of assessment instruments used at each internship setting, the amount and type of training offered at internship sites, and the type of assessment experience desired of interns before beginning their rotations. The results revealed several differences across type of internship facility surveyed as well as several trends in the current use of assessment in applied settings. The findings further demonstrate the important role of projective assessment in the training of graduate students and lead to the conclusion that major discrepancies may exist between what is being taught in graduate school and what students are expected to know on entering their internship positions. PMID- 11206298 TI - Agency and communion in the structure of parental representations. AB - We administered the revised Assessment of Qualitative and Structural Dimensions of Object Representations (Blatt, Chevron, Quinlan, Schaffer, & Wein, 1992) to 279 male and female undergraduate students and carried out independent principal components analyses of maternal and paternal ratings. Three stable factors, Agency, Communion, and Structure, were found in both sets of ratings. This factor structure differed from that reported by Quinlan, Blatt, Chevron, and Wein (1992). Results found here are consistent with contemporary interpersonal personality theory. PMID- 11206299 TI - Levels of interpersonal concerns and social functioning in early adolescent boys and girls. AB - Previous research has shown that the Interpersonal Concerns factor of the Depressive Experiences Questionnaire (DEQ; Blatt, D'Affliti, & Quinlan, 1976, 1979; Depressive Experiences Questionnaire for Adolescent [DEQ-A]; Blatt, Schaffer, Bers, & Quinlan, 1992) assesses 2 levels of interpersonal relatedness in young adults and older adolescents: neediness and relatedness. However, studies investigating the relation of the DEQ and DEQ-A with social functioning have not used the Neediness and Relatedness subscales of the Interpersonal Concerns factor. This study investigated (a) whether the Neediness and Relatedness subscales can be differentiated in a sample of early adolescents and (b) how the 2 subscales are differentially associated with indexes of social functioning. Results indicate that this differentiation of Neediness and Relatedness, and their associations with social functioning, emerges in early adolescence, especially for girls. PMID- 11206300 TI - Superiority of form% over Lambda for research on the Rorschach Comprehensive System. AB - Lambda is an important variable in the Rorschach Comprehensive System. However, because of the way it is calculated it has properties that can produce problems for parametric statistical analyses. We illustrate these difficulties and encourage the use of Form% (i.e., pure form responses/total responses) instead of Lambda in research. Form% is easy to calculate, and it is conceptually and mathematically comparable to Lambda. Because it is much more normally distributed, Form% is suitable to use in parametric analyses (e.g., t tests, analyses of variance, correlations, factor analyses, multiple regressions). PMID- 11206301 TI - Evaluation of an MMPI--a short form: implications for adaptive testing. AB - Efforts to develop a viable short form of the MMPI (Hathaway & McKinley, 1943) span more than 50 years, with more recent attempts to significantly shorten the item pool focused on the use of adaptive computerized test administration. In this article, we report some psychometric properties of an MMPI-Adolescent version (MMPI-A; Butcher et al., 1992) short form based on administration of the first 150 items of this test instrument. We report results for both the MMPI-A normative sample of 1,620 adolescents and a clinical sample of 565 adolescents in a variety of treatment settings. We summarize results for the MMPI-A basic scales in terms of Pearson product-moment correlations generated between full administration and short-form administration formats and mean Tscore elevations for the basic scales generated by each approach. In this investigation, we also examined single-scale and 2-point congruences found for the MMPI-A basic clinical scales as derived from standard and short-form administrations. We present the relative strengths and weaknesses of the MMPI-A short form and discuss the findings in terms of implications for attempts to shorten the item pool through the use of computerized adaptive assessment approaches. PMID- 11206302 TI - Body-esteem scale for adolescents and adults. AB - Body esteem (BE) refers to self-evaluations of one's body or appearance. This article outlines a BE questionnaire for adolescents and adults that has 3 subscales: BE-Appearance (general feelings about appearance), BE-Weight (weight satisfaction), and BE-Attribution (evaluations attributed to others about one's body and appearance). The subscales have high internal consistency and 3-month test-retest reliability. Females scored lower than males on BE-Weight and BE Appearance. BE-Weight was the only subscale uniquely related to weight, especially in females, with heavy individuals tending to be dissatisfied with their weight. BE-Appearance was the only subscale that consistently predicted self-esteem. BE-Appearance and BE-Weight covaried more with Neeman and Harter's (1986) Appearance subscale than with other self-esteem subscales; BE-Attribution covaried more with social self-esteem subscales than did BE-Appearance and BE Weight. PMID- 11206303 TI - Working towards a real cure for patients with small hepatocellular carcinoma. PMID- 11206304 TI - Comparison of intraductal ultrasonography with percutaneous transhepatic cholangioscopy for the identification of residual bile duct stones during lithotripsy. AB - BACKGROUND: An imaging modality that can be used to identity small stones after a biliary lithotripsy is required. Intraductal ultrasonography was evaluated by using percutaneous transhepatic cholangioscopy as the gold standard. METHODS: Lithotripsy, under percutaneous transhepatic cholangioscopy guidance, was performed in 20 patients. A thin-caliber ultrasonic probe (2.0 mm in diameter and 20 MHz frequency) was inserted into the bile duct through the percutaneous tract after lithotripsy, and residual stones were identified. This was followed by percutaneous transhepatic cholangioscopy. RESULTS: In the extrahepatic bile ducts, intraductal ultrasonography provided images of all the stones demonstrated on cholangioscopy (n = 11). The sensitivity was superior to that of cholangiography (P < 0.005). However, in the intrahepatic bile ducts, intraductal ultrasonography only visualized the stones located in the cannulated lobe. Extrahepatic stones smaller than 5.0 mm in diameter or in a common hepatic duct larger than 15.0 mm in diameter were missed by cholangiography, but were visualized by the use of intraductal ultrasonography (P < 0.05). CONCLUSIONS: Intraductal ultrasonography is equivalent to cholangioscopy in the extrahepatic bile ducts. Cholangiography and intraductal ultrasonography should be used in combination to image intrahepatic and extrahepatic stones. PMID- 11206305 TI - Images of interest. Gastrointestinal: gallstone ileus. PMID- 11206306 TI - Images of interest. Hepatobiliary and pancreatic: a woman with abdominal pain and fever. PMID- 11206307 TI - Acinar cell carcinoma with hypervascularity. AB - Acinar cell carcinoma is an uncommon malignancy with a reported incidence of 1% among exocrine tumors of the pancreas. The case of a 60-year-old Taiwanese man who presented with obstructive jaundice, abdominal pain, and body weight loss is described here. A mixed clinical picture of islet cell tumor and ductal carcinoma of the pancreas was shown to be a hypervascular tumor at the pancreatic head region with an irregular stricture at the common channel of the common bile and pancreatic ducts. The patient had normal levels of plasma carcinoembryonic antigen, carbohydrate antigen 19-9, alpha-fetoprotein, but an increase in plasma levels of insulin and C-peptide. Immunohistochemical stains and electron microscopic examination of the tumor was consistent with acinar cell carcinoma. PMID- 11206308 TI - Lupus-like syndrome with submassive hepatic necrosis associated with hepatitis A. AB - Hepatitis A is a common self-limited liver disease. However, 15% of patients may have some complications. Autoimmune hepatitis that is triggered by viral hepatitis has been reported. We hereby describe an unrecognized association of hepatitis A with a full blown lupus-like syndrome manifested by the appearance of arthralgia, exudative pleural effusion with the presence of lupus erythematosus cells and autoantibodies. All these findings disappeared after a short course of steroid treatment. The case is presented and the literature is reviewed. PMID- 11206309 TI - Acute hepatitis induced by Shou-Wu-Pian, a herbal product derived from Polygonum multiflorum. AB - Herbal preparations are widely available and generally regarded by the public as harmless remedies for a variety of medical ailments. We report the first case in Australia of acute hepatitis associated with the Chinese herbal medicine Shou-Wu Pian, prepared from Polygonum multiflorum. Cholestatic hepatitis developed in a Chinese woman taking this preparation for the greying of her hair, and liver biopsy was consistent with a toxic reaction. Clinical and biochemical resolution occurred following cessation of the drug. PMID- 11206310 TI - Aging increases, and duodenal ulcer reduces the risk for intestinal metaplasia of the gastric corpus in Japanese patients with dyspepsia. AB - BACKGROUND AND AIMS: The classification of gastritis by using the revised Sydney system suggests that there are two types of Helicobacter pylori-related gastritis. The aim of the present study was to examine the risk factors that might be involved in the presence of either atrophic gastritis or intestinal metaplasia of the gastric corpus of Japanese patients. METHODS: Biopsy samples were obtained from the gastric corpus in 154 patients with dyspepsia, and the degree of atrophy or intestinal metaplasia was determined histologically. The correlation between several variables and presence of atrophy or intestinal metaplasia was evaluated by using multivariate analysis. RESULTS: Among the 11 variables, which included age, peptic ulcer diseases and H. pylori infection, H. pylori infection was the major risk factor associated with the presence of atrophic gastritis or intestinal metaplasia of the gastric corpus. In contrast, duodenal ulcer (DU) disease reduced the risk of contracting both conditions. Age was an independent risk factor only for intestinal metaplasia of the gastric corpus. When 128 H. pylori-positive subjects were analyzed, DU and age were similarly associated with the presence of both conditions. CONCLUSIONS: These results suggest that DU reduces the risk for contracting atrophic gastritis and intestinal metaplasia, and age is an independent risk factor for intestinal metaplasia of the gastric corpus in dyspeptic Japanese patients. PMID- 11206311 TI - Molecular therapy with recombinant antisense c-myc adenovirus for human gastric carcinoma cells in vitro and in vivo. AB - BACKGROUND AND AIMS: This study used a recombinant antisense c-myc adenovirus (Ad ASc-myc) to evaluate how alterations of c-myc expression in the SGC7901 human gastric carcinoma cells could influence the proliferation, apoptosis and the growth of human gastric tumors in nude mice. METHODS: The human gastric carcinoma cell line, SGC7901, treated with Ad-ASc-myc or adenovirus recombinants carrying LacZ gene (Ad-LacZ) were analyzed by using X-gal stain, MTT, DNA ladder, TUNEL assay, flow cytometric analysis, polymerase chain reaction and western blot in vitro. The tumorigenicity and experimental therapy in nude mice models were assessed in vivo. RESULTS: The Ad-ASc-myc could strongly inhibit cell growth and induce apoptosis in SGC7901 cells. The proliferation of the Ad-ASc-myc-infected SGC7901 cells was reduced by 44.1%. The mechanism of killing gastric carcinoma cells by Ad-ASc-myc was found to be apoptosis, which was detected by the use of a DNA ladder, TUNEL and flow cytometric analysis. Infection of Ad-ASc-myc in nude mice showed that all three mice failed to form tumors from the 7 to 30 day period, compared with injection of Ad-LacZ and parent SGC7901 cells. Experimental therapy on the nude mice bearing subcutaneous tumors of SGC7901 cells showed that intratumor instillation of Ad-ASc-myc inhibited the growth of the tumors. Recombinant antisense c-myc adenovirus-treated tumors were inhibited by 68.9%, compared with tumors injected with Ad-LacZ and control (LacZ and phosphate buffered saline). CONCLUSION: The expression of Ad-ASc-myc can inhibit growth and induce apoptosis of gastric cancer cells in vitro and in vivo and thus is a potential clinical utility in gene therapy for the treatment of gastric carcinoma. PMID- 11206312 TI - Kinetics of the hepatitis C virus during interferon therapy as a marker of therapeutic response. AB - BACKGROUND: The viral load and subtype of hepatitis C virus (HCV) are predictors of the efficacy of interferon (IFN) therapy. The kinetics of HCV during IFN therapy have been described recently, suggesting that HCV infection is highly dynamic. These observations have raised the issue as to whether early monitoring of the viral load can help guide IFN therapy. METHODS: We measured HCV-RNA levels at 0, 24 and 48 h after the start of IFN-alpha treatment (10 MU daily for 2 weeks and then three times weekly for 22 weeks) or IFN-beta treatment (6 MU daily for 6 weeks). Then we analyzed the relationship between HCV kinetics and therapeutic response using stepwise multivariate logistic regression analysis. RESULTS: The exponential decay slope of the viral load during the first 24 h, not the first 48 h or the next 24 h, was a predictor of viral eradication at 6 months after completion of the treatment (sustained response; P = 0.0023). This decay slope was not affected by the HCV serotype or the type of IFN used. Initial viral load and HCV serotype were also predictors, as reported previously (P < 0.0001 and P = 0.0347, respectively). We also proposed a model using a prognostic index that predicted a sustained response with more than 80% sensitivity, specificity and efficacy in an independent and external group of patients. CONCLUSION: This study demonstrated that the exponential decay slope of the viral load during the first 24 h was an important predictor of the response to IFN therapy as well as the initial viral load and HCV serotype. The model may also be useful for the clinical management of IFN therapy. PMID- 11206313 TI - Use of ursodeoxycholic acid in liver diseases. AB - Ursodeoxycholic acid is currently the only established drug for the treatment of chronic cholestatic liver diseases. It has cytoprotective, anti-apoptotic, membrane stabilizing, anti-oxidative and immunomodulatory effects. Prolonged administration of ursodeoxycholic acid in patients with primary biliary cirrhosis (PBC) is associated with survival benefit and a delaying of liver transplantation. There is evidence that it might even prevent progression of the histologic stage of PBC. It also has a beneficial effect on primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, liver disease associated with cystic fibrosis, chronic graft versus host disease, total parenteral nutrition associated cholestasis and various pediatric cholestatic liver diseases. In the present review the current knowledge about the mechanisms of the action and role of ursodeoxycholic acid in the treatment of various liver diseases has been discussed. PMID- 11206314 TI - Subcellular redistribution of protein kinase C isozymes is associated with rat liver cirrhotic changes induced by carbon tetrachloride or thioacetamide. AB - BACKGROUND AND AIMS: Protein kinase C (PKC) plays a key role in the alteration of signal transduction in the liver, which may contribute to the development of liver cirrhosis. The aim of the present study was to examine the subcellular redistribution of PKC isozymes in rat liver cirrhosis, which is induced by two different cirrhotic chemical agents, carbon tetrachloride (CCl4) and thioacetamide (TAA). METHODS AND RESULTS: Thioacetamide and CCl4 were administered to rats for 8 and 30 weeks, respectively before rats were killed and autopsies performed at 9, 20 and 30 weeks later. The TAA induced a fibrotic pattern in the liver that differed from that produced by CCl4, notably in the formation of fibrous connective tissue and the proliferation of bile ductule cells. Cholangiofibrosis and clear-cell foci were also observed in TAA-treated rats at 30 weeks. Histological examination revealed that severe cirrhotic changes were present 9 weeks after the commencement of CCl4 treatment and 30 weeks after TAA treatment. DISCUSSION: When the subcellular redistribution of PKC isozymes (PKCalpha, -beta1, -delta, and -epsilon) was examined, all the PKC isozymes in CCl4-treated rats were found to be translocated to the membrane fraction, which may mean PKC activation, and then downregulated by proteolytic degradation after 9 weeks of treatment, which coincided with peak cirrhotic changes. All rats treated with CCl4 recovered to the control level after 20 weeks of treatment. In the case of TAA-treated rats, PKC isozymes were translocated to the particulate fraction of the liver after 9 weeks of treatment and this persisted in most of the rats for the duration of the experiment. CONCLUSIONS: From these results, it would appear that PKC translocation preceded morphologic changes, and that an altered subcellular distribution of the PKC isozyme may be associated with the response to liver damage and carcinogenesis. PMID- 11206315 TI - Portal hypertensive response to bradykinin in inflamed or cirrhotic rat livers is mediated by B2-type receptors. AB - BACKGROUND: We have shown that the portal hypertensive response to bradykinin in normal rats is mediated by B2 receptors. METHODS: By using isolated and exsanguinated rat liver perfusion, we studied the portal hypertensive response to bradykinin or des-Arg9-bradykinin (B1 agonist) in inflamed or cirrhotic rat livers. Livers were perfused with bovine serum albumin Krebs-Henseleit buffer (pH 7.4; 37 degrees C) at a constant flow rate, in the absence or presence of des Arg9[Leu8]-bradykinin or HOE 140 (B1 and B2 receptor antagonists, respectively). Bradykinin (140 nmol) or des-Arg9-bradykinin was injected as a bolus via the afferent route to the liver. RESULTS: Basal perfusion pressure in liver-cirrhotic rats was higher than in normal rats. In normal, inflamed, or liver-cirrhotic rats, the presence of the B1 antagonist did not change the portal hypertensive response to bradykinin, while the B2 antagonist abolished this response. A 140 nmol dose of des-Arg9-bradykinin did not change the perfusion pressure; 700 nmol of this B1 agonist produced an insignificant perfusion pressure increase. The perfusion pressure increase induced by bradykinin in cirrhotic livers was lower than in normal livers. CONCLUSIONS: The portal hypertensive response to bradykinin in inflamed or cirrhotic rat livers is mediated by B2 receptors, but not B1 receptors, and there is a contracting hyporeactivity to bradykinin in cirrhotic rat livers. PMID- 11206316 TI - Importance of achieving complete necrosis during the first treatment for hepatocellular carcinoma to prevent bone metastasis: a prospective study. AB - BACKGROUND AND AIMS: Recent advances in the treatment of hepatocellular carcinoma (HCC) have changed the importance of bone metastasis during the follow up of such patients. In the present study, we investigated risk factors for bone metastasis after treatment for HCC. METHODS: Two hundred and two patients with HCC were diagnosed as free of bone metastasis by technecium 99m-methylene diphosphonate bone scintigraphy and were followed prospectively after treatment of the primary lesions (follow-up period 2-146 months; median 20 months). We statistically analyzed the risk factors for bone metastasis using the clinical characteristics at the time of first treatment. RESULTS: Multiple tumors (P < 0.005), main tumor size > 5 cm in diameter (P < 0.005), the presence of distant metastasis (P < 0.005), elevation of serum alpha-fetoprotein (> 100 ng/mL; P < 0.05), chemotherapy (P < 0.05) and insufficient therapeutic response (P < 0.0005) were identified as risk factors for bone metastasis by univariate analyses. Insufficient therapeutic response and main tumor size > 5 cm in diameter (both P < 0.05) were identified as independent predisposing factors for bone metastasis. CONCLUSIONS: Complete necrosis of primary HCC during the first treatment is important to prevent subsequent bone metastasis. PMID- 11206317 TI - Survival of conditionally immortalized hepatocytes in the spleen of syngeneic rats. AB - BACKGROUND: Hepatocyte transplantation has been shown to be effective in the treatment of liver failure; however, the shortage of donor organs limits its clinical application. Several reports have suggested that conditionally immortalized hepatocytes (CIH) could be an alternative to primary hepatocytes. However, CIH are known to undergo apoptosis in vitro at a non-permissive temperature, which is similar to body temperature. METHODS: To investigate the duration of survival and in vivo apoptosis of CIH in the syngeneic host, the L2A2 cells (a kind of CIH) that were established from hepatocytes of a Lewis rat with a gene for a temperature-sensitive Simian Virus 40 (SV40) large T antigen were transplanted into the spleen. Cells were isolated from the spleen that was removed periodically up to 6 months, and used to detect the presence of the L2A2 cells among them with the selective culture for CIH and T-antigen PCR. In situ apoptosis of L2A2 cells was also examined. In order to improve the survival of transplanted L2A2 cells in the host, a group of rats were partially hepatectomized 1 day before transplantation was performed. RESULTS: The L2A2 cells secreted albumin at a rate of 1.17 +/- 0.18 microg/24 h per 10(6) cells in vitro. After transplantation, L2A2 cell colonies and PCR amplification bands appeared up to 14 and 7 days, respectively, but this duration was not prolonged by a partial hepatectomy. The spleen showed a large number of hepatocytes that were in the process of dying on the 5th day, and only a number of ghost hepatocytes were present on the 7th day of transplantation. No tumors were found during the 6-month observation period. CONCLUSIONS: Conditionally immortalized hepatocytes can survive in the spleen for a limited period, in spite of the growth stimulation, most likely because they undergo apoptosis in vivo as well as in vitro at a non-permissive temperature. These data suggest that the use of these cells in hepatocyte transplantation be limited to temporary hepatic support. PMID- 11206318 TI - Endotoxin treatment causes an upregulation of the endothelin system in the liver: amelioration of increased portal resistance by endothelin receptor antagonism. AB - BACKGROUND: Mechanisms underlying hepatic microcirculatory failure during endotoxemia are incompletely understood. Because endothelin-1 (ET-1) has been implicated in endotoxin-induced liver injury, we investigated the hepatic ET-1 system in endotoxin-treated rats. METHODS: Rats were treated with endotoxin (Escherichia coli lipopolysaccharide; 3 mg/kg, i.p.), and various determinations were made 24 h later. RESULTS: Endotoxin treatment caused 11.2 +/- 1.6% weight loss, a decrease in mean arterial pressure (MAP; 96 +/- 5 mmHg vs 108 +/- 3 mmHg; P < 0.05) and an increase in portal pressure (11.6 +/- 1.3 mmHg vs 7.4 +/- 1 mmHg; P < 0.02). No significant changes in the serum levels of liver enzymes or hepatocellular necrosis were observed. Endotoxin caused increases in hepatic ET-1 (from 345 +/- 31 to 565 +/- 38 pg/g; P < 0.01), ET-1 receptor density (from 179 +/- 16 to 340 +/- 26 fmol/mg; P < 0.02), and mRNA expression of preproendothelin 1, and ET(A) and ET(B) receptors. While the serum nitric oxide (nitrite +/- nitrate) concentration was increased in endotoxin-treated rats, that of ET-1 remained unchanged. A mixed ET(A)/ET(B) receptor antagonist, TAK-044 (10 mg/kg, i.v.), reduced the weight loss from 11.2 +/- 1.6% to 5.9 +/- 2.9% (P < 0.05) and the portal pressure from 11.6 +/- 1.3 mmHg to 8.6 +/- 0.7 mmHg (P < 0.05) in endotoxin-treated rats. The mixed ET(A)/ET(B) receptor antagonist also caused an increase in serum ET-1 concentration, but did not affect serum nitric oxide and MAP in endotoxin-treated rats. CONCLUSIONS: These results suggest that the upregulated hepatic ET-1 system is an important mechanism of increased portal resistance and related complications of endotoxemia. PMID- 11206319 TI - Aortic hyporeactivity to norepinephrine induced by lipopolysaccharide in cirrhotic rats: beneficial effects of a non-steroidal anti-inflammatory drug coupled with a nitric oxide donor. AB - BACKGROUND AND AIMS: Cirrhosis is associated with a hyperdynamic syndrome and arterial vasodilation that is related to nitric oxide (NO) synthase 3 overactivity. Septic shock is frequently associated with cirrhosis and with a vascular induction of NO synthase 2. The aims of this study were to compare the effects of lipopolysaccharide (LPS) in normal and cirrhotic rats, and to test the effects of a nonsteroidal anti-inflammatory drug (NSAID) coupled with a (NO) donor. METHODS: Cirrhotic rats received NO-flurbiprofen, flurbiprofen or vehicle followed by LPS or placebo 15 min later. The heart rate and mean arterial pressure of rats were monitered for 5 h. Thoracic aortic rings were removed and contracted with the use of norepinephrine. Nitric oxide synthase activity was measured in the aorta and stomach of cirrhotic rats. RESULTS: Arterial pressure decreased in cirrhotic rats in the vehicle/LPS and flurbiprofen/LPS groups. After LPS administration, the heart rate of rats increased in all groups. In the aortic rings, LPS induced hyporeactivity to norepinephrine in all groups except the NO flurbiprofen group. This hyporeactivity was abolished after preincubation with Nw nitro-L-arginine (L-NNA). Nw-nitro-L-arginine had no effect on norepinephrine induced vasoconstriction in the NO-flurbiprofen/LPS group. Nitric oxide synthase 2 activity in the stomach and aorta of cirrhotic rats was increased in each group except in the NO-flurbiprofen group after LPS administration. Pretreatment with NO NSAID prevented aortic hyporeactivity to norepinephrine in cirrhotic rats treated with LPS as it probably inhibited the NO synthase 2 induction. CONCLUSIONS: These findings suggest that NO-flurbiprofen has a beneficial hemodynamic effect in cirrhotic rats and may help to prevent LPS aortic hyporeactivity. PMID- 11206320 TI - Pancreatitis-associated protein-I mRNA expression in mouse pancreas is upregulated by lipopolysaccharide independent of cerulein-pancreatitis. AB - BACKGROUND AND AIMS: It is well known that endotoxemia, which is caused by a bacterial infection, can exacerbate acute pancreatitis, whereas pancreatitis associated protein (PAP) has the ability to induce bacterial aggregation. Pancreatitis-associated protein is supposed to protect the tissue from infection during inflammation. In order to clarify the relationship between PAP mRNA expression and endotoxemia during acute pancreatitis, the kinetic patterns of PAP I mRNA in mouse pancreas treated with either cerulein or lipopolysaccharide (LPS) or both were investigated in this study. METHODS AND RESULTS: The administration of LPS (5 mg/kg) intraperitoneally resulted in a dramatic upregulation of PAP-I mRNA expression, increasing 18.61-fold to a maximum at 12 h, then decreasing, but still sustaining at a high level and reaching baseline on day five. These changes were accompanied by the upregulation of tumor necrosis factor (TNF)-alpha, interleukin-1beta (IL-1beta), interleukin 6 (IL-6) and interferon gamma (IFNgamma) mRNA expressions in the pancreas, but not by marked alterations of serum amylase, lactic dehydrogenase (LDH) and histology. Cerulein also increased PAP-I mRNA expression. However, the combination of cerulein and LPS was not able to enhance PAP-I mRNA expression further, although more prominent pancreatitis based on significant changes of serum amylase, LDH and histology were observed. CONCLUSION: These results suggest that PAP-I mRNA might be modulated by endotoxemia, independent of cerulein-pancreatitis. There were no strong correlations between PAP-I mRNA expression and the severity of pancreatitis. PMID- 11206321 TI - Evaluation of pancreatic secretion after administration of secretin: application of magnetic resonance imaging. AB - BACKGROUND: To evaluate pancreatic exocrine function, we measured the changes in T2 enhanced hydrograhic intensity on magnetic resonance (MR) images of the pancreas following an injection of secretin, which is representative of the changes in duodenal fluid volume. METHODS: The subjects were 10 patients with normal pancreatic function (N > 70% detected by using a pancreatic function diagnostant test) and 12 patients with hypo-function, including those with mild hypo-function (MH, 50-70%, six patients) and severe hypo-function (SH < 50%, six patients). RESULTS: In the N group, T2 enhanced intensity of the pancreas increased to a maximum value (more than 10% compared with baseline) within 5 min of stimulation, then gradually decreased. No significant difference in the response was observed between the head and body of the pancreas. Changes in the MH group were similar to those of the N group. In contrast, significantly lower changes in T2 enhanced intensity were observed in SH group, relative to both the N and MH group (P < 0.05). The amount of secretin-induced increase in duodenal fluid after 16 min was not significantly different among the three groups. Furthermore, an evaluation of the residual pancreatic tissue after a pancreatoduodenectomy was also feasible. CONCLUSIONS: Our results indicate that the MR-secretin test is useful for the evaluation of severe pancreatic exocrine dysfunction. The diagnostic test is simple, direct and non-invasive. PMID- 11206323 TI - Dictyostelium discoideum: a model system for differentiation and patterning. AB - In Dictyostelium, development begins with the aggregation of free living amoebae, which soon become organized into a relatively simple organism with a few different cell types. Coordinated cell type differentiation and morphogenesis lead to a final fruiting body that allows the dispersal of spores. The study of these processes is having increasing impact on our understanding of general developmental mechanisms. The availability of biochemical and molecular genetics techniques has allowed the discovery of complex signaling networks which are essential for Dictyostelium development and are also conserved in other organisms. The levels of cAMP (both intracellular and extracellular) play essential roles in every stage of Dictyostelium development, regulating many different signal transduction pathways. Two-component systems, involving histidine kinases and response regulators, have been found to regulate intracellular cAMP levels and PKA during terminal differentiation. The sequence of the Dictyostelium genome is expected to be completed in less than two years. Nevertheless, the available sequences that are already being released, together with the results of expressed sequence tags (ESTs), are providing invaluable tools to identify new and interesting genes for further functional analysis. Global expression studies, using DNA microarrays in synchronous development to study temporal changes in gene expression, are presently being developed. In the near future, the application of this type of technology to the complete set of Dictyostelium genes (approximately 10,000) will facilitate the discovery of the effects of mutation of components of the signaling networks that regulate Dictyostelium development on changes in gene expression. PMID- 11206322 TI - Long-term evaluation of extracorporeal shock-wave lithotripsy for cholesterol gallstones. AB - BACKGROUND: Extracorporeal shock-wave lithotripsy (ESWL) is a treatment that preserves the gallbladder. Problems after ESWL treatment include stone recurrence and the development of biliary symptoms. METHODS: Two hundred and sixty-two patients with cholesterol-type gallstones, the best indication for ESWL treatment, and 42 control patients with cholesterol-type gallstones who received no treatment entered this study. We evaluated the factors associated with recurrence of gallstones after stone clearance and the development of biliary symptoms after ESWL treatment. RESULTS: The 3-, 5- and 7-year cumulative probabilities of gallstone recurrence were 20.6, 27.1 and 33.1%, respectively, with the recurrence probability significantly lower in patients with good gallbladder contractility. In patients with recurrence, ursodeoxycholic acid (UDCA) treatment was effective. In 69 patients with residual gallstones, the 3-, 5- and 7-year cumulative risks of biliary symptoms were 17.3, 24.9 and 30.5%, respectively. With residual gallstones, the risk of biliary symptoms developing was significantly lower in patients with a < or = 3 mm fragment size at the end of ESWL treatment and in those treated consistently with UDCA for 6 months or more after treatment with ESWL. The risk of biliary symptoms was significantly lower in ESWL-treated patients with residual stones who had a < or = 3 mm fragment size after treatment compared to those of control patients. CONCLUSIONS: Ursodeoxycholic acid was effective in clearing stones in patients with gallstone recurrence. In patients with residual stones, the fragmentation of stones to < or = 3 mm and UDCA administration effectively reduced the risk of subsequent biliary symptoms. PMID- 11206324 TI - Fertilization triggers activation of Fyn kinase in the zebrafish egg. AB - Fertilization results in the tyrosine phosphorylation of several egg proteins and studies have shown that tyrosine protein kinase activity is required for successful fertilization. The Fyn protein kinase has been detected in eggs of the sea urchin, frog and rat, although measurement of fertilization-induced changes in Fyn kinase activity have only been successful in the sea urchin system. The present study demonstrates the presence of Fyn kinase in the zebrafish egg and the stimulation of this enzyme at fertilization. Activation of Fyn was detected as early as 30 seconds post-fertilization and increased approximately six-fold by 2 minutes post-insemination. The activation of Fyn in the zebrafish egg required sperm and was not observed in spontaneously activated eggs. PMID- 11206325 TI - Controlled translation initiation on insulin-like growth factor 2-leader 1 during Xenopus laevis embryogenesis. AB - A number of growth factors, whose spatio-temporal expression is essential for embryonic development, are encoded by mRNAs with a complex 5'UTR. Human insulin like growth factor 2 mRNA contains a long (592 nucleotides) 5'UTR (IGFl1) with one upstream open reading frame and stable stem-loop structures, elements which might be important for controlled translation. To investigate whether these unusual features of IGFl1 can control translation initiation during embryogenesis, we examined the initiation efficiency on this 5'UTR during development of Xenopus laevis. The results demonstrate that IGFl1 strongly represses translation of a reporter in early embryos, compared with the Xenopus beta-globin 5'UTR. The inhibition is alleviated soon after the midblastula transition, suggesting a stimulatory effect of the transcription start. However, a similar stimulation of IGFl1-driven translation is seen in embryos in which de novo transcription was inhibited by actinomycin D. Furthermore, it is shown that up-regulation of IGFl1 activity is independent of eIF4E levels, and activity of IGFl1 is observed in all tissues of transgenic Xenopus embryos. These results indicate that post-translational modulation of a trans-acting factor enables efficient initiation on this complex 5'UTR after the midblastula transition. PMID- 11206326 TI - Sequence and translation initiation properties of the xenopus TGFbeta5, PDGF-A, and PDGF-alpha receptor 5' untranslated regions. AB - The properties of the architecturally complex Xenopus laevis TGFbeta5, PDGF-A and PDGF-alpha receptor 5'UTRs were investigated. 5' extended cDNAs were obtained by 5'RACE, resulting in long 5'UTRs (478-710 nt) with multiple upstream AUGs (3-13), andthe potential to fold into stable structures. Injection studies suggested that the cloned PDGF-alphaR 5'UTR contains an intron. Splicing at potential 5' and 3' splice sites would result in a non-complex 5'UTR of 142 nt. The above mentioned 5'UTR characteristics are inhibitory for ribosomal scanning. Indeed, relative to the beta-globin 5'UTR, the complex 5'UTRs strongly repressed initiation of protein synthesis in pre-MBT Xenopus embryos. However, later in embryogenesis, the inhibition was partly relieved. The results show temporal translational control by these 5'UTRs. Transgenic embryos showed that the 5'UTRs allowed translation throughout the embryo; spatial control could not be observed. Interestingly, a fragment in the PDGF-A 5'UTR highly similar to an element in the human PDGF-A 5'UTR is complementary to Xenopus 18S ribosomal RNA. None of these Xenopus 5'UTRs contains an IRES, as determined by injecting bicistronic constructs. PMID- 11206327 TI - Morphological chimeras of larvae and adults in a hydrozoan--insights into the control of pattern formation and morphogenesis. AB - In the marine hydroid Hydractinia echinata, metamorphosis transforms the spindle shaped larva into a primary polyp. It bears a hypostome with a ring of tentacles at its apical end, a gastric region in the middle and stolons at the base. In nature, metamorphosis is induced in response to external stimuli provided by bacteria. These stimuli can be replaced by artificial inducers, one of which is heat shock. Among heat shock treated stages are those undergoing complete metamorphosis but also specimens forming chimeras of different developmental stages. In the chimeric larvae, the posterior is transformed into the apical hypostome of the adult polyp while the anterior part of the larva persists as larval tissue. After transverse sectioning, these stage chimeras regenerate the missing body parts with respect to the nature of the tissue at the wound surface. This shows that the decision to make larva or polyp morphology depends not on the majority of the tissue in the original body section, but on stage specificity within the regenerating animal part. Single cells can escape from this general rule, since RFamide nerve cells which usually differentiate in polyp tissue appear in regenerated larval tails of sectioned stage chimeras. The results indicate that the pattern-forming system of the larva and of the adult have features in common. The primary signals controlling patterning along the anterior posterior axis in larvae and the apical-basal axis in polyps arethus likelyto be the same while the interpretation of these primary signals by the individual cells changes during metamorphosis. PMID- 11206328 TI - Patterns of migration and regulation of trunk neural crest cells in zebrafish (Danio rerio). AB - Regulation is the replacement of lost, undifferentiated embryonic cells by neighboring cells in response to environmental signals. Neural crest cells, embryonic cells unique to craniates, are good candidates for studies of regulation because they are pluripotent, and thus might be able to alter their behavior in response to environmental signals. This study investigated regulation for the loss of trunk neural crest (TNC) cells, specifically pigment derivatives, in the zebrafish, Danio rerio. The first part of the study clarifies and extends what has previously been described on normal patterns of TNC migration and differentiation. These data were then used to address the hypothesis that there is regulation for loss of TNC, and that regulation would vary with the amount removed, the position or stage of removal. Zebrafish TNC cells are large and numerous. SEM and Dil labeling revealed that TNC cells undergo several successive waves of 'sheet' and 'segmental' migration, beginning as early as the 12 somite stage. Dil-labeled TNC cells often migrated several somite lengths anteriorly and posteriorly along the trunk axis to form glial cells, ganglia, pigment, ectomesenchyme and tail reticular cells. Regulation occurred on a sliding scale, ranging from complete to incomplete. Defects in development and/or pigmentation occurred if large regions of TNC cells were removed, or if cells were removed from anterior (cardiac) and posterior (tail) extremities of the trunk. Melanophores were the cell type most visibly affected by TNC extirpations. Otherwise, pigmentation was remarkably normal. We propose that the completeness of regulation largely depends upon healing of the overlying epidermis. PMID- 11206329 TI - Tissue-specific distribution and variation of the channel-forming protein ductin during development of Drosophila melanogaster. AB - Ductins represent membrane channel proteins which are supposed to form both proton channels in V-ATPases and connexon channels in gap junctions. In order to localize and characterize these proteins in different tissues of Drosophila, we applied indirect immunofluorescence microscopy and immunoblots, using antisera prepared against Drosophila ductin and against Nephrops ductin. Previously, these antisera have been shown to recognize, in ovarian follicles and young embryos of Drosophila, the ductin monomer of 16 kDa and a putative dimer of 29 kDa. Moreover, both anti-ductin sera label antigens in plasma membranes and in the cytoplasm and block, when microinjected, cell-cell communication via gap junctions. In the present study, comparing several embryonic, larval and adult tissues, the anti-ductin sera were found to recognize antigens with various locations in cells of the midgut, the salivary gland, the nervous system, the muscles and the epidermis. For example, in midgut cells, antigens were labeled mainly in apical plasma membranes and in the apical part of the cytoplasm, while in salivary-gland cells, labeling was found throughout the plasma membranes and the cytoplasm. We conclude that putative gap junctions were revealed in the salivary gland, the nervous system and the epidermis, while plasma membrane associated putative V-ATPases were detected in the midgut, the salivary gland and the muscles. Moreover, V-ATPases associated with cytoplasmic vesicles were found in almost every tissue. On immunoblots of homogenates from various tissues, the anti-ductin sera specifically labeled bands of 16, 21 and 29 kDa. When comparing these bands using peptide mapping with V8 protease, we found that they represent closely related proteins. Therefore, either different ductins or modifications of a single ductin appear to be present in different cellular regions, cell types and developmental stages of Drosophila. PMID- 11206330 TI - Time-lapse observation of branching morphogenesis of the lung bud epithelium in mesenchyme-free culture and its relationship with the localization of actin filaments. AB - It has been shown that branching morphogenesis of the lung bud is mediated by epithelial-mesenchymal interaction via such molecules as FGF10, BMP4 and Shh. However, a recent study showed that the isolated lung epithelium still undergoes branching morphogenesis in vitro even in the absence of mesenchyme (Nogawa and Ito, 1995). In the present study, we observed in vitro the dynamic movement of the isolated lung epithelium of the fetal mouse using time-lapse recording, and investigatedthe roles of actinfilaments in branching of the lung bud. First, time lapse observation of the initial phase of lung branching morphogenesis revealed that at the sites of cleft formation, the epithelial surface was retracted inward from its original position. From this observation we assumed that there should be some structures which exert a physical force on the epithelium, and the localization and arrangement of actin fibers in the cultured lung epithelium were examined at various stages of branching morphogenesis. At the prebudding (6 h) and onset-budding (24 h) stages, no specific localization of actin filaments was observed in the lung bud epithelium, but at the postbudding stage (48 h) they were localized densely in the cells at the tip of the branched lung epithelium. The cell density was not different between the tip and cleft regions of the lung bud epithelium. When cultured with FGF-soaked beads, an actin-rich region was induced at the tip of the lung bud which was growing toward an FGF-soaked bead. These results indicate that actin fibers do not play a significant part in cleft formation but can be secondarily induced by FGF in the surrounding matrix and play some roles at later shaping of the branch in lung morphogenesis. PMID- 11206331 TI - Cell morphology in amphioxus nerve cord may reflect the time course of cell differentiation. AB - Amphioxus embryos elongate following neurulation, and this lengthens the developing nerve cord. Most neurons and support cells remain attached at their apices to the neuroepithelium, and the apices themselves become correspondingly longer. In consequence, apex length can be used in some instances as a measure of whether a given cell last divided before elongation or after, and approximately when. The data indicate that most floorplate, ependymoglial and infundibular cells are generated comparatively early, before most neurons. Among the neurons, the segmentally arranged DC (dorsal compartment) motoneurons appear to be among the first to develop, which accords with molecular data on the time course of neural development, using neurogenin and islet as markers. PMID- 11206332 TI - Ambient atmospheric particles in the airways of human lungs. AB - Epidemiologic studies linking particulate matter (PM) air pollution and adverse respiratory and cardiovascular effects have focused attention on the interactions of PM and lung cells. Information on the types, numbers, composition, sizes, and distribution of ambient particles in the airways is potentially useful for correlations with pathological and/or physiological changes, but relatively little is known about the extent to which ambient particles actually enter airway epithelial cells and are retained in airway walls and even less information is available about correlations with pathologic changes. Since many ambient particles are colorless and/or well below the level of resolution of light microscopy, definitive evaluation of particle burden in the airway wall requires analytical electron microscopy. Studies from the authors' laboratory suggest that in Vancouver, a city with relatively low PM levels, particle loads in the airway mucosa are nonetheless numerically substantial, typically in the range of 10(7) particles/g dry tissue. In most individuals particle concentrations in the larger airways show a clear increase in concentration with increasing airway generation (smaller airway diameter) as expected from deposition models; however, smoking disrupts this pattern in some subjects. Respiratory bronchioles accumulate particularly high particle loads, typically 25-100 times the concentrations seen in the mainstem bronchus. Similarly high concentrations are found in the large airway carinas, suggesting that these locations are likely sites for particle toxicity. The majority of particles in the airways in Vancouver lungs appear to be crustal in origin, with particular accumulation of silica in the airways compared to the parenchyma. Ultrafine particles, which have been postulated to be important in PM toxicity, are present in small numbers as singlet particles and are largely metals, perhaps representing combustion products, but carbonaceous chain aggregates are rarely found. Mean particle aerodynamic diameters vary from about 0.3 to 0.6 microm in different parts of the airways and, overall, the airways retain PM2.5 rather than PM10, a finding supporting the observation that, in some studies, adverse health effects appear to correlate better with PM2.5 than with PM10 concentrations. Preliminary examination of lungs of subjects from Mexico City, a location with relatively high ambient particle concentrations, indicates that the airway mucosa retains relatively large numbers of carbonaceous chain aggregates of ultrafine particles that appear to be combustion products and that presumably produce the numerous adverse effects documented for such products. Limited published data correlating visible particle load and airway mucus secretion, inflammation, and mural fibrosis suggest that high levels of air pollutant particles can induce chronic fibrotic responses in the airways, a phenomenon that might be linked to chronic airflow obstruction; this observation needs confirmation as well as correlation with specific types of particles. PMID- 11206333 TI - Chronic inflammatory demyelinating polyneuropathy: immunopathological and ultrastructural study of peripheral nerve biopsy in 42 cases. AB - The authors recently reexamined the peripheral nerve biopsies from 42 patients with chronic inflammatory demyelinating polyneuropathy (CIDP). There were 27 males and 15 females, aged from 9 to 84 years, and 13 had relapses. No patient had vasculitis, monoclonal gammopathy, tumor, diabetes mellitus, Lyme disease, familial neuropathy, HIV, or any other immune deficiency. In the endoneurium, perivascular inflammatory cell infiltrates were present in only one case, but scattered histiocytes marked by KP1 on paraffin-embedded fragments were present in every case and there were no T-lymphocytes. At ultrastructural examination macrophage-associated demyelination was observed in 17 cases, of which 6 had relapses separated by intervals of several months or years. Axonal lesions without associated primary demyelination were observed in 4 cases and 3 of these had relapses. Thirty-two patients had mixed lesions of demyelination and axonal involvement. This study confirms other recent data indicating that in all cases of CIDP, macrophages are present in the endoneurium. Macrophage-associated demyelination is the characteristic feature of demyelinating forms. On the other hand, isolated primary axonal forms, which have been known since 1989, are relatively frequent and prone to relapses. PMID- 11206334 TI - Phyllodes tumor of the breast: EGFR family expression and relation to clinicopathological features. AB - The expression of EGFR family members was examined by immunohistochemistry in 22 phyllodes tumors, and the results were evaluated together with immunohistochemical findings for proliferation markers Ki67 and BM28, and the tumor suppressor gene product p53. Light and electron microscopy were performed in all cases. Clinical information was obtained from the medial records. We did find that expression of EG FR, c-erbB-3 and c-erbB-4 proteins could be detected in the neoplastic mesenchymal cells, and that the expression increased with increasing malignancy. Increased expressions of Ki67, BM28, p53 and EGFR family members in neoplastic cells were associated with malignancy and unfavorable clinical course. Furthermore, the expression of ER-alpha and PR in the epithelial cells of phyllodes tumors was increased compared to that in normal breast epithelium. Finally, the application of electron microscopy helped to identify a group of malignant tumors, revealing neoplastic cells with characteristic nuclear indentations, as well as an increasing number of myofibroblasts. PMID- 11206335 TI - The continuing value of electron microscopy in surgical pathology. AB - For decades, transmission electron microscopy has played a valuable diagnostic role in surgical pathology. The continuing importance of electron microscopy, however, can be debated, given the major advances that have occurred in immunohistochemistry and other techniques. Electron microscopy retains excellent educational potential and broad research applicability, and it continues to be a necessity for the evaluation of a small subset of surgical pathology cases, such as renal biopsies and cilia specimens. The real controversy, then, centers on the contribution of electron microscopy in the evaluation of neoplasms. The opinion of many experts indicates that electron microscopy is still vital in the diagnostic assessment of some neoplasms, and that both electron microscopy and immunohistochemistry are more powerful when viewed as complementary rather than competitive techniques. For electron microscopy to be used to its potential, however, electron microscopists must function effectively as consultants. When optimally applied, electron microscopy remains an essential diagnostic tool. PMID- 11206336 TI - Composite keratohyaline granules in striate keratoderma. AB - The gross, light microscopic, and ultrastructural findings in a 55 year old man was striate keratoderma are presented. There was no family history of the disease. The lesions developed in his late teens and early adult years, and consisted of progressively worsening, raised, hyperkeratotic, linear plaques on the palm and volar surface of the third and fifth fingers bilaterally. There were also painful callosities on both heels, and thick, raised plaques on the heels and lateral plantar surfaces. The epidermis was papillomatous and acanthotic, with marked orthokeratosis, minimal parakeratosis, and a very thickened granular layer. No epidermolysis was seen. Electron microscopy showed increased tonofibrils in the stratum spinosum arranged in wavy, parallel bundles and a granular layer in which normal Odland bodies were present. However, the keratohyaline granules were large, with rounded borders and a striped, alternating, dark and light content characteristic of composite granules. There was diminished contact of the granules with tonofibrils. The transition to the stratum corneum was abrupt. The ultrastructural and genetic features of keratodermas, with special emphasis on the striate type, are reviewed. PMID- 11206337 TI - Ultrastructural identification of protein bodies, cellular markers of human catecholamine neurons, in a temporal lobe ganglioglioma. AB - A temporal lobe ganglioglioma, surgically removed from an 8-year-old body, and a human brainstem at the level of locus coeruleus (LC) were processed for light microscopy (LM), with formalin fixation and paraffin embedding, and for electron microscopy (EM) with glutaraldehyde fixation, potassium permanganate postfixation, phosphotungstic acid-hematoxylin block-staining, and epoxy resin embedding. The paraffin sections were stained with toluidine blue O/rhodamine B and observed under epi-fluorescence. The thin sections for EM were viewed directly without further staining. The neuronal neoplastic cells of ganglioglioma and the neurons of LC are known to produce catecholamines. Both also contain spherical protein bodies (pb), cellular markers that identify catecholamine neurons in humans. The ultrastructural characteristics of the pb in LC were compared with those of the pb in neoplastic ganglion cells. These bodies had an identical ultrastructure, in both tissues, consisting of electron-lucent core surrounded by an electron-dense thin rim. The rhodamine B-stained sections also emphasized the identical morphology of the pb in ganglioglioma and LC. Based on the EM comparison, these brightly fluorescing spherical bodies are ideal markers for identifying in LM, the clusters of large neoplastic cells, representing neurons, which are the most important clue to the correct diagnosis of gangliogliomas. PMID- 11206338 TI - Nemaline cardiomyopathy in a young adult: an ultraimmunohistochemical study and review of the literature. AB - Heart transplantation was performed in a 26-year-old man who suffered from severe dilatative cardiomyopathy. A nemaline myopathy characterized by the accumulation of Z-line material and the formation of rod-like structures had been diagnosed in the skeletal muscle. Routine light microscopy of the heart disclosed only nonspecific findings. On electron microscopy scattered cardiomyocytes showed formations of rod-like structures and a structural desintegration of contractile filaments near the intercalated disks. Immunocytochemistry at the light and electron microscopical level exhibited an accumulation of alpha-actinin, desmin, and occasionally vinculin in abnormal cardiomyocytes. The rods were specifically stained with alpha-actinin and were less immunoreactive for desmin. No mutations were revealed in the skeletal muscle alpha-actin gene. The results illustrate a complex derangement of the cytoskeletal apparatus in nemaline cardiomyopathy. Nemaline cardiomyopathy may be difficult to diagnose in routine diagnostic procedures. A close correlation between the severity of cardiac dysfunction and the morphological expression of the disease in the heart may not be found. Nemaline cardiomyopathy should be included in the differential diagnosis of dilatative cardiomyopathy and may be diagnosed with certainty by ultrastructural immunhistochemical investigations. PMID- 11206339 TI - Focal parietal cell differentiation in a well-differentiated (intestinal-type) early gastric cancer. AB - A well-differentiated (intestinal-type) early gastric cancer characterized by multifocal areas containing adenocarcinoma cells with eosinophilic cytoplasm is presented. The electron microscopy revealed that cytoplasmic eosinophilia was mainly due to the presence of numerous mitochondria. In addition, individual cells showed features of preparietal cell differentiation such as numerous mitochondria, tubulovesicles, intracellular canaliculi and rare mucin granules. There were also adenocarcinoma cells with a pyloric gland (mucopeptic) differentiation as revealed by the presence of granules with a dense protein core eccentrically located in the mucus matrix. These ultrastructural data suggested a gastric epithelial cell differentiation. The implications with regard to the classification and histogenesis of this tumor are discussed. PMID- 11206340 TI - Case for the panel. Crystalline cytoplasmic inclusions in an anaplastic oligodendroglioma. PMID- 11206341 TI - Early contributions to the study of bone and joint disease in Glasgow, Scotland. AB - Despite the fact that the University of Glasgow had a well-developed medical school founded in the eighteenth century, a modern rheumatology unit was only opened in 1965. However, Glasgow physicians, surgeons, and pathologists contributed to the study of bone and joint disease before this date. This paper is a summary of their contributions. PMID- 11206342 TI - Proteus IgG antibodies and C-reactive protein in English, Norwegian and Spanish patients with rheumatoid arthritis. AB - The distribution of Proteus antibody levels was compared in English, Norwegian and Spanish patients with rheumatoid arthritis (RA). Using an indirect immunofluorescence method, the IgG antibody titre against Proteus mirabilis was measured in the sera of 27 English, 53 Norwegian and 34 Spanish patients with RA and divided into active and inactive disease groups according to the serum C reactive protein (CRP) level (> or = 10 mg/l). Serum samples were also collected from 25 English, 30 Norwegian and 14 Spanish healthy individuals who served as controls. The levels of Proteus IgG antibodies were significantly higher in the sera of active RA patients (p<0.001) when compared with the corresponding healthy controls, whether these groups belonged to the English, Norwegian or Spanish populations. Furthermore, active RA patients from each country showed significantly higher levels of Proteus antibodies when compared with inactive English (p<0.01), Norwegian (p<0.001) or Spanish (p<0.001) RA patients. Finally, a significant correlation was observed between Proteus IgG antibody levels and the CRP concentrations in RA patients whether each population was tested individually or all together (p<0.001). The increased levels of Proteus antibodies in RA patients from three different European countries support the concept of a possible aetiopathogenetic role for Proteus microorganisms in the development of RA. PMID- 11206343 TI - Polyarteritis nodosa in Arab children in Saudi Arabia. AB - At both King Khalid University Hospital and King Faisal Specialist Hospital in Riyadh, Saudi Arabia, between 1990 and 1997, we identified 11 children with polyarteritis nodosa (PAN). Nine of them satisfied the American College of Rheumatology 1990 criteria for the classification of PAN. All patients were followed for at least 12 months. The male-to-female ratio was 1.8:1. Their mean age at disease onset was 5.8 years (range 2-11.5 years) and the mean duration of the disease was 2.5 years (range 1-7 years). The clinical presentations in the children were musculoskeletal symptoms in all patients, mucocutaneous findings in 10 (91%), fever in eight (73%), gastrointestinal manifestations in six (55%) and hypertension in five (45%). The most frequent laboratory findings were leucocytosis, anaemia, thrombocytosis and a high erythrocyte sedimentation rate. Both histopathological and angiographic findings were an effective means of diagnosis. Nine children responded to glucocorticoids (GC) with cytotoxic drugs while the rest improved on GC alone. None of the children died from the disease. A high index of suspicion with early combination therapy will help in decreasing the morality in these cases. PMID- 11206344 TI - Cervical and trochanteric hip fractures: bone mass and other parameters. AB - We examined 310 hip fracture patients (55 men, 255 women) to identify differences in those patients who had suffered a cervical fracture compared with those with a trochanteric fracture of the hip. Patients underwent a dual-energy X-ray absorptiometry (DXA) scan of their hip and total body and quantitative ultrasound (QUS) scans of their heel. Other measurements included medical/drug history. Significant differences were found for broadband ultrasound attenuation (BUA) and DXA total-body measurements, with those with a cervical fracture having a higher bone mass. Those with a trochanteric fracture showed a significantly higher incidence of stroke (12.8% vs. 6.3%, p = 0.05), while high blood pressure/antihypertensive therapy was significantly more common in the cervical fracture group (11.6% vs. 4.3%, p < 0.03). Therefore, it is not only bone parameters that differ in these patients. In the presence of certain medical conditions, preventative therapy may be directed to managing co-existing conditions as well as improving bone density. PMID- 11206345 TI - PFAPA syndrome (Periodic Fever, Aphthous stomatitis, Pharyngitis, Adenitis). AB - This paper aims to remind paediatric clinicians to suspect and confirm 'PFAPA' syndrome (Periodic Fever, Aphthous stomatitis, Pharyngitis and cervical Adenitis syndrome). We report two cases of PFAPA syndrome: a 3-year-old healthy boy with atopic rhinitis and a boy aged 8 years 5 months who simultaneously had lymphocytic vasculitis syndrome treated with immunosuppressive drugs. Both met Marshall's criteria. The literature regarding PFAPA syndrome was complied using a Medline search for articles published between 1963 and 1998 and we then reviewed the reference lists of the articles. The Medline search revealed 28 cases with available clinical manifestations, management and prognosis. Our study describes two additional cases. We divided the cases into typical (28 cases) and atypical (two cases) PFAPA syndrome. In typical PFAPA, the age of onset was less than 5 years in most cases and the patients presented 4.9 +/- 1.4 days of fever (100%), pharyngitis (89.3%), cervical adenitis (72.1%), stomatitis (71.4%), malaise (64.3%), headache (60.7%), abdominal pain (53.6%) and nausea/vomiting (17.9%). Afebrile intervals were 3.2 +/- 2.4 months and increased with age. The time from initial onset to final episode was 3 years 7 months +/- 3 years 6 months. The total number of episodes was 8.3 +/- 2.5 (range 6-14). Effective treatment included steroids, tonsillectomy/adenoidectomy and cimetidine. The general outcome was good. In atypical PFAPF, the clinical manifestations were similar to those of typical PFAPA except that the age of onset was more than 5 years, and life-threatening intestinal perforation happened once in a patient with underlying Fanconi's anaemia. It was concluded that typical PFAPA syndrome is benign and can be diagnosed by detailed history-taking and from physical findings during repeated febrile episodes with tests to rule out other periodic fever syndromes. A review of the literatures since the first report in 1987 has shown that typical PFAPA syndrome is not associated with significant long-term sequelae and has a good response to steroids. One patient with atypical PFAPA, who received low-dose steroids for over 1 year, developed intestinal perforation after an increment of the 7-day steroid dose. If an underlying problem requires long-term immunosuppressive medication, it is wiser to choose cimetidine rather than increasing the steroid dosage to resolve atypical PFAPA. PMID- 11206346 TI - Osteoarthricular involvement of brucellosis in Turkey. AB - The aim of this study was to determine the rates, types, clinical features and treatment of osteoarthricular involvement of brucellosis in Turkey. In a restrospective study in adults, we investigated 238 patients diagnosed with brucellosis over a period of 6 years. A diagnosis of brucellosis was established by isolation of Brucella species in blood or by a compatible clinical picture together with a standard tube agglutination titre of > or = 1/160 of antibodies for brucellosis and/or demonstration of an at least four-fold rise in antibody titre in serum specimens taken over 2 or 3 weeks. Osteoarthricular involvement was defined by inflammatory signs in peripheral joints or by unrelieved pain at rest together with radiological alterations and/or radionuclide uptake in any deep joint. Eighty-seven patients (36.5%) had osteoarthricular involvement (58.6% female, 41.4% male), 47 (54.1%) of whom were reported to consume unpasteurised dairy products. The mean age was 32.3 +/- 16 years. Sacroiliitis was the most common involvement (n = 53, 60.9%) followed by peripheral arthritis (n = 17, 19.5%), spondylitis (n = 12, 13.8%) and bursitis (n = 5, 5.7%). During the observation period, 60 (69%) patients with osteoarthricular involvement and radiographic abnormalities. A bone scan was positive in 15 patients with no radiographic abnormalities. All patients received merely medical treatment and relapse occurred in five (5.7%) patients. Sacroiliitis has been determined as the most frequently observed type of osteoarthricular involvement in brucellosis in Turkey. PMID- 11206347 TI - Juvenile chronic arthritis in adult life: a study of long-term outcome in patients with juvenile chronic arthritis or adult rheumatoid arthritis. AB - We compared the prognostic factors and outcome of 30 patients with juvenile chronic arthritis (JCA) extending into adult life with those of 30 patients with adult rheumatoid arthritis (RA) at a university adult rheumatology clinic; pairs were matched for sex and duration of disease (mean 8 years). One-third of JCA patients had seronegative polyarticular disease and another third had oligoarticular disease. In a third of the JCA patients, the clinical presentation changed during the follow-up. Over half of the RA patients had seropositive polyarticular and a one-third had seronegative polyarticular disease. Fewer seropositive patients were recorded in the JCA group than in the RA group both at the beginning (16.7% versus 56.7%; p=0.003) and at the end of the follow-up (14.3% versus 59.3%; p=0.001). JCA patients developed less radiographic changes than RA patients (46.7% versus 76.7%; p=0.034); oligoarthritis in the JCA group had the best prognosis whereas seropositive polyarthritis in the RA group had the worst prognosis. Significantly more patients with JCA than RA (60% versus 23%; p=0.009) were in remission at the end of the follow-up. In conclusion, when studied in adult life, the long-term prognosis is better in patients with JCA than in those with RA. PMID- 11206348 TI - Distribution of double-negative (CD4- CD8-, DN) T subsets in blood and synovial fluid from patients with rheumatoid arthritis. AB - Double-negative (CD4- CD8-) T (DNT) cells have been postulated to be potentially autoreactive. However, the role of DNT cells in rheumatoid arthritis (RA) has received limited attention. We investigated the distribution of DNT subsets in peripheral blood (PB) and synovial fluid (SF) from patients with active RA to determine whether these cells have relevance to RA. Two-colour flow cytometric analysis was performed to detect DNT cells in PB from 35 RA patients, 26 healthy controls and in SF aspirated from 19 inflamed rheumatoid joints. The subsets of DNT cells, i.e those expressing T cell receptor alphabeta (alphabeta DNT) or gammadelta (gammadelta DNT) were simultaneously examined. Our results showed that DNT cells constituted a very minor subset of PB lymphocytes. When expressed as a percentage of total lymphocytes, alphabeta DNT levels in normal individuals ranged from 0.27 to 2.08% (average 0.76%), while those of gammadelta DNT ranged from 1.02 to 11.42% (average 3.23%). Compared with normal individuals, RA patients had a similar distribution of alphabeta DNT cells in both PB and SF. However, RA patients had significantly lower levels of gammadelta DNT cells in PB than control subjects (1.38 +/- 1.08% vs 3.23 +/- 2.12%, p<0.05), while the levels of gammadelta DNT cells in SF of RA patients were higher than those in PB from RA patients and normal controls. The difference between PB and SF in RA was statistically significant (3.90 +/- 1.88% vs 1.38 +/- 1.08%, p<0.05). A higher level of gammadelta DNT in SF than their paired PB was consistently noted from nine available paired samples. Our findings suggest that gammadelta NT cells, but not alphabeta DNT cells, are probably relevant to RA. The lower percentage of circulating gammadelta DNT cells might have resulted from migration from the circulation into the synovium, suggesting a role for gammadelta DNT cells in the pathogenesis of rheumatoid synovitis. PMID- 11206349 TI - Degeneration of the scaphoid-trapezium joint: a useful finding to differentiate calcium pyrophosphate deposition disease from osteoarthritis. AB - This study aimed to determine whether osteoarthritis of the scaphoid-trapezium joint (ST osteoarthritis) is associated with calcium pyrophosphate deposition disease (CPDD) in an elderly population with or without concomitant polyarthritis of the finger joints (FIPO). An age- and gender matched case-control study was performed at a university hospital outpatient clinic. Cases and controls were identified from a clinical registry. The case ascertainment process included: (1) chart review for evidence of pyrophosphate crystals from arthrocentesis and/or cartilage calcifications and (2) blinded reading of hand X-rays by three observers for calcification of the triangular fibrocartilage and/or cartilage calcification around the spatium triangulare. Osteoarthritis was graded from 0 to 4 according to the Standard Atlas of Radiographs. The association of ST osteoarthritis with the diagnosis was examined using chi2 tests or the Wilcoxon rank sum test as appropriate. From 65 potential cases, 30 fulfilled the inclusion/exclusion criteria whereas from 185 potential controls, 81 fulfilled the inclusion/exclusion criteria. Thirty controls were matched to cases for gender and age. ST osteoarthritis was much more severe in CPDD (median: 3.0) than in patients with FIPO (median: 0.3) and was strongly associated with the diagnosis (odds ratio 13.8; CI 3.4-59.8). Definite ST osteoarthritis identified CPDD with a sensitivity of 83% and a specificity of 73% with regard to FIPO. It was concluded that the presence of ST osteoarthritis is a helpful diagnostic finding for the diagnosis of CPDD in an elderly, predominantly female population with a high prevalence of FIPO. Especially in cases without radiographic cartilage or fibrocartilage calcification of the wrist, ST osteoarthritis may point to the correct diagnosis. PMID- 11206350 TI - Marked improvement of severe cardiac dysfunction after one course of intravenous immunoglobulin in a patient with systemic lupus erythematosus. AB - Intravenous immunoglobulin (IVIg) is currently used with much enthusiasm for the treatment of many autoimmune diseases, including systemic lupus erythematosus (SLE). Among its various indications, IVIg has also been found to be beneficial in myocarditis, whether or not it is associated with an autoimmune disease (e.g. Kawasaki's disease). We report a 59-year-old SLE patient who, while being treated with steroids, developed severe cardiac dysfunction with a left ventricular ejection fraction of 20%. Coronary angiography demonstrating normal coronary arteries supported the diagnosis of myocarditis. High-dose IVIg treatment was started, followed by improved cardiac function a few days later and normalisation of the ejection fraction (50%) 1 month later. This is the second report of a beneficial effect of IVIg in myocarditis secondary to SLE. PMID- 11206351 TI - Thrombocytopenia in systemic-onset juvenile chronic arthritis: report of two cases with unusual bone marrow features. AB - Two children with systemic-onset juvenile chronic arthritis (S-JCA) suffering from severe, symptomatic thrombocytopenia are reported. Case 1 is a 10-year-old girl who had fever, chronic polyarthritis and hepatosplenomegaly for 6 months and severe gum bleeding and generalised petechiae for 1 week. Immune thrombocytopenic purpura (ITP) was indicated by bone marrow findings of megakaryocytic hyperplasia, and her thrombocytopenia responded well to steroid therapy without recurrence, but progressive, deforming polyarthritis with anaemia and thrombocytosis persisted. Case 2 is a 7-year-old girl who presented with spiking fever, arthritis and skin rashes and was suspected of having S-JCA. She developed a severe nosebleed with impending shock while receiving full-dose aspirin. Pancytopenia and elevated liver enzymes were also noted. Bone marrow aspiration revealed erythroid hyperplasia, maturation arrest of myeloid series with increased blasts, and adequate megakaryocytes. Her thrombocytopenia resolved in 1 week without specific treatment. Her subsequent clinical course confirmed the diagnosis of S-JCA, while thrombocytopenia did not recur during follow-up. PMID- 11206352 TI - Pure red cell aplasia in Felty's syndrome: a case report of successful reversal after cyclosporin A treatment. AB - We describe the first report of a patient with Felty's syndrome who developed pure red cell aplasia, likely not attributable to medication, that was successfully treated with cyclosporin A. PMID- 11206353 TI - Two siblings with juvenile hyaline fibromatosis: case reports and review of the literature. AB - In this paper, we describe two siblings with Juvenile Hyaline Fibromatosis (JHF) who were diagnosed at the age of 34 and 29 years respectively. JHF is a very congenital disease, mainly diagnosed in the first few years of life, with less than 40 published cases in literature. All the main clinical features of this syndrome, which may be summarised as multiple subcutaneous tumours, marked gingival hypertrophy, flexion contractures and osteolytic lesions were present in both of these cases. Clinical, radiological and histological differential diagnosis of JHF were made. Recent information about histopathology, treatment and prognosis of JHF was also reviewed. PMID- 11206354 TI - Burkitt's lymphoma presenting as ileocaecal intussusception in systemic lupus erythematosus. AB - Patients with systemic lupus erythematosus (SLE) are reported to have an increased risk of malignancy, especially lymphoproliferative disorders. We decribe the occurrence of ileocaecal intussusception secondary to Burkitt's lymphoma in a patient with SLE. A 23-year-old woman, who had been diagnosed with SLE 2 years ago, developed intermittent abdominal pain with a palpable mass. Computed tomography and a double-contrast barium enema showed a lobulated mass with intussusception at the ileocaecal junction. Right hemicolectomy and splenectomy was performed after histopathological examinations on colonoscopic biopsy revealed Burkitt's lymphoma. Fourteen months after chemotherapy, there is no evidence of recurrence of the Burkitt's lymphoma. When a patient with SLE has abdominal complaints, besides serositis, lupus enteritis such as peptic ulcer disease, mesenteric vasculitis with or without complications and pancreatitis, we have to consider intussusception secondary to gastrointestinal lymphoma as one of the differential diagnoses. Therefore, we should thoroughly investigate patients with SLE presenting with abdominal pain and not simply consider it afeature of lupus enteritis until other causes have been ruled out. PMID- 11206355 TI - Polyarteritis nodosa mimicking polymyalgia rheumatica. AB - We report a case of polyarteritis nodosa with a clinical presentation mimicking polymyalgia rheumatica, as well as pathological findings of non-giant-cell arteritis on temporal artery biopsy with symptoms of jaw claudication. Although certain clinical syndromes have been attributed to specific types of systemic vasculitis, considerable overlap occurs. Obtaining tissue biopsy in cases of vasculitis is mandatory for diagnosis and classification. PMID- 11206356 TI - Inflammatory bowel disease and myositis. AB - A patient with Crohn's disease developed proximal muscle weakness, increased serum creatine phosphokinase activity and electromyographic abnormalities. A muscle biopsy was non-diagnostic. Although rare, myositis should be included in the differential diagnosis of muscle weakness in patients with inflammatory bowel disease. PMID- 11206357 TI - Perceived risks of joint infection following intra-articular corticosteroid injections: a survey of rheumatologists. AB - There are no clear published data on the risks of bacterial arthritis following intra-articular corticosteroid injections. Forty rheumatologists were given a detailed questionnaire; 32 (response 80%) completed questionnaires were analysed. On the basis of recalled cases of post-injection joint infection we estimate this risk to be low, at 4.6/100,000 injections. PMID- 11206358 TI - Analgesic effect of intravenous pamidronate on chronic back pain due to osteoporotic vertebral fractures. AB - Pamidronate, a bisphosphonate analogue has been evaluated in a retrospective study for its analgesic effect on chronic back pain due to vertebral fractures in 26 patients suffering from senile osteoporosis or glucocorticoid-induced osteoporosis. Sixty milligrams of pamidronate was administered intravenously every 3 months for one year. After three months of treatment, the pain score fell from 3.2 +/- 0.1 to 1.2 +/- 0.2 in both groups. In conclusion, intravenous pamidronate seems to be a valuable treatment for chronic back pain due to osteoporotic vertebral fractures. PMID- 11206359 TI - Antineutrophil cytoplasmic antibody in patients with primary Sjogren's syndrome. AB - The incidence, specificity and clinical significance of positivity for serum antineutrophil cytoplasmic antibody (ANCA) was investigated in 60 patients with primary Sjogren's syndrome (SjS). The indirect immunofluorescence (IIF) technique and an enzyme-linked immunosorbent assay (ELISA) were used to measure ANCA. Purified myeloperoxidase (MPO), lactoferrin (LF), cathepsin-G (CTG) and elastase (HLE) served as ANCA antigens for the ELISA. Ten (16.7%) of the 60 SjS patients showed positivity by IIF for perinuclear, but not cytoplasmic, ANCA. Four of the 60 sera were shown to be positive for LF, four for MPO, 0 for CTG and 0 for HLE by ELISA. There was no correlation between ANCA positivity and clinical features. ANCA in patients with SjS might be an epiphenomenon of polyclonal B-cell activation. PMID- 11206360 TI - Benchmarking of model core potentials: application to the halogen complexes of group 4 metals. AB - The reliability of the model core potential (MCP) method was probed in a systematic RHF and MP2 study of the geometries of the group 4 metal halogen complexes (MX4; M = Ti, Zr, Hf and X = F, Cl, Br, I). The computed bond lengths were compared with experimental values, as well as those predicted using effective core potentials. Provided that electrons from the outermost core shell of the metal atom are treated explicitly in the calculation, both the MCP and ECP methods predict M-X bond lengths within 0.02-0.03 A of experiment. The reaction energies for a simple set of halogen substitution reactions of the MX4 complexes leading to the mixed halogen complex, MX2Y2, were also studied. Although no experimental values are available for these reactions, comparison was made with the values computed using effective core potentials. The predictability of the different pseudopotential techniques and the importance of the metal atom valence basis set contraction scheme and polarization space are discussed. PMID- 11206361 TI - CheD: chemical database compilation tool, Internet server, and client for SQL servers. AB - An efficient program, which runs on a personal computer, for the storage, retrieval, and processing of chemical information, is presented, The program can work both as a stand-alone application or in conjunction with a specifically written Web server application or with some standard SQL servers, e.g., Oracle, Interbase, and MS SQL. New types of data fields are introduced, e.g., arrays for spectral information storage, HTML and database links, and user-defined functions. CheD has an open architecture; thus, custom data types, controls, and services may be added. A WWW server application for chemical data retrieval features an easy and user-friendly installation on Windows NT or 95 platforms. PMID- 11206362 TI - Spiral codes and Goldberg representations of icosahedral fullerenes and octahedral analogues. AB - An icosahedral fullerene may be considered as a tessellation of the sphere specified by an ordered pair of integers, or as a tightly wound spiral of faces. Explicit analytical relations for interconverting the two representations are given, enabling the canonical spiral code to be constructed for an icosahedral fullerene of any size. Analogous relations hold for the octahedral square + hexagon polyhedra that have been mentioned as possible candidates for boron nitride "fullerenes". PMID- 11206363 TI - Spectral moments of phenylenes. AB - In a series of publications Estrada (Estrada, E. J. Chem. Inf. Comput. Sci. 1996, 36, 844-849; 1997 37, 320-328; 1998, 38, 23-27) employed spectral moments of line graphs in QSPR and QSAR relationship studies of various classes of compounds. A recent paper (Markovic, S.; Gutman, I. J. Chem. Inf Comput. Sci. 1999, 39, 289 293) reported that in QSPR and QSAR investigations of benzenoid hydrocarbons based on linear combination of spectral moments, it made no difference whether one used spectral moments of the molecular graph or those of the line graph. In the present work spectral moments of molecular graphs (Mk) and line graphs (muk) of phenylenes are considered. The first few Mk's and muk'S of phenylenes are dependent on identical structural parameters. It is proved that the two sets of moments of phenylenes are linearly dependent. It is also shown that in the case of the heat of formation of phenylenes there is no advantage in using lower spectral moments of line graphs instead of lower spectral moments of molecular graphs. In this way the redundancy observed in the case of benzenoid hydrocarbons is also shown to exist in the class of phenylenes. PMID- 11206364 TI - High-throughput prediction of blood-brain partitioning: a thermodynamic approach. AB - A high-throughput in silico screening tool for potentially CNS active compounds was developed on the basis of the correlation of solvation free energies and blood-brain partitioning (log(cbrain/cblood) = log BB) data available from experimental sources. Utilizing a thermodynamic approach, solvation free energies were calculated by the fast and efficient generalized Born/surface area continuum solvation model, which enabled us to evaluate more than 10 compounds/min. Our training set involved a structurally diverse set of 55 compounds and yielded a function of log BB = 0.035Gsolv + 0.2592 (r = 0.85, standard error 0.37). Calculation of solvation free energies for 8700 CNS active compounds (CIPSLINE database) revealed that Gsolv is higher than -50 kJ/mol for the 96% of these compounds which can be used as suitable criteria for the identification of compounds preferable for CNS penetration. PMID- 11206365 TI - Determining the number of resonance structures in concealed non-Kekulean benzenoid hydrocarbons. AB - The number of resonance structures (SC) for previously published concealed non Kekulean benzenoid hydrocarbons is determined. Using a simple computer program, analytical expressions for determining SC for various classes of non-Kekulean (free-radical) benzenoid hydrocarbons are derived, and some properties of concealed non-Kekulean benzenoid hydrocarbons are studied. PMID- 11206366 TI - Ties in proximity and clustering compounds. AB - Hierarchical clustering algorithms such as Wards or complete-link are commonly used in compound selection and diversity analysis. Many such applications utilize binary representations of chemical structures, such as MACCS keys or Daylight fingerprints, and dissimilarity measures, such as the Euclidean or the Soergel measure. However, hierarchical clustering algorithms can generate ambiguous results owing to what is known in the cluster analysis literature as the ties in proximity problem, i.e., compounds or clusters of compounds that are equidistant from a compound or cluster in a given collection. Ambiguous ties can occur when clustering only a few hundred compounds, and the larger the number of compounds to be clustered, the greater the chance for significant ambiguity. Namely, as the number of "ties in proximity" increases relative to the total number of proximities, the possibility of ambiguity also increases. To ensure that there are no ambiguous ties, we show by a probabilistic argument that the number of compounds needs to be less than 2(n 1/4), where n is the total number of proximities, and the measure used to generate the proximities creates a uniform distribution without statistically preferred values. The common measures do not produce uniformly distributed proximities, but rather statistically preferred values that tend to increase the number of ties in proximity. Hence, the number of possible proximities and the distribution of statistically preferred values of a similarity measure, given a bit vector representation of a specific length, are directly related to the number of ties in proximities for a given data set. We explore the ties in proximity problem, using a number of chemical collections with varying degrees of diversity, given several common similarity measures and clustering algorithms. Our results are consistent with our probabilistic argument and show that this problem is significant for relatively small compound sets. PMID- 11206367 TI - Novel chirality descriptors derived from molecular topology. AB - Several series of novel chirality descriptors of chemical organic molecules have been introduced. The descriptors have been developed on the basis of conventional topological descriptors of molecular graphs. They include modified molecular connectivity indices, Zagreb group indices, extended connectivity, overall connectivity, and topological charge indices. These modified descriptors make use of an additional term called chirality correction, which is added to the vertex degrees of asymmetric atoms in a molecular graph. Chirality descriptors can be real or complex numbers. Advantages and drawbacks of different series of chirality descriptors are discussed. These descriptors circumvent the inability of conventional topological indices to distinguish chiral or enantiomeric isomers, which so far has been the major drawback of 2D descriptors as compared to true 3D descriptors (e.g., shape, molecular fields) of molecular structure. These novel chirality descriptors have been implemented in a quantitative structure-activity releationship (QSAR) study of a set of ecdysteroids with a high content of chiral and enantiomeric compounds using the k nearest neighbor QSAR method (kNN) recently developed in this laboratory. We show that the results of this study compare favorably with those obtained with the comparative molecular field analysis (CoMFA) applied to the same dataset. The novel chirality descriptors of molecular structure should find their applications in QSAR studies and related investigations of molecular sdatasets. PMID- 11206368 TI - A constant time algorithm for estimating the diversity of large chemical libraries. AB - We describe a novel diversity metric for use in the design of combinatorial chemistry and high-throughput screening experiments. The method estimates the cumulative probability distribution of intermolecular dissimilarities in the collection of interest and then measures the deviation of that distribution from the respective distribution of a uniform sample using the Kolmogorov-Smirnov statistic. The distinct advantage of this approach is that the cumulative distribution can be easily estimated using probability sampling and does not require exhaustive enumeration of all pairwise distances in the data set. The function is intuitive, very fast to compute, does not depend on the size of the collection, and can be used to perform diversity estimates on both global and local scale. More importantly, it allows meaningful comparison of data sets of different cardinality and is not affected by the curse of dimensionality, which plagues many other diversity indices. The advantages of this approach are demonstrated using examples from the combinatorial chemistry literature. PMID- 11206369 TI - Results of a new classification algorithm combining K nearest neighbors and recursive partitioning. AB - We present results of a new computational learning algorithm combining favorable elements of two well-known techniques: K nearest neighbors and recursive partitioning. Like K nearest neighbors, the method provides an independent prediction for each test sample under consideration, while like recursive partitioning, it incorporates an automatic selection of important input variables for model construction. The new method is applied to the problem of correctly classifying a set of chemical data samples designated as being either active or inactive in a biological screen. Training is performed at varying levels of intrinsic model complexity, and classification performance is compared to that of both K nearest neighbor and recursive partitioning models trained using the identical protocol. We find that the cross-validated performance of the new method outperforms both of these standard techniques over a considerable range of user parameters. We discuss advantages and drawbacks of the new method, with particular emphasis on its parameter robustness, required training time, and performance with respect to chemical structural class. PMID- 11206370 TI - A novel method for building regression tree models for QSAR based on artificial ant colony systems. AB - Among the multitude of learning algorithms that can be employed for deriving quantitative structure-activity relationships, regression trees have the advantage of being able to handle large data sets, dynamically perform the key feature selection, and yield readily interpretable models. A conventional method of building a regression tree model is recursive partitioning, a fast greedy algorithm that works well in many, but not all, cases. This work introduces a novel method of data partitioning based on artificial ants. This method is shown to perform better than recursive partitioning on three well-studied data sets. PMID- 11206371 TI - Combined pseudopotential and density functional study of Bis-eta6-benzene d and f element complexes. AB - The electronic and molecular structures of selected zerovalent d and f metal bis eta6-benzene sandwich complexes M(C6H6)2 (M = Sc, Ti, V, Cr, Y, Zr, Nb, Mo, La, Ce, Gd, Lu, Hf, Ta, Nb, Th) were investigated at the scalar-relativistic level using a combination of energy-consistent ab initio pseudopotentials and gradient corrected density functionals. The results are compared to previous pseudopotential coupled-cluster and all-electron density functional results based on the zero-order regular approximate Hamiltonian of Chang, Pelissier, and Durand as well as to experimental data. PMID- 11206372 TI - Algorithm for naming molecular equivalence classes represented by labeled pseudographs. AB - The emergence of large chemical databases imposes a need for organizing the compounds in these databases. Mapping the chemical graph in particular, and a molecular equivalence class represented by a labeled pseudograph in general, to a unique number or string facilitates high-throughput browsing, grouping, and searching of the chemical database. Computing this number using a naming adaptation of the Morgan algorithm, we observed a large classification noise in which nonisomorphic graphs were mapped to the same number. Our extensions to that algorithm greatly reduced the classification noise. PMID- 11206373 TI - QSAR models using a large diverse set of estrogens. AB - Endocrine disruptors (EDs) have a variety of adverse effects in humans and animals. About 58,000 chemicals, most having little safety data, must be tested in a group of tiered assays. As assays will take years, it is important to develop rapid methods to help in priority setting. For application to large data sets, we have developed an integrated system that contains sequential four phases to predict the ability of chemicals to bind to the estrogen receptor (ER), a prevalent mechanism for estrogenic EDs. Here we report the results of evaluating two types of QSAR models for inclusion in phase III to quantitatively predict chemical binding to the ER. Our data set for the relative binding affinities (RBAs) to the ER consists of 130 chemicals covering a wide range of structural diversity and a 6 orders of magnitude spread of RBAs. CoMFA and HQSAR models were constructed and compared for performance. The CoMFA model had a r2 = 0.91 and a q2LOO = 0.66. HQSAR showed reduced performance compared to CoMFA with r2 = 0.76 and q2LOO = 0.59. A number of parameters were examined to improve the CoMFA model. Of these, a phenol indicator increased the q2LOO to 0.71. When up to 50% of the chemicals were left out in the leave-N-out cross-validation, the q2 remained significant. Finally, the models were tested by using two test sets; the q2pred for these were 0.71 and 0.62, a significant result which demonstrates the utility of the CoMFA model for predicting the RBAs of chemicals not included in the training set. If used in conjunction with phases I and II, which reduced the size of the data set dramatically by eliminating most inactive chemicals, the current CoMFA model (phase III) can be used to predict the RBA of chemicals with sufficient accuracy and to provide quantitative information for priority setting. PMID- 11206374 TI - Computational modeling of a binding conformation of the intermediate L-histidinal to histidinol dehydrogenase. AB - Histidinol dehydrogenase (HDH) is one of the enzymes involved in the L-histidine biosynthesis pathway. HDH is a dimer that contains one Zn2+ ion in each identical subunit. In this study, we predicted a possible binding conformation of the intermediate L-histidinal, which is experimentally not known, using a computational modeling method and three potent HDH inhibitors whose structures are similar to that of L-histidinal. At first, a set of the most probable active conformations of the potent inhibitors was determined using two different pharmacophore mapping techniques, the active analogue approach and the distance comparison method. From the most probable active conformations of the three potent inhibitors, the common parts of the L-histidinal structure were extracted and refined by energy minimization to obtain the binding conformation of L histidinal. This predicted conformation of L-histidinal agrees with an experimentally determined conformation of L-histidine in a single crystal, suggesting that it is an experimentally acceptable conformation. The capability in this conformation to coordinate a Zn2+ ion was examined by comparing the spatial relative geometry of its functional groups with those of ligands that coordinate with a Zn2+ ion in Zn proteins of the Protein Data Bank. This comparison supported our predicted conformation. PMID- 11206375 TI - Analysis of the internal representations developed by neural networks for structures applied to quantitative structure--activity relationship studies of benzodiazepines. AB - An application of recursive cascade correlation (CC) neural networks to quantitative structure-activity relationship (QSAR) studies is presented, with emphasis on the study of the internal representations developed by the neural networks. Recursive CC is a neural network model recently proposed for the processing of structured data. It allows the direct handling of chemical compounds as labeled ordered directed graphs, and constitutes a novel approach to QSAR. The adopted representation of molecular structure captures, in a quite general and flexible way, significant topological aspects and chemical functionalities for each specific class of molecules showing a particular chemical reactivity or biological activity. A class of 1,4-benzodiazepin-2-ones is analyzed by the proposed approach. It compares favorably versus the traditional QSAR treatment based on equations. To show the ability of the model in capturing most of the structural features that account for the biological activity, the internal representations developed by the networks are analyzed by principal component analysis. This analysis shows that the networks are able to discover relevant structural features just on the basis of the association between the molecular morphology and the target property (affinity). PMID- 11206376 TI - Use of 13C NMR spectrometric data to produce a predictive model of estrogen receptor binding activity. AB - We have developed a spectroscopic data-activity relationship (SDAR) model based on 13C NMR spectral data for 30 estrogenic chemicals whose relative binding affinities (RBA) are available for the alpha (ERalpha) and beta (ERbeta) estrogen receptors. The SDAR models segregated the 30 compounds into strong and medium binding affinities. The SDAR model gave a leave-one-out (LOO) cross-validation of 90%. Two compounds that were classified incorrectly in the SDAR model were in the transition zone between classifications. Real and predicted 13C NMR chemical shifts were used with test compounds to evaluate the predictive behavior of the SDAR model. The 13C NMR SDAR model using predicted 13C NMR data for the test compounds provides a rapid, reliable, and simple way to screen whether a compound binds to the estrogen receptors. PMID- 11206377 TI - Applications of effective core potentials and density functional theory to the spin states of iron porphyrin. AB - We investigated the performance of the B3LYP density functional in combination with ab initio effective core potentials (ECPs) that are derived from either Hartree-Fock or Dirac-Fock calculations. The transferability of ab initio ECPs is assessed on the basis of comparison with all-electron density functional calculations. For iron(II) porphyrin in particular, our assessment focused on the relative energetic ordering of five low-lying spin states, 1A1G, 3A1G, 3B2G, 5A2G, and 5B1G, and their properties, including optimized structures, charge distribution, spin density, and vibrational frequencies. Our results show that core electron correlation and core-valence electron correlation do not have significant effects on the relative energetics of the spin states of iron porphyrin. Our calculations suggest that effects of replacing the core electrons with ECPs are less significant than the choice of basis functions. We conclude that ab initio ECPs such as LANL2, RCEP, and MEFIT-R may be combined with the B3LYP density functional theory to provide consistent and accurate results. PMID- 11206378 TI - A QSPR study of the 31P NMR chemical shifts of phosphines. AB - Quantitative structure-property relationships (QSPR) on a large set of descriptors are developed for the 31P NMR chemical shifts of a large set of phosphines. The data set was composed of 291 primary, secondary, and tertiary phosphines, PH3-nRn, including substituents with different steric and electronic characteristics. Multiple linear regression and computational neural networks (CNN) were employed to create the models best suited for the prediction of 31P NMR chemical shifts. A correlation equation including seven descriptors (R2 = 0.8619) is reported. A 7-5-1 CNN was developed that produced a root-mean-error of 9.6 ppm (R2 = 0.9513) for the training set, of 11.7 ppm (R2 = 0.8986) for the cross-validation set, and of 11.3 ppm (R2 = 0.9527) for an external prediction set. The CNN methods give significantly better predictions of 31P NMR chemical shifts for phosphines than the multiple linear regression approach. PMID- 11206379 TI - Formal analysis of effective core potential methods. AB - Effective core potentials are analyzed from the standpoint of the underlying frozen core approximation. The content of the pseudoorbital, the content of the potential, and the properties of both are elaborated, showing the points at which they differ from the frozen core approximation and where possible deficiencies might lie. PMID- 11206380 TI - Modeling intermolecular effects on nonlinear optical properties of transition metal complexes. An effective core potential study. AB - An initial effort to study the nonlinear optical (NLO) properties of interacting transition-metal-oxo complexes is presented and studied by effective core potential approaches. Osmium tetroxide is used for this study. Favorable intermolecular interaction effects, even within this weak interaction regime, that yield enhancements in NLO properties have been found. Interaction effects increase alpha (polarizability) up to 6% and gamma (second hyperpolarizability) up to 100% relative to the isolated monomer result for OsO4. The magnitude of the interaction (hyper)polarizabilities, and indeed even the sign, is found to be quite sensitive to the relative orientation of the osmium tetroxide monomers. PMID- 11206381 TI - Recent progress in atomic and chemical group effective potentials. AB - Recent progress on atomic and chemical group effective potentials is presented. The reviewed effective potentials follow a shape-consistent extraction technique from ab initio data, within a scalar relativistic approximation. Two types of averaged relativistic effective core potentials are considered: the correlated ones where a part of the correlation energy is included in the effective potential, and the polarized ones for which only the core polarization effects are taken into account. In addition spin-orbit polarized pseudopotentials have been extracted, and the effects of the core polarization are tested on the atomic spectroscopy of iodine. Finally a very recent chemical group effective methodology is presented, reducing the number of both electrons and nuclei explicitly treated. Chemical transferability is investigated, and test calculations on a cyclopentadienyl effective group potential are presented. PMID- 11206382 TI - A computational study of the effectiveness of the frontier molecular orbital formalism in predicting conformational isomerism in (p-RC6H4NC)2W(dppe)2. AB - Ab initio electronic structure calculations on a series of ligands, p-RC6H4NC:, indicate, that the energy of the LUMO correlates with the electron withdrawing/donating capabilities of the substituent group, which determines the relative pi-acidity of the ligand. Depending on the nature of the para substituent group on the aryl isocyanide ligand, bis(aryl isocyanide) complexes of tungsten-containing bulky bidentate arylphosphine ligands adopt either cis or trans conformations. The frontier molecular orbital formalism predicts that strong pi-acids, which contain electron-withdrawing groups, tend to polarize sufficient charge density away from the metal center to effect the formation of the sterically less favorable but electronically stabilized cis conformer. Density functional theory calculations on similar complexes containing phosphines which do not impose severe steric contraints indicate that the balance between steric and electronic stabilization can be effectively predicted by comparing the relative energies of the ligand LUMOs. PMID- 11206383 TI - DFT/ECP study of C-H activation by (PCP)Ir and (PCP)Ir(H)2(PCP=eta3-1,3 C6H3(CH2PR2)2). Enthalpies and free energies of associative and dissociative pathways. AB - (PCP)Ir(H)2 (PCP = eta3-1,3-C6H3(CH2PR2)2) complexes are highly effective catalysts for the dehydrogenation of alkanes; in particular, they are the first efficient molecular catalysts for alkane dehydrogenation that do not require a sacrificial hydrogen acceptor. Using density functional theory/effective core potential methods, we have examined C-H bond cleavage in alkanes and arenes by both (PCP)Ir and (PCP)Ir(H)2. C-H addition to the dihydride is accompanied by loss of H2; both associative and dissociative pathways for this exchange reaction have been examined. The energetic barrier (deltaE(is not equal)) for associative displacement of H2 by benzene is much lower than the barrier for a dissociative pathway involving initial loss of H2; however, the pathways have very comparable free energy barriers (deltaG(is not equal)). Extrapolation to the higher temperatures, bulkier phosphine ligands, and the alkane substrates used experimentally leads to the conclusion that the pathway for the "acceptorless" dehydrogenation of alkanes is dissociative. For hydrocarbon/hydrocarbon exchanges, which are required for transfer-dehydrogenation, dissociative pathways are calculated to be much more favorable than associative pathways. We emphasize that it is the free energy, not just the internal energy or enthalpy, that must be considered for elementary steps that show changes in molecularity. PMID- 11206384 TI - Nodeless valence (pseudo)spinors. AB - Atomic calculations using small-core relativistic effective core potentials (RECPs) explicitly treating outer core electrons are used to define two-component nodeless valence spinors (NVSs) and nodeless valence pseudospinors (NVPSs). Errors attributable to nonlocal electron repulsion interactions that arise from large-core RECPs are shown to result from the inherent arbitrariness in the choice of match points and number of derivatives that define shape-consistent pseudospinors, as well as the positions of radial nodes that reside in the outer core regions of atoms. Self-consistent field calculations in omegaomega-coupling for InH and InCl using RECPs derived from NVSs and NVPSs are reported. Increased bond distances relative to those calculated using very-large-core RECPs for In agree with those due to frozen 4d(3/2) and 4d(5/2) spinors and a small-core RECP. Results for AmCl+2 also reveal that the shortening in the bond length is recovered when the very-large-core RECP is derived using nodeless valence (pseudo)spinors. PMID- 11206385 TI - Ab initio structure of the active site of phosphotriesterase. AB - This research exploits two recent developments to obtain a fundamental understanding of the metalloenzyme active site using the bimetallic enzyme phosphotriesterase as an example of this class. First is the theoretical prediction that the structure and spectroscopy of a native metalloenzyme active site is qualitatively determined by the supermolecule complex of the metal(s) and the first shell of ligands with proper charge states including waters directly bonded to ionic ligands. The second is the development of an effective potential for representing the molecular environment interacting with an all-electron active site in the quantum Hamiltonian. The GAMESS suite of electronic structure codes has implemented this new methodology, effective fragment potentials (EFP), to make theoretical calculations on structure, spectroscopy, and reactivity tractable for systems involving hundreds of atoms. Since there are transition metal cations at the active site of these enzymes, the all-electron part of the complex is calculated with relativistic compact effective potentials (CEP) and their concomitant basis sets. A realistic representation of the active site with its protein environment can be obtained using a combination of the CEP and EFP. This presentation will determine the inherent electronic and structural characteristics of phosphotriesterase using ab initio quantum mechanical methods. A single X-ray structure for the Zn-Zn enzyme is leveraged to obtain the structure of the Cd-Cd enzyme and to examine the consequences of protonating the active site. PMID- 11206386 TI - Solving incomplete inorganic chemical systems through a fuzzy knowledge frame. AB - A model for the completion and balancing of inconsistent inorganic reactions is presented. A series of fuzzy parameters is proposed. These parameters are considered within a knowledge frame representing inorganic reactions via a semantic/functional network and, through the calculation of possibility measures, allow the completion and solution of such reactions by considering new inorganic species to be added to the reaction. Species to be added are formulated on the basis of atoms present and/or absent in the reaction, along with valence, system features, and a series of flags that determines the cardinality of the possible solution set. Incorporation of the proposed model into an inorganic chemistry formulation system would contribute to the development of powerful computer assisted learning systems, given the extent of information extracted from a reaction. PMID- 11206387 TI - Relativistic pseudopotentional incorporating core/valence polarization and nonlocal effects. AB - A relativistic pseudopotentional (RPP) for use in ab initio molecular electronic structure calculations is derived in the context of the relativistic effective core potential (REP) method of Lee et al. The resulting atom-specific RPP has salient features of the REP imbedded within it while retaining the form of a functional that is dynamically defined at runtime when used in calculations on molecules. The RPP is determined from Dirac-Fock wave functions for the isolated atom. Outer core two-electron interactions are incorporated into the RPP by means of variable coefficients that are defined in the context of the final molecular wave function. This form permits polarization of the outer core shells analogous to that occurring in all-electron molecular Hartree-Fock calculations while retaining these shells as part of the atomic pseudopotentional. Use of the RPP in post-Hartree-Fock molecular calculations permits the incorporation of core/valence correlation effects. PMID- 11206388 TI - Capsular serogroups of Pasteurella multocida isolated from animals in Zimbabwe. AB - Pasteurella multocida is isolated from a variety of disease conditions from different animal species in our diagnostic laboratory. In order to determine serogroup distribution among the isolates, an indirect haemagglutination test using glutaraldehyde-fixed sheep red blood cells was employed. A serological examination of 79 isolates revealed that 47/79 were of capsular serogroup A, 11/79 capsular serogroup D, 4/79 capsular serogroup B and 17/79 were untypable strains. None of the isolates belonged to either serogroup E or F. All those from cases of classical pasteurellosis could be grouped, but a significantly high proportion of those which originated from companion animals were untypable. The significance of these results is discussed. This report appears to be the first detailed information on the prevalence of various serogroups of P. multocida in animals in southern Africa. PMID- 11206390 TI - Efficacy of flumethrin 1% pour-on against ticks on cattle under field conditions in Ethiopia. AB - The efficacy of a flumethrin 1% pour-on (Bayticol, Bayer AH) was evaluated against natural infestations of ticks on cattle on a dairy farm in Ethiopia during 1997/98. The cattle, (n = 92), which were Friesian/ Zebu crosses, were heavily infested with Boophilus decoloratus. Dry cows (n = 8) were randomly selected and allocated either into a treatment or a control group. Flumethrin 1 % pour-on was applied to the treatment group according to the manufacturer's recommendation, i.e. along the dorsal mid-line from the head to the base of the tail. Ticks were counted and identified in situ on treated and control animals. When the total tick counts of the treated group were similar to those on the control, the trial was discontinued. Excellent results were achieved with flumethrin against heavy tick infestations. There was a rapid kill after 24 h post-treatment, and from day 4 onwards 100% control was achieved and maintained for a further 29 days. The results obtained indicate that there was a significant difference between the mean tick counts of the control group compared with those of the treatment group (P < 0,05). The evidence presented here suggests that the flumethrin 1 % pour-on may be applied at 45 day intervals and should provide effective protection against the economically important ticks if it is used at the recommended dosage rate and applied correctly. PMID- 11206389 TI - Studies on the genus Setaria Viborg, 1795 in South Africa. I. Setaria africana (Yeh, 1959). AB - Setaria africana (Yeh, 1959) is represented by two subspecies, Setaria africana africana Troncy, Graber & Thal, 1976 from giant eland (Taurotragus derbianus) from the Central African Republic and Cameroon and Setaria africana farchai Troncy, Graber & Thal, 1976 from bushbuck (Tragelaphus scriptus), also from the Central African Republic. Material collected from nyala (Tragelaphus angasii), bushbuck and kudu (Tragelaphus strepsiceros) from several localities in the eastern region of South Africa was re-examined. Measurements of adult worms confirmed the differences between the two subspecies and scanning electron microscopy showed that the deirids of S. africana africana are single whereas those of S. africana farchaiare double. Setaria africana farchaiis recorded for the first time in South Africa. PMID- 11206391 TI - Parasites of domestic and wild animals in South Africa. XXXVIII. Ixodid ticks collected from 23 wild carnivore species. AB - Ixodid ticks were collected from 104 wild carnivores belonging to 23 species in various nature reserves and on several farms in all nine provinces of South Africa. Seven feral cats in a nature reserve were also examined. Twenty-four tick species belonging to seven genera were recovered and identified. Amongst these ticks we consider the adults of Haemaphysalis leachi, Haemaphysalis spinulosa, Haemaphysalis zumpti, Ixodes rubicundus, Rhipicentor nuttalli, Rhipicephalus simus and Rhipicephalus turanicus to be true parasites of wild carnivores. Although numerous adult Rhipicephalus appendiculatus and Rhipicephalus zambeziensis were collected from some lions these were either sick or old animals. The immature stages of seven species regularly utilized wild carnivores as hosts on an opportunistic basis. PMID- 11206392 TI - Application of ultrasonography in prevalence studies of hydatid cysts in goats in north-western Turkana, Kenya and Toposaland, southern Sudan. AB - A study was done to determine the prevalence of hydatid cysts in goats using ultrasonography. A total of 1,390 goats were examined, 43,6 % (606/1,390) of them from north-western Turkana, Kenya, and 56,4% (784/1,390) from Toposaland, southern Sudan. Hydatid cysts were visualized in 1,82 % (11/ 606) of the goats from north-western Turkana and 4,34% (34/784) of those from Toposaland. Unlike abattoir surveys, the prevalence data obtained in this study were unbiased because entire flocks were examined. The lower prevalence rate of the disease in goats from Turkana was attributed to the hydatid disease control programme in that area, which is absent in Toposaland. PMID- 11206393 TI - Fertility in rats immunized with steroid-free bovine follicular fluid. AB - Inhibin is a gonadal hormone that inhibits the release of follicle stimulating hormone (FSH) from the anterior pituitary gland. The objective of this study was to determine whether active immunization of male and female rats against inhibin rich, steroid-free bovine follicular fluid would increase inhibin antibody titre, onset of female puberty, pregnancy rate, litter size, testis weights, testosterone concentration and serum FSH. Immunization of rats with steroid free bovine follicular fluid stimulated production of anti-inhibin antibodies that immunoneutralized endogenous inhibins and increased levels of circulating FSH in immunized males. Inhibin immunoneutralization resulted in early vaginal opening in immunized females compared with controls and pregnancy rates were increased when immunized female rats were mated with immunized males. However, serum testosterone, testis weights and potential litter size remained unchanged. We conclude that methods to immunoneutralize inhibin may have merit as therapeutic procedures to enhance reproductive performance in domestic animals. PMID- 11206394 TI - Parameters for the determination and evaluation of heat stress in dairy cattle in South Africa. AB - Not all parameters are trustworthy and practical to use as parameters to determine heat stress in dairy cattle. The temperature-humidity index (THI) is still the best, simplest and most practical index (parameter) for measurement of environmental warmth which cause heat stress in dairy cattle. It is practical, easy to determine and relatively trustworthy to use body temperature and respiratory rate as parameters to determine heat stress in dairy cattle. These physiological parameters must always be used together with THI values to determine and evaluate heat stress in dairy cattle. For practical purposes, plasma cortisol concentration and milk composition cannot be used as parameters to determine heat stress in dairy cattle although good indications of acute or chronic heat stress can be obtained. Vanillic acid is a break-down product of adrenalin found in milk, but before its concentration in milk can be used as an indicator/parameter of heat stress in dairy cows, more about the pharmacodynamics of adrenaline in the milk has to be known. Selection and breeding of dairy cows on the basis of their adaptibility to heat stress using the most practical heat stress parameters will ensure that their offspring will have superior performance in the prevailing environmental conditions. PMID- 11206395 TI - In vitro erythrophagocytosis by cultured macrophages stimulated with extraneous substances and those isolated from the blood, spleen and bone marrow of Boran and N'Dama cattle infected with Trypanosoma congolense and Trypanosoma vivax. AB - A standard radioactive chromium (51Cr) release assay was used to assess the in vitro phagocytosis and lysis of bovine erythrocytes by cultured splenic, bone marrow and peripheral blood monocyte-derived (PBM) macrophages isolated from healthy and Trypanosoma congolense and T. vivax-infected cattle of the Boran and N'Dama breeds. Recombinant cytokines (rHuTNF-alpha and rBolFN-gamma) and non-acid dialysed peripheral blood mononuclear cell (PBMNC) culture supernatants stimulated these PBM for enhanced activities. The stimulants caused increases in the rate of erythrocyte phagocytosis and lysis by cultured PBM in a concentration dependent manner. But very high stimulant concentrations caused deceased in vitro erythrophagocytosis. However, bacterial lipopolysaccharide (LPS) and acid dialysed PBMNC culture supernatants did not cause any increase in cultured PBM erythrophagocytosis. In vitro erythrocyte phagocytosis and lysis by splenic, bone marrow and peripheral blood monocyte (PBM)-derived macrophages of Boran breed of cattle infected with Trypanosoma congolense increased from 14 days post-infection (DPI) onwards and thereafter maintained at various levels above pre-infection. Cultured splenic macrophages showed the greatest erythrocyte destruction capability while PBM-derived macrophages was the least. The rates of in vitro erythrocyte phagocytosis and lysis were higher with the cultured PBM of the Boran than those of the N'Dama cattle during T. congolense infection. The rate of in vitro erythrocyte destruction was however, similar in both groups of cattle during T. vivax infection. These results correlated positively with the dynamics and degree of anaemia developed by these groups of animals during both T. congolense and T. vivax infections. Cattle infected with T. congolense and T. vivax developed varying degrees of normocytic normochromic anaemia during infection. Boran cattle developed a more severe anaemia, and had to be treated with diminazine aceturate, than N'Dama cattle during T. congolense infection. Both breeds of cattle developed a milder but similar degree of anaemia during T. vivax infection. None of the animals were treated. The results of this study indicated a role of in vivo macrophage stimulatory factors, notably cytokines such as TNF-alpha and IFN-gamma in host's serum, as well as parasite antigens, which may act singly or in concert, in the process of enhanced erythrocyte destruction, hence anaemia by the mononuclear phagocytic system (MPS) during bovine trypanosomosis. PMID- 11206396 TI - Differential expression of surface membrane antigens on bovine monocytes activated with recombinant cytokines and during Trypanosoma congolense infection. AB - The expression of surface membrane antigens on peripheral blood monocytes (PBM) of cattle of the Boran and N'Dama breeds activated with recombinant cytokines (TNF-alpha and IFN-gamma) and during experimental infection with Trypanosoma congolense was investigated using monoclonal antibodies (MoAbs) and fluorescein activated cell sorter (FACS). The surface antigens investigated were C3bi receptor, major histocompartibility (MHC) II complex (Ia antigen) and two monocyte/macrophage (Mphi) differentiation antigens. The study revealed that both cytokines caused the enhancement of the expression of all the PBM surface antigens studied. rBolFN-gammaat low concentrations was more efficient in causing the activation of PBM. While the PBM of Boran cattle were more significantly activated to express the C3bi receptor vis-a-vis the Ia antigen than N'Dama cattle, the reverse was the case with the PBM of N'Dama cattle which expressed more Ia antigens than Boran PBM. Similar results were observed during T. congolense infection in the two breeds of cattle. The significantly higher expression of C3bi receptor and correspondingly lower Ia antigen expression by the PBM of Boran cattle, both during trypanosomosis and in vitro may be responsible for the higher rate of erythrocyte phagocytosis, hence the development of more severe anaemia by Boran cattle during trypanosomosis than N'Dama. In addition, the expression of significantly higher numbers of Ia antigen by N'Dama Mphi, hence are more able to process, present and initiate better trypanosome antigen-specific immune response than Boran cattle during infection. These two attributes are known genetic characteristics of trypanotolerance in cattle. PMID- 11206397 TI - Bacterial colonization and endotoxin activity during experimental acute fowl typhoid in chickens. AB - Bacterial colonization and endotoxin production were investigated before and after experimental Salmonella gallinarum infection in 8-week-old female broiler chickens. These parameters were assayed by means of colony forming units test (CFU) and the Limulus Amebocyte Lysate test (LAL), respectively. Birds were infected per os with 1,5 x 10(9) CFU/ml of wild strain of S. gallinarum isolated from a dead hen. Approximately 1,5 x 10(2); 1,3 x 10(2) and 1,2 x 10(2) CFU of S. gallinarum were recorded from 1 g of liver, 1 g of spleen and 1 ml of blood from the chickens on day 1 post infection. By day 4 corresponding data were 3,7 x 10(4); 4,8 x 10(3) and 1,1 x 10(3) respectively and on day 7 10(5) CFU were present in all three specimen types. The liver and spleen of dead birds were contaminated with more than 10(7) CFU per g. The endotoxin from S. gallinarum was found to have an activity of 1,5; 12,0 and 15,0 endotoxin units (EU)/ml on day 1, 4 and 7 after infection, respectively. No endotoxin activity was established in the blood of the control group (before infection) by the LAL test. This is the first time the connection between the amount of live S. gallinarum in the blood, liver and the circulating level of endotoxin in the blood during the infectious stage of experimental acute fowl typhoid, has been demonstrated. PMID- 11206398 TI - Pasteurella gallinarum: Zimbabwean experience of a versatile pathogen. AB - Pasteurella gallinarum-related outbreaks in chickens and African guinea fowls are described. Four outbreaks were recorded in chickens and one in guinea fowls. Periorbital swelling and keratoconjunctivitis were the consistently present clinical signs in all the diseased birds. In several, swollen hocks and wattles were also discerened. Birds which succumbed to the infection showed petechiation in the internal organs and evidence of airsacculitis. Pasteurella gallinarum was isolated from the lesions and also from conjunctival swabs of the apparently healthy in-contact birds. There was no evidence of concurrent infection with Haemophilus, Mycoplasma or Chlamydia. Quinolone therapy when resorted to on one of the farms resolved the clinical signs. Phenotypes of 28 isolates were studied. The results compared well with the Pasteurella gallinarum isolates reported earlier from elsewhere. It was also found that results of xylose fermentation and ONPG test appear to be a variable character. There is no earlier report of P. gallinarum infection in guinea fowls. PMID- 11206399 TI - Finally we have arrived in a new millennium. PMID- 11206400 TI - Paraoxonase2 polymorphisms are associated with nephropathy in Type II diabetes. AB - AIMS/HYPOTHESIS: Paraoxonase is a member of a multigene family of three genes. Paraoxonase2 gene polymorphisms have been associated with coronary heart disease in non-diabetic patients and with an increased fasting glycaemia in patients with Type II (non-insulin-dependent) diabetes mellitus. We tested the hypothesis of whether paraoxonase1 and paraoxonase2 polymorphisms were associated with diabetic nephropathy. METHODS: Our case-control study of 299 Swiss patients with Type II diabetes included 147 patients with confirmed diabetic nephropathy. RESULTS: In univariate analyses the two paraoxonase2 polymorphisms were associated with diabetic nephropathy. When subjected to multivariate analyses, both paraoxonase2 polymorphisms remained statistically associated with diabetic nephropathy independent of traditional risk factors (paraoxonase2-148: OR = 2.53, p = 0.003; paraoxonase2-311: OR = 2.67, p = 0.002). In addition, BMI interacted with paraoxonase2 polymorphisms as a risk factor of nephropathy. CONCLUSIONS/INTERPRETATION: The paraoxonase2 gene polymorphisms were significantly associated with diabetic nephropathy independent of traditional risk factors in Type II diabetic patients. The susceptibility to diabetic nephropathy was intensified by the degree of obesity. Pathophysiological pathways should be investigated and could be involved in insulin resistance or lipids metabolism or both. PMID- 11206401 TI - Renoprotective effects of a novel inhibitor of advanced glycation. AB - AIMS/HYPOTHESIS: ALT-946, an inhibitor of advanced glycation with a minimal inhibitory effect on nitric oxide synthase, was compared with aminoguanidine in experimental diabetic nephropathy. METHODS: In vitro and in vivo assays were used to assess the ability of ALT-946 to inhibit AGE-protein cross-link formation. Diabetic animals were randomly allocated into groups receiving aminoguanidine for 32 weeks, ALT-946 or vehicle (untreated). As a delayed intervention protocol, an additional diabetic group was treated with ALT-946 from week 16 to week 32 of the study. Non-diabetic rats were studied concurrently. Systolic blood pressure, body weight, plasma glucose, glycated haemoglobin and urinary albumin excretion were measured serially. Accumulation of advanced-glycation end products in the kidney was assessed by immunohistochemistry. RESULTS: The ALT-946 inhibitor was more potent than aminoguanidine in inhibiting AGE-protein cross-linking both in vitro and in vivo. Increased albuminuria observed in diabetic rats was attenuated in all three treatment groups. We found no difference in body weight, blood pressure or glycaemic control with any of the treatments. The untreated diabetic group had a twofold increase in glomerular staining for advanced-glycation end products compared with the diabetic groups which received treatment. CONCLUSION/INTERPRETATION: ALT-946 is a potent inhibitor of advanced renal glycation end-product accumulation and reproduces the renoprotective effects of aminoguanidine. Therefore, ALT-946 should be considered as a treatment for preventing or retarding diabetic nephropathy. PMID- 11206402 TI - Genetic and environmental nature of the insulin resistance syndrome in Indo Mauritian subjects with premature coronary heart disease: contribution of beta3 adrenoreceptor gene polymorphism and beta blockers on triglyceride and HDL concentrations. AB - AIMS/HYPOTHESIS: Insulin resistance syndrome is an important risk factor for developing premature coronary heart disease. It is a complex syndrome which could arise from the interaction of several genes modulated by environmental factors. The Trp64Arg polymorphism in the beta3-adrenoreceptor gene has been found to be associated with insulin resistance, obesity or with earlier onset of Type II (non insulin-dependent) diabetes mellitus in different populations. We aimed to study whether features of the insulin resistance syndrome are associated with this polymorphism in Indo-Mauritian patients with premature coronary heart disease. METHODS: We carried out a case control study using PCR-RFLP techniques, of consecutive Indo-Mauritian patients (n = 338) with premature coronary heart disease (onset below age of 60 years) and unrelated control subjects (n = 148) of the same ethnicity. RESULTS: In Indo-Mauritian patients with premature coronary heart disease who were not treated by beta blockers, triglyceride concentrations were lower (median: 1.44 vs 1.93 mmol/l, p < 0.008) and HDL cholesterol concentrations higher (mean: 0.98 vs 0.85 mmol/l, p < 0.015) in those carrying the wild type of the beta3-adrenoreceptor gene than in those carrying the Trp64Arg variant. The latter genotype specific effect on HDL was inverse in patients treated with beta blockers. CONCLUSION/INTERPRETATION: The beta3 adrenoreceptor gene variant seems to modulate the effects of beta blockers on triglyceride and HDL cholesterol concentrations in this group of Indo-Mauritian population. Dyslipidaemia, a key component of the metabolic syndrome has a heterogeneous nature in Indo-Mauritian subjects. This potent risk factor for early-onset coronary heart disease is influenced by the interaction between genetic and environmental effects. PMID- 11206403 TI - Polymorphisms in the neurogenin 3 gene (NEUROG) and their relation to altered insulin secretion and diabetes in the Danish Caucasian population. AB - AIM/HYPOTHESIS. Neurogenin 3 (NEUROG3) is a member of the subfamily of basic helix-loop-helix (bHLH) transcription factors involved in differentiation of the endocrine pancreas and therefore a possible candidate gene for maturity-onset diabetes of the young (MODY) and Type II (non-insulin-dependent) diabetes mellitus. METHODS: Using Polymerase-chain-reaction single-stranded-conformation polymorphism, we examined the coding region including the 5'-untranslated and 3'- untranslated regions of the NEUROG3 in a group of 133 diabetic patients comprising 19 MODY patients, 19 patients with dominant Type I diabetes, and 31 early-onset and 64 late-onset Type II diabetic patients. RESULTS: We found two missense mutations, Glyl67Arg and Serl99Phe, as well as two non-coding variants in the 5' UTR, a c --> t nucleotide variant at position -10 upstream of the start codon in one MODY patient and a 2 base pair (CA) deletion polymorphism at position -44/-45. Allele frequencies measured in 377 diabetic patients and in 217 glucose-tolerant control subjects were: Gly167Arg, 0.04 (95 % CI: 0.02-0.06) and 0.04 (0.02-0.06); Ser199Phe, 0.31 (0.26-0.36) and 0.30 (0.24-0.36); -44-45delCA, 0.33 (0.31-0.35) and 0.35 (0.32-0.38), respectively. Both Ser199Phe and the -44 45delCA were in linkage disequilibrium (chi2 > 60) but the Ser199Phe and the -44 45delCA polymorphism were not associated with consistent changes in fasting- or glucose-induced insulin secretion in 249 glucose-tolerant offspring (first-degree relatives) of Type II diabetic parents or in 217 unrelated middle-aged glucose tolerant subjects. CONCLUSION/INTERPRETATION: Genetic variability in NEUROG3 is not associated with dominant Type I diabetes, MODY, Type II diabetes or changes in insulin secretion in the Danish Caucasians examined subjects. PMID- 11206404 TI - Mutations in the hepatocyte nuclear factor-1beta (MODY5) gene are not a major factor contributing to end-stage renal disease in Japanese people with diabetes mellitus. PMID- 11206405 TI - A comparison of the prevalence of islet autoantibodies in children from two countries with differing incidence of diabetes. AB - AIMS/HYPOTHESIS: To examine the prevalence of sub-: clinical islet autoimmunity in children from two countries with a twofold to threefold difference in incidence of childhood Type I (insulin-dependent) diabetes mellitus. METHODS: Sera were collected from 2,860 English and 3,053 Lithuanian non-diabetic schoolchildren according to the same protocol. Occult diabetes was excluded by blood glucose measurement. Antibodies to GAD and the protein tyrosine phosphatase IA-2 were measured with standardised radiobinding assays in a single laboratory. Islet cell antibodies and insulin autoantibodies were additionally measured in all samples with GAD and/or IA-2 antibody levels above the 97.5th centile of the English schoolchildren. RESULTS: Of Lithuanian schoolchildren 2.7 % had GAD antibodies above the 97.5th centile of the English schoolchildren but only 0.2 % had antibodies to IA-2 above this threshold (p < 0.001). Islet cell and/ or insulin autoantibodies above the 97.5th centile were found in 22 Lithuanian and 16 English schoolchildren and the overall prevalence of two or more antibodies on or above the 97.5th centile was similar [0.7 % (0.5-1.1) vs 0.6 % (0.4-1.0)] in the two cohorts. CONCLUSION/INTERPRETATION: The prevalence of multiple antibody markers was similar in the cohorts from the two populations, despite the two to three-fold difference in incidence of diabetes. The unexpectedly high prevalence of subclinical islet autoimmunity suggests that the incidence of diabetes in Lithuania is likely to increase in the near future. PMID- 11206406 TI - Increasing trend of type I diabetes in children and young adults in the province of Turin (Italy). Analysis of age, period and birth cohort effects from 1984 to 1996. AB - AIMS/HYPOTHESIS: This study aimed to determine if the incidence of Type I (insulin-dependent) diabetes mellitus increased over time and if the time trend is attributable to linear trend, calendar period or birth cohort effects. METHODS: This study was based on a cohort of subjects aged 0-29 years from 1984 to 1996, who resided in the province of Turin, Italy. Poisson regression models were used to estimate the effect of sex, age, calendar time and cohorts on incidence rates. RESULTS: The mean incidence rate in the age group of 0 to 29 years was 7.78 of 100,000 person-years (95% confidence interval: 7.26-8.32), with a lower risk in women than in men [rate ratio (RR): 0.76 (0.67-0.88)]. We found a trend of incidence increasing over time (annual increase of risk 2.25 % a year, 95 % CI 0.44-4.10). In Poisson regression analysis we found that the best model was the one with sex, age and a linear term attributable to either calendar period or cohort effects. The linear term corresponds to a RR of 1.12 (1.02 1.22,p = 0.015) for each 5-year age span. CONCLUSION/INTERPRETATION: We found that the time trend in this Mediterranean area was similar in magnitude to that reported in northern European countries. The increase was linear in pattern, each birth cohort and each calendar period showing a higher risk than the preceeding one with some evidence of two steep increases in the incidence of Type I diabetes centered on the years 1964 and 1984. We found that the incidence of diabetes increased in the 0 to 14 age group and also in the older age group of 15 to 29 years and that the age-period models were not statistically significantly better than the age-cohort models. PMID- 11206407 TI - Diabetic groups as defined by ADA and NDDG criteria have a similar aerobic capacity, blood pressure and body composition. American Diabetes Association and National Diabetes Data Group. AB - AIMS/HYPOTHESIS: In 1997 the American Diabetes Association (ADA) published new categories for diabetes based on fasting plasma glucose that classified diabetes as a plasma glucose of 7.0 mmol/l, or more, rather than one of 7.8 mmol/l or more, as published previously by the National Diabetes Data Group (NDDG) in 1979. We compared the cardiovascular disease risk factors of subjects classified as having Type II (non-insulin-dependent) diabetes mellitus under the NDDG and ADA criteria. METHODS: We examined a database of approximately 3,700 men (40.4 +/- 11.5 years old) and distributed them into four categories: normal fasting plasma glucose (NFG) of less than 6.1 mmol/l, impaired (IFG) 6.1 to 7.0 mmol/l, ADA diabetic 7.0 to 7.8 mmol/l and NDDG diabetic of 7.8 mmol/l or more. RESULTS: Fasting glucose was 5.2 +/- 0.5, 6.4 +/- 0.2, 7.3 +/- 0.2 and 11.2 +/- 2.9 mmol/l for the subjects of the NFG, IFG, ADA and NDDG groups, respectively. Estimated treadmill VO2max was 41.4 +/- 8.0, 36.0 +/- 7.8, 32.2 +/- 7.6, 30.6 +/- 7.0 ml x kg(-1) x min(-1) in the NFG, IFG, ADA, and NDDG groups, respectively (NFG and IFG > ADA and NDDG: p < 0.05). The ADA and NDDG groups were also similar for resting and exercise blood pressure and body composition. Triglycerides and total: HDL cholesterol ratios were higher and LDL cholesterol concentration was lower, in the NDDG group than in all other groups (p < 0.05). Total and LDL cholesterol in the ADA and NDDG groups were similar. CONCLUSION/INTERPRETATION: The similarities in the aerobic capacities, blood pressure and body composition of the ADA and NDDG groups indicate that the decision to lower the cut-off from 7.8 mmol/l to 7.0 mmol/l blood glucose for the clinical classification of diabetes was appropriate. The ADA and NDDG groups, however, might not have identical risks for cardiovascular disease because of differences between total:HDL cholesterol ratios, circulating HDL cholesterol and triglyceride concentrations. PMID- 11206408 TI - Diabetes and gender. AB - It is often assumed that there is little or no sex bias within either Type I (insulin-dependent) or Type II (non-insulin-dependent) diabetes mellitus. This review considers evidence that sex effects of interest and importance are present in both forms of the disease. Type I diabetes is the only major organ-specific autoimmune disorder not to show a strong female bias. The overall sex ratio is roughly equal in children diagnosed under the age of 15 but while populations with the highest incidence all show male excess, the lowest risk populations studied, mostly of non-European origin, characteristically show a female bias. In contrast, male excess is a consistent finding in populations of European origin aged 15-40 years, with an approximate 3:2 male:female ratio. This ratio has remained constant in young adults over two or three generations in some populations. Further, fathers with Type I diabetes are more likely than affected mothers to transmit the condition to their offspring. Women of childbearing age are therefore less likely to develop Type I diabetes, and--should this occur--are less likely to transmit it to their offspring. Type II diabetes showed a pronounced female excess in the first half of the last century but is now equally prevalent among men and women in most populations, with some evidence of male preponderance in early middle age. Men seem more susceptible than women to the consequences of indolence and obesity, possibly due to differences in insulin sensitivity and regional fat deposition. Women are, however, more likely to transmit Type II diabetes to their offspring. Understanding these experiments of nature might suggest ways of influencing the early course of both forms of the disease. PMID- 11206409 TI - Testing the fetal origins hypothesis in twins: the Birmingham twin study. AB - AIMS/HYPOTHESIS: To test whether the link between birthsize and raised blood pressure or glucose tolerance is due to genetic or intrauterine factors, we studied whether differences in birthweight between pairs of monozygous and dizygous twins are associated with adult differences in blood pressure and glucose tolerance. METHODS: A sample of 58 monozygous and 140 dizygous twins were identified from a register of births in Birmingham, United Kingdom, between 1950 and 1954. The twins had their blood pressure measured and underwent an oral glucose tolerance test. RESULTS: There were no statistically significant associations between birthweight, length or ponderal index, and either blood pressure or glucose tolerance in the twins. Although there were substantial within-pair differences in birthweight between monozygous and dizygous twin pairs, these differences did not correlate with the adult outcomes. Monozygous correlations, however, for both blood pressure and glucose tolerance were statistically significantly higher than dizygous correlations and a quantitative genetic model suggested statistically significant heritability for these traits. In contrast correlations of birthsize were similar in monozygous and dizygous pairs suggesting only a small genetic component in determining fetal size. CONCLUSION/INTERPRETATION: Our results show that birthsize in twins does not predict adult blood pressure or glucose tolerance. We also suggest that shared genetic determinants for fetal growth and adult outcomes are not likely to be prevalent or powerful. PMID- 11206410 TI - Male-to-female excess in diabetes diagnosed in early adulthood is not specific for the immune-mediated form nor is it HLA-DQ restricted: possible relation to increased body mass index. AB - AIMS/HYPOTHESIS. We investigated whether the reported HLA-DQ/DR restricted male to-female (M:F) excess in Type I (insulin-dependent) diabetes mellitus also exists in Belgian patients, is specific for immune-mediated diabetes, remains genotype-restricted after adjustment for age at diagnosis, and is associated with sex-dependent environmental factors. METHODS: Autoantibodies, HLA-DQ and 5'INS (5'insulin gene) polymorphisms were assessed in 2,532 diabetic patients (all phenotypes) diagnosed under 40 years of age. Autoantibodies and body mass index (expressed as a standard deviation score by comparison to age-matched and sex matched control subjects; SDS-BMI) were measured in 1986 siblings or offspring of Type I diabetes patients (0-39 years). RESULTS: In patients aged 15-39 years at diagnosis, the male-to-female ratio was 1.5 or more regardless of their antibody status and significantly higher (p < 0.001) than that in the age-matched Belgian general population. There was no sex bias in patients under 15 years of age. Overall, the male-to-female ratio was significantly higher in patients without HLADQA1*0301-DQB1*0302 (p < or = 0.003) but stratification in age groups and multivariate analysis identified age as the major determinant of male-to-female ratio. The SDS-BMI increased (p < 0.01) in male antibodypositive relatives (n = 103) but not in female antibody-positive (n = 92) or in antibody-negative relatives (n = 1,791). This phenomenon tended to be restricted to male relatives who were positive only for glutamate decarboxylase antibodies (n = 44). CONCLUSIONS/INTERPRETATION: The male-to-female excess in Belgian diabetic patients diagnosed in early adulthood is not specific for immune-mediated Type I diabetes and not HLA-DQ or 5'INS restricted. Our data suggest that, similar to Type II (non-insulin-dependent) diabetes mellitus, the metabolic burden of obesity and insulin resistance could preferentially precipitate postpubertal clinical onset in male subjects with slowly progressive subclinical (immune mediated) diabetes. PMID- 11206411 TI - Lipid-dependent control of hepatic glycogen stores in healthy humans. AB - AIMS/HYPOTHESIS: Non-esterified fatty acids and glycerol could stimulate gluconeogenesis and also contribute to regulating hepatic glycogen stores. We examined their effect on liver glycogen breakdown in humans. METHODS: After an overnight fast healthy subjects participated in three protocols with lipid/heparin (plasma non-esterified fatty acids: 2.2 +/- 0.1 mol/l; plasma glycerol: 0.5 +/- 0.03 mol/l; n = 7), glycerol (0.4 +/- 0.1 mol/l; 1.5 +/- 0.2 mol/l; n = 5) and saline infusion (control; 0.5 +/- 0.1 mol/l; 0.2 +/- 0.02 mol/l; n = 7). Net rates of glycogen breakdown were calculated from the decrease of liver glycogen within 9 h using 13C nuclear magnetic resonance spectroscopy. Endogenous glucose production was measured with infusion of D-[6,6-2H2]glucose. RESULTS: Endogenous glucose production decreased by about 25 % during lipid and saline infusion (p < 0.005) but not during glycerol infusion (p < 0.001 vs lipid, saline). An increase of plasma non-esterified fatty acids or glycerol reduced the net glycogen breakdown by about 84 % to 0.6 +/- 0.3 micromol x kg(-1) x min(-1) (p < 0.001 vs saline: 3.7 +/- 0.5 micromol x kg(-1) x min(-1)) and by about 46 % to 2.0 +/- 0.4 micromol x kg(-1) x min(-1) (p < 0.01 vs saline and lipid), respectively. Rates of gluconeogenesis increased to 11.5 +/- 0.8 micromol x kg( 1) x min(-1) (p < 0.01) and 12.8 +/- 1.0 micromol x kg(-1) min(-1) (p < 0.01 vs saline: 8.2 +/- 0.7 micromol x l(-1) x min(-1)), respectively. CONCLUSION/INTERPRETATION: An increase of non-esterifled fatty acid leads to a pronounced inhibition of net hepatic glycogen breakdown and increases gluconeogenesis whereas glucose production does not differ from the control condition. We suggest that this effect is not due to increased availability of glycerol alone but rather to lipid-dependent control of hepatic glycogen stores. PMID- 11206412 TI - Distinct long-term regulation of glycerol and non-esterified fatty acid release by insulin and TNF-alpha in 3T3-L1 adipocytes. AB - AIMS/HYPOTHESIS: Adipose tissue lipolysis plays a central part in total body fuel metabolism. Our study was to assess the long-term regulation of glycerol and non esterified fatty acid (NEFA) release by insulin or TNF-alpha. METHODS: Fully differentiated 3T3-L1 adipocytes were exposed for up to 22 h to insulin or TNF alpha. RESULTS: Long-term insulin treatment resulted in increased basal glycerol release, reaching sixfold at 22 h with 1 nmol/l insulin. Partial inhibition was observed by pharmacologically inhibiting phosphatidylinositol 3-kinase or the mitogen-activated kinase kinase--extracellular signal-regulated kinase cascades. This represented 50-60% of the response induced by 1 nmol/l TNF-alpha and approximately 40 % of the glycerol release maximally stimulated by isoproterenol (1 micromol/l, 30 min). The cellular mechanism seemed to be distinct from that of TNF-alpha: First, glycerol release in response to long-term insulin was progressive with time and did not display a lag-time characteristic of the effect of TNF-alpha. Second, pretreatment and co-treatment of the cells with troglitazone greatly inhibited TNF-alpha-induced glycerol release (128.5 +/- 10.2 to 35.4 +/- 2.1 nmol/mg protein per h) but not the effect of insulin, which was exaggerated. Third, hormone-sensitive lipase protein content was decreased (45 %) by TNF-alpha but not following long-term insulin. Finally, TNF-alpha was associated with NEFA release to the medium, whereas long-term insulin treatment was not. Moreover, glycerol release during isoproterenol-stimulated lipolysis was additive to the effect of long-term insulin, whereas NEFA release was inhibited by nearly 90 %. CONCLUSIONS INTERPRETATION: Contradictory to its short-term inhibitory effect, long-term insulin stimulates glycerol release with concomitant stimulation of NEFA re-esterification. PMID- 11206413 TI - Short-term exclusive breastfeeding predisposes young children with increased genetic risk of Type I diabetes to progressive beta-cell autoimmunity. AB - AIMS/HYPOTHESIS: This study aimed to establish the relation between early infant nutrition and signs of beta-cell autoimmunity in young children. METHODS: We identified and observed from birth 2949 infants with increased genetic risk of Type I (insulin-dependent) diabetes mellitus (HLA DQB1*02/ *0302 or DQB1*0302/x, x = other than *02, *0301 or *0602) and monitored them for islet cell antibodies at 3 to 6 month intervals. If an infant seroconverted to islet cell antibody positivity, all of his or her samples were also analysed for autoantibodies to insulin, GAD65 (GADA) and to the protein tyrosine phosphatase related IA-2 molecule (IA-2A). Our case-control study comprises the first 65 children who seroconverted to islet cell antibody positivity before the age of 4 years and 390 control children who were islet cell antibody-negative (six control children/ case). We monitored the duration of exclusive and total breastfeeding and the age at which cows' milk was introduced. RESULTS: Infants who had been breastfed exclusively for at least 4 months had lower risk of seroconversion to positivity for IA-2A or all four autoantibodies [odds ratio (OR) 0.24; 95 % CI 0.06-0.94 and OR 0.17; 95 % CI 0.03-0.86, respectively] than those infants who had been breastfed exclusively for less than 2 months. The risk of seroconversion to positivity for IA-2A or all four autoantibodies was higher in those younger than 2 months (OR 4.37; 95 % CI 1.33-14.42 and OR 5.02; 95 % CI 1.27-19.89) or aged 2 to 3.9 months (OR 5.50; 95 % CI 1.21-25.04 and 6.19; 95% CI 1.10-34.84) when they first received cows' milk than in those aged 4 months or older. CONCLUSIONS/INTERPRETATION: These observations suggest that short-term breastfeeding and the early introduction of cows' milk-based infant formula predispose young children who are genetically susceptible to Type I diabetes to progressive signs of beta-cell autoimmunity. PMID- 11206414 TI - HLA-DR53 molecules restrict glutamic acid decarboxylase peptide presentation to T cells of a Type I diabetes patient: specification of the trimolecular HLA peptide/T-cell receptor complex. AB - AIMS/HYPOTHESIS: Our aim was to define the molecular specificity of glutamic acid decarboxylase-specific T-cells isolated from a patient (patient 40) with recent onset Type I (insulin-depent) diabetes mellitus. METHODS: The peptide epitope was defined using synthetic peptides to identify the minimal sequence required for T cell activation and to determine the amino acids that contribute either to MHC binding or T-cell receptor signaling. The MHC class II-restricted peptide presentation was determined using a panel of allogeneic antigen-presenting cells and murine fibroblast-cell lines transfected to express individual human class II alleles and by blocking studies with monoclonal antibodies. The T-cell receptor was also molecularly characterized. RESULTS: Despite that patient 40 carries high risk alleles of the DRB1 and DQB1 loci, his T-cells recognize a glutamic acid decarboxylase-derived peptide in association with class II, DR53, molecules. Although anchor residues for DR53 molecules have not yet been determined, it was possible to model epitope binding based on sequence comparisons with other class II molecules associated with susceptibility or protection for Type I diabetes. CONCLUSION/INTERPRETATION: The complete molecular specification of the MHC peptide ligand and the T-cell receptor complex of glutamic acid decarboxylase specific T-cells will enable analysis of strategies designed to alter T-cell function. For example, the role of altered peptide ligands or T-cell receptor specific peptides can be studied using a model whose components reflect the natural affinities of MHC-peptide and T-cell receptor-ligand interactions selected in response to this important autoantigen. PMID- 11206415 TI - The IA-2 gene family: homologs in Caenorhabditis elegans, Drosophila and zebrafish. AB - AIMS/HYPOTHESIS: IA-2 and IA-2beta are major autoantigens in Type I (insulin dependent) diabetes mellitus and are expressed in neuroendocrine tissues including the brain and pancreatic islets of Langerhans. Based on sequence analysis, IA-2 and IA-2beta are transmembrane protein tyrosine phosphatases but lack phosphatase activity because of critical amino acid substitutions in the catalytic domain. We studied the evolutionary conservation of IA-2 and IA-2beta genes and searched for homologs in non-mammalian vertebrates and invertebrates. METHODS: IA-2 from various species was identified from EST sequences or cloned from cDNA libraries or both. Expression in tissues was determined by transfection and in situ hybridization. RESULTS: We identified homologs of IA-2 in C. elegans, Drosophila, and zebrafish which showed 46, 58 and 82 % identity and 60, 65 and 87 % similarity, respectively, to the amino acids of the intracellular domain of human IA-2. Further studies showed that IA-2 was expressed in the neural tissues of the three species. Comparison of the genomic structure of the intracellular domain of human IA-2 with that of human IA-2beta showed that they were nearly identical and comparison of the intron-exon boundaries of Drosophila IA-2 with human IA-2 and IA-2beta showed a high degree of relatedness. CONCLUSION/INTERPRETATION: Based on these findings and sequence analysis of IA-2 homologs in mammals, we conclude that there is an IA-2 gene family which is a part of the larger protein tyrosine phosphatase superfamily. The IA-2 and IA 2beta genes represent two distinct subgroups within the IA-2 family which originated over 500 million years ago, long before the development of the pancreatic islets of Langerhans. PMID- 11206416 TI - Adenine and guanine nucleotide-specific succinyl-CoA synthetases in the clonal beta-cell mitochondria: implications in the beta-cell high-energy phosphate metabolism in relation to physiological insulin secretion. AB - AIMS/HYPOTHESIS: Succinyl-CoA synthetase catalyses the substrate level phosphorylation of ADP or GDP. It also supplies succinyl-CoA for heme synthesis. Recently, two distinct mitochondrial succinyl-CoA synthetase activities, one specific for ATP and the other for GTP, have been characterized in various tissues of pigeon. Because of the relative importance of mitochondrial high energy phosphate metabolism in physiological insulin secretion and the few data available on mitochondrial succinyl-CoA synthetase in the beta cell, this study examined whether ATP-specific and GTP-specific succinyl-CoA synthetase activities are localized in the clonal beta-cell mitochondria. METHODS: Using the mitochondrial extracts from clonal beta [INS-1 and HIT-T15] cells, we measured the formation of succinyl-CoA from succinate, CoA and ATP or GTP. To confirm the identity of these two enzymes, individual subunits of ATP-specific and GTP specific to succinyl-CoA synthetase were identified by Western blot analysis. RESULTS: Both ATP-and GTP activities of succinylCoA synthetase were observed in the mitochondrial fractions from these cells. The ratios of GTP to ATP activities of succinyl-CoA synthetase were near unity in both of the cell types studied. Using affinity-purified antisera directed specifically against individual (alpha and beta) subunits of succinyl-CoA synthetase, we also identified both ATP specific and GTP-specific forms of succinyl-CoA synthetase in HIT and INS cell mitochondria. Furthermore, using [gamma-32P]ATP as a phosphoryl donor, we observed that the alpha subunit of succinyl-CoA synthetase undergoes autophosphorylation at a histidine residue; co-provision of exogenous succinate and CoA resulted in pronounced dephosphorylation of the phosphorylated alpha subunit of succinyl-CoA synthetase. CONCLUSION/INTERPRETATION: We provide evidence for the localization of two distinct activities of succinyl-CoA synthetase in the beta cell mitochondria. Whereas it is well established that ATP is critical for the beta cell mitochondrial metabolism, we propose that GTP generated by the activation of succinylCoA synthetase could promote key functional roles in the mitochondrial metabolism leading to insulin secretion. PMID- 11206417 TI - Glucose and insulin exert additive ocular and renal vasodilator effects on healthy humans. AB - AIMS/HYPOTHESIS: There is evidence that insulin and glucose cause renal and ocular vasodilation. There is, however, currently no data on the effect of combined hyperglycaemia and hyperinsulinaemia on the renal and ocular blood flow seen in diabetic patients on insulin therapy. METHODS: We carried out two different 3-way crossover studies in healthy subjects (each, n = 9). In study one, hyperglycaemic clamps (5.6 mmol/l, 11.1 mmol/ 1, 16.7 mmol/l) were carried out during placebo or insulin (dose 1: 1 mU/kg/min; dose 2: 2 mU/kg/min) infusion. The second study was identical but endogenous insulin secretion was blocked with somatostatin. The renal plasma flow, glomerular filtration rate and pulsatile choroidal blood flow were measured using the paraaminohippurate method, the inulin method and a laser interferometric measurement of fundus pulsation amplitude, respectively. RESULTS: Insulin increased renal plasma flow and fundus pulsation amplitude but not the glomerular filtration rate. Hyperglycaemia increased all the renal and ocular parameters studied. Haemodynamic effects of glucose and insulin were additive when somatostatin was co-administered but not under basal conditions. CONCLUSIONS/INTERPRETATION: Glucose and insulin can exert additive vasodilator properties on renal and ocular circulation. To find out whether this observation is related to the increased regional perfusion in diabetes longitudinal studies on patients with Type I (insulin-dependent) diabetes mellitus are needed. PMID- 11206418 TI - Heterosexuals' use of "fag" and "queer" to deride one another: a contributor to heterosexism and stigma. AB - This paper is on heterosexuals' use of words such as "fag" and "queer" to refer to one another in an insulting manner. This behavior perpetuates heterosexism and the stigmatization of gays. Two hundred and fifty-seven university students (73% Euro-American) served as participants. Males exhibited more anti-gay prejudice and anti-gay behavior than females. Heterosexual males frequently used words such as "fag" and "queer" to put one another down. Anti-homosexual prejudice was predictive of anti-gay behavior. However, approximately half of those who engaged in the behavior were not strongly anti-homosexual. For these individuals, the behavior may win approval from their social group. Awareness campaigns and peer reminders that the derisive use of "fag" and "queer" harms homosexuals may be effective in changing this group. It is more difficult to reduce this behavior in individuals with strong anti-homosexual attitudes. The role of individuals and educational and work organizations in bringing about change is discussed. PMID- 11206419 TI - Gay male adult development: some stage issues of an older cohort. AB - This paper is a qualitative investigation into developmental stage issues, using a sample of older gay males. Twenty Ohio informants were obtained through convenience sampling for unstructured oral interviews. Erik Erikson's developmental stage model serves as representing traditional stage theory. The traditional view portrays life course in heterosexual terms. While the developmental issues addressed across the life course are likely the same or similar, the traditional schedules of these issues are not apt for gays. Gay life paths start at different ages, based on when identity-acceptance begins. Only then can a gay person undertake successful adult development. Findings indicate that as closeted homosexuals, gay men may experience a false development, resulting from living a double-life. With the acceptance of one's homosexuality, developmental regression occurs in an effort to address gay identity issues previously denied or ignored. Many of the developmental issues arise not from being gay, per se, but from discovering how to assimilate being gay into one's life pattern. This paper thus shows an imperfection in traditional stage models. PMID- 11206420 TI - Heterosexual masculinity and homophobia: a reaction to the self? AB - Heterosexual masculinity is the cultural pressure exerted on males to be masculine in traits and heterosexual in orientation or else be viewed as feminine and socially unacceptable. The current study investigated the link between heterosexual masculinity and homophobia in 74 college males. Specifically, gender self-discrepancy (how well males think they fit cultural expectations of how they should act as a man), attribute importance (perceived importance of possessing masculine attributes), and self-esteem were examined as predictors of homophobia. Attribute importance, self-discrepancy along masculine traits, and their interaction significantly predicted degree of homophobia in this sample. PMID- 11206421 TI - The influence of race, ethnicity, class, and sexual politics on lesbians' body image. AB - Based on interviews conducted with eight lesbians, this paper explores how the intersection of gender, sexual identity, race, ethnicity, and class affect lesbians' feelings about their bodies. Their responses suggest that, while being female has a strong effect on lesbians' feelings about their bodies, issues of race, acculturation, and class also affect body image. Lesbian feminism and S/M politics also appear to play a significant role in lesbians' body image. These findings highlight the limitations of existing theories about body image and call for a more complex theory incorporating a more diverse range of experiences. PMID- 11206422 TI - The Toronto Lesbian Family Study. AB - Twenty-seven lesbian mothers completed standardized tools chosen to assess current functioning, followed by a video-taped interview. Verbal children were also interviewed. Questions involved perceptions of the mothers' and children's experiences of being homosexual or being raised by homosexual parents, knowledge and fantasies about the donor/father, feelings regarding the role of fathers, parents' experiences of being fathered, legal issues, and development. All mothers were strongly lesbian identified and most were completely "out." All but one mother planned to or had told their children. All mothers planned to reveal donor information at an appropriate age. Many, especially parents of boys, had concerns about lack of a male role model, but none felt this would negatively affect the child's development. Mothers were open to having their child ask questions and even seek out the donor when older. Thirty-one percent of mothers reported a positive relationship with their own father, 42% a father who was present but unavailable or punitive and 27% a completely absent father for large parts of their childhood. Couples divided parenting work based on individual strengths and interests, work schedules and demands. Only two of the couples felt that one of them played a role typical of a father. An aggregate score was compiled for each mother based on the number of negative outcomes in the standardized tools. The mean number of negative outcomes for the mothers was 3.15 (SD = 1.85). Of the six women with 5 or more negative outcomes on the scales, three were single parents and one had lost her partner when her child was two months old. On the CESD, three mothers showed depression levels that were high. The Internal External scale showed 42% of mothers to have an external locus of control. Three mothers scored negatively on the Family Assessment Device. Ninety two percent of women showed moderate to high self-esteem on the Rosenberg Self Esteem scale, and the Parenting Stress Index found only 4 women showing enough stress to warrant follow-up. Mothers who reported very negative early experiences of coming out were more likely to report current depressive symptoms (p = .03). All but one child living in two-mother homes identified both mothers as part of their family. Our initial impression is that these are primarily strong families with a variety of parenting skills, stressors and philosophies. PMID- 11206423 TI - Considerations of family structure and gender composition: the lesbian and gay stepfamily. AB - Lesbian and gay stepfamilies are unique family forms which must be investigated as such. This paper explores the similarities and dissimilarities between heterosexual stepfamilies and lesbian/gay stepfamilies, arguing that similarity of structure is impacted by gender composition. Utilizing face-to-face and telephone interviews with biological and stepparents in 23 lesbian and gay stepfamilies, the results show that while lesbian and gay stepfamilies share some challenges and strengths with heterosexual stepfamilies, they also evidence a unique and flexible adaptation to becoming a family. The paper is aimed at delineating future areas for lesbian and gay stepfamily research. PMID- 11206424 TI - Popular cinema and lesbian interpretive strategies. AB - In its examination of the relationship between popular film and lesbian viewing practices, this study attempts to more fully elucidate current ideas around audience engagement and forms of cultural reception. Drawing on 15 in-depth interviews conducted in Western Canada in 1996, the results clearly demonstrate the existence of active lesbian viewers, whose interpretations of popular film are intimately informed by lesbian-specific life experiences and cultural competencies. Although the social conditions which create the need for resistant viewing are themselves oppressive, subversion of mainstream film holds out some possibility of empowerment for lesbian viewers. PMID- 11206425 TI - Development of differentiation between writing and drawing systems. AB - When does a writing system emerge out of children's drawing to separate (a) script processing and production from (b) picture processing and production? And does one system's activation help or hinder the other system's operation? Children 4-12 years of age wrote repeated Os and Vs and drew matching shapes, in the contexts of script and of pictures. The technique elicits matching products in order to identify differences between production kinematics in different contexts. A transition occurred around age 6 in which (a) production was more fluent for writing than drawing and (b) activation of one system interfered with the other. Modeling the consolidation of both phenomena generated testable parameters for the slow approach to the adult steady state, involving increasing specialization and the waning of the need for suppression of the two systems' interference. PMID- 11206426 TI - Sibling influences on gender development in middle childhood and early adolescence: a longitudinal study. AB - The development of gender role qualities (attitudes, personality, leisure activities) from middle childhood to early adolescence was studied to determine whether siblings' gender role qualities predicted those of their sisters and brothers. Participants were 198 firstborn and second-born siblings (Ms = 10 years 9 months and 8 years 3 months, respectively, in Year 1) and their parents. Families were interviewed annually for 3 years. Firstborn siblings' qualities in Year 1 predicted second-born children's qualities in Year 3 when both parent and child qualities in Year 1 were controlled, a pattern consistent with a social learning model of sibling influence. Parental influence was more evident and sibling influence less evident in predicting firstborns' qualities; for firstborns, sibling influences suggested a de-identification process. PMID- 11206427 TI - Self-representations and socioemotional competence in young children: a 3-year longitudinal study. AB - In a longitudinal study, the connections between children's self-representations at age 5 and their self-perceptions, socioemotional competence according to the teacher, and peer acceptance at age 8 were examined. The sample consisted of 60 children (33 boys, 27 girls). Self-representations at age 5 were assessed by the Puppet Interview (J. Cassidy, 1988). Results generally revealed the expected connections between the positiveness of self at age 5 and self-perceptions and socioemotional functioning 3 years later. These findings support the predictive validity of the Puppet Interview. Moreover, they suggest that young children do possess at least a rudimentary sense of being generally worthy and lovable, which can be assessed by using adequate, age-appropriate interviews. PMID- 11206428 TI - Attention and recognition memory in the 1st year of life: a longitudinal study of preterm and full-term infants. AB - Several aspects of visual attention and their implications for recognition memory were examined in a longitudinal sample of full-term and preterm (birth weight < 1,750 g) infants seen at 5, 7, and 12 months of age. At all 3 ages, full-terms had shorter look durations, faster shift rates, less off-task behavior, and higher novelty scores than preterms. Both groups followed similar developmental trajectories, with older infants having shorter looks and more shifts. Infants were consistent in attentional style across problems of the same type, across problems that used different types of stimuli (faces and patterns), and across the familiarization and test phases of this paired-comparison design; there was also modest cross-age stability. Shorter looks and higher shift rates during familiarization were related to better recognition memory, with shift rate adding to prediction independently of either peak or mean look. These findings underscore the importance of attention to infant information processing. PMID- 11206429 TI - Young children's evaluations of exclusion in gender-stereotypic peer contexts. AB - This study investigated how 50 preschool children (25 girls, 25 boys) evaluated the appropriateness of excluding boys and girls from two types of activities (doll play, truck play) and two types of future roles (playing a teacher, playing a firefighter) across different exclusion contexts. Children judged straight forward exclusion from activities on the basis of gender as wrong, even if the child's gender was stereotypical of the activity. Furthermore, they justified these decisions on the basis of moral reasons, such as equality and unfairness. Children used a mixture of moral and social conventional reasoning (including stereotypes), however, to evaluate multifaceted situations that called for judgments about both inclusion and exclusion and that included information about the children's past experience with the activity. PMID- 11206430 TI - Early adolescent peer orientation and adjustment during high school. AB - The long-term consequences of early adolescents' orientation toward peers for their adjustment during high school were assessed. Approximately 1,200 adolescents completed questionnaires in the 7th grade and in the 10th or 12th grades; course grades were also obtained from the students' school records. Early adolescents who were willing to sacrifice their talents, school performance, and parents' rules engaged in greater problem behavior and evidenced lower academic achievement than did other adolescents during high school. The poorer adjustment of adolescents with this extreme orientation toward peers was mediated by their reported involvement in deviant peer groups. In contrast, a tendency to seek advice from peers more than from parents during early adolescence had little implication for later adjustment. Discussion focuses on the need to consider the role of peer dependence along with the effects of supportive friendships during adolescence. PMID- 11206431 TI - Maltreatment, competency deficits, and risk for academic and behavioral maladjustment. AB - Maltreatment was predicted to negatively affect children's academic and behavioral adjustment through the creation of deficits in academic engagement, social competencies, ego resiliency, and ego control. Teachers' comprehensive evaluations, school records, and camp counselors' ratings were obtained for 229 socioeconomically disadvantaged children (ages 5-12 years), 146 of whom had been maltreated. Maltreated children showed less academic engagement, more social skills deficits, and lower ego resiliency than nonmaltreated comparison children. Maltreated children manifested multiple forms of academic risk and showed more externalizing and internalizing behavior problems. The effects of maltreatment on academic maladjustment were partially mediated by academic engagement, whereas maltreatment's effects on behavior problems were mediated fully by social competencies and ego resiliency. PMID- 11206432 TI - In vitro fertilization and the family: quality of parenting, family functioning, and child psychosocial adjustment. AB - This study examined associations between homologous in vitro fertilization (IVF) and quality of parenting, family functioning, and emotional and behavioral adjustment of 3-7-year-old children. A cross-sectional survey was conducted in Taiwan with 54 IVF mother-child pairs and 59 mother-child pairs with children conceived naturally. IVF mothers reported a greater level of protectiveness toward their children than control mothers. Teachers, blind to condition, rated IVF mothers as displaying greater warmth but not overprotective or intrusive parenting behaviors toward their children. Teachers scored children of IVF as having fewer behavioral problems than control children. In contrast, IVF mothers reported less satisfaction with aspects of family functioning. Family composition moderated parenting stress: IVF mothers with only 1 child perceived less parenting stress than did those in the control group. PMID- 11206433 TI - Essentialism in Brazilian children's extensions of animal names. AB - The present study investigates whether Brazilian children have essentialist beliefs about animal categories. Two groups of Brazilian 4-year-olds (middle class and from shantytowns) were told that 2 animals share either internal or superficial properties. They were then taught labels for the animals. Across conditions, children from both groups were equally likely to interpret the labels as referring to mutually exclusive categories of animals, but they differed on how likely they were to maintain an inclusion relation between the labels. More important, children from both groups were more likely to accept a common label for animals sharing internal than superficial properties, indicating that internal property information convinced children that the animals were of the same kind. These findings were comparable to the results of a recent study by G. Diesendruck, S. A. Gelman, and K. Lebowitz (1998) with North American 4-year olds. PMID- 11206434 TI - Aggression toward female partners by at-risk young men: the contribution of male adolescent friendships. AB - Deviancy training was examined as a risk factor for physical and psychological aggression toward a female partner among boys and young men in the Oregon Youth Study. Hostile talk about women during videotaped male friendship interactions was hypothesized to indicate a process by which aggression toward women is reinforced within male peer networks. Both antisocial behavior and hostile talk were predicted to be associated with later aggression toward a female partner. Prospective developmental models were tested from 9-10 years of age through young adulthood. Findings indicated that the relation of deviant peer association in adolescence and later aggression toward a partner was mediated by antisocial behavior; observed hostile talk about women with male peers explained additional variance in aggression toward a partner. PMID- 11206435 TI - Absolute pitch in infant auditory learning: evidence for developmental reorganization. AB - To what extent do infants represent the absolute pitches of complex auditory stimuli? Two experiments with 8-month-old infants examined the use of absolute and relative pitch cues in a tone-sequence statistical learning task. The results suggest that, given unsegmented stimuli that do not conform to the rules of musical composition, infants are more likely to track patterns of absolute pitches than of relative pitches. A 3rd experiment tested adults with or without musical training on the same statistical learning tasks used in the infant experiments. Unlike the infants, adult listeners relied primarily on relative pitch cues. These results suggest a shift from an initial focus on absolute pitch to the eventual dominance of relative pitch, which, it is argued, is more useful for both music and speech processing. PMID- 11206436 TI - Child-parent attachment and children's peer relations: a quantitative review. AB - The central premise of attachment theory is that the security of the early child parent bond is reflected in the child's interpersonal relationships across the life span. This meta-analysis was based on 63 studies that reported correlations between child-parent attachment and children's peer relations. The overall effect size (ES) for child-mother attachment was in the small-to-moderate range and was quite homogeneous. ESs were similar in studies that featured the Strange Situation and Q-sort methods. The effects were larger for peer relations in middle childhood and adolescence than for peer relations in early childhood. ESs were also higher for studies that focused on children's close friendships rather than on relations with other peers. Gender and cultural differences in ESs were minimal. The results for the few studies on father-child attachment were inconclusive. PMID- 11206437 TI - Design and synthesis of new potent human cytomegalovirus (HCMV) inhibitors based on internally hydrogen-bonded 1,6-naphthyridines. AB - 1,6-Naphthyridine-2-carboxylic acid benzylamides are potent anti-HCMV compounds. Replacement of the amide moiety by other groups containing internal hydrogen bonds was undertaken to extend the SAR. Our results indicated that the urca derivatives showed very good activity. PMID- 11206438 TI - Broad spectrum antiprotozoal agents that inhibit histone deacetylase: structure activity relationships of apicidin. Part 1. AB - Apicidin, a natural product recently isolated at Merck, inhibits both mammalian and protozoan histone deacetylases (HDACs). The conversion of apicidin, a nanomolar inhibitor of HDACs, into a series of side-chain analogues that display picomolar enzyme affinity is described within this structure-activity study. PMID- 11206439 TI - Broad spectrum antiprotozoal agents that inhibit histone deacetylase: structure activity relationships of apicidin. Part 2. AB - Recently isolated at Merck, apicidin inhibits both mammalian and protozoan histone deacetylases (HDACs). The conversion of apicidin, a nonselective nanomolar inhibitor of HDACs, into a series of picomolar indole-modified and parasite-selective tryptophan-replacement analogues is described within this structure-activity study. PMID- 11206440 TI - Which aminoglycoside ring is most important for binding? A hydropathic analysis of gentamicin, paromomycin, and analogues. AB - The NMR structures of gentamicin and paromomycin in complex with the A-site of Escherichia coli 16S ribosomal RNA were modified with molecular modeling to 12 analogues. The intermolecular interactions between these molecules and RNA were examined using the HINT (Hydropathic INTeractions) computational model to obtain interaction scores that have been shown previously to be related to free energy. The calculations correlated well with experimental binding data, and the interaction scores were used to analyze the specific structural features of each aminoglycoside that contribute to the overall binding with the 16S rRNA. Our calculations indicate that, while ring I binds to the main binding pocket of the rRNA A-site, ring IV of paromomycin-based aminoglycosides contributes significantly to the overall binding. PMID- 11206441 TI - 8-Amido-Bearing pseudomycin B (PSB) analogue: novel antifungal agents. AB - During the course of a structure-activity relationship (SAR) study on novel depsinonapeptide pseudomycin B, we synthesized a total of 12 8-amidopseudomycin analogues via standard two-step sequence from either ZPSB 2 or AllocPSB 3. A number of these amides exhibited good in vitro antifungal activities. PMID- 11206442 TI - Bioisosteres of 9-carboxymethyl-4-oxo-imidazo[1,2-a]indeno-[1,2-e]pyrazin-2 carboxylic acid derivatives. Progress towards selective, potent in vivo AMPA antagonists with longer durations of action. AB - A novel series of 2- and 9-disubstituted heterocyclic-fused 4-oxo-indeno[1,2 e]pyrazin derivatives was synthesized. One of them, the 9-(1H-tetrazol-5 ylmethyl)-4-oxo-5,10-dihydroimidazo[1,2-a]indeno[1,2-e]pyrazin-2-yl phosphonic acid 4i exhibited a strong and a selective binding affinity for the AMPA receptor (IC50 = 13 nM) and demonstrated potent antagonist activity (IC50 = 6nM) at the ionotropic AMPA receptor. This compound also displayed good anticonvulsant properties against electrically-induced convulsions after ip and iv administration with ED50 values between 0.8 and 1 mg/kg. Furthermore, a strong increase in potency was observed when given iv 3 h before test (ED50 = 3.5 instead of 25.6 mg/kg for the corresponding 9-carboxymethyl-2-carboxylic acid analogue). These data confirmed that there is an advantage in replacing the classical carboxy substituents by their bioisosteres such as tetrazole or phosphonic acid groups. PMID- 11206443 TI - S-adenosylmethionine reverses ilimaquinone's vesiculation of the Golgi apparatus: a fluorescence study on the cellular interactions of ilimaquinone. AB - The marine sponge metabolite ilimaquinone has a wide range of biological activities, including vesiculation of the Golgi apparatus and interference with intracellular protein trafficking. Some of these activities may arise from ilimaquinone's influence on the activated methyl cycle. To visualize the morphological effects of ilimaquinone on the Golgi apparatus, NRK (normal rat kidney) cells were labeled with fluorescent wheat germ agglutinin and treated with ilimaquinone in the presence and absence of the methylating agent S adenosylmethionine (SAMe). While ilimaquinone alone fragments the Golgi apparatus, the organelle remains intact when SAMe is included in the incubation mixture. This observation supports ilimaquinone's interaction with methylation enzymes as the cause of Golgi vesiculation. The examination of a fluorescently labeled ilimaquinone analogue in NRK cells suggests that the cellular interactions of ilimaquinone are not localized to the Golgi apparatus. PMID- 11206444 TI - New anti-MRSA cephalosporins with a basic aminopyridine at the C-7 position. AB - Incorporation of a basic aminopyridine into the C-7 position of 3-(amine substituted arylthio)-3-norcephalosporins, as in 3, afforded high potency against MRSA and acceptable solubility for intravenous administration. PMID- 11206445 TI - Hydrolase and sialyltransferase activities of trypanosoma cruzi trans-sialidase towards NeuAc-alpha-2,3-gal-Gal-beta-O-PNP. AB - NeuAc-alpha-2,3-Gal-beta-O-PNP has been synthesised and its ability to act as a substrate for the hydrolase and transferase activities of Trypanosoma cruzi trans sialidase have been investigated. The turn-over of this compound shows marked differences from the behaviour of NeuAc-MU. In addition, distinct differences in the action of T. cruzi trans-sialidase and Clostridium perfringens neuraminidase on NeuAc-alpha-2,3-Gal-beta-O-PNP were apparent. PMID- 11206446 TI - Chemical synthesis of UDP-beta-L-arabinofuranose and its turnover to UDP-beta-L arabinopyranose by UDP-galactopyranose mutase. AB - Uridine-5'-diphospho-beta-L-arabinofuranose, a possible donor of L arabinofuranose residues in plants, was synthesized. This compound, in the presence of UDP-galactopyranose mutase, underwent interconversion with UDP-beta-L arabinopyranose that is a likely precursor of L-arabinofuranose in vivo. This result provided a working model for the biogenesis of arabinofuranose in plants. PMID- 11206447 TI - Design and synthesis of sialyl Lewis x mimics as E-selectin inhibitors. AB - The design and synthesis of novel beta-C-mannosides that inhibit the binding of sialyl Lewis x to E-selectin are described. Compounds that contained a phenyl substituent at the C-6 position were found to have increased potency. PMID- 11206448 TI - Synthesis and P2Y receptor activity of a series of uridine dinucleoside 5' polyphosphates. AB - A series of dinucleoside 5-polyphosphates UpnU (n = 2-7) was synthesized. Their relative potencies as agonists at the G-protein-coupled receptors P2Y1, P2Y2, P2Y4, and P2Y6 were determined by intracellular calcium measurements using fluorescent imaging techniques. The correlation of phosphate chain length to activities at these receptors is discussed. PMID- 11206449 TI - The synthesis of pseudomycin C' via a novel acid promoted side-chain deacylation of pseudomycin A. AB - The gamma hydroxyl present in the aliphatic side chain of the natural products pseudomycin A and C' provided a unique handle for the pH dependent side-chain deacylation. Low pH reaction conditions were used to cleave the side chain with minimal degradation of the peptide core. The pseudomycin nucleus intermediate obtained from the deacylation of pseudomycin A was pivotal in the synthesis of novel side-chain analogues. A practical synthesis of a minor fermentation factor pseudomycin C' and related analogues is reported. PMID- 11206450 TI - 2,2-Dimethyl-4,5-diaryl-3(2H)furanone derivatives as selective cyclo-oxygenase-2 inhibitors. AB - A series of 2,2-dimethyl-5-[4-(methylsulfonyl)phenyl]-4-phenyl-3(2H)furanones was prepared and evaluated for their ability to inhibit cyclo-oxygenase-2 (COX-2). PMID- 11206451 TI - Studies directed towards the refinement of the pancratistatin cytotoxic pharmacophore. AB - Two deoxy-analogues of the anticancer/antiviral agent pancratistatin containing functionality complementary to the minimum structural pharmacophore were synthesized and subjected to anticancer screening. One of the analogues exhibited selective inhibition of certain tumor cell lines but was significantly less potent than the natural products. The minimum structural pharmacophore has now been refined from eight to three possible structures. PMID- 11206452 TI - 3-Deoxy-3-substituted-D-myo-inositol imidazolyl ether lipid phosphates and carbonate as inhibitors of the phosphatidylinositol 3-kinase pathway and cancer cell growth. AB - 3-Modified D-myo-inositol imidazolyl ether lipid phosphates and a carbonate were synthesized and evaluated as inhibitors of P13-K and Akt. These data are presented along with IC50 values for the inhibition of the growth of three cancer cell lines. PMID- 11206453 TI - Atropisomeric quinazolin-4-one derivatives are potent noncompetitive alpha-amino 3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists. AB - Piriqualone (1) was found to be an antagonist of AMPA receptors. Structure activity optimization was conducted on each of the three rings in 1 to afford a series of potent and selective antagonists. The sterically crowded environment surrounding the N-3 aryl group provided sufficient thermal stability for atropisomers to be isolated. Separation of these atropisomers resulted in the identification of (+)-38 (CP-465,022), a compound that binds to the AMPA receptor with high affinity (IC50 = 36 nM) and displays potent anticonvulsant activity. PMID- 11206454 TI - 3,28-Di-O-(dimethylsuccinyl)-betulin isomers as anti-HIV agents. AB - Four isomers of 3,28-di-O-(dimethylsuccinyl)-betulin were prepared and evaluated for anti-HIV activity against HIV-1 replication in H9 lymphocyte cells. 3-O (3',3'-Dimethylsuccinyl)-28-O-(2", 2"-dimethvlsuccinyl)-betulin (11) was the most potent anti-HIV compound with an EC5, value of 0.00087 microM and a TI value of 42,400. PMID- 11206455 TI - Synthesis and antiparasitic activity of 2-(trifluoromethyl)-benzimidazole derivatives. AB - 2-(Trifluoromethyl)benzimidazole derivatives substituted at the 1-, 5-, and 6 positions have been synthesized and in vitro tested against the protozoa Giardia lamblia, Entamnoeha histolytica. and the helminth Trichinella spiralis. Results indicate that all the compounds tested are more active as antiprotozoal agents than Albendazole and Metronidazole. One compound (20) was as active as Albendazole against T. spiralis. These compounds were also tested for their effect on tubulin polymerization and none inhibited tubulin polymerization. PMID- 11206456 TI - High-pressure synthesis of enantiomerically pure C-6 substituted pyrazol. AB - The synthesis of enantiomerically pure C-6 substituted pyrazolo[3,4-d]pyrimidines has been performed by aromatic nucleophilic substitution of 4-amino-6-chloro-1 phenylpyrazolo[3,4-rd]pyrimidine under conditions of high pressure at ambient temperature. Conventional synthetic conditions (reflux at atmospheric pressure) were unsuccessful. The S enantiomer 11 displayed higher affinity and selectivity for the adenosine A1 receptor than the R enantiomer 12. PMID- 11206458 TI - Diastereoselective synthesis, activity and chiral stability of cyclic alkoxyketone inhibitors of cathepsin K. AB - The diastereoselective synthesis of a novel class of cathepsin K inhibitors together with their cathepsin K affinity and stability towards aqueous buffer is reported. PMID- 11206457 TI - Solid-phase synthesis of cyclic alkoxyketones, inhibitors of the cysteine protease cathepsin K. AB - Using solid-phase synthesis, a library of novel cyclic alkoxyketones has been constructed which show strong inhibitory activity against the cysteine protease, cathepsin K (EC 3.4.22.38). PMID- 11206459 TI - Inhibition of hepatitis C virus NS3 protease activity by product-based peptides is dependent on helicase domain. AB - Structure activity relationships (SARs) of product-based inhibitors of hepatitis C virus NS3 protease were evaluated using an in vitro assay system comprising the native bifunctional full-length NS3 (protease-helicase/NTPase). The results were compared to previously reported data derived from the corresponding NS3 protease domain assay. Shortening the length of the protease inhibitors from hexapeptides to tripeptides revealed that the decrease in potency was much less when determined in the assay system with the full-length NS3 protein. Disagreements in SARs at different positions (P5 P2) were also discovered. Taken together, the results suggest that the impact of the helicase domain upon protease inhibitor binding is substantial. PMID- 11206460 TI - Dimeric beta-turn peptidomimetics as ligands for the neurotrophin receptor TrkC. AB - Twelve dimeric peptidomimetics 1 were prepared via a divergent-convergent strategy. These peptidomimetics incorporated the same amino acids as i +1 and i + 2 residues in key beta-turns of the neurotrophin NT-3. Cytosensor microphysiometry was used to gauge the effects of the dimers 1 on cells that overexpress the NT-3 receptor, TrkC. Increases in extracellular acidification rates were observed for some monomers 3, but the active dimers gave greater effects. PMID- 11206461 TI - 3,3a-Dihydropyrano[4,3,2-de]quinazolin-2(1H)-ones are potent non-nucleoside reverse transcriptase inhibitors. AB - A series of unique 3,3a-dihydropyrano[4,3,2-de]quinazolin-2(1H)-ones and a 2a,5 dihydro-2H-thieno[4,3,2-de]quinazo-line-4(3H)-thione were found to be HIV-1 non nucleoside reverse transcriptase inhibitors. One of these compounds, as the racemate, possessed an IC90 = 4.6 nM against wild-type virus in a whole cell antiviral assay and had an IC90 = 76 and 897 nM against the clinically significant K103N and K103N/L100I mutant viruses, respectively. PMID- 11206462 TI - Synthesis and evaluation of caffeic acid amides as antioxidants. AB - A series of amides of caffeic acid has been synthesised and their antioxidant properties evaluated as lipid peroxidation inhibitors. Anilides of caffeic acid were found to be very efficient antioxidants with IC50's of 0.3 microM. PMID- 11206463 TI - Design, synthesis, and biological evaluation of HIV/FIV protease inhibitors incorporating a conformationally constrained macrocycle with a small P3' residue. AB - A series of norstatine-based HIV/FIV protease inhibitors incorporating a 15 membered macrocycle as a mimic of the tripeptide (Ala-Val-Phe), a motif with a small P3' residue elective against the FIV protease and the drug-resistant HIV proteases, has been synthesized. It was found that the macrocycle is important to the overall activity of the inhibitors. Certain inhibitors were developed expressing low nanomolar inhibitory activity against the HIV/FIV proteases and they are also effective against some drug-resistant as well as TL3-resistant HIV proteases. PMID- 11206464 TI - Synthesis and dopaminergic properties of the two enantiomers of 3-(3,4 dimethylphenyl)-1-propylpiperidine, a potent and selective dopamine D4 receptor ligand. AB - The synthesis of the two enantiomers of 3-(3,4-dimethylphenyl)-1-propylpiperidine 1, a potent and selective D4 dopaminergic ligand, was performed. The 3-(3,4 dimethylphenyl)- 1-propylpiperidine with the R configuration showed an affinity for the D4 receptors 6-fold higher than the corresponding enantiomer with the S configuration. Furthermore, the (R)-1 enantiomer proved to be highly selective for D4 receptors with respect to D2-D3 receptors, with a Ki ratio higher than 25,000, while the (S)-1 enantiomer was about 100-fold less selective than the (R) 1 one. PMID- 11206465 TI - Solid-phase optimisation of achiral amidinobenzyl indoles as potent and selective factor Xa inhibitors. AB - Starting from the achiral and potent factor Xa inhibitor 1, a new and flexible solid-phase optimisation strategy is described to reduce its cationic character. By replacing one positively charged side chain by a lipophilic substituent, a novel series of highly potent and selective achiral factor Xa inhibitors was discovered. The identified lipophilic replacements in the S4 pocket might be valuable for other approaches towards fXa inhibitors. PMID- 11206466 TI - Structure--activity relationships of side-chain modified didemnins. AB - The synthesis and antitumor activity of a novel didemnin B analogue containing a psi[CH2NH] amide bond surrogate between N-Me-D-Leu7 and Pro8 are reported. The analogue shows activity (GI50 = 4 nM) comparable to that of didemnin B (GI50 = 13 nM) in the NCI-60 tumor cell screen. This result, along with new data from previously reported synthetic didemnin analogues, is discussed within the context of the side-chain SAR for didemnins. PMID- 11206467 TI - The discovery of anthranilic acid-based MMP inhibitors. Part 1: SAR of the 3 position. AB - A novel series of anthranilic acid-based inhibitors of MMP-1, MMP-9, and MMP-13 was prepared and evaluated both in vitro and in vivo. The most potent compound, 6e, has in vivo activity in a rat sponge-wrapped cartilage model. PMID- 11206468 TI - Heteroaryl and cycloalkyl sulfonamide hydroxamic acid inhibitors of matrix metalloproteinases. AB - Heteroaryl and cycloalkyl sulfonamide-hydroxamic acid MMP inhibitors were investigated. Of these, the pyridyl analogue 2 is the most potent and selective inhibitor of MMP-9 and MMP-13 in vitro. PMID- 11206469 TI - Intracellular inhibition of human neutrophil elastase by orally active pyrrolidine-trans-lactams. AB - Described are the acylation binding of trans-lactam 1 to porcine pancreatic elastase, the selection of the SO2Me activating group for the lactam N which also confers metabolic stability in hamster liver microsomes, the introduction of aqueous solubility through the piperidine salt 9, the in vivo oral activity of 9 and its bioavailability, and the introduction of 9 as an intracellular neutrophil elastase inhibitor. PMID- 11206470 TI - Synthesis, absolute configuration and antimuscarinic activity of the enantiomers of [1-(2,2-diphenyl-[1,3]dioxolan-4-yl)-ethyl]-dimethyl-amine. AB - Methylation of the carbon atom C of compound 1, a potent and not selective muscarinic antagonist, was carried out. The resulting diastereomers were separated and the corresponding racemate further resolved to give four enantiomers, which were tested both as hydrogen oxalate and methiodide salts. The pharmacological results obtained at M1, M2 and M3 muscarinic receptor subtypes, show that methylation at C1, depending on the stereochemistry, increases antagonist potency, having thus the same effect of nitrogen quaternization. These results may well lead to the development of new potent antimuscarinic drugs lacking a cationic head. PMID- 11206471 TI - Polyamines with N-(3-phenylpropyl) substituents are effective competitive inhibitors of trypanothione reductase and trypanocidal agents. AB - Several N-(3-phenylpropyl)-substituted spermidine and spermine derivatives were prepared and found to be potent competitive inhibitors of Trypanosoma cruzi trypanothione reductase (seven compounds with Ki values < 5 microM are described). The most effective inhibitor studied was compound 12 with a Ki value of 0.151 microM. Six of the compounds described are also effective trypanocides with IC50 values < 1 microM. PMID- 11206472 TI - 3-p-Toluoyl-2-[4'-(3-diethylaminopropoxy)-phenyl]-benzofuran and 2-[4'-(3 diethylaminopropoxy)-phenyl]-benzofuran do not act as surfactants or micelles when inhibiting the aggregation of beta-amyloid peptide. AB - The cmc and IC50 values of the beta-amyloid (Abeta) aggregation inhibitors, 3-p toluoyl-2-[4'-(3-diethylaminopropoxy)-phenyl]-benzofuran 1, and 2-[4'-(3 diethylaminopropoxy)-phenyl]-benzofuran 2 have been determined. After comparison of the cmc data and biological data (IC50 values), we conclude that these active benzofurans do not act as surfactants or micelles at the concentration required to inhibit beta-amyloid-peptide aggregation. PMID- 11206473 TI - Antagonists of the human CCR5 receptor as anti-HIV-1 agents. part 1: discovery and initial structure-activity relationships for 1 -amino-2-phenyl-4-(piperidin-1 yl)butanes. AB - Screening of the Merck sample collection for compounds with CCR5 receptor binding afforded (2S)-2-(3,4-dichlorophenyl)-1-[N-(methyl)-N-(phenylsulfonyl)amino]-4 [spiro(2,3-dihydrobenzthiophene-3,4'-piperidin-1'-yl)]butane S-oxide (4) as a potent lead structure having an IC50 binding affinity of 35 nM. Herein, we describe the discovery of this lead structure and our initial structure activity relationship studies directed toward the requirement for and optimization of the 1-amino fragment. PMID- 11206474 TI - Antagonists of the human CCR5 receptor as anti-HIV-1 agents. Part 2: structure activity relationships for substituted 2-Aryl-1-[N-(methyl)-N (phenylsulfonyl)amino]-4-(piperidin-1-yl)butanes. AB - (2S)-2-(3,4-Dichlorophenyl)-1-[N-(methyl)-N-(phenylsulfonyl)amino]-4-[spiro(2,3 dihydrobenzthiophene-3,4'-piperidin-1'-yl)]butane S-oxide (3) has been identified as a potent CCR5 antagonist lead structure having an IC50 = 35 nM. Herein, we describe the structure-activity relationship studies directed toward the requirement for and optimization of the C-2 phenyl fragment. The phenyl was found to be important for CCR5 antagonism and substitution was limited to small moieties at the 3-position (13 and 16: X= H, 3-F, 3-Cl, 3-Me). PMID- 11206475 TI - Liquid-phase parallel synthesis of ureas. AB - An efficient and general liquid-phase method has been developed for the synthesis of a piperazine containing urea library. Reactions of the polymer bound carbamoyl chloride with primary or secondary amines afford ureas at ambient temperature. Desired compounds are liberated from the polymer support under mild conditions in high yields and high purity by simple precipitation and washings. PMID- 11206476 TI - Synthesis and structure--activity analysis of novel dihydropyridine derivatives to overcome multidrug resistance. AB - The structure activity relationships were studied on newly synthesized 1,4 dihydropyridine derivatives possessing a 1-pentyl group at the 4-position, and 3 pyridylpropylester was found to be one of the effective fragments for overcoming P-glycoprotein mediated multidrug-resistance (MDR) in cultured human cancer cells, in vitro. 3-Pyridylpropylester was also found to be one of the effective fragments for increasing the life span of P-glycoprotein overexpressing MDR P388 leukemia-bearing mice, in vivo. All compounds had weak calcium antagonistic activities, but there appeared no relationship between MDR reversing effect and calcium antagonistic activity. PMID- 11206477 TI - Cocaine catalytic antibodies: the primary importance of linker effects. AB - Current treatments for cocaine addiction are not effective. The development of a catalytic monoclonal antibody (mAb) provides a strategy for not only binding, but also degrading cocaine, which offers a broad-based therapy. Hapten design is the central element for programming antibody catalysis. The characteristics of the linker used in classic transition-state analogue phosphonate haptens were shown to be important for obtaining mAbs that hydrolyze the benzoate ester of cocaine. PMID- 11206479 TI - A disubstituted NAD+ analogue is a nanomolar inhibitor of trypanosomal glyceraldehyde-3-phosphate dehydrogenase. AB - N6-Naphthalenemethyl-2'-methoxybenzamido-beta-NAD+, a derivative of a low micromolar first-generation inhibitor of trypanosomal glyceraldehyde phosphate dehydrogenase (GAPDH), was synthesized, taking advantage of methodology for the selective phosphitylation of nucleosides. The compound was found to be a poor alternate cosubstrate for GAPDH, but an extremely potent inhibitor. Although intended for use in crystallization trials, the analogue presents possibilities for further drug design. PMID- 11206478 TI - Arylalkylidene rhodanine with bulky and hydrophobic functional group as selective HCV NS3 protease inhibitor. AB - Arylalkylidene rhodanines 2(a-d) inhibit HCV NS3 protease at moderate concentrations. They are better inhibitors of other serine proteases such as chymotrypsin and plasmin. However, the selectivity of arylmethyliden e rhodanines (8a, 9a) with bulkier and more hydrophobic functional groups increases by 13- and 25-fold towards HCV NS3 protease respectively. PMID- 11206481 TI - Human HOX gene mutations. AB - HOX genes play a fundamental role in the development of the vertebrate central nervous system, axial skeleton, limbs, gut, urogenital tract and external genitalia, but it is only in the last 4 years that mutations in two of the 39 human HOX genes have been shown to cause congenital malformations; HOXD13, which is mutated in synpolydactyly, and HOXA13, which is mutated in Hand-Foot-Genital syndrome. Here we review the mutations already identified in these two genes, consider how these mutations may act, and discuss the possibility that further mutations remain to be discovered both in developmental disorders and in cancer. PMID- 11206505 TI - Lessons from Huntingdon. PMID- 11206480 TI - Synthesis of 7,8-disubstituted benzolactam-V8 and its binding to protein kinase C. AB - 7-Methoxy-8-decynyl-benzolactam-V8 4 is synthesized using a catalytic asymmetric alkylation reaction as a key step. This compound shows potent activity to three PKC isozymes tested (Ki =45.6, 91.1, and 121.3 nM to PKCalpha, delta, and epsilon, respectively), indicating that introduction of a suitable substituent at the 7-position of 8-decynyl-benzolactam-V8 only slightly reduces the PKC binding affinity. PMID- 11206506 TI - Italians drop beef as first cow tests positive. PMID- 11206507 TI - Agencies face uphill battle to keep United States free of BSE. PMID- 11206509 TI - Students fuzzy about the future. PMID- 11206508 TI - Public have right to see data from all gene trials, says FDA. PMID- 11206511 TI - Max Planck Society broke pledge to ask Jews back after war. PMID- 11206510 TI - Animal-rights protests raise calls for UK government move. PMID- 11206513 TI - Canadian minister keeps researchers guessing. PMID- 11206514 TI - Assessment ups the ante on climate change. PMID- 11206512 TI - Health and energy chiefs sail through Senate. PMID- 11206515 TI - Demand for physicists on the rise. PMID- 11206517 TI - Nuclear physics. Bringing supernovae down to Earth. PMID- 11206516 TI - Stem-cell research to start in Britain. PMID- 11206518 TI - Santiago Ramon y Cajal. The brain in Spain. PMID- 11206519 TI - European researchers encourage improvement in lab animal welfare. PMID- 11206520 TI - Users must help to keep public databases correct. PMID- 11206521 TI - The long-term answer: fight fire with research. PMID- 11206522 TI - The suspense of strangeness. PMID- 11206524 TI - Quantum optics. Stopping light in its tracks. PMID- 11206523 TI - Natural progression. PMID- 11206525 TI - Extrasolar planets. Giant giants or dwarf dwarfs? PMID- 11206526 TI - Gastrogenomics. PMID- 11206527 TI - The age of river carbon. PMID- 11206528 TI - Walking on other planets. PMID- 11206529 TI - Plant biology. Floral quartets. PMID- 11206530 TI - Watching an atom tunnel. PMID- 11206531 TI - A new code for axons. PMID- 11206532 TI - Sperm and mammalian polarity. PMID- 11206533 TI - Watching fights raises fish hormone levels. PMID- 11206534 TI - Light-emitting diodes as chemical sensors. PMID- 11206535 TI - Screening slaughtered cattle for BSE. PMID- 11206536 TI - Gene capture in archaeal chromosomes. PMID- 11206537 TI - The architecture of active zone material at the frog's neuromuscular junction. AB - Active zone material at the nervous system's synapses is situated next to synaptic vesicles that are docked at the presynaptic plasma membrane, and calcium channels that are anchored in the membrane. Here we use electron microscope tomography to show the arrangement and associations of structural components of this compact organelle at a model synapse, the frog's neuromuscular junction. Our findings indicate that the active zone material helps to dock the vesicles and anchor the channels, and that its architecture provides both a particular spatial relationship and a structural linkage between them. The structural linkage may include proteins that mediate the calcium-triggered exocytosis of neurotransmitter by the synaptic vesicles during synaptic transmission. PMID- 11206538 TI - Dynamos in asymptotic-giant-branch stars as the origin of magnetic fields shaping planetary nebulae. AB - Planetary nebulae are thought to be formed when a slow wind from the progenitor giant star is overtaken by a subsequent fast wind generated as the star enters its white dwarf stage. A shock forms near the boundary between the winds, creating the relatively dense shell characteristic of a planetary nebula. A spherically symmetric wind will produce a spherically symmetric shell, yet over half of known planetary nebulae are not spherical; rather, they are elliptical or bipolar in shape. A magnetic field could launch and collimate a bipolar outflow, but the origin of such a field has hitherto been unclear, and some previous work has even suggested that a field could not be generated. Here we show that an asymptotic-giant-branch (AGB) star can indeed generate a strong magnetic field, having as its origin a dynamo at the interface between the rapidly rotating core and the more slowly rotating envelope of the star. The fields are strong enough to shape the bipolar outflows that produce the observed bipolar planetary nebulae. Magnetic braking of the stellar core during this process may also explain the puzzlingly slow rotation of most white dwarf stars. PMID- 11206539 TI - Geochemical evidence for magmatic water within Mars from pyroxenes in the Shergotty meteorite. AB - Observations of martian surface morphology have been used to argue that an ancient ocean once existed on Mars. It has been thought that significant quantities of such water could have been supplied to the martian surface through volcanic outgassing, but this suggestion is contradicted by the low magmatic water content that is generally inferred from chemical analyses of igneous martian meteorites. Here, however, we report the distributions of trace elements within pyroxenes of the Shergotty meteorite--a basalt body ejected 175 million years ago from Mars--as well as hydrous and anhydrous crystallization experiments that, together, imply that water contents of pre-eruptive magma on Mars could have been up to 1.8%. We found that in the Shergotty meteorite, the inner cores of pyroxene minerals (which formed at depth in the martian crust) are enriched in soluble trace elements when compared to the outer rims (which crystallized on or near to the martian surface). This implies that water was present in pyroxenes at depth but was largely lost as pyroxenes were carried to the surface during magma ascent. We conclude that ascending magmas possibly delivered significant quantities of water to the martian surface in recent times, reconciling geologic and petrologic constraints on the outgassing history of Mars. PMID- 11206540 TI - Observation of coherent optical information storage in an atomic medium using halted light pulses. AB - Electromagnetically induced transparency is a quantum interference effect that permits the propagation of light through an otherwise opaque atomic medium; a 'coupling' laser is used to create the interference necessary to allow the transmission of resonant pulses from a 'probe' laser. This technique has been used to slow and spatially compress light pulses by seven orders of magnitude, resulting in their complete localization and containment within an atomic cloud. Here we use electromagnetically induced transparency to bring laser pulses to a complete stop in a magnetically trapped, cold cloud of sodium atoms. Within the spatially localized pulse region, the atoms are in a superposition state determined by the amplitudes and phases of the coupling and probe laser fields. Upon sudden turn-off of the coupling laser, the compressed probe pulse is effectively stopped; coherent information initially contained in the laser fields is 'frozen' in the atomic medium for up to 1 ms. The coupling laser is turned back on at a later time and the probe pulse is regenerated: the stored coherence is read out and transferred back into the radiation field. We present a theoretical model that reveals that the system is self-adjusting to minimize dissipative loss during the 'read' and 'write' operations. We anticipate applications of this phenomenon for quantum information processing. PMID- 11206541 TI - Formation cross-sections of singlet and triplet excitons in pi-conjugated polymers. AB - Electroluminescence in organic light-emitting diodes arises from a charge transfer reaction between the injected positive and negative charges by which they combine to form singlet excitons that subsequently decay radiatively. The quantum yield of this process (the number of photons generated per electron or hole injected) is often thought to have a statistical upper limit of 25 per cent. This is based on the assumption that the formation cross-section of singlet excitons, sigmaS, is approximately the same as that of any one of the three equivalent non-radiative triplet exciton states, sigmaT; that is, sigmaS/sigmaT approximately 1. However, recent experimental and theoretical work suggests that sigmaS/sigmaT may be greater than 1. Here we report direct measurements of sigmaS/sigmaT for a large number of pi-conjugated polymers and oligomers. We have found that there exists a strong systematic, but not monotonic, dependence of sigmaS/sigmaT on the optical gap of the organic materials. We present a detailed physical picture of the charge-transfer reaction for correlated pi-electrons, and quantify this process using exact valence bond calculations. The calculated sigmaS/sigmaT reproduces the experimentally observed trend. The calculations also show that the strong dependence of sigmaS/sigmaT on the optical gap is a signature of the discrete excitonic energy spectrum, in which higher energy excitonic levels participate in the charge recombination process. PMID- 11206543 TI - Geochemical evidence for the melting of subducting oceanic lithosphere at plate edges. AB - Most island-arc magmatism appears to result from the lowering of the melting point of peridotite within the wedge of mantle above subducting slabs owing to the introduction of fluids from the dehydration of subducting oceanic crust. Volcanic rocks interpreted to contain a component of melt (not just a fluid) from the subducting slab itself are uncommon, but possible examples have been recognized in the Aleutian islands, Baja California, Patagonia and elsewhere. The geochemically distinctive rocks from these areas, termed 'adakites, are often associated with subducting plates that are young and warm, and therefore thought to be more prone to melting. But the subducting lithosphere in some adakite locations (such as the Aleutian islands) appears to be too old and hence too cold to melt. This implies either that our interpretation of adakite geochemistry is incorrect, or that our understanding of the tectonic context of adakites is incomplete. Here we present geochemical data from the Kamchatka peninsula and the Aleutian islands that reaffirms the slab-melt interpretation of adakites, but in the tectonic context of the exposure to mantle flow around the edge of a torn subducting plate. We conclude that adakites are likely to form whenever the edge of a subducting plate is warmed or ablated by mantle flow. The use of adakites as tracers for such plate geometry may improve our understanding of magma genesis and thermal structure in a variety of subduction-zone environments. PMID- 11206542 TI - Riverine export of aged terrestrial organic matter to the North Atlantic Ocean. AB - Global riverine discharge of organic matter represents a substantial source of terrestrial dissolved and particulate organic carbon to the oceans. This input from rivers is, by itself, more than large enough to account for the apparent steady-state replacement times of 4,00-6,000 yr for oceanic dissolved organic carbon. But paradoxically, terrestrial organic matter, derived from land plants, is not detected in seawater and sediments in quantities that correspond to its inputs. Here we present natural 14C and 13C data from four rivers that discharge to the western North Atlantic Ocean and find that these rivers are sources of old (14C-depleted) and young (14C-enriched) terrestrial dissolved organic carbon, and of predominantly old terrestrial particulate organic carbon. These findings contrast with limited earlier data that suggested terrestrial organic matter transported by rivers might be generally enriched in 14C from nuclear testing, and hence newly produced. We also find that much of the young dissolved organic carbon can be selectively degraded over the residence times of river and coastal waters, leaving an even older and more refractory component for oceanic export. Thus, pre-ageing and degradation may alter significantly the structure, distributions and quantities of terrestrial organic matter before its delivery to the oceans. PMID- 11206544 TI - A bizarre predatory dinosaur from the Late Cretaceous of Madagascar. AB - Here we report the discovery of a small-bodied (approximately 1.8 m) predatory dinosaur from the Late Cretaceous (Maastrichtian) of Madagascar. Masiakasaurus knopfleri, gen. et sp. nov., represented by several skull elements and much of the postcranial skeleton, is unique in being the only known theropod with a highly procumbent and distinctly heterodont lower dentition. Such a derived dental morphology is otherwise unknown among dinosaurs. Numerous skeletal characteristics indicate that Masiakasaurus is a member of Abelisauroidea, an enigmatic clade of Gondwanan theropods. Previously, small-bodied abelisauroids were known only from Argentina. The occurrence of Masiakasaurus on Madagascar suggests that small-bodied abelisauroids, like their larger-bodied counterparts, were more cosmopolitan, radiating throughout much of Gondwana and paralleling the diversification of small coelurosaur theropods in Laurasia. PMID- 11206545 TI - Archaeal dominance in the mesopelagic zone of the Pacific Ocean. AB - The ocean's interior is Earth's largest biome. Recently, cultivation-independent ribosomal RNA gene surveys have indicated a potential importance for archaea in the subsurface ocean. But quantitative data on the abundance of specific microbial groups in the deep sea are lacking. Here we report a year-long study of the abundance of two specific archaeal groups (pelagic euryarchaeota and pelagic crenarchaeota) in one of the ocean's largest habitats. Monthly sampling was conducted throughout the water column (surface to 4,750 m) at the Hawai'i Ocean Time-series station. Below the euphotic zone (> 150 m), pelagic crenarchaeota comprised a large fraction of total marine picoplankton, equivalent in cell numbers to bacteria at depths greater than 1,000 m. The fraction of crenarchaeota increased with depth, reaching 39% of total DNA-containing picoplankton detected. The average sum of archaea plus bacteria detected by rRNA-targeted fluorescent probes ranged from 63 to 90% of total cell numbers at all depths throughout our survey. The high proportion of cells containing significant amounts of rRNA suggests that most pelagic deep-sea microorganisms are metabolically active. Furthermore, our results suggest that the global oceans harbour approximately 1.3 x 10(28) archaeal cells, and 3.1 x 10(28) bacterial cells. Our data suggest that pelagic crenarchaeota represent one of the ocean's single most abundant cell types. PMID- 11206546 TI - Testing Hamilton's rule with competition between relatives. AB - Hamilton's theory of kin selection suggests that individuals should show less aggression, and more altruism, towards closer kin. Recent theoretical work has, however, suggested that competition between relatives can counteract kin selection for altruism. Unfortunately, factors that tend to increase the average relatedness of interacting individuals--such as limited dispersal--also tend to increase the amount of competition between relatives. Therefore, in most natural systems, the conflicting influences of increased competition and increased relatedness are confounded, limiting attempts to test theory. Fig wasp taxa exhibit varying levels of aggression among non-dispersing males that show a range of average relatedness levels. Thus, across species, the effects of relatedness and competition between relatives can be separated. Here we report that--contrary to Hamilton's original prediction but in agreement with recent theory--the level of fighting between males shows no correlation with the estimated relatedness of interacting males, but is negatively correlated with future mating opportunities. PMID- 11206547 TI - Reduced antinociception and plasma extravasation in mice lacking a neuropeptide Y receptor. AB - Neuropeptide Y (NPY) is believed to exert antinociceptive actions by inhibiting the release of substance P and other 'pain neurotransmitters' in the spinal cord dorsal horn. However, the physiological significance and potential therapeutic value of NPY remain obscure. It is also unclear which receptor subtype(s) are involved. To identify a possible physiological role for the NPY Y1 receptor in pain transmission, we generated NPY Y1 receptor null mutant (Y1-/-) mice by homologous recombination techniques. Here we show that Y1-/- mice develop hyperalgesia to acute thermal, cutaneous and visceral chemical pain, and exhibit mechanical hypersensitivity. Neuropathic pain is increased, and the mice show a complete absence of the pharmacological analgesic effects of NPY. In the periphery, Y1 receptor activation is sufficient and required for substance P release and the subsequent development of neurogenic inflammation and plasma leakage. We conclude that the Y1 receptor is required for central physiological and pharmacological NPY-induced analgesia and that its activation is both sufficient and required for the release of substance P and initiation of neurogenic inflammation. PMID- 11206548 TI - Role for sperm in spatial patterning of the early mouse embryo. AB - Despite an apparent lack of determinants that specify cell fate, spatial patterning of the mouse embryo is evident early in development. The axis of the post-implantation egg cylinder can be traced back to organization of the pre implantation blastocyst. This in turn reflects the organization of the cleavage stage embryo and the animal-vegetal axis of the zygote. These findings suggest that the cleavage pattern of normal development may be involved in specifying the future embryonic axis; however, how and when this pattern becomes established is unclear. In many animal eggs, the sperm entry position provides a cue for embryonic patterning, but until now no such role has been found in mammals. Here we show that the sperm entry position predicts the plane of initial cleavage of the mouse egg and can define embryonic and abembryonic halves of the future blastocyst. In addition, the cell inheriting the sperm entry position acquires a division advantage and tends to cleave ahead of its sister. As cell identity reflects the timing of the early cleavages, these events together shape the blastocyst whose organization will become translated into axial patterning after implantation. We present a model for axial development that accommodates these findings with the regulative nature of mouse embryos. PMID- 11206549 TI - Adherens junctions inhibit asymmetric division in the Drosophila epithelium. AB - Asymmetric division is a fundamental mechanism for generating cellular diversity. In the central nervous system of Drosophila, neural progenitor cells called neuroblasts undergo asymmetric division along the apical-basal cellular axis. Neuroblasts originate from neuroepithelial cells, which are polarized along the apical-basal axis and divide symmetrically along the planar axis. The asymmetry of neuroblasts might arise from neuroblast-specific expression of the proteins required for asymmetric division. Alternatively, both neuroblasts and neuroepithelial cells could be capable of dividing asymmetrically, but in neuroepithelial cells other polarity cues might prevent asymmetric division. Here we show that by disrupting adherens junctions we can convert the symmetric epithelial division into asymmetric division. We further confirm that the adenomatous polyposis coli (APC) tumour suppressor protein is recruited to adherens junctions, and demonstrate that both APC and microtubule-associated EB1 homologues are required for the symmetric epithelial division along the planar axis. Our results indicate that neuroepithelial cells have all the necessary components to execute asymmetric division, but that this pathway is normally overridden by the planar polarity cue provided by adherens junctions. PMID- 11206550 TI - Complexes of MADS-box proteins are sufficient to convert leaves into floral organs. AB - Genetic studies, using floral homeotic mutants, have led to the ABC model of flower development. This model proposes that the combinatorial action of three sets of genes, the A, B and C function genes, specify the four floral organs (sepals, petals, stamens and carpels) in the concentric floral whorls. However, attempts to convert vegetative organs into floral organs by altering the expression of ABC genes have been unsuccessful. Here we show that the class B proteins of Arabidopsis, PISTILLATA (PI) and APETALA3 (AP3), interact with APETALA1 (AP1, a class A protein) and SEPALLATA3 (SEP3, previously AGL9), and with AGAMOUS (AG, a class C protein) through SEP3. We also show that vegetative leaves of triply transgenic plants, 35S::PI;35S::AP3;35S::AP1 or 35S::PI;35S::AP3;35S::SEP3, are transformed into petaloid organs and that those of 35S::PI;35S::AP3;35S::SEP3;35S::AG are transformed into staminoid organs. Our findings indicate that the formation of ternary and quaternary complexes of ABC proteins may be the molecular basis of the ABC model, and that the flower specific expression of SEP3 restricts the action of the ABC genes to the flower. PMID- 11206551 TI - Genome sequence of enterohaemorrhagic Escherichia coli O157:H7. AB - The bacterium Escherichia coli O157:H7 is a worldwide threat to public health and has been implicated in many outbreaks of haemorrhagic colitis, some of which included fatalities caused by haemolytic uraemic syndrome. Close to 75,000 cases of O157:H7 infection are now estimated to occur annually in the United States. The severity of disease, the lack of effective treatment and the potential for large-scale outbreaks from contaminated food supplies have propelled intensive research on the pathogenesis and detection of E. coli O157:H7 (ref. 4). Here we have sequenced the genome of E. coli O157:H7 to identify candidate genes responsible for pathogenesis, to develop better methods of strain detection and to advance our understanding of the evolution of E. coli, through comparison with the genome of the non-pathogenic laboratory strain E. coli K-12 (ref. 5). We find that lateral gene transfer is far more extensive than previously anticipated. In fact, 1,387 new genes encoded in strain-specific clusters of diverse sizes were found in O157:H7. These include candidate virulence factors, alternative metabolic capacities, several prophages and other new functions--all of which could be targets for surveillance. PMID- 11206552 TI - Genomic binding sites of the yeast cell-cycle transcription factors SBF and MBF. AB - Proteins interact with genomic DNA to bring the genome to life; and these interactions also define many functional features of the genome. SBF and MBF are sequence-specific transcription factors that activate gene expression during the G1/S transition of the cell cycle in yeast. SBF is a heterodimer of Swi4 and Swi6, and MBF is a heterodimer of Mbpl and Swi6 (refs 1, 3). The related Swi4 and Mbp1 proteins are the DNA-binding components of the respective factors, and Swi6 mayhave a regulatory function. A small number of SBF and MBF target genes have been identified. Here we define the genomic binding sites of the SBF and MBF transcription factors in vivo, by using DNA microarrays. In addition to the previously characterized targets, we have identified about 200 new putative targets. Our results support the hypothesis that SBF activated genes are predominantly involved in budding, and in membrane and cell-wall biosynthesis, whereas DNA replication and repair are the dominant functions among MBF activated genes. The functional specialization of these factors may provide a mechanism for independent regulation of distinct molecular processes that normally occur in synchrony during the mitotic cell cycle. PMID- 11206553 TI - Arrangement of RNA and proteins in the spliceosomal U1 small nuclear ribonucleoprotein particle. AB - In eukaryotic cells, freshly synthesized messenger RNA (pre-mRNA) contains stretches of non-coding RNA that must be excised before the RNA can be translated into protein. Their removal is catalysed by the spliceosome, a large complex formed when a number of small nuclear ribonucleoprotein particles (snRNPs) bind sequentially to the pre-mRNA. The first snRNP to bind is called U1; other snRNPs (U2, U4/U6 and U5) follow. Here we describe the three-dimensional structure of human U1 snRNP, determined by single-particle electron cryomicroscopy at 10 A resolution. The reconstruction reveals a doughnut-shaped central element that accommodates the seven Sm proteins common to all snRNPs, supporting a proposed model of circular Sm protein arrangement. By taking earlier biochemical results into account, we were able to assign the remaining density of the map to the other known components of U1 snRNP, deriving a structural model that describes the three-dimensional arrangement of proteins and RNA in U1 snRNP. PMID- 11206554 TI - Laser Raman and IR spectra and force fields for 2,4-dichlorobenzonitrile. AB - Raman spectrum of 2,4-dichlorobenzonitrile (2,4-DCBN) in powder form has been recorded in the region 50-4000 cm(-1) on a Jasco K-500 Raman spectrophotometer using the 488.0 nm radiation from an argon laser. FTIR spectra in the region 200 4000 cm(-1) have been recorded in KBr pellet and nujol mull on a Nicolet DX spectrometer. Using the observed Raman and IR frequencies, normal co-ordinate analysis has been carried out to support the vibrational analysis and to determine the planar and non-planar force fields. PMID- 11206555 TI - Study on fluorescent property of degrading products of piperacillin and its analytical application. AB - The fluorimetric property of the degrading products of piperacillin has been studied in detail. The studies on degrading pH, degrading time, detection alkalinity and other corresponding analytical parameters of acid degradation have been made. Then fluorometry of piperacillin was established by producing its stable fluorescent products. The detection limit for acid degradation analytical method is 2.34 ng/ml, the linear range is 7.80-4.0 x 10(2) ppb. The analytical sensitivity, precision and stability of degrading products of acid degradation are satisfactory, which has been used for the determination of the trace piperacillin in human serum and urine with satisfactory results. PMID- 11206556 TI - Charge-transfer complex formation between o-chloranil and a series of polynuclear aromatic hydrocarbons. AB - The equilibrium constants, enthalpies and entropies of formation of molecular electron donor-acceptor (EDA) complexes of o-chloranil with a series of aromatic hydrocarbons have been determined spectrophotometrically. Spectroscopic and thermodynamic aspects of these complexes have been analysed. PMID- 11206557 TI - The effect of pressure and temperature on the vibrational spectra of different hydrogen bonded systems. AB - The effect of pressure and temperature on the vibrational spectra of hydrogen bonded systems has been studied on amides, thioamides, carboxylic acids and urea. The compounds under investigation are indicative for the kind of hydrogen bonding changing from pure intermolecular to intramolecular and dimeric forms. The discussion of the temperature dependence on the fundamentals involved in the hydrogen bonding is straightforward but the pressure data are much more complicated and only if the changes in the crystalline state at different pressures are known, we will have a better understanding of the dependence of some fundamentals in the hydrogen bonded systems. A clear example of this approach is given for urea. PMID- 11206558 TI - Vibrational spectroscopic study of DL-methionine dihydrogen phosphate. AB - The two methionine cations in the asymmetric part of the unit cell of bis(DL methionine dihydrogen phosphate) have different conformations. This, together with the different environments seen by the two -CH2- groups in each skeleton cause several of the group wavenumbers to occur as doublets or as broad bands. The anion contains two dissimilar P-O bonds, which distorts the phosphate tetrahedron. Due to this, the stretching wavenumbers appear as doublets. There is extensive hydrogen bonding in the system in all three crystallographic directions and this is responsible for the changes in the position and intensity of several bands. Fermi resonance has also been observed. PMID- 11206559 TI - The infrared intensities and polar tensors of the fluorochloromethanes. AB - The polar tensors of CF3Cl, CF2Cl2 and CFCl3 have been calculated using recent measurements of their gas phase infrared fundamental intensities. The polar tensors obtained for CF2Cl2 and CFCl3 are in very good agreement with those obtained previously since the more recent experimental intensity results are in good agreement with those reported earlier. For CF2Cl2 rhoC = +1.626, rhoF = 0.577 and rhoCl = -0.26e whereas rhoC = +1.369, 0.478 and rhoCl = 0.297e for CFCl3. However, two sets of significantly different mean dipole moment derivatives are obtained from the experimentally measured intensities of CF3Cl reported by two different laboratories. On the other hand, the differences in the mean derivatives of these two sets are not large enough so that results from electronegativity models, potential models for core ionization energies and quantum chemical calculations at the Moller-Plesset 2 and B3LYP density functional levels are sufficient to indicate which set is the correct one. As such average values of rhoC = +1.907+/-0.178e, rhoF = -0.590+/-0.056e and rhoCl = -0.139+/-0.013e obtained from both sets of polar tensor elements are recommended for the CF33Cl mean dipole moment derivatives. PMID- 11206560 TI - Molecular structure and vibrational spectra of phenolphthalein and its dianion. AB - Infrared (IR) and Raman spectra of phenolphthalein (PP) and its dianion form (sodium and potassium salts) were studied both in the solid state and in aqueous solution. Band assignments were carried out on the basis of the isotope shifts of the ring deuterated and 13C-substituted derivatives. Spectral analyses reveal that the PP dianion exists as mixtures of the benzenoid form (colorless) and the quinonoid form (colored) in the solid state and in aqueous solution, while the neutral PP solely takes the gamma-lactone form. This work provides the first vibrational spectroscopic evidence for the coexistence of the two species in the PP dianions. PMID- 11206561 TI - Thermal and optical properties of Tm3+ doped tellurite glasses. AB - Ultraviolet, visible (UV/VIS) and differential thermal analysis (DTA) measurements were carried out in order to investigate the optical and thermal properties of various 0.5 mol.% Tm2O3 containing (1 - x)TeO2 + xLiCl glasses in molar ratio. The samples were prepared by fusing the mixture of their respective reagent grade powders in a platinum cricuble at 750 degrees C for 30 min. DTA curves taken in the 23-600 degrees C temperature range with a heating rate of 10 degrees C/min reveal a change in the value of the glass transition temperature, Tg, while melting was not observed for the glasses containing LiCl content less than 50 mol.%. These glasses were found to be moisture-resistant. However, the glasses with LiCl content higher than 50 mol.%, in which a melting peak was observed at Tc = 401 degrees C, were moisture-sensitive. Absorption measurements in the UV/VIS region of the glasses without Tm2O3 content show that the Urbach cutoff occurs at about 320 nm and, is relatively independent of the LiCl content. Six absorption bands were observed in the Tm2O3 doped glasses corresponding to the absorption of the 1G4, 3F2, 3F3 and 3F4, 3H5 and 3H4 levels from the 3H6 ground level of Tm3+ ions. The spectra also show that the integrated absorption cross-section of each band depends on the glass composition. Judd-Ofelt theory was used to determine the Judd-Ofelt parameters as well as the radiative transition probabilities for the metastable levels of Tm3+ ions in (0.3)LiCl + (0.7) TeO2: 0.01 Tm2O3 glass which is moisture-resistant. PMID- 11206562 TI - Surface enhanced fluorescence and Raman imaging of Langmuir-Blodgett azopolymer films. AB - The spectroscopic properties and surface-enhanced spectra of Langmuir-Blodgett (LB) films of methacrylic homopolymer (HPDR13) are presented. It is shown that LB film displays strong fluorescence attributed to the spatial restrictions imposed by its structure. The emission is observed in conjunction with photoisomerization, a process clearly demonstrated by the formation of surface relief gratings in the LB film [C.R. Mendonca et al., Macromolecules 32 (1999) 1493]. Surface-enhanced Raman scattering (SERS), Surface-enhanced resonance Raman scattering (SERRS) and surface-enhanced fluorescence (SEF) were observed for LB films of HPDR13 deposited onto silver island films. SERS measurements were also carried out on a sample fabricated with one monolayer LB film deposited onto silver islands followed by one overlayer of silver (LB sandwiched between two layers of silver islands). The polymer interacts very weakly with the metal surface (physisorption), and the enhancement effect is determined by the local electric field enhancement. The strong SERS and SERRS signals were suitable for micro-Raman imaging. Line, area mapping and global images of the LB monolayer on silver island are reported. The transfer ratio in the fabrication of the LB suggests a homogeneous coating of the silver islands, thereby the chemical images show the variation of the SERS intensity due to surface enhancement. PMID- 11206563 TI - An experimental and theoretical study of excited-state dipole moments of some flavones using an efficient solvatochromic method based on the solvent polarity parameter, E(N)(T). AB - The electronic absorption and fluorescence spectra of some biologically active natural flavones have been recorded at room temperature (298 K) in solvents of different polarities. The effects of the solvents upon the spectral properties are discussed. Difference in fluorescence intensity of flavones has been explained on the basis of intersystem crossing and degree of non-planarity calculated theoretically using Austin Model 1 (AM1) method. Excited-state dipole moments have been determined using the solvatochromic method based on the microscopic solvent polarity parameter, E(N)(T). A reasonable agreement has been observed between experimental and AM1 calculated dipole moment changes. Our results are found to be quite reliable in view of the fact that the correlation of the solvatochromic Stokes shifts with microscopic solvent polarity parameter, E(N)(T) is superior to that obtained using bulk solvent polarity functions for all the systems studied here. PMID- 11206564 TI - Intramolecular excited-state proton-transfer studies on flavones in different environments. AB - The absorption and fluorescence spectra of some biologically active flavones have been studied as a function of the acidity (pH/H0) of the solution. Dissociation constants have been determined for the ground and first excited singlet states. The results are compared with those obtained from Forster-Weller calculations. The acidity constants obtained by fluorimetric titration method are in complete agreement (in most of the systems) with ground state data indicating a excited state deactivation prior to prototropic equilibration. Compared to umbelliferones, flavones are only weakly fluorescent in alkaline solution. This behaviour is explained by the small energy difference between the singlet excited state and triplet excited state giving rise to more efficient intersystem crossing. Most of the flavones studied here undergo adiabatic photodissociation in the singlet excited state indicating the formation of an exciplex or a phototautomer. PMID- 11206565 TI - Absorption spectroscopic study of EDA complexes of. AB - [70]Fullerene has been shown to form 1:1 molecular complexes with toluene, p xylene, m-xylene, 1,2,4,5-tetramethyl benzene (durene) and pentamethyl benzene (PMB) in CCl4 medium by absorption spectroscopic method. Isosbestic points have been detected in case of complexes with PMB and durene. Charge transfer absorption band could not be detected but the intensity of the broad absorption band of C70 in CCl4 decreases systematically with increase in the concentration of the added methylbenzenes. From this trend the formation constants (Kc) of the complexes have been determined at three different wavelengths. The constancy of Kc with respect to change in the wavelength of measurement supports the view that complex of a single stoichiometry (1:1) is formed in each case. PMID- 11206566 TI - Study of the adsorptive behavior of water-soluble dye molecules (rhodamine 6G) at the air-water interface using confocal fluorescence microscope. AB - A confocal fluorescence microscope was applied to directly study the characteristic behaviors of adsorbed molecules at the air-water interface for a water-soluble chromophore, rhodamine 6G (R6G), in its extremely low-concentration region (below 10(-10) M). Significant photon bursts were observed only from the surface, and their width, height, and frequency were found to depend on the bulk concentration, suggesting the inhomogeneous distribution of R6G molecules at the air-water interface. This property of the adsorbed molecules is different from that of the bulk one. The influence of the ionic strength on photon bursts from the interface was investigated. It was found that the addition of NaCl to the R6G solution caused a decrease of the fluorescence signal. A change in the size of the aggregate and in the fluorescence quantum yield of the adsorbed molecules was suggested to be responsible for this experimental result. PMID- 11206567 TI - Eigenvalues and principal component loadings of heavily overlapped vibrational spectra. AB - In order to illustrate the possibilities of principal component analysis in determining the number of components in a system of heavily overlapped spectra, several numerical spectral models were formed of bands with very close parameters. The models consisted of three bands, whose peak positions were locally shifted and noise added. For all the cases the relations between eigenvalues and principal component loadings were considered. It was shown that for those complex spectra for which peak positions and band halfwidths can be determined with high accuracy, eigenvalues criteria could easily indicate the number of components. For all analyzed models, the consideration of the shape of loadings was proven to have a high importance. In limited number of cases the shape of a loading can make the results of eigenvalue analysis more understandable. It has been shown that the noise can be treated as a main limitation in the application of the method to this type of the spectra. PMID- 11206568 TI - Vibrational overtone spectra of chloroanilines--evidence for intramolecular hydrogen bonding in o-chloroaniline. AB - The near infrared vibrational overtone absorption spectra of liquid phase aniline and chloroanilines are reported. The analysis of the observed CH and NH local mode mechanical frequency values shows that intramolecular hydrogen bonding occurs between NH2 group and chlorine atom in o-chloroaniline. This observation supports the conclusion drawn from microwave spectroscopic studies reported earlier. PMID- 11206569 TI - Spectrofluorimetric determination of Er (III) with diantipyrylmethane. AB - The optimum fluorescence conditions for erbium (III) are obtained by irradiating this lanthanide at 435 nm in 0.04 microg ml(-1) diantipyrylmethane solution at pH = 8 (lambdaem = 510 nm). The method proposed is satisfactory for the determination of erbium (III) in the range of 0.001 to 1 microg ml(-1). The relative standard deviation 0.02 microg ml(-1) Er (III) in 0.04 microg ml(-1) diantipyrylmethane solution is 1.1%. The effect of other rare earths upon the intensity of the fluorescence emitted by erbium (III) is discussed. PMID- 11206570 TI - Vibration and vibronic spectra of lanthanide compounds with different types of coordination polyhedra of tungsten and molybdenum. AB - Luminescence excitation vibronic spectra as well as IR and Raman spectra of about 50 primary, binary and ternary lanthanide tungstates and molybdates and compounds with mixed anions (doped by Eu3+ ions) relating to about 15 structural types were analysed. Correlation of the types of isolated and joint coordination polyhedra of tungsten or molybdenum with details of the vibration and Eu3+ vibronic spectra was investigated. PMID- 11206571 TI - Emission spectra studies on the hydrogen-bonding complexes between p-methoxy-2 styrylquinoline and acids. AB - The ground and excited state interactions between p-methoxy-2-styrylquinoline (2 StQ-OMe) and different protic acids with various acid concentrations were studied in different media. Emission bands due to the hydrogen bonding complex, protonation complex and aggregation or solid complex were observed for the first time, in n-hexane. The different reaction pathways were controlled by the solvent polarity and the concentrations of the protic acid. The acidity of acid was also important to the acid-base complex. PMID- 11206572 TI - Infrared evidence of NO linkage photoisomerization in Na2[Fe(CN)5NO].2H2O at low temperature: experimental and theoretical (DFT) isotopic shifts from 15n(O), 18O and 54Fe species. AB - Infrared spectra of the metastable state I (MSI) of normal and 15NO, N18O and 54Fe isotopically substituted sodium nitroprusside dihydrate (Na2[Fe(CN)5NO].2H2O) have been obtained at 77 K. A comparison of the isotopic shifts measured for the vibrational modes of the FeXY (XY = NO or ON) moiety with those calculated by means of quantum chemistry (DFT) procedures supports the linear Fe-O = N arrangement for the MSI state. PMID- 11206573 TI - Tautomerism and infrared spectra of 2-thiopurine: an experimental matrix isolation and theoretical ab initio and density functional theory study. AB - Infrared spectra of 2-thiopurine (2-mercaptopurine, 2-purinethiol ) isolated in low-temperature Ar and N2 matrixes are reported. These spectra indicate that the compound adopts exclusively the thiol N9H tautomeric form. The theoretical calculations of relative energies of 2-thiopurine tautomers have been carried out at the MP4(SDTQ)//HF level using the 6-31G(d,p) basis set. The thiol N9H tautomer was predicted to be the most stable of all isomers of 2-thiopurine. The infrared spectra of the tautomers of 2-thiopurine have been calculated at the DFT(B3LYP)/6 31G(d,p) level. Good agreement between the experimental spectra and the spectra calculated for thiol N9H tautomer supported the identification of the dominant tautomer. It has also allowed for the reliable assignment of the bands observed in the experimental IR spectrum. PMID- 11206574 TI - Study of properties on non-protected room temperature phosphorescence and delayed excimer fluorescence of pyrene solution. AB - A strong and stable room temperature phosphorescence (RTP) and delayed excimer fluorescence signal located at 596 and 475 nm, respectively, can be induced for pyrene solution in the absence of any protective medium only use KI or TlNO3 as a heavy atom perturber (HAP) and Na2SO3 as a deoxygenator. Both lifetimes of RTP and the delayed fluorescence are in the order of X-ms and the intensities are changed with kind and amount of HAP, but the peak positions are same and there is a iso-luminescent point in the emission spectra corresponding to emission at 475 nm and at 596 nm. The optimum conditions and the effects of kind and amount of HAP and organic solvents on luminescence properties of pyrene solution were studies in detail, and the photophysical process in the presence of KI or TlNO3 for phosphorescence and delayed excimer fluorescence emission of pyrene solution was discussed. PMID- 11206575 TI - An engineered lox sequence containing part of a long terminal repeat of HIV-1 permits Cre recombinase-mediated DNA excision. AB - In our previous report, one 34-bp sequence from a long terminal repeat (LTR) of human immunodeficiency virus type 1 (HIV-1) clone, loxLTR-1, was proposed as a target site for site-specific excision by modified Cre recombinase. To support this suggestion, an engineered lox sequence, designated loxIL1, was made. This variant lox has the corresponding sequence of loxLTR-1 at the spacer region and the last two bases of inverted repeat sequence. Through in vitro recombination assay, loxIL1 also allowed the wild-type Cre to specifically recombine the sequence. An in vitro DNA binding experiment with mutants CreK244R and CreK244L revealed that lysine 244 of Cre plays an important role in interaction with the engineered lox. This result suggests that loxLTR-1 would be a candidate for antiviral strategy using site-specific recombinase. PMID- 11206576 TI - Changes in lung-specific molecular expression during differentiation of hamster embryonic M3E3/C3 cell line. AB - To clarify the differentiation mechanisms of bronchiolar epithelial cells, changes at the transcription level of epithelial cell-specific proteins were examined using M3E3/C3, a cell line derived from hamster fetal lung. During a 9 day incubation period with 24 microg/mL of retinol, the cells became attached to each other and formed large bud-like structures which could be detected with periodic acid-Schiff staining. During the incubation period, the mRNA level of surfactant-associated protein-B significantly increased 2.6- and 5.4-fold higher than cells incubated without retinol on days 3 and 9, respectively. The Clara cell-specific secretory protein mRNA level also increased and peaked at 5.1-fold (P < 0.05) on day 5 compared with control cells. In contrast, mRNA for surfactant associated protein-C, an alveolar type II cell-specific protein, decreased. Moreover, the expression of the gene for hepatocyte nuclear factor 3alpha, a putative transactivating factor for lung-related genes, was up-regulated resulting in consistently higher levels (2.4- to 5.6-fold) compared with controls, while those for transmembrane-type mucin-1 and glyceraldehyde-3 phosphate dehydrogenase were constantly expressed during the incubation. The present study confirms that at the gene transcription level M3E3/C3 cells differentiate into Clara-like cells with mucus granules in the presence of retinol. PMID- 11206577 TI - Effect of oxidative stress on stability and structure of neurofilament proteins. AB - Neurofilament proteins are highly phosphorylated molecules in the axonal compartment of the adult nervous system. We report the structural analysis of neurofilament proteins after oxidative damage. SDS-PAGE, immunoblotting, circular dichroism, and Fourier transform infrared spectroscopy were used to investigate the relative sensitivity of neurofilaments to oxidative stress and to identify changes in their molecular organization. An ascorbate-Fe+3-O2 buffer system as well as catechols were used to generate free radicals on a substrate of phosphorylated and dephosphorylated neurofilaments. By Fourier Transform Infrared spectroscopy and circular dichroism, we established that the neurofilament secondary structure is mainly composed of alpha-helices and that after free radical damage of the peptide backbone of neurofilaments, those helices are partly modified into beta-sheet and random coil structures. These characteristic reorganizations of the neurofilament structure after oxidative exposure suggest that free radical activity might play an important role in the biogenesis of the cytoplasmic inclusions found in several neurodegenerative diseases. PMID- 11206578 TI - The interaction of ferrocytochrome c with long-chain fatty acids and their CoA and carnitine esters. AB - Non-covalent modification of cytochrome c may have implications for electron transport and energy metabolism. We examined the interaction of various fatty acids (FAs), their coenzyme A and carnitine esters, and fatty alcohols with horse heart ferrocytochrome c. A comparison of FAs indicated a minimum chain length of 14 carbons was required for significant effect on the ferroheme chromophore and major changes in electronic spectra. Coenzyme A and carnitine esters interacted less strongly than FAs whereas long-chain alcohols did not interact with the protein. We found a single, saturable FA binding site with Kd (oleate) of 23.1 microM (by stopped-flow kinetics), 30 microM (by radiochemical binding assay), and 29 microM (by spectrophotometric assay). The binding stoichiometry was 1:1. We present evidence from electronic spectra, and proton NMR (nuclear magnetic resonance) that the S-Fe coordination (methionine 80) was disrupted by ligand binding. From molecular modeling we identify a putative binding channel flanked by lysines 72 and 73. PMID- 11206579 TI - A comparative hybridization analysis of yeast DNA with Paramecium parafusin- and different phosphoglucomutase-specific probes. AB - Molecular probes designed for the parafusin (PFUS), the Paramecium exocytic sensitive phosphoglycoprotein, gave distinct hybridization patterns in Saccharomyces cerevisiae genomic DNA when compared with different phosphoglucomutase specific probes. These include two probes identical to segments of yeast phosphoglucomutase (PGM) genes 1 and 2. Neither of the PGM probes revealed the 7.4 and 5.9 kb fragments in Bgl II-cut yeast DNA digest detected with the 1.6 kb cloned PFUS cDNA and oligonucleotide constructed to the PFUS region (insertion 3--I-3) not found in other species. PCR amplification with PFUS-specific primers generated yeast DNA-species of the predicted molecular size which hybridized to the I-3 probe. A search of the yeast genome database produced an unassigned nucleotide sequence that showed 55% identity to parafusin gene and 37% identity to PGM2 (the major isoform of yeast phosphoglucomutase) within the amplified region. PMID- 11206580 TI - Antioxidant activity levels and oxidative stress as blood markers of allergic response to drugs. AB - Antioxidant enzymes work together in human blood cells against toxic reactive oxygen species. Although their relationship with several pathophysiologic processes has been stated, not much is known about the connection between antioxidant defence and allergy. This study was designed to determine the enzymatic activities and the oxidative indices in the blood and serum proteins in patients suffering from allergy to drugs. We hypothesize that serum and blood reactions may serve as useful clinical marker for the allergic state. We used enzymatic antioxidant activities, thiobarbituric acid reactive substances, and carbonyl contents of proteins as suitable markers. We determined superoxide dismutases, glutathione peroxidase and catalase activities in each cell type. After antihistaminics plus steroids were given as part of a protocol treatment, enzymatic antioxidant activities, thiobarbituric acid reactive substance levels, and carbonyl contents were used as recovering markers for the disease. We found a relationship between antioxidant enzymatic activities, thiobarbituric acid reactive substance levels, and carbonyl contents for allergic reactions belonging to several type I and type IV allergies, as well as cross-reactive intolerance to nonsteroidal anti-inflammatory drugs and an anaphylactoid reaction to a radiocontrast media. A similar pattern also exists for analogous allergic manifestations and disease-like status. PMID- 11206581 TI - Flammulin: a novel ribosome-inactivating protein from fruiting bodies of the winter mushroom Flammulina velutipes. AB - A protein with a molecular weight of 40 kDa, capable of inhibiting cell-free translation in a rabbit reticulocyte lysate system with an IC50 of 0.25 nM, was isolated from fruiting bodies of the mushroom Flammulina velutipes. The protein, designated flammulin, was devoid of ribonuclease activity. Flammulin was unadsorbed on DEAE-cellulose at neutral pH and low ionic strength and adsorbed on CM-Sepharose and Affi-gel blue gel under similar conditions. Its N-terminal sequence demonstrates sites of similarity to those of plant ribosome-inactivating proteins (RIPs). PMID- 11206582 TI - The chicken stathmin gene and its expression in the embryo. AB - Stathmin, which functions as an intracellular relay in signal transduction pathways, has been suggested as a potential indicator of pluripotent cells in the early mouse embryo. In this study, chicken stathmin cDNA and genomic DNA were analyzed. In mammals stathmin consists of five exons and four introns; exons 3, 4, and 5 in the mammalian stathmin gene are equivalent to one relatively large exon in the chicken stathmin gene. Introns equivalent to introns 3 and 4 in the mammalian stathmin gene are not present in the counterpart gene in chickens and, although intron 2 was shown to be present in both mammals and birds, it is smaller in the chicken stathmin gene. Despite differences in the genomic organization of the gene and its smaller size in chickens compared with that in humans and mice, similarities in the coding sequences and in the expression of the chicken and mouse stathmin genes at certain stages of embryo development, as determined by whole-mount in situ hybridization experiments, suggest that their products are functional homologues. The argument is thus substantiated for further investigations into the use of regulatory regions of the stathmin gene in a system for the establishment of long-term cultures of germline competent chicken embryonic stem (ES) cells by the selective ablation of differentiated cells in culture using drug selection. PMID- 11206583 TI - Tamoxifen inhibits phorbol ester stimulated osteoclastic bone resorption: an effect mediated by calmodulin. AB - Tamoxifen inhibits bone resorption by disrupting calmodulin-dependent processes. Since tamoxifen inhibits protein kinase C in other cells, we compared the effects of tamoxifen and the phorbol ester, phorbol myristate acetate, on osteoclast activity. Phorbol esters stimulate bone resorption and calmodulin levels four fold (k0.5 = 0.1-0.3 microM). In contrast, tamoxifen inhibited osteoclast activity approximately 60% with an IC50 of 1.5 microM, had no apparent effect on protein kinase C activity in whole-cell lysates, and reduced protein kinase C alpha recovered by immunoprecipitation 75%. Phorbol esters stimulated resorption in a time-dependent manner that was closely correlated with a similar-fold increase in calmodulin. Protein kinase C alpha, beta, delta, epsilon, and zeta were all down-regulated in response to phorbol ester treatment. Tamoxifen and trifluoperazine inhibited PMA-dependent increases in bone resorption and calmodulin by 85 +/- 10%. Down-regulation of protein kinase C isoforms by phorbol esters suggests that the observed increases in bone resorption and calmodulin levels are most likely due to a mechanism independent of protein kinase C and dependent on calmodulin. In conclusion, the data suggest that protein kinase C negatively regulates calmodulin expression and support the hypothesis that the effects of both phorbol esters and tamoxifen on osteoclast activity is mediated by calmodulin. PMID- 11206584 TI - Glycine cleavage enzyme complex: rabbit H-protein cDNA sequence analysis and comparison to human, cow, and chicken. AB - The H-protein is one of the four essential components (H-, L-, P-, and T proteins) of the mammalian glycine cleavage enzyme complex, the major degradative pathway of glycine. We have isolated the full-length cDNA of the H-protein gene from the rabbit (Oryctolagus caniculus) by reverse transcription of liver poly-A mRNA and determined its nucleotide sequence (GenBank Acc. No. BankIt 31828 PMID- 11206585 TI - Diagnostic yield of the lactate stress test in 160 patients with suspected respiratory chain disorder. AB - Aim of the present study was to investigate the diagnostic yield of the lactate stress-test in unselected patients with suspected respiratory-chain disorder (RCD). Serum lactate was determined before, during and after a 15-minute, constant 30W workload on a bicycle in 48 controls and 160 patients with suspected RCD. 122 had definite RCD, 38 neurological disorders other than RCD. The sensitivity, specificity, positive predictive value, negative predictive value and pre-test likelihood of the test was 69, 74, 89, 42 and 76% respectively. In conclusion, the lactate-stress-test proved a powerful tool to assess impaired oxidative metabolism in RCDs. PMID- 11206586 TI - Altered striatal dopamine D2 receptor density and dopamine transport in a patient with hepatic encephalopathy. AB - A patient suffering from liver cirrhosis presented with a bradykinetic-rigid syndrome suspected as Parkinson's disease. A detailed work-up of the case revealed hepatic encephalopathy as the cause of the neurological symptomatology. An alteration of striatal dopamine D2 receptor binding and dopamine re-uptake sites was demonstrated by 123I-iodobenzamide (IBZM) and 123I-beta-CIT single photon emission computed tomography (SPECT), respectively. It is suggested that the alteration of the dopamine re-uptake in cirrhotics may be the cause of an increased catabolism of dopamine in HE. PMID- 11206587 TI - Visual event-related potentials in cirrhotic patients without overt encephalopathy. AB - Ambulant patients with cirrhosis and no clinical evidence of encephalopathy were screened for impaired brain function by neuroelectrophysiological testing dependent on cognitive function. Infrequent large checkerboard visual stimuli were randomly interleaved with frequent small ones to elicit P300 event-related potentials (ERPs). Three ERP components, N200, P3a and P3b, were derived from the electroencephalogram (EEG) by computer averaging. The use of 10% contrast and a minimum of four precisely placed scalp electrodes were found to be necessary for optimal separation of ERPs from sensory evoked potentials. Visual ERPs, onset/offset and pattern-reversal visual evoked potentials (VEPs), the spontaneous EEG and the time taken to complete a standard number connection test (NCT) were obtained from 20 normal adult subjects and 19 age-matched patients with histologically-confirmed cirrhosis and no clinical evidence encephalopathy. The latencies and amplitudes of evoked potentials and the alpha rhythm of the EEG were determined. In 6 of the 19 patients the latencies of P3a and/or P3b exceeded the corresponding mean for controls + 2 standard deviations of that mean. In 4 other patients the NCT was prolonged. In all of the patients the N200, VEPs and alpha rhythm of the EEG were normal. IN CONCLUSION: (i) Optimal isolation of ERPs is critically dependent on stimulus contrast and electrode placement; (ii) ERPs appear to be more sensitive than primary sensory evoked potentials or the EEG in detecting impaired brain neuroelectrophysiological function; and (iii) Cirrhotic patients without overt encephalopathy in whom P3a and/or P3b latencies are prolonged may have subclinical hepatic encephalopathy. PMID- 11206588 TI - Protective effect of riluzole on MPTP-induced depletion of dopamine and its metabolite content in mice. AB - The neuroprotective effects of riluzole (2-amino-6-trifluoromethoxy benzothiazole), a Na+ channel blocker with antiglutamatergic activity, MK-801, a blocker of N-methyl-D-aspartate (NMDA) receptors and monoamine oxidase (MAO) inhibitor pargyline were compared in the model of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-induced depletion of dopamine and its metabolite 3,4 dihydroxyphenylacetic acid (DOPAC) levels in mice. The mice received four intraperitoneal injections of MPTP (10 mg/kg) at 1-hr intervals and then the brains were analyzed at 1, 3 and 7 days after the treatments. Dopamine and DOPAC levels were significantly decreased in the striatum from 1 day after MPTP treatments. A severe depletion in dopamine and DOPAC levels was found in the striatum 3 and 7 days after MPTP treatments. Riluzole dose-dependently antagonized the MPTP-induced decrease in dopamine and DOPAC levels in the striatum. Pargyline also protected against MPTP-induced decrease in dopamine levels in the striatum. However, this drug showed no significant change in the striatal DOPAC levels. On the other hand, MK-801 failed to protect against MPTP induced decrease in dopamine levels in the striatum. However, MK-801 reversed the MPTP-induced decrease in DOPAC levels. These results suggest that riluzole can protect against MPTP-induced striatal dopamine and DOPAC depletion in mice. This protective effect may be caused by inactivation of voltage-dependent Na+ channels by riluzole. Furthermore, the present study suggests that the activation of NMDA receptors does not mainly contribute to MPTP-induced neurodegeneration, whereas MAO, especially MAO type B(MAO-B) plays a crucial role in MPTP-induced degeneration of the nigrostriatal dopaminergic neuronal pathway. PMID- 11206589 TI - Cyanide-induced free radical production and lipid peroxidation in rat brain homogenate is reduced by aspirin. AB - The neuroprotective properties of aspirin were investigated using cyanide-induced neurotoxicity as model. Cyanide, a known neurotoxic agent significantly increased lipid peroxidation and superoxide anion levels in rat brain homogenate in a concentration-dependent manner (0.25-1.0 mM). When homogenate, containing 1.0 mM KCN was co-treated with aspirin (1.0 mM) there was a significant decrease in lipid peroxidation. Aspirin (0.5 mM and 1.0 mM) also significantly reduced KCN induced superoxide anion generation. The results of the present report therefore indicate a neuroprotective role for aspirin. PMID- 11206591 TI - Intracellular pH measurements of the whole head and the basal ganglia in chronic liver disease: a phosphorus-31 MR spectroscopy study. AB - The purpose of this study was to determine the intracellular pH of the whole head and in voxels localized to the basal ganglia in patients with chronic liver disease using phosphorus-31 magnetic resonance spectroscopy (31P MRS). The study group compromised 82 patients with biopsy-proven cirrhosis (43 Child's grade A, 25 Child's grade B and 14 Child's grade C). Eleven subjects showed no evidence of neuropsychiatric impairment on clinical, psychometric and electrophysiological testing, 37 showed evidence of minimal hepatic encephalopathy and 34 had overt hepatic encephalopathy. Unlocalized 31P MRS of the whole head was performed in 48 patients and 10 healthy volunteers. Localized 31P MRS of the basal ganglia was performed in the 34 patients and in 20 healthy volunteers. The intracellular pH values were calculated from the chemical shift difference between the inorganic phosphate (P) and phosphocreatine (PCr) resonances. The percentage inorganic phosphate (%Pi), phosphocreatine (%PCr) and betaNTP signals, relative to the total 31P signal, and peak area ratios of inorganic phosphate and phosphocreatine, relative to betaNTP were also measured. There were no differences between patients and volunteers in intracellular pH in 31P MR spectra measured from the whole head or the basal ganglia. There was no correlation between the severity of encephalopathy (West Haven criteria) or liver dysfunction (Child score) and intracellular pH values. There was also no significant change in the inorganic phosphate, phosphocreatine or betaNTP resonances in spectra acquired from the whole head. However, in spectra localized to the basal ganglia, there was a significant increase in mean P/NTP (p=0.02) and PCr/NTP (p=0.009). The mean %Pi and mean %PCr were also increased (p=0.06; p=0.05, respectively), but there was no significant change in mean %betaNTP. When the patient population was classified according to the severity of encephalopathy, those with overt disease had a higher mean P/NTP and %Pi (p=0.03; p=0.01), compared to the reference population. Our results suggest that there are detectable bioenergetic abnormalities in patients with minimal hepatic encephalopathy or stable, overt chronic hepatic encephalopathy, but any associated intracellular pH change is probably a secondary, rather than a primary phenomenon. PMID- 11206590 TI - Glucose transporters and glucose utilization in rat brain after acute ethanol administration. AB - In the normal adult brain, glucose provides 90% of the energy requirements as well as substrate for nucleic acid and lipid synthesis. In the present study, effects of ethanol on glucose transporters (GLUT) and glucose utilization were examined in rat brain. Male Sprague-Dawley rats weighing 250-300 gms were given either ethanol 3 gm/kg BW or saline i.p. 4 hrs prior to the animal sacrifice and removal of the cerebral cortical tissue. The cortical plasma membranes analyzed by cytochalasin B binding assay showed a decrease in GLUT number but not in GLUT affinity in the ethanol treated rats as compared to the control rats. The estimated Ro values were 70 +/- 8.9 Vs 91 +/- 8.9 pmoles/mg protein (p < 0.05 N=4) and the estimated Kd values were 0.37 +/- 0.03 and 0.28 +/- 0.05 microM (p: NS) in ethanol and control experiments respectively. Immunoblots of purified cerebral plasma membranes and low density microsomal fraction showed 17% and 71% decrease for GLUTI and 54% and 21% (p<0.05 or less; n=6) for GLUT3 respectively in ethanol treated rats than in control animals. Immunofluoresence studies also showed reduction of GLUT1 immunoreactively in choroid plexus and cortical microvessels of ethanol treated rats as compared to control rats. The effect of ethanol on regional cerebral metabolic rates for glucose (CMR(Glc)) was studied using [6-(14)C] glucose and showed statistically insignificant decrease in brain glucose utilization. These data suggest that ethanol in-vivo decrease GLUT number and protein content in rat cerebral cortex. PMID- 11206592 TI - New drug discovery in the postgenomic era: from genomics to proteomics. AB - We have entered an exciting new era in which the nearly completed mapping of the human genome is now leading to the ability to characterize the human proteome, thereby expanding the horizon for new drug development by 3 orders of magnitude. Figuring out which proteins are involved in which disorders and in which individuals with any given disorder holds the promise of highly individualized therapeutics in the not so distant future. PMID- 11206593 TI - Citalopram therapy for depression: a review of 10 years of European experience and data from U.S. clinical trials. AB - BACKGROUND: This review summarizes and evaluates clinical experience with citalopram, the latest selective serotonin reuptake inhibitor (SSRI) to be approved for the treatment of depression in the United States. DATA SOURCES: Published reports of randomized, double-blind, controlled clinical studies of citalopram were retrieved using a MEDLINE literature search. Search terms included citalopram, SSRI, TCA (tricylic antidepressant), depression, and clinical. For each study, data on antidepressant efficacy and adverse events were evaluated. Pharmacokinetic studies and case reports were reviewed to supplement the evaluation of citalopram's safety and tolerability. Data presented at major medical conferences and published in abstract form also were reviewed. STUDY FINDINGS: Thirty randomized, double-blind, controlled studies of the antidepressant efficacy of citalopram were located and reviewed. In 11 studies, citalopram was compared with placebo (1 of these studies also included comparison with another SSRI). In 4 additional studies, the efficacy of citalopram in preventing depression relapse or recurrence was investigated. In another 11 studies (including 1 meta-analysis of published and unpublished trials), citalopram was compared with tricyclic and tetracyclic antidepressants. Finally, results are available from 4 studies in which citalopram was compared with other SSRIs. A placebo-controlled study of citalopram for the treatment of panic disorder was reviewed for data on long-term adverse events. CONCLUSION: Data published over the last decade suggest that citalopram is (1) superior to placebo in the treatment of depression, (2) has efficacy similar to that of the tricyclic and tetracyclic antidepressants and to other SSRIs, and (3) is safe and well tolerated in the therapeutic dose range of 20 to 60 mg/day. Distinct from some other agents in its class, citalopram exhibits linear pharmacokinetics and minimal drug interaction potential. These features make citalopram an attractive agent for the treatment of depression, especially among the elderly and patients with comorbid illness. PMID- 11206594 TI - Safety and tolerability of a rapidly escalating dose-loading regimen for risperidone. AB - BACKGROUND: Risperidone is an "atypical" antipsychotic with strong binding affinity for dopamine-2 and serotonin-2 receptors. Risperidone is often used to treat hospitalized patients who have acute psychotic decompensation, and the therapeutic target dose commonly used is 2 to 6 mg/day. The most common clinical practice is to titrate the dose of risperidone to the target therapeutic dose over several days. This study investigated the safety and tolerability of a rapid oral-loading regimen for risperidone developed to achieve therapeutic doses of this antipsychotic within 24 hours. METHOD: Rapid-loaded risperidone was initiated with 1 mg. Subsequent doses were increased by 1 mg every 6 to 8 hours up to 3 mg. Dose increases were contingent on tolerance of last administered dose. RESULTS: Of a sample of 11 consecutive inpatients admitted to an acute psychiatric facility who were treated with this protocol, 7 tolerated the most rapid titration, achieving a standing dose of 3 mg b.i.d. in 16 hours. Three required a slightly slower titration and achieved this target dose in 24 hours. One patient could not tolerate the 3-mg dose but tolerated a standing regimen of 2 mg t.i.d. No patient experienced serious extrapyramidal side effects, sedation, or any other adverse event during the rapid titration, and in no case did risperidone have to be discontinued. CONCLUSION: These results suggest that aggressive dosing of risperidone is well tolerated in most psychiatric inpatients. PMID- 11206595 TI - Switching clozapine responders to olanzapine. AB - BACKGROUND: Clozapine is an atypical antipsychotic indicated for the management of severely ill patients with schizophrenia who have failed to respond adequately to standard drug treatment. The significant risk of agranulocytosis and seizure associated with clozapine has led to the restrictions in its use. Additionally, drug-induced sedation, sialorrhea, enuresis, and weight gain are often cited as problematic consequences of clozapine treatment. Our primary objective was to determine the effectiveness and safety of a method of slow cross-titration from clozapine to olanzapine among patients responsive to clozapine treatment but experiencing medication-induced adverse events. METHOD: Changes in symptomatology, mood, subjective response, and safety were examined in 20 outpatients meeting DSM-IV criteria for schizophrenia or schizoaffective disorder who converted from clozapine to olanzapine. Patients were considered clozapine responsive as evidenced by improved social function and decreased symptoms with clozapine therapy; however, they were interested in alternative pharmacologic treatment because of clozapine-related side effects. RESULTS: Equivalent efficacy of olanzapine to clozapine was found in 90% of the patients (18/20) in the study group, without rehospitalization or suicidal behavior in any of the patients. Also notable was a reduction in drug-induced side effects and improved subjective response to pharmacotherapy. CONCLUSION: The successful conversion from clozapine to olanzapine has the potential to provide great benefits for the patient, including reducing drug-induced side effects while maintaining symptom control. These preliminary results suggest that further research on converting clozapine responders to olanzapine is warranted. PMID- 11206596 TI - Divalproex sodium in substance abusers with mood disorder. AB - BACKGROUND: Substance abuse is a common comorbid illness in patients with mood disorders. Little has been written about the pharmacologic treatment of patients with affective lability and co-occurring substance abuse, however. The following report will describe clinical experience using divalproex sodium in substance abusing patients with mood disorder. METHOD: Twenty patients admitted to an intermediate-care inpatient substance abuse program were diagnosed with comorbid mood disorder (according to DSM-IV criteria) and treated with divalproex sodium in an open-label, naturalistic trial with no blind. All patients were followed clinically and were assessed using the Clinical Global Impressions scale (CGI) and laboratory studies. RESULTS: Seven patients referred while on divalproex treatment continued to exhibit improved mood. Eleven others had at least 1 week of follow-up, and 10 of these also showed improvement. In 13 cases, divalproex was used safely with other psychiatric medications. Two patients complained of slight tremor, 1 of whom was also taking fluoxetine. Fifteen of 17 patients in whom biochemistry and hematology laboratory studies were completed had unremarkable results; 2 other patients had pretreatment abnormalities, which worsened over the course of treatment. Mean plasma valproate level was 58.53 microg/mL. Mean length of follow-up was 38 days. Mean period of abstinence prior to starting medication was 48 days. Some patients reported decreased cravings, and, by self-report, all patients remained abstinent. CONCLUSION: This report suggests that divalproex sodium is efficacious and safe, both alone and in combination with other psychiatric medications, in treating substance-abusing patients with mood disorder. PMID- 11206597 TI - Sertraline treatment of panic disorder: response in patients at risk for poor outcome. AB - BACKGROUND: More than one third of panic disorder patients have a chronic and/or recurrent form of the disorder, accounting for much of the individual and societal cost associated with the illness. Six clinical variables have been most consistently identified as high-risk predictors of poor outcome: (1) panic severity, (2) presence of agoraphobia, (3) comorbid depression, (4) comorbid personality disorder, (5) duration of illness, and (6) female sex. No published research has systematically examined the differential antipanic efficacy of selective serotonin reuptake inhibitors in patients at high risk for poor outcome. METHOD: Data were pooled (N = 664) from 4 double-blind, placebo controlled studies of the efficacy of sertraline for the treatment of DSM-III-R panic disorder. Two of the studies were 12-week fixed-dose studies with starting daily doses of sertraline, 50 mg, and 2 were 10-week flexible-dose studies with starting daily doses of sertraline, 25 mg. All other study design features were the same, except for the exclusion of women of childbearing potential in the 2 fixed-dose studies. Exclusion of patients with marked personality disorders and depression meant that only 4 of the poor-outcome variables could be evaluated. RESULTS: Clinical improvement was similar for patients treated with sertraline whether or not they carried an agoraphobia diagnosis, had a duration of illness > 2 years, or were female. Patients with high baseline panic severity had significantly (p = .01) less improvement on the endpoint Clinical Global Impressions-Improvement (CGI-I) scale than patients with moderate severity, although the Clinical Global Impressions-Severity of Illness scale change score was higher in the patients with high severity (-2.00 vs. -1.31). For patients with 3 or more high-risk variables, there was a modest, but statistically significant, tendency for reduced global improvement (endpoint CGI-I score of 2.7 for the high-risk vs. 2.4 for the non-high-risk group; p = .017), although the high-risk group actually had a similar endpoint reduction in frequency of panic attacks (82%) compared with the non-high-risk group (78%). CONCLUSION: Treatment of panic disorder with sertraline was generally effective, even in the presence of baseline clinical variables that have been associated with poor treatment response. The main limitations of the analysis were the reliance on pooled data from 4 studies (even if the designs were similar) and our inability to examine the impact of depression and personality disorders on response to treatment because of the exclusion criteria of the clinical trials. PMID- 11206598 TI - Patient compliance to a new enteric-coated weekly formulation of fluoxetine during continuation treatment of major depressive disorder. AB - BACKGROUND: A new formulation of enteric-coated fluoxetine given once weekly could be a useful option for the long-term treatment of depression, but compliance to once-weekly fluoxetine treatment has not been assessed. METHOD: Patients were adults from the United Kingdom who had responded to fluoxetine treatment for a current episode of depression (DSM-IV criteria). In the baseline assessment phase, all patients (N = 117) were continued on 20 mg of open-label fluoxetine once daily for 4 weeks. In the follow-up phase, patients (N = 109) were randomly assigned to once-weekly or once-daily fluoxetine for 3 months. Patient compliance was monitored by electronic devices during both phases of the study. RESULTS: Compliance to once-weekly fluoxetine treatment was higher than compliance to once-daily fluoxetine (85.9% vs. 79.4%, respectively). CONCLUSION: Once-weekly fluoxetine treatment allows for new flexibility for both the clinician and the patient, and this study alleviates the concern that patients will forget weekly doses. PMID- 11206601 TI - Divalproex sodium for alcohol withdrawal and relapse prevention: a case report. PMID- 11206599 TI - Intramuscular ziprasidone compared with intramuscular haloperidol in the treatment of acute psychosis. Ziprasidone I.M. Study Group. AB - BACKGROUND: This 7-day, randomized, open-label, multicenter, international study compared the efficacy and tolerability of intramuscular (i.m.) ziprasidone with haloperidol i.m. and the transition from i.m. to oral treatment in hospitalized patients with acute psychotic agitation (related to DSM-III-R diagnoses). METHOD: Patients received up to 3 days of flexible-dose ziprasidone i.m. (N = 90) or haloperidol i.m. (N = 42) followed by oral treatment to day 7. After an initial ziprasidone i.m. dose of 10 mg, subsequent i.m. doses of 5 to 20 mg could be given every 4 to 6 hours (maximum daily dose = 80 mg) if needed, followed by oral ziprasidone, 80-200 mg/day. Haloperidol i.m. doses of 2.5 to 10 mg were given on entry, followed by 2.5 to 10 mg i.m. every 4 to 6 hours (maximum daily dose = 40 mg) if needed, then by oral haloperidol, 10-80 mg/day. RESULTS: The mean reductions in Brief Psychiatric Rating Scale (BPRS) total, BPRS agitation items, and Clinical Global Impressions-Severity scale scores were statistically significantly greater (p < .05, p < .01, and p < .01, respectively) after ziprasidone i.m. treatment compared with haloperidol i.m. treatment. Further reductions in these scores also occurred in both groups following transition to oral treatment. Ziprasidone was associated with a lower incidence of movement disorders and a reduced requirement for anticholinergic medication during both i.m. and oral treatment compared with haloperidol. Movement disorder scale scores improved with ziprasidone i.m. and oral treatment, but deteriorated with haloperidol. Other adverse events were rare with both treatments. CONCLUSION: Ziprasidone i.m. was significantly more effective in reducing the symptoms of acute psychosis and was better tolerated than haloperidol i.m., particularly in movement disorders. The transition from ziprasidone i.m. to oral ziprasidone was effective and well tolerated. PMID- 11206600 TI - Efficacy and response time to sertraline versus fluoxetine in the treatment of unipolar major depressive disorder. AB - BACKGROUND: Few studies have compared the treatment efficacy of the 2 selective serotonin reuptake inhibitors sertraline and fluoxetine. METHOD: A randomized, single-blind, parallel-group study of 10 weeks' duration comparing the efficacy of sertraline, 50 mg/day; sertraline, 100 mg/day; and fluoxetine, 20 mg/day, was conducted in 44 psychiatric outpatients with DSM-IV unipolar major depressive disorder. Antidepressant dosages were doubled at 6 weeks for subjects who had not achieved remission. Primary outcome measurements included the 21-item Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions Improvement scale (CGI-I), with scores of < or = 7 on the HAM-D and < or = 2 on the CGI-I representing a positive treatment response, i.e., remission. RESULTS: At 4 weeks, significant differences in rate of positive treatment response were noted, with 0% for sertraline, 50 mg; 46% for sertraline, 100 mg; and 31% for fluoxetine, 20 mg (p = .023). At 6 weeks, positive treatment response rates were 21%, 43%, and 31% for subjects taking 50 mg of sertraline, those taking 100 mg of sertraline, and those taking 20 mg of fluoxetine, respectively, with treatment groups no longer differing significantly from each other. In subjects for whom antidepressant dose was doubled at week 6, response rates at week 10 (4 weeks on increased dose) were 40% for sertraline, 100 mg; 43% for sertraline, 200 mg; and 55% for fluoxetine, 40 mg. CONCLUSION: Subjects taking sertraline, 100 mg, and fluoxetine, 20 mg, demonstrated an earlier treatment response compared with subjects taking sertraline, 50 mg. For patients without a positive response at 6 weeks, an increased antidepressant dose resulted in remission for a substantial proportion of patients when assessed 4 weeks later. PMID- 11206602 TI - The effectiveness of combining lithium with olanzapine in the treatment of resistant schizophrenia. PMID- 11206603 TI - Treatment of primary cranial dystonia (Meige's syndrome) with clozapine. PMID- 11206605 TI - Colon perforation and peritonitis associated with clozapine. PMID- 11206604 TI - Severe lithium toxicity induced by combined levofloxacin administration. PMID- 11206606 TI - Treatment of of koro with citalopram. PMID- 11206607 TI - The scourge of EPS: have atypical antipsychotics solved the problem? PMID- 11206608 TI - Heterogeneity of response to antipsychotics from multiple disorders in the schizophrenia spectrum. AB - BACKGROUND: Antipsychotic response after the initiation of neuroleptic treatment shows wide variation in schizophrenic patient populations. In this overview, the authors suggest that the variance in antipsychotic drug response within schizophrenia can be reduced by resolving the schizophrenias into several discrete "endophenotypes," each with different etiologic underpinnings. METHOD: Studies relating differences in the relative speed or completeness of antipsychotic response to differences in distribution of 2 biological markers with possible etiologic significance are reviewed. Such studies had assessed recently hospitalized, neuroleptic-free patients undergoing exacerbation of nonaffective psychotic disorders. Prior to initiation of neuroleptic, the cohort of patients had been assessed for the quantity of the dopamine metabolite homovanillic acid in plasma (pHVA) and had undergone the first of 2 magnetic resonance imaging (MRI) studies for analyses of ventricle volumes. A second MRI was subsequently performed during a period of (partial) remission to determine within-patient stability of ventricular volumes. These selected studies assessed the distribution of pHVA and distribution of rates of ventricular change, with non-normal distributions resolved by K-means clustering. The speed and completeness of neuroleptic-induced antipsychotic response were related to 3 clusters of patients delineated by modal distributions of pHVA and of apparent rates of ventricular change. RESULTS: At least 3 unique "endophenotypes" of the "group of the schizophrenias" can be defined with respect to speed and completeness of antipsychotic response. Each endophenotype appears to show at least one unique biological feature that differentiates it from a normal comparison group. A rapidly responsive psychosis was associated with excessive production of dopamine, as identifiable by elevation of pHVA and a "good prognosis" course. A delayed-response psychosis had low-to-normal pHVA, clinically demonstrated persistent negative symptoms, and was associated with an excessive rate of change in ventricle volume between exacerbations of psychosis and (partial) remissions. Finally, a nonresponsive psychosis could be characterized as having both low-to-normal pHVA and rate of change of ventricle volumes similar to that of controls. Additional studies revealed that each of the endophenotypes had high rates of the psychoses in family members. The good prognosis course of the rapidly responsive group of studied patients was also found in their family members who had psychotic disorders. Similarly, the prominent negative symptoms of the delayed-response probands were reflected as a prominent trait in their family members also afflicted with psychosis. The endophenotypes tended to "breed true" in terms of prognosis and negative symptoms. CONCLUSION: Major differences in antipsychotic response patterns appear to be associated with patient and family characteristics that may be related to differences in the etiology and consequent pathophysiology of illness. PMID- 11206609 TI - Simple nephrectomy: transperitoneal approach. AB - Transperitoneal laparoscopic nephrectomy is performed much as originally described by Clayman and associates, although preoperative embolization of the kidney is no longer routine. Some surgeons use a hand-assisted technique, especially in difficult cases or when the organ is being removed intact, as in live-donor nephrectomy. PMID- 11206610 TI - Simple nephrectomy: retroperitoneal approach. AB - Direct extraperitoneal surgery has become the preferred approach to laparoscopic nephrectomy since the introduction of the balloon dilation method. The lateral decubitus position provides good exposure, but the prone position is used at some centers to gain better exposure with the aid of gravity. The open conversion rate ranges from 0 to 16% and the complication rate from 5% to 45%, with most complications being minor. Retroperitoneal laparoscopic simple nephrectomy is definitely superior to open nephrectomy as judged by analgesic use and recovery time. The higher complication rate and lower efficiency can be taken care of by experience and proper case selection. PMID- 11206611 TI - Simple nephrectomy: hand-assisted technique. AB - Chronic inflammation or prior surgical procedures may complicate the laparoscopic performance of simple nephrectomy. In these difficult cases, hand-assisted laparoscopy may be useful. The position of the hand port depends on the particular situation, but the port must allow flexion of the wrist and access to the entire surgical field. The hand-assisted procedure is similar to standard laparoscopy in analgesic use, time to oral intake, length of stay, and time to full recovery. Hand-assisted laparoscopy allows the inexperienced surgeon to perform laparoscopy with the aid of tactile sensation and three-dimensional spatial orientation. For the experienced surgeon, the technique offers an alternative to open conversion when the laparoscopic procedure fails to progress. PMID- 11206612 TI - Simple nephrectomy: managing the difficult case: xanthogranulomatous pyelonephritis and autosomal dominant polycystic kidney disease. AB - Laparoscopic surgery for kidneys with xanthogranulomatous pyelonephritis or autosomal dominant polycystic disease has proved to be technically difficult but is possible. The Harmonic Scalpel facilitates the dissection of inflammatory tissues and does not inflict burns. Hand-assisted laparoscopy may be useful. Pain relief is obtained by most patients undergoing cyst drainage, although recurrence after a year or two is common. A specific and detailed preoperative diagnosis and treatment plan are essential to a successful outcome. PMID- 11206613 TI - Simultaneous bilateral simple nephrectomy. AB - Bilateral simultaneous nephrectomy is a rare procedure usually performed for end stage renal disease, most often because of persistent hypertension after renal transplantation. Four trocars generally are inserted, with a lower abdominal and a subcostal port being used by the surgeon. An intra-abdominal pressure of 8 to 10 mm Hg is used during the procedure. The first kidney is left in situ while the other one is being dissected. Unless there is infection or malignancy, a retrieval sac is not used. In our series of 13 cases, the operating times ranged from 240 to 390 minutes (mean 320 minutes), and the mean 125 mL. Surgical discharges criteria usually were met on postoperative day 1 or 2. Laparoscopic bilateral nephrectomy in a single session is feasible in nearly all properly selected cases, even in patients with previous abdominal surgery or peritoneal dialysis. The operation takes longer than open surgery and may have a higher complication rate, but recovery is faster. PMID- 11206614 TI - Laparoscopic live donor nephrectomy: outcomes equivalent to open surgery. AB - A shortage of kidney donors has contributed to the interest in laparoscopic live donor nephrectomy. Three transperitoneal ports are used, as is an AESOP robot. To maintain urine flow, the donor is kept volume expanded during the procedure, and the pneumoperitoneum pressure is minimized. The most critical and hazardous part of the surgery is dissection of the renal artery and vein. Abundant periureteral tissue should be left to protect the blood supply. Harvest of the right kidney is more difficult. Placing the extraction incision in the right upper quadrant and using a Satinsky clamp instead of a stapling device at the origin of the renal vein will provide maximum venous length and help prevent postoperative thrombosis of the allograft. In the first 175 laparoscopic renal harvest procedures at Johns Hopkins, the complication rate was 14%, the rate of open conversion was 2%, and 3% of the patients required transfusions. These rates improved with experience. There was no significant difference in the performance of the allografts or the recovery of the recipients from what is seen after open kidney harvest. Wider acceptance of laparoscopic renal harvest will increase the number of donors and will be helped by development of methods and devices that shorten the learning curve. PMID- 11206615 TI - Approach to decortication of simple cysts and polycystic kidneys. AB - Laparoscopic excision and marsupialization of symptomatic of recurrent simple renal cysts is an alternative to open or percutaneous surgery. Such surgery may also be useful for pain relief in patients with autosomal dominant polycystic kidney disease (ADPKD). An occlusion balloon catheter is placed in the renal pelvis at the start of the procedure. Cysts are punctured, and the outer wall of the larger cysts is excised with care not to incise the renal parenchyma. In patients with ADPKD, it is important to mobilize the kidney completely, particularly the upper pole, to treat every visible cyst. A laparoscopic ultrasound probe is used to guide the unroofing of any large cysts within 5 to 10 mm of the renal surface. At the end of the procedure, the integrity of the collecting system is confirmed. Strict criteria must be used in selecting patients with simple cysts for laparoscopic marsupialization to minimize the incidence of unsuspected malignancy, and the cyst wall should be examined by frozen and permanent section. Long-term follow-up is needed to evaluate the effect of laparoscopic decompression in ADPKD. PMID- 11206616 TI - Laparoscopic surgery for renal urolithiasis: pyelolithotomy, caliceal diverticulectomy, and treatment of stones in a pelvic kidney. AB - Laparoscopic techniques may be considered for the uncommon patient in whom open stone surgery is considered. Stones in caliceal diverticula not accessible percutaneously may be approached transperitoneally. Pelvic stones in ectopic kidneys can be retrieved laparoscopically through a pyelotomy created with scissors or a knife. Percutaneous nephrolithotomy under laparoscopic guidance can be used if the stone extends beyond the renal pelvis. In the patient with difficult stone disease, laparoscopy does not replace other minimally invasive techniques but rather complements them. It should be the rare patient in the future who needs open surgery for stone removal regardless of its location or the presence of anatomic variants. PMID- 11206617 TI - Laparoscopic retroperitoneal renal biopsy. AB - Histologic information can be pivotal in making treatment decisions. Ultrasound guided percutaneous biopsy is the current standard, but if this procedure fails or is considered to be high risk, laparoscopic biopsy may be appropriate. A CT or ultrasound scan is obtained to determine whether there is any condition that would mandate biopsy of a particular kidney. The retroperitoneal space is entered with a visual obturator, and, after CO2 insufflation to 15 to 20 mm Hg, the space is enlarged initially by blunt dissection with the laparoscope. Two-tooth biopsy forceps are used to obtain tissue, and hemostasis is achieved with the argon beam coagulator with care to vent the increased pressure created by the flow of gas. Postoperatively, specific attention is given to blood pressure control. Hemorrhage is the most common serious complication, so any anticoagulation regimen must be reinstituted cautiously. PMID- 11206618 TI - Laparoendoscopic renal surgery in children. AB - Laparoscopic renal surgery in children has been slow to evolve, but further development is warranted. Dysplasia, obstruction, or reflux leading to nonfunction are the most common indications for nephrectomy. Partial nephrectomy and reconstructive surgery can also be performed laparoscopically. Both transperitoneal and retroperitoneal approaches can be used, with each having advantages and disadvantages. The future of pediatric laparoscopic renal surgery will be determined by technical and methodologic advances. PMID- 11206619 TI - Laparoscopic radical nephrectomy. AB - Although open nephrectomy is the standard of care for localized renal-cell carcinoma, the significant postoperative pain and lengthy convalescence have encouraged the use of laparoscopy, which can yield similar 2- to 5-year survival rates. Either a transperitoneal or a retroperitoneal approach may be used, and sometimes, they are combined. Generally, the technique is limited to tumors <10 cm, but larger tumors can be removed. Nitrous oxide is avoided as an anesthetic agent. The dissection follows accepted oncologic principles: in situ renal dissection within Gerota's fascia, early ligation of the renal vessels, and careful removal of the specimen to prevent tumor spillage. Dissection of the hilum is facilitated by a PEER retractor and an Endoholder. On average, patients having laparoscopic radical nephrectomy return to normal activities approximately 4.5 weeks sooner than those having open surgery, a fact not taken into account in cost analyses. Laparoscopic nephrectomy may offer a special benefit in patients with known metastatic disease, as interleukin-2 administration can be started a month earlier than after open surgery. There may also be immunologic benefits of minimally invasive v open surgery. The technique and instruments continue to evolve, and cost-effectiveness should continue to improve. PMID- 11206620 TI - Laparoscopic radical nephroureterectomy. AB - Because of the high rate of ipsilateral multifocal disease and the low incidence of contralateral disease, upper tract transitional-cell carcinoma has historically been treated with radical nephroureterectomy. This operation has been performed laparoscopically in many medical centers, with various techniques. The difficult concept has always been handling of the distal ureter and bladder cuff. A technique involving transvesical laparoscopy-assisted transurethral dissection with low pressure that mimics the open procedure is used at the Cleveland Clinic. The reported mean operative times range from 2.6 to 8.3 hours, with the longest time being reported from one of the earliest series. Although the cost of laparoscopic nephroureterctomy is higher than that of the open procedure by about 24%, this figure does not include the societal costs of the longer convalescence after the latter operation. Longer follow-up will be required to learn whether the laparoscopic method is as effective from an oncologic standpoint as open surgery. PMID- 11206621 TI - Laparoscopic partial nephrectomy and wedge resection. AB - Partial nephrectomy is a more challenging operation than radical or simple nephrectomy, primarily because of the risk of complications such as bleeding. This problem is even more troublesome with minimally invasive approaches because of the dearth of effective hemostatic instruments and supplies. The location of the lesion determines whether a transperitoneal or a retroperitoneal route will be employed. Centrally located or anterior renal lesions generally are approached transperitoneally whereas peripheral lateral or posterior lesions are accessed by retroperitoneoscopy. The Harmonic Scalpel with slow cutting and high coagulation settings is useful for incising the renal capsule and parenchyma. The argon beam coagulator is helpful to stop any persistent bleeding. The few reported series of laparoscopic partial nephrectomy indicate considerably longer operative times than are needed for open surgery and hospitalization of upwards of 5 days, largely to monitor drainage and urine leakage. It is hoped that this advanced laparoscopic technique will become more user friendly with further developments in techniques and instrumentation to provide patients with the expected benefits of minimally invasive surgery. PMID- 11206622 TI - Laparoscopic cryoablation for renal-cell cancer. PMID- 11206623 TI - Laparoscopic nephropexy. AB - Although there has long been debate about the existence of nephroptosis, contemporary radiologic and biochemical studies confirm its existence. Both percutaneous and laparoscopic operations are available for fixing the kidney, with high early success rates. Objective documentation of the diagnosis is mandatory. Further studies with validated quality-of-life and pain questionnaires are needed to determine the long-term success of nephropexy. PMID- 11206624 TI - Laparoscopic Fenger plasty. AB - BACKGROUND: At our department, adults presenting with hydronephrosis secondary to short intrinsic stenoses of the ureteropelvic junction (UPJ) or ventrally crossing vessels are treated with laparoscopic nondismembered pyeloplasty. We herein present our long-term results. PATIENTS AND METHODS: From August 1994 to September 1999, 34 female and 31 male patients presenting with 67 obstructed UPJs underwent laparoscopic nondismembered pyeloplasty. The patients' ages ranged from 11 to 77 (mean 35.6) years. Preoperatively, all patients were evaluated with intravenous urography and isotope scans. In addition, color Doppler ultrasonography was performed to identify crossing vessels at the UPJ. Prior to surgery, a stent was placed, which was left indwelling until 6 weeks after surgery. On the right side, the transperitoneal and on the left, the retroperitoneal approach was used. Following dissection of the UPJ, the obstructing vessels were displaced. The stenosis of the UPJ was corrected by either Fenger plasty (63 UPJs) or Y-V plasty (4 UPJs). Postoperative evaluation included color Doppler ultrasonography, intravenous urography, and isotope studies. RESULTS: The mean operative time was 123 minutes. No intraoperative complications were seen. In 79% of the patients, ventrally crossing vessels were found and displaced from the UPJ. Forty-eight patients have been available for follow-up, which currently ranges from 4 to 60 (mean 25) months. In the most recent nine patients, the position of the crossing vessels relative to the UPJ was also assessed postoperatively by means of color Dopper ultrasonography. The mean distance of the vessels from the UPJ was 1.5 cm. There was a single failure, in a 19-year-old woman who presented with infected hydronephrosis. Laparoscopic nondismembered pyeloplasty failed because the stenosis, which was aggravated by the infection, was too long. The success rate thus was 98%. CONCLUSIONS: At our department, laparoscopic nondismembered pyeloplasty is the preferred method for the management of UPJ obstruction, while dismembered pyeloplasty is performed in rare cases only. PMID- 11206625 TI - Laparoscopic pyeloplasty. AB - Open pyeloplasty has long been considered the gold standard for the relief of ureteropelvic junction (UPJ) obstruction, but the incisional morbidity led urologists to explore less invasive alternatives such as endopyelotomy and the Acucise cutting balloon. Laparoscopic pyeloplasty was introduced in 1993 and has since been performed in patients as young as 2.5 years. The operation should be considered in patients with UPJ obstruction caused by a crossing vessel, high ureteral insertion, failed prior procedures, high-grade hydronephrosis, or marginal differential renal function. Hynes-Anderson, Foley Y-V, and Fenger procedures can all be performed laparoscopically, generally with excellent results. The procedure requires advanced laparoscopic skills and so is available in only a few medical centers at present. PMID- 11206626 TI - Retroperitoneoscopic and laparoscopic suturing: tips and strategies for improving efficiency. AB - BACKGROUND: The difficulties of minimally invasive reconstructive surgery, laparoscopically or retroperitoneoscopically, are caused by spatial limitation and fixed trocar positions and, therefore, restricted movement and handling of the instruments. In addition to a standardization of the technique, continual training, and improved instrument technologies, optimization of the geometry of reconstructive surgery, such as angles and distances between the working ports or the camera and needle position, are imperative to providing an optimal clinical performance. MATERIALS AND METHODS: After designing a standardized suturing technique and conducting an experimental analysis of the geometric factors important in reconstructive surgery, we transferred these results to our clinical setting. A series of 116 reconstructive laparoscopic and retroperitoneoscopic procedures (nephropexy, pyeloplasty, bladder neck suspension, and radical prostatectomy) were analyzed according to the technical realization and quality of reconstruction. Trocar and table positions were adjusted according to our preliminary results, as were the position of the instruments and camera. RESULTS: The trocar and instrument positions are critical for the clinical outcome of reconstructive surgery. Continual training in a standardized suturing technique, together with the clinical application of the important geometric rules, can reduce surgery time by 50%. The time required for suturing single knots could be decreased even more: as much as 75%, thus ensuring efficient and safe reconstructive surgery. CONCLUSION: Reconstructive procedures such as pyeloplasty or radical prostatectomy can be standardized and performed in an acceptable amount of time with adequate quality when adhering to a standardized technique and the important geometric rules. Improved performance in terms of time and quality will increase the acceptance of these procedures, which can help to solve the problem associated with a low total number of indications for laparoscopy and retroperitoneoscopy. PMID- 11206627 TI - Management of hemorrhage during laparoscopy. AB - Bleeding can be a complication of laparoscopic procedures commonly performed by urologists, such as pelvic node dissection and nephrectomy, and is often difficult to manage. Hemorrhage also can occur as a result of Veress needle or trocar placement, and there are specific strategies for the management of these injuries. Laparoscopic clip appliers, laparoscopic staplers, laparoscopic suturing, various energy sources (monopolar and bipolar electrocautery, laser, ultrasonic dissectors, and argon beam coagulators), and topical agents (gelatin foam, cellulose, collagen, and fibrin sealant) can be used to obtain hemostasis. Converting to laparotomy to obtain hemostasis may be necessary in some cases. Proper patient selection is important for lowering the risk of hemorrhage. PMID- 11206628 TI - Technical advances in laparoscopy: hand assistance, retractors, and the pneumodissector. AB - Technology is crucial to the laparoscopic surgeon. Reducing the technical difficulty of laparoscopic procedures is beneficial on many fronts: training is facilitated, operative time is reduced, and the practice of minimally invasive surgery can be further disseminated. Many advances in urologic laparoscopic surgery are attributable to the development of new operative instruments that reduce the technical difficulty. In this article, we highlight three technical advances in laparoscopy. Hand assistance can simplify many laparoscopic procedures. Because the surgeon retains tactile sensation, operative times are reduced compared with standard laparoscopic surgery, with minimal, if any, increase in patient morbidity. Other advances in instrumentation include various laparoscopic retractors and the Pneumodissector, a unique dissecting device. The breadth of retractors extends from reusable metal "fans" to disposable inflated "paddles," with many in between. The metal retractors may be more traumatic to delicate tissues than the inflatable ones but also are more versatile. The Pneumodissector facilitates tissue dissection by releasing short burst of carbon dioxide. It is a safe and effective instrument for blunt tissue dissection. These technical advances have contributed to the progression of laparoscopic urologic procedures. Technology will continue to have a significant impact on the advancement of laparoscopic urology and its potential widespread dissemination. PMID- 11206629 TI - Significance of the expression of p27Kip1 in esophageal squamous cell carcinomas. AB - Recent observations have demonstrated that the reduced expression of p27Kip1 (p27) is correlated with progression and poor prognosis of breast, colon, and gastric carcinomas. These observations led us to examine the expression of p27 and cyclin D1 and E protein in six esophageal carcinoma cell lines and 81 esophageal carcinoma tissues by Western blot analysis and immunohistochemistry. The expression levels of cyclin D1 and p27 were correlated clearly in esophageal carcinoma cell lines by Western blot analysis. Immunohistochemical analysis revealed that the high-grade expression of p27 protein was detected in 61% of esophageal carcinomas, and it was correlated with tumor invasion, lymph node metastasis, and poor patient prognosis. This observation was different from the results reported in other organs. Cell cycle regulation is a very complicated process. Homeostatic feedback mechanisms against the overexpression of cyclin D1 may exist in esophageal carcinomas, and there can be organ-specific regulations in the progression of carcinomas. PMID- 11206630 TI - Expression of p53, bcl-2, and bax as predictors of response to radiotherapy in esophageal cancer. AB - The sensitivity of cancers to radiotherapy or chemotherapy may be influenced by susceptibility to apoptosis. We evaluated whether expression of three proteins regulating apoptosis, p53, bcl-2, and bax, could predict the effect of radiotherapy in esophageal cancers. We used immunohistochemical staining for these protein regulators of apoptosis to study biopsy specimens obtained from 25 patients with esophageal squamous cell carcinoma before they underwent preoperative radiotherapy. Effectiveness of radiotherapy was assessed by barium esophagography, esophagoscopy, and computed tomography. Radiotherapy was effective in 12 patients and ineffective in 13 patients. Biopsy specimens from the 25 patients showed expression of p53, bcl-2, and bax to be 48.0%, 32.0%, and 76.0% respectively. Effectiveness of radiotherapy was correlated with p53 expression (p = 0.047), but bcl-2 and bax expression showed no relationship to effectiveness of radiotherapy. Expression of p53 protein in biopsy specimens may predict effectiveness of preoperative radiotherapy in esophageal cancers. PMID- 11206631 TI - Assessment of the predictive value of clinical and histopathological factors as well as the immunoexpression of p53 and bcl-2 proteins in response to preoperative chemotherapy for esophageal squamous cell carcinoma. AB - The aim of the study was to determine the predictive value of selected clinical and histopathological factors as well as the immunohistochemical expression of p53 and bcl-2 proteins in the prediction of the pathological response to preoperative chemotherapy in esophageal squamous cell carcinoma. Thirty-four patients with advanced squamous cell carcinoma of the thoracic esophagus (T2-4 N0 1 M0), who underwent one cycle of cisplatin and 5-fluorouracil therapy followed by subtotal esophagectomy, were studied. All clinical factors (tumor longitudinal diameter in a computed tomographic scan, invasion depth, the presence of lymph node metastasis and clinical tumor staging) were evaluated before the onset of the therapy. The histopathological features (grade of differentiation, degree of keratinization, nuclear polymorphism, mitotic index, pattern of cancer invasion and inflammatory response), and the expression of p53 and bcl-2 proteins were also estimated in prechemotherapy endoscopic biopsy specimens. Pathological response to chemotherapy was assessed in surgically resected specimens. Of 34 patients, two (5.9%) showed complete response (CR), six patients (17.6%) exhibited major histological changes (partial response 1; PR1), 24 (70.6%) showed minor histological changes (partial response 2; PR2), and two patients (5.9%) exhibited no response to chemotherapy (stable disease; SD). There were no significant relationships between the response to preoperative chemotherapy (CR + PR1 vs. PR2 + SD) and the majority of the clinical and all the histopathological features. Deeper cancer invasion before chemotherapy was the only factor that tended to worsen the therapy effect (p < 0.01). The pathological response to treatment had no significant associations with the expression of p53 and bcl-2 proteins in esophageal squamous cell carcinoma. It should be noted, however, that both patients in CR were p53 and bcl-2 protein-negative. PMID- 11206632 TI - Significance of lymph node dissection of the superior mediastinal region in esophageal cancer patients. AB - The effect of the superior mediastinal lymph node dissection was compared retrospectively with that of standard dissection in 108 esophageal cancer patients. Five-year survival rates were 46.3% in patients who underwent standard surgery (group A) and 39.3% in patients who underwent superior mediastinal lymph node dissection (group B). The survival curves were basically the same. Nineteen out of 42 (45.2%) tumors in group A and 24 out of 66 (36.4%) tumors in group B recurred. The distribution of the first sites of recurrence did not differ significantly between groups. However, 14 tumors (67%) in group A recurred in the lymph nodes, but only seven tumors recurred (28%) in the lymph nodes in group B. Eleven tumors (52%) in group A recurred to superior mediastinal nodes, but only one tumor (4%) recurred to a superior mediastinal node in group B. Fourteen of the group B patients showed metastasis to superior mediastinal lymph nodes and none of these patients survived for more than 5 years. Eleven of these 14 patients showed metastasis to only one or two nodes. Based on our data and other reported findings, we conclude that extended lymphadenectomy of the superior mediastinal region alone does not contribute to improved survival of esophageal cancer patients, but it does contribute to the prevention of lymph node recurrence in this region. PMID- 11206633 TI - Pyloroplasty in gastric replacement of the esophagus after esophagectomy: one layer or two-layer technique? AB - Pyloroplasty is our routine drainage procedure performed when the stomach is used as the esophageal substitute after esophageal resection for cancer. The technique of pyloroplasty varies among surgeons and effectiveness has not been studied. Thirty-four patients with a gastric conduit whose pyloroplasty was constructed with a one-layer technique (group 1) were compared with a historical cohort of 31 patients treated with a two-layer method (group 2). Patients who had an abnormal pyloroduodenal region were excluded from the study. Perioperative morbidity and post-operative gastrointestinal symptoms within the first 6 months were evaluated. Patient demographics and the types of surgical procedures did not differ between the two groups. The median daily output from the nasogastric tube was 119 mL in group 1 and 115 mL in group 2 (p = 0.49). In 40 out of 65 patients (62%), the nasogastric tube was removed at a median of 3 days after the operation in both groups. There was no leakage from the pylorus or the esophagogastric anastomosis in this study. In both groups, the patients could resume a semisolid diet at a median of 8 days after surgery. One patient in group 1 and two patients in group 2 developed gastroparesis clinically. No patient, however, required reoperation. There was no significant difference in cardiopulmonary complications attributable to the technique of pyloroplasty. The incidence of gastrointestinal symptoms within the first 6 months after surgery did not differ. Regurgitation was the most common symptom, affecting 10 patients in each group, 29% and 32% in group 1 and group 2 respectively (p = 1.0). Pyloroplasty was an effective gastric drainage procedure after esophagectomy whether the one or two-layer method was used. The authors prefer the one-layer method, which is safe and simple. PMID- 11206634 TI - Composite reconstruction of hypopharynx and esophagus. AB - Extended surgical resection of the whole esophagus and associated hypopharynx may require composite reconstructions using a combination of pediculated and free tissue units. Twelve patients were assigned to composite reconstructions of the hypopharynx and esophagus for either metachronous carcinoma of the esophagus and head and neck (group I, n = 4), cervical anastomotic recurrence of esophageal carcinoma (group II, n = 3), or secondary reconstruction after the failure of a previous reconstruction of hypopharynx or esophagus (group III, n = 5). Pediculated tissues were the stomach (n = 10), colon (n = 1), or jejunum (n = 1). A free jejunal graft was constantly interposed between the pharynx and the mobilized organ. There were no hospital deaths. Swallowing function was restored in all patients except one who had cervical leakage as a result of partial necrosis of the free jejunal graft. Composite reconstruction permitted, even in groups I and II in which prognosis was extremely poor, prolonged survival and oral feeding, which proved beneficial in terms of the patients' quality of life. PMID- 11206635 TI - Larynx preservation in surgical treatment of cervical esophageal cancer--combined procedure of laryngeal suspension and cricopharyngeal myotomy. AB - From July 1994 to July 1998, a larynx-preserving procedure was performed on 10 out of 22 (45%) patients in the surgical treatment of hypopharyngeal and cervical esophageal cancer. At first, all 10 patients were treated with concurrent radiochemotherapy with cisplatin (10 mg/m2/day), 5-fluorouracil (500 mg/m2/day) and radiation (2 Gy/day) five times per week for 4 weeks. After preoperative radiochemotherapy, the larynx-preserving procedure, combining laryngeal suspension and cricopharyngeal myotomy, was performed. The operative and hospital mortality rate was 0%. The incidence of post-operative morbidity with minor complications was 70% in the present study. Laryngeal speech and oral food intake were preserved in all patients after this procedure. The new larynx-preserving procedure combining laryngeal suspension and cricopharyngeal myotomy for cervical esophageal cancer is a favorable operative method for retaining intelligible laryngeal speech and good food intake. PMID- 11206636 TI - Late esophageal toxicity using a combination of external beam radiation, intraluminal brachytherapy and 5-fluorouracil infusion in carcinoma of the esophagus. AB - One hundred patients with potentially curable squamous cell carcinoma of the esophagus were treated using a combination of external beam radiation, medium dose intraluminal brachytherapy (ILBT), and 5-fluorouracil infusion (as a radiosensitizer) from January 1990 to December 1993. The main objective was to determine late toxicity and optimization of the dose of intraluminal radiation. All patients had external radiation of 50 Gy over 5 1/2 weeks, followed by ILBT of 20 Gy for 50 patients (group 1) and 15 Gy for a subsequent 50 patients (group 2), using a dose rate of 315-330 cGy/h with the prescription at 1 cm off axis. The 5-fluorouracil infusion was 500 mg/m2 administered 12 h prior to ILBT. The treatment-related complications among groups 1 and 2 were strictures 24% vs. 8% (p = 0.029), ulceration 30% vs. 28% (p = 0.8), and tracheoesophageal fistulae 12% for both groups. The overall survival for groups 1 and 2 was 8% and 23% at 5 years. The development of life-threatening complications is a major concern and extreme caution is urged before selecting patients for a combination of ILBT and 5-fluorouracil treatment. PMID- 11206637 TI - Multiple primary malignant neoplasms in patients with esophageal cancer. AB - This study aims to elucidate the incidence and the therapeutic and prognostic implications of co-existent non-esophageal primary malignant neoplasms in patients with esophageal cancer. Between 1974 and 1997, 33 patients with esophageal cancer treated at the Nippon Medical School Hospital were documented as having multiple primary malignant neoplasms (MPN). The therapeutic strategies and post-therapeutic survival of these patients were retrospectively investigated. Among 291 patients with esophageal cancer, 33 patients (11.3%) were also found to have non-esophageal primary malignant neoplasms. Twenty patients (60.6%) had synchronous MPN and 13 (39.4%) had metachronous MPN. Among the MPN, apart from esophageal cancer, gastric (32.6%) and head and neck cancer (32.6%) were the most common. The incidence of esophageal cancer occuring in association with cancers of the head and neck or gastric cancer was high. Frequent examination in these cancer patients, using fiberoptic esophagogastric endoscopy for example, may be helpful in the early diagnosis of esophageal cancer. PMID- 11206638 TI - Effect of clarithromycin on esophageal motility. AB - As clarithromycin (CLA), an antibiotic commonly used for Helicobacter pylori eradication, stimulates gastroduodenal motility, we investigated whether it also stimulates esophageal motility. In 15 normal subjects, esophageal motility was recorded using a low-compliance manometric system with two ports in the esophageal body, one port in the lower esophageal sphincter (LES), and five ports in the antroduodenal tract to monitor the occurrence of phases I-III of the migrating motor complex. Thirty minutes after the occurrence of a duodenal phase III, we infused intravenously, randomly, and in a double-blind manner, CLA 100 mg in five subjects (group A), CLA 250 mg in five subjects (group B), and normal saline in the remaining five subjects (group C). LES tone and post-deglutitive residual pressure, as well as the amplitude and duration of the esophageal contractions, were measured each minute and averaged over a post-infusion period of 30 min. Both group A and B showed a LES tone significantly higher than that of group C after CLA infusion, whereas the post-deglutitive residual pressure was not significantly different from that of group C. The LES tone of group B was significantly higher than that of group A. Group B, but not group A, showed a wave amplitude and duration significantly higher than that of group C. In conclusion, CLA is able to stimulate LES tone and esophageal contractions with a dose-related effect. PMID- 11206639 TI - Experimental evaluation of the safety and biocompatibility of a new antireflux prosthesis. AB - Previous studies have shown that encircling of the esophagogastric junction by a semiabsorbable scarf effectively prevents gastroesophageal reflux. The present study was performed to assess the long-term safety and biocompatibility of this type of scarf. The semiabsorbable scarf was implanted into 20 dogs either laparoscopically or via laparotomy. Pre- and post-operatively, contrast radiography, esophageal manometry, and upper gastrointestinal endoscopy were performed. No cases of perforation, stricture formation or other adverse effects were found after 1 and 2 years. It is concluded that the new type of scarf is without any adverse side-effects. Functional evaluation in reflux patients appears to be warranted. PMID- 11206640 TI - Long-segment substernal jejunal esophageal replacement with internal mammary vascular augmentation. AB - We describe a technique that uses the internal mammary vessels to enhance long segment jejunal graft blood supply in addition to an intact distal mesenteric vascular arcade. We believe that this technique, called vascular augmentation, improves jejunal graft perfusion and decreases ischemic complications. PMID- 11206641 TI - Gastric tube gastrectomy. AB - The incidence of esophageal adenocarcinoma has increased significantly in recent years. Early detection of a small mucosal tumor by endoscopy is occurring more frequently. This, together with improved results of surgical treatment, has created a new population of patients with prolonged post-esophagectomy survival. Adenocarcinoma in the reconstructed gastric tube is no longer a rare finding and is expected to be even more common in the future. We report a case of a patient treated for metachronous gastric tube carcinoma and discuss the steps of the surgical procedure. PMID- 11206642 TI - Squamous cell carcinoma in esophageal remnant after 24 years: lessons learnt from esophageal bypass surgery. AB - Cervical esophageal carcinoma has been a vexing problem because of the multicentric nature of the disease, the common advanced stage at presentation (with invasion of important adjacent structures, especially the trachea or larynx), and difficulty in satisfactorily reconstructing pharyngogastric continuity after extensive resection. In this case report, we highlight the complexity of managing squamous cell carcinoma of the cervical esophagus, which can reappear either as a new primary or recurrence, in a retained esophageal segment 24 years after esophageal bypass surgery. We strongly recommend total esophagectomy at the time of initial surgery and not 24 years later. PMID- 11206643 TI - Massive distension of the esophageal stump after cervical esophagogastrostomy in psychiatric patients. AB - We present two similar cases of huge distension of the esophageal stump after cervical esophagogastrostomy in two psychotic patients. Chronic use of anti psychotic drugs, in combination with prolonged mild anastomotic stricture, may have contributed to this situation. PMID- 11206645 TI - Radiation-induced esophageal squamous cell carcinoma in situ. AB - A report of radiation-induced squamous cell carcinoma in situ of the esophagus is presented. This report indicates that the patient developed the carcinoma in situ many years after chest wall irradiation for breast cancer treatment. A review of the literature with respect to carcinogenesis after radiotherapy is included and recommendations for the follow-up of patients having mediastinal radiation are suggested. PMID- 11206644 TI - Skin tube esophagus: present indications and late malignization. AB - If there is no other possibility for the replacement of the whole esophagus, skin tube esophageal reconstruction gives a good result. Three successful cases treated with the antethoracal neoesophagus formed from musculocutaneous flaps are discussed. All patients recovered successfully. However, there exists the possibility of late malignization in the skin tube esophagus. Two such cases are also presented. PMID- 11206646 TI - Long-term survivors after the resection of limited esophageal small cell carcinoma. AB - Patients with small cell carcinoma of the esophagus have a poor prognosis and have generally been treated by chemotherapy. However, all reported cases were at advanced stages. We need to establish an adequate treatment for patients with small cell carcinoma of the esophagus with invasion limited to the submucosal layer. In this paper, five cases of small cell carcinomas, which accounted for 2.8% of 180 surgically treated esophageal carcinomas, were reviewed for pathological findings, treatment, and outcome. Among three patients who had a small cell carcinoma of the esophagus with invasion limited to the submucosal layer, two patients survived for 7 and 9 years after surgery with no evidence of the disease. One of them was treated using surgery alone. Consequently, surgery may be considered as a possible choice of treatment for small cell carcinoma of the esophagus with invasion limited to the submucosa. PMID- 11206647 TI - Gastropericardial fistula after failure of laparoscopic hiatal repair. AB - We describe a 77-year-old patient with gastropericardial fistula occurring 5 years after laparoscopic surgery for hiatal hernia and gastroesophageal reflux. The patient presented with isolated intermittent substernal pain without fever. Chest radiographs disclosed extensive pneumopericardium and thoracic computed tomography suggested gastropericardial fistula between the pericardium and the surgical wrap, slipped into the thorax. Emergency surgery allowed successful repair through laparotomy via the trans-hiatal approach. PMID- 11206649 TI - AIDS and cultural practices in Africa: the case of the Tonga (Zambia). AB - The fight against AIDS in Africa is often presented as a fight against "cultural barriers" that are seen as promoting the spread of the HIV virus. This attitude is based on a long history of Western prejudices about sexuality in Africa, which focus on its exotic aspects only (polygamy, adultery, wife-exchange, circumcision, dry sex, levirate, sexual pollution, sexual cleansing, various beliefs and taboos, etc.). The article argues that those cultural aspects are a wrong target of AIDS prevention programs because they are not incompatible with a safer behavior, and because their eradication would not ensure the protection of people. To fight against them might alienate the people whose cooperation is necessary if one wants to prevent the spread of AIDS. The major problems of AIDS prevention in Africa are not specifically African, but are similar to the problems existing in Europe or America. Therefore, anti-AIDS projects should not fight against one local African culture in order to impose another (Western), but should rather try to make behavior and practises safer in a way that is culturally acceptable to people. PMID- 11206648 TI - Mental health and stress in the workplace: the case of general practice in the UK. AB - This study adopted a 'workforce' perspective in a study of job strain in primary care (general practice) in the UK. It explored the level of stress amongst workers in general practice and between practices and examined the relationship between level of stress and work characteristics. Postal questionnaires were sent to a random sample of general practices (n = 81) in southern England. The study showed that 23% of all responders could be classified, according to the GHQ-12, as suffering from mental distress with practice managers having the highest level of stress and clerical and administrative staff the lowest. Work characteristics as measured by Karasek's Job Content Instrument were shown to be significant predictors of job stress as were marital status and health status. The implications of these findings are discussed, particularly focusing on the value of the job strain model for explaining job stress in general practice. PMID- 11206650 TI - Understanding the dynamics of illness and help-seeking: event-structure analysis and a Cambodian-American narrative of "spirit invasion". AB - Event structure analysis (ESA) and its computer analog, ETHNO, represent a class of relatively new methodological approaches that make it possible to capture the complexity of help-seeking interactions. Using narrative data from a study of Cambodian-American help-seeking interactions within a circumscribed illness episode, this paper demonstrates the feasibility of using ESA/ETHNO to illuminate how event sequence, operant illness beliefs, structural conditions, and human agency interpenetrate and shape the occurrence and timing of pivotal actions and the denouement of a help-seeking episode. PMID- 11206651 TI - Gender trends in occupancy rates in mental health beds in Northern Ireland. AB - Based on census material from 1926 to 1991, this study focuses on gender differences in occupancy rates in mental health beds in Northern Ireland. More specifically, using two sets of research literature--the relationships between war and mental health and gender and mental health respectively--it explores changing patterns in bed occupancy in terms of both gender and age differences within this society. The results suggest that, although men and women no longer vary in terms of their overall occupancy rates within mental health facilities in Northern Ireland, within their respective male and female sub-populations, however, some notable age-specific differences have now emerged. Since 1981, whereas increases in mental health bed occupancy among women have been exclusively confined to the old (65 years or older), among males, it is the very young, specifically men aged 15-24 years, who have demonstrated the most dramatic rise in bed usage. It is important to note, however, that these age-specific gender increases cannot be accounted for by demographic changes in the general population. The authors suggest that, at least as far as men are concerned, the increasing pattern of vulnerability among the young may be attributed to the impact of changing definitions of mental disorder rather than to the effect of political violence on mental health. It is to this group of individuals--the cohort of men born since the outbreak of civil unrest in Northern Ireland in 1969 -that future research should be directed. PMID- 11206652 TI - Gender and health: reassessing patterns and explanations. AB - Recent research on gender and health challenges the prevailing notion of women's generalized health disadvantage by revealing a more variable pattern of gender differences in health. As such differences come to be comprehended as more complex than previously thought, there is a need to reassess the pathways linking gender and health. Using data from a Canadian national probability sample, we examine: (1) gender differences in distress, self-rated health, chronic conditions, restricted activity and heavy drinking; and (2) the role of gender based differential exposure and vulnerability to chronic stress and life events in explaining observed differences. We find that women report more distress and chronic conditions than men, but gender differences are reversed for heavy drinking, and negligible for self-rated health and restricted activity. Although women reported more chronic stress and life events, their greater exposure accounted for only some of the gender disparity in health, and only for distress. Differential vulnerability to stressors played no role in explaining gender differences in health. These findings raise questions about a gendered, generalized health response to the vicissitudes of life and suggest the need for further theoretical and empirical exploration of "gendered" experiences and their pathways to health. PMID- 11206653 TI - Knowledge, action and resistance: the selective use of pre-natal screening among Bedouin women of the Negev, Israel. AB - The selective use of prenatal screening by Bedouin women attending Ministry of Health, maternal and child health clinics in Israel is examined. The data consist of a review of 537 prenatal care records, 16 in depth interviews with mothers, and four interviews with health personnel. These data are part of a larger study that took place between 1994-99 amongst Negev Bedouin women, part of the Palestinian Arab minority within Israel. The record review shows that the majority of women who attend prenatal care do not take up referrals for Maternal Serum Alpha Feto Protein (MSAFP) testing or for amniocentesis tests. Although many women interviewed talked about the value of prenatal screening, they also spoke of 'false alarms' that may result from testing. Similarly, women were aware that the socially preferred pattern of consanguinity in marriage amongst the Bedouin may cause medical problems, however test uptake was unrelated to consanguinity. There was a variety of views concerning the permissibility of terminating a pregnancy. This study shows that women use prenatal screening selectively in a way that helps them to balance social and medical risk. PMID- 11206654 TI - Substance use during pregnancy in the state of California, USA. AB - Most analyses of prenatal substance use focus on individual level correlates and ignore community level variables and the effect of the dependency of respondents within communities. This analysis uses multilevel logistic regression models to more accurately assess the correlates of perinatal substance use in California. Statistical results indicate that a significant portion of substance use can be attributed to neighborhood heterogeneity, and that traditional models of substance use may inaccurately attribute this variation to individual level regression coefficients. Substantive results indicate that levels of neighborhood public assistance had an independent, significant effect on the prevalence of all substances tested for except alcohol. Black women had higher predicted prevalence risks for alcohol and cocaine while White women had higher predicted risks for tobacco, marijuana and amphetamines. Racial contrasts were non-significant for the overall illicit drug category and opiates, after controlling for neighborhood public assistance. Finally, individual level variables, with the exception of age, were not moderated by levels of neighborhood public assistance. PMID- 11206655 TI - Female control of sexuality: illusion or reality? Use of vaginal products in south west Uganda. AB - This paper reports on a trial of vaginal products that were distributed and used by 131 women and 21 men in south west Uganda. It focuses specifically upon the issue of female control in heterosexual relationships and examines whether methods which are ostensibly under women's control, will in practice give women greater control of their sexual health. Participants were invited to select two from a range of vaginal products that included the female condom, contraceptive sponge, film, tablets, foam and gel, and use each for five weeks and their favourite product for a further three months. They were interviewed up to seven times over a five-month period. Although the women perceived that a major advantage of the products (with the exception of the female condom) was that they could be used secretly, less than 40% were using the products without their partner's knowledge after one week and this proportion declined over time with only 22% using the products secretly after ten weeks. In the main male partners were told as women felt it their duty to inform them. In general the women were very much more positive about the products than they were about the male condom, as were the men. A contributory factor to their popularity among women was the greater control they gave them. Even though, use of these products in practice often involved negotiation with male partners, the fact that use was contingent on women's action was empowering and increased somewhat their ability to control their sexual health. PMID- 11206656 TI - High-risk behaviors and the prevalence of sexually transmitted diseases among women prisoners at the women state penitentiary in Metro Manila. AB - Women prisoners in the Philippines are particularly vulnerable to HIV infection. The economic and social disadvantages that women endure in mainstream society are magnified once they are committed to penitentiaries where control over one's own life is even more restricted and limited. Outside prison, impoverished and uninformed about the ways of protecting their health, women have engaged in unprotected sex with their male partners, many of whom have had casual sex or extra-marital affairs. Within prison, it is therefore not surprising that over 25% of women were already infected with sexually transmitted diseases (STDs). None were infected with HIV. The presence of STDs among female inmates highlights the importance of addressing health needs while at the correctional facility. It also raises the need for educational and prevention programs and health services that will help reduce women's vulnerability to HIV, AIDS and STDs. PMID- 11206657 TI - Predictors of patient satisfaction. AB - Correlates of patient satisfaction at varying points in time were assessed using a survey with 2-week and 3-month follow-up in a general medicine walk-in clinic, in USA. Five hundred adults presenting with a physical symptom, seen by one of 38 participating clinicians were surveyed and the following measurements were taken into account: patient symptom characteristics, symptom-related expectations, functional status (Medical Outcomes Study Short-Form Health Survey [SF-6]), mental disorders (PRIME-MD), symptom resolution, unmet expectations, satisfaction (RAND 9-item survey), visit costs and health utilization. Physician perception of difficulty (Difficult Doctor Patient Relationship Questionnaire), and Physician Belief Scale. Immediately after the visit, 260 (52%) patients were fully satisfied with their care, increasing to 59% at 2 weeks and 63% by 3 months. Patients older than 65 and those with better functional status were more likely to be satisfied. At all time points, the presence of unmet expectations markedly decreased satisfaction: immediately post-visit (OR: 0.14, 95% CI: 0.07-0.30), 2 week (OR: 0.07, 95% CI: 0.04-0.13) and 3-month (OR: 0.05, 95% CI: 0.03-0.09). Other independent variables predicting immediate after visit satisfaction included receiving an explanation of the likely cause as well as expected duration of the presenting symptom. At 2 weeks and 3 months, experiencing symptomatic improvement increased satisfaction while additional visits (actual or anticipated) for the same symptom decreased satisfaction. A lack of unmet expectations was a powerful predictor of satisfaction at all time-points. Immediately post-visit, other predictors of satisfaction reflected aspects of patient doctor communication (receiving an explanation of the symptom cause, likely duration, lack of unmet expectations), while 2-week and 3-month satisfaction reflected aspects of symptom outcome (symptom resolution, need for repeat visits, functional status). Patient satisfaction surveys need to carefully consider the sampling time frame as well as adjust for pertinent patient characteristics. PMID- 11206658 TI - Why do women use dietary supplements? The use of the theory of planned behaviour to explore beliefs about their use. AB - Dietary supplements use is increasing, despite the lack of evidence to suggest they are needed to meet dietary deficiency in the majority of people. Reasons for consuming dietary supplements are likely to be complex, combining social, psychological, knowledge and economic factors. The Theory of Planned Behaviour (TPB) is a widely used model of social cognition, which has recently been applied to the nutrition field. It was used in a questionnaire, along with a number of additional measures, to explore dietary supplement use in a cohort of women. Data from 303 questionnaires were included in the analysis. The results showed that intentions were the major predictor of dietary supplement use. Health value and susceptibility to illness were also significant predictors of dietary supplement use (total of 82.9% of respondents correctly classified as users or non-users). Intentions themselves were most strongly predicted by attitude, with 70% of variance explained by attitude, subjective norms and perceived behavioural control. Other significant predictors of intentions were control beliefs, normative beliefs and health value. Beliefs underlying dietary supplement use revealed differences between supplement users and non-users in relation to the notion that taking dietary supplements acts as an insurance against possible ill health, with supplement users believing more strongly than non-users that taking dietary supplements would stop them getting ill and help them to be healthy. Both users and non-users of supplements also perceived the media, in the form of books and magazines, to be a powerful influence on a person's decision to use supplements. The findings of this study highlight the potential of the TPB in exploring supplement-taking behaviour, while throwing light on the factors influencing an individual's motivations to use dietary supplements. PMID- 11206659 TI - Managing and treating risk and uncertainty for health: a case study of diabetes among First Nation's people in Ontario, Canada. AB - 'Risk' has become a key concept for understanding health care policies that are focused on prevention. Intervention no longer depends on the presence of an illness but rather an individual's risk of developing an illness. Through 'risk factors' individuals are subject to medical examination and surveillance to determine the real presence of danger, based on this abstract notion of risk. This paper explores 'risk' and its consequences for medical intervention by focusing on biomedical practices surrounding diabetes care among First Nations on Manitoulin Island, Ontario. The first section explores the process of diagnosing diabetes. The second section outlines the treatment regimens resulting from membership in this category. The theme linking these two processes is that both diagnosis and management of diabetes depend on inclusion into categories of 'risk'. Practices surrounding diagnosis focus on a population described 'at risk' for diabetes. First Nation's people. Similarly, practices surrounding management of diabetes focus on a population 'at risk' for secondary complications, referring to individuals with diabetes. As the following discussion outlines, it is through the quantitative assessment of risk that scientific uncertainty is translated into definitive therapy and the need for constant surveillance. PMID- 11206660 TI - The impact of health status on work, symptoms, and functional outcomes in severe mental illness. AB - This study evaluated the relationships between self-ratings of physical role functioning and general health, two components of the MOS SF-36, and a variety of demographic, quality of life, clinical, functional, and attitudinal variables in a cohort of adults living with severe and persistent mental illness (SPMI). We hypothesized that poorer self-perceptions of physical functioning and general health would be significantly related to more severe symptoms and poorer functioning and quality of life. Study subjects were 218 adults with SPMI enrolled in a randomized controlled trial comparing two vocational interventions for persons who were unemployed. Hierarchical regression analysis was used to determine whether psychiatric symptoms, poorer self-perceptions of role limitations due to physical health problems and overall general health independently contributed to more severe symptoms and poorer functioning and quality of life. Psychiatric symptoms were inversely related to size of social network and satisfaction with safety. Increased role limitations were associated with reduced medication compliance, general life satisfaction, and satisfaction with health, daily activities, and safety. Reduced general health was significantly associated with reduced work motivation, self-esteem, current inability to work, self-report of functioning, and almost all subjective life satisfaction domains. Within this group of people with severe mental illness, psychiatric symptoms were minimally associated with outcomes. Physical role limitations contributed more, and an integrated global measure of overall health perception was most important. If we are to help persons with severe mental illness maximize their quality of life and functioning, our clinical interventions should employ an approach that appreciates and recognizes the importance of the patients' experience of a holistic and integrated experience of health. PMID- 11206661 TI - Insight changes in acute psychotic episodes: a prospective study of Hong Kong Chinese patients. AB - Insight impairment occurs commonly in psychotic disorders (including mood episodes with psychotic symptoms). The aim of the present study is to measure changes of insight over the course of a psychotic episode and to investigate its relationships with symptoms and neurocognitive functions, as well as psychosocial factors. Insight was assessed at weekly intervals in 80 consecutive inpatients presenting with a psychotic episode by using a Chinese translation of the Scale to Assess Unawareness of Mental Disorder (SUMD). The relationships between insight change and other variables were explored. Modest but significant changes in insight were found in both directions with clinical resolution of psychotic symptoms. In particular, insight "declined" as symptoms improved in a number of patients. In addition, changes in insight score correlated with changes in Wisconsin Card Sorting Test (WCST) performance. More changes in insight (in either direction) tended to occur in younger patients. These results indicated that adequate control of psychotic symptoms and improvement in neuropsychological functioning might be associated with better insight recovery. PMID- 11206662 TI - Impact of family burden and patient symptom status on clinical outcome in bipolar affective disorder. AB - Studies have suggested that family burden adversely affects clinical outcome in the major mental disorders. Logistic regression analysis was used to evaluate the effect of family burden reported at baseline (acute model), or 7 months (stabilization model), on the risk of having a subsequent affective episode, in a sample of 264 patients with Research Diagnostic Criteria-diagnosed bipolar illness. Higher levels of baseline burden and a depressive index episode significantly increased the risk for a major episode at 7 months. Higher 7-month burden significantly increased the risk for a major episode at 15 months among patients with relatively low 7-month BPRS symptom levels. Caregiver burden reported at times of symptom relapse and during stabilization predicts subsequent adverse clinical outcomes among patients with bipolar disorder and suggests a need for family support. PMID- 11206664 TI - Effects of exposure to death in a war mortuary on posttraumatic stress disorder symptoms of intrusion and avoidance. AB - Exposure to the dead has been an important subject for traumatic stress research, considering that such exposure is a risk factor for posttraumatic stress disorder (PTSD). Individuals required to handle the dead from war are exposed to multiple stressors. No previous studies, however, have examined pre- and post-responses to traumatic death. We studied the pre-post responses of 352 military men and women who worked in the mortuary that received the dead from the Persian Gulf War (Operation Desert Storm) in 1990 to 1991. The respondents were volunteers and nonvolunteers for assignment to the mortuary; some had prior experience in handling the dead and some did not. Symptoms of intrusion and avoidance were measured before and after exposure. Four groups were examined based on the degree of exposure to remains. Age, sex, volunteer status, and prior experience handling remains were statistically controlled. Post-exposure intrusion symptoms increased significantly for all groups exposed to the dead. Increased post-exposure avoidance symptoms were present in the two groups with the greatest exposure to remains. There were no significant increases in intrusion or avoidance in the unexposed group. PMID- 11206663 TI - Family functioning in subjects with pseudoseizures and epilepsy. AB - The purpose of this study was to identify differences in family functioning between subjects with pseudoseizures and their families, and control subjects with epilepsy. Thirty-one adult subjects with pseudoseizures and 31 controls with intractable epilepsy, whose diagnoses were confirmed using video-EEG, were recruited from the epilepsy unit of a tertiary care hospital over a 4-year period. Each study participant and their first-degree adult family members completed two standardized questionnaires designed to measure family functioning: the McMaster Family Assessment Device (FAD) and the Beavers Self-Report Family Inventory (SFI). Individuals with pseudoseizures, when compared with epileptic subjects, exhibited significantly elevated scores in three scales of the FAD and in one scale of the SFI, indicating greater psychopathology within the family, as perceived by the individual. Statistically significant differences with the FAD were on measures of affective involvement (p = .044), communication (p = .004), and general functioning (p = .013). The SFI revealed significantly greater difficulty with conflict (p = .050). No differences were noted between subjects with both pseudoseizures and epilepsy and subjects with pseudoseizures alone. In comparison with the families of the epileptic group, the families of subjects with pseudoseizures displayed statistically significant elevations in their responses on the roles scale (p = .003) of the FAD. The responses of the family members did not differ in regard to the role they assumed within the family unit (i.e., spouse, parent). In summary, individuals with pseudoseizures view their families as being more dysfunctional, particularly in the area of communication, whereas their family members perceived difficulties in defining roles. This suggests that family education and interventions focusing on these areas, may be an important aspect of the treatment of patients with pseudoseizures. PMID- 11206665 TI - Characteristics of people lost to attrition in psychiatric follow-up studies. AB - In a large (N = 1,744) study of previously hospitalized psychiatric patients, multiple follow-up attempts were made to contact the ex-patients over a 1-year period after their discharges. When contacted they were asked to provide information about their posthospital adjustment; 59.5% of the sample was reached at least once and usable data obtained either in a telephone interview or from a mailed survey form. The contacted and noncontacted people represented very different subpopulations, both demographically and in terms of typical psychiatric descriptors. Those who were of lower socioeconomic status, male, unmarried, racial minorities, and those with records of substance abuse or assaultiveness, and who were generally more severely impaired during the baseline hospitalization were underrepresented in the contacted group. Possible reasons for these sample biases, the implications for hospitals conducting outcome assessments (i.e., for research and program evaluation purposes), and strategies for dealing with this kind of methodological problem are discussed. PMID- 11206666 TI - Literacy in the psychiatric emergency service. PMID- 11206667 TI - Mixed handedness and trauma symptoms in disaster-exposed adolescents. PMID- 11206668 TI - Evaluating the tolerability of the newer mood stabilizers. PMID- 11206669 TI - Benefit of long-term stimulants on driving in adults with ADHD. PMID- 11206670 TI - The association between antisaccade task and working memory task performance in schizophrenia and bipolar disorder. AB - To date, the research literature has yielded conflicting reports regarding the specificity of antisaccade deficits to schizophrenia. We sought to examine antisaccade and working memory task performance in schizophrenia patients and bipolar patients, as well as to examine the relationship between the two tasks in both patient populations. Thirty-four schizophrenia patients, 20 bipolar patients, and 30 nonpatient controls were administered saccadic inhibition (antisaccade), working memory, and sensorimotor tasks. Compared with the controls, the schizophrenia patients displayed both antisaccade deficits and working memory deficits. In contrast, the bipolar patients produced significantly more errors on the antisaccade task than the controls, though the bipolar group performed similarly to the control group on the working memory task. Mediational analyses demonstrated that working memory partially mediates the relationship between patients' diagnostic group status and antisaccade task performance; working memory performance contributed uniquely to the prediction of antisaccade task performance in the two patient groups. Antisaccade deficits do not appear specific to schizophrenia. The results suggest that in schizophrenia, working memory and antisaccade tasks are tapping similar cognitive processes, whereas in bipolar patients the processes underlying antisaccade and working memory performance are disparate. PMID- 11206671 TI - A glance back: one year into the millennium. PMID- 11206672 TI - A new chronotherapeutic oral drug absorption system for verapamil optimizes blood pressure control in the morning. AB - A novel verapamil chronotherapeutic oral drug absorption system (CODAS-Verapamil) designed for bedtime dosing and with controlled onset and extended-release properties was evaluated in 257 patients with mild-to-moderate essential hypertension in an 8-week, double-blind, placebo-controlled trial. After bedtime dosing (9 PM to 11 PM, this delivery system delays drug release for 4 to 5 h, and provides the highest concentrations of verapamil between 6 AM and noon. The study results showed that CODAS-verapamil produced its greatest antihypertensive effect during this morning period (6 AM to 12 noon) and also provided effective trough diastolic blood pressure reductions at 200, 300, and 400 mg. Significant trough systolic blood pressure reductions were achieved only with the 300- and 400-mg doses. The nighttime dosing regimen was not associated with excessive blood pressure (BP) reductions during the sleeping hours, when the antihypertensive effect was generally slightly less than that of the 24-h mean reduction. The CODAS-verapamil provides enhanced BP reduction during the morning period when compared with other time intervals of the 24-h dosing period. PMID- 11206673 TI - Inverse association of Chlamydia pneumoniae infection with high blood pressure in Japanese adults. AB - To determine whether Chlamydia pneumoniae (C. pneumoniae) infection is associated with hypertension in Japanese adults, we measured serum levels of IgA (a marker of reinfection) and of IgG (a marker of previous infection) antibodies to C. pneumoniae by enzyme-linked immunosorbent assay in 112 adults including normotensive and untreated hypertensive subjects and in 117 hypertensive subjects who had been receiving treatment for more than 3 years. In 112 adults, positivity rate for IgA was lower (P < .01) in hypertensive than in normotensive or borderline hypertensive subjects. Positivity rates for IgA and IgG together, which indicate persistent infection of C. pneumoniae, were lower (P < .01) in hypertensive than in normotensive subjects. IgA levels were inversely correlated with systolic blood pressure (SBP) (r = 0.530, P = .0001) and with diastolic blood pressure (DBP) (r = 0.398, P = .0001). In the 117 hypertensive subjects treated with medication, positivity rate for IgA was lower (P < .01) in subjects with poor control than in those with good control. Positivity rates for IgA and IgG together were lower (P < 0.01) in the poor control group than in the good or fair control groups. IgA levels were correlated inversely with SBP and DBP. In both 112 adults and 117 hypertensive patients, levels of SBP or DBP were inversely associated with positivity rates for IgA and IgG together in multiple logistic regression analysis. The results suggest an inverse relationship between high blood pressure and C. pneumoniae infection in Japanese adults. PMID- 11206675 TI - Nitric oxide does not participate in the metabolic effects of exogenous bradykinin in fructose-fed rats. AB - The study was carried out to demonstrate the effects of bradykinin (BK) on hypertension, hyperinsulinemia, and hypertriglyceridemia in fructose-fed rats, and to determine whether these actions are mediated through nitric-oxide (NO) formation. Eighteen rats, rendered hypertensive, hyperinsulinemic, and hypertriglyceridemic by a fructose-enriched diet, were studied. BK (0.2 mg/day) was infused intravenously using osmotic pumps attached by a catheter to the jugular vein of 12 rats for 12 days. BK was administered either alone (n = 6) or with concomitant inhibition of NO synthase (n = 6). Six untreated rats served as control. Measurements of systolic blood pressure (indirect method) and levels of insulin and triglyceride in serum were taken every second day. BK infused chronically, induced a marked fall in all parameters as early as the second day of infusion: in blood pressure from 152+/-7 to 126+/-12 mmHg, in insulin from 8.7+/-2.9 to 4.6+/-5.4 pg/mL, and in triglyceride from 308+/-94 to 76+/-19 mg/dL. No such reduction was seen in untreated animals. When BK was administered concurrently with NO synthase inhibitor, blood pressure rose significantly, reaching very high values at the end of treatment. However, the reduction in insulin and triglyceride levels induced by BK was not affected. The capacity of BK to enhance reduction in hyperinsulinemia and hypertriglyceridemia in the fructose-fed rats is not mediated by NO formation. Whether this action of BK is related to a direct effect of this peptide remains to be determined. PMID- 11206674 TI - Sexual activity in hypertensive men treated with valsartan or carvedilol: a crossover study. AB - The aim of this study was to compare the effect of antihypertensive treatment with valsartan or cavedilol on sexual activity in hypertensive men who were never treated for hypertension. A total of 160 newly diagnosed hypertensive men (diastolic blood pressure [DBP] > or = 95 mm Hg and < 110 mm Hg), aged 40 to 49 years, all married and without any previous sexual disfunction, were enrolled. After a 4-week placebo period, the patients were divided into two groups: a) 120 patients were randomized to receive carvedilol 50 mg once daily or valsartan 80 mg once daily for 16 weeks according to a double-blind, cross-over design; after another 4-week placebo period, patients were crossed over to the alternative regimen for a further 16 weeks; b) 40 patients were treated with placebo according to a single-blind design for 16 weeks. At the screening visit and every 4 weeks thereafter, blood pressure (BP) was evaluated and patients were interviewed by a questionnaire about their sexual activity. Blood pressure was significantly lowered by both treatments, with a 48% of normalization with valsartan and 45% with carvedilol. During the first month of therapy, sexual activity (assessed as number of sexual intercourse episodes per month) declined with both drugs as compared with baseline, although the decrease was statistically significant in the carvedilol (from 8.2 to 4.4 sexual intercourse episodes, P < .01) but not in the valsartan-treated patients (from 8.3 to 6.6 sexual intercourse episodes, not significant). Ongoing with the treatment the sexual activity further worsened with carvedilol (3.7 sexual intercourse episodes per month) while fully recovered and also improved with valsartan (10.2 sexual intercourse episodes per month). The results were confirmed by the cross-over. Erectile dysfunction was a complaint of 15 patients with carvedilol (13.5%), one patient with valsartan (0.9%), and one patient in the placebo group. These findings suggest that carvedilol induces a chronic worsening of sexual activity, whereas valsartan not only does not significantly worsen sexual activity but may even improve it. PMID- 11206676 TI - Relation between sodium-lithium countertransport and hypertriglyceridemia in type V hyperlipidemia. AB - Sodium-lithium countertransport (SLC) kinetics were measured in 30 patients with type V hyperlipidemia, 30 patients with type IIB hyperlipidemia on similar treatment, and 30 age- and sex-matched healthy controls. Clinical and laboratory data including basic anthropometry and blood pressure were obtained and blood was taken for detailed lipid biochemistry, glucose, insulin, and leptin measurements. Patients with type V hyperlipidemia were normotensive but more obese than controls, had elevated triglycerides, very low-density lipoprotein, glucose, and insulin; and reduced HDL cholesterol compared with type IIb controls. The median SLC activity (0.23 v 0.21 mmol Li+/L RBC/h) and median maximal velocity (0.33 v 0.31 mmol Li+/L RBC/h) were increased, but not significantly, compared to controls. In patients with type V hyperlipidemia SLC maximal velocity correlated with log triglycerides (r2 = 0.853; P < .001) and log very low-density lipoprotein (VLDL) triglycerides (r2 = 0.947; P < .001). Sodium-lithium countertransport maximal velocity correlated weakly with the homeostasis model assessment index of insulin resistance (r2 = 0.224; P = .06). The sodium affinity of the transporter did not differ between the groups and was independent of any of clinical or biochemical parameter studied. We conclude that VLDL triglyceride is strongly correlated with SLC maximal velocity and activity in patients with type V hyperlipidemia. PMID- 11206677 TI - Sleep effects on ambulatory blood pressure measurements in pregnant women. AB - The aim of this study was to investigate the effect of the definition of daytime and nighttime on ambulatory blood pressure (ABP) in pregnancy. To determine the prevalence of a <10% decrease in mean arterial pressure with sleep (nondipper) in pregnancy and the consistency of nondipper status throughout pregnancy. In a prospective, longitudinal study, 102 pregnant woman underwent 24-h ABP monitoring and recorded sleep patterns at < or = 14, 19 to 22, 27 to 30, 35 to 37 weeks' gestation and 5 to 9 weeks' postpartum. Nighttime was defined by arbitrary hours or actual periods of sleep. Ambulatory blood pressure measurements using the different definitions of nighttime were compared in the total cohort and individual women. Nondipper status of each woman was determined throughout pregnancy and postpartum. At 35 to 37 weeks' gestation, 19% of women napped during the day and 20% were awake during the night. Throughout pregnancy, mean day and night systolic and diastolic ABP measurements were similar whether daytime and nighttime were defined by arbitrary hours or by sleep periods. In individuals, the use of arbitrary hours (day 07:00 to 21:59, night 22:00 to 06:59) compared to sleep periods to define day and night resulted in differences in daytime systolic (SBP) and diastolic blood pressure (DBP) of up to 4 and 5 mm Hg, respectively. Similarly there were individual differences in nighttime SBP up to 10 mm Hg and DBP up to 11 mm Hg. A third of women were nondippers at least once during pregnancy, but only two women were consistent nondippers. The different definitions of day and night did not change group ABP measurements, but resulted in significant variation in ABP measurements in individual pregnant women. Nondippers were common and nondipper status frequently changed during pregnancy. PMID- 11206678 TI - Endogenous ouabain and hemodynamic and left ventricular geometric patterns in essential hypertension. AB - We sought to evaluate the relationships among circulating levels of an endogenous ouabain-like factor (EO) and systemic hemodynamics and left ventricular (LV) geometry in patients with recently diagnosed essential hypertension. We selected 92 never-treated patients with essential hypertension. Blood samples were drawn for estimation of plasma EO (radioimmunoassay) and subjects underwent echocardiographic examination to evaluate LV end-systolic and end-diastolic wall thickness and internal dimensions. LV volumes, stroke volume, cardiac output, total peripheral resistance, LV mass, and relative wall thickness were calculated, and all except the last parameter were indexed by body surface area. LV mass also was indexed by height. On the basis of the values of LV mass index (body surface area or height) and relative wall thickness, subjects were divided into groups with either normal geometry, concentric remodeling, concentric hypertrophy, or eccentric nondilated hypertrophy. In the study population as a whole, circulating EO levels were significantly and directly correlated with mean blood pressure (r = 0.21, P = .048), relative wall thickness (r = 0.34, P = .001), and total peripheral resistance index (r = 0.37, P = .0003). Plasma EO also was significantly and inversely correlated with LV end-diastolic volume index (r = -0.32, P = .002), stroke index (r = -0.34, P = .0009), and cardiac index (r = -0.35, P = .0007). In multiple regression analysis, plasma EO was an independent correlate of total peripheral resistance index, cardiac index, and relative wall thickness. Regardless of the indexation method used for LV mass, plasma EO was higher in patients with concentric remodeling than in those with either normal geometry or concentric hypertrophy. Plasma EO tended to be higher (indexation by body surface area) or was significantly higher (indexation by height) in subjects with concentric remodeling than in those with eccentric nondilated hypertrophy. Patients with concentric remodeling showed the highest total peripheral resistance index and the lowest cardiac index. Our data suggest that EO plays a role in regulating systemic hemodynamics and LV geometry in patients with essential hypertension. PMID- 11206679 TI - Correlation between the glucose clamp technique and the homeostasis model assessment in hypertension. AB - The homeostasis model assessment (HOMA) has been extensively used as a reliable surrogate marker for measuring insulin resistance in patients with diabetes mellitus and in normal subjects. Comparative data in another insulin resistance state, hypertension, is lacking. The goal of the present study was to obtain that information by testing the correlation of HOMA with the euglycemic hyperinsulinemic clamp in 36 hypertensive and 27 normotensive subjects. Clamp derived insulin sensitivity was calculated as the glucose disposal rate over steady-state plasma insulin concentration. Homeostasis model assessment was computed using the formula (fasting glucose x fasting insulin)/22.5. There was significant correlation between the clamp and HOMA for both the hypertensive (r = -0.64, P < .0001) and normotensive subjects (r = -0.58, P = .002). The HOMA can be used reliably as a less expensive and less cumbersome alternative for measuring insulin resistance in hypertension. PMID- 11206680 TI - Losartan versus enalapril on cerebral edema and proteinuria in stroke-prone hypertensive rats. AB - Stroke-prone spontaneously hypertensive rats (SHRSP), subjected to high NaCl, show severe hypertension, organ damage, and early death. Preventive treatment with angiotensin II type 1 (AT1) receptor antagonists is known to be effective. Previously, we found that angiotensin converting enzyme (ACE) inhibition could reduce cerebral edema when treatment was started after manifestation of either proteinuria or cerebral edema. In this study AT1 receptor blockade was started at the same time points to evaluate whether this had an effect superior to ACE inhibition. SHRSP drank 1% NaCl. Group 1 served as controls. Group 2 and 3 rats were started on losartan and enalapril after proteinuria exceeded 40 mg/day. Group 4 and 5 rats were started on losartan and enalapril after the first observation of cerebral edema with T2-weighted magnetic resonance imaging scans. In controls, median survival was 54 days (range, 35 to 80 days) after the start of salt loading. With early-onset losartan and enalapril, survival increased to 305 days (range, 184 to 422 days) and 320 days (range, 134 to 368 days) (both P < .01 v group 1). Cerebral edema formation was prevented in all but two rats, one from each treatment modality. Development of proteinuria was markedly reduced. With late-onset treatment with losartan and enalapril, survival was 290 days (range, 120 to 367 days) and 264 days (range, 154 to 319 days) (both P < .01). Both losartan and enalapril decreased cerebral edema to baseline levels. Ultimately cerebral edema reoccurred, despite continued treatment, in 75% of the rats. Systolic blood pressure did not decrease after losartan treatment, but, similarly to early-onset treatment, decreased transiently after enalapril treatment. Cerebral edema and proteinuria were prevented and reduced in SHRSP treated with either an AT1 receptor antagonist or an ACE inhibitor. Survival was markedly and similarly prolonged by both treatments, whether initiated directly before or after development of cerebral edema. In rats where treatment was initiated after manifestation of cerebral edema, both cerebral edema and proteinuria reappeared despite continued treatment. Apparently, when hypertension is sustained, reappearance of target organ damage may not be entirely dependent on angiotensin. PMID- 11206681 TI - Hypertension due to renal artery occlusion in a patient with antiphospholipid syndrome. AB - We report an unusual case of renovascular hypertension in a 16-year-old boy with primary antiphospholipid syndrome (PAPS), admitted to our clinic for severe drug resistant hypertension and hypokalemia. Hormonal investigation revealed secondary aldosteronism and positive captopril test for renovascular disease. Aortography confirmed the occlusion of the left renal artery. After nephrectomy, normalization of blood pressure and secondary aldosteronism occurred. Presently the patient remains in good health, receiving warfarin anticoagulant therapy. PAPS is defined by the presence of antiphospholipid antibodies and recurrent thrombosis. Arterial thrombosis (29%) appears to be less prevalent than venous thrombosis. Thrombotic microangiopathy of the kidney is frequently observed but renal artery occlusion, as seen in our patient, is unusual. PMID- 11206682 TI - Effects of short- and long-acting calcium channel blockers on the relationship between blood pressure and physical activity. AB - Calcium channel blockers are widely used as antihypertensive drugs. However, there is some controversy as to how they should be used. Our first aim was to clarify how the dihydropyridine calcium channel blocker, benidipine, affects the quantitative relationship between blood pressure (BP) and physical activity. The second aim was to determine whether there is a relationship between systolic blood pressure (SBP) and physical activity in patients with hypertension when treating with a short-acting (nifedipine) or long-acting (benidipine) calcium channel blocker. In Study 1, ambulatory BP and physical activity were measured simultaneously in 27 patients with hypertension before and after 6 months with benidipine. In Study 2, ambulatory BP and physical activity were measured simultaneously in 16 patients with hypertension before (placebo) and after 6 weeks of crossover treatment with nifedipine and benidipine. In Study 1, there was no difference in the SBP change caused by physical activity between the pre- and posttreatment periods. In Study 2, SBP was significantly related to physical activity in the placebo (16/16) and benidipine (16/16) groups but not in the nifedipine (12/16) group. The lowest BP during day-time and nighttime in the nifedipine group were significantly lower than those in the benidipine group. Plasma renin activity (ng/mL/h) was significantly higher in the nifedipine group (1.20+/-1.05) than in the placebo (0.57+/-0.59) and benidipine (0.75+/-0.78) groups. These findings indicate that nifedipine might interfere with the adaptation mechanism of BP changed by physical activity and that the activated renin-angiotensin system might cause cardiac events. PMID- 11206683 TI - Coronary microvasculature alteration in hypertensive rats. Effect of treatment with a diuretic and an ACE inhibitor. AB - The development of hypertension is accompanied by rarefaction of arterioles and capillaries in both animal models and humans. Although many studies have examined the effects of antihypertensive therapies on hemodynamics, cardiac hypertrophy, and large vessel structure, the question of whether changes in microvascular density induced by hypertension can be restored by pharmacologic treatment has yet to be answered. We report a series of experiments performed in rats with renovascular hypertension induced by unilateral nephrectomy and renal artery stenosis (Goldblatt one-kidney, one-clip model). Animals were treated for 4 weeks, after renal artery clipping, either with an angiotensin converting enzyme inhibitor (perindopril [PER], 0.76 mg/kg/day), or with an indol derivative diuretic with specific vascular properties (indapamide [IDP], 0.24 mg/kg/day) or with the combination of both drugs at the same doses as during monotherapy. Coronary microvessel densities (arterioles and capillaries) were evaluated by double immunolabeling in nonserial cryostat sections of the left ventricular inner myocardium. After 4 weeks of hypertension (mean arterial pressure, 174+/-11 v 124+/-5 mm Hg in normotensive (NT) controls, P < .01), cardiac hypertrophy (+59%, P < .001) was associated with a significant increase in myocardial arteriolar density (+27%, P < .01), and a decrease in capillary density (-12%, P < .05). Treatment with PER prevented the increase in arterial pressure, heart weight, and arteriolar density, but did not significantly affect the low coronary capillary density in comparison with that measured in untreated hypertensive (HT) rats. Treatment with IDP preserved normal capillary myocardial density but did not significantly lower the blood pressure (BP) (169+/-9 mm Hg) and only slightly reduced the cardiac ventricular hypertrophy: - 14% v untreated HT (P < .05) and +37% v NT (P < .01). In the same way, IDP normalized the left ventricular capillary density in spontaneously HT rats (+18% v untreated rats, P < .01). The combination of both drugs, PER and IDP, at the same low doses as during monotherapy, resulted in normal levels of arterial pressure and complete normalization of cardiac hypertrophy and arteriolar and capillary myocardial densities. In conclusion, the results observed after PER suggest that blockade of the renin-angiotensin system could inhibit large coronary vessel growth but minimally affects the capillary density despite complete normalization of BP. Indapamide could have beneficial effect on myocardial capillary density. The combination of IDP and PER has additional effects and prevents the increase in BP and cardiac weight, and reverses microvascular rarefaction, specifically arteriolar and capillary densities. PMID- 11206684 TI - Effect of sildenafil in patients with erectile dysfunction taking antihypertensive therapy. Sildenafil Study Group. AB - Oral sildenafil is an effective treatment for erectile dysfunction (ED), which is a common complaint for patients with hypertension and those taking antihypertensive agents. This post hoc subanalysis assessed the efficacy and safety of sildenafil in men with ED who were receiving concomitant antihypertensive medication. Efficacy was assessed in 3414 men (1218 of whom were taking antihypertensive medication) who received sildenafil (5 to 200 mg) or placebo for 6 weeks to 6 months in 10 double-blind, placebo-controlled studies. The significant improvements in erectile function demonstrated by sildenafil treated patients were comparable in patients taking and those not taking antihypertensive medication. Safety was assessed in 3975 men (1094 of whom were taking one or more antihypertensive agent, classified as a diuretic, beta blocker, alpha1-blocker, angiotensin converting enzyme inhibitor, or calcium channel blocker), who received sildenafil or placebo in 18 double-blind, placebo controlled studies. For patients taking sildenafil and antihypertensive medication, the incidence of treatment-related adverse events (34%) was similar to that for sildenafil-treated patients not taking any antihypertensive agent (38%). The incidences of the most common adverse events and of adverse events potentially related to blood pressure decreases (eg, hypotension, dizziness, and syncope) were similar in both sildenafil groups. The number of antihypertensive medications taken from among the five classes had no effect on the adverse event profile of sildenafil. Sildenafil is an effective and well-tolerated treatment for ED in patients taking concomitant antihypertensive medication, including those on multidrug regimens. PMID- 11206685 TI - Device-guided breathing exercises reduce blood pressure: ambulatory and home measurements. AB - Slow breathing practiced routinely using an interactive device has demonstrated a sustained reduction in high blood pressure (BP). We reevaluated the BP response of hypertensives (n = 13) to this daily treatment for 8 weeks using 24-h ambulatory, home, and office BP measurements. A clinically significant BP reduction of similar magnitude was observed in all BP monitoring modalities during the daytime. Greater BP reductions were found for older patients and higher baseline BP. The results provide additional support for the efficacy of the device as an adjunctive lifestyle modification for treating hypertension. PMID- 11206686 TI - Preeclamptic serum enhances endothelin-converting enzyme expression in cultured endothelial cells. AB - Increased vascular sensitivity to vasoconstrictors, such as angiotensin II and epinephrine, is observed in preeclampsia (PE). Recently, it was suggested that abnormal endothelial function might contribute to the pathophysiologic changes in PE. We investigated vasoconstrictor (angiotensin II and epinephrine)-induced endothelin-1 (ET-1) release from human umbilical vein endothelial cells incubated with sera from women with PE compared with normotensive pregnant and nonpregnant women. Moreover, inositol 1,4,5-trisphosphate production and endothelin converting enzyme (ECE) expression in human umbilical vein endothelial cells were also evaluated. There were no significant differences in ET-1 release without vasoconstrictors among the three groups (nonpregnant, normotensive pregnant, and PE). No significant differences in basal inositol 1,4,5-trisphosphate production and ECE expression without vasoconstrictors were detected among the three groups. Vasoconstrictor-induced ET-1 release was significantly increased by PE sera. No significant difference was detected in vasoconstrictor-induced inositol 1,4,5 trisphosphate production among the three groups. However, ECE expression after incubation with vasoconstrictor was significantly increased by PE sera. Our results suggest that ET-1 release from endothelial cells may contribute to the increased vascular sensitivity to vasoconstrictors observed in PE, and that vasoconstrictor-induced ET-1 release may be related to enhanced ECE expression. PMID- 11206687 TI - Laragh's lessons in pathophysiology and clinical pearls for treating hypertension. PMID- 11206688 TI - Teenage women's use of contraceptives in two populations. AB - BACKGROUND: Adolescent patterns of contraceptive use might be different in various populations and might have changed in the last 30 years. More appropriate use of contraception could prevent unplanned pregnancy. METHODS: We interviewed 378 women in rural East Tennessee and 396 women in suburban-urban Baltimore, all of whom were aged 18 to 50 years, in a convenience sampling about their memories of sexual experiences and early contraceptive use. RESULTS: First sexual experiences began at a younger age in women from Tennessee than in women from Baltimore. Sexual experiences occurred at an earlier age during the last 15 years in Baltimore women. Contraceptive use at first sexual experience has approximately doubled in both locations, from 7% to 15% in Tennessee and from 42% to 75% in Baltimore during the last 15 years. The primary reason in Baltimore is increased use of condoms. Condom use in Tennessee is very low. CONCLUSIONS: These two populations are using contraception and condoms differently. Although the two populations are diverse, it could help physicians to learn about the particular contraceptive practices of their patient population to help their patients more appropriately with their contraceptive needs. PMID- 11206689 TI - Comparison of anticoagulation clinic patient outcomes with outcomes from traditional care in a family medicine clinic. AB - BACKGROUND: Giving patients oral anticoagulation therapy in an ambulatory clinic setting is associated with substantial risk of adverse outcomes leading to emergency department visits and unplanned inpatient admissions. This article describes an effectiveness study conducted in a well-characterized family practice setting that compares anticoagulation outcomes in patients managed by a traditional care model with outcomes obtained with an anticoagulation clinic model. METHODS: All study patients received continuous anticoagulation care at the Family Medicine of Southwest Washington (FMSW) clinic during the 1-year study period. The method was retrospective and used linked record review, including outpatient, inpatient, and emergency department records. Patients were divided into two groups as naturally observed: those treated in the clinic by traditional care compared with those treated in an anticoagulation clinic model. Data analyses compared the two groups in terms of patient demographics, anticoagulation control, and inpatient admissions and emergency department visits that were related to clotting or bleeding events. RESULTS: There were no differences in demographic variables between the anticoagulation clinic and traditional care groups. There was a statistically significant difference in anticoagulation control as measured by international normalized ratio (INR) values. The anticoagulation clinic group had fewer INR values outside the target range, +/- 0.1, than the traditional care group (40.4% vs 47.3% P = .022). The anticoagulation clinic group also had significantly fewer INR tests drawn more than 6 weeks apart than the traditional care group (3.7% vs 8.1% P = .01). There was no statistically significant difference in emergency department visit rates caused by adverse events. Inpatient admission rates for the anticoagulation clinic and traditional care groups were not statistically different; however, they were clinically different (4.7 vs 19.7 admissions per 100 patient years of therapy P = .15). CONCLUSIONS: More anticoagulation patients treated by the anticoagulation clinic model at FMSW received an INR test at least every 6 weeks than those treated by the traditional care model, and more of their INR results were within target range +/- 0.1 when compared with the traditional care model. PMID- 11206690 TI - Compounded percutaneous testosterone gel: use and effects in hypogonadal men. AB - BACKGROUND: Current methods of testosterone replacement therapy are limited to fixed-dosage patches and depot injections. Neither of these methods provides ideal therapy because of the inflexibility of dosing and other nuisance problems associated with the patches and nonphysiologic hormone levels when depot injections are used. Testosterone gels offer the potential for convenience and ease of administration, as well as flexible dosing regimens, by means of a simple topical application. METHODS: Ten hypogonadal men were selected from the author's general practice, ranging in age from 44 to 77 years. Four of these men had newly diagnosed and 6 had preexisting hypogonadism. Patients were withdrawn from their previous hormone therapy (where applicable), and baseline laboratory studies were obtained for total testosterone, free testosterone, dihydrotestosterone, estradiol, luteinizing hormone, follicle-stimulating hormone, complete blood counts, lipid panels, and chemistry panels. The patients then started taking increasing dosages of the testosterone gel until physiologic levels of testosterone were realized or until the study period (6 weeks) was concluded. There was no blinding, and each patient served as his own control. Testosterone and free testosterone levels were monitored weekly, and estradiol and dihydrotestosterone less frequently. At the conclusion of the study, all the baseline laboratory tests were repeated. A questionnaire evaluating the psychosexual well-being of the patients was administered before and after the treatment period. RESULTS: The average total testosterone level rose from 136 ng/dL to 442.9 ng/dL (P < .001). Average free testosterone levels rose from 34.2 pg/mL to 120.3 pg/mL (P < .001). Average dihydrotestosterone levels rose from 20.5 to 199.2 ng/dL (P = .006). Average estradiol levels rose only slightly from 34.1 pg/mL to 40.0 pg/mL P = .191). Average total androgens (testosterone plus dihydrotestosterone) rose in all patients to therapeutic levels, from 149.3 ng/dL to 642.1 ng/dL (P = .001). The ratio of total androgen to estradiol rose from 5.1 to 17.1 (P < .002). Luteinizing hormone was suppressed in the 6 patients for whom meaningful data were available, and decreased on average from 5.66 to 1.10 mIU/mL (P = .005) Lipid effects were measured, and a 15% drop in all cholesterol fractions was noted (P < .005). Evaluation of the questionnaire showed considerable improvements in sexual function and overall well-being in all but 1 patient. No adverse effects or nuisance-problems were detected during the duration of the study. CONCLUSION: Topically applied testosterone gels are an effective and convenient means of hormone replacement in hypogonadal men. PMID- 11206691 TI - A primary care approach to the infertile couple. AB - BACKGROUND: Approximately 20% of reproductive age couples have difficulty conceiving or maintaining an established pregnancy. The family physician is in a unique position to provide patient education, begin initial evaluation, make appropriate referrals, and offer ongoing counseling and support to couples who experience problems with fertility. METHODS: And extensive clinical review was conducted based on a MEDLINE search, the Cochrane database of systematic reviews, and other supporting evidence. RESULTS: Major physiologic influences affecting live birth rates include age, coital frequency, and duration of infertility. Male factor is associated with approximately 40% of these cases and should be addressed early in the evaluation. CONCLUSION: Many conditions once considered untreatable can now be routinely corrected. As managed care programs expand coverage to include infertility services, primary care providers will be asked to participate in the initial phase of this care. This article offers a practical approach. PMID- 11206692 TI - Crossing diagnostic borders: herpes encephalitis complicated by cultural and language barriers. AB - BACKGROUND: The patient who complains of vague mental status changes requires extra vigilance in that the underlying condition might itself affect the patient's ability to communicate well and relate a medical history. The differential diagnosis of delirium is broad, ranging from the benign to the potentially fatal. The diagnostic uncertainty inherent in primary care is compounded when language and cultural differences interfere with physician patient communication. METHODS: We undertook a MEDLINE-assisted review of the medical literature concerning herpes simplex encephalitis. Additionally, we performed an Internet search of several government Web sites to find current legal and federal guidelines concerning the use of medical interpreters. RESULTS AND CONCLUSIONS: We recount the case of a young Eastern European immigrant who complained initially of vague mental status changes and was found to have herpes simplex encephalitis. Diagnosis could have been made sooner had the physician been familiar with the patient's baseline mental status or had cultural and language barriers not stood between the physician and the patient and his mother. Herpes simplex encephalitis is a rare, but specific, cause of delirium for which prompt diagnosis and treatment with intravenous acyclovir can prevent death or serious sequelae. PMID- 11206693 TI - Screening for Strongyloides infection among the institutionalized mentally disabled. AB - BACKGROUND: Strongyloidiasis is an intestinal helminthic infection common among the mentally disabled population and can cause persistent occult infection before resulting in disseminated, possibly fatal disease. METHODS: Two cases of strongyloidiasis are described. The literature was searched using the key words "Strongyloides" and "mass screening." RESULTS AND CONCLUSION: Strongyloidiasis is clinically important and well documented in the mentally disabled populations both in endemic and nonendemic regions of North America. It has a substantial latent phase during which screening can be conducted, and its treatment with thiabendazole is convenient, effective, and reasonably well tolerated. Although strongyloidiasis is usually incidentally detected by findings of eosinophilia during routine blood screening, peripheral eosinophilia occurs only in 50% to 80% of infected persons and is extremely nonspecific for Strongyloides infection. Given the high cost of critical care for a patient with disseminated disease, screening mentally disabled populations in institutional settings for strongyloidiasis by administering the Strongyloides stercoralis antibody ELISA appears justifiable, particularly if risk factors for hyperinfection syndrome are used to select a subpopulation to be screened. PMID- 11206694 TI - Community-oriented primary care: historical perspective. AB - BACKGROUND: Community-oriented primary care (COPC) is a systematic approach to health care based upon principles derived from epidemiology, primary care, preventive medicine, and health promotion. We describe the development of COPC from an historical perspective. A critical assessment of current trends and implication for physician education and practice of COPC will be discussed in a companion article in the next issue of The Journal. METHODS: MEDLINE was searched using the key phrase "community-oriented primary care" Other sources of information included books and other documents. RESULTS AND CONCLUSIONS: In the 1950s, Sydney Kark showed dramatic positive changes in the health status of the population of Pholela, South Africa, using this approach. Similar approaches showed positive change in the health status of poor and underserved populations in the United States. The results were so impressive that the Institute of Medicine recommended widespread application of COPC in the United States. Successful COPC practices, however, have historically required considerable external funding from private and government sources. Thus, controversy about the feasibility of implementation of COPC in mainstream primary care practices developed. Schools of medicine and the discipline of family medicine have struggled to implement effective training in COPC within traditional medical school and residency structures. Yet, the societal need for recognition of and intervention in community health problems and coordination of community health resources continues. PMID- 11206695 TI - Mid-third femoral stress fracture with hip pain. PMID- 11206696 TI - Neonatal lupus erythematosus. PMID- 11206697 TI - Feasibility of using an alcohol-screening and health education system with older primary care patients. AB - BACKGROUND: This study evaluated the feasibility of a combined alcohol-screening and health education system for elderly patients METHODS: The Computerized Alcohol-Related Problems Survey (CARPS) was evaluated in primary care practices among 106 current drinkers, 60 years and older. The CARPS contains (1) a self administered screening survey; (2) software to scan or hand-enter survey responses; (3) software to process data and electronically generate reports of patients' drinking risks; (4) health education; and (5) a database useful for clinical and quality improvement purposes. RESULTS: Nearly all study participants were able to complete the CARPS while waiting for a prescheduled appointment with their physician. There were 44% of patients who were hazardous and 9% who were harmful drinkers. About 20% of men and 26% of women were binge drinkers. Most (85%) patients agreed that alcohol is an important topic, 67% reported learning new information, 78% had never discussed drinking with a physician, and 31% intended to do so. After reviewing CARPS data, physicians concluded that alcohol use in the elderly is an important quality improvement topic. CONCLUSIONS: Combined screening and health education systems appear feasible for use in practice if they deal with pertinent health problems such as alcohol use. Their data can encourage discussions between physicians and patients and might be used for quality improvement activities. PMID- 11206698 TI - Benzene-induced myelodysplastic syndrome. PMID- 11206699 TI - While you're waiting, let me introduce you to our computer. PMID- 11206700 TI - Family practice and emergency medicine. PMID- 11206701 TI - Pica and developmental disability. PMID- 11206702 TI - Dopamine D4 receptors and development of newer antipsychotic drugs. AB - The last ten years have witnessed the generation of a large amount of information on the neurobiology of dopamine receptors. Molecular biology and pharmacology studies have revealed existence of at least five dopamine receptor subtypes, namely D1, D2, D3, D4 and D5. The discovery of D4 receptors and the putative affinity of clozapine for D4 receptors have kindled development of selective D4 receptor antagonists for the treatment of schizophrenia. Studies on expression of D4 receptor proteins have shown selective localisation of D4 receptors in mesolimbic/mesocortical areas which could probably explain the lack of motor side effects with atypical antipsychotics like clozapine and olanzapine. However, neuropathological and genetic studies on the role of D4 receptors in the pathophysiology of schizophrenia and preliminary clinical studies with selective D4 receptor antagonists have been disappointing. There have been, however, complimentary findings between selective D4 receptor antagonism and genetic approaches such as antisense treatment or gene targeting. The therapeutic potential of D4 receptors as a target for developing antipsychotics will be known only when selective D4 receptor-antagonists with varying D2/D4 and D4/5-HT2A ratios are developed and tested in psychiatric patients. PMID- 11206703 TI - Angiotensin II type 1 receptor antagonist versus angiotensin I-converting enzyme inhibitor in experimental renal diseases. AB - Angiotensin II has an important role in the structural and functional regulation of the cardiovascular and renal systems. Blockade of the renin-angiotensin system can be achieved with angiotensin-converting enzyme (ACE) inhibitors and non peptidic, orally active, angiotensin II type I receptor (AT1) antagonists. However, the question that has yet to be answered is whether ACE inhibitors and AT1 receptor antagonists have similar renoprotective effects in various experimental diseases. Although many studies have assessed the role of either ACE inhibitors or AT1 receptor antagonists, we have reviewed the literature comparing both types of blocker in the same experiment. In most models of hypertension or renal failure, both classes of blocker appear to have similar antihypertensive and renal profiles. In a few models, the influence of the ACE inhibitor on arterial pressure and/or renal function is more marked than that of the AT1 receptor antagonist. Even though the maximum dose-effect curve for each compound was not often carried out for the systemic haemodynamics and renal alterations, the difference between both classes of blocker, when observed, appeared to favour the participation of non-angiotensin II or non-AT1-mediated mechanisms. Among them are the stimulation of prostaglandin production, kinin accumulation, nitric oxide generation and modulation of endothelin or TGFbeta1 expression via direct or indirect pathways. Future experimental and probably human studies aimed at comparing angiotensin II receptor antagonists and ACE inhibitors, with respect to blood pressure and renal damage, should be designed with all these concerns in mind. PMID- 11206704 TI - Pathophysiology of aldosterone and its antagonists. PMID- 11206705 TI - The protective effect of melatonin on cisplatin nephrotoxicity. AB - Regarding the mechanisms of cisplatin (CP) nephrotoxicity, several hypotheses have been put forward, among which oxidative stress (including depletion of glutathione and production of lipid peroxide) is noticeable. This investigation elucidates the role of the antioxidant system in CP-induced nephrotoxicity and the nephroprotection by melatonin. Balb/c mice were injected i.p. with: 1) vehicle control; 2) a single dose of 6.5 mg/kg cisplatin, CP group; 3) melatonin in a dose of 10 mg/kg for 5 days after CP injection, CP-M group; 4) melatonin (10 mg/kg) for 5 days before and after CP injection, M-CP-M group; 5) melatonin in a dose of 10 mg/kg for 5 days, M group. Mice were sacrificed 5 days after CP injection to determine blood urea nitrogen (BUN) and serum creatinine. Renal lipid peroxidation (LP) and glutathione (GSH) levels were evaluated in kidney homogenates. Cisplatin administration resulted in increased LP, BUN and serum creatinine levels and decreased GSH levels, whereas melatonin reversed these effects. Morphological kidney damage was apparent in the CP group. Mentioned degeneration was moderate in the CP-M group, whereas morphological findings of the M-CP-M group implied a well preserved kidney tissue. When M was administered alone, it didn't cause any significant change in biochemical parameters. Both C and M groups exhibited similar biochemical and morphological findings in light and transmission electron microscope observation. In conclusion, the present study suggests that melatonin may be of therapeutic benefit when used with CP. PMID- 11206706 TI - Protective effect of aminoguanidine in a murine model of pulmonary fibrosis induced by bleomycin. AB - Aminoguanidine is a drug known for more than a century, which has been attracting increasing interest in recent years due to the discovery of new pharmacological properties. This study investigated the effects of aminoguanidine on the fibrotic response induced by intratracheal administration of bleomycin to rats. Three groups of animals were studied: Group A (n = 19) corresponded to the control group. Group B (n = 20) received 10 IU/kg bleomycin intratracheal, and Group C (n = 12) received the same amount of bleomycin as Group B followed by 50 mg/kg/day aminoguanidine bicarbonate for 4 weeks. Aminoguanidine led to significant reductions in total hydroxyproline content of the lungs in Group C compared to Group B (Group A: 1.83+/-0.14 mg x Group B: 3.46+/-0.36 mg x Group C: 2.09+/-0.22 mg). Morphometric collagen studies carried out on histological sections stained with Sirius red F3BA showed that aminoguanidine promoted a significant reduction of the area occupied by collagen in the axial and septal zones of the lungs (Axial region = Group A: 4.29+/-1.31% x Group B: 19.30+/-4.86% x Group C: 8.52+/ 1.96%; Septal region = Group A: 0.15+/-0.06% x Group B: 0.61+/-0.21% x Group C: 0.15+/-0.06%). These results suggest that aminoguanidine is a potential therapeutic agent for the treatment and prevention of pulmonary fibrosis which is associated with different clinical conditions. PMID- 11206707 TI - Effects of zinc ions on Ca2+ uptake during histamine-induced contraction in guinea-pig taenia coli. AB - The present study was undertaken to clarify the effects of zinc ions (Zn2+) on Ca2+ uptake during histamine-induced contraction in guinea-pig taenia coli. Zn2+ (0.3 mM) had smaller effect on the initial phasic response to 10(-5) M histamine accompanied with decreased Ca uptake at the high affinity sites, while it inhibited the tonic response by inhibiting Ca2+ uptake at the low affinity sites. After the first stimulation with histamine in the presence of Zn2+, the Ca2+ binding at high affinity sites was not significantly recovered in the presence of Zn2+. A second stimulation with histamine in the presence of Zn2+ did not elicit any phasic response. Furthermore, after beta-escin treatment of the fibres, which leaves receptor-coupled signal transduction including the Ca2+ storage sites intact, the contraction due to 10(-5) M histamine was not so affected by 0.3 mM Zn2+, but, after resuspension in a solution of pCa 5, 10(-5) M histamine of second application did not elicit the contraction in the presence of Zn2+. These results suggested that Zn2+ does not affect the histamine-induced Ca2+ release from the intracellular storage sites in taenia coli. However, when Zn2+ is present, Ca2+ is not supplied to the storage sites for the phasic response due to second stimulation with histamine. In addition, Zn2+ reduced the tonic response to histamine mainly by inhibiting Ca2+ influx through receptor-operated and/or voltage-dependent Ca2+ channels. PMID- 11206708 TI - Interaction between the partially insurmountable antagonist valsartan and human recombinant angiotensin II type 1 receptors. AB - The interaction between the AT1 receptor-selective antagonist valsartan, and its human receptor, was investigated by direct radioligand binding as well as by its inhibition of angiotensin II induced inositol phosphate accumulation in CHO cells expressing human recombinant AT1 receptors. Specific binding of [3H]-valsartan rapidly reached equilibrium at 37 degrees C. It was saturable and occurred to a homogeneous class of sites with a K(D) of 0.88+/-0.076. It was inhibited by other AT1 receptor antagonists with the same potency order as previously described for the binding of [3H]-angiotensin II and [3H]-candesartan to human AT1 receptors (i.e. candesartan > or = EXP3174 > valsartan = irbesartan = angiotensin II > losartan). When valsartan and angiotensin II were applied simultaneously to the CHO-AT1 cells. the antagonist caused a rightward shift of the angiotensin II concentration response curve. Hence, valsartan interacts with the AT1 receptor in a manner that is competitive with angiotensin II. Pre-incubation of the cells with 0.5, 5 and 50 nM valsartan caused an additional, concentration-dependent, up to 55% decline of the maximal response. The partial nature of this insurmountable inhibition by valsartan was confirmed by biphasic antagonist concentration inhibition curves. These data reflect the co-existence of a fast reversible/surmountable as well as a tight binding/insurmountable valsartan receptor complex. In agreement, pre-incubation of the CHO-AT1 cells with 5 and 50 nM valsartan produced a partial inhibition of the angiotensin II induced increase of the free intracellular calcium concentration. [3H]-Valsartan dissociated from its receptors with a half-life of 17 min. In functional recovery experiments with valsartan-pre-treated cells, the angiotensin II-mediated response was half maximally restored within approximately 30 min. These kinetic data suggest that the insurmountable inhibition by valsartan is related to its relatively slow dissociation from the human AT1 receptors. PMID- 11206709 TI - Cardiovascular effects of chronic ifenprodil in a model of central sympathetic stimulation. AB - In the present study we investigated the effects of a long-term treatment (14 days) with ifenprodil on the excitatory haemodynamic responses induced by central pharmacological stimulation in anaesthetised rabbits. The intracerebroventricular injection of L-glutamate (3 mg/kg) induced important rises in dP/dtmax (32.9%), mean arterial pressure (42.6%) and in the myocardial oxygen consumption index: the triple product (84.2%). Ifenprodil (1.5, 3 and 6 mg/kg/day, i.p.) reduced the increases in myocardial oxygen demand induced by intracerebral L-glutamate in a dose-related manner. Interestingly, ifenprodil also reduced in a dose-dependent manner the maximum values of the oxygen demand indices reached during the central nervous system stimulation. These results indicate that the long-term treatment with ifenprodil can reduce the myocardial oxygen consumption induced by central nervous system stimulation without significant depression of the resting cardiac function. This favourable effect of ifenprodil is in fact a consequence of the association of mild inhibitory effects on the three parameters taken into account in the triple product index of myocardial oxygen consumption. PMID- 11206711 TI - Ursodeoxycholic acid modulates cyclosporin A oral absorption in liver transplant recipients. AB - The aim was to study the ursodeoxycholic acid (UDC) effect on the cyclosporin A (CsA) pharmacokinetics after oral administration of the microemulsion formulation Neoral (CsA-ME) in liver transplant recipients, and test the potential protective effect of this bile acid on liver and renal CsA-ME-induced toxicity. At entry into the study, 12 patients who underwent orthotopic liver transplantation received CsA-ME, for at least 6 months. They then received a cotreatment CsA-ME plus UDC (13.8 mg x kg(-1) x day(-1)) for three months. Blood concentrations of CsA were measured using a monoclonal antibody specific for the parent compound. The kinetic data were analysed by a mathematical model incorporating a time dependent rate coefficient for CsA intestinal absorption, before and after UDC treatment. Changes in serum markers of hepatic and renal injury were assessed. Individual serum bile acids were determined by chromatography. Serum levels of UDC increased from 3 to about 45% of total serum bile acids after UDC treatment. The estimated model parameters indicate that UDC administration modulates CsA intestinal absorption. In the nine non-cholestatic patients, UDC reduced the absorption rate and the bioavailability of CsA without modifying the elimination rate constant of CsA and the CsA pre-drug levels. In contrast, in the three cholestatic patients, the bioavailability tended to be higher and the absorption rate faster when CsA was combined with UDC. UDC significantly decreased elevated gamma-glutamyl transferase and creatinine serum levels and induced some clinical improvements such as disappearance of headaches in four patients. In conclusion, a 3-month UDC treatment modifies CsA intestinal absorption without affecting CsA elimination rate constant. On the other hand, UDC supplementation appears to improve CsA tolerability. PMID- 11206710 TI - Effect of lipopolysaccharide treatment on neurogenic contraction and noradrenaline release in rat arteries. AB - In the present study, contractile responses and [3H]-noradrenaline overflow evoked by electrical field stimulation were assessed, respectively, in the small mesenteric artery and in tail artery removed from rats pre-treated with either saline or lipopolysaccharide (LPS). In small mesenteric arteries, LPS treatment did not significantly modify the contractile responses elicited by electrical stimulation, in the absence or in the presence of L-arginine. However, in arteries removed from rats treated with LPS, L-arginine addition produced relaxation of vessels pre-contracted with noradrenaline. The amplification of neurogenic contraction by the nitric oxide (NO) synthase inhibitor Nomega-nitro-L arginine methyl ester (L-NAME) was similar in arteries removed from saline and LPS-infused rats. In mesenteric arteries, LPS treatment suppressed the potentiation of the neurogenic responses by the alpha2-adrenoceptor antagonist, yohimbine and by the inhibitor of neuronal uptake of noradrenaline, cocaine. In rat tail artery exposed to L-arginine, LPS treatment produced an increase in [3H] noradrenaline overflow evoked by electrical stimulation. Altogether, these data suggest that an enhanced noradrenaline release from sympathetic nerves, probably resulting from inhibition of the modulatory effect of both prejunctional alpha2 adrenoceptors and neuronal uptake mechanism, may play a role in the preservation of neurogenic response after LPS treatment despite evidence of the induction of NO synthase. PMID- 11206712 TI - Calcium and bicarbonate ions mediate the inhibition of mast cell histamine release by Avene spa water. AB - Avene spa water (ASW) inhibits the histamine release induced in mast cells by substance P; the inhibition is reversed by EDTA and by EGTA. Calcium and magnesium ions, the major cations present in ASW, were experimented in simple saline solutions in the presence of various counter-ions. Only calcium salts inhibited the peptidergic stimulation, with different potencies ruled by the nature of the counter-anion (HCO3- > Cl- > SO4(2)). On a Ca2+ concentration basis, ASW was, however, more inhibitory, suggesting that other compounds present in ASW potentiate the effect of calcium. PMID- 11206713 TI - Pharmacogenomics and therapeutic target validation in cerebral vasospasm. AB - One of the most important pharmacogenomic technologies is transcriptome analysis. We used this method to study the change of gene expression profiles in animal models of cerebral vasospasm. We found novel drug target candidates in cerebral vasospasm through pharmacogenomics. By using differential display and quantitative reverse transcriptase-polymerase chain reaction, we found that heme oxygenase-1 (HO-1) mRNA was prominently induced in the basilar artery and modestly in brain tissue in a murine vasospasm model. There was a significant correlation between the degree of vasospasm and HO-1 mRNA levels in the basilar arteries exhibiting vasospasm. Antisense HO-1 oligodeoxynucleotides (ODN) inhibited HO-1 induction in the basilar arteries, but not in the whole brain tissue. This phenomenon was not observed in the nontreatment, sense HO-1 ODN and scrambled ODN treatment arteries. We report, for the first time, the protective effects of HO-1 gene induction by endogenous or clinical compounds in cerebral vasospasm after subarachnoid hemorrhage, a finding that should provide a novel therapeutic target for cerebral vasospasm. PMID- 11206714 TI - Long-term regulation of catecholamine formation by ouabain in cultured bovine adrenal chromaffin cells. AB - The long-term effects of ouabain, an inhibitor of Na+/K+ -ATPase, on catecholamine formation in cultured bovine adrenal chromaffin cells were examined. The increase in [14C]catecholamine formation from [14C]tyrosine induced by ouabain was dependent on incubation time, and its maximal effect was observed after incubation for 8 h. The stimulatory effect of ouabain was concentration dependent (10-300 nM), causing maximal stimulation at 300 nM. The formation of [14C]catecholamines induced by ouabain was not increased by incubation with [14C]DOPA instead of [14C]tyrosine. Ouabain-induced [14C]catecholamine formation was influenced by decreases in extracellular Ca2+ concentration, but not by the presence of cycloheximide or actinomycin D. These results suggested that ouabain stimulates continuous activation of hydroxylation of tyrosine through a Ca2+ dependent mechanism in cultured bovine adrenal chromaffin cells. PMID- 11206716 TI - Dystrophin disruption might be related to myocardial cell apoptosis caused by isoproterenol. AB - Sarcolemma integrity is stabilized by the dystrophin-associated glycoprotein complex that connects actin and laminin-2 in contractile machinery and the extracellular matrix, respectively. Interruption of the connection by the primary gene defect or acquired pathological burden can cause cardiac failure. The purposes of the present study were to verify whether dystrophin is disrupted in acute myocardial injury after the isoproterenol overload (10 mg/kg) and to examine its relation to myocardial cell apoptosis in rats. This injury from 4-16 h at the subendocardium was accompanied by dystrophin disruption and dislocation from subsarcolemma to cytoplasm, which were confirmed by immunohistology and Western blotting. However, delta-sarcoglycan was thoroughly preserved in sarcolemma. The dystrophin degradation preceded the appearance of apoptotic cells and exactly coincided with the transferase-mediated dUTP-biotin nick end labeling positive cardiomyocytes (TUNEL), as was verified by double-staining. These data suggest that beta-adrenergic stimulation induces dystrophin breakdown followed by apoptosis. PMID- 11206715 TI - Carvedilol enhances atrial and brain natriuretic peptide mRNA expression and release in rat heart. AB - To clarify the role of the natriuretic peptide (NP) system in the myocardial protective effects of carvedilol, a beta-blocking agent, we investigated the effects of carvedilol on the NP system in the rat heart. After oral administration of carvedilol (low-dose group: 2 mg/kg/day, group C2; high-dose group: 20 mg/kg/day, group C20) for 1 week, plasma rat atrial NP (r-ANP), atrial mRNA levels of ANP, left ventricular mRNA of brain NP (BNP), NP receptor-A and NP receptor-C (NPR-C) (as a clearance receptor) were measured. Values were compared with those in vehicle-treatment rats (group V). The concentration of r-ANP was significantly higher in group C2 (135 +/- 9 pg/ml) and group C20 (161 +/- 11 pg/ml) than group V (75 +/- 6 pg/ml; both p < 0.01). ANP and BNP mRNA levels were significantly increased and NPR-C was significantly down regulated in group C2 (151 +/- 7, 120 +/- 8 and 78 +/- 7%, respectively, vs. group V) and group C20 (164 +/- 8. 133 +/- 7 and 72 +/- 8%, respectively, vs. group V) compared with group V (all p < 0.01). These results suggest that not only a high dose, but a low dose of carvedilol has the effect of increasing plasma ANP and BNP levels. This effect was closely related to the upregulation of ANP and BNP mRNA expression, and the down regulation of NPR-C mRNA expression in the heart. These mechanisms seem to account for a sizable portion of the protective effect of carvedilol for heart diseases. PMID- 11206717 TI - Chronic adriamycin treatment impairs myocardial interstitial neuronal release of norepinephrine and epinephrine. AB - Although chronic adriamycin (doxorubicin) treatment is known to induce cardiomyopathic heart failure with sympathetic neurohumoral activation in a dose dependent manner, its effect on local neuronal catecholamine release at the cardiac sympathetic nerve terminals remains to be clearly determined. Using a cardiac microdialysis technique, we measured dialysate norepinephrine (NE) and epinephrine (Epi) concentrations as indices of myocardial interstitial NE and Epi levels. respectively, in rabbits with chronic adriamycin treatment (ADR) (4 mg/kg/week, 6 weeks, n = 8) and in control rabbits (CNT) (n = 6). Exocytotic release was evoked by the local administration of KCl (100 mM) through the dialysis probe. Basal levels of NE and Epi did not differ between the ADR and CNT groups (NE, 11.6 +/- 6.6 vs. 20.4 +/- 17.2 pg/ml; Epi, 4.0 +/- 0.1 vs. 4.6 +/- 1.7 pg/ml: mean +/- SD). The exocytotic release was suppressed in the ADR compared with the CNT group (NE, 191.4 +/- 144.7 vs. 760.5 +/- 337.8 pg/ml; p < 0.05: Epi, 4.2 +/- 0.4 vs. 20.8 +/- 9.9 pg/ml; p < 0.05). We conclude that chronic adriamycin treatment impairs the neuronal exocytotic release of catecholamine at the cardiac sympathetic nerve terminals. PMID- 11206718 TI - Norepinephrine release is increased in the hibernating heart, studied in a chronic canine model of myocardial hibernation. AB - We examined the change in cardiac sympathetic function in the hibernating heart. To induce hibernating hearts in dogs, we placed a nylon tube via the carotid artery in the left circumflex artery (LCx) and obstructed the LCx flow. The plasma norepinephrine (NE) and epinephrine (E) concentrations in the coronary sinus and the aorta were measured before and 1 week after the tube placement to evaluate the catecholamine release from the heart. The wall motion was followed by echocardiography and. 1 week after the tube placement, regional myocardial blood flow (RBF) was measured using colored microspheres. Also. the restorability of myocardial dysfunction was examined in other dogs by extracting the LCx tube 1 week after the placement. Finally, the heart was removed for pathological observation and dogs showing myocardial infarction were excluded. One week after placing the tube, wall thickening was reduced in the LCx area, but was not in the left anterior descending (LAD) area. Compared with the LAD area, RBF in the LCx area was decreased in the endocardium (p < 0.05), but was not in the epicardium. In other dogs, the reduced wall thickening in the LCx area was restored to normal levels 1 or 2 weeks after the tube extraction. Thereby, our dogs with the tube placed were considered to be models of myocardial hibernation. The plasma NE and E concentrations were not significantly changed by placing the tube, but NE release from the heart was increased after the tube placement (p < 0.05). E uptake from the heart did not differ. Therefore, it is suggested that NE release is increased in the hibernating heart and may contribute to its mechanism. PMID- 11206719 TI - Beneficial effect of angiotensin-converting enzyme inhibitor on dilated cardiomyopathy induced by autoimmune mechanism against beta1-adrenoceptor. AB - We have shown that a peptide corresponding to the sequence of the second extracellular loop of the human beta1-adrenoceptor (beta1-peptide) was able to induce an autoimmune cardiomyopathy in rabbits. In this study, we examined the effect of angiotensin-converting enzyme inhibitor (ACEI) on beta1-peptide-induced cardiomyopathy. Rabbits were divided into four groups: (1) control group (n= 6) receiving saline injection; (2) beta1-peptide group (n = 8) immunized with beta1 peptide; (3) ACEI group (n = 6), lisinopril (3 mg/day) given orally and receiving saline injection; and (4) ACEI + beta1-peptide group (n = 7), lisinopril (3 mg/day) given orally and immunized with beta1-peptide. Our results showed that, after 1 year, all rabbits in the beta1-peptide group had an increase in heart weight, wall thinning and dilatations of both ventricles as compared with rabbits in the ACEI + beta1-peptide group that had normal heart weight and shape. All rabbits in the beta1-peptide group exhibited multifocal degeneration and necrosis of myocardial cells with moderate infiltration of inflammatory cells. In the ACEI + beta1-peptide group, three rabbits showed focal degeneration and necrosis of myocardial cells accompanied by mononuclear cells. The lesions in this group were apparently less marked than those in the beta1-peptide group. In conclusion, ACEI protects the myocardium from injury induced by an autoimmune mechanism against beta1-adrenoceptor. PMID- 11206720 TI - Acute effects of endothelin-1 and TAK-044 (ET(A) and ET(B) receptor antagonist) in rats with dilated cardiomyopathy. AB - The hemodynamic effects of endothelin (ET)-1 and TAK-044 (ET(A) and ET(B) receptor antagonist) were studied in a rat model of dilated cardiomyopathy after autoimmune myocarditis. Six weeks after immunization, survived Lewis rats (30/43 = 70%) were randomly allocated into five groups to be given 0, 0.3, 3, 30 and 60 mg/kg/day (groups F0, F0.3, F3, F30 and F60; each group, n = 4) of TAK-044 using an osmotic pump subcutaneously. Age-matched normal Lewis rats (n = 26) were also randomly divided into four groups to be given 0, 0.3, 3 and 30 mg/kg/day (groups N0, N0.3, N3 and N30; each group, n = 4). ET-1 concentrations in plasma and myocardium were measured, and immunohistochemical detection of ET-1 in the left ventricle from the remaining rats (groups F and N) was performed. After administration of TAK-044 for 7 days, 2, 4, 11, 21 and 42 ng/min ET-1 every 20 min was infused using a pump, and the change in mean arterial pressure of each group during the infusion was examined. The plasma and myocardial ET-1 concentrations were significantly higher in group F than group N (12.3 +/- 1.5 vs. 5.4 +/- 0.2 pg/ml and 426 +/- 31 vs. 98 +/- 6 pg/g tissue; both p < 0.01). Strong positive signals for ET-1 were found to be widely distributed in the left ventricular myocardium of both groups of rats. Although the ET-1-induced increase in the mean arterial pressure was abolished in group N30, the maximal dose of ET 1 produced a 34% increase in the mean arterial pressure in group F30. Even in group F60, ET-1-induced hypertension was blocked incompletely. These results indicate that the heart may be a major ET-1-producing organ, and a higher dose of ET-1 antagonist is needed to block the effect of ET-1 in rats with dilated cardiomyopathy. PMID- 11206721 TI - Differential effects of omega-conotoxin GVIA, tetrodotoxin and prolonged cold storage on purinergic and adrenergic transmission in isolated canine splenic artery. AB - Double-peaked vasoconstrictions (biphases of vasoconstrictions) were readily induced in the conditions of 30 s trains of pulses at 1 Hz in the isolated, perfused canine splenic artery. P2X purinoceptors have previously been shown to be involved mainfy in the first-peaked response and alpha1-adrenoceptors mostly in the second. The treatment with 10 nM omega-conotoxin GVIA (omega-CTX) produced a parallel inhibitory effect on the first- and second-peaked vasoconstrictor responses to nerve stimulation. A submaximal concentration of tetrodotoxin (TTX) (3 nM) did not affect the first peak of constriction, but strongly inhibited the second peak, although a larger dose of TTX (30 nM) abolished either the first- or second-peaked response. On the other hand, after cold storage at 4 degrees C for 7 days, the first-peaked vasoconstriction markedly decreased, whereas the second peaked response was not significantly modified. IN CONCLUSION: (1) omega-CTX sensitive calcium channels may produce a parallel modulation of purinergic and adrenergic components of sympathetic cotransmission; (2) TTX-sensitive sodium channels may have a more important role in controlling the adrenergic rather than purinergic transmission; and (3) the function of purinergic transmission of sympathetic nerve might be affected more strongly than that of adrenergic transmission in the cold-stored canine splenic artery. PMID- 11206722 TI - Effect of inhaled nitric oxide on cardiovascular response to catecholamine in heart failure. AB - We examined the dose responses to continuous infusion of isoproterenol (ISO) and norepinephrine (NE) in normal (control) and procainamide-induced heart failure dogs with or without inhalation of 70 ppm nitric oxide (NO). Inhaled NO affected neither left ventricular (LV) function nor hemodynamics at baseline in both control and heart failure dogs. There were no significant differences in the responses to ISO and NE with or without inhaled NO in the control. The responses of LV dP/dt to ISO and NE were significantly enhanced in heart failure; however, they were not affected by inhaled NO. In contrast, LV pressure and dimension at end diastole were significantly increased, and pulmonary vascular resistance (PVR) was significantly decreased by inhaled NO during infusion of both ISO and NE in heart failure. In conclusion, the positive inotropic response to cathecholamine is not affected by inhaled NO even in heart failure. Inhaled NO decreases PVR, but potentially increases LV preload in the presence of additional stress of cathecholamine in heart failure. PMID- 11206723 TI - Role of the parasympathetic nervous system and interaction with the sympathetic nervous system in the early phase of hypertension. AB - The role of the peripheral parasympathetic nervous system in the development of hypertension was investigated in spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats. Animals were 5-7 weeks old, anesthetized, and in the open-chest condition. The decrement in heart rate evoked by parasympathetic nerve stimulation (62 +/- 8 beats/min) in SHR was greater (p < 0.01) than that in WKY rats (23 +/- 4 beats/min). Furthermore, the decrease in heart rate (73 +/- 9 beats/min) in response to combined stimulation of sympathetic and parasympathetic nerves in SHR was greater (p < 0.05) than that in response to vagal stimulation alone. The extent of the interaction of sympathetic and parasympathetic nerves was calculated as the difference between the decrease in heart rate during combined stimulation and that during vagal nerve stimulation alone. The extent of the interaction in SHR (-11 +/- 5) was not significantly different from that in WKY rats (-8 +/- 3 beats/min). Therefore, the influence of the peripheral parasympathetic nervous system in the early phase of hypertension may be greater than that in the normotensive state. Interaction between the two branches of the autonomic nervous system may occur as accentuated antagonism originating in the early phase of hypertension. The interaction during the early phase of hypertension may not be different in extent from that of the normotensive state. PMID- 11206724 TI - Effects of beta-endorphin on norepinephrine release in hypertension. AB - Recent studies have suggested an involvement of the endogenous opioid system in blood pressure control. The purpose of the present study was to determine the role of beta-endorphin in the regulation of sympathetic nervous activity in the central nervous system of hypertension. The effects of beta-endorphin on the electrically evoked release of [3H]norepinephrine (NE) were investigated in superfused slices of rat medulla oblongata. Beta-endorphin inhibited the stimulation-evoked NE release in a dose-dependent manner in rat medulla oblongata. In the medulla oblongata of spontaneously hypertensive rats (SHR), the inhibitory effect of beta-endorphin on the stimulation-evoked NE release was significantly smaller than in the medulla oblongata of Wistar-Kyoto rats. These results showed that beta-endorphin might reduce NE release in rat medulla oblongata. Furthermore, the lesser inhibitory effect of beta-endorphin on NE release in SHR might suggest that the opioid peptide could be involved in the regulation of central sympathetic nervous activity in hypertension. PMID- 11206725 TI - Conserved smooth muscle contractility and blood pressure increase in response to high-salt diet in mice lacking the beta3 subunit of the voltage-dependent calcium channel. AB - Voltage-dependent calcium channels are crucially important for calcium influx and the following smooth muscle contraction. Beta subunits of these channels are known to modify calcium currents through pore-forming alpha subunits. Among the four reported independent beta subunits, the beta3 subunit is expressed in smooth muscle cells and thought to compose L-type calcium channels in the tissue. To determine the role of the beta3 subunit in the cardiovascular system, we have analyzed beta3-null mice. Electrophysiological examinations proved the existence of dihydropyridine (DHP)-sensitive. L-type calcium channels in the smooth muscle cells. Beta3-null mice show no apparent changes in smooth muscle contraction and sensitivity to DHP, and normal blood pressure when they are raised on a normal diet, but the 13 subunit deficient mice show elevated blood pressure in response to a high-salt diet, with significant reductions in plasma catecholamine concentrations. Our finding strongly suggests a close relationship between voltage-dependent channels and high blood pressure. PMID- 11206726 TI - A dopamine-secreting pheochromocytoma. AB - We describe a patient with pheochromocytoma, which secretes dopamine. He was admitted to hospital because of chronic diarrhea. After surgical resection of the tumor, dramatic cessation of the diarrhea and blood pressure elevation were observed. Decreased expression of dopamine beta-hydroxylase in the tumor was considered a possible mechanism of producing a pathophysiological concentration of dopamine. This case shows that excessive excretion of dopamine, a vasodilative hormone, may affect blood pressure. PMID- 11206727 TI - Heart rate and plasma cyclic AMP responses to isoproterenol infusion and effect of beta-adrenergic blockade in patients with postural orthostatic tachycardia syndrome. AB - To clarify the pathophysiological mechanism of postural orthostatic tachycardia syndrome (POTS). the responses of heart rate and the plasma cyclic AMP (cAMP) level to isoproterenol infusion in the supine position were evaluated in 10 POTS patients and 10 age-matched controls. Also, the effect of beta-adrenergic blockade on POTS was assessed using the headup tilt test. The POTS patients consisted of two men and eight women, with a mean age of 19.7 years (range. 15-28 years). An exaggerated increase of both heart rate and the plasma cAMP concentration after isoproterenol infusion at a low dose (1 microg/min) was observed in the POTS patients, but not in control subjects. Seven POTS patients received oral beta-blocker therapy. In five of these, symptoms were abolished and there was a smaller heart rate increase during the head-up tilt test. These data suggest that POTS may be more prevalent in young women and that beta-adrenergic hypersensitivity may play a role in the mechanisms of this syndrome. However, a larger series of patients need to be studied in the future. PMID- 11206728 TI - Effect of a hypocaloric diet on adrenomedullin and natriuretic peptides in obese patients with essential hypertension. AB - We examined the effect of a hypocaloric diet on adrenomedullin (AM), atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) in 12 obese patients with essential hypertension (age, 48-81 years; body mass index, 26-34 kg/m2). For the initial week, a standard diet of 2000 kcal/day was given, followed by 3 weeks of a hypocaloric diet of 850 kcal/day, with a constant intake of sodium. The patients lost 3.7 +/- 0.2 kg body weight during the hypocaloric diet period (p < 0.0001). The decrease in blood pressure during the study period was 10.3 +/- 3.6 mmHg systole (p = 0.017) and 4.2 +/- 3.2 mmHg diastole (NS). Plasma AM concentration was decreased significantly from 4.88 +/- 0.46 to 3.97 +/ 0.38 pmol/l by the hypocaloric diet (p = 0.004). Plasma ANP and BNP concentrations were also decreased significantly by the hypocaloric diet (p = 0.042 for each). These results demonstrate, for the first time, that plasma AM concentration as well as plasma ANP and BNP concentrations are decreased by a hypocaloric diet in obese patients with essential hypertension. These vasodilator peptides may act against further elevation in blood pressure in obese patients with essential hypertension. PMID- 11206729 TI - Therapeutic use of dopamine and beta-blockers modulates plasma interleukin-6 levels in patients with congestive heart failure. AB - We previously reported that the spillover of interleukin-6 (IL-6) into the peripheral circulation increases with the severity of congestive heart failure (CHF), and that the increase is mainly associated with activation of the endogenous sympathetic nervous system. However, the role of the sympathetic nervous system in the increase of IL-6 in CHF patients is not yet fully understood. To address this question, we measured plasma IL-6 levels before and after therapeutic administration of dopamine and betablockers in patients with CHF. After more than 24 h (mean, 34 h) of treatment with a low dose of intravenous dopamine (mean, 2.4 microg/kg/min) in 1 patients with dilated cardiomyopathy and deterioration of CHF, the plasma IL-6 level was increased significantly (30.8 vs. 16.6 pg/ml; p = 0.003) despite the improved hemodynamics. After 377 days of beta-blocker therapy in 24 patients with dilated cardiomyopathy, the plasma IL-6 level was decreased significantly (2.04 vs. 3.11 pg/ml; p = 0.01) along with the improvement of symptoms, left ventricular ejection fraction, and neurohumoral factors. Dopamine increases and beta-blockers decrease the plasma IL-6 level in patients with CHF, suggesting that drugs modulating the sympathetic nervous system may alter IL-6 in these patients. PMID- 11206730 TI - Biphasic inotropic response to endothelin-1 in the presence of various concentrations of norepinephrine in dog ventricular myocardium. AB - The present study was undertaken to investigate the interaction between endothelin-1 (ET-1) and norepinephrine (NE) on contractile regulation in dog ventricular myocardium. ET-1 alone did not elicit any inotropic response in isolated dog ventricular trabeculae (37 degrees C, 0.5 Hz). In the presence of NE at a high concentration (10(-7) M), ET-1 (10(-8) M) elicited a long-lasting negative inotropic effect, while in the presence of NE at a moderate concentration (3 x 10(-8) M) it produced a biphasic inotropic effect: a sustained positive inotropic effect subsequent to a short-lasting negative inotropic effect. In the presence of a lower concentration (10(-9) M) that affected scarcely the basal force of contraction, ET-1 produced a pronounced positive inotropic effect in association with negative lusitropic and negative clinotropic effects in a concentration-dependent manner subsequent to a small transient negative inotropic effect. The presented results indicate that not only the extent, but also the quality of the inotropic response to ET-1 is determined by the level of NE in the biophase. The crosstalk of ET-1 with NE may play a crucial role in pathophysiological regulation of cardiac contractility in intact dog ventricular myocardium. PMID- 11206731 TI - Diseases of the eye of farmed shrimp Penaeus monodon. AB - Lesions were found in the eyes of cultured shrimp Penaeus monodon that displayed non-specific signs of disease, including lethargy, dark pigmentation, brown gills, empty midgut, anorexia, white tail muscle, necrosis of uropods and fouled cuticle. Eye lesions were associated with sexual development in moribund shrimp in at least 1 disease event. Suppurative inflammation, granuloma and malacia were observed in histological examination of the eye and the causative agents of lesions appear to be Vibrio spp. and a rod-shaped virus (similar to Lymphoid Organ Virus, Gill-Associated Virus [GAV] and Yellow-Head Virus). Suppurative inflammation was characterised by edema, infiltration of haemocytes and local sites of abscesses. Eyes with granuloma usually appeared white in pond-side examinations, and histology showed that fibrous tissue replaced ommatidia, ganglia and internal structures of the eye. Malacia of the eye was characterised by necrosis of nervous tissue, vacuolation and vascular proliferation in the medulla ganglia. Levels of presumptive Vibrionaceace were high in moribund specimens and Gram-negative rods were observed in some specimens as free particles in the interstitial fluid and haemolymph in the eye. Transmission electron microscopy showed that nerve cells in the fasciculated zone (near the basement membrane) contained cytoplasmic vesicles (1 to 3 microm in diameter) with particles (15 to 26 nm in diameter) and rod-shaped nucleocapsids. The rods were similar to those of GAV and were 130 to 260 nm long, 10 to 16 nm in diameter and had helical symmetry with a screw-like thread (2.4 to 3.5 nm pitch). Also, unidentified enveloped virions, averaging 74 nm in diameter, were observed in cytoplasmic vesicles in the fasciculated zone. In conclusion, it is suggested that bacterial and viral infections of the eye could result in impaired neuroendocrine functions, which may cause a range of clinical signs of disease. PMID- 11206732 TI - Identification of genomic variations among geographic isolates of white spot syndrome virus using restriction analysis and Southern blot hybridization. AB - White spot syndrome virus (WSSV) is widely distributed in most of the Asian countries where penaeid shrimp are cultured, as well as in some regions of the USA. Six geographic isolates of WSSV-1 each from penaeid shrimp from China, India, Thailand, and the US states of Texas and South Carolina, and 1 isolated from crayfish at the National Zoological Park in Washington, DC-were compared by combining the methods of restriction analysis and Southern blot hybridization. DNA was extracted from purified viruses and then digested with selected endonucleases: AccI, BglII, ClaI, BamHI, EcoRI, HindII, HaeI, SacI and XhoI. The blots were detected with digoxigenin-11-dUTP-labeled WSSV genomic probes: LN4, C42 and A6. No distinctive differences among the 5 WSSV isolates from penaeid shrimp were detected; however, differences in the WSSV isolate from crayfish were observed. A 2.8 kb DNA fragment originating from the crayfish isolate and encompassing the LN4 region was subcloned into pBluescript and sequenced for comparison with the LN4 fragment from the Thailand WSSV isolate. The results indicate that some genomic components of WSSV from different geographic regions share a high degree of homology. This method can be used to distinguish between the WSSV isolate from crayfish and the WSSV isolates from penaeid shrimp. PMID- 11206733 TI - Isolation in cell culture of nodavirus from farmed Atlantic halibut Hippoglossus hippoglossus in Norway. AB - Isolation in cell culture of nodavirus from Atlantic halibut Hippoglossus hippoglossus suffering from viral encephalopathy and retinopathy (VER) is described. The cell line SSN-1 was inoculated with tissue material from affected juveniles (60 d after first feeding). Extensive cytopathic effects (CPE) developed approximately 5 d after inoculation, and were also observed after several passages in the same cell line. Cells from infected cultures showed reactivity with an antiserum against sea bass Dicentrarchus labrax nodavirus in an indirect immunofluorescence test. Analysis of infected cells with reverse transcriptase-polymerase chain reaction (RT-PCR) resulted in a product of the predicted size using primers specific for striped jack Pseudocaranx dentex nodavirus. Electron micrographs of infected SSN-1 cells demonstrated virus particles that were approximately less than 30 nm. Challenge of Atlantic halibut larvae (4 d post-hatching) with supernatants from infected SSN-1 cells resulted in development of VER as verified by immunohistochemistry performed on larvae sampled from Day 9 after challenge. The present results show that a nodavirus from Atlantic halibut has been isolated using the SSN-1 cell line and that virus propagated in cell culture retained virulence. PMID- 11206734 TI - Characterization of a virus obtained from snakeheads Ophicephalus striatus with epizootic ulcerative syndrome (EUS) in the Philippines. AB - This is the first report of the isolation and characterization of a fish virus from the Philippines. The virus was isolated using snakehead spleen cells (SHS) from severely lesioned epizootic ulcerative syndrome (EUS)-affected snakehead Ophicephalus striatus from Laguna de Bay, in January 1991. The virus induced cytopathic effects (CPE) in SHS cells yielding a titer of 3.02 x 10(6) TCID50 ml( 1) at 25 degrees C within 2 to 3 d. Other susceptible cell lines included bluegill fry (BF-2), catfish spleen (CFS) and channel catfish ovary (CCO) cells. Replication in chinook salmon embryo cells (CHSE-214) was minimal while Epithelioma papulosum cyprini cells (EPC) and rainbow trout gonad cells (RTG-2) were refractory. Temperatures of 15 to 25 degrees C were optimum for virus replication but the virus did not replicate at 37 degrees C. The virus can be stored at -10 and 8 degrees C for 30 and 10 d, respectively, without significant loss of infectivity. Viral replication was logarithmic with a 2 h lag phase; viral assembly in the host cells occurred in 4 h and release of virus occurred 8 h after viral infection. A 1-log difference in TCID50 titer between the cell-free virus and the total virus was noted. Freezing and thawing the virus caused a half log drop in titer. Viral exposure to chloroform or heating to 56 degrees C for 30 min inactivated the virus. Exposure to pH 3 medium for 30 min resulted in a more than 100-fold loss of viral infectivity. The 5-iododeoxyuridine (IUdR) did not affect virus replication, indicating a RNA genome. Neutralization tests using the Philippine virus, the ulcerative disease rhabdovirus (UDRV) and the infectious hematopoietic necrosis virus (IHNV) polyvalent antisera showed slight cross reaction between the Philippine virus antiserum and UDRV but established no serological relationship with SHRV and IHN virus. Transmission electron microscopy (TEM) of SHS cells infected with the virus showed virus particles with typical bullet morphology and an estimated size of 65 x 175 nm. The Philippine virus was therefore a rhabdovirus, but the present study did not establish its role in the epizootiology of EUS. PMID- 11206735 TI - Mortality and kidney histopathology of chinook salmon Oncorhynchus tshawytscha exposed to virulent and attenuated Renibacterium salmoninarum strains. AB - An isolate of Renibacterium salmoninarum (strain MT 239) exhibiting reduced virulence in rainbow trout Oncorhynchus mykiss was tested for its ability to cause bacterial kidney disease (BKD) in chinook salmon Oncorhynchus tshawytscha, a salmonid species more susceptible to BKD. Juvenile chinook salmon were exposed to either 33209, the American Type Culture Collection type strain of R. salmoninarum, or to MT 239, by an intraperitoneal injection of 1 x 10(3) or 1 x 10(6) bacteria fish(-1), or by a 24 h immersion in 1 x 10(5) or 1 x 10(7) bacteria ml(-1). For 22 wk fish were held in 12 degrees C water and monitored for mortality. Fish were sampled periodically for histological examination of kidney tissues. In contrast to fish exposed to the high dose of strain 33209 by either injection or immersion, none of the fish exposed to strain MT 239 by either route exhibited gross clinical signs or histopathological changes indicative of BKD. However, the MT 239 strain was detected by the direct fluorescent antibody technique in 4 fish that died up to 11 wk after the injection challenge and in 5 fish that died up to 20 wk after the immersion challenge. Viable MT 239 was isolated in culture from 3 fish that died up to 13 wk after the immersion challenge. Total mortality in groups injected with the high dose of strain MT 239 (12%) was also significantly lower (p < 0.05) than mortality in groups injected with strain 33209 (73 %). These data indicate that the attenuated virulence observed with MT 239 in rainbow trout also occurs in a salmonid species highly susceptible to BKD. The reasons for the attenuated virulence of MT 239 were not determined but may be related to the reduced levels of the putative virulence protein p57 associated with this strain. PMID- 11206736 TI - A new strain of Cryptocaryon irritans from the cultured olive flounder Paralichthys olivaceus. AB - An obligate parasite, Cryptocaryon irritans, which is responsible for the white spot disease of marine fish is known to develop in the temperature regime over 19 degrees C. Recently, however, we found white spot disease of olive flounder Paralichthys olivaceus during winter at water temperatures ranging between 12 and 16 degrees C in Korea. In the present study we isolated a C. irritans-like ciliate from the affected fish and investigated its reproductive characters to compare the newly found ciliate with typical C. irritans. The newly found ciliate had an additional process in the reproductive stage, characterized by a budding before palintomic division, and it showed a higher ability to carry out tomitogenesis at a low temperature (16 degrees C) than at a high temperature (24 degrees C). Nevertheless, the present ciliates still had much in common with typical C. irritans with respect to clinical, histopathological, and morphological characters, suggesting that it is a new strain of C. irritans, adapted to lower water temperature. PMID- 11206737 TI - Neoparamoeba Page, 1987: light and electron microscopic observations on six strains of different origin. AB - Although amoebic gill disease (AGD) has emerged as one of the most severe health problems in the fish industry, proof of the identity of AGD agents from various localities is still missing. Six strains of amoebae designated until recently as Paramoeba species (the agents of AGD) were studied in cultures by light and electron microscopy. Although they were isolated from gills of different hosts (Dicentrarchus labrax and Scophthalmus maximus) and from distant localities, their morphology was identical. The strains differed from Paramoeba eilhardi, the type species of the genus, in that they lacked the boat-shaped microscales on the cell surface but could be safely identified as belonging to the genus Neoparamoeba Page, 1987. Transmission electron microscopy revealed the presence of a symbiotic organism, Perkinsiella amoebae Hollande, 1980, in all strains under study. The only difference among the strains examined was found in the size of trophozoites, which could be attributed to the different origins of the strains, but until more refined diagnostic methods are available, in addition to N. pemaquidensis, the closely related species N. aestuarina also has to be taken into consideration as the agent of AGD. PMID- 11206738 TI - Ultrastructural justification for the transfer of Pleistophora anguillarum Hoshina, 1959 to the genus Heterosporis Schubert, 1969. AB - This study presents the ultrastructure of the microsporidian infecting the trunk musculature of Anguilla japonica and originally described as Pleistophora anguillarum Hoshina, 1959. All stages develop within a special structure, the sporophorocyst (SPC), which is equipped with a thick dense wall. This wall grows along with the growth of the parasites within it. Meronts are uni- to binucleate, which divide and steadily give rise to sporonts. During transition to sporonts the cell coat of the meronts increases its thickness, temporarily featuring thick irregular projections. Eventually a uniformly thick sporont wall is formed, then the sporont cells detach themselves from the wall (= future wall of the sporophorous vesicle, SPV) and start a series of divisions to produce sporoblasts. The SPV wall is compact, has no pores and consists of 2 layers. The presence of the SPC justifies the transfer of the species into the genus Heterosporis. Spores from disrupted SPCs are ingested by macrophages and within them are spread into various body tissues including the outermost layers of the epidermis. From here, they can easily be released to the outside and can contaminate the environment while the host is still alive. PMID- 11206739 TI - A new shell disease in the mud crab Scylla serrata from Port Curtis, Queensland (Australia). AB - In 1994 a previously unreported rust spot shell disease was seen in mud crabs Scylla serrata - Forskal from Port Curtis, central Queensland, Australia. Of 673 crabs surveyed, 21.7% had shell lesions. Of these, 82.9% had rust spot lesions on the carapace. The majority of rust spot-affected crabs (78.8%) were female. Rust spot lesions were predominantly non-perforated (89.4%) and 54.8% were bilaterally symmetrical. There was also a gender difference in the areas of the carapace most commonly affected. The main histological features of the rust spot lesion included: a cavity in the upper endocuticle; indentation of the endocuticle below the cavity; remains of muscle attachment adhesive epithelium within the cavity; fibrous connective tissue between the damaged carapace and the attached muscle; and islands of endocuticle in this fibrous connective tissue. Histopathology of the internal organs failed to find evidence of an infectious or parasitic cause of the rust spot lesions. The cause(s) of the syndrome appear(s) to be non infectious. PMID- 11206740 TI - Transcaruncular approach to medial canthal tendon plication for lower eyelid laxity. AB - PURPOSE: A new operation to correct lower eyelid laxity was evaluated. METHODS: A new transcaruncular, orbital approach to posterior medial canthal tendon plication was performed on eight orbits of four cadavers, which were then analyzed with computed tomography or histologic techniques. The procedure was also performed on 23 eyelids of 15 patients with lower eyelid medial canthal tendon laxity, alone or in conjunction with other procedures. These patients were followed up for a mean of 12 months. RESULTS: Improved postoperative eyelid position, epiphora, and superficial punctate keratopathy were found. Radiographic and histologic analysis demonstrated consistency of suture placement without involvement of contiguous anatomical structures. CONCLUSIONS: This procedure appears to be a safe, reproducible, and effective corrective procedure for medial canthal tendon laxity and lagophthalmos. When combined with lateral lower eyelid tightening, it is also an effective treatment for lower eyelid retraction and superficial punctate keratopathy. Other potential advantages and complications of this procedure are described in comparison to other reported surgical methods used to address medial canthal tendon laxity and malpositions of the medial lower eyelid. PMID- 11206741 TI - Stabilization of the posterior limb of the medial canthal tendon using biodegradable tag anchors: a cadaveric model. AB - PURPOSE: This study describes and tests in a cadaveric model a new method of fixation designed for potential stabilization of the posterior limb of the medial canthal tendon, using biodegradable Tag anchors. METHODS: Study of the possibility of performing surgery to repair medial ectropion using biodegradable polyglyconate Tag anchors was commenced in the sheep cadaveric head model, and in the whole dry human skull model. This was then performed using five preserved human cadaveric whole heads, and pullout tensions were estimated in four of these. Computed tomography and magnetic resonance imaging were obtained for this model in the fifth head, and computed tomography was performed on the whole dry human skull. Dissections were carried out to establish the site of the bony defect in each of the heads. RESULTS: It was possible to obtain good Tag anchor fixation in bone overlying the maxillary and ethmoidal sinuses of the sheep, and in a young human skull. It was also possible to place adequately the anchor in the medial wall of the orbit close to the posterior lacrimal crest in all cases in the human cadaveric model. Pullout strengths were evaluated and found to range from 3.5 N to 12.4 N (mean, 7.5 N). Computed tomography and magnetic resonance imaging failed to demonstrate the biodegradable anchors in both the dry human whole skull and in the fifth cadaveric head, but did demonstrate the bony defects in the medial orbital walls through which the anchor passed. CONCLUSIONS: We have shown, for the first time, the stability of biodegradable Tag anchor fixation in a human cadaveric head model using pullout tensions and dissection studies. This method would allow adequate strength and stability to provide for control of fixation of the medial end of the lower eyelid in patients with medial ectropion and medial canthal tendon laxity. PMID- 11206742 TI - Flap minimization via peripheral recruitment. AB - PURPOSE: To describe tissue-conserving modifications to traditional flap design such as the use of beveled incisions and the pattern of the incisions. These techniques should maintain flap viability and enhance cosmesis. METHODS: We describe the techniques of peripheral flap recruitment. RESULTS: Flaps conformed to reduced geometry, beveled incisions and bases, and tapered ends maximize vascularity. Peripheral tissues are recruited to fill primary defects; smaller flaps thus can be used to fill larger defects. Additionally, this flap design enhances cosmetic results and maintains a high probability for flap survival. CONCLUSION: The described novel flap design has many potential advantages over traditional designs. Correctly applied, these flap techniques spare tissue, decrease scarification, trauma and bleeding, and reduce the need for secondary procedures. Potential drawbacks of this flap design include temporary anatomic distortion especially over rounded structures such as the nose. Complications are minimal. PMID- 11206743 TI - Aesthetic surgery: diagnosing and healing the miscues of human facial expression. PMID- 11206744 TI - Evisceration with scleral modification. AB - PURPOSE: To describe an evisceration technique that combines scleral modification with optic nerve release for coverage of any sized orbital implant. METHODS: The medical records of 70 patients who underwent the described evisceration procedure were reviewed. RESULTS: The average implant was 20 mm in diameter, with 50 patients (71%) receiving a solid polymethylmethacrylate sphere. Fifty-eight patients (83%) had a history of at least one previous ocular surgery, and 12 patients (17%) had phthisical eyes preoperatively with moderate to severe scleral cicatrization. Postoperatively, there were two cases of new or worsened ptosis, no cases of worsened motility, and no cases of implant extrusion. CONCLUSION: Evisceration with scleral modification is a simple and effective procedure that allows placement of any size orbital implant. Surgical results are excellent with few complications. PMID- 11206745 TI - Chronic dacryocystitis in American mucocutaneous leishmaniasis. AB - PURPOSE: This study describes lacrimal tract involvement and surgical outcome in patients with mucocutaneous leishmaniasis. METHODS: Four patients, ages 20 to 75 years, had nasal lesions resulting from mucocutaneous leishmaniasis and sought treatment for chronic dacryocystitis. Each patient had had lacrimal symptoms since childhood or early adulthood, concomitantly with the development of upper airway lesions. Dacryocystography showed nasolacrimal duct stenosis in all cases on the affected side. Three patients underwent dacryocystorhinostomy (one bilaterally), and one patient had bilateral dacryocystectomy. RESULTS: Two patients had surgical fistula closure soon after surgery. A sequential endoscopic operation for remotion of a synechia between the fistula and the middle turbinate was successful in one of these patients. Histopathologic analysis of lacrimal sacs and nasal mucous membranes close to the anastomotic site revealed chronic nonspecific inflammatory process and negative immunohistochemistry for Leishmania. CONCLUSIONS: Dacryocystitis may result from nasal mucocutaneous leishmaniasis. The surgical outcome was unsatisfactory in one of the four patients. PMID- 11206746 TI - A case of bilateral cryptophthalmia and euryblepharon with two-stage reconstruction. AB - PURPOSE: A two-stage reconstruction of cryptophthalmia and euryblepharon occurring in the same patient is described. METHODS: Case report. RESULTS: The 7 month-old patient underwent forniceal reconstruction and upper eyelid reformation in a two-stage procedure that used the excess lower eyelid tissue present in euryblepharon to augment the cryptophthalmia-related upper eyelid deficiency. CONCLUSIONS: To reconstruct the eyelids of this patient with both cryptophthalmia and euryblepharon, we were able to use the manifestations of one disorder to address the deficiencies of the other. PMID- 11206747 TI - Congenitally anomalous tented eyebrows. AB - PURPOSE: An uncommon congenital anomaly of the eyebrows is described. METHODS: Case report and review of the literature. RESULTS: Two articles in the English literature were found describing patients similar to ours. CONCLUSIONS: Congenital upward tenting of the midportion of the eyebrows, resembling the eyebrow line of an owl, is uncommon. This anomaly is thought to be transmitted in an autosomal dominant fashion and may be accompanied by myopia and strabismus, but has not been associated with systemic disease. PMID- 11206748 TI - Orbital malignant fibrous histiocytoma following irradiation for retinoblastoma. AB - PURPOSE: An unusual case is reported of orbital malignant fibrous histiocytoma that developed after irradiation for retinoblastoma. METHODS: Case report. RESULTS: A 5-month-old girl underwent enucleation of the left eye, external beam irradiation of the right eye, and systemic chemotherapy for bilateral sporadic retinoblastoma. At age 17 years, a malignant fibrous histiocytoma developed in the medial aspect of the orbit and nasal cavity. After attempted excisional biopsy, she underwent craniofacial resection, orbital exenteration, maxillectomy, and tracheostomy. The patient was alive 12 months postoperatively without local or metastatic disease. CONCLUSIONS: Although orbital fibrous histiocytoma occurs usually as a primary tumor of adulthood, it can also develop as a secondary tumor after irradiation for retinoblastoma. PMID- 11206749 TI - Successful treatment of rhino-orbital mucormycosis without exenteration: the use of multiple treatment modalities. AB - PURPOSE: To describe the successful management of rhino-orbital mucormycosis without the use of orbital exenteration. METHOD: Case report. RESULTS: The patient had successful eradication of the fungal infection with retention of normal vision and ocular function. CONCLUSIONS: The use of multiple treatment modalities including aggressive surgical debridement guided by intraoperative frozen section monitoring, intravenous liposomal amphotericin B, intraorbital regular amphotericin B and hyperbaric oxygen may allow complete resolution of orbital phycomycosis and spare the patient from the blindness and disfigurement associated with exenteration. PMID- 11206750 TI - Intraorbital rupture of a cavernous internal carotid artery aneurysm: therapeutic options. AB - PURPOSE: To describe the use of an endovascular therapeutic technique in the management of a giant carotid cavernous aneurysm. METHODS: We reviewed the clinical and neuroradiologic findings of a patient with an unusual case of carotid cavernous aneurysm and intraorbital rupture. The medical literature was searched for similar cases and to review the use of endovascular techniques. RESULTS: The patient was treated by balloon occlusion of the left internal carotid artery. CONCLUSIONS: Endovascular techniques can be used to treat complex giant cranioorbital cavernous aneurysms. PMID- 11206751 TI - Five things oculoplastic surgeons should know about medical genetics. PMID- 11206752 TI - Sudoriferous cyst of the orbit. AB - PURPOSE: A case of sudoriferous cyst of the orbit in an adult patient is reported. This unusual cyst in the orbit has heretofore been reported only in congenital cases. METHODS: Case report. RESULTS: A 45-year-old woman sought treatment for an asymptomatic mass of the left lower eyelid. Computed tomography of the orbits showed a cystic lesion in the inferior orbit with bony remodeling. Histopathologic examination showed the lesion to be a solitary cyst lined by two to three layers of cuboidal epithelial cells with eosinophilic cytoplasm. Some of the epithelial cells contained periodic acid-Schiff-positive, diastase-resistant granules. The pathologic diagnosis was a sudoriferous cyst. CONCLUSION: Sudoriferous cysts, although uncommon, should be included in the differential diagnosis of orbital cystic tumors. PMID- 11206753 TI - Suggested precautions when using a monocanalicular stent. PMID- 11206754 TI - Stress analysis of the aortic valve with and without the sinuses of valsalva. AB - BACKGROUND AND AIM OF THE STUDY: In some patients with dilated aortic root, attempts have been made to replace the aorta and preserve the anatomically normal leaflets. The tubular Dacron graft used in the valve-sparing procedure does not have the sinuses of Valsalva, and therefore might adversely affect the valve. The effect of the presence or absence of the sinuses was investigated on stresses in the leaflets. METHODS: Finite element models of the tubular aortic root and the root with the sinuses were constructed. The model dimensions were: aorta radius 13 mm; valve height 18 mm; leaflet thickness 0.5 mm; aorta and sinus wall thickness 1.3 mm. In the root with the sinuses, each leaflet-sinus unit formed a cylindrical geometry. The model was loaded with an internal pressure of 80 mmHg (0.01 N/mm2) and the stress determined. RESULTS: The stress in the leaflet belly was 0.26 N/mm2, and not affected by the geometry and stiffness of the root. In the tubular root there was a stress concentration along the leaflet attachment, and the stress reached 0.65 N/mm2; in contrast, in the sinus root there was no stress concentration and maximum stress was only 0.3 N/mm2. Under pressure, the leaflet-sinus assembly expanded in a uniform manner, whereas in a tubular root large deformations occurred along the leaflet attachment. CONCLUSION: The sinuses of Valsalva play a very important role in minimizing stress in the leaflets; thus, use of the sinus graft is expected to enhance the longevity of the spared valve. PMID- 11206755 TI - Hemodynamic assessment of the Medtronic Mosaic bioprosthesis in the aortic position. AB - BACKGROUND AND AIM OF THE STUDY: The Medtronic Mosaic bioprosthesis (MMB) is a newly developed tissue valve which incorporates several features such as a low profile semi-flexible stent, zero-pressure tissue fixation, and anti mineralization pretreatment with alpha-amino oleic acid aimed to improve hemodynamics and prevent structural deterioration. METHODS: Between November 1995 to June 1999, 62 patients underwent aortic valve replacement (AVR) with the MMB; 41 of these who reached the one-year follow up interval and who had isolated AVR without any concomitant procedure with size 23 mm and 25 mm MMB were evaluated by serial echocardiography after three, six and 12 months. RESULTS: For size 23 mm valves, mean and peak gradients were 12+/-3 and 21+/-6 mmHg at 3 months, 12+/-3 and 20+/-5 mmHg at 6 months, and 12+/-4 and 20+/-6 mmHg at 12 months. For size 25 mm valves, mean and peak gradients were 13+/-2 and 22+/-4 mmHg at 3 months, 12+/ 3 and 21+/-5 mmHg at 6 months, and 12+/-4 and 22+/-6 mmHg at 12 months. In patients with 23 mm MMB, left ventricular mass index (LVMi) was reduced from 181+/-34 g/m2 before surgery to 158+/-32, 150+/-28 and 140+/-25 g/m2 at 3, 6 and 12 months after AVR (p <0.001); in patients with 25 mm MMB, LVMi was reduced from 182+/-28 g/m2 before surgery to 165+/-25, 156+/-24 and 146+/-19 g/m2 at 3, 6 and 12 months after AVR (p <0.001). CONCLUSION: Our results indicate that MMB is associated with low mean and peak gradients and significant reduction in LVMi throughout the postoperative period. Thus, the MMB appears to be an excellent cardiac valve substitute in elderly subjects who require AVR. PMID- 11206756 TI - A new design for polyurethane heart valves. AB - BACKGROUND AND AIM OF THE STUDY: The synthetic flexible tri-leaflet heart valve offers considerable potential for improvement in both hydrodynamic and biomechanical performance of replacement heart valves. To date, success with the synthetic leaflet heart valve has been limited, partly due to limitations in the biostability of the polyurethanes used. With the synthesis of new biostable polyurethanes, the integration of advancing technology, and better knowledge of the functional and biomechanical design requirements necessary to increase the long-term durability of the polyurethane heart valve, novel clinical solutions are now in sight. METHODS: This study describes the design characteristics, hydrodynamic and biomechanical performance of a new design of polyurethane heart valve. The function and durability characteristics of this novel design of heart valve, manufactured using a proven durable non-biostable polyurethane, was compared with that of a single AorTech porcine bioprosthetic heart valve and a single tilting disc mechanical heart valve, the Bjork-Shiley Monostrut valve (BSM), of similar size. RESULTS: For equivalent sizes of valve, the new polyurethane heart valve design had significantly lower pressure gradients compared with the porcine valve at all flow rates and to the BSM valve at the higher flow rates. The effective orifice area of the polyurethane valve was greater than the other two valves studied; regurgitation and total energy loss were less. The new polyurethane valve design reached over 360 million cycles in an accelerated durability tester, without failure. CONCLUSION: This new design of polyurethane heart valve showed improved hydrodynamic function in comparison with either the porcine bioprosthetic or the BSM mechanical heart valve. The pulsatile flow results showed a lower total energy loss associated with this valve, indicating improved potential patient benefit. The durability of this new design of polyurethane heart valve was demonstrated when manufactured using a medical grade polyurethane. PMID- 11206758 TI - Aortic insufficiency after surgical repair of acute type a aortic dissection: incidence, indications for reoperation and medical management. AB - Recurrent aortic insufficiency presents in as many as 20% of patients late after repair of acute type A aortic dissection. This underscores the need for life-long follow up and appropriate management of patients after such surgery. The prevalence of, and risk factors for, recurrent aortic regurgitation, and the indications for and results of medical and surgical treatment are discussed. PMID- 11206757 TI - Harvested porcine mitral xenograft fixation: impact on fluid dynamic performance. AB - BACKGROUND AND AIM OF THE STUDY: Recent developments suggest that stentless bioprosthetic mitral valve heterografts should be considered in order to optimize valve hydrodynamics. The fixation process alters the mechanical properties of tissue. This study investigates the changes in mitral valve morphology and hemodynamic performance following fixation. METHODS: Porcine mitral valves were excised and attached to a physiological annular ring. Mitral valve function was studied in vitro with a rigid transparent left heart model, allowing transverse and sagittal views. Initial experiments were performed with fresh valves under physiological conditions. Three different papillary muscle positions were used, and each was recorded. After glutaraldehyde fixation, genipin fixation, and cryopreservation, the valves were re-studied while maintaining cardiac output. Performance characteristics before and after fixation were obtained from hydrodynamic pressure and flow data, high-speed video camera, digital video, Doppler ultrasound, and three-dimensional papillary muscle force measurements. Morphology changes were detected by detailed anatomic measurements of the valves before and after fixation. RESULTS: Valve length was reduced by 18.5% after fixation with genipin (p <0.001), but not with glutaraldehyde. Cryopreserved valves showed no statistically significant changes in morphology or hydrodynamic performance after preservation. The forward flow opening area was reduced by 12.2% (p <0.001) after glutaraldehyde fixation, and by 32.3% (p = 0.004) after genipin fixation. Thus, maximal forward flow velocity was increased by 33.3% (p = 0.008) after glutaraldehyde fixation and by 52.8% (p = 0.001) after genipin fixation. The flow acceleration was consistent with a funnel shape of the fixed valves causing important flow contraction beyond the orifice (vena contracta). The papillary muscle force increased with apically posterior papillary muscle displacement by 20.4% (p = 0.001) and 101.5% (p <0.001) after glutaraldehyde and genipin fixation, respectively, and total regurgitant volume was increased by 91.6% (p <0.001) and 117.3% (p <0.001), respectively. The work required by the heart simulator to maintain a constant cardiac output at constant vascular resistance increased by 24.2% (p = 0.003) and 34.2% (p = 0.004) after glutaraldehyde and genipin fixation, respectively. CONCLUSION: The present study shows that chemical fixation of porcine mitral valves adversely affects the hemodynamics of the valves, increasing overall workload. The effects were more severe after fixation with genipin than with glutaraldehyde. This suggests the need to explore other fixation agents to optimize valvular cardiac function. Cryopreservation had no detrimental effects on valvular hemodynamic performance. PMID- 11206759 TI - Structural modification and cryopreservation of porcine heart valves for xenotransplantation with reduced immunity. AB - BACKGROUND AND AIM OF THE STUDY: In order to provide valved xenografts with reduced immunity, yet durability comparable with that of homografts, a method for endothelial cell removal was developed. METHODS: Adult porcine valved pulmonary conduits were isolated, washed and incubated in trypsin-EDTA solution. The endothelial cells were flushed free with a stream of culture medium, and the xenografts cryopreserved. Grafts were thawed after three months, and evaluated structurally. RESULTS: Macroscopic inspection of the grafts revealed no cracks or other morphological damage. Light microscopy revealed mildly edematous changes, and the elastic layers appeared to be preserved. Incubation with trypsin-EDTA solution consistently removed the entire endothelial layer, without obvious damage to the underlying tissues. CONCLUSION: With care and appropriate timing, the xenograft endothelium can be selectively removed, leaving the underlying tissue intact. This process may allow further structural manipulations to improve the durability of these grafts. PMID- 11206760 TI - Diagnostic value of intraoperative swabs of heart valves in infective endocarditis. AB - BACKGROUND AND AIM OF THE STUDY: Intraoperative swabs of heart valves are obtained regularly from patients undergoing heart valve surgery for infective endocarditis (IE) in order to confirm the preoperative diagnosis and to adjust the antibiotic regimen. The study aim was to assess the diagnostic value of intraoperative swabs of heart valves in IE. METHODS: A total of 83 patients was referred for surgical treatment of active IE between October 1994 and May 1999. Preoperatively, microorganisms were isolated using a minimum of two positive blood cultures; results were compared with those obtained from intraoperative heart valve swab cultures. RESULTS: Preoperatively, 73 patients (88%) had a positive blood culture, and 10 (12%) had culture-negative endocarditis. The intraoperative swab confirmed the preoperative diagnosis in 31 cases (37%). Bacteria were isolated in three of the ten patients with preoperative culture negative IE. Despite positive histopathological findings in seven patients, no microorganisms were cultured either pre- or intraoperatively. Among the remaining 42 patients (51%) with active IE, 25 valve cultures were sterile and 17 valve swabs were presumed to be contaminated. CONCLUSION: In patients with active IE in whom the causative agent could be isolated and identified before surgery, intraoperative valve swabs did not contribute further to patient management. In isolating contaminants, the risk of inappropriate modification of the antibiotic regimen is imminent. The diagnostic validity in culture-negative IE appears negligible. PMID- 11206761 TI - Fractured occluder disc: a previously unrecognized complication of the Starr Edwards disc prosthesis. AB - Fracture of the occluder disc of a low-profile Starr-Edwards prosthesis is a hitherto unrecognized complication. We describe a patient who presented with right heart failure and severe pulmonary hypertension 27 years after mitral valve replacement with a model 6520 caged-disc prosthesis. At surgery, there was a longitudinal split in the occluder disc, and organized thrombus was lodged between the split segments. This case offers a unique opportunity to study the long-term effects of wear on the polyethylene poppet and Stellite cage. PMID- 11206762 TI - Long-term pathological changes of expanded polytetrafluoroethylene (ePTFE) suture in the human heart. AB - Expanded PTFE (ePTFE) sutures have been used widely as a mitral chordal substitute. We present a structural analysis of ePTFE sutures implanted as artificial chordae for 7.5 years and 8.6 years in patients with mitral regurgitation. No calcification was found either macroscopically or microscopically, and the ePTFE suture retained its normal flexibility. The suture was totally encapsulated with host tissues composed of dense fibrous tissue covered with endothelial cells. PMID- 11206763 TI - Comparison of cardiovascular risk and lipid profiles in patients undergoing aortic valve surgery versus those undergoing coronary artery bypass grafting. AB - BACKGROUND AND AIM OF THE STUDY: Hyperlipidemia is a risk factor for the progression of coronary artery disease, and possibly also valvular aortic stenosis. Thus, patients with aortic stenosis, coronary disease (or both) might be expected to have more abnormal lipid profiles than those without these two conditions. METHODS: The lipid profiles of patient subsets undergoing aortic valve replacement (AVR) with or without concomitant coronary artery bypass grafting (CABG), as well as those undergoing isolated CABG, between 1987 and 1997 were analyzed retrospectively. Four surgical groups were identified: AVR for aortic regurgitation (n = 370); AVR for predominant aortic stenosis (n = 1,072); AVR for aortic stenosis (AS) with CABG (n = 914); and isolated CABG (n = 11,156). The complete fasting lipid profiles of patients were collected, analyzed by group, and compared. RESULTS: Analysis by Spearman's correlation showed that total cholesterol levels, triglycerides and low-density lipoproteins (LDL-C) were modestly, yet significantly, increased in each successive group, while high density lipoproteins were decreased. AS patients undergoing isolated AVR had significantly higher total cholesterol (215 versus 201 mg/dl; p <0.0001), triglycerides (125 versus 104 mg/dl; p <0.0001) and LDL-C (139 versus 132 mg/dl; p = 0.003) than those undergoing AVR for aortic regurgitation. Total cholesterol >200 mg/dl was significantly associated with AS, even after adjusting for differences in age, sex, diabetes mellitus and hypertension, with an odds ratio of 1.5 (95% confidence interval, 1.2-2.0; p = 0.001). CONCLUSION: Progressively abnormal lipid profiles are associated with AS and coronary disease in patients undergoing AVR. This evidence helps to extend the link between dyslipidemia and AS in a large consecutive series of patients. PMID- 11206764 TI - Aortic surgery in patients with marfan syndrome: long-term survival, morbidity and function. AB - BACKGROUND AND AIM OF THE STUDY: The natural history of patients with Marfan syndrome is depressing, but surgical intervention on the aorta can improve the prognosis. Study results were analyzed with reference to long-term survival, morbidity and function. METHODS: Seventy-four Marfan patients (51 males, 23 females; mean age 41+/-14 years), underwent first-time aortic surgery between 1977 and 1998. Follow up information regarding mortality, morbidity and functional status was obtained from patient records and by questionnaire. The mean follow up was 5 years (range: 0-19 years). Forty-seven patients (64%) had a dissection, 27 (36%) an aneurysm, and 45 (61%) patients underwent emergency operations (<4 h from arrival at hospital). In 72 patients (97%) the disease affected the ascending aorta, and implantation of a composite graft was the most frequent operation. RESULTS: Overall 30-day mortality was 12% (3% in elective cases, 18% in emergency cases, p <0.05). Emergency operations and surgery extended to the aortic arch were risk factors for early mortality. Overall actuarial survival was 63.4+/-8% at 10 years. Age was the only risk factor for late mortality. Seventeen patients were reoperated on due to pathologies of the remaining aorta (n = 12), pseudoaneurysms (n = 4) and aortic valve endocarditis (n = 1). A total of five patients had endocarditis; one patient with a homograft required surgery, and medical treatment was successful in the other four patients. Five patients had neurological thromboembolic episodes without permanent damage, and six had minor bleeding complications. Freedom from early and late mortality, reoperation on the aorta and major cardiovascular events (endocarditis episodes, thromboembolic/hemorrhagic strokes and other major bleeding/embolic episodes) was 33.3 +/- 8.1% at 10 years. At follow up, 98% of patients were in NYHA functional class I or II, and 80% were working. CONCLUSION: Elective aortic surgery in Marfan patients can be performed with good results. Close follow up of patients undergoing surgery is important. The long-term functional status of surviving patients is satisfactory. PMID- 11206765 TI - Influence of transesophageal echocardiography on intraoperative decision making for toronto stentless prosthetic valve implantation. AB - BACKGROUND AND AIM OF THE STUDY: Intraoperative transesophageal echocardiography (TEE) is commonly used during aortic valve surgery. In aortic valve replacement (AVR), this permits measurement of the aortic annulus, study of the anatomy of aortic valve components, and prediction of prosthesis valve size. After cardiopulmonary bypass (CPB), echocardiography is valuable in checking prosthesis function. In this study, we evaluated the impact of intraoperative TEE on the decision-making process of aortic Toronto stentless prosthetic valve (TSPV) implantation. METHODS: Fifty-two consecutive patients undergoing elective AVR were collected prospectively. Multiplane TEE was performed before CPB to determine diameters of the aortic valve annulus and sinotubular junction. This was to evaluate the feasibility of TSPV implantation in the aortic position and to predict prosthesis size. Further TEE evaluation was carried out after CPB to assess prosthetic valve function. RESULTS: TEE allowed measurement of the aortic annulus and sinotubular junction, and enabled correct prediction of prosthesis size. Ultrasonic evaluation also revealed contraindications to TSPV implantation in five patients. In one case, color-Doppler examination led to immediate successful surgical correction of prosthetic incompetence. CONCLUSION: Intraoperative multiplane TEE examination is useful in the decision-making process in AVR with the TSPV by selecting patients suitable for the stentless valve, predicting prosthesis size, and checking prosthesis function. PMID- 11206766 TI - Medium-term follow up of pulmonary autograft aortic valve replacement: technical advances and echocardiographic follow up. AB - BACKGROUND AND AIM OF THE STUDY: The Ross procedure (aortic valve replacement (AVR) with pulmonary autograft and pulmonary homograft replacement of pulmonary valve) was developed as a durable aortic valve substitute that avoids the need for anticoagulation and provides young patients with a long-lasting aortic valve substitute. Our seven-year follow up echocardiography data are reviewed. METHODS: Between May 1993 and March 2000, 40 adult patients (28 males, 12 females; mean age 33.3 years) underwent the Ross procedure at the Brigham and Women's Hospital for congenital aortic stenosis (n = 6), aortic insufficiency (n = 17) and mixed disease (n = 17). All patients had aortic root replacement with the pulmonary autograft and had no regurgitation after operation. Postoperative evaluation was conducted by transthoracic echocardiography, office visit and/or telephone interview. NYHA functional class, aortic and pulmonary valve function and aortic root dimensions were evaluated. RESULTS: One patient died postoperatively as a result of a low output state related to global left ventricular dysfunction. Four patients (10%) developed pulmonary homograft stenosis with a peak gradient >40mmHg; and six developed mild pulmonary stenosis. One patient had aortic insufficiency seven years postoperatively that required valve replacement. Eight patients developed mild dilatation (>37 mm) of the neoaortic root, and five of these had aortic insufficiency. One patient required transplantation at 40 months for restrictive cardiomyopathy. CONCLUSION: The Ross procedure is an effective means of AVR that can be accomplished with low perioperative morbidity and mortality if certain technical modifications are carried out. In this series of 40 patients with mid-term follow up, a significant number developed moderate pulmonary trunk stenosis, though echo characterization demonstrated good valve function. PMID- 11206767 TI - Left ventricular remodeling after pulmonary autograft replacement of the aortic valve (Ross operation). AB - BACKGROUND AND AIM OF THE STUDY: Aortic valve replacement (AVR) with a pulmonary autograft is an alternative treatment for young patients with aortic valve disease. Superior hemodynamic performance of the pulmonary autograft, and impact on parameters of left ventricular function were analyzed. METHODS: Thirty patients (21 males, nine females; mean age 29.97+/-12.29 years; range: 6-54 years) underwent a Ross procedure between November 1997 and November 1999. Seven patients (23%) were children (aged <15 years). In total, 22 patients were analyzed; each had at least three months follow up. Eleven patients had predominant aortic stenosis (AS), and 11 had aortic insufficiency (AI). RESULTS: There were no operative deaths. Two patients developed severe insufficiency, and the autograft was replaced with a mechanical valve. Pre- and postoperative echocardiograms were reviewed. The mean neoaortic maximal gradient was 7.85+/ 5.59 mmHg (range: 3-29 mmHg). AS patients showed reduced interventricular septal (IVS) thickness at one month (from 13.27+/-3.69 to 11.60+/-2.44 mm; p = 0.0165) and 18 months after surgery (p = 0.0104). Left ventricular posterior wall (LVPW) thickness was reduced from 12.04+/-3.75 to 9.48+/-2.47 mm (p = 0.0338) at one month and 18 months (p= 0.0128) after surgery. The left ventricular end-diastolic internal dimension (LVIDd) decreased from 50.71+/-10.20 to 44.98+/-7.29 mm (p = 0.0491) at one month after surgery. In AI patients, LVPW and IVS thicknesses showed no significant variation, and LVIDd was decreased at one month (from 68.50+/-8.39 to 59.04+/-9.21 mm; p = 0.0017) and 18 months (p = 0.0229) after surgery. Left ventricular end-systolic internal dimension (LVIDs) decreased from 44.06+/-6.39 to 39.03+/-7.99 mm (p = 0.0081) at three months after surgery. Left ventricular mass index (LVMI) in the AS group decreased from 179.01+/-62.26 to 115.74+/-37.62 g/m2 (p = 0.0021) at one month after surgery, and at 18 months was normal, with a decrease from 208.77+/-32.89 to 95.89+/-28.82 g/m2 (p= 0.0003) (n = 5). In the AI group, LVMI decreased from 186.25+/-85.21 to 140.58+/-62.02 g/m2 (p = 0.0011) at one month after surgery, and at 18 months from 217.70+/-98.02 to 146.73+/-84.55 g/m2 (p= 0.0131) (n = 5). CONCLUSION: The pulmonary autograft procedure can be used safely to replace the aortic valve, and allows optimal hemodynamic performance, with no significant aortic regurgitation. The Ross procedure results in normalization of left ventricular dimensions and improvement of left ventricular function early in the postoperative period. PMID- 11206769 TI - Relationship between papillary muscle size and benefit to cardiac function in mitral valve replacement with chordal preservation. AB - BACKGROUND AND AIM OF THE STUDY: Mitral valve replacement (MVR) with chordal preservation in patients with chronic mitral regurgitation (MR) has been reported to maintain systolic function of the left ventricle. However, the benefits of MVR with chordal preservation are not always predictable. The study aim was to ascertain the influence that papillary muscle (PM) size has on cardiac function after MVR with chordal preservation. METHODS: Postoperative regional shortening and its relationship with PM size were investigated by two-dimensional echocardiography in 18 patients who underwent MVR with chordal preservation, and nine patients without chordal preservation between 1986 and 1998 at Tenri Hospital. The PM cross-sectional area was measured in each patient, as well as postoperative fractional shortening (FS) of the septolateral, anteroposterior and vertical dimensions of the left ventricle. The technique of preserving all chordae tendineae involved reattaching the anterior leaflet chordae to the mitral annulus near each commissure. RESULTS: Postoperative FS of the septolateral and anteroposterior dimensions was better in patients with chordal preservation than in those without. In the former subgroup, a larger PM was associated with better FS of the left ventricle in the septolateral dimension (anterior PM, p <0.001, r = 0.78; posterior PM, p = 0.0010, r = 0.69), but not in the anteroposterior or vertical dimensions. This discrepancy in the relationship between PM size and functional benefits among the three dimensions may be related to the direction in which the PMs are suspended in our technique, or its effect on regional left ventricular function. CONCLUSION: The present study indicated that PM size may be used as a factor to better predict the outcome of MVR with chordal preservation. PMID- 11206768 TI - Effect of cardiac output on mitral valve area in patients with mitral stenosis: validation and pitfalls of the pressure half-time method. AB - BACKGROUND AND AIM OF THE STUDY: The non-invasive evaluation of mitral valve area is often used in the assessment of patients with mitral stenosis. The pressure half-time method is commonly used to calculate valve area, but is inaccurate in many clinical scenarios. We sought to quantify the effects of changing cardiac output on the accuracy of mitral valve area determination. METHODS: Thirteen patients with mitral stenosis underwent routine stress echocardiography with resting and peak exercise results compared. A previously described and clinically validated mathematical model of the cardiovascular system was used to validate the clinical results. Seven different loading conditions for each of four different stenotic valve areas were modeled. RESULTS: In patients, with increasing cardiac output, pressure half-time decreased (-30.6+/-35.3 ms/l/min) and calculated valve area increased by 0.25+/-0.30 cm2/l/min. By continuity, it appeared that approximately half of this increase was due to actual valve orifice stretching, the remainder reflecting fundamental changes in the relationship between half-time and valve area. Mathematical modeling resulted in similar changes in pressure half-time and calculated valve area (0.06 to 0.12 cm2/l/min, p = 0.20 versus clinical results). CONCLUSION: Changes in cardiac output result in predictable changes in pressure half-time, and should be considered when performing serial examinations in patients with mitral stenosis. PMID- 11206770 TI - Transesophageal echocardiography as predictor of mitral valve repair. AB - BACKGROUND AND AIM OF THE STUDY: Mitral valve repair has recently emerged as the treatment of choice in patients presenting with insufficiency due to valve prolapse. The study aims were to evaluate: (i) the clinical presentation in a consecutive series of patients with mitral valve prolapse undergoing surgical repair; (ii) the correlation between pre- and intraoperative echocardiographic features and surgical findings in these patients; and (iii) whether clinical and echocardiographic data may predict surgical outcome. METHODS: Between March 1997 and May 2000, 152 patients (110 men, 42 women; mean age 59+/-13 years) were recruited into the study. All patients had myxomatous mitral valve disease causing severe regurgitation and underwent systematic examination by transesophageal echocardiography (TEE) for clear delineation of the three scallops of the posterior leaflet and juxtaposed segments of the anterior leaflet. RESULTS: In 119 patients (78%) a flail valve was documented by TEE and confirmed on surgical inspection; an anterior leaflet chordal rupture was not visualized by TEE in one case. In 15 cases (10%) there was flail of the anterior leaflet, and in 105 cases (69%) flail of the posterior leaflet. A bileaflet complex prolapse without chordal rupture was found in 32 cases. On the basis of TEE evaluation, mitral valve replacement was performed electively in 10 patients (7%); the other 142 (93%) underwent mitral valve repair. Adequate repair was obtained in 93% of cases; residual mitral regurgitation (eight cases; grade 3+) and mitral stenosis (one case) were documented by intraoperative TEE, and nine patients (6%) underwent valve replacement. CONCLUSION: The majority of patients with myxomatous mitral valve prolapse and severe regurgitation undergoing valve repair have chordal rupture of the posterior mitral leaflet, a condition in which results of valve repair are excellent. TEE provides a powerful means to define the mechanisms of mitral regurgitation and to identify the suitability of patients for valvuloplasty. PMID- 11206771 TI - Mitral valve repair and transesophageal echocardiographic findings in a high-risk subgroup of patients with active, acute infective endocarditis. AB - BACKGROUND AND AIM OF THE STUDY: Limited data are available regarding the efficacy of mitral valve repair in patients affected by active, acute infective endocarditis. In addition, the predictivity of transesophageal echocardiography (TEE) for guiding the surgical decision-making process in these patients has not yet been reported. The study aim was to evaluate the long-term results of mitral valve repair and role of TEE in active, acute infective endocarditis. METHODS: The study population consisted of patients affected by infective endocarditis of the mitral valve who underwent surgery. TEE was performed intraoperatively to guide the best surgical approach. All patients were followed up (mean 73+/-8 months) after surgery. RESULTS: Twenty-eight patients underwent surgery for infective endocarditis; of these, 13 had mitral valve repair for active, acute infective endocarditis and formed the basis of the study. Sensitivity, specificity, positive predictive value, negative predictive value of TEE in detecting the mechanism of mitral regurgitation were 87%, 100%, 100% and 92%, respectively. The predictivity test of TEE in guiding surgical strategy was 94%. All patients were alive at the time of follow up; 10 (77%) were in NYHA class I and three in class II (23%). Mitral regurgitation was severe in one patient (8%), moderate in three (23%), mild in four (31%), and absent in five (38%). No relapses of active infective endocarditis were observed during the follow up period. CONCLUSION: Mitral valve repair appears to be an effective treatment for active, acute infective endocarditis with mitral regurgitation and should be considered as a therapeutic strategy when surgery is contemplated. TEE has a fundamental role in the surgical decision-making process in these patients. PMID- 11206772 TI - Mechanical versus biological valve prosthesis in the mitral position: a 10-year follow up of St. Jude Medical and Biocor valves. AB - BACKGROUND AND AIM OF THE STUDY: During the past 30 years, the development of mechanical and biological valves has led to major improvements in patient survival. Here, we present long-term results obtained with both types of prosthesis. METHODS: At our institution, between 1985 and 1989, 158 patients received a Biocor porcine bioprosthesis, and 100 patients a St. Jude Medical (SJM) mechanical valve. Preoperatively, mean age, male:female ratio, NYHA functional class and pathology of mitral valve disease were similar in both groups. RESULTS: The 30-day mortality was 4.4% in the Biocor group and 4% in the SJM group, the major cause being congestive heart failure. Late mortality was 17.9% and 15.6% respectively in the two groups, but valve-related mortality was very low in both (1.3% versus 4.2%). Ten-year survival was similar in each group (77.8+/-3.4% versus 81.0+/-3.9%; p = 0.538). Ten-year freedom from anticoagulant related hemorrhage was higher with Biocor prostheses (99.3+/-0.7% versus 90.9+/ 3.1%; p = 0.007). Valve thrombosis was seen only in the SJM group, and structural valve degeneration (SVD) only in the Biocor group. Ten-year freedom from reoperation was lower in the Biocor group (84.9+/-3.2% versus 92.2+/-2.8%; p = 0.206). The significant causes of reoperation were SVD in the Biocor group and valve thrombosis in the SJM group. Freedom from prosthetic valve endocarditis was similar in both groups (96.3+/-1.6% versus 95.5+/-2.2%). CONCLUSION: As no difference was seen in survival and reoperation rates between patients receiving either bioprostheses or mechanical valves, the valve used will depend on the surgeon's choice and the type of patient, notably elderly patients who are intolerant of anticoagulation, and young women wishing to have children. PMID- 11206773 TI - Mitral valve replacement with chordal preservation in a rheumatic population. AB - BACKGROUND AND AIM OF THE STUDY: Mitral valve replacement (MVR) with preservation of the subvalvular apparatus may maintain postoperative left ventricular (LV) function better than conventional MVR. A prospective study was undertaken to assess the advantages of chordal preservation in rheumatic patients undergoing isolated MVR. METHODS: Between January 1996 and January 1999, 240 patients with rheumatic etiology and normal LV ejection fraction (>50%) underwent isolated MVR using a St. Jude Medical prosthesis. Patients were allocated to two groups: in group I (n = 168), both the anterior and posterior chordae were preserved; in group II (n = 72), the entire native mitral valve apparatus was excised. Patients from both groups were evaluated postoperatively (mean 12.5 months) by echocardiography and treadmill testing. RESULTS: Demographic and clinical profiles were comparable in both groups. There were three early deaths in group I, and one in group II. There were no late deaths. One patient in group I required reoperation for a stuck mitral prosthesis. LV function (ejection fraction >50%) was better in group I (94%) than in group II (82%) (p <0.05). No patient in either group had LV outflow tract obstruction on echocardiography. Patients in group I showed better exercise performance on treadmill (Bruce protocol): 92% of group I patients versus 88% of group II patients (p >0.05) completed stage I; 16% of group I patients, but no group II patients, were able to complete stage IV (p <0.05). CONCLUSION: Mitral valve replacement with preservation of the subvalvular apparatus maintains LV function, and does not cause LV outflow tract obstruction. PMID- 11206774 TI - Case report: outer sheath rupture may precede complete chordal rupture in fibrotic mitral valve disease. AB - Rupture mechanics of mitral valve chordae have been difficult to elucidate because most surgical repairs and pathological examinations are performed after the rupture. In an excised anterior leaflet from a fibrotic mitral valve, chordae were observed in an initial phase of rupture. Microscopic sections showed that thinned, nearly ruptured chordal segments were actually chordal cores, containing highly aligned collagen fibers. The outer sheath of elastic fibers, disorganized circumferentially oriented collagen fibers, and endothelial cells that normally surrounds the collagen core apparently had retracted to the extreme ends of the thinned segment, resulting in a bulbous shape, as noted in the chordal rupture literature. In conclusion, these new observations lead us to propose that the rupture of mitral valve chordae is not spontaneous, but may occur over time. The failure of the outer sheath may represent the first phase in a slow, two-part process leading to eventual chordal rupture. PMID- 11206775 TI - Early clinical experience with the On-X prosthetic heart valve. AB - BACKGROUND AND AIM OF THE STUDY: The study was designed to investigate the clinical performance of the On-X prosthetic heart valve in a multicenter experience. METHODS: Between September 1996 and September 1999, 301 patients (56% males) underwent isolated On-X valve replacement (184 isolated aortic (AVR), 117 isolated mitral (MVR)) at 11 European centers under a standardized protocol. Average age at implant was 60.2 years. Office or hospital follow up was required by the protocol; average follow up on all patients was 11 months. RESULTS: Thirty day mortality in the study was 2.2% for AVR and 6.0% for MVR, with valve-related mortality of 0.5% for AVR. There were eight late deaths (0.7%/pt-yr AVR and 2.3%/pt-yr MVR). Two of these deaths were sudden, and thus possibly valve-related (one AVR, one MVR). Early total valve-related morbidity was 3.5% for AVR and 2.6% for MVR. In total, 13 thromboembolic events occurred; one early event in AVR resulted in death (0.5%), and one transient early event occurred in MVR (0.9%). There were 11 late events (seven AVR (1.7%/pt-yr) and four MVR (1.8%/pt-yr)), for a two-year freedom from thromboembolism of 96.6% after AVR and 97.1% after MVR. Three late bleeding events occurred, all after AVR (0.7%/pt-yr and 98.9% free at two years). Major paravalvular leaks requiring reoperation occurred on two occasions early (one AVR (0.5%), one MVR (0.8%)) and once late in MVR (0.5%/pt yr). Late minor, untreated paravalvular leaks occurred in three AVR patients (0.7%/pt-yr) and in one MVR patient (0.5%/pt-yr). Prosthetic endocarditis occurred four times (two AVR (0.5%/pt-yr), two MVR (0.9%/pt-yr)), all within the first 12 months of surgery. Actuarial freedom from all valve-related events at two years was 88.7% for AVR and 88.1% for MVR. NYHA class was improved in 75.8% of AVR patients and 70.6% of MVR patients at two years after surgery. CONCLUSION: These early results indicate that the On-X valve provides satisfactory clinical outcome in the immediate postoperative period, and that the valve is both safe and effective. PMID- 11206776 TI - High-performance liquid chromatographic enantiomeric separation of an enzyme inhibitor which possesses both a chiral center and tautomeric moieties. AB - The enantiomeric separation using high-performance liquid chromatography (HPLC) on chiral stationary phases (CSPs) of a chiral compound which exists in solution in several tautomeric forms is described. 2,4-Dioxo-5-acetamido-6-phenylhexanoic acid is the most potent inhibitor known for peptidylamidoglycolate lyase (PGL, EC 4.3.2.5), an enzyme which plays an essential role in carboxyl-terminal amidation of many biological peptides. Synthesis of this inhibitor entails an alkaline hydrolysis step, under which condition the compound is racemized; thus, HPLC with a CSP was employed to obtain the individual enantiomers of this inhibitor. Since 2,4-dioxo-5-acetamido-6-phenylhexanoic acid exists in solution in several tautomeric forms, the strategy of first converting this compound from its multiple enol forms into a single diketo tautomer, which was then applied to various CSPs, was employed. Successful preparative scale enantiomeric separation of this compound was achieved using a Chiralpak AD CSP. Enantiomeric separation was also accomplished on a D-penicillamine column, but this CSP was found to be less satisfactory for preparative purposes. PMID- 11206777 TI - Optical resolution of asymmetric triacylglycerols by chiral-phase high performance liquid chromatography. AB - A simple method for direct optical resolution of some asymmetric triacylglycerols (TGs) has been established. The method employs chiral-phase high-performance liquid chromatography (HPLC). An enantiomeric pair of TGs comprising 1 eicosapentaenoyl-2,3-dicapryroyl-sn-glycerol (ECC) and 1,2-dicapryroyl-3 eicosapentaenoyl-sn-glycerol (CCE) was resolved on a CHIRALCEL OF or on a CHIRALCEL OD column. The separation of another pair of asymmetric TGs, 1 docosahexaenoyl-2,3-dicapryroyl-sn-glycerol (DCC) and 1,2-dicapryroyl-3 docosahexaenoyl-sn-glycerol (CCD), was achieved with the CHIRALCEL OD column. The chiral-phase HPLC method in combination with silver-ion HPLC and high-temperature gas chromatography was used for monitoring two interesterification reactions, whose products were chiral TGs. Interesterification of tricapryloylglycerol with ethyleicosapentaenoate or with ethyldocosahexaenoate was performed using Rhizomucor miehei lipase as the catalyst. The products targeted were the asymmetric pair of TGs, ECC and CCE or DCC and CCD. The amounts of sn-1 substituted products (ECC or DCC) were greater than their sn-3-substituted counterparts (CCE or CCD) throughout the reaction period, suggesting that R. miehei lipase had a stereopreference towards the sn-1 position over the sn-3 position. PMID- 11206778 TI - Reversed-phase high-performance liquid chromatographic separation of tert.-butyl hydroperoxide oxidation products of unsaturated triacylglycerols. AB - Triacylglycerols containing monounsaturated fatty acids are known to be relatively resistant to autoxidation and require long periods of exposure to dilute oxidants. Use of concentrated solutions of synthetic hydroperoxides, however, yields in addition to the hydroperoxides also unidentified oxidation by products. In the present study we have employed synthetic triacylglycerols containing one (18:0/18:1/18:0 and 18:1/16:0/16:0) and two (18:0/18:0/18:2 and 18:1/18:1/18:0) double bonds per molecule to reinvestigate the formation of oxotriacylglycerols using tert.-butyl hydroperoxide as an oxidant. Reversed-phase HPLC was used to separate and tentatively identify the oxidation products based on relative retention times of standards and the estimated elution factors for functional groups and their positional distribution. Hydroperoxides, diepoxides and hydroxides were the major components of the oxidation mixtures (50-95% of total). Previously unidentified peroxide-bridged tert.-butyl adducts were present in significant amounts (5-50% of total oxidation products) in all preparations. In several instances more than one functional group was present on a single fatty chain. The tentative reversed-phase chromatographic identification of the adducts was confirmed by determination of the molecular mass of each component by on-line LC with electrospray MS. The oxidation products were quantified by HPLC with light scattering detection. PMID- 11206779 TI - Bi-column method for purification of transcription factors. AB - A novel bi-column method for purifying transcription factors, using two different columns and two different elution strategies is described. Lac repressor elutes at lower heparin concentrations from a lower affinity lactose operatorl (Op1) Sepharose column than from a higher affinity column containing the same sequence with a T18:A18 tail (Op1T18). A bi-column method was developed in which lac repressor fusion protein is eluted from the Op1-Sepharose with a low heparin concentration and trapped on a Op1T18-Sepharose column because of its higher affinity for the lac repressor protein. Elution of the latter column with buffer containing a high salt concentration gives significantly purer transcription factor than the conventionally used single column methods and removes residual heparin. Highly pure CAAT enhancer binding protein and the B3 transcription factor are also obtained by using variants of this bi-column method. PMID- 11206780 TI - Determination of porphyrins and metalloporphyrins using liquid chromatography diode array detection and mass spectrometry. AB - A HPLC procedure has been optimized and successfully applied to porphyrins of environmental interest, such as etio and octaethylporphyrins and their VO and Ni compounds. The use of UV-Vis diode array allowed the detection of the analytes within the 5-15 ng/ml range. In order to achieve greater specificity and some structural information, the coupling of liquid chromatography with mass spectrometry was investigated, and the particle beam interface conditions were optimized. Electron impact (EI) spectra, comparable to those reported in the literature were obtained. The entire procedure has been applied to a real marine sediment, previously spiked with porphyrins to resemble oil-contaminated samples. The results pointed out that the method is suitable for such levels of analytes (5-10 microg/ml), allowing their identification and quantification with no need for purification steps. PMID- 11206781 TI - Preparative isolation and purification of lutein from the microalga chlorella vulgaris by high-speed counter-current chromatography. AB - High-speed counter-current chromatography (HSCCC) was applied to the isolation and purification of lutein from microalgae. Analytical HSCCC was used for the preliminary selection of a suitable solvent system composed of n-hexane-ethanol water (4:3:1, v/v). Using the above solvent system, preparative HSCCC was successfully performed yielding lutein at 98% purity from 200 mg of the crude extract in a one-step separation. PMID- 11206782 TI - Determination of metal complexes of ethylenediaminetetraacetate in the presence of organic matter by high-performance liquid chromatography. AB - A high-performance liquid chromatography method is described here for the determination of the Cd(II), Co(II), Cu(II), Pb(II), and Zn(II) complexes of ethylenediaminetetraacetate (EDTA) in municipal wastewaters and surface waters. The method involves separation by ion-exchange chromatography on a reversed-phase C18 column coated with ion-pair reagent, followed by post-column conversion to FeEDTA and subsequent detection by UV absorbance. Although Co(II) and Cu(II) coelute, they can be quantified by analyzing absorbance by CuEDTA2- prior to post column conversion. The method detection limit of 6-8 x 10(-8) M (5-7 ng) is an order of magnitude improvement over previous UV absorbance post-column reaction methods. The technique can be used in the presence of organic matter encountered in matrices such as untreated wastewater without pre-concentration or sample cleanup. PMID- 11206783 TI - TiO2 colloidal suspension polydispersity analysed with sedimentation field flow fractionation and electron microscopy. AB - Sedimentation field flow fractionation (SdFFF) operated at multi gravitational field is used to analyse a highly polydisperse TiO2 colloidal suspension. From the initial sample, time dependent eluted fractions are collected and submitted to electron microscopy (EM) shape and size analysis. To assess the accuracy of FFF in determining the average size of the different fractions, these are re introduced into the channel by means of two different procedures, the on-channel concentration of the fractions and the direct re-injection of pre-concentrated fractions (DRI). Both methods appear accurate to determine the average size of every fraction, associated to a lower recovery in the case of DRI. The fractogram band spreading characteristics of the re-introduced fractions are correlated to the particle size distribution measured by EM. After density determination of fractionated particles, the fractogram is calibrated in terms of size and size distribution using data obtained from EM for each fraction. Quantitative analyses, based on particle counting showed high recovery (80-90%) of the eluted species. However, this loss limited the possibility to extend signal information to a quantitative one. PMID- 11206784 TI - Semi-preparative gas chromatographic separation of all-trans-perhydrotriphenylene enantiomers on a chiral cyclodextrin stationary phase. AB - Enantiomers of all-trans-perhydrotriphenylene (PHTP) were separated by gas chromatography using heptakis(6-O-tert.-butyldimethylsilyl-2,3-di-O-methyl)-beta cyclodextrin (TBDMS-beta-CD) as the chiral selector. Conditions for semi preparative separations were established using a 2 m x 2 mm I.D. packed column and subsequently extended to a 1.8 m x 4 mm I.D. column which enabled separations on a mg scale. The column packing was TBDMS-beta-CD dissolved in SE-54 coated on Chromosorb P AW-DMCS 80-100 mesh. Optimization of the chromatographic conditions (oven temperature, carrier gas flow, and column load) with respect to better efficiency and peak retention resulted in a system capable of separating up to 10 mg of the racemate per day. Purities of separated enantiomers were determined by capillary gas chromatography. Yields and purities of the fractions obtained by single- and double-step separations are compared. Highly enriched enantiomers with purities of up to 99.6% (99.2% ee) were obtained by a single separation step. PMID- 11206785 TI - Comparison of direct and indirect methods of measuring the precursors of beta methyl-gamma-octalactone and their application to the analysis of Sessile oak wood. AB - A new indirect method for measuring the level of beta-methyl-gamma-octalactone precursors in oak wood by GC-MS is described. This level is calculated from the difference between the amount of free beta-methyl-gamma-octalactone and the amount formed after hydrolysis and lactonization. It is compared to the level of a precursor of cis-beta-methyl-gamma-octalactone, a 6'-O-gallate derivative of (3S,4S)-4-[3-beta-glucopyranosyloxy-3-methyloctanoic acid, determined directly by HPLC. These two methods are applied to 12 powdered samples of Sessile oak wood and the results show that the 6'-O-gallate derivative of (3S,4S)-4-beta-D glucopyranosyloxy-3-methyloctanoic acid is by far the most abundant precursor of beta-methyl-gamma-octalactone in this wood. PMID- 11206786 TI - Nuclear magnetic resonance studies of solvent flow through chromatographic columns: effect of packing density on flow patterns. AB - NMR (nuclear magnetic resonance) techniques have been used to measure and characterise solvent flow through chromatographic columns. NMR imaging was used to track an injection of D2O. PGSE (pulsed gradient spin echo) NMR was used to measure the flow-rate dependence of axial and transverse apparent diffusion. A combination of these two techniques (dynamic NMR imaging) gave the spatial distribution of the local velocity and apparent diffusion through a cross-section of the column. Significant column wall effects were observed and these effects were found to be highly dependent upon the column packing density. The column performance was assessed in terms of the HETP (height equivalent to a theoretical plate) determined by the NMR techniques employed. PMID- 11206787 TI - Gas chromatography-mass spectrometry and chemometric resolution applied to the determination of essential oils in Cortex cinnamomi. AB - In this paper, a novel procedure for qualitative and quantitative analysis of the two-dimensional data obtained from GC-MS is investigated to determine chemical components of essential oils in Cortex Cinnamomi from four different producing areas. A new method named iterative optimization procedure (IOP) specially used to resolve embedded peaks is also developed. With the help of IOP and other chemometric techniques, such as heuristic evolving latent projections, evolving factor analysis, sub-window factor analysis and orthogonal projection resolution, and etc., the detection of the purity of chromatographic peaks can be first addressed, and then the overlapping peaks are resolved into the pure chromatogram and mass spectrum of each component. The similarity searches in the MS database are finally conducted to qualitatively determine the chemical components. The results obtained showed that the accuracy of qualitative and quantitative analysis could be greatly enhanced by chemometric resolution methods. The chemometric resolution techniques upon the two-dimensional data can be quite promising tools for the analysis of the complex samples like traditional Chinese medicine. PMID- 11206788 TI - Structural determination of zinc dithiophosphates in lubricating oils by gas chromatography-mass spectrometry with electron impact and electron-capture negative ion chemical ionization. AB - Pentafluorobenzyl ester derivatives were used to identify zinc dialkyldithiophosphates and diaryldithiophosphates antiwear engine oil additives by GC-electron impact ionization (EI) MS and GC-electron-capture negative ion chemical ionization (ECNCI) MS analysis. GC-EI-MS of the dialkyldithiophosphate pentafluorobenzyl derivatives afforded characteristic fragment ions corresponding to the cleavage of one and two alkyl radicals. In most cases, information was only obtained on one alkyl chain. Additional and complete information was obtained with retention time indices using synthetic derivatives and with GC ECNCI-MS analysis. ECNCI afforded characteristic dithiophosphate anions which allowed the determination of the total number of carbon atoms in the alkyl radicals. The diastereoisomer mixtures of 2-hydroxy-sec.-alkyl radicals were completely separated on GC analysis. PMID- 11206789 TI - Multiresidual method for the gas chromatographic analysis of pesticides in honeybees cleaned by gel permeation chromatography. AB - The analysis of several organophosphorus and carbamate pesticide residues in the bodies of honeybees using gas chromatography (GC) and gel permeation chromatography (GPC) clean-up is described. Freeze-dried or lyophilized insect samples were blended with diatomaceous earth (Extrelut) then underwent elution with methylene chloride. This extraction method has shown good recovery on various spike standard levels. Samples are cleaned up by GPC with a Bio Beads SX 3 column and a cyclohexane-ethylacetate (1:1) eluant. Organophosphorus and carbamate compounds are quantified using capillary gas chromatography. Good linearity ranges were observed for all compounds. The extraction process was rapid and results were good, despite the complexity of the matrix on which it was applied. It allowed a reduction both in cost and the consumption of solvents, thereby safeguarding the health of the analyst and the environment. Environmental monitoring using bees was confirmed to be a valid procedure. PMID- 11206790 TI - Two-fibre solid-phase microextraction combined with gas chromatography-mass spectrometry for the analysis of volatile aroma compounds in cooked pork. AB - The volatile aroma compounds in cooked pork were examined using solid-phase microextraction (SPME). Two SPME fibres coated with different stationary phases were used simultaneously to collect aroma compounds from the headspace above the pork. One fibre was coated with 75 microm. Carboxen-polydimethylsiloxane and the other was coated with 50/30 microm divinylbenzene-Carboxen on polydimethylsiloxane. After extraction, the two fibres were desorbed in the injection port of a gas chromatograph sequentially, so that the aroma compounds from both of the fibres could be analysed in one gas chromatogram. This procedure resulted in a chromatogram containing a more complete aroma profile for cooked pork than the chromatograms from either of the fibres on their own. Thirty-six compounds were identified in cooked pork for the first PMID- 11206791 TI - High-throughput reactor for simulating the flame photometric detector. AB - Quenching of luminescing species by co-eluting hydrocarbons has been widely reported in the flame photometric detector (FPD). This paper describes a novel method of investigating the chemical behavior of both analyte and quencher molecules in the FPD. The method is designed to reproduce the FPD's behaviour on a large scale by using a custom-built reactor. The high-throughput reactor's multi-capillary burner, situated inside a glass housing, is well suited to approximate the low-temperature, fuel-rich conditions of the conventional FPD, and also allows the study of various other flame phenomena. Wide regions of gas composition can be accessed by both diffusion- and premixed-type flames, and products can be easily sampled. Effluent collection demonstrates that 2 to 82% of various organic compounds may survive passage through the diffusion flame and be recovered intact. The recovery of several (unchanged) model hydrocarbons was found to decrease with increasing carbon number. Hetero-atoms such as sulfur, nitrogen, or oxygen greatly decrease the recovery of molecules relative to their pure hydrocarbon analogues. Compared to a diffusion flame, the recoveries of n alkanes from a premixed flame are much lower and largely independent of carbon number or volatility. PMID- 11206792 TI - Chain separation of monounsaturated fatty acid methyl esters by argentation thin layer chromatography. AB - A technique for separating methyl esters of monounsaturated fatty acids by argentation chromatography using silver nitrate-impregnated TLC plates is described. Monounsaturated fatty acid methyl esters are separated from polyunsaturated and saturated fatty acid methyl esters and the monounsaturated fatty methyl esters are resolved according to chain length. cis isomers are well resolved from the corresponding trans isomers. R(F) values for individual monounsaturated fatty acids are very reproducible. The potential of the technique in metabolic studies is demonstrated in the chain elongation of [14C]-18:1(n-9) and delta-9 desaturation of [14C]-18:0 by human skin fibroblasts. Recoveries of individual [14C]-fatty acids for scintillation counting exceed 94%. PMID- 11206793 TI - Capillary zone electrophoresis of basic analytes in methanol as non-aqueous solvent mobility and ionisation constant. AB - The electrophoretically relevant properties of monoacidic 21 bases (including common drugs) containing aliphatic or aromatic amino groups were determined in methanol as solvent. These properties are the actual mobilities (that of the fully ionised weak bases), and their pKa values. Actual mobilities were measured in acidic methanolic solutions containing perchloric acid. The ionisation constants of the amines were derived from the dependence of the ionic mobilities on the pH of the background electrolyte solution. The pH scale in methanol was established from acids with known conventional pK*a values in this solvent used as buffers, avoiding thus further adjustment with a pH sensitive electrode that might bias the scale. Actual mobilities in methanol were found larger than in water, and do not correlate well with the solvent's viscosity. The pK*a values of the cation acids, HB-, the corresponding form of the base, B, are higher in methanol, whereas a less pronounced shift was found than for neutral acids of type HA. The mean increase (compared to pure aqueous solution) for aliphatic ammonium type analytes is 1.8, for substituted anilinium 1.1, and for aromatic ammonium from pyridinium type 0.5 units. The interpretation of this shift was undertaken with the concept of the medium effect on the particles involved in the acid-base equilibrium: the proton, the molecular base, B, and the cation HB+. PMID- 11206794 TI - Optimization of background electrolytes for capillary electrophoresis I. Mathematical and computational model. AB - A mathematical and computational model is introduced for optimization of background electrolyte systems for capillary zone electrophoresis of anions. The model takes into account mono- or di- or trivalent ions and allows also for modeling of highly acidic or alkaline electrolytes, where a presence of hydrogen and hydroxide ions is significant. At maximum, the electrolyte can contain two co anions and two counter-cations. The mathematical relations of the model are formulated to enable an easy algorithmization and programming in a computer language. The model assesses the composition of the background electrolyte in the analyte zone, which enables prediction of the parameters of the system that are experimentally available, like the transfer ratio, which is a measure of the sensitivity in the indirect photometric detection or the molar conductivity detection response, which expresses the sensitivity of the conductivity detection. Furthermore, the model also enables the evaluation of a tendency of the analyte to undergo electromigration dispersion and allows the optimization of the composition of the background electrolyte to reach a good sensitivity of detection while still having the dispersion properties in the acceptable range. Although the model presented is aimed towards the separation of anions, it can be straightforwardly rearranged to serve for simulation of electromigration of cationic analytes. The suitability of the model is checked by inspecting the behavior of a phosphate buffer for analysis of anions. It is shown that parameters of the phosphate buffer when used at neutral and alkaline pH values possess singularities that indicate a possible occurrence of system peaks. Moreover, if the mobility of any analyte of the sample is close to the mobilities of the system peaks, the indirect detector signals following the background electrolyte properties will be heavily amplified and distorted. When a specific detector sensitive on presence of the analyte were used, the signal would be almost lost due to the excessive dispersion of the peak. PMID- 11206795 TI - Sulfonated acrylamide copolymers as pseudo-stationary phases in electrokinetic chromatography. AB - Sulfonated copolymers were synthesized, characterized and used as separation media in electrokinetic chromatography. The polymers used were synthesized from AMPS (2-acrylamido-2-methyl-1-propanesulfonic acid) and LMAm (lauryl methacrylamide) in different mole ratios (from 100:0 to 60:40). Electrophoretic mobilities and methylene selectivities were calculated, which showed the expected correlation with the monomer ratios. The chemical selectivities for the separation of nine solutes by the copolymers were compared with that of sodium lauryl sulfate micelles, showing significant differences. No significant difference in chemical selectivities was observed for copolymers with different monomer ratios. No significant change of hydrophobic microdomain of copolymers was found in background buffers with different ionic strength values, based on the investigation of the retention factors, methylene selectivities and polymer effective mobilities. No change of hydrophobic microdomain of the copolymer solutions was found at copolymer concentrations from 0.17 to 3% (w/v), however, plots of k' versus polymer concentration suggested a different copolymer phase at lower concentrations (from 0 to 0.1%, w/v) from that at higher concentrations (from 0.17 to 3%, w/v). The copolymer with AMPS-LMAm (80:20) could be chosen as optimum copolymer as far as the methylene selectivity, peak symmetry and polymer mobility were concerned. PMID- 11206796 TI - Polyacrylamides as hydrophilic selectors in non-aqueous capillary electrophoresis. AB - Polyacrylamides (PAAms) were investigated as hydrophilic selectors in non-aqueous capillary electrophoresis (CE). Separation of 10 substituted benzoates and unsubstituted benzoate as model samples was greatly improved by the addition of PAAms in acetonitrile-CE. The migration behavior indicates that the carbonyl moiety of PAAms works as a good hydrogen-accepting site toward hydrogen-donating analytes such as 4-hydroxybenzoate anion (4OH-BA) in acetonitrile. PAAms also serve as electron-accepting agents with its amide proton interacting with the dissociated carboxyl groups of the benzoates. The ion-dipole interaction is useful to control the migration behavior of benzoates without hydrogen-donating substituents. The overall mode of the interaction is similar to that of polyethylene glycol (PEG) 20000 reported previously, but the complex formation constant of poly(N-tert.-butyl)acrylamide (PBAAm) with 40H-BA estimated here was 130-fold larger than that of PEG 20000. This would be ascribed to the strong basicity of the carbonyl oxygen atoms of PBAAm as compared with the ether oxygen atoms of PEG. Furthermore, a copolymer of (N-tert.-butyl)acrylamide-acrylamide [70:30 (in feed)] exhibited a complex formation constant of about fourfold larger toward 4OH-BA than PBAAm, most probably due to decrease in steric hindrance from the tert.-butyl groups. Adrenaline and its six precursors have been separated successfully using the PAAms. PMID- 11206797 TI - Characterization of polyethylene glycol-modified proteins by semi-aqueous capillary electrophoresis. AB - A new program to characterize polyethylene glycol-modified (PEGylated) proteins is outlined using capillary zone electrophoresis (CZE). PEGylated ribonuclease A and lysozyme were selected as examples. Five separation procedures were compared to select out the mixed buffer of acetonitrile-water (1:1, v/v) at pH 2.5 as the best to characterize the PEGylated proteins without sample pretreatment. Polyethylene oxide (PEO) with a high molecular mass of 8 x 10(6) was applied to rinse the capillary to form a dynamic coating which would decrease the undesirable proteins adsorbed to the inner wall of the silica. The electroosmotic flow (EOF) mobility of the five procedures was determined, respectively. It is found that acetonitrile is mainly responsible for the good resolution of PEGylated proteins with the help of PEO coating in the semi-aqueous system. The low EOF mobility and current in the semi-aqueous system might also have some responsibility for the high resolution. The semi-aqueous procedure described in this paper also demonstrates higher resolution of natural proteins than aqueous ones. PMID- 11206798 TI - Influence of the solute hydrophobicity on the enantioselective adsorption of beta blockers on a cellulase protein used as the chiral selector. AB - Adsorption isotherm data were acquired at different eluent pH values for the enantiomers of several beta-blockers on cellobiohydrolase I on silica gel. They fit well to the biLangmuir model, allowing the determination of the equilibrium constants and the monolayer capacities for chiral and nonselective adsorption. The adsorption of the S-enantiomers (eluted second) is exothermic at low pH, endothermic at high pH, and athermal in a narrow pH range depending on the beta blocker. This transition pH range is lower for S-alprenolol than for the more hydrophobic S-propranolol, although their endothermic adsorption originates from hydrophobic interactions. This surprising observation is explained by the relative values of the isotherm coefficients. S-Alprenolol seems to have a more pronounced endothermic behavior than S-propranolol because the nonselective interactions of both compounds with the stationary phase are exothermic but their contribution to retention, relative to that of the endothermic chiral interactions, is less important for alprenolol. The order of increasing energy of the chiral interactions is the same as that of hydrophobicity, propranolol>alprenolol>metoprolol. PMID- 11206800 TI - Separation of the insecticidal pyrethrin esters by capillary electrochromatography. AB - A simple, rapid technique for the direct separation and quantification of the six insecticidally active pyrethrin esters in typical extracts and commercial formulations by capillary electrochromatography (CEC) has been described. The separation of the pyrethrin esters was achieved by optimizing several parameters including the length of stationary phase, the mobile phase composition and column temperature. The mobile phase composition had the most pronounced effect toward resolving these structurally similar compounds. A ternary mobile phase composed of acetonitrile-aqueous buffer-tetrahydrofuran (55:35:10) provided the elutropic solvent strength needed to resolve the six esters from an extract mixture in under 16 min. A 25 cm packed bed of Hypersil 3 microm C18 stationary phase was used with the ternary mobile phase at 25 degrees C and 30 kV voltage. These conditions also yielded excellent separation of the pyrethrin esters in two different commercially available insecticidal formulations. In addition, the developed CEC method was shown to be a fast and easy way of quantifying the amount of these esters in typical pyrethrin formulations. PMID- 11206799 TI - Applications of a copper microparticle-modified carbon fiber microdisk array electrode for the simultaneous determination of aminoglycoside antibiotics by capillary electrophoresis. AB - A copper microparticle-modified carbon fiber microdisk array electrode was fabricated and employed in capillary electrophoresis for the simultaneous determination of the five aminoglycoside antibiotics (AGs) including netilmicin, tobramycin, lincomycin, kanamycin and amikacin. The array electrode exhibited high catalytic activity for AGs, good reproducibility and stability. Under the optimum separation conditions (separation voltage of 6.2 kV, electrophoretic medium of 125 mM NaOH), the five AGs above were baseline separated within 20 min. At a working electrode potential of 0.7 V (versus saturated calomel electrode), the calibration curves were linear over two orders of magnitude of concentration, and the detection limits (SIN=3) were below 2 microM except for lincomycin (6.7 microM). The developed method was successfully employed for the simultaneous determination of the five AGs studied in pharmaceutical injections. The feasibility of this method for the simultaneous determination of lincomycin, kanamycin and amikacin in urine sample was also demonstrated. PMID- 11206801 TI - Chiral ion-pair chromatography on porous graphitized carbon using N-blocked dipeptides as counter ions. AB - Two newly synthesized chiral di-anionic counter ions were tested for enantiomeric resolution of a set of amino alcohols on porous graphitized carbon, Hypercarb. Z L-Aspartyl-L-proline dissolved in methanol baseline resolved nine of 12 tested racemates. One of its diastereoisomers, Z-L-aspartyl-D-proline was also tested but resulted in low separation factors, <1.1. Sodium hydroxide was added to the mobile phase in order to titrate the counter ion to its mono- or di-anionic form. Results show that the di-anionic form was found to be superior to the mono anionic form regarding enantioselectivity. Increased content of the counter ion in the mobile phase, with constant ratio between counter ion and sodium hydroxide concentration, decreased retention but only slightly affected enantioselectivity. Increased retention and enantioselectivity were observed with decreased column temperature. Resolution factors >3 were obtained between the enantiomers in atenolol and metoprolol with a total retention time of less than 15 min. Further, all four stereoisomers of an analogue to metoprolol were separated using Hypercarb and a mobile phase of 5 mM Z-L-aspartyl-L-proline and 9 mM sodium hydroxide in methanol. PMID- 11206802 TI - Application of reinforced frontal affinity chromatography and advanced processing procedure to the study of the binding property of a Caenorhabditis elegans galectin. AB - Frontal affinity chromatography is a very useful and simple method to analyze molecular interactions between an analyte and an immobilized ligand by calculating the extent of "retardation" of the elution front. We developed a very simple and efficient data-processing procedure that enables the measurement of very small differences in retardation with precision. This procedure was successfully applied to comparison of the binding properties of recombinant C. elegans galectins for their ligand. PMID- 11206803 TI - Determination of retinoids in galenicals by column liquid chromatography with fluorescence and diode-array detection. AB - Simple and rapid reversed-phase gradient column liquid chromatography (LC) with fluorescence detection at different wavelengths was developed for the simultaneous analysis of all-trans, 13-cis, 9-cis retinoic acids, vitamin A palmitate and beta-carotene in galenicals. The assay results agreed with those obtained by an LC method with diode-array UV detection. A post-column on-line photochemical reactor (irradiation at 254 and 366 nm) was inserted between the LC column and the fluorescence detector to enhance the performance of the method. Two fluorescence spectra (photoreactor on and off) were obtained for each analyte which proved useful for the unambiguous identification of the various analytes. PMID- 11206804 TI - Evaluation of the retention dependence on the physicochemical properties of solutes in reversed-phase liquid chromatographic linear gradient elution based on linear solvation energy relationships. AB - This paper describes the results of the evaluation of retention dependence on the physicochemical properties of solutes in linear gradient elution by reversed phase liquid chromatography (RPLC) based on linear solvation energy relationships (LSERs). Retention time data on Inertsil ODS(3) column by linear gradient elution were collected for both acetonitrile-water and methanol-water binary mobile phases under various gradient steepness. Based on the LSERs, the retention times were linearly correlated with the physicochemical properties (size, dipolarity, and hydrogen bond donor-acceptor acidity and basicity) of solutes. As predicted by LSERs, very acceptable linear relationships are observed for both mobile phases. While the magnitudes of the coefficients are modified by the gradient steepness, their signs are consistent with those obtained by isocratic elution. As obtained for isocratic elution, the dominant factors to retention in linear gradient elution of RPLC are the solutes' size and hydrogen bond acceptor basicity. The conclusions of the study allow us to predict retention in chromatographic method development by gradient elution. PMID- 11206805 TI - Effect of pH on the oxidation of paralytic shellfish poisoning toxins for analysis by liquid chromatography. AB - The effect of pH on the oxidation of individual PSP toxins using both periodate and peroxide oxidations was studied. It was found that the optimum pH for individual toxins varied considerably. For periodate oxidations, pH 8.2 produced the maximum yield of fluorescent products for neosaxitoxin and GTX1/GTX4 while the non-hydroxylated toxins (saxitoxin, GTX2/GTX3, decarbamoyl saxitoxin, GTX5) showed optimum pHs from about pH 10-11.5. Neosaxitoxin and GTX1/GTX4 did not produce significant fluorescent oxidation products with peroxide oxidation at any of the pHs studied (pH 8.2-12.8). The non-hydroxylated toxins all showed optimum pHs above pH 12 with peroxide oxidation. Yields of fluorescent products of these toxins decreased substantially at pHs below pH 12. Neosaxitoxin and GTX1/GTX4 each produced three product peaks at pH 8.2 with periodate oxidation. There was no pH where these toxins produced predominantly a single oxidation product. Decarbamoyl saxitoxin always produced two oxidation products with both oxidation reactions at the pHs studied. However, the relative yields of the products changed with pH. At low pH the second eluting product predominated, while at higher pH values the first eluting product predominated. This pattern was observed for both oxidation reactions. The other non-hydroxylated toxins produced mainly single unique products with both oxidation reactions over the pH range studied. No single pH was found optimum for the oxidation of both hydroxylated and non-hydroxylated toxins without a significant compromise in yield of oxidation products. This has implications for the post column oxidation liquid chromatographic methods, since small changes in pH of the post column oxidant can both positively and negatively affect the yields of oxidation products of toxin mixtures leading to increased error in the subsequent quantitation of these compounds. PMID- 11206806 TI - Characterisation of sorbate geometrical isomers. AB - trans,trans Isomers of sorbic acid, its potassium salt and ethyl sorbate isomerise under UV irradiation. All four geometrical isomers of the acid, salt and ester were separated using high-performance liquid chromatography on a nonpolar reversed-phase column (C18) and the ester also by gas chromatography on a VOCOL capillary column. The limit of detection and the interval of linearity were determined for all chromatographic methods. Individual isomers were identified with NMR analysis. Resolved chemical shifts of protons adjacent to the double bonds enabled qualitative and quantitative determination of isomers in the mixture. Antimicrobial activity of potassium sorbate isomers was tested on yeast Saccharomyces cerevisiae. Results show that the pure trans,trans isomer has a higher antimicrobial activity than the mixture of isomers. PMID- 11206807 TI - Spatial and temporal progressions of spatial statistical moments in linear chromatography. AB - Generalizations of existing models of chromatography allow the spatial and temporal progressions of all spatial statistical moments in linear chromatography to be given as the solution to a set of ordinary differential equations. Basic strategies of simplifying these equations are described. PMID- 11206808 TI - Consequences of variable purity of heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin determined by liquid chromatography-mass spectrometry on the enantioselective separation of polychlorinated compounds. AB - The composition of 10 batches of heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin (PM-CD) from different suppliers was determined by high-performance liquid chromatography combined with atmospheric pressure chemical ionisation mass spectrometry (MS). Considerable differences were found. Some batches consisted of more than 95% pure PM-CD, whereas others were not completely derivatised or contained a significant amount of by-products. Some suggestions about the structures of these impurities are given though neither nuclear magnetic resonance spectroscopy nor MS-MS investigations could completely reveal their nature. Capillaries for high-resolution gas chromatography were coated with the batches of most differing composition. They demonstrated widely varying column performance and separation properties for selected chiral polychlorinated substances such as chlordane compounds, o,p'-DDT, o,p'-DDD, alpha hexachlorocyclohexane and atropisomeric polychlorinated biphenyls. The best enantioselectivity was obtained with the purest PM-CD. Compared to separations reported in the literature, a broader enantioselectivity was observed and also trans-heptachlor epoxide and oxychlordane could be resolved into enantiomers. PMID- 11206810 TI - Autoxidation products of normal and genetically modified canola oil varieties determined using liquid chromatography with mass spectrometric detection. AB - Normal, high stearic acid and high lauric acid canola oil varieties were heated in the presence of air to allow autoxidation to occur. After the reaction, the oils were analyzed using a non-aqueous reversed-phase high-performance liquid chromatographic separation followed by detection using atmospheric pressure chemical ionization mass spectrometry. Oxidized products were separated and identified. The major autoxidation products which remained intact were epoxides and hydroperoxides. Two classes of epoxy triacylglycerols (TAGs) were formed. One class with the epoxy group replacing a site of unsaturation and one class adjacent to a site of unsaturation, as was previously reported for model TAGs. Intact oxidation products resulted mostly from oxidation of oleic acid, while oxidation products of linoleic and linolenic acid chains decomposed to yield chain-shortened species. Both neutral and polar chain-shortened products were observed. Polar chain-shortened decomposition products eluted at very short retention times and required a different chromatographic gradient to separate the molecules. This class of molecules was tentatively identified as core aldehydes. The high stearic acid canola oil yielded more intact oxidation products containing stearic acid, as expected. The high lauric acid oil produced intact oxidation products which contained lauric acid. PMID- 11206811 TI - Computer-assisted discrimination among malignant lymphomas and leukemia using immunophenotyping, intelligent image repositories, and telemicroscopy. AB - The process of discriminating among pathologies involving peripheral blood, bone marrow, and lymph node has traditionally begun with subjective morphological assessment of cellular materials viewed using light microscopy. The subtle visible differences exhibited by some malignant lymphomas and leukemia, however, give rise to a significant number of false negatives during microscopic evaluation by medical technologists. We have developed a distributed, clinical decision support prototype for distinguishing among hematologic malignancies. The system consists of two major components, a distributed telemicroscopy system and an intelligent image repository. The hybrid system enables individuals located at disparate clinical and research sites to engage in interactive consultation and to obtain computer-assisted decision support. Software, written in JAVA, allows primary users to control the specimen stage, objective lens, light levels, and focus of a robotic microscope remotely while a digital representation of the specimen is continuously broadcast to all session participants. Primary user status can be passed as a token. The system features shared graphical pointers, text messaging capability, and automated database management. Search engines for the database allow one to automatically identify and retrieve images, diagnoses, and correlated clinical data of cases from a "gold standard" database which exhibit spectral and spatial profiles which are most similar to a given query image. The system suggests the most likely diagnosis based on majority logic of the retrieved cases. The system was used to discriminate among three lymphoproliferative disorders and healthy cells. The system provided the correct classification in more than 83% of the cases studied. System performance was evaluated using rigorous statistical assessment and by comparison with human observers. PMID- 11206809 TI - Effects of acid treatment on the trace metal content of chromatographic silica: bulk analysis, surface analysis and chromatographic performance of bonded phases. AB - A series of studies has been carried out on the effect of refluxing silica chromatography particles for 0.5 h and 18 h in water, dilute hydrochloric acid and dilute hydrofluoric acid. The bulk and surface trace metal concentrations were measured by inductively-coupled plasma atomic emission spectroscopy, static secondary ion mass spectrometry (SSIMS) and X-ray photoelectron spectroscopy. Diffuse reflectance Fourier transform infrared spectroscopy was used to determine changes in 'isolated" and "bonded" silanol groups. The chromatographic behaviour of a series of weakly basic analytes was investigated on C8 and C18 bonded phases manufactured from the acid-treated silicas. The different reflux treatments all resulted in a reduction in the numbers of isolated silanols compared with the untreated silica and SSIMS analysis suggested that the HF-treated silicas had undergone a more efficient surface rehydroxylation. Bulk trace metals were removed most effectively by the HF treatment, with the multivalent elements (Ti and Al) being the most difficult to remove. Surface specific analysis suggested that trace metals were removed more rapidly from the surface of the silica compared to the bulk matrix and that the acid treatments resulted in halide contamination of the silica surface. Evidence is presented to suggest that the bulk metal content of the silica is not representative of the concentration of metals at the chromatographic surface. The chromatographic investigations showed that the HF-treated silica gave substantially better performance towards weak bases than the HCl-treated silicas. PMID- 11206812 TI - Autonomous decision-making: a data mining approach. AB - The researchers and practitioners of today create models, algorithms, functions, and other constructs defined in abstract spaces. The research of the future will likely be data driven. Symbolic and numeric data that are becoming available in large volumes will define the need for new data analysis techniques and tools. Data mining is an emerging area of computational intelligence that offers new theories, techniques, and tools for analysis of large data sets. In this paper, a novel approach for autonomous decision-making is developed based on the rough set theory of data mining. The approach has been tested on a medical data set for patients with lung abnormalities referred to as solitary pulmonary nodules (SPNs). The two independent algorithms developed in this paper either generate an accurate diagnosis or make no decision. The methodolgy discussed in the paper depart from the developments in data mining as well as current medical literature, thus creating a variable approach for autonomous decision-making. PMID- 11206813 TI - The design and performance of a 2.5-GHz telecommand link for wireless biomedical monitoring. AB - This paper details the implementation and operational performance of a minimum power 2.45-GHz pulse receiver and a companion on-off keyed transmitter for use in a semi-active, duplex RF biomedical transponder. A 50-ohm microstrip stub-matched zero-bias diode detector forms the heart of a body-worn receiver that has a (CMOS baseband amplifier consuming 20 microA from +3 V and achieves a tangential sensitivity of -53 dBm. The base transmitter generates 0.5 W of peak RF output power into 50 ohms. Both linear and right-hand circularly polarized Tx-Rx antenna sets were employed in system reliability trials carried out in a hospital Coronary Care Unit. For transmitting antenna heights between 0.3 and 2.2 m above floor level, transponder interrogations were 95% reliable within the 67-m2 area of the ward, falling to an average of 46% in the surrounding rooms and corridors. Overall, the circular antenna set gave the higher reliability and lower propagation power decay index. PMID- 11206814 TI - Skeletal growth estimation using radiographic image processing and analysis. AB - An automated knowledge-based vision system for skeletal growth estimation in children is reported in this paper. Images were obtained from hand radiographs of 32 male and 25 female children of age 1-16 yr. Phalanx bones were automatically localized and segmented using hierarchical inferences and active shape models, respectively. A number of shape descriptors were obtained from the segmented bone contour to quantify skeletal growth. From these descriptors, a feature vector was selected for a regression model and a Bayesian estimator. The estimation accuracy was 84% for females and 82% for males. This level of accuracy is comparable to that of expert pediatric radiologists, which suggests that the proposed approach has a potential application in pediatric medicine. PMID- 11206815 TI - An adaptive nonlinear diffusion algorithm for filtering medical images. AB - The nonlinear anisotropic diffusive process has shown the good property of eliminating noise while preserving the accuracy of edges and has been widely used in image processing. However, filtering depends on the threshold of the diffusion process, i.e., the cut-off contrast of edges. The threshold varies from image to image and even from region to region within an image. The problem compounds with intensity distortion and contrast variation. We have developed an adaptive diffusion scheme by applying the Central Limit Theorem to selecting the threshold. Gaussian distribution and Rayleigh distribution are used to estimate the distributions of visual objects in images. Regression under such distributions separates the distribution of the major object from other visual objects in a single-peak histogram. The separation helps to automatically determine the threshold. A fast algorithm is derived for the regression process. The method has been successfully used in filtering various medical images. PMID- 11206816 TI - Hadamard-based image decomposition and compression. AB - In this paper, we develop a general algorithm for decomposition and compression of grayscale images. The decomposition can be expressed as a functional relation between the original image and the Hadamard waveforms. The dynamic adaptive clustering procedure incorporates potential functions as a similarity measure for clustering as well as a reclustering phase. The latter is a multi-iteration, convergent procedure which divides the inputs into nonoverlapping clusters. These two techniques allow us to efficiently store and transmit a class of half-tone medical images such as magnetic resonance imaging (MRI) of the human brain. Due to the redundant image structure of MRI, obtained after the decomposition and clustering, almost half of the image can be omitted all together. Naturally, the compression rates for this specific type of grayscale image are increased greatly. A run-length coding is performed in order to compress further the retained information from the first two steps. Although all the techniques applied are simple, they represent an efficient way to compress grayscale images. The algorithm exhibits a performance which is competitive and often outperforming some of the methods reported in the literature. PMID- 11206817 TI - A screening gate to prevent entry of mobile telephone handsets in the speaking/stand-by mode into prohibited and restricted areas. AB - Electromagnetic interference to electronic equipment by mobile telephone handsets is well known. We present an automatic screening gate that detects concealed mobile telephone handsets and classifies them by type. The screening method used in the gate does not require any additions to or reconstruction of mobile telephone systems. PMID- 11206818 TI - Delayed reduction and stabilization of the tibiofibular syndesmosis. AB - Six patients with chronic widening and instability of the tibiofibular syndesmosis subsequent to pronation--external rotation ankle fractures were reviewed as regards diagnosis and treatment. An evaluation of the syndesmotic interval was best done by CT scans using axial cuts. Delayed reduction and stabilization using primarily large screw fixation resulted in maintenance of the reduction and satisfactory results in 5 of 6 cases. In one case, an arthrodesis of the tibiofibular interval was done because of significant incongruity. PMID- 11206819 TI - Cavovarus foot treated with combined calcaneus and metatarsal osteotomies. AB - Twenty-one feet in fifteen patients underwent osteotomies of the calcaneus and one or more metatarsals for symptomatic cavovarus foot deformity. Seven (nine feet) were male, and eight (twelve feet) were female. The etiology included hereditary motor sensory neuropathy (HMSN) (fifteen feet), post-polio syndrome (two feet), sacral cord lipomeningocele (two feet), parietal lobe porencephalic cyst (one foot), and idiopathic peripheral neuropathy (one foot). Presenting complaints were metatarsalgia (fifteen feet), ankle instablility (five), and ulceration beneath the second metatarsal head (one foot). Eleven feet were assessed using the Maryland Foot Rating Score. Maryland Foot Rating Score (University of Maryland, Baltimore, MD) improved from 72.1 (avg.) preoperatively to 89.9 (avg.) post-operatively (follow-up 70.9 months avg.). Eight feet were assessed using the AOFAS (American Orthopaedic Foot and Ankle Society) Ankle Hindfoot and Midfoot Scores. The AOFAS Ankle-Hindfoot Score improved from 46.3 (avg.) pre-operatively to 89.1 (avg.) post-operatively, and the AOFAS Midfoot Score improved from 40.9 (avg.) pre-operatively to 88.8 (avg.) post-operatively (follow-up 20.8 months avg.). The postoperative AOFAS Ankle-Hindfoot Score for all nineteen feet was 90.8 (avg.) and the post-operative AOFAS Midfoot Score for all nineteen feet was 90.2 (avg.). Two patients were lost to follow-up and were not included in the study. Ankle, hindfoot, and midfoot motion was maintained or improved in sixteen feet. Complications included delayed union in two and nonunion in three of 66 metatarsal osteotomies. While three patients required an AFO (ankle-foot orthosis) for ambulation preoperatively, all patients were brace free postoperatively. All patients expressed willingness to undergo the same procedure again if it were necessary. Weight-bearing radiographs were available for 17 feet. Radiographic analysis revealed a decrease in forefoot adduction (9.6 degrees avg.) and a reduction in both hindfoot (9.1 degrees avg.) and forefoot cavus (10.6 degrees) leading to an overall 13 percent reduction in the height of the longitudinal arch. Lateral sliding elevating calcaneal osteotomy combined with dorsolateral closing wedge osteotomies of one or more metatarsal bases in the severe symptomatic cavovarus foot can provide a pain-free, plantigrade foot with a lowered longitudinal arch and a stable ankle without sacrificing motion. PMID- 11206820 TI - Extrinsic muscle activity, foot motion and ankle joint moments during the stance phase of walking. AB - This study examined stance phase foot kinematics, kinetics and electromyographic (EMG) activity of extrinsic muscles of 18 healthy males. Three-dimensional kinematic and kinetic data were obtained via video analysis of surface markers and a force plate. Ankle joint moments are described about orthogonal axes in a segmental coordinate system. Kinematic data comprise rearfoot and forefoot motion, described about axes of a joint coordinate system, and medial longitudinal arch height. Surface EMG was obtained for tibialis anterior, soleus, gastocnemius medialis and lateralis, peroneus longus and peroneus brevis and extensor digitorum longus. It was concluded that the demands on the controlling muscles are greatest prior to foot flat and after heel rise. Tibialis anterior restrained rearfoot plantarflexion from heel contact to 10% stance, and eversion between 10% stance and footflat. Activity in peroneus longus was consistent with its role in causing eversion after heel contact, then as a stabiliser of the forefoot after heel rise. Activity in peroneus brevis suggested a role in restraining lateral rotation of the leg over the foot, late in stance. PMID- 11206821 TI - Sonographic measurement of instability of the subtalar joint. AB - A sonographic method of measuring instability of the subtalar joint was developed. After defining reference points, we determined a sonographic fibulo trochlear angle. This angle was measured in a neutral position and under an inversion stress position. A ratio q representing the relationship between the fibulo-trochlear angle measured in the neutral position and under stress, was determined. The method was tested on volunteers with clinically and radiologically stable subtalar joints and a control group with unstable subtalar joints. The stress radiograph using the Zwipp method was utilized for radiologic correlation. A sonographic ratio q>1.6 correlated with a radiological unstable subtalar joint. The borderline zone in which there was an overlap of stable and unstable subtalar joints was characterized by a q value of 1.2-1.6. A ratio q<1.2 correlated with a stable subtalar joint. PMID- 11206822 TI - Dorsiflexion contracture after the Weil osteotomy: results of cadaver study and three-dimensional analysis. AB - For metatarsalgia caused by a dislocated lesser metatarsophalangeal (MTP) joint and isolated over-long lesser metatarsals, surgical treatment options without sacrificing the joint are limited. Recently, the Weil osteotomy has been advocated for the treatment of this deformity. In our experience, preliminary results with this technique have revealed a high rate of dorsiflexion contracture of the MTP joints at follow-up. We performed a cadaver study and a three dimensional analysis on sawbones to investigate this phenomenon. In the cadaveric portion of this study, the second MTP joints of two fresh-frozen cadavers were dissected; the entire ray, with the metatarsal shaft, MTP joint, toe, and plantar fascia, was removed en bloc. After gross anatomic structures were photographed, a Weil osteotomy was performed at 25 degrees relative to the long axis of the metatarsal shaft. The positions of muscles, ligaments, and tendons were noted and photographed before and after the osteotomy. In the sawbones portion of this study, a Weil osteotomy was performed at four different angles (25 degrees, 30 degrees, 35 degrees, and 40 degrees) relative to the long axis of the metatarsal. To ensure reproducibility, the sawbone models were fixed proximally to a vertical milling machine with the second metatarsals inclined 15 degrees to simulate the anatomic position. After making the cut, the plantar fragment was translated along the dorsal fragment proximally for a distance of 5 mm. Before and after the osteotomy, selected x, y, and z coordinates were obtained using a Microscribe 3D digitizer. Data analysis was performed with Microsoft Excel, and ANOVA was used to determine significant differences (p < 0.05) between the various osteotomies. Analysis of the cadaver dissection revealed that after the Weil osteotomy, the tendons of the interosseous muscles move dorsally with respect to the axis of the MTP joint due to the depression of the plantar fragment of the metatarsal. The loss of their flexion effect on the joint permits the pull of the extensor to dorsiflex the toe. The size of the depression for the various osteotomies averaged: 25 degrees osteotomy, 3.03 mm (range, 1.8 to 3.8 mm); 30 degrees osteotomy, 3.2 mm (range, 1.9 to 4.0 mm); 35 degrees osteotomy, 3.5 mm (range, 1.7 to 5.7 mm); and 40 degrees osteotomy, 4.2 mm (range, 2.8 to 6.4 mm). Amounts of shortening relative to the long axis of the metatarsal for the various osteotomies averaged: 25 degrees osteotomy, 5.03 mm (range, 4.77 to 5.30 mm); 30 degrees osteotomy, 4.59 mm (range, 3.47 to 5.19 mm); 35 degrees osteotomy, 4.27 mm (range, 2.87 to 5.00 mm); and 40 degrees osteotomy, 3.65 mm (range, 3.20 to 4.31 mm). According to our analysis, depression of the plantar fragment always occurs after a Weil osteotomy. This depression changes the center of rotation of the MTP joint, and the interosseous muscles then act more as dorsiflexors than as plantarfexors. PMID- 11206823 TI - Tibialis posterior tendon dysfunction: a primary or secondary problem? AB - Seventeen patients with a mean follow-up of 64.4 months following a tibialis posterior tendon transfer to regain active foot dorsiflexion were clinically examined specifically for signs of tibialis posterior tendon dysfunction. The results show that 8 patients (47%) had Grade 4 or better power of eversion but none had a clinical flatfoot on the Harris-Beath footprints. Only 6% had forefoot abduction; 17% exhibited hindfoot valgus and 82% were able to perform the single heel rise. Tibialis posterior tendon dysfunction therefore does not appear to be an inevitable sequel of tibialis posterior tendon transfer even in the presence of a functioning peroneal muscle. Other studies have noted that a pre-existent flatfoot was often present in patients with tibialis posterior tendon dysfunction. None of the patients in this study had pre-existent flatfoot. We suggest that a predisposition, in the form of a pre-existent tendency to flatfoot may also be a factor in the pathogenesis of tibialis posterior tendon dysfunction. This may explain the long-term failure of flexor digitorum longus and flexor hallucis longus tendon transfers in the treatment for tibialis posterior tendon dysfunction when the biomechanics of the foot has not been altered. PMID- 11206824 TI - Stress fracture of the talus following resection of a talocalcaneal coalition: a case report. AB - We report the case of a 15-year-old male with bilateral talocalcaneal coalition. Following resection of the symptomatic coalition, the patient developed a painful ankle. MR imaging revealed a stress fracture of the talar body. In this report we discuss presentation and treatment of a symptomatic talocalcaneal coalition complicated by a later stress fracture as well as a review of the literature. PMID- 11206825 TI - Fibroma of a tendon-sheath presenting as toe deformity. AB - We describe a rare manifestation fibroma in a tendon-sheath in an 83-year-old man. The patient complained initially of a slowly progressive spreading, apart of the right second and third toes. A mass was found in the plantar aspect of the foot. It was completely excised at surgery. Histological examination revealed sparse spindle or stellate cells with slit-like vessels in the dense collagenous matrix. There had been no recurrence at follow-up 17 months after surgery. PMID- 11206826 TI - Flexor to extensor tendon transfer: a new method of tensioning and securing the tendon. PMID- 11206827 TI - Lateral premalleolar bursitis as a result of sitting on the foot. AB - Lateral premalleolar bursitis develops on the dorsolateral aspect of the foot in people who sit on their feet for prolonged periods. Twenty-nine premalleolar bursae in 21 patients were diagnosed. The patients presented with one or more of the complaints of swelling, pain and difficulty in wearing shoes. One bursa was infected. Initial treatment was non-surgical. With avoidance of the sitting position, the problem resolved in eight of the sixteen patients who were followed. Four bursae were injected with cortisone, three without success. Six bursae were surgically excised, and four of them, with a minimum of one year follow-up were doing well. PMID- 11206828 TI - Digital photography in orthopaedic surgery. AB - Digital photography has become a practical alternative to film photography for documentation, communication, and education about orthopaedic problems and treatment. Digital cameras may be used to document preoperative and postoperative condition, intraoperative findings, and imaging studies. Digital photographs are captured on the charged coupler device (CCD) of the camera, and processed as digital data. Images may be immediately viewed on the liquid crystal display (LCD) screen of the camera and reshot if necessary. Photographic image files may be stored in the camera in a floppy diskette, CompactFlash card, or SmartMedia card, and transferred to a computer. The images may be manipulated using photo editing software programs, stored on media such as Zip disks or CD-R discs, printed, and incorporated into digital presentations. The digital photographs may be transmitted to others using electronic mail (e-mail) and Internet web sites. Transparency film slides may be converted to digital format and used in digital presentations. Despite the initial expense to obtain the required hardware, major cost savings in film and processing charges may be realized over time compared with film photography. PMID- 11206829 TI - Dragons and the VAT. PMID- 11206830 TI - Primary subtalar arthrodesis of calcaneal fractures. AB - We evaluated retrospectively the long-term results of isolated calcaneal fractures treated with open reduction and internal fixation and a primary subtalar arthrodesis. From 1990 to 1997 258 patients were treated with a calcaneal fracture, for the current study six patients were included. Six different surgeons operated on the patients. The indication for the fusion was based on the comminution of the posterior facet according to the preoperative CT as well as the intraoperative evaluation of destruction of the cartilage. The restoration of length, axes and angles of the calcaneus was almost anatomical in all cases. Follow-up was done at a mean of 4.9 (2.5 - 7.5 years). Using the AOFAS score, the results were good or excellent in five patients. In one patient with a painful arthritis in the talonavicular joint and hyperesthesia of the sural nerve, the results were fair. All returned to their profession within 9 months and had no or only minor daily restrictions. The results are comparable with single surgeon series. We found open reconstruction of the calcaneus with primary fusion of the subtalar joint may be indicated in selected patients and, in these 6 patients led to good results. PMID- 11206831 TI - Social isolation stress augments angiogenesis induced by colon 26-L5 carcinoma cells in mice. AB - We have previously shown that tumor necrosis factor-alpha (TNF-alpha), which is an important angiogenesis-related factor, was over-secreted in male BALB/c mice under social isolation stress as compared with the control, and closely associated with a remarkable elevation of tumor invasion and metastasis of colon 26-L5 carcinoma cells. In the present study, we explored the effect of isolation stress on the angiogenesis caused by colon 26-L5 carcinoma cells in vivo and in vitro. Social isolation lead to the enhancement of tumor growth after intrahepatic implantation with a fragment of colon 26-L5 tumor. Angiogenic response (number of vessels oriented towards tumor mass) and tumor growth (size) were significantly increased in the socially isolated mouse relative to that in the group-housed mice. Furthermore, higher protein level of hepatic TNF-alpha was found in the stressed mice than that in the control. Expression of mRNA for vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were also elevated in the tumor regions and liver tissues of the stressed mice in comparison with that in group-housed mice. On the other hand, hepatic sinusoidal endothelial (HSE) cells treated with TNF-alpha exhibited a marked promotion of the migration, invasion, expression of mRNA for matrix metalloproteinase (MMP)-9, and tube-like formation, but no cytotoxicity against the cells in vitro. The above data suggest that the social isolation stress augmented the tumor-induced angiogenesis probably by up-regulating the angiogenesis-related factors, including TNF-alpha, VEGF and HGF, and consequently mediating the functions of endothelial cells such as migration, invasion, and tube-like formation. PMID- 11206833 TI - Behaviour of metastasis in relation to vascular index in patients with node positive breast cancer treated with adjuvant tamoxifen. AB - Some experimental studies suggested that one possible oestrogen-receptor unrelated mechanism of action of tamoxifen involves inhibition of angiogenesis. We evaluated the correlation of the degree of vascularisation of the primary tumour and we assessed it by using the panendothelial marker anti-CD31 and immunohistochemistry with microvessels count, performed at the vascular 'hot spot' of each single cancer, with the risk of recurrence in time. A cohort of 176 consecutive patients with node-positive invasive breast cancer treated with adjuvant tamoxifen (30 mg/daily for 3 years) and a median follow-up of 72 months was studied. Sixty-two patients developed metastasis (30 visceral, 18 skeletal and 14 in soft tissues) during the time of observation. The study of the hazard function for metastasis was performed by a generalized linear modelling approach with a binomial error according to Efron. The risk of first recurrence was strictly associated with vascular index, having the patients with the highest microvessel counts the highest risk of metastasis during all the period of observation. We did not find an interaction of vascularity with oestrogen receptor (ER) status. However, in the subgroup of patients with ER-positive tumours the hazard of metastasis was almost constant in time, while in that with ER-negative tumours it increased rapidly up to 20 months and, thereafter, decreased sharply. The results of our study are an indirect evidence that the patients with highly vascularized breast cancers may gain poor benefit of adjuvant tamoxifen and, therefore. that this antioestrogen is unlikely to retain a clinically relevant antiangiogenic activity in human breast cancer. Our data need confirmation by a prospective randomized clinical trial. PMID- 11206832 TI - The impact of laparoscopic biopsy of pancreatic lymph nodes with helium and carbon dioxide on port site and liver metastasis in BOP-induced pancreatic cancer in hamster. AB - The influence of pancreatic biopsy during laparoscopy with carbon dioxide (CO2) and helium on the incidence of port site and liver metastasis in pancreatic carcinoma is still unknown. Ductal adenocarcinoma of the pancreas was induced in Syrian hamsters (n = 30) by injection of N-nitrosobis-2-oxopropylamin (BOP, 10 mg/kg body weight/week) for 12 weeks. In week 13, hamsters were randomized in 3 groups (n = 10): While in group 1 (gr. 1) a laparotomy and biopsy of pancreatic lymph nodes was performed, gr. 2 and gr. 3 underwent a laparoscopic biopsy either with CO2 or helium. Therefore, one trocar was located in the left (biopsy) and the right abdominal wall (camera). In the 18th week all animals were sacrificed and the incidence of abdominal wall, port site and liver metastases was histologically determined. While there were abdominal wall metastases after laparotomy in 10% (n = 1), we observed trocar metastases in the CO2 group in 20% (n = 2). However, there were no trocar metastases in the helium group. The incidence of liver metastasis did not differ between the laparotomy and the helium group (20% vs 30%), but was increased in the CO2 group (60%). Laparoscopic biopsy of pancreatic lymph nodes with CO2 increased the incidence of port site and liver metastases in pancreatic cancer. The helium group was equal to the laparotomy group in this respect. Thus, staging laparoscopy with helium might become an alternative to explorative laparotomy in pancreatic cancer. PMID- 11206834 TI - Cyclooxygenase-2 expression in colorectal cancer liver metastases. AB - Cyclooxygenase-2 (COX-2) is up-regulated in 85-90% of primary human colorectal cancers and is a putative target for the chemopreventative activity of non steroidal anti-inflammatory drugs. However, COX-2 expression by human colorectal cancer liver metastases has been poorly characterized. We studied a consecutive series of 38 patients who underwent liver resection for metastatic disease, for whom long-term (up to 57 months), prospective follow-up data were available. Semi quantitative immunohistochemistry for COX-2 was performed on 54 metastases from 35 patients, for whom adequate histological material was available. Diffuse cytoplasmic staining for COX-2 protein was detected in cancer cells in 100% of metastases (COX-2 score 1, n = 25; score 2, n = 29). There was no relationship between metastasis size or differentiation grade and the level of COX-2 protein expression. There was no difference in colorectal cancer-free or overall survival between patients with high (score 2) and low (score 1) COX-2 scores (Kaplan-Meier survival analysis and log rank test, both P = 0.97). Multivariate Cox regression analysis identified age, incomplete resection and presence of extra-hepatic disease as independent predictors of disease-free and overall survival following surgery. COX-2 protein was also localized to a subset of stromal fibroblasts and mononuclear cells within metastases as well as hepatocytes from resection specimens. COX-2 protein was expressed by cancer cells in all human colorectal cancer liver metastases which were studied. Investigation of the effect of selective COX-2 inhibition on metastasis growth and metastasis cancer cell proliferation/apoptosis in vivo are warranted. PMID- 11206835 TI - Isolation and characterization of cell lines with reduced urokinase binding. AB - Six cell lines have been generated from the human fibrosarcoma HT-1080 by mutagenesis. They were selected on the basis of reduced urokinase (uPA) binding on replicate polyester filters. Single cell clones were then isolated by limited dilution cloning. All cloned cells showed less uPA binding on filters, and as cell monolayers. These cell lines were able to bind only 10 to 65% as much uPA as the wild-type HT-1080 cells. Surface-bound uPA proteolytic activity and surface activation of plasminogen from these cells were also reduced relative to the wild type. uPA could activate MAP kinases in the wild-type and two of the cell lines with the least uPA-binding, but the amount of the activated forms of the signalling molecules were reduced. Immunoblotting using two different anti-uPA receptor antibodies showed two cross-reacting protein species of approximately 53 kDa and approximately 38 kDa. The proportion of the lower Mr band to the higher Mr band was found to be reduced in all the cell lines relative to the wild-type. Chemical cross-linking with single-chain urokinase (scuPA) showed only one high molecular-weight adduct, with Mr approximately 90 kDa, in all the cell lines tested. Similarly, cross-linking with the amino terminal fragment of uPA yielded a single approximately 70 kDa adduct. These would indicate that only the approximately 53 kDa band was responsible for cross-linking reactions. Equilibrium binding experiments showed that only one set of high-affinity binding sites for the wild-type cells. However, the binding of scuPA to two of these cell lines was best fitted to a two-site model, one of which was similar to the high affinity binding sites of the wild-type, although the number of sites was reduced, while the other was of much lower affinity but was large in number. These results are discussed in relation to changes in the structure of ligand binding machinery in these cells, which affect other cellular functions. PMID- 11206836 TI - A new method for assaying adhesion of cancer cells to the greater omentum and its application for evaluating anti-adhesion activities of chemically synthesized oligosaccharides. AB - A new ex vivo method for assaying adhesion of cancer cells to the greater omentum has been developed using mouse greater omentum and [3H]labelled human gastric and mouse colorectal cancer cells. Since the adhesion rates were found to increase up to 18 h and labelled cells seemed to be stable during the period, the present method could be useful for investigating adhesion of cancer cells to the greater omentum, which must occur at the first step of the peritoneal dissemination. The adhesion of cancer cells to the greater omentum was inhibited by a series of chemically synthesized oligosaccharides and Gal beta1,3[3OMeGal beta1,4GlcNAc beta1,6]alphaBn was found to be the best inhibitor. The anti-tumor effect of this novel tetrasaccharide in vivo was shown in preliminary experiments using Balb/c mice and colon26 cells. PMID- 11206837 TI - Activated leukocyte cell adhesion molecule (ALCAM) and annexin II are involved in the metastatic progression of tumor cells after chemotherapy with Adriamycin. AB - Metastasis frequently occurs during and/or after chemotherapy resulting in failure. This suggests that inadequate chemotherapy promotes the emergence of more malignant tumor cells with metastatic potential. However, it is not determined how chemotherapy could promote the metastatic progression of tumor cells. In this study, we isolated highly metastatic clones from the tumors treated with ADR using an in vivo experimental model, in which non-metastatic tumor cells were inoculated s.c. in mice, treated with or without Adriamycin and then culture lines were re-established from the tumors. Then we isolated cDNAs for activated leukocyte cell adhesion molecule (ALCAM), osteopontin, and annexin II as candidates for metastasis-promoting genes with the use of a PCR-based subtraction method. Further we examined the metastatic potential of transfectants over-expressing ALCAM, osteopontin, or annexin II and combinations of them. Metastasis to the lung was observed in the mice where transfectants over expressing ALCAM plus annexin II had been inoculated via tail vein. These results suggest that the over-expression of ALCAM and annexin II play a role in the metastatic progression after chemotherapy with ADR. PMID- 11206838 TI - Expression of metastasis-associated mts1 gene is co-induced with membrane type-1 matrix metalloproteinase (MT1-MMP) during oncogenic transformation and tubular formation of Madin Darby canine kidney (MDCK) epithelial cells. AB - Madin-Darby canine kidney (MDCK) epithelial cells form branching tubules in three dimensional collagen gel in the presence of hepatocyte growth factor (HGF). Membrane type-1 matrix metalloproteinase (MT1-MMP), expression of which was induced by collagen-gel culture, was demonstrated to play an essential role in tubular formation (Y. Kadono et al. Biochem Biophys Res Commun 1988; 251: 681-7 [13]). Oncogenic transformation of MDCK cells by erbB2 and v-src induced expression of MT1-MMP, loss of cell-cell adhesion and scattered invasion into collagen gel, mRNA differential display and Northern hybridization identified metastasis-associated mts1 as one of the genes co-induced with MT1-MMP by oncogenic transformation or collagen-gel culture of MDCK cells. Expression of antisense RNA to mts1 in MDCK cells interfered with the extension of tubules into the collagen gel, however, it did not affect the morphological changes induced by HGF in culture on plastic dishes. ErbB2-transformant transfected with mts1 antisense construct, which showed unaltered morphology in culture on plastic dishes, did not scatter into collagen gel but formed aggregates. These results suggested that Mts1 contributes not only to tumor invasion but also to kidney tubulogenesis in cooperation with MT1-MMP. The coordinated action of MT1-MMP and Mts1, which is responsible for the highly invasive properties of mesenchymal cells, may be involved in epithelial tubulogenesis and invasion of malignant carcinoma cells. PMID- 11206839 TI - A highly metastatic Lewis lung carcinoma orthotopic green fluorescent protein model. AB - The Lewis lung carcinoma has been widely used for many important studies. However, the subcutaneous transplant or orthotopic cell-suspension injection models have not allowed the expression of its full metastatic potential. A powerful new highly metastatic model of the widely-used Lewis lung carcinoma is reported here using surgical orthotopic implantation (SOI) of tumor fragments and enhanced green fluorescent protein (GFP) transduction of the tumor cells. To achieve this goal, we first developed in vitro a stable high-expression GFP transductant of the Lewis lung carcinoma with the pLEIN retroviral expression vector containing the enhanced Aequorea victoria GFP gene. Stable high-level expression of GFP was found maintained in vivo in subcutaneously-growing Lewis lung tumors. The in vivo GFP-expressing tumors were harvested and implanted as tissue fragments by SOI in the right lung of additional nude mice. This model resulted in rapid orthotopic growth and extensive metastasis visualized by GFP expression. 100% of the animals had metastases on the ipsilateral diaphragmatic surface, contralateral diaphragmatic surface, contralateral lung parenchima, and in mediastinal lymph nodes. Heart metastases were visualized in 40%, and brain metastases were visualized in 30% of the SOI animals. Mice developed signs of respiratory distress between 10-15 days post-tumor implantation and were sacrificed. The use of GFP-transduced Lewis lung carcinoma transplanted by SOI reveals for the first time the high malignancy of this tumor and provides an important useful model for metastasis, angiogenesis and therapeutic studies. PMID- 11206840 TI - Anti-metastatic efficacy and safety of MMI-166, a selective matrix metalloproteinase inhibitor. AB - The anti-metastatic efficacy and safety of a newly-developed matrix metalloproteinase (MMP) inhibitor were examined. MMI-166, a N-sulfonylamino acid derivative, inhibited the enzyme activity of MMP-2, 9, and 14 but not MMP-1, 3 or 7. Daily oral administration of MMI-166 resulted in potent inhibition of metastatic lung colonization of Lewis lung carcinoma injected via the tail vein and liver metastasis of C-1H human colon cancer implanted into the spleen at inhibition levels of 43% and 63%, respectively. Daily administration of MMI-166 also resulted in prolonged survival of mice given intraperitoneal implantation of Ma44 human lung cancer cells. The anti-metastatic activity of MMI-166 was as effective as that of other MMP inhibitors with broad inhibitory spectrum. MMI-166 did not affect in vitro tumor cell growth. Neither body weight losses nor hematotoxicity was observed during long-term treatment, indicating the safety of MMI-166 in mice. These results indicate that the selective MMP inhibitor MMI-166 has therapeutic potential as an anti-metastasis agent. PMID- 11206841 TI - CD44 and beta1 integrins mediate ovarian carcinoma cell migration toward extracellular matrix proteins. AB - Epithelial cancer of the ovary spreads by implantation of tumor cells onto the mesothelial cells that line the peritoneal cavity. The aim of this study was to identify the cell-matrix interactions that mediate ovarian carcinoma cell migration toward components of the mesothelial cell-associated extracellular matrix. The human ovarian carcinoma cell lines NIH:OVCAR5 and SKOV3 were analyzed by flow cytometry for the expression of cell surface receptors. The ability of those receptors to mediate ovarian carcinoma cell migration toward fibronectin, type IV collagen, and laminin was determined. A monoclonal antibody against the beta1 integrin subunit abrogated the migration of both cell lines toward the extracellular matrix proteins. Blocking antibodies against alpha integrin subunits suggest that ovarian carcinoma cell migration toward fibronectin is primarily mediated by the alpha5beta1 integrin, type IV collagen by the alpha2beta1 integrin, and laminin by the alpha6beta1 integrin. These results suggest that ovarian carcinoma cell migration is regulated by multiple beta1 integrin-matrix interactions. Significant reduction of cell migration was observed with a monoclonal antibody against CD44 that blocks the hyaluronan binding site of CD44, but not with an antibody that binds at an alternate site on CD44. Intact hyaluronan and/or hyaluronan oligomers also inhibited cell migration, suggesting that the CD44-hyaluronan interaction provides an integrin independent mechanism of control for ovarian carcinoma cell migration. These results suggest that ovarian carcinoma cell migration is regulated by both integrin-dependent mechanisms, involving the interaction of beta1 integrins with extracellular matrix proteins, and an integrin-independent mechanism that involves the interaction of CD44 and hyaluronan. PMID- 11206842 TI - Absence of correlation of MUC1 expression to malignant behavior of renal cell carcinoma in experimental systems. AB - A correlation between MUC1 expression in renal cell carcinomas (RCCs) and the clinical stages was previously demonstrated. To assess whether MUC1 expression is causally related to malignant tumor behavior, MUC1 cDNA was stably transfected into a renal carcinoma cell line SN12C that expresses trace levels of MUC1. MUC1 with sialylated carbohydrate chains was detected on the surface of transfected cells in two independent experiments. There was no correlation between MUC1 expression and in vitro growth and motility. In vivo growth of the transfectants at the site of orthotopic transplantation in nude mice was slower than mock transfected cells. Therefore, MUC1 alone did not seem to confer a malignant phenotype to RCCs. PMID- 11206843 TI - Increased expression of fascin, motility associated protein, in cell cultures derived from ovarian cancer and in borderline and carcinomatous ovarian tumors. AB - Fascin bundles actin microfilaments within dynamic cellular structures such as microspikes, stress fibers and membrane ruffles. Fascin overexpression induces membrane protrusions and increased cell motility, and is highly expressed in various transformed cells, and in specialized normal cells including neuronal, endothelial and dendritic cells. In breast cancer, fascin expression correlates with high-grade tumors. To investigate whether fascin might be a predictor factor for ovarian cancer progression, eighteen cell cultures derived from ovarian cancer, and thirty four archival paraffin-embedded material of normal versus borderline and carcinomatous ovaries were stained by immunocytochemistry and immunohistochemistry with fascin Mab 55K-2. Overall expression of the fascin protein was found in 50% (9/18) of cell cultures derived from original samples of ovarian tumors. Expression of fascin protein was found in 67% (6/9) of cell cultures derived from patients diagnosed with stage IV disease, and 33% (3/9) of cell cultures from patients diagnosed with stage II/III. There was no clear relationship between fascin expression and histologic types, tumor grade, or DNA ploidy. However, 75% of cell cultures, which developed into a xenograft after intraperitoneal inoculation, showed fascin expression, while 86% of non tumorigenic cell cultures did not show fascin expression. Expression of fascin in these established ovarian tumor cell cultures was significantly associated with the ability for these cells to grow intraperitoneally (P < 0.05). Furthermore, fascin was never expressed in normal epithelial ovarian tissues, but was present in all pathologic ovaries. Both diffuse and focal patterns were observed in borderline ovarian tumors (67% and 33%), advanced primary ovarian cancer (67% and 33%) and metastatic ovarian cancer (89% and 11%). Therefore, our data suggest that fascin could serve as a prognostic factor for abnormal ovarian epithelial pathology and could be a novel target for the treatment of ovarian cancer. PMID- 11206844 TI - Interaction of tumor cells with vascular endothelia: role of platelet-activating factor. AB - We investigated whether tumor cell/endothelia interaction can be influenced by platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine), a lipid mediator that promotes adhesiveness and extravasation of leukocytes in the inflammatory reaction. We found that the PAF receptor antagonist WEB 2086 prevents adhesion of melanoma Hs294T and colon carcinoma LS180 lines to IL-1 stimulated endothelial cells. Moreover, PAF stimulated the adhesiveness of Hs294T and LS180 cells to VCAM-1 and E- selectin, respectively, in an artificial model consisting of recombinant adhesive proteins bound to protein A-coated substrata. Thus, tumoral and not endothelial cell surface seems to be involved in the PAF mediated enhancement of tumor cell adhesiveness to IL-1-activated endothelia. This observation is supported by the finding that Hs294T and LS180 cells express high affinity and functionally active receptors for PAF. By using specific inhibitors, we found that PAF-induced enhancement of cell adhesiveness was mediated by G-protein activation and protein tyrosine phosphorylation. In addition, protein tyrosine phosphorylation was observed in Hs294T and LS180 cells stimulated by PAF. In conclusion, we demonstrated that PAF-mediated activation of tumor cells enhances their adhesiveness to IL-1-stimulated vascular endothelia. PMID- 11206845 TI - New approaches to assess selenium status and requirement. AB - Selenium is one of the essential nutrients that may have beneficial effects on health at dietary intakes higher than the established Recommended Dietary Allowances in the United States. Dietary recommendations for this element have been the subject of much controversy, illustrating the difficulties involved in the definition of requirements based on the interpretation of biochemical markers. This review will show how concepts may differ and even change as a consequence of the evolution of the knowledge concerning classical parameters (e.g., identification of isoforms of the classical selenium-dependent enzyme glutathione peroxidase) or following the discovery of new biologic markers for selenium such as iodothyronine desiodinase, thioredoxin reductase, or the selenoproteins P and W. PMID- 11206846 TI - Current international approaches to food claims. AB - The market for functional foods is rapidly increasing. It is necessary to establish a legal framework for these foods. This has proved difficult in a number of countries. The control through health claims is generally accepted as the most appropriate measure. Activity in this area has been developing both at the national and international levels. However, the regulations and proposals from a number of national authorities and other nongovernmental sectors are varied and difficult to reconcile. This paper examines the range of health claim controls being used in the food area. They are considered in detail so as to establish a better understanding of the claims. In this paper, the claims have been classified into six categories: nutrient content claims, comparative claims, nutrient function claims, claims related to dietary guidelines or healthy diets, enhanced function claims, and reduction of disease risk claims. Of these, the latter four claims are considered to have significant implications for functional foods. PMID- 11206847 TI - Holiday weight gain: fact or fiction? AB - The prevalence of obesity continues to rise and controversy remains regarding the underlying specific causes of this trend. Recently, the magnitude of holiday weight gain and its contribution to annual weight gain were examined in a convenience sample of 195 adults. On average, weight gain during the 6-week winter period from Thanksgiving through New Year averaged only 0.37 kg. However, weight gain was greater among individuals who were overweight or obese, and 14% gained >2.3 kg (5 lb). In addition, among the entire population, weight gain during the 6-week holiday season explained 51% of annual weight gain. These results suggest that holiday weight gain may be an important contributor to the rising prevalence of obesity, even though absolute values for weight gain in this study were less than anticipated. Further studies using representative populations are needed to confirm these findings. PMID- 11206849 TI - A Robertsonian translocation, rob(2;28), found in Vietnamese cattle. AB - A new Robertsonian translocation, rob(2;28), was discovered in a local population of the Vietnamese Cattle. The animal (2n = 59, XY) was found by Q- and R-banding to be a heterozygous carrier of a centric fusion translocation involving chromosomes 2 and 28. FISH analysis using a bovine satellite I DNA probe demonstrated that the centromeric heterochromatin block of the rob(2;28) chromosome become much smaller than its ancestors suggesting a monocentric nature of this centric fusion. This is the first report identifying a Robertsonian translocation in Southeast Asian cattle by karyotyping of banded chromosomes. PMID- 11206848 TI - Evolution of parental ITS regions of nuclear rDNA in allopolyploid Aegilops (Poaceae) species. AB - The genus Aegilops comprises approximately 25 diploid, tetraploid and hexaploid species, in which the genome types of all allopolyploids involve either U or D genome, or both of them. The internal transcribed spacer (ITS) region of 18S-26S nuclear ribosomal DNA (rDNA) from 11 allopolyploid species and 7 related diploid species in the genus were directly sequenced by pooled PCR products. Phylogenetic analyses for tracing evolutionary patterns of parental rDNA in allopolyploid species were performed using the neighbor-joining method. The D genome involved tree included three clades (CC-DDCC, DDMM-DDMMSS-DDMMUU, and MM-MhMh-DDNN), but did not include Ae. squarrosa (DD). It indicated that the rDNA of ancestral D genome had been somewhat differentiated in allopolyploids. The U genome involved tree showed that the allopolyploids and their common ancestor, Ae. umbellulata, formed a clade, suggesting that rDNA in UUMM and UUSS genomes has been homogenizing toward that of ancestral U genome. The phylogenetic pattern of U genome based on ITS sequences also supported the "pivotal-differential" hypothesis. PMID- 11206850 TI - Computer simulation analysis suggests weak balancing selection operative at the MICA locus. AB - A high degree of polymorphism has been reported at the major histocompatibility class I chain-related gene A (MICA) locus, which is located 46 kb away from HLA Bin the human major histocompatibility complex (MHC) class I region. Although it is known that the polymorphisms at the conventional MHC class I loci have been maintained by balancing selection, it is unclear whether positive natural selection is also operative in maintaining the polymorphism at the MICA locus. In order to explain the degree of polymorphism at the MICA locus, a computer simulation study was carried out. The high degree of polymorphism at the MICA locus (heterozygosity and number of polymorphic residues) could not be explained solely by balancing selection at the HLA-B locus even if no recombination was assumed between MICA and HLA-B. Although there is no definite evidence indicating that balancing selection is operative at the MICA locus, our results suggest that the MICA gene is subject to weak balancing selection. PMID- 11206851 TI - Trait diversity, heritability and genetic advance in selected germplasm lines of tef. AB - The genetic improvement of the Ethiopian cereal, tef, Eragrostis tef (Zucc.) Trotter, depends upon the variability in the indigenous germplasm. A bi replicated randomized complete block field experiment was, therefore, carried out at Debre Zeit and Alem Tena in Ethiopia during the 1996 main season to study the pheno-morphic and agronomic trait diversity in 320 tef germplasm lines. All of the 17 traits assessed showed substantial (p < or = 0.001) variation among the lines. Genotypes and locations interacted significantly (p < or = 0.05) on 11 of the traits. At about 50% similarity level, the tef lines grouped into six major clusters of nine to 243 lines. Five principal components (PCs) extracted about 71% of the entire variation of the lines. About 28% of the total variance explained by the first PC was due chiefly to variation in main shoot culm length, diameters of the two basal culm internodes, panicle length and grain yield/panicle. About 16% of the whole variance explained by the second PC originated mainly from variation in the length of the first and second basal culm internodes, grain yield/plant, and peduncle length. The third PC accounting for about 12% of the entire variance resulted largely from variation in harvest index and shoot phytomass yield/plant. Across traits, the phenotypic and genotypic coefficients of variation varied in that order from about 2% for grain yield/panicle to 58% for number of fertile tillers/plant, and from less than 1% for diameters of the two basal culm internodes and grain yield/panicle to 35% for panicle length. Estimates of broad sense heritability and genetic advance (as ratio of the mean) were highest for panicle length (71%) and number of fertile tillers/plant (21%), respectively. But both of these were lowest for the second basal culm internode diameter (< 1%). Overall, the study confirmed that tef is a highly versatile crop with broad trait diversity in the germplasm, and this offers ample opportunities for improvement through breeding. PMID- 11206852 TI - Nucleotide sequence of 5S rDNA and localization of the ribosomal RNA genes to metaphase chromosomes of the Tilapiine cichlid fish, Oreochromis niloticus. AB - In this study, we report the cloning and nucleotide sequence of PCR-generated 5S rDNA from the Tilapiine cichlid fish, Oreochromis niloticus. Two types of 5S rDNA were detected that differed by insertions and/or deletions and base substitutions within the non-transcribed spacer (NTS). Two 5S rDNA loci were observed by fluorescent in situ hybridization (FISH) in metaphase spreads of tilapia chromosomes. FISH using an 18S rDNA probe and silver nitrate sequential staining of 5S-FISH slides showed three 18S rDNA loci that are not syntenic to the 5S rDNA loci. PMID- 11206853 TI - Genetic erosion in northern marginal population of the common wild rice Oryza rufipogon Griff. and its conservation, revealed by the change of population genetic structure. AB - In order to monitor genetic erosion within the northern marginal population of common wild rice Oryza rufipogon Griff. from Dongxiang, Jiangxi Province, China, allozyme diversity encoded by 22 loci was analyzed electrophoretically from all the existing subpopulations in 1980, 1985 and 1994. The sample collected from the nine large subpopulations in 1980 showed the highest levels of genetic diversity (A = 1.27, P = 18.20%, Ho = 0.042 and He = 0.049) and a slight deviation from Hardy-Weinberg expectation (F = 0.143), the sample from five moderate ones in 1985 displayed medium levels of genetic diversity (A = 1.14, P = 13.60%, Ho = 0.008 and He = 0.049) and a great deviation from Hardy-Weinberg expectation (F = 0.837), and the sample from two small ones in 1994 demonstrated the lowest levels of genetic diversity (A = 1.09, P = 9.10%, Ho = 0.000 and He = 0.043) and the largest deviation from Hardy-Weinberg expectation (F = 1.000). The results not only documented the genetic erosion stemmed from the extinction of the subpopulations, but also revealed the drastic change of the population genetic structure due to the reduction of the population. Finally, some conservation strategies for the population are proposed. PMID- 11206854 TI - A new karyotype in Callicebus torquatus (Cebidae, Primates). AB - We describe a new karyotype of Callicebus torquatus using conventional staining, G-banding with Wright Stain, CBG, Ag-NOR staining and fluorescence in situ hybridization (FISH) with human telomere probes and comparative analysis with the previously reported karyotype of C. torquatus torquatus (2n = 20). We studied a female specimen maintained in captivity at the Centro Nacional de Primatas (Para, Brazil). This titi monkey presented 2n = 22, with four large biarmed and six acrocentric autosome pairs; the X chromosome is a medium submetacentric. C-bands were revealed at the centromeric region of all acrocentrics and X chromosome; punctual C-bands also are visualized at the centromeric region in the large biarmed pairs. The NOR site was located at the long arm of pair 4, at the position of a conspicuous secondary constriction. Hybridization signals were detected exclusively at the terminal region of all chromosomes. The karyotype described here has one acrocentric pair more than that found in the literature and also differs by amount and distribution of constitutive heterochromatin. Our data support the notion that the torquatus group may be composed of distinct species, each with its own karyotype. PMID- 11206855 TI - Half-sib analysis of three morphological traits in Drosophila melanogaster under poor nutrition. AB - Variation in thorax length, wing length and sternopleural bristle number was examined in Drosophila melanogaster reared in stressful and nonstressful environments using paternal half-sib design. Low concentration of yeast in the medium was used as a stress factor. Phenotypic variation of thorax length and wing length was higher under poor nutrition than in the control; in bristle number, phenotypic variation was relatively stable regardless of the environment. Heritability of all the traits analyzed was generally lower under nutritional stress. Heritability changes in thorax length and wing length were mainly due to an increase in the environmental variance under stress, whereas in bristle number, stress resulted in a decrease in genetic variation. Genetic variance in thorax length was higher under poor nutrition; in wing length, no difference in genetic variance between environments was found. PMID- 11206856 TI - Colonization of America by Drosophila subobscura: spatial and temporal lethal gene allelism. AB - About twenty years ago Drosophila subobscura, a western Palearctic species, colonized both North and South America. Lethal genes in the O chromosome has been subject to much research. Lethal gene allelisms between American populations far away have been studied. These allelisms were not negligible, but all cases were due to the lethal gene completely associated to the O5 chromosomal inversion. Here we analyze the lethal genes in a new American population of D. subobscura (Centralia, Washington), located fairly close to a previously studied population (Bellingham, Washington) and separated in space and time with other American populations (Gilroy I and II in California and Santiago de Chile). The frequencies of lethal and semilethal genes of Centralia were 16.9+/-4.6 and 6.2+/ 3.0, respectively. The intrapopulational allelism of Centralia was 0.122+/-0.036. Interpopulational allelisms were studied using the lethal genes from the populations separated in space and time from Centralia. The interpopulational allelisms between Centralia and Gilroy I (California) and between Centralia and Bellingham (Washington) were higher than the intrapopulational allelism (0.155+/ 0.032 and 0.153+/-0.024, respectively). In all these cases allelism was due to a complete association between a lethal gene and the O5 chromosomal inversion. Accordingly, no other lethal genes are shared in these populations. PMID- 11206857 TI - Synaptomenal complex analysis of four breeds of Bos taurus taurus x B. taurus indicus hybrids. AB - The synaptonemal complex (SC) was analyzed in four F1 hybrids of Bos taurus taurus and B. taurus indicus including Gyr-Simmental (G-S), Nelore Simmental (N S), Gyr-Holstein-Friesian (G-H) and Nelore-Piemontese (N-P). We analysed the frequency of various types of SC abnormalities and the frequency of cells with SC abnormalities. The results were compared with similar observations made on purebred animals. All the animals studied possessed 29 autosomal and one sex bivalent. The frequency of cells with abnormalities in the hybrids were 28.0% in the N-P, 29.1% in the G-S, 33.3% in the N-S and 40.0% in the G-H. The frequency of cells with abnormalities in the four hybrids was 31.5%; 57.9% of these abnormalities occurred in zygotene and 42.0% occurred in pachytene. The comparisons among the hybrids and among the hybrids and their parental breeds showed that the only significant difference was between Gyr and Gyr-Holstein Friesian animals. Some aspects of the relationship between the frequency of cells with anomalies and the fertility of hybrids are discussed. PMID- 11206858 TI - A phylogeny of the Drosophilidae using the sex-behaviour gene fruitless. PMID- 11206860 TI - The challenge of evidence-based migraine therapy. AB - It is important that physicians practise evidence-based medicine. Clinical experience is important, but there are a number of reasons why clinical experience can lead to the impression that ineffective treatments are effective. There are major educational and research challenges which must be met before clinicians can practice evidence-based migraine therapy more extensively than at present. Treating physicians will need to learn more about the principles of evidence-based medicine. Researchers will need to produce more and better clinical trials that address important clinical questions. The results of these trials will need to be reported clearly, and we need to improve the efficiency with which these results can be accessed. It is important that the pharmaceutical industry, clinicians, and academic health centres work together to meet these challenges. PMID- 11206859 TI - Nuclear DNA restriction site polymorphisms and the phylogeny and population structure of an intertidal snail species complex (Littorina). AB - Primers for amplification of four novel, unlinked nuclear DNA loci, the first reported for the rough periwinkles of the genus Littorina, are described. Patterns of restriction site polymorphism for these loci are detailed within the rough periwinkles. RFLPs are not found to be diagnostic for any of the currently accepted species within this group, nor for any of the contentious subspecies, or forms, whose taxonomic status is uncertain. However, there are important differences in allele frequencies between these taxa and certain of these mirror differences detected in a previous study of the mitochondrial DNA. These allele frequency data are used to construct a phylogeny in which groupings of the three recognised species are obvious when either Nei's genetic distances or Reynold's distances are clustered. Contentious forms (L. neglecta, L. saxatilis 'b' and L. tenebrosa) do not cluster as distinct taxa, although populations of L. neglecta have important allele frequency differences from L. saxatilis. These four loci have confirmed the consensus view of Littorina phylogeny and provided important information on population structure-however four loci is insufficient for reaching definitive conclusions. Since analysis of nuclear DNA polymorphisms such as these is invaluable for analysis of phylogeny, population structure and phylogeography, identification of additional loci is considered imperative. PMID- 11206861 TI - The principles of evidence-based medicine. AB - Evidence-based medicine (EBM) integrates individual clinical expertise with the best available external evidence in the care of individual patients. By enabling clinicians to directly appraise and apply current clinical research, EBM deals with the problems of deterioration in clinical performance, information overload, and lag in application of research findings to clinical practice. Thus, EBM is a useful tool to address the problems faced by clinicians attempting to provide optimum, current care for their patients. The rationale for EBM, its principles and application, as well as some limitations, are described here. PMID- 11206862 TI - Acute migraine treatment outcome measures: a clinician's view. AB - The efficacy of acute therapies for migraine can be measured in many ways. Traditional endpoints (such as reduction in pain from moderate or severe to mild or absent) are used for regulatory purposes, but do not reflect all components of the migraine syndrome, nor, necessarily, what is most valued by patients and clinicians. There is also a pharmacokinetic-pharmacodynamic disconnection for these traditional types of endpoint, suggesting that they teach us little about how these drugs work. More rigorous, but nonetheless pain-score based, endpoints are reviewed. The biases that can attach to measures such as therapeutic gain and number needed to treat, in the context of migraine therapy, and the limitations of these measures for use in meta-analysis, are discussed. The clinical subtleties of these endpoints are numerous: understanding patients' ability to distinguish between multiple headache types, the best timing of treatment relative to the start of an attack, and measuring clinical outcome may be statistically difficult, but yet may also provide more clinical utility than pain score analyses. The three therapeutic strategies (Step, Stepped-within-attack, and Stratified care) are reviewed and the place of 5HT(1B/1D) agonists within them, based on the currently best available evidence, is identified. Consideration should be given to more real-life studies, to measuring drug efficacy after early administration during onset of headache, and to greater sophistication in our approach to the necessarily gestalt measures of patient satisfaction and treatment preference. PMID- 11206863 TI - Drug comparisons: why are they so difficult? AB - Comparing therapeutic agents in a drug class can be difficult. This article examines the ways in which the triptans can be and have been compared and evaluates the advantages and disadvantages of the approaches. Direct comparative trials are clearly the best method for evaluating the triptans, however, there is a scarcity of this type of data on the currently available compounds. Indirect comparison such as meta-analysis is a second method of comparing these agents but only serves as an estimate of relative efficacy or safety based on a comparison of pooled data derived from a number of different trials for each agent. Comparison of the data found in the regulatory documents represents another type of indirect comparison that can be done so long as the data is presented in a consistent format across products. PMID- 11206864 TI - Evidence-based analysis of a migraine treatment drug comparison trial. AB - Patients present with specific problems against a background of their particular situation. The applicability of a treatment to a specific case may be difficult to assess in the light of the information available on that treatment. Evidence based medicine is a discipline developed to achieve the best informed treatment decisions in clinical situations. In this paper, we illustrate a logical approach to reaching a decision regarding which of two migraine treatments should be used in a clearly defined patient. The information evaluated is a comparative trial between sumatriptan (100 mg), rizatriptan (5 and 10 mg) and placebo. The use of the analytical tools of evidence-based medicine is demonstrated in this exercise. The example was chosen because this is an area of great current interest in the field of neurology. PMID- 11206865 TI - Evidence-based migraine therapy: learning needs and knowledge assessment. AB - One of the primary goals of continuing medical education (CME) is to enhance the learners' performance, and a major goal of evidence-based medicine (EBM) is to improve knowledge of current best care. This paper overviews the use of a Learning Needs and Knowledge Assessment tool to highlight the potential learning needs and knowledge of neurologists and to focus the issues, interest and interactions of neurologists in a workshop on EBM migraine therapy. Virtually all neurologists felt they used evidence-based medicine in their daily practice. Surprisingly, 50% of neurologists agreed that they were uncertain which triptan to use. The great majority of neurologists felt that the triptans were not all equally efficacious. Our survey identified significant knowledge gaps among neurologists regarding how to appraise the validity of evidence from a randomized clinical trial, and with regard to what are the most clinically useful measures of benefit in clinical trials. PMID- 11206866 TI - Hepatitis G virus infection in India: prevalence and phylogenetic analysis based on 5' non-coding region. AB - OBJECTIVES: To determine the prevalence of hepatitis G virus (HGV) infection in western India and to carry out phylogenetic analysis of HGV isolates. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) assay was used to detect HGV RNA in serum samples obtained from paid plasma donors, patients with hemophilia and voluntary blood donors. Nine Indian and one Kenyan HGV RNA positive samples were sequenced in the 5' non-coding region (5'-NCR). Phylogenetic analysis based on the comparison of a 101 nucleotide fragment from a large number of HGV isolates from 22 countries (including Indian and Kenyan sequences obtained during the present study) was carried out. RESULTS: HGV RNA positivity rates among paid plasma donors from a commercial plasmapheresis unit (7/43, 16.3%) and patients with hemophilia (5/44, 11.4%) were significantly higher than that in voluntary blood donors (0/51; p=0.003 and 0.019, respectively). Among patients with acute non-A to E hepatitis and fulminant hepatic failure, 1 of 50 and 1 of 28 were HGV RNA-positive, whereas 6 of 49 (12%) patients with chronic liver disease had circulating HGV RNA. All Indian isolates belonged to genotype 2, whereas the Kenyan isolate formed a distinct branch within genotype 1 consisting of African isolates. CONCLUSION: Our results suggest existence of parenteral transmission of HGV in the Indian population. HGV was not an important cause of acute non-A to E hepatitis or fulminant hepatic failure among the patients investigated. Genotype 2 seems to be the most prevalent genotype in western India. PMID- 11206867 TI - Effect of rotavirus infection on lipid composition and glucose uptake in infant mouse intestine. AB - OBJECTIVE: To study the effect of rotavirus infection on lipid composition and glucose uptake in small intestine of infant mice. METHODS: Thirty six 7-day old balb/c mice were given 50 mL (100 ID50) rotavirus suspension orally; 36 control animals received only normal saline. Body weight of animals was recorded. Six animals in each group were sacrificed on days 0, 1, 3, 5, 7 and 10 post inoculation (pi). Intestines were removed, everted and homogenized in ice-cold saline. Cholesterol and phospholipid content, glucose uptake and alkaline phosphatase in the jejunum and ileum were determined. RESULTS: Rotavirus infection led to a significant decrease in body weight with on days 3 and 5 pi as compared to controls, and to an increase in cholesterol and phospholipid content of the intestine. Uptake of glucose also increased significantly. Alkaline phosphatase activity was significantly reduced on days 3 and 5 pi as compared to controls. CONCLUSION: This study provides characterization of the lipid composition and uptake of glucose in infant mice small intestinal segments during rotavirus infection. PMID- 11206868 TI - Gastroenterology on the internet--V. PMID- 11206869 TI - Intrapulmonary vascular dilatation in portal hypertension due to cirrhosis of liver. AB - BACKGROUND: Intrapulmonary vascular dilatation in patients with portal hypertension due to chronic liver disease has been reported mainly from Western countries. METHODS: Fifty in-patients with portal hypertension due to cirrhosis of the liver were subjected to contrast-enhanced two-dimensional echocardiography in order to detect the presence of intrapulmonary vascular dilatation. Their arterial blood oxygen saturation was measured. The patients, including 37 men, were aged mean 43.5 years; 30 had alcoholic cirrhosis and 20 postnecrotic cirrhosis. Twelve patients were in Child-Pugh, class B and 38 in class C. RESULTS: None of the 50 patients was cyanosed or had clubbing. Their mean pO2 was 83.2 mmHg. None had evidence of intrapulmonary vascular dilatations. CONCLUSION: Intrapulmonary vascular dilatation was not observed in our patients with liver cirrhosis. However, the sensitivity of contrast-enhanced echocardiography for this purpose needs to be reviewed. PMID- 11206870 TI - Hepatopulmonary syndrome: prevalence and clinical profile. AB - BACKGROUND: The hepatopulmonary syndrome (HPS) is defined as a triad of liver dysfunction, intrapulmonary vascular dilatations (IPVD) and arterial hypoxemia. There is paucity of Indian studies regarding the prevalence of IPVD and arterial hypoxemia particularly amongst patients with non-cirrhotic portal fibrosis (NCPF) and extrahepatic portal vein obstruction (EHPVO), where liver dysfunction is not a feature. METHODS: All patients with portal hypertension and esophageal varices seen at a tertiary care hospital during 1995-98 were studied. Ultrasonography of abdomen, contrast-enhanced echocardiography (CEE), arterial blood gas analysis and assessment of alveolar-arterial oxygen gradient were done. RESULTS: Of 138 patients with portal hypertension seen during the study period, 88 fulfilled the inclusion and exclusion criteria. These included 63 with cirrhosis, 15 with NCPF and 10 with EHPVO. CEE showed IPVD in 17 (27%) patients with cirrhosis, of which 11 (17.5%) fulfilled the criteria for HPS. IPVD were also noted in 4 (26.6%) cases of NCPF and 3 (30%) of EHPVO, though only 2 (13.3%) and 1 (10%) respectively had elevated alveolar-arterial gradient and liver dysfunction in addition. Age and sex distribution and duration of symptoms were not different in patients with HPS. Patients with HPS had higher incidence of dyspnea, platypnea, clubbing and spider nevi. CONCLUSIONS: Hepatopulmonary syndrome is present in 17.5% of cirrhotics, 13.3% of patients with NCPF and 10% with EHPVO. Patients with HPS had significantly higher incidence of dyspnea, platypnea, clubbing and spider nevi. PMID- 11206871 TI - Primary biliary cirrhosis: an Indian experience. AB - Primary biliary cirrhosis (PBC) is believed to be rare in India. We analyzed our data pertaining to patients with PBC seen in a tertiary referral center over a 5 year period. The diagnosis of PBC was based on liver biochemistry, histology and antimitochondrial antibodies, in the absence of biliary obstruction. Five patients, all women, were diagnosed to have PBC. Pruritus, jaundice and fatigue were the most common initial symptoms. Hepatomegaly was seen in 4 of 5 patients. Associated autoimmune diseases were present in 2 patients. All patients presented with mild hyperbilirubinemia (< or = 6 mg/dL) with disproportionately raised serum alkaline phosphatase level. AMA was positive in 4 patients. Liver biopsy showed stage III-IV disease in 3 of 4 patients. The clinical presentation and course of PBC in India are similar to the experience in the West. PMID- 11206872 TI - Hepatopulmonary or portopulmonary syndrome? PMID- 11206873 TI - Dermatofibrosarcoma protuberans of the jejunum. AB - We report a 55-year-old man with recurrent bleeding from the small intestine. Preoperative investigations suggested it to be a small intestine tumor. The resected specimen was diagnosed at histology as dermatofibrosarcoma protuberans of the small bowel. PMID- 11206874 TI - Leiomyosarcoma of third part of duodenum with perforation. AB - Malignant stromal cell tumors of the duodenum present with pain or bleed. We report a patient with leiomyosarcoma of the third part of the duodenum that presented with perforation. PMID- 11206875 TI - Ganglioneuroma of small intestine presenting with perforation peritonitis. AB - We report a 42-year-old man with benign solitary small intestinal ganglioneuroma presenting with perforation peritonitis. The patient had no evidence of MEN IIB syndrome. Simple segmental resection was done; the patient is well on follow up one year later. PMID- 11206876 TI - Laparoscopic cholecystectomy in patient with portal cavernoma and portal hypertension. AB - Successful laparoscopic cholecystectomy has been reported in patients with cirrhosis of liver with portal hypertension; the procedure has, however, not been reported in patients with portal vein thrombosis, portal cavernoma and portal hypertension. We report an 18-year-old man with portal hypertension due to portal vein thrombosis and portal cavernoma who had symptomatic gallstone disease and was successfully treated with laparoscopic cholecystectomy. PMID- 11206877 TI - Leiomyosarcoma of inferior vein cava presenting as acute Budd-Chiari syndrome. AB - We report a 49-year-old lady who presented with acute Budd-Chiari syndrome. Spiral CT scan showed inferior vein cava (IVC) tumor and ischemia of the right liver secondary to hepatic vein blockage. These were confirmed by MRI scan and IVC gram, at which time tissue diagnosis was obtained. At surgery, the tumor was seen to originate from the infrahepatic IVC and extended to the level of the diaphragm, blocking the hepatic vein outflow. The tumor was excised completely. Histology confirmed it to be leiomyosarcoma of the IVC. The patient is well, without recurrence of symptoms or tumor, 10 months later. PMID- 11206878 TI - Mesothelial cyst at porta hepatis. AB - Mesothelial cysts are fluid-filled sacs lined by mesothelial cells. They are rare lesions that have been known to occur at various sites, but have not been reported at the porta hepatis. We report a 45-year-old woman with mesothelial cyst at the porta hepatis that was detected incidentally during open cholecystectomy. PMID- 11206879 TI - Implantation malignancy after laparoscopic cholecystectomy. AB - Laparoscopic cholecystectomy may result in spillage of gall bladder contents during dissection or delivery of gall bladder through the umbilical port. We report a 50-year-old man who underwent laparoscopic cholecystectomy for suspected calculous cholecystitis. Histology showed a single focus of adenocarcinoma in the gall bladder. There was spillage of gall bladder contents at the umbilical port during delivery. Six months later, he developed adenocarcinoma at the port site. This was treated by wide excision. PMID- 11206880 TI - Eradication of Helicobacter pylori with a metronidazole-containing regimen in a metronidazole-abusing population. PMID- 11206881 TI - Ulcerative colitis in a married couple. PMID- 11206882 TI - Neonatal ectopic pancreatic cyst. PMID- 11206883 TI - Self-reported disease awareness--a questionnaire survey of ulcerative colitis patients. AB - OBJECTIVE: To evaluate patient knowledge about ulcerative colitis and relate this to their socio-demographic characteristics. METHODS: 145 patients with ulcerative colitis were given a two-sectioned awareness questionnaire in a language they understood. The first section, which tested disease awareness, consisted of 16 items. Awareness was classified as very low (< or = 4 correct answers), low (5 8), medium (9-12) and high (13-16). The second section contained 11 questions pertaining to general opinions and views about the disease. RESULTS: Nine (6.2%) participants had very low level of awareness, 107 (73.8%) low level, 29 (20%) medium, and none high disease awareness. Only disease duration influenced disease awareness significantly. Age, sex, marital status, occupation and education level had no relation to the level of awareness. A majority of patients resorted to use of alternative medicines during their disease course; however, with increasing awareness the use of other types of therapy was reduced. Drug compliance had significant association with disease awareness. CONCLUSIONS: Our patients with ulcerative colitis had poor disease awareness. Since awareness affected treatment compliance, the study emphasizes the need for better education of the patients and their family about the disease. PMID- 11206884 TI - Symptomatic, endoscopic and histological assessment of upper gastrointestinal tract in renal transplant recipients. AB - AIM: To assess the prevalence of gastrointestinal symptoms, endoscopic findings, and histological abnormalities in renal transplant recipients. SETTING: Teaching hospital in northern Jordan. METHODS: Seventy-six renal transplant recipients with stable renal function were interviewed for gastrointestinal symptoms, and underwent upper gastrointestinal endoscopy; gastric antral biopsies were evaluated for inflammatory changes and the presence of Helicobacter pylori. One hundred consecutive patients attending the general medical outpatient for various medical problems served as controls; 41 of them consented to undergo endoscopy and biopsy examination. RESULTS: Upper gastrointestinal symptoms were present in 50% of patients compared to 47% of controls (p=0.80). Endoscopic abnormalities were found in 71% versus 63.4%. One patient in each group had duodenal ulcer. H. pylori were found in 60.5% versus 46.3% (p=0.20), and histological gastritis in 40 (52.6%) with acute inflammatory changes in 22 (28.9%), compared to 21 (51.2%) and 15 (36.6%) controls, respectively. Monilial and cytomegalovirus esophagitis were found in 2 (2.6%) and one patient, respectively. CONCLUSIONS: Prevalence of gastrointestinal symptoms and endoscopic and histological findings in stable renal transplant recipients are similar to those in controls. Also, there was no increase in opportunistic infections of the gastrointestinal tract or of gastric H. pylori in these patients. PMID- 11206885 TI - Carotid endarterectomy based on duplex ultrasound in patients with and without hemispheric symptoms. AB - Carotid endarterectomy is the most commonly performed vascular procedure. This retrospective study was conducted to determine the efficacy of duplex imaging as the sole diagnostic study for preoperative evaluation of symptomatic and asymptomatic patients who underwent carotid endarterectomy. We conducted a retrospective case series analysis in a community teaching hospital. From January 1994 to September 1998, 316 patients underwent carotid endarterectomy for carotid stenosis. A total of 177 patients were symptomatic and 139 patients were asymptomatic. Angiography was performed routinely in the beginning of the study but later was performed only in selected patients. Preoperative duplex ultrasound of carotid artery was performed by a laboratory accredited by the Intersocietal Commission for the Accreditation of Vascular Laboratories. Data were reviewed to obtain morbidity and mortality rates, and duplex imaging results were compared with operative findings. Cost and risk analysis of carotid angiography reviewed. This study reviewed variables of age, sex, race, diabetes, smoking, hypertension, hypercholesterolemia, coronary artery disease, and renal failure. Five patients had a lesion in the proximal portion of the carotid artery by duplex imaging criteria. Duplex ultrasound results were grossly confirmed intraoperatively in all patients except in one patient who was found to have complete occlusion of carotid artery whose duplex was read as high-grade stenosis. The duration of stay ranged from two to 30 days. This duration was influenced by patients' comorbid conditions, postoperative complications or simultaneous coronary artery bypass graft. Four patients had a stroke within 30 days of surgery making the stroke rate of 1.26 per cent. There has been considerable debate on the use of duplex ultrasound as the only method of preoperative evaluation of carotid stenosis before carotid endarterectomy. Our study demonstrates that it is safe to perform carotid endarterectomy based on neurologic history and duplex ultrasound with good technical quality performed in an accredited vascular laboratory. This approach eliminates the cost and risk associated with angiography. Proximal carotid and intrathoracic lesions are rare and can be predicted by the duplex study. We think that carotid angiography is required only when duplex imaging is suboptimal or equivocal in the presence of atypical symptoms or uncommon vascular abnormalities. PMID- 11206886 TI - Leonardo da Vinci: anatomist and physiologist. PMID- 11206887 TI - Surgery by the lowest bidder? PMID- 11206888 TI - Mirizzi's syndrome: experience from a multi-institutional review. AB - P.L. Mirizzi described in 1948 a partial or spastic obstruction of the common hepatic duct secondary to an impacted gallstone in the cystic duct or infundibulum of the gallbladder. The modern definition of Mirizzi's syndrome is thought to include four components: anatomic arrangement of the cystic duct at the gallbladder neck such that it runs parallel to the common hepatic duct; impaction of a stone in the cystic duct or neck of the gallbladder; mechanical obstruction of the common hepatic duct by the stone itself or by secondary inflammation; and intermittent or constant jaundice causing possible recurrent cholangitis and, if longstanding, secondary biliary cirrhosis. Intermittent symptomatology may make Mirizzi's syndrome difficult to diagnose preoperatively or intraoperatively. Bilio-biliary fistulas may or may not be present. Diagnosis and choice of operative repair may be best accomplished by open operative technique. Over a 24-year period two faculty members from Louisiana State University (LSU) Medical Center-Shreveport at Monroe and LSU Baton Rouge treated 4180 cases of cholelithiasis at six Louisiana university and private hospitals. Eleven cases of Mirizzi's syndrome were diagnosed on the basis of operative and preoperative notes with detailed description of size and extent of biliobiliary fistulas when they were present. These 11 cases were reviewed and followed from one to 20 years. Presentation, workup, operative findings, choice of operative repair, choice of operative approach, and complications were evaluated by retrospective chart review. Review of the pertinent literature for informative and comparative purposes was also completed. These 11 cases ranged from Csendes Type I to III. There were no Type IV cases. They were ultimately diagnosed and managed by classical open technique. Four laparoscopic procedures were converted to open technique following initial inspection. All four were converted to open as a result of inability to delineate structures in and adjacent to the triangle of Calot due to marked scarring in the subhepatic space. No iatrogenic injuries or major complications occurred. Mirizzi's syndrome occurs in fewer than 0.5 per cent of patients with cholelithiasis. Removal of stones with partial cholecystectomy and use of gallbladder or cystic duct remnant to oversew or repair Mirizzi fistulas should be considered. Roux-en-y hepaticojejunostomy becomes the procedure of choice when the vascularity or viability of the hepatic duct or tissues available for duct repair is questionable. Review of the literature reveals the increase in complications with laparoscopic versus open technique in Mirizzi's syndrome. Although very little direct evidence exists we believe that when this syndrome is diagnosed or strongly suspected open biliary operation is the procedure of choice because the increased potential for major complications with the use of laparoscopic technique far outweighs the potential slight increase in morbidity of an open procedure. PMID- 11206889 TI - Effect of a composite membrane of chitosan and poloxamer gel on postoperative adhesive interactions. AB - Excessive postoperative adhesion formation is a major result of surgery. The adhesion reduction effects of a chitosan membrane and poloxamer gel barrier were measured in a rat peritoneal model. Forty-four male Sprague-Dawley rats were divided into four groups (control, poloxamer, chitosan, and poloxamer+chitosan sandwich). Two cm2 of cecal serosa and the adjacent abdominal wall were abraded. The denuded cecum was covered with either a chitosan membrane, a poloxamer gel, chitosan in a sandwich configuration with poloxamer on both sides, or neither (control group) and apposed to the abdominal wall. Fourteen days after surgery adhesions were graded using a whole-number scoring system of zero to five. Adhesion strength was determined using a whole-number system of one to four. Adhesion area was measured on a continuous scale of adhesion severity. Adhesion grades were highest in the control group (5.00 +/- 0.00) and were significantly (P < 0.05) lower in the poloxamer group (3.50 +/- 1.35), the chitosan group (1.64 +/- 1.63), and the poloxamer+chitosan group (1.18 +/- 1.25). The two chitosan containing groups also had significantly (P < 0.05) reduced adhesion grades in comparison with the poloxamer group. Adhesion area in both chitosan-containing groups was reduced in comparison with control and adhesion strength was reduced significantly (P < 0.05) in all groups compared with control. The poloxamer+chitosan group had significantly (P < 0.05) reduced adhesion strength versus poloxamer only. There was a significant (P < 0.05) linear correlation (r = 0.931, P < 0.001) between adhesion grade and adhesion strength. We conclude that chitosan and the combination of poloxamer+chitosan were shown to effectively reduce adhesion area, grade, and strength. PMID- 11206890 TI - The role of follow-up radiographic studies in nonoperative management of spleen trauma. AB - The management of splenic injuries has evolved significantly in recent years from an operative to a nonoperative approach in stable patients with blunt abdominal trauma. The management of these patients with serial radiographic studies before hospital discharge remains controversial. We reviewed the management of 90 patients retrospectively who were admitted to our Level II trauma center with splenic injuries secondary to blunt trauma to determine the value of serial radiographic studies. Forty-seven (52%) patients underwent immediate laparotomy. Forty-three (48%) patients were managed conservatively without surgery. All nonoperative patients had an initial CT of the abdomen to evaluate their abdominal injuries. Among the 43 patients managed without surgery 31 had no follow-up radiographic studies. Twelve patients had follow-up studies before discharge. Two of these 12 patients subsequently underwent splenectomy. Both had developed hypotension, tachycardia, and a decreasing hematocrit, which prompted their repeat radiographic studies. Ten patients had no change in their clinical status and showed no significant change in the radiographic injury pattern to the spleen. One patient who was initially managed nonoperatively became hemodynamically unstable with increasing abdominal pain and subsequently underwent splenectomy without follow-up radiographic studies. The remaining 30 patients who had no follow-up studies had no significant change in their clinical abdominal examinations and had no further complications from their splenic injuries. Routine follow-up radiographic evaluations are not necessary in the nonoperative management of stable patients with splenic injuries. PMID- 11206891 TI - Routine chest X-rays after insertion of implantable long-term venous catheters: necessary or not? AB - Can long-term subcutaneous venous (Mediport) catheters be safely inserted without routine chest X-ray (CXR) verification? An estimated 500,000 Mediport catheters are inserted yearly in the United States, and elimination of unnecessary radiographs would result in substantial savings of increasingly limited health care resources. A total of 513 consecutive Mediport catheters were inserted by a single surgeon over a 5-year period using a standardized protocol and selective indications for follow-up CXR that included unilateral chest pain, aspiration of air, decreased breath sounds, and difficult catheter insertion. The 513 catheters were inserted in 498 patients with 271 patients (53%) undergoing postprocedure CXR. Of the 513 catheters 461 (90%) were placed by percutaneous approach to the subclavian vein. Six pneumothoraces (1.2% incidence) occurred, all in patients who met criteria for immediate CXR. The overall complication rate was 3.1 per cent and included eight instances of catheter-tip malposition (seven of the eight were successfully repositioned by vascular radiology), one mediastinal hematoma, and one chest-wall hematoma. This largest single-surgeon-reported series demonstrates that Mediport insertion can be safely accomplished with minimal complications following a standardized protocol using selective radiologic evaluation. PMID- 11206892 TI - Diaphragmatic hernia after Ivor-Lewis esophagectomy manifested as lower gastrointestinal bleeding. AB - Diaphragmatic hernia after esophageal resection is a recognized but rare complication. Parahiatal hernias may result from manipulation and extension of the crura during surgery. This can lead to a wide array of symptoms depending on the extent and organ that is herniated. A high index of suspicion is required because there is no one symptom that is specific for herniation. This report represents the first case of a patient presenting with lower gastrointestinal bleed from a parahiatal hernia after esophageal resection. PMID- 11206893 TI - Gingko biloba: a case report of herbal medicine and bleeding postoperatively from a laparoscopic cholecystectomy. AB - An increasing variety of alternative health care products (defined as "over-the counter," nonprescribed herbal medicines) are taken by patients for a plethora of reasons. Unfortunately these self-prescribed remedies are seldom considered by the patient to be medications and as a result it has been noted that 70 per cent of patients do not reveal herbal use to their allopathic practitioners or hospital personnel. The rapid growth of this herbal self-therapy has important implications for the practice of surgery. A case of post-laparoscopic cholecystectomy bleeding in a patient taking Gingko biloba is reported. This preparation has been reported to cause spontaneous bleeding and may interact with anticoagulants and antiplatelet agents. Other herbal medicines have also been associated with potential increased bleeding including garlic, feverfew, ginger, and ginseng. It is vital for surgeons to be apprised of all substances ingested by patients, to be cognizant of their potential adverse effects and drug interactions, and to be familiar with their therapeutic modality, all of which will help to optimize therapeutic approaches and improve patient outcome. PMID- 11206894 TI - Surgical treatment of severe colonic inertia with restorative proctocolectomy. AB - Patients with severe constipation due to colonic inertia who remain symptomatic after extensive medical therapy or partial colonic resection have occasionally been treated with ileostomy as a last resort. The hospital records of five patients with persistent symptomatic idiopathic colonic inertia were reviewed. Each of the patients had undergone extensive medical management, and eventually four underwent one or more colonic resections to relieve the recurrent abdominal distention and pain. Three of the patients eventually received a distal ileostomy, which functioned well. Anorectal manometric studies were within normal range for each of the five patients. Restorative proctocolectomy (J pouch) was therefore performed for each. With a mean follow-up of 42 months after restorative proctocolectomy each of the five patients was relieved of constipation and small bowel distention. The average number of bowel movements per 24 hours at 6 months was 4.8. All patients were able to discriminate flatus from stool, could hold back for up to 1.5 hours after the initial urge to defecate, and had total daytime continence. Each returned to work or school within 3 months, and each reported greater satisfaction with bowel function than with the ileostomy. Restorative proctocolectomy with a J pouch provides a satisfactory option for the management of patients with persistent abdominal distention and pain due to idiopathic colonic inertia. PMID- 11206896 TI - Does cell-saver blood administration and free hemoglobin load cause renal dysfunction? AB - Our aim was to evaluate the impact of cell-saver volume and free hemoglobin load on renal dysfunction. Intraoperative blood salvage was conducted in standard fashion, and in each case a sample of the blood was removed for testing. Outcome data on individual patients were collected during a 6-year period (1992-1998). The total amount of free hemoglobin each patient received was calculated. Renal dysfunction was defined as a rise in creatinine level of 1.0 mg/dL above baseline. There were a total of 125 patients who received salvaged blood. The free hemoglobin concentration ranged from 19 to 304 mg/dL (mean, 87.5 mg/dL). Patients were stratified into groups on the basis of the total free hemoglobin received, and the Kruskal-Wallis test demonstrated a difference between groups in the prevalence of renal dysfunction (P < 0.001). A total of 15 patients (12%) had significant postoperative renal dysfunction. There was an association between the amount of free hemoglobin load and subsequent renal dysfunction. This may warrant further study toward establishing policies and limits regarding maximal free hemoglobin blood. PMID- 11206895 TI - Meckel's diverticulum causing cecal volvulus. AB - Meckel's diverticulum is present in 2 per cent of the population with bowel obstruction as its most common complication. This case report describes an extremely rare complication of a Meckel's diverticulum, a cecal volvulus. The diagnosis of cecal volvulus was made preoperatively on abdominal X-rays; the diagnosis of a Meckel's diverticulum was made intraoperatively. The cecum was found to be twisted around a vitelline band on a broad-based Meckel's diverticulum extending to the umbilicus. The diverticulum was resected. The patient did well postoperatively and was discharged without any difficulty. PMID- 11206897 TI - The ascendance of laparoscopic splenectomy. AB - The application of laparoscopic techniques for abdominal procedures has been achieved with varying success. The general acceptance of laparoscopic splenectomy (LS) may be hindered by its infrequent performance and difficulty in manipulating the spleen. A retrospective review of splenectomies performed for primary splenic pathology was done to assess the role and outcome of LS. One hundred fifty LSs were performed from July 1995 through September 1999. Over that time period the proportion of LS performed increased steadily from 17 to 75 per cent of all splenectomies. The primary indications for splenectomy included immune thrombocytopenic purpura in 75 (50%), lymphoma/leukemia 36 (24%), and splenomegaly 19 (13%). There were 86 females and 64 males. Immediately before operation 36 patients (4%) had a platelet count <50,000/ mL, and 24 patients (16%) a hemoglobin <10 mg per cent. The mean operative time was 161 minutes with an average blood loss of 138 cm3 (<50-800). The mean morcellated weight of the entire group was 411 g (33-3300) indicating generally large splenic size. In the 37 patients with splenomegaly the mean weight was 735 g (293-3300). There were two conversions to open splenectomy. Two patients with hematologic malignancy, splenomegaly, and cytopenias died from overwhelming post-splenectomy sepsis (1.3%). Morbidity occurred in 14 (9%) with the most common complication being pancreatitis in seven (5%). The median length of postoperative stay was 2.4 days (range 1-5). In summary LS has rapidly replaced the open approach for nearly all elective splenectomies in adults and children. When performed with the patient in the lateral position it can be accomplished with minimal morbidity, even in complex patients, including those with splenomegaly. PMID- 11206898 TI - Comparison of safety and cost of percutaneous versus surgical tracheostomy. AB - Tracheostomy continues to be a standard procedure for the management of long-term ventilator-dependent patients. Traditionally the procedure has been performed by surgeons in the operating theater using an open technique. This routine practice has recently been challenged by the introduction of bedside percutaneous dilatational tracheostomy (PDT), which has been reported to be a cost-effective alternative. The purpose of this study is to evaluate and compare the safety, procedure time, cost, and utilization of percutaneous and surgical tracheostomies at a university hospital. A retrospective medical chart review was performed on all ventilator-dependent intensive care unit patients at the University of Virginia Medical Center undergoing tracheostomy during a 23-month period beginning December 26, 1996. Of the 213 patients identified for review, 74 and 139 patients received percutaneous and surgical tracheostomies, respectively. Of 74 percutaneous tracheostomies, 73 reviewed were performed by general surgeons, pulmonary physicians, or anesthesiologists in the intensive care unit; all open tracheostomies were performed by surgeons in the operating room, and one percutaneous procedure was performed in the operating room. Perioperative complications occurred in five of 74 patients (6.76%) during PDT; of these, three patients (4.1%) experienced major complications requiring emergent operative exploration of the neck. Three patients (2.2%) experienced perioperative complications during surgical tracheostomy. The mean procedure time was significantly shorter for the percutaneous procedure. Average charges per patient in an uncomplicated case including professional fees, inventory, bronchoscopy (if performed), and operating room charges were $1753.01 and $2604.00 for percutaneous and standard tracheostomies, respectively. These charges do not include the charges associated with surgical intervention after PDT complications. In contrast to previously published reports showing complications clustered during a physician's first 30 percutaneous cases, our study demonstrated no relationship between complication occurrence and physician experience. That is, no learning curve associated with performing PDT was evident. In addition there was no association seen between physician specialty and complication rate. PDT in the intensive care unit costs less than surgical tracheostomy performed in the operating room and can be performed in less time. Several other studies have recommended that bronchoscopy during PDT provides additional safety; however, in our series all three major complications took place during bronchoscopy-assisted percutaneous procedures. Our series suggests that PDT carries an appreciable risk of major complications. Careful patient selection and additional experience with the procedure may decrease complication rates to an acceptable level. PMID- 11206899 TI - Impact of presenting physiology and associated injuries on outcome following traumatic rupture of the thoracic aorta. AB - We hypothesized that the predominant factor influencing outcome of traumatic rupture of the thoracic aorta (TRA) was the degree of shock on presentation and associated injuries. We reviewed our experience with TRA over a 15-year period. Patients were classified as "unstable" if presenting systolic blood pressure was <90 mm Hg or if it decreased to <90 mm Hg after admission. We determined the presence of closed head injury, cardiac risk factors, a preoperative acute lung injury (ALI). The influence of these factors on mortality, postoperative adult respiratory distress syndrome (ARDS), and paralysis was analyzed. One hundred thirty-six patients were admitted with TRA. One hundred twenty underwent operative repair with a mortality of 31 per cent. Operative mortality was significantly higher in unstable patients (62%) versus stable patients (17%, P = 0.001), in patients with cardiac risk factors (71%) versus those without (24%, P = 0.001), and in patients with preoperative free rupture (83%) with versus those without (19%, P = 0.001). Free rupture was the cause of hypotension in only 10 of 42 unstable patients, with the remainder being due to other causes. Preoperative ALI was associated with a marked increase in postoperative ARDS (47% with vs 9% without, P = 0.001) but not operative mortality. Mechanical circulatory support (MCS) was used in 59 cases, none of whom experienced paralysis, whereas eight of 61 operated on without MCS developed paralysis (P = 0.001). When logistic regression was applied the use of MCS was not determined to be statistically significant. However, preoperative instability was found to be a significant predictor of postoperative paralysis with the risk being increased 5.5 times (confidence interval 3.3-10). The predominant factor influencing mortality, postoperative ARDS, and paralysis was preoperative instability and associated injuries. In patients who are hypotensive, other injuries should take precedence over repair of TRA. Patients who are stable but who have cardiac or pulmonary risk factors may be better managed by a period of nonoperative management until their condition improves. PMID- 11206900 TI - Evolving techniques in the treatment of carotid artery kinking: the use of resected redundant arterial segment. AB - Internal carotid artery kinking is frequently accompanied by atheromatous disease at the carotid bifurcation, and in this case both lesions may be treated simultaneously. Various surgical techniques have been used to correct carotid kinking but no particular one has been widely established. We conducted a retrospective review of 18 patients operated upon for internal carotid kinking during the last 5 years, which represents 4.1 per cent of the total carotid procedures performed during the same period. In 13 of the 18 patients carotid endarterectomy was performed before the repair of the kink. In four patients resection of the kinked segment with end-to-end anastomosis was performed combined with longitudinal arteriotomy at the carotid bifurcation. Two patients developed restenosis at the site of anastomosis requiring reoperation with patch angioplasty. Three patients were treated with eversion endarterectomy and end-to side anastomosis, whereas in six patients we performed resection of the redundant internal carotid artery combined with longitudinal arteriotomy at the bifurcation. The posterior wall was reconstructed with interrupted sutures and the procedure was completed with patch angioplasty of the anterior wall. In four of these cases we used the autogenous resected arterial segment as patch material. None of these patients developed restenosis or symptoms in a follow-up period of 3 to 32 months. In cases in which significant carotid artery stenosis and internal carotid kinking coexist resection of the involved segment with end to-end anastomosis of the posterior wall and patch angioplasty using the resected autogenous arterial segment constitute a convenient and satisfactory method of reconstruction. PMID- 11206901 TI - Porcelain gallbladder is not associated with gallbladder carcinoma. AB - The surgical management of porcelain gallbladder is based on studies performed in 1931 and 1962, which indicated a correlation between porcelain gallbladder and carcinoma. We sought to evaluate the characteristics of patients with porcelain gallbladder and the risk for gallbladder carcinoma. The medical records of 10,741 cholecystectomies performed between 1955 and 1998 were reviewed and recorded. The pathology slides were evaluated for evidence of calcification and gallbladder carcinoma. Fifteen (0.14%) of 10,741 specimens were porcelain gallbladders. Ten patients (67%) had symptoms suggestive of biliary colic or cholecystitis. Five (33%) were asymptomatic and diagnosed incidentally. All specimens demonstrated chronic cholecystitis and partial calcification of the gallbladder wall. Nine (60%) had cholelithiasis. None had gallbladder carcinoma by recent review of pathologic material. During this same period 88 (0.82%) patients had gallbladder carcinoma, none of which showed calcification of the wall. This report represents the largest modern review of porcelain gallbladders. No carcinoma was identified among patients with porcelain gallbladder. In addition no patient with gallbladder carcinoma had calcified gallbladder. With a better understanding of the natural history of the porcelain gallbladder the current management of these patients may change. PMID- 11206902 TI - Axillary lymph node status of T1 primary breast cancer in a diverse population. AB - The utility of level I and II axillary lymph node dissection in women with primary tumors less than 1 cm in diameter has recently received extensive evaluation. Numerous patients undergo axillary lymph node dissection ultimately to discover no pathological involvement. This study investigates the lymph node status in T1 primary breast adenocarcinoma in our diverse patient population. A retrospective evaluation of patients treated at the Medical Center of Louisiana at New Orleans and the Tulane University Medical Center with breast adenocarcinoma less than or equal to 2 cm was performed. Demographic data and pathological reports were reviewed to obtain breast lesion size and lymph node status. One hundred sixteen patients were found to have T1 lesions. Ethnic distribution was African American 66 per cent; Caucasians 30 per cent; Hispanic 2 per cent; and Asian 3 per cent. Whereas no patients with T1a lesions had positive lymph nodes, 11 per cent of patients with T1b lesions and 36 per cent of patients with T1c lesions had positive lymph nodes. However, in our patient population no patients with tumors less than 1.0 cm. in diameter had positive lymph nodes. Although this may be due to our relatively small sample size axillary lymph node dissection may be unnecessary in this select patient population. For patients with lesions 1.0 cm and greater an axillary lymph node dissection seems to add necessary information for correct treatment in a small percentage of patients. The use of lymphatic mapping with sentinel axillary lymph node biopsy may reduce the number of unnecessary axillary dissections in early breast cancer. PMID- 11206903 TI - Aerodigestive injuries of the neck. AB - Cervical aerodigestive trauma is rare and most centers have a limited experience with its management. The purpose of this review was to study the epidemiology, diagnosis, and problems related to the early evaluation and management of these injuries. This was a retrospective study based on trauma registry and on chart, operative, radiological, and endoscopic reports. There were 1560 admissions with blunt or penetrating trauma to the neck. The overall incidence of aerodigestive trauma was 4.9 per cent (10.2% for gunshot wounds, 4.6% for stab wounds, and 1.2% for blunt trauma). All patients with aerodigestive trauma had suspicious signs or symptoms on admission. The most common life-threatening problem in the emergency room and directly related to the aerodigestive trauma was airway compromise. Twenty-nine per cent of patients with laryngotracheal trauma required an emergency room airway establishment because of threatened airway loss. Although rapid sequence induction was successful in the majority of cases, in 11.9 per cent there was loss of airway and a cricothyroidotomy was necessary. Overall, 9 per cent of cases with aerodigestive injuries were successfully treated nonoperatively. Thirty-six per cent of patients with laryngotracheal trauma and surgical repair were successfully treated without a protective tracheostomy. There was no mortality due to the aerodigestive injuries. Cervical aerodigestive trauma is rare. In conclusion, all patients with significant aerodigestive injuries requiring treatment had suspicious signs and symptoms. Airway compromise was a common problem in the emergency room. Loss of airway after rapid sequence induction is a potentially lethal complication and the trauma team should be ready for a surgical airway. Repair of laryngotracheal injuries without a protective tracheostomy is safe in selected cases. PMID- 11206904 TI - Splenic abscess: report of six cases and review of the literature. AB - Splenic abscesses are rare but appear to be increasing in frequency. Recent advances in radiologic techniques have affected the diagnosis and management. The purpose of this study was to evaluate these effects. The medical records of one institution were retrospectively reviewed and six cases of splenic abscesses seen between 1989 and 1999 were identified. All patients had predisposing conditions with metastatic hematogenous infection in three and one each with trauma, immunodeficiency, and a contiguous site of infection. Fever was present in all patients with chills and vomiting in five and three patients, respectively. Left upper quadrant tenderness appeared in four patients and leukocytosis was found in every patient except one with the acquired immunodeficiency syndrome. Chest roentgenograms were abnormal in five patients with a left pleural effusion most common. Ultrasound revealed the defect in both patients it was utilized in and computed tomography was diagnostic in all cases. The causative organisms were anaerobes in two cases and Candida albicans, Streptococcus viridans, Escherichia coli, and Citrobacter freundii each present in one case. Radiology guided percutaneous drainage was attempted in four patients but was only successful in one. Splenectomy with antibiotics was curative in the remainder with a 100 per cent survival. These data suggest that percutaneous drainage may be appropriate for certain patients initially, but the high failure rate demonstrates that splenectomy remains the standard treatment. PMID- 11206905 TI - The potential value of intraoperative imprint cytology of axillary sentinel lymph nodes in breast cancer patients. AB - Axillary sentinel nodes predict the node status and may allow dissection of the axilla on a selective basis. Seventy-two sentinel nodes from 60 patients identified with Patent blue and/or the high radioactivity due to the uptake of 99m-Tc-labeled colloidal albumin were bisected for hematoxylin and eosin-stained touch preparations. The sentinel nodes were submitted in toto for permanent step sections and immunostained for cytokeratins. The imprints had a sensitivity of 83 per cent, a negative predictive value of 86 per cent, and a false negative rate of 17 per cent when the cut surface histology was considered. These corresponding values were 59, 68, and 41 per cent on a patient basis when the whole sentinel node histology was considered as many micrometastases did not appear in the cut surface sampled by the imprints. Although up to two-fifths of patients with tumor cells in the sentinel lymph nodes may be undetected by the method imprint cytology is valuable in the intraoperative assessment of sentinel nodes. This series suggests that 78 per cent of the patients can be adequately selected for a one-step axillary operation on the basis of intraoperative imprints. Results may be improved if the surface sampled is appropriately large and well selected. PMID- 11206906 TI - Game theory in the operating room environment. AB - To optimize the functioning of an operating room the interactions of the staff (physicians and nurses) and other stakeholders (administrators) must be understood. Game theory provides a representation of the interactions that typically take place in the operating room environment. By understanding the types of games/interactions that occur the participants can better predict outcome and adapt their own behavior to optimize that outcome. Types of games seen in the operating room include fixed-sum, zero-sum, and non-zero-sum games. The Prisoner's Dilemma game and some of its variations are used to illustrate common interactions in the operating room. Examples of strategies for typical scenarios are discussed as well as ways to improve the outcome of the games. A better understanding of human behavior can improve the functioning of complex systems such as that found in the operating room. PMID- 11206907 TI - Acute cholecystitis in the immediate postoperative period following esophagogastrectomy. AB - Postoperative acute cholecystitis (PAC) occurs after 0.06 per cent of all operations. However, PAC may occur in up to 3.1 per cent of patients after gastrectomy. This increased incidence of PAC is due to bile stasis and gall bladder ischemia promoted by vagotomy and gastrohepatic ligament dissection during gastrectomy. Despite similar factors during esophagogastrectomy PAC is rarely reported in large American series of patients undergoing esophagogastrectomy. We report two cases of PAC occurring after esophagogastrectomy. PMID- 11206908 TI - Comparison of the column performance of narrow-bore and standard-bore columns for the chromatographic determination of alpha-, beta-, gamma-, and delta-tocopherol. AB - A comparison of the performance of narrow-bore (2.1-mm i.d.) and standard-bore (4.6-mm i.d.) analytical silica columns having the same length is completed for the resolution of alpha-, beta-, gamma-, and delta-tocopherol. The studies are performed on high-performance liquid chromatographic equipment with minimum extracolumn contribution. Column permeabilities are 1.16 x 10(-9) and 2.48 x 10( 9) cm2 for narrow and standard bore, respectively. The narrow-bore column gives up to a 7 times increase in sensitivity compared with a standard-bore column at equivalent running times for the analytes. Approximately one-third solvent savings can be achieved with the narrow-bore column. Theoretical plates of the standard-bore column are higher than that of the narrow-bore column. PMID- 11206909 TI - Method development and validation for the determination of various sulfur containing anions and other anions in the corrosion process by capillary ion electrophoresis with indirect detection. AB - A method of capillary ion electrophoresis with indirect detection is developed for the simultaneous determination of the sulfur-containing anions S2O4(2-), S2O3(2-), SO4(2-), SO3(2-), and S2- and other anions (Cl-, Br-, NO2-, NO3-, (COO)2(2-), F-, and PO4(3-)) in the corrosion process. The effects of pH, tetradecyltrimethylammonium hydroxide, chromate, 2-[n-cyclohexylamino]-ethane sulfonate, calcium gluconate, and acetonitrile on the migration and resolution of the anions and the stability of sulfur-containing anions are systematically investigated. The detection limits, repeatability, and linearity for the anions are comparatively studied at 374, 274, and 254 nm, and the results show that 374 nm is the optimal length. The simultaneous multiwavelength detection at 374, 254, 214, and 195 nm can assist in confirming the identification of UV-absorbing anions. PMID- 11206910 TI - Industrial scale-up of countercurrent chromatography: predictive scale-up. AB - This study describes how scale-up in countercurrent chromatography (CCC) can be simply predicted on a process scale CCC device by running a preliminary analytical-sized sample and having knowledge of the stationary-phase retention at scale-up conditions. Results have shown that simple experimentation can lead within a day to a process with the capability of several kilograms per day (tons per year) compound yield, and that this is feasible with benchtop CCC units. PMID- 11206911 TI - Quantitative structure-retention relationships with model analytes as a means of an objective evaluation of chromatographic columns. AB - The performance of several previously designed model series of test analytes has been tested to characterize in an objective, quantitative manner modern stationary phases for reversed-phase high-performance liquid chromatography (RP HPLC) using quantitative structure-retention relationships (QSRRs). Three QSRR approaches and three respective series of test analytes recommended for studies of the molecular mechanism of chromatographic retention are employed: the reduced linear solvation energy relationship (LSER)-based model of Abraham, a model employing structural descriptors from molecular modeling, and a model relating retention to the n-octanol-water partition coefficient log P. All of the models and test analytes proposed provide reliable QSRR equations. Those equations discriminate in quantitative terms individual columns and chromatographic systems and can be interpreted in straightforward rational chemical categories. In view of QSRRs, the differences in the intermolecular interactions between a given stationary phase and a structurally defined analyte rationalize the observed differences in retention. The QSRR models (previously derived retrospectively) are demonstrated to work well on new sets of RP-HPLC data. At the same time, it has been confirmed that the three test series of analytes have properly been designed and can be recommended for comparative studies of analytical columns. QSRRs once derived on a given column for model analytes can be used to predict the retention of other analytes of a defined structure. That in turn can facilitate the procedure of the rational optimization of chromatographic separations. PMID- 11206912 TI - Liquid chromatographic determination of the total available free and intrachain lysine in various foods. AB - A method for the quantitative determination of the total available lysine in various foods is developed. The method is based on the reaction of the amino groups on the lysine molecule with fluorodinitrobenzene and is capable of furnishing simultaneous determination of the available intrachain lysine (known as N-epsilon-[2,4-dinitrophenyl]-L-lysine) or the available free and/or N terminal lysine (known as N,N'-di-[2,4-dinitrophenyl]-L-lysine). Optimum conditions for separation and quantitation are studied. The results show the proposed method to be both accurate and precise and suitable for food samples containing hydrolyzed proteins. PMID- 11206913 TI - Rejuvenate columns that have experienced peak-shape deterioration. PMID- 11206914 TI - Stability-indicating high-performance liquid chromatographic assay method and photostability of carprofen. AB - A rapid, sensitive, and accurate stability-indicating high-performance liquid chromatographic assay method for determining the degradation of carprofen (CPF) is developed and validated under acidic, basic, or photo-irradiated conditions. The analysis is monitored with a Cosmosil 5C18-AR column using a mobile phase of CH3CN-H2O-AcOH (50:49:1, v/v/v) at 260 nm. The developed method satisfies the system suitability criteria, peak integrity, and resolution among the parent drug and its degradation products. The results indicate that the established assay method shows good selectivity and specificity suitable for stability measurements of CPF. CPF is found to be more sensitive to exposure to light and in acidic conditions, but it is stable in a basic medium. The kinetic study of the photodegradation of CPF follows an apparent first-order reaction in a variety of solvents. The solvent effects on the rates of degradation are in the decreasing order of chloroform > dichloromethane > methanol > ethanol > 2-propanol, which is irrelevant to the dielectric constant epsilon. However, the hydrogen-donating ability of the solvents is essential to the photochemical decomposition of CPF. A plot of log k versus the Kirkwood function exhibits a linear relationship in aqueous ethanolic solutions, which implies that degradation proceeds via an ionic mechanism. PMID- 11206915 TI - Therapeutic perspectives of in vivo cell electropermeabilization. AB - Cell electropermeabilization (also termed cell electroporation) is nowadays a routine technique used in biochemical and pharmacological studies for the in vitro introduction of nonpermeant molecules into living cells. But electric pulses can be used as well in vivo for the delivery of drugs or DNA into cells of tissues. This review then gives an updated overview of the therapeutic perspectives of cell electropermeabilization in vivo, in particular of the antitumour electrochemotherapy (i.e., the combination of a cytotoxic nonpermeant drug with permeabilizing electric pulses delivered to the tumours) and of in vivo DNA electrotransfer for gene therapy. After a short summary of the present knowledge on cell electropermeabilization (particularly in vivo), the basis, the present achievements, and the challenges of electrochemotherapy are described and discussed, which includes an overview of still open questions and an update on recent clinical trials. DNA electrotransfer for gene therapy is an emerging field in which results are rapidly accumulating. Present knowledge on DNA electrotransfer mechanisms, as wel as the potentialities of DNA electrotransfer to become an efficient non-viral approach for gene therapy, are reviewed. PMID- 11206916 TI - An electrochemical evidence of free radicals formation from flutamide and its reactivity with endo/xenobiotics of pharmacological relevance. AB - This paper reports the feasibility of free radicals formation from flutamide by using cyclic voltammetry. The electrochemical characteristics and the reactivity of the one-electron reduction product from flutamide in mixed media with thiol compounds and the nuclei acid bases are characterized. Results from this paper show the thermodynamic feasibility of free radical formation expressed for both the cathodic peak potential and the second-order rate constant values. The reactivity of the radical towards thiol compounds (glutathione, cysteamine, N acetylcysteine) and the nuclei acid base, adenine, thymine and uracil were quantitatively assessed through the calculation of the respective interaction rate constants. Based on these results, the following tentative order of reactivity towards the xeno/endobiotics is as follows: cysteamine > uracil > glutathione > adenine > N-acetylcysteine > thymine. The stability of the nitro radical anion electrochemically generated from flutamide showed a linear dependence with pH. PMID- 11206917 TI - Electrooxidation of phenol by catalase immobilized on graphite electrodes. AB - Electrocatalytic properties of catalase (CAT) immobilized on graphite and soot to mediate electrooxidation of phenol have been investigated. The kinetic parameters -Km, k(s), deltaG*Ar and Z0 of the process studied were calculated. Conclusions on a probable mechanism of the biocatalytic and electrochemical process observed were drawn from the calculated values of activation and kinetic parameters. A quantitative UV-spectrophotometrical approach was used as an analytical tool. The electrochemical oxidation of phenol was examined with potentiodynamic and polarization curves' method. PMID- 11206918 TI - The proton uptake channel of bacteriorhodopsin as studied by a photoelectrochemical method. AB - A series of the mutant proteins (D96N, D96N/D85N, D115N, L93T, T46V, V49A) where the residues are located at the cytoplasmic domain of bacteriorhodopsin (bR) were studied photoelectrochemically and their photocurrent response characteristics at the electrode/electrolyte interface were compared with those of the wild-type bR. While the wild-type bR of normal proton pumping activity yields symmetrical cathodic (positive) and anodic (negative) responses, corresponding to proton release and proton uptake, respectively, these mutants, with the exception of D115N, showed diminished amplitudes in the negative response. This indicates retardation of proton translocation from the cytoplasmic surface to the retinal Schiff base. The mutation that gave the strongest influence on the negative response was D96N while moderate influence was obtained with L93T, T46V, and V49A. These results suggest that residues other than D96 also participate in the cytoplasmic proton uptake channel, either by interacting with D96 directly or by forming a hydrogen-bonded network with water molecules. The D96N/D85N double mutant yielded little response at neutral pH, but the response was partially recovered by addition of azide, while it was fully recovered in the single mutant D96N. The D115N mutant showed the response profile that closely resembles the wild-type, indicating that D115 is not crucially involved in the event of proton transfer relay at the cytoplasmic region. It was also found that every mutant in this study releases protons prior to uptake at the other membrane surface, as does the wild-type. PMID- 11206919 TI - Influence of the hydrodynamics on the biofilm formation by mass transport analysis. AB - Biofilm are formed wherever there is some water in our environment: pipes, pipelines, tap water systems, air conditioning systems... Furthermore, the ecological and economical consequences are very important: energy losses, bacterial contamination, material deterioration. The aim of this work is to develop a new method to detect and monitor the biofilm formation. This method can also determine some mechanical properties of the biofilm. An application of this method is a realization of a biofilm sensor. Biofilm is considered as an inert porous layer with respect to mass transport. In our experiment, the biofilm is grown on a gold electrode in natural seawater. Its thickness is determined by considering the oxygen diffusion limiting current measured for different rotation speeds on this electrode. Two different incubators are used during the biofilm development: one, with a laminar flow, permits the rotation of the electrode during the biofilm formation, and for the second, a tube is used under turbulent conditions during the biofilm formation. This experiment allows us to characterize the mechanical behavior (thickness, elasticity, rigidity) of the biofilm in function of different conditions of development. PMID- 11206920 TI - Acute effects of whole-body exposure to static magnetic fields and 50-Hz electromagnetic fields on muscle microcirculation in anesthetized mice. AB - Acute microhemodynamic effects of static and alternating magnetic fields at a threshold level were investigated on modulating the muscle capillary mirocirculation in pentobarbital-anesthetized mice. The skin in a tibialis anterior was circularly removed with 1.5 mm diameter for intravital-microscopic recording of the capillary blood velocity in the tibialis anterior muscle. Fluorescein isothiocyanate (FITC)-labeled dextran (MW 150 kDa) was used for an in vivo fluorescent plasma marker of the muscle capillaries. Following a bolus injection of FITC-dextran solution into the caudal vein, the peak blood velocity in the muscle capillaries was measured prior to, during, and following exposure to static magnetic fields (SMF) or 50-Hz electromagnetic fields (EMF) using a fluorescence epi-illumination system. The whole body of experimental animals, placed on the observing stage of a fluorescence microscope, was exposed to SMF (0.3, 1 and 10 mT) or 50-Hz EMF (0.3 and 1 mT) for 10 min using a specially devised electromagnet. For sham exposure, the electromagnet was not energized. During exposure and post-exposure to SMF of 10 mT, the peak blood velocity significantly increased as compared to sham exposure. After the withdrawal of SMF and 50-Hz EMF of 1 mT, significant similar effects on the blood velocity were present or enhanced. These findings suggest that field intensity of 1 mT might be considered as a threshold level for enhancing muscle microcirculation under pentobarbital-induced hypnosis. PMID- 11206921 TI - 25 Hz electromagnetic field exposure has no effect on cell cycle distribution and apoptosis in U-937 and HCA-2/1cch cells. AB - It is reported that exposure to 50 Hz extremely low-frequency electromagnetic field (ELF-EMF) can produce apoptosis and small variations in cell cycle distribution on different cell lines. In order to study the effect of ELF-EMF on tumoral cells in vitro, two cell lines (U-937, from a histiocytic lymphoma, and HCA-2/1cch, from a human colon adenocarcinoma) were exposed to 25 Hz, 1.5 mT, for 2 h and 45 min. Cell cycle distribution, apoptosis (spontaneous and dexamethasone induced) and cell growth were evaluated. Neither significant alteration in cell cycle phases nor induction of apoptosis was observed. Nevertheless, the relative cell number was found to decrease to 55.84+/-7.35% (p <0.05, Student's t-test) for HCA-2/1cch cells after exposure to EMF in the presence of dexamethasone. The presence of dexamethasone during the EMF exposure could probably produce a decrease in the cell growth of this cell line. PMID- 11206922 TI - Direct electrochemistry of heme proteins: effect of electrode surface modification by neutral surfactants. AB - Direct electrochemical studies on horse heart myoglobin and horseradish peroxidase (HRP) have been carried out using tin-doped indium oxide (ITO) and surfactant modified glassy carbon working electrodes. These proteins show very slow electron transfer kinetics at metal or untreated electrodes. Moreover, small amounts of surface-active impurity were drastically affects the electrode reaction of these proteins. The results showed that modification of the electrode surface with neutral surfactants significantly improves the electrochemical response of myoglobin as well as of HRP. The electrode response was found to depend on the structure of the surfactants. The amount of surfactant required per unit area of the electrode surface to promote the maximum electron transfer rate constants was found to be constant. This indicated that the surfactant molecules interacted with the electrode surface in a specific manner and anchored the protein molecules to align in the suitable orientation. The hydrophobicity of the surfactants rather than their charge was found to be crucial in promoting the electrode response of these proteins at the glassy carbon electrode. PMID- 11206923 TI - Control by membrane order of voltage-induced permeabilization, loading and gene transfer in mammalian cells. AB - Cells can be transiently permeabilized by application of electric pulses. A direct consequence of this treatment is to create a new state in the membrane leading to DNA and protein transfers. A key step, in the interaction between macromolecules and the electropermeabilized membrane, is involved. We previously reported that membrane and DNA associated hydration and undulation forces appeared to be involved in this process by studying the effects of osmotic pressure. Effects of ethanol (EtOH) and L-alpha-lysophosphatidylcholine (lyso PC), molecules known to affect membrane order and therefore undulation forces, were investigated on Chinese hamster ovary (CHO) cells. We used millisecond square wave pulses, conditions giving high efficiency for gene transfer. No effect was observed on cell permeabilization for small sized molecules. Only little change on electroloading of proteins such as R-phycoerythrin was obtained in presence of EtOH. But, a decrease (increase) in electrotransfection was observed for cells treated with EtOH (lyso-PC). Under our conditions, no additional effects of the chemical treatment were observed on cell viability and on membrane resealing. These results tentatively explained in terms of the effect of membrane order on membrane organization and interaction between molecules and membrane supports the existence of the plasmid-membrane interaction in the mechanism of electrically mediated gene transfer. PMID- 11206924 TI - Kinetic modeling of the photosynthetic electron transport chain. AB - A simulation model of the photosynthetic electron transport chain operating under steady state conditions is presented. The model enables the calculation of (1) the rates of electron transport and transmembrane proton translocation, (2) the proton/electron stoichiometry, (3) the number of electrons stored in the different redox centers and (4) the stationary transmembrane pH difference. Light intensity and proton permeability of the thylakoid membrane are varied in order to compare the predictions of the model with experimental data. The routes of electron transport and proton translocation are simulated by two coupled arithmetic loops. The first one represents the sequence of reaction steps making up the linear electron transport chain and the Q-cycle. This loop yields the electron flow rate and the proton/electron ratio. The second loop balances the H+ fluxes and yields the internal H+ concentration. The bifurcation of the electron transport pathways at the stage of plastoquinol oxidation is obligatory. The first electron enters always the linear branch and is transferred to photosystem I. The electron of the remaining semiquinone can enter the Q-cycle or, alternatively, the semiquinone can be lost from the cytochrome b6f complex. The competition between these two reactions explains the experimentally observed variability of the proton/electron ratio. We also investigated additional model variants, where the variation of the proton/electron stoichiometry is attributed to other loss reactions within the cytochrome b6f complex. However, the semiquinone detachment seems to be the best candidate for a satisfactory description of the experimental data. Additional calculations were done in order to assess the effects of the movement of the Rieske protein on linear electron transport; it was found that this conformational change does not limit the electron transport rate, if it occurs with a time constant of at least 1000 s( 1). PMID- 11206925 TI - Dissociation and electrooxidation of primaquine diphosphate as an approach to the study of anti-chagas prodrugs mechanism of action. AB - This paper describes the voltammetric behavior of primaquine as a previous support to the further understanding of the delivery and action mechanisms of its respective synthesized prodrugs. There are few papers describing the drug behavior and most of the time no correlation between oxidation process and pH is done. Our results showed that primaquine oxidation is a one-step reaction involving two electrons with the charge transfer process being strongly pH dependent in acid medium and pH-independent in a weak basic medium, with the neutral form being easily oxidized. This leads to the conclusion that quinoline nitrogen ring neutralization is a determinant step to the formation of the oxidized primaquine form. The existence of a relationship between the primaquine dissociation equilibrium and its electrooxidation process is shown. This work points the importance of voltammetric methodology as a tool for further studies on quantitative relationship studies between chemical structure and biological activity (QSAR) for electroactive drugs. PMID- 11206926 TI - Enzymatic oxidation of cadmium and lead metals photodeposited on cadmium sulfide. AB - Cadmium and lead metals deposited on CdS particles are shown to act as substrates -electron donors for enzymes, hydrogenase from Thiocapsa roseopersicina (HG), NAD dependent hydrogenase from Alcaligenes eutrophus (NLH), and ferredoxin:NADP oxidoreductase (FNR) from Chlorella in the formation of hydrogen, NADH and NADPH, respectively. Adsorption of the enzyme on the surface of the metallized CdS particle is required for enzymatic oxidation of metal. The maximum rates for the formation of hydrogen and NADH catalyzed by hydrogenase and NAD-dependent hydrogenase with metals as electron donors are comparable with the rates obtained for these enzymes using soluble substrates. Kinetic analysis of the enzymatic oxidation of cadmium metal has revealed that the rate decreases mainly due to the formation of a solid product, which is supposed to be Cd(OH)2. The deceleration of lead oxidation catalyzed by hydrogenase proceeds at the expense of the inhibitory effect of the formed Pb2+. The enzymatic oxidation of electrochemically prepared cadmium metal is also shown. Based on these results, a new mechanism of action of the enzymes involved in anaerobic biocorrosion is proposed. By this mechanism, the enzyme accelerates the process of metal dissolution through a mediatorless catalysis of the reduction of the enzyme substrate. PMID- 11206927 TI - ELF magnetic fields initiate protein tyrosine phosphorylation of the T cell receptor complex. AB - The human T cell line Jurkat registers a sinusoidal extremely low frequency (ELF), 0.10 mT magnetic fields (MFs) at the level of the plasma membrane. In this study, the protein tyrosine phosphorylation (PY) of two membrane-associated proteins in Jurkat cells were examined following a short-term MFs exposure, the zeta chains and the Src kinases p56lck. These proteins are interesting to study since the earliest biochemical event upon T cell receptor (TcR) activation is PY of the zeta chains. These signalling chains in the TcR complex was assessed using Western blotting and the activation of the p56lck kinase was analysed by in vitro kinase assay. The MFs exposure of Jurkat for 5 min activated p56lck and resulted in PY of zeta. These findings are in line with earlier reports on how MFs exposure affects signal transduction in Jurkat. PMID- 11206929 TI - Mechanical and electromagnetic induction of protection against oxidative stress. AB - Cells and tissues can be protected against a potentially lethal stress by first exposing them to a brief dose of the same or different stress. This "pre conditioning" phenomenon has been documented in many models of protection against oxidative stress, including ischemia/reperfusion and ultraviolet (UV) light exposure. Stimuli which induce this protective response include heat, chemicals, brief ischemia, and electromagnetic (EM) field exposures. We report here that constant mechanical vibration pre-conditions chick embryos, protecting them during subsequent stress from hypoxia or UV light exposure. Continuously mechanically vibrated embryos (60 Hz, 1 g (32 ft/s2), 20 min) exhibited nearly double the survival (67.5%, P < 0.001) after subsequent hypoxia as compared to non-vibrated controls (37.6%). As a second set of experiments, embryos were vibrated and then exposed to UV light stress. Those embryos that were vibrated prior to UV had nearly double the survival 3 h after UV exposure (66%, P < 0.001) as compared to controls (35%). The degree of protection, however, was dependent on the constancy of the vibration amplitude. When vibration was turned on and off at 1-s intervals throughout exposure, no increase in hypoxia protection was noted. For 50 s on/off vibration intervals, however, hypoxia protection comparable to continuous vibration was obtained. In contrast, random, inconstant mechanical vibration did not induce protection against subsequent UV exposure. These data suggest that to be an effective pre-conditioning agent, mechanical vibration must have a degree of temporally constancy (on/off intervals of greater than 1 s). Further experiments in both models (hypoxia and UV) indicated an interaction between vibration and EM field-induced protection. Vibration-induced hypoxia protection was inhibited by superposition of a random EM noise field (previously shown to inhibit EM field-induced protection). In addition, EM field induced UV protection was inhibited by the superposition of random mechanical vibration. Thus, the superposition of either vibrational or EM noise during pre conditioning virtually eliminated protection against hypoxia and UV. This link between EM field exposures and mechanical vibration is consistent with the hypothesis that cells sense these stimuli via a similar mechanism involving counter ion displacement. PMID- 11206928 TI - Charge displacement by adhesion and spreading of a cell. AB - The potentiostatic control of surface charge density and interfacial tension of an electrode immersed in an aqueous electrolyte solution offers a possibility for direct studies of non-specific interactions in cell adhesion. Unicellular marine alga, Dunaliella tertiolecta (Chlorophyceae) of micrometer size and flexible cell envelope was used as a model cell and 0.1 M NaCl as supporting electrolyte. The dropping mercury electrode acted as in situ adhesion sensor and the electrochemical technique of chronoamperometry allowed measurement of the spread cell-electrode interface area and the distance of the closest approach of a cell. The adhesion and spreading of a single cell at the mercury electrode causes a displacement of counter-ions from the electrical double layer over a broad range of the positive and negative surface charge densities (from +16.0 to -8.2 microC/cm2). The flow of compensating current reflects the dynamics of adhesive contact formation and subsequent spreading of a cell. The adhesion and spreading rates are enhanced by the hydrodynamic regime of electrode's growing fluid interface. The distance of the closest approach of an adherent cell is smaller or equal to the distance of the outer Helmholz plane within the electrical double layer, i.e. 0.3-0.5 nm. There is a clear evidence of cell rupture for the potentials of maximum attraction as the area of the contact interface exceeded up to 100 times the cross-section area of a free cell. PMID- 11206930 TI - The direct electrochemistry of myoglobin at a DL-homocysteine self-assembled gold electrode. AB - A pair of well-defined redox waves of myoglobin at a DL-homocysteine self assembled gold electrode was achieved. Myoglobin can strongly bind to the homocysteine self-assembled gold electrode, so the Mb-Hcy self-assembled gold electrode was prepared and the standard rate constant (ks) of Mb was calculated as 9.3 x 10(-1) s(-1). X-ray photoelectron spectroscopy (XPS) measurements demonstrated that Hcy monolayer was formed and Mb was bound to Hcy monolayer. PMID- 11206931 TI - Choriocarcinoma-induced suppression of lymphocyte activity. AB - The aim of the investigation was to study the influence of human choriocarcinoma cell culture supernatants (HCS) on the expression of lymphocyte surface molecules. Lymphocytes were stimulated with phytohemagglutinin in culture medium supplemented with 50% HCS. After 12 h and 60 h, fluorescence-activated cell sorter analysis was performed with specific monoclonal antibodies. After 12 h of incubation, the cell surface expression of the classical activation markers CD25, CD69, CD71, CD134 and CD3/HLA-DR, as well as of the apoptosis marker CD95 were significantly suppressed by HCS. Qualitatively similar results were obtained after 60 h. It was concluded that choriocarcinoma-induced suppression might be related to a nearly complete block in the cell cycle at early activation steps. The clinical and biological relevance of this phenomenon for the maternal-fetal tolerance are briefly discussed. PMID- 11206932 TI - Tolerance of immunotherapy with a standardized extract of Alternaria tenuis in patients with rhinitis and bronchial asthma. AB - We studied the safety of immunotherapy with an Alternaria extract in patients with rhinitis and bronchial asthma. The few studies that have investigated immunotherapy with mold allergens suggest that they cause adverse reactions more frequently than do other extracts. All treatments prescribed by our allergology service with Alternaria immunotherapy between 1988 and 1996 were recorded and analyzed. In all cases a biologically standardized depot extract of Alternaria tenuis containing 5 BU/ml was used according to a conventional immunotherapy schedule. During the study period 129 patients received immunotherapy with Alternaria extract. Of the 3,892 doses given, 1.95% led to adverse reactions, which occurred in 39.5% of the patients. Most of the adverse reactions were systemic and mild, and reproduced the underlying disease. The risk of adverse reactions was significantly higher in children, patients with asthma, and during the initial phase of treatment. Patients who suffered from adverse reactions had a significantly higher level of total and specific IgE. It was concluded that tolerance of Alternaria mold extract was worse than for other allergenic extracts, although most reactions recorded were mild. The risk of adverse reactions was greater in children and patients with asthma, and during the initial phase of immunotherapy. PMID- 11206933 TI - Bronchial asthma healthcare costs in Mexico: analysis of trends from 1991-1996 with information from the Mexican Institute of Social Security. AB - Cost trends for bronchial asthma have not been previously estimated in Mexico. The increasing prevalence of bronchial asthma as well as its elevated costs make it necessary to expand the availability of information for health planners. This is a growing problem which has been given little attention in national health reports. We did a descriptive, retrospective analysis using national data from the Mexican Institute for Social Security. We estimated the number of medical consultations provided by the state family medicine and specialty areas. A total of 756,843 consultations due to bronchial asthma were provided between 1991 and 1996 in the service areas under study. The healthcare expenditure for bronchial asthma showed an ascending and sustained trend during the study period. When analyzing the trends by type of service, a significant increase in in-hospital care was observed, ranging from US $14.5 (1991) to $19.8 (1996) million and a maximum of $28.4 (1994) million. A similar increase was found in specialty consultation, from $3.96 (1991) to $8.5 (1996) million; in emergencies, from $1. 1 (1991) to $2.9 (1996) million; and family medicine, from $0.66 (1991) to $0.79 (1996) million. Bronchial asthma follows the same pattern as other noncommunicable chronic diseases, increasing in highly urbanized areas and nationwide. In order to improve healthcare and maximize results with scarce resources, a set of strategies is presented to reduce bronchial asthma recurrence, decrease healthcare costs, and improve quality of life. PMID- 11206934 TI - Successful treatment of chronic idiopathic urticaria associated with thyroid autoimmunity. AB - The prevalence of thyroid autoimmunity is high in patients with chronic idiopathic urticaria (CIU), but in few selected patients the possible clinical benefit of levothyroxine sodium or antithyroid drugs has been studied. The objective of the present study was to confirm the prevalence of antithyroid antibodies in patients with CIU and to investigate the clinical response to levothyroxine sodium or methimazole. Antithyroglobulin and antiperoxidase antibodies were measured in 170 consecutive patients with CIU. Twenty-five (14.7%) had an antithyroglobulin or antiperoxidase antibody levels > 180 lU/ml and all but three were women. Twenty patients with CIU and thyroid autoimmunity were treated with levothyroxine sodium if hypothyroidism or normal thyroid function were present (18 patients) and with methimazole if hyperthyroidism was detected (two patients). Clinical response was evaluated by a clinical score. Autologous serum skin test before treatment was performed in 18 patients with thyroid autoantibodies. Urticaria resolved rapidly in two patients with Graves' disease. The clinical response of urticaria to levothyroxine sodium treatment was good in 15 patients and partial in two, whereas only one patient showed no improvement in clinical score (p < 0.0005). No changes in the antithyroglobulin or antiperoxidase levels were detected. Five patients reported adverse effects. The autologous serum skin test was positive in 10 patients and negative in eight. After successful treatment the test was repeated in six patients, proving negative in four and significantly diminished in two. We concluded that patients with CIU and thyroid autoimmunity benefit from treatment with levothyroxine sodium or antithyroid drugs. Antithyroid antibodies and positive autologous serum skin test in these patients could be markers of autoimmune disease with several target organs. PMID- 11206935 TI - Sensitization to different mite species in German farmers: clinical aspects. AB - Various mite species referred to collectively as house dust and storage mites are recognized worldwide as a cause of allergic airway disease. Our study aimed to investigate the frequency of sensitization and potential importance of mite species in farmers using a broad mite spectrum. A total of 86 German farmers with rhinitis and/or asthma were studied by skin prick testing and/or enzyme allergosorbent test (EAST) with the following mites: Blomia tjibodas, Blomia tropicalis, Blomia kulagini, Glycyphagus domesticus, Thyreophagus entomophagus, Euroglyphus maynei, Chortoglyphus arcuatus, Dermatophagoides pteronyssinus, Dermatophagoides farinae, Acarus siro, Lepidoglyphus destructor, Tyrophagus putrescentiae, Acarus farris and Cheyletus eruditus. Sensitization to at least one mite species was detected in 51 patients (59%) by skin prick testing, and in 31 patients (36%) by EAST. The most frequent sensitizations determined by skin tests were found for the three Blomia species, E. maynei and G. domesticus. Twelve patients (14%) gave a positive EAST with the predator mite C. eruditus. A total of 22 patients gave positive EAST results with the Dermatophagoides species. We were able to document sensitization to C. arcuatus, E. maynei and T. entomophagus for the first time in Germany. A considerable proportion of the German farmers tested were sensitized to storage mites. The allergological potential of various mite species has been recognized, some for the first time. It was concluded that B. tjibodas, G. domesticus, C. arcuatus and C. eruditus in particular should be included in an allergy diagnosis. Further investigations into the clinical relevance of the sensitizations and possible cross-reactivity between the mite species are necessary. PMID- 11206936 TI - Clinical and immunological spectrum of partial DiGeorge syndrome. AB - We present four cases of DiGeorge syndrome diagnosed at our center. Onset occurred during the neonatal period and was associated with severe congenital heart disease. In case 1, the patient had heart disease and absence of thymus. Total T-lymphocytes were 34%; total T4-lymphocytes were 27%. Stimulation test with phytohemagglutinin (PHA), concanavalin A (conA) and pokeweed mitogen were negative. Microdeletion was found in the chromosome 22q11 region. The second case involved heart disease, microstomia, round and rotated ears and branchial cyst. Total T-lymphocytes were 38% and total T4-lymphocytes 27%. Thymus was absent. Microdeletion in the chromosome 22q11 region. Case 3 showed heart disease, renal malformation, absence of thymus and parathyroid gland. The patient died 5 days postsurgery. Microdeletion was seen at chromosome 22q11. In the fourth case there was heart disease, microretrognathia, hypertelorism, short neck, absence of thymus and parathyroid glands. Total T-lymphocytes were 22%, total T4-lymphocytes 15%, and total T lymphocytes for pokeweed mitogen were negative. Microdeletion was found at chromosome 22q11. At the age of 13 days the patient died. The cases were recorded during a 2-year period, between 1997 and 1998. The prevalence of DiGeorge syndrome in the number of admissions for congenital heart disease among the neonates at our hospital was 3.14%. Presentation in the form of repeated infections is rare, since most cases of DiGeorge syndrome are partial, and functional cellular immunity is preserved. PMID- 11206937 TI - Isolation and partial characterization of Fes p 4 allergen. AB - More than 75% of grass pollen-allergic patients produce specific IgE antibodies against group-4 allergens. Purification and characterization of different grass group-4 allergens should help to further understand their allergenicity. In this study, an attempt was made to isolate and characterize Fes p 4 allergen by several biochemical and immunochemical methods. Fes p 4 was purified by a combination of chromatographic techniques (gel permeation and ion exchange chromatography). Isolated protein revealed four main spots at a molecular weight of 60 kDa and a pI ranging from 8.7 to 9.1. Eight sera were selected from patients with positive result of skin prick test to the mixture of grass pollen extracts. ELISA inhibition technique was used to study Fes p 4-specific IgE in the patients' sera. ELISA to Festuca pratensis was inhibited up to 80% by F. pratensis pollen extract and up to 48% by Fes p 4. 2D-PAGE-immunoblot was used to identify allergenic and antigenic components of Fes p 4 with patients' IgE and monoclonal antibodies (MABs). Three components of purified protein expressed IgE binding ability. Two MABs which recognized unrelated regions on Phl p 4, bound three components of Fes p 4. The role of the carbohydrate moiety in allergenicity was examined with individual patient sera by using periodate-treated Fes p 4. Six out of eight patients reduced IgE binding to periodate-treated allergen. Isolated Fes R 4 glycoprotein consisted of four components, three of which were allergenic, and share common epitopes specific for grass group-4 homologs. The results of periodate oxidation of Fes p 4 suggest that the carbohydrate moiety is involved in IgE binding. PMID- 11206938 TI - Dermographism and atopy in patients with Behcet's disease. AB - Dermographism is the appearance of whealing and erythema within minutes in a site where skin has been exposed to pressure or mechanical irritation. In our clinical observations, dermographism seems to be frequent in patients with Behcet's disease. Since the prevalence of allergic responses is reportedly increased in vasculitic syndromes, we aimed to assess dermographism and atopy in a group of Behcet's patients. The study group comprised 30 consecutive patients with Behcet's disease. The study was carried out in two parts: elicited dermographism and atopy tests. In the first part, dermographism was investigated in the study group (Behcet's patients) and 230 healthy controls. In the second part, the study group, 30 healthy controls and 17 patients with allergic bronchial asthma were evaluated for specific and nonspecific atopy. Dermographism was found to be increased in patients with Behcet's disease. Peripheral blood eosinophil count, serum total IgE and nasal eosinophil scores were similar in patients with Behcet's disease and healthy controls. Although blood eosinophil count and serum total IgE levels were higher in allergic bronchial asthma patients than in Behcet's patients, the difference was significant only in the former. Skin prick test was positive in three of the patients with Behcet's disease and in six healthy controls. The difference was statistically insignificant (p > 0.05). None of the Behcet's disease patients had pathergy or a pathergy-like reaction at the site of the skin prick test after 48 h. In conclusion, our results confirm the general impression that dermographism is common in patients suffering from Behcet's disease. PMID- 11206939 TI - Allergy to ethylenediamine and steroid. AB - Intravenous preparations combining aminophylline and a steroid are used frequently in the treatment of bronchial asthma attacks. However, anaphylactoid reactions to such preparations have been rarely observed. We report the case of a 31-year-old man with aminophylline and steroid allergy. Aminophylline is the ethylenediamine salt of theophylline. In our patient, aminophylline, ethylenediamine and various steroids were found to be positive in the intradermal test. The challenge test with intravenous aminophylline was positive, while that with oral theophylline was negative. Ethylenediamine is used in everyday products such as shellacs and rubber products. In the case of our patient, his asthma worsened following the remodelling of his restaurant. Occupational asthma due to exposure to ethylenediamine is also discussed. PMID- 11206940 TI - Non-X-linked hyperimmunoglobulin M syndrome with chronic interstitial pneumonitis. AB - Hyperimmunoglobulin M (IgM) syndrome is a rare primary immunodeficiency disorder, and the non-X-linked form of this syndrome is even more infrequent. We report the clinical case of a 6-year-old girl. Her disease began at the age of 1 year when she experienced bronchial obstruction. When she was 3 years old she developed severe recurrent respiratory infections of unusual clinical course. Serum IgM was elevated and the other serum immunoglobulins were absent. Cellular immune response was impaired, with severe depression of delayed hypersensitive cutaneous response and of proliferative response to mitogens. The CD40 ligand expression decreased. Chest CT scan showed areas of lung condensation, bronchial dilatation and signs suggesting interstitial pneumonitis. The latter was confirmed by a biopsy showing a high number of Langerhans' cells and an early-stage fibrosis. She was treated with antibiotics, inhaled bronchodilators and corticosteroids, intravenous immunoglobulin, chloroquine and prednisone. Despite the substitution therapy, her clinical course was slow, with respiratory infections and oxygen dependance. The follow-up thoracoscopic biopsy performed after 18 months of immunosuppressant therapy showed a progression of fibrosis and a decrease in the inflammatory infiltrate. PMID- 11206941 TI - Chronic urticaria associated with chronic myelomonocytic leukemia. AB - Although chronic urticaria is usually idiopathic, in rare cases it may be a sign of underlying malignancy. We describe the first case of chronic urticaria associated with chronic myelomonocytic leukemia. The urticarial lesions healed successfully with etoposide, an antineoplastic agent. This case demonstrates that cases of chronic urticaria should not to be labeled as idiopathic until diligent evaluation has failed to reveal a cause. PMID- 11206942 TI - Randomized trial of a patient decision aid for choice of surgical treatment for breast cancer. AB - A decision aid for the surgical treatment of early breast cancer was evaluated in a randomized controlled trial. The decision aid, a tape and workbook, includes explicit presentation of probabilities, photographs and graphics, and a values clarification exercise. Community surgeons were randomized to use the decision aid or a control pamphlet. Patients completed a questionnaire prior to using the decision aid, after reviewing it but prior to surgery, and 6 months after enrollment. There was no difference in anxiety, knowledge, or decisional regret across the 2 groups. There was a nonsignificant trend toward lower decisional conflict in the decision aid group. A subgroup of women who were initially leaning toward mastectomy or were unsure had lower decisional conflict. Although the decision aid had minimal impact on the main study outcomes, a subgroup may have benefited. Such subgroups should be identified, and appropriate decision support interventions should be developed and evaluated. PMID- 11206943 TI - Visual analog scales, standard gambles, and relative risk aversion. AB - BACKGROUND: It has been argued that visual analog scales (VASs) elicit an individual's measurable value function. The theoretical link between an individual's measurable value function v(.) and his or her von Neumann-Morgenstem utility function u(.) appears to provide a justification for transforming VAS scores into standard gamble (SG) utilities. However, VAS scores have been found to be subject to the effects of context, which casts doubt that the procedure is properly revealing v(.). METHODS: The authors tested for the effects of context on VAS and SG scores. They also explored whether the range-frequency (R-F) model of Parducci offers a means of correcting VAS scores for the effects of context. RESULTS AND CONCLUSIONS: The R-F model may provide a means of correcting VAS scores for the effects of context, but no stable relationship exists between these corrected scores and SG utilities. Hence, there remain no grounds for transforming VAS scores into SG utilities. PMID- 11206944 TI - Factors influencing physicians' judgments of adherence and treatment decisions for patients with HIV disease. AB - New medications for HIV reduce mortality and morbidity but require strict adherence. Thus, physicians treating HIV-positive patients must weigh both disease severity and likelihood of adherence when deciding whether to start patients on treatment. A national sample of 495 physicians surveyed via mail responded to clinical scenarios depicting HIV-positive patients and indicated whether they would start patients on medication (response rate = 53%). Scenarios varied on the patient characteristics of gender, disease severity, ethnicity, and risk group. Physicians predicted that patients with less severe disease, former injection drug users, and African American men would be less likely to adhere. Perceived adherence and disease severity influenced treatment decisions. Results are discussed in the context of attitudes about minority groups and injection drug users, which may influence adherence judgments in practice settings. Psychological research to identify better methods of predicting medication adherence may serve to inform medical decision making. PMID- 11206945 TI - General performance on a numeracy scale among highly educated samples. AB - BACKGROUND: Numeracy, how facile people are with basic probability and mathematical concepts, is associated with how people perceive health risks. Performance on simple numeracy problems has been poor among populations with little as well as more formal education. Here, we examine how highly educated participants performed on a general and an expanded numeracy scale. The latter was designed within the context of health risks. METHOD: A total of 463 men and women aged 40 and older completed a 3-item general and an expanded 7-item numeracy scale. The expanded scale assessed how well people 1) differentiate and perform simple mathematical operations on risk magnitudes using percentages and proportions, 2) convert percentages to proportions, 3) convert proportions to percentages, and 4) convert probabilities to proportions. RESULTS: On average, 18% and 32% of participants correctly answered all of the general and expanded numeracy scale items, respectively. Approximately 16% to 20% incorrectly answered the most straightforward questions pertaining to risk magnitudes (e.g., Which represents the larger risk: 1%, 5%, or 10%?). A factor analysis revealed that the general and expanded risk numeracy items tapped the construct of global numeracy. CONCLUSIONS: These results suggest that even highly educated participants have difficulty with relatively simple numeracy questions, thus replicating in part earlier studies. The implication is that usual strategies for communicating numerical risk may be flawed. Methods and consequences of communicating health risk information tailored to a person's level of numeracy should be explored further. PMID- 11206946 TI - Prognostic modeling with logistic regression analysis: in search of a sensible strategy in small data sets. AB - Clinical decision making often requires estimates of the likelihood of a dichotomous outcome in individual patients. When empirical data are available, these estimates may well be obtained from a logistic regression model. Several strategies may be followed in the development of such a model. In this study, the authors compare alternative strategies in 23 small subsamples from a large data set of patients with an acute myocardial infarction, where they developed predictive models for 30-day mortality. Evaluations were performed in an independent part of the data set. Specifically, the authors studied the effect of coding of covariables and stepwise selection on discriminative ability of the resulting model, and the effect of statistical "shrinkage" techniques on calibration. As expected, dichotomization of continuous covariables implied a loss of information. Remarkably, stepwise selection resulted in less discriminating models compared to full models including all available covariables, even when more than half of these were randomly associated with the outcome. Using qualitative information on the sign of the effect of predictors slightly improved the predictive ability. Calibration improved when shrinkage was applied on the standard maximum likelihood estimates of the regression coefficients. In conclusion, a sensible strategy in small data sets is to apply shrinkage methods in full models that include well-coded predictors that are selected based on external information. PMID- 11206947 TI - Health values and prospect theory: a comment. AB - In a recent volume of Medical Decision Making, Treadwell and Lenert stated that under prospect theory, community members compared with patients underestimate the utility of health improvements. In this comment, the authors show that this statement holds only for a subset of possible preference functions. Furthermore, the authors provide arguments that, in general, the rater's current health state is not the appropriate reference level if applying prospect theory to health valuations. PMID- 11206948 TI - The inclusion of patient testimonials in decision aids: effects on treatment choices. AB - BACKGROUND: Decision aids often provide statistical information and patient testimonials to guide treatment choices. This raises the possibility that the testimonials will overwhelm the statistical information. METHODS: Prospective jurors in Philadelphia County were presented with hypothetical statistical information about the percentage of angina patients who benefit from angioplasty and bypass surgery (50% and 75%, respectively). They were also given written testimonials from hypothetical patients who had benefited or not benefited from each of the two treatments. The numbers of patients benefiting and not benefiting were varied to be either proportionate to the statistical information or disproportionate. In study 1, all participants received 1 testimonial from a patient who had benefited from angioplasty and 1 from a patient who had not. Participants receiving the proportionate questionnaire version were also given 3 testimonials from patients who benefited from bypass surgery and 1 from a patient who did not, coinciding with the hypothetical statistical information. In contrast, participants receiving the disproportionate questionnaire version received only 1 testimonial from a patient who benefited from surgery and 1 from a patient who did not. In study 2, all participants received 2 examples of patients who benefited from angioplasty and 2 who did not. Participants with the proportionate questionnaire version received the same testimonials regarding surgery as in study 1. Those receiving the disproportionate questionnaire version received 2 testimonials from patients who benefited from bypass and 2 from patients who did not. Finally, a separate set of participants in study 2 received a questionnaire with no testimonials. RESULTS: In study 1, 30% of participants receiving the disproportionate questionnaire version chose bypass surgery versus 44% of those receiving the proportionate questionnaire (P = 0.002 by chi2). In study 2, 34% of participants receiving the disproportionate questionnaire version chose bypass surgery versus 37% of those receiving the proportionate questionnaire (P = 0.59 by chi2). Of those receiving no patient testimonials, 58% chose bypass surgery. CONCLUSIONS: The inclusion of written patient testimonials significantly influenced hypothetical treatment choices. Efforts to make the mix of positive versus negative testimonials proportionate to statistical information may, under some circumstances, affect choices in ways that cannot automatically be assumed to be optimal. PMID- 11206949 TI - A comparison of United Kingdom and Spanish general population time trade-off values for EQ-5D health states. AB - Few studies have compared preference values for health states obtained in different countries. The present study compared Spanish and United Kingdom (UK) time trade-off values for EuroQol-5D health states. The same preference elicitation protocol was followed in both countries. Differences in values for 43 health states rated directly were analyzed using t tests, and regression coefficients generated by random effects modeling were compared by aggregating the 2 value sets and using dummy variables to analyze country effect by dimension and level of severity. For the milder health states, Spanish and UK value assignation was similar; for intermediate health states, Spanish values were both higher and lower than UK values, whereas for health states worse than death, UK values were generally higher than Spanish values. There were statistically significant differences (P < 0.01) in values for 34.9% of health states rated directly, and some preference reversals between countries. UK raters ascribed greater importance to dimensions of pain/discomfort and anxiety/depression, whereas Spanish raters placed more importance on functional dimensions of mobility and self-care. Further analysis is required to determine how these differences affect cost-effectiveness and cost-utility analyses. PMID- 11206950 TI - Reflections on the beginnings and future of Medical Decision Making. PMID- 11206951 TI - Medical Decision Making: 20 years of advancing the field. PMID- 11206952 TI - The Society for Medical Decision Making at 21. PMID- 11206953 TI - A Society for Medical Decision Making. PMID- 11206954 TI - Law and ethics. PMID- 11206955 TI - On using the standard gamble to determine utilities for uncertain health states. PMID- 11206956 TI - Current issues with blood transfusions in sickle cell disease. AB - With increased recognition of the profound morbidity of sickle cell disease and with growing evidence of the efficacy of transfusion therapy in prevention and treatment of sickle cell complications, most patients now receive intermittent transfusion therapy. The purpose of this report is to review blood component therapy and Its risks for sickle cell patients. Packed red cells are the preferred blood component. Leukocyte-reduced units should be standard because of their beneficial effects in reducing alloimmunization, transfusion reactions, platelet refractoriness, and infection transmission. The use of washed, frozen, or Irradiated units is limited to specific problems. Sickle trait-positive units function normally, but because of difficulties with calculating hemoglobin S percentages and leukocyte filters, they are not routinely used. Transfusion acquired infections have shown a marked decrease but still present a major risk. Viral hepatitis transmission is currently low, but at least 10% of adult sickle cell patients are hepatitis C positive, and they often have liver damage. Although bacterial infections are rare, they account for 16% of transfusion related fatalities. Patients who are iron overloaded are particularly vulnerable to Yersina enterocolitica. Red cell alloimmunization is a serious problem that could potentially affect 50% of transfused patients. However, preventive phenotypic matching for common antigens can minimize alloimmunization; limited matching for at least E, C, and K has become the standard of care. Recently, more patients are being identified who have developed red cell autoantibodies, which can mask alloantibodies and occasionally are hemolytic. Careful laboratory evaluation of all cases is essential. Transfusions also may trigger sickle cell events, including pain crises, stroke, and acute pulmonary deterioration. In part, these are induced by blood viscosity and increased blood pressure. Diuretic therapy and close monitoring of transfusion volume and vital signs can minimize these events. In summary, transfusion therapy carries risks, but the routine use of leukocyte-reduced, phenotypically matched units in conjunction with close monitoring of patients can make transfusion therapy safer. PMID- 11206957 TI - Consensus document for transfusion-related iron overload. PMID- 11206958 TI - Techniques for blood administration in sickle cell patients. AB - Transfusion therapy provides many benefits to Individuals with sickle cell disease but may lead to cardiovascular complications, alloimmunization, exposure to infection, and iron overload. Simple transfusion is used to increase oxygen carrying capacity. Chronic simple transfusion is useful in preventing a number of complications in sickle cell disease. Acute erthrocyte exchange transfusion can reduce the percentage of cells containing sickle hemoglobin while decreasing volume overload and minimizing hyperviscosity. Chronic erythrocyte exchange transfusion reduces iron loading but Increases donor exposure. Directed odnation may reduce alloimmunization and exposure to infection. PMID- 11206959 TI - Iron overload is a determinant of morbidity and mortality in adult patients with sickle cell disease. AB - Patients with sickle cell disease (SCD) often require blood transfusion starting in early childhood. Multiple blood transfusions on a chronic basis lead to excessive accumulation of iron, especially in adults with sickle cell anemia (SS) that is progressively increasing in size. Blood exchange transfusion and the use of iron chelation therapy may prevent or delay the onset of iron overload. The majority of adults with SS, however, require episodic blood transfusions on a chronic basis and, hence, are at risk to develop iron overload. Recent reports suggest an association between iron overload and organ failure in chronically transfused patients. Patients with SCD and iron overload may thus be at increased risk to develop organ failure compared to those with normal iron stores. In order to clarify this issue we have prospectively collected the following data on our adult patients with SCD between 1978 and 1998: (1) the amount of blood transfused; and (2) the status of iron stores determined with serum ferritin, serum iron, total iron binding capacity (TIBC), and percent transferrin saturation (% Sat). Between 1987 and 1998, 247 adult patients with SS were regularly followed in our sickle cell center. Of these, 152 (62%) were transfused with 4,875 units of red blood cells (RBCs). Transfused patients received an average of 10 units of RBCs per year, which is equivalent to about 2.0 g of iron per year. This does not include transfusions at other institutions or before 1987. About one third of the adult patients with SS had % Sat greater than 50 in the steady state, suggesting iron overload. During painful episodes serum ferritin increased significantly in paired observations. Serum iron and TIBC decreased during painful episode disproportionately so that there was a significant net decrease in % Sat in paired observations. Patients with low values of serum ferritin and % Sat had lower incidence of acute painful episodes (38% v 64%) and organ failure (19% v 71%) than those who had iron overload, respectively. Mortality was significantly higher in the iron overload group: 64% versus 5%, respectively. Taken together, the data indicate that (1) the status of iron stores in adults with SS is best determined by keeping accurate records of the amount of blood transfused and serial determinations of ferritin levels in the steady state; (2) a significant number of adults with SS have iron overload; and (3) iron overload seems to be a predisposing factor of disease severity. PMID- 11206960 TI - Noninvasive methods for quantitative assessment of transfusional iron overload in sickle cell disease. AB - Because optimal management of iron chelation therapy in patients with sickle cell disease and transfusional iron overload requires accurate determination of the magnitude of iron excess, a variety of techniques for evaluating iron overload are under development, including measurement of serum ferritin iron levels, x-ray fluorescence of iron, magnetic resonance imaging, computed tomography, and measurement of magnetic susceptibility. The most promising methods for noninvasive assessment of body iron stores in patients with sickle cell anemia and transfusional iron overload are based on measurement of hepatic magnetic susceptibility, either using superconducting quantum interference device (SQUID) susceptometry or, potentially, magnetic resonance susceptometry. PMID- 11206961 TI - Indications for red cell transfusion in sickle cell disease. AB - Transfusion of red blood cells is an important therapeutic method employed in the care of people with sickle cell disease (SCD). There are several clinical situations in which patients with SCD clearly need red cell transfusion (RCT). In other situations, the indication for RCT is doubtful, controversial, or III advised. RCT is used on either an episodic or chronic basis in the management of SCD. Episodic transfusions are usually applied in a patient who has already developed a serious complication of SCD or are used to reduce the chances for the development of a complication. Chronic transfusion therapy is often used to prevent the recurrence of a major complication such as a stroke. Recently, chronic transfusion has been applied to patients with evidence of cerebrovascular disease to prevent the first occurrence of stroke. PMID- 11206962 TI - Progression of iron overload in sickle cell disease. AB - The expanding indications for transfusions in patients with sickle cell disease raise the issues of appropriate measurement of body iron burden and optimal timing of iron chelation therapy. In this study, we obtained 42 biopsy specimens from 20 patients with sickle cell disease (mean age, 15.7 years) who received transfusions. In 12 patients whose mean age was 11.3 years at the time of liver biopsy, hepatic iron concentration was measured to provide information about the rate of iron accumulation in sickle cell disease, as well as to guide the initiation of chelating therapy. Mean hepatic iron concentration after an average of 15.4 transfusions administered over 21 months was 9.4 +/- 1.2 mg/g liver, dry weight, which did not correlate significantly with determinations of serum transferrin or ferritin levels. On Initial liver biopsy, hepatic portal fibrosis was noted in 4 of 12 patients. Twenty-nine biopsies in 16 patients were performed after variable periods of treatment with deferoxamine. These 16 patients had received a mean of 38.5 transfusions over 4 years. Hepatic iron was 14.1 +/- 1.9 mg/g of liver, dry weight, Indicating poor control of body iron in many patients. Cirrhosis was reported in one of 29 and portal fibrosis in 10 biopsy specimens. Hepatic iron concentration in patients in whom fibrosis was observed varied from 8.9 to 37.7 mg/g of liver, dry weight. These data show that after 1 to 2 years of conventional transfusions, variable tissue iron concentrations and tissue damage are observed in patients with sickle cell disease. In some patients, iron chelation therapy may not be appropriate after 1 year of transfusions; in others, therapy is clearly indicated by this time to prevent tissue injury. The data also suggest that patients with sickle cell disease develop increased portal fibrosis at the thresholds previously described in young patients with thalassemia (approximately 7 mg/g of liver, dry weight). PMID- 11206963 TI - Deferoxamine pharmacokinetics. AB - Despite the clinical use of deferoxamine for more than a quarter of a century, pharmacokinetic studies are few and have not been performed explicitly in patients with sickle cell disorders. Early studies with Intravenous administration to healthy volunteers and patients with transfusional overload showed that although peak concentrations of deferoxamine were similar in both groups, concentrations of ferrioxamine were higher in the latter. In iron overloaded patients with hereditary hemochromatosis, an intramuscular 10 mg/kg bolus of deferoxamine gave maximal plasma ferrioxamine concentrations exceeding those of deferoxamine, whereas in normal controls the reverse was the case. In more recent studies with homozygous beta-thalassemia, using continuous Intravenous deferoxamine infusion at 50 mg/kg/d, and initial elimination half life of 0.28/h and steady-state concentration of 7 micromol/L were observed. In these studies, steady-state plasma levels of the predominant deferoxamine metabolite B were usually lower than those of unmetabolized deferoxamine. In a further intravenous infusion study, the proportion of plasma metabolites was higher in those thalassaemia patients with low serum ferritin levels relative to their current mean daily deferoxamine dose, suggesting that high metabolite levels may predict excessive desferrioxamine dosing. This hypothesis is supported by subcutaneous studies in which low doses of slow-release depot deferoxamine resulted in significantly lower proportions of plasma metabolites than with conventional 8-hour infusions at 40 mg/kg. Because serum ferritin is particularly unreliable as a marker of iron overload in sickle cell disorders, measurement of metabolites or the relative proportions of deferoxamine and ferrloxamine may help identify patients at risk of excessive dosing. Because iron overload is likely to become an increasing issue in patients with sickle cell disorders, studies of the pharmacokinetics and metabolism of deferoxamine in this patient group are needed. PMID- 11206964 TI - Iron chelation therapy in sickle cell disease. AB - Iron chelation therapy with deferoxamine enhances iron excretion and removes excessive tissue iron in regularly transfused patients with sickle cell disease. Long-term studies of deferoxamine in other hemoglobinopathies demonstrate that regular chelation therapy also reduces iron-related organ damage and mortality. Careful design of chelation regimens and attention to compliance are critical elements of successful therapy. The role of new chelators in sickle cell disease is currently under Investigation. PMID- 11206965 TI - Iron chelation: new therapies. AB - Iron chelators are used in clinical practice to protect patients from the complications of iron overload and iron toxicity because there is no physiologic way for excess iron to be actively excreted. Deferoxamine, the only iron chelating agent available for clinical use in the United States, is administered as a prolonged (8 to 24 hours) infusion, leading to poor compliance in many patients. Although many compounds have been screened in tissue cultures and animals as iron chelators, few have reached the stage of phase I and II clinical trials. The search for new chelating agents, which includes the "slow-release" depot formulation of deferoxamine and the "long-acting" hydroxyethyl starch deferoxamine, has been disappointing because clinical trials have not demonstrated the intended efficacy. A more promising compound, ICL 670A--an orally active representative of a new class of iron chelators designed by computer modeling-is a potent and selective iron chelator. Its ability to mobilize tissue iron and promote its excretion has been shown in several animal models. In phase I dose-finding trials, ICL 670A was well tolerated and had a good safety profile. This compound is currently undergoing further clinical evaluation. PMID- 11206966 TI - Improving adherence with deferoxamine regimens for patients receiving chronic transfusion therapy. AB - We designed a study to obtain follow-up on behavioral aspects of compliance with home deferoxamine administration, explore social factors that might influence compliance, and evaluate the effectiveness of a pilot intervention program for patients with thalassemia or sickle cell disease who were receiving chronic transfusion therapy. Thirty-one patients between the ages of 6 and 21 years and their primary caregivers were administered a 24-hour recall Interview about home care. Fifteen went on to participate in a Desferal Day Camp, which combined educational strategies with peer support. Behavioral measures of treatment adherence were similar for most patients with sickle cell disease and thalassemia. Patient compliance with days of deferoxamine administration at follow-up was associated with initial compliance, perceived support, and patient and caregiver knowledge. Increased sharing of responsibilities for home care by patients and caregivers and caregiver knowledge were associated with lower ferritin and liver iron levels. A subsample of 3 patients who were extremely noncompliant with days of deferoxamine administration was examined separately; these patients were found to be moderately compliant with the number of hours and amount of deferoxamine administered and to share fewer home care tasks with primary caregivers. Participation in Desferal Day Camp did not result in increases in knowledge or peer support, suggesting that future interventions should focus on family support and on improving self-regulatory skills. The crucial role of collaboration among patients, families, and health care providers in developing interventions to enhance adherence was emphasized. PMID- 11206967 TI - Plant tubulins: a melting pot for basic questions and promising applications. PMID- 11206968 TI - A new gene trap construct enriching for insertion events near the 5' end of genes. AB - The gene trap approach is based on the integration of a gene trap vector into the genome. This can be done either by electroporation of a plasmid construct or by infection with a viral vector. Commonly used viral gene trap vectors have been shown to select for integrations near the 5' end of genes. To date, no plasmid vector with a similar tendency has been reported. In this paper we describe a new plasmid vector, pKC199beta geo. This vector contained a short splice acceptor fragment from the Hoxc9 gene, a full length lacZ gene, including an ATG, and a reduced activity, mutant neomycin phosphotransferase gene as a selectable marker. This vector enriched the population of trapped genes in our gene trap screen for insertion events in the 5' end of genes. In the two cases examined the beta galactosidase activity pattern accurately reflected the endogenous promotor activity. PMID- 11206969 TI - Efficient production of transgenic cassava using negative and positive selection. AB - In order to improve the efficiency of cassava (Manihot esculenta Crantz) transformation, two different selection systems were assessed, a positive one based on the use of mannose as the selective agent, and a negative one based on hygromycin resistance encoded by an intron-containing hph gene. Transgenic plants selected on mannose or hygromycin were regenerated for the first time from embryogenic suspensions cocultivated with Agrobacterium. After the initial selection using mannose and hygromycin, 82.6% and 100% of the respective developing embryogenic callus lines were transgenic. A system allowing plant regeneration from only transgenic lines was designed by combining chemical selection with histochemical GUS assays. In total, 12 morphologically normal transgenic plant lines were produced, five using mannose and seven using hygromycin. The stable integration of the transgenes into the nuclear genome was verified using PCR and Southern analysis. RT-PCR and northern analyses confirmed the transgene expression in the regenerated plants. A rooting test on mannose containing medium was developed as an alternative to GUS assays in order to eliminate escapes from the positive selection system. Our results show that transgenic cassava plants can be obtained by using either antibiotic resistance genes that are not expressed in the micro-organisms or an antibiotic-free positive selection system. PMID- 11206970 TI - Copy number related transgene expression and mosaic somatic expression in hemizygous and homozygous transgenic tilapia (Oreochromis niloticus). AB - Three lines of transgenic tilapia (Oreochromis niloticus) fish were generated with a construct containing a lacZ reporter gene spliced to a 4.7 kb 5' regulatory region of a carp beta actin gene. All these three lines contain different copy numbers of transgenes and the levels of lacZ expression were found to be related to transgene copy number. Mosaic patterns of somatic lacZ expression were observed in these three lines which differed between lines but were consistent within a line. We also observed that expression of the reporter gene in homozygous transgenic fish was approximately two-fold greater than in the hemizygous transgenics. Analysis of expression of the reporter gene on a tissue to-tissue basis demonstrated that lacZ expression of the reporter gene in stably transformed fish occured with variable intensity in different organs and tissues and was also sometimes variable in different cells of the same tissue in Gland G2 generations of the transgenic lines. PMID- 11206971 TI - Constitutive expression of interferon-induced human MxA protein in transgenic tobacco plants does not confer resistance to a variety of RNA viruses. AB - MxA is a key component in the interferon-induced antiviral defense in humans. After viral infections, MxA is rapidly induced and accumulates in the cytoplasm. The multiplication of many RNA viruses, including all bunyaviruses tested so far, is inhibited by MxA. These findings prompted us to express MxA in plants in an attempt to create resistance to tospoviruses. Here, we report the generation of transgenic tobacco plants that constitutively express MxA under the control of the 35 S cauliflower mosaic virus promotor. Northern and western blot analysis confirmed the expression of MxA in several transgenic plant lines. MxA expression had no obvious detrimental effects on plant growth and fertility. However, challenge experiments with tomato spotted wilt virus, tomato chlorotic spot virus, and groundnut ringspot virus revealed no increased resistance of MxA transgenic tobacco plants to tospovirus infections. Neither was the multiplication of tobacco mosaic virus, cucumber mosaic virus and potato virus Y inhibited in MxA-transgenic plants. The results indicate that the expression of human MxA alone does not enhance virus resistance in planta. PMID- 11206972 TI - Deletion of the gene encoding H-FABP/MDGI has no overt effects in the mammary gland. AB - Heart fatty acid binding protein (H-FABP) is expressed abundantly in the mammary gland. A number of in vitro studies have shown that H-FABP is functionally indistinguishable from a factor isolated from this organ, termed mammary derived growth inhibitor (MDGI), which specifically inhibits the proliferation of mammary tissue. We have previously shown that over-expression of H-FABP/MDGI in the mammary gland of transgenic mice has no discernable effects on cell proliferation or differentiation. In this report we describe knockout mouse in which the H FABP/MDGI gene has been specifically disrupted. The mice exhibit no overt phenotype in the mammary gland, and we conclude that this gene does not play a specific role in regulating the normal development or function of this tissue. PMID- 11206973 TI - Constitutive expression of soybean ferritin cDNA in transgenic wheat and rice results in increased iron levels in vegetative tissues but not in seeds. AB - We used particle bombardment to produce transgenic wheat and rice plants expressing recombinant soybean ferritin, a protein that can store large amounts of iron. The cDNA sequence was isolated from soybean by RT-PCR and expressed using the constitutive maize ubiquitin-1 promoter. The presence of ferritin mRNA and protein was confirmed in the vegetative tissues and seeds of transgenic wheat and rice plants by northern and western blot analysis, respectively. The levels of ferritin mRNA were similar in the vegetative tissues of both species, but ferritin protein levels were higher in rice. Both ferritin mRNA and protein levels were lower in wheat and rice seeds. ICAP spectrometry showed that iron levels increased only in vegetative tissues of transgenic plants, and not in the seeds. These data indicate that recombinant ferritin expression under the control of the maize ubiquitin promoter significantly increases iron levels in vegetative tissues, but that the levels of recombinant ferritin in seeds are not sufficient to increase iron levels significantly over those in the seeds of non-transgenic plants. PMID- 11206975 TI - Isogenic transgenic homozygous fish induced by artificial parthenogenesis. AB - As a model system for vertebrate transgenesis, fish have many attractive advantages, especially with respect to the characteristics of eggs, allowing us to produce isogenic, transgenic, homozygous vertebrates by combining with chromosome-set manipulation. Here, we describe the large-scale production of isogenic transgenic homozygous animals using our experimental organism, the mud loach Misgurnus mizolepis, by the simple process of artificial parthenogenesis in a single generation. These isogenic fish have retained transgenic homozygous status in a stable manner during the subsequent 5 years, and exhibited increased levels of transgene expression. Furthermore, their isogenic nature was confirmed by cloned transgenic homozygous offspring produced via another step of parthenogenic reproduction of the isogenic homozygous transgenic fish. These results demonstrate that a combination of transgenesis and artificial parthenogenesis will make the rapid utilization of genetically pure homozygous transgenic system in vertebrate transgenesis possible. PMID- 11206974 TI - Overexpression of the calcium-dependent protein kinase OsCDPK2 in transgenic rice is repressed by light in leaves and disrupts seed development. AB - Independent transgenic rice lines overexpressing the rice CDPK isoform OsCDPK2 were generated by particle bombardment. High levels of OsCDPK2 were detected in leaves removed from etiolated plants, as well as in stems and flowers. However, there was no overexpression in green leaves that had been exposed to light, confirming that OsCDPK2 protein stability was subject to light regulation. The morphological phenotype of transgenic plants producing high levels of recombinant OsCDPK2 was normal until the onset of seed development. Flowers developed normally, producing well-shaped ovaries and stigmas, and mature anthers filled with pollen grains. However, seed formation in these plants was strongly inhibited, with only 3-7% of the flowers producing seeds. Seed development was arrested at an early stage. We discuss these data with respect to the possible requirement for specific CDPK isoforms during rice seed development. PMID- 11206976 TI - Floral spray transformation can efficiently generate Arabidopsis transgenic plants. AB - In this study, floral spray and floral dip were used to replace the vacuum step in the Agrobacterium-mediated transformation of a superoxide dismutase (SOD) gene into Arabidopsis. The transgene was constructed by using a CaMV 35S promoter to drive a rice cytosolic CuZnSOD coding sequence in Arabidopsis. The transgene construct was developed in binary vectors and mobilized into Agrobacterium. When Arabidopsis plants started to initiate flower buds, the primary inflorescence shoots were removed and then transformed by floral spray or floral dip. More than 300 transgenic plants were generated to assess the feasibility of floral spray used in the in planta transformation. The result indicates that the floral spray method of Agrobacterium can achieve rates of in planta transformation comparable to the vacuum-infiltration and floral dip methods. The floral spray method opens up the possibility of in planta transformation of plant species which are too large for dipping or vacuum infiltration. PMID- 11206977 TI - Active expression of the ubiA gene from E. coli in tobacco: influence of plant ER specific signal peptides on the expression of a membrane-bound prenyltransferase in plant cells. AB - The ubiA gene from E. coli codes for 4-hydroxybenzoate: polyprenyldiphosphate 3 polyprenyltransferase, an integral membrane protein involved in ubiquinone biosynthesis. This prokaryotic membrane protein was stably expressed in tobacco using Agrobacterium tumefaciens-mediated transformation. Transgenic lines containing a direct fusion of the ubiA structural gene to a 35S-derived promoter gave very low enzyme activity levels (average 0.16 pkat/mg). Inclusion of an N terminal ER-specific signal peptide from a lectin gene from Phaseolus vulgaris resulted in an average activity of 1.08 pkat/mg in the transgenic tobacco lines. The additional inclusion of a C-terminal HDEL tetrapeptide, responsible for the retention of proteins in the endoplasmic reticulum of eukaryotic cells, increased the activity to 18.6 pkat/mg. When the promotor of this construct was changed from the 35S derivative to the recently described very strong plant promoter (ocs)3mas, the activity increased further to 128.6 pkat/mg. The most active tobacco line showed activities of the introduced enzyme which exceeded those of wild-type E. coli (the source of ubiA) by a factor of 1100. These results demonstrate the efficacy of plant ER-specific signal peptides for the active expression of a prokaryotic membrane protein in plants. PMID- 11206978 TI - Molecular farming-OECD workshop. Organisation for Economic Cooperation and Development. PMID- 11206979 TI - Effects of hyaluronic acid on the morphology and proliferation of human chondrocytes in primary cell culture. AB - Hyaline articular cartilage is a specialised connective tissue with weight bearing and adsorbing functions. Injury or loss of which often leads to impaired joint function and severe pain. Since the self-renewing abilities of hyaline articular cartilage are limited, there is major interest in the development of bioengineered cartilaginous implants. A cell-matrix-biocomposite composed of a collagen I/III scaffold seeded with autologous chondrocytes is currently being used in clinical trials; however, in order to optimise culture conditions, we cultured human condrocytes and seeded them on type I/III collagen membranes and on Thermanox plastic coverslips with media containing 0 to 500 microg/ml Hyaluronic Acid. After 4 days, the cells were either fixed or BrdU incorporation procedures begun. HE staining clearly demonstrated that cells grown in HA form three dimensional clusters and produce secretory vesicles as opposed to the monolayer control cells with noticeably fewer secretory vesicles. BrdU incorporation revealed a noticeable increase in cell proliferation in cells grown in 100 microg/ml; however, no comparable increase in 500 micorg/ml but rather a slight depression in proliferation. Immunohistochemistry for collagen II and aggrecan revealed an obvious increase in deposition of these two substances with increased HA administration as compared to the control; however, again, the higher concentration of HA, 500 microg/ml, did not result in a further increase in production. These results suggest that HA at 100 microg/ml not only influences chondrocytes to differentiate and produce more Collagen II and aggrecan, but also increases proliferation. We, therefore, propose that the addition of HA at low to middle dosages in condrocyte culturing might help improve condrocyte redifferentation and thus, the bioengineered cartilage. PMID- 11206980 TI - Functional and angioarchitectural structure and classification of lingual papillae on the postero-dorsal surface of the beagle dog tongue. AB - A scanning electron microscopic study was done of the three-dimensional, morphological structure and classification by means of microvascular cast specimens (MVCS) of the filiform (FiP), fungiform (FuP) and circumvallate papillae (CvP) on the postero-centro-peripheral, and conical papillae (CoP) on the posteroperipheral-dorsal surface of the caudal portion of the beagle dog tongue. The characteristics and functional arrangement of each lingual papilla were as follows: the FiP densely and geometrically covered the entire postero centro-peripheral dorsal surface. The outer structure of the FiP, consisting of both the ascending and descending branches from their tributaries, was a spoon like capillary micro-network structure with a sharp arrowhead-like top inclined posteriorly. On the other hand, the outer structure of the FuP, appearing sporadically on the oblique lines of the FiP, was of round form consisting of a capillary microvascular network structure. The FuP, consisting of ascending and descending branches similar to the FiP, were distributed sporadically and geometrically on oblique lines in a V-form running from both peripheral sides to postero-central direction on the FiP A group of three CvPs were arranged on oblique lines in a V form from the peripheral to the postero-central region on the postero-dorsal surface. The outer shape of the microvascular network structure of the CvP was a round fence-like structure surrounding the papillary body and the papillary body consisted of an inner semi-spherical microvascular network structure. The CoP densely covered the entire postero-peripheral-dorsal surface. The exterior figure of the conical micro-network structure, consisting of both the ascending and descending branches of the CoP, was a cone-like capillary network structure, and the sharp tops were inclined posteriorly. They were classified into three types: large (L-CoP), medium (M-CoP) and small (S-CoP) according to the morphological characteristics in shape, size and the distributive position. It was conjectured that the FiP play a concentric functionally important role in transporting food and liquid from both sides in a postero-central direction towards the pharynx. And, on the other hand, the FuPs play an assistant role in receiving gustatory sensations from the masticated food and liquid on the central dorsal surface. The CoP play a functionally important role on the postero-peripheral-dorsal surface, in transporting food and liquid towards the pharynx and a complementary role of the CvP is to receive gustatory sensations from masticated food and liquid on the postero-peripheral-dorsal surface of the caudal portion of the beagle dog tongue. PMID- 11206981 TI - The secondary tongue of Salamandra salamandra: histochemical and ultrastructural aspects of the developing lingual epithelium. AB - The development of the lingual epithelium of Salamandra salamandra was investigated with emphasis on histochemical and ultrastructural aspects. The temporal and spatial occurrence and the typical appearance of various cell types; i.e. pavement cells, replacement pavement cells, basal cells, mitochondria rich cells, goblet cells and glandular cells have been analysed and documented in detail from the young larval stage up to the metamorphosed animal (2 months after metamorphosis). It is shown that anatomical re- and de novo-constructions related to the formation of the secretory tongue led to distinct changes in the cellular equipment of the epithelium of the tongue, including various histochemical properties. Finally, functional aspects of the morphological characteristics are discussed in detail and compared with respective findings in other species. PMID- 11206982 TI - The development of the tooth pattern and dentigerous bones in Polypterus senegalus (Cladistia, Actinopterygii). AB - The formation sequence of the tooth-bearing bones and the tooth pattern in early ontogeny of Polypterus senegalus is investigated using transparent preparation, histological sections, and SEM. During the attachment step of the yolk-sac larva the first dermal bones and teeth are formed. Teeth appear simultaneously in the areas of the maxillary, dentary, dermopalatine, prearticular, and coronoid 1 along with the first separate anlagen of these bones. A monostichous arrangement of primary teeth is established on the maxillary, dentary, and dermopalatine. Polystichous tooth arrangements do not occur before the early pterolarval phase, and then only in connection with bones of the palate and inner dental arcades. Especially pronounced is the influence of tooth formation on the structure of the parasphenoid that becomes much thickened by accretion of denticulate platelets, but we found neither evidence for a distinct vomeral contribution to the parasphenoid, nor a composite origin of the ectopterygoid in ontogeny. First replacement teeth are found in association with the maxillary and dentary as early as the late apterolarval phase. Primary teeth are of a single general type, whereas from the pterolarval phase onward three tooth types can be distinguished that are restricted to certain tooth bearing bones. Relatively late in ontogeny, dermo-metapterygoid and entopterygoid become formed and colonised by teeth, whereas first branchial teeth and tooth plates appear earlier during the first phase of extrinsic larval feeding. Characteristics of development of the dentition are discussed in comparison with character states of other better known fossil and recent taxa among Actinopterygii and Sarcopterygii. Compared to the assumed basic pattern of actinopterygian fishes, Polypteriformes show a derived condition with respect to structure, arrangement, replacement, and differentiation of teeth, which arises in sequence during larval development. This also corresponds to observed changes of feeding behaviour and functional demands during larval life. PMID- 11206983 TI - Anatomical composition of the anterior shoulder joint capsule. A cadaver study on 12 glenohumeral joints. AB - Twelve right cadaver shoulder joints were investigated after alcohol-formalin glycerol fixation. The tendons of the "rotator cuff" were separated from the joint capsule. The capsulo-ligamentous structures: Lig. coracohumerale, Lig. coracoglenoidale and Ligg. glenohumeralia were dissected. In addition to the Ligg. glenohumerale superius, medium et inferius, an "unknown glenohumeral ligament" coursed in the midline of the superficial layer of the anterior shoulder joint capsule. It arose from the axillary part of the Lig. glenohumerale inferius and the insertion tendon of the Caput longum m. tricipitis brachii, coursed upwards laterally and fused with the Lig. glenohumerale medium. Between the Ligg. glenohumerale medium et inferius it was connected with the shoulder joint capsule by loose connective tissue. Craniolaterally it melted into the superior portion of the M. subscapularis and inserted together with its tendon to the Tuberculum minus of the Humerus. The ascending fibres of the "unknown glenohumeral ligament" and the oblique, descending fibres of the Ligg. glenohumeralia medium et inferius crossed twice and formed X-shape connections between the ligaments. In external rotation and abduction or anteversion the course of fibres of the "unknown glenohumeral ligament" was spiral. According to the shape and anatomical position of the "unknown glenohumeral ligament" we propose to name it "Lig. glenohumerale spirale". PMID- 11206984 TI - Development of the membranous labyrinth of human embryos and fetuses using computer aided 3D-reconstruction. AB - The last detailed description of the development of the inner ear membranous labyrinth goes back to Streeter in 1918. This investigation can be regarded to be of outstanding scientific value. However, at that time no staging system of human embryos existed. In this respect, Streeter's work is outdated. It was the aim of this study to reinvestigate the development of the membranous labyrinth in human embryos and fetuses of which the developmental stages have been determined according to the Carnegie staging system and to compare the results with the literature. Serial histologic sections in the coronal or frontal plane of the heads of human embryos and fetuses of different developmental stages were used for computer aided 3D-reconstruction of the membranous labyrinth. From the obtained results, it is concluded that the endolymphatic duct develops earlier than previously described in the literature. The induction of the differentiation of the endolymphatic duct does not correspond with the superficial ectoderm because the endolymphatic duct develops medial of the otic vesicle. The membranous labyrinth determines the form of the petrosal bone as early as in stage 19 (47-48 days post conception). PMID- 11206985 TI - 3D-reconstruction of craniofacial structures of a human anencephalic fetus. Case report. AB - It was the purpose of this study to investigate the craniofacial bones, cartilages and major blood vessels of a human anencephalic fetus and to describe the malformations of these structures accompanying this developmental disruption. The head of a 16 week old human fetus with anencephaly was serially sectioned and the craniofacial bones, cartilages and major blood vessels were traced and reconstructed by 3D-computer technology. The sphenoidal, temporal and occipital bones showed severe malformations, whereas the bones of the facial cranium were normally developed. Both internal carotid arteries ended within the cerebro vascular area with no further branches. The vertebral arteries also ended within the cerebro-vascular area. No arterial circle of Willis was developed. The notochord terminated normally in the sphenoid body. The observations indicate that the possible reason for this malformation was non-closure of the anterior neuropore of the neural tube. The normal termination of the notochord suggests that it had no influence on the pathogenesis of this malformation. The malformations of the temporal and occipital bones are contradictory to the hypothesis of Marin-Padilla (1991) that anencephaly is caused by a maldevelopment of the sphenoidal bone. PMID- 11206986 TI - Osteological investigations of the incidence of cranial alterations in domestic ducks (Anas platyrhynchos f. dom.) with feather crests. AB - The feather crest of the domestic duck (Anas platyrhynchos f. dom.) represents a peculiar mutation of the integument of the head, which has been known since the 17th century. In literature this is described as a variety with malformations in skull and brain anatomy in which various central nervous deficiencies in affected birds are possible. Our examinations demonstrated several conspicuous anatomical alterations in the skulls of domestic ducks with feather crests. Osteophytes of different size in the hypodermis of the crest integument were found as well as cranial perforations located in the parieto-occipital region. In morphometric studies, a significant increase in the capacity of the cranium was found in Crested ducks compared to other examined breeds (Abacot Ranger, German Pekin ducks). This increase in cranial capacity in Crested ducks results from the occurrence and enlargement of a tentorial fatty depot during craniogenesis. The formation and enlargement of the fat body can influence cranium growth as long as the cranial bones are not entirely fused. Thus, in comparison to other phenotypically similar domesticated birds like the crested chicken, the expression of feather crests in domestic ducks demonstrates symptomatologic differences. In conclusion, our examinations demonstrate that the skulls of Crested ducks show various peculiar morphological alterations whose genesis is up to now not known with satisfactory accuracy. Further investigations are continuing to assertain whether there are linkages between cranial alterations (malformations of the calvaria, osteophytes, increased capacity of the cranium) and the extremely high prenatal and postnatal mortalities and numerous abnormalities described in crested breeds of the domestic duck. PMID- 11206987 TI - Musculoskeletal system of the neck of the polar bear (Ursus maritimus) and the Malayan bear (Helarctos malayanus). AB - The gross anatomical study was undertaken in the musculoskeletal system of the neck of the polar bear, and the findings were compared with those of the Malayan bear. The Musculus splenius and the M. trapezius were well-developed in the polar bear. The long neck of the polar bear consisted mainly of the M. splenius with the M. biventer cervicis and the M. complexus lying tightly underneath. The cervical vertebrae possessed huge ventral tubercle in the ventral part of the transverse process in the polar bear. These morphological characteristics suggest that the polar bear may rotate and bend the skull and the long cervical vertebrae. We postulate that the polar bear has evolved the high-mobility long neck to adapt for swimming. Unlike the polar bear, the Malayan bear has not specialized in the neck structure. PMID- 11206988 TI - Lack of inferior thyroid artery. AB - In the present study, a case of a cadaver is reported in which variations of some branches of both subclavian arteries occur. Among the most impressive findings is the lack of the right inferior thyroid artery combined with an abnormal ramification of the right superior thyroid artery, the terrace-like course of the left inferior thyroid artery and variations in the course of the prevertebral segment of both vertebral arteries with a high entry into the transverse cervical foramen of one of them. A morphometric description of the arterial variations has been carried out and their possible significance for the surgical and diagnostic practice is outlined. PMID- 11206989 TI - A modified Spalteholz technique with preservation of the histology. AB - The Spalteholz technique for producing clear macroscopic specimens was introduced 100 years ago, and is still in use today because it immediately provides transparent three-dimensional specimens. The classical clearing procedure with peroxide severely damages formalin-fixed tissue and inhibits further investigation on a histological level. We, therefore, wanted to make a transparent specimen by a modified Spalteholz method and chose the human larynx as an example of a large specimen. Its blood vessels were injected with gelatin, the specimen treated with acetone and peracetic acid and subjected to freeze substitution. After complete dehydration, benzyl benzoate and dimethylphthalate were used for impregnation. The cleared specimen satisfactorily revealed the laryngeal blood vessels and such structures as muscles, cartilage and the thyroid gland. The histology of the laryngeal glands, thyroid tissue, and infrahyoid muscle fibres was preserved. Tissue shrinkage became apparent with subsequent steps of the clearing procedure. We conclude that our modifications maintain the transparency of the specimen and allow histological investigation. The herein described technique thus constitutes an improvement of the classical Spalteholz technique. PMID- 11206990 TI - Re: "Cancer incidence near radio and television transmitters in Great Britain. I. Sutton Coldfield transmitter; II. All high power transmitters". PMID- 11206991 TI - Severe syndrome of inappropriate antidiuretic hormone secretion with docetaxel treatment in metastatic breast cancer. PMID- 11206992 TI - Lise Meitner and Niels Bohr--a historical note. PMID- 11206993 TI - Palliative medicine--a research challenge. PMID- 11206994 TI - Palliative care--past and future--questioning great expectations. AB - This paper argues that the future of palliative care cannot be divined reliably without considering how a set of basic questions might be answered by health-care professionals, administrators of health care systems, and citizens in countries throughout the world. Seven of the many questions centering on the mission of palliative care are explored here as pathways into the future of how we care for gravely ill and dying people. That future cannot be predicted from the vantage point of some super observatory. It will rather emerge from the responses we give now to a range of questions such as the seven considered in this paper. These questions identify fundamental dimensions of the mission of palliative care, and our responses will determine when, and where that mission will become reality. PMID- 11206995 TI - Psychosocial aspects in palliative care--communicating with the patient and family. AB - The dynamics surrounding the patient and family facing a death as the 'unit of care' is discussed. Aspects of communication, openness within the family, especially concerning children and teenagers, and factors that enable a family to function under the stress of a loved one's terminal illness are explored. The use of a genogram in palliative care to help to piece together the family dynamics and available support is fundamental to the care for the whole family. PMID- 11206996 TI - Qualitative research methods in palliative medicine and palliative oncology--an introduction. AB - Qualitative research methods can be used as a complement to quantitative methods in palliative research. Possible applications are 1) for the induction of hypotheses, 2) for the development of quality-of-life instruments, 3) for the exploration of complex phenomena and personal experiences, 4) for studying attitudes, 5) for the observation of interactions and 6) for validation of quantitative results. Depending on the context and the research question, different qualitative methods such as hermeneutics, phenomenology, grounded theory or phenomenography might be used. The assumptions, the main steps and the methods are briefly described, with some examples from palliative situations. PMID- 11206997 TI - Cancer patients' perceptions of their participation and own resources after receiving information about discontinuation of active tumour treatment. AB - The focus of most studies on informational needs has been on primary cancer diagnosis. The aim of this study was to explore how cancer patients in a palliative care setting perceived their own participation and resources after receiving information about the discontinuation of active tumour treatment. Thirty cancer patients admitted to a hospital-based home-care unit participated in the study. Semi-structured interviews were conducted and analysed using a phenomenographic method. The patients described their own participation as being either verbally passive or active, in order to receive more information or to avoid information. Furthermore, previous knowledge, at different levels, was described as important: 1) Unsuspecting naive, 2) apprehensive suspicious, 3) well prepared. Patients' own resources included a sense of wellbeing, a sense of security and individual strength. In conclusion, patients' previous knowledge and own resources are important components for their capacity to take part in the dialogue when receiving information. PMID- 11206998 TI - Are mobile phones harmful? AB - There is increasing public interest in health risks of mobile phone use. Although there is a vast body of material on the biological effects of radiofrequency fields, current risk assessment is still limited. The article describes several hypotheses and results of biological effects such as thermal effect, genetic and carcinogenic effects and cancer related investigations. Mobile phones transmit and receive waves of frequencies mainly at 800-1800 MHz. Findings on the thermal effect of acute exposure to radiofrequency fields were consistent, resulting in an increase of cellular, tissue or body temperature by 1 degree C or more. Guidelines for risk limits are based on this thermal effect. Experimental investigation suggests that radiofrequency fields are not tumor initiators and that if they are related to carcinogenicity, this would be by tumor promotion or by increasing the uptake of carcinogens in cells. Implications of these experimental results on public health concerns are yet unclear. Few epidemiological studies are available on the use of mobile phones or on the radiofrequency exposure and the development of cancer. Most of these studies have no or little quantitative exposure data and they are limited by the small number of observations. Large epidemiological studies are necessary in order to investigate the use of mobile phones on the development of cancer. It should be emphasized that even a small elevated risk may have a large implication for public health, as the use of mobile phones and the exposure is rapidly increasing. PMID- 11206999 TI - Maspin--a novel protease inhibitor with tumor-suppressing activity in breast cancer. AB - Maspin (mammary serpin) is a novel serine protease inhibitor related to the serpin family with a tumor-suppressing function in breast cancer. Maspin was originally identified from normal mammary epithelium by subtractive hybridization and might function as a class II tumor-suppressor gene. Maspin's decreased expression with increased level of malignancy and its loss in metastatic cells is regulated at the transcriptional level. Cytosin methylation and heterochromatinization in the promoter region might account for this down regulation of maspin. Transfection of tumor cells with maspin cDNA inhibits invasion and motility and decreases tumor growth and metastatic ability in nude mice. Maspin interacts with the p53 tumor-suppressor pathway and function as an inhibitor of angiogenesis in vitro and in vivo. The progressive loss of expression of maspin during tumor progression makes this new protein an interesting diagnostic and prognostic marker. The re-expression of maspin by pharmacological intervention potentially offers a promising approach as a therapeutic option in breast cancer therapy. PMID- 11207000 TI - Follow-up after primary treatment for breast cancer. AB - Follow-up after primary treatment for breast cancer is a routine practice aiming at early detection and management of local recurrences and/or distant metastases of the disease or of new primaries. Breast self-examination and periodic physical examination, mammography, and pelvic examination are the most important methods in following-up these patients. The, at one time, more popular intensive routine diagnostic evaluation (including head, chest, abdominal, and pelvic computerized tomography and/or magnetic resonance imaging, liver ultrasonography, bone scans, tumor markers, etc.) is not currently considered appropriate and cost-effective. However, flexibility, based on clinical judgement, is required on the part of medical staff involved in the follow-up in order appropriately to adapt the general guidelines and meet the specific needs of the individual patients. Non specialist or non-physician models of follow-up care have been proposed as interesting and cost-effective alternatives in the follow-up of breast cancer patients. PMID- 11207001 TI - Morphine or oxycodone in cancer pain? AB - Oxycodone is an opioid analgesic that closely resembles morphine. Oxymorphone, the active metabolite of oxycodone, is formed in a reaction catalyzed by CYP2D6, which is under polymorphic genetic control. The role of oxymorphone in the analgesic effect of oxycodone is not yet clear. In this study, controlled-release (CR) oxycodone and morphine were examined in cancer pain. CR oxycodone and morphine were administered to 45 adult patients with stable pain for 3-6 days after open-label titration in a randomized, double-blind, cross-over trial. Twenty patients were evaluable. Both opioids provided adequate analgesia. The variation in plasma morphine concentrations was higher than that of oxycodone, consistent with the lower bioavailability of morphine. Liver dysfunction affected selectively either oxycodone or morphine metabolism. Three patients with markedly aberrant plasma opioid concentrations are presented. Significant individual variation in morphine and oxycodone metabolism may account for abnormal responses during treatment of chronic cancer pain. PMID- 11207002 TI - Pretreatment quality of life of inoperable non-small cell lung cancer patients referred for primary radiotherapy. AB - This study examined the association between the most important prognostic factors in non-small cell lung carcinoma (NSCLC) and self-reported pretreatment quality of life (QoL) and the impact of the presence, severity and changes in respiratory symptoms on general symptoms and QoL. The study included 262 patients. The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and EORTC QLQ-LC13 were used to assess symptoms and QoL before radiotherapy. Patients with inoperable NSCLC showed major differences in self-reported QoL as a function of clinical prognostic factors. A significant association was found between World Health Organization (WHO) performance status and QoL but not other prognostic factors. Dyspnoea was the only respiratory symptom associated significantly with general symptoms, physical and psychosocial functioning and QoL. Furthermore, changes in dyspnoea were associated significantly with changes in physical and role functioning, global QoL and fatigue as assessed 6 weeks after radiotherapy. These results indicate that palliation of dyspnoea may have a significant beneficial effect on QoL and that palliation of other respiratory symptoms is not necessarily associated with improvement of general symptoms, physical and psychological functioning or global QoL. PMID- 11207003 TI - Randomized trial of adjuvant tamoxifen and/or goserelin in premenopausal breast cancer--self-rated physiological effects and symptoms. AB - After primary surgery, 149 premenopausal breast cancer patients, with node negative disease, were randomized to one of four treatment groups: goserelin, tamoxifen, goserelin plus tamoxifen or to a systematically untreated control group. The aim was to assess the effects of adjuvant endocrine therapy in terms of physical symptoms and perception of anxiety and depressive symptoms. Assessments were made before randomization, at 3-4 months and at 12 months. Treatment with goserelin resulted in early and more intense menopausal symptoms, while the effects of tamoxifen were slower and milder. The side effects with goserelin appeared to be alleviated by concurrent tamoxifen except for vasomotor symptoms (hot flashes, sweating, feeling warm). No significant group differences were found for anxiety and depressive symptoms. In conclusion, chemical castration with goserelin was associated with the highest level of physical symptoms. The group treated with tamoxifen alone showed the lowest levels of symptoms among the treatment groups, except for vaginal discharge and irregular bleedings. PMID- 11207004 TI - Is a dense mammographic parenchymal pattern a contraindication to hormonal replacement therapy? AB - The aim of the study was to find out whether the effect of hormonal replacement therapy (HRT) is modified by the mammographic parenchymal patterns on the risk of breast cancer. Subjects were 4163 Finnish women aged 40-47 years at entry who were invited to breast cancer screening every second year from 1982 to 1990. Mammographic parenchymal patterns (Wolfe's classification) were recorded at each screening round. The information, on use of HRT, was recorded from 1984. The follow-up ended in 1993 and up until that time 68 new breast cancers were diagnosed. A Poisson regression model was used in the analysis of the data. Use of HRT was not related to the risk of breast cancer (RR = 0.7, 95% CI 0.4-1.4), whereas mammographic parenchymal pattern was statistically significantly associated with risk of breast cancer. The age-adjusted relative risk of breast cancer among women with P2 versus N1 pattern was 2.5 (95% CI 1.3-4.8) and with DY versus N1 pattern 4.9 (951% CI 1.6-15.1). Women using HRT and with DY pattern were at substantially increased risk of breast cancer (RR = 11.6, 95% CI 2.5 53.6) compared with women not using HRT and with N1 pattern. There was an increased risk of breast cancer among women with DY mammographic parenchymal pattern who used HRT, which was consistent with a synergistic joint effect. PMID- 11207006 TI - Parental cigarette smoking, hard liquor consumption and the risk of childhood brain tumors--a case-control study in northeast China. AB - In this study we examine the effect of parents' lifestyles on the risk of childhood brain tumors. Parents of 82 children newly diagnosed with primary malignant brain tumors and 246 individually matched hospital controls were interviewed in the hospital wards between September 1991 and December 1996. Data were collected on socioeconomic status, parental lifestyle prior to and during the pregnancy, and family history. Odds ratios and 95% confidence intervals were derived through conditional logistic regression. The risk of childhood brain tumors was associated with paternal use of hard liquor prior to the pregnancy: the odds ratios were 3.72 (95% CI = 1.91-7.26) for < or = 15 years of hard liquor consumption and 4.06 (95% CI = 1.09-15.21) for > or = 16 years of hard liquor consumption compared with never consuming hard liquor (test for trend p = 0.0001); the odds ratios increased with increasing lifetime hard liquor consumption. There is little evidence to support an association between childhood brain tumors and parents' smoking prior to or during pregnancy. PMID- 11207007 TI - Squamous cell carcinoma of the oropharynx--an analysis of treatment results in 289 consecutive patients. AB - In this retrospective study the results of primary and salvage treatment of oropharyngeal carcinoma were evaluated. A total of 289 consecutive patients (103 females and 186 males) were included in the study. Most tumours originated in the tonsil area (58%) and comprised stages I 8%, II 19%, III 46% and IV 28%. The primary treatment was delivered with curative intent in 276 cases (96%). Of these, 266 received primary radiotherapy. The median radiation dose was 62 Gy, given as laterally opposed fields to the primary tumour and bilateral neck. Eight patients were treated with primary surgery and two with chemotherapy as part of a curatively intended treatment programme including radiotherapy. Six patients received palliative treatment, and seven were not treated at all. Out of 276 tumours treated with curative intent, 173 reappeared; 72% recurred in T position, 38% in N position, and 12% at distant metastatic sites, some in combination. Salvage surgery was possible in 52 patients, and 24 treatments were successful. Salvage radiotherapy or cryotherapy was used in 22 patients and 4 were controlled. For the entire group, the 5-year locoregional tumour control, disease specific survival and overall survival rates were 38%, 44% and 31%, respectively. For patients treated with curative intent, clinical T- and N-stage, stage, tumour size, gender, age, and pretreatment haemoglobin were significant prognostic parameters in a univariate analysis. The Cox multivariate analysis showed that T stage, N-stage and gender were independent prognostic factors. It is concluded that T-stage, N-stage and gender are significant independent prognostic factors. The primary control of the carcinoma in the T-position is crucial for overall success, but salvage surgery is found to have a favourable success rate in patients suitable for relapse treatment. PMID- 11207005 TI - Serum thyroglobulin as a risk factor for thyroid carcinoma. AB - Samples from a biological serum bank taken up to 23 years prior to diagnosis of thyroid carcinoma were analysed for human thyroglobulin, thyroid-stimulating hormone and thyroxin. After exclusions, the final study material consisted of 59 cases of papillary and follicular carcinomas. These cases were compared with 164 controls, matched for sex, age and time of sample taking. The most interesting finding was that concentrations of thyroglobulin in serum were abnormally elevated in cases compared with controls, equal to or above 30 microg/L, with odds ratio 7.0 (CI 3.1-15.7). This elevation of serum thyroglobulin occurred in 44% of the carcinoma cases. Sensitivity was around 50 for measurements taken up to 15 years prior to diagnosis, but 21 when the interval was over 15 years. Specificity was 89. No differences were found between cases and controls in values for thyroid-stimulating hormone and thyroxin. PMID- 11207008 TI - Comparison between young and old patients with bronchogenic carcinoma. AB - The aim of this study was to compare the clinical characteristics, histological type, stage at diagnosis, treatment and survival of young (< or = 45 years) and older patients with bronchogenic carcinoma. The study was designed as a retrospective review of all lung cancer patients referred to the Kuwait Cancer Control Center over a 10-year period from 1985 to 1994. The study comprised 590 patients with primary bronchogenic carcinoma, of whom 72 (12%) were < or = 45 years of age at the time of diagnosis. Median (range) duration of symptoms, percentage of smokers and male to female ratios for the younger and older patients were 8 (2-48) weeks vs. 8 (1-52) weeks (p = 0.9), 74% vs. 83% (p = 0.06) and 5.5 vs. 5.3, respectively. The majority of patients had advanced stage disease at presentation; 91% of the younger patients had stage III or IV compared with 88% of the older patients (p = 0.1). The histological types for the younger and older patients were 32% vs. 20% for adenocarcinoma (p = 0.01) and 33% vs. 45% for squamous cell carcinoma (p = 0.1). There were more patients in the younger group who had surgery (21% vs. 7.5%) than in the older group (p = 0.001). Follow up data were available for 177 patients out of 190 Kuwaiti national patients (93%). The median (range) survival rates for young and old patients were 8 (3-62) months and 7 (1-174) months, respectively (p = 0.09). Only 6 patients survived for more than 5 years, one (7.6%) from the younger group and 5 (3%) from the older group. Our study shows a relatively high percentage of young patients in our population of lung cancer patients. Apart from the higher incidence of adenocarcinoma in the young group and the fact that these patients had more surgery than the older group, there were no other significant differences between the two groups. PMID- 11207009 TI - Preventing and controlling tuberculosis along the U.S.-Mexico border. AB - Converging factors contribute to elevated tuberculosis (TB) incidence and complicate case management in the U.S. states bordering Mexico. These factors include a) Mexico's higher TB rate; b) low socioeconomic status and limited access to health care in the border area; c) frequent border crossings and travel in the United States for employment, commerce, health services, and leisure; d) language and sociocultural differences; and e) lack of coordinated care across health jurisdictions on both sides of the U.S.-Mexico border. Prevention and control efforts that address the challenges created by border-crossing populations require collaboration among local, state, and national TB control programs in both countries. In June 1999, to facilitate future discussions with Mexican counterparts, CDC convened a meeting of TB control officials from the four U.S. states bordering Mexico (i.e., California, Arizona, New Mexico, and Texas) to address TB prevention and control in the border area. Focus areas included a) surveillance needs, b) case management and therapy completion, c) performance indicators and program evaluation, and d) research needs. Meeting participants' deliberations and resulting proposals for action by CDC and state and local TB control programs are detailed in this report. PMID- 11207010 TI - Elevated level of circulating matrix metalloproteinase-9 in patients with lung cancer. AB - The 72 kDa matrix metalloproteinase (MMP-2) and the 92 kDa matrix metalloproteinase (MMP-9), are type IV collagenases that have been implicated as important factors in cancer invasion and metastasis formation. We have used quantitative zymography and computer-assisted image analysis to measure the levels of MMP-9 and MMP-2 in 19 samples of serum of lung cancer patients and in 23 samples of normal serum. Mean levels of MMP-9 were significantly elevated in cancer samples compared with normal sera (1.33 +/- 0.61 microU microl(-1) vs. 0.37 +/- 0.10 microU microl(-1), P<0.0001). MMP-2 levels did not differ significantly in these two groups. However, there was no significant correlation between serum MMP-9 activity and the disease stage. We found that circulation levels of MMP-9 in lung cancer patients is 3.6-fold higher than in healthy volunteers, however, we do not consider this elevation to be a direct reflection of MMP-9 over-production by tumour cells. PMID- 11207011 TI - Leisure-time energy expenditure in asthmatics and non-asthmatics. AB - An association between obesity and asthma has been documented previously, but the nature of this relationship remains unknown. This study aimed to determine if asthma is associated with a sedentary lifestyle which may explain this association. The energy expenditure (EE) on leisure activities was examined in 16,813 subjects, of at least 12 years of age, who participated in the Canadian National Population Health Survey 1994-95. Energy expenditure was calculated by multiplying the duration of leisure-time physical activity by its estimated metabolic energy cost. Asthma was considered to be present if an affirmative response was given to the question, 'Do you have asthma diagnosed by a health professional?' The average EE (+/- standard error) in males was 2.47 (+/- 0.11) kcal kg(-1) day(-1) for asthmatics and 1.98 (+/- 0.03) kcal kg(-1) day(-1) for non-asthmatics. The corresponding average EEs in females were 1.77 (+/- 0.08) and 1.54 (+/- 0.02) kcal kg(-1) day(-1) for asthmatics and non-asthmatics, respectively. The mean EE values decreased with increasing age. A significant interaction between asthma and age was noted with respect to EE; asthmatics tended to have higher mean EE values than non-asthmatics among younger subjects, and lower mean EE values in older subjects. This effect was more pronounced in females than in males. It was concluded that asthmatics were not consistently inactive compared with non-asthmatics. Leisure-time physical activity cannot explain the positive association between obesity and asthma. PMID- 11207012 TI - Capsaicin cough sensitivity is decreased in smokers. AB - Although capsaicin provocation has been used to evaluate treatment against cough, which is one of the most common respiratory symptoms, there are still methodological considerations that are not fully known. Capsaicin stimulates the unmyelinated slow C-fibres of the sensory nervous system, which leads to coughing. Smoking often leads to respiratory symptoms with cough and phlegm. The aim of this study was to examine the effect of smoking on capsaicin provocation. Subjectively healthy smokers and non-smokers were challenged with capsaicin in increasing doses. The coughs were counted and irritation of the lower airways was graded on a symptom score. Smokers reacted to provocation with significantly fewer coughs, but there was no difference regarding other symptoms. These results are in agreement with the hypothesis that nicotine inhibits or blocks C-fibres of the sensory nervous system of the lower respiratory tract. Clinically, this may serve to explain increasing airway symptoms that are often seen after cessation of smoking. PMID- 11207013 TI - Quality of life in primary care asthma. AB - In primary care, asthma is usually assessed by means of the patients' history regarding symptoms and simple lung-function testing. These outcomes may, however, not be related to other estimates of asthma control such as quality of life. In the present study quality of life was studied in relation to symptoms (visual analogue scale, VAS) and lung function in adult patients with asthma in a primary care setting. In a healthcare centre in Stockholm, 405 individuals diagnosed as having asthma were identified. Out of this number, 120 patients completed the study. Patients were categorized into four groups according to lung function and their response to a question regarding asthma symptoms on the VAS. Quality of life was evaluated with the Asthma Quality of Life Questionnaire (AQLQ) and current treatment was recorded. Quality of life differed significantly between the groups with regard to all domains and overall score; overall score was 6.0 (0.12)--(mean SEM) in group A (VAS < or = 2, normal FEV1), 5.4 (0.24) in group B (VAS < or = 2, low FEV1), 4.8 (0.25) in group C (VAS > 2, normal FEV1) and 4.6 (0.24) in group D (VAS > 2, low FEV1) (P < 0.0001). In general a gradient, with group A having the highest and group D the lowest score, was detected. Experience of symptoms (VAS > 2) was highly related to lower scores in the environmental domain (P < 0.0001). The correlation between FEV1 and quality of life was generally low whereas there was a fairly good correlation between VAS and quality of life (P < 0.0001 for all domains). Patients without steroid treatment had higher quality of life scores than patients treated with steroids. The majority of asthma patients in primary care have high quality of life scores, indicating a low prevalence of symptoms and only slight activity limitations. Evaluation of quality of life enables a more careful grading of asthma status. Furthermore, this measure provides information concerning asthma control that is not revealed by spirometry and simple questions regarding symptoms. PMID- 11207014 TI - Inspiratory muscle training in patients with cystic fibrosis. AB - Little information is available about the effects of inspiratory muscle training in patients with cystic fibrosis (CF). In this study the effects of inspiratory threshold loading in patients with CF on strength and endurance of the inspiratory muscles, pulmonary function, exercise capacity, dyspnoea and fatigue were evaluated. Sixteen patients were assigned to one of two groups using the minimization method: eight patients in the training group and eight patients in the control group. The training was performed using an inspiratory-threshold loading device. Patients were instructed to use the threshold trainer 20 min a day, 5 days a week for 6 weeks. Patients in the training group trained at inspiratory threshold loads up to 40% of maximal static inspiratory pressure (Pimax) and patients in the control group got 'sham' training at a load of 10% of Pimax. No significant differences were found among the two groups in gender, age, weight, height, pulmonary function, exercise capacity, inspiratory-muscle strength and inspiratory-muscle endurance before starting the training programme. Mean (SD) age in the control group was 19 (5.5) years, mean (SD) age in the training group was 17 (5.2) years. Mean FEV1 in both groups was 70% predicted, mean inspiratory-muscle strength in both groups was above 100% predicted. All patients except one, assigned to the training group, completed the programme. After 6 weeks of training, mean inspiratory-muscle endurance (% Pimax) in the control group increased from 50% to 54% (P = 0.197); in the training group mean inspiratory muscle endurance (% Pimax) increased from 49% to 66% (P = 0.003). Statistical analysis showed that the change in inspiratory-muscle endurance (% Pimax) in the training group was significantly higher than in the control group (P = 0.012). After training, in the training group there was a tendency of improvement in Pimax with an increase from 105 to 123% predicted, which just fell short of statistical significance (P = 0.064). After training no significant differences were found in changes from baseline in pulmonary function, exercise capacity, dyspnoea and fatigue. It is concluded that low-intensity inspiratory threshold loading at 40% of Pimax was sufficient to elicit an increased inspiratory-muscle endurance in patients with CF. PMID- 11207015 TI - Psychological disorder in asthma is associated with poor control and poor adherence to inhaled steroids. AB - Previous studies have linked psychological morbidity to poor control of asthma, but have not objectively measured adherence to treatment, and have linked poor adherence to depression, but have not measured asthma severity. This study assessed asthma and psychological morbidity and objectively measured adherence to medication and showed that psychological morbidity in those with asthma is significantly increased when control of asthma is poor, especially when control is poor and adherence to inhaled steroid regimen is low. PMID- 11207016 TI - Respiratory symptoms relate to physiological changes and inflammatory markers reflecting central but not peripheral airways. A study in 60-year-old 'healthy' smokers and never-smokers. AB - The aim of this study was to evaluate the relationship between respiratory symptoms, lung function and inflammatory markers in 'healthy' smokers. The study population was recruited from an epidemiological study with subjects of the same age, 60 years. Only smokers who considered themselves healthy (n=58) and a random sample of never-smokers (n=34) were investigated. All subjects underwent lung function tests--spirometry, carbon monoxide transfer (DLco) and the single-breath N2 method (N2 test)--together with high-resolution computed tomography (HRCT). A flexible bronchoscopy with a bronchoalveolar lavage (BAL) was performed in 30 smokers and 18 never-smokers. Bronchial biopsies were also taken. Smokers who reported non-specific respiratory problems, chronic bronchitis and wheezing in a symptom questionnaire had a lower forced expiratory volume in 1 sec (FEV1), FEV% and specific airway conductance (sGaw), lung function tests supposed to reflect the more central airways, than smokers without respiratory symptoms. A limited number of smokers with occasional non-specific respiratory problems also had more cytotoxic T cells (CD8) in bronchial biopsies. No differences were found in DLCO and the N2 test, lung function tests supposed to reflect the more peripheral airways including the alveoli, HRCT-diagnosed emphysema or inflammatory markers in blood and BAL between smokers with and without respiratory symptoms. It is concluded that even when smokers consider themselves 'healthy' they have mild symptoms that are related more to physiological changes and inflammatory markers that may reflect events in the central airways than to changes that may reflect events in the peripheral airways. PMID- 11207017 TI - Granulocyte markers in induced sputum in patients with respiratory disorders and healthy persons obtained by two sputum-processing methods. AB - Induced sputum is increasingly used to detect and monitor airway inflammation in respiratory diseases. However, the processing of sputum has been rather laborious for clinical practice. The aim of this study was to improve the practicality of induced-sputum studies by simplifying sample processing. Eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), neutrophil lipocalin (HNL) and myeloperoxidase (MPO) were used as biochemical markers of airway inflammation and the results of the study method were compared with a previously validated (reference) method. Induced sputum was obtained from 42 healthy controls, 10 subjects with acute respiratory infection, eight patients with chronic obstructive pulmonary disease (COPD) and 17 asthmatics. The sputum sample was divided into two parts and treated either: (i) by the reference method (released markers), where sputum was homogenized with dithiotreitol and centrifuged to yield cell-free supernatant and a cell pellet, or (ii) by the study method (total markers), where the cells were lysed after homogenization so that cell-associated markers were released and solubilized. For comparison, the four biochemical markers were measured in sputum supernatant and in sputum lysate. The differential cell count was performed from the cell pellet in the reference method. Repeatability was assessed in a group of 16 subjects. The effect of reagents and the recovery of assays were also evaluated. Released and total markers correlated well (ECP r(s)=0.80, P<0.0001; EPO r(s)=0.49, P<0.0001; HNL r(s)=0.87, P<0.0001; MPO r(s)=0.71, P<0.0001). Incubation with dithiotreitol and lysis reagent had no negative influence on marker assays. The within-subject variability of total ECP, MPO and HNL in both methods was small in two measurements taken I week apart. The study method, measuring total inflammatory markers, gave comparable results to the reference method, measuring released markers. In the study method the sputum processing was simplified, which may improve its applicability. PMID- 11207018 TI - Influence of patient posture on oxygen saturation during fibre-optic bronchoscopy. AB - This study was designed to investigate the effect of posture on oxygen saturation during fibre-optic bronchoscopy (FOB). Thirty-eight consecutive patients requiring diagnostic FOB were randomized into two groups according to the initial posture in which the FOB was performed. In group 1 (20 patients), FOB was commenced supine, and in group 2 (18 patients) in a semi-recumbent position (45 degrees from horizontal). Sedation with midazolam was titrated according to clinical response. All patients received atropine 0.6 mg intravenously and topical lignocaine. Observations of peak, trough and plateau oxygen saturation and pulse rate were recorded during six study periods, each lasting 3 min. Periods 1 and 2 were pre- and post-sedation without supplemental oxygen, respectively. The bronchoscope was then inserted into the distal end of the trachea and observations taken during periods 3 and 4 (no supplemental oxygen) and periods 5 and 6 (2 l oxygen by nasal cannulae). In group 1, posture was changed from supine to semi-recumbent from periods 3-4 and reversed in periods 5 and 6. In group 2, posture changes were in reverse sequence. Patients with initial oxygen saturation of less than 90% or showing a fall below 85% during FOB were excluded. Five patients from each group were withdrawn because of hypoxia. In both groups, oxygen saturation fell significantly (P<0.001) following sedation. There was no significant change in saturation (peak, trough or plateau) with change in posture from supine to semi-recumbency (group 1) or the reverse (group 2). These correspond to periods 3-4 and 5 6 in both groups. Supplemental oxygen was associated with a significant rise in oxygen saturation in both postures, attaining levels close to presedation levels. PMID- 11207019 TI - Long-term economic evaluation of intensive patient education during the first treatment year in newly diagnosed adult asthma. AB - The cost-effectiveness of intensive patient education of guided asthma self management given during the first treatment year was evaluated after 5 years of follow-up. Consecutive, newly-diagnosed asthmatics (n = 162, age 18-76 years) were randomized for intensive (80 patients) vs. conventional patient education. Effectiveness was evaluated in terms of lung functions, airway hyperresponsiveness (PD15), and quality of life as measured by the generic 15D and disease-specific St. George's Respiratory Questionnaire (SGRQ). Total treatment costs were also estimated. All patients had anti-inflammatory treatment from the beginning. Sixty-four intervention group (IG) patients and 70 control group (CG) patients were evaluated after 5 years. Forced expiratory volume in 1 sec (FEV1) improved only in the IG, and only during the first treatment year. However, PD15 improved throughout the follow-up. The unscheduled healthcare costs were significantly higher in the CG than in the IG (P = 0.04) and the relative risk for sickness days due to asthma was lower in the IG than in the CG, odds ratio 0.33 (95% CI 0.28; 0.40). However, because there was no significant difference between the groups in any outcome variable or in total costs at 5 years, the incremental cost-effectiveness ratio could not be calculated. The first year intervention had only a short-term beneficial treatment effect, which the CG could catch up during the two last follow-up years, except in FEV1. The peak expiratory flow (PEF)-based self-management had no advantage over the symptom-based self-management. However, the intervention had a consistent tendency of being less costly in the long-run. It is possible to conclude tentatively that regular effective medical treatment and control visits during the first treatment year is at least as important for the long-term treatment result as intensive patient education. PMID- 11207020 TI - Comparison between formoterol 12 microg b.i.d. and on-demand salbutamol in moderate persistent asthma. AB - Inhalation of on-demand salbutamol (ODS) several times daily is sometimes the only beta2-agonist prescribed in moderate persistent asthma, whereas a long acting beta2-agonist should be added. This trial aimed to compare the efficacy of formoterol dry-powder capsule 12 microg b.i.d. (Foradil) and ODS in patients with moderate persistent asthma treated with inhaled corticosteroids, in the conditions of real practice. Two hundred and fifty-nine patients were randomized (formoterol; 130; ODS: 129) in this open, parallel-group trial. The mean increases in morning peak expiratory flow (PEF primary variable) and evening PEF over the 3-month treatment period were statistically significantly higher with formoterol: +25.7 and +24.1 l min(-1), respectively vs. +4.5 and +0.5 l min(-1) respectively with ODS. The increase in FEV1 was statistically significantly higher with formoterol at months 1 and 3. Formoterol reduced the use of salbutamol as rescue medication by two-thirds. The percentages of symptom-free days and nights statistically significantly increased with formoterol (+20% and +33% respectively), but did not significantly change with ODS. Clinically relevant and statistically significant improvement in the mean total score of the St George's Hospital Respiratory Questionnaire was observed in the formoterol group. Adverse events were similar in the two groups. The results show that treatment with formoterol has significant advantages over ODS in patients with moderate persistent asthma. PMID- 11207021 TI - A comparison of three disease-specific and two generic health-status measures to evaluate the outcome of pulmonary rehabilitation in COPD. AB - The use of health status as an outcome measure is becoming more widespread in pulmonary rehabilitation. There are a number of health status measures but the choice remains uncertain. Three disease specific measures and two generic measures of health status were employed to observe their relative sensitivity to a 7-week course of pulmonary rehabilitation. Patients with stable chronic obstructive pulmonary disease (COPD) were recruited into a rehabilitation programme. They completed a shuttle-walking test and three disease-specific questionnaires: the Chronic Respiratory Questionnaire (CRQ), the St. George's Hospital Respiratory Questionnaire (SGRQ) and the Breathing Problems Questionnaire (BPQ). Patients also completed two generic questionnaires: a global quality-of-life scale and an activity checklist. Ninety-seven patients [58 male mean (SD) age 67 (8.7) years] completed the course over a 12-month period. The mean pre-rehabilitation (SD) FEV1 was 1.06 (0.59) l. The shuttle-walking test and the treadmill-endurance test increased significantly after rehabilitation (P<0.001). All three disease-specific questionnaires improved significantly (the CRQ and SGRQ improved beyond minimum clinically important difference). The global score improved significantly whilst the 'things people do' decreased. All three disease-specific measures were responsive to pulmonary rehabilitation. However the operator-led CRQ appears to be the most sensitive short-term outcome measure. PMID- 11207022 TI - The influence of the severity of community-acquired pneumonia on the usefulness of blood cultures. AB - The value of blood cultures in community-acquired pneumonia (CAP) has been questioned. At issue is the potential for blood cultures to change management. We prospectively studied the yield and impact of blood cultures in patients admitted with CAP. Two hundred and nine subjects had at least two blood cultures prior to receiving antibiotics. The severity of CAP was graded using the Pneumonia Severity Index (PSI). Twenty-nine patients (13.9%) had a pathogen identified by blood culture. The yield of blood cultures increased with PSI grade (I--5.3%, II- 10.2%, III--10.3%, IV--16.1%, V--26.7%), as did the likelihood of blood cultures changing antibiotic therapy (I to III--0%, IV--9.7%, V--20.0%). One hundred and seventy-nine (85.6%) patients received a quinolone, limiting the impact of pathogens resistant to beta-lactams. Four of 16 patients (25.0%) with a culture (blood or sputum)-guided change in antibiotic therapy died, compared to five of 31 patients (16.1%) who had an empiric change. Blood cultures are of minimal value in mild to moderate CAP, and should be limited to patients with PSI grade IV or V CAP unless a specific risk factor for pathogens resistant to the empiric therapy is present. PMID- 11207023 TI - Changes in asthma drug therapy costs for patients receiving chronic montelukast therapy in the U.K. AB - The aim of this study was to assess changes in the costs of asthma drug therapy before and during the use of chronic montelukast treatment in the U.K. A retrospective cohort analysis of a primary care database in the U.K. was carried out. Patients with chronic montelukast use (> or = 140 once-daily doses) were selected for analysis. Benchmarking data were obtained for matched patients with chronic inhaled corticosteroid (ICS) use and patients with chronic salmeterol therapy with concomitant ICS use. The main outcome measures were changes in utilization and monthly cost of asthma therapies costs. Asthma patients experienced significant (P<0.05) reductions in the monthly costs of ICS, short acting beta-agonists and antibiotics following chronic montelukast therapy. Monthly concomitant drug costs were reduced by Pound Sterling 7.49 per month, which offset 27.5% of the additional cost of montelukast, yielding an increase in total drug costs of Pound Sterling 19.78 per month. Meanwhile, increased total drug costs for matched patients with chronic ICS use, and matched patients with chronic salmeterol therapy and concomitant ICS use, increased by Pound Sterling 5.37 per month and Pound Sterling 44.55 per month respectively. Additionally, patients using chronic montelukast therapy experienced a statistically significant (P<0.05) reduction in the use of short acting beta-agonists, and antibiotics, suggesting improvement in asthma control. Chronic use of montelukast therapy is associated with a reduction of concomitant drug therapy costs. PMID- 11207024 TI - The natural history of respiratory allergy: a follow-up study of 99 patients up to 10 years. AB - A strict relationship between allergic rhinitis and allergic asthma has been seen recently, and in many ways respiratory allergy could be seen as a single disorder of the airways. The link between rhinitis and asthma can be elucidated only by studying the natural history of the disease over long periods. We describe the follow-up of 99 allergic patients up to 10 years and the evolution of their disease. Ninety-nine patients (50 male, 49 female, mean age 31 years) out of 142, suffering from allergic rhinitis or allergic asthma, could be monitored up to 10 years after the initial diagnosis. Demographics, sensitizations and smoke habit were assumed as evaluation parameters. At baseline, 44 patients suffered from AR alone, 12 from AA alone and 43 from AR+AA. After 10 years, 31.8% of the AR patients developed developed AA and 50% of the patients with AA developed AR. Only the familial history for atopy significantly influenced the disease's evolution, whereas gender, age, smoking habit and skin sensitization did not. Sixty-five percent of patients with a single sensitization at the beginning developed new sensitizations. In conclusion, this long-term survey confirms that a relevant percentage of patients with AR alone or AA alone have a progression of the disease. PMID- 11207025 TI - What time of day do patients take steroid tablets? PMID- 11207026 TI - Organization of the CYP1A cluster on human chromosome 15: implications for gene regulation. AB - The sequence and organization of the CYP1A cluster on human chromosome 15 was determined. A human genomic clone from a BAC library, containing both CYP1A1 and CYP1A2 genes, was isolated and sequenced. The results of Southern blot analysis using human genomic DNA were compatible with the structure of the BAC clone. The CYP1A1 and CYP1A2 genes are separated by a 23 kb segment that contains no other open reading frames. The CYP1A1 and CYP1A2 genes are in opposite orientation, revealing that the 5' flanking region is in common between the two genes. Analysis of the sequence obtained revealed the presence of xenobiotic response elements (XREs) previously reported for CYP1A1 and CYP1A2 and several additional consensus sequences for putative XREs. The presence of all the XREs upstream of both genes suggest that some of the regulatory elements known to control CYP1A1 gene expression, could also control CYP1A2 gene expression. PMID- 11207027 TI - Serotonin receptor gene HTR3A variants in schizophrenic and bipolar affective patients. AB - Serotonin receptor genes have always been considered excellent candidate genes in the aetiology of neurogenetic diseases. In this study, we assessed sequence variations of the HTR3A gene. For this purpose, we established exon-specific primers and analysed DNA samples from 165 unrelated individuals including 70 schizophrenic patients, 48 patients with bipolar affective disorder and 47 healthy control persons using polymerase chain reaction/single-strand conformational polymorphism analysis. We discovered six sequence variants, five of which represent polymorphisms. These polymorphisms could not be associated with schizophrenia and bipolar affective disorder (P = 0.055-1). We also detected a missense mutation in exon 9 in a schizophrenic patient at a conserved position (Pro391Arg). To determine the incidence of this substitution an extended set of 358 schizophrenic patients and 155 control individuals was investigated. The Pro391Arg mutation was not detected in these schizophrenic patients and controls screened. However, a second missense mutation (Arg344His) was detected in one schizophrenic patient, but not in any of the controls. These results suggest that the observed mutations in HTR3A are rare and therefore do not play a major role in the aetiology of the disorder. Further studies are needed to support the hypothesis that HTR3A may contribute to the schizophrenia in these patients. PMID- 11207028 TI - Inhibition of cytochrome P450 2C9 activity in vitro by 5-hydroxytryptamine and adrenaline. AB - In the present study, the occurrence of a modulatory effect of 14 neurotransmitters, precursors and metabolites on the cytochrome P450 2C9 (CYP2C9) enzyme activity, as determined by diclofenac 4-hydroxylation, was studied in human liver microsomes. Two indoleamines, 5-hydroxytryptamine (5-HT) and adrenaline, showed a non-competitive-type inhibitory effect of approximately 90% of the diclofenac 4-hydroxylase activity, with Ki values of 63.5 (0.7 and 156 (89.3 microM, respectively. The rest of substances analysed were weak inhibitors or had no inhibitory effect. CYP2C subfamily is present in human brain, although CYP2C9 isozyme has not yet been identified in this tissue, and CYP2C9 is involved in the metabolism of psychoactive drugs. Therefore, the fact that endogenous compounds could modulate the CYP2C9 activity, suggests that an hypothetical local activity of brain CYP2C9 might be susceptible to regulatory mechanisms. The possible clinical implications of this modulation are discussed. PMID- 11207029 TI - Genetic polymorphisms of cytochrome P450 2A6 in a case-control study on lung cancer in a French population. AB - Cytochrome P450 2A6 (CYP2A6) is involved in the C-oxidation of nicotine and in the metabolic activation of tobacco nitrosamines. Recent data have suggested that CYP2A6 genetic polymorphisms might play a role in tobacco dependence and consumption as well as in lung cancer risk. However, the previously published studies were based on a genotyping method that overestimated the frequencies of deficient alleles, leading to misclassification for the CYP2A6 genotype. In this study, we genotyped DNA from 244 lung cancer patients and from 250 control subjects for CYP2A6 (wild-type allele CYP2A6*1, and two deficient alleles: CYP2A6*2, and CYP2A6*4, the latter corresponding to a deletion of the gene) using a more specific procedure. In this Caucasian population, we found neither a relation between genetically impaired nicotine metabolism and cigarette consumption, nor any modification of lung cancer risk related to the presence of defective CYP2A6 alleles (odds ratio = 1.1, 95% confidence interval = 0.7-1.9). PMID- 11207030 TI - Polymorphisms in CYP2D6 duplication-negative individuals with the ultrarapid metabolizer phenotype: a role for the CYP2D6*35 allele in ultrarapid metabolism? AB - Ultrarapid drug metabolism mediated by CYP2D6 is associated with inheritance of alleles with duplicated or amplified functional CYP2D6 genes. However, genotyping for duplicated CYP2D6 alleles only explains a fraction (10-30%) of the ultrarapid metabolizer phenotypes observed in Caucasian populations. Using a sample of CYP2D6 duplication-negative ultrarapid metabolizer subjects and selected control subjects with extensive metabolism, we examined parts of the CYP2D7 pseudogene, and the promoter region and 5'-coding sequence of CYP2D6 for polymorphisms possibly associated with the ultrarapid metabolizer phenotype. In an initial screening of 17 subjects (13 ultrarapid metabolizers and four extensive metabolizers), we identified three DNA variants in the 5'-end of the CYP2D7 pseudogene and 29 variants in the 5'-end of the CYP2D6 gene. Five variants were then selected for examination in a larger sample of subjects having the ultrarapid metabolizer (n = 27) or extensive metabolizer phenotype (n = 77). Subsequent statistical analyses of allele, genotype and estimated haplotype distributions showed that the 31A allele of the 31G > A (Val(II)Met) polymorphism was significantly more frequent in ultrarapid metabolizer subjects than in extensive metabolizer subjects (P = 0.04). Also, estimation of haplotype frequencies suggested that one of the haplotypes with the 31A variant was significantly more frequent among the ultrarapid metabolizers compared with the extensive metabolizers (P = 0.03). The average metabolic ratio was significantly lower in subjects possessing the 31A allele compared with subjects homozygous for the 31G allele (P = 0.02). We also observed a nonsignificant over-representation of the G-allele of a - 1584 C > G promoter polymorphism in the ultrarapid metabolizer group. Since our results are based on a relatively low number of subjects, further studies on larger samples and functional analyses of the polymorphisms detected are necessary to determine the role of the 31G > A and - 1584C > 6 variants in CYP2D6 duplication-negative ultrarapid metabolizer subjects. PMID- 11207031 TI - Sulfation pharmacogenetics: SULT1A1 and SULT1A2 allele frequencies in Caucasian, Chinese and African-American subjects. AB - Sulfotransferase (SULT) enzymes catalyze the sulfate conjugation of drugs, other xenobiotics, neurotransmitters and hormones. The genes for SULT1A1 and SULT1A2 contain common genetic polymorphisms that are associated with individual variations in levels of enzyme activity as well as variations in biochemical and physical properties. We set out to compare the frequencies of common SULT1A1 and SULT1A2 alleles in Caucasian, Chinese and African-American subjects. Allele frequencies for SULT1A1*1, *2 and *3 in 242 Caucasian subjects were 0.656, 0.332 and 0.012, respectively. Frequencies of those same alleles were significantly different in 290 Chinese subjects: 0.914, 0.080 and 0.006, respectively, as were frequencies in 70 African-American subjects: 0.477, 0.294 and 0.229, respectively. Ethnic variation in allele frequencies was also observed for SULT1A2, with frequencies in Caucasian subjects for SULT1A2*1, *2 and *3 of 0.507, 0.389 and 0.104; frequencies in Chinese of 0.924 and 0.076 with no *3 alleles observed; and, finally, in African-Americans frequencies of 0.637, 0.249 and 0.114, respectively. We also found that SULT1A1*2 and SULT1A2*2, the most common variant alleles for these two genes, were in positive linkage disequilibrium in all three populations studied, with D' values of 0.776 in Caucasian (P < 0.001), 0.915 in Chinese (P < 0.001) and 0.864 in African-American subjects (P < 0.001). These observations represent a step towards determining the possible functional implications for individual variations in sulfate conjugation of common genetic polymorphisms for SULT1A1 and SULT1A2. PMID- 11207032 TI - Allele and genotype frequencies of polymorphic cytochromes P4502D6, 2C19 and 2E1 in aborigines from western Australia. AB - The polymorphisms of the important xenobiotic metabolizing enzymes CYP2D6, CYP2C19 and CYP2E1 have been studied extensively in a large number of populations and show significant heterogeneity in the frequency of different alleles/genotypes and in the prevalence of the extensive and poor metabolizer phenotypes. Understanding of inter-ethnic differences in genotypes is important in prediction of either beneficial or adverse effects from therapeutic agents and other xenobiotics. Since no data were available for Australian Aborigines, we investigated the frequencies of alleles and genotypes for CYP2D6, CYP2C19 and CYP2E1 in a population living in the far north of Western Australia. Because of its geographical isolation, this population can serve as a model to study the impact of evolutionary forces on the distribution of different alleles for xenobiotic metabolizing enzymes. Twelve CYP2D6 alleles were analysed. The wild type allele *1 was the most frequent (85.81%) and the non-functional alleles (*4, * 5, * 16) had an overall frequency of less than 10%. Only one subject (0.4%) was a poor metabolizer for CYP2D6 because of the genotype *5/*5. For CYP2C19, the frequencies of the *1 (wild-type) and the non-functional (*2 and *3) alleles were 50.2%, 35.5% and 14.3%, respectively. The combined CYP2C19 genotypes (*2/*2, *2/*3 or *3/*3) correspond to a predicted frequency of 25.6% for the CYP2C19 poor metabolizer phenotype. For CYP2EI, only one subject had the rare c2 allele giving an overall allele frequency of 0.2%. For CYP2D6 and CYP2C19, allele frequencies and predicted phenotypes differed significantly from those for Caucasians but were similar to those for Orientals indicating a close relationship to East Asian populations. Differences between Aborigines and Orientals in allele frequencies for CYP2D6* 10 and CYP2E1 c2 may have arisen through natural selection, or genetic drift, respectively. PMID- 11207033 TI - Variation in enzymes of arylamine procarcinogen biotransformation among bladder cancer patients and control subjects. AB - Arylamines such as 2-naphthylamine and 4-aminobiphenyl are suspected human bladder procarcinogens that require bioactivation to DNA-reactive species to exert their carcinogenic potential. The goals of the present study were (i) to assay for the presence of the arylamine acetyltransferases NAT1 and NAT2, and of the cytochrome P450 isoform CYP1A2, in human bladder epithelium; and (ii) to determine whether the activities of these arylamine biotransforming enzymes differ between bladder cancer patients and control subjects. We measured in-vitro enzyme activities in biopsies of normal, undiseased bladder epithelium obtained from 103 bladder cancer patients. NAT1 activity was detectable in all samples, with mean levels higher than those found in human liver. Kinetic evidence also suggested low levels of NAT2 expression in this tissue, but there was no detectable CYP1A2 by either enzymatic or immunochemical measurements. We also compared several probe drug indices of in-vivo NAT1, NAT2 and CYP1A2 activity between 53 bladder cancer patients and 96 cancer-free control subjects who were carefully matched for age, gender and smoking status. NAT1 and NAT2 genotypes were also determined. No significant differences were found between bladder cancer patients and control subjects for a number of individual phenotypic or genotypic predictors of enzyme function. Our results suggest that although expression of particular arylamine biotransforming enzymes within the bladder tissue could play a significant role in locally bioactivating arylamine procarcinogens in theory, interindividual variations in CYP1A2, NAT1 and NAT2 activities do not significantly differ between bladder cancer patients and control subjects when potential arylamine exposures are controlled for PMID- 11207034 TI - Polymorphisms in the human paraoxonase (PON1) promoter. AB - Paraoxonase (PON1) is a protein component of high-density lipoprotein (HDL) particles that protects against oxidative damage to both low-density lipoprotein and HDL and detoxifies organophosphorus pesticides and nerve agents. A wide range of expression levels of PON1 among individuals has been observed. We examined the promoter region of PON1 for genetic factors that might affect PON1 activity levels. We conducted a deletion analysis of the PON1 promoter region in transient transfection assays and found that cell-type specific promoter elements for liver and kidney are present in the first 200bp upstream of the coding sequence. Sequence analysis of DNA from a BAC clone and a YAC clone identified five polymorphisms in the first 1000 bases upstream of the coding region at positions 108, -126, -162, -832 and -909. Additionally, the promoter sequences of two individuals expressing high levels of PON1 and two individuals expressing low levels of PON1 were analysed. The two polymorphisms at -126 and -832 had no apparent effect on expression level in the reporter gene assay. The polymorphisms at position -909, -162 (a potential NF-I transcription factor binding site) and 108 (a potential SP1 binding site) each have approximately a two-fold effect on expression level. The expression level effects of the three polymorphisms appear not to be strictly additive and may depend on context effects. PMID- 11207035 TI - Ethnic variability in the allelic distribution of human aryl hydrocarbon receptor codon 554 and assessment of variant receptor function in vitro. AB - The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcriptional regulator of several genes including the cytochrome P4501 (CYP1) family as well as genes encoding factors involved in cell growth and differentiation. In mice, several polymorphic forms of the AHR are known, some of which have altered affinity for toxic and carcinogenic ligands. Remarkably little genetic variation has been detected in the human AHR gene. In studies on human AHR, Kawajiri et al. (Pharmacogenetics 1995; 5:151-158) reported a variation at codon 554 that results in an amino acid change from arginine to lysine; the frequency of the variant allele in a Japanese population (n = 277) was 0.43. We investigated the Lys554 allele in 386 individuals of various ethnic origins and found the frequency to be: 0.58 in Ivory Coast Africans (n = 58); 0.53 in a mixed African group (n = 20); 0.39 in Caribbean-Africans (n = 55); 0.32 in Canadian Chinese (n = 41); 0.14 in North American Indians (n = 47); 0.12 in French Canadian Caucasians (n = 20); 0.11 in a mixed ethnicity North American group (n = 45); 0.09 in Canadian Inuits (n = 22); and 0.07 in German Caucasians (n = 78). We expressed the human Lys554 allele in an in-vitro transcription-translation system and found that the receptor bearing the R554L substitution had an equivalent ability to that of the wild-type receptor to bind to a dioxin-responsive element following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The Lys554 allele also was equivalent to the wild-type receptor at stimulating CYP1A1 mRNA expression when transfected into TCDD-treated receptor-deficient mouse Hepa-1 cells. It is not yet known if any of the wide variations in allele frequency at codon 554 are related to ethnic differences in susceptibility to adverse effects of environmental chemicals. PMID- 11207036 TI - The prognostic advantage of preoperative intratumoral injection of OK-432 for gastric cancer patients. AB - To investigate, by a multi-institutional randomized trial, the prognostic significance of the augmentation of tumour-infiltrating lymphocytes (TILs) by preoperative intratumoral injection of OK-432 (OK-432 it), a bacterial biological response modifier, in patients with gastric cancer. The 10-year survival and disease-free survival were examined and analysis of the factors showing survival benefit was performed. 370 patients who had undergone curative resection of gastric cancer were enrolled in this study and followed up for 10 years postoperatively. Patients were randomized into either an OK-432 it group or a control group. Ten Klinishe Einheit (KE) of OK-432 was endoscopically injected at 1 to 2 weeks before the operation in the OK-432 it group. Both groups received the same adjuvant chemoimmunotherapy consisting of a bolus injection of mitomycin C (0.4 mg kg(-1) i.v.) and administration of tegafur and OK-432 from postoperative day 14 up to 1 year later. Tegafur (600 mg day(-1)) was given orally and OK-432 (5 KE/2 weeks) was injected intradermally for a maintenance therapy. The TILs grades in resected tumour specimens and presence of metastasis and metastatic pattern in dissected lymph nodes were examined. Multivariate analysis was performed to determine the efficacy of OK-432 it on prognostic factors. All patients were followed up for 10 years. The overall 5- and 10-year survival rates and disease-free survival rates of the OK-432 it group were not significantly higher than those of the control group. However, OK-432 it significantly increased the 5- and 10-year survival rates of patients with stage IIIA + IIIB, moderate lymph node metastasis (pN2), and positive TILs. OK-432 it was most effective at prolonging the survival of patients who had both positive TILs and lymph node metastasis. The OK-432 it group with positive TILs showed a significant decrease in metastatic lymph node frequency and in the number of lymph node micro- metastatic foci when compared to the control group. This study showed that only one time preoperative OK-432 it, particularly when it triggers TILs, is effective for reduction of regional lymph node metastasis. OK-432 it probably acts partly by eliminating micro-metastatic foci in lymph nodes. Preoperative intratumoral injection of OK-432 is technically very easy and has no serious adverse effects, so it is a promising form of neoadjuvant immunotherapy for advanced gastric cancer. PMID- 11207037 TI - Estimation of glomerular filtration rate in cancer patients. AB - The frequent need to obtain an estimate of renal function in cancer patients, not least for targeting carboplatin dose, has led to a number of approaches to estimate glomerular filtration rate (GFR). This study aimed to develop a simple and reliable method to estimate GFR using readily-available patient characteristics. Data from 62 patients with estimates of 51Cr-EDTA clearance were analysed to determine the most appropriate formula relating this method of measuring GFR to patient characteristics. The population pharmacokinetics of 51Cr EDTA were analysed using NONMEM to evaluate the influence of each covariate. The formulae derived were then validated using a further 38 patients and compared with those obtained using existing formulae. 51Cr-EDTA clearance (GFR) was positively related to Dubois surface area, negatively related to age, and inversely related to serum creatinine (SCr). Females had lower 51Cr-EDTA clearance than males. The enzymatic method of SCr assay gave more reliable results than the Jaffe colorimetric method. A measure of creatine kinase significantly improved the estimation of GFR. The new formula produced estimates of GFR which were less biased (Mean Prediction Error = -3%) and more precise (Mean Absolute Prediction Error = 12%) than Cockcroft and Gault (-8% and 16%) or Jelliffe (-15% and 19%) estimates. The formulae developed here can be used to provide reliable estimates of GFR, particularly in regard to targeted dosing of carboplatin. PMID- 11207038 TI - Treatment of advanced neuroblastoma: feasibility and therapeutic potential of a novel approach combining 131-I-MIBG and multiple drug chemotherapy. AB - Biological and clinical observations suggest that initial marked reduction of resistant clones may be critical in any attempt to improve long-term results in advanced neuroblastoma (NB). The aim of this pilot study is to determine short term toxicity and efficacy of a new therapeutic model based on the simultaneous use of multiple drug chemotherapy and specific irradiation using 131-I-MIBG. The study population consisted of 21 patients, from 1 to 8 years of age with good 131 I-MIBG uptake. 16 extensively pre-treated patients with refractory or relapsed disease were divided into 2 groups. In Group 1 (9 patients) the basic chemotherapy regimen consisted in cisplatin at the dose of 20 mg/m(2) i.v. per day infused over 2 h, for 4 consecutive days; on day 4 Cy 2 g/m(2) i.v. was administered over 2 h followed by Mesna. Group 2 (7 patients) was treated with basic chemotherapeutic regimen plus VP16 and Vincristine. VP16 at the dose of 50 mg/m(2) i.v. per day was administered as a 24 h infusion on days 1-3; Vincristine 1.5 mg/m(2) i.v. was administered on days 1 and 6. On day 10 a single dose of 131 I-MIBG (200 mCi) with a high specific activity (>1.1 GBq/mg) was administered to both Groups by i.v. infusion over 4-6 hours. A further 5 patients were treated at diagnosis: 2 with the same regimen as Group 1 and 3 with the same as Group 2. The severity of toxicity was graded according to World Health Organization (WHO) criteria. Assessment of tumour response was monitored 4-6 weeks after the beginning of combined therapy (CO-TH). Response was defined according to INSS (International Neuroblastoma Staging System) criteria. No extra-medullary toxicity was observed in any patient. Haematological toxicity was the only toxicity observed and seemed mainly related to chemotherapy. Myelosuppression was mild in the 5 patients treated at diagnosis. No serious infections or significant bleeding problems were observed. In the 16 resistant patients, 12 PR, 1 mixed response and 3 SD were obtained. In the 5 patients treated at diagnosis 2 PR, 1 CR and 2 VGPR were observed. No alteration in 131-I-MIBG uptake was observed after the chemotherapy preceding radio-metabolic treatment. The therapeutic results of this pilot regimen of CO-TH resulted in a high percentage of major response after only a single course in both resistant patients and patients treated at diagnosis. Because of the minimal toxicity observed in patients studied at diagnosis so far, there is room for gradual intensification of the treatment. It is to be hoped that this suggested novel approach may represent an important route of investigation to improve final outcome in patients with advanced NB. PMID- 11207039 TI - A phase II study of sequential chemotherapy with docetaxel after the weekly PELF regimen in advanced gastric cancer. A report from the Italian group for the study of digestive tract cancer. AB - In advanced gastric cancer, we investigated feasibility and activity of sequential chemotherapy with docetaxel after an intensive weekly regimen consisting of cisplatin, epidoxorubicin, fluorouracil, leucovorin (PELF) plus filgrastim. Chemotherapy-naive patients with relapsed or metastatic gastric cancer received 8 weekly administrations of chemotherapy with cisplatin 40 mg/m(2), fluorouracil 500 mg/m(2), epidoxorubicin 35 mg/m(2), 6S-stereoisomer of leucovorin 250 mg/m(2) and glutathione 1.5 g/m(2). On the other days filgrastim 5 microg kg(-1) was administered by subcutaneous injection. Subsequently, patients with partial response or stable disease received 3 cycles of docetaxel 100 mg/m(2) every 3 weeks. 40 patients have been enrolled and they are evaluable for response and toxicity. After the PELF regimen, 3 patients achieved complete response, 13 patients showed partial response, 21 patients had stable disease and 3 patients progressed (40% response rate; 95% CI 25% to 55%). After docetaxel, 9 out 34 patients improved the outcome (26.5%); 7 patients with stable disease achieved partial response and 2 patients with partial response achieved complete response. The overall response rate in the 40 patients was 57.5% (95% CI, 42.5% to 72.5%). The PELF regimen did not cause any grade IV toxicity, the most frequent grade III acute side-effects were thrombocytopenia and vomiting which occurred in the 10% of 320 PELF cycles. Docetaxel caused grade III-IV neutropenia and thrombocytopenia in the 10% and the 19% of cycles respectively. Fatigue was a frequent side-effect during both PELF and docetaxel chemotherapy. The sequential application of docetaxel after PELF chemotherapy gained major objective responses with manageable toxicity. This strategy is worth of further investigation in the setting of palliative or neoadjuvant chemotherapy. PMID- 11207040 TI - The frequency of the predominant Jewish mutations in BRCA1 and BRCA2 in unselected Ashkenazi colorectal cancer patients. AB - It is presently unclear whether carriers of BRCA1 mutations have an increased risk for colorectal cancer (CRC). To gain insight into this issue, 225 unselected Ashkenazi Jewish CRC patients were tested for the presence of the three common Jewish BRCA1/2 germline mutations: 185delAG and 5382insC (BRCA1) and 6174delT (BRCA2). A total of four carriers was found (4/225, 1.78%). This frequency is similar to the estimated normal Ashkenazi population frequency, thus suggesting that these specific mutations do not contribute to CRC predisposition. PMID- 11207041 TI - The rate of the 6174delT founder Jewish mutation in BRCA2 in patients with non colonic gastrointestinal tract tumours in Israel. AB - Inherited predisposition occurs in 5-10% of all gastrointestinal (GI) cancer patients, but with the exception of colorectal cancer (CRC), the genes involved in conferring genetic susceptibility remain largely unknown. Indirect evidence indicates that germline mutations in BRCA2 might be associated with an increased risk for various GI malignancies. A single mutation (6174delT) occurs in the BRCA2 gene in high-risk breast ovarian cancer families of Jewish Ashkenazi origin, in about 1% of the general Ashkenazi population, and rarely in non Ashkenazi Jews. In order to assess the contribution of this germline mutation to non-CRC GI cancer in Jewish Israeli patients, we tested 70 unselected, consecutive Jewish Ashkenazi patients with gastrointestinal malignancies for this mutation by PCR amplification and modified restriction enzyme digests. Patients' age range was 38-90 years (mean 65.8+/-11.8 years). The most common malignancies were gastric cancer (n = 35) and exocrine pancreatic cancer (n = 23). Overall, 6 mutation carriers were detected: 3/23 (13%) of the patients with pancreatic cancer, 2/35 (5.7%) of patients with gastric cancer and 1/4 (25%) of patients with bile duct cancer. The 8.6% mutation carrier rate among patients is a rate significantly higher than that of the general Ashkenazi population (1.16%, P = 0.0002). We conclude that the rate of the predominant Jewish BRCA2 mutation in patients with gastric and pancreatic cancer significantly differ from that of the general population of the same ethnic origin. Thus, BRCA2 mutations probably contribute to gastrointestinal tumorigenesis other then colon cancer, and the surveillance scheme for mutation carriers should incorporate this information. PMID- 11207042 TI - Screening of male breast cancer and of breast-ovarian cancer families for BRCA2 mutations using large bifluorescent amplicons. AB - 41 breast cancer or breast-ovarian cancer families, including 12 families with at least one affected first-degree male relative, were screened for mutations in the BRCA2 gene. Mutations had not been found in the BRCA1 gene of these families. Chemical cleavage of mismatch was used to identify nucleotide changes within large PCR products (average size 1.2 kb) that carried strand-specific fluorescent end-labels. 15 amplicons were sufficient to scan 18 exons, including the large exon 11. The remaining 9 small exons were examined by Denaturing Gradient Gel Electrophoresis. The high sensitivity of this approach was documented by the detection, in these 41 patients, of all 9 exonic single nucleotide polymorphisms reported with heterozygosity >0.1. Truncating BRCA2 mutations were found in 7 of the 41 families. 3 of them were in the group of 12 families comprising cases of male breast cancer. Since the methods used here have no bias for particular types of mutations, these data confirm the high proportion of frameshifts among mutations in BRCA2. However, relevant single nucleotide substitutions were also found: one resulting in a stop codon and another one, present in a male patient, was the previously reported change Asp2723His, that affects a highly conserved region of the BRCA2 protein. This study indicates a BRCA2 contribution of 10% (95% CI 2.5-17.5) to our original cohort of 59 breast-ovarian cancer families, whereas the contribution of BRCA1 had been estimated at 46% (95% CI 33-59). PMID- 11207043 TI - A role for chromosomal instability in the development of and selection for radioresistant cell variants. AB - Chromosome instability is a common occurrence in tumour cells. We examined the hypothesis that the elevated rate of mutation formation in unstable cells can lead to the development of clones of cells that are resistant to the cancer therapy. To test this hypothesis, we compared chromosome instability to radiation sensitivity in 30 independently isolated clones of GM10115 human-hamster hybrid cells. There was a broader distribution of radiosensitivity and a higher mean SF(2)in chromosomally unstable clones. Cytogenetic and DNA double-strand break rejoining assays suggest that sensitivity was a function of DNA repair efficiency. In the unstable population, the more radioresistant clones also had significantly lower plating efficiencies. These observations suggest that chromosome instability in GM10115 cells can lead to the development of cell variants that are more resistant to radiation. In addition, these results suggest that the process of chromosome breakage and recombination that accompanies chromosome instability might provide some selective pressure for more radioresistant variants. PMID- 11207044 TI - High rates of loss of heterozygosity on chromosome 19p13 in human breast cancer. AB - We have recently discovered that the nuclear matrix protein SAFB is an oestrogen receptor corepressor. Since it has become clear that many steroid receptor cofactors play important roles in breast tumorigenesis, we investigated whether SAFB could also be involved in breast cancer. To address this question, the gene locus was examined for structural alterations in breast cancer tissue. Laser capture microdissection was used for isolating DNA from paired primary breast tumour and normal tissue specimens, and the loss of heterozygosity (LOH) at chromosome 19p13.2-3 was determined by use of microsatellite markers. LOH was detected at the marker D19S216, which colocalizes with the SAFB locus, in specimens from 29 (78.4%) of 37 informative patients. The peak LOH rate occurred at D19S216 near the SAFB locus, with LOH frequencies ranging from 21.6% to 47.2% at other markers. The finding of a very high LOH rate at the marker D19S216 strongly indicates the presence of a breast tumour-suppressor gene locus. While preliminary findings of mutations in SAFB suggest that this indeed may be a promising candidate, other potential candidate genes are located at this locus. PMID- 11207045 TI - Copy number gain at 12q12-14 may be important in the transformation from follicular lymphoma to diffuse large B cell lymphoma. AB - The purpose of this study was to identify novel areas of genomic copy number change associated with transformation from follicular lymphoma (FL) to diffuse large B cell lymphoma (DLBL). DNA was extracted from tumour cells micro-dissected from paraffin- embedded tissue sections in 24 patients with FL and subsequent transformation to DLBL and 18 patients with de novo DLBL. Tumour DNA was compared to reference DNA using comparative genomic hybridization. Abnormalities common to all 3 groups were gains on chromosomes 4q, 5q, 7q, 11q and X and losses on 3p, 8p and 10q. Copy number changes seen in both transformed and de novo DLBL and not seen in FL were gains on 2p and losses on 1q, 15q and Xq. Gains on 2q, 6p, 7p and 17q and losses on 5p and 8q were specific to transformed DLBL cases. Gain on 12q12-14 was found in 52% of the transformed DLBL cases and was never seen in its follicular counterpart. Patterns of genomic copy number change associated with specific clinical events in NHL have been demonstrated and suggest that gains on 2q, 6p, 7p, 12q and 17q and losses on 5p and 8q may be important in the transformation from low to high-grade disease. PMID- 11207047 TI - Expression of individual lamins in basal cell carcinomas of the skin. AB - In this study we used a unique collection of type specific anti-lamin antibodies to study lamin expression patterns in normal human skin and in skin derived from patients with basal cell carcinomas (BCCs). Lamin expression in serial sections from frozen tissue samples was investigated by single and double indirect immunofluorescence. In normal skin, lamin A was expressed in dermal fibroblasts and in suprabasal epithelial cells but was absent from all basal epithelial cells. Lamin C was expressed in dermal fibroblasts, suprabasal epithelial cells and a majority of basal epithelial cells. However, lamin C was not expressed in quiescent basal epithelial cells. Lamin B1 was expressed in all epithelial cells but was not expressed in dermal fibroblasts. Finally, lamin B2 was expressed in all epithelial cells but was not expressed in dermal fibroblasts. Finally, lamin B2 was expressed in all cell types in normal skin. Lamin expression was also investigated in a collection of 16 BCCs taken from a variety of body sites. Based upon patterns of lamin expression the BCCs were classified into four groups: A negative (10/16 tumours), C-negative (5/16 tumours), A/C-negative (1/16 tumours) and A/B2-negative (1/16 tumours). Lamin expression was also compared to cell proliferation index by staining serial sections with the proliferation marker Ki67. 9/10 of the lamin A negative tumours were highly proliferative, whereas 4/5 of the lamin C negative tumours were slow growing. Thus as a general rule absence of lamin A was correlated with rapid growth within the tumour, while absence of lamin C was correlated with slow growth within the tumour. Our data supports the hypothesis that lamin A has a negative influence on cell proliferation and its down regulation may be a requisite of tumour progression. PMID- 11207046 TI - Telomerase activation cooperates with inactivation of p16 in early head and neck tumorigenesis. AB - Alteration of the p16/pRb pathway may cooperate with telomerase activation during cellular immortalization and tumour progression. We studied p16 expression status by immunohistochemistry and telomerase activity using the TRAP assay in 21 premalignant lesions of the head and neck epithelium as well as 27 squamous-cell carcinomas. We also examined expression of other components of the pathway (cyclin D1 and pRb) as well as presence of human papillomavirus genomes which can target these molecules. 4 of 9 mild dysplastic lesions (44%), 8 of 12 moderate/severe dysplastic lesions (67%), and 25 of 27 squamous-cell carcinomas (92%) demonstrated high telomerase activity (P = 0.009). There was a parallel increase with severity of lesions for the trend in proportions of cases demonstrating p16 inactivation or cyclin D1 overexpression (P = 0.02 and P = 0.01, respectively). For Ki67, a marker of cell proliferation, this trend was not significant (P = 0.08). Human papillomavirus infection was only found in 4 cases among the 48 samples tested (8.3%). In conclusion, progression of disease is accompanied by a parallel and continuous increase in telomerase activity and alterations in cell cycle regulators (p16, cyclin D1), as proposed by in vitro models. PMID- 11207048 TI - Transcriptional down-regulation of the retinoblastoma protein is associated with differentiation and apoptosis in human colorectal epithelial cells. AB - The aim of this study was to investigate the regulation of Rb protein expression in relation to increased differentiation and induction of apoptosis in colonic epithelial cells. In vivo, Rb protein expression was found to be down-regulated towards the top of the normal colonic crypt, coincident with the region of differentiation and apoptosis, but highly expressed in colonic carcinoma tissue. Using in vitro models to study the regulation of Rb expression in pre-malignant colonic epithelial cells, we have been able to show for the first time that Rb protein expression is transcriptionally down-regulated in differentiated pre malignant cells (in post-confluent cultures) but not in malignant colorectal epithelial cells. Furthermore, suppression of rb protein function by the HPV-E7 viral oncoprotein increased both spontaneous and DNA damage-induced apoptosis. These results suggest that Rb is able to act as a survival factor in colonic epithelial cells by suppressing apoptosis, and that over-expression of pRb in colorectal tumour cells can cause a loss of sensitivity to apoptotic signalling, resulting in aberrant cell survival and resistance to therapy. PMID- 11207049 TI - The level of manganese superoxide dismutase content is an independent prognostic factor for glioblastoma. Biological mechanisms and clinical implications. AB - We address the issue of the role of manganese superoxide dismutase in tumorigenesis by studying a relatively homogeneous group of tumours for the correlation between amount of this anti-oxidant enzyme and prognosis. The clinical outcome of 30 patients affected by glioblastomas whose manganese superoxide dismutase content had been established at the time of first diagnosis is compared. When the survival of patients is stratified according to manganese superoxide dismutase level in the tumour, a link of these levels and prognosis can be observed. Patients with high levels of manganese superoxide dismutase show a median survival time of 6.11 months, while patients whose tumours display a low amount of MnSOD have a median survival time of 12.17 months. To assess the upstream mechanisms that sustain the increase in manganese superoxide dismutase content in brain neuroepithelial tumours, we also studied the expression of p53 in a series of 17 astrocytomas of various grading. In all tested astrocytomas, high manganese superoxide dismutase content is associated with cytoplasmic accumulation of p53. Thus glioblastomas can be divided into two distinct groups on the basis of their content of manganese superoxide dismutase, having 'better' or 'worse' prognosis, respectively. The use of this protein as a marker may help to define therapeutic strategies in the clinical management of glioblastoma. PMID- 11207050 TI - Malignant melanoma is genetically distinct from clear cell sarcoma of tendons and aponeurosis (malignant melanoma of soft parts). AB - Clear cell sarcoma of tendons and aponeuroses (malignant melanoma of soft parts) and conventional malignant melanoma may demonstrate significant morphologic overlap at the light microscopic and ultrastructural level. Consequently, the clinically relevant distinction between primary clear cell sarcoma and metastatic melanoma in the absence of a known primary cutaneous, mucosal or ocular tumour may occasionally cause diagnostic problems. A balanced translocation, t(12;22)(q13;q13), which can be detected, amongst others, using the reverse transcriptase polymerase chain reaction (RT-PCR) or fluorescent in situ hybridization (FISH), has been identified in a high percentage (50-75%) of clear cell sarcomas and is presumed to be tumour specific. Whether this chromosomal rearrangement is present in malignant melanoma has, to date, not as yet been studied by molecular genetic or molecular cytogenetic techniques. Using RT-PCR and FISH, a series of metastases from 25 known cutaneous melanomas and 8 melanoma cell lines (5 uveal and 3 cutaneous) were screened for the t(12;22)(q13;q13) translocation. Primers for RT-PCR were chosen based upon published breakpoint sequences. The Cosmids G9 and CCS2.2, corresponding to the 5' region of EWS and 3' region of ATF-1 respectively, were used as probes. The translocation was not identified in any of the melanomas or melanoma cell lines analysed in this study; in contrast this translocation was identified in 3 out of 5 clear cell sarcomas using these techniques. This allows distinction between translocation positive cases of clear cell sarcoma and malignant melanoma at a molecular genetic level. Consequently, in diagnostically challenging cases, this represents a valuable tool for the clinicopathologic differentiation between these two entities, with an important impact on patient management and prognosis. PMID- 11207051 TI - Histological type and marker expression of the primary tumour compared with its local recurrence after breast-conserving therapy for ductal carcinoma in situ. AB - We have investigated primary ductal carcinomas in situ (DCIS) of the breast and their local recurrences after breast-conserving therapy (BCT) for histological characteristics and marker expression. Patients who were randomized in the EORTC trial 10853 (wide local excision versus excision plus radiotherapy) and who developed a local recurrence were identified. Histology was reviewed for 116 cases; oestrogen and progesterone receptor status, and HER2/ neu and p53 overexpression were assessed for 71 cases. Comparing the primary DCIS and the invasive or non-invasive recurrence, concordant histology was found in 62%, and identical marker expression in 63%. Although 11% of the recurrences developed at a distance from the primary DCIS, nearly all these showed the same histological and immunohistochemical profile. 5 patients developed well-differentiated DCIS or grade I invasive carcinoma after poorly differentiated DCIS. Although these recurrences occurred in the same quadrant as the primary DCIS, they may be considered as second primary tumours. Only 4 patients developed poorly differentiated DCIS or grade III invasive carcinoma after well differentiated DCIS. We conclude that in most cases the primary DCIS and its local recurrence are related histologically or by marker expression, suggesting that local recurrence usually reflects outgrowth of residual DCIS; progression of well differentiated DCIS towards poorly differentiated DCIS or grade III invasive carcinoma is a non-frequent event. PMID- 11207052 TI - Oestrogen receptor beta expression and depth of myometrial invasion in human endometrial cancer. AB - We assessed the relative expression of oestrogen receptor (ER)alpha and oestrogen receptor (ER)beta mRNAs in 36 human endometrial cancers using a multiplex polymerase chain reaction (PCR). To determine whether or not the expression of ER subtypes in endometrial cancers is associated with clinicopathological parameters, we examined correlations between ER subtypes and age, tumour grade and depth of myometrial invasion. Using multiple regression analysis, myometrial invasion showed a significant correlation with ER-beta: ER-alpha ratio (r = 0.54, P = 0.0007). The ER-beta:ER-alpha ratio was high in advanced invasive carcinoma. Western blotting analysis showed that ER-beta proteins were highly expressed in comparison with ER-alpha proteins in endometrial cancer with severe myometrial invasion. Our results suggest that ER-beta is important in the progression of myometrial invasion. PMID- 11207053 TI - A novel doxorubicin-glucuronide prodrug DOX-GA3 for tumour-selective chemotherapy: distribution and efficacy in experimental human ovarian cancer. AB - The doxorubicin (DOX) prodrug N-[4-doxorubicin-N-carbonyl (oxymethyl) phenyl] O beta-glucuronyl carbamate (DOX-GA3) was synthesised for specific activation by human beta-glucuronidase, which is released in necrotic areas of tumour lesions. This novel prodrug was completely activated to the parent drug by human beta glucuronidase with V(max)= 25.0 micromol x min(-1) x mg(-1) and K(m) = 1100 microM. The pharmacokinetics and distribution of DOX-GA3 in nude mice bearing human ovarian cancer xenografts (OVCAR-3) were determined and compared with DOX. Administration of DOX at 8 mg x kg(-1) i.v. (maximum tolerated dose, MTD) to OVCAR-3-bearing mice resulted in a peak plasma concentration of the drug of 16.4 microM (t = 1 min). A 7.6-times lower peak plasma concentration of DOX was measured after injection of DOX-GA3 at 250 mg x kg(-1) i.v. (50% of MTD). In normal tissues the prodrug showed peak DOX concentrations that were up to 5-fold (heart) lower than those found after DOX administration. DOX-GA3 activation by beta-glucuronidase in the tumour yielded an almost 5-fold higher DOX peak concentration of 9.57 nmol x g(-1) (P< 0.05) than the peak concentration of only 2.14 nmol x g(-1) observed after DOX. As a consequence, the area under the curve of DOX calculated in tumour tissue after DOX-GA3 (13.1 micromol x min(-1) x g( 1)) was 10-fold higher than after DOX (1.31 micromol x min(-1) x g(-1)). The anti tumour effects of DOX-GA3 and DOX were compared at equitoxic doses in OVCAR-3 xenografts at a mean tumour size of 125 mm(3). The prodrug given i.v. at 500 mg x kg(-1) weekly x 2 resulted in a maximum tumour growth inhibition of 87%, while the standard treatment with DOX at a dose of 8 mg x kg(-1) i.v. weekly x 2 resulted in a maximum tumour growth inhibition of only 56%. Treatment with DOX GA3 was also given to mice with larger tumours containing more necrosis. For tumours with a mean size of 400 mm(3) the specific growth delay by DOX-GA3 increased from 2.7 to 3.9. Our data indicate that DOX-GA3 is more effective than DOX and suggest that the prodrug will be specifically advantageous for treatment of advanced disease. PMID- 11207054 TI - Human bladder cancer invasion model using rat bladder in vitro and its use to test mechanisms and therapeutic inhibitors of invasion. AB - As well as being a passive support, the extracellular matrix also regulates key biological processes such as invasion, differentiation and angiogenesis. We have therefore developed an in vitro model of bladder cancer invasion using de epithelialized rat bladder to allow for tumour cell-extracellular matrix interactions. Onto this we have seeded a panel of human bladder cancer cell lines (RT4, RT112, 253J and EJ28 (T24)) representing progression from well to poorly differentiated phenotypes and used as models of superficial to invasive bladder cancer. The better differentiated cell lines RT4 and RT112 reproducibly grew as stratified epithelium, whereas poorly differentiated EJ28 cells invaded across a broad front. Invasion was not simply related to proliferation rate, measured either as doubling time on plastic (non-invasive 253J and invasive EJ28 having the same doubling time) or by Ki-67 proliferation index within the model. We used the model to test the ability of 4 compounds that interfere with tumour cell extracellular matrix interactions (suramin, N-acetylcysteine and the urokinase plasminogen activator pathway antagonists A5 compound and monoclonal antibody Mab 3936) to inhibit invasion. At non-toxic concentrations, all significantly inhibited invasion (P< 0.05), although to varying degrees, suramin and A5 almost completely and N-acetylcysteine the least. In conclusion, this model shows the urokinase system is important for bladder invasion and can be used to investigate other mechanisms of bladder cancer invasion and also for the testing of intravesical drugs. PMID- 11207055 TI - Electroporation of human microvascular endothelial cells: evidence for an anti vascular mechanism of electrochemotherapy. AB - Recent studies have indicated that the antitumour effectiveness of electrochemotherapy, a combination of chemotherapeutic drugs with application of high voltage electric pulses applied to the tumour nodule (electroporation), result in a significant reduction in tumour blood flow and may therefore be mediated by an anti-vascular mechanism. The aim of this study was to evaluate the cytotoxicity of electroporation with bleomycin or cisplatin on cultured human microvascular endothelial cells (HMEC-1). The sensitivity of HMEC-1 cells to a 5 min treatment by electroporation with bleomycin or cisplatin (8 electric pulses, pulse duration 100 micros, frequency 1 Hz, electric field intensity 1400 V x cm( 1)) was compared to the sensitivity of cells treated continuously for 3 days with drugs alone. HMEC-1 cells were moderately sensitive to continuous exposure to cisplatin, but showed greater sensitivity to bleomycin. Combination of a 5 min drug exposure with electric pulses increased cytotoxicity approximately 10-fold for cisplatin and approximately 5000-fold for bleomycin. The electroporation of HMEC-1 cells with bleomycin for a 5 min exposure was approximately 250-fold better than a continuous exposure to the drug alone. The results of this study indicate that the anti-tumour action of electrochemotherapy is likely to be due, in part, to the highly sensitive response of vascular endothelial cells. Further studies are necessary to identify the determinants of endothelial response and its relationship to the anti-vascular action of electrochemotherapy in vivo. PMID- 11207056 TI - Therapy of human T-cell acute lymphoblastic leukaemia with a combination of anti CD7 and anti-CD38-SAPORIN immunotoxins is significantly better than therapy with each individual immunotoxin. AB - Severe combined immunodeficient (SCID) mice injected i.v. with the human T-ALL cell line CCRF CEM (SCID-CEM mice) develop within 50 days life-threatening multi organ growth of leukaemia cells. The development of leukaemia in SCID-CEM mice treated with three 10 microg i.v. doses of the anti-CD7 immunotoxin (IT) HB2 SAPORIN or the anti-CD38 IT OKT10-SAPORIN was significantly delayed compared with PBS sham-treated animals but 90% of animals treated with either IT eventually developed disseminated leukaemia cell growth. In contrast treatment of SCID-CEM mice with a combination of both ITs led not only to a significantly greater delay in time to leukaemia development but also in the numbers of animals remaining leukaemia free (60%). The native HB2 and OKT10 antibodies (both murine IgG1antibodies) exerted significant, though relatively weak therapeutic effects, probably mediated through an antibody-dependent cellular cytotoxicity (ADCC) mechanism. Moreover, there was no in vivo additivity of therapeutic effect when both antibodies were used in combination. Apparent, however, was that the combination of HB2-SAPORIN IT with OKT10 antibody led to an intermediate therapeutic effect that was significantly greater than that obtained when either was used alone but significantly less than that obtained when the two IT combination was utilized. This was similarly the case for the combination of OKT10-SAPORIN IT with HB2 antibody though the effect was less pronounced in this instance. This result suggests that the therapeutic effect of IT + antibody treatment results from an additivity between antibody-mediated delivery of saporin combined with a SCID mouse NK cell-mediated ADCC attack on the target cell directed through target cell bound antibody Fc engagement with FcgammaRIII on the NK cell surface. The combination of both ITs however gave the best therapeutic outcome in SCID-CEM mice probably as the result of (i) delivery of greater amounts of saporin to target CEM cells positive for both CD7 and CD38, (ii) delivery of an effective dose of saporin to CEM cells downregulated or negative for one of the target antigens and (iii) through ADCC mechanisms that interact additively with IT action. We have previously proposed that combination IT therapy would be one means of overcoming the problem of heterogeneity of antigen expression within a global tumour cell population and these additional findings support this and provide a further strengthening of the rationale for employing cocktails of ITs for the treatment of human malignancies. PMID- 11207059 TI - The pharmacology of phosducin. AB - The discovery of phosducin (Phd) in photoreceptor cells of the retina and the further identification of phosducin-like proteins (PhdLP) emphasizes the existence of a family of proteins characterized as cytosolic regulators of G protein functions. The individual members represent phosphoproteins with distinct tissue distributions whose highest concentrations were in the retina and the pineal gland, while lower levels were reported for tissues such as liver, spleen, striated muscle, and the brain. Several functions of Phd and PhdLP have been suggested, but their most important ability appears to be their high affinity sequestration with G betagamma subunits of heterotrimeric G proteins. This finding suggests that neutralization of G betagamma by Phd effectively impedes G protein-mediated signal transmission, since G alpha cannot reassemble with G betagamma to provide a functional G protein trimer (G alphabetagamma). Thus, it is the scavenger quality of Phd that is hypothesized to diminish intracellular communication simply by reducing the number of G proteins. An additional important function of Phd relates to the inhibition of G alpha subunits' inherent GTPase. The ability of Phd to directly bind G alpha subunits is probably of minor significance as the affinity between both proteins is low. In general, similar mechanisms have been reported for PhdLPs. In the majority of investigations concerning the interference of Phd with physiological mechanisms, the dark/light adaptation of retinal photoreceptor cells has been the most frequently studied aspect of Phd. More recently, Phd was associated with the adenylyl cyclase of olfactory cilia, as in the presence of the phosphoprotein an increased concentration of cAMP is observed. This finding is in line with the experimental outcome of permanent cell lines transfected to overexpress Phd, which exhibit sensitization to excitatory acting PGE(1), and isoproterenol, respectively. Furthermore, Phd was found to effectively slow down the mechanism of internalization of G protein-coupled opioid receptors. Pathophysiological processes associated with Phd were found for certain eye diseases. Experimental evidence suggests the development of retinal inflammation as a consequence of an autoimmunization process triggered by Phd or shorter fragments thereof. Thus, our present knowledge regarding the functions of members of the Phd family is limited currently to their control of G protein-mediated intracellular signal transmission, the process of endocytosis, and certain autoimmune diseases of the uvea and the pineal gland. However, recent information regarding the presence of certain members of the Phd family in the cell nucleus may bear new insights into the function of these compounds. PMID- 11207057 TI - Ternary combination of irinotecan, fluorouracil-folinic acid and oxaliplatin: results on human colon cancer cell lines. AB - A marked antitumour efficacy is currently obtained by oxaliplatin (LOHP) fluorouracil (FU)-folinic acid (FA) combination and by CPT11-FU-FA combination. Logically, the triple association LOHP, CPT11 and FUFA will be soon tested in cancer patients. The aim of the present study was to compare two schedules combining SN38 (the active metabolite of CPT11, irinotecan) with FU-FA and LOHP. The two schedules differed by the SN38 position. The relative contribution of each drug in the resulting global cytotoxicity was evaluated. Two human colon cancer cell lines were used (WIDR and SW620 both p53 mutated). LOHP plus FA were applied for 2 h, just before a 48 h FU exposure. The SN38 sequence was applied for 24 h, starting either 48 h before LOHP-FA (schedule A), or just after LOHP-FA exposure (schedule B). Cytotoxicity was assessed by the 3-(4,5-demethylthiazol-2 yl)-2,5 diphenyltetrazolium bromide (MTT) test and drug interactions were analysed according to the Chou and Talalay method, based on the computation of a combination index (CI). The SN38 position significantly induces a shift from additivity-antagonism when SN38 was applied after LOHP, towards additivity synergism when SN38 was applied first (P = 0.03). The relative contribution (RC) of each drug in the overall cytotoxicity of the triple combination was defined as the drug concentration giving 50% cell lethality (IC(50)) of the double association without that drug divided by the IC(50)of the triple association. Whatever the SN38 position, the larger contribution was made by LOHP (median RC = 2.4) and the smaller by SN38 (median RC = 1.1). In addition, the contribution of FUFA was improved when SN38 was applied first (median RC = 2.2) as compared to the opposite schedule (median RC = 1.2). Results were in agreement between the two explored cell lines. The present data should be taken into account when establishing the rationale of future trials combining CPT11, LOHP and FU-FA. PMID- 11207060 TI - Bombycis corpus extract prevents amyloid-beta-induced cytotoxicity and protects superoxide dismutase activity in cultured rat astrocytes. AB - Bombycis corpus(BC) or Bombyx Batryticatus, a batryticated silkworm and white stiff silkworm, is a drug consisting of the dried larva of silkworm, Mobyz mori L., dead and stiffened due to the infection of Beauveria (Bals.) Vuill. In the present study, we have examined the protective effect of the water extracts against Amyloid- beta(A beta) 25-35 peptide-induced cytotoxicity by microscopic observation and LDH assay, and its action on antioxidative enzymes using cultured astrocyte cells. A beta 25-35-induced cell death was protected by the application of water extract of BC in a dose-dependent manner, and concentrations of 10(-6)to 10(-7)g ml(-1)showed a significant effect compared to exposure of A beta 25-35 alone. When antioxidative enzyme activities such as catalase, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione-S transferase (GST) were assayed after A beta 25-35 treatment, most enzyme activities were decreased in a similar fashion. BC treatment of A beta 25-35-treated astrocytes did not affect the enzyme activities of catalase, GSH-Px and GST. However, only SOD activity was enhanced by BC treatment and this may result from the potentiation of the antioxidative ability of BC. The protective effect of BC against cytotoxicity induced by Abeta 25-35 strongly indicates that BC could be a protective agent for free radical generating compounds, and that Abeta 25-35 is not only a potent lipid peroxide inducer, but can also cause changes in antioxidative enzymes. From the results, it was concluded that BC has a protective effect against Abeta -induced cytotoxicity in cultured astrocyte cells through the inhibition of lipid peroxidation and protection of antioxidative enzymes. PMID- 11207061 TI - The ameliorating effect of the water layer of Fructus Schisandrae on cycloheximide-induced amnesia in rats: interaction with drugs acting at neurotransmitter receptors. AB - Our previous study indicated that the water layer present in Fructus Schisandra(FS(w)) at 10 and 25 mg kg(-1)significantly counteracted cycloheximide (CXM)-induced amnesia. Therefore, the mechanism of action of the ameliorating effect of FS(w)on CXM-induced amnesia in the passive avoidance task was investigated in rats. The ameliorating effect of FS(w)on CXM-induced amnesia was depressed by scopolamine. The serotonin releaser, p -chloroamphetamine significantly antagonized the ameliorating effect of FS(w)on CXM-induced amnesia. Furthermore, the ameliorating effect was also inhibited by the 5-HT(1A)receptor agonist 8-OH-DPAT, but potentiated by the 5-HT(2)receptor antagonist ritanserin. Finally, the GABA(A)receptor antagonist bicuculline blocked the ameliorating effect of FS(w). These results suggest that the beneficial effect of FS(w)on CXM induced amnesia is amplified by treatment with serotonergic 5-HT(2)receptor antagonists, but reduced by serotonergic 5-HT(1A)receptor agonists as well as GABA(A)and cholinergic receptor antagonists. PMID- 11207062 TI - Teprenone promotes the healing of acetic acid-induced chronic gastric ulcers in rats by inhibiting neutrophil infiltration and lipid peroxidation in ulcerated gastric tissues. AB - Teprenone, an anti-ulcer drug, has been reported to promote the healing of acetic acid-induced chronic gastric ulcers in rats by stimulating gastric mucus synthesis and secretion. Recently, it has been implicated that neutrophil infiltration and lipid peroxidation in ulcerated gastric tissues have an inhibitory effect on the healing of acetic acid-induced chronic gastric ulcers in rats. Therefore, we attempted to clarify whether teprenone exerts a healing promoting effect on acetic acid-induced chronic gastric ulcers through its inhibitory effect on neutrophil infiltration and lipid peroxidation in ulcerated gastric tissues. In rats with chronic gastric ulcers made by applying acetic acid to the stomach, gastric ulcer healing started later than 3 days after the acetic acid application. Gastric mucosal myeloperoxidase (MPO) activity, an index of tissue neutrophil infiltration, and lipid peroxide content were higher in the ulcerated region than in the intact region on the 8th, 15th, and 22nd day after the acetic acid application. Gastric mucosal non-protein SH content was lower in the ulcerated region than in the intact region on the 8th, 15th, and 22nd day after the acetic acid application, and gastric mucosal adherent mucus content was lower in the ulcerated region than in the intact region on the 8th and 15th day. Daily oral administration of teprenone (100 mg kg(-1)x 2) for 7 or 14 days, starting on the 8th day after the application of acetic acid to the stomach, enhanced the reduction of the ulcer area with attenuation of all these biochemical changes found in the ulcerated region. The teprenone administration caused a decrease in MPO activity and an increase in adherent mucus content in the gastric mucosa of the intact region. These results suggest that the healing promoting effect of teprenone on acetic acid-induced chronic gastric ulcers in rats could be due not only to stimulation of gastric mucus secretion but also to inhibition of neutrophil infiltration and enhanced lipid peroxidation in the ulcerated gastric tissue. PMID- 11207063 TI - A comparative study of policosanol vs lovastatin on intimal thickening in rabbit cuffed carotid artery. AB - Policosanol is a cholesterol-lowering drug isolated from sugar cane wax, which acts by inhibiting cholesterol biosynthesis. Previous studies have demonstrated that policosanol inhibited smooth muscle cell (SMC) proliferation in the cuffed carotid artery of the rabbit and in arterial wall damage induced by forceps in the central artery of the ear of rabbits. The present study was undertaken to compare the effects of policosanol and lovastatin on SMC proliferation in the cuffed carotid artery of rabbits. Collars were placed around the left carotid for 7 and 15 days. The contralateral artery was sham operated. We studied eight experimental groups: two controls groups receiving vehicle for 7 and 15 days, respectively, a satellite sham operated control group, four groups treated with policosanol at 5 and 25 mg kg(-1)for 7 and 15 days and a reference group receiving lovastatin at 20 mg kg(-1)for 15 days. Samples of arteries were examined by light and electron microscopy. To evaluate intimal thickening the cross-sectional areas of intima and media were measured. Neointima was significantly reduced in treated animals compared with controls, but the reduction in lovastatin animals was significantly lower than in policosanol treated groups. The SMC proliferation was studied by the immunohistochemical detection of proliferating cell nuclear antigen and the reduction observed in policosanol-treated rabbits was significantly larger than in lovastatin-treated animals. It is concluded that the protective effect of policosanol against neointima formation in this experimental model was slightly better than that of lovastatin. PMID- 11207064 TI - Possible role of nitric oxide and mast cells in endotoxin-induced cardioprotection. AB - The present study is designed to investigate the role of nitric oxide (NO) and cardiac mast cells in the cardioprotective effect of endotoxin in isolated rat heart subjected to 30 min of global ischaemia and 30 min of reperfusion. Endotoxin (2.5 mg kg(-1); i.p.) was administered 8 h before subjecting the heart to global ischaemia. Endotoxin pretreatment markedly reduced the release of lactate dehydrogenase (LDH) and creatine kinase (CK), markers of cardiac injury, in coronary effluent and the percentage incidence of ventricular premature beats (VPBs) and ventricular tachycardia/fibrillation (VT/VF) during the reperfusion phase. Endotoxin pretreatment significantly increased the release of nitrite prior to and after global ischaemia. On the other hand, endotoxin pretreatment decreased the release of mast cell peroxidase (MPO) during the reperfusion phase. The cardioprotective and antiarrhythmic effect of endotoxin pretreatment was abolished by dexamethasone (3 mg kg(-1); i.p.) or l -canavanine (20 mg kg(-1); i.p.) given 1 h before the administration of endotoxin. It is proposed that the cardioprotective and antiarrhythmic effect of the endotoxin may be ascribed to the induction of nitric oxide synthase (NOS) and subsequent increase in the release of NO. NO may stabilize cardiac mast cells and consequently decrease the release of cytotoxic mediators from these cells. Prevention of degranulation of cardiac mast cells may be responsible for the cardioprotective and antiarrhythmic effects of the endotoxin. PMID- 11207065 TI - AMPA-receptor blockade within the RVLM modulates cardiovascular responses via glutamate during peripheral stimuli. AB - We investigated the effects of AMPA-receptor blockade in the rostral ventrolateral medulla (RVLM) on cardiovascular responses and extracellular concentrations of glutamate during two different types of stimuli that activate peripheral Adelta - and C-fiber polymodal nociceptors using anesthetized rats. First, mechanical stimulation was achieved by applying a bilateral hindpaw pinch for 5 s, and second, thermal stimulation was evoked by immersing bilaterally the hindpaw metatarsi in a 52 degrees C hot water bath for 4 s. Mechanical stimulation increased mean arterial pressure (MAP) by 23 +/- 1 mmHg and heart rate (HR) by 25 +/- 3 bpm (n= 8). Thermal stimuli increased MAP by 32 +/- 3 mmHg and HR by 27 +/- 4 bpm (n= 8). After controlled generation of mechanical or thermal stimulation, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 1.0 microM) was microdialysed bilaterally into the RVLM for 30 min. Administration of CNQX attenuated MAP and HR responses during a subsequent mechanical but not during thermal stimulation. Analyses of extracellular concentrations of glutamate within the RVLM bilaterally revealed an increase of this neurotransmitter within the RVLM during mechanical noxious stimulation. Concomitant with attenuation of the cardiovascular responses, glutamate concentrations were also decreased during the mechanical stimulation after administration of CNQX. These results demonstrate that the AMPA-receptor blockade within the RVLM that attenuates cardiovascular responses during mechanical stimulation is associated with a reduction in extracellular levels of glutamate. In addition, it appears that AMPA receptors in the RVLM do not play a role in mediating cardiovascular responses during thermal stimulation. PMID- 11207066 TI - Lazaroid compounds prevent early but not late stages of oxidant-induced cell injury: potential explanation for the lack of efficacy of lazaroids in clinical trials. AB - Earlier in vitro studies demonstrated the remarkable potency of the lazaroid compounds to prevent oxidant-induced early cell injury. However, the ability of lazaroid compounds to limit oxidative injury in vivo(including renal ischemia reperfusion) has been less certain, and the early clinical trials using lazaroids to limit CNS injury or organ injury in the setting of transplantation have not been promising. Lazaroid compounds are potent inhibitors of lipid peroxidation, and their inability to influence other key injury processes, particularly during the late stages of cell injury, might partly explain the limited clinical efficacy. To test this, renal tubular (LLC-PK1) cells were incubated with 250 micromH(2)O(2)for 135 min, in the presence or absence of 2-methyl aminochroman (2 MAC, U-83836E), a lazaroid with potent ability to inhibit lipid peroxidation, or desferrioxamine, (DFO) an iron chelator with broader antioxidant efficacy. Cell injury, lipid peroxidation, DNA damage and ATP depletion were measured in the early (immediately after H(2)O(2)incubation) and late (24 h after H(2)O(2)incubation) stages of cell injury. In the early stage, 2-MAC suppressed H(2)O(2)-induced lipid peroxidation and LDH release, but not the DNA damage, ATP depletion or loss of cell replication. In contrast, DFO suppressed all of the measurements. In the late stages, despite continued suppression of lipid peroxidation, only DFO maintained significant cytoprotection against H(2)O(2), and this was accompanied by reduced DNA damage, higher ATP levels and preservation of cell proliferation. Thus, the inability of the lazaroid compound 2-MAC to sustain cytoprotection in the later stages of cell injury might provide at least a partial explanation for the inefficiency of lazaroids to limit tissue injury in clinical and certain in vivo settings. PMID- 11207067 TI - Induction of heme oxygenase-1 by Ginkgo biloba extract but not its terpenoids partially mediated its protective effect against lysophosphatidylcholine-induced damage. AB - In this study, we examined whether Ginkgo Biloba Extract and its terpenoid constituents protect against oxidative stress through actions on heme oxygenase (HO) gene expression and activity. HO-1 and glutathione peroxidase (GPx) gene expressions were examined by reverse transcription polymerase chain reaction (RT PCR) analysis, HO activity and GPx enzyme activity were analysed by spectrophotometric assay. Pretreatment of H9c2 myocytes with 100-500 microgml( 1)Ginkgo Biloba Extract caused induction of HO-1 gene expression and a significant increase in HO activity; 30 microgml(-1)ginkgolide B and 30 microgml( 1)bilobalide had little effect. Treatment with Ginkgo Biloba Extract for 24 h also significantly increased GPx gene expression and GPx enzyme activity. Pretreatment with Ginkgo Biloba Extract, ginkgolide B and bilobalide protected myocytes against lysophosphatidylcholine (LPC)-induced damage. The protective effect of Ginkgo Biloba Extract against LPC-induced damage was partially suppressed by a HO inhibitor, Zinc protoporphyrin-IX (ZnPP-IX), while ZnPP-IX did not suppress the protective effect of ginkgolide B or bilobalide. Furthermore, pretreatment with hemin, biliverdin or bilirubin reduced cytotoxicity induced by LPC. These results suggest that induction of HO-1 by Ginkgo Biloba Extract but not its terpenoid constituents may play a beneficial role in oxidative stress. The mechanism of Ginkgo Biloba Extract-induced HO-1 gene expression and the increase in HO activity may be related to alteration of intracellular glutathione levels. PMID- 11207068 TI - Immunotoxicity of cupravit and previcur fungicides in mice. AB - Female mice received either cupravit or previcur at dose levels of 300 ppm and 1000 ppm, respectively, for 8 weeks. Humoral immune response was evaluated by measuring the plaque-forming cell (PFC) response and hemolysing antibody titers against sheep red blood cells (SRBCs), a T lymphocyte-dependent antigen. In addition, the hemagglutinating antibody titers against Escherichia coli lipopolysaccharide (LPS), a T cell-independent antigen, were determined. Both cupravit and previcur suppressed the PFC response by 74% and 78% of control values, respectively. The primary hemolysin antibody titers were reduced to 62% and 76% of control values, respectively. The hemagglutinating antibody titers were decreased to 66% and 77% of control values, respectively. Memory function was reduced as evidenced by inhibition of secondary hemolysin titers to SRBCs. Cell-mediated immunity was inhibited by both cupravit and previcur as evidenced by reduced delayed-type hypersensitivity (DTH) reaction to tuberculin to 77% and 76% of control values, respectively. Decreases in total leukocytic and lymphocytic counts were recorded together with histopathological changes in spleen and thymus gland of intoxicated animals. PMID- 11207069 TI - Effect of oral selenium administration on cisplatin-induced nephrotoxicity in rats. AB - Cis -diamminedichloroplatinum(II) (CP), an important antineoplasic drug, shows remarkable toxicity to the kidney. Methods to reduce CP nephrotoxicity include the use of sodium selenite. The aim of the present study was to investigate the interaction between orally administered selenium and CP in the rat. After observing the effects of CP on body growth rate, urinary volume, serum creatinine, serum selenium levels, creatinine clearance, renal malondialdehyde, and glutathione levels, as well as on renal light microscopically visible lesions, the effects of the sodium selenite administration by gavage of 2 mg per kg of body wt. 24 h and 1 h prior to a single CP intraperitoneal injection of 5 mg per kg of body wt. followed by its daily administration for the 7 subsequent days on these parameters, were examined. CP increased renal malondialdehyde, renal glutathione, and serum creatinine and decreased creatinine clearance. Lipid peroxidation is one of the mechanisms by which CP induces renal damage. Selenium treatment decreased the effect of CP on serum creatinine, and renal malondialdehyde levels, but did not affect the other parameters with the exception of kidney necrosis which was also diminished by this treatment. PMID- 11207070 TI - Inhibition of the NANC relaxation of the guinea-pig proximal colon longitudinal muscle by the purinoceptor antagonist PPADS, inhibition of nitric oxide synthase, but not by a PACAP/VIP antagonist. AB - The effects of the P(2)-purinoceptor antagonist pyridoxal-phosphate-6-azophenyl- 2('),4(')- disulphonic acid (PPADS), the nitric oxide (NO) synthase inhibitor N(G)-nitro- l -arginine (l -NOARG), the K(+)-channel blocker apamin, the pituitary adenylate cyclase activating peptide (PACAP) antagonist PACAP(6-38) and the sensory neuron-blocking drug capsaicin were examined on the non-adrenergic, non-cholinergic (NANC) relaxation evoked by electrical field stimulation in the longitudinal muscle of the guinea-pig proximal colon. Both PPADS (50 microm) and l -NOARG (100 microm) significantly inhibited the NANC relaxation. In the presence of l -NOARG, PPADS inhibited and apamin (100 nm) practically abolished the response. Capsaicin slightly but significantly enhanced the NANC relaxation at 10, but not at 1 Hz stimulation frequency. PACAP(6-38) (3 microm) had no effect on the NANC relaxation, although it abolished the relaxant effect of exogenous PACAP(1-27) (10 nm) and reduced that of exogenous vasoactive intestinal polypeptide (VIP, 30-100 nm) by about 60 %. PPADS (50 microm) inhibited the relaxant action of exogenous adenosine 5(')-triphosphate (ATP; 1 and 10 microm), the inhibition being stronger at 1 microm ATP. These data indicate that an exogenous P(2)-purinoceptor stimulant (possibly ATP) and NO are involved in the NANC relaxation of the guinea-pig colon. The 'non-nitrergic' apamin-sensitive component of the response might also include an unidentified transmitter. No evidence has been found for a mediating role of PACAP/VIP-like peptides. PMID- 11207071 TI - Effect of A. lanata leaf extract and Vediuppu chunnam on the urinary risk factors of calcium oxalate urolithiasis during experimental hyperoxaluria. AB - Urolithiasis is one of the third most common afflictions found in humans. The efficacy of the two Siddha drugs, Aerva lanata and Vediuppu chunnam as antilithic agents using a urolithic rat model were tested in this study. Hyperoxaluria was induced in rats using 0.75% ethylene glycol in drinking water. Aerva lanata(3.0 mg kg(-1)body weight) and Vediuppu chunnam (3.5 mg kg(-1)body weight) were given orally for 28 days. Urinary risk factors of urolithiasis were monitored at the end of 7th, 14th, 21st and 28th days. Urinary volume was increased in hyperoxaluric as well as drug-treated rats. Increased urinary excretion of calcium, oxalate, uric acid, phosphorus and protein in hyperoxaluric rats was brought down significantly by the administration of A. lanata or Vediuppu chunnam. Decreased magnesium excretion in hyperoxaluric rats was normalized by drug treatment. The drug increases the urine volume, thereby reducing the solubility product with respect to calcium oxalate and other crystallizing salts such as uric acid, which may induce epitaxial deposition of calcium oxalate. Drug alone treated rats did not show any adverse effects. Combination therapy was found to be more effective and this indigenous medicine can be used successfully as an antilithic agent. PMID- 11207072 TI - Differential inhibitory mechanism of Fe2+ and Fe3+ on contraction of ileal longitudinal smooth muscle. AB - The mechanism of the inhibition of K(+)-induced contraction caused by ferrous (Fe(2+)) and ferric (Fe(3+)) ions were analysed in guinea-pig ileal longitudinal muscle and taenia coli. Fe(2+)increased the threshold for Ca(2+)-induced contraction in Ca(2+)-free, K(+)-depolarized taenia coli. However, Fe(3+)reduced the size of the maximal response to Ca(2+)without shifting the dose-response curves in taenia coli. Both 10 mM Fe(2+)and 2 mM Fe(3+)caused significant decreases in Ca uptake, as determined by the La method, during K(+)-induced ileal contraction. After treatment with 10 mM Fe(2+)in a state of cell membrane depolarization with K(+)for 30 min, the ileal K(+)-induced tonic contraction was completely restored by washing with medium containing EDTA, a chelator of divalent cations, and Fe(2+)remaining in muscle was almost eliminated by washing. In contrast, after treatment with 2 mM Fe(3+)in K(+)medium, K(+)-induced contraction was reversed only to a slight degree by washing with medium containing deferoxamine, a chelator of trivalent cations, and Fe(3+)in muscle largely remained despite the washing. These results suggest that Fe(2+)binds to the ileal surface membrane and reduces the contraction in response to K(+)mainly by inhibiting Ca(2+)influx. Fe(3+)may exert an inhibitory action on intracellular sites, in addition to the interference of Ca(2+)influx at the cell membrane. PMID- 11207073 TI - High sensitivity C-reactive protein for predicting cardiovascular disease: an inflammatory hypothesis. PMID- 11207074 TI - Ionic or non-ionic contrast media during coronary intervention: does it make a difference? PMID- 11207075 TI - What should be the focus in the management of patients with heart failure? The importance of peripheral vision. PMID- 11207076 TI - The Brugada syndrome: diagnostic criteria and cellular mechanisms. PMID- 11207077 TI - Screening for drug-induced (acquired) long QT syndrome: is it time to apply new methods? PMID- 11207078 TI - The role of tilt table testing in neurocardiocascular instability in older adults. PMID- 11207079 TI - Risk of infection by reprocessed and resterilized virus-contaminated catheters; an in-vitro study. AB - AIMS: In spite of increasing reuse of disposable catheters, there are few scientific data on potential viral transmission and infection after reuse. To determine the theoretical risk of virus transmission during reuse of catheters an in vitro study was performed using an RNA virus (echovirus-11) and a DNA virus (adenovirus-2). METHODS AND RESULTS: After deliberate contamination of the catheters, reprocessing and reuse of the cleaned and glutaraldehyde sterilized catheters was simulated. The presence of residual virus was determined by cell culture and by polymerase chain reaction (PCR). After the sterilization step, infectious enterovirus was detectable in one (10%) of the samples, whereas two (20%) contained detectable enterovirus RNA. After simulated reuse, enterovirus was cultured from one (10%) of the catheters, but no less than six (60%) of the samples were enterovirus PCR positive and one (10%) contained detectable adenovirus DNA. After sonification of the catheter tips no infectious virus could be detected, but enterovirus RNA was detected in two (20%) and adenovirus DNA in three (30%) of the samples. CONCLUSIONS: It has been clearly demonstrated in this in vitro study that, even after rigorous cleaning and sterilization, virus was still present in the catheter. Reuse of catheters, labelled for single-use only, is dangerous and should be prevented. PMID- 11207080 TI - Acute and subacute stent occlusion; risk-reduction by ionic contrast media. AB - AIMS: Current data concerning the influence of X-ray contrast media on the incidence of thrombotic complications in interventional cardiology are controversial. The effect of ionic contrast media on acute (< or =72 h) and subacute (< or =30 days) stent thrombosis has not been investigated. METHODS: Three thousand, nine hundred and ninety consecutive patients underwent coronary stent placement. Group I (n=1808) received non-ionic contrast media while group II (n=2182) was given the ionic Ioxaglate. All patients were treated with a standard regimen of aspirin and ticlopidine for 4 weeks post intervention. RESULTS: Both acute and subacute stent occlusion occurred more frequently in patients receiving non-ionic contrast media compared to ionic contrast media (acute stent occlusion: 1.3% in group I vs 0.3% in group II, P=0.001; subacute stent occlusion: 2.4% in group I vs 0.7% in group II, P=0.001). The incidence of the combined clinical end-point of coronary artery bypass grafting, target lesion revascularization, and overall mortality within 12 months was significantly reduced by the use of Ioxaglate (22.9% vs 16.3%, P=0.001). CONCLUSIONS: Based upon these data, we recommend the use of Ioxaglate in coronary interventions when stent placement is anticipated. PMID- 11207081 TI - Preservation of exercise capacity and lack of peripheral changes in asymptomatic patients with severely impaired left ventricular function. AB - AIMS: To establish the extent, if any, of peripheral changes in asymptomatic patients with severe left ventricular dysfunction. METHODS ANS RESULTS: Nine asymptomatic and nine symptomatic patients with left ventricular ejection fraction, <25%, matched for age and left ventricular ejection fraction (asymptomatic vs symptomatic, age: 52+/-1.5 vs 55.9+/-2.5 years [Mean+/-SEM], left ventricular ejection fraction: 16+/-2 vs 19+/-2%P=0.23 and 0.48, respectively) were studied and compared with 26 age-matched normal controls. We assessed exercise capacity, leg blood flow (occlusion plethysmography), respiratory muscle strength, quadriceps maximal isometric strength, fatigue and CT cross-sectional muscle area at mid thigh. Fatigue was expressed as the percentage reduction in maximal strength following a 20 min fatiguing protocol. There was a graded increase in peak oxygen consumption comparing symptomatic, asymptomatic and control groups (16.6+/-1.3 vs 27.1+/-1.6 vs 32.8+/-1.3 ml x min( 1) x kg(-1)respectively, ANOVA P<0.0001). Between the three groups there was significant variation in muscle strength (P<0.0001), endurance (P=0.0002) and cross-sectional area (P=0.0003) and in peak blood flow (P=0.027) and respiratory muscle strength (P<0.05). When asymptomatic patients and controls were compared no significant differences existed. CONCLUSIONS: Patients with severe left ventricular dysfunction may have near normal exercise capacity and no peripheral changes. Exercise capacity may depend less upon left ventricular function than on the presence or absence of peripheral factors. PMID- 11207082 TI - Diagnosis and long-term follow-up of the Brugada syndrome in patients with idiopathic ventricular fibrillation. AB - AIMS: Some patients with idiopathic ventricular fibrillation may suffer from the Brugada syndrome. The diagnostic criteria for the Brugada syndrome are uncertain and arbitrarily set. Therefore, we studied the prevalence of the Brugada syndrome using various diagnostic criteria and long-term follow-up in 37 idiopathic ventricular fibrillation patients. METHODS AND RESULTS: Idiopathic ventricular fibrillation was diagnosed after thorough clinical evaluation in 37 survivors of an out-of-hospital cardiac arrest referred to our institute (UMC Utrecht). Retrospectively, nine patients (24%, group I) were classified as potentially having the Brugada syndrome based on the presence of (in)complete right bundle branch block and ST-segment elevation in leads V(1)-V(3)of > or =1 mm. Only three patients (8%, group II) showed (in)complete right bundle branch block and > or =2 mm ST-segment elevation. With the intermittent presence of these ECG features and/or their (re)appearance with class I antiarrhythmic drugs included as criteria, the percentage of the Brugada syndrome was attenuated in group I (2/37; 5%) and group II (1/37; 3%). Sixteen (43%) of all idiopathic ventricular fibrillation patients (mean follow-up 77+/-41 months) had a recurrent episode of syncope, ventricular tachyarrhythmias or sudden death. Recurrence rate was 3/9 (33%) in Brugada patients group I, 2/3 (66%) in group II and 13/28 (46%) in patients without the Brugada syndrome (P=ns). CONCLUSIONS: Depending on the diagnostic criteria used, the Brugada syndrome was observed in 3% to 24% of patients with idiopathic ventricular fibrillation, underlining the importance of defining the precise diagnostic criteria in these patients. For all idiopathic ventricular fibrillation patients, the ventricular tachyarrhythmia recurrence rate was substantial during an average follow-up of more than 6 years. PMID- 11207083 TI - Dynamic analysis of the QT interval in long QT1 syndrome patients with a normal phenotype. AB - AIMS: In families with the long QT syndrome penetrance may be low: up to 70% of gene carriers may have a normal QTc interval. These patients require therapy, similar to that in those with longer QTc intervals, but identifying them, using molecular analysis, is difficult to apply on a large scale. A large French family affected by the long QT1 syndrome was followed-up over a 25-year period. In adult males but not in females, the QTc interval normalized after puberty. We aimed to find clinical criteria, based on ambulatory ECG recordings so that we could improve diagnosis in affected members with a normal QTc. METHODS AND RESULTS: Linkage analysis and direct sequencing were an indicator of the long QT1 gene in our family. Reverse transcription-polymerase chain reaction analysis demonstrated abnormal transcripts in lymphocytes from silent gene carriers. The functional profile of mutated protein isoforms was investigated using the patch-clamp technique. Dynamic analysis of ventricular depolarization was conducted using Holter recordings in patients, and in sex- and age-matched controls. Circadian variations of the QTc interval and the QT/RR relationship were assessed. Sensitivity, specificity, and predictive values were evaluated for proposed clinical criteria. We found that dynamic analysis of the QT interval permitted individual diagnosis in mutation carriers even when the QTc interval was normal (adult males). CONCLUSION: Dynamic analysis of the QT interval is of diagnostic value in the long QT1 syndrome in patients with a normal phenotype. Clinical implications include improvement in screening and patient management. PMID- 11207084 TI - Impact of radiofrequency catheter ablation of accessory pathways on the frequency of atrial fibrillation during long-term follow-up; high recurrence rate of atrial fibrillation in patients older than 50 years of age. AB - AIMS: Atrial fibrillation represents a frequent and potentially life-threatening arrhythmia in patients with accessory atrioventricular pathways. Radiofrequency ablation has become the curative treatment of first choice for these patients. Investigations after successful surgical pathway dissection reported an almost complete elimination of paroxysmal atrial fibrillation. However, there are only a few reports which include a small number of patients undergoing radiofrequency ablation. The purpose of this study was to examine whether successful radiofrequency ablation of accessory pathways prevents the occurrence of paroxysmal atrial fibrillation, and to identify possible predictors of atrial fibrillation recurrence. METHODS AND RESULTS: A total of 116 consecutive patients (mean age 42+/-15 years) with manifest or concealed accessory pathways and documented paroxysmal atrial fibrillation underwent radiofrequency catheter ablation. The patients were reexamined at 6 and 12 months. Long-term follow-up information was obtained by questionnaire and/or by consulting the referring physician. Pathway conduction was abolished in 101 cases (87%). Late follow-up information was obtained from 91 of these 101 patients (90%) with successful ablation with a mean follow-up duration of 23.9+/-12.3 months. During follow-up, 25 of 91 patients (27%) experienced arrhythmias. Recurrent episodes of atrial fibrillation were observed in 18 of these 25 cases (i.e. 20% of the 91 patients). Differences between patients with and without recurrences of atrial fibrillation were examined for age, sex, associated cardiac disease, presence of multiple pathways, pathway location, atrial fibrillation inducibility during the procedure and cycle length of the atrioventricular reentrant tachycardia. Only older age was a significant independent predictor of atrial fibrillation recurrence (P=0.02). Eleven of 31 patients (35%) older than 50 years of age had atrial fibrillation recurrences during follow-up compared to seven of 60 patients (12%) under age 50. The recurrence rate of atrial fibrillation was even higher in patients older than 60 years (6 of 11 patients, i.e. 55%). In comparison, the occurrence rate of atrial fibrillation during follow-up in a control group of 100 consecutive patients with successful accessory pathway ablation, who did not have evidence of paroxysmal atrial fibrillation prior to ablation, was 4% and, thus, significantly lower than in the study group of the 91 patients (P=0.001). CONCLUSIONS: The recurrence rate of paroxysmal atrial fibrillation after successful radiofrequency ablation of accessory pathways shows an age-related increase, being low in patients younger than 50 years of age (12%) and high in the older patients: 35% in patients older than 50 years and 55% in patients older than 60. These results have significant therapeutic implications concerning the decisions on pharmacological therapy after successful ablation in patients older than 50 years. Furthermore, these data will help physicians advise older patients properly about their risk of recurrence of atrial fibrillation after ablation. PMID- 11207085 TI - Omega-3 fatty acids improve blood pressure control and preserve renal function in hypertensive heart transplant recipients. AB - BACKGROUND: Hypertension and cyclosporine-induced nephrotoxicity are common complications in heart transplant recipients. Omega-3 fatty acids may prevent blood pressure rise early, but have not been studied long-term after heart transplantation. METHODS AND RESULTS: Forty-five clinically stable hypertensive heart transplant recipients were studied 1-12 years after transplantation and randomized in a double-blind fashion to receive either 3.4 g of omega-3 fatty acids daily or placebo for 1 year. Ambulatory 24 h blood pressure monitoring and haemodynamic studies were performed before randomization and at the end of the study. Systolic blood pressure increased by 8+/-3 mmHg (P<0.01) in the placebo group, with a non-significant increase in diastolic blood pressure of 3+/-2 mmHg (P=0.10), accompanied by a 14% increase in systemic vascular resistance (P<0.05). In contrast, no change in blood pressure or systemic vascular resistance was recorded in the omega-3 group. Plasma creatinine increased (P<0.01) and glomerular filtration rate decreased (P<0.05) in the placebo group, while no changes were observed in the omega-3 group. The antihypertensive effect was related to an increase in serum eicosapentaenoic and docosahexaenoic acid. CONCLUSION: Treatment with omega-3 fatty acids may reduce the long-term continuous rise in blood pressure after heart transplantation and may offer a direct or indirect renoprotective effect, making these fatty acids a potentially attractive treatment for post-transplant hypertension. PMID- 11207087 TI - The risk of alcohol leakage into the left anterior descending coronary artery during non-surgical myocardial reduction in patients with obstructive hypertrophic cardiomyopathy. PMID- 11207089 TI - Kinetic analysis of a model of the sarcoplasmic reticulum Ca-ATPase, with variable stoichiometry, which enhances the amount and the rate of Ca transport. AB - The sarcoplasmic reticulum (SR) Ca-dependent adenosinetriphosphatase (Ca-ATPase) actively transports Ca2+ from the myoplasm to the SR lumen. Under optimal conditions a 2:1 stoichiometry of Ca transport/ATP hydrolysis has been observed, but lower stoichiometries have been reported under several circumstances. A lower stoichiometry under conditions of high Ca2+ load, although thermodynamically less efficient, could in theory increase the rate and the maximal amount of Ca uptake. We analysed, by computing simulation, the transient kinetics of a model of the SR Ca-ATPase with variable stoichiometry. The model is based on current experimental reports and includes the most relevant properties of the system. The results show an acceleration in the rate of Ca uptake, an increase in the net Ca transport, and an increase in the rate of [Ca2+] reduction in the medium, which might be physiologically useful to increase the rate of Ca pumping at high Ca load of the sarcoplasmic reticulum. PMID- 11207090 TI - Building the cellular puzzle: control in multi-level reaction networks. AB - Quantitative conceptual tools dealing with control and regulation of cellular processes have been mostly developed for and applied to the pathways of intermediary metabolism. Yet, cellular processes are organized in different levels, metabolism forming the lowest level in a cascade of processes. Well-known examples are the DNA-mRNA-enzyme-metabolism cascade and the signal transduction cascades consisting of covalent modification cycles. The reaction network that constitutes each level can be viewed as a "module" in which reactions are linked by mass transfer. Although in principle all of these cellular modules are ultimately linked by mass transfer, in practice they can often be regarded as "isolated" from each other in terms of mass transfer. Here modules can interact with each other only by means of regulatory or catalytic effects-a chemical species in one module may affect the rate of a reaction in another module by binding to an enzyme or transport system or by acting as a catalyst. This paper seeks to answer two questions about the control and regulation of such multi level reaction networks: (i) How can the control properties of the system as a whole be expressed in terms of the control properties of individual modules and the effects between modules? (ii) How do the control properties of a module in its isolated state change when it is embedded in the whole system through its connections with the other modules? In order to answer these questions a quantitative theoretical framework is developed and applied to systems containing two, three or four fully interacting modules; it is shown how it can be extended in principle to n modules. This newly developed theory therefore makes it possible to quantitatively dissect intermodular, internal and external regulation in multi-level systems. PMID- 11207091 TI - Heat and water rate transfer processes in the human respiratory tract at various altitudes. AB - The process of the respiratory air conditioning as a process of heat and mass exchange at the interface inspired air-airways surface was studied. Using a model of airways (Olson et al., 1970) where the segments of the respiratory tract are like cylinders with a fixed length and diameter, the corresponding heat transfer equations, in the paper are founded basic rate exchange parameters-convective heat transfer coefficient h(c)(W m(-2) degrees C(-1)) and evaporative heat transfer coefficient h(e)(W m(-2)hPa(-1)). The rate transfer parameters assumed as sources with known heat power are connected to airflow rate in different airways segments. Relationships expressing warming rate of inspired air due to convection, warming rate of inspired air due to evaporation, water diffused in the inspired air from the airways wall, i.e. a system of air conditioning parameters, was composed. The altitude dynamics of the relations is studied. Every rate conditioning parameter is an increasing function of altitude. The process of diffusion in the peripheral bronchial generations as a basic transfer process is analysed. The following phenomenon is in effect: the diffusion coefficient increases with altitude and causes a compensation of simultaneous decreasing of O(2)and CO(2)densities in atmospheric air. Due to this compensation, the diffusion in the peripheral generations with altitude is approximately constant. The elements of the human anatomy optimality as well as the established dynamics are discussed and assumed. The square form of the airways after the trachea expressed in terms of transfer supposes (in view of maximum contact surface), that a maximum heat and water exchange is achieved, i.e. high degree of air condition at fixed environmental parameters and respiration regime. PMID- 11207092 TI - Model of the carbon concentrating mechanism in chloroplasts of eukaryotic algae. AB - A generic chloroplast-based model for the carbon concentrating mechanism (CCM) in eukaryotic algae is presented. The fine structure of chloroplasts is represented by separate compartments: marginal and bulk stroma, pyrenoid, girdle lamella, bulk thylakoids, and central lamella traversing the pyrenoid. The roles of the individual structural elements of the chloroplast with respect to the CCM and the effect of carbonic anhydrase activity in various compartments are analysed. Hypothetical HCO(-)(3)transport into the acidic thylakoid lumen is adjusted by imposing an optimization principle: a given [CO(2)] at the site of RuBisCO is achieved with minimum energy costs for the CCM. Our model is highly efficient in terms of saturation of RuBisCO carboxylase activity and the affinity of the chloroplast for CO(2), if either a girdle lamella or a pyrenoid is present. The highest efficiency is achieved with a pyrenoid. A eukaryotic CCM is not necessarily associated with accumulation of dissolved inorganic carbon (DIC) as in cyanobacteria. Chloroplasts are categorized into four types corresponding to morphological characteristics of all major algal classes with regard to the presence of pyrenoids, girdle lamellae, and the distribution of CA activity. PMID- 11207093 TI - The response of a selfish herd to an attack from outside the group perimeter. AB - According to the selfish herd hypothesis, animals can decrease predation risk by moving toward one another if the predator can appear anywhere and will attack the nearest target. Previous studies have shown that aggregations can form using simple movement rules designed to decrease each animal's Domain of Danger. However, if the predator attacks from outside the group's perimeter, these simple movement rules might not lead to aggregation. To test whether simple selfish movement rules would decrease predation risk for those situations when the predator attacks from outside the flock perimeter, we constructed a computer model that allowed flocks of 75 simulated fiddler crabs to react to one another, and to a predator attacking from 7 m away. We attacked simulated crab flocks with predators of different sizes and attack speeds, and computed relative predation risk after 120 time steps. Final trajectories showed flight toward the center of the flock, but curving away from the predator. Path curvature depended on the predator's size and approach speed. The average crab experienced a greater decrease in predation risk when the predator was small or slow moving. Regardless of the predator's size and speed, however, predation risk always decreased as long as crabs took their flock-mates into account. We conclude that, even when flight away from an external predator occurs, the selfish avoidance of danger can lead to aggregation. PMID- 11207094 TI - Variability of excitatory currents due to single-channel noise, receptor number and morphological heterogeneity. AB - Patch clamp recordings of excitatory postsynaptic currents (EPSCs) in central neurons reveal large fluctuations in amplitudes and decay times of AMPA-receptor mediated EPSCs. By using Monte Carlo simulations of synaptic transmission in brainstem interneurons, we tested several hypothesis that could account for the observed variability. The coefficient of variation (CV) of 0.5 for miniature amplitudes cannot be explained by fluctuations in vesicle content or receptor distribution, but is traced to variations in receptor number, which is estimated as 77+/-39 receptors per bouton. As the variability of rise times reflects fluctuations in size of the post-synaptic density and heterogeneity of the receptor distribution, the relatively small CV=0.37 of experimentally determined values points to a homogeneous arrangement of receptors. Within our model the large variability of decay times (CV=0.49) can only be explained by fluctuations in the transmitter time course (mean residence times of 0.4+/-0.13 ms), presumably resulting from heterogeneities in synaptic morphology. Hence, our simulations indicate that different noise sources control the variability of amplitudes, rise and decay times. In particular, the distribution of decay times yields information about the synaptic transmission process, which cannot be obtained from other observables. PMID- 11207095 TI - Performance of basic strategies for following gradients in two dimensions. AB - Computer models for following stimulus gradients in two-dimensional space were evaluated to determine the relative advantages of different strategies and to identify the issues that must be addressed in making such a comparison. The simulations were implemented with emphasis on making them as general and free of specific assumptions as possible. Performance was defined as progress along the gradient divided by the cost of the movements and time taken. Plausible values of costs were taken from data on animal energetics. The models also included various kinds of noise that limit performance. These included unintended variations and biases in motor outputs as well as sensory inputs. An initial guess at appropriate noise levels led to performance worse than that observed in experiments with leukocytes. Reduced noise levels gave good agreement. Under these, more appropriate, conditions, peak performance for the various models varied from 24 to 99% of the maximum possible. The threshold gradient required to provide performance equal to 1% of the maximum possible varied from 800 to 5000 searcher diameters per gradient decay length. Some models performed well only over a narrow range of gradients. There was no indication of a tradeoff between sensitivity to shallow gradients and high performance in steep gradients. The model of tropotaxis (simultaneous, spatial comparison) with movement in any direction was superior in having the lowest threshold, the highest maximum performance, requiring the fewest parameters to fit, and performed well over the widest range of gradients. This result suggests that amoeboid cells and echinoderms might be particularly well suited to following gradients. The modeling demonstrates the need to obtain quantitative estimates for a number of parameters (relating costs and noise levels) for a more rigorous understanding of the relative advantages of these different strategies. PMID- 11207096 TI - A new method for assembling metabolic networks, with application to the Krebs citric acid cycle. AB - To understand why a molecular network has a particular connectivity one can generate an ensemble of alternative networks, all of which meet the same performance criteria as the real network. We have generated alternatives to the Krebs cycle, allowing group transfers and B(12)-mediated shifts that were excluded in previous work. Our algorithm does not use a reaction list, but determines the reactants and products in generic reactions. It generates networks in order of increasing number of reaction steps. We find that alternatives to the Krebs cycle are very likely to be cycles. Many of the alternatives produce toxic or unstable compounds and use group transfer reactions, which have unfavorable consequences. Although alternatives are better than the Krebs cycle in some respects, the Krebs cycle has the most favorable combination of traits. PMID- 11207097 TI - The role of H+ concentration on the capacitance of a membrane channel protein. PMID- 11207098 TI - Programmed cell death or cell death programme? That is the question. PMID- 11207099 TI - Political decision adversely affects women's health. PMID- 11207100 TI - Women's attitudes to being asked about exposure to violence. AB - OBJECTIVE: to examine women's attitudes to being questioned by their midwife, during and after pregnancy, about exposure to violence. DESIGN: an explorative study using content analysis of one open-ended question. SETTING: all antenatal clinics in Uppsala, a medium-sized Swedish university town. PARTICIPANTS: all women registered for antenatal care before 32 weeks of pregnancy, during a period of 6 months. MEASUREMENTS: all women were assessed regarding abuse, using the Abuse Assessment Screen (McFarlane 1993) twice during pregnancy and once again more than four weeks after the birth. On the last occasion the women were asked to respond to an open-ended written question worded: 'Please describe how you felt about being questioned by your midwife at the antenatal clinic concerning violence' Those women who reported violence and those who did not were compared regarding their attitude to being asked about violence. FINDINGS: 879 women were presented with the open-ended question. Eighty per cent found the questioning acceptable, 12% neither acceptable nor unacceptable, 5% both acceptable and unacceptable, and only 3% found it unacceptable. There was no difference between those who reported abuse and those who did not, as to whether the questioning was unacceptable. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: the findings suggest that most pregnant women are not averse to being asked, by their midwife, about exposure to violence. As part of the identification of risk factors that is carried out in every pregnancy, the midwife should ask about exposure to violence at the antenatal clinic. To feel confident when raising the subject of abuse, midwives must be taught about the nature of intimate-partner violence, and appropriate referral and intervention strategies. PMID- 11207101 TI - Breast-feeding practices among Thai women in Australia. AB - OBJECTIVE: to examine the perceptions and experience of breast-feeding practices among Thai women who are now living in Australia. DESIGN: ethnographic interviews and participant observation among Thai women in Australia. SETTING: Melbourne Metropolitan Area,Victoria, Australia. FINDINGS: Thai women see breast milk as the most valuable food for newborn babies and young children. Breast milk is seen as 'human milk', while infant formula is referred to as 'animal milk'. Breast feeding is seen as beneficial not only to babies' health, but also to the mother's health. Women consume certain foods such as drinking hot water and consuming hot soup during the confinement period as a way to ensure breast milk production. Women appear to know that 'breast is best', but some lack accurate knowledge about breast feeding. They also receive inaccurate information regarding feeding practices from health professionals. IMPLICATIONS FOR PRACTICE: there is no doubt that Thai women see that 'breast is best', therefore, the main message for those involved in giving breast-feeding advice is to 'make it easy for women to do it'. Only then can health services and care be made more meaningful to the many women who have decided to breast feed their babies in their new country. PMID- 11207102 TI - 'Giving midwifery care: student midwives' views of their working role. AB - OBJECTIVE: to explore the opinions, feelings and views of student midwives of their education as they progressed through their two-year programme in Ireland, with the intention of interpreting and understanding the working and learning world of the participants so that future students might be assisted to improve their educational experiences. DESIGN: using quantitative and qualitative methods. A phenomenological approach was used to guide the qualitative section of the study reported here. SETTING: all seven midwifery schools in Southern Ireland. PARTICIPANTS: all students in the first intake of 1995 in every midwifery school in Ireland (n = 125). DATA COLLECTION: individual and group interviews, diary-keeping and questionnaires. KEY CONCLUSIONS: the findings presented here illustrate the students' views of their working role. The environment appeared to be one of work, rather than learning, and the students' status that of junior employee rather than 'learner' They perceived themselves as 'thrown in the deep end' without much support or guidance from qualified staff. They were frightened, unsure of themselves and suffered from role conflict and loss of status. There appeared to be an acute shortage of staff and the care given was seen to be the basic minimum, fulfilling women's physical needs but ignoring their emotional ones. The care given appeared to be planned according to routine and economic necessity rather than for sound midwifery, medical or social reasons. IMPLICATIONS FOR PRACTICE: the education of students needs to focus on the development of autonomous practice and the use of routines and non-research based care should be phased out. Students need to be assisted, with support from educated mentors, to plan care in a holistic way that will enable them to develop their midwifery skills in the future. PMID- 11207103 TI - An investigation into the feasibility of comparing three management options (augmentation, conservative and water) for nulliparae with dystocia in the first stage of labour. AB - OBJECTIVE: to evaluate the feasibility of a randomised controlled trial (RCT) examining the effect of three options (augmentation, conservative and water) for the management of dystocia in nulliparae. The main objectives were to explore the feasibility of trial procedures in the clinical environment, consent rates and acceptability of the management options to women, local incidence of dystocia in nulliparae and the size of the subsequent study. DESIGN: a two part study: a pilot, RCT with follow-up through to delivery with postnatal maternal surveys, and a case review of nulliparae with dystocia. SETTING: a large maternity unit in the South of England in May-July 1997 inclusive. PARTICIPANTS: nulliparae with dystocia in the first stage of labour who had an otherwise uncomplicated obstetric background. INTERVENTIONS: women in the pilot RCT received one of three management options: labouring in a waterbirth pool, conservative management or augmentation of labour, which is the standard management of women with dystocia condition in the Unit. FINDINGS: it is feasible to conduct an RCT of management of dystocia in the Unit. Seventy per cent (95% confidence interval 47% to 87%) of women approached agreed to participate. Conservative management was the least acceptable option to women and has been dropped from the subsequent trial. The audit provided some idea of possible differences in operative delivery and epidural rates depending on augmentation or not. A sample of 220 women should be large enough to detect moderate changes and will require a 2-year recruitment period. CONCLUSIONS: a subsequent trial is feasible and is now underway. It has the potential to provide information enabling women and practitioners to have a greater choice of care options in the presence of dystocia, or provide a good basis for an even larger trial. PMID- 11207104 TI - Contemporary breast-feeding policy and practice: implications for midwives. AB - In this paper, the authors draw upon recent Australian research to provide a critical commentary on the current policies and professional practices surrounding breast feeding. These studies, conducted by the first and second authors, explored aspects of the breast-feeding experience, with the findings highlighting areas for concern in relation to the promotion and support of breast feeding in western societies. Of particular concern to the authors was the number of women in these studies who equated breastfeeding with being a 'good' mother. This perception meant that some women maintained a strong commitment to breast feeding despite enormous difficulties. In this paper we firstly, overview the findings of these studies and use women's stories to illustrate their perseverance and their intense commitment to breast feeding. In the second part of the paper, we consider the consequences of the strong public rhetoric surrounding breast feeding in Australia and challenge some of the assumptions underlying policies and professional practices related to breast feeding. We examine the consequences of 'professionalising' breast feeding, and make suggestions for a way forward in the promotion of breast feeding that encompasses the range of perspectives held by women. In conclusion, the authors highlight the complexity of establishing appropriate breast-feeding policies that guide professional practices in a flexible manner, allowing for diversity in individual breast-feeding experiences. PMID- 11207105 TI - The instruction in pelvic floor exercises provided to women during pregnancy or following delivery. AB - OBJECTIVES: to examine the instruction in pelvic floor exercises given to women during pregnancy or following delivery, to assess the quality of any instruction provided, and to consider these in light of the women's views about the service. DESIGN: a postal questionnaire was sent to a sample of women when they reached 34 weeks of pregnancy and a second at 8 weeks postpartum. A sub-sample of women who reported symptoms of stress incontinence at 8 weeks postpartum were interviewed about the instruction in pelvic floor exercises that they received during their pregnancy, or in the puerperium. PARTICIPANTS: of the 918 women who were sent the first questionnaire, 717 returned it completed (78%). Five-hundred-and-seventy two of 894 women (64%) completed the second questionnaire. Forty-two of 179 symptomatic women (23%) took part in an interview. FINDINGS: 55% of women received some form of instruction in pelvic floor exercises by 34 weeks of pregnancy. Eighty-six percent received instruction following birth. The way the information was given varied, ranging from a brief reminder, to exercising in a class with an instructor. The information was provided by a range of health professionals, and no single profession appeared to undertake responsibility for the service. As a result, the views of the service varied. A few women reported that they had received good quality instruction, others were critical of it, and a small number reported that they had received no instruction at all. The widespread practice of leaving a leaflet by the women's beds during their stay in hospital, was criticised by a large proportion of the women. KEY CONCLUSION: the instruction in pelvic floor exercises by health service professionals was provided on an ad hoc basis. In many instances, the programme of instruction did not meet recommendations made in the literature. It is likely that the success of randomised controlled trials reported in the literature would not be repeated in the 'real world' Implications for practice: there is a need for the service to be reorganised so that all women receive high-quality instruction during pregnancy, with a reminder to exercise following birth. This could help to prevent, or relieve, the symptoms of stress incontinence that frequently occur at these times. PMID- 11207106 TI - The process of implementing a community-based peer breast-feeding support programme: the Glasgow experience. AB - AIM: to document the process of implementing and maintaining a community-based peer-support programme. DESIGN AND SETTING: a community-based study located in a socio-economically disadvantaged housing estate on the outskirts of Glasgow. PARTICIPANTS: pregnant women residing in a target postcode area. INTERVENTION: a programme of peer counselling and support for breast feeding, comprising antenatal and postnatal home visits over a period of three years. IMPLICATIONS FOR PRACTICE: peer support may provide an acceptable and appropriate role model for breast-feeding mothers. However, further research is required on other influential factors such as the social network and the impact of this programme on the peer supporter. CONCLUSIONS: despite a low prevalence of breast feeding, initiating and maintaining peer breast-feeding support was possible. Peer support appeared to be acceptable to mothers and health professionals. Study mothers spoke enthusiastically of the intervention and mentioned increased confidence and self-esteem. PMID- 11207107 TI - The 'Term Breech Trial': findings of this major international study leave a question mark over midwives' role in breech delivery. PMID- 11207108 TI - Crithidia guilhermei: purification and partial characterization of a 62-kDa extracellular metalloproteinase. AB - An extracellular metalloproteinase from Crithidia guilhermei, a monoxenic trypanosomatid of insects, was purified 11-fold by ammonium sulfate precipitation, gel filtration on a Shinpack Diol-150 column, and anion-exchange chromatography in a MONO Q column, both using the HPLC system. The proteinase appeared as a single band with an apparent molecular mass of 62 kDa in SDS-PAGE, under reducing conditions, and was optimally active at 37 degrees C and pH 6.0. The enzyme showed 62% residual activity at 50 degrees C for 30 min. The proteinase was completely inhibited by 1, 10-phenanthroline, indicating that the enzyme belongs to the metalloproteinase class. This is the first report of the purification of an extracellular metalloproteinase from the Crithidia species. The possible role of this enzyme in the digestive tract of the insect host is discussed. PMID- 11207109 TI - Electron and video-light microscopy analysis of the in vitro effects of pyrantel pamoate on Giardia lamblia. AB - Electron and video-light microscopy analysis of the in vitro effects of pyrantel pamoate on Giardia lamblia. Experimental Parasitology 97, 9-14. Giardia infection is predominant in the small intestine of vertebrates, where the trophozoites attach to epithelial cells and adversely affect the microvilli and other epithelial cell structures. Giardiasis, the disease caused by this protozoan, is very common in developing countries and mainly affects children. Drugs currently used to treat Giardia infection, such as some benzimidazole derivatives, were originally designed to treat helminthic infections. Many of the drugs are known to cause severe side effects and disturbances to the patient. Using transmission electron microscopy and video-light microscopy, we studied the effects of pyrantel pamoate, a drug commonly used in the treatment of helminthic infections in horses and ruminants, on Giardia lamblia trophozoites. Pyrantel pamoate was administered to Giardia cells in four different concentrations. Using video-light microscopy, we observed the decrease in flagella beating frequency and severe changes in the lateral flange and in the general aspect of the cell. Using transmission electron microscopy, we observed changes in the cytoplasm and peripheral vesicles. The flagella and adhesive disk structure were not affected. Apparently, the effects of pyrantel pamoate are irreversible. PMID- 11207110 TI - Trypanosoma cruzi: peripheral blood monocytes and heart macrophages in the resistance to acute experimental infection in rats. AB - The contribution of mononuclear phagocytes to host resistance against acute Chagas disease has been studied in vivo in a rat model inoculated with Trypanosoma cruzi, Y strain. Acute T. cruzi infection triggered a dramatic increase (937%) in peripheral blood monocyte number at day 12 of infection. At this point, histological analysis of the heart showed high parasitism and diffuse and a moderate to intense mononuclear inflammatory process. Ultrastructural study revealed a large number of macrophages, in addition to lymphocytes and undiffer entiated cells. Clusters of macrophages exhibited different morphologi cal phenotypes, with evident signs of activation (increase in size, surface rufflings, and amount of cytoplasmic organelles). Cell-to-cell contacts involving macrophages and lymphocytes or macrophages and mono cytes were observed. Depletion of macrophages by treatment with silica, a selective cytotoxic agent for these cells, caused a significant increase in the number of amastigote nests in cardiomyocytes. The present findings indicate that the early phase of infection with T. cruzi induces rapid production, maturation, and activation of the monocyte/macrophage system so as to control T. cruzi replication, emphasizing the crucial role for macrophages in the rat resistance to Chagas disease. PMID- 11207111 TI - Onchocerca volvulus: genetic diversity of parasite isolates from Sudan. AB - Onchocerciasis in Sudan exists in three distinct foci which exhibit differing clinical presentations. Previous studies have demonstrated that a tandemly repeated Onchocerca sequence family with a unit repeat length of 150 bp (the O 150 family) is a useful marker for deducing relationships among different O. volvulus populations. In the current study, the O-150 repeat families of O. volvulus from Sudan were analyzed and compared to each other and to those of parasites from West Africa. Similar to West African and American O. volvulus, the O-150 families of the Sudanese parasites could be divided into clusters within which little or no intracluster variation was evident, suggesting that the O-150 family in these parasites was subject to the forces of concerted evolution. Statistical analysis of the O-150 families from the different Sudanese parasite isolates, employing a nested algorithm based on an analysis of variance, revealed that O. volvulus endemic to the northern focus at Abu Hamed were significantly different from all other O. volvulus populations examined to date. In contrast, parasites from the southern and eastern foci of Sudan were indistinguishable from those endemic to the West African savanna. The significance of these data are discussed in light of knowledge of the biogeography and biology of transmission of O. volvulus in Africa. PMID- 11207112 TI - Leishmania donovani: intraspecific polymorphisms of Sudanese isolates revealed by PCR-based analyses and DNA sequencing. AB - Four polymerase chain reaction (PCR)-based approaches were used to analyze diversity within 23 Sudanese isolates of Leishmania donovani. Methods compared were fingerprinting with single nonspecific primers, restriction analysis of the amplified ribosomal internal transcribed spacer (ITS) locus, single-stranded conformation polymorphism (SSCP), and sequencing of the ITS region. When PCR fingerprinting and restriction analysis of ITS were applied, highly similar fragment patterns were observed for all strains of L. donovani studied. The ITS1 locus gave five different SSCP profiles among the 23 Sudanese isolates, whereas the ITS2 locus was highly conserved with the exception of 1 isolate. Strains of L. donovani derived from other geographical areas were found to have different ITS2 patterns. SSCP analysis correlated well with results of DNA sequencing and confirmed that SSCP was able to detect genetic diversity at the level of a single nucleotide. SSCP had advantages over the other methods employed for investigation of sequence variation within the species L. donovani. There was no correlation between the form of clinical manifestation of the disease and the PCR fingerprinting, ITS-RFLP, or ITS-SSCP characteristics. PMID- 11207113 TI - Plasmodium falciparum: production and characterization of rat monoclonal antibodies specific for the sexual-stage Pfs48/45 antigen. PMID- 11207114 TI - Long PCR amplification of Plasmodium falciparum DNA extracted from filter paper blots. PMID- 11207115 TI - Isolation and characterization of a cold-sensitive attachment/invasion mutant of Toxoplasma gondii. PMID- 11207116 TI - A new technique for the repair and reconstruction of frontoethmoidal encephalomeningoceles by medial orbital composite-unit translocation. AB - A frontoethmoidal encephalomeningocele is a herniation of brain and meninges through a congenital bone defect in the skull at the junction of the frontal and ethmoidal bones. Between 1992 and 1999, we treated 145 cases of frontoethmoidal encephalomeningocele. Before 1993, the operation was performed in two stages. An intracranial repair by neurosurgeons preceded the external extirpation of the mass. In 70 cases that were operated on after 1993, a one-stage closure of the skull defect with a medial orbital composite-unit translocation technique was used. The medial orbital rim on each side, with intact periosteum, medial canthal ligament and lacrimal apparatus, was translocated as a unit to the midline. The advantages of this technique are that it allows convenient access to resect the herniation mass and close the defect, it restores normal interorbital and intercanthal distances and it eliminates the need for a transnasal medial canthopexy. Augmentation rhinoplasty can be avoided in most cases by tilting the composite unit with its preserved blood supply. PMID- 11207117 TI - The panda naevus: management of synchronous upper- and lower-eyelid pigmented naevi. AB - We report four patients presenting with rare synchronous upper- and lower-eyelid naevi. The distributions and appearances of these naevi resemble the distinctive periorbital pigmentation of the panda. The possible embryological origin of this naevus and an approach to management are discussed. PMID- 11207118 TI - Eyelid reconstruction using a hard palate mucoperiosteal graft combined with a V Y subcutaneously pedicled flap. AB - Full-thickness eyelid defects after tumour ablation require the reconstruction of two layers, the anterior and posterior lamellae. Eyelids were successfully reconstructed after removal of malignant tumours in four patients using a hard palate mucoperiosteal graft combined with a curved V-Y subcutaneously pedicled flap. Although there have been some reports of hard palate mucosal grafts for reconstruction of the posterior lamella, the graft is not sufficiently rigid to support the reconstructed eyelid without the aid of supporting materials such as cartilage grafts. The hard palate mucoperiosteal graft seems to be rigid enough to support the reconstructed eyelid without the use of cartilage or other supporting materials. The subcutaneously pedicled V-Y advancement flap is useful for reconstruction of the anterior lamella in partial eyelid defects. We used it with a modified curved design to allow easy advancement and to make postoperative scars inconspicuous. PMID- 11207119 TI - Pre-arterialisation of an arterialised venous flap: clinical cases. AB - Many factors affecting the survival of arterialised venous flaps have been elucidated, both experimentally and clinically. The survival of large arterialised venous flaps has been reported, with varying results. Large arterialised venous flaps with preformed arteriovenous fistulae at the donor sites have been successfully performed in experimental animals. We report the results of repair of skin defects in the extremities with arterialised venous flaps in eight patients. The arteriovenous shunts were created at the donor sites at least 2 weeks before the flaps were harvested. The flap sizes ranged between 4 x 4cm and 9 x 10 cm. Flap survival was between 93% and 100% of the surface area, as shown by digitalised scanning. In addition to the known advantages of venous flaps, such as less bulk, preservation of the main arteries and ease of harvesting, pre-arterialisation makes designing the flap easier due to the noticeable superficial veins. Pre-arterialisation, when used in carefully selected cases, did not prolong the hospital course of the patients. PMID- 11207120 TI - Correction of pectus excavatum using a sternal elevator: preliminary report. AB - Operative procedures to correct the deformity caused by pectus excavatum are generally based on either sternal elevation or turnover. In either case, the operation is highly invasive. By considering the softness of the costal cartilages in early childhood, we have developed an endoscopically assisted procedure that applies external traction continuously in order to elevate the depressed sternum and costal cartilages. Since August 1993, we have performed this operation in 11 patients with pectus excavatum who ranged in age from 3 years 1 month to 28 years. The traction screws came loose spontaneously in two early cases. Augmentation transfer of a latissimus dorsi muscle flap and dermal fat grafting were subsequently performed in these two patients, respectively. We achieved an excellent cosmetic outcome in the other nine patients, with results similar to those achieved with the conventional operation. Our technique is a two stage procedure and the patient is limited in performing daily activities while wearing the traction device. Despite this drawback it can achieve permanent correction of the deformity. Accordingly, this method should be considered when pectus excavatum is corrected surgically, particularly in infants and young children. PMID- 11207121 TI - Trilucent breast implants: a 3 year series. AB - The use of Trilucent breast implants in the UK dates back to 1995 and their introduction coincided with the medium-term effects of the silicone-implant controversy. We present a review of 3 years' experience of the Trilucent implant (1996-1998) during which 29 patients with a mean age of 39.4 years had a total of 50 implants. The aim of the study was to analyse the results in these patients in terms of complications, reoperation rate and patient satisfaction. Using a combination of retrospective chart analysis and postal survey, we found an incidence of implant deflation of 10% (5/50). The overall reoperation rate was 20% (10/50). The postal survey yielded a mean satisfaction score of 7.1 (on a scale of 0-10) from the 20 respondents out of the 29 patients (68.9%). In view of the high complication rate, we discontinued the use of Trilucent implants in advance of their withdrawal by the Medical Devices Agency (MDA) in March 1999. However, these findings may now be considered of added interest, particularly with regard to patients who are opting to keep their Trilucent implants despite the recommendation of the MDA in June 2000 that such implants should be removed. PMID- 11207122 TI - Single axillary incision for quadrantectomy, axillary clearance and immediate reconstruction with latissimus dorsi. AB - This paper describes a method of immediate breast reconstruction following conservative breast surgery. The technique is innovative in that axillary clearance, quadrantectomy and the harvest of the latissimus dorsi muscle are carried out through a small transverse axillary incision with no incision in the breast. PMID- 11207123 TI - Classification of hand anomalies in Poland's syndrome. AB - Poland's syndrome classically consists of the combination of unilateral aplasia of the sternocostal head of the pectoralis major muscle and an ipsilateral hypoplastic hand with simple syndactyly and short fingers. However, patients with Poland's syndrome may have a broad range of hand anomalies. In this paper, the author reviews 20 cases of Poland's syndrome and offers a classification of the hand anomalies. The hand anomalies are divided into seven types according to the severity of the deformity. Clinical cases are presented along with similar cases from the literature. The aetiology of Poland's syndrome is discussed and the various malformations that may co-exist with this syndrome are reviewed. PMID- 11207124 TI - The effect of elevation on digital blood pressure. AB - Elevation of the hand is recommended for all patients undergoing hand surgery to decrease the swelling in the hand. This study was designed to look at the effects of elevation of the hand on digital blood pressure at different elevation positions. Digital blood pressure was recorded using a digital plethysmograph in 30 subjects for increasing levels of elevation above the heart. Friedman's test was applied to the blood-pressure changes recorded in the four positions of the upper limb and showed a significant sustained fall in mean blood pressure with increasing elevation, bringing into question the use of elevation in certain clinical situations. PMID- 11207125 TI - An evaluation of Polaroid photographic imaging for cutaneous-lesion referrals to an outpatient clinic: a pilot study. AB - A pilot study consisted of 65 patient referrals to a Regional Plastic Surgery Department in which the referral letter, accompanied by a high-quality Polaroid photograph, was assessed by four consultants. The diagnosis, degree of urgency of treatment, grade of surgeon (to undertake the operation) and anticipated time for the procedure were recorded. The results were statistically analysed. Our aim was to evaluate the diagnostic accuracy and consistency of the four observers. The majority of malignant skin lesions were detected accurately; those that were missed received urgent attention due to a high degree of suspicion. This study supports the view that 'triage' of referrals using high-quality photographic images in association with an accurate referral letter can offer a significant reduction in pressure on waiting time and inconvenience for patients by avoiding an additional outpatient visit. Advantages to purchasers in terms of cost savings on outpatient visits and travelling reimbursement can result from this initiative. PMID- 11207126 TI - Successful reduction in skin damage resulting from exposure to the normal-mode ruby laser in an animal model. AB - Normal-mode ruby laser (NMRL) irradiation of skin has now become an acceptable method of producing depilation. However, side effects, which include superficial burning and changes in skin pigmentation, still occur and, although temporary, can be distressing to the patient. This paper reports a method by which the skin can be protected (or preconditioned) from damage during NMRL treatment by pre heating to a lower, non-damaging level prior to irradiation. Using the black haired mouse (C57B1/10) as an animal model, an appropriate 'preconditioning' temperature was established by exposing the mouse skin to a range of temperatures, taking biopsies and staining the skin immunohistochemically for heat shock protein 70 (HSP 70) expression within the keratinocyte cells. Increased HSP 70 expression is stimulated by exposure to environmental stressors such as heat, so it was hypothesised that its increased expression conveyed increased cellular protection. The appropriate temperature (45 degrees C for 15 min) allowed for the superficial skin cells to be protected (as assessed by maximal HSP 70 staining) but undamaged (as assessed by haematoxylin and eosin staining), leaving the target hair-producing cells unprotected. Eight mice (16 flanks) were then exposed to this preconditioning temperature (eight of the flanks being growing-hair sites and eight resting-hair sites) and 5 h later exposed to a laser fluence known to cause mild skin damage and depilation (6J/cm2). This exposure was to both the preconditioned and the adjacent non preconditioned sites. A statistically significant reduction in skin damage (P <0.001), as measured by the time taken to heal and noted both clinically and histologically, was seen in the preconditioned sites in resting-hair regions but not in growing-hair regions. Depilation, established over an 8 week period, was successful in growing-hair regions within both preconditioned and non preconditioned sites, but complete hair regrowth had occurred in preconditioned and non-preconditioned sites within resting-hair regions by 5 weeks. The latter finding was consistent with work already reported suggesting that NMRL-assisted depilation in this animal model is not successful for hairs in the telogen phase. Successful preconditioning of mouse skin prior to laser exposure appears to reduce NMRL-induced skin side effects. In addition, the technique does not appear to adversely affect successful depilation. PMID- 11207127 TI - Do superficial epigastric veins of rats have valves? AB - The rat is a good model for experimental studies on the haemodynamic patterns of free-flap transfer but models involving the superficial epigastric vein have not been supported by the demonstration of the anatomical presence or absence of valves inside it. We performed a morphological study to assess whether or not valves are present inside the superficial epigastric vein of the rat. Segments of superficial epigastric veins were explanted from fifteen Sprague-Dawley rats. The lumen was studied with scanning electron microscopy after longitudinal or transverse incision of the venous walls. No valves were detected and we saw no evidence of their accidental removal. As most human veins do have valves, the clinical implications of haemodynamic data on reverse-flow island flaps obtained in rats must be considered very carefully. PMID- 11207128 TI - Basal cell carcinomata in port wine stains. AB - The development of basal cell carcinoma (BCC) in a port wine stain is rare and the aetiology of these malignancies in this situation is the subject of some debate. Early treatment of port wine stains with ionising radiation has been implicated in the development of BCC. The use of the argon laser has not been implicated. We present four cases of BCC in port wine stains, one previously treated with an argon laser, and discuss the possible aetiological factors. PMID- 11207129 TI - Moustache reconstruction using an extended midline forehead flap. AB - A new method for reconstruction of the upper lip and moustache is presented. An extended midline forehead flap is described, which is a modification of the classical midline forehead flap in which the flap is extended into the hair bearing scalp. Simultaneously, a nasal alar defect was reconstructed using the non-hair-bearing forehead skin in a patient with cancrum oris. The flap is reliable, technically easy to raise, does not require any special expertise and causes minimal donor site deformity. However, it is a multistage procedure and hence causes prolonged morbidity. PMID- 11207130 TI - Isolated bilateral orbital neurofibromatosis in a twelve-year-old. AB - A patient with bilateral orbital neurofibromatosis is described. This patient had no other dysmorphic features and no systemic stigmata indicative of Von Recklinghausen's disease or endocrine syndromes. To our knowledge, this is the first report in the literature of isolated bilateral orbital neurofibromatosis in an otherwise normal patient. PMID- 11207131 TI - External venous shunt as a solution to venous thrombosis in microvascular surgery. AB - We report a case in which venous occlusion occurred after fibular osteocutaneous flap transfer for open tibial fracture. The flap was salvaged using an external venous shunt. The shunt consisted of a Teflon catheter for intravenous infusion, a three-way stopcock, a urokinase-immobilised catheter and a pressurising bag for arterial-pressure monitoring. This method can be used to establish venous drainage when there is no accessible recipient vein. It may improve the success rate of microvascular surgery and extend the indications for surgery. PMID- 11207132 TI - Avulsion of vascular anastomosis in free-flap breast reconstruction. AB - We report a case of anastomotic avulsion following a free deep inferior epigastric perforator (DIEP) flap reconstruction immediately after mastectomy for carcinoma of the breast. This occurred on the 5th postoperative day when the patient was allowed a shower and abducted her shoulders to wash her hair. The aim of this report is to make readers aware of such a possibility, and we suggest exercising caution in early mobilisation of the upper limb after free-flap breast reconstruction. PMID- 11207133 TI - Cutaneous verrucous carcinoma. AB - Verrucous carcinoma is a rare, low-grade, well-differentiated squamous cell carcinoma most commonly seen on mucosa. It has been infrequently reported to occur on the skin, where it is a slow-growing and locally aggressive tumour. It is not uncommon for cutaneous verrucous carcinomas to be mistaken for the more frequent verruca vulgaris and treated accordingly. Three cases of cutaneous verrucous carcinoma are presented with the medical history and follow-up data. Surgery is the treatment of choice; these lesions may sustain a potentially anaplastic transformation after radiation therapy. PMID- 11207134 TI - Distal plantar area reconstruction using a flexor digitorum brevis muscle flap with reverse-flow lateral plantar artery. AB - It is difficult to resurface skin defects of the sole because of its unique anatomy, which is resistant to mechanical stimuli. Though various methods have been reported, few are functionally satisfactory, and it is especially difficult to repair the distal plantar area. We report a reconstruction of the distal plantar area using a flexor digitorum brevis muscle flap based on a reverse-flow lateral plantar artery pedicle in a patient with a malignant melanoma on the right lateral metatarsal head of the fifth toe. The muscle flap was sufficient to cover the exposed fifth metatarsal and was covered with a full-thickness skin graft. The result was favourable and the patient has a normal gait and no pressure sores. PMID- 11207135 TI - Pedicled scrotal island skin flap in the treatment of anal basal cell carcinoma. AB - Basal cell carcinoma of the anus is extremely rare, accounting for only 0.1% of anorectal malignancies. We report the reconstruction of the anus with a biaxial pedicled scrotal island myofasciocutaneous flap following excision of an anal basal cell carcinoma, and conclude that this technique may be valuable in the reconstruction of the anal region. PMID- 11207136 TI - Subungual pilonidal sinus of the hand in a dog groomer. AB - Interdigital pilonidal sinus of the hand is an occupational hazard in barbers, sheep shearers and cow milkers. We present a case of a subungual pilonidal sinus of the thumb of a dog groomer, complicated by the development of osteomyelitis in the distal phalanx. PMID- 11207137 TI - Paraffinoma--a complication of Jelonet packs following rhinoplasty. PMID- 11207138 TI - Best use of anomaly of radial artery. PMID- 11207139 TI - A dermoid cyst presenting as an epidermoid cyst in the malar region. PMID- 11207140 TI - Ametop gel and suture removal. PMID- 11207142 TI - New use for a prep sponge. PMID- 11207141 TI - Mycobacterium marinum hand infection. PMID- 11207143 TI - A novel method of ring removal from a swollen finger. PMID- 11207144 TI - Free TRAM flap breast reconstruction: V-flap to improve vessel access. PMID- 11207145 TI - Incidence of incomplete excision in surgically treated basal cell carcinoma: a retrospective clinical audit. PMID- 11207147 TI - Invited commentary: studies of workers exposed to low doses of radiation. PMID- 11207146 TI - First analysis of cancer incidence and occupational radiation exposure based on the National Dose Registry of Canada. AB - A cohort study was conducted to investigate the relation between cancer incidence and occupational exposure to ionizing radiation. Records containing dose information from 1951 to 1988 for 191,333 persons were extracted from the National Dose Registry of Canada. The records were linked to the Canadian Cancer Data Base, with incidence data from 1969 to 1988. Standardized incidence ratios were calculated using Canadian cancer incidence rates stratified by age, sex, and calendar year. Excess relative risks were obtained from internally based dose response analyses. The following significant results were found for males and females combined: a deficit in the standardized incidence ratio for all cancers combined; elevated standardized incidence ratios for thyroid cancer and melanoma; and elevated excess relative risks for rectum, leukemia, lung, all cancers combined, all except lung, and all except leukemia. For males, cancers of the colon, pancreas, and testis also showed significantly elevated excess relative risks. The specific cancer types listed above have been implicated in previous studies on occupational exposure to ionizing radiation, except for testis, colon, and melanoma, while the findings on thyroid cancer from previous studies are inconclusive. The thyroid standardized incidence ratios in this study are highly significant, but further investigation is needed to assess the possibility of association with occupational radiation exposure. PMID- 11207148 TI - Sont et al. Respond to "Studies of Workers Exposed to Low Doses of Radiation" PMID- 11207149 TI - Maternal exposure to nitrate from drinking water and diet and risk for neural tube defects. AB - In this population-based case-control study conducted in California between June 1989 and May 1991, the authors investigated the association between maternal periconceptional exposure to nitrate from drinking water and diet and risk for neural tube defects. The mothers of 538 cases and 539 nonmalformed controls were interviewed regarding residential history, consumption of tap water at home, and dietary intake during the periconceptional period. Dietary nitrate exposure was not associated with increased risk for neural tube defects. Exposure to nitrate in drinking water at concentrations above the 45 mg/liter maximum contaminant level was associated with increased risk for anencephaly (odds ratio (OR) = 4.0, 95% confidence interval (CI): 1.0, 15.4), but not for spina bifida. Increased risks for anencephaly were observed at nitrate levels below the maximum contaminant level among groundwater drinkers only (OR = 2.1, 95% CI: 1.1,4.1 for 5-15 mg/liter; OR = 2.3, 95% CI: 1.1, 4.5 for 16-35 mg/liter; and OR = 6.9, 95% CI: 1.9, 24.9 for 36-67 mg/liter compared with <5 mg/liter). Adjustment for identified risk factors for anencephaly did not substantially alter these associations, nor did control for maternal dietary nitrate, total vitamin C intake, and quantity of tap water consumed. The lack of an observed elevation in risk for anencephaly in association with exposure to mixed water containing nitrate at levels comparable with the concentration in groundwater may indicate that something other than nitrate accounts for these findings. PMID- 11207150 TI - Placental abruption and perinatal mortality in the United States. AB - Placental abruption is an uncommon obstetric complication associated with high perinatal mortality rates. The authors explored the associations of abruption with fetal growth restriction, preterm delivery, and perinatal survival. The study was based on 7,508,655 singleton births delivered in 1995 and 1996 in the United States. Abruption was recorded in 6.5 per 1,000 births. Perinatal mortality was 119 per 1,000 births with abruption compared with 8.2 per 1,000 among all other births. The high mortality with abruption was due, in part, to its strong association with preterm delivery; 55% of the excess perinatal deaths with abruption were due to early delivery. Furthermore, babies in the lowest centile of weight (<1% adjusted for gestational age) were almost nine times as likely to be born with abruption than those in the heaviest (> or =90%) birth weight centiles. This relative risk progressively declined with higher birth weight centiles. After controlling for fetal growth restriction and early delivery, the high risk of perinatal death associated with abruption persisted. Even babies born at 40 weeks of gestation and birth weight of 3,500-3,999 g (where mortality was lowest) had a 25-fold higher mortality with abruption. The link between fetal growth restriction and abruption suggests that the origins of abruption lie at least in midpregnancy and perhaps even earlier. PMID- 11207151 TI - Fingerprint ridge-count difference between adjacent fingertips (dR45) predicts upper-body tissue distribution: evidence for early gestational programming. AB - Fingerprint ridge counts, which remain constant from the 19th week of pregnancy, are related to fingertip growth during early gestation. Each finger corresponds neurologically to a spinal-cord segment ranging from C6 (thumb, relatively cephalad) to C8 (fifth finger, relatively caudad). The authors hypothesized that large ridge-count differences between fingertips (cephalad > caudad) might reflect fetal inhibition of caudal growth. Among 69 male Atlanta, Georgia, military recruits (1994-1997; aged 17-22 years), they tested associations of the anthropometric waist-to-thigh ratio with 20 ridge-count differences. Waist-to thigh ratio was associated with the ridge-count difference between the right fourth and fifth fingertips only (dR45; r = 0.36, p = 0.003). The race-adjusted standardized regression coefficient was 0.22 (95% confidence interval: 0.03, 0.41). Since upper-body tissue distribution indicates disease risk, the authors then tested the association of age (an indicator of survivorship) with dR45 in a sample of 135 male patients from Bangalore, India (1989-1990; aged 38-82 years). Age was inversely associated with dR45 (r = -0.17, p = 0.04), notably among the 75 men with diabetes (r = -0.22, p = 0.06). An increased dR45 predicts an upper body tissue distribution originating before the midpoint of pregnancy. The cause of this developmental pattern is unknown, but it may lead to reduced survivorship. PMID- 11207152 TI - Predictive 5-year survivorship model of cystic fibrosis. AB - The objective of this study was to create a 5-year survivorship model to identify key clinical features of cystic fibrosis. Such a model could help researchers and clinicians to evaluate therapies, improve the design of prospective studies, monitor practice patterns, counsel individual patients, and determine the best candidates for lung transplantation. The authors used information from the Cystic Fibrosis Foundation Patient Registry (CFFPR), which has collected longitudinal data on approximately 90% of cystic fibrosis patients diagnosed in the United States since 1986. They developed multivariate logistic regression models by using data on 5,820 patients randomly selected from 11,630 in the CFFPR in 1993. Models were tested for goodness of fit and were validated for the remaining 5,810 patients for 1993. The validated 5-year survivorship model included age, forced expiratory volume in 1 second as a percentage of predicted normal, gender, weight for-age z score, pancreatic sufficiency, diabetes mellitus, Staphylococcus aureus infection, Burkerholderia cepacia infection, and annual number of acute pulmonary exacerbations. The model provides insights into the complex nature of cystic fibrosis and supplies a rigorous tool for clinical practice and research. PMID- 11207153 TI - Coffee consumption and serum lipids: a meta-analysis of randomized controlled clinical trials. AB - Coffee drinking has been associated with increased serum cholesterol levels in some, but not all, studies. A Medline search of the English-language literature published prior to December 1998, a bibliography review, and consultations with experts were performed to identify 14 published trials of coffee consumption. Information was abstracted independently by two reviewers using a standardized protocol. With a random-effects model, treatment effects were estimated by pooling results from individual trials after weighting the results by the inverse of total variance. A dose-response relation between coffee consumption and both total cholesterol and LDL cholesterol was identified (p < 0.01). Increases in serum lipids were greater in studies of patients with hyperlipidemia and in trials of caffeinated or boiled coffee. Trials using filtered coffee demonstrated very little increase in serum cholesterol. Consumption of unfiltered, but not filtered, coffee increases serum levels of total and LDL cholesterol. PMID- 11207154 TI - Neighborhood socioeconomic status and all-cause mortality. AB - This study sought to determine the contribution of neighborhood socioeconomic status to all-cause mortality and to explore its correlates. As part of the longitudinal "Gezondheid en LevensOmstandigheden Bevolking en omstreken" (GLOBE) study in the Netherlands, 8,506 randomly selected men and women aged 15-74 years from 86 neighborhoods in the city of Eindhoven reported on their socioeconomic status in the 1991 baseline survey. During the 6-year follow-up, 487 persons died. Neighborhood socioeconomic status was derived from individual reports on socioeconomic status. Its effect on mortality was stringently controlled for four individual-level socioeconomic indicators. Persons living in a neighborhood with a high percentage of unemployed/disabled or poor persons had a higher mortality risk than did those living in a neighborhood with a low percentage of unemployed/disabled or poor persons. This was independent of individual socioeconomic characteristics, including individual unemployment/disability or reports of severe financial problems. Educational and occupational neighborhood indicators were similarly, but less strongly, related to mortality. The prevalence of poor housing conditions, social disintegration, and unhealthy psychologic profiles and behaviors was higher in neighborhoods with a low socioeconomic status. Contextual effects of socioeconomic status may thus be due to one or more of these specific circumstances. The findings indicate potential public health benefits of modifying socioeconomic characteristics of areas. PMID- 11207155 TI - Immigration and the health of Asian and Pacific Islander adults in the United States. AB - The authors used the 1992-1995 National Health Interview Survey to examine the effect of immigrant status (both nativity and duration of residence in the United States) on the health of Asian and Pacific Islander adults by constructing models in which national origin was also specified. In logistic regression models adjusted for age, marital status, living arrangement, family size, and several socioeconomic indicators, immigrants were found to be in better health than their US-born counterparts, but their health advantages consistently decreased with duration of residence. For example, for Asian and Pacific Islander immigrants whose duration of residence was less than 5 years, 5-9 years, and 10 years or more, the odds ratios for activity limitations were 0.45 (95% confidence interval (CI): 0.33, 0.62), 0.65 (95% CI: 0.46, 0.93), and 0.73 (95% CI: 0.60, 0.90), respectively. Similar findings emerged for respondent-reported health and bed days due to illness. These results support the validity and complementarity of the migration selectivity and acculturation hypotheses. However, the picture was not uniformly positive. The health of certain Asian and Pacific Islander groups, notably Pacific Islanders and Vietnamese, was found to be less favorable than average. Finally, after adjustment for health status, immigrants seemed to have less adequate access to formal medical care. PMID- 11207156 TI - Early therapy for latent tuberculosis infection. AB - The risk of developing active tuberculosis is highest within the first 2 years of infection. Therefore, an intervention that targets persons with recent infection, such as identifying contacts of active cases, could be particularly effective as an epidemic control measure. A mathematical model of a tuberculosis epidemic is formulated and used to evaluate the strategy of targeting therapy to persons with recently acquired latent tuberculosis infection. The model is used to quantify the effectiveness of therapy for early latent tuberculosis infection in reducing the prevalence of active tuberculosis. The model is also used to demonstrate how effective therapy for early latent tuberculosis infection has to be to eliminate tuberculosis, when used in conjunction with therapy for active tuberculosis. Analysis of the model suggests that programs such as contact investigations, which identify and treat persons recently infected with Mycobacterium tuberculosis, may have a substantial effect on controlling tuberculosis epidemics. PMID- 11207157 TI - Modeling changes in CD4-positive T-lymphocyte counts after the start of highly active antiretroviral therapy and the relation with risk of opportunistic infections: the Aquitaine Cohort, 1996-1997. AB - After initiation of a treatment for human immunodeficiency virus type 1 infection containing a protease inhibitor, immune restoration associated with increases in CD4-positive (CD4+) T lymphocyte count may be delayed. In a sample of patients who had been prescribed protease inhibitors for the first time, the authors tested to see whether there was a minimal duration of CD4+ cell count increase before the increase had an impact on the occurrence of opportunistic infections. The evolution (difference between time t and baseline) of CD4+ cell count was modeled using a mixed effects linear model. Changes in CD4+ count estimated by this model were then included as time-dependent covariates in a proportional hazards model. Finally, the authors tested for the existence of a CD4+ change x time interaction. The authors used a sample of 553 French patients first prescribed protease inhibitors in 1996 and followed for a median of 16 months. During the first 120 days, there was no association between CD4+ change and the rate of opportunistic infections. After 120 days, each 50-cell/mm3 increase in CD4+ count was associated with a 60% (95% confidence interval: 45, 72) reduction in the incidence of opportunistic infections. These results, based on modeling of CD4+ cell response, at least indirectly reinforce the concept of a delayed but possible immune recovery with the use of protease inhibitors. The findings support the potential for interruption of certain types of prophylaxis against opportunistic infections under reasonable conditions of duration of antiretroviral therapy and sustained CD4+ cell response. PMID- 11207158 TI - Empirical evidence of correlated biases in dietary assessment instruments and its implications. AB - Multiple-day food records or 24-hour recalls are currently used as "reference" instruments to calibrate food frequency questionnaires (FFQs) and to adjust findings from nutritional epidemiologic studies for measurement error. The common adjustment is based on the critical requirements that errors in the reference instrument be independent of those in the FFQ and of true intake. When data on urinary nitrogen level, a valid reference biomarker for nitrogen intake, are used, evidence suggests that a dietary report reference instrument does not meet these requirements. In this paper, the authors introduce a new model that includes, for both the FFQ and the dietary report reference instrument, group specific biases related to true intake and correlated person-specific biases. Data were obtained from a dietary assessment validation study carried out among 160 women at the Dunn Clinical Nutrition Center, Cambridge, United Kingdom, in 1988-1990. Using the biomarker measurements and dietary report measurements from this study, the authors compare the new model with alternative measurement error models proposed in the literature and demonstrate that it provides the best fit to the data. The new model suggests that, for these data, measurement error in the FFQ could lead to a 51% greater attenuation of true nutrient effect and the need for a 2.3 times larger study than would be estimated by the standard approach. The implications of the results for the ability of FFQ-based epidemiologic studies to detect important diet-disease associations are discussed. PMID- 11207159 TI - Is shorter always better? Relative importance of questionnaire length and cognitive ease on response rates and data quality for two dietary questionnaires. AB - In this study, the authors sought to determine the effects of length and clarity on response rates and data quality for two food frequency questionnaires (FFQs): the newly developed 36-page Diet History Questionnaire (DHQ), designed to be cognitively easier for respondents, and a 16-page FFQ developed earlier for the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The PLCO Trial is a 23-year randomized controlled clinical trial begun in 1992. The sample for this substudy, which was conducted from January to April of 1998, consisted of 900 control and 450 screened PLCO participants aged 55-74 years. Controls received either the DHQ or the PLCO FFQ by mail. Screenees, who had previously completed the PLCO FFQ at baseline, were administered the DHQ. Among controls, the response rate for both FFQs was 82%. Average amounts of time needed by controls to complete the DHQ and the PLCO FFQ were 68 minutes and 39 minutes, respectively. Percentages of missing or uninterpretable responses were similar between instruments for questions on frequency of intake but were approximately 3 and 9 percentage points lower (p < or = 0.001) in the DHQ for questions on portion size and use of vitamin/mineral supplements, respectively. Among screenees, response rates for the DHQ and the PLCO FFQ were 84% and 89%, respectively, and analyses of questions on portion size and supplement use showed few differences. These data indicated that the shorter FFQ was not better from the perspective of response rate and data quality, and that clarity and ease of administration may compensate for questionnaire length. PMID- 11207160 TI - Chronic musculoskeletal and other idiopathic pain syndromes. PMID- 11207162 TI - Stamps in paediatrics: Oral rehydration therapy. PMID- 11207161 TI - Incidence, aetiology, and outcome of non-traumatic coma: a population based study. AB - AIM: To determine the incidence, presentation, aetiology, and outcome of non traumatic coma in children aged between 1 month and 16 years. METHODS: In this prospective, population based, epidemiological study in the former Northern NHS region of the UK, cases were notified following any hospital admission or community death associated with non-traumatic coma. Coma was defined as a Glasgow Coma Score below 12 for more than six hours. RESULTS: The incidence of non traumatic coma was 30.8 per 100 000 children under 16 per year (6.0 per 100 000 general population per year). The age specific incidence was notably higher in the first year of life (160 per 100 000 children per year). CNS specific presentations became commoner with increasing age. In infants, nearly two thirds of presentations were with non-specific, systemic signs. Infection was the commonest overall aetiology. Aetiology remained unknown in 14% despite extensive investigation and/or autopsy. Mortality was highly dependent on aetiology, with aetiology specific mortality rates varying from 3% to 84%. With follow up to approximately 12 months, overall series mortality was 46%. PMID- 11207163 TI - Cognitive and adaptive outcomes and age at insult effects after non-traumatic coma. AB - Cognitive and adaptive behavioural outcome were studied in the identified survivors of a population based study of non-traumatic coma (NTC) in childhood. Children were assessed early (six weeks) and late (12 months) after NTC. At least 7% of those children in whom no suspicions of prior neurodevelopmental morbidity existed showed moderate or severe disability following NTC. Children over 2 years of age at insult showed some improvement between early and late assessments; however, children below 2 years showed no improvement. Differing age at insult effects were observed between aetiological groups. A relation between early age at first insult and poor outcome was particularly evident among children experiencing NTC caused by epilepsy. PMID- 11207164 TI - A review of measures of quality of life for children with chronic illness. AB - AIMS: To identify currently available generic and disease specific measures of quality of life (QoL) for work with children; and make recommendations about the future development and application of QoL measures. METHODS: Systematic searches were conducted to identify measures of QoL. Primary research papers were coded by the authors on the basis of predefined inclusion and exclusion criteria. RESULTS: Of the 137 papers included in the review, 43 involved the development of a new measure. These included 19 generic and 24 disease specific measures. Almost half the measures were developed in the USA. Measures were identified which were appropriate for children across a broad age range, and included provision for completion by different respondents (child only, parent only, or both). There were no clear distinctions between measures of QoL, health, or functional status. CONCLUSIONS: We have identified a small number of measures which fulfil basic requirements and could be used to assess QoL in clinical trials or following interventions. However, there remain a number of problems in measuring QoL in children. These include limited availability of disease specific measures; discrepancies between child and parent ratings; limited availability of measures for self completion by children; lack of precision regarding the content of domains of QoL; and the cultural appropriateness of measures developed elsewhere for children in the UK. PMID- 11207167 TI - Social class difference in catch up growth in a national British cohort. AB - AIM: To examine the influence of socioeconomic status on growth pattern in height from age 7 to 23 years. METHODS: Prospective cohort study. A total of 10 200 white singleton born children from the 1958 British birth cohort (National Child Development Study) were analysed. RESULTS: Differences in height by birth weight persisted throughout the follow up period. However, the mean differences in height between low birth weight infants (<2500 g) and adequate birth weight infants (>/=2500 g) were less notable in social classes I and II than in the lower social classes. The catching up of growth in height of low birth weight infants was also more pronounced in social classes I and II than in other social classes. That is, the mean height deficits of low birth weight infants were decreased from 2.9 cm at age 7, to 1.6 cm at age 16, and 2.5 cm at age 23; the significant difference disappeared after age 16 in social classes I and II. Although such improving tendency was more pronounced among the preterm born infants, a similar growth pattern was observed among the term infants. Such improvement was not observed in the other social classes. CONCLUSION: The growth retardation in height by birth weight can be overcome by improved social conditions and proper health care from childhood to adulthood. PMID- 11207165 TI - Birth weight, subsequent growth, and cholesterol metabolism in children 8-12 years old born preterm. AB - AIMS: To test the hypothesis that plasma lipids, lipoproteins, and markers of cholesterol biosynthesis (lathosterol) and absorption efficiency (campesterol) in children aged 8-12 years are related to birth size and subsequent growth. METHODS: A total of 412 girls and boys weighing less than 1850 g at birth were studied. Birth weight, gestation, and weight at 18 months were recorded and followed up at 8-12 years. Plasma total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, apolipoprotein A1, apolipoprotein B, triacylglycerol, lathosterol, and campesterol were measured. RESULTS: Birth weight for gestational age was positively related to plasma campesterol, and remained so after adjusting for current body size or fatness. Birth weight was negatively related to current plasma lathosterol but only after adjusting for current body size or fatness. For both lathosterol and campesterol the significant relation with birth size adjusted for current size indicates that the change in size between these points (postnatal upward centile crossing) was influential. These relations were absent for total cholesterol, lipoproteins, apolipoproteins, and triacylglycerol. CONCLUSION: Preterm children who were smaller for gestational age at birth had lower predicted cholesterol absorption efficiency 8-12 years later. Among children of the same current size, predicted endogenous cholesterol synthesis was higher and cholesterol absorption efficiency lower in those who showed the greatest increase in weight centile between birth and follow up. This finding was not confined to children with the smallest birth weights for gestational age. We suggest that both fetal and childhood growth relate to programming of cholesterol metabolism in children born preterm. PMID- 11207169 TI - Influences of ethnicity on perinatal and child mortality in the Netherlands. AB - AIMS: To investigate the differences in perinatal death and child mortality between different ethnic groups in the Netherlands. METHODS: Retrospective analysis of data collected between 1990 and 1993 in the national obstetric registry comprising 569 743 births. Retrospective analysis of all death certificates of 0 to 15 year old children routinely collected between 1979 and 1993, comprising 20 211 deaths. RESULTS: Black mothers had the highest perinatal death rate compared with indigenous Dutch mothers (odds ratio 2.2). Hindustanis (West Indian Asians) had an odds ratio of 1.4 and Mediterraneans 1.3. The increased rate for black and Hindustani women could be fully explained by preterm birth. In the Mediterranean group the differences were explained by teenage pregnancy, grand multiparity, and socioeconomic status rather than prematurity. The death rate of Turkish and Moroccan children was twice as high as that of native Dutch children. For the different diagnostic categories this was: infectious diseases, relative risk (RR) 2.2; hereditary (metabolic) disorders, RR 2.0; accidents and drowning, RR 1.9. One quarter of the Turkish and Moroccan children died while on holiday in their country of origin. Sudden infant death syndrome was twice as high for Turkish infants as for Dutch children and four times higher than for Moroccan infants. CONCLUSION: Ethnic minorities in the Netherlands have a higher perinatal and child mortality rate than the indigenous Dutch. Apart from socioeconomic differences, sociocultural and lifestyle factors play an important role. PMID- 11207170 TI - Idiopathic thrombocytopenic purpura and MMR vaccine. AB - A CAUSAL ASSOCIATION BETWEEN MEASLES: mumps-rubella (MMR) vaccine and idiopathic thrombocytopenic purpura (ITP) was confirmed using immunisation/hospital admission record linkage. The absolute risk within six weeks of immunisation was 1 in 22 300 doses, with two of every three cases occurring in the six week post immunisation period being caused by MMR. Children with ITP before MMR had no vaccine associated recurrences. PMID- 11207172 TI - Five year follow up of vertically HIV infected children in a randomised double blind controlled trial of immediate versus deferred zidovudine: the PENTA 1 trial. AB - A total of 195 children were randomised to zidovudine (immediate) or matching placebo (deferred) in a multicentre double blind trial in vertically HIV infected children with early disease (the PENTA 1 trial). Median follow up in the blinded phase was 1.9 years. Thereafter, individual children were unblinded following the results of adult trials showing a benefit of combination antiretroviral therapy (ART) over monotherapy, but follow up continued and is reported here until December 1998 (total follow up 4.6 years). Median time to starting ART in the deferred group was 2.7 years; 19% of deferred children had not started ART by 1999. Throughout follow up, the percentage of time spent on no ART, monotherapy, dual, and triple ART was 21%, 44%, 29%, and 6% respectively for immediate and 62%, 12%, 18%, and 8% for deferred groups. During the blinded phase eight (7.8%) immediate and 12 (13.3%) deferred children developed AIDS or died (log rank p = 0.24); overall 21 immediate and 20 deferred children progressed. In an analysis including all children regardless of original allocation, the risk of progression to AIDS or death, adjusting for age and time since trial entry was significantly lower during 1997-98 (2.4 per 100 child years) than during 1992-96 (6.6 per 100 child years), most likely a result of increased use of combination ART. PMID- 11207173 TI - Double blind, randomised controlled clinical trial of hypo-osmolar oral rehydration salt solution in dehydrating acute diarrhoea in severely malnourished (marasmic) children. AB - AIMS: To compare the clinical efficacy of hypo-osmolar oral rehydration salt (ORS) solution (224 mmol/l) and standard ORS solution (311 mmol/l) in severely malnourished (marasmic) children having less than 60% Harvard standard weight for age with dehydrating acute watery diarrhoea. METHODS: In a double blind, randomised, controlled trial, 64 children aged 6-48 months were randomly assigned standard (n = 32) or hypo-osmolar ORS (n = 32). RESULTS: Stool output (52.3 v 96.6 g/kg/day), duration of diarrhoea (41.5 v 66.4 hours), intake of ORS (111.5 v 168.9 ml/kg/day), and fluid intake (214.6 v 278.3 ml/kg/day) were significantly less in the hypo-osmolar group than in the standard ORS group. Percentage of weight gain on recovery in the hypo-osmolar group was also significantly less (4.3 v 5.4% of admission weight) than in the standard ORS group. A total of 29 (91%) children in the standard ORS group and 32 (100%) children in the hypo osmolar group recovered within five days of initiation of therapy. Mean serum sodium and potassium concentrations on recovery were within the normal range in both groups. CONCLUSION: Our findings suggest that hypo-osmolar ORS has beneficial effects on the clinical course of dehydrating acute watery diarrhoea in severely malnourished (marasmic) children. Furthermore, children did not become hyponatraemic after receiving hypo-osmolar ORS. PMID- 11207175 TI - Shared decision making in pediatrics. PMID- 11207174 TI - Randomised controlled trial of three day versus 10 day intravenous antibiotics in acute pyelonephritis: effect on renal scarring. AB - BACKGROUND: Acute pyelonephritis often leaves children with permanent renal scarring. AIMS: To compare the prevalence of scarring following initial treatment with antibiotics administered intravenously for 10 or three days. METHODS: In a prospective two centre trial, 220 patients aged 3 months to 16 years with positive urine culture and acute renal lesions on initial DMSA scintigraphy, were randomly assigned to receive intravenous ceftriaxone (50 mg/kg once daily) for 10 or three days, followed by oral cefixime (4 mg/kg twice daily) to complete a 15 day course. After three months, scintigraphy was repeated in order to diagnose renal scars. RESULTS: Renal scarring developed in 33% of the 110 children in the 10 day intravenous group and 36% of the 110 children in the three day group. Children older than 1 year had more renal scarring than infants (42% (54/129) and 24% (22/91), respectively). After adjustment for age, sex, duration of fever before treatment, degree of inflammation, presence of vesicoureteric reflux, and the patients' recruitment centres, there was no significant difference between the two treatments on renal scarring. During follow up, 15 children had recurrence of urinary infection with no significant difference between the two treatment groups. CONCLUSION: In children with acute pyelonephritis, initial intravenous treatment for 10 days, compared with three days, does not significantly reduce the development of renal scarring. PMID- 11207176 TI - Electroencephalographic and clinical features of cerebral malaria. AB - BACKGROUND: Seizures are a prominent feature of childhood cerebral malaria, and are associated with an increased risk of death and neurological sequelae. We present the electroencephalographic (EEG) findings from a detailed clinical and electrophysiological study. METHODS: Children with cerebral malaria had EEGs recorded within six hours of admission, and at 12 hourly intervals until recovery of consciousness. Ten deeply comatose children underwent intracranial pressure monitoring. Children were not mechanically ventilated, which made it possible to directly correlate the clinical and EEG findings. RESULTS: Of 65 children aged 9 months and above, 40 had one or more seizures, and 18 had an episode of status epilepticus. Most seizures were partial motor, and spike wave activity consistently arose from the posterior temporo-parietal region, a border zone area lying between territories supplied by the carotid and vertebrobasilar circulations. Fifteen children had seizures that were clinically subtle or electrographic. Clinical seizures were associated with an abrupt rise in intracranial pressure. Fifty children recovered fully, seven died, and eight had persistent neurological sequelae. Initial EEG recordings of very slow frequency, or with background asymmetry, burst suppression, or interictal discharges, were associated with an adverse outcome. CONCLUSIONS: Serial EEG recording has uncovered a range of clinical, subtle, and electrographic seizures complicating childhood cerebral malaria, and has emphasised their importance in the pathogenesis of coma. Further work is required to determine the most appropriate regimen for the prophylaxis and treatment of seizures in cerebral malaria, in order to improve outcome. PMID- 11207177 TI - Exercise induced hypoglycaemic hyperinsulinism. AB - BACKGROUND: Hyperinsulinism in childhood is often caused by genetic defects involving the regulation of insulin secretion leading to recurrent episodes of hypoglycaemia. We report two patients with exercise induced hypoglycaemia. METHODS: Standardised short exercise tests with frequent blood glucose and plasma insulin measurements were performed in the patients and young healthy controls. RESULTS: Short term exercise resulted in insulin induced hypoglycaemia 15 to 50 minutes after the end of exercise. A massive burst of insulin secretion was observed within a few minutes of the start of exercise in both patients. By contrast glucose and insulin concentrations remained unchanged in healthy controls. CONCLUSIONS: Hyperinsulinaemic hypoglycaemia after moderate physical exercise represents a rarely described phenotype of hyperinsulinism with an as yet unknown defect in the regulation of insulin secretion. It should be suspected in individuals with recurrent exercise related syncope or disturbance of consciousness. PMID- 11207178 TI - Prognosis of patients with acute renal failure without cardiopathy. AB - BACKGROUND: The outcome for children with acute renal failure (ARF) may be poor. However, relatively few published studies have considered prognosis of these patients. METHODS: We prospectively studied, from 1978 to 1998, 92 such children without heart disease to try to identify risk factors for mortality. RESULTS: Forty five per cent of children with tumours, shock, and other causes died compared with none of those with a primary urinary tract related problem. ARF did not seem to be the cause of death in any case. Univariate analysis showed that in the non-primary urinary problem group (55 cases), patients with hypotension, high values of BUN or creatinine, or who needed mechanical ventilation or dialysis, had a poor outcome. Multivariate analysis showed that probability of death can be estimated using the following score: -0.02 + 0.28 (hypotension) + 0.19 (ventilation) + 0.27 (dialysis) + 0.01 (BUN). CONCLUSIONS: Mortality of patients with ARF was related to aetiology, the need for dialysis and/or ventilator use, hypotension, and BUN values. PMID- 11207179 TI - Pancreatic dysfunction in severe obesity. AB - AIMS: To investigate pancreatic function in children attending an obesity clinic. METHODS: Thirty six children (of which 34 were white) with severe obesity of prepubertal onset (body mass index more than +2 SDS) were reviewed clinically and dysmorphologically, with assessment of pancreatic function. RESULTS: Eight had dysmorphic features and 13 had learning difficulties. Four of 17 prepubertal children had hyperinsulinaemia and seven had hyperproinsulinaemia. All 19 pubertal children had hyperinsulinaemia, 14 had hyperproinsulinaemia, and one had type II diabetes. CONCLUSIONS: Metabolic abnormalities predictive of type II diabetes occur in severely obese white children. PMID- 11207180 TI - Retinal haemorrhage and fatal stroke in an infant with fibromuscular dysplasia. AB - Non-accidental injury should be suspected and excluded in any infant found to have intracranial and retinal haemorrhage of unknown aetiology. This can be a sensitive issue for both medical staff and parents. We present a case in which the underlying cause of intracranial and retinal haemorrhage was fibromuscular dysplasia. It was a diagnosis made only at postmortem examination and it illustrates the diagnostic difficulty such cases may present. PMID- 11207182 TI - Acute urinary retention: an unusual presentation of acute appendicitis in a 3 year old boy. PMID- 11207181 TI - Identifying futility in a paediatric critical care setting: a prospective observational study. AB - AIMS: To determine the extent of futile care provided to critically ill children admitted to a paediatric intensive care setting. METHODS: Prospective evaluation of consecutive admissions to a 20 bedded multidisciplinary paediatric intensive care unit of a North London teaching hospital over a nine month period. Three previously defined criteria for futility were used: (1) imminent demise futility (those with a mortality risk greater than 90% using the Paediatric Risk of Mortality (PRISM II) score); (2) lethal condition futility (those with conditions incompatible with long term survival); and (3) qualitative futility (those with unacceptable quality of life and high morbidity). RESULTS: A total of 662 children accounting for 3409 patient bed days were studied. Thirty four patients fulfilled at least one of the criteria for futility, and used a total of 104 bed days (3%). Only 33 (0.9%) bed days were used by patients with mortality risk greater than 90%, 60 (1.8%) by patients with poor long term prognosis, and 16 (0.5%) by those with poor quality of life. Nineteen of 34 patients died; withdrawal of treatment was the mode of death in 15 (79%). CONCLUSIONS: Cost containment initiatives focusing on futility in the paediatric intensive care unit setting are unlikely to be successful as only relatively small amounts of resources were used in providing futile care. Paediatricians are recognising futility early and may have taken ethically appropriate measures to limit care that is futile. PMID- 11207183 TI - Parental compliance with home cardiorespiratory monitoring. AB - AIMS: To evaluate parental compliance with home cardiorespiratory monitoring of premature infants with apnoea, siblings of infants who died of sudden infant death syndrome (SIDS), and infants with an apparent life threatening event (ALTE), during the first month of use. METHODS: A retrospective review of the first month's recordings was conducted on 39 premature infants with apnoea, 13 siblings of SIDS, and 16 infants with ALTE. All infants were singletons. Recommendations during the study period (1992-1994) were for daily use for 23 hours per day. Measurements were average daily hours of use and consistency of use (daily or variable). Gestational age, maternal age, and socioeconomic status as measured by receipt of public assistance were also recorded. RESULTS: Siblings of SIDS were monitored for fewer hours than were premature or ALTE infants. Only 54% of sibings of SIDS were monitored daily, compared to 87% of premature infants and 93% of ALTEs. Within each diagnostic category socioeconomic status did not affect average hours of monitoring. Consistency of use was more evident in those with private insurance, although the trend did not reach significance. CONCLUSIONS: Parents of infants with apnoea of prematurity or ALTE are highly compliant with cardiorespiratory monitoring recommendations in the first month of monitor usage. Siblings of SIDS are monitored for fewer hours and are less likely to be monitored on a daily basis. PMID- 11207184 TI - Simultaneous monitoring of gastric and oesophageal pH reveals limitations of conventional oesophageal pH monitoring in milk fed infants. AB - BACKGROUND: Monitoring oesophageal pH conventionally detects "acid reflux" (pH less than 4). The pH of the gastric contents determines whether or not reflux can be detected. AIM: To monitor gastric and oesophageal pH simultaneously in order to determine the effect of milk feeds on gastric pH and how this would influence interpretation of the oesophageal pH record. METHODS: Milk fed infants for whom oesophageal pH monitoring was requested underwent simultaneous gastric and oesophageal pH monitoring using a dual channel pH probe. RESULTS: Twenty of 24 records were technically satisfactory. Mean reflux index was 1.0%, range 0.0 4.0%. Gastric pH was less than 4 for 24.5% (range 0.6-69.1%) of the total time. The average time the gastric pH was greater than 4 after feeds was 130 minutes (range 29-212 minutes). The corrected reflux index (limited to the time the gastric pH was less than 4) was 2.6% (range 0.0-11.0%). CONCLUSION: The pH of the gastric contents may be greater than 4 for prolonged intervals, during which oesophageal pH monitoring using current criteria cannot detect reflux nor correlate it with clinical events. A low reflux index may reflect prolonged buffering of gastric acidity rather than the absence of reflux. PMID- 11207185 TI - Ion channels and neurology. PMID- 11207186 TI - Negative feedback regulation of the secretion and actions of gonadotropin releasing hormone in males. AB - This minireview considers the state of knowledge regarding the interactions of testicular hormones to regulate the secretion and actions of GnRH in males, with special focus on research conducted in rams and male rhesus monkeys. In these two species, LH secretion is under the negative feedback regulation of testicular steroids that act predominantly within the central nervous system to suppress GnRH secretion. The extent to which these actions of testicular steroids result from the direct actions of testosterone or its primary metabolites, estradiol or dihydrotestosterone, is unclear. Because GnRH neurons do not contain steroid receptors, the testicular steroids must influence GnRH neurons via afferent neurons, which are largely undefined. The feedback regulation of FSH is controlled by inhibin acting directly at the pituitary gland. In male rhesus monkeys, the feedback regulation of FSH secretion is accounted for totally by the physiologically relevant form of inhibin, which appears to be inhibin B. In rams, the feedback regulation of FSH secretion involves the actions of inhibin and testosterone and interactions between these hormones, but the physiologically relevant form of inhibin has not been determined. The mechanisms of action for inhibin are not known. PMID- 11207187 TI - Plasma inhibin A in heifers: relationship with follicle dynamics, gonadotropins, and steroids during the estrous cycle and after treatment with bovine follicular fluid. AB - The relationship between follicle growth and plasma inhibin A, FSH, LH, estradiol (E), and progesterone was investigated during the normal bovine estrous cycle and after treatment with steroid-free bovine follicular fluid (bFF) to arrest follicle development. In the first study, four heifers were monitored over three prostaglandin (PG)-synchronized cycles. Blood was collected every 2-8 h, and ovaries were examined daily by ultrasonography. Inhibin A was measured using a modified enzyme-linked immunosorbent assay that employed a new monoclonal antibody against the alpha subunit of bovine inhibin. Plasma inhibin A ( approximately 50 pg/ml before luteolysis) rose steadily during the induced follicular phase (P < 0.05) to a peak ( approximately 125 pg/ml) coincident with the preovulatory E/LH/FSH surge. After ovulation, inhibin A fell sharply (P < 0.05) to a nadir ( approximately 55 pg/ml) coincident with the secondary FSH rise. During the next 3 days, inhibin A increased to approximately 90 pg/ml in association with growth of the new dominant follicle (DF). Plasma E also rose twofold during this period, whereas FSH fell by approximately 50%. Inhibin A was negatively correlated with FSH (r = -0.37, P < 0.001) and positively correlated with E (r = 0.49, P < 0.0001). Observations on eight cycles (two cycles/heifer), in which growth of the ovulatory DF was monitored from emergence to ovulation, showed that the first-wave DF (DF1) ovulated in three cycles and the second-wave DF (DF2) in five cycles. After PG, plasma inhibin A and E increased similarly in both groups, with concomitant falls in FSH. In the former group, the restricted ability of DF1 to secrete both inhibin A and E was restored after luteolysis. Results indicate that dynamic changes in the secretion of both E and inhibin A from the DF contribute to the fall in FSH during the follicular phase and to the generation and termination of the secondary FSH surge, both of which play a key role in follicle selection. In the second study, bFF (two dose levels) was administered to heifers (n = 3-4) for 60 h starting from the time of DF1 emergence. Both doses suppressed FSH (P < 0.05) and blocked DF1 growth to the same extent (P < 0.01), although inhibin A levels were only marginally raised by the lower dose (not significant compared to controls). The high bFF dose raised (P < 0.001) inhibin A to supraphysiological levels ( approximately 1 ng/ml). A large "rebound" rise in FSH occurred within 1 day of stopping both treatments, even though the inhibin A level in the high-dose bFF group was still approximately threefold higher than that in controls. This indicates that desensitization of gonadotropes to inhibin negative feedback is a contributory factor, together with reduced ovarian output of E, in generation of the post-bFF rebound in FSH. PMID- 11207188 TI - Ectopic transplantation of equine invasive trophoblast. AB - A system for transplanting invasive equine trophoblast (i.e., chorionic girdle) to ectopic sites has been developed as a means to study the differentiation of this tissue and to assess maternal immune responses to the conceptus tissue in a site outside the uterus. Chorionic girdle was isolated from Day 33 to 34 conceptuses and surgically placed into the vulvar mucosa or subdermal skin of recipient mares. Biopsy specimens of the graft sites for immunohistochemical staining were taken at weekly or biweekly intervals after grafting. Serum samples were collected from each recipient and tested for antibody to donor major histocompatibility complex (MHC) class I antigens using the lymphocyte microcytotoxicity assay. Transplanted trophoblast cells expressed differentiation markers associated with invading chorionic girdle and endometrial cup cells. The transplanted trophoblast cells were also labeled by an antibody to eCG. Strong cellular and humoral immune responses to the transplanted tissue were mounted by the recipients, similar to those occurring during normal equine pregnancy. Despite these responses, the invasive trophoblast transplants survived for at least 28 days after grafting and downregulated MHC class I antigens, as do the mature endometrial cup cells in equine pregnancy. These findings suggest that invasive equine trophoblast has the capacity to differentiate fully in equine nonuterine tissues, and that it can evade maternal immune responses independent of the physiological state of pregnancy and in sites other than the uterus. PMID- 11207190 TI - Telomerase activity in early bovine embryos derived from parthenogenetic activation and nuclear transfer. AB - This study examined the telomerase activity in preimplantation bovine embryos derived from either parthenogenetic activation or nuclear transfer. Telomeres are the DNA-protein structures located at the ends of eukaryotic chromosomes. Telomerase is the ribonuclear enzyme that helps to restore telomere length by synthesizing telomeric DNA repeat (5'-TTAGGG-3') from its own RNA template. Without telomerase activity, telomeres shorten with each cell division through conventional DNA replication. In most mammalian species, telomerase activity is present in germ cells but not in somatic cells. Previously, we reported the dynamics of telomerase activity in bovine in vitro fertilized (IVF) embryos. In the present study, we examined the telomerase activity in bovine embryos derived either from parthenogenetic activation or somatic cell nuclear transfer (i.e., cloning). Embryos from both sources were harvested at different stages, from zygote to blastocyst. Telomerase activity in embryos derived from parthenogenetic activation and nuclear transfer showed a dynamic profile similar to that of those derived from IVF. Telomerase activity was detected in embryos at all stages examined, with the highest level in the blastocyst stage, regardless of the method of embryo production. PMID- 11207189 TI - Na+ reabsorption in cultured rat epididymal epithelium via the Na+/nucleoside cotransporter. AB - The effect of nucleoside on Na+ reabsorption via Na+/nucleoside cotransporter in cultured rat epididymal epithelia was studied by short-circuit current (Isc) technique. Guanosine added apically stimulated Isc in a dose-dependent manner, with a median effective concentration (EC50) of 7 +/- 2 microM (mean +/- SEM). Removal of Na+ from the apical bathing solution or pretreatment with a nonspecific Na+/nucleoside cotransporter inhibitor, phloridzin, completely blocked the Isc response to guanosine. Moreover, the guanosine response was abolished by pretreatment of the tissue with ouabain, a Na+/K+-ATPase inhibitor, suggesting the involvement of Na+/nucleoside cotransporter on the apical side and Na+/K+-ATPase on the basolateral side in Na+ reabsorption. In contrast, the Isc response to guanosine was not affected after desensitization of purinoceptors by ATP. Addition of the Na+/K+/2Cl- symport inhibitor bumetanide to the basolateral side or the nonspecific Cl- channel blocker diphenylamine-2-carboxylate to the apical side showed no effect on the Isc response to guanosine, excluding stimulation of Cl- secretion by guanosine as the cause of the guanosine-induced Isc. The Isc response to purine nucleoside (guanosine and inosine) was much higher than that to pyrimidine nucleoside (thymidine and cytidine). Consistent with substrate specificity, results of reverse transcription-polymerase chain reaction revealed mRNA for concentrative nucleoside transporter (CNT2), which is a purine nucleoside-selective Na+/nucleoside cotransporter in the epididymis, but not for CNT1. It is suggested that the Na+/nucleoside cotransporter (i.e., CNT2) may be one of the elements involved in Na+ and fluid reabsorption in the epididymis, thereby providing an optimal microenvironment for the maturation and storage of spermatozoa. PMID- 11207191 TI - Steroidogenic factor-1 contributes to the cyclic-adenosine monophosphate down regulation of human SRY gene expression. AB - In mammals, male sex determination is initiated by SRY (sex-determining region of the Y chromosome) gene expression and followed by testicular development. This study describes specific down-regulation of the human SRY gene transcription by cAMP stimulation using reverse transcription-polymerase chain reaction experiments. Using transfection experiments, conserved nuclear hormone receptor (NHR1) and Sp1 consensus binding sites were identified as essential for this cAMP transcriptional response. Steroidogenic factor-1 (SF-1), a component of the sex determination cascade, binds specifically to the NHR1 site and activates the SRY promoter. Activation of SF-1 was abolished by cAMP pretreatment of the cells, suggesting a possible effect of cAMP on the SF-1 protein itself. Indeed, human SF 1 protein contains at least two in vitro cAMP-dependent protein kinase (PKA) phosphorylation sites, leading after phosphorylation to a modification of both DNA-binding activity and interaction with general transcription factors such as Sp1. Taken together, these data suggest that cAMP responsiveness of human SRY promoter involves both SF-1 and Sp1 sites and could act via PKA phosphorylation of the SF-1 protein itself. PMID- 11207192 TI - Expression of Fas/Fas ligand by decidual leukocytes in hydatidiform mole. AB - Complete hydatidiform moles are entirely paternally derived and, therefore, represent a complete intrauterine allograft that might be expected to provoke an altered maternal immune response compared with that of normal pregnancy. Uterine decidua contains a large leukocyte population, of which 10%-20% are T lymphocytes. Fas ligand (FasL) expression by placental trophoblast may induce apoptosis of Fas+ lymphocytes, thereby facilitating immune tolerance and survival of the molar trophoblast. Our previous studies have shown an increase in activated CD4+ decidual T cells in molar pregnancy compared with normal pregnancy. This study was designed to characterize and quantitate Fas/FasL expression by decidual leukocytes in complete and partial hydatidiform mole compared with that in normal early pregnancy using single and double immunohistochemical labeling (i.e., avidin-biotin-peroxidase and avidin-biotin alkaline phosphatase). A significant increase was found in Fas and FasL expression by decidual CD4+ T cells in complete (Fas+, P = 0.0106; FasL+, P = 0.0081) and partial (Fas+, P = 0.0131; FasL+, P = 0.0051) hydatidiform moles, as was a significant decrease in Fas expression by decidual CD8+ T cells in complete (P = 0.0137) and partial (P = 0.0202) hydatidiform mole compared with normal early pregnancy. The implications of altered Fas/FasL status of decidual T-cell subsets in hydatidiform mole are also discussed. PMID- 11207193 TI - Production of 25-hydroxycholesterol by testicular macrophages and its effects on Leydig cells. AB - Testicular macrophages secrete 25-hydroxycholesterol, which can be converted to testosterone by neighboring Leydig cells. The purposes of the present studies were to determine the mode of production of this oxysterol and its long-term effects on Leydig cells. Because oxysterols are produced both enzymatically and by auto-oxidation, we first determined if testicular macrophages possess cholesterol 25-hydroxylase mRNA and/or if macrophage-secreted products oxidize cholesterol extracellularly. Rat testicular macrophages had 25-hydroxylase mRNA and converted 14C-cholesterol to 14C-25-hydroxycholesterol; however, radiolabeled cholesterol was not converted to 25-hydroxycholesterol when incubated with medium previously exposed to testicular macrophages. Exposure of Leydig cells to 10 microg/ml of 25-hydroxycholesterol, a dose within the range known to result in high basal production of testosterone when tested from 1 to 6 h, completely abolished LH responsiveness after 2 days of treatment. Because 25 hydroxycholesterol is toxic to many cell types at 1-5 microg/ml, we also studied its influence on Leydig cells during 4 days in culture using a wide range of doses. Leydig cells were highly resistant to the cytotoxic effects of 25 hydroxycholesterol, with no cells dying at 10 microg/ml and only 50% of cells affected at 100 microg/ml after 2 days of treatment. Similar conditions resulted in 100% death of a control lymphocyte cell line. These results demonstrate that 1) testicular macrophages have mRNA for cholesterol 25-hydroxylase and can convert cholesterol into 25-hydroxycholesterol, 2) macrophage-conditioned medium is not capable of auto-oxidation of cholesterol, 3) Leydig cells are highly resistant to the cytotoxic influences of 25-hydroxycholesterol, and 4) long-term treatment with high doses of 25-hydroxycholesterol results in loss of LH responsiveness. These results support the concept that testicular macrophages enzymatically produce 25-hydroxycholesterol that not only is metabolized to testosterone by Leydig cells when present at putative physiological levels but also may exert inhibitory influences on Leydig cells when present for extended periods at very high concentrations that may occur under pathological conditions. PMID- 11207194 TI - Effects of neonatal progestin exposure on female reproductive tract structure and function in the adult ewe. AB - Endometrial glands are present in all mammalian uteri and produce secretions that are hypothesized to support conceptus (i.e., embryo/fetus and placental membranes) survival and development. In sheep, endometrial gland morphogenesis occurs postnatally and can be epigenetically ablated by chronic neonatal exposure to a progestin from birth, thereby producing an adult uterine gland knock-out (UGKO) phenotype. This study determined the long-term effects of neonatal progestin exposure on adult ovine reproductive tract structure and function. Neonatal ewes were exposed to norgestomet (Nor) from birth to 32 wk of age. Unexposed ewes served as controls. After puberty, adult Nor-treated (n = 6) and control (n = 6) ewes were repeatedly bred at estrus (Day 0) to intact rams of proven fertility. In contrast to a pregnancy rate of 80% for control ewes, pregnancy was never detected on Day 25 after mating (or thereafter) in bred UGKO ewes. Control and Nor-treated ewes were then bred and necropsied on Day 9. Similar numbers of hatched blastocysts were present in uterine flushings from control and Nor-treated ewes. Weights of the ovaries and cervices were not affected by treatment. No histoarchitectural differences between control and Nor treated ewes were detected for ovaries, oviducts, cervices, or vaginae. However, uterocervical and uterine weight as well as uterine horn length were less for Nor treated ewes. The uteri of Nor-treated ewes were devoid of endometrial glands and lacked the stromal delineation characteristic of intercaruncular endometrium in control ewes. Endometrial width, area, and lumenal epithelial length were decreased in uteri from Nor-treated ewes, but myometrial width and morphology were not affected. Expression of a number of mRNAs that are expressed predominantly in the endometrial epithelia was not different between uteri from control and from Nor-treated ewes. Collectively, these results indicate that neonatal exposure of ewes to a progestin from birth appears to only affect development of the uterus and not any extrauterine reproductive tract tissues. The infertility of the UGKO ewes appears to result from a lack of endometrial glands and, by extension, of their secretions that are required to support growth and development of peri-implantation conceptuses. PMID- 11207195 TI - Cloning of rainbow trout egg envelope proteins: members of a unique group of structural proteins. AB - All vertebrate eggs are surrounded by an extracellular envelope that protects the egg and is vital for a successful fertilization. The terminology and functions of the egg envelope vary in different vertebrate groups, but the envelope itself is consistently composed of a few major proteins that are deposited around the oocyte during oocyte growth. Here, we describe the deduced amino acid sequences and tissue expression patterns of the three major egg envelope proteins for rainbow trout (Oncorhynchus mykiss). All three vitelline envelope proteins (VEPs) are expressed in the livers of both male and female fish, with higher expression in females. In addition, VEPgamma mRNA is also detected in the female gonads. To our knowledge, this is the first time that expression of a VEP protein gene has been demonstrated to occur in more than one organ. Sequence comparison reveals that all three VEP proteins share distinct homology with their amphibian, avian, and mammalian counterparts. Whereas mammalian zona pellucida protein 3 isoforms contain two conserved serines needed for sperm binding, these are not conserved in teleost species, in which sperm entry is restricted to the micropyle. Besides the difference in VEPgamma sperm-binding function, the high sequence homology suggests that the egg envelope proteins from these distinct vertebrate groups share a common ancestry and form a unique group of structural proteins. PMID- 11207196 TI - Corticosteroid-binding globulin status at the fetomaternal interface during human term pregnancy. AB - The status of the corticosteroid-binding globulin (CBG) at the fetomaternal interface, especially in the maternal intervillous blood space (I), was investigated and compared to that of CBG in the maternal (M) and fetal (umbilical arteries [A] and vein [V]) peripheral circulations at term. Immunoquantitation of plasma CBG showed that the CBG concentration in I was 30% less than that in M (P < 0.001) and threefold higher than that in umbilical cord blood (P < 0.001). The microheterogeneity of CBG studied by immunoaffinoelectrophoresis in the presence of concanavalin A and Western blotting indicated that the CBG in I was mainly of maternal origin and different from fetal CBG. A CBG mRNA, but no classic 50- to 59-kDa CBG, was found in isolated term trophoblastic cells. The steroid environment of the CBG in I differed greatly from that in the peripheral maternal and fetal circulations, because the progesterone:cortisol molar ratio in I was 75 fold higher than that in M and 7- to 10-fold higher than that in the fetal circulation. Binding studies revealed that the affinity constants of CBG for cortisol in I, A, and V were significantly lower than that in M plasma (P < 0.02) in their respective hormonal contexts. The binding parameters for I-CBG stripped of endogenous steroids and lipids were close to those for M-CBG but different from those of fetal CBG (P < 0.001). These data reflect the physiological relevance of the CBG-steroid interaction, especially with very CBG-loaded progesterone at the fetomaternal interface during late pregnancy. PMID- 11207197 TI - Morphological and biochemical changes of isolated chicken egg-envelope during sperm penetration: degradation of the 97-kilodalton glycoprotein is involved in sperm-driven hole formation on the egg-envelope. AB - The chicken egg-envelope is made of two major glycoprotein components, which are designated as gp97 and gp42 (after their molecular masses). To elucidate how these two components are involved in macromolecular organization of the chicken egg-envelope, the isolated egg-envelope was characterized by immunochemical and biochemical methods. The gp97 was suggested to be a homologue of mouse ZPB based on the similarities of N-terminal and internal sequences. Immunoblotting using anti-gp97 monoclonal antibodies and two-dimensional gel electrophoresis with or without mercaptoethanol treatment revealed that gp97 formed a homodimer through disulfide bonds, whereas gp42 did not. Under indirect immunofluorescence microscopy, the anti-gp97 antibody visualized indistinct, small spots on the egg envelope, whereas the anti-gp42 antibody showed a meshwork of blurry, fibrous structures. The hole formation on the egg-envelope by in vitro sperm penetration was completely inhibited by two anti-gp97 monoclonal antibodies. Interestingly, the anti-gp97 monoclonal antibodies blocked the proteolysis not only of gp97 but also of gp42 during incubation of the egg-envelope with either sperm or the crude chicken acrosin. Taken together, these results indicate that gp97 may play pivotal roles not only in constitution of the macromolecular organization of the egg-envelope but also in triggering hydrolysis of the egg-envelope during sperm penetration. PMID- 11207198 TI - Stromal-epithelial interactions modulate estrogen responsiveness in normal human endometrium. AB - The coculture of endometrial epithelial cells (EEC) with stromal cells (ESC) allows achievement of an improved in vitro system for studying interactions between cells via soluble signals. The purpose of this study was to investigate whether 17beta-estradiol and insulin can induce proliferation of EEC through ESC secreted factors. No evidence of estrogen-induced EEC proliferation has been reported so far in the conventional culture methods. To this end, we used an in vitro bicameral coculture model where human EEC were grown on extracellular matrix-coated inserts applied in dishes containing ESC. Proliferation was assessed by tritiated thymidine incorporation. Homogeneity of endometrial cell populations was ascertained immunocytochemically. 17beta-estradiol did not induce any proliferative effect on EEC cultured alone. Endometrial epithelial cell proliferation was significantly enhanced in EEC/ESC cocultures; moreover, it was further increased by 17beta-estradiol addition. Insulin increased proliferation in EEC cultured alone, but again the effect was more pronounced in EEC/ESC cocultures. Coincubation of 17beta-estradiol and an antibody against insulin-like growth factor I (IGF I) led to neutralization of ESC-mediated EEC proliferation. This work provides evidence that the effect of 17beta-estradiol on human EEC proliferation may be mediated at least in part through ESC-secreted IGF I. We also showed that insulin effect is also partially due to ESC activation. PMID- 11207199 TI - Alterations in intrafollicular regulatory factors and apoptosis during selection of follicles in the first follicular wave of the bovine estrous cycle. AB - Changes in follicular fluid (FF) concentrations of estradiol, inhibin forms, and insulin-like growth factor binding proteins (IGFBPs), percentage of apoptotic granulosa cells (%A), and follicular size for individual follicles in a growing cohort were determined throughout the first wave of follicular development during the bovine estrous cycle and related to FSH decline. Four groups of heifers (n = 31) were ovariectomized between Days 1.5 and 4.5 of the estrous cycle at 5 +/- 1, 33 +/- 2, 53 +/- 1, and 84 +/- 2 h after the periovulatory peak in FSH concentrations. Follicles > or = 2.5 mm were dissected, measured, and FF aspirated. The five largest follicles were ranked based on their diameter (F1 to F5). Diameters of F1 to F5 were positively correlated with interval from FSH peak (r > or = 0.6, P < 0.05). Five hours after the FSH peak, follicular diameter and FF concentrations of estradiol, inhibins, and IGFBPs were similar for F1 to F5. From 5 to 33 h, amounts of the six precursor inhibin forms (> or = 48 kDa) increased (P < 0.05) in F1 follicles. The IGFBPs in F1 follicles remained low at all time periods. At 33 h, amounts of IGFBP-4 and -5 were higher (P < 0.05) in F4 and F5 compared with F1 follicles. At 84 h, IGFBP-2, -4, and -5 were increased (P < 0.05) in F3, F4, and F5 compared with F1. At 5, 33, or 53 h, %A was not different between follicles in any size class. At 84 h %A was increased (P < 0.05) in follicles <6 mm in diameter. However, at that time, %A did not differ between the selected DF and the largest subordinate follicle. For individual heifers, the selected DF at 84 h was largest in size, highest in estradiol, and lowest in IGFBP-2 and -4. The F1 follicle had highest estradiol in 23 of 27 heifers irrespective of stage of the wave and lowest IGFBP-4 in 19 of 21 heifers from 33 h. We concluded that the earliest intrafollicular changes that differentiate a dominant-like follicle from the growing cohort are enhanced capacity to produce estradiol and maintenance of low levels of IGFBPs. PMID- 11207200 TI - Generation of dwarf goat (Capra hircus) clones following nuclear transfer with transfected and nontransfected fetal fibroblasts and in vitro-matured oocytes. AB - The developmental potential of caprine fetal fibroblast nuclei after in vitro transfection and nuclear transfer (NT) into enucleated, in vitro-matured oocytes was evaluated. Fetal fibroblasts were isolated from Day 27 to Day 30 fetuses from a dwarf breed of goat (BELE: breed early lactate early). Cells were transfected with constructs containing the enhanced green fluorescent protein (eGFP) and neomycin resistance genes and were selected with G418. Three eGFP lines and one nontransfected line were used as donor cells in NT. Donor cells were cultured in Dulbecco minimum Eagle medium plus 0.5% fetal calf serum for 4-8 days prior to use in NT. Immature oocytes were recovered by laparoscopic ovum pick-up and matured for 24 h prior to enucleation and NT. Reconstructed embryos were transferred as cleaved embryos into synchronized recipients. A total of 27 embryos derived from transgenic cells and 70 embryos derived from nontransgenic cells were transferred into 13 recipients. Five recipients (38%) were confirmed pregnant at Day 35 by ultrasound. Of these, four recipients delivered five male kids (7.1% of embryos transferred) derived from the nontransfected line. One recipient delivered a female kid derived from an eGFP line (7.7% of embryos transferred for that cell line). Presence of the eGFP transgene was confirmed by polymerase chain reaction, Southern blotting, and fluorescent in situ hybridization analyses. Nuclear transfer derivation from the donor cells was confirmed by single-strand confirmation polymorphism analysis. These results demonstrate that both in vitro-transfected and nontransfected caprine fetal fibroblasts can direct full-term development following NT. PMID- 11207201 TI - Regulation of cyclic guanosine monophosphate-dependent protein kinase in human uterine tissues during the menstrual cycle. AB - Contractility of uterine smooth muscle is essential for the cyclic shedding of the endometrial lining and also for expulsion of the fetus during parturition. The nitric oxide (NO)-cGMP signaling pathway is involved in smooth muscle relaxation. The downstream target of this pathway essential for decreasing cytoplasmic calcium and muscle tone is the cGMP-dependent protein kinase (PKG). The present study was undertaken to localize expression of PKG in tissues of the female reproductive tract and to test the hypothesis that uterine smooth muscle PKG levels vary with the human menstrual cycle. Immunohistochemistry was used to localize PKG in myometrium, cervix, and endometrium obtained during proliferative and secretory phases. The PKG was localized to uterine and vascular smooth muscle cells in myometrium, stromal cells in endometrium, and a small percentage of cervical stromal cells. Using Western blot analysis and protein kinase activity assays, the expression of PKG was reduced significantly in progesterone-dominated uteri compared with myometrium from postmenopausal women or women in the proliferative phase. These findings support a role for PKG in the control of uterine and vascular smooth muscle contractility during the menstrual cycle. PMID- 11207202 TI - Formyl-methionyl-leucyl-phenylalanine induces prostaglandin E2 release from human amnion-derived WISH cells by phospholipase C-mediated [Ca+]i rise. AB - The presence of binding sites for formyl-methionyl-leucyl-phenylalanine (fMLP), its effect on prostaglandin E (PGE) release, and the signal transduction pathway activated by the peptide were investigated in human amnion-derived WISH cells. Our results demonstrate that specific binding sites for fMLP are present on WISH cells and that the peptide induces a significant increase of prostaglandin (PG)E2 release. The kinetic properties of binding are similar to those previously found in amnion tissue prior to the onset of labor, i.e., only one population of binding sites with low affinity for the peptide is present. Binding of 3H-fMLP in WISH cells is inhibited by N-t-butoxycarbonyl-methionyl-leucyl-phenylalanine, an fMLP receptor antagonist, with an IC50 value very close to that shown by nonlaboring amnion. The fMLP-induced PGE2 output is inhibited by indomethacin, quinacrine, and U-73122, inhibitors of cyclooxygenase, phospholipase A2, and phospholipase C, respectively. As regards the transduction pathway activated by fMLP, we demonstrate that phospholipase C activation, followed by an increase of intracellular calcium concentration ([Ca2+]i), is involved in response to the peptide. Our results add further evidence to the role of proinflammatory agents in the determination of labor. Furthermore, because WISH cells appear to behave like nonlaboring amnion tissue, they represent the ideal candidate for in vitro investigation of the events triggering the mechanism of delivery. PMID- 11207203 TI - Inactivation of M-phase promoting factor at exit from first embryonic mitosis in the rat is independent of cyclin B1 degradation. AB - Exit from M-phase and completion of cell division requires inactivation of M phase promoting factor (MPF), a heterodimer composed of the regulatory cyclin B1 and the catalytic p34cdc2 kinase. Inactivation of MPF is associated with cyclin B1 degradation that is brought about by the ubiquitin-proteasome pathway. Our study examined the role of the proteasome in the first mitosis of rat embryos and its participation in the regulation of cyclin B1 degradation and MPF inactivation. We show that in the early zygote the proteasome is evenly distributed in the ooplasm and the nucleus, whereas during mitosis it accumulates on the spindle apparatus. We further demonstrate that inhibition of proteasomal catalytic activity prevents 1-cell embryos from undergoing mitosis. This mitotic arrest is associated with the presence of relatively high amounts of cyclin B1, which unexpectedly does not result in elevated MPF activity. Our findings strongly imply that completion of the first embryonic division depends on proteasomal degradation and that cyclin B1 is included among its target proteins. They also provide the first evidence that MPF inactivation at this stage of development is not solely dependent upon cyclin B1 degradation and is insufficient to allow the formation of the 2-cell embryo. PMID- 11207204 TI - Dynamic events are differently mediated by microfilaments, microtubules, and mitogen-activated protein kinase during porcine oocyte maturation and fertilization in vitro. AB - The role of microfilaments, microtubules, and mitogen-activated protein (MAP) kinase in regulation of several important dynamic events of porcine oocyte maturation and fertilization is described. Fluorescently labeled microfilaments, microtubules, and cortical granules were visualized using either epifluorescence microscopy or laser scanning confocal microscopy. Mitogen-activated protein kinase phosphorylation was revealed by Western immunoblotting. We showed that 1) microfilament disruption did not affect meiosis resumption and metaphase I meiotic apparatus formation but inhibited further cell cycle progression (chromosome separation) even though MAP kinase was phosphorylated; 2) cortical granule (CG) migration was driven by microfilaments (but not microtubules), and once the chromosomes and CGs were localized beneath the oolemma their anchorage to the cortex was independent of either microfilaments or microtubules; 3) neither microfilaments nor microtubules were involved in CG exocytosis during oocyte activation; 4) sperm incorporation was mediated by microfilaments, while pronuclear (PN) syngamy was controlled by microtubules rather than microfilaments; 5) spindle microtubule organization was temporally correlated with MAP kinase phosphorylation, while the extensive microtubule organization in the sperm aster that is required for PN apposition and syngamy occurred in the absence of MAP kinase activation; and 6) MAP kinase phosphorylation did not change either when microtubules were disrupted by nocodazole or when cytoplasmic microtubule asters were induced by taxol. The present study suggests that the role of the cytoskeleton during porcine oocyte maturation is similar to that of rodents, while the mechanisms of fertilization in pig resemble those of lower vertebrates. PMID- 11207205 TI - Actions of prostaglandin F2alpha and prolactin on intercellular adhesion molecule 1 expression and monocyte/macrophage accumulation in the rat corpus luteum. AB - Expression of intercellular adhesion molecule-1 (ICAM-1) and the accumulation of monocytes/macrophages are inflammatory events that occur during PRL (PRL)-induced regression of the rat corpus luteum. Here we have compared the ability of prostaglandin F2alpha (PGF) and PRL to induce, in rat corpora lutea, inflammatory events thought to perpetuate luteal regression. Immature rats were ovulated with eCG-hCG and then hypophysectomized (Day 0), which resulted in a single cohort of persistent, functional corpora lutea. On Days 9-11, the rats received twice daily injections of saline, PGF (Lutalyse, 250 microg/injection), or PRL (312 microg/injection) to induce luteal regression. Surprisingly, luteal weight and plasma progestin concentrations (progesterone and 20alpha-dihydroprogesterone) did not differ between PGF-treated rats and controls; whereas both luteal weight and plasma progestins declined significantly in PRL-treated rats. Furthermore, corpora lutea of PGF-treated rats and controls contained relatively minimal ICAM 1 staining and few monocytes/macrophages. In contrast, but as expected, corpora lutea of PRL-treated rats stained intensely for ICAM-1 and contained numerous monocytes/macrophages. In an additional experiment, there was no indication that luteal prostaglandin F2alpha receptor mRNA diminished as a result of hypophysectomy. These findings suggest that prolactin, not PGF, induces the inflammatory events that accompany regression of the rat corpus luteum. PMID- 11207206 TI - Internalization rates of murine and ovine gonadotropin-releasing hormone receptors. AB - Rates of internalization of the murine GnRH receptor fused via its C-terminus to green fluorescent protein (GnRH-R-GFP) were examined in Chinese hamster ovary cells (CHO cells) and compared to those of native murine GnRH-R in a clonal murine gonadotroph cell line (LbetaT2 cells). The resulting rates of internalization of murine receptors were then compared with those of sheep GnRH-R in ovine gonadotrophs. Cells were incubated with radioiodinated [D-Ala6]GnRH on ice for 4 h to allow binding of the ligand to GnRH-R, then cells were warmed to 37 degrees C to permit internalization. Surface-bound radioligand began to decrease as soon as the cells were warmed and had decreased significantly within 20 min. A steady-state level of surface-bound radioligand was achieved after 60 min in both CHO cells and LbetaT2 cells (38% and 41%, respectively, of initial value; P < 0.05). Internalization of radioligand began immediately after warming the cells to 37 degrees C, and a significant proportion of surface ligand had been internalized by 20 min. A steady-state maximum of internalization was reached after 60 min in both CHO cells and LbetaT2 cells (29% and 28%, respectively, of total cell-associated ligand; P < 0.05). Changes in surface bound radioligand and internalized radioligand in sheep pituitary cells were similar to those in CHO cells and LbetaT2 cells, but the amount of radioligand internalized after 60 min (40% of total cell-associated ligand) was 1.4 times higher than in CHO cells and LbetaT2 cells (P < 0.05). In a separate experiment, the effect of estradiol on the rate of internalization of GnRH-R in ovine pituitary cells was examined. Although treatment of ovine pituitary cells with estradiol approximately doubled the number of GnRH receptors, it did not alter either the rate or extent of receptor internalization. These results show that rates of internalization of recombinant murine GnRH-R-GFP in CHO cells and native murine and ovine GnRH-R in LbetaT2 cells and in sheep pituitary cells, respectively, are similar, but amounts of ovine GnRH-R internalized are greater than those for murine GnRH-R. Further, the rate of internalization of occupied receptor is similar in gonadotroph and nongonadotroph cells, and the addition of GFP to the C-terminus of the murine GnRH-R does not alter the rate of internalization. PMID- 11207207 TI - Mitochondrial distribution and adenosine triphosphate content of bovine oocytes before and after in vitro maturation: correlation with morphological criteria and developmental capacity after in vitro fertilization and culture. AB - In this study, we evaluated mitochondrial distribution and ATP content of individual bovine oocytes before and after in vitro maturation (IVM). Cumulus oocyte complexes were classified according to morphological criteria: category 1, homogeneous oocyte cytoplasm, compact multilayered cumulus oophorus; category 2, cytoplasm with small inhomogeneous areas, more than five layers of compact cumulus; category 3, heterogeneous/vacuolated cytoplasm, three to five layers of cumulus including small areas of denuded zona pellucida; category 4, heterogeneous cytoplasm, completely or in great part denuded. In immature oocytes, staining with MitoTracker green revealed mitochondrial clumps in the periphery of the cytoplasm, with a strong homogenous signal in category 1 oocytes, a weaker staining in category 2 oocytes, allocation of mitochondria around vacuoles in category 3 oocytes, and poor staining of mitochondria in category 4 oocytes. After IVM, mitochondrial clumps were allocated more toward the center, became larger, and stained more intensive in category 1 and 2 oocytes. This was also true for category 3 oocytes; however, mitochondria maintained their perivacuolar distribution. No mitochondrial reorganization was seen for category 4 oocytes. Before IVM, the average ATP content of category 1 oocytes (1.8 pmol) tended to be higher than that of category 2 oocytes (1.6 pmol) and was significantly (P < 0.01) higher than in category 3 (1.4 pmol) and 4 oocytes (0.9 pmol). The IVM resulted in a significant (P < 0.01) increase in the average ATP content of all oocyte categories, with no difference between oocytes extruding versus nonextruding a polar body. After in vitro fertilization (IVF) and culture, significantly (P < 0.05) more category 1 and 2 than category 3 and 4 oocytes developed to the morula or blastocyst stage (determined 168 h after IVF). Total cell numbers of expanded blastocysts derived from category 1 and 2 oocytes were significantly (P < 0.05) higher than of those originating from category 3 and 4 oocytes. These data indicate that mitochondrial reorganization and ATP levels are different between morphologically good and poor oocytes and may be responsible for their different developmental capacity after IVF. PMID- 11207208 TI - A comparative study of gene expression in murine embryos developed in vivo, cultured in vitro, and cocultured with human oviductal cells using messenger ribonucleic acid differential display. AB - The objectives of this study were to compare the mRNA expression patterns in early mouse embryos in different culture conditions by differential display reverse transcription-polymerase chain reaction (DDRT-PCR). Embryos developed in vivo, cultured in vitro, and cocultured with human oviductal epithelial cells were studied at the 2-cell, 4-cell, 8-cell/morula, and blastocyst stages. Messenger RNA profiles were displayed by DDRT-PCR using downstream T11VV (V = A, C, or G) and upstream decamer primers. Total cDNA banding patterns were highly conserved in the three groups studied. Some fragments are unique in different culture conditions. Thirteen out of the 40 selected differentially expressed clones were characterized. The DNA sequence analyses of these clones displayed high sequence homology with cDNA sequences in the mouse expressed sequence tag database. Using semiquantitative RT-PCR, we confirmed differential expression of these DD amplicons in the three groups of embryos. The temporal expression of some of the selected DD amplicons during preimplantation development were studied in the three groups of embryos. In conclusion, DDRT-PCR is an effective tool for contrasting gene expression patterns and characterizing mRNA transcripts in mouse embryo. PMID- 11207210 TI - Diethylstilbestrol-treated adult rats with altered epididymal sperm numbers and sperm motility parameters, but without alterations in sperm production and sperm morphology. AB - In this study, we characterized estrogenic effects of diethylstilbestrol (DES) on reproductive parameters in male rats to identify a minimal dose level that alters epididymal and sperm functions but has little or no effect on sperm production and/or spermatogenesis. Adult rats (five animals/group) received s.c. injections of 0.2 ml of corn oil containing DES at a rate of 1.0 mg, 200 microg, 40 microg, 8 microg, 1.6 microg, or 320 ng x rat(-1) x day(-1) for 12 days. The control group received corn oil only. DES effects were similar in the 8-microg group and higher dose groups and included significant (P < or = 0.05) reductions in 1) absolute and relative weights of the head and body of the epididymis (EP), tail of the EP, and seminal vesicle, 2) numbers of sperm in both regions of the EP, and 3) motility characteristics in sperm collected from the tail of the EP. Conversely, no significant changes were observed in relative testis weight, daily sperm production, spermatogenesis, seminiferous epithelial height in stage VII, and sperm morphology. All of the above parameters in the 1.6-microg group (except seminal vesicle weight) and 320-ng group were comparable to those of controls. Plasma testosterone (T) level was reduced to an almost undetectable level in the > or = 8-microg groups and to a very low level in the 1.6-microg group (0.35 vs. 2.36 ng/ml in controls or 320-ng group), but LH level was unaltered. In a parallel fertility study, males received DES at a rate of 40, 8, or 1.6 microg x rat(-1) x day(-1) for 12 days prior to and 12 days during cohabitation (1:1) with untreated females. Of the 15 females cohabited with treated males (5 females/dose), none in the 40-microg and 8-microg groups and 1 in the 1.6-microg group formed a copulatory plug and delivered 8 pups, in contrast to 5/5 copulatory plugs and 13-15 pups/litter in the controls. DES at a rate of 8 microg x rat(-1) x day(-1) for 12 days reduced EP weights, sperm numbers in the EP, and sperm motility patterns but caused minimal to no alterations in daily sperm production, spermatogenesis, or sperm morphology. Factors other than T, or in addition to lower T, may be responsible for DES-induced reproductive disorders (despite lower T, sperm contents and sperm motility patterns in the EP were normal in the 1.6-microg group). Deficits in EP sperm functions and/or sexual behavior (as evident from absence of copulatory plugs) probably accounted for reduced fertility in treated males. PMID- 11207209 TI - Culture of preimplantation mouse embryos affects fetal development and the expression of imprinted genes. AB - Culture of preimplantation mammalian embryos and cells can influence their subsequent growth and differentiation. Previously, we reported that culture of mouse embryonic stem cells is associated with deregulation of genomic imprinting and affects the potential for these cells to develop into normal fetuses. The purpose of our current study was to determine whether culture of preimplantation mouse embryos in a chemically defined medium (M16) with or without fetal calf serum (FCS) can affect their subsequent development and imprinted gene expression. Only one third of the blastocysts that had been cultured from two cell embryos in M16 medium complemented with FCS developed into viable Day 14 fetuses after transfer into recipients. These M16 + FCS fetuses were reduced in weight as compared with controls and M16 fetuses and had decreased expression of the imprinted H19 and insulin-like growth factor 2 genes associated with a gain of DNA methylation at an imprinting control region upstream of H19. They also displayed increased expression of the imprinted gene Grb10. The growth factor receptor binding gene Grb7, in contrast, was strongly reduced in its expression in most of the M16 + FCS fetuses. No alterations were detected for the imprinted gene MEST: Preimplantation culture in the presence of serum can influence the regulation of multiple growth-related imprinted genes, thus leading to aberrant fetal growth and development. PMID- 11207211 TI - Identification, cloning, and initial characterization of a novel mouse testicular germ cell-specific antigen. AB - A monoclonal antibody, designated TES101, was raised by immunizing BALB/c mice with an allogenic mouse testicular homogenate followed by immunohistochemical selection as the initial screening method. By searching the expressed sequence tag (EST) database with the N-terminal amino acid sequence of TES101 reactive protein, we found that the predicted amino acid sequence encoded by a mouse testicular EST clone matched the TES101 protein sequence. Sequence analysis of the clone revealed no homologous molecule in the DNA/protein database. Based on data obtained from N-terminal amino acid analysis of the TES101 protein, the derived amino acid sequence contained a signal peptide region of 25 amino acids and a mature protein region of 225 amino acids, which translated into a protein with a molecular weight of 24 093. Northern blot analysis showed that mRNA of the TES101 protein was found in testis but not in any other mouse tissues examined. Western blot analysis revealed that TES101 reacted with a 38-kDa band on SDS-PAGE under nonreducing conditions, and this reactivity was abrogated under reducing conditions. Immunoelectron microscopic studies demonstrated that the molecule was predominantly located on the plasma membrane of spermatocytes and spermatids but not in Sertoli cells or interstitial cells, including Leydig cells. Thus, the TES101 protein is a novel molecule present primarily on the surface of developing male germ cells. TES101 protein may play a role in the processes underlying male germ cell formation. PMID- 11207212 TI - Expression of Fas and Fas ligand in normal and ischemia-reperfusion testes: involvement of the Fas system in the induction of germ cell apoptosis in the damaged mouse testis. AB - Apoptosis of germ cells is very common in normal and injured mammalian testes. The aim of this study was to examine the possible involvement of the Fas and Fas ligand (FasL) system in the induction of germ cell apoptosis in normal and ischemia-reperfusion testes of adult mice. Apoptosis was assessed by the TUNEL method and by DNA gel electrophoresis. Fas and FasL mRNAs were detected by Northern blotting and reverse transcription polymerase chain reaction techniques, and proteins were analyzed by Western blotting and immunohistochemistry. Apoptosis of germ cells was identified in the normal testis especially around stages XI and XII, whereas the expression of Fas and FasL was largely confined to Leydig cells and Sertoli cells, respectively. However, in the testes reperfused after 1 h of ischemia, a high number of TUNEL-positive cells were identified in parallel with increased Fas-positive germ cells, whereas FasL expression in Sertoli cells was almost constant irrespective of the duration of reperfusion. Moreover, i.p. injection of anti-Fas antibody, which blocks the interaction between Fas and FasL, inhibited apoptosis, as indicated by the reduced number of TUNEL-positive cells, except for apoptosis at stages XI and XII. Our results indicate that the Fas/FasL system mediates apoptosis of spermatogenic cells in the injured testis but not spontaneous apoptosis in the normal testis. PMID- 11207213 TI - Disruption of neuroendocrine control of luteinizing hormone secretion by aroclor 1254 involves inhibition of hypothalamic tryptophan hydroxylase activity. AB - Mechanisms governing the effect of polychlorinated biphenyl (PCB) toxicity on hypothalamic serotonergic function and the neuroendocrine system controlling LH secretion were investigated in Atlantic croaker (Micropogonias unulatus) exposed to the PCB mixture Aroclor 1254 (1 microg x g body weight(-1) x day(-1)) in the diet for 30 days. PCB treatment caused a decrease in hypothalamic 5 hydroxytryptamine (5-HT) concentrations and significant inhibition of hypothalamic tryptophan hydroxylase (TPH), the rate-limiting enzyme in 5-HT synthesis, but did not alter the activity of monoamine oxidase, the catabolic enzyme. Further, PCB treatment caused significant decreases in GnRH content in the preoptic-anterior hypothalamic area. Significant decreases in pituitary GnRH receptor concentrations and the LH response to the GnRH analogue (GnRHa) were also observed in PCB-exposed fish, possibly as a consequence of a decline in GnRH release. The possible association between impaired serotonergic and neuroendocrine functions after PCB treatment was explored using serotonergic drugs. Treatment of croaker with p-chlorophenylalanine, an irreversible TPH inhibitor, mimicked the effects of PCB on the GnRH system and the LH response to GnRHa. Bypassing the TPH-dependent hydroxylation step with the administration of 5-hydroxytryptophan restored 5-HT to control levels and prevented the deleterious effects of PCB on the neuroendocrine parameters. Moreover, slow-release GnRH implants prevented the PCB-induced decline in GnRH receptors and restored the LH response to GnRHa, suggesting that GnRH therapy can reverse PCB-induced disruption of LH secretion. These results demonstrate that TPH is one of the targets of PCB neurotoxicity and indicate that a decrease in 5-HT availability in PCB-exposed croaker results in disruption of the stimulatory 5-HT/GnRH pathway controlling LH secretion. PMID- 11207214 TI - Interferon-tau suppresses prostaglandin F2alpha secretion independently of the mitogen-activated protein kinase and nuclear factor kappa B pathways. AB - Pregnancy is established in ruminants through inhibitory actions of interferon (IFN)-tau on the release of prostaglandin F2alpha (PGF), which allows the corpus luteum to survive and continue to produce progesterone. Experiments were designed to 1) delineate the signal transduction pathway coordinating the synthesis of PGF, 2) determine how rapidly recombinant bovine (rb) IFN-tau attenuated phorbol ester (PDBu)-induced secretion of PGF, and 3) establish the site at which rbIFN tau attenuates the secretion of PGF in cultured bovine endometrial (BEND) cells. BEND cells were untreated (control) or treated for 5, 10, 60, 180, or 300 min with PDBu (100 ng/ml), rbIFN-tau (50 or 500 ng/ml), PDBu + rbIFN-tau, or PDBu + PD98059 (MEK-1 inhibitor; 50 microM). Secretion of PGF was induced (P < 0.0001) by PDBu within 180 min, but induction was inhibited 74% by the addition of rbIFN tau (P < 0.0001) and was ablated completely by PD98059. Parallel results were obtained for cyclooxygenase (COX)-2 protein expression. PDBu induced (P < 0.05) activation of the Raf-1/MEK-1/ERK-1/2 pathway, which was obligatory for the expression of COX-2 and secretion of PGF but was not altered by cotreatment with rbIFN-tau. PDBu induced (P < 0.05) transcription of c-jun and c-fos mRNAs within 30 min; induction was inhibited (P < 0.05) by cotreatment with PD98059 but not by cotreatment with rbIFN-tau. Treatment of BEND cells with rbIFN-tau also did not attenuate PDBu-induced degradation of IkappaBalpha, suggesting that the IkappaBalpha/NFkappaB pathway is not a site of IFN-tau inhibition of PGF. However, rbIFN-tau did block transcription of the COX-2 gene induced by PDBu within 30 min. In conclusion, COX-2 expression and PGF secretion induced by PDBu is mediated through the Raf-1/MEK-1/ERK-1/2 pathway, but this pathway is not disrupted by rbIFN-tau. Because rbIFN-tau inhibits COX-2 mRNA within 30 min, we hypothesized that transcription factors activated by rbIFN-tau rapidly and directly attenuate COX-2 gene expression, thereby suppressing secretion of PGF. PMID- 11207215 TI - Aging-related expression of inducible nitric oxide synthase and markers of tissue damage in the rat penis. AB - Erectile dysfunction in the aging male results in part from the loss of compliance of the corpora cavernosal smooth muscle due to the progressive replacement of smooth muscle cells by collagen fibers. We have examined the hypothesis that a spontaneous local induction of inducible nitric oxide synthase (iNOS) expression and the subsequent peroxynitrite formation occurs in the penis during aging and that this process is accompanied by a stimulation of smooth muscle apoptosis and collagen deposition. The penile shaft and crura were excised from young (3-5 mo old) and old (24-30 mo old) rats, with or without perfusion with 4% formalin. Fresh tissue was used for iNOS and proteasome 2C mRNA determinations by reverse transcription polymerase chain reaction assay, ubiquitin mRNA by Northern blot, and iNOS protein by Western blot. Penile sections from perfused animals were embedded in paraffin and immunostained with antibodies against iNOS and nitrotyrosine, submitted to the TUNEL assay for apoptosis, or stained for collagen, followed by image analysis quantitation. A 4.1-fold increase in iNOS mRNA was observed in the old versus young tissues, paralleled by a 4.9-fold increase in iNOS protein. The proteolysis marker, ubiquitin, was increased 1.9-fold, whereas a related gene, proteasome 2c, was not significantly affected. iNOS immunostaining was increased 3.6-fold in the penile smooth muscle of the old rats as compared with the young rats. The peroxynitrite indicator nitrotyrosine was increased by 1.6-fold, accompanied by a 3.6-fold increase in apoptotic cells and a 2.0-fold increase in collagen fibers in the old penis. In conclusion, aging in the penis is accompanied by an induction of iNOS and peroxynitrite formation that may lead to the observed increase in apoptosis and proteolysis and may counteract a higher rate of collagen deposition in the old penis. PMID- 11207216 TI - Molecular characterization of bovine prostaglandin G/H synthase-2 and regulation in uterine stromal cells. AB - Prostaglandin G/H synthase (PGHS) is a key rate-limiting enzyme in the prostaglandin biosynthetic pathway, and prostaglandins play a central role in the control of the reproductive cycle. The objectives of this study were to clone and characterize the primary structure of bovine PGHS-2 and to study its regulation in uterine stromal cells in vitro. The bovine PGHS-2 cDNA was cloned by a combination of reverse transcription-polymerase chain reaction and cDNA library screening. Results showed that the complete bovine PGHS-2 cDNA is composed of a 5'-untranslated region of 128 bp, an open reading frame of 1815 bp, and a 3' untranslated region of 1565 bp containing multiple repeats (n = 11) of the Shaw Kamen sequence 5'-ATTTA-3'. The open reading frame encodes a 604-amino acid protein that is 86-97% identical to other mammalian PGHS-2 homologs. The regulation of PGHS-2 mRNA and protein was studied in primary cultures of bovine uterine stromal cells stimulated with phorbol 12-myristate 13-acetate (PMA; 100 nM). Northern and Western blot analyses reveal a marked induction in PGHS-2 transcript (4.0 kilobases) and protein (M(r) = 72 000) after 3-12 h of PMA stimulation (P < 0.05). However, this induction was transient in nature as levels of PGHS-2 mRNA and protein returned to basal levels after 24 h of PMA stimulation. In contrast, PMA had no effect on levels of PGHS-1 (P > 0.05). The PMA-dependent induction of PGHS-2 was associated with a significant increase in prostaglandin E2 secretion in the culture media (P < 0.05). To study promoter activity of the 5'-flanking DNA region of the bovine PGHS-2 gene, the genomic fragment -1574/-2 (+1 = transcription start site), as well as a series of 5' deletion mutants, were fused upstream of the firefly luciferase gene and transiently transfected into primary cultures of bovine uterine stromal cells. Results showed that a first promoter region located between -1574 and -492 and a second region between -88 and -39 appear to play important roles in PMA-dependent regulation of PGHS-2 promoter activity in bovine uterine cells. Thus, this study characterizes for the first time the structure of the bovine PGHS-2 transcript and the deduced amino acid sequence of its encoded protein and establishes an in vitro model to study the regulation of PGHS-2 gene expression in bovine uterine tissue. PMID- 11207217 TI - Monocyte chemotactic protein-1 and -2 messenger ribonucleic acids in the ovine uterus: regulation by pregnancy, progesterone, and interferon-tau. AB - Endometrial leukocytes may play important roles during pregnancy. Because chemokines are regulators of immune cell activity and trafficking, this study determined if mRNAs for monocyte chemotactic proteins (MCP) were present in the ovine uterus and regulated by progesterone (P) and/or recombinant ovine interferon tau (roIFN-tau). Uteri of normal cycling and pregnant ewes (experiment 1) and uteri of ovariectomized ewes receiving intrauterine infusions of IFN-tau and/or i.m. injections of P (experiment 2) were used to detect MCP-1 and MCP-2 mRNA. In experiment 1, slot-blot hybridization analysis of endometrial total RNA revealed that MCP-1 and MCP-2 mRNA levels did not change during the estrous cycle but increased between Days 13 and 19 of pregnancy. Using in situ hybridization, MCP-1 and MCP-2 mRNA were localized to immune cells in the subepithelial compact stroma. Histomorphological studies and in situ hybridization for major basic protein (MBP) indicated that MCP-positive immune cells were eosinophils. In experiment 2, treatment with P and roIFN-tau increased (P < 0.05) the number of MCP-1- and MCP-2-expressing eosinophils in the endometrium compared to ewes treated with P alone. Injection of the P receptor antagonist (ZK 137,316) inhibited effects of P and/or roIFN-tau to recruit eosinophils expressing MCP-1 and MCP-2 mRNAs. Endometrial production of MCPs by eosinophils during early pregnancy may play a role(s) in central implantation and/or placentation in ewes that is crucial for successful establishment of pregnancy. PMID- 11207218 TI - Differential expression of the coxsackievirus and adenovirus receptor regulates adenovirus infection of the placenta. AB - The molecular mechanisms and pathologic significance of placental viral infections are poorly understood. We investigated factors that regulate placental infection by adenovirus, which is the most common viral pathogen identified in fetal samples from abnormal pregnancies (i.e., fetal growth restriction, oligohydramnios, and nonimmune fetal hydrops). We also determined the pathologic significance of placental adenovirus infection. Northern hybridization, flow cytometry, and immunostaining revealed that placental expression of the coxsackievirus and adenovirus receptor (CAR) varied with gestational age and trophoblast phenotype. The CAR was continuously expressed in invasive or extravillous trophoblast cells but not in villous trophoblast cells. We postulate that the villous syncytiotrophoblast, which does not express CAR and is resistant to adenovirus infection, limits the transplacental transmission of viral pathogens, including adenovirus. Conversely, extravillous trophoblast cells underwent apoptosis when infected by adenovirus in the presence of decidual lymphocytes (which simulated the maternal immune response to viral infection). Thus, adenovirus infection and/or the maternal immune response to adenovirus infection induced the death of placental cell types that expressed CAR. Consequently, we speculate that adenovirus infection of extra-villous trophoblast cells may negatively impact the process of placental invasion and predispose the mother and fetus to adverse reproductive outcomes that result from placental dysfunction. PMID- 11207219 TI - Molecular biology of channel catfish gonadotropin receptors: 1. Cloning of a functional luteinizing hormone receptor and preovulatory induction of gene expression. AB - There is little known about the molecular biology of piscine gonadotropin receptors, and information about gene expression during reproductive development is particularly lacking. We have cloned the LH receptor (LHR) in the channel catfish (cc), and examined its gene expression throughout a reproductive cycle. A cDNA encoding the receptor was isolated from the testis using reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends procedures. It encoded a 696-amino acid protein that showed the greatest homology (46-50% identity) with the known LHRs and lesser similarity with FSH receptors and thyroid-stimulating hormone receptors (44-47% and 42-44% identity, respectively). In addition, two characteristics unique to the LHRs were conserved in the cloned receptor and the encoding gene: presence of an intron corresponding to intron 10 in mammals and turkey and occurrence of a double cysteine residue in the cytoplasmic tail for potential palmitoylation. The ccLHR gene was well expressed in the gonads and kidney and merely detectable in the gills, muscle, and spleen. The isolated cDNA encoded an active ccLHR protein, as the recombinant receptor expressed in COS7 cells activated a cAMP response element-driven reporter gene (luciferase) upon exposure to hCG in a dose-dependent manner. Seasonal changes in the ovarian expression of the ccLHR gene, as examined by measuring the transcript abundance by quantitative real-time RT-PCR, remained rather low during most of the reproductive cycle but was acutely induced around the time of spawning. This pattern of expression correlates well with the reported expression of its ligand (LH) in fishes and concurs with the notion that LH is a key regulator of the periovulatory maturational events. PMID- 11207220 TI - Evidence of selection bias in preterm survival studies: a systematic review. AB - OBJECTIVE: To determine by how much selection bias in preterm infant cohort studies results in an overestimate of survival. DESIGN: Systematic review of studies reporting survival in infants less than 28 weeks of gestation published 1978-1998. Studies were graded according to cohort definition: A, stillbirths and live births; B, live births; C, neonatal unit admissions. Proportions of infants surviving to discharge were calculated for each week of gestation. RESULTS: Sixty seven studies report data on 55 cohorts (16 grade A, 23 grade B, 16 grade C). Studies that are more selective report significantly higher survival between 23 and 26 weeks of gestation (grade C > grade B > grade A, p < 0.01), exaggerating survival by 100% and 56% at 23 and 24 weeks respectively. CONCLUSION: To minimise the potential for overestimating survival around the limits of viability, future studies should endeavour to report the outcome of all pregnancies for each week of gestation (terminations, miscarriages, stillbirths, and all live births). PMID- 11207221 TI - Neonatal meningitis in England and Wales: 10 years on. AB - OBJECTIVES: To determine the incidence of neonatal meningitis in England and Wales. DESIGN: A national postal survey using the British Paediatric Surveillance Unit (BPSU) card scheme supplemented by information from other sources. SETTING: England and Wales 1996-1997. SUBJECTS: A total of 274 babies less than 28 days of age who were treated for meningitis. RESULTS: The incidence of neonatal meningitis in England and Wales has not changed since our previous study in 1985 1987. However, the acute phase mortality has fallen from 19.8% in 1985-1987 to 6.6% in this study. Group B streptococci (42%) and Escherichia coli (16%) remain the most common infecting microorganisms. Eight of 69 (12%) babies with group B streptococci and 4/26 (15%) with E coli died. Antibiotic regimens based on the third generation cephalosporins, notably cefotaxime, were most commonly used (84%). The BPSU scheme identified 72% of cases during the study period. Most cases of viral meningitis were not reported through the BPSU. Less than a third of samples from aseptic meningitis were examined for viruses; 56% of these were positive. CONCLUSIONS: Although the incidence of neonatal meningitis remains unchanged, mortality from this infection has fallen significantly. If this improvement is maintained as reflected in the level of sequelae at 5 years of age, then the fear surrounding meningitis during the neonatal period will have been dramatically reduced. PMID- 11207222 TI - Brain specific proteins in posthaemorrhagic ventricular dilatation. AB - Median neurofilament and glial fibrillary acidic protein concentrations in the cerebrospinal fluid of 18 infants with posthaemorrhagic ventricular dilatation were 20-200 times higher than control values. S-100 protein in cerebrospinal fluid was four times higher than control values. Glial fibrillary acidic protein concentrations correlated with death or disability and with parenchymal lesions but not with shunt dependence. PMID- 11207223 TI - Neonatal cranial ultrasound interpretation: a clinical audit. AB - OBJECTIVE: To assess the abilities of doctors to interpret neonatal cranial ultrasound scans. DESIGN AND SETTING: High resolution scanned images of six important neonatal cranial ultrasound abnormalities were posted as a questionnaire to the 59 neonatal units in the North and South Thames regions. RESULTS: Forty two questionnaires were returned (71%). Currently 56% of those interpreting cranial ultrasound scans are neonatal registrars, 27% are consultant paediatricians or neonatologists, and 17% are radiologists. The response rate from registrars was excellent (97%), but it was poor from consultant paediatric (38%) and radiological (40%) staff. The mean accurate identification of cerebral abnormalities was only 59% (range 45-71%). Only 44% of the neonatal registrars, compared with nearly all the consultant staff, have had any formal training in cranial ultrasonography. CONCLUSIONS: The data highlight the current accuracy of neonatal cranial ultrasound scan reporting in the Greater London region and have important implications for clinical services and research studies. Doctors who are responsible for interpreting neonatal cranial ultrasound scans should have formal training and supervision, and more formal reporting would improve and maintain standards. The findings raise significant doubts about the accuracy of local interpretation of cranial ultrasound scans in multicentre research studies. PMID- 11207224 TI - Red blood cell transfusions in very and extremely low birthweight infants under restrictive transfusion guidelines: is exogenous erythropoietin necessary? AB - OBJECTIVE: To examine the number and volume of red blood cell transfusions (RBCTs) in very and extremely low birthweight infants under restrictive red blood cell transfusion guidelines without erythropoietin administration, and to compare the results with those reported in similar infants receiving erythropoietin. METHODS: From April 1996 to June 1999, all RBCTs given to infants with a birth weight of less than 1500 g were prospectively recorded. Data on RBCT combined with erythropoietin treatment and RBCT guidelines were extracted from four prospective randomised trials of erythropoietin for anaemia of prematurity. RESULTS: When the restrictive RBCT guidelines were followed, the number of RBCTs and volume transfused were similar to those reported during erythropoietin administration. CONCLUSIONS: RBCT guidelines may have a similar impact on RBCT in very low birthweight infants to the administration of erythropoietin. The effect of RBCT guidelines on RBCT frequency should be considered when evaluating the efficacy of erythropoietin administration to preterm infants. PMID- 11207225 TI - Hepatic iron storage in very low birthweight infants after multiple blood transfusions. AB - OBJECTIVE: To investigate the effect of multiple blood transfusions on hepatic iron storage in preterm, very low birthweight (VLBW) infants. METHODS: Seventeen VLBW infants who died within the first six months of life and underwent postmortem examination were studied. Serum ferritin, iron, and total iron binding capacity were measured within the week before the infants' death. Liver iron concentration was quantitatively determined by atomic absorption spectrophotometry and semiquantitatively assessed by histochemical liver iron grading. The clinical characteristics and the iron results were compared between infants receiving < 100 ml of blood (group A) and those receiving >/= 100 ml (group B). Spearman's correlation coefficient was used to evaluate the relation between the volume of blood transfused and serum/liver iron concentrations. Statistically significant variables associated with liver iron concentration were further subjected to multivariate stepwise regression analysis. RESULTS: Infants in group B had significantly higher serum iron (p < 0.01), serum ferritin (p < 0.01), and liver iron concentration (p < 0.01) than those in group A. The total and net volume of blood transfused were significantly associated with liver iron concentration (p < 0.001, r = 0.86; p < 0.001, r = 0.71 respectively), semiquantitative histochemical liver iron grading (p < 0.001, r = 0.80; p < 0.005, r = 0.71 respectively), and serum ferritin (p < 0.001, r = 0.84; p < 0.01, r = 0.69 respectively). In addition, both liver iron concentration and liver iron grading were found to be significantly associated with serum ferritin (p < 0.001, r = 0.76; p < 0.005, r = 0.68 respectively). Multivariate stepwise regression analysis indicated that the (log) liver iron concentration was significantly associated with the (log) volume of blood transfusion (p < 0.001; regression coefficient 0.39, SE 0.09), after adjustment for gestational age (R(2) = 0.84). CONCLUSIONS: This study showed a significant positive relation between the volume of blood transfused and the liver iron concentration in preterm VLBW infants. Although the transfusional blood volume correlated closely with the amount of iron deposited in hepatic tissues, clinical manifestations of iron overload were not observed. Carers should be aware of this potential harmful effect before prescribing blood or routine iron supplement to vulnerable preterm infants. PMID- 11207226 TI - Pulse oximetry, severe retinopathy, and outcome at one year in babies of less than 28 weeks gestation. AB - AIM: To determine whether differing policies with regard to the control of oxygen saturation have any impact on the number of babies who develop retinopathy of prematurity and the number surviving with or without signs of cerebral palsy at one year. METHODS: An examination of the case notes of all the 295 babies who survived infancy after delivery before 28 weeks gestation in the north of England in 1990-1994. RESULTS: Babies given enough supplemental oxygen to maintain an oxygen saturation of 88-98%, as measured by pulse oximetry, for at least the first 8 weeks of life developed retinopathy of prematurity severe enough to be treated with cryotherapy four times as often as babies only given enough oxygen to maintain an oxygen saturation of 70-90% (27.2% v 6.2%). Surviving babies were also ventilated longer (31.4 v 13.9 days), more likely to be in oxygen at a postmenstrual age of 36 weeks (46% v 18 %), and more likely to have a weight below the third centile at discharge (45% v 17%). There was no difference in the proportion who survived infancy (53% v 52%) or who later developed cerebral palsy (17% v 15%). The lowest incidence of retinopathy in the study was associated with a policy that made little use of arterial lines. CONCLUSIONS: Attempts to keep oxygen saturation at a normal "physiological" level may do more harm than good in babies of less than 28 weeks gestation. PMID- 11207227 TI - Cerebral palsy in the surviving twin associated with infant death of the co-twin. AB - BACKGROUND: Monozygotic twins are at greater risk of dying and of serious morbidity than dizygotic twins, and both are at greater risk than singletons. This is only partly explained by the higher proportion of low birthweight infants among twins. AIM: To compare, in same sex and different sex twins, birth weight specific neonatal death rates and cerebral palsy prevalence rates in the surviving twin when the co-twin has died in infancy. METHODS: Analysis of birth and death registration data for same sex and different sex twins for England and Wales 1993-1995 where both were live births. Death certificates of all liveborn twins who died were obtained from the Office for National Statistics. A questionnaire was sent to the general practitioners of all surviving co-twins to determine if the child had any disability. RESULTS: The neonatal death rate in same sex twins was 25.4 and in different sex twins 18.0 per 1000 live births (death rate difference 7.4; 95% confidence interval 4.7 to 10.1; p < 0.001). The higher neonatal death rate in same sex compared with different sex twins is attributable to the higher proportion of same sex twins with low birth weight. Prevalence of cerebral palsy in the low birthweight group (< 1000 g) was marginally higher in same sex (224 per 1000) than different sex (200 per 1000) twin survivors. In the birth weight group 1000-1999 g, same sex twin survivors were at a significantly higher risk of cerebral palsy than those of different sex: 167 v 21 per 1000; difference 145 (95% confidence interval 44 to 231; p < 0.01) per 1000 infant survivors. CONCLUSION: There are two components to the cause of cerebral palsy in twins. Immaturity per se predisposes to cerebral damage. Also, same sex twins may sustain cerebral damage that is in excess of that due to immaturity. PMID- 11207228 TI - Respiratory distress syndrome and birth order in premature twins. AB - OBJECTIVE: To determine the effect of birth order on respiratory distress syndrome (RDS) in the outcome of twins in a large premature population managed in a modern neonatal intensive care unit. METHODS: An historical cohort study design was used to analyse the neonatal outcomes of 301 premature liveborn twin sibling pairs of between 23 and 31 weeks gestation from the Australia and New Zealand Neonatal Network 1995 database. RESULTS: Among the 56 twin sibling pairs who were discordant for RDS, the second twin was affected in 41 cases (odds ratio (OR) 2.7, 95% confidence interval (CI) 1.5 to 5.3). The excess risk of RDS in the second twin increased with gestation and was statistically significant for twins above 29 weeks gestation (OR 4.4, 95% CI 1.6 to 15). CONCLUSIONS: There is a significant increased risk of RDS associated with being the second born of premature twins, which appears to depend on gestation. PMID- 11207229 TI - Refractory hypotension in preterm infants with adrenocortical insufficiency. AB - Five preterm, very low birthweight infants with severe hypotension and adrenocortical insufficiency are described. The profound hypotension was resistant to volume expansion and inotrope treatment, but responded promptly to corticosteroid treatment. A human corticotrophin releasing hormone (hCRH) test performed before corticosteroid treatment showed adequate pituitary response, and the endocrine dysfunction was identified at the adrenal level. Corticosteroid treatment should be considered and could be life saving in severely hypotensive preterm infants who do not respond to conventional treatment with volume expanders and inotropes. PMID- 11207231 TI - Positioning long lines: contrast versus plain radiography. AB - AIM: To assess the value of contrast versus plain radiography in determining radio-opaque long line tip position in neonates. METHODS: In a prospective study, plain radiography was performed after insertion of radio-opaque long lines. If the line tip was not visible on the plain film, a second film with contrast was obtained in an attempt to visualise the tip. RESULTS: Sixty eight lines were inserted during the study period, 62 of which were included in the study. In 31, a second radiographic examination with contrast was necessary to determine position of the tip. In 29 of these, the line tip was clearly visualised with contrast. On two occasions, the line tip could not be seen because the contrast had filled the vein and obscured the tip from view. Eight of the lines that required a second radiograph with contrast were repositioned. CONCLUSION: Intravenous contrast should be routinely used in the assessment of long line position in the neonate. PMID- 11207230 TI - Follow up care of bereaved parents after treatment withdrawal from newborns. AB - OBJECTIVE: To explore parents' experiences of bereavement care after withdrawal of newborn intensive care. DESIGN: Face to face interviews with 108 parents of 62 babies born over two calendar years in the East of Scotland. RESULTS: Only 22% were seen by six weeks after the death, 10% were not recalled before 6-11 months, and 8% were not seen at all in the first year. All except one couple saw the neonatologist who had cared for their baby. Only 33% remembered a neonatal nurse being present. Most (88%) were seen in the study hospital. Parents highlighted a number of specific needs. Appointments should be: (a) scheduled soon after the death of the baby and certainly within two months of the death irrespective of whether or not autopsy results are available; (b) with the named neonatologist; (c) in a setting away from the hospital if possible. Parents value: (a) efforts to find out how they are coping; (b) full frank information given sensitively to enable them to build up a cohesive picture of what happened and assess their future risks; (c) reassurance where possible, but half truths, false reassurances, and broken promises are unacceptable. CONCLUSIONS: Follow up care is a crucial part of the management of families from whose babies treatment has been withdrawn. Resources devoted to it should be re-examined to provide a service more in tune with parental need. In choosing the place, timing, and conduct of the meeting, staff should be sensitive to the expressed wishes of the parents themselves. PMID- 11207232 TI - Amphotericin B lipid complex for neonatal invasive candidiasis. AB - This study describes the safety and efficacy of amphotericin B lipid complex (ABLC) in 11 neonates with systemic Candida infections. Nine of the 11 improved clinically, and eight of nine evaluable patients had a mycological cure with ABLC. Creatinine levels improved or did not significantly change in eight of the 11 patients. PMID- 11207233 TI - Neonatal paroxetine withdrawal syndrome. AB - Four term neonates presented with symptoms such as jitteriness and necrotising enterocolitis after paroxetine exposure in utero. PMID- 11207234 TI - Preterm infants with athetoid cerebral palsy: kernicterus? PMID- 11207235 TI - Wilhelm Conrad Roentgen (1845-1923), the discovery of x rays and perinatal diagnosis. PMID- 11207236 TI - Dexamethasone treatment and cerebral palsy. PMID- 11207237 TI - Cutting edge: is vasoactive intestinal peptide a type 2 cytokine? AB - A component of the chemical language shared by the immune and nervous system is the expression of neuropeptides by immune cells. Vasoactive intestinal peptide (VIP) was shown to be produced by T lymphocytes. Here we investigate whether T cell subsets differentially express VIP. Our studies indicate that, upon specific Ag stimulation, Th2 and T2 cells, but not Th1 and T1 cells derived from TCR transgenic (Tg) mice, express VIP mRNA and protein, and secrete VIP. Following immunization with the specific Ag, significant levels of VIP are present in the serum of syngeneic, non-Tg hosts that receive Th2, but not Th1 Tg cells. Th2 Tg cells recovered from the non-Tg hosts immunized with the specific Ag, but not with an irrelevant Ag, express intracellular VIP. Because VIP is produced by Ag stimulated type 2 T cells, and differentially affects Th1 and Th2 cells, could VIP be viewed as a type 2 cytokine? PMID- 11207238 TI - Cutting edge: reversal of murine lupus nephritis with CTLA4Ig and cyclophosphamide. AB - Cyclophosphamide (CTX) prevents progression of nephritis and prolongs survival in (NZB x NZW)F(1) (B/W) mice and is used to treat humans with lupus nephritis. To compare the efficacy of CTLA4Ig with CTX and determine whether there is an incremental benefit to combining CTLA4Ig with CTX, we treated B/W mice with CTX, CTLA4Ig, or both agents. In mice with mild renal disease, treatment delayed the onset of proteinuria and prolonged survival in all groups. In mice with advanced renal disease, treatment with both agents reduced proteinuria in 71% of mice, whereas mice treated with either agent alone had no such improvement. Survival was also markedly improved among mice treated with both agents. Thus, combination treatment with CTX and CTLA4Ig is more effective than either agent alone in reducing renal disease and prolonging survival of B/W mice with advanced nephritis. This striking reversal of proteinuria is unprecedented in animal models of SLE. PMID- 11207239 TI - Cutting edge: the class II transactivator prevents activation-induced cell death by inhibiting Fas ligand gene expression. AB - The Fas:Fas ligand pathway is critical in regulating immune homeostasis by eliminating activated T cells that proliferated in response to an infection. Here, we show that the MHC class II transactivator (CIITA) can suppress this pathway by inhibiting transcription of the Fas ligand gene. CIITA can effectively repress transcription from the Fas ligand promoter in both T cell lines as well as primary cells. The repression appears to be at least partly due to interference of NFAT-mediated induction of Fas ligand gene transcription. T cells that express CIITA constitutively do not up-regulate Fas ligand on the cell surface after activation via the TCR. Consequently, these cells lack the ability to undergo activation-induced cell death, and to kill Fas-bearing target cells. PMID- 11207240 TI - Gastrointestinal cells of IL-7 receptor null mice exhibit increased sensitivity to irradiation. AB - IL-7 is a critical cytokine in the development of T and B cells but little is known about its activity on nonhematopoietic cells. An unexpected finding was noted in allogeneic bone marrow transplant studies using IL-7 receptor null (IL 7R alpha(-/-)) mice as recipients. These mice exhibited a significantly greater weight loss after total body irradiation compared with wild type, IL-7R alpha(+/+), mice. Pathological assessment indicated greater intestinal crypt damage in IL-7R alpha(-/-) recipients, suggesting these mice may be predisposed to gut destruction. Therefore, we determined the effect of the conditioning itself on the intestinal tract of these mice. IL-7R alpha(-/-) mice and IL-7R alpha(+/+) mice were irradiated and examined for lesions and apoptosis within the small intestine. In moribund animals, IL-7R alpha(-/-) mice had extensive damage in the small intestine, including marked ablation of the crypts and extreme shortening of villi following 1500 cGy total body irradiation. In contrast, by 8 days after irradiation, the small intestines of IL-7R alpha(+/+) mice had regenerated as distinguished by normal villus length and hyperplastic crypts. Following 750 cGy irradiation, IL-7R alpha(-/-) mice had a higher proportion of apoptotic cells in the crypts and an accompanying increase in the pro-apoptotic protein Bak was expressed in intestinal epithelial cells. These results demonstrate the increased radiosensitivity of intestinal stem cells within the crypts in IL-7R alpha(-/-) mice and a role for IL-7 in the protection of radiation-induced apoptosis in these same cells. This study describes a novel role of IL-7 in nonhematopoietic tissues. PMID- 11207241 TI - Human B cell growth and differentiation in the spleen of immunodeficient mice. AB - Human mAbs (HumAbs) have therapeutic potential against infectious diseases and cancer. Heretofore, their production has been hampered by ethical constraints preventing the isolation of Ag-specific activated B cells by in vivo immunization. Alternatively, severe combined immune deficient (SCID) mice, transplanted i.p. with human (Hu)-PBLs, allow the in vivo stimulation of human Ab responses without the usual constraints. Unfortunately, human B cells only represent a minor fraction of the surviving graft, they are scattered all over the animal body, and thus are hard to isolate for subsequent immortalization procedures. To prevent this dispersion and to provide the human B cells with a niche for expansion and maturation, SCID mice were engrafted with Hu-PBL directly into the spleen. Simultaneously endogenous murine NK cell activity was depleted by treatment with an anti-mouse IL-2 receptor beta-chain Ab. During engraftment, human B lymphocytes became activated, divided intensely, and differentiated into plasmacytoid cells. In vivo exposure to a recall Ag after cell transfer induced expansion of Ag-specific B cell clones. One week after inoculation, human B cells were abundant in the spleen and could easily be recovered for fusion with a heteromyeloma line. This resulted in the formation of stable hybridoma cell lines that secreted Ag-specific HumAbs. Thus transplantation of human lymphoid cells in the spleens of immune deficient mice represents a model for the study of human T cell-dependent B cell activation and proves to be an excellent tool for the successful production of HumAbs. PMID- 11207242 TI - Thioredoxin acts as a B cell growth factor in channel catfish. AB - To identify differentially expressed genes from channel catfish macrophages, a cDNA library from LPS-stimulated catfish macrophages was screened by subtractive hybridization. This screening yielded a 552-bp cDNA coding for catfish thioredoxin (CF-TRX). The deduced amino acid sequence revealed that CF-TRX contains 107 amino acids and is 59% homologous to human adult T cell leukemia derived factor/TRX, originally described as an IL-2R alpha-inducing factor. Northern blot analyses showed that CF-TRX is expressed in catfish T and macrophage cell lines, but weakly in B cell lines. Similar results were also observed in Western blot analyses using a mAb specific for recombinant CF-TRX (rTRX). The use of rTRX in functional studies demonstrated that rTRX induces in vitro proliferative responses of catfish PBL that were synergistically enhanced by the addition of culture supernatants from catfish T cell lines. In addition, cell separation studies and flow cytometric analyses revealed that the cells proliferating in rTRX-stimulated cultures were mostly B cells. These results suggest that CF-TRX may have an important role in the activation and proliferation of channel catfish B cells. PMID- 11207243 TI - The balance between CD45RChigh and CD45RClow CD4 T cells in rats is intrinsic to bone marrow-derived cells and is genetically controlled. AB - The level of CD45RC expression differentiates rat CD4 T cells in two subpopulations, CD45RC(high) and CD45RC(low), that have different cytokine profiles and functions. Interestingly, Lewis (LEW) and Brown Norway (BN) rats, two strains that differ in their ability to mount type 1 and type 2 immune responses and in their susceptibility to autoimmune diseases, exhibit distinct CD45RC(high)/CD45RC(low) CD4 T cell ratios. The CD45RC(high) subpopulation predominates in LEW rats, and the CD45RC(low) subpopulation in BN rats. In this study, we found that the antiinflammatory cytokines, IL-4, IL-10, and IL-13, are exclusively produced by the CD45RC(low) CD4 T cells. Using bone marrow chimeras, we showed that the difference in the CD45RC(high)/CD45RC(low) CD4 T cell ratio between naive LEW and BN rats is intrinsic to hemopoietic cells. Furthermore, a genome-wide search for loci controlling the balance between T cell subpopulations was conducted in a (LEW x BN) F(2) intercross. Genome scanning identified one quantitative trait locus on chromosome 9 (approximately 17 centiMorgan (cM); log of the odds ratio (LOD) score 3.9). In addition, two regions on chromosomes 10 (approximately 28 cM; LOD score 3.1) and 20 (approximately 40 cM; LOD ratio score 3) that contain, respectively, a cytokine gene cluster and the MHC region were suggestive for linkage. Interestingly, overlapping regions on these chromosomes have been implicated in the susceptibility to various immune-mediated disorders. The identification and functional characterization of genes in these regions controlling the CD45RC(high)/CD45RC(low) Th cell subpopulations may shed light on key regulatory mechanisms of pathogenic immune responses. PMID- 11207244 TI - Induction of polyclonal prostate cancer-specific CTL using dendritic cells transfected with amplified tumor RNA. AB - Polyvalent cancer vaccines targeting the entire antigenic spectrum on tumor cells may represent a superior therapeutic strategy for cancer patients than vaccines solely directed against single Ags. In this study, we show that autologous dendritic cells (DC) transfected with RNA amplified from microdissected tumor cells are capable of stimulating CTL against a broad set of unidentified and critical prostate-specific Ags. Although the polyclonal CTL responses generated with amplified tumor RNA-transfected DC encompassed as a subcomponent a response against prostate-specific Ag (PSA) as well as against telomerase reverse transcriptase, the tumor-specific CTL were consistently more effective than PSA or telomerase reverse transcriptase CTL to lyse tumor targets, suggesting the superiority of the polyclonal response. Although tumor RNA-transfected DC stimulated CTL, which recognized not only tumor but also self-Ags expressed by benign prostate tissue, these cross-reactive CTL were exclusively specific for the PSA, indicating an immunodominant role of PSA in the prostate cancer-specific immune response. Our data suggest that tumor RNA-transfected DC may represent a broadly applicable, potentially clinically effective vaccine strategy for prostate cancer patients, which is not limited by tumor tissue availability for Ag preparation and may minimize the risk of clonal tumor escape. PMID- 11207245 TI - Differential regulation of human blood dendritic cell subsets by IFNs. AB - Based on the relative expression of CD11c and CD1a, we previously identified subsets of dendritic cells (DCs) or DC precursors in human peripheral blood. A CD1a(+)/CD11c(+) population (CD11c(+) DCs), also called myeloid DCs, is an immediate precursor of Langerhans cells, whereas a CD1a(-)/CD11c(-) population (CD11c(-) DCs), sometimes called lymphoid DCs but better known as plasmacytoid DCs, is composed of type I IFN (IFN-alpha beta)-producing cells. Here, we investigate the effects of IFN-alpha beta and IFN-gamma as well as other cytokines on CD11c(+) and CD11c(-) DC subsets, directly isolated from the peripheral blood, instead of in vitro-generated DCs. IFN-gamma and IFN-alpha, rather than GM-CSF, were the most potent cytokines for enhancing the maturation of CD11c(+) DCs. Incubation of CD11c(+) DCs with IFN-gamma also resulted in increased IL-12 production, and this IL-12 allowed DCs to increase Th1 responses by alloreactive T cells. In contrast, IFN-alpha did not induce IL-12 but, rather, augmented IL-10 production. IFN-alpha-primed matured CD11c(+) DCs induced IL-10 producing regulatory T cells; however, this process was independent of the DC derived IL-10. On the other hand, IFN-alpha by itself neither matured CD11c(-) DCs nor altered the polarization of responding T cells, although this cytokine was a potent survival factor for CD11c(-) DCs. Unlike IFN-alpha, IL-3 was a potent survival factor and induced the maturation of CD11c(-) DCs. The IL-3 primed CD11c(-) DCs activated T cells to produce IL-10, IFN-gamma, and IL-4. Thus, CD11c(+) and CD11c(-) DC subsets play distinct roles in the cytokine network, especially their responses to IFNs. PMID- 11207246 TI - CD4 T cell-mediated alloresistance to fully MHC-mismatched allogeneic bone marrow engraftment is dependent on CD40-CD40 ligand interactions, and lasting T cell tolerance is induced by bone marrow transplantation with initial blockade of this pathway. AB - Costimulatory blockade can be used to promote allogeneic marrow engraftment and tolerance induction, but on its own is not 100% reliable. We sought to determine whether one or the other of the CD4 or CD8 T cell subsets of the recipient was primarily responsible for resistance to allogeneic marrow engraftment in mice receiving costimulatory blockade, and to use this information to develop a more reliable, minimal conditioning regimen for induction of mixed chimerism and transplantation tolerance. We demonstrate that a single anti-CD40 ligand mAb treatment is sufficient to completely overcome CD4 cell-mediated resistance to allogeneic marrow engraftment and rapidly induce CD4 cell tolerance, but does not reliably overcome CD8 CTL-mediated alloresistance. The data suggest that costimulation, which activates alloreactive CTL, is insufficient to activate alloreactive CD4 cells when the CD40 pathway is blocked. The addition of host CD8 T cell depletion to anti-CD40 ligand treatment reliably allows the induction of mixed chimerism and donor-specific skin graft tolerance in 3 Gy-irradiated mice receiving fully MHC-mismatched bone marrow grafts. Thus, despite the existence of multiple costimulatory pathways and pathways of APC activation, our studies demonstrate an absolute dependence on CD40-mediated events for CD4 cell-mediated rejection of allogeneic marrow. Exposure to donor bone marrow allows rapid tolerization of alloreactive CD4 cells when the CD40 pathway is blocked, leading to permanent marrow engraftment and intrathymic tolerization of T cells that develop subsequently. PMID- 11207247 TI - Regulatory and effector CD4 T cells in nonobese diabetic mice recognize overlapping determinants on glutamic acid decarboxylase and use distinct V beta genes. AB - The 524--543 region of glutamic acid decarboxylase (GAD65), GAD65(524--543), is one of the first fragments of this islet Ag to induce proliferative T cell responses in the nonobese diabetic (NOD) mouse model of spontaneous autoimmune diabetes. Furthermore, NOD mice given tolerogenic doses of GAD65(524--543) are protected from spontaneous and cyclophosphamide-induced diabetes. In this study, we report that there are at least two I-A(g7)-restricted determinants present in the GAD65(524--543) sequence, each capable of recruiting unique T cell repertoires characterized by distinct TCR V beta gene use. CD4(+) T cells arise spontaneously in young NOD mice to an apparently dominant determinant found within the GAD65 peptide 530--543 (p530); however, T cells to the overlapping determinant 524-538 (p524) dominate the response only after immunization with GAD65(524--543). All p530-responsive T cells used the V beta 4 gene, whereas the V beta 12 gene is preferentially used to encode the TCR of p524-responsive T cell populations. T cell clones and hybridomas from both of these T cell groups were responsive to APC pulsed with GAD65(524--543) or whole rGAD65. p524-reactive cells appeared to be regulatory upon adoptive transfer into young NOD mice and could inhibit insulin-dependent diabetes mellitus development, although they were unable to produce IL-4, IL-10, or TGF beta upon antigenic challenge. Furthermore, we found that i.p. injection with p524/IFA was very effective in providing protection from cyclophosphamide-induced insulin-dependent diabetes mellitus. These data demonstrate that the regulatory T cells elicited by immunizing with GAD65(524--543) are unique and distinct from those that arise from spontaneous endogenous priming, and that T cells to this limited region of GAD65 may be either regulatory or pathogenic. PMID- 11207248 TI - Different NK cell surface phenotypes defined by the DX9 antibody are due to KIR3DL1 gene polymorphism. AB - KIR3DL1 and KIR3DL2 are NK cell receptors for polymorphic HLA-B and -A determinants. The proportion of NK cells that bind anti-KIR3DL1-specific Ab DX9 and their level of binding vary between individuals. To determine whether these differences are due to KIR polymorphism, we assessed KIR3D gene diversity in unrelated individuals and families. Both KIR3DL1 and KIR3DL2 are highly polymorphic genes, with KIR3DS1 segregating like an allele of KIR3DL1. A KIR haplotype lacking KIR3DL1 and KIR3DS1 was defined. The two KIR3DL1 alleles of a heterozygous donor were expressed by different, but overlapping, subsets of NK cell clones. Sequence variation in KIR3DL1 and KIR3DL2 appear distinct; recombination is more evident in KIR3DL1, and point mutation is more evident in KIR3DL2. The KIR3DL1 genotype correlates well with levels of DX9 binding by NK cells, but not with the frequency of DX9-binding cells. Different KIR3DL1 alleles determine high, low, and no binding of DX9 Ab. Consequently, heterozygotes for high and low binding KIR3DL1 alleles have distinct subpopulations of NK cells that bind DX9 at high and low levels, giving characteristic bimodal distributions in flow cytometry. The Z27 Ab gave binding patterns similar to those of DX9. Four KIR3DL1 alleles producing high DX9 binding phenotypes were distinguished from four alleles producing low or no binding phenotypes by substitution at one or more of four positions in the encoded protein: 182 and 283 in the extracellular Ig-like domains, 320 in the transmembrane region, and 373 in the cytoplasmic tail. PMID- 11207249 TI - Cumulative inhibition of NK cells and T cells resulting from engagement of multiple inhibitory Ly49 receptors. AB - Inhibitory receptors specific for MHC class I molecules are expressed on partially overlapping subpopulations of NK cells and memory T cells. A central question pertinent to NK cell development and function is how the combinatorial expression of different receptors with distinct class I specificities affects functional recognition. We therefore studied the quantitative effects resulting from class I engagement of multiple inhibitory Ly49 receptors. We used a transgenic mouse model in which all NK cells and T cells express two different Ly49 receptors with shared class I specificity. Comparisons of cells from these mice with cells from single transgenic mice and wild-type mice revealed that Ly49 receptors cumulatively inhibit lymphocyte effector functions. Multiple Ly49 interactions also had a cumulative impact on NK cell development. The findings suggest that the interactions of inhibitory receptors with class I are interpreted quantitatively rather than as on/off switches. They have intriguing implications concerning NK cell tolerance and reactivity toward cells with extinguished expression of a limited number of class I molecules. PMID- 11207250 TI - CD25+ CD4+ T cells regulate the expansion of peripheral CD4 T cells through the production of IL-10. AB - The mechanisms by which the immune system achieves constant T cell numbers throughout life, thereby controlling autoaggressive cell expansions, are to date not completely understood. Here, we show that the CD25(+) subpopulation of naturally activated (CD45RB(low)) CD4 T cells, but not CD25(-) CD45RB(low) CD4 T cells, inhibits the accumulation of cotransferred CD45RB(high) CD4 T cells in lymphocyte-deficient mice. However, both CD25(+) and CD25(-) CD45RB(low) CD4 T cell subpopulations contain regulatory cells, since they can prevent naive CD4 T cell-induced wasting disease. In the absence of a correlation between disease and the number of recovered CD4(+) cells, we conclude that expansion control and disease prevention are largely independent processes. CD25(+) CD45RB(low) CD4 T cells from IL-10-deficient mice do not protect from disease. They accumulate to a higher cell number and cannot prevent the expansion of CD45RB(high) CD4 T cells upon transfer compared with their wild-type counterparts. Although CD25(+) CD45RB(low) CD4 T cells are capable of expanding when transferred in vivo, they reach a homeostatic equilibrium at lower cell numbers than CD25(-) CD45RB(low) or CD45RB(high) CD4 T cells. We conclude that CD25(+) CD45RB(low) CD4 T cells from nonmanipulated mice control the number of peripheral CD4 T cells through a mechanism involving the production of IL-10 by regulatory T cells. PMID- 11207251 TI - IL-7 administration alters the CD4:CD8 ratio, increases T cell numbers, and increases T cell function in the absence of activation. AB - IL-7 is vital for the development of the immune system and profoundly enhances the function of mature T cells. Chronic administration of IL-7 to mice markedly increases T cell numbers, especially CD8(+) T cells, and enhances T cell functional potential. However, the mechanism by which these effects occur remains unclear. This report demonstrates that only 2 days of IL-7 treatment is needed for maximal enhancement of T cell function, as measured by proliferation, with a 6- to 12-fold increase in the proportion of CD4(+) and CD8(+) T cells in cell cycle by 18 h of ex vivo stimulation. Moreover, a 2-day administration of IL-7 in vivo increases basal proliferation by 4- and 14-fold in CD4(+) and CD8(+) T cells, respectively. These effects occur in the absence of cytokine production, increases in most activation markers, and changes in memory markers. This enhanced basal proliferation is the basis for the increase in T cell numbers in that IL-7 induces an additional 60% and 85% of resting CD4(+) and CD8(+) T cells, respectively, to enter cell cycle in mice given IL-7 for 7 days. These results demonstrate that in vivo administration of IL-7 increases T cell numbers and functional potential via a homeostatic, nonactivating process. These findings may suggest a unique clinical niche for IL-7 in that IL-7 therapy may increase T cell numbers and enhance responses to specific antigenic targets while avoiding a general, nonspecific activation of the T cell population. PMID- 11207252 TI - Potent cytolytic response by a CD8+ CTL clone to multiple peptides from the same protein in association with an allogeneic class I MHC molecule. AB - CTL clone 2C recognizes the allogeneic class I MHC molecule L(d) in association with peptides derived from alpha-ketoglutarate dehydrogenase (oxoglutarate dehydrogenase (OGDH)), a ubiquitous intracellular protein. One of these peptides, QLSPFPFDL (QL9), elicits more vigorous cytolytic responses than two previously identified naturally processed peptides with overlapping sequences, LSPFPFDL (p2Ca) and VAITRIEQLSPFPFDL (p2Cb), from OGDH. In this study, we show that QL9 forms a more stable complex with cell surface L(d) than does p2Ca or p2Cb and is processed from the longer, naturally occurring peptide p2Cb by 20S proteosomes in vitro. The N-terminal cyclized pyroglutaminyl QL9 (pyroQL9), a form of QL9 to which it is converted at the low pH used for peptide isolation from tissue extracts, is even more active than QL9 in cytotoxicity assays with 2C CTL. Overall, the results indicate that along with the abundant natural peptides p2Ca and p2Cb, the QL9 and other OGDH peptides of various lengths, sharing a conserved C-terminal sequence, are also processed and presented with L(d) as allogeneic ligands for T cells expressing 2C TCR. All these peptides, each available in a low amount, could act in concert at the cell surface, resulting in a high density of cognate ligands that accounts for the exceptionally potent cytolytic response by 2C CTL. PMID- 11207253 TI - Fas-mediated apoptosis causes elimination of virus-specific cytotoxic T cells in the virus-infected liver. AB - Immunity to allogeneic MHC Ags is weak in rodent livers, raising questions as to the mechanisms that might control responses in this organ. Infection with an adenovirus vector reveals that T cell-mediated immunity to nonself-Ags in the liver is self-limiting. Virus-induced liver injury decreases and coincides with disappearance of virus-specific CTL, concomitant to an increase of apoptotic T cells early after infection. But whereas death in CD4 cells is independent of Fas, perforin, and TNF-alpha, that of CD8 cells requires Fas and not perforin or TNF-alpha pathways. Fas ligand is expressed on liver-infiltrating cells, pointing to death by fratricide that causes almost complete disappearance of virus specific CTL 4 wk after infection. CTL elimination is virus dose dependent, and high doses induced high alanine aminotransferase values, elevated expression of Fas ligand on CD8 cells, and increased CD8 cell migration into the infected liver. PMID- 11207254 TI - Phenotypic distinction and functional characterization of pro-B cells in adult mouse bone marrow. AB - A lymphoid-committed progenitor population was isolated from mouse bone marrow based on the cell surface phenotype Thy-1.1(neg)Sca-1(pos)c-Kit(low)Lin(neg). These cells were CD43(pos)CD24(pos) on isolation and proliferated in response to the cytokine combination of steel factor, IL-7, and Flt3 ligand. Lymphoid committed progenitors could be segregated into more primitive and more differentiated subsets based on expression of AA4.1. The more differentiated subset generated only B lymphoid cells in 92% of total colonies assayed, lacked T lineage potential, and expressed Pax5. These studies have therefore defined and isolated a B lymphoid-committed progenitor population at a developmental stage corresponding to the initial expression of CD45R. PMID- 11207255 TI - Cell surface-expressed moesin-like receptor regulates T cell interactions with tissue components and binds an adhesion-modulating IL-2 peptide generated by elastase. AB - The adhesion of leukocytes to the extracellular matrix (ECM) depends on their responses to variations in the chemotactic signals in their milieu, as well as on the functioning of cytoskeletal and context-specific receptors. Ezrin, radixin, and moesin constitute a family of proteins that link the plasma membrane to the actin cytoskeleton. The surface expression of moesin on T cells and its role in cell adhesion has not been fully elucidated. Recently, we found that IL-2 peptides generated by elastase modified the adhesion of activated T cells to ECM ligands. Here, we further examined the adhesion regulatory effects of EFLNRWIT, one of the IL-2 peptides, as well as the existence and putative function of its receptor on T cells. We found that when presented to T cells in the absence of another activator, the EFLNRWIT peptide induced cell adhesion to vessel wall and ECM components. Binding of a radiolabeled peptide to T cells, precipitation with the immobilized peptide, and amino acid sequencing of the precipitated protein revealed that EFLNRWIT exerts its function via a cell surface-expressed moesin like moiety, whose constitutive expression on T cells was increased after activation. This notion was further supported by our findings that: 1) anti moesin mAb inhibited the binding of T cells to the immobilized EFLNRWIT peptide, 2) immobilized recombinant moesin bound the IL-2 peptide, and 3) soluble moesin inhibited the EFLNRWIT-induced T cell adhesion to fibronectin. Interestingly, moesin appears to be generally involved in T cell responses to adhesion regulating signals. Thus, the IL-2 peptide EFLNRWIT appears to exert its modulating capacities via an adhesion-regulating moesin-like receptor. PMID- 11207256 TI - The roles of MHC class II, CD40, and B7 costimulation in CTL induction by plasmid DNA. AB - DNA-based vaccines generate potent CTL responses. The mechanism of T cell stimulation has been attributed to plasmid-transfected dendritic cells. These cells have also been shown to express plasmid-encoded proteins and to become activated by surface marker up-regulation. However, the increased surface expression of CD40 and B7 on these dendritic cells is insufficient to overcome the need for MHC class II-restricted CD4(+) T cell help in the priming of a CTL response. In this study, MHC class II(-/-) mice were unable to generate a CTL response following DNA immunization. This deficit in CTL stimulation by MHC class II-deficient mice was only modestly restored with CD40-activating Ab, suggesting that there were other elements provided by MHC class II-restricted T cell help for CTL induction. CTL activity was also augmented by coinjection with a vector encoding the costimulatory ligand B7.1, but not B7.2. These data indicate that dendritic cells in plasmid DNA-injected mice require conditioning signals from MHC class II-restricted T cells that are both CD40 dependent and independent and that there are different roles for costimulatory molecules that may be involved in inducing optimal CTL activity. PMID- 11207257 TI - Stromal cell-derived factor 1 alpha-induced chemotaxis in T cells is mediated by nitric oxide signaling pathways. AB - Stromal cell-derived factor 1 alpha (SDF1 alpha) and its cognate chemokine receptor CXCR4 act as potent chemoattractants and regulate trafficking and homing of hematopoietic progenitor cells and lymphocytes. However, the molecular mechanisms regulating SDF1 alpha-driven cell migration are not well defined. In this study, we have explored the roles of the second messenger NO and the transcription factor NF-kappa B in SDF1 alpha-induced T cell migration. SDF1 alpha treatment of Jurkat T cells increased the activity of NO synthase, which catalyzes the generation of NO. We observed that pretreatment of Jurkat cells or activated PBLs with several NO donors significantly enhanced the SDF1 alpha induced migration, whereas various inhibitors of NO synthase markedly abrogated the chemotactic response in a concentration-dependent manner. Furthermore, we observed that inhibitors of the transcription factor NF-kappa B, which is linked to NO signaling pathways, also significantly blocked the SDF1 alpha-induced chemotactic response. However, these compounds did not have a significant effect on SDF1 alpha-induced mitogen-activated protein kinase activity. In addition, the MAP/Erk kinase kinase inhibitor PD98059 did not abrogate SDF1 alpha-induced chemotaxis. AKT, which has been shown to mediate NO production, was also phosphorylated upon SDF1 alpha stimulation. These studies suggest that NO-related signaling pathways may mediate SDF1 alpha-induced chemotaxis, but not mitogen activated protein kinase activation. PMID- 11207258 TI - The production of IFN-gamma by IL-12/IL-18-activated macrophages requires STAT4 signaling and is inhibited by IL-4. AB - Macrophages release IFN-gamma on combined stimulation with IL-12 and IL-18, but the signaling requirements of this process and its regulation by other cytokines are unknown. Here, we demonstrate that STAT4 is indispensable for IL-12/IL-18 induced production of IFN-gamma by mouse peritoneal macrophages. Type 2 NO synthase (NOS2), which we previously found to be a prerequisite for IL-12-induced IFN-gamma production in NK cells, was not required for IFN-gamma production by these macrophages. IL-12 alone already induced the expression of IFN-gamma mRNA, but nuclear translocation of STAT4, the release of IFN-gamma protein, and the subsequent production of NO was strictly dependent on the simultaneous presence of IL-18. NF-kappa B, which mediates IL-18 effects in T cells, was only weakly activated by IL-12 and/or IL-18 in macrophages. Known inhibitors of macrophage functions (e.g., IL-4 and TGF-beta) also suppressed macrophage IFN-gamma production and the subsequent production of NOS2-derived NO. The inhibitory effect of IL-4 was paralleled by nuclear translocation of STAT6, which in EMSAs was able to bind to the same DNA oligonucleotide as STAT4. These results further define the production of IFN-gamma by macrophages and point to a diversity in the signals required for IFN-gamma production by various cell types. PMID- 11207259 TI - Expression of a V region-less B cell receptor confers a tolerance-like phenotype on transgenic B cells. AB - Neoplastic B cells from H chain disease patients express a truncated B cell receptor (BCR), comprising a membrane Ig that lacks part of its extracellular domain. It has been speculated that deletion of the Ag binding domain would confer a constitutive activity on the BCR, as it has been shown for oncogenic growth factor receptors. A V region-less BCR has constitutive activity, because in transgenic mice it causes inhibition of endogenous H chain gene rearrangements and relieves the requirement for surrogate L chain in pre-B cell development. However, it has been speculated that normal Ag receptors also display constitutive activity. Here we show that transgenic B cells expressing a membrane H chain disease protein on their surface are phenotypically and functionally similar to B cells developing in the presence of their cognate Ag and that cells with normal levels of mutant BCR are eliminated in spleen via a bcl-2 sensitive pathway while progressing toward the mature stage. In contrast, cells with lower levels of mutant receptors develop as mature B cells. These findings support the view that the truncated BCR has a constitutive activity that mimics ligand binding, in analogy to what has been shown for oncogenic growth factor receptors. PMID- 11207260 TI - Involvement of CD1 in peripheral deletion of T lymphocytes is independent of NK T cells. AB - During peripheral T cell deletion, lymphocytes accumulate in nonlymphoid organs including the liver, a tissue that expresses the nonclassical, MHC-like molecule, CD1. Injection of anti-CD3 Ab results in T cell activation, which in normal mice is followed by peripheral T cell deletion. However, in CD1-deficient mice, the deletion of the activated T cells from the lymph nodes was impaired. This defect in peripheral T cell deletion was accompanied by attenuated accumulation of CD8(+) T cells in the liver. In tetra-parental bone marrow chimeras, expression of CD1 on the T cells themselves was not required for T cell deletion, suggesting a role for CD1 on other cells with which the T cells interact. We tested whether this role was dependent on the Ag receptor-invariant, CD1-reactive subset of NK T cells using two other mutant mouse lines that lack most NK T cells, due to deletion of the genes encoding either beta(2)-microglobulin or the TCR element J alpha 281. However, these mice had no abnormality of peripheral T cell deletion. These findings indicate a novel role for CD1 in T cell deletion, and show that CD1 functions in this process through mechanisms that does not involve the major, TCR-invariant set of NK T cells. PMID- 11207261 TI - Src homology 2 domain-containing protein-tyrosine phosphatases, SHP-1 and SHP-2, are required for platelet endothelial cell adhesion molecule-1/CD31-mediated inhibitory signaling. AB - Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) is a newly assigned member of the Ig immunoreceptor tyrosine-based inhibitory motif superfamily, and its functional role is suggested to be an inhibitory receptor that modulates immunoreceptor tyrosine-based activation motif-dependent signaling cascades. To test whether PECAM-1 is capable of delivering inhibitory signals in B cells and the functional requirement of protein-tyrosine phosphatases (PTPs) for this inhibitory signaling, we generated chimeric Fc gamma RIIB1-PECAM-1 receptors containing the extracellular and transmembrane portions of murine Fc gamma RIIB1 and the cytoplasmic domain of human PECAM-1. These chimeric receptors were stably expressed in chicken DT40 B cells either as wild-type or mutant cells deficient in SHP-1(-/-), SHP-2(-/-), SHIP(-/-), or SHP-1/2(-/-) and then assessed for their ability to inhibit B cell Ag receptor (BCR) signaling. Coligation of wild-type Fc gamma RIIB1-PECAM-1 with BCR resulted in inhibition of intracellular calcium release, suggesting that the cytoplasmic domain of PECAM-1 is capable of delivering an inhibitory signal that blocks BCR-mediated activation. This PECAM-1 mediated inhibitory signaling correlated with tyrosine phosphorylation of the Fc gamma RIIB1-PECAM-1 chimera, recruitment of SHP-1 and SHP-2 PTPs by the phosphorylated chimera, and attenuation of calcium mobilization responses. Mutational analysis of the two tyrosine residues, 663 and 686, constituting the immunoreceptor tyrosine-based inhibitory motifs in PECAM-1 revealed that both tyrosine residues play a crucial role in the inhibitory signal. Functional analysis of various PTP-deficient DT40 B cell lines stably expressing wild-type chimeric Fc gamma RIIB1-PECAM-1 receptor indicated that cytoplasmic Src homology 2-domain-containing phosphatases, SHP-1 and SHP-2, were both necessary and sufficient to deliver inhibitory negative regulation upon coligation of BCR complex with inhibitory receptor. PMID- 11207262 TI - Functional expression of a costimulatory B7.2 (CD86) protein on human salivary gland epithelial cells that interacts with the CD28 receptor, but has reduced binding to CTLA4. AB - B7 molecules expressed on classic APC play a critical role in the regulation of immune responses by providing activation or inhibitory signals to T cells, through the ligation with CD28 or CTLA4 receptors, respectively. We have recently described the expression of B7 molecules by the salivary gland epithelial cells (SGEC) of patients with Sjogren's syndrome (also termed autoimmune epithelitis). The role of such expression needs to be clarified. Thus, in the present study, we sought to address the existence and function of B7.2 proteins on cultured nonneoplastic SGEC lines derived from Sjogren's syndrome patients. The occurrence of B7.2 proteins on SGEC was verified by flow cytometry, immunocytochemistry, immunoprecipitation, and immunoblotting. The assessment of several cell lines in costimulation assays had revealed that the constitutive expression of B7.2 molecules is sufficient to provide costimulatory signals to anti-CD3-stimulated T cells. SGEC-derived costimulation induced IL-2-dependent proliferation of CD4(+) T cells, which was associated with low production of IL-2, but probably also with the secretion of yet undefined autocrine T cell growth factor(s). B7.2 proteins expressed by SGEC were found to display distinctive binding properties denoted by the functional interaction with CD28 receptor and reduced binding to CTLA4. Finally, the detection of a functional soluble form of B7.2 protein in cell-free culture supernatants of both SGEC and EBV-transformed B cell lines is demonstrated. These findings imply a critical role for epithelial cells in the regulation of local immune responses in the salivary glands. PMID- 11207263 TI - Oral tolerance revisited: prior oral tolerization abrogates cholera toxin-induced mucosal IgA responses. AB - Oral delivery of a large dose or prolonged feeding of protein Ags induce systemic unresponsiveness most often characterized as reduced IgG and IgE Ab- and Ag specific CD4(+) T cell responses. It remains controversial whether oral tolerance extends to diminished mucosal IgA responses in the gastrointestinal tract. To address this issue, mice were given a high oral dose of OVA or PBS and then orally immunized with OVA and cholera toxin as mucosal adjuvant, and both systemic and mucosal immune responses were assessed. OVA-specific serum IgG and IgA and mucosal IgA Ab levels were markedly reduced in mice given OVA orally compared with mice fed PBS. Furthermore, when OVA-specific Ab-forming cells (AFCs) in both systemic and mucosa-associated tissues were examined, IgG AFCs in the spleen and IgA AFCs in the gastrointestinal tract lamina propria of mice given OVA orally were dramatically decreased. Furthermore, marked reductions in OVA-specific CD4(+) T cell proliferative and cytokine responses in spleen and Peyer's patches were seen in mice given oral OVA but were unaffected in PBS-fed mice. We conclude that high oral doses of protein induce both mucosal and systemic unresponsiveness and that use of mucosal adjuvants that induce both parenteral and mucosal immunity may be a better way to assess oral tolerance. PMID- 11207264 TI - Antigen receptor proximal signaling in splenic B-2 cell subsets. AB - Splenic marginal zone (MZ) and follicular mantle (FO) B cells differ in their responses to stimuli in vitro and in vivo. We have previously shown that MZ cells exhibit greater calcium responses after ligation of membrane IgM (mIgM). We have now investigated the molecular mechanism underlying the difference in calcium responses following ligation of mIgM and studied the response to total B cell receptor ligation in these two subsets. We compared key cellular proteins involved in calcium signaling in MZ and FO cells. Tyrosine phosphorylation and activity of phospholipase C-gamma 2 and Syk protein tyrosine kinase were significantly higher in MZ cells than in FO cells after mIgM engagement, providing a likely explanation for our previous findings. Tyrosine phosphorylation of CD22 and expression of Src homology 2-containing inositol phosphatase and Src homology 2-containing protein tyrosine phosphatase-1 were also higher in the MZ cells. Expression and tyrosine phosphorylation of Btk, BLNK, Vav, or phosphatidylinositol 3-kinase were equivalent. In contrast, stimulation with anti-kappa induced equivalent increases in calcium and activation of Syk in the two subsets. These signals were also equivalent in cells from IgM transgenic, J(H) knockout mice, which have equivalent levels of IgM in both subsets. With total spleen B cells, Btk was maximally phosphorylated at a lower concentration of anti-kappa than Syk. Thus, calcium signaling in the subsets of mature B cells reflects the amount of Ig ligated more than the isotype or the subset and this correlates with the relative tyrosine phosphorylation of Syk. PMID- 11207265 TI - Proteasomes modulate balance among proapoptotic and antiapoptotic Bcl-2 family members and compromise functioning of the electron transport chain in leukemic cells. AB - The mechanism underlying apoptosis induced by proteasome inhibition in leukemic Jurkat and Namalwa cells was investigated in this study. The proteasome inhibitor lactacystin differentially regulated the protein levels of proapoptotic Bcl-2 family members and Bik was accumulated at the mitochondria. Bik overexpression sufficed to induce apoptosis in these cells. Detailed examination along the respiration chain showed that lactacystin compromised a step after complex III, and exogenous cytochrome c could overcome this compromise. Probably as a result, the succinate-stimulated generation of mitochondrial membrane potential was significantly diminished. Bcl-x(L) interacted with Bik in the cells, and Bcl-x(L) overexpression prevented cytochrome c leakage out of the mitochondria, corrected the mitochondrial membrane potential defect, and protected the cells from apoptosis. These results show that proteasomes can modulate apoptosis of lymphocytes by affecting the half-life of Bcl-2 family members, Bik being one of them. PMID- 11207266 TI - Regulation and function of T1/ST2 expression on CD4+ T cells: induction of type 2 cytokine production by T1/ST2 cross-linking. AB - The orphan receptor T1/ST2, a member of the IL-1R family, is preferentially expressed on the surface of murine Th2 cells. In this study, we analyzed the kinetics and function of T1/ST2 expression on Th2 cells in vitro. Whereas naive CD4(+) cells did not express T1/ST2, most CD4(+) cells became T1/ST2(+) upon repeated antigenic stimulation under Th2-polarizing conditions. Flow cytometric analyses revealed that the kinetics of T1/ST2 expression on Th2 cells was delayed compared with the kinetics of type 2 cytokine production. Exogenous IL-6, IL-5, IL-1, and TNF-alpha enhanced the expression of T1/ST2 on Th2 cells, and IL-6 was by far most effective in this regard. However, the expression of T1/ST2 did not depend on the presence of IL-6 and was also detected in IL-6-deficient mice. Most important, cross-linking of T1/ST2 provided a costimulatory signal for Th2 but not Th1 cells and directly induced proliferation and type 2 cytokine production. Thus, T1/ST2 is not only a Th2 cell marker but also plays an important role in the activation of Th2 cells. PMID- 11207267 TI - Single-cell analyses reveal two defects in peptide-specific activation of naive T cells from aged mice. AB - Confocal fluorescent microscopy was used to study redistribution of membrane associated proteins in naive T cells from young and old mice from a transgenic stock whose T cells express a TCR specific for a peptide derived from pigeon cytochrome C. About 50% of the T cells from young mice that formed conjugates with peptide-pulsed APC were found to form complexes, at the site of binding to the APC, containing CD3epsilon, linker for activation of T cells (LAT), and Zap 70 in a central area and c-Cbl, p95(vav), Grb-2, PLC gamma, Fyn, and Lck distributed more uniformly across the interface area. Two-color staining showed that those cells that were able to relocalize c-Cbl, LAT, CD3epsilon, or PLC gamma typically relocalized all four of these components of the activation complex. About 75% of conjugates that rearranged LAT, c-Cbl, or PLC gamma also exhibited cytoplasmic NF-AT migration to the T cell nucleus. Aging had two effects. First, it led to a diminution of approximately 2-fold in the proportion of T cell/APC conjugates that could relocalize any of the nine tested proteins to the immune synapse. Second, aging diminished by approximately 2-fold the frequency of cytoplasmic NF-AT migration among cells that could generate immune synapses containing LAT, c-Cbl, or PLC gamma. Thus naive CD4 T cells from old mice exhibit at least two separable defects in the earliest stages of activation induced by peptide/MHC complexes. PMID- 11207268 TI - The identification and characterization of a ligand for bovine CD5. AB - CD5, a type I glycoprotein expressed by T cells and a subset of B cells, is thought to play a significant role in modulating Ag receptor signaling. Previously, our laboratory has shown that bovine B cells are induced to express this key regulatory molecule upon Ag receptor cross-linking. To date, a ligand has not been described for bovine CD5. Given the importance ligand binding presumably plays in the functioning of CD5 on this B cell subset and on T cells, we sought to characterize the ligand for this protein using a bovine CD5-human IgG1 (CD5Ig) fusion protein produced by both mammalian and yeast cells. As determined by CD5Ig binding, expression of this ligand is negative to low on freshly isolated lymphocytes, with low-density expression being limited to activated B cells. Activation with LPS, PMA, and calcium ionophore, or ligation of CD40 alone or in combination with anti-IgM, resulted in B cell-specific expression of this ligand. Interestingly, activation through B cell Ag receptor cross-linking alone, although able to induce CD5 expression, did not result in expression of CD5 ligand (CD5L). In addition, we demonstrate a functional role for CD5L as a costimulatory molecule that augments CD40L-stimulated B cell proliferation. Finally, immunoprecipitation with CD5Ig suggests that the ligand characterized in this study has a molecular mass of approximately 200 kDa. The data reported herein, as well as future studies aimed at further characterizing this newly identified bovine CD5L, will undoubtedly aid in understanding the role that the CD5-CD5L interaction plays in immune responses. PMID- 11207269 TI - Activation of the EBV/C3d receptor (CR2, CD21) on human B lymphocyte surface triggers tyrosine phosphorylation of the 95-kDa nucleolin and its interaction with phosphatidylinositol 3 kinase. AB - We previously demonstrated that CR2 activation on human B lymphocyte surface triggered tyrosine phosphorylation of a p95 component and its interaction with p85 subunit of phosphatidylinositol 3' (PI 3) kinase. Despite identical molecular mass of 95 kDa, this tyrosine phosphorylated p95 molecule was not CD19, the proto oncogene Vav, or the adaptator Gab1. To identify this tyrosine phosphorylated p95 component, we first purified it by affinity chromatography on anti phosphotyrosine mAb covalently linked to Sepharose 4B, followed by polyacrylamide gel electrophoresis. Then, the isolated 95-kDa tyrosine phosphorylated band was submitted to amino acid analysis by mass spectrometry; the two different isolated peptides were characterized by amino acid sequences 100% identical with two different domains of nucleolin, localized between aa 411--420 and 611--624. Anti nucleolin mAb was used to confirm the antigenic properties of this p95 component. Functional studies demonstrated that CR2 activation induced, within a brief span of 2 min, tyrosine phosphorylation of nucleolin and its interaction with Src homology 2 domains of the p85 subunit of PI 3 kinase and of 3BP2 and Grb2, but not with Src homology 2 domains of Fyn and Gap. These properties of nucleolin were identical with those of the p95 previously described and induced by CR2 activation. Furthermore, tyrosine phosphorylation of nucleolin was also induced in normal B lymphocytes by CR2 activation but neither by CD19 nor BCR activation. These data support that tyrosine phosphorylation of nucleolin and its interaction with PI 3 kinase p85 subunit constitute one of the earlier steps in the specific intracellular signaling pathway of CR2. PMID- 11207270 TI - Ligation of 4-1BB (CDw137) regulates graft-versus-host disease, graft-versus leukemia, and graft rejection in allogeneic bone marrow transplant recipients. AB - 4-1BB is expressed on activated CD4(+) and CD8(+) T cells; its ligand, 4-1BB ligand is expressed on APCs. Despite expression on both T cell subpopulations, 4 1BB has been reported to predominantly affect CD8(+) T cell responses. By quantifying graft-vs-host disease alloresponses in vivo, we demonstrate that both CD4(+) and CD8(+) T cell-mediated alloresponses are regulated by 4-1BB/4-1BB ligand interactions to approximately the same extent. 4-1BB receptor-facilitated CD4(+) T cell-mediated alloresponses were partly CD28 independent. In two distinct marrow graft rejection systems, host CD8(+) and CD4(+) T cells each separately contributed to host anti-donor T cell-mediated allograft rejection. alpha 4-1BB mAb increased the graft-vs-leukemia effect of a suboptimal number of donor splenocytes given later post bone marrow transplantation by bolstering allogeneic responses resulting in leukemia elimination. In summary, 4-1BB ligation is a potent regulator of CD4(+) and CD8(+) T cell-mediated allogeneic responses in vivo. Modifying the ligation of 4-1BB represents a new approach to altering the graft-vs-host disease and graft-vs-leukemia effects of allogeneic T cells post bone marrow transplantation. PMID- 11207272 TI - Anergy and not clonal ignorance determines the fate of B cells that recognize a physiological autoantigen. AB - Autoantibodies to insulin arise spontaneously in the insulin autoimmune syndrome and in type I diabetes. In addition, administration of insulin to individuals without autoimmune disease routinely results in Abs that bind autologous hormone. These observations and findings in transgenic models of tolerance led to an inference that physiological levels of hormones and growth factors, such as insulin, are not sufficient to induce tolerance in B cells, a state termed clonal ignorance. In contrast, we have discovered that virtually all conventional B cells expressing a low affinity anti-insulin transgene interact with endogenous insulin and are effectively silenced for Ig production and for T cell-dependent immune responses. A fraction of transgenic B cells escapes silencing and functions autonomously to produce insulin Abs that may lower fasting blood sugars similar to an insulin autoimmune syndrome. These B cells have characteristics of a B1-like subset and are depleted by hypotonic peritoneal lysis. These findings question the concept of clonal ignorance and show that physiological concentrations of Ag may effectively silence conventional B cells even when the affinity for autoantigen is low. Self-reactivity may arise in the repertoire because of compartmental differences that govern the fate of B cells and not as a result of true clonal ignorance. PMID- 11207271 TI - Premature TCR alpha beta expression and signaling in early thymocytes impair thymocyte expansion and partially block their development. AB - In thymocyte ontogeny, Tcr-a genes rearrange after Tcr-b genes. TCR alpha beta transgenic (Tg) mice have no such delay, consequently expressing rearranged TCR alpha beta proteins early in the ontogeny. Such mice exhibit reduced thymic cellularity and accumulate mature, nonprecursor TCR(+)CD8(-)4(-) thymocytes, believed to be caused by premature Tg TCR alpha beta expression via unknown mechanism(s). Here, we show that premature expression of TCR alpha beta on early thymocytes curtails thymocyte expansion and impairs the CD8(-)4(-) --> CD8(+)4(+) transition. This effect is accomplished by two distinct mechanisms. First, the early formation of TCR alpha beta appears to impair the formation and function of pre-TCR, consistent with recently published results. Second, the premature TCR alpha beta contact with intrathymic MHC molecules further pronounces the block in proliferation and differentiation. These results suggest that the benefit of asynchronous Tcr-a and Tcr-b rearrangement is not only to minimize waste during thymopoiesis, but also to simultaneously allow proper expression/function of the pre-TCR and to shield CD8(-)4(-) thymocytes from TCR alpha beta signals that impair thymocyte proliferation and CD8(-)4(-) --> CD8(+)4(+) transition. PMID- 11207273 TI - Uncoupling p70(s6) kinase activation and proliferation: rapamycin-resistant proliferation of human CD8(+) T lymphocytes. AB - Rapamycin is a fungal macrolide that inhibits the proliferation of T cells. Studies in both animals and humans have found that rapamycin significantly reduces graft rejection. However, though CD8(+) T cells are involved in graft infiltration and rejection, little is known regarding the effects of rapamycin on CD8(+) human T cell responses. In this study, we examined the mechanism of rapamycin-induced inhibition of Ag-driven activation of CD8(+) T cells. Surprisingly, a heterogeneous proliferative response in the presence of rapamycin was observed among different Ag-specific CD8(+) T cell clones; this was also observed in CD8(+) peripheral blood T cells activated with TCR cross-linking ex vivo. Inhibition of T cell proliferation by rapamycin was controlled by both the strength of signal delivered through the Ag receptor as well as the specific costimulatory signals received by the T cell. Rapamycin-resistant proliferation occurred despite inhibition of p70(s6) kinase activity. Moreover, rapamycin resistant proliferation of the CD8(+) T cell clones was blocked by anti-IL-2 Abs, suggesting that while some of the parallel pathways triggered by IL-2R signaling are sensitive to the effects of rapamycin, others account for the Ag-driven rapamycin resistance. These data provide a new framework for examining the specific mechanism of action of rapamycin in human disease. PMID- 11207274 TI - In vivo CD40-CD154 (CD40 ligand) interaction induces integrated HIV expression by APC in an HIV-1-transgenic mouse model. AB - Because of their relative resistance to viral cytopathic effects, APC can provide an alternative reservoir for latently integrated HIV. We used an HIV-transgenic mouse model in which APC serve as the major source of inducible HIV expression to study mechanisms by which integrated virus can be activated in these cells. When admixed with transgenic APC, activated T lymphocytes provided a major contact dependent stimulus for viral protein expression in vitro. Using blocking anti CD154 mAb as well as CD154-deficient T cells, the HIV response induced by activated T lymphocytes was demonstrated to require CD40-CD154 interaction. The role of this pathway in the induction of HIV expression from APC in vivo was further studied in an experimental model involving infection of the HIV transgenic mice with PLASMODIUM: chabaudi parasites. Enhanced viral production by dendritic cells and macrophages in infected mice was associated with up-regulated CD40 expression. More importantly, in vivo treatment with blocking anti-CD154 mAb markedly reduced viral expression in P. chabaudi-infected animals. Together, these findings indicate that immune activation of integrated HIV can be driven by the costimulatory interaction of activated T cells with APC. Because chronic T cell activation driven by coinfections as well as HIV-1 itself is a characteristic of HIV disease, this pathway may be important in sustaining viral expression from APC reservoirs. PMID- 11207275 TI - The granzyme B inhibitor, protease inhibitor 9, is mainly expressed by dendritic cells and at immune-privileged sites. AB - Granzyme B is released from CTLs and NK cells and an important mediator of CTL/NK induced apoptosis in target cells. The human intracellular serpin proteinase inhibitor (PI)9 is the only human protein able to inhibit the activity of granzyme B. As a first step to elucidate the physiological role of PI9, PI9 protein expression in various human tissues was studied. A mAb directed against human PI9 was developed, which specifically stained PI9-transfected COS-7 cells, and was used for immunohistochemistry. Both in primary lymphoid organs and in inflammatory infiltrates, PI9 was present in different subsets of dendritic cells. Also T-lymphocytes in primary and organ-associated lymphoid tissues were PI9 positive. Endothelial cells of small vessels in most organs tested as well as the endothelial layer of large veins and arteries showed strong PI9 staining. Surprisingly, high PI9 protein expression was also found at immune-privileged sites like the placenta, the testis, the ovary, and the eye. These data fit with the hypothesis that PI9 is expressed at sites where degranulation of CTL or NK cells is potentially deleterious. PMID- 11207276 TI - The T cell-dependent B cell immune response and germinal center reaction are intact in A-myb-deficient mice. AB - Expression of the protooncogene A-myb is restricted to the developing CNS, adult testes, breasts in late pregnancy, and germinal centers of secondary B cell follicles. The functional relevance of A-myb expression at three of these sites has been demonstrated previously via the generation and analysis of A-myb deficient mice, which display behavioral abnormalities, male sterility, and perturbed breast development during pregnancy. In contrast, here we show that the germinal center response driven by T cell-dependent Ag immunization and the associated processes of Ab V gene somatic hypermutation, affinity maturation, and heavy chain class switching are overtly normal in A-myb-deficient mice. Nonetheless, these mice display mild splenic white pulp hypoplasia and blunted primary serum Ab responses, suggesting that although A-myb is not directly involved in the regulation of the memory B cell response, it may play a role in enhancing peripheral B cell survival or proliferative capacity. PMID- 11207277 TI - The globular heads of C1q specifically recognize surface blebs of apoptotic vascular endothelial cells. AB - Complement protein C1q is required to maintain immune tolerance. The molecular mechanism responsible for this link has not been determined. We have previously demonstrated that C1q binds directly and specifically to surface blebs of apoptotic human keratinocytes, suggesting that it may participate in clearance of self Ags generated during programmed cell death. Here, we demonstrate that C1q also binds directly to apoptotic blebs of vascular endothelial cells and PBMC. These apoptotic cells are recognized by the globular heads of C1q, which bind specifically to the surface blebs, and deposition increases as the blebs mature on the cell surface. These observations suggest that C1q may participate in the clearance of apoptotic cells from the circulation and from the walls of the vascular lumen. The interaction of surface blebs with the globular heads of C1q suggests that surface blebs may be capable of directly activating the classical pathway of complement under certain circumstances, generating C4- and C3-derived ligands for receptors such as CR1, CR2, CR3, and CR4. Appropriate recognition of apoptotic cells by C1q and targeted clearance of the molecular contents of surface blebs to complement receptors may be critical for the maintenance of immune tolerance. PMID- 11207278 TI - CD95 ligand-expressing tumors are rejected in anti-tumor TCR transgenic perforin knockout mice. AB - CD95 (APO-/Fas) ligand (CD95L) is a member of the TNF family predominantly expressed by activated T and NK cells but also by tumors of diverse cellular origin. CD95L trimerizes surface CD95 expressed by target cells that subsequently undergo apoptosis. The role of the CD95/CD95L system in the down-regulation of an immune response (activation-induced cell death) is established. However, it is so far unclear why tumors express CD95L. To investigate whether tumors use the CD95L to down-regulate an anti-tumor immune response, we established a transgenic (tg) mouse model consisting of 1) apoptosis-resistant tumor cells, designated LKC CD95L, which express functional CD95L and the model tumor Ag K(b); and 2) perforin knockout (PKO) anti-K(b) TCR tg mice. L1210-Fas antisense expressing K(b), crmA, and CD95L (LKC-CD95L) killed CD95(+) unrelated tumor targets and Con A-activated splenocytes from anti-K(b) TCR tg PKO mice by a CD95L-dependent mechanism in vitro. However, we could not detect any cytotoxic activity against anti-tumor (anti-K(b)) T cells in vivo. We also observed reduced growth of LKC CD95L in nude mice and rapid rejection in anti-K(b) TCR tg PKO mice. Because the tumor cells are resistant to CD95L-, TNF-alpha-, and TNF-related apoptosis inducing ligand-induced apoptosis and the mice used are perforin-deficient, the involvement of these four cytotoxicity mechanisms in tumor rejection can be excluded. The histological examination of tumors grown in nude mice showed infiltration of LKC-CD95L tumors by neutrophils, whereas L1210-Fas antisense expressing K(b) and crmA (LKC) tumor tissue was neutrophil-free. Chemotaxis experiments revealed that CD95L has no direct neutrophil-attractive activity. Therefore, we conclude that LKC-CD95L cells used an indirect mechanism to attract neutrophils that may cause tumor rejection. PMID- 11207279 TI - Immunobiology of allograft rejection in the absence of IFN-gamma: CD8+ effector cells develop independently of CD4+ cells and CD40-CD40 ligand interactions. AB - Both wild-type (WT) and IFN-gamma-deficient (IFN-gamma(-/-)) C57BL/6 mice can rapidly reject BALB/c cardiac allografts. When depleted of CD8(+) cells, both WT and IFN-gamma(-/-) mice rejected their allografts, indicating that these mice share a common CD4-mediated, CD8-independent mechanism of rejection. However, when depleted of CD4(+) cells, WT mice accepted their allografts, while IFN gamma(-/-) recipients rapidly rejected them. Hence, IFN-gamma(-/-), but not WT mice developed an unusual CD8-mediated, CD4-independent, mechanism of allograft rejection. Allograft rejection in IFN-gamma(-/-) mice was associated with intragraft accumulation of IL-4-producing cells, polymorphonuclear leukocytes, and eosinophils. Furthermore, this form of rejection was resistant to treatment with anti-CD40 ligand (CD40L) mAb, which markedly prolonged graft survival in WT mice. T cell depletion studies verified that anti-CD40L treatment failed to prevent CD8-mediated allograft rejection in IFN-gamma(-/-) mice. However, anti CD40L treatment did prevent CD4-mediated rejection in IFN-gamma(-/-) mice, although grafts were eventually rejected when CD8(+) T cells repopulated the periphery. The IL-4 production and eosinophil influx into the graft that occurred during CD8-mediated rejection were apparently epiphenomenal, since treatment with anti-IL-4 mAb blocked intragraft accumulation of eosinophils, but did not interfere with allograft rejection. These studies demonstrate that a novel, CD8 mediated mechanism of allograft rejection, which is resistant to experimental immunosuppression, can develop when IFN-gamma is limiting. An understanding of this mechanism is confounded by its association with Th2-like immune events, which contribute unique histopathologic features to the graft but are apparently unnecessary for the process of allograft rejection. PMID- 11207280 TI - Functional association of CD9 with the Fc gamma receptors in macrophages. AB - CD9, a member of the tetraspan family of proteins, is highly expressed on macrophages. Although a clear function for the molecule has yet to be described, we have found that the anti-CD9 mAb activates mouse macrophages. The rat anti-CD9 mAb, KMC8.8, but not the F(ab')(2), induced tyrosine phosphorylation of proteins including syk and cbl and induced cell aggregation in the mouse macrophage cell line, J774, suggesting that co-cross-linking of CD9 and Fc gamma R was required for the signal. Co-cross-linking of CD9-Fc gamma R with KMC8.8 on macrophages from three different FcR-deficient mice, FcR gamma-chain(-/-), Fc gamma RIIB(-/ ), and Fc gamma RIII(-/-), revealed that Fc gamma RIII is specific and crucial for syk phosphorylation. Although both KMC8.8 and the anti-Fc gamma RIIB/III mAb, 2.4G2, evoked similar phosphorylation patterns, only KMC8.8 induced cell aggregation. Additionally, KMC8.8 treatment led to reduce levels of TNF-alpha production and p42/44 extracellular signal-related kinase phosphorylation relative to 2.4G2 stimulation. Immunofluorescence staining showed that co-cross linking of CD9-Fc gamma R with KMC8.8 induced filopodium extension before cell aggregation, which was followed by simultaneous colocalization of CD9, Fc gamma RIIB/III, Mac-1, ICAM-1, and F-actin at the cell-cell adhesion site. Moreover, KMC8.8 treatment of Fc gamma R-deficient macrophages revealed that the colocalization of CD9, Fc gamma RIII, Mac-1, and F-actin requires co-cross linking of CD9-Fc gamma RIII, whereas co-cross-linking of CD9-Fc gamma RIIB induced the colocalization of only CD9 and Fc gamma RIIB. Our results demonstrate that co-cross-linking of CD9 and Fc gamma Rs activates macrophages; therefore, CD9 may collaborate with FcRs functioning in infection and inflammation on macrophages. PMID- 11207282 TI - Notch signaling suppresses IgH gene expression in chicken B cells: implication in spatially restricted expression of Serrate2/Notch1 in the bursa of Fabricius. AB - The bursa of Fabricius is a central organ for chicken B cell development and provides an essential microenvironment for expansion of the B cell pool and for generation of a diversified B cell repertoire. We report here that genes encoding the Notch family of transmembrane proteins, key regulators of cell fate determination in development, are differentially expressed in the bursa of Fabricius: Notch1 is expressed in medullary B cells located close to the basement membrane-associated epithelium (BMAE). In contrast, a Notch ligand, Serrate2, is expressed exclusively in the BMAE, which surrounds bursal medulla. A basic helix loop-helix-type transcription factor, Hairy1, a downstream target of Notch signaling, is expressed in the bursa coordinately with Notch1 and Serrate2 and an immature B cell line, TLT1, which expresses both Notch1 and Serrate2. Furthermore, stable expression of a constitutively active form of chicken Notch1 or Notch2 in a B cell line results in a down-regulation of surface IgM expression, which is accompanied by the reduction of IgH gene transcripts. Transient reporter assay with the human IgH gene intronic enhancer reveals that an active form of Notch1 inhibits the IgH enhancer activity in chicken B cells, suggesting that Notch-mediated signals suppress the IgH gene expression via influencing the IgH intronic enhancer. These findings raise the possibility that the local activation of Notch1 in a subset of B cells by Serrate2 expressed in BMAE may influence the cell fate decision that is involved in B cell differentiation and selection inside the bursa. PMID- 11207283 TI - The dendritic cell-specific CC-chemokine DC-CK1 is expressed by germinal center dendritic cells and attracts CD38-negative mantle zone B lymphocytes. AB - DC-CK1 (CCL18) is a dendritic cell (DC)-specific chemokine expressed in both T and B cell areas of secondary lymphoid organs that preferentially attracts CD45RA(+) T cells. In this study, we further explored the nature of DC-CK1 expressing cells in germinal centers (GCs) of secondary lymphoid organs using a newly developed anti-DC-CK1 mAb. Immunohistochemical analysis demonstrated a remarkable difference in the number of DC-CK1 expressing cells in adjacent GCs within one tonsil, implicating that the expression of DC-CK1 in GCs depends on the activation and/or progression stage of the GC reaction. Using immunohistology and RNA analysis, we demonstrated that GCDC are the source of DC-CK1 production in the GCs. Considering the recently described function of GCDC in (naive) B cell proliferation, isotype switching and Ab production, we investigated the ability of DC-CK1 to attract B lymphocytes. Here we demonstrate that DC-CK1 is a pertussis toxin-dependent chemoattractant for B lymphocytes with a preference in attracting mantle zone (CD38(-)) B cells. The findings that GCDC produce DC-CK1 and attract mantle zone B cells support a key role for GCDC in the development of GCs and memory B cell formation. PMID- 11207281 TI - MHC class I-related neonatal Fc receptor for IgG is functionally expressed in monocytes, intestinal macrophages, and dendritic cells. AB - The neonatal Fc receptor (FcRn) for IgG, an MHC class I-related molecule, functions to transport IgG across polarized epithelial cells and protect IgG from degradation. However, little is known about whether FcRn is functionally expressed in immune cells. We show here that FcRn mRNA was identifiable in human monocytes, macrophages, and dendritic cells. FcRn heavy chain was detectable as a 45-kDa protein in monocytic U937 and THP-1 cells and in purified human intestinal macrophages, peripheral blood monocytes, and dendritic cells by Western blot analysis. FcRn colocalized in vivo with macrosialin (CD68) and Ncl-Macro, two macrophage markers, in the lamina propria of human small intestine. The heavy chain of FcRn was associated with the beta(2)-microglobulin (beta(2)m) light chain in U937 and THP-1 cells. FcRn bound human IgG at pH 6.0, but not at pH 7.5. This binding could be inhibited by human IgG Fc, but not Fab. FcRn could be detected on the cell surface of activated, but not resting, THP-1 cells. Furthermore, FcRn was uniformly present intracellularly in all blood monocytes and intestinal macrophages. FcRn was detectable on the cell surface of a significant fraction of monocytes at lower levels and on a small subset of tissue macrophages that expressed high levels of FcRn on the cell surface. These data show that FcRn is functionally expressed and its cellular distribution is regulated in monocytes, macrophages, and dendritic cells, suggesting that it may confer novel IgG binding functions upon these cell types relative to typical Fc gamma Rs: Fc gamma RI, Fc gamma RII, and Fc gamma RIII. PMID- 11207284 TI - Immature multipotent hemopoietic progenitors lacking long-term bone marrow reconstituting activity in the aorta-gonad-mesonephros region of murine day 10 fetuses. AB - Previous studies indicated that multipotent progenitors exist in early fetuses that do not contain long-term reconstituting (LTR) activity. However, it remained unclear whether these multipotent progenitors are committed to the hemopoietic lineage or are immature mesodermal cells or hemangioblasts. In this study, we have succeeded in enriching the multipotent progenitors that are capable of generating myeloid, T, and B cells in the LFA-1(-) subpopulation of TER-119(-)c kit(+)CD45(+) cells from the aorta-gonad-mesonephros (AGM) region of day 10 fetuses. We found that these day 10 AGM LFA-1(-) cells do not show the LTR activity, whereas day 11 AGM LFA-1(-) cells do have such an activity. These results strongly suggest that multipotent progenitors lacking LTR activity emerge as CD45(+) hemopoietic progenitor cells in the AGM region on the 10th day of gestation, and such p-Multi mature into hemopoietic stem cells by acquiring LTR activity. PMID- 11207285 TI - Modes of salmonid MHC class I and II evolution differ from the primate paradigm. AB - Rainbow trout (Oncorhynchus mykiss) and brown trout (Salmo trutta) represent two salmonid genera separated for 15--20 million years. cDNA sequences were determined for the classical MHC class I heavy chain gene UBA and the MHC class II beta-chain gene DAB from 15 rainbow and 10 brown trout. Both genes are highly polymorphic in both species and diploid in expression. The MHC class I alleles comprise several highly divergent lineages that are represented in both species and predate genera separation. The class II alleles are less divergent, highly species specific, and probably arose after genera separation. The striking difference in salmonid MHC class I and class II evolution contrasts with the situation in primates, where lineages of class II alleles have been sustained over longer periods of time relative to class I lineages. The difference may arise because salmonid MHC class I and II genes are not linked, whereas in mammals they are closely linked. A prevalent mechanism for evolving new MHC class I alleles in salmonids is recombination in intron II that shuffles alpha 1 and alpha 2 domains into different combinations. PMID- 11207286 TI - Association of mouse mammary tumor virus superantigen with MHC class II during biosynthesis. AB - Mouse mammary tumor viruses encode superantigens that interact with MHC class II proteins and stimulate T cells. We show here that presentation of mouse mammary tumor virus superantigen does not require DM. Furthermore, we have identified a strong class II peptide binding motif in the Mtv-7 superantigen, and we show that this motif is necessary for association with class II molecules in in vitro translation and in vivo functional assays. Our results suggest that endogenously synthesized viral superantigen can bind to MHC class II heterodimers during biosynthesis in the endoplasmic reticulum in a manner analogous to that used by the class II-associated invariant chain. PMID- 11207287 TI - Novel control motif cluster in the IgH delta-gamma 3 interval exhibits B cell specific enhancer function in early development. AB - The majority of the human Ig heavy chain (IgH) constant (C) region locus has been cloned and mapped. An exception is the region between C delta and C gamma 3, which is unstable and may be a recombination hot spot. We isolated a pBAC clone (pHuIgH3'delta-gamma 3) that established a 52-kb distance between C delta and C gamma 3. Sequence analysis identified a high number of repeat elements, explaining the instability of the region, and an unusually large accumulation of transcription factor-binding motifs, for both lymphocyte-specific and ubiquitous transcription activators (IKAROS, E47, Oct-1, USF, Myc/Max), and for factors that may repress transcription (Delta EF1, Gfi-1, E4BP4, C/EBP beta). Functional analysis in reporter gene assays revealed the importance of the C delta-C gamma 3 interval in lymphocyte differentiation and identified independent regions capable of either enhancement or silencing of reporter gene expression and interaction with the IgH intron enhancer E mu. In transgenic mice, carrying a construct that links the beta-globin reporter to the novel delta-gamma 3 intron enhancer (E delta-gamma 3), transgene transcription is exclusively found in bone marrow B cells from the early stage when IgH rearrangement is initiated up to the successful completion of H and L locus recombination, resulting in Ab expression. These findings suggest that the C delta-C gamma 3 interval exerts regulatory control on Ig gene activation and expression during early lymphoid development. PMID- 11207288 TI - At least one class I gene in restriction fragment pattern-Y (Rfp-Y), the second MHC gene cluster in the chicken, is transcribed, polymorphic, and shows divergent specialization in antigen binding region. AB - MHC genes in the chicken are arranged into two genetically independent clusters located on the same chromosome. These are the classical B: system and restriction fragment pattern-Y (Rfp-Y), a second cluster of MHC genes identified recently through DNA hybridization. Because small numbers of MHC class I and class II genes are present in both B: and Rfp-Y, the two clusters might be the result of duplication of an entire chromosomal segment. We subcloned, sequenced, and analyzed the expression of two class I loci mapping to Rfp-Y to determine whether Rfp-Y should be considered either as a second, classical MHC or as a region containing specialized MHC-like genes, such as class Ib genes. The Rfp-Y genes are highly similar to each other (93%) and to classical class Ia genes (73% with chicken B: class I; 49% with HLA-A). One locus is disrupted and unexpressed. The other, YFV, is widely transcribed and polymorphic. Mature YFV protein associated with beta(2)m arrives on the surface of chicken B (RP9) lymphoma cells expressing YFV as an epitope-tagged transgene. Substitutions in the YFV Ag-binding region (ABR) occur at four of the eight highly conserved residues that are essential for binding of peptide-Ag in the class Ia molecules. Therefore, it is unlikely that Ag is bound in the YFV ABR in the manner typical of class Ia molecules. This ABR specialization indicates that even though YFV is polymorphic and widely transcribed, it is, in fact, a class Ib gene, and Rfp-Y is a region containing MHC genes of specialized function. PMID- 11207289 TI - Gorillas with spondyloarthropathies express an MHC class I molecule with only limited sequence similarity to HLA-B27 that binds peptides with arginine at P2. AB - The human MHC class I gene, HLA-B27, is a strong risk factor for susceptibility to a group of disorders termed spondyloarthropathies (SpAs). HLA-B27-transgenic rodents develop SpAs, implicating HLA-B27 in the etiology of these disorders. Several nonhuman primates, including gorillas, develop signs of SpAs indistinguishable from clinical signs of humans with SpAs. To determine whether SpAs in gorillas have a similar HLA-B27-related etiology, we analyzed the MHC class I molecules expressed in four affected gorillas. Gogo-B01, isolated from three of the animals, has only limited similarity to HLA-B27 at the end of the alpha1 domain. It differs by several residues in the B pocket, including differences at positions 45 and 67. However, the molecular model of Gogo-B*0101 is consistent with a requirement for positively charged residues at the second amino acid of peptides bound by the MHC class I molecule. Indeed, the peptide binding motif and sequence of individual ligands eluted from Gogo-B*0101 demonstrate that, like HLA-B27, this gorilla MHC class I molecule binds peptides with arginine at the second amino acid position of peptides bound by the MHC class I molecule. Furthermore, live cell binding assays show that Gogo-B*0101 can bind HLA-B27 ligands. Therefore, although most gorillas that develop SpAs express an MHC class I molecule with striking differences to HLA-B27, this molecule binds peptides similar to those bound by HLA-B27. PMID- 11207290 TI - Structural and functional consequences of altering a peptide MHC anchor residue. AB - To better understand TCR discrimination of multiple ligands, we have analyzed the crystal structures of two Hb peptide/I-E(k) complexes that differ by only a single amino acid substitution at the P6 anchor position within the peptide (E73D). Detailed comparison of multiple independently determined structures at 1.9 A resolution reveals that removal of a single buried methylene group can alter a critical portion of the TCR recognition surface. Significant variance was observed in the peptide P5-P8 main chain as well as a rotamer difference at LeuP8, approximately 10 A distal from the substitution. No significant variations were observed in the conformation of the two MHC class II molecules. The ligand alteration results in two peptide/MHC complexes that generate bulk T cell responses that are distinct and essentially nonoverlapping. For the Hb-specific T cell 3.L2, substitution reduces the potency of the ligand 1000-fold. Soluble 3.L2 TCR binds the two peptide/MHC complexes with similar affinity, although with faster kinetics. These results highlight the role of subtle variations in MHC Ag presentation on T cell activation and signaling. PMID- 11207291 TI - Early recruitment of neutrophils determines subsequent T1/T2 host responses in a murine model of Legionella pneumophila pneumonia. AB - The contribution of neutrophils to lethal sensitivity and cytokine balance governing T1 and T2 host responses was assessed in a murine model of Legionella pneumophila pneumonia. Neutrophil depletion by administration of granulocyte specific mAb RB6-8C5 at 1 day before infection rendered mice approximately 100 fold more susceptible to lethal pneumonia induced by L. pneumophila. However, this treatment did not alter early bacterial clearance, despite a substantial decrease in neutrophil influx at this time point. Cytokine profiles in the lungs of control mice demonstrated strong T1 responses, characterized by an increase of IFN-gamma and IL-12. In contrast, neutrophil-depleted mice exhibited significantly lower levels of IFN-gamma and IL-12, and elevation of T2 cytokines, IL-4 and IL-10. Immunohistochemistry of bronchoalveolar lavage cells demonstrated the presence of IL-12 in neutrophils, but not alveolar macrophages. Moreover, IL 12 was detected in lavage cell lysates by ELISA, which was paralleled to neutrophil number. However, intratracheal administration of recombinant murine IL 12 did not restore resistance, whereas reconstitution of IFN-gamma drastically improved bacterial clearance and survival in neutrophil-depleted mice. Taken together, these data demonstrated that neutrophils play crucial roles in primary L. pneumophila infection, not via direct killing but more immunomodulatory effects. Our results suggest that the early recruitment of neutrophils may contribute to T1 polarization in a murine model of L. pneumophila pneumonia. PMID- 11207292 TI - Impaired pulmonary host defense in mice lacking expression of the CXC chemokine lungkine. AB - Lungkine (CXCL15) is a novel CXC chemokine that is highly expressed in the adult mouse lung. To determine the biologic function of Lungkine, we generated Lungkine null mice by targeted gene disruption. These mice did not differ from wild-type mice in their hematocrits or in the relative number of cells in leukocyte populations of peripheral blood or other tissues, including lung and bone marrow. However, Lungkine null mice were more susceptible to Klebsiella pneumonia infection, with a decreased survival and increased lung bacterial burden compared with infected wild-type mice. Histologic analysis of the lung and assessment of leukocytes in the bronchioalveolar lavage revealed that neutrophil numbers were normal in the lung parenchyma, but reduced in the airspace. The production of other neutrophil chemoattractants in the Lungkine null mice did not differ from that in wild-type mice, and neutrophil migration into other tissues was normal. Taken together, these findings demonstrate that Lungkine is an important mediator of neutrophil migration from the lung parenchyma into the airspace. PMID- 11207293 TI - Hypercholesterolemia exacerbates virus-induced immunopathologic liver disease via suppression of antiviral cytotoxic T cell responses. AB - The immune system has to be optimally balanced to be highly effective against infections with cytopathic microbial pathogens and must guarantee efficient destruction of cells infected with noncytopathic agents while leaving the integrity of noninfected cells largely unaltered. We describe here the effects of genetically induced hypercholesterolemia on cellular immunity in apolipoprotein E (ApoE(-/-)) and low density lipoprotein receptor-deficient (LDLR(-/-)) mice during infection with the hepatotropic lymphocytic choriomeningitis virus WE strain. In both ApoE(-/-) and LDLR(-/-) mice hypercholesterolemia aggravated virus-induced immunopathologic liver disease. ApoE(-/-) mice exhibited a higher susceptibility to virus-induced immunopathology than LDLR(-/-) mice and usually succumbed to immunopathologic disease when infected with high doses of virus. Initial virus spread was not influenced by the hypercholesterolemia, whereas clearance of the virus from spleen and nonlymphoid organs, including liver, was delayed. Activation of antiviral CTL, measured by ex vivo cytotoxicity and IFN gamma production, and recruitment of specific CTL into blood and liver were impaired in hypercholesterolemic mice, indicating that hypercholesterolemia had a significant suppressive effect on cellular immunity. Taken together, these data provide evidence that hypercholesterolemia suppresses antiviral immune responses, thereby changing the host-virus balance, and can increase susceptibility to acute or chronic and potentially lethal virus-induced immunopathologic disease. These findings impinge on our understanding of hypercholesterolemia as a disease parameter and may explain aspects of the frequent association of persistent pathogens with hypercholesterolemia-induced diseases, such as atherosclerosis. PMID- 11207294 TI - Soluble CD16 inhibits CR3 (CD11b/CD18)-mediated infection of monocytes/macrophages by opsonized primary R5 HIV-1. AB - We demonstrate that soluble CD16 (sCD16; soluble Fc gamma RIII), a natural ligand of CR3, inhibits the infection of monocytes by primary R5 HIV-1 strain opsonized with serum of seronegative individuals. Inhibition of monocyte infection by sCD16 was similar to that observed with anti-CR3 mAbs, indicating that opsonized HIV may use a CR3-dependent pathway for entry in monocytic cells. Cultured human monocytes express both CR3 (CD11b/CD18) and CCR5 receptors. RANTES, the natural ligand of CCR5, inhibited infection of monocytes with unopsonized HIV particles and partially that of monocytes infected with HIV particles opsonized with complement-derived fragments. Although HIV-infected monocytes from homozygous CCR5 Delta 32/Delta 32 (CCR5(-/-)) individuals produce low levels of p24, cells infected with opsonized particles produced higher levels of p24 than cells infected with unopsonized particles. Our results thus suggest that CR3 may represent an alternative coreceptor to CCR5 of opsonized primary R5 virus entry into monocytes/macrophages. We also observed that the concentration of sCD16 is greatly decreased in sera of HIV-infected patients with low lymphocyte CD4(+) counts. Taken together, our findings suggest that sCD16, present in plasma, may play an important role in controlling HIV-1 spread. PMID- 11207295 TI - Depletion of CD4+ T cells precipitates immunopathology in immunodeficient mice infected with a noncytocidal virus. AB - IFN-gamma-deficient (IFN-gamma(-/-)) mice inoculated with intermediate doses of a slowly replicating strain of lymphocytic choriomeningitis virus become chronically infected. In such mice a hypercompensated CTL response is observed that partially controls virus replication. Here we have investigated whether CD4(+) Th cells are required to establish and maintain this new equilibrium. The absence of IFN-gamma does not impair the generation of IL-2-producing CD4(+) cells, and depletion of these cells precipitates severe CD8(+) T cell-mediated immunopathology in IFN-gamma(-/-) mice, indicating an important role of CD4(+) T cells in preventing this syndrome. Analysis of organ virus levels revealed a further impairment of virus control in IFN-gamma(-/-) mice following CD4(+) cell depletion. Initially the antiviral CTL response did not require CD4(+) cells, but with time an impaired reactivity toward especially the glycoprotein 33--41 epitope was noted. Enumeration of epitope-specific (glycoprotein 33--41 and nucleoprotein 396--404) CD8(+) T cells by use of tetramers gave similar results. Finally, limiting dilution analysis of CTL precursors reveal an impaired capacity to sustain this population in CD4(+)-depleted mice, especially in mice also deficient in IFN-gamma. Thus, our findings disclose that T cell help is required to sustain the expanded CTL precursor pool required in IFN-gamma(-/-) mice. This interpretation is supported by mathematical modeling that predicts an increased requirement for help in IFN-gamma(-/-) hosts similar to what is found with fast replicating virus strains in normal hosts. Thus, the functional integrity of CD8(+) effector T cells is one important factor influencing the requirement for T cell help during viral infection. PMID- 11207296 TI - Mycobacterium tuberculosis phagosomes exhibit altered calmodulin-dependent signal transduction: contribution to inhibition of phagosome-lysosome fusion and intracellular survival in human macrophages. AB - Mycobacterium tuberculosis successfully parasitizes macrophages by disrupting the maturation of its phagosome, creating an intracellular compartment with endosomal rather than lysosomal characteristics. We have recently demonstrated that live M. tuberculosis infect human macrophages in the absence of an increase in cytosolic Ca(2+) ([Ca(2+)](c)), which correlates with inhibition of phagosome-lysosome fusion and intracellular viability. In contrast, killed M. tuberculosis induces an elevation in [Ca(2+)](c) that is coupled to phagosome-lysosome fusion. We tested the hypothesis that defective activation of the Ca(2+)-dependent effector proteins calmodulin (CaM) and CaM-dependent protein kinase II (CaMKII) contributes to the intracellular pathogenesis of tuberculosis. Phagosomes containing live M. tuberculosis exhibited decreased levels of CaM and the activated form of CaMKII compared with phagosomes encompassing killed tubercle bacilli. Furthermore, ionophore-induced elevations in [Ca(2+)](c) resulted in recruitment of CaM and activation of CaMKII on phagosomes containing live M. tuberculosis. Specific inhibitors of CaM or CaMKII blocked Ca(2+) ionophore induced phagosomal maturation and enhanced the bacilli's intracellular viability. These results demonstrate a novel role for CaM and CaMKII in the regulation of phagosome-lysosome fusion and suggest that defective activation of these Ca(2+) activated signaling components contributes to the successful parasitism of human macrophages by M. tuberculosis. PMID- 11207297 TI - Organ-specific regulation of the CD8 T cell response to Listeria monocytogenes infection. AB - The intestinal mucosal CD8 T cell response to infection with Listeria monocytogenes was measured using MHC class I tetramers and was compared with the response in peripheral blood, secondary lymphoid tissue, and liver. To assess the vaccination potential of Listeria and to analyze responses in C57BL/6 mouse strains, a recombinant Listeria expressing OVA (rLM-ova) was generated. The response peaked at 9 days postinfection with a much larger fraction of the intestinal mucosa and liver CD8 T cell pool OVA specific, as compared with the spleen. However, these differences were not linked to bacterial titers in each site. The higher responses in lamina propria and liver resulted in a larger CD8 memory population in these tissues. Furthermore, the level of memory induced was dependent on infectious dose and inversely correlated with the magnitude of the recall response after oral challenge. Recall responses in the tissues were most robust in the lamina propria and liver, and reactivated Ag-specific T cells produced IFN-gamma. Infection of CD40- or MHC class II-deficient mice induced poor CD8 T cell responses in the intestinal mucosa, but only partially reduced responses in the spleen and liver. Overall, the results point to novel pathways of tissue-specific regulation of primary and memory antimicrobial CD8 T cell responses. PMID- 11207298 TI - C5a and C5a(desArg) enhance the susceptibility of monocyte-derived macrophages to HIV infection. AB - Mononuclear phagocytes, which include circulating blood monocytes and differentiated tissue macrophages, are believed to play a central role in the sexual transmission of HIV infection. The ability of HIV to productively infect these cells may be influenced by action of exogenous or host-derived substances at the site of viral entry. Given the potent capacities of inflammatory mediators to stimulate anaphylatoxic and immunomodulatory functions in mucosa, the effects of complement-derived anaphylatoxins on the susceptibility of monocytes and monocyte-derived macrophages (MDM) to HIV-1 infection were examined. In our in vitro system, the susceptibility to infection was up to 40 times increased in MDM that had been exposed to C5a or C5a(desArg), but not to C3a or C3a(desArg), for 2 days before adding of virus. By contrast, the treatment with complement anaphylatoxins did not affect HIV replication in fresh monocytes. Stimulatory effect of C5a and its desArg derivative on HIV infection correlated with the increase of TNF-alpha and IL-6 secretion from MDM. All these functional effects of C5a and C5a(desArg) were reversible by treatment of cells with the mAb that functionally blocks C5aR. Taken together, these results indicate that C5a and C5a(desArg) may increase the susceptibility of MDM to HIV infection through stimulation of TNF-alpha and IL-6 secretion from these cells. PMID- 11207299 TI - General suppression of macrophage gene expression during Leishmania donovani infection. AB - Within the mammalian host, Leishmania donovani is an obligatory intracellular protozoan that resides and multiplies exclusively in the phagolysosomes of macrophages. The outcome of this infection is governed by the interaction between Leishmania and macrophage molecules that ultimately effect the expression of genes within both cells. To explore the effect of this intracellular infection on macrophage gene expression, a cDNA expression array analysis was performed to compare gene expression profiles in noninfected and L. donovani-infected macrophages. In this manner, it was possible to examine the effect of infection on the expression of several hundred well-characterized host cell genes in an unbiased manner. Interestingly, approximately 40% of the genes whose expression was detected in macrophages were down-regulated during infection with L. donovani. However, several genes were also induced during the infection process, some of which could play a role in recruitment of additional macrophages to the site of infection. Taken together, the general suppression of gene expression in addition to the selective induction of key genes is likely to play an important role in allowing the parasite to survive and proliferate within its host macrophage cell. PMID- 11207300 TI - Requirement of mitogen-activated protein kinases and I kappa B phosphorylation for induction of proinflammatory cytokines synthesis by macrophages indicates functional similarity of receptors triggered by glycosylphosphatidylinositol anchors from parasitic protozoa and bacterial lipopolysaccharide. AB - In the present study, we evaluated the ability of GPI-anchored mucin-like glycoproteins purified from Trypanosoma cruzi trypomastigotes (tGPI-mucin) to trigger phosphorylation of different mitogen-activated protein kinases (MAPKs) and related transcription factors in inflammatory macrophages. Kinetic experiments show that the peak of extracellular signal-related kinase (ERK)-1/ERK 2, stress-activated protein kinase (SAPK) kinase-1/mitogen-activated protein kinase (MAPK) kinase-4, and p38/SAPK-2, phosphorylation occurs between 15 and 30 min after macrophage stimulation with tGPI-mucin or GPI anchors highly purified from tGPI-mucins (tGPI). The use of the specific inhibitors of ERK-1/ERK-2 (PD 98059) and p38/SAPK-2 (SB 203580) phosphorylation also indicates the role of MAPKs, with possible involvement of cAMP response element binding protein, in triggering TNF-alpha and IL-12 synthesis by IFN-gamma-primed-macrophages exposed to tGPI or tGPI-mucin. In addition, tGPI-mucin and tGPI were able to induce phosphorylation of I kappa B, and the use of SN50 peptide, an inhibitor of NF kappa B translocation, resulted in 70% of TNF-alpha synthesis by macrophages exposed to tGPI-mucin. Finally, the similarity of patterns of MAPK and I kappa B phosphorylation, the concentration of drugs required to inhibit cytokine synthesis, as well as cross-tolerization exhibited by macrophages exposed to tGPI, tGPI-mucin, or bacterial LPS, suggest that receptors with the same functional properties are triggered by these different microbial glycoconjugates. PMID- 11207301 TI - Contribution of Th1 and Th2 cells to protection and pathology in experimental models of granulomatous lung disease. AB - Mice that had received adoptive transfer of DO11.10 TCR transgenic T cells polarized toward a Th1 or a Th2 phenotype were challenged with Ag-coated beads or with recombinant Mycobacterium tuberculosis expressing the OVA determinant. The resulting bead-induced pulmonary granulomas reflected the phenotype of the adoptively transferred T cells, with the Th2 cells promoting a fibrotic reaction. Mice receiving Th1 cells mounted an epitope-specific protective response to challenge with recombinant M. tuberculosis. Th2 recipients were characterized by enhanced weight loss and lung fibrosis during acute high-dose infection. The combination of TCR transgenic T cells and epitope-tagged mycobacteria provides a novel experimental model for investigation of the pathogenesis of tuberculosis. PMID- 11207302 TI - Prophylactic tumor vaccination: comparison of effector mechanisms initiated by protein versus DNA vaccination. AB - Clinical success in tumor vaccination frequently does not reach expectation. Since vaccination protocols are quite variable, we used the murine renal cell carcinoma line RENCA transfected with the lacZ gene (RENCA-beta-gal) to compare the efficacy of two different vaccination strategies or their combination and to elaborate on the underlying mechanisms. BALB/c mice were vaccinated either with naked lacZ DNA or with attenuated Salmonella typhimurium transformed with lacZ DNA or with dendritic cells (DC) loaded with the beta-galactosidase protein or mice were vaccinated with both DNA and protein. Although all regimens led to a prolongation of survival time, oral vaccination with transfected S. typhimurium followed by i.v. transfer of protein-loaded DC provided the optimal schedule. In this setting, >50% of mice remained tumor free after challenge with 10 times the lethal tumor dose of RENCA-beta-gal. As explored in transfer experiments, the superior efficacy of combining DNA and protein vaccination is due to the facts that 1) optimal protection depends on both activated CD4(+) and CD8(+) cells and 2) CD8(+) CTL are most strongly activated by vaccination with transformed Salmonella, whereas vaccination with protein-loaded DC is superior for the activation of Th. The latter induced sustained activation of CTL and recruitment of nonadaptive defense mechanisms. The data demonstrate the strength of DNA vaccination, particularly by the oral route, and provide evidence that a combined treatment with protein-loaded DC can significantly increase the therapeutic efficacy. PMID- 11207303 TI - Intranasal immunization with CpG oligodeoxynucleotides as an adjuvant dramatically increases IgA and protection against herpes simplex virus-2 in the genital tract. AB - Development of vaccines capable of preventing the transmission or limiting the severity of sexually transmitted viruses, such as HSV and HIV, will likely be dependent on the induction of potent long-lasting mucosal immune responses in the genital tract. Recently, synthetic oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs were shown to serve as potent adjuvants for the induction of mucosal immune responses. Here, we show that intranasal immunization with CpG ODN, plus recombinant glycoprotein B (rgB) of HSV-1, results in significantly elevated levels of specific anti-gB IgA Abs in vaginal washes that remained high throughout the estrous cycle. Additionally, dramatically elevated numbers of specific IgA Ab-secreting cells were present and persisted in the genital tract in response to intravaginal (IVAG) HSV-2 challenge. HSV-2-specific CTL were observed at moderate levels in the spleens of CpG or non-CpG ODN immunized mice. In contrast, strong CTL responses were observed locally in the genital tissues of both groups following IVAG HSV-2 challenge. Interestingly, mice immunized intranasally with rgB plus CpG ODN, but not non-CpG ODN, were significantly protected following IVAG HSV-2 challenge. Measurement of virus in protected CpG-immunized mice revealed a log lower level of replication within the first few days after infection. In conclusion, these results indicate that intranasal immunization with CpG ODN plus protein mediates immunity in the female genital tract capable of protecting against a sexually transmitted pathogen. PMID- 11207305 TI - Maturation versus death of developing double-positive thymocytes reflects competing effects on Bcl-2 expression and can be regulated by the intensity of CD28 costimulation. AB - Immature double-positive (DP) thymocytes mature into CD4(+)CD8(-) cells in response to coengagement of TCR with any of a variety of cell surface "coinducer" receptors, including CD2. In contrast, DP thymocytes are signaled to undergo apoptosis by coengagement of TCR with CD28 costimulatory receptors, but the molecular basis for DP thymocyte apoptosis by TCR plus CD28 coengagement is not known. In the present study, we report that TCR plus CD28 coengagement does not invariably induce DP thymocyte apoptosis but, depending on the intensity of CD28 costimulation, can induce DP thymocyte maturation. We demonstrate that distinct but interacting signal transduction pathways mediate DP thymocyte maturation signals and DP thymocyte apoptotic signals. Specifically, DP maturation signals are transduced by the extracellular signal-related kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway and up-regulate expression of the antiapoptotic protein Bcl-2. In contrast, the apoptotic response stimulated by CD28 costimulatory signals is mediated by ERK/MAPK-independent pathways. Importantly, when TCR-activated thymocytes are simultaneously coengaged by both CD28 and CD2 receptors, CD28 signals can inhibit ERK/MAPK-dependent Bcl-2 protein up regulation. Thus, there is cross-talk between the signal transduction pathways that transduce apoptotic and maturation responses, enabling CD28-initiated signal transduction pathways to both stimulate DP thymocyte apoptosis and also negatively regulate maturation responses initiated by TCR plus CD2 coengagement. PMID- 11207304 TI - Fas/Fas ligand pathway, apoptosis, and clonal anergy involved in systemic acetylcholine receptor T cell epitope tolerance. AB - The cellular mechanisms of high dose systemic acetylcholine receptor (AChR) T cell epitope, alpha 146--162 peptide-induced tolerance in experimental myasthenia gravis were examined. CD4 cells are the prime target for alpha 146--162 peptide induced tolerance. The expression of CD69, Fas, and B7.2 molecules on AChR-immune lymphocytes was enhanced within 4--12 h after tolerance induction. A high dose of alpha 146--162 peptide in IFA failed to suppress T cell proliferation and/or clinical myasthenia gravis in lpr and gld mice deficient in Fas and Fas ligand, respectively. A high dose of alpha 146--162 peptide in IFA in AChR-immunized mice induced apoptosis of BV6 cells. Further, reconstitution of IL-2 in vitro recovered alpha 146--162 peptide tolerized T cell proliferation, IFN-gamma, and IL-10 production. The findings implicate the possible role of Fas-/Fas ligand mediated apoptosis and the resulting clonal anergy as the mechanisms of high dose AChR alpha 146--162 peptide-induced tolerance on CD4 cells. PMID- 11207306 TI - Promotion of neutrophil apoptosis by TNF-alpha. AB - We examined the ability of TNF-alpha to modulate human neutrophil apoptosis. Neutrophils cultured with TNF-alpha alone undergo a low but significant increase in the number of apoptotic cells. More interestingly, when neutrophils were pretreated with TNF-alpha for 1-2 min at 37 degrees C and then were exposed to a variety of agents such as immobilized IgG, IgG-coated erythrocytes, complement treated erythrocytes, zymosan, PMA, zymosan-activated serum, fMLP, Escherichia coli, and GM-CSF for 3 h at 37 degrees C, a marked stimulation of apoptosis was observed. Similar results were obtained in neutrophils pretreated with TNF-alpha for 30 min, 1 h, 3 h, and 18 h. Dose-dependent studies showed that TNF-alpha enhances neutrophil apoptosis at concentrations ranging from 1 to 100 ng/ml. In contrast to the observations made in neutrophils pretreated with TNF-alpha, there was no stimulation of apoptosis when TNF-alpha was added to neutrophils previously activated by conventional agonists. Experiments performed to establish the mechanism through which TNF-alpha promotes neutrophil apoptosis showed that neither reactive oxygen intermediates nor the Fas/Fas ligand system appear to be involved. Our results suggest that TNF-alpha plays a critical role in the control of neutrophil survival by virtue of its ability to induce an apoptotic death program which could be triggered by a variety of conventional agonists. PMID- 11207307 TI - Differential effects of CD18, CD29, and CD49 integrin subunit inhibition on neutrophil migration in pulmonary inflammation. AB - Neutrophil migration to lung alveoli is a characteristic of lung diseases and is thought to occur primarily via capillaries rather than postcapillary venules. The role of adhesion molecules CD18 and CD29 on this migration in a mouse model of lung inflammation has been investigated. The number of neutrophils present in bronchoalveolar lavage fluid was determined 4 h after intratracheal instillation of LPS (0.1-1 microg) or murine recombinant KC (CXC chemokine, 0.03-0.3 microg). Both stimuli produced a dose-related increase in neutrophil accumulation. Intravenous anti-mouse CD18 mAb, 2E6 (0.5 mg/mouse), significantly (p < 0.001) attenuated LPS (0.3 microg)- but not KC (0.3 microg)-induced neutrophil accumulation. The anti-mouse CD29 mAb, HM beta 1-1 (0.02 mg/mouse), significantly (p < 0.05) inhibited both LPS (0.3 microg)- and KC (0.3 microg)-induced neutrophil migration. A second mAb to CD18 (GAME-46) and both F(ab')(2) and Fab of HM beta 1-1 produced similar results to those above, while coadministration of mAbs did not result in greater inhibition. Electron microscopy studies showed that CD29 was involved in the movement of neutrophils from the interstitium into alveoli. The effect of mAbs to CD49 (alpha integrin) subunits of CD29 was also examined. mAbs to CD49e and CD49f inhibited both responses, while anti-CD49b and CD49d significantly inhibited responses to KC only. These data suggest that CD29 plays a critical role in neutrophil migration in pulmonary inflammation and that CD49b and CD49d mediate CD18-independent neutrophil accumulation. PMID- 11207309 TI - Effective treatment of established murine collagen-induced arthritis by systemic administration of dendritic cells genetically modified to express IL-4. AB - Dendritic cells (DC) are APCs that are able to stimulate or inhibit immune responses, depending on levels of expression of MHC class I and II costimulatory molecules and cytokines. Our previous studies have suggested that the observed contralateral effect, where injection of a vector carrying certain immunomodulatory genes into one joint resulted in inhibition of arthritis in untreated joints, is mediated by in vivo modification of DC. Therefore, we have examined the ability of genetically modified DC to suppress established murine collagen-induced arthritis (CIA) after i.v. delivery. IL-4 has been shown to partially reduce the severity of CIA after repeated injection of recombinant protein or by injection of an adenoviral vector expressing IL-4. Here we demonstrate that i.v. injection of immature DC, infected with an adenoviral vector expressing IL-4, into mice with established CIA resulted in almost complete suppression of disease, with no recurrence for up to 4 wk posttreatment. Injection i.v. of fluorescently labeled DC demonstrated that the cells rapidly migrated to the liver and spleen after 6 h and to the lymph nodes by 24 h. In culture, spleen cells from DC/IL-4-treated mice produced less IFN-gamma after stimulation by collagen than did control groups. In addition, DC/IL-4 administration decreased the level of specific Abs against type II collagen, in particular the IgG2 Th1 isotype 14 days posttreatment. These results demonstrate the ability to treat effectively established murine arthritis by systemic administration of DC expressing IL-4. PMID- 11207308 TI - Oncostatin M-induced matrix metalloproteinase and tissue inhibitor of metalloproteinase-3 genes expression in chondrocytes requires Janus kinase/STAT signaling pathway. AB - Oncostatin M (OSM), a member of the IL-6 superfamily of cytokines, is elevated in patients with rheumatoid arthritis and, in synergy with IL-1, promotes cartilage degeneration by matrix metalloproteinases (MMPs). We have previously shown that OSM induces MMP and tissue inhibitor of metalloproteinase-3 (TIMP-3) gene expression in chondrocytes by protein tyrosine kinase-dependent mechanisms. In the present study, we investigated signaling pathways regulating the induction of MMP and TIMP-3 genes by OSM. We demonstrate that OSM rapidly stimulated phosphorylation of Janus kinase (JAK) 1, JAK2, JAK3, and STAT1 as well as extracellular signal-regulated kinase (ERK) 1/2, p38, and c-Jun N-terminal kinase 1/2 mitogen-activated protein kinases in primary bovine and human chondrocytes. A JAK3-specific inhibitor blocked OSM-stimulated STAT1 tyrosine phosphorylation, DNA-binding activity of STAT1 as well as collagenase-1 (MMP-1), stromelysin-1 (MMP-3), collagenase-3 (MMP-13), and TIMP-3 RNA expression. In contrast, a JAK2 specific inhibitor, AG490, had no impact on these events. OSM-induced ERK1/2 activation was also not affected by these inhibitors. Similarly, curcumin (diferuloylmethane), an anti-inflammatory agent, suppressed OSM-stimulated STAT1 phosphorylation, DNA-binding activity of STAT1, and c-Jun N-terminal kinase activation without affecting JAK1, JAK2, JAK3, ERK1/2, and p38 phosphorylation. Curcumin also inhibited OSM-induced MMP-1, MMP-3, MMP-13, and TIMP-3 gene expression. Thus, OSM induces MMP and TIMP-3 genes in chondrocytes by activating JAK/STAT and mitogen-activated protein kinase signaling cascades, and interference with these pathways may be a useful approach to block the catabolic actions of OSM. PMID- 11207310 TI - Integrin alpha E(CD103)beta 7 mediates adhesion to intestinal microvascular endothelial cell lines via an E-cadherin-independent interaction. AB - Integrins are important for T cell interactions with endothelial cells. Because the integrin alpha(E)beta(7) is expressed on some circulating gut-homing T cells and as T cell numbers are reduced in the intestinal lamina propria of alpha(E) deficient mice, we evaluated whether alpha(E)beta(7) mediates binding to intestinal endothelial cells. We found that anti-alpha(E)beta(7) mAbs partially blocked the binding of cultured intraepithelial T cells to human intestinal microvascular endothelial cells (HIMEC). Furthermore, alpha(E)beta(7)-transfected K562 cells bound more efficiently than vector-transfected K562 cells to HIMEC. Finally, HIMEC bound directly to an alpha(E)beta(7)-Fc fusion protein. These interactions were partially blocked by anti-alpha(E)beta(7) mAbs, and endothelial cell binding to the alpha(E)beta(7)-Fc was dependent upon the metal ion-dependent adhesion site within the alpha(E) A domain. Of note, the HIMEC lacked expression of E-cadherin, the only known alpha(E)beta(7) counterreceptor as assessed by functional studies, flow cytometry, and RT-PCR. Thus, HIMEC/alpha(E)beta(7) binding was independent of E-cadherin. In addition, this interaction appeared to be tissue selective, as HIMEC bound to the alpha(E)beta(7)-Fc, whereas microvascular endothelial cells from the skin did not. Finally, there was evidence for an alpha(E)beta(7) ligand on intestinal endothelial cells in vivo, as alpha(E)beta(7) expression enhanced lymphocyte binding around vessels in the lamina propria in tissue sections. Thus, we have defined a novel interaction for alpha(E)beta(7) at a nonepithelial location. These studies suggest a role for alpha(E)beta(7) in interactions with the intestinal endothelium that may have implications for intestinal T cell homing or functional responses. PMID- 11207311 TI - Extracellular signal-regulated kinase 1/2-mediated phosphorylation of cytosolic phospholipase A2 is essential for human eosinophil adhesion to fibronectin. AB - We examined the role of p38, p42, and p44 mitogen-activated protein kinase (MAPK) isoforms and cytosolic phospholipase A(2) (cPLA(2)) activation in human eosinophil adhesion to plate-coated fibronectin (FN). In the control state, eosinophil adhesion was maximal, with 10 microg/ml FN at 30 min, and decreased after 60-90 min. Western blot analysis demonstrated that p44/42 MAPK (extracellular signal-regulated kinase (ERK)1/2) and cPLA(2) were phosphorylated during adhesion to FN, whereas p38 MAPK phosphorylation was unchanged. Preincubation of eosinophils with U0126 or PD98059, two structurally unrelated MAPK kinase inhibitors, or arachidonic trifluoromethyl ketone, a cPLA(2) inhibitor, blocked eosinophil adhesion to FN. By contrast, eosinophil adhesion was unaffected by SB203580, a p38 MAPK inhibitor. Pretreatment of eosinophils with okadaic acid, a serine/threonine phosphatase inhibitor, at the concentrations that induced ERK1/2 and cPLA(2) phosphorylation caused an increase in maximal eosinophil adhesion to FN for >60 min. MAPK kinase inhibition but not p38 inhibition also blocked FN-mediated F-actin redistribution in eosinophils and prevented cPLA(2) phosphorylation caused by adhesion to FN. These results demonstrate that ERK1/2 mediating cPLA(2) activation is essential for eosinophil adhesion to FN. PMID- 11207312 TI - Oral administration of recombinant cholera toxin subunit B inhibits IL-12 mediated murine experimental (trinitrobenzene sulfonic acid) colitis. AB - Trinitrobenzene sulfonic acid (TNBS)-induced colitis is an IL-12-driven, Th1 T cell-mediated colitis that resembles human Crohn's disease. In the present study, we showed initially that the oral administration of recombinant subunit B of cholera toxin (rCT-B) at the time of TNBS-induced colitis by intrarectal TNBS instillation inhibits the development of colitis or, at later time when TNBS induced colitis is well established, brings about resolution of the colitis. Dose response studies showed that a majority of mice (68%) treated with rCT-B at a dose of 100 microg (times four daily doses) exhibited complete inhibition of the development of colitis, whereas a minority (30%) treated with rCT-B at a dose of 10 microg (times four daily doses) exhibited complete inhibition; in both cases, however, the remaining mice exhibited some reduction in the severity of inflammation. In further studies, we showed that rCT-B administration is accompanied by prevention/reversal of increased IFN-gamma secretion (the hallmark of a Th1 response) without at the same time causing an increase in IL-4 secretion. This decreased IFN-gamma secretion was not associated with the up regulation of the secretion of counterregulatory cytokines (IL-10 or TGF-beta), but was associated with a marked inhibition of IL-12 secretion, i.e., the secretion of the cytokine driving the Th1 response. Finally, we showed that rCT-B administration results in increased apoptosis of lamina propria cells, an effect previously shown to be indicative of IL-12 deprivation. From these studies, rCT-B emerges as a powerful inhibitor of Th1 T cell-driven inflammation that can conceivably be applied to the treatment of Crohn's disease. PMID- 11207313 TI - Role of nitric oxide synthase type 2 in acute infection with murine cytomegalovirus. AB - Whether or not NO plays a critical role in murine CMV (MCMV) infection has yet to be elucidated. In this study, we examined the role of NO in acute infection with MCMV using NO synthase type 2 (NOS2)-deficient mice. NOS2(-/-) mice were more susceptible to lethal infection with MCMV than NOS2(+/+) mice and generated a much higher peak virus titer in the salivary gland after acute infection. A moderate increase in the MCMV titer was also observed in other organs of NOS2(-/ ) mice such as the spleen, lung, and liver. The immune responses to MCMV infection including NK cell cytotoxicity and CTL response in NOS2(-/-) mice were comparable with those of NOS2(+/+) mice. Moreover, the ability to produce IFN gamma is not impaired in NOS2(-/-) mice after MCMV infection. The peritoneal macrophages from NOS2(-/-) mice, however, exhibited a lower antiviral activity than those from NOS2(+/+) mice, resulting in an enhanced viral replication in macrophages themselves. Treatment of these cells from NOS2(+/+) mice with a selective NOS2 inhibitor decreased the antiviral activity to a level below that obtained with NOS2(-/-) mice. In addition, the absence of NOS2 and NOS2-mediated antiviral activity of macrophages resulted in not only an enhanced MCMV replication and a high mortality but also a consequent risk of the latency. It was thus concluded that the NOS2-mediated antiviral activity of macrophages via NO plays a protective role against MCMV infection at an early and late stage of the infection. PMID- 11207314 TI - IL-13-induced airway hyperreactivity during respiratory syncytial virus infection is STAT6 dependent. AB - Airway damage and hyperreactivity induced during respiratory syncytial virus (RSV) infection can have a prolonged effect in infants and young children. These infections can alter the long-term function of the lung and may lead to severe asthma-like responses. In these studies, the role of IL-13 in inducing and maintaining a prolonged airway hyperreactivity response was examined using a mouse model of primary RSV infection. Using this model, there was evidence of significant airway epithelial cell damage and sloughing, along with mucus production. The airway hyperreactivity response was significantly increased by 8 days postinfection, peaked during days 10-12, and began to resolve by day 14. When the local production of Th1- and Th2-associated cytokines was examined, there was a significant increase, primarily in IL-13, as the viral response progressed. Treatment of RSV-infected mice with anti-IL-13 substantially inhibited airway hyperreactivity. Anti-IL-4 treatment had no effect on the RSV induced responses. Interestingly, when IL-13 was neutralized, an early increase in IL-12 production was observed within the lungs, as was a significantly lower level of viral Ags, suggesting that IL-13 may be regulating an important antiviral pathway. The examination of RSV-induced airway hyperreactivity in STAT6(-/-) mice demonstrated a significant attenuation of the response, similar to the anti-IL-13 treatment. In addition, STAT6(-/-) mice had a significant alteration of mucus-producing cells in the airway. Altogether, these studies suggest that a primary factor leading to chronic RSV-induced airway dysfunction may be the inappropriate production of IL-13. PMID- 11207315 TI - HLA-DP allele-specific T cell responses to beryllium account for DP-associated susceptibility to chronic beryllium disease. AB - Occupational exposure to small molecules, such as metals, is frequently associated with hypersensitivity reactions. Chronic beryllium (Be) disease (CBD) is a multisystem granulomatous disease that primarily affects the lung, and occurs in approximately 3% of individuals exposed to this element. Immunogenetic studies have demonstrated a strong association between CBD and possession of alleles of HLA-DP containing glutamic acid (Glu) at position 69 in the HLA-DP beta-chain. T cell clones were raised from three patients with CBD in whom exposure occurred 10 and 30 years previously. Of 25 Be-specific clones that were obtained, all were restricted by HLA-DP alleles with Glu at DP beta69. Furthermore, the proliferative responses of the clones were absolutely dependent upon DP beta Glu(69) in that a single amino acid substitution at this position abolished the response. As befits a disease whose pathogenesis involves a delayed type hypersensitivity response, the large majority of Be-specific clones secreted IFN-gamma (Th1) and little or no IL-4 (Th2) cytokines. This study provides insights into the molecular basis of DP2-associated susceptibility to CBD. PMID- 11207316 TI - CD40/CD40 ligand interactions are critical for elicitation of autoimmune-mediated fibrosis in the lung. AB - Pulmonary interstitial fibrosis (PIF), associated with persistent inflammation and increased collagen deposition in the interstitium, is often considered an autoimmune disease. Hapten immune PIF (HIPIF), a model for PIF, is elicited in the lung by a single intratracheal (i.t.) challenge in mice sensitized with hapten (2,4,6-trinitrobenzene sulfonic acid, TNBS). In this study, we characterized the role of CD40/CD40 ligand (CD40L) interactions in the elicitation of secondary cell-mediated immune responses that lead to development of fibrosis in the lung using an adoptive transfer model of HIPIF. The expression of CD40 was detected on bronchoalveolar lavage (BAL) cells 1-3 days after i.t. challenge with hapten in the HIPIF lung, but not lungs from the control mice. The CD40(bright) BAL cells morphologically resembled infiltrating monocytes. Furthermore, blocking CD40/CD40L interactions with blocking Ab decreased BAL production of Th1-mediators (IL-12 and TNF-alpha). Moreover, either blocking CD40/CD40L interactions with the Ab or using IL-12 knockout recipient mice prevented the increased collagen deposition (accumulation of hydroxyproline) in the lungs during HIPIF induction. We conclude that second signals (CD40/CD40L interactions) are required for elicitation of secondary immune responses that lead to PIF in vivo. The results support the notion that CD40/CD40L interactions are involved in the pathogenesis of an ongoing autoimmune disease. PMID- 11207317 TI - Immunosensitization of melanoma tumor cells to non-MHC Fas-mediated killing by MART-1-specific CTL cultures. AB - The discovery of human melanoma rejection Ags has allowed the rational design of immunotherapeutic strategies. One such Ag, MART-1, is expressed on >90% of human melanomas, and CTL generated against MART-1(27-35) kill most HLA A2.1(+) melanoma cells. However, variant tumor cells, which do not express MART-1, down-regulate MHC, or become resistant to apoptosis, will escape killing. Cytotoxic lymphocytes kill by two main mechanisms, the perforin/granzyme degranulation pathway and the TNF/Fas/TNF-related apoptosis-inducing ligand superfamily of apoptosis-inducing ligands. In this study, we examined whether cis-diaminedichloroplatinum (II) cisplatin (CDDP) sensitizes MART-1/HLA A2.1(+) melanoma and melanoma variant tumor cells to non-MHC-restricted, Fas ligand (FasL)-mediated killing by CTL. MART-1(27-35)-specific bulk CTL cultures were generated by pulsing normal PBL with MART-1(27-35) peptide. These CTL cultures specifically kill M202 melanoma cells (MART-1(+), HLA A2.1(+), FasR(-)), and MART-1(27-35) peptide-pulsed T2 cells (FasR(+)), but not M207 melanoma cells (MART-1(+), HLA A2.1(-), FasR(-)), FLU(58-66) peptide-pulsed T2 cells, or DU145 and PC-3 prostate cells (MART-1(-), HLA A2.1(-), FasR(+)). CDDP (0.1-10 microg/ml) sensitized non-MART-1(27-35) peptide-pulsed T2 to the CD8(+) subset of bulk MART-1-specific CTL, and killing was abolished by neutralizing anti-Fas Ab. Furthermore, CDDP up-regulated FasR expression and FasL-mediated killing of M202, and sensitized PC-3 and DU145 to killing by bulk MART-1-specific CTL cultures. These findings demonstrate that drug-mediated sensitization can potentiate FasL-mediated killing by MHC restricted CTL cell lines, independent of MHC and MART-1 expression on tumor cells. This represents a novel approach for potentially controlling tumor cell variants found in primary heterogeneous melanoma tumor cell populations that would normally escape killing by MART-1-specific immunotherapy. PMID- 11207318 TI - Gene expression of osteoclast differentiation factor is induced by lipopolysaccharide in mouse osteoblasts via Toll-like receptors. AB - Osteoclast differentiation factor (ODF), a recently identified cytokine of the TNF family, is expressed as a membrane-associated protein in osteoblasts and stromal cells. ODF stimulates the differentiation of osteoclast precursors into osteoclasts in the presence of M-CSF. Here we investigated the effects of LPS on the gene expression of ODF in mouse osteoblasts and an osteoblast cell line and found that LPS increased the ODF mRNA level. A specific inhibitor of extracellular signal-regulated kinase or protein kinase C inhibited this up regulation, indicating that extracellular signal-regulated kinase and protein kinase C activation was involved. A protein synthesis inhibitor, cycloheximide, rather enhanced the LPS-mediated increase of ODF mRNA, and both a neutralizing Ab of TNF-alpha and a specific inhibitor of PGE synthesis failed to block the ODF mRNA increase by native LPS. Thus, LPS directly induced ODF mRNA. Mouse osteoblasts and an osteoblast cell line constitutively expressed Toll-like receptor (TLR) 2 and 4, which are known as putative LPS receptors. ODF mRNA increases in response to synthetic lipid A were defective in primary osteoblasts from C3H/HeJ mice that contain a nonfunctional mutation in the TLR4 gene, suggesting that TLR4 plays an essential role in the process. Altogether, our results indicate that ODF gene expression is directly increased in osteoblasts by LPS treatment via TLR, and this pathway may play an important role in the pathogenesis of LPS-mediated bone disorders, such as periodontitis. PMID- 11207319 TI - Recombinant HIV-1 glycoprotein 120 induces distinct types of delayed hypersensitivity in persons with or without pre-existing immunologic memory. AB - Induction of T cell help is critical in HIV-1 control and potentially in prevention by immunization. A practical approach is needed to identify HIV-1 specific helper activities in vivo. We explored the feasibility of measuring delayed-type hypersensitivity (DTH) following intradermal injection of recombinant soluble HIV-1(MN) glycoprotein 120 in HIV-1-infected, vaccinated, and exposed individuals. DTH reactions were elicited within 48 h in 16 of 29 untreated, infected patients and in 24 of 30 uninfected vaccinees. Concomitant envelope-specific lymphoproliferation in vitro was undetectable among 9 infected patients tested with positive envelope-specific DTH. By contrast, no 48-h DTH reactions occurred among 25 high risk and 32 low risk, uninfected volunteers. However, 7--12 days after injection, 10 (40%) high risk and 11 (34%) low risk individuals developed induration resembling DTH, and the cellular infiltrates contained monocytes and T cells. Five of 18 examined also developed anti-gp120 Abs. The very delayed time course and lack of correlation with previous Ag exposure clearly distinguish this reaction from DTH. Thus, HIV-1 skin testing can identify persons with HIV-specific recall responses resulting from infection, in the absence of in vitro lymphoproliferation, and from vaccination. In contrast, very late reactivities may signify chemotactic properties of the envelope protein and/or herald the induction of primary HIV-specific Th1-type immunity. PMID- 11207320 TI - Characterization of hepatitis C virus core-specific immune responses primed in rhesus macaques by a nonclassical ISCOM vaccine. AB - Current therapies for the treatment of hepatitis C virus (HCV) infection are only effective in a restricted number of patients. Cellular immune responses, particularly those mediated by CD8(+) CTLs, are thought to play a role in the control of infection and the response to antiviral therapies. Because the Core protein is the most conserved HCV protein among genotypes, we evaluated the ability of a Core prototype vaccine to prime cellular immune responses in rhesus macaques. Since there are serious concerns about using a genetic vaccine encoding for Core, this vaccine was a nonclassical ISCOM formulation in which the Core protein was adsorbed onto (not entrapped within) the ISCOMATRIX, resulting in approximately 1-microm particulates (as opposed to 40 nm for classical ISCOM formulations). We report that this Core-ISCOM prototype vaccine primed strong CD4(+) and CD8(+) T cell responses. Using intracellular staining for cytokines, we show that in immunized animals 0.30-0.71 and 0.32-2.21% of the circulating CD8(+) and CD4(+) T cells, respectively, were specific for naturally processed HCV Core peptides. Furthermore, this vaccine elicited a Th0-type response and induced a high titer of Abs against Core and long-lived cellular immune responses. Finally, we provide evidence that Core-ISCOM could serve as an adjuvant for the HCV envelope protein E1E2. Thus, these data provide evidence that Core-ISCOM is effective at inducing cellular and humoral immune responses in nonhuman primates. PMID- 11207322 TI - Eukaryotic translation initiation factor-6 enhances histamine and IL-2 production in mast cells. AB - Eukaryotic translation initiation factor (eIF)-6 is known to be important in ribosome biogenesis. Previously, we have discovered that eIF-6 mRNA is induced in lung in a murine model of asthma. We also found that there was enhanced eIF-6 expression in mast cells stimulated with PMA plus calcium ionophore. Therefore, we hypothesized that the induction of eIF-6 enhances the production of bioactive mediators by mast cells upon allergic stimulation. In the current study, we found that eIF-6 mRNA was rapidly induced in murine mast cells stimulated by Fc epsilon RI cross-linking, which is a major physiologic stimulant for mast cells. eIF-6 was also induced in human mast cells upon stimulation. The increase in eIF-6 gene expression in murine mast cells was blocked by therapeutic agents such as dexamethasone and cyclosporin A. To determine the location and function of eIF-6, murine mast cells were transfected with a construct that overexpressed enhanced green fluorescent protein-tagged eIF-6. These experiments demonstrated that eIF-6 was localized predominantly in the nucleolus of the mast cells. Also, overexpression of enhanced green fluorescent protein/eIF-6 enhanced the production of histamine and IL-2, but not IL-4 by stimulated murine mast cells. These results suggest that eIF-6 regulates the production of selected bioactive mediators in allergic diseases. This is the first demonstration of a biologic function of eIF-6 in mammalian cells. PMID- 11207321 TI - IC14, an anti-CD14 antibody, inhibits endotoxin-mediated symptoms and inflammatory responses in humans. AB - CD14 is a receptor for cell wall components of Gram-negative and Gram-positive bacteria that has been implicated in the initiation of the inflammatory response to sepsis. To determine the role of CD14 in LPS-induced effects in humans, 16 healthy subjects received an i.v. injection of LPS (4 ng/kg) preceded (-2 h) by i.v. IC14, a recombinant chimeric mAb against human CD14, at a dose of 1 mg/kg over 1 h, or placebo. In subjects receiving IC14, saturation of CD14 on circulating monocytes and granulocytes was >90% at the time of LPS injection. IC14 attenuated LPS-induced clinical symptoms and strongly inhibited LPS-induced proinflammatory cytokine release, while only delaying the release of the anti inflammatory cytokines soluble TNF receptor type I and IL-1 receptor antagonist. IC14 also inhibited leukocyte activation, but more modestly reduced endothelial cell activation and the acute phase protein response. The capacity of circulating monocytes and granulocytes to phagocytose Escherichia coli was only marginally reduced after infusion of IC14. These data provide the first proof of principle that blockade of CD14 is associated with reduced LPS responsiveness in humans in vivo. PMID- 11207324 TI - Schizophrenia: what's under the microscope? PMID- 11207323 TI - Antigen-independent suppression of the allergic immune response to bee venom phospholipase A(2) by DNA vaccination in CBA/J mice. AB - Phospholipase A(2) (PLA(2)) is one of the major honey bee venom allergens for humans. To assess the long-term prevention of allergic reactions by DNA vaccination, a PLA(2)-CBA/J mouse model was employed using empty or PLA(2) sequence-carrying DNA plasmids. Early skin application of either DNA construct before (prophylactic approach) or after (therapeutic approach) sensitization with PLA(2)/alum led to reduced PLA(2)-specific IgE and IgG1 titers at 7 mo, with concomitant rise in IgG2a and IgG3. Splenocytes recovered at 5-6 mo after the last DNA administration exhibited a sustained IFN-gamma and IL-10 secretion and reduced IL-4 production. Recall challenge with PLA(2) boosted IFN-gamma and IL-10 secretion, suggesting the reactivation of quiescent memory Th1 lymphocytes. Mice from the prophylactic groups were fully protected against anaphylaxis, whereas 65% of the animals recovered in the therapeutic groups. Th1-polarized immune responses were also active in mice vaccinated with an empty plasmid 32 wk before sensitization with another Ag (OVA). This is the first demonstration that the Ag coding sequence in DNA vaccine is not necessary to promote immune modulation in naive and sensitized animals for a prolonged period, and has relevance for the understanding of the innate and induced mechanisms underlying gene immunotherapy in long-term treatment of allergy. PMID- 11207325 TI - Role of serotonin in the behavioral and psychological symptoms of dementia. AB - The behavioral and psychological symptoms of dementia (BPSD) can have serious debilitating effects on the patient and increase caregiver burden. Investigations into the underlying neuropathology indicate that the serotonergic system may contribute to BPSD. In addition, serotonergic pathways are known to interact extensively with the cholinergic, noradrenergic, GABAergic, and dopaminergic systems. Hence, serotonergic therapies may be used to manipulate other neurotransmitters systems to alleviate BPSD or in combination with agents specific for the other neurotransmitter receptor sites. Neurotransmitter modulated behaviors and evidence provided by pharmacological interventions are reviewed, focusing primarily on the serotonergic system. PMID- 11207326 TI - The lactic acid response to alkalosis in panic disorder : an integrative review. AB - Panic patients consistently show exaggerated lactic acid response to alkalosis, whether produced by hyperventilation or by sodium lactate infusion. Understanding why this occurs may provide important clues to the pathogenesis of panic disorder. Although brain hypoxia from excessive hypocapnia-induced cerebral vasoconstriction is often cited as the mechanism of elevated brain lactic acid in panic disorder, studies of brain metabolism show that hypocapnia rarely leads to brain hypoxia. Increased lactic acid production is a normal response to intracellular alkalosis and to intracellular cyclic AMP. Thus, other possible mechanisms of the exaggerated lactic acid response in panic disorder include a disturbance of mechanisms regulating intracellular pH and factors increasing intracellular cyclic AMP. Both mechanisms are consistent with the suffocation false alarm theory of panic disorder. This review suggests a theoretical framework for future magnetic resonance spectroscopy studies that can test some of the predictions of these competing models. PMID- 11207327 TI - Relationship between mood and motor fluctuations in Parkinson's disease. AB - Mood fluctuations have been reported in up to two-thirds of patients with Parkinson's disease who experience motor fluctuations. Most researchers indicate that mood fluctuations tend to be associated with motor fluctuations in that patients experience decreased mood when "off" (immobile) and elevated mood when "on" (mobile). Sixteen patients with Parkinson's disease and motor fluctuations completed hourly diaries for 7 consecutive days documenting their mood, anxiety, and motor states using visual analogue scales. Mood and anxiety fluctuations were frequently documented. Motor and emotional states were not, however, consistently correlated. When they were correlated, the most frequent pattern was the common occurrence of decreased mood, increased anxiety, and reduced motor function. PMID- 11207328 TI - Neuropsychiatric symptoms of patients with progressive supranuclear palsy and Parkinson's disease. AB - Neuropsychiatric symptoms are common in basal ganglia disorders and may have severe clinical consequences. The authors compared the neuropsychiatric manifestations of patients with Parkinson's disease (PD) and progressive supranuclear palsy (PSP). All 103 PD patients and 27 of the 61 PSP patients were taking dopaminergic agents. PSP patients showed significantly more apathy and disinhibition. Patients with PD had higher frequency of hallucinations, delusions, and depression. These results suggest that PSP patients show symptoms compatible with lesioned orbitofrontal and medial frontal circuits, such as disinhibition and apathy, whereas PD patients show symptoms associated with monoaminergic disturbances, such as psychosis and depression. PMID- 11207329 TI - The psychotic phenomenon in probable Alzheimer's disease: a positron emission tomography study. AB - Positron emission tomography was used to examine the mechanisms of the psychotic phenomenon in Alzheimer's disease (AD). Data from 2 patients with delusions and 2 with hallucinations were compared with those of 5 AD patients without psychosis. The patients with paranoid delusions had diminished relative regional cerebral blood flow (rel-CBF) in the left dorsolateral prefrontal and left medial temporal cortices. The patients with visual hallucinations showed diminished rel-CBF in the right parietal, left medial temporal, and left dorsolateral prefrontal cortices. These findings support the hypothesis that a frontal-temporal abnormality is associated with paranoid delusions in AD. By contrast, visual hallucinations are associated with parietal as well as frontal and temporal lobe dysfunction. In these patients, a left prefrontal-temporal cortex dysfunction appears to be a common denominator for the development of the psychotic phenomenon in AD. PMID- 11207330 TI - Psychiatric symptoms associated with cortical-subcortical dysfunction in Alzheimer's disease. AB - Positron emission tomography was used to evaluate 3 Alzheimer's disease (AD) patients: 1 with major depression, 1 with emotional lability, and 1 with apathy. Compared with 5 non-mood-disordered AD patients, the patient with depression had diminished relative regional cerebral blood flow (rel-CBF) in the anterior cingulate and superior temporal cortices, bilaterally. This patient also showed diminished rel-CBF in the left dorsolateral prefrontal and right medial temporal and parietal cortices. The patient with emotional lability had diminished rel-CBF in the anterior cingulate and dorsolateral prefrontal cortices, bilaterally, and left basal ganglia. The patient with apathy had diminished rel-CBF in the basal ganglia and dorsolateral prefrontal cortex, bilaterally. Results are consistent with the hypothesis of a common frontal-temporal-subcortical substrate (e.g., involving aminergic nuclei) in the etiology of depression in AD. Frontal subcortical dysfunction may also be associated with emotional lability and apathy in AD, although these may be related to a greater involvement of frontal-basal ganglia circuits. PMID- 11207331 TI - Risk factors in psychosis secondary to traumatic brain injury. AB - Psychosis is a rare but devastating sequela of traumatic brain injury (TBI). This study examined risk factors for developing a psychosis secondary to TBI (PSTBI). Demographics of 25 inpatients with PSTBI were statistically analyzed for risk factors. Data from the PSTBI group were also compared with data from a control group of TBI patients without psychosis. Results indicate the PSTBI group was more likely to have had a previous congenital neurological disorder or to have sustained a head injury prior to adolescence. The PSTBI also had a higher proportion of males. Discussion focuses on potential models for developing PSTBI. PMID- 11207332 TI - Personality disorder in multiple sclerosis correlates with cognitive impairment. AB - Previous studies of personality change in multiple sclerosis (MS) relied on brief, nonstandardized assessments or tests that are confounded with symptoms of acute psychiatric disorder. Objectives of the present study were to evaluate character change in MS by using comprehensive trait measures of personality and to determine if there is an association between personality change and cognitive dysfunction. Thirty-four MS patients and 14 healthy volunteers were studied. All underwent comprehensive neurologic and neuropsychologic evaluation. Personality assessments included both self and informant reports on the Hogan Empathy Scale and the NEO Personality Inventory. Abnormalities were found among MS patients indicating elevated neuroticism and reduction in empathy, agreeableness, and conscientiousness. Large patient/informant discrepancies were observed in the MS but not the control group. Three neuropsychological tests emphasizing executive control predicted the presence of these abnormalities; this association suggests a neurogenic, frontal lobe syndrome. PMID- 11207333 TI - An EEG severity index of traumatic brain injury. AB - EEG spectral analyses were conducted from 19 scalp locations for patients with mild (n=40), moderate (n=25), and severe (n=43) traumatic brain injury (TBI), 15 days to 4 years after injury. Severity of TBI was judged by emergency hospital admission records (Glasgow Coma Score and duration of coma and amnesia). Highest loading EEG variables on each factor that differed significantly between severe and mild TBI by univariate t-test were entered into a multivariate discriminant analysis, yielding 16 variables. Discriminant analysis between mild and severe TBI groups showed classification accuracy of 96.39%, sensitivity 95.45%, and specificity 97.44%. The EEG discriminant score also measured intermediate severity in moderate TBI patients. Results were cross-validated in 503 VA patients. Significant correlations between EEG discriminant scores, emergency admission measures, and post-trauma neuropsychological test scores validated the discriminant function as an index of severity of injury and a classifier of the extremes of severity. PMID- 11207334 TI - Depression does not influence basal ganglia-mediated psychomotor speed in HIV-1 infection. AB - The authors examined the effects of depressive mood (Hamilton Rating Scale for Depression [Ham-D]) on basal ganglia-mediated psychomotor speed (motor test battery) in 202 HIV-1 seropositive homosexual males with no prior history of antiretroviral treatment. HIV-1 seropositive patients showed a significant slowing of most rapid alternating movements (MRAM) and significantly prolonged contraction times (CT) compared with 66 HIV-1 seronegative male control subjects. Factor analysis of Ham-D scores isolated a factor containing the items depressed mood, suicide, and psychic and somatic anxiety. This factor did not correlate with MRAM or CT. Depression and psychomotor speed are independent in HIV 1infection. PMID- 11207335 TI - Ventricular enlargement in adults with profound mental retardation who demonstrate violent/destructive behaviors. AB - The authors determined brain ventricular size (ventricular brain ratio [VBR]) in 39 ambulatory adult mentally retarded individuals who did or did not require psychotropic medication for violent/destructive behavior. The mean VBR of mentally retarded patients who required psychotropic medication was significantly greater than the VBR of those who did not require such medication. PMID- 11207336 TI - Dissociative flashbacks after right frontal injury in a vietnam veteran with combat-related posttraumatic stress disorder. AB - A Vietnam veteran with a combat-related posttraumatic stress disorder developed recurrent dissociative flashbacks (related to the atrocities of a specific war incident) several months after suffering a traumatic brain injury. CT disclosed a small lesion in the right dorsolateral prefrontal cortex. SPECT demonstrated more extensive functional changes in prefrontal and anterior paralimbic brain regions, mainly in the right hemisphere. This case further implicates the provocative effect of physical stimuli (brain damage) in reawakening old dormant memories and the preferential role of the right hemisphere for the storage of traumatic memories. PMID- 11207337 TI - A "cure" for chronic combat-related posttraumatic stress disorder secondary to a right frontal lobe infarct: a case report. AB - A 48-year-old combat veteran sustained a right frontal cerebral infarct at the age of 45 years. The patient's family reports that prior to the infarct he had a preoccupation with memories of combat, as well as nightmares, avoidance of reminders, and multiple arousal symptoms. Since his recovery from the infarct, the patient and his family continue to relate significant arousal symptoms but deny any continued history of preoccupation with traumatic memories, reminder avoidance, or nightmares. The resolution of a limited number of symptoms in this patient following damage to the right frontal cortex suggests that some of the symptoms of posttraumatic stress disorder may be amenable to current biological interventions. PMID- 11207338 TI - Cerebellar-subcortical circuits and mania in cerebellar disease. PMID- 11207339 TI - Critical use of venlafaxine serology to uncover genetic rapid metabolism. PMID- 11207340 TI - Full remission of panic attacks in a schizophrenic patient after switching from haloperidol to risperidone. PMID- 11207341 TI - Risperidone addition and psychotic exacerbation. PMID- 11207342 TI - Obsessive-compulsive schizophrenia: a new diagnostic entity? PMID- 11207344 TI - A case of myasthenia gravis preceded by major depression. PMID- 11207349 TI - Gene-expression profiles in hereditary breast cancer. AB - BACKGROUND: Many cases of hereditary breast cancer are due to mutations in either the BRCA1 or the BRCA2 gene. The histopathological changes in these cancers are often characteristic of the mutant gene. We hypothesized that the genes expressed by these two types of tumors are also distinctive, perhaps allowing us to identify cases of hereditary breast cancer on the basis of gene-expression profiles. METHODS: RNA from samples of primary tumor from seven carriers of the BRCA1 mutation, seven carriers of the BRCA2 mutation, and seven patients with sporadic cases of breast cancer was compared with a microarray of 6512 complementary DNA clones of 5361 genes. Statistical analyses were used to identify a set of genes that could distinguish the BRCA1 genotype from the BRCA2 genotype. RESULTS: Permutation analysis of multivariate classification functions established that the gene-expression profiles of tumors with BRCA1 mutations, tumors with BRCA2 mutations, and sporadic tumors differed significantly from each other. An analysis of variance between the levels of gene expression and the genotype of the samples identified 176 genes that were differentially expressed in tumors with BRCA1 mutations and tumors with BRCA2 mutations. Given the known properties of some of the genes in this panel, our findings indicate that there are functional differences between breast tumors with BRCA1 mutations and those with BRCA2 mutations. CONCLUSIONS: Significantly different groups of genes are expressed by breast cancers with BRCA1 mutations and breast cancers with BRCA2 mutations. Our results suggest that a heritable mutation influences the gene expression profile of the cancer. PMID- 11207350 TI - Genetic variation in alcohol dehydrogenase and the beneficial effect of moderate alcohol consumption on myocardial infarction. AB - BACKGROUND: A polymorphism in the gene for alcohol dehydrogenase type 3 (ADH3) alters the rate of alcohol metabolism. We investigated the relation among the ADH3 polymorphism, the level of alcohol consumption, and the risk of myocardial infarction in a nested case-control study based on data from the prospective Physicians' Health Study. METHODS: We identified 396 patients with eligible newly diagnosed cases of myocardial infarction among men in the Physicians' Health Study. Of these patients, 374 were matched with 2 randomly selected control subjects each and the remaining 22 with 1 control each (total, 770 controls). The ADH3 genotype (gamma1gamma1, gamma1gamma2, or gamma2gamma2) was determined in all subjects. We examined the relations among the level of alcohol intake, the ADH3 genotype, and plasma high-density lipoprotein (HDL) levels in this study population and in a similar cohort of women. RESULTS: As compared with homozygosity for the allele associated with a fast rate of ethanol oxidation (gamma1), homozygosity for the allele associated with a slow rate of ethanol oxidation (gamma2) was associated with a reduced risk of myocardial infarction (relative risk, 0.65; 95 percent confidence interval, 0.43 to 0.99). Moderate alcohol consumption was associated with a decreased risk of myocardial infarction in all three genotype groups (gamma1gamma1, gamma1gamma2, and gamma2gamma2); however, the ADH3 genotype significantly modified this association (P=0.01 for the interaction). Among men who were homozygous for the gamma1 allele, those who consumed at least one drink per day had a relative risk of myocardial infarction of 0.62 (95 percent confidence interval, 0.34 to 1.13), as compared with the risk among men who consumed less than one drink per week. Men who consumed at least one drink per day and were homozygous for the gamma2 allele had the greatest reduction in risk (relative risk, 0.14; 95 percent confidence interval, 0.04 to 0.45). Such men also had the highest plasma HDL levels (P for interaction = 0.05). We confirmed the interaction among the ADH3 genotype, the level of alcohol consumption, and the HDL level in an independent study of postmenopausal women (P=0.02). CONCLUSIONS: Moderate drinkers who are homozygous for the slow oxidizing ADH3 allele have higher HDL levels and a substantially decreased risk of myocardial infarction. PMID- 11207351 TI - Lack of effect of induction of hypothermia after acute brain injury. AB - BACKGROUND: Induction of hypothermia in patients with brain injury was shown to improve outcomes in small clinical studies, but the results were not definitive. To study this issue, we conducted a multicenter trial comparing the effects of hypothermia with those of normothermia in patients with acute brain injury. METHODS: The study subjects were 392 patients 16 to 65 years of age with coma after sustaining closed head injuries who were randomly assigned to be treated with hypothermia (body temperature, 33 degrees C), which was initiated within 6 hours after injury and maintained for 48 hours by means of surface cooling, or normothermia. All patients otherwise received standard treatment. The primary outcome measure was functional status six months after the injury. RESULTS: The mean age of the patients and the type and severity of injury in the two treatment groups were similar. The mean (+/-SD) time from injury to randomization was 4.3+/ 1.1 hours in the hypothermia group and 4.1+/-1.2 hours in the normothermia group, and the mean time from injury to the achievement of the target temperature of 33 degrees C in the hypothermia group was 8.4+/-3.0 hours. The outcome was poor (defined as severe disability, a vegetative state, or death) in 57 percent of the patients in both groups. Mortality was 28 percent in the hypothermia group and 27 percent in the normothermia group (P=0.79). The patients in the hypothermia group had more hospital days with complications than the patients in the normothermia group. Fewer patients in the hypothermia group had high intracranial pressure than in the normothermia group. CONCLUSIONS: Treatment with hypothermia, with the body temperature reaching 33 degrees C within eight hours after injury, is not effective in improving outcomes in patients with severe brain injury. PMID- 11207352 TI - Intussusception among infants given an oral rotavirus vaccine. AB - BACKGROUND: Intussusception is a form of intestinal obstruction in which a segment of the bowel prolapses into a more distal segment. Our investigation began on May 27, 1999, after nine cases of infants who had intussusception after receiving the tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV) were reported to the Vaccine Adverse Event Reporting System. METHODS: In 19 states, we assessed the potential association between RRV-TV and intussusception among infants at least 1 but less than 12 months old. Infants hospitalized between November 1, 1998, and June 30, 1999, were identified by systematic reviews of medical and radiologic records. Each infant with intussusception was matched according to age with four healthy control infants who had been born at the same hospital as the infant with intussusception. Information on vaccinations was verified by the provider. RESULTS: Data were analyzed for 429 infants with intussusception and 1763 matched controls in a case-control analysis as well as for 432 infants with intussusception in a case-series analysis. Seventy-four of the 429 infants with intussusception (17.2 percent) and 226 of the 1763 controls (12.8 percent) had received RRV-TV (P=0.02). An increased risk of intussusception 3 to 14 days after the first dose of RRV-TV was found in the case-control analysis (adjusted odds ratio, 21.7; 95 percent confidence interval, 9.6 to 48.9). In the case-series analysis, the incidence-rate ratio was 29.4 (95 percent confidence interval, 16.1 to 53.6) for days 3 through 14 after a first dose. There was also an increase in the risk of intussusception after the second dose of the vaccine, but it was smaller than the increase in risk after the first dose. Assuming full implementation of a national program of vaccination with RRV TV, we estimated that 1 case of intussusception attributable to the vaccine would occur for every 4670 to 9474 infants vaccinated. CONCLUSIONS: The strong association between vaccination with RRV-TV and intussusception among otherwise healthy infants supports the existence of a causal relation. Rotavirus vaccines with an improved safety profile are urgently needed. PMID- 11207353 TI - A mutation in the surfactant protein C gene associated with familial interstitial lung disease. PMID- 11207354 TI - Images in clinical medicine. Four types of acute post-traumatic intracranial hemorrhage. PMID- 11207355 TI - Neonatal hyperbilirubinemia. PMID- 11207356 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 6-2001. A 17-year-old girl with marked jaundice and weight loss. PMID- 11207357 TI - Genome-wide views of cancer. PMID- 11207358 TI - Hypothermia for traumatic brain injury--a good idea proved ineffective. PMID- 11207359 TI - Quality control of mRNA function. PMID- 11207360 TI - A general model for nucleic acid helicases and their "coupling" within macromolecular machines. PMID- 11207361 TI - Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, cartilage-hair hypoplasia. AB - The recessively inherited developmental disorder, cartilage-hair hypoplasia (CHH) is highly pleiotropic with manifestations including short stature, defective cellular immunity, and predisposition to several cancers. The endoribonuclease RNase MRP consists of an RNA molecule bound to several proteins. It has at least two functions, namely, cleavage of RNA in mitochondrial DNA synthesis and nucleolar cleaving of pre-rRNA. We describe numerous mutations in the untranslated RMRP gene that cosegregate with the CHH phenotype. Insertion mutations immediately upstream of the coding sequence silence transcription while mutations in the transcribed region do not. The association of protein subunits with RNA appears unaltered. We conclude that mutations in RMRP cause CHH by disrupting a function of RNase MRP RNA that affects multiple organ systems. PMID- 11207362 TI - Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. AB - Chloride channels play important roles in the plasma membrane and in intracellular organelles. Mice deficient for the ubiquitously expressed ClC-7 Cl( ) channel show severe osteopetrosis and retinal degeneration. Although osteoclasts are present in normal numbers, they fail to resorb bone because they cannot acidify the extracellular resorption lacuna. ClC-7 resides in late endosomal and lysosomal compartments. In osteoclasts, it is highly expressed in the ruffled membrane, formed by the fusion of H(+)-ATPase-containing vesicles, that secretes protons into the lacuna. We also identified CLCN7 mutations in a patient with human infantile malignant osteopetrosis. We conclude that ClC-7 provides the chloride conductance required for an efficient proton pumping by the H(+)-ATPase of the osteoclast ruffled membrane. PMID- 11207363 TI - MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis. AB - The subthreshold, voltage-gated potassium channel of skeletal muscle is shown to contain MinK-related peptide 2 (MiRP2) and the pore-forming subunit Kv3.4. MiRP2 Kv3.4 channels differ from Kv3.4 channels in unitary conductance, voltage dependent activation, recovery from inactivation, steady-state open probability, and block by a peptide toxin. Thus, MiRP2-Kv3.4 channels set resting membrane potential (RMP) and do not produce afterhyperpolarization or cumulative inactivation to limit action potential frequency. A missense mutation is identified in the gene for MiRP2 (KCNE3) in two families with periodic paralysis and found to segregate with the disease. Mutant MiRP2-Kv3.4 complexes exhibit reduced current density and diminished capacity to set RMP. Thus, MiRP2 operates with a classical potassium channel subunit to govern skeletal muscle function and pathophysiology. PMID- 11207364 TI - Morphogenesis and renewal of hair follicles from adult multipotent stem cells. AB - The upper region of the outer root sheath of vibrissal follicles of adult mice contains multipotent stem cells that respond to morphogenetic signals to generate multiple hair follicles, sebaceous glands, and epidermis, i.e., all the lineages of the hairy skin. At the time when hair production ceases and when the lower region of the follicle undergoes major structural changes, the lower region contains a significant number of clonogenic keratinocytes, and can then respond to morphogenetic signals. This demonstrates that multipotent stem cells migrate to the root of the follicle to produce whisker growth. Moreover, our results indicate that the clonogenic keratinocytes are closely related, if not identical, to the multipotent stem cells, and that the regulation of whisker growth necessitates a precise control of stem cell trafficking. PMID- 11207365 TI - A human BRCA2 complex containing a structural DNA binding component influences cell cycle progression. AB - Germline mutations of the human BRCA2 gene confer susceptibility to breast cancer. Although the function of the BRCA2 protein remains to be determined, murine cells homozygous for BRCA2 inactivation display chromosomal aberrations. We have isolated a 2 MDa BRCA2-containing complex and identified a structural DNA binding component, designated as BRCA2-Associated Factor 35 (BRAF35). BRAF35 contains a nonspecific DNA binding HMG domain and a kinesin-like coiled coil domain. Similar to BRCA2, BRAF35 mRNA expression levels in mouse embryos are highest in proliferating tissues with high mitotic index. Strikingly, nuclear staining revealed a close association of BRAF35/BRCA2 complex with condensed chromatin coincident with histone H3 phosphorylation. Importantly, antibody microinjection experiments suggest a role for BRCA2/BRAF35 complex in modulation of cell cycle progression. PMID- 11207366 TI - Branch migration and Holliday junction resolution catalyzed by activities from mammalian cells. AB - During homologous recombination, DNA strand exchange leads to Holliday junction formation. The movement, or branch migration, of this junction along DNA extends the length of the heteroduplex joint. In prokaryotes, branch migration and Holliday junction resolution are catalyzed by the RuvA and RuvB proteins, which form a complex with RuvC resolvase to form a "resolvasome". Mammalian cell-free extracts have now been fractionated to reveal analogous activities. An ATP dependent branch migration activity, which migrates junctions through >2700 bp, cofractionates with the Holliday junction resolvase during several chromatographic steps. Together, the two activities promote concerted branch migration/resolution reactions similar to those catalyzed by E. coli RuvABC, highlighting the preservation of this essential pathway in recombination and DNA repair from prokaryotes to mammals. PMID- 11207367 TI - Replication initiation proteins regulate a developmental checkpoint in Bacillus subtilis. AB - We identified a signaling pathway that prevents initiation of sporulation in Bacillus subtilis when replication initiation is impaired. We isolated mutations that allow a replication initiation mutant (dnaA) to sporulate. These mutations affect a small open reading frame, sda, that was overexpressed in replication initiation mutants and appears to be directly regulated by DnaA. Mutations in replication initiation genes inhibit the onset of sporulation by preventing activation of a transcription factor required for sporulation, Spo0A. Deletion of sda restored activation of Spo0A in replication initiation mutants. Overexpression of sda in otherwise wild-type cells inhibited activation of Spo0A and sporulation. Purified Sda inhibited a histidine kinase needed for activation of Spo0A. Our results indicate that control of sda by DnaA establishes a checkpoint that inhibits activation of Spo0A and prevents futile attempts to initiate sporulation. PMID- 11207368 TI - Lipoxygenase mRNA silencing in erythroid differentiation: The 3'UTR regulatory complex controls 60S ribosomal subunit joining. AB - 15-lipoxygenase (LOX) expression is translationally silenced in early erythroid precursor cells by a specific mRNA-protein complex formed between the differentiation control element in the 3' untranslated region (UTR) and hnRNPs K and E1. The 3'UTR regulatory complex prevents translation initiation by an unknown mechanism. We demonstrate that the 40S ribosomal subunit can be recruited and scan to the translation initiation codon even when the silencing complex is bound to the 3'UTR. However, the joining of the 60S ribosomal subunit at the AUG codon to form a translation competent 80S ribosome is inhibited, unless initiation is mediated by the IGR-IRES of the cricket paralysis virus. These findings identify the critical step at which LOX mRNA translation is controlled and reveal that 60S subunit joining can be specifically regulated. PMID- 11207369 TI - Structure of the complete extracellular domain of the common beta subunit of the human GM-CSF, IL-3, and IL-5 receptors reveals a novel dimer configuration. AB - The receptor systems for the hemopoietic cytokines GM-CSF, IL-3, and IL-5 consist of ligand-specific alpha receptor subunits that play an essential role in the activation of the shared betac subunit, the major signaling entity. Here, we report the structure of the complete betac extracellular domain. It has a structure unlike any class I cytokine receptor described thus far, forming a stable interlocking dimer in the absence of ligand in which the G strand of domain 1 hydrogen bonds into the corresponding beta sheet of domain 3 of the dimer-related molecule. The G strand of domain 3 similarly partners with the dimer-related domain 1. The structure provides new insights into receptor activation by the respective alpha receptor:ligand complexes. PMID- 11207370 TI - Crystal structure of a complement control protein that regulates both pathways of complement activation and binds heparan sulfate proteoglycans. AB - Vaccinia virus complement control protein (VCP) inhibits both pathways of complement activation through binding the third and fourth components. A homolog of mammalian regulators of complement activation, its ability to bind heparin endows VCP with additional activities of significance to viral infectivity. The structure of VCP reveals a highly extended molecule with a putative heparin recognition site at its C-terminal end. A second cluster of positive charges provides a possibly overlapping binding site for both heparin and complement components. Experiments suggested by the structure indicate that VCP can bind heparin and control complement simultaneously. This, the structure of any intact regulator of complement activation, along with attendant functional insights, will stimulate the design of new therapeutic inhibitors of complement. PMID- 11207371 TI - Protein sorting upon exit from the endoplasmic reticulum. AB - It is currently thought that all secretory proteins travel together to the Golgi apparatus where they are sorted to different destinations. However, the specific requirements for transport of GPI-anchored proteins from the endoplasmic reticulum to the Golgi apparatus in yeast could be explained if protein sorting occurs earlier in the pathway. Using an in vitro assay that reconstitutes a single round of budding from the endoplasmic reticulum, we found that GPI anchored proteins and other secretory proteins exit the endoplasmic reticulum in distinct vesicles. Therefore, GPI-anchored proteins are sorted from other proteins, in particular other plasma membrane proteins, at an early stage of the secretory pathway. These results have wide implications for the mechanism of protein exit from the endoplasmic reticulum. PMID- 11207374 TI - The roles of iron in health and disease. AB - Iron is vital for almost all living organisms by participating in a wide variety of metabolic processes, including oxygen transport, DNA synthesis, and electron transport. However, iron concentrations in body tissues must be tightly regulated because excessive iron leads to tissue damage, as a result of formation of free radicals. Disorders of iron metabolism are among the most common diseases of humans and encompass a broad spectrum of diseases with diverse clinical manifestations, ranging from anemia to iron overload and, possibly, to neurodegenerative diseases. The molecular understanding of iron regulation in the body is critical in identifying the underlying causes for each disease and in providing proper diagnosis and treatments. Recent advances in genetics, molecular biology and biochemistry of iron metabolism have assisted in elucidating the molecular mechanisms of iron homeostasis. The coordinate control of iron uptake and storage is tightly regulated by the feedback system of iron responsive element-containing gene products and iron regulatory proteins that modulate the expression levels of the genes involved in iron metabolism. Recent identification and characterization of the hemochromatosis protein HFE, the iron importer Nramp2, the iron exporter ferroportin1, and the second transferrin-binding and transport protein transferrin receptor 2, have demonstrated their important roles in maintaining body's iron homeostasis. Functional studies of these gene products have expanded our knowledge at the molecular level about the pathways of iron metabolism and have provided valuable insight into the defects of iron metabolism disorders. In addition, a variety of animal models have implemented the identification of many genetic defects that lead to abnormal iron homeostasis and have provided crucial clinical information about the pathophysiology of iron disorders. In this review, we discuss the latest progress in studies of iron metabolism and our current understanding of the molecular mechanisms of iron absorption, transport, utilization, and storage. Finally, we will discuss the clinical presentations of iron metabolism disorders, including secondary iron disorders that are either associated with or the result of abnormal iron accumulation. PMID- 11207375 TI - Effects of chronic alcohol ingestion on the mesostriatal dopamine system in the rat. AB - The effects of chronic alcohol use on the mesostriatal dopamine (DA) system remain relatively unknown. The aim of the present study was to assess multiple measures of the status of the mesostriatal DA system in rats chronically fed an alcohol diet for approximately 1 year. Tissue levels of DA and its metabolite, 3,4-dihydroxyphenylacetic acid, were significantly decreased in both the dorsal striatum (34 and 33%, respectively) and ventral striatum (33 and 36%, respectively) in alcohol-fed rats compared to pair-fed matched controls. Western blotting revealed a mean 20% decrease in tyrosine hydroxylase protein levels in the dorsal and ventral striatum of alcohol-fed animals while dopamine transporter protein levels from the same animals were significantly increased compared to controls (mean 60% increase for the dorsal and ventral striatum). The present results demonstrate significant alterations in the mesostriatal DA system after 1 year of chronic alcohol use. It is possible that the observed changes in DA synthesis and re-uptake measures result in altered intracellular and extracellular DA levels, perhaps contributing to the addictive properties of alcohol. PMID- 11207376 TI - Beta-amyloid peptide induces the expression of voltage dependent outward rectifying K+ channels in rat microglia. AB - Upregulation of voltage-dependent outward rectifying K+ (Kv) channels has been reported in activated microglia. Since beta-amyloid peptide (A beta) is known to activate microglia, we tested whether the exposure of cultured rat microglia to A beta fragment 25-35 (A beta 25-35) induced the Kv current. A beta 25-35 in 5-200 nM concentration range significantly increased Kv current density, while there was small change in inward rectifying K+ current density. The full length A beta peptide (A beta 1-42) also increased Kv current. However, the control peptide, A beta 35-25, did not induce Kv current. Most of the Kv current induced by A beta was specifically blocked by the presence of antisense deoxyoligonucleotides against Kv1.3, and Kv1.5. Thus, it is concluded that we have identified Kv1.3 and Kv1.5 as the channel types expressed in A beta-treated microglia. PMID- 11207377 TI - Calcitonin gene-related peptide modifies the ectopic discharge from damaged nerve fibres in the ferret. AB - Previous studies in our laboratory have shown that the neuropeptide, calcitonin gene-related peptide (CGRP) accumulates at a site of inferior alveolar nerve injury at the time when high levels of spontaneous activity and mechanical sensitivity are recorded electrophysiologically. The present study was undertaken to determine whether or not the CGRP could be playing a role in initiating or modulating the neuronal activity. In 18 anaesthetised adult ferrets the left inferior alveolar nerve was sectioned and ligated and recovery permitted for 3 days. Under a second anaesthetic recordings were made from a fine nerve filament, containing up to four active or silent units, dissected from the nerve proximal to the injury. After recording activity for a 30 min control period, CGRP and then the CGRP antagonist (CGRP 8-37) were applied either by close-arterial injection or topically (10(-4) M, 0.2 ml). After each application activity was recorded for a 30 min period. Recordings were made from 52 units, of which 26 (50%) were spontaneously active and 30 (58%) were mechanically sensitive. The spontaneous activity in five units was increased by the application of CGRP, and the CGRP antagonist subsequently reduced the activity in two of these units. Activity was induced by CGRP in three previously silent units. Overall, activity was affected in 19% of the units studied. We conclude that CGRP present within a neuroma may initiate or modulate the level of ectopic discharge from some damaged nerve fibres and therefore may contribute to the sensory disturbances which follow nerve injury. PMID- 11207378 TI - Induction of polysialic acid-neural cell adhesion molecule in surviving motoneurons of transgenic amyotrophic lateral sclerosis mice. AB - The highly polysialylated neural cell adhesion molecule (PSA-NCAM) is recognized as a marker of neurogenesis or neural plasticity in adult nervous system. PSA NCAM expression was examined in the spinal cord of transgenic mice harboring a mutant Cu/Zn superoxide dismutase (SOD1) gene. Immunohistochemistry showed a progressive expression of PSA-NCAM in surviving motoneurons of spinal ventral horns from an early and presymptomatic stage (25 weeks) before significant loss of ventral horn neurons, while no detectable PSA-NCAM in the ventral horn of non transgenic littermates during the ageing process. The present data suggest that a specific expression of PSA-NCAM may be involved in the survival of spinal motoneurons under pathological conditions such as amyotrophic lateral sclerosis. PMID- 11207379 TI - Intrapallidal D2 dopamine receptors control globus pallidus neuron activity in the rat. AB - Because activation of D2 dopamine receptors inhibits gamma-aminobutyric acid (GABA) release from intrapallidal nerve terminals, we measured the effects of modifiers of dopamine D2 receptors on the firing rate of single neurons in the globus pallidus (GP) of the anesthetized rat. The predominant effect of intrapallidal administration of the selective D2 agonist quinpirole was an increase in the rate of spontaneous firing while the D2 blocker sulpiride caused a decrease. The spontaneous firing of GP neurons is inhibited by stimulation of the GABAergic striatopallidal projection. We therefore measured the effects of modifiers of D2 receptors on striatal inhibition of GP neurons and found that intrapallidal quinpirole blocked the inhibitory effects of striatal stimulation while sulpiride enhanced them. These experiments show that both the spontaneous rate of firing of pallidal neurons and its modification by striatopallidal inputs is controlled by intrapallidal dopamine D2 receptors. In addition, taken together with other findings in the literature, our results suggest that activation of dopamine D2 receptors within the globus pallidus leads to inhibition of GABA release from presynaptic terminals. PMID- 11207380 TI - Transient receptor potential protein mRNA expression in rat substantia nigra. AB - Receptor gated Ca2+ entry has been associated with transient receptor potential (TRP) proteins encoded by several different genes. Here, we compare expression of mRNA for TRP isoforms encoded by genes TRP1-6 in the rat substantia nigra and whole brain. The substantia nigra and the whole brain expressed mRNA predominantly for TRP3 and TRP6. The levels of TRP1, 2, 4 and 5 were very low in both. The TRP6 mRNA levels in substantia nigra and the whole brain were comparable while those for TRP3 were significantly lower in substantia nigra than in the whole brain. Thus substantia nigra differs from the whole brain in its TRP expression. PMID- 11207381 TI - Hyperpolarizing shift by quinine in the steady-state inactivation curve of delayed rectifier-type potassium current in bullfrog sympathetic neurons. AB - Whole-cell recordings were made from dissociated bullfrog sympathetic neurons to examine the actions of quinine (1-100 microM) on the steady-state activation and inactivation curves of a delayed rectifier-type potassium current (I(K)). Quinine (EC50 approximately 8 microM) caused a hyperpolarizing shift (approximately 31 mV with 30 microM) in the inactivation curve of I(K) without significantly affecting its activation curve. Quinine (20 microM) was without effects on the voltage dependence of a rapidly-inactivating A-type potassium current (I(A)). It is concluded that quinine can selectively modulate the voltage-dependence of I(K) in amphibian autonomic neurons. PMID- 11207383 TI - Tau protein in cerebrospinal fluid (CSF): a blood-CSF barrier related evaluation in patients with various neurological diseases. AB - Tau protein (tau) is primarily localised in neurons, and after brain parenchymal damage its release into cerebrospinal fluid (CSF) is increased. The particular influences of blood-CSF barrier function and of disease topography on CSF tau levels have not been studied yet. CSF tau concentrations determined by enzyme immunoassay in various neurological diseases (n = 61) were not dependent upon blood-CSF barrier dysfunction. Significant elevation of tau levels in patients with meningoencephalitis and cerebral hemorrhage indicates brain parenchymal damage. In contrast, tau levels remained normal in patients with bacterial meningitis if encephalitic complications did not occur. In patients with Guillain Barre syndrome tau levels were low. Increased tau levels in active multiple sclerosis compared to clinically nonactive states indicate axonal pathology in active disease. PMID- 11207382 TI - Functional expression of cholecystokinin-A receptor on ventromedial hypothalamic neurons in the immature rat brain. AB - Cholecystokinin-8 (CCK-8) dose-dependently increased the cytosolic Ca2+ concentration ([Ca]i) in ventromedial hypothalamic neurons acutely dissociated from the immature rat brain. The CCK-8 response was mimicked by caerulein, but not by CCK(B) agonists, and was often inhibited by CCK(A) receptor antagonists, but rarely by CCK(B) receptor antagonists. The response was dependent on external Ca2+ and Na+, and was inhibited by voltage-dependent Ca2+ channel blockers. The results suggest that CCK-8-induced depolarization via CCK(A) receptors increased Ca2+ influx through a voltage-dependent Ca2+ channel, which in turn increased [Ca]i. PMID- 11207384 TI - A monoclonal antibody that enables specific immunohistological detection of prion protein in bovine spongiform encephalopathy cases. AB - The specificity of a monoclonal antibody (mAB) raised against recombinant bovine prion protein (PrP) for the immunohistological detection of PrP accumulation in the medulla oblongata of bovine spongiform encephalopathy (BSE) and ovine scrapie cases was investigated. mAB KG9 showed a diffuse low intensity reaction with the cytoplasm of neurones in normal cattle and sheep sections. In BSE sections the mAB detected widespread granular deposits of PrP associated with neurones and the neuropil. Although scrapie sections showed similar levels of granular deposits with another antibody to PrP these were not detected by KG9 which did however detect diffuse staining in neuronal cytoplasm. Possible explanations for the specificity of binding of KG9 are discussed. PMID- 11207385 TI - Caspase activation as an apoptotic evidence in the gerbil hippocampal CA1 pyramidal cells following transient forebrain ischemia. AB - To determine whether apoptotic process is involved in the delayed neuronal death in hippocampal CA1 region following forebrain ischemia in gerbils, time dependent activation of caspase and DNA fragmentation were evaluated by immuno-staining and terminal dUTP nick-end-labeling staining, respectively. After transient forebrain ischemia in gerbils, activation of apoptosis related caspase, including caspase 3, was apparent, and it preceded DNA fragmentation in CA1 region. These observations suggest that apoptotic process is involved in hippocampal delayed neuronal death. PMID- 11207386 TI - The role of the chorda tympani nerve in the activation of the rat hypothalamic histaminergic system by leptin. AB - A possible pathway through which leptin activates the histaminergic system was studied using in vivo microdialysis in rats. Intraperitoneal injection of leptin (1.3 mg/kg) caused a significant increase in hypothalamic histamine release, however, its intracerebroventricular injection (10 microg/rat) did not cause any significant changes in the release. Furthermore, leptin (1.3 mg/kg) had no effect on histamine release in rats whose chorda tympani nerves, a branch of the facial nerve which mediates taste information, were transected bilaterally. These findings indicate that leptin activates the histaminergic system by the peripheral signal inputs via the chorda tympani resulting in the suppression of food intake. PMID- 11207388 TI - Collaboration of fibronectin matrix and neurotrophin in regulating spontaneous transmitter release at developing neuromuscular synapses in Xenopus cell cultures. AB - Integrins mediate cell-extracellular matrix connection and are particularly important during neuronal development. We here investigated the regulation of fibronectin (FN) matrix and neurotrophins on the embryonic synaptic transmission. Spontaneous synaptic currents (SSCs) were recorded from innervated myocytes of 1 day-old Xenopus cultures by whole-cell recordings. The SSC increasing action of alpha,beta-methylene adenosine triphosphate was enhanced in neurons grown on FN substratum, which was further potentiated by chronic treatment with brain-derived neurotrophic factor (BDNF). The SSC increasing action of thapsigargin, carbonyl cyanide m-chlorophenylhydrazone and N-methyl-D-aspartate was also markedly potentiated in neurons grown on FN-coated glass coverslips and chronically treated with BDNF. FN matrix or BDNF alone only exerts slight potentiation on the SSC increasing action of these three drugs. Our results suggest that FN matrix can collaborate with neurotrophin in regulating synaptic transmission at developing motoneurons, which may play an important role in the maturation of embryonic neuromuscular junction. PMID- 11207387 TI - Cloning of mouse BMAL2 and its daily expression profile in the suprachiasmatic nucleus: a remarkable acceleration of Bmal2 sequence divergence after Bmal gene duplication. AB - Brain-Muscle-Arnt-Like-protein 2 (BMAL2; Arnt4) (aryl hydrocarbon receptor nuclear translocator) is a recently identified basic Helix-Loop-Helix-Per-Arnt Sim (bHLH-PAS) transcription factor, which contributes to a positive regulation of autoregulatory feedback loop in vertebrate circadian clock systems. In this study, we cloned cDNAs encoding mouse and rat BMAL2 (mBMAL2 and rBMAL2) from mouse midbrain and rat-1 fibroblast cells, respectively. A phylogenetic analysis strongly suggested that vertebrate Bmal1 and Bmal2 genes were generated by a single gene duplication of an ancestral Bmal gene, a vertebrate ortholog of dCyc gene, and that 'BMAL2's putatively termed so far are orthologous. Interestingly, BMAL2 proteins have diverged about 20-fold more rapidly than BMAL1 proteins after the duplication, suggesting an as-yet-unidentified function conserved in BMAL1 but not in BMAL2. mBmal2 mRNA was constitutively expressed throughout the day under light-dark cycle in the mouse hypothalamus containing suprachiasmatic nucleus, the site of the central circadian oscillator in mammals. PMID- 11207389 TI - Expression of dystrophin in the mouse myenteric neurones. AB - Dystrophin, a membrane-associated protein, plays relevant roles in cell functions. Its lack or trunkated expression results in Duchenne muscular dystrophy (DMD), a pathology associated with alterations in gastrointestinal motility considered to be neural in origin. No data are available on the presence of dystrophin in myenteric neurones. We labelled mouse myenteric neurones with DYS1-, DYS2-, DYS3-antibodies; staining was located on the perikarya and processes, with no differences in distribution or intensity among the antibodies; the western immunoblot analysis indicated that myenteric neurones express several dystrophin isoforms; anti-dystrophins/anti-neuronal specific enolase double labeling confirmed that all neurones express dystrophin. Dystrophin in myenteric neurones might play a role in cytoskeletal organization, axonal transport and signal pathways; its lack might cause the intestinal motor abnormalities reported in DMD patients. PMID- 11207390 TI - Genetic studies in Parkinson's disease with an alpha-synuclein/NACP gene polymorphism in Japan. AB - Dinucleotide repeat polymorphism has been observed in the promoter of the alpha synuclein (alpha-SYN)/NAC precursor protein (NACP) gene. Alpha-SYN/NACP allele 3 (described by Xia et al. (Ann. Neurol., 40 (1996) 207), equivalent to allele 1 described by Kruger et al. (Ann. Neurol. 45 (1999) 611) is reported to be significantly more frequent among patients with sporadic Parkinson's disease (sPD) than controls. In this study, we genotyped the same alpha-SYN/NACP polymorphism in Japanese sPD patients and healthy controls, but found that any aliele showed no significant difference between the two groups. PMID- 11207391 TI - Assessing placebo effects without placebo groups: an untapped possibility? PMID- 11207392 TI - Response variability to analgesics: a role for non-specific activation of endogenous opioids. AB - Individual differences in pharmacokinetics and pharmacodynamics, the type of pain and the method of drug administration can account for the response variability to analgesics. By integrating a clinical and an experimental approach, we report here that another important source of variability is represented by individual differences in non-specific (placebo) activation of endogenous opioid systems. In the first part of this study, we analyzed the effectiveness of buprenorphine, tramadol, ketorolac and metamizol in the clinical setting, where the placebo effect was completely eliminated by means of hidden infusions. We found that the hidden injections were significantly less effective and less variable compared with open injections (in full view of the subject), suggesting that part of the response variability was due to non-specific factors (placebo). Since we could not administer the opioid antagonist, naloxone, to these patients, in the second part of this study, we induced experimental ischemic arm pain in healthy volunteers and found that, as occurred in clinical pain, the analgesic response to a hidden injection of the non-opioid ketorolac was less effective and less variable than an open injection. Most importantly, we obtained the same effects by adding naloxone to an open injection of ketorolac, thus blocking the opioid mediated placebo component of analgesia. These findings indicate that both the psychological (hidden injection) and pharmacological (naloxone) blockade of the placebo response reduce the effectiveness of, and the response variability to, analgesic drugs. Therefore, an important source of response variability to analgesics appears to be due to differences in non-specific activation of endogenous opioid systems. PMID- 11207393 TI - The effects of GABA(B) agonists and gabapentin on mechanical hyperalgesia in models of neuropathic and inflammatory pain in the rat. AB - We have examined the effects of a novel GABA(B) agonist, CGP35024, in models of chronic neuropathic (partial sciatic ligation) and inflammatory (Freund's complete adjuvant) pain in the rat, and its inhibitory action on spinal transmission in vitro. The effects of CGP35024 were compared with L-baclofen and gabapentin. CGP35024 and L-baclofen reversed neuropathic mechanical hyperalgesia following single subcutaneous or intrathecal administration, but did not affect inflammatory mechanical hyperalgesia. Gabapentin only moderately affected neuropathic hyperalgesia following a single administration by either route, but produced significant reversal following daily administration for 5 days. It was only weakly active against inflammatory hyperalgesia following single or repeated administration. The antihyperalgesic effects of L-baclofen and CGP35024, but not gabapentin, were blocked by the selective GABA(B) receptor antagonist CGP56433A. CGP35024 was seven times more potent against neuropathic hyperalgesia than in the rotarod test for motor co-ordination, whilst L-baclofen was approximately equipotent in the two tests. In the isolated hemisected spinal cord from the rat, CGP35024, L-baclofen and gabapentin all inhibited capsaicin-evoked ventral root potentials (VRPs). CGP35024 and L-baclofen, but not gabapentin, also inhibited the polysynaptic and monosynaptic phases of electrically-evoked VRPs, as well as the 'wind-up' response to repetitive stimulation. These data indicate that CGP35024 and L-baclofen modulate nociceptive transmission in the spinal cord to inhibit neuropathic hyperalgesia, and that CGP35024 has a therapeutic window for antihyperalgesia over spasmolysis. PMID- 11207394 TI - Modulation of neuronal activity in the nucleus raphe magnus by the 5-HT(1) receptor agonist naratriptan in rat. AB - Modulatory effects of the new antimigraine drug naratriptan, a 5-HT(1)-receptor agonist, on neurons of the nucleus raphe magnus were examined in rat by extracellular recordings. In the nucleus raphe magnus neuronal activity decreased in on-cells and increased in off-cells after intravenous administration of naratriptan. The modulatory effects of naratriptan were similar to the well-known effects of morphine on neurons in the nucleus raphe magnus. The results of this study suggest central actions of naratriptan and may point to an involvement of the endogenous pain control system in the antinociceptive effects of the 5-HT(1) receptor-agonist. PMID- 11207395 TI - Somatostatin receptors on peripheral primary afferent terminals: inhibition of sensitized nociceptors. AB - Somatostatin (SST) is in primary afferent neurons and reduces vascular and nociceptive components of inflammation. SST receptor (SSTR) agonists provide analgesia following intrathecal or epidural administration in humans, but neurotoxicity in the central nervous system (CNS) has been reported in experimental animals. With the rationale that targeting peripheral SSTRs would provide effective analgesia while avoiding CNS side effects, the goals of the present study are to investigate the presence of SSTRs on peripheral primary afferent fibers and determine the behavioral and physiological effects of the SST agonist octreotide (OCT) on formalin-induced nociception and bradykinin-induced primary afferent excitation and sensitization in the rat. The results demonstrate that: (1) SSTR2as are present on 11% of peripheral primary afferent sensory fibers in rat glabrous skin; (2) intraplantar injection of OCT reduces formalin induced nociceptive behaviors; (3) OCT reduces, in a dose-dependent fashion, responses to thermal stimulation in C-mechanoheat sensitive fibers; and (4) OCT reduces the responses of C-mechanoheat fibers to bradykinin-induced excitation and sensitization to heat. Each of these actions can be reversed following co injection of OCT with the SSTR antagonist cyclo-somatostatin (c-SOM). Thus, activation of peripheral SSTRs reduces both inflammatory pain and the activity of sensitized nociceptors, avoids deleterious CNS side effects and may be clinically useful in the treatment of pain of peripheral origin. PMID- 11207396 TI - Orofacial pain symptoms: an interaction between age and sex. AB - This study investigated sex and age cohort differences in the subjective report of orofacial pain symptoms in a stratified sample of community dwelling adults. The subjects were 724 participants in the Florida Dental Care Study, a longitudinal study of oral health among dentate adults, age 45 and older at baseline. Pain prevalence and subjective ratings were assessed for a range of orofacial pain sites using a standardized telephone interview. The results suggest that the 6-month prevalence of jaw joint pain (8.3%), face pain (3.1%), toothache pain (12.0%), painful oral sores (15.6%), and burning mouth (1.6%) found in the FDCS sample are similar to United States population estimates. In addition, prevalence for pain when chewing and temperature sensitivity were also reported as 23% and 24% respectively, suggesting that these two seldom documented painful experiences are common. Female respondents reported higher 6-month prevalence for multiple symptoms and painful oral sores, with trends also observed for female sex as a risk factor for jaw joint pain and face pain, whereas males were more likely to report temperature sensitivity. A higher percentage of females rated their pain as severe enough to impact behavior for jaw joint pain, toothache pain, and painful oral sores. Few overall age effects were found, with the exception of higher prevalence of temperature sensitivity and pain when chewing in the 45--64-year-old group, compared to respondents in the 65+ age cohort. However, the most interesting finding was that when sex by age cohort comparisons were made, with the exception of painful oral sores, all significant differences in pain ratings were found within the 45--64-year-old cohort and not the 65+ group. This finding clarified inconsistencies found in earlier studies in the orofacial pain literature where sex differences in pain ratings were found in several adult samples of a wide range of ages but not in a sample of older adults. PMID- 11207397 TI - Role of the dopaminergic system in chronic pain -- a fluorodopa-PET study. AB - Recent data from animal experiments suggest an important role for the basal ganglia in the processing and sensorimotor gating of nociceptive information. However, very little is known about their possible participation in human pain. Because of our previous finding of increased excitability of the blink reflex (a brainstem reflex under dopaminergic inhibitory control) in some burning mouth syndrome (BMS) patients, we have studied the dopaminergic function of the striatum (putamen and caudatus) of BMS patients with positron emission tomography (PET). 6-[(18)F]fluorodopa (FDOPA) PET scans were done on ten BMS patients and 14 healthy control subjects. The presynaptic dopaminergic function was significantly decreased in the right putamen (20%, P=0.04) of the BMS patients compared to control subjects. On the left side, the FDOPA uptake was decreased by 17% (P=0.08). The mean FDOPA uptake was not significantly changed in the caudate nucleus of the patients. The finding of decreased striatal FDOPA uptake in the putamen supports our previous neurophysiological observations indicating decreased dopaminergic inhibition in BMS patients. The present result provides direct evidence of the involvement of the nigrostriatal dopaminergic system in pain for the first time in a clinical pain condition. PMID- 11207398 TI - Characteristics and prediction of early pain after laparoscopic cholecystectomy. AB - Small-scale studies have suggested a large inter-individual variation in early postoperative pain after laparoscopic cholecystectomy, emphasizing the need for improved analgesic treatment and valid predictors. We investigated prospectively the association between a preoperative nociceptive stimulus by ice water (cold pressor test), neuroticism, dyspepsia, patient history of biliary symptoms, intraoperative factors, and demographic information in 150 consecutive patients undergoing uncomplicated laparoscopic cholecystectomy for their influence on early postoperative pain. During the first postoperative week patients registered overall pain, incisional, visceral, and shoulder pain on a visual analogue scale and verbal rating scale, and daily analgesic requirements were noted. Throughout the first postoperative week overall pain showed a pronounced inter-individual variability. Incisional pain dominated in incidence and intensity compared with visceral pain, which in turn dominated over shoulder pain. In a multivariate analysis model, preoperative neuroticism, sensitivity to cold pressor-induced pain, and age were identified as independent risk factors for early postoperative pain. Our results suggest that future analgesic studies after laparoscopic cholecystectomy should focus on reduction of incisional pain. PMID- 11207400 TI - Oral mucosal blood flow in patients with burning mouth syndrome. AB - The pathophysiology of burning mouth syndrome (BMS) is largely unknown. Thus, the aim was to study oral mucosal blood flow in BMS-patients using laser Doppler flowmetry (LDF). Thirteen BMS patients (11 female, two male; mean age+/-SD 64.3+/ 7.9 years, mean disease duration 18.9+/-6.2 months) and 13 healthy non-smoking controls matched for age and gender (11 female, two male; mean age 64.7+/-8.1 years) were investigated. Using the LDF technique mucosal blood flow (mBF) was measured at the hard palate, the tip of the tongue, on the midline of the oral vestibule, and on the lip. Measurements were made at rest and over 2 min following dry ice application of 10 s duration using a pencil shaped apparatus. In addition, blood pressure (BP), heart rate (HR), peripheral cutaneous blood flow, and transcutaneous pCO(2) were continuously recorded. Mucosal blood flow (mBF) increased at all measurement sites in response to dry ice application (P<0.001) with peak flow at 0.5--1.5 min after stimulation onset. During the following 1.5--2 min, blood flow decreased at all sites with a tendency to return to baseline towards the end of the observation period. Except for BP and peripheral blood flow, all of the cardiovascular changes exhibited significant changes during the observation period; no differences between groups were detected. When compared to healthy controls BMS patients generally exhibited larger changes in mBF. These changes were significant for recordings made on the hard palate (F[1,24]=13.9, P<0.001). Dry ice stimulation appears to be an effective, non-invasive and reasonably tolerable means to investigate mucosal blood flow at different mucosal sites. In general, vasoreactivity in BMS patients was higher than in healthy controls. BMS patients exhibited a higher response on the hard palate compared to controls. These changes in oral blood flow appear to be specifically related to BMS symptoms indicating a disturbed vasoreactivity. PMID- 11207399 TI - Bee venom injection into an acupuncture point reduces arthritis associated edema and nociceptive responses. AB - Bee venom (BV) has traditionally been used in Oriental medicine to relieve pain and to treat inflammatory diseases such as rheumatoid arthritis (RA). While several investigators have evaluated the anti-inflammatory effect of BV treatment, the anti-nociceptive effect of BV treatment on inflammatory pain has not been examined. Previous studies in experimental animals suggest that the therapeutic effect of BV on arthritis is dependent on the site of administration. Because of this potential site specificity, the present study was designed to evaluate the anti-nociceptive effect of BV injections into a specific acupoint (Zusanli) compared to a non-acupoint in an animal model of chronic arthritis. Subcutaneous BV treatment (1 mg/kg per day) was found to dramatically inhibit paw edema caused by Freund's adjuvant injection. Furthermore, BV therapy significantly reduced arthritis-induced nociceptive behaviors (i.e. the nociceptive scores for mechanical hyperalgesia and thermal hyperalgesia). These anti-nociceptive/anti-inflammatory effects of BV were observed from 12 days through 21 days post-BV treatment. In addition, BV treatment significantly suppressed adjuvant-induced Fos expression in the lumbar spinal cord at 3 weeks post-adjuvant injection. Finally, injection of BV into the Zusanli acupoint resulted in a significantly greater analgesic effect on arthritic pain as compared to BV injection in to a more distant non-acupoint. The present study demonstrates that BV injection into the Zusanli acupoint has both anti inflammatory and anti-nociceptive effects on Freund's adjuvant-induced arthritis in rats. These findings raise the possibility that BV acupuncture may be a promising alternative medicine therapy for the long-term treatment of rheumatoid arthritis. PMID- 11207401 TI - A selective increase in Fos expression in spinal dorsal horn neurons following graded thermal stimulation in rats with experimental mononeuropathy. AB - In order to clarify the central mechanisms of thermal hyperalgesia produced by peripheral nerve injury, Fos protein-like immunoreactive (Fos-LI) cells in spinal dorsal horn neurons were studied in rats with chronic constriction nerve injury (CCI) following graded thermal stimulation of the hind paw. The graded thermal stimuli (cold: 5, 10 and 15 degrees C, heat: 42, 46 and 54 degrees C) were applied to the plantar surface of the operated hind paw 14 days after CCI or sham operation, and the number of Fos-LI cells in the spinal dorsal horn was quantified. Many Fos-LI cells were expressed in the superficial laminae of the spinal dorsal horn both in sham-operated and CCI rats following thermal stimulation. Fos-LI cells were mainly restricted to the medial half of the superficial laminae of the spinal dorsal horn, and were sparsely distributed in the deeper laminae. The number of Fos-LI cells in the superficial laminae (laminae I--II) of the dorsal horn was significantly higher in CCI rats after stimulation at 10 and 46 degrees C, but not at the other stimulating temperatures (5, 15, 42, and 54 degrees C) as compared to that in sham-operated rats. In laminae III-IV, the number of Fos-LI cells was significantly higher at all stimulus temperatures in CCI rats when compared to the sham-operated rats. No distribution difference of Fos-LI cells was observed between CCI and sham operated rats in laminae V--VI. Thus, in the spinal dorsal horn of the CCI rats, there was a selective increase in thermal stimulus-induced Fos-LI cells in the superficial dorsal horn after stimulating at near noxious threshold intensities and a non-selective increase in Fos-LI cells in laminae III--IV after both noxious and innocuous thermal stimuli. The increase of Fos-LI cells in the superficial laminae may be related to hypersensitivity to noxious stimuli while the increase of Fos-LI cells in laminae III--IV may be related to an increased sensitivity to both noxious and innocuous stimuli that leads to increased reflex activity following nerve injury. PMID- 11207402 TI - Emergency Department compression ultrasound to diagnose proximal deep vein thrombosis. AB - Emergency Department (ED) patients with suspected deep vein thrombosis (DVT) require an objective vascular study such as ultrasound (US) to confirm the diagnosis prior to treatment or disposition. A simple compression US test of the common femoral vein and popliteal vein reliably detects proximal DVT in symptomatic patients. Application of compression US in the ED by Emergency Physicians (EPs) has been tested in a single previous study. We evaluated the ability of ED compression US, performed by EPs, to diagnose proximal DVT as compared to duplex US performed in a vascular laboratory. A prospective, observational study was conducted on a convenience sample of patients presenting to an ED with lower extremity symptoms and signs suggestive of DVT. Patients with a history of DVT in the symptomatic extremity were excluded. Final diagnosis of DVT was made by color-flow duplex US performed in a vascular laboratory. ED compression US was performed by one of six EP sonographers. In compression US, DVT was diagnosed by the inability to compress the common femoral vein or popliteal vein. The examination was considered indeterminate if the veins could not be clearly identified or compressibility was equivocal. For statistical analysis, an indeterminate examination was considered positive. In those cases where ED compression US was discordant with duplex US, and not indeterminate, we retrospectively reviewed the US findings. There were 76 patients who completed the study, and 18 patients (24%) were diagnosed with DVT by duplex US, among whom ED compression US was positive in 14, negative in 2, and indeterminate in 2. Among 58 patients diagnosed without DVT by duplex US, there were 4 false-positive ED compression US examinations and 10 indeterminate examinations. In all, ED compression US was indeterminate in 12 patients (15.8%). Compared to duplex US, ED compression US had a sensitivity of 88.9% (95% C.I. 65.3-98.6%) and specificity of 75.9% (62.8-86.1). Negative predictive value was 95.7% (85.2 99.5). Among ED patients with the clinical diagnosis of possible DVT, negative ED compression US greatly reduces the likelihood of DVT, such that discharge and outpatient follow-up can be considered. Because of limited specificity, positive results require confirmation, but may justify immediate treatment pending follow up testing. Indeterminate results can be expected in a significant number of patients and mandate further testing prior to disposition. PMID- 11207403 TI - Slow infusion for the prevention of akathisia induced by prochlorperazine: a randomized controlled trial. AB - The utility of intravenous prochlorperazine (PCZ) in the treatment of nausea, vomiting, and headache may be limited by the akathisia that occurs frequently with the recommended 2-min infusion rate. We tested the hypothesis that decreasing the rate of PCZ infusion to 15 min reduces the incidence of akathisia at 1 hour. This double-blinded, randomized, controlled trial was conducted in the Emergency Department of an academic tertiary-care medical center with an annual census of 95,000 emergency patient visits. We enrolled a convenience sample of adult patients who received 10 mg i.v. PCZ for the treatment of nausea, vomiting, or headache. Subjects were randomized to receive either a 2-min infusion of PCZ (10 mg) followed by a 15-min infusion of saline, or a 2-min infusion of saline followed by a 15-min infusion of prochlorperazine. The incidence of akathisia at 1 hour was measured by using explicit diagnostic criteria. One hundred sixty patients were randomly enrolled into two groups, which were comparable with respect to age, gender, weight, and complaint. Akathisia developed in 31 of 84 patients (36.9%) who received the 2-min infusion of PCZ and in 18 of 76 patients (23.7%) who received the 15-min infusion of PCZ (p = 0.07), a 36% (95% CI, -5% to 61%) relative reduction. The delta from pre-infusion to postinfusion scores between the two groups was not significant (p = 0.19). We conclude that slowing the rate of PCZ infusion does not decrease akathisia. PMID- 11207404 TI - A prospective study comparing i.m. ketorolac with i.m. meperidine in the treatment of acute biliary colic. AB - Ketorolac is a nonsteroidal anti-inflammatory medication that is used widely for pain management. Its effects are mediated through the inhibition of prostaglandins, which makes it uniquely different from opioids in relieving pain. We conducted a randomized, prospective, double blind study of patients presenting to our Emergency Department (ED) with a diagnosis of acute biliary colic. Study patients were randomized into one of two treatment groups, meperidine 1.5 mg/kg with a maximum dose of 100 mg or ketorolac 60 mg given intramuscularly (i.m.). The patients rated their pain before and 30 min after medication on a scale of 1 to 10 using a Visual Analog Pain Scale. Overall pain relief was compared between the two groups using a two-sample t test. Thirty patients were enrolled in the study, 16 in the ketorolac group and 14 in the meperidine group. Patients ranged in age from 18 to 71 years and 6 (20%) were male. The average pain score at time 0 was 7.6 for the ketorolac group and 7.3 for the meperidine group. Pain relief at time 30 min was 3.8 in the ketorolac group and 3.9 in the meperidine group, which was not statistically different. The mean global pain score and need for an emergency cholecystectomy were similar in the two groups. Rescue medication for additional analgesia at 30 min was needed in 4 patients in the meperidine group and in 2 patients in the ketorolac group (28.6% versus 12.5%, respectively; NS). In this study of patients with acute biliary colic there was no significant difference in the pain relief achieved by using either ketorolac or meperidine. PMID- 11207405 TI - Corneal bee sting with retained stinger. AB - Bee stings of the cornea are rarely reported, but have the potential for causing serious ophthalmologic injuries. We present a case of corneal bee sting with retained stinger apparatus and associated iritis and discuss the pathologic mechanisms of injury, evaluation, and treatment of these uncommon presentations. PMID- 11207406 TI - Airbags and bilateral eye injury: five case reports and a review of the literature. AB - We report five cases of bilateral eye injuries from airbag deployment in motor vehicle crashes and review the world's literature on ocular injuries associated with airbags. The cases in the literature were identified by cross-referencing Medline searches from airbags and ocular injuries. Additional cases were identified after review of references from each article in the search. An additional 89 cases from the literature were identified and are included for discussion. Patients were treated individually in a noncontrolled, nonrandomized fashion according to the nature of each injury with regular follow-up examinations in clinic. Of the 94 cases studied, 24 (27%) were bilateral eye injuries, and 15 (16%) patients were wearing spectacles at the time of the accident. The most common injuries included corneal abrasions, eyelid trauma, and hyphemas. Outcomes ranged from complete resolution of symptoms and return of normal visual acuity to primary enucleation. This report describes the wide spectrum of eye injuries that may occur after airbag deployment. We suggest a management plan for the evaluation and treatment of the ocular complications of airbag-related trauma. PMID- 11207407 TI - Three common presentations of ascariasis infection in an urban Emergency Department. AB - In the United States, approximately 4 million people per year are infected with Ascaris lumbricoides. We reviewed the common presentations of complications of Ascariasis infection in the Emergency Department (ED) and the diagnostic tools and treatment available. This was a retrospective case review conducted on all patients diagnosed with Ascariasis (using ICD-9 codes) over a 6-year period at Los Angeles County and University of Southern California Medical Center. Three patients with distinct complications secondary to Ascariasis were chosen, and all ED and inpatient records were reviewed. The patient's age, sex, race, presenting symptoms, data, outcome, and ED course and diagnosis were recorded. The three cases included a periappendiceal abscess, Loeffler's syndrome, and biliary colic/choledocholithiasis. The first patient underwent a computed tomography guided drainage of the abscess. The second patient received supportive care and antibiotic therapy secondary to a superimposed bacterial pneumonia. The third patient underwent endoscopic retrograde cholangiopancreatography with sphincterotomy. All three patients had a stool ova and parasites positive for A. lumbricoides, and all received a 3-day course of mebendazole. Symptomatic cases of Ascariasis may present to EDs in the United States. Important diagnostic tools for the ED include chest X-ray, X-ray of the kidney-ureter-bladder and ultrasonography. Single-dose medications given in the ED are very effective in eradicating A. lumbricoides infection, thus avoiding hospitalization. PMID- 11207408 TI - Twenty-foot fall averts fatality from massive hydrogen sulfide exposure. AB - Hydrogen sulfide is a colorless irritant and asphyxiant gas with a noxious odor of "rotten eggs." Acute hydrogen sulfide exposure may cause, depending on the level and duration of toxicity, symptoms ranging from mild mucous membrane irritation to permanent neurologic impairment and cardiopulmonary arrest. We present a case of an oil refinery worker exposed to a typically fatal concentration of hydrogen sulfide gas (>1000 ppm) while working on top of a 20 foot ladder. The "knockdown" effect of exposure to high concentrations of hydrogen sulfide caused him to lose consciousness and fall from the top of the ladder. He was transported to the Emergency Department as a major trauma victim. Ironically, this 20-foot fall saved his life and possibly those of the rescuers by immediately removing him from the source of the hydrogen sulfide. Treatment of hazardous materials incidents and the pathophysiology and treatment options for hydrogen sulfide poisoning are discussed. PMID- 11207409 TI - Electrocardiographic manifestations: digitalis toxicity. AB - Toxicity from the digitalis family of cardiac glycoside medications remains common. Successful treatment depends on early recognition; however, the diagnosis of potentially life-threatening toxicity remains difficult because the clinical presentation is often nonspecific and subtle. The hallmark of cardiac toxicity is increased automaticity coupled with concomitant conduction delay. Though no single dysrhythmia is always present, certain aberrations such as frequent premature ventricular beats, bradydysrhythmias, paroxysmal atrial tachycardia with block, junctional tachycardia, and bidirectional ventricular tachycardia are common. Treatment depends on the clinical condition rather than serum drug level. Management varies from temporary withdrawal of the medication to administration of digoxin-specific Fab fragments for life-threatening cardiovascular compromise. PMID- 11207410 TI - A rare cause of congestive heart failure. PMID- 11207411 TI - Penile incarceration: a wrapping technique. PMID- 11207412 TI - Sinus arrest or sinoventricular conduction in mild hyperkalemia. PMID- 11207413 TI - Lung abscess. PMID- 11207414 TI - 5th Annual David R. Boyd, MD Lecture: Revolutionary advances in wound repair in emergency medicine during the last three decades. A view toward the new millennium. AB - This lecture provides an overview of advances in wound repair devised by our multidisciplinary team of physicians, scientists, and students. Our collective efforts have devised products, drugs, and concepts that are facilitating wound repair without infection and with the least possible scar. Some of the beneficial products and drugs developed or identified by our laboratory include nitrile examination and surgical gloves, magnification loupes, high pressure syringe irrigation, Shur Clens, as well as a wide variety of different wound closure techniques. In addition, our studies of the mechanism of wound injury, soil infection-potentiating fractions, dynamic and static skin tensions, and microflora of the skin have become important predictors of the outcomes of wound repair. During the new millennium, the computerized clinical information system as well as studies of tissue regeneration should dramatically change our approaches to wound repair. PMID- 11207416 TI - The diagnosis. PMID- 11207415 TI - Using Q methodology to assess the needs of emergency medicine support staff employees. AB - The support staff members of any Department of Emergency Medicine perform a plethora of tasks that are crucial to the productivity of both individual physicians and the department as a whole. It is important to ensure that the personal and professional needs of the support staff are being met. This report describes the use of a relatively new statistical technique, Q methodology, to elucidate the needs of the support staff. This method allowed the investigators to quantitatively reveal the presence of two distinct viewpoints on employee needs among the support staff. Additionally, opinions that were held by the employees concerning their needs were identified. These results allowed for strategies to be tailored to both the individual and the group. The results indicate that Q methodology can have widespread application in the relatively new area of health care quality research. PMID- 11207417 TI - Pearls of wisdom for your emergency medicine rotation. PMID- 11207419 TI - Dopaminergic innervation of human basal ganglia. AB - This paper summarises the results of some of our recent tyrosine hydroxylase (TH) immunohistochemical studies of the dopaminergic innervation of the human basal ganglia. It also reports new findings on the presence of TH-immunoreactive (ir) neurons in the striatum. Our data show the existence of nigrostriatal TH-ir axons that provide collaterals arborizing in the globus pallidus and subthalamic nucleus. These thin and varicose collaterals emerge from thick and smooth axons that course along the main output pathways of the basal ganglia, including the ansa lenticularis, the lenticular fasciculus and Wilson's pencils. We postulate that this extrastriatal innervation, which allows nigral dopaminergic neurons to directly affect the pallidum and subthalamic nucleus, plays a critical role in the functional organisation of human basal ganglia. The TH-ir fibres that reach the striatum arborize according to a highly heterogeneous pattern. At rostral striatal levels, numerous small TH-poor zones embedded in a TH-rich matrix correspond to calbindin-poor striosomes and calbindin-rich extrastriosomal matrix, respectively. At caudal striatal levels, in contrast, striosomes display a TH immunostaining that is more intense than that of the matrix. A significant number of small, oval, aspiny TH-ir neurons scattered throughout the rostrocaudal extent of the caudate nucleus and putamen, together with a few larger, multipolar, spiny TH-ir neurons lying principally within the ventral portion of the putamen, were disclosed in human. This potential source of intrinsic striatal dopamine might play an important role in the functional organisation of the human striatum, particularly in case of Parkinson's disease. PMID- 11207420 TI - The use of cerebral blood flow as an index of neuronal activity in functional neuroimaging: experimental and pathophysiological considerations. AB - Over recent years, activation studies that have been undertaken using brain imaging techniques, such as functional magnetic resonance imaging, positron emission tomography or near infrared spectroscopy, have greatly improved our knowledge of the functional anatomy of the brain. Nevertheless, activation studies do not directly quantify the variations of synaptic transmission (neuronal activity) but detect it indirectly either through the visualisation of changes in cerebral blood flow, oxidative or glycolytic metabolism (for positron emission tomography), or through the measurement of a global index that is dependent on both cerebral blood flow and oxidative metabolism (for functional magnetic resonance imaging and near infrared spectroscopy). Such approaches are based on the concept of a tight parallelism--termed coupling--between variations in neuronal activity, metabolism and cerebral blood flow. However, several "uncoupled" situations between these parameters have been reported over the last decade through experimental, pharmacological and pathophysiological studies. The aim of this review is to focus on these data that have to be taken into account for the interpretation of the results obtained in activation paradigms. PMID- 11207421 TI - New insights into genetic and molecular mechanisms of brain degeneration in tauopathies. AB - Abundant neurofibrillary lesions consisting of the microtubule associated protein tau and amyloid beta peptide deposits are the defining lesions of Alzheimer's disease. Prominent filamentous tau pathology and brain degeneration in the absence of extracellular amyloid deposition characterize a number of other neurodegenerative disorders (i.e. progressive supranuclear palsy, corticobasal degeneration, Pick's disease) collectively referred to as tauopathies. The discovery of multiple tau gene mutations that are pathogenic for hereditary frontotemporal dementia and parkinsonism linked to chromosome 17 in many kindreds, as well as the demonstration that tau polymorphisms are genetic risk factors for sporadic tauopathies, directly implicate tau abnormalities in the onset/progression of neurodegenerative disease. Different tau gene mutations may be pathogenic by impairing the functions of tau or by perturbing the splicing of the tau gene, thereby resulting in biochemically and structurally distinct tau aggregates. However, since specific polymorphisms and mutations in the tau gene lead to diverse phenotypes, it is plausible that additional genetic or epigenetic factors influence the clinical and pathological manifestations of both familial and sporadic tauopathies. Thus, efforts to develop animal models of tau-mediated neurodegeneration should provide further insights into the onset and progression of tauopathies as well as Alzheimer's disease, and they could accelerate research to discover more effective therapies for these disorders. PMID- 11207422 TI - Alpha-synuclein is not a requisite component of synaptic boutons in the adult human central nervous system. AB - It is increasingly clear that the normal protein alpha-synuclein is in some manner closely associated with presynaptic components of select neuronal types within the adult human central nervous system (CNS) and, in addition, that in its pathologically altered state alpha-synuclein aggregates selectively in the form of filamentous inclusion bodies during certain progressive neurodegenerative disorders, such as familial and sporadic Parkinson's disease. By having the antibody AFshp raised specifically to alpha-synuclein to label Parkinson disease specific Lewy bodies and Lewy neurites as well as synaptic boutons containing the unaltered protein, an initial attempt is made to map the overall distribution pattern and describe the staining behavior of the immunoreactive punctae in select regions of the prosencephalon. Neocortical immunolabeling is most prominent in the prodigious, but incompletely myelinated, association fields and faintest in the heavily myelinated primary motor and primary sensory fields, with the premotor and first order sensory association areas occupying an intermediate position. Of the thalamic grays evaluated, those containing powerfully myelinated fiber tracts (e.g. centrum medianum, habenular complex) show the weakest immunolabeling, whereas, less sturdily myelinated structures are highly immunoreactive. The fact that the immunostaining spectrum for normal alpha synuclein is so broad, together with the fact that some thalamic sites actually are immunonegative leads to the following conclusions (1) alpha-synuclein, although present in the synaptic boutons of many nerve cells in the adult human CNS, is by no means ubiquitous there, and (2) neuronal types lacking the normal protein cannot generate the Parkinson's disease-specific filamentous pathology. PMID- 11207424 TI - Glutamate decarboxylase(65)-immunoreactive terminals in cingulate and prefrontal cortices of schizophrenic and bipolar brain. AB - Recent postmortem studies have been suggesting that a defect of GABAergic neurotransmission might occur in the corticolimbic system of subjects with schizophrenia and bipolar disorder. To explore this possibility, a method for immunolocalizing the 65 kdalton isoform of glutamate decarboxylase (GAD(65)) has been developed and applied to the anterior cingulate (ACCx) and prefrontal (PFCx) cortices of 12 normal controls (CONs), 12 schizophrenics (SZs) and 5 manic depressive (MDs) subjects. A computer-assisted technique was employed under strictly blind conditions to determine the density of GAD(65)-IR terminals in apposition with pyramidal (PNs) and nonpyramidal (NPs) neurons and in neuropil (NPL) of layers II, III, V and VI of each cortical region. For SZs, no difference in the numerical density of GAD(65)-IR terminals in contact with either PNs or NPs or in NPL of layers II-VI in ACCx or PFCx was detected. There were also no differences in the size of either PNs and NPs that could have influenced the nature of these findings. Using a pixel count analysis, the size of IR terminals was, however, found to be increased in layers II (10.3%) and III (15.8%) of SZs, but only in subjects treated with neuroleptic drugs. For MDs, the density of GAD(65)-IR terminals was significantly reduced in all four layers of ACCx, but these differences were most significant in layers II (27.8%) and III (37.2%), whether or not the subjected were treated with neuroleptics. In PFCx, the MDs showed similar differences in terminal density for PNs and NPs but not neuropil in the four laminae examined. The MD group showed no differences in either the size of cell bodies or IR terminals. Age and PMI did not account for any of the differences between the CONs vs SZs and MDs. Overall, the results of this study, though preliminary, suggest that there may be complex changes in GABAergic terminals in SZ and MD, ones that may vary with respect to primary diagnosis and neuroleptic exposure. PMID- 11207423 TI - Crosslinking of alpha-synuclein by advanced glycation endproducts--an early pathophysiological step in Lewy body formation? AB - An excess of reactive carbonyl compounds (carbonyl stress) and their reaction products, advanced glycation endproducts (AGEs), are thought to play a decisive role in the pathogenesis of neurodegenerative disorders and Parkinson's disease (PD) in particular. Accumulation of AGEs in various intracellular pathological hallmarks of PD, such as Lewy bodies, densely crosslinked intracellular protein deposits formed from neurofilament components and alpha-synuclein, have already been described in patients in advanced stages of the disease. There is, however, no indication of the involvement of AGE-induced crosslinking of alpha-synuclein in very early stages of the disease. In this study, we observed that AGEs and alpha-synuclein are similarly distributed in very early Lewy bodies in the human brain in cases with incidental Lewy body disease. These cases might be viewed as pre-Parkinson patients, i.e. patients who came for autopsy before the possible development of clinical signs of PD. AGEs are both markers of transition metal induced oxidative stress as well as, inducers of protein crosslinking and free radical formation by chemical and cellular processes. Thus, it is likely that AGE promoted formation of Lewy bodies reflects very early causative changes rather than late epiphenomenons of PD. PMID- 11207425 TI - Serotonin transporters upregulate with chronic cocaine use. AB - Cocaine potently inhibits serotonin (5-HT) reuptake in cell bodies and at nerve terminals and 5-HT has been implicated as a modulator of dopaminergic neurotransmission. Chronic use of cocaine may lead to a "serotonin-deficit" form of 5-HT dysregulation. We have examined the status of the 5-HT transporter (SERT) using ligand binding and autoradiographic methods in subgroups of cocaine overdose deaths. Quantitative autoradiography of [125I]RTI-55 was used to map and measure the effect of chronic cocaine use on SERT densities in the striatum, substantia nigra, amygdala, and adjacent paralimbic cortical areas of cocaine overdose (CO) victims with and without preterminal evidence of excited delirium (ED). SERT densities were elevated in the nucleus accumbens and throughout the anterior and posterior sectors of striatum in CO victims compared with age matched and drug-free control subjects. In contrast, SERT densities were increased significantly in the anterior striatum, but not the posterior sectors in ED victims. Significant elevations in SERT were measured in the orbitofrontal gyrus (Brodmann area 11), the anterior portion of the insular cortex and the cingulate gyrus (Brodmann area 24) in CO and ED victims. Saturation binding site analysis demonstrated an increase in the density of RTI-55 binding sites with no change in the affinity of the radioligand for the SERT. Chronic cocaine exposure upregulated SERT densities in the substantia nigra of the CO, but not ED victims. The lack of SERT upregulation in the substania nigra and posterior striatum suggests the possibility of a distinct phenotype for fatal ED victims that exhibited an acute onset of bizarre and violent behavior prior to death. Adaptive changes in the SERT densities may contribute to depressed mood and drug craving associated with acute cocaine abstinence. PMID- 11207426 TI - Nicotinic receptors in human brain: topography and pathology. AB - Brain nicotinic acetylcholine receptors (nAChR) are a class of ligand-gated channels composed of alpha and beta subunits with specific structural, functional and pharmacological properties. They participate in the physiological and behavioural effects of acetylcholine and mediate responses to nicotine. They are associated with numerous transmitter systems and their expression is altered during development and ageing as well as in diseases such as autism, schizophrenia, Alzheimer's disease, Parkinson's disease and Lewy body dementia. Nicotinic receptors containing a number of different subunits are highly expressed during early human development. Disorders believed to be associated with abnormal brain maturation involve deficits in both alpha4beta2, in the case of autism, and alpha7 possibly in addition to alpha4beta2 nAChRs in the case of schizophrenia. In ageing and age-related neurodegenerative disorders nAChR deficits are predominantly associated with alpha4-containing receptors, although some studies also indicate the involvement of alpha3 and alpha7 subunits. Whilst ageing appears to be associated with reductions in subunit mRNA as well as protein expression, in Alzheimer's disease only protein loss is apparent. Nicotinic therapy may be of benefit in a number of neurological conditions, however studies evaluating further both the distribution of specific subunit involvement and the correlation of nAChR deficits with clinical symptoms are required to inform therapeutic strategy. PMID- 11207427 TI - The alpha7-nicotinic acetylcholine receptor and the pathology of hippocampal interneurons in schizophrenia. AB - This paper is a review of a recent findings on the pathology of hippocampal interneurons in schizophrenia, with specific emphasis on a protein expressed by these cells, the alpha7-nicotinic acetylcholine receptor subunit. Convergent information indicates that interneurons in the hippocampus and other forebrain structures are decreased in number and function in subjects with schizophrenia. Among the neurochemical markers that are decreased in the hippocampus are synapsin I, cholecystokinin, somatostatin, glutamic acid decarboxylase, and nitric oxide synthase. GABA uptake sites and the GABA synthetic enzyme glutamic acid decarboxylase are also diminished. Included among these findings is decreased binding of alpha-bungarotoxin, which binds to low-affinity nicotinic acetylcholine receptors, such as the alpha7-nicotinic receptor. Co-labeling experiments in rodents indicate that these markers are expressed on overlapping populations of hippocampal interneurons. Thus, the finding of decreased neurochemical function of hippocampal interneurons is a widely replicated finding, with different groups reporting markedly similar findings using independent post mortem samples and different neurochemical strategies. Decreased alpha-bungarotoxin binding or decreased alpha7-nicotinic receptor immunoreactivity has also been found in the frontal cortex and in the nucleus reticularis thalami of schizophrenic subjects. The alpha7-nicotinic receptor subunit gene on chromosome 15q14 is a site of heritability for schizophrenia and bipolar affective disorder, and in, particular, for a deficit in inhibitory neuronal function associated with these illnesses. Thus, the post mortem data are further supported by psychophysiologic and genetic investigations that indicate a deficit in inhibitory interneuronal function, involving the alpha7-nicotinic receptor. The alpha7-receptor is a ligand-gated ion channel that admits calcium ions into cells, and it has been proposed to have various developmental roles. Its malfunction may be part of the developmental pathogenesis of schizophrenia. PMID- 11207428 TI - Ontogeny of the dopamine D2 receptor mRNA expressing cells in the human hippocampal formation and temporal neocortex. AB - The study details the cellular expression of the dopamine D2 receptor mRNA in the human temporal lobe during prenatal development. At 13 embryonic weeks (E13) D2 mRNA was widely expressed in the temporal lobe. At this time point in the dentate gyrus D2 mRNA positive cells first appeared at the outer border of the granular layer and their number increased with development. The CA1 exhibited the highest level of D2 mRNA expression. By E19-25 the hippocampal formation underwent rapid morphological maturation. D2 mRNA expression became more uniform and dense in the ammonic subfield. At all ages the subiculum appeared more mature morphologically but less intensely stained for D2 mRNA than the ammonic fields. In the entorhinal cortex D2 mRNA expression was most conspicuous in the future layer II at all ages. In the temporal neocortex D2 mRNA-positive cells were detected in the subplate and cortical plate. Differentiation of the cortical plate was accompanied by concentration of D2 mRNA-positive cells in layer V. The most conspicuous cells expressing D2 mRNA were found in the marginal zone of all regions and resembled Cajal-Retzius cells in morphology and location. Density of putative Cajal-Retzius cells expressing D2 mRNA decreased with development. They all but disappeared from the hippocampal areas by mid gestation, but in the temporal neocortex occasional cells were seen even at term. Early and widespread but region and cell type specific expression of D2 receptor mRNA suggests an important role of this DA receptor subtype in prenatal development of the human temporal lobe. PMID- 11207429 TI - Characterization of NPY mRNA-expressing cells in the human brain: co-localization with Y2 but not Y1 mRNA in the cerebral cortex, hippocampus, amygdala, and striatum. AB - Neuropeptide Y (NPY) is one of the most abundant peptides in the central nervous system. Its effects on, for example, cognition, memory and motor functions are thought to be mediated mainly via its interactions with the NPY Y1 and Y2 receptor subtypes. We had previously described the neuroanatomical organization of the Y1 and Y2 mRNA expression in humans. However, in view of the lack of information regarding the overall detailed distribution of NPY mRNA expression in the human brain, a complete picture of the anatomical organization of the NPY related genes was still missing. Thus, in the present study, the regional distribution of NPY mRNA-expressing cells was analyzed in the post-mortem human brain. In addition, double labeling in situ hybridization was performed to characterize the NPY neuronal populations in relation to the Y1 and/or Y2 receptor mRNA localization in the human cerebral cortex, striatum, and amygdala. NPY mRNA was found to be abundant in layers II and VI of the neocortex, polymorphic layer of the dentate gyrus, basal ganglia, and amygdala. Double labeling in situ hybridization showed the co-expression of NPY mRNA with the Y2, but not with the Y1, mRNA in the human cerebral cortex, hippocampus, amygdala, striatum, and nucleus accumbens, and the existence of co-expression of the Y1 and Y2 mRNAs in the cerebral cortex and amygdala. Overall, these results suggest a role for the Y2, but not Y1, as an autoreceptor in the NPY neuronal populations of the human brain. PMID- 11207430 TI - Distribution of angiotensin IV binding sites (AT4 receptor) in the human forebrain, midbrain and pons as visualised by in vitro receptor autoradiography. AB - Angiotensin IV and other AT4 receptor agonists, improve memory retention and retrieval in the passive avoidance and swim maze learning paradigms. Angiotensin IV binding sites (also known as the AT4 receptors) are widely distributed in guinea pig and monkey (Macaca fascicularis) brains where high densities of the binding sites have been detected in the hippocampus, neocortex and motor nuclei. However, the distribution of the binding sites in the human brain is not known. We have recently localised the angiotensin IV binding sites (AT4 receptors) in post-mortem human brain using iodinated Nle-angiotensin IV, a higher affinity and more stable analogue of angiotensin IV. This radioligand bound with relatively high affinity and specificity to angiotensin IV binding sites. In competition studies on consecutive sections through the prefrontal cortex and claustrum, angiotensin IV, Nle-angiotensin IV and LVV-hemorphin 7 competed for the binding of 125I[Nle]-angiotensin IV with nanomolar affinities. Angiotensin II and the AT1 and AT2 receptor antagonists were ineffective in competing for the binding at concentrations of up to 10 microM. We found high densities of 125I[Nle] angiotensin IV binding sites throughout the cerebral cortex including the insular, entorhinal, prefrontal and cingulate cortices. Very high densities of the binding sites were observed in the claustrum, choroid plexus, hippocampus and pontine nucleus. Some thalamic nuclei displayed high densities of binding including the anteroprincipal, ventroanterior, anteromedial, medial dorsal and ventrolateral nuclei. The caudate nucleus, putamen, many amygdaloid nuclei and the red nucleus all displayed moderate densities of binding with a higher level detected in the substantia nigra pars compacta. In the hypothalamus, high densities binding sites were found in the ventromedial nucleus with lower levels in the dorsomedial and paraventricular nuclei. The distribution of 125I[Nle] angiotensin IV binding sites in the human brain is similar to that found in other species and supports multiple roles for the binding sites in the central nervous system, including facilitation of memory retention and retrieval. PMID- 11207431 TI - Phosphodiesterase type 4 isozymes expression in human brain examined by in situ hybridization histochemistry and[3H]rolipram binding autoradiography. Comparison with monkey and rat brain. AB - We have examined the distribution of four different cyclic AMP-specific phosphodiesterase isozyme (PDE4A, PDE4B, PDE4C and PDE4D) mRNAs in the brain of different species by in situ hybridization histochemistry and by autoradiography with [3H]rolipram. We have compared the localization of each isozyme in human brain with that in rat and monkey brain. We have found that the four PDE4 isoforms display a differential expression pattern at both regional and cellular level in the three species. PDE4A, PDE4B and PDE4D are widely distributed in human brain, with the two latter appearing more abundant. In contrast, PDE4C in human brain, presents a more restricted distribution, limited to cortex, some thalamic nuclei and cerebellum. This is at variance with the distribution of PDE4C in rat brain, where it is found exclusively in olfactory bulb. In monkey brain, the highest expression for this isoform is found in the claustrum, and at lower levels in cortical areas and cerebellum. PDE4B presented a broad distribution, being expressed in both neuronal and non neuronal cell populations. In general, the distribution of binding sites visualized with [3H]rolipram correlated well with the expression of each PDE4 isozyme. PMID- 11207432 TI - Expression of the purported sigma(1) (sigma(1)) receptor in the mammalian brain and its possible relevance in deficits induced by antagonism of the NMDA receptor complex as revealed using an antisense strategy. AB - Sigma (sigma) receptors have generated a great deal of interest on the basis of their possible role in psychosis, neuroprotection and various other behaviors including learning processes. The existence of at least two classes of sigma receptor binding sites (sigma(1) and sigma(2)) is now well established. The recent cloning of the mouse, guinea pig and human sigma(1) receptors has allowed the study of the discrete distribution of the sigma(1) receptor mRNA in rodent and human brain tissues using in situ hybridization. Overall, the sites of expression of specific sigma(1) receptor mRNA signals were in accordance to the anatomical distribution of sigma(1) receptor protein first established by quantitative receptor autoradiography. Specific sigma(1) receptor hybridization signals were found to be widely, but discretely distributed, in mouse and guinea pig brain tissues. The highest levels of transcripts were seen in various cranial nerve nuclei. Lower, but still high hybridization signals were observed in mesencephalic structures such as the red nucleus, periaqueductal gray matter and substantia nigra, as well as in some diencephalic structures including such as the habenula and the arcuate, paraventricular and ventromedial hypothalamic nuclei. Superficial (I-II) and deeper (IV-VI) cortical laminae were moderately labeled in the mouse brain. Moderate levels of sigma(1) receptor mRNA were also found in the pyramidal cell layer and the dentate gyrus of the hippocampal formation. Other structures such as the thalamus and amygdaloid body also expressed the sigma(1) receptor mRNA although to a lesser extent. In murine peripheral tissues, strong hybridization signals were observed in the liver, white pulp of the spleen and the adrenal gland. In the postmortem human brain, moderate levels of sigma(1) receptor mRNA, distributed in a laminar fashion, were detected in the temporal cortex with the deeper laminae (IV-VI) being particularly enriched. In the hippocampal formation, the strongest hybridization signals were observed in the dentate gyrus while all other subfields of the human hippocampal formation expressed lower levels of the sigma(1) receptor mRNA. Antisense oligodeoxynucleotides against the purported sigma(1) receptor were used next to investigate the possible role of this receptor in dizocilpine (MK 801)/NMDA receptor blockade-induced amnesia. Following a continuous intracerebroventricular infusion of a specific sigma(1) receptor antisense into the third ventricle (0.4 nmol/h for 5 days), sigma(1)/[3H](+)pentazocine binding was significantly reduced in mouse brain membrane homogenates while a scrambled antisense control was without effect. Moreover, the sigma(1) receptor antisense treatments (5 nmol/injection, every 12 hx3 or 0.4 nmol/h for 5 days) attenuated (+)MK-801/NMDA receptor blockade-induced cognitive deficits in the treated mice while a scrambled antisense control had no effect. Taken together, these results demonstrate the widespread, but discrete, distribution of the sigma(1) receptor mRNA in the mammalian central nervous system. Moreover, antisense treatments against the purported sigma(1) receptor gene reduced specific sigma(1)/[3H](+)pentazocine binding and modulated cognitive behaviors associated with NMDA receptor blockade providing further evidence for the functional relevance of the cloned gene. PMID- 11207433 TI - The molecular basis of O2-sensing and hypoxia tolerance in pheochromocytoma cells. AB - Hypoxia is a common environmental stimulus. However, very little is known about the mechanisms by which cells sense and respond to changes in oxygen. Our laboratory has utilized the PC12 cell line in order to study the biophysical and molecular response to hypoxia. The current review summarizes our results. We demonstrate that the O2-sensitive K(+) channel, Kv1.2, is present in PC12 cells and plays a critical role in the hypoxia-induced depolarization of PC12 cells. Previous studies have shown that PC12 cells secrete a variety of autocrine/paracrine factors, including dopamine, norepinephrine, and adenosine during hypoxia. We investigated the mechanisms by which adenosine modulates cell function and the effect of chronic hypoxia on this modulation. Finally, we present results identifying the mitogen- and stress-activated protein kinases (MAPKs and SAPKs) as hypoxia-regulated protein kinases. Specifically, we show that p38 and an isoform, p38gamma, are activated by hypoxia. In addition, our results demonstrate that the p42/p44 MAPK protein kinases are activated by hypoxia. We further show that p42/p44 MAPK is critical for the hypoxia-induced transactivation of endothelial PAS-domain protein 1 (EPAS1), a hypoxia-inducible transcription factor. Together, these results provide greater insight into the mechanisms by which cells sense and adapt to hypoxia. PMID- 11207434 TI - Purification and characterization of superoxide dismutase from chicken liver. AB - Superoxide dismutase (SOD; EC 1.15.1.1) is an enzyme that protects against oxidative stress from superoxide radicals in living cells. This enzyme has been isolated, purified and partially characterized from chicken liver. The following steps were carried out in order to purify chicken liver SOD. Initially, the liver was homogenized and hemoglobin was removed. Subsequently protein precipitation was effected with (NH(4))(2)SO(4), methanol, (NH(4))(2)SO(4)-methanol and polyethylene glycol methods. The product from polyethylene glycol-3350 precipitation was found to have the highest SOD activity. Polyethylene glycol was removed by chromatography using a PD-10 column. After passing through an ultrafilter, the superoxide dismutase was fractionated by DEAE-ion chromatography and then Sephadex G-75 gel filtration chromatography. During this purification procedure, a specific activity of 4818.2 IU/mg was reached, corresponding to 285.8-fold purification. The purified enzyme, which was characterized as cyanide sensitive SOD, contained two subunits having Cu and Zn elements with a molecular weight of 16000+/-500 for each. The optimum pH of purified CuZnSOD was determined to be 8.9. The enzyme was found to have good pH stability in the pH range 6.0-7.5 at 25 degrees C over a 2-h incubation period and displayed good thermal stability up to 45 degrees C at pH 7.4 over a 1-h incubation period. The SOD enzyme was not inhibited by DTT and beta-mercaptoethanol, but inhibited by CN(-) and H(2)O(2). In the presence of 2 mM iodoacetamide, the enzyme showed an approximately 40% activity loss. Finally, the inhibitory effect of ionic strength on SOD was also investigated. PMID- 11207435 TI - Morphological and biochemical characterization of mitochondria in Torpedo red blood cells. AB - A study is presented on the morphology and respiratory functions of mitochondria from Torpedo marmorata red blood cells. In vivo staining of red blood cells and transmission electron microscopy showed the existence of a considerable number of vital and orthodox mitochondria which decreased from young erythroblasts to mature erythrocytes from 60-50 to 30-20 per cell. In erythrocytes mitochondria exhibited a canonical, functional respiratory chain. The content and activity of cytochromes in erythrocytes were, however, significantly lower as compared to mammalian tissues. PMID- 11207436 TI - Dermatan sulfates of normal and scarred fascia. AB - We evaluated the composition of dermatan sulfates (DS) derived from 23 samples of normal and 23 samples of scarred fascia lata. We analyzed the molecular weight of intact DS chains and the length of chain regions comprising: (1) clusters of L iduronate-containing disaccharides ("iduronic sections"); (2) clusters of D glucuronate-containing disaccharides ("glucuronic sections"); and (3) copolymeric sections with both types of disaccharides. A portion of scarred fascia DS chains demonstrated higher molecular weight compared with those from normal tissue. Most disaccharides of DS chains derived from both fascia types form copolymeric segments - heterogeneous in size - with alternatively distributed single disaccharides with glucuronic residues and mainly single ones with iduronate. Only a small number of disaccharides form "glucuronic sections" of heterogeneous size or short "iduronic sections". However, the scarred fascia DS chains demonstrate an increased content of shorter "glucuronic sections" and shorter, often oversulfated, copolymeric segments. It seems that in normal fascia, the DS chain type with a single, long copolymeric region and a single, shorter "glucuronic section" is predominant, while in scarred tissue an increase in multidomain DS chain content may occur. PMID- 11207437 TI - Lactate dehydrogenase from the northern krill Meganyctiphanes norvegica: comparison with LDH from the Antarctic krill Euphausia superba. AB - Electrophoretic polymorphism of lactate dehydrogenase (LDH, EC 1.1.1.27) from abdominal muscle is reported in the northern krill Meganyctiphanes norvegica. In the population, from the Gullmarsfjord (west coast of Sweden), LDH was encoded for by two different Ldh-A* and -B* loci. The isoenzymes were named according to their electrophoretic mobilities. Ldh-A* locus was polymorphic. The allelic frequencies were a=0.99, a'=0.002, a"=0.004, a"'=0.004. The level of LDH polymorphism is low. Most individuals possess the same amount of two LDH homopolymers (LDH-A*(4) and LDH-B*(4)). The Meganyctiphanes norvegica LDH-A*(4) and LDH-B*(4) isoenzymes and the predominant LDH-A*(4) isoenzyme from Euphausia superba were purified to specific activities of 294, 306 and 464 micromol NADH min(-1) mg(-1), respectively. In both species the LDH isoenzymes were separated by chromatofocusing. All three isoenzymes are L-specific tetramers with molecular weight of approximately 160 kDa. Northern krill LDH-A*(4) has higher affinity for pyruvate and lactate and is more thermostable than LDH-B*(4). Both isoenzymes are inhibited significantly by high concentration of pyruvate but not lactate. Antarctic krill isoenzyme exhibits high substrate affinities, high NAD inhibition, high inhibition at 10 mM pyruvate, lack of lactate inhibition, and high heat stability and resembles northern krill LDH-A*(4) isoenzyme. PMID- 11207438 TI - Nitric oxide induces apoptosis in the fat body cell line IPLB-LdFB from the insect Lymantria dispar. AB - The presence of immunoreactive inducible nitric oxide synthase molecules (ir iNOS) is demonstrated in the Lymantria dispar IPLB-LdFB cell line. The maximum ir iNOS inducibility is observed 18 h after incubation with sodium nitroprusside (SNP). The increase in NO provoked by SNP in turn induces apoptosis. However, this phenomenon is observed only after 48 h. The NOS-inhibitors N(omega)-nitro-L arginine methyl ester (L-NAME) and N-[3-(aminomethyl)-benzyl]acetamide (1400W) were both unable to block the SNP-induced apoptosis at all the concentrations used. Incubation with SNP plus N-acetyl-L-cysteine (NAC) further augmented the percentage of cell death with respect to SNP used alone, and this process is seen earlier, i.e. after 24 h. Moreover, the induction of apoptosis in the presence of NAC is time- and concentration-dependent. The high percentage of cell death with SNP+NAC suggests that NAC forms S-nitrosothiols with NO, resulting in an increase in the bioavailability of NO. In conclusion, these findings show the existence of a close relationship between mammalian and invertebrate cells with regards to SNP and NAC induction and the related NO response. PMID- 11207439 TI - Effects of ration on somatotropic hormones and growth in coho salmon. AB - We examined the response of growth hormone (GH), total plasma insulin-like growth factor I (IGF-I), and growth rate to a change in ration in coho salmon. Tanks of individually tagged fish were placed on high, medium, or low ration, and sampled every 2 weeks for 8 weeks to create a range of growth rates. Some fish received non-lethal blood draws, while others were sampled terminally. Plasma IGF-I levels were higher in high ration fish than in low ration fish from 4 weeks after the beginning of experimental diets to the end of the experiment. GH levels were low and similar in all fish after changing rations, except for the fish in the low ration group at week 2. IGF-I was strongly correlated with specific growth rate in weight in terminally sampled fish after 4 weeks. GH did not correlate with growth rate or IGF-I levels. Growth parameters (length, weight, specific growth rates in weight and length, and condition factor) responded to ration. Serial sampling reduced growth rates and hematocrit, but did not change hormone levels. This study shows that IGF-I responds to changed rations within 2-4 weeks in salmonids. PMID- 11207440 TI - Antifreeze glycoproteins: relationship between molecular weight, thermal hysteresis and the inhibition of leakage from liposomes during thermotropic phase transition. AB - Antifreeze glycoproteins (AFGP) were isolated and purified from the blood plasma of rock cod (Gadus ogac), using DEAE-Bio-gel ion exchange chromatography, followed by high performance liquid chromatography (HPLC). The purified proteins were analyzed using polyacrylamide gel electrophoresis (PAGE), and electrospray mass spectrometry. The results indicated that rock cod synthesize seven size classes of glycoproteins, ranging from 2.6 to 24 kDa, with each size class containing multiple isoforms. Antifreeze activity, as determined by thermal hysteresis, indicated that the AFGP could be separated into two groups, with the larger size classes (molecular mass>13 kDa) having approximately 3-4 times the activity of the smaller, proline containing, size classes (molecular mass<10 kDa). All of the AFGP size classes prevented leakage from dielaidoylphosphatidylcholine (DEPC) liposomes as they were cooled through their phase transition temperature, with the larger size classes being approximately 4 times as effective as the smaller ones. It is hypothesized that AFGP prevent liposomes from leaking as they pass through the phase transition temperature by binding to the phospholipid membrane. PMID- 11207441 TI - Glucokinase is highly induced and glucose-6-phosphatase poorly repressed in liver of rainbow trout (Oncorhynchus mykiss) by a single meal with glucose. AB - The low dietary starch utilisation by rainbow trout (Oncorhynchus mykiss) may be attributed to a dysfunction of the nutritional regulation of the hepatic glucose/glucose-6-phosphate cycle. The present study was initiated to analyse the regulation of activity and gene expression of hepatic glucokinase (GK) and glucose-6-phosphatase (G6Pase) by dietary carbohydrates in this species. We found that even a single meal containing 24% of glucose is sufficient to induce the GK expression (mRNA and activity) as in mammals. In contrast, although the inhibitory effect of dietary glucose on G6Pase expression is observed at the molecular level, the G6Pase activity is not significantly inhibited by dietary glucose. Thus, in contrast to the gluconeogenic G6Pase enzyme, a rapid adaptation of the hepatic glycolytic GK enzyme to dietary glucose seems effective in rainbow trout. These results suggest that in carnivorous rainbow trout, the liver is capable to strongly regulate the utilisation of glucose but not the synthesis of glucose. PMID- 11207442 TI - Hyperlipidemia and reproductive failure in captive-reared alligators: vitamin E, vitamin A, plasma lipids, fatty acids, and steroid hormones. AB - Blood samples were collected from 26 captive-reared alligators (25 females; one male) and 12 (seven females and five males) wild "nuisance" alligators collected by wildlife personnel in south Louisiana in May 1995. The captive alligators, hatched from artificially incubated eggs in 1972-1973, had received vitamin E supplements during the 3 weeks before the blood sample was collected. Each sample was analyzed for vitamin E (alpha-tocopherol), vitamin A (retinol), total lipid, triacylglycerol, phospholipid, cholesterol, cholesteryl ester, free fatty acids, steroid hormones and a standard clinical blood panel. The fatty acid composition of the plasma lipid fraction was also analyzed. Results indicated that 18 of the captive females and three of the seven wild females were undergoing vitellogenesis, i.e. had elevated plasma estradiol and elevated plasma calcium. Vitellogenic females had higher vitamin E than non-vitellogenic females (77.4 microg/ml vs. 28.6 microg/ml in captive females; 24.0 microg/ml vs. 21 microg/ml in wild females). Plasma retinol was similar in all groups, ranging from 0.5 to 1.4 microg/ml and close to values reported in birds. All lipid fractions, with the exception of cholesteryl ester, were higher in captive alligators than in wild alligators. There were also significant differences in the fatty acid composition of wild and captive alligators. Plasma eicosapentaenoic and docasahexaenoic acid were higher in wild than in captive alligators, whereas linoleic was higher in captive than in wild. PMID- 11207443 TI - Seasonal changes in thermotropic behavior of phosphatidylcholine and phosphatidylethanolamine in different organs of the ascidian Halocynthia aurantium. AB - Differential scanning calorimetry and polarising microscopy were used to investigate the crystal-liquid crystal-isotropic melt phase transitions of phosphatidylcholine (PC), and phosphatidylethanolamine (PE), isolated from muscles, gill pouches, gonads and digestive glands of Halocynthia aurantium, collected in summer and winter. We also analyzed the fatty chain composition of these phospholipids. In summer, the crystalline to liquid crystalline phase transitions of PC and PE from different organs were more co-operative than in winter. Their peak maximum temperatures were close and temperature ranges overlapped for summer samples. Peak maximum temperatures of winter samples decreased sharply, by 18-27 degrees C for PC and by 10-44 degrees C for PE, respectively, depending on the organ. Total heat changes of transitions also decreased. Thermograms were completely located at temperatures below -1.7 degrees C (minimal temperature of seawater in winter). In contrast to summer samples, peak maximum temperatures for PC and PE in winter differed significantly, (by 14 30 degrees C depending on organ), while the temperature ranges of their transitions still showed considerable overlap. Simultaneously, the temperature ranges of the liquid crystalline to isotropic phase transitions decreased. The main reason for changes in thermotropic behavior of phospholipids seems to be the decrease of saturated/unsaturated ratios. The existence of stable and thermoadaptative labile phospholipid pools in the membrane structure is proposed. The relationship of these transitions to low- and high-temperature adaptation is discussed. PMID- 11207444 TI - Chemical characterisation of the oligosaccharides in hooded seal (Cystophora cristata) and Australian fur seal (Arctocephalus pusillus doriferus) milk. AB - Carbohydrates were extracted from hooded seal milk, Crystophora cristata (family Phocidae). Free oligosaccharides were separated by gel filtration and then purified by ion exchange chromatography, gel filtration and preparative thin layer or paper chromatography and their structures determined by 1H-NMR. The hooded seal milk was found to contain inositol and at least nine oligosaccharides, most of which had lacto-N-neotetraose or lacto-N-neohexaose as core units, similar to those in milk of other species of Carnivora such as bears (Ursidae). Their structures were as follows: Gal(beta1-4)Glc (lactose); Fuc(alpha1-2)Gal(beta1-4)Glc (2'-fucosyllactose); Gal(beta1-4)GlcNAc(beta1 3)Gal(beta1-4)Glc (lacto-N-neotetraose); Fuc(alpha1-2)Gal(beta1-4)GlcNAc(beta1 3)Gal(beta1-4)Glc (lacto-N-fucopentaose IV); Gal(beta1-4)GlcNAc(beta1 3)[Gal(beta1-4)GlcNAc(beta1-6)]Gal(1-4)Glc (lacto-N-neohexaose); Fuc(alpha1 2)Gal(beta1-4)GlcNAc(beta1-3)[Gal(beta1-4)GlcNAc(beta1-6)]Gal(beta1-4)Glc (monofucosyl lacto-N-neohexaose a); Gal(beta1-4)GlcNAc(beta1-3)[Fuc(alpha1 2)Gal(beta1-4)GlcNAc(beta1-6)]Gal(beta1-4)Glc (monofucosyl lacto-N-neohexaose b); Fuc(alpha1-2)Gal(beta1-4)GlcNAc(beta1-3)[Fuc(alpha1-2)Gal(beta1-4)GlcNAc(beta1 6)]Gal(beta1-4)Glc (difucosyl lacto-N-neohexaose); Gal(beta1-4)GlcNAc(beta1 3)Gal(beta1-4)GlcNAc(beta1-3)Gal(beta1-4)Glc (para lacto-N-neohexaose); Fuc(alpha1-2)Gal(beta1-4)GlcNAc(beta1-3)Gal(beta1-4)GlcNAc(beta1-3)Gal(beta1 4)Glc (monofucosyl para lacto-N-neohexaose). Milk of the Australian fur seal, Arctophalus pusillus doriferus (family Otariidae) contained inositol but no lactose or free oligosaccharides. These results, therefore, support the hypothesis that the milk of otariids, unlike that of phocids, contains no free reducing saccharides. PMID- 11207445 TI - Isolation and characterization of mitochondrial F(1)-ATPase from crayfish (Orconectes virilis) gills. AB - A soluble F(1)-ATPase was isolated from the mitochondria of crayfish (Orconectes virilis) gill tissue. The maximal mitochondrial disruption rate (95%) was obtained by sonicating for 4 min at pH 8.6. A 15-fold purification was estimated. The properties for both soluble and membrane-bound enzyme were studied. Both enzyme forms were stable at 4 to -70 degrees C when kept in 20% glycerol. Soluble F(1)-ATPase was more stable at room temperature than membrane-bound enzyme. It displayed a narrower pH profile (pK(1) =6.58, pK(2)=7.68) and more acid pH optimum (7.13) than membrane-bound enzyme (pK(1)=6.42, pK(2)=8.55, optimum pH 7.49). The anion-stimulated activities were in the order HCO(3)(-)>SO(4)(2-)>Cl( ). The apparent K(a) values for soluble enzyme were 11.4, 11.2, and 10.9 mM, respectively, but the K(a) of HCO(3)(-) for membrane-bound enzyme (14.9 mM) was higher than for soluble enzyme. Oligomycin and DCCD inhibited membrane-bound F(1) ATPase with I(50) of 18.6 ng/ml and 2.2 microM, respectively, but were ineffective in inhibiting soluble enzyme. Both enzyme forms shared identical sensitivity to DIDS (I(50)=12.5 microM) and vanadate (I(50)=9.0 mM). Soluble ATPase was significantly more sensitive to pCMB (I(50)=0.15 microM) and NO(3)(-) (I(50)=28.6 mM) than membrane-bound enzyme (I(50)=1.04 microM pCMB and 81.5 mM NO(3)(-)). In addition, soluble F(1)-ATPase was slightly more sensitive to azide (I(50)=91.8 microM) and NBD-Cl (I(50)=9.18 microM) than membrane-bound enzyme (I(50)=111.6 microM azide and 12.88 microM NBD-Cl). These data suggest a conformational change transmission between F(0) and F(1) sectors and slight conformational differences between soluble F(1) and membrane-bound F(1). In addition, an unmodified F(0) stabilizes F(1) and decreases F(1) sensitivities to inhibitors and modulators. PMID- 11207446 TI - Kinetic studies on mitochondrial F(1)-ATPase from crayfish (Orconectes virilis) gills. AB - The substrate kinetics and the role of free Mg(2+) and free ATP were studied in membrane-bound F(1)-ATPase from crayfish (Orconectes virilis) gills. It was shown that the MgATP complex was the true substrate for the ATPase activity with a K(m) value of 0.327 mM. In the absence of bicarbonate, the maximum azide-sensitive activities in the presence and absence (<18 microM) of free ATP were 0.878 and 0.520 micromol P(i)/mg protein/min, respectively, while the maximum bicarbonate stimulated activity in absence of free ATP was 1.486 micromol P(i)/mg protein/min. Free ATP was a competitive inhibitor (K(i)=0.77 mM) and free Mg(2+) was a mixed inhibitor (K(i)=0.81 mM, K(i)'=5.89 mM). However, free ATP also acted as an activator. Lineweaver-Burk plots for MgATP hydrolysis at high free Mg(2+) concentrations exhibited an apparent negative cooperativity, which was not the case for high free ATP levels. These results suggest that, although free ATP inhibited the enzyme by binding to catalytic sites, it stimulated ATPase activity by binding to non-catalytic sites and promoted the dissociation of inhibitory MgADP from the catalytic site. PMID- 11207447 TI - Purification and characterization of cathepsin D from herring muscle (Clupea harengus). AB - Cathepsin D was purified and concentrated 469-fold from a homogenate of Clupea harengus muscle. The purified enzyme is a monomer with a molecular weight of 38000-39000. It is inhibited by pepstatin and has optimal activity at pH 2.5 with hemoglobin as the substrate. The isoelectric point is at pH 6.8. Glycosidase treatment and binding to Concanavalin A indicated that the enzyme contains one N linked carbohydrate moiety of the high-mannose type per molecule. The first 21 amino acid residues of the N-terminal showed high similarity to cathepsin D from antarctic icefish liver (Chionodraco hamatus) and trout ovary (Oncorhynchus mykiss). Digestion of the beta-chain of oxidized insulin resulted in preferential cleavage at Leu(15)-Tyr(16), (47%), Tyr(16)-Leu(17) (34%) and Ala(14)-Leu(15) (18%). Incubation with myofibrils from herring muscle at pH 4.23 showed that the enzyme mainly degraded myosin, actin and tropomyosin. PMID- 11207448 TI - Adaptation of tobacco budworm Heliothis virescens to proteinase inhibitors may be mediated by the synthesis of new proteinases. AB - The tobacco budworm Heliothis virescens is adapted to feed on tobacco leaves that have proteinase protein inhibitors (PIs). To study this adaptation, the midgut proteinases of Heliothis virescens larvae reared on artificial PI-free diet and on tobacco leaves were compared using ion exchange chromatography, hydrophobic chromatography, gel filtration and polyacrylamide gel electrophoresis at different conditions. SDS polyacrylamide-gradient gel electrophoresis (SDS-PAGE) and kinetic studies shown that leaf-fed larvae have a chymotrypsin (M(r) 26000) and four trypsins (T1-T4) with the following properties: T1, K(m) 0.3 microM, M(r) 70000; T2, K(m) 0.4 microM, M(r) 67000; T3, K(m) 2.4 microM, M(r) 29000; T4, K(m) 15 microM, M(r) 17000. Diet-fed larvae have a chymotrypsin (M(r) 26000) and a major trypsin (K(m) 2.9 microM, M(r) 29000). Native PAGE at different gel concentrations showed that in these conditions, only T1 and T2 occur in leaf-fed larvae, whereas gel filtration in the absence and presence of SDS revealed that T1 and T2 might arise by polymerization of T3 and T4, respectively. The data suggest that, in the presence of PI-containing food, H. virescens larvae express new trypsin molecules that form oligomers and are apparently less affected by PIs because of tighter binding to the substrate (lower K(m) values) and a putative decreased affinity for PIs. PMID- 11207450 TI - A systematic review of treatments for severe psoriasis. PMID- 11207451 TI - Equity and the economic evaluation of healthcare. PMID- 11207452 TI - A millstone in the uphill battle for credibility. PMID- 11207453 TI - Nutritional strategies for treating chronic fatigue syndrome. PMID- 11207454 TI - Natural agents in the prevention of cancer. Part 1: human chemoprevention trials. AB - Data exist in the scientific literature showing reduction in the risk of tumor occurrence achieved by the use of nutritional and other natural materials. However, many trials that have attempted to prevent cancer occurrence with nutritional supplementation have found no effect or even increased tumor incidence. Several factors appear to be responsible for these disparate data, including the forms of nutrients used and the types of cancer being studied. In addition, combinations of nutrients have often been found to be more effective than single nutrient interventions. Appropriate use of supplemental nutrition, along with attention to pertinent dietary and lifestyle risk factors, comprise for the average person perhaps the best presently available strategy for prevention of the common types of malignancy. PMID- 11207455 TI - The etiologies, pathophysiology, and alternative/complementary treatment of asthma. AB - A chronic inflammatory disorder of the respiratory airways, asthma is characterized by bronchial airway inflammation resulting in increased mucus production and airway hyper-responsiveness. The resultant symptomatology includes episodes of wheezing, coughing, and shortness of breath. Asthma is a multifactorial disease process with genetic, allergic, environmental, infectious, emotional, and nutritional components. The underlying pathophysiology of asthma is airway inflammation. The underlying process driving and maintaining the asthmatic inflammatory process appears to be an abnormal or inadequately regulated CD4+ T-cell immune response. The T-helper 2 (Th2) subset produces cytokines including interleukin-4 (IL-4), IL-5, IL-6, IL-9, IL-10, and IL-13, which stimulate the growth, differentiation, and recruitment of mast cells, basophils, eosinophils, and B-cells, all of which are involved in humoral immunity, inflammation, and the allergic response. In asthma, this arm of the immune response is overactive, while Th1 activity, generally corresponding more to cell-mediated immunity, is dampened. It is not yet known why asthmatics have this out-of-balance immune activity, but genetics, viruses, fungi, heavy metals, nutrition, and pollution all can be contributors. A plant lipid preparation containing sterols and sterolins has been shown to dampen Th2 activity. Antioxidant nutrients, especially vitamins C and E, selenium, and zinc appear to be necessary in asthma treatment. Vitamins B6 and B12 also may be helpful. Omega 3 fatty acids from fish, the flavonoid quercetin, and botanicals Tylophora asthmatica, Boswellia serrata and Petasites hybridus address the inflammatory component. Physical modalities, including yoga, massage, biofeedback, acupuncture, and chiropractic can also be of help. PMID- 11207456 TI - Maitake extracts and their therapeutic potential. AB - Maitake (Grifola frondosa) is the Japanese name for an edible fungus with a large fruiting body characterized by overlapping caps. It is a premier culinary as well as medicinal mushroom. Maitake is increasingly being recognized as a potent source of polysaccharide compounds with dramatic health-promoting potential. The most recent development is the MD-fraction, a proprietary maitake extract its Japanese inventors consider to be a notable advance upon the preceding D fraction. The D-fraction, the MD-fraction, and other extracts, often in combination with whole maitake powder, have shown particular promise as immunomodulating agents, and as an adjunct to cancer and HIV therapy. They may also provide some benefit in the treatment of hyperlipidemia, hypertension, and hepatitis. PMID- 11207457 TI - Can manipulation of the ratios of essential fatty acids slow the rapid rate of postmenopausal bone loss? AB - The rapid rate of postmenopausal bone loss is mediated by the inflammatory cytokines interleukin-1, interleukin-6, and tumor necrosis factor alpha. Dietary supplementation with fish oil, flaxseeds, and flaxseed oil in animals and healthy humans significantly reduces cytokine production while concomitantly increasing calcium absorption, bone calcium, and bone density. Possibilities may exist for the therapeutic use of the omega-3 fatty acids, as supplements or in the diet, to blunt the increase of the inflammatory bone resorbing cytokines produced in the early postmenopausal years, in order to slow the rapid rate of postmenopausal bone loss. Evidence also points to the possible benefit of gamma-linolenic acid in preserving bone density. PMID- 11207458 TI - Taurine - monograph. PMID- 11207459 TI - Idebenone - monograph. PMID- 11207460 TI - Vitamin B6 (pyridoxine and pyridoxal 5'-phosphate) - monograph. PMID- 11207461 TI - How to use evidence-based medicine in anaesthesiology. PMID- 11207462 TI - The assessment of postoperative cognitive function. AB - Postoperative cognitive function (POCD) has been subject to extensive research. In the literature, large differences are apparent in methodology such as the test batteries, the interval between sessions, the endpoints to be analysed, statistical methods, and how neuropsychological deficits are defined. Traditionally, intelligence tests or tests developed for clinical neuropsychology have been used. The tests for detecting POCD should be based on well-described sensitivity and suitability in relation to surgical patients. In tests using scores, floor/ceiling effects may compromise the evaluation if the tests are either too easy or to difficult. Uncontrolled testing facilities and change of test personnel may affect the test performance. Practice effects are pronounced in neuropsychological tests but have generally been ignored. The use of a suitable normative population is essential to allow correction for practice effects and variability between sessions. Missing follow-up may severely compromise valid conclusions since subjects unable or unwilling to be examined are particularly prone to suffer from POCD. In the statistical analysis of the test results, the evaluation should be based on differences between pre- and postoperative performance. Parametric statistical tests are not relevant unless the appropriate Gaussian distributions are present, perhaps after transformation of data. The definition of cognitive dysfunction should be restrictive and the criteria should be fulfilled in only a small proportion of volunteers. In the literature, these requirements often have not been fulfilled. This precludes a reasonable estimation of the incidence of POCD and the conclusions of comparative studies should be interpreted with great caution. In this review article, we present a number of recommendations for the design and execution of studies within this area. In addition, the critical reader may use these recommendations in the evaluation of the literature. PMID- 11207463 TI - Is transient lumbar pain after spinal anaesthesia with lidocaine influenced by early mobilisation? AB - BACKGROUND: The aetiology of transient lumbar pain (TLP) after spinal anaesthesia has generated much interest. Many theories have been discussed. Early ambulation has been suggested as one plausible theory for developing TLP. METHODS: A total of 107 patients scheduled for inguinal hernial repair under spinal anaesthesia (20 mg/ml hyperbaric lidocaine) were randomised to either early or late ambulation: the early ambulation (group A), as early as possible after total regression of spinal block or the late mobilisation (group B) bedridden for more than 12 h. The clinical course and duration of operation were monitored. Assessments 4, 8 and 12 h after spinal anaesthesia were performed with respect to wound pain, nausea, tiredness and eventual symptoms of TLP were recorded. The patients also kept a diary about any symptoms once daily day 1-3 at home. A telephone follow-up was performed at day 5-7. RESULTS: Our results showed an incidence of TLP of 23% in all patients. No difference was recorded between early and late mobilisation patients, 12 and 13 patients, respectively. CONCLUSION: Early ambulation does not seem to increase the risk of developing TLP. PMID- 11207465 TI - Risk factors for preoperative anxiety in adults. AB - BACKGROUND: Patients who undergo surgery experience acute psychological distress in the preoperative period. The objective of this study was to identify and quantify the effect of risk factors for preoperative anxiety in adults. METHODS: A cross-sectional study was performed with 592 inpatients scheduled for elective surgery. Age ranged from 18 to 60 years (ASA physical status I-III). Demographic information was collected using a structured questionnaire. The measuring instruments were a visual analog scale, the State-Trait Anxiety Inventory; the Montgomery-Asberg Depression Rating Scale, the WHO Self-Reporting Questionnaire 20, and the future self-perception questionnaire. Multivariate conditional regression modeling was used to control confounding factors and to determine independent predictors of preoperative anxiety, taking into account the hierarchical relationship between risk factors. RESULTS: High preoperative anxiety was associated with history of cancer (odds ratio (OR)=2.26) and smoking (OR=7.47), psychiatric disorders (OR=5.93), negative future perception (OR= 2.30), moderate to intense depressive symptoms (3.22), high trait-anxiety (3.83), moderate to intense pain (2.12), medium surgery (OR=1.52), female gender (OR=2.0), ASA category III (OR=3.41), up to 12 years of education (OR=1.36), and more than 12 years of education (OR=1.68). Previous surgery (OR= 0.61) was associated with lower risk for preoperative state-anxiety. CONCLUSIONS: History of cancer and smoking, psychiatric disorders, negative future perception, moderate to intense depressive symptoms, high trait-anxiety, moderate to intense pain, medium surgery, female gender, ASA category III, up to 12 years of education and more than 12 years of education constituted independent risk factors for preoperative state-anxiety. Previous surgery reduced the risk for preoperative anxiety. PMID- 11207464 TI - Unintentional hypotension from lidocaine infiltration during orthognathic surgery and general anaesthesia. AB - BACKGROUND: A probable causal relationship between submucosal infiltration of lidocaine, with adrenaline 12.5 microg x mL(-1), and untoward arterial hypotension during general anaesthesia for orthognathic surgery was investigated in two parts. METHODS: The first part of the study was open and non-randomised. The patients served as their own controls, receiving 5.4 mL saline/adrenaline before mandibular or maxillary surgery on the first side of the jaw and 5.4 mL lidocaine (2%)/adrenaline on the other side a minimum of 40 min later. Nine patients received in total 11 pairs of injections of the study drugs. In Part Two, 50 mg or 100 mg of lidocaine with adrenaline was infiltrated in an observer blinded and randomised order in either side of the jaw in another 13 patients. RESULTS: A significant and dose-dependent blood pressure decrease was observed after infiltration of lidocaine/adrenaline, but not after saline/adrenaline. The heart rate increased significantly after both types of injections, most pronounced after saline/adrenaline. Mean arterial blood pressure decreased on average 11% and 23% with lidocaine 50 mg and 100 mg, respectively (P<0.05, ANOVA). CONCLUSION: Lidocaine induced dose-dependent arterial hypotension when combined with a defined level of general anaesthesia. The causative mechanism is unclear. PMID- 11207466 TI - Reduced isoflurane consumption with bispectral index monitoring. AB - BACKGROUND: Bispectral index (BIS) monitoring has been found to decrease the requirements for propofol, sevoflurane and desflurane and to improve recovery. We wanted to assess the effect of BIS monitoring on intraoperative isoflurane utilisation, and the early recovery profile. METHODS: Eighty patients undergoing various surgical procedures were studied. In the first phase of the study, patients were anaesthetised without the use of BIS, the anaesthetists being blinded to the BIS readings, and isoflurane being administered according to standard clinical practice (control group). In a second phase, isoflurane was titrated to maintain a BIS value between 40 and 60 during surgery, and then 60-70 during 15 min prior to the end of surgery (BIS group). Isoflurane consumption was measured. Recovery times and the time to achieve a modified Aldrete score of 9 were recorded. RESULTS: Despite similar mean BIS levels during maintenance of anaesthesia, the cumulative time spent with BIS values between 40 and 60 during maintenance of anaesthesia was significantly longer in the BIS group as compared with the control group (P<0.001). The isoflurane usage in the BIS group was 12 25% lower than in the control group (P<0.05). The time to awakening and extubation were comparable in the two groups. Although the patients were less sedated (P<0.01) during the three postoperative hours in the BIS (vs. control) group, no significant differences were observed in the time to obtain an Aldrete score of 9. CONCLUSION: The addition of BIS to standard monitoring decreases isoflurane consumption. However, we found only a small advantage in using BIS with respect to recovery from isoflurane anaesthesia. PMID- 11207467 TI - Management of anaphylactic shock evaluated using a full-scale anaesthesia simulator. AB - BACKGROUND: The diagnosis of an anaphylactic reaction during anaesthesia is not the first consideration for the anaesthetist and might be missed. The aim of this study was to describe anaesthetists' management of an anaphylactic reaction concerning diagnosing, treatment and application of anaesthesia crisis resource management (ACRM) in a full-scale anaesthesia simulator. METHODS: Forty-two anaesthetists in teams of two attended training sessions with a critical incident of anaphylactic shock in a full-scale simulator. Trained observers from the study group evaluated the medical treatment according to a treatment sequence developed from the literature and graded the ACRM performance on a five-point scale where 1 is bad and 5 is best. RESULTS: None of the teams made the correct diagnosis within 10 min and treatment according to the treatment sequence was not initiated. Only 6/21 teams considered the right diagnosis but first after hints from the instructor 15 min after the start of the incident. Evaluation of the use of the total ACRM concept (that is the use of all of the ACRM expressions seen in a total connection: called general impression) gave a median value of 2.0 with a range of (1-3). CONCLUSION: Anaphylactic shock was difficult to diagnose and no structured plans were used for the treatment in the simulated incident in this study. PMID- 11207468 TI - Recovery profile and side effects of remifentanil-based anaesthesia with desflurane or propofol for laparoscopic cholecystectomy. AB - BACKGROUND: Nitrous oxide (N2O) has been suggested to contribute to bowel distension, resulting in worsened operating conditions for laparoscopic surgery, and to increase incidence of postoperative nausea and vomiting. Therefore, our objective was to assess the feasibility of two remifentanil-based anaesthetic regimens free from N2O with special regard to recovery profile, postoperative analgesic demand and side effects in patients undergoing laparoscopic cholecystectomy. METHODS: Fifty patients (ASA I-II, 23-65 yr) were randomly assigned to receive remifentanil-based anaesthesia in conjunction with propofol (group R/P) or desflurane (group R/D). After standardised induction of anaesthesia, analgesia was continued with remifentanil in all patients. For maintenance of hypnosis, propofol or desflurane were used in concentrations to ensure loss of consciousness, lack of awareness, and maintenance of heart rate and blood pressure within +/- 25% of initial values. At the end of surgery all anaesthetics were discontinued without tapering and early emergence and recovery were recorded. Pain scores were assessed by using a visual analogue scale. Patient-controlled analgesia with i.v. piritramide was used for treatment of postoperative pain and recorded for 90 min in the postanaesthesia care unit (PACU). In addition, side effects were noted. RESULTS: Early emergence from anaesthesia did not differ between the groups. In group R/P, time to eye opening, spontaneous respiration and extubation was 4.4 +/- 2.9 min, 5.2 +/- 3.4 min and 5.5 +/- 3.3 min respectively, compared with 4.7 +/- 2.7 min, 5.3 +/- 2.4 min and 5.7 +/- 2.5 min in group R/D. While pain scores did not differ between both groups on admission to the PACU, patients receiving desflurane required more i.v. piritramide as compared to those receiving propofol, 22.0 +/- 6.5 mg and 17.9 +/- 7.0 mg, respectively (P<0.05). Nausea was less frequent after propofol (16% vs. 48%, P<0.05). CONCLUSION: In patients undergoing laparoscopic cholecystectomy, remifentanil-based anaesthetic regimens in conjunction with propofol or desflurane are suitable and allow for rapid recovery from anaesthesia. However, the use of propofol results in less postoperative analgesic consumption and nausea as compared to desflurane. PMID- 11207469 TI - A survey of tracheal intubation difficulty in the operating room: a prospective observational study. AB - BACKGROUND: The purpose of this study is to describe all degrees of endotracheal intubation difficulty among patients attended by eight anesthesiologists during routine surgery over a six-month period. Airway characteristics were routinely assessed preoperatively, according to the anesthesiologists' usual practice. METHODS: Difficult tracheal intubation was evaluated by the Intubation Difficulty Scale (IDS), a quantitative score based on seven variables. An IDS value of 0 is consistent with a procedure without difficulty, and an IDS > 5 with a procedure involving moderate to major difficulty. RESULTS: For 1171 patients undergoing tracheal intubation, IDS was 0 in 55%, and greater than 5 in 8% of cases. External laryngeal pressure, repositioning the patient and added use of a stylet were the most frequent methods chosen to facilitate tracheal intubation. CONCLUSION: There was a high incidence (37%) of minor difficulties encountered during routine surgery. PMID- 11207470 TI - Postoperative tracheal extubation after orthotopic liver transplantation. AB - BACKGROUND: The duration of postoperative mechanical ventilation and its influence on pulmonary function in liver transplant recipients is still debated controversially. METHODS: We retrospectively analyzed the incidence of immediate tracheal extubation, prolonged mechanical ventilation (>24 h following surgery), and episodes of reintubation in 546 patients who underwent orthotopic liver transplantation (OLT) at our institution. RESULTS: Immediate tracheal extubation in the operating theater was achieved in 18.7% of patients, and prolonged mechanical ventilation was required by 11.2% of patients. In these, median time of extubation was 49.5 h, whereas the remaining 70.1% of patients required ventilation support for a median 5 h after OLT. As risk factors for prolonged mechanical ventilation we identified the indications of acute liver failure and retransplantation, as well as factors such as mechanical ventilation prior to OLT, massive intraoperative bleeding, and severe reperfusion injury of the liver graft. The incidence of reintubation was 8.8% in patients who were immediately extubated following surgery, and 13.1% in patients who underwent extubation within 24 h. The incidence was significantly increased in patients requiring prolonged mechanical ventilation (36.1%). CONCLUSIONS: Immediate tracheal extubation was safe and well tolerated. The incidence of reintubation was not increased when compared to patients in whom extubation succeeded later. However, special attention should be given to transplant recipients presenting in reduced clinical condition at the time of OLT, undergoing complicated surgery, or receiving liver allografts with severe reperfusion injury because of an increased risk for prolonged mechanical ventilation. PMID- 11207471 TI - Airway pressure release ventilation and prone positioning in severe acute respiratory distress syndrome. AB - BACKGROUND: Implementation of lung protective strategy in the treatment of severe Acute Respiratory Distress Syndrome (ARDS) has been reported to be associated with improved outcome. To fulfil this approach, sedation, neuromuscular blocking agents and full mechanical ventilatory support are often used in critical failure of gas exchange. CASE REPORT: We present a patient who developed multiple organ failure, including severe ARDS, after severe skin injuries and septic shock. Ventilatory strategy consisted of lung protective approach, permissive hypercapnia and prone positioning. Airway pressure release ventilation (APRV) with the patient's superimposed spontaneous breathing was implemented and maintained, also during prone episodes. Improvement of gas exhange occurred after application of combined use of APRV and prone positioning. CONCLUSION: APRV and maintenance of patients' spontaneous ventilation is feasible during prone positioning, and this approach may have beneficial synergistic effects on gas exhange in patients with severe acute lung injury. PMID- 11207472 TI - Postoperative intensive care admittance: the role of tobacco smoking. AB - BACKGROUND: Smokers have been shown to have increased risk of intraoperative pulmonary complications and of a wide range of postoperative complications, but an increased risk of postoperative intensive care admittance has not yet been described. The aim of this study was to estimate the risk of pulmonary complications and postoperative intensive care admittance in smokers and non smokers in a general and orthopaedic surgical population. METHODS: A total of 4725 surgical patients were assessed. The following information was noted: age, sex and smoking status, history of heart and lung disease, ASA classification, type of anaesthesia, intensive care admittance and postoperative pulmonary or cardiovascular complications. A logistic regression model was used to determine the probability of intensive care admittance and pulmonary complications as a function of smoking status, age, and chronic heart and lung disease. RESULTS: Of the patients, 39.9% were smokers, 45.5% were non-smokers and in 14.6% of the cases smoking status was unspecified. Postoperative intensive care admittance and pulmonary complications were found in 2.0% and 4.3% of the patients, respectively. Non-smokers were more often female (P<0.01), and smokers had a higher incidence of emergency surgical procedures (P<0.05). When applying multiple regression analysis, we found that smoking, age >65 years, and a history of chronic lung disease increased the risk of unplanned intensive care admittance (odds ratio 1.55, 12.52 and 2.73). CONCLUSION: Our results indicate a relationship between a history of tobacco smoking and postoperative intensive care admittance. PMID- 11207473 TI - Modelling of hypoxaemia after gynaecological laparotomy. AB - BACKGROUND: Late postoperative arterial hypoxaemia is common after major surgery, and may contribute to cardiovascular, cerebral or wound complications. This study investigates the time course of hypoxaemia following gynaecological laparotomy, and estimates parameters of mathematical models of pulmonary gas exchange to describe hypoxaemia. METHODS: Twelve patients were studied on four occasions; preoperatively, 2, 8 and 48 h after surgery. On each occasion inspired oxygen fraction (FIO2) was varied, changing end-expired oxygen fraction (FEO2) to achieve arterial oxygen saturations (SaO2) ranging from 90% to 100%. Measurements of ventilation and blood gases were taken. Oxygenation was characterized plotting FEO2 against SaO2. The shape and position of the FEO2/SaO2 curve was described using two mathematical models including parameters describing gas exchange: either shunt and resistance to oxygen diffusion (Rdiff); or shunt and asymmetry of ventilation-perfusion (fA2). RESULTS: Two hours after surgery SaO2 was reduced from 97.5%+/-1.2% (mean+/-SD) to 93.8%+/-2.7% (mean+/-SD) (P<0.001). Values of shunt, Rdiff and fA2 were significantly changed at 2 and 8 h postoperatively. Forty-eight hours postoperatively Rdiff and fA2 were still significantly changed. CONCLUSION: Oxygenation in 12 patients preoperatively, 2, 8 and 48 h after gynaecological laparotomy is described. Two patients were hypoxaemic (SaO2 <92%) 48 h postoperatively. When two different models of oxygen transport are fitted to patient data, high values of Rdiff or low values of fA2 describe the right shift in the FEO2/SaO2 curve seen in patients with oxygenation problems. These models fit patient data identically, and may be useful in quantifying postoperative hypoxaemia. PMID- 11207474 TI - End-tidal to arterial oxygen tension difference as an oxygenation index. AB - BACKGROUND: "Ideal" alveolar oxygen tension (PAO2) is a calculated entity and the alveolar-arterial oxygen tension difference (PA-aO2) is used to evaluate gas exchange function of the lungs. Accurate calculations of PAO2 necessitate measurements of the respiratory exchange ratio (RER), which is less frequently done, and most often approximations are made. The measured end-tidal oxygen tension (PETO2) is a reflection of the alveolar oxygen tension. The aim was to study the relationship between PAO2 and PETO2, and to see whether the end-tidal to arterial oxygen tension difference (PET-aO2) could give the same information about lung function as PA-aO2. METHODS: Twenty patients admitted for cardio pulmonary exercise tests were studied. They bicycled for 4 min at each work load until maximum work load was reached. Arterial blood gases were analysed before, after 4 min at each work load, at maximum work load and after 2 min of recovery. A metabolic computer measured mixed expired gas concentrations. End-tidal gas concentrations were measured with a side stream gas analyser. RESULTS: We measured major increases in oxygen uptake, carbon dioxide elimination and RER. PAO2 and PETO2 increased at maximum exercise and during recovery. PAO2 and PETO2 were closely correlated during the study, through great changes in oxygen uptake and RER (r=0.88). When correction was made for wet gas the median difference was 0.12 kPa. CONCLUSIONS: At ambient air (FIO2=0.21), PET-aO2 as a respiratory index may give equivalent information to PA-aO2, without the need for measurements of mixed expired gas tensions or the hazard of an assumed RER. PMID- 11207475 TI - Early detection of increased tumour necrosis factor alpha (TNFalpha) and soluble TNF receptor protein plasma levels after trauma reveals associations with the clinical course. AB - BACKGROUND: The inflammatory response after trauma includes tumour necrosis factor alpha (TNFalpha) as pro-inflammatory cytokine. Furthermore, both soluble TNF receptor proteins (sTNF-R1 and sTNF-R2) were described to influence the post traumatic inflammatory response and organ dysfunction. METHOD: From 47 trauma patients, blood samples were obtained at the scene of accident, at hospital admission, after 4 h, 12 h, and 24 h, and daily until day 6. Plasma levels of TNFalpha, sTNFR1 and sTNF-R2 were measured by enzyme immunoassay (EIA) and analysed comparing clinical parameters such as injury scores (ISS, AIS), development of multiple organ dysfunction syndrome (MODS) and/or systemic inflammatory response syndrome (SIRS), and outcome. RESULTS: Significant changes were observed in a time-dependent manner: TNFalpha and soluble TNF receptor levels were elevated compared to values of healthy persons. At 4 h after trauma, TNFalpha and sTNF-R2 showed an increase from initial values, which continued during the entire observation period. Severe trauma led to enhanced sTNF-R1 levels on scene and on hospital admission. Development of SIRS along with elevated sTNF-R1 began on scene and was present on admission, with increased sTNF R2 from day 1 to day 4. MODS (until day 6) was preceded by increased sTNF-R2 levels on admission and up to 4 h after trauma. Outcome was associated neither with TNFalpha nor with soluble TNF receptor levels. CONCLUSION: Thus, in trauma patients, early post-traumatic MODS and SIRS coincide with increased levels of TNFalpha and TNF receptor proteins, revealing different, time-dependent changes. Hence, detection of TNFalpha and soluble TNF receptor proteins after trauma should pay regard to the time point of sampling. PMID- 11207476 TI - Blood viscosity, hemodynamics and vascular hindrance in a rat model of acute controlled bleeding and volume restitution with blood or Haemaccel. AB - BACKGROUND: Hemorrhage and volume restitution with commercially available solutions is followed by reduced blood viscosity. Consequent hemodynamic changes may arise not only from the reduced viscosity itself but also from changes in vascular geometry induced by autoregulation processes. Vascular hindrance reflects the contribution of vascular geometry to flow. Our aim was to explore the possible effects of blood volume restitution with Haemaccel or blood, on regional blood flow and vascular geometry. METHODS: Under ketamine anesthesia, blood was withdrawn at a rate of 0.3 ml/min for 15 min followed by 15 min of stabilization. The shed blood or Haemaccel was infused at the same rate and volume as used for withdrawal. Hemodynamic measurements were performed using radioactive microspheres. Blood viscosity was measured with an Ostwald viscometer. Vascular hindrance was calculated as the resistance/viscosity ratio. RESULTS: Volume replacement with Haemaccel (n=10), compared to blood (n=10), was followed by increased cardiac output and portal venous inflow (37.1 +/- 9.0 and 3.1 +/- 0.5 vs 25.9 +/- 6.8 and 2.2 +/- 0.9 ml x min(-1) x 100 g bw(-1), respectively; P<0.05), decreased viscosity (2.8 +/- 1.3 vs 3.7 +/- 1.3, respectively; P<0.01) and decreased peripheral and splanchnic arteriolar resistance (3.8 +/- 1.1 and 40.9 +/- 7.6 vs 5.2 +/- 1.7 and 61.1 +/- 29.5 mmHg x ml(-1) x min x 100 g bw, respectively; P<0.05). No significant differences between the groups were observed in vascular hindrance and cardiac output distribution. CONCLUSION: Volume replacement with Haemaccel, compared to blood, induced increase in systemic and splanchnic blood flows, reflecting mainly changes in viscosity and not in blood vessel geometry. These results suggest no significant difference in overall activation of autoregulation process between volume restitution with blood or Haemaccel. PMID- 11207477 TI - The effect of chronic cocaine administration on hemodynamic stability and neurohumoral mediators during isoflurane anesthesia and shock in rats. AB - BACKGROUND: The aim of this investigation was to determine whether chronic cocaine administration altered endogenous vasoconstrictor secretion in response to hypotension from isoflurane anesthesia and blood loss in rats. METHODS: Rats received continuous intravenous infusions of saline (n=11), or cocaine 6 mg kg( 1) d(-1) (n=13) or 18 mg kg(-1) d(-1) (n=12) for 13 days. On day 14, rats were anesthetized with intraperitoneal ketamine and xylazine and a femoral artery catheter and a tracheotomy performed to allow lung ventilation (PaCO2, 30-40 mmHg). After baseline parameters were noted, isoflurane was introduced to end tidal concentrations of 0.7% for 10 min (1/2 MAC), 1.4% for 10 min (MAC) and again 0.7% for 10 min (1/2 MAC-2) when 5 ml of blood was withdrawn (SHOCK). Blood samples were drawn to assess arterial blood gas indices at various time points as well as plasma epinephrine, angiotensin II and vasopressin at MAC, 1/2 MAC-2 and SHOCK. RESULTS: Rats administered cocaine had higher oxygen extraction, required higher minute ventilation and had lower PaO2 values than rats administered saline despite similar body temperatures and hematocrits. Isoflurane administration resulted in significant dose dependent but similar blood pressure decreases in all study groups. Plasma epinephrine, angiotensin II and vasopressin concentrations were not different in saline or cocaine treated animals at any time point. CONCLUSION: These data suggest that chronic cocaine treatment in rats does not impair endogenous vasoconstrictor secretion nor alter the heart rate and blood pressure response to isoflurane and blood loss. PMID- 11207478 TI - Influence of colloid fluids on polymorphonuclear granulocyte function in vivo. AB - BACKGROUND: Granulocytes have a role in the immediate immune response. In a previous investigation we could demonstrate in vitro a moderate increase of the complement receptors CR1 (CD35) and CR3 (CD11b/CD18) on the surface of polymorphonuclear neutrophils (PMN) after incubation of whole blood with colloids. To elucidate the clinical significance, we investigated if these changes were also present in vivo. METHODS: The study was performed prior to anaesthesia for orthopaedic surgery. A total of 60 ASA-I patients was evaluated. Patients received in a randomised manner 7 mL/kg of the following solutions: human albumin 5% (HA), gelatine 4% (GEL), hydroxyethylstarch solution 6% with MW 200,000 Da, degree of substitution 0.5 (HES), or Ringer's solution. Prior to the infusion, at the end (30 min) and again 30 min later, blood samples were taken. Blood was incubated with fluorescein-conjugated monoclonal antibodies (CD11b, CD16, CD35, CD62L) and analysed with flow cytometry. RESULTS: HA, GEL, HES, and Ringer's solution failed to induce significant differences in the expression of complement receptors CR1 (CD35) and CR3 (CD11b/CD18), Fc gamma receptor IIIb (CD16), and of L-selectin (CD62L) receptor on the surface of PMN. CONCLUSIONS: Application of colloids like HA, GEL, or HES in moderate amounts shows no short term effect on adhesion or activation molecules on granulocytes. However, in high doses, infused in situations such as multiple trauma and sepsis, the consequences on the function of PMN may be speculative and require further investigations. PMID- 11207479 TI - Increased blood-brain barrier permeability of morphine in a patient with severe brain lesions as determined by microdialysis. AB - Intracerebral microdialysis was utilised to obtain information regarding how morphine is transported across the blood-brain barrier (BBB). In a patient with a severe brain injury, we measured simultaneously unbound extracellular fluid (ECF) concentrations of morphine in human brain and in subcutaneous fat tissue, which were compared to morphine levels in arterial blood. This report shows an increase in morphine levels near the trauma site in the brain compared to uninjured brain tissue. The half-life of morphine in uninjured and injured brain tissue of 178 min and 169 min, respectively, were comparable but were longer than in blood (64 min) and adipose tissue (63 min). This indicates that morphine is retained in brain tissue for a longer time than what could be expected from the blood concentration-time profile. These results show the potential of the microdialysis technique in providing new information regarding the pharmacokinetics of drug in the human brain close to the trauma site and in macroscopically intact tissue. PMID- 11207480 TI - Life-threatening upper airway obstruction in a child caused by retropharyngeal emphysema. AB - A 2 1/2-year-old boy with acute obstructive lung disease from adenovirus infection developed cough-induced paroxysms of intense dyspnoea leading to respiratory failure. Chest x-ray and fluoroscopy demonstrated retropharyngeal air occluding the airway. The clinical management of this and similar air-leak problems is discussed. PMID- 11207481 TI - Reversible increase in QT dispersion during carbon monoxide poisoning. AB - Increased QT dispersion is a marker for cardiac morbidity and mortality. Carbon monoxide (CO) is a potent myocardial toxin and this report describes the change in QT dispersion during intensive care therapy for severe CO poisoning. PMID- 11207482 TI - Vaginal term breech delivery--a time for reappraisal? PMID- 11207483 TI - Oocyte donation in infertility treatment--a review. PMID- 11207484 TI - Induction of endometriosis in the mouse inhibits spleen leukocyte function. AB - BACKGROUND: It is still unclear whether the immunologic perturbation observed in women with endometriosis represents an intrinsic defect of the immune system or it is consequent to the presence of endometrium in ectopic sites. The present study was aimed to evaluate the immunoregulatory properties of ectopic endometrial implants in a model of experimental endometriosis in mice. METHODS: Endometriosis was induced in n=10 mice by inoculating endometrial fragments obtained from syngenic donor mice into the peritoneal space. Twelve mice were similarly treated but were not inoculated with endometrium and were used as control mice. At an explorative laparotomy performed in all the animals after three weeks, the extent of peritoneal lesions, when present, was evaluated by weight assessment and surface area measurement. In both mice that were inoculated with endometrium and control animals, spleens were removed. The effect of endometriosis induction on concanavalin A-induced spleenocyte proliferation was investigated. RESULTS: A significant inhibition of spleenocyte growth was demonstrated in mice in which endometriosis was induced (36156+/-3061 cpm) compared to control animals (47172+/-3210 cpm; p<0.05). Moreover, a significant inverse correlation was found between spleenocyte proliferation and weight and surface area of the peritoneal endometriotic lesions (r=0.76; p<0.02 and r=0.75; p<0.02, respectively). CONCLUSION: These findings suggest that the presence of ectopic endometrial implants within the peritoneal cavity leads to substantial changes of the immune response in vivo. These changes may have significant implications for the understanding of the etiopathogenesis of endometriosis. PMID- 11207485 TI - Child births in a modified midwife managed unit: selection and transfer according to intended place of delivery. AB - BACKGROUND: As small obstetrical departments may not be able to give second-level perinatal care, the delivery unit at Lofoten hospital was for the years 1997-98 reorganized to a modified midwife managed unit. Women at low obstetrical risk were delivered at this unit and women at high risk were referred to the central hospital. We assessed the effectiveness of the risk selection. MATERIAL AND METHODS: The study was a prospective, pragmatic, population-based trial. Desired outcome was defined as a non-operative delivery at 35-42 weeks gestational age giving an infant not needing resuscitation. Intermediate outcomes: Operative deliveries, infants transferred to neonatal intensive care unit and infants diverging from normal. The intended place of delivery was ultimately decided at admittance to the midwife managed unit. RESULTS: Of the 628 women in study 435 (69.3%) gave birth at the midwife managed unit, 152 (24.2%) were selected to be delivered at the central hospital and 41 (6.5%) were transferred to the central hospital after admittance to the midwife managed unit. Desired outcome was recorded in 94% of the deliveries at the midwife managed unit as compared to 50.3% at the central hospital. Women who intended to be delivered at the midwife managed unit, needed fewer operative deliveries and relatively few infants were transferred to the neonatal intensive care unit or diverged from normal. CONCLUSIONS: As nearly 70% of the births occurred at the midwife managed unit and 94% of these deliveries had a desired outcome, this indicates an effective selection process. This model might be an alternative to centralization of births in sparsely population areas. PMID- 11207486 TI - Symptoms across pregnancy in relation to psychosocial and biomedical factors. AB - BACKGROUND: There is current interest in symptoms during pregnancy, but yet little is known about their prevalence and how often they are experienced across pregnancy. The reasons why some women experience more symptoms or experience them more often than others has received limited research attention. OBJECTIVE: To document the prevalence and frequency of 27 pregnancy symptoms and to systematically investigate, cross-sectionally and prospectively, the effect of psychosocial factors on the prevalence and frequency of these symptoms, while controlling for biomedical factors. METHODS: Four hundred and seventy-six nulliparous Scandinavian women who attended routine prenatal care in Uppsala county, Sweden, were studied six times during pregnancy (gestational weeks 10, 12, 20, 28, 32, and 36). RESULTS: The prevalence of symptoms was high, but only a smaller portion of these symptoms were experienced frequently. Psychological stress particularly contributed to the prevalence and frequency of concurrent symptoms and predicted symptoms up to 16 weeks later, independent of medical risk, smoking, and weight gain. CONCLUSIONS: Prevalence rates may be inflated, because many symptoms were experienced only 'occasionally' during each of the 4 week periods we sampled. By examining how frequently symptoms were experienced, we gained an indication of which symptoms are more likely to be bothersome or intrude upon daily activities. Psychosocial variables accounted for individual differences in symptom reports after taking biomedical factors into account. Attention to psychosocial variables in future studies will aid in our understanding of the etiology of pregnancy symptoms. PMID- 11207487 TI - Prenatal diagnosis of six major cardiac malformations in Europe--a population based study. AB - AIM: To present data on prenatal diagnosis of six major cardiac malformations in low-risk European populations. METHODS: Data from 12 Eurocat registries on congenital malformations. All registries have multiple sources of information and use the same methods of data collection and coding. The six cardiac malformations included were hypoplastic left heart, tricuspid atresia, single ventricle, Tetralogy of Fallot, transposition of great arteries and common A-V-canal. RESULTS: There were significant differences in the proportion of cases diagnosed prenatally, with the highest detection rate in France (91% for single ventricle in Paris) and the lowest detection rate in countries without prenatal ultrasound screening (no cases diagnosed prenatally in the Danish registry area). Prenatal detection rate was significantly higher for the three malformations affecting the size of the ventricles (hypoplastic left heart, tricuspid atresia, single ventricle) compared to the other three malformations (46% versus 24%, p<0.001). Time of diagnosis was late, with only one third diagnosed before 24 weeks of gestation. The risk of fetal death seems to be low. CONCLUSION: There are significant regional differences in prenatal detection rate of major cardiac malformations in Europe. PMID- 11207488 TI - Third and fourth degree perineal tears. Predictor factors in a referral hospital. AB - BACKGROUND: Tears of the anal sphincter are a feared complication of vaginal delivery, as many as 50% of these patients experience incontinence as an after effect. Identifying significant predictor factors leading to third or fourth degree perineal tears during vaginal delivery was the objective of this study. METHODS: During a two-year period (1995-1996), a third or fourth degree perineal rupture occurred in 214 women (3.7%) after vaginal delivery. Data from these deliveries were collected and compared to data from deliveries without anal sphincter tears in order to identify risk factors. A stepwise logistic regression model was used for the analysis. RESULTS: Independent risk factors of significance were vaginal nulliparity, a squatting position on a delivery chair, maternal age exceeding 35 years, baby's birth weight over 4000 g, vacuum extraction (both outlet and mid release), median episiotomy, oxytocin augmentation and birthing between 3 a.m. and 6 a.m. CONCLUSIONS: This study identified several factors associated with anal sphincter tears. Median episiotomy should be avoided. Delivery, while squatting on a low chair, should be used with caution. A woman with one or more risk factors requires caution by birth attendants during delivery. Gynecologists should consider the option of cesarean section instead of vacuum extraction, especially when mid release is needed in the presence of macrosomia. A continuous audit regarding instrumental delivery technique is necessary. PMID- 11207489 TI - Maternal risk factors for cause-specific stillbirth and neonatal death. AB - BACKGROUND: To study specific effects of four maternal risk factors: age, parity, educational level, smoking, for specific causes of stillbirth and neonatal death according to a previously described hierarchic classification. METHODS: The study is based on 9,785 stillbirths or neonatal deaths among infants born in Sweden, 1983-1995 (n=1,412,754) and identified with various Swedish health registers. Statistical analysis is performed using Mantel-Haenszel analysis. RESULTS: Some risk factors, known from the literature, were confirmed and could be quantified. In addition, high parity was shown to increase the risk for death associated with multiple births (OR=2.49, 95% CI 2.07-3.01) and low educational level seems to be protective for such death (OR=0.75, 95% CI 0.60-0.93). If the infant is SGA, the risk for death is higher at high than at low parity (1.70, 95% CI 1.19-2.43, and 1.0, 95% CI 1.06-1.15, respectively). Maternal smoking seems to aggravate the placental abruption because the death risk in the presence of abruption increases when the mother smoked (OR = 1.74, 95% CI 45-2.08). CONCLUSIONS: The study shows that the groups of the classification system used (NICE) differ in their association with known risk factors for stillbirth and neonatal deaths and an analysis based on specific causes of death can therefore unravel risk factors hidden when total mortality is used. The computerized method of classification and the cause-of-death classification developed by us is clearly useful for such analyses which requires large materials. PMID- 11207490 TI - A randomized, controlled trial comparing effect of oral misoprostol and intravenous syntocinon on intra-operative blood loss during cesarean section. AB - BACKGROUND: Oxytocics are routinely used in an attempt to prevent excessive blood loss during cesarean section. Misoprostol, a potent uterotonic agent, has been reported to be useful in the prevention and treatment of postpartum hemorrhage by several investigators but its use during cesarean section has not been described. The objective of this study was to randomly compare the effectiveness of oral misoprostol with intravenous syntocinon on blood loss during elective cesarean sections under regional anesthesia. METHODS: Sixty pregnant women were randomized either to receive misoprostol 400 micrograms orally or syntocinon 10 IU intravenously during cesarean section. The primary outcome measure was intra operative blood loss as estimated by physicians, and by values of preoperative and postoperative hemoglobin concentration and hematocrit. Demographic characteristics of the subjects and outcomes were compared using chi-square test for categorical and two-sample t-test for continuous data. RESULTS: Baseline characteristics in terms of age, body weight, parity, gestational age and indications for cesarean section were similar in both groups. The estimated blood loss was 545 ml (CI 476-614) in misoprostol group and 533 ml (CI 427-639) in syntocinon group (p = 0.85). Differences in preoperative and postoperative hemoglobin and hematocrit values were also similar in both groups. Two women in the misoprostol group and three in the syntocinon group (p=0.64) required additional oxytocics. One patient in each group required blood transfusion. No serious side effects were noted in either group. CONCLUSION: Oral misoprostol appears to be safe and as effective as intravenous syntocinon in reduction of intra-operative blood loss during elective cesarean section under regional anesthesia and merits further investigation. PMID- 11207491 TI - Prevalence of depressive symptoms in late pregnancy and postpartum. AB - BACKGROUND: Postnatal depression refers to a non-psychotic depressive episode that begins in or extends into the postpartum period. The aims of this study were to examine the prevalence of depressive symptoms in a pregnant and later postnatal population, to determine the natural course of these symptoms and whether there is an association between antenatal and postnatal depressive symptomatology. METHODS: A longitudinal study with a total population of 1,558 consecutively registered pregnant women in the southeast region of Sweden. Presence of depressive symptoms was measured with the Edinburgh Postnatal Depression Scale on four occasions namely in gestational week 35-36, in the maternity ward, 6-8 weeks and 6 months postpartum. RESULTS: The prevalence of depressive symptoms during late pregnancy was 17%; in the maternity ward 18%; 6-8 weeks postnatally 13%; and 6 months postnatally, 13%. A correlation between antenatal and postnatal depressive symptoms was found (r=0.50, p<0.0001). CONCLUSION: Detection of women at risk for developing postnatal depressive symptoms can be done during late pregnancy. Antenatal care clinics constitute a natural and useful environment for recognition of women with depressive symptoms. PMID- 11207492 TI - Conduct of labor and rupture of the sphincter ani. AB - OBJECTIVE: To determine whether the conduct of the second stage of labor and delivery technique influences the incidence of rupture of the anal sphincter. MATERIAL AND METHOD: A total of 1072 primipara delivered vaginally at term at Rigshospitalet in 1998. A questionnaire on prenatal risk factors, conduct of the second stage of labor, and delivery technique was completed by the attending midwife immediately after delivery in 90 cases with rupture of the sphincter and in two subsequent controls (n = 164), matched by use of vacuum extractor and episiotomy. RESULTS: Partial or total sphincter rupture was found in 8.4% of primipara who delivered vaginally, in 20.9% of those delivered by vacuum extraction, and in 6.4% of those with episiotomy only. The prenatal risk factors- maternal age, birth weight, shoulder dystocia, and edema of the perineum were found to have a statistically significant effect on the incidence of rupture of the sphincter ani. In non-instrumental vaginal deliveries easing of the perineum over the caput as it advanced helped prevent a rupture of the anal sphincter. Vacuum extraction performed with the woman in a semi-recumbant position was associated with an increased risk of rupture of the anal sphincter, whereas attention to the perineum during extraction decreased the risk. CONCLUSIONS: The significant effect of prenatal risk factors did not explain a correlation between delivery technique and rupture of the sphincter ani. The present study indicates that a reduction in the incidence of sphincter rupture may be accomplished by improved obstetric care: fewer vacuum extractions and improved delivery technique. PMID- 11207493 TI - Comparison of cervical smears secured with different instruments. AB - BACKGROUND: In this presentation we have compared the results from cytologic samples obtained with the cervical brush and Ayre's wooden spatula, against samples obtained with Acellon Combi. METHODS: One thousand cervical smears were collected. This was a cross-sectional study, where it was decided randomly to use cervical brush for sampling of the endocervix and Ayre's wooden spatula for exocervix or Acellon Combi for both. RESULTS: The combination of the cervical brush and the wooden spatula yielded an acceptable quantity of columnar cells in 71.6% of the cases, during both endocervical and exocervical sampling, while the Acellon Combi yielded an acceptable quantity in 61.7% of the cases (p<0.01). The combination of brush/spatula yielded an acceptable quantity of squamous cells from samples of endocervix and exocervix in 87.5% cases, while with the Acellon device amounted to 77.4% (p<0.001). Highly significant differences in the state of cellular preservation of samples from endocervix obtained with cervical brush technique were found upon comparison to Acellon group. CONCLUSIONS: Henceforth, we believe that the use of the cervical brush and the Ayre wooden spatula increases the quantity and preservation of the cells retrieved during cervical smears compared to Acellon Combi. PMID- 11207495 TI - Fetal position associated with an increased risk of cesarean delivery in nulliparous twin gestations. PMID- 11207494 TI - Hysterectomy on benign indication in Denmark 1988-1998. A register based trend analysis. AB - BACKGROUND: The aims of the study were to describe the trends in Danish hysterectomy rates from 1988 to 1998 for operations done on benign indication. METHODS: Data from all women (n=67,096) undergoing hysterectomy from 1988 to 1998 were obtained from the Danish National Patient Register. Data on the female population distribution were obtained from the Danish National Population Register. RESULTS: During the last 11 years the incidence rate of hysterectomy performed for benign diseases has been stable. However, the rate of women treated surgically for benign diseases of the uterus has increased by 14%. During the study period the number of total abdominal hysterectomies has decreased by 38%, the number of subtotal abdominal hysterectomies has increased by 458%, the number of vaginal hysterectomies has increased by 107% and two new methods of surgical treatment for benign diseases of the uterus have been introduced. Abdominal hysterectomy still accounts for 80% of the total number of hysterectomies performed in Denmark in 1998. The age distribution for all hysterectomies has changed, from a maximum of 36-45 years in 1988 to 46-55 years in 1998. The age maximum for abdominal hysterectomy corresponds to that of all hysterectomies. For vaginal hysterectomy the age maximum is 56 years or older, while it is 36-45 years for laparoscopic hysterectomy. CONCLUSIONS: The incidence rate of hysterectomy was stable during the study period and the age distribution for all hysterectomies has changed. The study showed a change in the choice of surgical methods, although no evidence supports this practice. PMID- 11207497 TI - Naturally conceived twin pregnancy with hyperreactio luteinalis, causing hyperandrogenism and maternal virilization. PMID- 11207496 TI - A case of locked twins successfully treated with nitroglycerin sublingually before manual reposition and vaginal delivery. PMID- 11207498 TI - Adenocarcinoma of the Bartholin's gland in a 34 years old multipara. PMID- 11207499 TI - Pelvic tuberculosis: a case of delayed diagnosis. PMID- 11207500 TI - Pregnancy and labor after TVT-plasty. PMID- 11207501 TI - Reply to P. Vargas letter to the editor: Comparative evaluation of the Misgav Ladach cesarean section with two traditional techniques. The first four years' experience (published in volume 80, 1). PMID- 11207502 TI - Non-closure of peritoneum and adhesions: the repeat cesarean section. PMID- 11207503 TI - Review article: Barrett's oesophagus, dysplasia and pharmacologic acid suppression. AB - Barrett's oesophagus, a significant complication of gastro-oesophageal reflux disease (GERD), is the single most important risk factor for oesophageal adenocarcinoma. The strong association between Barrett's oesophagus and chronic GERD suggests that abnormal oesophageal acid exposure plays an important role in this condition. The progression of Barrett's oesophagus from specialized intestinal metaplasia to dysplasia and finally invasive carcinoma is incompletely understood, but increased and disordered proliferation is a key cellular event. In ex vivo organ culture experiments, cell proliferation is increased after exposure to short pulses of acid, whilst proliferation is reduced in Barrett's oesophagus specimens taken from patients with oesophageal acid exposure normalized by antisecretory therapy. In long-term clinical studies, consistent and profound intra-oesophageal acid suppression with proton pump inhibitors decreases cell proliferation and increases differentiation in Barrett's oesophagus, but the clinical importance of such favourable effects on these surrogate markers is not clear. In clinical practice, proton pump inhibitors relieve symptoms and induce partial regression to squamous epithelium, but abnormal oesophageal acid exposure and the risk for dysplasia or adenocarcinoma persist in many patients. The ability of proton pump inhibitors to suppress acid profoundly and consistently may be critical in the long-term management of Barrett's oesophagus. PMID- 11207504 TI - Review article: tegaserod. AB - Tegaserod (Zelmac), an aminoguanidine indole derivative of serotonin, is a selective partial agonist highly selective for 5-HT(4) receptor with an affinity constant in the nanomolar range. Tegaserod does not cause adverse pharmacodynamic effects, is absorbed rapidly after oral administration and distributes widely into tissues. Pharmacokinetics of oral tegaserod are linear in the 2--12 mg dose range. After oral administration tegaserod is metabolized mainly pre systemically; when absorbed, intact tegaserod is excreted as N-glucuronides mainly via the bile. No clinically relevant drug--drug interactions were identified. Tegaserod has proven safe in toxicity studies. In pharmacodynamic studies, tegaserod stimulated the peristaltic reflex in vitro, increased canine intestinal and colonic motility and transit, reduced visceral afferent firing or sensation in response to distension in animals, and accelerated gastric, small bowel and colonic transit in healthy patients, and small bowel transit in patients with constipation-predominant irritable bowel syndrome. Three large phase III randomized, double-blinded, and placebo-controlled trials were performed predominantly in females (approximately 85%) with constipation predominant irritable bowel syndrome. Overall, phase III results support efficacy as assessed by the subject's global assessment of relief with significant improvement in secondary endpoints such as abdominal pain, bowel frequency and consistency. Tegaserod was well-tolerated; the most frequent adverse event was transient diarrhoea. PMID- 11207505 TI - Review article: a drug therapy for the prevention of variceal haemorrhage. AB - The development of varices is a major complication of cirrhosis, and variceal haemorrhage has a high mortality. There have been major advances in the primary and secondary prevention of variceal haemorrhage over the last 20 years involving endoscopic, radiological and pharmacological approaches. This review concentrates principally on drug therapy, particularly on the numerous haemodynamic studies. Many of these drugs have not been studied in clinical trials, but provide data about the underlying pathogenesis of portal hypertension. Also covered in this review are the randomized controlled trials and meta-analyses that involve a large number of patients. These trials involve relatively few drugs such as non selective beta-blockers and nitrates. Correlations between haemodynamic and clinical parameters are discussed. Despite the recent increase in the use of alternative endoscopic therapies, an effective and well tolerated drug remains a clinically important research goal. PMID- 11207506 TI - Review article: the potential role for photodynamic therapy in the management of upper gastrointestinal disease. AB - Photodynamic therapy involves the activation of an exogenously administered, or an endogenously generated, photosensitizer with light to produce localized tissue destruction. It is an attractive, predominantly endoscopic technique for the palliation of advanced upper gastrointestinal cancer and the eradication of early neoplastic and pre-neoplastic lesions. The nature of the biological response allowing safe healing and the exploitation of tissue threshold effects mean that adjacent tissue damage can be minimized. This review used a database of 368 papers. The nature of the photosensitizer is critical to the depth of tissue damage and the risk of adjacent tissue damage and stricture formation. The generation of protoporphyrin IX following administration of 5-aminolaevulinic acid has proved useful for the treatment of high-grade dysplasia in Barrett's oesophagus. A double-blind randomized placebo controlled trial has confirmed that it is a safe and effective method for the ablation of low-grade dysplasia. The treatment of more advanced lesions requires exogenously administered photo sensitizers. However, recent data indicate that the neoplastic potential remains in some patients and continued follow-up is necessary. Photodynamic therapy can be used to eradicate early neoplasia and palliate advanced cancer, but caution is required before a definitive cure can be claimed. PMID- 11207507 TI - Review article: the prevention of colorectal cancer. AB - Colorectal cancer is a leading cause of cancer mortality in the industrialized world. Survival remains poor because most cases are diagnosed at an advanced stage. It is a preventable disease as colorectal cancers usually develop slowly from an identifiable precursor lesion, the adenoma. The existing strategies for colorectal cancer prevention include dietary prevention, chemoprevention and endoscopic intervention. The exact relationship between diet, particularly fibre, and colorectal cancer remains unclear, with the most recent studies suggesting that dietary fibre may not decrease colorectal cancer risk as previously thought. Non-steroidal anti-inflammatory drugs have been shown to have a protective effect against colorectal cancer, but the adverse effect profile of the non COX-2 selective drugs, particularly the risk of gastrointestinal haemorrhage, precludes their widespread use. There is increasing evidence that colorectal cancer incidence and mortality can be decreased from endoscopic polypectomy and early detection of cancer. Faecal occult blood testing in the general population ('average-risk') has been shown in randomized trials to decrease mortality from colorectal cancer by 15--33%. Long-term results of randomized trials of the effectiveness of flexible sigmoidoscopy and colonoscopy screening in the general population are awaited. Targeting high risk individuals may also be an effective and efficient way to decrease the colorectal cancer burden. As many as 15--30% of colorectal cases may be due to hereditary factors. Individuals with one or two direct relatives affected are at moderate risk for colorectal cancer (empirical lifetime mortality from colorectal cancer approximately 10%) and approximately 2- 3% of cases arise in individuals harbouring highly penetrant autosomal dominant mutations, which puts them at high-risk for colorectal cancer. Surveillance colonoscopy is offered to individuals at moderate and high risk for colorectal cancer. PMID- 11207508 TI - Review article: Mycobacterium avium subsp. paratuberculosis as one cause of Crohn's disease. AB - A number of theories regarding the aetiology of Crohn's disease have been proposed. Diet, infections, other unidentified environmental factors and immune disregulation, all working under the influence of a genetic predisposition, have been viewed with suspicion. Many now believe that Crohn's disease is a syndrome caused by several aetiologies. The two leading theories are the infectious and autoimmune theories. The leading infectious candidate is Mycobacterium avium subspecies paratuberculosis (Mycobacterium paratuberculosis), the causative agent of Johne's disease, an inflammatory bowel disease in a variety of mammals including cattle, sheep, deer, bison, monkeys and chimpanzees. The evidence to support M. paratuberculosis infection as a cause of Crohn's disease is mounting rapidly. Technical advances have allowed the identification and/or isolation of M. paratuberculosis from a significantly higher proportion of Crohn's disease tissues than from controls. These methodologies include: (i) improved culture techniques; (ii) development of M. paratuberculosis-specific polymerase chain reaction assays; (iii) development of a novel in situ hybridization method; (iv) efficacy of macrolide and anti-mycobacterial drug therapies; and (v) discovery of Crohn's disease-specific seroreactivity against two specific M. paratuberculosis recombinant antigens. The causal role for M. paratuberculosis in Crohn's disease and correlation of infection with specific stratification(s) of the disorder need to be investigated. The data implicating Crohn's as an autoimmune disorder may be viewed in a manner that supports the mycobacterial theory. The mycobacterial theory and the autoimmune theory are complementary; the first deals with the aetiology of the disorder, the second deals with its pathogenesis. Combined therapies directed against a mycobacterial aetiology and inflammation may be the optimal treatment of the disease. PMID- 11207510 TI - Meta-analysis of smooth muscle relaxants in the treatment of irritable bowel syndrome. AB - AIM: To update previous overviews of placebo-controlled double-blind trials assessing the efficacy and tolerance of smooth muscle relaxants in irritable bowel syndrome. METHODS AND TRIALS: A total of 23 randomized clinical trials were selected for meta-analyses of their efficacy and tolerance. Six drugs were analysed: cimetropium bromide (five trials), hyoscine butyl bromide (three trials), mebeverine (five trials), otilium bromide (four trials), pinaverium bromide (two trials) and trimebutine (four trials). The total number of patients included was 1888, of which 945 received an active drug and 943 a placebo. RESULTS: The mean percentage of patients with global improvement was 38% in the placebo group (n=925) and 56% in the myorelaxant group (n=927), in favour of myorelaxants with a mean odds ratio of 2.13, P < 0.001 (95% CI: 1.77--2.58) and a mean risk difference of 22% P < 0.001 (95% CI: 13--32%). The percentage of patients with pain improvement was 41% in the placebo group (n=568) and 53% in the myorelaxant group (n=567): odds ratio 1.65, P < 0.001 (95% CI: 1.30--2.10) and risk difference 18%, P < 0.001 (95% CI: 7--28%). There was no significant difference for adverse events. CONCLUSION: Myorelaxants are superior to placebo in the management of irritable bowel syndrome. PMID- 11207509 TI - Esomeprazole 20 mg maintains symptom control in endoscopy-negative gastro oesophageal reflux disease: a controlled trial of 'on-demand' therapy for 6 months. AB - BACKGROUND: Most patients with gastro-oesophageal reflux disease (GERD), regardless of endoscopic status, suffer symptomatic relapse within 6 months of stopping acid suppressant therapy. AIM: To assess the efficacy of 'on-demand' treatment of GERD with esomeprazole, the first proton pump inhibitor developed as an optical isomer. METHODS: In this multicentre, double-blind study, 342 endoscopy-negative GERD patients demonstrating complete resolution of heartburn during the final week of a 4-week treatment period with esomeprazole 20 mg or omeprazole 20 mg once daily were randomized to receive esomeprazole 20 mg or placebo on demand (maximum of one dose per day) for a further 6 months. Use of rescue antacids was permitted. RESULTS: All 342 patients (191 males), aged 19-79 (mean 49) years, were evaluable in the intention-to-treat analysis. The proportion of patients who discontinued treatment due to insufficient control of heartburn was significantly higher among placebo compared to esomeprazole recipients (51% vs. 14%; P < 0.0001). Patients randomized to esomeprazole on demand therapy remained in the study longer than those in the placebo group (mean 165 vs. 119 days). Over 50% took the study medication for periods of 1--3 consecutive days (esomeprazole) or 4--13 consecutive days (placebo). Use of antacids was > 2-fold higher among placebo recipients. The frequency of adverse events was similar in the two groups, when adjusted for time spent in the study, as were the clinical laboratory profiles. CONCLUSIONS: On-demand therapy with esomeprazole 20 mg is effective and well tolerated in maintaining symptom control in endoscopy-negative GERD. PMID- 11207511 TI - Minimal renal dysfunction in inflammatory bowel disease is related to disease activity but not to 5-ASA use. AB - BACKGROUND: Conflicting data exist about proteinuria in inflammatory bowel diseases. It is still unclear whether the occurrence of proteinuria in inflammatory bowel disease patients is an extra-intestinal manifestation of disease or the result of adverse effects to medication, especially to aminosalicylates (ASA). METHODS: A total of 95 patients (51 with Crohn's disease and 44 with ulcerative colitis) were enrolled in the study. Disease activity was assessed by Crohn's Disease Activity Index (CDAI) or the Truelove index, respectively. Urine was collected over 24 h and protein excretion of specific marker proteins for tubular (alpha 1-microglobulin-alpha 1-MG) and glomerular (albumin-Alb, Immunoglobulin G-IgG) dysfunction was measured using a highly sensitive immunoluminometric assay. RESULTS: Out of 51 Crohn's disease patients, 20 showed elevated urinary alpha 1-MG. The amount of alpha 1-MGuria was strongly correlated to the CDAI (r=0.6, P < 0.001). Only four Crohn's disease patients showed slightly elevated values for glomerular proteins in urine. Similar results were obtained for ulcerative colitis: whereas only two ulcerative colitis patients showed albuminuria, tubular proteinuria was detected in 28 out of 44 ulcerative colitis patients. Proteinuria was strongly dependent on disease activity (P < 0.01) but was not related to ASA treatment. CONCLUSIONS: Proteinuria of tubular marker proteins occurs in the majority of inflammatory bowel disease patients and is related to disease activity rather than to ASA treatment. Tubular proteinuria seems to reflect a renal extra-intestinal manifestation of inflammatory bowel disease and may serve as a new relevant marker of disease activity. PMID- 11207512 TI - Oral tacrolimus long-term therapy in patients with Crohn's disease and steroid resistance. AB - AIM: To report the results of a prospective, open-label, uncontrolled study in 13 patients affected by Crohn's disease with resistance to steroids. METHODS: The patients were treated long-term with oral tacrolimus, aiming to both resolve acute attacks and maintain remission. Tacrolimus was administered at the dose of 0.1--0.2 mg.day/kg and adjusted in order to achieve levels of 5--10 ng/mL; only mesalazine was continued concomitantly. Steroids and total parenteral nutrition were tapered when appropriate. RESULTS: Median treatment was 27.3 months. Only one patient dropped out due to adverse events. Crohn's disease activity index score significantly decreased after 6 months in 11 patients; for 1 year in nine of them, and 7 years in two of them. The inflammatory bowel disease life-quality questionnaire score significantly increased over the same periods. A marked drop in hospitalizations was recorded. In three out of six patients complete closure of fistulas occurred. Tacrolimus allowed total parenteral nutrition to be withdrawn in three out of five patients. Supplementation with low-dose steroids was required in five patients. Two patients underwent surgery. CONCLUSIONS: Tacrolimus therapy appears to be associated with both short- and long-term benefits, and may represent a therapeutic option in Crohn's disease when conventional therapies fail. This study encourages its use in controlled trials. PMID- 11207513 TI - Non-Helicobacter pylori bacterial flora during acid-suppressive therapy: differential findings in gastric juice and gastric mucosa. AB - BACKGROUND: Intragastric growth of non-Helicobacter pylori bacteria commonly occurs during acid-suppressive therapy. The long-term clinical consequences are still unclear. AIM: To investigate the luminal and mucosal bacterial growth during gastric acid inhibition, in relation to the type and duration of acid inhibitory treatment, as well as to concomitant H. pylori infection. METHODS: A total of 145 patients on continuous acid inhibition with either proton pump inhibitors (n=109) or histamine2-receptor antagonists (H(2)RAs, n=36) for gastro oesophageal reflux disease, and 75 dyspeptic patients without acid inhibition (control group) were included. At endoscopy, fasting gastric juice was obtained for pH measurement and bacteriological culture. Gastric biopsy specimens were examined for detection of H. pylori (immunohistochemistry) and of non-H. pylori bacteria (modified Giemsa stain-positive and immunohistochemistry-negative at the same location). RESULTS: Non-H. pylori flora was detected in the gastric juice of 92 (41.8%) patients and in the gastric mucosa of 109 (49.6%) patients. In gastric juice, prevalence rate for non-H. pylori bacteria was higher in patients taking proton pump inhibitors than controls and those taking H(2)RAs (58.7% vs. 22.6% and vs. 30.6%, P < 0.0001 and P < 0.003, respectively), but did not differ statistically between H(2)RAs and controls. In gastric mucosa, prevalence rates for non-H. pylori bacteria were higher in patients taking proton pump inhibitors and H(2)RAs than in the controls (antrum: 46.9% and 48.6% vs. 25%, P < 0.05 for both; corpus: 52.2% and 56.8% vs. 23.7%, P < 0.001 for both), but did not differ between proton pump inhibitors and H(2)RAs. Both luminal and mucosal growth of non-H. pylori bacteria were significantly greater in H. pylori-positive than negative patients taking proton pump inhibitors (P < 0.05 for both). Luminal growth of non-H. pylori flora increased with the intragastric pH level, whilst mucosal bacterial growth increased with the duration of acid inhibition. CONCLUSIONS: Non-H. pylori flora not only contaminates the gastric juice but also colonizes the gastric mucosa of a large proportion of patients treated long-term with acid inhibition. The relationship between H. pylori and non-H. pylori bacteria in the pathogenesis of atrophic gastritis and gastric cancer needs further elucidation. PMID- 11207514 TI - Evaluation of a novel continuous real time (13)C urea breath analyser for Helicobacter pylori. AB - AIM: To evaluate the sensitivity and specificity of a new (13)C urea breath test, Oridion BreathID, for the diagnosis of Helicobacter pylori. METHODS: A total of 97 consecutive symptomatic patients referred for upper endoscopy were included in the 'pre-therapy' part of the study. After endoscopy the patients were analysed for H. pylori by Oridion BreathID. BreathID continuously sampled the subject's breath for 20 min, and displayed the results on the BreathID screen in real time. Results of the BreathID were compared with the 'gold standard' (rapid urease test and histology). We also prospectively tested the validity of BreathID in comparison to isotope ratio mass spectrometry, in 40 patients referred to monitor the efficacy of H. pylori eradication treatment. RESULTS: Complete agreement was observed between the 'gold standard' and the Breath ID test in 96.9% (94 out of 97) of the patients. The sensitivity and specificity of BreathID were 97.8% and 96.1%, respectively. The correlation between BreathID and isotope ratio mass spectrometry breath test was 100%. CONCLUSIONS: The Oridion BreathID has comparable sensitivity and specificity to the claims of the currently available urea breath tests. Furthermore, BreathID has the potential advantages of ease of use with minimal medical staff requirement, and real time rapid results (20 min maximum) which may make the BreathID preferable to other urea breath test assays. PMID- 11207515 TI - Post-treatment diagnostic accuracy of a new enzyme immunoassay to detect Helicobacter pylori in stools. AB - BACKGROUND: Helicobacter pylori has attracted increasing attention among gastroenterologists because of its pathogenic potential, stimulating the search for non-invasive diagnostic tests. AIMS: In this study the efficacy of a new enzyme immunoassay designed to detect H. pylori antigens in stools (HpSA) was evaluated before and after eradication therapy. METHODS: HpSA was performed on stool samples collected from 268 patients whose H. pylori status was defined on the basis of concordant results for the (13)C-urea breath test, rapid urease test and histology. The H. pylori-positive patients were treated with a 1-week triple therapy to eradicate the infection. One (T30) and 3 months (T90) after the end of therapy, (13)C-urea breath test and HpSA were repeated in the treated patients. RESULTS: The overall diagnostic accuracy of HpSA at T30 (83%, 95% confidence interval (CI) 77--89%) was significantly lower in comparison to the values obtained at baseline (94%, 95% CI: 91--97%) and at T90 (97%, 95% CI: 94--99%). No significant difference was found between the diagnostic accuracy of HpSA at baseline and at T90 (P=0.253). CONCLUSIONS: The present data suggest that HpSA provides a low diagnostic accuracy when used shortly after treatment. It needs a longer period of follow-up (8--12 weeks) to reach a reliability comparable to the (13)C-urea breath test. PMID- 11207516 TI - One-week ranitidine bismuth citrate-based triple therapy for the eradication of Helicobacter pylori in Hong Kong with high prevalence of metronidazole resistance. AB - AIM: To compare 1-week ranitidine bismuth citrate-based (RBC) triple therapy vs. omeprazole-based (O) triple therapy for the eradication of Helicobacter pylori infection in Hong Kong with high prevalence of metronidazole resistance. METHODS: Patients with non-ulcer dyspepsia and H. pylori infection were randomized to receive either: (i) RBCCM: ranitidine bismuth citrate (pylorid) 400 mg, clarithromycin 250 mg and metronidazole 400 mg; or (ii) OCM: omeprazole 20 mg, clarithromycin 250 mg and metronidazole 400 mg, each given twice daily for 1 week. Endoscopy (CLO test, histology and culture) and 13C-urea breath test were performed before randomization and 6 weeks after drug treatment. RESULTS: A total of 180 patients were randomized. H. pylori eradication rates (intention-to-treat, n=180/per protocol, n=166) were 83%/92% for RBCCM and 66%/70% for OCM (P=0.01, intention-to-treat and P=0.001, per protocol, respectively). RBCCM treatment was unaffected by metronidazole susceptibility and achieved a significantly higher eradication rate in metronidazole-resistant cases (89%) than the OCM group (45%, P=0.0064). CONCLUSION: One-week ranitidine bismuth citrate-based triple therapy is significantly better than omeprazole-based triple therapy for the eradication of H. pylori infection, especially in metronidazole-resistant cases. It is an effective regimen for the eradication of H. pylori infection in regions with a high prevalence of metronidazole resistance. PMID- 11207517 TI - Clarithromycin vs. furazolidone in quadruple therapy regimens for the treatment of Helicobacter pylori in a population with a high metronidazole resistance rate. AB - BACKGROUND: The eradication of Helicobacter pylori plays a pivotal role in the treatment of peptic ulcer disease. Metronidazole resistance, common in Iran, is claimed to be a major reason for the failure of metronidazole-containing regimens. Both clarithromycin and furazolidone are potential alternatives for metronidazole. AIM: To assess and compare the effectiveness of clarithromycin- and furazolidone-based regimens in eradicating H. pylori in a population with a high metronidazole resistance rate. METHODS: Patients with proven duodenal ulcer and H. pylori infection were randomly assigned to one of two groups. The patients received 2 weeks of omeprazole 20 mg b.d., amoxicillin 1000 mg b.d, bismuth subcitrate 240 mg b.d. and either clarithromycin 500 mg b.d. (the OABC group) or furazolidone 200 mg b.d. (the OABF group). RESULTS: A total of 118 patients were randomized, 55 in the OABC group and 63 in the OABF group. The intention-to-treat eradication rate was 84% and 85% for the OABF and OABC groups, respectively. The per protocol eradication rates were 90% for both groups. CONCLUSIONS: OABC and OABF are both effective in eradicating H. pylori in areas where metronidazole resistance is a problem. OABF is a good alternative in the face of growing resistance to clarithromycin in developed countries, and is attractive for developing countries where clarithromycin is not readily available. PMID- 11207518 TI - Five-day proton pump inhibitor-based quadruple therapy regimen is more effective than 7-day triple therapy regimen for Helicobacter pylori infection. AB - BACKGROUND: There have been no reports that describe whether 5-day quadruple therapy (rabeprazole + amoxicillin + clarithromycin + metronidazole; RACM) could substitute for standard 7-day triple therapy as a first-line therapy for Helicobacter pylori. PATIENTS AND METHODS: This study was designed as a randomized prospective single centre study. A total of 160 H. pylori-positive patients who had not received therapy were given either a 5-day RACM regimen (n=80, rabeprazole 20 mg b.d., amoxicillin 750 mg b.d., clarithromycin 200 mg b.d. and metronidazole 250 mg b.d.) or a 7-day RAC regimen (n=80, rabeprazole 20 mg b.d., amoxicillin 750 mg b.d. and clarithromycin 200 mg b.d.). Cure of the infection was assessed by a (13)C urea breath test 1 month after the completion of therapy. RESULTS: The eradication rates of the 5-day RACM regimen and the 7 day RAC regimen were 93% (95% CI: 84--97%) and 81% (95% CI: 71--89%) by intention to-treat analysis, 94% (95% CI: 86--98%) and 83% (95% CI: 73--91%) by all patients-treated analysis analysis and 95% (95% CI: 87--98%; P < 0.05) and 82% (95% CI: 72--90%) by per protocol analysis, respectively. No serious adverse effect was observed, and 99% of the patients reported complete compliance. CONCLUSIONS: The cure rate of the 5-day RACM regimen was more effective than the 7-day RAC regimen, suggesting that this regimen could be preferable as a first line therapy for H. pylori infection. PMID- 11207535 TI - Cellular microbiology - a research agenda and an emerging discipline. PMID- 11207519 TI - Validation of a new immunoblot assay for the diagnosis of Helicobacter pylori in the Asian population. AB - BACKGROUND: Performance of commercial serological tests for Helicobacter pylori varies in different populations, largely due to strain heterogeneity and variations in antigenic preparations. Currently available serology tests often show sub-optimal accuracy when used for Asian patients. AIM: This study evaluated a recombinant antigen-based immunoblot for the diagnosis of H. pylori infection in Chinese patients, and compared it with a conventional ELISA test. METHODS: Dyspeptic patients referred for diagnostic endoscopy were recruited. The gold standard for H. pylori infection was based on two or more positive results among rapid urease test, histology and (13)C-urea breath test. Serological diagnosis of H. pylori infection was conducted by an ELISA test (pylori DTect; Diagnostic Technology) and an immunoblotting against a novel recombinant antigen (C1S; Genelab), which was constructed by immunological screening of the genomic DNA library of H. pylori. RESULTS: A total of 87 patients were evaluated and H. pylori infection was diagnosed in 40 (46%) by the reference tests. The sensitivities of the ELISA and immunoblot were 80% (95% CI: 64--91%) and 90% (95% CI: 76--97%), whilst the specificities were 96% (95% CI: 86--96%) and 87% (95% CI: 74--95%), respectively. The respective likelihood ratios of the two tests were 18.6 and 7.0. CONCLUSIONS: Satisfactory performance is obtained by the use of the new recombinant antigen-based immunoblot for diagnosing H. pylori infection in Chinese patients. PMID- 11207536 TI - Cellular Microbiology is launched. PMID- 11207537 TI - Identification of the intimin-binding domain of Tir of enteropathogenic Escherichia coli. AB - Enteropathogenic Escherichia coli (EPEC) attaches intimately to mammalian cells via a bacterial outer membrane adhesion molecule, intimin, and its receptor in the host cell membrane, Tir. Tir is a bacterial protein translocated into the host cell membrane and tyrosine phosphorylated after insertion. Tir-intimin binding induces organized actin polymerization beneath the adherent bacteria, resulting in the formation of pedestal-like structures. A series of Tir deletion derivatives were constructed to analyse which Tir domains are involved in intimin binding. We have localized the intimin-binding domain (IBD) of Tir using a yeast two-hybrid system and a gel-overlay approach to a region of 109 amino acids that is predicted to be exposed on the surface of the plasma membrane. A truncated Tir protein lacking this domain was translocated to the host cell membrane and tyrosine phosphorylated, but failed to bind intimin or to induce either actin polymerization or Tir accumulation beneath the bacteria. These results indicate that only a small region of Tir is needed to bind intimin and support the predicted topology for Tir, with both N- and C-terminal regions in the mammalian cell cytosol. They also confirm that Tir-intimin interactions are needed for cytoskeletal organization. We have also identified N-terminal regions involved in Tir stability and Tir secretion to the media. PMID- 11207538 TI - Impaired recruitment of the small GTPase rab7 correlates with the inhibition of phagosome maturation by Leishmania donovani promastigotes. AB - We have shown recently that one of the survival strategies used by Leishmania donovani promastigotes during the establishment of infection in macrophages consists in inhibiting phagosome-endosome fusion. This inhibition requires the expression of lipophosphoglycan (LPG), the predominant surface glycoconjugate of promastigotes, as parasites expressing truncated forms of LPG reside in phagosomes that fuse extensively with endocytic organelles. In the present study, we developed a single-organelle fluorescence analysis approach to study and analyse the intracellular trafficking of 'fusogenic' and 'low-fusogenic' phagosomes induced by an LPG repeating unit-defective mutant (Ipg2 KO) or by wild type L. donovani promastigotes respectively. The results obtained indicate that phagosomes containing mutant parasites fuse extensively with endocytic organelles and transform into phagolysosomes by losing the early endosome markers EEA1 and transferrin receptor, and acquiring the late endocytic and lysosomal markers rab7 and LAMP1. In contrast, a majority of 'low-fusogenic' phagosomes containing wild type L. donovani promastigotes do not acquire rab7, wheres they acquire LAMP1 with slower kinetics. These results suggest that L. donovani parasites use LPG to restrict phagosome-endosome fusion at the onset of infection in order to prevent phagosome maturation. This is likely to permit the transformation of hydrolase sensitive promastigotes into hydrolase-resistant amastigotes within a hospitable vacuole not displaying the harsh environment of phagolysosomes. PMID- 11207539 TI - Biogenesis of Salmonella typhimurium-containing vacuoles in epithelial cells involves interactions with the early endocytic pathway. AB - In epithelial cells, the intracellular pathogen Salmonella typhimurium resides and replicates within a unique cytoplasmic organelle, the Salmonella-containing vacuole (SCV). In vitro studies have shown that the SCV is a dynamic organelle that selectively acquires lysosomal glycoproteins (Igps) without fusing directly with lyosomes. Here, we have investigated early events in SCV biogenesis using immunofluorescence microscopy and epitope-specific flow cytometry. We show that proteins specific to the early endocytic pathway, EEA1 and transferrin receptor (TR), are present on early SCVs. The association of these proteins with SCVs is transient, and both proteins are undetectable at later time points when Igp and vATPase are acquired. Analysis of the fraction of SCVs containing both TR and lamp-1 showed that TR is lost from SCVs as the Igp is acquired, and that these processes occur progressively and not as the result of a single fusion/fission event. These experiments reveal a novel mechanism of SCV biogenesis, involving previously undetected initial interactions with the early endocytic pathway followed by the sequential delivery of Igp. The pathway does not involve interactions with the late endosome/prelysosome and is distinct from traditional phagocytic and endocytic pathways. Our study indicates that intracellular S. typhimurium occupies a unique niche, branching away from the traditional endocytic pathway between the early and late endosomal compartments. PMID- 11207540 TI - Signalling and cellular specificity of airway nitric oxide production in pertussis. AB - Bordetella pertussis, the aetiological agent of whooping cough (pertussis), causes selective destruction of ciliated cells of the human airway mucosa. In a hamster tracheal organ culture model, B. pertussis causes identical cytopathology as does tracheal cytotoxin (TCT), a glycopeptide released by the bacterium. The damage caused by B. pertussis or TCT has been shown to be mediated via nitric oxide (NO*). Using immunofluorescence detection of the cytokine-inducible NO synthase (iNOS; NOS type II), we determined that B. pertussis induced epithelial NO* production exclusively within non-ciliated cells. This epithelial iNOS activation could be reproduced by the combination of TCT and endotoxin. However, neither TCT alone nor endotoxin alone was capable of inducing epithelial iNOS. This result mirrors the synergistic activity of TCT and endotoxin exhibited in monolayer cultures of tracheal epithelial cells. Therefore, TCT and endotoxin are both important virulence factors of B. pertussis, combining synergistically to cause the specific epithelial pathology of pertussis. PMID- 11207541 TI - CpG-DNA upregulates the major acute-phase proteins SAA and SAP. AB - The acute-phase response is an immediate reaction of the host against invading microorganisms. We show here that oligodeoxynucleotides (ODNs) containing a CpG motif rapidly induce the major murine acute-phase proteins in vivo, i.e. serum amyloid A (SAA) and serum amyloid P (SAP). Serum levels of these proteins are elevated within 12 h and peak at 24 h after the injection of CpG-ODN or endotoxin. Liver cells produce the proteins with the same kinetics. Injection of interleukin 6 (IL-6), IL-1beta and tumour necrosis factor alpha (TNF-alpha) induces SAA and SAP in vivo, but the CpG-ODN-mediated induction does not depend on the presence of the TNF receptor p55, as the acute-phase response in TNF receptor p55-deficient mice does not differ from that of wild-type mice. Aside from CpG-ODN, bacterial genomic DNA also induces the acute-phase response in LPS resistant C3H/Hej mice. The induction of the major acute-phase proteins SAA and SAP is blocked by the simultaneous injection of CpG-ODN together with D galactosamine (D-GalN). As D-GalN sensitizes the host for the toxic effects of TNF-alpha, a possible mechanism could be the prevention of synthesis of the major acute-phase proteins SAA and SAP. PMID- 11207542 TI - Channels formed by subnanomolar concentrations of the toxin aerolysin trigger apoptosis of T lymphomas. AB - Aerolysin is a channel-forming toxin that binds to glycosylphosphatidylinositol (GPI)-anchored proteins, such as Thy-1, on target cells. Here, we show that subnanomolar concentrations of aerolysin trigger apoptosis of T lymphomas. Using inactive aerolysin variants, we determined that apoptosis was not directly triggered by binding to GPI-anchored receptors, nor was it caused by receptor clustering induced by toxin oligomerization. Apoptosis was caused by the production of a small number of channels in the cell membrane. Channel formation resulted in a rapid increase in intracellular calcium, which may have been the signal for apoptosis. Overexpression of the antiapoptotic protein bcl-2 blocked aerolysin-induced apoptosis, although this effect was overcome at higher toxin concentrations. PMID- 11207543 TI - Toxin entry: how bacterial proteins get into mammalian cells. AB - Certain bacteria secrete protein toxins that catalytically modify and disrupt essential processes in mammalian cells, often leading to cell death. As the substrates modified by these toxins are located in the mammalian cell cytosol, a catalytically active toxin polypeptide must reach this compartment in order to act. The toxins bind to receptors on the surface of susceptible cells and enter them by endocytic uptake. Endocytosed toxins initially accumulate in endosomes, where some of these proteins take advantage of the acidic environment within these organelles to form, or contribute to the formation of, protein-conducting channels through which the catalytic polypeptide is able to translocate into the cytosol. Other toxins are unable to respond to low pH in this way and must undergo intracellular vesicular transport to reach a compartment where pre existing protein-conducting channels occur and can be exploited for membrane translocation--the endoplasmic reticulum. In this way, cell entry by this second group of toxins demonstrates that the secretory pathway of mammalian cells is completely reversible. PMID- 11207544 TI - Molecular response of gastric epithelial cells to Helicobacter pylori-induced cell damage. AB - Infection with the Gram-negative bacterium Helicobacter pylori leads to different clinical and pathological outcomes in humans, including chronic gastritis, peptic ulcer disease and adenocarcinoma of the stomach. H. pylori-induced damage to gastric mucosal cells is controlled by bacterial virulence factors encoded by genes of the cag pathogenicity island, which trigger the inflammatory response of the host through the activation of nuclear factor kappaB-dependent gene transcription. Also, H. pylori infection impairs the processes of gastric mucosal healing through inhibition of epidermal growth factor receptor-dependent signal transduction pathways and induction of apoptosis. H. pylori infection may influence the progression from chronic gastritis to gastric adenocarcinoma by stimulating cell proliferation and growth factor expression, inhibiting apoptosis and increasing the DNA mutation rate of infected gastric mucosa. PMID- 11207545 TI - Fibronectin-binding protein acts as Staphylococcus aureus invasin via fibronectin bridging to integrin alpha5beta1. AB - The ability of Staphylococcus aureus to invade mammalian cells may explain its capacity to colonize mucosa and to persist in tissues after bacteraemia. To date, the underlying molecular mechanisms of cellular invasion by S. aureus are unknown, despite its high prevalence and difficulties in treatment. Here, we show cellular invasion as a novel function for an S. aureus adhesin, previously implicated solely in attachment. S. aureus, but not S. epidermidis, invaded epithelial 293 cells in a temperature- and F-actin-dependent manner. Formaldehyde fixed and live bacteria were equally invasive, suggesting that no active bacterial process was involved. All clinical S. aureus isolates analysed, but only a subset of laboratory strains, were invasive. Fibronectin-binding proteins (FnBPs) acted as S. aureus invasins, because: (i) FnBP deletion mutants of invasive laboratory strains lost invasiveness; (ii) expression of FnBPs in noninvasive strains conferred invasiveness; and (iii) the soluble isolated fibronectin-binding domain of FnBP (D1-D4) completely blocked invasion. Integrin alpha5beta1 served as host cell receptor, which interacted with staphylococcal FnBPs through cellular or soluble fibronectin. FnBP-deficient mutants lost invasiveness for epithelial cells, endothelial cells and fibroblasts. Thus, fibronectin-dependent bridging between S. aureus FnBPs and host cell integrin alpha5beta1 is a conserved mechanism for S. aureus invasion of human cells. This may prove useful in developing new therapeutic and vaccine strategies for S. aureus infections. PMID- 11207546 TI - The Chlamydia trachomatis IncA protein is required for homotypic vesicle fusion. AB - Chlamydiae replicate within an intracellular vacuole, termed an inclusion, that is non-fusogenic with vesicles of the endosomal or lysosomal compartments. Instead, the inclusion appears to intersect an exocytic pathway from which chlamydiae intercept sphingomyelin en route from the Golgi apparatus to the plasma membrane. Chlamydial protein synthesis is required to establish this interaction. In an effort to identify those chlamydial proteins controlling vesicle fusion, we have prepared polyclonal antibodies against several Chlamydia trachomatis inclusion membrane proteins. Microinjection of polyclonal antibodies against three C. trachomatis inclusion membrane proteins, IncA, F and G, into the cytosol of cells infected with C. trachomatis demonstrates reactivity with antigens on the cytoplasmic face of the inclusion membrane, without apparent inhibition of chlamydial multiplication. Microinjection of antibodies against the C. trachomatis IncA protein, however, results in the development of an aberrant multilobed inclusion structure remarkably similar to that of C. psittaci GPIC. These results suggest that the C. trachomatis IncA protein is involved in homotypic vesicle fusion and/or septation of the inclusion membrane that is believed to accompany bacterial cell division in C. psittaci. This proposal is corroborated by the expression of C. trachomatis and C. psittaci IncA in a yeast two-hybrid system to demonstrate C. trachomatis, but not C. psittaci, IncA interactions. Despite the inhibition of homotypic fusion of C. trachomatis inclusions, fusion of sphingomyelin-containing vesicles with the inclusion was not suppressed. PMID- 11207547 TI - Visualization of harpin secretion in planta during infection of apple seedlings by Erwinia amylovora. AB - Erwinia amylovora is a Gram-negative pathogenic bacterium that infects pear and apple trees as well as other plants from the Rosaceae family. E. amylovora pathogenicity is dependent on a functional Hrp type III secretion system. Harpin, a protein playing a major role in virulence, has been shown to be exported in vitro via the type III secretion apparatus. The data presented here focus on harpin detection in planta after infection of apple seedlings with the wild-type strain CFPB 1430. Using a specific harpin antiserum, harpin was not detected inside the host plant cells, but was found associated with the bacteria and secreted. The extracellular localization of harpin is in agreement with the physiological effects induced by purified harpin when applied as an exogenous elicitor. Harpin was not found associated with the host plant cell wall, a result that weakens its postulated role in cell wall loosening. A differential labelling was observed at the bacterial level: for some bacteria, harpin was exclusively cytoplasmic, whereas in others, it appeared as small patches over the bacterial outer membrane or associated with extracellular linear structures. All the bacteria present within the same area were similarly labelled, suggesting co ordination in the secretion process. All observations suggest that harpin is synthesized in the bacterial cytoplasm and that secretion occurs from this cytoplasmic pool upon sensing of a plant or bacterial signal. PMID- 11207548 TI - Inhibition of Shigella flexneri-induced transepithelial migration of polymorphonuclear leucocytes by cadaverine. AB - Dysentery caused by Shigella species is characterized by infiltration of polymorphonuclear leucocytes (PMNs) into the colonic mucosa. Shigella spp. evolved into pathogens by the acquisition of virulence genes and by the deletion of 'antivirulence' genes detrimental to its pathogenic lifestyle. An example is cadA (encoding lysine decarboxylase), which is uniformly absent in Shigella spp., whereas it is present in nearly all isolates of the closely related non-pathogen Escherichia coli. Here, using monolayers of T84 cells to model the human intestinal epithelium, we determined that the introduction of cadA into S. flexneri and the expression of lysine decarboxylase attenuated the bacteria's ability to induce PMN influx across model intestinal epithelium. Such inhibition was caused by cadaverine generated from the decarboxylation of lysine. Cadaverine treatment of model intestinal epithelia specifically inhibited S. flexneri induction of PMN transepithelial migration, while having no effect on the ability of Salmonella or enteropathogenic E. coli (EPEC) to induce PMN migration. These observations not only provide insight into mechanisms of S. flexneri pathogen evolution and pathogenesis, but also suggest a potential for the use of cadaverine in the treatment of dysentery. PMID- 11207550 TI - Molecular analysis of neisserial Opa protein interactions with the CEA family of receptors: identification of determinants contributing to the differential specificities of binding. AB - The carcinoembryonic antigen (CEA) gene family members, CEACAM1, CEACAM3, CEACAM5 and CEACAM6, are bound by the Opa outer membrane proteins of pathogenic Neisseria spp., whereas CEACAM8 is not. In this study, we demonstrate that the closely related CEACAM4 and CEACAM7, which are also members of the CEA family, are not Opa receptors. We exploited the high conservation between CEACAM6 and CEACAM8 to generate an extensive set of chimeric receptors in order to delineate the sequences necessary for Opa binding. Using a transfection-based infection system, we showed that binding of Opa52 involves residues 27-42, which are predicted to form beta-strand C and short loops adjacent to it, and residues lying between amino acids 60 and 108 in the amino-terminal domain. The replacement of residues 27-29 in CEACAM6 with the CEACAM1 or CEACAM5 sequences generated recombinant CEACAM6 receptors that are bound by CEACAM1/CEACAM5-specific Opa variants. Together, our data demonstrate that Opa proteins bind to residues exposed on the GFCC' face of the N-terminal domain of CEACAM receptors, and identify an amino acid triplet sequence that is responsible for the differential binding of Opa proteins to CEACAM1, CEACAM5 and CEACAM6. PMID- 11207551 TI - The secreted IpaB and IpaC invasins and their cytoplasmic chaperone IpgC are required for intercellular dissemination of Shigella flexneri. AB - Invasion of epithelial cells by Shigella flexneri involves entry and dissemination. The main effectors of entry, IpaB and IpaC, are also required for contact haemolytic activity and escape from the phagosome in infected macrophages. These proteins are stored in the cytoplasm in association with the chaperone IpgC, before their secretion by a type III secretion apparatus is activated by host cells. We used a His-tagged IpgC protein to purify IpgC containing complexes and showed that only IpaB and IpaC are associated with IpgC. Plasmids expressing His6-IpgC either alone or together with IpaB or IpaC under the control of an IPTG-inducible lac promoter were introduced into ipgC, ipaB or ipaC mutants. Induction of expression of the recombinant plasmid-encoded proteins by IPTG allowed bacteria to enter epithelial cells, and the role of these proteins in dissemination was investigated by incubating infected cells in either the absence or the presence of IPTG. The size of plaques produced by recombinant strains on cell monolayers was regulated by IPTG, indicating that IpgC, IpaB and IpaC were each required for efficient dissemination. Electron microscopy analysis of infected cells indicated that these proteins were necessary for lysis of the membrane of the protrusions during cell-to-cell spread. PMID- 11207549 TI - Involvement of alpha5beta1 integrins in interleukin 8 production induced by oral viridans streptococcal protein I/IIf in cultured endothelial cells. AB - Using human endothelial cells, we define a mechanism that accounts for the induction of interleukin 8 (IL-8) by protein I/IIf, an adhesin from Streptococcus mutans serotype f. We report that protein I/IIf interactions with endothelial cells increased the tyrosine phosphorylation of three cellular components with relative mass of 145,000, 125,000 and 70,000 in endothelial cells. These proteins were identified as phospholipase Cgamma (PLCy), focal adhesion kinase (FAK) and paxillin after immunoprecipitation with monoclonal antibodies (mAbs) and immunoblotting with antiphosphotyrosine mAbs. These results suggested that beta1 integrins could be one of the components implicated in the modulin activity of protein I/IIf. By incubating protein I/IIf with either purified alpha5beta1 integrins or with alpha5beta1 integrins overexpressing CHO cells, we demonstrated that alpha5beta1 integrins act as cell receptors for protein I/IIf. We also showed that protein I/IIf interactions with alpha5beta1 integrins lead to IL-8 secretion. Using specific inhibitors, we demonstrated that protein I/IIf-induced IL-8 release involves mitogen-activated protein kinases (MAPKs), and that PLCgamma and PKC also seem to contribute to protein I/IIf stimulation. However, PI-3K activation is not involved in IL-8 release. Altogether, these results indicate that, after binding to alpha5beta1 integrins, protein I/IIf induces IL-8 release by activating the MAPKs signalling pathways. PMID- 11207552 TI - New insights into the role of the cytoskeleton in phagocytosis of Entamoeba histolytica. AB - Entamoeba histolytica, a human parasite, crosses the natural barriers of the intestine and, in turn, spreads into the deeper organs, resulting in amoebiasis. The motility of the parasite and its ability to lyse or phagocytose human cells facilitates passage of the amoeba through the intestinal epithelium. Little is known about the uptake of material by this parasite; nevertheless, the cytoskeleton is believed to play a role in phagocytosis. Myosin IB, an actin binding protein, localizes to the phagocytic cup and, with time, surrounds the internalized phagosome itself. The role of unconventional myosins in phagocytosis has also been demonstrated in other cell types, suggesting that this molecular mechanism is a common denominator in phagocytic events. Here, we summarize the emerging view of the role of unconventional myosins as well as other cytoskeleton associated proteins in pseudopod formation at early stages of phagocytosis and during the late step of this process in E. histolytica. PMID- 11207553 TI - Phagocytic processing of antigens for presentation by class II major histocompatibility complex molecules. AB - Microbes and other particulate antigens (Ags) are internalized by phagocytosis and then reside in plasma membrane-derived phagosomes. The contribution of phagosomes to the degradation of Ags has long been appreciated. It has been unclear, however, whether peptides derived from these degraded antigens bind class II major histocompatibility complex (MHC-II) molecules within phagosomes or within endocytic compartments that receive Ag fragments from phagosomes. Recent experiments have demonstrated that phagosomes containing Ag-conjugated latex beads express a full complement of Ag-processing molecules, e.g. MHC-II molecules, invariant chain, H2-DM and proteases sufficient to degrade bead- associated Ag. These phagosomes mediate the formation of peptide-MHC-II complexes, which are transported to the cell surface and presented to T cells. Phagosomes acquire both newly synthesized and plasma membrane-derived MHC-II molecules, but the formation of peptide-MHC-II complexes in phagosomes primarily involves newly synthesized MHC-II molecules. The content and traffic of phagosomal proteins vary considerably with the type of Ag ingested. Pathogenic microbes can alter phagosome composition and function to reduce Ag processing. For example, Mycobacterium tuberculosis blocks the maturation of phagosomes and reduces the ability of infected cells to present exogenous soluble protein Ags. PMID- 11207554 TI - Fluorescence image analysis of the association between Porphyromonas gingivalis and gingival epithelial cells. AB - We have developed a fluorescence imaging technique using a DNA-binding dye to visualize, over time, the physical interactions between Porphyromonas gingivalis and human gingival epithelial cells in vitro. The results extend previous observations of P. gingivalis invasion of gingival epithelial cells based on indirect measurements. An intracellular location for P. gingivalis was established by optical sectioning of images in the z-plane. Kinetic analysis showed that P. gingivalis invasion of epithelial cells is a rapid and efficient process, reaching completion after 12 min. Imaging of infected monolayers revealed that over 90% of a population of gingival epithelial cells contained bacteria. Furthermore, only vital bacteria were capable of invasion, and intracellular bacteria congregated in the perinuclear region of the epithelial cells. P. gingivalis remained inside the epithelial cells over a 24 h period and induced rearrangement of the actin cytoskeleton along with alteration of the size and shape of the epithelial cells. These findings provide direct evidence that entry rates of P. gingivalis into gingival epithelial cells are high and rapid, and that internalized bacteria initially localize in a specific region of the epithelial cells. PMID- 11207555 TI - Secretion of micronemal proteins is associated with toxoplasma invasion of host cells. AB - Toxoplasma gondii is an obligate intracellular parasite that actively invades a wide variety of vertebrate cells, although the basis of its pervasive cell invasion is not completely understood. Here, we demonstrate, using several independent assays, that Toxoplasma invasion of host cells is tightly coupled to the release of proteins stored within apical secretory granules called micronemes. Both microneme secretion and cell invasion were highly temperature dependent, and partial depletion of microneme resulted in a transient loss of infectivity. Chelation of parasite intracellular calcium strongly inhibited both microneme release and invasion of host cells, and this effect was partially reversed by raising intracellular calcium using the ionophore A23187. We also provide evidence that a staurosporine-sensitive kinase activity regulates microneme discharge and is required for parasite invasion of host cells. Additionally, we demonstrate that, during apical attachment to the host cell, the micronemal protein MIC2 is released at the junction between the parasite and the host cell. During invasion, MIC2 is successively translocated towards the posterior end of the parasite and is shed before entry of the parasite into the vacuole. Furthermore, we show that the full-length cellular form of MIC2, but not the proteolytically modified secreted form of MIC2, binds specifically to host cells. Collectively, these observations strongly imply that micronemal proteins play a role in Toxoplasma invasion of host cells. PMID- 11207556 TI - Characterization and intracellular trafficking pattern of vacuoles containing Chlamydia pneumoniae in human epithelial cells. AB - Chlamydiae are obligate intracellular pathogens that reside within a membrane bound vacuole throughout their developmental cycle. In this study, the intraphagosomal pH of Chlamydia pneumoniae (Cpn) was qualitatively assessed, and the intracellular fate of the pathogen-containing vacuole and its interaction with endocytic organelles in human epithelial cells were analysed using conventional immunofluorescence and confocal microscopy. The pH-sensitive probes acridine orange (AO), LysoTracker (LyT) and DAMP did not accumulate in the bacterial inclusion. In addition, exposure of cells to bafilomycin A1(BafA1), a potent acidification inhibitor, did not inhibit or delay chlamydial growth. The chlamydial compartment was not accessible to the fluid-phase tracer Texas Red (TR)-dextran and did not exhibit any level of staining for the late endosomal marker cation-independent mannose-6-phosphate receptor (Ci-M6PR) or for the lysosomal-associated membrane proteins (LAMP-1 and -2) and CD63. In addition, transferrin receptor (TfR)-enriched vesicles were observed close to Cpn vacuoles, potentially indicating a specific translocation of these organelles through the cytoplasm to the vicinity of the vacuole. We conclude that Cpn, like other chlamydial spp., circumvents the host endocytic pathway and inhabits a non-acidic vacuole, which is dissociated from late endosomes and lysosomes, but selectively accumulates early endosomes. PMID- 11207557 TI - Stability of the Listeria monocytogenes ActA protein in mammalian cells is regulated by the N-end rule pathway. AB - Upon infection of mammalian cells, Listeria monocytogenes lyses the phagosome and enters the cytosol, where it secretes proteins necessary for its intracellular growth cycle. Consequently, bacterial proteins exposed to the cytosol are potential targets for degradation by host cytosolic proteases. One pathway for degradation of host cytosolic proteins, the N-end rule pathway, involves recognition of the N-terminal amino acid and is mediated by the proteasome. However, very few natural N-end rule substrates have been identified. We have examined the L. monocytogenes ActA protein as a potential target for this pathway. ActA is an essential determinant of L. monocytogenes pathogenesis that is required to induce actin-based motility and cell-to-cell spread. We show that the half-life of a secreted form of ActA can be altered in the mammalian cytosol by changing the N-terminal amino acid. Moreover, the introduction of a destabilizing N-terminus into the functional, surface-bound form of ActA results in a small-plaque phenotype in L2 cells, which is partially reversible by an inhibitor of the proteasome. These results indicate that the L. monocytogenes ActA protein is a natural N-end rule substrate, and that optimal function of ActA in mediating cell-to-cell spread is dependent upon its intracellular turnover rate. PMID- 11207558 TI - Enteropathogenic Escherichia coli (EPEC) attachment to epithelial cells: exploiting the host cell cytoskeleton from the outside. AB - Enteropathogenic Escherichia coli (EPEC), a leading cause of human infantile diarrhoea, is the prototype for a family of intestinal bacterial pathogens that induce attaching and effacing (A/E) lesions on host cells. A/E lesions are characterized by localized effacement of the brush border of enterocytes, intimate bacterial attachment and pedestal formation beneath the adherent bacteria. As a result of some recent breakthrough discoveries, EPEC has now emerged as a fascinating paradigm for the study of host-pathogen interactions and cytoskeletal rearrangements that occur at the host cell membrane. EPEC uses a type III secretion machinery to attach to epithelial cells, translocating its own receptor for intimate attachment, Tir, into the host cell, which then binds to intimin on the bacterial surface. Studies of EPEC-induced cytoskeletal rearrangements have begun to provide clues as to the mechanisms used by this pathogen to subvert the host cell cytoskeleton and signalling pathways. These findings have unravelled new ways by which pathogenic bacteria exploit host processes from the cell surface and have shed new light on how EPEC might cause diarrhoea. PMID- 11207559 TI - Distinct effects of Vibrio cholerae haemagglutinin/protease on the structure and localization of the tight junction-associated proteins occludin and ZO-1. AB - Vibrio cholerae produces a little-studied cytotoxin, haemagglutinin/protease (HA/P), in addition to several better-characterized enterotoxins, i.e. cholera toxin (CT), zonula occludens toxin (ZOT) and accessory cholera enterotoxin (Ace). We have found recently that HA/P perturbs the barrier function of Mardin-Darby canine kidney epithelial cell line I (MDCK-I) by affecting the intercellular tight junctions (TJs) and the F-actin cytoskeleton. In the present study we have assessed more specifically how TJs are affected by HA/P by investigating the cellular localization and biochemical integrity of two well-characterized TJ associated proteins, occludin and ZO-1. Western blot analysis showed that occludin bands of 66-85 kDa were digested by HA/P to two predominant bands of around 50 kDa and 35 kDa, and that this degradation was greatly attenuated when the specific bacterial metalloproteinase inhibitor Zincov was co-administered. Trypsin, on the other hand, did not degrade occludin when it was applied in the same way, suggesting that the degradation of occludin by HA/P is an early and specific event. The other TJ-associated protein ZO-1 was not degraded by HA/P in parallel experiments, suggesting the selectivity of HA/P-associated protein degradation. Moreover, immunofluorescence labelling and confocal microscopy showed that ZO-1, but not occludin, around cell-cell boundaries was rearranged by HA/P treatment. Since ZO-1 is located on the inside of the plasma membrane and is directly associated with occludin, the results indicate that breakdown of occludin may send signals to ZO-1 that affect its organization and the structure of the F-actin cytoskeleton. Our finding that the zinc-containing metalloprotease of V. cholerae specifically degraded occludin suggests that specific degradation of important host proteins by bacterial zinc-containing metalloproteases may be an important mechanism in microbial pathogenesis. PMID- 11207560 TI - CD44 binds to the Shigella IpaB protein and participates in bacterial invasion of epithelial cells. AB - Shigella entry into epithelial cells is characterized by a transient reorganization of the host cell cytoskeleton at the site of bacterial interaction with the cell membrane, which leads to bacterial engulfment in a macropinocytic process. Using affinity chromatography on HeLa cell extracts, we show here that the hyaluronan receptor CD44 associates with IpaB, a Shigella protein that is secreted upon cell contact. Overlay and solid-phase assays indicated that IpaB binds directly to the extracellular domain of CD44; binding is saturable and inhibitable, with a half-maximal inhibitory concentration of 175 nM. Immunoprecipitation experiments showed that IpaB associates with CD44 during Shigella entry. CD44 is recruited at bacterial entry sites and localizes at the plasma membrane of cellular extensions induced by Shigella. Pretreatment of cells with an anti-CD44 monoclonal antibody resulted in inhibition of Shigella-induced cytoskeletal reorganization, as well as inhibition of bacterial entry, whereas transfection of CD44 in cells that are deficient for CD44 results in increased bacterial binding to cells and internalization. The IpaB-CD44 interaction appears to be required for Shigella invasion by initiating the early steps of the entry process. PMID- 11207561 TI - A secondary structure motif predictive of protein localization to the chlamydial inclusion membrane. AB - Chlamydiae are obligate intracellular pathogens that spend their entire growth phase sequestered in a membrane-bound vacuole called an inclusion. A set of chlamydial proteins, labelled Inc proteins, has been identified in the inclusion membrane (IM). The predicted IncA, IncB and IncC amino acid sequences share very limited similarity, but a common hydrophobicity motif is present within each Inc protein. In an effort to identify a relatively complete catalogue of Chlamydia trachomatis proteins present in the IM of infected cells, we have screened the genome for open reading frames encoding this structural motif. Hydropathy plot analysis was used to screen each translated open reading frame in the C. trachomatis genome database. Forty-six candidate IM proteins (C-lncs) that satisfied the criteria of containing a bilobed hydrophobic domain of at least 50 amino acids were identified. The genome of Chlamydia pneumoniae encodes a larger collection of C-lnc proteins, and only approximately half of the C-lncs are encoded within both genomes. In order to confirm the hydropathy plot screening method as a valid predictor of C-lncs, antisera and/or monoclonal antibodies were prepared against six of the C. trachomatis C-lncs. Immunofluorescence microscopy of C. trachomatis-infected cells probed with these antibodies showed that five out of six C-lncs are present in the chlamydial IM. Antisera were also produced against C. pneumoniae p186, a protein sharing identity with Chlamydia psittaci lncA and carrying a similar bilobed hydrophobic domain. These antisera labelled the inclusion membrane in C. pneumoniae infected cells, confirming that proteins sharing the unique secondary structural characteristic also localize to the inclusion membrane of C. pneumoniae. Sera from patients with high-titre antibodies to C. trachomatis were examined for reactivity with each tested C-lnc protein. Three out of six tested C-lncs were recognized by a majority of these patient sera. Collectively, these studies identify and characterize novel proteins localized to the chlamydial IM and demonstrate the existence of a potential secondary structural targeting motif for localization of chlamydial proteins to this unique intracellular environment. PMID- 11207562 TI - The Salmonella virulence plasmid spv genes are required for cytopathology in human monocyte-derived macrophages. AB - The pathogenesis of serious systemic Salmonella infections is characterized by survival and proliferation of bacteria inside macrophages. Infection of human monocyte-derived macrophages in vitro with S. typhimurium or S. dublin produces cytopathology characterized by detachment of cells that contain large numbers of proliferating bacteria. This cytopathology is dependent on the expression of the bacterial spv genes, a virulence locus previously shown to markedly enhance the ability of Salmonella to produce systemic disease. After 24 h of infection, macrophage cultures contain two populations of bacteria: (i) proliferating organisms present in a detached cell fraction; and (ii) a static bacterial population in macrophages remaining attached to the culture well. Mutations in either the essential transcriptional activator SpvR or the key SpvB protein markedly reduce the cytopathic effect of Salmonella infection. The spv-dependent cytopathology in macrophages exhibits characteristics of apoptosis, with release of nucleosomes into the cytoplasm, nuclear condensation and DNA fragmentation. The current findings suggest that the mechanism of the spv effect is through induction of increased cytopathology in host macrophages. PMID- 11207563 TI - A recombinant Salmonella typhimurium vaccine strain is taken up and survives within murine Peyer's patch dendritic cells. AB - The attenuated Salmonella typhimurium PhoPc strain is avirulent but immunogenic via the oral route in mice and is attenuated in survival in macrophage cell lines. In this study, the fate of PhoPc bacteria expressing green fluorescent protein was investigated in murine Peyer's patches. The survival of PhoPc was monitored after orogastric inoculation of BALB/c mice. Bacteria persisted for several weeks in the Peyer's patches and were also recovered from the mesenteric lymph nodes and spleen. Confocal microscopy analysis identified dendritic cells as the Peyer's patch cell type that internalized PhoPc expressing green fluorescent protein at early time points. In addition, live PhoPc were found in Peyer's patch dendritic cells and not in B cells 3 days after orogastric inoculation. Taken together, these results provide strong evidence that PhoPc is internalized and survives within Peyer's patch dendritic cells. As these cells are potent antigen-presenting cells, these data could explain the immunogenicity of S. typhimurium vaccine strains in vivo. PMID- 11207564 TI - Syndecan-1 and syndecan-4 can mediate the invasion of OpaHSPG-expressing Neisseria gonorrhoeae into epithelial cells. AB - Neisseria gonorrhoeae (Ngo) expressing the outer membrane protein OpaHSPG can adhere to and invade epithelial cells via binding to heparan sulphate proteoglycan (HSPG) receptors. In this study, we have investigated the role of syndecan-1 and syndecan-4, two members of the HSPG family, in the uptake of Ngo by epithelial cells. When overexpressed in HeLa cells, both syndecans co-localize with adherent Ngo on the host cell surface. This overexpression of syndecan-1 and syndecan-4 leads to a three- and sevenfold increase in Ngo invasion respectively. In contrast, transfection with the syndecan-1 and syndecan-4 mutant constructs lacking the intracellular domain results in an abrogation of the invasion process, characteristic of a dominant-negative mode of action. A concomitant loss of the capacity to mediate Ngo uptake was also observed with syndecan-4 mutant constructs carrying lesions in the dimerization motif necessary for the binding of protein kinase C (PKC) and phosphatidylinositol 4,5-bisphosphate (PIP2), and mutants that are deficient in a C-terminal EFYA amino acid motif responsible for binding to syntenin or CASK. We conclude that syndecan-1 and syndecan-4 can both mediate Ngo uptake into epithelial cells, and that their intracellular domains play a crucial role in this process, perhaps by mediating signal transduction or anchorage to the cytoskeleton. PMID- 11207565 TI - Cross-talk between enteric pathogens and the intestine. AB - Enteric pathogens finely regulate the expression of virulence genes in reply to stimuli generated by the intestinal environment. This minireview focuses on recently discovered strategies developed by enteric bacteria to cause intestinal secretion through the elaboration of factors that share structure and function with specific host counterparts. Such bacterial antigens appear to interfere largely with the epithelial cell signalling that physiologically regulates the numerous and, as yet not fully elucidated, mechanisms controlling both the transcellular and the paracellular secretion pathways. Heat-stable enterotoxins (STs) elaborated by enterotoxigenic Escherichia coli and the enteroaggregative E. coli enterotoxin (EAST1) are both typical examples of enteric toxins that activate the transcellular secretion pathway by mimicking guanylin, the endogenous modulator of cGMP signalling. Alternative strategies have been developed by Salmonella to induce intestinal secretion through the elaboration of a factor (SopB) that resembles at least two of the host cell 4-phosphatases, enzymes that activate the Ca-dependent transcellular secretion pathway. Finally, Vibrio cholerae has developed innovative tactics to activate the paracellular secretion pathway through the elaboration of Zonula occludens toxin (Zot), a factor that mimics a recently described physiological modulator of intercellular tight junctions. PMID- 11207566 TI - Theileria parva: taking control of host cell proliferation and survival mechanisms. AB - The intracellular parasite Theileria parva infects and transforms bovine T-cells, inducing their uncontrolled proliferation and spread in non-lymphoid as well as lymphoid tissues. This parasite-induced transformation is the predominant factor contributing to the pathogenesis of a lymphoproliferative disease, called East Coast fever. T. parva-transformed cells become independent of antigenic stimulation or exogenous growth factors. A dissection of the signalling pathways that are activated in T. parva-infected cells shows that the parasite bypasses signalling pathways that normally emanate from the T-cell antigen receptor to induce continuous proliferation. This review concentrates on the influence of the parasite on the state of activation of the mitogen-activated protein kinase (MAPK), NF-kappaB and phosphoinositide-3-kinase (PI3-K) pathways in the host cell. Of the MAPKs, JNK, but not ERK or p38, is active, inducing constitutive activation of the transcription factors AP-1 and ATF-2. A crucial step in the transformation process is the persistent activation of the transcription factor NF-kappaB, which protects T. parva-transformed cells from spontaneous apoptosis accompanying the transformation process. Inhibitor studies also suggest an important role for the lipid kinase, PI-3K, in the continuous proliferation of T. parva-transformed lymphocytes. PMID- 11207567 TI - LaXp180, a mammalian ActA-binding protein, identified with the yeast two-hybrid system, co-localizes with intracellular Listeria monocytogenes. AB - The Listeria monocytogenes surface protein ActA is an important virulence factor required for listerial intracellular movement by inducing actin polymerization. The only host cell protein known that directly interacts with ActA is the phosphoprotein VASP, which binds to the central proline-rich repeat region of ActA. To identify additional ActA-binding proteins, we applied the yeast two hybrid system to search for mouse proteins that interact with ActA. A mouse cDNA library was screened for ActA-interacting proteins (AIPs) using ActA from strain L. monocytogenes EGD as bait. Three different AIPs were identified, one of which was identical to the human protein LaXp180 (also called CC1). Binding of LaXp180 to ActA was also demonstrated in vitro using recombinant histidine-tagged LaXp180 and recombinant ActA. Using an anti-LaXp180 antibody and fluorescence microscopy, we showed that LaXp180 co-localizes with a subset of intracellular, ActA expressing L. monocytogenes but was never detected on intracellularly growing but ActA-deficient mutants. Furthermore, LaXp180 binding to intracellular L. monocytogenes was asymmetrical and mutually exclusive with F-actin polymerization on the bacterial surface. LaXp180 is a putative binding partner of stathmin, a protein involved in signal transduction pathways and in the regulation of microtubule dynamics. Using immunofluorescence, we showed that stathmin co localizes with intracellular ActA-expressing L. monocytogenes. PMID- 11207568 TI - Leishmania promastigotes require lipophosphoglycan to actively modulate the fusion properties of phagosomes at an early step of phagocytosis. AB - The lipophosphoglycan (LPG) of Leishmania promastigotes plays key roles in parasite survival in both insect and mammalian hosts. Evidence suggests that LPG decreases phagosome fusion properties at the onset of infection in macrophages. The mechanisms of action of this molecule are, however, poorly understood. In the present study, we used a panoply of Leishmania mutants displaying modified LPG structures to determine more precisely how LPG modulates phagosome-endosome fusion. Using an in vivo fusion assay measuring, at the electron microscope, the transfer of solute materials from endosomes to phagosomes, we provided further evidence that the repeating Gal(beta1,4)Man(alpha1-PO4) units of LPG are responsible for the alteration in phagosome fusion. The inhibitory effect of LPG on phagosome fusion was shown to be more potent towards late endocytic organelles and lysosomes than early endosomes, explaining how Leishmania promastigotes can avoid degradation in hydrolase-enriched compartments. The involvement of other repeating unit-containing molecules, including the secreted acid phosphatase, in the inhibition process was ruled out, as an LPG-defective mutant (Ipg1-) which secretes repeating unit-containing glycoconjugates was present in highly fusogenic phagosomes. In L. major, oligosaccharide side-chains of LPG did not contribute to the inhibition process, as Spock, an L. major mutant lacking LPG side-chains, blocked fusion to the same extent as wild-type parasites. Finally, dead parasites internalized from the culture medium were not as efficient as live parasites in altering phagosome-endosome fusion, despite the presence of LPG. However, the killing of parasites with vital dyes after their sequestration in phagosomes had no effect on the fusion properties of this organelle. Collectively, these results suggest that living promastigotes displaying full length cell surface LPG can actively influence macrophages at an early stage of phagocytosis to generate phagosomes with poor fusogenic properties. PMID- 11207569 TI - A novel function of InIB from Listeria monocytogenes: activation of NF-kappaB in J774 macrophages. AB - Listeria monocytogenes causes a pro-inflammatory response on adhesion to macrophages. Upregulation of inflammation genes involves the transcription factor NF-kappaB. Several components of L. monocytogenes, including lipoteichoic acid (LTA), phospholipases and listeriolysin O (LLO), have since been shown to mediate NF-kappaB activation. Here, we report that purified recombinant InlB, but not internalin (InlA), is a potent activator of NF-kappaB in the mouse macrophage like cell line J774. Expression of InlB in Listeria innocua enhances its ability to activate NF-kappaB, while deletion of InlB from L. monocytogenes marginally decreases its effect on NF-kappaB, possibly because of the presence of NF-kappaB activators such as LTA and LLO. The effect correlates with the rapid degradation of IkappaBalpha, a sustained degradation of IkappaBbeta and increases in tumour necrosis factor alpha (TNF-alpha) and interleukin (IL) 6 production, two cytokines controlled by NF-kappaB. Using a series of anti-InlB monoclonal antibodies and domains of InlB, NF-kappaB activation was shown to be dependent upon the N-terminal 213-amino-acid leucine-rich repeat (LRR) domain of InlB, recently demonstrated to be responsible for InlB-mediated L. monocytogenes invasion and phosphoinositide-3 (PI-3) kinase activation. The effect of InlB was blocked by PI-3 kinase inhibitors, indicating the involvement of PI-3 kinase in this response. This report thus illustrates that InlB not only promotes invasion, but also contributes to the macrophage pro-inflammatory response. PMID- 11207570 TI - Chlamydia-dependent biosynthesis of a heparan sulphate-like compound in eukaryotic cells. AB - One hypothesis for the mechanism of chlamydial interaction with its eukaryotic host cell invokes a trimolecular mechanism, whereby a Chlamydia-derived glycosaminoglycan bridges a chlamydial acceptor molecule and a host receptor enabling attachment and invasion. We show that a heparan sulphate-specific monoclonal antibody specifically binds a glycosa-minoglycan localized to the surface of the chlamydial organism and effectively neutralizes infectivity of both C. trachomatis and C. pneumoniae. In addition to the ability of this antibody to neutralize infectivity, direct visualization using immunofluorescence demonstrated staining of chlamydial organisms localized to the intracellular vacuole. The chlamydial-associated glycosaminoglycan was specifically labelled with [14C]-glucosamine, and the labelled compound was immunoprecipitated and resolved by gel electrophoresis. The chlamydial-associated glycosaminoglycan is a high-molecular-weight compound similar in size to heparin or heparan sulphate and was sensitive to cleavage by heparan sulphate lyase. These data demonstrate that a glucosamine-containing sulphated polysaccharide is produced within the intracellular vacuole containing chlamydiae and is a target for antibody-mediated neutralization of infectivity. PMID- 11207571 TI - Two distinct pathways for the invasion of Streptococcus pyogenes in non phagocytic cells. AB - Adherence to and invasion of epithelial cells represent important pathogenic mechanisms of Streptococcus pyogenes. A fibronectin-binding surface protein of S. pyogenes, Sfbl protein, has been implicated in both adherence and invasion processes. Invasion of Sfbl-containing strains has been suspected to be responsible for the failure of antibiotics treatment to eradicate S. pyogenes. In this study, we tested the adherence and invasion properties of two well characterized clinical isolates: A40, which expresses Sfbl; and A8, which is Sfbl negative and is unable to bind fibronectin. In strain A40, Sfbl was the main factor required for attachment and invasion by using fibronectin as a bridging molecule and the alpha5beta1 integrin as cellular receptor. The uptake process was characterized by the generation of large membrane invaginations at the bacteria-cell interface without evidence of actin recruitment or cellular injury. A40 cells were located in phagosomes and, only 24 h after infection, a consistent part of the bacterial population reached the cytoplasm. In contrast, uptake of strain A8 required major rearrangements of cytoskeletal proteins underneath attached bacteria. In A8, a proteinaceous moiety was involved, which does not interact with alpha5beta1 or need any known bridging molecule. Bacterial attachment stimulated elongation and massive recruitment of neighbouring microvilli, which fused to surround streptococcal chains. They led to the generation of large pseudopod-like structures, which engulfed bacteria that were rapidly released and replicated in the cytoplasm. The identification of two completely different uptake pathways reported here provided further evidence regarding the diversity of S. pyogenes isolates and might contribute towards understanding the pathogenesis and persistence of S. pyogenes. PMID- 11207573 TI - Dictyostelium discoideum: a new host model system for intracellular pathogens of the genus Legionella. AB - The soil amoeba Dictyostelium discoideum is a haploid eukaryote that, upon starvation, aggregates and enters a developmental cycle to produce fruiting bodies. In this study, we infected single-cell stages of D. discoideum with different Legionella species. Intracellular growth of Legionella in this new host system was compared with their growth in the natural host Acanthamoeba castellanii. Transmission electron microscopy of infected D. discoideum cells revealed that legionellae reside within the phagosome. Using confocal microscopy, it was observed that replicating, intracellular, green fluorescent protein (GFP) tagged legionellae rarely co-localized with fluorescent antibodies directed against the lysosomal protein DdLIMP of D. discoideum. This indicates that the bacteria inhibit the fusion of phagosomes and lysosomes in this particular host system. In addition, Legionella infection of D. discoideum inhibited the differentiation of the host into the multicellular fruiting stage. Co-culture studies with profilin-minus D. discoideum mutants and Legionella resulted in higher rates of infection when compared with infections of wild-type amoebae. Because the amoebae are amenable to genetic manipulation as a result of their haploid genome and because a number of cellular markers are available, we show for the first time that D. discoideum is a valuable model system for studying intracellular pathogenesis of microbial pathogens. PMID- 11207572 TI - Translocation of the Helicobacter pylori CagA protein in gastric epithelial cells by a type IV secretion apparatus. AB - Helicobacter pylori is one of the most common bacterial pathogens, infecting about 50% of the world population. The presence of a pathogenicity island (PAI) in H. pylori has been associated with gastric disease. We present evidence that the H. pylori protein encoded by the cytotoxin-associated gene A (cagA) is translocated and phosphorylated in infected epithelial cells. Two-dimensional gel electrophoresis (2-DE) of proteins isolated from infected AGS cells revealed H. pylori strain-specific and time-dependent tyrosine phosphorylation and dephosphorylation of several 125-135 kDa and 75-80 kDa proteins. Immunoblotting studies, matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS), cell fractionation and confocal microscopy demonstrated that one of the 125 135 kDa proteins represents the H. pylori CagA protein, which is translocated into the host cell membrane and the cytoplasm. Translocation of CagA was dependent on functional cagA gene and virulence (vir) genes of a type IV secretion apparatus composed of virB4, virB7, virB10, virB11 and virD4 encoded in the cag PAI of H. pylori. Our findings support the view that H. pylori actively translocates virulence determinants, including CagA, which could be involved in the development of a variety of gastric disease. PMID- 11207574 TI - Translocation of Yersinia entrocolitica across reconstituted intestinal epithelial monolayers is triggered by Yersinia invasin binding to beta1 integrins apically expressed on M-like cells. AB - Yersinia enterocolitica cross the intestinal epithelium via translocation through M cells, which are located in the follicle-associated epithelium (FAE) of Peyer's patches (PP). To investigate the molecular basis of this process, studies were performed using a recently developed in vitro model, in which the enterocyte-like cell line Caco-2 and PP lymphocytes are co-cultured in order to establish FAE like structures including M cells. Here, we demonstrate that Y. enterocolitica does not adhere significantly to the apical membrane of differentiated enterocyte like Caco-2 cells that express binding sites for Ulex europaeus agglutinin (UEA) 1. In contrast, Y. enterocolitica adhered to, and was internalized by, cells that lacked UEA-1 binding sites and displayed a disorganized brush border. These cells were considered to be converted to M-like cells. Further analysis revealed that part of these cells expressed beta1 integrins at their apical surface and, as revealed by comparison of wild-type and mutant strains, interacted with invasin of Y. enterocolitica. Consistently, anti-beta1 integrin antibodies significantly inhibited internalization of inv-expressing yersiniae. Experiments with Yersinia mutant strains deficient in YadA or Yop secretion revealed that these virulence factors play a minor role in this process. After internalization, yersiniae were transported within LAMP-1-negative vacuoles to, and released at, the basal surface. Internalization and transport of yersiniae was inhibited by cytochalasin D, suggesting that F-actin assembly is required for this process. These results provide direct evidence that expression of beta1 integrins at the apical surface of M cells enables interaction with the invasin of Y. enterocolitica, and thereby initiates internalization and translocation of bacteria. PMID- 11207575 TI - Bacterial signals and cell responses during Shigella entry into epithelial cells. AB - Shigella invades epithelial cells by inducing cytoskeletal reorganization localized at the site of bacterial-host cell interaction. During entry, the Shigella type III secretion apparatus allows the insertion of a pore that contains the IpaB and IpaC proteins into cell membranes. Insertion of this complex is thought to allow translocation of the carboxy-terminus moiety of IpaC, but also of other Shigella effectors, such as IpaA, into the cell cytosol. IpaC triggers actin polymerization and the formation of filopodial and lamellipodial extensions dependent on the Cdc42 and Rac GTPases. IpaA, on the other hand, binds to the focal adhesion protein vinculin and induces depolymerization of actin filaments. IpaA and the GTPase Rho are not required for actin polymerization at the site of bacterial contact with the cell membrane, but allow the transformation of the IpaC-induced extensions into a structure that is productive for bacterial entry. Rho is required for the recruitment at entry foci of ezrin, a cytoskeletal linker required for Shigella entry, and also of the Src tyrosine kinase. The Src tyrosine kinase activity, which is required for Shigella-induced actin polymerization, also appears to be involved in a negative regulatory loop that downregulates Rho at the site of entry. PMID- 11207576 TI - Actin-based motility of pathogens: the Arp2/3 complex is a central player. AB - Bacterial actin-based motility has provided cell biologists with tools that led to the recent discovery that, in many forms of actin-based motilities, a key player is a protein complex named the Arp2/3 complex. The Arp2/3 complex is evolutionally conserved and made up of seven polypeptides involved in both actin filament nucleation and organization. Interestingly, this complex is inactive by itself and recent work has highlighted the fact that its activation is achieved differently in the different types of actin-based motilities, including the well known examples of Listeria and Shigella motilities. Proteins of the WASP family and small G-proteins are involved in most cases. It is interesting that bacteria bypass or mimic some of the events occurring in eukaryotic systems. The Shigella protein IcsA recruits N-WASP and activates it in a Cdc42-like fashion. This activation leads to Arp2/3 complex recruitment, activation of the complex and ultimately actin polymerization and movement. The Listeria ActA protein activates Arp2/3 directly and, thus, seems to mimic proteins of the WASP family. A breakthrough in the field is the recent reconstitution of the actin-based motilities of Listeria and N-WASP-coated E. coli (IcsA) using a restricted number of purified cellular proteins including F-actin, the Arp2/3 complex, actin depolymerizing factor (ADF or cofilin) and capping protein. The movement was more effective upon addition of profilin, alpha-actinin and VASP (for Listeria). Bacterial actin-based motility is now one of the best-documented examples of the exploitation of mammalian cell machineries by bacterial pathogens. PMID- 11207577 TI - Alteration of epithelial cell transferrin-iron homeostasis by Neisseria meningitidis and Neisseria gonorrhoeae. AB - Iron is an essential element for nearly all organisms. In mammals, iron is transported to body tissues by the serum glycoprotein transferrin. Transferrin iron is internalized by binding to specific receptors followed by endocytosis. In vitro, Neisseria meningitidis and Neisseria gonorrhoeae can use iron from a variety of iron-containing compounds, including human transferrin. In vivo, transferrin is an important source of iron for N. gonorrhoeae: a mutant that is unable to bind and use transferrin-iron is unable to colonize the urethra of men or initiate disease at this site. As pathogenic Neisseria and its human host derive much of their iron from transferrin, we reasoned that a competition may exist between microbe and host epithelial cells for transferrin-iron at certain stages of infection. We therefore tested the hypothesis that N. meningitidis and N. gonorrhoeae may actively interfere with host transferrin-iron metabolism. We report that Neisseria-infected human epithelial cells have reduced levels of transferrin receptor messenger RNA and cycling transferrin receptors. The ability of infected cells to internalize transferrin receptor is also reduced. Finally, the relative distribution of surface and cycling transferrin receptors is altered in an infected cell. We conclude that Neisseria infection alters epithelial cell transferrin-iron homeostasis at multiple levels. PMID- 11207578 TI - Integrin beta1-chain residues involved in substrate recognition and specificity of binding to invasin. AB - A highly conserved 14-amino-acid region of the chicken beta1 integrin chain (beta1chk residues 151-168) hypothesized to be involved in divalent cation coordination was analysed to determine whether invasin uses the same structural determinants as fibronectin (Fn) to recognize receptors. For the most part, both proteins required similar beta1 chain residues for integrin recognition, although the relative preference of the integrin for the two substrates could be inverted mutationally. Substitution mutations in the amino terminal residues of this region resulted in defective binding to both substrates by the receptor, while substitutions at the carboxyl-terminal end of this region were better tolerated. A derivative carrying the double substitution (KDD160RDV) had the unique phenotype of maintaining Fn binding while abolishing invasin binding, indicating that this region of the receptor may determine substrate specificity. These data indicate that the integrin beta1 chain possesses a ligand binding site shared by invasin and Fn that can be altered by mutation to allow greater preference for the normally lower affinity substrate Fn than for invasin. It was also established that the region analysed has the ability to bind divalent cations. PMID- 11207579 TI - The bacterial protein YopJ abrogates multiple signal transduction pathways that converge on the transcription factor CREB. AB - Bacterially encoded proteins are known to affect eukaryotic signalling pathways and thus cell growth and differentiation. The enteric pathogen Yersinia pseudotuberculosis (YP) can translocate Yersinia outer proteins (Yops) into eukaryotic cells. Recently, MKK proteins have been identified as tentative targets of YopJ-mediated inhibition of ligand receptor-dependent signal transduction in mammalian cells. These results prompted us to assess whether multiple signal transduction pathways and their downstream target genes would also be subject to regulation by YopJ. Here, we show that YopJ effectively blocks the lipopolysaccharide (LPS) receptor, the interleukin (IL)-1beta receptor and the UVC-induced activation of the transcription receptor cAMP response element binding protein (CREB). In addition, by abrogating the phosphorylation of CREB and thus activating protein (AP)-1-dependent transcription, YopJ can block LPS induced clonal expansion that is associated with an adaptive immune response. Thus, YopJ interferes with multiple pathways converging on the transcription factor CREB. Our data are discussed in the context of YopJ acting as an antagonist to circumvent innate and adaptive immune responses at multiple levels. PMID- 11207580 TI - Salmonella typhimurium mutants that downregulate phagocyte nitric oxide production. AB - To examine the potential and strategies of the facultative intracellular pathogen Salmonella typhimurium to increase its fitness in host cells, we applied a selection that enriches for mutants with increased bacterial growth yields in murine J774-A.1 macrophage-like cells. The selection, which was based on intracellular growth competition, rapidly yielded isolates that out-competed the wild-type strain during intracellular growth. J774-A.1 cells responded to challenge with S. typhimurium by mounting an inducible nitric oxide synthase (iNOS) mRNA and protein expression and a concomitant nitric oxide (NO) production. Inhibition of NO production with the use of the competitive inhibitor N-monomethyl-L-arginine (NMMA) resulted in a 20-fold increase in bacterial growth yield, suggesting that the NO response prevented bacterial intracellular growth. In accordance with this observation, five out of the nine growth advantage mutants isolated inhibited production of NO from J774-A.1 cells, despite an induction of iNOS mRNA and iNOS protein. Accompanying bacterial phenotypes included alterations in lipopolysaccharide structure and in the profiles of proteins secreted by invasion-competent bacteria. The results indicate that S. typhimurium has the ability to mutate in several different ways to increase its host fitness and that inhibition of iNOS activity may be a major adaptation. PMID- 11207581 TI - Proteolytic activation of receptor-bound anthrax protective antigen on macrophages promotes its internalization. AB - Immunofluorescence and other methods have been used to probe the self-assembly and internalization of the binary toxin, anthrax lethal toxin (LeTx), in primary murine macrophages. Proteolytic activation of protective antigen (PA; 83 kDa, the B moiety of the toxin) by furin was the rate-limiting step in internalization of LeTx and promoted clearance of PA from the cell surface. A furin-resistant form of PA remained at the cell surface for at least 90 min. Oligomerization of receptor-bound PA63, the 63 kDa active fragment of PA, was manifested by its conversion to a pronase-resistant state, characteristic of the heptameric prepore form in solution. That oligomerization of PA63 triggers toxin internalization is supported by the observation that PA20, the complementary 20 kDa fragment of PA, inhibited clearance of nicked PA. The PA63 prepore, with or without lethal factor (LF), cleared slowly from the cell surface. These studies show that proteolytic cleavage of PA, in addition to permitting oligomerization and LF binding, also promotes internalization of the protein. The relatively long period of activation and internalization of PA at the cell surface may reflect adaptation of this binary toxin that maximizes self-assembly. PMID- 11207582 TI - Translocation of Bacillus anthracis lethal and oedema factors across endosome membranes. AB - The two exotoxins of Bacillus anthracis, the causative agent of anthrax, are the oedema toxin (PA-EF) and the lethal toxin (PA-LF). They exert their catalytic activities within the cytosol. The internalization process requires receptor mediated endocytosis and passage through acidic vesicles. We investigated the translocation of EF and LF enzymatic moieties across the target cell membrane. By selective permeabilization of the plasma membrane with Clostridium perfringens delta-toxin, we observed free full-size lethal factor (LF) within the cytosol, resulting from specific translocation from early endosomes. In contrast, oedema factor (EF) remained associated with the membranes of vesicles. PMID- 11207583 TI - Pathogen-induced apoptosis of macrophages: a common end for different pathogenic strategies. AB - Microbe-macrophage interactions play a central role in the pathogenesis of many infections. Several bacterial pathogens induce apoptosis specifically in macrophages, but the mechanisms by which it occurs differ, and the resulting pathology can take different courses. Macrophage death caused by Shigella flexneri and Salmonella spp. has been shown to result in the release of pro inflammatory cytokines. Conversely, Yersinia spp. induce apoptosis by suppressing the signalling pathways that lead to the production of tumour necrosis factor (TNF)-alpha, a cytokine essential for the control of this infection. It is likely that there are a variety of reasons why macrophages are particularly susceptible to pathogen-induced apoptosis. One reason may be the expression of surface receptors that recognize highly conserved bacterial components, such as lipopolysaccharide (LPS) and bacterial lipoproteins (BLPs). These receptors have recently been shown to activate pro-apoptotic signalling pathways. The roles of macrophage apoptosis in different disease processes are discussed. PMID- 11207584 TI - Intracellular survival by Chlamydia. AB - Chlamydiae are obligate intracellular bacterial pathogens whose entry into mucosal epithelial cells is required for intracellular survival and subsequent growth. After a seemingly stealthy entry, chlamydiae quickly modify their vacuole (i) for exit from the endosomal pathway to the exocytic pathway and (ii) to permit fusion with intercepted endoplasmic reticulum- and Golgi-derived vesicles carrying glycerophospholipids and sphingolipids for chlamydiae-containing vacuole membrane expansion. Chlamydiae possess novel hollow proteinaceous structures, termed projections, which they use to pierce the inclusion membrane, possibly to acquire from the epithelial cytoplasm nutrients they cannot synthesize; whether or not these truncated flagellar-like structures serve a dual exchange function for secretion of molecules to programme host cell signalling is unknown. Despite the accumulation of some 500-1000 progeny in the enormously enlarged inclusion, host cell function is surprisingly little disrupted, and progeny escape can be unobtrusive. This elegant adaptive pathogen strategy, which leads to silent, chronic human infection, is fascinating from a cellular microbiology perspective. PMID- 11207585 TI - Bacterial determinants of persistent throat colonization and the associated immune response in a primate model of human group A streptococcal pharyngeal infection. AB - Group A streptococcal (GAS) pharyngitis and the subsequent bacterial colonization of the human throat elicit an immune response that may precipitate acute rheumatic fever in a susceptible host. To study the bacterial determinants that influence throat colonization and induction of humoral immunity, we characterized the behavior of GAS strains in a baboon model. An M-type 3 clinical isolate of GAS typical of strains that cause pharyngitis and invasive infection was recovered from the pharynx of six out of six baboons for at least 6 weeks after oral inoculation. By contrast, an isogenic mutant deficient in M protein failed to colonize most animals or was rapidly cleared. An isogenic mutant deficient in hyaluronic acid capsule colonized five out of six animals, but only persisted in the pharynx for 14-21 days. Colonized animals developed serum antistreptolysin O (SLO) and anti-M protein immunoglobulin (Ig)G. The kinetics of the antibody responses were similar to those seen after human infection. Peak titres increased with the duration of throat carriage. Colonization with GAS prevented recurrent colonization after challenge with the homologous wild-type strain, but not after challenge with a strain of different M protein type. Early clearance of the M protein-deficient strain was associated with increased susceptibility of this strain to phagocytic killing in non-immune serum, whereas clearance of the acapsular strain was associated with increased susceptibility to phagocytic killing in the presence of specific antibody. These studies support critical and distinct effects of the GAS M protein and capsule on throat colonization and induction of humoral immunity in a model that reproduces important features of pharyngeal colonization and immune response following human infection. PMID- 11207586 TI - The secreted effector protein of Salmonella dublin, SopA, is translocated into eukaryotic cells and influences the induction of enteritis. AB - Salmonella-induced enteritis is associated with the induction of an acute intestinal inflammatory response and net fluid secretion into the lumen of infected mucosa. Proteins secreted by the Inv/Spa type III secretion system of Salmonella play a key role in the induction of these responses. We have demonstrated recently that the Inv/Spa-secreted SopB and SopD effector proteins are translocated into eukaryotic cells via a Sip-dependent pathway and act in concert to mediate inflammation and fluid secretion in infected ileal mucosa. Mutations of both sopB and sopD significantly reduced, but did not abrogate, the enteropathogenic phenotype. This indicated that other virulence factors are involved in the induction of enteritis. In this work, we characterize SopA, a secreted protein belonging to the family of Sop effectors of Salmonella dublin. We demonstrate that SopA is translocated into eukaryotic cells and provide evidence suggesting that SopA has a role in the induction of enteritis. PMID- 11207587 TI - Enteropathogenic Escherichia coli dephosphorylates and dissociates occludin from intestinal epithelial tight junctions. AB - Enteropathogenic Escherichia coli (EPEC) increases tight junction permeability in part by phosphorylating the 20 kDa myosin light chain (MLC20) that induces cytoskeletal contraction. The impact of this enteric pathogen on specific tight junction (TJ) proteins has not been investigated. We examined the effect of EPEC infection on occludin localization and phosphorylation in intestinal epithelial cells. After infection by EPEC, a progressive shift of occludin from a primarily TJ-associated domain to an intracellular compartment occurred, as demonstrated by immunofluorescent staining. A reverse in the ratio of phosphorylated to dephosphorylated occludin accompanied this morphological change. Eradication of EPEC with gentamicin resulted in the normalization of occludin localization and phosphorylation. The serine/threonine phosphatase inhibitor, calyculin A, prevented these events. The EPEC-associated decrease in transepithelial electrical resistance, a measure of TJ barrier function, returned to baseline after gentamicin treatment. Non-pathogenic E. coli, K-12, did not induce these changes. Transformation of K-12 with the pathogenicity island of EPEC, however, conferred the phenotype of wild-type EPEC. Deletion of specific EPEC genes encoding proteins involved in EPEC type III secretion markedly attenuated these effects. These findings suggest that EPEC-induced alterations in occludin contribute to the pathophysiology associated with this infection. PMID- 11207588 TI - Chlamydial infection of polarized HeLa cells induces PMN chemotaxis but the cytokine profile varies between disseminating and non-disseminating strains. AB - While genital infections caused by Chlamydia trachomatis are generally asymptomatic, the density and pattern of inflammation varies considerably. The purpose of this study was to try to dissect the signalling in chlamydiae-infected epithelial cells that triggers innate responses and regulates polymorphonuclear neutrophil (PMN) chemotaxis. Polarized endocervical epithelial HeLa cells, grown in commercial inserts, were inoculated either with the non-disseminating (luminal) serovar E or the disseminating serovar L2. At 12-48 h after infection, the chambers were used in a quantitative chemotaxis assay, and cytokine production by infected cells was examined using cDNA microarray technology and confirmed by enzyme-linked immunosorbent assay (ELISA). Infection of HeLa cells with C. trachomatis E or L2 induced a strong and similar PMN chemotactic response, but larger amounts of interleukin (IL)-8 and IL-11 were released after infection with serovar L2. IL-6 was also produced in modest amounts after infection with either strain, but no IL-1alpha or tumour necrosis factor (TNF) alpha was detected in any of the culture supernatants tested. IL-11 did not appear to influence the PMN response to chlamydial infection, but secretion of large amounts of this anti-inflammatory cytokine, mainly active on macrophages, in the very early stages of the infection may allow C. trachomatis to escape some innate defences to establish infection. PMID- 11207589 TI - Constitutive PI3-K activity is essential for proliferation, but not survival, of Theileria parva-transformed B cells. AB - Theileria is an intracellular parasite that causes lymphoproliferative disorders in cattle, and infection of leucocytes induces a transformed phenotype similar to tumour cells, but the mechanisms by which the parasite induces this phenotype are not understood. Here, we show that infected B lymphocytes display constitutive phosphoinositide 3-kinase (PI3-K) activity, which appears to be necessary for proliferation, but not survival. Importantly, we demonstrate that one mechanism by which PI3-K mediates the proliferation of infected B lymphocytes is through the induction of a granulocyte-monocyte colony-stimulating factor (GM-CSF) dependent autocrine loop. PI3-K induction of GM-CSF appears to be at the transcriptional level and, consistently, we demonstrate that PI3-K is also involved in the constitutive induction of AP-1 and NF-kappaB, which characterizes Theileria-infected leucocytes. Taken together, our results highlight a novel strategy exploited by the intracellular parasite Theileria to induce continued proliferation of its host leucocyte. PMID- 11207590 TI - Cholera toxin and extracellular Ca2+ induce adherence of non-piliated Neisseria: evidence for an important role of G-proteins and Rho in the bacteria-cell interaction. AB - In this study, we characterize the interaction between non-piliated (P-) Neisseria gonorrhoeae and human epithelial cells. P- mutants lacking the pilus subunit protein PilE attach at low levels to cells. Although the binding may not lead to heavy inflammatory responses, the interaction between P- Neisseria and host cells most probably play a role in colonization and asymptomatic carriage of the pathogen. Here we show that the adherence of P N. gonorrhoeae is blocked by GDP-beta-S [guanosine 5'-O(thio)diphosphate], a non-hydrolyzable GTP analogue, and by C3 exotoxin, an inhibitor of the small G-protein Rho. G-protein activators such as cholera toxin, that activates Gs, and fluoroaluminate, a general G protein activator, induced bacterial adherence. Furthermore, increase of the extracellular free [Ca2+] dramatically enhanced adherence of non-piliated Neisseria. The pharynx and the urogenital tract are natural entry sites of the pathogenic Neisseria species, and at both sites the epithelial cells can be exposed to wide variations in Ca2+ concentration. Taken together, these data show the importance of extracellular Ca2+ in the pathogenic Neisseria-host interaction, and reveal a novel function of cholera toxin, namely induction of bacterial adherence. PMID- 11207591 TI - The microneme protein MIC3 of Toxoplasma gondii is a secretory adhesin that binds to both the surface of the host cells and the surface of the parasite. AB - Assay of the adhesion of cultured cells on Toxoplasma gondii tachyzoite protein Western blots identified a major adhesive protein, that migrated at 90 kDa in non reducing gels. This band comigrated with the previously described microneme protein MIC3. Cellular binding on Western blots was abolished by MIC3-specific monoclonal and polyclonal antibodies. The MIC3 protein affinity purified from tachyzoite lysates bound to the surface of putative host cells. In addition, T. gondii tachyzoites also bound to immobilized MIC3. Immunofluorescence analysis of T. gondii tachyzoite invasion showed that MIC3 was exocytosed and relocalized to the surface of the parasite during invasion. The cDNA encoding MIC3 and the corresponding gene have been cloned, allowing the determination of the complete coding sequence. The MIC3 sequence has been confirmed by affinity purification of the native protein and N-terminal sequencing. The deduced protein sequence contains five partially overlapping EGF-like domains and a chitin binding-like domain, which can be involved in protein-protein or protein-carbohydrate interactions. Taken together, these results suggest that MIC3 is a new microneme adhesin of T. gondii. PMID- 11207592 TI - Subversion of a young phagosome: the survival strategies of intracellular pathogens. PMID- 11207593 TI - Bacterial inhibition of phagocytosis. AB - The concerted study of molecular mechanisms of phagocytosis and the inhibition of phagocytosis by specific products of extracellular bacterial pathogens has borne considerable fruit. The importance of tyrosine phosphorylation and of the Rho family of GTPases has become clear to cell biologists, but pathogenic bacteria recognized the importance of these signalling pathways in phagocytic cells long ago. The discoveries described in this review are only the beginning. The simultaneous pursuit of the mechanisms and molecules involved in the initiation and regulation of phagocytosis and that pathogenic bacteria use to inhibit phagocytosis will surely identify more interesting pathways on each side of the contest. Are there any obvious possibilities? There are several bacterial factors that have the potential to inhibit known mechanisms of phagocytosis. Clostridium species, for example, make a number of exotoxins of interest. Clostridium botulinum and Clostridium tetani neurotoxins inactivate the regulated secretory machinery by proteolytic cleavage of SNARE proteins, and targets of tetanus toxin and botulinum b toxin inhibit the exocytotic delivery of membrane vesicles needed for phagocytosis of large particles (Hackam et al., 1998). Moreover, the C3 exotoxin of C. botulinum catalyses ADP ribosylation and inactivation of rho family GTPases (Wiegers et al., 1991), and toxins A and B of C. difficile UDP glucosylate and inactivate rho GTPases and thereby disrupt the actin cytoskeleton (Just et al., 1995a,b). However, as Clostridia lack the machinery for type III secretion, these proteins are not rapidly targeted to the phagocyte cytoplasm. More searching may reveal a pathogen that has combined the type III secretory machinery with clostridia toxin-like substrates. A potentially unique strategy for remaining outside phagocytes is exhibited by Helicobacter pylori, which contain a type IV secretion system. Unopsonized virulent strains of H. pylori bind readily to macrophages but are only internalized after a delay of several minutes. Such a delay appears to be sufficient for the bacteria to remain extracellular (Allen et al., 2000). Elucidation of the mechanism used by H. pylori to delay phagocytosis may reveal one or more novel virulence factors as well as one or more novel targets in the phagocyte that will add to the understanding of a fundamental process in host defence. Another field ripe for further mechanistic investigation is complement receptor-mediated phagocytosis. Dedicated study of the molecular events and molecular mediators of phagocytosis downstream of CR3 is likely to reveal interesting differences from FcgammaR phagocytosis and is just as likely to reveal that microbes have discovered unique mechanisms for circumventing them. Study of extracellular pathogens and the mechanisms that they use to remain outside phagocytic cells has revealed a great deal about the initial encounter between pathogen and phagocyte. We can look forward to additional discoveries about the host-pathogen interactions and the mechanisms and factors that each side uses to battle against the other. PMID- 11207594 TI - Type III secretion systems: what is the translocator and what is translocated? PMID- 11207595 TI - Actin induction during PMA and cAMP-dependent signal pathway activation in Entamoeba histolytica trophozoites. AB - Activation of PKC or cAMP-dependent signalling pathways in Entamoeba histolytica triggers the phosphorylation of proteins involved in actin rearrangements necessary for adhesion and locomotion. Analogous motifs to SRE and CRE sequences- known to respond to PMA and cAMP--were identified within the 5' regulatory region (5'RR) of one of the parasite actin genes. These sequences could be involved in the actin transcriptional upregulation reported during signalling. To test this hypothesis, a plasmid containing the 5'RR of the actin gene fused to the bacterial neomycin gene (neo) was used for stable transfection. Expression of neo and endogenous actin was measured after stimulation of transfected amoebae by PMA and dcAMP. It was found that both compounds induced neo and actin expression and showed a co-operative effect in the induction of neo. Induction by PMA or dcAMP failed if the directing amoebic 5'RR lacked SRE and CRE motifs. Transfection of amoebae with plasmid constructs, containing either progressive deletions of the actin 5'RR or site-directed mutations of the SRE and CRE-like motifs, corroborated that these sequences and a co-ordinated participation of PKC- and PKA-activated transcription factors are responsible for the increments in neo and actin mRNAs. In vivo, these PMA and cAMP-response elements could play an important role in regulating actin expression and organization in signalling processes activated during tissue invasion. PMID- 11207596 TI - The Yersinia tyrosine phosphatase YopH targets a novel adhesion-regulated signalling complex in macrophages. AB - The Yersinia protein tyrosine phosphatase (PTP) YopH is translocated into eukaryotic cells by a type III secretion system that requires bacterial-host cell contact. YopH is composed of two modular effector domains: a substrate-binding domain located in the N-terminal region (residues 1-130) and a PTP catalytic domain located in the C-terminal region (residues 206-468). Previous studies have shown that YopH selectively targets tyrosine-phosphorylated proteins of approximate molecular weight 120 kDa (p120) and 55 kDa (p55) in murine macrophages. It has been demonstrated that p120 actually represents two tyrosine phosphorylated target proteins, Cas and Fyb. We used the substrate-binding domain of YopH to affinity purify tyrosine-phosphorylated target proteins from lysates of J774A.1 macrophages. Protein microsequencing identified p55 as murine SKAP HOM. Direct interaction between SKAP-HOM and a catalytically inactive form of YopH was demonstrated in vitro and in macrophages. In addition, we obtained evidence that SKAP-HOM is tyrosine phosphorylated in response to macrophage cell adhesion and that it forms a signalling complex with Fyb. We suggest that dephosphorylation of SKAP-HOM and Fyb by YopH allows yersiniae to interfere with a novel adhesion-regulated signal transduction pathway in macrophages. PMID- 11207598 TI - Interaction of Bartonella henselae with endothelial cells results in rapid bacterial rRNA synthesis and replication. AB - Bartonella henselae is a slow-growing microorganism and the causative pathogen of bacillary angiomatosis in man. Here, we analysed how interaction of B. henselae with endothelial cells might affect bacterial growth. For this purpose, bacterial rRNA production and ribosome content was determined by fluorescence in situ hybridization (FISH) using rRNA-targeted fluorescence-labelled oligonucleotide probes. B. henselae grown on agar plates showed no detectable rRNA content by means of FISH, whereas B. henselae co-cultured with endothelial cells showed a rapid increase of rRNA production within the first 18 h after inoculation. The increased rRNA synthesis was paralleled by a approximately 1000-fold intracellular bacterial replication, whereas bacteria grown on agar base showed only a approximately 10-fold replication within the first 48 h of culture. Pretreatment of host cells with paraformaldehyde prevented adhesion, invasion, intracellular replication and bacterial rRNA synthesis of B. henselae. In contrast, inhibition of host cell protein synthesis by cycloheximide did not affect bacterial adhesion and invasion, but prevented intracellular replication although bacterial rRNA content was increased. Inhibition of actin polymerization by cytochalasin D did not affect adhesion, invasion, increased rRNA content or intracellular replication of B. henselae. These results demonstrate that rRNA synthesis and replication of B. henselae is promoted by viable host cells with intact de novo protein synthesis. PMID- 11207597 TI - Macrophage subsets harbouring Leishmania donovani in spleens of infected BALB/c mice: localization and characterization. AB - The purpose of the current study was to characterize parasite-containing cells located in spleens of BALB/c mice infected with Leishmania donovani. In particular, expression of MHC class II molecules by these cells was examined to determine whether they could potentially act as cells capable of immunostimulating Leishmania-reactive CD4+ T lymphocytes. To this end, an immunohistological analysis of spleens taken at various time points after infection was undertaken. Using this approach, we observed, in the red pulp, the formation of small cellular infliltrates containing heavily infected macrophages that could be stained with the monoclonal antibodies MOMA-2 and FA/11. All of them expressed high levels of MHC class II molecules. Parasites were also detected in the white pulp, especially in MOMA-2+, FA/11+ and MHC class II+ macrophages of the periarteriolar lymphocyte sheath and in MOMA-2+ marginal zone macrophages. Infected cells were further characterized by fluorescence microscopy after their enrichment by adherence. All infected mononuclear cells recovered by this procedure could be stained with MOMA-2 and FA/11 and thus very probably belonged to the mononuclear phagocyte lineage. Furthermore, all of them strongly expressed both MHC class II as well as H-2M molecules, regardless of the time points after infection. Analysis of the parasitophorous vacuoles (PV) by confocal microscopy showed that these compartments were surrounded by a membrane enriched in lysosomal glycoproteins lamp-1 and lamp-2, in macrosialin (a membrane protein of prelysosomes recognized by FA/11) and in MOMA-2 antigen. About 80% of the PV also had MHC class II and H-2M molecules on their membrane. Altogether, these data indicate that in the spleens of L. donovani-infected mice, a high percentage of amastigotes are located in macrophages expressing MHC class II molecules and that they live in PV exhibiting properties similar to those of PV detected in mouse bone marrow-derived macrophages exposed to a low dose of interferon gamma (IFN-gamma) and infected in vitro. PMID- 11207599 TI - The regulatory protein PhoP controls susceptibility to the host inflammatory response in Shigella flexneri. AB - The PhoP/PhoQ two-component regulatory system controls transcription of several key virulence genes essential for Salmonella survival in the host cell phagosome. Here, we determine that the PhoP/PhoQ system also regulates virulence in the aetiological agent of bacillary dysentery, Shigella flexneri, even though this pathogen escapes from the phagosome into the cytoplasm of the host cell. A phoP mutant of Shigella established infections and induced an acute inflammatory response in two different animal models. However, infections with phoP mutant bacteria were resolved more rapidly than infections with wild-type Shigella. Moreover, the Shigella phoP mutant was more sensitive than the wild-type strain to killing by polymorphonuclear leucocytes (PMNs), cationic polypeptides extracted from PMNs and other animal-derived antimicrobial peptides. The phoP mutant, however, invaded epithelial cells, spread intercellularly, induced apoptosis in macrophages and tolerated extreme acid pH as efficiently as the wild type strain. PhoP appears to regulate Shigella susceptibility to PMNs and antimicrobial molecules that are important for the late stages of infection with this enteric bacterium. PMID- 11207600 TI - Early Bacillus anthracis-macrophage interactions: intracellular survival survival and escape. AB - This study describes early intracellular events occurring during the establishment phase of Bacillus anthracis infections. Anthrax infections are initiated by dormant endospores gaining access to the mammalian host and becoming engulfed by regional macrophages (Mphi). During systemic anthrax, late stage events include vegetative growth in the blood to very high titres and the synthesis of the anthrax exotoxin complex, which causes disease symptoms and death. Experiments focus on the early events occurring during the first few hours of the B. anthracis infectious cycle, from endospore germination up to and including release of the vegetative cell from phagocytes. We found that newly vegetative bacilli escape from the phagocytic vesicles of cultured Mphi and replicate within the cytoplasm of these cells. Release from the Mphi occurs 4-6 h after endospore phagocytosis, timing that correlates with anthrax infection of test animals. Genetic analysis from this study indicates that the toxin plasmid pXO1 is required for release from the Mphi, whereas the capsule plasmid pXO2 is not. The transactivator atxA, located on pXO1, is also found to be essential for release, but the toxin genes themselves are not required. This suggests that Mphi release of anthrax bacilli is atxA regulated. The putative 'escape' genes may be located on the chromosome and/or on pXO1. PMID- 11207601 TI - The invasion protein InIB from Listeria monocytogenes activates PLC-gamma1 downstream from PI 3-kinase. AB - Entry of the bacterial pathogen Listeria monocytogenes into non-phagocytic mammalian cells is mainly mediated by the InlB protein. Here we show that in the human epithelial cell line HEp-2, the invasion protein InlB activates sequentially a p85beta-p110 class I(A) PI 3-kinase and the phospholipase C-gamma1 (PLC-gamma1) without detectable tyrosine phosphorylation of PLC-gamma1. Purified InlB stimulates association of PLC-gamma1 with one or more tyrosine phosphorylated proteins, followed by a transient increase in intracellular inositol 1,4,5-trisphosphate (IP3) levels and a release of intracellular Ca2+ in a PI 3-kinase-dependent manner. Infection of HEp-2 cells with wild-type L. monocytogenes bacteria also induces association of PLC-gamma1 with phosphotyrosyl proteins. This interaction is undetectable upon infection with a deltainlB mutant revealing an InlB specific signal. Interestingly, pharmacological or genetic inactivation of PLC-gamma1 does not significantly affect InlB-mediated bacterial uptake, suggesting that InlB-mediated PLC-gamma1 activation and calcium mobilization are involved in post-internalization steps. PMID- 11207602 TI - Surface-targeted lysosomal membrane glycoprotein-1 (Lamp-1) enhances lysosome exocytosis and cell invasion by Trypanosoma cruzi. AB - To gain entry into non-phagocytic cells, Trypanosoma cruzi trypomastigotes recruit lysosomes to the host cell surface. Lysosome fusion at the site of parasite entry leads to the formation of a parasitophorous vacuole with lysosomal properties. Here, we show that increased expression of the lysosomal membrane glycoprotein Lamp-1 at the cell surface renders CHO cells more susceptible to trypomastigote invasion in a microtubule-dependent fashion. Mutation of critical residues in the lysosome-targeting motif of Lamp-1 abolished the enhancement of T. cruzi invasion. This suggests that interactions dependent on Lamp-1 cytoplasmic tail motifs, and not the surface-exposed luminal domain, modulate T. cruzi entry. Measurements of Ca2+-triggered exocytosis of lysosomes in these cell lines revealed an enhancement of beta-hexosaminidase release in cells expressing wild-type Lamp-1 on the plasma membrane; this effect was not observed in cell lines transfected with Lamp-1 cytoplasmic tail mutants. These results also implicate Ca2+-regulated lysosome exocytosis in cell invasion by T. cruzi and indicate a role for the Lamp-1 cytosolic domain in promoting more efficient fusion of lysosomes with the plasma membrane. PMID- 11207603 TI - Listeriolysin O-induced stimulation of mucin exocytosis in polarized intestinal mucin-secreting cells: evidence for toxin recognition of membrane-associated lipids and subsequent toxin internalization through caveolae. AB - Lysteriolysin O (LLO) induces a microtubule-dependent activation of mucin exocytosis in the human mucin-secreting HT29-MTX. Cholesterol inhibits the LLO induced mucin exocytosis, whereas the oxidized form of cholesterol had no inhibitory effect. LLO-induced mucin exocytosis inhibited by cholesterol can be restored by enzymatic treatment with cholesterol oxidase. Inhibition of cholesterol synthesis in HT29-MTX cells results in a decrease in the LLO-induced mucin exocytosis. Other lipids such as gangliosides are able to inhibit the LLO induced mucin exocytosis, suggesting that the binding of the toxin occurs at a multiplicity of membrane-associated lipids acting as receptors. Incubation of the toxin with lipids such as cholesterol or gangliosides does not decrease binding of LLO to target membranes. The present work also provides evidence that the LLO induced mucin exocytosis develops independently of the pore-forming activity of the toxin. Finally, we demonstrated that the toxin associates with detergent insoluble glycolipid microdomains (DIGs) containing VIP/21 caveolin, allowing internalization of the toxin and subsequent activation of the mucin exocytosis. PMID- 11207604 TI - The anaerobic pathogen Clostridium perfringens can escape the phagosome of macrophages under aerobic conditions. AB - Clostridium perfringens is the most common cause of gas gangrene (clostridial myonecrosis), a disease that begins when ischaemic tissues become contaminated with C. perfringens vegetative cells or spores. An aerotolerant anaerobe, C. perfringens quickly multiplies in ischaemic tissues and spreads to healthy areas, leading to a high level of morbidity and mortality. As a species, the bacterium can synthesize 13 different toxins, and these are thought to be the major virulence factors of the disease. However, we present evidence here that C. perfringens can also persist inside macrophages, under aerobic conditions, by escaping the phagosome into the cytoplasm. C. perfringens was not killed by the cells of a clone (J774-33) of the macrophage-like murine cell line J774A.1 under aerobic or anaerobic conditions, whereas the non-pathogenic bacterium Bacillus subtilis was killed by J774-33 cells under both conditions. Electron microscopy images showed that C. perfringens cells were intact and resided mostly in the cytoplasm of J774-33 cells, whereas B. subtilis was in the phagosome. Immunofluorescence microscopy showed that intracellular C. perfringens bacteria failed to co-localize with the late endosome-lysosomal marker glycoprotein LAMP 1, whereas B. subtilis did co-localize with LAMP-1. C. perfringens also appeared to escape the phagosome of both activated and unactivated mouse peritoneal macrophages, but not as efficiently as was seen with the J774-33 cell line. In addition, cytochalasin D was used to show that phagocytosis of C. perfringens was dependent on actin polymerization and that the bacteria attach to J774-33 cells at distinct areas of the cell membrane. We propose that the ability to escape the phagosome and persist inside macrophages is an important factor in the early stages of a gangrene infection, when bacterial numbers are low and phagocytic cells are present. PMID- 11207605 TI - Co-operative binding of human fibronectin to Sfbl protein triggers streptococcal invasion into respiratory epithelial cells. AB - Streptococcal fibronectin binding protein I (SfbI) mediates adherence to and invasion of Streptococcus pyogenes into human epithelial cells. In this study, we analysed the binding activity of distinct domains of SfbI protein towards its ligand, the extracellular matrix component fibronectin, as well as the biological implication of the binding events during the infection process. By using purified recombinant SfbI derivatives as well as in vivo expressed SfbI domains on the surface of heterologous organism Streptococcus gordonii, we were able to dissociate the two major streptococcal target domains on the human fibronectin molecule. The SfbI repeat region exclusively bound to the 30 kDa N-terminal fragment of fibronectin, whereas the SfbI spacer region exclusively bound to the 45 kDa collagen-binding fragment of fibronectin. In the case of native surface expressed SfbI protein, an induced fit mode of bacteria-fibronectin interaction was identified. We demonstrate that binding of the 30 kDa fibronectin fragment to the repeat region of SfbI protein co-operatively activates the adjacent SfbI spacer domain to bind the 45 kDa fibronectin fragment. The biological consequence arising from this novel mode of fibronectin targeting was analysed in eukaryotic cell invasion assays. The repeat region of SfbI protein is mediating adherence and constitutes a prerequisite for subsequent invasion, whereas the SfbI spacer domain efficiently triggers the invasion process of streptococci into the eukaryotic cell. Thus, we were able to dissect bacterial adhesion from invasion by manipulating one protein. SfbI protein therefore represents a highly evolved prokaryotic molecule that exploits the host factor fibronectin not only for extracellular targeting but also for its subsequent activation that leads to efficient cellular invasion. PMID- 11207606 TI - Monitoring phase-specific gene expression in Histoplasma capsulatum with telomeric GFP fusion plasmids. AB - Dimorphism is an essential feature of Histoplasma capsulatum pathogenesis, and much attention has been focused on characteristics that are unique to the saprophytic mycelial phase or the parasitic yeast phase. Recently, we identified a secreted calcium-binding protein, CBP, that is produced in large amounts by yeast cells but is undetectable in mycelial cultures. In this study, the green fluorescent protein (GFP) was established as a reporter in H. capsulatum to study regulation of CBP1 expression in cultures and in single cells grown under different conditions and inside macrophages. One GFP version that was optimized for human codon usage yielded highly fluorescent Histoplasma yeast cells. By monitoring GFP fluorescence during the transition from mycelia to yeast, we demonstrated that the CBP1 promoter is only fully active after complete morphological conversion to the yeast form, indicating for the first time that CBP1 is developmentally regulated rather than simply temperature regulated. Continuous activity of the CBP1 promoter during infection of macrophages supports the hypothesis that CBP secretion plays an important role for Histoplasma survival within the phagolysosome. Broth cultures of Histoplasma yeasts carrying a CBP-GFP protein fusion construct were able to secrete a full-length fluorescent fusion protein that remained localized within the phagolysosomes of infected macrophages. Additionally, a comparison of two Histoplasma strains carrying the CBP1 promoter fusion construct either epichromosomally or integrated into the chromosome revealed cell-to-cell variation in plasmid copy number due to uneven plasmid partitioning into daughter cells. PMID- 11207607 TI - CAS/Crk signalling mediates uptake of Yersinia into human epithelial cells. AB - Uptake of Yersinia pseudotuberculosis into mammalian cells involves engagement of beta1 integrin receptors by the bacterial protein invasin. This triggers a host response that involves tyrosine phosphorylation of proteins and the induction of actin rearrangements that lead to cellular uptake of bacteria. In this report, we show that the focal adhesion protein CAS plays an important role in Yersinia uptake, and that its function is linked to the phosphorylation-dependent interaction between CAS and Crk. These studies demonstrate that Yersinia binding to host cell receptors initiates a cascade of events involving tyrosine phosphorylation of CAS, subsequent formation of functional CAS-Crk complexes and the activity of the small GTP-binding protein Rac1. The delineation of this pathway lends support for a model in which Yersinia uptake into human epithelial cells is dependent upon aspects of host signalling pathways that govern actin cytoskeleton remodelling and cell migration. PMID- 11207608 TI - Mycobacterium avium enters intestinal epithelial cells through the apical membrane, but not by the basolateral surface, activates small GTPase Rho and, once within epithelial cells, expresses an invasive phenotype. AB - Mycobacterium avium is a common pathogen in AIDS patients that is primarily (but not exclusively) acquired through the gastrointestinal tract, leading to the development of bacteraemia and disseminated disease. To cause infection through the gut, binding and invasion of the intestinal epithelial barrier are required. To characterize this process further, we determined the cell surface(s) (basolateral vs. apical membrane) that M. avium interacts with in intestinal mucosal cells in vitro. The level of binding and invasion of both HT-29 and Caco 2 intestinal cell monolayers by M. avium were similar when the assay was performed with control medium in the presence of Ca2+ (when only the apical surface was exposed), with Ca2+-depleted medium or with Ca2+-depleted medium + 1 mM EGTA (exposure of both apical and basolateral membranes), suggesting that the bacterium enters the apical surface of the epithelial lining. These observations were confirmed by assays in a transwell system and by using fluorescent microscopy. Real-time video microscopy showed that M. avium entry was not associated with membrane ruffling and the use of pharmacological inhibitors of the small GTPases demonstrated that M. avium invasion is dependent on the activation of the small GTPases Rho, but not on Rac or Cdc42. Passage of M. avium through HT-29 cells led to a phenotypic change (intracellular growth; IG) that was associated with a significantly greater (between five- and ninefold) ability to bind to and invade new monolayers of epithelial cells or macrophages when compared with the invasion by M. avium grown on agar (extracellular growth; EG). IG phenotype invasion of HT-29 cells also takes place only by the apical surface. M. avium enters intestinal epithelial cells by the apical surface and, once within the cells, changes phenotype, becoming more invasive towards both macrophages and other epithelial cells. PMID- 11207610 TI - Targeting of an enteropathogenic Escherichia coli (EPEC) effector protein to host mitochondria. AB - Many Gram-negative pathogens use a type III secretion apparatus to deliver effector molecules into host cells to subvert cellular processes in favour of the pathogen. Enteropathogenic Escherichia coli (EPEC) uses such a system to deliver the Tir effector molecule into host cells. In this paper, we show that the gene upstream of tir, orf19, encodes an additional type III secreted effector protein. Orf19 is delivered into host cells by a mechanism independent of endocytosis, but dependent on EspB. Orf19 is targeted to host mitochondria, where it appears to interfere with the ability to maintain membrane potential. Although the precise role of Orf19 remains to be elucidated, its interaction with mitochondria suggests a possible role in the subversion of key functions of these organelles, such as energy production or control of cell death. This is the first example of a type III secreted protein targeted to mitochondria; it is probable that homologues (present in EPEC and Shigella species) and other bacterial effectors will also target this organelle. PMID- 11207609 TI - Cytoplasmic tail motifs mediate endoplasmic reticulum localization and export of transmembrane reporters in the protozoan parasite Toxoplasma gondii. AB - In mammalian cells and yeasts, amino acid motifs in the cytoplasmic tails of transmembrane proteins play a prominent role in protein targeting in the early secretory pathway by mediating localization to or rapid export from the endoplasmic reticulum (ER). However, early sorting events are poorly characterized in protozoan parasites. Here, we show that a C-terminal QKTT sequence mediates the ER localization of chimeric reporter constructs consisting of bacterial alkaline phosphatase (BAP) fused to the transmembrane domain (TMD) and truncated cytoplasmic tail of the human low-density lipoprotein receptor (LDL) receptor or of murine lysosome-associated membrane protein (lamp-1) in Toxoplasma gondii. The cytoplasmic tail of human TGN46 also determines ER localization of BAP chimeras in the parasite, but this can be overcome by the addition at the C-terminus of the tail of an acidic patch, which functions as an ER export signal in conjunction with an upstream tyrosine motif. These results suggest that COPI-dependent ER retrieval and COPII-dependent export mechanisms mediated by KKXX and DXE motifs of mammalian cells are generally conserved in T. gondii. In contrast, the failure of the QKTT motif and TGN46 cytoplasmic tail to induce steady-state ER localization of vesicular stomatitis virus glycoprotein (VSVG) chimeras in HeLa and NRK cells indicates that significant differences in early secretory trafficking also exist. PMID- 11207611 TI - The relapsing fever spirochaete, Borrelia crocidurae, activates human endothelial cells and promotes the transendothelial migration of neutrophils. AB - The blood-borne, erythrocyte-aggregating Borrelia crocidurae, the causative agent of African relapsing fever, have been shown to induce severe cellular lesions in mice. In this paper, we present the first report of how the endothelium is stimulated during an African relapsing fever B. crocidurae infection. B. crocidurae co-incubated with cultured human umbilical vein endothelial cells (HUVECs) activated endothelium in such way that E-selectin and intercellular adhesion molecule 1 (ICAM-1) became upregulated in a dose- and time-dependent fashion, as determined by a whole-cell enzyme-linked immunosorbent assay (ELISA). The upregulation was reduced by treatment that killed the bacteria, suggesting that viability is important for the stimulation of HUVECs by B. crocidurae. Furthermore, conditioned medium from HUVECs stimulated with B. crocidurae contained interleukin (IL)-8, which is a chemotactic agent for neutrophils. Activation of HUVECs by B. crocidurae resulted in migration of subsequently added neutrophils across the endothelial monolayers, and this migration was inhibited by antibodies to IL-8. The activation of endothelium by B. crocidurae may constitute a key pathophysiological mechanism in B. crocidurae-induced vascular damage. PMID- 11207612 TI - Functional role for the class IX myosin myr5 in epithelial cell infection by Shigella flexneri. AB - Efficient control of Shigella-induced, rho-dependent cytoskeletal rearrangements seems to be required to shape the delicate cellular structures associated with bacterial invasion of epithelial cells. We therefore studied a class IX myosin and rho antagonist, the GTPase-activating protein (GAP) myr5, for a potential role in the bacterial entry process. We show that myr5 is recruited into bacterial entry spots. The recruitment pattern resembled that of rhoC or ezrin, but not rhoA, rac or CDC42, while in vitro GAP activity of myr5 was similar for rhoA, B or C. Analysis of myr5 mutants suggested that GTPase- or ATP-binding activites are not required for Shigella-induced recruitment of this atypical myosin to the bacterial entry site. Functional studies revealed a potential dual role of the myosin functions and the GAP module of myr5 for bacterial internalization. PMID- 11207613 TI - Caspase 3-dependent killing of host cells by the parasite Entamoeba histolytica. AB - The parasite Entamoeba histolytica is named for its ability to lyse host tissues. To determine the factors responsible, we have initiated an examination of the contribution of parasite virulence factors and host caspases to cellular destruction by the parasite. Amoebic colitis in C3H/HeJ mice was associated with extensive host apoptosis at sites of E. histolytica invasion. In vitro studies of E. histolytica-Jurkat T-cell interactions demonstrated that apoptosis required contact via the amoebic Gal/GalNAc lectin, but was unaffected by 75% inhibition of the amoebic cysteine proteinases. Parasite-induced DNA fragmentation was unaffected in caspase 8-deficient Jurkat cells treated with the caspase 9 inhibitor Ac-LEHD-fmk. In contrast, caspase 3-like activity was observed within minutes of E. histolytica contact and the caspase 3 inhibitor Ac-DEVD-CHO blocked Jurkat T cell death, as measured by both DNA fragmentation and 51Cr release. These data demonstrate rapid parasite-induced activation of caspase 3-like caspases, independent of the upstream caspases 8 and 9, which is required for host cell death. PMID- 11207614 TI - Host cell-derived sphingolipids are required for the intracellular growth of Chlamydia trachomatis. AB - Chlamydia trachomatis, an important cause of human disease, is an obligate intracellular bacterial pathogen that relies on the eukaryotic host cell for its replication. Recent reports have revealed that the C. trachomatis vacuole receives host-derived sphingolipids by fusing with trans-Golgi network (TGN)derived secretory vesicles. Here, it is shown that these lipids are required for the growth of the bacteria. C. trachomatis was unable to replicate at 39 degrees C in the Chinese hamster ovary (CHO)-derived cell line SPB-1, a cell line incapable of synthesizing sphingolipids at this temperature because of a temperature-sensitive mutation in the serine palmitoyltransferase (SPT) gene. Complementation with the wild-type SPT gene or addition of exogenous cell permeable sphingolipid precursors to the mutant cells restored their ability to support chlamydial replication. L-cycloserine (L-CS) and fumonisin B1 (FB1), inhibitors of sphingolipid biosynthesis, decreased the proliferation of the bacteria in eukaryotic cells at concentrations that also decreased host cell sphingolipid synthesis. In the case of FB1, the vacuoles appeared aberrant; the addition of sphingolipid precursors was able to reverse the altered morphology of the FB1-treated vacuoles. Collectively, these data strongly suggest that the growth and replication of chlamydiae is dependent on synthesis of sphingolipids by the eukaryotic host cell and may contribute to this organism's obligate intracellular parasitism. PMID- 11207615 TI - The gastrointestinal ecosystem: a precarious alliance among epithelium, immunity and microbiota. AB - The gastrointestinal (GI) tract is a complex ecosystem generated by the alliance of GI epithelium, immune cells and resident microbiota. The three components of the GI ecosystem have co-evolved such that each relies on the presence of the other two components to achieve its normal function and activity. Experimental systems such as cell culture, germ-free animal models and intestinal isografts have demonstrated that each member of the GI ecosystem can follow a predetermined developmental pathway, even if isolated from the other components of the ecosystem. However, the presence of all three components is required for full physiological function. Genetic or functional alterations of any one component of this ecosystem can result in a broken alliance and subsequent GI pathology. A more detailed understanding of the interactions among microbiota, GI epithelium and the immune system should provide insight into multiple human disease states. PMID- 11207616 TI - Overexpression of cysteine proteinase 2 in Entamoeba histolytica or Entamoeba dispar increases amoeba-induced monolayer destruction in vitro but does not augment amoebic liver abscess formation in gerbils. AB - To study the role of cysteine proteinases in the pathogenicity of Entamoeba histolytica, we have attempted to overexpress the three main cysteine proteinases (EhCP1, EhCP2, EhCP5) of this parasite in trophozoites of E. histolytica as well as in non-pathogenic Entamoeba dispar by episomal transfection. Although each of the corresponding coding sequences were cloned in identical expression plasmids, we were unable to overexpress EhCP1 and EhCP5, respectively, but could substantially induce expression of EhCP2 in both amoeba species by sevenfold, leading to a threefold increase in total cysteine proteinase activity. Overexpression of EhCP2 did not influence expression of other cysteine proteinases and could be attributed to an increase of a single 35 kDa activity band in substrate gel electrophoresis. In contrast to previous findings, which indicated that amoeba cysteine proteinases are involved in erythrophagocytosis and liver abscess formation, cells overexpressing EhCP2 showed no difference in erythrophagocytosis or liver abscess formation compared with respective controls. However, overexpression of EhCP2 in both amoeba species resulted in a marked increase of in vitro monolayer destruction. PMID- 11207617 TI - Interaction of Helicobacter pylori with professional phagocytes: role of the cag pathogenicity island and translocation, phosphorylation and processing of CagA. AB - Chronic infection of the human gastric mucosa with Helicobacter pylori is a major cause of gastroduodenal pathologies, including peptic ulcerations, mucosa associated lymphoid tissue (MALT) lymphoma and adenocarcinoma. Helicobacter pylori strains carrying the cag pathogenicity island, which encodes an active type IV protein secretion system (cag+ or type I strains), are preferentially associated with strong gastric inflammation and severe disease. We show here that cag+ H. pylori strains use the type IV secretion system to inject the bacterial protein CagA into various types of professional phagocytes, including human polymorphonuclear leucocytes (PMNs) and the human and murine macrophage cell lines THP-1 and J774A.1 CagA is rapidly tyrosine phosphorylated and proteolytically processed to generate a stable 35-45 kDa C-terminally tyrosine phosphorylated protein fragment. H. pylori was efficiently ingested by the different types of phagocytic cells. A chromosomal deletion of the complete pathogenicity island had no significant effect on the rate of ingestion. Furthermore, the survival rate of H. pylori in the phagosome was unchanged between the wild type and a deletion mutant lacking the type IV secretion system. Thus, the type IV secretion system seems to be involved neither in active phagocytosis resistance nor in prolonged survival of the bacteria in phagocytic cells. PMID- 11207618 TI - Expression of pathogen-like Opa adhesins in commensal Neisseria: genetic and functional analysis. AB - Several species of commensal Neisseriae (Cn) may colonize the human nasopharynx, but little is known about their adhesion mechanisms. We have investigated structural and functional similarities between adhesins of Cn and of Neisseria meningitidis (Nm), also a frequent colonizer of the nasopharynx. In this study, we demonstrate the expression of Opa-like proteins in nine strains of Cn. Phylogenetic analysis segregated the majority of the Cn Opa in a cluster separated from the pathogenic cluster with a few exceptions. One Opa, which located within the pathogenic cluster, was strikingly similar (74%) to an Opa of a Neisseria gonorrhoeae (Ng) strain and, like Ng, it lacked the extra Y11 or the 136DKF138 triplet insert, which are conserved among many N. meningitidis Opa proteins. Most importantly, the majority of the Cn Opa proteins were able to interact with human CEACAM1 (CD66a) molecules, previously identified as receptors for pathogenic Opa proteins. By the use of CEACAM1 N-domain mutants, we demonstrate that Cn Opa target the same region of the N-domain of the receptor as that used by Nm. Furthermore, Cn strains bound to cell-expressed human CEACAM1. In competition assays, adherent Cn strain C450, exhibiting high affinity for CEACAM1, was not displaced by a Nm isolate and vice versa. But in simultaneous incubation, Nm out-competed the Cn strain. This is the first study to demonstrate the expression of adhesins in Cn that are structurally and functionally closely related to pathogenic adhesins. The studies imply that some Cn have the potential to occupy and thus compete with the pathogens for receptors on human mucosa, their common and exclusive niche. PMID- 11207619 TI - Expression, activity and cytotoxicity of pertussis toxin S1 subunit in transfected mammalian cells. AB - Pertussis toxin (PT) comprises an active subunit (S1), which ADP-ribosylates the alpha subunit of several mammalian G proteins, and the B oligomer (S2-S5), which binds glycoconjugate receptors on cells. In a previous report, expression of S1 in Cos cells resulted in no observable cytotoxicity, and it was hypothesized that either S1 failed to locate its target proteins or the B oligomer was also necessary for cytotoxicity. To address this, we stably transfected S1 with and without a signal peptide into mammalian cells. Immunofluorescence analysis confirmed the function of the signal peptide. Surprisingly, we found that S1 was active in both transfectants, as determined by clustering of transfected Chinese hamster ovary (CHO) cells and ADP-ribosylation of G proteins. Constructs with a cysteine-to-serine change at residue 201 or a truncated S1 (residues 1-181) were also active when transfected into cells. Constructs with an inactive mutant S1 had no activity, confirming that the observed results were due to the activity of the toxin subunit. We conclude that S1 is active when expressed in mammalian cells without the B oligomer, that secretion into the endoplasmic reticulum does not prevent this activity and that the C-terminal portion of S1 is not required for its activity in cells. PMID- 11207620 TI - Genome ploidy in different stages of the Giardia lamblia life cycle. AB - The early diverging eukaryotic parasite Giardia lamblia is unusual in that it contains two apparently identical nuclei in the vegetative trophozoite stage. We have determined the nuclear and cellular genome ploidy of G. lamblia cells during all stages of the life cycle. During vegetative growth, the nuclei cycle between a diploid (2N) and tetraploid (4N) genome content and the cell, consequently, cycles between 4N and 8N. Stationary phase trophozoites arrest in the G2 phase with a ploidy of 8N (two nuclei, each with a 4N ploidy). On its way to cyst formation, a G1 trophozoite goes through two successive rounds of chromosome replication without an intervening cell division event. Fully differentiated cysts contain four nuclei, each with a ploidy of 4N, resulting in a cyst ploidy of 16N. The newly excysted cell, for which we suggest the term 'excyzoite', contains four nuclei (cellular ploidy 16N). In a reversal of the events occurring during encystation, the excyzoite divides twice to form four trophozoites containing two diploid nuclei each. The formation of multiple cells from a single cyst is likely to be one of the main reasons for the low infectious doses of G. lamblia. PMID- 11207621 TI - Gliding motility and cell invasion by Apicomplexa: insights from the Plasmodium sporozoite. AB - Apicomplexa constitute one of the largest phyla of protozoa. Most Apicomplexa, including those pathogenic to humans, are obligate intracellular parasites. Their extracellular forms, which are highly polarized and elongated cells, share two unique abilities: they glide on solid substrates without changing their shape and reach an intracellular compartment without active participation from the host cell. There is now ample ultrastructural evidence that these processes result from the backward movement of extracellular interactions along the anteroposterior axis of the parasite. Recent work in several Apicomplexa, including genetic studies in the Plasmodium sporozoite, has provided molecular support for this 'capping' model. It appears that the same machinery drives both gliding motility and host cell invasion. The cytoplasmic motor, a transmembrane bridge and surface ligands essential for cell invasion are conserved among the main apicomplexan pathogens. PMID- 11207622 TI - SifA permits survival and replication of Salmonella typhimurium in murine macrophages. AB - SifA was originally identified as a virulence factor required for formation of Salmonella-induced filaments (Sifs), elongated tubules rich in lysosomal glycoproteins that extend from the Salmonella-containing vacuole in infected epithelial cells. Here, we demonstrate that deletion mutants of ssaR, a component of the SPI-2 type III secretion system, do not form Sifs in HeLa epithelial cells. This suggests that SifA is a translocated effector of this system, acting within host cells to form Sifs. In support of this hypothesis, transfection of HeLa cells with a vector encoding SifA fused to the green fluorescent protein caused extensive vacuolation of LAMP-1-positive compartments. Filamentous tubules that closely resembled Sifs were also observed in transfected cells, demonstrating that SifA is sufficient to initiate alteration of host cell endosomal structures. deltasifA mutants were impaired in their ability to survive/replicate in RAW 264.7 murine macrophages, a phenotype similar to ssaR mutants. Our findings suggest that SifA is an effector of the SPI-2 type III secretion system and allows colonization of murine macrophages, the host niche exploited during systemic phases of disease in these animals. A family of SifA related proteins and their importance to Salmonella pathogenesis is also discussed. PMID- 11207623 TI - Rho GTPase activity modulates Pseudomonas aeruginosa internalization by epithelial cells. AB - The Gram-negative pathogen Pseudomonas aeruginosa invades epithelial cells in vivo and in vitro. We have examined the pathway(s) by which epithelial cells internalize P. aeruginosa strain PA103 using Madin-Darby canine kidney (MDCK) cells. We have recently demonstrated that P. aeruginosa internalization occurs by an actin-dependent Toxin B-inhibited pathway which becomes downregulated as epithelial cells become polarized, suggesting that one or more of the Rho family GTPases is involved in bacterial internalization. Here, we demonstrate that activation of the Rho family GTPases by cytotoxic necrotizing factor 1 (CNF-1) stimulates P. aeruginosa internalization. Examination of the roles of the individual Rho family GTPases in internalization shows that expression of a constitutively active allele of RhoA (RhoAV14), but not of constitutively active Rac1 (Rac1V12) or Cdc42 (Cdc42V12), is sufficient to increase uptake of PA103pscJ. This relative increase persists when bacterial infection is established at the basolateral surface of polarized cells, suggesting that the effect of RhoAV14 is not simply due to its known ability to disrupt tight junction integrity in polarized cells. RhoAV14-mediated stimulation of bacterial uptake is actin dependent as it is abrogated by exposure to latrunculin A. We also find that endogenous Rho GTP levels in epithelial cells are increased by infection with an internalized strain of P. aeruginosa; conversely, a poorly internalized isogenic strain expressing the bacterial anti-internalization protein ExoT causes decreased Rho GTP levels. Experimental inhibition of Rho, either by expressing dominant negative RhoAN19 or by inhibiting native Rho using a membrane permeable fusion construct of a Rho-specific inhibitor, C3 ADP ribosyltransferase, does not inhibit PA103pscJ internalization in MDCK or HeLa cells. Models consistent with these data are presented. PMID- 11207624 TI - Evidence that Dot-dependent and -independent factors isolate the Legionella pneumophila phagosome from the endocytic network in mouse macrophages. AB - Legionella pneumophila survives within macrophages by evading phagosome-lysosome fusion. To determine whether L. pneumophila resides in an intermediate endosomal compartment or is isolated from the endosomal pathway and to investigate what bacterial factors contribute to establishment of its vacuole, we applied a series of fluorescence microscopy assays. The majority of vacuoles, aged 2.5 min to 4 h containing post-exponential phase (PE) L. pneumophila, appeared to be separate from the endosomal pathway, as judged by the absence of transferrin receptor, LAMP-1, cathepsin D and each of four fluorescent probes used to label the endocytic pathway either before or after infection. In contrast, more than 70% of phagosomes that contained Escherichia coli, polystyrene beads, or exponential phase (E) L. pneumophila matured to phagolysosomes, as judged by co-localization with LAMP-1, cathepsin D and fluorescent endosomal probes. Surprisingly, neither bacterial viability nor the putative Dot/Icm transport complex was absolutely required for vacuole isolation; although phagosomes containing either formalin killed PE wild-type or live PE dotA or dotB mutant L. pneumophila rapidly accumulated LAMP-1, less than 20% acquired lysosomal cathepsin D or fluorescent endosomal probes. Therefore, a Dot-dependent factor(s) isolates the L. pneumophila phagosome from a LAMP-1-containing compartment, and a formalin resistant Dot-independent activity inhibits vacuolar accumulation of endocytosed material and delivery to the degradative lysosomes. PMID- 11207625 TI - Helicobacter pylori-mediated transcriptional regulation of the human beta defensin 2 gene requires NF-kappaB. AB - Human beta-defensin 2 (hBD-2) is an antimicrobial peptide involved in host defence against bacterial infection in epithelial tissues. Its levels are dramatically increased after bacterial infection. The involvement of NF-kappaB in Helicobacter pylori-mediated induction of hBD-2 promoter activity was examined. A luciferase reporter plasmid containing the hBD-2 promoter extending from -2110 base pairs to -1 was transiently expressed in MKN45 cells, and promoter activity was determined after incubation with H. pylori for 6 h. Deletion or mutation of the NF-kappaB site at -208 abolished activation of the hBD-2 promoter. Only H. pylori strains carrying a cag pathogenicity island (PAI) induced activation of the NF-kappaB site of the hBD-2 promoter gene. By gel retardation analyses, H. pylori increased NF-kappaB binding to hBD-2 promoter gene sequences. Supershift analysis demonstrated that whereas H. pylori activated NF-kappaB p65-p65 and p50 p50 homodimers, and the p65-p50 heterodimer of NF-kappaB, only the p65-p65 homodimer bound to the NF-kappaB site of the hBD-2 promoter. Thus, specific NF kappaB proteins are important cis-elements for induction of hBD-2 gene transcription by H. pylori. PMID- 11207626 TI - Growth hormone and the heart. AB - Impaired cardiovascular function has recently been demonstrated to potentially reduce life expectancy both in GH deficiency and excess. Experimental and clinical studies have supported the evidence that GH and IGF-I are implicated in cardiac development. In most patients with acromegaly a specific cardiomyopathy, characterized by myocardial hypertrophy with interstitial fibrosis, lympho mononuclear infiltration and areas of monocyte necrosis, results in biventricular concentric hypertrophy. In contrast, patients with childhood or adulthood-onset GH deficiency (GHD) may suffer both from structural cardiac abnormalities, such as narrowing of cardiac walls, and functional impairment, that combine to reduce diastolic filling and impair left ventricular response to peak exercise. In addition, GHD patients may have an increase in vascular intima-media thickness and a higher occurrence of atheromatous plaques, that can further aggravate the haemodynamic conditions and contribute to increased cardiovascular and cerebrovascular risk. However, several lines of evidence have suggested that the cardiovascular abnormalities can be partially reversed by suppressing GH and IGF I levels in acromegaly or after GH replacement therapy in GHD patients. Recently, much attention has been focussed on the ability of GH to increase cardiac mass suggesting its possible use in the treatment of chronic nonendocrine heart failure. In fact, GH administration can induce an improvement in haemodynamic and clinical status in some patients. Although these data need to be confirmed in more extensive studies, such promising results seem to open new perspectives for GH treatment in humans. PMID- 11207627 TI - Hypertension, aortic dilatation and aortic dissection in Turner syndrome: a potentially lethal triad. PMID- 11207628 TI - Oestrogen replacement in young women with Turner's syndrome. PMID- 11207629 TI - Choosing an oestrogen replacement therapy in young adult women with Turner syndrome. AB - OBJECTIVE: Hormone replacement therapy (HRT) is prescribed to most patients with Turner syndrome (TS) although its use in adult TS patients has not been scientifically evaluated. The present study was performed to compare the short term effects in adult women with Turner syndrome of low-dose oral conjugated oestrogen (0.625 mg, CE) with relatively high dose ethinyl oestradiol (30 microg, EE2); both combined with an oral progestin. DESIGN AND PATIENTS: After 4 months off HRT, 17 young, otherwise healthy women with TS were enrolled in a random, unblinded, crossover study of the two oestrogenic preparations, each given for 6 months. MEASUREMENTS: We compared parameters of oestrogenic activity that would cover immediate changes in hormone levels, biochemistry, bone turnover, uterine and cardiac variables, which constitute risk factors for later development of diabetes, atherosclerosis, osteoporosis and aortic dissection. RESULTS: Serum FSH returned to normal follicular phase levels only on the EE2 regimen. The hypotrophic endometria normalized with either of the two oestrogen regimens with no excessive hypertrophy. Hyperinsulinaemia was suppressed to normal by both EE2 and CE. PTH and 1,25-dihydroxyvitamin D levels increased on HRT (EE2 > CE), and phosphorus decreased. Alkaline phosphatase, osteocalcin and urinary deoxypyridinoline cross-links (DPD) were high off therapy; the former two suppressed to high-normal levels on the EE2 regimen, but not on CE, and DPD did not normalize with either HRT. Lipid profiles in these young TS patients were normal. Liver enzymes were mildly elevated off therapy and suppressed to normal levels on both regimens, but more so with EE2. CONCLUSIONS: The risk factors embodied in hyperinsulinaemia and enhanced bone turnover which, ultimately, have consequences for TS morbidity, are minimized by HRT. In the short term, neither regimen is effective for bone turnover in adult women with Turner syndrome. PMID- 11207630 TI - Effects of peroral and transdermal oestrogen replacement therapy on glucose and insulin metabolism. AB - OBJECTIVE: Conflicting data have been reported previously on the effects of oestrogen replacement therapy on glucose tolerance, and the effects on glycosylated haemoglobin GHbA(1c) have been studied only among diabetics. The objective of this study was to evaluate the effects on glucose and insulin metabolism among nondiabetic women and to compare the outcomes of peroral and transdermal modes of administration. DESIGN: The effects of peroral oestradiol valerate 2 mg/day with placebo gel were compared to those of transdermal 17 beta oestradiol gel (1 mg oestradiol/day) and placebo tablets in a randomised, double blind, double-dummy study for six months. PATIENTS: Seventy-nine hysterectomised, nondiabetic postmenopausal women, 39 women in the peroral oestrogen group and 40 in the gel group. MEASUREMENTS: Oral glucose tolerance tests (OGTT) with blood glucose, serum C-peptide and insulin determinations were performed. GHbA(1c), IGF I and IGFBP-1 were measured at baseline and after six months of therapy. In addition, insulin sensitivity and insulin secretion indices were obtained from OGTT. RESULTS: A small significant reduction in the GHbA(1c) concentration was observed during both peroral (P < 0.05) and transdermal oestrogen therapy (P < 0.05). However, no effect on insulin sensitivity was observed. The response to a standard 75 g oral glucose load was similar in the study groups. Compared with the baseline values, the area under the curve for C-peptide decreased by 8% both in the peroral group (P < 0.05) and in the gel group (P < 0.01). The fasting and postchallenge glucose and insulin levels or insulin release indices were not significantly altered. Peroral oestrogen decreased IGF-I and increased IGFBP-1, but these findings were not associated with the changes in glucose metabolism. CONCLUSIONS: Neither peroral nor transdermal oestradiol replacement therapy seemed to induce any negative effects on glucose metabolism over a time period of 6 months. PMID- 11207631 TI - Oestradiol improves arterial endothelial function in healthy men receiving testosterone. AB - OBJECTIVE: To assess prospectively the effects of low dose oestradiol on arterial endothelial and smooth muscle function in healthy men. Oestrogen use is associated with reduced cardiovascular disease in oestrogen-deficient women, however, the vascular effects of low-dose oestradiol in healthy men have not been investigated previously. PATIENTS AND DESIGN: Twenty-three men (aged 32 +/- 8 years) were randomized to receive depot implants of testosterone (T) alone (group 1, n = 10), or T with either 10 mg (group 2, n = 7) or 20 mg (group 3, n = 6) of oestradiol (E). MEASUREMENTS: Hormone levels, lipids and vascular reactivity were measured before, 1 month and 6 months after hormone implantation. Using high resolution ultrasound, brachial artery diameter was measured at rest, during reactive hyperaemia (leading to flow-mediated dilatation, FMD, which is endothelium-dependent) and after sublingual nitroglycerin (GTN, an endothelium independent dilator). RESULTS: Oestradiol produced a dose-dependent increase in plasma oestradiol (at 1 month 96 +/- 7, 149 +/- 6, 192 +/- 23 pmol/l in the 3 groups, respectively, P < 0.001 by ANOVA for trend). Minor side-effects (gynaecomastia, nipple tenderness) indicated that 20 mg oestradiol was the maximum tolerated dose. There was also a dose-dependent increase in FMD with oestradiol dose: at 1 month, - 0.2, + 0.2 and + 1.8% for groups 1-3, respectively (P = 0.31 by ANOVA for trend); and at 6 months, - 0.8, + 0.4 and + 2.2% (P = 0.02). The rise in oestradiol levels following treatment correlated with the improvement in FMD (P = 0.01). GTN responses were similar in the 3 groups throughout the study. CONCLUSION: In healthy young men, oestradiol supplementation is associated with enhanced arterial endothelial function, a key marker of vascular health. PMID- 11207632 TI - Hypogonadism in patients with acromegaly: data from the multi-centre acromegaly registry pilot study. AB - OBJECTIVE: Because acromegaly is an uncommon disorder, epidemiological data regarding the demographics of the disease such as the prevalence of hypogonadism have been limited. In order to derive clinical and epidemiological information, including underlying hormonal factors, regarding hypogonadism in patients with acromegaly, we performed a pilot study designed to develop a multi-centre acromegaly patient registry. DESIGN AND MEASUREMENTS: Medical records of patients with acromegaly seen between 1976 and 1996 at three Institutions were reviewed, and data were entered into a database using a secure internet website. Hypogonadism was defined as amenorrhoea in women and testosterone deficiency in men. Subanalysis was performed in patients with microadenomas and women less than 50 years of age, to include women of reproductive age. RESULTS: Information was available on 363 patients, of whom 54% were women. The mean age at diagnosis was 41 +/- 13 years. In subjects less than 50 years of age, hypogonadism was present in 59%. Hyperprolactinaemia was present in 45% and 21% of hypogonadal and eugonadal patients of reproductive age, respectively (P = 0.0003). GH levels were higher in patients with hypogonadism (P = 0.03). In patients < 50 years of age with microadenomas, hypogonadism was present in nine of the 22 (41%) patients, including 55% of the women and 27% of the men (P = ns). Hyperprolactinaemia was present in three of the 10 and four of the 14 of microadenoma patients with hypogonadism and eugonadism, respectively. CONCLUSION: We developed a web-based acromegaly patient registry and used it to show that hypogonadism is a frequent consequence of acromegaly, even in patients with microadenomas, who are not at risk from hypopituitarism due to local mass effects. We also demonstrated that prolactin and GH hypersecretion contribute to the pathogenesis of hypogonadism in acromegaly, and that hypogonadism may occur in microadenoma patients even in the absence of hyperprolactinaemia. PMID- 11207633 TI - Relationship between blood pressure and glucose tolerance in acromegaly. AB - BACKGROUND: Hypertension represents a well-known risk factor for cardiovascular diseases. The pathogenesis of hypertension in acromegaly is commonly viewed as multifactorial, but the possible influence of metabolic disorders on blood pressure (BP) in affected patients is largely unknown. OBJECTIVE: The aim of the present study was to evaluate the impact of glucose metabolism abnormalities on BP values in a series of patients with active acromegaly. DESIGN: An open multicentre prospective study. PATIENTS: Sixty-eight patients with active disease, aged 47.5 +/- 11.7 years, have been studied. Thirty-nine had normal glucose tolerance (NGT), 16 impaired glucose tolerance (IGT) and 13 suffered from diabetes mellitus (DM). MEASUREMENTS: Mean clinical BP values were calculated as the mean of BP values obtained by sphygmomanometric measurement in three separate occasions and mean 24-h, diurnal and nocturnal systolic (SBP) and diastolic (DBP) values were obtained by 24-h ambulatory blood pressure monitoring (ABPM). RESULTS: Patient's age and the degree of glucose tolerance abnormalities were found to significantly and independently influence BP values. All clinical and ABPM SBP and DBP values significantly increased with age by linear regression (P < 0.02 for all BP values, 0.30 < or = R < or = 0.43), and the independent influence of this parameter on BP values was confirmed by mutivariate analysis. Similarly, the independent influence of glucose tolerance abnormalities on BP values was confirmed when introducing age as a covariable in a multivariate analysis, and patients with DM presented significantly higher clinical SBP and 24 h, diurnal and nocturnal SBP and DBP than patients with NGT (P < 0.02 for clinical SBP, P < 0.015 for all ABPM values, respectively). In addition, patients with DM showed significantly higher 24-h, diurnal and nocturnal DBP than those with IGT (P < 0.05 in all cases). In contrast, no significant difference was found between NGT and IGT patients. No significant influence of disease duration, BMI, GH, IGF-I, or fasting and 2-h post glucose load insulinaemia on BP values was observed. CONCLUSIONS: Abnormalities of glucose metabolism significantly contribute to increase systolic blood pressure and especially diastolic blood pressure in acromegalic patients. Careful control of blood pressure and of risk factors for developing systemic hypertension, with special reference to glucose tolerance, is mandatory to decrease cardiovascular morbidity and mortality in such patients. PMID- 11207634 TI - Determinants of changes in plasma homocysteine in hyperthyroidism and hypothyroidism. AB - OBJECTIVE: Hyperhomocysteinaemia is a risk factor for premature atherosclerotic vascular disease and venous thrombosis. The aim of the present study was to assess plasma total homocysteine (tHCys) concentrations in hypo- as well as hyperthyroid patients before and after treatment, and to evaluate the role of potential determinants of plasma tHCys levels in these patients. DESIGN: Prospective follow up study. PATIENTS: Fifty hypothyroid and 46 hyperthyroid patients were studied in the untreated state and again after restoration of euthyroidism. MEASUREMENTS: Fasting plasma levels of tHCys and its putative determinants (plasma levels of free thyroxine (fT4), folate, vitamin B(12), renal function, sex, age, smoking status and the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene were measured before and after treatment. RESULTS: Restoration of the euthyroid state decreased both tHCys (17.6 +/- 10.2-13.0 +/- 4.7 micromol/l; P < 0.005) and creatinine (83.9 +/- 22.0-69.8 +/- 14.2 micromol/l; P < 0.005) in hypothyroid patients and increased both tHCys (10.7 +/- 2.5-13.4 +/- 3.3 micromol/l; P < 0.005) and creatinine (49.0 +/- 15.4 66.5 +/- 15.0 micromol/l; P < 0.005) in hyperthyroid patients (values as mean +/- SD). Folate levels were lower in the hypothyroid group compared to the hyperthyroid group (11.7 +/- 6.4 and 15.1 +/- 7.6 nmol/l; P < 0.05). Pretreatment tHCys levels correlated with log fT(4) (r = - 0.47), folate (r = - 0.21), plasma creatinine (r = 0.45) and age (r = 0.35) but not with C677T genotype. Multivariate analysis indicated that pretreatment log(fT(4)) levels and age accounted for 28% the variability of pre-treatment tHCys (tHCys = 14.2-5.50 log(fT(4)) + 0.14 age). After treatment the logarithm of the change (Delta) in fT(4) (expressed as the post-treatment fT(4)/pre-treatment fT(4) ratio) accounted for 45% of the variability in change of tHCys ( tHCys = - 0.07-4.94 log ( fT(4))); there was no independent contribution of changes in creatinine which was, however, strongly related to changes in tHCys (r = 0.61). CONCLUSIONS: Plasma tHCys concentrations increased in hypothyroidism and decreased in hyperthyroidism. Plasma fT(4) is an independent determinant of tHCys concentrations. Lower folate levels and a lower creatinine clearance in hypo thyroidism, and a higher creatinine clearance in hyperthyroidism only partially explain the changes in tHCys. PMID- 11207635 TI - The usefulness of quantitative orbital magnetic resonance imaging in Graves' ophthalmopathy. AB - BACKGROUND: Two-thirds of patients with Graves' ophthalmopathy (GO) respond to immunosuppressive treatment (prednisone or orbital irradiation), but one-third do not respond. Responders are likely to be in the active, oedematous stage of the eye disease, nonresponders in the inactive fibrotic stage. Clinical distinction between the two stages can be difficult. Quantitative magnetic resonance imaging (MRI) might be helpful in this respect, as T2 relaxation times are longer in oedematous than in fibrotic tissues. STUDY DESIGN: Prospective study on quantitative orbital MRI in healthy subjects and patients with moderately severe GO, evaluating T2 relaxation time of extraocular muscles (EOM): (a) in patients vs. controls, and (b) in patients, as a predictor of outcome to orbital irradiation. SUBJECTS AND MEASUREMENTS: Nine healthy volunteers and 64 consecutive patients with moderately severe untreated GO, who were euthyroid for > or = 2 months and qualified for orbital irradiation. T2 relaxation times were measured at the site of the largest diameter in all eight EOM of each subject. Baseline T2 values in patients were related to outcome of radiotherapy, as assessed by an independent observer 6 months later according to predefined criteria. RESULTS: T2 relaxation times of the eight EOM were longer in GO patients than in controls: median [range] 126 [52--250] vs. 88 [50--126] msec; P = 0.003. Per subject the single eye muscle with the longest T2 time was selected to represent active inflammation (excluding the lateral muscles for technical reasons). Again patients were different from controls: 160 [68--250] vs. 103 [86- 115] msec, P < 0.001. In the group of 34 responders to subsequent radiotherapy, these T2 times tended to be longer than in the 30 nonresponding patients: 168 [108--250] vs. 138 [68--216] msec, P = 0.07. Using a cut-off value of 130 msec (derived from a receiver-operator-characteristics curve) a positive predictive value of 64% and a negative predictive value of 92% for the outcome of radiotherapy was calculated. CONCLUSION: Quantitative orbital magnetic resonance imaging was found to be less accurate in predicting successful outcome of radiotherapy than expected. It seems more useful in detecting the fibrotic end stage than the active stage of Graves' ophthalmopathy. It is therefore of limited use in the decision whether or not to apply immunosuppression in patients with moderately severe Graves' ophthalmopathy. PMID- 11207636 TI - Autoimmune polyendocrine syndrome type 1 (APS I) in Norway. AB - OBJECTIVE: The aim of the present study was to investigate Norwegian patients with autoimmune polyendocrine syndrome type I (APS I), with respect to occurrence and clinical presentation, reactivity towards different autoantigenes and mutations in the autoimmune regulator (AIRE) gene. PATIENTS: Twenty Norwegian patients from 15 families with APS I (11 males, nine females; mean age 26 years, range 4--54) were included by contacting all major hospitals in Norway. METHODS: Clinical data was collected from both patients and their physicians by the use of questionnaires and patient records. Autoantibodies were analysed using radioimmunoassays based on antigen synthesized by in vitro transcription and translation. AIRE mutations were determined by DNA sequence analysis. RESULTS: The prevalence of APS I in Norway was estimated to be about 1 : 80,000 individuals. We found about the same distribution of disease characteristics as has been reported in Finnish patients. The diagnosis was delayed in many individuals. In two thirds of the cases, the patients were admitted in Hospital with acute adrenal insufficiency or hypocalcaemic crisis. Forty percent of these patients already had one of the main disease manifestations. Four different mutations in the AIRE gene were found in the Norwegian cohort. A 13-bp deletion in exon 8 (1085--1097(del)) was the most frequent mutation, present in 22/40 (55%) of the alleles. Eighty-five percent of the patients had either autoantibodies against 21 hydroxylase or aromatic L-amino acid decarboxylase. Five of eight women (age > 13 years) had ovarian failure, and all of these had antibodies against side-chain cleavage enzyme (P = 0.0002). CONCLUSION: Norwegian patients with APS I clinically resemble patients from Finland and other European countries. The diagnosis APS I must be considered in children and adolescents with chronic mucocutaneous candidiasis, autoimmune adrenocortical failure or hypoparathyroidism in order to avoid fatal complications. Analysis of autoantibodies and mutational analysis of the AIRE gene are valuable diagnostic tools, especially in the early stages of the disease. PMID- 11207637 TI - Effect of vitamin K and/or D on undercarboxylated and intact osteocalcin in osteoporotic patients with vertebral or hip fractures. AB - OBJECTIVE: To examine serum undercarboxylated osteocalcin (OC) with application of an ELISA in normal women and in osteoporotic patients with vertebral fractures or hip fractures, and to investigate the effects of vitamin K and/or D treatment on undercarboxylated OC and intact OC in vertebral fractures. PATIENTS: They were 43 premenopausal (PRE) and 48 postmenopausal healthy females (POST), 89 osteoporotic patients with vertebral fractures (VX) and, 24 patients with hip fracture (HX). MEASUREMENTS: Intact OC was measured by an IRMA and undercarboxylated OC was measured by an ELISA. RESULTS: Intact osteocalcin was significantly higher in POST and VX than in PRE, and was significantly lower in HX than in POST and VX. Undercarboxylated OC tended to be higher in POST, VX and HX than in PRE, but not significantly. The ratio of undercarboxylated OC to intact OC was significantly higher in HX than in POST and in VX. After 4 weeks treatment with K, D, and K + D to 56 VX, undercarboxylated OC decreased significantly in the groups with K and K + D. Intact OC tended to increase slightly in the groups given K, D, K + D, but not significantly so. Vitamin K and vitamin K + D markedly decreased the ratio of undercarboxylated/intact OC to approximately 80%. On the other hand, vitamin D did not decrease that ratio. CONCLUSIONS: There was a disproportion of undercarboxylated osteocalcin to intact osteocalcin between postmenopausal women and osteoporotic patients with vertebral fractures or hip fractures. Vitamin K did decrease undercarboxylated osteocalcin, vitamin D did not change undercarboxylated osteocalcin, and vitamin D did not enhance the effect of vitamin K on undercarboxylated osteocalcin. PMID- 11207638 TI - Serum leptin levels are higher but are not independently associated with severity or mortality in the multiple organ dysfunction/systemic inflammatory response syndrome: a matched case control and a longitudinal study. AB - OBJECTIVE: Hypercatabolism and immune dysfunction are closely associated with the development of systemic inflammatory response--multiple organ dysfunction (SIRS/MODS) in critical illness. It remains unclear however, whether leptin, an adipocyte-derived hormone whose levels are influenced by several cytokines and which regulates immune function, food-intake and energy expenditure is independently related to the development of and/or severity and mortality from SIRS/MODS. DESIGN AND PATIENTS: To assess the role of leptin in SIRS/MODS we performed a matched case control and a longitudinal study (14 days) in 35 critically ill patients with SIRS/MODS and 35 matched controls. RESULTS: Baseline leptin levels were positively associated with body mass index (BMI) and TNF-alpha (P < 0.01) in patients and with IGF-1 and IL-6 levels (P < 0.05) in controls. Furthermore, leptin levels exhibited a progressive increase from the first to the last day of the study and although baseline levels were not different, peak leptin levels as well as leptin levels on the last day of the study were significantly higher in cases than in controls (P < 0.05). TNF-alpha levels, IL-6 and cortisol levels were also higher, whereas IGF-1 levels were lower in cases (P < 0.05). To assess whether leptin levels are independently associated with SIRS/MODS we performed multivariate logistic regression analysis which revealed that leptin up-regulation in cases is mediated by elevated TNF-alpha and cortisol levels. Finally, there was no independent association between leptin and survival in this group of critically ill patients. CONCLUSION: We conclude that cytokines and cortisol upregulate leptin levels, which may contribute to the development of the hypercatabolism, wasting and immune dysfunction but leptin levels are not independently associated with severity or mortality of patients with systemic inflammatory response-multiple organ dysfunction. PMID- 11207639 TI - Growth restriction in dexamethasone-treated preterm infants may be mediated by reduced IGF-I and IGFBP-3 plasma concentrations. AB - OBJECTIVE: Preterm infants receiving dexamethasone for respiratory morbidity frequently suffer restricted growth. The aim of this study was to investigate the interactions between dexamethasone treatment regimen and circulating IGFBP-3 and IGF-I levels, and the associations between these variables and linear growth rate in preterm babies receiving dexamethasone for chronic lung disease of prematurity. DESIGN: A randomised, unblinded, clinical trial of two different courses of dexamethasone: a 42-day tapering course (the long course) and a repeatable 3 day pulse course. PATIENTS: Forty preterm infants (19 in the pulse group, 21 in the long group) with a birthweight < or = 1250 g who were ventilated at 7 days of age. MEASUREMENTS: Lower leg length was measured thrice weekly by knemometry, and IGFBP-3 and IGF-I levels were measured prior to commencing treatment, at 14 and 42 days of treatment and at 36 weeks postmenstrual age (PMA). Interactions between variables were analysed by stepwise regression analysis and analysis of covariance (ANCOVA). Associations between variables were assessed by correlation coefficients. RESULTS: In an ANCOVA, mean daily dose of dexamethasone/kg (MDDD) and treatment group both significantly influenced IGFBP-3 levels (P = 0.0009 and P = 0.017, respectively), and tended to influence IGF-I levels similarly (P = 0.098 and P = 0.07). MDDD also significantly influenced mean daily increase in lower leg length (MDILL; P < 0.01). IGFBP-3 and IGF-I levels were significantly related to MDILL (ANCOVA: P < 0.01). The correlation coefficients for IGFBP-3 and IGF-I levels and MDILL were 0.2 and 0.3 (both P < 0.0001), respectively. IGFBP-3 and IGF-I levels were highly correlated (r(2) = 0.52, P < 0.0001) and both increased significantly with increasing PMA (P < 0.0001). IGF-I levels were higher in females (P = 0.036). CONCLUSION: This study provides evidence that the growth-restricting effects of dexamethasone may be mediated, at least in part, via suppression of the IGF axis. Both dexamethasone dose and treatment regimen influence circulating IGF-I and IGFBP-3 levels, and both are important in inducing growth restriction. PMID- 11207640 TI - Carbohydrate metabolism during long-term growth hormone treatment in children with short stature born small for gestational age. AB - OBJECTIVE: To assess possible side-effects of long-term continuous growth hormone (GH) treatment on carbohydrate (CH) metabolism in children with short stature born small for gestational age. DESIGN: In a prospective, randomised double blind, dose-response multicentre trial, the effect of GH treatment on CH metabolism was evaluated, comparing two GH dosages [3 vs. 6 IU/(m(2) body surface.day)]. PATIENTS: Seventy-eight children with short stature (height SD score < - 1.88) born small for gestational age (birth length SD-score < - 1.88) being all prepubertal with a mean (SD) chronological age of 7.3 (2.2) years before start of treatment. MEASUREMENTS: Glucose and insulin concentrations during oral glucose tolerance tests (OGTTs) and glycosylated haemoglobin (HbA(1c)) were measured before and during 6 years of GH treatment. RESULTS: Before treatment, the glucose response to oral glucose after 120 min was in six of the 78 children (8%) above 7.8 mmol/l but below 11.1 mmol/l, indicating impaired glucose tolerance (IGT), whereas after 6 years of GH treatment, IGT was found in 4% of the children. None of the children developed diabetes mellitus. Mean fasting glucose levels had increased significantly by 0.5 mmol/l after 1 year of GH treatment, without a further increase thereafter. The 2-h area under the curve adjusted for fasting levels (AUCab) for glucose and the HbA(1c) levels were lower after 6 years of GH treatment compared to baseline. During GH treatment, all HbA(1c) levels were in the normal range. In contrast to the effects on glucose levels, GH treatment induced considerably higher fasting insulin levels and glucose-stimulated insulin levels. The increase in AUCab for insulin occurred particularly during the first year of treatment, whereas the fasting insulin levels showed a further increase from one to six years. As a result, the 30- and 120-min ratios of insulin to glucose were higher during GH treatment compared to the start of treatment. The children who remained prepubertal during the entire study period showed similar patterns in glucose and insulin levels compared to the children who entered puberty. None of the observed changes were different between the GH dosage groups. CONCLUSIONS: Continuous GH treatment during 6 years in children with short stature born small for gestational age has no adverse effects on glucose levels, even with dosages up to 6 IU/(m(2) d). However, as has been reported in other patient groups, GH treatment induces higher fasting insulin levels and glucose-stimulated insulin levels, indicating relative insulin resistance. Since the consequences of long term hyperinsulinism during childhood are unknown, careful follow-up of these GH treated children born small for gestational age is required. PMID- 11207641 TI - Novel application of IGF-I and IGFBP-3 generation tests in the diagnosis of growth hormone axis disturbances in children with beta-thalassaemia. AB - OBJECTIVE: Children with beta-thalassaemia major (beta-thal) frequently have growth retardation in the presence of low serum IGF-I and a normal GH response to pharmacological stimulation suggesting that they have GH insensitivity (GHIS). This study was carried out to study the cause of their growth retardation. DESIGN: We studied IGF-I and IGFBP-3 generation after exogenous GH administration for four days, in 15 prepubertal controls (C) and 41 prepubertal beta-thal patients divided into three groups according to their growth status: (Group 1) 15 with normal growth (N-thal) (Group 2) 16 with decelerated growth (D-thal) and (Group 3) 10 with short stature (S-thal), in order to determine whether GHIS is the cause of their growth retardation. MEASUREMENTS: IGF-I and IGFBP-3 were measured daily, before and for 4 days after daily administration of 0.1 IU/kg hGH, in 3 groups of prepubertal beta-thal patients and normal controls. RESULTS: N-thal and C had similar basal serum IGF-I (142 +/- 52 and 196 +/- 56 ng/ml, respectively) and IGFBP-3 concentrations (2.07 +/- 0.49 and 2.66 +/- 0.41 mg/l, respectively) as well as a similar percent increase of IGF-I (101 +/- 23% and 104 +/- 37%, respectively) and IGFBP-3 (52 +/- 36%, and 38 +/- 14%, respectively) during the generation tests. S-thal and D-thal had significantly lower basal IGF I and IGFBP-3 concentrations (85 +/- 42 and 101 +/- 36 ng/ml; and 1.60 +/- 0.49 and 1.79 +/- 0.52 mg/l, respectively) as compared to N-thal and C (P < 0.001 and P < 0.005, respectively), and a significantly higher percent increase of IGF-I and IGFBP-3 during the generation tests (249 +/- 43 and 161 +/- 76%; and 121 +/- 99 and 73 +/- 35%, respectively) as compared to N-thal and C (P < 0.0001 and P < 0.01, respectively). Twenty-five percent of the growth retarded patients had classic GH deficiency (GHD) and percent increases of IGF-I and IGFBP-3 in the generation tests (164 +/- 86% and 80 +/- 49%, respectively) which were similar to those of the remaining growth-retarded children. CONCLUSION: The greater percent increases of IGF-I and IGFBP-3 in the generation tests of the growth retarded beta-thal patients, both with and without GHD, strongly suggest impaired GH secretion rather than GHIS as the cause of their growth retardation. We conclude that the IGF-I and IGFBP-3 generation tests are useful tools for the study not only of GHIS but also of GH secretory disorders in patients with beta-thal and short stature that can easily be performed in an outpatient setting as an initial test to identify the patients that may benefit from GH therapy. PMID- 11207642 TI - Effect of exogenous melatonin on vascular reactivity and nitric oxide in postmenopausal women: role of hormone replacement therapy. AB - OBJECTIVE: Several effects of melatonin are modulated by gonadal steroids and are reduced in ageing women. Administration of melatonin reduces internal carotid artery pulsatility index (PI), and blood pressure in young individuals. Whether these effects are conserved in postmenopausal women and are influenced by hormone replacement therapy (HRT), was herein investigated. DESIGN: Randomised, double blind placebo controlled study. PATIENTS: Twenty-three postmenopausal women of which 11 were unreplaced with HRT and 12 on the oestrogenic phase of continuous transdermal estradiol (50 microg/day) plus cyclic medroxyprogesterone acetate (5 mg/day x 12 days every 28 days). MEASUREMENTS: Internal carotid PI, by colour Doppler, and supine blood pressure were evaluated 90, 180 and 240 minutes following the oral administration of melatonin (1 mg) or placebo. Levels of nitrites/nitrates (NOx), the stable derivatives of nitric oxide, were also evaluated in samples collected 90 minutes following the administration of placebo or melatonin. RESULTS: In women not on replacement therapy melatonin was ineffective. In HRT-treated women, melatonin reduced internal carotid artery PI (P = 0.005). The effect was maximal within 90 minutes, and maintained for at least 240 minutes, with melatonin levels in the nocturnal physiological range. Systolic and diastolic blood pressures were reduced of 8 mmHg (P = 0.038) and 4 mmHg (P = 0.045), respectively, while NOx levels were significantly increased (P = 0.024). CONCLUSIONS: The circulatory response to melatonin is conserved in postmenopausal women with but not without hormone replacement therapy. Maintenance of the cardiovascular response to melatonin, may be implicated in the reduced cardiovascular risk of postmenopausal women with hormone replacement therapy. PMID- 11207643 TI - Hydrocortisone replacement dosage influences intraocular pressure in patients with primary and secondary hypocortisolism. AB - BACKGROUND: It has been suggested that the variation of intraocular pressure (IOP) during the day follows the diurnal variation of serum cortisol. There is also a higher risk of ocular hypertension and glaucoma in patients taking excessive oral steroid treatment. We assessed whether different replacement doses of hydrocortisone (HC) influenced IOP. METHODS: Seventeen patients (six Addison's disease, 11 hypopituitarism; seven males) aged 24-58 years mean 42.7 years and 20 control subjects (nine males) aged 20--59 years mean 38.7 years were studied. On the first visit, the 17 patients had been taking HC replacement doses, 20 mg morning and 10 mg afternoon. Serum cortisol and IOP in both eyes (Goldmann applanation tonometer) were measured at 0900, 1100, 1300, 1500, 1700 hours with HC 20 mg taken after the 0900 h assessment. The dose of HC was then reduced to 10 mg morning and 10 mg afternoon for 1 week and the measurements were repeated in 16 patients, with HC 10 mg taken at 0900 h. RESULTS: In the patients the peak serum cortisol occurred at 1100 h after the 0900 h HC dose. Cortisol levels were significantly higher at 1100, 1300, 1500 and 1700 h after taking 20 mg compared to 10 mg HC. The mean (SEM) IOP (mmHg) was significantly higher after 20 mg HC compared with 10 mg HC at 1300 h: 14.7(0.6) v 13.1(0.6) (P = 0.004) and at 1500 h: 14.4(0.6) v 13.1(0.5) (P = 0.04). The total mean (SEM) daily IOP score was significantly higher after 20 mg HC compared with 10 mg HC: 14.5(0.3) v 13.5(0.3) (P = 0.0002). The total mean (SEM) daily IOP score after the 20 mg HC dose compared with the control subjects was: 14.5(0.3) v 13.7(0.3) (P = 0.08). CONCLUSION: Intraocular pressures during the day are influenced by the morning hydrocortisone replacement dosage with significantly higher intraocular pressure levels in the early afternoon following 20 mg compared with 10 mg. A morning hydrocortisone dose of 10 mg leads to a more physiological intraocular pressure profile during the day. These data support the view that a daily replacement dose of 30 mg hydrocortisone may be excessive. PMID- 11207644 TI - Panhypopituitarism associated with severe retroperitoneal fibrosis. AB - A 43-year-old man, with a history of central diabetes insipidus diagnosed 3 years previously, complained about reduced libido. An MRI scan showed a suprasellar lesion just below the supraoptic recess of the third ventricle. A stereotactically guided biopsy revealed fibrous glia, but no other specific tissue and no inflammatory cells. Two months later the patient presented with fatigue and muscular weakness. Tertiary adrenal failure and hypothyroidism were diagnosed by endocrine function tests and therapy with levothyroxine and hydrocortisone was started. Another 2 months later the patient was admitted with giddiness, nausea, peripheral oedema and oliguria. Radiological imaging and an open transperitoneal kidney exploration showed severe fibrosis around both ureters. Histological examination confirmed the diagnosis of idiopathic retroperitoneal fibrosis. Presumably the suprasellar tumour was the first manifestation of retroperitoneal fibrosis. Once the diagnosis 'idiopathic retroperitoneal fibrosis' is confirmed, fibrotic manifestations and complications involving extra-retroperitoneal tissues including the endocrine system, should be sought. PMID- 11207645 TI - Recurrent ACTH-independent Cushing's syndrome in multiple pregnancies and its treatment with metyrapone. AB - A 17-year-old primigravid woman presented with Cushing's syndrome. Typical clinical symptoms and signs developed at the beginning of pregnancy. By week 17 of gestation, plasma cortisol diurnal rhythm was absent and there was a paradoxical increase in plasma cortisol after a 1-mg dexamethasone overnight suppression test. Basal urinary free cortisol was 10 times above the upper limit (in pregnancy) and ACTH levels were suppressed. The diagnosis of ACTH- independent Cushing's syndrome was established. MRI scans revealed normal adrenal and pituitary glands. To control hypercortisolism, the patient was treated with metyrapone. At 34 weeks of gestation, the patient developed preeclampsia and underwent caesarean section. A female infant weighing 1070 g was delivered. No apparent metyrapone-induced teratogenic effects were observed. Cushing's syndrome in the patient resolved within three weeks of delivery. No corticosteroid replacement therapy either for child or mother was needed. Eight months after delivery the patient became pregnant again and rapidly developed Cushing's syndrome with typical clinical symptoms and signs and laboratory results (urinary free cortisol 6464 nmol/24 h). This second pregnancy was unwanted and terminated by artificial abortion that was followed by rapid resolution of hypercortisolism. A third pregnancy, 12 months after delivery was also accompanied by the rapid development of hypercortisolism which recovered after artificial termination. The mechanisms by which pregnancy-induced Cushing's syndrome occurred in this patient are unclear. Aberrant responsiveness or hyperresponsiveness of adrenocortical cells to a non-ACTH and non-CRH substance produced in excess in pregnancy should be considered. Metyrapone suppression of hypercortisolism currently represents the best treatment for these rare cases. PMID- 11207646 TI - Apoptosis signals in atopy and asthma measured with cDNA arrays. AB - A variety of studies have stressed the importance of the control of inflammatory cell longevity and the balance of pro-survival and pro-apoptotic signalling. Recently, asthma was found to be associated with reduced apoptosis of inflammatory cells in lung tissue. The aim of the study was to investigate the systemic activation of apoptosis pathways using cDNA array technology in atopy and asthma. Eighteen atopic asthmatics (AA), eight atopic non-asthmatic (AN) and 14 healthy control subjects (C) were included in the study. Peripheral blood mononuclear cells were separated with gradient centrifugation, mRNA purified and the reverse-transcribed probes hybridized to cDNA arrays. The signals were compared by standardizing to the 100 most expressed genes and group differences assessed with the Mann-Whitney U-test. We found a concerted up-regulation of several pro-survival cytokines and growth factors in AN and AA. FAS and FASL were not differentially expressed, but FAST kinase was over-expressed in AN and AA. The tumour necrosis factor pathway was activated in AN and AA with increased cytokine and receptor levels and increased TRAF2, an intracellular signalling product. There were indications of a down-regulated p53 system. In contrast, the Bcl-2 family of genes showed a net pro-apoptotic profile in AN and AA. The group of caspases showed a constant gene expression pattern in all groups. In conclusion, significant differences in the expression of apoptosis-related genes were found in peripheral blood of atopic individuals with and without asthma. cDNA array technology proved to be useful and may be complementary to DNA-based studies in order to analyse interactive and multidimensional pathways as shown here for apoptosis. PMID- 11207647 TI - Tears contain the complement regulator CD59 as well as decay-accelerating factor (DAF). AB - Previous studies have shown that DAF (or CD55), a cell surface inhibitor of autologous C3 activation, is present in tears and that > 90% of the C3 convertase regulatory activity in tear fluid resides in this protein (Lass JH et al., Invest Ophth Vis Sci 1990; 31:1136-48). This study investigated whether (i) the membrane cofactor protein (MCP or CD46), an additional factor that regulates C3 activation, and (ii) the membrane inhibitor of reactive lysis (MIRL or CD59), a cell surface regulator that acts to prevent formation of the membrane attack complex, are also present in tears, and if so, are functional. Two-site immunoradiometric assays showed that MCP is present in tears at low levels (42 + 8 ng/ml, n = 8) while CD59 is present at levels (222 + 78 ng/ml, n = 14) comparable to those of DAF (325 + 289 ng/ml, n = 12). The concentrations of CD59 (i) were increased two-fold or more in closed eye tears, and (ii) were decreased in reflex tears. Western blotting showed that CD59 protein in tears migrates with an apparent mol. wt similar to membrane CD59 protein. Phenyl-Sepharose adsorption and Triton X-114 partitioning of tear CD59 as well as of tear DAF however, showed that both proteins are devoid of GPI anchors. Assays using cobra venom factor activated human serum and guinea pig erythrocytes showed that CD59 is functionally active in inhibiting autologous C5b-9-mediated lysis and, under constitutive conditions, accounts for > 85% of the C9 inhibitory activity in tear fluid. PMID- 11207648 TI - Immune complex processing in C1q-deficient mice. AB - Complement and Fcgamma receptors are known to mediate the processing of immune complexes (IC), and abnormalities in these mechanisms may predispose to the development of lupus. We explored the processing of IC in mice deficient in complement component C1q. 125I-labelled IC comprising Hepatitis B surface antigen (HBsAg)/human anti-HBsAg (HBsAg/Ab) were injected intravenously and the sites of IC clearance determined by direct counting of organ uptake at various time points. The liver and spleen were the main sites of IC uptake in all mice. The splenic uptake of IC was significantly reduced in the C1q-deficient mice compared with the control mice. C1q-deficient mice also exhibited an initial accelerated hepatic uptake of IC similar to that seen in human subjects with hypocomplementaemia. The hepatic localization of IC at later time points was similar in both groups of mice. These data in mice are consistent with previous observations in humans that confirm that the classical pathway of complement plays an important role in the appropriate processing of IC in vivo. PMID- 11207649 TI - Expression of IL-18 by Mycobacterium avium-infected human monocytes; association with M. avium virulence. AB - Disseminated Mycobacterium avium infection is the most frequent bacterial infection in patients with advanced AIDS and also associated with interferon gamma (IFN-gamma) or IL-12 receptor deficiency. IFN-gamma is a key cytokine in host defence against M. avium infection. Expression of IL-18, a potent IFN-gamma inducer, and IFN-gamma by human monocytes after infection with M. avium was examined. Monocytes were co-cultured with isogenic smooth-transparent (SmT: virulent) or smooth-domed (SmD: avirulent) M. avium strains (10 organisms per monocyte). Infection with the SmD strain induced significantly higher concentration of IL-18 and IFN-gamma in culture supernatants than did the SmT strain. IFN-gamma production in response to M. avium was partially inhibited by anti-human IL-18 MoAb. Both recombinant human IL-12 (77 +/- 42 pg/ml, control versus 1492 +/- 141 pg/ml, cultures with IL-12 1 ng/ml) and IL-18 (126 +/- 37 pg/ml, control versus 2683 +/- 864 pg/ml, cultures with IL-18 10 ng/ml) augmented M. avium-induced IFN-gamma production. Freshly isolated uninfected monocytes expressed constitutive levels of IL-18. Following infection with M. avium, enhancement of IL-18 mRNA expression peaked at 3-6 h. IL-18 protein was detected in monocyte lysates as early as 1 h after infection with both SmT and SmD M. avium strains by Western blotting. Higher IL-18 expression by monocytes infected with the avirulent strain may result in more IFN-gamma production, thus modulating its pathogenicity. Local induction of IL-18 may be important both for M. avium pathogenicity and host defence and become a potential candidate for immunotherapy. PMID- 11207650 TI - Opsonizing antibodies (IgG1) up-regulate monocyte proinflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and IL-6 but not anti-inflammatory cytokine IL-10 in mycobacterial antigen-stimulated monocytes-implications for pathogenesis. AB - Cachexia is one of the prominent features of advanced tuberculosis (TB) seen in association with increased expression of the monokine TNF-alpha. Several mycobacterial proteins, including PPD, stimulate TNF-alpha secretion from monocytes. Host factors that may play a role in cytokine expression from monocytes remain largely unknown. One such factor is the opsonizing antibodies. Monocytes have high-affinity receptors (FcgammaI and FcgammaIII) for IgG1 and IgG3 antibodies that mediate antigen uptake. We have reported selective up regulation of IgG1 (which bind to Fcgamma receptors) in advanced TB and have recently shown the ability of PPD-specific IgG1 antibodies to augment TNF-alpha expression in PPD-stimulated monocytes. These observations have now been extended to other cytokines with semipurified fractions from secreted antigens of Mycobacterium tuberculosis (containing 30 kD and 58 kD) that were devoid of lipids, glycolipids and carbohydrates. In the presence of heat-inactivated TB plasma containing known amounts of antigen-specific IgG1 antibodies, these fractions induced significantly increased TNF-alpha, IL-6 and IL-10 secretion. Absorption of IgG1 with Protein 'A' removed the augmenting activity for TNF-alpha and IL-6 secretion from the TB plasma samples. In the case of IL-10, removal of IgG1 resulted in increased rather than decreased IL-10 secretion. These results suggest a possible pathogenic role for antibodies in TB by enhancing proinflammatory and blocking down-regulatory cytokines such as IL-10 cytokines during the chronic phase of TB. PMID- 11207651 TI - Effect of deworming on human T cell responses to mycobacterial antigens in helminth-exposed individuals before and after bacille Calmette-Guerin (BCG) vaccination. AB - The protective efficacy of BCG vaccination against pulmonary tuberculosis (TB) is highly variable in different populations. The reason remains to be elucidated. This study aims to investigate the possible effect of intestinal helminths on the immune response to PPD in naturally immunized or BCG-vaccinated humans. The study population was assessed for helminthic infection and those found to be positive were randomly assigned to either an albendazole treatment group or a control group who received a placebo. The immune response to PPD was compared between the two groups. In addition, subjects who were tuberculin skin test-negative in both groups were BCG vaccinated and later on tested for PPD-specific responses. Albendazole induced elimination/or reduction in intestinal worms resulting in a significant improvement in T cell proliferation and in interferon-gamma production by peripheral blood mononuclear cells (PBMC) stimulated with PPD. Moreover, BCG vaccination significantly improved PPD-specific immune responses in the treated group but not in the placebo group. The differences in the in vivo skin test responses were not significant. The data show that cellular immune responses to PPD are reduced in persons with concurrent helminthic infections, perhaps reflecting a lowered resistance to mycobacterial infections. This could explain, at least in part, the reduced efficacy of BCG against TB in helminth endemic areas of the world. PMID- 11207652 TI - Epitope focus, clonal composition and Th1 phenotype of the human CD4 response to the secretory mycobacterial antigen Ag85. AB - Lymphoproliferation of healthy donors was tested against mycobacterial antigens (PPD, Ag85, Ag85 peptides). All PPD responders recognized the secretory antigen Ag85 and the peptide specificity for Ag85B was defined. Peptide 91-108 was recognized by 85% of donors. In addition, all CD4 T cell lines generated from 12 donors against PPD or Ag85 responded to 91-108. When this peptide was used to generate T cell lines, the cells responded also to tuberculins from atypical mycobacterial species. Thus the cross-reactive peptide behaved as quasi universal. The analysis of TCR-BV gene usage by cell lines showed that most Ag85 specific T cells correspond to 91-108-specific clonotypes. Intracytoplasmic staining of cell lines after phorbol myristate acetate stimulation resulted in dominance of interferon-gamma (IFN-gamma)-IL-4 double-positive cells, whereas antigen stimulation resulted in production of IFN-gamma only. The data show that peptide 91-108 is the major focus of the CD4 response to mycobacterial antigens in peripheral blood mononuclear cells and in T cell lines from PPD responders. PMID- 11207654 TI - The impact of CMV on the respiratory burst of macrophages in response to Pneumocystis carinii. AB - Infection of human monocyte-derived macrophages with CMV decreased the respiratory burst when cells were stimulated with opsonized zymosan or Pneumocystis carinii (P. carinii). Such an effect, though smaller, was also seen with heat-inactivated CMV, but only when triggered by zymosan. The effect was most pronounced in cells obtained from CMV antibody-negative donors. Dexamethasone further reduced the respiratory burst, both in uninfected and CMV infected cells. Interferon-gamma increased the response in uninfected cells and, to a lesser extend, in cells treated with heat-inactivated CMV, whereas no effect was seen with infective CMV. No overt productive infection or cytopathology could be detected, however, the monocytes incubated with infective but also heat inactivated CMV formed clusters, a phenomenon that was equally pronounced in cultures from CMV antibody positive and negative-donors. These results might help explain the worse prognosis of P. carinii pneumonia in patients coinfected with CMV and receiving dexamethasone. PMID- 11207653 TI - Impact of tuberculosis (TB) on HIV-1 activity in dually infected patients. AB - Active TB in HIV-1-infected subjects is associated with increased HIV-1-related immunodeficiency and mortality. We assessed plasma viral load in HIV-1-infected patients with pulmonary TB (HIV/TB) and non-TB symptomatic HIV-1-infected patients (HIV). HIV-1 load was higher in HIV/TB compared with HIV at higher CD4 counts (> 500/microl) (P < 0.01), but not at lower CD4 counts (< 500/microl). We also evaluated the status of HIV-1 gene expression in peripheral blood mononuclear cells (PBMC) and serum from HIV/TB and CD4-matched healthy HIV infected patients (HIV/C) by reverse transcriptase-polymerase chain reaction over a range of CD4 (> 900/microl to < 200/microl). HIV-1 RNA in serum and PBMC correlated to one another, and both were markedly higher in HIV/TB compared with HIV/C with higher CD4 counts. Also, during a longitudinal study of anti tuberculous chemoprophylaxis in HIV-1-infected patients, 10 subjects who developed TB had serologies before, at the time, and after the diagnosis of TB. These HIV/TB patients had an increase in viral load (average 2.5-fold) at the time of diagnosis of TB (P < 0.05). Overall, these data indicate that the transcriptional activity of HIV-1 is enhanced in HIV-1-infected patients with active TB, especially during early HIV-1 disease. As TB often is an early HIV-1 opportunistic infection, it may particularly favour early viral replication and dissemination, and therefore contribute to progression of HIV-1 disease. PMID- 11207655 TI - Characterization of the cellular immune function of patients with chronic mucocutaneous candidiasis. AB - Chronic mucocutaneous candidiasis (CMC) is a rare syndrome characterized by persistent and refractory infections of the skin, nails and mucosal tissues by yeasts of the genus Candida. Defects in the cellular limb of the immune system are well documented in CMC patients, but non-specific immune defects, such as myeloperoxidase deficiency or phagocyte chemotaxis disorders, have also been described. Nonetheless, the underlying defect(s) remains poorly understood, and further studies are required. We studied eight CMC patients without endocrinopathies, who showed (i) low normal proliferative response to phytohaemagglutinin (PHA), (ii) partially defective response to pokeweed mitogen (PWM), and (iii) impaired response to Candida and PPD antigens. Furthermore, peripheral blood mononuclear cells (PBMC) from CMC patients produced lower levels of type-1 cytokines (IL-2 and interferon-gamma) in response to Candida antigens, compared with control individuals. Conversely, we did not observe an enhancement of IL-4 and IL-10 in the patients, suggesting that, even though Th1 cytokines are decreased, the Th2 response is not increased in CMC. Nevertheless, the synthesis of these cytokines was normal when induced by PHA. We also observed an increased antigen-induced apoptosis in lymphocytes from the patients compared with controls, and this applied both to Candida and PPD antigens. Lastly, innate immunity defects were investigated. We observed an impairment of natural killer activity against K-562 target cells in half of the studied patients. These findings corroborate the extensive clinical and laboratory variability of CMC, which requires further studies on a larger number of patients to be better understood. PMID- 11207656 TI - Accelerated calcium influx and hyperactivation of neutrophils in chronic granulomatous disease. AB - The relationship between activation of NADPH-oxidase, alterations in membrane potential and triggering of Ca2+ fluxes in human phagocytes has been investigated using neutrophils from four subjects with chronic granulomatous disease (CGD). Cytosolic Ca2+ and membrane potential were measured by spectrofluorimetry, and net efflux and influx of Ca2+ by radiometric procedures. Exposure of normal neutrophils to the chemotactic tripeptide, N-formyl-L-methionyl-L-leucyl-L phenylalanine (FMLP; 1 microM) was accompanied by an abrupt increase in cytosolic Ca2+ coincident with membrane depolarization and efflux of the cation. These events terminated at around 30 s after the addition of FMLP and were followed by membrane repolarization and store-operated influx of Ca2+, both of which were superimposable and complete after about 5 min. Activation of CGD neutrophils was also accompanied by an increase in cytosolic Ca2+, which, in spite of an efficient efflux response, was prolonged in relation to that observed in normal cells. This prolonged increase in cytosolic Ca2+ in activated CGD neutrophils occurred in the setting of trivial membrane depolarization and accelerated influx of Ca2+, and was associated with hyperactivity of the cells according to excessive release of elastase and increased activity of phospholipase A2. Treatment of CGD neutrophils with the type 4 phosphodiesterase inhibitor, rolipram (1 microM) restored Ca2+ homeostasis and attenuated the increase in elastase release. These findings support the involvement of NADPH-oxidase in regulating membrane potential and Ca2+ influx in activated neutrophils, and may explain the disordered inflammatory responses and granuloma formation which are characteristic of CGD. PMID- 11207657 TI - Recombinant bacille Calmette-Guerin (BCG) expressing human interferon-alpha 2B demonstrates enhanced immunogenicity. AB - To increase its immunostimulatory properties, BCG was genetically engineered to secrete recombinant human interferon-alpha 2B (rhIFN-alpha) under control of the mycobacterial heat shock protein (hsp)60 promoter and the alpha antigen signal sequence. Expression of rhIFN-alpha was readily detectable by ELISA and on Western blotting. When compared with control BCG, rhIFN-alpha BCG was substantially more active in inducing the production of IFN-gamma and IFN inducible protein 10 (IP-10) from human peripheral blood mononuclear cells, while IL-10 production was correspondingly decreased. These effects were reversible upon antibody neutralization of rhIFN-alpha. Among 10 patients tested, rhIFN alpha BCG enhanced IFN-gamma production in all patients ranging from 1.4- to 23.7 fold with a general trend toward greatest enhancement among those with weakest baseline responses to control BCG. Correspondingly, rhIFN-alpha BCG decreased IL 10 production in all patients by 1.2-4.8-fold. The onset of IFN-gamma production induced by rhIFN-alpha BCG was also more rapid, occurring within 4 h after stimulation versus > 24 h with wild-type BCG. The observation that the maximum IFN-gamma induction depends on the simultaneous presence of both IFN-alpha and BCG highlights the advantages of rhIFN-alpha BCG. Taken together, these immunostimulatory properties of rhIFN-alpha BCG suggest that it may be a superior agent for immunotherapeutic protocols involving live BCG in humans. PMID- 11207658 TI - Increase of chemokine interferon-inducible protein-10 (IP-10) in the serum of patients with autoimmune liver diseases and increase of its mRNA expression in hepatocytes. AB - To clarify the role of IP-10 in autoimmune liver diseases, we studied the serum levels of IP-10 in 14 patients with autoimmune hepatitis (AIH), 23 patients with primary biliary cirrhosis (PBC), and 65 patients with chronic viral hepatitis (20 type B and 45 type C). The hepatic expression of IP-10 mRNA and the correlation between the serum levels of IP-10 and clinical parameters were also evaluated. In addition to 20 healthy controls, 16 rheumatoid arthritis (RA) patients were included as an extrahepatic inflammatory disease. The serum level of IP-10 was significantly (P < 0.02) higher in patients with AIH, PBC, and chronic hepatitis B and C than in healthy controls, and it was significantly correlated (P < 0.05) with the serum levels of aspartate aminotransferase and alanine aminotransferase in patients with AIH, PBC, and chronic hepatitis B and C. The serum level of IP 10 was not elevated in RA patients. After successful treatment of AIH and chronic hepatitis C, the serum level of IP-10 decreased to the same level as in healthy volunteers. As we previously showed in cases with chronic hepatitis B or C, in situ hybridization in both AIH and PBC cases demonstrated the expression of IP-10 mRNA in hepatocytes around focal or lobular necrosis surrounded by infiltrating mononuclear cells, whereas IP-10 mRNA was not expressed in areas around the damaged bile ducts in PBC cases. The present results suggest that IP-10 is specifically produced by hepatocytes in inflammatory areas irrespective of the aetiology of hepatitis, and that IP-10 may help to recruit T cells to the hepatic lesions in autoimmune liver diseases as well as in chronic viral hepatitis. PMID- 11207659 TI - Monocyte-derived dendritic cells: a potential target for therapy in multiple sclerosis (MS). AB - Monocytes can differentiate into dendritic cells (DC), cells with a pivotal role in both protective immunity and tolerance. Defects in the maturation or function of DC may be important in the development of autoimmune disease. We sought to establish if there were differences in the cytokine (granulocyte-macrophage colony-stimulating factor and IL-4)-driven maturation of monocytes to DC in patients with MS and whether drugs used to treat MS affected this process in vitro. We have demonstrated that there is no defect in the ability of magnetic activated cell sorting (MACS)-purified monocytes from patients with MS to differentiate to DC, but equally they show no tendency to acquire a DC phenotype without exogenous cytokines. Interferon-beta1a prevents the acquisition of a full DC phenotype as determined by light and electron microscopy and by flow cytometry. Methylprednisolone not only prevents the development of monocyte derived DC but totally redirects monocyte differentiation towards a macrophage phenotype. Evidence is evolving for a role for DC in central nervous system immunity, either within the brain or in cervical lymph nodes. The demonstrated effect of both drugs on monocyte differentiation may represent an important site for immune therapy in MS. PMID- 11207660 TI - The fine specificity of human T cell lines towards myelin basic protein peptides in southern Italian multiple sclerosis patients. AB - We studied the relationship between the HLA specificities associated with multiple sclerosis (MS) susceptibility in southern Italy and the reactivity of the human myelin basic protein (hMBP) immunogenic peptides 84-98 and 143-168, using short-term T-cell lines established from 9 MS patients and from 8 healthy individuals. In our population, DR15 was significantly associated with MS (34.9% in MS versus 13.7% in healthy controls, P < 0.05). This result is in agreement with the association found in northern Europe, but not with data obtained in a population from the island of Sardinia (Italy). In MS patients the frequency of reactive T-cell lines (TCL), tested for fine specificity against the immunodominant hMBP peptides 84-98 and 143-168, was increased for the hMBP 143 168 peptide (P < 0.05) but not for the 84-98 peptide. Although this reactivity was higher in DR15+ MS patients than in DR 15- MS patients, it seemed not to be associated with DR15 specificity in the MS population. Furthermore, there were no significant differences in frequency of reactive TCL to hMBP peptide 84-98 in DR15-positive or DR15-negative MS patients. Consequently, it appears that peptide 84-98, considered as a relevant autoantigen, is not implicated in the pathogenesis of MS in our population from southern Italy. PMID- 11207661 TI - Anti-inflammatory cytokine IL-10 and T cell cytokine profile in periodontitis granulation tissue. AB - Th2 cells are more abundant than Th1 cells in periodontitis lesions, but the relative importance of the Th1 and Th2 subsets in periodontal disease is not understood. In addition, the role of proinflammatory and anti-inflammatory cytokines in this disease process is unclear. Biopsies were obtained from 10 patients with early onset periodontitis (EOP) and 10 patients with adult periodontitis (AP). From all of the patients in the AP group we were able to obtain and section the gingival tissue to serve as controls. We used polyclonal monospecific antibodies to detect cells expressing IL-2, IL-4, IL-6, IL-10 and IL 15, tumour necrosis factor (TNF-alpha) and interferon-gamma (IFN-gamma) in formalin-fixed, paraffin-embedded sections of granulation tissue from periodontitis lesions. We also employed a series of oligonucleotide probes to detect cells expressing the cytokine transcripts in the same tissue biopsies. Cells that expressed IL-4 or IL-6 were more numerous than cells expressing either IL-2 or IFN-gamma. Th2 cells were more numerous in EOP and AP tissues. IL-15 substitutes for IL-2 in a number of biological activities related to the Th1 immune response, and interestingly, in periodontal lesions the IL-15-expressing cells outnumbered IL-2-expressing cells, suggesting that this is the pattern of immune regulation by T cells in the periodontium. The functional balance in the T cell subsets detected by their cytokine profiles underlies the importance of the anti-inflammatory mechanisms taking place in the diseased tissue. The numbers of inflammatory leucocytes that express the anti-inflammatory cytokine IL-10 are much more widely distributed than those that express the proinflammatory cytokines IL-6 and TNF-alpha. This study suggests that large numbers of infiltrating inflammatory cells as well as accessory cells are involved in the down-regulation of the inflammatory and immune response in periodontitis. PMID- 11207662 TI - Increase in tonsillar germinal centre B-1 cell numbers in IgA nephropathy (IgAN) patients and reduced susceptibility to Fas-mediated apoptosis. AB - IgAN is a common form of primary glomerulonephritis and also a disease of tonsillar focal infection. The comprehensive mechanism underlying this disease remains to be defined. To better understand its pathogenesis, we investigated tonsillar CD5+ B cells (B-1 cells) with respect to IgA synthesis. Germinal centre (GC) B cells were isolated from the tonsils of IgAN patients and the number of B 1 cells in the GC determined by flow cytometry. GC B-1 and B-2 (CD5- B) cells were purified by cell sorter, the cells were incubated with agonist anti-CD40 MoAb and the ability for antibody production by B-1 and B-2 cells determined by ELISPOT assay. GC B-1 cells and B-2 cells were incubated with agonist anti-Fas MoAb, and apoptosis in GC B-1 cells and B-2 cells was analysed by flow cytometry. Although B-1 cells do not usually take part in the GC reaction, an increase in B 1 cell numbers was observed in the GC of tonsils from IgAN patients. These B-1 cells were likely IgA1 antibody-producing cells, since the prominent IgA subclass in IgAN is generally considered to be IgA1. Although Fas-dependent apoptosis is essential for the elimination of activated B cells, these B-1 cells showed a reduced susceptibility to Fas-mediated apoptosis. It is conceivable that activated B-1 cells may survive in the GC due to impaired apoptosis and thus produce abnormal antibodies. These findings suggest that the immune responses of B-1 cells in the tonsillar GC could thus have an impact on the pathogenesis of IgAN. PMID- 11207663 TI - Role of macrophage migration inhibitory factor (MIF) in murine antigen-induced arthritis: interaction with glucocorticoids. AB - (MIF) is a broad-spectrum proinflammatory cytokine implicated in human rheumatoid arthritis. The synthesis of MIF by synovial cells is stimulated by glucocorticoids, and previous studies suggest that MIF antagonizes the anti inflammatory effects of glucocorticoids. This has not been established in a model of arthritis. We wished to test the hypothesis that MIF can act to reverse the anti-inflammatory effects of glucocorticoids in murine antigen-induced arthritis (AIA). Cutaneous DTH reactions and AIA were induced by intradermal injection and intra-articular injection, respectively, of methylated bovine serum albumin in presensitized mice. Animals were treated with anti-MIF MoAbs, recombinant MIF, and/or dexamethasone (DEX). Skin thickness of DTH reactions was measured with callipers and arthritis severity was measured by blinded quantitative histological assessment of synovial cellularity. Cutaneous DTH to the disease initiating antigen was significantly inhibited by anti-MIF MoAb treatment (P < 0.001). AIA was also significantly inhibited by anti-MIF MoAb (P < 0.02). DEX treatment induced a dose-dependent inhibition of AIA, which was significant at 0.2 mg/kg (P < 0.05). MIF treatment reversed the effect of therapeutic DEX on AIA (P < 0.001). DEX also significantly inhibited DTH reactions (P < 0.05) but rMIF had no effect on this effect of DEX. DTH and AIA are MIF-dependent models of inflammation and arthritis. The reversal of glucocorticoid suppression of AIA by MIF supports the concept that MIF is a counter-regulator of glucocorticoid control of synovial inflammation. Although DTH was observed to be MIF-dependent and glucocorticoid-sensitive, rMIF had no reversing effect on the suppression of DTH by glucocorticoids. This suggests that inflammatory processes in specific tissues may respond differently to MIF in the presence of glucocorticoids. PMID- 11207664 TI - CD4+ and CD8+ clonal T cell expansions indicate a role of antigens in ankylosing spondylitis; a study in HLA-B27+ monozygotic twins. AB - Ankylosing spondylitis (AS) is a complex genetic disease in which both MHC and non-MHC genes determine disease susceptibility. To determine whether the T cell repertoires of individuals with AS show signs of increased stimulation by exogenous antigens, CD4+ and CD8+ T cell subsets of five monozygotic HLA-B27+ twins (two concordant and three discordant for AS) and CD8+ T cell repertoires of three healthy HLA-B27+ individuals were characterized by TCR beta-chain (TCRB) CDR3 size spectratyping. Selected TCRB-CDR3 spectra were further analysed by BJ segment analysis and TCRB-CDR3 from expanded T cell clones were sequenced. In an analysis of all data (519/598 possible TCRB-CDR3 spectra), AS was associated with increased T cell oligoclonality in both CD8+ (P = 0.0001) and CD4+ (P = 0.033) T cell subsets. This was also evident when data were compared between individual twins. Nucleotide sequence analysis of expanded CD8+ or CD4+ T cell clones did not show selection for particular TCRB-CDR3 amino acid sequence motifs but displayed sequence homologies with published sequences from intra-epithelial lymphocytes or synovial T cells from rheumatoid arthritis patients. Together, these results provide support for the hypothesis that responses to T cell stimulating exogenous or endogenous antigens are involved in the induction and/or maintenance of AS. PMID- 11207665 TI - Up-regulation of prostaglandin E receptor EP2 and EP4 subtypes in rat synovial tissues with adjuvant arthritis. AB - To evaluate the role of the prostaglandin E receptor (EP) subtypes in the development of inflammatory synovitis, we examined EP subtype mRNA distribution in the synovial tissue of rats with adjuvant arthritis and the effect of selective EP agonists on cytokine production by cultured rat synovial cells. We used reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization to measure the level of EP subtype (EP1, EP2, EP3, and EP4) mRNA expression in synovial tissues and cultured synovial cells from the arthritic joints of rats. RT-PCR and ELISA were used to analyse the effects of two selective EP agonists on IL-6 production by cultured rat synovial cells. EP2 and EP4 mRNA expression in inflamed synovial tissues was up-regulated. EP2 and EP4 mRNA were co-expressed in synovial macrophages and fibroblasts in inflamed tissues. EP4 and EP2 agonists both inhibited IL-1-induced IL-6 production. Our results suggest that prostaglandin E2 regulates the functions of synovial macrophages and fibroblasts through EP2 and EP4, which are induced by inflammatory stimuli in rats with adjuvant arthritis. PMID- 11207666 TI - Induction of lymphocyte apoptosis in rat liver allograft with ongoing rejection by FTY720. AB - The action mechanism of FTY720, a novel immunosuppressant, is completely different from conventional immunosuppressants. The drug, which triggers apoptosis in murine and human lymphocytes, has a potent immunosuppressive activity to prevent allograft rejection without any severe side-effect. The present study was designed to determine whether FTY720 induces apoptotic cell death in activated lymphocytes infiltrated into liver grafts with ongoing rejection. FTY720 was orally administered at 5 mg/kg to the recipients on day 3 and day 4 after grafting, when the graft rejection was histologically confirmed. The intragraft patterns of IL-2, interferon-gamma (IFN-gamma), perforin, and granzyme B gene expression were detected by reverse transcriptase-polymerase chain reaction. The treatment reversed ongoing rejection and significantly prolonged recipient survival time compared with the control group. Light microscopic observation of the graft sections stained with the DNA nick-end labelling method showed that the apoptosis in the control allografts was mainly induced in hepatocytes, while that in the FTY720-treated allografts was in infiltrated lymphocytes. The rejection therapy with FTY720 did not alter the expression of IL-2, IFN-gamma, and perforin mRNAs, but slightly decreased granzyme B expression. Our results suggest that FTY720 does not alter the intrinsic lymphocyte function to produce the rejection-related cytokines, but strongly induces apoptotic cell death in the activated lymphocytes. Thus, FTY720 affords new insight into the mechanisms underlying improvements in immunosuppressive treatments. PMID- 11207667 TI - Paired cloning of the T cell receptor alpha and beta genes from a single T cell without the establishment of a T cell clone. AB - T cell receptors, which recognize antigen peptides on MHC molecules, are essential probes for the analysis of T cell antigen specificity. The identification of paired T cell receptor (TCR) chains, alpha/beta or gamma/delta, usually requires the establishment of T cell clones, which is not always available. In this study, we tried, as an alternative method, the paired cloning of TCR alpha/beta genes directly from a single T cell. T cells were sorted as a single cell from which RNA was extracted. Then, TCR alpha/beta CDR3 regions were amplified from the single cell-derived cDNA by reverse transcriptase-polymerase chain reaction to determine their sequences. We successfully identified pairs of TCR alpha/beta genes, and reconstructed the TCR molecule by a bacterial expression system. This strategy makes it possible to obtain recombinant TCR molecules from a single T cell without cellular cloning and promotes the investigation of T cell antigen specificity. PMID- 11207668 TI - Acute opioid receptor desensitization and tolerance: is there a link? AB - 1. Morphine, used long-term for the treatment of pain, results in drug tolerance. The therapeutic benefits, as well as side effects, of morphine are mediated predominantly via activation of mu-opioid receptors. Although the underlying mechanisms for opioid tolerance remains unclear, early adaptive processes, such as acute receptor desensitization and receptor downregulation, have been suggested to be crucial to the development of opioid tolerance. 2. Other neuroadaptations resulting from chronic opioid use include upregulation of the cAMP pathway, an increase in the cAMP response element-binding protein and Fos related antigens. However, the connection between upregulation of these cellular elements and the mechanism behind the behavioural phenomenon remains unclear. 3. Acute receptor desensitization is thought to occur via uncoupling of the receptor and G-protein, which is followed by internalization of the receptor from the cell membrane. This process occurs after a few minutes of agonist exposure. Receptor-G protein uncoupling is mediated via phosphorylation of putative sites on the intracellular loops of activated receptors. 4. Acute desensitization and downregulation of receptors both result in a reduction of agonist efficacy. These events occur early in the cascade of cellular adaptation; however, it is uncertain whether these processes contribute to the long-term changes in receptor sensitivity that occur after repeated exposure to opioids. 5. Acute desensitization may, in fact, be a protective mechanism whereby cells adapt to avoid the development of physiological drug tolerance by rapidly attenuating receptor-mediated signalling. Those drugs that do not cause receptor internalization, such as morphine, may have higher propensities to develop tolerance. PMID- 11207669 TI - Role of nitric oxide on pressor mechanisms within the dorsomedial and rostral ventrolateral medulla in anaesthetized cats. AB - 1. The role of nitric oxide (NO) in central cardiovascular regulation and the correlation between NO and glutamate-induced mechanisms is not clear. Microinjection of glutamate (3 nmol/30 nL) into dorsomedial medulla (DM) and rostral ventrolateral medulla (RVLM) increased arterial blood pressure (BP) and sympathetic vertebral nerve activity (VNA). Thus, in the present study, we examined the modulation by NO of glutamate-induced pressor responses in the DM and RVLM of cats. 2. Histochemical methods using nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) as a marker to stain neurons containing NO synthase (NOS), showed positive findings of NOS in both the DM and RVLM. 3. Microinjection of N(G)-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, into the DM or RVLM did not alter resting BP and VNA, but it did cause a dose-dependent attenuation of glutamate-induced pressor responses. Interestingly, the increase in NO levels that resulted from pretreatment with L arginine (L-Arg) or sodium nitroprusside (SNP) did not alter resting BP and VNA, but still inhibited glutamate-induced pressor responses in the DM and RVLM in a dose-dependent manner. 4. We also examined whether NO modulated the pressor responses induced by activation of different excitatory amino acid receptors. N Methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) were used. Consistent with the results from the initial glutamate studies, we observed that not only L-NAME, but also L-Arg and SNP attenuated pressor responses induced by NMDA and AMPA. No difference was found between the effects of NO on NMDA- and AMPA-induced pressor responses. 5. To investigate the possibility of a loss of agonist selectivity, the effects of D-2 amino-5-phosphonovalerate (D-AP5) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) on AMPA and NMDA responses in the DM were examined. The results showed that CNQX did not alter NMDA-induced pressor responses, while D-AP5 failed to alter AMPA induced responses. 6. Our results suggest that activation of the glutamate induced pressor mechanism is regulated by changes in NO levels in the DM and RVLM. This implies that NO may play a permissive role to allow operation of the glutamate-activation mechanism. PMID- 11207670 TI - Increase in gastric intramucosal hydrogen ion concentration following endotoxin challenge in the rat and the actions of nitric oxide synthase inhibitors. AB - 1. Cardiovascular events and outcome in septic shock may be predicted by monitoring the fall in intramural pH (pHi), as an index of splanchnic perfusion and mucosal ischaemia. In the present study, a small animal model for monitoring the changes of gastric pHi or intramucosal [H+] following challenge with the endotoxin lipopolysaccharide (LPS) was developed in the rat. The role of nitric oxide (NO) in these events in this model was evaluated using the non-selective NO synthase (NOS) inhibitors N(G)-nitro-L-arginine methyl ester (L-NAME) and N(G) monomethyl-L-arginine (L-NMMA). 2. The pHi and intramucosal [H+] were evaluated in omeprazole-pretreated rats (30 mg/kg, i.p.) using the Henderson equation after estimating the PCO2 and the bicarbonate concentration in gastric wall. To measure gastric wall PCO2, the oesophagus was intubated and the pylorus ligated. The PCO2 was measured by a blood gas analyser in 2 mL saline instilled for 30 min in the gastric lumen to equilibrate with the gastric wall. The pHi was measured under basal conditions and 3 and 5 h after LPS (3 mg/kg) administration. Separate groups received treatment with L-NMMA (25-50 mg/kg) or L-NAME concomitantly or 2.5 h after administration of LPS. 3. Intravenous administration of Escherichia coli LPS provoked a significant fall in gastric pHi from 7.37 to 7.18 (median values; n =10-19) determined after 5 h. In groups treated concurrently with LPS and L-NAME (5 mg/kg; n = 19), there was a similar increase in intramucosal [H+] as that induced by LPS alone (n = 15) in those animals that survived. In contrast, L-NAME (5 mg/kg; n = 12), given 2.5 h after LPS challenge, at a time at which inducible NOS is known to be significantly expressed, prevented the increase in intramucosal [H+] at 3 and 5 h after LPS challenge. Similarly, L-NMMA (25-50 mg/kg; n = 23), given 2.5 h after LPS challenge, dose-dependently inhibited the increase in intramucosal [H+] at 3 and 5 h. 4. In conclusion, these findings indicate that this rat model could be useful in exploring the pathophysiology of acute endotoxin shock. Delayed administration of L-NAME and L NMMA abolished the increase in gastric intramucosal [H+], supporting the involvement of excess NO in the tissue dysfunction associated with endotoxin shock. This suggests the potential value of this small animal model in evaluating the therapeutic activity of novel agents for use in septic shock. PMID- 11207671 TI - Suppressive effects of oxcarbazepine on tooth pulp-evoked potentials recorded at the trigeminal spinal tract nucleus in cats. AB - 1. The purpose of the present study was to evaluate the antinociceptive effect of oxcarbazepine, a keto derivitive of carbamazepine (an anticonvulsant), in an animal model. To evoke a nociceptive response, we electrically stimulated the maxillary canine tooth pulp (MCTP) in anaesthetized (allobarbital-urethane), spontaneously breathing cats. 2. The evoked potentials were recorded from the superficial layers of the caudal part of the trigeminal spinal tract nucleus (5ST). We examined a slow component with a large amplitude (the P3 component) in evoked compound potentials; its mean conduction velocity was 1.7 m/s, suggesting a response mediated by C-fibres. 3. To confirm that the P3 component was related to pain sensation, we used morphine, a most efficacious antinociceptive agent, in the present study. The P3 component was significantly suppressed by intravenous administration of morphine (3 mg/kg) and was also suppressed by microinjection of morphine (2 microg) into the recording site of the 5ST. These results suggest that the P3 component is involved in the transmission of nociceptive information. 4. We compared the effect of oxcarbazepine with mexiletine; both are known to block neuronal Na+ channels. Intravenous administration of mexiletine suppressed the P3 component at a dose of 5 mg/kg. Microinjection of mexiletine (10 microg) into the recording site of the 5ST tended to suppress the P3 component, but this effect was not significant. 5. Intravenous administration of oxcarbazepine (1-10 mg/kg) caused a dose-dependent inhibition of the P3 component, which was significantly suppressed at 10 mg/kg oxcarbazepine. Intravenous administration of 10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (MHD), a metabolite of oxcarbazepine, at doses of 3-30 mg/kg caused a dose-dependent inhibition of the P3 component. Oxcarbazepine was not available for the microinjection study because it is not water soluble. We used MHD for the microinjection study instead of oxcarbazepine, because MHD can be dissolved in water up to 3 mg/mL. Microinjections of MHD (6 microg) into the recording site of the 5ST suppressed the P3 component. These results indicate that oxcarbazepine has an antinociceptive action. PMID- 11207672 TI - Effects of ageing on the activation metabolism of rat papillary muscles. AB - 1. A myothermic technique has been used to investigate the mechanics and energetics of left ventricular papillary muscles from 6-, 15-, 22- and 27-32 month-old Sprague-Dawley rats. 2. There was a significant increase in the left ventricular mass to body mass (LVM:BM) ratio in the senescent. 27-32-month-old group of animals compared with the younger animals (P<0.05). 3. The maximum stress developed in the senescent groups was reduced by almost 40% in comparison with the stress developed by the 6-, 15- and 22-month-old groups (P<0.001). The mean rise time, half relaxation time and half width were increased significantly (P<0.05) in the 22-month-old group but, unexpectedly, this effect was not seen in the senescent group. 4. Heat production per beat versus total stress relationships were obtained in two different ways to determine the magnitude of the activation heat and the isometric economy (given by the slope of the relationship). The activation heat was not significantly different between groups with either method, but there was a significant increase (P<0.001) in the economy with which stress was developed in the senescent group in comparison with the 6- and 15-month-old groups. 5. A combination of forskolin (2.5-6.5 micromol/L) and high Ca2+ (7.5 mmol/L) was used to increase the energy usage per beat. In the 6- and 15-month-old groups, these agents caused a four-fold increase in the activation heat magnitude compared with a less than two-fold increase in the 22 month-old and senescent groups (P<0.001). There was no effect of forskolin/high calcium on the slope of the heat:total stress relationship. 6. The data suggest that, under conditions known to increase cardiac contractility, there is a reduced ability to cycle calcium in the 22-month-old and senescent groups relative to the young adult 6-month-old and adult 15-month-old groups. PMID- 11207673 TI - Contractile and electrical properties of sternohyoid muscle in streptozotocin diabetic rats. AB - 1. The effects of diabetes on the electrical and contractile function of skeletal muscle are variable, depending on muscle fibre type distribution. The muscles of the upper airway have a characteristic fibre distribution that differs from previously studied muscles, but the effects of diabetes on upper airway muscle function are unknown. Normally, contraction of upper airway muscles, such as the sternohyoids, dilates and/or stabilizes the upper airway, thereby preventing its collapse. Diabetes is associated with obstructive sleep apnoea in which there is collapse of the upper airway due to failure of the upper airway musculature to maintain airway patency. Therefore, the purpose of the present study was to determine the effects of diabetes on the electrical and contractile characteristics of upper airway muscle. 2. Rats were treated with vehicle (sodium citrate buffer; pH 4.5) or with streptozotocin to induce diabetes, confirmed by the presence of hyperglycaemia, and the contractile and electrical properties of the sternohyoid were compared in these two groups. Isometric contractile properties and membrane potentials were determined in isolated sternohyoid muscles in physiological saline solution at 25 degrees C. 3. Streptozotocin had no effect on sternohyoid muscle fatigue, the tension-frequency relationship or membrane potentials, but did increase contraction time, half-relaxation time, twitch tension and tetanic tension. 4. Streptozotocin-induced diabetes has no effect on sternohyoid muscle fatigue or the tension-frequency relationship, but does reduce contractile kinetics and increases force generation. These effects are not due to changes in resting membrane potential. These data are evidence that the association of sleep apnoea and diabetes is not due to effects on upper airway muscle contractile properties. PMID- 11207674 TI - Association of serum tumour necrosis factor-alpha with serum low-density lipoprotein-cholesterol and blood pressure in apparently healthy Japanese women. AB - 1. The pro-inflammatory cytokine tumour necrosis factor (TNF)-alpha is considered to be involved in the development of atherosclerosis by inducing local inflammatory responses in the vascular wall. Because TNF-alpha is also known to affect lipid and glucose metabolism, the association between the circulating concentration of TNF-alpha and atherogenic risk factors was examined in 82 apparently healthy Japanese women (aged 19-69 years; mean age 48.5 years). 2. The mean (+/-SD) serum TNF-alpha concentration was 2.7+/-0.9 pg/mL (range 1.4-5.9 pg/mL). The TNF-alpha concentration showed significant correlations with age (r = 0.28; P = 0.01), body mass index (r = 0.27; P = 0.01), the waist-hip ratio (r = 0.41; P = 0.0002), percentage body fat (r = 0.30; P = 0.006), systolic (r = 0.32; P = 0.004) and diastolic (r = 0.24; P = 0.03) blood pressure, total cholesterol (r = 0.27; P = 0.02) and low-density lipoprotein-cholesterol (LDL-C; r = 0.36; P = 0.001), while the correlations with high-density lipoprotein-cholesterol (r = 0.20; P = 0.08) and insulin resistance estimated by the homeostasis model assessment (HOMA(IR); r = 0.16; P = 0.15) were not statistically significant. 3. When adjusted for age and menopause, TNF-alpha was significantly associated with systolic blood pressure (r = 0.25; P = 0.02) and LDL-C (r = 0.27; P = 0.02). The association between TNF-alpha and LDL-C remained significant when adjustment was made for age, menopause and the waist-hip ratio (r = 0.24; P = 0.03). 4. Our results indicate that TNF-alpha may play a role in modulating blood pressure and LDL-C. PMID- 11207675 TI - Role of protein kinase C, K(ATP) channels and DNA fragmentation in the infarct size-reducing effects of the free radical scavenger T-0970. AB - 1. In the present study, we investigated the effect of 1-(3-tert-butyl-2-hydroxy 5-methoxyphenyl)-3-(3-pyridylmethyl) urea hydrocloride (T-0970), a novel water soluble low-molecular weight free radical scavenger, on the generation of hydroxyl radicals in vivo and on myocardial infarct size in an in vivo model of myocardial infarction in rabbits. 2. T-0970 scavenged hydroxyl radicals generated in the myocardium during reperfusion, as assessed by using a microdialysis technique and HPLC in an in vivo model with 30 min coronary occlusion and 30 min reperfusion in rabbits. 3. Another group of rabbits was subjected to 30 min coronary occlusion and 48 h reperfusion. The control group (n = 10) was infused with saline for 190 min from 10 min before occlusion to 180 min after reperfusion. The treatment group (T-0970 group; n = 10) was injected with a bolus 2.5 mg/kg T-0970 and then infused with T-0970 for 190 min from 10 min before reperfusion to 180 min after reperfusion at a rate of 100 microg/kg per min. The T-0970 + CHE group (n = 5) was given chelerythrine (CHE; a selective inhibitor of protein kinase C (PKC); 5 mg/kg, i.v.) 10 min before the administration of T 0970. The T-0970 + 5-HD group (n = 5) was given 5-hydroxydecanoate (5-HD; an inhibitor of mitochondrial K(ATP) channels; 5 mg/kg, i.v.) 10 min before the administration of T-0970. The CHE and 5-HD groups were given CHE (5 mg/kg, i.v.) and 5-HD (5 mg/kg, i.v.) 20 min before reperfusion, respectively. After 48 h reperfusion, infarct size was measured histologically and expressed as a percentage of the area at risk (AAR). In another series of experiments, the control (n = 5) and T-0970 (n = 5) groups were killed 4 h after reperfusion following 30 min coronary occlusion and DNA fragmentation in myocytes was assessed using in situ dUTP nick end-labelling (TUNEL) at the light microscopic level. 4. Infarct size, as a percentage of AAR, in the T-0970 group was significantly reduced compared with the control group (21+/-4 vs 41+/-4%, respectively; P<0.05). This reduction of infarct size by T-0970 was abolished by pretreatment with CHE and 5-HD. Neither CHE nor 5-HD alone had any effect on infarct size. The percentage of infarcted myocytes with DNA fragmentation by TUNEL in the T-0970 group was significantly reduced compared with the number in the control group (4.0+/-1.5 vs 10.7+/-1.9%, respectively; P<0.05). 5. T-0970, a free radical scavenger, improved reperfusion injury. This effect seemed to be mediated by activation of PKC, the opening of mitochondrial K(ATP) channels and inhibition of DNA fragmentation. PMID- 11207676 TI - Subarachnoid haemorrhage-induced sympathoexcitation in rats is reversed by bosentan or sodium nitroprusside. AB - 1. The roles played by nitric oxide (NO) and endothelin (ET) in the genesis of sympathetic nervous activation following experimental subarachnoid haemorrhage was investigated using spectral analysis of blood pressure rhythms. 2. Subarachnoid haemorrhage was induced in conscious rats by injecting 0.3 mL homologous blood via a catheter placed along the surface of the brain and directed towards the circle of Willis. Three hours after the insult and after sympathetic activation was evident, animals received either an acute injection of the ET antagonist bosentan (5 mg/kg, i.v.; n = 7), an infusion of the NO donor sodium nitroprusside (SNP; 18 microg/h; n = 7) or no treatment (n = 7). 3. Three hours following the induction of subarachnoid haemorrhage, the mid-frequency components of systolic blood pressure were markedly elevated, indicating a pronounced sympathoexcitation. However, blood pressure and heart rate levels remained unchanged at this time. In the absence of treatment, the mid-frequency components of blood pressure remained elevated for a subsequent 2 h. Treatment with a non-hypotensive dose of SNP reversed the sympathoexcitation within 1 h. Treatment with bosentan was also effective in reducing the mid-frequency oscillations in blood pressure associated with subarachnoid haemorrhage. 4. Our results indicate that subarachnoid haemorrhage is associated with an acute activation of the sympathetic nervous system. The degree of sympathoexcitation can be reversed by the use of either bosentan or SNP. PMID- 11207677 TI - KRH-594, a new angiotensin AT1 receptor antagonist, prevents end-organ damage in stroke-prone spontaneously hypertensive/Izm rats. AB - 1. In the present study, we examined whether KRH-594, a new angiotensin AT1 receptor antagonist, would stop the progression of renal failure and end-organ damage and improve the survival rate in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP/Izm). 2. Oral administration of KRH-594 (3 and 10 mg/kg per day) for 11 weeks significantly reduced systolic blood pressure, urinary total protein, blood urea nitrogen, serum creatinine and urinary N-acetyl glucosaminidase and increased creatinine clearance in SHRSP/Izm. 3. In a histological study, KRH-594 (3 and 10 mg/kg per day) significantly improved the glomerulosclerosis, basophilic change and hyalin cast of tubules, proliferation of afferent arterioles and interlobular artery wall scores of the kidney and the cardiac fibrosis scores of the heart in SHRSP/Izm. KRH-594 (3 and 10 mg/kg per day) also significantly inhibited cardiac hypertrophy. 4. KRH-594 (3 and 10 mg/kg per day) prevented death in SHRSP/Izm during the examination period. 5. These results suggest that KRH-594 improves hypertensive complications, such as renal failure, cardiac hypertrophy and thickening of the artery wall, and prevents death in salt-loaded SHRSP/Izm. PMID- 11207678 TI - Inhibitory effect of reactive oxygen species on angiotensin I-converting enzyme (kininase II). AB - 1. Somatic angiotensin I-converting enzyme (ACE) is a protein that contains two similar domains (N- and C-terminal), each possessing an active site. We have examined the effects of a generator of hydroxyl radicals (g*OH: 2,2'-azo-bis(2 amidinopropane)) and hydrogen peroxide (H2O2) on ACE using an in vitro approach. 2. The generator of hydroxyl radicals inactivated ACE in a time (2-6 h)- and concentration (0.3-3 mmol/L)-dependent manner at 37 degrees C. When ACE was coincubated for 4 h with g*OH (3 mmol/L), its activity decreased by 70%. Addition of dimethylthiourea or mannitol + methionine, two *OH scavengers, resulted in a significant protection of ACE activity. Mercaptoethanol and dithiotreitol, two thiol-reducing agents, also efficiently protected ACE activity. 3. The hydrolysis of two natural and domain-specific substrates was explored. The hydrolysis of angiotensin I, preferentially cleaved by the C-domain, was significantly inhibited (57-58%) after 4 h exposure to g*OH (0.3-1 mmol/L). Under the same conditions of exposure, the hydrolysis of N-acetyl-Ser-Asp-Lys-Pro, a specific substrate for the N-domain, was only slightly inhibited by 1 mmol/L g*OH. 4. Hydrogen peroxide, another source of *OH, was used. After exposure to H2O2 (3 mmol/L; 4 h), an 89% decrease in ACE activity was observed. Pretreatment with the iron chelator deferoxamine (1 mmol/L) attenuated H2O2-mediated ACE inactivation, demonstrating that the effect of H2O2 was partly due to its conversion into *OH (Fenton reaction). 5. In summary, our findings demonstrate that g*OH and H2O2 inhibit ACE activity and suggest a preferential action of g*OH on the C-domain of the enzyme. PMID- 11207679 TI - Effective treatment of leg vein telangiectasia with a new 940 nm diode laser. AB - BACKGROUND: A variety of lasers have been used in an attempt to treat leg vein telangiectasia OBJECTIVE: To evaluate the feasibility of a new 940 nm diode laser for the treatment of leg vein telangiectasia. METHODS: Thirty-one patients with leg vein telangiectasia were treated with a diode laser; 26 of these with 940 nm, 300-350 J/cm2, 40-70 msec, 1.0 mm handpiece, one pass, and 5 of these with 940 nm, 815 J/cm2, 50 msec, 0.5 mm handpiece, one pass. Each subject had three treatments of the same site at 4-week intervals. Photographs taken before and 4 weeks after the last treatment were evaluated by two independent observers for vessel clearance. RESULTS: In those 26 patients treated with a fluence of 300-350 J/cm2, a vessel clearance of greater than 50% was achieved in 20 patients (76%), 12 of these patients had clearance rates greater than 75%. A clearance rate of less than 50% was obtained in six patients, with three of these patients showing responses of less than 25%. In five patients treated with a fluence of 815 J/cm2 a clearance rate of more than 75% was observed. CONCLUSIONS: In this preliminary study a 940 nm diode laser was shown to be safe and effective for the treatment of leg vein telangiectasia. PMID- 11207680 TI - Resurfacing of pitted facial acne scars with a long-pulsed Er:YAG laser. AB - BACKGROUND: Conventional short-pulsed Er:YAG lasers show less effective hemostasis and weak photothermal damage on papillary dermis. Recently, newer long pulsed Er:YAG laser systems has been developed. OBJECTIVE: To evaluate the clinical and histologic effects of long-pulsed Er:YAG laser resurfacing for pitted facial acne scars. METHODS: Thirty-five patients with pitted facial acne scars were treated with a long-pulsed Er:YAG laser. All patients had Fitzpatrick skin phototypes III-V. A pulsed Er:YAG laser with a 5 mm handpiece at a setting of 7.0-7.5 J/cm2 with a 10-msec pulse duration was used. The laser was fired at 5 Hz, with four to five passes. In 28 patients, the results of laser treatment were evaluated for the degree of clinical improvement, duration of erythema, pigmentary change, and any adverse events at 2 weeks, 1 month, and 3 months. In seven patients, skin biopsy specimens were obtained at the following intervals: immediately, 1 week, 2 weeks, 4 weeks, and 8 weeks postoperatively for histologic examination. RESULTS: The results of long-pulsed Er:YAG laser resurfacing for pitted facial acne scars were excellent in 10 patients (36%), good in 16 patients (57%), and fair in 2 patients (7%). Erythema occurred in all patients after laser treatment and lasted longer than 3 months in 15 patients (54%). Postinflammatory hyperpigmentation occurred in 8 patients (29%). But the pigmentation faded or disappeared within 3 months. One patient (4%) experienced mild hypopigmentation. Pruritic symptoms that required medical intervention occurred in 16 patients (57%). Mild to moderate postoperative acne flare-up occurred in 8 patients (29%). No other adverse effects such as scarring, bacterial infection, or contact dermatitis were observed. CONCLUSION: In conclusion, resurfacing with a long pulsed Er:YAG laser is a safe and very effective treatment modality for pitted facial acne scars. PMID- 11207681 TI - Facial rejuvenation with a nonablative 1320 nm Nd:YAG laser: a preliminary clinical and histologic evaluation. AB - BACKGROUND: Rejuvenation of photoaged skin involves removal of the epidermis and superficial dermis, encouraging the production of new epidermis with collagenesis and remodeling. The facial appearance during healing is unpleasant, and the complication rate is high. OBJECTIVE: We evaluate a Q-switched Nd:YAG laser operating at 1320 nm, with a cryogen delivery system and a skin temperature sensor. The system cools the target skin, followed by the laser impulse which passes through the cooled epidermis into the dermis. METHODS: Ten patients are presented. Two treatments a week were given over 4 weeks, and the patients were seen at 2 and 6 weeks after the final treatment. RESULTS: The histology showed improvement in the condition of the dermis in all 10 patients, but only 2 of the 10 patients expressed satisfaction with the results, despite similar histologic findings. CONCLUSIONS: Careful patient selection is required. Better patient education is necessary to ensure that the patients' expectations are realistic. We should add treatments that will improve the youthful aspect of the epidermis. The system may well help in maintaining the effects of collagen remodeling following traditional ablative resurfacing procedures, but studies are necessary to show this. PMID- 11207682 TI - Endovenous laser: a new minimally invasive method of treatment for varicose veins -preliminary observations using an 810 nm diode laser. AB - BACKGROUND: Long-term success in the treatment of truncal and significant branch leg varicosities, when the saphenofemoral junction (SFJ) and the greater saphenous vein (GSV) are involved, depends on the elimination of the highest point of reflux and the incompetent venous segment, and is best achieved by surgical ligation and stripping. Minimally invasive alternatives in the treatment of varicose veins with SFJ and GSV incompetence have been tried over the years to increase patient comfort, reduce cost and risk, and allow implementation by a wide variety of practitioners resulting in varying degrees of success depending on the fulfillment of the above two premises and the effectiveness of the method used. OBJECTIVE: To demonstrate a novel way to use laser energy through an endoluminal laser fiber for the minimally invasive treatment of truncal varicosities that eliminates the highest point of reflux and the incompetent segment. METHODS: Patients were treated with 810 nm diode laser energy administered endovenously through a bare-tipped laser fiber (400-750 microm). Vein access for endoluminal placement of the fiber through a catheter was achieved by means of percutaneous or stab wound incision under ultrasound guidance and local anesthesia. Exact placement of the fiber was determined by direct observation of the aiming beam through the skin and by ultrasound confirmation. RESULTS: Preliminary short-term postprocedure results (up to 1 year, 2 months after treatment) in the endovenous laser treatment of 40 greater saphenous veins in 33 patients indicate a 100% rate of closure with no significant complications. In addition, a 2-year experience of 80 cases of isolated branch varicosities (Giacomini, anterolateral branch, etc.) also shows a 100% rate of closure. CONCLUSION: Early results of our endoluminal laser methodology indicate a very effective and safe way to eliminate SFJ incompetence and close the GSV. With proper patient selection, the ease of methodology and the reduced risk and cost associated with endovenous laser treatment may make it a successful minimally invasive alternative for a wide group of patients that previously would have required ligation and stripping. PMID- 11207683 TI - Micropigmentation as an adjuvant in cosmetic surgery of the scalp. AB - BACKGROUND: Unsightly scalp scars, refractory to surgical revision, can pose a difficult therapeutic problem. Application of cosmetics for camouflage is time consuming, repetitive, expensive, and seldom satisfactory. Treatment of scalp scars with micropigmentation has never been reported. OBJECTIVE: To show that iron oxide micropigmentation of scalp scars is simple, safe, and effective. METHODS: A commercially available micropigmentation system, sterile needle assemblies, and appropriately colored iron oxide pigments were used in all procedures. Due to the varying textures of scalp scars, greater force was required in some areas to achieve proper needle penetration. Once the scar area was pigmented, the surrounding scalp was also pigmented to obtain a "feathering" effect. RESULTS: The cosmetic improvement after micropigmentation was always dramatic and all patients were pleased with the results. About 22% of the patients requested a touch-up of the micropigmentation to reinforce the residual pigment. Frontal edema was the only complication and was seen in one patient. CONCLUSION: Micropigmentation of the scalp is a safe and effective technique for camouflaging scalp scars. PMID- 11207684 TI - Presurgical ultrasound-guided anchor-wire marking of soft tissue metastases in stage III melanoma patients. AB - BACKGROUND: Due to increased sensitivity of diagnostic procedures, soft tissue metastases in melanoma patients are frequently detected very early. However, small sizes, deep location, or position close to vulnerable structures could render subsequent surgery quite difficult. OBJECTIVE: To test the feasibility and effectiveness of presurgical ultrasound-guided anchor-wire marking of melanoma metastases. METHODS: We selected melanoma patients with cytologically proven metastases in clinical stage III which were either unfavorably located or which have failed removal by previous surgery. Anchor-wire marking was performed ultrasound guided and free-hand style without the use of local anesthesia. RESULTS: Twelve procedures in nine patients were well tolerated without any complications. In 11 cases the wire tip proved to be located within the tumor lesion; in one case the wire tip missed the target by less than 5 mm and thus was close enough to support appropriate surgery. Earlier, 3 of the 12 study lesions had undergone unsuccessful surgery. The median diameter of the removed metastases was 18.5 mm (range 7-30 mm). CONCLUSION: Ultrasound-guided anchor-wire marking of unfavorably located melanoma metastases is feasible and might facilitate subsequent surgery. PMID- 11207685 TI - Reasons for ulceration after injection treatment of telangiectasia. AB - BACKGROUND: Sclerotherapy of telangiectasias is widely used for their treatment, but causes skin ulceration in 0.2-1.2% of patients. The cause of this complication is still unclear. OBJECTIVE: We hypothesized that an arteriole is occluded because the sclerosant gets into an arteriovenous (AV) shunt. We have looked for these communications underneath the telangiectasias. METHODS: Doppler examination was performed in 155 cases above the telangiectasias to reveal the presence of an AV shunt. Twenty-two positive sites were excised and histologically screened for AV shunts. RESULTS: Pulsatile sound could be detected by Doppler transducer above spider veins in 112 cases (72.2%). Of the 22 Doppler positive telangiectasias, 19 AV microshunts could be found histologically. CONCLUSIONS: Understanding the mechanism of this complication can lead to its prevention. No more than 0.2 ml of sclerosant should be administered to a single site. The warning sign of backwash of sclerosant into arterials is the temporary blanching of the skin from the arterial spasm. PMID- 11207686 TI - Topical L-ascorbic acid: percutaneous absorption studies. AB - BACKGROUND: Reactive oxygen species generated by ultraviolet light result in photocarcinogenic and photoaging changes in the skin. Antioxidants protect skin from these insults. OBJECTIVE: This study defines formulation characteristics for delivering L-ascorbic acid into the skin to supplement the skin's natural antioxidant reservoir. METHODS: L-ascorbic acid or its derivatives were applied to pig skin. Skin levels of L-ascorbic acid were measured to determine percutaneous delivery. RESULTS: L-ascorbic acid must be formulated at pH levels less than 3.5 to enter the skin. Maximal concentration for optimal percutaneous absorption was 20%. Tissue levels were saturated after three daily applications; the half-life of tissue disappearance was about 4 days. Derivatives of ascorbic acid including magnesium ascorbyl phosphate, ascorbyl-6-palmitate, and dehydroascorbic acid did not increase skin levels of L-ascorbic acid. CONCLUSIONS: Delivery of topical L-ascorbic acid into the skin is critically dependent on formulation characteristics. PMID- 11207687 TI - Bowen's disease (squamous cell carcinoma in situ) in immunosuppressed patients treated with imiquimod 5% cream and a cox inhibitor, sulindac: potential applications for this combination of immunotherapy. AB - BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) often have a protracted course. However, all these patients are immunosuppressed and may have a high incidence of cutaneous malignancies. OBJECTIVE: To determine if combination therapy using topical imiquimod cream 5% and the oral cyclooxygenase (COX) inhibitor are useful in the therapy of squamous cell carcinoma in situ (SCC in situ)/Bowen's disease in patients with long-standing CLL. METHODS: Five CLL patients with head and neck cutaneous SCC in situ, which met criteria for Bowen's disease, were treated with topical 5% topical imiquimod cream and an oral COX inhibitor, sulindac 200 mg twice a day. RESULTS: All patients showed clinical resolution and histologic clearing of the tumors after 16 weeks of therapy. CONCLUSION: The local immune modulator, 5% imiquimod, in combination with a COX inhibitor, with its many potential antitumor effects may stimulate the innate and possibly the adaptive immune responses to clear these malignancies. PMID- 11207688 TI - Immediate postoperative laser resurfacing improves second intention healing on the nose: 5-year experience. AB - BACKGROUND: Mohs surgery defects on convex nasal surfaces do not reliably heal well by second intention. Prior to the availability of laser resurfacing we found that immediate postoperative dermabrasion improved the predicted outcome from second intention healing for these defects. OBJECTIVE: To determine the ability of immediate postoperative CO2 and Er:YAG laser resurfacing to improve predicted healing by second intention. METHODS: Seventy-four patients with Mohs surgical defects on the nose underwent immediate postoperative resurfacing with either a scanned CO2 or long-pulsed Er:YAG laser. Thirty patients had photographs of appropriate quality and follow-up for evaluation by a panel of nine objective physicians. RESULTS: All 74 patients were satisfied with their result and none have requested scar revision. Of the 30 patients evaluated by the panel, all were scored acceptable to excellent. CONCLUSION: Immediate laser resurfacing can improve the predicted outcome from second intention healing on the nose and should be considered for select patients. PMID- 11207689 TI - Ocular damage due to chlorhexidine versus eyeshield thermal injury. AB - BACKGROUND: Ocular damage may occur from a number of mechanisms during laser use. OBJECTIVE: To review issues relevant to ocular protection during laser resurfacing. METHODS: The authors were consulted to evaluate the thermal energy transferred from the outer to the inner (ie, corneal contact) surface of stainless steel eyeshields following direct exposure to the carbon dioxide (CO2) resurfacing laser beam. Measurements were obtained using thermocouples (attached to the inner surface of the eyeshields) and analyzed with a computer-based acquisition system. RESULTS: A maximum eyeshield temperature increase of 13 degrees C above the ambient temperature was noted following one pass with a CO2 resurfacing laser (Sharplan continuous CO2 laser with Clinicon SureScan scanner, 15 W, 950 microsec pulse duration, square spot of 9 mm). CONCLUSION: The eyeshields analyzed in this study minimized thermal transfer following a single direct hit with a CO2 resurfacing laser. An understanding of the potential mechanisms of ocular injury is essential in preventing its occurrence. PMID- 11207690 TI - Minimizing postoperative drainage with 20% ferric chloride after chemical matricectomy with phenol. AB - BACKGROUND: Phenol used in partial matricectomy shows its effects by denaturing matrix proteins. This highly successful method has the major problem of oozing which can continue for 5-6 weeks. OBJECTIVE: The goal of this study was to determine the effect of 20% ferric chloride (FC) (FeCl3) on minimizing the oozing after chemical matricectomy with phenol. METHODS: Sixty-seven patients with stage III onychocryptosis were treated by chemical matricectomy with 90% aqueous phenol. In 32 of these patients FC was applied to the nail bed after the phenolization procedure. RESULTS: We found a statistically significant (P <.001) reduction of oozing in the FC-applied group of patients. CONCLUSION: We think that using FC after phenol chemical matricectomy results in a significant reduction in oozing from the operation site. PMID- 11207691 TI - The versatility of the nasolabial flap enhanced by the delay procedure. AB - BACKGROUND: The nasolabial flap is a versatile and effective option for the closure of nasal defects of the cheek and nasal sidewall following Mohs surgery. However, both extirpation of a tumor in the region of the base of the flap or previous use of the flap often destroy the proximal axial blood supply to the flap, excluding its immediate utilization. We describe a different use of the nasolabial flap and a technique for preserving its capacity in the case of reutilization OBJECTIVE: To describe the versatility of the nasolabial flap and a delay procedure that enables its exploitation despite prior disruption of the proximal blood supply. METHODS: Three different uses of the same nasolabial flap are demonstrated in one patient. The surgical techniques are discussed in detail. RESULTS: The reconstructive results were excellent. There were no postoperative complications. CONCLUSION: The nasolabial flap is a versatile and effective option for the closure of nasal defects of the cheek and nasal sidewall. When the nasolabial flap has been used before, or its blood supply compromised, the delay procedure can reestablish its applicability. PMID- 11207692 TI - Merkel cell carcinoma of the skin and mucosa: report of 12 cutaneous cases with 2 cases arising from the nasal mucosa. AB - BACKGROUND: Merkel cell carcinoma (MCC) is an uncommon skin tumor that most frequently arises on sun-exposed facial sites. It rarely occurs on mucous membranes of the head region. The primary MCC is usually treated by wide excision followed by radiation to the primary site and regional lymph nodes. Using traditional surgery the local recurrence rate ranges from 20 to 50%. In our clinic, Mohs surgery is used to excise the primary MCC completely, followed by radiation. Here we present our treatment experiences and outcomes. OBJECTIVE: To document our experience of MCC treated by Mohs surgery. We present our series of 12 cases of MCC, 2 cases of which arose from mucosal sites of the nasal cavity. METHODS: We reviewed 12 cases of MCC from the Mohs clinic database. We also reviewed the literature for cutaneous and mucosal MCC. RESULTS: There were 12 cases of MCC: 10 cutaneous and 2 mucous. The site distribution of cutaneous MCC was eight on the head, one on the neck, and one on the groin. Of these, nine were treated by Mohs excision. Two patients developed local recurrence following Mohs treatment. The local recurrence rate was 22% (2 of 9). The sites of mucosal MCC were the nasal septum and nasopharynx. One case had a history of previous radiation and developed an MCC 40 years later. This case also demonstrated epidermotropic spread of Merkel cells to the overlying mucous epithelium. This patient required extensive intranasal and cranial surgery to remove the tumor. Both patients with mucosal MCCs died of their disease. The overall mucocutaneous survival of MCC at 1 year was 80% and at 2 years was 50%. CONCLUSION: In our series, local control of the primary MCC was achieved in 70% of patients (7 of 10) using combined Mohs excision and radiation. Two recurrences had primary tumors larger than 3.5 cm in diameter, while the other case was nonresectable by Mohs surgery. Tumor size appeared to determine the degree of local control. When the postoperative Mohs defect was less than 3.0 cm in diameter, local and regional control appeared to be more favorable. When the primary facial MCC is relatively small, removal by Mohs surgery followed by radiation was effective, therapeutic, and less disfiguring. Mucosal MCC is rare and may occur as a long term sequelae after radiation therapy to the skin. PMID- 11207693 TI - Effect of the 585 nm flashlamp-pumped pulsed dye laser for the treatment of keloids. AB - BACKGROUND: Due to its potential effects on skin microcirculation and collagen metabolism, the 585 nm flashlamp-pumped pulsed dye laser has been proposed for treating abnormal scars. Indeed, one of the main problems with keloidal scars is their disfiguring erythematous color. OBJECTIVE: To assess the efficacy of the 585 nm pulsed dye laser on the appearance of keloids. METHODS: Eleven patients with skin phototypes II-IV and keloids were treated with the 585 nm pulsed dye laser. After one to three treatment sessions, clinical assessments of the scars were performed in combination with remittance spectroscopy measurements of the redness and melanin pigmentation. A group of nine keloids covered by silicone gel sheeting served as controls. Data were compared statistically. RESULTS: During laser treatments, a discrete decrease in redness of the scars was clinically reported. However, this improvement was not confirmed by the objective spectrophotometric data. No side effects, especially hyperpigmentation, were disclosed. The keloids redness was not improved in the control group. CONCLUSION: The 585 nm pulsed dye laser yields only minimal effects, if any, on the erythema of keloids. Similarly silicone gel sheeting does not modify the keloids redness. PMID- 11207694 TI - Moist wound healing with occlusive dressings: a clinical focus. AB - The concept of moist wound healing, which is facilitated by the application of occlusive dressings, dates back to 1615 BC, and the technique is currently supported by a relatively large volume of data. It is clear that occlusive dressings are in many cases associated with more rapid reepithelialization, a reduced risk of infection, and more rapid wound healing than the alternatives. Nevertheless, many clinicians have been slow to accept this therapeutic technique. This article traces the history of moist wound healing from its earliest inception, examines the theoretical mechanisms of its effect, and explores its advantages and disadvantages. It also reviews the literature supporting the use of occlusive dressings in a variety of wound settings and examines the possible reasons behind the apparent reluctance on the part of the medical community to accept a potentially valuable therapy. PMID- 11207695 TI - Forceps and cotton applicator method of freezing benign lesions. AB - BACKGROUND: Cryosurgery is one of the most common treatment methods in the dermatologists armamentarium. We describe a method combining forceps and a cotton applicator to freeze benign lesions for practitioners who prefer to use cotton tipped applicators instead of a cryosurgery spray device. METHODS: We describe the technique using common in-office instruments. CONCLUSION: Lesions around delicate areas can be treated with forceps and a cotton-tipped applicator dipped in liquid nitrogen resulting in less pain and decreased collateral damage vs. traditional methods. For the most delicate areas, the forceps dipped directly in liquid nitrogen method is preferred. PMID- 11207696 TI - Human anti-hyaluronic acid antibodies: is it possible? AB - BACKGROUND: Although hyaluronan has been acknowledged as being free of species and organ specificity, for 4 years I have encountered a variety of adverse reactions to injectable hyaluronic acid as used in aesthetic medicine. OBJECTIVE: I have tried to prove that some of those side effects may be allergic reactions to the commercial preparations of injectable hyaluronic acid. METHODS: I began with intradermal tests to the reactive patients and to 2 witnesses; then lymphocyte transforming tests were performed at the University of Geneva (Switzerland). Histology was performed on the skin tests and on reactive treated areas of the face of different patients. A serum analysis was then done by Pr. Sainte Laudy of Laboratoire Pasteur--Cerba (France). RESULTS: The skin tests were positive for one or the other or both of the injectable hyaluronic acid preparations used in aesthetic medicine. The different biopsies have shown for some a chronic inflammatory reaction, even 11 months after the treatment or a severe granulamatous reaction to foreign bodies. Serum analysis revealed positive antibodies against Restylane and/or Hylaform and even IgG and E anti-hyaluronic acid. CONCLUSION: Since 1995, I have 8 patients with adverse reactions to injectable hyaluronic acid, which after several tests, may be allergic to those products. Isn't it time to introduce intradermal tests before any injection of this type, as done with injectable bovine collagen? PMID- 11207697 TI - Renal cell carcinoma metastatic to the scalp: case report and review of the literature. AB - BACKGROUND: Renal cell carcinoma metastatic to the skin is rare. OBJECTIVE: To illustrate by a case report the clinical presentation and management of the disease. METHODS: We present a case of renal carcinoma metastatic to the skin of the scalp that occurred 6 years after removal of her kidney. The tumor was diagnosed using frozen tissue and paraffin sections. RESULTS: Cutaneous metastasis treated by excision. CONCLUSION: Renal cell carcinoma may metastasize to the skin of the scalp. Our case illustrated an interesting ipsilateral metastasis that occurred 6 years after treatment of her primary tumor. Physicians, dermatologists, pathologists, and Mohs surgeons should be aware of this entity. PMID- 11207698 TI - Basal cell carcinoma arising in a cleft lip repair scar. AB - BACKGROUND: A case of basal cell carcinoma (BCC) developing in the repair scar of a cleft lip is presented. OBJECTIVE: Primary BCCs arising in surgical scars are very rare and no known reported cases exist of a BCC developing in a surgically repaired cleft lip scar. METHODS: A 69-year-old white man presented with a 5 mm primary BCC on his upper lip at the site of his cleft lip repair scar. The diagnosis was made by a tangential biopsy that showed an ulcerated BCC. RESULTS: Review of the medical literature indicates that a scar may be an independent risk factor for developing BCC. CONCLUSION: BCC may rarely arise in a cleft lip repair scar. PMID- 11207699 TI - Adverse granulomatous reaction after cosmetic dermal silicone injection. AB - BACKGROUND: Various alloplastic injectable implants have been developed for soft tissue augmentation without surgery, but different local or systemic adverse reactions have limited their use for cosmetic purposes. OBJECTIVE: To examine the problems associated with silicone injection. METHODS: Case report and literature review. RESULTS: We describe an adverse granulomatous reaction after the injection of liquid silicone for lip augmentation, causing facial disfigurement. Although the initial response to steroids was poor, after 3 years of follow-up the nodules have almost disappeared spontaneously. CONCLUSION: We advise that silicone injection be performed solely by trained physicians using medical-grade silicone or consider other injectable materials. PMID- 11207700 TI - Rhinophyma and coexisting occult skin cancers. AB - BACKGROUND: Although coexistent tumors have been reported in patients with rhinophyma, few reports have described the coexistence of rhinophyma and an occult infiltrating squamous cell carcinoma (SCC). OBJECTIVE: Preoperatively and during rhinophymaplasty, recognition of subtle changes can suggest an underlying malignancy. METHODS: A large infiltrating SCC was noted during electrosurgical rhinophymaplasty. Mohs micrographic surgery was performed to clear the tumor. RESULTS: The patient was tumor-free with no evidence of recurrence at 1-year follow-up. CONCLUSION: In the evaluation of changing rhinophyma or subtle changes in tissue noted during rhinophymaplasty, physicians must consider the possibility of an underlying malignancy. PMID- 11207701 TI - Bilateral auricular squamous cell carcinomas with perineural invasion. AB - BACKGROUND: Bilateral squamous cell carcinoma (SCC) of the external ears is a rare phenomenon, and we are unaware of instances of bilateral perineural involvement. OBJECTIVE: To describe bilateral auricular SCCs, each with perineural invasion. METHODS: Case report and literature review. RESULTS: Histopathologic examination revealed perineural invasion in both tumors. CONCLUSION: This appears to be an unusual presentation of bilateral auricular SCCs with perineural invasion in an elderly immunocompromised patient. PMID- 11207702 TI - Liposuction Council Bulletin. PMID- 11207703 TI - Facial skin rejuvenation: laser resurfacing or chemical peel: choose your weapon. PMID- 11207704 TI - Chemical peeling vs. laser resurfacing. PMID- 11207705 TI - The use of combined nasolabial V-Y advancement and glabellar flaps for large medial canthal defects. AB - BACKGROUND: Reconstruction of the medial canthal area presents many challenges for surgeons. It has many functional and cosmetic peculiarities. The combined use of glabellar and nasolabial V-Y advancement flaps is an effective method for repairing large medial canthal defects. OBJECTIVE: To describe and illustrate a technique to repair medial canthal defects. METHODS: Our experience with combined usage of nasolabial V-Y flap and glabellar flaps for medial canthal closure after tumor resection in 23 patients is reported. RESULTS: All resections and reconstructive procedures were performed under local anesthesia. All patients were treated without any complications such as flap loss, wound dehiscence, lymphedema, or ectropion. Fine results were achieved from both the functional and aesthetic point of view. CONCLUSION: This combination has many advantages over skin grafts and other local flaps. It is easy to design, reliable, and offers good cosmetic results. This combination is recommended to plastic surgeons as a safe and effective procedure for reconstruction of medial the canthal area. PMID- 11207706 TI - Using suture removal kit for punch biopsy. PMID- 11207707 TI - Punch techniques, acne scarring, and resurfacing. PMID- 11207709 TI - Regarding surgical recontouring of the neck. PMID- 11207711 TI - The birth of Environmental Microbiology. PMID- 11207712 TI - Microbial diversity--the past and future of microbiology. In recognition of the centennial of the American Society for Microbiology. PMID- 11207713 TI - What makes Pseudomonas bacteria rhizosphere competent? PMID- 11207714 TI - The ecology of the myxobacteria. PMID- 11207715 TI - Inhibition of Escherichia coli precursor-16S rRNA processing by mouse intestinal contents. AB - The correlation between ribosome content and growth rate found in many bacterial species has proved useful for estimating the growth activity of individual cells by quantitative in situ rRNA hybridization. However, in dynamic environments, the stability of mature ribosomal RNA causes problems in using cellular rRNA contents for direct monitoring of bacterial growth activity in situ. In a recent paper, Cangelosi and Brabant suggested monitoring the content of precursors in rRNA synthesis (pre-rRNAs) as an alternative approach. These are rapidly broken down after the cessation of bacterial growth. We have applied fluorescence in situ hybridization of pre-16S rRNA to Escherichia coil cells growing in vitro in extracts from two different compartments of the mouse intestine: the caecal mucus layer, where E. coli grew rapidly, and the contents of the caecum, which supported much slower bacterial growth. The amounts of 23S rRNA and pre-16S rRNA measured for E. coil growing in intestinal mucus corresponded to that expected for bacteria with the observed growth rate. In contrast, the slow-growing E. coli cells present in intestinal contents turned out to have an approximately ninefold higher content of pre-16S rRNA than cultures of the same strain growing rapidly in rich media. We present results suggesting that the mouse intestinal contents contain an agent that inhibits the growth of E. coli by disturbing its ability to process pre-16S rRNA. PMID- 11207716 TI - Adaptive mgl-regulatory mutations and genetic diversity evolving in glucose limited Escherichia coli populations. AB - The mutational adaptation of E. coli to low glucose concentrations was studied in chemostats over 280 generations of growth. All members of six independent populations acquired increased fitness through the acquisition of mutations at the mgl locus, increasing the binding protein-dependent transport of glucose. These mutations provided a strong fitness advantage (up to 10-fold increase in glucose affinity) and were present in most isolates after 140 generations. mgl constitutivity in some isolates was caused by base substitution, short duplication, small deletion and IS1 insertion in the 1041 bp gene encoding the repressor of the mgl system, mglD (galS). But an unexpectedly large proportion of mutations were located in the short mgl operator sequence (mglO), and the majority of mutations were in mglO after 280 generations of selection. The adaptive mglO substitutions in several independent populations were at exactly the positions conserved in the two 8 bp half-sites of the mgl operator, with the nature of the base changes also completely symmetrical. Either mutations were directed to the operator or the particular operator mutations had a selective advantage under glucose limitation. Indeed, isolates carrying mglO mutations showed greater rates of transport for glucose and galactose at low concentrations than those carrying mglD null mutations. mglO mutations avoid cross-talk by members of the GalR-Lacl repressor family, reducing transporter expression and providing a competitive advantage in a glucose-limited environment. Another interesting aspect of these results was that each adapted population acquired multiple mgl alleles, with several populations containing at least six different mgl-regulatory mutations co-existing after 200 generations. The diversity of mutations in the mglO/mglD region, generally in combination with mutations at other loci regulating glucose uptake (malT, mlc, ptsG), provided evidence for multiple clones in each population. Increased fitness was accompanied by the generation of genetic diversity and not the evolution of a single winner clone, as predicted by the periodic selection model of bacterial populations. PMID- 11207717 TI - The generation of multiple co-existing mal-regulatory mutations through polygenic evolution in glucose-limited populations of Escherichia coli. AB - The multicomponent glucose transport system of Escherichia coli was used to study the polygenic basis of increased fitness in prolonged nutrient-limited, continuous cultures. After 280 generations of glucose-limited growth, nearly all bacteria in four independent chemostat populations exhibited increased glucose transport and contained multiple, stable mutations. Fitter bacteria increased outer membrane permeability for glucose through overexpression of the LamB glycoporin. Three classes of mutation influenced LamB levels as well as regulation of other mal genes. Low-level mal/lamB constitutivity resulted from mlc mutations acquired in all populations as well as changes at another uncharacterized locus. Larger increases in transporter content resulted from widespread acquisition of a regulatory malT-con mutation in fit isolates. The malT mutations sequenced from 67 adapted isolates were all single base substitutions resulting in amino acid replacements in the N-terminal third of the MalT activator protein. Analysis of malT-con sequences revealed a mutational spectrum distinct from that found in plate-selected malT mutants, suggesting that mutational pathways were affected by environmental factors. A second major finding was the remarkable allele diversity in malT within a population derived from a single clone, with at least 11 different alleles co-existing in a population. The multiplicity of alleles (as well as those found in adaptive mgl changes in the accompanying study) suggest that the periodic selection events observed previously in such populations are not a major factor in reducing genetic diversity. A simple model is presented for the generation of genetic heterogeneity in bacterial populations undergoing polygenic selection. PMID- 11207718 TI - Evidence for recent intergeneric transfer of a new tetracycline resistance gene, tet(W), isolated from Butyrivibrio fibrisolvens, and the occurrence of tet(O) in ruminal bacteria. AB - We have previously reported high-frequency transfer of tetracycline resistance between strains of the rumen anaerobic bacterium Butyrivibrio fibrisolvens. Donor strains were postulated to carry two TcR genes, one of which is transferred on a novel chromosomal element. It is shown here that coding sequences within the non transmissible gene in B. fibrisolvens 1.230 are identical to those of the Streptococcus pneumoniae tet(O) gene. This provides the first evidence for genetic exchange between facultatively anaerobic bacteria and rumen obligate anaerobes. In contrast, the product of the transmissible TcR gene shares only 68% amino acid sequence identity with the TetO and TetM proteins and represents a new class of ribosome protection tetracycline resistance determinant, designated Tet W. The tet(W) coding region shows a higher DNA G + C content (53%) than other B. fibrisolvens genes or other ribosome protection-type tet genes, suggesting recent acquisition from a high G + C content genome. Tet(W) genes with almost identical sequences are also shown to be present in TcR strains of B. fibrisolvens from Australian sheep and in TcR strains of two other genera of rumen obligate anaerobes, Selenomonas ruminantium and Mitsuokella multiacidus. This provides compelling evidence for recent intergeneric transfer of resistance genes between ruminal bacteria. Tet(W) is not restricted to ruminal bacteria, as it was also present in a porcine strain of M. multiacidus. PMID- 11207719 TI - Sulphate reduction and vertical distribution of sulphate-reducing bacteria quantified by rRNA slot-blot hybridization in a coastal marine sediment. AB - In the past, enumeration of sulphate-reducing bacteria (SRB) by cultivation-based methods generally contradicted measurements of sulphate reduction, suggesting unrealistically high respiration rates per cell. Here, we report evidence that quantification of SRB rRNA by slot-blot hybridization is a valuable tool for a more realistic assessment of SRB abundance in the natural environment. The distribution of SRB was investigated in a coastal marine sediment by hybridization of membrane-immobilized rRNA with oligonucleotide probes. As represented by general probe-target groups, SRB rRNA contributed between 18% and 25% to the prokaryotic rRNA pool. The dominant SRB were related to complete oxidizing genera (Desulphococcus, Desulphosarcina and Desulphobacterium), while Desulphobacter could not be detected. The vertical profile and quantity of rRNA from SRB was compared with sulphate reduction rates (SRR) measured with 35SO4(2-) tracer in whole-core incubations. While SRB abundance was highest near the surface, peaking at around 1.5 cm, measured sulphate reduction rates were lowest in this region. A second peak of SRB rRNA was observed at the transition zone from oxidized to reduced sediment, directly above the sulphate reduction maximum. Cell numbers calculated by converting the relative contribution of SRB rRNA to the percentage of DAPI-stained cells indicated a population size for SRB of 2.4 6.1 x 10(8) cells cm(-3) wet sediment. Cellular sulphate reduction rates calculated on the basis of these estimated cell numbers were between 0.01 and 0.09 fmol SO4(2-) cell(-1) day(-1), which is below the rates that have been determined for pure cultures (0.2-50 fmol SO4(2-) cell(-1) day(-1)) growing exponentially at nearoptimal temperature with a surplus of substrates. PMID- 11207720 TI - Functional analysis of the Pseudomonas syringae rulAB determinant in tolerance to ultraviolet B (290-320 nm) radiation and distribution of rulAB among P. syringae pathovars. AB - The effect of the plasmid-encoded rulAB (resistance to ultraviolet radiation) determinant on responses of Pseudomonas syringae to ultraviolet-B (UV-B) radiation and the distribution of rulAB among pathovars of P. syringae were determined. The cloned rulAB determinant and the native rulAB+ plasmid pPSR1 both conferred approximately a 10-fold increase in survival on P. syringae pv. syringae FF5 following increasing doses of UV-B radiation. rulAB+ P. syringae strains also maintained significantly larger epiphytic populations on leaf surfaces irradiated with UV-B. rulAB-insertional mutants, constructed in two native rulAB+ strains, were from 10- to 100-fold more sensitive to UV-B radiation. The UV tolerance phenotype and the rulAB genes were widely distributed among P. syringae pathovars isolated from varied plant hosts throughout the world and within a broad range of genotypic backgrounds of P. syringae pv. syringae. With one exception, the rulAB determinant was harboured on pPT23A-like plasmids; these replicons are indigenous residents of the species P. syringae and also tend to encode determinants of importance in host-pathogen interactions. PMID- 11207721 TI - Humics as an electron donor for anaerobic respiration. AB - The possibility that microorganisms might use reduced humic substances (humics) as an electron donor for the reduction of electron acceptors with a more positive redox potential was investigated. All of the Fe(III)- and humics-reducing microorganisms evaluated were capable of oxidizing reduced humics and/or the reduced humics analogue anthrahydroquinone-2,6,-disulphonate (AHODS), with nitrate and/or fumarate as the electron acceptor. These included Geobacter metallireducens, Geobacter sulphurreducens, Geothrix fermentans, Shewanella alga, Wolinella succinogenes and 'S. barnesii'. Several of the humics-oxidizing microorganisms grew in medium with AHQDS as the sole electron donor and fumarate as the electron acceptor. Even though it does not reduce Fe(III) or humics, Paracoccus denitrificans could use AHQDS and reduced humics as electron donors for denitrification. However, another denitrifier, Pseudomonas denitrificans, could not. AHODS could also serve as an electron donor for selenate and arsenate reduction by W. succinogenes. Electron spin resonance studies demonstrated that humics oxidation was associated with the oxidation of hydroquinone moieties in the humics. Studies with G. metallireducens and W. succinogenes demonstrated that the anthraquinone-2,6-disulphonate (AQDS)/AHQDS redox couple mediated an interspecies electron transfer between the two organisms. These results suggest that, as microbially reduced humics enter less reduced zones of soils and sediments, the reduced humics may serve as electron donors for microbial reduction of several environmentally significant electron acceptors. PMID- 11207722 TI - Electrokinetic movement of Escherichia coli in capillaries. AB - The movement of Escherichia coli K-12 has been studied in capillaries with an 8 microm inside diameter under a DC electric field. At low applied voltages (< 0.2 V cm(-1)), bacterial motility is the predominant mode of motion, with bacteria swimming, tumbling and moving unidirectionally towards the anode and the cathode, although a significant difference between the mean moving speeds towards the two electrodes was observed. When the electric field was removed, the mean swimming speeds were the same for both directions. At higher voltages, all the cells were swept by electro-osmotic flow exclusively towards the cathode. PMID- 11207723 TI - Biodegradation, plasmid-encoded catabolic pathways, host factors and cell metabolism. PMID- 11207724 TI - Biodegradation. PMID- 11207725 TI - Environmental microbiology--the second wave. PMID- 11207726 TI - Interactions between Clavibacter michiganensis and its host plants. PMID- 11207727 TI - Predicting biodegradation. AB - Biodegradation is important for natural and industrial cycling of environmental chemicals. Industries and government regulators increasingly seek to know the fate of chemicals in the environment and thus prevent potential negative impacts on human or ecosystem health. However, millions of organic compounds are known, and most will remain unstudied with respect to biodegradation. This necessitates the development of organized biodegradation information coupled with predictive methods. Biodegradation prediction methods are being developed using the information contained in the University of Minnesota Biocatalysis/ Biodegradation database. Heuristic rules are derived from compiled biodegradation information. Additional rules are generated by deconstructing compounds into a set of the 40 most common organic functional groups. The rules consist of deriving biochemically plausible catabolic reactions for each of the functional groups. More complex compounds, containing multiple functional groups, are analysed using higher order rules requiring prioritizing enzymatic attack and reactions cleaving functional groups. While biodegradation prediction, like weather prediction, will never be perfect, it can be an important tool for guiding industry, regulators and experimentalists. PMID- 11207728 TI - Phylogeny and in situ identification of a morphologically conspicuous bacterium, Candidatus Magnospira bakii, present at very low frequency in activated sludge. AB - A morphologically conspicuous bacterium that constituted a very small fraction (< 0.01%) of the total microbial community of activated sludge was enriched and analysed phylogenetically by a combination of cultivation-independent molecular and physical methods. The large, corkscrew-shaped, filamentous bacteria were first detected in municipal activated sludge by light microscopy owing to their unusual rotating gliding motility. Various attempts at microbiological enrichment and pure culture isolation with traditional techniques failed, as did attempts to retrieve the morphotype of interest by micromanipulation. In situ hybridization with the group-specific, rRNA-targeted oligonucleotide probe CF319a indicated a phylogenetic affiliation to the Cytophaga-Flexibacter group of the Cytophaga Flavobacterium-Bacteroides phylum. Based on strong morphological resemblance to members of the genus Saprospira, additional 16S rRNA-targeted oligonucleotides with more narrow specificity were designed and evaluated for in situ hybridization to the morphotype of interest. Flow cytometric cell sorting based on the fluorescence conferred by probe SGR1425 and forward scatter enabled a physical enrichment of the helical coiled cells. Subsequent polymerase chain reaction (PCR) amplification of 16S rDNA fragments from whole fixed sorted cells with a primer pair based on probes CF319a and SGR1425 resulted in the retrieval of 12 almost identical partial 16S rDNA fragments with sequence similarities among each other of more than 99.2%. In situ hybridizations proved that the sequences that showed the highest similarity (88.4%) to the 16S rRNA of Saprospira grandis were indeed retrieved from the corkscrew-shaped filaments. The bacterium is likely to be a member of a genus of which no species has been cultured hitherto. It was consequently tentatively named 'Magnospira bakii' and has the taxonomic rank of Candidatus Magnospira bakii, as the ultimate taxonomic placement has to await its cultivation. In this study, it was demonstrated that even bacteria occurring at very low frequencies in highly complex environmental samples can be retrieved selectively without cultivation for further molecular analysis. PMID- 11207729 TI - Application of nested polymerase chain reaction for the detection of as yet uncultured organisms of the class Actinobacteria in environmental samples. AB - Different groups of as yet uncultured, phylogenetically deeply rooting organisms of the class Actinobacteria have been shown previously by analysis of 16S rDNA clone libraries to be present in different soil and marine environments of worldwide distribution. In order to monitor specifically the occurrence of two of the actinobacterial groups among bacterial DNA extracted from different environments, a nested polymerase chain reaction (PCR) method, aiming at the sensitive detection of 16S rDNA, was used. Analysis of a clone library generated from one of these 16S rDNA-derived, group-specific PCR products of DNA from a forest soil broadened the spectrum of putative taxa within the two phylogenetic groups. Application of this PCR system demonstrated the presence of these organisms in natural environments and in a sample of dried and moistened peat. Fluctuations in the detectability of the target groups in different samples from the same site strongly suggest that the taxon diversity of a 16S rDNA clone library must be regarded as a temporal genomic snapshot taken from this environmental community. PMID- 11207730 TI - Anaerobic utilization of alkylbenzenes and n-alkanes from crude oil in an enrichment culture of denitrifying bacteria affiliating with the beta-subclass of Proteobacteria. AB - Denitrifying bacteria were enriched from freshwater sediment with added nitrate as electron acceptor and crude oil as the only source of organic substrates. The enrichment cultures were used as laboratory model systems for studying the degradative potential of denitrifying bacteria with respect to crude oil constituents, and the phylogenetic affiliation of denitrifiers that are selectively enriched with crude oil. The enrichment culture exhibited two distinct growth phases. During the first phase, bacteria grew homogeneously in the aqueous phase, while various C1-C3 alkylbenzenes, but no alkanes, were utilized from the crude oil. During the second phase, bacteria also grew that formed aggregates, adhered to the crude oil layer and emulsified the oil, while utilization of n-alkanes (C5 to C12) from the crude oil was observed. During growth, several alkylbenzoates accumulated in the aqueous phase, which were presumably formed from alkylbenzenes. Application of a newly designed, fluorescently labelled 16S rRNA-targeted oligonucleotide probe specific for the Azoarcus/Thauera group within the beta-subclass of Proteobacteria revealed that the majority of the enriched denitrifiers affiliated with this phylogenetic group. PMID- 11207731 TI - Methanogenic archaea and CO2-dependent methanogenesis on washed rice roots. AB - Washed excised roots of rice (Oryza sativa) immediately started to produce CH4 when they were incubated in phosphate buffer under anoxic conditions (N2 atmosphere), with initial rates varying between 2 and 70nmolh(-1)g(-1) dry weight of root material (mean +/- SE: 20.3 +/- 5.9 nmol h(-1) g(-1) dry weight; n = 18). Production of CH4 continued for at least 500 h, with rates usually decreasing slowly. CH4 production was not significantly affected by methyl fluoride, an inhibitor of acetoclastic methanogenesis. Less than 0.5% of added [2-14C]-acetate was converted to 14CH4, and conversion of 14CO2 to 14CH4 indicated that CH4 was almost exclusively produced from CO2. Occasionally, however, especially when the roots were incubated without additional buffer, CH4 production started to accelerate after about 200h reaching rates of > 100 nmol h(-1) g(-1) dry weight. Methyl fluoride inhibited methanogenesis by more than 20% only in these cases, and the conversion of 14CO2 to 14CH4 decreased. These results indicate that CO2 dependent rather than acetoclastic methanogenesis was primarily responsible for CH4 production in anoxically incubated rice roots. Determination of most probable numbers of methanogens on washed roots showed highest numbers (10(6)g(-1) dry roots) on H2 and ethanol, i.e. substrates that support CH4 production from CO2. Numbers on acetate (10(5) g(-1) dry roots) and methanol (10(4)g(-1) dry roots) were lower. Methanogenic consortia enriched on H2 and ethanol were characterized phylogenetically by comparative sequence analysis of archaeal small-subunit (SSU) ribosomal RNA-encoding genes (rDNA). These sequences showed a high similarity to SSU rDNA clones that had been obtained previously by direct extraction of total DNA from washed rice roots. The SSU rDNA sequences recovered from the H2/CO2 using consortium either belonged to a novel lineage of methanogens that grouped within the phylogenetic radiation of the Methanosarcinales and Methanomicrobiales or were affiliated with Methanobacterium bryantii. SSU rDNA sequences retrieved from the ethanol-using consortium either grouped within the genus Methanosarcina or belonged to another novel lineage within the phylogenetic radiation of the Methanosarcinales and Methanomicrobiales. Cultured organisms belonging to either of the two novel lineages have not been reported yet. PMID- 11207734 TI - Web alert. Mycology. An annotated selection of World Wide Web sites revelant to the topics environmental microbiology. PMID- 11207732 TI - Towards elucidation of microbial community metabolic pathways: unravelling the network of carbon sharing in a pollutant-degrading bacterial consortium by immunocapture and isotopic ratio mass spectrometry. AB - Although much information on metabolic pathways within individual organisms is available, little is known about the pathways operating in natural communities in which extensive sharing of nutritional resources is the rule. In order to analyse such a consortium pathway, we have investigated the flow of 4-chlorosalicylate as carbon substrate within a simple chemostat microbial community using 13C-labelled metabolites and isotopic ratio mass spectrometric analysis of label enrichment in immunocaptured member populations of the community. A complex pathway network of carbon sharing was thereby revealed, involving two different metabolic routes, one of which is completely novel and involves the toxic metabolite protoanemonin. The high stability of the community results, at least in part, from interdependencies based on carbon sharing and the rapid removal of toxic metabolites. PMID- 11207733 TI - A novel system for efficient gene expression and monitoring of bacteria in aquatic environments. AB - In a previous study, we reported the identification of Escherichia coli genes with increased expression in an aquatic environment. Here, we describe the use of one of these genes, gapC, as an expression system in freshwater habitats. We have identified the transcriptional start site of gapC and analysed the synthesis of the GapC protein during incubation in aquatic medium. The promoter of gapC was used to construct fusions to the reporter genes lacZ and gfp. Analysis of these fusions indicates the potential of gapC as a valuable tool for the detection of E. coli in freshwater habitats, as well as for expressing other genes in aquatic environments. PMID- 11207735 TI - Report on 1st Euroconference on Bacterial-Metal/Radionuclide Interactions: Basic Research and Bioremediation. PMID- 11207736 TI - An urgent need to reassess the balance between fundamental and applied environmental research. PMID- 11207737 TI - Improving human health means eliminating microbial pathogens. PMID- 11207738 TI - Multiple responses of gram-negative bacteria to organic solvents. PMID- 11207739 TI - Identification of the metabolically active members of a bacterial community in a polychlorinated biphenyl-polluted moorland soil. AB - The presumptive metabolically active members of a bacterial community in a moorland soil in Germany, highly polluted with polychlorinated biphenyls (PCBs), were identified by sequencing of cloned reverse transcription-polymerase chain reaction (RT-PCR) amplification products of 16S rRNA generated from total RNA extracts. Analysis of the 16S rRNA clone library revealed a considerable diversity of metabolically active bacteria in the soil, despite the acidic pH and high concentrations of PCBs. Cloned sequence types clustered within the Proteobacteria (34% alpha-, 33% beta- and 7% gamma-subclasses), the Holophaga Acidobacterium phylum (14%), the Actinobacteria (6.5%) and the Planctomycetales (2%). Three cloned sequence types were not affiliated to any described phylogenetic group. An unusual feature of this soil was the abundance of sequence types within the beta-subclass of the Proteobacteria, most of which were similar to the 16S rRNA gene sequences of species from only two genera, Burkholderia and Variovorax. Three other numerous 16S rRNA sequence types were similar to the sequences of Sphingomonas species, members of the Rhodopila globiformis group and Acidobacterium capsulatum. Some of the sequence types retrieved were similar to the 16S rRNA sequences of bacterial isolates able to degrade a variety of organic pollutants, including PCBs. As the PCB contamination is the major source of measurable carbon in this soil, some of the 16S rRNA sequence types detected and presumed to represent the metabolically active members of the community indicate the organisms likely to be involved, directly or indirectly, in the utilization of the PCBs as carbon and energy sources. PMID- 11207740 TI - Grazing of the copepod Diaptomus connexus on purple sulphur bacteria in a meromictic salt lake. AB - A meromictic lake ecosystem (Mahoney Lake, BC, Canada) was investigated to elucidate the significance of chemocline bacteria in the total carbon cycle under natural conditions. In this lake, primary production by oxygenic phototrophs was insufficient to support the observed net secondary production of the calanoid copepod Diaptomus connexus and the rotifer Brachionus plicatilis, indicating the presence of additional food sources for consumers. Mahoney Lake harbours the densest population of phototrophic sulphur bacteria ever reported in a natural body of water. This layer is located at the interface between oxic and anoxic water layers and is dominated by the purple sulphur bacterium Amoebobacter purpureus. The transfer rates of A. purpureus carbon to D. connexus determined in stratified mesocosms were very low (0.71 ngC copepod(-1) day(-1)) and accounted for only 0.6% of the observed net biomass increase in the zooplankter. Stable stratification within the mesocosms prevented an upwelling of A. purpureus into the oxic part. However, measurements of carbon fluxes, infrared fluorescence microscopy and stable carbon analysis provided cumulative evidence that, under in situ conditions, the cell carbon of purple sulphur bacteria indeed enters the aerobic food chain via the grazing activity of D. connexus. Based on a two-source isotopic mixing model, A. purpureus represents at least 75-85% of the diet of D. connexus. Autumnal upwelling into oxic water layers and aggregation of A. purpureus cells appear to be the main factors determining the high carbon flux from purple sulphur bacteria to zooplankton under natural conditions, and most probably also play a key role in other aquatic ecosystems. Through this pathway, over 53% of the reduced organic matter of purple sulphur bacteria trapped in anoxic bottom waters is returned to the oxic realm. PMID- 11207741 TI - Inhibition of photosynthesis and bleaching of zooxanthellae by the coral pathogen Vibrio shiloi. AB - Vibrio shiloi is the causative agent of bleaching (loss of endosymbiotic zooxanthellae) of the coral Oculina patagonica in the Mediterranean Sea. To obtain information on the mechanism of bleaching, we examined the effect of secreted material (AK1-S) produced by V. shiloi on zooxanthellae isolated from corals. AK1-S caused a rapid inhibition of photosynthesis of the algae, as measured with a Mini-PAM fluorometer. The inhibition of photosynthesis was caused by (i) ammonia produced during the growth of V. shiloi on protein-containing media and (ii) a non-dialysable heat-resistant factor. This latter material did not inhibit photosynthesis of the algae by itself but, when added to different concentrations of NH4Cl, enhanced the inhibition approximately two- to threefold. Ammonia and the enhancer were effective to different degrees on zooxanthellae isolated from four species of coral examined. In addition to the rapid inhibition of photosynthesis, AK1-S caused bleaching (loss of pigmentation) and lysis of zooxanthellae. Bleaching was more rapid than lysis, reaching a peak (25% bleached algae) after 6 h. The factors in AK1-S responsible for bleaching and lysis were different from those responsible for the inhibition of photosynthesis, because they were heat sensitive, non-dialysable and active in the dark. Thus, the coral pathogen V. shiloi produces an array of extracellular materials that can inhibit photosynthesis, bleach and lyse zooxanthellae. PMID- 11207742 TI - Microbial characterization of a JP-4 fuel-contaminated site using a combined lipid biomarker/polymerase chain reaction--denaturing gradient gel electrophoresis (PCR-DGGE)-based approach. AB - The impact of pollution on soil microbial communities and subsequent bioremediation can be measured quantitatively in situ using direct, non-culture dependent techniques. Such techniques have advantages over culture-based methods, which often account for less than 1% of the extant microbial community. In 1988, a JP-4 fuel spill contaminated the glacio-fluvial aquifer at Wurtsmith Air Force Base, Michigan, USA. In this study, lipid biomarker characterization of the bacterial and eukaryotic communities was combined with polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE) analysis of the eubacterial community to evaluate correlation between contaminant (JP-4 fuel) concentration and community structure shifts. Vadose, capillary fringe and saturated zone samples were taken from cores within and up- and down-gradient from the contaminant plume. Lipid biomarker analysis indicated that samples from within the plume contained increased biomass, with large proportions of typically gram negative bacteria. Outside the plume, lipid profiles indicated low-biomass microbial communities compared with those within the initial spill site. 16S rDNA sequences derived from DGGE profiles from within the initial spill site suggested dominance of the eubacterial community by a limited number of phylogenetically diverse organisms. Used in tandem with pollutant quantification, these molecular techniques should facilitate significant improvements over current assessment procedures for the determination of remediation end-points. PMID- 11207743 TI - Adaptation of Pseudomonas fluorescens to the plant rhizosphere. AB - Saprophytic Pseudomonas are common root-colonizing bacteria that can improve plant health. Efficient exploitation of these bacteria in agriculture requires knowledge of traits that enhance ecological performance in the rhizosphere. Here, I describe the development and application of a promoter-trapping technology (IVET) that enables the isolation of Pseudomonas fluorescens genes that show elevated levels of expression in the rhizosphere. Using IVET, 20 P. fluorescens genes were identified that are induced during rhizosphere colonization, and their patterns of expression were analysed in laboratory media and in the rhizosphere. Fourteen genes showed significant homology to sequences in GenBank that are involved in nutrient acquisition, stress response, or secretion; six showed no homology. Seven of the rhizosphere-induced (rhi) genes have homology to known non Pseudomonas genes. One of the rhi genes (hrcC) is a component of a type III secretion pathway, not previously known in non-parasitic bacteria. Together, these genes provide a view of the rhizosphere environment as perceived by a rhizosphere colonist, and suggest that the nature of the association between P. fluorescens and the plant root may be more complex and intimate than previously thought. PMID- 11207744 TI - rRNA probe-based cell fishing of bacteria. AB - We have developed a new, cultivation-independent, fast and flexible method for the rRNA-targeted probe-based enrichment of bacteria. The target cells were labelled by in situ hybridization with biotinylated polyribonucleotide probes. These probes were generated by in vitro transcription of amplified rDNA of a variable region in domain III of the 23S rRNA molecules. The probes were about 300 nucleotides in length and were labelled by incorporation of biotin-UTP during the transcription. Probes were hybridized with bacterial cells and incubated with paramagnetic streptavidin-coated particles. The labelled target cells can be separated in a column filled with steel wool inserted into the field of a permanent magnet. Unlabelled, non-target cells pass through the column, whereas labelled cells are retained. They were eluted from the column after removal of the magnetic field. Up to now, the method has been tested with mixtures of different pure cultures. For the first time, transcript probes have been used for the labelling of the target cells and for their specific separation. The enrichment of the target cells can be monitored by a streptavidin-fluorescein staining of the biotinylated target cells and/or by a subsequent in situ hybridization with fluorescently labelled oligonucleotide probes. Enrichment rates of up to 90-fold, depending on the original abundance of the cells of interest, could be determined. To demonstrate that the sorted cells were amenable to molecular analysis, we amplified and sequenced a part of the tuf gene of enriched Acinetobacter calcoaceticus cells. PMID- 11207746 TI - Post-modern ecology--is the environment the organism? PMID- 11207745 TI - Scientific basis for the bioremediation of the toxic spill of the Aznalcollar mine: combining bacteria and plants to address and intractable kind of pollution. PMID- 11207747 TI - Legionella: from environmental habitats to disease pathology, detection and control. AB - Studies on Legionella show a continuum from environment to human disease. Legionellosis is caused by Legionella species acquired from environmental sources, principally water sources such as cooling towers, where Legionella grows intracellularly in protozoa within biofilms. Aquatic biofilms, which are widespread not only in nature, but also in medical and dental devices, are ecological niches in which Legionella survives and proliferates and the ultimate sources to which outbreaks of legionellosis can be traced. Invasion and intracellular replication of L. pneumophila within protozoa in the environment play a major role in the transmission of Legionnaires' disease. Protozoa provide the habitats for the environmental survival and reproduction of Legionella species. L. pneumophila proliferates intracellularly in various species of protozoa within vacuoles studded with ribosomes, as it also does within macrophages. Growth within protozoa enhances the environmental survival capability and the pathogenicity (virulence) of Legionella. The growth requirements of Legionella, the ability of Legionella to enter a viable non culturable state, the association of Legionella with protozoa and the occurrence of Legionella within biofilms complicates the detection of Legionella and epidemiological investigations of legionellosis. Polymerase chain reaction (PCR) methods have been developed for the molecular detection of Legionella and used in environmental and epidemiological studies. Various physical and chemical disinfection methods have been developed to eliminate Legionella from environmental sources, but gaining control of Legionella in environmental waters, where they are protected from disinfection by growing within protozoa and biofilms, remains a challenge, and one that must be overcome in order to eliminate sporadic outbreaks of legionellosis. PMID- 11207748 TI - Dynamics of anoxygenic photosynthesis in an experimental green sulphur bacteria biofilm. AB - The dynamics of sulphide oxidation in an experimental biofilm of the green sulphur bacterium, Prosthecochloris aestuarii, were studied using a newly developed light-dark cycling procedure. The biofilm was grown for 6 weeks in a benthic gradient chamber, in which gradients of light, sulphide and oxygen were imposed experimentally. The H2S concentrations and pH were measured with microsensors as a function of depth in the biofilm and of time after a change in illumination status. The sulphide oxidation rates were calculated as a function of time and depth in the biofilm using a numerical procedure to solve the non stationary general diffusion equation. A close agreement was found between the areal rates of anoxygenic photosynthesis during the cycling procedure and the steady state before the cycling experiment. For the different layers of the biofilm, the maximum activity was observed after 10-12min of light exposure. After this maximum, sulphide oxidation decreased concomitantly with sulphide concentration, indicating sulphide limitation of anoxygenic photosynthesis. This lag time limits the application of the standard dark-light shift method with a brief light exposure of a few seconds and, therefore, the numerical procedure described in this study enables the depth distribution of anoxygenic photosynthesis rates in microbial mats to be determined more accurately. PMID- 11207749 TI - Molecular screening for alkane hydroxylase genes in Gram-negative and Gram positive strains. AB - We have developed highly degenerate oligonucleotides for polymerase chain reaction (PCR) amplification of genes related to the Pseudomonas oleovorans GPo1 and Acinetobacter sp. ADP1 alkane hydroxylases, based on a number of highly conserved sequence motifs. In all Gram-negative and in two out of three Gram positive strains able to grow on medium- (C6-C11) or long-chain n-alkanes (C12 C16), PCR products of the expected size were obtained. The PCR fragments were cloned and sequenced and found to encode peptides with 43.2-93.8% sequence identity to the corresponding fragment of the P. oleovorans GPo1 alkane hydroxylase. Strains that were unable to grow on n-alkanes did not yield PCR products with homology to alkane hydroxylase genes. The alkane hydroxylase genes of Acinetobacter calcoaceticus EB104 and Pseudomonas putida P1 were cloned using the PCR products as probes. The two genes allow an alkane hydroxylase-negative mutant of Acinetobacter sp. ADP1 and an Escherichia coli recombinant containing all P. oleovorans alk genes except alkB, respectively, to grow on n-alkanes, showing that the cloned genes do indeed encode alkane hydroxylases. PMID- 11207751 TI - Phylogenetic diversity of termite gut spirochaetes. AB - A molecular phylogenetic analysis was done of not-yet-cultured spirochaetes inhabiting the gut of the termite, Reticulitermes flavipes (Kollar). Ninety-eight clones of near-full-length spirochaetal 16S rDNA genes were classified by ARDRA pattern and by partial sequencing. All clones grouped within the genus Treponema, and at least 21 new species of Treponema were recognized within R. flavipes alone. Analysis of 190 additional clones from guts of Coptotermes formosanus Shiraki and Zootermopsis angusticollis (Hagen), as well as published data on clones from Cryptotermes domesticus (Haviland), Mastotermes darwiniensis Froggatt, Nasutitermes lujae (Wasmann) and Reticulitermes speratus(Kolbe), revealed a similar level of novel treponemal phylogenetic diversity in these representatives of five of the seven termite families. None of the clones was closely related (i.e. all bore < or = 91% sequence similarity) to any previously recognized treponeme. The data also revealed the existence of two major phylogenetic groups of treponemes: one containing all of the currently known isolates of Treponema and a large number of phylotypes from the human gingival crevice, but only a minority of the termite gut spirochaete clones; another containing the majority of termite spirochaete clones and two Spirochaeta (S. caldaria and S. stenostrepta), which, although free living, group within the genus Treponema on the basis of 16S rRNA sequence. Signature nucleotides that almost perfectly distinguished the latter group, herein referred to as the 'termite cluster', occurred at the following (E. coli numbering) positions: 289-G x C-311; A at 812; and an inserted nucleotide at 1273. The emerging picture is that the long-recognized and striking morphological diversity of termite gut spirochaetes is paralleled by their phylogenetic diversity and may reflect substantial physiological diversity as well. PMID- 11207750 TI - Reduction of (per)chlorate by a novel organism isolated from paper mill waste. AB - As part of a study on the microbiology of chlorate reduction, several new dissimilatory chlorate-reducing bacteria were isolated from a broad diversity of environments. One of these, strain CKB, was selected for a more complete characterization. Strain CKB was enriched and isolated from paper mill waste with acetate as the sole electron donor and chlorate as the sole electron acceptor. Strain CKB is a completely oxidizing, non-fermentative, Gram-negative, facultative anaerobe. Cells of strain CKB are 0.5 x 2 microm and are highly motile, with a single polar flagellum. In addition to acetate, strain CKB can use propionate, butyrate, lactate, succinate, fumarate, malate or yeast extract as electron donors, with chlorate as the sole electron acceptor. Strain CKB can also couple chlorate reduction to the oxidation of ferrous iron, sulphide, or the reduced form of the humic substances analogue 2,6-anthrahydroquinone disulphonate. Fe(II) is oxidized to insoluble amorphous Fe(II) oxide, whereas sulphide is oxidized to elemental sulphur. Growth is not associated with this metabolism, even when small quantities of acetate are added as a potential carbon source. In addition to chlorate, strain CKB can also couple acetate oxidation to the reduction of oxygen or perchlorate. Chlorate is completely reduced to chloride. Strain CKB has an optimum temperature of 35 degrees C, a pH optimum of 7.5 and a salinity optimum of 1% NaCl. Strain CKB can grow in chlorate and perchlorate concentrations of 80 or 20 mM respectively. Under anaerobic conditions, strain CKB can dismutate chlorite into chloride and O2, and is only the second organism shown to be capable of this metabolism. Oxidized minus reduced spectra of whole-cell suspensions of strain CKB showed absorbance maxima at 423, 523 and 552nm, which are indicative of the presence of c-type cytochrome(s). Analysis of the complete sequence of the 16S rDNA indicates that strain CKB is a member of the beta subclass of the Proteobacteria. The phototroph Rhodocyclus tenuis is the closest known relative. When tested, strain CKB could not grow by phototrophy and did not contain bacteriochlorophyll. Phenotypically and phylogenetically, strain CKB differs from all other described bacteria and represents the type strain of a new genus and species. PMID- 11207752 TI - Interaction between bacteriophage PBS1 and clay minerals and transduction of Bacillus subtilis by clay-phage complexes. AB - Bacteriophage PBS1 of Bacillus subtilis was rapidly adsorbed on montmorillonite (M) and kaolinite (K), and adsorption was maximal after 30min on both clays. There was no correlation between adsorption and the cation exchange capacity of the clays. Studies with sodium metaphosphate (a polyanion that interacts with positively charged sites on clay) indicated that positively charged sites on K were primarily responsible for the adsorption of the phage, whereas other mechanisms appeared to be involved in adsorption of the phage on M. X-ray diffraction and electron microscopic analyses showed that the phage partially intercalated M. Survival of the phage was increased by adsorption on the clays, and adsorbed phage maintained its ability to transduce bacterial cells for at least 30 days (the longest time studied) after the preparation of the clay-phage complexes. Electron microscopic observations indicated that transduction by the clay-phage complexes was primarily the result of the phage detaching from the clays in the presence of host cells. PMID- 11207753 TI - Novel bacterial endosymbionts of Acanthamoeba spp. related to the Paramecium caudatum symbiont Caedibacter caryophilus. AB - Acanthamoebae are increasingly being recognized as hosts for obligate bacterial endosymbionts, most of which are presently uncharacterized. In this study, the phylogeny of three Gram-negative, rod-shaped endosymbionts and their Acanthamoeba host cells was analysed by the rRNA approach. Comparative analyses of 16S rDNA sequences retrieved from amoebic cell lysates revealed that the endosymbionts of Acanthamoeba polyphaga HN-3, Acanthamoeba sp. UWC9 and Acanthamoeba sp. UWE39 are related to the Paramecium caudatum endosymbionts Caedibacter caryophilus, Holospora elegans and Holospora obtusa. With overall 16S rRNA sequence similarities to their closest relative, C. caryophilus, of between 87% and 93%, these endosymbionts represent three distinct new species. In situ hybridization with fluorescently labelled endosymbiont-specific 16S rRNA-targeted probes demonstrated that the retrieved 16S rDNA sequences originated from the endosymbionts and confirmed their intracellular localization. We propose to classify provisionally the endosymbiont of Acanthamoeba polyphaga HN-3 as 'Candidatus Caedibacter acanthamoebae', the endosymbiont of Acanthamoeba sp. strain UWC9 as 'Candidatus Paracaedibacter acanthamoebae' and the endosymbiont of Acanthamoeba sp. strain UWE39 as 'Candidatus Paracaedibacter symbiosus'. The phylogeny of the Acanthamoeba host cells was analysed by comparative sequence analyses of their 18S rRNA. Although Acanthamoeba polyphaga HN-3 clearly groups together with most of the known Acanthamoeba isolates (18S rRNA sequence type 4), Acanthamoeba sp. UWC9 and UWE39 exhibit <92% 18S rRNA sequence similarity to each other and to other Acanthamoeba isolates. Therefore, we propose two new sequence types (T13 and T14) within the genus Acanthamoeba containing, respectively, Acanthamoeba sp. UWC9 and Acanthamoeba sp. UWE39. PMID- 11207754 TI - Web alert. Microbial taxonomy. PMID- 11207755 TI - Probiotics and benefits to human health--the evidence in favour. PMID- 11207756 TI - Probiotics--snake oil for the new millennium? PMID- 11207757 TI - Application of molecular tools for in situ monitoring of bacterial growth activity. PMID- 11207758 TI - Development and characterization of a lux-modified 2,4-dichlorophenol-degrading Burkholderia sp. RASC. AB - lux-marked biosensors for assessing the toxicity and bioremediation potential of polluted environments may complement traditional chemical techniques. luxCDABE genes were introduced into the chromosome of the 2,4-dichlorophenol (2,4-DCP) mineralizing bacterium, Burkholderia sp. RASC c2, by biparental mating using the Tn4431 system. Experiments revealed that light output was constitutive and related to cell biomass concentration during exponential growth. The transposon insertion was stable and did not interrupt 2,4-DCP-degradative genes, and expression of luxCDABE did not constitute a metabolic burden to the cell. A bioluminescence response was detectable at sublethal 2,4-DCP concentrations: at < 10.26 microg ml(-1), bioluminescence was stimulated (e.g. 218% of control), but at concentrations >60 microg ml(-1) it declined to < 1%. Investigating the effect of [14C]-2,4-DCP concentration on the evolution of 14CO2 revealed that, for initial concentrations of 2.5-25 microg ml(-1), approximately equals 55% of the added 14C was mineralized after 24 h compared with <1% at 50 and 100 microg ml( 1). Inhibition of 2,4-DCP mineralization between 25 and 50 microg ml(-1) corresponded well to the EC50 value (33.83 microg ml(-1)) obtained from bioluminescence inhibition studies. lux-marked RASC c2 may therefore be used as a functionally (i.e. 2,4-DCP degrader) and environmentally relevant biosensor of toxicity and biodegradation inhibition. PMID- 11207759 TI - Molecular evidence for shifts in polysaccharide composition associated with adaptation of soybean Bradyrhizobium strains to the Brazilian Cerrado soils. AB - Pyrolysis mass spectrometry (PyMS) and DNA fingerprinting (RAPD and RSalpha hybridization) were used to characterize soybean inoculant strains and root nodule isolates of bradyrhizobia from the Brazilian Cerrado soils. Most isolates were shown to be derived from the inoculant strains on the basis of genotype comparisons by DNA fingerprinting. Phenotypic analysis (using PyMS) of the strains and separately of the polysaccharides derived from them showed that the nodule isolates differed from the parental strains, suggesting adaptation to the Cerrado soil environment. The extent of the differences between the derivatives and inoculant strains was similar for comparisons made on the basis of whole-cell preparations or from the isolated polysaccharides, indicating that the adaptation was caused by changes in the composition of the polysaccharides produced. PMID- 11207760 TI - 13C/12C isotope fractionation of aromatic hydrocarbons during microbial degradation. AB - The influence of microbial degradation on the 13C/12C isotope composition of aromatic hydrocarbons is presented using toluene as a model compound. Four different toluene-degrading bacterial strains grown in batch culture with oxygen, nitrate, ferric iron or sulphate as electron acceptors were studied as representatives of different environmental redox conditions potentially prevailing in contaminated aquifers. The biological degradation induced isotope shifts in the residual, non-degraded toluene fraction and the kinetic isotope fractionation factors alphaC for toluene degradation by Pseudomonas putida (1.0026 +/- 0.00017), Thauera aromatica (1.0017 +/- 0.00015), Geobacter metallireducens (1.0018 +/- 0.00029) and the sulphate-reducing strain TRM1 (1.0017 +/- 0.00016) were in the same range for all four species, although they use at least two different degradation pathways. A similar 13C/12C isotope fractionation factor (alphaC = 1.0015 +/- 0.00015) was observed in situ in a non sterile soil column in which toluene was degraded under sulphate-reducing conditions. No carbon isotope shifts resulting from soil-hydrocarbon interactions were observed in a non-degrading soil column control with aquifer material under the same conditions. The results imply that microbial degradation of toluene can produce a 13C/12C isotope fractionation in the residual hydrocarbon fraction under different environmental conditions. PMID- 11207761 TI - Anaerobic degradation of naphthalene by a pure culture of a novel type of marine sulphate-reducing bacterium. AB - Incubation of marine sediment in anoxic, sulphate-rich medium in the presence of naphthalene resulted in the enrichment of sulphate-reducing bacteria. Pure cultures with short, oval cells (1.3 by 1.3-1.9 microm) were isolated that grew with naphthalene as the only organic carbon source and electron donor for sulphate reduction to sulphide. One strain, NaphS2, was characterized. It affiliated with completely oxidizing sulphate-reducing bacteria of the delta subclass of the Proteobacteria, as revealed by 16S rRNA sequence analysis. 2 Naphthoate, benzoate, pyruvate and acetate were used in addition to naphthalene. Quantification of substrate consumption, sulphide formation and formed cell mass revealed that naphthalene was completely oxidized with sulphate as the electron acceptor. PMID- 11207762 TI - Environmental and clinical isolates of Pseudomonas aeruginosa show pathogenic and biodegradative properties irrespective of their origin. AB - Virulence properties of pathogenic bacteria, as well as resistance to antibiotics, are thought to arise through a specialization process favoured by the strong selection pressure imposed in clinical treatments. Nevertheless, in the case of opportunistic pathogens, it is unclear whether strains can be classified into virulent and non-virulent isolates. Clones of the opportunistic pathogen Pseudomonas aeruginosa do not seem to be associated to a particular biovar or pathovar, which suggests that virulence characteristics in opportunistic pathogens may already be present in environmental (non-clinical) isolates. We have explored this possibility, studying environmental isolates (mainly from oil-contaminated soils) and clinical isolates (from bacteraemia and cystic fibrosis patients) of P. aeruginosa. All environmental strains were found to actively efflux quinolones, which are synthetic antibiotics not expected to be present in the environment. These strains contained multidrug resistance determinants, were capable of invading epithelial cells and presented genes from the quorum-sensing and type III secretion systems. Some of them expressed either haemolytic or proteolytic activities or both, characteristics considered to be typical of virulent strains. All the strains tested, of clinical or environmental origin, could use alkanes (oil hydrocarbons) as a carbon source. Our results suggest that clinical and non-clinical P. aeruginosa strains might be functionally equivalent in several traits relevant for their virulence or environmental properties. Selection of clinically relevant traits, such as antibiotic resistance or cellular invasiveness, in opportunistic pathogens present in soil ecosystems is discussed. PMID- 11207763 TI - Host specificity in the Richelia-diatom symbiosis revealed by hetR gene sequence analysis. AB - The filamentous heterocyst-forming cyanobacterium Richelia intracellularis forms associations with diatoms and is very abundant in tropical and subtropical seas. The genus Richelia contains only one species, R. intracellularis Schmidt, although it forms associations with several diatom genera and has considerable variation in size and morphology. The genetic diversity, and possible host specificity, within the genus Richelia is unknown. Using primers against hetR, a gene unique for filamentous cyanobacteria, specific polymerase chain reaction (PCR) products were obtained from natural populations of R. intracellularis filaments associated with three diatom genera. Phylogenetic analyses of these sequences showed that they were all in the same clade. This clade contained only the R. intracellularis sequences. The genetic affiliation of hetR sequences of R. intracellularis to those of other heterocystous cyanobacteria strongly suggests that it was not closely related to endosymbiotic Nostoc spp. hetR sequences. Sequences from R. intracellularis-Hemiaulus membranaceus sampled in the Atlantic and Pacific Oceans were almost identical, demonstrating that the genetic relatedness was not dependent on geographical location. All sequences displayed a deep divergence between symbionts from different genera and a high degree of host specificity. PMID- 11207764 TI - Tomato seed and root exudate sugars: composition, utilization by Pseudomonas biocontrol strains and role in rhizosphere colonization. AB - The role of tomato seed and root exudate sugars as nutrients for Pseudomonas biocontrol bacteria was studied. To this end, the major exudate sugars of tomato seeds, seedlings and roots were identified and quantified using high-performance liquid chromatographic (HPLC) analysis. Glucose, fructose and maltose were present in all studied growth stages of the plant, but the ratios of these sugars were strongly dependent on the developmental stage. In order to study the putative role of exudate sugar utilization in rhizosphere colonization, two approaches were adopted. First, after co-inoculation on germinated tomato seeds, the root-colonizing ability of the efficient root-colonizing P. fluorescens strain WCS365 in a gnotobiotic quartz sand-plant nutrient solution system was compared with that of other Pseudomonas biocontrol strains. No correlation was observed between the colonizing ability of a strain and its ability to use the major exudate sugars as the only carbon and energy source. Secondly, a Tn5lacZ mutant of P. fluorescens strain WCS365, strain PCL1083, was isolated, which is impaired in its ability to grow on simple sugars, including those found in exudate. The mutation appeared to reside in zwf, which encodes glucose-6 phosphate dehydrogenase. The mutant grows as well as the parental strain on other media, including tomato root exudate. After inoculation of germinated sterile tomato seeds, the mutant cells reached the same population levels at the root tip as the wild-type strain, both alone and in competition, indicating that the ability to use exudate sugars does not play a major role in tomato root colonization, despite the fact that sugars have often been reported to represent the major exudate carbon source. This conclusion is supported by the observation that the growth of mutant PCL1083 in vitro is inhibited by glucose, a major exudate sugar, at a concentration of 0.001%, which indicates that the glucose concentration in the tomato rhizosphere is very low. PMID- 11207765 TI - The formation of migratory ripples in a mixed species bacterial biofilm growing in turbulent flow. AB - Mixed-species biofilms, consisting of Klebsiella pneumoniae, Pseudomonas aeruginosa, Pseudomonas fluorescens and Stenotrophomonas maltophilia, were grown in glass flow cells under either laminar or turbulent flow. The biofilms grown in laminar flow consisted of roughly circular-shaped microcolonies separated by water channels. In contrast, biofilm microcolonies grown in turbulent flow were elongated in the downstream direction, forming filamentous 'streamers'. Moreover, biofilms growing in turbulent flow developed extensive patches of ripple-like structures between 9 and 13 days of growth. Using time-lapse microscopic imaging, we discovered that the biofilm ripples migrated downstream. The morphology and the migration velocity of the ripples varied with short-term changes in the bulk liquid flow velocity. The ripples had a maximum migration velocity of 800 micromh(-1) (2.2 x 10(-7) m s(-1)) when the liquid flow velocity was 0.5 ms(-1) (Reynolds number=1,800). This work challenges the commonly held assumption that biofilm structures remain at the same location on a surface until they eventually detach. PMID- 11207766 TI - Effect of temperature on sulphate reduction, growth rate and growth yield in five psychrophilic sulphate-reducing bacteria from Arctic sediments. AB - Five psychrophilic sulphate-reducing bacteria (strains ASv26, LSv21, PSv29, LSv54 and LSv514) isolated from Arctic sediments were examined for their adaptation to permanently low temperatures. All strains grew at -1.8 degrees C, the freezing point of sea water, but their optimum temperature for growth (T(opt)) were 7 degrees C (PSv29), 10 degrees C (ASv26, LSv54) and 18 degrees C (LSv21, LSv514). Although T(opt) was considerably above the in situ temperatures of their habitats (-1.7 degrees C and 2.6 degrees C), relative growth rates were still high at 0 degrees C, accounting for 25-41% of those at T(opt). Short-term incubations of exponentially growing cultures showed that the highest sulphate reduction rates occurred 2-9 degrees C above T(opt). In contrast to growth and sulphate reduction rates, growth yields of strains ASv26, LSv54 and PSv29 were almost constant between -1.8 degrees C and T(opt). For strains LSv21 and LSv514, however, growth yields were highest at the lowest temperatures, around 0 degrees C. The results indicate that psychrophilic sulphate-reducing bacteria are specially adapted to permanently low temperatures by high relative growth rates and high growth yields at in situ conditions. PMID- 11207767 TI - Web alert. Microscopy of microorganisms. PMID- 11207768 TI - Bacillus subtilis macrofibres, colonies and bioconvection patterns use different strategies to achieve multicellular organization. PMID- 11207769 TI - Cell envelope mutants of Pseudomonas putida: physiological characterization and analysis of their ability to survive in soil. AB - To generate mutants with altered lipopolysaccharides (LPS) of the wild-type Pseudomonas putida KT2442, we used the mini-Tn5luxAB-Km transposon. A mutant was found among luminescent colonies and selected as a negative clone in enzyme linked immunosorbent assay (ELISA) with monoclonal antibody (mAb) 7.3B, which recognizes the O-antigen of P. putida LPS. The DNA region of the LPS mutant interrupted by the minitransposon insertion was cloned and sequenced. Comparison of the deduced amino acid sequence with protein sequence databases showed similarity to the O-antigen polymerase (Wzy) of Salmonella enterica (muenchen). The wild-type gene was rescued by polymerase chain reaction (PCR), cloned into a broad-host-range plasmid and used to carry out complementation assays. The cloned gene was able to restore the wild-type phenotype of the P. putida wzy mutant. We constructed an isogenic mutant of the luminescent wzy mutant to which an oprL mutation was transferred by homologous recombination with an oprL::xylE cassette. The wzy mutants of P. putida were more sensitive to SDS, deoxycholate and EDTA than the corresponding parental strains. We analysed the ability of wzy, oprL and wzy oprL mutants of P. putida to colonize soil. In comparison with the wild-type strain, the ability of single mutants to colonize soil decreased; this characteristic was more evident for the double mutant, especially at high temperatures. PMID- 11207770 TI - Aerotaxis in Desulfovibrio. AB - Aerotaxis of two sulphate-reducing bacteria, the freshwater strain Desulfovibrio desulfuricans CSN (DSM 9104) and the marine strain Desulfovibrio oxyclinae N13 (DSM 11498), was studied using capillary microslides, microscopy and oxygen microsensors. The bacteria formed ring-shaped bands in oxygen diffusion gradients surrounding O2 bubbles, which were placed into anoxic sulphate-free cell suspensions in capillary microslides. The radial expansion of the oxic volume by diffusion was stopped by aerobic respiration. Bands were formed by cells avoiding high O2 levels near the O2 bubble, as well as by cells entering from the surrounding anoxic zone. At the inner edge of the bands, O2 levels of up to 20% air saturation (50 microM O2) were found, while the outer edge always coincided with the oxic-anoxic interface. Ring diameters and O2 concentrations at the inner edge of the band depended on the cell density and the strain used in the suspension. Band formation did not occur in the absence of an electron donor (5mM lactate) or when N2 gas bubbles were used. Both strains were highly motile with velocities of approximately equals 32 microm s(-1) during forward runs, and 7 microm s(-1) during backward runs respectively. Within the bands, cells moved in circles of about 20 microm diameter, while cells outside the band exhibited straighter or only slightly bent traces. It is concluded that the capacity of respiration at high rates and the positive and negative aerotactical responses of Desulfovibrio provide an efficient strategy for removing O2 from the habitat in situations where sufficient electron donors and high cell densities are present. PMID- 11207771 TI - Signalling by the fungus Pythium ultimum represses expression of two ribosomal RNA operons with key roles in the rhizosphere ecology of Pseudomonas fluorescens F113. AB - Pseudomonas fluorescens F113 produces antifungal metabolites that protect the roots of sugarbeet from the fungus Pythium ultimum. The phytopathogen, in turn, has the ability to downregulate the expression of genes fundamental to the rhizosphere competence of the bacterial strain. This paper describes the characterization of two of these genes, which were isolated by screening a mini Tn5::lacZ mutant bank for differential expression of beta-galactosidase in the presence of P. ultimum. In order to identify the genes affected in reporter mutants SF3 and SF5, the transposons and flanking regions were cloned. Sequence analysis of the regions flanking the transposons in SF3 revealed that mini Tn5::lacZ had inserted into a tRNA(Ile) gene, which maps within a ribosomal RNA (rrn) operon. In SF5, the transposon inserted between the promoter of a second rrn operon and a gene encoding a 16S rRNA. Southern blot analysis demonstrated that there are five rrn operons in P. fluorescens F113 and that the transposons in SF3 and SF5 had inserted into two different operons. Further characterization of these mutants suggests that their reduced rhizosphere competence is not the result of reduced viability in the short term but may be accounted for partly by reduced growth rates under conditions that support rapid growth. Analysis of lacZ expression in the reporter mutants indicate that the marked rrn operons are regulated differently, suggesting different physiological roles. PMID- 11207772 TI - Climatic influence on mesophilic Bacillus cereus and psychrotolerant Bacillus weihenstephanensis populations in tropical, temperate and alpine soil. AB - Bacillus weihenstephanensis strains are psychrotolerant and grow from below 7 degrees C to 38 degrees C. Closely related mesophilic Bacillus cereus strains can grow from above 7 degrees C to 46 degrees C. We classified 1060 B. cereus group isolates from different soil samples with respect to their psychrotolerant and mesophilic genotypes by polymerase chain reaction (PCR) targeting of specific 16S rDNA and cold shock protein A gene signatures. In parallel, growth tests at 7 degrees C were carried out to determine the thermal phenotype. The geographic distribution of psychrotolerant and mesophilic isolates was found to depend significantly on the prevalent annual average temperature. In one tropical, one temperate and two alpine habitats, the proportion of psychrotolerant cspA genotypes was found to be 0%, 45% and 86% and 98%, respectively, with the corresponding annual average temperatures being 28 degrees C, 7 degrees C, 4 degrees C and 1 degrees C. In the tropical habitat, only the mesophilic B. cereus was found, characterized by correspondence of thermal genotype and phenotype. In the alpine habitat, almost only the psychrotolerant B. weihenstephanensis was isolated. In the temperate habitat, mesophilic B. cereus and psychrotolerant B. weihenstephanensis as well as 'intermediate thermal types' occurred, the latter having opposite thermal genotypes and phenotypes or opposing sets of thermal DNA signatures, characterized by the coexistence of mesophilic and psychrotolerant 16S rDNA operon copies within a single isolate. Both sugar utilization and DNA fingerprinting patterns revealed a high, probably non-clonal microsite diversity within the population of the temperate habitat. We interpret our observations in terms of a temperature-dependent selection regime, acting on recombining B. cereus/ B. weihenstephanensis populations in soil. PMID- 11207773 TI - Fluorescence in situ hybridization analysis of the prokaryotic community inhabiting crystallizer ponds. AB - A fluorescence in situ hybridization (FISH) protocol suitable for the identification of prokaryotes inhabiting hypersaline environments was developed and applied to several crystallizer ponds with salinities above 36% from a multipond solar saltern in Alicante, Spain. Two morphotypes were abundant in these environments: rods and square or square-like prokaryotes that could be affiliated to Bacteria and Archaea, respectively, by FISH with domain-specific probes. FISH with a newly designed probe proved that the archaeal 16S rDNA sequence most frequently recovered from the crystallizers, SPhT, originated from the dominant square-like prokaryotes. These uncultured prokaryotes have the morphology of Walsby's square bacteria. Additionally, FISH with a probe targeted to the genus Haloarcula, members of which are frequently isolated from this environment, indicated that this genus accounts for less than 0.1% of the total prokaryotic community. PMID- 11207775 TI - The hexY genes of Erwinia carotovora ssp. carotovora and ssp. atroseptica encode novel proteins that regulate virulence and motility co-ordinately. AB - Mutations located in a new gene, hexY, in Erwinia carotovora ssp. carotovora (Ecc) and ssp. atroseptica (Eca) cause strong upregulation of production of exoenzyme virulence factors and motility. The hexY gene encodes a novel 14.4 kDa protein with no known homologues. The hexY mRNA transcript has an unusually long (525bp) 5' untranslated region, which may be important for post-transcriptional regulation. An elevated level of transcription of two exoenzyme genes, pelCand celV, was observed in the HexY mutant background. The levels of cellulase and protease in a HexY mutant were independent of the presence of PGA, suggesting a role for HexY in the induction of these enzymes seen upon PGA addition. Electron microscopy revealed that HexY cells were hyperflagellated, perhaps contributing to the hypermotility phenotype of this mutant. The HexY mutant M5 exhibited enhanced maceration capacity on potato tubers. Therefore, the hexY gene and its gene product may define another level of regulation of virulence determinants in Ecc and Eca. PMID- 11207776 TI - Web alert. Microbial ecology. PMID- 11207774 TI - Co-evolution between Frankia populations and host plants in the family Casuarinaceae and consequent patterns of global dispersal. AB - Symbioses between the root nodule-forming, nitrogen-fixing actinomycete Frankia and its angiospermous host plants are important in the nitrogen economies of numerous terrestrial ecosystems. Molecular characterization of Frankia strains using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) analyses of the 16S rRNA-ITS gene and of the nifD-nifK spacer was conducted directly on root nodules collected worldwide from Casuarina and Allocasuarina trees. In their native habitats in Australia, host species contained seven distinctive sets of Frankia in seven different molecular phylogenetic groups. Where Casuarina and Allocasuarina trees are newly planted outside Australia, they do not normally nodulate unless Frankia is introduced with the host seedling. Nodules from Casuarina trees introduced outside Australia over the last two centuries were found to contain Frankia from only one of the seven phylogenetic groups associated with the host genus Casuarina in Australia. The phylogenetic group of Frankia found in Casuarina and Allocasuarina trees introduced outside Australia is the only group that has yielded isolates in pure culture, suggesting a greater ability to survive independently of a host. Furthermore, the Frankia species in this group are able to nodulate a wider range of host species than those in the other six groups. In baiting studies, Casuarina spp. are compatible with more Frankia microsymbiont groups than Allocasuarina host spp. adapted to drier soil conditions, and C. equisetifolia has broader microsymbiont compatibility than other Casuarina spp. Some Frankia associated with the nodular rhizosphere and rhizoplan, but not with the nodular tissue, of Australian hosts were able to nodulate cosmopolitan Myrica plants that have broad microsymbiont compatibility and, hence, are a potential host of Casuarinaceae infective Frankia outside the hosts' native range. The results are consistent with the idea that Frankia symbiotic promiscuity and ease of isolation on organic substrates, suggesting saprophytic potential, are associated with increased microsymbiont ability to disperse and adapt to diverse new environments, and that both genetics and environment determine a host's nodular microsymbiont. PMID- 11207779 TI - Advances in neuroimaging: surgical localization. PMID- 11207780 TI - Changes in nitric oxide synthesis and epileptic activity in the contralateral hippocampus of rats following intrahippocampal kainate injection. AB - PURPOSE: To investigate the effects of nitric oxide (NO) on seizure activity observed in brain areas that are remote from a primary epileptic focus. METHODS: Following an injection of kainate (concentration 1 mg/ml, volume 1 microl) in the rat hippocampus, we measured NO synthesis in the contralateral hippocampus and epileptic activity by electroencephalogram (EEG). The NO end products, nitrite and nitrate, were measured by in vivo microdialysis combined with an automated NO end-product analyzer and then used as indices of NO synthesis. We also assessed the effect of a specific inhibitor of neuronal NO synthase (NOS) on both the epileptic activity and NO synthesis in the contralateral hippocampus. For this assessment, we administered 7-nitroindazole (7-NI) (50 mg/kg) intraperitoneally 30 min before the kainate injection. RESULTS: Epileptic discharges in the contralateral hippocampus were frequently observed 90 min after unilateral hippocampus kainate injection. The duration of these discharges gradually increased until 240 min after the kainate injection. The NO end-product levels increased immediately after kainate injection and continued to increase gradually throughout the experiments, to a maximum of 213% of the base level. This elevation of NO end products was followed by epileptic discharges. Both the seizure activity and the elevation of contralateral hippocampus NO end-product levels were markedly attenuated in the animals that received 7-NI. CONCLUSIONS: The results suggest that remote seizure activity caused by the transneuronal spread of kainate-induced discharges may be related to NO derived from neuronal NOS. PMID- 11207781 TI - Postictal diffusion-weighted imaging for the localization of focal epileptic areas in temporal lobe epilepsy. AB - PURPOSE: Diffusion-weighted MR imaging (DWI) is a novel technique to delineate focal areas of cytotoxic edema of various etiologies. We hypothesized that DWI may also detect the epileptogenic region and adjacent areas during the ictal and early postictal periods in patients with temporal lobe epilepsy (TLE). METHODS: We studied patients with intractable TLE (n = 9), due to hippocampal sclerosis (HS, n = 7), left mesial temporal lobe tumor (n = 1), and of unknown etiology (n = 1). Informed consent was obtained before inclusion in the study. All patients with single short seizures were scanned immediately after EEG-documented seizures (between 45 and 150 min); one of two patients in status was scanned 14 h after cessation of seizures. DWI results were analyzed visually and by calculating apparent diffusion coefficient (ADC) maps. RESULTS: We found significant decreases in ADC postictally in one of six patients with TLE due to HS and single short seizures. One patient with an incompletely resected temporal lobe tumor also exhibited ADC abnormalities. One patient in focal status epilepticus revealed a decrease in ADC, and one patient with a continuous aura had no DWI abnormality. CONCLUSIONS: Postictal DWI technique may occasionally help delineate epileptic areas in some patients with TLE. Yield is low in patients with HS and single short seizures: it may be higher in patients with tumor or status epilepticus. PMID- 11207782 TI - Effects of vigabatrin on brain GABA+/CR signals in patients with epilepsy monitored by 1H-NMR-spectroscopy: responder characteristics. AB - PURPOSE: Vigabatrin (VGB) is a new antiepileptic drug that increases the human brain gamma-aminobutyric acid (GABA) level by irreversibly inhibiting GABA transaminase. Although some patients respond to VGB with a significant seizure reduction, others do not. The aim of this study was to identify possible responders before or in an early phase of VGB treatment by measuring the GABA and homocarnosine contaminated with macromolecules/creatine and phosphocreatine ratio (GABA+/Cr) signal by means of proton-nuclear magnetic resonance (1H NMR) spectroscopy. METHODS: Measurements were performed immediately before and after a titration period of 1 month (2 g/day during the past 2 weeks). A third measurement followed a maintenance period of 3 months (2 or 3 g/day). In 14 patients with drug-resistant temporal lobe epilepsy and 3 patients with occipital lobe epilepsy, GABA+/Cr was measured in the ipsilateral (i.e., epileptogenic) hemisphere and contralateral (i.e., nonepileptogenic) hemisphere in a volume of 8 cm3. RESULTS: Depending on the therapeutic efficacy of VGB, we defined three groups: (a) full responders (n = 7), (b) nonresponders (n = 7), and (c) partial responders (n = 3). The nonresponders had no significant change in the GABA+/Cr signal during the treatment compared with baseline. The full responders had a significant increase of the GABA+/Cr signal during the whole treatment phase and a lower ipsilateral level at baseline. The partial responders had also a lowered ipsilateral GABA+/Cr signal at baseline and an increase during treatment but a decrease when the seizures started again. CONCLUSIONS: Responders to VGB could be identified by a lower ipsilateral baseline GABA+/Cr signal and a steeper increase during VGB treatment. However, it was not possible to predict the duration of the response (full versus partial responder) with these criteria. PMID- 11207783 TI - Magnetic resonance spectroscopy and histopathological findings in temporal lobe epilepsy. AB - PURPOSE: In some patients with temporal lobe epilepsy, histopathological evaluation of resected brain tissue after surgical treatment may reveal several features indicative of discrete cortical malformations. We sought to determine whether these histopathological features were accompanied by hippocampal changes detectable preoperatively by proton magnetic resonance (MR) spectroscopy and to evaluate their relationship with postoperative outcome. METHODS: In 25 consecutive temporal lobe epilepsy patients who were scheduled for surgical treatment, MR spectroscopy was performed, and resected brain tissue was analyzed histopathologically for the presence of discrete cortical malformations (e.g., microdysgenesis). Outcome was assessed in all patients with an average postoperative period of 26 months. RESULTS: In 13 patients, we found subtle, histopathologically detectable signs of cortical malformation: 6 of them with concomitant hippocampal sclerosis (dual pathology) and 7 without. The latter subgroup had a worse surgical outcome and showed enhanced bilateral and/or contralateral pathological changes in the hippocampal formation when investigated by MR spectroscopy. CONCLUSIONS: These data suggest that by showing contralaterally or bilaterally abnormal spectra, MR spectroscopy might be able to indicate pathological changes in subtle developmental disorders that are possibly more widespread over the brain. This observation may improve noninvasive diagnosis in presurgical evaluation and the neurobiological understanding of cortical malformations in pharmacoresistant temporal lobe epilepsy. PMID- 11207784 TI - Short-term outcomes of children with febrile status epilepticus. AB - Febrile status epilepticus (SE) represents the extreme end of the complex febrile seizure spectrum. If there are significant sequelae to febrile seizures, they should be more common in this group. We have prospectively identified 180 children aged 1 month to 10 years who presented with febrile SE over a 10-year period in Bronx, New York, and Richmond, Virginia. They were compared with 244 children who presented with their first febrile seizure (not SE) in a prospective study done in the Bronx. The mean age of the children with febrile SE was 1.92 years, and of the comparison group, 1.85 years. Duration of SE was 30-59 min in 103 (58%), 60-119 min in 43 (24%), and > or =120 min in 34 (18%). Focal features were present in 64 (35%) of cases. There were no deaths and no cases of new cognitive or motor handicap. Children with febrile SE were more likely to be neurologically abnormal (20% vs. 5%; p < 0.001), to have a history of neonatal seizures (3% vs. 0; p = 0.006) and a family history of epilepsy (11% vs. 5%; p = 0.05) and less likely to have a family history of febrile seizures (15% vs. 27%; p = 0.01) than were children in the comparison group. The short-term morbidity and mortality of febrile SE are low. There are differences in the types of children who have febrile SE compared with those who experience briefer febrile seizures. Long-term follow-up of this cohort may provide insight into the relationship of prolonged febrile seizures and subsequent mesial temporal sclerosis. PMID- 11207786 TI - Visual symptoms in epilepsy and migraine: localization and patterns. AB - PURPOSE: To clarify differences in the localization of visual symptom patterns in epilepsy and migraine, we analyzed patient-generated illustrations of visual symptoms. METHODS: Patients were asked to draw their visual symptoms from memory using marker pens of 12 colors. All patients illustrated their symptoms on a template sheet representing the binocular visual field. We analyzed a total of 67 illustrations from 54 patients aged 6-40 years: 28 with epilepsy, 23 with migraine, and 3 with migraine-epilepsy syndrome. RESULTS: With respect to positive visual manifestations, those of epileptic patients were predominantly centrally localized (20 of 24, 83%), whereas those of migraine patients were predominantly peripherally localized (10 of 13, 77%) (p < 0.0001). With respect to negative visual symptoms, those in epilepsy were commonly diffuse (10 of 14, 71%) compared with those in migraine, which were peripheral (9 of 12, 75%) (p < 0.05). CONCLUSIONS: Results of this study suggest that the localization of visual symptoms differs between epilepsy and migraine. PMID- 11207785 TI - The role of vigabatrin in childhood seizure disorders: results from a clinical audit. AB - PURPOSE: The emergence of visual field defects attributed to vigabatrin (VGB) treatment and intramyelinic edema in animal experiments has raised concerns about its future role in the treatment of childhood seizures. METHODS: We evaluated our experience with this antiepileptic agent with retrospective analysis of database and chart audit. RESULTS: Of 73 patients, 43 girls and 33 boys were treated with VGB over a 7-year period. The mean age of patients at the introduction of VGB was 87 months (range, 5-257 months). In 12 of 73 cases, VGB was used as monotherapy; in 61 of 73 cases, it was used as an add-on drug. Seizure types included secondarily generalized seizures (21), mixed seizures (21), partial seizures (18), and generalized seizures (13). Seizure etiology was idiopathic/cryptogenic in 22 patients, symptomatic in 50, and undetermined in a single patient. The mean duration of therapy was 16 months (median, 10 months; range, 1-144 months). VGB was effective in 30 (seven seizure free, 23 with >90% reduction in seizures), partially effective in four (50-90% reduction in seizures), and ineffective in 38 (<50% reduction in seizures). Nearly 50% of patients with infantile spasms responded to VGB. All patients underwent ophthalmic evaluation; two (16%) of 12 patients who could undergo static threshold perimetry were demonstrated to have the characteristic visual field constriction. CONCLUSIONS: VGB is effective in producing a significant reduction in seizure frequency in nearly half the patients with childhood seizures, including refractory epilepsy. Despite emerging concerns regarding visual side effects, this drug retains an important role in the medical management of childhood epilepsy. PMID- 11207787 TI - Surgical outcome of corpus callosotomy in patients with drop attacks. AB - PURPOSE: We examined presurgical factors that independently influence surgical outcome after corpus callosotomy. For adequate measurement of the surgical outcome, we analyzed seizure outcome of drop attacks, postoperative overall daily function, and family satisfaction. METHODS: At least 2 years after callosotomy (mean, 40.0 months), we retrospectively investigated 52 patients with drop attacks. As presurgical factors, we analyzed the age at surgery, age at seizure onset, age at drop attack onset, sex, hemiparesis, severe mental retardation, EEG abnormality, MRI abnormality, and extent of callosal section (total or partial callosotomy). Stepwise logistic regression was used for analysis. RESULTS: Satisfactory outcome (seizure cessation or >90% seizure reduction) was achieved in 85% of patients with drop attacks, 32% of those with generalized tonic seizures, and 31% of those with generalized tonic-clonic seizures. The families assessed the overall daily function as improved in 62% of patients, unchanged in 23%, and impaired in 15%. Family satisfaction with callosotomy was achieved in 83% of patients (definitely satisfied, 39%, somewhat satisfied, 44%). Total callosotomy is independently predictive of satisfactory reduction of drop attacks (p = 0.013). A younger age is independently predictive of improvement of overall daily function (impaired and improved: p = 0.004) and family satisfaction (unsatisfied and somewhat satisfied, p = 0.018; unsatisfied and definitely satisfied, p = 0.0006). CONCLUSIONS: In the present study, we found that total callosotomy is more effective for treatment of drop attacks than partial callosotomy and that children receive more benefit than adults after callosotomy. PMID- 11207788 TI - Seizures in multiple sclerosis. AB - PURPOSE: In patients with multiple sclerosis (MS), epileptic seizures occur more frequently than in the general population. The aim of this study was to analyze clinical characteristics of epilepsy in patients with MS, potential correlation between the semiology of seizures, EEG and magnetic resonance imaging (MRI) findings in these patients, as well as to examine the response to anticonvulsant therapy. METHODS: In a series of 268 consecutive patients with definite MS hospitalized at the Institute of Neurology, Belgrade, we identified 20 (7.5%) patients with seizures or epilepsy. All patients with seizures or epilepsy were submitted to standard EEG and brain MRI with gadopentetate dimeglumine. RESULTS: In four patients, epilepsy occurred 1-5 years before other clinical manifestations of MS. Eight patients had seizures only during MS relapses (provoked seizures). In two of them, seizures were the only manifestations of relapse. In 12 patients, seizures occurred regardless of the phase of MS (chronic epilepsy). In the majority of patients, seizures were partial with secondary generalization. Five patients experienced episodes of status epilepticus, and they all had dementia. Abnormal EEG pattern was found in 11 patients. Brain MRI disclosed cortical-subcortical lesions in nine patients and focal cortical atrophy in one, whereas in the remaining patients, findings were inconclusive. Probable EEG-MRI-seizure type correlation existed in 10 patients. CONCLUSIONS: Our data suggest that epilepsy may represent an initial symptom of MS and a single clinical manifestation of a relapse, and further support the assumption of the existing correlation between the presence of cortical-subcortical lesions and epileptic seizures or epilepsy in patients with MS. PMID- 11207789 TI - A detailed analysis of frontal lobe seizure semiology in children younger than 7 years. AB - PURPOSE: We sought to analyze semiology of seizure onset and evolution in young children with frontal lobe epilepsy (FLE), compare this with adult reports, and assess age-related differences. METHODS: We analyzed 111 videotaped seizures from 14 patients with FLE based on focal cortical dysplasia aged 3-81 months (mean, 30 months). Ictal events were categorized into behavioral, consciousness, autonomic, and sensory features, as well as motor patterns, which included tonic, clonic, epileptic spasm, and myoclonic seizure components. We developed a time-scaled datasheet to record each epileptic event as onset, very early, early, or late manifestation. RESULTS: Patients had a high seizure frequency with up to 40 attacks/day; half of them showed a cluster tendency. Forty-seven percent of the seizures started in sleep. Mean duration of seizures was short (29 s). Most common seizure components were motor manifestations, mostly tonic-clonic seizures, and epileptic spasms. Behavioral change was frequent, and hypermotor seizures were not seen. In five patients, the motor features were contralateral to the epileptic focus, including two children with asymmetric epileptic spasms. Secondarily generalized tonic-clonic seizures (SGTCSs) were not recorded, but had been reported in the history of two patients. Complex motor automatisms were not seen, whereas oral automatism appeared in three children. CONCLUSIONS: Motor features are common in young children with FLE, as reported in adults. The characteristics, however, differ. Epileptic spasms and subtle behavioral change were frequent. Hypermotor seizures and complex motor automatisms were not seen, and SGTCSs were unusual. Our results suggest that FLE in young children shows age related features differing from those of adults. PMID- 11207791 TI - Recurrence after a first untreated seizure in the Hong Kong Chinese population. AB - PURPOSE: There is wide variation in the reported prognosis after a first unprovoked generalized tonic-clonic convulsion and in the risk factors that are associated with recurrence. Estimates for the risk of recurrence range from 26 to 71%. We investigated the likelihood of a second attack in Hong Kong Chinese patients. METHODS: One hundred thirty-two patients with a first convulsion that was unexplained by acute neurological or medical causes were retrospectively ascertained. Patients' demographic details, potential risk factors for recurrence, and current seizure status were recorded. Survival analysis was performed using the Kaplan-Meier procedure. RESULTS: The cumulative probability of a second attack at 1, 2, 3, and 4 years was 30, 37, 42, and 47%, respectively. Seizures in patients with abnormal computer tomography scans of the brain were associated with an increased risk of recurrence on multivariate analysis. CONCLUSIONS: Thirty percent of the sample population experienced a second seizure after 1 year. An additional 17% continue to be at risk of a second convulsion during the next 3 years. PMID- 11207790 TI - Changes in public attitudes toward epilepsy in Hungary: results of surveys conducted in 1994 and 2000. AB - Our study investigated public attitudes toward epilepsy, and knowledge and understanding of epilepsy in Hungary. We compared changes of public attitudes in the last six years, hypothesizing a trend of positive changes because of recent national initiatives for acceptance and integration of people with epilepsy (e.g., participation of Hungary in the "Out of the Shadows" world campaign). We also studied how the demographic background of the respondents affects awareness, understanding, and attitudes toward epilepsy. Using a questionnaire design, we conducted a public opinion poll with a representative sample of 1,000 people in 1994 and 6 years later, in 2000. Hungarian respondents were most prejudiced regarding employment of people with epilepsy. In recent years, significant decreases in prejudice rates were found regarding all attitude aspects (marriage, children associating, work). Significant background effects of demographic variables were also apparent: differences by age, education, residence, and family status were found. Some culture-specific characteristics of understanding epilepsy could be observed. Significant positive attitude changes from 1994 to 2000 confirm the need for and potentialities of education of the public and informational initiatives. Demographic influences and culture-specific characteristics could be of relevance in designing public education for different target groups. PMID- 11207792 TI - Reexamination of interictal psychoses based on DSM IV psychosis classification and international epilepsy classification. AB - We sought to examine interictal psychoses based on the international epilepsy classification and DSM IV criteria, with special attention paid to epilepsy types as well as to subcategories of psychoses. One hundred thirty-two outpatients were studied, each with definite evidence of both epilepsy and interictal psychosis clearly demarcated from postictal psychosis. We compared them with 2,773 other epilepsy outpatients as a control. Risk factors for psychosis were examined within the temporal lobe epilepsy (TLE) group and the more extended group of symptomatic localization-related epilepsy. Further, nuclear schizophrenia and other nonschizophrenic psychotic disorders were compared. We confirmed a close correlation between TLE and interictal psychoses. Within the TLE group, only early epilepsy onset and a history of prolonged febrile convulsions were revealed to be significantly associated with interictal psychosis. Within the symptomatic localization-related epilepsy group, such parameters as complex partial seizures, autonomic aura, and temporal EEG foci were closely associated with psychoses. There was also a significant difference between groups as to ictal fear and secondary generalization. Whereas patients with early psychosis onset and a low intelligence quotient were overrepresented in the nuclear schizophrenia group, drug-induced psychosis and alternative psychosis were underrepresented. TLE proved to be preferentially associated with interictal psychoses. Within the TLE group, medial TLE in particular was found to be more closely associated with psychosis. Our data support the original postulation of Landolt, stating that alternative or drug-induced psychoses constitute a definite subgroup of interictal psychoses, which are different from chronic epileptic psychoses that simulate schizophrenia. PMID- 11207793 TI - Impact of pediatric epilepsy on the family: a new scale for clinical and research use. AB - PURPOSE: There is no brief, global instrument available that specifically measures the psychosocial impact of pediatric epilepsy on the family. An 11-item scale was created for parents' use to evaluate the influence of epilepsy on the major aspects of their family and child's life. This will be a helpful tool both in the clinical setting and as an outcome measure for research studies. METHODS: Mothers rated their child's quality of life on a visual analogue scale (1-6) and completed the Impact of Pediatric Epilepsy Scale (IPES), which assesses the impact on academic achievement, participation in activities, health, relationships with family and with peers and siblings, social activities, self esteem, and the caregiver's hopes for their child's future adapted from the scale developed by Jacoby. External validation was determined by comparison of the IPES with physicians' reports of the characteristics of the child's epilepsy and neurological limitations and parents' ratings on the Family Environment Scale or Parenting Stress Index. In addition, each school-aged child completed the Piers Harris Children's Self-Concept Scale, Brother-Sister Questionnaire, and Loneliness Scale. Teachers of children completed the Academic Performance Rating Scale. Seven days later, retest reliability of the IPES was evaluated. RESULTS: Ninety-seven mothers of children aged 2-16 years completed the IPES and the appropriate family and age-related questionnaires. Internal validation on the IPES yielded a Cronbach's a for the scale of 0.92. A significant Pearson's correlation indicated that total scores were consistent over time (r = 0.81). Spearman's correlations for the individual items were also significant, ranging from 0.48 to 0.78. Significant Spearman's correlations also indicated that quality of life was negatively related to impact on each of the 11 items of psychosocial function. Children with IPES scores above the median differed in some psychosocial aspects from those who scored below. Their parents were more stressed, their siblings were more respectful, they had lower self-esteem, and they experienced more emotional problems. Total impact was also significantly related to seizure frequency, total number of medications taken, number of visits to a physician in the previous year, and number of nights spent in hospital for neurological reasons. CONCLUSIONS: The IPES is an accurate, acceptable, and quick measurement tool that reflects the way in which childhood epilepsy has an impact on the child and on family life. It may be helpful in routine clinical care and may be useful in the research setting to find ways to improve the lives of children with epilepsy. PMID- 11207794 TI - Changes in quality of life in epilepsy: how large must they be to be real? AB - PURPOSE: The study goal was to assess the magnitude of change in generic and epilepsy-specific health-related quality-of-life (HRQOL) instruments needed to exclude chance or error at various levels of certainty in patients with medically refractory epilepsy. METHODS: Forty patients with temporal lobe epilepsy and clearly defined criteria of clinical stability received HRQOL measurements twice, 3 months apart, using the Quality of Life in Epilepsy Inventory-89 and -31 (QOLIE 89 and QOLIE-31), Liverpool Impact of Epilepsy, adverse drug events, seizure severity scales, and the Generic Health Utilities Index (HUI-III). Standard error of measurement and test-retest reliability were obtained for all scales and for QOLIE-89 subscales. Using the Reliable Change Index described by Jacobson and Truax, we assessed the magnitude of change required by HRQOL instruments to be 90 and 95% certain that real change has occurred, as opposed to change due to chance or measurement error. RESULTS: Clinical features, point estimates and distribution of HRQOL measures, and test-retest reliability (all > 0.70) were similar to those previously reported. Score changes of +/-13 points in QOLIE-89, +/-15 in QOLIE-31, +/-6.3 in Liverpool seizure severity-ictal, +/-11 in Liverpool adverse drug events, +/-0.25 in HUI-III, and +/-9.5 in impact of epilepsy exclude chance or measurement error with 90% certainty. These correspond, respectively, to 13, 15, 17, 18, 25, and 32% of the potential range of change of each instrument. CONCLUSIONS: Threshold values for real change varied considerably among HRQOL tools but were relatively small for QOLIE-89, QOLIE-31, Liverpool Seizure Severity, and adverse drug events. In some instruments, even relatively large changes cannot rule out chance or measurement error. The relation between the Reliable Change Index and other measures of change and its distinction from measures of minimum clinically important change are discussed. PMID- 11207795 TI - Quantitative assessment of seizure severity for clinical trials: a review of approaches to seizure components. AB - Quantitative assessment of seizure severity has been approached using a variety of systems. This review describes currently available methods and possible new approaches to seizure assessment for clinical trials. A review of the literature on methods of seizure assessments resulted in tabulation of the seizure rating scales known as VA, Chalfont-National Hospital, Liverpool, Hague, and the Occupational Hazard Scale. Seizures have been evaluated by simply counting all events, counting events by type, by clinician ratings, patient ratings, and combinations. Each of the scales has advantages and disadvantages. Most scales share core components: seizure frequency, seizure type, seizure duration, postictal events, postictal duration, automatisms, seizure clusters, known patterns, warnings, tongue biting, incontinence, injuries, and functional impairment. This review revealed a partial consensus about aspects of seizures that are important markers for severity. However, usefulness of the existing scales is limited by lack of data on responsiveness. New approaches are needed to assess changes in seizure severity as a result of an intervention in a clinical trial. PMID- 11207796 TI - Hippocampal volume and glucose metabolism in temporal lobe epileptic foci. AB - PURPOSE: Reports conflict on the relation of glucose metabolism to hippocampal volume in temporal lobe foci. Previous studies usually have used side-side ratios rather than regional metabolic rates. METHODS: We measured hippocampal volume and glucose metabolism in 37 patients with temporal epileptogenic zones identified by ictal video-EEG telemetry. Metabolic rates were normalized to global brain mean. RESULTS: Both 18-fluoro-2-deoxyglucose-PET and volumetric MRI lateralized the epileptic focus determined by ictal video-EEG. There were significant correlations between left-right metabolic asymmetry and hippocampal formation volume left-right ratios. Comparisons between normalized metabolism and hippocampal formation volume, ignoring the side of the epileptic focus, showed significant relations between left hippocampal volume and left inferior lateral temporal metabolism, right hippocampus and right inferior mesial temporal, and left hippocampus and left inferior mesial temporal metabolism. In contrast, when normalized metabolism was compared with hippocampal volume in the epileptic focus, no relation was found. CONCLUSIONS: Our study suggests that the relation between hippocampal volume and glucose metabolism breaks down in epileptic foci and that hypometabolism is not dependent on neuronal loss. It is consistent with data suggesting that hypometabolism is an independent predictor of surgical outcome. PMID- 11207797 TI - Deep wound infection after vagus nerve stimulator implantation: treatment without removal of the device. AB - Effective treatment of deep wound infection without removal of a previously implanted foreign body is difficult. The Neurocybernetic Prosthesis (NCP) System (Cyberonics Inc., Webster, TX, U.S.A.), implanted for vagus nerve stimulation in patients with medically refractory epilepsy, uses coil-like electrodes placed around the left vagus nerve after exposure of the nerve in the carotid sheath. Infection within this compartment endangers the contained structures and makes removal of the system hazardous. We report the case of one patient implanted with the NCP who underwent successful open wound treatment without removal of the system. A 35-year-old man had local signs of wound infection 5 weeks after implantation of a vagus nerve stimulator. Systemic signs of infection were absent. C-reactive protein was slightly elevated, but all other laboratory values were normal. After open wound debridement and thorough rinsing with bacitracin containing solution, the wound was packed with 3% iodoformized gauze. The NCP was left in place. Systemic antibiotic therapy with fosfomycin and cefmenoxim was started. Cultures confirmed an infection with Staphylococcus aureus. The wound was rinsed daily with 3% hydrogen peroxide solution and 5% saline until cultures were sterile and granulation tissue started to fill the wound. Delayed primary closure was performed 2 weeks later. Wound healing was accomplished without removal of the device. No signs of recurrent infection were observed during a follow-up of 1 year. Open wound treatment without removal of the implanted vagus nerve stimulator is feasible in cases of deep cervical wound infection and can be an alternative if removal of the device appears hazardous. PMID- 11207798 TI - The treatment gap in epilepsy: the current situation and ways forward. AB - This article is a summary of a workshop held by the ILAE concerning the issue of the epilepsy treatment gap in developing countries. The gap is defined in terms of those people with epilepsy who are not being appropriately treated and is the result of an array of medical, political, social, economic, and cultural factors. The situation regarding the treatment gap for various countries is reviewed, along with some of its causes. Although the overall gap is estimated to be large, a number of recent projects and interventions have been effective in delivering appropriate treatment to people with epilepsy in underresourced countries of the developing world. It is hoped that these may be transferable elsewhere and that, combined with the ILAE/IBE/WHO Global Campaign against Epilepsy and increased support from the worldwide epilepsy community, the treatment gap will begin to be bridged. PMID- 11207799 TI - Developmental and cellular expression pattern of epithelial sodium channel alpha, beta and gamma subunits in the inner ear of the rat. AB - Endolymphatic ion composition in the adult inner ear is characterized by high K(+) and low Na(+) concentration. This unique ion composition is essential for proper functioning of sensory processing. Although a lot has been learned in recent years about molecules involved in K(+) transport in inner ear, the molecules involved in Na(+) transport are only beginning to emerge. The epithelial Na(+) channel (ENaC) is a highly selective Na(+) channel that is expressed in many Na(+)-reabsorbing tissues. The aim of our study was to investigate whether ENaC is expressed in inner ear of rats and could account for Na(+) reabsorption from endolymph. We detected mRNA for the three channel-forming subunits (alpha, beta and gamma ENaC) in cochlea, vestibular system and endolymphatic sac. mRNA abundance increased during the first 12 days of life in cochlea and vestibular system, coinciding with decreasing Na(+) concentration in endolymph. Expression was strongest in epithelial cells lining scala media, most notably Claudius' cells. As these cells are characterized by a very negative resting potential they would be ideally suited for reabsorption of Na(+). mRNA abundance in endolymphatic sac decreased during the first 6 days of life, suggesting that ENaC might be implicated in reabsorption of endolymph in the endolymphatic sac of neonatal animals. Together, our results suggest that the epithelial Na+ channel is a good candidate for a molecule involved in Na(+) homeostasis in inner ear. PMID- 11207800 TI - The highly sialylated isoform of the neural cell adhesion molecule is required for estradiol-induced morphological synaptic plasticity in the adult arcuate nucleus. AB - The large quantities of polysialic acid (PSA) characterizing highly sialylated isoform of the neural cell adhesion molecule (PSA-NCAM), greatly reduce cell adhesion and render this particular cell surface adhesion molecule a likely candidate to intervene in dynamic neuronal phenomena, such as synaptic plasticity. The hypothalamic arcuate nucleus expresses high levels of PSA-NCAM and maintains a high capacity for neuroplastic changes in the adult. Thus, in the arcuate nucleus of female rats, varying circulating levels of estrogen give rise to a reversible reduction in the number of axo-somatic GABA synapses, together with a changing ensheathing of neuronal somata by astrocytes. To examine the role of PSA in such changes, we perturbed its expression, either by blockade with antibodies raised against this carbohydrate moiety (delivered intracerebroventricularly), or by its enzymatic cleavage after microinjection of endoneuraminidase N over the arcuate nucleus. Either procedure was performed in ovariectomized adult rats that received concurrent treatment with 17 beta estradiol. Morphological synaptic plasticity was analysed using the unbiased disector method to assess synaptic densities in ultrathin sections of the arcuate nucleus immunogold-labelled for GABA. As expected, 17 beta-estradiol induced a significant reduction in the number of GABAergic axo-somatic synapses, a reduction which did not occur after infusion of anti-PSA antibodies or in vivo enzymatic removal of PSA from NCAM. Taken together, our results provide strong evidence that the presence of large quantities of the PSA moiety on NCAM is a necessary prerequisite for estrogen-induced phasic remodelling of synapses in the adult female arcuate nucleus. PMID- 11207801 TI - Progression of spontaneous seizures after status epilepticus is associated with mossy fibre sprouting and extensive bilateral loss of hilar parvalbumin and somatostatin-immunoreactive neurons. AB - The development of spontaneous limbic seizures was investigated in a rat model in which electrical tetanic stimulation of the angular bundle was applied for up to 90 min. This stimulation produced behavioural and electrographic seizures that led to a status epilepticus (SE) in most rats (71%). Long-term EEG monitoring showed that the majority of the rats (67%) that underwent SE, displayed a progressive increase of seizure activity once the first seizure was recorded after a latent period of about 1 week. The other SE rats (33%) did not show this progression of seizure activity. We investigated whether these different patterns of evolution of spontaneous seizures could be related to differences in cellular or structural changes in the hippocampus. This was the case regarding the following changes. (i) Cell loss in the hilar region: in progressive SE rats this was extensive and bilateral whereas in nonprogressive SE rats it was mainly unilateral. (ii) Parvalbumin and somatostatin-immunoreactive neurons: in the hilar region these were almost completely eliminated in progressive SE rats but were still largely present unilaterally in nonprogressive SE rats. (iii) Mossy fibre sprouting: in progressive SE rats, extensive mossy fibre sprouting was prominent in the inner molecular layer. In nonprogressive SE rats, mossy fibre sprouting was also present but less prominent than in progressive SE rats. Although mossy fibre sprouting has been proposed to be a prerequisite for chronic seizure activity in experimental temporal lobe epilepsy, the extent of hilar cell death also appears to be an important factor that differentiates between whether or not seizure progression will occur. PMID- 11207802 TI - Real-time, two-dimensional visualization of ischaemia-induced glutamate release from hippocampal slices. AB - The involvement of excitatory amino acid (EAA) toxicity in ischaemia-induced neuronal cell death has long been suggested. However, in the hippocampus, the brain site most vulnerable to ischaemia, the detailed spatial and temporal patterns of EAA release are not yet known. To address this issue, we have developed a novel strategy for the continuous, real-time, two-dimensional monitoring of EAA release from brain slices. As EAA detector, we used a cell line transformed with the N-methyl-D-aspartate (NMDA) receptor, which is exclusively activated by EAAs, leading to an increase in the intracellular Ca(2+) level. Combined with a calcium imaging technique, the use of this cell line allowed the temporal and regional analysis of EAA release from a brain slice placed directly on top of the clonal cells in a culture dish. Using this strategy, we demonstrated ischaemia-induced EAA release in rat hippocampal slices. Increased EAA release was seen initially in the CA1 region, about 3 min after the beginning of ischaemia, then in the CA3 region and dentate gyrus, and, finally, throughout the hippocampal slice. Regional differences in extracellular EAA levels were also seen, with more EAA being released from the CA1 region than from the middle dentate gyrus. The present results are especially interesting as neurons in the CA1 region are more vulnerable to ischaemia than those in the CA3 region and dentate gyrus. PMID- 11207803 TI - Enhanced CREB phosphorylation in immature dentate gyrus granule cells precedes neurotrophin expression and indicates a specific role of CREB in granule cell differentiation. AB - Differentiation and maturation of dentate gyrus granule cells requires coordinated interactions of numerous processes. These must be regulated by protein factors capable of integrating signals mediated through diverse signalling pathways. Such integrators of inter and intracellular physiological stimuli include the cAMP-response element binding protein (CREB), a leucine zipper class transcription factor that is activated through phosphorylation. Neuronal activity and neurotrophic factors, known to be involved in granule cell differentiation, are major physiologic regulators of CREB function. To examine whether CREB may play a role in governing coordinated gene transcription during granule cell differentiation, we determined the spatial and temporal profiles of phosphorylated (activated) CREB throughout postnatal development in immature rat hippocampus. We demonstrate that CREB activation is confined to discrete, early stages of granule cell differentiation. In addition, CREB phosphorylation occurs prior to expression of the neurotrophins BDNF and NT-3. These data indicate that in a signal transduction cascade connecting CREB and neurotrophins in the process of granule cell maturation, CREB is located upstream of neurotrophins. Importantly, CREB may be a critical component of the machinery regulating the coordinated transcription of genes contributing to the differentiation of granule cells and their integration into the dentate gyrus network. PMID- 11207804 TI - Differential daily expression of Per1 and Per2 mRNA in the suprachiasmatic nucleus of fetal and early postnatal mice. AB - It is well known that there are circadian rhythms of 2-deoxyglucose uptake and neuronal firing in the rat suprachiasmatic nucleus (SCN) during fetal and early postnatal periods. A core clock mechanism in the mouse SCN appears to involve a transcriptional feedback loop in which CLOCK and BMAL1 function as positive regulators and three mPeriod (mPer) genes play a role in negative feedback. Per genes expression occurs not only in the adult SCN but also in the fetal SCN. However, the developmental change in these genes remains unclear. In this experiment, we examined the day--night pattern of expression of Per1 and Per2 mRNA in the mouse SCN and cerebral cortex on embryonic day 17, postnatal day 3, and in young adult mice under a light-dark cycle. Daily rhythms of mRNA content were observed in mPer1 but not mPer2 in the fetal SCN. Interestingly, the expression of mPer2 in the SCN was high throughout the entire day, and a significant daily rhythm of this gene was observed on postnatal day 6. The expression pattern of SCN mPer1 in constant darkness was similar to that seen in the light-dark cycle. The present results suggest that the daily oscillation of mPer1 but not of mPer2 in the SCN in fetal and early postnatal mice may be associated with the daily rhythms of 2-deoxyglucose uptake and neuronal firing. PMID- 11207805 TI - Corticonuclear projections of the cerebellum preserve both anteroposterior and mediolateral pairing patterns. AB - The aim of the present study was to establish whether a diverging arrangement of the corticonuclear cerebellar projections exists and, if so, what relation it has with the inferior olivary complex. Iontophoretic injections of a 1 : 1 mixture of tetramethylrhodamine dextran amine and biotinylated dextran amine into the cerebellar cortex orthogradely labelled fibre terminals in the cerebellar nuclei and retrogradely labelled cell bodies in the inferior olivary complex. The injections were into A, B, C2, C3, D1 and D2 bands. These injections showed diverging projections to the cerebellar nuclei, with 'primary projections' directed to the nuclear region previously reported to be specifically connected with the injected band and 'secondary projections' directed to other nuclear regions. Secondary projections from the A, C2 and C3 bands diverged to nuclear regions primarily controlled by cortical bands lateral to those injected. Secondary projections from the D1, and D2 bands diverged to nuclear regions primarily controlled by cortical bands medial to those injected. Moreover, injections distributed along the D1 and D2 bands showed similar sets of nuclear targets, while those distributed along the A, C2 and C3 bands showed two sets of nuclear targets in relation to the anteroposterior location of the injected area within these bands. The cortical areas that projected to the same set of nuclear targets were innervated from single olivary regions, while those that projected to different sets of nuclear targets were innervated from different subsets of single regions of the inferior olive. The results suggest that the olivary bands of the cerebellar cortex project to the cerebellar nuclei with a diverging pattern that is organized in both the mediolateral and the anteroposterior axes. PMID- 11207806 TI - Mismatch between BDNF mRNA and protein expression in the developing visual cortex: the role of visual experience. AB - Brain-derived neurotrophic factor (BDNF) messenger RNA (mRNA) expression in the rat visual cortex of young and postnatal day 90 (P90) animals is developmentally regulated and influenced by visual experience. In the present paper we compared the expression of BDNF mRNA to the actual changes of BDNF protein occurring during postnatal development and verified whether BDNF protein distribution is controlled by visual activity. To achieve this aim we analysed BDNF mRNA and/or BDNF protein cellular distribution in the rat visual cortex at different postnatal ages by using immunohistochemistry and highly sensitive in situ hybridization. We found that before eye opening (P13), in all cortical layers a large number of visual cortical neurons contain BDNF mRNA with no detectable amount of BDNF protein. At later ages (P23 and P90), the number of BDNF immunostained cells increases; most neurons are double labelled for BDNF mRNA and protein, and a small group of neurons is labelled only for BDNF protein. The cellular increase of BDNF immunolabelling is blocked in animals deprived of visual experience from birth (dark rearing), with a large population of neurons containing BDNF mRNA but not BDNF protein. This is similar to what is observed before eye opening. Exposure of dark-reared rats to a brief period (2 h) of light restores a good match between BDNF mRNA and BDNF protein cellular expression. We propose that visual experience controls the neuronal content of BDNF mRNA and BDNF protein in developing visual cortex. PMID- 11207807 TI - Swelling-activated calcium signalling in cultured mouse primary sensory neurons. AB - The effects of hypo-osmotic membrane stretch on intracellular calcium concentration ([Ca(2+)](i)), cell volume and cellular excitability were investigated in cultured mouse primary sensory trigeminal neurons. Hypotonic solutions (15--45%) led to rapid cell swelling in all neurons. Swelling was accompanied by dose-dependent elevations in [Ca(2+)](i) in a large fraction of neurons. Responses could be classified into three categories. (i) In 57% of the neurons [Ca(2+)](i) responses had a slow rise time and were generally of small amplitude. (ii) In 21% of the neurons, responses had a faster rise and were larger in amplitude. (iii) The remaining cells (22%) did not show [Ca(2+)](i) responses to hypo-osmotic stretch. Slow and fast [Ca(2+)](i) changes were observed in trigeminal neurons of different sizes with variable responses to capsaicin (0.5 microM). The swelling-induced [Ca(2+)](i) responses were not abolished after depletion of intracellular Ca2+ stores with cyclopiazonic acid or preincubation in thapsigargin, but were suppressed in the absence of external Ca(2+). They were strongly attenuated by extracellular nickel and gadolinium. Hypotonic stimulation led to a decrease in input resistance and to membrane potential depolarization. Under voltage-clamp, the [Ca(2+)](i) elevation produced by hypotonic stimulation was accompanied by the development of an inward current and a conductance increase. The time course and amplitude of the [Ca(2+)](i) response to hypo-osmotic stimulation showed a close correlation with electrophysiological properties of the neurons. Fast [Ca(2+)](i) responses were characteristic of trigeminal neurons with short duration action potentials and marked inward rectification. These findings suggest that hypo-osmotic stimulation activates several Ca(2+)-influx pathways, including Gd(3+)-sensitive stretch activated ion channels, in a large fraction of trigeminal ganglion neurons. Opening of voltage-gated Ca(2+) channels also contributes to the response. The pattern and rate of Ca(2+) influx may be correlated with functional subtypes of sensory neurons. PMID- 11207808 TI - In vitro effects of acetyl-DL-leucine (tanganil) on central vestibular neurons and vestibulo-ocular networks of the guinea-pig. AB - For 40 years, the amino acid acetyl-DL-leucine (or isoleucine/Tanganil) has been used in clinical practice to reduce the imbalance and autonomic signs associated with acute vertigo crises. In animal models, acetyl-DL-leucine was shown to accelerate vestibular compensation following unilateral labyrinthectomy, while having only minor effects on normal vestibular function. However, the underlying mechanisms are unknown. In this study, the effect of acetyl-DL-leucine on the activity of central vestibular neurons of the medial vestibular nucleus (MVN) and/or the overall activity of vestibular-related networks was electrophysiologically measured in brainstem slices and in the isolated, in vitro whole brain (IWB) of guinea-pig. Only moderate effects were obtained in normal animals, where both excitatory and inhibitory actions of acetyl-DL-leucine were obtained. However, intracellular recordings from MVN neurons revealed that the nature of the response depended on the resting membrane potential. The neurons excited by acetyl-DL-leucine were significantly hyperpolarized compared to nonsensitive cells, whereas the neurons inhibited by this compound tended to display higher than normal membrane potentials. In accordance with these data, acetyl-DL-leucine reduced the prominent asymmetry characterizing the vestibular related networks of IWBs taken from previously labyrinthectomized animals, by decreasing the activity of the abnormally depolarized neurons on the hyperactive side. Altogether, our results suggest that acetyl-DL-leucine might act mainly on abnormally hyperpolarized and/or depolarized MVN neurons, by bringing back their membrane potential towards a mean value of -65 to -60 mV. Since in animal models, acute vestibular disorders are associated with asymmetrical spontaneous activities of MVN neurons, this study suggests how acetyl-DL-leucine may reduce acute, vestibular-related imbalances in humans. PMID- 11207809 TI - Neural cell adhesion molecule is endocytosed via a clathrin-dependent pathway. AB - Neural cell adhesion molecule (NCAM) constitutes a group of cell surface glycoproteins that regulate cell-cell interactions in the developing and adult brain. Endocytosis is a mechanism which dynamically controls the amount of cell surface NCAM expression and may involve the rapid changes occurring in NCAM expression under certain physiological or pathological conditions. However, the endocytic pathway of NCAM is presently unknown. Using astrocytes in culture and immunofluorescence we show that NCAM is internalized and that the immunolabelling presents a high degree of colocalization with clathrin, alpha-adaptin and transferrin, suggesting that NCAM is endocytosed by a clathrin-dependent pathway. Potassium depletion which disrupts clathrin-mediated endocytosis, inhibited internalization of NCAM. Electron microscopy and immunogold studies also demonstrate that the surface of clathrin-coated vesicles are also immunolabelled for both alpha-adaptin and PSA-NCAM, the highly sialylated isoform of NCAM. Furthermore, immunoprecipation studies demonstrate that NCAM is associated with both clathrin and alpha-adaptin, a component of adaptor complex AP-2, in brain, neurons and astrocytes. These findings indicate that NCAM is mainly endocytosed via clathrin-coated vesicles, suggesting a possible mechanism that may contribute to the rapid changes in NCAM expression at the cell surface. PMID- 11207810 TI - Immunohistochemical localization of voltage-gated calcium channels in substantia nigra dopamine neurons. AB - The rhythmic firing of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) is thought to be mediated by nifedipine-sensitive Ca(2+) channels, although an involvement of omega-conotoxin-sensitive Ca(2+) channels is also suggested. In an attempt to localize such Ca(2+) channels at both the regional and cellular levels, their expression and distribution patterns were immunohistochemically investigated in the rat SNc. The three distinct subtypes of voltage-gated Ca(2+) channels were tested: the class B N-type alpha 1 subunit (CNB1), the class C L-type alpha 1 subunit (CNC1) and the class D L-type alpha 1 subunit (CND1). A large number of SNc neurons showed intense immunoreactivity against CND1 and they were distributed throughout the entire extent. By contrast, many fewer neurons displayed less intense CNC1 immunoreactivity and many of them were located in the lateral aspect of the SNc. No immunoreactivity against CNB1 was detected in the SNc. Moreover, double immunofluorescence analysis in combination with tyrosine hydroxylase staining revealed that virtually all DA neurons were CND1-immunoreactive whereas many DA neurons especially in the medial SNc exhibited only faint or no immunoreactivity against CNC1. Both CNC1 and CND1 were expressed in cell bodies and proximal dendrites of SNc DA neurons, whilst their distal dendrites that penetrated into the substantia nigra pars reticulata expressed CND1 alone. Thus, the ubiquitously and intensely expressed class D alpha 1 subunit of L-type Ca(2+) channels that is sensitive to both nifedipine and omega-conotoxin may be responsible for the pacemaker activity of SNc DA neurons. PMID- 11207811 TI - Characteristics of fast Na(+) current of hypoglossal motoneurons in a rat brainstem slice preparation. AB - Whole-cell patch clamp recordings were performed on hypoglossal motoneurons in a brainstem slice preparation from the neonatal rat brain to study the characteristics of the fast Na(+) current (I(Na)) which has not been hitherto investigated in these cells. To aid voltage clamping of I(Na), cells were bathed in low Na(+) solution, loaded intracellularly with Na(+) (to reverse the Na(+) gradient) or treated with a small dose (20 nM) of tetrodotoxin. In low extracellular Na(+) solution (Na(+) was replaced by choline or N-methyl-D glucamine) I(Na) activated at membrane potentials positive to -45 mV and was half maximally activated at -30 mV. Similar data were obtained when the Na(+) gradient was reversed or tetrodotoxin was applied. I(Na) rapidly activated (1--3.5 ms time constant) and inactivated (1.6 ms time constant at 0 mV) during membrane depolarization. Inactivation was strongly voltage-dependent (half inactivation at -44 mV) and developed mono-exponentially. Recovery from inactivation was bi exponential with fast and slow time constants of 14 and 160 ms, respectively, at 58 mV. The rapid turning on of I(Na) was presumably responsible for the upstroke of the fast action potential generated by these cells while the slow phase of recovery from inactivation might modulate the ability to fire repetitively at high rate. PMID- 11207812 TI - Dopamine D(2) receptors regulate tyrosine hydroxylase activity and phosphorylation at Ser40 in rat striatum. AB - In the striatum, dopamine release is inhibited by activation of dopamine D(2) autoreceptors. Changes in dopamine release have been attributed to changes in the synthesis of dopamine, which is regulated via phosphorylation of tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of catecholamines. Here, we have studied the involvement of dopamine D(2) receptors in the regulation of TH phosphorylation at distinct seryl residues, using phosphorylation site-specific antibodies and a preparation of rat striatal slices. The D(2) receptor agonist, quinpirole, reduced basal TH phosphorylation at Ser40 but not at Ser19 or Ser31. Quinpirole was also able to reduce the increase in Ser40 phosphorylation caused by forskolin, an activator of adenylyl cyclase, without affecting the increase in Ser19 phosphorylation produced by the glutamate receptor agonist, N-methyl-D-aspartate (NMDA). In addition, the dopamine D(2) receptor agonist reduced both basal and forskolin-stimulated activity of TH, measured as 3,4-dihydroxyphenylalanine (DOPA) accumulation. Quinpirole decreased phosphorylation of Ser40 induced by okadaic acid, an inhibitor of protein phosphatase 1 and 2A and Ro-20-1724, a phosphodiesterase inhibitor. In contrast, quinpirole did not affect the increase in Ser40 phosphorylation caused by the cAMP analogue, 8-Br-cAMP. These data indicate that, in the striatum, activation of dopamine D(2) receptors results in selective inhibition of TH phosphorylation at Ser40 via reduction of the activity of adenylyl cyclase. They also provide a molecular mechanism accounting for the ability of dopamine D(2) autoreceptors to inhibit dopamine synthesis and release from nigrostriatal nerve terminals. PMID- 11207813 TI - Gating of vagal inputs by sciatic afferents in nonspinally projecting neurons in the rat rostral ventrolateral medulla oblongata. AB - Integration and coordination of somato-visceral sensory information is crucial to achieve adaptive behavioural responses. We have recently shown that sensory vagal and somato-sensory (sciatic nerve) inputs converge in neurons of the rostral ventrolateral medulla oblongata, which was implicated in adjusting visceral activities to changing somatic performances. In the present study, the neuronal mechanism of interaction between sciatic and vagal sensory inputs was examined in the rostral ventrolateral medulla oblongata using in vivo intracellular recording and labelling. Conditioning stimulation of the contralateral sciatic nerve (2 V) led to a time-dependent inhibition of responses to vagal stimulation (100 microA) in each RVLM neuron that received convergent sciatic and vagal sensory inputs (n = 50). None of these neurons had direct spinal projections, and only 8% of them exhibited a visible response to stimulation of the aortic depressor nerve. A significant attenuation of the amplitude of vagal test responses was present for up to 800 ms of conditioning delay, although the duration of this sciatico-vagal inhibition was greatly dependent on the intensity of both stimuli. The electrophysiological data indicated that sciatico-vagal inhibition is mediated presynaptically, via activation of GABAB receptors. Morphological evidence of axo axonic interactions that may underlie sciatico-vagal inhibition was subsequently found in the electron microscope. It is suggested that during movements of the hindleg, activation of sciatic sensory fibres leads to re-patterning of neuronal activity in RVLM neurons via inhibition of visceral sensory inputs. Sciatico vagal inhibition is likely to affect the activity of those RVLM neurons that modulate higher neuronal activities via ascending projections. PMID- 11207814 TI - The supramammillary nucleus contributes to associative EPSP-spike potentiation in the rat dentate gyrus in vivo. AB - The supramammillary nucleus (SUM) of the hypothalamus sends neural projections to the hippocampus and is supposed to be involved in learning and memory. To test the possibility that SUM afferents modulate hippocampal functions, we investigated the effect of electrical stimulation of the SUM on the induction of long-term potentiation (LTP) at medial perforant path (PP)--granule cell synapses in the dentate gyrus (DG) of anaesthetized rats. High-frequency stimulation of the SUM (100 pulses at 100 Hz) alone did not change PP--DG field potentials. However, when the SUM stimulation was applied simultaneously with weak tetanic stimulation of the PP (20 pulses at 20 Hz) which alone did not induce any potentiation, it produced a long-lasting potentiation of the population spike, without an accompanying increase in the population excitatory postsynaptic potential (EPSP). The EPSP-spike (E-S) potentiation induced by pairing SUM and PP stimulation was abolished by lesions of the fimbria--fornix, a major pathway of SUM afferents. SUM stimulation applied 1 s before or after PP stimulation failed to produce E-S potentiation, and SUM stimulation augmented PP--DG field potentials during tetanic stimulation. Furthermore, the E-S potentiation was abolished by blocking GABAergic neurotransmission with picrotoxin. These results suggest that coactivation of SUM and PP inputs produces a long-lasting increase of granule cell excitability by modulating GABAergic inhibition. SUM afferents may contribute to associative memory processing by modulating hippocampal excitability. PMID- 11207815 TI - RGS9 proteins facilitate acute tolerance to mu-opioid effects. AB - This paper reports that regulators of G-protein signalling (RGS) proteins modulate the timing and amplitude of opioid signals by a push-pull mechanism. This is achieved without noticeable changes in the binding properties of opioids, e.g. beta-endorphin to mu-opioid receptors. The expression of RGS proteins was reduced by blocking their mRNA with antisense oligodeoxynucleotides (ODN). Knock down of RGS2 or RGS3 diminished morphine and beta-endorphin analgesia, whereas that of RGS9 or RGS12 enhanced this activity. In mice with impaired RGS9, but not impaired RGS2, the potency and, in particular, the duration of opioid antinociception increased. Further, the animals did not exhibit acute tolerance generated by a single and efficacious dose of morphine, nor did they develop tolerance after a daily i.c.v. injection of the opioid for 4 days. In a model of sustained morphine treatment, the impairment of RGS9 proteins facilitated increases in the response to the delivered opioid. This was only effective for 2- 3 h after the subcutaneous implantation of an oily morphine pellet; later, tolerance developed. To reduce the impact of the chronic morphine acting on opioid receptors, other RGS proteins presumably substitute the GTPase-activating function of RGS9 on morphine-activated G-alpha-GTP subunits. The desensitization of mu-opioid receptors appears to be a cell membrane-limited process facilitated by RGS9's sequestering of agonist-segregated G alpha subunits. PMID- 11207816 TI - Influence of glucocorticoids on dopaminergic transmission in the rat dorsolateral striatum. AB - Glucocorticoid hormones exert strong influences on central neurotransmitter systems. In the present work, we examined the functional consequences of corticosterone suppression on the dopaminergic transmission in the dorsolateral striatum by studying the expression of Fos-like proteins and extracellular dopamine levels. Glucocorticoid hormones were suppressed by adrenalectomy, and the specificity of the effects assessed by restoring physiological plasmatic corticosterone concentrations. We show that, in the dorsolateral striatum, glucocorticoids modify postsynaptic dopaminergic transmission. Suppression of glucocorticoids decreased the induction of Fos proteins in response to a direct agonist of dopamine D(1) receptors (SKF 82958, 1.5 mg/kg, i.p.), but not the release of dopamine induced by morphine (2 mg/kg, s.c.) or the density of the limiting enzyme of dopamine synthesis, tyrosine hydroxylase. In contrast to the dopaminergic response to morphine, the response to cocaine (15 mg/kg, i.p.) was modified by the suppression of corticosterone. In this case, adrenalectomy increased cocaine-induced changes in extracellular dopamine but did not modify the expression of Fos-like proteins. This absence of changes in cocaine-induced Fos-like proteins might result from a compensatory mechanism between the increase in the dopaminergic response and the decrease in the functional activity of dopamine D(1) receptors. The increased dopaminergic response to cocaine also contrasts with the decreased response previously observed in the shell of the nucleus accumbens [Barrot et al. (2000) Eur. J. Neurosci., 12, 973-979]. The present data highlight the profound heterogeneous influence of glucocorticoids within dopaminergic projections. PMID- 11207817 TI - Novelty-evoked elevations of nucleus accumbens dopamine: dependence on impulse flow from the ventral subiculum and glutamatergic neurotransmission in the ventral tegmental area. AB - In vivo microdialysis in freely moving rats was used to monitor novelty-evoked elevations in extracellular dopamine in the nucleus accumbens septi (NAS) and to examine the role of the ventral subiculum of the hippocampus and glutamatergic transmission in the ventral tegmental area (VTA) on these elevations. Exposure to novel stimuli evoked investigatory activity and increased nucleus accumbens dopamine. Unilateral injections of the sodium channel blocker tetrodotoxin (0.16 ng/0.5 microL) into the ventral subiculum ipsilateral to the dialysed NAS abolished novelty-evoked elevations in dopamine. Injections of tetrodotoxin into the contralateral VS did not prevent novelty-evoked elevations in nucleus accumbens dopamine. Unilateral perfusion (via microdialysis) of the ionotropic glutamate receptor antagonists kynurenic acid (1 mM) into the ipsilateral but not the contralateral VTA blocked novelty-evoked elevations in nucleus accumbens dopamine. Neither unilateral injections of tetrodotoxin nor unilateral perfusion of kynurenic acid disrupted investigatory behaviour. These data indicate that phasic elevations in nucleus accumbens dopamine evoked by exposure to unconditioned novel stimuli are dependent on impulse flow from the hippocampus and glutamatergic transmission in the VTA. PMID- 11207818 TI - Immunocytochemical identification and analysis of the diffuse bipolar cell type DB6 in macaque monkey retina. AB - The distribution and morphology of CD15-immunoreactive bipolar cells were studied in the retina of macaque monkey. Labelled cells have a large dendritic tree contacting several cones and a narrowly stratified axon terminal that ends deep in the inner plexiform layer, close to the ganglion cell layer. The morphology of the labelled cells corresponds to that of the diffuse bipolar cell type named DB6 by Boycott & Wassle (1991; Eur. J. Neurosci., 3,1069). We conclude that CD15 is a marker for DB6 bipolar cells, enabling the quantitative analysis of the distribution and connectivity of this diffuse bipolar cell type. PMID- 11207819 TI - Bcl-2 overexpression per se does not promote regeneration of neonatal crushed optic fibers. AB - We have explored whether overexpression of the bcl-2 gene 'per se' can promote regeneration of retinal ganglion cells (RGCs) after optic nerve axotomy in developing transgenic mice. We have used newborn mice (postnatal day 5) because at this age the central nervous system environment is more permissive for regeneration than in adults, thus, maximizing the probability to detect a regeneration-promoting role of bcl-2. Thirty days postsurgery we found that in mice overexpressing bcl-2, a high proportion of retinal ganglion cells survived and also that some fibers in the proximal stump of the optic nerve were preserved. However, the optic nerve of transgenic mice does not show signs of regeneration. On the contrary, in the presence of Schwann cell transplants, there are signs of fiber regrowth. Indeed, many axonal terminals cross the crush site and reach the chiasm in both wild type and transgenic mice nerves. These results suggest that bcl-2 overexpression is not sufficient 'per se' to increase the regenerative potentiality of axotomized RGCs. PMID- 11207821 TI - Precursor lesions of ovarian epithelial malignancy. AB - Most ovarian carcinomas arise from the mesothelial surface lining of the ovaries, or from invaginations of this lining into the superficial ovarian cortex to form cortical inclusion cysts. The native ovarian surface mesothelium is of an 'uncommitted' phenotype, and has potential to modulate to epithelial or mesenchymal phenotypes in response to signals such as those associated with ovulation. The exposure of the mesothelial lining of an inclusion cyst to the ovarian stromal microenvironment may be responsible for the phenotypic change to Mullerian epithelium so commonly seen in these cysts. Mullerian metaplasia is usually to a serous phenotype, and it is possible that undefined molecular events occurring in an inclusion cyst that has undergone Mullerian metaplasia may initiate neoplastic change in these cysts. This may be the developmental pathway of most invasive serous carcinomas. Occasional rare cases of ovarian intraepithelial neoplasia, manifested by epithelial atypia in an inclusion cyst or on the surface epithelium without invasive carcinoma, are identified histologically. Serous borderline tumours represent a separate category and in most cases probably do not progress to frank carcinoma. Mucinous carcinomas may in some cases have arisen from pre-existing benign and borderline mucinous tumours. Endometriosis of the ovary is associated with genetic abnormalities and is frequently found in association with clear cell and endometrioid carcinomas, suggesting that in many cases these latter two types of carcinoma may have arisen directly from endometriotic deposits. Ovaries removed prophylactically from women with a family history of ovarian carcinoma or with a mutation in one of the genes predisposing to ovarian carcinoma should be processed in their entirety, and examined closely not just for obviously neoplastic lesions, but also for more subtle morphological abnormalities of the surface epithelium or the epithelium lining cortical inclusion cysts. PMID- 11207820 TI - Vasoactive intestinal polypeptide (VIP) phase-shifts the rat suprachiasmatic nucleus clock in vitro. AB - In mammals, the principal circadian pacemaker is housed in the hypothalamic suprachiasmatic nuclei (SCN). The SCN exhibit high levels of vasoactive intestinal polypeptide (VIP) immunoreactivity and two of the three VIP receptors, VPAC(2) and PAC(1), are found in the rat SCN. However, the role of VIP in the SCN remains unclear. In this study, we examined the phase-resetting actions of VIP and selective VIP receptor agonists on the electrical activity rhythm of rat SCN neurons in vitro. Application of VIP during the subjective day did not shift the peak in the firing rate rhythm. However, VIP treatment during the early or late subjective night evoked a small phase delay or a large phase advance, respectively. The phase-advancing effect of VIP was reproduced by the novel VPAC(2) receptor agonist RO 25-1553, but not by pituitary adenylate cyclase activating peptide (a potent PAC(1) receptor agonist), or by [K15,R16,L27]VIP(1 7)/GRF(8-27), a novel, selective VPAC(1) receptor agonist. These data show that VIP phase-dependently phase-resets the rodent SCN pacemaker in vitro, presumably via the VPAC(2) receptor. As the pattern of phase-shifting evoked by VIP and RO 25-1553 resembles the phase-resetting actions of light on rodent behavioural rhythms, these data support a role for VIP and the VPAC(2) receptor in photic entrainment of the rodent circadian pacemaker. PMID- 11207822 TI - Overexpression of HER2/neu in solid tumours: an immunohistochemical survey. AB - AIMS: Using a standardized immunohistochemical assay we have evaluated 575 primary neoplasms of different histogenesis to determine the incidence of HER2 overexpression in some of the most common categories of human solid neoplasms. This study addresses the variable incidence of HER2 overexpression previously published for some tumour types. METHODS AND RESULTS: The immunohistochemical staining was performed on paraffin sections of surgical specimens and a well defined scoring system based upon numbers of HER2 receptors expressed on the cell surface was applied. Overexpression of HER2 as defined as a HER2 score of equal or greater than 2 was seen in breast cancer (22%), pulmonary adenocarcinoma (28%), colorectal adenocarcinomas (17%), pulmonary squamous (11%) and gastric adenocarcinomas (11%). As expected, the proportion of cases with a HER2 score of 3 was highest in breast cancer. Contrary to published results prostate and pancreas adenocarcinomas showed a very low incidence of HER2 overexpression. CONCLUSIONS: Overexpression of HER2 is detected immunohistochemically in a proportion of epithelial neoplasms of diverse histogenesis in addition to ductal breast cancer. The standardized format of the assay will allow comparative analyses of studies performed at different institutions. PMID- 11207823 TI - Inflammatory pseudotumour (inflammatory myofibroblastic tumour) of the pancreas: a report of six cases associated with obliterative phlebitis. AB - AIMS: To describe in detail an uncommon pancreatic condition, which generally presents with cholestasis and a mass lesion suspicious of malignancy, and which is characterized histologically by proliferation of fibrous tissue with associated moderate or marked inflammation, as well as obliterative phlebitis. METHODS AND RESULTS: Out of a consecutive series of 23 pancreaticoduodenectomy specimens which on histological evaluation were found to contain no malignant tumour, six cases characterized by the features mentioned above were identified and investigated further. Poor circumscription, firm consistence, histology of dense sclerosis with scattered round cell infiltrates and associated obliterative phlebitis and often perineural accentuation of inflammation were the distinguishing features. On the basis of available histological evidence, the term inflammatory pseudotumour perhaps remains the term best suited to designate this entity, since it sums up its two most distinctive features. However, the possibility that this lesion is in fact a neoplastic process with reactive inflammation (inflammatory myofibroblastic tumour) cannot be ruled out on the basis of the histology, and remains a serious consideration in view of the proven neoplastic nature of lesions with very similar histology arising elsewhere in the body. Importantly, none of the pancreatic lesions reported here recurred or progressed (five informative cases, median follow-up time 70 months). CONCLUSIONS: Inflammatory pseudotumour (inflammatory myofibroblastic tumour) of the pancreas may closely mimic pancreatic adenocarcinoma clinically and radiologically. PMID- 11207824 TI - Interrelationship between Epstein-Barr virus infection in gastric carcinomas and the expression of apoptosis-associated proteins. AB - AIMS: Epstein-Barr virus (EBV) and its associated proteins may be protective against the occurrence of apoptosis that would normally inhibit cancer development and progression. Alternatively, the viral infection may cause altered or mutated expression of oncogenes or tumour suppressor genes that are necessary for tumour development, an action that may also involve apoptosis. In this study, a relationship was sought between occurrence of EBV infection, expression of apoptosis-associated proteins (tumour suppressor gene p53 and oncogenes c-myc and bcl-2) and levels of cell death (apoptosis or necrosis) in 119 cases of gastric carcinoma. METHODS AND RESULTS: The EBV status of the gastric carcinomas (using the EBV-encoded small RNA I (EBER-1) and in-situ hybridization), stage and grade of tumour and sex of patients were compared for bcl-2, p53 and c-myc expression patterns. EBER-1 was detected in approximately 20% of cases studied. There was no significant correlation between levels of cell death in the tumour tissue and EBV status. In the protein analyses, development and progression of gastric carcinoma, with or without EBV infection, was independent of bcl-2 expression. However, in gastric cancers with EBV infection, p53 overexpression was inhibited and c-myc expression was increased in early stage cancers, in comparison with decreased c-myc expression in late stage cancers. CONCLUSIONS: The p53 and c-myc expression patterns indicate that EBV-infected gastric carcinomas are less likely to have a natural regression via apoptosis at an early stage and explain, in part, the resistance to treatment of late stage of gastric cancers. PMID- 11207826 TI - S100 expression in cutaneous scars: a potential diagnostic pitfall in the diagnosis of desmoplastic melanoma. AB - AIMS: The histological distinction of desmoplastic melanoma from cutaneous scar tissue, particularly in the context of re-excision specimens or possible recurrence, may be very difficult. Immunostaining for S100 protein is often used to discriminate although there are little data on S100 expression in scar tissue. The aim of this study was to assess whether S100-positive cells are present in dermal scars and, if so, their extent, distribution and nature. METHODS AND RESULTS: Twenty-two re-excision specimens of previously biopsied nonmelanocytic skin lesions were reviewed. Formalin-fixed paraffin-embedded sections containing dermal scars were stained by a standard ABC immunoperoxidase technique for S100 protein, CD1a and neurofilaments. The distribution and morphology of positive cells within the dermal scar tissue were documented. Cells expressing S100 protein were identified within the scars of 21 of the 22 cases. The number of S100-positive cells varied between cases but in four specimens was substantial. They displayed a variety of morphological appearances but the majority were spindle-shaped. A few showed mild cytological atypia. It is suggested that the majority represent Schwann cells with a minority of Langerhans cells and cells of uncertain lineage. CONCLUSION: S100-positive cells, including spindle cells showing mild atypia, are found in cutaneous scars. S100 staining of re-excision specimens or putative recurrences of desmoplastic melanoma should be interpreted with caution. PMID- 11207825 TI - Evidence that neurones accumulating amyloid can undergo lysis to form amyloid plaques in Alzheimer's disease. AB - AIMS: Amyloid has recently been shown to accumulate intracellularly in the brains of patients with Alzheimer's disease (AD), yet amyloid plaques are generally thought to arise from gradual extracellular amyloid deposition. We have investigated the possibility of a link between these two apparently conflicting observations. METHODS AND RESULTS: Immunohistochemistry and digital image analysis was used to examine the detailed localization of beta-amyloid(42) (A beta 42), a major component of amyloid plaques, in the entorhinal cortex and hippocampus of AD brains. A beta 42 first selectively accumulates in the perikaryon of pyramidal cells as discrete, granules that appear to be cathepsin D positive, suggesting that they may represent lysosomes or lysosome-derived structures. AD brain regions abundantly populated with pyramidal neurones exhibiting excessive A beta 42 accumulations also contained evidence of neuronal lysis. Lysis of these A beta 42-burdened neurones apparently resulted in a local, radial dispersion of their cytoplasmic contents, including A beta 42 and lysosomal enzymes, into the surrounding extracellular space. A nuclear remnant was found at the dense core of many amyloid plaques, strengthening the idea that each amyloid plaque represents the end product of a single neuronal cell lysis. The inverse relationship between the amyloid plaque density and pyramidal cell density in the AD brain regions also supports this possibility, as does the close correlation between plaque size and the size of local pyramidal cells. CONCLUSIONS: Our findings suggest that excessive intracellular accumulation of A beta 42-positive material in pyramidal cells can result in cell lysis, and that cell lysis is an important source of amyloid plaques and neuronal loss in AD brains. PMID- 11207827 TI - Calcifying/ossifying synovial sarcoma shows t(X;18) with SSX2 involvement and mitochondrial calcifications. AB - AIMS: Synovial sarcoma with extensive calcification and ossification is a rare variant, the ultrastructural, cytogenetic and molecular analysis of which has not been reported previously. METHODS AND RESULTS: A large mass in the shoulder of a 20-year-old male patient led to a deformity of the chest wall, thus supporting the hypothesis that this is a slowly growing variant of synovial sarcoma. Nevertheless, the patient developed metastatic lung disease 7 months after resection. On histology, the monophasic spindle cell proliferation was in several areas obscured by the massive calcification and ossification. Immunohistochemistry showed keratin, epithelial membrane antigen, vimentin and CD99 expression. The cytogenetic analysis revealed a single t(X;18)(p11.2; q11.2), typical for synovial sarcoma. Additional fluorescence in-situ hybridization revealed SSX2 involvement. At the ultrastructural level, prominent needle-shaped intramitochondrial crystals were present, both in the cytoplasm and in the extracellular matrix. CONCLUSION: The presence of the t(X;18) with SSX2 involvement definitively characterizes this tumour as a variant of synovial sarcoma. In addition, the needle-like mitochondrial calcifications give a possible clue to the pathogenesis of the extensive metaplastic ossification and calcification. PMID- 11207828 TI - Lymphoproliferative disorders in children with primary immunodeficiencies: immunological status may be more predictive of the outcome than other criteria. AB - AIMS: Lymphoproliferative disorders (LPDs) are a severe complication in primary immunodeficiency and post-transplant patients. In primary immunodeficiency patients, LPDs are not well-known and, thus, we tried to evaluate their distinctive features and to determine prognostic factors predictive of clinical outcome by comparison with LPDs in post-transplant children. METHODS AND RESULTS: Clinical records and histopathology of 18 LPDs occurring in primary immunodeficieny children were compared with those of 10 LPDs in post-transplant children, together with results of in-situ hybridization for the detection of Epstein-Barr virus (EBV)-RNA and molecular biological techniques. LPDs were frequently extranodal, EBV-associated, and were more commonly pleomorphic in primary immunodeficiency than in post-transplant patients. A low T-cell count and abnormal T-cell function indicated bad prognosis in both groups. Polymorphic LPDs (PLPDs) were most frequent (n = 19), whereas lymphomas were rare (n = 7), and pseudo-tumoral lymphoid hyperplasias (n = 2) were observed only in primary immunodeficiency. Comparative p53/bcl-2 staining revealed a p53 overexpression in lymphomas compared with PLPDs; CD20/CD79a showed a similar staining in lymphomas, whereas PLPD expressed mainly CD20. TCR and IgH rearrangements did not help in distinguishing PLPDs from lymphomas, but detection of IgH clonality by Southern blot indicated poor prognosis, whereas oligoclonality by Southern blot regardless of PCR clonality and especially a polyclonal profile by Southern blot and PCR indicated a relatively good prognosis. CONCLUSIONS: This study documents the pleomorphism of LPDs in primary immunodeficiency compared to post-transplant children, even if some LPDs are similar in both groups (PLPDs). No criteria are useful enough to ascertain the diagnosis of malignancy in this series. Some molecular biological criteria help to predict the clinical outcome which, nevertheless, seems to depend more on the degree of immunosuppression and on T lymphocyte presence and function. PMID- 11207829 TI - Increased proliferation activities of vascular endothelial cells and tumour cells in residual hepatocellular carcinoma following transcatheter arterial embolization. AB - AIMS: Transcatheter arterial embolization induces extensive ischaemic necrosis or hypoxia via the obstruction of the hepatic artery in hepatocellular carcinoma (HCC). Ischaemia is strongly correlated with an increased expression of angiogenic factor and stimulates an increase in angiogenesis, including endothelial cell proliferation. The aim of this study was to evaluate whether ischaemic necrosis induced by transcatheter arterial embolization could increase the proliferative activities of intratumoral endothelial cells or tumour cells in the residual HCC. METHODS AND RESULTS: Using a double immunohistochemical technique (Ki67 antibody to determine the proliferative activity and CD34 antibody to highlight the intratumoral endothelial cells), we performed immunohistochemical staining for 24 HCCs treated by transcatheter arterial embolization. Seven HCCs without any preoperative transcatheter arterial embolization and nine cirrhosis cases were also studied as the control cases. The residual tumour was then divided into five areas at 0.5 mm intervals, according to the distance from the necrotic margin induced by embolization. The Ki67 labelling indices of the intratumoral endothelial cells and tumour cells were counted in each area. The correlation between the indices and the corresponding distance from the ischaemic necrosis was analysed. The Ki67 labelling index of intratumoral vascular endothelial cells in the area less than 0.5 mm from the necrotic margin (area 1) was 10.60 +/- 3.64% (mean +/- SD), which was twofold greater than those of the other areas more than 0.5 mm from the margin (areas 2- 5) and those of the control HCCs without preoperative transcatheter arterial embolization. In addition, the proliferation labelling index of the tumour cells was 35.77 +/- 11.45% (mean +/- SD) in area 1. This was higher than those of areas 2--5 and control HCCs without preoperative transcatheter arterial embolization. There was a positive correlation between the proliferation of both endothelial and tumour cells and ischaemic necrosis (P < 0.05). CONCLUSIONS: Our study suggests that the proliferative activity of intratumoral endothelial cells and tumour cells is increased by ischaemic necrosis induced by transcatheter arterial embolization, and its effect is maximal in the area adjacent to the necrosis (less than 0.5 mm from the necrotic margin). PMID- 11207830 TI - Limitations of the histopathological diagnosis and prognostic assessment of hepatocellular carcinoma. PMID- 11207832 TI - Endometrial cancer, vasculitis of the genital tract and occult temporal arteritis. PMID- 11207835 TI - JAGS Enters the New Millennium: Direction, Decision, Determination, Dedication, and Distinction. PMID- 11207834 TI - Highlights of Papers in Clinical Investigation Section. PMID- 11207836 TI - The effect of aging on circulating levels of proinflammatory cytokines during septic shock. Norasept II Study Investigators. AB - BACKGROUND: As the proportion of the population that is older continues to rise, infection in older people has become an important healthcare problem. Although aging is associated with multiple abnormalities in immune function, the effect of aging on the production of proinflammatory cytokines has not been well studied under conditions of clinical stress. OBJECTIVES: The aim of this study was to examine the effect of aging on circulating levels of the proinflammatory cytokines in a large cohort of septic shock patients. We hypothesized that aging would be associated with a diminished proinflammatory cytokine response to sepsis. DESIGN: Patients with septic shock who were enrolled in the placebo limb of the North American Sepsis Trial (NORASEPT II) study were analyzed. SETTING: The intensive care units of 105 hospitals in the United States and Canada. PARTICIPANTS: Nine hundred and thirty patients presenting to hospital within 12 hours of the onset of septic shock. MEASUREMENTS: Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble tumor necrosis factor-receptor-55 (sTNF-R55), and soluble tumor necrosis factor-receptor-75 (sTNF-R75) concentrations were measured at enrollment. The study population was broken down into five age groups as follows: less than 50 years (group one), 50 to 64 years (group two), 65 to 74 years (group three), 75 to 84 years (group four), and 85 or older (group five). Clinical, demographic, and cytokine data were extracted to describe each age group. RESULTS: Data were available for 930 patients. The patients' mean age (+/- SD) was 59 +/- 17 years (range, 18 to 102). There were 280 patients in group one, 242 in group two, 210 in group three, 150 in group four, and 48 in group five. The primary diagnoses; clinical characteristics; and IL-6, sTNF-R55, and sTNF-R75 levels were similar among the five age groups. The TNF-alpha levels were significantly higher, however, in the oldest group of patients (group five). The 28-day survival was 49% in patients over the age of 75 and 58% in those under 75 years (P = .03). There was no gender difference in survival or cytokine levels. CONCLUSIONS: Contrary to our expectations, we found that aging was not associated with a decline in the circulating levels of proinflammatory cytokines. PMID- 11207837 TI - Exercise training for rehabilitation and secondary prevention of falls in geriatric patients with a history of injurious falls. AB - OBJECTIVE: To determine the safety and efficacy of an exercise protocol designed to improve strength, mobility, and balance and to reduce subsequent falls in geriatric patients with a history of injurious falls. DESIGN: A randomized controlled 3-month intervention trial, with an additional 3-month follow-up. SETTING: Out-patient geriatric rehabilitation unit. PARTICIPANTS: Fifty-seven female geriatric patients (mean age 82 +/- 4.8 years; range 75-90) admitted to acute care or inpatient rehabilitation with a history of recurrent or injurious falls including patients with acute fall-related fracture. INTERVENTION: Ambulatory training of strength, functional performance, and balance 3 times per week for 3 months. Patients of the control group attended a placebo group 3 times a week for 3 months. Both groups received an identical physiotherapeutic treatment 2 times a week, in which strengthening and balance training were excluded. MEASUREMENTS: Strength, functional ability, motor function, psychological parameters, and fall rates were assessed by standardized protocols at the beginning (T1) and the end (T2) of intervention. Patients were followed up for 3 months after the intervention (T3). RESULTS: No training-related medical problems occurred in the study group. Forty-five patients (79%) completed all assessments after the intervention and follow-up period. Adherence was excellent in both groups (intervention 85.4 +/- 27.8% vs control 84.2 +/- 29.3%). The patients in the intervention group increased strength, functional motor performance, and balance significantly. Fall-related behavioral and emotional restrictions were reduced significantly. Improvements persisted during the 3 month follow-up with only moderate losses. For patients of the control group, no change in strength, functional performance, or emotional status could be documented during intervention and follow-up. Fall incidence was reduced nonsignificantly by 25% in the intervention group compared with the control group (RR:0.753 CI:0.455-1.245). CONCLUSIONS: Progressive resistance training and progressive functional training are safe and effective methods of increasing strength and functional performance and reducing fall-related behavioral and emotional restrictions during ambulant rehabilitation in frail, high-risk geriatric patients with a history of injurious falls. PMID- 11207838 TI - Coimpairments as predictors of severe walking disability in older women. AB - OBJECTIVE: Severe disabilities are common among older people who have impairments in a range of physiologic systems. It is not known, however, whether the presence of multiple impairments, or coimpairments, is associated with increased risk of developing new disability. The aim of this study was to determine the combined effects of two impairments, decreased knee-extension strength and poor standing balance, on the risk of developing severe walking disability among older, moderately-to-severely disabled women who did not have severe walking disability at baseline. DESIGN: The Women's Health and Aging Study is a 3-year prospective study with 6 semi-annual follow-up data-collection rounds following the baseline. SETTING: At baseline, knee-extension strength and standing balance tests took place in the participants' homes. PARTICIPANTS: 758 women who were not severely walking disabled at baseline. MEASUREMENTS: Severe walking disability was defined as customary walking speed of < 0.4 meters/second and inability to walk one quarter of a mile, or being unable to walk. RESULTS: Over the course of the study, 173 women became severely disabled in walking. The cumulative incidence of severe walking disability from the first to the sixth follow-up was: 7.8%, 12.0%, 15.1% 19.5% 21.2%, and 22.8%. In Cox proportional hazards models, both strength and balance were significant predictors of new walking disability. In the best balance category, the rates of developing severe walking disability expressed per 100 person years were 3.1, 6.1, and 5.3 in the highest- to lowest-strength tertiles. In the middle balance category, the rates were 9.6, 13.2, and 14.7, and in the poorest balance category 21.6, 12.7, and 37.1, correspondingly. The relative risk (RR) of onset of severe walking disability adjusted for age, height, weight, and race was more than five times greater in the group with poorest balance and strength (RR 5.12, 95% confidence limit [95% CI] 2.68-9.80) compared with the group with best balance and strength (the reference group). Among those who had poorest balance and best strength, the RR of severe walking disability was 3.08 (95% CI 1.33-7.14). Among those with best balance and poorest strength, the RR was 0.97 (95% CI 0.49-1.93), as compared with the reference group. CONCLUSION: The presence of coimpairments is a powerful predictor of new, severe walking disability, an underlying cause of dependence in older people. Substantial reduction in the risk of walking disability could be achieved even if interventions were successful in correcting only one of the impairments because a deficit in only one physiologic system may be compensated for by good capacity in another system. PMID- 11207839 TI - Simultaneous validation of ten physical activity questionnaires in older men: a doubly labeled water study. AB - OBJECTIVE: The purpose of this study was to simultaneously validate 10 physical activity (PA) questionnaires in a homogenous population of healthy elderly men against the reference method: doubly labeled water (DLW). DESIGN: Cross-sectional study. SETTING: Community-based sample from Lyon, France. PARTICIPANTS: Nineteen healthy old men (age 73.4 +/- 4.1 years), recruited from various associations for elderly people in Lyon, agreed to participate in the study. MEASUREMENTS: The questionnaire-derived measures (scores) were compared with two validation measures: DLW and maximal oxygen uptake (VO2max). With the DLW method three parameters were calculated: (1) total energy expenditure (TEE), (2) physical activity level (PAL), i.e., the ratio of TEE to resting metabolic rate, (3) energy expenditure of PA. RESULTS: Relative validity. Correlation between the questionnaires and TEE ranged from 0.11 for the Yale Physical Activity Survey (YPAS) total index to 0.63 for the Stanford usual activity questionnaire. This questionnaire also gave the best correlation coefficients with PAL (0.75), and with VO2max (0.62). Significant results with TEE measured by the DLW method were also obtained for college alumni sports score, Seven Day Recall moderate activity, and Questionnaire d'Activite Physique Saint-Etienne sports activity (r = 0.54, r = 0.52, and r = 0.54, respectively). Absolute validity. No difference was found between PA measured by the Seven Day Recall or by the YPAS and DLW, on a group basis. The limits of agreement were wide for all the questionnaires. CONCLUSIONS: Only a few questionnaires demonstrated a reasonable degree of reliability and could be used to rank healthy older men according to PA. Correlation coefficients were best when the Stanford Usual Activity Questionnaire was compared with all the validation measures. The two questionnaires reporting recent PA, the Seven Day Recall, and YPAS accurately assessed energy expenditure for the group. The individual variability was high for all the questionnaires, suggesting that their use as a proxy measure of individual energy expenditure may be limited. PMID- 11207840 TI - Patterns of self-rated health in older adults before and after sentinel health events. AB - OBJECTIVES: To describe and compare patterns of change in self-rated health for older adults before death and before and after stroke, myocardial infarction, congestive heart failure, cardiac procedure, hospital admission for cancer, and hip fracture. DESIGN: "Event cohort," measuring time in months before and after the event. SETTING: Four U.S. communities. PARTICIPANTS: 5888 participants in the Cardiovascular Health Study (CHS), sampled from Medicare rolls and followed up to 8 years. Mean age at baseline was 73. MEASUREMENTS: Self-rated health, including a category for death, assessed at 6-month intervals, and ascertainment of events. METHODS: We examined the percentage that was healthy each month in the 5 years before death and in the 2 years before and after the other events, and compared the patterns to a "no event" group and to one another, using graphs and linear regression. RESULTS: For people who died, health status declined slowly until about 9 months before death, when it dropped steeply. Comparing persons equally far from death, health was unrelated to age, but men and whites were healthier than women and blacks. Health for other events declined before the event, dropped steeply at the event, showed some recovery, and then declined further after the event. About 65% to 80% of the subjects were healthy 2 years before their event, but only 35% to 65% were healthy two years afterwards. Patterns were similar although less extreme for the "no event" group. CONCLUSION: Visualizing trajectories of health helps us understand how serious health events changes health. Conclusions about change must be drawn with care because of a variety of possible biases. We have described the trajectories in detail. Work is now needed to explain, predict, and possibly prevent such changes in health. PMID- 11207841 TI - Quantifying the problem of abuse and neglect in adults--analysis of a statewide database. AB - BACKGROUND: Mistreatment of adults, including abuse, neglect, and exploitation, affects more than 1.8 million older Americans. Presently, there is a lack of precise estimates of the magnitude of the problem and the variability in risk for different types of mistreatment depending on such factors as age and gender. OBJECTIVES: To describe the universe of case reports received during one year in a centralized computer database maintained by the Texas Department of Protective and Regulatory Services--Adult Protective Services Division (TDPRS-APS). DESIGN: Descriptive. SETTING: Texas. PARTICIPANTS: Mistreated or neglected older people. MEASUREMENTS: The distribution of abuse types reported and population prevalence estimates of each abuse type by age and sex. RESULTS: There were over 62,000 allegations of adult mistreatment and neglect filed in Texas in 1997. Neglect accounted for 80% of the allegations. The incidence of being reported to the TDPRS-APS increased sharply after age 65. The prevalence was 1,310 individuals/100,000 > or = 65 years of age for all abuse types. CONCLUSIONS: The TDPRS database is an excellent tool for characterizing and tracking cases of reported elder mistreatment. Achieving a clearer understanding of this ever increasing public health problem can aid in the development of better interventions and prevention strategies. PMID- 11207842 TI - Weight outcomes among antidepressant users in nursing facilities. AB - OBJECTIVES: Depression is a common and treatable condition among nursing facility residents, with low body weight being a frequent concomitant concern. A common prescribing dictum is that older tricyclic antidepressants (TCAs) enhance appetite and may facilitate weight gain, while newer selective serotonin reuptake inhibitors (SSRIs) cause anorexia and resultant weight loss in older adults. Evidence is lacking on whether the small weight changes noted during short-term antidepressant efficacy trials translate into larger weight changes during prolonged treatment periods. Our main objective was to compare weight outcomes at 6 months among users of three different antidepressant groups with a control group of non-antidepressant users. A secondary objective was to determine whether antidepressant selection was associated with weight pattern before drug initiation, to capture possible prescribing bias that would affect study inferences. DESIGN: Retrospective cohort design using the Minimum Data Set--Plus (MDS+). SETTING: Kansas nursing facilities. PARTICIPANTS: 1,157 antidepressant users age 65 and older who started an antidepressant after admission and remained on the same single agent for at least 6 months, and 4,852 persons meeting the same inclusion/exclusion criteria but not receiving an antidepressant. MEASUREMENTS: Antidepressant use was identified by drug code data and divided into four groups for analysis: TCAs, SSRIs, others, and none. (Amitriptyline and trazodone were excluded because of frequent use for nondepression purposes.) Rates of clinically important loss and gain (assigned for a 10% change from baseline weight or presence of the significant loss or gain markers on the 6 month MDS assessment) and mean weight changes were compared across the four groups. Regression models were used to control for age, gender, baseline weight, confounding comorbidity, and functional variables related to eating. Previous weight patterns (loss, gain, neither, or unknown) before antidepressant initiation were compared across drug groups. RESULTS: Clinically important weight loss and gain occurred at 6 months in 14.8% and 14.4% of the sample, respectively. In unadjusted analyses, an increased likelihood of loss was found for users of SSRIs (Odds Ratio 1.57; CI 1.30, 1.90) and others (OR 1.89; CI 1.18, 3.03), compared with none. In logistic models accounting for potential confounding factors, however, SSRI use showed a modest association with gain (OR 1.31, CI 1.01, 1.70) and a trend toward a similarly modest association with loss (OR 1.28; CI 0.995, 1.64). TCA use was not associated with weight gain. When weight was examined as a continuous variable, all groups demonstrated a broad range of both loss and gain with mean-unadjusted weight changes < 3 pounds. Pairwise comparisons of adjusted differences in weight change at 6 months for SSRIs (mean loss of 1.6 pounds) and TCAs (mean gain of 0.4 pounds) were of marginal importance (P = .046) given the large sample size. No evidence was found for prescribing bias based on prior weight pattern. CONCLUSIONS: TCAs do not facilitate weight gain more than other antidepressant groups and SSRIs are not associated disproportionately with weight loss when other important clinical variables are accounted for. Small but statistically significant differences in mean weight changes between groups are largely a reflection of large sample size rather than clinically important differences. Clinicians may wish to reconsider the widely held notions that TCAs facilitate weight gain and that SSRIs place depressed older nursing facility residents at disproportionate risk for weight loss. PMID- 11207843 TI - The reform of the Israeli health care system: a comparison between older and younger consumers, one year and three years after its implementation. AB - OBJECTIVE: One of the main objectives of the National Health Insurance Law, which was implemented in Israel in January 1995, was to increase equity among different population groups and improve services for weaker populations, such as older people. It is not clear, however, whether the law's goals are being achieved. This study aimed to examine changes in the satisfaction and perceived quality of healthcare services among older people one year and three years after enactment of the law, and to compare the satisfaction and perceptions of older people with those of young adults. DESIGN: Two cross-sectional telephone surveys conducted by the JDC-Brookdale Institute. SETTING: Israel. PARTICIPANTS: Two random samples of the adult residents of Israel at the end of 1995 and at the end of 1997. Two hundred and eighteen older people (of 1,116 respondents) were included in the first survey, and 198 older people (of 1,205 respondents) were included in the second survey. Sixty-seven percent of older respondents in both surveys were 65 to 74 years old and the remaining 33% were 75 years old and over. Forty-three percent were men. Sixty-four percent reported having had at least one chronic illness. There were no differences between the two samples, with the exception of a higher percentage of new immigrants in the second survey. MEASUREMENTS: Perception of changes in the level of services, satisfaction with services, and perceived quality of care (availability, accessibility, early detection procedures). RESULTS: Older people felt there had been an improvement in the level of sick fund (who operate as health maintenance organizations [HMOs] in the United States) services since implementation of the law. The proportion reporting improvement increased from 13% in 1995 to 28% in 1997. At the same time, the proportion of older people who sensed a decline in the level of services also increased, albeit at a much lower rate (4% in 1995 and 8% in 1997). The percentage of younger adults reporting an improvement in services and the percentage reporting a decline were greater than the percentages of older people, in both surveys. Regarding access to services, 69% waited up to 15 minutes to see their physician and 56% received an appointment to see a specialist within one week; this was an improvement. While a higher proportion of younger adults received an appointment within a shorter time span in 1995, the gap had diminished by 1997. Most of the older people felt that the office hours of their family physicians, specialists, administrative services, and laboratories were convenient. The proportion of elderly reporting so increased between 1995 and 1997, and in both surveys was higher than among younger adults. CONCLUSION: The study's findings show that older people perceived an improvement in a number of areas during the first three years of the law's implementation. Their experience was similar to that of younger adults and was even better in some areas. It is necessary to continue monitoring the impact of the law on the need for health services of vulnerable groups such as the chronically ill and disabled older people. PMID- 11207844 TI - The medical interview: differences between adult and geriatric outpatients. AB - BACKGROUND: There is a perception that primary care physicians spend less time with older patients and little is known about physician and older patient satisfaction during clinical encounters. OBJECTIVE: To determine how primary care interviews of geriatric patients differ from those of other adults. DESIGN: Descriptive, analytic study. SETTING: Ten primary care sites in the United States and one in Canada, including public, voluntary, and private clinics and practices. PARTICIPANTS: Of the 544 patients, 45.6% were 65 and older and 17.8% were 75 or older. There were 127 participating physicians. MEASUREMENTS: Encounters were audiotaped and analyzed. Patients and physicians also completed exit questionnaires. RESULTS: Interview length increased significantly with age for men but not for women. Physician satisfaction did not change as patient age increased. Patient satisfaction, on the other hand decreased with age among women but not for men. Although physicians' and younger patients' perceptions of health were moderately associated, there was no association for men ages 75 and over. CONCLUSIONS: There is no evidence that physicians spend less time or are more uncomfortable with older patients. Both physician and male patient satisfaction remain stable with increasing patient age, despite greater disparity in patient and physician perceptions of health. Older female patients are less satisfied with physician visits than their younger counterparts, in the absence of changes in interview length or disparities between older female patients and their physicians in health perception. PMID- 11207845 TI - Validation of dizziness as a possible geriatric syndrome. AB - OBJECTIVE: While dizziness has traditionally been considered solely as a symptom of discrete diseases, recent findings from population-based studies of older persons suggest that it may often be a geriatric syndrome with multiple predisposing risk factors, representing impairments in diverse systems. To validate these findings, we identified predisposing risk factors for dizziness in a clinic-based population. DESIGN: Cross-sectional study. SETTING: Geriatric assessment center. PARTICIPANTS: 262 consecutive, eligible patients. MEASUREMENTS: Medical history and physical examination data were ascertained and characteristics of patients with and without a report of dizziness were compared. RESULTS: Seven factors were independently associated with a report of dizziness, namely depressive symptoms, cataracts, abnormal balance or gait, postural hypotension, diabetes, past myocardial infarction, and the use of three or more medications. Of patients with none of these risk factors, none reported dizziness. This proportion rose from 6% among patients with one factor, to 12%, 26%, and 51% among patients with two, three, and four or more factors, respectively. CONCLUSIONS: The finding of similar factors associated with dizziness in previous community-based cohorts and the present clinic-based cohort supports the possibility of a multifactorial etiology of dizziness in many older persons. A multifactorial intervention targeting the factors identified in these studies may be effective at reducing the frequency or severity of dizziness in older patients. PMID- 11207846 TI - Offspring of centenarians have a favorable lipid profile. AB - OBJECTIVES: It is well recognized that a favorable lipid profile provides protection from atherosclerotic cardiovascular disease. Because the major cause of nontraumatic death in the western world is considered to be due to cardiovascular disease, centenarians (defined here as subjects over 95 years of age) are believed to possess "atherosclerotic protective" factors. However, it is impossible to study comparatively the lipid profile in centenarians because of lack of controls. Assuming that certain genes responsible for encoding the lipid phenotype may be inherited, we studied the lipid profile characteristics of offspring of centenarians and compared them with control groups. DESIGN: Prospective cohort study. SETTING: The study was part of the Longevity Genes Project at Albert Einstein College of Medicine. PARTICIPANTS: Ashkenazi Jewish centenarians (n = 27, 98.4 +/- 10.4 years) and their offspring (n = 33, 67.4 +/- 1.4 years). The Ashkenazi Jewish offsprings' spouses, who were not related by blood to the centenarians or their offspring, were used as a control group (n = 26, 68.4 +/- 1.2 years). MEASUREMENTS: The lipoprotein profile of the offspring was compared with the above control group and to a larger control group (age and gender matched) from the National Health and Nutrition Examination Survey (NHANES) III study (without the sample weights, n = 394, 60 to 69 years). RESULTS: Female offspring of centenarians had significantly higher plasma levels of high density lipoprotein-cholesterol (HDL-C) levels compared with controls (70.2 +/- 3.1 vs 59.0 +/- 4.1 mg/dl, P = .029). Male offspring of centenarians had higher plasma levels of HDL-C levels (56.2 +/- 7.1 vs 44.3 +/- 3.4 mg/dl, P = 0.130) and significantly lower LDL-cholesterol (LDL-C) levels (95.0 +/- 6.0 vs 127.0 +/- 8.0 mg/dl, P = .009) compared with controls. CONCLUSION: Offspring of centenarians have a favorable lipid profile compared with controls. These data support the notion that a certain phenotypic lipid profile may be transmitted in families and suggest that a favorable lipid profile may play a role in longevity. PMID- 11207847 TI - Internal low energy atrial cardioversion: efficacy and safety in older patients with chronic persistent atrial fibrillation. AB - BACKGROUND: Low-energy internal atrial cardioversion is a relatively new technique based on delivery of intracardiac shocks through transvenous catheters placed into the atria or the vessels. OBJECTIVE: The aim of this study was to assess in older and younger patients with chronic persistent atrial fibrillation (AF) the efficacy and safety of transvenous low-energy internal atrial cardioversion performed without routine administration of sedatives or anesthetics. DESIGN: A prospective longitudinal study. SETTING: A cardiological university hospital. PARTICIPANTS: 82 patients, divided into older (> or = 60 years) (n = 49) and younger (n = 33) subjects. MEASUREMENTS: Atrial defibrillation threshold for internal cardioversion, measured as leading edge voltage (V) and delivered energy (J) of effective shocks, percentage of patients maintaining sinus rhythm at short-term (within 3 days) and at long-term follow up. METHODS: Patients with chronic persistent AF, treated with oral anticoagulants for at least 3 to 4 weeks, were admitted to hospital. Following a clinical work-up, patients were subjected to low-energy internal atrial cardioversion with shock delivery according to a step-up protocol. RESULTS: Internal cardioversion was effective in restoring sinus rhythm in 90% (44/49) of the older patients and in 94% (31/33) of the younger patients. Shocks were effective at a mean energy between 6 and 8 joules (range 0.9-23) and administration of sedatives or anesthetics was required during the procedure in 22% (11/49) of older and in 48% (16/33) of younger patients (P = .026 at chi square). No major complications occurred during the procedure. Pharmacological prophylaxis of AF recurrences was instituted immediately following the procedure. During inhospital stay and during the follow-up (mean 12 +/- 9 months for older patients and 15 +/- 10 months for younger patients), AF recurred in 39% (17/44) of older patients and in 16% (5/31) of younger subjects (P = .064 at chi-square). CONCLUSIONS: Internal low energy cardioversion is a very effective procedure for restoring sinus rhythm in patients with AF; it can be performed in older patients, and administration of sedatives or anesthetics can be avoided or minimized in a substantial proportion of subjects. Recurrences of AF in the long term tend to be higher in older subjects and intensive prophylaxis with antiarrhythmic drugs is required. PMID- 11207848 TI - Interventions to prevent pneumonia among older adults. AB - Pneumonia is a common cause of death in older people. Antimicrobial drugs do not prevent pneumonia and, because of increasingly resistant organisms, their value in curing infection will become more limited. Establishing new strategies to prevent pneumonia through consideration of the mechanisms of this devastating illness is essential. The purpose of this review is to discuss how pneumonia develops in older people and to suggest preventive strategies that may reduce the incidence of pneumonia among older adults. Aspiration of oropharyngeal bacterial pathogens to the lower respiratory tract is one of the most important risk factors for pneumonia; impairments in swallowing and cough reflexes among older adults, e.g., related to cerebrovascular disease, increase the risk for the development of pneumonia. Thus, strategies to reduce the volumes and pathogenicity of aspirated material should be pursued. For example, since both swallowing and cough reflexes are mediated by endogenous substance P, pharmacologic therapy using angiotensin-converting enzyme inhibitors, which decrease substance P catabolism, may improve both reflexes and result in the lowering of the risk of pneumonia. Similarly, since the production of substance P is regulated by dopaminergic neurons in the cerebral basal ganglia, treatment with dopamine analogs or potentiating drugs such as amantadine (and, of course, prevention of cerebral vascular disease, which can result in basal ganglia strokes) should affect the incidence of pneumonia. The purpose of this review is to consider promising pharmacologic treatments as methods of preventing pneumonia in older adults and to review other proven strategies, e.g., infection control and cerebrovascular disease prevention that will lessen the incidence of pneumonia. PMID- 11207849 TI - The sin of omission: a systematic review of antithrombotic therapy to prevent stroke in atrial fibrillation. PMID- 11207850 TI - Spontaneously perforated pyometra presenting as diffuse peritonitis in older females at nursing homes. PMID- 11207851 TI - Regarding clinical practice guidelines on the use of warfarin. PMID- 11207852 TI - In reply. PMID- 11207854 TI - In reply: PMID- 11207853 TI - In re colon cancer screening. PMID- 11207855 TI - Regarding atrial fibrillation and cognitive function in older people. PMID- 11207856 TI - In reply to Cheng. PMID- 11207857 TI - In re atrial fibrillation and cognitive impairment. PMID- 11207858 TI - In re atrial fibrillation. PMID- 11207859 TI - In reply to Belmin et al: PMID- 11207860 TI - In reply to Park et al: PMID- 11207861 TI - An old nun with diabetes who should not have been moved from her nunnery. PMID- 11207862 TI - Highlights of Papers in Clinical Investigations Section. PMID- 11207863 TI - Cardiovascular disease risk factors among older black, Mexican-American, and white women and men: an analysis of NHANES III, 1988-1994. Third National Health and Nutrition Examination Survey. AB - CONTEXT: There are few studies of ethnic differences in cardiovascular disease (CVD) risk factors in older populations. OBJECTIVES: To examine the association of ethnicity on CVD risk factors, after accounting for socioeconomic status (SES), and to examine health behaviors among those with CVD risk factors. DESIGN: Third National Health and Nutrition Examination Survey, 1988-1994. SETTING: Eighty-nine mobile examination centers. PARTICIPANTS: 700 black, 628 Mexican American, and 2192 white women and men age 65 to 84 years. MEASUREMENTS: Ethnicity in relation to type II diabetes mellitus, physical inactivity, abdominal obesity, hypertension, cigarette smoking and non-high-density lipoprotein cholesterol (non-HDL-C). RESULTS: After accounting for age and SES, both black and Mexican-American women had significantly higher prevalences of type II diabetes than white women. In addition, black women were significantly more likely to have abdominal obesity and hypertension and to be physically inactive than white women. Black men had significantly higher prevalences of hypertension and physical inactivity than white men. However, black men had lower prevalences of abdominal obesity than white men, and black women had lower prevalences of high non-HDL-C than white women. Among those with CVD risk factors, health behaviors were in need of improvement, especially among Mexican American women whose primary language was Spanish. CONCLUSIONS: In this national sample of older women and men, black and Mexican American women and black men were at the greatest risk for CVD. These findings parallel the heightened risk of CVD among younger ethnic minority populations and argue for appropriate primary and secondary prevention programs, modified for the language, cultural, and medical needs of older ethnic minorities. PMID- 11207864 TI - Lipoprotein(a) serum levels and vascular diseases in an older Caucasian population cohort. Italian Longitudinal Study on Aging (ILSA). AB - OBJECTIVE: To investigate elevated lipoprotein(a) [Lp(a)] levels as a risk factor for stroke, myocardial infarction, angina, intermittent claudication, and combination of the above in a cohort of unselected older individuals. DESIGN: Population cohort from one of the eight centers participating in the Italian Longitudinal Study on Aging (ILSA). SETTING: General community. PARTICIPANTS: A subsample of 446 subjects (M/F: 231/ 215, mean age: 74.5 +/- 5.7 years) of the original, randomly selected, population cohort of 704 individuals, 65 to 84 years of age, free-living or institutionalized in the Impruneta Municipality, area of Florence, Italy. MEASUREMENTS: Conventional vascular risk factors and vascular diseases defined following a two-step procedure (screening phase and confirmation on positives) using standard and validated criteria. Lp(a) levels determined by an ELISA method. RESULTS: No association was observed between elevated Lp(a) levels alone and any of the examined vascular diseases (stroke, myocardial infarction, angina, and intermittent claudication). In contrast, examining the interactions between elevated Lp(a) and conventional vascular risk factors, when elevated Lp(a) was combined with a history of smoking, a marked increase in the risk of vascular diseases combined (odds ratio [OR]: 4.12; 95% confidence interval [CI]: 1.27-13.40) was observed, much higher than that expected based on the additive effect of smoking and elevated Lp(a) alone. CONCLUSIONS: With the cautions due to the cross-sectional design of the study and the limited statistical power, these results suggest a possible synergistic effect between elevated Lp(a) levels and other pro-atherogenic factors such as smoking on the risk of vascular diseases in older individuals. PMID- 11207865 TI - Risk factors for hospitalized gastrointestinal bleeding among older persons. Cardiovascular Health Study Investigators. AB - OBJECTIVES: We sought to estimate the incidence of hospitalization for upper and lower gastrointestinal bleeding among older persons and to identify independent risk factors. DESIGN: Prospective cohort study. SETTING: The Cardiovascular Health Study (CHS). PARTICIPANTS: 5,888 noninstitutionalized men and women age 65 years or older in four U.S. communities enrolled in the CHS. MEASUREMENTS: Gastrointestinal bleeding events during the period 1989 through 1998 were identified using hospital discharge diagnosis codes and confirmed by medical records review. Risk-factor information was collected in a standardized fashion at study baseline and annually during follow-up. RESULTS: Among CHS participants (mean baseline age 73.3 years, 42% male), the incidence of hospitalized gastrointestinal bleeding was 6.8/1,000 person-years. In multivariate analyses, advanced age, male sex, unmarried status, cardiovascular disease, difficulty with daily activities, use of multiple medications, and use of oral anticoagulants were independent risk factors. Compared with nonsmokers, subjects who smoked more than half a pack per day had a multivariate-adjusted hazard ratio (HR) of 2.14 (95% confidence interval [CI] = 1.22-3.75) for upper gastrointestinal bleeding and a multivariate-adjusted HR of 0.21 (95% CI = 0.03-1.54) for lower gastrointestinal bleeding. Aspirin users did not have an elevated risk of upper gastrointestinal bleeding (HR = 0.76, 95% CI = 0.52-1.11), and users of other nonsteroidal anti-inflammatory drugs had a HR of 1.54 (95 % CI = 0.99-2.36). Low ankle-arm systolic blood pressure index was associated with higher risk of gastrointestinal bleeding among subjects with clinical cardiovascular disease but not among those without clinical cardiovascular disease. CONCLUSION: This study identifies risk factors for gastrointestinal bleeding, such as disability, that may be amenable to modification. The findings will help clinicians to identify older persons who are at high risk for gastrointestinal bleeding. PMID- 11207866 TI - Correlates of attributing new disability to old age. Study of Osteoporotic Fractures Research Group. AB - OBJECTIVES: To describe women who attribute new disability to old age and to identify demographic, medical, behavioral, and psychosocial characteristics that correlate with attributing new disability to old age. DESIGN: Prospective cohort study with 4-year follow-up. SETTING: Four geographic regions of the United States. PARTICIPANTS: 9704 women aged > or = 67 years participating in the Study of Osteoporotic Fractures. Of these, 657 who reported no disability at baseline but at follow-up reported difficulty carrying out 1 or more of 13 functional activities were eligible for our analysis. MEASUREMENTS: All women reporting difficulty in any functional activity at follow-up were asked "What is the main condition that causes you to have difficulty or prevents you from (doing the activity)?" and were shown a card listing 14 medical conditions as well as the option "old age," from which they could choose only one response. Women attributing difficulty or inability in 1 or more functional activities to old age were classified as attributing new disability to old age. We examined the relationship between attributing new disability to old age and the following characteristics measured at baseline: age, level of education, medical comorbidity, cognitive function, body mass index (BMI), gait speed, grip strength, visual acuity, physical activity level, smoking status, social network level, and depressed mood. RESULTS: Overall, 13.5% of women attributed new disability to old age. Age was a strong independent correlate of attributing new disability to old age: compared with women age 67 to 69, the odds of attributing new disability to old age for women age 70 to 79 was 3.6 times as large (95% confidence interval [CI] = 1.6-8.3), and for women age 80 or over was 5.5 times as large (95% CI = 2.1-14.7). The only other characteristic that remained an independent correlate of attributing new disability to old age was grip strength; for each decile decrease in grip strength, a woman's odds of attributing new disability to old age increased by 9% (odds ratio [OR] = 1.09, 95% CI = 1.01 1.19). CONCLUSIONS: Despite great advances in geriatric medicine, old age is still perceived as a causal agent in functional decline, especially among our oldest patients. Further study is needed to determine whether, how often, and under what circumstances older adults who attribute new disability to old age have medical conditions amenable to interventions that could preserve their functioning and improve their quality of life. PMID- 11207867 TI - Medical care for nursing home residents: differences by dementia status. Epidemiology of Dementia in Nursing Homes Research Group. AB - OBJECTIVE: To understand the use of medical services by nursing home residents. DESIGN: Descriptive, longitudinal study comparing medical service use of residents by dementia status and describing the use of medical services following detection of fever or infection. SETTING: Fifty-nine randomly selected nursing homes in Maryland from 1992 to 1995. PARTICIPANTS: 2,153 residents admitted to one of 59 randomly selected nursing homes. MEASUREMENT: A panel of psychiatrists and neurologists ascertained dementia based on review of medical records, interview data with significant others and nursing staff, and results of a cognitive exam. Medical service use was abstracted from medical records. BACKGROUND: Understanding the use of medical services by nursing home residents as distinct from services provided by the nursing home is important, particularly as new medical care models are tested. This study compares the medical service use of residents by dementia status and describes the use of medical services following detection of fever or infection. RESULTS: Residents with dementia compared with those without dementia had lower annual rates of physician visits (10.2 vs 12.7, P < .001) and hospitalizations (0.9 vs 1.2, P < .001), virtually the same rate of emergency department visits, and similar lengths of stay in the hospital. Subsequent to infection, a lower proportion of residents with dementia had either a physician visit, an emergency department visit, or a hospital admission compared with residents without dementia (27.2% vs 32.2%, P < .001). In 87% of infections, an antibiotic was used, implying meaningful contact with a physician. Residents with dementia compared with those without dementia had fewer physician visits subsequent to fevers (20.6% vs 29.9%, P < .001) and infections (21.8% vs 27.5%, P < .001). CONCLUSIONS: The association of less medical service use by individuals with dementia compared with those without dementia may reflect differences in health status or implicit end-of-life decision-making and a proclivity toward less-aggressive treatment for these individuals. PMID- 11207868 TI - State practice variations in the use of tube feeding for nursing home residents with severe cognitive impairment. AB - OBJECTIVE: To describe the differences in prevalence of tube feeding among states and to examine possible factors that could explain practice patterns. DESIGN: Analysis of random samples from an interstate data bank comprised of the Minimum Data Set (MDS), a standardized, federally mandated assessment instrument for nursing home residents. SETTING: Nursing homes in four states participating in a federal demonstration project of case mix payment plus five others with existing MDS data systems. PARTICIPANTS: Individuals 65 years of age and older (N = 57,029), who had very severe cognitive impairment, including total dependence in eating, and who resided in nursing homes during 1994, the most recent year for which uniform data were available. MEASUREMENTS: State-by-state differences in prevalence of tube feeding, controlling for demographic and clinical variables. RESULTS: The prevalence of tube feeding ranged from 7.5% in Maine to 40.1% in Mississippi. Each state had a significantly elevated prevalence of tube feeding compared with Maine, with odds ratios (ORs) ranging from 1.50 to 5.83, P < .001. Specific directives not to provide tube feeding (OR 0.41, P < .001), and white race (OR 0.45, P < .001) were strongly and negatively associated with tube feeding. CONCLUSIONS: Wide regional variations exist in the use of tube feeding of nursing home residents with equivalent impairments. Sociodemographic factors could be important, but more study is needed to determine whether physician characteristics, such as race, attitudes, or knowledge, have an impact and to clarify medical standards for the use of tube feeding in this population. PMID- 11207869 TI - Life-sustaining treatment and assisted death choices in depressed older patients. AB - OBJECTIVES: The major purpose of this study was to examine the effect of depressed mood in older, medically ill, hospitalized patients on their preferences regarding life-sustaining treatments, physician-assisted suicide (PAS), and euthanasia and to determine the degree to which financial constraints affected their choices. DESIGN: Cross-sectional study. SETTING: General medical hospital. PARTICIPANTS: One hundred fifty-eight medically hospitalized, nondemented patients age 60 or older, mean age 74.1 (range 60-94). The sample was divided, based on Center for Epidemiologic Studies-Depression (CES-D) scores, into a depressed group (n = 71) and a nondepressed control group. MEASUREMENTS: Subjects underwent a structured interview evaluating their life-sustaining treatment choices and whether they would accept or refuse PAS or euthanasia under a variety of hypothetical conditions. These choices were reevaluated with the introduction of financial impact. In addition, assessment included measures of depression, suicide, cognition, social support, functioning, and religiosity. RESULTS: Depression was found to be highly associated with acceptance of PAS and euthanasia in most hypothetical clinical scenarios in addition to patients' current condition. Compared with nondepressed people, depressed respondents were 13 times as likely to accept PAS when considering their current condition (95% confidence interval [CI] 1.68-110.98), and over twice as likely to accept PAS when facing a hypothetical terminal illness or coma. Depression alone was weakly associated with life-sustaining treatment choices but, when financial impact was introduced, significantly more depressed subjects refused treatment options they had previously desired than did nondepressed subjects. The presence of suicidal ideation, even passive ideation, was strongly predictive of life-sustaining treatment refusals and increased interest in PAS and euthanasia. Depression's effect on acceptance of PAS was confirmed by logistic regression, which also showed that religious coping was significantly correlated with less interest in PAS in two hypothetical scenarios. CONCLUSION. Depressed subjects and even subjects with subtle, passive suicidal ideation were markedly more interested in PAS and euthanasia than nondepressed subjects in hypothetical situations. Depressed subjects were also particularly vulnerable to rejecting treatments if financial consequences might have resulted. PMID- 11207871 TI - Late-onset multiple sclerosis. AB - OBJECTIVE: The onset of multiple sclerosis (MS) after age 50 is infrequent and presents a diagnostic challenge. The purpose of the present study was to review the prevalence, presentation, and clinical characteristics of late-onset MS. DESIGN: A retrospective chart review. SETTING: The Multiple Sclerosis Center at Sheba Medical Center, Israel. PARTICIPANTS: 640 patients with a definite diagnosis of MS. MEASUREMENTS: Diagnosis of MS was established according to Poser criteria and confirmed by brain magnetic resonance imaging (MRI) using our unit's computerized database. Late-onset MS was defined as the first presentation of clinical symptoms after the age of 50 years. For each patient, age, gender, clinical presentation, disease course, neurological involvement, disease duration, neurological disability assessed, and Progression Index (PI) were analyzed. All patients were interviewed using the structured clinical interview for DSM-IV, SCID-lifetime Hebrew version. RESULTS: Of 640 MS patients, 30 (4.6%) were diagnosed as suffering from late-onset MS. Mean age at onset was 53.5 +/- 3.1, range 50 to 62 years. Female to male ratio was 1.73:1. Mean disease duration was 7.6 years, range 2 to 11 years. In 50% of patients the disease course was relapsing-remitting. Motor symptoms were the most common neurological presentation at onset (63.3%). Major depressive episode was diagnosed in 6 out of 30 patients (20%) in the two years prior to the diagnosis of MS. After a mean disease duration of 7.6 years there was a marked increase in sphincteric and cerebellar involvement. In addition 7 out of 30 patients had suffered a major depressive episode within 4 years of diagnosis. Mean PI was 0.81, suggesting rapid neurological deterioration. CONCLUSIONS: Late-onset MS is not rare and may present as major depression and, although neurological presentation at onset is similar to that of young adults, progression to disability is more rapid and a primary progressive course is more prevalent. PMID- 11207870 TI - Guar gum reduces postprandial hypotension in older people. AB - OBJECTIVE: To determine whether slowing of gastric emptying and glucose absorption with guar gum would reduce the fall in blood pressure after an oral glucose load in older subjects. DESIGN: A randomized, experimental, cross-over study. SETTING: Department of Nuclear Medicine, Royal Adelaide Hospital, Adelaide, SA, Australia. PARTICIPANTS: Ten healthy subjects, age 67 to 78. MEASUREMENTS: Simultaneous measurements of gastric emptying, blood pressure, blood glucose, serum insulin, and oral glucose absorption (3-O-methyl-D-glucose [3-OMG]) on two occasions after ingestion of 300 mL water containing 50 g glucose and 30 mL lemon juice, 3 g 3-OMG labeled with 99mTc-sulphur colloid; with or without 9 g guar gum. Blood pressure and gastric emptying were monitored for 180 minutes. RESULTS: The magnitude of the falls in systolic (P = .02), diastolic (P < .05), and mean arterial (P = .05) blood pressure were less, and gastric emptying slower (P < .05), after guar. Blood glucose, insulin, and 3-OMG concentrations were reduced (P < .001 for all) by guar. 3-OMG concentrations were inversely related to the intragastric retention of glucose (r = -0.72, P = .02) and blood pressure was inversely related to 3-OMG (r = -0.64, P < .05) after the drink without guar. The blood glucose concentration was related to 3-OMG (r > 0.64, P < .05). CONCLUSION: Guar gum reduces the magnitude of the fall in blood pressure after oral glucose. Slowing of gastric emptying and glucose absorption may represent a novel approach to the treatment of postprandial hypotension. PMID- 11207872 TI - Methodologic issues in conducting research on hospitalized older people. AB - OBJECTIVE: To describe challenges in conducting research with hospitalized geriatric patients. DESIGN: Quasi-experimental longitudinal study with inperson interviews at baseline and discharge and a three-month postdischarge telephone interview. Study protocol required baseline interviews within 48 hours of admission for patients or 72 hours for proxies. SETTING: 813-bed urban teaching hospital. PARTICIPANTS: 240 patients, mean age 83.8 years, at moderate to high risk for functional decline during hospitalization, admitted from the emergency room to a general medical unit. MEASUREMENTS: Delays starting or interruptions continuing interviews; patient and environmental conditions potentially affecting data quality; and information on proxy use. RESULTS: Timely access to patients or proxies was a major difficulty, resulting in the screening of only 53.1% of 867 potentially eligible patients. Multiple patient contacts and visits were required to complete interviews. Only 61.3% of baseline and 28.1% of follow-up interviews were completed on the initial day of contact. Despite having on-site interviewers 7 days a week, 29% of discharge interviews were conducted by telephone. Interviews were >90% complete in 487 of 503 of encounters (97%). Baseline delays and interruptions were usually due to the presence of medical staff, off-unit tests, patient illness, nurse unavailability for interview, and need for a proxy. Most in-hospital interviews were conducted with others present. Proxies were required for approximately one-third of patients at all three interviews. CONCLUSION: Conducting clinical research with older adults in the current inpatient setting, where patients are more severely ill yet have shorter lengths of stay now than in the past, proves a challenging yet achievable goal. Effective procedures for negotiating the acute care environment are critical to successful studies. PMID- 11207873 TI - Hormone replacement therapy and fractures in older adults. AB - Estrogen deficiency in women is associated with accelerated bone loss, and estrogen replacement therapy has been proven to be effective in preventing osteoporosis and fractures in postmenopausal women. The introduction of selective estrogen receptor modulators that have an estrogen-like effect on the skeleton but have a different pattern of effects on other tissues may have an important role in the management of osteoporosis in women in the near future. In men, androgen deficiency has been shown to be associated with osteoporosis. Although androgen replacement in hypogonadal men may decrease bone resorption and increase bone mass, long-term placebo-controlled trials are needed to better define the benefits and risks of such therapy before it can be recommended. Sex hormone deficiency is linked to the development of osteoporosis in both women and men. In women, hormonal replacement by estrogen or the newly developed selective estrogen receptor modulators may prevent the development of osteoporosis and its related fractures. In men, there is early evidence that testosterone replacement therapy may enhance bone mass in hypogonadal men. PMID- 11207874 TI - Pain management in older adults: prevention and treatment. AB - The release of guidelines in 1998 by the American Geriatrics Society on "The Management of Chronic Pain in Older Persons" was a breakthrough in helping to manage pain in this population. Already advances have fostered a need to update recommendations. This article focuses on the treatment strategies available for seniors that are likely to help to fulfill the obligation to relieve pain and suffering in patients. A review was done of the literature using Medline and other search techniques. New pain scales have been developed with seniors in mind and greater testing of older scales in elderly populations have helped to identify measures of pain more suited to frail seniors. Advances in cyclooxygenase inhibition selectivity, alternative medicine, and progress in the identification of nonopioid pain receptors and the development of products to target them are just a few of changes that have altered the way clinicians think about treating pain. The use of hospice in end-of-life palliative care is a valuable resource for clinicians managing pain at that phase in care as well. Tools are available to prevent and treat pain successfully in seniors. Educating clinicians about available assessment tools, techniques and interventions may be the biggest challenge to comforting the older adult in pain. PMID- 11207875 TI - Suboptimal prescribing in older inpatients and outpatients. AB - Investigators searched Medline and HealthSTAR databases from January 1, 1985 through June 30, 1999 to identify articles on suboptimal prescribing in those age 65 years and older. A manual search of the reference lists from identified articles and the authors' article files, book chapters, and recent reviews was conducted to identify additional articles. The definitions for various types of suboptimal prescribing (polypharmacy, inappropriate, and underutilization) are numerous, and measurement varies from study to study. The literature suggests that suboptimal prescribing is common in older outpatients and inpatients. Moreover, there is significant morbidity and mortality associated with suboptimal prescribing for these older patients. Evidence from well-controlled studies suggests that multidisciplinary teams and clinical pharmacy interventions can modify suboptimal drug use in older people. Future research is necessary to measure and test other methods for tackling this major public health problem facing older people. PMID- 11207876 TI - Practice guideline for evaluation of fever and infection in long-term care facilities. AB - The elderly population (i.e., persons aged > or = 65 years) in the United States is rapidly expanding and will nearly double in number over the next 30 years. It is estimated that >40% of persons aged > or = 65 years will require care in a long-term care facility (LTCF), such as a skilled nursing facility (SNF), at some point during their lifetime. For the most part, residents of LTCFs are very old and have age-related immunologic changes, chronic cognitive and/or physical impairments, and diseases that alter host resistance; therefore, they are highly susceptible to infections and their complications. The diagnosis of infections in residents of LTCFs is often difficult because LTCFs differ from acute-care facilities in their goals of care, staffing ratios, types of primary care providers, availability of laboratory tests, and criteria for infections. Consequently, guidelines and standards of practice used for diagnosis of infections in patients in acute-care facilities may not be applicable nor appropriate for residents in LTCFs. Moreover, the clinical manifestations of diseases and infections are often subtle, atypical, or nonexistent in the very old. Fever may be low or absent in LTCF residents with infection. The initial evaluation of an LTCF resident suspected of an infection may not be done by a physician. Although nurses commonly perform initial assessments for infection in residents of LTCFs, further studies are needed to determine the appropriateness and validity of this practice. Provided there are no directives (advance or current by resident or caregiver) limiting diagnostic or therapeutic interventions, all residents of LTCFs with suspected symptomatic infection should have appropriate diagnostic laboratory studies done promptly, and the findings should be discussed with the primary care clinician (see Recommendations). The most common infections among LTCF residents are urinary tract infections, respiratory infections, skin or soft tissue infections, and gastroenteritis. Decisions concerning possible transfer of an LTCF resident to an acute-care facility are best expressed through an advance directive or, when not available, through transfer policies developed by the LTCF. In general, LTCF residents have been transferred to an acute-care facility when any of the following conditions exist: (1) the resident is clinically unstable and the resident or family goals indicate aggressive interventions should be initiated, (2) critical diagnostic tests are not available in the LTCF, (3) necessary therapy or the mode of administration of therapy (frequency or monitoring) are beyond the capacity of the LTCF, (4) comfort measures cannot be assured in the LTCF, and (5) specific infection-control measures are not available in the LTCF. PMID- 11207877 TI - Education in geriatric Medicine. AGS Education Committee and Public Policy Advisory Group (PPAG). PMID- 11207878 TI - Genetic testing for late-onset Alzheimer's disease. AGS Ethics Committee. PMID- 11207879 TI - New drugs for old folks: the evidence-based argument for newer antidepressants. PMID- 11207880 TI - Oral health and the role of the geriatrician. PMID- 11207881 TI - In re Daytime sleepiness and mortality. PMID- 11207882 TI - In reply. PMID- 11207883 TI - Patients with late-onset depression have poor cognitive function at old age. PMID- 11207884 TI - Giant incidental cardiac mass compatible with myxoma in a 92-year-old woman. PMID- 11207885 TI - Association between oxybutynin and neuropsychiatric adverse effects not confirmed in daily practice. PMID- 11207886 TI - Charles Bonnet syndrome and opioids. PMID- 11207887 TI - The Newcastle protocol for carotid sinus massage. PMID- 11207888 TI - Implementing a program in the surgical specialties--what is out there and how to begin. PMID- 11207889 TI - Are primary biliary cirrhosis and autoimmune cholangitis reflective of the pendulum of a clock and therefore represent a 'phase' of the same disease? PMID- 11207890 TI - New hepatitis viruses: contenders and pretenders. AB - Following the development of tests for hepatitis C virus and hepatitis E virus infection, it became clear that there remained cases of hepatitis that were non-A E. Such cases provided impetus for the search for additional hepatitis viruses and, by using molecular techniques, several candidates were identified. An enteric agent responsible for sporadic non-A and non-E hepatitis was tentatively called hepatitis F virus. However, the lack of any corroborating reports has cast doubt on its status as a true hepatitis virus. Two groups independently reported the isolation of a blood-borne virus, designated as hepatitis G virus (HGV) and GB virus C (GBV-C) by their respective discoverers. They were later shown to be isolates of the same virus. While the virus has a high prevalence in cases of non A-E hepatitis, it also has a high prevalence in the appropriate control groups and convincing evidence for its replication in the liver is lacking. Another possible hepatitis virus, TT virus, was discovered in the blood of a patient with post-transfusion non-A-E hepatitis. By using PCR primers designed to overcome the high nucleotide sequence divergence, TT virus was found to be ubiquitous with a worldwide distribution. A disease association is thus unlikely. Most recently, a DNA virus designated as SEN-V has been announced as a major cause of non-A-E hepatitis. Based on limited data available to researchers, SEN-V is the most convincing contender for the new hepatitis virus title. However, the lessons learnt from the hepatitis virus pretenders will need to be applied to SEN-V and any future contenders. PMID- 11207891 TI - Role of hiatus hernia and gastric mucosal atrophy in the development of reflux esophagitis in the elderly. AB - BACKGROUND AND AIMS: The pathogenetic mechanism responsible for the increased prevalence of reflux esophagitis in the elderly remains controversial. The aim of this study was to determine if an increased occurrence of hiatus hernia (HH) and/or a lower rate of gastric mucosal atrophy (GMA) are the main causes of the increased prevalence of reflux esophagitis in elderly patients. METHODS: The prevalence of HH, GMA, and reflux esophagitis was investigated by reviewing the endoscopic films of 2788 consecutive patients examined during a 3-year period. RESULTS: The prevalence of esophagitis in males was higher than in females (11.6% vs 7.6%, P< 0.0005). The prevalence of reflux esophagitis and HH was found to increase with age in females, but not in male patients. The prevalence of reflux esophagitis in hernia-positive patients also increased with age in women, but not in men. Age, male gender, presence of HH, and closed-type of GMA were significant risk factors for the prevalence of esophagitis (P=0.0001, 0.0229, <0.0001, <0.0001, respectively). In addition, the risk ratios of HH and low-grade GMA for reflux esophagitis increased with age, and this tendency was higher in female patients than in males. CONCLUSIONS: Aging, male gender, HH and closed-type GMA are most likely the risk factors of endoscopically proven reflux esophagitis in Japanese patients. PMID- 11207892 TI - Ulcer in the gastric tube for esophageal replacement: a comparison of 12 esophageal cancer patients with or without postoperative radiotherapy. AB - BACKGROUND AND AIMS: Ulcer in the gastric tube for esophageal replacement, which was caused by peptic factors or postoperative radiotherapy (Rx), are occasionally reported. The aim of this study was to clarify the clinicopathologic features of the ulcers in the gastric tube. METHODS: In 62 patients with a reconstructed gastric tube, after esophagectomy for esophageal cancer, esophagogastroduodenoscopy was performed. Ulcers of the gastric tube were detected in 12 patients: six with postoperative Rx and six without Rx. The 12 patients with gastric tube ulcers (GU-group) were reviewed and compared to the remaining 50 patients without ulcers of the gastric tube (Control-group). Clinicopathologic features of gastric tube ulcers were compared between the patients with and without Rx. RESULTS: There was no difference in any parameter between the patients of the GU- and Control-groups. Comparing the patients of the GU-group with and without Rx, the ulcers of the gastric tube in the patients without Rx were frequently located in the lower part of the gastric tube (P = 0.067), detected in a later period after surgery (P = 0.055), associated with cervical esophagitis (P = 0.03), and less associated with gastritis (P = 0.03). In three patients of the GU-group without Rx, Helicobacter pylori was detected in the gastric tube. Two of the three patients had a history of peptic ulcers before surgery, and had recurrence of the gastric tube ulcers. CONCLUSIONS: Gastric tube ulcers without postoperative Rx may have different characteristics compared to those induced by Rx. PMID- 11207894 TI - Vascularity of advanced gastric carcinoma: evaluation by using power Doppler imaging. AB - BACKGROUND: We investigated the vascularity of advanced gastric adenocarcinomas by using percutaneous power Doppler imaging. METHODS: Seventeen patients with gastric cancer and 10 without a gastric tumor, but with a slightly thick gastric wall in the B-mode ultrasound, were investigated with the use of power Doppler imaging. The color signals of the gastric lesion were graded as follows: 1, no color signals or the same as the surroundings; 2, color signals were slightly increasing; and 3, color signals were obviously increasing. RESULTS: The color signals of three patients were graded 1, those of eight patients were graded 2 and those of six patients were graded 3 in the gastric cancer group. The color signals of all 10 patients without a gastric tumor were grade 1. This difference was statistically significant (P = 0.0002). CONCLUSIONS: Power Doppler imaging showed vascularity of gastric cancer increasing in the majority of patients (14 of 17: 82%). Thus, power Doppler imaging might be a good screening examination method for gastric cancer. PMID- 11207893 TI - Shift of the gastric T-cell response in gastric carcinoma. AB - BACKGROUND AND AIMS: The etiology and pathophysiology of stomach carcinoma is complex, and the mechanism whereby H. pylori directly or indirectly induces carcinoma remains unclear. In this study, interleukin (IL)-8, IL-4 and interferon (IFN)-gamma were measured in the tissue culture supernatant of gastric organ cultures from subjects with chronic gastritis with or without H. pylori infection, and with or without gastric cancer and gastric dysplasia. RESULTS: Interleukin-8 levels were higher in cancer- and H. pylori-infected gastritis subjects than in H. pylori-negative subjects (12.95 +/- 3.16, 10.48 +/- 1.55 and 4.49 +/- 1.28 ng/mL, respectively). Elevated levels of IFN-gamma were detected in both H. pylori-infected and non-infected subjects with uncomplicated gastritis (72.23 +/- 19.0 and 34.61 +/- 5.30 pg/mL) and in non-infected dysplasia subjects (88 +/- 20.5 pg/mL). Background levels of IL-4 (< or = 9.4 pg/mL) in uncomplicated gastritis subjects and relatively high levels of IL-4 in dysplasia subjects (25.8 +/- 7.3 pg/mL) were detected. In contrast, trace amounts of IFN gamma (16.01 +/- 0.35 pg/mL) and high levels of IL-4 (42.81 +/- 8.49 pg/mL) in gastric biopsy culture supernatants were found in cancer subjects. Mucosal IL-4 levels (but not IL-8 levels) correlated with infection and mucosal anti-H. pylori immunoglobulin G antibody. CONCLUSIONS: The significant differences between gastritis with and without cancer and dysplasia indicated a shift from a Th1 to a Th2 helper cell pattern of cytokine secretion. This study has identified a local mucosal defect in gastric cancer. The near absence of IFN-gamma production from the mucosa at the margins of the tumor may be a critical factor in promoting growth of neoplastic cells. PMID- 11207895 TI - Predictors of health-care consultation for recurrent abdominal pain among urban schoolchildren in Malaysia. AB - AIM: To look at the predictors of health-care consultation for recurrent abdominal pain among urban schoolchildren in Malaysia. METHODS: Recurrent abdominal pain was defined as at least three episodes of abdominal pain, severe enough to affect a child's activities over a period longer than 3 months. A health-care consulter was defined as a child who had been brought to see a doctor regarding recurrent abdominal pain at least once in the past year. Children aged between 9 and 15 years were randomly chosen from schools in the city of Petaling Jaya, given questionnaires to fill in and interviewed to determine whether they fulfilled the above criteria for having symptoms of recurrent abdominal pain and for being a consulter. Bivariate analysis and multiple logistic regression analysis were performed on the data obtained. RESULTS: One hundred and forty three (9.61%) children fulfilled the criteria for recurrent abdominal pain out of a total of 1488 schoolchildren interviewed. There were 65 (45.5%) consulters and 78 (54.5%) non-consulters. Among the consulters, the male to female ratio was 1:1.4, while among the non-consulters, the ratio was 1:1.1. On bivariate analysis, the Chinese had a significantly lower likelihood to consult a doctor (P = 0.02), while the other two races did not show any increase in consultation (Malays, P = 0.08; Indians, P = 0.21). Among those with severe pain, there was a significantly higher prevalence of consulters (P < 0.01). Furthermore, those whose sleep was interrupted by abdominal pain were more likely to consult (P < 0.01). Children who had consulted a doctor were more likely to be missing school because of abdominal pain (P < 0.01). Following multiple logistic regression analysis, ethnicity was no longer a significant predictor. CONCLUSIONS: Approximately 45.5% of schoolchildren with recurrent abdominal pain in an urban setting were brought to see a doctor. Predictors of recent health-care consultation were school absence, pain severity and interruption of sleep caused by abdominal pain. PMID- 11207896 TI - Dietary fiber fraction of germinated barley foodstuff attenuated mucosal damage and diarrhea, and accelerated the repair of the colonic mucosa in an experimental colitis. AB - BACKGROUND AND AIMS: Germinated barley foodstuff (GBF) contains protein and insoluble dietary fiber. We have previously shown in ulcerative colitis patients and a colitis model that GBF feeding attenuates mucosal damage by increasing luminal butyrate levels. However, the detailed mechanism remains unclear because of its heterogeneous nature. The present study was carried out to: (i) evaluate the active ingredient in GBF; and (ii) examine its effect on the repair process in colonic inflammation by using a dextran sulfate sodium (DSS) colitis model. METHODS: Colitis was induced by feeding a diet containing 0.5-3.5% DSS to male Sprague-Dawley rats. (i) Active ingredient: GBF was fractionated enzymatically into fiber- and protein-rich fractions. Each fraction was administered to DSS colitis rats. Clinical signs, cecal short chain fatty acid concentrations and serum alpha1-acid glycoprotein (AAG) levels were determined. (ii) Effect on mucosal repair: GBF with or without salazosulfapyridine (SASP), or SASP alone was administered to rats after the onset of colitis. Seven days after initial treatment, the number of epithelial cells in HE sections was evaluated morphologically in a blind fashion and serum AAG was determined. RESULTS: (i) Germinate barley foodstuff and GBF-fiber significantly attenuated the clinical signs of colitis and decreased serum AAG levels, with a significant increase in cecal butyrate production, while GBF-protein did not. (ii) Treatment with GBF alone and GBF plus SASP significantly accelerated colonic epithelial repair and improved clinical signs. CONCLUSIONS: These findings suggest that the fiber fraction of GBF may effectively enhance luminal butyrate production, and thereby accelerate colonic epithelial repair in colitis. PMID- 11207897 TI - Binding sites for progastrin-derived peptides in colonic crypts. AB - BACKGROUND AND AIMS: Gastrin17gly acts as a growth factor for the colonic mucosa. Studies on the binding properties of the receptor involved in transducing the proliferative effects have generally been confined to colorectal carcinoma cell lines, and no investigation of gastrin17gly receptors on normal colonocytes has yet been reported. The aim of this study was to investigate the binding of 125I [Met15]-gastrin17gly to normal colonic crypts. METHODS: Crypts were released from normal rat and rabbit colonic mucosa by treatment with EDTA and isolated by centrifugation. The binding of 125I-[Met15]-gastrin17gly was measured in displacement experiments with increasing concentrations of either gastrin17gly, gastrin17 or gastrin receptor antagonists. The concentrations required for 50% inhibition were determined by the use of curve fitting. RESULTS: 125I-[Met15] Gastrin17gly bound to both rat and rabbit crypts, and displacement experiments with unlabeled gastrin17gly revealed that the IC50 values were 1.0 +/- 0.6 and 0.6 +/- 0.2 micromol/L, respectively. Binding was also competed by gastrin17, with IC50 values of 2.4 +/- 1.7 and 2.4 +/- 0.7 micromol/L, respectively. Binding was inhibited by the non-selective gastrin/CCK receptor antagonists proglumide and benzotript, but not by the cholecystokinin (CCK)-A receptor antagonist L364 718, or the gastrin/CCK-B receptor antagonist L365 260. CONCLUSION: We conclude that the gastrin17gly binding site on normal colonic crypts has properties consistent with the gastrin/CCK-C receptor. PMID- 11207898 TI - Comparison of the expression of ABH/Lewis-related antigens in polypoid and non polypoid growth types of colorectal carcinoma. AB - BACKGROUND AND AIMS: Colorectal tumors can be classified based on their growth pattern into the polypoid growth-type (PG-type) and non-polypoid growth-type (NPG type). To ascertain whether there is any relationship between the expression of particular blood group-related antigens (A, B, H, Lewis (Le)a, sialyl Le(a), Le(x), sialyl Le(x)) in a colorectal tumor, and a tumor having polypoid or non polypoid growth, we examined 78 PG-type and NPG-type colorectal cancers. METHODS: Fourteen PG-type and 64 NPG-type colorectal carcinomas were subjected to immunohistochemical analyses by using monoclonal antibodies against A, B, H, Le(a), sialyl Le(a), Le(x) and sialyl Le(x). RESULTS: The patients with NPG-type carcinomas had a significantly younger age of onset, significantly smaller maximal tumor diameter, significantly higher rate of lymph node metastasis and significantly worse prognosis than those with PG-type carcinomas. Among the 32 tumors of patients with blood type A or AB, isoantigen A was expressed in a significantly larger percentage of NPG-type carcinomas than PG-type carcinomas (95.8 vs 62.5%, respectively; P=0.014). Among all 78 tumors, sialyl Le(x) antigen was expressed in a significantly larger percentage of NPG-type than PG-type carcinomas (90.6 vs 64.3%, respectively; P=0.010). Multivariate analysis using the logistic regression model revealed that isoantigen A and sialyl Le(x) expression were independent predictive risk factors for the development of NPG type colorectal carcinoma. CONCLUSIONS: These data suggest that the expression of isoantigen A and sialyl Le(x) in a colorectal carcinoma partially determines whether the tumor will have polypoid or non-polypoid growth. PMID- 11207899 TI - Polymorphic expression of decay-accelerating factor in human colorectal cancer. AB - BACKGROUND: We have previously shown that expression of decay-accelerating factor (DAF), a complement regulatory protein, is enhanced immunohistochemically on the luminal surface of cancer glands in human colorectal cancer and is detected in stool specimens of patients with colorectal cancer. The amount of DAF present in the stools might be influenced by the stability of DAF on the cell surface which is regulated by biochemical properties such as glycosylation of the protein. In the present study, to help elucidate the mechanism for the release of DAF from human colorectal cancers, we biochemically analyzed DAF expression by western and northern blotting by using surgically resected specimens of colorectal cancers. METHODS: Surgically resected colorectal cancer tissues were obtained from 10 patients. Expression of DAF was determined by western and northern blotting, and glycosylation of DAF protein was analyzed with glycosidase digestion. RESULTS: Northern blot analysis demonstrated that the expression of DAF mRNA in colorectal cancer was enhanced two- to threefold compared with normal tissues. In western blotting, expression of DAF protein in the cancer tissue was increased, and heterogeneity in the apparent molecular weight of DAF was observed among patients. When o-linked sugars were removed, this heterogeneity of DAF size diminished. CONCLUSIONS: The polymorphic expression of DAF in colorectal cancer is likely to reflect variability in the o-glycosylation of the protein. We speculate that this variability could affect the stability of DAF on the surfaces of cancer cells and, in turn, the amount of DAF shed into the stools of colorectal cancer patients. PMID- 11207900 TI - Hepatic steatosis in chronic hepatitis C virus infection: prevalence and clinical correlation. AB - BACKGROUND AND AIMS: Hepatic steatosis is a histological characteristic in patients with chronic hepatitis C virus (HCV) infection. The aim of this study was to evaluate the prevalence of hepatic steatosis in Chinese patients with chronic hepatitis C, and to look for possible correlation with various histopathological changes and to look for possible correlation with various clinical and pathologic variables. METHODS: One hundred and six patients were enrolled, and patients with alcoholism or diabetes mellitus were excluded. Clinical, biochemical and virologic data, including HCV genotype and serum HCV RNA titer and histological findings, were compared between patients with and without hepatic steatosis. RESULTS: Fifty-five (52%) of the 106 patients with chronic hepatitis C had hepatic steatosis. Patients with hepatic steatosis had significantly higher mean serum levels of triglyceride and gamma-glutamyl transpeptidase, higher body mass index, and a higher incidence of obesity compared with patients without hepatic steatosis. No significant differences in serum HCV-RNA titer and HCV genotype or the response to interferon therapy were noted between the two groups. Histological analysis showed patients with hepatic steatosis had a significantly higher mean fibrotic score than patients without hepatic steatosis (1.9 +/- 1.2 vs 1.3 +/- 1.0; P = 0.016). There were no significant differences in the severity of necroinflammation, the presence of lymphoid aggregation/follicle or bile duct damage between the two groups. Multivariate logistic regression analysis showed that independent predictors associated with hepatic steatosis were obesity or a histology fibrotic score of > or = 2. CONCLUSION: It was found that 52% of Chinese patients with chronic hepatitis C had hepatic steatosis. Patients with hepatic steatosis were more frequently obese and had more severe hepatic fibrosis. PMID- 11207901 TI - Serum amino-terminal propeptide of type III procollagen and 7S domain of type IV collagen correlate with hepatic iron concentration in patients with chronic hepatitis C following alpha-interferon therapy. AB - BACKGROUND: It has been reported that chronic infection with hepatitis C virus is associated with excess iron deposits in the liver of subjects who are neither alcoholics nor recipients of blood transfusions. However, little is known about the relationship between hepatic iron concentration (HIC) and the serum levels of hepatic fibrogenesis markers, which were caused by interferon therapy for chronic hepatitis C. Therefore, changes in the serum amino-terminal propeptide of type III procollagen (P-III-P) and the 7S domain of type IV collagen (7S-IV) in 16 patients treated with alpha-interferon (IFN-alpha) were studied, and their HIC and histological assessment evaluated. Hepatic iron concentrations were measured by using liver biopsy specimens obtained before and 6 months after the cessation of treatment. METHODS AND RESULTS: Eight subjects (50%) who had normal alanine transaminase levels at 6 months after therapy showed significantly lowered HIC, and attenuated hepatic iron staining with decreased serum levels of P-III-P and 7S-IV compared to the remaining subjects. The HIC was significantly correlated with the serum levels of P-III-P and 7S-IV in all subjects. CONCLUSIONS: These findings suggest that IFN-alpha treatment may decrease stimuli for fibrogenesis, at least in part, by reducing the hepatic iron deposition in patients with chronic hepatitis C. PMID- 11207902 TI - Clinical significance of TT virus in chronic hepatitis C. AB - BACKGROUND AND AIMS: Much is still unknown about the clinical significance of TT virus (TTV), which has been reported as a candidate for non A-G hepatitis virus. The aim of this study was to clarify the clinical significance of TTV in patients coinfected with TTV and hepatitis C virus (HCV). METHODS: The 95 subjects studied had chronic hepatitis C (CHC), and underwent interferon (IFN) therapy. TT Virus DNA was detected by using polymerase chain reaction. The nucleotide sequences were determined by using a dideoxy chain termination method. A phylogenetic tree was drawn up by using the neighbor-joining method. RESULTS: TT Virus DNA was detected in 37.9% of patients with the use of an open reading frame 1 (ORF1) primer, and in 88.4% of patients by using a 5' untranslated region (5' UTR) primer. Using both sets of primers, no differences were found between TTV-DNA positive and -negative subjects with CHC in the clinical findings. Serum TTV DNA was eradicated in 30.6% of patients with the ORF1 primer, and in 19.1% of patients with the 5' UTR primer at 6 months after the cessation of IFN therapy. The levels of TTV DNA before IFN therapy were significantly lower in the viral eradication group than in non-eradication group. The changes in alanine aminotransferase (ALT) concentrations were significantly correlated with changes in HCV-RNA in CHC patients with TTV. Moreover, there was no correlation between the changes in TTV DNA and the course of ALT. CONCLUSION: Hepatocellular injury in patients with chronic hepatitis who are coinfected with HCV and TTV appears to primarily be caused by HCV and is less attributable to TTV. PMID- 11207903 TI - Comparison of clinical, virologic and pathologic features in patients with acute hepatitis B and C. AB - BACKGROUND AND AIMS: The clinical outcomes of adult-acquired acute infection of hepatitis C virus (HCV) and hepatitis B virus (HBV) are quite different. In order to compare the clinical, biochemical, virologic and pathologic pictures in these two groups of patients, we enrolled 22 adult patients with acute hepatitis C and 16 adult patients with acute hepatitis B, on whom liver biopsies were performed within 3 months of acute onset of the illness. RESULTS: The results showed that a significantly younger age, a higher ratio of the clinical symptoms of jaundice, nausea, vomiting, and poor appetite, a higher mean serum level of alanine transaminase, aspartate transaminase, and total bilirubin were present in patients with acute hepatitis B patients than in those with acute hepatitis C (P < 0.05). There was a significantly higher degree of periportal inflammation and total necro-inflammatory activity in the acute hepatitis B patients (P = 0.002 and 0.049, respectively). Fifteen (68.2%) of the 22 patients with acute hepatitis C had detectable serum HCV-RNA, but only two (14.3%) of the 14 tested patients with acute hepatitis B had detectable serum HBV-DNA, detected by using the branched DNA signal amplification assay. Eighteen (82%) of the 22 acute hepatitis C patients and none of the 16 acute hepatitis B patients progressed into a chronic hepatitis stage (P < 0.001). CONCLUSION: The manifestations of mild clinical symptoms, lower mean serum transaminases and bilirubin levels, a lesser degree of histological periportal necroinflammation, and more patients with a high circulatory viral load among the acute hepatitis C patients, may lead to more of that group developing chronicity than patients with acute hepatitis B. PMID- 11207904 TI - Prevalence of hepatitis B or C virus infections in patients with non-Hodgkin's lymphoma. AB - BACKGROUND: Hepatitis C virus (HCV) and hepatitis B virus (HBV) are not only hepatotropic, but also lymphotropic viruses. Recently, some reports suggested that these viruses may participate in the development of malignant lymphoproliferative disorders. METHODS: We investigated the prevalence of HCV or HBV infection in 348 patients with non-Hodgkin's lymphoma (NHL). We also compared these prevalences with those in blood donors as a control group representing the general population in our area (n= 1,513,358). Next, we evaluated the clinical and pathologic characteristics of HCV- or HBV-infected NHL cases. Non-Hodgkin's lymphoma was classified according to the Working Formulation classification. RESULTS: Thirty-seven cases (14.9%) were found to be infected with HCV or HBV; of these, 20 (8.1%) were infected with HCV, and 17 (6.9%) with HBV. In male NHL patients, the rate of HCV infection was significantly higher than in an age- and sex-matched population in the same area (P < 0.001, Mantel-Haenszel test). The rate of HBV infection also tended to be higher in the population (P = 0.0551). In contrast, in female NHL patients, the rate of HCV or HBV infection was not higher than in the general population. In HCV-infected cases, 15 cases (75%) had B-cell NHL and 16 cases (80%) were classified as being in the intermediate grade; B-cell NHL comprised 83% of all NHL cases. In HBV-infected NHL cases, 11 (65%) were of B cell type and 10 (58%) were classified as being in the intermediate grade. CONCLUSIONS: The high prevalence of HCV or HBV infections in our study population provides epidemiologic evidence suggesting that HCV and HBV infections may be involved in the development of a subgroup of NHL in males. Our investigation also revealed that both HCV- and HBV-infected NHL patients showed certain similarities in clinical and pathologic manifestations. PMID- 11207905 TI - Imaging and clinical characteristics of focal atrophy of segments 2 and 3 in primary sclerosing cholangitis. AB - BACKGROUND AND AIMS: Focal atrophy in primary sclerosing cholangitis (PSC) is usually thought to result from severe biliary stricture and focal biliary cirrhosis. Atrophy of the left lateral segments (segments 2 and 3) are striking when observed grossly. This type of atrophy may be subtle on cross-sectional imaging and by endoscopic retrograde cholangiopancreatography (ERCP) because of the peripheral location and compensatory hypertrophy of other parts of the liver. We examined 44 consecutive PSC patients to determine the incidence and clinical characteristics of this abnormality, and to correlate imaging studies with the gross appearance. METHODS: We reviewed all cases of PSC encountered over a 3 year period ascertained from the liver disease registry. Magnetic resonance imaging or CT images were re-examined for evidence of segment 2 and 3 atrophy. RESULTS: Four of 44 patients had focal segment 2 and 3 atrophy. These four had been confirmed laparoscopically or by inspection of the liver explant. The remaining segments of the liver were relatively spared of injury in two of the patients, and three of the four patients had preserved synthetic function without evidence of portal hypertension. While the abnormality is clearly visible on cross-sectional imaging, its peripheral location caused it to be an unobtrusive. Likewise, ERCP did not clearly reveal the abnormality on initial inspection. CONCLUSIONS: We conclude that focal atrophy of segments 2 and 3 is a sometimes early and subtle finding in PSC that may be overlooked in cross-sectional imaging or ERCP unless specifically sought. PMID- 11207906 TI - Images of interest. Hepatobiliary and pancreatic: an old woman with gallstones. PMID- 11207907 TI - Images of interest. Gastrointestinal: gastric volvulus. PMID- 11207908 TI - Hepatobiliary and pancreatic: Commentary. PMID- 11207909 TI - Sphincter of Oddi dysfunction associated with choledochal cyst. AB - The pathophysiology of choledochal cysts remains unclear, although an association with anomalous pancreato-biliary junction and the reflux of pancreatic enzymes into the biliary tree is known. Sphincter of Oddi (SO) manometry was performed in three patients with choledochal cysts. All patients exhibited an elevated basal pressure diagnostic of sphincter of Oddi dysfunction. Two patients exhibited anomalous pancreato-biliary junction. This report suggests an association between the choledochal cyst and sphincter of Oddi dysfunction, and may suggest that SO dysfunction plays a role in choledochal cyst formation. PMID- 11207910 TI - Duodenal tuberculosis with a choledocho-duodenal fistula. AB - A 22-year-old man visited our hospital (National Cancer Center Hospital East) complaining of fatigue and anorexia. A laboratory investigation demonstrated a biochemical 'picture' of obstructive jaundice. An abdominal CT showed a low density mass in the retropancreatic area with multiple enlarged periportal lymph nodes. Upper gastrointestinal endoscopy revealed active ulceration on the dorsal wall of the descending part of the duodenum, and histopathology of the biopsy specimen revealed an ulcer with reactive inflammatory cell infiltration; no tumor cells were detected. The possibility of neoplasm had been ruled out by the use of CT and angiography. The jaundice recovered spontaneously and the abdominal mass gradually decreased in size. Endoscopic retrograde pancreatography showed no evidence of pancreatic disease; however, endoscopic retrograde cholangiography showed a choledocho-duodenal fistula. This patient showed hypersensitivity against the tuberculin skin test and Mycobacterium tuberculosis was successfully detected in gastric juice by using a polymerase chain reaction method and culture. Biopsy samples obtained from the duodenal ulcer at the second upper gastrointestinal endoscopy showed chronic inflammation with an epithelioid granuloma, suggesting tuberculosis. We thus diagnosed this case as a duodenal tuberculosis with a choledocho-duodenal fistula. To the best of our knowledge, there has been no report available of duodenal tuberculosis being the cause of a choledocho-duodenal fistula. PMID- 11207912 TI - Editorial. PMID- 11207911 TI - Changes in titers of antimitochondrial and antinuclear antibodies during the course of primary biliary cirrhosis. AB - A case of primary biliary cirrhosis (PBC) in whom a complete biochemical (serum bilirubin, transaminases and alkaline phosphatase) remission was noted after combination treatment with ursodeoxycholic acid (UDCA) and corticosteroid is reported. The antimitochondrial antibody (AMA) detected by indirect immunofluorescence was initially positive, and the antinuclear antibody (ANA) was negative, but these two antibodies subsequently fluctuated independently (AMA positive/ANA-negative, AMA-negative/ANA-negative, AMA-negative/ANA-positive, AMA positive/ANA-positive, and again AMA-negative/ANA-positive) in spite of a lack of histopathological improvement in the liver after treatment. The clinical presentation in our case suggests that in some cases the diagnosis of PBC or so called autoimmune cholangitis (AIC) might depend on the 'phase' of the same disease. Our results also suggest that detailed immunoreactive profiles against 2 oxo-acid dehydrogenase complex (2-OADC) enzymes by using immunoblotting, together with a serial histological examination, should provide more precise information for a diagnosis of PBC. PMID- 11207913 TI - Polymer composites in 2000: structure, performance, cost and compromise. AB - Polymer matrix composites are based on the combination of stiff, strong reinforcing fibres with either thermosetting or thermoplastic polymer matrices. Since their introduction in the early 1940s, the world market has increased to some 5 million tonnes per annum, and some composites may now be considered commodity materials. The spectrum of fibre-reinforced plastics ranges from very high-performance speciality materials costing more than $1000/kg to these commodity composites, with more modest properties, at less than $10/kg. The performance of composites is determined by the properties of the fibre, the fraction of fibre in the composite and the structure, or fibre architecture. Processing technologies have been developed which maximise fibre content and precisely control the fibre architecture allowing for the manufacture of components with mechanical properties tailored to service requirements. Many composites offer significant advantages in specific stiffness and/or specific strength over metals. This makes them attractive for applications where high mechanical performance and minimum weight are important. However, the wider acceptance of composites is based on their ability to offer a more cost-effective alternative. In particular, composites also allow a dramatic reduction in the parts count in many applications, which leads to significant manufacturing advantages and greater economy. PMID- 11207914 TI - Active coatings for SiC particles to reduce the degradation by liquid aluminium during processing of aluminium matrix composites: study of interfacial reactions. AB - The application of a surface coating on SiC particles is studied as an alternative means of solving problems of reactivity between SiC reinforcements and molten aluminium and problems of low wetting which limit the application of casting routes for fabrication of Al-SiCp composites. The selected active barrier was a ceramic composed of SiO2, which was generated by controlled oxidation of the SiC particles. The coating behaves as an active barrier, preventing a direct reaction between molten aluminium and SiC to form Al4C3 as the main degradation product. At the same time, the SiO2 provokes other interfacial reactions, which are responsible for an improvement in wetting behaviour. Composites were prepared by mixing and compacting SiC particles with Al powders followed by melting in a vacuum furnace, and varying the residence time. Transmission electron microscopy (TEM), high resolution electron microscopy (HREM) and field emission TEM were employed as the main characterization techniques to study the interfacial reactions occurring between the barrier and the molten aluminium. These studies showed that the SiO2 coating behaves as an active barrier which reacts with the molten Al to form a glassy phase Al-Si-O. This compound underwent partial crystallization during the composite manufacture to form mullite. The formation of an outer crystalline layer, composed mainly of Al2O3, was also detected. Participation of other secondary interface reactions inside the active barrier was also identified by HREM techniques. PMID- 11207915 TI - Epitaxial nucleation of crystallization at polymer-filler interfaces. AB - In polymer composites the interaction between polymer matrix and filler particles often results in nucleation of spherulites. The principles of polymer crystal nucleation and spherulite growth are investigated using scanning transmission electron microscopy (STEM) and microdiffraction techniques in combination with polarized light microscopy. Simultaneous diffraction patterns from the interface of the filler and the polymer were obtained. Special precautions for successful recording of the diffraction patterns were used to overcome the rapid loss of polymer crystallinity, resulting from electron beam damage. Analysis of the diffraction patterns has shown that partial epitaxial correlation between the atomic periodicity of the particle surface and the molecular periodicity of polymer chains is always present when spherulites are nucleated. STEM images show that only large particles, with well developed facets (cleavage planes), are nucleating. The nucleating efficiency of the filler is therefore dependent on the size as well as on the crystallographic orientation of the facet. Small particles, or those with no suitable facets, do not affect the crystalline structure of the polymer. It is also shown that anisotropic polymer structures can be formed by inhomogeneous dispersion of nucleating filler particles. PMID- 11207916 TI - High-resolution electron microscope observation of interface microstructure of a cast Al-Mg-Si-Bi-Pb(6262)/Al2O3p composite. AB - High-resolution electron microscopy was employed to characterize the interface structure of a cast Al-Mg-Si-Bi-Pb aluminium(6262)-based composite reinforced by alpha alumina particles with a trace of beta alumina in order to investigate the behaviour of alloying elements in cast composites. Except for a few primary Mg2Si particles, few reaction products were detected at the interface of Al/alpha-Al2O3 due to the unfavourable reaction kinetics during the squeeze-casting process. The Mg2Si particle has an orientation relationship with alpha-Al2O3 of [011]Mg2Si//[1210]alpha-Al2O3 (111)Mg2Si//(0006)alpha-Al2O3. A significant amount of MgAl2O4 was found on the surface of the beta-Al2O3 particles, which is in contrast to the small degree of reaction found on alpha-Al2O3 particles. MgAl2O4 and beta-Al2O3 particles have the following orientation relationship: [011]MgAl2O4//[1210]beta-Al2O3 (111) MgAl2O4//(0006)beta-Al2O3. The similar crystal structure of beta-Al2O3 to MgAl2O4 favours MgAl2O4 nucleation and growth on the surface of beta-Al2O3. Interfacial energy minimization dominates the atomic structure of the interface with the result that close packed planes and directions in the Al2O3 reinforcement and reaction products are parallel to the interfaces. Bi and Pb were found in the form of metallic nanometre particles between Al2O3 particles, or between the MgAl2O4 and Al2O3 particles, or in the open channels of beta-Al2O3 filled by the Al matrix. PMID- 11207917 TI - Voronoi cells, fractal dimensions and fibre composites. AB - The use of fibre-reinforced polymer matrix composite materials is growing at a faster rate than the gross domestic product (GDP) in many countries. An improved understanding of their processing and mechanical behaviour would extend the potential applications of these materials. For unidirectional composites, it is predicted that localized absence of fibres is related to longitudinal compression failure. The use of woven reinforcements permits more effective manufacture than for unidirectional fibres. It has been demonstrated experimentally that compression strengths of woven composites are reduced when fibres are clustered. Summerscales predicted that clustering of fibres would increase the permeability of the reinforcement and hence expedite the processing of these materials. Commercial fabrics are available which employ this concept using flow-enhancing bound tows. The net effect of clustering fibres is to enhance processability whilst reducing the mechanical properties. The effects reported above were qualitative correlations. To improve the design tools for reinforcement fabrics we have sought to quantify the changes in the micro/meso-structure of woven reinforcement fabrics. Gross differences in the appearance of laminate sections are apparent for different weave styles. The use of automated image analysis is essential for the quantification of subtle changes in fabric architecture. This paper considers Voronoi tessellation and fractal dimensions for the quantification of the microstructures of woven fibre-reinforced composites. It reviews our studies in the last decade of the process-property-structure relationships for commercial and experimental fabric reinforcements in an attempt to resolve the processing vs. properties dilemma. A new flow-enhancement concept has been developed which has a reduced impact on laminate mechanical properties. PMID- 11207918 TI - Thermal imaging of composites. AB - Active thermal imaging techniques and their applications to composite materials are reviewed. The techniques included are transient thermography, scanning thermal microscopy and scanning thermal probe microscopy. The factors that affect the images produced by both pulsed and periodic forms of active heating are considered. For pulsed heating, experimental and numerical modelling results for carbon fibre-reinforced plastic are used to show how the resolution of subsurface features depends on their size and depth and on the anisotropy in thermal materials properties common in such composites. For periodic heating, thermal wave characteristics are introduced to show how the resolution of subsurface features also depends on modulation frequency and focal spot radius. Examples are given of the applications of scanning thermal microscopy and scanning thermal probe microscopy that illustrate the potential of these techniques for the imaging of composite materials. PMID- 11207919 TI - Localization of strain in metal matrix composites studied by a scanning electron microscope-based grating method. AB - The deformation characteristics of the metal matrix composites Ag/Ni and Al/Al2O3 are studied at microstructural level by a scanning electron microscopebased grating method and finite element (FE) simulation. The measured strain was found to localize in narrow bands in the ductile matrix of both composites. In the case of the Al/Al2O3 composite, the bands are preferentially initiated in Al regions adjacent to the interface of large Al2O3 particles, leading to local strain maxima. The band positions found in the Ag/Ni composite are also affected by the less deformable Ni phase, but strain localization first occurs by sliding of single Ag grains sometimes located away from the Ni phase. Using a FE model of real phase geometry and measured border displacements as boundary conditions, the simulation agrees reasonably with the experiment. The differences in the case of the Al/Al2O3 composite are due to particle cracks and voids at the particle/matrix interface. This effect was found in the experiment but not considered in modelling. For the Ag/Ni composite the band positions agree fairly well. However, the level and gradient of strain is clearly different as the crystallographic orientation of the Ag grains was not accounted for in modelling. PMID- 11207920 TI - Microstructural analysis of silicon carbide monofilaments. AB - In the development of monofilaments, a good understanding of the process/property relationships is essential. Transmission electron microscopy (TEM) is a powerful tool but too slow and expensive to be used routinely. Alternative, cheaper techniques have therefore been investigated. The microstructures of three SiC monofilaments (DERA Sigma SM1140+, Textron SCS-6 and Ultra-SCS) and some experimental samples were studied using a combination of TEM, electron microprobe analysis, Raman microprobe analysis, thermo-gravimetric analysis (TGA) and differential scanning calorimetry (DSC). It was found that the Raman technique was complementary to TEM and easily identified the presence of amorphous C and Si. These could not be seen by electron or X-ray diffraction techniques. DSC indicated the presence of free Si in the DERA Sigma SM1140+ monofilament by a distinctive peak at approximately 1400 degrees C. TGA showed the reaction of monofilament components with gaseous species. The Textron SCS-6 and Ultra species lost weight as C was oxidized to gaseous CO. By contrast, the Sigma monofilament gained weight from formation of SiO2 from the free Si. The separations of the transverse optical phonon peaks in the Raman spectra were correlated with the density of stacking faults in the SiC crystallites. This was similar in all monofilaments. Analysis of the polarization of the Raman scattering gave information on the orientation of crystallites. The crystallites in SM1140+ and SCS-6 were orientated predominantly with the <111> parallel to the radius. Preliminary interpretation of the polarized Raman scattering from Ultra-SCS indicated more than one orientation of crystallite. One possibility was a mixture of <111> and <110> directions parallel to the radius. PMID- 11207921 TI - Simulation and quantitative assessment of homogeneous and inhomogeneous particle distributions in particulate metal matrix composites. AB - Reinforcement distributions play an important role in various aspects of the processing and final mechanical behaviour of particulate metal matrix composites (PMMCs). Methods for quantifying spatial distribution in such materials are, however, poorly developed, particularly in relation to the range of particle size, shape and orientation that may be present in any one system. The present work investigates via computer simulations the influences of particle morphology, homogeneity and inhomogeneity on spatial distribution measurements obtained by finite-body tessellation. Distribution inhomogeneity was simulated both by the segregation of particles away from specified regions within a microstructure and by generating point density peaks at random locations within a microstructure. Both isotropic and anisotropic inhomogeneous distributions were considered to simulate distribution patterns in PMMCs before and after mechanical working. It was found that the coefficient of variation of the mean near-neighbour distance (COV(dmean)), derived from particle interfaces using finite-body tessellation, was essentially independent of particle shape, size distribution, orientation and area fraction in homogeneous (random) distributions, but showed great sensitivity to inhomogeneity. Increased values of COV(dmean) were seen for both forms of inhomogeneous distributions considered here, with little influence of particle morphology. The COV(dmean) was also seen to be sensitive to anisotropic clustering, the presence of which was identified via nearest-neighbour angles and cell orientations. Although generally formulated for PMMCs, the present results may be generalized to other systems containing low aspect ratio finite bodies of low to moderate area fraction. PMID- 11207922 TI - Microstructural analysis of a FeAl/quasicrystal-based composite prepared using a focused ion beam miller. AB - A composite consisting of a brittle multiphase matrix containing both an Al-based quasicrystalline phase (psi) and an ordered body centred cubic phase (beta) and a relatively ductile ordered body centred cubic intermetallic FeAl phase has been developed as an abrasive wear-resistant coating material. It is applied as a 500 um thick layer onto stainless steel substrates through plasma spray processing. The microstructure of such materials can be readily examined by optical and scanning electron microscopy, but the inherent difficulty of preparing transmission electron microscope (TEM) samples has inhibited higher resolution studies. However, the relatively recent development of the focused ion beam (FIB) miller as a tool in materials science provides a method ideal for the preparation of TEM specimens of these materials. In this study a coating consisting of a mixture of an Al-Cu-Fe based quasicrystal and FeAl+Cr was deposited on to a 304 stainless steel substrate. TEM specimens were prepared using a FIB and subjected to detailed microstructural characterization. The structure consisted of elongated bands of a FeAl phase about 100 nm in width and several micrometres in length, which enclosed more equiaxed regions about 1 um in diameter that consisted of fine mixtures of quasicrystal and two Al-Fe-Cu phases isostructurally related to FeAl. PMID- 11207923 TI - Subsurface deformation of machined Al2O3 and Al2O3/5vol%SiC nanocomposite. AB - Under machine grinding, material removal in monolithic Al2O3 is by intergranular fracture and grain pull-out. In comparison, under the same grinding conditions, an Al2O3/5%SiC nanocomposite undergoes significant surface grooving and intragranular fracture. The subsurface deformation mechanisms were investigated by cross-sectional transmission electron microscopy. For Al2O3, the residual deformation zone was localized very close to the surface in the first layer of grains, with dislocations occurring only within 1.5 um of the top surface and a high density of basal twins penetrating to a depth of one single grain. Cracks were present along grain boundaries or basal twin interfaces. For Al2O3/SiC nanocomposites, the main residual plastic deformation is observed to be dislocations activated to a depth of about 10 um (approx. 3-4 grains), with twinning rarely observed. Possible mechanisms by which the SiC particles influence the subsurface deformation and material removal modes are discussed. PMID- 11207924 TI - Applications of microscopy to the deformation and fracture of rubber-toughened polymers. AB - The principal mechanisms of inelastic deformation in rubber-toughened plastics, and in other similar multiphase polymers, are shear yielding and multiple crazing in the rigid matrix phase, and cavitation in the soft disperse phase. Microscopy has played a very important part in the identification and study of these mechanisms. However, no one technique has been predominant. Polarized-light microscopy is useful for observing crazing, and has proved to be the most effective method for studying shear yielding, whereas transmission electron microscopy has provided valuable insights into the cavitation behaviour of complex rubber particles. Scanning electron microscopy has made significant contributions in the study of all three micromechanisms. In some microscopy investigations, thin sections have been strained in situ on the microscope stage. In others, specimens have been deformed in the bulk state before being polished and etched, or stained and microtomed, or coated with a thin layer of metal, in preparation for examination in the microscope. The importance of combining microscopy with other, complementary methods for studying deformation micromechanics is emphasized, and two novel methods for detecting cavitation in multiphase polymers are discussed briefly. PMID- 11207925 TI - Microcracking mechanism in a SiCf-SiBC composite creep-tested in argon. AB - This paper addresses the creep behaviour of a woven SiCf-SiBC composite, tested in tension under a partial pressure of argon, between 1273 K and 1473 K. It appears that the creep strain begins from 1273 K and becomes larger at higher temperatures. Moreover, the shapes of the creep curves led to the assumption of the existence of two competing deformation mechanisms depending on the temperature domain. The creep mechanism involved is microcrack damage-creep. From higher resolution studies at higher scales (scanning electron microscopy, transmission electron microscopy (TEM) and high resolution electron microscopy (HREM)), many types of damage were observed, for example matrix microcracking, fibre/matrix debonding and fibre/matrix sliding. The observations via TEM and HREM enabled us to specify the existence or not of the classical creep mechanism of the constituents of the composite, and also to characterize the behaviour and the role of the different interfaces and especially of the pyrocarbon interphase. These multiscale observations will be discussed in order to highlight the creep damage mechanism as a function of temperature of the SiCf-SiBC composites. PMID- 11207926 TI - Microstructure, toughness and flexural strength of self-reinforced silicon nitride ceramics doped with yttrium oxide and ytterbium oxide. AB - Self-reinforced silicon nitride ceramics with additions of either yttrium oxide or ytterbium oxide have been investigated at room temperature after various processing heat treatments. Devitrification of the intergranular phase in these materials is very sensitive to the heat treatment used during processing and does not necessarily improve their strength and toughness. Hot-pressed ceramics without a subsequent devitrification heat treatment were the strongest. The ytterbium oxide-doped silicon nitride ceramics were consistently tougher, but less strong, than the yttrium oxide-doped silicon nitride ceramics. In all the ceramics examined, the fracture toughness showed evidence for R-curve behaviour. This was most significant in pressureless sintered ytterbium oxide-doped silicon nitride ceramics. A number of toughening mechanisms, including crack deflection, bridging, and fibre-like grain pull-out, were observed during microstructural analysis of the ceramics. In common with other silicon nitride-based ceramics, thin amorphous films were found at the grain boundaries in each of the ceramics examined. Arrays of dislocations left in the elongated silicon nitride grains after processing were found to belong to the {101;0}<0001> primary slip system. PMID- 11207927 TI - Structural studies of pulsed-laser deposited nanocomposite metal-oxide films. AB - Pulsed laser deposition in vacuum has been used to develop metal-oxide nanocomposite films with well controlled structural quality. Results for the copper-aluminium oxide (Cu:Al2O3) system are used to illustrate the main morphological and structural features of these films. High resolution transmission electron microscopy (TEM) analysis shows that the films consist of Cu nanocrystals with average dimensions that can be controlled between 2 nm and 10 nm embedded in an amorphous Al2O3 matrix. It is observed that the in-plane shape of the nanocrystals evolves from circular to elongated, and the number of nanocrystals per unit area decreases as their size increases. This evolution is explained in terms of nucleation at the substrate surface and coalescence during the later stages of growth. The thermal stability of the films has been studied by in situ TEM annealing and no transformation could be observed up to about 800 degrees C when partial crystallization of the Al2O3 starts. PMID- 11207928 TI - Subsurface nanoindentation deformation of Cu-Al multilayers mapped in 3D by focused ion beam microscopy. AB - A new technique for the three-dimensional analysis of subsurface damage of nanocomposites is presented. Cu-Al multilayers, grown epitaxially on (0001)Al2O3 single crystals by ultra high vacuum molecular beam epitaxy, have been deformed by nanoindentation. Systematic slicing and imaging of the deformed region by focused ion beam microscopy enables a 3D data set of the damaged region to be collected. From this 3D data set, profiles of the deformed sub-surface interfaces can be extracted. This enables the deformation of the individual layers, substrate and overall film thickness to be determined around the damage site. These 3D deformation maps have exciting implications for the analysis of mechanical deformation of nanocomposites on a sub-micrometre scale. PMID- 11207929 TI - Accumulation of in-vivo fatigue microdamage and its relation to biomechanical properties in ageing human cortical bone. AB - Bone matrix accumulates microdamage in the form of microcracks as a result of everyday cyclic loading activities. In two very recent studies, which used conventional histological stains and light microscopy techniques, the amount of this in-vivo microdamage in the cortices of long bones has been shown to increase with age. These articles have suggested that in-vivo microcracks may have an effect on the material properties of the tissue. However, a precise quantitative relationship between the number of microcracks and the mechanical properties of these same bones has not been produced before, and in particular the way the microcracks may affect the stiffness, the strength or possibly the toughness of the tissue. This article presents an examination of the in-vivo microdamage in human bones by the use of laser scanning confocal microscopy, which offers better discrimination and allows examination of the cracks in-situ. Quantification of in vivo fatigue microcracks was performed by counting the microcrack numerical density and surface density in specimens for which we have previously derived a full set of mechanical properties as a function of age. It is shown that bone microdamage relates more to the toughness (measured by three different measures) of ageing bone tissue than to its stiffness and strength. The result allows us (i) to re-evaluate the fragility of ageing human bone and put more emphasis on its energy-related resistance to fracture than perhaps on its stiffness or strength and also (ii) to understand more fully the causal relationship and interactions between microcracks and tissue toughness. PMID- 11207930 TI - Dynamic experimentation on the confocal laser scanning microscope: application to soft-solid, composite food materials. AB - Confocal laser scanning microscopy (CLSM) is used to follow the dynamic structural evolution of several phase-separated mixed biopolymer gel composites. Two protein/polysaccharide mixed gel systems were examined: gelatin/maltodextrin and gelatin/agarose. These materials exhibit 'emulsion-like' structures, with included spherical particles of one phase (i.e. polymer A) within a continuous matrix of the second (i.e. polymer B). Compositional control of these materials allows the phase order to be inverted (i.e. polymer B included and polymer A continuous), giving four basic variants for the present composites. Tension and compression mechanical tests were conducted dynamically on the CLSM, with crack/microstructure interactions investigated using a notched compact tension geometry. Gelatin/maltodextrin composites exhibit a 'pseudo-yielding' stress/strain response in both tension and compression, when the gelatin-rich phase is continuous, which was attributed to debonding of the particle/matrix interface. This behaviour is significantly less apparent for both the gelatin/agarose composites, and the maltodextrin continuous gelatin/maltodextrin composites, with these materials responding in a nominally linear elastic manner. Values of the interfacial fracture energy for selected compositions of the two biopolymer systems were determined by 90 degrees peel testing, where a gelatin layer was peeled from either a maltodextrin or agarose substrate. For biopolymer layers 'cast' together, a value of 0.2 +/- 0.2 J m-2 was obtained for the fracture energy of a gelatin/maltodextrin interface, while a significantly higher value of 6.5 +/- 0.2 J m-2 was determined for a gelatin/agarose interface. The interfacial fracture energy of the two mixed systems was also determined following an indirect elastomer composite debonding model. An interfacial fracture energy of approximately 0.25 J m-2 was determined using this approach for the gelatin continuous gelatin/maltodextrin composite, which compares favourably with the value calculated directly by peel testing (i.e. approximately 0.2 J m-2). A somewhat higher value was estimated for the gelatin continuous gelatin/agarose system (1.0-2.0 J m-2), using this model, although there are severe limitations to this approach for this mixed gel system. In the present case, it is believed that the differing mechanical response of the two mixed biopolymer systems, when the gelatin phase is continuous, arises from the order of magnitude difference in interfacial fracture energy. It is postulated that polymer interdiffusion may occur across the interface for the gelatin/agarose system, to a significantly greater extent than for interfaces between gelatin and maltodextrin, resulting in a higher interfacial fracture energy. PMID- 11207931 TI - Interfacial reaction and its influence on the mechanical properties of the ASZ short fibre-reinforced Al alloy composite. AB - The effect of interfacial reaction on the mechanical properties of the AC8A Al alloy reinforced with ASZ short fibres (ASZ/AC8A composite) was studied. In the ASZ/AC8A composite, the interfacial reaction was observed to proceed between the SiO2 binder layer and Mg of the matrix to form MgAl2O4 at the interface. Formation of MgAl2O4 was believed to enhance the interfacial bonding strength, resulting in the improved composite strength. However, the interfacial reaction in the ASZ/AC8A composite always took place at the expense of Mg in the matrix, resulting in the composite devoid of the Mg bearing precipitates such as Al2CuMg and Mg2Si. Interfacial reaction mechanisms were investigated for composites containing various Mg contents. The resultant mechanical properties of the composite were measured to determine the adequate amount of Mg within the composite. Microstructural changes of the composite were observed using transmission electron microscopy and differential scanning calorimetry to provide qualitative analyses on the experimental observations. PMID- 11207932 TI - Transmission electron microscopy studies of squeeze cast Al-AlN composites. AB - Aluminium-matrix composites containing approximately 45 vol.% AlN particles were fabricated by melt infiltration of aluminium into an AlN preform under a pressure up to 130 MPa. Three types of aluminium alloy (2024, 6060 and 5754) were used. The as-prepared composites were studied by light microscopy, scanning and transmission electron microscopies, and energy-dispersive X-ray spectroscopy. As a result of the melt infiltration process, the composites are very dense and the microstructure shows a homogeneous distribution of the reinforcement. The interfaces are clean with very little porosity. Composites with 2024 and 6060 matrices were carefully studied by transmission electron microscopy (TEM) and high resolution electron microscopy (HREM) after heat treatments. Dislocation density in the matrix of the reinforced material increases due to the difference in thermal expansion coefficients of aluminium alloys and AlN. This can induce an accelerated ageing response of the coherent and semicoherent precipitations of age-hardened matrices. This behaviour has been studied in the 2024 and 6060 composites by using microhardness measurements and TEM. Reactions between the AlN reinforcement and aluminium matrices (6060 and 5754) were observed and analysed by TEM. Matrices containing some of magnesium display a MgAl2O4 spinel formation at the AlN/matrix interface. The spinel formation is probably due to the reaction between magnesium of the matrix and the thin Al2O3 layer on the AlN surfaces. This reaction can affect the mechanical behaviour of the composite infiltrated with the 5754 matrix. This has been confirmed by overageing some samples at high temperatures (300 degrees C and 550 degrees C) for 10 days in order to emphasize the interfacial reactions. PMID- 11207933 TI - Reducing chemical vapour infiltration time for ceramic matrix composites. AB - Conventional routes to producing ceramic matrix composites (CMCs) require the use of high temperatures to sinter the individual ceramic particles of the matrix together. Sintering temperatures are typically much higher than the upper temperature limits of the fibres. This paper details preliminary work carried out on producing a CMC via chemical vapour infiltration (CVI), a process that involves lower processing temperatures, thus avoiding fibre degradation. The CVI process has been modified and supplemented in an attempt to reduce the CVI process time and to lower the cost of this typically expensive process. To this end microwave-enhanced CVI (MECVI) has been chosen, along with two alternative pre-infiltration steps: electrophoretic infiltration and vacuum bagging. The system under investigation is based on silicon carbide fibres within a silicon carbide matrix (SiCf/SiC). The results demonstrate that both approaches result in an enhanced initial density and a consequent significant reduction in the time required for the MECVI processing step. Dual energy X-ray absorptiometry was used as a non-destructive, density evaluation technique. Initial results indicate that the presence of the SiC powder in the pre-form changes the deposition profile during the MECVI process. PMID- 11207934 TI - Monitoring unidirectional carbon/carbon composite processing by light microscopy. AB - Unidirectional carbon/carbon composites were prepared using polyacrylonitrile based carbon fibres and a commercial coal-tar pitch. The preparation includes a three-sequential-step process: (i) prepreging, (ii) moulding/pressing, and (iii) carbonization to 1000 degrees C. The effect of the process parameters including pressure, mould characteristics, and temperature and duration of pressure application on the microstructure of composites was monitored by light microscopy. Results show that the application of a pressure of 1 MPa close to the temperature of pitch solidification produces lower porosity composites. This porosity is significantly reduced when the solidification of the pitch is tempered by the introduction of a soak time of 10 h at the temperature at which pressure is applied. PMID- 11207935 TI - Novel MMC microstructure with tailored distribution of the reinforcing phase. AB - Saffil short fibre agglomerates with diameters of 0.4 mm to 1 mm have been prepared using a tumbling technique. These were packed and infiltrated with molten 6061 Al alloy to make a metal matrix composite (MMC) with a novel microstructure in which the composite spheres are randomly distributed in the fibre-free aluminium matrix. In parallel, a commercial preform made of identical Saffil alumina short fibres and having the same fibre volume faction was used to prepare a conventional MMC by the same technique. Microstructural observation indicates that, within the composite spheres, the local volume fraction of fibre decreases from the outer layer to the centre region. The energy absorption during fracture was estimated by using a three point loading test on notched samples and was compared with that for conventional MMCs. Preliminary results suggest that this novel MMC possesses higher energy absorption capability and hence better damage tolerance. The fracture surfaces were examined by scanning electron microscopy in order to inform these experimental results. PMID- 11207936 TI - Photoresponsive Fischer 344 Rats are reproductively inhibited by melatonin and differ in 2-[125I] lodomelatonin binding from nonphotoresponsive Sprague-Dawley rats. AB - Many temperate-zone species use photoperiod as an environmental cue to regulate reproductive timing. Strains of laboratory rats differ in their responsiveness to photoperiod, with the Fischer 344 (F344) strain being the most responsive known. F344 rats and closely related strains that differ in photoresponsiveness may be useful models to study the mechanisms and genetic basis for photoresponsiveness. We tested two hypotheses: (i) that melatonin mediates photoresponsiveness in F344 rats, as is the case in all other mammals tested, and (ii) that the location, abundance, or affinity of melatonin receptors, as estimated by the amount and location of binding of the radioligand 2-[125I]-iodomelatonin (IMEL) in the brain, might cause variation in photoresponsiveness among rat strains. Melatonin injections 1 h before lights off in a stimulatory photoperiod (L14 : D10) induced reproductive inhibition and reduced weight gain in a manner similar to short days of L8 : D16, while injections of ethanolic saline vehicle did not. Interestingly, melatonin injections administered during an inhibitory photoperiod (L10 : D14) caused greater inhibition of both reproduction and weight gain than short photoperiod alone. Pinealectomized F344 rats implanted subcutaneously with melatonin in a silastic capsule did not differ in testis size or body weight from controls with blank implants. The brains and pars tuberalis of the pituitary from photoresponsive F344 rats and nonphotoresponsive Harlan Sprague-Dawley (HSD) rats were processed for autoradiography using IMEL. We found significantly higher specific IMEL binding in the anterior and posterior regions of the paraventricular nucleus of the thalamus (PVNt) and reuniens nucleus of the thalamus of F344 rats than in the same areas in HSD rats. There were no differences between strains in specific IMEL binding in the medial PVNt, anteroventral and anterodorsal nucleus of the thalamus, suprachiasmatic nucleus, or the pars tuberalis. These results indicate that melatonin mediates photoresponsiveness in F344 rats. In addition, they provide support for the hypothesis that F344 rats may be photoresponsive due to differences from other strains in the location, density, or affinity of melatonin receptors. PMID- 11207937 TI - Corticosteroid effects on serotonin responses in granule cells of the rat dentate gyrus. AB - Granule cells in the rat dentate gyrus contain mineralocorticoid and glucocorticoid receptors to which the adrenal hormone corticosterone binds with differential affinity. These cells also express various receptor-subtypes for serotonin (5-HT), including the 5-HT1A receptor which mediates a membrane hyperpolarization accompanied by a decrease in membrane resistance. Earlier studies have shown that removal of corticosterone by adrenalectomy, particularly in the dentate gyrus, results in enhanced expression of the 5-HT1A receptor mRNA and increased 5-HT1A receptor binding capacity. This was normalized by activation of mineralocorticoid receptors or concurrent activation of both receptor types. In the present, intracellular recording study in vitro, we examined if the altered levels of 5-HT1A receptor mRNA and protein are associated with changes in the response to 5-HT. We found that the hyperpolarization and resistance decrease induced in granule cells by a submaximal (10 microM) dose of 5-HT were unaltered 2-4 days after adrenalectomy, indicating a dissociation between corticosteroid actions on 5-HT1A receptor mRNA/protein levels and functional responses to 5-HT. Subsequent occupation of mineralocorticoid receptors in vitro significantly suppressed the 5-HT induced change in resistance, 1-4 h after steroid application. Compared to this, concurrent activation of glucocorticoid receptors led to large responses to 5-HT. This modulation by steroids was not observed with a higher dose of 5-HT (30 microM). The data suggest that with moderate amounts of 5-HT, corticosteroids affect the information flow through the dentate gyrus such that excitatory transmission is promoted with predominant mineralocorticoid receptor activation and attenuated with additional glucocorticoid receptor occupation. PMID- 11207938 TI - Neural circuits regulating pulsatile luteinizing hormone release in the female guinea-pig: opioid, adrenergic and serotonergic interactions. AB - We studied three neurotransmitters involved in the regulation of pulsatile luteinizing hormone (LH) release: opioid peptides, serotonin and norepinephrine, using the ovariectomized guinea-pig. This is an attractive animal model due to the regularity of its LH pulses, enabling any disruptions to be clearly ascertained. In all experiments, a specific agonist or antagonist was administered, either alone or serially to enable detection of interactions, and effects on mean LH concentrations, pulse amplitude and interpulse interval were determined by PULSAR analysis. In the ovariectomized guinea-pig, catecholamines are stimulatory (acting through the alpha1 and alpha2 but not beta receptors, unlike other species), opioids inhibitory and serotonin permissively stimulatory to pulsatile LH release. Stimulatory effects of the opiate antagonist were not blocked by pretreatment with an alpha1- or alpha2-adrenergic antagonist. Similarly, pretreatment with the opiate antagonist did not prevent the suppression of LH release by alpha1 and alpha2 antagonists. This suggests that, in the guinea-pig, effects of opiates and catecholamines on LH release are exerted by independent pathways to luteinizing hormone releasing hormone (LHRH) neurones. For the opiate-serotonin interactions, pretreatment with the serotonergic antagonist did not block the stimulatory effect of the opiate antagonist on LH release. However, pretreatment with the opiate agonist could not be overcome by the serotonergic agonist. This suggests that the effects of the serotonin system on LHRH release may be indirectly mediated by opioid neurones. Taken together, these studies demonstrate that the three neurotransmitter systems studied are critically involved in normal pulsatile LH release in the female guinea-pig, and demonstrate novel functional relationships between the opioid and the adrenergic and serotonergic systems. PMID- 11207939 TI - Evidence for direct involvement of beta-catenin in phorbol ester-induced neurite outgrowth in GT1-1 hypothalamic neurones. AB - Gonadotropin-releasing hormone (GnRH) is a pivotal neuroendocrine regulator controlling reproductive functions. However, the scattered distribution of GnRH neurones in the mammalian brain has hindered studies on the development and differentiation of GnRH neurones. In the present study, we used the immortalized GnRH-producing GT1-1 cells to examine whether activation of protein kinase C (PKC) pathway with 12-O-tetradecanoyl-13-acetate (TPA) induces morphological and functional differentiation of GnRH neurones. TPA induced neurite outgrowth and inhibited proliferation of GT1-1 cells that were specifically antagonized by cotreatment of PKC inhibitor, calphostin C. The functional significance of TPA induced differentiation of GT1-1 cells was manifested in part by the changes in the effects of gamma-aminobutyric acid (GABA) on intracellular Ca2+ levels. In untreated GT1-1 cells, activation of GABA-A receptor with 10 microM muscimol increased intracellular Ca2+ levels, whereas such stimulatory effects disappeared in GT1-1 cells bearing neurites. Accordingly, muscimol could not stimulate GnRH release in TPA-treated GT1-1 cells. To elucidate the molecular mechanism underlying TPA-induced neurite outgrowth, we performed differential display reverse transcription-polymerase chain reaction. Among several genes that are affected by TPA treatment, we found a significant induction of beta-catenin mRNA expression. Along with the rapid induction of beta-catenin protein levels, we observed that beta-catenin was reallocated from cell-cell adhesion sites to the growth cones within 3 h of TPA treatment. Transient transfection studies with green fluorescent protein as a reporter gene demonstrated that beta-catenin overexpression alone can promote neurite outgrowth in GT1-1 cells. Moreover, TPA was found to increase the transcription-activational roles of beta-catenin. Together, these data provide evidence that beta-catenin is involved in the TPA induced functional differentiation of immortalized GnRH neurones. PMID- 11207940 TI - Effects of chronic bromocriptine treatment on tyrosine hydroxylase (TH) mRNA expression, TH activity and median eminence dopamine concentrations in ageing rats. AB - The purpose of this study was to investigate the age-related changes in the responsiveness of tuberoinfundibular dopamine (TIDA) neurones to chronic hypoprolactinemia induced by treatment with bromocriptine, a dopamine receptor agonist. In one experiment, TIDA neuronal activity after acute hypoprolactinemia or exogenous prolactin was monitored by measuring tyrosine hydroxylase (TH) activity in the stalk median eminence of middle-aged cycling female rats (10-12 months), old constant oestrous rats (18-20 months) and old pseudopregnant rats (22-24 months). In another experiment, middle-aged cycling (10-12 months) rats were treated with bromocriptine for 6 or 12 months. TH activity was measured in the stalk median eminence, TH mRNA levels were measured in the arcuate nucleus and dopamine concentrations were measured in the arcuate nucleus and median eminence. Responsiveness of TIDA neurones to exogenous prolactin and to the withdrawal of bromocriptine in these rats was also tested. While the TIDA neurones in all three age groups responded to acute hypoprolactinemia by showing a reduction in TH activity, older rats failed to respond to exogenous prolactin administration. In contrast, chronic hypoprolactinemia for 12 months enabled the rats to retain TIDA neuronal responsiveness to exogenous prolactin. It also decreased TIDA neuronal function as measured by dopamine concentrations in the median eminence, TH activity in the stalk median eminence and TH mRNA in the arcuate nucleus of ageing rats. The restoration of the responsiveness of these neurones to prolactin stimulation in older rats demonstrates for the first time that hypoprolactinemia produced by chronic bromocriptine treatment indeed provides a neuroprotective effect on TIDA neurones. These results indicate that maintaining a low level of neuronal activity by lowering prolactin levels may be a contributing factor in retaining the plasticity of TIDA neurones. PMID- 11207941 TI - Increased synaptic input to gonadotropin releasing hormone cells in preoptic area grafts that support reproductive development in female hypogonadal mice. AB - Ultrastructural studies have established that gonadotropin releasing hormone (GnRH) neuronal cell bodies receive sparse synaptic input compared to other neuronal cell types. In the present studies, immunocytochemistry for the presynaptic marker synaptophysin, coupled with confocal microscopy, was employed to evaluate whether there was a difference in synaptic input to GnRH cells within preoptic area grafts (hypogonadal, HPG; preoptic area, POA) in hypogonadal female mice that did or did not show ovarian development. GnRH cells in HPG/POA mice with ovarian development exhibited significantly higher numbers of synaptophysin immunoreactive (syn-IR) appositions as compared with HPG/POA mice without ovarian development. This suggests that synaptic input to the grafted GnRH cells is important for the correction of reproductive functions in HPG/POA mice. Following mating, Fos immunoreactivity was present in several GnRH cells in HPG mice with successful POA grafts, indicating the establishment of neuronal projections conveying somatosensory information to the GnRH cells in these mice. The presence of a higher number of syn-IR appositions to GnRH cells in the successful grafts supports this hypothesis. PMID- 11207942 TI - Thyroid hormones regulate pituitary growth hormone secretagogue receptor gene expression. AB - Thyroid hormones regulate growth hormone (GH) secretion by actions both at the hypothalamus and at the pituitary gland. At the level of the pituitary, thyroid hormones increase GH and GH-releasing hormone receptor (GHRH-R) mRNA expression. To test if thyroid hormones might also regulate the pituitary expression of mRNA for the recently identified GH secretagogue (GHS) receptor, GHS-R, primary pituitary cell cultures from adult male rats were treated with triiodothyronine (T3) and GHS-R mRNA levels were assessed by reverse transcriptase-polymerase chain reaction. T3 increased pituitary GHS-R mRNA levels in a dose- and time dependent manner. The stimulatory action of T3 on GHS-R mRNA levels was also observed in the presence of the RNA synthesis inhibitor, actinomycin D, indicating that gene transcription is not required. Closer examination of the decay rates of GHS-R mRNA in the presence of actinomycin D revealed T3 extended the half-life of the GHS-R mRNA from 8 h (basal) to15 h, demonstrating that T3 increases GHS-R mRNA levels in vitro by increasing message stability. PMID- 11207943 TI - Agonist-mediated endocytosis of rat somatostatin receptor subtype 3 involves beta arrestin and clathrin coated vesicles. AB - Agonist-induced endocytosis of somatostatin receptors determines subsequent cellular responsiveness to peptide agonist and influences somatostatin receptor scintigraphy, a technique to image various tumours. We examined the internalization of sst3HSV, an epitope-tagged type 3 somatostatin receptor, in transfected rat neuroendocrine insulinoma cells. Stimulation of these cells with somatostatin induced trafficking of coexpressed enhanced green fluorescence protein/beta-arrestin1 fusion protein and sst3HSV to colocalize in the same endocytic vesicles. Coexpression of a dominant negative mutant of the arrestin fusion protein with the receptor blocked the internalization of sst3HSV. Stimulation with somatostatin also induced the transient translocation of alpha adaptin, a component of the adaptor protein complex 2, to the plasma membrane. alpha-adaptin and clathrin colocalized with the receptor. By electron microscopy, we observed internalized sst3 in clathrin coated pits, endosomes and at the limiting membrane of multivesicular bodies, a location typical for receptors being recycled. Concordantly, we observed sst3HSV colocalized with Rab11 in a perinuclear compartment which is likely to correspond to the pericentriolar recycling endosome. Thus, agonist-induced endocytosis of sst3 depends on its interaction with beta-arrestin, involves the adaptor protein complex 2 and proceeds via clathrin coated vesicles to the recycling compartment. PMID- 11207944 TI - Effect of superior cervical ganglionectomy on 24-h variations in hormone secretion from the anterior hypophysis and in hypothalamic monoamine turnover during the preclinical phase of Freund's adjuvant arthritis in rats. AB - The effect of superior cervical ganglionectomy (SCGx) on 24-h rhythms of circulating adrenocorticotropic hormone (ACTH), growth hormone (GH), prolactin and luteinizing hormone (LH) and of hypothalamic noradrenaline content and dopamine and serotonin turnover, was assessed in rats 3 days after administering Freund's complete adjuvant. In sham-operated rats, Freund's adjuvant injection increased serum ACTH without affecting its diurnal rhythmicity. SCGx, performed 10 days earlier, suppressed 24-h rhythmicity and augmented mean values of circulating ACTH. A depressive effect of immunization on GH release was found in both sham-operated and SCGx rats. GH concentrations did not exhibit diurnal rhythmicity and decreased after immunization. Time-of-day-related changes in serum prolactin were significant for all examined groups, except for SCGx immunized rats. Freund's adjuvant administration augmented prolactin secretion. Daily changes in serum LH concentration and a decrease after immunization were found in both sham-operated and SCGx rats. SCGx: (i) counteracted inhibition of daily variations of noradrenaline content in medial hypothalamus of Freund's adjuvant-injected rats; (ii) decreased anterior hypothalamic dopamine turnover and augmented it in the medial hypothalamus; (iii) lowered amplitude of serotonin turnover rhythm in medial hypothalamus. The data indicate that several early changes in levels and 24-h rhythms of circulating ACTH and prolactin, and in hypothalamic noradrenaline content and dopamine and serotonin turnover, were modified by a previous SCGx in Freund's adjuvant-injected rats. PMID- 11207945 TI - The in vitro role of tumour necrosis factor-alpha and interleukin-6 in the hypothalamic-pituitary gonadal axis. AB - The adipocyte derived hormone leptin has been implicated as an important nutritional signal to the reproductive system, but the role of other adipocyte related cytokines is not clear. Tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 are present in adipose tissue and released into the circulation where plasma levels correlate positively with body mass index and body fat mass. These cytokines could play a role in signalling nutritional status to the hypothalamic-pituitary-gonadal axis. We investigated the effects of TNF alpha and IL-6 on basal and luteinizing hormone releasing hormone (LHRH) stimulated luteineizing hormone (LH) release from cultured anterior pituitary cells, harvested from either proestrus female or male Wistar rats. We examined the effects of TNF-alpha and IL-6 on LHRH release from hypothalamic explants harvested from proestrus female and male rats in vitro. IL-6 significantly suppressed LHRH stimulated LH release from male dispersed pituitaries throughout the dose range, but did not influence basal LH release. IL-6 had no effect on basal or LHRH stimulated LH release in dispersed pituitaries from proestrus females. By contrast, TNF-alpha significantly suppressed LHRH stimulated LH release in dispersed pituitaries from proestrus female rats in a dose responsive manner, but did not influence basal LH release. TNF-alpha had no effect on basal or LHRH stimulated LH release in dispersed pituitaries from male rats. TNF-alpha and IL-6 had no effect on LHRH release from male hypothalamic explants in vitro. TNF-alpha and IL-6 had no effect on LHRH release from proestrus female hypothalamic explants in vitro. TNF-alpha and IL-6 have differential effects in dispersed pituitaries harvested from males and proestrus female rats. TNF-alpha and IL-6 may be important in mediating some of the nutritional effects on the reproductive axis by acting at the level of the anterior pituitary rather than the hypothalamus. PMID- 11207947 TI - Editorial. PMID- 11207946 TI - Progestin regulation of galanin and prolactin gene expression in oestrogen induced pituitary tumours. AB - Galanin is a peptide widely distributed in the hypothalamic-pituitary axis. In the female rat pituitary, galanin is mainly present in lactotrophs, where it regulates their secretion and proliferation. Galanin expression is increased in oestrogen-induced prolactinomas, and it has been proposed that oestrogen effects on lactotroph function and proliferation could be mediated by galanin. Previous studies from our laboratory demonstrated that the synthetic progestin levonorgestrel antagonizes pituitary tumorigenesis of rats given oestrogen, reducing the number of proliferating cells and increasing cell death by nonapoptotic mechanism(s). To elucidate the role of galanin in levonorgestrel effects on the tumours, we examined galanin and prolactin mRNA and peptide expression in prolactinomas of rats receiving the progestin. Levonorgestrel reduced the pituitary weight and serum prolactin concentrations in oestrogen treated rats. Galanin mRNA expression (determined by in situ hybridization), and the number of galanin expressing cells (determined by immunocytochemistry) were also reduced by the progestin in tumour-bearing rats. However, neither prolactin mRNA content, nor the number of prolactin-expressing cells, were modified by levonorgestrel treatment of oestrogen-receiving rats. The present study suggests that levonorgestrel controls pituitary growth by diminishing galanin expression. In contrast, changes in serum prolactin concentration seem to be more related to the reduction in tumour size, since the reduction in galanin expression was not large enough to regulate prolactin mRNA expression or the percentage of lactotrophs. PMID- 11207949 TI - The quality manager. AB - In the entire quality management jigsaw, no one piece is more important than an adequately trained and qualified quality manager. The terms quality co-ordinator and quality improvement officer do nothing to assist the understanding of this vital member of a hospital's staff. This paper describes the qualifications and role of a quality manager and emphasises that few such qualified quality managers exist in Australian hospitals. PMID- 11207948 TI - The effects of a seamless model of management on the quality of care for emergency department patients. AB - The aim of this study was to examine the effectiveness of the seamless model of management on the quality of care for emergency department (ED) patients. This was a pre- and postintervention study of comparing post intervention data with the baseline on several variables of interest. The intervention was the seamless model of ED management, designed and implemented as a response to the challenge of increasing work load at the ED. Information on patients' waiting times, critical care performance, patients' satisfaction and staff morale was collected at baseline and postintervention for comparison. The results indicated significant improvements on all outcome measures were found postintervention. The average waiting time reduced by 40%, from 92.1 to 55.3 min, as well as the time to craniotomy from 120 to 45 min for more severe patients. Complaints from patients were reduced by 80% and staff morale had improved with a 48% reduction in sick days and a 80% reduction in staff resignations. Ambulatory patients presenting to the department saw a 20% improvement in their waiting time. We report a successful restructuring process that used routinely collected clinical and administrative data to highlight problems. Using these data and through a systematic planning process, appropriate strategies for restructuring were developed by emergency staff in partnership with the hospital executive. Significant improvements in waiting time and patient care were clearly demonstrated. PMID- 11207950 TI - 'Quality is everyone's business' why this approach will not work in hospitals. AB - Implementing effective quality management in hospitals requires quite complex micromanagement systems. Health professionals, doctors and nurses do not have the time, skills and in many cases the interest to be responsible for these systems. To state the 'quality is everyone's business' is to use a platitude that seriously understates the difficulty of the exercise. PMID- 11207951 TI - Using clinical indicators to identify areas for quality improvement. AB - Clinical indicators (CI) are increasingly being used to assess the quality of health care being provided by physicians and hospitals. However, a standardised reporting format and a methodology to assess the utility of the CI data has not been developed. This paper provides the reporting format that has been developed for the clinical colleges. The results for four surgical indicators are used to illustrate how the CI data can determine the potential to improve the quality of care. Numerical estimates of the potential gains that could be made are calculated by: (i) determining the outcome if the current mean rate was shifted to the rate for the best 20% of hospitals and (ii) identifying units with unusual variation in rates and shifting their rate to the average. All four indicators reveal gains that could impact on health policy and clinical practice. PMID- 11207952 TI - Variance analysis in clinical pathways for total hip and knee joint arthroplasty. AB - Clinical pathways are being increasingly used for daily patient care. The pathways consist of a sequence of critical treatment events matched to the patient's recovery. Variance analysis identifies deviations from the pathway and can be used for quality improvement and clinical audit. The aim of this study is to analyse the variances from clinical pathways in two common elective orthopaedic operations. A prospective variance analysis was performed from the clinical pathways of all patients undergoing total hip and total knee arthroplasty over a 12 month period. Variances were categorised according to their source and then further divided into serious and non-serious variances. A total of 65 patients underwent total knee replacement during the study. Eleven serious variances were recorded in eight of these patients (12.3%) with a surprisingly high number of cardiac events. A total of 52 patients underwent total hip replacement with nine serious variances recorded in seven of these patients (13.5%). Clinical pathways can be used as a means of incorporating evidence-based medicine into clinical practice. Variance analysis of the pathways can be utilised as a process of quality control and to improve patient outcomes. Serious variances within this study were higher than anticipated. PMID- 11207953 TI - Pressure ulcer prevention and care: a survey of current practice. AB - The incidence and management of pressure ulcers in hospitalised patients is an ongoing concern for nurses. Efforts to prevent pressure ulcer development are plagued with inconsistencies and a general lack of best practice guidelines. Establishing current practice approaches to the assessment, prevention and management of pressure ulcers is a necessary first step in the implementation of evidence-based/best practice guidelines. Anecdotal evidence suggested a range of different approaches were being used in a Sydney metropolitan area health service (AHS) to assess patients to identify those at risk, to prevent pressure ulcers and to treat existing ulcers. A collaborative research project was undertaken to examine current practice and to explore the apparent clinical variance. It involved the distribution of a questionnaire to registered nurses working within the AHS (n = 2113) and a review of nursing policy documents in the various hospitals in the health service area. While the overall response rate was satisfactory (40%) many of the returned questionnaires were incomplete. Only 21% (n = 444) of the questionnaires were deemed suitable for analysis. The findings highlight a range of inconsistencies within and across nursing practice domains. Nurses generally do not use a tool to assess pressure ulcer risk potential, but rely on a range of practice procedures and risk indicators to determine risk potential of developing pressure ulcers. Repositioning patients is the most common approach used in an attempt to prevent the development of pressure ulcers, but additional measures are diverse. Most nurses seem to be familiar with modern wound dressings such as hydrocolloids, foams and alginates in the treatment of second and third stage ulceration. However, the care provided by some nurses reflects an adherence to outdated practices, including the use of water filled gloves, povidone iodine and gauze packing. PMID- 11207954 TI - Adjusting the balance in health-care quality. AB - In an increasingly informed society there has been a growing interest by consumers in evaluating the quality-of-care provided by their practitioners. This task is complicated by an asymmetry in the technical knowledge required to assess health-care quality between consumers and health providers. Recently attempts have been made to incorporate patient views into the assessment of quality to try and address this asymmetry. A number of quality initiatives have been developed to help provide consumers with markers of practitioner competency including professional training programmes and examinations, quality standards and quality assurance activities. International trends include federal funding for quality improvement activities within practices, and greater use of information technology to provide error warning systems for practitioners, to monitor practice patterns, and to promote better communication of information between health services. It is important in developing these new initiatives that 'symmetrical' approaches which capture consumers' views on quality are employed. PMID- 11207955 TI - Clinicians' perceptions of placing a fetal oximetry sensor. AB - The aim of this study was to determine clinicians' perceptions of placing a fetal oximetry sensor. A survey was developed seeking details of staff category, birth suite experience, previous sensor placement, ease of application and use of epidural analgesia. Following staff feedback, the survey was revised from asking clinicians to rate women's comfort during sensor placement, to a visual analogue scale (VAS) of the clinician's assessment of the women's pain during sensor placement. Survey validity was sought from experts during development and for specific questions using item-total correlation in this analysis. Ease of sensor placement (n = 131) was rated as good or excellent 71% of the time. Clinicians rated women's comfort during sensor placement as good or excellent in 90% of cases. Median pain VAS was 0 (range 0-7.5). Item-total correlations of survey questions were all significant. Fetal oximetry sensor placement was rated well by clinicians in this purpose-designed survey. PMID- 11207956 TI - Evidence-based surgery at ASERNIP-S. Can this improve quality in surgical practice? Australian Safety and Efficacy Register of New Interventional Procedures-Surgical. AB - The Australian Safety and Efficacy Register of New Interventional Procedures Surgical (ASERNIP-S) project has been established to form a register of new surgical procedures which have been assessed for their safety and efficacy. The ASERNIP-S project systematically reviews the evidence and produces recommendations on the future use of surgical procedures in clinical practice. Further data may be collected to provide information on the outcomes of procedures in use in Australia. Horizon Scanning of new and emerging techniques and technologies complements the ASERNIP-S process. This research identifies procedures that will impact on clinical practice in the near future. Dissemination of information from ASERNIP-S assessments, both locally and internationally, is important for quality improvement. The ultimate aim is for appropriate changes in practice to ensure the highest quality of Australian healthcare. PMID- 11207957 TI - Hip fracture treatments--what happens to patients from residential care? AB - Hip fractures are a growing problem and new models of care have been called for. However, patients from residential care are rarely considered in these discussions. Hip fracture is a common serious problem for older people in residential care with profound effects on subsequent mobility and quality-of life. There are no Australian data documenting differences in hospital treatments offered to patients from the community and residential care to inform discussions. In a prospective audit we describe the treatment and 4 month outcomes of patients with fractured hips who were admitted to Flinders Medical Centre in South Australia from the community and residential care between August 1998 and June 1999. Information was collected on prefracture health, types of surgical and rehabilitation treatments and dependency. Of the 215 older adults who were admitted during this time, 183 agreed to participate (119 from community and 64 from residential care). Surgical management of the fracture was not affected by admission accommodation. Those from residential care had short hospital stays, less rehabilitation and access to physiotherapy. Although 61% of those from residential care were classified as independently mobile prefracture, by 4 months this had declined to 32% of survivors. Strategies to improve outcomes in those from residential care include: early identification of those walking independently prefracture with assessment by rehabilitation teams. Inclusion of liaison with community therapists in the clinical pathway and in selected cases use of 'rehabilitation at home' services to provide physiotherapy services should be considered. PMID- 11207958 TI - A system for systems is required for quality health systems. AB - Improving quality of health-care requires a systematic approach at many different levels within a health system. The levels range from the interactions between individual patient-health provider to the international stage. The provision of care within and between each level needs to be systematically organised if the quality of our health-care is to improve. There is a need to develop a systematic approach to the multiple systems within health care. An organisational structure similar to the Cochrane Collaboration may provide the mechanism to better coordinate all our efforts to improve health-care quality. PMID- 11207959 TI - From health information to health action. PMID- 11207960 TI - Childhood lichen planus: a report of 23 cases. AB - Lichen planus (LP) in children is a rare entity. We report 23 cases of childhood LP seen over a period of 7 years. Ninety-six percent of the children were of Arab ancestry. There were 52% boys and 48% girls. Classic LP was the most common clinical variant (70%), followed by eruptive generalized LP (13%). A majority of the patients had mild, localized disease. Oral involvement was seen in 39% of patients. Topical steroids were the mainstay of treatment in most of the cases. Children with chronic and recurrent disease responded to dapsone therapy, whereas in those with eruptive and widespread disease, UVB phototherapy was found to be safe and effective. The present report highlights the salient clinical features, treatment, and course of LP in children in Kuwait compared to those reported in children of other countries as well as those of adults. PMID- 11207961 TI - Dysplastic nevi of the scalp and forehead in children. AB - To determine if there is a significant difference in the relative frequency and degree of atypia of sporadic dysplastic nevi from the scalp, face, and neck area in children as compared with nevi from the rest of the body, we reviewed 99 consecutive biopsy specimens of melanocytic nevi from the scalp, face, and neck areas in children less than 18 years of age and compared them with 95 consecutive cases of nevi from other areas of the body in children of the same age. Large numbers of the nevi biopsied from the scalp (13 of 31; 41.93%) and forehead (2 of 10; 20%) were dysplastic. The number of dysplastic nevi from the neck (1 of 58; 1.72%) was not assessed as very different from the incidence found in other regions of the body, where 7 dysplastic nevi (7.36%) from a total of 95 nevi were found. Of the 13 dysplastic nevi from the scalp, 9 showed minimal atypia and 4 showed moderate atypia. No nevi with severe atypia were found. Many pigmented nevi from the scalp and forehead in children in this study were dysplastic. This finding points out the importance of examining the scalp of children for the presence of dysplastic nevi. The majority of nevi from the neck were common nevi. PMID- 11207962 TI - Louse comb versus direct visual examination for the diagnosis of head louse infestations. AB - The techniques used for diagnosis of head louse (Pediculosis capitis) infestation are a source of controversy. Most epidemiologic and diagnostic studies have been done using direct visual examination. The main objective of this study is to compare the efficacy of direct visual examination versus the louse comb method. The hair of each child was examined twice; one team used a screening stick and another team used a louse comb. Seventy-nine boys and 201 girls, 7-10 years old were examined. Examination with a louse comb found that 25.4% of the children were infested with both lice and nits, while another 31.3% had nits only. Boys were significantly less infested with lice and nits than girls (lice: 15.2 and 29.6%; nits: 21.5 and 35.4%, respectively). The infestation rate with lice and nits was significantly higher in children with long (68.9%) and medium-length (63.9%) hair than in children with short hair (44.0%) (p < 0.01). Direct visual examination found that 5.7% of the children were infested with both lice and nits, and another 49.0% with nits only. The average time until detection of the first louse was 57.0 seconds with the comb as compared to 116.4 seconds by direct visual examination. Diagnosis of louse infestation using a louse comb is four times more efficient than direct visual examination and twice as fast. The direct visual examination technique underestimates active infestation and detects past, nonactive infestations. PMID- 11207963 TI - An ultrastructural study of lipodystrophia centrifugalis abdominalis infantilis, with special reference to fibrous long-spacing collagen. AB - Lipodystrophia centrifugalis abdominalis infantilis (LCAI) in a 2.5-year-old Japanese girl is reported. Clinically she had a curved cutaneous depression with a slightly elevated erythematous border on the left abdomen beyond the left groin. The regional lymph node was palpable. Histologic examination showed a decrease of the fat, an inflammatory infiltrate mainly composed of lymphocytes, and septal fibrosis in the subcutaneous tissue. Immunohistochemical analysis found that infiltrating lymphocytes were mainly positive against CD4. Ultrastructurally nuclei in the adipocytes were crescent shaped and located toward the periphery of the cell. Some banded structures with a periodicity of 150 nm, and with intraperiodic bands, referred to as fibrous long-spacing collagen (FLSC), were observed in the septal area of the fatty tissue. These results indicated that FLSC was correlated with the breakdown of fibrillar collagens in LCAI. PMID- 11207964 TI - Multiple familial smooth muscle hamartomas. AB - Smooth muscle hamartoma is a cutaneous abnormality characterized by a disorganized proliferation of normal muscle fibers of arrector pili. Usually a single congenital hypertrichotic plaque involves the trunk and the extremities. Multiple lesions have rarely been reported in the literature. We describe three members of the same family with multiple skin-colored patches on the back and legs, histologically confirmed as smooth muscle hamartomas. To our knowledge this is the first report of multiple smooth muscle hamartomas in different members of the same family and quite interestingly involving the same skin site. PMID- 11207965 TI - Lipoid proteinosis: report of four siblings and brief review of the literature. AB - Lipoid proteinosis (Urbach-Wiethe disease) is a rare autosomal recessive disorder associated with deposition of periodic acid-Schiff (PAS)-positive hyaline material in various tissues including skin, mucous membranes, and internal organs. A family is reported in which four siblings (two boys and two girls) born to nonconsanguineous parents had lipoid proteinosis. All had the characteristic hoarseness of voice and three had skin lesions. The diagnosis was confirmed by the presence of typical features on light and electron microscopy. PMID- 11207966 TI - Pseudopili annulati in a dark-haired individual: a light and electron microscopic study. AB - We report pseudopili annulati for the first time in a dark-haired Chinese girl. The hair was elliptical in shape and twisted along its long axis. The banded or ringed appearance was due to incident light being reflected by the flattened segments. Banding was also noted under polarized light but was not present under transmitted light. Under transmitted light the whole length of the hair appeared dark and the thickness varied at regular intervals, giving rise to fusiform segments due to the twisted nature of the hair shaft. Scanning and transmission electron microscopic examinations revealed no abnormalities in the cuticle and cortex. PMID- 11207967 TI - Periorbital congenital melanocytic nevus associated with ankyloblepharon. AB - We report periorbital congenital melanocytic nevus associated with ankyloblepharon in a 2-month-old boy. This unusual presentation may be explained by the assumption that the development of the congenital melanocytic nevus (CMN) in utero was related to the failure of normal eyelid separation, which occurs around the 20th week of gestation. PMID- 11207968 TI - Rubinstein-Taybi syndrome with epidermal nevus: a case report. AB - We describe an 8-year-old boy with Rubinstein-Taybi syndrome, a multiple congenital anomaly/mental retardation syndrome characterized by broad thumbs and great toes, peculiar facies, and mental retardation caused by mutations in the transcriptional coactivator CREB binding protein (CBP). He had on his right side yellowish papular lesions organized in narrow bands according to Blaschko lines, later confirmed by histology as an epidermal nevus. Epidermal nevus syndrome has been ruled out because the patient failed to meet the criteria for inclusion under this designation. This association may be coincidental. PMID- 11207969 TI - Toxic epidermal necrolysis after the use of high-dose cytosine arabinoside. AB - We report a fatal case of toxic epidermal necrolysis (TEN) resulting from a high dose of cytosine arabinoside (ARA-C). A 13-year-old girl with acute lymphocytic leukemia was treated according to the protocol of the BFM Group (BFM-95, HRG). On the fifth day after administration of a high dose of ARA-C (2 g/m2 intravenously every 12 hours), she developed bullous lesions on the hands and soles that disseminated, evolving to necrosis, sepsis, and death on the 22nd day. ARA-C is frequently associated with dermatologic toxicity, but this is only the second case of toxic epidermal necrolysis described in connection with this drug. PMID- 11207970 TI - Urticating Hashimoto-Pritzker Langerhans cell histiocytosis. AB - Red-brown papules developing during the neonatal period may present a diagnostic dilemma. The Darier sign has been a reliable feature in the diagnosis of mastocytosis. However, the cutaneous infiltrate of Hashimoto-Pritzker Langerhans cell histiocytosis (LCH) may contain a large number of mast cells, leading to confusion both clinically and histologically. We report an infant who developed red-brown papules of Hashimoto-Pritzker LCH during the neonatal period and presented with a positive Darier sign and acute urticaria. PMID- 11207971 TI - Papillon-Lefevre syndrome with pyogenic hepatic abscess: a rare association. AB - Papillon-Lefevre syndrome in a 14-year-old boy presenting with palmoplantar keratoderma, periodontosis, recurrent pyogenic infections of the skin, and hepatic abscesses is reported for its rarity and unusual manifestations. The patient showed a dramatic response to acitretin therapy. PMID- 11207972 TI - An unusual presentation of immunodeficiency with hyper-IgM. AB - Hyper-IgM syndrome is a rare immunodeficiency disease characterized by markedly decreased serum IgG, IgA, and IgE levels but normal or elevated IgM levels. The most common clinical signs are infections, cirrhosis, arthritis, malignancies, and mucosal ulcers. Approximately two-thirds of patients have chronic neutropenia associated with oral and perirectal ulcers. We report a 14-month-old girl with hyper-IgM syndrome who has recurrent cutaneous ulcers restricted to the diaper area. PMID- 11207974 TI - Incontinentia pigmenti: a case associated with cardiovascular anomalies. AB - Various cutaneous and developmental defects of the eyes, teeth, skeleton, and central nervous system have been detected in infants with incontinentia pigmenti. We report an isolated case of incontinentia pigmenti in a 6-month-old girl in association with tricuspid insufficiency, an abnormal shunt of the right pulmonary vein into the superior vena cava, and pulmonary hypertension. We believe that our findings will help to confirm the association of cardiovascular anomalies in IP. PMID- 11207973 TI - Complete recovery from juvenile pemphigus vulgaris. AB - A 10-year-old boy with vesicles and eroded lesions on his labia, oral mucosa, and trunk was diagnosed as having pemphigus vulgaris. The diagnosis was confirmed by histopathologic and immunofluorescence studies. The patient was successfully treated systemically with methylprednisolone and azathioprine. After 4.5 years the therapy was discontinued and the patient has had no relapse over the last 4 years. PMID- 11207975 TI - Localized acquired hypertrichosis following cast application. AB - A 11-year-old boy with transient hypertrichosis following calcaneal osteotomy and cast application for 2 months is described. We postulate that hyperemia may be responsible for his hypertrichosis, which lasted 3 months and created a cosmetic problem. PMID- 11207976 TI - Microsporum canis tinea capitis in an 8-month-old infant successfully treated with 2 weekly pulses of oral itraconazole. AB - We report an 8-month-old girl with tinea capitis caused by Microsporum canis which was successfully treated with two pulses of oral itraconazole 50 mg/day, each of 1 week duration with an interval of 2 weeks. M. canis tinea capitis can be a difficult therapeutic problem in an infant, as the treatment is usually long, lasting up to 4-6 weeks with griseofulvin and 6-12 weeks with terbinafine, and the desire to provide a safe systemic therapy is particularly important. With an intermittent regimen the duration of treatment with active drug can be much shorter compared to continuous therapy. We found that itraconazole pulse therapy for M. canis tinea capitis was a safe and effective treatment in an infant. PMID- 11207977 TI - Topical ivermectin: a new successful treatment for scabies. AB - Ivermectin is the only one of the avermectins that has been widely used in humans, since it is recommended as the treatment of choice for onchocerciasis, a filariasis that produces "river blindness," a parasitic endemic infestation in countries of West Equatorial Africa and in some areas of Central and South America. Also, ivermectin has been used for treating human endo- and ectoparasites with effective results and with almost no side effects. To study the efficacy of ivermectin for scabies, which is very common in Colombia, a trial with this drug that could be easily administered, with fast application and high efficacy, was undertaken. For this purpose, six complete families with active scabies, consisting of 12 adults and 20 children ranging in age from 1 to 10 years, were treated with 1% ivermectin in a solution of propylene glycol applied topically to the affected skin. The dose employed was 400 microg/kg, repeated once the following week. All patients were cured, tolerated the medication well, and there were no side effects or signs of recurrence 2, 4, or 6 weeks after therapy. In addition to its efficacy, easy administration, and lack of side effects, ivermectin is a low-cost medication. PMID- 11207979 TI - What syndrome is this? Chondroectodermal dysplasia--the Ellis-van Creveld syndrome. PMID- 11207978 TI - Allergic reactions due to ibuprofen in children. AB - Ibuprofen is 2-(4-isobutyl-fenyl)-propionic acid, which belongs to the same group of nonsteroidal antiinflammatory drugs (NSAIDs) as naproxen and ketoprofen. We present two instances of adverse reaction to pediatric ibuprofen, an acute urticaria and a fixed drug eruption, with tolerance to acetylsalicylic acid (ASA) and acetaminophen, in what seems to be hypersensitivity to the propionic acid group. Although these reactions are very rare and ibuprofen is still very safe, we think it is important to know about the possible side effects in order to recognize and treat them when they occur. PMID- 11207980 TI - Extensive hemorrhagic vesicles in a child. PMID- 11207981 TI - Scalp excisions: getting "ahead" of pain. PMID- 11207982 TI - Updated guide to information for families with inherited skin disorders. PMID- 11207983 TI - Inexpensive head lice comb. PMID- 11207984 TI - Myxoid liposarcoma in a 12-year-old girl: response. PMID- 11207986 TI - Neonatal herpes simplex and incontinentia pigmenti. PMID- 11207987 TI - Psoriasis in a 5-month-old girl with HIV infection. PMID- 11207988 TI - Eosinophilic cellulitis in a newborn. PMID- 11207989 TI - Mutation analysis of phenylketonuria in Yamagata prefecture, Japan. AB - BACKGROUND: We have screened 309,914 newborns in Yamagata prefecture, Japan, since 1977 and have detected four patients with phenylketonuria (PKU). We analyzed the phenylalanine hydroxylase (PAH) gene of the four patients to study the genetic background in this area and the genotype-phenotype relationship in these patients. METHODS: Mutations of the PAH gene were screened by denaturing gradient gel electrophoresis analysis and the sequences were determined. RESULTS: Three cases were compound heterozygotes of six different mutations of the PAH gene and the remaining case was a homozygote. Of the six detected mutations, K115fs is novel, whereas the others have been previously detected among Chinese and/or Japanese patients. CONCLUSIONS: The incidence and genetic basis in Yamagata prefecture was similar to that of other parts of Japan. Analysis of the genotype is useful to understand the clinical variation in some families. PMID- 11207990 TI - Epidemiology of Helicobacter pylori infection in children: a serologic study of the Kyushu region in Japan. AB - BACKGROUND: The prevalence of Helicobacter pylori infection in children varies as a function of socioeconomic development, with low rates in developed countries and high rates in developing countries. The prevalence of H. pylori infection in Japanese children is unknown. METHODS: The present study examined the effect of living conditions on the prevalence of H. pylori infection in children. We determined the prevalence of H. pylori infection in healthy children of the Kyushu region in Japan and compared it with the prevalence in institutionalized children with severe neurologic illness. Serum concentrations of anti-H. pylori IgG antibody were measured by an enzyme-linked immunosorbent assay in 336 healthy children and 56 patients with severe neurologic impairment. An antibody concentration > 50 units/mL was taken as evidence of infection. RESULTS: The prevalence of H. pylori seropositivity in healthy children increased with age (P < 0.0001) and was 29% in children 15-19 years of age. This value is slightly higher than prevalences reported in developed countries (5-15%), but is lower than in developing countries (30-60%). Seropositivity did not vary with respect to gender, water supply or location of housing. Helicobacter pylori seropositivity was more prevalent among institutionalized children aged 5-19 years than their healthy counterparts (P < 0.005). CONCLUSIONS: The intermediate prevalence of H. pylori seropositivity in healthy children between that measured in developed and developing countries is consistent with the socioeconomic 'westernization' of Japan. PMID- 11207991 TI - Effects of albumin infusion therapy on total and unbound bilirubin values in term infants with intensive phototherapy. AB - BACKGROUND: The purpose of the present study was to evaluate the effect of intravenous albumin administration on the serum total and unbound bilirubin values in term non-hemolytic hyperbilirubinemic neonates during intensive phototherapy. METHODS: Fifty-eight infants (gestational age 39.4 +/- 1.4 weeks; birth weight 3,245 +/- 435 g) were given phototherapy with similar light energy. Twenty infants (control group) received only phototherapy, while 38 others (albumin-treated group) were also given human albumin at 1 g/kg bodyweight, i.v., during the first 2 h of phototherapy. RESULTS: When comparing changes in total and unbound bilirubin values 0, 2, 6 and 24 h after entering the study between the albumin-treated group and the control group, there was a significant reduction in the serum unbound bilirubin values at the end of albumin treatment and at 6 and 24 h. However, there was no significant reduction in total serum bilirubin values during the study period. In the albumin-treated group, the mean serum unbound bilirubin reduction from the baseline level at the end of albumin treatment and at 6 and 24 h was 0.40 +/- 0.19, 0.41 +/- 0.20 and 0.43 +/- 0.20 microg/dL, respectively. CONCLUSIONS: The results suggest that albumin priming may be effective for an immediate reduction in serum unbound bilirubin values, the fraction that is potentially neurotoxic. PMID- 11207992 TI - Differences in transcutaneous bilirubin readings in Japanese term infants according to feeding method. AB - BACKGROUND: Controversy has existed for many years over whether infant feeding methods are related to serum bilirubin concentrations during the first few days of life. Differences in initial jaundice patterns according to the feeding method until 72 h after birth have not been elucidated hitherto. The difference may become clear in Japanese neonates because jaundice shows a much higher peak bilirubin concentration and a later peak in Japanese neonates than in Caucasian neonates. METHODS: In the present study, we investigated variations in the transcutaneous bilirubin reading (TcB) obtained within 72 h after birth among 177 breast-fed and 494 formula-fed healthy Japanese term neonates. RESULTS: There was no difference between TcB in formula-fed and breast-fed infants until the first 30 h, after which time the rate of increase in TcB was lower in formula-fed infants. Among breast-fed neonates, a good linear regression between time after birth and TcB was maintained. Similarly, weight losses in breast-fed infants at 24-48 h and 48-72 h after birth were greater than those in formula-fed infants. CONCLUSIONS: The jaundice pattern in Japanese neonates from 30 to 72 h after birth according to the feeding method was different from that in Caucasian neonates. PMID- 11207993 TI - Effect of vibration on auditory organ systems in low-birth weight infants treated with high-frequency oscillatory ventilation: 5 year outcome. AB - BACKGROUND: To determine the effects of vibration exposure caused by high frequency oscillatory ventilation (HFOV) on the auditory organ systems in low birth weight (LBW) infants. METHODS: Between 1989 and 1990, 30 LBW infants who received assisted ventilation with HFOV (n = 14) or conventional mechanical ventilation (CMV; n = 16) in the level III neonatal intensive care unit at Tokyo Metropolitan Ohtsuka Hospital were enrolled in this study. The effects of vibration exposure on the auditory system structures were investigated with auditory brainstem responses (ABR) at 37-41 weeks of postconceptional age and at 6, 12, 18 and 24 months of age until they passed and follow-up studies were performed at least until 5 years of age. RESULTS: All infants enrolled in the study survived at discharge and one (7.1%) infant in the HFOV group and two (12.5%) in the CMV group failed the initial ABR test, but there were no significant differences between the two groups. Auditory brainstem response abnormalities were still observed in one infant in the HFOV group at 6 months of age, but this child died at 9 months of age because of meningitis. In contrast, in the CMV group, one patient passed the ABR test at 6 months of age, but another remained abnormal at 5 years of age. One of three infants with ABR abnormalities at 6 months of age had neurologic sequelae at 5 years of age and one of 28 infants who passed the initial ABR test was detected with cerebral palsy. No patients with hearing loss were clinically detected at 5 years of age. CONCLUSIONS: The results of the serial ABR examinations and the 5 year follow-up studies suggest that vibration exposure caused by HFOV may not increase the adverse effects on the auditory system in LBW infants. PMID- 11207994 TI - A prospective clinical study on inhaled nitric oxide therapy for neonates in Japan. AB - BACKGROUND: This is the first report about a prospective clinical investigation to study the efficacy and safety of nitric oxide (NO) inhalation in infants with persistent pulmonary hypertension of the newborn (PPHN) in Japan. METHODS: Patients in the present study had to meet the following entry criteria: (i) they had to be younger than 7 days of age; (ii) they had to have evidence of PPHN as defined by echocardiograph; (iii) they had to have severe systemic hypoxemia under mechanical ventilation at 100% oxygen supplementation; and (iv) they had to have a failure to respond to conventional therapies. Patients were excluded from this trial if they had any of the following: hypoplastic lung, structural cardiac lesions or severe multiple anomalies. RESULTS: Nitric oxide inhalation therapy was performed in 68 infants who had severe PPHN at 18 hospitals between May 1995 and May 1997. At birth, 21 of 68 infants (31%) weighed less than 1,500 g and 39 infants weighed more than 2,500 g. The diagnoses associated with PPHN were as follows: 27 infants had meconium aspiration syndrome, 15 infants had dry lung syndrome, nine infants had congenital diaphragmatic hernia, six infants had respiratory distress syndrome, three infants had pneumonia and eight infants had other diagnoses. The mean oxygenation index (OI) before NO inhalation therapy in 68 infants was 43.2; 55 infants (81%) had good responses. CONCLUSIONS: These results may be valuable for further randomized controlled and double-blind trials in Japan to evaluate whether NO inhalation therapy is more effective than conventional therapy in infants with severe PPHN. PMID- 11207995 TI - Effect of gestational age on plasma fibronectin concentrations in the neonate. AB - BACKGROUND: Fibronectin (FN) is known to have important roles in host defense against infection. The risk for neonatal sepsis increases with the degree of immaturity of the host. Conflicting results have been reported on the relationship between plasma FN levels and gestational age (GA) in the preterm neonate. METHODS: In the present study, we determined plasma FN concentrations with an immunodiffusion method in 40 newborns of various gestational ages, ranging from 30 to 42 weeks. RESULTS: We found a strong direct correlation between plasma FN levels and GA (r = 0.86; P < 0.001). CONCLUSIONS: We speculate that the increased risk for neonatal sepsis with degree of prematurity may, in part, be explained by impaired defense with decreasing plasma FN levels seen with lessening GA. PMID- 11207996 TI - Contact pressure distribution in the supine position in low-birth weight infants analyzed by a photoelastic method. AB - BACKGROUND: Contact pressure distribution patterns in the supine position in low birth weight (LBW) neonates were analyzed by the use of a photoelastic method. METHODS: A total of 61 subjects (LBW neonates, mature (bodyweight > 2,500 g at birth) neonates, normal infants and Down syndrome (DS) infants) were selected for the study. Infants were placed on a photoelastic measuring table. Photoelastic images generated in the contact regions of the body were photographed with a camera and printed on monochrome paper. The coefficient of variation in the pressure distribution value (PcV) and the top and bottom ratio (mu) of the trunk at the center of pressure were calculated. RESULTS: The Pcv value was significantly lower in DS than LBW (P < 0.001), mature (P < 0.002) and normal infants (P < 0.01). The mu value in LBW and mature neonates was 48.9 and 50.2%, respectively. Normal infants had a mu value of 44.0%, which was significantly lower than that in LBW neonates. However, there was no significant difference between LBW and DS infants. CONCLUSIONS: Neurological impairment specifically affects the data obtained by photoelastic analysis. PMID- 11207997 TI - Risk factors for persistence of pulmonary arterial branch stenosis in neonates and young infants. AB - BACKGROUND: Pulmonary arterial branch stenosis (PBS) in neonates is considered to be transient. However, PBS has been found not only in neonates, but also in young infants. Among these patients, we encountered several patients whose PBS was still present after the age of 1 year. METHODS: To clarify the natural history of PBS in neonates and young infants, we retrospectively reviewed the records of 103 patients diagnosed with PBS in the neonatal period and early infancy. RESULTS: The PBS findings were improved in all patients. Pulmonary arterial branch stenosis disappeared in 94 patients by the age of 1 year (group A), but persisted after I year of age in nine patients (group B). Group B patients had a significantly lower mean birth weight and greater deltavelocity (the difference in the peak flow velocity between the main pulmonary artery and stenotic branch) at diagnosis than group A patients. Incidences of low birth weight (< 2,500 g) and deltavelocity above 1.2 m/s were significantly higher in group B than group A patients. There was no significant difference in the frequency of premature infants (gestational age < 36 weeks) between the groups, suggesting that intrauterine growth retardation may be related to developmental abnormalities of the pulmonary arterial branch. CONCLUSIONS: All cases of PBS in neonates and young infants were improved. However, PBS persisted in some patients after the age of 1 year. Low birth weight and deltavelocity above 1.2 m/s are risk factors for persistent PBS. Pulmonary arterial branch stenosis was not present after the age of 1 year in 62 of 63 patients without either of these risk factors. PMID- 11207998 TI - Idiopathic sustained left ventricular tachycardia in pediatric patients. AB - BACKGROUND: Idiopathic sustained ventricular tachycardia originating from the left ventricle (ILVT) has been an indication for catheter ablation. The present study evaluated the clinical features, long-term prognosis and indications for treatment in pediatric patients with ILVT. METHODS: The subjects of the present study were eight patients (four males and four females) with a mean age at onset of 11.0 years (range 3-15 years). The mean follow-up period was 7.7 years (range 2.1-11.3 years). RESULTS: In electrophysiologic studies, intravenously administered verapamil was effective for the termination of tachycardia in all six patients who received this treatment and for the prevention of tachycardia in four of five patients. Oral administration of verapamil was effective in five of seven patients. Propranolol or flecainide was added to the treatment protocol for two patients who did not respond to verapamil alone. Tachycardia disappeared without drugs in four patients during the follow-up period and became non sustained in another patient. Two of three patients with persistent tachycardia underwent catheter ablation. Pharmacologic treatment was very effective for ILVT among these patients. CONCLUSIONS: Pharmacologic therapy, such as with verapamil, is still the treatment of choice for ILVT because of a good long-term prognosis and potential risks and complications by manipulation of catheter ablation. PMID- 11207999 TI - Anti-interleukin-8 autoantibody in the tracheobronchial aspirate of infants with chronic lung disease. AB - BACKGROUND: A high concentration of interleukin (IL)-8 has been observed in the tracheobronchial aspirate of infants with chronic lung disease (CLD), although the pattern varies depending on the type of CLD. Alveolar fluid from patients with adult respiratory distress syndrome (ARDS) also contains an elevated level of IL-8. Recently, the presence of anti-IL-8 autoantibody was demonstrated in the alveolar fluid from patients with ARDS. METHODS AND RESULTS: The concentration of anti-IL-8 autoantibody in the tracheobronchial aspirate of infants with CLD was measured in order to discover whether there was any correlation with the concentration of IL-8. Similar to IL-8 concentration, the anti-IL-8 IgM antibody concentration in all infants with CLD following intrauterine infection was already high during the first 48 h. However, the concentration in infants with CLD following respiratory distress syndrome began to increase after 11 days of life, in contrast with the rise in IL-8 between 48 h after birth and day 5. CONCLUSIONS: The presence of anti-IL-8 autoantibody may provide a mechanism that limits the bioavailability of free IL-8 in the lungs. In addition, the time lag between the increase in IL-8 and anti-IL-8 IgM autoantibody demonstrated in the present study could be used to estimate the time when the inflammation begins, even if the IL-8 concentration is already high. PMID- 11208000 TI - Severe upper airway obstruction in the tropics requiring intensive care. AB - BACKGROUND: The clinical profile of severe upper airway obstruction, a challenging acute pediatric emergency, has not been extensively documented in the developing nations of the tropics. METHODS: The diagnostic categories, severity of illness and outcome from 63 episodes of severe upper airway obstruction in 56 children admitted to the Pediatric Intensive Care Unit between January 1994 and December 1999 were reviewed. Outcome variables studied included requirement for ventilation, mortality and complications. Severity of illness was determined with the Pediatric Risk of Mortality (PRISM) II score. RESULTS: Viral croup (29%) was the most common diagnosis, followed by mediastinal malignancy (13%), bacterial tracheitis (11%) and Pierre Robin syndrome (11%). There were no admissions for acute epiglottitis. Thirty episodes (48%) required ventilation for a median duration of 4.0 days. Bacterial tracheitis (100%) and subglottic stenosis (100%) were the most likely diagnoses requiring ventilation. Difficulty in intubation was encountered in 13 episodes (43%) involving, in particular, patients with bacterial tracheitis (83%; P = 0.006). Only two patients required a tracheostomy. The overall mortality was 11%. The PRISM score for all categories was generally low (mean 10.3 +/- 1.0; median 9.0). Non-survivors had a significantly higher PRISM II score than survivors (27.4 +/- 9.7 vs 8.1 +/- 4.9, respectively; P = 0.002) and were more likely to include children with bacterial tracheitis and mediastinal malignancy. CONCLUSIONS: There is marked heterogeneity in the causes of upper airway obstruction in the tropics with viral croup remaining the most common. A significant proportion required ventilation, but outcome is generally favorable, except in those with bacterial tracheitis and mediastinal malignancy. PMID- 11208001 TI - Immunoglobulin subgroups in children with febrile seizures. AB - BACKGROUND: The aim of the present study was to determine whether or not there was a role for immunoglobulin (Ig) or IgG subgroups in the pathogenesis of febrile seizures (FS). METHODS: Serum levels of IgA, total IgG, IgM, IgE, IgGI, IgG2, IgG3 and IgG4 were measured in 34 children with FS and in 37 healthy children used as a control group. Both patients and controls were divided into two groups according to age (group I, 6-24 months; group II, 25-72 months). RESULTS: Compared with controls, mean IgG4 levels in patients were found to be decreased in both groups I and II (group I: 95 +/- 14 vs 57 +/- 5, respectively, P = 0.01; group II: 178.5 +/- 38.5 vs 65.1 +/- 24.5, respectively, P < 0.01), while mean IgG2 levels were found to be decreased only in group II patients (170 +/- 16 vs 103 +/- 22; P < 0.05). CONCLUSIONS: The results of the present study suggest that Ig subclass deficiencies may be responsible for the infections connected with FS or that they may be related to the pathogenesis of FS in some children. PMID- 11208002 TI - Vagus nerve stimulation for children and adolescents with intractable epilepsies. AB - BACKGROUND: Vagus nerve stimulation (VNS) has been shown to be efficacious in the treatment of patients > 12 years of age with refractory partial epilepsies and it is suggested that VNS should be considered as one of the treatment options for these patients. METHODS: Four patients had partial epilepsies and one had symptomatic generalized epilepsy. After observation of the baseline seizure frequency and the average seizure frequency for 3 months, the VNS system was implanted. Thereafter, seizure frequency, average seizure frequency of each seizure type during the month just before the evaluation, seizure severity, side effects and quality of life were recorded. RESULTS: In four of five patients, overall seizure frequency was reduced > 50% after VNS treatment. The seizure types that showed a > 50% reduction in frequency were auras, focal clonic, generalized tonic clonic seizures, astatic, versive, hypomotor, generalized tonic and generalized clonic seizures according to Luders' classification. In two patients, as major convulsive seizures were reduced in number after VNS treatment, dialeptic seizures (non-convulsive seizure with lapse of consciousness) gradually appeared. In one patient without significant seizure reduction, quick recovery from postictal periods after generalized tonic seizure was seen after treatment. In one patient with generalized epilepsy, improvement of cognitive function was reported by his guardians. After VNS, the number of antiepileptic drugs was reduced from three to one in one patient. No significant adverse effects were noted in any patients. CONCLUSIONS: Our results suggest that VNS is well tolerated in young patients with intractable epilepsies and it may be an important non-pharmacologic treatment option for children with severe epilepsies who cannot tolerate medical therapy and/or are not candidates for epilepsy surgery. PMID- 11208003 TI - Cerebral blood flow abnormalities in symptomatic West syndrome: a single photon emission computed tomography study. AB - BACKGROUND: Infantile spasm (IS) is an age-dependent epileptic encephalopathy of variable etiology. Although IS is well studied, its pathogenesis is unclear. Infantile spasm is usually considered a generalized epilepsy, but recent studies point to focal cerebral blood flow (CBF) abnormalities. METHODS: In six symptomatic IS patients, single photon emission computed tomography (SPECT) with [99Tc]-HMPAO, electroencephalography (EEG), magnetic resonance imaging (MRI)/computed tomography (CT) and their correlation were evaluated. RESULTS: Single photon emission computed tomography showed unifocal (regional) cerebral hypoperfusion in two infants, multifocal (diffuse) cerebral hypoperfusion in three infants and normal perfusion in the other infant. Electroencephalograms obtained in near-time of the SPECT studies showed diffuse abnormalities in five infants with hypoperfusion on SPECT. Cranial MRI/CT showed diffuse and/or localized cerebral lesions in all infants, all of whom had corresponding areas of hypoperfusion on SPECT. In one patient whose spasms were stopped with anticonvulsants, SPECT was normal, in two patients SPECT showed unifocal lesions, while in another three patients whose spasms were decreased but not stopped, SPECT showed multifocal hypoperfusion. CONCLUSIONS: This pilot study may indicate that there are CBF anomalies in symptomatic IS. The degree of CBF may be a predictor of prognosis and multifocal hypoperfusion may be a poor prognostic criteria in IS. PMID- 11208005 TI - Possible effects of antioxidant status on increased platelet aggregation in childhood iron-deficiency anemia. AB - BACKGROUND: Alterations in platelet function and antioxidant status in children with iron-deficiency anemia (IDA) have been reported previously. The present study was performed to better understand possible interactions between these two systems. METHODS: Erythrocyte superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activity and platelet function were evaluated in 15 children (aged 1 1/2-15 years) with IDA. The antioxidant enzyme activity was determined spectrophotometrically. Platelet aggregation and secretion studies were performed using impedance and bioluminescence methods, respectively. Ten age matched healthy children were included as a control group. RESULTS: There were no differences in SOD and CAT activities between patients and controls. However, GSH Px activity was significantly lower in the iron-deficient children. Platelet aggregation responses to collagen and ADP were also significantly higher in iron deficient children than in controls. CONCLUSIONS: Decreased antioxidant defense in IDA may cause increased oxidant stress, which, in turn, may result in a tendency towards platelet aggregation. PMID- 11208004 TI - Endomysium antibodies in the diagnosis of celiac disease in short-statured children with no gastrointestinal symptoms. AB - BACKGROUND: Endomysium antibodies (EmAb) are strongly associated with untreated celiac disease and are suggested to be diagnostic. The aim of the present study was to assess the value of anti-EmAb for celiac disease screening in children with short stature. METHODS: In 84 children with height less than the third percentile for age, preliminary work-ups were made to find a cause for their short stature and then their serum was assayed for anti-EmAb by indirect immunofluorescence tests using monkey esophagus. RESULTS: Seven children were strongly positive for EmAb and all had positive histologic findings for celiac disease. CONCLUSIONS: Our results show that there is an association with occult celiac disease and idiopathic short stature and that the serum anti-EmAb test is useful in identifying such cases. PMID- 11208006 TI - A newborn infant with lipoprotein glomerulopathy associated with congenital nephrotic syndrome. PMID- 11208007 TI - Vertebral osteomyelitis and paravertebral abscess due to Salmonella oranienburg in a child. PMID- 11208008 TI - Tumor cell lysis syndrome resulting from transient abnormal myelopoiesis in a neonate with Down's syndrome. PMID- 11208009 TI - Precocious puberty in a girl with congenital hypothyroidism receiving continuous L-thyroxine-replacement therapy. PMID- 11208010 TI - A 4-month-old infant showing anemia, granulocytopenia and thrombocytopenia probably due to autoreactive IgG. PMID- 11208011 TI - Transient remission of intractable systemic-type of juvenile rheumatoid arthritis after chickenpox in a 2-year-old boy. PMID- 11208012 TI - An injection needle as a foreign body in the trachea resulting from asthma inhalation therapy. PMID- 11208013 TI - Oromandibular-limb hypogenesis with pulmonary hypoplasia. PMID- 11208014 TI - Highly suspected case of FAPA (periodic fever, aphthous stomatitis, pharyngitis and adenitis) syndrome. PMID- 11208015 TI - Free carnitine concentrations in cord blood in preterm and full-term infants with intrauterine growth retardation. PMID- 11208016 TI - Elevated serum levels of soluble interleukin-2 receptor in juvenile dermatomyositis. PMID- 11208017 TI - A novel cold-inducible zinc finger protein from soybean, SCOF-1, enhances cold tolerance in transgenic plants. AB - Cold stress on plants induces changes in the transcription of cold response genes. A cDNA clone encoding C2H2-type zinc finger protein, SCOF-1, was isolated from soybean. The transcription of SCOF-1 is specifically induced by low temperature and abscisic acid (ABA) but not by dehydration or high salinity. Constitutive overexpression of SCOF-1 induced cold-regulated (COR) gene expression and enhanced cold tolerance of non-acclimated transgenic Arabidopsis and tobacco plants. SCOF-1 localized to the nucleus but did not bind directly to either C-repeat/dehydration (CRT/DRE) or ABA responsive element (ABRE), cis acting DNA regulatory elements present in COR gene promoters. However, SCOF-1 greatly enhanced the DNA binding activity of SGBF-1, a soybean G-box binding bZIP transcription factor, to ABRE in vitro. SCOF-1 also interacted with SGBF-1 in a yeast two-hybrid system. The SGBF-1 transactivated the beta-glucuronidase reporter gene driven by the ABRE element in Arabidopsis leaf protoplasts. Furthermore, the SCOF-1 enhanced ABRE-dependent gene expression mediated by SGBF 1. These results suggest that SCOF-1 may function as a positive regulator of COR gene expression mediated by ABRE via protein-protein interaction, which in turn enhances cold tolerance of plants. PMID- 11208018 TI - Plastid-expressed 5-enolpyruvylshikimate-3-phosphate synthase genes provide high level glyphosate tolerance in tobacco. AB - Plastid transformation (transplastomic) technology has several potential advantages for biotechnological applications including the use of unmodified prokaryotic genes for engineering, potential high-level gene expression and gene containment due to maternal inheritance in most crop plants. However, the efficacy of a plastid-encoded trait may change depending on plastid number and tissue type. We report a feasibility study in tobacco plastids to achieve high level herbicide resistance in both vegetative tissues and reproductive organs. We chose to test glyphosate resistance via over-expression in plastids of tolerant forms of 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). Immunological, enzymatic and whole-plant assays were used to prove the efficacy of three different prokaryotic (Achromobacter, Agrobacterium and Bacillus) EPSPS genes. Using the Agrobacterium strain CP4 EPSPS as a model we identified translational control sequences that direct a 10,000-fold range of protein accumulation (to >10% total soluble protein in leaves). Plastid-expressed EPSPS could provide very high levels of glyphosate resistance, although levels of resistance in vegetative and reproductive tissues differed depending on EPSPS accumulation levels, and correlated to the plastid abundance in these tissues. Paradoxically, higher levels of plastid-expressed EPSPS protein accumulation were apparently required for efficacy than from a similar nuclear-encoded gene. Nevertheless, the demonstration of high-level glyphosate tolerance in vegetative and reproductive organs using transplastomic technology provides a necessary step for transfer of this technology to other crop species. PMID- 11208019 TI - Resistance to the plant PR-5 protein osmotin in the model fungus Saccharomyces cerevisiae is mediated by the regulatory effects of SSD1 on cell wall composition. AB - The capacity of plants to counter the challenge of pathogenic fungal attack depends in part on the ability of plant defense proteins to overcome fungal resistance by being able to recognize and eradicate the invading fungi. Fungal genes that control resistance to plant defense proteins are therefore important determinants that define the range of fungi from which an induced defense protein can protect the plant. Resistance of the model fungus Saccharomyces cerevisiae to osmotin, a plant defense PR-5 protein, is strongly dependent on the natural polymorphism of the SSD1 gene. Expression of the SSD1-v allele afforded resistance to the antifungal protein. Conversely, yeast strains carrying the SSD1 d allele or a null ssd1Delta mutation displayed high sensitivity to osmotin. The SSD1-v protein mediates osmotin resistance in a cell wall-dependent manner. Deletion of SSD1-v or SSD1-d impeded sorting of the PIR proteins (osmotin resistance factors) to the cell wall without affecting mRNA levels, indicating that SSD1 functions in post-transcriptional regulation of gene expression. The sensitivity of ssd1Delta cells to osmotin was only partially suppressed by over accumulation of PIR proteins in the cell wall, suggesting an additional function for SSD1 in cell wall-mediated resistance. Accordingly, cells carrying a null ssd1 mutation also displayed aberrant cell-wall morphology and lower levels of alkali-insoluble cell-wall glucans. Therefore SSD1 is an important regulator of fungal cell-wall biogenesis and composition, including the deposition of PIR proteins which block the action of plant antifungal PR-5 proteins. PMID- 11208020 TI - The spatial expression patterns of a phosphate transporter (MtPT1) from Medicago truncatula indicate a role in phosphate transport at the root/soil interface. AB - The movement of phosphate from the soil into plant root cells is the first of many crucial transport events required to supply phosphorous (P) to cells throughout the plant. In addition to the ability to acquire phosphate from the soil, the majority of the vascular plants are able to form arbuscular mycorrhizal associations in which phosphate may be delivered to the cortex via a fungus. Previously, we cloned two phosphate transporter genes, MtPT1 and MtPT2 from Medicago truncatula roots. Complementation of a yeast phosphate transport mutant revealed that MtPT1 is a functional phosphate transporter and Northern analyses revealed that MtPT1 is expressed exclusively in roots (Liu et al., 1998, Mol. Plant-Microbe Interact. 11, 14--22). Utilising an antibody specific for MtPT1, we have analysed the accumulation and spatial expression patterns of the MtPT1 transporter. MtPT1 transcript and protein levels show close correlation and increase dramatically in the roots in response to phosphate starvation. MtPT1 protein levels decrease in roots during development of a symbiosis with arbuscular mycorrhizal (AM) fungi, indicating that this transporter is not involved in symbiotic phosphate transport. Membrane fractionation and analysis of a MtPT1/GFP fusion protein revealed that MtPT1 is located in the plasma membrane, while in situ hybridisation and immunolocalisation demonstrate the presence of MtPT1 transcripts and protein in the epidermal cells and root hairs of M. truncatula roots. MtPT1 shows expression patterns consistent with a role specifically in the acquisition of phosphate from the soil and is distinct from the other phosphate transporter of this class described to date. PMID- 11208021 TI - The ABI1 and ABI2 protein phosphatases 2C act in a negative feedback regulatory loop of the abscisic acid signalling pathway. AB - The Arabidopsis ABI1 and ABI2 genes encode two protein serine/threonine phosphatases 2C (PP2C). These genes have been originally identified by the dominant mutations abi1--1 and abi2--1, which reduce the plant's responsiveness to the hormone abscisic acid (ABA). However, recessive mutants of ABI1 were recently shown to be supersensitive to ABA, which demonstrated that the ABI1 phosphatase is a negative regulator of ABA signalling. We report here the isolation and characterisation of the first reduction-of-function allele of ABI2, abi2--1R1. The in vitro phosphatase activity of the abi2--1R1 protein is approximately 100-fold lower than that of the wild-type ABI2 protein. Abi2--1R1 plants displayed a wild-type ABA sensitivity. However, doubly mutant plants combining the abi2--1R1 allele and a loss-of-function allele at the ABI1 locus were more responsive to ABA than each of the parental single mutants. These data indicate that the wild-type ABI2 phosphatase is a negative regulator of ABA signalling, and that the ABI1 and ABI2 phosphatases have overlapping roles in controlling ABA action. Measurements of PP2C activity in plant extracts showed that the phosphatase activity of ABI1 and ABI2 increases in response to ABA. These results suggest that ABI1 and ABI2 act in a negative feedback regulatory loop of the ABA signalling pathway. PMID- 11208022 TI - Genes determining pathogenicity to pea are clustered on a supernumerary chromosome in the fungal plant pathogen Nectria haematococca. AB - Three genes that contribute to the ability of the fungus Nectria haematococca to cause disease on pea plants have been identified. These pea pathogenicity (PEP) genes are within 25 kb of each other and are located on a supernumerary chromosome. Altogether, the PEP gene cluster contains six transcriptional units that are expressed during infection of pea tissue. The biochemical function of only one of the genes is known with certainty. This gene, PDA1, encodes a specific cytochrome P450 that confers resistance to pisatin, an antibiotic produced by pea plants. The three new PEP genes, in addition to PDA1, can independently increase the ability of the fungus to cause lesions on pea when added to an isolate lacking the supernumerary chromosome. Based on predicted amino acid sequences, functions for two of these three genes are hypothesized. The deduced amino acid sequence of another transcribed portion of the PEP cluster, as well as four other open reading frames in the cluster, have a high degree of similarity to known fungal transposases. Several of the features of the PEP cluster -- a cluster of pathogenicity genes, the presence of transposable elements, and differences in codon usage and GC content from other portions of the genome -- are shared by pathogenicity islands in pathogenic bacteria of plants and animals. PMID- 11208023 TI - Ethylene-dependent salicylic acid regulates an expanded cell death response to a plant pathogen. AB - The molecular events associated with susceptible plant responses to disease causing organisms are not well understood. We have previously shown that ethylene insensitive tomato plants infected with Xanthomonas campestris pv. vesicatoria have greatly reduced disease symptoms relative to wild-type cultivars. Here we show that salicylic acid (SA) is also an important component of the susceptible disease response. SA accumulates in infected wild-type tissues and is correlated with necrosis but does not accumulate in ethylene-insensitive plants. Exogenous feeding of SA to ethylene-deficient plants restores necrosis, indicating that reduced disease symptoms are associated with failure to accumulate SA. These results indicate a mechanism for co-ordination of phytohormone signals that together constitute a susceptible response to pathogens. PMID- 11208024 TI - Alteration of a single amino acid changes the substrate specificity of dihydroflavonol 4-reductase. AB - Many plant species exhibit a reduced range of flower colors due to the lack of an essential gene or to the substrate specificity of a biosynthetic enzyme. Petunia does not produce orange flowers because dihydroflavonol 4-reductase (DFR) from this species, an enzyme involved in anthocyanin biosynthesis, inefficiently reduces dihydrokaempferol, the precursor to orange pelargonidin-type anthocyanins. The substrate specificity of DFR, however, has not been investigated at the molecular level. By analyzing chimeric DFRs of Petunia and Gerbera, we identified a region that determines the substrate specificity of DFR. Furthermore, by changing a single amino acid in this presumed substrate-binding region, we developed a DFR enzyme that preferentially reduces dihydrokaempferol. Our results imply that the substrate specificity of DFR can be altered by minor changes in DFR. PMID- 11208025 TI - The MLA6 coiled-coil, NBS-LRR protein confers AvrMla6-dependent resistance specificity to Blumeria graminis f. sp. hordei in barley and wheat. AB - The barley Mla locus confers multiple resistance specificities to the obligate fungal biotroph, Blumeria (= Erysiphe) graminis f. sp. hordei. Interspersed within the 240 kb Mla complex are three families of resistance gene homologs (RGHs). Probes from the Mla-RGH1 family were used to identify three classes of cDNAs. The first class is predicted to encode a full-length CC-NBS-LRR protein and the other two classes contain alternatively spliced, truncated variants. Utilizing a cosmid that contains a gene corresponding to the full-length candidate cDNA, two single-cell expression assays were used to demonstrate complementation of AvrMla6-dependent, resistance specificity to B. graminis in barley and wheat. The first of these assays was also used to substantiate previous genetic data that the Mla6 allele requires the signaling pathway component, Rar1, for function. Computational analysis of MLA6 and the Rar1 independent, MLA1 protein reveals 91.2% identity and shows that the LRR domain is subject to diversifying selection. Our findings demonstrate that highly related CC-NBS-LRR proteins encoded by alleles of the Mla locus can dictate similar powdery mildew resistance phenotypes yet still require distinct downstream signaling components. PMID- 11208026 TI - Cytometric analysis of an epitope-tagged transit peptide bound to the chloroplast translocation apparatus. AB - Chloroplast transit peptides are necessary and sufficient for the targeting and translocation of precursor proteins across the chloroplast envelope. However, the mechanism by which transit peptides engage the translocation apparatus has not been investigated. To analyse this interaction, we have developed a novel epitope tagged transit peptide derived from the precursor of the small subunit of pea Rubisco. The recombinant transit peptide, His-S-SStp, contains a removable dual epitope tag, His-S, at its N-terminus that permits both rapid purification via immobilized metal affinity chromatography and detection by blotting, flow cytometry and laser-scanning confocal microscopy. Unlike other chimeric precursors, which place the passenger protein C-terminal to the transit peptide, His-S-SStp bound to the translocation apparatus yet did not translocate across the chloroplast envelope. This early translocation intermediate allowed non radioactive detection using fluorescent and chemiluminescent reporters. The physiological relevance of this interaction was confirmed by protein import competitions, sensitivity to pre- and post-import thermolysin treatment, photochemical cross-linking and organelle fractionation. The interaction was specific for the transit peptide since His-S alone did not engage the chloroplast translocation apparatus. Quantitation of the bound transit peptide was determined by flow cytometry, showing saturation of binding yet only slight ATP-dependence. The addition of GTP showed inhibition of the binding of His-S-SStp to the chloroplasts indicating an involvement of GTP in the formation of this early translocation intermediate. In addition, direct visualization of His-S-SStp and Toc75 by confocal microscopy revealed a patch-like labeling, suggesting a co ordinate localization to discrete regions on the chloroplast envelope. These findings represent the first direct visualization of a transit peptide interacting with the chloroplast translocation apparatus. Furthermore, identification of a chloroplast-binding intermediate may provide a novel tool to dissect interactions between a transit peptide and the chloroplast translocation apparatus. PMID- 11208027 TI - Increasing the proportion of diabetics with AV fistulas. AB - Worldwide, older diabetic patients represent the most rapidly growing group of patients treated for end-stage renal disease (ESRD). Preexisting arterial as well as venous problems have led to a pessimistic view on the creation of vascular access in this population. During 1993-98 I created all primary arteriovenous (AV) accesses for a total of 181 patients with diabetes mellitus (DM) ESRD and 567 patients with ESRD due to all other causes (non-DM). The following approach led to good outcomes for both groups whether assessed by time to first intervention or time to failure: careful preoperative investigations for selection of adequate location for initial AV fistula through ultrasonographic techniques; timely surgical AV fistula creation; preference of large-diameter, "healthy" arteries and veins, frequently requiring use of the elbow region; absolute priority for use of native vessels (i.e., avoidance of initial polytetrafluoroethylene [PTFE]); meticulous surgical technique and creativity; and continuous surveillance by the nephrologist and staff allowing elective revisions and avoidance of thrombosis. With this approach AV fistulas rather than PTFE grafts can be created in most diabetic and nondiabetic patients. PMID- 11208028 TI - Reconsidering the importance of long-term low-level aluminum exposure in renal failure patients. AB - Aluminum toxicity is widely considered a problem of the past. However, low-level aluminum exposure and low but abnormal body burdens of aluminum are common. Aluminon, the routinely used histochemical stain for aluminum in bone, has a low sensitivity. The role of aluminum in renal osteodystrophy needs to be reassessed using more sensitive techniques. Low-level aluminum exposure also may resu in subtle neurological dysfunction, another area that needs further investigation. PMID- 11208030 TI - Is Kt/V Urea a Satisfactory Measure for Dosing the Newer Dialysis Regimens? PMID- 11208029 TI - Is Kt/V urea a satisfactory measure for dosing the newer dialysis regimens? PMID- 11208031 TI - Is Kt/V Urea a Satisfactory Measure for Dosing the Newer Dialysis Regimens? PMID- 11208032 TI - Is Kt/V Urea a Satisfactory Measure for Dosing the Newer Dialysis Regimens? PMID- 11208033 TI - Is Kt/V Urea a Satisfactory Measure for Dosing the Newer Dialysis Regimens? PMID- 11208034 TI - Ethical issues in dialysis. Managing noncompliant dialysis patients. PMID- 11208035 TI - Must we treat noncompliant ESRD patients? AB - Coping with the stress induced by ESRD patient noncompliance is a time consuming, nonproductive, demoralizing undertaking that is unavoidable. An orderly, non confrontational approach encompassing measures to protect mentally incompetent and unaware patients as well as those too sick to comprehend and consent to therapy (dialysis) is provided. Individual practitioners should utilize all available resources including patient relatives and friends, collaborating psychiatrists, and institutional risk-management officers to assist in devising the best resolution to what may escalate into an onslaught against the renal care team. No single solution is applicable to the myriad variables that may impinge on a specific patient's seemingly apathetic or hateful behavior underlying noncompliance. PMID- 11208036 TI - There is a duty to treat noncompliant patients. PMID- 11208037 TI - Quantitative characterization of hemodialyzer solute and water transport. AB - Clinicians are frequently faced with the task of selecting a hemodialyzer for a dialysis-dependent patient. Several quantitative dialyzer parameters, such as clearance, sieving coefficients, and ultrafiltration coefficient, are routinely used in this selection process. However, the quantitative basis and exact meaning of these indices are often unclear or misinterpreted. The purpose of this article is to provide a detailed description of several of these parameters with the hope that this information will enable clinicians to make dialyzer selection from a more quantitative perspective. PMID- 11208038 TI - Noninfectious causes of cloudy peritoneal dialysate. AB - The appearance of cloudy dialysate fluid in combination with the clinical manifestations of peritonitis usually heralds infectious peritonitis. Diagnosis is readily established in most cases by routine culture of the turbid dialysate. However, an occasional patient presents with culture-negative, cloudy dialysate. After ruling out atypical infectious etiologies, a diverse set of aseptic causes remains in the differential diagnosis. Herein we review these causes and suggest an organizational scheme, based on identifying the cellular or noncellular constituent producing the dialysate turbidity, to facilitate appropriate diagnostic and therapeutic interventions. PMID- 11208039 TI - Individualizing the dialysate in the hemodialysis patient. AB - In most outpatient centers the dialysate is prepared centrally such that the composition of the dialysate is the same for all patients. When delivered in this manner most patients tolerate the procedure well. However, there are patients who tolerate the procedure poorly, which has prompted a great deal of research focused on individualizing the composition of the dialysate in order to improve patient tolerability. Prescribing a patient-specific dialysate will become increasingly important as the age of and number of comorbid conditions increase in the dialysis population. Patients with end-stage renal disease (ESRD) depend on dialysis to maintain fluid and electrolyte balance. Hemodialysis allows for solutes to diffuse between blood and dialysate such that, over the course of the procedure, plasma composition is restored toward normal values. The makeup of the dialysate is of paramount importance in accomplishing this goal. In most out patient settings patients receive hemodialysis using dialysate prepared in bulk and delivered via a central delivery system so that the composition of the dialysate is the same for all patients. While most patients tolerate the procedure when administered in this fashion, many patients suffer from hemodynamic instability or symptoms of dialysis disequilibrium. One strategy to improve the clinical tolerance to dialysis is to adjust the dialysate composition according to the individual characteristics of the patient. This article reviews recent developments on how the dialysate can be manipulated in order to improve patient tolerance. Individualizing the dialysate composition is likely to gain increasing importance given the advancing age and increasing number of comorbid conditions found in ESRD patients. PMID- 11208040 TI - Dialysate leaks in peritoneal dialysis. AB - Dialysate leakage represents a major noninfectious complication of peritoneal dialysis (PD). An exit-site leak refers to the appearance of any moisture around the PD catheter identified as dialysate; however, the spectrum of dialysate leaks also includes any dialysate loss from the peritoneal cavity other than via the lumen of the catheter. The incidence of dialysate leakage is somewhat more than 5% in continuous ambulatory peritoneal dialysis (CAPD) patients, but this percentage probably underestimates the number of early leaks. The incidence of hydrothorax or pleural leak as a complication of PD remains unclear. Factors identified as potentially related to dialysate leakage are those related to the technique of PD catheter insertion, the way PD is initiated, and weakness of the abdominal wall. The pediatric literature tends to favor Tenckhoff catheters over other catheters as being superior with respect to dialysate leakage, but no consensus on catheter choice exists for adults in this regard. An association has been found between early leaks (< or =30 days) and immediate CAPD initiation and perhaps median catheter insertion. Risk factors contributing to abdominal weakness appear to predispose mostly to late leaks; one or more of them can generally be identified in the majority of patients. Early leakage most often manifests as a pericatheter leak. Late leaks may present more subtly with subcutaneous swelling and edema, weight gain, peripheral or genital edema, and apparent ultrafiltration failure. Dyspnea is the first clinical clue to the diagnosis of a pleural leak. Late leaks tend to develop during the first year of CAPD. The most widely used approach to determine the exact site of the leakage is with computed tomography after infusion of 2 L of dialysis fluid containing radiocontrast material. Treatments for dialysate leaks include surgical repair, temporary transfer to hemodialysis, lower dialysate volumes, and PD with a cycler. Recent recommendation propose a standard approach to the treatment of early and late dialysate leaks: 1-2 weeks of rest from CAPD, and surgery if recurrence. Surgical repair has been strongly suggested for leakage causing genital swelling. Delaying CAPD for 14 days after catheter insertion may prevent early leakage. Initiating CAPD with low dialysate volume has also been recommended as a good practice measure. Although peritonitis and exit-site infections are the most frequent causes of technical failure in peritoneal dialysis (PD), dialysate leaks represent one of the major noninfectious complications of PD. In some instances, dialysate leakage may lead to discontinuation of the technique (1). Despite its importance, the incidence, risk factors, management, and outcome of dialysate leakage are poorly characterized in the literature. We will review the limited available information on this topic in the next few sections. PMID- 11208041 TI - Regulation of bone remodeling: impact of novel therapies. AB - The kidneys serve as both an endocrine organ and as a target of endocrine action, with the aim of controlling mineral and water balance. Hormones and other key metabolites regulate mineral homeostasis by altering gene function directly or by initiating a sequence of events, leading ultimately to a change in enzyme function. Two of these hormones, parathyroid hormone (PTH) and calcitriol (the active form of vitamin D), interact in multiple tissues in the body to regulate the flux of calcium and phosphorus between extra- and intracellular compartments. Changes in the concentration of PTH and vitamin D, or the interaction of these with other factors, lead to the aberrant regulation of calcium and phosphorus. Among other effects, this aberrant regulation leads to pathologic changes in bone metabolism. The pathology of renal bone disease varies along a spectrum from disorders of low turnover to those of high turnover. This spectrum reflects the results of therapeutic intervention, hormone balances, and other causes. Effective management of renal bone disease therefore requires thorough evaluation of relevant risk factors, measurement of biochemical markers of bone remodeling, and determination of the physical status of bone tissue either by bone mineral density or bone biopsy. Subsequent therapeutic intervention with newer vitamin D compounds, novel phosphate binders, calcimimetics, and the use of alternative dialysis modalities offer hope in normalizing bone remodeling and mineral balance. The human skeleton functions in two capacities: the storage of minerals and structural support of the body. It is the only tissue that behaves as both a major source and a sink of calcium (Ca) and phosphorus (P). Healthy bone is a composite of a collagenous matrix embedded with crystals of hydroxyapatite. On the surface of bone and within the calcified matrix are specialized cells that build and maintain the tissue, and facilitate the movement of Ca and P into and out of serum. Bone undergoes remodeling in response to either damage from mechanical strain or as part of the normal cycle of bone renewal. The process involves distinct steps of cellular activation, bone resorption, and subsequent bone formation. It is a relatively slow process that takes several months, and at any one time occurs at many different sites along the bone surface. Systemic factors, such as PTH and vitamin D, regulate the resorption and formation of bone, and thus the systemic movement of Ca and P. However, during conditions of stress and disease, other factors may also play a role. In patients with chronic renal disease, the balance of Ca and P is profoundly disturbed. This disruption and the compensatory changes that occur in response alter the normal processes of bone metabolism. PMID- 11208042 TI - Pericarditis associated with renal failure: evolution and management. PMID- 11208043 TI - Wide complex tachycardia in a dialysis patient. PMID- 11208044 TI - Sip, sip, sippy. PMID- 11208045 TI - Vitamin E for dialysis patients. PMID- 11208046 TI - Use of aspirin in hemodialysis patients. PMID- 11208047 TI - Beta-blocker use in peritoneal dialysis patients. PMID- 11208048 TI - The "pinch off" syndrome. PMID- 11208049 TI - The seventh day: a day of unrest. PMID- 11208050 TI - The hem of the garment. PMID- 11208053 TI - Motors, clutches and brakes for membrane traffic: a commemorative review in honor of Thomas Kreis. AB - Membranous organelles interact with a wide variety of cytoskeletal proteins that allow them to be organized into dynamic, yet stable, structures with distinct subcellular addresses. This review provides an up-to-date summary of the motor enzymes and membrane-microtubule crosslinking proteins that have been implicated in this process, and discusses the potential impact membrane anchoring may have on cellular architecture. PMID- 11208054 TI - Unconventional myosins: anchors in the membrane traffic relay. AB - The family of unconventional myosins is ever growing and the functions attributed to them seem to expand in parallel. These actin-based motor proteins have been implicated in processes as seemingly diverse as endocytosis and exocytosis, the transport of organelles, in spermatogenesis and in neurosensory functions such as hearing and sight. A common myosin function may underlie them all--the regulation of intracellular membrane traffic. PMID- 11208055 TI - The polymerization motor. AB - Polymerization and depolymerization of actin filaments and microtubules are thought to generate force for movement in various kinds of cell motility, ranging from lamellipodial protrusion to chromosome segregation. This article reviews the thermodynamic and physical theories of how a nonequilibrium polymerization reaction can be used to transduce chemical energy into mechanical energy, and summarizes the evidence suggesting that actin polymerization produces motile force in several biological systems. PMID- 11208056 TI - Stirring up development with the heterotrimeric kinesin KIF3. AB - KIF3 is a heterotrimeric member of the kinesin superfamily of microtubule associated motors. This functionally diverse family of motor is involved in anterograde transport of membrane bound organelles in neurons and melanosomes, mediates transport between the endoplasmic reticulum and the Golgi, and transports protein complexes within cilia and flagella required for their morphogenesis. Interestingly, a mutation of KIF3, which impairs ciliogenesis in nodal cells, prevents the unidirectional leftward flow (nodal flow) of putative morphogens during embryogenesis, thereby altering the development of left-right asymmetry in mammals. PMID- 11208057 TI - Membrane traffic in anaglyph stereo. PMID- 11208058 TI - Mitotic phosphorylation of the dynein light intermediate chain is mediated by cdc2 kinase. AB - Cytoplasmic dynein, a large minus-end-directed microtubule motor, performs multiple functions during the cell cycle. In interphase, dynein moves membrane organelles, while in mitosis it moves chromosomes and helps to form the mitotic spindle. The cell-cycle regulation of dynein activity may be controlled, at least in part, by the phosphorylation of its light intermediate chains (DLIC), since a 10-fold increase in light intermediate chain phosphorylation correlates with a decrease in dynein-based membrane transport of similar magnitude in mitosis. In this study, we sought to identify the kinase responsible for this potentially important phosphorylation event. We show that bacterially-expressed chicken light intermediate chain (chDLIC) will undergo mitosis-specific phosphorylation when added to Xenopus egg extracts. Mutation of a conserved cdc2 kinase consensus site (Ser197) abolishes this phosphorylation event, and mass spectroscopy analysis confirms that the wild-type DLIC is stoichiometrically phosphorylated at this site when incubated with metaphase but not interphase extracts. We also show that purified cdc2 kinase phosphorylates purified DLICs at Ser197 in vitro and that Ser197 phosphorylation is dramatically reduced in metaphase extracts depleted of cdc2 kinase. These results indicate that cdc2 kinase directly phosphorylates dynein and thus may be an important regulator of dynein activity in the cell cycle. PMID- 11208059 TI - The yeast endosomal t-SNARE, Pep12p, functions in the absence of its transmembrane domain. AB - Delivery of proteins to the vacuole of the yeast Saccharomyces cerevisiae requires the function of two distinct SNARE complexes. Pep12p and Vam3p are both t-SNAREs of the syntaxin family that are components of these SNARE complexes. We have used a genetic approach to address the role of Pep12p in vacuolar protein transport. Our screen for temperature-sensitive pep12 mutants yielded six alleles that were rapidly inactivated upon exposure to the non-permissive temperature. Surprisingly, the proteins encoded by these alleles were all truncated immediately prior to the transmembrane domain. Here we demonstrate that Pep12p requires its transmembrane domain for proper localization, but not for its role in vesicle fusion. In addition, we show that although Pep12p can replace Vam3p in the vacuolar SNARE complex, its transmembrane domain is required to function at this step. Therefore, the transmembrane domain of Pep12p performs different roles in the prevacuolar and vacuolar SNARE complexes. PMID- 11208060 TI - Morphogenesis and dynamics of the yeast Golgi apparatus. AB - A kinetic and morphometric study was conducted with the electron microscope to clarify the biogenesis and structural diversity of the Golgi apparatus in the yeast Saccharomyces cerevisiae. Secretion was synchronized by inhibiting protein synthesis and/or by subjecting thermosensitive secretory mutants to double temperature shifts. Five membrane-bounded structures disappeared or reappeared in an orderly manner at approximately the rate of secretory protein flow. 1) The first detectable post-ER intermediates were very short-lived clusters of small vesicles that appeared next to the endoplasmic reticulum (ER). 2) Their constituent small vesicles were rapidly bridged by membrane tubules in a SEC18 dependent manner, giving short-lived tubular clusters of small vesicles, analogous to mammalian vesicular-tubular clusters. 3) Fine and 4) large nodular networks (coated with the Golgi protein Sec7), and 5) secretory granules. Upon relieving a secretory block, each structure successively reappeared, seemingly by transformation of the previous one. When no secretory cargo was to be transported, these structures were not renewed. They disappeared more than five times faster than some Golgi enzymes such as Och1p, implying that the latter are recycled and perhaps partially retained. Retention could arise from intra compartmental flow of cargo/carrier, hinted at by the varying calibers within a single nodular network. PMID- 11208061 TI - Complete reconstitution of clathrin basket formation with recombinant protein fragments: adaptor control of clathrin self-assembly. AB - Clathrin polymerization into a polyhedral basket, surrounding budding membrane vesicles, mediates protein sorting during endocytosis and organelle biogenesis. Adaptor proteins target clathrin assembly to specific membrane sites and sequester receptors into the clathrin coat. We have reconstituted complete clathrin basket formation from recombinantly expressed fragments of clathrin and adaptors. This reconstitution reveals a hierarchy of clathrin self-assembly interactions and demonstrates that adaptors control basket formation by alignment of the distal domains of the clathrin triskelion leg through their binding to the terminal domain. PMID- 11208063 TI - Membrane dynamics in endocytosis: structure--function relationship. AB - A number of years ago a small group of investigators was torn apart by a debate over the existence or fate of somewhat obscure endosomal vesicles not even represented in text books. During the last decade, however, interest has shifted with the fireworks of newly discovered molecules involved in the regulation of protein transport. We are now entering the post-genomic era, where individual components can be re-assembled into functional, multiprotein cellular machines. Borders between disciplines in Life Sciences are fading away as our molecular understanding approaches atomic resolution. It is these exciting developments that were captured by the latest edition of the ESF conference series on endocytosis. PMID- 11208062 TI - Microvillus inclusion disease: a genetic defect affecting apical membrane protein traffic in intestinal epithelium. AB - The striking similarities between microvillus inclusions (MIs) in enterocytes in microvillus inclusion disease (MID) and vacuolar apical compartment in tissue culture epithelial cells, led us to analyze endoscopic biopsies of duodenal mucosa of a patient after the samples were used for diagnostic procedures. Samples from another patient with an unrelated disease were used as controls. The MID enterocytes showed a decrease in the thickness of the apical F-actin layer, and normal microtubules. The immunofluorescence analysis of the distribution of five apical membrane markers (sucrase isomaltase, alkaline phosphatase, NHE-3 Na+/H+ exchanger, cGMP-dependent protein kinase, and cystic fibrosis trans membrane conductance regulator), showed low levels of these proteins in their standard localization at the apical membrane as compared with normal duodenal epithelium processed in parallel. Instead, four of these markers were found in a diffuse distribution in the apical cytoplasm, below the terminal web (as indicated by co-localization with F-actin and cytokeratin 19), and in MIs as well. The basolateral protein Na(+)-K+ATPase, in contrast, was normally localized. These results support the hypothesis that MID may represent the first genetic defect affecting apical membrane traffic, possibly in a late step of apical exocytosis. PMID- 11208064 TI - Proteomic tools for cell biology. AB - Acquisition of large bodies of genomic sequence is facilitating the use of global techniques to assay cellular function. DNA microarrays have enabled the measurement of global mRNA levels and are able to detect changes in gene expression between different cellular states. Since much of the regulation of physiological processes happens post-translationally, measuring only the mRNA levels gives an incomplete picture. Strategies to assay global expression, localization, or interaction of proteins fall into the emerging field of proteomics, with various combinations of techniques being utilized to separate and identify proteins. In this review, we will present a general overview of the currently available proteomic tools and then give examples of how these tools are being utilized to answer questions in cell biology. PMID- 11208065 TI - Watching proteins in the wild: fluorescence methods to study protein dynamics in living cells. AB - The advent of GFP imaging has led to a revolution in the study of live cell protein dynamics. Ease of access to fluorescently tagged proteins has led to their widespread application and demonstrated the power of studying protein dynamics in living cells. This has spurred development of next generation approaches enabling not only the visualization of protein movements, but correlation of a protein's dynamics with its changing structural state or ligand binding. Such methods make use of fluorescence resonance energy transfer and dyes that report changes in their environment, and take advantage of new chemistries for site-specific protein labeling. PMID- 11208066 TI - The use of yeast two-hybrid screens in studies of protein:protein interactions involved in trafficking. AB - The yeast two-hybrid system has provided a convenient means to both screen for proteins that interact with a protein of interest and to characterise the known interaction between two proteins. Several groups with an interest in the molecular mechanisms that underlie discrete steps along trafficking pathways have exploited the yeast two-hybrid system. Here, we provide a brief background to the technology, attempt to point out some of the pitfalls and benefits of the different systems that can be employed, and mention some of the areas (within the trafficking field) where yeast two-hybrid interaction assays have been particularly informative. PMID- 11208067 TI - Proteomic analysis of two functional states of the Golgi complex in mammary epithelial cells. AB - Organellar compartments involved in secretion are expanded during the transition from late pregnancy (basal secretory state) to lactation (maximal secretory state) to accommodate for the increased secretory function required for copious milk production in mammary epithelial cells. The Golgi complex is a major organelle of the secretory pathway and functions to sort, package, distribute, and post-translationally modify newly synthesized proteins and membrane lipids. These complex functions of the Golgi are reflected in the protein complement of the organelle. Therefore, using proteomics, the protein complements of Golgi fractions isolated at two functional states (basal and maximal) were compared to identify some of the molecular changes that occur during this transition. This global analysis has revealed that only a subset of the total proteins is upregulated from steady state during the transition. Identification of these proteins by tandem mass spectrometry has revealed several classes of proteins involved in the regulation of membrane fusion and secretion. This first installment of the functional proteomic analysis of the Golgi complex begins to define the molecular basis for the transition from basal to maximal secretion. PMID- 11208068 TI - Weibel-Palade body membrane proteins exhibit differential trafficking after exocytosis in endothelial cells. AB - Weibel-Palade bodies, the secretory granules of endothelial cells, possess two different membrane proteins. However, P-selectin is seen only in Weibel-Palade bodies in HUVECs, whereas CD63 is also seen in late endosomes/lysosomes. Since P selectin is targeted to lysosomes in heterologous expression studies, we have determined whether a lysosomal targeting signal also operates within HUVECs. We have also examined the trafficking of CD63 to its two different intracellular locations. By following antibodies bound at the plasma membrane during stimulation, we have discovered that while half of the P-selectin recycles to the WPBs, 50% is rapidly delivered to a lamp-1-positive compartment. Thus, the lysosomal targeting signal of this protein also operates in HUVECs. CD63 is found constitutively at the cell surface of HUVECs and most of it is delivered to the late endosomes/lysosomes after internalisation. However, stimulation causes both a rise in the CD63 plasma membrane level and in the amount that recycles to the WPBs. Our data strongly suggest that the CD63 that originates in the WPB preferentially recycles to the granule rather than being delivered to the late endosome/lysosome, and that there are, therefore, two separate pools of this protein within HUVECs. Our findings indicate that although P-selectin and CD63 are both targeted to the same compartments from the PM, the kinetics and the ratio of their targeting to Weibel-Palade bodies versus lysosomes are very different. PMID- 11208069 TI - Detergent insoluble microdomains are not involved in transcytosis of polymeric Ig receptor in FRT and MDCK cells. AB - In polarized epithelial cells, sorting of proteins and lipids to the apical or basolateral domain of the plasma membrane can occur via direct or indirect (transcytotic) pathways from the trans Golgi network (TGN). The 'rafts' hypothesis postulates that the key event for direct apical sorting of some transmembrane proteins and the majority of GPI-anchored proteins depends on their association with glycosphingolipid and cholesterol enriched microdomains (rafts). However, the mechanism of indirect sorting to the apical membrane is not clear. The polyimmunoglobulin receptor (pIgR) is one of the best studied proteins that follow the transcytotic pathway. It is normally delivered from the TGN to the basolateral surface of polarized Madin-Darby Canine Kidney (MDCK) cells from where it transports dIgA or dIgM to the apical surface. We have studied the intracellular trafficking of pIgR in Fischer rat thyroid cells (FRT), and have investigated the sorting machinery involved in transcytosis of this receptor in both FRT and MDCK cells. We found that, in contrast with MDCK cells, a significant amount (approximately 30%) of pIgR reaches the apical surface by a direct pathway. Furthermore, in both cell lines it does not associate with Triton X-100 insoluble microdomains, suggesting that at least in these cells 'rafts' are not involved in basolateral to apical transcytosis. PMID- 11208070 TI - Biomolecule function: no reliable prediction from cell culture. PMID- 11208072 TI - Analysis of the lysosomal storage disease Chediak-Higashi syndrome. AB - Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder of human, mouse (beige) and other mammalian species. The same genetic defect was found to result in the disease in all species identified, permitting a positional cloning approach using the mouse model beige to identify the responsible gene. The CHS gene was cloned and mutations identified in affected species. This review discusses the clinical features of CHS contrasting features seen in similar syndromes. The possible functions of the protein encoded by the CHS/beige gene are discussed, along with the alterations in cellular physiology seen in mutant cells. PMID- 11208071 TI - Membrane traffic in sphingolipid storage diseases. AB - In this review, we summarize our studies of membrane lipid transport in sphingolipid storage disease (SLSD) fibroblasts. We recently showed that several fluorescent SL analogs were internalized from the plasma membrane predominantly to the Golgi complex of normal cells, while in ten different SLSD cell types, these lipids accumulated in endosomes and lysosomes (The Lancet 1999;354: 901 905). Additional studies showed that cholesterol homeostasis is perturbed in multiple SLSDs secondary to SL accumulation and that mistargeting of SL analogs was regulated by cholesterol (Nature Cell Biol 1999;1: 386-388). Based on these findings, we hypothesize that endogenous sphingolipids, which accumulate in SLSD cells due to primary defects in lipid catabolism, result in an altered intracellular distribution of cholesterol, and that this alteration in membrane composition then results in defective sorting and transport of SLs. The importance of SL/cholesterol interactions and potential mechanisms underlying the regulation of lipid transport and targeting are also discussed. These studies suggest a new paradigm for regulation of membrane lipid traffic along the endocytic pathway and could have important implications for future studies of protein trafficking as well as lipid transport. This work may also lead to important future clinical developments (e.g. screening tests for SLSD, new methodology for screening drugs which abrogate lipid storage, and possible therapeutic approaches to SLSD). PMID- 11208073 TI - Hermansky-Pudlak syndrome and related disorders of organelle formation. AB - Hermansky-Pudlak syndrome (HPS) consists of a group of genetically heterogeneous disorders which share the clinical findings of oculocutaneous albinism, a platelet storage pool deficiency, and some degree of ceroid lipofuscinosis. Related diseases share some of these findings and may exhibit other symptoms and signs but the underlying defect in the entire group of disorders involves defective intracellular vesicle formation, transport or fusion. Two HPS-causing genes, HPS1 and ADTB3A, have been isolated but the function of only the latter has been determined. ADTB3A codes for the beta 3A subunit of adaptor complex-3, responsible for vesicle formation from the trans-Golgi network (TGN). The many HPS patients who do not have HPS1 or ADTB3A mutations have their disease because of mutations in other genes. Candidates for these HPS-causing genes include those responsible for mouse models of HPS or for the 'granule' group of eye color genes in Drosophila. Each gene responsible for a subset of HPS or a related disorder codes for a protein which almost certainly plays a pivotal role in vesicular trafficking, inextricably linking clinical and cell biological interests in this group of diseases. PMID- 11208074 TI - Traffic jam: a compendium of human diseases that affect intracellular transport processes. AB - As sequencing of the human genome nears completion, the genes that cause many human diseases are being identified and functionally described. This has revealed that many human diseases are due to defects of intracellular trafficking. This 'Toolbox' catalogs and briefly describes these diseases. PMID- 11208075 TI - Traffic pattern of cystic fibrosis transmembrane regulator through the early exocytic pathway. AB - The pathway of transport of the cystic fibrosis transmembrane regulator (CFTR) through the early exocytic pathway has not been examined. In contrast to most membrane proteins that are concentrated during export from the ER and therefore readily detectable at elevated levels in pre-Golgi intermediates and Golgi compartments, wild-type CFTR could not be detected in these compartments using deconvolution immunofluorescence microscopy. To determine the basis for this unusual feature, we analyzed CFTR localization using quantitative immunoelectron microscopy (IEM). We found that wild-type CFTR is present in pre-Golgi compartments and peripheral tubular elements associated with the cis and trans faces of the Golgi stack, albeit at a concentration 2-fold lower than that found in the endoplasmic reticulum (ER). delta F508 CFTR, a mutant form that is not efficiently delivered to the cell surface and the most common mutation in cystic fibrosis, could also be detected at a reduced concentration in pre-Golgi intermediates and peripheral cis Golgi elements, but not in post-Golgi compartments. Our results suggest that the low level of wild-type CFTR in the Golgi region reflects a limiting step in selective recruitment by the ER export machinery, an event that is largely deficient in delta F508. We raise the possibility that novel modes of selective anterograde and retrograde traffic between the ER and the Golgi may serve to regulate CFTR function in the early secretory compartments. PMID- 11208076 TI - Two independent regions of HIV-1 Nef are required for connection with the endocytic pathway through binding to the mu 1 chain of AP1 complex. AB - The Nef protein from the human immunodeficiency virus (HIV) induces down regulation of the CD4 and major histocompatibility complex class I molecules from the cell surface by interfering with the endocytic machinery. This work focuses on the interaction of HIV-1 Nef with the mu 1 chain of adaptor protein type 1 (AP1) complex and its contribution to the Nef-induced alterations of membrane trafficking. Two independent regions surrounding a disordered loop located in the C-terminal part of Nef are involved in mu 1 binding. Each region can separately interact with mu 1, and simultaneous point mutations within both regions are needed to abolish binding. We used CD8 chimeras in which the cytoplasmic tail was replaced by Nef mutants to show that these mu 1-binding sites contain determinants required to induce CD4 down-regulation and to target the chimera to the endocytic pathway by promoting AP1 complex recruitment. Ultrastructural analysis revealed that the CD8-Nef chimera provokes morphological alterations of the endosomal compartments and co-localizes with AP1 complexes. These data indicate that the recruitment by Nef of AP1 via binding to mu 1 participates in the connection of Nef with the endocytic pathway. PMID- 11208077 TI - Targeting of HIV-1 Nef to the centrosome: implications for antigen processing. AB - To gain a better understanding of the intracellular sites of antigen processing we have looked at the localization of human immunodeficiency virus (HIV)-1 Nef protein by confocal microscopic and biochemical means. We found that ubiquitin (Ub)-Nef fusion proteins were localized to the centrosome in transfected COS-7 cells, and that the colocalization was inhibited by the microtubule-disrupting agent, nocodazole. Interestingly, we found that Ub-Nef trafficking to the centrosome was not dependent upon the metabolic stability of Ub-Nef nor on the inhibition of proteasome activity. We also analyzed the MHC class I antigen processing of a reporter epitope linked to the Ub-Nef fusion proteins and found that Ub-Nef was processed in COS-7 cells. In addition, we show that this processing was inhibited by nocodazole. We suggest that the centrosome may serve as a site of antigen processing in vivo. PMID- 11208079 TI - Overexpression of a novel sorting nexin, SNX15, affects endosome morphology and protein trafficking. AB - Sorting nexin (SNX) 15 is a novel member of the SNX family of proteins. Although the functions of most SNXs have not yet been determined, several family members (e.g., SNX1, SNX2, SNX3, and SNX8) are orthologs of yeast proteins involved in protein trafficking. Overexpression of myc-tagged SNX15 in COS-7 cells altered the morphology of several endosomal compartments. In transient transfection experiments, myc-SNX15 was first seen in small punctate spots and small ring structures. Later, myc-SNX15 was found in larger rings. Finally, myc-SNX15 was observed in large, amorphous membrane-limited structures. These structures contained proteins from lysosomes, late endosomes, early endosomes, and the trans Golgi network. However, the morphology of the endoplasmic reticulum and Golgi was not affected by overexpression of myc-SNX15. In myc-SNX15-overexpressing cells, the endocytosis of transferrin was severely inhibited and endocytosis of tac trans-Golgi network (TGN) 38 and tac-furin was slowed. In addition, the recycling of internalized tac-TGN38 and tac-furin was also inhibited. Both the morphological and biochemical data indicate that SNX15 plays a crucial role in trafficking through the endocytic pathway. This is the first demonstration that a mammalian SNX protein is involved in protein trafficking. PMID- 11208080 TI - Advocacy for biomedical research: looking back, looking forward. PMID- 11208081 TI - Membrane traffic and cytokinesis. AB - Cytokinesis, the last step in cell division, is a process common to all eukaryotic life forms. The many mechanisms cells use to divide one parent cell into two progeny reflect the diversity of eukaryotic life. Despite the varied mechanisms cells use, increasing evidence demonstrates that many different cells use 'classical' membrane trafficking proteins for cytokinesis. This review highlights recent evidence for roles for membrane trafficking proteins in cytokinesis. PMID- 11208082 TI - Construction of centrosomes and spindle poles by molecular motor-driven assembly of protein particles. AB - Centrosomes and other microtubule organizing centers are the largest non membranous organelles in most cells. This morphologically diverse class of organelles shares a common ability to nucleate and organize microtubules in interphase and participates in the formation of mitotic spindles during cell division. This review summarizes recent evidence suggesting that assembly of centrosomes and mitotic spindle poles require transport of large protein particles along microtubules by the molecular motor cytoplasmic dynein. PMID- 11208083 TI - Raising the speed limits for 4D fluorescence microscopy. AB - Three-dimensional time-lapse (4D) fluorescence microscopy is becoming a routine experimental tool. This article summarizes current technologies, and describes a new method for speeding image acquisition during 4D confocal microscopy. PMID- 11208084 TI - Purification of the vertebrate nuclear pore complex by biochemical criteria. AB - The nuclear pore is a large and complex biological machine, mediating all signal directed transport between the nucleus and the cytoplasm. The vertebrate pore has a mass of approximately 120 million daltons or 30 times the size of a ribosome. The large size of the pore, coupled to its tight integration in the nuclear lamina, has hampered the isolation of pore complexes from vertebrate sources. We have now developed a strategy for the purification of nuclear pores from in vitro assembled annulate lamellae (AL), a cytoplasmic mimic of the nuclear envelope that lacks a lamina, nuclear matrix, and chromatin-associated proteins. We find that purified pore complexes from annulate lamellae contain every nuclear pore protein tested. In addition, immunoblotting reveals the presence of soluble transport receptors and factors known to play important roles in the transport of macromolecules through the pore. While transport factors such as Ran and NTF2 show only transient interaction with the pores, a number of soluble transport receptors, including importin beta, show a tight association with the purified pores. In summary, we report that we have purified the vertebrate pore by biochemical criteria; silver staining reveals approximately 40-50 distinct protein bands. PMID- 11208085 TI - Cholesterol is required for the formation of regulated and constitutive secretory vesicles from the trans-Golgi network. AB - We studied the role of cholesterol in regulated protein secretion in neuroendocrine cells by manipulating the cholesterol content of AtT-20 cells. Depletion of cellular cholesterol levels caused a reversible block of immature secretory granule biogenesis at the level of the trans-Golgi-network, whereas increased cholesterol levels promoted immature secretory granule formation. Cholesterol depletion also blocked the formation of constitutive secretory vesicles, but did not inhibit the transport between the endoplasmic reticulum and the Golgi complex. Our results indicate that the assembly of cholesterol-based lipid microdomains is required for the biogenesis of both regulated and constitutive secretory vesicles from the trans-Golgi-network in neuroendocrine cells. PMID- 11208086 TI - GMx33: a novel family of trans-Golgi proteins identified by proteomics. AB - The known functions of the Golgi complex include the sorting, packaging, post translational modification, and transport of secretory proteins, membrane proteins, and lipids. Other functions still remain elusive to cell biologists. With the goal of identifying novel Golgi proteins, a proteomics project was undertaken to map the major proteins of the organelle using two-dimensional gels, to identify the unknowns using tandem mass spectrometry, and to screen for Golgi residents using GFP-fusion constructs. Multiple unknowns were identified, and the initial characterization of one of these proteins is reported here. GMx33 alpha is a member of a conserved family of cytosolic Golgi-associated proteins with no known homology to any known functional domain or protein. Biochemical analyses show that GMx33 alpha differentially partitions into all phases of multiple detergent extractions, and two-dimensional immunoblots reveal that there are multiple differentially modified forms of GMx33 alpha associated with the Golgi, several of which are phosphorylated. Evidence suggests that these post translational modifications regulate its association with the Golgi. GMx33 alpha was not found on Golgi budded vesicles, and immuno-electron microscopy co localizes GMx33 alpha to the trans-face on the same three cisternae as TGN38 in normal rat kidney cells. This work represents the preliminary characterization of a novel family of trans-Golgi-associated proteins. PMID- 11208087 TI - Rab3A and Rab3D control the total granule number and the fraction of granules docked at the plasma membrane in PC12 cells. AB - Rab proteins are Ras-like GTPases that regulate traffic along the secretory or endocytic pathways. Within the Rab family, Rab3 proteins are expressed at high levels in neurons and endocrine cells where they regulate release of dense core granules and synaptic vesicles. Immunoelectron microscopy shows that Rab3A and Rab3D can coexist on the same granule before and after docking. Using electron microscopy of transfected PC12 cells, we report that expression of wild-type Rab3A (or Rab3D) increases the total number of granules and the percentage that is docked at the plasma membrane. Mutated Rab3A N135I (or Rab3D N135I) decreases the total granule number and the fraction of granules docked to the plasma membrane. These data show that at least one of the functions of Rab3A and Rab3D proteins is to control the number of granules docked at the plasma membrane. PMID- 11208089 TI - Redirection of host vesicle trafficking pathways by intracellular parasites. AB - Bacterial and protozoon intracellular parasites have evolved diverse mechanisms for evasion of host cellular defenses associated with adaptations for survival in distinct intracellular compartments. As the reagents identifying discrete steps in vesicle maturation and trafficking have become increasingly available, it has become clear that the vacuoles occupied by intracellular parasites are much more diverse than had been previously appreciated. Many parasites induce selective fusion competence with the vacuoles they occupy, without affecting vesicular trafficking elsewhere in the cell. A likely means of controlling vesicular interactions is modification of the parasitophorous vacuole membrane by the insertion of parasite-specific proteins. A rapidly expanding class of bacterial proteins that modify the vacuolar membrane are the chlamydial inclusion membrane proteins. Although the functions of most of these proteins remain to be defined, the majority are expressed early in the infectious process, suggesting that modification of the vacuole is critical to the outcome of the host-parasite interaction. PMID- 11208088 TI - Trafficking and folding defects in hereditary spherocytosis mutants of the human red cell anion exchanger. AB - Hereditary spherocytosis (HS) is a common inherited hemolytic anemia caused by mutations in erythrocyte proteins including the anion exchanger, AE1 (band 3). This study examined seven missense mutations (L707P, R760Q, R760W, R808C, H834P, T837M, and R870W) located in the membrane domain of the human AE1 that are associated with this disease. The HS mutants, constructed in full-length AE1 cDNA, could be transiently expressed to similar levels in HEK 293 cells. Immunofluorescence, cell surface biotinylation, and pulse chase labeling showed that the HS mutants all exhibited defective cellular trafficking from the endoplasmic reticulum to the plasma membrane. Impaired binding to an inhibitor affinity matrix indicated that the mutant proteins had non-native structures and may be misfolded. Further characterization of the HS R760Q mutant showed no change in its oligomeric structure or turnover (half-life = 15 h) compared to wild-type AE1, suggesting the mutant was not aggregated or targeted for rapid degradation via the proteasome. Intracellular retention of HS mutant AE1 would lead to destruction of the protein during erythroid development and would account for the lack of HS mutant AE1 in the plasma membrane of the mature red cell. PMID- 11208090 TI - Cell invasion by un-palatable parasites. AB - While some intracellular pathogens invade and replicate exclusively in phagocytic host cells, others have evolved mechanisms to stimulate their uptake by cells not equipped with a well-developed phagocytic machinery. A common mechanism utilized by bacteria involves the induction of macropinocytosis, or of other F-actin driven processes which result in engulfment of the pathogen through formation of a plasma membrane-derived vacuole. Interestingly, this type of "induced phagocytosis" mechanism does not appear to be utilized by protozoan parasites, which are significantly larger than bacteria in size (about 5-10 microns in average length). Intracellular protozoa either restrict themselves to infecting "professional" phagocytes (one example is the trypanosomatid Leishmania), or utilize highly unusual mechanisms for gaining access to the intracellular environment. Here we discuss what has been revealed in recent years about the remarkable cell invasion strategies of two highly successful intracellular parasites: Toxoplasma gondii and Trypanosoma cruzi. Toxoplasma utilizes a distinct form of actin/myosin-dependent gliding motility to propel itself into mammalian cells, while T. cruzi invades by subverting a Ca(2+)-regulated lysosomal exocytic pathway. PMID- 11208091 TI - Poisons, ruffles and rockets: bacterial pathogens and the host cell cytoskeleton. AB - The cytoskeleton of eukaryotic cells is affected by a number of bacterial and viral pathogens. In this review we consider three recurring themes of cytoskeletal involvement in bacterial pathogenesis: 1) the effect of bacterial toxins on actin-regulating small GTP-binding proteins; 2) the invasion of non phagocytic cells by the bacterial induction of ruffles at the plasma membrane; 3) the formation of actin tails and pedestals by intracellular and extracellular bacteria, respectively. Considerable progress has been made recently in the characterization of these processes. It is becoming clear that bacterial pathogens have developed a variety of sophisticated mechanisms for utilizing the complex cytoskeletal system of host cells. These bacterially-induced processes are now providing unique insights into the regulation of fundamental eukaryotic mechanisms. PMID- 11208092 TI - Facing inward from compartment shores: how many pathways were we looking for? AB - Protein toxins of the Shiga family have become potent tools in studying a number of intracellular transport events such as endocytosis, the communication between endosomes and the biosynthetic/secretory pathway, and retrograde transport from the Golgi apparatus to the endoplasmic reticulum. It seems clear today that most of these transport events can be explained from the toxins' interactions with cellular factors. This review will primarily focus on the discussion of recent data obtained on Shiga toxin and related toxins. We will point out to what extent the study of these proteins has opened new avenues for the development of intracellular targeting tools. PMID- 11208093 TI - Definition of distinct compartments in polarized Madin-Darby canine kidney (MDCK) cells for membrane-volume sorting, polarized sorting and apical recycling. AB - Previous studies of fibroblasts have demonstrated that recycling of endocytic receptors occurs through a default mechanism of membrane-volume sorting. Epithelial cells require an additional level of polar membrane sorting, but there are conflicting models of polar sorting, some suggesting that it occurs in early endosomes, others suggesting it occurs in a specialized apical recycling endosome (ARE). The relationship between endocytic sorting to the lysosomal, recycling and transcytotic pathways in polarized cells was addressed by characterizing the endocytic itineraries of LDL, transferrin (Tf) and IgA, respectively, in polarized Madin-Darby canine kidney (MDCK) cells. Quantitative analyses of 3 dimensional images of living and fixed polarized cells demonstrate that endocytic sorting occurs sequentially. Initially internalized into lateral sorting endosomes, Tf and IgA are jointly sorted from LDL into apical and medical recycling endosomes, in a manner consistent with default sorting of membrane from volume. While Tf is recycled to the basolateral membrane from recycling endosomes, IgA is sorted to the ARE prior to apical delivery. Quantifications of the efficiency of sorting of IgA from Tf between the recycling endosomes and the ARE match biochemical measurements of transepithelial protein transport, indicating that all polar sorting occurs in this step. Unlike fibroblasts, rab11 is not associated with Tf recycling compartments in either polarized or glass grown MDCK cells, rather it is associated with the compartments to which IgA is directed after sorting from Tf. These results complicate a suggested homology between the ARE and the fibroblast perinuclear recycling compartment and provide a framework that justifies previous conflicting models of polarized sorting. PMID- 11208094 TI - Adipsin and the glucose transporter GLUT4 traffic to the cell surface via independent pathways in adipocytes. AB - Insulin increases the exocytosis of many soluble and membrane proteins in adipocytes. This may reflect a general effect of insulin on protein export from the trans Golgi network. To test this hypothesis, we have compared the trafficking of the secreted serine protease adipsin and the integral membrane proteins GLUT4 and transferrin receptors in 3T3-L1 adipocytes. We show that adipsin is secreted from the trans Golgi network to the endosomal system, as ablation of endosomes using transferrin-HRP conjugates strongly inhibited adipsin secretion. Phospholipase D has been implicated in export from the trans Golgi network, and we show that insulin stimulates phospholipase D activity in these cells. Inhibition of phospholipase D action with butan-1-ol blocked adipsin secretion and resulted in accumulation of adipsin in trans Golgi network-derived vesicles. In contrast, butan-1-ol did not affect the insulin-stimulated movement of transferrin receptors to the plasma membrane, whereas this was abrogated following endosome ablation. GLUT4 trafficking to the cell surface does not utilise this pathway, as insulin-stimulated GLUT4 translocation is still observed after endosome ablation or inhibition of phospholipase D activity. Immunolabelling revealed that adipsin and GLUT4 are predominantly localised to distinct intracellular compartments. These data suggest that insulin stimulates the activity of the constitutive secretory pathway in adipocytes possibly by increasing the budding step at the TGN by a phospholipase D-dependent mechanism. This may have relevance for the secretion of other soluble molecules from these cells. This is not the pathway employed to deliver GLUT4 to the plasma membrane, arguing that insulin stimulates multiple pathways to the cell surface in adipocytes. PMID- 11208095 TI - MHC class II presentation of endogenous tumor antigen by cellular vaccines depends on the endocytic pathway but not H2-M. AB - We have developed cell-based cancer vaccines that activate anti-tumor immunity by directly presenting endogenously synthesized tumor antigens to CD4+ T helper lymphocytes via MHC class II molecules. The vaccines are non-conventional antigen presenting cells because they express MHC class II, do not express invariant chain or H-2M, and preferentially present endogenous antigen. To further improve therapeutic efficacy we have studied the intracellular trafficking pathway of MHC class II molecules in the vaccines using endoplasmic reticulumlocalized lysozyme as a model antigen. Experiments using endocytic and cytosolic pathway inhibitors (chloroquine, primaquine, and brefeldin A) and protease inhibitors (lactacystin, LLnL, E64, and leupeptin) indicate antigen presentation depends on the endocytic pathway, although antigen degradation is not mediated by endosomal or proteasomal proteases. Because H2-M facilitates presentation of exogenous antigen via the endocytic pathway, we investigated whether transfection of vaccine cells with H 2M could potentiate endogenous antigen presentation. In contrast to its role in conventional antigen presentation, H-2M had no effect on endogenous antigen presentation by vaccine cells or on vaccine efficacy. These results suggest that antigen/MHC class II complexes in the vaccines may follow a novel route for processing and presentation and may produce a repertoire of class II-restricted peptides different from those presented by professional APC. The therapeutic efficacy of the vaccines, therefore, may reside in their ability to present novel tumor peptides, consequently activating tumor-specific CD4+ T cells that would not otherwise be activated. PMID- 11208096 TI - Actin assembly plays a variable, but not obligatory role in receptor-mediated endocytosis in mammalian cells. AB - Three cell-permeant compounds, cytochalasin D, latrunculin A and jasplakinolide, which perturb intracellular actin dynamics by distinct mechanisms, were used to probe the role of filamentous actin and actin assembly in clathrin-mediated endocytosis in mammalian cells. These compounds had variable effects on receptor mediated endocytosis of transferrin that depended on both the cell line and the experimental protocol employed. Endocytosis in A431 cells assayed in suspension was inhibited by latrunculin A and jaspiakinolide, but resistant to cytochalasin D, whereas neither compound inhibited endocytosis in adherent A431 cells. In contrast, endocytosis in adherent CHO cells was more sensitive to disruption of the actin cytoskeleton than endocytosis in CHO cells grown or assayed in suspension. Endocytosis in other cell types, including nonadherent K562 human erythroleukemic cells or adherent Cos-7 cells was unaffected by disruption of the actin cytoskeleton. While it remains possible that actin filaments can play an accessory role in receptor-mediated endocytosis, these discordant results indicate that actin assembly does not play an obligatory role in endocytic coated vesicle formation in cultured mammalian cells. PMID- 11208098 TI - The endoplasmic reticulum--structure and function (Bristol, September 20-22, 1999). PMID- 11208097 TI - Sec7p directs the transitions required for yeast Golgi biogenesis. AB - Endoplasmic reticulum (ER)-to-Golgi traffic in yeast proceeds by the maturation of membrane compartments from post-ER vesicles to intermediate small vesicle tubular clusters (VTCs) to Golgi nodular membrane networks (Morin-Ganet et al., Traffic 2000; 1: 56-68). The balance between ER and Golgi compartments is maintained by COPII- and COPI-mediated anterograde and retrograde traffic, which are dependent on Sec7p and ARF function. The sec7-4 temperature-sensitive allele is a mutation in the highly conserved Sec7 domain (Sec7d) found in all ARF guanine nucleotide exchange factor proteins. Post-ER trafficking is rapidly inactivated in sec7-4 mutant yeast at the restrictive temperature. This conditional defect prevented the normal production of VTCs and instead generated Golgi-like tubes emanating from the ER exit sites. These tubes progressively developed into stacked cisternae defining the landmark sec7 mutant phenotype. Consistent with the in vivo results, a Sec7d peptide inhibited ER-to-Golgi transport and displaced Sec7p from its membrane anchor in vitro. The similarities in the consequences of inactivating Sec7p or ARFs in vivo was revealed by genetic disruption of yeast ARFs or by addition of brefeldin A (BFA) to whole cells. These treatments, as in sec7-4 yeast, affected the morphology of membrane compartments in the ER-Golgi transition. Further evidence for Sec7p involvement in the transition for Golgi biogenesis was revealed by in vitro binding between distinct domains of Sec7p with ARFs, COPI and COPII coat proteins. These results suggest that Sec7p coordinates membrane transitions in Golgi biogenesis by directing and scaffolding the binding and disassembly of coat protein complexes to membranes, both at the VTC transition from ER exit sites to form Golgi elements and for later events in Golgi maturation. PMID- 11208099 TI - Transport of proteins and membrane in eukaryotic cells (Gottingen, September 29 October 1, 1999). PMID- 11208100 TI - Second international workshop on antigen processing and presentation (Bar Harbor, October 16-18, 1999). PMID- 11208101 TI - Getting stuck in the Golgi. PMID- 11208102 TI - Lipid metabolism and regulation of membrane trafficking. AB - The past 20 years have witnessed tremendous progress in our understanding of the molecular machinery that controls protein and membrane transport between organelles (Scheckman R, Orci L. Coat proteins and vesicle budding. Science 1996;271: 1526-1533 and Rothman JE. Mechanisms of intracellular protein transport. Nature 1994;372: 55-63.) The research efforts responsible for these impressive advances have largely focused on the identification and characterization of protein factors that participate in membrane trafficking events. The role of membranes and their lipid constituents has received considerably less attention. Indeed, until rather recently, popular models for mechanisms of membrane trafficking had relegated membrane lipids to the status of a passive platform, subject to deformation by the action of coat proteins whose polymerization and depolymerization govern vesicle budding and fusion reactions. The 1990s, and particularly its last half, has brought fundamental reappraisals of the interface of lipids and lipid metabolism in regulating intracellular membrane trafficking events. Some of the emerging themes are reviewed here. PMID- 11208103 TI - Role of membrane organization and membrane domains in endocytic lipid trafficking. AB - Lipid compositions vary greatly among organelles, and specific sorting mechanisms are required to establish and maintain these distinct compositions. In this review, we discuss how the biophysical properties of the membrane bilayer and the chemistry of individual lipid molecules play a role in the intracellular trafficking of the lipids themselves, as well as influencing the trafficking of transmembrane proteins. The large diversity of lipid head groups and acyl chains lead to a variety of weak interactions, such as ionic and hydrogen bonding at the lipid/water interfacial region, hydrophobic interactions, and van-der-Waals interactions based on packing density. In simple model bilayers, these weak interactions can lead to large-scale phase separations, but in more complex mixtures, which mimic cell membranes, such phase separations are not observed. Nevertheless, there is growing evidence that domains (i.e., localized regions with non-random lipid compositions) exist in biological membranes, and it is likely that the formation of these domains are based on interactions similar to those that lead to phase separations in model systems. Sorting of lipids appears to be based in part on the inclusion or exclusion of certain types of lipids in vesicles or tubules as they bud from membrane organelles. PMID- 11208104 TI - Caveolins and cellular cholesterol balance. AB - Caveolins are major integral membrane components of caveolae. Over the last few years, evidence has accumulated for a close link between caveolin, caveolae, and the regulation of cellular cholesterol levels. However, the exact role of caveolin in this process, the intracellular trafficking routes followed by caveolin/cholesterol complexes, and the relationship of caveolin-cholesterol to other caveolin-mediated processes such as signal transduction have remained unclear. Recent findings from a number of systems suggest that specific signaling pathways require precise regulation of cellular cholesterol. Here we review evidence for caveolin regulation of cholesterol transport and consider how this may relate to signal transduction. PMID- 11208105 TI - Niemann-Pick type C mutations cause lipid traffic jam. AB - The Niemann-Pick C protein (NPC1) is required for cholesterol transport from late endosomes and lysosomes to other cellular membranes. Mutations in NPC1 cause lysosomal lipid storage and progressive neurological degeneration. Cloning of the NPC1 gene has given us tools with which to investigate the function of this putative cholesterol transporter. Here, we discuss recent studies indicating that NPC1 is not a cholesterol-specific transport molecule. Instead, NPC1 appears to be required for the vesicular shuttling of both lipids and fluid-phase constituents from multivesicular late endosomes to destinations such as the trans Golgi network. PMID- 11208106 TI - Lipid traffic: the ABC of transbilayer movement. AB - Membrane lipids do not spontaneously exchange between the two leaflets of lipid bilayers because the polar headgroups cannot cross the hydrophobic membrane interior. Cellular membranes, notably eukaryotic plasma membranes, are equipped with special proteins that actively translocate lipids from one leaflet to the other. In addition, cellular membranes contain proteins that facilitate a passive equilibration of lipids between the two membrane halves. In recent years, a growing number of proteins have been put forward as lipid translocators or facilitators. Unexpectedly, some of these appear to be required for efficient translocation of lipids lacking bulky headgroups, like cholesterol and fatty acids. The candidate lipid translocators identified so far belong to large protein families whose other members include pumps for amphiphilic molecules like bile salts and drugs. PMID- 11208107 TI - Trafficking and release of mycobacterial lipids from infected macrophages. AB - Analysis of infected macrophages revealed that lipid-containing moieties of the mycobacterial cell wall are actively trafficked out of the mycobacterial vacuole. To facilitate the analysis of vesicular trafficking from mycobacteria-containing phagosomes, surface-exposed carbohydrates were labeled with hydrazide-tagged markers. The distribution of labeled carbohydrate/lipid moieties and subsequent interaction with cellular compartments were analyzed by immunoelectron microscopy and by fluorescence microscopy of live cells. The released mycobacterial constituents were associated with several intracellular organelles and were enriched strikingly in tubular endocytic compartments. Subcellular fractionation of infected macrophages by density gradient electrophoresis showed temporal movement of labeled bacterial constituents through early and late endosomes. Thin layer chromatography analysis of these subcellular fractions confirmed their lipid nature and revealed five dominant bacteria-derived species. These mycobacterial lipids were also found in extracellular vesicles isolated from the medium and could be observed in un-infected 'bystander' cells. Their transfer to bystander cells could expand the bacteria's sphere of influence beyond the immediate confines of the host cell. PMID- 11208109 TI - Pep12p is a multifunctional yeast syntaxin that controls entry of biosynthetic, endocytic and retrograde traffic into the prevacuolar compartment. AB - Delivery of proteins to the vacuole of the yeast Saccharomyces cerevisiae requires the function of the endosomal syntaxin, Pep12p. Many vacuolar proteins, such as the soluble vacuolar hydrolase, carboxypeptidase Y (CPY), traverse the prevacuolar compartment (PVC) en route to the vacuole. Here we show that deletion of the carboxy-terminal transmembrane domain of Pep12p results in a temperature conditional block in transport of CPY to the PVC. The PVC also receives traffic from the early endosome and the vacuole, and mutation in PEP12 also blocks these other trafficking pathways into the PVC. Therefore, Pep12p is a multifunctional syntaxin that is required for all known trafficking pathways into the yeast PVC. Finally, we found that the internalized pheromone receptor, Ste3p, can cycle out of the PVC in a VPS27-independent fashion. PMID- 11208108 TI - Mammalian tumor susceptibility gene 101 (TSG101) and the yeast homologue, Vps23p, both function in late endosomal trafficking. AB - The mammalian tumor susceptibility gene tsg101 encodes the homologue of Vps23p, a class E Vps protein essential for normal membrane trafficking in the late endosome/multivesicular body of yeast. Both proteins assemble into large (approximately 350 kDa) cytosolic protein complexes and we show that the yeast complex contains another class E Vps protein, Vps28p. tsg101 mutant cells exhibit defects in sorting and proteolytic maturation of the lysosomal hydrolase cathepsin D, as well as in the steady-state distribution of the mannose-6 phosphate receptor. Additionally, endocytosed EGF receptors that are normally sorted to the lysosome are instead rapidly recycled back to the cell surface in tsg101 mutant cells. We propose that tsg101 mutant cells are defective in the delivery of cargo proteins to late endosomal compartments. One consequence of this endosomal trafficking defect is the delayed down-regulation/degradation of activated cell surface receptors, resulting in prolonged signaling. This may contribute to the tumorigenic phenotype exhibited by the tsg101 mutant fibroblasts. PMID- 11208110 TI - A new functional domain of guanine nucleotide dissociation inhibitor (alpha-GDI) involved in Rab recycling. AB - Guanine nucleotide dissociation inhibitor (GDI) is a 55-kDa protein that functions in vesicular membrane transport to recycle Rab GTPases. We have now determined the crystal structure of bovine alpha-GDI at ultra-high resolution (1.04 A). Refinement at this resolution highlighted a region with high mobility of its main-chain residues. This corresponded to a surface loop in the primarily alpha-helical domain II at the base of alpha-GDI containing the previously uncharacterized sequence-conserved region (SCR) 3A. Site-directed mutagenesis showed that this mobile loop plays a crucial role in binding of GDI to membranes and extraction of membrane-bound Rab. This domain, referred to as the mobile effector loop, in combination with Rab-binding residues found in the multi-sheet domain I at the apex of alpha-GDI may provide flexibility for recycling of diverse Rab GTPases. We propose that conserved residues in domains I and II synergize to form the functional face of GDI, and that domain II mediates a critical step in Rab recycling during vesicle fusion. PMID- 11208111 TI - A screen of random sequences for those that alter the trafficking of the influenza virus hemagglutinin in vivo. AB - In order to determine if the sequence patterns known to specify internalization represent the majority of possible internalization signals, we identified random sequences capable of causing a reporter protein to be internalized at least several-fold faster than the rate of non-selective internalization of membrane by clathrin-coated pits. A library of influenza hemagglutinin (HA) proteins, bearing short random sequences in place of the wild-type cytoplasmic domain, was prepared in recombinant SV40 virus. The library was expressed and screened for HAs that could internalize anti-HA antibody from the medium. The cytoplasmic sequences of the selected proteins were determined. From a small sample of sequences we detected several that did not resemble those previously identified. The known internalization signals must represent only a subset of the sequences that can serve as internalization signals. PMID- 11208112 TI - When cell biology grew up. PMID- 11208113 TI - Pathways for lipid antigen presentation by CD1 molecules: nowhere for intracellular pathogens to hide. AB - A crucial feature of peptide antigen presentation by major histocompatibility complex (MHC) class I and II molecules is their differential ability to sample cytosolic and extracellular antigens. Intracellular viral infections and bacteria that are taken up in phagosomes, but then escape from the endocytic compartment efficiently, enter the class I pathway via the cytosol. In contrast, phagosome resident bacteria yield protein antigens that are sampled deep in the endocytic compartment and presented in a vacuolar acidification-dependent pathway mediated by MHC class II molecules. Despite this potential for antigen sampling, microbes have evolved a variety of evasive mechanisms that affect peptide transport in the MHC class I pathway or blockade of endosomal acidification and inhibition of phagosome-lysosome fusion that may compromise the MHC class II pathway of antigen presentation. Thus, besides MHC class I and II, a third lineage of antigen presenting molecules that bind lipid and glycolipid antigens rather than peptides exists and is mediated by the family of CD1 proteins. CD1 isoforms (CD1a, b, c, and d) differentially sample both recycling endosomes of the early endocytic system and late endosomes and lysosomes to which lipid antigens are differentially delivered. These CD1 pathways include vacuolar acidification independent pathways for lipid antigen presentation. These features of presenting lipid antigens, independently monitoring various antigen-containing intracellular compartments and avoiding certain evasive techniques employed by microbes, enable CD1 molecules to provide distinct opportunities to function in host defense against the microbial world. PMID- 11208114 TI - Intracellular surveillance: controlling the assembly of MHC class I-peptide complexes. AB - MHC class I molecules bind with high affinity to peptides in the endoplasmic reticulum and display them on the cell surface. Here they are screened by CD8 positive T-lymphocytes for the presence of foreign, pathogen-derived peptides within the mass of self-peptides expressed. MHC class I assembly is a complicated process involving a number of accessory molecules, including specialized components as well as common chaperones. Our understanding of the mechanisms involved, while quite advanced, is far from complete. PMID- 11208115 TI - Control of MHC class I traffic from the endoplasmic reticulum by cellular chaperones and viral anti-chaperones. AB - MHC class I molecules assemble with peptides in the endoplasmic reticulum (ER). To ensure that only peptide-loaded MHC molecules leave the ER, empty molecules are retained by ER-resident chaperones, most notably the MHC-specific tapasin. ER exit of class I MHC is also controlled by viruses, but for the opposite purpose of preventing peptide presentation to T cells. Interestingly, some viral proteins are able to retain MHC class I molecules in the ER despite being transported. By contrast, other viral proteins exit the ER only upon binding to class I MHC, thereby rerouting newly synthesized class I molecules to intracellular sites of proteolysis. Thus, immune escape can be achieved by reversing, inhibiting or redirecting the chaperone-assisted MHC class I folding, assembly and intracellular transport. PMID- 11208116 TI - Antigen traffic pathways in dendritic cells. AB - Dendritic cells (DC) are now believed to be the principal initiators of T cell mediated immune responses. Their location in body tissues, migratory behaviour in response to inflammatory stimuli, endocytic properties, expression of MHC molecules and key T cell stimulatory molecules and many other attributes place these remarkable cells in a unique and influential position in the immune system. Progress in DC culture methods has recently allowed in-depth studies on the cell biological features that enable them to fulfill their crucial role in the immune response. PMID- 11208118 TI - Role of cholesterol in developing T-tubules: analogous mechanisms for T-tubule and caveolae biogenesis. AB - Recent work has suggested that caveolae biogenesis and transverse-tubule (T tubule) formation in muscle cells share similar underlying features. We compared the properties of caveolin-1 (cav-1)-positive caveolae, in epithelial cells, with caveolin-3 (cav-3)-positive precursor T-tubules, in differentiating C2C12 muscle cells, using the cholesterol-binding drug, Amphotericin B (AmphB). Treatment of MDCK epithelial cells with acute high doses or chronic low doses of AmphB caused a loss of surface caveolae and the rapid redistribution of cav-1, and exogenously expressed cav-3, from the cell surface into modified endosomes. This effect was reversible and specific, as the GPI-anchored protein, alkaline phosphatase, was largely unaffected by the treatment unless it had been previously partitioned into caveolar domains. In differentiating C2C12 mouse myotubes, AmphB also caused a complete redistribution of cav-3 from precursor T-tubule elements into enlarged endosomes, morphologically very similar to those seen in MDCK cells. This was accompanied by redistribution of a T-tubule marker and a dramatic reduction in the extent of surface-connected tubular elements. We propose that cholesterol enriched glycolipid 'raft' domains are involved in the formation and maintenance of diverse membrane systems including caveolae and the T-tubule system of muscle. PMID- 11208117 TI - Human cytomegalovirus immediate early glycoprotein US3 retains MHC class I molecules by transient association. AB - Human cytomegalovirus (HCMV) interferes with major histocompatibility complex (MHC) class I antigen presentation by a sequential multistep process to escape T cell surveillance. During the immediate early phase of infection, the glycoprotein US3 prevents intracellular transport of MHC class I molecules. Interestingly, US3 displays a significantly shorter half-life than US3-retained MHC class I molecules. Here we show that US3 associates only transiently with MHC class I molecules, exits the ER, and is inefficiently retrieved from the Golgi. US3 was degraded in a post-Golgi compartment, most likely lysosomes, because: i) Brefeldin A treatment prolonged the half-life of US3; and ii) US3 co-localized with the lysosomal marker protein LAMP in chloroquine-treated cells. In contrast, MHC class I molecules remained stable in the ER. Upon inhibition of protein synthesis MHC class I molecules were released suggesting that a continuous supply of newly synthesized US3 molecules is required for inhibition of transport. Thus, US3 does not seem to retain MHC class I molecules by a retrieval mechanism. Instead, our observations are consistent with US3 preventing MHC class I trafficking by blocking forward transport. PMID- 11208119 TI - Coatomer vesicles are not required for inhibition of Golgi transport by G-protein activators. AB - The G-protein activators guanosine 5'-O-(3-thiodiphosphate) (GTP gamma S) and aluminum fluoride (AIF) are thought to inhibit transport between Golgi cisternae by causing the accumulation of nonfunctional coatomer-coated transport vesicles on the Golgi. Although GTP gamma S and AIF inhibit transport in cell-free intra Golgi transport systems, blocking coatomer vesicle formation does not. We therefore determined whether inhibition of in vitro Golgi transport by these agents requires coatomer vesicle formation. Depletion of coatomer was found to completely block coated vesicle formation on Golgi cisternae without affecting inhibition of in vitro transport by either GTP gamma S or AIF. Depletion of ADP ribosylation factor (ARF) prevented inhibition of transport by GTP gamma S, but not by AIF, suggesting that the AIF-sensitive component in transport may not be a GTP-binding protein. Surprisingly, depletion of cytosolic ARF did not prevent the GTP gamma S-induced formation of Golgi-coated vesicles, whereas ARF was required for AIF-induced vesicle formation. Although ARF or coatomer depletion caused an increase in the fenestration of cisternae, no other ultrastructural changes were observed that might explain the inhibition of transport by GTP gamma S or AIF. These findings suggest that ARF-GTP gamma S and AIF act by distinct and coatomer independent mechanisms to inhibit membrane fusion in cell-free intra-Golgi transport. PMID- 11208120 TI - Targeting of an apical endosomal protein to endosomes in Madin-Darby canine kidney cells requires two sorting motifs. AB - The efficient sorting and targeting of endocytosed macromolecules is critical for epithelial function. However, the distribution of endosomal compartments in these cells remains controversial. In this study, we show that polarized Madin-Darby canine kidney (MDCK) cells target the apical endosomal protein endotubin into an apical early endosomal compartment that is distinct from the apical recycling endosomes. Furthermore, through a panel of site-directed mutations we show that signals required for apical endosomal targeting of endotubin are composed of two distinct motifs on the cytoplasmic domain, a hydrophobic motif and a consensus casein kinase II site. Endotubin-positive endosomes in MDCK cells do not label with basolaterally internalized transferrin or ricin, do not contain the small guanosine triphosphate-binding protein rab11, and do not tubulate in response to low concentrations of brefeldin-A (BFA). Nevertheless, high concentrations of BFA reversibly inhibits the sorting of endotubin from transferrin and cause colocalization in tubular endosomes. These results indicate that, in polarized cells, endotubin targets into a distinct subset of apical endosomes, and the targeting information required both for polarity and endosomal targeting is provided by the cytoplasmic portion of the molecule. PMID- 11208121 TI - Are the curves in all the right places? PMID- 11208122 TI - Traffic COPs of the early secretory pathway. AB - Intracellular transport between the endoplasmic reticulum and Golgi compartments is mediated by coat protein complexes (COPI and COPII) that form transport vesicles and collect the desired set of cargo. Although the COPI and COPII coats are molecularly distinct, a number of mechanistic parallels appear to be emerging, most notably a general role for small guanine triphosphatases in co ordinating coat assembly with cargo selection. A combination of morphological, biochemical, and genetic methods is revealing a very dynamic relationship between these compartments, and highlights a central role for COPs in directing traffic through the early secretory pathway. This review focuses on recent advances in molecular mechanisms underlying coated-vesicle assembly and connections with cellular structures. PMID- 11208123 TI - Selective inhibition of adaptor complex-mediated vesiculation. AB - A short while ago, we could only inhibit post-Golgi membrane traffic with crude, unselective tools, such as low temperature or high extracellular sucrose. Molecular dissection of vesiculation steps has revealed unexpected complexity in the coating machinery that has initiated a search for more specific inhibitors. We have learned that membrane vesiculation is driven by a tightly regulated multicomponent, membrane-associated protein machine held together by carefully specified interaction domains. An experimental advantage of such complex interacting machinery is that it is very susceptible to disruption by dominant negative inhibitors or by overexpression. As a result, we now have much more specific inhibitors of post-Golgi membrane traffic. Some, such as dynamin K44A, may be general inhibitors, whereas others can distinguish classes of endocytotic events (10), binding events that require clathrin from those that do not (42), or specific steps of endocytosis (62). Ligand-mediated uptake of EGF and numerous, but not all, GPCRs can be inhibited by overexpression of an ARF GTPase-activating protein that has no effect on transferrin uptake (67). We can look forward to increasingly powerful and selective inhibitors that should help us to navigate successfully the complex routes of post-Golgi membrane traffic. PMID- 11208124 TI - Garrotes, springs, ratchets, and whips: putting dynamin models to the test. AB - The GTPase dynamin is essential for clathrin-mediated endocytosis. Numerous new and exciting discoveries regarding dynamin function in vivo and in vitro have led to various models in which dynamin functions directly in membrane fission and the release of clathrin-coated vesicles from the plasma membrane. This would make dynamin unique among GTPases in its ability to act as a mechanochemical enzyme. Here we review the various models and their supporting data. We then discuss new findings that raise doubts as to whether dynamin breaks the paradigm that governs regulatory GTPases. PMID- 11208125 TI - Molecular structures of proteins involved in vesicle coat formation. AB - This review includes 16 structures of vesicle coat components and accessory proteins and a description of their roles in vesicle budding or coat disassembly. PMID- 11208126 TI - The tail domain of myosin M catalyses nucleotide exchange on Rac1 GTPases and can induce actin-driven surface protrusions. AB - Members of the myosin superfamily play crucial roles in cellular processes including management of the cortical cytoskeleton, organelle transport and signal transduction. GTPases of the Rho family act as key control elements in the reorganization of the actin cytoskeleton in response to growth factors, and other functions such as membrane trafficking, transcriptional regulation, growth control and development. Here, we describe a novel unconventional myosin from Dictyostelium discoideum, MyoM. Primary sequence analysis revealed that it has the appearance of a natural chimera between a myosin motor domain and a guanine nucleotide exchange factor (GEF) domain for Rho GTPases. The functionality of both domains was established. Binding of the motor domain to F-actin was ATP dependent and potentially regulated by phosphorylation. The GEF domain displayed selective activity on Rac1-related GTPases. Overexpression, rather than absence of MyoM, affected the cell morphology and viability. Particularly in response to hypo-osmotic stress, cells overexpressing the MyoM tail domain extended massive actin-driven protrusions. The GEF was enriched at the tip of growing protuberances, probably through its pleckstrin homology domain. MyoM is the first unconventional myosin containing an active Rac-GEF domain, suggesting a role at the interface of Rac-mediated signal transduction and remodeling of the actin cytoskeleton. PMID- 11208127 TI - Truncated brush border myosin I affects membrane traffic in polarized epithelial cells. AB - We investigate, in this study, the potential involvement of an acto-myosin-driven mechanism in endocytosis of polarized cells. We observed that depolymerization of actin filaments using latrunculin A decreases the rate of transferrin recycling to the basolateral plasma membrane of Caco-2 cells, and increases its delivery to the apical plasma membrane. To analyze whether a myosin was involved in endocytosis, we produced, in this polarized cell line, truncated, non-functional, brush border, myosin I proteins (BBMI) that we have previously demonstrated to have a dominant negative effect on endocytosis of unpolarized cells. These non functional proteins affect the rate of transferrin recycling and the rate of transepithelial transport of dipeptidyl-peptidase IV from the basolateral plasma membrane to the apical plasma membrane. They modify the distribution of internalized endocytic tracers in apical multivesicular endosomes that are accessible to fluid phase tracers internalized from apical and basolateral plasma membrane domains. Altogether, these observations suggest that an acto-myosin driven mechanism is involved in the trafficking of basolaterally internalized molecules to the apical plasma membrane. PMID- 11208128 TI - A novel pathway for transport and metabolism of a fluorescent phosphatidic acid analog in yeast. AB - Phosphatidic acid is a central intermediate of biosynthetic lipid metabolism as well as an important signaling molecule in the cell. These studies assess the internalization, or retrograde transport, and metabolism of phosphatidic acid in yeast using a fluorescent analog. An analog of phosphatidic acid fluorescently labeled at the sn-2 position with N-4-nitrobenz-2-oxa-1, 3-diazole-aminocaproic acid (NBD-phosphatidic acid) was introduced to yeast cells by spontaneous transfer from phospholipid vesicles. Transport and metabolism of the NBD phosphatidic acid were then monitored by fluorescence spectrophotometry, fluorescence microscopy and routine biochemical methods. Primary metabolites of the NBD-phosphatidic acid in yeast were found to be NBD-diacylgycerol and NBD phosphatidylinositol. Experiments in cells possessing different levels of phosphatidate phosphatase activity suggest that conversion of the NBD phosphatidic acid to NBD-diacylglycerol is not a pre-requisite for internalization in yeast. Internalization is sensitive to decreased temperature, but neither ATP depletion nor a sec6-4 mutation, which interrupts endocytosis, has an affect. Thus, internalization of NBD-phosphatidic acid apparently occurs via a non-endocytic route. These characteristics of retrograde transport of NBD phosphatidic acid in yeast differ significantly from transport of other NBD phospholipids in yeast as well as NBD-phosphatidic acid transport in mammalian fibroblasts. PMID- 11208129 TI - Secretory lysosome biogenesis in cytotoxic T lymphocytes from normal and Chediak Higashi syndrome patients. AB - The lytic proteins mediating target cell killing are stored in the lysosomes of activated cytotoxic T lymphocytes (CTL) and are secreted upon recognition of a target cell. These secretory lysosomes cannot be detected in resting T lymphocytes. Interaction of a resting cell with a target cell activates de novo formation of secretory lysosomes. CTL clones in culture mimic this behaviour, and so provide an ideal system for studying secretory lysosome biogenesis and maturation. In the genetic disease, Chediak Higashi syndrome (CHS), all lysosomes in the cells are enlarged and reduced in number compared with wild-type (WT) cells. We have used CTL from this disease to study secretory lysosome biogenesis and maturation. We show that at early stages after activation the secretory lysosomes are identical in WT and mutant cells, and that delivery of proteins to the secretory lysosome along the biosynthetic and endocytic pathways is normal in the mutant cells. With time, the lysosomes in the mutant cells aggregate, become larger and fewer in number and eventually form giant structures. Our results show that the initial steps of secretory lysosome formation are normal in CHS, but that the organelles subsequently fuse together during cell maturation to form the giant secretory lysosomes. PMID- 11208131 TI - The protein import machinery of the mitochondrial membranes. AB - Mitochondria are surrounded by two membranes that contain independent and non related protein transport machineries. Remarkable progress was recently achieved in elucidating the structure of the outer membrane import channel and in the identification of new components involved in protein traffic across the intermembrane space and the inner membrane. Traditional concepts of protein targeting and sorting had to be revised. Here we briefly summarize the data on the mitochondrial protein import system with particular emphasis on new developments and perspectives. PMID- 11208130 TI - The molecular mechanism of transport of macromolecules through nuclear pore complexes. AB - Trafficking of macromolecules between nuclear and cytoplasmic compartments takes place through the nuclear pore complexes (NPCs) of the nuclear envelope. Nuclear trafficking involves a complex series of interactions between cargo, soluble transport factors (carriers) and nuclear pore proteins (nucleoporins) that are orchestrated by the Ras-family GTPase Ran. The primary role of Ran is probably to establish directionality and to sort molecules to be transported by controlling the interaction between carriers and cargoes, so that they bind in one compartment but dissociate in the other. Translocation of carriers and cargo carrier complexes through NPCs requires interactions between the carriers and nucleoporins that contain distinctive tandem sequence repeats based on cores rich in glycine and phenylalanine residues that are separated by hydrophilic linkers. Much recent work has focused on these interactions and, in particular, their specificity, regulation and function. Evidence is accumulating that carriers move through the NPC by distinct but overlapping routes using specific subsets of nucleoporins. PMID- 11208132 TI - How peroxisomes arise. AB - Peroxisomes are formed by the synthesis and assembly of membrane proteins and lipids, the selective import of proteins from the cytosol, and the growth and division of resultant organelles. To date, 23 proteins, called peroxins, are known to participate in these processes. This review summarizes recent progress in peroxin characterization and examines the underlying molecular mechanisms of peroxisome biosynthesis. PMID- 11208133 TI - Molecular structures of proteins involved in vesicle fusion. AB - We present a summary of the structures of 13 proteins involved in the docking and fusion of intracellular transport vesicles to their target membranes. PMID- 11208134 TI - Apical and basolateral endocytic pathways of MDCK cells meet in acidic common endosomes distinct from a nearly-neutral apical recycling endosome. AB - Quantitative confocal microscopic analyses of living, polarized MDCK cells demonstrate different pH profiles for apical and basolateral endocytic pathways, despite a rapid and extensive intersection between the two. Three-dimensional characterizations of ligand trafficking demonstrate that the apical and basolateral endocytic pathways share early, acidic compartments distributed throughout the medial regions of the cell. Polar sorting for both pathways occurs in these common endosomes as IgA is sorted from transferrin to alkaline transcytotic vesicles. While transferrin is directly recycled from the common endosomes, IgA is transported to a downstream apical compartment that is nearly neutral in pH. By several criteria this compartment appears to be equivalent to the previously described apical recycling endosome. The functional significance of the abrupt increase in lumenal pH that accompanies IgA sorting is not clear, as disrupting endosome acidification has no effect on polar sorting. These studies provide the first detailed characterizations of endosome acidification in intact polarized cells and clarify the relationship between the apical and basolateral endocytic itineraries of polarized MDCK cells. The extensive mixing of apical and basolateral pathways underscores the importance of endocytic sorting in maintaining the polarity of the plasma membrane of MDCK cells. PMID- 11208135 TI - Both calmodulin and the unconventional myosin Myr4 regulate membrane trafficking along the recycling pathway of MDCK cells. AB - In epithelial cells, endocytosed transferrin and its receptor, which cycle basolaterally, have been shown to transit through recycling endosomes which can also be accessed by markers internalized from the apical surface. In this work, we have used an in vitro assay to follow transfer of an endocytosed marker from apical or basolateral early endosomes to recycling endosomes labeled with transferrin. We show that calmodulin (CaM) function is necessary for transfer and identified myr4, a member of the unconventional myosin superfamily known to use CaM as a light chain, as a possible target protein for CaM. Since myr4 is believed to act as an actin-based mechanoenzyme, we tested the role of polymerized actin in the assay. Our data show that conditions which either prevent actin polymerization or induce the breakdown of existing filaments strongly inhibit interactions between recycling endosomes and either set of early endosomes. Altogether, our data indicate that trafficking at early steps of the endocytic pathway in Madin-Darby Canine Kidney cells depends on the actin-based mechanoenzyme myr4, its light chain CaM, and polymerized actin. PMID- 11208136 TI - Phospholipase A2 antagonists inhibit constitutive retrograde membrane traffic to the endoplasmic reticulum. AB - Eukaryotic cells contain a variety of cytoplasmic Ca(2+)-dependent and Ca(2+) independent phospholipase A2s (PLA2s; EC 2.3.1.2.3). However, the physiological roles for many of these ubiquitously-expressed enzymes is unclear or not known. Recently, pharmacological studies have suggested a role for Ca(2+)-independent PLA2 (iPLA2) enzymes in governing intracellular membrane trafficking events in general and regulating brefeldin A (BFA)-stimulated membrane tubulation and Golgi to-endoplasmic reticulum (ER) retrograde membrane trafficking, in particular. Here, we extend these studies to show that membrane-permeant iPLA2 antagonists potently inhibit the normal, constitutive retrograde membrane trafficking from the trans-Golgi network (TGN), Golgi complex, and the ERGIC-53-positive ER-Golgi intermediate compartment (ERGIC), which occurs in the absence of BFA. Taken together, these results suggest that iPLA2 enzymes play a general role in regulating, or directly mediating, multiple mammalian membrane trafficking events. PMID- 11208137 TI - A functional role for VAP-33 in insulin-stimulated GLUT4 traffic. AB - Soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNAREs) are critical proteins in membrane fusion, in both regulated and constitutive vesicular traffic. In addition, proteins that interact with the SNAREs are thought to regulate fusion. Vesicle-associated membrane protein-2 (VAMP-2) is a SNARE protein involved in insulin-dependent glucose transporter 4 (GLUT4) traffic. VAMP-2 is required for productive GLUT4 incorporation into the plasma membrane. VAMP-associated protein of 33 kDa (VAP-33) is an integral membrane protein that binds VAMPs in vitro, and is hypothesized to be a regulator of VAMPs. In L6 skeletal myoblasts, which display insulin-dependent traffic of GLUT4, we show that VAP-33 colocalized significantly with VAMP-2 using indirect confocal immunofluorescence and biochemical cosegregation. Overexpression of wild type VAP-33 in L6 myoblasts attenuated the insulin-dependent incorporation of myc tagged GLUT4 into the plasma membrane, and this response was restored by co overexpression of VAMP-2 linked to green fluorescent protein. Antibodies to VAP 33 microinjected into 3T3-L1 adipocytes abrogated the insulin-stimulated translocation of GLUT4 to the plasma membrane, as measured in adhered plasma membrane lawns. Immunopurified VAMP-2-containing compartments from L6 myotubes and 3T3-L1 adipocytes showed significant levels of VAP-33. We propose that VAP-33 may be a regulator of VAMP-2 availability for GLUT4 traffic and other vesicle fusion events. PMID- 11208138 TI - Occam's Razor slices through the mysteries of neurofilament axonal transport: can it really be so simple? PMID- 11208139 TI - Endocytosis in viral replication. AB - Although initially recognised as essential for the entry of certain viruses, endocytosis is now known to also play important roles in the replication of, and adaptation to, the host cell of a number of viruses. Here we consider several aspects of this association and recent results that have emerged to support this view. PMID- 11208140 TI - Folding of viral envelope glycoproteins in the endoplasmic reticulum. AB - Viral glycoproteins fold and oligomerize in the endoplasmic reticulum of the host cell. They employ the cellular machinery and receive assistance from cellular folding factors. During the folding process, they are retained in the compartment and their structural quality is checked by the quality control system of the endoplasmic reticulum. A special characteristic that distinguishes viral fusion proteins from most cellular proteins is the extensive conformational change they undergo during fusion of the viral and cellular membrane. Many viral proteins fold in conjunction with and dependent on a viral partner protein, sometimes even synthesized from the same mRNA. Relevant for folding is that viral glycoproteins from the same or related virus families may consist of overlapping sets of domain modules. The consequences of these features for viral protein folding are at the heart of this review. PMID- 11208141 TI - Role of P30 in replication and spread of TMV. AB - The P30 movement protein (MP) of tobacco mosaic virus is essential for distribution of sites of replication within infected cells and for cell-cell spread of infection. MP is an integral membrane protein and in early and mid stages of infection causes severe disruption of the cortical endoplasmic reticulum (ER). MP also associates with microtubules, and in late stages is targeted for degradation by the 26S proteosome. During these stages, the ER regains its normal pre-infection configuration. Viral RNA is associated with ER and microtubules in the presence of MP. The MP is phosphorylated and mutation of the phosphorylated amino acid reduced association of MP with the ER, plasmodesmata, and microtubules, and altered the stability of the MP. The nature of the association of MP with vRNA and ER and microtubules, and the role of phosphorylation of MP in each of these functions, if any, remains to be determined. PMID- 11208142 TI - The production of 'cell cortices' for light and electron microscopy. PMID- 11208143 TI - SNARE protein trafficking in polarized MDCK cells. AB - A key feature of polarized epithelial cells is the ability to maintain the specific biochemical composition of the apical and basolateral plasma membrane domains. This polarity is generated and maintained by the continuous sorting of apical and basolateral components in the secretory and endocytic pathways. Soluble N-ethyl maleimide-sensitive factor attachment protein receptors (SNARE) proteins of vesicle-associated membrane protein (VAMP) and syntaxin families have been suggested to play a role in the biosynthetic transport to the apical and basolateral plasma membranes of polarized cells, where they likely mediate membrane fusion. To investigate the involvement of SNARE proteins in membrane trafficking to the apical and basolateral plasma membrane in the endocytic pathway we have monitored the recycling of various VAMP and syntaxin molecules between intracellular compartments and the two plasma membrane domains in Madin Darby canine kidney (MDCK) cells. Here we show that VAMP8/endobrevin cycles through the apical but not through the basolateral plasma membrane. Furthermore, we found that VAMP8 localizes to apical endosomal membranes in nephric tubule epithelium and in MDCK cells. This asymmetry in localization and cycling behavior suggests that VAMP8/endobrevin may play a role in apical endosomal trafficking in polarized epithelium cells. PMID- 11208144 TI - Endocytic recycling is required for the presentation of an exogenous peptide via MHC class II molecules. AB - Exogenous antigenic peptides captured and presented in the context of major histocompatibility (MHC) class II molecules on APC, have been employed as potent vaccine reagents capable of activating cellular immune responses. Binding and presentation of select peptide via surface class II molecules has been reported. Here, a role for endocytosis and early endosomes in the presentation of exogenous peptides via MHC class II molecules is described. T cell recognition of a 14 amino acid human serum albumin-derived peptide in the context of HLA-DR4 was observed only with metabolically active APC. The delayed kinetics and temperature dependence of functional peptide presentation via APC, were consistent with a requirement for peptide internalization to early endosomal compartments prior to T cell recognition. Ablating endocytosis by exposing cells to inhibitors of ATP production completely blocked the display of functional peptide:class II complexes on the surface of the APC. Presentation of the peptide was also found to be sensitive to primaquine, a drug that perturbs the recycling of transport vesicles containing endocytic receptors and mature class II complexes. Functional presentation of the endocytosed peptide was dependent upon these mature class II complexes, as inhibitor studies ruled out a requirement for newly synthesized class II molecules. N-terminal processing of the endocytosed peptide was observed upon trafficking through endosomal compartments and linked to the formation of functional peptide:class II complexes. These findings establish a novel mechanism for regulating class II-restricted peptide presentation via the endocytic pathway. PMID- 11208146 TI - Membrane tethering and fusion in the secretory and endocytic pathways. AB - Studies of intracellular trafficking over the past decade or so have led to striking advances in our understanding of the molecular processes by which transport intermediates dock and fuse. SNARE proteins play a central role, assembling into complexes that bridge membranes and may catalyze membrane fusion directly. In general, different SNARE proteins operate in different intracellular trafficking pathways, so recent reports that SNARE assembly in vitro is promiscuous have come as something of a surprise. We propose a model in which proper SNARE assembly is under kinetic control, orchestrated by members of the Sec1 protein family, small GTP-binding Rab proteins, and a diverse assortment of tethering proteins. PMID- 11208145 TI - Regulation of lamp2a levels in the lysosomal membrane. AB - The selective degradation of cytosolic proteins in lysosomes by chaperone mediated autophagy depends, at least in part, on the levels of a substrate receptor at the lysosomal membrane. We have previously identified this receptor as the lysosome-associated membrane protein type 2a (lamp2a) and showed that levels of lamp2a at the lysosomal membrane directly correlate with the activity of the proteolytic pathway. Here we show that levels of lamp2a at the lysosomal membrane are mainly controlled by changes in its half-life and its distribution between the lysosomal membrane and the matrix. The lysosomal degradation of lamp2a requires the combined action of at least two different proteolytic activities at the lysosomal membrane. Lamp2a is released from the membrane by the action of these proteases, and then the truncated lamp2a is rapidly degraded within the lysosomal matrix. Membrane degradation of lamp2a is a regulated process that is inhibited in the presence of substrates for chaperone-mediated autophagy and under conditions that activate that type of autophagy. Uptake of substrate proteins also results in transport of some intact lamp2a from the lysosomal membrane into the matrix. This fraction of lamp2a can be reinserted back into the lysosomal membrane. The traffic of lamp2a through the lysosomal matrix is not mediated by vesicles, and lamp2a reinsertion requires the lysosomal membrane potential and protein components of the lysosomal membrane. The distribution of lamp2a between the lysosomal membrane and matrix is a dynamic process that contributes to the regulation of lysosomal membrane levels of lamp2a and consequently to the activity of the chaperone-mediated autophagic pathway. PMID- 11208147 TI - Membrane fusion mechanisms: the influenza hemagglutinin paradigm and its implications for intracellular fusion. AB - The mechanism of membrane fusion induced by the influenza virus hemagglutinin (HA) has been extensively characterized. Fusion is triggered by low pH, which induces conformational changes in the protein, leading to insertion of a hydrophobic 'fusion peptide' into the viral membrane and the target membrane for fusion. Insertion perturbs the target membrane, and hour glass-shaped lipidic fusion intermediates, called stalks, fusing the outer monolayers of the two membranes, are formed. Stalk formation is followed by complete fusion of the two membranes. Structures similar to those formed by HA at the pH of fusion are found not only in many other viral fusion proteins, but are also formed by SNAREs, proteins involved in intracellular fusion. Substances that inhibit or promote HA induced fusion because they affect stalk formation, also inhibit or promote intracellular fusion, cell-cell fusion and even intracellular fission similarly. Therefore, the mechanism of influenza HA-induced fusion may be a paradigm for many intracellular fusion events. PMID- 11208148 TI - Greasing membrane fusion and fission machineries. AB - Biological membrane fusion is a local-point event, extremely fast, and under strict control. Proteins are responsible for the mutual recognition of the fusion partners and for the initiation of biomembrane fusion, and thus determine where and when fusion occurs. However, the central event during membrane fusion is the merger of two membranes, which requires a transient reorganization of membrane lipids into highly curved fusion intermediates. This review focuses on the potential role of lipids in the generation of membrane curvature, and thus in the regulation of membrane fusion and fission. PMID- 11208149 TI - How to convert a traditional electron microscopy laboratory to digital imaging: follow the 'middle road'. AB - Today, electron microscopy (EM) is increasingly confronted by the revolution in image-processing technology provoked by modern computers. Digital cameras are fast replacing film-based cameras in EM, as elsewhere, and the procedures for digital image-archiving, image-analysis, and image publication are rapidly evolving. To take advantage of these advances, we have chosen for the moment a 'middle road', in which film remains our basic recording medium in the electron microscope, but immediately thereafter, all film-based images are converted to digital files for further analysis and processing. The rationale behind this approach is that film still offers far greater sensitivity and resolution (providing an image equivalent to > 10,000 pixels per inch in a 1-s exposure), and film is still far easier to organize and archive than digital images of comparable resolution. However, digital manipulation of EM images has become mandatory. Hence, we explain here, in some detail, how we convert from film to digital. PMID- 11208150 TI - Multiple local contact sites are induced by GPI-linked influenza hemagglutinin during hemifusion and flickering pore formation. AB - Membrane fusion intermediates induced by the glycosylphosphatidylinositol-linked ectodomain of influenza hemagglutinin (GPI-HA) were investigated by rapid freeze, freeze-substitution, thin section electron microscopy, and with simultaneous recordings of whole-cell admittance and fluorescence. Upon triggering, the previously separated membranes developed numerous hourglass shaped points of membrane contact (approximately 10-130 nm waist) when viewed by electron microscopy. Stereo pairs showed close membrane contact at peaks of complementary protrusions, arising from each membrane. With HA, there were fewer contacts, but wide fusion pores. Physiological measurements showed fast lipid dye mixing between cells after acidification, and either fusion pore formation or the lack thereof (true hemifusion). For the earliest pores, a similar conductance distribution and frequency of flickering pores were detected for both HA and GPI HA. For GPI-HA, lipid mixing was detected prior to, during, or after pore opening, whereas for HA, lipid mixing is seen only after pore opening. Our findings are consistent with a pathway wherein conformational changes in the ectodomain of HA pull membranes towards each other to form a contact site, then hemifusion and pore formation initiate in a small percentage of these contact sites. Finally, the transmembrane domain of HA is needed to complete membrane fusion for macromolecular content mixing. PMID- 11208151 TI - The dileucine motif within the tail of MPR46 is required for sorting of the receptor in endosomes. AB - The cytoplasmic tail of MPR46 carries a leucine-based motif that is required for the sorting of lysosomal enzymes by the receptor. In addition, it is one of three independent, but functionally redundant, internalization signals present in the cytoplasmic tail of MPR46. We have analyzed a mutant of MPR46, in which the dileucine pair was replaced by alanines (MPR46 LL/AA) with respect to its intracellular distribution and trafficking. Ultrastructural analysis of cells expressing the MPR46 LL/AA mutant revealed that the substitution of the dileucine pair causes a shift of the receptor distribution from the TGN, where it is packaged into AP1-containing vesicles, to vesicular structures distributed throughout the cytoplasm. The vesicles could be identified as early endosomes with internalized BSA-gold and rab5 as markers. By analyzing the receptor trafficking biochemically, we found that return of the LL/AA mutant receptor from the plasma membrane/endosome pool back to the TGN was impaired, while recycling from endosomes to the plasma membrane was enhanced. In conclusion, our data indicate that the dileucine motif in the MPR46 tail is required for a sorting event in endosomes. PMID- 11208152 TI - Generation of MHC class I peptide antigens by protein processing in the secretory route by furin. AB - Cytosolic degradation of endogenously synthesized proteins by the proteasome and translocation of processed peptides to the endoplasmic reticulum by the transporters associated with antigen presentation constitutes the classical route for antigen presentation by MHC class I proteins. We have previously defined an alternative pathway in the secretory route involving proteolytic maturation of precursor proproteins for chimeric hepatitis B virus secretory core protein HBe containing a class I epitope at its carboxy-terminus. We extend those results by demonstrating that intracellular delivery of the trans-Golgi network protease furin increases both proteolytic maturation and antigen presentation of the chimeric HBe proteins. An additional class I epitope from the HIV envelope gp160 protein was inserted into this COOH-terminal region of two different chimeric HBe proteins. This epitope was also presented to CTL in a transporter-independent manner involving furin, and protein maturation and antigen presentation were also enhanced by furin over-expression. Presentation of this second epitope was restricted by a different class I allele, thus suggesting that antigen presentation by this new pathway may apply to any antigenic epitope and class I molecule. These results define the furin proteolytic maturation pathway of HBe in the secretory route as a general antigen processing route for MHC class I presentation. PMID- 11208153 TI - Biogenesis of insulin-responsive GLUT4 vesicles is independent of brefeldin A sensitive trafficking. AB - Insulin stimulates translocation of GLUT4 from an intracellular compartment to the plasma membrane in adipocytes. As a significant amount of GLUT4 is localised to the TGN, independently of the biosynthetic pathway, one possibility is that trafficking via the TGN is important in either intracellular sequestration or insulin-dependent movement to the cell surface. In this study we have used immuno electron microscopy to show that GLUT4 is localised to AP-1 vesicles in the TGN region in 3T3-L1 adipocytes. To dissect the role of this trafficking pathway we used brefeldin A (BFA) to disrupt AP-1 association with membranes. Despite a reorganisation of GLUT4 compartments following BFA treatment, the intracellular sequestration of GLUT4, and its insulin-dependent movement to the cell surface, was unaffected. BFA increased the half time of reversal of insulin-stimulated glucose transport from 17 to 30 min but did not prevent complete reversal. Furthermore, following reversal restimulation of glucose transport activity by insulin was not compromised. We conclude that under basal conditions GLUT4 cycles between the TGN and endosomes via the AP-1 pathway. However, neither this pathway, nor any other BFA-sensitive pathway, appears to play a major role in insulin-dependent recruitment of GLUT4 to the cell surface. PMID- 11208154 TI - The simian immunodeficiency virus envelope glycoprotein contains multiple signals that regulate its cell surface expression and endocytosis. AB - The cell surface expression of the envelope glycoproteins (Envs) of primate immunodeficiency viruses is, at least in part, regulated by endocytosis signal(s) located in the Env cytoplasmic domain. Here, we show that a membrane proximal signal that directs the simian immunodeficiency virus (SIV) Env to clathrin coated pits, and is conserved in all SIV and human immunodeficiency virus Envs, conforms to a YxxO motif (where x can be any amino acid and O represents a large hydrophobic residue). This motif is similar to that described for a number of cellular membrane proteins. By surface plasmon resonance we detected a high affinity interaction between peptides containing this membrane proximal signal and both AP1 and AP2 clathrin adaptor complexes. Mutation of the tyrosine in this membrane proximal motif in a SIV Env with a prematurely truncated cytoplasmic domain leads to a > or = 25-fold increase in Env expression on infected cells. By contrast, the same mutation in an Env with a full-length cytoplasmic domain increases cell surface expression only 4-fold. We show that this effect results from the presence of additional endocytosis signals in the full-length cytoplasmic domain. Chimeras containing CD4 ecto- and membrane spanning domains and a full-length SIV Env cytoplasmic domain showed rapid endocytosis even when the membrane proximal tyrosine-based signal was disrupted. Mapping experiments indicated that at least some of the additional endocytosis information is located between residues 743 and 812 of Env from the SIVmac239 molecular clone. Together, our findings indicate that the cytoplasmic domain of SIV Env contains multiple endocytosis and/or trafficking signals that modulate its surface expression on infected cells, and suggest an important role for this function in pathogenesis. PMID- 11208156 TI - The making and breaking of the endoplasmic reticulum. AB - The endoplasmic reticulum (ER) is a dynamic organelle central to many essential cellular functions. It is an important calcium store, which functions in cellular signal transduction cascades. It is also the site of entry for secreted proteins into the secretory pathway. Lumenal enzymes will fold and glycosylate these proteins, and if a protein is destined to be secreted, it will be packaged into membrane vesicles that bud off from the ER. The ER is also the site where most cellular lipids are synthesized. It is contiguous with the nuclear envelope, which serves as a diffusion barrier to control entry into and out of the nucleus. In the life cycle of a cell, the ER is in a constant flux of membrane traffic. What maintains the ER in the shape of an intact reticulum among this constant flux of material? We discuss the mechanisms that contribute to the biogenesis of the ER, the maintenance of the organelle, as well as processes that give the ER its characteristic shape and pattern of inheritance. PMID- 11208155 TI - ADPKD: a human disease altering Golgi function and basolateral exocytosis in renal epithelia. AB - Epithelial cells explanted from autosomal dominant polycystic kidney disease (ADPKD) tissue exhibit impaired exocytosis, specifically between the Golgi and basolateral membrane (Charron A, Nakamura B, Bacallo R, Wandinger-Ness A. Compromised cytoarchitecture and polarized trafficking in autosomal dominant polycystic kidney disease cells. J Cell Biol 2000; 148: 111-124.). Here the defect is shown to result in the accumulation of the basolateral transport marker vesicular stomatitis virus (VSV) G protein in the Golgi complex. Golgi complex morphology is consequently altered in the disease cells, evident in the noticeable fenestration and dilation of the cisternae. Further detailed microscopic evaluation of normal kidney and ADPKD cells revealed that ineffective basolateral exocytosis correlated with modulations in the localization of select post-Golgi transport effectors. The cytosolic coat proteins p200/myosin II and caveolin exhibited enhanced association with the cytoskeleton or the Golgi of the disease cells, respectively. Most cytoskeletal components with known roles in vesicle translocation or formation were normally arrayed with the exception of Golgi beta-spectrin, which was less prevalent on vesicles. The rab8 GTPase, important for basolateral vesicle targeting, was redistributed from the perinuclear Golgi region to disperse vesicles in ADPKD cells. At the basolateral membrane of ADPKD cells, there was a notable loss of the exocyst components sec6/sec8 and an unidentified syntaxin. It is postulated that dysregulated basolateral transport effector function precipitates the disruption of basolateral exocytosis and dilation of the ADPKD cell Golgi as basolateral cargo accumulates within the cisternae. PMID- 11208157 TI - Biogenesis of the sorting endosome: the role of Rab5. AB - Rab5 is a regulatory guanosine triphosphatase that is associated with the sorting endosome and participates in endosomal membrane fusion reactions. Recent experiments have provided insights into Rab5 function by demonstrating direct links between Rab5-interacting proteins and components of the membrane fusion apparatus. In addition, a realisation that Rab5 has additional functions in endosome biogenesis is emerging. These advances may be profoundly important in changing the way that we view the sorting endosome and in developing models that properly reflect the dynamic qualities of the endocytic pathway. PMID- 11208158 TI - Rab2 requires PKC iota/lambda to recruit beta-COP for vesicle formation. AB - The small GTPase Rab2 initiates the recruitment of soluble components necessary for protein sorting and recycling from pre-Golgi intermediates. Our previous studies showed that Rab2 required protein kinase C (PKC) or a PKC-like protein to recruit beta-COP to membrane (Tisdale EJ, Jackson M. Rab2 protein enhances coatomer recruitment to pre-Golgi intermediates. J Biol Chem 1998;273: 17269 17277). We investigated the role of PKC in Rab2 function by first determining the active isoform that associates with membranes used in our assay. Western blot analysis detected three isoforms: PKC alpha, gamma and iota/lambda. A quantitative binding assay was used to measure recruitment of these kinases when incubated with Rab2. Only PKC iota/lambda translocated to membrane in a dose dependent manner. Microsomes treated with anti-PKC iota/lambda lost the ability to bind beta-COP, suggesting that Rab2 requires PKC iota/lambda for beta-COP recruitment. The recruitment of beta-COP to membranes is not regulated by PKC iota/lambda kinase activity. However, PKC iota/lambda activity was necessary for Rab2-mediated vesicle budding. We found that the addition of either a kinase deficient PKC iota/lambda mutant or atypical PKC pseudosubstrate peptide to the binding assay drastically reduced vesicle formation. These data suggest that Rab2 causes translocation of PKC iota/lambda to vesicular tubular clusters (VTCs), which promotes the recruitment of COPI to generate retrograde-transport vesicles. PMID- 11208159 TI - The luminal domain of TGN38 interacts with integrin beta 1 and is involved in its trafficking. AB - TGN38 luminal domain (TGN38LD) was expressed in Cos-7 cells to identify potential binding partners. The luminal domain was secreted but, surprisingly, a significant portion bound to the plasma membrane. Cells overexpressing TGN38LD or the full-length molecule detached from the substratum and left footprints positive for TGN38. Unexpectedly, in these cells, TGN38 colocalizes with integrin alpha 5 beta 1 at the Golgi, the cell surface or in the footprints and an increased amount of both integrin subunits on the plasma membrane was observed. Under physiological conditions when TGN38 is not overexpressed, it interacts with integrin beta 1. This was demonstrated by reciprocal co-immunoprecipitation of integrin beta 1 and TGN38. Functional analysis reveals that modification of the trafficking of TGN38 results in a parallel change in the distribution of integrin alpha 5 beta 1, leading to the conclusion that TGN38 is involved in the trafficking of integrin beta 1. PMID- 11208160 TI - Procathepsin L self-association as a mechanism for selective secretion. AB - The lysosomal cysteine pro-protease procathepsin L was enriched in dense vesicles detectable when microsomes prepared from wild-type or transformed mouse fibroblasts were resolved on sucrose gradients. These dense vesicles did not comigrate with proteins characteristic of the endoplasmic reticulum, Golgi, endosomes or lysosomes. When gradient fraction vesicles were lysed at acidic pH in the presence of excess mannose 6-phosphate to prevent binding to mannose phosphate receptors, the majority of the procathepsin L was associated with the membrane, not the soluble, fraction. Immunogold labeling of procathepsin L in thin sections of cells or gradient fractions, using antibodies directed against the propeptide to avoid detection of the mature enzyme in dense lysosomes, revealed that the proenzyme was concentrated in dense cores localized in small vesicles near the plasma membrane and in multivesicular bodies. Consistent with the density of the gradient fraction and the electron density of the cores, yeast two-hybrid assays indicated the proenzyme could bind itself but could not interact with the aspartic proprotease procathepsin D. The data suggest that in mouse fibroblasts procathepsin L may self-associate into aggregates, initiating the formation of dense vesicles that could mediate the selective secretion of procathepsin L independent of mannose phosphate receptors. PMID- 11208161 TI - Gut thoughts on the Golgi complex. AB - The new millennium coincides within 1 year of Camillo Golgi's centennial celebrations. It is quite remarkable that the structure and formation of this organelle is as controversial today as was its mere existence from Golgi's time to the 1950s, when EM approaches were introduced. Since the late 1950s, two opposing models of Golgi structure and function have split the Golgi scientific community, namely vesicular transport versus organelle maturation. Although a few years ago Golgi maturation seemed to be 'out for the count', it has recently seen an almost messianic revival. In this review, I argue that this large-scale desertion from the vesicle transport model to the maturation camp is premature. I propose an alternative, dynamic steady-state model, in which transient tubular connections function in parallel to vesicular transport and that the biosynthetic pathway is made up of three major distinct compartments: the ER, the Golgi and the TGN. PMID- 11208163 TI - GLUT4--at the cross roads between membrane trafficking and signal transduction. AB - GLUT4 is a mammalian facilitative glucose transporter that is highly expressed in adipose tissue and striated muscle. In response to insulin, GLUT4 moves from intracellular storage areas to the plasma membrane, thus increasing cellular glucose uptake. While the verification of this 'translocation hypothesis' (Cushman SW, Wardzala LJ. J Biol Chem 1980;255: 4758-4762 and Suzuki K, Kono T. Proc Natl Acad Sci 1980;77: 2542-2545) has increased our understanding of insulin regulated glucose transport, a number of fundamental questions remain unanswered. Where is GLUT4 stored within the basal cell? How does GLUT4 move to the cell surface and what mechanism does insulin employ to accelerate this process? Ultimately we require a convergence of trafficking studies with research in signal transduction. However, despite more than 30 years of intensive research we have still not reached this point. The problem is complex, involving at least two separate signal transduction pathways which feed into what appears to be a very dynamic sorting process. Below we discuss some of these complexities and highlight new data that are bringing us closer to the resolution of these questions. PMID- 11208164 TI - Regulation of receptor tyrosine kinase signaling by endocytic trafficking. AB - Activated receptor tyrosine kinase (RTK) receptors are rapidly internalized and eventually delivered to the lysosomes. Although ligand-induced endocytosis was originally thought to be a mechanism of receptor inactivation, many studies suggest that receptors remain active within endosomes. This review discusses the role that internalized signaling complexes may play in different RTK systems including recent data on how ubiquitination may regulate this process. In general, it appears that some receptor systems have evolved to enhance endosomal signaling, as is the case for TrkA and NGF. In contrast, the insulin receptor system appears to limit the extent of endosomal signaling. The EGFR system is the intermediate example. In this case, some signals are specifically generated from the cell surface while others appear to be generated from within endosomes. This may act as a mechanism to produce ligand-specific signals. Thus, trafficking could play diverse roles in receptor signaling, depending on the specific cell and tissue type. PMID- 11208165 TI - In vitro assays of vesicular transport. AB - Movement of proteins and lipids between the various compartments of eukaryotic cells is fundamental to the maintenance of cellular homeostasis, and an understanding of the molecular mechanisms that govern these processes remains a key goal of cell biological research. This aim has been greatly facilitated by the development of assays that recapitulate specific events in vitro. In the following article we provide an overview of some of the currently used assays that measure the movement of proteins within the exocytic and endocytic pathways, and provide a starting point for those wishing to establish their own systems to study other vesicular transport steps. PMID- 11208166 TI - Reconstitution of clathrin-independent endocytosis at the apical domain of permeabilized MDCK II cells: requirement for a Rho-family GTPase. AB - This paper studies the endocytosis of ricin at the apical pole of polarized MDCK II cells after permeabilization of the cells basolaterally with streptolysin O. Ricin endocytosis after the addition of cytosol with an ATP-regenerating system was 2-3-fold higher than after the addition of a transport medium. A similar increase in ricin endocytosis was obtained by reconstitution of dialyzed cytosol with the nonhydrolyzable GTP analog, GTP gamma S, in the presence of an ATP regenerating system. The nonhydrolyzable GDP analog, GDP beta S, did not increase ricin uptake. In contrast to the data obtained with ricin, GTP gamma S was found to inhibit apical transferrin uptake in MDCK II cells transfected with the human transferrin receptor, and the data thus imply that GTP gamma S supports clathrin independent endocytosis. Electron microscopy (EM) demonstrated that free endocytic vesicles were formed from the apical pole of permeabilized MDCK II cells in the presence of GTP gamma S and that both a ricin-HRP conjugate, HRP, and cationized gold were endocytosed. Ricin endocytosis in the presence of intact cytosol, as well as GTP gamma S-stimulated ricin uptake, was inhibited by Clostridium botulinum C3 transferase, an enzyme found to inactivate Rho proteins. The data demonstrate that apical clathrin-independent endocytosis functions in the presence of GTP gamma S, and suggest that one or more of the small GTP binding proteins of the Rho family is involved in regulation of the apical clathrin-independent endocytosis in MDCK II cells. PMID- 11208167 TI - NBD-labeled phosphatidylcholine and phosphatidylethanolamine are internalized by transbilayer transport across the yeast plasma membrane. AB - The internalization and distribution of fluorescent analogs of phosphatidylcholine (M-C6-NBD-PC) and phosphatidylethanolamine (M-C6-NBD-PE) were studied in Saccharomyces cerevisiae. At normal growth temperatures, M-C6-NBD-PC was internalized predominantly to the vacuole and degraded. M-C6-NBD-PE was internalized to the nuclear envelope/ER and mitochondria, was not transported to the vacuole, and was not degraded. At 2 degrees C, both were internalized to the nuclear envelope/ER and mitochondria by an energy-dependent, N-ethylmaleimide sensitive process, and transport of M-C6-NBD-PC to and degradation in the vacuole was blocked. Internalization of neither phospholipid was reduced in the endocytosis-defective mutant, end4-1. However, following pre-incubation at 37 degrees C, internalization of both phospholipids was inhibited at 2 degrees C and 37 degrees C in sec mutants defective in vesicular traffic. The sec18/NSF mutation was unique among the sec mutations in further blocking M-C6-NBD-PC translocation to the vacuole suggesting a dependence on membrane fusion. Based on these and previous observations, we propose that M-C6-NBD-PC and M-C6-NBD-PE are transported across the plasma membrane to the cytosolic leaflet by a protein mediated, energy-dependent mechanism. From the cytosolic leaflet, both phospholipids are spontaneously distributed to the nuclear envelope/ER and mitochondria. Subsequently, M-C6-NBD-PC, but not M-C6-NBD-PE, is sorted by vesicular transport to the vacuole where it is degraded by lumenal hydrolases. PMID- 11208168 TI - Fission of biological membranes: interplay between dynamin and lipids. AB - Membrane budding and fission are the key stages of ubiquitous processes of formation of intracellular transport vesicles. We present a theoretical consideration of one of the most important types of fission machinery, which is mediated by GTPase dynamin and controlled by lipid composition of the membrane. We suggest a mechanism for collapse of a membrane neck driven by interplay between the dynamin collar and the bending elastic energy of the neck membrane. The collar plays a role of a rigid external skeleton, which imposes mechanical constraints on the neck. We show that in certain conditions the membrane of the neck loses its stability and collapses. Collapse can result from: (i) shifting of the spontaneous curvature of the neck membrane towards negative values, (ii) stretching of the dynamin collar, (iii) tightening of the dynamin collar. The three factors can act separately or concertedly. The suggested model accounts for the major experimental knowledge on membrane fission mediated by dynamin. It includes the elements of all previous models of dynamin action based on different sets of experimental results [Sever et al., Traffic 2000; 1: 385-392]. It reconciles, at least partially, the apparent contradictions between the existing alternative views on biomembrane fission machinery. PMID- 11208169 TI - Targeting of C-terminal (tail)-anchored proteins: understanding how cytoplasmic activities are anchored to intracellular membranes. AB - A class of integral membrane proteins, referred to as 'tail-anchored proteins', are inserted into phospholipid bilayers via a single segment of hydrophobic amino acids at the C-terminus, thereby displaying a large functional domain in the cytosol. This membrane attachment strategy allows eukaryotic cells to position a wide range of cytoplasmic activities close to the surface of an intracellular membrane. Tail-anchored proteins often, but not always, demonstrate a selective distribution to specific intracellular organelles. This membrane-specific distribution is required for the large number of targeting proteins that are tail anchored, but may or may not be critical for the numerous tail-anchored pro apoptotic and anti-apoptotic proteins of the Bcl-2 family. Recent work has begun to address the mechanism for targeting tail-anchored proteins to their resident membranes, but questions remain. What targeting signals determine each protein's intracellular location? Are there receptors for these signals and, if so, how do they function? What steps are required to integrate tail-anchored proteins into the phospholipid bilayers? In this Traffic interchange, we summarise what is known about tail-anchored proteins, and outline the areas that are currently under study. PMID- 11208170 TI - Gene therapy in wound healing--2000: a promising future. PMID- 11208171 TI - Gene therapy in wound repair and regeneration. AB - The potential use of gene therapy to treat human disease increases with the development of various physical, chemical, and biological methods to deliver genes to mammalian cells, and with our rapidly expanding knowledge of the human genome. One area of therapeutic interest for gene therapy is the treatment of wound healing disorders. Most recently, recombinant human growth factor therapy has been examined as a means to treat problem wounds. However, this approach suffers from the difficulty in providing an accurate dose of growth factor and the expense of the recombinant proteins. Delivery of a gene that could be expressed within the wound is an attractive alternative to application of the protein. This review discusses several methods that have been used to deliver genes encoding growth factor proteins into wounds and the advantages/disadvantages of each approach. Novel methods to regulate the expression of the transgene are also presented, highlighting the ability of these unique vector systems to adjust gene dose as the wound heals. We expect that gene therapy will become a significant treatment modality for those wound healing pathologies refractory to other wound management approaches in the years ahead. PMID- 11208172 TI - Particle-mediated gene therapy of wounds. AB - Gene therapy is becoming a reality, and it is a particularly attractive approach for wound healing, because the wound site is often exposed, the treatment and condition should be transient, and gene products such as growth factors and cytokines suffer from problems with bioavailability and stability. Among the techniques for gene delivery to the wound site, particle-mediated bombardment with a device called the gene gun has become an important developmental tool. This instrument has been used in numerous examples of wound gene therapy with growth factors or their receptors in the last decade. Among the advantages of particle-mediated bombardment are ease and speed of preparation of the delivery vehicle, the stability of the DNA preparation, the absence of (viral) antigens, the ability to target the projectiles to different tissue depths and areas, and the rapid shedding of both particles and DNA if they are targeted to the epidermis. Clinical application of the technology remains limited by the relatively low efficiency of the method, the potential tissue damage created by impact of the particles, and the coverage area. The gene gun can also be used to facilitate the discovery and validation of gene products as wound healing agents. PMID- 11208173 TI - Adenoviral-mediated gene transfer in wound healing. AB - The application of gene transfer strategies to wound healing is not an obvious use of this technology until one considers the important role of cytokines and growth factors in the normal wound healing response. Several gene transfer strategies have been proposed, from in vitro retroviral-mediated gene transfer with autologous transplantation, to in vivo plasmid based gene transfer as retroviral gene transfer. The limitations of these approaches have been efficiency of gene transfer, transgene expression and biologic response. Adenoviral-mediated gene transfer in wound healing is a relatively new application of this vector. The advantage of the adenovirus as a gene transfer vector lies in its ability to transduce nondividing cells of all types at very high efficiency without integration into the host cell's genome. The disadvantage of adenovirus as a vector is the relatively short duration of transgene expression and the inflammatory response it elicits. In the setting of wound healing brief duration of high levels of transgene may be all that is necessary to favorably influence wound healing. Secondly, as wound healing is fundamentally an inflammatory response, the inflammation elicited by the adenovirus may not be detrimental as long as the transgene is a growth factor with significant vulnerary effects such as platelet-derived growth factor-B. This review summarizes the current state of adenoviral-mediated gene transfer in experimental models of impaired wound healing which have laid the groundwork for proposed phase I clinical trials of adenoviral-mediated gene transfer of platelet-derived growth factor-B in chronic venous leg ulcers and chronic nonhealing diabetic foot ulcers. Adenoviral-mediated gene transfer is a useful tool in the study of the role of specific cytokines and growth factors in normal and impaired wound healing. Adenoviral-mediated gene transfer may hold significant promise for clinical application as a means of efficient growth factor delivery in correcting impaired wound healing. PMID- 11208174 TI - Matrix-enabled gene transfer for cutaneous wound repair. AB - Several growth factor proteins have been evaluated as therapeutic agents for the treatment of chronic dermal wounds. Unfortunately, most have failed to produce significant improvements in wound healing, in part due to ineffective delivery and poor retention in the wound defect. It has been proposed that gene therapy might overcome the limitations of protein therapy via ongoing transcription and translation, thus prolonging the availability of the therapeutic protein. Reasoning that it would be of further benefit to ensure retention of the DNA vector as well as the therapeutic protein within the wound defect, we have evaluated matrix-enabled gene transfer for cutaneous wound repair (Gene Activated Matrix). Formulations consisting of bovine type I collagen mixed with adenoviral or plasmid gene vectors have been evaluated in 3 in vivo models. The therapeutic transgenes employed encode human platelet-derived growth factor-A or -B, proteins key to each phase of normal wound repair. Increased granulation tissue formation, vascularization, and reepithelialization have been shown compared to controls treated with collagen alone or collagen containing a reporter gene vector. Further enhancements of the tissue repair response have been achieved by combining matrix-enabled gene transfer with molecular targeting, in which the DNA vector is conjugated to a growth factor ligand (basic fibroblast growth factor). These promising results support the clinical evaluation of gene activated matrices for the treatment of chronic dermal wounds. PMID- 11208175 TI - Clinical protocol: Phase I trial to evaluate the safety of H5.020CMV.PDGF-B for the treatment of a diabetic insensate foot ulcer. AB - Most patients with chronic wounds fail to heal in a reasonable period of time. Despite considerable advances in elucidating the molecular basis of wound repair, attempts at developing new therapies have been disappointing. In fact, in the few studies where cytokine growth factors have been efficacious, their effect has been dramatically less than would have been predicted from animal studies. We hypothesize that platelet-derived growth factor-BB, a growth factor associated with wound healing, when produced in large quantities within the wound bed due to adenovirus mediated gene overexpression by the cells of the wound bed will dramatically enhance wound healing. Simply stated, we plan to insure the delivery of the growth factor by using gene therapy techniques so that cells locally involved in the wound healing process will temporarily increase their production of platelet-derived growth factor-BB. We present the first step in the series of human investigations to test this hypothesis which is a phase I clinical trial. Our proposed study is designed to assess local and systemic toxicity, and the feasibility of using the maximum tolerated dose of H5.020CMV.PDGF-b associated with in vivo platelet-derived growth factor-BB gene transduction via an intraulcer injection of H5.020CMV.PDGF-b in patients with a diabetic insensate foot ulcer. PMID- 11208177 TI - Transplantation of virally transduced cells into the dermis of immunocompetent and immunodeficient (SCID) mice to determine gene expression profile and differential donor cell survival. AB - Cell therapy and bioengineering hold great promise as therapeutic approaches using cells and cell-derived factors to treat various pathologic or trauma induced states. One possible application is the transplantation of cells into wounded tissue to help regulate tissue repair. Cells engineered for optimal wound healing may help to minimize scarring following surgery or to enhance the rate of healing of chronic wounds. The purpose of the current study was to determine the effect of a viral insert, the LacZ-bearing, first generation adenovirus AdRGD, on the survival of dermally transplanted murine skin allogenic fibroblasts. The LacZ insert facilitated quantitation of both cell survival and gene expression and was used here to measure viable cell number. In addition to bearing the LacZ marker, the AdRGD vector is capable of carrying therapeutic gene inserts, so this study tested the feasibility of gene therapy for wound healing. Murine skeletal muscle PP6 (i.e., Pre-Plate 6) myogenic stem cells served as an alternate donor cell type. Cells were labeled with the LacZ-bearing AdRGD adenovirus vector and injected (50,000 cells/site) into the dorsal skin of adult normal, immunocompetent mice as well as in immunodeficient SCID mice. Skin biopsies were taken on days 0, 1, 2, 3, and 7 post-transplant, and assayed for LacZ expression. Soon after transplant (day 1), cell numbers underwent a transient decrease, but by day 2 post-transplant they were present in appreciable numbers. Between days 2 7 post-transplant, both allogenic fibroblasts and PP6 myogenic stem cells maintained survivability in similar numbers. Further, survival of transplanted cell types was similar in both normal, immunocompetent as well as SCID mice during this time period. There were no signs of acute inflammation or rejection in any of the samples. This study shows that AdRGD-transduced cells are not immunogenic in the mouse skin model and the cells show similar survival for the first 7 days post-transplantation independent of the cell type or immunocompetence of the host. PMID- 11208176 TI - Comparison and evaluation of gene therapy and epigenetic approaches for wound healing. AB - During the past decade considerable evidence has mounted concerning the importance of growth factors in the wound healing process both for cell replication and for stimulating reparative cells to synthesize and secrete extracellular matrix components. During normal wound healing the growth factor concentration has to be maintained at a certain level. If the growth factor concentration is too low, normal healing fails to occur. Whereas if the growth factor concentration is too high due to either over-expression of the growth factor or too much growth factor being applied to the wound, aberrant wound healing will occur. One approach for controlling the amount of growth factor at the wound site during normal healing is through gene therapy and the titration of gene dosage. However if a narrow window exists between the beneficial therapeutic effect and toxic effects with increasing gene dosage, an agent may be necessary to give in combination with gene therapy to regulate the over-expression of growth factor. In addition to genetic approaches to regulate wound healing, epigenetic approaches also exist. Antisense oligodeoxynucleotides have been shown to regulate wound repair in certain model systems and to determine the protein(s) necessary for normal wound healing. A novel approach to regulate the activity of collagen genes, thereby affecting fibrosis, is to use a sense oligodeoxynucleotide having the same sequence of the cis element which regulates the promoter activity of a particular collagen gene. This exogenous oligodeoxynucleotide will compete with the cis element in the collagen gene for the trans-acting factor which regulates promoter activity. These epigenetic approaches afford the opportunity to regulate over-expression of growth factor and therefore preclude the potential toxic effects of gene therapy. Both genetic and epigenetic approaches for regulating the wound healing process, either normal or aberrant wound healing, have certain advantages and disadvantages which are discussed in the present article. PMID- 11208178 TI - Use of the wound healing trajectory as an outcome determinant for acute wound healing. AB - Accurate and clinically practical methods for measuring the progress of acute wound healing is necessary before interventions designed to optimize and even accelerate acute wound healing can be applied. Complete wound closure rates and operative wound closure severity are irrelevant to most acute wounds since most are closed at the time of primary tissue repair and remain closed throughout healing. Analogous to chronic wound closure, the rate of increase of incision tensile strength progressively decreases as time passes and 100% unwounded tissue strength is never achieved making the endpoint definition of "healed" vague. Conceptualizing acute wound healing in terms of its design elements with reintegration into a final outcome lends itself to the description of acute wound healing as a mathematical trajectory. Frequently such an equation is a rate expressing the change in an acute healing parameter, most often tensile strength, over time. Such an approach also normalizes misinterpretations in analysis or errors in theory developed by measuring healing parameters at fixed points in time. Distributions of fractional strength gain times (e.g., 85% normal strength) can be determined using statistical methodology similar that used for failure time of survival analysis. Preclinical studies show that acute wound healing trajectories can be shifted to the left from a "normal" or "impaired" curve to an accelerated or more "ideal" curve. A useful method for measuring acute wound healing outcomes is therefore required before the basic science of acute wound healing is inevitably applied to the problem of acute surgical wounds. PMID- 11208179 TI - Thrombin peptide TP508 accelerates closure of dermal excisions in animal tissue with surgically induced ischemia. AB - TP508 is a synthetic peptide corresponding to amino acids 508 through 530 of human prothrombin. We previously demonstrated that a single topical application of TP508 stimulates revascularization and healing of acute incisional and excisional wounds in normal, healthy rat skin. To determine if TP508 would enhance wound healing in ischemic skin, we used bipedicle flaps, cranially based flaps, and free grafts to surgically create ischemic regions on the backs of rats. Full-thickness, circular excisions were made within the flaps or grafts and immediately treated with a single application of saline +/- TP508 (0.1 microg/wound). Compared to wound closure in normal skin, ischemic skin wounds exhibited delayed closure, and the length of delay correlated with the degree of surgically induced ischemia. TP508 significantly accelerated closure in both normal and ischemic skin, resulting in closure rates that were increased within the first 7 days of wounding by 30% in normal tissue and bipedicle flaps, 50% in cranially based flaps, and 225% in free grafts. Moreover, in both flap models, TP508 restored the rate of closure to a rate approximating the control rate observed in normal skin. Histological comparisons of wound tissue from normal skin and cranially based flaps showed that ischemia reduced early recruitment of inflammatory cells at day 1 but increased inflammatory cell numbers in wound beds at day 14. TP508 treatment of ischemic flap wounds significantly increased early inflammatory cell recruitment and restored the normal rapid resolution of the inflammatory phase. In addition, at day 7, TP508-treated wounds appeared to have an increased number of large functional blood vessels compared to saline controls. These studies support the potential efficacy of TP508 in treating ischemic wounds in humans. PMID- 11208180 TI - Lysophosphatidic acid enhances healing of acute cutaneous wounds in the mouse. AB - Lysophosphatidic acid is a phospholipid growth factor and intercellular signaling molecule released by activated platelets and injured fibroblasts that affects keratinocytes, fibroblasts, neutrophils,and monocytes. We therefore hypothesized that lysophosphatidic acid could influence the inflammation and reepithelialization phases of wound healing. Lysophosphatidic acid (100 microM) was applied daily for 5 days to 2 mm-diameter excisional mouse ear skin wounds and re-epithelialization was measured. We also evaluated whether the bioactivity of lysophosphatidic acid could be increased by zinc (Zn2+, 1 mM). Inflammatory cells were counted in wound sections after 1, 3, or 5 days of healing. Reepithelialization was accelerated significantly by either lysophosphatidic acid or lysophosphatidic acid + Zn2+ (p < 0.01 and p < 0.0001, respectively). Both lysophosphatidic acid solutions significantly increased the amount of new epithelium in the wounds on days 1, 2, and 3 (p < 0.05). Little wound area remained on day 4, and all wounds were fully reepithelialized by day 5. Lysophosphatidic acid did not affect the number of neutrophils or macrophages present in the wound area. Our findings show that lysophosphatidic acid increased the amount of reepithelialization in the early stages of cutaneous wound healing in excisional ear wounds, without affecting inflammatory function. PMID- 11208181 TI - Activation of latent transforming growth factor-beta1 is induced by mannose 6 phosphate/insulin-like growth factor-II receptor. AB - This study was conducted to further explore the mechanism of transforming growth factor beta1 (TGF-beta1) activation, which plays a critical role in many physiological and pathological conditions. We have previously shown that the large (270 kDa), but not small (40 kDa), mannose 6-phosphate receptors facilitate the cellular response to latent TGF-beta1 released from genetically modified cells. In this study, we explored the role of cell membrane associated transglutaminase and plasmin in mannose 6-phosphate receptor induced latent TGF beta activation using MS and MS-9 cells bearing either no receptors or the 270 kDa mannose 6-phosphate/insulin-like growth factor II receptors, respectively. As a source of latent TGF-beta1, PA317 cells were transfected with either pLin-TGF beta1 vector or pLin retroviral vector with no TGF-beta1 insert using calcium phosphate precipitation. The latency and bioactivity of TGF-beta1 in conditioned medium derived from transfected PA317 cells were evaluated by enzyme-linked immunosorbent assay and mink lung epithelial cell growth inhibition assay, respectively. The level of latent TGF-beta1 was 13-fold higher (20.1 +/- 0.4 vs. 1.5 +/- 0.03 ng/ml) in conditioned medium from pLin-TGF-beta1 transfected cells than that of control. The latency and bioactivity of TGF-beta1 released from pLin TGF-beta1 transfected cells were confirmed by evaluation of 3H-thymidine incorporation in Mv1Lu epithelial cells treated with non- and heat-activated 10% conditioned medium. The results showed a significantly lower 3H-thymidine incorporation in Mv1Lu epithelial cells treated with heat-activated PA317 conditioned medium (4% of control) relative to those treated with either control or nonheated conditioned medium. This inhibition was abrogated by addition of 40 microg/ml of TGF-beta1 neutralizing antibody. The level of 3H-thymidine incorporation was then evaluated in MS-9 cells receiving Dulbecco's modified Eagle medium containing either 0% 10%, 30% or 50% volumes of nonactivated PA317 conditioned medium for 24 hours. The results showed a markedly lower proliferation in response to 30% and 50% conditioned medium used in MS-9 cells. Under similar experimental conditions, addition of only mannose 6-phosphate, but not fructose 6-phosphate or mannose 1-phosphate, at 1 mM concentration restored the MS-9 cell proliferative response to latent TGF-beta1. The inhibitory effects of latent TGF-beta1 on MS-9 cell proliferation were restored by addition of either TGF-beta1 neutralizing antibody or cystamine, a transglutaminase inhibitor. In contrast, addition of aprotinin, a plasmin inhibitor, had a marginal influence on inhibitory effects of latent TGF-beta1 on MS-9 cell proliferation. Interestingly, a mixture of latent TGF-beta1 + MS-9 cell membranes, but not MS cell membranes, also inhibited the mink lung epithelial cell proliferation (34% of control). These findings indicate that mannose 6 phosphate/insulin-like growth factor II receptors are involved in latent TGF-beta activation and that is at least partly dependent on cell membrane associated transglutaminase, but not on plasmin. PMID- 11208182 TI - Inhibition of tumor necrosis factor-alpha attenuates wound breaking strength in rats. AB - Exogenous administration of tumor necrosis factor-alpha has been shown to both enhance and attenuate cutaneous healing in a dose-dependent manner. We examined the effects of tumor necrosis factor inhibition in the healing wound by both systemic and local administration of tumor necrosis factor-binding protein. Male Balb/C mice underwent dorsal skin incision with subcutaneous implantation of 20 mg polyvinyl alcohol sponges (4 per animal). In Experiment I, one group (n = 20) received intraperitoneal injections of tumor necrosis factor-binding protein (3 mg/kg) at the time of wounding, while another group (n = 20) received saline. Four animals from each group were euthanized on days 1, 3, 5, 7, and 14 postwounding. In Experiment II, one group (n = 10) received an intraperitoneal injection of tumor necrosis factor-binding protein (3 mg/kg) at the time of wounding and every third day thereafter. Another group (n = 10) received an intraperitoneal injection of saline at the time of wounding and every third day thereafter. In Experiment III, one group received a single intraperitoneal injection of tumor necrosis factor-binding protein (3 mg/kg) at the time of wounding (n = 7), or on postwounding day 4 (n = 7), or day 7 (n = 7). Another group received saline injections at the time of wounding (n = 7), or on postwounding days 4 or 7 (n = 7, respectively). All animals in Experiments II and III were killed at postwounding day 14. Wound breaking strengths were assessed using a tensiometer. Wound fluid collected from the implanted sponges was assayed for tumor necrosis factor-alpha and tumor necrosis factor-binding protein levels using a biological assay and enzyme-linked immunosorbent assay, respectively. Collagen gene expression in sponge granulomata was assessed by Northern analysis. Collagen deposition in sponges was quantified by measuring hydroxyproline content. Wounds were significantly weaker in the animals that received repeated injections of tumor necrosis factor-binding protein with a mean wound breaking strength of 93.1 g vs. 186.6 g in controls (p < 0.05). Wound breaking strength in groups that received a single injection of tumor necrosis factor-binding protein on either day 0, 4, or 7 postwounding were no different than their respective controls. There was no difference in the mean hydroxyproline content of sponges between any of the tumor necrosis factor-binding protein groups and their respective controls. Northern analysis for collagen I and III expression also revealed no differences. These data indicate that continued systemic administration of tumor necrosis factor-binding protein resulted in significantly weaker wounds with no corresponding differences in wound collagen content, and collagen gene expression. This suggests that tumor necrosis factor-alpha inhibition throughout healing leads to a qualitatively impaired wound without a quantitative alteration in collagen deposition. PMID- 11208183 TI - Cell, matrix changes and alpha-smooth muscle actin expression in repair of the canine meniscus. AB - Processes in the repair of a crevice in the knee joint meniscus were investigated in 10 dogs. Two 2-mm cylindrical plugs from each medial meniscus were removed, rendered acellular by freezing and thawing, and then reinserted into the meniscus. Dogs were euthanized at intervals of 3-52 weeks after surgery. The crevice between the plug and meniscus at 3 weeks after surgery was filled with a tissue containing alpha-smooth muscle actin-positive cells. One year after surgery, the plug had remodeled and was populated with spindle-shaped and fibrochondrocyte-like cells. The plug had an appearance intermediate between that of hyaline and fibrocartilage at this time, with a seamless integration in sites between the remodeled plug and the surrounding meniscus. alpha-smooth muscle actin-positive cells were concentrated at the interface of the remodeled plug and adjacent meniscus and at the surface of the plug. Therefore, remodeling of both the plug and meniscal tissue and the participation of alpha-smooth muscle actin positive cells appear essential for integration of the plug into the adjacent meniscal tissue. Cells in the superficial zone of the meniscus seem to be active in the repair process. A change in both the phenotype of the cells and the quality of the matrix toward a more hyaline state appears to be an integral part of the remodeling process in the meniscus. PMID- 11208185 TI - Editorial. PMID- 11208184 TI - Use of a noncontact radiant heat bandage and Staphylococcus aureus dermal infections in an ovine model. AB - Diabetic foot wounds are difficult to manage due to relative tissue ischemia and high rates of soft tissue infection. One potential treatment modality is the application of local radiant heat to promote wound healing and control infection. However, there are concerns that local heat will spread rather than control infection. We determined in this study the effect of a noncontact radiant heat bandage in controlling an ischemic soft tissue infection. Bilateral 10 x 15 cm dermal flaps were created in 15 adult range sheep. The flaps were inoculated intradermally with 107 Staphylococcus aureus in 3 separate areas. The control flap was left open to air, while the treatment flap was covered with a noncontact radiant heat bandage and heated to 38 degrees C for three 1-hour periods separated by two 1-hour nonheating periods daily. After 10 days, both dermal flaps were harvested and sent for quantitative bacteriology. Due to operative complications, 12 of 15 sheep completed the study. The heated flap temperature was significantly higher 39.2 +/- 0.5 degrees C (+/- SE) vs. the control flap 36.1 +/- 0.1 degrees C (p < 0.00001) and bacterial counts were significantly smaller in the heated flap (median 1.0 x 107 colony-forming units per gm tissue) when compared to the control flap (median 7.5 x 107) (p = 0.001). This study shows the use of a noncontact radiant heat bandage controls ischemic soft tissue infections in an ovine model. PMID- 11208186 TI - Both IgG and IgM anti-pig antibodies induce complement activation and cytotoxicity. AB - Hyperacute rejection of pig xenografts transplanted in humans is caused by endothelial cell binding of pre-formed xenoreactive antibodies (XAb) and activation of the classical pathway of complement. Human XAb mainly consist of anti-Galalpha1 3Gal antibodies, which occur in IgM, IgG and IgA classes. Whereas IgM anti-Galalpha1 3Gal antibodies have an established role in hyperacute rejection, the potential role of IgG XAb in this process is still controversial. The aim of the present study was to assess the specificity and functional properties of IgG and IgM XAb. Both classes were present in all human plasma samples tested, with a high inter-individual variability. Levels of IgG XAb did not correlate with levels of IgM XAb. Binding to Galalpha1 3Gal is strongly correlated with binding to the pig cell line PK15, both for IgG and for IgM, pointing to Galalpha1 3Gal as the major antigen recognized. Both purified IgM and IgG induced C3 deposition on PK15 cells and complement-dependent cytotoxicity in a dose-dependent way. The combination of IgG and IgM XAb resulted in an additive effect on cytotoxicity. Affinity-purified IgG anti-Galalpha1 3Gal antibodies were 22 times less potent than IgM in induction of cytotoxicity. These results indicate a quantitative, but not a qualitative, difference between IgM and IgG anti-pig antibodies concerning their complement-activating properties. Therefore, both classes of XAb are of importance in the pathogenesis of hyperacute rejection, and the relative importance of each class may differ considerably between individual patients, depending on the ratio of IgG and IgM XAb present in serum. PMID- 11208187 TI - Removal of bowel aerobic gram-negative bacteria is more effective than immunosuppression with cyclophosphamide and steroids to decrease natural alpha galactosyl IgG antibodies. AB - Natural alpha-Galactosyl (Gal) antibodies play an important role in the rejection of pig xenografts by humans and Old World monkeys. In this study we investigate the efficacy of two different strategies to reduce the serum level of natural anti-Gal antibodies. On the one hand, removal of aerobic gram-negative bacteria from the intestinal flora, because anti-Gal antibodies appear to be produced as a result of the continuous sensitization by these microorganisms. On the other hand, we studied the effect on these antibodies of an immunosuppressive regimen of cyclophosphamide and steroids. Ten baboons were treated for three months with norfloxacin (Nor Group; n=6) or cyclophosphamide and steroids (CyP Group; n=4). A further four baboons did not receive any treatment (Control Group). Aerobic gram negative bacteria became negative in stools of the Nor Group after two weeks of treatment, and remained undetectable until week 7. Thereafter, a gradual increase on the fecal concentration of aerobic gram-negative bacteria was observed despite the norfloxacin treatment. The mean anti-Gal IgG in the Nor Group gradually declined from week 4 to 9 to a mean of 62.7 +/- 18% of the baseline level, and during this period were significantly lower than in the CyP (P<0.02) and the Control (P<0.05) groups. No differences were observed between the three groups during the 16 weeks of follow-up in serum levels of anti-Gal IgM, hemolytic anti pig antibodies, total IgG, IgM and IgA. In conclusion, removal of normal aerobic gram-negative bacteria from the intestinal flora is more effective than immunosuppression with CyP and steroids in reducing the level of natural anti-Gal antibodies, although there is no discernible effect on IgM antibodies. PMID- 11208188 TI - Low molecular weight dextran sulfate prevents complement activation and delays hyperacute rejection in pig-to-human xenotransplantation models. AB - Dextran sulfate of 5000 molecular weight (DXS 5000) is known to block complement activation as well as the intrinsic coagulation cascade by potentiation of C inhibitor. The effect of DXS 5000 on hyperacute rejection (HAR) was tested in pig to-human xenotransplantation models. For in vitro testing, a cytotoxicity assay was used with the pig kidney cell line PK15 as target cells and fresh, undiluted human serum as antibody and complement source. Ex vivo pig lung perfusion was chosen to assess DXS 5000 in a physiologic model. Pig lungs were perfused with fresh, citrate-anticoagulated whole human blood to which 1 or 2 mg/ml DXS 5000 were added; the lungs were ventilated and the blood de-oxygenated. Pulmonary vascular resistance (PVR) and blood oxygenation (deltapO2) were monitored throughout the experiment. Autologous pig blood and human blood without DXS 5000 served as controls. In the PK 15 assay DXS 5000 led to a complete, dose-dependent inhibition of human serum cytotoxicity with an average IC50 of 43 +/- 18 microg/ml (n=8). Pig lungs perfused with untreated human blood (n=2) underwent HAR within 105 +/- 64 min, characterized by increased PVR, decrease of deltapO2, and generalized edema. Microscopically, capillary bleeding as well as deposition of human antibodies, complement and fibrin could be observed. Addition of DXS 5000 (n=4) prolonged lung survival to 170 +/- 14 min for 1 mg/ml and 250 +/- 42 min for 2 mg/ml. and PVR values as well as edema formation were comparable to control lungs that were perfused with autologous pig blood (n=2). Activation of complement (activation products in serum, deposition on lung tissue) and the coagulation system (fibrin monomers) were significantly diminished as compared to human blood without DXS 5000. Binding of anti-Gal antibodies was not influenced, and in vitro experiments showed no evidence of complement depletion by DXS 5000. In conclusion, DXS 5000 is an efficient complement inhibitor in pig-to-human xenotransplantation models and therefore a candidate for complement inhibitory/anti-inflammatory therapy either alone or in combination with other substances and warrants further investigation. PMID- 11208189 TI - Human membrane cofactor protein (MCP, CD 46) protects transgenic pig hearts from hyperacute rejection in primates. AB - Recently, we and others have shown the prolongation of xenograft survival with the use of transgenic pigs bearing human CD 59 and DAF complement regulatory proteins (CRP). We now report heart transplantation using a new line of transgenic pigs bearing a different human CRP, membrane cofactor protein (MCP, CD 46). We transplanted three MCP transgenic and three wild-type porcine hearts into baboons suppressed with cyclosporine, methylprednisone, and rapamycin or cyclophosphamide. In addition, recipients were treated with extracorporeal plasma perfusion to remove alpha-Gal reactivity. The wild-type grafts were rapidly rejected at 60 to 80 min. Two functioning MCP hearts were removed after 5 and 46 h for histological examination. One MCP heart showed vigorous function until postoperative day 16. Immunohistochemistry of both wild-type and MCP-transgenic hearts showed strong deposition of IgM. In contrast, there was less MAC deposition in the transgenic graft as compared to the wild-type control. MCP is another CRP capable of decreasing the features of hyperacute rejection of cardiac xenografts in baboon recipients. PMID- 11208190 TI - Preconditioning with the prostacyclin analog epoprostenol and cobra venom factor prevents reperfusion injury and hyperacute rejection in discordant liver xenotransplantation. AB - Liver xenografts transplanted from guinea pig to rat suffer from inadequate organ reperfusion and initial dysfunction, despite sufficient complement depletion using cobra venom factor (CVF). Reperfusion injury is prevented when complement depleted donors are treated with the prostacyclin analog epoprostenol. Histological analysis suggests that epoprostenol preconditioning prevents post reperfusion spasms of the intrahepatic branches of the portal vein and strongly reduces appearance of hepatocyte apoptosis shortly after transplantation. Cobra venom-treated rats show breakdown of glucose metabolism and die in acute hypoglycaemia, whereas the additional application of epoprostenol restores gluconeogenesis. Consequently, recipient survival after epoprostenol and CVF treatment is significantly improved compared with animals receiving CVF only (5.1 +/- 2.6 h vs. 17.9 +/- 5.1 h). These data demonstrate that initial dysfunction of discordant liver grafts in the guinea-pig-to-rat species combination, can be overcome by the application of epoprostenol combined with CVF. Using this pharmacologic regimen, the discordant guinea-pig-to-rat model appears useful to study further questions concerning functional and immunological compatibility of a discordant liver xenograft. PMID- 11208191 TI - Immortalized bone-marrow derived pig endothelial cells. AB - Primary cultures of porcine endothelial cells (EC) can only be maintained for a limited number of passages. To facilitate studies of xenogeneic human anti-pig immune responses in vitro, pig microvascular bone-marrow (BM) and macrovascular aortic EC were obtained from our herd of partially inbred miniature swine, homozygous for the major histocompatibility locus, and immortalized with a modified SV40 large T vector. The resulting BM-derived (2A2) and aortic (PEDSV.15) immortalized EC lines showed unlimited growth and EC phenotype as indicated by expression of von Willebrand Factor (vWF) and low density lipoprotein (LDL) receptors as well as by formation of typical cobblestone monolayers. Ultrastructural studies revealed morphological similarities in primary and immortalized EC. Flow cytometry analysis demonstrated constitutive SLA class I expression by all lines whereas SLA class II was only expressed after stimulation with porcine IFNgamma. Furthermore, pig CD34 mRNA was detected by Northern blot analysis in primary and immortalized aortic EC but not in 2A2. Both EC lines expressed a number of myeloid markers, adhesion molecules and xenoantigens, the latter being determined by binding of human natural antibodies. Gene transfer into the porcine EC lines was successfully performed by electroporation or calcium-phosphate transfection, as well as by adenoviral infection. Finally, the functional similarity between primary and immortalized EC was demonstrated in adhesion and cytotoxicity assays. Together, these results suggest that 2A2 and PEDSV. 15 represent valuable tools to study both human cellular and humoral immune responses in vitro against pig EC derived from microvascular and large vessels. PMID- 11208192 TI - Characterization of human killer cell reactivity against porcine target cells: differential modulation by cytokines. AB - The cytotoxic cell response to porcine cells by human lymphocytes, and the modulation of cytolytic cellular activity by human cytokines were investigated. Human peripheral blood mononuclear cells (PBMC) and purified lymphocyte subsets were co-cultured with fresh irradiated porcine stimulator cells and examined for the development of lytic activity and for their proliferative response. Porcine target cells included a new cell line, MS-PBMC-J2 (designated J2; SLA-DR+MHC class I+CD2+CD3 CD8+CDI6+CD45+), aortic and microvascular endothelial cells. Initial results showed that natural killer (NK) cells were fivefold more efficient in killing porcine target cells compared with T cells. IL-12 augmented the killing of porcine target cells by human NK cells beyond that induced by stimulation with cells alone. In contrast, IL-2 and IL-15 often induced substantial human NK cell mediated killing of porcine target cells, including endothelial cells in the case of IL-2 where such targets were examined, even in the absence of stimulator cells. Finally, neither IL-18 nor IL-8 had any effect beyond background on NK cell mediated killing of porcine target cells. These findings show that cytokines that would be produced in a xenograft setting clearly modulate the ability of human cytolytic cells to kill porcine targets. In addition, fresh unstimulated human NK cells lysed J2 and porcine aortic endothelial cells, but not porcine microvascular endothelial cells, suggesting the possibility of rapid attack of xenografts by NK cells, and differential susceptibility of endothelial cells from different vascular structures to this attack. PMID- 11208193 TI - Oral delivery of xeno-antigen combined with non-depleting anti-CD4 monoclonal antibody induces significantly prolonged survival of concordant skin xenograft. AB - Oral administration can induce unresponsiveness to protein antigens. Therefore, we examined whether oral administration of xeno-antigen could induce the prolonged survival of xenogeneic skin grafts. CBA mice were given 1 x 10(7) SD rat splenocytes orally, 7 days before transplantation of a SD rat skin in the presence or absence of a non-depleting anti-CD4 monoclonal antibody (mAb) (YTS177, 200 microg/dose, 8 and 7 days relative to transplantation). All skin grafts survived with a median survival time (MST) of 62 days when xeno-antigens were administered orally in combination with anti-CD4 mAb. Mice treated with anti CD4 mAb alone or oral administration of xeno-antigen alone induced modest prolonged survival of rat skin grafts (MST = 18 and 19 days, respectively) while naive mice rejected rat skin acutely (MST= 12 days). Oral administration alone or combined with anti-CD4 mAb reduced the level of xeno-antibody production compared with that in untreated mice after transplantation. Xenogeneic mixed leukocyte response was reduced when splenocytes from mice pre-treated with oral administration of xenogeneic cells were used as the responder compared with that in untreated mice. Oral delivery of xeno-antigen plus non-depleting anti-CD4 mAb can induce prolongation of concordant xenogeneic skin grafts. PMID- 11208194 TI - "Literature update 1999, part 3". PMID- 11208195 TI - A tribute to leadership, dedication, and performance in publishing. PMID- 11208196 TI - Periapical abscess formation and resolution adjacent to dental implants: a clinical report. AB - The vitality of teeth adjacent to dental implants should be considered in the treatment planning of dental implants. Both the restorability of an endodontically treated tooth and the risk of infection of the adjacent implant are important factors in planning for success. Given the illustrated difficulties and difficulties associated with resolving periapical infections of teeth and implants, it is essential to define the vitality of teeth by careful pulp testing and to consider the integrity of existing questionable, endodontically treated teeth before implant treatment. The risk of periapical infection at teeth adjacent to implants must be minimized. PMID- 11208197 TI - Fabrication of a digitally scanned, custom-shaped abutment: a clinical report. AB - A procedure for the creation of a custom, anatomic implant abutment copy milled with digitally scanned information has been described. The definitive restoration was a custom-machined abutment with a ceramic crown that had an aluminous oxide core. PMID- 11208198 TI - An endosseous, implant-retained obturator for the rehabilitation of a recurrent central giant cell granuloma: a clinical report. AB - The prosthodontic rehabilitation of a patient with a recurrent maxillary CGCG has been described. The patient's immense defect originally was rehabilitated with a scapular microvascular free flap, endosseous dental implants, and an ISP that became obsolete by virtue of the resection of recurrent disease and the subsequent need for velopharyngeal obturation. The patient was provided with a surgical obturator at the time of the resection of the recurrent CGCG. The surgical obturator thereafter was modified into an interim obturator to provide velopharyngeal competence while the soft tissues around the palatal defect healed. Finally, the construction of a bar-retained definitive obturator markedly improved the patient's speech, mastication, and deglutition. PMID- 11208199 TI - Teaching an abbreviated impression technique for complete dentures in an undergraduate dental curriculum. AB - STATEMENT OF PROBLEM: Traditional methods for teaching complete denture fabrication are time-consuming, difficult to master, and not used by many general practitioners. PURPOSE: This study compared the efficacy of traditional denture fabrication techniques with a more abbreviated method in a dental school setting. MATERIAL AND METHODS: A retrospective record review of 80 completely edentulous patients treated by predoctoral dental students was completed. Forty patients were treated with traditional denture techniques; the other 40 patients were treated with an abbreviated method. The data abstracted included the number of visits to completion and the number of postinsertion visits and relines required within the first 3 months after delivery. A Wilcoxon rank sum test was performed to determine statistical significance between the groups with regard to number of visits for fabrication and postinsertion adjustments. A test for a difference in proportions by using the normal approximation to the binomial distribution was performed for statistical analysis of the incidence of relines. RESULTS: The abbreviated denture technique resulted in a statistically significant difference in the number of visits for fabrication (P<.01) and postinsertion adjustments (P<.05.) There was no difference (P=.39) in the number of relines between the 2 groups. CONCLUSION: Teaching the abbreviated complete denture technique in an undergraduate dental clinic decreased the number of appointments necessary to complete denture therapy without increasing the number of adjustments or reline procedures. PMID- 11208200 TI - The pontic-splinted procedure for tooth and denture base additions in denture repair. AB - Various methods for adding teeth to existing dentures have been used clinically. Although a direct, single-tooth addition method saves time, it often is difficult to achieve an esthetic appearance when adding several missing anterior teeth with this technique. Indirectly adding teeth may achieve a better esthetic result, but this method is time-consuming. This article describes the pontic-splinted procedure, an indirect method for replacing several anterior teeth and part of the denture base that can save time and, at the same time, help the clinician achieve acceptable esthetics. PMID- 11208201 TI - Comparative in vitro evaluation of two provisional restorative materials. AB - STATEMENT OF PROBLEM: Provisional crowns traditionally have been associated with problems such as poor occlusion, contour, fit, and finish. Fabrication procedures should be uncomplicated and predictable within a realistic time frame. PURPOSE: The purpose of this study was to compare the quality of provisional restorations fabricated by dental students from 2 different materials (bis-acryl composite resin and PMMA) and identify the advantages and disadvantages associated with each material. MATERIAL AND METHODS: This study evaluated the occlusion, contour, marginal adaptation, and finish of 222 provisional crowns fabricated by 2 groups (A and B) of dental students. One bis-acryl composite resin material (Integrity) and 2 PMMA resins (C&B Resin and Snap) were evaluated. RESULTS: For group A, Integrity was statistically superior (P<.05) to C&B Resin in all 4 categories for anterior provisional crowns. For posterior provisional crowns, Integrity proved superior in the categories of contour and marginal adaptation, but no significant differences were established for occlusion and finish. For group B, Integrity was statistically superior to Snap in the categories of occlusion, contour, and marginal adaptation, whereas there was no statistical difference in finish. When all 4 categories were analyzed, Integrity was found to be statistically superior. CONCLUSION: Bis-acryl composite resin (Integrity) was significantly superior to PMMA (C&B Resin and Snap) as a provisional restorative material. PMID- 11208202 TI - Evaluation of high-temperature distortion of high-palladium metal-ceramic crowns. AB - STATEMENT OF PROBLEM: Crown fit is a prerequisite for long-term clinical success; however, crown distortion may occur during porcelain firing. The dimensional stability of some high-palladium alloys at high temperatures has been questioned. PURPOSE: The purpose of this study was to use a new method to measure the distortion of copings for metal-ceramic single units of selected high-palladium alloys with compositions representative of commercial alloys. MATERIAL AND METHODS: Four high-palladium alloys containing copper and 3 containing no copper were tested. A palladium-silver alloy was included for comparison, and a gold palladium alloy served as the control. By using reference points scribed on the margin, the mesiodistal and buccolingual margin diameters of identical copings were measured with a traveling microscope at 4 stages: as-cast, oxidized, after 2 simulated opaque porcelain firings, and after 2 simulated dentin porcelain firings. The margin distortions for the various specimen groups representing combinations of alloys, stages, and measurement diameters were compared with the use of 1-way analysis of variance and a multiple range test. RESULTS: Most of the high-palladium alloys had high-temperature distortions that were not significantly different from those of the control alloy. The distortions occurred principally during the oxidation cycle. The effect of mesiodistal groove reinforcement on preventing distortion was not the same for all alloys. CONCLUSION: The results suggest that small observed distortions of these alloys will not produce clinical problems. Several laboratory techniques are available to counteract the distortions. PMID- 11208203 TI - A patient-based assessment of implant-stabilized and conventional complete dentures. AB - STATEMENT OF PROBLEM: Outcomes of oral implant therapy have been described primarily in terms of implant survival rates and the durability of implant superstructures. Reports of patient-based outcomes of implant therapy have been sparse, and none of these studies have used oral-specific health status measures. PURPOSE: This study assessed the impact of implant-stabilized prostheses on the health status of complete denture wearers using patient-based, oral-specific health status measures. It also assessed the influence of preoperative expectations on outcome. MATERIAL AND METHODS: Three experimental groups requesting replacement of their conventional complete dentures completed an Oral Health Impact Profile (OHIP) and a validated denture satisfaction scale before treatment. One group received an implant-stabilized prosthesis (IG), and 2 groups received new conventional complete dentures (CDG1 and CDG2). After treatment, all subjects completed the health status measures again; preoperative data were compared with postoperative data. RESULTS: Before treatment, satisfaction with complete dentures was low in all 3 groups. Subjects requesting implants (IG and CDG1) had high expectations for implant-stabilized prostheses. Improvement in denture satisfaction and OHIP scores was reported by all 3 groups after treatment. Subjects who received their preferred treatment (IG and CDG2 subjects) reported a much greater improvement than CDG1 subjects. Preoperative expectation levels did not appear to influence satisfaction with the outcomes of implant therapy in IG subjects. CONCLUSION: Subjects who received implants (IG) that replaced conventional complete dentures reported significant improvement after treatment, as did subjects who requested conventional replacement dentures (CDG2). The OHIP appears useful in identifying patients likely to benefit from implant-stabilized prostheses. PMID- 11208204 TI - Freestanding and multiunit immediate loading of the expandable implant: an up-to 40-month prospective survival study. AB - STATEMENT OF PROBLEM: The subject of immediate loading of dental implants has received substantial attention, although it appears to conflict with the basic principles of dental implant therapies developed and established over the past 20 years. Clinicians would welcome the use of a reliable, immediate-loading implant system. PURPOSE: The purpose of this study was to evaluate the effectiveness of an expandable implant design for immediate and delayed loading and for freestanding and multiunit situations. MATERIAL AND METHODS: Two hundred eighty six immediate-load Sargon implants were placed in 75 patients during a 40-month period. Of the 273 implants that survived, 81 were placed into fresh extraction sockets and immediately loaded, 162 were placed into healed sites and immediately loaded, and 30 were delay loaded. Some implants that had failed to remain stable after immediate loading became stable and osseointegrated after the load was removed and their expansion mechanisms were reactivated. RESULTS: The overall survival rate during the 40-month period was 96.0% in the maxilla and 94.8% in the mandible. Implants placed in fresh extraction sockets showed a 98.9% survival rate. Healed sites showed a 93.9% survival rate. Immediate loading of 52 fresh extraction socket implants in the maxilla showed a 100% survival rate during the evaluation period. CONCLUSION: Within the limitations of this study, it was shown that the feature of mechanical expandability may provide operators some control over implant stability during the vulnerable period after immediate loading of single, freestanding implants. PMID- 11208205 TI - Three-dimensional quantification of color-marked occlusal paths on anatomically oriented casts. AB - STATEMENT OF PROBLEM: The analysis of occlusal contacts on mounted diagnostic casts is an important task in prosthetic diagnostics. However, it is still restricted mainly to qualitative aspects because existing measuring techniques fail to provide 3-dimensional data for more than a few single points in acceptable time. PURPOSE: The aim of this study was to develop a method for quantifying occlusal contacts and paths by using anatomically oriented diagnostic casts and to design the method to allow fast acquisition of digital 3-dimensional coordinates. MATERIAL AND METHODS: Plaster casts with color-marked contacts were digitized optically with a profilometric system based on the fringe projection technique. Digital camera images taken simultaneously were used to define the contact areas by marking them either manually or automatically with the help of image-processing routines. Three-dimensional coordinates were determined by finding the corresponding points within the profilometric data set. RESULTS: Color-marked contact areas on diagnostic casts were successfully digitized with a computer-controlled, automatic setup in approximately 30 seconds. The accuracy of the acquired 3-dimensional data was estimated to be better than 60 microm in lateral and 30 microm in height resolution. The data set was visualized and evaluated in a skull related coordinate system. SUMMARY: This study verified the use of a new tool to quantify color-marked occlusal contacts on diagnostic casts in terms of spatial coordinates. The resulting digital data may be stored easily and analyzed numerically as well as visualized 3-dimensionally with computer graphic equipment. Because the anatomic orientation of the casts is maintained throughout the measurement process, it is possible to compare the data with electronically registered condyle paths and therefore to investigate, for example, their relation to the corresponding guidance paths of the frontal teeth and the canines in dynamic occlusion. PMID- 11208206 TI - A review of saliva: normal composition, flow, and function. AB - An adequate supply of saliva is critical to the preservation and maintenance of oral tissue. Clinicians often do not value the many benefits of saliva until quantities are decreased. Much is written on the subject of salivary hypofunction, but little attention is paid to normal salivary flow and function. This article is a brief, up-to-date overview of the literature on the basics of normal salivary composition, flow, and function. A review of the literature was conducted using MEDLINE and Healthstar (1944 through 1999); articles were selected for inclusion on the basis of relevance and significance to the clinician. PMID- 11208207 TI - Setting characteristics of five autopolymerizing resins measured by an oscillating rheometer. AB - STATEMENT OF PROBLEM: Ease of handling and the working time of autopolymerizing resins are directly associated with the setting characteristics during polymerization. PURPOSE: This study assessed the setting characteristics of autopolymerizing resins by measuring viscosity changes and tested the hypotheses that: (1) different products have different viscosity increase patterns during polymerization, and (2) the increased rate of viscosity is not proportional to the length of the setting time. MATERIAL AND METHODS: Viscosity change during polymerization was measured in 5 test materials (Unifast II, ADFA, META FAST, Miky, and Trim) with an oscillating rheometer. The working time was defined as the time required for a 5% reduction in the amplitude of the rheometer trace. The setting time was measured as the time required to reach zero amplitude on the rheometer trace. RESULTS: The order of working times from longest to shortest was Trim, Unifast II and META FAST, ADFA, Miky (ANOVA, P<.0001). The order of setting times from longest to shortest was Trim, META FAST, Miky, ADFA, Unifast II. Materials that had rapid setting times did not necessarily have short working times. Unifast II showed well-balanced setting properties that satisfied both longer working time and faster setting time. CONCLUSION: Autopolymerizing resins have setting characteristics specific to the brand. Knowledge of these characteristics is essential for selection of the appropriate resin product depending on the purpose of clinical usage and the individual dentist's technique. PMID- 11208208 TI - Effects of flowable composite lining and operator experience on microleakage and internal voids in class II composite restorations. AB - STATEMENT OF PROBLEM: When inexperienced clinicians perform class II composite restorations, improper placement techniques can lead to problems, including marginal adaptation and void formation. PURPOSE: The aim of this study was to determine the influence of flowable composite linings on marginal microleakage and internal voids in class II composite restorations performed by practitioners with different levels of experience. MATERIAL AND METHODS: Eighty extracted molars were prepared with mesial and distal class II cavity preparations and divided into 4 groups. Each group was restored separately with the following materials: Prodigy/Revolution lining (group I), Prodigy (group II), Tetric Ceram/Tetric Flow lining (group III), and Tetric Ceram (group IV). Each group was equally divided and restored by 2 practitioners, one experienced and another untrained in composite restorations. After restoration, all teeth were stored for 24 hours, thermocycled (at 5 degrees C to 60 degrees C) 1500 times, and soaked in 2% basic Fuchsin dye for 24 hours. After soaking, the teeth were sectioned, and gingival marginal microleakage and internal voids (at the gingival wall interface and in the cervical and the occlusal parts) were recorded. Data were analyzed with the Kruskal-Wallis test. RESULTS: There was no significant reduction in microleakage for either practitioner. There were fewer interface voids within pairs with or without flowable composite linings made by the experienced practitioner (P<.05). CONCLUSION: When flowable composite lining was placed at the gingival floor of a class II composite restoration by an experienced practitioner, voids in the restored interface were reduced. Gingival marginal sealing was not improved by the same technique. PMID- 11208209 TI - Effects of two silane coupling agents, a bonding agent, and thermal cycling on the bond strength of a CAD/CAM composite material cemented with two resin luting agents. AB - STATEMENT OF PROBLEM: Surface treatment of CAD/CAM-generated composite material is important for a strong bond of resin luting agents to composite material. Purpose. This study evaluated the shear bond strengths of 2 dual-cured resin luting agents to a CAD/CAM composite material and the effect of silane coupling agent and bonding resin on the bond strength. MATERIAL AND METHODS: Rectangular- and disk-shaped CAD/CAM composite materials were untreated or treated with 1 of the 2 silane coupling agents or bonding resin and then cemented together with 1 of the 2 dual-cured resin luting agents. Half of the specimens were stored in water at 37 degrees C for 24 hours, the other half thermocycled 50,000 times before shear bond strength testing. Shear bond strengths were measured with a servohydraulic mechanical testing machine, and results were analyzed with 2-way analysis of variance. RESULTS: Surface treatment by silane coupling agent improved the shear bond strength when compared with nontreatment. Specimens treated with bonding resin showed significantly greater shear bond strength than the untreated groups. However, all specimens had the same adhesive failures at the composite-luting agent interface as untreated groups. When the CAD/CAM composite material was treated with 1 of the 2 silane coupling agents, no significant differences in bond strength were noted between water storage alone and after 50,000 thermocycles. For the 2 groups treated with bonding resin or silane coupling agent and cemented with 1 of the 2 dual-cured resin luting agents, there were significant increases in bond strength after 50,000 thermocycles, compared with specimens that were not subjected to thermal cycling. On the other hand, for the 2 untreated groups, there were significant decreases in bond strength after thermocycling. After 50,000 thermocycles, all specimens treated with silane coupling agent and then cemented with 1 of the 2 resin luting agents showed cohesive failures within the composite material. CONCLUSION: The application of a silane coupling agent to the CAD/CAM composite surface provided the highest bond strength between the resin luting agent and composite after long term thermal cycling. PMID- 11208210 TI - Pilot study of the relationship between the hardness and abrasion resistance of two base metal alloys used for metal-ceramic restorations. AB - STATEMENT OF PROBLEM: Base metal alloys present high values of strength and hardness, which have been associated with the greater abrasion resistance and polishing of metal-ceramic restorations. However, surface hardness has been shown to be a poor indicator of abrasion resistance. PURPOSE: The study aimed to compare the hardness and abrasion resistance of Ni-Cr alloys and determine whether there is a correlation between these 2 properties. MATERIAL AND METHODS: Two Ni-Cr alloys for metal-ceramic restorations with different hardness values were subjected to the following procedures: (1) initial measurement of Vickers hardness, (2) a series of abrasion cycles, (3) measurement of mass loss after each cycle, and (4) Vickers hardness measurements after each cycle. RESULTS: For each alloy, linear regression revealed a negative correlation between hardness and reduction in mass. The higher hardness of alloy A was associated with higher mass loss during abrasion when compared with alloy B. CONCLUSION: There was no significant correlation between hardness and mass loss for either alloy. PMID- 11208212 TI - Methods for recycling discarded mouth guard sheets. PMID- 11208211 TI - Electrochemical corrosion of titanium and titanium-based alloys. AB - STATEMENT OF PROBLEM: Two varieties of unalloyed titanium, Ti-6Al-4V and NiTi, commonly are used in medical and dental fields. Several other types of alloys for potential use in these fields have been developed, including Ti-4.5Al-3V-2Mo-2Fe and vanadium-free alloys (Ti-5Al-2.5Fe and Ti-5Al-3Mo-4Zr). The corrosion of these alloys under simulated physiologic conditions is not known. Purpose. This study compared the corrosion behaviors of 6 titanium materials through electrochemical polarization tests in 37 degrees C Ringer's solution. MATERIAL AND METHODS: The applied voltage was potentiostatically scanned from -0.6 to 1.0 V. From polarization curves, the corrosion rate (averaged over 3 samples) for each alloy was calculated and compared with that of other alloys. Analysis of variance (ANOVA) and the Student-Newman-Keuls multiple range test were performed at a 95% overall confidence level to identify statistically significance differences in corrosion rates. Surface oxide films were identified by electron diffraction, and the electrolyte medium was analyzed by atomic absorption spectrophotometry after each alloy was tested. RESULTS: Commercially pure titanium and Ti-5Al-2.5Fe were the most resistant to corrosion; Ti-5Al-3Mo-4Zr, Ti-6Al-4V, and NiTi were the least resistant to corrosion. NiTi exhibited pitting corrosion along with transpassivation. CONCLUSION: Electron diffraction patterns indicated that all titanium alloys were covered mainly with rutile-type oxide (TiO(2)) after corrosion tests. The oxides that formed on Ti-5Al-2.5Fe were identified as a mixture of TiO(2) and Ti(9)O(17), and those that formed on NiTi were identified as a mixture of TiO(2) and Ni(2)Ti(4)O. PMID- 11208213 TI - How to achieve a path of insertion for a provisional fixed partial denture retained by stainless steel posts. PMID- 11208214 TI - Implant superstructure hygienic modification. PMID- 11208215 TI - Organized method for ultrasonically cleaning and sterilizing small prosthetic components used in implant therapy. PMID- 11208216 TI - Re: Fabrication of a two-piece superstructure for a fixed detachable implant supported mandibular complete denture. Golden et al. J Prosthet Dent 2000;84:205 9. PMID- 11208218 TI - Effect of direction of applied mobilization force on the posteroanterior response in the lumbar spine. AB - OBJECTIVE: The purpose of this study was to investigate whether changing the direction of applied force affects measured posteroanterior stiffness and associated pelvic (sacral) and lower thoracic rotations. DESIGN: A repeated measures design was used. SETTING: University biomechanical laboratory. PARTICIPANTS: Twenty-four subjects (14 male, 10 female) with no history of recent low back pain or contraindications to mobilization volunteered for testing. MAIN OUTCOME MEASURE: Posteroanterior stiffness was assessed at vertebral levels L3 and L5 through use of 3 sagittal plane directions of applied force; the directions differed by 10 degrees. The amount of sacral and lower thoracic rotation that occurred during loading between 30 and 100 N was also recorded. RESULTS: A small but significant variation of stiffness with direction of applied force was found. At L3, mean stiffness was greatest when the posteroanterior force was applied in a base direction; it was 11% less when the force was applied 10 degrees more caudad than the base direction and 14% less when the force was applied 10 degrees more cephalad than the base direction. There was no significant effect of direction when the force was applied at L5. Both sacral and thoracic rotations displayed significant variation with direction of force when load was applied at L5, with decreasing rotation as the force was applied in a more caudal direction. CONCLUSION: Posteroanterior stiffness in individuals without back pain is affected by the sagittal plane direction in which the posteroanterior force is applied to the lumbar spine. Remote (thoracic and sacral) movements are also affected by the direction of posteroanterior force. Direction of applied force should therefore be controlled, particularly in the research setting. PMID- 11208219 TI - Recruitment and accrual of women in a randomized controlled trial of spinal manipulation. AB - OBJECTIVE: To report on recruitment efforts and accrual rates for a nonmusculoskeletal chiropractic clinical trial. DESIGN: Information regarding the method of recruitment was collected for each individual who responded to an advertisement and completed an interviewer-administered telephone screening. SETTING: A suburban chiropractic teaching clinic with recruitment efforts extending throughout the larger metropolitan area. PATIENTS: A total of 2312 women were screened for participation and the advertisement source was noted for each. Of these, 138 women were recruited and fulfilled all study requirements. MAIN OUTCOME MEASURES: The numbers of responses and accrual rates were determined for 8 different recruitment methods: newspaper advertisements, community referrals, radio advertisements, community colleges, press releases, a community electronic sign, public television, and local posters. RESULTS: The most effective recruitment methods were newspaper advertisements, community referrals, and radio advertisements; the least effective methods were public television and local posters. CONCLUSIONS: The effort required for the recruitment of subjects was underestimated in this study. Based on the information gained, future recruitment methods for study participants will primarily focus on low-effort, high-yield methods such as newspaper and radio advertising, followed by press releases, campus electronic signs, and public television. PMID- 11208220 TI - Sources of variation in spinal indentation testing: indentation site relocation, intraabdominal pressure, subject movement, muscular response, and stiffness estimation. AB - BACKGROUND: Force-displacement properties of spinal tissues assessed by blunt indentation are thought to have clinical relevance; however, numerous variables with respect to spinal indentation have yet to be identified or characterized completely. OBJECTIVE: To identify and quantify, where possible, previously unidentified or incompletely characterized variables with respect to spinal indentation. DESIGN: Multiprotocol design. METHODS: Four experiments were performed: (1) Twelve asymptomatic subjects were indented with concurrent electromyography during conditions of rest, held inspiration, increased intraabdominal pressure and lumbar extension. (2) Changes in the recumbent position of 12 subjects were measured while a series of movements was performed in restrained and unrestrained conditions. (3) Ten clinicians attempted to locate, and to relocate, a subcutaneous anatomical landmark through visualization/palpation and ultrasonic imaging. (4) Performances of 3 methods of force-displacement curve modeling were compared with respect to stiffness estimation. RESULTS: (1) Spinal stiffness increased significantly in a minority of subjects awaiting indentation and in a majority of subjects during increases in intraabdominal pressure. (2) Changes in subject position were significantly reduced by a restraint system. (3) With respect to interclinician error in locating and relocating an indentation site, there was significant improvement with the use of ultrasonic visualization. (4) The error associated with linear techniques used to model curvilinear force-displacement data plots increased with increasing linear intervals. CONCLUSION: Several sources of variation in spinal indentation were identified: indentation site relocation, intraabdominal pressure, subject movement, muscular response, and stiffness estimation. These variables, which have been unaccounted for in previous indentation studies, might be responsible for the change or lack of change in force-displacement properties between preintervention and postintervention indentation trials. PMID- 11208221 TI - Patient characteristics and physicians' practice activities for patients with chronic low back pain: a practice-based study of primary care and chiropractic physicians. AB - BACKGROUND: Chronic low back pain sufferers are among those who account for the greatest usage of health care resources. Primary care medical (MD) physicians and chiropractic (DC) physicians treat most of these patients. OBJECTIVES: To study patient characteristics and physician practice activities for patients with chronic low back pain treated by DC physicians and MD physicians. METHODS: A longitudinal, practice-based observational study was undertaken in 14 general practice and 51 DC community-based clinics. A total of 2945 consecutive patients with ambulatory low back pain of mechanical origin were enrolled; 835 patients were in the chronic subgroup. Patients were followed for 12 months. Data were obtained on all of the following: patient demographics, health status, and psychosocial characteristics; history, duration, and severity of low back pain and disability; physicians' practice activities; and low back complaint status at 1 year. RESULTS: Patients treated by MD physicians were younger and had lower incomes; their care was more often paid for by a third party; their baseline pain and disability were slightly greater. In addition, patients treated by MD physicians had one fourth as many visits as patients treated by DC physicians. Utilization of imaging procedures by enrolling physicians was equivalent for the two provider groups. Medications were prescribed for 80% of the patients enrolled by MD physicians; spinal manipulation was administered to 84% of patients enrolled by DC physicians. Physical modalities, self-care education, exercise, and postural advice characterized low back pain management in both provider groups. Patients' care-seeking was not exclusive to one provider type. Most patients experienced recurrences (patients treated by MD physicians, 59.3%; patients treated by DC physicians, 76.4%); 34.1% of patients treated by MD physicians and 12.7% of patients treated by DC physicians reported 12 months of continuous pain. Only 6.7% of patients treated by MD physicians and 10.9% of patients treated by DC physicians reported 1 resolved episode during the year. CONCLUSIONS: Differences in sociodemographics, present pain intensity, and functional disability may distinguish patients with chronic low back pain seeking care from primary care medical physicians from those seeking care from DC physicians. Although the primary treatment modality differs, the practice activities of MD physicians and DC physicians have much in common. Long-term evaluation suggests that chronic back pain is persistent and difficult to treat for both provider types. PMID- 11208222 TI - Significant changes in systolic blood pressure post vectored upper cervical adjustment vs resting control groups: a possible effect of the cervicosympathetic and/or pressor reflex. AB - OBJECTIVE: To determine whether a vectored adjustment of the atlas in patients identified as demonstrating signs of upper cervical joint dysfunction would cause lowering of blood pressure in comparison with resting controls. DESIGN: Test 1: controlled clinical trial with a treatment (adjustment) group and a control (resting) group. Test 2: controlled clinical trial with subjects serving as their own controls. SETTING: Private chiropractic practice. PARTICIPANTS: Test 1: Forty established patients demonstrating signs of upper cervical subluxation/joint dysfunction and 40 established patients without such signs. Test 2: Thirty established patients demonstrating signs of upper cervical subluxation/joint dysfunction. INTERVENTION: Specific, vectored upper cervical (atlas) adjustment or similarly positioned resting. MAIN OUTCOME MEASURES: Prerest, postrest, and postadjustment systolic, diastolic, and pulse rates as recorded through use of a digital oscillometric sphygmomanometer. RESULTS: In test 1, subjects receiving adjustment had a significant (P <.001) decrease in systolic blood pressure whereas resting subjects did not. Intergroup comparison of the treatment (adjustment) and control (resting) groups demonstrated a significant difference (P <.001). A greater pre/post drop in systolic pressure was associated with greater age and higher initial systolic pressure. In test 2, the pre/postrest change in systolic blood pressure was not significant. The systolic blood pressure changed significantly (P <.001) from postrest readings to postadjustment readings. CONCLUSION: The results indicate that palpation and vectored atlas adjustment causes a significant decrease in systolic blood pressure in patients with putative upper cervical subluxation/joint dysfunction in comparison with resting controls. Similar results were also demonstrated when subjects acted as their own controls. The lack of randomization, blinding, and a manipulated control group are factors that weaken these findings. The sudden drop in systolic pressure is proposed to be due to stimulation of the cervicosympathetic reflex or moderation of muscle tone and elimination of the effects of the pressor reflex. PMID- 11208223 TI - Isometric back extension endurance tests: a review of the literature. AB - OBJECTIVE: To review the literature that describes and evaluates the use of isometric back extension endurance tests. DATA COLLECTION: Relevant articles in English were retrieved through a search of MEDLINE and the Index to Chiropractic Literature. Key search terms were back muscle endurance, isometric back endurance, trunk extensors, back muscle performance, and Sorensen test. DATA SYNTHESIS: The principal criterion for inclusion was as follows: any study that discussed or tested an isometric type of back endurance extension test. Studies that were excluded did not use an isometric testing protocol. Thirty-seven of the initial studies are included in this review. RESULTS: Six different types of isometric back extension endurance testing methods were found. Three of these procedures require special testing devices. Much of the research on this topic has centered on a procedure known as the Sorensen test. Normative databases have been established for the Sorensen test and 2 other test types. Validity and reliability have been assessed for some of the procedures. CONCLUSIONS: The influence of motivation and effort exerted by the subject are limiting factors in all of the tests reviewed. These psychologic factors warrant further research. On the basis of the literature reviewed, we determined that the Sorensen is probably the most clinically useful of these tests; it is easy to perform, requires no special equipment, and enjoys the most support from the literature. PMID- 11208224 TI - Missed lumbar transverse process fractures in a high school football player. AB - OBJECTIVE: To discuss the case of a football player who had suffered a transverse process fracture of the lumbar spine that was overlooked on initial chiropractic and medical examination. CLINICAL FEATURES: A 17-year-old male football player had been speared in the back by another player. He reported severe initial pain that caused him to fall to the ground, and there was a moderate degree of pain at the time of his chiropractic examination 1 week after injury. INTERVENTION AND OUTCOME: Initial chiropractic treatment consisted of spinal manipulation to the lumbar spine. Follow-up care consisted of lumbar spine radiographs that showed evidence of a lumbar transverse process fracture at 2 levels. The boy was referred to his medical doctor, who was not convinced of the presence of a fracture and returned him to play. A computed tomography scan was subsequently performed; this confirmed fractures of the transverse processes of L2 and L3. The patient was precluded from contact sports for 4 weeks. Chiropractic care 3 weeks after injury included physiotherapy and drop table mobilization to the sacroiliac joints. The patient returned to play 4 weeks after the injury. CONCLUSION: Transverse process fractures commonly occur secondary to blunt trauma in contact sports such as football. With high-force direct trauma, radiographs should be performed to rule out fracture before returning the athlete to play or commencing spinal manipulation. PMID- 11208225 TI - Dialysis-related spondyloarthropathy. AB - OBJECTIVE: To discuss a case of dialysis-related spondyloarthropathy due to beta 2 microglobulin amyloid deposition. An emphasis is placed on the imaging findings. CLINICAL FEATURES: A 67-year-old man sought treatment for low back pain. His history revealed coronary artery bypass surgery, diabetes with bilateral foot neuropathy, gout, and bilateral renal failure that had been treated with dialysis for 2 years before left renal transplantation; the renal transplant had been performed 6 years earlier. Radiography, computed tomography, and magnetic resonance imaging revealed changes characteristic of dialysis related spondyloarthropathy. INTERVETION AND OUTCOME: The patient was initially treated with physiotherapy. He was then admitted to the hospital and treated for renal infection and medicated for low back pain. Two weeks later he returned to the chiropractor, who began a treatment plan that included spinal manipulation, physiotherapy, manual distractive traction, and a gradual increase in activities of daily living. The patient was released from care after 2 months with significantly decreased pain. CONCLUSIONS: Dialysis-related spondyloarthropathy is a relatively uncommon complication of renal dialysis. It should be suspected in those patients who present with a correlative medical history and characteristic radiographic appearance. Chiropractic treatment can be effective as an adjunct to medical care in cases of chronic renal failure and associated complications. PMID- 11208226 TI - Evidence-based clinical guidelines submitted to the Australian National Health and Medical Research Council for the management of acute low back pain: a critical review. PMID- 11208227 TI - Sitting biomechanics, Part II: optimal car driver's seat and optimal driver's spinal model. PMID- 11208230 TI - A randomized controlled trial of chiropractic spinal manipulative therapy for migraines. PMID- 11208229 TI - A randomized controlled trial of chiropractic spinal manipulative therapy for migraines. PMID- 11208231 TI - Effects of orthotic intervention and 9 holes of simulated golf on club head velocity in experienced golfers. PMID- 11208233 TI - Reliability of chiropractic methods commonly used to detect manipulable lesions in patients with chronic low-back pain. PMID- 11208234 TI - The ten most commonly asked questions about infection as a cause of atherosclerotic heart disease. PMID- 11208235 TI - Mechanisms and management of paroxysmal supraventricular tachycardia. AB - Paroxysmal supraventricular tachycardia (PSVT) is defined as a regular rapid heart beat, which initiates and terminates suddenly. PSVT may have a variety of electrophysiologic mechanisms, including atrial tachycardia, atrioventricular (AV) nodal reentry, and tachycardia involving an accessory AV connection. Atrial tachycardia may be reentrant or may be caused by abnormal automaticity or triggered activity. AV nodal reentry, in which the reentrant circuit is confined to the AV node or the region around the AV node, is the most common type of PSVT in adults. Orthodromic supraventricular tachycardia is the most frequently found tachycardia in patients with accessory AV connections. During orthodromic supraventricular tachycardia, antegrade conduction occurs via the AV node, and retrograde conduction occurs via an accessory AV connection. Other types of PSVT, including junctional tachycardia, are less common. A definitive diagnosis of the PSVT mechanism usually requires electrophysiologic testing, but clinical and electrocardiographic clues may be present. Understanding the mechanism of PSVT can alter therapy because the response to antiarrhythmic drugs may be somewhat different depending on the PSVT type. In addition, the risks and efficacy of catheter ablation for curing PSVT may differ depending on the PSVT type. A better understanding of PSVT mechanisms, which has developed over the past 20 years, has led to dramatic improvements in therapy. PMID- 11208236 TI - What is commotio cordis? AB - Although thought to be rare, sudden deaths caused by nonpenetrating chest wall impact in the absence of structural injury to the ribs, sternum, and heart (commotio cordis) are reported with increasing frequency. This phenomenon is described in individuals when they are struck by relatively innocent blows to the chest wall. Young male athletes aged 5 to 18 years are particularly at risk for this catastrophe. It has been described after blows to the chest from baseballs, softballs, hockey pucks, and other objects. Death is usually instantaneous, and successful resuscitation is uncommon. A recently reported experimental model provides clues to the mechanisms and inferences for the prevention and treatment of this devastating condition. This swine model shows that a) ventricular fibrillation results from low-energy chest wall impacts during a vulnerable period of repolarization, b) the risk of this event can be decreased with softer than-standard baseballs, and c) prompt defibrillation is crucial for resuscitation to be successful. PMID- 11208237 TI - Intraoperative transesophageal echocardiography: correlation of echocardiographic findings and surgical pathology. AB - Before the introduction of transesophageal echocardiography (TEE) in the operating room, intraoperative echocardiography relied on epicardial imaging. The disadvantages of this approach included interference with the surgical procedure, limited windows, and potential distortion of cardiac structures. Consequently, multiplane TEE has now emerged as the intraoperative imaging method of choice. It provides high-resolution images of cardiac structures and excellent portraits of flow abnormalities. Intraoperative TEE does not interfere with the surgical field and procedure. TEE provides better imaging of the valves, atria, aorta, pulmonic vasculature, and pericardium, which are sometimes difficult to visualize by transthoracic echocardiography. TEE is especially beneficial in surgeries for valve replacement, valve repair, cardiac mass, aortic disease, congenital heart disease, and pericardial disease. Presurgical TEE provides information for surgical planning. TEE is helpful for the assessment of the immediate result of surgery and detection of complications that may need a prompt response. Thus, intraoperative TEE has a vital impact on management of cardiac surgery. PMID- 11208238 TI - Outpatient management of heart failure. AB - The outpatient treatment of heart failure can be divided into 2 broad categories: older therapies, which improve hemodynamics, and newer therapies, which increase survival and improve function. Hemodynamic "triple" therapy includes digoxin to increase cardiac inotropy, antihypertensives to lower systolic pressure, and diuretics to remove fluid and decrease filling pressures. Disease-modifying therapy requires the use of specific agents to lower blood pressure (angiotensin converting enzyme inhibitors, angiotensin II blockers, spironolactone, or hydralazine and nitrates) and beta-adrenergic blockade with carvedilol. The success of these newer therapies suggests that the standard triple therapy for heart failure should be expanded to "quadruple" therapy that includes carvedilol. PMID- 11208239 TI - The dietary approaches to stop hypertension (DASH) clinical trial: implications for lifestyle modifications in the treatment of hypertensive patients. AB - Lifestyle modifications, such as weight loss, sodium restriction, and limiting alcohol consumption, are important components of the initial treatment of hypertensive patients. The Dietary Approaches to Stop Hypertension (DASH) study investigated the effects of dietary patterns on blood pressure in individuals with diastolic blood pressure between 80-95 mmHg. Two different dietary patterns were tested in this feeding study. A diet enriched in fruits and vegetables and a diet enriched in fruits, vegetables, and low-fat dairy products and low in total and saturated fat (combination diet) were compared with a control diet. Dietary intake was adjusted so that participants did not lose weight, and all study diets had comparable sodium intake (approximately 3 grams/day). All meals were provided for 459 participants for an 11-week period. Those randomized to the combination diet (n = 151) had a significant change in systolic (-5.5 mmHg; p < 0.001) and diastolic blood pressure (-3.0 mmHg; p < 0.001) after subtracting the response to the control diet (n = 154). The fruits-and-vegetables diet (n = 154) produced a significant but lesser decrease in blood pressure (systolic, -2.8 mmHg; p < 0.001 and diastolic, -1.1 mmHg; p = 0.07). Hypertensive individuals and African Americans had particularly favorable responses with blood pressure reductions, which were significantly greater than other subgroups. The combination diet was well-accepted and adherence to the diet was high (>90%) for all participants. The DASH combination diet is an effective lifestyle modification for lowering blood pressure in patients with high-normal or Stage 1 hypertension. PMID- 11208240 TI - Application of intravascular ultrasound imaging in understanding and guiding percutaneous therapy for atherosclerotic coronary disease. AB - Intravascular ultrasound imaging is a relatively new imaging modality that uses miniaturized ultrasound transducers, which are mounted on catheter tips and introduced into the vessel lumen to provide cross-sectional images of the vascular structure in real time. It has gained popularity rapidly among interventional cardiologists because of its ability to overcome many limitations of angiography, especially when dealing with complex anatomy and new devices for coronary revascularization. The tomographic perspective and the ability to elicit the detailed structure of the arterial wall have allowed the use of intravascular ultrasound to better understand the coronary atherosclerotic and allograft vasculopathy disease processes. The response of lesions to various interventional procedures also has been studied in detail. This review discusses the rationale, technique, methods of interpretation, and the current knowledge in the field of intravascular ultrasound imaging. PMID- 11208241 TI - Exercise and heart disease in women: why, how, and how much? AB - Despite a traditional view that cardiovascular disease primarily affects men, a growing body of information now recognizes that it is a disease that equally affects women and is the leading cause of morbidity and mortality in women in the United States. Both physical activity and physical fitness have been shown to have an inverse association with coronary heart disease and cardiovascular risk factors. Furthermore, physical inactivity is now recognized by the American Heart Association as an independent risk factor for coronary heart disease. However, national surveillance programs have reported that 1/4 of adults are currently sedentary, and 1/3 of women do not engage in any leisure-time physical activity. Regular exercise may significantly impact coronary heart disease in women, as some coronary risk factors have a stronger predictive value for coronary heart disease in women as compared with men. Recent studies have shown that women who exercise regularly are less likely to develop diabetes mellitus; exercise may reduce blood pressure and produce improvements in lipid profiles. Conflicting data exist regarding the dose and intensity of exercise necessary to achieve significant health benefits; however, many reports demonstrate a reduced risk of mortality from cardiovascular diseases and from all causes with only moderate intensity physical activity. The Centers for Disease Control, American Heart Association, and American College of Sports Medicine recommend a regular pattern of physical activity of moderate intensity, which can be accumulated throughout the day and should be performed at least 3 to 5 days per week. In addition, the benefit of weight-bearing exercise should be underscored in women, because it plays an important role in the prevention and treatment of osteoporosis. Continued efforts are necessary to encourage the many American women who are currently inactive to make even modest increases in levels of physical activity to achieve substantial cardiovascular, as well as other, health benefits. PMID- 11208242 TI - The ten most commonly asked questions about pericardial disease. PMID- 11208243 TI - Alcohol septal ablation for hypertrophic obstructive cardiomyopathy. AB - Until the early 1990s, surgical myectomy was the standard treatment for patients with hypertrophic obstructive cardiomyopathy and drug refractory symptoms. In the past few years, the potential therapeutic options have dramatically changed with the introduction of DDD-pacemaker implantation and percutaneous transluminal septal myocardial ablation by alcohol-induced septal branch occlusion. The circumscribed therapeutic myocardial infarction results in widening of the left ventricular outflow tract with consecutive gradient reduction. Follow-up studies show impressive clinical improvement, as well as further gradient reduction as a result of left ventricular remodeling. In this article, we provide an updated review of the latest results of percutaneous transluminal septal myocardial ablation. PMID- 11208244 TI - Gene therapy for restenosis after balloon angioplasty and stenting. AB - Percutaneous coronary revascularization is an increasingly attractive alternative to medical therapy and surgical revascularization for coronary artery disease. The leading drawback of this procedure continues to be restenosis-the process of late arterial renarrowing at the site of initially successful intervention. Restenosis after balloon angioplasty seems to be determined primarily by the direction and magnitude of vessel wall remodeling. In contrast, the major limitation of stent implantation is the initiation of neointimal tissue proliferation within and adjacent to the stent. The goal of this review is to summarize recent laboratory and clinical investigations of the transmission of mitogenic signals from the membrane to the nucleus in smooth muscle cells. The mechanisms responsible for restenosis after balloon angioplasty and stenting and the possibility of transferring specific genes into somatic vascular cells with molecular tools to inhibit smooth muscle cell proliferation also will be reviewed. PMID- 11208246 TI - Hypertriglyceridemia and coronaryheart disease risk. AB - Several angiographic-based trials have established that triglyceride remnant particles are associated with progression of coronary stenosis, and a recent prospective study has shown that triglycerides are associated with coronary heart disease (CHD), even after adjustment for high-density lipoprotein cholesterol. The importance of plasma triglycerides in CHD risk must be interpreted within the context of other plasma lipoproteins, as well as the fasting and postprandial triglyceride levels. Recommendations for triglyceride lowering are empiric because of the lack of randomized clinical trial data that evaluate triglyceride lowering therapies and CHD prevention. This article presents a clinical approach to the management of hypertriglyceridemia. PMID- 11208245 TI - Therapeutic management of patients with Marfan syndrome: focus on cardiovascular involvement. AB - Marfan syndrome is an autosomal dominant disorder of the connective tissues, with mutation on the fibrillin-1 gene encoding for fibrillin, a major component of the extracellular microfibrils. The prevalence of the syndrome is 7 to 17 in 100,000. The mean life expectancy for untreated patients with Marfan syndrome is 32 years, with aortic dissection, aortic rupture, or cardiac failure from mitral or aortic valve regurgitation as the predominant cause of death in >90% of patients. However, with optimal clinical management of patients with Marfan syndrome, life expectancy may be improved substantially to a nearly normal life span. Cornerstones of clinical management include modern noninvasive imaging modalities, molecular analysis at the complementary deoxyribonucleic acid/deoxyribonucleic acid level of the fibrillin-1 gene, genetic counseling, lifestyle changes, and cardiovascular surveillance, the latter including regular imaging of the aorta and endocarditis prophylaxis. Prophylactic use of beta blocking agents, the timing of elective surgery, and the optimal surgical technique are difficult issues that need to be evaluated individually. Juvenile, postoperative, and pregnant patients with Marfan syndrome pose particular problems. The goal of this review is to facilitate differential decision-making based on referenced evidence and to provide guidelines for medical and surgical therapeutic strategies. PMID- 11208247 TI - Cardiac transplantation for end-stage heart disease. AB - In the nearly 30 years since the first successful human heart transplant, a variety of developments have allowed this form of cardiac replacement therapy to flourish. These have included improvements in surgical and critical care technology, as well as breakthroughs in immunosuppressive pharmacology, the most notable of which was the introduction of cyclosporine in 1980. Subsequently, indications and exclusion criteria for heart transplantation have evolved, guided by the constraints of a limited donor supply and facilitated by an improved understanding of prognostic risk factors. Current 1- and 5-year survival estimates are encouraging, and despite the frequency of acute rejection, current management strategies have, for the most part, limited the fatal consequences of this complication. Graft atherosclerosis, however, has continued to complicate the posttransplant course of many patients, and despite therapeutic strategies aimed at a variety of potential pathogenic mechanisms, this entity remains the most common cause of late death after transplantation. In these patients and other victims of allograft failure, retransplantation remains a viable option. Finally, the recent trend of selecting increasingly critically ill transplant recipients, although not associated with inferior survival, has driven the costs of this form of cardiac replacement therapy to unprecedented levels. These issues, as well as current developments in the fields of mechanical cardiac assistance, xenotransplantation, and cardiac gene therapy, will certainly result in a continually evolving role for cardiac transplantation in the treatment of end-stage heart disease. PMID- 11208248 TI - Appetite-suppressing drugs and valvular heart disease. AB - The popular diet drugs, fenfluramine and dexfenfluramine, were withdrawn from the market in the United States after the publication of an association of these drugs with valvulopathy in a small series of patients, spontaneous reports to the Food and Drug Administration, and echocardiographic surveys that suggested a valvulopathy prevalence of 32.8% among diet drug users. Subsequent publications suggested that there is an association of these agents with valvulopathy, but that the prevalence seems lower than initially suspected. This review examines the available prevalence data and attempts to account for some of the variability in these data. Potential pathophysiologic mechanisms are discussed and management guidelines for these patients are provided. This is an area of ongoing study and more information about the natural history of these lesions will certainly be forthcoming. A review of the data reveals that the withdrawal of these agents was prudent and likely prevented further harm. PMID- 11208249 TI - Gender differences in manifestation of cardiac arrhythmias. AB - It is now appreciated that a patient's sex has a significant impact on presentation of cardiac diseases. This has been well described in patients with coronary artery disease but is less well appreciated in the setting of arrhythmia management. In Cardiology in Review in 1998, Tracy outlined some of the major differences between the sexes with regard to the electrocardiogram and the presentation of arrhythmias. Arrhythmia management also can be considerably different, and in this review, we address some additional aspects of differences between the sexes in this area. PMID- 11208250 TI - The ten most commonly asked questions about echocardiography: part 2. PMID- 11208251 TI - Mitral valve surgery with concomitant treatment of atrial fibrillation. AB - Recovery of sinus rhythm after mitral valve surgery in patients with chronic atrial fibrillation lowers thromboembolic risk and improves survival and quality of life. This article reviews the principal surgical procedures devised in the 1980s and 1990s to treat atrial fibrillation during mitral valve operations. Advantages and drawbacks of the different techniques are discussed. Traditional atrial fibrillation surgery is technically demanding and increases operative morbidity. Simplified techniques, mostly limited to the left atrium, have been developed to reduce operation time and procedure-related complications. Intraoperative radiofrequency ablation has recently proven extremely effective in atrial fibrillation surgery, allowing a further simplification of the procedures. We report the results of an original technique for atrial fibrillation treatment during mitral valve surgery through epicardial radiofrequency ablation. Based on recently reported results of atrial fibrillation surgery and on prognostic considerations, specific treatment of both chronic and paroxysmal atrial fibrillation is indicated in virtually all affected patients undergoing mitral valve surgery. PMID- 11208252 TI - Carotid and cerebrovascular disease. AB - Stroke remains a major public health problem, and carotid artery atherosclerotic disease causes a significant proportion of all strokes. Because the U.S. population is aging, the incidence of cerebrovascular disease is increasing, and cardiologists often are involved in the care of these patients because many of them have either occult or symptomatic coronary artery disease. We review the current status of carotid and cerebrovascular diseases and therapeutic options. PMID- 11208253 TI - Aortic valve surgery in the elderly. AB - As the population ages, aortic valve replacement, particularly for aortic stenosis, has become more common. Although many patients have considerable coexisting morbidity, almost all symptomatic patients are candidates for surgery. Once symptoms develop, surgery should not be unduly delayed, because the operative mortality clearly increases in the presence of poor left ventricular function, heart failure, and New York Heart Association Class III or IV symptoms. Operative difficulties often are related to fragile tissues, a small aortic annulus, and extensive calcification of the aortic annulus and root. In the author's experience, approximately 10% of these patients undergo aortic annulus and root enlargement using pericardium. A tissue valve is the preferred prosthesis. Operative mortality for elective surgery in patients older than 80 years of age is 4-10%, depending on whether associated procedures are required (eg, coronary artery bypass grafting) or whether the patient has had previous surgery. Postoperative neurologic events are important complications that are more common in the elderly. Outcome after successful surgery is excellent, with a 5-year survival of approximately 60%. The vast majority of patients have an improved symptomatic status. PMID- 11208254 TI - Overview of recent clinical trials in heart failure: what is the current standard of care? AB - Heart failure develops as a consequence of cardiac injury. As the heart begins to fail to meet the body's metabolic demands, the renin angiotensin aldosterone system (RAAS) and the sympathetic nervous system are activated. These interrelated systems act in concert to facilitate cardiac output and tissue perfusion. Though these neurohormonal systems are initially compensatory, evidence suggests that they promote deleterious cardiac remodeling and myocyte destruction. Recent studies in patients with heart failure have targeted the RAAS and sympathetic nervous system for therapeutic intervention. This article reviews major recent multicenter, randomized, double-blind, and placebo-controlled trials in heart failure that have resulted in a new standard of care for patients with this devastating disease. PMID- 11208255 TI - Role of glycoprotein IIb/IIIa inhibitors in unstable angina: current perspectives. PMID- 11208256 TI - Noninvasive diagnostic testing of coronary artery disease in women. AB - Noninvasive diagnostic testing of coronary artery disease (CAD) is widely recognized as an area that is less studied and less accurate with regard to women than to men. Accurate and safe diagnostic testing constitutes the crucial link between early detection and optimal management of CAD. Many noninvasive diagnostic modalities are available to the clinician, including traditional electrocardiography, the relatively novel imaging of echocardiography, the emerging nuclear perfusion technology of electron beam computed tomography, exercise testing, and pharmacologic testing. The most accurate and cost-effective diagnostic method for patients depends on the patients' pretest likelihood of the disease as determined by factors such as sex, age, and cardiovascular risk factors. Noninvasive tests are most useful in the diagnosis of CAD in patients with intermediate pretest likelihood of CAD. Patients with low pretest likelihood of CAD with normal electrocardiograms may benefit from noninvasive tests or a watchful waiting strategy. Patients with a high pretest likelihood of CAD may benefit greatly from direct referral to coronary angiography. Among the noninvasive diagnostic methods, exercise electrocardiography is the most studied and least accurate with regard to women patients. Electrocardiography improves in accuracy when combined with imaging techniques such as echocardiography or nuclear single photon emission computed tomography. Combining data from all studies has shown that exercise echocardiography yields the highest diagnostic accuracy in women among all of the exercise stress tests. Patients who are unable to achieve maximal exercise capacity may undergo pharmacologic testing using dipyridamole or adenosine radionuclide perfusion or dobutamine echocardiography. Recent development of electron beam computed tomography accurately detects coronary artery calcium but has not been validated yet as a standard diagnostic test for CAD. PMID- 11208257 TI - The viral transmembrane superfamily: possible divergence of Arenavirus and Filovirus glycoproteins from a common RNA virus ancestor. AB - BACKGROUND: Recent studies of viral entry proteins from influenza, measles, human immunodeficiency virus, type 1 (HIV-1), and Ebola virus have shown, first with molecular modeling, and then X-ray crystallographic or other biophysical studies, that these disparate viruses share a coiled-coil type of entry protein. RESULTS: Structural models of the transmembrane glycoproteins (GP-2) of the Arenaviruses, lymphochoriomeningitis virus (LCMV) and Lassa fever virus, are presented, based on consistent structural propensities despite variation in the amino acid sequence. The principal features of the model, a hydrophobic amino terminus, and two antiparallel helices separated by a glycosylated, antigenic apex, are common to a number of otherwise disparate families of enveloped RNA viruses. Within the first amphipathic helix, demonstrable by circular dichroism of a peptide fragment, there is a highly conserved heptad repeat pattern proposed to mediate multimerization by coiled-coil interactions. The amino terminal 18 amino acids are 28% identical and 50% highly similar to the corresponding region of Ebola, a member of the Filovirus family. Within the second, charged helix just prior to membrane insertion there is also high similarity over the central 18 amino acids in corresponding regions of Lassa and Ebola, which may be further related to the similar region of HIV-1 defining a potent antiviral peptide analogue. CONCLUSIONS: These findings indicate a common pattern of structure and function among viral transmembrane fusion proteins from a number of virus families. Such a pattern may define a viral transmembrane superfamily that evolved from a common precursor eons ago. PMID- 11208258 TI - Endemic and epidemic dynamics of cholera: the role of the aquatic reservoir. AB - BACKGROUND: In the last decades, attention to cholera epidemiology increased, as cholera epidemics became a worldwide health problem. Detailed investigation of V. cholerae interactions with its host and with other organisms in the environment suggests that cholera dynamics is much more complex than previously thought. Here, I formulate a mathematical model of cholera epidemiology that incorporates an environmental reservoir of V. cholerae. The objective is to explore the role of the aquatic reservoir on the persistence of endemic cholera as well as to define minimum conditions for the development of epidemic and endemic cholera. RESULTS: The reproduction rate of cholera in a community is defined by the product of social and environmental factors. The importance of the aquatic reservoir depends on the sanitary conditions of the community. Seasonal variations of contact rates force a cyclical pattern of cholera outbreaks, as observed in some cholera-endemic communities. CONCLUSIONS: Further development on cholera modeling requires a better understanding of V. cholerae ecology and epidemiology. We need estimates of the prevalence of V. cholerae infection in endemic populations as well as a better description of the relationship between dose and virulence. PMID- 11208259 TI - Symptomatic hemorrhage after alteplase therapy not due to silent ischemia. AB - BACKGROUND: Stroke thrombolysis-related intracerebral hemorrhage may occur remotely from the anatomical site of ischemia. One postulated mechanism for this is simultaneous multiple embolization with hemorrhage into a "silent" area of ischemia. RESULTS: A patient suffered a disabling stroke affecting the right cerebral hemisphere. He was treated with intravenous alteplase and underwent extensive early imaging with multimodal MRI. Several hours after treatment he developed a brainstem hemorrhage despite having no evidence of ischemia on DWI MRI in the brainstem. CONCLUSION: Not all occurrences of remote ICH after stroke thrombolysis are secondary to multiple emboli with silent ischemia. PMID- 11208261 TI - [Results of the first phase of the ECVAM project "prevalidation and validation of three in vitro embryotoxicity tests"] AB - The results of the experimental prevalidation of three in vitro embryotoxicity tests in an ECVAM study are reported: the rat whole embryo culture assay (WEC), the micromass assay (MM) and the embryonic stem cell test (EST). Three test chemicals assigned to the three classes of embryotoxicity, non-, moderate- and strong embryotoxic, and also a positive and a negative control chemical were repeatedly tested in each test in two laboratories. The data obtained were evaluated independently by a biostatistician. It could be shown that the standard protocols (SOPs) for the three in vitro embryotoxicity tests could be transferred to a second laboratory and that reproducible results were obtained. The three methods were able to discriminate the test chemicals according to their embryotoxic potential. In addition, within the scope of this study, a test chemical database for in vitro embryotoxicity testing was established that will be used in the following formal validation of the three in vitro tests. PMID- 11208260 TI - The potential for research-based information in public health: identifying unrecognised information needs. AB - OBJECTIVE: To explore whether there is a potential for greater use of research based information in public health practice in a local setting. Secondly, if research-based information is relevant, to explore the extent to which this generates questioning behaviour. DESIGN: Qualitative study using focus group discussions, observation and interviews. SETTING: Public health practices in Norway. PARTICIPANTS: 52 public health practitioners. RESULTS: In general, the public health practitioners had a positive attitude towards research-based information, but believed that they had few cases requiring this type of information. They did say, however, that there might be a potential for greater use. During five focus groups and six observation days we identified 28 questions/cases where it would have been appropriate to seek out research evidence according to our definition. Three of the public health practitioners identified three of these 28 cases as questions for which research-based information could have been relevant. This gap is interpreted as representing unrecognised information needs. CONCLUSIONS: There is an unrealised potential in public health practice for more frequent and extensive use of research-based information. The practitioners did not appear to reflect on the need for scientific information when faced with new cases and few questions of this type were generated. PMID- 11208262 TI - [Liver organ systems: valuation by gene expression] AB - The multitude of vital functions of the liver is largely dependent on the complex interaction of hepatocytes with "littoral-cells" and the liver-specific extracellular matrix. In vitro systems used to study the liver are almost exclusively based on the culture of single cells obtained by enzymatic disruption of the essentiel organ structure. In contrast, the slicing technique enables a standardized organ culture, while retaining the intact organ structure. However, previous experiments using this system have been restricted to short-term pharmacological studies and have used general cellular parameters to assess viability. The lack of liver specific validation has hindered the acceptance and application of this organ culture as an alternative to in vivo experiments. In this work we chose the regulation of liver-specific gene expression as an adequate viability criterion because, in contrast to the commonly used general cell physiology parameters, gene expression includes a cascade of differentially coordinated processes. Using hormonal responsiveness of precision-cut liver slices as a basis for comparison, the new developed interphase system was found to be superior to a perfusion system. With the application of this economical and easy-to-handle interphase system, the control of liver-specific gene expression by dexamethasone, cAMP and endotoxin in long-term cultures was found to be modulated in a manner similar to in vivo conditions. PMID- 11208263 TI - [ERGATT/ECVAM Workshop on Acceptance of Validated Alternative Methods: Amden III] AB - Since validated in vitro toxicity tests have so far not been accepted by regulators the third international ERGATT/ECVAM validation workshop was held from January 26-30, 1998, in Amden/Switzerland. Scientific and political reasons for a delay of the acceptance of alternative methods were identified in the areas of phototoxicity, skin penetration and skin corrosivity and strategies to promote the acceptance were suggested. The OECD will harmonise the formal of criteria for the regulatory acceptance of new experimentally validated tests and of established tests from industry for which in-house and literature data exist. In vitro tests for phototoxicity and skin penetration will be accepted shortly by the OECD. For skin corrosivity two in vitro tests will be put forward to the OECD later this year. The Amden III workshop suggests that, the same acceptance criteria must be used for animal and in vitro tests. Finally, the OECD should remove tests that cause pain and distress to test animals from the official OECD list of official test guidelines if validated alternative methods exist. When obsolete animal tests are taken from the list of official OECD test guidelines, they will not any longer be accepted at the international level. Thus, the third Amden workshop has contributed new concepts for the regulatory acceptance of alternative toxicity tests which are supported by regulators in Europe, the USA and the OECD. PMID- 11208264 TI - [Use of transgenic animals in the European Union] AB - Transgenic animals present unique possibilities for medical, agricultural and fundamental research, and as a means of producing valuable pharmaceutical and nutrient products. Their use has increased dramatically in recent years and is set to increase further in the near future. It has been claimed that transgenic animals might allow reduction and refinement in animal use, via more-precise gene targeting in breeding programmes. However, these objectives are threatened by transgenic procedures which may promote greater animal use, more-varied applications, and the greater likelihood of animal suffering. Current legislation on animal experimentation, for example, Directive 86/609/EU, was passed and implemented before the full implications of transgenesis were recognised. For this reason, ECVAM organised a workshop which was held in Southwell, Nottinghamshire, UK, on 7-11 April 1997. The aim of this workshop was to reach a consensus on a set of guidelines designed to assist regulatory authorities in their decision-making process. The conclusions of the workshop are subdivided into general considerations, proposals to use transgenic animals, production and use of transgenic animals, specific considerations relating to animals used as basic research/disease models, animals used in testing for toxicity and carcinogenicity, and transgenic farm animals. 14 recommendations have been derived from these conclusions and should make an important contribution to ensuring that the interests and welfare of animals are given due respect. They demonstrate a willingness by scientists to respond to public concerns and they should facilitate a consistent, harmonised and equitable regulatory approach within the EU. PMID- 11208265 TI - [Transgenic Animals within the 3R concept] AB - There are positive examples of transgenic animals where transgenic technology has allowed the use of less animals to answer a specific research question. On the other hand, it requires large numbers of animals to produce transgenic strains. And there remains the question, when these animals show clinical signs of disease, if they suffer more or less than their "pretransgenic" counterparts. To what extent transgenic animals further the cause of the 3Rs must be evaluated on an individual basis. PMID- 11208266 TI - [Transgenic animals and animal welfare] AB - Under the pressure of a public vote in Switzerland (7 June 1998) on an initiative to ban the production, use and patenting of transgenic animals, their value for biomedical research and development is intensely debated. In addition, the Swiss legislation has adopted (1992) a constitutional obligation to "take into account the dignity of creatures". The term "dignity of creatures", however, can be interpreted in anthropocentric or biocentric ways. The government has now formulated the legal implications of this term for transgenic animals and plants in various laws including the animal and environmental protection laws. This paper gives arguments for a fair evaluation of trangenic animals from an animal welfare point of view where not only the costs of animal suffering must be considered but also the probability of potential benefit for man. A self confident research community should allow such an evaluation procedure even in view of an outcome which could ban many uses of transgenic animals PMID- 11208267 TI - [Animal welfare problems concerning the use of transgenic animals] AB - Using transgenic animals as clinical models pose certain problems since they can suffer. Yet in single cases transgenic animals can reduce the suffering of (other) animals. The permission to generate transgenic animals is not yet clearly regulated in Switzerland. The term "dignity of creature", as formulated in the Swiss Constitution, has to be defined for the Swiss animal protection law. We present the recommendations of the commission for ethical questions concerning transgenic animals appointed by the Federal Council. Partly, these recommendations shall also be applied to the traditional breeding methods. We support the nomination of a national ethics committee for transgenic animals. PMID- 11208268 TI - [Ethical Problems of Cross-Species Transplantation from Animals to Humans] AB - The success of transplantation and the increasing demand for donor organs have led to an increasingly acute shortage of human organs and tissue for transplantation. In this situation xeno-transplantation is discussed as a possible alternative to allo-transplantation. Cross-species transplantation however involves certains risks and ethical problems, some of which are thematized in this abstract. PMID- 11208269 TI - [Xenotransplantation and animal welfare] AB - The problems of feasibility and public acceptance of using animals as foreign donors for organ transplants (xenotransplantation) are discussed from an animal protection point of view. It is proposed that a transparent information and a transdisciplinary composition of the members of decisive bodies is ensured to incorporate the current distrust towards xenotransplantation of a large part of the population. This strategy could lead to a consensus for or against such animal use of the whole society before it is technically possible and therefore irrevocable facts are created. PMID- 11208270 TI - [Komitee fur Tiergesundheit und. Teil II] PMID- 11208271 TI - [Alternative methods to animal experimentation lead to the discovery of a novel inflammation factor] AB - Simple testing models have been developed for the evaluation of chemical or biological compounds that influence the activity of leukocytes. Human blood neutrophil leukocytes are used. They are stimulated in various ways, and the effects of test compounds on the release of enzymes, the generation of oxygen radicals and cell damage are quantified. All assays are performed in microtiter plates and the responses are evaluated by multi-well photometry or fluorimetry. The models are apt to detect compounds acting on leukocytes as stimuli, inhibitors, and response modifiers. The use of these methods led to the discovery of a novel inflammatory peptide, NAP-1, which activates neutrophil leukocytes. NAP-1 consists of 72 amino acids and is generated by a variety of tissue cells. PMID- 11208272 TI - [Monoclonal antibodies: in vivo- and in vitro-production in laboratory scale with consideration of the legal aspects of animal protection] AB - Monoclonal antibodies are valuable tools in medical and biological research which can be used for identifying, characterizing and purifying medically and biologically important substances. Due to their high specificity monoclonal antibodies are more and more used in the diagnosis and therapy of infectious diseases and tumor illnesses. Large amounts of antibodies are needed for use in these areas and this necessitates mass production (g - kg range). Many production systems and possibilities for optimizing mass production have been described. In contrast, at universities and other research institutions the production of monoclonal antibodies in laboratory scale (mg range) is still carried out mostly in the ascites mouse. This article described our own experiences and results with the in vitro production in mg range. Using the German animal protection law (22.8.1986) as an example the legal aspects of animal protection in the production of monoclonal antibodies are discussed. In addition the legal regulations in Switzerland and the Netherlands are presented. PMID- 11208273 TI - [Testing the acute toxicity of chemicals using bacteria] AB - Two bacterial tests are used to screen the acute toxicity of 8 compounds which are known as pollutants in the air of stables. The procedures applied were batch microcalorimetry (E.coli) and the Microtox(R)-test (P. phosphoreum). It is shown that both bacterial "screening models" are suitable to evaluate the acute toxicity of the compounds tested. The test results are compared to results from other toxicity tests using higher developed organisms; additionally the comparison included compounds from the literature. It is found that the results from the different test systems are significantly correlated as far as linear correlation and as rank correlation are concerned. The range of the results supports the suggestion to apply two or more short-term tests involving different test organisms in a "test battery". Bacterial short-term assays may not completely replace experiments involving animals but they allow an estimation of the toxic potential of substances which have not yet been tested and may thus reduce the necessary amount of experiments with animals. PMID- 11208274 TI - [Potency testing of veterinary vaccines, rabies vaccines as an example] AB - Vaccines which are produced commercially should be controlled with respect to their efficacy (potency) and their "harmlessness" to the recipient animal. The basis for any potency test is the protection test in the target animal species. When a vaccine has been shown to be capable of protecting a particular species from a certain disease, alternative methods for potency testing often can be developed. The justification of the latter is that experiments which analyze the protection are cost-intensive, require a large number of animals and give only a moderate degree of reproducibility. Methods such as protection experiments in laboratory animals, the induction of the substances responsible for protection (such as antibodies) in target or laboratory animals as well as with in vitro tissue culture systems, or the quantitative determination of the immunogens (the components of a vaccine which should be responsible for protection) may be used only if their results correlate with those obtained from protection experiments in the target animal species. Rabies glycoprotein has been implicated as the main agent responsible for the induction of protection against rabies. The higher the content of glycoprotein in a rabies vaccine, the greater will be the potential of the vaccine to induce protection against the disease. Analyses of the rabies glycoprotein content in vaccines can make use of a number of methods which have proven acceptable (the immunodiffusion test, the antibody binding assay and the ELISA). However, in veterinary medicine most vaccines are associated with an adjuvant - a substance which should amplify the immune response of an animal against a vaccine. Since the adjuvants and vaccines in such preparations are inseparable, the presence of an adjuvant in a vaccine reduces the applicability of many in vitro methods. Thus, the above mentioned methods and possibilities for their adaptation to the analysis of adjuvanted vaccines will be discussed. PMID- 11208275 TI - Solving pathophysiological problems. AB - The aim of this paper was to analyze particular aspects of problem solving in pathophysiology. It is related to various kinds of knowledge presentation (textbook-type descriptions and computer programs) that are important for reasoning. PMID- 11208276 TI - Factors influencing the cellular location of proteolytic enzymes of Bacillus intermedius. AB - Thiol-dependent serine proteinase and glutamylendopeptidase of Bacillus intermedius 3-19 being prevailing enzymes in the total pool of extracellular proteinases (95%) of this microorganism in catalytic active form were detected on the membrane of the cells. Production of these enzymes was maximum on the medium containing inorganic phosphate and gelatin and decreased 2-4-fold on the medium with glucose and lactate. The level of the activity of extracellular enzymes correlated with that of corresponding membrane-bound proteins. The addition of CoCl2 (2 mM) into the medium caused essential increase in extracellular glutamylendopeptidase activity and promoted the release of membrane-bound enzyme into cultural fluid. Proteolytic activity was detected in cytoplasm also. Proteinases localized in cytoplasm were shown to differ in properties from those secreted. PMID- 11208277 TI - Soluble interleukin-6 receptor in plasma and in lymphocyte culture supernatants of healthy individuals and patients with systemic lupus erythematosus and rheumatoid arthritis. AB - The soluble IL-6 receptor (sIL-6R) occurring in various body fluids of healthy persons and patients with various diseases is an agonist since its complex with IL-6 binds to gp130 making IL-6 receptor negative cells responsive for IL-6. The generation as well as the functional role of soluble IL-6 receptor is poorly understood. We measured the sIL-6R levels by ELISA sandwich technology in sera and in supernatants of lymphocyte cultures without and after incubations with dexamethasone. Our results indicate, that the sIL-6R levels in sera of patients with inactive systemic lupus erythematosus (SLE) and active rheumatoid arthritis (RA) were higher than those of the control group, active SLE and inactive RA. In vitro dexamethasone treatment stimulated generation of sIL-6R in both healthy persons and in active SLE, however it strongly suppressed sIL-6R in both RA groups. At mRNA level, we found that in SLE both the mRNA coding the cell-bound and an alternatively spliced variant corresponding to soluble IL-6R transcript increases, however the strong decrease of sIL6R protein in RA was not found at mRNA level. PMID- 11208278 TI - Comparative morphology of the hepatic and coronary artery walls. Part I. Differences in the distribution and intensity of non-atherosclerotic intimal thickening and atherosclerosis. AB - We compared the morphology of the hepatic artery intima which is free of atherosclerosis, with that of the typically atherosclerosis-prone coronary artery. The study group comprised material collected from 116 autopsies. Subjects were aged between 1 month and 90 years. Specimens were collected from grossly normal arterial segments. An already known fact was confirmed: the presence and remarkable intensity of non-atherosclerotic intimal thickening in the coronary arteries since the beginning of life. On the contrary, hepatic artery intimal thickening was incidental during the first 4 decades of life and regular later on. During all the decades intimal thickness was decreased in the hepatic artery in comparison to the coronary artery. Initial atherosclerosis was noted during the 4th decade of life in the coronary artery and during the 8th and 9th decades in the hepatic artery. Intimal thickness was always lower in women compared to men. These findings reveal a positive correlation between the intensity of intimal hyperplasia and the incidence of atherosclerosis. The intimal pattern is of limited value in the determination of an unidentified subject age who underwent an autopsy. The thickness of the hepatic artery intima, which surpasses 200 microns indicates that the subject is at least 40 years of age, while initial atherosclerosis--the 8th or 9th decades of life. PMID- 11208279 TI - Genotoxicity of chromium in human gastric mucosa cells and peripheral blood lymphocytes evaluated by the single cell gel electrophoresis (comet assay). AB - Hexavalent chromium compounds are well-recognized carcinogens. They easily penetrate the cell membrane and are reduced inside the cell to their trivalent form, which is supposed to react directly with DNA. Chromium is present in some workplaces as well as in water resources and food chain, so it can interact with the mucosa of the gastrointestinal tract. In order to elucidate the genotoxic potency of chromium in human gastric mucosa (GM) cells, the DNA-damaging effect of potassium dichromate (K2Cr2O7) was investigated using alkaline single cell gel electrophoresis (comet assay). Biopsy samples were obtained during gastroscopy from macroscopically healthy tissue of the stomach. Parallel test with human peripheral blood lymphocytes was also performed. Both types of cells were incubated at 37 degrees C with 1.6 mM of K2Cr2O7 for 1 h and after washing, were placed in a chromium-free medium to examine DNA repair. Alkaline single cell gel electrophoresis (comet assay) was used to assess DNA damage and repair. Chromium introduced a damage to DNA both in the GM cells and lymphocytes. The effect induced by K2Cr2O7 in GM cells was comparable with that caused in the lymphocytes. Treated cells were able to recover within a 60-min incubation in a chromium-free medium at 37 degrees C. The results obtained indicate that hexavalent chromium compounds, which may be found in the diet, can interact directly with DNA of the mucosa of the stomach. PMID- 11208280 TI - Composition of phospholipid fatty acids in erythrocyte membranes of children with chronic juvenile arthritis: clinical and biochemical correlations. AB - Systemic diseases of connective tissue, including chronic juvenile arthritis are associated with a number of metabolic disorders such as e.g. lipid disturbances. The purpose of the present work was to analyse the composition of fatty acids in erythrocyte phospholipids of children with juvenile chronic arthritis and to determine a correlation between the composition of these acids and patients' clinical status. The study was conducted on 47 children with juvenile chronic arthritis (jca) and 29 healthy subjects. The following fractions of phospholipids were obtained with the help of thin-layer chromatography: phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidyloinositol, cardiolipin, sphingolipin. Fatty acids were analysed with the use of gas chromatograph (Hewlett-Packard 5890). Saturated fatty acids as well as mono- and polyunsaturated (n-3 and n-6) fatty acids were identified. The decrease in the percentage of linolenic acid, PUFA n-6 and PUFA n-3 was found in all the phospholipid fractions in children with jca when compared with control group. There was a concurrent increase in saturated fatty acids, mainly stearic and palmitic acids. The differences in the distribution of fatty acids in erythrocyte phospholipids were observed at early stage of the disease and they became more conspicuous as inflammatory process proceeded. PMID- 11208282 TI - Septal branches of right coronary artery as a source of blood supply to interventricular septum in morphological and clinical studies. AB - The aim of this article was to investigate septal branches of the right coronary artery in order to create both their typologies and to evaluate the usefulness of the vessels mentioned above for revascularisation procedures on the interventricular heart septum. The clinical studies were performed on 58 human hearts aged 28-80. Technical method of direct preparation, corrosive preparation and coronarographic picture assessment. The tests showed that the number of septal branches ranged from 5 to 11, their diameter from 0.7 to 1.2 mm. There were no main trunk or vessels with different dimensions than other arteries. Creation of septal vascularisation model was not possible because of rapid changes in studied vessels, their distribution and small diameters (about 1 mm) disqualifying them for direct revascularised operations on interventricular heart septum. PMID- 11208281 TI - Influence of dehydroepiandrosterone on platelet aggregation, superoxide dismutase activity and serum lipid peroxide concentrations in rabbits with induced hypercholesterolemia. AB - Special interest in the role of DHEA dates back to the finding of a correlation between low serum DHEA concentrations and a higher morbidity and mortality rate due to coronary diseases in humans. Animal studies with experimental atherosclerosis confirmed the anti-sclerotic effect of DHEA. The mechanism of DHEA action remains unclear. We determined the influence of dehydroepiandrosterone (DHEA) administration, a potential anti-atherogenic agent, on platelet aggregation, platelet superoxide dismutase (SOD) activity and serum lipid peroxide (LPO) levels in male rabbits fed on a normal and atherogenic diet. 44 adult male New Zealand white rabbits were divided into 4 groups: 1--control group fed on standard rabbit food, 2--fed on an atherogenic diet, 3--fed on an atherogenic diet with DHEA, 4--fed on standard food with DHEA. We detected blood platelet aggregation following (ADP) and collagen activation by means of photometry. Platelet SOD activity was detected by means of fluorometry determining the inhibition of adrenaline auto-oxidation. The serum LPO concentration was measured by means of the colorimetric method. The serum DHEA-S concentration was measured by means of RIA methods, and serum lipid levels were measured by means of Biomerieux manufactured kits. Results demonstrate that (1) elevated LPO concentrations in rabbits with hyperlipidemia did not decrease following DHEA administration. (2) In rabbits fed on a normal diet, DHEA caused a decrease of LPO, which emphasizes the positive influence of this steroid on the oxidative stress in healthy animals. Such a result was not seen in the group with severe hyperlipidemia. (3) Rabbits with hyperlipidemia demonstrated a significantly decreased SOD activity. (4) In healthy animals as well as in those with hyperlipidemia, DHEA administration caused an increase of platelet SOD activity, the main enzyme of the antioxidant defence system, which protects the organism against free radical damage (5) (DHEA had no influence on platelets aggregation in both tested groups). IN CONCLUSION: DHEA administration improves platelet SOD activity, which protects cells against oxidative damage. The hypothesis that DHEA administration leads to an increase in antioxidant potency requires further investigations. PMID- 11208283 TI - Cerebrospinal meningitis with the presence of Acinetobacter spp. AB - The study was conducted on 16 strains of Acinetobacter sp. which were isolated from cerebrospinal fluid. The diagnostic material was analysed with the use of automatic BacT/Alert system (Organon Teknika). The analysis was performed in the Department of Microbiology, Medical University in Bydgoszcz. API 20NE system (bioMerieux) enabled the identification of 14 strains (87.5%) as A. baumannii, 1 strain as A. haemolyticus and 1 strain as A. lwoffii. The micro-organisms were isolated from patients whose age ranged between 4 and 66 years. These patients were treated in the departments of Neurosurgery (75.0%), Neurology (18.8%) and Intensive Therapy (6.2%). The infection of cerebrospinal fluid was caused by injury and subsequent exposure to the bacteria present in external environment. Antibiotic-sensitivity of these micro-organisms was evaluated with the help of disc-diffusion method, observing standardisation conditions outlined by NCCLS. All the strains proved sensitive to carbapenems, 15 strains were sensitive to netilmicin, 7 strains--to tobramycin and 7 strains--to amikacin. All the strains displayed multiple resistance. The only exception was A. haemolyticus. The use of two-discs allowed for the detection of ESBLs in 7 A. baumannii strains. Positive results were most frequently obtained after the combination of sublactam and aztreonam. Due to microscopic resemblance between Acinetobacter spp., and bacteria of Neisseria, Moraxella and Haemophilus genus, microbiological diagnostics should not be restricted to microscopic assessment of cerebrospinal fluid and quick serological tests evaluating the antigens of the most frequent aetiological factors. Considering multiple resistance of Acinetobacter spp. to antibiotics, the treatment should be based on sensitivity tests and the ability of a given antibiotic to penetrate into cerebrospinal fluid. In our opinion, both reasonable antibiotic policy as well as observing the principles of hygiene and monitoring infections play equally important roles in the prevention of infections with Acinetobacter spp. Such combined measures may help to prevent the spreading of multiple resistant strains in hospital environment. PMID- 11208284 TI - Gas exchange and heart rate kinetics during binary sequence exercise in cystic fibrosis. AB - MATERIAL AND METHODS: Gas exchange and heart rate (HR) kinetics were investigated in 20 patients with cystic fibrosis (CF) by using a pseudorandom binary sequence (PRBS)-technique. Electrocardiogram was continuously recorded, and VO2, VCO2 and ventilation/min (VE) responses to a multifrequent input signal were measured by means of breath-by-breath analysis. Lag time and peak value in the time-domain, and amplitude ratios in the frequency-domain were calculated to characterize the crosscorrelation functions between input and responses, and compared to normal ranges. RESULTS: Time and frequency domain parameters are abnormal for VO2, VCO2 and VE responses in moderately and severely ill patients, and for the HR response only in severely ill patients. Correlations are shown between those parameters, the severity of the illness evaluated by the Shwachman score and the level of impairment of the pulmonary function. CONCLUSION: The PRBS-technique is a useful tool to investigate the gas exchange and HR kinetics in CF patients, that offers many advantages: (1) no explicit mathematical models are assumed, (2) it is a walking test that may be used even in very young or severely ill patients, and (3) it challenges the ability to adapt to non-steady state exercise and is therefore representative for daily activities. PMID- 11208286 TI - Non-Hodgkin's lymphomas with primary localization in large bowel and rectum. AB - From 1989, at the Department of Medical Oncology of the Institute for Oncology and Radiology in Belgrade, seven patients with primary NHL of large bowel and rectum have been observed and treated, 3 males and 4 females. In 3 patients an urgent laparotomy without previous diagnostic procedures was performed, while 4 patients had laparotomy only after radiographic and endoscopic diagnosis of a tumor. Six patients had radical surgery and 1 palliative only. Five patients had lymphoma localized in cecoascedental part of colon (2 centroblastic, 1 lymphoplasmocytic, 1 Burkitt and 1 Burkitt's like), 1 patient had it in the transversal part of colon (centroblastic), and one in the rectum (diffuse centrocytic). By further investigation, in 2 cases with localization within transversal part of colon and rectum no other sites of NHL were found. They are under regular controls with 45+ and 45+ months disease free survival. Out of 5 patients with localization within cecum or ascendent part of colon, in 2 cases with Burkitt/Burkitt-like histology retroperitoneal lymphadenopathy were found, one female had NHL central propagation, and the other one lymphoma generalization. Both patients had early death from lymphoma. The remaining three patients following chemotherapy with the ProMACE regimen (as they too had a post laparotomy stage II disease) achieved a complete response lasting for 36+, 41+ and 66+ months. Since the median survival in our group of patients is at the moment 41+ months and the median has not yet been reached, our experience does not confirm literature data claiming bad prognosis of primary NHL of the colon and rectum. A long disease free survival can be obtained in these patients either with surgery only or surgery + chemotherapy, depending on disease stage and possibly initial topographic localization. PMID- 11208285 TI - Pretreatment determination of isohaemagglutinin titter values in patients with malignant lymphomas and metastatic solid tumors. AB - Isohaemagglutinin synthesis starts 2-4 months after birth, growing progressively and reaching adult values at the age of 5-10 years. Isohaemagglutinin concentration decreases with age. Isohaemagglutinins are mostly immunoglobulins belonging to the class IgM, but also IgA and IgG. Agglutination titter shows correlation with the total concentration of those three immunoglobulin isotypes. For the time being there are few data on the isohaemagglutinin titter level in various diseases. Purpose of this work is to determine whether there are any isohaemagglutinin titter alterations in patients with neoplasia. Isohaemagglutinin titter was investigated in 177 patients treated at the Institute of Oncology and Radiology and 340 blood donors. Out of 177 patients, 31 had Hodgkin's lymphoma (HL), 89 had non-Hodgkin Lymphoma (NHL) and 57 had metastatic solid tumors (MST). Statistical evaluation included Kruskal-Wallis and Mann-Whitney tests. In all groups of patients isohaemagglutinin titters were considerably lower as compared with the healthy population (p < 1 x 10e-5). There was a significant difference in titter values (p = 0.003) between O blood group patients with NHL where anti-A1 titter was significantly lower (Med = 8; range: 1 256) compared with anti-A1 titter in patients with O blood group suffering from MST (Med = 16; range: 2-64). Anti-B titter in the same groups of patients also showed lower values (p = 0.042); in NHL anti-B titter values was Med = 4, range: 1-32 vs Med = 8, range: 1-64 in MST. In the group of patients with HL, A blood group was far more frequent (17/31) compared with the group with MST (22/57) (p = 0.02). Pretherapy determination of isohaemagglutinin titter in patients with malignant diseases shows that it is significantly lower than the titter in healthy population. Abnormally low isohaemagglutinin titter value irrespective of the type and site of the malignant tumor, points to insufficiency of the IgM related humoral immune response, to malignancy as a systemic disease, and places isohaemagglutinins among biological markers. PMID- 11208287 TI - Early predictors of 30-day mortality in supratentorial ischemic stroke patients- first episode. AB - INTRODUCTION: Prognostic factors following stroke remain to be established. The aim of this study was to determine early prognostic factors related with a 30-day mortality in first episode ischemic stroke patients. MATERIALS AND METHODS: The study group comprised 329 consecutive patients, aged between 33 and 99 years (mean age +/- SD 69 +/- 12.6) admitted within 24 hours following their first supratentorial ischemic stroke, confirmed either by computer tomography (CT) and/or autopsy. The following data were assessed within 24 hours of hospitalization: gender, age, history of diabetes mellitus, history of ischemic heart disease, obesity, the neurological deficit at entry and after one day, level of consciousness at entry and after one day, electrocardiographic dysrhythmia at entry, blood pressure at entry and body temperature on the first day following stroke. We also assessed particular serum biochemical and hematological markers including: hematocrit, fibrinogen concentration, platelet count, white blood cell (WBC) count, gamma globulin level, glucose level, cholesterol level, the erythrocyte sedimentation rate (ESR), and creatinine kinase (CK) level. The end-point for assessment was early death (within 30 days). Statistical analysis consisted of univariate analysis and multiple regression. RESULTS: Univariate analysis demonstrated that an older age, increased neurological deficit at entry and on the next day, decreased consciousness at entry and on the next day, electrocardiographic dysrhythmia, increased body temperature and glucose level, decreased cholesterol level and increased CK level were significantly associated with death after 30 days (p < or = 0.05). During multivariate analysis, only a severe neurological deficit (Scandinavian Stroke Scale < or = 15 points) both at entry and on the next day (OR = 8.3; 95% CI: 2.83 24.35), decreased consciousness within the first 24 hours of hospitalization (OR = 19.2; 95% CI: 2.84-127.77) and electrocardiographic dysrhythmia (OR = 5.2; 95% CI: 2.37-13.77) were associated with death after 30 days. CONCLUSION: A severe neurological deficit lasting 24 hours, decreased consciousness within 24 hours of hospitalization and electrocardiographic dysrhythmia are the most important indicators of 30-day mortality in patients with first-time ischemic stroke. PMID- 11208288 TI - Rhinospirography in evaluation of respiratory disorders in patients with central nervous system tumors. AB - The aim of the study was to define respiratory disorders caused by central nervous system tumors. We investigated 51 patients (31 men, 20 women, mean age 58). They were divided into the following groups: patients with supra-, infratentorial and cranio-vertebral junction lesions. We analyzed: the localization of tumors based on CT and MRI examinations and intraoperative observation, the status of consciousness by GCS scale, neurological status and histological findings. For the estimation of dynamics of the respiratory changes, rhinospirography examination was repeated several times in the course of observation. The alterations of respiration were clearly visible in many cases. We have confirmed that respiratory disorders found by rhinospirography provide a source of important clinical information on the effect of the treatment and prognosis. We have also confirmed that changes in respiration are observed earlier than changes of consciousness. PMID- 11208289 TI - Pattern of drug use amongst antenatal patients in Benin City, Nigeria. AB - BACKGROUND: Drugs taken by pregnant women could have profound effect on pregnancy outcome for both the mother and fetus. In most developing country regulation of drug is poor, access is unrestricted and abuse of drugs especially antibiotics is rampant. The study was undertaken to determine the pattern and extent of drug consumption amongst pregnant women in Benin City. METHODS: A cross-sectional study of 1200 pregnant patients at various gestational ages was undertaken, using a structured questionnaire to obtain details of the extent and character of drug use before or during pregnancy. FINDINGS: Folic acid was taken by 76.08% of all the pregnant patients, while anti-malarial drugs were taken by 19.75%; 15.83% used the drugs on doctors' prescription and 3.92% without a doctor's prescription. The proportion of the mothers that consumed native herbs was 12.08%. The use of native medication was more prevalent amongst nulliparous mothers (41.82%). Native herb consumption decreased with increase in parity. Both educated and illiterate mothers consumed herbal medications. Less than 1% of the mothers smoke cigarettes. INTERPRETATION: In Benin City drug use in pregnancy is characterized by a pattern of low consumption except folic acid and native herbs. This could be a major setback for any program of drug intervention, as in chemoprophylaxis for malaria in pregnancy. Much resource will be needed for patients' education for successful implementation of any planned program in the community. PMID- 11208290 TI - Total intravenous anaesthesia with methohexitone or propofol for knee arthroscopy in day-case surgery. AB - The aim of the study was to assess the usefulness of methohexitone and propofol in total intravenous anaesthesia applied during planned knee joint arthroscopy in day-case surgery. Studies comprised 186 patients divided into 2 groups depending on the anaesthetic used (methohexitone n = 112 or propofol n = 74). ECG, heart rate, systolic and diastolic blood pressure and blood saturation using pulsoxymetry were monitored during anaesthesia. The time of regaining consciousness was measured and the orientation test was performed 5 and 10 minutes after regaining consciousness. Our results and observations confirm that total intravenous anaesthesia is useful in day-case surgery for knee joint arthroscopy. Both methohexitone and propofol cause cardiac and respiratory depression. Patients on propofol regain psychomotoric efficiency earlier then patients who received methohexitone. PMID- 11208291 TI - Particular fractions of microproteinuria in patients with stabile angina pectoris and without a clinical nephropathy. AB - The determination of microalbuminuria is a valuable method in the diagnosis of renal and vascular diabetes or hypertension complications. Recently, microalbuminuria appeared to be the predictor of coronary heart diseases (CHD). The presented study comprised 26 patients with stable angina pectoris (AP) and 27 healthy volunteers. We simultaneously evaluated microproteinuria during the first morning and afternoon miction and the 24-h blood pressure. Amongst patients with AP all urine protein concentrations were increased (results in g/mol creatinine): alpha-1-microglobulin (1.04 + 0.13 vs. 0.47 + 0.05, p < 0.001) albumin (0.95 + 0.15 vs. 0.61 + 0.05, p < 0.05) and IgG (1.00 + 0.17 vs. 0.55 + 0.05, p < 0.01) were higher, in comparison to control group values. Indices for diurnal blood pressure rhythm were significantly lower in the AP group for both systolic (1.07 + 0.01 vs. 1.14 + 0.01 p < 0.001) and diastolic (1.09 + 0.02; vs. 1.21 + 0.03 p < 0.01) pressures. A physiological increase of albumin from the afternoon sample was only observed in the control group. Thus, our AP patients demonstrated signs of subclinical nephropathy in both the proximal tubuli and glomeruli. PMID- 11208292 TI - Ultrasound picture of gastroesophageal junction in children with reflux disease. AB - The assessment of gastroesophageal junction morphology is very important in children with reflux disease. Authors present ultrasonographic measurements of subdiaphragmatic part of the esophagus and His angle. In children with reflux disease, marked shortening of subdiaphragmatic part of esophagus and completely obtuse His angle were found. Ultrasound imaging of gastroesophageal junction is valuable part of ultrasound diagnostics of reflux and may be helpful in establishing the etiology and choosing the treatment method. PMID- 11208293 TI - QT interval duration in 24-hour Holter monitoring after different interventional treatment of coronary artery disease in patients after the myocardial infarction. AB - QT interval prolongation is discussed as a possible risk factor of dangerous arrhythmias. The aim of this study was to evaluate the influence of different interventional treatment of coronary artery disease in patients after myocardial infarction on QT interval duration. Two groups of patients were analyzed. The first group (G1) consisted of 37 patients in whom PTCA was performed; the second group (G2)--42 pts after surgical myocardial revascularisation (CABG). The 24 hour electrocardiography monitoring was performed in all the patients. Results were analyzed especially considering the average daily values of QT, QTp, QTc and RR duration. In patients after CABG we observed statistically significant prolongation of QTc interval duration what was not noticeable in patients after PTCA. The cardiosurgical procedure of coronary by-pass grafting in patients with coronary artery disease after the myocardial infarction in contrary of PTCA may lead to significant prolongation of QTc interval duration. This problem needs further investigation. PMID- 11208294 TI - Fibrinolysis system in patients with bronchial asthma. AB - Every inflammatory process, including that in the course of bronchial asthma may disturb the balance in blood coagulation and fibrinolysis system. The aim of the present study was to evaluate fibrinolysis in patients with bronchial asthma. The study group consisted of 41 patients with bronchial asthma, hitherto untreated (25 women, 16 men, at mean age 37.37 +/- 12.4 years) and 22 healthy adults (control group). In these subjects, the following parameters were established: euglobulin lysis time (ELT), the concentration of tissue plasminogen activator antigen (t-PA Ag), the concentration of urokinase plasminogen activator antigen (u-PA Ag), the activity of plasminogen activator inhibitor type 1 (PAI-1), the concentration of plasmin-antiplasmin complex (PAP) and fibrinogen/fibrin degradation products (FDP). It was found that patients with bronchial asthma had statistically significantly higher mean values of FDP (9.25 +/- 6.7 micrograms/ml vs. 5.0 +/- 5.9 micrograms/ml; p < 0.001), ELT (123.5 +/- 42.7 min vs. 97.4 +/- 27.1 min; p < 0.001), t-PA Ag (8.36 +/- 3.66 ng/ml vs. 5.5 +/- 3.71 ng/ml; p < 0.01) and PAP complexes (250.3 +/- 95.8 ng/ml vs. 193.4 +/- 60.7 ng/ml; p < 0.02). Mean u-PA Ag concentration in patients with bronchial asthma was significantly lower than in control group (0.24 +/- 0.16 ng/ml vs. 0.53 +/- 0.18 ng/ml; p < 0.01). No statistically significant differences were observed as to PAI-1 activity between patients with bronchial asthma and healthy subjects. The results of the present study suggest that increased concentrations of t-PA Ag, PAP and FDP complexes are the evidence for greater activity of fibrinolysis system in subjects with bronchial asthma. PMID- 11208295 TI - Children with acute lymphoblastic leukemia: is there any subgroup of children without elevated thrombin generation? A preliminary study utilizing measurements of thrombin-antithrombin III complexes. AB - The mechanisms contributing to thromboembolic complications in children with acute lymphoblastic leukemia (ALL) are complex, but it is believed that two factors are of critical importance, i.e. increased thrombin generation and decreased antithrombotic potential of the blood plasma. We evaluated generation of thrombin in three periods of observation of the children: a) prior to chemotherapy, b) after remission-inducing chemotherapy, and c) after infusion of L-asparaginase in the consolidation phase. The study group consisted of 23 children (x = 6.8 years of age), and a control group of 11 children (x = 7.3 years of age). Thrombin-antithrombin III complex (TAT) was selected as a marker of thrombin generation and it was measured by ELISA method. TAT levels prior to chemotherapy were found to be normal in a small subgroup of children (7/23--ca 30%), i.e. they were within the control range (1.5-4.5 micrograms/l), but all the levels increased following remission-inducing chemotherapy. In contrast, in the major subgroup of children whose TAT levels were elevated at presentation (16/23- ca 70%) no significant changes were observed following chemotherapy. CONCLUSION: There is a subgroup of children with ALL whose thrombin generation is normal as measured by its marker--thrombin-antithrombin III (TAT). Only in those children thrombin generation increases following chemotherapy. PMID- 11208296 TI - Enzymatic efficiency of erythrocyte antioxidant barrier and lipid peroxidation in children from families with high risk of early atherosclerosis. AB - The most important risk factors contributing to the development of atherosclerosis include lipid disorders and the predisposition to early ischaemic heart disease in the family. Atherosclerotic process proceeds with age and it develops as a result of oxide LDL modification at the level of vascular wall. Oxygen-free radicals take part in this process, which may probably be opposed by the antioxidant system of the body. The aim of this study was to compare the intensity of lipid peroxidation and the activity of antioxidant enzymes in children from the families with the risk of early atherosclerosis and in children without such predisposition. The activity of katalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined and the concentration of malonic dialdehyde--a lipid peroxidation marker was established. The study was conducted on 76 children aged 4-17 years, mean age 12 +/- 0.6 years. The risk group consisted of 56 patients with the history of hypercholesterolaemia and early atherosclerosis in the members of their families up to 45 years of age. Control group was formed of 20 subjects without such history. MDA concentration as well as the activity of antioxidant enzymes were determined with the use of adequate methods of spectrophotometry. The results obtained were subject to statistical analysis. The activity of antioxidant enzymes displayed considerable fluctuations in both groups of children, but these differences remained statistically insignificant in all the cases. Higher MDA concentrations in serum and in erythrocytes were observed in the risk group. These differences proved statistically significant (alpha < 0.05). On the basis of the present study and the analysis performed, it was found that the activity of antioxidant enzymes (CAT, SOD, GSH-Px) cannot serve as a parameter differentiating between children from the families with the risk of early atherosclerosis and children without such predisposition. Children with positive family history of hypercholesterolaemia and early atherosclerosis may demonstrate intensive lipid peroxidation, but this hypothesis requires further investigations. PMID- 11208297 TI - Epidemiological and clinical characteristics of rotaviral diarrhoea in children from Gdansk, Gdynia and Sopot. AB - The aim of the present work was to analyse clinical picture of rotaviral diarrhoea and its incidence in children from Tri-city. The study was conducted on 773 children aged 1 month-11 years, who were treated in selected hospitals in 1997 due to acute diarrhoea. Apart from physical examination and collecting patients' medical history, each child was subjected to routine laboratory investigations in accordance with clinical indications. Rotaviral aetiology of the infection was confirmed in 275 out of 773 patients with acute diarrhoea. In 80.7% cases, the disease affected children aged 7-36 months old and it was more frequent in boys than in girls. Acute diarrhoea was diagnosed mainly during cold months of the year, and the increase of its incidence was recorded between March and May. The duration of the disease usually did not exceed 3 days and its symptoms included fever, vomiting and dehydration which normally required parenteral administration of fluids. Statistical analysis was performed in order to estimate the differences in the incidence and intensity of the symptoms of rotaviral and bacterial diarrhoea. The present study showed that clinical picture of rotaviral diarrhoea in children from Tri-city was similar to that reported in literature on the subject, but there were differences regarding the seasonal occurrence of the infection which was probably related to the climate of analysed region. PMID- 11208298 TI - Soluble HLA class I antigens in serum of healthy individuals--population study. AB - Variability of concentrations of s-HLA-I depending on allelic specificity substantiated realisation of research in population of 248 healthy, unrelated individuals. Defined phenotypes from tissue typing of polymorphic HLA complex enabled concentrations measurements of 1553 serum samples for HLA--A, B, and C loci determined antigens. Semi-quantitative technique of inhibition microcytotoxic reaction according to Tait et al. (1981) and Mclean et al. (1983) with usage of policlonal sera anti-HLA was applied. For most of numbers of the allelic specificity the concentration of antigen material in soluble form (s-HLA I) in blood serum were nominally very high and high. For certain numbers of specificity e.g. HLA--A26, A29, B39, B52, B56, Cw5, Cw6 the percentage of sera, where the s-HLA concentrations were decreased was observed. The results were presented as mean values of inhibition microcytotoxic reaction--according to NIH classification. Authors point on usefulness of results for s-HLA comparative analysis of particular HLA allelic specificity, specific for certain diseases e.g. Cw7 for SNHL patients and B27 for ankylosing spongilitis. PMID- 11208299 TI - Self-care of young diabetics in practice. AB - To determine whether young diabetics follow the most important rules of diabetes educational programs as remembering to carry 'soluble sugars' and insulin shots in their daily life, the analysis using 263 simple and anonymous questionnaires was performed. The study involved 183 IDDM children from Kansas-USA (76 boys, 107 girls) and 80 IDDM children from Silesia, Poland (36 boys, 44 girls) of mean age 12.95 +/- 2.65, mean IDDM duration 4.77 +/- 3.15 years, mean HbA1c 8.53 +/- 1.93%. We found: (1) 79.85% of all IDDM children carry something to treat or prevent hypoglycemia, more girls than boys, and more American than Polish ones (p < 0.01). (2) Only 59.92% of IDDM children carry 'soluble sugars' (no statistically significant differences between sexes and nationalities). (3) No correlation between carrying 'sugars' and age, metabolic control, number of glycemia measurements, forgetting insulin injections and kind of insulin therapy. (4) Duration of diabetes was not correlated with carrying 'sugars' whereas it was correlated with carrying 'other food' (p < 0.05). (5) 53.4% of children never forget insulin injections (p < 0.01). (6) Forgetting insulin shots was correlated with IDDM duration in boys group, with increasing level of HbA1c and with smaller number of glycemia measurements in all children groups, with the intensive insulin therapy in girls and Polish groups (p < 0.01 in all cases). CONCLUSIONS: 1). Diabetic children quite often carry nothing or 'non-soluble sugars' with themselves to treat hypoglycemia. 2). Diabetic children more often forget to shoot insulin injections than to 'carry sugars'. 3). Children with a longer duration of diabetes more often forget their insulin injections. 4). Older girls with longer duration of IDDM demonstrating worse metabolic control check their glycemia less frequently and more often forget the insulin injections. PMID- 11208300 TI - Incidence of anorectal malformations in Lodz province. AB - PURPOSE: It is difficult to obtain reliable figures on incidence of anorectal malformations (ARM) from literature. The aim of the present study was to reveal the real incidence of these defects in a given area. MATERIAL AND METHODS: Between 1992 and 1997, 86 children with ARM were treated at the departments of paediatric surgery in Lodz. Parents of 30 (34.9%) children treated within the analysed period lived in the Lodz province. The real incidence of ARM in this area was calculated and birth parameters of children with ARM were compared with corresponding parameters of newborns born alive in Lodz. RESULTS: The studied incidence ranged from 1 in 1446 to 1 in 3035 in consecutive years and the average was 1 in 2295. Mean duration of pregnancy in children with low type ARM was 39.4 weeks and in children with high type ARM--38.8 weeks. Mean birth body weight of children with low defects was 3030 g, and of neonates with high defects--3185 g. Apgar score was respectively 8.7 and 8.8. There was also no significant difference in examined parameters (p > 0.05) between ARM children and the population of born alive newborns of Lodz area (respectively 38.9; 3297; 8.9). CONCLUSIONS: Anorectal malformations are among the common congenital anomalies in children. In the analysed group of children with ARM duration of pregnancy, birth weight and Apgar score were similar to these observed in the whole population of newborns born alive in Lodz province. PMID- 11208301 TI - Perioperative management of a post heart transplantation patient with renal failure qualified to lung resection. AB - Since the first heart transplantation (1967, Christian Bernard), hundreds of similar procedures have been performed all over the world. Considerable advance made in immunosuppressive treatment improved survival rate and long-term efficiency of treatment improved survival rate and long-term efficiency of treatment. Many of these patients suffer from ailments requiring operations which are not connected with the transplanted organ. The present study describes a case of a post heart transplantation patient qualified to lung resection, in whom renal insufficiency occurred in the course of immunosuppressive therapy. PMID- 11208302 TI - 8q22-->qter duplication in a child with multiple congenital malformations: case report. AB - BACKGROUND: Congenital malformation syndromes are often caused by unbalanced chromosome translocations, which appear spontaneously or may be inherited from a healthy parent being the carrier of a balanced reciprocal translocation (rcp). Breakpoints, underlying chromosome fragment exchanges, may be located at any point of any chromosome and therefore, an infinite number of different translocations is possible. Special emphasis is placed both on the clinical characterization of every rare chromosomal aberration syndrome and on the determination of its breakpoints. OBJECTIVES: Diagnosis of a 8q22-->qter duplication in a child with multiple congenital malformations. MATERIAL AND METHODS: We determined the karyotypes of the five members of proband's family were established by using classical cytogenetic methods on whole blood obtained by venipuncture. RESULTS: We described a rare familial reciprocal translocation t(8; 14), observed in balanced form in mother and one healthy son, while being unbalanced in the son with congenital malformations. CONCLUSIONS: Balanced chromosome 8 aberration carriers should be aware of the procreation risks and need genetic counseling. PMID- 11208303 TI - Idiopathic hypoparathyroidism with intracranial calcifications and dominant skin manifestations. AB - Presented here is an unusual case of a 41-year-old man with idiopathic hypoparathyroidism strongly connected with dermatological, ophthalmological and neurological disorders. Since the age of 4 he had been treated ineffectively for mycosis resulting in complete baldness and atrophic nail plate changes. At the age of 35 he was diagnosed with idiopathic hypoparathyroidism. He underwent surgery twice due to bilateral cataract. CT scans of the head demonstrated numerous symmetrically located calcifications in both frontal lobes, subcortical nuclei, the paraventricular region, brain fornix, and both cerebellar hemispheres. The neuropsychological examination demonstrated the occurrence of psychosensory disorders under the form of hallucinations accompanied by a sense of fear and anxiety. It seems essential to investigate the parathyroid gland for any sign of pathology, especially amongst patients with severe dermatological and/or neuropsychological symptoms. Early diagnosis and treatment of patients with hypoparathyroidism may prevent the development of many serious complications or at least result in marked improvement of neurological manifestations. PMID- 11208304 TI - Wegener's granulomatosis--clinical analysis of 18 patients group. AB - In observed, during 15 years group, of 18 patients with established Wegener's granulomatosis WG diagnosis, important is period of time from onset of the manifestations to WG diagnosis--very diversified, between 3 to 96 months and heterogenerosity of clinical manifestations during establishing of the diagnosis. Separated from clinical and histopathological features in most of the patients the presence of the titre of antineutrophil cytoplasmic antibody (ANCA) in blood serum examinations was established--75% among 16 observed patients in whom such examination was possible to perform. There was no significant correlation between ANCA titre and prognosis of the WG course. Most of the patients developed upper respiratory tract, ears, lungs and kidney disease involvement. Cyclophosphamide (CF) and prednisolone (P) treatment improves clinical remission in most of the patients (88.8%) and possibility of the course of the disease control. However often recurrences are observed (50%) and side effects due to the long term CF and P treatment (60%). 38.8% of patients achieve long term remission of the manifestations. 3 deaths of WG patients were observed during that period. Patients require during treatment close collaboration and careful periodical control of treatment. PMID- 11208305 TI - Biomechanics of soft tissues. AB - Recent developments in Computer-Integrated and Robot-Aided Surgery (in particular, the emergence of automatic surgical tools and robots (as well as advances in Virtual Reality techniques, call for closer examination of the mechanical properties of very soft tissues (such as brain, liver, kidney, etc.). Moreover, internal organs are very susceptible to trauma. In order to protect them properly against car crash and other impact consequences we need to be able to predict the organ deformation. Such prediction can be achieved by proper mathematical modelling followed by a computer simulation. The ultimate goal of our research into the biomechanics of these tissues is development of corresponding, realistic mathematical models. This paper contains experimental results of in vitro, uniaxial, unconfined compression of swine brain tissue obtained by the author in Mechanical Engineering Laboratory, Japan, and discusses liver and kidney in vivo compression experiments conducted in Highway Safety Research Institute and the Medical Centre of The University of Michigan. The stress-strain curves for investigated tissues are concave upward for all compression rates containing no linear portion from which a meaningful elastic modulus might be determined. The tissue response stiffened as the loading speed increased, indicating a strong stress (strain rate dependence. As the step in the direction towards realistic computer simulation of injuries and surgical procedures, this paper presents two mathematical representations of brain, liver and kidney tissue stiffness. Biphasic and single-phase models are discussed. The biphasic model is shown to be inappropriate due to its inability to account for strong stress-strain relationship. Agreement between the proposed single-phase models and experiment is good for compression levels reaching 30% and for loading velocities varying over five orders of magnitude. Presented mathematical models can find applications in computer and robot assisted surgery, e.g. the realistic simulation of surgical procedures (including virtual reality), control systems of surgical robots, and non-rigid registration, as well as ergonomic design for injury prevention. PMID- 11208306 TI - New formula for calculating antibiotic critical concentration by the disk diffusion method. AB - New formula was designed for calculation of the antibiotic critical concentration: Cc = (1/pi Bh)e-A/B where h is agar depth, B is the slope, A is the intercept. The formula is derived from the second Fick's law. Neither diffusion constant nor critical time data apply. Three or more disks containing varied concentrations of the same antibiotic are used. Regression analysis of square of zone of inhibition radii is performed and subsequently the critical concentration is computed. PMID- 11208307 TI - Principles in laboratory animal research for experimental purposes. AB - The present work contains information about proper husbandry and care of laboratory animals, microbiological monitoring of their health and protecting them against suffering and distress. The author also gives some advice on the improvement and unification of experimental research results through the standardisation of laboratory animals used for the experiments as well as imposing proper conditions for animal husbandry. PMID- 11208308 TI - Diagnosis and treatment of primary biliary cirrhosis. AB - Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease that predominantly occurs in middle-aged women of various ethnic and racial populations. The disease slowly progresses over decades and is supposed to be caused by immune reactions against host antigens. Histologically, it is characterized by inflammatory destruction of intrahepatic small bile ducts, subsequent fibrosis, and finally liver cirrhosis. It is more frequently diagnosed now than in the past probably because of a greater awareness of the disease. There is only week association of PBC with genetic markers. Liver function tests reveal an elevation of serum alkaline phosphatase and gamma-glutamyl transpeptidase levels with or without elevated aminotransferase levels. The hallmark of the disease is the presence of antimitochondrial antibodies (AMAs), which are found in 95% of patients with PBC. AMAs have been shown to be directed against the 2-oxo-acid dehydrogenase complexes located on the inner membrane of the mitochondria. However, AMA titers do not correlate with the disease severity of progression, and the role of AMAs in the pathogenesis of PBC has not been shown. The disease is frequently associated with other autoimmune diseases, including Sjogren's syndrome, scleroderma and thyroid disorders. Most therapeutic efforts have been directed at altering the immune response. Ursodeoxycholic acid (UDCA) appears to be effective therapy in preventing or delaying the need for liver transplantation and improving survival. However, a number of patients receiving UDCA still develop progressive disease and go on to transplantation, which is an effective therapy at the end stage of the disease. Various prognostic models have been proposed to estimate the survival probability and assist in the determination of the optimum timing of liver transplantation. PMID- 11208309 TI - Use of local anaesthetic agents among New Zealand plastic surgeons--their practices and philosophies. AB - PURPOSE: Skin lesions are treated by a variety of medical practitioners. To describe the method and techniques of use of local anaesthetic (LA) for excision of skin lesions amongst a group of surgeons who are frequent users. METHODS: An open-ended questionnaire was designed to investigate the way LA was used for local excision and reasons behind the practice. All registered Plastic and Reconstructive Surgeons in New Zealand were sent the questionnaire. This group was chosen because they are high frequency users of local anaesthetic for excision of skin lesions. RESULTS: Questionnaires were sent to all 28 Plastic and Reconstructive Surgeons in New Zealand of which twenty-three (82%) responded. The reasons for selection of specific products relate to convenience of product (14), speed of onset (6), effect duration (4), ease to add bicarbonate (3), others (5). Lignocaine and bupivicaine were the most popular LA agent used except when there was concern about cardiac toxicity when Prilocaine was used instead. Adrenaline was used for vasoconstriction induced haemostasis, and avoided in anatomical areas with end arteries due to the risk of tissue ischaemia. This complication was identified as medicolegally indefensible despite a lack of scientific evidence in the literature. The techniques used to reduce patient discomfort of local anaesthetic infiltration relate to patient oriented techniques (15), injection related techniques (25), LA agent related techniques (19). Details of these specific techniques are presented in detail. CONCLUSIONS: LA uses vary according to the specific surgical situation, patient risk factors and according to the individual surgeon. The main reason for selection of a specific LA agent relates to convenience and not pharmacokinetics. Injection related techniques are the most common method to reduce pain from LA. PMID- 11208310 TI - Current knowledge on treatment of chronic hepatitis B in children. AB - So far the treatment of chronic hepatitis B has been based on the use of numerous agents, particularly interferon alpha which proved the most effective. Attempts are made to introduce new therapeutic methods (antiviral agents--nucleoside analogues, immunotherapy--anti HBV vaccine, gene therapy) in order to obtain higher percentage of patients with durable inhibition of HBV replication than it is observed after treatment with interferon alpha. The current work has been devoted to the presentation of the experiences with interferon alpha, lamivudine and anti HBV vaccine used in subjects with chronic type B hepatitis, with special reference to paediatric patients. PMID- 11208311 TI - Erythromelalgia--a thrombotic complication in chronic myeloproliferative disorders. AB - Erythromelalgia is a very specific, thrombotic syndrome related with thrombocythemia that may occur during the course of chronic myeloproliferative disorders (MPD), especially polycythemia vera (PV) and essential thrombocythemia (ET). This poorly understood clinical syndrome is characterized by red, congested distal extremities and painful burning sensations, usually confined to the ball of the foot and one or more toes or fingers. If left untreated, it may progress towards acrocyanosis and even peripheral gangrene. Sometimes, it may precede the diagnosis of MPD by months or years. The pathophysiological aspects of erythromelalgia as well as its differentiation with erythermalgia have been reviewed in this study. PMID- 11208312 TI - Fatty liver--current look at the old disease. AB - The report is devoted to the presentation of aetiological factors causing fatty liver, including alcohol, obesity, diabetes mellitus, hyperlipoproteinaemias and drugs. The author discusses morphological changes typical for the fatty liver such as large or small fatty droplets in hepatocytes and rarely coexisting hepatitis (so-called steatohepatitis). The work presents symptoms, changes in biochemical analyses of serum as well as methods of the liver visualisation used in the diagnostics of fatty liver. The treatment in based on the elimination of aetiological factors and properly balanced diet with support of pharmacotherapy in selected cases. PMID- 11208313 TI - Strategy for prenatal diagnosis of osteogenesis imperfecta by linkage analysis to the type I collagen loci COL1A1 and COL1A2. AB - To improve prenatal diagnosis of osteogenesis imperfecta (OI) in Lithuania, possibilities of indirect molecular genetic diagnosis were investigated in 11 families with dominant OI. Segregation of polymorphic DNA markers closely linked to COL1A1 and COL1A2 genes with OI phenotype was investigated. Polymorphic DNA markers applied were individual haplotypes constructed using a set of restriction enzyme sites within or close to the genes. Comparison of phenotypic features with the concordant collagen locus showed that in four pedigrees with OI Sillence type I segregated with COL1A1, while two pedigrees with OI Sillence type I and OI type IV segregated with COL1A2. Out of six remaining pedigrees with OI Sillence type I, three were concordant at both loci, two pedigrees were discordant at the locus COL1A2 and non-informative at the locus COL1A1 and one pedigree was concordant at the locus COL1A1 and non-informative at the locus COL1A2. Informativity of DNA markers applied was also investigated in the Lithuanian OI families. The frequencies of six restriction enzyme site dimorphisms in type I collagen loci were estimated and polymorphism information content (PIC) values were calculated for each restriction site and for a combination of three sites. COL1A1 locus dimorphisms A/MspI, B/RsaI and F/MnlI, showed PIC values of 0.327, 0.191 and 0.366, respectively, giving a combined PIC of 0.656 at the locus, while COL1A2 locus dimorphisms C/EcoRI, D/MspI and E/RsaI RFLPs had PIC values of 0.357, 0.168 and 0.331, respectively, giving a combined PIC of 0.655 at the locus. PMID- 11208314 TI - Patterns of free and esterified sterol fractions of the cerebral white matter in severe and moderate experimental hypoxia. AB - Cerebral sterols were examined in Wistar strain rats, subjected 4 h, 24 h, 14 days or 2 months earlier to severe (2% oxygen) and moderate (7% oxygen) experimental hypoxia. From brains of the experimental animals myelin was isolated and examined by gas chromatography coupled with mass spectrometry (GC-MS) to separate and to identify free and esterified (following hydrolysis) cerebral sterols. In both types of hypoxia, the same compounds were identified in fractions of free and esterified sterols. Slight differences in sterol content were noted between the two experimental models, involving cholesterol, the main sterol of the myelin sheath, its smaller sterol precursors (desmosterol, lanosterol) and the less abundant sterols (beta-sitosterol, 24-ethyl-4-cholesten 3-on, cholesta-3,5-dien, cholest-4-en-3-on, 22-propyl-3 beta-hydroxy-5,24 cholestadien). Both types (severe and moderate) of hypoxia were found to induce similar alterations in patterns of cerebral sterols 24 h, 14 days and 2 months following the exposure. Quantitative differences in the sterol pattern were detected only at the very early stage (4 h) of the experiment. PMID- 11208315 TI - Antioxidant mechanisms in human peritoneal mesothelial cells (HPMC) exposed in vitro to the constituents of dialysis fluid. AB - OBJECTIVE: To assess effects of hyperosmolarity, high glucose concentration, and low pH with or without lactate sodium at the level of antioxidant mechanisms, such as the concentration of total intracellular glutathione (GSH/GSSG), the activity of catalase (CAT) and total superoxide dismutase (SOD) in mesothelial cells (MC) in vitro. METHODS: HPMC were obtained from omentum from nonuremic donors. The effect of pH (5.2-7.3) with or without sodium lactate (35 mM/L) was tested in Earle's salt after 30 min exposure, whereas the osmotic and metabolic effects of glucose, glycerol, mannitol, and amino acids were studied in a medium with 10% FCS after 4, 24, 72 and 104 h of exposure. The activity of antioxidant mechanisms was determined by spectrophotometry. RESULTS: In the cells exposed to Earle's salt pH 5.2 with lactate, the GSH/GSSG level, and CAT and SOD activity were substantially reduced. After 4 h of exposure, glycerol, glucose and mannitol increased the GSH/GSSG content in MC; after 24 h only glucose slightly increased the GSH/GSSG level. CONCLUSION: We conclude that although low pH with high lactate concentration decreased the activity of all studied antioxidant mechanisms in MC, the clinical relevance of these observations needs to be studied further. PMID- 11208316 TI - Changes in the structure and properties of corpus vitreous and the preservation of enzymatic composition of rabbit antioxidative system under the influence of sulphur hexafluoride gas. AB - PURPOSE: To evaluate clinical, physiochemical and biochemical changes in rabbit vitreous body caused by local injection of sulphur hexafluoride gas. MATERIAL AND METHODS: The volume of fluid vitreous fraction was measured with Na+, K+, Mg2+, Ca2+ levels and full proteins concentration in both vitreous fractions in 24 New Zealand rabbits at 2, 7 and 14 day after SF6 injection. The activity of superoxide dismutase, catalase and malonyl dialdehyde were used to evaluate the activity of antioxidative enzymatic system. Control group consisting of 6 New Zealand rabbits had no experimental procedures. RESULTS: In the investigated group, the fluid vitreous fraction volume was increased while gelatous one was diminished from 0.08 ml in control group to 0.32 ml in the study group (on day 14). The level of Na+, K+, Mg2+, Ca2+ in the fluid fraction was unchanged. On day 7, we noticed statistically significant increase in protein concentration in comparison with the control group and the study group on 14 day. The activity of superoxide dismutase and catalase as well as the level of malonyl dialdehyde were increased in the fluid vitreous fraction compared to the gelatous one in the control group. After the SF6 injection we did not observe any changes of superoxide dismutase and catalase activities in the gelatous part of vitreous body while in the fluid one there was statistically significant decrease in the enzymatic activity and the MDA level in the whole observation time. CONCLUSIONS: The injected sulphur hexafluoride gas caused the damage of the gelatous vitreous fraction with the increase in the fluid one. The oxygen free radicals might trigger these pathological processes. PMID- 11208317 TI - Neoplastic lesions of the human liver in relation to the activity of the cytochrome P-450 dependent monooxygenase system. AB - We studied the activity of Mixed function oxidase (MFO) in human livers affected by cancer. We determined the content of cytochrome P-450 and b5, as well as the activity of their corresponding reductases, according to generally accepted methods. Liver fragments corresponding with a) healthy tissue, b) tissue at the cancer border and, c) cancerous tissue were collected during surgery from patients with liver cancer. We noted that the developing liver cancer decreased the level of cytochrome P-450, even by a magnitude order. The activity of its corresponding reductase was higher in cancerous than in healthy tissues. Cytochrome b5 behaved in an analogous manner, although the decrease in its content was less significant. NADH-cytochrome b5 reductase activity changes were insignificant. PMID- 11208318 TI - Comparative morphology of the hepatic and coronary artery walls. Part II. The relation between the internal elastic membrane, non-atherosclerotic intimal thickening and atherosclerosis. AB - Evident difference in the occurrence of atherosclerosis between hepatic and coronary arteries justifies the search for local preconditions of this disease. In this study we compared the internal elastic membrane morphology of both arteries. It appeared to be mono- or polylinear (laminar) and continuous in the hepatic artery. This was in contrast to its fragmentation in the coronary artery since the beginning of life. Thus, the condition of the internal elastic membrane may play an important role in the development of non-atherosclerotic intimal thickening. Continuous elastica could make the migration of medial myocytes into the intima more difficult (hepatic artery). On the other hand, fragmented coronary artery elastica seems to facilitate this migration. In turn, intimal thickening is less or more advanced, respectively. PMID- 11208319 TI - Clinical and morphological studies on varieties of coronary vascularisation of diaphragmatic surface of human heart. AB - The aim of the present work was to determine vascularisation varieties of diaphragmatic heart surface which would be useful in cardiology and cardiosurgery, in particular. The methods used in the present study included morphological investigations (direct preparations) and clinical examinations (coronarography). The study was performed on posterior coronary vessels of 163 human hearts aged 28-88. Ninety-one of these heats were analysed on the basis of intra vitam angiography. Three coronary vascularisation varieties of posterior heart surface were distinguished and the criteria of their determination in selective coronarography were postulated. Both research methods revealed that the right variety of coronary vascularisation occurred most often, while left variety was the least frequent. Symmetric variety which is optimal from the point of view of myocardial haemodynamics was found in 0.25% cases. The frequency of the right and symmetric varieties observed in the studies following both methods are comparable. In the case of left variety, the interpretation of blood supply to posterior surface on the basis of coronarography is much more difficult when compared with the remaining varieties. Coronarography may often be insufficient to determine the range of vascularisation of particular coronary arteries. PMID- 11208321 TI - Umbilical and middle cerebral artery blood velocimetry: relationship with placental volume. AB - OBJECTIVE OF THE STUDY: To investigate the relationship between placental volume and the resistance of fetal arteries: umbilical and middle cerebral. MATERIAL AND METHODS: In 82 pregnant women with unaffected pregnancy between 14 and 40 weeks of gestation measurements of placental volume were made according to the parallel planimetric technique. Doppler examinations of umbilical and middle cerebral arteries were performed by means of a duplex system. RESULTS AND CONCLUSION: PI in the umbilical artery (PIUA) correlated significantly negatively with placental volume, whereas no significant correlation was found for the PI in the middle cerebral artery (PIMCA) and placental volume. Middle cerebral artery to umbilical artery PI ratio (PIMCA/PIUA ratio) showed significant positive correlation with placental volume. PIUA showed significant negative correlation with the relative volume of placenta (expressed as multiple of median for the actual gestational age) before 25 weeks of gestation and weak positive correlation with the relative volume of placenta after 25 weeks of gestation. PIMCA showed weak negative correlation with the relative volume of the placenta after 25 weeks of gestation and no correlation before 25 weeks. PIMCA/PIUA ratio showed significant positive correlation with relative placental volume before 25 weeks and significant negative correlation with relative placental volume after 25 weeks. PMID- 11208320 TI - Effects of interaction between cadmium and selenium on heart metabolism in mice: the study of RNA, protein, ANP synthesis activities and ultrastructure in mouse heart. AB - Heavy metals tend to occur in increasingly many aspects of human activities. Studies of cadmium (Cd) have revealed that it is extremely toxic in its effects. It is known that selenium (Se) may suppress deleterious effects of Cd. We investigated the effects of dietary Cd-intoxication on the incorporation of precursors of RNA, protein and ANP (atrial natriuretic peptide) granule synthesis in mouse cardiocytes and compared them with the results of Se interaction with Cd intoxication. Functional condition of the heart was evaluated on the basis of the number of ANP granules synthesized in cardiocytes of the right atrium in the mice exposed to the tested elements. The experiment was conducted on 100 male white Balby mouse during the period of three months. The animals were divided into four groups. The control group I (C) was fed a standard Murigran diet. Group II (Cd)- received 50 ppm Cd as cadmium acetate in drinking water. Group III (Se) received a standard diet supplemented with 5.0 mg Se/kg DM/24 h as acid sodium selenate. The experimental animals in group IV (Cd + Se)--were fed a diet supplemented with Cd and Se in the same amounts as the above groups. Our results revealed that after 3 months long intoxication with Cd, 3H-uridine and 3H-alanine uptakes to cardiomyocytes were decreased by 33% and 40%, respectively, and fewer ANP granules were synthesized when compared with the controls. Ultrastructure of myocytes proved slightly distorted. Se-intoxicated cardiomyocytes indicated diminished incorporation of RNA synthesis precursors by 17% and 27% in the ventricle and atrium, respectively, in comparison with the controls. Some Se induced structural changes were observed. Finally, after Se in interaction with Cd intoxication, the uptake of 3H-uridine and 3H-alanine to cardiocytes was higher and the number of ANP granules increased. The values approximated those in the controls. We concluded that: prolonged Cd intoxication disturbed intercellular metabolism by damaging ultrastructural elements and suppressing the incorporation of precursors of RNA, protein and ANP granule synthesis. Se in interaction with Cd revealed protective effects against Cd toxicity. After Cd-Se intoxication neither metabolic activity nor cardiocyte ultrastructure showed significant differences from those in the controls. PMID- 11208322 TI - Fractal analysis of placenta mature villi in healthy, smoking and non-smoking women. AB - Not all the objects created by nature can be described by means of the classical Euclidean geometry rules. New, quickly developing fractal theory can provide another instrument for describing irregular surfaces of e.g. geometric structures and objects whose development results from growth, differentiation and degeneration processes. In the present study we decided to perform fractal analysis of mature, terminal villi of placenta taken from smoking and non-smoking women, during the third trimester of pregnancy. The aim of this study was to find another morphometric parameter, independent of subjective factors, which would provide new information about the studied structure. Placentas were taken from healthy women, untreated primiparas, who did not undergo any hormonal treatment, aged 18 to 27. The material was divided into: control group--placentas from non smoking women, and two experimental groups--placentas from non-smoking up to 30 cigarettes daily and placentas from women smoking up to 30 cigarettes daily and placentas from women smoking over 30 cigarettes daily. Fractal dimension was determined by three methods: box counting, dilation and mass scaling method. Taking under consideration the results obtained in the present study it seems that fractal dimension, objectively and independently of many factors, allows to perform mathematical estimation of the parameter which is the terminal villi occurrence density within placenta. Among the applied fractal analysis methods, used for placenta terminal villi density grade estimation, the most useful seems to be the box counting method, whereas for estimating villi surface complication- the ratio--mass scaling method. Comparing obtained fractal dimension results, we have found that they increase together with the amount of cigarettes smoked during pregnancy. PMID- 11208323 TI - Subpopulations of the peripheral lymphocytes in the early clinical forms of Lyme disease. AB - The evaluation of the changes of lymphocytes: T(CD3), B (CD19), subpopulations CD4, CD8, active lymphocytes CD3 + HLA-DR+, lymphocytes with the receptor for IL2(CD3 + CD25+), NK cells as well as the CD4/CD8 ratio in 30 patients with the early localized (group I n = 7) and early disseminated (group II n = 23) type of Lyme disease, before (examination 1) and after the antibiotic therapy (examination 2) was performed. Group III was composed of 90 healthy people. Measurements were carried out in an COULTER EPIC XL cytoflowmeter, using Becton Dickinson antibodies. Statistical analysis was performed using AnStat software. In the examined groups, a decrease of the subpopulations of CD4, CD8 lymphocytes in comparison with healthy subjects was revealed, as well as a decrease of the CD4/CD8 ratio after treatment. A considerably lower percentage value of active lymphocytes CD3 + HLA-DR+ in both groups and the reduction of the NK subpopulation before and after treatment of early disseminated Lyme disease in comparison with healthy people was observed. The higher percentage values of the lymphocytes with IL-2 receptor were not statistically significant. The indicated essential changes in the subpopulations of T lymphocytes, characterized by a decrease before the antibiotic therapy and by the tendency towards an increase after that therapy of the percentage of CD4, CD8, NK and CD3 + HLA-DR+ lymphocytes in peripheral blood, point out their role in the immunopathogenesis of the Lyme disease. The absence of the complete normalization of the examined parameters after the treatment, on the one hand, may provide evidence for some inertia of the elements of the immune system, on the other hand can also result from too short antibiotic therapy and maintenance of the antigenic stimulation. PMID- 11208324 TI - Comparison of bacterial flora found in the peritoneal cavity and drains after intraabdominal surgery. AB - The aim of this study was to evaluate bacterial flora infecting during the surgical procedures the peritoneal cavity and drains which were used after the surgery in 40 patients who underwent surgery for colon and rectum tumors. Smears from the peritoneal cavity, liquid removed from the drain taken at 3-4 days after the surgery and smears from the drain taken at the end of drainage of each patient were examined for bacterial content. The comparison of bacterial flora found in the peritoneal cavity with bacteria found in drains showed that the frequency of isolation of anaerobes decreased in contrast to aerobes which were more often cultured over the time of drainage (p < 0.05). Bacteroides spp, enterococci, and strains of Enterobacteriaceae were most often isolated from the peritoneal cavity, but over the time of drainage the frequency of isolation of coagulase-negative staphylococci including MRCNS increased as well as the number of patients infected with enterococci, whereas anaerobes and strains of Enterobacteriaceae were rarely isolated. PMID- 11208325 TI - Adherence of bile-isolated bacteria to the bile ducts mucosa as a pathogenic factor in the development of inflammatory lesions. AB - Bacterial infection of the bile system appears to be an important factor in the formation of stones. In view of the hypothesis that strains of E. c. form an essential factor in infections of the bile ducts, an attempt has been made to determine the connection between infections of the bile ducts and the adherence of E. c. to the epithelium of the gallbladder. The research covered 148 patients operated electively for cholecystolithiasis (121), cholecystocholedocholithiasis (26) and recurrent lithiasis (1). In bile collected from the gallbladder in the course of the operation, E. coli strains were isolated. Cholangioscopy performed in 26 patients enabled the macroscopic evaluation and grading of inflammatory lesions of bile duct mucosa. The mucosa of the gallbladder was evaluated histologically. The adherence test was performed using homologous and heterologous strains of E. c. isolated from the bile of gallstone patients. The adherence occurred most frequently in the neck of the gallbladder (71-100%) in those patients in whom an infectious process of the bile ducts mucosa was endoscopically diagnosed. The adherence of bacteria to the epithelium of the gallbladder did not depend on the type of inflammation (acute, chronic). PMID- 11208326 TI - Antibiotic-sensitivity of Moraxella catarrhalis isolated from clinical materials in 1997-1998. AB - Moraxella catarrhalis (M. catarrhalis) may normally be found in the upper respiratory tract. This bacterium, however, may cause infections such as acute otitis media, sinusitis, conjunctivitis, bronchitis chronica, pneumonia, endocarditis, septicaemia and meningitis. Haemophilus influenzae, Streptococcus pneumoniae and M. catarrhalis were the main causative agents responsible for respiratory tract infections. The major resistance problems associated with these species are those which cause resistance to beta-lactams. beta-lactamase was produced by > 80% M. catarrhalis strains. The susceptibility to ampicillin, amoxicillin/clavulanic acid, cefuroxime, erythromycin, ciprofloxacin was tested in 137 M. catarrhalis strains. All the strains resistant to ampicillin produced beta-lactamase and were sensitive to amoxicillin/clavulanic acid. For M. catarrhalis, the most active antimicrobials included cefuroxime (99%), ciprofloxacin (99%) and erythromycin (93%). PMID- 11208327 TI - Influence of rectus eye muscles tenotomy on the aqueous humor composition in rabbits. AB - INTRODUCTION: Anterior segment ischaemia manifesting in aqueous malformation may follow tenotomy of the extraocular muscles. MATERIAL AND METHODS: Tenotomy of 2 or 4 rectus eye muscles was performed on the right eyes of 23 adult rabbits. The aqueous humor was withdrawn from the anterior chamber of both eyes in 7 rabbits on the 11th, on the 22nd in 8 and on the 32nd postoperative day in 8 rabbits. Aqueous natrium, potassium and glucose concentrations and protein electrophoresis were examined. RESULTS: The only significant change was lower mean aqueous potassium concentration in the operated eyes as compared to controls on the 11th postoperative day. CONCLUSION: Tenotomy of rectus eye muscles in healthy rabbits evoked a discrete blood-aqueous barrier break-down. PMID- 11208328 TI - Correction of hypertensive cardiac remodelling: comparison of different antihypertensive therapies. AB - The aim of the study was to compare the effects of long-term treatment with different types of antihypertensive drugs on left ventricular hypertrophy (LVH) and diastolic function in patients with essential hypertension. We examined 60 patients with mild to moderate hypertension from 35 to 55 years old (middle age 44.3 +/- 2.3 yrs) having no concomitant diseases. Patients were treated for six months with different types of antihypertensive drugs: 21 patient received nifedipine-retard 40 mg/day, 20--atenolol 100 mg/day, 10--losartan potassium 100 mg/day, 9--perindopril 4 mg/day. Cardiac structure and function was studied by echocardiography. For the left ventricle (LV) the diastolic mass normalised for body surface area (LVMI), the ratio of the early and atrial mitral inflow velocities (E/A), isovolumetric relaxation time (IVRT), relative wall thickness (RWT) were measured. After six months of treatment LVMI decreased by 9% in nifedipine group (P < 0.01), by 10.5% in atenolol group (P < 0.01), by 12% in losartan group (P < 0.01) and by 8.2% in perindopril group (NS). RWT decreased in all groups, while diastolic dimension index remained unchanged. The reversal of LVH was not related to blood pressure reduction. It was more significant in patients with initially higher values of LVMI. Antihypertensive effects of the drugs were comparable. Long-term treatment with all types of selected drugs improves cardiac structure and function independently of their antihypertensive action. Our data suggest that on the basis of the influence on cardiac remodelling no preference for any studied drug can be discerned. The work had the following source of support: the atenolol (Falitonsin) and nifedipine-retard (Corinfar-retard) were provided by the AWD Company (Germany), losartan potassium has been provided by Merck Sharp & Dohme Company and perindopril (Prestarium) by the Servier Group. PMID- 11208329 TI - Age and sex as factors modifying the function of the blood-cerebrospinal fluid barrier. AB - INTRODUCTION: The aim of the study was to find out, if there was a difference in function of the blood/cerebrospinal fluid barrier (BCSFB) in females and males, and if those differences intensify with age. MATERIAL AND METHODS: 120 patients of both sexes who underwent subarachnoideal anesthesia were divided into 6 groups, 20 patients each, considering sex and age criteria. Samples of venous blood (5 ml) and cerebrospinal fluid (1 ml) were collected from every patient simultaneously; then albumin permeability indexes (Qalb) were counted. The achieved results were compared using the t-Student test at the significance level of P < or = 0.05. RESULTS: The mean value of Qalb in patients aged 20-50 was significantly lower than in the group of patients aged 51-70, as well as in the group of patients over 71. The difference between mean Qalb values in patients aged 51-70 and those aged over 71 was also statistically significant. No statistically significant difference between mean Qalb values in females and in males in the corresponding age groups was found. In every age group the value of albumin permeability index was lower in females. CONCLUSIONS: 1) The permeability of BCSFB increases with age. 2) There was no statistically significant difference between the values of albumin permeability index in females and males in the corresponding age groups. The function of BCSFB in the corresponding age groups of males and females was the same. PMID- 11208330 TI - Comparison of influence of thiopentone, propofol and midazolam on blood serum concentration of noradrenaline and cortisol in patients undergoing non-toxic struma operation. AB - The stress hormones plasma concentration after intravenous anesthetics (thiopentone, propofol, midazolam) administration in patients who underwent non toxic struma operation was estimated. The goal of the study was to answer what stage of the general anesthesia and the surgery is the most dangerous for the cardiovascular system in term of stress hormones concentration and which of induction anesthetics used significantly alleviates undesirable reactions to surgical trauma and general anesthesia. 45 women aged 43 +/- 11, who underwent non-toxic struma operation and 16 women who underwent biliary gall-stones operation served as the 'study group and controls', respectively. Both groups were divided into 3 subgroups (in each a different anesthetic was used). Blood samples were taken at moments of increased stress during general anesthesia and operation. Intubation performed by laryngoscopy was found as the most stressful moment at which stress hormones are released intensively and can initiate cardiovascular disorders. According to our investigations, the suppression of the stress hormones (noradrenaline and cortisol) release was observed when propofol and midazolam were used for anesthesia induction for non-toxic struma surgery in contrast to thiopentone administration. PMID- 11208331 TI - Comparative analysis of plasma lipoprotein components assessed by ultracentrifugation in primary biliary cirrhosis and chronic hepatitis. AB - The evaluation of lipid and lipoprotein profiles in liver diseases has important cognitive aspects and provides practical information contributing to the diagnosis of liver pathology. There are few studies of this problem using the ultracentrifugation method. AIM OF THE STUDY: A comparison of lipid profile (obtained by plasma ultracentrifugation) in patients with primary biliary cirrhosis (PBC) and chronic hepatitis (CH). MATERIAL AND METHODS: 103 percutaneous liver biopsies were routinely performed from 1994 to 1997. Blood samples were taken from all the patients at the time of biopsy for further evaluation of lipid profile. 15 patients with PBC and 15 patients with CH (of HBV or/and HCV etiology) were studied. RESULTS: In patients with CH mean total, esterified and free cholesterol levels (166 mg%, 117.6 mg% and 48.1 mg%, respectively) were significantly lower (p < 0.002; p < 0.004; p < 0.006, respectively) than in patients with PBC (237.5 mg%, 165.7 mg% and 71.8 mg%, respectively). The phospholipid concentration in sera of patients with PBC were significantly higher (271.1 mg%, p < 0.0004) than in patients with CH (187.6 mg%), whereas apolipoprotein B and apoAII were significantly lower. Total, esterified and free cholesterol levels in LDL fraction were significantly higher in patients with PBC (175.3 mg%, p < 0.007; 117.9 mg%, p < 0.02; 57.6 mg%, p < 0.01, respectively) than in patients with CH (113.7 mg%, 78.7 mg% and 35 mg%, respectively). The concentration of phospholipids in LDL fraction in patients with PBC was significantly higher (166.8 mg%; p < 0.003) in comparison with patients with CH (96.3 mg%). The differences in other lipoprotein fractions (VLDL and HDL) were not statistically significant. CONCLUSIONS: High levels of total, free and esterified cholesterol as well as phospholipids, apolipoprotein B and AII were observed by us in patients with PBC in comparison with patients suffering from CH. The increase of cholesterol (total, esterified and free) and the phospholipid concentration in serum, are a manifestation of their higher concentration in LDL fraction. PMID- 11208332 TI - Comparison of clinical features of cholecystolithiasis and functional dyspepsia. AB - 148 patients with cholecystolithiasis and 77 patients with functional dyspepsia were examined to isolate symptoms or a syndrome characteristic of 'pure' (i.e. uncomplicated and without any co-existing diseases) cholecystolithiasis and functional dyspepsia; to evaluate their specificity and sensitivity as well as to estimate the power of each symptom or a group of symptoms to differentiate both these conditions. Endoscopy, ultrasound scan and biochemical tests were performed in each patient to exclude co-existence of any other gastrointestinal disorders. Also irritable bowel syndrome was excluded according to Manning's criteria. It was found that both these conditions have most often seven co-existing dyspeptic symptoms and that each symptom separately has low sensitivity and specificity for cholecystolithiasis as well as functional dyspepsia. The diagnostic power of each symptom is weak and even summing them up into groups of symptoms does not increase their diagnostic power. PMID- 11208333 TI - HLA class I haplotypes in families of children with coeliac disease. AB - The purpose of the study was the analysis of HLA-AB haplotypes frequency in the families of children with coeliac disease. Haplotypes present in 46 probands' families including 69 affected children, 49 healthy siblings and 91 parents were verified. HLA antigens were typed by Terasaki and McClelland's routine two-step microcytotoxic assay in NIH modification. Among 138 haplotypes, the following were significantly more frequent in affected children: HLA-A1-B8 (3116 x 10(4)), HLA-A3-B8 (290 x 10(4)) and HLA-A2-B8 (217 x 10(4)). Total frequency of haplotypes including HLA-B8 antigen in comparison to control population equalled 3986 x 10(4) vs. 763 x 10(4). HLA-A1-B8 haplotype frequency was twice lower in probands' healthy siblings and parents, equalling 1837 x 10(4) and 1868 x 10(4), respectively. Highly significantly more frequent HLA-A1-B8 haplotype found in probands' families may indicate the correlation between inherited gene products and increased risk of coeliac disease incidence. PMID- 11208334 TI - Association of lipid metabolism with subclinical diabetic cardiomyopathy in children and adolescents with type 1 diabetes. AB - Nowadays, it is known that atherosclerosis is not a disease affecting elderly people but that it starts as early as in childhood. Children with diabetes mellitus are particularly prone to early development of atherosclerosis. It seems advisable to evaluate the behaviour of lipoprotein (a), apolipoprotein B (atherogenic factors), and apolipoprotein A-I in this group of patients as possible causal or preventive factors of the developing diabetic cardiomyopathy. The purpose of this study was to evaluate the effect of the intensification of lipid metabolism disorders on systolic-diastolic parameters of heart ventricles in children and adolescents with insulin-dependent diabetes mellitus. The study was performed on 19 children and adolescents (11 boys and 8 girls) at the age of 8.4-18.5 (x = 14.2) who have had insulin-dependent diabetes mellitus for 1.5 to 14 years (x = 7.9 years). Control group consisted of 17 healthy children. All patients were subjected to full echocardiographic examination which measured the systolic-diastolic activity of both heart ventricles, and to examinations determining the presence of complications (including the subclinical ones). Additionally, patients had their lipid metabolism parameters defined, i.e.: Lp(a), apo A-I, apo B, triglycerides, cholesterol and its LDL and HDL fractions. CONCLUSIONS: 1. Children and adolescents with type 1 diabetes mellitus have higher concentration of Lp(a) and apolipoprotein B irrespective of the degree of diabetes control, which makes them prone to premature development of atherosclerosis. 2. Lipid metabolism disorders do not have direct influence on the development of diabetic cardiomyopathy in young patients with type 1 diabetes mellitus. PMID- 11208335 TI - Gastroesophageal reflux in infants with food allergy. AB - The authors present results of studies in a group of 58 children aged 4-36 months in whom food allergy has been diagnosed. Esophageal 24-hour pH-metric studies revealed the presence of gastroesophageal reflux (GER) in 27 cases (46.5%). In 13 cases it was primary and independent of the allergic disease, and in 14 children it showed features of secondary gastroesophageal reflux. Conservative treatment appeared ineffective more frequently in the group of infants with primary reflux (in 23.1% of cases) than in children with secondary reflux and food allergy (in 7.1% of cases). In 4 infants fundoplication according to Nissen was performed. PMID- 11208336 TI - Plasma levels of sICAM-1 in patients affected by psoriasis: no relation to disease severity. AB - The aim of the study was to determine the plasma level of sICAM-1 in acute psoriatic patients in contrast to normal subjects. Moreover, we have tried to answer whether disease severity index (PASI) correlates with plasma level of sICAM-1. We have determined the plasma levels of sICAM-1 by ELISA (Genzyme Corporation) in 23 patients with acute psoriasis before and after the treatment of the disease and in 11 controls. Patients with acute psoriasis have displayed higher levels of sICAM-1 (306.4 +/- 226.8 ng/ml) compared with the controls (141.2 +/- 49.2 ng/ml) and the same patients after clearing of the disease (154.7 +/- 126.7 ng/ml). We have not found any correlation between plasma levels of sICAM-1 and severity index of psoriasis (PASI). We have concluded: the plasma levels of sICAM-1 are not related to disease severity in acute psoriasis. Clearing of the psoriasis is followed by significant fall of plasma sICAM-1. PMID- 11208337 TI - Clinical and parasitological appraisal of patients with imported malaria. AB - The study group comprised 118 patients suspected of malaria who underwent an examination following their return to Poland from the tropical countries. Evaluation of the admitted patients was based on epidemiological, clinical and parasitological criteria. The obtained data allowed to confirm acute malaria in 20 patients (16.9%) and malaria in the past, in 32 patients (27.1%). In the remaining 65 patients (55.1%) we excluded malaria. Malaria caused by P. vivax was confirmed in 5 patients, by P. falciparum in 9 patients. A mixed invasion was diagnosed in 6 patients including: P. falciparum and P. vivax in 3 cases; P. vivax, P. ovale and P. malariae in 2 cases; P. falciparum, P. vivax and P. ovale in 1 patient. We noted no relationship between the severity of the clinical course and IFA results. It was found an atypical clinical course of malaria and diagnostic difficulties in patients who used chemosuppression for malaria prophylaxis. PMID- 11208338 TI - Hepatitis C virus infection in hospitalized children. AB - AIM: The aim of the study was the estimation of the incidence of HCV infection and the analysis of risk factors for the infection in hospitalized children. MATERIAL AND METHODS: Retrospective analysis of the data of 1263 patients treated in hospital wards of Chair and Department of Gastroenterology and Paediatric Diseases from July 1995 to March 1998; all the patients had hepatitis C virus antibodies determined. Hepatitis C virus antibodies were assessed with the use of enzyme immunoassay. All the positive results were confirmed by means of Lia Tek HCV or PCR HCV RNA method. History data regarding frequency of previous hospitalizations, operations, blood transfusions and invasive diagnostic procedures patients had undergone were included in analysis. RESULTS: HCV infection was diagnosed in 47 children which accounted for 3.7% of the group enrolled in the study. The majority, that is 96.2% of seropositive children had the history of hospitalization, while 73.2% of them underwent intervention procedures disrupting tissue continuity during previous hospitalizations. Physical examination analysis indicates that all the patients with antibodies against HCV could have acquired the infection through parenteral transmission. The data indicating another route of transmission were not obtained (e.g. familial transmission). CONCLUSIONS: 1. Serological tests for HCV infection should be performed on routine basis in frequently hospitalized children. 2. HCV infection resulting from iatrogenic transmission can be suspected in the majority of seropositive children. PMID- 11208339 TI - Peptic ulcer disease before and after introduction of new drugs--a comparison from surgeon's point of view. AB - During the last twenty years we have witnessed a revolutionary change in treatment and diagnosis of peptic ulcer disease (PUD). It was introduction of flexible fiberoptic instruments and new drugs: H-2 blockers, proton pump inhibitors (PPI) and treatment against Helicobacter pylori which affected most significantly the course of this illness. Although indications for surgical intervention have not been changed, practice of surgery in this regard has changed a lot. In this report two periods of time were analyzed and compared: years 1977-81 and 1992-96. Operation reports from the above defined periods were reviewed and all surgeries performed for PUD and its complications have been noted along with data regarding patients and indications for surgery as reported by operating surgeons. There were 360 surgeries for PUD performed in the 1977 1981 period, and 246 in the years 1992-1996. Patients were divided into groups depending on indications for surgery. A significant reduction in the general number of operations performed was noted. The percentage of women operated upon increased. The mean age of patients in all indication groups was higher in the latter period. Patients operated for bleeding tended to be older than those in perforation and intractable disease groups. This was true in both periods of time. The number and percentage of patients operated for perforation increased. The natural course of PUD is changing; intractable disease as an indication for surgery is disappearing, the number of pyloric obstruction patients is diminishing, the incidence of bleeding and perforation remains constant. The mean age of patients and percentage of women is increasing. PMID- 11208340 TI - Perforated peptic ulcer--time trends and patterns over 20 years. AB - There are contradictory reports in current world literature regarding incidence of perforated peptic ulcers and male to female ratio in recent years. Old concepts of seasonal periodicity are being questioned. In our report we analyze what is changing with regard to demographical data of patients affected, incidence of perforation of peptic ulcer and ulcer location. This article reviews 441 consecutive cases of this complication of peptic ulcer disease (PUD) treated in our department between January of 1977 and December of 1996. The source of analyzed data are operative reports. Several observations regarding number, age and sex of patients affected and ulcer location have been made. PMID- 11208341 TI - Application of cytology in diagnosing benign changes and breast cancers. AB - On the basis of cytology performed in a group of 386 women and 14 men admitted to the Breast Disease Outpatient Unit in the area of Sucha Beskidzka, a structure of changes in breast benign and malignant neoplasms was defined. The diagnostic value of cytology based on FNB and a secretion from mammary glands were evaluated. Expression of p53 and nm23 protein expression in the cells of the most common cancers was studied for prognostic values. The study demonstrated 81% of benign changes and 19% of cancers. With respect to cancers, cytology confirmed its usefulness since the findings were compatible in 94.44% with histopathologic results. Moreover, application of proliferation markers (p53 and nm23) allowed to evaluate the degree of malignancy and prognosis for further neoplastic process. PMID- 11208342 TI - Pulmonary sarcoidosis in a patient with essential thrombocythemia treated with interferon alpha: a short case report. AB - A patient with essential thrombocythemia was diagnosed with pulmonary sarcoidosis after interferon alpha therapy. Following interferon treatment the miliary pulmonary dissemination has appeared and after disruption of this therapy it resolved during two months. Few cases of sarcoidosis associated with interferon alpha treatment have been reported. These patients were treated for chronic myelogenous leukemia, chronic hepatitis C, and renal cell carcinoma. We report the first case of interferon-related sarcoidosis in an essential thrombocythemia patient. PMID- 11208343 TI - Neurogenic tumors of the digestive tract: report of two cases. AB - We report two female patients with neurogenic tumors of the digestive tract. In the first patient, the tumor of 10 cm diameter originated in the stomach and at preoperative CT imitated a peripancreatic cyst. In the second patient, the tumor of 6 cm diameter originated in the duodenum. Despite large size, the tumors were clinically indolent and escaped detection at routine endoscopic evaluation. In both cases the neoplasm was removed and postoperative histopathology combined with immunohistochemistry was consistent with diagnosis of digestive Schwannoma. PMID- 11208344 TI - Paroxysmal atrial fibrillation in a young female patient following marijuana intoxication--a case report of possible association. AB - Marijuana is one of the most popular drugs legally admitted for general sale in many countries. To consider it safe and unlikely to develop drug dependence is abusive. The use of marijuana as a herbal medication is being widely discussed in literature. The most promising effect of delta-9-etrahydrocannabinol seems to be observed in the case of nausea, following cancer chemotherapy. Despite its positive action on the human organism, marijuana smoking has been shown to exert adverse effects on the cardiovascular system causing well-tolerated tachycardia and/or hypotension. We also observed that marijuana abuse was associated with an increased risk of paroxysmal atrial fibrillation. The report presents a case of young healthy white subject suffering from paroxysmal atrial fibrillation following marijuana intoxication. The abuse of this substance was the most possible and identifiable risk factor for observed paroxysmal atrial fibrillation. PMID- 11208345 TI - False aneurysms of the proximal anastomosis of the arterial prosthesis and the abdominal aorta. AB - Due to a false aneurysms of the aortic-prosthetic anastomosis ten patients aged 42-74 years underwent surgery. In three patients, an aneurysm occurred twice. One was operated on after the aneurysm had ruptured. Six patients were treated for hypertension. In the course of the primary procedure, in six cases aortic bifemoral grafts were implanted, in four--an aortic-femoral, and in two aortic biiliac grafts were used. In six patients end-to-end anastomoses were performed, and in four--end-to-side. Surgical corrections due to the occurrence of a false aneurysm were performed 3 months to 10 years after the original surgery. On reoperation, purulent matter was found in the site of the prosthesis. In two patients, aortic-intestinal fistulas were detected, and in one--an aortic-cecal fistula. In six patients the anastomoses were totally separated. In the course of 13 procedures performed in false aneurysms, five times replaced, single sutures were applied to the entire circumference of the anastomosis in four cases, including one case where an oblong patch was also used, in three cases an extra segment was sutured between the aorta and the previously implanted prosthesis, and the aneurysmal sac was filled with wire in one patient. Eight patients were reoperated, including three repeated procedures due to a false aneurysm of the proximal anastomosis. Moreover, the patency of prostheses was restored, abscesses were surgically opened and procedures were performed in the colon. Four patients have survived, including one with bilateral amputation of lower limbs. The most common cause of death was myocardial infarction. Two patients died due to massive hemorrhage, and one as a result of uremia. PMID- 11208346 TI - Endometrial cancer in patients with breast carcinoma treated with tamoxifen: report of two cases and the literature overview. AB - Tamoxifen (TAM) is the endocrine treatment of choice in the first-line therapy for all stages of breast cancer, in both pre- and postmenopausal women. Some clinical studies indicated a small but significant increase in the risk of subsequent endometrial carcinoma in breast cancer women who take TAM as an adjuvant therapy. In this study, we present two cases of breast cancer patients in whom endometrial cancer was diagnosed during TAM treatment; the current status of knowledge on the relationship between TAM use and the risk of endometrial cancer is reviewed. PMID- 11208347 TI - Thermographic assessment of stellate ganglion block effectiveness during cardiosurgical procedures. AB - The study present thermographic assessment of the effectiveness of temporary stellate blockade performed during cardiosurgical procedures. The assumption behind this method was the increase in the temperature of upper extremity on the side of blockade, due to the broadening of arterial bed. MATERIAL AND METHOD: The study was conducted on a group of 30 patients (21 men and 9 women) operated due to coronary disease involving three vessels. Mean age of the patients was 53 years. After introduction of anaesthesia blockade were performed with 2 ml 2% lignocainum and 8 ml 0.5% bupivacaine solution using peratracheal approach. Blockade effectiveness was assessed on the basis of images obtained in thermovisual camera, comparing the temperatures of upper extremity before and within 15 minutes after performing the blockade. Free blood outflow from radial artery, its diameter and length were also evaluated. The results obtained were subject to statistical analysis. RESULTS: Twenty-three patients (76.6%) displayed the increase in the temperature of upper extremity by 1-3 degrees C. Free blood outflow from radial artery was greater in this group than in the remaining patients. CONCLUSIONS: Thermography is a useful method for the assessment of stellate blockade effectiveness. Effective blockade results in the increased blood flow in radial artery. PMID- 11208348 TI - Anthracycline-induced cardiotoxicity: clinical course, risk factors, pathogenesis, detection and prevention--review of the literature. AB - Anthracycline antibiotics are widely used antineoplastic agents and their efficacy for the treatment of various haemopoietic or solid tumours has been well established in clinical practice. Cardiotoxicity is one of the most serious side effects of anthracyclines. The risk of cumulative, life-threatening toxic cardiomyopathy limits their therapeutic potential. In this article, acute, subacute, chronic and late-onset cardiac function impairment associated with anthracycline administration has been characterised. The current views on the methods of detection, pathogenesis and prevention of such toxicity have been reviewed. PMID- 11208349 TI - Myeloproliferative disorders--neurological complications. AB - Primary myeloproliferative disorders (MPD) are often associated with hemostasis abnormalities, which may cause many thrombotic or hemorrhagic complications during the course of the disease. Clinical consequences following abnormal hemostatic conditions include various neurological manifestations. It is extremely difficult to predict and evaluate the risk and chance, that MPD patients will develop neurological symptoms. The up-to-date background of pathological thrombocytosis, as well as the neurological aspects of abnormal hemostasis during the course of myeloproliferative disorders have been reviewed in this study. PMID- 11208350 TI - Head trauma and neuroprotection. AB - Traumatic brain injury is a serious clinical problem connected with high mortality rate and long-term neurobehavioral and socioeconomic consequences. Pathomechanism of such insult is complex and not clear in all aspects as yet. Thus, a primary mechanistic insult to the brain initiates metabolic and inflammatory processes which exacerbate the primary traumatic injury to neurons, leading to secondary brain damage. In this paper we present the main components of destructive cascade with relevant theoretical strategy for neuroprotection. It should be emphasized that pathological processes involved in secondary brain damage are complex and interrelated. It makes blockade of a single mechanism unlikely to prevent either early or delayed cellular death. PMID- 11208351 TI - Androgens and androgen receptor: do they play a role in breast cancer? AB - Although the role of androgens and AR in breast cancer genesis, development of breast cancer and tumor responsiveness to endocrine therapies is poorly understood, the widespread expression of AR suggests that it may be of biological and clinical importance in human breast cancer. PMID- 11208352 TI - Experimental model of hepatic venoocclusive disease (VOD) caused by dactinomycin- preliminary report about hepatoprotective effect of amifostine. AB - The purpose of the study was elaboration of the experimental model of hepatic venoocclusive disease (VOD) induced by dactinomycin and investigation of possible hepatoprotective effects of amifostine and heparin individually or in combination with dexamethasone. 198 Wistar strain male rats were used in the trial in two series of experiments. In the first series the experimental model of VOD induced by dactinomycin was elaborated on the group of 18 animals (divided into 3 groups receiving intraperitoneally isotonic salt solution, dactinomycin or nitrosamine). Nitrosamine--a well-known agent causing VOD--was used as positive control. Open biopsies of the liver and blood collections were repeated in order to determine liver enzymes' concentrations. Histopathological examinations demonstrated that dactinomycin caused liver lesion corresponding with VOD picture. Second series of animals was divided into 6 groups receiving the following drugs: I--0.9% NaCl solution, II--dactinomycin (ACT), III--ACT + fraxiparine s.c., IV--ACT + fraxiparine + dexamethasone, V--ACT + amifostine. Five animals from each group were sacrificed on the 3rd and 7th day after each cycle of drug administration. Blood was drawn in order to determine the following: AspAT, AlAT, Falk, GGTP and LDH. Intravital wedge biopsies under anesthesia with the use of inactin were also performed. Liver samples were stained with the use of H&E, p. a. S and Gomory's techniques. We did not find significant differences in liver enzymes' levels between the groups. Pathological changes corresponding with VOD picture of different intensification were found in liver samples from all the rats receiving ACT. Changes became more and more intensive after consecutive cycles. Lesion of central veins' and liver sinusoids' endothelium dominated. Fraxiparine administered individually or in combination with dexamethasone did not prevent the lesion. Administration of amifostine before ACT decreased pathomorphological changes in liver. Dactinomycin caused homogenous subclinical liver lesion corresponding with VOD. It may also occur in children receiving ACT in the course of nephroblastoma's treatment. But probably the changes are too subtle to manifest themselves clinically with exception of patients particularly sensitive (for example after previous radiotherapy). Lack of differences observed in liver enzymes' levels between the groups supports the explanation. Markers of lesion of liver vessels' endothelium should be looked for to make more specific diagnostics of VOD possible. Hepatoprotective properties of amifostine need further studies. CONCLUSIONS: 1. It is possible to create the experimental model of VOD induced by dactinomycin administration. 2. Amifostine seems to act hepatoprotectively to liver lesions caused by dactinomycin. PMID- 11208353 TI - Stimulation by nitric oxide of HCO3- secretion in bullfrog duodenum in vitro- roles of cyclooxygenase-1 and prostaglandins. AB - The effect of nitric oxide (NO) on HCO3- secretion was examined in vitro using the isolated preparation of bullfrog duodenum, in relation to cyclooxygenase (COX) isozymes and endogenous prostaglandins (PGs). The tissue was bathed in unbuffered Ringer solution gassed with 100% O2 on the mucosal side and HCO3- Ringer's solution gassed with 95% O2-5% CO2 on the serosal side. The HCO3- secretion was measured by a pH-stat method using 10 mM HCl as the titrant to keep the mucosal pH at 7.4. NOR-3 [(+/-)-(E)-Ethyl-2-[(E)-hydroxyimino]-5-nitro-3 hexenamine] was used as a NO donor and added to the serosal solution. To analyze the NOR-3 action, the effects of dibutyryl guanosine-3', 5'-cyclic monophosphate (dbcGMP), methylene blue, indomethacin (nonselective COX-inhibitor) and NS-398 (selective COX-2 inhibitor) on the HCO3- response were also examined. NOR-3 (1 x 10(-4) and 3 x 10(-4) M) caused an increase of HCO3- secretion in a dose dependent manner, reaching the level of 2.5 times greater than basal values at 2 hr later. Likewise, dbcGMP (1 x 10(-3) M) also caused a significant increase of the duodenal HCO3- secretion. The HCO3- stimulatory action of NOR-3 was significantly attenuated by methylene blue (5 x 10(-5) M) and indomethacin (1 x 10(-5) M) but not by NS-398 (1 x 10(-5) M), and indomethacin also suppressed the HCO3- response to dbcGMP. The serosal release of PGE2 was significantly increased by both NOR-3 and dbcGMP, and these responses were inhibited by indomethacin but not NS-398. These results suggest that NO increases HCO3- secretion in Bullfrog duodenum in vitro, and this action is dependent on cGMP-related COX-1 activation and mediated by PGs. PMID- 11208354 TI - Catalytic heterogenity of polyclonal RNA-hydrolyzing IgM from sera of patients with lupus erythematosus. AB - Various catalytically active IgG antibodies or abzymes have been detected recently in the sera of patients with several autoimmune pathologies including systemic lupus erythematosus (SLE), where their presence is most probably associated with autoimmunization. Here we show for the first time that IgM from peripheral blood of patients with SLE possesses both DNase and RNase activities: these activities were also present in Fab fragments of the IgM. Both specific enzymic activities of IgM from sera of any single patient are usually 5-10 times higher than those of IgG antibodies. The same preparations of IgM hydrolyze RNA about two order of magnitude faster than DNA. The properties of the RNases of IgM and IgG distinguished them from other known pancreatic and human sera RNases. In addition, the specific activities of the RNase activity of polyclonal IgM with the polymer substrates [RNA > poly(U) > or = poly(A) >> poly(C)], the observed range of optimal pHs, of apparent Km values for substrates and of substrate specificities varied very much for different patients. The findings speak in favor of the generation of a relatively small or an extremely large pool of polyclonal catalytic IgM by the immune system of individual patients. PMID- 11208355 TI - Effect of melatonin on two stage skin carcinogenesis in Swiss mice. AB - Melatonin, a hormone secreted by the pineal gland, is known to have anti mutagenic and oncostatic actions. This beneficial action of melatonin has been explained in terms of its ability to scavenge free radicals and augment the activities of anti-oxidant enzymes. In the present study, we evaluated the effect of melatonin on benzo(a)pyrene-induced two stage skin carcinogenesis in mice and observed that it can not only decrease the number of animals bearing papillomas but also the number of papillomas per animal both in the initiation and promotion stages of skin carcinogenesis. It was also found that melatonin treated animals have low levels of lipid peroxides and that it can also prevent the binding of BP or its metabolites to DNA. In view of these evidence, it can be suggested that melatonin may function as an endogenous anti-mutagenic and oncostatic agent. PMID- 11208356 TI - Changes in abdominal wall after mesh implantation in rats. AB - On an incisional hernia model, we evaluated tissue reactions to three types of non-absorbable foreign materials, Prolene, Gore-Tex and flax, used for covering defects of the abdominal wall muscles in Wistar strain rats. The examinations were carried out in five 14-days intervals between the 35th and 91st days after the intervention. Our results with Gore-Tex showed the lowest tissue response, the lowest inflammatory cellular as well as fibroplastic reaction, it also completely covers the artificially made wall defect and induces no considerable peritoneal adhesion. In defects filled with Prolene mesh, we also observed no considerable cellular response and scarring. However, considerable peritoneal adhesions were found and the defect was filled to a great extent with lipidic tissue with irregularly distributed Prolene fibres. The use of flax material is least suitable since it induces extensive inflammatory reactions, which occur even after a very long time after the operation. Prolene was, as a matter of fact, second to Gore-Tex in the experimental evaluation of the biological tolerance. However, with respect to its ten times lower price, it can be recommended as a material of the first choice for covering defects of the abdominal wall in clinical use. PMID- 11208357 TI - Nitric oxide increases gene expression of Ca(2+)-ATPase in myocardial and skeletal muscle sarcoplasmic reticulum: physiological implications. AB - The aim of the study was to verify the hypothesis that NO-dependent regulation of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) gene expression can play an important role in prevention of calcium overload under the influence of detrimental factors. It was shown that 2 hours after the administration of the NO donor dinitrosyl iron complex (DNIC), the gene expression of myocardial SERCA was increased by 20% as compared to the control. In skeletal muscles, the maximum increase in SERCA expression was observed in 6 hours and amounted to 156% as compared with the initial value. Simultaneously DNIC enhanced the resistance of isolated heart and the organism as a whole to damaging effects of intracellular calcium overload induced by post-ischemic reperfusion or vigorous exercise, respectively. The results obtained confirm the existence of NO-dependent activation of SERCA expression and the important role of this mechanism in restriction of calcium overload. PMID- 11208358 TI - Effect of the ligation of spleen neurovascular pedicle on the morphology of hemolymph splenic nodes in Wistar rats. AB - Macro- and microscopic structure of hemolymph splenic nodes after ligature of spleen neurovascular pedicle was evaluated in 12 Wistar rats. The results obtained were compared with the nodes of the control group. It was found that spleen neurovascular pedicle ligation without removing the organ from abdominal cavity results in the enlargement of examined nodes and a change in their color intensity. Histological examination revealed considerable increase in erythroid elements filling mainly the medullary part of the node. The spleen underwent total atrophy. Retrogressive changes, typical for single-organ nodes were not observed. Non-hemolymph mesenteric nodes did not show any macroscopic compensatory changes. PMID- 11208359 TI - An attempt to assess the central action of captopril and enalaprilat. AB - The influence of captopril and enalaprilat on central nervous system in laboratory animals has been studied. The effects of the drugs on duration of ethanol (4 g/kg i.p.) and thiopental (70 mg/kg i.p.) induced sleep, body temperature, spontaneous locomotor activity and analgesic properties (hot plate and tail-flick test) have been investigated in mice. Captopril (5 and 20 mg/kg i.p.) and enalaprilat (5 and 20 mg/kg i.p.) were used in single administration or repeated one for 10 days. Moreover, pharmaco-EEG profile of captopril and enalaprilat in rabbits has been studied. We have shown that single administration of captopril (both doses) and single or prolonged administration of enalaprilat decreased the duration of ethanol and thiopental-induced sleep. Captopril (5 mg/kg) and enalaprilat (5 and 20 mg/kg) increased pain threshold. Both studied drugs after their single or repeated administration did not influence spontaneous locomotor activity in mice. Captopril and enalaprilat decrease body temperature in mice. Examined ACEIs produce changes in EEG recording, more profoundly exhibited after administration of enalaprilat. PMID- 11208360 TI - Antitumor effect of electrochemical therapy on transplantable mouse cancers. AB - The aim of our study was to assess the antitumor effect of electrochemical therapy (ECT) in the mice bearing advanced transplantable tumours. Mouse mammary cancer 16/C (group 1) and fibrosarcoma F69-3 (group 2) were transplanted subcutaneously (s.c.) into the C3H or BALB/c mice, respectively. Twenty animals in each group bearing measurable s.c. tumours were randomly divided into two subgroups (experimental and control). Two electrodes were inserted into tumours and low level direct current (6-7 V, 5-21 mA) was passed. The animals were observed and tumors were measured twice a week. The animals were sacrificed and autopsied when the tumor diameter reached 2.0 cm. Two animals of each group (experimental and control) were sacrificed for histopathological tumor examination on the 1st and 6th day after ECT. A significant inhibition of tumor growth in mice subjected to ECT was observed, both in those with s.c. growing mammary cancer and with fibrosarcoma. This inhibition was associated with marked prolongation of survival time of ECT-treated mice. It appeared that the mice with mammary cancers were more susceptible to ECT therapy than those with growing s.c. fibrosarcoma. The histopathological studies of tumor specimens from ECT-treated mice showed extensive foci of necrosis with shrinkage of cell nuclei deprived of chromatin. In conclusion, the treatment which inhibits the growth of experimental mammary and fibrosarcoma tumors was demonstrated. However, in no mice complete regression of tumours was observed. PMID- 11208361 TI - Insertion/deletion polymorphism in the angiotensin-converting enzyme gene in myocardial infarction survivors. AB - INTRODUCTION: Insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene influenced the plasma concentration of the ACE, and is D allele have been repetitively suggested as a risk factor for myocardial infarction (MI). MATERIAL AND METHODS: Two hundert thirty six male myocardial infarction survivors under 65 years and with body mass index and total plasma cholesterol levels under 95% of the Czech population were included in the study. As control group, 302 male controls (1% randomly selected group from the Czech population) were genotyped. I/D polymorphism in the ACE gene was determined using polymerase chain reaction. RESULTS: The prevalence of the I/I, I/D and D/D genotypes was 0.218, 0.494 and 0.288, in the control group, and 0.178, 0.538 and 0.284, in the myocardial survivors, respectively. The male Czech population has the similar frequency of insertion and deletion alleles compared to other Caucasian populations. The frequencies of the alleles and genotypes of the ACE gene did not differ significantly between MI survivors and a control sample of the Czech population. CONCLUSION: It was shown that the I/D polymorphism in the gene for ACE is not a genetic risk factor for myocardial infarction in the Czech population. PMID- 11208362 TI - Plasma HDL-cholesterol has an effect on nitric oxide production and arachidonic acid metabolism in the platelet membranes of coronary heart disease patients without LDL-hypercholesterolemia. AB - AIM: To evaluate nitric oxide (NO) production and [3H]arachidonic acid (AA) incorporation into platelet membranes of coronary artery disease (CAD) patients with/without HDL-hypocholesterolemia. MATERIAL: 16 healthy controls (C), 14 CAD patients with plasma HDL-hypocholesterolemia (nCAD) and 14--without HDL hypocholesterolemia (nCAD). All subjects were without peripheral vascular disease and hypertension. The groups were matched for age, sex, BMI. The diagnosis of CAD was substantiated by coronary angiography. METHODS: Nitric oxide end products xNO (NO2- plus NO3-) levels in the platelet membranes were measured using anion exchange chromatography. [3H]AA release from labelled platelets was studied by the method of Neufeld and Majerus; radioactivity was measured by liquid scintillation counting. Levels of plasma HDL-cholesterol (HDL-Ch) and triglycerides were enzymatically determined. RESULTS: Significant increase (mean +/- SD; Mann-Whitney U test) of [3H]AA incorporation into platelet membrane phospholipids was noted in CAD patients in comparison with healthy subjects (p < 0.001). A correlation (multiple regression analysis) was established between HDL C level and [3H]AA (r = -0.58, p < 0.05, n = 28); and between HDL-Ch and NOx levels (r = 0.76, p < 0.05, n = 28) in CAD patients. CAD patients had lower NOx than healthy subjects (p < 0.0001), NOx was lower in the group with decreased HDL Ch concentration (wCAD 36 +/- 5 vs. nCAD 42.3 +/- 6 mumol/mg, p < 0.002). CONCLUSIONS: CAD patients show decreased ability to produce platelet-derived NO that leads to higher platelet sensitivity to aggregating stimuli. Decreased plasma HDL-Ch may affect AA metabolism and NO production in the platelet membranes of CAD patients without LDL-hypercholesterolemia. PMID- 11208363 TI - High-dose anthracyclines in the treatment of advanced primitive neuroectodermal tumors in adults--a single institution experience. AB - Primitive neuroectodermal tumors (PNET) are rare malignancies of presumed neural crest origin, most often presenting as bone or soft tissue masses in the trunk or axial skeleton, in children and young adults. Treatment of advanced PNET in adults is not clearly defined in the literature. Data concerning dose-intensive chemotherapy regimens for poor-risk patients with those tumors are sparse, due to rarity of PNET in adults, their diverse presentation, the variable treatment procedures applied and the absence of direct comparisons. On the other hand, the role of anthracyclines in the treatment of advanced soft tissue sarcomas is well known and substantial. Six advanced PNET patients were treated at the Institute for Oncology and Radiology of Serbia, during last five years, with high-doses of doxorubicin or epidoxorubicin combined with cisplatin. The paper reviews each of our patients, discussing how does chemotherapy influence the outcome in these patients, in context of the feasibility of high-doses of anthracyclines in advanced settings. High dose anthracyclines (epidoxorubicin 150 mg/m2) in combination with cisplatin 120 mg/m2 induced a complete response lasting for 63+ months in a patient with desmoplastic medulloblastoma of the cerebellum metastatic to bones and bone marrow. The same treatment but with the epidoxorubicin dose of 180 mg/m2 induced a complete response in a patient with olfactory neuroblastoma. Administration of high dose Doxorubicin (75 mg/m2) seems feasible in association with irradiation treatment in patients with extraosseal Ewing sarcoma/PNET but the place of high dose chemotherapy within this setting remains to be determined. PMID- 11208364 TI - Antenatal care: some characteristics of the booking visit in a major teaching hospital in the developing world. AB - BACKGROUND: The first (booking) visit is a very important component of antenatal care as service providers use the occasion to collect basic medical information that will form the basis to care for the patient throughout pregnancy. The study was undertaken to establish the socio-demographic characteristics of the patients booking at the UBTH, and determine areas where changes could be made to improve service uptake. MATERIAL AND METHODS: Between the months of February and August 1998, 378 consecutive pregnant women initiating antenatal care were interviewed using a structured questionnaire. RESULTS: The majorities (52.1%) of the patients were middle class, while 87.5% have a secondary or tertiary education. The mean age of the mothers was 29.7 years, and a mean parity of 1.3. Primigravidae constituted 32.0% of the patients; the number of mothers booking declined with increasing parity. The mean gestational age at booking was 23.7 weeks. The sixth month was the peak period for the initiation of antenatal care. The decision to attend UBTH for antenatal care was taken by the husband alone in 52% of the cases. Late booking because of ignorance and financial constraints was observed in 41.5% and 25% of the patients respectively. CONCLUSION: Patients attending UBTH are educated and of low parity. Initiation of antenatal care is late due to ignorance and financial constraints. Male dominance influences patients' adequate utilisation of antenatal services. Provision for the expectant fathers to attend maternity care activities will improve service uptake. PMID- 11208366 TI - Correlation between Helicobacter pylori infection and food allergy in chronic gastritis. AB - The purpose of this study was to evaluate the intensity of gastric inflammatory changes in atopic patients infected with H. pylori, and to find out whether a long-term exposure to a sensitizing allergen intensified the acuteness of inflammatory changes. The examinations were performed on patients with atopic diathesis who suffered from dyspepsia and gastralgia. The examined group included 72 women between 16 and 57 years of age (mean age: 36.5 years) and 38 men from 16 to 60 years of age (mean age: 34.4 years). The control group included 40 patients with no traits of atopy (13 men and 27 women between 18 and 56 years old, mean age: 34.8 years) with chronic gastritis confirmed by endoscopic and histopathological tests. All patients were subjected to endoscopy of the upper alimentary tract. Biopsy specimens were taken for histopathological analyses. They were stained with eosin and hematoxylin (the H&E method), and with a modified Giemsa method. The evaluation included the presence of chronic inflammation of gastric mucosa, its activity and intensity. The presence of H. pylori colonization was determined with the use of histopathological method of staining. Significant differences were found concerning inflammation intensity in atopic patients additionally infected with H. pylori, in comparison with the group of patients with food allergy without bacterial colonization. The differences were found during the evaluation of mucosa of both the prepyloric area and body of the stomach (p < 0.001). Moreover, statistically significant differences were found in the inflammation intensity between the examined group and the control group with no symptoms of allergy. In atopic patients infected with Helicobacter pylori, a long-term exposure to food allergens increases the intensity of gastric mucosa inflammation. PMID- 11208365 TI - Angiotensin II type 1 receptor gene A1166C polymorphism is associated with the increased risk of pregnancy-induced hypertension. AB - OBJECTIVE: The aim of our study was to evaluate the relation of parental history of hypertension to the development of PIH, and to assess the potential role of plausible candidate loci in the susceptibility to PIH. STUDY DESIGN: Five polymorphisms: ACE gene I/D and Pst1 RFLP polymorphism, AGT gene M235T polymorphism, AGTR1 gene A1166C polymorphism, and chymase gene CMA/B polymorphism were studied in 126 women suffering from PIH in comparison with 150 healthy pregnant women. Genotyping was performed using methods based on polymerase chain reaction. RESULTS: Among the PIH patients, positive parental history of hypertension (hypertension in both parents, in mother alone or in father alone) was significantly more frequent than in healthy pregnant women. Having a hypertensive father or mother statistically significantly increased the risk of PIH (odds ratio 4.34, 95% CI, 1.86-10.13, and 2.33, 95% CI, 1.29-4.12 respectively). CC genotype was significantly more frequent in women with PIH as compared with healthy controls and the C allele frequency was also significantly higher among the cases compared to controls. Having a CC genotype increased the risk of development of PIH 2.74 times (95% CI, 1.08-6.97). We observed no significant differences in genotype distributions or the allele frequencies of other examined polymorphisms. CONCLUSION: On the basis of the results of our study, we may suggest that AGTR1 gene A1166C polymorphism may predispose women to the development of PIH. It seems that ACE gene I/D and Pst1 RFLP polymorphism, AGT gene M235T polymorphism, and finally chymase gene CMA/B polymorphism do not play any significant role in the pathogenesis of PIH in Caucasian women. PMID- 11208368 TI - Various types of cholestatic jaundice in infants--causes and diagnostic problems. AB - The purpose of this review was to evaluate possible differentiation between various causes of different types of cholestatic jaundice in children. Analyses were performed in 33 infants from 3 weeks to 3.5 years old with symptoms of cholestatic jaundice. The most frequent causes of cholestasis were congenital atresia of extrahepatic bile ducts (30%) and the CMV infection (20%). On the basis of the performed examinations it should be concluded that in order to differentiate between the causes of cholestatic jaundice it is necessary to do a series of tests as there is no specific diagnostic method which would be effective. PMID- 11208369 TI - Multisensory principle of heart rate regulation. AB - We analyzed metabolic parameters during exercise in two groups of patients with implanted dual sensor VVIR. The first group was comprised of 14 patients (mean age 37.7 years) with implanted Topaz pacemakers and the second of 9 patients with a Legend Plus pacemaker (mean age 44.7 years). A control group consisted of 54 healthy individuals (mean age 40.4 years). Testing was performed on treadmill, using a stepwise staircase loading CAEP protocol. The following directly measured and mathematically calculated parameters we used in assessing the metabolic impact of pacemaker function: minute ventilation (MV), MV/body surface, MV/body mass unit, oxygen consumption, oxygen consumption/body surface, oxygen consumption/heart rate (oxygen pulse), oxygen consumption/body mass unit, carbon dioxide production, respiratory index. For the majority of the observed parameters statistically significant difference was not found between the control group and the patients with dual sensor nor single sensor controlled rate response. However, oxygen pulse showed a statistically significant difference when comparing the group with single sensor controlled rate response with dual sensor controlled rate response as well as to the control group (p < 0.05). Also, the time of reaching the anaerobic threshold, as well as the duration of the exercise test were significantly longer in dual sensor guided rate. Since these pacemakers are particularly aimed at a population of still active patients, this finding confirms their contribution to the better quality of life and justifies their use in these patients. PMID- 11208367 TI - Levels of serum total cholesterol and LDL-cholesterol in patients with major depression in acute period and remission. AB - The aim of the study was to determine the level of total cholesterol and LDL cholesterol in blood samples taken from 102 patients with recurrent major depression (according to DSM-IV). The analysis was performed during the acute period of major depression in 3 subgroups: with and without suicidal ideation (S+, S-), and after suicidal attempts (AS), and during remission of depressive symptoms. Putative correlations between the level of total cholesterol and severity of depressive symptoms and between total serum cholesterol and LDL cholesterol and suicidal risk were evaluated. The patients did not suffer from any additional disorders, factors such as specific diet or pharmacotherapy, which could influence the levels of lipids, were absent. The subgroups were identified using clinical evaluation, medical records and Hamilton Depression Rating Scale- HAMD-S as well as a subscale of MMPI-DMS. Biochemical analyses were performed twice in all patients, in the acute period, before pharmacotherapy and after effective pharmacotherapy, in remission. The following parameters were evaluated: total serum cholesterol and LDL-cholesterol, T3, T4, TSH, ALT, AST, proteinogram. In all depressed patients with acute depression symptoms, low levels of total cholesterol and LDL-cholesterol were shown. The level of total cholesterol 160 mg/dl or less and the level of LDL-cholesterol 100 mg/dl or less were observed in persons with suicidal behavior only (S+ and AS). Low total cholesterol and LDL cholesterol levels in persons in the acute period of major depression provided a useful parameter of suicide risk. A significant statistical correlation between the low level of total cholesterol and suicidal ideation was also found (r = 0.82, p < 0.05) as well as between the low level of serum total cholesterol and severity of depression, as evaluated by HAMD-S (r = 0.27, p < 0.05). During the remission of depressive symptoms, total cholesterol level and LDL-cholesterol increased significantly (p < 0.05) but a significant difference (p < 0.05) between subgroups (S-, S+, AS) were still observed. Low total cholesterol and LDL cholesterol levels in remission in persons with the diagnosis of recurrent major depression may help to estimate the risk of suicidal behavior in the next depressive disorder. Possibly, low level of serum total cholesterol is a stable feature in some persons with recurrent major depression, probably dependent on their predisposition to autoaggression and presence of depressive disorder. PMID- 11208370 TI - General anaesthesia for laparascopic adrenalectomy. AB - Surgical treatment of adrenal disorders is increasingly performed under laparascopic approach. Both pneumoperitoneum and adrenal tumour manipulation may induce haemodynamic variations. The aim of this study was to compare the inhalational and intravenous anaesthetic management for laparascopic adrenalectomy. Between 1977 and 1999 there were performed 28 laparascopic adrenalectomies. At patients with functioning adenoma and hypertension the anaesthesia was maintained with isoflurane in 8 cases and sevoflurane in 6 cases, et 14 patients with non-functioning adrenal masses with propofol and fentanyl (TIVA). In addition to the circulatory and respiratory monitoring there were made serial laboratory determinations (acid-base state, serum potassium, blood glucose) during the operation. On the basis of measured parameters isoflurane and sevoflurane anaesthesia proved to be favourable in case of functioning adrenal adenoma and TIVA with propofol and fentanyl in case of non-functioning adenoma. PMID- 11208371 TI - Effect of surgical technique in subtotal and bilateral thyroidectomy on risk of postoperative parathyroid insufficiency development--our experience. AB - One of the postoperative complications after strumectomy is hypoparathyroidism. Therefore, the purpose of our study was to evaluate the effect of the surgical technique on the development of parathyroid gland insufficiency in our group of patients. Subtotal, bilateral strumectomies were performed according to Rothmund's suggestions. Randomized controlled trial was performed in two groups. In the first group of 19 patients, main trunk of the inferior thyroid artery was ligated and in the second one consisting of 18 patients, only the branches of this artery were ligated. Total calcium and PTH levels were evaluated pre- and postoperatively. Based on the biochemical and clinical data, no statistically significant differences in the development of postoperative hypoparathyroidism in relation to performed surgical techniques were observed. PMID- 11208372 TI - Evaluation of selected cytokines and mononuclear cell infiltration in gastric mucosa of children with food allergy. AB - The authors performed simultaneous evaluation of histological changes in gastric and duodenal mucosa, phenotypic evaluation of mononuclear cells infiltration and the levels of selected cytokines of gastric mucosa in children with diagnosed food allergy. It was determined that IL-4, IL-5, IL-10 and TNF-alpha were produced locally within alimentary tract mucosa; they may play pathogenic role in food hypersensitivity in children. Increase in the number of T lymphocytes (CD3+, CD8+) and B lymphocytes (CD20+) as well as mastocytes with positive reaction to Mast Cell Tryptase-Mastocyte antibody was also observed in gastric and duodenal mucosa of these patients. PMID- 11208373 TI - Increased trend of type 1 diabetes mellitus in children's population (0-14 years) in Upper Silesia region (Poland). AB - THE PURPOSE OF THE STUDY was to provide current and reliable information about trends in the incidence rates of Type 1 Diabetes in the Upper Silesia region in children aged 0-15 years in the period of 9 years. RESULTS: Incidence ratio in the examined population increased from 4.71 in 1989 up to 10.16/100,000/year in 1997. In the analysed group no significant statistical differences dependent on sex were found. During the examined period, the incidence ratio has increased significantly. It was observed that the extent of change varied in different age groups. The youngest children (0-4 years old) showed the greatest increase of the incidence ratio from 1.09/10(5) in 1989 up to 6.75/10(5) in 1997. The highest incidence ratio was observed in the group of 10-14 year-olds. CONCLUSIONS: In the examined period dramatic increase (more than 200%) of the incidence ratio of type 1 diabetes was reported in the children's population (0-14 year-olds) in Upper Silesia. The fastest increase in this ratio was established in the group of youngest children (0-4 years old). PMID- 11208374 TI - Interstitial 6q duplication in an adult male without growth delay or severe mental retardation. AB - We report on a 28 year-old male with peculiar facies, distal joint contractures and other multiple congenital anomalies. Cytogenetic analysis by G banding revealed a distal tandem interstitial duplication of the long arm of chromosome q6, dup.(6)(6q24.2-->q26). This chromosome abnormality was confirmed by fluorescence in situ hybridization with total chromosome 6 painting. This is probably the second documented case of 6q duplication without growth retardation or severe psychomotor retardation. The clinical findings in our patient are similar to that of whistling face syndrome (WFS) and, in fact, he was diagnosed with WFS as a child. The literature were reviewed and the phenotypic features of this patient were compared with those previously reported for both duplication 6q and whistling face syndromes. There is a significant overlap between the phenotypes of these two syndromes. Careful evaluation of the terminal end of the 6q in cases suggestive of WFS might be warranted. PMID- 11208375 TI - Recurrent autoimmune LKM hepatitis with multiple relapses. AB - We describe three females who since childhood and puberty have presented with several relapsing episodes of acute or chronic LKM positive hepatitis. Many episodes resolved spontaneously with recovery of normal liver function, although treatment with steroids, steroids/azathioprine was used at occasions. No clear pattern of precipitating factors has emerged though in some cases possible temporal relationship of episodes to menarche, oral contraceptives use or pregnancy has suggested a role for female sex hormones. We discuss briefly the possible mechanisms of LKM positive hepatitis, particularly in terms of drugs as possible trigger factors. PMID- 11208376 TI - Early symptoms of Duchenne muscular dystrophy--description of cases of an 18 month-old and an 8-year-old patient. AB - The paper presents the description of Duchenne progressive muscular dystrophy in an 18-month-old and an 8-year-old boy. The diagnosis was established on the basis of clinical symptoms, such as impaired motor development, hypertrophy of leg muscles, difficulty in walking; elevated serum phosphocreatine kinase activity and pathologic electromyographic recordings. The authors emphasize that the disease is characterized by increased activity of such enzymes as: alanine and aspartate aminotransferases, lactate dehydrogenase and aldolase--observed as early as in the first weeks of life, with normal gammaglutamyltranspeptidase activity suggests progressive muscular dystrophy and makes it possible to establish early diagnosis. Early diagnosis of the disease allows to start rehabilitation earlier, to select an appropriate type of anesthesia in case of surgical treatment and to advise parents within the framework of genetic counseling. PMID- 11208378 TI - Perifolliculitis capitis abscedens et suffodiens--a case report. AB - Perifolliculitis capitis abscedens et suffodiens is a rare suppurative disease of the scalp of unknown aetiology. The treatment is usually difficult and often disappointing. In the case presented in the current work, the remission was achieved with nine-month isotretinoin treatment. PMID- 11208377 TI - Bleeding from alimentary tract in pseudo Zollinger-Ellison syndrome. AB - The report describes a case of a four-month-old infant, who developed acute gastric ulcer while being hospitalised because of pneumonia. One year's observation of the patient, additional tests, especially gastroscopy with histopathological evaluation of biopsy specimen, determination of gastrin level in blood serum, and therapy analysis allow to establish a diagnosis of pseudo Zollinger-Ellison syndrome. PMID- 11208379 TI - Blood cultures evaluation by gas chromatography of volatile fatty acids. AB - The volatile fatty acid profiles were determined by a simple gas chromatographic method in 375 microbiologically positive and negative blood cultures. Aerobic bacteria yielded profiles with low content of acids, some of which were chromatographically negative. Anaerobic bacteria produced more acids and more distinctive profiles. The method makes it possible to confirm the microbiological findings and to select the blood cultures containing anaerobic bacteria within 30 minutes. PMID- 11208380 TI - Doppler examinations in the prognosis of birth status of the newborn. AB - AIM OF THE STUDY: Determination of correlation between Doppler parameters in the evaluation of fetal state and biochemical and clinical determinants of birth status of the newborn. MATERIAL: 30 full-term pregnancies. METHODS: Doppler parameters were determined in maternal vessels (uterine and arcuate arteries), fetal vessels (middle cerebral arteries, renal artery and descending aorta) and in umbilical arteries and veins. Levels of uric acid, xanthine and hypoxanthine, which reflect oxygen deficiency, were assessed in amniotic fluid by means of HPLC method. Furthermore, clinical condition of a newborn (rating according to the Apgar scoring system), pH-metry and gasometry in umbilical blood were assessed. RESULTS: Significant correlation between determinants of fetal and neonatal condition and Doppler parameters were determined, that is: between uric acid concentration and blood flow in fetal cerebral arteries, between base excess, pH and blood flow in umbilical vessels, between clinical examination of birth status of the newborn and renal and arcuate arterial flow and between pO2 and S/D ratio in renal artery. CONCLUSIONS: On the basis of this correlation, the following conclusions were drawn: Doppler examinations are highly useful in the prediction of birth status of the newborn if the specific conditions and appropriate range of the examination are maintained, i.e.: 1) examination must be multivascular, 2) it should involve cerebral artery, parenchymal resistance vessels (for example renal artery), umbilical artery and vein, intramural uterine vessels (for example arcuate or spiral artery), 3) among blood flow parameters not only standard indices (S/D, RI, PI), but also arterial blood flow waves velocity, specific flow and transverse section field should be considered. PMID- 11208381 TI - Accuracy of t-PA, u-PA, PAI-1 and PAI-2 estimation in human bile by ELISA kits. AB - The aim of this study was to establish the accuracy of determination of fibrinolytic proteins in human bile using commercial kits. MATERIAL AND METHOD: Gall bladder bile was obtained from patient undergoing laparoscopic cholecystectomy. The concentrations of tissue plasminogen activator (tPA), urokinase (uPA) and plasminogen activator inhibitor-1 (PAI-1) and inhibitor-2 (PAI-2) in bile were measured by enzyme linked immunoassay. Afterwards we conducted so called 'recovery test'. RESULTS: Recovery percents of t-PA, u-PA, PAI-1, PAI 2 were very high i.e. 91.94, 94.07, 93.95, 91.2. We concluded that human fibrinolytic proteins in bile could be detected very accurately using commercial kits. PMID- 11208382 TI - Toxicity of commonly used laxatives. AB - Laxatives have a particularly marked abuse potential. Since they are available without prescription, physicians have no influence whatsoever on frequency of intake and dosage. The stimulant laxatives are preferentially abused since they are particularly cheap and the nature of their effect makes them appear suitable to users for non-intended purposes; advertising sometimes reinforces such impressions. Stimulants of plant and chemical origin can certainly be regarded as aggressive chemical substances that are pharmacologically active. Available data suggest that it would be advisable to bring the use of these substances under medical supervision since their widespread abuse and the associated risks can only be substantially reduced by such action. This review summarises toxicological data of stimulant laxatives and other freely available but more safe compounds such as lactulose. PMID- 11208383 TI - Comparative morphology of the hepatic and coronary artery walls. Part III. The insignificance of medial morphologic features in the determination of an autopsied unidentified subjects age. AB - Since hepatic arteries are free of atherosclerosis any possible wall structure change may be attributed to age. We determined the media of hepatic and coronary arteries in view of this assumption. We measured its thickness and myocytic density (per 1 mm2 of cross-section) from specimens collected from autopsied subjects, aged up to 90 years. The media gradually thickens with age, although values noted during particular decades remain statistically insignificant. The myocytic density (in 1 mm2) was almost constant throughout life. The latter observation is incompatible, in comparison with data reported by other authors (diminution was expected). PMID- 11208384 TI - Application of ursodeoxycholic acid (UDCA) in the therapy of liver and biliary duct diseases in children. AB - The paper discusses the experience accumulated so far in the field of application of ursodeoxycholic acid (UDCA) in selected disorders of the liver and biliary ducts in the developmental age population. In the aforementioned diseases, chronic administration of UDCA is safe, reduces the clinical symptoms, improves the biochemical parameters, and even the histopathologic picture of the affected organ. Such a therapy should be instituted in order to improve the quality of life, reduce the incidence of complications and postpone the transplantation of the liver till the time the child is older. PMID- 11208385 TI - Glutamate transport is downregulated in the cerebral cortex of alcohol-preferring rats. AB - INTRODUCTION: Ethanol (EtOH) affects glutamatergic neurotransmission and this may underlie craving in alcoholics. The present study aimed to further elucidate the EtOH-induced modulation of glutamatergic neurotransmission in a model for alcoholism: the alcohol-preferring cAA rat. MATERIAL AND METHODS: Glutamate transporter binding and function was assessed in membrane and synaptosomal preparations from the cerebral cortex of alcohol-preferring cAA rats and alcohol naive cAA rats. RESULTS: [3H]L-glutamate transport activity (Vmax) was 699 pmol.min-1.mg-1 in alcohol-naive cAA rats and 487 pmol.min-1.mg-1 in alcohol preferring cAA rats. The specific binding sites (Bmax) for [3H]D-aspartate were markedly decreased in alcohol-preferring cAA rats (2059 pmol/mg) as compared to alcohol-naive cAA rats (4275 pmol/mg). CONCLUSIONS: We hypothesize that the reduced density and function of glutamate transporter sites in alcohol-preferring cAA rats may represent an adaptive mechanism in order to counteract suppressed glutamatergic neurotransmission during chronic EtOH exposure. PMID- 11208386 TI - Formation of the D-loop structure complexes between DNA and oligonucleotides and affinity modification of DNA by chemically reactive derivatives of oligonucleotides lead to the recombination. AB - INTRODUCTION: Affinity modification of DNA by chemically reactive derivatives of complementary oligonucleotides (ODNs) and antisense ODNs has shown an application for the inhibition of gene expression and the growth of viruses and parasites in high organisms. Unfortunately, the rapid advancement of antisense therapeutic approaches is not parallel to the investigation of possible consequences of antisense and gene-directed ODNs on genetic material of the cells being treated. Here we tried for the first time to estimate a possible genetic impact of antisense ODNs and their chemically reactive derivatives on the cells using bacteria and the plasmid DNA. MATERIAL AND METHODS: Recombination of direct repeats, induced by the formation of reversible complexes of plasmid DNA with complementary ODNs and after covalent binding of the alkylating derivative of the ODNs with DNA, has been investigated. For this purpose, a polylinker sequence flanked by 165 bp direct repeats was inserted within the tet gene of pBR 327. This plasmid was used to construct DNA containing AT- and GC-rich sequences placed in the central region of the polylinker. RESULTS: Transformation of E. coli cells with the plasmids (and with mixtures of the plasmids with d(pN)17 complementary to the AT- and GC-rich sequences) did not produce deletions. After modification of plasmids with alkylating derivatives of d(pN)17, the deletion of the polylinker DNA region (recombination) revealed the restoration of the tet gene function. The same effect was found at the cell transformations with the D loop complex of the plasmids with ODNs, but the frequency of the transformants was about 1.5-2 times lower. The data obtained demonstrate that the complexes of DNA with complementary ODNs and the modification of the plasmids by reactive ODN derivatives result in induction of the recombination process and in loss of genetic material. PMID- 11208387 TI - BsmI vitamin D receptor polymorphism and pathogenesis of parathyroid adenoma. AB - INTRODUCTION: The role of vitamin D receptor (VDR) gene polymorphism in the pathogenesis of hyperparathyrodism is not clear yet. The aim of this study was to examine the role of BsmI VDR gene polymorphism in patients with primary hyperparathyrodism (PHP) secondary to adenomas. MATERIAL AND METHODS: Fifty-two postmenopausal women with PHP, mean age 64.5 years, were compared with a normal age-matched female population (n = 81). RESULTS: Distribution of BsmI polymorphism in PHP group was: Bb 54% (28/52); BB 21% (11/52); bb 25% (13/52). In the control group, the distribution in PHP group as follows: Bb 49% (40/81); BB 16% (13/81); bb 35% (28/81). No statistical differences were found between the two groups. In the PHP group, no statistical associations were found between different allelic distribution and age, creatinine, hematocrit, phosphorus, alkaline phosphatase (ALP), total calcium, serum parathyroid hormone (PTH), or gland weight. This data suggest that at least in this group, BsmI VDR gene polymorphism appears to be without relevance in clinical presentation and possibly tumorigenesis in PHP secondary to adenomas. PMID- 11208389 TI - Morphological changes of aortal smooth muscle cells exposed to calcitriol in culture. AB - INTRODUCTION: A number of observations suggest that vitamin D plays an important role in maintaining normal cardiovascular function, through its receptors in cardiac muscle or in aortal smooth muscle cells (SMCs). The purpose of this study was to determine the effect of vitamin D active metabolite--calcitriol [1,25(OH)2D3] on aortal SMCs. MATERIAL AND METHODS: The cells were isolated from the aortal media of newborn rats by enzymatic digestion and maintained for 6 weeks in primary culture. 1.2 microM of calcitriol was added to the medium every second day. RESULTS: Light microscopic investigations revealed that the control SMCs formed multilayer with characteristic 'hills and valleys'. Uniform cellular growth patterns were observed after calcitriol treatment. Ultrastructural studies indicated more rapid modulation of SMCs from the 'contractile' to the 'synthetic' phenotype following calcitriol treatment. Elastic fibers were more abundant in treated than in control cultures. The scanning electron microscope showed an increase of regular microvilli on the surface of SMCs. Morphometrical analysis of nuclei demonstrated phenotypic heterogeneity in populations of aortal SMCs. These results suggest that 1) calcitriol can induce changes in the phenotype and in the growth pattern of aortal SMCs, which may be associated with the onset or progression of the atherosclerosis process, 2) the basis of phenotypic changes is related to the stimulation of proliferative activity in these cells. PMID- 11208388 TI - Soluble TNF and IL-2 receptors in patients with breast cancer. AB - INTRODUCTION: Cytokines were shown both to enhance tumour growth and formation of metastases and to inhibit proliferation of tumour cells. TNF alpha may mediate apoptosis and necrosis of cancer cells, while the exact role of IL-2 remains to be elucidated. Plasma levels of TNF alpha and TNF and IL-2 soluble receptors (sTNF-R, sIL-2R) should thus be in some relation to some biological characteristics of the breast cancer. MATERIAL AND METHODS: Plasma levels of TNF alpha, sTNF-R I and II and sIL-2R were measured in 31 women with different stages of breast cancer both before the institution of therapy and after 3 months of the treatment. RESULTS: Plasma levels of both types of sTNF-Rs were higher in patients with breast cancer than in controls (sTNF-R I--2166.6 +/- 568.9 vs. 1121.3 +/- 260.6 pg/ml, p < 0.001, sTNF-R II--3792.8 +/- 958.9 vs. 1996.2 +/- 404.3 pg/ml, p < 0.001) with no significant difference between clinical stages. Plasma levels of both sTNF-R (0.871, p < 0.001) and sIL-2R tightly correlated with each other. Plasma levels of TNF alpha decreased after treatment (from 3.92 +/- 1.86 to 3.40 +/- 1.15 pg/ml, p < 0.01), but plasma levels of sTNF-Rs and sIL 2R were not influenced by the therapy. CONCLUSION: Plasma levels of soluble TNF receptors may thus serve as a non-specific marker of the untreated breast cancer. Their relation to other biologic characteristics of this tumour is not clear. It remains also to be clarified if the long-term treatment leads to the normalization of sTNF-Rs plasma levels. PMID- 11208390 TI - Effect of splenectomy on the morphology of haemolymph splenic nodes in Wistar rats. AB - MATERIAL AND METHODS: In 12 Wistar rats the gross and microscopic structure of haemolymph splenic nodes was assessed after splenectomy and the obtained results were compared with those in the control group. RESULTS: It was found that splenectomy leads to generalised morphological changes of the mentioned nodes, including, among other, their blanching, enlargement, filling with a greater number of morphotic elements and decreased count of erythrocytes and products of their disintegration. The splenic nodes demonstrated no regressive changes, typical of uniorgan nodes. The remaining abdominal non-haemolymph nodes in the rats showed no compensatory changes on gross examination after splenectomy. PMID- 11208391 TI - Zinc level in selected tissues of ethanol and morphine intoxicated mice. AB - INTRODUCTION: In this work we determined zinc level in the brain, heart, lungs, liver, kidneys, spleen and thigh muscle of the ethanol- and morphine-intoxicated mice. MATERIAL AND METHODS: The experiment was conducted on mice, which were divided into four groups of ten mice each. They were given ethanol intragastrically, morphine--intraperitoneally, and a combination of ethanol and morphine. The concentration of zinc was determined spectrophotometrically, using spectrophotometer Pye Unicam SP-192. RESULTS: The narcotic drugs affected zinc level and zinc distribution in the tested tissues. All the narcotic agents caused an increase in zinc concentration in blood serum and a decrease of this microelement in the brain. Ethanol intoxication caused a decrease of zinc level in all the tissues except the heart. Morphine- as well as morphine-and-ethanol intoxication, however, caused an increase or decrease of this microelement. PMID- 11208392 TI - Plasminogen activators (t-PA and u-PA) and plasminogen activators inhibitors (PAI 1 and PAI-2) in some myeloproliferative syndromes. AB - INTRODUCTION: Clinical observations and laboratory data indicate that patients with myeloproliferative syndrome (MPS) have hemostasis disorders that manifest with haemorrhagic diathesis or thrombotic disease. The role of fibrinolytic system is not clear in the pathomechanism of the disorders. In the study we aimed to evaluate fibrinolysis system in blood plasma of the patients with selected myeloproliferative syndromes on the basis of examinations of plasminogen activators (tissue--t-PA and urokinase-type--u-PA) and type 1 and type 2 plasminogen activator inhibitors (PAI-1 and PAI-2). MATERIAL AND METHODS: Forty two patients (F/M 28/14) aged 36-78 years (average age--54 years) were enrolled into the study. Among the patients were 20 individuals with chronic myeloid leukaemia (CML), 17 with essential thrombocytemia (ET) and 5 with myelofibrosis (MF) treated in Provincial Haematological Outpatient Clinic in Bydgoszcz. Forty healthy volunteers (F/M 30/10) aged 24-65 (average 53) were included in control group. In citrate venous blood, the following parameters were determined: concentrations of antigen t-PA, u-PA, PAI-1, PAI-2, concentration of plasmin alpha-2-antiplasmin complexes (PAP) determined with the use of ELISA technique, PAI-1 activity with amidolytic method, euglobulin lysis time (ELT) according to Kowarzyk-Buluk and fibrinogen/fibrin degradation products (FDP) concentration with the use of Merskey's method. RESULTS: Performed evaluations show that besides normal ELT elevated concentrations of FDP and PAP complexes occur in the blood of patients with myeloproliferative syndromes (MPS.). In studied myeloproliferative syndromes, high concentration of PAI-1 Ag and very low activity of PAI-1 were observed. In the patients with MPS intensified plasminogenesis and increased fibrin degradation were demonstrated. The role of granulocyte elastase is considered in activation of fibrinolysis system. PMID- 11208393 TI - Predictors of the efficacy of intravenous natural interferon-beta treatment in chronic hepatitis C. AB - INTRODUCTION: Several pretreatment factors have been reported to be useful in predicting patients with a high probability for a sustained response to IFN-alpha treatment, however, predictors of the efficacy of interferon-beta treatment in chronic hepatitis C have not been fully assessed. MATERIAL AND METHODS: To clarify this issue, a prospective study of 52 patients with chronic hepatitis C was conducted. Patients were treated with human natural interferon-beta by drip infusion at doses of 6 MU/day for 8 weeks. The following characteristics were compared between patients with sustained response (SR) and no response (NR): gender, age, source of HCV infection, mean pretreatment serum ALT levels, liver histology, pretreatment serum HCV-RNA levels and HCV genotype. RESULTS: Seventeen of 52 patients (32.7%) demonstrated SR. The proportion of patients with undetectable HCV-RNA levels determined by branched DNA assay (< 0.5 x 10(6) eq/ml) was higher in patients with SR than in those with NR (88.2% vs. 22.9%; p = 0.0001). Pretreatment HCV RNA levels determined by multicyclic reverse transcriptase polymerase chain reaction were lower in patients with SR than in those with NR (10(5.1 +/- 1.5) vs. 10(7.1 +/- 1.3) copies/ml; p = 0.0001). The rate of SR was higher in patients with genotype 2a or 2b than in genotype 1b (43.8% vs. 15.0%; p = 0.0382). Multivariate stepwise logistic regression analysis showed that a younger age and low pretreatment serum levels of HCV RNA were independent predictors of SR to treatment. This prospective study demonstrated that a younger age, low pretreatment viral load and HCV genotype 2a or 2b were factors influencing the SR to interferon-beta treatment, but a younger age and low pretreatment viral load were most important predictors of the efficacy of the treatment. PMID- 11208394 TI - Combination of diet, exercise and intermittent treatment of cimetidine on body weight and maintenance of weight loss. A 42 months follow-up study. AB - INTRODUCTION: The aim of the study was to investigate the long term effect of diet, exercise and intermittent treatment of cimetidine on body weight and maintenance of weight lost during treatment. MATERIAL AND METHODS: Fifty women and five men who had completed a 8 week randomized double-blind, placebo controlled trial of cimetidine for weight loss were invited to participate in an open, non-randomized follow-up study of 42 months. The study was designed to compare weight loss and/or weight gain in subjects who, dependent on their level of motivation, volunteered to participate in an intervention or non-intervention group. In the intervention group the subjects were treated with cimetidine for 8 weeks twice a year, followed a diet restriction and performed regular exercise. In the non-intervention group the subjects had no behavioral treatment. Twenty two subjects volunteered to participate in the intervention program whereas 33 subjects volunteered to participate in the non-intervention group. RESULTS: In the intervention group, non-significant reductions in body weight (1.9 +/- 5.5 kg), BMI (0.6 +/- 1.7 kg/m2), body fat% (1.7 +/- 2.9) and waist circumference (2.1 +/- 5.9 cm) were found. In the non-intervention group there was a significant increase in body weight (7.5 +/- 5.3 kg), BMI (2.6 +/- 1.8 kg/m2), body fat% (3.0 +/- 3.3) and waist circumference (6.7 +/- 5.1 cm). Among the group of subjects initially treated with cimetidine for 8 weeks and who followed a subsequent intervention of additional 42 months (n = 16), there was a 15.1% weight loss. Among the group initially treated with placebo for 8 weeks and who volunteered to participate in the non-intervention group (n = 22), there was a weight gain of 8.6%. In conclusion, the combination of diet restriction, regular exercise and intermittent treatment of cimetidine appears to have long term effects on body weight and maintenance of weight loss. PMID- 11208395 TI - Results of surgical treatment of retinal detachments complicated with proliferative vitreoretinopathies with the use of perfluropropane (C3F8) gas. AB - The aim of the current study is the efficiency assessment of C3F8 gas usage in posterior vitrectomies in patients having retinal detachment of different etiologies with presence of proliferative vitreoretinopathies and retinal tears. 34 patients have undergone posterior vitrectomy with the usage of perfluoropropane C3F8 gas for providing internal tamponade. Total attachment of retina has been attached in all 34 cases and C3F8 gas has been injected in each eye. The most frequent complications that have been revealed after the usage of C3F8 gas and their management are reflected in the article. Thus, we came to a conclusion that vitrectomy in combination with episcleral buckling, transvitreal drainage of subretinal liquid, diode endolaser coagulation of retina and internal tamponade with C3F8 gas is effective and pathogenetikally proved method for treatment of rhegmatogenous retinal detachments complicated with severe vitreoretinopathies. The achievement of perfect anatomical results depends on manifestation degree of proliferative vitreoretinopathy. This study was supported by grant of the Ministry of Health of Armenia. PMID- 11208396 TI - Detection of minor myocardial injury after successful percutaneous transluminal coronary angioplasty with or without stenting. AB - Cardiac troponins are sensitive and specific markers for the detection of minor myocardial injury. However, they have been rarely used to monitor myocardial injury after coronary stenting. The purpose of the study was to measure cardiac troponin I (cTnI) and cardiac troponin T (cTnT) levels after apparently successful percutaneous transluminal coronary angioplasty (PTCA) with or without coronary stenting and to compare their results with serum creatine kinase (CK) and its isoform, creatine kinase-MB (CKMB). CTnI and cTnT levels were compared with those of CK or CKMB in 50 consecutive patients with stable angina undergoing visually successful PTCA with stenting (n = 35) or without stenting (n = 15). Cardiac TnI, cTnT, CK and CKMB levels were measured before and 6, 24, and 48 hours after the procedures was performed. None of the patients had abnormal cTnI or cTnT levels, CK activity, or CKMB levels before the procedures. Moreover, no patient showed electrocardiographic evidence of myocardial infarction. 13 patients (26%) had abnormal peak values of one or more markers at 24 hours after coronary intervention. Troponin I was elevated in 10/35 patients after coronary stenting (29%) and in 2/15 patients after PTCA (13%) (P = 0.327). Troponin T was elevated in 6 patients (17%) and CKMB activity was elevated in 3 patients (9%) of the coronary stenting group. CTnI was more significant than CKMB (P = 0.023) in detecting minor myocardial injury. When compared with cTnI and CKMB, cTnT did not reach significance (P = 0.129 and 0.489, respectively). 5 out of the 13 patients with abnormal markers (38%) developed side branch occlusion after stenting. In conclusion, cTnI was a very sensitive marker in detecting minor myocardial injury after coronary angioplasty with or without stenting. The frequency of increased serum levels of cardiac troponins was higher in patients undergoing stent implantation than in those treated with angioplasty alone but did not reach significance. Side branch occlusion may have accounted for some, but not all, periprocedural minor myocardial injury in the stent group. PMID- 11208397 TI - Antioxidant defense in children with chronic viral hepatitis B and C. AB - INTRODUCTION: The aim of the study was estimation of antioxidant defence state in children with chronic viral hepatitis. MATERIAL AND METHODS: We examined 100 children with chronic viral hepatitis who have serological and molecular markers of HBV or HCV infection. In all patients catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in erythrocytes were assayed. RESULTS: We observed statistically significant decrease of CAT and SOD activities and increase of GSH-Px activity in children with chronic hepatitis B and C. CONCLUSIONS: Our data suggest the possibility of insufficiency of antioxidant barrier in children with chronic viral hepatitis. PMID- 11208398 TI - Estimation of antithyroid antibodies occurrence in children with coeliac disease. AB - INTRODUCTION: The coexistence of coeliac disease (CD) and the diseases of autoimmune origin is often discussed in literature. In this study the evaluation of antithyroid antibodies (antimicrosomal-TMA, anti-thyreoglobulin-ATG, thyroid peroxidase antibodies anti-TPO) occurrence against clinical and laboratory determinants of thyroid function is demonstrated in children with coeliac disease. MATERIAL AND METHODS: The study was conducted on 34 IgA-EmA positive children; control group consisted of 28 children with negative screening tests for coeliac disease. RESULTS: In both groups, the level of antithyroid antibodies (TMA, ATG, anti-TPO) and determinants of thyroid gland function (TSH, fT3, fT4) were evaluated; USG examination of thyroid gland was also performed. Elevated titres of antithyroid antibodies observed in children with coeliac disease (41.1%) in comparison to control group (3.56%) indicate the need for performing the screening tests for antithyroid antibodies in children with CD. PMID- 11208399 TI - Low doses of aprotinin in aortocoronary bypass surgery--advantages and disadvantages. AB - INTRODUCTION: Excessive blood loss, as a result of augmented postoperative drainage, is considered one of the most serious cardiosurgical complications. The compounding constitutive anemia seems particularly harmful for patients with coronary artery disease. Aprotinin (Trasylol), a non-specific serine protease inhibitor, is successfully used to reduce excessive postoperative bleeding in such patients. The aim of our study was to verify the hypothesis whether aprotinin used during cardiopulmonary bypass procedure affects hemostatic parameters, which might be crucial for the elevated risk of thromboembolic complications. MATERIAL AND METHODS: The group of 54 patients subjected to coronary artery surgical treatment included 30 patients, who were given intraoperatively 3 million KIU aprotinin each, and 24 subjects non-treated with aprotinin. Aliquots of blood were withdrawn at several time intervals, until the 5th day after the operation. Whole blood platelet activation and reactivity (the expressions of P-selectin and glycoprotein Ib) were monitored by means of flow cytometry. In addition, several plasma parameters, like PAI-1, t-PA, D-dimers, prothrombin fragment F1 + 2, fibrinogen, ATIII activity, troponin I and CK-MB, as well as platelet count were determined at each time point. RESULTS: In this study we confirmed the essential advantage of the use of aprotinin: both the postoperative blood drainage and the blood units to be transfused postoperatively to cardiosurgical patients were vastly reduced in the aprotinin-treated subjects. The enhanced overall frequency of perioperative myocardial infarction events was not attributed to this group of patients, nor the non Q-wave infarctions were observed more often in patients treated with aprotinin. In these patients, fibrinolysis parameters tended to be depressed (with increased PAI-1 dominating over elevated t-PA) on the first day after the operation, and no significant differences with regard to fibrinogen, prothrombin fragment F1 + 2, troponin I and platelet count. There was a continuous rise in D-dimers in all the postoperative patients, which lasted until the third day and tended to reach plateau at the 5th day after the operation. We failed to reveal the preventive effects of aprotinin on platelet function: both platelet activation and reactivity remained apparently unchanged. Overall, our results rather support the reasoning on the advantageous effects of low doses of aprotinin. The use of this inhibitor reduces the risk of postoperative undesirable bleeding and results in a decreased postoperative drainage and reduced transfused blood units. On the other hand, however, a higher incidence of perioperative Q-wave infarction in the aprotinin-treated patients, although purely apparent and not statistically significant, might question the unlimited safety of the use of aprotinin in cardiovascular operations. PMID- 11208400 TI - Postheparin serum lipolytic activity in psoriatic males. AB - INTRODUCTION: As numerous papers have presented many disturbances of blood lipid composition and changes in lipolytic enzyme activity, it was considered appropriate to investigate the postheparin lipolytic activity in serum of psoriatic males. The course of serum lipolytic process provoked by intravenous application of heparin was observed by measuring the concentration of the major substrates and products: triglycerides (TG), free fatty acids (FFA) and glycerol (G) before intravenous bolus of heparin 10 units per 1 kg b.w. and after 30 minutes. MATERIAL AND METHODS: The study group consisted of 30 psoriatic males with mean age 29.7 +/- 9.6 and mean BMI 24.2 +/- 3.3 and was compared with 35 healthy males with corresponding mean age and mean BMI. The release of glycerol and FFA and the reduction of TG concentrations following intravenous heparin were observed. RESULTS: Psoriatic sera demonstrated higher concentrations of triglycerides, glycerol and free fatty acids before and after the lipolysis compared with the controls. The course of postheparin lipolysis in psoriatic males seems to be changed as compared with the control group. PMID- 11208401 TI - Minimally invasive saphenous vein harvesting for coronary artery bypass grafting- comparison of three less invasive methods. AB - INTRODUCTION: Saphenous vein is routinely harvested using one or a few long continuous skin incisions. This method is associated with typical healing complications such as oedemas, pain, necrosis, what often restricts proper rehabilitation. An alternative minimally invasive techniques may decrease these complications. MATERIAL AND METHODS: This prospective randomised trial compared outcomes associated with saphenous vein harvested using three minimally invasive techniques versus a traditional longitudinal incision. RESULTS: In the less invasive group we observed statistically significant improvement in all estimated parameters of wound healing, oedemas and pain. We present also costs analysis between the groups. CONCLUSIONS: We conclude that less invasive techniques of saphenous vein harvesting may be alternatively introduced in coronary bypass surgery. PMID- 11208402 TI - 2-Chlorodeoxyadenosine treatment of Waldenstrom's macroglobulinemia--the analysis of own experience and the review of literature. AB - INTRODUCTION: The aim of the study was to evaluate the results of treatment of Waldenstrom's Macroglobulinemia with 2-chlorodeoxyadenosine. The evaluation was based on our own experience as well as on the data published previously in the literature. MATERIAL AND METHODS: 25 patients with Waldenstrom's Macroglobulinemia (MW) were treated with 2-chlorodeoxyadenosine (2-CdA) at the dose of 0.14 mg/kg b.w./day for five consecutive days as 2-hour intravenous infusions. Chemotherapy was repeated every 28 to 35 days. RESULTS: In one case (4%) a complete remission and in 15 patients (60%) a partial remission was achieved. In 6 patients (24%) stabilization of the disease was observed while in 3 patients (12%) progression was noted during the treatment. As a result of the therapy, the mean monoclonal protein concentration decreased from 28.7 g/l (range 5.5-62.5 g/l) to 16.7 g/l (range 0-62.9 g/l) and the mean hemoglobin concentration increased from 10.6 g/dl (range 6.9-13.4) to 12.4 g/dl (range 8.2 14.8 g/dl). CONCLUSION: Our own experience, as well as conclusions of other authors, confirm the effectiveness of 2-CdA in MW treatment. Both the results of treatment and intensity of side effects observed in our treatment group were comparable to those described in previous reports. PMID- 11208403 TI - Evaluation of taeniasis prevalence in the area supervised by the Provincial Sanitary-Epidemiological Unit in Szczecin between 1994 and 1998. AB - INTRODUCTION: The aim of the study was to investigate the prevalence of taeniasis in population supervised by the Provincial Sanitary-Epidemiological Unit in Szczecin between 1994 and 1998. MATERIAL AND METHODS: The prevalence of intestinal taeniasis in population of Szczecin Province was evaluated basing on data from the selection charts available in the Provincial and Field Sanitary Epidemiological Units between 1994 and 1998. The following parameters were analyzed: environment (urban, rural), sex and age groups of patients. Basing on these data the prevalence of taeniasis per 100,000 of citizens was calculated. The study presents also the prevalence of taeniasis according to the species. RESULTS: In the studied period 337 cases of infestation of tapeworms were registered. The incidence of taeniasis in the consecutive years tended to be decreasing. The incidence of taeniasis decreased from 10.33 cases per 100.000 of population in 1994 to 3.52/100.000 in 1998. The incidence rate was higher in urban residents than in rural residents. In the whole analyzed period 82% of cases were noted in patients aged 20-59; however, the highest incidence of taeniasis (30%) was observed in patients aged 40-49 years. Taenia saginata turned out to be the prevalent species. The percentage of unclassified taeniasis (Taenia species) was only 3.3% in the analyzed period of time. It is necessary to improve the accessibility of efficient health care units in the rural environment to make the evaluation of incidence of taeniasis reliable. CONCLUSIONS: Taeniasis, despite its lower prevalence in the consecutive years, is still an epidemiological problem. Better access to effective health care institutions in the rural area is extremely important for reliable evaluation of prevalence of tapeworm infestation. PMID- 11208404 TI - Impact of baseline level of 7-ketocholesterol on the rate of coronary reintervention in coronary artery disease patients--results of an observational study with questionnaire-based follow up. AB - INTRODUCTION: The aim of study was to assess the relation between plasma level of one of the oxysterols--7-ketocholesterol and angiographically evidenced coronary artery disease. MATERIAL AND METHODS: We measured plasma level of 7 ketocholesterol, malondialdehyde, total cholesterol, HDL cholesterol, triglycerides, erythrocyte activity of superoxide dismutase in 233 patients who previously underwent coronary angiography for diagnosis of coronary artery disease. The follow-up of patients (28 months) was done on basis of questionnaires sent out to them. RESULTS: We found that the subgroup of patients with 7-ketocholesterol above the median value (62 ng/mL) has higher rate of coronary reintervention (8/54 pts vs. 5/43 pts in 7-ketocholesterol below 62 ng/mL respectively, p = 0.284 Log-rank test). The finding was more pronounced, yet insignificant, in the subgroup of patients who underwent primary PTCA (6/19 pts vs. 2/20 pts, p = 0.1 Log-rank test). There were 3 patients in high 7 ketocholesterol subgroup who entered the study with previously undergone primary coronary intervention. There were not such patients in low 7-ketocholesterol subgroup. 4 deaths were observed in high 7-ketocholesterol subgroup, and one in low 7-ketocholesterol subgroup (they were predominantly not of cardiovascular origin). CONCLUSIONS: We failed to find a significant relation between 7 ketocholesterol and coronary artery disease, though there is a trend of such relation in patients who undergo PTCA, evidenced by a slightly higher number of repeated revascularizations among patients with high 7-ketocholesterol. The study indicates the areas of further studies with agents capable of lowering oxysterols and assessing also other end points. PMID- 11208405 TI - Endometrial progesterone and estradiol receptors in patients with recurrent early pregnancy loss of unknown etiology--preliminary report. AB - INTRODUCTION: It is not possible to identify the cause of the recurrent early pregnancy loss in approximately half of the cases, and different results have been reported according to estrogen (ER) and progesterone receptors (PR). The objective of this work was to evaluate the PR and ER levels in the endometrium of patients with recurrent early pregnancy loss, and to compare them with those of patients with proven fertility. MATERIAL AND METHODS: Endometrial receptors (R) for estrogen and progesterone as well as estradiol (E2) and progesterone (P) levels were determined in patients with recurrent early pregnancy loss, and compared with patients with proven fertility. RESULTS: The E2 and P levels, and the E2/P ratio did not show significant differences among the groups. Estrogen receptor in the cytoplasm and nucleus was lower in those with miscarriages, but without significant differences between the groups. However, the cytoplasmic PR was lower in those with pregnancy loss (p < 0.04), while nuclear PR was lower in the control group (p < 0.04). CONCLUSION: Maybe low PR levels can be the cause of early pregnancy loss of unknown etiology, but this deserves further investigation. PMID- 11208406 TI - What intervals in oral therapy of isosorbide dinitrate in various doses are sufficient to prevent nitrate tolerance? AB - INTRODUCTIONS: The organic nitrates are effective anti-anginal drugs during initial treatment, but their therapeutic value is compromised by the rapid development of tolerance during sustained therapy. The only widely accepted method of preventing tolerance is the use of intermittent administration, but without specifying to what extent the length of interval is dependent on type and dose of nitrate. The aim of this study was to evaluate how long periods free of nitrates are sufficient to prevent tolerance in long-term therapy with oral sustained-release isosorbide dinitrate (ISDN). MATERIAL AND METHODS: In a double blind study, 38 patients with stable angina, received ISDN: 40 mg, 80 mg and 120 mg or placebo in the first ingestion (1st) and in long-term therapy in four 7 day phases: 4-times-daily (4x), 3-times-daily (3x) with 12 h nitrate-free interval, twice-daily (2x) with 18 h interval and once-daily (1x). After 1st and on the last day of each long-term phases, exercise tests with the analysis of walking times: total, to angina and to ischaemia (WTI) were performed: preceding ingestion, 2 h and 6 h after. RESULTS: Six hours after 1st all doses WTI improved significantly in comparison to placebo (p < 0.0001): 40 mg by 52.5%, 80 mg by 66.0% and 120 mg by 58.4%. None of the ISDN doses improved significantly WTI in 4x phase; in 3x, only 40 mg by 12.1% (p < 0.05); in 2x, only 80 mg by 22.3% (p < 0.05) and in once-daily, 80 mg by 27.2% and 120 mg by 36.2% (p < 0.01). CONCLUSION: 12 h nitrate-free interval is sufficient in order to prevent tolerance in long-term treatment of sustained-release ISDN with 40 mg dose, 18 h with 80 mg and 24 h with 120 mg doses. PMID- 11208407 TI - Administration of clemastine--H1 histamine receptor blocker in the prevention of haemodynamic disorders after protamine sulfate administration in patients subjected to coronary artery bypass grafting in extracorporeal circulation. AB - INTRODUCTION: Adverse effects of protamine administration after CPB: fall in arterial blood pressure and pulmonary hypertension are still a source of problems. CPB and protamine administration are both accompanied by increased histamine levels in blood. The aim of this study was to examine if clemastine can accelerate the normalisation of arterial blood pressure during the protamine administration after CPB during CABG operations. MATERIAL AND METHODS: Fifty three patients subjected to CABG operations were studied. Control group (n = 27) did not receive clemastine, Clemastine group (n = 26) received 2 mg i.v. clemastine, before CPB. After CPB were completed, patients were given protamine (heparin to protamine ratio--1:1.5) within 7 minutes, through peripheral vein. Changes in arterial blood pressure from the beginning of protamine administration to 2.5, 5, 7.5, 10, 15, and 30 minutes thereafter, as well as heart rate, CVP, doses of inotropic drugs and vasodilators were compared between the groups. RESULTS: No difference in heart rate, CVP, doses of inotropic drugs and vasodilators between the group was noted. An increase in arterial blood pressure 5, 7.5, 10, and 15 minutes after the beginning of the protamine administration were greater in clemastine group than in control group. Groups were comparable with regard to surgical procedures and doses of anaesthetic drugs. It is now known that protamine exerts a negative effect on cardiac contractility either through a decrease in coronary perfusion pressure (vasodilatation), or through a direct toxic effect on cardiac muscle. The administration of clemastine before CPB can reduce peripheral vasodilatation and capillary leak related to histamine release during CPB. In the clemastine group, faster increase in arterial blood pressure toward a physiologic range was observed. We conclude that administration of clemastine is connected with the normalization of ABP during and after protamine reversal of heparin coagulation during CABG operations. PMID- 11208408 TI - Additional case of Keipert syndrome and review of the literature. AB - We report on a 7-year-old boy with unusual facial features, severe bilateral sensorineural hearing loss, and broad terminal phalanges. These findings are similar to those described by Keipert et al. in two brothers and by Balci and Dagli in two other male siblings. Our patient has, in addition, developmental delay and abnormal behaviour. To the best of our knowledge, this is only the third report of Keipert syndrome. PMID- 11208409 TI - Case report of schwannoma of the rectum--clinical and pathological contribution. AB - The case of benign schwannoma of the rectum primarily misdiagnosed as myogenic (neurogenic?) sarcoma is presented. A large tumor of 8 cm in diameter of the anterior rectal wall was removed with wide margins and an artificial anus was constructed. During 12 years of follow-up neither local recurrence nor distant metastases were observed. The patient is still alive and free of the disease. For that reason a surgery specimen of the tumor was pathologically reanalyzed and it showed features of type Antoni A and B tissues. These findings, together with strong reactivity for S-100 protein, Vimentin and negative for Actin supported the diagnosis of benign schwannoma. Because the localization of the tumor in the rectum is extremely rare, clinical and pathological features are presented and discussed. PMID- 11208410 TI - Cornual pregnancy--a case report. AB - Ectopic pregnancy is a rare phenomenon in mammals. The most common localization is an oviduct, ovary and abdominal cavity. Confirmation of the ectopic pregnancy is always a difficult medical problem. The diagnosis is mainly based on the patient's history and gynecological examination. This paper concerns a case report of cornual pregnancy, diagnosed in the 20th week of pregnancy. The diagnostic difficulties and procedures, surgical management and the patient's and newborn's outcome was described. PMID- 11208411 TI - Diagnosis and treatment of sigmoidal endometriosis--a case report. AB - Intestinal endometriosis is a rare but clinically significant complication. The most commonly involved sites are the rectosigmoid (up to 73%) and rectovaginal septum (13%). A case of a 53-year-old woman with intestinal endometriosis located in the sigmoid colon is presented with symptoms of pelvic pain and rectal bleeding. The diagnosis was established by means of colonoscopy which was performed 3 times before laparotomy. Bowel resection and pathologic study are necessary to relieve the symptoms and avoid neglecting a malignant tumor or other lesions. The postoperative course was uneventful and the patient was discharged after 13 days. PMID- 11208412 TI - Differential retinal-defocus magnitude during eye growth provides the appropriate direction signal. AB - INTRODUCTION: The rate of ocular growth can be modified by the imposition of either plus or minus lenses before the eyes, which creates changes in retinal defocus. Several hypotheses with relatively complicated mechanisms have been proposed to explain these changes, but the underlying mechanism has remained elusive. MATERIAL AND METHODS: Our new analysis using schematic models, however, provides a relatively simple and logically-consistent explanation of how retinal defocus magnitude alone during ocular growth gives the requisite sign for an appropriate change in ocular growth rate. RESULTS: During a normal genetically determined incremental increase in axial length, the presence of either an imposed plus or minus lens results in an increase or decrease, respectively, of the blur circle magnitude. Neuromodulators in the retina are proposed to regulate the sensitivity to retinal-image contrast by means of a local feedback mechanism, and the alteration in retinal-image contrast associated with the change in blur circle causes an increase or decrease, respectively, in the rate of release of neuromodulators as well as the rate of proteoglycan synthesis, the latter being associated with the structural integrity of the sclera. CONCLUSION: This provides the critical sign, as well as amplitude, information needed to modulate appropriately the rate of eye growth, to result in a decrease or increase, respectively, in the rate of ocular growth. PMID- 11208414 TI - Prenatal screening for fetal chromosomal abnormalities using ear length and shape as an ultrasound marker. AB - INTRODUCTION: To determine the range of fetal ear length and ear shape variability in healthy fetuses and in fetuses with aneuploidies in the population of patients of our institution and to evaluate the clinical value of fetal ear length and shape assessment in screening for fetal aneuploidies. MATERIAL AND METHODS: Fetal ear length was determined in 210 healthy and 15 aneuploid fetuses of pregnant women undergoing targeted ultrasound examination. Fetal ear shape was assessed in the coronal section of the head and classified into one of three categories: flat, slightly protruding, markedly protruding and curved in 175 healthy and 14 aneuploid fetuses. RESULTS: Fetal ear length showed significant positive linear relationship with gestational age, which could be described by the following equation: Ear length (mm) = 0.968566 x gestational age (weeks) - 4.81629. Fetal ear shortening below 79% of expected length yielded the sensitivity of 26.7% in the detection of fetal aneuploidy at the false positive rate of 4.8%. Finding of markedly protruding and curved ears predicted fetal aneuploidy with the sensitivity of 28.6% at the false positive rate of 1.7%. The combination of fetal ear shortening below 74% of expected length or markedly protruding and curved ears resulted in the sensitivity of 33.3% and false positive rate of 3.33% in the detection of fetal aneuploidies. CONCLUSION: Fetal ear shortening has been confirmed as a marker of fetal aneuploidies. Abnormal fetal ear shape has been shown to constitute an additional marker of fetal aneuploidies, increasing the clinical value of fetal ear length measurements. PMID- 11208413 TI - DNA microarray technology and application. AB - DNA microarrays (collections of DNA probes arranged on a shared base) have recently enlarged the spectrum of commercially available laboratory-ready kits in molecular biology. They are powerful new tools for the investigation of global changes in gene expression profiles in cells and tissues. Their assembly process is automatized and the DNA microarrays are further miniaturized. The DNA microarrays are used in search for various specific genes (e.g. connected with an infectious agent) or in gene polymorphism and expression analysis. They will be widely used to investigate expression of various genes connected with various diseases in order to find causes of these diseases and to enable their accurate treatment. Since the DNA microarray assembly technology has been based on methods widely used in the semiconductor industry, we can expect a rapid onset of the routine use of this revolutionary device. PMID- 11208415 TI - Pathogenesis of ascites in cirrhosis and portal hypertension. AB - Disturbance of the circulatory system frequently occurs in patients with cirrhosis. Cardiac index and plasma volume increase whereas mean arterial blood pressure and systemic vascular resistance decrease. Marked disturbance in vasoconstrictor and natriuretic systems also exist with activation mediators such as plasma renin, plasma noradrenaline, antidiuretic hormone and endothelin. Renal factors contribute to the pathogenesis of ascites formation although the exact mechanisms are yet to be elucidated. Several theories exist in relation to pathogenesis although none to date fully explain all of the findings observed in clinical practice. In this review, we examine the mechanisms that contribute to the development of ascites in patients with cirrhosis and portal hypertension. PMID- 11208416 TI - Mitochondrial diseases. AB - Prevalence of mitochondrial diseases equals 1:10,000 of life-born infants. Mutations of mitochondrial DNA are their most frequent cause. The study presents short description of some of these diseases. The diseases often result in encephalomyopathy, cardiomyopathy, vision disorders, dysacusis and metabolic disorders. Despite numerous studies problems associated with mitochondrial diseases have not been completely solved yet. PMID- 11208417 TI - Is TT virus (transfusion transmitted virus) a novel hepatotropic agent causing hepatitis? AB - The author presents the review of world literature regarding the infections with TT virus (Transfusion Transmitted Virus) that was discovered in Japan in 1997. PMID- 11208418 TI - Non-invasive methods of atrial function evaluation in heart diseases. AB - The article describes four essential components (hemodynamic, bioelectrical, hormonal, metabolic) of atrial function. The role atria play in heart hemodynamic performance by virtue of their reservoir, conduit and active contractile function is emphasized. Next, the authors relate various non-invasive diagnostic methods in cardiology to the estimation of particular types of atrial function in physiological and in selected pathological conditions. Only non-invasive and easy accessible in clinical practice diagnostic methods are presented. The use of echocardiography for the evaluation of hemodynamic function of atria and left atrial appendage is particularly exposed. PMID- 11208419 TI - Beta-lipoproteins influence the serum level of hepatitis C virus. AB - Low density lipoprotein receptor (LDLR) has been proposed as a candidate receptor for hepatitis C virus (HCV). According to previous reports, free beta lipoproteins in a human serum may regulate the rate of hepatocyte infection by competing with the virus. Therefore, serum HCV levels should be regulated by the rise and fall of serum beta-lipoproteins since the infection rate of virions influences HCV replication in hepatocytes and release of virions by hepatocytes. In this study, we examined the relationship between serum beta-lipoproteins and HCV-antigen (Ag) levels in patients with chronic type C hepatitis. Patients were selected based on strict criteria to eliminate other factors that might influence serum HCV levels. Serum concentrations of beta-lipoproteins and HCV-Ag were measured two or more times within 3 months for each patient. The result showed that HCV-Ag levels were negatively correlated with the increased beta lipoproteins. The results support the concept that LDLR is a HCV receptor and that beta-lipoproteins competitively inhibit the infection of hepatocytes with HCV through the LDLR. PMID- 11208420 TI - Activity of enzymes of adenyline compounds metabolism during crush and decompression of muscle tissue. Part I. Adenylate deaminase activity at experimental crush syndrome. AB - INTRODUCTION: The number of works on investigation of crush syndrome (CS) pathogenesis, of organs and enzymatic systems at traumatic toxicosis is rather limited. While the clinical current of trauma and the lethality prognosis depend on a degree of violations in them. Such investigations are necessary for opportune diagnosis and definition of a treatment tactic. To complete this deficiency, adenylate deaminase (AMPD) level was studied in twelve tissues at experimental CS in vivo. RESULTS: The experimental model of CS on white rats was caused by crush and decompression of femoral muscle tissue. The CS influence on AMPD activity was investigated in hemisphere, cerebellum, hypothalamus, pituitary body, heart, lung, liver, spleen, kidney, adrenal, crushed and not crushed muscles. In muscles, kidney, pituitary body and adrenal the activity decreased in 2 hours crush but the compensation of effect is observed after 5 hours crush. In cerebellum, hemisphere, heart, liver and lung it decreased during both of crush times. After 2 and 5 hours crush in hypothalamus and in spleen AMPD activity appeared much higher than in control. After 2 hours crush at the end of 48 hours decompression, the activity in muscles, kidney, adrenal and pituitary body was lower, in cerebellum, hypothalamus, hemisphere and heart--higher than, in lung, spleen and liver--close to control. After 5 hours crush in the majority of studied tissues at the end of decompression, the activity was below of control. The greatest deviance was observed in muscles. As to brain in cerebellum and hemisphere the parameter was close to, in pituitary body and in hypothalamus it was 1,5-fold of control. CONCLUSION: AMPD level in the most of studied tissues differs from the control at definite time of crush and decompression. These results mean the possibility of nucleotides pool balance distortion and intermediates accumulation. PMID- 11208421 TI - Activity of cathepsin D and L in the heart muscle of coronary patients during coronary--aortal bypass graft operation. AB - During coronary--aortal bypass graft operation (CABG) the period of ischaemia with cardioplegia in coronaries, is followed by the phase of reperfusion. The role of lysosomal proteases in both ischaemic and reperfusion injuries of myocardium is not very well understood. Therefore, we decided to evaluate the changes in the activity of two lysosomal proteases: cathepsin D and L taking place in the heart muscle of the coronary sufferers during CABG. Small fragments of right atrium (SFRA) were taken out during CABG: 1) just before the injection of standard St. Thomas Hospital cold cardioplegic fluid (control) 2) just after completion of artificial circulation (peak of ischaemia) and 3) after 30-40 min. of reperfusion. Cathepsins were assayed in homogenates of SFRA at pH 3.6 with haemoglobin in the absence and presence of pepstatin (cathepsin D inhibitor). Some simple calculations allow for a better insight into what is going on with lysosomal enzymes of myocardium during CABG. Essentially, total and free activity of both cathepsin D and L in the myocardium of coronary patients did not undergo significant changes during CABG. However, the values of A expressing activation (A > 1) or inactivation (A < 1) of enzymes in intralysosomal (Ai) and extralysosomal (Ae) compartment varied to a large extent (regardless of the damage of lysosomes in vivo). During ischaemia Ai for both enzymes was 2.0-2.7 while Ae for cathepsin L was about 0.7. During reperfusion Ae and Ai values ranged between 0.5 and 0.7. During CABG ischaemia period the prominent activation of both cathepsin D and L in intralysosomal compartment and inactivation, especially of cathepsin L, outside the lysosomes (outside cells) takes place probably reflecting more intensive endocytosis into cardiomyocytes. During reperfusion, the inactivation of both enzymes in both compartments takes place. Some changes seem to be irreversible, especially for cathepsin L. PMID- 11208423 TI - Is there any correlation between the total number of neutrophils in plasma and concentration of interleukin-8 in psoriatic patients? AB - INTRODUCTION: Interleukin-8 is a chemotactic agent for neutrophils which causes their simultaneous activation. This cytokine of the chemokines family contributes considerably to the processes observed in the psoriatic epidermis with the participation of neutrophils. MATERIAL AND METHODS: The level of IL-8 in plasma of psoriatic patients during the period of acute and chronic relapses, the number of neutrophils in blood, and the correlation between these parameters were analysed. The study included 55 patients affected by psoriasis (psoriasis severity and activity index ranging from 16.20 to 70.20) and 10 people of the control group. Psoriatic patients were divided into two groups: 'acute psoriasis' -with an acute relapse of the disease (up to one month)--15 patients, and 'chronic psoriasis'--with a longer period of relapse--40 patients. IL-8 plasma levels were determined with the use of the ELISA method. The total number of neutrophils was assessed in blood and smears, and calculations were performed. RESULTS: The results of the study showed higher levels of IL-8 in the plasma of patients with acute psoriasis, however, an elevated number of neutrophils in this group was not statistically significant. PMID- 11208422 TI - Effects of Bretschneider cardioplegic fluid on the lysosomal cathepsins D and L of myocardium of coronary patients during coronary-aortal bypass graft operation. AB - We evaluated the effects of replacing the standard St. Thomas Hospital (ST) cardioplegic fluid with Bretschneider (BR) fluid during coronary-aortal bypass graft operation (CABG) in patients with coronary disease. BR fluid contains enormous concentration of histidine (approximately 0.2 mole L-1): thus increased levels of histamine or other metabolites might exert some cardiovascular effects. Therefore, the changes in the level of two lysosomal proteases: cathepsin D and L of myocardium were evaluated. Small fragments of right atrium (SFRA) were taken out during CABG: just before the injection of cold cardioplegia (control), at the peak of ischaemia and after reperfusion. Cathepsin D and L were assayed in SFRA homogenates at pH 3.6 (with haemoglobin as a substrate and pepstatin as cathepsin D inhibitor). The values of parameters Ai and Ae: being the indexes of intralysosomal (Ai) and extralysosomal (Ae) activation or inactivation of cathepsins were calculated. RESULTS: With BR cardioplegia--unlikely ST fluid- there is a significant increase in total activity (T) of both cathepsins but free (F) only for cathepsin L during ischaemia with come back (to the control level) during reperfusion period. T for both cathepsins and F for cathepsin L with BR are much greater than those with ST fluid both in ischaemia and reperfusion period. BR cardioplegia results in distinct, extralysosomal activation of cathepsin L during ischaemia instead of the inhibition found with ST fluid. PMID- 11208424 TI - Sialic acids of young and old red blood cells in healthy subjects. AB - A quite simple method for obtaining young and old erythrocytes is presented. Mean corpuscular volume, glutamic oxaloacetic transaminase activity which is one of the best age parameters, and contents of total sialic acids in erythrocyte membranes were determined in whole erythrocyte population and in low (old) and high (young) density fractions separated by centrifugation of packed cells obtained from 23 healthy subjects. Glutamic oxaloacetic transaminase (GOT) activity, and contents of total sialic acids in erythrocyte membranes were significantly higher in young cells then in old ones, or in the whole population of erythrocytes. The presented results suggest that this method is simple for obtaining two different fractions of erythrocytes and that erythrocytes lose intact sialic acids together with their membrane during erythrocytes senescence. PMID- 11208425 TI - Morphological examinations of hard tissues of periodontium and evaluation of selected processes of lipid peroxidation in blood serum of rats in the course of experimental periodontitis. AB - The problem of teeth loss as a result of periodontitis is growing continuously. In the study we aimed to show the correlation between the disease and lipid metabolism disorders. We performed morphological examinations of hard tissues of rats' periodontium in the course of experimental ligature-induced periodontitis and we demonstrated the destruction of alveolodental ligament. The following changes were observed: degenerative changes including necrosis within periodontium, progressive destruction of bone mass of alveolar process of the mandible in the region of inflammatory infiltration. Simultaneously, biochemical examinations of blood serum were performed revealing decrease of basic antioxidant enzymes activities: SOD, GSH-Px, GSH-R with simultaneous increase of MDA--the final product of lipid peroxidation. PMID- 11208426 TI - Restriction fragment length polymorphisms in the apolipoprotein B gene in survivors of myocardial infarction. AB - INTRODUCTION: The aim of this study was to investigate the association between Pvu II and Msp I polymorphisms of the human apolipoprotein B gene and risk of myocardial infarction in 90 survivors of myocardial infarction. Apolipoprotein B is important in the metabolism of lipoproteins and there is an evidence suggesting that this apolipoprotein plays a central role in atherogenesis. Some polymorphisms in the apolipoprotein B gene are associated with peripheral arterial disease, coronary artery disease and risk of myocardial infarction. MATERIAL AND METHODS: DNA was prepared from the whole blood. Samples from patients and control group were digested with Pvu II restriction enzyme. Filters were prepared by Southern blotting technique and hybridized with ApoB probe (LB25 A). Genotypes for Msp I polymorphism were determined with polymerase chain reaction. RESULTS: The frequency of the rarer allele (P2) for Pvu II polymorphism in the apolipoprotein B gene was significantly higher in myocardial infarction group (P = 0.001) compared with healthy individuals. A significant association was also found between P2 allele and the age at which myocardial infarction occurred. CONCLUSION: The results suggest that in Polish population the individuals with P2 allele of the apolipoprotein B gene are at increased risk of developing myocardial infarction. No significant correlation with myocardial infarction event was found for the Msp I polymorphism. PMID- 11208427 TI - Pharmacological modification of ionic currents elicited in epithelia by sensory neuropeptides. AB - A stimulation of afferent neuronal endings in such epithelial organs as airways, colon and frog skin produces reversible hyperpolarization, usually explained as caused by neuropeptides released from sensory endings. The aim of this study was to examine pharmacological modifications of these electrophysiological reactions, which were evoked by the inhibition of Na+ or Cl- transepithelial transport by application of amiloride (AMI) and bumetanide (BUME). The tissues were mounted in a modified Ussing chamber which was additionally equipped with a nozzle connected to a peristaltic pump and acting as a stimulation device. In the resting, control conditions the transepithelial potential differences--PD of tracheal and colonic walls and frog skin were: -3.3 +/- 0.4, -3.0 +/- 0.4 and -16.5 +/- 4.1 mV, respectively and hyperpolarization after mechanical stimulation--dDP for the same organs was: -1.2 +/- 0.3, -1.2 +/- 0.3 and -2.4 +/- 0.4, respectively. Preincubation with AMI influenced the dPD in all tissues but the PD of the frog skin was only depolarized. Preincubation of the tissues with BUME diminished dPD in all organs. A hypothesis was put forward that epithelial hyperpolarization of tracheal and colonic walls depends on the combined augmentation of Na+ and Cl- transport processes, whereas epithelial hyperpolarization of frog skin depends entirely on Na+ currents and all these transepithelial ionic currents have an adapting value. PMID- 11208428 TI - Dendritic and cancer cells in the breast tumors--an immunohistochemical study: short communication. AB - Normal and dysplastic mammary glands express immunocompetent S-100 protein positive dendritic cells (DCs), which are located in a regular pattern, in the suprabasal cell layer of the ducts and alveolar nodules. The epithelial cells, however, are S-100 protein negative. Since some breast cancers also express the S 100 protein, our aim was to check the diagnostic and prognostic value of the S 100 protein distribution combined with the tumor grade and expression of synaptophysin (Syn), chromogranin A (Chg A), c-erbB-2 oncoprotein and p53 protein in infiltrating and metastatic breast tumors. Applying immunohistochemical methods, we show in paraffin- or frozen breast tissue sections that in some cases of the infiltrating breast carcinomas, S-100 protein positive cells do not appear, whereas in other cases, either S-100 protein positive DCs are closely associated with cancer cells, or the cancer cells themselves stain positive to S 100 protein. However, we found no correlation between the S-100 protein expression and other investigated parameters. PMID- 11208429 TI - Effect of propranolol and midazolam therapy on hemodynamic parameters in rabbits. AB - Some of anesthetic drugs cause cardiac arrhythmia, myocardial depression, blood pressure as well as hepatic and renal blood flow decrease. The aim of the following research study was the evaluation of midazolam effect on hemodynamic parameters in propranolol-treated rabbits. The following parameters: cardiac output and stroke volume, peripheral blood resistance, heart rate and blood pressure were estimated in the hemodynamics study. Blood pressure was significantly higher in case of propranolol and midazolam therapy as compared with midazolam alone. Blood pressure inconstancy did not exceed 20% of the initial value. Midazolam did not improve the depressive effect of propranolol on heart rate. The peripheral vascular resistance in coherent propranolol and midazolam therapy oscillated at the values observed after sole midazolam administration. After midazolam administration with propranolol, insignificant increase of cardiac output and stroke volume during the first minutes of experimental protocol correlated with marked decrease of peripheral blood resistance at the same time. PMID- 11208430 TI - Lipid peroxides, anti-oxidants and nitric oxide in patients with pre-eclampsia and essential hypertension. AB - INTRODUCTION: The aim was to study the role of lipid peroxides, nitric oxide and anti-oxidants in pre-eclampsia and essential hypertension. MATERIAL AND METHODS: The study was done in 28 patients with pre-eclampsia and 30 patients of essential hypertension. The plasma concentrations of lipid peroxides as a measure of pro oxidant status, nitric oxide and RBC content of anti-oxidants were measured in these patients and compared with controls. RESULTS: It was observed that in patients with pre-eclampsia the plasma concentrations of nitric oxide and lipid peroxides were elevated with a decrease in those of anti-oxidants such as catalase and superoxide dismutase and a concomitant increase in that of glutathione peroxidase. On the other hand, in patients with essential hypertension, the concentrations of nitric oxide and superoxide dismutase were found to be low where as that of lipid peroxides were high. When the lipid peroxides/nitric oxide (LP/NO) ratio was calculated a far more significant rise in the concentrations of lipid peroxides compared to NO levels was noted especially in patients with pre-eclampsia and patients with uncontrolled essential hypertension. CONCLUSIONS: These results suggest that oxidants and anti oxidants are altered in human essential hypertension and pre-eclampsia and that they may play a significant role in their pathophysiology. PMID- 11208431 TI - Permissive role of neutrophils in pathogenesis of indomethacin-induced gastric lesions in rats. AB - INTRODUCTION: We examined the possible role of neutrophils in the pathogenesis of indomethacin-induced gastric lesions, in comparison with prostaglandin (PG) deficiency. MATERIAL AND METHODS: Rats were given indomethacin (35 mg/kg, s.c.) and killed 4 hr later. Gastric motility, mucosal PGE2 levels, and myeloperoxidase (MPO) activity were measured following indomethacin. Atropine was given s.c. 30 min before administration of indomethacin, while 16, 16-dimethyl PGE2 (dmPGE2) or anti-rat neutrophil antiserum (ANS) was given i.v. 10 min or 1 hr, respectively, before indomethacin treatment. RESULTS: Indomethacin reduced PGE2 contents in the stomach and produced hemorrhagic lesions in the stomach, with an increase of gastric motility and MPO activity. Indomethacin-induced gastric lesions were significantly prevented by dmPGE2 as well as atropine, at any time points during a 4 hr-test period. By contrast, the pretreatment of ANS did not prevent the development of gastric lesions when examined at either 1, 2 or 3 hr following indomethacin, but significantly reduced the severity of these lesions at 4 hr after indomethacin treatment. Both dmPGE2 and atropine inhibited the increase of gastric motility and MPO activity in response to indomethacin, whereas ANS prevented the increase of MPO activity, without any effect on the gastric hypermotility. CONCLUSION: These results confirmed that indomethacin-induced gastric lesions occurred in association with gastric hypermotility, in both atropine and PG-sensitive manners, and further suggest that the neutrophil activation/migration is not sufficient by itself to induce damage in the stomach and may be implicated in the process of later extension of damage. PMID- 11208432 TI - Causes and pathomechanisms of oesophageal varices development. AB - Portal hypertension is a common clinical syndrome with chronic liver diseases and is characterised by a pathological increase in portal pressure. Moreover, portal hypertension is associated with increased portal blood flow. Increased vascular resistance in portal hypertension is because of an increase in both intrahepatic and portosystemic collateral resistance. Chronic elevations in systemic and splanchnic blood flow have been documented as key elements of hyperdynamic circulatory state of hypertensive animals and humans. Peripheral vasodilatation initiates the development of the classic profile of decreased systemic elevated splanchnic blood flow and elevated cardia index that characterises this state. Portosystemic collaterals develop as a result of portal hypertension. This is the central pathophysiological event that leads to bleeding from oesophagogastric varices and portosystemic encephalopathy. Collateral vessels respond to various vasoconstrictors and vasodilators.--Varices in the distal 5 cm of the distal oesophagus are easily identified by endoscopy because of their superficial location in the lamina propria and therefore are must apt to bleed and why the current practise of endoscopic therapy is likely to be successful in obliterating the varices. In patients with oesophageal varices the dilated deep intrinsic veins displace the superficial venous plexus, assume a supepitheal position and are endoscopically visible as teleangiectasia, cherry red spots, red colour signs, hemocystic spots, red wale markings or varices on varices. As alternative endoscopic way of treatment the paravariceal injection has been propagated by our group thus preserving the pathophysiologic collaterals and preventing early new formation of collaterals and rebleeding. Pathophysiologically the concept of erosion has been abandoned and replaced by the explosion theory: bleeding probably occurs when the expanding force by pressure and flow can no longer be counter-balanced by the variceal wall tension; at this point the varices rupture and bleed. When the varix distension has increased, the radius has increased and the wall thickness decreased. Thus early diagnosis of patients with a high tendency to bleed can easily be made by endoscopy, measuring portal and/or oesophageal-variceal pressure and characteristising the chronic liver disease according to the Child-Pugh-classification. PMID- 11208433 TI - Prevalence, course and risk factors of diabetic nephropathy in type-2 diabetes mellitus. AB - Contrary to the well-known features of diabetic nephropathy (DNP) in type-1 diabetic patients (pts), the prevalence, course and risk factors of DNP in in type-2 diabetic pts are not clear. The aim of the present study was to assess the prevalence of microalbuminuria (MA) and macroalbuminuria (MAA), their relationship with other diabetic complications and with some known cardiovascular risk factors in 200 in type-2 diabetic pts (100 females and 100 males). 68 pts (33%) were normalbuminuric (NA), 55 (27.5%) had MA and 77 (38.5%) had MAA. There was no significant difference among these three groups in age, BMI or the time actually elapsed since the diabetes and hypertension were diagnosed. BMI was high in each group (28.8 +/- 5.29, 28.0 +/- 5.2 and 29.8 +/- 4.6 kg/m2 mean +/- SD). 65% of pts with NA, 77% of those with MA and 81% of pts with MAA had hypertension. MAA pts were more frequently smokers and former smokers, than MA and NA pts (56% vs 32% and 22%). Average GRF values (ml/min/1.73 m2) were 71.9 +/ 26.8 in NA pts, 82.3 +/- 36.8 in MA pts and 56.3 +/- 32 in MAA pts. There was no significant correlation between the urinary albumin excretion (UAE) and glycemic control, serum (se) cholesterol and se HDL cholesterol. At the same time UAE showed a significant positive correlation with se trigliceride (P < 0.01), se uric acid (P < 0.01) and se creatinine (P < 0.01) while a significant negative correlation was found with GFR (P < 0.01). Diabetic non-proliferative retinopathy (RP) was detected even in NA pts (27%) while 51% of MAA pts were without RP. 56% of NA pts, 57% of MA pts and 93% of MAA pts had macroangiopathy. CONCLUSIONS: (1) renal function can be impaired even in type-2 diabetic pts with NA and MA, (2) well-known cardiovascular risk factors seem to have a close relation with renal damage in type-2 diabetes (3) renal lesions in type-2 diabetic pts may be caused by diseases other than diabetes (e.g. arteriosclerosis, hypertension) (4) unlike in type-1 diabetes, where the strict glycemic control is the main preventive factor of DNP, in type-2 diabetes, the control of hypertension, hyperlipidemia, obesity, hyperuricemia may have priority. PMID- 11208434 TI - Lung resection in a neoadjuvant protocol. AB - Neoadjuvant therapy was defined as a cytoreductive therapy administered prior to a definitive locoregional treatment--surgical resection. While surgical resection can be curative in patients diagnosed with localized early-stage non-small cell lung cancer, patients with nodal (N1, N2) disease are generally not candidates for exclusive surgery. Inductive therapy can improve the microscopic metastatic disease, eradicate the primary tumor and thereby improve survival. PMID- 11208435 TI - Modification of corporal weight, body fat distribution, blood lipids and glucose levels in oral contraceptive users. AB - The association between oral contraceptives and the modification of corporal weight and body fat distribution is controversial. The characteristics of the menstrual cycle, lipids and glucose levels were also analyzed. Thirty women who received ethinylestradiol 0.035 mg and norethindrone 0.400 mg for one year were studied. The following variables were analyzed every 3 months: weight, body mass index (BMI), hip perimeter, waist perimeter, waist-hip ratio (WHR), duration of menstrual cycle, quantity of uterine bleeding, as well as blood levels of cholesterol, triglycerides and glucose. Waist and hip perimeters increased during the third evaluation; as well as the BMI starting from the second evaluation. The triglycerides levels rose from the first evaluation. No modifications were found in the WHR, glucose and cholesterol levels and the duration of the menstrual cycle, but the quantity of uterine bleeding decreased from the third month. The oral contraceptive significantly increased BMI and triglycerides level, but no changes were detected in body fat distribution, cholesterol and glucose levels. Uterine bleeding decreased from the first evaluation. PMID- 11208436 TI - Twins in Jos Nigeria: a seven-year retrospective study. AB - INTRODUCTION: A retrospective analysis of twin pregnancy was carried out between 1st January 1992 and 31st December 1998 to determine the incidence, epidemiological variables perinatal and maternal outcome of twin pregnancy in the institution. MATERIAL AND METHODS: The case notes of the 413 twin pregnancy, 6 triplets and 1 quadruplet delivered during the period, and the labour records of all the deliveries were analyzed. Statistical analysis was with chi-squared test. The level of significance was set at 5%. RESULTS: The incidence of twin pregnancy was 28/1000, triplet 0.4/1000 and quadruplet 0.07/1000. The age range of the twin mothers was 15-47 years with a mean of 28 +/- 5.4 years. The parity range was 0 14 years with a mean of 3.3 +/- 2.6. Rising maternal age and parity were associated with twinning rate. The mean fetal weight was 2.21 +/- 0.66 kg. There was no statistical significant difference in weight between the 1st and 2nd twins. Male babies however weighed heavier (p < 0.02) than the female infants. The incidence of low birth weight babies (< 2500 g) was 58.7% with a perinatal mortality rate of 278.4/1000. The perinatal outcome was worst for the very low birth weight babies (< 1500), 817.5/1000 8.5% of twin mothers had a retained 2nd twin. The perinatal outcome of the 27 unbooked mothers who delivered their 1st twin at home was (12) 44.4/1000, compared to the rate of 12.5/1000 (1) in 8 booked mothers, who delivered the 1st twin in the hospital. Among the 771 babies who were alive at the time of presentation in the labour ward, delivery by caesarean section had a better perinatal outcome (6.8%), compared to spontaneous vaginal delivery (13.1%) and assisted breech delivery (21.4%). The unbooked twin mothers had a perinatal mortality rate of 318.7/1000 compared to booked mothers 82.3/1000. The overall perinatal mortality rate was 186.4/1000. The clinical causes of death were prematurity 74.6%, retained 2nd twin 7.3%, antepartum haemorrhage 6.1%, severe pregnancy induced hypertension/eclampsia 3.0%, birth asphyxia 2.4%, congenital malformation 1.8%. The incidence of postpartum haemorrhage was 3% and there was no maternal mortality in the series. The institution will need to put in place adequate resuscitating facilities and manpower to manage the low birth weight infants so as to reduce the current high perinatal wastage. PMID- 11208437 TI - Outcomes of conservative treatment of primary vesicoureteral reflux in children. AB - INTRODUCTION: The purpose of the study was to evaluate the efficacy of conservative treatment of primary vesicoureteral reflux. MATERIAL AND METHODS: Material included 179 children aged 1-15. Methods included voiding cystography in all the patients. Normal result of the examination was assumed as the regression of reflux. RESULTS: Conservative treatment resulted in the regression of 58% of I degree-IV degree refluxes. CONCLUSIONS: The most significant factors determining the efficacy of conservative treatment of primary vesicoureteral reflux are: reflux grade and child's age at diagnosis. PMID- 11208438 TI - HLA class I antigens in families with coeliac disease. AB - The aim of the study was the analysis of the frequency of HLA class I antigens in the Polish population of children suffering from coeliac disease and their families, as well as the estimation of the relative risk of incidence, etiologic fraction (EF) and preventive fraction (PF) indexes. Forty-six probands' families were included in the typing: 69 children with coeliac disease confirmed clinically and histologically, 49 healthy siblings and 91 parents. The HLA antigens were typed with routine Terasaki an McClelland's two-stage microcytotoxic assay in NIH modification. The following antigens occurred significantly more frequently (p < 0.0000...1) in phenotypes of children with coeliac disease: HLA-A1 (chi 2 = 35.90; RR = 4.3; EF = 0.44), -B8 (chi 2 = 88.20; RR = 8.8; EF = 0.58) and Cw7 (chi 2 = 55.24; RR = 7.5; EF = 0.69). The positive correlation for the specificity of HLA-A1, -B8 was proved also in siblings (chi 2 = 16.03; chi 2 = 18.10) and parents (chi 2 = 15.67; chi 2 = 32.67). The presence of antigens HLA-A1, -B8 in the phenotype may be the risk factor predisposing for the manifestation of hypersensitivity to gluten. PMID- 11208439 TI - Studies of the effectiveness of interferon alpha treatment for chronic hepatitis C in children. AB - INTRODUCTION: The significance of hepatitis C infection in Poland, particularly in a pathology of the developmental age still increased. The aim of the study was the analysis of interferon alpha therapy efficacy in children with chronic C hepatitis. MATERIAL AND METHODS: 30 children (aged from 3 years to 15 years, 16 females, 14 males) were included in the study. In each patient HCV infection was confirmed by the serological, molecular (with identification of HCV genotype) and histopathological methods. The duration of observation of HCV-infected children after the diagnosis was made followed for at least 6 months. Transaminase level in each case was 50% higher than normal. The schema of interferon alpha treatment was: 3 MU 3 times a week subcutaneously for 25 weeks. Time of observation started at the beginning of the therapy and finished 1 year after the end of the treatment. RESULTS: The analysis of the HCV genotypes showed the predominance of the genotype 1 (66.7%): subtype 1a was found in 20% patients, subtype 1b--in 43.5% children. Genotype 4 (subtype 4c4d or 4b) was confirmed in 30% patients, genotype 3 (subtype 3a) in 3.3% patients. In the histopathological picture of the liver predominated minimal or moderate inflammation activity (grading: 1--in 50%, 2--in 46.6%, 3--in 3.4%) and little fibrosis (staging: 0--in 80%, 1--in 13.3%, 2- in 6.7%). In many children mild side effects of interferon alpha therapy were observed: pseudoinfluenzal symptoms (in 46.7%), lack of appetite (in 16.7%), abdominal pain (in 10%), thrombocytopenia (in 6.7%), granulocytopenia, hair loss, irritability, itching of the skin (in 3.4%). At the end of therapy in 36.7% patients serum HCV-RNA was undetectable. The percentage of children without serum HCV-RNA decreased 6 months after the end of therapy to 20% patients and a year after the end of therapy to only 13.6% children. In children with HCV-RNA elimination was observed early reduction of ALT level. For the definition of the predictive factors of good prognosis patients were divided into 2 groups: group I (without HCV-RNA elimination at the end of the treatment) and group II (patients HCV-RNA negative a year after the end of therapy). Both group of children were similar in respect of age, disease duration and interferon alpha dosis/m2. At the beginning of the treatment mean ALT level was statistically higher in group II than in group I. IL-2 level was significant higher in group II than at the beginning, after 2 and 4 months of the therapy. There were no significant differences in IL-1 beta, IL-4 and IL-6 level between patients in group I and II. The differences in ALT activity during IFN-therapy between 2 groups of patients were statistically significant; since second month of therapy higher ALT level was observed in a group of patients without HCV-RNA elimination. In the histopathological picture of the liver a year of the end of therapy in 20% children reduction of inflammatory activity and progression of fibrosis in both group of patients was observed. CONCLUSIONS: Because of a little efficacy, high costs, psychological load of young patients and possible following consequences of the interferon alpha therapy it is necessary to manage the further researches to find a new method of treatment of chronic C hepatitis. High ALT activity and elevated IL-2 level before treatment seems to be predictive factors of the good response to interferon alpha therapy. PMID- 11208440 TI - HBV-DNA level in blood serum as a predictor of good response to therapy with interferon-alpha-2b of patients with chronic hepatitis B. AB - The prevalence of hepatitis B infection in population in Poland is low and averages 1-1.5%. However, it means that about 380,000 Poles constantly or temporarily replicate HBV. Chronic HBV infection is associated with increased risk of serious liver diseases and it is estimated that 25-40% of patients with chronic hepatitis B will die prematurely of cirrhosis or primary liver cancer. Up to the present, interferon-alpha (IFN-alpha), with low response rate between 25 55% and some limitations of therapy, has been the only available treatment for chronic hepatitis B. A favorable outcome of IFN-alpha therapy is associated with some prognostic factors, not accepted by all investigators, such as low level of HBV-DNA in serum. The aim of this study was to assess the efficacy of therapy with IFN-alpha 2b (Intron A), administered s.c. 5 MU x 3/week for 16 weeks, in 65 patients with chronic hepatitis B, divided into groups according to the baseline HBV-DNA level. Except for serum HBV-DNA level, there were no demographical and biochemical differences between all the treated groups. The patients were followed-up for 12 months. Sustained response (SR) to the therapy (defined as ALAT normalization, loss of detectable HBV-DNA, seroconversion HBeAg to anti HBeAg and improvement in liver histology) was observed in 16 (57.14%) of patients in the group with HBVDNA level < 1000 pg/ml, in 6 (37.5%) with HBV-DNA level of 1001-3000 pg/ml, in 4 (28.57%) with HBV-DNA level of 3001-5000 pg/ml and only in 2 (28.57%) of patients in group with HBVDNA level > 5000 pg/ml. We conclude that IFN-alpha is particularly useful in therapy of patients with chronic hepatitis B with low levels of HBV-DNA. The baseline HBVDNA level < 1000 pg/ml in serum is the predictor of good response to IFN-alpha therapy. PMID- 11208441 TI - Reactivity of cerebral arteries after subarachnoid hemorrhage in rats after phosphoramidon administered. AB - The aim of the study was to quantify cerebral vasospasm in rats after subarachnoid hemorrhage (SAH) by morphometric examination of basilar artery and to evaluate the influence of Phosphoramidon on basilar artery constriction. The rat cisterna magna (CM) was cannulated and after 7 days SAH was developed by administration of 100 microliters autologic, non-heparinized blood to the CM. The sham subarachnoid hemorrhage was developed by intracisternal administration of 100 microliters of artificial cerebrospinal fluid. After 60 min and after 24 h Phosphoramidon was injected into the CM in a dose of 40 nmol diluted in 50 microliters of cerebrospinal fluid. After perfusion, the brain was removed from the skull and histological preparations of the basilar artery were made. The internal diameter and wall thickness of basilar arteries were measured by interactive morphometric method. The most severe vasospasm was found in rats after SAH and the administration of Phosphoramidon in the late phase after SAH caused the dilatation of the basilar artery. The presence of numerous infiltrations composed of neutrophils and macrophages correlated with advanced vasospasm (index of constriction 5 times lower than normal), suggesting the role of other factors participating in the late phase of vasospasms after SAH. PMID- 11208442 TI - Moderate systemic hypothermia and cold crystalloid cardioplegia influence on myocardial ischemic and revascularisative injury. AB - The number of granulocytes, their ability to generate superoxide anion (O2-) and the activities of Cu, Zn--superoxide dismutase (SOD-1), glutathione peroxidase (GSH-Px), catalase (CAT) as well as malonyldialdehyde (MDA) concentrations in erythrocytes in the blood extracted from the venous sinus and aorta under coronary artery bypass were examined with the use of St. Thomas Hospital cardioplegic solution. Specimens at the peak of ischemia of the right atrium for ultrastructural examination of the endothelial cells of capillary vessels and sarcomers were taken. The blood was obtained during cardiopulmonary bypass (CPB) before the aorta clamping and immediately after aorta declamping (peak of ischaemia) between 1-3 minute and 10-13 minute of reperfusion. Increase of the number of granulocytes both in the coronary sinus and aortal blood at all examined intervals as well as decrease in the number of ones in sinus compared with aortal blood was noted. The ability to produce superoxide anion radical decreased at the peak of ischemia and during reperfusion. The activity of SOD-1 was lower both after the period of ischemia and reperfusion. The increase in aortal blood activity during reperfusion was characteristic of GSH-Px; the activity was higher in the blood sample from the coronary sinus taken during ischemia and initial reperfusion. With the exception of the initial reperfusion the activity of CAT diminished in all observed cases. MDA concentration did not demonstrate any significant changes with the exception of the initial reperfusion in the aortal blood and later towards the end of reperfusion in the blood from the coronary sinus. Ultrastructural studies indicated overhydration of the cells both in the endothelium and the intercellular space. The obtained data demonstrate that the applied cardioplegic solution protects the myocardium from harmful effects of reactive oxygen species produced as a result of ischemia and reperfusion. PMID- 11208443 TI - Changing epidemiology of hepatitis A virus infection--a comparative study in central eastern Poland (1990-1999). AB - A comparative seroepidemiological study (1990 vs. 1998/99) on HAV infection, was carried out in population from middle-eastern Poland. Anti-HAV was tested in 1450 subjects from 0 to over 50 years of age and the results were compared with those observed in 1990, in 1000 individuals of the same age range and from the same geographical area. Overall anti-HAV prevalence was 58.4% in 1990 vs. 30.6% in 1998/99. This decline of HAV infection in Polish population indicates that the number of non-immune adults is increasing, with higher risk of symptomatic infection in the near future. The surveillance and prevalence data presented here have implications for developing the strategy for use of hepatitis A vaccine. PMID- 11208444 TI - Utility of the triple test in the detection of abnormalities of the feto placental unit. AB - INTRODUCTION: The objective of the study was to examine the relationship between the concentrations of maternal serum AFP, total beta-hCG and uE3 and the presence of various pathologies of the feto-placental unit. MATERIAL AND METHODS: The triple test was performed in the group of 882 pregnant women between the 14th and 21st week of gestation. The control group consisted of 863 pregnant women with unburdened obstetric anamnesis with an uneventful singleton pregnancy. The examined group consisted of 19 pregnant women with fetal aneuploidies and other pathologies of the feto-placental unit (oligohydramnios, vacuolization of the trophoblast). In the maternal sera concentrations of AFP, total beta-hCG and unconjugated estriol were determined. The risk of fetal trisomy 21 was calculated using DOWNS and PRISCA 3.0 software (cut-off 1: 295), Ulm Index was also calculated (cut-off 8.1). RESULTS: In the group of pregnant women with fetal chromosomal aneuploidies no significant changes of the examined parameters were established. In the cases of oligohydramnios AFP concentrations significantly increased, in the cases of fetal triploidy the concentrations of all examined parameters decreased. In the cases of vacuolization of the trophoblast concentration of the total beta-hCG increased. CONCLUSION: Oligohydramnios, fetal triploidy and vacuolization of the trophoblast caused significant changes of the concentrations AFP, total beta-hCG and unconjugated estriol in maternal sera. PMID- 11208445 TI - A case of Klinefelter's syndrome associated with unilateral renal aplasia. AB - We describe a 22-year-old patient with Klinefelter's syndrome associated with unilateral renal aplasia. Unilateral absence of kidney was detected in our ongoing screening for renal abnormalities by renal ultrasound in male hypogonadism. The present abnormality may be a co-existing entity or previously unrecognized abnormality associated with Klinefelter's syndrome since there is not reported systematic screening for urinary tract abnormalities in patients with Klinefelter's syndrome in the literature. PMID- 11208446 TI - Neurogenic pulmonary oedema in a 13-year-old boy in the course of symptomatic epilepsy--case report. AB - Pulmonary oedema with severe, dramatic course following CNS injury was termed neurogenic pulmonary oedema (NPO). NPO was mainly described as a consequence of grand mal seizures, subarachnoid bleeding, intracranial bleeding or head injury. However, the pathogenesis of NPO is not entirely clear yet. In the majority of cases, early or classic symptoms of pulmonary oedema are evident from several minutes up to several hours after CNS damage. Dyspnoea, chest pain, bloody expectoration are observed shortly after consciousness disorders, although NPO may occasionally be diagnosed on the basis of chest x-ray in patients with no clinical symptoms. Tachypnoea, tachycardia, rales without any changes in cardiac system are usually observed during physical examination. The ailments withdraw quickly in the majority of patients, who may require oxygen therapy at most. NPO has been well-known in adults, but our knowledge of its occurrence in children is still rather sparse. The current work presents a case of a 13-year-old boy with pulmonary oedema as a post-seizure complication. PMID- 11208447 TI - Subdural empyemas--a rare complication of meningococcal cerebrospinal meningitis in children. AB - Subdural empyemas are a rare, life-threatening complication of cerebrospinal meningitis. Two cases of subdural empyemas which occurred as early complications after cerebrospinal meningitis in infants are presented. Utilization of modern diagnostic methods, such as US and CT allowed to establish an early diagnosis, which made it possible to institute appropriate treatment, involving evacuation of the purulent content with local application of antibiotics followed by intravenous antibiotics well penetrating the fluid-filled compartments of the CNS. Early institution of treatment gave a chance of complete recovery in both presented cases. PMID- 11208448 TI - Echocardiographic assessment of right atrial thrombus related to the implanted port device in patient receiving chemotherapy for non-Hodgkin's lymphoma. AB - The case of a potentially life-threatening complication related to the use of implanted port device in a 8 year old Non-Hodgkin's Lymphoma patient receiving chemotherapy is described. The device was inserted in early 1997 and used repeatedly for chemotherapy without any complications. In late 1997 during routine screening for cardiac left ventricular function before re-introduction of chemotherapy, an abnormal 1.43 x 1.53 cm mass, consistent with a non-mobile thrombus was found in the right atrium. The initial thrombolytic therapy with recombinant tissue plasmin activator (rt-PA) infused by a central venous catheter was combined with daily echocardiographic examination in order to assess both the timing and mode of thrombus resolution. After 8 days systemic fibrinolytic therapy was discontinued as major hemorrhage from venipuncture sites occurred and the clot dissolution was not obtained. Patient underwent right atriotomy utilizing cardiopulmonary bypass and subsequent surgical thrombus removal was successful. The study evaluated the contribution of two-dimensional echocardiography (2D) in the follow-up of vascuport and other central venous catheter (CVC) location and early diagnosis of related complications such as thrombi. The authors consider that pulmonary flow analyzed with Doppler echocardiography as a reliable, suitable and non-invasive method to evaluate increased pulmonary artery pressure in children with right atrial thrombi and probability of pulmonary microembolism or embolism. As the incidence of right atrial thrombi is highly associated with the catheter tip position in the right atrium, in contrast to their positioning in the superior vena cava or in its junction with the right atrium, the authors recommend that special attention and effort should be given to placing of the catheter tip in the superior vena cava or in its junction with the right atrium avoiding the right atrium during the implantation procedure. The surgical right atrium thrombus removal in patients with no clot dissolution despite systemic thrombolytic treatment underscores the importance of surgical therapy in treating this life-threatening complication of indwelling catheters. PMID- 11208449 TI - Effectiveness of high resolution ECG spectral analysis in discrimination of patients prone to ventricular tachycardia and fibrillation. AB - INTRODUCTION: To improve the diagnostic power of high resolution electrocardiography for discriminating patients at risk of ventricular arrhythmias, new methods based on spectral analysis have been used in recent years. The purpose of this study was to evaluate the effectiveness of these methods for predicting the risk of ventricular tachycardia and ventricular fibrillation in patients after myocardial infarction. MATERIAL AND METHODS: High resolution ECG were recorded in 129 post-infarction patients and 23 healthy volunteers. Of the post-infarction patients: 62 presented with ventricular tachycardia, 23 with ventricular fibrillation, while 44 had no clinically relevant arrhythmias. The ECG signals were recorded in three orthogonal X, Y, Z leads and averaged using cross-correlation method. Spectral analysis was performed by fast Fourier transform and the parametric modeling method with autoregressive model. Spectral analysis data were evaluated quantitatively by computing normality factor for FFT and spectral factor for AR. RESULTS: Both methods were found to be useful for evaluating the risk of arrhythmias. The sensitivity of ventricular tachycardia risk evaluation was higher (81%--FFT, 73%- AR) than that of evaluating the risk of ventricular fibrillation (30%--FFT, 48%- AR). The specificity in post-infarction patients without arrhythmias (93%--FFT, 84%--AR) was as high as that in healthy subjects (96%--FFT, 87%--AR). CONCLUSIONS: Spectral analysis of HRECG is an effective method for evaluating the risk of VT and VF in patients after myocardial infarction. PMID- 11208450 TI - Hyperacute infarction: early CT findings. AB - The aim of our study is to determine how early and reliably ischemic brain infarcts can be detected on CT scanning. We report two cases of an early CT finding of acute ischemic infarcts where CT examination was obtained within the first 3 hours of onset of neurological symptoms. CT examination showed blurred outlines and decreased attenuation of the left lentiform nucleus, loss of the white-gray matter interface in the left insular cortex and left cortical global hypoattenuation with obliteration of left cortical sulci in one patient. In second patient CT showed the following: hyperdense left middle cerebral artery, loss of clear margins of left lentiform nucleus, subtle focal cortical hypodensity in the left fronto-parietal area with signs of mass effect in the form of ventricular compression. CT is still the first choice in the deferential diagnosis of acute stroke. Although older literature positions have suggested that CT was negative during the first 48 hours, modern CT technology can demonstrate positive findings even in the first 3 hours of onset. This is important in patients with acute stroke, as thrombolytic therapy when elected, has to be given within the first 3-6 hours after onset of symptoms. To determine how early and reliably ischemic brain infarcts can be detected on CT scanning, we report two cases of an early CT finding of acute ischemic infarcts where CT examination was obtained within the first 3 hours of onset of neurological symptoms. PMID- 11208451 TI - Alcohol and the developing fetus--a review. AB - Fetal alcohol syndrome (FAS) is a collection of signs and symptoms seen in some children exposed to alcohol in the prenatal period. It is characterized mainly by physical and mental retardation, craniofacial anomalies and minor joint abnormalities. However, with the increasing incidence of FAS, there is a great variation in the clinical features of FAS. This article describes in detail these clinical features. Due to ethical reasons it is not possible to perform experiments on pregnant women. Hence to study the effects of alcohol, various animal and avian experimental models have been chosen. The various experimental findings and human correlation are described. The exact mechanism by which alcohol induces its teratogenic effects is not known. The possible mechanisms are discussed. Measures to prevent the occurrence of FAS have been suggested. PMID- 11208452 TI - Role of cytokines in pathogenesis of endometriosis. AB - Sampson's theory stating that endometrial cells and fragments desquamate during the menstrual period are transported through Fallopian tubes into the peritoneal cavity where they implant, proliferate and develop into endometriotic lesions is generally accepted [1]. Accumulating data suggest that deficient immunity against retrograde endometrium during menstruation may be involved in the pathophysiology of endometriosis. Recent studies in women with endometriosis have demonstrated functional changes in several immunologic components in the peritoneal fluid as well as in sera of those patients. It was shown, for instance, that a wide pattern of cytokines are involved during endometrial cells implantation, proliferation and forming of endometriotic lesions. Those factors play a critical role in decreased immunologic surveillance, recognition and destruction of ectopic endometrial cells and possible facilitation of the implantation of ectopic endometrial tissues. The present review summarises the current knowledge on the role of different cytokines in the pathophysiology of endometriosis. PMID- 11208453 TI - Vascular endothelial growth factor (VEGF) and its effect on angiogenesis. AB - The article discusses the role of vascular endothelial growth factor(VEGF) in angiogenesis in embryonic development, particularly the effect of VEGF on capillary formation in response to chronic tissue ischemia and hypoxia. The sources and action of numerous angiogenic and angiostatic factors responsible for morphologic development of endothelial cells and disturbances in VEGF and FGF secretion are also presented. Increased VEGF and VEGF receptor expression enhances vascular permeability and angiogenesis, and is the cause of tissue edema as well as tumor and metastasis formation. VEGF appears to have a beneficial effect only in ischemic diseases of the heart and peripheral vessels. The article highlights the therapeutic implication of VEGF suppression in other areas of ischemia. PMID- 11208454 TI - Newer uses of glucose-insulin-potassium regimen. AB - Diabetic ketoacidosis and moderate degree of hyperglycemia can be managed by glucose-insulin-potassium (GIK) regimen. The GIK regimen is also useful in the treatment of acute myocardial infarction (AMI). But, the exact mechanism(s) of the beneficial action of GIK regimen is not known. I suggest that glucose-insulin can suppress the secretion and antagonize the harmful effects of tumor necrosis factor alpha (TNF alpha) and macrophage migration inhibitory factor (MIF). If this is true, it suggests that GIK regimen may be useful in septicemia and septic shock, and other inflammatory conditions such as ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus and cancer, conditions in which TNF alpha and MIF appear to play a major role. PMID- 11208455 TI - A C2077T polymorphism of the type B human natriuretic peptide receptor gene is not associated with myocardial infarction. AB - INTRODUCTION: We examined previously the genomic structure of the human natriuretic peptide receptor type B (hNPRB) gene and reported a C2077T polymorphism located in exon 11 of the gene. We now have studied the C2077T polymorphism in myocardial infarction [MI] patients and non-MI [control] subjects to evaluate the value of this polymorphism as a marker for MI. MATERIAL AND METHODS: 302 subjects (163 MI patients and 139 non-MI age-matched control subjects) were studied. PCR-restriction fragment length polymorphism analysis (PCR-RFLP) was developed to detect the C2077T transition. RESULTS: The distribution of C2077T polymorphism genotypes in the MI patients (CC:CT:TT, 47.2%:41.1%:11.7%) was not significantly different from that in the control patients (CC:CT:TT, 53.2%:40.3%:6.5%) (chi 2 = 2.73, p = NS). Allele frequencies of the C2077T polymorphism were f(C/T) 68.2%/31.8% in the MI group and 73.4%/26.6% in the control group. However, no association was found between this polymorphism and clinical diagnosis of MI. CONCLUSION: Our data indicate that the C2077T polymorphism is not a useful marker of the relation between the hNPRB gene and MI in the Japanese and variations of the hNPRB gene that may be in linkage disequilibrium with this polymorphism do not play a causative role in MI. PMID- 11208456 TI - Decreases of brain serotonin following a food restriction schedule of 4 weeks in male and female rats. AB - Male and female rats fed on a restricted feeding (RF) schedule of 4 weeks to produce 20-25% reduction in body weight, were killed before (starved) and after (fed) the presentation of food to compare 5-hydroxytryptamine (5-HT) metabolism in the hypothalamus with respective freely feeding (FF) controls and to monitor sex differences in RF-induced changes of 5-HT. RF decreased plasma tryptophan concentration in RF starved and RF fed females and also in RF starved males. In the hypothalamus tryptophan levels decreased in RF starved and RF fed female rats and RF fed males. 5-HT decreased in both RF starved and RF fed male and female rats and the decreases were comparable in the two sexes. 5-hydroxyindoleacetic acid (5-HIAA), a major metabolite of 5-HT was not affected. Food restriction decreased 5-HT concentration in the rest of the brain of male but not female rats. Possible implications of the findings in the pathogenesis of food restriction/starvation related disease anorexia nervosa and its greater occurrence in women than men is discussed. PMID- 11208457 TI - Activity of enzymes of adenyline compounds metabolism during crush and decompression of muscle tissue. Part II. Adenosine deaminase activity at experimental crush syndrome. AB - INTRODUCTION: Publications on investigation of crush syndrome pathogenesis, particularly of enzymatic systems upon traumatic toxicosis are rather limited. Such investigations are necessary for opportune diagnosis and definition of a treatment tactic. To replenish this deficiency, the adenosine deaminase level was studied in 12 rat tissues at experimental crush syndrome in vivo. RESULTS: The experimental model of crush syndrome on white rats was induced by crush and decompression of femoral muscle tissue. The crush syndrome influence on activity of adenosine deaminase isoenzymes was investigated in hemisphere, cerebellum, hypothalamus, pituitary body, heart, lung, liver, spleen, kidney, adrenal, as well as in crushed and native muscles. In 2 and 5 hours after compression, the enzyme activity decreased in muscles, lung and heart; increased in hypothalamus; remains near the control value in kidney and spleen. In cerebellum the parameter practically does not vary during 2 hours compression, while increased in 5 hours. In adrenal, liver, pituitary body and hemisphere the data after 5 hours compression approximated the level of control value in account of compensating mechanism. In 48 hours decompression after 2 hours crush, the adenosine deaminase activity becomes higher than control value in hemisphere, hypothalamus, cerebellum, liver, heart, adrenal, intact muscle, lung and kidney; in the crushed muscle and spleen the activity is reduced down to 60% of control value. In 48 hours decompression after 5 hours compression, the enzyme activity is higher than control value in hypothalamus, pituitary body, hemisphere, cerebellum, kidney, adrenal, heart and lung. The activity is reduced in muscles, spleen and liver. CONCLUSION: The level of adenosine deaminase in most of studied tissues differs from the control value depending on compression and decompression time. It is worthy of note that namely during decompression, the enzyme level deviates from the control in the majority of tissues. PMID- 11208458 TI - Influence of chronic cadmium exposure during pregnancy on DNA synthesis in different organs of rat offspring. AB - Though partly bound by placental metallothionein, cadmium easily enters fetal circulation and exerts toxic effects in offspring tissues and organs. The synthesis of DNA in different organs of rat offspring, whose dams were exposed to cadmium during pregnancy was examined in this study. Scintillation technique was applied for quantification of tritiated thymidine incorporation. In most studied organs a significant increase of DNA synthesis was noted, pronounced especially in small intestine and bone marrow (over 2-fold increase in comparison with controls). In view of known carcinogenic effects of cadmium in animals, our data suggest alteration of cell cycle in selected organs, which may correspond to increase of proliferation rate typical of neoplastic conditions. Further studies are necessary for correlating these findings with proliferation indices and expression of protooncogenes in situ. PMID- 11208459 TI - Attempt to identify hemolymph nodes in humans. AB - In the study, nodi limphatici pancreaticolienales obtained from 10 cadavers aged 30-70 years were analyzed. The death causes were other than proliferative diseases of lymphatic and hemopoietic systems, or gastrointestinal tract diseases. After fixation in Bouin fluid, dehydration and embedding in paraffin, 10 microns sections were prepared and subsequently stained with hematoxylin eosin. Additionally, hemosiderin reaction was performed on specimens from each analysed node. Positive hemosiderin reaction was found in none of the specimens. Certain theoretical aspects relating to hemolymph nodes were also presented in the paper. The authors conclude that there are no hemolymph nodes in the proximity of human splenic vessels. PMID- 11208460 TI - Helicobacter pylori, gastrin and cyclooxygenase-2 in lung cancer. AB - INTRODUCTION: Tumors arising in the lungs are in over 90% bronchogenic carcinomas that have been attributed predominantly to tobacco smoking, asbestos or air pollution but little is known about endogenous factors that could facilitate their development and invasiveness. The lungs originate embryologically from the same endoderm cells which form the epithelia lining the digestive tract, where gastrin is the major proliferative stimulus. AIMS: Since lung cancer patients were recruited mostly among smokers, who also have been found to exhibit significantly higher infection rate of Helicobacter pylori (HP) infection than non-smokers and, as since the HP-infected subjects show enhanced plasma levels of gastrin, we decided 1) to compare the seroprevalence of HP and the expression of its cytotoxin, CagA, in lung cancer patients with those in the age- and gender matched controls without cancer: 2) to determine the gene expression for gastrin and its receptors (CCKB-R) in lung cancer, 3) to assess the gastrin levels in plasma bronchial lavage and in tumor tissue and 4) to examine the expression of cyclooxygenase (COX)-1 and COX-2 in cancer tissue resection margin and intact bronchial mucosa. MATERIAL AND METHODS: The trial material included 50 patients with lung carcinoma and 100 age- and gender-matched controls. Anti-HP and anti CagA IgG seroprevalence was estimated by specific antisera using ELISA tests. Gene expression of gastrin, CCKB-R, COX-1 and COX-2 was examined using RT-PCR, while gastrin was measured by specific RIA. RESULTS: The seroprevalence of HP, especially that expressing CagA, is significantly higher in lung cancers than in healthy controls. Both gastrin and CCKB-R mRNA were detected in the cancer tissue and at the resection margin and similarly COX-2 mRNA was expressed in most cancers and resection margin but not in bronchial mucosa where only COX-1 was found. The lung cancer tissue and resection margin contained many folds larger amounts of immunoreactive gastrin than intact bronchial mucosa. PMID- 11208461 TI - Oleic acid serum phospholipid content is linked with the serum total- and LDL cholesterol in elderly subjects. AB - INTRODUCTION: Increased dietary intake of the olive oil has been found to lower several cardiovascular risk factors. Aim of our study was to check if there is any link between the oleic acid (OL-18:1n9) serum phospholipid (SPL) content and some of these factors in subjects living relatively far from the Mediterranean region and in habitual conditions, i.e. without any dietary intervention. MATERIAL AND METHODS: The investigated group included 62 out-patients older than 51 yr. Serum lipids were measured using standard hospital laboratory methods, the LDL-cholesterol was calculated using Friedewald's formula. Gas chromatography was used for estimation of fatty acids (FA) in SPL, their values were calculated as relative percentages of all FA. RESULTS: There was a statistically significant inverse correlation between the OL SPL content and the serum total cholesterol (TCHOL) in all 62 patients (r = -0.294; p = 0.020). Analogous correlation was marginally significant for the LDL (r = -0.245; p = 0.055). After a division into 2 groups based on the median of the OL, the group with OL higher than median had significantly lower both TCHOL and LDL (p = 0.014; p = 0.033, respectively). OL correlated positively with the alpha-linolenic acid (18:3n3; r = 0.281; p = 0.027) but inversely with the stearic acid (18:0; r = -0.303; p = 0.017). CONCLUSION: The subjects with less OL in their SPL had higher TCHOL and LDL serum levels and also their fatty acid SPL spectrum showed some other features which may be characterized as undesirable. This is an independent argument emphasizing the need for enhancing OL dietary intake. PMID- 11208462 TI - Evaluation of organ sparing surgery results in patients with kidney cancer in scheduled operations. AB - INTRODUCTION: The aim of the study was retrospective analysis of nephron-sparing surgery results of 53 patients, performed due to unilateral small kidney tumors in the period of 1988-1998. MATERIAL AND METHODS: The patients were followed-up according to EORTC directions for 20 to 143 months after the surgery. We have treated 25 women and 28 men of the average age of 53.7. In ten patients partial nephrectomy was performed and the remaining 43 had the tumor enucleated. RESULTS: The average observation time without any recurrences and metastases was 63.8 months, in 5.7% of patients local disease related recurrences and in 1.9% remote recurrences have been found. CONCLUSIONS: 1. Nephron-sparing surgery is a safe alternative to radical surgery in tumors of up to 4 cm in diameter. 2. Prospective 10-year survival time in our patients was 98%, including 92% of patients remaining without recurrence or metastases. 3. Positive prognostic factors are incidental diagnosis of a tumor and low staging and grading of a tumor. PMID- 11208463 TI - Interleukin-6 concentration in serum and cerebrospinal fluid in multiple sclerosis patients. AB - INTRODUCTION: The aim of the investigation was to determine pleiotropic cytokine IL-6 concentrations in serum and CSF of MS patients, with regard to clinical circumstances. MATERIAL AND METHODS: The study covered 27 MS patients: 23-51 years old; in the 2-7 clinical stage according to Kurtzke's Scale; mean 3.6 +/- 1.8; disease duration time ranged between 2-22 years. Serum and CSF interleukin-6 were determined by the use of commercial ELISA kits. RESULTS: Increase of Il-6 in serum of MS patients was found (12.1 +/- 1.8 pg/ml) in comparison to the control group (6.6 +/- 4.5 pg/ml) (p = 0.03). Concentration of IL-6 in CSF of MS patients was 13.4 +/- 1.77 pg/ml and in the majority of patients it was higher than in the serum. The highest mean of IL-6 concentrations in serum and CSF have been found in patients at the longer disease duration time, although there were not statistically significant. We have found some degree of dependence between serum IL-6 concentration and the level of disability in Kurtzke's scale. CONCLUSIONS: IL-6 participation in the basic MS immune processes is confirmed by its elevated concentration in serum and CSF, its relation to disease severity with the more expressed rise in cerebrospinal fluid. PMID- 11208464 TI - Concentration of s-ICAM-1 in nasal polyps tissue. AB - INTRODUCTION: Polyps are a nasal condition considered to be inflammatory in nature. Pathophysiology of that disorder is not fully known. The role of ICAM-1 in inflammatory and immune response through its involvement in leukocyte adhesion dependent phenomena is proved to be important. The aim of the study was to establish the role of sICAM-1 in the inflammatory process in nasal polyps. MATERIAL AND METHODS: 27 patients (23 males and 4 females) with nasal polyposis and 12 (7 males and 5 females) controls with septal deviation were included in the study. All patients underwent routine surgical treatment (polypectomy, septoplasty). The collected tissues of polyps and nasal mucosa were homogenized, placed in 0.04M EDTA and centrifuged. sICAM-1 concentration in supernatant of polyps and nasal mucosa tissue were determined with the ELISA method (Genzyme, UK). RESULTS: In the polyps tissue we found a significantly higher concentration of sICAM-1 compared to the nasal mucosa of healthy subjects (6.74 +/- 5.31 ng/ml vs 0.28 +/- 0.13 ng/ml; p < 0.001). The elevated concentration of sICAM-1 was positively correlated with total tissue eosinophil count (r = 0.51; p < 0.01) and the duration of the disease (r = 0.628; p < 0.001). No correlation was found between sICAM concentration and the age of the patients subjected to examination. CONCLUSIONS: The increased level of sICAM-1 in polyps tissue indicates the role of the molecule in the development of chronic inflammation and probably in the patophysiology of nasal polyps. PMID- 11208466 TI - Role of Chlamydia trachomatis in epididymitis. Part II: Clinical diagnosis. AB - The aim of the research was to analyse the complaints and symptoms in acute Chlamydia trachomatis (C.t.) epididymitis. The analysis of data from history and physical examination was made in dependence on detected Chlamydia infection in the group of 39 patients with the symptoms of acute epididymitis (1--12 men C.t. (+), 2--27 men C.t.(-)). Chlamydial epididymitis more commonly occurred in younger patients, and the symptoms of the disease persisted for a longer time than in the patients with epididymitis of another etiology. None of the men had suffered from nongonorrhoeal epididymitis before, while two of them (16.7 percent) had had urethritis. The difference in etiology was also reflected in the patients' complaints. The discharge from the urethra was more common in the patients with Chlamydia infection (1--58.3 percent, 2--18.5 percent) while epididymis oedema and scrotum erythema where twofold scarcer. No exact correlation between C.t. presence and leukocyte reaction intensity in urethra was noticed. The occurrence of chlamydial epididymitis is not always preceded by symptoms of urethritis and only in some cases they are accompanied by the increase of polynuclear leukocytes in urethral discharge. Chlamydial epididymitis is of milder course when compared to epididymitis of another etiology. PMID- 11208465 TI - Role of Chlamydia trachomatis in epididymitis. Part I: Direct and serologic diagnosis. AB - The aim of the study was to evaluate the role of Chlamydia trachomatis (C.t.) in the etiopathogenesis of epididymitis. 39 patients with symptoms of acute epididymitis were examined. They were divided into two age groups: 1st--patients aged below 35 (24 patients) and 2nd--patients older than 35 yrs (15 patients). The patients' urethral swabs were examined and C.t., mycoplasma and other Gram positive and Gram-negative bacteria were searched for as well as leukocyte count was assessed. Anti-Chlamydia trachomatis antibodies of IgG and IgM classes were assayed in serum. Direct immunofluorescence (antigen detection) and immunoenzymatic (antibodies detection) methods were used in C.t. infection diagnostics. C.t. infection in urethra was found in 30.8 percent of patients suffering from epididymitis, whereas in the control group in 2 percent. C.t. infection was significantly more commonly found in patients below 35 (45.8 percent) as compared with the older men (6.7 percent). The most common etiological factor in the younger group was C.t., while in the older group it was E. coli. IgG anti-C.t. antibodies were detected in the serum of 51.3 percent of the patients with acute epididymitis, as compared with 5.8 percent of the men in the control group. Specific IgG antibodies were found significantly more often in patients under 35 (66.7 percent) than in the older men (26.7 percent). Specific IgM antibodies were found in 15.4 percent of the patients, that is in 20.8 percent of the younger patients and in 6.7 percent of the older ones. C.t. is the main etiologic agent of epididymitis in men under 35. PMID- 11208467 TI - Analysis of the bacterial strains isolated from urine samples of hospitalized and ambulatory patients. AB - Bacteria of Enterococcus spp. are now much more often isolated from various diagnostic materials in systemic infection, both in hospitalized and in ambulatory patients. The study included 571 enterococci strains isolated from urine in 1997. Species identification was performed by rapid ID32 STREP test (bioMerieux) for 327 analyzed strains. Enterococcus faecalis and Enterococcus faecium dominated (46.1% and 11.2%, respectively). Over 42% of strains were isolated from urine of patients with non-significant bacteriuria or as concomitant flora. In such cases, simplified identification was performed and the strains were determined as Enterococcus spp. The microorganisms analyzed originated primarily from the urine samples of patients hospitalized at the Department of Urology (41.8%), the Department of Neurology (11.9%) and the Department of Internal Medicine and Nephrology (9.9%). Enterococcus faecalis strains were second with respect to population count (263--10.6%), after Escherichia coli strains (464--18.8%), while Enterococcus faecium strains were the sixth (64--2.5%). Enterococcus genus took the first place among all microorganisms isolated from the urine samples. Antibiotic-sensitivity was determined for 323 enterococci strains originating from hospitalized and ambulatory patients. Enterococcus faecium strains, naturally resistant to beta lactam antibiotics, were sensitive to nitrofuranoin in more than 50% and to norfloxacin in about 20%. Among 254 analyzed Enterococcus faecalis strains, 80.0% were sensitive to ampicillin, nitrofurantoin and high concentrations of gentamicin as well as streptomycin. Enterococci strains isolated from hospitalized patients proved sensitive to ampicillin and carbapenems in 76.8%, while strains isolated from ambulatory patients were 100% sensitive to these drugs. Examination of enterococci isolated from urine of patients hospitalized showed 33.8% sensitive to norfloxacin and 84.6% sensitive to nitrofurantoin. All the enterococci strains were sensitive to glycopeptide antibiotics: vancomycin, teicoplanin. PMID- 11208468 TI - Evaluating the profile of selected cytokines in patients with food allergy and chronic gastritis. AB - INTRODUCTION: Evaluating the profile of selected cytokines in patients with food allergy and chronic gastritis. Cytokines are produced by many cells and they play a role of mediators in the development of local and systemic inflammatory reaction. The aim of the study was to determine serum concentrations of IL-4, IL 5, IL-8, TNF alpha in patients with chronic gastritis and food allergy, who had been infected with H. pylori. MATERIAL AND METHODS: The study was conducted on patients with atopic diathesis, who were allergic to certain foods. The study group consisted of 71 patients, including 42 females aged 16-54 years (mean age 35.5 years) and 29 males aged 18-60 years (mean age 36.2 years). One control group was formed of 40 non-atopic patients aged 18-56 years (mean age 34.8 years), suffering from chronic gastritis. The other control group consisted of 30 subjects with the diagnosis of functional dyspepsia. Serum levels of selected cytokines were determined with the kits manufactured by ENDOGEN (Cambridge MA, USA) using enzyme immunoassay ELISA. The concentrations of parameters were determined in two tests and they were given as mean value. RESULTS: Mean serum Il 4 level in atopic patients was 27.85 pg/ml, while it was 13.26 pg/ml in non atopic subjects with chronic gastritis and 4.3 pg/ml in patients with functional dyspepsia. The concentration of IL-5 ranged between 0 and 111.3 pg/ml (mean value: 7.43 pg/ml) in subjects with food allergy. Comparative analysis of IL-4 and IL-5 concentrations in atopic patients and in control subjects showed the presence of statistically significant differences (p < 0.001). The remaining cytokines, i.e. IL-8 and TNF alpha showed a significant increase in serum levels in patients chronic gastritis when compared to the subjects with functional dyspepsia, without inflammatory changes. CONCLUSIONS: Chronic exposure of the patients with food allergy to a given food allergen makes the levels of IL-4 and IL-5 rise. In atopic subjects with chronic gastritis and H. pylori infection, the increase in IL-4, IL-5, IL-8 and TNF alpha levels suggests that both infectious and allergic factors play an important role in the pathogenesis of inflammation. PMID- 11208469 TI - Metabolic activity of neutrophils in patients suffering from chronic viral hepatitis. AB - The aim of the study was to evaluate the functional state of peripheral blood neutrophils in patients with chronic active viral hepatitis. Twenty-six patients with HBV, HCV or CMV in different clinical status were included in the analysis. In the study, the number of leukocytes and neutrophils was determined. The metabolic activity of neutrophils was examined in NBT reduction tests i.e. spontaneous (NBTsp) test and the one stimulated with LPS E. coli (NBTst). The results were analysed in relation to disease advancement and the type of viral infection. The data obtained from the affected patients were compared with the results from 46 healthy subjects. Most patients displayed neutropenia. It was found that the number of NBT positive cells and the coefficient of neutrophil metabolic activity (CNMA) in NBT sp test were highly significantly increased. The majority of patients had reduced values in NBTst test, which suggested lack of response to LPS E. coli by neutrophils. These findings may reflect the state of inflammation in the body. NBT reduction tests may be useful in monitoring metabolic activity of neutrophils in patients with chronic active viral hepatitis. PMID- 11208470 TI - Interferon alpha for eradication of HCV and remission of chronic hepatitis in children. AB - Thirty two children (8 girls and 32 boys), aged 4-14, with chronic hepatitis C were treated with interferon alpha at a dose of 3 MU or 5 MU, given times weekly for 6 months. Five children (16%) were complete responders (defined as disappearance of viremia), none of them relapsed, 6 (19%) were partial responders (normalization of ALT), 3 (9%) were transient responders (ALT initially decreased but then rebounded to pre-treatment levels) and 18 (56%) were non responders. During the treatment, continuous decrease of median ALT, AST and GGT was noted, statistically significant differences were found for comparisons of values measured before and after treatment (for ALT p = 0.023, for AST p = 0.021 and for GGT p = 0.012). Histological evaluation revealed one case of progression (to liver cirrhosis) out of three investigated complete responders, 1/5 such cases of partial responders, 1/2 of transient responders and 14/18 of non-responders. Remission of hepatitis was found in 2/18 (10%) non-responders. There was no statistically significant difference between 16 children previously infected with HBV (anti-HBc positive but HBsAg negative at the time of our study) and the others with respect to biochemical and histological severity of hepatitis or in the response to treatment rate. CONCLUSIONS: Chronic hepatitis C in children may cause severe hepatitis or even liver cirrhosis. Virological, biochemical and histological features should be considered to evaluate the severity of the disease and response to interferon treatment. Past infection with HBV does not affect interferon sensitivity in children with chronic hepatitis C. PMID- 11208471 TI - Atrioventricular septal defect: clinical and diagnostic problems in children hospitalised in 1993-1998. AB - INTRODUCTION: Atrioventricular septal defect (AVSD) is one of the most frequent congenital heart diseases, making up 7.5% of all developmental anomalies of circulatory system. MATERIAL AND METHODS: Sixty-seven children with the diagnosis of atrioventricular septal defect were hospitalised at the Department of Paediatric Cardiology, Medical University in Gdansk, in 1993-1998. Patients' age ranged at diagnosis between 3 days and 17 years (mean age 35 months). The analysed group included 20 children with partial atrioventricular septal defect (group I) and 47 children with complete AVSD (group II). The diagnosis was based on anamnesis, physical examination, ECG, chest x-ray and echocardiography. Cardiac catheterisation and angiocardiography were performed in 28 children. RESULTS: On the basis of the results obtained, 6 children with Down syndrome were disqualified from the surgery due to persistent pulmonary hypertension. Fifty nine children--including all the patients from group I (20) and 39 children from group II were qualified for operations in extracorporeal circulation. Two children from group II required ventilation with the mixture containing NO in the early post-operative period. There were 8 deaths (12%). Three children from group II died preoperatively due to severe generalised infection in early infancy and 5 infants from group II died immediately after operation. No deaths occurred in group I. In one case of a 4 year-old boy with partial atrioventricular septal defect, atrioventricular block developed immediately after surgery and required constant stimulation of the heart. In two children it was necessary to replace mitral valve (2 and 5 years after ASD I surgery). CONCLUSIONS: 1. Children with Down syndrome require screening echocardiography. 2. Non-invasive diagnostic examinations of atrioventricular septal defect are usually sufficient for the full assessment of the defect and the choice of further treatment. 3. The correction of the congenital heart disease such as atrioventricular septal defect should be completed in the first 6 months of life, particularly in children with complete AVSD. PMID- 11208472 TI - Blind liver biopsy in children--diagnostic significance and complications in authors' own material. AB - The purpose of the study is the analysis of liver biopsy performed in patients hospitalized at 3rd Department of Pediatric Diseases of Medical University in Bialystok in 1993-1998 with particular regard to the assessment of indications and the incidence of complications connected with the procedure. The procedure was conducted on the group of 250 patients aged 1-17 years with the use of Menghini needles. The indications for diagnostic liver puncture included chronic infection with HBV (228 children), chronic infection with HCV (6 children), chronic hypertransaminasemia (13 children), hepatomegaly (2 children) and hyperbilirubinemia (1 child). Complications were observed in 3 patients (1.2%). Blind liver biopsy is an important diagnostic tool in pediatric hepatology but possible occurrence of life-threatening complications suggests that it be used with caution. The paper was presented as a part of hepatological session of XXVI Congress of Polish Pediatricians in Mikolajki on 6-9th June 1999. PMID- 11208473 TI - Relationships between age-related changes of sex steroids, obesity and body fat distribution among healthy Polish males. AB - During the process of aging in males a trend toward an unfavourable body fat accumulation, especially within the visceral depots, is observed. This fact is presumed to be associated with the age-related decline in androgen levels among aging men. The aim of this study was to determine the relationships between sex steroid levels (DHEAS, estradiol, free and total testosterone) and BMI, percent fat mass, WHR values in 190 healthy and professionally active men, aged 22-67, inhabitants of the city of Wroclaw, Poland. Hormonal levels were measured using standard immunoassays. BMI was used as a measurement of obesity. Obesity was also assessed using percent fat mass equations according to the Crook formula. WHR was used as an index of fat distribution. All the correlations between sex steroids, BMI, WHR, percent fat mass and age were evaluated using statistical non parametric analyses (Spearman coefficient) in the entire group of examined subjects, and in two age-specific groups: a) younger males (aged 22-39) and b) older males (aged 40-67). The aging of Polish males is accompanied by both a significant increase of BMI, percent fat mass and WHR values, and by a decline in estradiol, gonadal and adrenal androgen levels. In the younger group only total testosterone levels were significantly negatively related to BMI, percent fat mass and WHR. Within the group of older men both estradiol and DHEAS levels are significantly positively related to WHR. The sex steroids seem to be associated with indices of overall obesity and distribution of fat in men, but these relationships differ considerably when they are evaluated in younger and older age categories. Worthy of notice is the fact that free testosterone levels are not related to any anthropometric parameters in any age category, although free testosterone (not total testosterone) is commonly recognised as a reliable and sensitive endocrinological indicator of the general psycho-physical status of an aging man. PMID- 11208475 TI - Kawasaki disease in an 18-month-old boy. AB - The authors present a case of Kawasaki disease with arrhythmia, aneurysms in the coronary vessels and disease recurrence in week 4. Despite late diagnosis, effective treatment with high doses of immunoglobulin and aspirin was introduced in the second week of the disease as well as during its relapse. PMID- 11208474 TI - Analysis of HBs antigen negative variant of hepatitis B virus: unique substitutions, Glu129 to Asp and Gly145 to Ala in the surface antigen gene. AB - We analyzed the surface gene (S gene) of a hepatitis B virus (HBV) isolate with mutations of envelope protein that rendered it undetectable by both a monoclonal hepatitis B surface antigen (HBsAg) enzyme-linked immunosorbent assay (ELISA) and polyclonal HBsAg radioimmunoassay (RIA). Sequencing of independently cloned products of HBV polymerase chain reaction revealed several point mutations within the S gene. Rare substitution was identified both at positions 129 (glutamine to asparagine) and at position 145 (glycine to alanine) in the 'a' determinant region, which is considered to be within a larger antigenic area known as the major hydrophilic region (MHR). A computer-assisted analysis of protein secondary structure could not find any significant difference between this mutant and wild type HBsAg. However, the substitution of substitution glycine to alanine at position 129 introduce a putative glycosylation site (Asn-Gly-Thr), which may interfere with the antigenicity of HbsAg. Also, HBV variant with substitution at position 145 (Gly to Ala) has been recently reported to be antigenically altered and to show impaired recognition by polyclonal hepatitis B hyperimmune globulin in vitro. These genetic mutations in the S gene inside MHR may allow to escape detection by standard HBsAg assays. PMID- 11208476 TI - Disseminated form of Langerhans cell histiocytosis discovered in stomatological examination--a case report. AB - Langerhans cell histiocytosis (LCH) is a disease involving formation of granulomatous infiltrations consisting of Langerhans cells, histiocytes, lymphocytes and eosinophilic granulocytes. Etiopathogenesis of this disease has not been fully clarified yet. It can present as a focal and disseminated form (acute and chronic). Rare incidence of this disease in the population causes progress in research and new therapeutic methods to be slow. Basing upon a case of a patient treated for gingivo-osseous lesions in the course of LCH, we tried to prove that a dental or maxillofacial surgeon may be the first contact medical professional who contributes to the diagnosis of LCH as a systemic disease. PMID- 11208477 TI - Congenital hypertrophic pyloric stenosis in twins. AB - The current report has been devoted to the presentation of the diagnosis and operative treatment of congenital hypertrophic pyloric stenosis in monozygotic twins. Special attention has been paid to a number of theories aiming to explain the aetiology and the mechanisms contributing to the development of congenital hypertrophic pyloric stenosis. PMID- 11208478 TI - Genetically determined coeliac disease in three family members. AB - The work presents 3 members of a family of 4, who were diagnosed to have coeliac disease (one classic and two latent forms of the disease). Genetic investigation regarding all three patients revealed the existence of HLA DQ A1*0501 allele associated with susceptibility to coeliac disease. Due to a much more frequent occurrence of atypical forms of coeliac disease in family members, than in general population, and due to risks resulting from tardy diagnoses and the lack of treatment, it is recommended that patients should be subjected to tests determining the presence of antiendomysial antibodies, as well as to genetic investigation with regards to latent coeliac disease. PMID- 11208479 TI - Imaging techniques in patients with biliary obstruction. AB - The most frequent causes of cholestasis include choledocholithiasis and neoplasms (pancreatic head carcinoma, ampullary carcinoma, cholangiocarcinoma). The authors discussed imaging modalities currently applied in the diagnostics of patients with suspected obstruction biliary tract obstruction. Special attention was paid to the efficacy of these techniques in detecting the obstruction and determining its level and nature. In general, US or CT are first performed in patients with cholestasis. The use of percutaneous cholangiography and retrograde cholangiopancreatography is often limited to therapeutic interventions. Magnetic resonance offers images similar to both conventional cholangiography and computed tomography. This technique offers complex evaluation of bile ducts and other abdominal organs. PMID- 11208480 TI - Macroscopic picture of gastric mucosa in endoscopic examination of patients with chronic gastritis and food allergy. AB - INTRODUCTION: The aim of the study was to evaluate the difference in macroscopic picture of the stomach in patients with food allergy and in non-atopic patients with H. pylori infection. MATERIAL AND METHODS: In the study, patients with atopic diathesis, suffering from dyspepsia or abdominal pain were analysed. The study group included 72 women aged 16-57 years (mean age 36.5 years) and 38 men aged 16 and 60 years (mean age 34.4 years). Control group was formed of 40 patients without atopy (13 men and 27 women, aged 18-56 years--mean age 34.8 years), with endoscopically and histologically confirmed gastritis. All the patients underwent endoscopy of upper gastrointestinal tract with the use of fiberoscope GIF-E OLYMPUS and video endoscopy monitor OEV 203 OLYMPUS (Japan). The following features of gastritis were considered in endoscopic assessment: oedema, reddening and fragility of mucous membrane, spotted and macular exudate, flat and raised erosions, proliferation and atrophy of mucosal folds, vascular network, intramural extravasation, mucosal structure. The results obtained were verified statistically with chi-squared independence tests for 2 x 2 tables. CONCLUSIONS: Statistical analysis of the incidence of these signs of inflammation in patients with food allergy did not show significant differences in relation to subjects with non-atopic gastritis. PMID- 11208481 TI - Melatonin and climactery. AB - Melatonin is a hormone synthesized in the pineal gland from tryptophan. It participates in several biological processes in the human being, such as circadian sleep rhythm, mood, reproductive processes and aging. Melatonin serum levels are increased in childhood and diminish importantly in older people. Serum levels are diminished in patients with insomnia and depressive mood. Experimentally, the melatonin inhibits the growth of mammary tumors in animals. With respect to endometrial cancer and Alzheimer's disease, the information is not conclusive. No changes have been found in melatonin levels in climacterical women. So its use has not fundament in postmenopausal women, however it can only be administered for short periods of time for the treatment of some sleep disturbances. PMID- 11208482 TI - Blood brain barrier and infection. AB - The blood brain barrier (BBB) is a highly dynamic structure and consists of endothelial cells, which are characterized by the presence of tight junctions and relative lack of endocytic vesicles. The tight junctions are reinforced by the foot processes of the astrocytes. The BBB functions through these specialised structures, to maintain the environment of the brain in a steady state by regulating the influx and efflux of substances. The protective effect of the BBB is however, lost during bacterial and viral infections. The primary mechanism operative are an increase in the permeability of the BBB and/or direct invasion of the brain by microorganisms. Since the BBB is relatively impermeable to chemotherapeutic agents the treatment of CNS infections is difficult. This paper aims to examine the various mechanisms by which infection spreads to the brain, and suggest measures for successful drug delivery into the brain during infections. PMID- 11208483 TI - Influence of the metabolic complications of liver cirrhosis on dietary intake. AB - The role of the nutrition is discussed in relation to chronic liver disease. An outline of the general principles involved in regulating nutrition in patients with advanced liver disease is given followed by an evaluation of the effects of malnutrition on the outcome of the disease. Major problems faced over the course of advanced liver disease are carbohydrate intolerance, sodium and fluid retention which may progress to hepatorenal syndrome, and hepatic encephalopathy. Interest on diet regulation in such cases has been recently reemphasized in multicenter studies particularly in the liver transplant setting and alcoholic liver disease. Controversies exist regarding albumin infusion after paracenthesis, low protein diet in hepatic encephalopathy and water restriction before sodium. The effect of nutrition on the outcome of liver disease and survival is not well established. However patients with better nutritional state do much better after transplant. PMID- 11208484 TI - What do we know about Kawasaki disease? AB - The authors present current theory of the aetiology and pathogenesis of Kawasaki disease with special reference to clinical presentation and cardiac complications. Current therapeutic management has also been discussed. PMID- 11208486 TI - Different sensitivity of mitochondrial and cytosolic monoamine oxidases to in vivo but not in vitro inhibition by specific irreversible inhibitors. AB - The sensitivity of mitochondrial and cytosolic monoamine oxidase (MAO) activities to inhibition by specific irreversible inhibitors was investigated. There were no significant differences in the sensitivity of MAO A and MAO B activities of these fractions to selective inhibitors. However, in vivo administration of pargyline caused a much more potent inhibition of cytosolic MAO than the mitochondrial enzymes. This suggests that cytosolic MAO activity does not represent an artifact (e.g. a product of proteolytic degradation) appearing after tissue homogenisation. The higher sensitivity of cytosolic MAO to inhibitors also points to different routes for pargyline to inhibit MAO in these subcellular fractions. PMID- 11208487 TI - Effect of polaprezinc on impaired healing of chronic gastric ulcers in adjuvant induced arthritic rats--role of insulin-like growth factors (IGF)-1. AB - Polaprezinc, N-(3-aminopropionyl)-L-histidinatozinc, has been shown to stimulate the production of insulin-like growth factor-1 (IGF-1) in mesenchymal cells, the polypeptide playing a role in the gastric epithelial wound repair. The present study was performed to examine the effect of polaprezinc on the impaired healing of chronic gastric ulcers in adjuvant-induced arthritic rats, in relation to IGF 1. Arthritis was induced in male Dark Agouti (DA) rats by a single injection of Freund's complete adjuvant (FCA), and the gastric ulcers were induced by thermal cauterization (70 degrees C for 30 sec) 7 days after FCA injection. Omeprazole (30 mg/kg) was administered p.o. once daily, while recombinant human IGF-1 (rhIGF 1) (30 micrograms/kg, s.c.) or polaprezinc (3-10 mg/kg, p.o.) was administered twice daily, starting from 3 days after ulceration for 14 days. The healing of gastric ulcers was significantly delayed in arthritic rats as compared to normal rats on day 10 and 17 following ulceration. The expression of IGF-1 mRNA was markedly increased in the ulcerated mucosa, but this response was apparently attenuated in arthritic rats. Repeated administration of polaprezinc accelerated the healing of gastric ulcers in both normal and arthritic rats, in a dose dependent manner, and this effect was more pronounced in arthritic rats. Likewise, treatment with omeprazole also significantly promoted the healing of gastric ulcers in both normal and arthritic rats. On the other hand, rhIGF-1 significantly promoted the gastric ulcer healing in arthritic rats without any effect on that in normal rats. These results suggest that the impaired healing of chronic gastric ulcers in arthritic rats is, at least partly, accounted for by less expression of IGF-1, and the polaprezinc improves the delayed healing of gastric ulcers in arthritic rats, probably through an increase in IGF-1 production. PMID- 11208485 TI - Significance of endothelial prostacyclin and nitric oxide in peripheral and pulmonary circulation. AB - BACKGROUND: Vasoprotective function of endothelial cells is associated, among others, with biosynthesis and release of nitric oxide (NO), prostacyclin (PGI2), prostaglandin E2 (PGE2), carbon monoxide (CO) and plasminogen activator (t-PA). These endothelial mediators calm down activated platelets and leukocytes, prevent the occurrence of parietal thrombotic events, promote thrombolysis, maintain tissue perfusion and protect vascular wall against acute damage and against chronic remodeling. Endothelial dysfunction in patients suffering from atherosclerosis or diabetes type 2 is associated not only with suppression in release of the above mediators but also with deleterious discharge of prostaglandin endoperoxides (PGH2, PGG2), superoxide anion (O2-, peroxynitrite (ONOO-), and plasminogen activator inhibitor (PAI-1). We looked for mechanisms of protective endothelial function, with a special respect to the differences between peripheral and pulmonary circulation. METHODS: Cultured endothelial cells of bovine aorta (BAEC) were used to study physiological and pharmacological mechanisms of increasing free cytoplasmic calcium [Ca2+]i. A porphyrinic sensor quantified the release of NO from BAEC. In cultured human umbilical vein endothelial cells (HUVEC) we looked for induction by bradykinin (Bk) of mRNAs for a number of enzymes. In blood perfused rat lungs we studied protective role of NO against injury inferred by lipopolysaccharide on pulmonary microcirculation that was accomplished by thromboxane A2 (TXA2), platelet activating factor (PAF), cysteinyl-leukotrienes (cyst-LTs) and the complement system. In vivo we analyzed the influence of Bk, perindopril and quinapril ('tissue type' angiotensin converting enzyme inhibitors, ACE-Is) on endothelial function in entire circulation of anaesthetized rats using a thrombolytic bioassay and EIA for 6 keto-PGF1 alpha and t-PA antigen. RESULTS: In BAEC Bk via kinin B2 receptors raised in a concentration-dependent manner (1 pM-10 nM) free cytoplasmic calcium ions [Ca2+]i, that triggered the release of NO from BAEC. Calcium ionophore (A23187, 1-100 nM) as well as receptor agonists such as adenosine diphosphate (ADP, 10 nM-1 microM), adrenaline (Adr, 1-10 microM) or acetylcholine (Ach, 10 100 microM) produced a similar rise in endothelial [Ca2+]i as did Bk at a nanomolar concentration. 'Tissue type' ACE-Is, e.g. quinapril or perindopril acted through accumulation of endogenous Bk. However, the potency of ACE-I to change endothelial function is by several orders of magnitude lower than that for exogenous Bk. In vivo the major difference between thrombolytic actions by quinapril or perindopril on one hand, and by exogenous Bk on the other was longevity of thrombolysis by ACE I and a distinct hypotensive action of exogenous Bk. Still, the long-lasting isolated thrombolytic effect of ACE I was mediated entirely by endogenous BK as evidenced by the preventive action of icatibant, a kinin B2 receptor antagonist. Moreover, in vivo the immediate thrombolysis by ACE I was mediated by PGI2 rather than by NO or t-PA, as shown by pharmacological analysis, and by direct blood assays of 6-keto-PGF1 alpha and t-PA antigen. Bradykinin as a mediator of pleiotropic endothelial action of several cardiovascular drugs (e.g. ACE-I) may complete its mission not only through B2 receptor and [Ca2+]i--mediated release of PGI2 or NO. Here, we describe a new route of the Bk action. Bk mediated induction of the [Ca2+]i-independent, so called 'inducible', endothelial isoenzymes required for generation of CO, PGI2 and PGE2. After 4 hours of incubation of HUVEC with Bk (10 nM) it induced mRNAs for haemooxygenase 1 (HO-1), cyclooxygenase 2 (COX-2), prostaglandin E synthase (PGE-S) whereas mRNA for nitric oxide synthase 2 (NOS-2) was weakly affected. We proved also that unlike in peripheral circulation, in pulmonary circulation only NO but not PGI2 would play a protective role. In the blood-perfused lung, endotoxaemia liberates lipids, such as TXA2, PAF and cyst-LTs. These toxic lipids along with the activated complement mediate pulmonary damage. Pulmonary endothelial nitric oxide is the only local protector against lung injury evoked by the phagocytised bacterial lipopolysaccharide. SUMMARY: Summing up, in peripheral circulation endogenous Bk is the most efficient activator of protective endothelial function. For instance, thrombolytic action of 'tissue type' ACE-I depends on the Bk-released PGI2. Acting as an agonist of endothelial B2 kinin receptors Bk rises [Ca2+]i with a subsequent activation of constitutive COX 1 and NOS-3. This is followed by an immediate release of PGI2 and NO. Moreover, acting as 'microcytokine' Bk induces mRNAs for HO-1, COX-2 and PGE S, the isoenzymes responsible for a delayed endothelial biosynthesis of CO, PGI2 and PGE2. (ABSTRACT TRUNCATED) PMID- 11208488 TI - Stoppage of blood flow in 3-methylcholanthrene-induced autochthonous primary tumor due to a novel combretastatin A-4 derivative, AC7700, and its antitumor effect. AB - BACKGROUND: Using several transplanted tumors in rats and mice, we have recently shown that the acute extensive necrosis of tumor nodules is caused by the systemic administration of AC7700, a novel combretastatin A-4 derivative, and that the necrosis can be attributed to irreversible stoppage of tumor blood flow (TBF). In this study, the antivascular and antitumor effects of AC7700 were tested on primary autochthonous tumor. MATERIAL AND METHODS: Primary sarcomas were induced in Fischer F344 rats by a single s.c. inoculation of 3 methylcholanthrene (MC) (4 mg/0.5 ml/head). Changes in TBF due to AC7700 were measured by hydrogen clearance technique. Antitumor effects of AC7700 were evaluated by histology and tumor growth inhibition. RESULTS: The earliest primary tumor appeared 77 days after MC treatment and the last tumor appeared after 273 days (median, 140 days). Once tumors occurred, they continued to grow slowly and never regressed spontaneously. The mean doubling time of tumors (n = 34) during exponential growth was 12.6 +/- 9.0 days (mean +/- SD) (range, 5.4-55.9 days). Blood flow in these slow-growing autochthonous tumors decreased highly significantly from 25.2 +/- 15.5 to 4.4 +/- 3.2 ml/min/100 g (24 electrodes)(P < 0.001) within 30 min due to rapid i.v. injection (0.15 ml/min) of 10 mg/kg AC7700 and the decreased TBF did not recover during the experimental period of 6 h. On the other hand, TBF did not change significantly due to 0.9% NaCl solution (10 electrodes). In addition, TBF immediately began to decrease following slow infusion (0.005 ml/min) of 10 mg/kg AC7700 and decreased by approximately 80% (12 electrodes) at 20 min after the start of AC7700 infusion. To evaluate the antitumor effect of AC7700 on the primary tumors, 10 mg/kg AC7700 was injected i.v. to tumor-bearing rats. Although in the natural course, such tumors never stop growing, the tumor growth was strongly inhibited by AC700 (n = 5). In 2 cases, tumors never regrew for the observation period of 45 days. Biopsy and histological findings (n = 5) showed that tumors underwent extensive necrosis, as was observed previously for transplanted tumors following AC7700 administration. CONCLUSION: From the present experiment it was demonstrated not only in transplanted tumors but also in carcinogen-induced autochthonous primary tumors that acute and sustained stoppage of TBF led to strong antitumor effects. The novel anticancer compound AC7700 might become a very useful therapeutic strategy against refractory cancers. PMID- 11208489 TI - Contractility of smooth muscles and ultrastructure of their microfilaments in restriction of physical activity. AB - BACKGROUND: Depending on the intensity of hypodynamics (as a factor of ischemic heart disease) the aim of our investigation was to determine the contractility of smooth muscles of thoracic aorta with and without endothelium by biological active substances (prostaglandin F2 alpha and acetylcholine) and to compare with ultrastructural alterations of microfilaments. MATERIAL AND METHODS: A hypodynamic stress of 48-days duration was provoked via permanent and periodically recurrent intervention (when the hypodynamic state was altered with physical activity) in Chinchilla rabbits by placing them in metal hutches (according to B. M. Fiodorov). The relaxing effect of endothelium--dependent vasodilatator agonist (acetylcholine in concentration 10(-7) M, 10(-6) M, 10(-5) M, 10(-4) M) on smooth muscles (treated with vasoconstrictor prostaglandin F2 alpha) was detected by means of a mechanotron 6 MXIC in isometric regime. The contraction force was expressed in percentage. One hundred percent was the maximum contraction that developed after administration of 2 x 10(-5) M prostaglandin F2 alpha solution to the smooth muscles preparation. For ultrastructure studies of microfilaments semithin sections of smooth muscles were examined with electron microscope 'Philips--300'. RESULTS: The research findings show that under the influence of acetylcholine the relaxing of endothelium of thoracic aorta smooth muscles (treated with prostaglandin F2 alpha) is more expressed in periodically recurrent intervention. CONCLUSION: Permanent hypodynamic stress of 48 days duration caused strongly expressed contractility of smooth muscles with is associated with ultrastructural damage of microfilaments (such as irregular formation, drop out in flakes, microfilaments becoming shorter and thicker). PMID- 11208490 TI - Tirilazad mesylate improve water immersion stress induced decrease in erythrocyte deformability in the rats. AB - BACKGROUND: Water immersion stress (WIS) in rats causes decrease in deformability of red blood cells (RBC). We hypothesize that this phenomenon is mediated by reactive oxygen species. Since tirilazad mesylate (U74006F) is a potent scavenger of free oxygen radicals, the aim of this study was to investigate possible influence of this drug on WIS induced decrease in RBC deformability in rats. MATERIAL AND METHODS: The rats were injected i.p. with tirilazad mesylate in a dose of 10 mg per kg body weight or vehiculum at the beginning of the experiment and immersed in water at 23 degrees C to the depth of xyphoid for 5 h. Control rats were kept in normal environment. After 6 h blood samples were collected for examination. An elongation index of RBC measured by Rheodyn SSD (Myrenne GmbH, Germany) was used as a parameter of deformability. Lipid peroxidation products have been assayed in RBC by BIOXYTECH LPO-586 kit. RESULTS: Tirilazad mesylate prevents a decrease in RBC deformability, but does not prevent an increase in concentration of lipid peroxidation products in erythrocytes during WIS. CONCLUSION: Positive effect of tirilazad on stress induced decrease in RBC deformability is not related to inhibition of lipid peroxidation within the erythrocytes. PMID- 11208491 TI - Heparin-induced modulation of insulin like-growth factor-I action on glucose level in control and fasted rats. AB - BACKGROUND: Insulin like-growth factor-I (IGF-I) circulates in serum bound to IGF binding proteins (IGFBPs), which are important regulators of IGF's biological activity. There are at least two classes of BPs: a high molecular weight complex (HMWBPs) and low molecular weight species (LMWBPs), with different affinity for IGF-I. Their specific role in regulation of IGF-I bioactivity is still controversial. Since: a) IGF-I plays an important role in glucose counter regulation; b) heparin was shown to alter IGF-I affinity to BPs; and c) fasting is known to change quantity and quality of serum BPs, we decided to measure the in vivo effect of heparin on blood IGF-I, BPs and glucose levels in control and fasted rats. MATERIALS AND METHODS: Control and fasted rats were injected i.v. with heparin (500 UI/100 g body weight) every hour during 3 hours of the experiment. Blood samples were collected before and 15 or 30 minutes after heparin injection and used for determination of free and bound IGF-I (RIA), BPs (radiometric assay) and glucose level (glucose oxidase method). RESULTS: Heparin treatment induced hypoglycaemia in fasted rats while it induced hyperglycemia in control one. The evidence was provided that heparin dissociates IGF-I from HMWBPs complex of control rat serum (predominant one in serum of these animals) and released IGF-I in turn is bound to LMWBPs--known as inhibitors of IGF-I dependent functions. In contrast, in fasted rat serum heparin dissociates IGF-I from LMWBPs (predominant complex in serum of these animals) making IGF-I free and available to stimulate IGF-I dependent functions. Therefore in control animals, which were administered heparin, blood glucose level was elevated and in fasted animals it was decreased. CONCLUSIONS: The data presented raise the possibility that IGF-BPs may have an important role in IGF-dependent glucose counter regulation and that heparin or heparin-like molecules may affect the process. Medical significance of heparin-induced hyperglycaemia in control animals should be taken into consideration since heparin is commonly used in clinical practice. PMID- 11208492 TI - The changes of alpha-amylase activity in serum and different tissues of female rat during sex cycle--isoelectrofocusing studies of alpha-amylase. AB - BACKGROUND: It has been suggested that hormonal changes may influence alpha amylase activity during sex cycle. The aim of this study was to evaluate these changes in serum and different tissues during sex cycle in female rats. MATERIAL AND METHODS: The animals were assigned to proestrus, estrus, and diestrus groups depending on vaginal smears. We measured the activities of alpha-amylase in the serum, liver, salivary glands, pancreas and ovary of female rats, serum level of calcium, rat luteinising hormone (rLH) and rat follicle stimulating hormone (rFSH). The serum and tissue amylases were also characterized by wide-range polyacrylamide gel isoelectrofocusing. RESULTS: Statistically significant changes of alpha-amylase activity were found only in the ovary. The activity of alpha amylase raised from proestrus (mean 303 +/- 124 IU/g) through estrus (mean 157 +/ 123 IU/g) and declined in diestrus (mean 81.9 +/- 51.6 IU/g). There were no statistically significant changes in the serum, liver, salivary glands and pancreas. We found two isoenzymes of alpha-amylase: one peak of amylase, present in the serum, liver, salivary gland and ovary with the mean isoelectric point of ca 5.34 and another present in ovary and pancreas with mean isoelectric point of ca 8.32. The only tissue found to contain both isoamylases was the ovary. We did not find any correlation between serum calcium level and alpha-amylase activity in the serum and ovary. CONCLUSION: The pattern of changes of alpha-amylase activity does not depend on the type of isoamylase in the tissue, but probably on the tissue influenced by the sex cycle. The changes of alpha-amylase activity are not mediated by calcium, they seem to result primarily from the profile of sex hormones affecting directly the target tissues. PMID- 11208493 TI - Changes in serum concentrations of markers of myocardial injury following treadmill exercise testing in patients with suspected ischaemic heart disease. AB - BACKGROUND: The treadmill exercise test (TEST) is frequently used in patients with suspected ischaemic heart disease to establish a diagnosis and estimate future risk. However, its predictive value is poor. We aimed to investigate whether measurement of biochemical markers of myocardial injury could improve the diagnostic value of the procedure. MATERIAL AND METHODS: Twenty-four subjects with suspected acute coronary syndrome underwent a treadmill exercise stress test. Of these 13 had had a previous myocardial infarction and two had a past history of coronary artery bypass grafting. Nine subjects were found to be positive for coronary ischaemia during the treadmill test. Serum cardiac markers (total creatine kinase [CK], CK-MB, Troponin I and Troponin T) were measured pre TEST, and 0, 1, 2, 4, 8 and 24 hours following the treadmill test. RESULTS: Total CK remained within the reference range for all subjects and showed no significant rise. However, mean serum concentrations of CK-MB were significantly higher than pre-test values at 2 hours (p < 0.03) following treadmill exercise testing in subjects who had a positive exercise stress test, but not in those with a negative test. In the subjects with a positive stress test, CK-MB levels returned to pre-Test value by 24 hours. Levels of neither serum troponin I, nor troponin T altered significantly at any point. CONCLUSION: The measurement of CK-MB, but not cardiac troponins may add to the diagnostic utility of the TEST. PMID- 11208494 TI - Power spectral components of heart rate variability in different types of cardiac remodelling in hypertensive patients. AB - BACKGROUND: The aim of the study was to evaluate whether there are any significant differences in cardiac autonomic regulation in distinct types of hypertensive cardiac remodelling. MATERIAL AND METHODS: We examined 86 patients with mild to moderate essential hypertension (EH). The parameters of left ventricle (LV) were measured by echocardiography: the diastolic mass normalized for body surface area (LVMI) and relative wall thickness (RWT). All patients were divided into three groups: normal LV geometry (23), concentric left ventricular hypertrophy (LVH) (29) and eccentric LVH (34). The control group included 30 age and sex-matched healthy volunteers. For calculation of heart rate variability (HRV) 512 RR intervals in supine rest and passive tilt were measured. Power spectral analysis with fast Furrier transform was used to obtain the total power, low frequency (LF) power (from 0.003 to 0.14 Hz), high frequency (HF) power (from 0.15 to 0.40 Hz) and sympathovagal index (SVI) as LF:HF ratio. RESULTS: The parameters of HRV did not differ significantly among the groups studied. In the group with normal LV geometry there was observed a good response to tilt test resulting in an increase of SVI in three times (from 2.4 +/- 0.3 to 7.2 +/- 0.4), while in patients with both types of LVH there were no significant changes in SVI or even an inverse reaction to passive tilt. In the group with normal geometry patients with higher meanings of RWT had higher LF power (r = 0.52, p < 0.01), while in patients with LVH the increasement of LVMI and RWT was associated with reduction of HRV (rr = -0.43, -0.36, p < 0.05, respectively). CONCLUSIONS: Heart rate variability is significantly reduced in essential hypertension and is also closely connected with cardiac structure and function. Patients with normal LV geometry are characterized by a preserved response to tilt test. LVH produce significant disturbances of autonomic regulation possibly due to lower sensitivity of cardiac adrenoreceptors independently of the LVH pattern. PMID- 11208495 TI - Sudden rate drop intervention rate level in patients with new 'clarity' pacemakers and carotid sinus syndrome. AB - BACKGROUND: In patients in whom syncopal episodes are mainly caused by occasional drops in heart rate, Sudden Rate Drop intervention feature intends to provide high rate intervention pacing. New Vitatron Medical B.V. pacemaker system Clarity DDDR, provides AN option FOR recognizing Sudden Rate Drop and responding by intervention pacing until it detects the recovering. MATERIAL AND METHODS: In patients with carotid sinus syndrome it is possible to provoke this situation BY sinus carotidus massage. We have implanted 10 of these devices in our center, 2 of which in patients with hypersensitive carotid sinus syndrome. In both patients, we activated sudden rate drop intervention on DDD mode pacing and applied protocol for testing the necessary level of Sudden Rate Drop Intervention Rate. Both patients gave their informed consent to be submitted to this testing. Pacemaker software assumes rate intervention level of 110 bpm. We tested our patients for rate levels of 90 and 110 bpm. Massaging the carotid sinus during 5 seconds, we provoked Sudden Rate Drop Intervention 10 times, in each patient, 5 times at intervention rate of 90 and 5 times at 110 bpm. Patients were unaware of the programmed intervention rate and were merely expected to report any different sensations experienced during the testing. RESULTS: In all 20 tests, pacemaker responded to sudden rate drop elicited by carotid sinus massage (100%), which was verified by selected event recordings. After the massage, neither of the patients registered any sensations at sudden rate drop intervention rate level of 90 bpm in a total od 10 tests (100%), while 8 out of 10 massages at 110 bpm intervention rate provoked palpitations (80%). On the grounds of this testing, we concluded that lowering of Sudden Rate Drop Intervention Rate Level from 110 BPM to 90 BPM does not affect the reliability of system reaction, but changes patient's awareness of heart beats. CONCLUSION: As a final conclusion, it should be said that basic prerogatives of a pacing system: safety and efficacy with minimal energy consumption, and in this case, quality of life option that a patients practically does not feel intervention when it occurs, are all met. PMID- 11208496 TI - Efficacy of sequential antiarrhythmic treatment in sinus rhythm maintenance after successful electrocardioversion in patients with chronic non-valvular atrial fibrillation. AB - BACKGROUND: Sequential use of antiarrhythmic drugs may improve prognosis in chronic atrial fibrillation (AF). We conducted a prospective study of the efficacy of sequential antiarrhythmic drug therapy in sinus rhythm (SR) maintenance after a successful electrocardioversion (CV) in pts with chronic AF. MATERIAL AND METHODS: 58 pts (64.3 +/- 4.3 years old) with chronic AF underwent CV. After SR restoration (Group I) pts received one of the following antiarrhythmic drugs (Drug I): propafenone, sotalol or disopyramide. In case of arrhythmia recurrence, second CV was performed and pts received another drug from those mentioned above (Drug II). If treatment proved to be unsuccessful pts received amiodarone (Drug III) and third CV was attempted. After first unsuccessful CV (Group II) pts received a loading dose of amiodarone and another CV was attempted. In case of SR restoration amiodarone was administered continuously. RESULTS: After 12 months 81% pts were on SR; 85% pts received amiodarone continuously. After 1 year 6 (10%) pts presented with SR treated with Drug I (median 71 days); Drug II proved to be ineffective in all patients (median 27 days). 28 pts continued to receive amiodarone (no median). CONCLUSIONS: Sequential antiarrhythmic drug therapy improves arrhythmia prognosis in AF within a 12-month observation period. Amiodarone seems to be the most effective antiarrhythmic drug also in pts who required second CV proceeded by amiodarone treatment to restore SR. PMID- 11208497 TI - Effects of the T-type calcium channel blockade with oral mibefradil on the electrophysiologic properties of the human heart. AB - BACKGROUND: As the calcium T-channel blockade is a new pharmacological category with presumably unique electrophysiological effects, the influence of its only representative yet mibefradil was tested after the single oral dose. MATERIAL AND METHODS: 10 patients underwent the electrophysiologic examination. Normal baseline values in sinus node cycle length (SNCL), sinus node recovery time (SNRT), corrected sinus node recovery time (CSNRT), PA interval, atrial effective refractory period, AH interval, Wenckebach point (WP), atrioventricular nodal refractory period, and HV interval were measured using standard techniques. After that a single dose of 100 mg mibefradil was given and the testing repeated in 90 minutes. RESULTS: Though non-significantly in a study-group limited in size due to global withdrawal of mibefradil, sinus node automaticity was suppressed (prolongation of SNRT by 5.1% and CSNRT by 11.5%) and heart rate lowered (SNCL prolonged by 2.8%) comparatively more than was the negative dromotropic effect on the atrioventricular node (negligible prolongation of AH interval by 1.1% and WP cycle by 0.4%). CONCLUSIONS: Demonstrated electrophysiological effects of oral mibefradil with more pronounced influence on the automaticity of the sinus node seem to be in agreement with the preclinical data on the predominant role of T channels in the pacemaker activity of the sinus node. According to the Framingham data on the risk of heart rate for the cardiovascular as well as all-cause mortality, calcium T-channel blockade offers a desirable profile for antihypertensive treatment. From this point of view development of new representatives of calcium T-channel blockers could be a useful contribution to clinical practice. PMID- 11208498 TI - Statistical dependence of clinical data on the chosen treatment of patients with a multivessel coronary artery disease. AB - BACKGROUND: In this study we tried to check which clinical data are connected with the choice of treatment in patients with a multivessel coronary artery disease. MATERIAL AND METHODS: The data of 137 patients with a multivessel coronary artery disease, were analysed retrospectively. The patients were divided into three groups: treated conservatively, CABG and PTCA. Multivessel coronary artery disease was recognised when there were atherosclerotic changes in more a 2 vessels with a not less a 2 mm in diameter. Patients with previous CABG or a left main coronary artery disease were excluded. The data were analysed by means of several methods, variance analysis, correlation analysis, discriminant functions, chi-square test and T-Student test. RESULTS: For treatment decision making in multivessel coronary artery disease of statistical significance were: the state of the left anterior descendent artery below the first diagonal branch, the state of the first diagonal branch and peripheral parts of the left anterior descendent artery and right coronary artery, the systolic function of the antero-lateral, apical and phrenic segments of the left ventricle, the global left ventricular ejection fraction in angiography and echocardiography, local systolic disturbances of the left ventricular observed in echocardiography, the coexistence of symptoms of heart failure as well as unstable angina. CONCLUSION: Treatment decision making will always depend not only on diagnostic procedures but also on all the clinical data about the patient and the experience of coworking cardiology and surgery centres. PMID- 11208499 TI - Cholecystitis, gallstones and free radical reactions in human gallbladder. AB - BACKGROUND: The relationship between biophysical and biochemical processes of gallbladder bile and free radical reactions is still not known. The aim of our study was to investigate the correlation between free radical production and the degree of inflammation in gallbladder. MATERIAL AND METHODS: The degree of chronic cholecystitis was determined by observing the number of infiltrating lymphocytes and the mucosal epithelial change. The free radical reaction products were determined by measuring the chemiluminescent light intensity, the malondialdehyde (MDA) and dien concentration of bile. RESULTS: The content of free radical reaction products, like MDA and diene in bile slightly decreased with the severity of cholecystitis. The size of stones inversely correlated with the severity of inflammation. The chemiluminescent light intensity showed correlation with bilirubin concentration. Between 501 (mol/l range the bilirubin gave significantly higher chemiluminescent light intensity, than in the lower and in the higher concentration range. In this bilirubin concentration range diene concentration correlated inversely with chemiluminescent light intensity, while MDA concentration elevated with the bilirubin concentration. CONCLUSION: Correlation was found between the number of stones and the degree of cholecystitis which may indicate that free radical products are incorporated into the stones and do not stay in solution. The high chemiluminescent light intensity of the bile at the 501-1300 (mol/l bilirubin concentration range means that bilirubin participates at this concentration most reactively in free radical reactions. These results suggest, that there is a correlation between free radical reactions, gallstone formation and the degree of cholecystitis. PMID- 11208500 TI - Level of malondialdehyde after short-time omeprazole administration. AB - BACKGROUND: Omeprazole is a proton pump inhibitor of increasingly wide application in the treatment of different gastroenterological diseases. The purpose of the study was to evaluate the effect of omeprazole (O) on the level of plasma malondialdehyde (MDA). MATERIAL AND METHODS: Omeprazole was administered intraperitoneally to male Wistar rats twice a day, for 3 days, in two doses: O1 0.57 mg/kg body weight (b.w.), O2-5.71 mg/kg b.w. Twelve hours after the last injection half of the animals were terminated (I). The remaining rats were kept for the next 6 weeks without any xenobiotics (II). The blood was taken from the still beating heart and then centrifuged. The plasma level of MDA was determined and compared to the 1 mg of the blood protein. RESULTS: A significant (p < 0.05) increase of MDA level was found in the O2II group, as compared with the O2I group. The level of MDA was higher after 6 weeks' period in relation to the animals that were terminated on the 4th day of the experiment. CONCLUSION: Three day omeprazole administration did not change the MDA level in the rat plasma. PMID- 11208501 TI - Effect of immunosuppressive cladribine treatment on serum leucocytes system in two-year clinical trial in patients with chronic progressive multiple sclerosis. AB - BACKGROUND: Multiple sclerosis is presumably cell-mediated autoimmune disorder with immune abnormalities as presence of activated T-cells and increase interleukin 2 (IL-2) and soluble IL-2 receptor (sIL-2R) levels in central nervous system and peripheral blood of patients. The aim of immunosuppressive treatment is to diminish such activation. The aim of this study was to evaluate the influence of immunosuppressive cladribine treatment with total dose of 2.1 mg/kg b.w. administered in 7 cycles for 12 months, on serum leucocytes in 34 chronic progressive multiple sclerosis (CPMS) patients observed for 2 years as well as IL 2 and sIL-2R serum levels assessed before and right after the treatment. MATERIAL AND METHODS: The study was designed as a randomised, placebo-controlled, double blind trial. The patients were divided in two groups: group I, cladribine treated, n = 34; group II, placebo-treated, n = 35. Group III were healthy controls, n = 20. Leucocyte levels were determined with flow-cytometry. IL-2 and sIL-2R levels were assessed with enzyme-linked immunosorbent assay. RESULTS: Statistically significant gradual decrease of lymphocyte level was observed from 7th week to 12th month after the beginning of treatment. During the following 12 months, lymphocyte levels remained decreased in comparison to baseline. Mean values of IL-2 and sIL-2R levels measured 12 months after the treatment were found to be lowered by 20% (p. = 0.01) and by 24% (p. = 0.0005), respectively. CONCLUSION: The results obtained indicate fast and long-lasting decrease of serum leucocyte level and suppressive influence of cladribine treatment on immune processes in multiple sclerosis patients. PMID- 11208502 TI - Immunological investigation in children with juvenile chronic arthritis. AB - BACKGROUND: Immunological investigation is a part of the complex view on a child with juvenile chronic arthritis (JCA). We analyzed the data of a cohort of children with JCA in order to determine the real contribution of this investigation to their diagnosis and therapy. MATERIAL AND METHODS: We included the investigation of humoral immunity and autoantibodies of 78 children with JCA. 18 children completed investigation of both humoral and cellular immunity of paired peripheral blood (PB) and synovial fluid (SF). Humoral immunity consisted from immunoglobulins, complement, circulating immune complexes, rheumatoid factors, soluble HLA I. molecules and antinuclear and antineutrophil cytoplasmic antibodies. Cellular immunity included cytometric studies of CD3, CD4, CD8, CD16/CD56, CD19, CD20, 23, CD3 HLA DR+, CD45 RA, CD45 RO, alpha/beta and gamma/delta T cells. To observe the status of Th1/Th2 balance in children with JCA, the cytokines IL-4, IFN gamma, TNF alpha and IL-6 were measured in the tissue culture of the synovial cells. RESULTS: The parameters of humoral immunity in serum showed wide variability. We could not confirm particular changes specific for the forms or stage of the disease. ANCA were positive in 21 out of 78 children with JCA, 3 times both in PB and SF. More typical pattern could be followed in the comparison of PB and SF, with immunoglobulins and complement always found lower in SF than in PB. The cellular immunity was represented by the activation of lymphocytes mainly in SF, reverse ratio of CD45 RA and RO cells in PB and SF with marked predominance of memory T cells in the joint. High levels of sHLA in SF are the nonspecific marker of activation, the same is true for high levels of TNF alpha and IL 6 in SF cell culture supernatant. CONCLUSION: The described changes in immunological parameters of humoral and cellular immunity are not specific for JCA. In the individual cases they can contribute to the diagnosis and monitoring of the disease. The investigation of sHLA molecules and cytokine profile should be restricted only for research. PMID- 11208503 TI - Repeated cyclosporine therapy of peripheral arthritis associated with ankylosing spondylitis. AB - BACKGROUND: A case history of a patient with ankylosing spondylitis and peripheral arthritis unresponsive to the conventional drug therapy, but successfully controlled by the use of cyclosporin. MATERIAL AND METHODS: In a 68 years old female patient with a 36 years history of typical ankylosing spondylitis a peripheral polyarthritis (hands, feet, wrists, and knees) developed. The patient did not suffer any other disease known to cause secondary spondylitis (psoriasis, inflammatory, bowel, disease). After the unsuccessful use of non-steroidal antiinflammatory drugs a combination therapy with cyclosporin (4 mg/kg/day) and azapropazone (300 mg t.i.d.) was introduced. RESULTS: Clinical improvement was achieved after 6 months of combined therapy, the polyarthritis completely resolved after one year. Therefore cyclosporin was discontinued. After one year the polyarthritis reappeared therefore the cyclosporin therapy was reinstituted with success. CONCLUSION: Cyclosporin has proved consistently effective in our case to control the peripheral arthritis associated with ankylosing spondylitis. PMID- 11208505 TI - Incidence of vesicoureteral reflux in siblings of children with reflux--our own observations. AB - BACKGROUND: The aim of the study was to evaluate the incidence of primary vesicoureteral reflux in siblings of children with reflux. MATERIAL AND METHODS: Ninety-four subjects aged 2-6, the siblings of children with reflux were examined. Our methods included: urinalysis, urine cultures, ultrasound examination of abdominal cavity in all the examined subjects. Voiding cystography was conducted in selected cases. RESULTS: Primary vesicoureteral reflux was found in the total of 10% of the siblings of children with reflux. The incidence of reflux was the highest in the youngest age group. CONCLUSIONS: The incidence of primary vesicoureteral reflux in the siblings of affected children being at least ten times higher than population risk supports the necessity of screening in this group. PMID- 11208504 TI - Positive and negative strands of HCV-RNA in sera and peripheral blood mononuclear cells of chronically hemodialyzed patients. AB - BACKGROUND: Hepatitis C virus (HCV) RNA can be detected in sera and peripheral blood mononuclear cells (PBMC) of patients undergoing chronic hemodialysis. However, the natural course of HCV infection in this group of patients is not fully known. Although the exact mechanism of HCV replication is not completely explained, there is evidence that HCV replicate through synthesis of complementary negative (-) RNA strand, whereas positive (+) RNA strand serves as a template. Thus, the detection of negative HCV-RNA strand can be regarded as a marker of ongoing viral replication. MATERIAL AND METHODS: We investigated the prevalence of (+) and (-) strands of HCV-RNAs in sera and PBMC of 45 chronically hemodialyzed patients using PCR methods. We also determined HCV genotypes and their subtypes by Inno-LIPA method. RESULTS: Eight (17.8%) of analyzed patients were anti-HCV positive. In this group, we detected HCV-RNA (+) strands in sera and PBMC in 2 and 4 cases respectively, whereas HCV-RNA (-) ones were found in PBMC of 4 patients. Among the remaining 37 anti-HCV negative patients we found HCV-RNA positive strands in sera and PBMC in 2 and 3 cases respectively, whereas HCV-RNA negative strand was present in PBMC in one of them. CONCLUSIONS: Our results indicate that HCV actively replicate in PBMC in chronically hemodialyzed patients. In number of patients HCV-RNAs can be detected only in PBMC without concomitant presence of viremia or anti-HCV in sera. We did not find any correlation between genotypes of HCV and presence of HCV-RNAs strands in PBMC of the patients. PMID- 11208506 TI - Skin prick test response to enzyme enolase of the baker's yeast (Saccharomyces cerevisiae) in diagnosis of respiratory allergy. AB - BACKGROUND: The aim of the study is to prove that Saccharomyces cerevisiae enolase, the major allergen of the baker's yeast, induces allergic immediate response in patients with inhalant allergy sensitized to Candida albicans extract. MATERIAL AND METHODS: The study was performed in three groups of patients: I. 20 atopic patients with respiratory allergy sensitized to Candida albicans and inhalant allergens (mite, feather, pollens) II. 30 patients with respiratory allergy, positive skin tests to inhalant allergens but negative skin tests to Candida albicans and other fungi; III. 20 nonatopic, healthy individuals. Skin prick test of purified enolase from Saccharomyces cerevisiae (bakers yeast) at concentration 1 and 10 mg/ml was performed in all groups. The results were documented planimetrically. RESULTS: 95% of patients sensitized to Candida albicans extract showed positive skin reactions to Saccharomyces cerevisiae enolase, 10% of patients of group II and none of the patients of the control group had positive skin responses to enolase. The mean wheal size (mm2) in skin prick test to Candida albicans, Saccharomyces cerevisiae enolase at concentration 10 mg/ml was x = 15.17 +/- 11.08, 15.76 +/- 19.67 and at concentration 1 mg/ml 10.02 +/- 10.49, respectively. CONCLUSIONS: 1. Saccharomyces cerevisiae enolase induces an immediate allergic reaction in skin in subjects with respiratory allergy and positive skin prick test results to Candida albicans and other fungi. 2. Enolase can be an important allergenic component of the Candida albicans extract. PMID- 11208507 TI - Results of IDA-FLAG programme in the treatment of recurrent acute myeloblastic leukaemia--preliminary report. AB - BACKGROUND: Unsatisfactory treatment results of acute myeloblastic leukaemia inspire the search for new drugs, characterised by higher efficiency and lower toxicity. The aim of the study was the assessment of the efficiency and side effects associated with the implementation of IDA-FLAG protocol. MATERIAL AND METHODS: The assessment of treatment results and undesirable effects was based on the material of 4 children with the relapse of acute myeloblastic leukaemia, after a total of 6 IDA-FLAG protocols. RESULTS: Complete remission was obtained in 2 (50%) children, with mean remission time of 13.5 months. One of the children underwent the transplantation of haematopoietic cells from unrelated donor. The main side effect observed was bone marrow aplasia. Leucopenia, granulocytopenia, thrombocytopenia and anaemia persisted for approx. 20 days. Apart from haematological symptoms, the following were also observed: the symptoms of intolerance after ARA-C, aspergillosis of paranasal sinuses and lungs and severe coagulation disorders. CONCLUSION: IDA-FLAG protocol may be recommended for use in children with AML relapse and the undesirable effects observed are acceptable. PMID- 11208508 TI - Population data for the STR systems D8S1132, CD4, VWA and TH01 in the region of Podlasie (northeastern Poland). AB - BACKGROUND: STR systems are widely used in forensic casework due to their discriminating power and high sensitivity. The aim of the study was to determine allele frequencies and forensic efficiency parameters of the STRs D8S1132, CD4, VWA and TH01 in a population sample of Podlasie (Northeastern Poland). MATERIAL AND METHODS: Blood specimens were collected from the unrelated individuals in Podlasie, Poland. The DNA samples were extracted with Chelex method and amplified by PCR technique. The PCR products were analyzed by the PAG horizontal electrophoresis with discontinuous buffer system and then silver stained. RESULTS: All common alleles included in the allelic ladders were found. For all loci examined no deviations from Hardy-Weinberg equilibrium were found. CONCLUSION: The TH01, VWA and D8S1132 systems have been confirmed as particularly useful in the paternity testing and the individualization of biological evidence. PMID- 11208509 TI - Endogenous lipoid pneumonia associated with undifferentiated connective tissue disease (UCTD). AB - BACKGROUND: Lipoid pneumonia is a rare pulmonary disease, a form of pneumonia that has no classical radiological appearance, thus it can imitate other lung diseases. Lipoid pneumonia is usually classified into two major groups, depending on whether the source of oil/fat in the respiratory tract is from an exogenous or endogenous source. Undifferentiated connective tissue disease is a term used by rheumatologists to define a group of diffuse connective tissue disorders that lack definitive characteristics of any particular well-defined disorder. MATERIAL AND METHODS: A case study is reported of concomitant undifferentiated connective tissue disease and endogenous lipoid pneumonia. RESULTS: Histologically the macrophages appeared filled with lipid and were similar to atherosclerotic foam cell macrophages. Antibiotic and antimycotic treatments were ineffective. However, with concomitant steroid treatment, the patient exhibited absence of lung infiltration as well as other symptoms and was discharged. Therefore it is concluded that the lipoid pneumonia was steroid dependent. CONCLUSION: Since the patient's condition responded to steroid treatment, and it is clear that steroids inhibit phospholipase activity, the authors speculate that the subsequent decreased endoperoxide production may diminish lipid uptake by macrophages via decreasing modification of LDL or other lipid sources. PMID- 11208511 TI - Diabetic ketoacidosis in a patient with acromegaly. AB - Abnormalities of glucose metabolism are a common feature of acromegaly. Overt diabetes mellitus develops in about 10-15% of patients. We present an unusual complication of acromegaly: a 37-year old man with a 2-year history of acromegaly developed diabetic ketoacidosis 3 weeks after transsphenoidal adenomectomy. No specific cause for this sudden metabolic derangement could be demonstrated. Insulin need was very high in the first days after the onset of ketoacidosis, but was considerably reduced after initiation of treatment with octreotide and after successful re-operation. PMID- 11208510 TI - Clinical onset of the Crohn's disease after eradication therapy of Helicobacter pylori infection. Does Helicobacter pylori infection interact with natural history of inflammatory bowel diseases? AB - BACKGROUND: There are conflicting reports concerning the prevalence of Helicobacter pylori infection in patients with inflammatory bowel diseases: some studies connected Sulphasalazine therapy and lower incidence of Helicobacter pylori infection, but others showed lower prevalence of Helicobacter pylori infection in inflammatory bowel diseases despite the choice of therapy. CASE REPORT: A 28-year-old male patient presented in January 1996 with the symptoms of ulcer like dyspepsia. There was no significant abnormality on physical examination, laboratory testing and abdominal ultrasound. Histology examination of the biopsy specimen taken during the upper endoscopy revealed Helicobacter pylori associated active gastritis only in the corporal part of the stomach. After two weeks eradication therapy (Omeprazole, Amoxicillin) he was well. Three months later, at the control endoscopy, granulomatous gastritis of the corporal localization was detected, without Helicobacter pylori present. Antral mucosa appeared normal, both, on endoscopy and histology examination. In July 1996 he started with cramping abdominal pain, mild periodical fever and episodes of watery diarrhea. In laboratory results we found nonspecific signs of inflammation. We repeated upper endoscopy, colonoscopy and enteroclysis--with evidence of segmental stenotic lesions of the upper part of ileum and jejunum. Again, we confirmed granulomatous gastritis and small granuloma in the proximal jejunum. After starting the 5-ASA therapy in combination with Metronidazol, patient was better clinical condition, and laboratory results were normal. We suggested mesalamine maintenance therapy 1 gr. every day, and three years later he is well, in clinical remission of Crohn's disease. CONCLUSION: The clinical course of the Crohn's disease maybe "sui generis" connected with Helicobacter pylori infection- but the exact mechanisms remain to be discovered. PMID- 11208512 TI - In vitro evaluation of the embolic risk of diagnostic and therapeutic intravascular procedures. AB - BACKGROUND: The purpose of the study was to evaluate the risk of distal embolisation in a silicon model during different endovascular diagnostic and therapeutic procedures. MATERIAL AND METHODS: Endovascular technics, such as guidewire and catheter advancement, metal stent placement and balloon angioplasty were compared. Clots were produced from human blood sample. The transparent silicon model was filled with saline, flow was generated by an hydraulic pump. Stenosis was created by mechanical compression. The size of the circulating particles were measured with a mesh of nylon filters. RESULTS: No loose particles were detected using guidewire, pigtail and straight catheters. Balloon inflation induced embolisation of particles ranging from 100 microns to 10 mm in length. Deployment of self expandable metallic stents did not result in particle migration but secondary angioplasty inside the stent detached particles (ranging from 400 microns to 12 mm in length). Deployment of balloon expandable stent yielded in the stretching of the clot, which became sometimes longer than the stent, resulting in the detachment of the non covered portion. CONCLUSION: The risk of distal embolisation during guide-wires and catheters manipulation is not significant. Balloon catheters and secondary angioplasty after deployment of self expanding stents caused large particles detachment. PMID- 11208513 TI - Towards MRI guided surgical manipulator. AB - BACKGROUND: The advantages of surgical robots and manipulators are well recognized in the clinical and technical community. Precision, accuracy and the potential for telesurgery are the prime motivations in applying advanced robot technology in surgery. In this paper critical interactions between Magnetic Resonance Imaging equipment and mechatronic devices are discussed and a novel Magnetic Resonance compatible surgical robot is described. MATERIAL AND METHODS: Experimental results of the effects from several passive (metallic materials) and active (ultrasound motors) mechanical elements are demonstrated. The design principles for Magnetic Resonance compatible robots are established and the compatibility of the proposed robot is assessed by comparing images taken with and without the robot's presence within Signa SP/I GE Medical Systems scanner. RESULTS: The results showed that, in principle, it is possible to construct precision mechatronic devices intended to operate inside MR scanner. Use of such a device will not cause image shift or significant degradation of signal-to-noise ratio. An MR compatible surgical assist robot was designed and constructed. The robot is not affected by the presence of strong magnetic fields and is able to manoeuvre during imaging without compromising the quality of images. A novel image-guided robot control scheme was proposed. As a part of the control scheme, biomechanics-based organ deformation model was constructed and validated by in vivo experiment. It has been recognised that for robust control of an image guided surgical robot the precise knowledge of the mechanical properties of soft organs operated on must be known. As an illustration, results in mathematical modelling and computer simulation of brain deformation are given. CONCLUSION: The novel MR compatible robot was designed to position and direct an axisymmetric tool, such as a laser pointer or a biopsy catheter. New Robot control system based on the prediction of soft organ deformation was proposed. PMID- 11208514 TI - Bladder cancer--genetic overview. AB - BACKGROUND: This article review the serial genetic changes which are responsible to the initiation and progression of bladder cancer. Knowledge of the exact genetic alteration has a direct implication on the development of knew more sensitive and specific tool for an early diagnosis and better prognosis calculations. CONCLUSION: Bladder cancer develop and progress through a series of genetic alterations. Understanding of the genetic mechanisms which lead to malignant transformation gave rise to the development of various genetic mechanisms which lead to malignant transformation gave rise to the development of various genetic tools providing better ability of early detection and more accurate prognosis prediction. PMID- 11208515 TI - Insulin receptor--structural and functional characteristics. AB - The insulin receptor is a complex multifunctional protein located on the cell surface within the fluid mosaic matrix of the plasma membrane. Its ability to bind insulin is determined by structural and spatial specificity, high affinity and reversibility. Insulin action at the cellular level can be considered in three stages. The first stage includes the insulin receptor itself, the insulin substrate (IRS-1) and the molecules that interact with IRS-1. The second stage is that of cascade phosphorylation and dephosphorylation. The third stage concerns the final biological effects of the insulin cascade. The biological specificity of insulin binding and heterogeneity of insulin action in different cells has been well documented. This review intends to summarize the available data of structural and functional characteristics of insulin receptor. PMID- 11208516 TI - Focus on "Essential role for IL-6 in postresuscitation inflammation in hemorrhagic shock". PMID- 11208517 TI - Fiber type-specific expression of major proteolytic systems in fast- to slow transforming rabbit muscle. AB - The present study investigates the role of two major proteolytic systems in transforming rabbit and rat muscles. The fast-to-slow transformation of rabbit muscle by chronic low-frequency stimulation (CLFS) induces fast-to-slow transitions of intact, mature fibers and replacement of degenerating fibers by newly formed slow fibers. Ubiquitination, an indicator of the ATP-dependent proteasome system, and calpain activity were measured in homogenates of control and stimulated extensor digitorum longus muscles. Calpain activity increased similarly (approximately 2-fold) in stimulated rat and rabbit muscles. CLFS had no effect on protein ubiquitination in rat muscle but led to elevations in ubiquitin protein conjugates in rabbit muscle. Immunohistochemistry was used to study the distribution of micro-calpain and m-calpain and of ubiquitinated proteins in myosin heavy chain-based fiber types. The findings suggest that both proteolytic systems are involved in fiber transformation and replacement. Transforming mature fibers displayed increases in micro-calpain and accumulation of ubiquitin protein conjugates. The majority of these fibers were identified as type IIA. Enhanced ubiquitination was also observed in degenerating and necrotic fibers. Such fibers additionally displayed elevated m-calpain levels. Conversely, p94, the skeletal muscle-specific calpain, decayed rapidly after stimulation onset and was hardly detectable after 4 days of CLFS. PMID- 11208518 TI - Hypertonicity-induced phosphorylation and nuclear localization of the transcription factor TonEBP. AB - The accumulation of compatible osmolytes during osmotic stress is observed in virtually all organisms. In mammals, the hypertonicity-induced expression of osmolyte transporters and synthetic enzymes is conferred by the presence of upstream tonicity-responsive enhancer (TonE) sequences. Recently, we described the cloning and initial characterization of TonE-binding protein (TonEBP), a transcription factor that translocates to the nucleus and associates with TonE sequences in a tonicity-dependent manner. We now report that hypertonicity induces an increase in TonEBP phosphorylation that temporally correlates with increased nuclear localization of the molecule. TonEBP phosphorylation is not affected by a number of kinase inhibitors, including the p38 inhibitor SB-203580. In addition, in vitro binding assays show that the association of TonEBP with TonE sequences is not affected by phosphorylation. Thus TonEBP phosphorylation is an early step in the response of cells to hypertonicity and may be required for nuclear import or retention. PMID- 11208519 TI - Regional variation in myosin isoforms and phosphorylation at the resting tone in urinary bladder smooth muscle. AB - Urinary bladder filling and emptying requires coordinated control of bladder body and urethral smooth muscles. Bladder dome, midbladder, base, and urethra showed significant differences in the percentage of 20-kDa myosin light chain (LC20) phosphorylation (35.45 +/- 4.6, 24.7 +/- 2.2, 13.6+/- 2.1, and 12.8 +/- 2.7%, respectively) in resting muscle. Agonist-mediated force was associated with a rise in LC20 phosphorylation, but the extent of phosphorylation at all levels of force was less for urethral than for bladder body smooth muscle. RT-PCR and quantitative competitive RT-PCR analyses of total RNA from bladder body and urethral smooth muscles revealed only a slight difference in myosin heavy chain mRNA copy number per total RNA, whereas mRNA copy numbers for NH2-terminal isoforms SM-B (inserted) and SM-A (noninserted) in these muscles showed a significant difference (2.28 x 10(8) vs. 1.68 x 10(8) for SM-B and 0.12 x 10(8) vs. 0.42 x 10(8) for SM-A, respectively), which was also evident at the protein level. The ratio of COOH-terminal isoforms SM2:SM1 in the urethra was moderately but significantly lower than that in other regions of the bladder body. A high degree of LC20 phosphorylation and SM-B in the bladder body may help to facilitate fast cross-bridge cycling and force generation required for rapid emptying, whereas a lower level of LC20 phosphorylation and the presence of a higher amount of SM-A in urethral smooth muscle may help to maintain the high basal tone of urethra, required for urinary continence. PMID- 11208520 TI - alpha1H T-type Ca2+ channel is the predominant subtype expressed in bovine and rat zona glomerulosa. AB - The low voltage-activated (T-type) Ca2+ channel has been implicated in the regulation of aldosterone secretion from the adrenal zona glomerulosa by extracellular K+ levels, angiotensin II, and ACTH. However, the identity of the specific subtype mediating this regulation has not been determined. We utilized in situ hybridization to examine the distribution of three newly cloned members of the T-type Ca2+ channel family, alpha1G, alpha1H, and alpha1I, in the rat and bovine adrenal gland. Substantial expression of only the mRNA transcript for the alpha1H-subunit was detected in the zona glomerulosa of both rat and bovine. A much weaker expression signal was detected for the alpha1H transcript in the zona fasciculata of bovine. Whole cell recordings of isolated bovine adrenal zona glomerulosa cells showed the native low voltage-activated current to be inhibited by NiCl2 with an IC50 of 6.4 +/- 0.2 microM. Because the alpha1H subtype exhibits similar NiCl2 sensitivity, we propose that the alpha1H subtype is the predominant T-type Ca2+ channel present in the adrenal zona glomerulosa. PMID- 11208521 TI - Muscle LIM protein is upregulated in fast skeletal muscle during transition toward slower phenotypes. AB - Muscle LIM protein (MLP) is constitutively expressed in slow, but undetectable in fast, muscles of the rat. Here we show that MLP was upregulated at both the mRNA and protein levels under experimental conditions leading to transitions from fast to slower phenotypes. Chronic low-frequency stimulation and mechanical overloading by synergist removal both induced fast-to-slow shifts in myosin heavy chain (MHC) isoforms and expression of MLP in fast muscles. High amounts of MLP mRNA and protein were also present in fast muscles of the myotonic, hyperactive ADR mouse. Hypothyroidism evoked shifts in myosin composition toward slower isoforms and increased the MLP protein content of soleus (SOL) muscle but failed to induce MLP in fast muscles. Unweighting by hindlimb suspension elicited slow to-fast transitions in MHC expression without altering MLP levels in SOL muscle. Hyperthyroidism shifted the MHC pattern toward faster isoforms but did not affect MLP content in SOL muscle. We conclude that alterations in MLP expression are associated with transitions from fast to slower phenotypes but not with slow-to fast muscle fiber transitions. PMID- 11208522 TI - Effect of culture PO2 on macrophage (RAW 264.7) nitric oxide production. AB - Macrophages are commonly cultured at a PO2 of 149 Torr, but tissue macrophages in vivo live in an environment of much lower oxygen tension. Despite the many potential mechanisms for changes in oxygen tension to influence nitric oxide (NO) synthesis, there have been few reports investigating the effect of PO2 on macrophage NO production. With the use of a culture chamber designed to rigorously control oxygen tension, we investigated the effects of culture PO2 on macrophage NO production, inducible nitric oxide synthase (iNOS) activity, iNOS protein, and tumor necrosis factor production. NO production and iNOS activity were linearly related in the range of 39.4 to 677 Torr, but not in the range of 1.03 to 39.4 Torr. Therefore, results obtained in vitro for the high oxygen tensions commonly used in cell culture were quantitatively and qualitatively different from results obtained in cells cultured at the lower oxygen tensions that more accurately reflect the in vivo environment. The influence of oxygen tension on NO production has implications for cell culture methodology and for the relationship between microcirculatory dysfunction and inflammatory responses in rodent models of sepsis. PMID- 11208523 TI - Excitability and contractility of skeletal muscle engineered from primary cultures and cell lines. AB - The purpose of this study was to compare the excitability and contractility of three-dimensional skeletal muscle constructs, termed myooids, engineered from C2C12 myoblast and 10T1/2 fibroblast cell lines, primary muscle cultures from adult C3H mice, and neonatal and adult Sprague-Dawley rats. Myooids were 12 mm long, with diameters of 0.1-1 mm, were excitable by transverse electrical stimulation, and contracted to produce force. After approximately 30 days in culture, myooid cross-sectional area, rheobase, chronaxie, resting baseline force, twitch force, time to peak tension, one-half relaxation time, and peak isometric force were measured. Specific force was calculated by dividing peak isometric force by cross-sectional area. The specific force generated by the myooids was 2-8% of that generated by skeletal muscles of control adult rodents. Myooids engineered from C2C12-10T1/2 cells exhibited greater rheobase, time to peak tension, and one-half relaxation time than myooids engineered from adult rodent cultures, and myooids from C2C12-10T1/2 and neonatal rat cells had greater resting baseline forces than myooids from adult rodent cultures. PMID- 11208524 TI - Cryptdin-3 induces novel apical conductance(s) in Cl- secretory, including cystic fibrosis, epithelia. AB - Opening of anion-conductive pathways in apical membranes of secretory cells lining mucosal surfaces is a critical step in salt and water secretion and, thus, hydration of sites including airway and intestine. In intestine, Paneth cells are positioned at the base of the secretory gland (crypt) and release defensin peptide, in mice termed cryptdins, into the crypt lumen. Because at least some defensins have been shown to form anion-conductive channels in phospholipid bilayers, we tested whether these endogenous antimicrobial peptides could act as soluble inducers of channel-like activity when applied to apical membranes. To directly evaluate the possibility of cryptdin-3-mediated apical anion conductance (G(ap)), we have utilized amphotericin B to selectively permeabilize basolateral membranes of electrically tight monolayers of polarized human intestinal secretory epithelia (T84 cells), thus isolating the apical membrane for study. Cryptdin-3 induces G(ap) that is voltage independent (deltaG(ap) = 1.90 +/- 0.60 mS/cm2) and exhibits ion selectivity contrasting to that elicited by forskolin or thapsigargin (for cryptdin-3, Cl- = gluconate; for forskolin and thapsigargin, Cl >> gluconate). We cannot exclude the possibility that the macroscopic current induced by cryptdin could be the sum of cation and Cl- currents. Cryptdin-3 induces a current in basolaterally permeabilized epithelial monolayers derived from airway cells harboring the deltaF508 mutation of cystic fibrosis (CF; deltaG(ap) = 0.80 +/- 0.06 mS/cm2), demonstrating that cryptdin-3 restores anion secretion in CF cells; this occurs independently of the CF transmembrane conductance regulator channel. These results support the idea that cryptdin-3 may associate with apical membranes of Cl--secreting epithelia and self-assemble into conducting channels capable of mediating a physiological response. PMID- 11208525 TI - State-dependent modification of ATP-sensitive K+ channels by phosphatidylinositol 4,5-bisphosphate. AB - With inside-out patch recordings in ventricular myocytes from the hearts of guinea pigs, we studied ATP-sensitive K+ (K(ATP)) channels activated by phosphatidylinositol 4,5-bisphosphate (PIP2) with respect to sensitivity to ATP when in either a rundown state (RS) or a non-rundown state (NRS). Rundown of K(ATP) channels was induced by exposure either to ATP-free solution or to ATP free solution containing 19 microM Ca2+. Exposure of membrane patches to 10 microM PIP2 reactivated channels with both types of rundown. The reactivation by PIP2 did not require ATP in the bath. The IC50 of channels recovered from RS and before the rundown was 37.1 and 31.1 microM, respectively. PIP2 irreversibly increased the mean current when the channel was in the NRS. This was associated with a shift of IC50 to 250.6 microM after PIP2 exposure. PIP2 activates NRS K(ATP) channels by decreasing their sensitivity to ATP, whereas PIP2 reactivates RS-K(ATP) channels independently of ATP without changing ATP sensitivity. PMID- 11208526 TI - Single rabbit stomach smooth muscle cell myosin heavy chain SMB expression and shortening velocity. AB - Isolated single smooth muscle cells (SMCs) from different regions of the rabbit stomach were used to determine a possible correlation between unloaded shortening velocity and smooth muscle (SM) myosin heavy chain (MHC) S1 head isoform composition (SMA, no head insert; SMB, with head insert). alpha-Toxin permeabilized isolated single cells were maximally activated to measure unloaded shortening velocity and subsequently used in an RT-PCR reaction to determine the SMA/SMB content of the same cell. SM MHC SMA and SMB isoforms are uniquely distributed in the stomach with cells from the fundic region expressing little SMB (38.1 +/- 7.3% SMB; n = 16); cells from the antrum express primarily SMB (94.9 +/- 1.0% SMB; n = 16). Mean fundic cell unloaded shortening velocity was 0.014 +/- 0.002 cell lengths/s compared with 0.036 +/- 0.002 for the antrum cells. Unloaded shortening velocity in these cells was significantly correlated with their percent SMB expression (r2 = 0.58). Resting cell length does not correlate with the percent SMB expression (n = 32 cells). Previously published assays of purified or expressed SMA and SMB heavy meromyosin show a twofold difference in actin filament sliding speed in in vitro motility assays. Extrapolation of our data to 0-100% SMB would give a 10-fold range of shortening velocity, which is closer to the approximately 20-fold range reported from various SM tissues. This suggests that mechanisms in addition to the MHC S1 head isoforms regulate shortening velocity. PMID- 11208527 TI - Polyamines in pancreatic islets of obese-hyperglycemic (ob/ob) mice of different ages. AB - To further evaluate the role of polyamines in insulin production and cell replication in diabetic pancreatic islets, we have studied hyperplastic islets of obese-hyperglycemic mice of different ages and normal islets of the same strain. The aims of the study were to investigate the impact of the diabetic state and aging on polyamine contents and requirements in these islets. Cultured islets from lean and obese animals contained significantly less polyamines than freshly isolated islets. Spermine-to-spermidine ratio was elevated in freshly isolated islets from young obese mice compared with those from lean mice. In islets from old obese animals, spermidine content was decreased, whereas the content of spermine was not different from that of young obese mice. The physiological significance of polyamines was investigated by exposing islets in tissue culture to inhibitors of polyamine synthesis. This treatment caused a partial polyamine depletion in whole islets but failed to affect polyamine content of cell nuclei. Insulin content was not affected in polyamine-deficient islets of obese mice, irrespective of age, in contrast to decreased islet insulin content in polyamine depleted young lean animals. Polyamine depletion depressed DNA synthesis rate in obese mouse islets; in lean mice it actually stimulated DNA synthesis. We concluded that important qualitative and quantitative differences exist between islets from obese-hyperglycemic and normal mice with respect to polyamine content and requirements of polyamines for regulation of insulin content and cell proliferation. The results suggest that spermine may be involved in mediating the rapid islet cell proliferation noted early in obese-hyperglycemic syndrome, but changes in spermine concentration do not seem to account for the decline in islet cell DNA synthesis in aged normoglycemic animals. PMID- 11208528 TI - Troponin I chimera analysis of the cardiac myofilament tension response to protein kinase A. AB - Viral-mediated gene transfer of troponin I (TnI) isoforms and chimeras into adult rat cardiac myocytes was used to investigate the role TnI domains play in the myofilament tension response to protein kinase A (PKA). In myocytes expressing endogenous cardiac TnI (cTnI), PKA phosphorylated TnI and myosin-binding protein C and decreased the Ca2+ sensitivity of myofilament tension. In marked contrast, PKA did not influence Ca2+-activated tension in myocytes expressing the slow skeletal isoform of TnI or a chimera (N-slow/card-C TnI), which lack the unique phosphorylatable amino terminal extension found in cTnI. PKA-mediated phosphorylation of a second TnI chimera, N-card/slow-C TnI, which has the amino terminal region of cTnI, caused a decrease in the Ca2+ sensitivity of tension comparable in magnitude to control myocytes. Based on these results, we propose the amino terminal region shared by cTnI and N-card/slow-C TnI plays a central role in determining the magnitude of the PKA-mediated shift in myofilament Ca2+ sensitivity, independent of the isoform-specific functional domains previously defined within the carboxyl terminal backbone of TnI. Interestingly, exposure of permeabilized myocytes to acidic pH after PKA-mediated phosphorylation of cTnI resulted in an additive decrease in myofilament Ca2+ sensitivity. The isoform specific, pH-sensitive region within TnI lies in the carboxyl terminus of TnI, and the additive response provides further evidence for the presence of a separate domain that directly transduces the PKA phosphorylation signal. PMID- 11208529 TI - Regulatory pathways and uptake of L-DOPA by capillary cerebral endothelial cells, astrocytes, and neuronal cells. AB - We examined the nature and regulation of the inward L-3,4-dihydroxyphenylalanine (L-DOPA) transporter in rat capillary cerebral endothelial (RBE4) cells, type 1 astrocytes (DI TNC1), and Neuro-2a neuroblastoma cells. In all three cell types, the inward transfer of L-DOPA was largely promoted through the 2-aminobicyclo (2,2,1)-heptane-2-carboxylic acid-sensitive and sodium-independent L-type amino acid transporter. Only in DI TNC1 cells was the effect of maneuvers that increase intracellular cAMP levels accompanied by increases in L-DOPA uptake. Also, only in DI TNC1 cells was the effect of the guanylyl cyclase inhibitor LY-83583 accompanied by a 65% increase in L-DOPA accumulation, whereas the nitric oxide donor sodium nitroprusside produced a 25% decrease in L-DOPA accumulation. In all three cell types, the Ca2+/calmodulin inhibitors calmidazolium and trifluoperazine inhibited L-DOPA uptake in a noncompetitive manner. Thapsigargin (1 and 3 microM) and A-23187 (1 and 3 microM) failed to alter L-DOPA accumulation in RBE4 and Neuro-2a cells but markedly increased L-DOPA uptake in DI TNC1 cells. We concluded that L-DOPA in RBE4, DI TNC1, and Neuro-2a cells is transported through the L-type amino acid transporter and appears to be under the control of Ca2+/calmodulin-mediated pathways. Astrocytes, however, are endowed with other processes that appear to regulate the accumulation of L-DOPA, responding positively to increases in intracellular Ca2+ and cAMP and to decreases in cGMP. PMID- 11208530 TI - Essential role for IL-6 in postresuscitation inflammation in hemorrhagic shock. AB - Interleukin-6 (IL-6) is produced within multiple tissues and can be readily detected in the circulation in resuscitated hemorrhagic shock (HS). Instillation of IL-6 into lungs of normal rats induces polymorphonuclear neutrophilic granulocyte (PMN) infiltration and lung damage, while infusion of IL-6 into the systemic circulation of rats during resuscitation from HS reduces PMN recruitment and lung injury. The current study was designed to determine whether or not IL-6 makes an essential contribution to postresuscitation inflammation and which of the two effects of IL-6, its local proinflammatory effect or its systemic anti inflammatory effect, is dominant in HS. Wild-type and IL-6-deficient mice were subjected to HS followed by resuscitation and death 4 h later. IL-6-deficient mice subjected to HS did not demonstrate any features of postresuscitation inflammation observed in wild-type mice, including increased PMN infiltration into the lungs, increased alveolar cross-sectional surface area, increased PMN infiltration into the liver, increased liver necrosis, increased signal transducer and activator of transcription 3 activation, and increased nuclear factor-kappaB activity. These findings indicate that IL-6 is an essential component of the postresuscitation inflammatory cascade in HS and that the local proinflammatory effects of IL-6 on PMN infiltration and organ damage in HS dominate over the anti-inflammatory effects of systemic IL-6. PMID- 11208531 TI - Static stretch increases c-Jun NH2-terminal kinase activity and p38 phosphorylation in rat skeletal muscle. AB - Physical exercise and contraction increase c-Jun NH2-terminal kinase (JNK) activity in rat and human skeletal muscle, and eccentric contractions activate JNK to a greater extent than concentric contractions in human skeletal muscle. Because eccentric contractions include a lengthening or stretch component, we compared the effects of isometric contraction and static stretch on JNK and p38, the stress-activated protein kinases. Soleus and extensor digitorum longus (EDL) muscles dissected from 50- to 90-g male Sprague-Dawley rats were subjected to 10 min of electrical stimulation that produced contractions and/or to 10 min of stretch (0.24 N tension, 20-25% increase in length) in vitro. In the soleus muscle, contraction resulted in a small, but significant, increase in JNK activity (1.8-fold above basal) and p38 phosphorylation (4-fold). Static stretch had a much more profound effect on the stress-activated protein kinases, increasing JNK activity 19-fold and p38 phosphorylation 21-fold. Increases in JNK activation and p38 phosphorylation in response to static stretch were fiber-type dependent, with greater increases occurring in the soleus than in the EDL. Immunohistochemistry performed with a phosphospecific antibody revealed that activation of JNK occurred within the muscle fibers. These studies suggest that the stretch component of a muscle contraction may be a major contributor to the increases in JNK activity and p38 phosphorylation observed after exercise in vivo. PMID- 11208532 TI - Differential expression of KvLQT1 and its regulator IsK in mouse epithelia. AB - KCNQ1 is the human gene responsible in most cases for the long QT syndrome, a genetic disorder characterized by anomalies in cardiac repolarization leading to arrhythmias and sudden death. KCNQ1 encodes a pore-forming K+ channel subunit termed KvLQT1 which, in association with its regulatory beta-subunit IsK (also called minK), produces the slow component of the delayed-rectifier cardiac K+ current. We used in situ hybridization to localize KvLQT1 and IsK mRNAs in various tissues from adult mice. We showed that KvLQT1 mRNA expression is widely distributed in epithelial tissues, in the absence (small intestine, lung, liver, thymus) or presence (kidney, stomach, exocrine pancreas) of its regulator IsK. In the kidney and the stomach, however, the expression patterns of KvLQT1 and IsK do not coincide. In many tissues, in situ data obtained with the IsK probe coincide with beta-galactosidase expression in IsK-deficient mice in which the bacterial lacZ gene has been substituted for the IsK coding region. Because expression of KvLQT1 in the presence or absence of its regulator generates a K+ current with different biophysical characteristics, the role of KvLQT1 in epithelial cells may vary depending on the expression of its regulator IsK. The high level of KvLQT1 expression in epithelial tissues is consistent with its potential role in K+ secretion and recycling, in maintaining the resting potential, and in regulating Cl- secretion and/or Na+ absorption. PMID- 11208533 TI - Tissue distribution and subcellular localization of the ClC-5 chloride channel in rat intestinal cells. AB - ClC-5 is the Cl- channel that is mutated in Dent's disease, an X-chromosome linked disease characterized by low molecular weight proteinuria, hypercalciuria, and kidney stones. It is predominantly expressed in endocytically active renal proximal cells. We investigated whether this Cl- channel could also be expressed in intestinal tissues that have endocytotic machinery. ClC-5 mRNA was detected in the rat duodenum, jejunum, ileum, and colon. Western blot analyses revealed the presence of the 83-kDa ClC-5 protein in these tissues. Indirect immunofluorescence studies showed that ClC-5 was mainly concentrated in the cytoplasm above the nuclei of enterocytes and colon cells. ClC-5 partially colocalized with the transcytosed polymeric immunoglobulin receptor but was not detectable together with the brush-border-anchored sucrase isomaltase. A subfractionation of vesicles obtained by differential centrifugation showed that ClC-5 is associated with the vacuolar 70-kDa H+-ATPase and the small GTPases rab4 and rab5a, two markers of early endosomes. Thus these results indicate that ClC-5 is present in the small intestine and colon of rats and suggest that it plays a role in the endocytotic pathways of intestinal cells. PMID- 11208534 TI - Expression of extracellular calcium-sensing receptor in human osteoblastic MG-63 cell line. AB - We have previously shown the expression of the extracellular calcium (Ca2+o) sensing receptor (CaR) in osteoblast-like cell lines, and others have documented its expression in sections of murine, bovine, and rat bone. The existence of the CaR in osteoblasts remains controversial, however, since some studies have failed to document its expression in the same osteoblast-like cell lines. The goals of the present study were twofold. 1) We sought to determine whether the CaR is expressed in the human osteoblast-like cell line, MG-63, which has recently been reported by others not to express this receptor. 2) We investigated whether the CaR, if present in MG-63 cells, is functionally active, since most previous studies have not proven the role of the CaR in mediating known actions of Ca2+o on osteoblast-like cells. We used immunocytochemistry and Western blotting with the specific, affinity-purified anti-CaR antiserum 4637 as well as Northern blot analysis and RT-PCR using a riboprobe and PCR primers specific for the human CaR, respectively, to show readily detectable CaR protein and mRNA expression in MG-63 cells. Finally, we employed the patch-clamp technique to show that an elevation in Ca2+o as well as the specific, allosteric CaR activator NPS R-467 (0.5 microM), but not its less active stereoisomer NPS S-467 (0.5 microM), activate an outward K+ channel in MG-63 cells, strongly suggesting that the CaR in MG-63 cells is not only expressed but is functionally active. PMID- 11208535 TI - Model organisms: new insights into ion channel and transporter function. L-type calcium channels regulate epithelial fluid transport in Drosophila melanogaster. AB - The neuropeptide CAP2b stimulates fluid transport obligatorily via calcium entry, nitric oxide, and cGMP in Drosophila melanogaster Malpighian (renal) tubules. We have shown by RT-PCR that the Drosophila L-type calcium channel alpha1-subunit genes Dmca1D and Dmca1A (nbA) are both expressed in tubules. CAP2b-stimulated fluid transport and cytosolic calcium concentration ([Ca2+]i) increases are inhibited by the L-type calcium channel blockers verapamil and nifedipine. cGMP stimulated fluid transport is verapamil and nifedipine sensitive. Furthermore, cGMP induces a slow [Ca2+]i increase in tubule principal cells via verapamil- and nifedipine-sensitive calcium entry; RT-PCR shows that tubules express Drosophila cyclic nucleotide-gated channel (cng). Additionally, thapsigargin-induced [Ca2+]i increase is verapamil sensitive. Phenylalkylamines bind with differing affinities to the basolateral and apical surfaces of principal cells in the main segment; however, dihydropyridine binds apically in the tubule initial segment. Immunocytochemical evidence suggests localization of alpha1-subunits to both basolateral and apical surfaces of principal cells in the tubule main segment. We suggest roles for L-type calcium channels and cGMP-mediated calcium influx in both calcium signaling and fluid transport mechanisms in Drosophila. PMID- 11208536 TI - bHLH transcription factor MyoD affects myosin heavy chain expression pattern in a muscle-specific fashion. AB - A strong correlative pattern between MyoD gene expression and myosin heavy chain IIB (MHC IIB) gene expression exists. To test whether this correlative relationship is causative, MHC gene expression in muscles from MyoD(-/-) mice was analyzed. The MHC IIB gene was not detectable in the MyoD(-/-) diaphragm, whereas the MHC IIB protein made up 10.0 +/- 1.7% of the MHC protein pool in the wild type (WT) mouse diaphragm. Furthermore, the MHC IIA protein was not detectable in the MyoD(-/-) biceps brachii, and the MHC IIB protein was overexpressed in the masseter. To examine whether MyoD is required for the upregulation of the MHC IIB gene within slow muscle after disuse, MyoD(-/-) and WT hindlimb musculature was unweighted. MyoD(-/-) exhibited a diminished response in the upregulation of the MHC IIB mRNA within the soleus muscle as a result of the hindlimb unweighting. Collectively, these data suggest that MyoD plays a role in the MHC profile in a muscle-specific fashion. PMID- 11208537 TI - Stress and the gastrointestinal tract III. Stress-related alterations of gut motor function: role of brain corticotropin-releasing factor receptors. AB - Alterations of gastrointestinal (GI) motor function are part of the visceral responses to stress. Inhibition of gastric emptying and stimulation of colonic motor function are the commonly encountered patterns induced by various stressors. Activation of brain corticotropin-releasing factor (CRF) receptors mediates stress-related inhibition of upper GI and stimulation of lower GI motor function through interaction with different CRF receptor subtypes. CRF subtype 1 receptors are involved in the colonic and anxiogenic responses to stress and may have clinical relevance in the comorbidity of anxiety/depression and irritable bowel syndrome. PMID- 11208538 TI - Microbes and microbial toxins: paradigms for microbial-mucosal interactions II. The integrated response of the intestine to Clostridium difficile toxins. AB - Clostridium difficile, the major etiologic factor of antibiotic-associated diarrhea and colitis, mediates its effects by releasing two large protein exotoxins, toxins A and B. A major toxin effect is related to the disassembly of actin microfilaments, leading to impairment of tight junctions in human colonocytes. The mechanism of actin disaggregation involves monoglucosylation of the signaling proteins Rho A, Rac, and Cdc 42, which control stress fiber formation directly by toxins A and B. An important aspect of C. difficile infection is the acute necroinflammatory changes seen in patients with pseudomembranous colitis. The early mechanism of toxin-mediated inflammation involves toxin effects on cellular mitochondria, release of reactive oxygen species, and activation of mitogen-activated protein kinases and the transcription factor nuclear factor-kappaB. Injection of toxin A into animal intestine triggers secretion of fluid and intestinal inflammation characterized by epithelial cell destruction and neutrophil activation. A critical feature of C. difficile enterotoxicity is communication between enterocytes and lamina propria nerves, macrophages, and mast cells mediated via release of neuropeptides and proinflammatory cytokines. PMID- 11208539 TI - Role of promoter methylation in increased methionine adenosyltransferase 2A expression in human liver cancer. AB - Methionine adenosyltransferase (MAT), an essential enzyme that catalyzes the formation of S-adenosylmethionine (SAM), is encoded by two genes, MAT1A (liver specific) and MAT2A (non-liver-specific). We showed a switch from MAT1A to MAT2A expression in human liver cancer, which facilitates cancer cell growth. The present work examined the role of methylation in MAT2A transcriptional regulation. We found that the human MAT2A promoter is hypomethylated in hepatocellular carcinoma, in which the gene is upregulated transcriptionally, but hypermethylated in normal liver, in which the gene is minimally expressed. Luciferase activities driven by in vitro methylated MAT2A promoter constructs were 75-95% lower than activities driven by unmethylated constructs. SAM treatment of Hep G2 cells reduced MAT2A endogenous expression by 75%, hypermethylated the MAT2A promoter, and reduced luciferase activities driven by MAT2A promoter constructs by 65-75% while not affecting MAT1A's promoter activity. Treatment of adult rat and human hepatocytes with trichostatin A, an inhibitor of histone deacetylase, upregulated MAT2A expression by more than fourfold. Collectively, these results suggest that MAT2A expression is regulated by promoter methylation and histone acetylation. PMID- 11208540 TI - Swallowing reflex and brain stem neurons activated by superior laryngeal nerve stimulation in the mouse. AB - The purpose of the present study was to identify vagal subnuclei that participate in reflex swallowing in response to electrical stimulation of the left superior laryngeal nerve (SLN). SLN stimulation at 10 Hz evoked primary peristalsis, including oropharyngeal and esophageal peristalsis, and LES relaxation. It also induced c-fos expression in interneurons in the interstitial (SolI), intermediate (SolIM), central (SolCe), dorsomedial (SolDM) and commissural (SolC) solitary subnuclei. Neurons in parvicellular reticular nucleus (PCRt) and area postrema (AP) and motoneurons in the semicompact (NAsc), loose (NAl), and compact (NAc) formations of the nucleus ambiguus and both rostral (DMVr) and caudal (DMVc) parts of the dorsal motor nucleus of vagus were also activated. The activated neurons represent all neurons concerned with afferent SLN-mediated reflexes, including the swallowing-related neurons. SLN stimulation at 5 Hz elicited oropharyngeal and LES but not esophageal responses and evoked c-fos expression in neurons in SolI, SolIM, SolDM, PCRt, AP, NAsc, NAl, and DMVc but not in SolCe, NAc, or DMVr. These data are consistent with the role of SolI, SolIM, SolDM, NAsc, NAl, and DMVc circuit in oropharyngeal peristalsis and LES relaxation and SolCe, NAc, DMVc, and DMVr in esophageal peristalsis and LES responses. PMID- 11208541 TI - Effects of nutrients and serotonin 5-HT3 antagonism on symptoms evoked by distal gastric distension in humans. AB - Distal gastric distension may contribute to meal-related dyspeptic symptoms. This study's aims were to determine the effects of distinct nutrient classes on symptoms induced by distal gastric distension and their dependence on 5 hydroxytryptamine(3) (5-HT3) receptors. Nine healthy subjects rated pain, nausea, and bloating induced by isobaric distal gastric distensions (6-24 mmHg) during duodenal lipid, carbohydrate, protein, or saline perfusion after treatment with placebo or the 5-HT3 receptor antagonist granisetron (10 microg/kg iv). Distensions produced greater pain, nausea, and bloating with lipid at 1.5 kcal/min compared with saline (P < or = 0.02), primarily because of greater distal gastric volumes at each distending pressure. In contrast, carbohydrate and protein had no significant effect. At 3 kcal/min, lipid increased symptoms through a volume-independent as well as a volume-dependent effect. Granisetron did not affect symptom perception or gastric pressure-volume relationships. In conclusion, isobaric distal gastric distension produces more intense symptoms during duodenal lipid compared with saline perfusion. Symptom perception during distal gastric distension is unaffected by 5-HT3 receptor antagonism. PMID- 11208542 TI - Diurnal rhythmicity in intestinal SGLT-1 function, V(max), and mRNA expression topography. AB - Mechanisms underlying the circadian rhythmicity in intestinal sugar absorption remain unclear. To test whether this rhythmicity is caused by changes in Na(+) glucose cotransporter 1 (SGLT-1) function, we measured phloridzin-inhibitable sugar fluxes as an index of SGLT-1 activity. Jejunum obtained from rats killed at 6-h intervals during a 12-h light-dark cycle (CT0 is circadian time 0 h, time of light onset) were mounted in Ussing chambers, and 3-O-methylglucose (3-OMG) fluxes were calculated before and after addition of phloridzin. 3-OMG-induced change in short-circuit current and absorptive flux were significantly greater at CT9 than at CT3. This increase was phloridzin inhibitable. Kinetic studies indicated a significant increase in SGLT-1 maximal velocity (V(max)) at CT9. Food intake between CT3 and CT9 was <10% of the daily total, indicating that the increased SGLT-1 activity was anticipatory. Diurnicity of SGLT-1 mRNA was confirmed by Northern blotting. Expression topography analyzed by in situ hybridization revealed more intense labeling along the entire villus axis at CT9 and CT15 compared with CT3 and CT21. We conclude that diurnicity in intestinal sugar absorption is caused by periodicity in SGLT-1 V(max). PMID- 11208543 TI - Effect of E. coli heat-stable enterotoxin on colonic transport in guanylyl cyclase C receptor-deficient mice. AB - We studied the functional importance of the colonic guanylyl cyclase C (GCC) receptor in GCC receptor-deficient mice. Mice were anesthetized with pentobarbital sodium, and colon segments were studied in Ussing chambers in HCO3- Ringer under short-circuit conditions. Receptor-deficient mouse proximal colon exhibited similar net Na+ absorption, lower net Cl- absorption, and a negative residual ion flux (J(R)), indicating net HCO3- absorption compared with that in normal mice. In normal mouse proximal colon, mucosal addition of 50 nM Escherichia coli heat-stable enterotoxin (STa) increased the serosal-to-mucosal flux of Cl- (J(s-->m)(Cl)) and decreased net Cl- flux (J(net)(Cl)) accompanied by increases in short-circuit current (I(sc)), potential difference (PD), and tissue conductance (G). Serosal STa had no effect. In distal colon neither mucosal nor serosal STa affected ion transport. In receptor-deficient mice, neither mucosal nor serosal 500 nM STa affected electrolyte transport in proximal or distal colon. In these mice, 1 mM 8-bromo-cGMP produced changes in proximal colon J(s- >m)(Cl) and J(net)(Cl), I(sc), PD, G, and J(R) similar to mucosal STa addition in normal mice. We conclude that the GCC receptor is necessary in the mouse proximal colon for a secretory response to mucosal STa. PMID- 11208544 TI - Involvement of PI 3-kinase in IGF-I stimulation of jejunal Na+-K+-ATPase activity and nutrient absorption. AB - Mechanisms responsible for increased jejunal transport rates observed in tissues treated with orally administered insulin-like growth factor-I (IGF-I) were studied in 5-day-old colostrum-deprived piglets. Human recombinant IGF-I (3.5 mg. kg(-1). day(-1)) or control vehicle was given orogastrically for 4 days. Disaccharidase activity, fructose uptake, and Na+-glucose cotransporter SGLT-1 protein abundance were similar between groups. Oral IGF-I produced greater rates of enterocyte Na+-K+-ATPase activity with no significant differences in Na+-K+ ATPase abundance. Cellular mechanisms responsible for transport changes were studied in Ussing chambers. In control tissues, the presence of IGF-I in mucosal solutions increased basal short-circuit current (I(sc)), potential difference, D glucose-stimulated I(sc), and Na+-K+-ATPase activity; these changes were abolished by preincubation of tissues with wortmannin, a phosphatidylinositol 3 kinase (PI 3-kinase) inhibitor. The results suggest that the effect of IGF-I on jejunal ion and nutrient transport involves activation of PI 3-kinase and stimulation of Na+-K+-ATPase activity in enterocytes. PMID- 11208545 TI - Insulin signal transduction in rat small intestine: role of MAP kinases in expression of mucosal hydrolases. AB - The postreceptor events regulating the signal of insulin downstream in rat intestinal cells have not yet been analyzed. Our objectives were to identify the nature of receptor substrates and phosphorylated proteins involved in the signaling of insulin and to investigate the mechanism(s) by which insulin enhances intestinal hydrolases. In response to insulin, the following proteins were rapidly phosphorylated on tyrosine residues: 1) insulin receptor substrates 1 (IRS-1), -2, and -4; 2) phospholipase C-isoenzyme-gamma; 3) the Ras-GTPase activating protein (GAP) associated with Rho GAP and p62(Src); 4) the insulin receptor beta-subunit; 5) the p85 subunits of phosphatidylinositol 3-kinase (PI 3 kinase); 6) the Src homology 2 alpha-collagen protein; 7) protein kinase B; 8) mitogen-activated protein (MAP) kinase-1 and -2; and 9) growth receptor-bound protein-2. Compared with controls, insulin enhanced the intestinal activity of MAP kinase-2 and protein kinase B by two- and fivefold, respectively, but did not enhance p70/S6 ribosomal kinase. Administration of an antireceptor antibody or MAP-kinase inhibitor PD-98059 but not a PI 3-kinase inhibitor (wortmannin) to sucklings inhibited the effects of insulin on mucosal mass and enzyme expression. We conclude that normal rat enterocytes express all of the receptor substrates and mediators involved in different insulin signaling pathways and that receptor binding initiates a signal enhancing brush-border membrane hydrolase, which appears to be regulated by the cascade of MAP kinases but not by PI 3-kinase. PMID- 11208546 TI - Isolation of functional polarized bile duct units from mouse liver. AB - The development of genetically altered murine animals has generated a need for in vitro systems in the mouse. We have now characterized a novel isolated bile duct unit (IBDU) preparation from the mouse to facilitate such studies. The mouse IBDU is isolated by portal perfusion of collagenase, blunt dissection, further enzymatic digestions, filtering through sized mesh, and culturing on Matrigel for 16-72 h. This mouse IBDU forms a central, enclosed lumen lined by polarized cytokeratin-19-positive cholangiocytes with numerous microvilli on the apical membrane. The IBDU responds to secretory stimuli, including secretin, vasoactive intestinal peptide, IBMX, and forskolin, resulting in expansion of the central lumen from secretion as quantified by videomicroscopy. The secretory response to secretin is dependent on Cl- and HCO3-in the perfusate. These findings indicate that mouse IBDUs are intact, polarized, functional bile duct secretory units that permit quantitative measurements of fluid secretion from mouse bile duct epithelium for the first time. This method should facilitate studies of cholangiocyte secretion in genetically altered murine animal models. PMID- 11208547 TI - Role of sodium/hydrogen exchanger isoform NHE3 in fluid secretion and absorption in mouse and rat cholangiocytes. AB - Na+/H+ exchanger (NHE) isoforms play important roles in intracellular pH regulation and in fluid absorption. The isoform NHE3 has been localized to apical surfaces of epithelia and in some tissues may facilitate the absorption of NaCl. To determine whether the apical isoform NHE3 is present in cholangiocytes and to examine whether it has a functional role in cholangiocyte fluid secretion and absorption, immunocytochemical studies were performed in rat liver with NHE3 antibodies and functional studies were obtained in isolated bile duct units from wild-type and NHE3-/- mice after stimulation with forskolin, using videomicroscopic techniques. Our results indicate that NHE3 protein is present on the apical membranes of rat cholangiocytes and on the canalicular membrane of hepatocytes. Western blots also detect NHE3 protein in rat cholangiocytes and isolated canalicular membranes. After stimulation with forskolin, duct units from NHE3-/- mice fail to absorb the secreted fluid from the cholangiocyte lumen compared with control animals. Similar findings were observed in isolated bile duct units from wild-type mice and rats in the presence of the Na+/H+ exchanger inhibitor 5-(N-ethyl-N-isopropyl)-amiloride. In contrast, we could not demonstrate absorption of fluid from the canalicular lumen of mouse or rat hepatocyte couplets after stimulation of secretion with forskolin. These findings indicate that NHE3 is located on the apical membrane of rat cholangiocytes and that this NHE isoform can function to absorb fluid from the lumens of isolated rat and mouse cholangiocyte preparations. PMID- 11208548 TI - Gender influence on jejunal migrating motor complex. AB - The role of gender and the menstrual cycle in small bowel motility has not been clearly elucidated. Jejunal motility was recorded with a nasojejunal catheter incorporating five solid-state pressure transducers in ambulatory menstruating women and men of comparable age over 24 h. All women were studied twice, in the early follicular (early-F) and midluteal (mid-L) phases of the menstrual cycle, verified by determining serum levels of gonadal steroids and gonadotropins. The propagation velocity of phase III was slow and the contraction amplitude was high in both menstrual cycle phases compared with men, and these parameters were correlated with serum estrogen levels in the mid-L phase. In the early-F phase, migrating motor complex (MMC) cycle duration during sleep was long compared with other groups and positively correlated with estrogen concentrations, whereas in the mid-L phase MMC cycle duration during sleep was negatively correlated with serum progesterone levels. In all groups, the frequency of phase III contractions was low and the intercontractile interval measured from pressure peak to peak was long during sleep compared with the awake state. Postprandial motility did not display gender difference in any parameter examined. The results demonstrate that the majority of patterns of motility are similar in menstruating women and men, whereas certain aspects of the MMC, most conspicuously propagation velocity and phase III contraction amplitude, differ. We have also documented circadian variation of phase III contraction frequency in both women and men. PMID- 11208549 TI - Apical and basolateral EGF receptors regulate gastric mucosal paracellular permeability. AB - Previous studies found that monolayers formed from canine oxyntic epithelial cells in primary culture displayed remarkable resistance to apical acidification and both mitogenic and migratory responses to epidermal growth factor (EGF) treatment. In our present studies, we found that EGF increased transepithelial resistance (TER) but not short-circuit current in these monolayers. Parallel effects of EGF on decreasing mannitol flux and increasing TER implicate direct regulation of paracellular permeability. EGF acting at either apical and basolateral receptors rapidly increased TER, but the apical response was sustained whereas the basolateral response was transient. (125)I-labeled EGF binding revealed specific apical binding, but receptor numbers were 25-fold lower than on the basolateral surface. Both apical and basolateral EGF activated tyrosine phosphorylation of EGF receptors (EGFR), beta-catenin, and cellular substrate as evident on confocal microscopy. Although apical EGF activated a lesser degree of receptor autophosphorylation than basolateral EGF, phosphorylation of beta-catenin was equally prominent with apical and basolateral receptor activation. Together, these findings indicate that functional apical and basolateral EGFR exist on primary canine gastric epithelial cells and that these receptors regulate paracellular permeability. The sustained effect of apical EGFR activation and prominent phosphorylation of beta-catenin suggest that apical EGFR may play a key role in this regulation. PMID- 11208550 TI - Circadian coupling between pancreatic secretion and intestinal motility in humans. AB - Human interdigestive intestinal motility follows a circadian rhythm with reduced nocturnal activity, but circadian pancreatic exocrine secretion is unknown. To determine whether circadian changes in interdigestive pancreatic secretion occur and are associated with motor events, pancreatic enzyme outputs, proximal jejunal motility, and plasma pancreatic polypeptide concentrations were measured during consecutive daytime and nighttime periods (12 h each) in seven healthy volunteers using orojejunal multilumen intubation. Studies were randomly started in the morning or evening. Nocturnally, motility decreased (motor quiescence: 67 +/- 22 vs. 146 +/- 37 min; motility index: 3.59 +/- 0.33 vs. 2.78 +/- 0.40 mmHg/min; both P < 0.05) but amylase output increased (273 +/- 78 vs. 384 +/- 100 U/min; P < 0.05) and protease output remained unchanged (P > 0.05); consequently, enzyme/motility ratio increased. Amylase outputs were always lowest during phase I. Motor but not pancreatic circadian activities were associated with sleep. Pancreatic polypeptide plasma concentrations were unchanged. Consequently, intestinal motor and pancreatic exocrine functions may have different circadian rhythms, i.e., decreased motor and stable secretory activity during the night. However, the association between individual phases of interdigestive motor and secretory activity is preserved. The nocturnal increase in enzyme/motility ratio is probably not caused by increased cholinergic tone. PMID- 11208551 TI - Kupffer cell-initiated remote hepatic injury following bilateral hindlimb ischemia is complement dependent. AB - Intravital fluorescence microscopy was applied to the livers of male Wistar rats to test the hypothesis that complement mobilization stimulates Kupffer cells and subsequently initiates hepatic injury after hindlimb ischemia/reperfusion (I/R). Following 3 h of limb reperfusion, hepatocellular viability (serum levels of alanine transaminase and cell death via propidium iodide labeling) decreased significantly from levels in sham-operated animals. Inhibition of complement mobilization with soluble complement receptor type 1 (20 mg/kg body wt) and interruption of Kupffer cell function with GdCl(3) (1 mg/100g body wt) resulted in significant hepatocellular protection. Although the effects of hindlimb I/R on hepatic microvascular perfusion were manifest as increased heterogeneity, both complement inhibition and suppression of Kupffer cell function resulted in marked improvements. No additional hepatocellular protection and microvascular improvements were provided by combining the interventions. Furthermore, inhibition of complement mobilization significantly depressed Kupffer cell phagocytosis by 42% following limb reperfusion. These results suggest that the stimulation of Kupffer cells via complement mobilization is necessary but is not the only factor contributing to the early pathogenesis of hepatic injury following hindlimb I/R. PMID- 11208552 TI - Epithelial calcium transporter expression in human duodenum. AB - Calcium absorption in intestine and kidney involves transport through the apical membrane, cytoplasm, and basolateral membrane of the epithelial cells. Apical membrane calcium influx channels have recently been described in rabbit (epithelial calcium channel, ECaC) and rat (calcium transport protein, CaT1). We amplified from human duodenum a 446-base partial cDNA probe (ECAC2) having a predicted amino acid similarity of 97% to rat CaT1. Duodenum, but not ileum, colon, or kidney, expressed a 3-kb transcript. A larger transcript was also found in placenta and pancreas, and a different, faint transcript was found in brain. In duodenal biopsies from 20 normal volunteers, expression varied considerably but was not significantly correlated with vitamin D metabolites. This signal correlated with calbindin-D(9k) (r = 0.48, P < 0.05) and more strongly with the plasma membrane calcium ATPase PMCA1 (r = 0.83, P < 0.001). These data show that although individual variations in calcium channel transcripts are not vitamin D dependent, expression of genes governing apical entry and basolateral extrusion are tightly linked. This may account for some of the unexplained variability in calcium absorption. PMID- 11208553 TI - Endothelial E- and P-selectin expression in iNOS- deficient mice exposed to polymicrobial sepsis. AB - In vitro, nitric oxide (NO) decreases leukocyte adhesion to endothelium by attenuating endothelial adhesion molecule expression. In vivo, lipopolysaccharide induced leukocyte rolling and adhesion was greater in inducible NO synthase (iNOS)-/- mice than in wild-type mice. The objective of this study was to assess E- and P-selectin expression in the microvasculature of iNOS-/- and wild-type mice subjected to acute peritonitis by cecal ligation and perforation (CLP). E- and P-selectin expression were increased in various organs within the peritoneum of wild-type animals after CLP. This CLP-induced upregulation of E- and P selectin was substantially reduced in iNOS-/- mice. Tissue myeloperoxidase (MPO) activity was increased to a greater extent in the gut of wild-type than in iNOS-/ mice subjected to CLP. In the lung, the reduced expression of E-selectin in iNOS /- mice was not associated with a decrease in MPO. Our findings indicate that NO derived from iNOS plays an important role in sepsis-induced increase in selectin expression in the systemic and pulmonary circulation. However, in iNOS-/- mice, sepsis-induced leukocyte accumulation is affected in the gut but not in the lungs. PMID- 11208554 TI - Molecular mechanisms for the antiapoptotic action of gastrin. AB - Gastrin (G17) has a CCK-B receptor-mediated growth-promoting effect on the AR42J rat acinar cell line. We examined whether G17 inhibits apoptosis induced by serum withdrawal of AR42J cells and CHO-K1 cells stably expressing CCK-B receptors (CHO K1/CCK-B cells). Cellular apoptosis was measured by flow cytometry and the terminal deoxynucleotidyltransferase-mediated dUTP-FITC nick end-labeling method. Serum withdrawal induced AR42J and CHO-K1/CCK-B cell apoptosis. Addition of 10 nM G17 reversed these effects. We examined the action of G17 (10 nM) on phosphorylation and activation of protein kinase B/Akt, a kinase known to promote cell survival. Akt phosphorylation and activation were measured by kinase assays and Western blots with an anti-phospho-Akt antibody. G17 stimulated Akt phosphorylation and activation. G17 induction of Akt phosphorylation was inhibited by the phosphoinositide 3-kinase (PI 3-kinase) inhibitors LY-294002 (10 microM) and wortmannin (200 nM) but not by the mitogen-activated protein kinase kinase 1 inhibitor PD-98059 (50 microM). To study the role of p38 kinase in G17 signaling to Akt, we examined the effect of G17 on p38 kinase activation and phosphorylation using kinase assays and Western blots with an anti-phospho-p38 kinase antibody. G17 induced p38 kinase activity at doses and with kinetics similar to those observed for Akt induction. The p38 kinase inhibitor SB-203580 inhibited G17 induction of Akt phosphorylation and activation at a concentration (10 microM) 10-fold higher than necessary to block p38 kinase (1 microM), suggesting the possible involvement of kinase activities other than p38 kinase. Transduction of AR42J cells with the adenoviral vector Adeno-dn Akt, which overexpresses an inhibitor of Akt, reversed the antiapoptotic action of G17. In conclusion, G17 promotes AR42J cell survival through the induction of Akt via PI 3-kinase and SB-203580-sensitive kinase activities. PMID- 11208555 TI - Neuronal nitric oxide synthase: expression in rat parietal cells. AB - Nitric oxide synthases (NOS) are enzymes that catalyze the generation of nitric oxide (NO) from L-arginine and require nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor. At least three isoforms of NOS have been identified: neuronal NOS (nNOS or NOS I), inducible NOS (iNOS or NOS II), and endothelial NOS (eNOS or NOS II). Recent studies implicate NO in the regulation of gastric acid secretion. The aim of the present study was to localize the cellular distribution and characterize the isoform of NOS present in oxyntic mucosa. Oxyntic mucosal segments from rat stomach were stained by the NADPH diaphorase reaction and with isoform-specific NOS antibodies. The expression of NOS in isolated, highly enriched (>98%) rat parietal cells was examined by immunohistochemistry, Western blot analysis, and RT-PCR. In oxyntic mucosa, histochemical staining revealed NADPH-diaphorase and nNOS immunoreactivity in cells in the midportion of the glands, which were identified as parietal cells in hematoxylin and eosin-stained step sections. In isolated parietal cells, decisive evidence for nNOS expression was obtained by specific immunohistochemistry, Western blotting, and RT-PCR. Cloning and sequence analysis of the PCR product confirmed it to be nNOS (100% identity). Expression of nNOS in parietal cells suggests that endogenous NO, acting as an intracellular signaling molecule, may participate in the regulation of gastric acid secretion. PMID- 11208556 TI - Evolution of the Na-P(i) cotransport systems. AB - Membrane transport systems for P(i) transport are key elements in maintaining homeostasis of P(i) in organisms as diverse as bacteria and human. Two Na-P(i) cotransporter families with well-described functional properties in vertebrates, namely NaPi-II and NaPi-III, show conserved structural features with prokaryotic origin. A clear vertical relationship can be established among the mammalian protein family NaPi-III, a homologous system in C. elegans, the yeast system Pho89, and the bacterial P(i) transporter Pit. An alternative lineage connects the mammalian NaPi-II-related transporters with homologous proteins from Caenorhabditis elegans and Vibrio cholerae. The present review focuses on the molecular evolution of the NaPi-II protein family. Preliminary results indicate that the NaPi-II homologue cloned from V. cholerae is indeed a functional P(i) transporter when expressed in Xenopus oocytes. The closely related NaPi-II isoforms NaPi-IIa and NaPi-IIb are responsible for regulated epithelial Na dependent P(i) transport in all vertebrates. Most species express two different NaPi-II proteins with the exception of the flounder and Xenopus laevis, which rely on only a single isoform. Using an RT-PCR-based approach with degenerate primers, we were able to identify NaPi-II-related mRNAs in a variety of vertebrates from different families. We hypothesize that the original NaPi-IIb related gene was duplicated early in vertebrate development. The appearance of NaPi-IIa correlates with the development of the mammalian nephron. PMID- 11208557 TI - Role of non-NMDA receptors in vasopressin and oxytocin release from rat hypothalamo-neurohypophysial explants. AB - Glutamate is recognized as a prominent excitatory transmitter in the supraoptic nucleus (SON) and is involved in transmission of osmoregulatory information from the osmoreceptors to the vasopressin (VP) and oxytocin (OT) neurons. Explants of the hypothalamo-neurohypophysial system were utilized to characterize the roles of the non-N-methyl-D-aspartate (NMDA) glutamate receptor subtypes (non-NMDA-Rs), kainic acid receptors (KA-Rs), and aminopropionic acid receptors (AMPA-Rs) and to evaluate the interdependence of NMDA-Rs and non-NMDA-Rs in eliciting hormone release. Although both KA and AMPA increased hormone release, a specific agonist of the KA-Rs, SYM-2081, was not effective. This combined with the finding that cyclothiazide, an agent that inhibits the desensitization of AMPA-Rs, increased the VP response to both KA and AMPA indicates that the increase in hormone release induced by the non-NMDA agonists is mediated via AMPA-Rs, rather than KA Rs. Inhibition of osmotically stimulated VP and OT release by a specific AMPA-R antagonist indicated that AMPA-Rs are essential for mediating osmotically stimulated hormone release. NMDA-stimulated VP but not OT release was prevented by blockade of non-NMDA-Rs, but AMPA-stimulated VP/OT release was not prevented by NMDA-R blockade. PMID- 11208558 TI - Cytoskeletal protein contents before and after hindlimb suspension in a fast and slow rat skeletal muscle. AB - Transversal cytoskeletal organization of muscle fibers is well described, although very few data are available concerning protein content. Measurements of desmin, alpha-actinin, and actin contents in soleus and extensor digitorum longus (EDL) rat skeletal muscles, taken with the results previously reported for several dystrophin-glycoprotein complex (DGC) components, indicate that the contents of most cytoskeletal proteins are higher in slow-type fibers than in fast ones. The effects of hypokinesia and unloading on the cytoskeleton were also investigated, using hindlimb suspension. First, this resulted in a decrease in contractile protein contents, only after 6 wk, in the soleus. Dystrophin and associated proteins were shown to be reduced for soleus at 3 wk, whereas only the dystrophin-associated proteins were found to increase after 6 wk. On the other hand, the contents of DGC components were increased for EDL for the two durations. Desmin and alpha-actinin levels were unchanged in the same conditions. Consequently, it can be concluded that the cytoskeletal protein expression levels could largely contribute to muscle fiber adaptation induced by modified functional demands. PMID- 11208559 TI - Diminished satiation in rats exposed to elevated levels of endogenous or exogenous cholecystokinin. AB - Rats maintained on a high-fat (HF) diet exhibit reduced sensitivity to the satiation-producing effect of exogenous CCK. Because more CCK is released in response to HF meals than low-fat (LF) meals, we hypothesized that increased circulating CCK associated with ingestion of HF diets contributes to the development of decreased CCK sensitivity. To test this hypothesis, we implanted osmotic minipumps filled with either NaCl or CCK octapeptide into the peritoneal cavity. Subsequently, we examined the effect of intraperitoneal NaCl or CCK (0.5 microg/kg) injection on 30-min food intake. CCK significantly reduced 30-min food intake less in rats implanted with CCK-releasing minipumps compared with those with NaCl-releasing minipumps. Because dietary protein is a potent releaser of endogenous CCK, we hypothesized that rats adapted to a high-protein (HP) diet might also exhibit reduced sensitivity to exogenous CCK. Therefore, in a second experiment, we examined CCK-induced reduction of food intake in rats maintained on LF and rats maintained on HF or HP. Ingestion of LF stimulates very little endogenous CCK secretion, whereas both HF and HP markedly increase plasma CCK concentrations. Both doses of CCK reduced food intake significantly less in HF and HP rats compared with LF rats. There were no differences in 24-h food intake, body weight, or body fat composition among LF-, HF-, and HP-fed rats. These results are consistent with the hypothesis that sustained elevation of CCK either by infusion of exogenous CCK or by dietary-induced elevation of plasma CCK contributes to the development of reduced sensitivity to exogenous CCK. PMID- 11208561 TI - Hypoalgesia and hyperalgesia with inherited hypertension in the rat. AB - Many studies indicate that blood pressure control systems can attenuate pain (hypoalgesia) of short duration; however, we recently found exaggerated nociceptive responses (hyperalgesia) of persistent duration in the spontaneously hypertensive rat (SHR). Here, we used SHR, Dahl Salt-Sensitive (SS), and normotensive control rats to evaluate the contribution of sustained elevations in arterial pressure to nociceptive responses. Compared with Sprague-Dawley and/or Wistar-Kyoto controls, SHR were 1) hypoalgesic in the hot plate test and 2) hyperalgesic in longer latency tail and paw-withdrawal tests and in two models of inflammatory nociception. These differences were not observed between SS and salt resistant controls fed a high-salt diet. Inflammatory hyperalgesia in SHR was correlated with neither paw edema nor the number of Fos-positive spinal cord neurons. Our results indicate that "pain" phenotype of the SHR is not restricted to hypoalgesia. This phenotype is related to genetic factors or to the autonomic systems that control blood pressure and not to sustained elevations in blood pressure, differences in spinal neuron activity, or inflammatory edema. PMID- 11208560 TI - Effect of heat stress on LPS-induced febrile response in D-galactosamine sensitized rats. AB - We have previously reported that heat conditioning augments lipopolysaccharide (LPS)-induced fever in rats, which is accompanied by an accumulation of heat shock protein (HSP) in the liver and the reduction of the plasma level of tumor necrosis factor (TNF-alpha) (Kluger MJ, Rudolph K, Soszynski D, Conn CA, Leon LR, Kozak W, Wallen ES, and Moseley PL. Am J Physiol Regulatory Integrative Comp Physiol 273: R858-R863, 1997). In the present study we have tested whether inhibition of protein synthesis in the liver can reduce the effect of this heat conditioning on the LPS-induced febrile response in the rat. D-galactosamine (D gal) was used to selectively inhibit liver protein synthesis. D-gal (500 mg/kg) or PBS as control was administered intraperitoneally 1 h before heat stress. LPS (50 microg/kg ip) was injected 24 h post-heat exposure. Treatment with D-gal blunted the febrile response to LPS. Moreover, heat-conditioned rats treated first with D-gal and subsequently with LPS demonstrated a profound fall in core temperature 10--18 h post-LPS. A significant increase of serum TNF-alpha accompanied this effect of D-gal on fever. Heat-conditioned animals receiving D gal showed an inhibition in inducible HSP-70 in the liver. These data support the role of hepatic function in modulating the febrile response to LPS. PMID- 11208562 TI - Functional desensitization to isoproterenol without reducing cAMP production in canine failing cardiocytes. AB - To corroborate alterations in the functional responses to beta-adrenergic receptor (beta-AR) stimulation with changes in beta-AR signaling in failing cardiomyocytes, contractile and L-type Ca(2+) current responses to isoproterenol along with stimulated cAMP generation were compared among cardiomyocytes isolated from canines with tachycardia-induced heart failure or healthy hearts. The magnitude of shortening of failing cardiomyocytes was significantly depressed (by 22 +/- 4.4%) under basal conditions, and the maximal response to isoproterenol was significantly reduced (by 45 +/- 18%). Similar results were obtained when the responses in the rate of contraction and rate of relaxation to isoproterenol were considered. The L-type Ca(2+) current amplitude measured in failing cardiomyocytes under basal conditions was unchanged, but the responses to isoproterenol were significantly reduced compared with healthy cells. Isoproterenol-stimulated cAMP generation was similar in sarcolemmal membranes derived from the homogenates of failing (45 +/- 6.8) and healthy cardiomyocytes (52 +/- 8.5 pmol cAMP. mg protein(-1). min(-1)). However, stimulated cAMP generation was found to be significantly reduced when the membranes were derived from the homogenates of whole tissue (failing: 67 +/- 8.1 vs. healthy: 140 +/- 27.8 pmol cAMP. mg protein(-1). min(-1)). Total beta-AR density was not reduced in membranes derived from either whole tissue or isolated cardiomyocyte homogenates, but the beta(1)/beta(2) ratio was significantly reduced in the former (failing: 45/55 vs. healthy: 72/28) without being altered in the latter (failing: 72/28, healthy: 77/23). We thus conclude that, in tachycardia-induced heart failure, reduction in the functional responses of isolated cardiomyocytes to beta-AR stimulation may be attributed to alterations in the excitation contraction machinery rather than to limitation of cAMP generation. PMID- 11208563 TI - Expression of carbonic anhydrase IV in mouse placenta. AB - Carbonic anhydrase (CA) facilitates acid-base transport in several tissues. Acidosis upregulates membrane-bound SDS-resistant hydratase activity in various tissues and CA IV mRNA in rabbit kidney. This study was designed to assess whether the expression of membrane-bound CA IV isozyme in mouse placenta is regulated developmentally and by maternal ammonium chloride loading at the end of pregnancy. For this purpose we used Northern blot analysis, Western blots of microsomal membranes, and immunocytochemistry. The expression of CA IV mRNA on Northern blots tripled from day 11 to day 15 and then remained stable until the end of pregnancy. Expression of CA IV immunoreactive protein on Western blot tripled from day 11 to day 15 and decreased almost to baseline by day 19. Strong staining for CA IV was detected by immunocytochemistry in labyrinthine trophoblast, in the endodermal layer of the yolk sac (both intra- and extraplacental) and in the uterine epithelium. Weak staining was observed in most fetal endothelial cells at 11 days but not later in gestation. Maternal acidosis did not upregulate the expression of CA IV mRNA or CA IV immunoreactive protein. Thus CA IV expression in mouse placenta is developmentally regulated. Maternal acidosis during the last quarter of pregnancy does not upregulate CA IV mRNA or CA IV immunoreactive protein. PMID- 11208564 TI - Organ-specific distribution of AP-1 in AP-1 luciferase transgenic mice during the maturation process. AB - Activator protein-1 (AP-1), a dimeric complex consisting of proteins encoded by the jun and fos gene families, is a transcription factor induced by a variety of signals including those eliciting proliferation, differentiation, and neoplastic transformation. Although AP-1 has been widely studied in the last decade, physiological levels of AP-1 in different tissues are unclear. In the present study, we analyzed AP-1 activity in several organs (liver, kidney, brain, lung, spleen, heart, skin) of AP-1-luciferase transgenic mice of various ages. Results of these studies indicate that the level of AP-1 in young mice is much higher than that in older mice, and, second, that the skin contains considerably higher levels of AP-1 than other organs. The level of phosphorylated extracellular signal-regulated protein kinase (ERK) in skin was higher in 1- and 2-day-old mice than in mice of other ages. In addition, phosphorylated p38 kinase was high in 2 day-old and 1-wk-old mice, but phosphorylated c-Jun NH(2)-terminal kinase was not detected at any age. AP-1 activity and level of phosphorylated ERKs declined with maturation. These results imply that AP-1 activity mediated through an ERKs dependent pathway may be involved in skin development. PMID- 11208565 TI - The small intestine plays an important role in upregulating CGRP during sepsis. AB - Although studies have indicated that calcitonin gene-related peptide (CGRP), a potent vasodilatory peptide, is upregulated after endotoxic shock, it remains controversial whether this peptide increases during sepsis and, if so, whether the gut is a significant source of CGRP under such conditions. To study this, polymicrobial sepsis was induced by cecal ligation and puncture (CLP) followed by fluid resuscitation. Plasma levels of CGRP were measured at 2, 5, and 10 h after CLP (i.e., early, hyperdynamic sepsis) and at 20 h after CLP (late, hypodynamic sepsis). The results indicate that plasma CGRP did not increase at 2--5 h but increased by 177% at 10 h after CLP (P < 0.05). At 20 h after the onset of sepsis, however, the elevated plasma CGRP returned to the sham level. To determine the source of the increased plasma CGRP, the liver, spleen, small intestine, lungs, and heart were harvested, and tissue CGRP was assayed at 10 h after CLP in additional animals. Only the small intestine showed a significant increase in tissue levels of CGRP (by 129%, P < 0.05). Determination of portal vs. systemic levels of CGRP indicates that portal CGRP was 65.7 +/- 22.7% higher than the systemic level at 10 h after CLP, whereas portal CGRP in sham-operated rats was only 4.9 +/- 2.1% higher. Immunohistochemistry examination revealed that CGRP-positive stainings increased in the intestinal tissue but not in the liver at 10 h after the onset of sepsis. The distribution of CGRP stainings was associated with intestinal nerve fibers. These results, taken together, demonstrate that upregulation of CGRP occurs transiently during the progression of sepsis (at the late phase of the hyperdynamic sepsis), and the gut appears to be a major source of such an increase in circulating levels of this peptide. PMID- 11208566 TI - Chronic exercise alters caudal hypothalamic regulation of the cardiovascular system in hypertensive rats. AB - Previous studies have documented a deficit in the GABA neurotransmitter system within the caudal hypothalamus (CH) of spontaneously hypertensive rats (SHR). The reduction in inhibitory influence on this cardiovascular excitatory brain region is associated with an increased neuronal activity and resting blood pressure. The purpose of this study was to determine if chronic treadmill and wheel-running activities alter the ability of the CH to regulate cardiovascular function. SHR were exercised on a treadmill (5 times/wk) at moderate intensity or allowed free access to running wheels (7 days/wk) for a period of 10 wk. Resting blood pressures were obtained before and after the exercise training periods. After the exercise period, rats were anesthetized and microinjection experiments were performed. Treadmill-trained SHR exhibited a significantly blunted developmental rise in resting blood pressure after 10 wk of exercise. A similar yet less marked effect was observed in wheel-run rats. Microinjection of the GABA synthesis inhibitor 3-mercaptopropionic acid (3-MP) into the CH of nonexercised SHR did not produce any change in arterial pressure. In contrast, microinjection of 3-MP into the CH produced significant increases in blood pressure and heart rate in exercised SHR. These results demonstrate that exercise training can alter CH cardiovascular regulation in hypertensive rats and therefore may play a role in increasing cardiovascular health. PMID- 11208567 TI - Sleep changes induced by lipopolysaccharide in the rat are influenced by age. AB - In mammals, aging is associated with immune senescense. To examine whether the sleep changes occurring during immune challenge are affected by age, we assessed sleep alterations induced by the administration of lipopolysaccharide (LPS) in young and middle-aged rats. During vehicle, the middle-aged rats exhibited less pre-rapid eye movement sleep (pre-REMS) as well as REMS, due to a smaller number and shorter duration of REMS episodes, than young rats. LPS elevated body temperature, increased non-REMS, and suppressed both pre-REMS and REMS in the young as well as in the middle-aged rats. However, in the young animals, LPS significantly enhanced slow-wave activity in the electroencephalogram (EEG) within non-REMS, reflecting an increase in sleep intensity. In contrast, LPS attenuated EEG power in most frequency bands in the older animals. This finding indicates age-related changes in the modulation of sleep by LPS. PMID- 11208568 TI - Angiotensin-(1--7) in the ovine fetus. AB - In the adult animal, ANG-(1-7) may counterbalance some effects of ANG II. Its effects in the fetus are unknown. Basal ANG-(1-7), ANG I, ANG II, and renin concentrations were measured in plasma from ovine fetuses and their mothers (n = 10) at 111 days of gestation. In the fetus, concentrations of ANG I, ANG-(1-7), and ANG II were 86 +/- 21, 13 +/- 2, and 14 +/- 2 fmol/ml, respectively. In the ewe, concentrations of ANG I were significantly lower (20 +/- 4 fmol/ml, P < 0.05) as were concentrations of ANG-(1-7) (2.9 +/- 0.6 fmol/ml), whereas ANG II concentrations were not different (10 +/- 1 fmol/ml). Plasma renin concentrations were higher in the fetus (4.8 +/- 1.1 pmol ANG I x ml(-1) x h(-1)) than in the ewe (0.9 +/- 0.2 pmol x ml(-1) x h(-1), P < 0.05). Infusion of ANG-(1-7) (approximately 9 microg/h) for a 3-day period caused a significant increase in plasma concentrations of ANG-(1-7) reaching a maximum of 448 +/- 146 fmol/ml on day 3 of infusion. Plasma levels of ANG I and II as well as renin were unchanged by the infusion. Urine flow rate, glomerular filtration rate, and fetal arterial blood pressure did not change and were not different than values in fetuses receiving a saline infusion for 3 days (n = 5). However, the osmolality of amniotic and allantoic fluid was significantly higher in fetuses that received ANG-(1-7). Also, compared with the saline-infused animals, mRNA expression levels of renin, the AT(1) receptor, and AT(2) receptor were elevated in kidneys of fetuses that received infusions of ANG-(1-7). Infusion of an ANG-(1-7) antagonist ([D-Ala(7)]-ANG-(1-7), 20 microg/h) for 3 days had no effect on fetal blood pressure or renal function. In conclusion, although infusion of ANG-(1-7) did not affect fetal urine flow rate, glomerular filtration rate, or blood pressure, changes in fetal fluids and gene expression indicate that ANG-(1-7) may play a role in the fetal kidney. PMID- 11208569 TI - Effects of maturation and acute hypoxia on receptor-IP(3) coupling in ovine common carotid arteries. AB - Whereas previous studies have established that many mechanisms mediating pharmacomechanical coupling are subject to regulation, evidence of physiological regulation of the coupling efficiency between receptor activation and second messenger production is scarce. The present studies address the hypothesis that acute hypoxia and maturation can influence the mass of second-messenger production for each activated agonist-bound receptor ("receptor gain"). For this assessment, receptor density and agonist affinity values were used to calculate 5 hydroxytryptamine (5-HT) concentrations that would produce standardized numbers of bound receptors (8.5 fmol/mg protein) in each experimental group and thus minimize effects of age or hypoxia on receptor density or agonist affinity. After 3 min of exposure to these 5-HT concentrations, normoxic magnitudes of contraction were similar (as %potassium maxima) in fetal (50 +/- 14%) and adult (40 +/- 9%) arteries, but hypoxia (PO(2) approximately 9--12 Torr for 30 min) depressed contractile tensions with a significantly different time course and magnitude in fetal (30 +/- 10%) and adult (17 +/- 11%) arteries (P < 0.05). Basal inositol 1,4,5-trisphosphate (IP(3)) values (in pmol/mg protein) were significantly greater in fetal (94 +/- 16) than in adult (44 +/- 6) arteries, and integrated areas above baseline for the IP(3) time courses (in nmol-s/mg protein) were significantly greater in fetal than in adult arteries both in normoxic (14.3 +/- 1.8 vs. 9.1 +/- 1.6) and hypoxic (15.0 +/- 2.1 vs. 8.6 +/- 1.2) conditions (P < 0.05). Hypoxia altered the IP(3) time courses both in the fetus and the adult but had no significant effect on IP(3 )mobilization or receptor gain. These data demonstrate that for the 5-HT(2a) receptor predominant in this preparation, receptor gain can be experimentally determined, is not influenced by acute hypoxia, but is greater in fetal than in adult ovine carotid arteries. PMID- 11208570 TI - Effect of water restriction on feeding and metabolism in dairy cows. AB - We investigated how lactating cows are able to cope with a sustained water restriction. In experiment 1, body weight and meal patterns were recorded with ad libitum access to water (baseline) and during 8 days of 25 and 50% restriction of drinking water relative to ad libitum intake. In experiment 2, indirect calorimetry was combined with nitrogen and energy balance and plasma hormone and metabolite measurements to assess the effects of 50% water restriction on digestion and metabolism. In experiment 1, food intake and body weight declined during the first 3 days of water restriction depending on the restriction level and stabilized thereafter at a lower level. The daily food intake reduction with 50% water restriction was entirely due to a reduction of meal size. The size of the first meal on every day was markedly (>50%) reduced with 25 and 50% water restriction. In experiment 2, urea concentrations in milk and blood as well as plasma sodium and hematocrit were increased by 50% water restriction. Energy balance was not affected by 50% water restriction, but nitrogen balance became negative, because, relative to intake, nitrogen excretion via urine and milk was higher. The lower energy intake during 50% water restriction was compensated by a lower milk production, a higher digestibility of organic matter and energy, and, apparently, a more efficient energy use. Through these changes and a preserved water balance, the cows reached a new equilibrium at a lower water turnover level, which enabled them to cope with a sustained drinking water restriction of 50%. PMID- 11208571 TI - Alterations of the renin-angiotensin system at the RVLM of transgenic rats with low brain angiotensinogen. AB - The transgenic rats TGR(ASrAOGEN) (TGR) with low levels of brain angiotensinogen were analyzed for cardiovascular reactivity to microinjections of ANG II and angiotensin receptor (AT(1)) antagonists [CV-11974, AT(1) specific; A-779, ANG-(1 -7) selective; sarthran, nonspecific] into the rostral ventrolateral medulla (RVLM) of conscious rats. Microinjection of ANG II resulted in a significantly higher increase in the mean arterial pressure (MAP) of TGR than control [Sprague Dawley (SD)] rats, suggesting an upregulation of ANG II receptors in TGR. CV 11974 produced an increase in MAP of SD but not in TGR rats. A-779 produced a depressor response in SD but not in TGR rats. Conversely, sarthran produced a similar decrease of MAP in both rat groups. The pressor effect of the AT(1) antagonist may indicate an inhibitory role of AT(1) receptors in the RVLM. On the other hand, ANG-(1--7) appears to have a tonic excitatory role in this region. The altered response to specific angiotensin antagonists in TGR further supports the functionally relevant decrease in angiotensins in the brains of TGR and corroborates the importance of the central renin-angiotensin system in cardiovascular homeostasis. PMID- 11208572 TI - Glutamatergic and GABAergic inputs to the RVL mediate cardiovascular adjustments to noxious stimulation. AB - Stimulation of cutaneous and muscle afferents induces several cardiovascular adjustments such as hypertension, tachycardia, and muscle vasodilation. Although previous studies have demonstrated that the rostral ventrolateral medulla (RVL) mediates sympathoexcitation and pressor responses to sciatic nerve stimulation (SNS), whether it also mediates blood flow adjustments remains unclear. Therefore, in the present study, we examined the role of the RVL in the vasodilation induced by SNS and the possible neurotransmitters involved. In Urethane-anesthetized, paralyzed, and artificially ventilated rats, SNS (square pulses, 1 ms, 20 Hz, 800--1200 microA, 10 s) produced increases in blood pressure, heart rate, blood flow, and vascular conductance of the stimulated limb. Unilateral microinjection of kainic acid (2 nmol/100 nl) into the RVL contralateral to the stimulated limb abolished cardiovascular adjustments to SNS. Unilateral microinjections of kynurenic acid (2 nmol/100 nl) selectively abolished the pressor response to SNS, whereas bicuculline (400 pmol/100 nl) abolished the increases in blood flow without changing the pressor response. These results suggest that glutamatergic synapses within the RVL mediate pressor responses, whereas GABAergic synapses may mediate the vasodilation to SNS. PMID- 11208573 TI - Effect of acute exercise on citrate synthase activity in untrained and trained human skeletal muscle. AB - Maximal citrate synthase activity (CS) is routinely used as a marker of aerobic capacity and mitochondrial density in skeletal muscle. However, reported CS has been notoriously variable, even with similar experimental protocols and sampling from the same muscles. Exercise training has resulted in increases in CS ranging from 0 to 100%. Previously, it has been reported that acute exercise may significantly affect CS. To investigate the hypothesis that the large variation in CS that occurs with training is influenced by alterations during the exercise itself, we studied CS in human vastus lateralis both in the rested and acutely exercised state while trained and untrained (n = 6). Tissues obtained from four biopsies (untrained rested, untrained acutely exercised, trained rested, and trained acutely exercised) were analyzed spectrophotometrically for maximal CS. Exercise training measured in a rested state resulted in an 18.2% increase in CS (12.3 +/- 0.3 to 14.5 +/- 0.3 micromol x min(-1) x g tissue(-1), P < or = 0.05). However, even greater increases were recorded 1 h after acute exercise: 49.4% in the untrained state (12.3 +/- 0.3 to 18.3 +/- 0.5 micromol x min(-1) x g tissue( 1), P < or = 0.05) and 50.8% in the trained state (14.5 +/- 0.3 to 21.8 +/- 0.4 micromol x min(-1) x g tissue(-1), P < or = 0.05). Ultrastructural analysis, by electron microscopy, supported an effect of acute exercise with the finding of numerous swollen mitochondria 1 h after exercise that may result in greater access to the CS itself in the CS assay. In conclusion, although unexplained, the increased CS with acute exercise can clearly confound training responses and artificially elevate CS values. Therefore, the timing of muscle sampling relative to the last exercise session is critical when measuring CS and offers an explanation for the large variation in CS previously reported. PMID- 11208574 TI - Carbon monoxide is the heme oxygenase product with a pyretic action: evidence for a cGMP signaling pathway. AB - We have recently reported that the central heme oxygenase (HO) pathway has an important role in the genesis of lipopolysaccharide fever. However, the HO product involved, i.e., biliverdine, free iron, or carbon monoxide (CO), has not yet been identified with certainty. Therefore, in the present study, we tested the thermoregulatory effects of all HO products. Body core temperature (T(c)) and gross activity of awake, freely moving rats was measured by biotelemetry. Intracerebroventricular administration of heme-lysinate (152 nmol), which induces the HO pathway, evoked a marked increase in T(c), a response that was attenuated by intracerebroventricular pretreatment with the HO inhibitor zinc deuteroporphyrin 2,4-bis glycol (200 nmol), indicating that an HO product has a pyretic action in the central nervous system (CNS) of rats. Besides, heme lysinate also increased gross activity, but no correlation was found between this effect and the increase in T(c). Moreover, intracerebroventricular biliverdine or iron salts at 152 nmol, a dose at which heme-lysinate was effective in increasing T(c), produced no change in T(c). Accordingly, intracerebroventricular treatment with the iron chelator deferoxamine elicited no change in basal T(c) and did not affect heme-induced pyresis. However, heme-induced pyresis was completely prevented by the soluble guanylate cyclase (sGC) inhibitor 1H [1,2,4]oxadiazolo[4,3,-a]quinoxaline-1-one. Because biliverdine and iron had no thermoregulatory effects and CO produces most of its actions via sGC, these data strongly imply that CO is the only HO product with a pyretic action in the CNS. PMID- 11208576 TI - Topical application of the phospholipid growth factor lysophosphatidic acid promotes wound healing in vivo. AB - The lipid mediator lysophosphatidic acid (LPA) regulates cell proliferation and enhances cell motility in vitro, both of which are important events in wound healing. To evaluate the effects of LPA in vivo, it was applied to a full thickness wound of rat skin. LPA in micromolar concentrations, or solvent, was applied daily. Animals were killed at 1, 3, 6, and 9 days after wounding and processed for histological evaluation, including hematoxylin-eosin staining and histochemical markers for macrophage-histiocytes, proliferating cells, and capillary endothelial cells. LPA treatment accelerated wound closing and increased neoepithelial thickness. Cytological evaluation showed no evidence for a secondary inflammation-mediated injury, infection, or increased keloid formation. Whereas LPA caused only a modest dose-dependent increase in proliferating cells, a marked increase in the immigration of histiocyte macrophage cells was observed as early as day 1. The peaks of several cytological features and immunohistological markers preceded those of the untreated side. Our data suggest that exogenously applied LPA in this model promotes healing and that macrophage-histiocytes are the primary LPA-responsive cells in vivo. PMID- 11208575 TI - Vasopressin pressor receptor-mediated activation of HPA axis by acute ethanol stress in rats. AB - The plasma arginine vasopressin (AVP), ACTH, and corticosterone levels and the hypothalamic corticotropin-releasing hormone (CRH) content were measured after oral administration of 1 ml of 75% ethanol to rats, a model known to induce acute gastric erosions and stress. Elevated plasma AVP, ACTH, and corticosterone levels were detected 1 h after ethanol administration. Treatment with the vasopressin pressor (V(1)) receptor antagonist [d(CH(2))(5)Tyr(Me)-AVP] before ethanol administration significantly reduced the ACTH and corticosterone level increases. A higher hypothalamic CRH content was measured at 30 or 60 min after ethanol administration. V(1) receptor antagonist injection, 5 min before ethanol administration, inhibited the rise in hypothalamic CRH content. The protein synthesis blocker cycloheximide prevented the hypothalamic CRH content elevation after stress. The AVP-, CRH-, and AVP + CRH-induced in vitro ACTH release in normal anterior pituitary tissue cultures was also prevented by pretreatment with the V(1) receptor antagonist. The results support the hypothesis that stress induced AVP may not only act directly on the ACTH producing anterior pituitary cells but also indirectly at the hypothalamic level via the synthesis and release of CRH. PMID- 11208577 TI - Feeding inhibition by urocortin in the rat hypothalamic paraventricular nucleus. AB - Ventricular administration of urocortin (UCN) inhibits feeding, but specific site(s) of UCN action are unknown. In the current studies we examined the effect of UCN in the hypothalamic paraventricular nucleus (PVN) on feeding. We tested UCN administered into the PVN in several paradigms: deprivation-induced, nocturnal, and neuropeptide Y (NPY)-induced feeding. We compared the effect of equimolar doses of UCN and corticotrophin releasing hormone (CRH) on NPY-induced and nocturnal feeding, determined whether UCN in the PVN produced a conditioned taste aversion (CTA) and induced changes in c-Fos immunoreactivity (c-Fos-ir) after UCN and NPY administration in the PVN. UCN in the PVN significantly decreased NPY and nocturnal and deprivation-induced feeding at doses of 1, 10, and 100 pmol, respectively. UCN anorectic effects lasted longer than those attributed to CRH. Ten and thirty picomoles UCN did not induce a CTA, whereas 100 pmol UCN produced a CTA. UCN (100 pmol) in the PVN neither increased c-Fos-ir in any brain region assayed nor altered c-Fos-ir patterns resulting from PVN NPY administration. These data suggest the hypothalamic PVN as a site of UCN action. PMID- 11208578 TI - Physicochemical analysis of phasic menstrual cycle effects on acid-base balance. AB - In accordance with Stewart's physicochemical approach, the three independent determinants of plasma hydrogen ion concentration ([H(+)]) were measured at rest and during exercise in the follicular (FP) and luteal phase (LP) of the human menstrual cycle. Healthy, physically active women with similar physical characteristics were tested during either the FP (n = 14) or LP (n = 14). Arterialized blood samples were obtained at rest and after 5 min of upright cycling at both 70 and 110% of the ventilatory threshold (T(Vent)). Measurements included plasma [H(+)], arterial carbon dioxide tension (Pa(CO(2))), total weak acid ([A(Tot)]) as reflected by total protein, and the strong-ion difference ([SID]). The transition from rest to exercise in both groups resulted in a significant increase in [H(+)] at 70% T(Vent) versus rest and at 110% T(Vent) versus both rest and 70% T(Vent). No significant between-group differences were observed for [H(+)] at rest or in response to exercise. At rest in the LP, [A(Tot)] and Pa(CO(2)) were significantly lower (acts to decrease [H(+)]) compared with the FP. This effect was offset by a reduction in [SID] (acts to increase [H(+)]). After the transition from rest to exercise, significantly lower [A(Tot)] during the LP was again observed. Although the [SID] and Pa(CO(2)) were not significantly different between groups, trends for changes in these two variables were similar to changes in the resting state. In conclusion, mechanisms regulating [H(+)] exhibit phase-related differences to ensure [H(+)] is relatively constant regardless of progesterone-mediated ventilatory changes during the LP. PMID- 11208579 TI - Relationship of ovarian hormones to hypoxemia in women residents of 4,300 m. AB - Prevalence of excessive erythrocytosis, the main sign of chronic mountain sickness (CMS), is greater in postmenopausal Andean women than in premenopausal women. It is uncertain whether this greater prevalence is related to the decline in female hormones and ventilatory function after the occurrence of the menopause. To study this, we compared the physiological variables involved in the physiopathology of CMS [end-tidal CO(2) (PET(CO(2)), Torr) and end-tidal O(2) (PET(O(2)), Torr), arterial oxygen saturation (Sa(O(2)), %), and Hb concentration (g/dl)] and progesterone and estradiol levels between postmenopausal and premenopausal women, both in the luteal and follicular phases. Women residing in Cerro de Pasco (n = 33; 4,300 m) aged 26--62 yr were studied. Postmenopausal women compared with premenopausal women in the luteal phase had lower PET(O(2)) (48 +/- 4 vs. 53 +/- 2 Torr, P = 0.005) and Sa(O(2)) levels (82 +/- 12 vs. 88 +/- 12%, P < 0.005) and higher PET(CO(2)) (34 +/- 2 vs. 29 +/- 3 Torr, P = 0.005) and Hb concentration (19 +/- 1 vs. 14 +/- 2 g/dl, P < 0.005). In addition, plasma progesterone was negatively correlated with PET(CO(2)) and positively correlated with PET(O(2)) and Sa(O(2)). No clear relationship was found among the cycle phases between estradiol and the variables studied. In conclusion, our results reveal that, before menopause, there is better oxygenation and lower Hb levels in women long residing at altitude, and this is associated with higher levels of progesterone in the luteal phase of the cycle. PMID- 11208580 TI - Caffeine stores and dopamine differentially require Ca(2+) channels in goldfish somatotropes. AB - The regulation of growth hormone (GH) secretion by intracellular Ca(2+) stores was studied in dissociated goldfish somatotropes. We characterized a caffeine activated intracellular store that had been shown to mediate GH release in response to gonadotropin-releasing hormone. The peak response of caffeine stimulation was reduced by approximately 28% by 100 microM ryanodine in a use dependent manner suggesting that the first 10 min of GH release is partially mediated by a caffeine-activated ryanodine receptor. The temporal sensitivities of caffeine- and dopamine-evoked GH release to blockade of Cd(2+)-sensitive Ca(2+) channels were compared. We demonstrated that the initial phase of dopamine evoked release was dependent on Ca(2+) channels, whereas the initial phase of caffeine-evoked release was sensitive only to pretreatment blockade. This would suggest that the maintenance of one class of caffeine-activated intracellular stores requires entry of Ca(2+) through Cd(2+)-sensitive Ca(2+) channels. This differential temporal requirement for Ca(2+) channels in Ca(2+) signaling may be a mechanism to segregate intracellular signaling pathways of multiple neuroendocrine regulators in the teleost pituitary. PMID- 11208581 TI - Acute changes in the response to peripheral leptin with alteration in the diet composition. AB - Dietary induced obesity in rodents is associated with a resistance to leptin. We have investigated the hypothesis that dietary fat per se alters the feeding response to peripheral leptin in rats that were fed either their habitual high- or low-fat diet or were naively exposed to the alternative diet. Osborne-Mendel rats were adapted to either high- or low-fat diet. Food-deprived rats were given either leptin (0.5 mg/kg body wt ip) or saline, after which they were provided with either their familiar diet or the alternative diet. Food intake of rats adapted and tested with the low-fat diet was reduced 4 h after leptin injection, whereas rats adapted and tested with a high-fat diet did not respond to leptin. Leptin was injected again 1 and 5 days after the high-fat diet-adapted rats were switched to the low-fat diet. Leptin reduced the food intake on both days. In contrast, when low-fat diet-adapted rats were switched to a high-fat diet, the leptin inhibitory response was present on day 1 but not observed on day 5. Peripheral injection of leptin increased serum corticosterone level and decreased hypothalamic neuropeptide Y mRNA expression in rats fed the low-fat but not the high-fat diet for 20 days. The data suggest that dietary fat itself, rather than obesity, may induce leptin resistance within a short time of exposure to a high fat diet. PMID- 11208582 TI - Role of PAC(1) receptor in adrenal catecholamine secretion induced by PACAP and VIP in vivo. AB - The present study was conducted to investigate the functional implication of the pituitary adenylate cyclase-activating polypeptide (PACAP) type I (PAC(1)) receptor in the adrenal catecholamine (CA) secretion induced by either PACAP-27 or vasoactive intestinal polypeptide (VIP) in anesthetized dogs. PACAP-27, VIP, and their respective antagonists were locally infused to the left adrenal gland via the left adrenolumbar artery. Plasma CA concentrations in adrenal venous and aortic blood were determined by means of a high-performance liquid chromatograph coupled with an electrochemical detector. Adrenal venous blood flow was measured by gravimetry. The administration of PACAP-27 (50 ng) resulted in a significant increase in adrenal CA output. VIP (5 microg) also increased the basal CA secretion to an extent comparable to that observed with PACAP-27. In the presence of PACAP partial sequence 6--27 [PACAP-(6--27); a PAC(1) receptor antagonist] at the doses of 7.5 and 15 microg, the CA response to PACAP-27 was attenuated by approximately 50 and approximately 95%, respectively. Although the CA secretagogue effect of VIP was blocked by approximately 85% in the presence of PACAP-(6--27) (15 microg), it remained unaffected by VIP partial sequence 10--28 [VIP-(10--28); a VIP receptor antagonist] at the dose of 15 microg. Furthermore, the CA response to PACAP-27 did not change in the presence of the same dose of VIP--(10--28). The results indicate that PACAP-(6--27) diminished, in a dose dependent manner, the increase in adrenal CA secretion induced by PACAP-27. The results also indicate that the CA response to either PACAP-27 or VIP was selectively inhibited by PACAP-(6--27) but not by VIP-(10--28). It is concluded that PAC(1) receptor is primarily involved in the CA secretion induced by both PACAP-27 and VIP in the canine adrenal medulla in vivo. PMID- 11208583 TI - Purine and pyrimidine nucleotide-sensitive phospholipase A(2) in ampulla from frog semicircular canal. AB - This study was attempted to characterize pharmacologically the P2Y receptors triggering phospholipase A(2) (PLA(2)) activation in ampulla from frog semicircular canal. A microassay was developed to screen the abilities of UTP analogs to stimulate [(3)H]arachidonic acid release by labeled ampullas. At 26 degrees C UTP induced a dose-dependent and saturable increase of PLA(2) activity (apparent activation constant 1.3 +/- 0.4 microM, Hill coefficient 0.9 +/- 0.2, maximal stimulating factor 2.0 +/- 0.1). The rank order of potency of agonists for PLA(2) activation was UTP > or = UDP > adenosine 5'-O-(2-thiodiphosphate) = adenosine 5'-O-(3-thiotriphosphate) > or = ATP = 2-methylthio-ATP > or = ADP = diadenosine tetraphosphate > or = alpha,beta-methylene-ATP = CTP > 2' and 3'-O-(4 benzoylbenzoyl)-ATP > or = AMP = UMP >> uridine and adenosine. UTP- and 2 methylthio-ATP-induced PLA(2) activations were inhibited by U-73122, GF-109203X, and methyl arachidonyl fluorophosphate. Basal activity was stimulated by phorbol ester and epinephrine and reduced by vasotocin, isoproterenol, prostaglandin E(2), cAMP, and forskolin. H-89 restored the cAMP- and forskolin-inhibited PLA(2) activities. Results indicate that P2Y receptor-mediated PLA(2) stimulation requires phopholipase C and protein kinase C activations and basal activity is inhibited by agonist-stimulated cAMP-dependent mechanisms. PMID- 11208584 TI - Effects of 17 beta-estradiol on levels and distribution of metallothionein and zinc in squirrelfish. AB - Females of the squirrelfish family (Holocentridae) accumulate higher levels of zinc in the liver than any other known animal. This zinc accumulation is made possible by high expression of the zinc-binding protein, metallothionein (MT). In the present study, the squirrelfish (Holocentrus ascensionis) MT cDNA was cloned and sequenced. The deduced amino acid sequence was very similar to other teleost MT. The role of estrogens on zinc metabolism was investigated by injecting male and immature female squirrelfish with 17 beta-estradiol (E(2)). E(2) treatment triggered transient increases in plasma zinc and vitellogenin (VTG) levels, and both of these variables showed very similar time courses. These results suggest that E(2) is responsible for the large hepatoovarian translocation of zinc observed in female squirrelfish and that VTG might be a vehicle for zinc. E(2) did not directly alter the levels of zinc or MT mRNA in the liver. However, the hepatic MT protein concentration increased differentially in the nuclear fraction. Thus E(2) is probably responsible for the association of MT with the nuclear fraction previously observed in untreated mature female squirrelfish. PMID- 11208585 TI - Role of inferior olive and thoracic IML neurons in nonshivering thermogenesis in rats. AB - Removal of the midbrain tonic inhibitory mechanism on nonshivering thermogenesis (NST) results in increased temperatures of the interscapular brown adipose tissue (IBAT) and rectum (T(IBAT) and T(rec), respectively) via an enhanced central sympathetic output. Because it is unlikely that neurons (primary) of the midbrain inhibitory mechanism tonically inhibit the IBAT monosynaptically, there must be secondary or tertiary neurons posterior to the midbrain. Such neurons, therefore, may increase their activity during enhanced NST after removal of the midbrain tonic inhibition. The aim of the present experiments was to localize these secondary or tertiary neurons and establish descending neuronal pathway(s) that may project to the major NST effector IBAT. T(IBAT) and T(rec) increases induced by removal of the tonic inhibition by midbrain procaine microinjections were accompanied with appearance of c-Fos-positive neurons in the inferior olive (IO) and the intermediolateral (IML) cell column of the thoracic spinal cord. Electrical stimulation of and L-glutamate microinjections into the IO increased T(IBAT) and T(rec). Midbrain procaine-induced T(IBAT) and T(rec) increases were blocked by electrolytic IO lesions. These results suggest that central thermal signals produced from the lower midbrain are transmitted to IBAT through the IO and IML and that the IO has a role in the central sympathetic functions. PMID- 11208586 TI - Effects of postnatal dexamethasone on blood-brain barrier permeability and brain water content in newborn lambs. AB - We showed that antenatal corticosteroids reduced blood-brain barrier permeability in fetuses at 60 and 80%, but not 90% of gestation, and decreased brain water content in fetuses. Our objective was to examine the effects of postnatal corticosteroids on regional blood-brain barrier permeability and brain water content in newborn lambs. Three dexamethasone treatment groups were studied in 3- to 5-day-old lambs. A 0.01 mg/kg dose was selected to estimate the amount of dexamethasone that might have reached fetuses via antenatal treatment of ewes in our previous studies. The other doses (0.25 and 0.5 mg/kg) were chosen to approximate those used clinically to treat infants with bronchopulmonary dysplasia. Lambs were randomly assigned to receive four intramuscular injections of dexamethasone or placebo given 12 h apart on days 3 and 4 of age. Blood-brain barrier function was measured with the blood-to-brain transfer constant (K(i)) to alpha-aminoisobutyric acid, brain plasma volume was measured with polyethylene glycol for the calculation of K(i,) and brain water was measured by wet-to-dry tissue weights. Postnatal treatment with corticosteroids did not reduce barrier permeability in newborn lambs. Brain blood volume was higher in the 0.25 and 0.5 mg/kg dose dexamethasone groups than in the placebo group. Brain water content did not differ among the groups. We conclude that postnatal treatment with corticosteroids did not reduce regional blood-brain barrier permeability or brain water content but increased the brain plasma volume in newborn lambs. These findings are consistent with our previous work indicating that barrier permeability is responsive to corticosteroids at 60 and 80% of gestation and brain water regulation at 60% of gestation, but not in near-term fetuses or newborn lambs. PMID- 11208587 TI - Development of fetal vascular responses to endothelin-1 and acetylcholine in the sheep. AB - Responses to K(+), endothelin-1 (ET-1), and acetylcholine (ACh) of isolated adrenal, femoral, middle cerebral, and renal arteries from fetal [110--145 days gestational age (dGA, term approximately 148 dGA)] and 0- to 24-h newborn (NB) lambs were evaluated using the technique of wire myography. Responses at distinct developmental ages for each vascular bed were compared. In all arteries sensitivity to K(+)-induced vasoconstriction was similar at all fetal age points examined. In contrast, sensitivity to ET-1 increased with increasing fetal age in arteries from all vascular beds. The magnitude of the maximal vasoconstriction was positively correlated with GA for K(+) in adrenal, femoral, and cerebral arteries and for ET-1 in femoral, cerebral, and renal arteries. Cerebral arteries showed a greater sensitivity when compared with the other systemic arteries to K(+) and ET-1 at all fetal ages and to K(+) in NB. ACh evoked relaxatory responses in fetal and NB femoral and adrenal arteries. However, renal arteries relaxed comparatively less in response to ACh, and no vasodilation was noted in middle cerebral arteries at any age points examined. For femoral arteries ACh induced vasorelaxation decreased with increasing GA but was restored in arteries from NB lambs. In summary, the responsiveness of isolated resistance arteries varies with developmental age in the fetal and perinatal sheep and these effects are both agonist and vascular bed specific. The augmented sensitivity in response to ET-1 of middle cerebral compared with other systemic arteries may reflect the importance of cerebral blood flow control during this critical developmental period. PMID- 11208588 TI - Noradrenergic and GABAergic systems in the medial hypothalamus are activated during hypoglycemia. AB - Noradrenergic and GABAergic systems in the medial hypothalamus influence plasma glucose and may be activated during glucoprivation. Microdialysis probes were placed into the ventromedial nucleus (VMH), lateral hypothalamus (LHA), and paraventricular nucleus (PVH) of male Sprague-Dawley rats to monitor extracellular concentrations of norepinephrine (NE) and GABA. During systemic hypoglycemia, induced by insulin (1.0 U/kg), NE concentrations increased in the VMH (P < 0.05) and PVH (P = 0.06) in a bimodal fashion during the first 10 min and 20-30 min after insulin administration. In the VMH, GABA concentrations increased (P < 0.05) in a similar manner as NE. Extracellular NE concentrations in the LHA were slightly lower (P = 0.13), and GABA levels remained at baseline. The increases in NE and GABA in the VMH were absent during euglycemic clamp; however, NE in the PVH still increased, reflecting a direct response to hyperinsulinemia. On the basis of these data, we propose that the activity of noradrenergic afferents to the medial hypothalamus is increased during hypoglycemia and influences the activity of local GABAergic systems to activate appropriate physiological compensatory mechanisms. PMID- 11208589 TI - Effects of glucose supplementation on gastric emptying, blood glucose homeostasis, and appetite in the elderly. AB - The aims of this study were to evaluate the effects of dietary glucose supplementation on gastric emptying (GE) of both glucose and fat, postprandial blood glucose homeostasis, and appetite in eight older subjects (4 males, 4 females, aged 65--84 yr). GE of a drink (15 ml olive oil and 33 g glucose dissolved in 185 ml water), blood glucose, insulin, gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), and appetite (diet diaries, visual analog scales, and food intake at a buffet meal consumed after the GE study) were evaluated twice, after 10 days on a standard or a glucose supplemented diet (70 g glucose 3 times a day). Glucose supplementation accelerated GE of glucose (P < 0.05), but not oil; there was a trend for an increase in GIP (at 15 min, P = 0.06), no change in GLP-1, an earlier insulin peak (P < 0.01), and a subsequent reduction in blood glucose (at 75 min, P < 0.01). Glucose supplementation had no effect on food intake during each diet so that energy intake was greater (P < 0.001) during the glucose-supplemented diet. Appetite ratings and energy intake at the buffet meal were not different. We conclude that, in older subjects, glucose supplementation 1) accelerates GE of glucose, but not fat; 2) modifies postprandial blood glucose homeostasis; and 3) increases energy intake. PMID- 11208590 TI - Influence of rostral ventrolateral medulla on renal sympathetic baroreflex in conscious rabbits. AB - Previous studies with anesthetized animals have shown that the pressor region of the rostral ventrolateral medulla (RVLM) is a critical site in vasomotor control. The aim of this study was to develop, in conscious rabbits, a technique for microinjecting into the RVLM and to determine the influence of this area on renal sympathetic nerve activity (RSNA) and arterial pressure (AP) using local injections of glutamate, rilmenidine, ANG II and sarile. Rabbits were implanted with guide cannulas for bilateral microinjections into the RVLM (n = 7) or into the intermediate ventrolateral medulla (IVLM, n = 6) and an electrode for measuring RSNA. After 7 days of recovery, injections of glutamate (10 and 20 nmol) into the RVLM increased RSNA by 81 and 88% and AP by 17 and 25 mmHg, respectively. Infusion of glutamate (2 nmol/min) into the RVLM increased AP by 15 mmHg and the RSNA baroreflex range by 38%. By contrast, injection of the imidazoline receptor agonist rilmenidine (4 nmol) into the RVLM decreased AP by 8 mmHg and the RSNA baroreflex range by 37%. Injections of rilmenidine into the IVLM did not alter AP or RSNA. Surprisingly, treatments with ANG II (4 pmol/min) or the ANG II receptor antagonist sarile (500 pmol) into the RVLM did not affect the resting or baroreflex parameters. Infusion of ANG II (4 pmol/min) into the fourth ventricle increased AP and facilitated the RSNA baroreflex. Our results show that agents administered via a novel microinjecting system for conscious rabbits can selectively modulate neuronal activity in circumscribed regions of the ventrolateral medulla. We conclude that the RVLM plays a key role in circulatory control in conscious rabbits. However, we find no evidence for the role of ANG II receptors in the RVLM in the moment-to-moment regulation of AP and RSNA. PMID- 11208591 TI - Modeling the kinematics of the canine midcostal diaphragm. AB - The hypotheses that the chest wall insertion (CW) is displaced laterally during inspiration and that this displacement is essential in maintaining muscle curvature of the costal diaphragmatic muscle fibers were tested. With the use of data from three dogs, caudal, lateral, and ventral displacements of CW during both quiet, spontaneous inspiration and during inspiratory efforts against an occluded airway were observed and recorded. We have developed a kinematic model of the diaphragm that incorporates these displacements. This model describes the motions of the muscle fibers and central tendon; the displacements of the midplane, muscle-tendon junction (MTJ), CW, and center of the muscle fiber central tendon arcs are modeled as functions of muscle fiber length. In the model, the center of the fiber arcs and MTJ both move caudally parallel to the midplane during inspiration, whereas CW moves both caudally and laterally. The observed lateral displacement of CW and the observed caudal displacement of MTJ, as functions of muscle fiber length, both approximate well the theoretical displacements that would be necessary to maintain curvature of the fiber arcs. In confirming our hypotheses, we have found that lateral displacement of CW is a mechanism by which changes in the shape of the costal diaphragm, as described by its curvature, are limited. PMID- 11208592 TI - Basal forebrain acetylcholine release during REM sleep is significantly greater than during waking. AB - Cholinergic neurons of the basal forebrain supply the neocortex with ACh and play a major role in regulating behavioral arousal and cortical electroencephalographic activation. Cortical ACh release is greatest during waking and rapid eye movement (REM) sleep and reduced during non-REM (NREM) sleep. Loss of basal forebrain cholinergic neurons contributes to sleep disruption and to the cognitive deficits of many neurological disorders. ACh release within the basal forebrain previously has not been quantified during sleep. This study used in vivo microdialysis to test the hypothesis that basal forebrain ACh release varies as a function of sleep and waking. Cats were trained to sleep in a head-stable position, and dialysis samples were collected during polygraphically defined states of waking, NREM sleep, and REM sleep. Results from 22 experiments in four animals demonstrated that means +/- SE ACh release (pmol/10 min) was greatest during REM sleep (0.77 +/- 0.07), intermediate during waking (0.58 +/- 0.03), and lowest during NREM sleep (0.34 +/- 0.01). The finding that, during REM sleep, basal forebrain ACh release is significantly elevated over waking levels suggests a differential role for basal forebrain ACh during REM sleep and waking. PMID- 11208593 TI - Multiple aspects of mineralocorticoid selectivity. AB - Aldosterone regulates renal sodium reabsorption through binding to the mineralocorticoid receptor (MR). Because the glucocorticoid receptor (GR) is expressed together with the MR in aldosterone target cells, glucocorticoid hormones bound to GR may also intervene to modulate physiological functions in these cells. In addition, each steroid can bind both receptors, and the MR has equal affinity for aldosterone and glucocorticoid hormones. Several cellular and molecular mechanisms intervene to allow specific aldosterone regulatory effects, despite the large prevalence of glucocorticoid hormones in the plasma. They include the local metabolism of the glucocorticoid hormones into inactive derivatives by the enzyme 11beta-hydroxysteroid dehydrogenase; the intrinsic properties of the MR that discriminate between ligands through differential contacts; the possibility of forming homo- or heterodimers between MR and GR, leading to differential transactivation properties; and the interactions of MR and GR with other regulatory transcription factors. The relative contribution of each of these successive mechanisms may vary among aldosterone target cells (epithelial vs. nonepithelial) and according to the hormonal context. All these phenomena allow fine tuning of cellular functions depending on the degree of cooperation between corticosteroid hormones and other factors (hormonal or tissue specific). Such interactions may be altered in pathophysiological situations. PMID- 11208594 TI - Cellular regulation of endothelial nitric oxide synthase. AB - Renal function is highly dependent on endothelium-derived nitric oxide (NO). Several renal disorders have been linked to impaired NO bioavailability. The enzyme that is responsible for the synthesis of NO within the renal endothelium is endothelial NO synthase (eNOS). eNOS-mediated NO generation is a highly regulated cellular event, which is induced by calcium-mobilizing agonists and fluid shear stress. eNOS activity is regulated at the transcriptional level but also by a variety of modifications, such as acylation and phosphorylation, by its cellular localization, and by protein-protein interactions. The present review focuses on the complex regulation of eNOS within the endothelial cell. PMID- 11208595 TI - Renal effects of serine-7 analog of lymphoguanylin in ex vivo rat kidney. AB - Guanylin and uroguanylin compose a family of natriuretic, diuretic, and kaliuretic peptides that bind to and activate apical membrane receptor guanylyl cyclase signaling molecules in renal and intestinal epithelia. Recently, a complementary DNA encoding an additional member of the guanylin family of cGMP regulating peptides was isolated from lymphoid tissues of the opossum and was termed lymphoguanylin (LGN). A peptide analog of opossum LGN was synthesized containing a single disulfide bond with the internal cysteine-7 replaced by a serine residue (LGN(Cys7-->Ser7)). The biological activity of LGN(Ser) was tested by using a cGMP bioassay with cultured T84 (human intestinal) cells and opossum kidney (OK) cells. LGN(Ser) has potencies and efficacies for activation of cGMP production in the intestinal and kidney cell lines that are 100- and 1,000-fold higher than LGN, respectively. In the isolated perfused rat kidney, LGN(Ser) stimulated a maximal increase in fractional Na+ excretion from 24.8 +/- 3.0 to 36.3 +/- 3.3% 60 min after administration and enhanced urine flow from 0.15 +/- 0.01 to 0.24 +/- 0.01 ml. g(-1). min(-1). LGN(Ser) (0.69 microM) also increased fractional K+ excretion from 27.3 +/- 2.3 to 38.0 +/- 3.0% and fractional Cl- excretion from 26.1 +/- 0.8 to 43.5 +/- 1.9. A ninefold increase in the urinary excretion of cGMP from 1.00 +/- 0.04 to 9.28 +/- 1.14 pmol/ml was elicited by LGN(Ser), whereas cAMP levels were not changed on peptide administration. These findings demonstrate that LGN(Ser), which contains a single disulfide bond like native LGN, activates guanylyl cyclase-C (GC-C) receptors in T84 and OK cells and may be very helpful in studying the physiological importance of activation of GC C in vivo. LGN(Ser) also exhibits full activity in the isolated perfused kidney equivalent to that observed previously with opossum uroguanylin, suggesting a physiological role for LGN in renal function. Thus the single amino acid substitution enhances the activity and potency of LGN. PMID- 11208596 TI - Location and function of the epithelial Na channel in the cochlea. AB - In the cochlea, endolymph is a K-rich and Na-poor fluid. The purpose of the present study was to check the presence and to assess the role of epithelial Na channel (ENaC) in this organ. alpha-, beta-, and gamma-ENaC subunit mRNA, and proteins were detected in rat cochlea by RT-PCR and Western blot. alpha-ENaC subunit mRNA was localized by in situ hybridization in both epithelial (stria vascularis, spiral prominence, spiral limbus) and nonepithelial structures (spiral ligament, spiral ganglion). The alpha-ENaC-positive tissues were also positive for beta-subunit mRNA (except spiral ganglion) or for gamma-subunit mRNA (spiral limbus, spiral ligament, and spiral ganglion), but the signals of beta- and gamma-subunits were weaker than those observed for alpha-subunit. In vivo, the endocochlear potential was recorded in guinea pigs under normoxic and hypoxic conditions after endolymphatic perfusion of ENaC inhibitors (amiloride, benzamil) dissolved either in K-rich or Na-rich solutions. ENaC inhibitors altered the endocochlear potential when Na-rich but not when K-rich solutions were perfused. In conclusion, ENaC subunits are expressed in epithelial and nonepithelial cochlear structures. One of its functions is probably to maintain the low concentration of Na in endolymph. PMID- 11208597 TI - Role of 20-HETE in mediating the effect of dietary K intake on the apical K channels in the mTAL. AB - We have used the patch-clamp technique to study the effect of dietary K intake on the apical K channels in the medullary thick ascending limb (mTAL) of rat kidneys. The channel activity, defined by the number of channels in a patch and the open probability (NPo), of the 30- and 70-pS K channels, was 0.18 and 0.11, respectively, in the mTAL from rats on a K-deficient diet. In contrast, NPo of the 30- and 70-pS K channels increased to 0.60 and 0.80, respectively, in the tubules from animals on a high-K diet. The concentration of 20 hydroxyeicosatetraenoic acid (20-HETE) measured with gas chromatography-mass spectrometry was 0.8 pg/microg protein in the mTAL from rats on a high-K diet and increased significantly to 4.6 pg/microg protein in the tubules from rats on a K deficient diet. Addition of N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS) or 17-octadecynoic acid (17-ODYA), agents that inhibit the formation of 20-HETE, had no significant effect on the activity of the 30-pS K channels. However, DDMS/17-ODYA significantly increased the activity of the apical 70-pS K channel from 0.11 to 0.91 in the mTAL from rats on a K-deficient diet. In contrast, inhibition of the cytochrome P-450 metabolism of arachidonic acid increased NPo from 0.64 to 0.81 in the tubules from animals on a high-K diet. Furthermore, the sensitivity of the 70-pS K channel to 20-HETE was the same between rats on a high K diet and on a K-deficient diet. Finally, the pretreatment of the tubules with DDMS increased NPo of the 70-pS K channels in the mTAL from rats on a K-deficient diet to 0.76. We conclude that an increase in 20-HETE production is involved in reducing the activity of the apical 70-pS K channels in the mTAL from rats on a K deficient diet. PMID- 11208598 TI - Renal interstitial adenosine metabolism during ischemia in dogs. AB - The present study was conducted to determine the metabolism of renal interstitial adenosine under resting conditions and during ischemia. By using a microdialysis method with HPLC-fluorometric analysis, renal interstitial concentrations of adenosine, inosine, and hypoxanthine were assessed in pentobarbital-anesthetized dogs. Average basal renal interstitial concentrations of adenosine, inosine, and hypoxanthine were 0.18 +/- 0.04, 0.31 +/- 0.05, and 0.35 +/- 0.05 micromol/l, respectively. Local inhibition of adenosine kinase with iodotubercidin (10 micromol/l in perfusate) or inhibition of adenosine deaminase with erythro-9-(2 hydroxy-3-nonyl)adenine (EHNA; 100 micromol/l in perfusate) did not change adenosine concentrations in the nonischemic kidneys (0.18 +/- 0.04 and 0.24 +/- 0.05 micromol/l, respectively). On the other hand, treatment with iodotubercidin+EHNA significantly increased adenosine concentration (0.52 +/- 0.07 micromol/l) with significant decreases in inosine and hypoxanthine levels (0.13 +/- 0.03 and 0.19 +/- 0.04 micromol/l, respectively). During 30 min of ischemia, adenosine, inosine, and hypoxanthine were significantly increased to 0.76 +/- 0.29, 2.14 +/- 0.45, and 21.8 +/- 4.7 micromol/l, respectively. The treatment with iodotubercidin did not alter ischemia-induced increase in adenosine (0.84 +/- 0.18 micromol/l); however, EHNA alone markedly enhanced adenosine accumulation (13.54 +/- 2.16 micromol/l), the value of which was not augmented by an addition of iodotubercidin (15.80 +/- 1.24 micromol/l). In contrast, ischemia-induced increases in inosine and hypoxanthine were inversely diminished by the treatment with iodotubercidin+EHNA (0.90 +/- 0.20 and 9.86 +/- 1.96 micromol/l, respectively). These results suggest that both adenosine kinase and adenosine deaminase contribute to the metabolism of renal interstitial adenosine under resting conditions, whereas adenosine produced during ischemia is mainly metabolized by adenosine deaminase and the rephosphorylation of adenosine by adenosine kinase is small.sent PMID- 11208599 TI - Peritubular fluid viscosity modulates H+ flux in proximal tubules through NO release. AB - We evaluated the effects of increasing the viscosity (eta) in peritubular capillary perfusates (PCP; 20 mM HNaPO4--Ringer, pH 7.4) on proximal convoluted tubule (PCT) acidification. Micropuncture experiments were performed with simultaneous luminal and peritubular perfusion. Changes in pH of a 20 mM HNaPO4- Ringer (pH 7.4 at t = 0) droplet placed in PCT lumen were measured with H+ sensitive microelectrodes. By adding neutral dextran (molecular wt 300,000 400,000) to the PCP, eta was increased. The effect of 10(-5) M ATP added to normal-eta PCP was evaluated. High eta increased H+ flux (85 and 97% when eta was increased 20 and 30%, respectively, above the control value). This increase was abolished by adding the nitric oxide antagonist N(omega)-nitro-L-arginine (L-NNA; 10(-4) M) or the purinoreceptor antagonists suramin (10(-4) M) and reactive blue 2 (3 x 10(-5) M). Addition of 5 x 10(-3) M L-arginine to the peritubular perfusate overcame the inhibitory effect of L-NNA on high-eta-induced increase in H+ flux. ATP increased H+ flux (80%), and this effect was blocked by L-NNA. These results suggest that changes in eta can modulate proximal H+ flux, at least in part, through ATP-dependent nitric oxide release from the endothelial cells of the peritubular capillaries. PMID- 11208600 TI - An endocytosis defect as a possible cause of proteinuria in polycystic kidney disease. AB - Because proteinuria has been demonstrated in patients with autosomal-dominant polycystic kidney disease (ADPKD), we have investigated whether proteinuria also occurs in the (cy/+) rat, a widely used model for ADPKD. Increased urinary excretion of proteins, in particular of albumin, can be found in 16-wk-old (cy/+) rats, with a gel electrophoresis pattern compatible with a tubular origin of proteinuria. Using FITC-labeled dextran as an in vivo tracer for renal tubular endosomal function, we could show that portions of cyst-lining epithelia from proximal tubules have lost the ability to endocytose, which is necessary for the reabsorption of low-molecular-weight proteins. By immunohistochemistry, the expression of other proteins implicated in endocytosis, such as the chloride channel ClC-5 and the albumin receptor megalin, correlated well with the presence and absence of FITC-dextran in cysts. As an example of growth factor systems possibly being affected by this endocytosis defect, we could detect increased urinary levels of insulin-like growth factor-I protein in (cy/+) animals. These data indicate that proteinuria and albuminuria in the aforementioned rat model for ADPKD are due to a loss of the endocytic machinery in epithelia of proximal tubular cysts. This may also affect the concentration of different growth factors and hormones in cyst fluids and thus modulate cyst development. PMID- 11208601 TI - Early streptozotocin-diabetes mellitus downregulates rat kidney AT2 receptors. AB - The interaction of ANG II with intrarenal AT1 receptors has been implicated in the progression of diabetic nephropathy, but the role of intrarenal AT2 receptors is unknown. The present studies determined the effect of early diabetes on components of the glomerular renin-angiotensin system and on expression of kidney AT2 receptors. Three groups of rats were studied after 2 wk: 1) control (C), 2) streptozotocin (STZ)-induced diabetic (D), and 3) STZ-induced diabetic with insulin implant (D+I), to maintain normoglycemia. By competitive RT-PCR, early diabetes had no significant effect on glomerular mRNA expression for renin, angiotensinogen, or angiotensin-converting enzyme (ACE). In isolated glomeruli, nonglycosylated (41-kDa) AT1 receptor protein expression (AT1A and AT1B) was increased in D rats, with no change in glycosylated (53-kDa) AT1 receptor protein or in AT1 receptor mRNA. By contrast, STZ diabetes caused a significant decrease in glomerular AT2 receptor protein expression (47.0 +/- 6.5% of C; P < 0.001; n = 6), with partial reversal in D+I rats. In normal rat kidney, AT2 receptor immunostaining was localized to glomerular endothelial cells and tubular epithelial cells in the cortex, interstitial, and tubular cells in the outer medulla, and inner medullary collecting duct cells. STZ diabetes caused a significant decrease in AT2 receptor immunostaining in all kidney regions, an effect partially reversed in D+I rats. In summary, early diabetes has no effect on glomerular mRNA expression for renin, angiotensinogen, or ACE. AT2 receptors are present in glomeruli and are downregulated in early diabetes, as are all kidney AT2 receptors. Our data suggest that alterations in the balance of kidney AT1 and AT2 receptor expression may contribute to ANG II-mediated glomerular injury in progressive diabetic nephropathy. PMID- 11208602 TI - Molecular and biochemical characterization of prostacyclin receptors in rat kidney. AB - The prostacyclin (IP) message was detected by RT-PCR in the renal cortex, outer (OM) and inner medulla (IM), and in freshly isolated (IMCD-f) and cultured inner medullary collecting duct (IMCD-c), and also the E-prostanoid (EP)1,3,4 receptor subtypes, but not EP2. Digoxigenin in situ hybridization localized IP mRNA in the tubules of the OM and IM, and the vasculature, and also in the glomeruli, arteries, and tubules of the cortex. IP splice variants or subtypes could not be detected by RT-PCR followed by TA cloning, though several nonfunctional point mutations or single base pair deletions were observed. Iloprost (ILP), cicaprost (CCP), PGE2, and arginine vasopressin (AVP) stimulated cAMP in both IMCD preparations. In addition, AVP-stimulated cAMP in IMCD-f was inhibited by all three prostanoids, but not in IMCD-c. Calcium experiments were performed on IMCD c or microdissected IMCD (IMCD-m). CCP, ILP, and PGE2 did not alter intracellular calcium concentration ([Ca2+]i) in IMCD-c. However, on IMCD-m, both PGE2 and ILP increased [Ca2+]i levels equipotently and CCP had no effect. Pretreatment with the EP1 antagonist AH-6809 indicates that the response to ILP and PGE2 is mediated via EP1. These results suggest that IP receptors in the rat IMCD mediate the cAMP but not calcium signaling linked to PGI2; to date no subtypes or splice variants have been identified. PMID- 11208603 TI - Na+-to-sugar stoichiometry of SGLT3. AB - Sodium-glucose cotransporters (SGLTs) mediate active transport of sugar across cell membranes coupled to Na+, by using the electrochemical gradient as a driving force. In the kidney, there is evidence for two kinds of cotransporters, a high affinity, low-capacity system, and a low-affinity, high-capacity system, with differences in substrate specificity and kinetics. Three renal SGLT clones have been identified: SGLT1 corresponding to the high-affinity system, and SGLT2 and SGLT3 with properties reminiscent of the low-affinity system. We have determined the stoichiometry of pig SGLT3 (pSGLT3) by using a direct method, comparing the substrate-induced inward charge to 22Na or [14C]alpha-methyl-D-glucopyranoside uptake in the same oocyte. pSGLT3 stoichiometry is 2 Na+:1 sugar, the same as that for SGLT1, but different from SGLT2 (1:1). The Na+ Hill coefficient for SGLT3 is approximately 1.5, suggesting low cooperativity between Na+ binding sites. Thus SGLT3 has functional characteristics intermediate between SGLT1 and SGLT2, so, whereas SGLT3 stoichiometry is the same as that for SGLT1 (2:1), sugar affinity and specificity are similar to SGLT2. PMID- 11208604 TI - NHE3 activity and trafficking depend on the state of actin organization in proximal tubule. AB - The present study was addressed to define the contribution of cytoskeleton elements in the kidney proximal tubule Na+/H+ exchanger 3 (NHE3) activity under basal conditions. We used luminal membrane vesicles (LMV) isolated from suspensions of rat cortical tubules pretreated with either colchicine (Colch) or cytochalasin D (Cyto D). Colch pretreatment of suspensions (200 microM for 60 min) moderately decreased LMV NHE3 activity. Cyto D pretreatment (1 microM for 60 min) elicited an increase in LMV NHE3 transport activity but did not increase Na glucose cotransport activity. Cyto D pretreatment of suspensions did not change the apparent affinity of NHE3 for internal H+. In contrast, after Cyto D pretreatment of the suspensions, NHE3 protein abundance was increased in LMV and remained unchanged in cortical cell homogenates. The effect of Cyto D on NHE3 was further assessed with cultures of murine cortical cells. The amount of surface biotinylated NHE3 increased on Cyto D treatment, whereas NHE3 protein abundance was unchanged in cell homogenates. In conclusion, under basal conditions NHE3 activity depends on the state of actin organization possibly involved in trafficking processes between luminal membrane and intracellular compartment. PMID- 11208606 TI - SGK integrates insulin and mineralocorticoid regulation of epithelial sodium transport. AB - The epithelial Na+ channel (ENaC) constitutes the rate-limiting step for Na+ transport across tight epithelia and is the principal target of hormonal regulation, particularly by insulin and mineralocorticoids. Recently, the serine threonine kinase (SGK) was identified as a rapidly mineralocorticoid-responsive gene, the product of which stimulates ENaC-mediated Na+ transport. Like its close relative, protein kinase B (also called Akt), SGK's kinase activity is dependent on phosphatidylinositol 3-kinase (PI3K), a key mediator of insulin signaling. In our study we show that PI3K is required for SGK-dependent stimulation of ENaC mediated Na+ transport as well as for the production of the phosphorylated form of SGK. In A6 kidney cells, mineralocorticoid induction of the phosphorylated form of SGK preceded the increase in Na+ transport, and specific inhibition of PI3K inhibited both phosphorylation of SGK and mineralocorticoid-induced Na+ transport. Insulin both augmented SGK phosphorylation and synergized with mineralocorticoids in stimulating Na+ transport. In a Xenopus laevis oocyte coexpression assay, SGK-stimulated ENaC activity was also markedly reduced by PI3K inhibition. Finally, in vitro-translated SGK specifically interacted with the ENaC subunits expressed in Escherichia coli as glutathione S-transferase fusion proteins. These data suggest that SGK is a PI3K-dependent integrator of insulin and mineralocorticoid actions that interacts with ENaC subunits to control Na+ entry into kidney collecting duct cells. PMID- 11208605 TI - Regulation of MAP kinase by calcium-sensing receptor in bovine parathyroid and CaR-transfected HEK293 cells. AB - Regulation of the extracellular signal-regulated kinase 1 and 2 (ERK1/2) pathway by the extracellular calcium (Ca2+o)-sensing receptor (CaR) was investigated in bovine parathyroid and CaR-transfected human embryonic kidney (HEKCaR) cells. Elevating Ca2+o or adding the selective CaR activator NPS R-467 elicited rapid, dose-dependent phosphorylation of ERK1/2. These phosphorylations were attenuated by pretreatment with pertussis toxin (PTX) or by treatment with the phosphotyrosine kinase (PTK) inhibitors genistein and herbimycin, the phosphatidylinositol-specific phospholipase C (PI-PLC) inhibitor U-73122, or the protein kinase C (PKC) inhibitor GF109203X and were enhanced by the PKC activator phorbol 12-myristate 13-acetate. Combined treatment with PTX and inhibitors of both PKC and PTK nearly abolished high Ca2+o-evoked ERK1/2 activation in HEKCaR cells, demonstrating CaR-mediated coupling via both Gq and G(i). High Ca2+o increased serine phosphorylation of the 85-kDa cytosolic phospholipase A2 (cPLA2) in both parathyroid and HEKCaR cells. The selective mitogen-activated protein kinase (MAPK) inhibitor PD98059 abolished high-Ca2+o)-induced ERK1/2 activation and reduced cPLA2 phosphorylation in both cell types, documenting MAPK's role in cPLA2 activation. Thus our data suggest that the CaR activates MAPK through PKC, presumably through Gq/11-mediated activation of PI-PLC, as well as through G(i)- and PTK-dependent pathway(s) in bovine parathyroid and HEKCaR cells and indicate the importance of MAPK in cPLA2 activation. PMID- 11208607 TI - Mechanisms of chloride transport in thymic lymphocytes. AB - This study examined mechanisms of Cl- transport in rat lymphocytes under a variety of conditions. Basal intracellular Cl- concentration ([Cl-]i) was not different between cells assayed in the presence of HCO3- or its absence (HEPES). Removal of external Cl- resulted in a fall in [Cl-]i and a rapid rise in intracellular pH (pH(i)). Both Cl- efflux and the rise in pH(i) were blocked by DIDS or removal of external Na+ but were unaffected by furosemide. The mechanisms governing Cl- influx were assessed in cells that had been Cl- depleted for 1 h. Reexposure to Cl- resulted in a rapid rise in [Cl-]i that was partially inhibited by pretreatment with DIDS (57%) and partially inhibited by pretreatment with furosemide (45%). Pretreatment with both compounds together completely blocked Cl influx. Cl- depletion caused a marked increase in pH(i) that rapidly declined toward normal when the cells were reexposed to Cl-. Preincubation with DIDS completely blocked this decrease in pH(i). In contrast, neither removal of Na+ nor preincubation with furosemide affected the decline in pH(i) when the cells were reexposed to Cl-. We conclude that, in thymic lymphocytes, Cl-/HCO3- (or Cl /base exchange) regulates both Cl- influx and efflux. Cl- efflux is totally inhibited by DIDS and is mediated by a Na+-dependent Cl-/HCO3- exchanger. Cl- influx is partially DIDS sensitive and partially furosemide sensitive and is mediated by both a Na+-independent Cl-/HCO3- exchanger and by a Na+-K+-2Cl- cotransporter. PMID- 11208608 TI - UT-A3: localization and characterization of an additional urea transporter isoform in the IMCD. AB - UT-A3 has recently been identified as a splicing variant transcript of the UT-A gene present in the kidney. To study the cellular and subcellular localization of UT-A3, we raised a new polyclonal antibody to its COOH-terminal end. Immunoblots identified bands at 44 and 67 kDa predominately in the inner medulla and showed that the antibody does not recognize UT-A1. Deglycosylation with PNGase decreased the molecular mass of both forms to 40 kDa. UT-A3 is most abundant in the inner third of the inner medulla and is present in membrane fractions. Cell fractionation studies showed that UT-A3 is only detectable in inner medullary collecting duct (IMCD) cells. These observations were confirmed with immunolocalization studies demonstrating an exclusive labeling of IMCD cells. Double-labeling studies with anti-Na-K-ATPase demonstrated UT-A3 in intracellular membranes and in the apical region but were incompatible with a basolateral site for UT-A3. Although the function of this isoform in the inner medulla is unknown, the large abundance suggests that it may be important in the renal handling of urea. PMID- 11208609 TI - Role of 14-3-3epsilon, c-Myc/Max, and Akt phosphorylation in HIV-1 gp 120-induced mesangial cell proliferation. AB - Focal glomerulosclerosis (FGS) is the predominant glomerular lesion in patients with human immunodeficiency virus (HIV)-associated nephropathy. Initial mesangial cell hyperplasia and subsequent hypoplasia are common features of FGS. In the present study we evaluated the effect of HIV-1 glycoprotein (gp) 120 on human mesangial cell (HMC) growth. HIV-1 gp 120 stimulated HMC proliferation at lower concentrations, whereas it suppressed cell proliferation at higher concentrations. In parallel to the modulation of cell growth, gp 120 at low concentrations resulted in an increase in the expression of c-Myc, Max, and 14-3 3epsilon proteins and phosphorylation of ATP-dependent tyrosine kinases (Akt) at Ser(473). However, the expression of these proteins decreased with increasing concentrations of gp 120. Furthermore, gp 120 also exhibited a dose-dependent inhibition of Akt phosphorylation at Ser-473 without any significant alteration of Akt expression. Little or no effects of gp 120 were observed on the expression of extracellular signal-regulated kinase (ERK), phospho-ERK, Bcl-2, and Bax proteins. At a higher concentration, gp 120 not only promoted HMC apoptosis but also enhanced expression of Fas and FasL. These results suggest that HIV-1 gp 120 induces alterations in conflicting survival signaling pathways that contribute to the potential dual effects of gp 120 in promoting or inhibiting HMC proliferation. PMID- 11208610 TI - Mechanisms underlying renoprotection during renin-angiotensin system blockade. AB - Potential determinants of chronic renal disease (CRD) progression were studied in male Munich-Wistar rats subjected to 5/6 nephrectomy and treated with candesartan (Csn; n = 30) or enalapril (Ena; n = 27) from 5 wk postsurgery. Despite control of systolic blood pressure (SBP; 24 wk: Csn = 143 +/- 9; Ena = 148 +/- 8 mmHg), urinary protein excretion rates (U(pr)V) increased over 24 wk (Csn = 92 +/- 10; Ena = 99 +/- 8mg/day). Glomerulosclerosis scores (GS) at 24 wk were similar for Csn (42 +/- 7%) vs. Ena (42 +/- 4%), values close to those of untreated controls at 12 wk (43 +/- 4%). At 24 wk, SBP and UprV correlated strongly with GS, together accounting for 72% of the variance in GS. Renal cortex mRNA levels (determined by competitive RT-PCR) for transforming growth factor (TGF)-beta1 and monocyte chemoattractant protein (MCP)-1 were elevated in Csn and Ena at 12 wk and remained higher at 24 wk vs. sham. Strong correlations were evident among TGF beta1, MCP-1, and interleukin-1beta and renal injury at 24 wk. Cns and Ena are thus equally effective renoprotective agents in this model. During renin angiotensin system inhibition, renoprotection is dependent on control of both SBP and UprV. Incomplete suppression of renal cytokine gene expression may also contribute to CRD progression. PMID- 11208611 TI - Pendrin: an apical Cl-/OH-/HCO3- exchanger in the kidney cortex. AB - The identities of the apical Cl-/base exchangers in kidney proximal tubule and cortical collecting duct (CCD) cells remain unknown. Pendrin (PDS), which is expressed at high levels in the thyroid and its mutation causes Pendred's syndrome, is shown to be an anion exchanger. We investigated the renal distribution of PDS and its function. Our results demonstrate that pendrin mRNA expression in the rat kidney is abundant and limited to the cortex. Proximal tubule suspensions isolated from kidney cortex were highly enriched in pendrin mRNA. Immunoblot analysis studies localized pendrin to cortical brush-border membranes. Nephron segment RT-PCR localized pendrin mRNA to proximal tubule and CCD. Expression studies in HEK-293 cells demonstrated that pendrin functions in the Cl-/OH-, Cl-/HCO3-, and Cl-/formate exchange modes. The conclusion is that pendrin is an apical Cl-/base exchanger in the kidney proximal tubule and CCD and mediates Cl-/OH-, Cl-/HCO3-, and Cl-/formate exchange. PMID- 11208612 TI - Tuberculosis elimination: are we willing to pay the price? PMID- 11208613 TI - Pressure-volume curves: searching for the grail or laying patients with adult respiratory distress syndrome on procrustes' bed? PMID- 11208614 TI - Reducing asthma mortality with the asthma self-management plan system of care. PMID- 11208615 TI - The link between sleep apnea and cardiovascular disease: time to target the nonsleepy sleep apneics? PMID- 11208616 TI - What nobody needs to know about airborne infection. PMID- 11208617 TI - The buck stops here. PMID- 11208618 TI - The COMPACCS Study: questions left unanswered. The Committee on Manpower for Pulmonary and Critical Care Societies. PMID- 11208619 TI - Are asthma medications and management related to deaths from asthma? AB - There is controversy about the role of beta-agonists in asthma mortality, and the impact of asthma management plans remains unclear. We compared blood beta-agonist levels in patients dying from asthma with those in controls, and estimated the risks associated with specific classes of medication and patterns of management. We identified 89 asthma deaths and recruited 322 patients presenting to hospitals with acute asthma. A questionnaire was administered to the next of kin in 51 cases, and to 202 controls. Blood drawn from 35 cases and 229 controls was assayed for salbutamol. Smoking, drinking, and family problems were significantly more likely among the cases of asthma death than among the controls. The two groups were reasonably well matched with regard to markers of chronic asthma severity. Cases of asthma death were significantly less likely than controls to use a peak flow meter. Written action plans were associated with a 70% reduction in the risk of death. Use of nebulized bronchodilators or oral steroids was significantly more likely in cases of asthma death. Mean blood salbutamol concentrations were 2.5 times higher in cases of asthma. The use of oral steroids for an attack of asthma reduced the risk of death by 90%. More widespread adoption of written asthma management plans, with less reliance on beta-agonists and closer medical supervision, should reduce asthma mortality. PMID- 11208620 TI - Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. AB - Disordered breathing during sleep is associated with acute, unfavorable effects on cardiovascular physiology, but few studies have examined its postulated association with cardiovascular disease (CVD). We examined the cross-sectional association between sleep- disordered breathing and self-reported CVD in 6,424 free-living individuals who underwent overnight, unattended polysomnography at home. Sleep-disordered breathing was quantified by the apnea-hypopnea index (AHI) the average number of apneas and hypopneas per hour of sleep. Mild to moderate disordered breathing during sleep was highly prevalent in the sample (median AHI: 4.4; interquartile range: 1.3 to 11.0). A total of 1,023 participants (16%) reported at least one manifestation of CVD (myocardial infarction, angina, coronary revascularization procedure, heart failure, or stroke). The multivariable-adjusted relative odds (95% CI) of prevalent CVD for the second, third, and fourth quartiles of the AHI (versus the first) were 0.98 (0.77-1.24), 1.28 (1.02-1.61), and 1.42 (1.13-1.78), respectively. Sleep-disordered breathing was associated more strongly with self-reported heart failure and stroke than with self-reported coronary heart disease: the relative odds (95% CI) of heart failure, stroke, and coronary heart disease (upper versus lower AHI quartile) were 2.38 (1.22-4.62), 1.58 (1.02- 2.46), and 1.27 (0.99-1.62), respectively. These findings are compatible with modest to moderate effects of sleep-disordered breathing on heterogeneous manifestations of CVD within a range of AHI values that are considered normal or only mildly elevated. PMID- 11208621 TI - Propofol versus midazolam regarding their antioxidant activities. AB - Propofol and midazolam are commonly used as sedatives for critically ill patients. These patients usually suffer from the pathologic effects of oxidative stress, predominantly caused by an imbalance between the generation of reactive oxygen species and the antioxidant defense system. Therefore, the antioxidant activities of propofol and midazolam may be of clinical importance. We investigated the activities of these two sedatives against hydrophilic or lipophilic peroxyl radicals in a homogeneous solution and in the presence of erythrocyte membranes. A chemical analysis of the homogeneous solution revealed that propofol efficiently scavenged hydrophilic peroxyl radicals (50% inhibitory concentration [IC50] = 1.3 x 10(-4) M), whereas midazolam efficiently scavenged lipophilic radicals (IC50 = 1.5 x 10(-5) M). Further, in membrane systems, propofol inhibited the oxidative damage induced by either hydrophilic or lipophilic radicals (IC50 = 1.5 x 10(-5) M for hydrophilic radicals and IC50 = 3.0 x 10(-4) M for lipophilic radicals), whereas midazolam did very little. In previous studies, we demonstrated that antioxidant activity is highly affected by the location and properties of the reaction site. The discrepancy in antioxidant activity between a homogeneous condition and in the presence of membranes can be well explained by this concept, and again emphasizes the importance of membranes in determining antioxidant activity. To further understand the biologic significance of these antioxidant properties, the effect of the two agents on endothelium-dependent relaxation was studied. Application of oxidative stress to aortic rings by treating them with peroxyl radicals led to a significant blockade of acetylcholine-induced relaxation after submaximal contraction with phenylephrine. Propofol pretreatment greatly attenuated the impairment in comparison with midazolam, which agrees with the concept of antioxidant activity in the presence of membranes. The results of the present study suggest that propofol has a greater potential to reduce oxidative stress than midazolam. PMID- 11208622 TI - Acute anti-inflammatory effects of inhaled budesonide in asthma: a randomized controlled trial. AB - Corticosteroids can have acute effects on airway function and methacholine airway responsiveness in asthma as early as 6 h after dosing, suggesting there may be an acute anti-inflammatory effect of inhaled corticosteroid in asthma. This study aimed to determine the effects of a single dose of inhaled budesonide on sputum eosinophils and mast cells in adults with asthma, and to examine whether the mechanism of clearance of eosinophils was by apoptosis. A randomized, double blind, placebo-controlled, crossover study was conducted. At the screening visit, adults with stable asthma (n = 41) ceased inhaled corticosteroid therapy for 4 d and those with significant sputum eosinophilia (> or = 7%) were randomized (n = 26) to a single dose of budesonide 2,400 microg or placebo via Turbuhaler, on two separate study days. Symptoms and lung function were followed for 6 h, then sputum was induced and airway responsiveness to hypertonic saline determined. Sputum eosinophils (mean, SE) were significantly lower 6 h after budesonide (25%, 4.5), compared with placebo (37%, 6.2, p < 0.05). There was a 2.2-fold (95% CI 1.45 to 3.33) improvement in airway responsiveness with budesonide. No significant difference was seen on mast cells, apoptotic eosinophils, symptoms, or lung function. In conclusion, a single dose of inhaled corticosteroids has beneficial effects on airway inflammation and airway hyperresponsiveness as early as 6 h after dosing. This may be clinically useful as therapy during mild exacerbations of asthma. PMID- 11208623 TI - Airway responsiveness in early infancy predicts asthma, lung function, and respiratory symptoms by school age. AB - Asthma is the most common chronic childhood disease in developed nations. Little is known about the relationship between airway responsiveness in infancy and the development of asthma later in life. The relationship of airway responsiveness at 1 mo with asthma, atopy, lower respiratory symptoms, and lung function at 6 yr of age was investigated prospectively in 95 white children from a randomly ascertained birth cohort. Baseline spirometry, airway responsiveness to histamine, and skin reactivity to common allergens were assessed at the age of 1 mo and 6 yr. Total serum immunoglobulin E (IgE) was measured from cord blood and at 6 yr. Blood eosinophil counts were measured at 6 yr only. Family, symptom, and exposure histories at both time points were derived from questionnaire data. Independently of the other factors assessed, increased airway responsiveness at 1 mo was significantly associated with the following parameters measured at six yr: decreased FEV(1) (p < 0.001); decreased FVC (p < 0.001); physician-diagnosed asthma (p < 0.001); and lower respiratory tract symptoms (p < 0.05). None of the other physiologic factors measured in infancy showed such consistent associations with important clinical and physiologic outcomes at age 6. These data suggest that airway responsiveness in early life defines a functional state that is associated with abnormal airway function, lower respiratory symptoms, and the emergence of asthma by 6 yr of age. PMID- 11208624 TI - Infection with Burkholderia cepacia in cystic fibrosis: outcome following lung transplantation. AB - As a result of concern over excessive mortality after lung transplantation, many transplant programs refuse to accept cystic fibrosis (CF) patients infected with Burkholderia cepacia. As a significant proportion of patients with CF in our community are infected with this organism, we have continued to provide lung transplantation as an option. A retrospective review was conducted of medical records of all patients with CF transplanted between March 1988 and September 1996. Fifty-six transplant procedures were performed in 53 recipients with CF between March 1988 and September 1996. Twenty-eight had B. cepacia isolated pretransplant and 25 remaining positive post-transplant. Of the 53 recipients, 19 have died (15 of 28 [54%] B. cepacia positive and 4 of 25 [16%] B. cepacia negative). B. cepacia was responsible for or involved in 14 deaths. Nine of the deaths occurred in the first 3 mo post-transplantation. One-year survival was 67% for B. cepacia positive patients and 92% for B. cepacia negative patients. Recent modifications in antimicrobial and immunosuppressive therapy since 1995 have resulted in no deaths early post-transplant in the last five patients transplanted. We conclude that early mortality in patients with CF infected with B. cepacia is significantly higher than in those not infected with B. cepacia. Modifications in post-transplant medical therapy may improve outcome. PMID- 11208625 TI - Response of the canine internal intercostal muscles to chest wall vibration. AB - Although high-frequency mechanical vibration of the rib cage reduces dyspnea, its effects on the respiratory muscles are largely unknown. We have previously shown that in anesthetized dogs, vibrating the rib cage during inspiration elicits a marked increase in the inspiratory electromyographic (EMG) activity recorded from the external intercostal muscles but does not affect tidal volume (VT). In the present studies, we have tested the hypothesis that the maintenance of VT results from the concomitant contraction of the internal interosseous (expiratory) intercostals. When the rib cage was vibrated (40 Hz) during hyperventilation induced apnea, a prominent activity was recorded from the external intercostals but no activity was recorded from the internal intercostals, including when the muscles were lengthened by passive inflation. The internal intercostals remained also silent when vibration was applied during spontaneous inspiration, and the phasic expiratory EMG activity recorded from them was unaltered when vibration was applied during expiration. Thus, the internal interosseous intercostals in dogs are much less sensitive to vibration than the external intercostals, and they do not interfere with the action of these latter during rib cage vibration. This lack of sensitivity might be the result of a reflex inhibition of the muscle spindle afferents by afferents from external intercostal muscle spindles. PMID- 11208626 TI - Endogenous surfactant turnover in preterm infants with respiratory distress syndrome studied with stable isotope lipids. AB - We studied surfactant kinetics on Day 1 of life in 11 preterm infants on mechanical ventilation by infusing stable isotope labeled palmitic (PA) and linoleic acid (LLA). Six infants received exogenous surfactant for the treatment of respiratory distress syndrome (RDS) and five did not meet treatment criteria because of minimal or no disease. The isotopic enrichment of plasma free PA and LLA and of surfactant phosphatidylcholine PA (PC-PA) and LLA (PC-LLA) from tracheal aspirates was measured by mass spectrometry. Significant isotopic enrichment could be measured in PC-PA and PC-LLA from all patients. The fractional synthesis rate (FSR) of PC-LLA was higher than that of PC-PA (22.7 +/- 15.9 versus 12.1 +/- 7.7% per day, p = 0.018). Half-life (HL) of PC-PA was longer than that of PC-LLA (94.7 +/- 18.8 versus 46.6 +/- 32.6 h, p = 0.028). Patients who received exogenous surfactant had longer secretion times (ST) and delayed peak times (PK) but FSR and HL were unaffected. We concluded that: (1) surfactant kinetics can be measured in preterm infants with stable isotope labeled lipids; (2) surfactant FSR and HL calculated with PA and LLA gave different results; (3) patients treated with exogenous surfactant had similar FSRs compared with the nontreated subjects but had longer ST and delayed PK; (4) FSR from plasma free fatty acids (present study) was higher than that from plasma glucose in our previous work (Bunt JEH, Zimmermann LJI, Wattimena D, van Beek R, Sauer PJJ, Carnielli VP. Am J Respir Crit Care Med 1998;157:810-814) in a comparable population of preterm infants with RDS. PMID- 11208627 TI - Predictors of loss of lung function in the elderly: the Cardiovascular Health Study. AB - Pulmonary function, as measured by spirometry (FEV1 or FVC), is an important independent predictor of morbidity and mortality in elderly persons. In this study we examined the predictors of longitudinal decline in lung function for participants of the Cardiovascular Health Study (CHS). The CHS was started in 1990 as a population-based observational study of cardiovascular disease in elderly persons. Spirometry testing was conducted at baseline, 4 and 7 yr later. The data were analyzed using a random effects model (REM) including an AR(1) error structure. There were 5,242 subjects (57.6% female, mean age 73 yr, 87.5% white and 12.5% African-American) with eligible FEV1 measures representing 89% of the baseline cohort. The REM results showed that African-Americans had significantly lower spirometry levels than whites but that their rate of decline with age was significantly less. Subjects reporting congestive heart failure (CHF), high systolic blood pressure (> 160 mm Hg), or taking beta-blockers had significantly lower spirometry levels; however, the effects of high blood pressure and taking beta-blockers diminished with increasing age. Chronic bronchitis, pneumonia, emphysema, and asthma were associated with reduced spirometry levels. The most notable finding of these analyses was that current smoking (especially for men) was associated with more rapid rates of decline in FVC and FEV1. African-Americans (especially women) had slower rates of decline in FEV1 than did whites. Although participants with current asthma had a mean 0.5 L lower FEV1 at their baseline examination, they did not subsequently experience more rapid declines in FEV1. PMID- 11208628 TI - Best compliance during a decremental, but not incremental, positive end expiratory pressure trial is related to open-lung positive end-expiratory pressure: a mathematical model of acute respiratory distress syndrome lungs. AB - A mathematical model of the acute respiratory distress syndrome (ARDS) lung, incorporating simulated gravitational superimposed pressure and alveolar opening and closing pressures, was used to study the mean tidal pressure-volume (PV) slope ("effective compliance") during incremental and decremental positive end expiratory pressure (PEEP) trials with constant tidal volume (VT) "ventilation." During incremental PEEP, the PEEP giving maximum mean tidal PV slope did not coincide with "open lung PEEP" (minimum PEEP preventing end expiratory collapse of 97.5% of alveoli inflated at end-inspiration), and it varied greatly with varying VT and "lung mechanics." Incremental PEEP with a low VT tests recruitment by the peak pressure, not prevention of collapse by PEEP. During decremental PEEP with a low VT, maximum mean tidal PV slope occurred with PEEP 2-3.5 cm H2O below open-lung PEEP, unless closing pressure was high. High VT, high "specific compliance," and high opening pressures caused slightly greater underestimation of open-lung PEEP. Maximum mean tidal PV slope was always higher (e.g., 93.7 versus 16.69 ml/cm H2O), and the variation in PV slope with PEEP was greater, during decremental PEEP. The maximum PV slope during a decremental PEEP trial with a low VT may be a useful method to determine open-lung PEEP in ARDS, and should be studied clinically. PMID- 11208629 TI - Pretreatment with FK506 improves survival rate and gas exchange in canine model of acute lung injury. AB - The novel effects of FK506 on shock induced by lipopolysaccharide and phorbol myristate acetate (LPS/PMA) were studied using beagles. Five groups were studied: endotoxin shock control group (both 0.5 mg/kg of LPS and 30 microg/kg of PMA, n = 6); methylprednisolone-treated endotoxin shock group (n = 5); FK506-treated endotoxin shock groups in which intravenous infusions of FK506 at 2.5 microg/kg/h (low dose, n = 5), 8 microg/kg/h (medium dose, n = 5), and 25 microg/kg/h (high dose, n = 5) were administered. In the control group, the survival rate was 33%. Also, arterial hypoxemia, systemic hypotension, and marked increases in pulmonary vascular resistance (PVR) and wet-to-dry weight ratio (W/D) were observed. FK506 treatment at both medium and high doses significantly attenuated these LPS/PMA induced physiological changes, and the survival rates were 80 and 100%, respectively. On the other hand, in the methylprednisolone group, no obvious effects were observed. The present study suggests that FK506 could have prophylactic potential against acute lung injury in endotoxin shock. PMID- 11208630 TI - Regular versus as-needed short-acting inhaled beta-agonist therapy for chronic obstructive pulmonary disease. AB - Regular short-acting inhaled beta-agonist therapy is of uncertain benefit in patients with chronic obstructive pulmonary disease (COPD). We conducted a randomized, concealed, double-blind, placebo-controlled crossover trial in two periods, each of 3-mo duration, involving 53 patients with a smoking history of > 20 pack-years, an FEV1 of < 70% predicted, and an FEV1/VC ratio of < 0.7 after inhalation of 200 microg albuterol. All patients received regular ipratropium bromide at 20 microg per puff in 2 puffs four times daily, beclomethasone at 250 microg per puff or equivalent corticosteroid in 2 puffs twice daily, and open label inhaled albuterol as needed. Interventional therapy consisted of regular inhaled albuterol (100 microg per puff, in 2 puffs four times daily) versus placebo. Patients used twice as much active albuterol in the regular use period (mean: 8.07 puffs of coded and 4.68 puffs of open-label medication; total: 12.75 puffs daily) than during the as-needed period (mean: 6.34 puffs of open-label albuterol daily). Despite greater beta-agonist use, patients showed similar results during treatment and control periods for all outcomes. Differences between active and placebo periods were: FEV1: -0.04 L (95% confidence interval [CI]: -0.09 to 0.01 L); slow vital capacity: 0.04 L (95% CI: -0.12 to 0.20 L); 6 min walk test distance: -3.1 m (95% CI: -16.8 to 10.5 m); and Chronic Respiratory Questionnaire scores for dyspnea: 0.02 (95% CI: -0.13 to 0.16); fatigue: -0.02 (95% CI: -0.25 to 0.20); mastery: 0.01 (95% CI: -0.20 to 0.24); and emotional function: 0.02 (95% CI: -0.20 to 0.24). We found that in patients with COPD, use of regular short-acting inhaled beta-agonists resulted in twice as much beta agonist use without physiologic or clinical benefit as did use on an as-needed basis. PMID- 11208631 TI - Static compliance of the respiratory system in healthy infants. AB - We recorded static deflation pressure-volume (PV) curves from near TLC to FRC in 49 healthy, sedated, spontaneously breathing infants of 1 to 104 wk of age. Respiratory activity was transiently inhibited by inflating the respiratory system several times to a volume at an airway pressure of 30 cm H2O (V30). Passive deflation from V30 to FRC was then interrupted by multiple brief occlusions at the airway opening, in order to measure static recoil pressures. The expired volume from V30 to FRC was defined as V30E. Compliance of the respiratory system (Crs) was calculated as the slope of the linear portion of the PV curve from 5 to 15 cm H2O. Crs and V30E increased with increasing body length (p < 0.001). After adjustment for body length, males had greater Crs values than did females (p < 0.01). V30E was smaller in female infants (p < 0.05) and in infants whose mothers smoked during pregnancy (p < 0.04). Specific compliance (Crs/V30E) declined with increasing age (p < 0.01), but there were no differences related to sex or maternal smoking. We conclude that static deflation PV curves can be recorded in the age range from 1 to 104 wk, and that maternal smoking may produce hypoplastic lungs. PMID- 11208632 TI - Alteration of fatty acid profiles in different pulmonary surfactant phospholipids in acute respiratory distress syndrome and severe pneumonia. AB - Impairment of alveolar surfactant function has been documented in the acute respiratory distress syndrome (ARDS) and in severe pneumonia (PNEU); however, the underlying mechanisms are not completely understood. In the current report we present a detailed analysis of fatty acid (FA) profiles of different surfactant phospholipid (PL) classes isolated from bronchoalveolar lavage fluids (BALF) and large surfactant aggregates (LSA) from mechanically ventilated patients with ARDS (n = 8), ARDS associated with lung infection (ARDS + PNEU, n = 9), and PNEU (n = 22). Healthy volunteers served as control subjects (n = 8). PLs were isolated by thin-layer chromatography, and the FA profile of each PL class was assessed by gas chromatography. In addition, the minimal surface tension (gamma min) of untreated LSA and of LSA after supplementation with additional dipalmitoylated phosphatidylcholine (DPPC) was analyzed (pulsating bubble surfactometer). As compared with control LSA, the percentage of palmitic acid in phosphatidylcholine (PC) was significantly decreased in all patient groups (ARDS 63.0 +/- 2.0%, ARDS + PNEU 64.6 +/- 4.9%, PNEU 65.6 +/- 1.5%, control subjects 80.1 +/- 1.7%), whereas the relative amount of unsaturated species in PC increased significantly in all groups. Phosphatidylglycerol (PG) and phosphatidylinositol (PI) presented similar FA profiles in control subjects, but differed in the patients. The FA pattern of sphingomyelin (SPH) and phosphatidylethanolamine (PE) displayed only minor changes under conditions of respiratory failure. As compared with control subjects a highly significant increase of gamma min from near zero to approximately 16 mN/m was observed in all patients and was found to be inversely correlated to the percentage of palmitic acid in PC of LSA or BALF. Accordingly, values for gamma min were significantly improved upon secondary supplementation of LSA with DPPC up to control values. We conclude that marked changes in the FA composition of the predominant surfactant PL classes occur, both in ARDS triggered by nonpulmonary events and PNEU. The marked reduction of palmitic acid in the PC fraction may be related to changes in surfactant function under these conditions. PMID- 11208633 TI - Effect of alpha4-integrin blockade on CD4+ cell-driven late airway responses in the rat. AB - The blockade of alpha4 integrins with a monoclonal antibody (TA-2) decreases late airway responses (LR) in ovalbumin (OVA)-sensitized and challenged rats. In this study, we used a model of CD4+ cell-driven LR to test the hypothesis that alpha4 integrin blockade involves interference with T-cell activation in the inhibition of LR. Purified CD4+ cells from OVA-sensitized rats were transferred to unsensitized recipients, which received either TA-2 or a control antibody (cAb), and were OVA-challenged. A sham-challenged group was also studied. LR, calculated from pulmonary resistance after challenge, were reduced in the TA-2 group compared with the cAb group (p = 0.015). Total cell counts, macrophages, neutrophils, and lymphocytes in bronchoalveolar lavage (BAL), and CD3+ cells in airway sections, were unaffected. The cAb group had higher numbers of cells expressing interleukin-5 (IL-5) mRNA (55.2 +/- 3.39 cells/1,000, mean +/- SEM) and major basic protein (MBP) (6.2 +/- 0.4/100 cells) in bronchoalveolar lavage (BAL), than the TA-2 group (25.37 +/- 2.41 IL-5+ and 2.7 +/- 0.2 MBP+) and the sham group (12.37 +/- 0.96 IL-5+, 1.7 +/- 0.1 MBP+). Interferon gamma (IFN-gamma) mRNA+ cells were downregulated in both OVA-challenged groups, compared with the sham group. Our results suggest that the attenuation of LR and eosinophilia by alpha4-integrin blockade may involve interference with CD4+ cell activation and IL-5 expression. PMID- 11208634 TI - Improvement in aerosol delivery with helium-oxygen mixtures during mechanical ventilation. AB - In mechanically ventilated patients with airway obstruction, helium-oxygen (He O2) mixtures reduce airway resistance and improve ventilation, but their influence on aerosol delivery is unknown. Accordingly, we determined the effect of various He-O2 mixtures on albuterol delivery from metered-dose inhalers (MDIs) and jet nebulizers in an in vitro model of mechanical ventilation. Albuterol delivery from a MDI was increased when the ventilator circuit contained 80% helium and 20% oxygen (He-O2 80/20) versus O2: 46.7 +/- 3.3 versus 30.2 +/- 1.3 (SE)% of the nominal dose (p < 0.001)-the difference was mainly due to decreased drug deposition in the spacer chamber, mean 39.2% and 55.2%, respectively (p < 0.001). Nebulizer efficiency at a flow rate of 6 L/min was five times lower with He-O2 80/20 than O2, and the amount of nebulized drug was inversely correlated with gas density (r = 0.94, p < 0.0001). When the nebulizer was operated with O2, greater albuterol delivery was achieved when the ventilator circuit contained He O2 rather than O2. In summary, He-O2 mixtures in the circuit increased aerosol delivery for both MDIs and nebulizers in the mechanically ventilated model by as much as 50%. In conclusion, at appropriate flow rates and concentrations, He-O2 in the ventilator circuit may improve aerosol delivery in mechanically ventilated patients with severe airway obstruction. PMID- 11208635 TI - Analysis of intracellular cytokines in CD4+ and CD8+ lung and blood T cells in sarcoidosis. AB - In pulmonary sarcoidosis, activated T cells accumulate in the lungs. We hypothesized that the balance between the T-helper type 1 (Th1) cytokines (interferon [IFN]-gamma and interleukin [IL]-2) and Th2 cytokines such as IL-4, IL-5, and IL-10 might explain differences in clinical outcome in pulmonary sarcoidosis, such as why patients of human leukocyte antigen (HLA) type DR17 have a much better prognosis than those of other HLA types. Peripheral blood lymphocytes (PBL) and lymphocytes obtained by bronchoalveolar lavage (BAL) from HLA-typed sarcoidosis patients, as well as PBL from healthy controls, were stimulated in vitro, fixed, and permeabilized with saponin. Thereafter, cells were stained with fluorescence- labeled antibodies specific for intracellular cytokines (IL-2, IL-4, IFN-gamma, and tumor necrosis factor (TNF)-alpha and cell surface markers CD4 and CD8, and were subjected to flow-cytometric analysis. In bronchoalveolar lavage fluid (BALF), there were significantly greater frequencies of T cells positive for IFN-gamma and TNF-alpha than there were among PBL, and significantly fewer cells positive for IL-4, in both the CD4+ and CD8+ subsets. HLA-DR17-positive patients showed a tendency toward a less pronounced Th1 response that may be related to their good prognosis. Sarcoidosis patients had higher frequencies of cells positive for IFN-gamma, IL-4, and IL-2 in their blood than did healthy controls, a finding that may reflect the systemic nature of sarcoidosis. A clear Th1 cytokine profile of CD4+ as well as of CD8+ T cells was demonstrated in BALF from sarcoidosis patients. This was most pronounced for CD8+ cells, which may therefore make an important contribution to the inflammatory process in the lungs in pulmonary sarcoidosis. PMID- 11208636 TI - Health status deterioration in patients with chronic obstructive pulmonary disease. AB - This study examined health status decline in patients with chronic obstructive pulmonary disease (COPD). Data are from the Inhaled Steroids in Obstructive Lung Disease (ISOLDE) trial. After an 8-wk run-in, 751 patients (566 male), mean age 64 yr, were randomized to receive fluticasone propionate (FP) 500 microg twice daily (376 patients) or placebo (375 patients). Mean baseline postbronchodilator FEV1 was 50 +/- 15% predicted. Patients completed the St George's Respiratory Questionnaire (SGRQ) and the Short-Form 36 (SF-36) at baseline and every 6 mo for 3 yr. FEV1 and smoking status were assessed at baseline and at 3-mo intervals. A total of 387 (212 FP) patients completed the trial. All SGRQ components (p = 0.03 to 0.004) and Physical Function, Mental Health, Energy/ Vitality, and Physical Role Limitation scales of the SF-36 (p = 0.05 to 0.005) deteriorated faster in the placebo group. FEV1 and SGRQ scores correlated at baseline values (r = -0.25, p < 0.0001), as did change in FEV1 and change in SGRQ (Delta r = -0.24, p < 0.0001). At baseline values smokers had worse SGRQ Total, Symptoms, and Impacts scores than ex-smokers. This difference was maintained throughout the study. Smoking status did not influence the rate of decline in health status. The SGRQ Total scores of FP-treated patients took 59% longer than placebo to deteriorate by a clinically significant amount. We conclude that health status decline in moderate to severe COPD can be reduced by high-dose fluticasone. PMID- 11208637 TI - Low-flow oxygen and bilevel ventilatory support: effects on ventilation during sleep in cystic fibrosis. AB - We measured ventilation in all sleep stages in patients with cystic fibrosis (CF) and moderate to severe lung disease, and compared the effects of low-flow oxygen (LFO2) and bilevel ventilatory support (BVS) on ventilation and gas exchange during sleep. Thirteen subjects, age 26 +/- 5.9 yr (mean +/- 1 SD), body mass index (BMI) 20 +/- 3 kg/m2, FEV1 32 +/- 11% predicted, underwent three sleep studies breathing, in random order, room air (RA), LFO2, and BVS +/- O2 with recording of oxyhemoglobin saturation (SpO2) (%) and transcutaneous carbon dioxide (TcCO2) (mm Hg). During RA and LFO2 studies, patients wore a nasal mask with a baseline continuous positive airway pressure (CPAP) of 4 to 5 cm H2O. Minute ventilation (V I) was measured using a pneumotachograph in the circuit and was not different between wake and non-rapid eye movement (NREM) sleep on any night. However, V I was reduced on the RA and LFO2 nights from awake to rapid eye movement (REM) (p < 0.01) and from NREM to REM (p < 0.01). On the BVS night there was no significant difference in V I between NREM and REM sleep. Both BVS and LFO2 improved nocturnal SpO2, especially during REM sleep (p < 0.05). The rise in TcCO2 seen with REM sleep with both RA and LFO2 was attenuated with BVS (p < 0.05). We conclude that BVS leads to improvements in alveolar ventilation during sleep in this patient group. PMID- 11208638 TI - Meeting the needs of intensive care unit patient families: a multicenter study. AB - Intensive care unit (ICU) caregivers should seek to develop collaborative relationships with their patients' family members, based on an open exchange of information and aimed at helping family members cope with their distress and allowing them to speak for the patient if necessary. We conducted a prospective multicenter study of family member satisfaction evaluated using the Critical Care Family Needs Inventory. Forty-three French ICUs participated in the study. ICU characteristics, patient and family member demographics, and data on satisfaction were collected. Factors associated with satisfaction were identified using a Poisson regression model. A total of 637 patients were included in the study, and 920 family members completed the questionnaire. Seven predictors of family satisfaction were found: one family-related factor, namely, family of French descent and six caregiver-related factors, namely, no perceived contradictions in information given by caregivers; information provided by a junior physician; patient to nurse ratio or=2.0 (group A); in the remaining 15 lesions, FFR was >or=0.75 and CFR<2.0 (group B). Minimum microvascular resistance, defined as the ratio of mean distal pressure to average peak blood flow velocity during maximum hyperemia, showed a large variability (overall range, 0.65 to 4.64 mm Hg x cm(-1) x s(-1)) and was significantly higher in group B than in group A (2.42+/-0.77 versus 1.91+/-0.70 mm Hg x cm(-1) x s(-1); P:=0.034). CONCLUSIONS: Our findings demonstrate the prominent role of microvascular resistance in modulating the relationship between FFR and CFR and emphasize the importance of combined pressure and flow velocity measurements to evaluate coronary lesion severity and microvascular involvement. PMID- 11208674 TI - Serial intravascular ultrasound analysis of the impact of lesion length on the efficacy of intracoronary gamma-irradiation for preventing recurrent in-stent restenosis. AB - BACKGROUND: The relation between lesion length and effectiveness of brachytherapy is not well studied. METHODS AND RESULTS: We compared serial (postintervention and follow-up) intravascular ultrasound findings in 66 patients with native coronary artery in-stent restenosis (ISR) who were treated with (192)Ir (15 Gy delivered 2 mm away from the radiation source). Patients were enrolled in the Washington Radiation for In-Stent Restenosis Trial (WRIST; ISR length, 10 to 47 mm; n=36) or Long WRIST (ISR length, 36 to 80 mm; n=30). External elastic membrane, stent, lumen, and intimal hyperplasia (IH; stent minus lumen) areas and source-to-target (intravascular ultrasound catheter to external elastic membrane) distances were measured. Postintervention stent areas were larger in WRIST and smaller in Long WRIST patients (P:<0.0001). At follow-up, maximum IH area significantly increased in both WRIST and Long WRIST patients (P:<0.0001 for both), but this increase was greater in Long WRIST patients (P:=0.0006). Similarly, minimum lumen cross-sectional area significantly decreased in both WRIST and Long WRIST patients (P:<0.05 and P:<0.0001, respectively), but this decrease was more pronounced in Long WRIST patients (P:=0.0567). The maximum source-to-target distance was longer in Long WRIST than in WRIST, and it correlated directly with ISR length (r=0.547, P:<0.0001). Overall, the change in minimum lumen area and the change in maximum IH area correlated with the maximum source-to-target distance (r=0.352, P:=0.0038 and r=0.523, P:<0.0001 for WRIST and Long WRIST, respectively). The variability (maximum/minimum) in IH area at follow-up also correlated with the maximum source-to-target distance (r=0.378, P:<0.0001). CONCLUSIONS: Brachytherapy may be less effective in longer ISR lesions because of the greater variability and longer source-to-target distances in diffuse ISR. PMID- 11208675 TI - Lack of neointimal proliferation after implantation of sirolimus-coated stents in human coronary arteries: a quantitative coronary angiography and three dimensional intravascular ultrasound study. AB - BACKGROUND: Restenosis remains an important limitation of interventional cardiology. Therefore, we aimed to determine the safety and efficacy of sirolimus (a cell-cycle inhibitor)-coated BX Velocity stents. METHODS AND RESULTS: Thirty patients with angina pectoris were electively treated with 2 different formulations of sirolimus-coated stents (slow release [SR], n=15, and fast release [FR], n=15). All stents were successfully delivered, and patients were discharged without clinical complications. Independent core laboratories analyzed angiographic and 3D volumetric intravascular ultrasound data (immediately after procedure and at 4-month follow-up). Eight-month clinical follow-up was obtained for all patients. There was minimal neointimal hyperplasia in both groups (11.0+/ 3.0% in the SR group and 10.4+/-3.0% in the FR group, P:=NS) by ultrasound and quantitative coronary angiography (in-stent late loss, 0.09+/-0.3 mm [SR] and 0.02+/-0.3 mm [FR]; in-lesion late loss, 0.16+/-0.3 mm [SR] and -0.1+/-0.3 mm [FR]). No in-stent or edge restenosis (diameter stenosis >or=50%) was observed. No major clinical events (stent thrombosis, repeat revascularization, myocardial infarction, or death) had occurred by 8 months. CONCLUSIONS: The implantation of sirolimus-coated BX Velocity stents is feasible and safe and elicits minimal neointimal proliferation. Additional placebo-controlled trials are required to confirm these promising results. PMID- 11208676 TI - Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia. AB - BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia is a genetic arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death. The electrocardiographic pattern of this ventricular tachycardia closely resembles the arrhythmias associated with calcium overload and the delayed afterdepolarizations observed during digitalis toxicity. We speculated that a genetically determined abnormality of intracellular calcium handling might be the substrate of the disease; therefore, we considered the human cardiac ryanodine receptor gene (hRyR2) a likely candidate for this genetically transmitted arrhythmic disorder. METHODS AND RESULTS: Twelve patients presenting with typical catecholaminergic polymorphic ventricular tachycardia in the absence of structural heart abnormalities were identified. DNA was extracted from peripheral blood lymphocytes, and single-strand conformation polymorphism analysis was performed on polymerase chain reaction-amplified exons of the hRyR2 gene. Four single nucleotide substitutions leading to missense mutations were identified in 4 probands affected by the disease. Genetic analysis of the asymptomatic parents revealed that 3 probands carried de novo mutations. In 1 case, the identical twin of the proband died suddenly after having suffered syncopal episodes. The fourth mutation was identified in the proband, in 4 clinically affected family members, and in none of 3 nonaffected family members in a kindred with 2 sudden deaths that occurred at 16 and 14 years, respectively, in the sisters of the proband. CONCLUSIONS: We demonstrated that, in agreement with our hypothesis, hRyR2 is a gene responsible for catecholaminergic polymorphic ventricular tachycardia. PMID- 11208677 TI - Increased mortality with oral platelet glycoprotein IIb/IIIa antagonists: a meta analysis of phase III multicenter randomized trials. AB - BACKGROUND: Numerous clinical trials have established the benefits of intravenous glycoprotein IIb/IIIa inhibition in the management of coronary artery disease. In contrast, the recent large-scale, placebo-controlled, randomized trials of the oral glycoprotein IIb/IIIa antagonists have failed to provide commensurate reductions in late composite ischemic end points despite potent inhibition of platelet aggregation. METHODS AND RESULTS: The ORs for death, myocardial infarction, urgent revascularization, and major bleeding from the 4 large-scale, placebo-controlled, randomized trials with oral glycoprotein IIb/IIIa inhibitors were calculated and combined. Stratification by low-dose or high-dose therapy and the use of concurrent aspirin was also undertaken. In 33 326 patients followed for >30 days, a consistent and statistically significant increase in mortality was observed with oral glycoprotein IIb/IIIa therapy (OR, 1.37; 95% CI, 1.13 to 1.66; P:=0.001). This effect was evident regardless of aspirin coadministration and treatment with either low-dose or high-dose therapy. Although a reduction in urgent revascularization was observed with oral glycoprotein IIb/IIIa inhibition, pooled analysis favored an increase in myocardial infarction that did not demonstrate statistical significance. CONCLUSIONS: Although we found a highly significant excess in mortality consistent across 4 trials with 3 different oral glycoprotein IIb/IIIa inhibitor agents, this was associated with a reduction in the need for urgent revascularization and no increase in myocardial infarction. These findings suggest the potential for a direct toxic effect with these agents and argue against a prothrombotic mechanism. Further investigation to elucidate the cause of this increased fatality risk is warranted. PMID- 11208678 TI - PPARalpha agonists inhibit tissue factor expression in human monocytes and macrophages. AB - BACKGROUND: Monocytic tissue factor (TF) expression may contribute to thrombogenicity associated with plaque rupture and may propagate thrombus formation at the site of vascular lesions. Induction of monocytic TF expression by endotoxin is mediated by the activation of transcription factors such as AP-1 and NF-kappaB. Both these signaling pathways are modulated by peroxisome proliferator-activated receptor-alpha (PPARalpha). Therefore, we have studied the effects of fibrates and other PPARalpha agonists on the expression of TF. METHODS AND RESULTS: We show that PPARalpha protein, like primary human monocytes, is also expressed in the human monocytic THP-1 cell line. Fenofibric acid, WY14643, and GW2331 inhibited TF mRNA upregulation after stimulation of THP-1 cells with lipopolysaccharide or interleukin-1ss. In primary human monocytes and macrophages, the lipopolysaccharide- or interleukin-1ss-mediated induction of TF activity was also inhibited by fenofibric acid, WY14643, or GW2331. CONCLUSIONS: These data indicate that activation of PPARalpha results in the downregulation of the TF gene. Our results suggest a novel role for PPARalpha in the control of atherosclerotic plaque thrombogenicity through its effects on TF expression in monocytes and macrophages. PMID- 11208680 TI - Immunomodulating therapy with intravenous immunoglobulin in patients with chronic heart failure. AB - BACKGROUND: Congestive heart failure (CHF) is characterized by enhanced immune activation, and immune-mediated mechanisms may play a pathogenic role in this disorder. Based on the immunomodulatory effects of intravenous immunoglobulin (IVIG), we hypothesized that IVIG could downregulate inflammatory responses in CHF patients and have potential beneficial effects on the left ventricular ejection fraction (LVEF). METHODS AND RESULTS: Forty patients with chronic symptomatic CHF and LVEF of <40%, stratified according to cause (ie, ischemic and idiopathic dilated cardiomyopathy), were randomized in a double-blind fashion to receive therapy with IVIG or placebo for a total period of 26 weeks. Our main findings were that (1) IVIG, but not placebo, induced a marked rise in plasma levels of the anti-inflammatory mediators interleukin (IL)-10, IL-1 receptor antagonist, and soluble tumor necrosis factor receptors; (2) significantly correlated with these anti-inflammatory effects, IVIG, but not placebo, induced a significant increase in LVEF from 26+/-2% to 31+/-3% (P:<0.01), and this was found independent of the cause of heart failure; and (3) N-terminal pro-atrial natriuretic peptide decreased significantly after induction therapy and continued to decrease toward the end of study during IVIG therapy (P:<0.001) but remained unchanged during placebo. CONCLUSIONS: We demonstrated an IVIG-induced change in the balance between inflammatory and anti-inflammatory cytokines that favored an anti-inflammatory net effect in CHF. This effect was significantly correlated with an improvement in LVEF, suggesting a potential for immunomodulating therapy in addition to optimal conventional cardiovascular treatment regimens in CHF patients. PMID- 11208679 TI - PPARalpha activators inhibit tissue factor expression and activity in human monocytes. AB - BACKGROUND: Tissue factor (TF), expressed on the surface of monocytes and macrophages in human atherosclerotic lesions, acts as the major procoagulant initiating thrombus formation in acute coronary syndromes. Peroxisome proliferator-activated receptor-alpha (PPARalpha), a nuclear receptor family member, regulates gene expression in response to certain fatty acids and fibric acid derivatives. Given that some of these substances reduce TF activity in patients, we tested whether PPARalpha activators limit TF responses in human monocytic cells. METHODS AND RESULTS: Pretreatment of freshly isolated human monocytes or monocyte-derived macrophages with PPARalpha activators WY14643 and eicosatetraynoic acid (ETYA) led to reduced lipopolysaccharide (LPS)-induced TF activity in a concentration-dependent manner (maximal reduction to 43+/-8% with 250 micromol/L WY14643 [P:<0.05, n=5] and to 42+/-12% with 30 micromol/L ETYA [P:>0.05, n=3]). Two different PPARgamma activators (15-deoxy(_Delta12,14) prostaglandin J(2) and BRL49653) lacked similar effects. WY14643 also decreased tumor necrosis factor-alpha protein expression in supernatants of LPS-stimulated human monocytes. Pretreatment of monocytes with WY14643 inhibited LPS-induced TF protein and mRNA expression without altering mRNA half-life. Transient transfection assays of a human TF promoter construct in THP-1 cells revealed WY14643 inhibition of LPS-induced promoter activity, which appeared to be mediated through the inhibition of nuclear factor-kappaB but not to be due to reduced nuclear factor-kappaB binding. CONCLUSIONS: PPARalpha activators can reduce TF expression and activity in human monocytes/macrophages and thus potentially reduce the thrombogenicity of atherosclerotic lesions. These data provide new insight into how PPARalpha-activating fibric acid derivatives and certain fatty acids might influence atherothrombosis in patients with vascular disease. PMID- 11208681 TI - Left ventricular hypertrophy with exercise and ACE gene insertion/deletion polymorphism: a randomized controlled trial with losartan. AB - BACKGROUND: Local cardiac renin-angiotensin systems may regulate left ventricular (LV) hypertrophic responses. The absence (deletion [D]) of a 287-bp marker in the ACE gene is associated with greater myocardial ACE levels and exercise-related LV growth than is its presence (insertion [I]), an effect potentially mediated through either increased activity of the cellular growth factor angiotensin II on the angiotensin type 1 (AT(1)) receptor or increased degradation of growth inhibiting kinins. We sought to confirm ACE genotype-associated exertional LV growth and to clarify the role of the AT(1) receptor in this association. METHODS AND RESULTS: One hundred forty-one British Army recruits homozygous for the ACE gene (79 DD and 62 II) were randomized to receive losartan (25 mg/d, a subhypotensive dose inhibiting tissue AT(1) receptors) or placebo throughout a 10 week physical training program. LV mass, determined by cardiac magnetic resonance, increased with training (8.4 g, P:<0.0001 overall; 12.1 versus 4.8 g for DD versus II genotype in the placebo limb, P:=0.022). LV growth was similar in the losartan arm: 11.0 versus 3.7 g for DD versus II genotypes (P:=0.034). When indexed to lean body mass, LV growth in the II subjects was abolished, whereas it remained in the DD subjects (-0.022 versus 0.131 g/kg, respectively; P:=0.0009). CONCLUSIONS: ACE genotype dependence of exercise-induced LV hypertrophy is confirmed. Additionally, LV growth in DD (unlike II) subjects is in excess of the increase in lean body mass. These effects are not influenced by AT(1) receptor antagonism with the use of losartan (25 mg/d). The 2.4-fold greater LV growth in DD men may be due to the effects of angiotensin II on other receptors (eg, angiotensin type 4) or lower degradation of growth-inhibitory kinins. PMID- 11208682 TI - Mechanical circulatory support for advanced heart failure: effect of patient selection on outcome. AB - BACKGROUND: Use of wearable left ventricular assist systems (LVAS) in the treatment of advanced heart failure has steadily increased since 1993, when these devices became generally available in Europe. The aim of this study was to identify in an unselected cohort of LVAS recipients those aspects of patient selection that have an impact on postimplant survival. METHODS AND RESULTS: Data were obtained from the Novacor European Registry. Between 1993 and 1999, 464 patients were implanted with the Novacor LVAS. The majority had idiopathic (60%) or ischemic (27%) cardiomyopathy; the median age at implant was 49 (16 to 75) years. The median support time was 100 days (4.1 years maximum). Forty-nine percent of the recipients were discharged from the hospital on LVAS; they spent 75% of their time out of the hospital. For a subset of 366 recipients, for whom a complete set of data was available, multivariate analysis revealed that the following preimplant conditions were independent risk factors for survival after LVAS implantation: respiratory failure associated with septicemia (odds ratio 11.2), right heart failure (odds ratio 3.2), age >65 years (odds ratio 3.01), acute postcardiotomy (odds ratio 1.8), and acute infarction (odds ratio 1.7). For patients without any of these factors, the 1-year survival after LVAS implantation including the posttransplantation period was 60%; for the combined group with at least 1 risk factor, it was 24%. CONCLUSIONS: Careful selection, specifically implantation before patients become moribund, and improvement of management may result in improved outcomes of LVAS treatment for advanced heart failure. PMID- 11208683 TI - Overnight shift from obstructive to central apneas in patients with heart failure: role of PCO2 and circulatory delay. AB - BACKGROUND: Obstructive (OSA) and central sleep apnea (CSA) can coexist in patients with congestive heart failure (CHF). However, the reason why OSA events occur at one time and CSA events at another has not been determined. We hypothesized that a change in PCO(2) would be associated with an alteration in apnea type: a decrease in PCO(2) should lead to CSA. METHODS AND RESULTS: To test this hypothesis, we evaluated minute ventilation (V(I)), transcutaneous PCO(2) (PtcCO(2)), circulation time, and periodic breathing cycle length during overnight polysomnography in 12 patients with CHF and coexisting OSA and CSA. V(I) was significantly greater (mean+/-SEM, 9.4+/-1.3 versus 8.0+/-0.9 L/min; P:<0.05) and PtcCO(2) was lower (39.4+/-1.0 versus 41.9+/-1.1 mm Hg, P:<0.01) during episodes of CSA than of OSA. These changes were associated with significant lengthening of circulation time (23.6+/-3.7 versus 21.1+/-3.6 seconds, P:<0.01) and periodic breathing cycle length (53.7+/-3.5 versus 49.6+/ 2.9 seconds, P:<0.01). In addition, the proportion of obstructive events decreased (from 68.5+/-11.4% to 22.5+/-7.2%, P:<0.001) and of CSA events increased (from 31.5+/-11.4% to 77.5+/-7.2%, P:<0.001) from the first to the last quarter of the night in association with a significant decrease in PtcCO(2) (from 42.6+/-0.9 to 40.8+/-0.9 mm Hg, P:<0.01). CONCLUSIONS: In patients with CHF, the shift from OSA to CSA is associated with a reduction in PCO(2). This appears to be related to an overnight deterioration in cardiac function as suggested by the concurrent lengthening of circulation time. Therefore, in CHF patients, alterations in cardiac function may influence apnea type. PMID- 11208684 TI - "Stable" ventricular tachycardia is not a benign rhythm : insights from the antiarrhythmics versus implantable defibrillators (AVID) registry. AB - BACKGROUND: Sustained ventricular tachycardia (VT) can be unstable, can be associated with serious symptoms, or can be stable and relatively free of symptoms. Patients with unstable VT are at high risk for sudden death and are best treated with an implantable defibrillator. The prognosis of patients with stable VT is controversial, and it is unknown whether implantable cardioverter defibrillator therapy is beneficial. METHODS AND RESULTS: Screening for the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial identified patients with both stable and unstable VT. Both groups were included in a registry, and their clinical characteristics and discharge treatments were recorded. Mortality data were obtained through the National Death Index. The mortality in 440 patients with stable VT tended to be greater than that observed in 1029 patients presenting with unstable VT (33.6% versus 27.6% at 3 years; relative risk [RR]=1.22; P:=0.07). After adjustment for baseline and treatment differences, the RR was little changed (RR=1.25, P:=0.06). CONCLUSIONS: Sustained VT without serious symptoms or hemodynamic compromise is associated with a high mortality rate and may be a marker for a substrate capable of producing a more malignant arrhythmia. Implantable cardioverter-defibrillator therapy may be indicated in patients presenting with stable VT. PMID- 11208685 TI - Chemical cardioversion of atrial fibrillation or flutter with ibutilide in patients receiving amiodarone therapy. AB - BACKGROUND: Ibutilide is a class III drug that is used for the cardioversion of atrial arrhythmias, but it can cause torsade de pointes. Amiodarone also prolongs the QT interval but rarely causes torsade de pointes. There are no studies in which the concomitant use of the 2 agents was examined. The purpose of the present study was to assess the efficacy and safety of cardioversion with combination therapy in patients with atrial fibrillation or flutter. METHODS AND RESULTS: The study included 70 patients who were treated with long-term oral amiodarone and were referred for elective cardioversion of atrial fibrillation (57 of 70, 81%) or flutter (13 of 70, 19%). Patients were taking amiodarone (153+/-259 days, mean+/-SD) and were administered 2 mg intravenous ibutilide. Left ventricular ejection fraction was measured with echocardiography. The QT intervals were measured on 12-lead ECG. Fifty-five patients (79%) had structural heart disease. Patients were in arrhythmia for 196+/-508 days before cardioversion, with a left ventricular ejection fraction of 50+/-11%. In patients with atrial fibrillation, 22 (39%) of 57 and 7 (54%) of 13 patients with flutter converted within 30 minutes of infusion. Thirty-nine patients who did not convert after ibutilide were treated with electrical cardioversion, and 35 (90%) of 39 patients were successfully converted. The QT intervals were further prolonged after ibutilide for the group from 371+/-61 to 479+/-92 ms (P:<0.001). There was 1 episode of nonsustained torsade de pointes (1 of 70, 1.4%) after ibutilide. CONCLUSIONS: The use of ibutilide converted 54% of patients with atrial flutter and 39% of patients with atrial fibrillation who were treated with long-term amiodarone. Despite QT-interval prolongation after ibutilide, only 1 episode of torsade de pointes occurred. Our observations suggest that combination therapy may be a useful cardioversion method for chronic atrial fibrillation or flutter. PMID- 11208687 TI - Regulation of plasma endothelin by salt in salt-sensitive hypertension. AB - BACKGROUND: Salt dependency of blood pressure (BP) characterizes most models of experimental hypertension in which endothelins play a significant vasoconstrictor role. Despite this, there are no data on the regulation of plasma endothelin by salt balance in human hypertension. METHODS AND RESULTS: Plasma endothelin was measured in 47 patients with essential hypertension. Endothelin, catecholamine, and plasma renin activity (PRA) responses to 24-hour sodium deprivation (decreasing Na) were assessed in 29 of these patients. Endothelin was higher in hypertensive patients (4.6+/-0.2 fmol/mL) than in 20 control subjects (3.3+/-0.3 fmol/mL, P:<0.002), was correlated with BP, and was negatively associated with PRA (P:<0.04). Salt-sensitive, salt-resistant, and indeterminate groups were defined by the tertiles of the t statistic for the difference in BP before and after decreasing Na. Systolic BP falls were -15+/-1, -2+/-2, and -9+/-1 mm Hg, respectively. PRA, its response to decreasing Na, and its level after decreasing Na were lowest (albeit nonsignificant) in salt-sensitive patients. Baseline catecholamine and endothelin levels did not differ among the groups. In response to decreasing Na, catecholamines increased more significantly in salt-sensitive patients (+2.4+/-0.9 nmol/L) than in the other groups (0.4+/-0.2 and 0.7+/-0.2 nmol/L for indeterminate and salt-resistant groups, respectively; P:<0.03), whereas endothelin increased in the salt-sensitive group (0.8+/-0.3 fmol/mL), decreased in the salt-resistant group (-0.4+/-0.3 fmol/mL), and sustained minimal change in the indeterminate group (0.2+/-0.3 fmol/mL) (P:<0.04). Thus, endothelin levels in the salt-depleted state were highest in salt-sensitive patients (5.2+/ 0.4 fmol/mL) versus the other groups (3.4+/-0.4 and 4.4+/-0.4 fmol/mL for salt resistant and indeterminate groups, respectively) (P:<0.02). Changes in endothelin during decreasing Na and levels after decreasing Na were correlated with changes in catecholamines (P:<0.02). CONCLUSIONS: -Our data suggest that salt-depleted salt-sensitive hypertensives with blunted renin responses exhibit enhanced catecholamine-stimulated endothelin levels and may therefore respond better than unselected patients with essential hypertension to endothelin receptor blockers. PMID- 11208686 TI - The phytoestrogen genistein produces acute nitric oxide-dependent dilation of human forearm vasculature with similar potency to 17beta-estradiol. AB - BACKGROUND: Genistein, a phytoestrogen, may have estrogenic cardioprotective actions. We investigated whether genistein influences endothelium-dependent vasodilation in forearm vasculature of healthy human subjects and compared the effects of genistein with those of 17beta-estradiol. METHODS AND RESULTS: The brachial arterial was cannulated with a 27-gauge needle for drug infusion. Forearm blood flow responses were measured with strain-gauge plethysmography. Genistein (10 to 300 nmol/min, each dose for 6 minutes) produced a dose-dependent increase in forearm blood flow from 3.4+/-0.3 to 9.6+/-1.3 mL x min(-1) x 100 mL forearm(-1) (mean+/-SEM) in men (n=9, P:<0.0001 by ANOVA). The mean forearm venous concentration of genistein during infusion of the highest dose was 1.8+/ 0.3 micromol/L in 6 additional men. Genistein produced a similar increase in blood flow in premenopausal women. Daidzein, another phytoestrogen, was ineffective, but equimolar concentrations of 17beta-estradiol caused similar vasodilation to genistein. Responses to genistein and 17beta-estradiol were inhibited to the same degree by the NO synthase inhibitor N:(G)-monomethyl-L arginine. A threshold dose of genistein potentiated the endothelium-dependent vasodilator acetylcholine but not the endothelium-independent vasodilator nitroprusside. CONCLUSIONS: Genistein causes L-arginine/NO-dependent vasodilation in forearm vasculature of human subjects with similar potency to 17beta-estradiol and potentiates endothelium-dependent vasodilation to acetylcholine. PMID- 11208688 TI - Ventricular preexcitation in children and young adults: atrial myocarditis as a possible trigger of sudden death. AB - BACKGROUND: Sudden death (SD) in ventricular preexcitation (VP) syndrome is believed to be the result of atrial fibrillation with rapid ventricular response over the accessory pathway. Previous reports are anecdotal and often lack autopsy validation. METHODS AND RESULTS: Prevalence and clinicopathological features of VP were investigated in a series of 273 SDs in children and young adults (aged or=0.01 micromol/L) also reduced growth, proteolytic activity due to MMP-9, and TF expression in cultured human monocyte/macrophages. CONCLUSIONS: These results suggest that lipid lowering with HMG-CoA reductase inhibitors alters plaque biology by reducing proliferation and activation of macrophages, prominent sources of molecules responsible for plaque instability and thrombogenicity. PMID- 11208690 TI - Role of Rho-associated kinase in neointima formation after vascular injury. AB - BACKGROUND: The Rho/Rho-associated kinase (Rho-kinase) system is implicated in various cellular functions, including migration, proliferation, and apoptosis. Because a possible role of the system is suggested in neointima formation after vascular injury, we sought to examine whether a new specific Rho-kinase inhibitor, Y27632, prevents neointima formation of the balloon-injured rat carotid artery, and if so, to investigate the effects of Y27632 on migration, proliferation, and apoptosis of smooth muscle cells (SMCs) in the injured artery. METHODS AND RESULTS: Y27632 was administered intraperitoneally from 1 day before to 14 days after vascular injury. Treatment with Y27632 inhibited phenylephrine induced Rho-kinase activation in the carotid artery on the basis of immunoblotting against the phosphorylated myosin-binding subunit of myosin phosphatase. Y27632 markedly prevented neointima formation at days 7 and 14. In controls, BrdU(+) proliferating and TUNEL(+) apoptotic SMCs were transiently and coincidentally increased in the neointima, with a peak at day 7. Y27632 significantly increased the neointimal TUNEL(+) SMCs at days 7 and 14, but not BrdU(+) SMCs. Y27642 significantly decreased the number of intimal SMCs at day 4, while not affecting the number of BrdU(+) or TUNEL(+) SMCs. Reendothelialization after balloon injury was not significantly affected by Y27632 at days 7 and 14. CONCLUSIONS: Y27632 inhibited neointima formation by enhancing SMC apoptosis and probably by suppressing early SMC migration. Therefore, a role of Rho-kinase is suggested in neointima formation after vascular injury. PMID- 11208691 TI - Morphine mimics preconditioning via free radical signals and mitochondrial K(ATP) channels in myocytes. AB - BACKGROUND: We tried to determine whether morphine mimics preconditioning (PC) to reduce cell death in cultured cardiomyocytes and whether opioid delta(1) receptors, free radicals, and K(ATP) channels mediate this effect. METHODS AND RESULTS: Chick embryonic ventricular myocytes were studied in a flow-through chamber while flow rate, pH, and O(2) and CO(2) tension were controlled. Cardiomyocyte viability was quantified with propidium iodide (5 micromol/L), and production of free radicals was measured with 2',7'-dichlorofluorescin diacetate. PC with 10 minutes of simulated ischemia before 10 minutes of reoxygenation or morphine (1 micromol/L) or BW373U86 (10 pmol/L) infusion for 10 minutes followed by a 10-minute drug-free period before 1 hour of ischemia and 3 hours of reoxygenation reduced cell death to the same extent (*P:<0.05) (PC, 20+/-1%, n=7*; morphine, 32+/-4%, n=8*; BW373U86, 21+/-6%; controls, 52+/-5%, n=8). Like PC, morphine and BW373U86 increased free radical production 2-fold before ischemia (0.35+/-0.10, n=6*; 0.41+/-0.08, n=4* versus controls, 0.15+/-0.05, n=8, arbitrary units). Protection and increased free radical signals during morphine infusion were abolished with either the thiol reductant 2-mercaptopropionyl glycine (400 micromol/L), an antioxidant; naloxone (10 micromol/L), a nonselective morphine receptor antagonist; BNTX (0.1 micromol/L), a selective opioid delta(1) receptor antagonist; or 5-hydroxydecanoate (100 micromol/L), a selective mitochondrial K(ATP) channel antagonist. CONCLUSIONS: These results suggest that direct stimulation of cardiocyte opioid delta(1) receptors leads to activation of mitochondrial K(ATP) channels. The resultant increase of intracellular free radical signals may be an important component of the signaling pathways by which morphine mimics preconditioning in cardiomyocytes. PMID- 11208692 TI - Low-energy laser irradiation reduces formation of scar tissue after myocardial infarction in rats and dogs. AB - BACKGROUND: Low-energy laser irradiation (LELI) has been found to attenuate various biological processes in tissue culture and experimental animal models. The aim of the present study was to investigate the effect of LELI on the formation of scar tissue in experimentally induced chronic infarct in rats and dogs. METHODS AND RESULTS: Myocardial infarction (MI) was induced in 50 dogs and 26 rats by ligation of the left anterior descending coronary artery. After induction of MI, the laser-irradiated (LI) group received laser irradiation (infrared laser, 803-nm wavelength) epicardially. Control MI-induced non-laser irradiated (NLI) dogs were sham-operated, and laser was not applied. All dogs were euthanized at 5 to 6 weeks after MI. Infarct size was determined by TTC staining and histology. The laser treatment (P:<0.05) lowered mortality significantly, from 30% to 6.5%, after induction of MI. The infarct size in the LI dogs was reduced significantly (P:<0.0001) (52%) compared with NLI dogs. Histological observation of the infarct revealed a typical scar tissue in NLI dogs and cellularity in most of the LI dogs. Only 14+/-3% of the mitochondria in the cardiomyocytes in the ischemic zone (4 hours after MI) of LI MI-induced rats were severely damaged, compared with 36+/-1% in NLI rats. Accordingly, ATP content in that zone was 7.6-fold (significantly) higher in LI than in NLI rats. CONCLUSIONS: Our observations indicate that epicardial LELI of rat and dog hearts after chronic MI caused a marked reduction in infarct size, probably due to a cardioprotective effect of the LELI. PMID- 11208693 TI - Oral matrix metalloproteinase inhibition and arterial remodeling after balloon dilation: an intravascular ultrasound study in the pig. AB - BACKGROUND: Inhibition of matrix metalloproteinase (MMP) activity after balloon angioplasty by intraperitoneal injection of batimastat reduces late lumen loss by inhibition of constrictive remodeling. In the present study, we investigated whether the oral MMP inhibitor marimastat inhibits constrictive remodeling in favor of neutral or expansive remodeling. METHODS AND RESULTS: In 26 pigs, balloon dilation was performed in 101 peripheral arteries. Pigs were treated with marimastat or served as controls and were euthanized 42 days after intervention. Intravascular ultrasound was performed at all time points. Vessel area (VA) loss was assessed by calculating the change in VA at termination relative to after intervention. Arteries were divided in 3 categories: expansive remodeling (VA loss < -5%), neutral (-5% +5%). In the marimastat group, a significant reduction (53%) of late lumen loss was observed that was fully explained by impaired constrictive remodeling. In the marimastat group, the prevalence of constrictive remodeling was reduced (38% versus 75% in the control group) in favor of not only neutral but also expansive remodeling (21% and 42% versus 4% and 21% in the control group, respectively, P:<0.01). In contrast to the control group, acute luminal gain in the marimastat group did not correlate with late VA loss. CONCLUSIONS: Irrespective of the acute luminal gain by balloon dilation, the oral MMP inhibitor marimastat inhibited constrictive arterial remodeling in favor of both neutral and expansive remodeling. PMID- 11208694 TI - Treatment with a growth hormone secretagogue in a model of developing heart failure: effects on ventricular and myocyte function. AB - BACKGROUND: Exogenous administration of growth hormone (GH) and subsequently increased production of insulin-like growth factor-1 can influence left ventricular (LV) myocardial growth and geometry in the setting of congestive heart failure (CHF). This study determined the effects of an orally active GH secretagogue (GHS) treatment that causes a release of endogenous GH on LV function and myocyte contractility in a model of developing CHF. METHODS AND RESULTS: Pigs were randomly assigned to the following treatment groups: (1) chronic rapid pacing at 240 bpm for 3 weeks (n=11); (2) chronic rapid pacing and GHS (CP-424,391 at 10 mg x kg(-1) x d(-1), n=9); and (3) sham controls (n=8). In the untreated pacing CHF group, LV fractional shortening was reduced (21+/-2% versus 47+/-2%) and peak wall stress increased (364+/-21 versus 141+/-5 g/cm(2)) from normal control values (P:<0.05). In the GHS group, LV fractional shortening was higher (29+/-2%) and LV peak wall stress lower (187+/-126 g/cm(2)) than untreated CHF values (P:<0.05). With GHS treatment, the ratio of LV mass to body weight increased by 44% from untreated values. Steady-state myocyte velocity of shortening was reduced with pacing CHF compared with controls (38+/-1 versus 78+/ 1 microm/s, P:<0.05) and was increased from pacing CHF values with GHS treatment (55+/-7 microm/s, P:<0.05). CONCLUSIONS: The improved LV pump function that occurred with GHS treatment in this model of CHF was most likely a result of favorable effects on LV myocardial remodeling and contractile processes. On the basis of these results, further studies are warranted to determine the potential role of GH secretagogues in the treatment of CHF. PMID- 11208695 TI - Effectiveness of a nonselective ET(A/B) and a selective ET(A) antagonist in rats with monocrotaline-induced pulmonary hypertension. AB - BACKGROUND: Both nonselective ET(A/B) receptor and selective ET(A) receptor antagonists can reduce pulmonary hypertension (PH) and right ventricular hypertrophy (RVH) in various animal models. Depending on their net effects after blockade of endothelial and smooth muscle ET(B) receptors, nonselective ET(A/B) antagonists could be more or less effective than selective ET(A) antagonists. METHODS AND RESULTS: Two weeks after injection of saline or 60 mg/kg monocrotaline (MCT), rats received 50 mg x kg(-1) x d(-1) of a selective (LU135252) or nonselective (BSF420627) antagonist for 3 weeks. This resulted in 4 groups: control (n=15), MCT (n=60), MCT+ET(A) (n=39), and MCT+ET(A/B) (n=40). Five-week survival was 35% in the MCT group; this was increased to 56% in the MCT+ET(A) group (P:=0.10) and to 67% in the MCT+ET(A/B) group (P:=0.0015). Drug administration was stopped 48 hours before hemodynamic measurements to evaluate the chronic effects of therapy: PH in the MCT group (RV systolic pressure 87+/-1 mm Hg) was improved similarly in both MCT+ET(A) and MCT+ET(A/B) groups (72+/-3 and 70+/-3 mm Hg, respectively, P:<0.05). Severe RVH in the MCT group (RV/left ventricle+septum weight ratio 73+/-1%) was not affected by the selective antagonist (70+/-2%) but was reduced to 54+/-2% in the MCT+ET(A/B) group (P:<0.01). Pulmonary resistive properties, assessed from isolated lung pressure flow relationships, were improved similarly in survivors from both treated groups. CONCLUSIONS: Both the nonselective ET(A/B) antagonist BSF420627 and the selective ET(A) antagonist LU135252 are effective in this model of PH. Similar direct comparative studies in other models of PH and with various dosage regimens are warranted to define the optimal pharmacological approach of PH when ET receptor antagonists are used. PMID- 11208696 TI - Myocardial fibrosis in DOCA-salt hypertensive rats: effect of endothelin ET(A) receptor antagonism. AB - BACKGROUND: To test the hypothesis that endothelin-1 contributes to cardiac fibrosis, cardiac collagen deposition was studied in deoxycorticosterone acetate salt (DOCA-salt) hypertensive rats, in which the endothelin system is activated. The effects of the ET(A)-selective endothelin receptor antagonist A-127722 were evaluated. METHODS AND RESULTS: A-127722 (30 mg/kg per day) was administered for 4 weeks. Myocardial fibrosis was evaluated after Sirius red F3BA staining. Systolic blood pressure was 103+/-1.6 mm Hg in unilaterally nephrectomized rats (Uni-Nx), 202+/-3.2 mm Hg in DOCA-salt rats (P:<0.01 versus Uni-Nx), and 182+/ 3.1 mm Hg in ET(A) antagonist-treated DOCA-salt rats (P:<0.01 versus DOCA-salt or Uni-Nx). In DOCA-salt rats, interstitial and perivascular collagen density was increased in the subendocardial and midmyocardial regions of the left ventricle (3- to 4-fold, P:<0.05), whereas in subepicardial myocardium, the increase was predominantly perivascular. The ET(A) antagonist prevented cardiac fibrosis in DOCA-salt rats. Procollagen I and III mRNA, which were increased in hearts of DOCA-salt rats, were normalized by ET(A) antagonist treatment. TGF-beta(1) mRNA and TGF-beta(1) protein increased at 1 week in DOCA-salt rats and were lowered in ET(A) antagonist-treated rats. CONCLUSIONS: ET(A) receptor-mediated collagen deposition in hearts of DOCA-salt rats results from increased procollagen synthesis associated with an initial increment in expression of TGF-beta(1). These results support the hypothesis of a role for endothelin-1 in cardiac collagen deposition in mineralocorticoid hypertension, which may have pathophysiological and pharmacological implications in hypertensive heart disease. PMID- 11208697 TI - Image in cardiovascular medicine. Prenatal diagnosis of idiopathic infantile arterial calcification. PMID- 11208699 TI - Diagnostic guidelines for Kawasaki disease. PMID- 11208698 TI - Recommendations for preparticipation screening and the assessment of cardiovascular disease in masters athletes: an advisory for healthcare professionals from the working groups of the World Heart Federation, the International Federation of Sports Medicine, and the American Heart Association Committee on Exercise, Cardiac Rehabilitation, and Prevention. PMID- 11208700 TI - Mechanical cardiac support 2000: current applications and future trial design: June 15-16, 2000 Bethesda, Maryland. PMID- 11208701 TI - Images in cardiovascular medicine. Computed tomography and magnetic resonance imaging of left ventricular thrombus. PMID- 11208702 TI - Graft patency rate and clinical outcome after coronary artery bypass surgery. PMID- 11208703 TI - Beta2-adrenergic receptor overexpression exacerbates development of heart failure after aortic stenosis. PMID- 11208704 TI - Myocarditis as a cause of sudden death. PMID- 11208705 TI - Plasminogen activator inhibitor genotype and brain infarction. PMID- 11208706 TI - Cardiovascular news. PMID- 11208707 TI - Postapproval drug surveillance and the first principle of medicine. PMID- 11208708 TI - Diagnosis of specialized intestinal metaplasia by optical coherence tomography. AB - BACKGROUND AND AIMS: Optical coherence tomography (OCT) is an imaging technique that produces high-resolution cross-sectional images in vivo. The aim of this study was to establish the sensitivity and specificity of OCT for diagnosing specialized intestinal metaplasia (SIM). METHODS: OCT was used to image the stomach and esophagus of 121 patients. A total of 288 biopsy-correlated OCT images were acquired. OCT criteria for SIM were formulated by analyzing 75 images of SIM. The SIM image criteria were retrospectively tested by applying them to images of gastric, squamous, SIM, and cardiac epithelium. The criteria were then tested prospectively to determine the sensitivity and specificity of OCT for diagnosing SIM. RESULTS: OCT images of SIM are characterized by (1) absence of the layered structure of normal squamous epithelium and the vertical "pit and crypt" morphology of gastric mucosa, (2) disorganized architecture with inhomogeneous tissue contrast and an irregular mucosal surface, and (3) presence of submucosal glands. These criteria were 100% sensitive and 93% specific for SIM when applied retrospectively and 97% sensitive and 92% specific when tested prospectively. CONCLUSIONS: OCT is highly sensitive and specific for SIM and may aid in the diagnosis and surveillance of this preneoplastic lesion. PMID- 11208709 TI - Clinical, biological, and histologic parameters as predictors of relapse in ulcerative colitis. AB - BACKGROUND & AIMS: Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease. We aimed to assess whether clinical, biological, and histologic parameters in quiescent UC predict time to clinical relapse. METHODS: Seventy four patients with clinically and endoscopically determined inactive UC were followed up for 1 year or for a shorter period if they had a relapse. Serum erythrocyte sedimentation rate; C-reactive protein, interleukin (IL)-1beta, IL-6, and IL-15 values; anti-neutrophil cytoplasmic antibody titers; and rectal biopsy specimens were obtained at baseline, at 6 and 12 months, and/or at relapse. Multivariate survival analysis was performed to determine independent predictors of clinical relapse. RESULTS: Twenty-seven patients relapsed (19/42 women; 8/32 men). Multivariate Cox regression analysis retained younger age (P = 0.003; hazard ratio, 0.4 per decade), greater number of prior relapses in women (P < 0.001; hazard ratio, 1.6 per prior relapse), and basal plasmacytosis (P = 0.003; hazard ratio, 4.5) on rectal biopsy specimens as predictors of shorter time to clinical relapse. Kaplan-Meier survival curves showed the 20-30-year-old age group and women with more than 5 prior relapses to be groups with shorter times to relapse. CONCLUSIONS: Younger age, multiple previous relapses (for women), and basal plasmacytosis on rectal biopsy specimens were independent predictors of earlier relapse. These findings may help identify patients with inactive UC who will require optimal maintenance medical therapy. PMID- 11208710 TI - Efficient detection of hereditary nonpolyposis colorectal cancer gene carriers by screening for tumor microsatellite instability before germline genetic testing. AB - BACKGROUND & AIMS: The optimal strategy for the detection of hereditary nonpolyposis colorectal cancer (HNPCC) gene carriers remains uncertain. We evaluated whether microsatellite instability (MSI) analysis or MSH2 and MLH1 protein immunostaining of tumors will screen individuals efficiently for germline MSH2 and MLH1 testing. METHODS: We performed a case-series study of 114 eligible families enrolled in our high-risk colorectal cancer (CRC) registry. Medical history data were collected on probands and relatives. MSI analysis was performed on proband tumors, and MSH2 and MLH1 protein immunostaining was assessed. Denaturing gradient gel electrophoresis was used to identify germline MSH2 or MLH1 mutations in probands found to have tumors with high-frequency MSI. RESULTS: Tumor tissue and adequate clinical data were available in 109 of the 114 families. Amsterdam criteria and Bethesda guidelines were met by 23% and 70% of the families, respectively. High-frequency MSI was identified in the proband tumors in 47 of the 109 families (43%). Germline MSH2 and MLH1 gene testing was carried out in the probands of 32 of 47 families with MSI-H tumors. Mutations were detected in 16 families (9 in MSH2 and 7 in MLH1) and sequence variants of uncertain significance in 5 families (1 in MSH2 and 4 in MLH1). Germline mutations or sequence variants of uncertain significance were detected in 15 of 19 (79%) of our Amsterdam families and in 6 of 13 (46%) of our non-Amsterdam families with MSI-H tumors. MSH2 and MLH1 protein immunostaining was assessed in 38 of the 47 MSI-H tumors. Unequivocal loss of hMLH1 expression was found in 20 tumors and loss of MSH2 expression in 9 tumors. Corresponding loss of protein expression was seen in 17 of 18 (94%) of tumors from probands with germline mutations or variants. CONCLUSIONS: The detection of high-frequency MSI or the loss of MSH2 or MLH1 immunostaining in CRCs are both useful criteria for selecting high-risk patients who should be tested for germline mutations in MSH2 or MLH1. PMID- 11208711 TI - Alterations in rectal sensitivity and motility in childhood irritable bowel syndrome. AB - BACKGROUND & AIMS: Children with chronic abdominal pain have a heterogeneous clinical presentation, but no organic cause can be identified in most of them. Some children present with symptoms of irritable bowel syndrome (IBS). We hypothesized that visceral hypersensitivity and motor abnormalities may be underlying mechanisms in these children. METHODS: Rectal sensation and rectal contractile response to a meal were studied in 8 children with IBS and 8 children with functional abdominal pain (FAP) and were compared with those of 9 healthy volunteers (HVs). RESULTS: The threshold for pain, but not that for first sensation and urge to defecate, was significantly decreased in IBS patients (6 +/ 1 mm Hg) compared with FAP patients and HVs (17 +/- 1 and 22 +/- 2 mm Hg, respectively). In HVs and patients with FAP, ingestion of a meal induced a decrease in rectal volume with an early and late component. This motor pattern was absent in children with IBS. In IBS patients, no rapid volume waves were observed during fasting in contrast to FAP patients (2.7 +/- 0.3/10 min) and HVs (1.8 +/- 0.5/10 min). CONCLUSIONS: Children fulfilling the Rome II criteria for IBS have a significantly lowered threshold for pain and a disturbed contractile response to a meal. Comparable to results reported in adults, sensory and motor abnormalities might play a pathophysiologic role in childhood IBS. PMID- 11208712 TI - Tachykinins contribute to nerve-mediated contractions in the human esophagus. AB - BACKGROUND & AIMS: Tachykinins mediate nonadrenergic, noncholinergic excitation in the gastrointestinal tract, but their role in esophageal peristalsis remains unclear. METHODS: We used muscle strips from the distal third of human esophagus, obtained from patients undergoing esophagectomy for cancer, to investigate the contribution of tachykinins to nerve-mediated contractions. Isometric tension responses to agonists or electrical field stimulation were recorded in circular and longitudinal muscle strips. RESULTS: Tachykinins produced concentration dependent increases in tension in circular and longitudinal muscle strips, with the following order of potency: beta-Ala(8)-neurokinin (NK) A (4-10) > NKB > substance P, suggesting NK(2) receptor involvement. The NK(2) receptor antagonist, SR48968 (1 micromol/L), inhibited responses to tachykinins in both muscles. Nerve activation produced on- and off-contractions in circular muscle and a duration-contraction in longitudinal muscle. Atropine (10 micromol/L) insensitive nerve-evoked contractions were identified for the 3 types of responses. SR48968 produced concentration-dependent inhibition of atropine insensitive on- and off-contractions but had no effect on the duration contraction. At low stimulus frequency (1 Hz), on-contractions showed greater sensitivity to SR48968 than off-contractions. CONCLUSIONS: Nerve-mediated contractions in the human esophagus have a significant atropine-insensitive component. Tachykinins acting on NK(2) receptors can account for some, but not all, of this response, suggesting that other excitatory mechanisms also contribute. PMID- 11208713 TI - Regulated production of interferon-inducible T-cell chemoattractants by human intestinal epithelial cells. AB - BACKGROUND & AIMS: Human intestinal epithelial cells inducibly express neutrophil and monocyte chemoattractants, yet little is known about the regulated production of T-cell chemoattractants by the intestinal epithelium. IP-10, Mig, and I-TAC are 3 CXC chemokines that are known to act as CD4(+) T-cell chemoattractants. METHODS: We studied constitutive chemokine expression in human colon, and defined the regulated expression of these chemokines by reverse-transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistology using cultured human intestinal epithelial cell lines and a novel adaptation of an in vivo human intestinal xenograft model. RESULTS: IP-10 and Mig were constitutively expressed by normal human colon epithelium, and their cognate receptor, CXCR3, was expressed by mucosal mononuclear cells. Interferon (IFN)-gamma stimulation increased mRNA expression and the polarized basolateral secretion of these chemokines by human colon epithelial cell lines; infection with enteroinvasive bacteria, or stimulation with the proinflammatory cytokines tumor necrosis factor alpha and interleukin 1alpha, strongly potentiated IFN-gamma-induced epithelial cell IP-10, Mig, and I-TAC production. Epithelial cell mRNA and protein expression of IP-10, Mig, and I-TAC were rapidly up-regulated in human intestinal xenografts in response to stimulation with IFN-gamma alone or in combination with IL-1. CONCLUSIONS: The constitutive and regulated production of the IFN-gamma inducible chemokines IP-10, Mig, and I-TAC by human intestinal epithelium, and the expression of their cognate receptor, CXCR3, by mucosal mononuclear cells, suggest that the intestinal epithelium can play a role in modulating physiologic and pathologic T cell-mediated mucosal inflammation. PMID- 11208714 TI - Characterization of epithelial chemoattractants for human intestinal intraepithelial lymphocytes. AB - BACKGROUND & AIMS: Although homing of intraepithelial lymphocytes (IEL) into intestinal epithelia seems to be guided by signals from epithelia, little is known concerning functional epithelial-derived chemoattractants for IEL. METHODS: Epithelial chemoattractants for IEL were analyzed using chemotaxis chamber system, enzyme-linked immunosorbent assay, and in situ hybridization using human epithelial lines and IEL lines. RESULTS: Epithelial-conditioned media induced IEL chemotaxis, and this activity was markedly enhanced by prestimulation of epithelia with interferon-(IFN)-gamma. This chemotaxis (stimulation +) was significantly inhibited by neutralizing antibodies to IFN-gamma inducible protein 10 (IP-10) or to monokine induced by IFN-gamma (MIG). Furthermore, while high amounts of IP-10 and MIG were detected in epithelial-conditioned media after IFN gamma stimulation, equivalent concentrations of recombinant IP-10 and MIG reproduced IEL chemotaxis. Production of IP-10 and MIG in fresh epithelial cells was supported by in situ hybridization and enzyme-linked immunosorbent assay. Lastly, fresh human IEL constitutively expressed CXCR-3 (the common receptor for IP-10 and MIG), and fresh IEL also exhibited chemotaxis to by rIP-10, rMIG, and epithelial-conditioned media. CONCLUSIONS: Epithelial cells produce chemoattractants for IEL, and such chemokine production is regulated by proinflammatory cytokines such as IFN-gamma. IP-10 and MIG may serve as potentially important epithelial chemokines for IEL, especially under inflammatory conditions. PMID- 11208715 TI - Butyric acid induces apoptosis by up-regulating Bax expression via stimulation of the c-Jun N-terminal kinase/activation protein-1 pathway in human colon cancer cells. AB - BACKGROUND & AIMS: The colonic epithelial cells near the top of the crypt have been shown to undergo apoptosis. Because butyric acid (BA) is the major short chain fatty acid produced by fermentation of dietary fiber in the large bowel, it may be an important regulator of apoptosis in colorectal cancer. We investigated which signaling pathway is triggered by BA to undergo apoptosis in human colorectal cancer cells. METHODS: Human DiFi and FET colorectal cells were treated with BA to undergo apoptosis and were assayed for activation of c-Jun N terminal kinase (JNK), transcription factor activation protein 1 (AP1) and NF kappaB, and the proapoptotic molecule Bax. The contribution of specific pathways was assessed by examining the effects of dominant-negative mutants of JNK/AP1 or NF-kappaB on BA-induced Bax expression and apoptosis. RESULTS: BA-mediated DNA fragmentation and Bax induction were preceded by early stimulation of JNK, and the DNA-binding activities of AP1 and NF-kappaB. BA-induced enhancement of DNA fragmentation and stimulation of Bax promoter activity were blocked by the expression of dominant-negative mutants of JNK1 or AP1 but not NF-kappaB. CONCLUSIONS: These findings suggest that apoptosis triggered by BA involves transcriptional stimulation of the Bax gene via activation of the JNK/AP1 pathway in colonic epithelial cells. PMID- 11208716 TI - Hierarchical cleavage of focal adhesion kinase by caspases alters signal transduction during apoptosis of intestinal epithelial cells. AB - BACKGROUND & AIMS: Purified intestinal epithelial cells die of detachment-induced apoptosis due to loss of cell anchorage during isolation. Anchorage-dependent cells form focal adhesions, sites of enhanced cell-matrix attachment that confer survival signals. Focal adhesion kinase (FAK), a component of the focal adhesion signaling complex, transduces these antiapoptotic signals. In this report, the molecular events leading to cleavage of FAK by caspases during apoptosis and its functional implications are defined. METHODS: Cytosolic extracts of human intestinal epithelial cells undergoing detachment-induced apoptosis were analyzed by Western blotting, immunoprecipitation, and kinase assay. RESULTS: FAK is cleaved by the ordered proteolytic activity of 2 different members of the caspase 3 family. The first cleavage is mediated by caspase-3, generating a 94/92 kilodalton-terminal fragment, which is processed by caspase-6 to an 84-kilodalton fragment. After apoptosis is initiated, the level of FAK phosphorylation is rapidly decreased, and the phosphorylation pattern of FAK-associated proteins is dramatically modified, showing significant yet divergent changes in signal transduction. CONCLUSIONS: Cleavage of FAK during apoptosis of normal human cells is an example of the sequential, highly regulated, and coordinate action of caspases that not only dismantle a cell by proteolysis, but also alter the cell's signaling machinery. PMID- 11208717 TI - Oxidants potentiate Ca(2+)- and cAMP-stimulated Cl(-) secretion in intestinal epithelial T84 cells. AB - BACKGROUND & AIMS: Diarrhea is one of the major complications of inflammatory bowel disease. The role of oxidants in promoting net intestinal secretion is important, but the cellular mechanisms underlying their effects are unclear. We examined the effects and defined the cellular actions of the oxidant monochloramine (NH(2)Cl) on anion secretion in human colonic T84 cells. METHODS: Effects of NH(2)Cl on basal and agonist-stimulated short-circuit current (Isc) of T84 monolayers were determined. Apical Cl(-) and basolateral K(+) conductances were measured by efflux of (125)I(-) and (86)Rb(+), respectively. RESULTS: NH(2)Cl alone had little effect on Isc and (125)I(-) efflux. However, pretreatment with NH(2)Cl led to a concentration-dependent potentiation of the Ca(2+)-mediated Isc and of submaximal cAMP-mediated responses. These effects were associated with increased basolateral K(+) channel conductance and were blocked by increasing cellular Ca(2+) buffering capacity with Quin-2. Whole-cell voltage clamp experiments showed that NH(2)Cl potentiated Ca(2+) activation of basolateral K(+) channel conductance. CONCLUSIONS: Oxidants potentiate both Ca(2+)- and cAMP-stimulated Cl(-) secretion by a direct effect on calcium activated basolateral K(+) channel conductance, lowering its Ca(2+) activation threshold. This effect may play an important role in amplifying and prolonging the secretory response of inflamed intestinal mucosa and enhancing the severity of diarrhea. PMID- 11208718 TI - Interferon gamma induces enterocyte resistance against infection by the intracellular pathogen Cryptosporidium parvum. AB - BACKGROUND & AIMS: Interferon (IFN)-gamma plays an important role in the immunologic control of infection by the protozoan enteropathogen Cryptosporidium parvum. We tested the hypothesis that IFN-gamma may directly inhibit infection of enterocytes by this pathogen. METHODS: HT-29, Caco-2, and H4 human enterocyte cell lines were grown in monolayers and incubated with IFN-gamma before exposure with C. parvum. IFN-gamma receptor expression in the cell lines was determined by Western blot analysis. RESULTS: IFN-gamma inhibited C. parvum infection of both HT-29 and Caco-2 cells but not H4 cells. Response to IFN-gamma was related to the expression of the IFN-gamma receptor in the respective cell lines. The effect of IFN-gamma was partially reversed by inhibition of the JAK/STAT signaling pathway. IFN-gamma mediated its action by at least 2 mechanisms: (1) inhibition of parasite invasion and (2) by modification of intracellular Fe(2+) concentration. No role for tryptophan starvation or nitric oxide synthase activity was found. TNF-alpha and IL-1beta also had anti-C. parvum activity but had no synergistic effect with IFN-gamma. CONCLUSIONS: IFN-gamma directly induces enterocyte resistance against C. parvum infection; this observation may have important consequences for our understanding of the mucosal immune response to invasive pathogens. PMID- 11208719 TI - Epidermal growth factor receptor mediates stress-induced expression of its ligands in rat gastric epithelial cells. AB - BACKGROUND & AIMS: Epidermal growth factor (EGF)-like growth factors are induced after acute gastric injury and may play an important role in mucosal repair. However, the mechanisms that trigger these growth factors are poorly understood. We determined the role of EGF receptor (EGFR) in stress-induced expression of heparin-binding EGF-like growth factor (HB-EGF) in a rat gastric epithelial cell line (RGM1 cells). METHODS: RGM1 cells were transfected with a plasmid containing complementary DNA encoding a dominant-negative human EGFR (HERCD533). Cells were treated with hydrogen peroxide (0-400 micromol/L) or sorbitol (600 mmol/L). Tyrosine phosphorylation of EGFR was determined by immunoprecipitation and Western blotting with an antiphosphotyrosine antibody. HB-EGF messenger RNA and protein were determined with Northern and Western blotting, respectively. Cell growth was evaluated by cell number and [(3)H]thymidine incorporation. RESULTS: Oxidative stress and osmotic stress induced tyrosine phosphorylation of EGFR within 2 minutes, followed by a marked increase in HB-EGF and amphiregulin transcripts in RGM1 cells. Introduction of HERCD533 into the cells inhibited not only tyrosine phosphorylation of EGFR but also growth response to EGF. Furthermore, oxidative stress-induced HB-EGF messenger RNA expression was impaired in HERCD533-expressing cells. CONCLUSIONS: EGFR plays a crucial role in the stress-induced expression of EGF-like growth factors in gastrointestinal epithelial cells. PMID- 11208720 TI - Sucrase-isomaltase is an adenosine 3',5'-cyclic monophosphate-dependent epithelial chloride channel. AB - BACKGROUND & AIMS: We previously isolated a monoclonal antibody against a Necturus gallbladder epitope that blocks native adenosine 3',5'-cyclic monophosphate (cAMP)-dependent chloride channels in intestine, gallbladder, urinary bladder, and airway epithelia in various animals. METHODS: Using this antibody, we purified a 200-kilodalton protein that, when reconstituted in lipid bilayers, forms 9-pS chloride channels that are blocked by the antibody. RESULTS: Amino acid sequencing of the purified protein showed strong homology to rabbit sucrase-isomaltase, an abundant intestinal enzyme. Western blot analysis of the in vitro-translated sucrase-isomaltase was indistinguishable from that of the protein used in the lipid bilayer studies. Expression of this protein in Chinese hamster ovary cells and in Xenopus laevis oocytes yielded cAMP-dependent chloride currents that in the latter system were blocked by the antibody. CONCLUSIONS: Because the monoclonal antibody blocks cAMP-dependent currents in epithelia as well as those produced both by the reconstituted and by the heterologously expressed protein, sucrase-isomaltase is a cAMP-dependent epithelial chloride channel. Thus an enzyme that can also function as an ion channel has been described for the first time. PMID- 11208721 TI - Inhibition of complement C5 reduces local and remote organ injury after intestinal ischemia/reperfusion in the rat. AB - BACKGROUND & AIMS: Complement activation plays an important role in the local pathogenesis of ischemia/reperfusion (I/R) injury. We investigated the action of anti-C5 monoclonal antibody (mAb) on local and remote organ injuries after intestinal I/R in the rat. METHODS: Under anesthesia, functional anti-rat C5 mAb (18A), an isotype-matched control anti-C5 mAb (16C), or vehicle (phosphate buffered saline) was administered 60 minutes before the superior mesenteric artery was occluded for 90 minutes and reperfused for 60 minutes. Tissue injury was assessed by lactate dehydrogenase release, myeloperoxidase activity, and microvessel relaxation. Tumor necrosis factor (TNF)-alpha, interleukin (IL) 1alpha, and intercellular adhesion molecule (ICAM)-1 expression was assessed by reverse-transcription polymerase chain reaction and immunohistochemistry. RESULTS: The loss of endothelium-dependent relaxation of microvessels from the superior mesenteric artery after I/R was significantly attenuated by 18A but not by 16C. Intestinal lactate dehydrogenase release after I/R was significantly reversed by 18A treatment. Anti-C5 treatment significantly inhibited the increased myeloperoxidase activity in the lung and intestine after intestinal I/R. Furthermore, increased intestinal TNF-alpha, IL-1alpha, and vascular ICAM-1 expression after I/R were significantly inhibited by anti-C5 mAb. CONCLUSIONS: Anti-C5 therapy significantly improved intestinal I/R tissue injury as well as lung injury. PMID- 11208722 TI - Adaptive cytoprotection mediated by prostaglandin I(2) is attributable to sensitization of CRGP-containing sensory nerves. AB - BACKGROUND & AIMS: The phenomenon by which the gastric mucosa is protected in response to mild irritants has been called adaptive cytoprotection, a mechanism believed to be related to production of endogenous prostaglandins (PGs). We tested whether PGs generated by mild irritant prevent injury through the release of calcitonin gene-related peptide (CGRP) from the sensory nerves using prostanoid receptor-knockout mice. METHODS: The stomach was doubly cannulated and perfused with 1 mol/L NaCl or 50% ethanol. CGRP levels in the perfusate were determined by enzyme immunoassay, and the injured area was estimated at the end of perfusion. RESULTS: Preperfusion with mildly hypertonic saline (1 mol/L NaCl) increased generation of gastric PGE(2) and PGI(2) and reduced ethanol-induced mucosal damage. Exposure of ethanol after 1 mol/L NaCl increased intragastric CGRP levels from 166 +/- 27 to 713 +/- 55 pg/2 min (n = 4, P < 0.05), and the protective action of 1 mol/L NaCl was inhibited by indomethacin treatment. CGRP antagonist blocked 1 mol/L NaCl-induced protective effect. Intragastric perfusion of 50% ethanol after administration of PGI(2), but not of PGE(2), increased CGRP levels. Application of 1 mol/L NaCl to IP receptor-knockout mice (IP(-/-)) did not elicit the protective effects seen in the wild-type on ethanol-induced gastric mucosal lesions. Protective effect of 1 mol/L NaCl was observed in EP3 receptor-knockout mice (EP3(-/-)). CGRP level during ethanol perfusion was not increased in IP(-/-) but was increased in EP3(-/-) and wild-type counterparts after preperfusion of 1 mol/L NaCl. CONCLUSIONS: These results indicate that the endogenous PGI(2) generated by 1 mol/L NaCl may have a protective role in gastric mucosal injury through enhancement of CGRP release from gastric mucosa. This mechanism may explain the adaptive cytoprotection observed after treatment with mild irritants. PMID- 11208723 TI - Na(+)-dependent fluid absorption in intact perfused rat colonic crypts. AB - BACKGROUND & AIMS: The traditional paradigm of fluid movement in the mammalian colon is that fluid absorption and secretion are present in surface and crypt cells, respectively. We have recently demonstrated Na(+)-dependent fluid absorption in isolated crypts that are devoid of neurohumoral stimulation. We now explore the mechanism of Na(+)-dependent fluid absorption in isolated rat colonic crypts. METHODS: Net fluid absorption was determined using microperfusion techniques and methoxy[(3)H]inulin with ion substitutions and transport inhibitors. RESULTS: Net fluid absorption was reduced but not abolished by substitution of either N-methyl-D-glucamine- Cl(-) or tetramethylammonium for Na(+) and by lumen addition of 5-ethylisopropyl amiloride, an amiloride analogue that selectively inhibits Na(+)-H(+) exchange. Net fluid absorption was also dependent on lumen Cl(-) because removal of lumen Cl(-) significantly (P < 0.001) reduced net fluid absorption. DIDS at 100 micromol/L, a concentration at which DIDS is an anion exchange inhibitor, minimally reduced net fluid absorption (P < 0.05). In contrast, either 500 micromol/L DIDS, a concentration at which DIDS is known to act as a Cl(-) channel blocker, or 10 micromol/L NPPB, a Cl(-) channel blocker, both substantially inhibited net fluid absorption (P < 0.001). Finally, both the removal of bath Cl(-) and addition of bath bumetanide, an inhibitor of Na-K-2Cl cotransport and Cl(-) secretion, resulted in a significant increase in net fluid absorption. CONCLUSIONS: (1) Net Na(+)-dependent net fluid absorption in the isolated colonic crypt represents both a larger Na(+)-dependent absorptive process and a smaller secretory process; and (2) the absorptive process consists of a Na(+)-dependent, HCO(3)(-)-independent process and a Na(+)-independent, Cl( )-dependent, HCO(3)(-)-dependent process. Fluid movement in situ represents these transport processes plus fluid secretion induced by neurohumoral stimulation. PMID- 11208724 TI - Enhancement of jejunal absorption of conjugated bile acid by neurotensin in rats. AB - BACKGROUND & AIMS: Release of neurotensin (NT) from intestines is markedly stimulated by ingested fat, and NT may facilitate lipid digestion and absorption through various actions that are not fully understood. Our recent finding that NT stimulates hepatic output of bile acids only when bile delivery to the intestine is maintained has led us to investigate the effects of NT on bile acid absorption in the rat small intestine. METHODS: We measured the effects of intravenous infusion of NT (3-10 pmol x kg(-1) x min(-1)) on biliary recovery of (3)H taurocholate ((3)H-TC) and (3)H-cholate administered into proximal and distal intestines or into isolated intestinal segments in situ in biliary fistula rats. To further understand the underlying mechanisms involved, the effects of NT on intestinal absorption of (3)H-D-glucose, (3)H-leucine, (14)C-antipyrine, and (51)Cr-EDTA were investigated by monitoring the absorption of radioactivity into superior mesenteric venous blood. RESULTS: Infusion of NT, at doses that caused near physiologic increases in blood NT levels, increased biliary recovery of (3)H TC from the jejunum (3.4-fold) and ileum (1.7-fold), but did not enhance absorption of (3)H-cholate. NT also facilitated transcellular uptake of (3)H glucose and (3)H-leucine and increased paracellular uptake to (51)Cr-EDTA and (3)H-mannitol, but did not alter the absorption rate for (14)C-antipyrine. CONCLUSIONS: These results indicate that NT can exert a facilitative effect on intestinal bile acid absorption and return to liver. This effect of NT may involve increases in paracellular absorption and carrier-mediated transport by mechanisms not yet identified. PMID- 11208725 TI - Desensitization to the effects of intravenous octreotide in cirrhotic patients with portal hypertension. AB - BACKGROUND & AIMS: Octreotide has been suggested for the treatment of variceal bleeding, but detailed dose-finding studies are not available. We performed a dose-finding study investigating the hemodynamic effects of several forms of intravenous octreotide administration. METHODS: Splanchnic hemodynamics and plasma glucagon levels were measured in 68 cirrhotics in baseline conditions and (1) after a double-blind intravenous injection of octreotide (50 microg [n = 9] or 500 microg [n = 8]) or placebo (n = 7); (2) after a 50-microg octreotide bolus followed by continuous infusion of 50 microg/h (n = 8), 250 microg/h (n = 8), or placebo (n = 6); (3) after repeated 50-microg injections of octreotide (n = 9) or placebo (n = 6) after an initial bolus (50 microg octreotide); and (4) after a placebo bolus and continuous octreotide infusion (50 microg/h; n = 7). RESULTS: Placebo caused no significant changes. Octreotide caused a marked and transient decrease in portal pressure and azygos blood flow and an increase in mean arterial pressure. These effects lasted only 5 minutes despite addition of continuous octreotide infusions. Repeated octreotide injections had shorter, less marked effects than the first bolus. A continuous octreotide infusion did not decrease portal pressure. Glucagon levels were markedly reduced by octreotide, but gradually returned to baseline despite continuous infusions or repeated injections of octreotide. CONCLUSIONS: Octreotide injection caused marked but transient reductions in portal pressure and azygos blood flow. Adding a continuous octreotide infusion neither maintained nor prolonged its effects. Repeated boluses caused significant tachyphylaxis. This rapid desensitization to the effects of octreotide may explain the divergent effects achieved with octreotide infusions in acute variceal bleeding. PMID- 11208726 TI - Factors associated with poor health-related quality of life of patients with cirrhosis. AB - BACKGROUND & AIMS: Increasing interest is being given to health-related quality of life in chronic diseases. In cirrhosis, both physical functioning and mental well-being may be altered, but no study has investigated factors associated with a poor perceived health status. METHODS: We measured quality of life by Short Form-36 and Nottingham Health Profile questionnaires in 544 patients with cirrhosis. Data were compared with age- and gender-adjusted values of 2 random samples of the Italian population (more than 2000 subjects). Factors associated with poor perceived health status were identified by logistic regression. RESULTS: All domains of health-related quality of life, except pain, were altered in cirrhosis (by 9%-42%), mainly in younger patients. There were minor differences in relation to gender, whereas etiology had no effects. Severity of disease (Child-Pugh score) and, above all, muscle cramps were the factors most closely associated with poor health status perception. Self-rating of disease progression was associated with ascites and pruritus, whereas previous variceal sclerotherapy and the use of disaccharides had a protective effect. Most areas of daily life were affected by perceived health problems; this was mainly true for paid employment and sex life in men and home life and social life in women. CONCLUSIONS: Quality of life is variably impaired in cirrhosis, also in uncomplicated patients. Non-life-threatening symptoms, such as muscle cramps, are of major concern. These data are the basis for longitudinal studies measuring the effects of therapy and procedures on patient-derived health outcomes. PMID- 11208727 TI - Ethanol enhances retinoic acid metabolism into polar metabolites in rat liver via induction of cytochrome P4502E1. AB - BACKGROUND & AIMS: Long-term and excessive ethanol intake results in decreased plasma and hepatic levels of retinoic acid (RA), the most active derivative of vitamin A. The decrease of RA by ethanol treatment has been proposed to be a cytochrome P450 enzyme (CYP)-dependent process. However, the role of the major ethanol-induced CYP, CYP2E1, in the metabolism of RA has not been defined. METHODS: In vitro incubations of RA with microsomal fractions of liver tissue containing CYPs from either ethanol-exposed or non-ethanol-exposed rats were carried out using chemical inhibitors and antibodies against various CYPs. In vivo, both ethanol-exposed and non-ethanol-exposed rats were treated with or without chlormethiazole, a specific CYP2E1 inhibitor, for 1 month. RA and its catabolic metabolites were analyzed by high-performance liquid chromatography and spectral analysis. RESULTS: Incubation of RA with the liver microsomal fraction from ethanol-exposed rats resulted in greater disappearance of RA and increased appearance of 18-hydroxy-RA and 4-oxo-RA compared with control rat liver microsomal fractions. The enhancement of RA catabolism by ethanol was inhibited by both CYP2E1 antibody and specific inhibitors (allyl sulfide and chlormethiazole) in a dose-dependent fashion, whereas the metabolism of RA into polar metabolites was abolished completely by nonspecific CYP inhibitors (disulfiram and liarozole). Furthermore, treatment with chlormethiazole in ethanol-fed rats in vivo restored both hepatic and plasma RA concentrations to normal levels. CONCLUSIONS: Ethanol-induced CYP2E1 plays a major role in the degradation of RA, which may provide a possible biochemical mechanism for chronic and excessive ethanol intake as a risk for both hepatic and extrahepatic cell proliferation and carcinogenesis. PMID- 11208728 TI - Nitric oxide-mediated inhibition of DNA repair potentiates oxidative DNA damage in cholangiocytes. AB - BACKGROUND & AIMS: Chronic inflammation, a risk factor for the development of bile duct cancer, induces inducible nitric oxide synthase (iNOS) with nitric oxide (NO) generation, which promotes oxidative damage of DNA, a process that probably is important in the initiation and progression of malignancies. Because inhibition of DNA repair is required for accumulation of oxidative DNA lesions, our aim was to determine if NO also inhibits repair of oxidative DNA damage. METHODS: A cholangiocarcinoma cell line and a cholangiocyte cell line were transfected with iNOS. RESULTS: Extracts from transfected but not untransfected cells were unable to repair 8-oxodeoxyguanine (8-oxodG); this effect was irreversible because addition of dithiothreitol to cell extracts had no effect. NO inhibition of 8-oxodG repair was blocked by NO scavengers but not by peroxynitrite scavengers or inhibitors of the soluble guanylyl cyclase/protein kinase G pathway. NO also potentiated hydrogen peroxide-induced DNA damage. Finally, immunohistochemistry in human liver samples uniformly demonstrated de novo expression of iNOS and the presence of 3-nitrotyrosine and 8-oxodG formation in the biliary epithelia of 30 patients with primary sclerosing cholangitis (a premalignant disease of the biliary tract) compared with controls. CONCLUSIONS: Collectively, these data implicate NO-mediated inhibition of 8-oxodG base excision DNA repair processes as a mechanism potentiating DNA damage in human inflammatory diseases involving the biliary tract. PMID- 11208729 TI - Transcription of SST2 somatostatin receptor gene in human pancreatic cancer cells is altered by single nucleotide promoter polymorphism. AB - BACKGROUND & AIMS: The somatostatin receptor SST2 mediates the antiproliferative effect of stable somatostatin analogues. SST2 gene expression is lost in most human pancreatic carcinomas. We investigated the mechanisms that could be involved in this defect. METHODS: SST2 gene structure was investigated by sequencing and restriction fragment length polymorphism. Characterization of the polymorphism was performed by electrophoretic mobility shift, cross-linking, and transcription assays. RESULTS: No major deletion of the SST2 coding sequence was found in pancreatic carcinoma specimens, but 2 point mutations were frequently detected in the promoter sequence at positions -83 (A-->G) and -57 (C-->G) from the major transcription initiation site. These mutations were present in pancreatic cancer but also in normal pancreatic tissues or leukocytes and thus correspond to a genetic polymorphism. In the 2 human pancreatic cancer cell lines MiaPaCa-2 and AsPC-1, the naturally occurring mutation -57G had no effect on transcription of SST2 gene, whereas -83G mutation reduced it by 60%-70%. We showed that the -83G mutation creates a specific binding site for the nuclear factor I. Cotransfection experiments showed that the nuclear factor I-A1.1 isoform was responsible for SST2 promoter repression. CONCLUSIONS: The -83G polymorphism identified on human SST2 gene promoter is responsible for the specific fixation of nuclear factor I and repression of SST2 transcription in human pancreatic cancer cells. However, its contribution to pancreatic tumorigenesis remains unknown. PMID- 11208731 TI - Diffuse esophageal leiomyomatosis with perirectal involvement mimicking Hirschsprung disease. AB - We describe a 25-year-old woman with diffuse esophageal leiomyomatosis. During childhood, achalasia was mistakenly diagnosed in this patient. Subsequently, she underwent cardiomyotomy and developed symptoms of Hirschsprung disease. These symptoms were caused by infiltration of the esophageal and rectal walls by benign muscular hypertrophy. The pseudo-Hirschsprung disorder was manifested by chronic severe constipation, with consistent manometric findings. Clitoral hypertrophy and vulvar and periurethral leiomyoma were also present. Genetic analysis demonstrating deletion of the COL4A5/COL4A6 locus and the discovery of microscopic hematuria implied that the patient could transmit both diffuse leiomyomatosis and the Alport syndrome. PMID- 11208730 TI - Familial gastrointestinal stromal tumor with hyperpigmentation: association with a germline mutation of the c-kit gene. AB - We describe 2 siblings with multiple gastrointestinal stromal tumors (GISTs) and cutaneous hyperpigmentation. Both had a point mutation of the c-kit gene. The patients were sisters who had exhibited cutaneous hyperpigmentation since their late teens, but the diagnosis of multiple gastrointestinal submucosal tumors was not made until they were 41 and 45 years old. Histologic examination showed that these tumors were GISTs expressing CD34 and Kit protein. Both patients died of GISTs. Single-strand conformation polymorphism analysis showed a mutation of c kit in tumor DNA extracted from paraffin-embedded specimens. Direct sequencing analysis showed that the point mutation occurred at codon 559 of exon 11 (Val- >Ala). The same single-point mutation was detected in DNA extracted from peripheral leukocytes obtained from the younger sister and her 2 children (who had similar general hyperpigmentation) as well as in DNA from a skin biopsy specimen taken from the older sister. The germline mutation at codon 559 of the c kit gene found in the present familial GISTs differed from that in a previously reported case of familial GISTs. We propose that GISTs caused by a germline mutation of the c-kit gene should be referred to as GIST-cutaneous hyperpigmentation disease. PMID- 11208733 TI - Autoantibodies in liver disease. PMID- 11208732 TI - Chromosomal organization of candidate genes involved in cholesterol gallstone formation: a murine gallstone map. AB - Epidemiologic and family studies indicate that cholesterol gallstone formation is in part genetically determined. The major contribution to our current understanding of gallstone genes derives from animal studies, particularly cross breeding experiments in inbred mouse strains that differ in genetic susceptibility to cholesterol gallstone formation (quantitative trait loci mapping). In this review we summarize how the combined use of genomic strategies and phenotypic studies in inbred mice has proven to be a powerful means of dissecting the complex pathophysiology of this common disease. We present a "gallstone map" for the mouse, consisting of all genetic loci that have been identified to confer gallstone susceptibility as well as putative candidate genes. Translation of the genetic loci and genes between mouse and human predicts chromosomal regions in the human genome that are likely to harbor gallstone genes. Both the number and the precise understanding of gallstone genes are expected to further increase with rapid progress of the genome projects, and multiple new targets for early diagnosis and prevention of gallstone disease should become possible. PMID- 11208734 TI - Immunology of the healthy liver: old questions and new insights. PMID- 11208735 TI - American Gastroenterological Association medical position statement: nausea and vomiting. PMID- 11208736 TI - AGA technical review on nausea and vomiting. PMID- 11208737 TI - Irritable bowel syndrome in childhood. PMID- 11208738 TI - Chemokines regulate lymphocyte homing to the intestinal mucosa. PMID- 11208739 TI - Apoptosis-programmed cell death and its relevance to gastrointestinal epithelium: survival signal from the matrix. PMID- 11208740 TI - Identification of a new chloride channel: a sweet story? PMID- 11208741 TI - Octreotide and its effects on portal circulation. PMID- 11208742 TI - Chronic liver disease and health-related quality of life. PMID- 11208743 TI - Novel medical therapies for crohn's disease: is there room for growth? PMID- 11208744 TI - Management of refractory ascites: are tips or taps tops? PMID- 11208745 TI - Predicting the outcome of hepatitis C virus infection. PMID- 11208746 TI - Prokinetics reduce bacterial translocation in cirrhosis: will sweeping the gut keep the fluid clean? PMID- 11208749 TI - Effects of Blood Pressure, Smoking, and Their Interaction on Carotid Artery Structure and Function. AB - -In the present study, we examined the relationships among carotid blood pressure, arterial geometry, and wall stress and determined the impact of hypertension, smoking status, and their interaction on these relationships. The study involved 679 subjects aged 49 to 82 years: 372 smokers (190 men and 182 women) and 307 nonsmokers (110 men and 197 women). Blood samples were taken to determine total cholesterol levels. Central pulse pressure was derived from measured brachial artery pressure with a linear regression equation from data obtained in a subgroup of 276 subjects that related brachial and carotid pulse pressures; the latter was measured with applanation tonometry. Carotid intima media thickness (IMT), lumen diameter (D), and stiffness index (SI) were determined with high-resolution B-mode ultrasound. Mean and pulsatile circumferential stress (final sigma(C)) was calculated according to the Laplace relationship. Indexes of arterial geometry and function were adjusted for age, height, and heart rate. Hypertension (treated and/or screening blood pressure of >140/90 mm Hg) was present in 71 nonsmokers and 186 smokers. Nonsmokers and smokers did not differ in blood pressure and cholesterol levels. Hypertension and smoking individually and interactively significantly increased adjusted IMT, D, and SI. The radius-to-wall thickness ratio (R/IMT) (where R=D/2) and final sigma(C) were increased in hypertensives. SI was correlated with IMT (r=0.56, P:<0.001); radius-to-wall thickness ratio was inversely correlated with central pulse pressure (r=-0.38, P:<0.001). Smoking did not influence these relationships. In conclusion, carotid artery wall remodeling appears to follow Laplace's law but is insufficient to prevent an increase in circumferential stress in hypertensive subjects. Unlike hypertension, smoking does not influence the lumen-to-wall ratio but has a significant effect on wall stiffness. PMID- 11208750 TI - Baseline Characteristics and Early Blood Pressure Control in the CONVINCE Trial. AB - -Blood pressure (BP) control rates around the world are suboptimal. Part 2 of the National Health and Nutrition Educational Survey (NHANES) III indicates that only 27.4% of hypertensive Americans aged 18 to 74 years have a BP of <140/90 mm Hg. We wanted to assess BP control during the first 2 years and to describe the baseline characteristics of patients enrolled in the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) Study, an international clinical trial that compares outcomes in hypertensive patients randomized to initial treatment with either controlled-onset extended-release verapamil or the investigator's choice of atenolol or hydrochlorothiazide. At randomization, BP was <140/90 mm Hg in only 20.3% of the 16 602 subjects (average+/-SD age 65.6+/ 7.4 years; 56% women, 84% white/7% black/7% Hispanic). The average BP at enrollment was 148/85 mm Hg for patients taking BP medications (n=13 879) and 161/94 mm Hg for previously untreated patients (n=2723). After medication titration, with a transtelephonic computer that recommended an increase in the dose or number of antihypertensive agents whenever the BP was 140/90 mm Hg, 84.8% of the subjects attained the goal BP. During 2 years of treatment, BP control was maintained in 67% to 69% of the subjects (69% to 71% for systolic BP of <140 mm Hg and 90% for diastolic BP of <90 mm Hg). These data suggest that the control of systolic BP is more difficult than the control of diastolic BP. The US national goal of having 50% of hypertensives with a BP of <140/90 mm Hg may be achievable if a forced titration strategy is used. Interested investigators, free care and medications, and well-educated subjects may make the attainment of such a goal easier in the CONVINCE study than in the general population. PMID- 11208751 TI - Baseline Characteristics of Participants in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). AB - -Diuretics and ss-blockers have been shown to reduce the risk of cardiovascular morbidity and mortality in people with hypertension in long-term clinical trials. No study has compared newer more costly antihypertensive agents (calcium antagonists, ACE inhibitors, and alpha-adrenergic blockers) with diuretics for reducing the incidence of cardiovascular disease in an ethnically diverse group of middle-aged and elderly hypertensive patients. The study is a randomized, double-blind, active-controlled clinical trial designed to determine whether the incidence of the primary outcome, fatal coronary heart disease or nonfatal myocardial infarction, differs between treatment initiation with a diuretic versus each of 3 other antihypertensive drugs. Men and women aged >/=55 years with at least 1 other cardiovascular disease risk factor were randomly assigned to chlorthalidone (12.5 to 25 mg/d), amlodipine (2.5 to 10 mg/d), lisinopril (10 to 40 mg/d), or doxazosin (2 to 8 mg/d) for planned follow-up of 4 to 8 years. This report describes the baseline characteristics of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants. A total of 42 448 participants were randomized from 625 sites in the United States, Canada, Puerto Rico, and the US Virgin Islands. The mean age was 67 years, with 35% aged >/=70 years. Among those randomized, 36% were black, 19% were Hispanic, and 47% were women. The sample includes a high proportion of people with diabetes (36%), patients with existing cardiovascular disease (47%), and smokers (22%). There were no important differences between the randomized treatment groups at baseline. ALLHAT will add greatly to our understanding of the management of hypertension by providing an answer to the following question: are newer antihypertensive agents similar, superior, or inferior to traditional treatment with diuretics? PMID- 11208752 TI - Vasopeptidase Inhibition Prevents Endothelial Dysfunction of Resistance Arteries in Salt-Sensitive Hypertension in Comparison With Single ACE Inhibition. AB - -To determine whether natriuretic peptides in addition to the renin-angiotensin system are involved in functional and structural vascular changes in salt sensitive hypertension, we compared equipotent hypotensive treatment with the dual neutral endopeptidase/ACE inhibitor omapatrilat (35 mg. kg(-1). d(-1)) or the ACE inhibitor captopril (100 mg. kg(-1). d(-1)). The reactivity and geometry of mesenteric resistance arteries from Dahl salt-sensitive rats were studied in vitro under perfused and pressurized conditions. Chronic salt administration increased systolic blood pressure by 57+/-4 mm Hg, whereas concentrations of atrial natriuretic peptide were reduced in heart and in plasma (P:<0.05). In addition, the medial cross-sectional area of small mesenteric arteries was increased and endothelium-dependent relaxation in response to acetylcholine and contraction in response to endothelin-1 were impaired in the mesenteric arteries of salt-sensitive rats on a high-salt diet (P:<0.05). Concomitant treatment with either omapatrilat or captopril reduced the increase in systolic blood pressure and hypertrophic remodeling to a similar degree (P:<0.05) but affected plasma and cardiac atrial natriuretic peptide levels differently (P:<0.05). In addition, omapatrilat normalized endothelium-dependent relaxations to a greater extent than captopril (P:<0.05). Furthermore, vasopeptidase inhibition increased cGMP levels compared with captopril (P:<0.05). Contractions to endothelin-1 were normalized by either antihypertensive drug. These results suggest that in the Dahl rat, with similar reductions in systolic blood pressure, omapatrilat is superior to captopril in preventing impaired endothelial function in small resistance arteries. Thus, vasopeptidase inhibition may have therapeutic advantages of the prevention of changes in vascular function and structure in salt-sensitive forms of hypertension. PMID- 11208753 TI - Synergistic Antihypertensive Effects of Nifedipine on Endothelium : Concurrent Release of NO and Scavenging of Superoxide. AB - Recent studies have suggested that part of the vasorelaxation caused by nifedipine, a 1,4-dihydropyridine Ca(2+) antagonist, depends on the endothelium. To study the effect of endothelium-dependent vasorelaxation, the release of NO and superoxide (O(2)(-)) in the presence of nifedipine in isolated cultured rabbit endothelial cells was measured. Highly sensitive electrochemical microsensors were placed onto the cell membrane, and the kinetics of NO and O(2)( ) were measured simultaneously with time resolutions of 0.1 and 0.05 ms, respectively. Nifedipine at its therapeutical concentrations stimulated NO release and scavenged O(2)(-) in endothelial cells. The linear relationship between NO concentration and nifedipine concentration was observed in the range between 0.01 and 1 nmol/L. NO concentration reached a maximum of 200+/-10 nmol/L at 1.2 nmol/L of nifedipine. The NO concentration was approximately 50% and 30% of the concentration measured in the presence of receptor-dependent (acetylcholine) and the receptor-independent (Ca(2+) ionophore A23187) NO synthase (eNOS) agonists, respectively. NO release stimulated by eNOS agonists was followed by the generation of the NO scavenger superoxide. The concentration of O(2)(-) was significantly lower after stimulation with nifedipine (peak 5+/ 0.5 nmol/L) than after stimulation with acetylcholine (15+/-1 nmol/L) and Ca(2+) ionophore (25+/-1 nmol/L). The average rate of NO release by nifedipine is relatively slow (17 nmol/L per second). This is in sharp contrast to the fast rate of NO release by acetylcholine and Ca(2+) ionophore (40 and 300 nmol/L per second, respectively). These experiments show that nifedipine, apart from its well-known Ca(2+) antagonistic properties in vascular smooth muscle cells, stimulates the release of significant concentration of NO in endothelium and also preserves NO concentration. Both these effects may be beneficial in the treatment of hypertension. PMID- 11208754 TI - Vascular Effects of ACE Inhibition Independent of the Renin-Angiotensin System in Hypertensive Renovascular Disease : A Randomized, Double-Blind, Crossover Trial. AB - -To evaluate whether ACE inhibition and angiotensin II type 1 blockade exert beneficial effects on NO availability independent of their blood pressure lowering effect, we used a double-blind crossover design to study vascular function in 18 patients with hypertensive renovascular disease during 6 weeks of therapy with enalapril (Ena) and valsartan (Val) compared with non-renin angiotensin system-mediated treatment with the alpha(1)-blocker doxazosin (Dox). Control measurements were performed in 13 age-matched volunteers. Forearm blood flow was assessed with venous occlusion plethysmography, and serotonin and nitroprusside were used as endothelium-dependent and -independent vasodilators, respectively. Blood pressure was similar during all treatment periods. Serotonin induced vasodilation was decreased in patients during Dox treatment (n=12) compared with control subjects (n=13) (increase 42+/-20% versus 107+/-65%, P:<0.05). Crossover from Dox to Val (n=6) had no effect on serotonin response (increase 50+/-14%), but crossover to Ena (n=6) caused a significant improvement (increase 79+/-39%, P:<0.05 versus Dox). In an assessment of all patients, serotonin-induced vasodilation during Ena (n=12, increase 75+/-31%) was increased compared with both Val and Dox (43+/-14% and 42+/-20%, respectively; both P:<0.05 versus Ena). The nitroprusside response remained unaltered during all treatment periods. In conclusion, ACE inhibition improves the impaired endothelium dependent vascular function in patients with hypertensive renovascular disease. This effect is unrelated to blood pressure-lowering or angiotensin II-mediated effects. PMID- 11208755 TI - Interactive Effect of Ethnicity and ACE Insertion/Deletion Polymorphism on Vascular Reactivity. AB - -Bradykinin is a potent endothelium-dependent vasodilator that contributes to the blood pressure lowering effect of angiotensin-converting enzyme inhibition. Angiotensin-converting enzyme inhibitors are widely prescribed for the treatment of hypertension, although the efficacy of this therapy has been reported to vary among different ethnic groups. To determine whether vascular sensitivity to bradykinin is decreased in blacks compared with whites, we measured forearm blood flow with venous plethysmography in response to intraarterially-administered bradykinin (100, 200, and 400 ng/min) under salt-controlled conditions in 28 (14 black, 14 white) normotensive subjects genotyped for the ACE insertion/deletion (I:/D) polymorphism. Acetylcholine (ACh) (15, 30, and 60 ug/min) and sodium nitroprusside (SNP) (0.8, 1.6, and 3.2 ug/min) were infused as endothelium dependent and endothelium-independent controls. Compared with whites, blacks exhibited a blunted vasodilator response to bradykinin (maximal blood flow: 20.4+/-2.5 versus 10.9+/-1.4 mL. 100 mL(-1). min(-1), P:=0.004) and SNP (14.1+/ 1.6 versus 9.9+/-1.7 mL. 100 mL(-1). min(-1), P:=0.05) but not to ACh (10.5+/-2.8 versus 6.6+/-1.0 mL. 100 mL(-1). min(-1), P:=0.21). White subjects who carried at least 1 ACE D allele demonstrated significantly greater vasodilator responses to bradykinin compared with those homozygous for the I: allele (DD or I:D versus I:I, F=5.6, P:<0.04). In contrast, only blacks homozygous for the ACE D allele had a significantly greater vasodilator response to bradykinin than those who carried the I: allele (DD versus ID or II, F=8.3, P:=0.01). The ethnic difference was most pronounced in subjects heterozygous at the ACE I/D locus in which blacks had a markedly attenuated response to bradykinin compared with whites (F=41.0, P:<0.001). There was no effect of ACE I/D genotype on the vasodilator responses to SNP or ACh in either ethnic group. These data confirm that vascular reactivity to bradykinin and the endothelium-independent vasodilator SNP is decreased in normotensive blacks compared with whites, consistent with attenuated vascular smooth muscle reactivity. The data suggest that genetic variation at the ACE gene locus interacts with ethnicity to impact the vascular response to bradykinin. PMID- 11208756 TI - Hemodynamic Overload-Induced Activation of Myocardial Mitogen-Activated Protein Kinases In Vivo : Augmented Responses in Young Spontaneously Hypertensive Rats and Diminished Responses in Aged Fischer 344 Rats. AB - Mitogen-activated protein (MAP) kinases have been shown to be activated by various growth factors in cultured or isolated cardiomyocytes. However, little is known about the regulation of MAP kinases in vivo, especially in clinically important conditions, such as hypertension and senescence. In this study, we assessed mechanical overload-induced activation of myocardial MAP kinases in beating hearts from hypertensive or senescent rats. Fifteen minutes of left ventricular hemodynamic overload activated MAP kinase activity by 2.2-fold (P:<0.05) in 4-week-old Wistar-Kyoto rats. The age-matched spontaneously hypertensive rats had greater MAP kinase activity than did Wistar-Kyoto rats both at baseline (1.4 times, P:<0.05) and after the hemodynamic overload (1.7 times, P:<0.05). Myocardial MAP kinase protein level, assessed by Western blot analysis, was also higher (1.6 times, P:<0.01) in spontaneously hypertensive rats. In contrast, aged (18-month-old) Fischer 344 rats, which were known to have a diminished capacity of hypertrophy in response to mechanical stress, had lower MAP kinase activity both at baseline (63%, P:<0.01) and after the hemodynamic overload (52%, P:<0.05). Their MAP kinase protein level was lower (38%, P:<0.01) than that in young (6-month-old) adults. Alterations in MAP kinase may contribute to changes in hypertrophic response in these animals. PMID- 11208757 TI - Upregulated Expression of Rat Heart Intercellular Adhesion Molecule-1 in Angiotensin II- but Not Phenylephrine- Induced Hypertension. AB - -Intercellular adhesion molecule-1 (ICAM-1), part of an immunoglobulin-like superfamily of adhesion molecules, is involved in several cardiovascular diseases. We investigated whether in vivo angiotensin II (Ang II) increases ICAM 1 in rats. Sprague-Dawley rats were infused with vehicle or Ang II (750 ug. kg( 1). d(-1) SC) for 7 days. The contribution of Ang II receptors to ICAM-1 expression was investigated with a nonpeptide Ang II type 1 (AT(1)) receptor antagonist losartan (30 mg. kg(-1). d(-1) in drinking water). Systolic blood pressure was elevated in Ang II-treated animals compared with sham-treated controls, and losartan blocked this increase. Tumor necrosis factor (TNF)-alpha (5 ug/kg IP bolus), a prototype inducer of ICAM-1, was administered as a positive control for ICAM-1 expression. After treatment, hearts were frozen in liquid nitrogen; homogenates were subjected to SDS-PAGE and immunoblotted with an anti rat ICAM-1 monoclonal antibody. We detected a predominantly high-molecular-weight band in homogenates from non-TNF-alpha-treated rats, which was enhanced by 80+/ 5% in TNF-alpha-treated rats. This band measured approximately 200 kDa, which is the molecular weight of ICAM-1 in its native dimer form. The same band was detected in homogenates from sham and Ang II-treated rats, with the latter showing a 150+/-10% increase in ICAM-1 versus sham controls. Immunoprecipitation of rat heart homogenates with anti-rat ICAM-1 antibody resulted in a dominant band of the same molecular weight as samples not treated with antibody. Losartan prevented enhanced expression of ICAM-1 in the presence of Ang II but had no effect on basal ICAM-1 expression. Phenylephrine, an alpha-agonist (3 mg. kg(-1). d(-1) ), was infused for 1 week but had no effect on ICAM-1 expression, even though systolic blood pressure was elevated to the same level as in rats treated with Ang II. Thus, heart ICAM-1 expression is enhanced via AT(1) receptor activation independent of hypertension. Ang II-induced ICAM-1 expression was time and dose dependent, with maximal expression occurring within 5 to 7 days at 100 to 750 ug/kg Ang II. Immunohistochemical staining demonstrated markedly increased ICAM-1 levels in the perivascular area in Ang II-infused rats. Monocyte/macrophage accumulation was significantly greater in Ang II-treated rat hearts than in sham-treated hearts (10+/-1; P:<0.001; n=5). Thus during inflammation, overexpression of ICAM-1 may contribute to cardiovascular damage in diseases characterized by increased activity of the renin-angiotensin system. PMID- 11208758 TI - Rat Coronary Endothelial Cell Membrane Potential Responses During Hypertension. AB - -The purpose of this study was to provide the first membrane potential profile in coronary endothelial cells from normotensive sham-operated control and 1-kidney, 1-clip renal hypertensive rats. Dilator responses were assessed in cannulated coronary arteries from control and 1-kidney, 1-clip rats, and the perforated patch-clamp method was used to compare membrane potential responses between the intact endothelial cells. Under these conditions, acetylcholine (100 pmol/L to 10 umol/L) induced similar large dilations of coronary arteries from control and 1 kidney, 1-clip rats that were associated with endothelial cell hyperpolarizing responses of 16+/-3 and 18+/-2 mV, respectively. Substance P (10 fmol/L to 1 nmol/L) and bradykinin (100 fmol/L to 10 nmol/L) also substantially dilated coronary arteries from control rats but only induced small (2 to 4 mV) endothelial cell hyperpolarizing responses. These dilations, which appeared independent of membrane potential changes, were highly blunted or absent in arteries from 1-kidney, 1-clip rats. Thus, dilator responses to acetylcholine that are associated with large endothelial hyperpolarizing responses are normal in the small coronary arteries of 1-kidney, 1-clip rats. However, dilator response to substance P and bradykinin, which apparently are not heavily dependent on endothelial cell hyperpolarizations, are selectively targeted for impairment in the coronary arteries of this model of hypertension PMID- 11208759 TI - Angiotensin-(1-7)-Stimulated Nitric Oxide and Superoxide Release From Endothelial Cells. AB - -The stimulation of endothelium-dependent NO release by angiotensin-(1-7) [Ang-(1 7)] has been indirectly shown in terms of vasodilation, which was diminished by NO synthase inhibition or removal of the endothelium. However, direct measurement of endothelium-derived NO has not been analyzed. With a selective porphyrinic microsensor, NO release was directly assessed from single primary cultured bovine aortic endothelial cells. Ang-(1-7) caused a concentration-dependent release of NO of 1 to 10 umol/L, which was attenuated by NO synthase inhibition. [D Ala(7)]Ang-(1-7) (5 umol/L), described as a selective antagonist of Ang-(1-7) receptors, inhibited Ang-(1-7)-induced NO release only by approximately 50%, whereas preincubation of bovine aortic endothelial cells with the angiotensin II subtype 1 and 2 receptor antagonists EXP 3174 and PD 123,177 (both at 0.1 umol/L) led to an inhibition of 60% and 90%, respectively. A complete blockade of the Ang (1-7)-induced NO release was observed on preincubation of the cells with 1 umol/L concentration of the bradykinin subtype 2 receptor antagonist icatibant (HOE 140), suggesting an important role of local kinins in the action of Ang-(1-7). Simultaneous direct measurement of superoxide (O(2)(-)) detected by an O(2)(-) sensitive microsensor revealed that the moderately Ang-(1-7)-stimulated NO release was accompanied by a very slow concomitant O(2)(-) production with a relative low peak concentration in comparison to the O(2)(-) production of the strong NO releasers bradykinin and, especially, calcium ionophore. Thus, Ang-(1 7) might preserve the vascular system, among others, due to its low formation of cytotoxic peroxynitrite by the reaction between NO and O(2)(-). PMID- 11208760 TI - Systemic and Regional Hemodynamic Responses to Tempol in Angiotensin II-Infused Hypertensive Rats. AB - -Recent studies have indicated that angiotensin II (Ang II) can stimulate oxidative stress. The present study was conducted to assess the contribution of oxygen radicals to hypertension and regional circulation during Ang II-induced hypertension. With radioactive microspheres, the responses of systemic and regional hemodynamics to the membrane-permeable, metal-independent superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (tempol) were assessed in conscious Ang II-infused hypertensive rats. Ang II-infused rats (80 ng/min SC for 12 days: n=25) showed higher mean arterial pressure (MAP: 161+/-4 mm Hg) and total peripheral resistance (TPR: 1.59+/-0.08 mm Hg. min(-1). mL(-1)) than vehicle-infused normotensive rats (116+/-3 mm Hg and 0.95+/-0.04 mm Hg. min( 1). mL(-1), respectively; n=23). The blood flow rates in the brain, spleen, large intestine, and skin were significantly reduced in Ang II-infused rats compared with vehicle-infused rats, whereas rates in the lung, heart, liver, kidney, stomach, small intestine, mesenterium, skeletal muscle, and testis were similar. Vascular resistance was significantly increased in every organ studied except the lung, in which the resistance was similar. Tempol (216 umol/kg IV) significantly reduced MAP by 30+/-4% from 158+/-7 to 114+/-5 mm Hg and TPR by 35+/-6% from 1.57+/-0.17 to 0.95+/-0.04 mm Hg. min(-1). g(-1) in Ang II-infused rats (n=9) but had no effect on these parameters in vehicle-infused rats (n=8). In Ang II infused rats, tempol did not affect regional blood flow but significantly decreased vascular resistance in the brain (29+/-6%), heart (31+/-6%), liver (37+/-7%), kidney (30+/-7%), small intestine (38+/-6%), and large intestine (47+/ 7%). Ang II-infused hypertensive rats showed doubled vascular superoxide production (assessed with lucigenin chemiluminescence), which was normalized by treatment with tempol (3 mmol/L, n=7). Further studies showed that the NO synthase inhibitor, N:(omega)-nitro-L-arginine methyl ester (11 umol. kg(-1). min(-1) IV, n=11) markedly attenuated the systemic and regional hemodynamic responses of tempol in Ang II-infused rats. These results suggest that in this model of hypertension, oxidative stress may have contributed to the alterations in systemic blood pressure and regional vascular resistance through inactivation of NO. PMID- 11208761 TI - Endothelin-1-Independent and Angiotensin II-Independent Induction of Adrenomedullin Gene Expression. AB - -Adrenomedullin (AM) may function as an autocrine and/or paracrine factor in the heart, but the exact mechanisms regulating cardiac AM gene expression are unknown. The aim of the present study was to characterize the precise time course of induction of atrial and ventricular AM gene expression during pressure overload and to study whether endothelin-1 or angiotensin II plays a causal role in the activation of cardiac AM gene expression. The pressure overload was produced by arginine-vasopressin (AVP, 0.05 ug/kg per minute IV) infusion for 15 minutes, 30 minutes, 1 hour, 2 hours, or 4 hours in conscious rats. A significant increase in left ventricular AM mRNA levels was seen after 2 hours of pressure overload in the left ventricle and after 30 minutes in the left atrium. The left atrial immunoreactive AM (ir-AM) levels decreased significantly after 2 hours of pressure overload. Plasma ir-AM levels increased slightly in response to 4 hours of AVP infusion. Bolus injections of bosentan (mixed ET(A)/ET(B) receptor antagonist, 10 mg/kg IV), losartan (AT(1) receptor antagonist, 10 mg/kg IV), and their combination had no effect on the increase of cardiac AM mRNA and ir-AM levels produced by 2 hours of pressure overload. In addition, losartan, bosentan, and their combination did not affect plasma ir-AM levels in the vehicle-infused and AVP-infused animals. The present study indicates that cardiac AM gene expression is rapidly upregulated in response to pressure. The induction of ventricular and atrial AM gene expression by pressure overload is angiotensin II independent and endothelin-1-independent. PMID- 11208762 TI - Pharmacodynamic Contribution to the Vasodilator Effect of Chronic AT(1) Receptor Blockade in SHR. AB - -The present study investigated the pharmacodynamic contribution of AT(1) receptor blockade to the regional hemodynamic effects of long-term treatment with the AT(1) receptor antagonist candesartan cilexetil in adult spontaneously hypertensive rats (SHR). Blood pressure and Doppler flowmetry measurements were made during and after withdrawal of candesartan cilexetil, representing times of maximal and negligible blockade of AT(1) receptor-mediated vasoconstriction. There was marked renal, mesenteric, and hindquarter vasodilation in SHR treated for 4 weeks with candesartan cilexetil (2 mg/kg per day in drinking water, n=8) compared with vehicle (n=8). Blood pressure increased after withdrawal of candesartan cilexetil but was still reduced after 6 days, whereas regional flows and conductances did not reduce significantly compared with the last day of treatment. There was more prolonged inhibition of angiotensin (Ang) I-induced than Ang II-induced pressor responses after withdrawal of candesartan cilexetil, but these returned to control levels before blood pressure reached fully hypertensive levels. The renal and mesenteric vasoconstrictor effects of exogenously administered Ang I and Ang II returned to control levels just 2 days after withdrawal of candesartan cilexetil. Therefore, sustained inhibition of tonic Ang-mediated vasoconstriction caused by blockade of the AT(1) receptor is not the only factor contributing to the hemodynamic profile after long-term administration of candesartan cilexetil. In addition, compared with the vehicle group, blood pressures at maximum vasoconstriction and maximum vasodilation (an indirect measure of vascular hypertrophy) were significantly reduced in candesartan cilexetil-treated SHR on the last day of treatment, as was mesenteric media wall-to-lumen ratio in a separate group of similarly treated SHR. Collectively, these findings indicate that Ang-mediated vasoconstriction rapidly normalizes on withdrawal of AT(1) receptor blockade and that regression of vascular hypertrophy is important in determining blood pressure and hemodynamic status in candesartan cilexetil-treated SHR at this time. PMID- 11208764 TI - Evaluating a Model of an NRE Mediated Tissue-Specific Expression of Murine Renin Genes. AB - -We have used comparative sequence analysis to evaluate a putative silencer element that has been proposed to be involved in the differential tissue expression of the murine renin genes: Ren-1 and Ren-2. In the mouse, these genes share a similar pattern of tissue-specific renin expression. One significant difference is seen in the submandibular gland (SMG) where renin expression from the Ren-2 locus is 100-fold greater than the expression from the Ren-1 locus. One model proposes that this differential expression arises from the interplay among a negative regulatory element and a cAMP responsive element, their respective binding factors, and the disruption of the negative regulatory element by an insertion (M2) that is found in Ren-2 but not in Ren-1. The abrogation of the negative regulatory element's function as a result of the M2 insertion was proposed to be specifically responsible for the higher level of Ren-2 expression in the SMG as compared with Ren-1. We have assessed this hypothesis by looking at an allelic variant in the closely related mouse species M. hortulanus. This species shares the same high level of Ren-2 expression in the SMG as seen in other Ren-2 positive mouse strains. However, the Ren-2 M. hortulanus allele does not appear to contain the disruptive M2 element according to restriction-enzyme mapping. Our sequence analysis confirms that the M. hortulanus Ren-2 allele contains the same sequence elements present in the DBA/2 Ren-2 allele except for the M2 element. Moreover, the proposed negative regulatory element is intact at the sequence level in Ren-2 M. hortulanus allele. This analysis suggests that any involvement of the negative regulatory element in differential Ren-1 and Ren-2 expression in the SMG is not as straightforward as previously hypothesized. PMID- 11208763 TI - Thyroid Hormone Stimulates Renin Gene Expression Through the Thyroid Hormone Response Element. AB - -We previously reported that thyroid hormone stimulates renin synthesis in vivo and in vitro. Here, we analyzed the 5'-flanking sequence of the human renin gene for promoter activity responsive to thyroid hormone using Calu-6 cells, which secrete renin endogenously and express thyroid hormone receptor-ss. The luciferase reporter gene was cloned together with 5'-flanking portions of the human renin gene of various lengths into the pGL3-Basic vector. Luciferase activity assays were performed using the Dual Luciferase Reporter Assay System. 3,3',5-Triiodo-L-thyronine stimulated the promoter activity of pGL3-Basic 1111/+12 and pGL3-Basic-1298/+12 by 2.3+/-0.1- and 1.7+/-0.1-fold, respectively. Shorter constructs (pGL3-Basic-144/+12, pGL3-Basic-226/+12, pGL3-Basic-452/+12, and pGL3-Basic-953/+12) were not stimulated by thyroid hormone. These results suggest that there is a possible thyroid hormone response element (5'-AGG TCA GGT CAc aat GTT CCT-3') between nucleotides -1111 and -953. In 3 constructs with site directed mutations in this sequence, basal promoter activities were significantly increased, whereas promoter activation by thyroid hormone was abolished. Electrophoretic mobility shift assays showed that the -1111/-953 DNA fragment of the intact human renin gene was bound to nuclear proteins of Calu-6 cells; however, none of the 3 mutant probes were bound to any nuclear proteins. These results suggest that thyroid hormone stimulates the promoter activity of the human renin gene through thyroid hormone response element-dependent mechanisms in Calu-6 cells. PMID- 11208765 TI - Differential Distribution of Bradykinin B(2) Receptors in the Rat and Human Cardiovascular System. AB - -Bradykinin, a major vasodilator peptide, plays an important role in the local regulation of blood pressure, blood flow, and vascular permeability; however, the cellular distribution of the major bradykinin B(2) receptor in the cardiovascular system is not precisely known. Immunoblot analysis with an anti-peptide antibody to the bradykinin B(2) receptor or chemical cross-linkage with [(125)I]Tyr(0) bradykinin revealed a band of 69+/-3 kDa at varying intensity in the homogenates of the endothelium and tunica media of the rat aorta and endocardium. Immunostaining showed that the B(2) receptor is abundant in the endothelial linings of the aorta, other elastic arteries, muscular arteries, capillaries, venules, and large veins, where it localizes preferentially to the luminal face of the endothelial cells. In marked contrast, small arterioles (ie, the principal blood-pressure regulating vessels) of the mesenterium, heart, urinary bladder, brain, salivary gland, and kidney had a different staining pattern in which B(2) receptor was prominent in the perivascular smooth muscle cells of the tunica media. A similar distribution pattern was found in mouse as well as in human tissues, indicating that the particular distribution pattern of the B(2) receptor in arterioles is not a species-specific phenomenon. During development, the distribution of B(2) receptor in the heart changes; for example, in the heart of newborn rats, the B(2) receptor was abundant in the myocardium, whereas in the adult heart, the receptor was present in the endocardium of atria, atrioventricular valves, and ventricles but not in the myocardium. Thus, B(2) receptors are localized differentially in different parts of the cardiovascular system: the arterioles have smooth muscle-localized B(2) receptors, and large elastic vessels have endothelium-localized receptors. PMID- 11208766 TI - Effect of Chronic Blockade of the Kallikrein-Kinin System on the Development of Hypertension in Rats. AB - -The kallikrein-kininogen-kinin system is an important vasodilator and vasodepressor component of the cardiovascular system. Acting mainly through B(2) receptors, kinins may counterbalance the pressor effect of angiotensin II, salt, and mineralocorticoids plus salt. Using rats lacking the bradykinin precursors low- and high-molecular-weight kininogen or a B(2) kinin receptor antagonist (icatibant), we investigated whether absence or blockade of the kallikrein-kinin system alters blood pressure (BP) in rats given (1) chronic infusion of Ang II, (2) a normal or high salt diet, or (3) chronic administration of deoxycorticosterone acetate (DOCA) plus salt. We confirmed the genotype and phenotype of Brown Norway Katholiek rats (BNK) and found that they had a G-to-A point mutation on the kininogen gene compared with Brown Norway (BN) and Sprague Dawley (SD) rats, very low levels of high-molecular-weight kininogen (17+/-3 ng/mL) compared with BN and SD (1814+/-253 and 2397+/-302 ng/mL, respectively; P:<0.01), and plasma low-molecular-weight kininogen concentrations below detectable limits compared with 1773+/-74 and 1781+/-140 ng/mL for BN and SD, respectively. Basal BP was the same in BNK and BN. Chronic infusion of icatibant did not alter BP in BN or Wistar rats. At doses that blocked the acute effect of bradykinin, icatibant did not potentiate the pressor effect of a chronic subpressor or pressor dose of angiotensin II in male and female Wistar rats nor that of a high salt diet (2%) plus unilateral nephrectomy in male Wistar rats. Moreover, blockade of the kallikrein-kininogen-kinin system in either BN rats given a very high dose of icatibant or kinin-deficient rats (BNK) did not potentiate the pressor effect of angiotensin II (nonpressor dose) or a high salt (3% NaCl) diet given for 2 weeks. Established DOCA-salt hypertension was not exaggerated in rats treated with icatibant but was partially attenuated by ramipril (1.5 mg. kg(-)(1). d(-)(1) for 7 days; P:<0.002). This antihypertensive effect was abolished by icatibant (P:<0.002, ramipril versus ramipril plus icatibant). These results suggest that endogenous kinins do not participate in the maintenance of normal blood pressure or antagonize the development of hypertension induced by chronic infusion of angiotensin II, a high salt diet, or DOCA-salt. However, kinins appear to play an important role in the antihypertensive effect of angiotensin-converting enzyme inhibitors in DOCA-salt hypertension. PMID- 11208767 TI - Role of Cyclooxygenase-2-Derived Metabolites and NO in Renal Response to Bradykinin. AB - -It has been reported that bradykinin (BK) can induce or activate both cyclooxygenase (COX) isoforms and that the renal effects of BK seem to be mediated by prostaglandins and NO. The first objective of this study was to evaluate the relative contribution of both COX isoforms in mediating the renal response to BK in anesthetized dogs. The second objective was to examine whether COX-2 inhibition potentiates the renal effects induced by NO reduction during BK administration. Intrarenal BK infusion (8 ng. kg(-1). min(-1), n=6) elicited a significant increment in renal blood flow, sodium excretion, urine volume, and the fractional excretion of lithium. COX-2 inhibition (nimesulide, 5 ug. kg(-1). min(-1), n=6) reduced the renal vasodilatation but did not significantly modify the natriuresis or diuresis secondary to BK. Administration of a nonspecific isozyme COX inhibitor (meclofenamate, 5 ug. kg(-1). min(-1); n=6) did not induce greater effects than those produced by nimesulide. NO synthesis reduction (N:(G) nitro-L-arginine methyl ester [L-NAME], 3 ug. kg(-1). min(-1)) prevented the renal vasodilatation and the increment in the fractional excretion of lithium induced by BK but did not affect the natriuretic or diuretic response. Simultaneous nimesulide infusion did not modify the renal effects of L-NAME during BK infusion (n=6). Finally, inhibition of both COX isoforms with meclofenamate, in dogs treated with L-NAME (n=6), completely prevented the vasodilator and excretory actions of BK. The results of this study suggest that (1) NO and prostanoids dependent on COX-2 seem to be involved in the renal vasodilatation induced by BK, and (2) there is an interaction between NO and COX 1-derived metabolites in mediating the natriuretic and diuretic response to BK. PMID- 11208768 TI - Expression of Ca(2+) Transport Genes in Platelets and Endothelial Cells in Hypertension. AB - -Altered Ca(2+) handling is observed in different cells in essential hypertension. We investigated the expression of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) and inositol 1,4,5-trisphosphate receptor (IP(3)R) isoforms in platelets and aortic endothelial cells (EC) isolated from spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats by ratio reverse-transcriptase polymerase chain reaction (RT-PCR) analysis and Western blotting. SERCA2b and SERCA3 were assessed at mRNA (EC and platelets) and at protein level (platelets). IP(3)R1, IP(3)R2, and IP(3)R3 mRNAs were demonstrated in both cell types, but only IP(3)R1 and IP(3)R2 proteins were detected in platelets. Compared with WKY, SHR EC and platelets showed higher SERCA3 and IP(3)R2 expression and lower IP(3)R1 expression. We then investigated the effect of lisinopril (20 mg. kg( )(1). d(-)(1); 10-week treatment of 4-week-old rats or 2-week treatment of adult rats) and captopril (100 mg. kg(-)(1). d(-)(1); 2-week treatment of adult rats). Consequently, expression patterns of SERCAs and IP(3)Rs were significantly modified. Except for SERCAs mRNA in platelets, all differences between SHR and WKY disappeared. However, SERCA3 remained the predominant isoform. Both EC and platelets demonstrated a high equal expression of IP(3)R2 mRNA. IP(3)R1 was the predominant platelet protein isoform, as it was in untreated WKY. mRNA was also isolated from pancreatic islets of WKY and SHR, but no effect of either rat strain or of lisinopril treatment was observed on the expression of the studied genes. We hypothesize that the identical expression pattern of SERCAs and IP(3)Rs after treatment with ACE inhibitors represents a different nonhypertensive configuration, which, through changes in intracellular Ca(2+) handling, improves endothelial and platelet dysfunction in SHR but has no effect in WKY. PMID- 11208769 TI - Vascular Effects of Progesterone : Role of Cellular Calcium Regulation. AB - -Vascular actions of progesterone have been reported, independently of estrogen, affecting both blood pressure and other aspects of the cardiovascular system. To study possible mechanisms underlying these effects, we examined the effects of P in vivo in intact rats and in vitro in isolated artery and vascular smooth muscle cell preparations. In anesthetized Sprague-Dawley rats, bolus intravenous injections of P (100 ug/kg) significantly decreased pressor responses to norepinephrine (0.3 ug/kg). In vitro, progesterone (10(-8) to 10(-5) mmol/L) produced a significant, dose-dependent relaxation of isolated helical strips, both of rat tail artery precontracted with KCl (60 mmol/L) or arginine vasopressin (3 nmol/L), and of rat aorta precontracted with KCl (60 mmol/L) or norepinephrine (0.1 umol/L). In isolated vascular smooth muscle cells, progesterone (5x10(-)(7) mol/L) reversibly inhibited KCl (30 mmol/L) -induced elevation of cytosolic-free calcium by 64.1+/-5.5% (P:<0.05), and in whole-cell patch-clamp experiments, progesterone (5x10(-6) mol/L) reversibly and significantly blunted L-type calcium channel inward current, decreasing peak inward current to 65.7+/-4.3% of the control value (P:<0.05). Our results provide evidence that progesterone is a vasoactive hormone, inhibiting agonist-induced vasoconstriction. The data further suggest that progesterone effects on vascular tissue may, at least in part, be mediated by modulation of the L-type calcium channel current activity and, consequently, of cytosolic-free calcium content. PMID- 11208770 TI - Salicylate Inhibits Phosphorylation of the Nonreceptor Tyrosine Kinases, Proline Rich Tyrosine Kinase 2 and c-Src. AB - -The anti-inflammatory effects of salicylate are well known, but the intracellular mechanisms underlying those effects remain to be clarified and are not explained solely by an influence on cyclooxygenase activity. In the present study, we have used cardiac fibroblasts stimulated by either angiotensin II (Ang II) or platelet-derived growth factor (PDGF) to demonstrate an inhibitory effect of salicylate on the phosphorylation of the nonreceptor tyrosine kinases, proline rich tyrosine kinase 2 (PYK2) and c-Src, by immunoprecipitation and immunoblotting methods. This inhibition was dose dependent, with a clear effect observed at concentrations between 5 and 20 mmol/L salicylate. Intracellular Ca(2+) chelation and protein kinase C (PKC) inhibition reduced Ang II and PDGF induced PYK2 and c-Src phosphorylation. Salicylate significantly inhibited the phosphorylation of both of the tyrosine kinases activated by either ionophore A23187 or thapsigargin treatment, which led to an elevation of cytosolic Ca(2+). Activation of PKC by phorbol ester phosphorylated both PYK2 and Src, and this effect also was attenuated by salicylate. In contrast, salicylate had no effect on either the transactivation of the epidermal growth factor receptor by Ang II or the phosphorylation of phospholipase C-gamma by PDGF. These studies indicate a novel site of action for salicylate on PYK2 and c-Src phosphorylation and suggest that this inhibitory effect on these important signaling intermediates may be through a Ca(2+)- and PKC-dependent mechanism. PMID- 11208771 TI - Antibodies to Lysophosphatidylcholine Are Decreased in Borderline Hypertension. AB - -Atherosclerosis is characterized by infiltration in the lesions of cytokine producing T cells and macrophages, where oxidized LDL may play an important role. However, little is known about the role of the immune system in the development of hypertension. Lysophosphatidylcholine (LPC) is formed by phospholipase A(2) induced hydrolysis and/or by oxidation of LDL and other phospholipid-containing membranes. The objective of the present study was to investigate the role of antibodies to LPC in borderline hypertension (BHT). Seventy-five men with BHT were compared with 75 age-matched normotensive (NT) men (diastolic blood pressure 85 to 94 and <80 mm Hg, respectively). Antibody levels to LPC of IgM and IgG isotypes and IgG subclasses were determined with ELISAs. BHT men had significantly lower anti-LPC antibody levels of both IgG class (P:=0.0002) and IgM class (P:=0.0003) than did NT controls. Subclass analysis indicated that IgG(1) (P:=0.0005), but not IgG(2), was decreased. Anti-LPC antibodies or immunoglobulin subclasses thereof were negatively associated with atherosclerosis on the basis of intima-media thickness (P:=0.02), metabolic factors (P:=0.02), smoking (P:=0.02), and endothelin (P:=0.03). LPC has proinflammatory properties and is toxic at higher concentrations and thus may play a role in atherogenesis. Furthermore, LPC functions as a vasoconstrictor in experimental systems by inhibiting NO-mediated vasorelaxation. An intriguing possibility is that anti-LPC antibodies counteract these effects. Taken together, our data indicate that anti LPC antibodies may constitute a novel factor in the development of hypertension and atherosclerosis. PMID- 11208772 TI - Fluid Shear Stress Reduces 11ss-Hydroxysteroid Dehydrogenase Type 2. AB - -In pregnancy, invading trophoblasts represent the inner vascular border of maternal spiral arteries and are exposed to elevated shear stress (ss) in hypertensive disorders. Intracellular cortisol availability is regulated by 11ss hydroxysteroid dehydrogenases (11ss-HSDs), thus determining body fluid volume and vascular responses. The impact of ss on 11ss-HSD2 activity was studied in the human JEG-3 cell line, a model for trophoblasts. JEG-3 cells do not express 11ss HSD1; however, 11ss-HSD2 message and activity are measured via cortisol/cortisone conversion in cell lysates, and both are reduced by ss. The reduction in 11ss HSD2 activity via ss is dose dependent and completely reversible after the discontinuation of ss. cAMP-dependent protein kinase A activation increased the 11ss-HSD2 activity yet did not prevent the ss response. The ss response was completely protein kinase C independent. The mitogen-activated protein kinase kinase inhibitor PD-098059 enhanced 11ss-HSD2 activity in static conditions yet only ameliorated the ss effect. Cytochalasin D disrupts focal adhesion (FA) cytoskeleton interactions and abolished the ss-induced tyrosine phosphorylation of FA kinase dose-dependently, thus maintaining 11ss-HSD2 activity. The 11ss-HSD2 activity was only partially restored by the tyrosine kinase inhibitor genistein; however, herbimycin A almost completely abolished the ss effect on 11ss-HSD2 activity. In conclusion, JEG-3 cells express 11ss-HSD2, which is downregulated by ss. Regulatory mechanisms involve transcriptional control and require intact FA cytoskeleton signaling and phosphorylation of FA kinase. Thus, ss adds to an enhanced intracellular availability of cortisol, which may ultimately support a vasoconstrictive vascular response. PMID- 11208773 TI - Mycophenolate Mofetil Reduces Renal Injury in the Chronic Nitric Oxide Synthase Inhibition Model. AB - -We and others have recently shown that mycophenolate mofetil (MMF) reduces renal inflammation and glomerular and interstitial injury in the 5/6 renal ablation model. In the present study, we investigated whether MMF limits renal injury in a model of chronic nitric oxide (NO) inhibition associated with a high-salt diet and characterized by progressive systemic hypertension, albuminuria, glomerular sclerosis and ischemia, interstitial expansion, and progressive macrophage infiltration. Adult male Munich-Wistar rats were distributed among 3 groups: HS, rats receiving a high-salt diet (3.2% Na); HS+N, HS rats orally treated with the NO inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME), 25 mg. kg(-1). d( 1); and HS+N+MMF, HS+N rats orally treated with MMF, 10 mg. kg(-1). d(-1). Renal hemodynamics were studied after 15 days of treatment; histological and immunohistochemical studies were conducted after 30 days of treatment. MMF treatment did not reverse the hemodynamic alterations characteristic of this model. Renal injury in the HS+N group was associated with macrophage and lymphocyte infiltration. Treatment with MMF reduced glomerular and interstitial injury and limited macrophage and lymphocyte infiltration. These results suggest that renal inflammation is a strong independent factor in the pathogenesis of the nephropathy associated with the HS+N model. PMID- 11208775 TI - Are Angiotensin II Receptor Antagonists Safe in Patients With Previous Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema? PMID- 11208774 TI - Neurovascular Contact of Cranial Nerve IX and X Root-Entry Zone in Hypertensive Patients. AB - -Neurovascular contact of the left rostral ventrolateral medulla has been implicated in the pathogenesis of "essential" hypertension, and recent intervention studies suggest that surgical decompression of the ventrolateral medulla lowers blood pressure in these patients. We assessed the prevalence of this vascular anomaly in patients with essential hypertension by using an advanced MRI technique. We performed MRI of the brain stem in 125 hypertensive patients and in 105 age-matched, sex-matched, and body mass index-matched normotensive control subjects. Imaging of the root-entry zone of cranial nerves IX and X was performed by combining a high-resolution 3D constructive interference in steady-state sequence with a flow-sensitive time-of-flight technique, and images were independently assessed by 4 readers using predefined criteria. Left-sided neurovascular contact was found in 23% of the hypertensive patients and in 16% of the normotensive individuals (P:=0.12). Blood pressure level, heart rate, and number of antihypertensive medications in treated hypertensive patients were similar among patients with positive, borderline, and negative brain stem findings. Our findings cast doubt on the importance of left sided neurovascular contact as a frequent cause of essential hypertension or as a major factor determining the severity of hypertension in patients with this anomaly. PMID- 11208776 TI - MexR repressor of the mexAB-oprM multidrug efflux operon of Pseudomonas aeruginosa: identification of MexR binding sites in the mexA-mexR intergenic region. AB - The MexR repressor of the mexAB-oprM multidrug efflux operon of Pseudomonas aeruginosa was purified as a C-terminal histidine-tagged protein by metal chelate affinity chromatography. The purified protein was shown to bind ca. 200 bp upstream of mexA, at two sites, each of which contains a repeat of the nucleotide sequence GTTGA in inverse orientation. DNA sequence analysis identified mexA and mexR promoters within the MexR binding regions, consistent with the previously observed negative regulation of mexR and mexAB-oprM expression by MexR. Transcription of mexA from the promoter originating within the MexR binding site II was confirmed and shown to be markedly enhanced in a nalB (i.e., mexR) mutant of P. aeruginosa. A second mexA promoter was also identified, ca. 70 bp upstream of mexAB-oprM, and transcription from this promoter appeared to occur in both the wild type and a nalB mutant. Production of MexAB-OprM in wild-type cells may be due to expression from a constitutively expressed proximal promoter, while MexAB OprM hyperexpression in nalB mutants is due to the additional expression from a MexR-regulated distal promoter. PMID- 11208778 TI - Hyperactive glycogen synthase mutants of Saccharomyces cerevisiae suppress the glc7-1 protein phosphatase mutant. AB - A yeast glc7-1 mutant expressing a variant of protein phosphatase type 1 fails to accumulate glycogen. This defect is associated with hyperphosphorylated and inactive glycogen synthase, consistent with Glc7p acting directly to dephosphorylate and activate glycogen synthase. To characterize the glycogen synthesis defect of this mutant in more detail, we isolated 26 pseudorevertants of the glc7-1 mutant. All pseudoreversion events were due to missense mutations in GSY2, the gene encoding the major isoform of glycogen synthase. A majority of the mutations responsible for the suppression were in the 3' end of the gene, corresponding to the phosphorylated COOH terminus of Gsy2p. Phosphorylation of the mutant proteins was reduced, suggesting that they are poor substrates for glycogen synthase kinases. Suppressor mutations outside this domain did not decrease the phosphorylation of the resulting proteins, indicating that these proteins are immune to the regulatory effects of phosphorylation. Since no growth defect has been observed for strains with altered glycogen levels, the relative levels of fitness of GSY2 mutants that fail to accumulate glycogen and that hyperaccumulate glycogen were assayed by cocultivation experiments. A wild-type strain outcompeted both hypo- and hyperaccumulating strains, suggesting that glycogen levels contribute substantially to the fitness of yeast. PMID- 11208777 TI - Essential PchG-dependent reduction in pyochelin biosynthesis of Pseudomonas aeruginosa. AB - The biosynthetic genes pchDCBA and pchEF, which are known to be required for the formation of the siderophore pyochelin and its precursors salicylate and dihydroaeruginoate (Dha), are clustered with the pchR regulatory gene on the chromosome of Pseudomonas aeruginosa. The 4.6-kb region located downstream of the pchEF genes was found to contain three additional, contiguous genes, pchG, pchH, and pchI, probably forming a pchEFGHI operon. The deduced amino acid sequences of PchH and PchI are similar to those of ATP binding cassette transport proteins with an export function. PchG is a homolog of the Yersinia pestis and Y. enterocolitica proteins YbtU and Irp3, which are involved in the biosynthesis of yersiniabactin. A null mutation in pchG abolished pyochelin formation, whereas mutations in pchH and pchI did not affect the amounts of salicylate, Dha, and pyochelin produced. The pyochelin biosynthetic genes were expressed from a vector promoter, uncoupling them from Fur-mediated repression by iron and PchR-dependent induction by pyochelin. In a P. aeruginosa mutant lacking the entire pyochelin biosynthetic gene cluster, the expressed pchDCBA and pchEFG genes were sufficient for salicylate, Dha, and pyochelin production. Pyochelin formation was also obtained in the heterologous host Escherichia coli expressing pchDCBA and pchEFG together with the E. coli entD gene, which provides a phosphopantetheinyl transferase necessary for PchE and PchF activation. The PchG protein was purified and used in combination with PchD and phosphopantetheinylated PchE and PchF in vitro to produce pyochelin from salicylate, L-cysteine, ATP, NADPH, and S adenosylmethionine. Based on this assay, a reductase function was attributed to PchG. In summary, this study completes the identification of the biosynthetic genes required for pyochelin formation from chorismate in P. aeruginosa. PMID- 11208779 TI - Identification of a UPC2 homolog in Saccharomyces cerevisiae and its involvement in aerobic sterol uptake. AB - Saccharomyces cerevisiae normally will not take up sterols from the environment under aerobic conditions. A specific mutant, upc2-1, of the predicted transcriptional activator UPC2 (YDR213w) has been recognized as a strain that allows a high level of aerobic sterol uptake. Another predicted transcriptional activator, the YLR228c gene product, is highly homologous to Upc2p. In fact, at the carboxy terminus 130 of the last 139 amino acids are similar between the two proteins. Since these proteins are very similar, the effect of mutations in the YLR228c open reading frame (ORF) was compared with like alterations in UPC2. First, the YLR228c ORF was insertionally inactivated and crossed with various UPC2 constructs. Deletion of YLR228c and UPC2 in combination resulted in nonviability, suggesting that the two proteins have some essential overlapping function. The upc2-1 point mutation responsible for aerobic sterol uptake was duplicated in the homologous carboxy region of the YLR228c ORF using site directed mutagenesis. This mutation on a high-copy vector resulted in an increase in sterol uptake compared to an isogenic wild-type strain. The combination of both point mutations resulted in the greatest level of aerobic sterol uptake. When the YLR228c point mutation was expressed from a low-copy vector there was little if any effect on sterol uptake. Gas chromatographic analysis of the nonsaponifiable fractions of the various strains showed that the major sterol for all YLR228c and UPC2 combinations was ergosterol, the consensus yeast sterol. PMID- 11208781 TI - Identification of a genomic island present in the majority of pathogenic isolates of Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa, a ubiquitous gram-negative bacterium, is capable of colonizing a wide range of environmental niches and can also cause serious infections in humans. In order to understand the genetic makeup of pathogenic P. aeruginosa strains, a method of differential hybridization of arrayed libraries of cloned DNA fragments was developed. An M13 library of DNA from strain X24509, isolated from a patient with a urinary tract infection, was screened using a DNA probe from P. aeruginosa strain PAO1. The genome of PAO1 has been recently sequenced and can be used as a reference for comparisons of genetic organization in different strains. M13 clones that did not react with a DNA probe from PAO1 carried X24509-specific inserts. When a similar array hybridization analysis with DNA probes from different strains was used, a set of M13 clones which carried sequences present in the majority of human P. aeruginosa isolates from a wide range of clinical sources was identified. The inserts of these clones were used to identify cosmids encompassing a contiguous 48.9-kb region of the X24509 chromosome called PAGI-1 (for "P. aeruginosa genomic island 1"). PAGI-1 is incorporated in the X24509 chromosome at a locus that shows a deletion of a 6,729 bp region present in strain PAO1. Survey of the incidence of PAGI-1 revealed that this island is present in 85% of the strains from clinical sources. Approximately half of the PAGI-1-carrying strains show the same deletion as X24509, while the remaining strains contain both the PAGI-1 sequences and the 6,729-bp PAO1 segment. Sequence analysis of PAGI-1 revealed that it contains 51 predicted open reading frames. Several of these genes encoded products with predictable function based on their sequence similarities to known genes, including insertion sequences, determinants of regulatory proteins, a number of dehydrogenase gene homologs, and two for proteins of implicated in detoxification of reactive oxygen species. It is very likely that PAGI-1 was acquired by a large number of P. aeruginosa isolates through horizontal gene transfer. The selection for its maintenance may be the consequence of expression of any one of the genes of unknown function or the genes which allow P. aeruginosa to survive under the conditions that generate reactive oxygen species. Alternatively, one or both of the transcriptional regulators encoded in PAGI-1 may control the expression of genes in the P. aeruginosa chromosome, which provides a selective advantage for strains that have acquired this genomic island. PMID- 11208780 TI - Two-component sensor required for normal symbiotic colonization of euprymna scolopes by Vibrio fischeri. AB - The light organ of the squid Euprymna scolopes is specifically colonized to a high density by the marine bacterium Vibrio fischeri. To date, only a few factors contributing to the specificity of this symbiosis have been identified. Using a genetic screen for random transposon mutants defective in initiating the symbiotic association or in colonizing the light organ to high density, we identified a mutant of V. fischeri that exhibited an apparent defect in symbiosis initiation. This mutant was not defective in motility, luminescence, or growth in minimal medium, suggesting that it lacks an essential, previously unidentified symbiotic function. By sequence analysis, we showed that the locus inactivated in this mutant encodes a predicted 927-amino-acid protein with a high degree of similarity to the sensor component of hybrid two-component regulatory systems. We have therefore designated this locus rscS, for regulator of symbiotic colonization-sensor. Sequence analysis revealed two hydrophobic regions which may result in the formation of a periplasmic loop involved in signal recognition; PhoA fusion data supported this proposed membrane topology. We have investigated the start site of rscS transcription by primer extension and identified a putative promoter region. We hypothesize that RscS recognizes a signal associated with the light organ environment and responds by stimulating a putative response regulator that controls protein function or gene expression to coordinate early colonization events. Further studies on RscS, its cognate response regulator, and the signaling conditions will provide important insight into the interaction between V. fischeri and E. scolopes. PMID- 11208783 TI - Infrequent genetic exchange and recombination in the mitochondrial genome of Candida albicans. AB - Previous analyses of diploid nuclear genotypes have concluded that recombination has occurred in populations of the yeast Candida albicans. To address the possibilities of clonality and recombination in an effectively haploid genome, we sequenced seven regions of mitochondrial DNA (mtDNA) in 45 strains of C. albicans from human immunodeficiency virus-positive patients in Toronto, Canada, and 3 standard reference isolates of C. albicans, CA, CAI4, and WO-1. Among a total of 2,553 nucleotides in the seven regions, 62 polymorphic nucleotide sites and seven indels defined nine distinct mtDNA haplotypes among the 48 strains. Five of these haplotypes occurred in more than one strain, indicating clonal proliferation of mtDNA. Phylogenetic analysis of mtDNA haplotypes resulted in one most parsimonious tree. Most of the nucleotide sites undergoing parallel change in this tree were clustered in blocks that corresponded to sequenced regions. Because of the existence of these blocks, the apparent homoplasy can be attributed to infrequent, past genetic exchange and recombination between individuals and cannot be attributed to parallel mutation. Among strains sharing the same mtDNA haplotypes, multilocus nuclear genotypes were more similar than expected from a random comparison of nuclear DNA genotypes, suggesting that clonal proliferation of the mitochondrial genome was accompanied by clonal proliferation of the nuclear genome. PMID- 11208782 TI - Enhanced symbiotic performance by Rhizobium tropici glycogen synthase mutants. AB - We isolated a Tn5-induced Rhizobium tropici mutant that has enhanced capacity to oxidize N,N-dimethyl-p-phenylendiamine (DMPD) and therefore has enhanced respiration via cytochrome oxidase. The mutant had increased levels of the cytochromes c(1) and CycM and a small increase in the amount of cytochrome aa(3). In plant tests, the mutant increased the dry weight of Phaseolus vulgaris plants by 20 to 38% compared with the control strain, thus showing significantly enhanced symbiotic performance. The predicted product of the mutated gene is homologous to glycogen synthases from several bacteria, and the mutant lacked glycogen. The DNA sequence of the adjacent gene region revealed six genes predicted to encode products homologous to the following gene products from Escherichia coli: glycogen phosphorylase (glgP), glycogen branching enzyme (glgB), ADP glucose pyrophosphorylase (glgC), glycogen synthase (glgA), phosphoglucomutase (pgm), and glycogen debranching enzyme (glgX). All six genes are transcribed in the same direction, and analysis with lacZ gene fusions suggests that the first five genes are organized in one operon, although pgm appears to have an additional promoter; glgX is transcribed independently. Surprisingly, the glgA mutant had decreased levels of high-molecular-weight exopolysaccharide after growth on glucose, but levels were normal after growth on galactose. A deletion mutant was constructed in order to generate a nonpolar mutation in glgA. This mutant had a phenotype similar to that of the Tn5 mutant, indicating that the enhanced respiration and symbiotic nitrogen fixation and decreased exopolysaccharide were due to mutation of glgA and not to a polar effect on a downstream gene. PMID- 11208784 TI - Effects exerted by transcriptional regulator PcaU from Acinetobacter sp. strain ADP1. AB - Protocatechuate degradation is accomplished in a multistep inducible catabolic pathway in Acinetobacter sp. strain ADP1. The induction is brought about by the transcriptional regulator PcaU in concert with the inducer protocatechuate. PcaU, a member of the new IclR family of transcriptional regulators, was shown to play a role in the activation of transcription at the promoter for the structural pca genes, leaving open the participation of additional activators. In this work we show that there is no PcaU-independent transcriptional activation at the pca gene promoter. The minimal inducer concentration leading to an induction response is 10(-5) M protocatechuate. The extent of expression of the pca genes was observed to depend on the nature of the inducing carbon source, and this is assumed to be caused by different internal levels of protocatechuate in the cells. The basal level of expression was shown to be comparatively high and to vary depending on the noninducing carbon source independent of PcaU. In addition to the activating function, in vivo results suggest a repressing function for PcaU at the pca gene promoter in the absence of an elevated inducer concentration. Expression at the pcaU gene promoter is independent of the growth condition but is subject to strong negative autoregulation. We propose a model in which PcaU exerts a repressor function both at its own promoter and at the structural gene promoter and in addition functions as an activator of transcription at the structural gene promoter at elevated inducer concentration. PMID- 11208785 TI - Ammonia switch-off of nitrogen fixation in the methanogenic archaeon Methanococcus maripaludis: mechanistic features and requirement for the novel GlnB homologues, NifI(1) and NifI(2). AB - Ammonia switch-off is the immediate inactivation of nitrogen fixation that occurs when a superior nitrogen source is encountered. In certain bacteria switch-off occurs by reversible covalent ADP-ribosylation of the dinitrogenase reductase protein, NifH. Ammonia switch-off occurs in diazotrophic species of the methanogenic Archaea as well. We showed previously that in Methanococcus maripaludis switch-off requires at least one of two novel homologues of glnB, a family of genes whose products play a central role in nitrogen sensing and regulation in bacteria. The novel glnB homologues have recently been named nifI(1) and nifI(2). Here we use in-frame deletions and genetic complementation analysis in M. maripaludis to show that the nifI(1) and nifI(2) genes are both required for switch-off. We could not detect ADP-ribosylation or any other covalent modification of dinitrogenase reductase during switch-off, suggesting that the mechanism differs from the well-studied bacterial system. Furthermore, switch-off did not affect nif gene transcription, nifH mRNA stability, or NifH protein stability. Nitrogenase activity resumed within a short time after ammonia was removed from a switched-off culture, suggesting that whatever the mechanism, it is reversible. We demonstrate the physiological importance of switch-off by showing that it allows growth to accelerate substantially when a diazotrophic culture is switched to ammonia. PMID- 11208786 TI - Characterization of a novel transferrin receptor in bovine strains of Pasteurella multocida. AB - Analysis of bovine respiratory isolates of Pasteurella multocida demonstrated that six of nine strains tested were capable of growth dependent upon bovine transferrin and of specifically binding ruminant transferrins. A single 82-kDa protein was affinity isolated from the P. multocida strains with immobilized bovine transferrin. In contrast to what has been observed in other species, binding of this protein to immobilized transferrin was specifically blocked by the N-lobe subfragment of bovine transferrin. A single gene encoding the 82-kDa protein was flanked by a leucyl-tRNA synthetase gene and an IS1060 element, in contrast to other species where genes encoding the two receptor proteins (TbpB and TbpA) are found in an operonic arrangement. A similar gene arrangement was observed in all of the receptor-positive strains, in spite of the observation that they belonged to different genomic groups. Analysis of the deduced amino acid sequence of the receptor protein indicated that it is a member of the TonB dependent outer membrane receptor family, and although it is related to transferrin and lactoferrin receptor proteins (TbpAs and LbpAs) from other species, it differs substantially from other members of this group. Amino acid alignments suggest that the reduced size (20 kDa smaller) of the P. multocida TbpA is primarily due to the absence of larger predicted external loops. Collectively these results suggest that P. multocida has a single, novel receptor protein (TbpA) that is capable of efficiently mediating iron acquisition from bovine transferrin without the involvement of a second receptor protein (TbpB). PMID- 11208788 TI - Transfer protein TraY of plasmid R1 stimulates TraI-catalyzed oriT cleavage in vivo. AB - The effect of TraY protein on TraI-catalyzed strand scission at the R1 transfer origin (oriT) in vivo was investigated. As expected, the cleavage reaction was not detected in Escherichia coli cells expressing tral and the integration host factor (IHF) in the absence of other transfer proteins. The TraM dependence of strand scission was found to be inversely correlated with the presence of TraY. Thus, the TraY and TraM proteins could each enhance cleaving activity at oriT in the absence of the other. In contrast, no detectable intracellular cleaving activity was exhibited by TraI in an IHF mutant strain despite the additional presence of both TraM and TraY. An essential role for IHF in this reaction in vivo is, therefore, implied. Mobilization experiments employing recombinant R1 oriT constructions and a heterologous conjugative helper plasmid were used to investigate the independent contributions of TraY and TraM to the R1 relaxosome during bacterial conjugation. In accordance with earlier observations, traY was dispensable for mobilization in the presence of traM, but mobilization did not occur in the absence of both traM and traY. Interestingly, although the cleavage assays demonstrate that TraM and TraY independently promote strand scission in vivo, TraM remained essential for mobilization of the R1 origin even in the presence of TraY. These findings suggest that, whereas TraY and TraM function may overlap to a certain extent in the R1 relaxosome, TraM additionally performs a second function that is essential for successful conjugative transmission of plasmid DNA. PMID- 11208787 TI - Natural genetic transformation of Streptococcus mutans growing in biofilms. AB - Streptococcus mutans is a bacterium that has evolved to be dependent upon a biofilm "lifestyle" for survival and persistence in its natural ecosystem, dental plaque. We initiated this study to identify the genes involved in the development of genetic competence in S. mutans and to assay the natural genetic transformability of biofilm-grown cells. Using genomic analyses, we identified a quorum-sensing peptide pheromone signaling system similar to those previously found in other streptococci. The genetic locus of this system comprises three genes, comC, comD, and comE, that encode a precursor to the peptide competence factor, a histidine kinase, and a response regulator, respectively. We deduced the sequence of comC and its active pheromone product and chemically synthesized the corresponding 21-amino-acid competence-stimulating peptide (CSP). Addition of CSP to noncompetent cells facilitated increased transformation frequencies, with typically 1% of the total cell population transformed. To further confirm the roles of these genes in genetic competence, we inactivated them by insertion duplication mutagenesis or allelic replacement followed by assays of transformation efficiency. We also demonstrated that biofilm-grown S. mutans cells were transformed at a rate 10- to 600-fold higher than planktonic S. mutans cells. Donor DNA included a suicide plasmid, S. mutans chromosomal DNA harboring a heterologous erythromycin resistance gene, and a replicative plasmid. The cells were optimally transformed during the formation of 8- to 16-h-old biofilms primarily consisting of microcolonies on solid surfaces. We also found that dead cells in the biofilms could act as donors of a chromosomally encoded antibiotic resistance determinant. This work demonstrated that a peptide pheromone system controls genetic competence in S. mutans and that the system functions optimally when the cells are living in actively growing biofilms. PMID- 11208789 TI - Diel expression of cell cycle-related genes in synchronized cultures of Prochlorococcus sp. strain PCC 9511. AB - The cell cycle of the chlorophyll b-possessing marine cyanobacterium Prochlorococcus is highly synchronized under natural conditions. To understand the underlying molecular mechanisms we cloned and sequenced dnaA and ftsZ, two key cell cycle-associated genes, and studied their expression. An axenic culture of Prochlorococcus sp. strain PCC 9511 was grown in a turbidostat with a 12 h-12 h light-dark cycle for 2 weeks. During the light periods, a dynamic light regimen was used in order to simulate the natural conditions found in the upper layers of the world's oceans. This treatment resulted in strong cell cycle synchronization that was monitored by flow cytometry. The steady-state mRNA levels of dnaA and ftsZ were monitored at 4-h intervals during four consecutive division cycles. Both genes exhibited clear diel expression patterns with mRNA maxima during the replication (S) phase. Western blot experiments indicated that the peak of FtsZ concentration occurred at night, i.e., at the time of cell division. Thus, the transcript accumulation of genes involved in replication and division is coordinated in Prochlorococcus sp. strain PCC 9511 and might be crucial for determining the timing of DNA replication and cell division. PMID- 11208790 TI - Lowering S-adenosylmethionine levels in Escherichia coli modulates C-to-T transition mutations. AB - Deoxycytosine methylase (Dcm) enzyme activity causes mutagenesis in vitro either directly by enzyme-induced deamination of cytosine to uracil in the absence of the methyl donor, S-adenosylmethionine (SAM), or indirectly through spontaneous deamination of [5-methyl]cytosine to thymine. Using a Lac reversion assay, we investigated the contribution of the first mechanism to Dcm mutagenesis in vivo by lowering the levels of SAM. Escherichia coli SAM levels were lowered by reducing SAM synthetase activity via the introduction of a metK84 allele or by hydrolyzing SAM using the bacteriophage T3 SAM hydrolase. The metK84 strains exhibited increased C-to-T mutagenesis. Expression of the T3 SAM hydrolase gene, under the control of the arabinose-inducible P(BAD) promoter, effectively reduced Dcm-mediated genomic DNA methylation. However, increased mutagenesis was not observed until extremely high arabinose concentrations were used, and genome methylation at Dcm sites was negligible. PMID- 11208791 TI - p-Hydroxyphenylacetic Acid Metabolism in Pseudomonas putida F6. AB - Pseudomonas putida F6 was found to metabolize p-hydroxyphenylacetic acid through 3,4-dihydroxyphenylacetic acid, 3,4-dihydroxymandelic acid, and 3,4 dihydroxybenzaldehyde. Cell extracts of P. putida F6 catalyze the NAD(P)H independent hydroxylation of p-hydroxyphenylacetic acid to 3,4 dihydroxyphenylacetic acid which is further oxidized to 3,4-dihydroxymandelic acid. Oxidation and decarboxylation of the latter yields 3,4 dihydroxybenzaldehyde. A red-brown color accompanies all of the above enzyme activities and is probably due to the polymerization of quinone-like compounds. 3,4-Dihydroxybenzaldehyde is further metabolized through extradiol ring cleavage. PMID- 11208792 TI - Analysis of lipooligosaccharide biosynthesis in the Neisseriaceae. AB - Neisserial lipooligosaccharide (LOS) contains three oligosaccharide chains, termed the alpha, beta, and gamma chains. We used Southern hybridization experiments on DNA isolated from various Neisseria spp. to determine if strains considered to be nonpathogenic possessed DNA sequences homologous with genes involved in the biosynthesis of these oligosaccharide chains. The presence or absence of specific genes was compared to the LOS profiles expressed by each strain, as characterized by their mobilities on sodium dodecyl sulfate polyacrylamide gel electrophoresis gel and their reactivities with various LOS specific monoclonal antibodies. A great deal of heterogeneity was seen with respect to the presence of genes encoding glycosyltransferases in Neisseria. All pathogenic species were found to possess DNA sequences homologous with the lgt gene cluster, a group of genes needed for the synthesis of the alpha chain. Some of these genes were also found to be present in strains considered to be nonpathogenic, such as Neisseria lactamica, N. subflava, and N. sicca. Some nonpathogenic Neisseria spp. were able to express high-molecular-mass LOS structures, even though they lacked the DNA sequences homologous with rfaF, a gene whose product must act before gonococcal and meningococcal LOS can be elongated. Using a PCR amplification strategy, in combination with DNA sequencing, we demonstrated that N. subflava 44 possessed lgtA, lgtB, and lgtE genes. The predicted amino acid sequence encoded by each of these genes suggested that they encoded functional proteins; however, structural analysis of LOS isolated from this strain indicated that the bulk of its LOS was not modified by these gene products. This suggests the existence of an additional regulatory mechanism that is responsible for the limited expression of these genes in this strain. PMID- 11208793 TI - Structural and immunochemical characterization of the lipooligosaccharides expressed by Neisseria subflava 44. AB - Neisserial lipooligosaccharides (LOSs) are a family of complex cell surface glycolipids. We used mass spectrometry techniques (electrospray ionization, collision-induced dissociation, and multiple step), combined with fluorophore assisted carbohydrate electrophoresis monosaccharide composition analysis, to determine the structure of the two low-molecular-mass LOS molecules (LOSI and LOSII) expressed by Neisseria subflava 44. We determined that LOSI contains one glucose on both the alpha and beta chains. LOSII is structurally related to LOSI and differs from it by the addition of a hexose (either glucose or galactose) on the alpha chain. LOSI and LOSII were able to bind monoclonal antibody (MAb) 25-1 LC1 when analyzed by Western blotting experiments. We used a set of genetically defined Neisseria gonorrhoeae mutants that expressed single defined LOS epitopes and a group of Neisseria meningitidis strains that expresses chemically defined LOS components to determine the structures recognized by MAb 25-1-LC1. We found that extensions onto the beta-chain glucose of LOSI block the recognition by this MAb, as does further elongation from the LOSII alpha chain. The LOSI structure was determined to be the minimum structure that is recognized by MAb 25-1-LC1. PMID- 11208794 TI - Periplasmic transit and disulfide bond formation of the autotransported Shigella protein IcsA. AB - The Shigella outer membrane protein IcsA belongs to the family of type V secreted (autotransported) virulence factors. Members of this family mediate their own translocation across the bacterial outer membrane: the carboxy-terminal beta domain forms a beta barrel channel in the outer membrane through which the amino terminal alpha domain passes. IcsA, which is localized at one pole of the bacterium, mediates actin assembly by Shigella, which is essential for bacterial intracellular movement and intercellular dissemination. Here, we characterize the transit of IcsA across the periplasm during its secretion. We show that an insertion in the dsbB gene, whose gene product mediates disulfide bond formation of many periplasmic intermediates, does not affect the surface expression or unipolar targeting of IcsA. However, IcsA forms one disulfide bond in the periplasm in a DsbA/DsbB-dependent fashion. Furthermore, cellular fractionation studies reveal that IcsA has a transient soluble periplasmic intermediate. Our data also suggest that IcsA is folded in a proteinase K-resistant state in the periplasm. From these data, we propose a novel model for the secretion of IcsA that may be applicable to other autotransported proteins. PMID- 11208795 TI - Exchange of Xcp (Gsp) secretion machineries between Pseudomonas aeruginosa and Pseudomonas alcaligenes: species specificity unrelated to substrate recognition. AB - Pseudomonas aeruginosa and Pseudomonas alcaligenes are gram-negative bacteria that secrete proteins using the type II or general secretory pathway, which requires at least 12 xcp gene products (XcpA and XcpP to -Z). Despite strong conservation of this secretion pathway, gram-negative bacteria usually cannot secrete exoproteins from other species. Based on results obtained with Erwinia, it has been proposed that the XcpP and/or XcpQ homologs determine this secretion specificity (M. Linderberg, G. P. Salmond, and A. Collmer, Mol. Microbiol. 20:175 190, 1996). In the present study, we report that XcpP and XcpQ of P. alcaligenes could not substitute for their respective P. aeruginosa counterparts. However, these complementation failures could not be correlated to species-specific recognition of exoproteins, since these bacteria could secrete exoproteins of each other. Moreover, when P. alcaligenes xcpP and xcpQ were expressed simultaneously in a P. aeruginosa xcpPQ deletion mutant, complementation was observed, albeit only on agar plates and not in liquid cultures. After growth in liquid culture the heat-stable P. alcaligenes XcpQ multimers were not detected, whereas monomers were clearly visible. Together, our results indicate that the assembly of a functional Xcp machinery requires species-specific interactions between XcpP and XcpQ and between XcpP or XcpQ and another, as yet uncharacterized component(s). PMID- 11208796 TI - Anaerobic metabolism of 3-hydroxybenzoate by the denitrifying bacterium Thauera aromatica. AB - The anaerobic metabolism of 3-hydroxybenzoate was studied in the denitrifying bacterium Thauera aromatica. Cells grown with this substrate were adapted to grow with benzoate but not with 4-hydroxybenzoate. Vice versa, 4-hydroxybenzoate-grown cells did not utilize 3-hydroxybenzoate. The first step in 3-hydroxybenzoate metabolism is a coenzyme A (CoA) thioester formation, which is catalyzed by an inducible 3-hydroxybenzoate-CoA ligase. The enzyme was purified and characterized. Further metabolism of 3-hydroxybenzoyl-CoA by cell extract required MgATP and was coupled to the oxidation of 2 mol of reduced viologen dyes per mol of substrate added. Purification of the 3-hydroxybenzoyl-CoA reducing enzyme revealed that this activity was due to benzoyl-CoA reductase, which reduced the 3-hydroxy analogue almost as efficiently as benzoyl-CoA. The further metabolism of the alicyclic dienoyl-CoA product containing the hydroxyl substitution obviously required additional specific enzymes. Comparison of the protein pattern of 3-hydroxybenzoate-grown cells with benzoate-grown cells revealed several 3-hydroxybenzoate-induced proteins; the N-terminal amino acid sequences of four induced proteins were determined and the corresponding genes were identified and sequenced. A cluster of six adjacent genes contained the genes for substrate-induced proteins 1 to 3; this cluster may not yet be complete. Protein 1 is a short-chain alcohol dehydrogenase. Protein 2 is a member of enoyl-CoA hydratase enzymes. Protein 3 was identified as 3-hydroxybenzoate-CoA ligase. Protein 4 is another member of the enoyl-CoA hydratases. In addition, three genes coding for enzymes of beta-oxidation were present. The anaerobic 3 hydroxybenzoate metabolism here obviously combines an enzyme (benzoyl-CoA reductase) and electron carrier (ferredoxin) of the general benzoyl-CoA pathway with enzymes specific for the 3-hydroxybenzoate pathway. This raises some questions concerning the regulation of both pathways. PMID- 11208797 TI - Effect of sequences of the active-site dipeptides of DsbA and DsbC on in vivo folding of multidisulfide proteins in Escherichia coli. AB - We have examined the role of the active-site CXXC central dipeptides of DsbA and DsbC in disulfide bond formation and isomerization in the Escherichia coli periplasm. DsbA active-site mutants with a wide range of redox potentials were expressed either from the trc promoter on a multicopy plasmid or from the endogenous dsbA promoter by integration of the respective alleles into the bacterial chromosome. The dsbA alleles gave significant differences in the yield of active murine urokinase, a protein containing 12 disulfides, including some that significantly enhanced urokinase expression over that allowed by wild-type DsbA. No direct correlation between the in vitro redox potential of dsbA variants and the urokinase yield was observed. These results suggest that the active-site CXXC motif of DsbA can play an important role in determining the folding of multidisulfide proteins, in a way that is independent from DsbA's redox potential. However, under aerobic conditions, there was no significant difference among the DsbA mutants with respect to phenotypes depending on the oxidation of proteins with few disulfide bonds. The effect of active-site mutations in the CXXC motif of DsbC on disulfide isomerization in vivo was also examined. A library of DsbC expression plasmids with the active-site dipeptide randomized was screened for mutants that have increased disulfide isomerization activity. A number of DsbC mutants that showed enhanced expression of a variant of human tissue plasminogen activator as well as mouse urokinase were obtained. These DsbC mutants overwhelmingly contained an aromatic residue at the C-terminal position of the dipeptide, whereas the N-terminal residue was more diverse. Collectively, these data indicate that the active sites of the soluble thiol- disulfide oxidoreductases can be modulated to enhance disulfide isomerization and protein folding in the bacterial periplasmic space. PMID- 11208798 TI - Subunit interactions and glutamine utilization by Escherichia coli imidazole glycerol phosphate synthase. AB - A selection strategy has been developed to identify amino acid residues involved in subunit interactions that coordinate the two half-reactions catalyzed by glutamine amidotransferases. The protein structures known for this class of enzymes have revealed that ammonia is shuttled over long distances and that each amidotransferase evolved different molecular tunnels for this purpose. The heterodimeric Escherichia coli imidazole glycerol phosphate (IGP) synthase was probed to assess if residues in the substrate amination subunit (HisF) are critical for the glutaminase activity in the HisH subunit. The activity of the HisH subunit is dependent upon binding of the nucleotide substrate at the HisF active site. This regulatory function has been exploited as a biochemical selection of mutant HisF subunits that retain full activity with ammonia as a substrate but, when constituted as a holoenzyme with wild-type HisH, impair the glutamine-dependent activity of IGP synthase. The steady-state kinetic constants for these IGP synthases with HisF alleles showed three distinct effects depending upon the site of mutation. For example, mutation of the R5 residue has similar effects on the glutamine-dependent amidotransfer reaction; however, k(cat)/K(m) for the glutaminase half-reaction was increased 10-fold over that for the wild type enzyme with nucleotide substrate. This site appears essential for coupling of the glutamine hydrolysis and ammonia transfer steps and is the first example of a site remote to the catalytic triad that modulates the process. The results are discussed in the context of recent X-ray crystal structures of glutamine amidotransferases that relate the glutamine binding and acceptor binding sites. PMID- 11208800 TI - Size comparisons among integral membrane transport protein homologues in bacteria, Archaea, and Eucarya. AB - Integral membrane proteins from over 20 ubiquitous families of channels, secondary carriers, and primary active transporters were analyzed for average size differences between homologues from the three domains of life: Bacteria, Archaea, and Eucarya. The results showed that while eucaryotic homologues are consistently larger than their bacterial counterparts, archaeal homologues are significantly smaller. These size differences proved to be due primarily to variations in the sizes of hydrophilic domains localized to the N termini, the C termini, or specific loops between transmembrane alpha-helical spanners, depending on the family. Within the Eucarya domain, plant homologues proved to be substantially smaller than their animal and fungal counterparts. By contrast, extracytoplasmic receptors of ABC-type uptake systems in Archaea proved to be larger on average than those of their bacterial homologues, while cytoplasmic enzymes from different organisms exhibited little or no significant size differences. These observations presumably reflect evolutionary pressure and molecular mechanisms that must have been operative since these groups of organisms diverged from each other. PMID- 11208799 TI - Chlorocatechols substituted at positions 4 and 5 are substrates of the broad spectrum chlorocatechol 1,2-dioxygenase of Pseudomonas chlororaphis RW71. AB - The nucleotide sequence of a 10,528-bp region comprising the chlorocatechol pathway gene cluster tetRtetCDEF of the 1,2,3,4-tetrachlorobenzene via the tetrachlorocatechol-mineralizing bacterium Pseudomonas chlororaphis RW71 (T. Potrawfke, K. N. Timmis, and R.-M. Wittich, Appl. Environ. Microbiol. 64:3798 3806, 1998) was analyzed. The chlorocatechol 1,2-dioxygenase gene tetC was cloned and overexpressed in Escherichia coli. The recombinant gene product was purified, and the alpha,alpha-homodimeric TetC was characterized. Electron paramagnetic resonance measurements confirmed the presence of a high-spin-state Fe(III) atom per monomer in the holoprotein. The productive transformation by purified TetC of chlorocatechols bearing chlorine atoms in positions 4 and 5 provided strong evidence for a significantly broadened substrate spectrum of this dioxygenase compared with other chlorocatechol dioxygenases. The conversion of 4,5-dichloro- or tetrachlorocatechol, in the presence of catechol, displayed strong competitive inhibition of catechol turnover. 3-Chlorocatechol, however, was simultaneously transformed, with a rate similar to that of the 4,5-halogenated catechols, indicating similar specificity constants. These novel characteristics of TetC thus differ significantly from results obtained from hitherto analyzed catechol 1,2-dioxygenases and chlorocatechol 1,2-dioxygenases. PMID- 11208801 TI - Cooperativity between KorB and TrbA repressors of broad-host-range plasmid RK2. AB - The KorB and TrbA proteins of broad-host-range plasmid RK2 are key regulators of the plasmid genes required for conjugative transfer. trbBp is the primary promoter responsible for expression of mating pair formation genes. We show that despite the targets for KorB and TrbA at trbBp being about 165 bp apart, 189 bp upstream of the transcription start point and overlapping the -10 region, respectively, these two proteins show up to 10-fold cooperativity for the repression of trbBp. Deletion analysis of TrbA showed that the C-terminal domain (CTD), which has a high degree of sequence conservation with the CTD of KorA, is required for this cooperativity with KorB. Western blotting demonstrated that the apparently mutual enhancement of repression is not due simply to elevation of repressor level by the presence of the second protein, suggesting that the basis for cooperativity is interaction between KorB and TrbA bound at their respective operators. PMID- 11208802 TI - Evidence of multiple regulatory functions for the PtsN (IIA(Ntr)) protein of Pseudomonas putida. AB - The ptsN gene of Pseudomonas putida encodes IIA(Ntr), a protein of the phosphoenol pyruvate:sugar phosphotransferase (PTS) system which is required for the C source inhibition of the sigma(54)-dependent promoter Pu of the TOL (toluate degradation) plasmid pWW0. Using two-dimensional gel electrophoresis, we have examined the effect of ptsN disruption on the general expression pattern of P. putida. To this end, cells were grown in the presence or absence of glucose, and a 1,117-spot subset of the P. putida proteome was used as a reference for comparisons. Among all gene products whose expression was lowered by this carbon source (247 spots [about 22%]), only 6 behaved as Pu (i.e., were depressed in the ptsN background). This evidenced only a minor role for IIA(Ntr) in the extensive inhibition of gene expression in P. putida caused by glucose. However, the same experiments revealed a large incidence of glucose-independent effects brought about by the ptsN mutation. As many as 108 spots (ca. 9% of the cell products analyzed) were influenced, positively or negatively, by the loss of IIA(Ntr). By matching this pattern with that of an rpoN::OmegaKm strain of P. putida, which lacks the sigma(54) protein, we judge that most proteins whose expression was affected by ptsN were unrelated to the alternative sigma factor. These data suggest a role of IIA(Ntr) as a general regulator, independent of the presence of repressive carbon sources and not limited to sigma(54)-dependent genes. PMID- 11208803 TI - Connection between poly-beta-hydroxybutyrate biosynthesis and growth on C(1) and C(2) compounds in the methylotroph Methylobacterium extorquens AM1. AB - Several DNA regions containing genes involved in poly-beta-hydroxybutyrate (PHB) biosynthesis and degradation and also in fatty acid degradation were identified from genomic sequence data and have been characterized in the serine cycle facultative methylotroph Methylobacterium extorquens AM1. Genes involved in PHB biosynthesis include those encoding beta-ketothiolase (phaA), NADPH-linked acetoacetyl coenzyme A (acetyl-CoA) reductase (phaB), and PHB synthase (phaC). phaA and phaB are closely linked on the chromosome together with a third gene with identity to a regulator of PHB granule-associated protein, referred to as orf3. phaC was unlinked to phaA and phaB. Genes involved in PHB degradation include two unlinked genes predicted to encode intracellular PHB depolymerases (depA and depB). These genes show a high level of identity with each other at both DNA and amino acid levels. In addition, a gene encoding beta-hydroxybutyrate dehydrogenase (hbd) was identified. Insertion mutations were introduced into depA, depB, phaA, phaB, phaC, and hbd and also in a gene predicted to encode crotonase (croA), which is involved in fatty acid degradation, to investigate their role in PHB cycling. Mutants in depA, depB, hbd, and croA all produced normal levels of PHB, and the only growth phenotype observed was the inability of the hbd mutant to grow on beta-hydroxybutyrate. However, the phaA, phaB, and phaC mutants all showed defects in PHB synthesis. Surprisingly, these mutants also showed defects in growth on C(1) and C(2) compounds and, for phaB, these defects were rescued by glyoxylate supplementation. These results suggest that beta hydroxybutyryl-CoA is an intermediate in the unknown pathway that converts acetyl CoA to glyoxylate in methylotrophs and Streptomyces spp. PMID- 11208804 TI - Role of alginate and its O acetylation in formation of Pseudomonas aeruginosa microcolonies and biofilms. AB - Attenuated total reflection/Fourier transform-infrared spectrometry (ATR/FT-IR) and scanning confocal laser microscopy (SCLM) were used to study the role of alginate and alginate structure in the attachment and growth of Pseudomonas aeruginosa on surfaces. Developing biofilms of the mucoid (alginate-producing) cystic fibrosis pulmonary isolate FRD1, as well as mucoid and nonmucoid mutant strains, were monitored by ATR/FT-IR for 44 and 88 h as IR absorbance bands in the region of 2,000 to 1,000 cm(-1). All strains produced biofilms that absorbed IR radiation near 1,650 cm(-1) (amide I), 1,550 cm(-1) (amide II), 1,240 cm(-1) (P==O stretching, C---O---C stretching, and/or amide III vibrations), 1,100 to 1,000 cm(-1) (C---OH and P---O stretching) 1,450 cm(-1), and 1,400 cm(-1). The FRD1 biofilms produced spectra with an increase in relative absorbance at 1,060 cm(-1) (C---OH stretching of alginate) and 1,250 cm(-1) (C---O stretching of the O-acetyl group in alginate), as compared to biofilms of nonmucoid mutant strains. Dehydration of an 88-h FRD1 biofilm revealed other IR bands that were also found in the spectrum of purified FRD1 alginate. These results provide evidence that alginate was present within the FRD1 biofilms and at greater relative concentrations at depths exceeding 1 micrometer, the analysis range for the ATR/FT-IR technique. After 88 h, biofilms of the nonmucoid strains produced amide II absorbances that were six to eight times as intense as those of the mucoid FRD1 parent strain. However, the cell densities in biofilms were similar, suggesting that FRD1 formed biofilms with most cells at depths that exceeded the analysis range of the ATR/FT-IR technique. SCLM analysis confirmed this result, demonstrating that nonmucoid strains formed densely packed biofilms that were generally less than 6 micrometer in depth. In contrast, FRD1 produced microcolonies that were approximately 40 micrometer in depth. An algJ mutant strain that produced alginate lacking O-acetyl groups gave an amide II signal approximately fivefold weaker than that of FRD1 and produced small microcolonies. After 44 h, the algJ mutant switched to the nonmucoid phenotype and formed uniform biofilms, similar to biofilms produced by the nonmucoid strains. These results demonstrate that alginate, although not required for P. aeruginosa biofilm development, plays a role in the biofilm structure and may act as intercellular material, required for formation of thicker three-dimensional biofilms. The results also demonstrate the importance of alginate O acetylation in P. aeruginosa biofilm architecture. PMID- 11208806 TI - Starchless mutants of Chlamydomonas reinhardtii lack the small subunit of a heterotetrameric ADP-glucose pyrophosphorylase. AB - ADP-glucose synthesis through ADP-glucose pyrophosphorylase defines the major rate-controlling step of storage polysaccharide synthesis in both bacteria and plants. We have isolated mutant strains defective in the STA6 locus of the monocellular green alga Chlamydomonas reinhardtii that fail to accumulate starch and lack ADP-glucose pyrophosphorylase activity. We show that this locus encodes a 514-amino-acid polypeptide corresponding to a mature 50-kDa protein with homology to vascular plant ADP-glucose pyrophosphorylase small-subunit sequences. This gene segregates independently from the previously characterized STA1 locus that encodes the large 53-kDa subunit of the same heterotetramer enzyme. Because STA1 locus mutants have retained an AGPase but exhibit lower sensitivity to 3 phosphoglyceric acid activation, we suggest that the small and large subunits of the enzyme define, respectively, the catalytic and regulatory subunits of AGPase in unicellular green algae. We provide preliminary evidence that both the small subunit mRNA abundance and enzyme activity, and therefore also starch metabolism, may be controlled by the circadian clock. PMID- 11208805 TI - Identification and characterization of the dif Site from Bacillus subtilis. AB - Bacteria with circular chromosomes have evolved systems that ensure multimeric chromosomes, formed by homologous recombination between sister chromosomes during DNA replication, are resolved to monomers prior to cell division. The chromosome dimer resolution process in Escherichia coli is mediated by two tyrosine family site-specific recombinases, XerC and XerD, and requires septal localization of the division protein FtsK. The Xer recombinases act near the terminus of chromosome replication at a site known as dif (Ecdif). In Bacillus subtilis the RipX and CodV site-specific recombinases have been implicated in an analogous reaction. We present here genetic and biochemical evidence that a 28-bp sequence of DNA (Bsdif), lying 6 degrees counterclockwise from the B. subtilis terminus of replication (172 degrees ), is the site at which RipX and CodV catalyze site specific recombination reactions required for normal chromosome partitioning. Bsdif in vivo recombination did not require the B. subtilis FtsK homologues, SpoIIIE and YtpT. We also show that the presence or absence of the B. subtilis SPbeta-bacteriophage, and in particular its yopP gene product, appears to strongly modulate the extent of the partitioning defects seen in codV strains and, to a lesser extent, those seen in ripX and dif strains. PMID- 11208807 TI - Cytoplasmic filament-deficient mutant of Treponema denticola has pleiotropic defects. AB - In Treponema denticola, a ribbon-like structure of cytoplasmic filaments spans the cytoplasm at all stages of the cell division process. Insertional inactivation was used as a first step to determine the function of the cytoplasmic filaments. A suicide plasmid was constructed that contained part of cfpA and a nonpolar erythromycin resistance cassette (ermF and ermAM) inserted near the beginning of the gene. The plasmid was electroporated into T. denticola, and double-crossover recombinants which had the chromosomal copy of cfpA insertionally inactivated were selected. Immunoblotting and electron microscopy confirmed the lack of cytoplasmic filaments. The mutant was further analyzed by dark-field microscopy to determine cell morphology and by the binding of two fluorescent dyes to DNA to assess the distribution of cellular nucleic acids. The cytoplasmic filament protein-deficient mutant exhibited pleiotropic defects, including highly condensed chromosomal DNA, compared to the homogeneous distribution of the DNA throughout the cytoplasm in a wild-type cell. Moreover, chains of cells are formed by the cytoplasmic filament-deficient mutant, and those cells show reduced spreading in agarose, which may be due to the abnormal cell length. The chains of cells and the highly condensed chromosomal DNA suggest that the cytoplasmic filaments may be involved in chromosome structure, segregation, or the cell division process in Treponema. PMID- 11208808 TI - umuDC-dnaQ Interaction and its implications for cell cycle regulation and SOS mutagenesis in Escherichia coli. AB - The Escherichia coli SOS-regulated umuDC gene products participate in a DNA damage checkpoint control and in translesion DNA synthesis. Specific interactions involving the UmuD and UmuD' proteins, both encoded by the umuD gene, and components of the replicative DNA polymerase, Pol III, appear to be important for regulating these two biological activities of the umuDC gene products. Here we show that overproduction of the epsilon proofreading subunit of Pol III suppresses the cold sensitivity normally associated with overexpression of the umuDC gene products. Our results suggest that this suppression is attributable to specific interactions between UmuD or UmuD' and the C-terminal domain of epsilon. PMID- 11208809 TI - Nitrogen-regulated group 2 sigma factor from Synechocystis sp. strain PCC 6803 involved in survival under nitrogen stress. AB - The expression of sll1689, an open reading frame from the cyanobacterium Synechocystis sp. strain PCC 6803 putatively encoding a member of the sigma(70) family of sigma factors, appears to be regulated by the nitrogen control transcription factor NtcA. Disruption of sll1689 had no noticeable effect on exponential growth, identifying its product as a member of the group 2, nonessential class of sigma(70)-like sigma factors; however, this disruption decreased the viability of the cells after long periods of nitrogen starvation. We have named this gene rpoD2-V. The expression of glnN, encoding a type III glutamine synthetase, was impaired in strains bearing an inactivated copy of the rpoD2-V gene. PMID- 11208810 TI - Transcript analysis of multiple copies of amo (encoding ammonia monooxygenase) and hao (encoding hydroxylamine oxidoreductase) in Nitrosomonas europaea. AB - The genes encoding ammonia monooxygenase (amoCAB), hydroxylamine oxidoreductase (hao), and the c-type cytochrome c-554 (hcy) are present in multiple copies in the genome of Nitrosomonas europaea. The upstream regions of the two copies of amoC, the three copies of hao, and one copy of hcy were cloned and sequenced. Primer extension reactions were done to identify transcription start sites for these genes, as well as for amoA. Putative sigma(70) promoter sequences were found associated with all but one of the mapped transcription start sites. Primer extensions were done with amoC primers using RNA harvested from cells incubated with and without ammonium. The experiments suggested that N. europaea cells may be able to use different promoters in the presence and absence of ammonium. PMID- 11208811 TI - Experimental evolution of enzyme temperature activity profile: selection in vivo and characterization of low-temperature-adapted mutants of Pyrococcus furiosus ornithine carbamoyltransferase. AB - We have obtained mutants of Pyrococcus furiosus ornithine carbamoyltransferase active at low temperatures by selecting for complementation of an appropriate yeast mutant after in vivo mutagenesis. The mutants were double ones, still complementing at 15 degrees C, a temperature already in the psychrophilic range. Their kinetic analysis is reported. PMID- 11208812 TI - Preferential cleavage of degradative intermediates of rpsT mRNA by the Escherichia coli RNA degradosome. AB - RNase E, the principal RNase capable of initiating mRNA decay, preferentially attacks 5'-monophosphorylated over 5'-triphosphorylated substrates. Site-specific cleavage in vitro of the rpsT mRNA by RNase H directed by chimeric 2'-O-methyl oligonucleotides was employed to create truncated RNAs which are identical to authentic degradative intermediates. The rates of cleavage of two such intermediates by RNase E in the RNA degradosome are significantly faster (2.5- to 8-fold) than that of intact RNA. This verifies the preference of RNase E for degradative intermediates and can explain the frequent "all-or-none" behavior of mRNAs during the decay process. PMID- 11208813 TI - Na(+)/glutamine (asparagine) cotransport by Staphylococcus lugdunensis and Corynebacterium amycolatum. AB - Staphylococcus lugdunensis and Corynebacterium amycolatum each have a Na(+)/glutamine cotransporter that displays an ordered reaction sequence at the extracellular surface, with sodium binding (K(m) of 6.5 mM) before glutamine (K(m) of 50 microM). Asparagine is low-affinity substrate (K(m) approximately 1 mM) for each system. PMID- 11208816 TI - Preoperative chemoradiotherapy for esophageal cancer. PMID- 11208814 TI - Drosophila melanogaster casein kinase II interacts with and phosphorylates the basic helix-loop-helix proteins m5, m7, and m8 derived from the Enhancer of split complex. AB - Drosophila melanogaster casein kinase II (DmCKII) is composed of catalytic (alpha) and regulatory (beta) subunits associated as an alpha2beta2 heterotetramer. Using the two-hybrid system, we have screened a D. melanogaster embryo cDNA library for proteins that interact with DmCKIIalpha. One of the cDNAs isolated in this screen encodes m7, a basic helix-loop-helix (bHLH)-type transcription factor encoded by the Enhancer of split complex (E(spl)C), which regulates neurogenesis. m7 interacts with DmCKIIalpha but not with DmCKIIbeta, suggesting that this interaction is specific for the catalytic subunit of DmCKII. In addition to m7, we demonstrate that DmCKIIalpha also interacts with two other E(spl)C-derived bHLH proteins, m5 and m8, but not with other members, such as m3 and mC. Consistent with the specificity observed for the interaction of DmCKIIalpha with these bHLH proteins, sequence alignment suggests that only m5, m7, and m8 contain a consensus site for phosphorylation by CKII within a subdomain unique to these three proteins. Accordingly, these three proteins are phosphorylated by DmCKIIalpha, as well as by the alpha2beta2 holoenzyme purified from Drosophila embryos. In line with the prediction of a single consensus site for CKII, replacement of Ser(159) of m8 with either Ala or Asp abolishes phosphorylation, identifying this residue as the site of phosphorylation. We also demonstrate that m8 forms a direct physical complex with purified DmCKII, corroborating the observed two-hybrid interaction between these proteins. Finally, substitution of Ser(159) of m8 with Ala attenuates interaction with DmCKIIalpha, whereas substitution with Asp abolishes the interaction. These studies constitute the first demonstration that DmCKII interacts with and phosphorylates m5, m7, and m8 and suggest a biochemical and/or structural basis for the functional equivalency of these bHLH proteins that is observed in the context of neurogenesis. PMID- 11208817 TI - Markers, markers everywhere..... Prognosis in colorectal cancer--time for a new approach. PMID- 11208818 TI - Phase II trial of intratumoral administration of ONYX-015, a replication selective adenovirus, in patients with refractory head and neck cancer. AB - PURPOSE: To determine the safety, humoral immune response replication, and activity of multiple intratumoral injections of ONYX-015 (replication selective adenovirus) in patients with recurrent squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: This phase II trial enrolled patients with SCCHN who had recurrence/relapse after prior conventional treatment. Patients received ONYX-015 at a dose of 2 x 10(11) particles via intratumoral injection for either 5 consecutive days (standard) or twice daily for 2 consecutive weeks (hyperfractionated) during a 21-day cycle. Patients were monitored for tumor response, toxicity, and antibody formation. RESULTS: Forty patients (30 standard and 10 hyperfractionated) received 533 injections of ONYX-015. Standard treatment resulted in 14% partial to complete regression, 41% stable disease, and 45% progressive disease rates. Hyperfractionated treatment resulted in 10% complete response, 62% stable disease, and 29% progressive disease rates. Treatment related toxicity included mild to moderate fever (67% overall) and injection site pain (47% on the standard regimen, 80% on the hyperfractionated regimen). Detectable circulating ONYX-015 genome suggestive of intratumoral replication was identified in 41% of tested patients on days 5 and 6 of cycle 1; 9% of patients had evidence of viral replication 10 days after injection during cycle 1, and no patients had evidence of replication > or = 22 days after injection. CONCLUSION: ONYX-015 can be safely administered via intratumoral injection to patients with recurrent/refractory SCCHN. ONYX-015 viremia is transient. Evidence of modest antitumoral activity is suggested. PMID- 11208819 TI - K-ras and p16 aberrations confer poor prognosis in human colorectal cancer. AB - PURPOSE: Mutations in the K-ras gene are frequent in human cancer. ras activation in primary cells results in a cellular senescence phenotype that is precluded by inactivation of p16. At the clinical level, this may imply a differential behavior for tumors with alternative or cooperative activation of K-ras function and impairment of p16 pathways. PATIENTS AND METHODS: We have determined the presence of mutations in the K-ras gene and the methylation status of p16 promoter in a series of 119 prospectively collected colorectal carcinomas. p53 mutations and p14 alternative reading frame methylation status were also assessed. Associations with survival were investigated. RESULTS: K-ras mutations were present in 44 (38%) of 115 cases, and p16 methylation was present in 42 (37%) of 113 cases. p53 mutations were detected in 50% (56 of 115) and p14 methylation in 29% (32 of 112) of cases. K-ras and p16 alterations were independent genetic events. Presence of K-ras or p16 genetic alterations (analyzed independently) was associated with shorter survival, although differences were not statistically significant. Cox analysis of the two variables combined showed a diminished survival as the results of an interaction between p16 and K-ras. Alternative alteration of K-ras and p16 genes was an independent prognostic factor in human colorectal cancer in univariate and multivariate analysis. Differences were maintained when cases undergoing radical surgery and without distant metastases were considered. CONCLUSION: These results suggest that the combined K-ras and p16 analyses may be of prognostic use in human colorectal cancer. PMID- 11208820 TI - Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. AB - PURPOSE: A pilot study of 43 patients with potentially resectable esophageal carcinoma treated with an intensive regimen of preoperative chemoradiation with cisplatin, fluorouracil, and vinblastine before surgery showed a median survival of 29 months in comparison with the 12-month median survival of 100 historical controls treated with surgery alone at the same institution. We designed a randomized trial to compare survival for patients treated with this preoperative chemoradiation regimen versus surgery alone. MATERIALS AND METHODS: One hundred patients with esophageal carcinoma were randomized to receive either surgery alone (arm I) or preoperative chemoradiation (arm II) with cisplatin 20 mg/m2/d on days 1 through 5 and 17 through 21, fluorouracil 300 mg/m2/d on days 1 through 21, and vinblastine 1 mg/m2/d on days 1 through 4 and 17 through 20. Radiotherapy consisted of 1.5-Gy fractions twice daily, Monday through Friday over 21 days, to a total dose of 45 Gy. Transhiatal esophagectomy with a cervical esophagogastric anastomosis was performed on approximately day 42. RESULTS: At median follow-up of 8.2 years, there is no significant difference in survival between the treatment arms. Median survival is 17.6 months in arm I and 16.9 months in arm II. Survival at 3 years was 16% in arm I and 30% in arm II (P = .15). This study was statistically powered to detect a relatively large increase in median survival from 1 year to 2.2 years, with at least 80% power. CONCLUSION: This randomized trial of preoperative chemoradiation versus surgery alone for patients with potentially resectable esophageal carcinoma did not demonstrate a statistically significant survival difference. PMID- 11208821 TI - Phase II study of docetaxel, doxorubicin, and cyclophosphamide as first-line chemotherapy for metastatic breast cancer. AB - PURPOSE: This pilot phase II study investigated the efficacy and toxicity of docetaxel with doxorubicin and cyclophosphamide (TAC) as first-line chemotherapy for anthracycline-naive patients with metastatic breast cancer. PATIENTS AND METHODS: Fifty-four patients received a total of 359 courses consisting of docetaxel 75 mg/m2 given intravenously (IV) over 1 hour, preceded by IV doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 for a maximum of eight 3-week cycles. RESULTS: After an independent panel review, the overall objective response rate was 77% (complete response, 6%). Overall objective response rates in patients with visceral, bone, and liver involvement were 82%, 82%, and 80%, respectively. Median duration of response was 52 weeks, and median time to progression was 42 weeks. With a median follow-up of 32 months, the median survival had not yet been reached, whereas the 2-year survival was 57%. The main toxicities were hematologic (neutropenia grade 3/4 in 100% of patients and 95% of cycles; febrile neutropenia in 34% of patients and 9% of cycles). Documented grade 3 infection was seen in one patient (2%) in one cycle, and no toxic death was reported. Severe acute or chronic nonhematologic adverse events were infrequent, and docetaxel-specific toxicities (such as fluid retention and nail changes) were mild, with only one patient being discontinued for fluid retention. Congestive heart failure was seen in two patients (4%). CONCLUSION: TAC is an active and manageable regimen that has been chosen as the basis of five randomized phase III trials, including two pivotal studies comparing TAC to fluorouracil plus doxorubicin and cyclophosphamide in the metastatic and adjuvant treatment of breast cancer. PMID- 11208822 TI - Adjuvant tamoxifen: predictors of use, side effects, and discontinuation in older women. AB - PURPOSE: To identify predictors of adjuvant tamoxifen use, side effects, and discontinuation in older women. PATIENTS AND METHODS: We followed a cohort of 303 women > or = 55 years of age diagnosed with stage I or stage II breast cancer for nearly 3 years. Data were collected from women's surgical records and from computer-assisted telephone interviews at 5, 21, and 33 months after primary tumor therapy. RESULTS: Two hundred ninety-two (96%) of 303 patients in the study provided information about tamoxifen use. Tamoxifen use was reported by 189 patients (65%); 26 (15%) discontinued use during the follow-up period. Patients who were 65 to 74 years of age (relative to those 55 to 64 years of age), had stage II disease, were estrogen receptor-positive, saw a greater number of breast cancer physicians, and had better perceptions of their abilities to discuss treatment options with physicians had greater odds of tamoxifen use. Those who had better physical function, had received standard primary tumor therapy, and had obtained helpful breast cancer information from books or magazines had lesser odds of tamoxifen use. Patients > or = 75 years of age (relative to those 55 to 64 years of age) and patients with better emotional health had significantly lesser odds of reporting side effects. Patients who were estrogen receptor positive were less likely to stop taking tamoxifen; patients who experienced side effects were more likely to stop taking tamoxifen. CONCLUSION: Deviations from a prescribed course of adjuvant tamoxifen occur relatively frequently. The clinical consequences of this deviation need to be identified. PMID- 11208823 TI - Response to cyclophosphamide, methotrexate, and fluorouracil in lymph node positive breast cancer according to HER2 overexpression and other tumor biologic variables. AB - PURPOSE: There is considerable interest in biologic markers able to predict the response of cancer patients to therapy. HER2 overexpression is a potential indicator of responsiveness to doxorubicin and paclitaxel and of unresponsiveness to tamoxifen in breast carcinoma patients. However, the significance of HER2 overexpression in responsiveness to cyclophosphamide, methotrexate, and fluorouracil (CMF) has remained unclear. In this study, we investigated this issue in the 386 breast cancer patients in the first CMF controlled clinical trial with a 20-year follow-up. PATIENTS AND METHODS: Node-positive breast carcinoma patients were randomly assigned to receive either no further treatment after radical mastectomy (179 women) or 12 monthly cycles of adjuvant CMF chemotherapy (207 women). Overexpression of HER2 and the status of other tumor variables was assessed by immunohistochemistry in at least 324 (84%) of the 386 patients. Statistical analyses were performed to assess the efficacy of CMF treatment for the subgroups defined by HER2 and the status of other variables using a Bayesian approach. The end points considered were relapse-free survival (RFS) and cause-specific survival (CSS). RESULTS: Bayesian analysis of the treatment effect for HER2 and other variables indicated a clinical benefit from CMF treatment in all subgroups defined according to variables status. In particular regarding HER2 status, Bayesian estimates of RFS hazard ratios were equal to 0.484 and 0.641 and estimates of CSS hazard ratios were equal to 0.495 and 0.730 for HER2-positive and -negative tumors, respectively. CONCLUSION: CMF treatment showed a clinical benefit in the considered subgroups, defined according to HER2 and other tumor variables status. Patients with HER2-positive or HER2-negative tumors benefit from CMF treatment, and the poor prognosis associated with the HER2 overexpression in the untreated group could be completely overcome by the chemotherapy treatment. PMID- 11208824 TI - Efficacy of docetaxel 60 mg/m2 in patients with metastatic breast cancer according to the status of anthracycline resistance. AB - PURPOSE: To evaluate the efficacy of docetaxel 60 mg/m2 in metastatic breast cancer (MBC) according to the status of anthracycline resistance. PATIENTS AND METHODS: Ninety-nine patients with anthracycline-resistant MBC were treated with docetaxel 60 mg/m2 intravenously for a 90-minute period every 3 to 4 weeks. Anthracycline resistance was defined as primary and secondary resistance. Primary resistance was defined as progression during or within 6 months after completion of adjuvant anthracycline, and no MBC response to a first-line regimen that contained anthracycline. Secondary resistance was defined as progression after a documented clinical response to a first-line anthracycline treatment for MBC. Secondary resistance was further divided into three categories: (1) absolute resistance, or progression during treatment with anthracycline after a period of response; (2) relative resistance, or progression within 6 months after anthracycline administration ended; and (3) sensitive regrowth, or progression more than 6 months after the conclusion of anthracycline administration. RESULTS: The response rate in the 99 patients was 35.4% (95% confidence interval, 30.1% to 44.8%). The response rates according to the status of anthracycline resistance were as follows: primary resistance (n = 46), 19.6%; secondary resistance (n = 53), 49.1% (absolute resistance [n = 16], 56.3%); relative resistance (n = 17), 47.1%; and sensitive regrowth (n = 20), 45.0%. The median time to treatment failure in patients with primary resistance was 2.9 months, compared with 5.2 months in patients with secondary resistance (P = .0022). CONCLUSION: Docetaxel at a dose of 60 mg/m2 seemed to be effective in MBC with secondary resistance to anthracycline. The status of anthracycline resistance is important for the prediction of response to second-line treatment with docetaxel. PMID- 11208825 TI - Combined tamoxifen and luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer: a meta analysis of four randomized trials. AB - PURPOSE: The logic behind the application of luteinizing hormone-releasing hormone (LHRH) agonists in combination with tamoxifen in premenopausal women is that LHRH agonists on the one hand suppress the tamoxifen-induced stimulation of the pituitary-ovarian function and, on the other hand, seem as effective as surgical castration. This meta-analysis combines all randomized evidence to compare the combined treatment with LHRH agonist alone with respect to overall survival, progression-free survival, and objective response in premenopausal women with advanced breast cancer. PATIENTS AND METHODS: Four clinical trials randomizing a total of 506 premenopausal women with advanced breast cancer to LHRH agonist alone or to the combined treatment of LHRH agonist plus tamoxifen were identified. Meta-analytic techniques were used to analyze individual patient data from these trials. RESULTS: With a median follow-up of 6.8 years, there was a significant survival benefit (stratified log-rank test, P = .02; hazards ratio [HR] = 0.78) and progression-free survival benefit (stratified log-rank test, P = .0003; HR = 0.70) in favor of the combined treatment. The overall response rate was significantly higher on combined endocrine treatment (stratified Mantel Haenszel test, P = .03; odds ratio = 0.67). CONCLUSION: The combination of LHRH agonist plus tamoxifen is superior to LHRH agonist alone in premenopausal women with advanced breast cancer. Therefore, if a premenopausal woman with advanced breast cancer is thought to be suitable for endocrine treatment, it is proposed that the combination of a LHRH agonist plus tamoxifen be considered as the new standard treatment. PMID- 11208826 TI - Her-2/neu analysis in archival tissue samples of human breast cancer: comparison of immunohistochemistry and fluorescence in situ hybridization. AB - PURPOSE: The objective of our study was to compare the methods used in the literature to analyze HER-2/neu status on archival breast cancer tissue. Therefore, a series of antibodies was evaluated to assess their immunohistochemical (IHC) sensitivity in correlation to gene amplification determined by fluorescence in situ hybridization (FISH). MATERIALS AND METHODS: HER-2/neu overexpression was studied on paraffin sections of 85 invasive breast cancers using a panel of five monoclonal (9G6, 3B5, CB11, TAB250, GSF-HER2) and two polyclonal antibodies (A8010, A0485) in addition to the HercepTest (DAKO, Glostrup, Denmark). HER-2/neu gene amplification was determined by FISH using a dual-color probe (PathVysion; Vysis, Stuttgart-Fasanenhof, Germany). RESULTS: HER 2/neu overexpression was demonstrated in 26% (9G6, TAB250, GSF-HER2), 27% (3B5, CB11), 33% (A8010) and 42% (A0485, HercepTest) of the tumors. FISH on paraffin sections identified gene amplification in 28% of the tumors. Strongly positive IHC results (3+) were always associated with gene amplification. Among the 16 tumors presented with weakly positive IHC results (2+) using the HercepTest, 12 (75%) lacked gene amplification. CONCLUSION: The comparison of IHC and FISH demonstrated an excellent correlation of high-level HER-2/neu overexpression (3+) with gene amplification; ie, FISH does not provide further information in these tumors. However, weakly positive IHC results (2+) obtained with the HercepTest share only a minor association with gene amplification. PMID- 11208827 TI - Tamoxifen in the treatment of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. AB - PURPOSE: In two large Gynecologic Oncology Group studies of patients with advanced or recurrent endometrial carcinoma and no previous systemic therapy, progestins have demonstrated activity against advanced or recurrent endometrial carcinoma with response rates between 15% and 25%. Tamoxifen has been reported as variously active or inactive with or without previous systemic therapy. The purpose of this study was to determine whether tamoxifen exhibits enough activity in patients with advanced or recurrent endometrial carcinoma, who have not received systemic therapy, to warrant a phase III trial. PATIENTS AND METHODS: Sixty-eight eligible patients with advanced or recurrent endometrial carcinoma received oral tamoxifen 20 mg bid until toxicity was unacceptable or disease progressed. RESULTS: Three complete (4%) and four partial (6%) responses were observed for an overall response rate of 10% (90% confidence interval [CI], 5.7% to 17.9%). Patients with tumors that were more anaplastic tended to respond less frequently. The median progression-free survival for all 68 eligible patients was 1.9 months (90% CI, 1.7 to 3.2 months). The median survival was 8.8 months (90% CI, 7.0 to 10.1 months). CONCLUSION: Tamoxifen demonstrated modest activity at best against endometrial carcinoma and does not warrant further investigation as a single agent for this disease. Ongoing trials will assess the sequential use of tamoxifen and progestational agents. PMID- 11208828 TI - Occult tumor cells in bone marrow of patients with locoregionally restricted ovarian cancer predict early distant metastatic relapse. AB - PURPOSE: Based on conventional tumor staging, primary ovarian cancer is viewed as an intraperitoneal disease that rarely spreads to extraperitoneal organs. However, autopsy studies reveal a much higher rate of occult metastasis, indicating that extraperitoneal spread occurs with much greater frequency than previously appreciated. Consequently, we investigated the incidence of early hematogenous dissemination and its association with distant disease-free and overall survival. PATIENTS AND METHODS: Bone marrow aspirates from 108 patients newly diagnosed with International Federation of Gynecology and Obstetrics stage I to III ovarian cancer were prospectively analyzed with the novel anti cytokeratin (CK) antibody A45-B/B3. We investigated the frequency of CK-positive tumor cells in bone marrow and their effect on prognosis in relation to established risk factors for tumor progression. RESULTS: Tumor cells in bone marrow were detected in 32 (30%) of 108 patients. A CK-positive finding was unrelated to established risk parameters, except for poor nuclear grading of the primary tumor. At a median follow-up of 45 months (range, 12 to 77 months), the presence of occult metastatic cells in bone marrow was associated with the occurrence of clinically overt, extraperitoneal (predominantly extraskeletal) distant metastasis (relative risk [RR], 16.5; 95% confidence interval [CI], 6.2 to 56.9; P < .0001) and death from cancer-related causes (RR, 2.3; 95% CI, 1.2 to 4.3; P = .01). Multivariate analysis identified a positive bone marrow finding as an independent prognostic factor of reduced distant disease-free survival for all patients (RR, 13.8; 95% CI, 5.4 to 52.9; P < .0001) and for the 64 stage R0-1 patients (RR, 7.3; 95% CI, 1.5 to 56.8; P = .0021). CONCLUSION: Our data signal that hematogenous dissemination of tumor cells occurs early and throughout all stages of ovarian cancer. The clinical significance of our findings is supported by the unfavorable prognosis in association with the presence of occult metastatic cells, especially in those patients who received an effective locoregional therapy. PMID- 11208830 TI - Phase II study of rituximab in combination with chop chemotherapy in patients with previously untreated, aggressive non-Hodgkin's lymphoma. AB - PURPOSE: To determine the safety and efficacy of the combination of the chimeric anti-CD20 antibody Rituxan (rituximab, IDEC-C2B8; Genentech Inc, South San Francisco, CA) and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy in patients with aggressive non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Thirty-three patients with previously untreated advanced aggressive B-cell NHL received six infusions of Rituxan (375 mg/m2 per dose) on day 1 of each cycle in combination with six doses of CHOP chemotherapy given on day 3 of each cycle. RESULTS: The ORR by investigator assessment confirmed by the sponsor was 94% (31 of 33 patients). Twenty patients experienced a complete response (CR) (61%), 11 patients had a partial response (PR) (33%), and two patients were classified as having progressive disease. In the 18 patients with an International Prognostic Index (IPI) score > or = 2, the combination of Rituxan plus CHOP achieved an ORR of 89% and CR of 56%. The median duration of response and time to progression had not been reached after a median observation time of 26 months. Twenty-nine of 31 responding patients remained in remission during this follow-up period, including 15 of 16 patients with an IPI score > or = 2. The most frequent adverse events attributed to Rituxan were fever and chills, primarily during the first infusion. Rituxan did not seem to compromise the ability of patients to tolerate CHOP; all patients completed the entire six courses of the combination. The bcl-2 translocation of blood or bone marrow was positive at baseline in 13 patients; 11 patients had follow-up specimens obtained (eight CR, three PR), and all had a negative bcl-2 status after therapy. Only one patient has reconverted to bcl-2 positivity, and all patients remain in clinical remission. CONCLUSION: This is the first report to demonstrate the safety and efficacy of the Rituxan chimeric anti-CD20 antibody in combination with standard dose CHOP in the treatment of aggressive B-cell lymphoma. The clinical responses are at least comparable to those achieved with CHOP alone with no significant added toxicity. The presence or absence of the bcl-2 translocation did not affect the ability of patients to achieve a CR with this regimen. The ability to achieve sustained remissions in patients with an IPI score > or = 2 warrants further investigation with a randomized study. PMID- 11208829 TI - Pivotal phase III trial of two dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma. AB - PURPOSE: The objective of this phase III study was to determine the efficacy, safety, and pharmacokinetics of denileukin diftitox (DAB389IL-2, Ontak [Ligand Pharmaceuticals Inc, San Diego, CA]) in patients with stage Ib to IVa cutaneous T cell lymphoma (CTCL) who have previously received other therapeutic interventions. PATIENTS AND METHODS: Patients with biopsy-proven CTCL that expressed CD25 on > or = 20% of lymphocytes were assigned to one of two dose levels (9 or 18 microg/kg/d) of denileukin diftitox administered 5 consecutive days every 3 weeks for up to 8 cycles. Patients were monitored for toxicity and clinical efficacy, the latter assessed by changes in disease burden and quality of life measurements. Antibody levels of antidenileukin diftitox and anti interleukin-2 and serum concentrations of denileukin diftitox were also measured. RESULTS: Overall, 30% of the 71 patients with CTCL treated with denileukin diftitox had an objective response (20% partial response; 10% complete response). The response rate and duration of response based on the time of the first dose of study drug for all responders (median of 6.9 months with a range of 2.7 to more than 46.1 months) were not statistically different between the two doses. Adverse events consisted of flu-like symptoms (fever/chills, nausea/vomiting, and myalgias/arthralgias), acute infusion-related events (hypotension, dyspnea, chest pain, and back pain), and a vascular leak syndrome (hypotension, hypoalbuminemia, edema). In addition, 61% of the patients experienced transient elevations of hepatic transaminase levels with 17% grade 3 or 4. Hypoalbuminemia occurred in 79%, including 15% with grade 3 or 4 changes. Tolerability at 9 and 18 microg/kg/d was similar, and there was no evidence of cumulative toxicity. CONCLUSION: Denileukin diftitox has been shown to be a useful and important agent in the treatment of patients whose CTCL is persistent or recurrent despite other therapeutic interventions. PMID- 11208831 TI - Primary cutaneous non-Hodgkin's lymphoma of Ann Arbor stage I: preferential cutaneous relapses but high cure rate with doxorubicin-based therapy. AB - PURPOSE: Establish frequency, presenting features, response and relapse patterns, and outcome of primary cutaneous non-Hodgkin's lymphoma (PCNHL). PATIENTS AND METHODS: Review of untreated patients, older than 16 years, presenting between 1971 and 1993 with cutaneous lymphoma, not mycosis fungoides, and Ann Arbor stage I. RESULTS: We identified 46 patients, 27 males, with median age of 57 years. Treatment was radiotherapy in 10 patients, doxorubicin-based therapy in 33 patients that was followed by radiotherapy in 25 patients, and other combination with radiotherapy in one patient. The complete response rate was 95%. After a median follow-up of 140 months (range, 61 to 284 months), 18 patients have relapsed, and 14 have died from lymphoma. The first failure was exclusively cutaneous in 50% of relapses. For the 44 treated patients, progression-free survival (PFS; actuarial +/- SE) was 61% +/- 7% and survival was 58% +/- 9% at 12 years. For the 18 patients with diffuse large B-cell lymphoma, after doxorubicin based regimens, PFS was 71% +/- 12% (P = .0003) versus 0% after radiotherapy; survival was 77% +/- 12% versus 25% +/- 22% (P = 004), respectively. For the nine patients with follicular center-cell lymphoma treated with combined modality, the 12-year PFS was 89% +/- 11% and survival 70% +/- 18%. CONCLUSION: PCNHL is rare, and its first relapse is exclusively cutaneous in 50% of patients. Patients with diffuse large B-cell lymphoma are curable with doxorubicin-based regimens but not with radiotherapy. Prospective studies in PCNHL should define the cytogenetics, the basis for cutaneous tropism, the prognosis of histologic subtypes, and the role of radiotherapy. PMID- 11208832 TI - Autologous transplantation for diffuse aggressive non-Hodgkin's lymphoma in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry. AB - PURPOSE: To evaluate the results of high-dose chemotherapy and autologous hematopoietic stem-cell transplantation (autotransplants) in patients with diffuse aggressive non-Hodgkin's lymphoma (NHL) who never achieve a complete remission with conventional chemotherapy. PATIENTS AND METHODS: Detailed records from the Autologous Blood and Marrow Transplant Registry (ABMTR) on 184 patients with diffuse aggressive NHL who never achieved a complete remission with conventional chemotherapy and subsequently received an autotransplant were evaluated. Transplants were performed between 1989 and 1995 and were reported to the ABMTR by 48 centers in North and South America. RESULTS: Seventy-nine (44%) of 184 patients achieved a complete remission or a complete remission with residual imaging abnormalities of unknown significance after autotransplantation. Thirty-four (19%) of 184 had a partial remission and 55 (31%) of 184 had no response or progressive disease. Eleven patients (6%) were not assessable for response because of early death. The probabilities of progression-free and overall survival at 5 years after transplantation were 31% (95% confidence interval [CI], 24% to 38%) and 37% (95% CI, 30% to 45%), respectively. In multivariate analysis, chemotherapy resistance, Karnofsky performance status score less than 80 at transplantation, age > or = 55 years at transplantation, receiving three or more prior chemotherapy regimens, and not receiving pre- or posttransplant involved-field irradiation therapy were adverse prognostic factors for overall survival. CONCLUSION: High-dose chemotherapy and autologous hematopoietic stem-cell transplantation should be considered for patients with diffuse aggressive NHL who never achieve a complete remission but who are still chemotherapy-sensitive and are otherwise transplant candidates. PMID- 11208833 TI - Prognostic value of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose ([18F]FDG) after first-line chemotherapy in non-Hodgkin's lymphoma: is [18F]FDG-PET a valid alternative to conventional diagnostic methods? AB - PURPOSE: A complete remission (CR) after first-line therapy is associated with longer progression-free survival (PFS). However, defining CR is not always easy because of the presence of residual masses. Metabolic imaging with fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) offers the ability to differentiate between viable and fibrotic inactive tissue. In this study, we evaluated the value of PET in detecting residual disease and, hence, predicting relapse after first-line treatment in patients with non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Ninety-three patients with histologically proven NHL, who underwent a whole-body [18F]FDG-PET study after completion of first-line chemotherapy and who had follow-up of at least 1 year, were included. Persistence or absence of residual disease on PET was related to PFS using Kaplan Meier survival analysis. RESULTS: Sixty-seven patients showed a normal PET scan after first-line chemotherapy; 56 of 67 remained in CR, with a median follow-up of 653 days. Nine of these patients with a residual mass considered as unconfirmed CR received additional radiotherapy. Only 11 of 67 patients relapsed (median PFS, 404 days). Persistent abnormal [18F]FDG uptake was seen in 26 patients, and all of them relapsed (median PFS, 73 days). Because standard restaging also suggested residual disease, 12 patients received immediate secondary treatment. In 14 of 26 patients, only PET predicted persistent disease. From these patients, relapse was proven either by biopsy (n = 8) or by progressive disease on computed tomography or magnetic resonance imaging (n = 6). CONCLUSION: Persistent abnormal [18F]FDG uptake after first-line chemotherapy in NHL is highly predictive for residual or recurrent disease. In relapsing patients, PFS was significantly shorter after a positive scan than after a negative scan. PMID- 11208834 TI - Frequency of the Bcl-2/IgH rearrangement in normal individuals: implications for the monitoring of disease in patients with follicular lymphoma. AB - PURPOSE: To determine the incidence and frequency of the Bcl-2/IgH rearrangement in the peripheral blood of normal individuals to define the potential complication this may pose for the molecular monitoring of disease in patients with follicular lymphoma (FL). MATERIALS AND METHODS: The incidence and frequency of the major breakpoint cluster region rearrangement in DNA extracted from peripheral blood or lymphoblastoid cell lines from 481 normal individuals was determined using a TaqMan real-time polymerase chain reaction assay (PE Applied Biosystems, Foster City, CA). RESULTS: Twenty three percent of samples were positive for the Bcl-2/IgH rearrangement, with approximately 3% of these at levels of more than 1 in 10(4) cells. CONCLUSION: The presence of circulating Bcl 2/IgH+ cells, other than those derived from the malignant clone, could confound the detection and quantitation of minimal residual disease in patients with FL, particularly at low levels of tumor burden. PMID- 11208835 TI - Interferon adjuvant to radical nephrectomy in Robson stages II and III renal cell carcinoma: a multicentric randomized study. AB - PURPOSE: Because interferon gave promising results in the management of metastatic renal cell carcinoma in the 1980s, a multicentric randomized controlled trial was planned to compare adjuvant recombinant interferon alfa-2b (rIFNalpha2b) with observation after radical nephrectomy in patients with Robson stages II and III renal cell carcinoma. Overall and event-free survival were to be evaluated together with prognostic factors. PATIENTS AND METHODS: Overall and event-free survival curves for 247 patients (124 controls and 123 treated) were estimated by the Kaplan-Meier method and compared using the log-rank test. Cox's multiple regression models were adopted to perform a joint analysis of treatment and prognostic factors. RESULTS: The 5-year overall and event-free survival probabilities were 0.665 and 0.671, respectively, for controls and 0.660 and 0.567, respectively, for the treated group; the differences were not statistically significant (2P = .861 for overall and 2P = .107 for event-free survival with the log-rank test). Regarding prognostic factors, only grade, pT, and pN demonstrated a significant prognostic role. First-order interactions of treatment with pT and pN category were investigated; a significant interaction was found between pN and treatment. A harmful effect of rIFNalpha2b in the 97 treated pN0 patients and a protective effect in the 13 treated pN2/pN3 patients were statistically significant. CONCLUSION: Adjuvant rIFNalpha2b is not indicated after radical nephrectomy for renal cell carcinoma. The protective effect in the small group of pN2/pN3 patients requires further investigation. PMID- 11208836 TI - Vascular endothelial growth factor 189 mRNA isoform expression specifically correlates with tumor angiogenesis, patient survival, and postoperative relapse in non-small-cell lung cancer. AB - PURPOSE: The purpose of this study was to evaluate the correlation between the expression of four different vascular endothelial growth factor (VEGF) mRNA isoforms (VEGF121, VEGF165, VEGF 189, and VEGF206) and the clinicopathologic characteristics, tumor angiogenesis, and outcome of patients with non-small-cell lung cancer. PATIENTS AND METHODS: We examined the expression of four different VEGF mRNA isoforms in 57 non-small-cell lung cancers using reverse transcriptase polymerase chain reaction and the tumor angiogenesis using immunohistochemical staining. RESULTS: All 57 lung cancer samples expressed the VEGF121, VEGF165, and VEGF189 mRNA isoforms, and three expressed the VEGF206 mRNA isoform. A high tumoral VEGF189 mRNA isoform expression ratio was associated with a high intratumoral microvessel count (P = .013), short survival (< 24 months; P = .001), and early postoperative relapse (< 12 months; P = .001). Survival and postoperative relapse time were significantly shorter in patients with a high compared with a low tumor VEGF189 mRNA isoform expression ratio (P = .0001 and P = .0086, respectively, log-rank test). In contrast, the VEGF165 and VEGF 206 mRNA isoform expression ratios showed no statistical correlation with tumor angiogenesis, postoperative relapse time, or survival. A high VEGF121 mRNA isoform expression ratio was associated with short survival (< 24 months) and early relapse (< 12 months). Multivariate analysis showed that VEGF 189 mRNA isoform expression, microvessel count, and nodal status were the most important independent prognostic factors for patient survival and postoperation recurrence. CONCLUSION: The VEGF189 mRNA isoform expression ratio shows a greater correlation with tumor angiogenesis, postoperative relapse time, and survival than do the expression ratios for the VEGF121, VEGF165, and VEGF206 mRNA isoforms and can be used as a prognostic indicator for patients with non-small-cell lung cancers. PMID- 11208838 TI - Lack of prognostic significance of p53 and K-ras mutations in primary resected non-small-cell lung cancer on E4592: a Laboratory Ancillary Study on an Eastern Cooperative Oncology Group Prospective Randomized Trial of Postoperative Adjuvant Therapy. AB - PURPOSE: To determine the prognostic and predictive significance of p53 and K-ras mutations in patients with completely resected non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were randomized preoperatively to receive adjuvant postoperative radiotherapy (Arm A) or radiotherapy plus concurrent chemotherapy (Arm B). p53 protein expression was studied by immunohistochemistry (IHC) and p53 mutations in exons 5 to 8 were evaluated by single-strand conformational analysis. K-ras mutations in codons 12, 13, and 61 were determined using engineered restriction fragment length polymorphisms. RESULTS: Four hundred eighty-eight patients were entered onto E3590; 197 tumors were assessable for analysis. Neither presence nor absence of p53 mutations, p53 protein expression, or K-ras mutations correlated with survival or progression-free survival. There was a trend toward improved survival for patients with wildtype K-ras (median, 42 months) compared with survival of patients with mutant K-ras who were randomized to chemotherapy plus radiotherapy (median, 25 months; P = .09). Multivariate analysis revealed only age and tumor stage to be significant prognostic factors, although there was a trend bordering on statistical significance for K-ras (P = .066). Analysis of survival difference by p53 by single-stranded conformational polymorphism and IHC, interaction of p53 and K-ras, interaction of p53 and treatment arm, nodal station, extent of surgery, weight loss, and histology did not reach statistical significance. CONCLUSION: p53 mutations and protein overexpression are not significant prognostic or predictive factors in resected stage II or IIIA NSCLC. K-ras mutations may be a weak prognostic marker. p53 or K ras should not be routinely used in the clinical management of these patients. PMID- 11208837 TI - Twice-weekly paclitaxel and weekly carboplatin with concurrent thoracic radiation followed by carboplatin/paclitaxel consolidation for stage III non-small-cell lung cancer: a California Cancer Consortium phase II trial. AB - PURPOSE: Recent studies have suggested the superiority of concurrent chemoradiotherapy and the efficacy of paclitaxel/carboplatin in advanced non small-cell lung cancer (NSCLC). In view of those results, we sought to examine the safety and efficacy of administration of radiosensitizing paclitaxel twice weekly and carboplatin weekly with concurrent thoracic radiation therapy (XRT) followed by consolidation paclitaxel and carboplatin for stage III NSCLC in a multi-institutional phase II trial. PATIENTS AND METHODS: Induction chemoradiotherapy consisted of paclitaxel 30 mg/m2 delivered intravenously (IV) for 1 hour twice weekly for 6 weeks, carboplatin at a dose based on an area under the concentration-time curve (AUC) of 1.5 mg/mL x min, given IV once weekly for 6 weeks, and concomitant XRT of 1.8 to 2.0 Gy daily for a total of 61 Gy. Patients who achieved a complete response, partial response, or stable disease received two 21-day cycles of consolidation chemotherapy consisting of paclitaxel 200 mg/m2 IV for 3 hours and carboplatin at a dose based on an AUC of 6 mg/mL x min. RESULTS: Thirty-four patients were eligible. Their median age was 62 years (range, 39 to 73 years), 59% were female, 41% were male, 94% had a performance status of 0 or 1, 38% had stage IIIA NSCLC, and 62% had stage IIIB NSCLC. Common grade III and IV toxicities during the induction chemoradiation phase included esophagitis (38%) and neutropenia (12%). The most common adverse reaction during consolidation chemotherapy was grade III neutropenia in five patients (15%). The overall response rate was 71%, which was achieved in the induction phase. The median follow-up was 20 months, the median survival was 17 months, and 2-year actuarial survival rate was 40% (95% confidence interval, 20% to 65%). CONCLUSION: This regimen is tolerable and results are promising. We recommend further evaluation of this regimen in a phase III trial. PMID- 11208839 TI - Phase I/II study of escalating doses of vinorelbine in combination with oxaliplatin in patients with advanced non-small-cell lung cancer. AB - PURPOSE: Oxaliplatin is a platinum compound active in non-small-cell lung cancer (NSCLC) patients, and vinorelbine (VNB) is an active reference agent. This phase I/II study was performed to determine the dose-limiting toxicity (DLT), the maximum-tolerated dose (MTD), and the recommended dose (RD) of a VNB/oxaliplatin combination given to previously untreated patients with advanced NSCLC. PATIENTS AND METHODS: Oxaliplatin was given at the fixed dose of 130 mg/m2 (2-hour intravenous [IV] infusion) on day 1. VNB was administered on days 1 and 8 (10 minute IV infusion), with doses starting at 22 mg/m2/d and escalated by 2 mg/m2 increments until MTD. Treatment was repeated every 3 weeks. No special hydration measures or prophylactic granulocyte colony-stimulating factors were used. RESULTS: Twenty-seven patients (20 men, 7 women) received 110 cycles total at six different VNB dose levels. Neutropenia was the DLT. Although no patient experienced DLT at the highest dose level (32 mg/m2/d), multiple treatment delays (54% of cycles) and dose reductions (34% of cycles) were required at this dose level. Others toxicities were mainly limited to grade 1 peripheral neuropathy and grade 1/2 nausea/vomiting. The relative dose-intensity of administered VNB from dose levels 3 to 6 (26 to 32 mg/m2) remained stable, whereas grade 3/4 neutropenia increased. All patients were assessable for activity; there were 10 objective responses, including one complete response (37% response rate). CONCLUSION: The present combination can be safely administered in an outpatient setting. The RD is VNB 26 mg/m2 days 1 and 8 with oxaliplatin 130 mg/m2 day 1 every 3 weeks. PMID- 11208840 TI - Solid cancers after bone marrow transplantation. AB - PURPOSE: To evaluate the incidence and associated risk factors of solid cancers after bone marrow transplantation (BMT). PATIENTS AND METHODS: We analyzed 2,129 patients who had undergone BMT for hematologic malignancies at the City of Hope National Medical Center between 1976 and 1998. A retrospective cohort and nested case-control study design were used to evaluate the role of pretransplantation therapeutic exposures and transplant conditioning regimens. RESULTS: Twenty-nine patients developed solid cancers after BMT, which represents a two-fold increase in risk compared with a comparable normal population. The estimated cumulative probability (+/- SE) for development of a solid cancer was 6.1% +/- 1.6% at 10 years. The risk was significantly elevated for liver cancer (standardized incidence ratio [SIR], 27.7; 95% confidence interval [CI], 1.9 to 57.3), cancer of the oral cavity (SIR, 17.4; 95% CI, 6.3 to 34.1), and cervical cancer (SIR, 13.3; 95% CI, 3.5 to 29.6). Each of the two patients with liver cancer had a history of chronic hepatitis C infection. All six patients with squamous cell carcinoma of the skin had chronic graft-versus-host disease. The risk was significantly higher for survivors who were younger than 34 years of age at time of BMT (SIR, 5.3; 95% CI, 2.7 to 8.6). Cancers of the thyroid gland, liver, and oral cavity occurred primarily among patients who received total-body irradiation. CONCLUSION: The risk of radiation-associated solid tumor development after BMT is likely to increase with longer follow-up. This underscores the importance of close monitoring of patients who undergo BMT. PMID- 11208841 TI - Risks of young age for selected neurocognitive deficits in medulloblastoma are associated with white matter loss. AB - PURPOSE: To test the hypothesis that inadequate development of normal-appearing white matter (NAWM) is associated with the relationship between young age at the time of craniospinal irradiation (CRT) and deficient neurocognitive performance in survivors of childhood medulloblastoma. PATIENTS AND METHODS: Forty-two patients treated since 1985 participated in this cross-sectional study. All had been treated with CRT with or without chemotherapy and had survived 1 or more years after treatment. Neurocognitive evaluations were conducted with tests of intellect (intelligent quotient; IQ), verbal memory, and sustained attention. Quantitative magnetic resonance imaging, using a hybrid neural network, assessed the volume of NAWM. RESULTS: Neurocognitive test results were below normal expectations for age at the time of testing. A young age at CRT was significantly associated with worse performance on all neurocognitive tests except that of verbal memory. An increased time from completion of CRT was significantly associated with worse performance on all neurocognitive tests except that of sustained attention. After statistically controlling for the effects of time from CRT, we examined the association of NAWM with neurocognitive test results. These analyses revealed that NAWM accounted for a significant amount of the association between age at CRT and IQ, factual knowledge, and verbal and nonverbal thinking, but not sustained attention or verbal memory. CONCLUSION: The present results suggest that, at least for some cognitive functions, deficient development and/or loss of NAWM after CRT may provide a neuroanatomical substrate for the adverse impact of a young age at the time of CRT. PMID- 11208842 TI - Growth hormone replacement therapy in children with medulloblastoma: use and effect on tumor control. AB - PURPOSE: Progress has been made in the treatment of medulloblastoma, the most common childhood malignant brain tumor: However, many long-term survivors will have posttherapy growth hormone insufficiency with resultant linear growth retardation. Growth hormone replacement therapy (GHRT) may significantly improve growth, but there is often reluctance to initiate GHRT because of concerns of an increased likelihood of tumor relapse. PATIENTS AND METHODS: This study retrospectively reviewed the use of GHRT for survivors of medulloblastoma in 11 neuro-oncology centers in North America who received initial treatment for disease between 1980 and 1993 to determine its impact on disease control. A Landmark analysis was used to evaluate the relative risk of relapse in surviving patients. RESULTS: Five hundred forty-five consecutive patients less than 15 years of age at diagnosis were identified. Six-year progression-free survival (mean +/- SD) was 40% +/- 5% in children less than 3 years of age at diagnosis compared with 59% +/- 3% for older patients. Older patients with total or near total resections (P = .003) and localized disease at diagnosis (P < .0001) had the highest likelihood of survival. One hundred seventy patients (33% +/- 3% of the cohort) received GHRT. GHRT use varied widely among institutions, ranging from 5% to 73%. GHRT was begun a mean of 3.9 years after diagnosis, later in children younger than 3 years at diagnosis (5.4 years). By Landmark analyses, for those surviving 2, 3, and 5 years after diagnosis, there was no evidence that GHRT increased the rate of disease relapse. CONCLUSION: This large retrospective review demonstrates that GHRT is underutilized in survivors of medulloblastoma and is used relatively late in the course of the illness. GHRT is not associated with an increased likelihood of disease relapse. PMID- 11208843 TI - Optimal duration of preoperative therapy in unilateral and nonmetastatic Wilms' tumor in children older than 6 months: results of the Ninth International Society of Pediatric Oncology Wilms' Tumor Trial and Study. AB - PURPOSE: To determine the optimal duration of preoperative chemotherapy to further increase the proportion of stage I tumors by comparison of two regimens in the treatment of patients older than 6 months who have unilateral Wilms' tumor. PATIENTS AND METHODS: Eligible patients (n = 382) initially received four weekly doses of vincristine (VCR) and two courses of actinomycin D (AMD) and were randomized either to be operated on (4-week group [n = 193]) or to receive 4 more weeks of the same chemotherapy regimen (8-week group [n = 189]). The assessment criterion was the observed percentage of stage I tumors. After surgery, patients were assigned according to tumor stage and histology to four different treatment groups: stage I and favorable histology (n = 5) were to have no further treatment (NFT); stage I and standard histology or anaplasia (n = 244), VCR and AMD for 17 weeks (AV); stages II and III and favorable or standard histology, VCR, AMD, and an anthracycline for 27 weeks (AVE) with no abdominal radiotherapy for stage II N0 disease (n = 75) or with a 15-Gy dose of abdominal irradiation (RTH) in case of stages IIN1 and III (n = 56). Anaplastic tumors staged higher than I or clear cell sarcoma of the kidney (14), AMD, VCR, an anthracycline, and ifosfamide for 36 weeks (DEVI). RESULTS: No advantage was found in favor of prolonged preoperative treatment. The percentages obtained for the 4-week and the 8-week groups, respectively, were as follows: stage I, 64% versus 62%; intraoperative tumor rupture rate, 1% versus 3%; 2-year EFS, 84% versus 83%; and 5-year OS, 92% versus 87%. Two-year EFS and 5-year OS rates, respectively, of the different treatment groups were as follows: NFT, 100% for both EFS and OS; AV, 88% and 93%; AVE, 84% and 88%; AVE RTH, 71% and 85%; and DEVI, 71% and 71%. The rate of abdominal recurrences in stage II N0 nonirradiated patients was 6.6%. CONCLUSION: The 4-week schedule pre-nephrectomy chemotherapy regimen should be considered the standard treatment. Clinical trials should continue to improve the cure rate of high-risk patients and the quality of life of children with a more favorable prognosis. PMID- 11208844 TI - Feasibility of quantitative pain assessment in outpatient oncology practice. AB - PURPOSE: Although physicians view failure to assess pain systematically as the most important barrier to outpatient cancer pain management, little is known about pain assessment in this setting. We sought to determine whether pain is routinely assessed and whether routine quantitative pain assessment is feasible in a busy outpatient oncology practice. PATIENTS AND METHODS: We conducted a pre- and postintervention chart review of 520 randomly selected medical and radiation oncology patient visits at a community hospital-based private outpatient practice. The intervention consisted of training health assistants (HAs) to measure and document patient pain scores by using a visual analog scale. The main outcome measures included HA documentation of patient pain scores, quantitative and qualitative mention of pain in the physician note, and analgesic treatment before and after the intervention. RESULTS: After the intervention, HA documentation of pain scores increased from 1% to 75.6% (P < .0001). Physician documentation increased from 0% to 4.8% for quantitative documentation (P < .01), and from 60.0% to 68.3% for qualitative documentation (not significant). Of all the patients, 23.1% reported significant pain. Subgroups with greater pain included patients actively receiving radiation treatments and patients with lung cancer. Of patients with significant pain, 28.2% had no mention of pain in the physician note and 47.9% had no documented analgesic treatment. CONCLUSION: Quantitative pain assessment was virtually absent before our intervention but easily implemented and sustained in a busy outpatient oncology practice. Pain score collection identified a high prevalence of pain, patient subgroups at risk for pain, and a significant proportion of patients with pain that was neither evaluated nor treated by their oncologists. PMID- 11208845 TI - Randomized trial of procarbazine, lomustine, and vincristine in the adjuvant treatment of high-grade astrocytoma: a Medical Research Council trial. AB - PURPOSE: Meta-analyses of the published literature suggest a survival benefit to adjuvant chemotherapy for high-grade astrocytoma, which individual small trials have been unable to demonstrate reliably. The Medical Research Council Brain Tumour Working Party initiated the largest randomized trial of adjuvant chemotherapy for glioma in an attempt to provide a definitive answer. PATIENTS AND METHODS: After surgery, patients aged < or = 70 years, with World Health Organization grade 3 or 4 astrocytoma, were randomized to radiotherapy alone (RT) or RT plus procarbazine, lomustine, and vincristine (PCV) chemotherapy (RT-PCV) given at 6-week intervals to a maximum of 12 courses (procarbazine 100 mg/m2 days 1 to 10, lomustine 100 mg/m2 day 1, and vincristine 1.5 mg/m2 (max 2 mg) day 1). A neuropathology panel independently reviewed all cases. To reliably detect a 10% increase in 2-year survival (from 15% to 25%), 600 patients were required. RESULTS: Between September 1988 and May 1997, 15 United Kingdom centers randomized 674 patients (RT = 339 patients; RT-PCV = 335 patients). With a median follow-up for survivors of 3 years, 617 patients have died, (RT = 310 patients; RT-PCV = 307 patients). Median survival was 9.5 months for RT and 10 months for RT-PCV (hazard ratio = 0.95; 95% confidence interval, 0.81 to 1.11; log-rank P = .50). Tests for interaction revealed no significant differences in treatment effect according to tumor grade, age, performance status, or extent of neurosurgery. CONCLUSION: This trial shows no benefit to PCV chemotherapy, and current data exclude an increase in median survival of more than 10 weeks and in a 1- or 2-year survival rate of more than 7% to 8%. This suggests that no chemotherapy control arms remain ethical in randomized trials in high-grade astrocytoma. PMID- 11208846 TI - Phase I and pharmacokinetic study of photodynamic therapy for high-grade gliomas using a novel boronated porphyrin. AB - PURPOSE: To determine the recommended dose, toxicity profile, and pharmacokinetics of a novel boronated porphyrin (BOPP) for photodynamic therapy (PDT) of intracranial tumors. PATIENTS AND METHODS: BOPP was administered alone in increasing doses (0.25, 0.5, 1.0, 2.0, 4.0, or 8.0 mg/kg) preoperatively in patients with intracranial tumors undergoing postresection PDT until dose limiting toxicity (DLT) was observed. RESULTS: Twenty-nine assessable patients with intracranial tumors received BOPP intravenously 24 hours before surgery. The recommended dose was 4 mg/kg. Dose escalation was limited by thrombocytopenia. The most common nonhematologic toxicity was skin photosensitivity. Pharmacokinetic parameters showed increased area under the plasma concentration time curve and maximum concentration with increased dose. Tumor BOPP concentrations also increased with increased dose. CONCLUSION: BOPP at a dose of 4 mg/kg was well tolerated. DLT was thrombocytopenia, and photosensitivity was the only other toxicity of note. The efficacy of PDT using BOPP requires further exploration. PMID- 11208847 TI - Prognostic factors in localized primary synovial sarcoma: a multicenter study of 128 adult patients. AB - PURPOSE: To identify most significant and therapeutically relevant prognostic factors in adults with localized primary synovial sarcomas (SS) and to confirm the usefulness of the French Federation of Cancer Centers (FNCLCC) grading system, the prognostic impact of which has been already proven in soft tissue sarcomas. PATIENTS AND METHODS: Data on 128 patients with nonmetastatic SS collected from a cooperative database by the FNCLCC Sarcoma Group between 1980 and 1994 were studied retrospectively. Immunohistochemistry was performed at diagnosis in 77 cases (61%). The tumors were classified as biphasic (n = 45), monophasic fibrous (n = 72), and poorly differentiated (n = 10) subtypes. Histologic grade was determined according to the FNCLCC method, and vascular invasion was assessed in every case. RESULTS: The 5-year disease-specific survival (DSS) rate for this series of patients with localized SS was 62.9% (+/- 9.6% [SD]) with a median follow-up time of 37 months (range, 8 to 141 months). In multivariate analysis, the adverse risk factors associated with decreased DSS were International Union Against Cancer/American Joint Committee on Cancer stage III/IVA disease, male sex, and truncal tumor locations. For metastasis-free survival (MFS), disease stage III/IVA, tumor necrosis, and monophasic subtypes were the major factors associated with a less favorable prognosis. Separately, when not using disease stage, tumor necrosis, and mitotic activity, histologic grade became the most significant prognostic factor for both DSS and MFS. In addition, larger tumors and older patients become associated with a significantly worse prognosis. Independent adverse risk factors for local recurrence-free survival included histologic grade 3 and truncal tumor location. CONCLUSION: These data confirm that not all SS present the same severe outcome. High-risk patients identified on the basis of these parameters may qualify for an aggressive treatment approach. PMID- 11208848 TI - Phase I trial of concurrent tirapazamine, cisplatin, and radiotherapy in patients with advanced head and neck cancer. AB - PURPOSE: To determine the maximum-tolerated dose of tirapazamine when combined with cisplatin and radiation in patients with T3/4 and/or N2/3 squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: The starting schedule was conventionally fractionated radiotherapy (70 Gy in 7 weeks) with concomitant cisplatin 75 mg/m2 and tirapazamine 290 mg/m2 (before cisplatin) in weeks 1, 4, and 7 and tirapazamine alone 160 mg/m2 three times a week in weeks 2, 3, 5, and 6. Positron emission tomography scans for tumor hypoxia (18F misonidazole) were performed before and during radiotherapy. RESULTS: We treated 16 patients with predominantly oropharyngeal primary tumors, including 10 patients with T4 or N3 disease. Febrile neutropenia occurred toward the end of radiotherapy in three out of six patients treated on the initial dose level. Two of these patients also developed grade 4 acute radiation reactions. Another 10 patients were treated with the same doses, but the week 5 and week 6 tirapazamine doses were omitted. This resulted in less neutropenia and only one dose-limiting toxicity (DLT) (febrile neutropenia), and eight out of 10 patients completed treatment without any dose omissions. In these 10 patients, the acute radiation toxicities were not obviously enhanced compared with chemoradiotherapy regimens using concurrent platinum and fluorouracil. 18F misonidazole scans detected hypoxia in 14 of 15 patients at baseline, with only one patient having detectable hypoxia at the end of treatment. With a median follow-up of 2.7 years, the 3-year failure-free survival rate was 69% (SE, 12%), the 3-year local progression-free rate was 88% (SE, 8%), and the 3-year overall survival rate was 69% (SE, 12%). CONCLUSION: DLT was due unexpectedly to febrile neutropenia, which could be overcome by omitting tirapazamine in weeks 5 and 6. The combination of tirapazamine, cisplatin, and radiotherapy resulted in remarkably good and durable clinical responses in patients with very advanced head and neck cancers. It warrants further investigation. PMID- 11208849 TI - Can we predict radiation-induced changes in pulmonary function based on the sum of predicted regional dysfunction? AB - PURPOSE: To determine whether changes in whole-lung pulmonary function test (PFT) values are related to the sum of predicted radiation therapy (RT)-induced changes in regional lung perfusion. PATIENTS AND METHODS: Between 1991 and 1998, 96 patients (61% with lung cancer) who were receiving incidental partial lung irradiation were studied prospectively. The patients were assessed with pre- and post-RT PFTs (forced expiratory volume in one second [FEV1] and diffusion capacity for carbon monoxide [DLCO]) for at least a 6-month follow-up period, and patients were excluded if it was determined that intrathoracic recurrence had an impact on lung function. The maximal declines in PFT values were noted. A dose response model based on RT-induced reduction in regional perfusion (function) was used to predict regional dysfunction. The predicted decline in pulmonary function was calculated as the weighted sum of the predicted regional injuries: equation [see text] where Vd is the volume of lung irradiated to dose d, and Rd is the reduction in regional perfusion anticipated at dose d. RESULTS: The relationship between the predicted and measured reduction in PFT values was significant for uncorrected DLCO (P = .005) and borderline significant for DLCO (P = .06) and FEV1 (P = .08). However, the correlation coefficients were small (range,.18 to.30). In patients with lung cancer, the correlation coefficients improved as the number of follow-up evaluations increased (range,.43 to.60), especially when patients with hypoperfusion in the lung adjacent to a central mediastinal/hilar thoracic mass were excluded (range,.59 to.91). CONCLUSION: The sum of predicted RT-induced changes in regional perfusion is related to RT-induced changes in pulmonary function. In many patients, however, the percentage of variation explained is small, which renders accurate predictions difficult. PMID- 11208850 TI - Comparison of diameter and perimeter methods for tumor volume calculation. AB - PURPOSE: Lesion volume is often used as an end point in clinical trials of oncology therapy. We sought to compare the common method of using orthogonal diameters to estimate lesion volume (the diameter method) with a computer assisted planimetric technique (the perimeter method). METHODS: Radiologists reviewed 825 magnetic resonance imaging studies from 219 patients with glioblastoma multiforme. Each study had lesion volume independently estimated via the diameter and perimeter methods. Cystic areas were subtracted out or excluded from the outlined lesion. Inter- and intrareader variability was measured by using multiple readings on 48 cases. Where serial studies were available in noncystic cases, a mock response analysis was used. RESULTS: The perimeter method had a reduced interreader and intrareader variability compared with the diameter method (using SD of differences): intrareader, 1.76 mL v 7.38 mL (P < .001); interreader, 2.51 mL v 9.07 mL (P < .001) for perimeter and diameter results, respectively. Of the 121 noncystic cases, 23 had serial data. In six (26.1%) of those 23, a classification difference occurred when the perimeter method was used versus the diameter method. CONCLUSION: Variability of measurements was reduced with the computer-assisted perimeter method compared with the diameter method, which suggests that changes in volume can be detected more accurately with the perimeter method. The differences between these techniques seem large enough to have an impact on grading the response to therapy. PMID- 11208851 TI - Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. AB - PURPOSE: Two identical, concurrent, parallel, multicenter, randomized, double blind, double-dummy trials were conducted to compare the efficacy and safety of zoledronic acid and pamidronate for treating hypercalcemia of malignancy (HCM). PATIENTS AND METHODS: Patients with moderate to severe HCM (corrected serum calcium [CSC] > or = 3.00 mmol/L [12.0 mg/dL]) were treated with a single dose of zoledronic acid (4 or 8 mg) via 5-minute infusion or pamidronate (90 mg) via 2 hour infusion. A protocol-specified pooled analysis of the two parallel trials was performed. Clinical end points included rate of complete response by day 10, response duration, and time to relapse. RESULTS: Two hundred eighty-seven patients were randomized and evaluated for safety; 275 were evaluated for efficacy. Both doses of zoledronic acid were superior to pamidronate in the treatment of HCM. The complete response rates by day 10 were 88.4% (P = .002), 86.7% (P = .015), and 69.7% for zoledronic acid 4 mg and 8 mg and pamidronate 90 mg, respectively. Normalization of CSC occurred by day 4 in approximately 50% of patients treated with zoledronic acid and in only 33.3% of the pamidronate treated patients. The median duration of complete response favored zoledronic acid 4 and 8 mg over pamidronate 90 mg with response durations of 32, 43, and 18 days, respectively. CONCLUSION: Zoledronic acid is superior to pamidronate; 4 mg is the dose recommended for initial treatment of HCM and 8 mg for relapsed or refractory hypercalcemia. PMID- 11208852 TI - Melastatin expression and prognosis in cutaneous malignant melanoma. AB - PURPOSE: Melastatin (MLSN-1), a novel melanocyte-specific gene recently identified using a genomic approach, is expressed in murine and human melanoma cells at levels inversely proportional to metastatic rates in vivo. We studied the relationship between expression of melastatin mRNA in the primary cutaneous tumor and prognosis in patients with localized malignant melanoma. PATIENTS AND METHODS: Melastatin mRNA was evaluated by in situ hybridization in primary cutaneous melanoma from 150 patients with localized disease (American Joint Committee on Cancer [AJCC] stage I and II). Multivariate Cox proportional hazards regression analysis was performed to assess the prognostic utility of melastatin mRNA expression while adjusting for other prognostic indicators. RESULTS: Uniform melastatin mRNA expression in the primary tumor was correlated with prolonged disease-free survival (P < .0001). Multivariate analysis revealed that melastatin status, mitotic rate, and tumor thickness influence disease-free survival independently. The 8-year disease-free survival rate in AJCC stage I patients whose tumors diffusely expressed melastatin mRNA was 100%, whereas in stage I patients with melastatin loss, the disease-free survival rate was 77% +/- 15% (median +/- SE). In patients with stage II disease whose tumors diffusely expressed melastatin mRNA, the 8-year disease-free survival rate was 90% +/- 7%, whereas in patients with melastatin loss, the disease-free survival rate was 51% +/- 8%. CONCLUSION: Downregulation of melastatin mRNA in the primary cutaneous tumor is a prognostic marker for metastasis in patients with localized malignant melanoma and is independent of tumor thickness and other variables. Used in combination, melastatin status and tumor thickness allow for the identification of subgroups of patients at high and low risk of developing metastatic disease. PMID- 11208853 TI - Increased serum concentration of angiogenic factors in malignant melanoma patients correlates with tumor progression and survival. AB - PURPOSE: To determine the predictive value of the angiogenic serum factors angiogenin, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and interleukin-8 (IL-8) for the prognosis of patients with malignant melanoma. PATIENTS AND METHODS: Angiogenin, VEGF, bFGF, and IL-8 were measured in sera of 125 melanoma patients with different stages of disease and with or without current therapy including interferon alfa and different cytostatics in comparison with 30 healthy controls using enzyme-linked immunosorbent assay. RESULTS: Serum levels of angiogenin, VEGF, bFGF, and IL-8 were significantly increased in melanoma patients compared with healthy controls. Elevated serum concentrations of VEGF, bFGF, and IL-8 were associated with advanced disease stages and tumor burden. Cytostatic therapy of patients was accompanied by increased serum levels of angiogenin, bFGF, and IL-8. As shown by univariate analysis, elevated serum levels of VEGF (P = .0001 and .0036), bFGF (P < .00005 and < .00005), and IL-8 (P < .00005 and < .00005) were strongly correlated with a poor overall and progression-free survival, respectively. Multivariate analysis revealed stage of disease (P = .0238), tumor burden (P = .0347), VEGF (P = .0036), bFGF (P = .0252), and IL-8 (P = .0447) as independent predictive factors of overall survival. Tumor burden (P = .0081), VEGF (P = .0245), and IL-8 (P = .0089) were found as independent predictive factors of progression-free survival. CONCLUSION: Our data suggest that the angiogenic serum factors VEGF, bFGF, and IL-8 are useful predictive markers for overall and progression-free survival in melanoma patients. PMID- 11208854 TI - Phase I clinical trial of oral COL-3, a matrix metalloproteinase inhibitor, in patients with refractory metastatic cancer. AB - PURPOSE: This phase I clinical trial was designed to determine the maximum tolerated dose and dose-limiting toxicities of the matrix metalloproteinase (MMP) inhibitor COL-3 in patients with refractory solid tumors. PATIENTS AND METHODS: Thirty-five patients with different cancer types were enrolled. COL-3 doses were escalated from 36 mg/m2/d in successive cohorts of at least three patients. Circulating levels of MMP-2, MMP-9, vascular endothelial growth factor, and basic fibroblast growth factor were assessed during treatment. Pharmacokinetic parameters were assessed for single and multiple doses of drug. RESULTS: Cutaneous phototoxicity was dose-limiting at 98 mg/m2/d. With the use of prophylactic sunblock, COL-3 was well tolerated at 70 mg/m2/d. The dose of 36 mg/m2/d was well tolerated without the use of sunblock. Other toxicities that did not seem to be related to dose or pharmacokinetics included anemia, anorexia, constipation, dizziness, elevated liver function test results, fever, headache, heartburn, nausea, vomiting, peripheral and central neurotoxicities, fatigue, and three cases of drug-induced lupus. Disease stabilization for periods of 26+ months, 8 months, and 6 months were seen in hemangioendothelioma, Sertoli-Leydig cell tumor, and fibrosarcoma, respectively. There was a potentially statistically significant relationship between changes in plasma MMP-2 levels and cumulative doses of drug when progressive disease patients were compared with those with stable disease or toxicity (P = .042). CONCLUSION: COL-3 induced disease stabilization in several patients who had a nonepithelial type of malignancy. Phototoxicity was dose-limiting. We recommend the dose of 36 mg/m2/d for phase II trials. PMID- 11208855 TI - Ascertainment of the incidence of Beckwith-Wiedemann syndrome in the National Wilms Tumor Study Group. PMID- 11208856 TI - Blinding of clinical investigators. PMID- 11208857 TI - Hazards of quality-of-life data for clinical decision making. PMID- 11208858 TI - When the tumor is not the target, tell the children. PMID- 11208859 TI - Conflicting phase II efficacy data for Doxil. PMID- 11208860 TI - Bleomycin-induced lung toxicity and pentoxifylline. PMID- 11208861 TI - Complementary therapies in cancer patients. PMID- 11208863 TI - Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. AB - Immunostimulatory properties of dendritic cells (DCs) are linked to their maturation state. Injection of mature DCs rapidly enhances antigen-specific CD4+ and CD8+ T cell immunity in humans. Here we describe the immune response to a single injection of immature DCs pulsed with influenza matrix peptide (MP) and keyhole limpet hemocyanin (KLH) in two healthy subjects. In contrast to prior findings using mature DCs, injection of immature DCs in both subjects led to the specific inhibition of MP-specific CD8+ T cell effector function in freshly isolated T cells and the appearance of MP-specific interleukin 10-producing cells. When pre- and postimmunization T cells were boosted in culture, there were greater numbers of MP-specific major histocompatibility complex tetramer-binding cells after immunization, but these had reduced interferon production and lacked killer activity. These data demonstrate the feasibility of antigen-specific inhibition of effector T cell function in vivo in humans and urge caution with the use of immature DCs when trying to enhance tumor or microbial immunity. PMID- 11208862 TI - Fatal leukemia in interleukin 15 transgenic mice follows early expansions in natural killer and memory phenotype CD8+ T cells. AB - Inflammation likely has a role in the early genesis of certain malignancies. Interleukin (IL)-15, a proinflammatory cytokine and growth factor, is required for lymphocyte homeostasis. Intriguingly, the expression of IL-15 protein is tightly controlled by multiple posttranscriptional mechanisms. Here, we engineered a transgenic mouse to overexpress IL-15 by eliminating these posttranscriptional checkpoints. IL-15 transgenic mice have early expansions in natural killer (NK) and CD8+ T lymphocytes. Later, these mice develop fatal lymphocytic leukemia with a T-NK phenotype. These data provide novel evidence that leukemia, like certain other cancers, can arise as the result of chronic stimulation by a proinflammatory cytokine. PMID- 11208864 TI - Secreted lymphotoxin-alpha is essential for the control of an intracellular bacterial infection. AB - Although the essential role of tumor necrosis factor (TNF) in the control of intracellular bacterial infection is well established, it is uncertain whether the related cytokines lymphotoxin-alpha (LTalpha3) and lymphotoxin-beta (LTbeta) have independent roles in this process. Using C57Bl/6 mice in which the genes for these cytokines have been disrupted, we have examined the relative contribution of secreted LTalpha3 and membrane-bound LTbeta in the host response to aerosol Mycobacterium tuberculosis infection. To overcome the lack of peripheral lymph nodes in LTalpha-/- and LTbeta-/- mice, bone marrow chimeric mice were constructed. LT-/- chimeras, which lack both secreted LTalpha3 and membrane-bound LTbeta (LT1beta2 and LT2beta1), were highly susceptible and succumbed 5 wk after infection. LTbeta-/- chimeras, which lack only the membrane-bound LTbeta, controlled the infection in a comparable manner to wild-type (WT) chimeric mice. T cell responses to mycobacterial antigens and macrophage responses in LTalpha-/- chimeras were equivalent to those of WT chimeras, but in LTalpha-/- chimeras, granuloma formation was abnormal. LTalpha-/- chimeras recruited normal numbers of T cells into their lungs, but the lymphocytes were restricted to perivascular and peribronchial areas and were not colocated with macrophages in granulomas. Therefore, LTalpha3is essential for the control of pulmonary tuberculosis, and its critical role lies not in the activation of T cells and macrophages per se but in the local organization of the granulomatous response. PMID- 11208865 TI - Caspase activation is required for terminal erythroid differentiation. AB - The cysteine proteases known as caspases play a central role in most apoptotic pathways. Here, we show that caspase inhibitors arrest the maturation of human erythroid progenitors at early stages of differentiation, before nucleus and chromatin condensation. Effector caspases such as caspase-3 are transiently activated through the mitochondrial pathway during erythroblast differentiation and cleave proteins involved in nucleus integrity (lamin B) and chromatin condensation (acinus)without inducing cell death and cleavage of GATA-1. These observations indicate a new function for caspases as key proteases in the process of erythroid differentiation. PMID- 11208866 TI - Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2. AB - Prostaglandin (PG)D2, which has long been implicated in allergic diseases, is currently considered to elicit its biological actions through the DP receptor (DP). Involvement of DP in the formation of allergic asthma was recently demonstrated with DP-deficient mice. However, proinflammatory functions of PGD2 cannot be explained by DP alone. We show here that a seven-transmembrane receptor, CRTH2, which is preferentially expressed in T helper type 2 (Th2) cells, eosinophils, and basophils in humans, serves as the novel receptor for PGD2. In response to PGD2, CRTH2 induces intracellular Ca2+mobilization and chemotaxis in Th2 cells in a Galphai-dependent manner. In addition, CRTH2, but not DP, mediates PGD2-dependent cell migration of blood eosinophils and basophils. Thus, PGD2 is likely involved in multiple aspects of allergic inflammation through its dual receptor systems, DP and CRTH2. PMID- 11208867 TI - Signal transducer and activator of transcription (STAT)-induced STAT inhibitor 1 (SSI-1)/suppressor of cytokine signaling 1 (SOCS1) inhibits insulin signal transduction pathway through modulating insulin receptor substrate 1 (IRS-1) phosphorylation. AB - Signal transducer and activator of transcription (STAT)-induced STAT inhibitor 1 (SSI-1) is known to function as a negative feedback regulator of cytokine signaling, but it is unclear whether it is involved in other biological events. Here, we show that SSI-1 participates and plays an important role in the insulin signal transduction pathway. SSI-1-deficient mice showed a significantly low level of blood sugar. While the forced expression of SSI-1 reduced the phosphorylation level of insulin receptor substrate 1 (IRS-1), SSI-1 deficiency resulted in sustained phosphorylation of IRS-1 in response to insulin.Furthermore, SSI-1 achieves this inhibition both by binding directly to IRS-1 and by suppressing Janus kinases. These findings suggest that SSI-1 acts as a negative feedback factor also in the insulin signal transduction pathway through the suppression of IRS-1 phosphorylation. PMID- 11208868 TI - Misregulated posttranscriptional checkpoints: inflammation and tumorigenesis. PMID- 11208869 TI - Differentiation of T regulatory cells by immature dendritic cells. PMID- 11208870 TI - Adjuvant therapy for all patients with breast cancer? PMID- 11208871 TI - Individual variation in p53 responsiveness. PMID- 11208872 TI - Public health burden of cancer in ataxia-telangiectasia heterozygotes. PMID- 11208873 TI - New chapter opens in Iranian research story. PMID- 11208874 TI - LIM kinase appears critical in metastasis, but how? PMID- 11208875 TI - Canada-U.S. mortality comparison highlights analytical pitfalls. PMID- 11208876 TI - International data comparisons: caveat emptor. PMID- 11208877 TI - When theories collide: experts develop different models for carcinogenesis. PMID- 11208878 TI - Stat bite: Smoking habits of young U.S. smokers counseled about tobacco use. PMID- 11208879 TI - Arm edema in breast cancer patients. AB - The improvement in the life expectancy of women with breast cancer raises important questions about how to improve the quality of life for women sustaining complications of breast cancer treatment. In particular, attention to common problems, such as arm edema, is of critical importance. We reviewed published breast cancer guidelines and literature identified via MEDLINE(R) searches in an effort to summarize the research literature pertinent to management of breast cancer-related arm edema, including incidence, prevalence, and timing; risk factors; morbidity; prevention; diagnosis; and efficacy of nonpharmacologic and pharmacologic interventions. We found that arm edema is a common complication of breast cancer therapy that can result in substantial functional impairment and psychological morbidity. The risk of arm edema increases when axillary dissection and axillary radiation therapy are used. Recommendations for preventive measures, such as avoidance of trauma, are available, but these measures have not been well studied. Nonpharmacologic treatments, such as massage and exercise, have been shown to be effective therapies for lymphedema, but the effect of pharmacologic interventions remains uncertain. Comparing results across studies is complicated by the fact that the definitions of interventions and measures of outcomes and risk stratification vary substantially among studies. As arm edema becomes more prevalent with the increasing survival of breast cancer patients, further research is needed to evaluate the efficacy of preventive strategies and therapeutic interventions. PMID- 11208880 TI - Prognosis and treatment of patients with breast tumors of one centimeter or less and negative axillary lymph nodes. AB - BACKGROUND: Uncertainty about prognosis and treatment of axillary lymph node negative patients with estrogen receptor (ER)-negative or ER-positive invasive breast tumors of 1 cm or less prompted the analysis of data from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. METHODS: Two hundred thirty-five patients with ER-negative tumors and 1024 patients with ER-positive tumors were identified in these trials. Patients with ER-negative tumors received surgery alone or surgery and chemotherapy. Patients with ER positive tumors received surgery alone; surgery and tamoxifen; or surgery, tamoxifen, and chemotherapy. End points were relapse-free survival (RFS), event free survival, and overall survival. A result was considered to be statistically significant with a P value of.05 or less; all statistical tests were two-sided. RESULTS: The 8-year RFS of women with ER-negative tumors who received surgery alone or with chemotherapy was 81% and 90%, respectively (P = .06). Survival was similar in both groups (93% and 91%; P = .65). The 8-year RFS of women with ER positive tumors was 86% after surgery alone, 93% when tamoxifen was added (P = .01), and 95% after the addition of tamoxifen and chemotherapy (P = .07 compared with tamoxifen). Survival in the three groups was 90%, 92% (P = .41), and 97%, respectively. The difference between the latter two groups was significant (P = .01). Regardless of ER status or treatment, overall mortality was 8%; one half of the deaths were related to breast cancer. Several covariates affected the risk of recurrence in ER-negative and ER-positive patients. Risk was greater in women with tumors of 1 cm than in those with tumors of less than 1 cm, in women aged 49 years or younger than in those aged 50 years or older, and in women with infiltrating ductal or lobular carcinoma than in those with other histologic tumor types. CONCLUSIONS: Chemotherapy and/or tamoxifen should be considered for the treatment of women with ER-negative or ER-positive tumors of 1 cm or less and negative axillary lymph nodes. PMID- 11208881 TI - Cancer in patients with ataxia-telangiectasia and in their relatives in the nordic countries. AB - BACKGROUND: Epidemiologic studies of the families of patients with ataxia telangiectasia (A-T), a recessive genetic neurologic disorder caused by mutation of the ATM gene, suggest that heterozygous carriers of an ATM mutation are at increased risk of cancer. A population-based study of cancer incidence in A-T families with unbiased selection and tracing of relatives would confirm this hypothesis. METHODS: We conducted a study in the Nordic countries of 1218 blood relatives of 56 A-T patients from 50 families. The relatives were identified from population registries, and the occurrence of cancer was determined from cancer registry files in each country and compared with national incidence rates. All statistical tests were two-sided. RESULTS: Among the 56 patients with A-T, we observed six cases of cancer (four leukemias and two non-Hodgkin's lymphomas) compared with 0.16 expected, yielding a standardized incidence ratio (SIR) of 37 (95% confidence interval [CI] = 13 to 80). Among the 1218 relatives, 150 cancers were recorded, with 126 expected (SIR = 1.19; 95% CI = 1.01 to 1.40). Invasive breast cancer occurred in 21 female relatives of A-T patients (SIR = 1.54; 95% CI = 0.95 to 2.36), including five of the 50 mothers (all of whom are obligate ATM mutation carriers) (SIR = 7.1; 95% CI = 2.3 to 17). Relatives who were less likely to be carriers of a mutant ATM allele had no increase or only a modest, statistically nonsignificant increase in the risk of breast cancer. There was no evidence of increased risk for cancer at any other site. CONCLUSIONS: We confirmed the previously recognized high risk of lymphoma and leukemia in A-T patients. Our data are also consistent with an increased risk of breast cancer among blood relatives of A-T patients. The epidemiologic findings suggest, however, that, even if ATM mutations are responsible for some breast cancer cases, ATM is a relatively weak genetic risk factor for the disease. PMID- 11208882 TI - Induction of p53 expression in skin by radiotherapy and UV radiation: a randomized study. AB - BACKGROUND: p53 protein plays an important role in the response to DNA damage, and radiotherapy can cause radiation dermatitis. p53 and p21 levels increase in vitro when DNA is damaged by UVA, UVB, or gamma-radiation. To determine whether this response occurs in human skin and predicts the level of radiation dermatitis, we investigated levels of p53 and p21 in skin exposed to different types of radiation as part of a randomized study of women with breast cancer to evaluate topical steroid or emollient cream treatments for radiation dermatitis of their irradiated breast. METHODS: After surgery but before receiving tangential 5-mV photo-beam radiotherapy (2 Gy and 54 Gy) to the affected breast parenchyma, multiple areas on the backs of 50 women were irradiated with UVA and other areas were irradiated with UVB. Skin biopsy samples were taken from areas of normal unirradiated skin and all irradiated areas, and p53 and p21 were detected immunohistochemically. All statistical tests are two-sided. RESULTS: In skin irradiated with UVA or UVB, medians of 4.4% (range = 0%-40.5%) or 45.5% (range = 5.3%-74.6%) p53-positive keratinocytes, respectively, were observed. Radiotherapy produced medians of 31.0% (range = 0%-79.3%) p53-immunoreactive cells after 2 Gy of radiation and 83.2% (range = 37.6%-95.2%) after 54 Gy of radiation. Despite large interindividual differences in p53 response, comparable increases in epidermal p53 response were independent of the type of radiation. A correlation between p53 and p21 was also evident (r(s) =.78). In breast skin, there was no association between the p53 response and the degree of erythema (a measure of radiation dermatitis) and no statistically significant difference between treatment arms and p21/p53 responses. CONCLUSIONS: Individual responses to radiation-induced DNA damage varied widely and may be independent of the type of radiation. The epidermal p53 response does not predict the degree of radiation dermatitis. PMID- 11208883 TI - Nicotine yield from machine-smoked cigarettes and nicotine intakes in smokers: evidence from a representative population survey. AB - BACKGROUND: The relevance of nicotine yields from machine-smoked cigarettes for quantifying smokers' nicotine intakes and exposure to cigarette toxins has been called into question. However, most studies of the relationship between nicotine yield and nicotine intake have been on relatively small and unrepresentative samples and have included few smokers of "ultra-low" brands (i.e., those yielding around 1 mg of tar and 0.1 mg of nicotine). METHODS: We examined the relationship between salivary cotinine (a major metabolite of nicotine) concentrations and nicotine yields of machine-smoked cigarettes in a nationally representative sample of 2031 adult smokers of manufactured cigarettes surveyed in the 1998 Health Survey for England. We used standard linear regression techniques to examine associations and two-sided tests of statistical significance. RESULTS: Cotinine concentrations varied widely between smokers at any level of nominal brand nicotine yield. On average, cotinine levels were slightly lower in smokers of lower nicotine-yielding brands, but these smokers differed in terms of sex, socioeconomic profile, and cigarette consumption. After we controlled for potential confounders, nicotine yield from the brand smoked accounted for only 0.79% of the variation in saliva cotinine concentrations. Nicotine intake per cigarette smoked, as estimated from salivary cotinine level, did not correspond with machine-smoked yields at any level of nicotine yield. Nicotine intake per cigarette was about eight times greater than machine-smoked yields at the lowest deliveries (1.17 mg estimated nicotine intake per cigarette from brands averaging 0.14-mg delivery from machine smoking) and 1.4 times greater for the highest yield cigarettes (1.31-mg estimated nicotine intake per cigarette from brands averaging 0.91 mg from machine smoking). CONCLUSIONS: Smokers' tendency to regulate nicotine intake vitiates potential health gains from lower tar and nicotine cigarettes. Current approaches to characterizing tar and nicotine yields of cigarettes provide a simplistic guide to smokers' exposure that is misleading to consumers and regulators alike and should be abandoned. PMID- 11208884 TI - Quality of informed consent: a new measure of understanding among research subjects. AB - BACKGROUND: The informed consent of participants is ethically and legally required for most research involving human subjects. However, standardized methods for assessing the adequacy of informed consent to research are lacking. METHODS AND RESULTS: We designed a brief questionnaire, the Quality of Informed Consent (QuIC), to measure subjects' actual (objective) and perceived (subjective) understanding of cancer clinical trials. The QuIC incorporates the basic elements of informed consent specified in federal regulations, assesses the therapeutic misconception (the belief that all aspects of a clinical trial are designed to directly benefit the subject), and employs the language and structure of the new National Cancer Institute template for informed consent documents. We modified the QuIC after receiving feedback from pilot tests with cancer research subjects, as well as validation from two independent expert panels. We then sent the QuIC to 287 adult cancer patients enrolled on phase I, II, or III clinical trials. Two hundred seven subjects (72%) completed the QuIC. To assess test retest reliability, a random sample of 32 respondents was selected, of whom 17 (53%) completed the questionnaire a second time. The test-retest reliability was good with intraclass correlation coefficients of.66 for tests of objective understanding and.77 for tests of subjective understanding. The current version of the QuIC, which consists of 20 questions for objective understanding and 14 questions for subjective understanding, was tested for time and ease of administration in a sample of nine adult cancer patients. The QuIC required an average of 7.2 minutes to complete. CONCLUSIONS: The QuIC is a brief, reliable, and valid questionnaire that holds promise as a standardized way to assess the outcome of the informed consent process in cancer clinical trials. PMID- 11208885 TI - Epstein-Barr virus detection in ductal carcinoma of the breast. PMID- 11208887 TI - Re: Biologic characteristics of interval and screen-detected breast cancers. PMID- 11208888 TI - Re: Population-based study of BRCA1 and BRCA2 mutations in 1035 unselected Finnish breast cancer patients. PMID- 11208891 TI - Intrafamilial transmission of human herpesvirus 8. PMID- 11208894 TI - Re: Randomized trial of a specialist genetic assessment service for familial breast cancer. PMID- 11208892 TI - Re: Population stratification in epidemiologic studies of common genetic variants and cancer: quantification of bias. PMID- 11208895 TI - Cyclic ADP-ribose as a potential second messenger for neuronal Ca2+ signaling. AB - Cyclic ADP-ribose (cADPR), a known endogenous modulator of ryanodine receptor Ca2+ releasing channels, is found in the nervous system. Injection of cADPR into neuronal cells primarily induces a transient elevation of intracellular Ca2+ concentration ([Ca2+]i), and/or secondarily potentiates [Ca2+]i increases that are the result of depolarization-induced Ca2+ influx. Acetylcholine release from cholinergic neurons is facilitated by cADPR. cADPR modifies K+ currents or elicits Ca2+-dependent inward currents. cADPR is synthesized by both membrane bound and cytosolic forms of ADP-ribosyl cyclase in neuronal cells. cADPR hydrolase activity is weak in the membrane fraction, but high in the cytoplasm. Cytosolic ADP-ribosyl cyclase activity is upregulated by nitric oxide/cyclic GMP dependent phosphorylation. Stimulation of muscarinic and beta-adrenergic receptors activates membrane-bound ADP-ribosyl cyclase via G proteins within membranes of neuronal tumor cells and cortical astrocytes. These findings strongly suggest that cADPR is a second messenger in Ca2+ signaling in the nervous system, although many intriguing issues remain to be addressed before this identity is confirmed. PMID- 11208896 TI - Expression and localization of the CYP2B subfamily predominantly in neurones of rat brain. AB - Despite the very small amounts of cytochrome P450 (P450, CYP) enzymes expressed in different areas and cell populations of the brain as compared with the liver, there is significant evidence for their specific involvement in brain development, function and plasticity. Nevertheless, the current discussion about occurrence and importance of cerebral cytochrome P450s is determined by inconsistent interpretations of their function in general and with respect to single isoforms. Continuing a series of publications about brain P450 isoforms, we now present evidence for the constitutive expression of CYP2B1 and CYP2B2 mRNAs in rat brain. Immunocytochemical and non-radioactive in situ hybridization studies revealed the same expression pattern throughout the brain predominantly in neuronal populations, but to some extent in astrocytes of corpus callosum and olfactory bulb. The well known testosterone-metabolizing capacity and the presence of CYP2B isoforms shown in steroid hormone-sensitive areas and neurones (e.g. hippocampus) clarify the significance of isoforms like CYP2B1 and CYP2B2 for impairment of steroid hormone actions by P450 inducing environmental substances. We argue that cerebral P450 isoforms which are induced by xenobiotics and are able to metabolize these as well as endogenous substrates help us to understand fundamental aspects of brain's functioning. PMID- 11208897 TI - Peroxynitrite affects Ca2+ influx through voltage-dependent calcium channels. AB - The effect of peroxynitrite (OONO-) on voltage-dependent Ca2+ channels (VDCCs) was examined by measuring [45Ca2+] influx into mouse cerebral cortical neurones. OONO- time- and dose-dependently increased [45Ca2+] influx and this increase was abolished by manganese (III) tetrakis (4-benzoic acid) porphyrin, a scavenger for OONO-. Inhibition of cyclic GMP (cGMP) formation did not alter the OONO(-) induced [45Ca2+] influx. OONO-, as well as 30 mm KCl, significantly increased fluorescence intensity of cell-associated bis-(1,3-dibutylbarbituric acid) trimethine oxonol (bis-oxonol). Tetrodotoxin and membrane stabilizers such as lidocaine dose-dependently suppressed OONO(-)-induced [45Ca2+] influx. Although each of 1 microM nifedipine and 1 microM omega-agatoxin VIA (omega-ATX) significantly inhibited the OONO(-)-induced [45Ca2+] influx and the concomitant presence of these agents completely abolished the influx, 1 microM omega conotoxin GVIA (omega-CTX) showed no effect on the influx. On the other hand, OONO- itself reduced 30 mM KCl-induced [45Ca2+] influx to the level of [45Ca2+] influx induced by OONO- alone, and the magnitude of this reduction was as same as that of KCl-induced [45Ca2+] influx by omega-CTX. These results indicate that OONO- increases [45Ca2+] influx into the neurones through opening P/Q- and L-type VDCCs subsequent to depolarization, and inhibits the influx through N-type VDCCs. PMID- 11208898 TI - Group II metabotropic glutamate receptor activation protects striatal dopaminergic nerve terminals against MPP+-induced neurotoxicity along with brain derived neurotrophic factor induction. AB - We have studied the in vivo effect of the selective agonist for group II metabotropic glutamate receptors (2S, 2'R, 3'R)-2-(2'3' dicarboxycyclopropyl)glycine (DCG-IV) against MPP+-induced toxicity on rat striatal dopaminergic nerve terminals by using both microdialysis and immunohistochemical techniques. Perfusion of 1 mM DCG-IV during 1 h protected dopaminergic nerve terminals against the degeneration induced by a 15-minute perfusion of 1 mM MPP+. In addition, the microglial cell population was markedly activated 24 h after DCG-IV perfusion. The astroglial cell population was only markedly activated around the microdialysis probe. This protective effect seems to be dependent on protein synthesis since 1 mM cycloheximide, an inhibitor of protein synthesis, abolished the neuroprotective effect of 1 mM DCG-IV against MPP+ toxicity. Perfusion of DCG-IV induced an upregulation of striatal brain derived neurotrophic factor (BDNF) mRNA expressing cells which were confined precisely around the microdialysis probe. Taken together, our results suggest that the induction and release of brain-derived neurotrophic factor (BDNF) by activated glial cells induced by DCG-IV perfusion may account for its protective action against MPP+-induced dopaminergic terminal degeneration. PMID- 11208899 TI - Protein kinase C activation by 12-0-tetradecanoylphorbol 13-acetate in CG-4 line oligodendrocytes stimulates turnover of choline and ethanolamine phospholipids by phospholipase D and induces rapid process contraction. AB - Treatment of [3H]-choline- or [14C]-ethanolamine-labelled undifferentiated bipolar and differentiated multipolar CG-4 line oligodendrocytes with 12-0 tetradecanoylphorbol 13-acetate (TPA) to activate protein kinase C stimulated the release of choline or ethanolamine metabolites to the medium over controls. Ro31 8220, a PKC inhibitor, reduced TPA-stimulated release of choline- and ethanolamine-metabolites to basal levels. TPA treatment of both bipolar and multipolar cells caused rapid contraction of processes leaving rounded up cells: this effect was blocked by Ro31-8220. After 12-15 h exposure to TPA, bipolar undifferentiated CG-4 line cells extended short processes again and the cells became multipolar. Nocodozole, an agent which disrupts microtubules and caused CG 4 line cells to round up, caused increased choline or ethanolamine-metabolite release to the medium over basal levels suggesting that some release during TPA treatment might occur due to process fragmentation. However, the transphosphatidylation reaction confirmed that phospholipase D was active in these cells. Exposure of bipolar undifferentiated CG-4 line cells to TPA resulted in down-regulatation of PKC-alpha and PKC-beta which could not be detected by Western blotting after a few hours; PKC-epsilon was down-regulated much more slowly but PKCs delta, zeta and iota were not influenced by 48 h exposure of cells to TPA. Formation of phosphatidylethanol in the transphosphatidylation reaction was markedly reduced in TPA down-regulated cells indicating a role for PKCs alpha and beta in phospholipase D activation in CG-4 line oligodendrocytes. PMID- 11208900 TI - Parallel modification of adenosine extracellular metabolism and modulatory action in the hippocampus of aged rats. AB - The neuromodulator adenosine can be released as such, mainly activating inhibitory A1 receptors, or formed from released ATP, preferentially activating facilitatory A2A receptors. We tested if changes in extracellular adenosine metabolism paralleled changes in A1/A2A receptor neuromodulation in the aged rat hippocampus. The evoked release and extracellular catabolism of ATP were 49-55% lower in aged rats, but ecto-5'-nucleotidase activity, which forms adenosine, was 5-fold higher whereas adenosine uptake was decreased by 50% in aged rats. The evoked extracellular adenosine accumulation was 30% greater in aged rats and there was a greater contribution of the ecto-nucleotidase pathway and a lower contribution of adenosine transporters for extracellular adenosine formation in nerve terminals. Interestingly, a supramaximal concentration of an A1 receptor agonist, N6-cyclopentyladenosine (250 nM) was less efficient in inhibiting (17% in old versus 34% in young) and A2A receptor activation with 30 nM CGS21680 was more efficient in facilitating (63% in old versus no effect in young) acetylcholine release from hippocampal slices of aged compared with young rats. The parallel changes in the metabolic sources of extracellular adenosine and A1/A2A receptor neuromodulation in aged rats further strengthens the idea that different metabolic sources of extracellular adenosine are designed to preferentially activate different adenosine receptor subtypes. PMID- 11208901 TI - Survival activity of troglitazone in rat motoneurones. AB - Troglitazone (TGZ), an antidiabetic drug that improves insulin-resistance in the peripheral tissues, was tested for neurotrophic activity in motoneurones and other neurones in culture. In rat motoneurones, TGZ had a remarkable effect on survival, which was comparable or superior to that of brain-derived neurotrophic factor, a known potent neurotrophic factor for rat motoneurones. However, TGZ did not promote the survival of sensory, sympathetic, septal or hippocampal neurones. The effect of TGZ on motoneurones was additive to that of insulin-like growth factor-I and both activities were inhibited by phosphatidylinositol 3-kinase (PI3 kinase) inhibitors, wortmannin and LY294002, suggesting the involvement of the activation of PI3-kinase in the activity of TGZ. Pioglitazone, another antidiabetic drug structurally similar to TGZ, did not show any activity, indicating that the agonistic activity of TGZ for peroxisome proliferator activated receptor-gamma is not involved in the survival activity. Chromanol, an antioxidant moiety of TGZ, showed little or no survival activity. These results indicate specific neurotrophic activity of TGZ for motoneurones through the activation of PI3-kinase and support the applicability of TGZ for the treatment of motor neurone diseases such as amyotrophic lateral sclerosis. PMID- 11208902 TI - Cholesterol-dependent modulation of tau phosphorylation in cultured neurons. AB - One of the hallmarks of Alzheimer's disease (AD) is the abnormal state of tau. It is both highly phosphorylated and aggregated into paired helical filaments (PHFs) in neurofibrillary tangles (NFTs). However, the mechanism underlying the hyperphosphorylation of tau in NFTs and neuronal degeneration in AD remains to be elucidated. The fact that hyperphosphorylation of tau in NFTs are also found in the patients with Niemann-Pick disease, type C (NPC), which is a cholesterol storage disease associated with defective intracellular trafficking of exogenous cholesterol, implies that perturbation of cholesterol metabolism may be involved in tau phosphorylation and neurodegeneration. Here, we report that cholesterol deficiency induced by inhibition of cholesterol biosynthesis in cultured neurons results in hyperphosphorylation of tau, accompanied by axonal degeneration associated with microtubule depolymerization. These changes were prevented by concurrent treatment with beta-migrating very low-density lipoprotein (beta-VLDL) or cholesterol. We propose that intracellular cholesterol plays an essential role in the modulation of tau phosphorylation and the maintenance of microtubule stability. PMID- 11208903 TI - Cyclic AMP and mitogen-activated protein kinases are required for glutamate dependent cyclic AMP response element binding protein and Elk-1 phosphorylation in the dorsal striatum in vivo. AB - Dopaminergic and glutamatergic signalling cascades are integrated in striatal medium spiny neurones by cyclic AMP response-element binding protein and Elk-1 phosphorylation. Phosphorylated cyclic AMP response-element binding protein and phosphorylated Elk-1 contribute to c-fos expression by binding to the calcium and cyclic AMP response-element and the serum response element, respectively, in the c-fos promoter. The role of cyclic AMP and mitogen-activated protein kinase signalling cascades in glutamate-induced cyclic AMP response-element binding protein and Elk-1 phosphorylation and Fos expression was investigated using semiquantitative immunocytochemistry in vivo. Intracerebroventricular infusion of the sodium channel blocker, tetrodotoxin, decreased the glutamate-induced increase in phosphorylated cyclic AMP response-element binding protein, phosphorylated Elk-1, and Fos immunoreactivity. Intracerebroventricular infusion of the mitogen-activated and extracellular signal-regulated kinase inhibitor, PD98059, the p38 mitogen-activated protein kinase inhibitor, SB203580, or the cyclic AMP inhibitor, Rp-8-Br-cAMPS, decreased glutamate-induced phosphorylated cyclic AMP response-element binding protein, phosphorylated Elk-1, and Fos immunoreactivity. Simultaneous infusion of glutamate and Sp-8-Br-cAMPS, a cyclic AMP analogue, augmented induction of Fos immunoreactivity but not phosphorylated cyclic AMP response-element binding protein or phosphorylated Elk-1 immunoreactivity. These data indicate that cyclic AMP and mitogen-activated protein kinase signalling cascades are necessary for glutamate to induce cyclic AMP response-element binding protein and Elk-1 phosphorylation and Fos expression in the striatum. Furthermore, neuronal activity plays an important role in glutamate-induced signalling cascades in vivo. PMID- 11208904 TI - Carbohydrate-protein interactions between HNK-1-reactive sulfoglucuronyl glycolipids and the proteoglycan lectin domain mediate neuronal cell adhesion and neurite outgrowth. AB - Lecticans, a family of chondroitin sulfate proteoglycans, represent the largest group of proteoglycans expressed in the nervous system. We previously showed that the C-type lectin domains of lecticans bind two classes of sulfated cell surface glycolipids, sulfatides and HNK-1-reactive sulfoglucuronylglycolipids (SGGLs). In this paper, we demonstrate that the interaction between the lectin domain of brevican, a nervous system-specific lectican, and cell surface SGGLs acts as a novel cell recognition system that promotes neuronal adhesion and neurite outgrowth. The Ig chimera of the brevican lectin domain bind to the surface of SGGL-expressing rat hippocampal neurons. The substrate of the brevican chimera promotes adhesion and neurite outgrowth of hippocampal neurons. The authentic, full-length brevican also promotes neuronal cell adhesion and neurite outgrowth. These activities of brevican substrates are neutralized by preincubation of cells with HNK-1 monoclonal antibodies and by pretreatment of the brevican substrates with purified SGGLs. Brevican and HNK-1 carbohydrates are coexpressed in specific layers of the developing hippocampus where axons from entorhinal neurons elongate. Our observations suggest that cell surface SGGLs and extracellular lecticans comprise a novel cell-substrate recognition system operating in the developing nervous system. PMID- 11208905 TI - On the mechanisms of neuroprotection by creatine and phosphocreatine. AB - Creatine and phosphocreatine were evaluated for their ability to prevent death of cultured striatal and hippocampal neurons exposed to either glutamate or 3 nitropropionic acid (3NP) and to inhibit the mitochondrial permeability transition in CNS mitochondria. Phosphocreatine (PCr), and to a lesser extent creatine (Cr), but not (5R,10S)-(+)-5-methyl-10,11-dihydro-5H dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK801), dose-dependently ameliorated 3NP toxicity when applied simultaneously with the 3NP in Mg2+-free media. Pre-treatment of PCr for 2 or 5 days and Cr for 5 days protected against glutamate excitotoxicity equivalent to that achieved by MK801 post-treatment. The combination of PCr or Cr pre-treatment and MK801 post-treatment did not provide additional protection, indicating that both prevented the toxicity attributable to secondary glutamate release. To determine if Cr or PCr directly inhibited the permeability transition, mitochondrial swelling and depolarization were assayed in isolated, purified brain mitochondria. PCr reduced the amount of swelling induced by calcium by 20%. Cr decreased mitochondrial swelling when inhibitors of creatine kinase octamer-dimer transition were present. However, in brain mitochondria prepared from rats fed a diet supplemented with 2% creatine for 2 weeks, the extent of calcium-induced mitochondrial swelling was not altered. Thus, the neuroprotective properties of PCr and Cr may reflect enhancement of cytoplasmic high-energy phosphates but not permeability transition inhibition. PMID- 11208906 TI - Activation and redistribution of c-jun N-terminal kinase/stress activated protein kinase in degenerating neurons in Alzheimer's disease. AB - Cellular responses to increased oxidative stress appear to be a mechanism that contributes to the varied cytopathology of Alzheimer's disease (AD). In this regard, we suspect that c-Jun N-terminal kinase/Stress activated protein kinase (JNK/SAPK), a major cellular stress response protein induced by oxidative stress, plays an important role in Alzheimer disease in susceptible neurons facing the dilemma of proliferation or death. We found that JNK2/SAPK-alpha and JNK3/SAPK beta were related to neurofibrillary pathology and JNK1/SAP-Kgamma related to Hirano bodies in cases of AD but were only weakly diffuse in the cytoplasm in all neurons in control cases and in non-involved neurons in diseased brain. In this regard, in hippocampal and cortical regions of individuals with severe AD, the activated phospho-JNK/SAPK was localized exclusively in association with neurofibrillar alterations including neurofibrillary tangles, senile plaque neurites, neuropil threads and granulovacuolar degeneration structures (GVD), completely overlapping with tau-positive neurofibrillary pathology, but was virtually absent in these brain regions in younger and age-matched controls without pathology. However, in control patients with some pathology, as well as in mild AD cases, there was nuclear phospho-JNK/SAPK and translocation of phospho JNK/SAPK from nuclei to cytoplasm, respectively, indicating that the activation and re-distribution of JNK/SAPK correlates with the progress of the disease. By immunoblot analysis, phospho-JNK/SAPK is significantly increased in AD over control cases. Together, these findings suggest that JNK/SAPK dysregulation, probably resulting from oxidative stress, plays an important role in the increased phosphorylation of cytoskeletal proteins found in AD. PMID- 11208907 TI - Reduction of glyceraldehyde-3-phosphate dehydrogenase activity in Alzheimer's disease and in Huntington's disease fibroblasts. AB - New functions have been identified for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) including its role in neurodegenerative disease and in apoptosis. GAPDH binds specifically to proteins implicated in the pathogenesis of a variety of neurodegenerative disorders including the beta-amyloid precursor protein and the huntingtin protein. However, the pathophysiological significance of such interactions is unknown. In accordance with published data, our initial results indicated there was no measurable difference in GAPDH glycolytic activity in crude whole-cell sonicates of Alzheimer's and Huntington's disease fibroblasts. However, subcellular-specific GAPDH-protein interactions resulting in diminution of GAPDH glycolytic activity may be disrupted or masked in whole-cell preparations. For that reason, we examined GAPDH glycolytic activity as well as GAPDH-protein distribution as a function of its subcellular localization in 12 separate cell strains. We now report evidence of an impairment of GAPDH glycolytic function in Alzheimer's and Huntington's disease subcellular fractions despite unchanged gene expression. In the postnuclear fraction, GAPDH was 27% less glycolytically active in Alzheimer's cells as compared with age-matched controls. In the nuclear fraction, deficits of 27% and 33% in GAPDH function were observed in Alzheimer's and Huntington's disease, respectively. This evidence supports a functional role for GAPDH in neurodegenerative diseases. The possibility is considered that GAPDH:neuronal protein interaction may affect its functional diversity including energy production and as well as its role in apoptosis. PMID- 11208908 TI - ortho-substituted PCB95 alters intracellular calcium signaling and causes cellular acidification in PC12 cells by an immunophilin-dependent mechanism. AB - ortho-Substituted PCBs mobilize Ca2+ from isolated brain microsomes by interaction with FKBP12/RyR complexes. Investigation into the cellular importance of this mechanism was undertaken using PC12 cells by fluoroimaging the actions of specific PCB congeners on [Ca2+]i and pH. RyR and IP3R share a common intracellular Ca2+ store in PC12 cells. Perfusion of nM to low microM PCB95 caused a transient rise of [Ca2+]i that was not completely dependent on extracellular Ca2+. Pre-incubation of the cells with ryanodine or FK506 completely eliminated PCB95 responses, suggesting a primary action on the FKPP12/RyR-sensitive store. PCB95, but not PCB126, induced a gradual decrease in cytosolic pH that could be completely eliminated by FK506 pre-incubation of the cells. Direct respiration measurement using isolated brain mitochondria demonstrated that neither of the PCBs directly altered any stage of mitochondrial respiration. These results revealed that PCB95 disrupts intracellular Ca2+ signaling in PC12 cells by interaction with the FKBP12/RyR complex that in turn accelerated cellular metabolism, possibly affecting signaling between ER and mitochondria. Since ortho-substituted PCBs have been shown to be neurotoxic and may affect neurodevelopment, studies on the molecular mechanism by which they alter cellular signaling may provide valuable information on the physiological roles of FKPB12 and RyR on neuronal functions. PMID- 11208910 TI - Acute ethanol exposure induces [Ca2+]i transients, cell swelling and transformation of actin cytoskeleton in astroglial primary cultures. AB - Acute exposure to 100 mM isotonic ethanol (EtOH) increased intracellular Ca2+ concentration ([Ca2+]i), induced cell swelling, and transformed actin cytoskeleton in astroglial primary cultures from rat cerebral cortex. Fluorometric recordings of fluo-3AM- or fura-2AM-incubated astroglial cells revealed that EtOH induced [Ca2+]i transients in a small population of the cells. Cell swelling was estimated using a new method based on three-dimensional fluorescence imaging in conjunction with image analysis and graphic visualization techniques. The method provides detailed results concerning the reformation of structural shape and specific volume alterations, as well as total proportions between the different states. Astroglial cell swelling was registered and quantified in 7 of 39 cells chosen from 12 different coverslips. EtOH also induced reversible conformational changes in filamentous actin, appearing as increases in ring formations and a more dispersed appearance of the filaments. Filamentous actin was stained with Alexa phalloidin after incubation with EtOH for varied periods. The results presented here suggest that EtOH affects astrocytes in a way that could be of physiological relevance. PMID- 11208909 TI - Morphological and neurochemical identification of enteric neurones with mucosal projections in the human small intestine. AB - Data on the axonal projections of enteric neurones in the human intestine are still scarce. The present study aimed to identify the morphology and neurochemical coding of enteric neurones in the human small intestine, which are involved in the innervation of the mucosa. The lipophilic neuronal tracer DiI was applied to one mucosal villus of small intestinal resection specimens. The tissue was kept in organotypic culture and subsequently processed for immunohistochemistry. Neurones labelled from the mucosa were located in all ganglionated nerve networks, including the myenteric plexus. In all plexuses, at least five neurochemical types of neurones could be observed, i.e. SOM-IR neurones, SP-IR neurones, SOM/SP-IR neurones, VIP-IR neurones and neurones lacking immunoreactivity for any of these markers. Most of the DiI-labelled neurones were multidendritic; a minority of neurones could be identified as Dogiel type II cells, suggesting the existence of a subgroup of primary afferent neurones in the DiI-filled cell population. The ratio of labelled multidendritic neurones (assumed to be secretomotor) to labelled Dogiel type II neurones (assumed to be primary afferent) in the myenteric plexus is higher in large mammals (pig and human) than in small mammals (guinea pig). This might point to the existence of a different topographical distribution of subsets of primary afferent neurones and/or topographically distinct intrinsic mucosal reflex circuits in large mammals, including humans. PMID- 11208911 TI - Piroxicam and NS-398 rescue neurones from hypoxia/reoxygenation damage by a mechanism independent of cyclo-oxygenase inhibition. AB - We studied whether NS-398, a selective cyclo-oxygenase-2 (COX-2) enzyme inhibitor, and piroxicam, an inhibitor of COX-2 and the constitutively expressed COX-1, protect neurones against hypoxia/reoxygenation injury. Rat spinal cord cultures were exposed to hypoxia for 20 h followed by reoxygenation. Hypoxia/reoxygenation increased lactate dehydrogenase (LDH) release, which was inhibited by piroxicam (180-270 microM) and NS-398 (30 microM). Cell counts confirmed the neuroprotection. Western blotting revealed no COX-1 or COX-2 proteins even after hypoxia/reoxygenation. Production of prostaglandin E2 (PGE2), a marker of COX activity, was barely measurable and piroxicam and NS-398 had no effect on the negligible PGE2 production. Hypoxia/reoxygenation increased nuclear factor-kappa B (NF-kappaB) binding activity, which was inhibited by piroxicam but not by NS-398. AP-1 binding activity after hypoxia/reoxygenation was inhibited by piroxicam but strongly enhanced by NS-398. However, both COX inhibitors induced activation of extracellular signal-regulated kinase (ERK) in neurones and phosphorylation of heavy molecular weight neurofilaments, cytoskeletal substrates of ERK. It is concluded that piroxicam and NS-398 protect neurones against hypoxia/reperfusion. The protection is independent of COX activity and not solely explained by modulation of NF-kappaB and AP-1 binding activity. Instead, piroxicam and NS-398-induced phosphorylation through ERK pathway may contribute to the increased neuronal survival. PMID- 11208912 TI - Effect of subchronic lithium treatment on citalopram-induced increases in extracellular concentrations of serotonin in the medial prefrontal cortex. AB - We investigated the effect of citalopram [a selective serotonin (5-HT) reuptake inhibitor; SSRI] and MKC-242 (a selective 5-HT1A agonist), following treatment with subchronic lithium (p.o., 1 week) on extracellular 5-HT concentrations in the medial prefrontal cortex (mPFC). Acute treatment with citalopram (3 and 30 mg/kg) led to significant increases in extracellular 5-HT concentrations. The subchronic lithium group showed significantly higher basal levels of extracellular 5-HT than normal diet controls. Acute citalopram (3 and 30 mg/kg) treatment together with subchronic lithium treatment showed significant increases in the extracellular 5-HT concentrations, compared with citalopram treatment alone. Acute MKC-242 (1 mg/kg) treatment showed significant decreases in extracellular 5-HT concentrations, in both the normal diet and lithium diet groups to the same extent. The addition of lithium did not change the effect of the 5-HT1A agonist on extracellular 5-HT concentrations. This study suggests that lithium augmentation of the antidepressant effect of SSRI is mediated by the additional increases in extracellular 5-HT concentrations following the co administrations of lithium and SSRI. PMID- 11208913 TI - Scavenger receptor class B, type I is expressed in porcine brain capillary endothelial cells and contributes to selective uptake of HDL-associated vitamin E. AB - It is clearly established that an efficient supply to the brain of alpha tocopherol (alphaTocH), the most biologically active member of the vitamin E family, is of the utmost importance for proper neurological functioning. Although the mechanism of uptake of alphaTocH into cells constituting the blood-brain barrier (BBB) is obscure, we previously demonstrated that high-density lipoprotein (HDL) plays a major role in the supply of alphaTocH to porcine brain capillary endothelial cells (pBCECs). Here we studied whether a porcine analogue of human and rodent scavenger receptor class B, type I mediates selective (without concomitant lipoprotein particle internalization) uptake of HDL associated alphaTocH in a similar manner to that described for HDL-associated cholesteryl esters (CEs). In agreement with this hypothesis we observed that a major proportion of alphaTocH uptake by pBCECs occurred by selective uptake, exceeding HDL3 holoparticle uptake by up to 13-fold. The observation that selective uptake of HDL-associated CE exceeded HDL3 holoparticle up to fourfold suggested that a porcine analogue of SR-BI (pSR-BI) may be involved in lipid uptake at the BBB. In line with the observation of selective lipid uptake, RT-PCR and northern and western blot analyses revealed the presence of pSR-BI in cells constituting the BBB. Adenovirus-mediated overexpression of the human analogue of SR-BI (hSR-BI) in pBCECs resulted in a fourfold increase in selective HDL associated alphaTocH uptake. In accordance with the proposed function of SR-BI, selective HDL-CE uptake was increased sixfold in Chinese hamster ovary cells stably transfected with murine SR-BI (mSR-BI). Most importantly stable mSR-BI overexpression mediated a twofold increase in HDL-associated [14C]alphaTocH selective uptake in comparison with control cells. In line with tracer experiments, mass transfer studies with unlabelled lipoproteins revealed that mSR BI overexpression resulted in a twofold increase in endogenous HDL3-associated alphaTocH uptake. The results of this study indicate that SR-BI promotes the uptake of HDL-associated alphaTocH into cells constituting the BBB and plays an important role during the supply of the CNS with this indispensable micronutrient. PMID- 11208914 TI - Rat cerebral cortex corticotropin-releasing hormone receptors: evidence for receptor coupling to multiple G-proteins. AB - The wide distribution of corticotrophin-releasing hormone (CRH) receptors in brain and periphery appear to be important in integrating the responses of the brain, endocrine and immune systems to physiological, psychological and immunological stimuli. The type 1 receptors are highly expressed throughout the cerebral cortex, a region involved in cognitive function and modulation of stress responses, where they are coupled to the adenylyl cyclase system. Using techniques that analyse receptor-mediated guanine-nucleotide binding protein (G proteins) activation, we recently demonstrated that expressed type 1alpha CRH receptors are capable of activating multiple G-proteins, which suggests that CRH can regulate multiple signalling pathways. In an effort to characterize the intracellular signals generated by CRH in the rat cerebral cortex we sought to identify G-proteins activated by CRH in a physiological membrane environment. Rat cerebral cortical membrane suspensions were analysed for the ability of CRH to stimulate incorporation of [alpha-32P]-GTP-gamma-azidoanilide to various G protein alpha-chains. Our results show that CRH receptors are coupled to and activate at least five different G-proteins (Gs, Gi, Gq/11, Go and Gz) with subsequent stimulation of at least two intracellular signalling cascades. In addition, the photoaffinity experiments indicated that the CRH receptors preferentially activate the 45 kDa form of the Gs alpha-protein. This data may help elucidate the intracellular signalling pathways mediating the multiple actions of CRH especially under different physiological conditions. PMID- 11208915 TI - Neuronal death is an active, caspase-dependent process after moderate but not severe DNA damage. AB - Mild insults to neurons caused by ischemia or glutamate induce apoptosis, whereas severe insults induce non apoptotic death, such as necrosis. The molecular targets that are damaged by these insults and ultimately induce cell death are not fully established. To determine if DNA damage can induce apoptotic or non apoptotic death depending on the severity, neurons were treated with up to 128 Gy of ionizing radiation. Such treatment induced a dose-related increase in DNA single-strand breaks but no immediate membrane disruption or lipid peroxidation. Following moderate doses of < or = 32 Gy, neuronal death had many characteristics of apoptosis including nuclear fragmentation and DNA laddering. Nuclear fragmentation and membrane breakdown after moderate DNA damage could be blocked by inhibition of active protein synthesis with cycloheximide and by inhibition of caspases. In contrast, cell death after doses of > 32 Gy was not blocked by cycloheximide or caspase inhibitors, and membrane breakdown occurred relatively early in the cell death process. These data suggest that cell death after high dose irradiation and severe DNA damage can occur by non apoptotic mechanisms and that blocking apoptotic pathways may not prevent death after severe damage. PMID- 11208916 TI - Inducible nitric oxide synthase expression in brain cortex after acute restraint stress is regulated by nuclear factor kappaB-mediated mechanisms. AB - The underlying mechanisms by which physical or psychological stress causes neurodegeneration are still unknown. We have demonstrated that the high-output and long-lasting synthesizing source of nitric oxide (NO), inducible NO synthase (iNOS), is expressed in brain cortex during stress and that its overexpression accounts for the neurodegenerative changes seen after 3 weeks of repeated stress. Now we have found that acute stress (restraint for 6 h) increases the activity of a calcium-independent NOS and induces the expression of iNOS in brain cortex in adult male rats. In order to elucidate the possible mechanisms involved in this induction, we studied the role of transcription nuclear factor kappaB (NF kappaB), which is required for iNOS synthesis. We have observed that an acute restraint stress session stimulates the translocation of the NF-kappaB to the nucleus after 4 h and that the administration of the NF-kappaB inhibitor pyrrolidine dithiocarbamate [PDTC, 75 and 150 mg/kg intraperitoneally (i.p.)] at the onset of stress inhibits the stress-induced increase in iNOS expression. Since glutamate release and subsequent NMDA (N-methyl-D-aspartate) receptor activation has been recognized as an early change after exposure to stressful stimuli, and glutamate has been shown to induce iNOS in brain via a NF-kappaB dependent mechanism, we studied the possible role of excitatory amino acids in the induction of iNOS in our model. Pretreatment with the NMDA receptor antagonist dizocilpine (MK-801, 0.1 and 0.3 mg/kg i.p.) inhibits the stress induced NF-kappaB activation as well as the stress-induced increase in iNOS expression. Taken together, these findings indicate that excitatory amino acids and subsequent activation of NF-kappaB account for stress-induced iNOS expression in cerebral cortex, and support a possible neuroprotective role for specific inhibitors in this situation. PMID- 11208917 TI - Site of injury-directed induction of heme oxygenase-1 and -2 in experimental spinal cord injury: differential functions in neuronal defense mechanisms? AB - The heme oxygenase (HO) isozymes catalyze oxidation of the heme molecule to biliverdin and carbon monoxide (CO) with the release of chelated iron. Presently, we have defined, for the first time, propensity for site of injury-directed induction of isozymes--the stress-inducible isozyme, HO-1, responds distal (below) and the glucocorticoid (GC)-inducible HO-2 responds proximal (above) to the site of injury. We have also shown that reactive iron (Fe3+) and cGMP staining spatially resemble that of HO-1; which, in turn, colocalizes in motor neurons with transcription factors: Fas-associated protein containing death domain (FADD), tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and p53. Spinal cord injury (SCI) was inflicted by clip compression for 30 min, and analyses were carried out after 4 h or 16 h. When compared with spinal cord segments proximal to the site of injury, northern blot analysis showed remarkably higher levels of HO-1 mRNA distal (below) to the site of injury at both time points. In contrast, HO-2 mRNA levels were elevated proximal (above) to the site of injury and more prominently at 16 h post SCI. Immunohistochemical analyses were carried out using 2 x 5 mm segments above and below the compression site. When compared with segments above the site of injury, the intensity of HO-1 immunostaining and the number of HO-1 positive neurons in the ventral horn motor neurons were prominently increased in segments below the injury. Western blot analysis confirmed the observations. HO-2 protein was mapped to the ventral horn motor neurons, oligodendrocytes, the Clarke's nucleus neurons and the ependymal cells. When compared with segments below the site of injury, neuronal HO-2 staining intensity was increased above the site of injury, and most notably at 16 h. These observations were also confirmed by western blotting and HO activity measurements. Tissue Fe3+ and cGMP staining were increased and prominently mapped below the site of injury, where cGMP colocalized with HO-1 in the nucleus of the motor neurons. Also, a site of injury-directed pattern of induction of FADD, TRAIL, and p53 immunoreactivity, and a widespread colocalization of the oncogenes with HO-1 protein, were found within motor neurons below the level of injury. We forward the hypothesis that HO-1 and HO-2 have different roles in the defense mechanisms of the injured nervous system. We hypothesize that HO-1 protects against further damage by contributing to controlled cell death through their intrinsic suicide program, while HO-2 is involved in suppression of inflammatory response by NO derived radicals. PMID- 11208918 TI - Modulation of electrically evoked acetylcholine release in cultured rat septal neurones. AB - The electrically evoked release of acetylcholine and its modulation via auto- and heteroreceptors were studied in primary cell cultures prepared from embryonic rat septum (ED 17). Cultures were grown for 1, 2 or 3 weeks on circular, poly D lysine-coated glass coverslips. They developed a dense network of non-neuronal and neuronal cells, only some of which were immunopositive for choline acetyltransferase. To measure acetylcholine release, the cells on the coverslips were pre-incubated with [3H]choline (0.1 micromol/L), superfused with modified Krebs-Henseleit buffer at 25 degrees C and electrically stimulated twice for 2 min (S1, S2; 3 Hz, 0.5 ms, 90-100 mA). The electrically evoked overflow of [3H] from the cells consisted of approximately 80% of authentic [3H]Ach, was largely Ca2+-dependent and tetrodotoxin sensitive, and hence represents an action potential-evoked, exocytotic release of acetylcholine. Using pairs of selective agonists and antagonist added before S2, muscarinic autoreceptors, as well as inhibitory adenosine A1- and opioid mu-receptors, could be detected, whereas delta-opioid receptors were not found. Evoked [3H] overflow from cultures grown for 1 week, although Ca2+ dependent and tetrodotoxin sensitive, was insensitive to the muscarinic agonist oxotremorine, whereas the effect of oxotremorine on cells grown for 3 weeks was even more pronounced than that in 2-week-old cultures. In conclusion, similar to observations on rat septal tissue in vivo, acetylcholine release from septal cholinergic neurones grown in vitro is inhibited via muscarinic, adenosine A1 and mu-opioid receptors. This in vitro model may prove useful in the exploration of regulatory mechanisms underlying the expression of release modulating receptors on septal cholinergic neurones. PMID- 11208919 TI - Increased levels of oxidative stress markers detected in the brains of mice devoid of prion protein. AB - Although minor abnormalities have been reported in prion protein (PrP) knock-out (Prnp-/-) mice, the normal physiological function of PrP, the causative agent implicated in transmissible spongiform encephalopathies (TSE), remains unresolved. Since there are increasing correlations between oxidative stress and amyloidoses, we decided to investigate whether PrP plays a role in oxidative modulation. We found higher levels of oxidative damage to proteins and lipids in the brain lysates of Prnp-/- as compared to wild-type (WT) mice of the same genetic background. These two indicators, protein oxidation and lipid peroxidation, are hallmarks of cellular oxidative damage. Elevated levels of ubiquitin-protein conjugates were also observed in Prnp-/- mice, a probable consequence of cellular attempts to remove the damaged proteins as indicated by increased proteasome activity. Taken together, these findings are indicative of a role for PrP in oxidative homeostasis in vivo. PMID- 11208920 TI - Inhibition of insulin-like growth factor-1 receptor and IRS-2 signaling by ethanol in SH-SY5Y neuroblastoma cells. AB - The effect of ethanol on insulin-like growth factor-1 (IGF-I)-mediated signal transduction and functional activation in neuronal cells was examined. In human SH-SY5Y neuroblastoma cells, ethanol inhibited tyrosine autophosphorylation of the IGF-I receptor. This corresponded to the inhibition of IGF-I-induced phosphorylation of p42/p44 mitogen-activated/extracellular signal-regulated protein kinase (MAPK) by ethanol. Insulin-related substrate-2 (IRS-2) and focal adhesion kinase phosphorylation were reduced in the presence of ethanol, which corresponded to the prevention of lamellipodia formation (30 min). By contrast, ethanol had no effect on Shc phosphorylation when measured up to 1 h, and did not affect the association of Grb-2 with Shc. Neurite formation at 24 h was similarly unaffected by ethanol. The data indicate that the IGF-I receptor is a target for ethanol in SH-SY5Y cells However, there is diversity in the sensitivity of signaling elements within the IGF-I receptor tyrosine kinase signaling cascades to ethanol, which can be related to the inhibition of specific functional events in neuronal activation. PMID- 11208921 TI - Aging alters regional multichemical profile of the human brain: an in vivo 1H-MRS study of young versus middle-aged subjects. AB - Age-related differences in the multichemical proton magnetic resonance spectroscopy (1H-MRS) profile of the human brain have been reported for several age groups, and most consistently for ages from neonates to 16-year-olds. Our recent 1H-MRS study demonstrated a significant age-related increase of total chemical concentration (relative to creatine) in the prefrontal and sensorimotor cortices within young adulthood (19-31-year-olds). In the present study we test the hypothesis that the level of brain chemicals in the same cortices, which show increased chemical levels during normal development, are reduced with normal aging after young adulthood. The multichemical 1H-MRS profile of the brain was compared between 19 young and 16 middle-aged normal subjects across multiple brain regions for all chemicals of 1H-MRS spectra. Chemical concentrations were measured relative to creatine. Over all age groups the total relative chemical concentration was highest in the prefrontal cortex. Middle-aged subjects demonstrated a significant decrease of total relative chemical concentration in the dorsolateral prefrontal (F = 54.8, p < 10(-7), ANOVA), orbital frontal (F = 3.7, p < 0.05) and sensorimotor (F = 15.1, p < 0.0001) cortices, as compared with younger age. Other brain regions showed no age-dependent differences. The results indicate that normal aging alters multichemical 1H-MRS profile of the human brain and that these changes are region-specific, with the largest changes occuring in the dorsolateral prefrontal cortex. These findings provide evidence that the processes of neuronal maturation of the human brain, and neurotransmitters and other chemical changes as the marker of these neuronal changes are almost finished by young adulthood and then reduced during normal aging toward middle age period of life. The present data also support the notion of heterochronic regressive changes of the aging human brain, where the multichemical brain regional profile seems to inversely recapitulate cortical chemical maturation within normal development. PMID- 11208922 TI - Gas chromatography-mass spectrometry analysis of endogenous cannabinoids in healthy and tumoral human brain and human cells in culture. AB - Endocannabinoids are lipid mediators thought to modulate central and peripheral neural functions. We report here gas chromatography-electron impact mass spectrometry analysis of human brain, showing that lipid extracts contain anandamide and 2-arachidonoylglycerol (2-AG), the most active endocannabinoids known to date. Human brain also contained the endocannabinoid-like compounds N oleoylethanolamine, N-palmitoylethanolamine and N-stearoylethanolamine. Anandamide and 2-AG (0.16 +/- 0.05 and 0.10 +/- 0.05 nmol/mg protein, respectively) represented 7.7% and 4.8% of total endocannabinoid-like compounds, respectively. N-Palmitoyethanolamine was the most abundant (50%), followed by N oleoyl (23.6%) and N-stearoyl (13.9%) ethanolamines. A similar composition in endocannabinoid-like compounds was found in human neuroblastoma CHP100 and lymphoma U937 cells, and also in rat brain. Remarkably, human meningioma specimens showed an approximately six-fold smaller content of all N acylethanolamines, but not of 2-AG, and a similar decrease was observed in a human glioblastoma. These ex vivo results fully support the purported roles of endocannabinoids in the nervous system. PMID- 11208923 TI - Antiapoptotic role of NF-kappaB in the auto-oxidized dopamine-induced apoptosis of PC12 cells. AB - Current concepts of the pathogenesis of Parkinson's disease (PD) center on the formation of reactive oxygen species (ROS), and dopamine has been considered to be a major source of ROS. Recently, it has been shown in a postmortem study that nuclear translocation of nuclear factor-kappa B (NF-kappaB) was observed in dopaminergic neurons of patient with PD. However, its role is not known. The present study examined the possible role of NF-kappaB in ODA (auto-oxidized dopamine)-induced apoptosis to understand the process of PD. Using the electrophoretic mobility shift assay, it was found that ODA activated the DNA binding activity of NF-kappaB. Suppression of the transcriptional activity of NF kappaB in PC12 cells by overexpression of a wild-type and a dominant negative mutant form (S32A/S36A) of inhibitor kappa B (IkappaB)-alpha led to increase of apoptotic cell death induced by treatment of ODA. In addition, overexpression of NF-kappaB in PC12 cells blocked ODA-induced cell death. However, JNK/SAPK activities, which mediate various stress signals, were similar among the parental, NF-kappaB- or dominant negative mutant IkappaB alpha-transfected cells. Therefore, these results suggest that activation of NF-kappaB during ODA-induced apoptosis may have a counteracting activity against the signals mediating apoptotic cell death and thereby delay the process of Parkinson's disease. PMID- 11208925 TI - Brain-derived neurotrophic factor mediates an excitoprotective effect of dietary restriction in mice. AB - Dietary restriction (DR; reduced calorie intake) increases the lifespan of rodents and increases their resistance to cancer, diabetes and other age-related diseases. DR also exerts beneficial effects on the brain including enhanced learning and memory and increased resistance of neurons to excitotoxic, oxidative and metabolic insults. The mechanisms underlying the effects of DR on neuronal plasticity and survival are unknown. In the present study we show that levels of brain-derived neurotrophic factor (BDNF) are significantly increased in the hippocampus, cerebral cortex and striatum of mice maintained on an alternate day feeding DR regimen compared to animals fed ad libitum. Damage to hippocampal neurons induced by the excitotoxin kainic acid was significantly reduced in mice maintained on DR, and this neuroprotective effect was attenuated by intraventricular administration of a BDNF-blocking antibody. Our findings show that simply reducing food intake results in increased levels of BDNF in brain cells, and suggest that the resulting activation of BDNF signaling pathways plays a key role in the neuroprotective effect of DR. These results bolster accumulating evidence that DR may be an effective approach for increasing the resistance of the brain to damage and enhancing brain neuronal plasticity. PMID- 11208924 TI - Phosphatidylinositol 3-kinase activity is required for the expression of glial fibrillary acidic protein upon cAMP-dependent induction of differentiation in rat C6 glioma. AB - Glial fibrillary acidic protein (GFAP) is an intermediate filament (IF) protein expressed upon maturation of astrocytes and upregulated during reactive astrogliosis. Its expression is modulated by several growth factors and hormones. Although an upregulation of intracellular cAMP is required for the induction of GFAP expression in astrocytes, little information is available on other downstream factors of the signal transduction pathways involved in the regulation of its expression. In this communication, we identified phosphatidylinositol 3 kinase (PI 3-K) as a necessary enzyme for GFAP expression in rat C6 glioma cells. Use of the specific PI 3-K inhibitors wortmannin and LY294002 and transfection of C6 cells with a dominant negative PI 3-K construct, resulting in a decrease of the enzymatic activity of PI 3-K, inhibited the cAMP-dependent expression of GFAP. Furthermore, confocal laser scanning microscopy demonstrated that inhibition of the PI 3-K activity by LY294002 or wortmannin concomitant with induction of differentiation changes the cellular distribution leading to a pericentrosomal localization of GFAP and an altered cell shape lacking process formation. We conclude that the expression and cellular distribution of GFAP is mediated through a PI 3-K-dependent mechanism. PMID- 11208927 TI - Oxidative post-translational modifications of alpha-synuclein in the 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. AB - Structural and functional alterations of alpha-synuclein is a presumed culprit in the demise of dopaminergic neurons in Parkinson's disease (PD). Alpha-synuclein mutations are found in familial but not in sporadic PD, raising the hypothesis that effects similar to those of familial PD-linked alpha-synuclein mutations may be achieved by oxidative post-translational modifications. Here, we show that wild-type alpha-synuclein is a selective target for nitration following peroxynitrite exposure of stably transfected HEK293 cells. Nitration of alpha synuclein also occurs in the mouse striatum and ventral midbrain following administration of the parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP). Conversely, beta-synuclein and synaptophysin were not nitrated in MPTP-intoxicated mice. Our data demonstrate that alpha-synuclein is a target for tyrosine nitration, which, by disrupting its biophysical properties, may be relevant to the putative role of alpha-synuclein in the neurodegeneration associated with MPTP toxicity and with PD. PMID- 11208931 TI - Helen T. Parsons (1886-1977). PMID- 11208926 TI - The multidrug resistance protein MRP1 mediates the release of glutathione disulfide from rat astrocytes during oxidative stress. AB - The release of glutathione disulfide has been considered an important process for the maintenance of a reduced thiol redox potential in cells during oxidative stress. In cultured rat astrocytes, permanent hydrogen peroxide-induced oxidative stress caused a rapid increase in intracellular glutathione disulfide, which was followed by the appearance of glutathione disulfide in the medium. Under these conditions, the viability of the cells was not compromised. In the presence of cyclosporin A and the quinoline-derivative MK571, inhibitors of multidrug resistance proteins (MRP1 and MRP2), glutathione disulfide accumulated in cells and the release of glutathione disulfide from astrocytes during H2O2 stress was potently inhibited, suggesting a contribution of MRP1 or MRP2 in the release of glutathione disulfide from astrocytes. Using RT-PCR we amplified a cDNA from astroglial RNA with a high degree of homology to MRP1 from humans and mouse. In contrast, no fragment was amplified by using primers specific for rat MRP2. In addition, the presence of MRP1 protein in astrocytes was demonstrated by its immunolocalization in cells expressing the astroglial marker protein glial fibrillary acidic protein. Our data identify rat astrocytes as a MRP1-expressin, brain cell type and demonstrate that this transporter participates in the release of glutathione disulfide from astrocytes during oxidative stress. PMID- 11208932 TI - Guinea pigs as models for cholesterol and lipoprotein metabolism. AB - Guinea pigs carry the majority of their plasma cholesterol in LDL, making them a unique animal model with which to study hepatic cholesterol and lipoprotein metabolism. In this review, the benefits and advantages of using this particular model are discussed. How dietary factors such as soluble fiber, cholesterol and fatty acids that vary in saturation and chain length affect hepatic cholesterol homeostasis and influence the synthesis, intravascular processing and catabolism of lipoproteins is reviewed. In addition, alterations in hepatic cholesterol metabolism and plasma lipoproteins as affected by treatment with cholestyramine or 3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitors, exercise, marginal intake of vitamin C, ovariectomy (a model for menopause) and similarities to the human situation are addressed. A review of guinea pigs as models for early atherosclerosis development is also presented. PMID- 11208933 TI - Short-term zinc deficiency affects nuclear factor-kappab nuclear binding activity in rat testes. AB - We reported previously that feeding zinc-deficient diets for 14 d altered the oxidant defense system in the testes of young male rats and increased levels of lipid, protein and DNA oxidation in this tissue. In this study, we investigated the early involvement of oxidative stress in zinc deficiency-induced testicular pathology. Weanling male rats (17 d old) were given free access to a control (25 microg Zn/g) or a zinc-deficient (0.5 microg Zn/g) diet, or restricted access to the control diet at a level of intake similar to that of rats fed the 0.5 microg Zn/g diet (restricted group) for 7 d. Rats fed the low zinc diet were characterized by low testes zinc and alkaline phosphatase activity compared with ad libitum and restricted controls. Testes protein and lipid oxidation variables did not differ among the groups. Higher than normal (P < 0.05) activities of CuZn (CuZnSOD) and Mn (MnSOD) superoxide dismutases were observed in the low zinc group. Glutathione peroxidase and glutathione reductase activities did not differ among the groups. Total glutathione concentrations were lower in the low zinc and restricted groups than in the control group (P < 0.05). The testes nuclear binding activities of two transcription factors sensitive to oxidants [nuclear factor (NF)-kappaB and AP-1] were assessed. AP-1 nuclear binding activity did not differ among the groups, but NF-kappaB nuclear binding activity was lower in the low zinc group than in the control groups (P < 0.05). We suggest that the reduction in NF-kappaB binding reflects an early response to zinc deficiency induced oxidative stress. PMID- 11208934 TI - Tea catechins prevent the development of atherosclerosis in apoprotein E deficient mice. AB - Green tea contains various antioxidative flavan-3ols (tea catechins), such as (-) epigallocatechin gallate (EGCg, the major catechin), which exert potent inhibitory effects on LDL oxidation in vitro and ex vivo in humans. In this study, the antiatherogenic effects of tea catechins were examined in atherosclerosis-susceptible C57BL/6J, apoprotein (apo)E-deficient mice. Male apoE deficient mice (10 wk old) were fed an atherogenic diet for 14 wk; during that time, one group (tea) was supplied drinking water supplemented with green tea extract (0.8 g/L), and another group (control) was offered the vehicle only. The tea extract consisted of the following (g/100 g): EGCg, 58.4; (-) epigallocatechin (EGC), 11.7; (-)-epicatechin (EC), 6.6; (-)-gallocatechingallate (GCg), 1.6; (-)-epicatechin gallate (ECg), 0.5; and caffeine, 0.4. The estimated actual intake of tea catechin was 1.7 mg/(d. mouse). Tea ingestion did not influence plasma cholesterol or triglyceride concentrations. Plasma lipid peroxides were reduced in the tea group at wk 8, suggesting that the in vivo oxidative state is improved by tea ingestion. Atheromatous areas in the aorta from the arch to the femoral bifurcation and aortic weights were both significantly attenuated by 23% in the tea group compared with the control group. Aortic cholesterol and triglyceride contents were 27 and 50% lower, respectively, in the tea group than in the control group. These results suggest that chronic ingestion of tea extract prevents the development of atherosclerosis without changing the plasma lipid level in apoE-deficient mice, probably through the potent antioxidative activity of the tea. PMID- 11208935 TI - Folate depletion and elevated plasma homocysteine promote oxidative stress in rat livers. AB - This study was designed to determine whether nutritional folate depletion exerts hepatic oxidative stress in relation to elevated plasma homocysteine. To mimic various extents of folate depletion status in vivo, male Wistar rats were fed an amino acid-defined diet containing either 8 (control), 2, 0.5, or 0 mg folic acid/kg diet. After a 4-wk feeding period, the plasma and hepatic folate concentrations of the rats decreased significantly with each decrement of dietary folate. Folate depletion did not significantly affect two major liver antioxidants: reduced glutathione and alpha-tocopherol. Conversely, folate depletion decreased Cu-Zn superoxide dismutase and glutathione peroxidase activities, but had no effect on catalase activity in liver homogenates. Lipid peroxidation products, as measured by thiobarbituric acid-reactive substances, were significantly higher in livers of folate-depleted rats than in those of the controls. This occurrence of hepatic oxidative stress in folate-depleted rats was confirmed by demonstrating an increased susceptibility of livers of folate depleted rats to lipid peroxidation induced by additional H2O2 or Fe(2+) treatments compared with the controls. Decreasing dietary folate intake resulted in graded increases in plasma homocysteine concentrations of folate-depleted rats. Elevated plasma homocysteine and decreased plasma and hepatic folate concentrations in folate-depleted rats were all strongly and significantly correlated with increased liver lipid peroxidation (/r/ > or = 0.58, P < 0.0003). These data demonstrate that folate depletion and elevated plasma homocysteine promote oxidative stress in rat livers. PMID- 11208936 TI - A polyunsaturated fatty acid diet lowers blood pressure and improves antioxidant status in spontaneously hypertensive rats. AB - gamma-Linolenic acid [GLA, 18:3(n-6)], eicosapentaenoic acid [EPA, 20:5(n-3)] and docosahexaenoic acid [DHA, 22:6(n-3)] have been reported to prevent cardiovascular diseases. However, they are highly unsaturated and therefore more sensitive to oxidation damage. We investigated the effects of a diet rich in these polyunsaturated fatty acids (PUFA) on blood pressure, plasma and lipoprotein lipid concentrations, total antioxidant status, lipid peroxidation and platelet function in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Five-week-old SHR and WKY rats were fed for 10 wk either a diet containing Isio 4 oil or a diet rich in GLA, EPA and DHA (5.65, 6.39 and 4.94 g/kg dry diet, respectively). The total antioxidant status was assayed by monitoring the rate of free radical-induced hemolysis. VLDL-LDL sensitivity to copper-induced lipid peroxidation was determined as the production of thiobarbituric acid reactive substances. After dietary PUFA supplementation, a significant decrease in blood pressure of SHR rats (-20 mm Hg) was observed and the total antioxidant status was enhanced. VLDL-LDL resistance to copper-induced peroxidation was increased in both strains. The PUFA supplementation did not change platelet maximum aggregation in SHR rats, but it decreased the aggregation speed. In hypertensive rats, GLA + EPA + DHA supplementation lowers blood pressure, enhances total anti-oxidant status and resistance to lipid peroxidation, diminishes platelet aggregation speed and lowers plasma lipid concentrations. Thus, it enhances protection against cardiovascular diseases. Therefore, nutritional recommendations for cardiovascular disease prevention should take into account the pharmacologic properties of GLA, EPA and DHA. PMID- 11208937 TI - Differential regulation of zinc transporter 1, 2, and 4 mRNA expression by dietary zinc in rats. AB - Zinc metabolism is well regulated over a wide range of dietary intakes to help maintain cellular zinc-dependent functions. Expression of transporter molecules, which influence zinc influx and efflux across the plasma and intracellular membranes, contributes to this regulation. We have examined in rats the comparative response of zinc transporters 1, 2, and 4 (ZnT-1, ZnT-2 and ZnT-4) to dietary zinc. ZnT-1 and ZnT-4 are expressed ubiquitously, whereas ZnT-2 is limited to small intestine, kidney, placenta and, in some cases, the liver. When zinc intake was low (<1 mg Zn/kg), ZnT-2 mRNA was extremely low in small intestine and kidney compared with an adequate intake (30 mg Zn/kg). ZnT-1 and ZnT-2 mRNAs were markedly greater in both tissues when a supplemental zinc intake (180 mg Zn/kg) was provided. ZnT-4 was refractory to changes in zinc intake. When zinc was provided as a single oral dose (70 mg/kg body), ZnT-1 and ZnT-2 mRNA levels were increased many fold in small intestine, liver and kidney, whereas ZnT 4 gene expression was not changed. The expression of ZnT-1 and ZnT-2 is comparable to zinc-induced changes in metallothionein mRNA levels, suggesting a similar mode of regulation for these genes. The relative differential in regulation by zinc is ZnT-2 > ZnT-1 > ZnT-4. These data provide evidence that, in an animal model, zinc transporter expression is responsive to zinc under physiologically relevant conditions. PMID- 11208938 TI - Energy requirements of lactating women derived from doubly labeled water and milk energy output. AB - Instead of using an incremental approach to assess the energy requirements of lactation, a more comprehensive approach may be taken by measuring total energy expenditure (TEE), milk energy output and energy mobilization from tissue stores. The latter approach avoids assumptions regarding energetic efficiency and changes in physical activity and adiposity. The purpose of this study was threefold: to assess the energy requirements of lactation; to compare these estimates with energy requirements in the nonpregnant, nonlactating state and to test for energetic adaptations in basal metabolic rate (BMR) and physical activity during the energy-demanding process of lactation. Milk production and composition, body weight and composition, TEE, BMR and physical activity levels were measured in 24 well-nourished women during exclusive breastfeeding at 3 mo postpartum and after the cessation of breastfeeding at 18 or 24 mo postpartum. TEE was measured by the doubly labeled water method, milk production by 3-d test-weighing, milk energy by bomb calorimetry on a 24-h milk sample, body composition by dual-energy x-ray absorptiometry and BMR by room respiration calorimetry. TEE, BMR and physical activity level (physical activity level = TEE/BMR) did not differ between the lactating and nonlactating state (TEE 10.0 +/- 1.5 versus 10.6 +/- 2.1 MJ/d). Mean milk energy output was equivalent to 2.02 +/- 0.33 MJ/d. Total energy requirements were greater during lactation than afterward (12.0 +/- 1.4 versus 10.6 +/- 2.1 MJ/d, P: = 0.002). Energy mobilization from tissue stores (-0.65 +/- 0.97 MJ/d) resulted in net energy requirements during lactation of 11.4 +/- 1.8 MJ/d. Because adaptations in basal metabolism and physical activity were not evident in these well-nourished women, energy requirements during lactation were met primarily from the diet and only partially by mobilization of tissue stores. PMID- 11208939 TI - The metabolic availability of dietary triacylglycerols from two high oleic oils during the postprandial period does not depend on the amount of oleic acid ingested by healthy men. AB - Monounsaturated oils, virgin olive oil (VOO) and high oleic sunflower oil (HOSO) are suggested to have selective physiologic effects on humans in the fasting state. The aim of the study was to evaluate whether two oils with equal amounts of oleic acid but with different compositions of minor fatty acids and triacylglycerol molecular species (TAG) could produce different triacylglycerol rich lipoprotein (TRL)-TAG responses in the postprandial state. Eight normolipidemic men consumed the following three meals in random order on separate occasions with 2 wk between meals: control meal, control meal plus VOO and control meal plus HOSO. Plasma total TAG and TRL-TAG were measured hourly for 7 h after ingestion. TAG and sn-2 positional fatty acids within TAG were analyzed in the TRL fraction. Plasma total TAG concentrations in response to the dietary oils did not differ. However, TRL triglyceridemia was significantly lower after VOO intake (P < 0.05). The molecular species in the TRL fraction returned toward basal levels more quickly (P < 0.05) after VOO than HOSO intake. 2-Positional fatty acid analysis demonstrated higher proportions of stearic and palmitic acids and a lower proportion of oleic acid (P < 0.05) in TRL-TAG derived from HOSO. This study shows that VOO intake results in attenuated postprandial TAG concentration and faster TRL-TAG disappearance from blood compared with HOSO, suggesting that the oleic acid content may not be the main factor affecting TAG metabolism. Minor fatty acids such as linoleic acid and the 2-positional distribution of saturated stearic and palmitic acids into the TAG molecule may be important determinants of postprandial lipemia in normolipidemic men. PMID- 11208940 TI - Chlorogenic acid and caffeic acid are absorbed in humans. AB - Chlorogenic acid, an ester of caffeic acid and quinic acid, is a major phenolic compound in coffee; daily intake in coffee drinkers is 0.5-1 g. Chlorogenic acid and caffeic acid are antioxidants in vitro and might therefore contribute to the prevention of cardiovascular disease. However, data on the absorption of chlorogenic acid and caffeic acid in humans are lacking. We determined the absorption of chlorogenic acid and caffeic acid in a cross-over study with 4 female and 3 male healthy ileostomy subjects. In such subjects, degradation by the colonic microflora is minimal and absorption can be calculated as the amount ingested minus the amount excreted in ileostomy effluent. The ileostomy subjects ingested 2.8 mmol chlorogenic acid and 2.8 mmol caffeic acid on separate days in random order and subsequently collected ileostomy fluid and urine for 24 h. Absorption of chlorogenic acid was 33 +/- 17% (mean +/- SD) and of caffeic acid 95 +/- 4%. Traces of the ingested chlorogenic acid and 11% of the ingested caffeic acid were excreted in urine. Thus, one third of chlorogenic acid and almost all of the caffeic acid were absorbed in the small intestine of humans. This implies that part of chlorogenic acid from foods will enter into the blood circulation, but most will reach the colon. PMID- 11208941 TI - Cognitive and motor functions of iodine-deficient but euthyroid children in Bangladesh do not benefit from iodized poppy seed oil (Lipiodol). AB - Iodine supplementation before pregnancy in iodine-deficient women prevents cretinism and neuromotor deficits in their offspring. It is unclear whether iodine supplementation benefits cognitive function in iodine-deficient school aged children. We therefore conducted a double-blind, randomized, controlled trial of the effects of iodized poppy seed oil (Lipiodol) on cognitive and motor function and weight gain of iodine-deficient school children. The study was conducted with 305 children in grades 1 and 2 from 10 primary schools in two iodine-deficient areas in Bangladesh. The children were stratified by school and grade and randomly assigned to receive 400 mg of oral Lipiodol or a placebo. All children were given a battery of cognitive and motor function tests and had their weights, serum thyroxine (T4) and thyroid-stimulating hormone (TSH) and urinary iodine levels measured before and 4 mo after the intervention. On enrollment, both groups were moderately iodine deficient (median urinary iodine values: placebo group = 3.3 micromol/L, n = 148; iodine group = 3.1 micromol/L, n = 152; goiter prevalence in both groups >95%). However, their T4 and TSH levels were within the normal range. After 4 mo, there was a significant treatment effect on urinary iodine levels (P < 0.0001), but the levels of the treated group were still below normal (median = 7.9 micromol/L). No significant differences were found in T4 and TSH levels, weight gain, cognitive or motor function. The findings suggest that Lipiodol supplementation in moderately iodine-deficient children with normal T4 levels is unlikely to benefit their cognitive function. However, it remains possible that other iodine preparations may have benefits. PMID- 11208942 TI - Breast-feeding has a limited long-term effect on anthropometry and body composition of Brazilian mothers. AB - The effect of lactation on maternal nutrition is controversial. Some studies have shown that breast-feeding reduces maternal weight, whereas some have not. All studies have been restricted to the first 2 y after delivery. We investigated the effect of lactation on maternal nutrition 5 y after delivery. All mothers giving birth in the city of Pelotas, Brazil, in 1993 were interviewed and weighed soon after delivery; information was also obtained on prepregnancy weight. In 1994, information on breast-feeding duration and pattern was collected for a 20% subsample. They were seen again in 1998, and those eligible (nonsmokers, no subsequent pregnancy, last birth weight > or = 2500 g) underwent measurements for weight, height, waist, hip and arm circumferences, triceps and subscapular skinfolds. The following indices were calculated in 312 women: body mass index, waist/hip ratio, arm fat area, the percentage of body fat assessed through skinfolds, and weight and body mass index change since before conception. The percentage of body fat was also measured through bioimpedance for half of the sample. After adjustment for confounding, all outcomes generally showed a similar pattern, i.e., mothers who breast-fed for 6-11.9 mo had lower measurements than those with shorter or longer durations. However, only the association with bioimpedance was significant (P < 0.03), and that for arm fat area tended to be significant (P = 0.06). Exclusive or predominant breastfeeding at 4 mo was associated with lower waist circumference (P = 0.05) and the percentage of body fat measured through skinfolds (P = 0.04). This study suggests that the relationship between breast-feeding and long-term changes in maternal weight is complex and, in this population, not particularly strong. PMID- 11208943 TI - Metabolic evidence for adaptation to a high protein diet in rats. AB - This study was designed to assess the effects of long-term adaptation to a high protein diet on energy intake, body weight gain, body composition and splanchnic metabolic indicators in rats. For this purpose, adult male Wistar rats were fed either a 50 g/100 g dry matter (DM) protein diet (P50 group) or a 14 g/100 g DM protein diet (P14 group) for 21 d. These two groups were compared with a P14 pair fed (P14-pf) group that consumed the same daily energy as the P50 group. The energy intake of the P50 group was 16 +/- 1% less than that of the P14 group (P < 0.05), and the P50 group had significantly lower body weight. The P50 group had significantly less adipose tissue compared with both P14 and P14-pf rats. The activities of the brush border membrane enzymes, neutral aminopeptidase and gamma glutamyl transferase, were significantly higher in the P50 group than in the P14 rats. Similarly, the activities of alanine aminotransferase, arginase and serine dehydratase were significantly higher in the liver of P50 rats compared with P14 rats. Both amino acid transporter system A and X(A,G-) activities, measured in freshly isolated hepatocytes, were significantly higher in the P50 group (8- and 1.5-fold, P < 0.05, respectively) compared with the P14 group. The 1.5-fold increase in the steady-state activity of X(A,G-) was accompanied by a doubling of EAAT2 mRNA, involved in the system X(A,G-). This study provides confirmation that specific biochemical and molecular adaptive processes of the splanchnic area are involved in the response to variations in the protein content of the diet. PMID- 11208944 TI - High glycemic index starch promotes hypersecretion of insulin and higher body fat in rats without affecting insulin sensitivity. AB - In rats, prolonged feeding of high glycemic index (GI) starch results in basal hyperinsulinemia and an elevated insulin response to an intravenous glucose tolerance test (IVGTT). The aim of this study was to assess hepatic and peripheral insulin resistance (IR) using euglycemic hyperinsulinemic clamps. Insulin sensitivity, epididymal fat deposition and fasting leptin concentrations were compared in rats fed isocalorically a low or high GI diet for 7 wk (45% carbohydrate, 35% fat and 20% protein as energy) or a high fat diet (20% carbohydrate, 59% fat and 21% protein as energy) for 4 wk so that final body weights were similar. At the end of the study, high GI rats had higher basal leptin concentration and epididymal fat mass than the low GI group, despite comparable body weights. High GI and high fat feeding both resulted in the higher insulin response during IVGTT, but impaired glucose tolerance was seen only in rats fed high fat. The GI of the diet did not affect basal and clamp glucose uptake or hepatic glucose output, but high fat feeding induced both peripheral and hepatic IR. The findings suggest that hypersecretion of insulin without IR may be one mechanism for increased fat deposition in rats fed high GI diets. PMID- 11208945 TI - Food deprivation exacerbates mitochondrial oxidative stress in rat liver exposed to ischemia-reperfusion injury. AB - Mitochondria undergo oxidative damage during reperfusion of ischemic liver. Although nutritional status affects ischemia-reperfusion injury in the liver, its effect on mitochondrial damage has not been evaluated. Thus, this study was designed to determine whether starvation influences the oxidative balance in mitochondria isolated from livers exposed to warm ischemia-reperfusion. Fed and 18- and 36-h food-deprived rats underwent partial hepatic ischemia followed by reperfusion. Mitochondria were isolated before and after ischemia and during reperfusion. Serum alanine transaminase was measured to assess liver injury. The mitochondrial concentrations of malondialdehyde, protein carbonyls and glutathione were determined as indicators of oxidative injury. Cell ultrastructure was assessed by transmission electron microscopy. Transaminase levels were greater in 18-h food-deprived than fed rats (after 120 min of reperfusion: 3872 +/- 400 vs. 1138 +/- 59 U/L, P < 0.01). Mitochondrial glutathione was lower in food-deprived than fed rats before and after ischemia, and during reperfusion. Food deprivation also was associated with significantly greater lipid and protein oxidative damage. Finally, more ultrastructural damage was observed during reperfusion in mitochondria from food-deprived rats. Prolonging the length of food deprivation to 36 h exacerbated significantly both the mitochondrial oxidative injury and the release of serum transaminases in rats (after 120 min of reperfusion: 5438 +/- 504 U/L, P < 0.01). Food deprivation was associated with greater mitochondrial oxidative injury in rat livers exposed to warm ischemia-reperfusion, and the extent of oxidative damage in mitochondria increased with the length of food deprivation. PMID- 11208947 TI - Dietary fatty acid composition in pregnancy alters neurite membrane fatty acids and dopamine in newborn rat brain. AB - The importance of maternal dietary fatty acids on arachidonic acid [AA; 20:4(n 6)] and docosahexaenoic acid [DHA; 22:6(n-3)] in fetal brain nerve growth cone membranes and monoaminergic neurotransmitters was investigated. Rats were fed purified diets containing 20 g/100 g safflower oil with 74.3% 18:2(n-6), 0.2% 18:3(n-3), soybean oil with 55.4% 18:2(n-6), 7.7% 18:3(n-3) or high fish oil with 24.6% 22:6(n-3) through gestation. Tissue for rats within a litter were pooled at birth, brain growth cone membranes prepared and phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylinositol (PI) fatty acids quantified by gas-liquid chromatography. Dopamine, serotonin, and the metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid, and 5 hydroxyindolacetic acid were quantified by HPLC. Growth cone membranes from offspring of rats fed safflower oil had significantly lower, and offspring of rats fed high 22:6(n-3) fish oil had significantly higher 22:6(n-3) in PE, PS and PI than the soybean oil group. The growth cone membrane PC, PE and PS 20:4(n-6) was significantly lower in the fish oil than in the soybean or safflower oil groups. Serotonin concentration was significantly higher in brain of offspring in the safflower oil compared with the soybean oil group. The newborn brain dopamine was inversely related to PE DHA and PS DHA (P < 0.001), but positively related to PC AA (P < 0.05). These studies show that maternal dietary fatty acids may alter fetal brain growth cone (n-6) and (n-3) fatty acids, and neurotransmitters involved in neurite extension, target finding and synaptogenesis. The functional importance, however, is not known at this time. PMID- 11208946 TI - Food supplementation with milk fermented by Lactobacillus casei DN-114 001 protects suckling rats from rotavirus-associated diarrhea. AB - Group A rotavirus is the leading cause of diarrhea among children aged 3-36 mo worldwide. Introducing fermented milk products into the infant diet has been proposed for the prevention or treatment of rotavirus diarrhea. The preventive effect of milk fermented by the Lactobacillus casei strain DN-114 001 was studied in a model of germfree suckling rats supplemented daily from d 2 of life and infected with SA11 rotavirus at d 5 (RF group). One group was supplemented with nonfermented milk (RM) and two uninfected groups (CM and CF) received either nonfermented or fermented milk. Frequency and severity of diarrhea were observed. Rats were killed at various times from 0 to 120 h postinfection (p.i.). Bacteria were measured in the intestine, and rotavirus antigens were detected by ELISA in fecal samples and in different parts of the intestine. Histologic observations were made, including vacuolation, morphology of intestinal villi and number of mucin cells. RM rats had diarrhea for 6 d; compared with the CM group, they had alterations of the intestinal mucosa characterized by cellular vacuolation 48 and 72 h p.i. and a lower number of sulfated mucin cells 72 and 96 h p.i. (P: < 0.05). Early supplementation with fermented milk significantly decreased the clinical signs of diarrhea from 24 to 144 h p.i. (P: < 0.05) and prevented rotavirus infection in all sections of the intestine. Histologic lesions of the small intestine were greatly reduced (P: < 0.05) and the number of mucin cells remained unchanged. The data are discussed with respect to the possibility of reducing rotavirus diarrhea in young children by consumption of fermented milk. PMID- 11208948 TI - 17-beta-estradiol affects brain protein synthesis rate in ovariectomized female rats. AB - The purpose of this study was to determine whether 17-ss-estradiol affects the rate of brain protein synthesis in ovariectomized female rats. Experiments were conducted on three groups of 12-wk-old female rats: group 1 were ovariectomized to reduce the level of plasma estradiol, group 2 were ovariectomized and treated with estradiol and group 3 were sham-operated controls. The fractional rates of protein synthesis in brain of ovariectomized rats treated with estradiol were significantly greater than that in ovariectomized rats without estradiol treatment. In the cerebral cortex and cerebellum, the RNA activity [g protein synthesized/(g RNA. d)] significantly correlated (r > 0.87, P < 0.001) with the fractional rate of protein synthesis. The RNA concentration (mg RNA/g protein) was not related to the fractional rate of protein synthesis in any organ. The results suggest that estrogen treatment of ovariectomized female rats is likely to increase the rate of protein synthesis in the brain and that RNA activity is at least in part related to the fractional rate of brain protein synthesis. PMID- 11208949 TI - Wheat aleurone flour increases cecal beta-glucuronidase activity and butyrate concentration and reduces colon adenoma burden in azoxymethane-treated rats. AB - Processed wheat aleurone flour (WAF) is a source of insoluble fermentable dietary fiber that comes from the outer layers of the wheat kernel. A study was designed to evaluate WAF, wheat bran (WB) and alpha-cellulose as the source of dietary fiber (5 g/100 g of diet) in a semipurified high fat (20 g/100 g of as 1:1 lard/sunflower seed oil) diet fed to male Sprague-Dawley rats in which intestinal tumors were induced using azoxymethane (AOM). WAF at 33 g/100 g of diet (WAF33) and WB at 16 g/100 g of diet (WB16) increased the weight of feces and produced significantly higher concentrations in the cecum of the short-chain fatty acid butyrate (P < 0.001) than did no fiber (NF) and WAF added at only 10 g/100 g (1.5 g of dietary fiber) (WAF10). Cecal and fecal pH were both significantly lower in the WAF33 and WB16 treatments relative to control and no fiber treatments (P < 0.001). The intestinal tumors in the rats were assessed at 6 mo after the study began, and the WAF33- or WB16-fed rats showed a trend (P = 0.06) with 43% fewer colon adenomas relative to control. There was a significant inverse relationship between ss-glucuronidase activity and colon adenomas in the rat colon (r2 = 0.37, P = 0.001). WAF fiber influenced some metabolic markers of fermentation in the colon in a manner similar to that of WB, which, independent of the bulking effect, was associated with a trend to reduced colon adenomas. Significantly increased cecal ss-glucuronidase activity and/or butyrate concentrations may have protective influences in this context by mechanisms not yet fully elucidated. PMID- 11208950 TI - Revision 2000: a statement for healthcare professionals from the Nutrition Committee of the American Heart Association. PMID- 11208953 TI - Maternal and prepubertal diet, mammary development and breast cancer risk. AB - At present, we do not know what causes sporadic breast cancer. Environmental factors,particularly diet, appear to explain at least 70% of newly diagnosed breast cancers, but it is not clear what these factors are. We propose that the lack of progress in this area is due to a lack of considering the effect of timing of environmental and dietary exposures on the breast. The evidence provided above suggests that an in utero exposure to an estrogenic environment including that caused by diet [high (n-6) PUFA or genistein]-increases breast cancer risk. This increase may be mediated by an increased presence of TEB in the mammary epithelial tree and increased ER-alpha levels, reduced ER-beta levels or both. Prepubertal estrogenic exposure, in contrast, reduces later risk of developing breast cancer. The protective effect of estrogens may be mediated by early epithelial differentiation, reduced presence of ER-alpha and increased levels of ER-beta in the mammary gland. The challenge we are now facing is to determine whether the data obtained mainly through the use of animal models is relevant to women and if so, how we might be able to modulate pregnancy and childhood estrogenic exposure by appropriate dietary modifications to reduce breast cancer risk in women. PMID- 11208954 TI - Evaluation of the in vitro and in vivo antitumor activities of vitamin C and K-3 combinations against human prostate cancer. PMID- 11208955 TI - Vitamin E: mechanisms of action as tumor cell growth inhibitors. PMID- 11208956 TI - PC-SPES and prostate cancer. PMID- 11208957 TI - Role of gap-junctional communication in breast cancer progression and chemoprevention. PMID- 11208958 TI - The European Prospective Investigation into Cancer and Nutrition (EPIC): plans and progress. PMID- 11208959 TI - Clinical trials of breast and prostate cancer prevention. PMID- 11208960 TI - Evaluation of botanicals and dietary supplements therapy in cancer patients. PMID- 11208961 TI - Dietary change and cancer: challenges and future direction. PMID- 11208966 TI - Integrins: the missing link. PMID- 11208967 TI - Pore properties and ionic block of the rabbit epithelial calcium channel expressed in HEK 293 cells. AB - We have used the whole-cell patch-clamp technique to analyse the permeation properties and ionic block of the epithelial Ca2+ channel ECaC heterologously expressed in human embryonic kidney (HEK) 293 cells. Cells dialysed with 10 mM BAPTA and exposed to Ca2+-containing, monovalent cation-free solutions displayed large inwardly rectifying currents. Their reversal potential depended on the extracellular Ca2+ concentration, [Ca2+]o. The slope of the relationship between reversal potential and [Ca2+]o on a logarithmic scale was 21 +/- 4 mV, compared with 29 mV as predicted by the Nernst equation (n = 3-5 cells). Currents in mixtures of Ca2+ and Na+ or Ca2+ and Ba2+ showed anomalous mole fraction behaviour. We have described the current-concentration plot for Ca2+ and Na+ by a kinetic permeation model, i.e. the "step" model. Extracellular Mg2+ blocked both divalent and monovalent currents with an IC50 of 62 +/- 9 microM(n = 4) in Ca2+ free conditions and 328 +/- 50 microM (n = 4-9) in 100 microM Ca2+ solutions. Mono- and divalent currents through ECaCs were blocked by gadolinium, lanthanum and cadmium, with a blocking order of Cd2+ >> Gd3+ > La3+. We conclude that the permeation of monovalent and divalent cations through ECaCs shows similarities with L-type voltage-gated Ca2+ channels, the main differences being a higher Ca2+ affinity and a significantly higher current density in micromolar Ca2+ concentrations in the case of ECaCs. PMID- 11208968 TI - Angiotensin II inhibits rat arterial KATP channels by inhibiting steady-state protein kinase A activity and activating protein kinase Ce. AB - We used whole-cell patch clamp to investigate steady-state activation of ATP sensitive K+ channels (KATP) of rat arterial smooth muscle by protein kinase A (PKA) and the pathway by which angiotensin II (Ang II) inhibits these channels. Rp-cAMPS, an inhibitor of PKA, did not affect KATP currents activated by pinacidil when the intracellular solution contained 0.1 mM ATP. However, when ATP was increased to 1.0 mM, inhibition of PKA reduced KATP current, while the phosphatase inhibitor calyculin A caused a small increase in current. Ang II (100 nM) inhibited KATP current activated by the K+ channel opener pinacidil. The degree of inhibition was greater with 1.0 mM than with 0.1 mM intracellular ATP. The effect of Ang II was abolished by the AT1 receptor antagonist losartan. The inhibition of KATP currents by Ang II was abolished by a combination of PKA inhibitor peptide 5-24 (5 microM) and PKC inhibitor peptide 19-27 (100 microM), while either alone caused only partial block of the effect. In the presence of PKA inhibitor peptide, the inhibitory effect of Ang II was unaffected by the PKC inhibitor Go 6976, which is selective for Ca2+-dependent isoforms of PKC, but was abolished by a selective peptide inhibitor of the translocation of the epsilon isoform of PKC. Our results indicate that KATP channels are activated by steady state phosphorylation by PKA at normal intracellular ATP levels, and that Ang II inhibits the channels both through activation of PKCepsilon and inhibition of PKA. PMID- 11208969 TI - Agents that increase tyrosine phosphorylation activate a non-selective cation current in single rabbit portal vein smooth muscle cells. AB - The effects of agents that increase tyrosine phosphorylation were studied with whole-cell recording of membrane currents in single smooth muscle cells from the rabbit portal vein. In K+-free conditions with the chloride equilibrium potential at about -50 mV, intracellular application via the patch pipette of 200 microM sodium orthovanadate (Na3VO4), which inhibits tyrosine phosphatases, activated a "noisy" inward current at a holding potential of -50 mV. Intracellular dialysis with 100 microM (pY)EEI, a peptide activator of the cytosolic tyrosine kinase pp60c-src, and bath application of 5 microM insulin, which activates receptor coupled tyrosine kinases, also evoked a "noisy" inward current. The current voltage relationships and the reversal potential (about +10 mV) of the Na3VO4-, pp60c-src- and insulin-induced currents were similar to those of the noradrenaline-evoked non-selective cation current (Icat). The inward currents evoked by noradrenaline, Na3VO4, (pY)EEI and insulin were all greatly potentiated when the bathing calcium concentration was reduced from 1.5 mM to 50 microM. The single channel conductance estimated from spectral density analysis of the whole cell current was about 20 pS for noradrenaline, Na3VO4, (pY)EEI and insulin. Moreover for all agents the spectra were described by the sum of two Lorentzians with similar corner frequencies. Noradrenaline-evoked Icat was inhibited to a similar degree by the tyrosine kinase inhibitors genistein and tyrphostin 23 and their inactive analogues daidzein and tyrphostin A1, respectively. In the presence of Na3VO4, application of noradrenaline evoked a cation current of similar peak amplitude to control Icat although the rate of decay of Icat was enhanced in the presence of Na3VO4. This study shows that stimulation of both cytosolic and receptor-coupled tyrosine kinases evokes a non-selective cation current and the conductance is similar to that activated by noradrenaline. PMID- 11208970 TI - Proton sensitivity of rat cerebellar granule cell GABAA receptors: dependence on neuronal development. AB - The effect of GABAA receptor development in culture on the modulation of GABA induced currents by external H+ was examined in cerebellar granule cells using whole-cell and single-channel recording. Equilibrium concentration-response curves revealed a lower potency for GABA between 11 and 12 days in vitro (DIV) resulting in a shift of the EC50 from 10.7 to 2.4 uM. For granule cells before 11 DIV, the peak GABA-activated current was inhibited at low external pH and enhanced at high pH with a pKa of 6.6. For the steady-state response, low pH was inhibitory with a pKa of 5.56. After 11 DIV, the peak GABA-activated current was largely pH insensitive; however, the steady-state current was potentiated at low pH with a pKa of 6.84. Single GABA-activated ion channels were recorded from outside-out patches of granule cell bodies. At pH 5.4-9.4, single GABA channels exhibited multiple conductance states occurring at 22-26, 16-17 and 12-14 pS. The conductance levels were not significantly altered over the time period of study, nor by changing the external H+ concentration. Two exponential functions were required to fit the open-time frequency histograms at both early (< 11 DIV) and late (> 11 DIV) development times at each H+ concentration. The short and long open time constants were unaffected either by the extracellular H+ concentration or by neuronal development. The distribution of all shut times was fitted by the sum of three exponentials designated as short, intermediate and long. At acidic pH, the long shut time constant decreased with development as did the relative contribution of these components to the overall distribution. This was concurrent with an increase in the mean probability of channel opening. In conclusion, this study demonstrates in cerebellar granule cells that external pH can either reduce, have no effect on, or enhance GABA-activated responses depending on the stage of development, possibly related to the subunit composition of the GABAA receptors. The mode of interaction of H+ at the single-channel level and implications of such interactions at cerebellar granule cell GABAA receptors are discussed. PMID- 11208971 TI - Effect of extracellular Ca2+ on the quinine-activated current of bullfrog taste receptor cells. AB - The bitter substance quinine activates a cation current from the frog taste receptor cell. We have analysed the noise associated with this current, and the effect of extracellular Ca2+ on the current, using whole-cell recording on single dissociated cells. Quinine induced an inward current from the taste receptor cell near the resting potential. The response was accompanied by an increase in current fluctuations. From the variance/mean ratio of the quinine-activated current, the single-channel conductance was estimated to be 12 pS in the nominal absence of extracellular Ca2+. In the presence of 1.8 mM Ca2+, this conductance decreased to 5 pS. These values broadly agree with those previously obtained from excised, outside-out membrane patches. The dependence of the current on quinine concentration had a K1/2 of 0.48 mM in the absence of extracellular Ca2+, consistent with measurements from excised patches. The K1/2 value increased to 2.8 mM in 1.8 mM external Ca2+. The maximum current induced by quinine was also reduced by about 20% by Ca2+. The spectral power density distribution of the quinine-activated current could be described by the sum of two Lorentzian functions, with corner frequencies not substantially different in the absence and presence of 1.8 mM external Ca2+. The above results lend further support to the notion that the major component of the response of frog taste receptor cells to quinine comes from an ion channel directly activated by quinine. PMID- 11208972 TI - Hypertonic enhancement of transmitter release from frog motor nerve terminals: Ca2+ independence and role of integrins. AB - Hyperosmotic solutions cause markedly enhanced spontaneous quantal release of neurotransmitter from many nerve terminals. The mechanism of this enhancement is unknown. We have investigated this phenomenon at the frog neuromuscular junction with the aim of determining the degree to which it resembles the modulation of release by stretch, which has been shown to be mediated by mechanical tension on integrins. The hypertonicity enhancement, like the stretch effect, does not require Ca2+ influx or release from internal stores, although internal release may contribute to the effect. The hypertonicity effect is sharply reduced (but not eliminated) by peptides containing the RGD sequence, which compete with native ligands for integrin bonds. There is co-variance in the magnitude of the stretch and osmotic effects; that is, individual terminals exhibiting a large stretch effect also show strong enhancement by hypertonicity, and vice versa. The stretch and osmotic enhancements also can partially occlude each other. There remain some clear-cut differences between osmotic and stretch forms of modulation: the larger range of enhancement by hypertonic solutions, the relative lack of effect of osmolarity on evoked release, and the reported higher temperature sensitivity of osmotic enhancement. Nevertheless, our data strongly implicate integrins in a significant fraction of the osmotic enhancement, possibly acting via the same mechanism as stretch modulation. PMID- 11208973 TI - Insulin-like growth factor I alters renal function and stimulates renin secretion in late gestation fetal sheep. AB - While it is known that treatment with insulin-like growth factor I (IGF-I) stimulates growth of the fetal kidney, nothing is known about the short term or long term effects of IGF-I on fetal renal function. To investigate the acute effects of IGF-I on fetal renal function and on the activity of the fetal renin angiotensin system, studies were carried out in 12 chronically catheterized fetal sheep aged 120 +/- 1 days, before and during a 4 h I.V. infusion of IGF-I at 80 ug h-1. Seven control fetuses were infused over the same period with vehicle (0.1% bovine serum albumin in 0.15 M saline). IGF-I infusion increased plasma IGF I concentrations by about 80%. There was a small fall in arterial PO2 (P < 0.01), arterial PCO2 increased (P < 0.05), plasma lactate levels increased (P < 0.01) and arterial pH fell (P < 0.05). Fractional bicarbonate reabsorption increased and bicarbonate excretion decreased (P < 0.05). Infusions of IGF-I had no sustained effect on fetal arterial pressure. Glomerular filtration rate (GFR) did not change significantly during IGF-I infusion, but renal blood flow (RBF) fell (P < 0.05). Therefore filtration fraction relative to control values increased (P < 0.05), suggesting that efferent arteriolar vasoconstriction had occurred. IGF-I infusion led to an antidiuresis (P < 0.01), a rise in urinary osmolality (P < 0.05) and a fall in free water clearance (P < 0.01). Since fetal PO2 fell, it is probable that these effects were mediated by arginine vasopressin. The excretion rates of sodium, chloride and phosphate were all reduced by 4 h of infusion (P < 0.05), because their fractional reabsorption rates were all increased (sodium, P < 0.01; chloride, P < 0.01; and phosphate, P < 0.05). Plasma renin concentration increased by 275 +/- 52% during infusion of IGF-I (P < 0.005). Plasma renin activity also increased (P < 0.005), while circulating angiotensinogen concentrations fell (P < 0.05). In the adult, IGF-I increases both RBF and GFR, enhances tubular reabsorption and stimulates the renin-angiotensin system. In the fetus, however, it decreased RBF and had no effect on GFR, but was associated with enhanced tubular function and intense stimulation of renin secretion. Some of these effects of IGF-I on fetal renal function may be involved in maturation of the kidney in preparation for life after birth. PMID- 11208974 TI - Cross-bridge interaction kinetics in rat myocardium are accelerated by strong binding of myosin to the thin filament. AB - To determine the ability of strong-binding myosin cross-bridges to activate the myocardial thin filament, we examined the Ca2+ dependence of force and cross bridge interaction kinetics at 15 degrees C in the absence and presence of a strong-binding, non-force-generating derivative of myosin subfragment-1 (NEM-S1) in chemically skinned myocardium from adult rats. Relative to control conditions, application of 6 microM NEM-S1 significantly increased Ca2+-independent tension, measured at pCa 9.0, from 0.8 +/- 0.3 to 3.7 +/- 0.8 mN mm-2. Furthermore, NEM-S1 potentiated submaximal Ca2+-activated forces and thereby increased the Ca2+ sensitivity of force, i.e. the [Ca2+] required for half-maximal activation (pCa50) increased from pCa 5.85 +/- 0.05 to 5.95 +/- 0.04 (change in pCa50 (dpCa50) = 0.11 +/- 0.02). The augmentation of submaximal force by NEM-S1 was accompanied by a marked reduction in the steepness of the force-pCa relationship for forces less than 0.50 Po (maximum Ca2+-activated force), i.e. the Hill coefficient (n2) decreased from 4.72 +/- 0.38 to 1.54 +/- 0.07. In the absence of NEM-S1, the rate of force redevelopment (ktr) was found to increase from 1.11 +/- 0.21 s-1 at submaximal [Ca2+] (pCa 6.0) to 9.28 +/- 0.41 s-1 during maximal Ca2+ activation (pCa 4.5). Addition of NEM-S1 reduced the Ca2+ dependence of ktr by eliciting maximal values at low levels of Ca2+, i.e. ktr was 9.38 +/- 0.30 s-1 at pCa 6.6 compared to 9.23 +/- 0.27 s-1 at pCa 4. At intermediate levels of Ca2+, ktr was less than maximal but was still greater than values obtained at the same pCa in the absence of NEM-S1. NEM-S1 dramatically reduced both the extent and rate of relaxation from steady-state submaximal force following flash photolysis of the caged Ca2+ chelator diazo-2. These data demonstrate that strongly bound myosin cross-bridges increase the level of thin filament activation in myocardium, which is manifested by an increase in the rate of cross-bridge attachment, potentiation of force at low levels of free Ca2+, and slowed rates of relaxation. PMID- 11208975 TI - Origin and propagation of spontaneous excitation in smooth muscle of the guinea pig urinary bladder. AB - The origin and propagation of waves of spontaneous excitation in bundles of smooth muscle of the guinea-pig bladder were examined using intracellular recording techniques and visualization of the changes in the intracellular calcium concentration ([Ca2+]i). Bladder smooth muscle cells exhibited spontaneous transient increases in [Ca2+]i which originated along a boundary of each smooth muscle bundle and then spread to the other boundary with a conduction velocity of 2.0 1r1r>mm1> s-1. Spontaneous increases in [Ca2+]i were always preceded by action potentials. Nifedipine (10 microM) abolished increases in both [Ca2+]i and action potentials. Caffeine (10 1s1sFmM1F), ryanodine (50 microM) and cyclopiazonic acid (10 microM reduced the amplitude of the associated increases in [Ca2+]i without preventing the generation of action potentials. Spontaneous action potentials had conduction velocities of 40 1t1t>mm 1> s-1 in the axial direction and 1.3 1u1u>mm 1> s-1 in the transverse direction. The electrical length constants of the bundles of muscle were 425 microM in the axial direction and 12.5 microM in the transverse direction. Neurobiotin, injected into an impaled smooth muscle cell, spread more readily to neighbouring cells located in the axial direction than those located in the transverse direction. The spread of neurobiotin was inhibited by 18beta-glycyrrhetinic acid (18beta-GA, 40 microM), a gap junction blocker. Immunohistochemistry for Connexin 43 showed abundant punctate staining on the smooth muscle cell membranes. These results suggested that spontaneous action potentials and associated calcium waves occur almost simultaneously along the boundary of bladder smooth muscle bundles and then propagate to the other boundary probably through gap junctions. PMID- 11208976 TI - Optical recordings of taste responses from fungiform papillae of mouse in situ. AB - Single taste buds in mouse fungiform papillae consist of approximately 50 elongated cells (TBCs), where fewer than three TBCs have synaptic contacts with taste nerves. We investigated whether the non-innervated TBCs were chemosensitive using a voltage-sensitive dye, tetramethylrhodamine methyl ester (TMRM), under in situ optical recording conditions. Prior to the optical recordings, we investigated the magnitude and polarity of receptor potentials under in situ whole-cell clamp conditions. In response to 10 mM HCl, several TBCs were depolarized by approximately 25 mV and elicited action potentials, while other TBCs were hyperpolarized by approximately 12 mV. The TBCs eliciting hyperpolarizing receptor potentials also generated action potentials on electrical stimulation. A mixture of 100 mM NaCl, 10 mM HCl and 500 mM sucrose depolarized six TBCs and hyperpolarized another three TBCs out of 13 identified TBCs in a taste bud viewed by optical section. In an optical section of another taste bud, 1 M NaCl depolarized five TBCs and hyperpolarized another two TBCs out of 11 identified TBCs. The number of chemosensitive TBCs was much larger than the number of innervated TBCs in a taste bud, indicating the existence of chemosensitivity in non-innervated TBCs. There was a tendency for TBCs eliciting the same polarity of receptor potential to occur together in taste buds. We discuss the role of non-innervated TBCs in taste information processing. PMID- 11208977 TI - Role of muscle tone in peristalsis in guinea-pig small intestine. AB - We investigated the involvement of muscle tone and circular muscle (CM) contraction in peristalsis in isolated guinea-pig small intestine. A segment of jejunum (approximately 13 cm) was mounted into a three chambered partitioned bath. Peristaltic waves were initiated in the oral chamber either by: (1) infusing fluid into the oral end of the jejunum; the ejected fluid was diverted via a cannula from reaching the intermediate and anal chambers, or by (2) intraluminal balloon distension of the empty oral segment. Tension of the circular muscle was measured in all three chambers. Peristaltic waves elicited by fluid infusion were evoked at an abrupt threshold. In contrast, peristaltic waves elicited by distension could be graded in amplitude according to stimulus intensity. Peristaltic waves evoked in an empty intestine exhibited similar propagation velocities to peristaltic waves associated with fluid propulsion. Nifedipine (200-400 nM) added to the intermediate chamber to block muscle contraction did not prevent peristaltic waves elicited by either stimulus from propagating into the anal chamber, although their amplitude was attenuated. Nifedipine to the site of stimulation (oral chamber) abolished peristaltic waves generated by either stimulus. Tetrodotoxin (1-2 microM), or a low Ca2+-high Mg2+ solution to the intermediate chamber abolished the propagation of peristalsis from the oral to anal chambers. In conclusion, graded peristaltic waves can occur in an empty intestine. Therefore peristalsis is not necessarily an "all-or-none" phenomenon. Peristalsis depends on the spread of nervous activity along the bowel, rather than the reactivation of neural circuits caused by displacement of fluid in the lumen. However, local muscle tone and contraction are important for the initiation and maintenance of peristaltic propagation. PMID- 11208978 TI - Interactions between two different inhibitory systems in the human motor cortex. AB - Intracortical inhibition in the human motor cortex has been previously demonstrated using paired-pulse transcranial magnetic stimulation (TMS) protocols at short intervals (1-6 ms; short interval intracortical inhibition, SICI) with a subthreshold conditioning pulse preceding a suprathreshold test pulse, and at long intervals (50-200 ms; long interval intracortical inhibition, LICI) with suprathreshold conditioning and test pulses. We investigated whether different circuits mediate these inhibitory phenomena and how they interact. In nine healthy volunteers, we applied TMS to the motor cortex and recorded motor evoked potentials from the first dorsal interosseous muscle. With increasing test pulse strength, LICI decreases but SICI tends to increase. There was no correlation between the degree of SICI and LICI. We tested the interactions between SICI and LICI. SICI was reduced or eliminated in the presence of LICI. Loss of SICI was seen even with a conditioning stimulus too weak to induce significant LICI. Our findings demonstrate that different cell populations mediate SICI and LICI. The results are consistent with the hypothesis that LICI inhibits SICI through presynaptic GABAB receptors. Testing of SICI in the presence of LICI may be a non invasive way of evaluating inhibitory interactions in the human motor cortex. PMID- 11208979 TI - Respiratory effects of the external and internal intercostal muscles in humans. AB - The current conventional view of intercostal muscle actions is based on the theory of Hamberger (1749) and maintains that as a result of the orientation of the muscle fibres, the external intercostals have an inspiratory action on the lung and the internal interosseous intercostals have an expiratory action. Recent studies in dogs, however, have shown that this notion is only approximate. In the present studies, the respiratory actions of the human external and internal intercostal muscles were evaluated by applying the Maxwell reciprocity theorem. Thus the orientation of the muscle fibres relative to the ribs and the masses of the muscles were first assessed in cadavers. Five healthy individuals were then placed in a computed tomographic scanner to determine the geometry of the ribs and their precise transformation during passive inflation to total lung capacity. The fractional changes in length of lines with the orientation of the muscle fibres were then computed to obtain the mechanical advantages of the muscles. These values were finally multiplied by muscle mass and maximum active stress (3.0 kg cm-2) to evaluate the potential effects of the muscles on the lung. The external intercostal in the dorsal half of the second interspace was found to have a large inspiratory effect. However, this effect decreases rapidly in the caudal direction, in particular in the ventral portion of the ribcage. As a result, it is reversed into an expiratory effect in the ventral half of the sixth and eighth interspaces. The internal intercostals in the ventral half of the sixth and eighth interspaces have a large expiratory effect, but this effect decreases dorsally and cranially. The total pressure generated by all the external intercostals during a maximum contraction would be -15 cmH2O, and that generated by all the internal interosseous intercostals would be +40 cmH2O. These pressure changes are substantially greater than those induced by the parasternal intercostal and triangularis sterni muscles, respectively. PMID- 11208981 TI - How well do we manage and support patients and families with dominantly inherited renal disease? PMID- 11208980 TI - Exercising skeletal muscle blood flow in humans responds to reduction in arterial oxyhaemoglobin, but not to altered free oxygen. AB - We hypothesised that reducing arterial oxyhaemoglobin (O2Hba) with carbon monoxide (CO) in both normoxia and hyperoxia, or acute hypoxia would cause similar compensatory increases in human skeletal muscle blood flow and vascular conductance during submaximal exercise, despite vast differences in arterial free oxygen partial pressure (Pa,O2). Seven healthy males completed four 5 min one legged knee-extensor exercise bouts in the semi-supine position (30 +/- 3 W, mean +/- S.E.M.), separated by approximately 1 h of rest, under the following conditions: (a) normoxia (O2Hba = 195 ml l-1; Pa,O2 = 105 mmHg); (b) hypoxia (163 ml l-1; 47 mmHg); (c) CO + normoxia (18% COHba; 159 ml l-1; 119 mmHg); and (d) CO + hyperoxia (19% COHba; 158 ml l-1; 538 mmHg). CO + normoxia, CO + hyperoxia and systemic hypoxia resulted in a 29-44% higher leg blood flow and leg vascular conductance compared to normoxia (P < 0.05), without altering blood pH, blood acid-base balance or net leg lactate release. Leg blood flow and leg vascular conductance increased in association with reduced O2Hba (r2 = 0.92-0.95; P < 0.05), yet were unrelated to altered Pa,O2. This association was further substantiated in two subsequent studies with graded increases in COHba (n = 4) and NO synthase blockade (n = 2) in the presence of normal Pa,O2. The elevated leg blood flow with CO + normoxia and CO + hyperoxia allowed a approximately 17% greater O2 delivery (P < 0.05) to exercising muscles, compensating for the lower leg O2 extraction (61%) compared to normoxia and hypoxia (69%; P < 0.05), and thereby maintaining leg oxygen uptake constant. The compensatory increases in skeletal muscle blood flow and vascular conductance during exercise with both a CO load and systemic hypoxia are independent of pronounced alterations in Pa,O2 (47-538 mmHg), but are closely associated with reductions in O2Hba. These results suggest a pivotal role of O2 bound to haemoglobin in increasing skeletal muscle vasodilatation during exercise in humans. PMID- 11208982 TI - Imaging techniques for the detection of vesicoureteric reflux: what and when? PMID- 11208983 TI - Keep your temper: how to avoid heat accumulation in haemodialysis. PMID- 11208984 TI - Should relative blood volume changes be routinely measured during the dialysis session? PMID- 11208985 TI - Recent issues concerning renal transplantation in systemic lupus erythematosus patients. PMID- 11208986 TI - Obesity as a risk factor in renal transplant patients. PMID- 11208987 TI - Sirolimus: a new promising immunosuppressive drug. Towards a rationale for its use in renal transplantation. PMID- 11208988 TI - Novel approaches to the non-invasive diagnosis of coronary-artery disease. PMID- 11208990 TI - Association of nitric oxide production and apoptosis in a model of experimental nephropathy. AB - BACKGROUND: In recent studies increased amounts of nitric oxide (NO) and apoptosis have been implicated in various pathological conditions in the kidney. We have studied the role of NO and its association with apoptosis in an experimental model of nephrotic syndrome induced by a single injection of adriamycin (ADR). METHODS: The alteration in the NO pathway was assessed by measuring nitrite levels in serum/urine and by evaluating the changes in vascular reactivity of the isolated perfused rat kidney (IPRK) system. Rats were stratified into control groups and ADR-induced nephropathy groups. These two groups were then divided into: group 1, animals receiving saline; and group 2, animals receiving aminoguanidine (AG) which is a specific inhibitor of inducible NO synthase. On day 21, rats were sacrificed after obtaining material for biochemical analysis. RESULTS: Histopathological examination of the kidneys of rats treated with ADR revealed focal areas of mesangial proliferation and mild tubulointerstitial inflammation. They also had significantly higher levels of proteinuria compared with control and treatment groups (P < 0.05). Urine nitrite levels were significantly increased in the ADR-nephropathy group (P < 0.05). In the IPRK phenylephrine and acetylcholine related responses were significantly impaired in the ADR-nephropathy group. Apoptosis was not detected in controls. However, in the ADR-nephropathy group, numerous apoptotic cells were identified in the tubulointerstitial areas. Double staining revealed numerous interstitial apoptotic cells to stain for ED1, a marker for monocytes/macrophages. Treatment with AG prevented the impairment of renal vascular bed responses and reduced both urine nitrite levels and apoptosis to control levels. CONCLUSION: We suggest that interactions between NO and apoptosis are important in the pathogenesis of the ADR-induced nephrosis. PMID- 11208991 TI - Analysis of anti-neutrophil cytoplasmic antibodies (ANCA): frequency and specificity in a sample of 191 homozygous (PiZZ) alpha1-antitrypsin-deficient subjects. AB - BACKGROUND: ANCA are autoantibodies directed against polymorphonuclear cell antigens, mainly proteinase 3 (PR3) and myeloperoxidase (MPO), which are implicated in the pathogenesis of small-vessel necrotizing vasculitis. Alpha1 antitrypsin is the main inhibitor of neutral serine proteinase [i.e. human leukocyte elastase (HLE) and PR3] present in PMN alpha-granules (alphaGr). An association first reported by us between PR3 ANCA and the deficient PiZZ phenotype in ANCA-positive systemic vasculitis, now widely confirmed by others, led us to study the incidence and specificity of ANCA among PiZZ subjects. METHODS: We tested a population of 191 PiZZ (273 sera) for ANCA activity versus 272 PiMM matched control subjects using alphaGr or antigen-specific ELISA [PR3, HLE, MPO, lactoferin (LF) and bactericidal/ permeability increasing protein (BPI)]. RESULTS: The incidence of antibodies directed against alphaGr and HLE but not PR3, MPO, LF or BPI was increased in the PiZZ as compared to the PiMM group (Fisher probability respectively P < 0.0001 and P < 0.05). CONCLUSIONS: ANCA not directed against classical antigens (MPO and PR3) may be found in PiZZ patients. However, these patients do not develop systemic vasculitis features. Therefore, alpha1-antitrypsin deficiency is not sufficient to induce ANCA positive vasculitides, and may only act as a second hit amplifying factor. PMID- 11208992 TI - Plasma total homocysteine concentration in nephrotic patients with idiopathic membranous nephropathy. AB - BACKGROUND: The atherothrombotic risk pattern of the nephrotic syndrome resembles that of hyperhomocysteinemia. However, the effect of nephrotic range proteinuria on homocysteine metabolism has never been studied. METHODS: The study included 11 male nephrotic patients with idiopathic membranous nephropathy who underwent a treatment trial with adrenocorticotrophic hormone and 11 male non-nephrotic, renal function-matched control subjects. The nephrotic patients were studied before and after the treatment, which induced a marked reduction in urinary protein excretion and a moderate improvement in renal function in all cases. RESULTS: Plasma total homocysteine (tHcy) concentration did not change significantly during treatment, whereas the nephrotic patients had significantly lower tHcy than the non-nephrotic patients (14.2 +/- 3.4 micromol/l vs 19.0 +/- 5.4 micromol/l). tHcy correlated significantly with serum concentrations of creatinine (r = 0.53, P < 0.05) and albumin (r = 0.43, P < 0.05), glomerular filtration rates (GFRs) (iohexol clearances) (r = -0.42, P < 0.05) and urinary albumin excretion (r = -0.47, P < 0.05). CONCLUSION: The expected tHcy-lowering effect of improved renal function may have masked a tHcy-elevating effect due to reduced proteinuria leading to no net change in tHcy during treatment. The notion of an increase in tHcy associated with remission of the nephrotic syndrome is in accordance with the significantly lower tHcy in the nephrotic renal patients compared with the non-nephrotic renal function-matched patients, and the relationships between tHcy and serum albumin concentrations as well as urinary albumin excretion. Thus, the results of this small study suggest that nephrotic range proteinuria directs homocysteine metabolism towards a decrease in tHcy. However, the findings need to be confirmed in larger patient populations and in different varieties of the nephrotic syndrome. PMID- 11208993 TI - Autosomal recessive hypophosphataemic rickets with hypercalciuria is not caused by mutations in the type II renal sodium/phosphate cotransporter gene. AB - BACKGROUND: At present the genetic defect for autosomal recessive and autosomal dominant hypophosphataemic rickets with hypercalciuria (HHRH) is unknown. Type II sodium/phosphate cotransporter (NPT2) gene is a serious candidate for being the causative gene in either or both autosomal recessive and autosomal dominant HHRH. In the present study we tested this hypothesis in one autosomal recessive family. METHODS: The gene structure of human NPT2 is known. We tested the complete open reading frame in the affected siblings by polymerase chain reaction in combination with automatic DNA sequencing for the presence of mutations. RESULTS: We did not observe disease-causing mutations in the NPT2 gene of the affected siblings. A T855C polymorphism resulting in a histidine to arginine transition was present in the open reading frame of NPT2. The polymorphism was present in both affected as well as unaffected family members. CONCLUSION: The hypothesis that a defect in the NPT2 gene could be an underlying cause for autosomal recessive HHRH could not be sustained in our study. PMID- 11208994 TI - Conservative treatment and anti-reflux surgery in adults with vesico-ureteral reflux: effect on urinary-tract infections, renal function and loin pain in a long-term follow-up study. AB - STUDY PURPOSE: To investigate the long-term effects in adults of conservative treatment and anti-reflux surgery for vesico-ureteral reflux on urinary-tract infections, renal function, and loin pain. METHODS: Of 115 adult patients with vesico-ureteral reflux diagnosed between 1968 and 1984, conservative treatment was given to 46 patients (36 women) and anti-reflux surgery was performed in 57 patients (52 women). The remaining 12 patients underwent nephrectomy or heminephrectomy and were excluded from the study. The anti-reflux surgical methods used were the Politano-Leadbetter procedure in 44 patients (73 ureters) and the Hutch procedure in 19 patients (25 ureters). Six of these patients were operated on with both methods. RESULTS: The frequency of acute pyelonephritis was significantly reduced after anti-reflux surgery (P < 0.0001) as well as after diagnosis of vesico-ureteral reflux in the group given conservative treatment (P or < 0.001). The frequency of lower-urinary-tract infections was not altered in either group. Surgery had no effect on significant albuminuria (Albustix > or = 2+) or on progressive renal functional deterioration. Forty-three patients reported recurrent loin pain at the time of diagnosis or anti-reflux surgery. Only one of the 12 patients in the conservative group, compared with 29 of the 31 patients in the anti-reflux surgery group, obtained relief from loin pain during the follow-up. Nine patients in the anti-reflux surgery group reported restitution of reduced general well-being after surgery. These patients had experienced weariness and/or headache before surgery. Vesico-ureteral reflux was eliminated more frequently (P < 0.01) in the patients operated on by the Politano Leadbetter procedure (94%) than in those operated on by the Hutch procedure (68%). CONCLUSIONS: Loin pain is common in adults with vesico-ureteral reflux and is effectively eliminated by anti-reflux surgery. Anti-reflux surgery should be considered in adults with vesico-ureteral reflux and very frequent acute pyelonephritic attacks only if conservative treatment has failed to alleviate these symptoms. Anti-reflux surgery is not indicated with the aim of arresting renal functional deterioration. PMID- 11208996 TI - Autonomic neuropathy is linked to nocturnal hypoxaemia and to concentric hypertrophy and remodelling in dialysis patients. AB - BACKGROUND: Autonomic dysfunction and sleep apnoea are frequent complications of chronic renal failure. Since nocturnal hypoxaemia in sleep apnoea dampens autonomic reflexes, we postulated that altered autonomic control is in part linked to nocturnal hypoxaemia in uraemic patients. METHODS: To test the hypothesis we performed continuous monitoring of O(2) saturation during night by pulse oximetry (Ohmeda-Biox) as well as echocardiography, 24-h ambulatory blood pressure monitoring, and standard tests of autonomic function in 50 patients on chronic dialysis (40 on haemodialysis and 10 on CAPD). For haemodialysis patients all studies were performed during a mid-week non-dialysis day. RESULTS: Twenty five patients had at least one episode of nocturnal hypoxaemia (median 13, interquartile range 4-31) while the other 25 patients had no episodes at all. Minimal and average SaO(2) were strongly interrelated (r = 0.64, P = 0.0001). In a multiple regression model, besides age, average nocturnal SaO(2) was the only independent predictor of the parasympathetic function. Similarly, average nocturnal SaO(2) was the only independent predictor of the autonomic response to standing. Sex, 24-h mean arterial pressure, body mass index, haematocrit, serum albumin, serum parathyroid hormone and duration of dialysis treatment had no independent effect on the autonomic tests. Interestingly, the average nocturnal SaO(2) and the interaction between the responses to the autonomic tests were independently related to posterior-wall thickness. This interaction term represented also the stronger independent predictor of the relative wall thickness of the left ventricle. In a multiple logistic regression model the interaction parasympathetic-sympathetic function was the only independent predictor of concentric remodelling or hypertrophy, while average nocturnal SaO(2) entered into this model (P = 0.03) only after exclusion of the autonomic function interaction term. CONCLUSIONS: Thus, altered cardiovascular autonomic control appears to be linked to nocturnal hypoxaemia and to concentric hypertrophy or remodelling in dialysis patients. Since nocturnal hypoxaemia is an established cardiovascular risk factor, altered autonomic control is a potential mechanism whereby hypoxaemia may trigger cardiovascular events in dialysis patients. It remains to be seen whether the link between nocturnal hypoxaemia and autonomic dysfunction is a causal one. PMID- 11208995 TI - Malnutrition in long-term haemodialysis survivors. AB - BACKGROUND: Long survival is now common in patients with end-stage renal disease owing to improvement in dialysis techniques and kidney transplantation. As malnutrition is commonly reported in dialysis patients, we evaluated the nutritional status of patients treated with haemodialysis (HD) for more than 20 years. METHODS: Ten patients (59.5 years old; 4F/6M; HD treatment for 304 months; group A) underwent an extensive nutritional examination and were compared to a control group of 10 patients treated with HD for an average of 51 months and strictly matched for age (58.6 years old), gender, and height (group B). The patients were treated on a similar basis (long-duration HD, cellulosic membranes, Daugirdas index >2). RESULTS: The body weight (BW) in group A had decreased gradually from the 11th year of HD treatment, whereas it had increased by an average of 1.9+/-4.4% since the beginning of the HD treatment in group B. The body mass index (BMI) was lower in group A (19.3 +/- 2.3 vs 21.4 +/- 2.8 kg/m(2); P = 0.05). The arm-muscle circumference (AMC), the arm-muscle area (AMA), and triceps skinfold (TSF) were lower in group A than in group B. The fat mass assessed with anthropometry (10.8 +/- 4.0 vs 14.8 +/- 4.2 kg) was significantly lower in group A. The deviation of actual BW from ideal BW (IBW) was significantly lower in group A than in group B (80.6 +/- 10.7% vs 89.6 +/- 9.0%; P = 0.028); The deviations of actual BW, TSF, and AMA from standard values of the NHANES II study were more marked in group A than in group B. On the other hand, daily energy and protein intakes (DEI and DPI) were identical in both groups and met the recommendations for dialysis patients when normalized to the actual BW. When normalized to the IBW, the DEI appeared low. Energy expenditure was not different between groups, and not different from the resting metabolism calculated from the Harris and Benedict formula. Average albumin, prealbumin, and IgF-1 were normal and not different between groups. Branched-chain amino acids (BCAA), and especially leucine, were correlated with BMI in group A but not in group B. Serum total and free carnitine were low in both groups. Three patients had ascorbic acid deficiency in group A but none in group B. CONCLUSIONS: Hence, despite adequate dialysis dose and protein intake, patients treated with HD for a long period of time became malnourished, whereas the classical nutritional markers remained in normal ranges. Among the potential causes leading to malnutrition, inadequate energy intake and micronutrient deficiencies were found in these patients. PMID- 11208997 TI - Low-potassium and glucose-free dialysis maintains urea but enhances potassium removal. AB - BACKGROUND: The influence of potassium (K) removal on dialysis efficiency as measured by urea elimination is not clear. In this prospective, randomized, cross over study we investigated the magnitude of K removal and its effect on urea (u) elimination during high-flux haemodialysis (HD). METHODS: Twelve stable, non diabetic HD patients were investigated during three one-week standardized HD periods (1.8 m(2) high-flux polysulphone dialyser, treatment time 240 min, Qb = 300 ml/min, Qd = 500 ml/min, dialysate without glucose, bicarbonate 40 mmol/l), using dialysates containing 0 (0K), 1 (1K), and 2 (2K) mmol/l of K. Mass removal of K (M(K)) and u (M(U)) were measured during the mid-week treatment by partial dialysate collection. Urea reduction rate (URR) and Kt/V were determined. RESULTS: 0K, 1K and 2K treatments were perfectly comparable. Plasma K (PK) continuously declined reaching stable concentrations after 180 min. While 0K dialysate removed 117.1 mmol, 80.2 and 63.3 mmol (P < 0.001) were removed by 1K and 2K baths respectively. M(U) was not influenced by M(K) (r = 0.22) and amounted to 491.1 (0K), 508.6 (1K), and 506.2 (2K) mmol (NS) respectively. Accordingly, urea clearance, URR and Kt/V were constant during 0K, 1K and 2K treatments. CONCLUSIONS: Potassium-free dialysate significantly enhances potassium elimination. Potassium removal has no influence on urea elimination. High potassium removal, when needed, does not impair dialysis efficiency as measured by urea kinetics in high-flux, glucose-free, 40 mmol/l bicarbonate HD. PMID- 11208998 TI - Erythrocyte calcium influx is related to severity of ventricular arrhythmias in uraemic patients. AB - BACKGROUND: Myocardial disorders are a remarkable cause of morbidity and mortality in chronic haemodialysed patients (HD). They could be favoured by alteration of cell Ca(2+) handling. In previous studies we characterized an erythrocyte Ca(2+) influx, sensitive to membrane potential and inhibited by Ca(2+) antagonists. Since its maximal influx rate was decreased in HD patients, this study investigates if Ca(2+) influx alterations are related to myocardial disorders in HD patients. METHODS: Voltage-sensitive erythrocyte Ca(2+) influx was measured in 30 healthy controls and in 53 patients (47 HD patients and six patients with left ventricular hypertrophy and normal kidney function), using fura 2. In 29 HD patients and in six healthy subjects Ca(2+) influx was also determined in the presence of parathyroid hormone (PTH) in vitro. Patients were classified according to Lown's ventricular arrhythmias classification after 24-h Holter electrocardiograph (ECG) monitoring. Forty-six patients underwent echocardiography. RESULTS: Voltage-sensitive erythrocyte Ca(2+) influx was significantly reduced in HD patients. Maximal influx rate was significantly higher in HD patients of Lown's classes 3 and 4 (0.789 +/- 0.156 nmol/s, n = 8; P < 0.01) than in patients of classes 1 and 2 (0.499 +/- 0.055 nmol/s, n=15), or without ventricular arrhythmias (0.400 +/- 0.041 nmol/s, n = 24). Maximal influx rate was directly correlated to left ventricular mass index (LVM) (r = 0.353, P < 0.05). Subjects with left ventricular hypertrophy and normal kidney function displayed erythrocyte Ca(2+) influx similar to that of normal subjects. Multiple regression indicates that LVM and Ca(2+) influx were independently related to severity of arrhythmias. When added to the influx assay, PTH increased the maximal influx rate only in patients with ventricular arrhythmias. CONCLUSION: Myocardial dysfunction and altered ventricular excitability could be related in uraemic HD patients to alterations of calcium transport, as found in the erythrocyte model. Reduced resistance to PTH could contribute to this phenomenon. PMID- 11208999 TI - Assessment of total body water from anthropometry-based equations using bioelectrical impedance as reference in Korean adult control and haemodialysis subjects. AB - BACKGROUND: Several indirect prediction equations to estimate total body water (TBW) with simple demographic and anthropometric data are commonly used by researchers and dialysis units. These equations are largely based on observations in subjects of the Western hemisphere. The purpose of this study was to investigate the possible application of anthropometry-based TBW equations to a Korean adult control population and maintenance haemodialysis (HD) patients using multifrequency bioelectrical impedance analysis (BIA) as reference. METHODS: We performed BIA and anthropometric measurements in 67 healthy adults and 101 HD patients. Four anthropometry-based equations were used: 58% of actual body weight (TBW-58), the Watson formula (TBW-W), the Hume formula (TBW-H), and the Chertow formula (TBW-C). Multifrequency BIA was performed at fasting state in controls and after HD. RESULTS: TBW-BIA was 34.6+/-6.9 l in control and 29.9+/-5.1 l in HD patients. TBW-58 and TBW-C gave significantly greater TBWs than TBW-BIA in both control and HD subjects. The correlation coefficients of TBW-BIA with calculated TBWs were lowest in TBW-58 (0.754 in control and 0.856 in HD subjects), and highest in TBW-C (0.944 in control and 0.916 in HD subjects). Mean prediction error was greatest in the Chertow formula for control and HD patients. Mean prediction error, limits of agreement, and root mean square error were lowest between TBW-BIA and TBW-H in control and between TBW-BIA and TBW-W in HD subjects. The correlation coefficient in the Bland-Altman plot was closer to zero and parallel with TBW-W than TBW-H in control and HD subjects. CONCLUSION: Currently available TBW equations overestimate TBW in both Korean normal control subjects and HD patients. Among them, the Watson formula appears to be the closest to TBW and to have the least bias. Based on this analysis, it is reasonable to use the Watson formula for the calculation of TBW in Korean adult control and HD subjects until an Asian-based TBW equation is available. PMID- 11209000 TI - Ultrasound guided puncture of the brachial artery for haemodialysis fistula angiography. AB - BACKGROUND: Arterio-venous (a-v) fistulae of haemodialysis patients frequently require function assessment by angiography. The purpose of the present study was to determine the efficacy and safety of ultrasound-guided transbrachial catheterization when a-v fistulae were evaluated. METHODS: Between July 1996 and December 1997, 208 dialysis patients, whose a-v fistulae (arterial inflow < 50 ml/min or venous pressure > 150 mm Hg in three consecutive HD sessions) were at the wrist or elbow, underwent transbrachial angiography using an ultrasound guided 20-gauge IA needle to evaluate fistula function. Procedure-related symptoms or complications were noted in 28 patients and these were analysed. RESULTS: No apparent cases of vessel spasm or thrombosis were noted. Reported symptoms in 28 patients (13.5%) included local arm pain (3.3%), transient paresthesia (0.9%), mild ecchymosis (10.6%) and haematoma (0.9%). All complications were minor and none required surgical intervention. CONCLUSION: Ultrasound-guided puncture of the brachial artery is a safe, reliable and effective procedure in skilled hands and should be the preferred means of catheterization whenever haemodialysis angiography is performed. PMID- 11209001 TI - Effects of methionine loading on plasma and erythrocyte sulphur amino acids and sulph-hydryls before and after co-factor supplementation in haemodialysis patients. AB - BACKGROUND: Hyperhomocysteinaemia, which is potentially atherogenic, is common in chronic haemodialysis (HD) patients but the reason for this is not yet known. The methionine (Met) loading test (MLT) is used to test the capacity of homocysteine (Hcy) disposal by the trans-sulphuration pathway and thus may provide information on the metabolism of sulphur amino acids. The availability of vitamin B(6) and folic acid, as co-factors for Hcy metabolism may affect the response to MLT. In the present study, we compared the effect of Met loading on plasma and erythrocyte (RBC) sulphur amino acids and sulph-hydryls before and after co factor supplementation in healthy subjects and HD patients. METHODS: In 10 HD patients and 10 healthy subjects the effect of Met loading, 0.1 g/kg BW, on plasma and RBC methionine metabolites was studied over 7 h, before and after 4 weeks supplementation with high daily doses of vitamin B(6) (200 mg) and folic acid (15 mg). RESULTS: MLT before vitamin supplementation in HD patients, compared to the healthy subjects, caused significantly greater increases in plasma Hcy levels (43+/-12 vs 15+/-5 micromol/l), cysteinesulphinic acid (CSA) (1.34 vs 0.36 micromol/l) and gamma-glutamylcysteine (0.98+/-0.83 vs -01+/-0.42 micromol/l) and no decline in plasma cysteine (Cys) (0.5+/-33.9 vs -31+/-26 micromol/l), but no significant differences in plasma taurine, cysteinylglycine, and glutathione concentrations. In RBCs there was a small increase in Hcy levels and a more marked increase in Tau levels, with no difference between the healthy subjects and HD patients. Vitamin supplementation in pharmacological doses failed to correct the abnormal responses to MLT in the HD patients. CONCLUSIONS: Oral methionine loading in HD patients leads to higher accumulation of Hcy and other Met metabolites in plasma and RBCs than in healthy subjects, indicating impaired metabolism of sulphur amino acids via the trans-sulphuration pathway. Supplementation with high doses of vitamin B(6) and folic acid does not correct this impairment, suggesting that it most probably is not due to lack of these co factors. PMID- 11209002 TI - Adequacy of dialysis reduces the doses of recombinant erythropoietin independently from the use of biocompatible membranes in haemodialysis patients. AB - BACKGROUND: The effect of the adequacy of dialysis on the response to recombinant human erythropoietin (rHuEpo) therapy is still incompletely understood because of many confounding factors such as iron deficiency, biocompatibility of dialysis membranes, and dialysis modality that can interfere. METHODS: We investigated the relationship between Kt/V and the weekly dose of rHuEpo in 68 stable haemodialysis (HD) patients (age 65+/-15 years) treated with bicarbonate HD and unsubstituted cellulose membranes for 6-343 months (median 67 months). Inclusion criteria were HD for at least 6 months, subcutaneous rHuEpo for at least 4 months, transferrin saturation (TSAT) > or = 20%, serum ferritin > or = 100 ng/ml, and haematocrit (Hct) level targeted to 35% for at least 3 months. Exclusion criteria included HBsAg and HIV positivity, need for blood transfusions or evidence of blood loss in the 3 months before the study, and acute or chronic infections. Hct and haemoglobin (Hb) levels were evaluated weekly for 4 weeks; TSAT, serum ferritin, Kt/V, PCRn, serum albumin (sAlb), and weekly dose of rHuEpo were evaluated at the end of observation. No change in dialysis or therapy prescription was made during the study. RESULTS: The results for the whole group of patients were: Hct 35 +/- 1.2%, Hb 12.1 +/- 0.6 g/dl, TSAT 29 +/- 10%, serum ferritin 204 +/- 98 ng/ml, sAlb 4.1 +/- 0.3 g/dl, Kt/V 1.33 +/-0.19, PCRn 1.11+/- 0.28 g/kg/day, weekly dose of rHuEpo 123 +/- 76 U/kg. Hct did not correlate with Kt/V, whereas rHuEpo dose and Kt/V were inversely correlated (r = -0.49; P < 0.0001). Multiple regression analysis with rHuEpo as dependent variable confirmed Kt/V as the only significant variable (P < 0.002). Division of the patients into two groups according to Kt/V (group A, Kt/V < or = 1.2; group B, Kt/V > or = 1.4), showed no differences in Hct levels between the two groups, while weekly rHuEpo dose was significantly lower in group B than in group A (group B, 86 +/- 33 U/kg; group A, 183 +/- 95 U/kg, P < 0.0001). CONCLUSIONS: In iron-replete HD patients treated with rHuEpo in the maintenance phase, Kt/V exerts a significant sparing effect on rHuEpo requirement independent of the use of biocompatible synthetic membranes. By optimizing rHuEpo responsiveness, an adequate dialysis treatment can contribute to the reduction of the costs of rHuEpo therapy. PMID- 11209003 TI - Intravenous iron for CAPD populations: proactive or reactive strategies? AB - BACKGROUND: The European best practice guideline [Nephrol Dial Transplant 1999; 14 (Suppl 5)] (5A) for the management of anaemia suggests that > 85% of the CAPD population should have a haemoglobin level of > 11.0 g/dl. METHODS: We developed and implemented an outpatient-based protocol for intravenous iron sucrose (IV Fe) and erythropoietin (Epo) in CAPD patients showing iron deficiency despite oral iron therapy. We managed a total of 103 patients over 13 months of study. All CAPD patients were included, regardless of co-morbidity. Treatment developed in two phases: in phase 1 (reactive) (months 1-8), patients with markers of iron deficiency (ferritin < 100 ng/ml or ferritin 100-500 and percentage hypochromic red cells (%HRC) > or =5) were converted from oral iron to IV Fe (300 mg) and reviewed after 4-8 weeks according to haemoglobin (Hb). In phase 2 (proactive) (months 9-13), the criteria for iron therapy were extended: ferritin < 150 ng/ml or ferritin 150-500 and %HRC > or = 2. Patients then received IV Fe (200 mg) and were reviewed after 4 weeks according to Hb. RESULTS: The median haemoglobin increased from 11.0 (Inter quartile range, IQR, 10.1-12.6) g/dl to 11.7 (11.0 12.7) g/dl (P = 0.06). The proportion of patients with absolute iron deficiency (ferritin < 100 ng/ml) decreased from 24 to 2%. The percentage of hypochromic red cells (%HRC) decreased from 4 (2-7) to 1 (1-4) (P < 0.01). CONCLUSIONS: An integrated Epo and IV Fe policy increased the number of patients reaching the European guideline from 50 to 75% with no increase in the population median Epo requirements (42 (IQR, 25-95) IU/kg/week vs 45 (27-101) (P = NS)). This study demonstrates the benefit of early (proactive) intervention in achieving population compliance within current guidelines for renal anaemia. PMID- 11209004 TI - Contrast-enhanced ultrasound voiding cystography as a screening examination for vesicoureteral reflux in the follow-up of renal transplant recipients: a new approach. AB - BACKGROUND: The aim of the study was to evaluate a new diagnostic procedure, ultrasound contrast-enhanced voiding cystography (USVC), for vesicoureteral reflux (VUR) in renal transplant recipients and to compare it with radionuclide voiding cystography (RVC). METHODS: Twenty-three renal transplant recipients with recurrent urinary tract infection were investigated simultaneously by RVC and USVC. After catheterization, the empty bladder was filled with normal saline (mean 250+/-30 ml) and 30-45 mBq of (99m)Tc-labelled colloid. At the end of filling the bladder, 19.5 ml of galactose-based, microbubble-containing echo enhancing agent, at a concentration of 200 mg/ml, was instilled. During the filling and voiding phases the movement of the radiotracer was recorded by a gamma camera and the presence of microbubbles in the urinary tract by ultrasound. RVC was used to detect and grade the degree of VUR. RESULTS: Nuclear studies identified VUR in 16 (69.6%) of 23 recipients with recurrent urinary tract infection: VUR grade I in three (13%) recipients, grade II in eight (34.8%) and grade III in five (21.7%) using a simplified grading system. USVC with contrast enhancement detected VUR in 14 (60.9%) recipients. Overall sensitivity and specificity of contrast-enhanced USVC was 75 and 71%, respectively. Statistical analysis showed that the accuracy of this procedure increased with higher grades of VUR and its sensitivity reached 100% for detection of VUR grade III. CONCLUSION: In our preliminary study, contrast-enhanced USVC has proved to be an effective examination, with the same accuracy rate as RVC in detecting grade III VUR episodes with low diagnostic accuracy for low reflux grades. PMID- 11209005 TI - Renal allograft rupture is associated with rejection or acute tubular necrosis, but not with renal vein thrombosis. AB - BACKGROUND: Whereas rejection was reported to be the most common cause of renal allograft rupture (RAR) in the pre-cyclosporin era, renal vein thrombosis (RVT) is purported to be the main cause of RAR in patients taking cyclosporin. The extremely low incidence of RVT in our series (0.11%) prompted us to analyse our collective with regard to RAR. METHOD: Between 1974 and 1999, 1811 renal transplants were performed. Patients with RAR, defined as a tear of the renal capsule and parenchyma, were identified and possible underlying factors studied. RESULTS: RAR was diagnosed in nine male and five female recipients (0.8%) with a median age of 36 years. Immunosuppression consisted of azathioprine and prednisolone in seven patients and of cyclosporin-based therapy in the seven others. At exploration five grafts were removed immediately: three because of irreversible rejection, one because of deep wound infection, and one with a twisted renal vein. Six of the nine salvaged kidneys have been functioning after a mean observation time of 45 months. In the pre-cyclosporin era RAR was associated with acute rejection in five out of seven cases as compared with only three of the seven on cyclosporin treatment. Core biopsies might have been the cause in three cases. CONCLUSION: RAR is a rare complication after renal transplantation. Acute rejection still represents the most frequent cause of RAR in the cyclosporin era. PMID- 11209006 TI - Outcome of renal replacement therapy in the very elderly. AB - BACKGROUND: In a retrospective case-note and computer database analysis we assessed the outcome of very elderly patients (> or = 75 years old) with end stage renal disease (ESRD) on renal replacement therapy (RRT). METHODS: Fifty eight individuals aged 75 or over (group 1) commenced RRT between 1 January 1991 and 31 December 1995. Comparisons were made with other patients commencing RRT who were divided into two groups: group 2 (201 individuals 65-74 years old) and group 3 (379 patients <65 years old). All subjects were followed up until the point of assessment (30 June 1998), the time of death, or withdrawal from dialysis. Survival rates in the three groups were compared using Kaplan-Meier method. The number of hospital admissions, length of in-patient stay, and complications rate on RRT were assessed for group 1. RESULTS: One-year survival rates in groups 1, 2 and 3 were 53.5, 72.6, and 90.6% respectively and the 5-year survival rates were 2.4, 18.8, and 61.4% respectively. The very elderly spent 20% of their time in hospital, 46% had two co-morbid factors at the outset, and 26% developed multiple complications while on RRT. Withdrawal from dialysis remained the most common cause of death in this group of individuals (38%), followed by cardiovascular causes (24%) and infections (22%). CONCLUSION: Very elderly ESRD patients on RRT have a very poor outcome and, since they are the largest growing group of RRT patients, this has important implications for future health policies. PMID- 11209007 TI - Increase of physical activity level after successful renal transplantation: a 5 year follow-up study. AB - BACKGROUND: Physical activity (PA) level of end-stage renal disease (ESRD) patients after renal transplantation (TP) is a largely unexplored field, although it is an important component of quality of life. METHODS: Using the Baecke self administered and the Five-City Project 7-day PA recall questionnaires, PA level was estimated in 32 consecutive ESRD patients (12 males, 20 females; mean age 45.9+/-13.1 years; mean dialysis duration 23.5+/-21.8 months) admitted for renal TP and to whom no exercise programme of any kind was proposed. PA were recorded 1, 3, 6, 12 and 60 months after TP. RESULTS: Immediate pre-TP PA level of renal transplant candidates was between 18 and 35% less than that of age-matched healthy subjects (P < 0.05), depending on gender and questionnaire. After an immediate decrease in PA level 1 month post-TP, mean PA level increased and reached a plateau 1 year after TP. This gain in PA capacity reached 30%, as compared with pre-TP values (P = 0.06 to P < 0.01). During the fifth year after TP, the mean level of PA was unchanged. A more qualitative analysis, allowed by the sub-score comparisons, showed that although the occupational status of the patients remained the same, they participated significantly more in moderate and even high intensity PA (leisure, sports, household chores) after TP. CONCLUSIONS: Most renal graft recipients are spontaneously more active after TP, an observation consistent with a better quality of life. Therefore, they should be advised precisely about how to resume more strenuous activities such as sports in order to avoid cardiac or musculoskeletal disorders in relation to their weakened pre-TP condition. PMID- 11209008 TI - Efficacy and drug interactions of the new HMG-CoA reductase inhibitors cerivastatin and atorvastatin in CsA-treated renal transplant recipients. AB - BACKGROUND: Hyperlipidaemia is an important risk factor for cardiovascular disease in renal transplant recipients. The aim of this study was to test the efficacy and possible drug-drug interactions of the new HMG-CoA reductase inhibitors (statins) atorvastatin and cerivastatin in cyclosporin A (CsA)-treated renal transplant patients. Subjects and methods. Thirty patients with stable graft function and LDL cholesterol of 130 mg/dl were randomly assigned to active treatment groups (10 mg atorvastatin or 0.2 mg cerivastatin), or a control group. CsA blood trough levels were controlled on a weekly basis and adapted if they changed more than 25% from baseline values (100-150 ng/ml). Lipid levels and routine laboratory parameters before and after a treatment period of 3 months were compared. RESULTS: In the group treated with cerivastatin no significant changes in CsA blood trough levels occurred (CsA 116+/-21 ng/ml vs 110+/-20 ng/ml). In contrast, in the group treated with atorvastatin, four of 10 patients had a rise in CsA blood trough levels of more than 25% within 7-14 days of starting therapy. In the remaining patients no significant changes in CsA drug levels occurred. After therapy with atorvastatin or cerivastatin, total cholesterol, LDL cholesterol, and triglycerides were significantly lower compared with baseline conditions. No changes of CsA or lipoprotein levels were present in the control group. CONCLUSION: In our study population both statins were very effective in lowering elevated LDL cholesterol levels. Cerivastatin did not influence CsA blood trough levels, whereas atorvastatin increased CsA levels in four of 10 patients. Further research in a larger study is necessary in order to confirm these results and to investigate the possible reasons for this drug interaction. PMID- 11209010 TI - Intravascular ultrasound imaging before and after angioplasty for stenosis of arteriovenous fistulae in haemodialysis patients. AB - BACKGROUND: Complications of haemodialysis vascular access have emerged as a major cause of patient morbidity. Intravascular ultrasound imaging is a new technical modality providing visualization of the vessel lumen and wall structure in a cross-sectional fashion. Percutaneous transluminal angioplasty has long been used in the treatment of stenoses of arteriovenous fistulae. However, there is no detailed quantitative information on the stenotic lesion and the morphological change by angioplasty. METHODS: Intravascular ultrasound studies were performed in 40 haemodialysis patients with 63 stenoses in arteriovenous fistulae who had percutaneous transluminal angioplasty. The patients were qualitatively and quantitatively evaluated for echogenic patterns and morphological changes before and after angioplasty. RESULTS: Morphological plaque features in stenotic lesions were classified as 37 soft (58%), five hard (8%), 20 mixed (32%), and one calcified sites. Plaque fractures after angioplasty were detected in 45/63 (71%) instances. The lumen cross-sectional area was found to be dilated approximately threefold (from 3.8+/-2.4 to 11.1+/-4.5 mm(2)) and the external elastic membrane cross-sectional area was dilated approximately twofold (from 11.1+/-5.3 to 19.8+/ 8.1 mm(2)) after angioplasty. CONCLUSION: These results indicate that intravascular ultrasound allows both qualitative and quantitative assessments of arteriovenous fistulae in haemodialysis patients. The results further suggest that the mechanism of expansion of arteriovenous fistulae stenoses by percutaneous transluminal angioplasty involves stretching of the vessel wall as well as plaque fractures. PMID- 11209009 TI - Altered antioxidant defence in a mouse adriamycin model of glomerulosclerosis. AB - BACKGROUND: Antioxidant enzyme status changes in experimental models of chronic renal disease with glomerulosclerosis. Most of the studies are performed in rats. We now investigate whether a mouse model with more rapid development of glomerulosclerosis is suitable for the study of radical-associated renal disease. METHODS: Female BALB/c mice are injected intravenously with a single dose of adriamycin (10 mg/kg). The development of glomerular and interstitial injury is evaluated by means of renal function parameters and histology. Renal cortex activities of catalase, Cu/Zn and Mn superoxide dismutase and glutathione peroxidase are measured by enzymatic techniques, and their mRNA levels by Northern blot analysis. RESULTS: The mice develop proteinuria and hypercholesterolaemia; glomerulosclerosis is present 20 days after adriamycin injection. Involvement of reactive oxygen intermediates in the disease process is supported by an increased cortex level of glutathione (1.77+/-0.13 vs 1.31+/-0.12 micromol/g kidney; P = 0.021) and ferric iron deposition in the tubulointerstitial compartment. Glomerulosclerosis and tubulointerstitial lesions are accompanied by decreased cortex activities of catalase (0.19+/-0.01 vs 0.23+/ 0.01 U/mg protein; P = 0.024), glutathione peroxidase (0.28+/-0.01 vs 0.32+/-0.01 U/mg protein; P = 0.049) and Mn superoxide dismutase (6.61+/-0.91 vs 9.25+/-0.99 U/mg protein, P = 0.020). We find decreased cortex mRNA levels only for glutathione peroxidase. CONCLUSION: The fast development of glomerulosclerosis combined with an altered antioxidant status makes this mouse adriamycin model a suitable alternative for the slower rat models. PMID- 11209011 TI - Spontaneous remission of HCV-induced cryoglobulinaemic glomerulonephritis. PMID- 11209012 TI - Laparoscopic renal denervation for intractable ADPKD-related pain. PMID- 11209013 TI - Desmopressin may be hazardous in thrombotic microangiopathy. PMID- 11209014 TI - End-stage renal disease in a bodybuilder: a multifactorial process or simply doping? PMID- 11209015 TI - Three cases of sequential liver-kidney transplantation from living-related donors. PMID- 11209016 TI - Vomiting, hyperkalaemia and cardiac rhythm disturbances. PMID- 11209017 TI - Parathyroidectomy in a hypercalcaemic patient with inappropriately normal plasma parathyroid hormone: an unusual way to arrive at the correct diagnosis. PMID- 11209018 TI - The haemodialysis patient with night sweats, ascites, and increased CA 125. PMID- 11209021 TI - Cyclo-oxygenase-2 and renal function. PMID- 11209023 TI - STOPPING at the CAPPP of good HOPE. PMID- 11209024 TI - A polymorphism in the gene for the endothelial nitric oxide synthase and diabetic nephropathy. PMID- 11209025 TI - Necrotizing glomerulonephritis associated with Hodgkin's disease. PMID- 11209026 TI - Tumour lysis syndrome in a patient with metastatic melanoma treated with biochemotherapy. PMID- 11209027 TI - Tranexamic-acid-induced acute renal cortical necrosis in a patient with haemophilia A. PMID- 11209028 TI - Acetaminophen toxicity induced non-oliguric acute tubular necrosis. PMID- 11209029 TI - Continuous rifampicin administration inducing acute renal failure. PMID- 11209030 TI - Response to recombinant human erythropoietin (rHu-Epo) in a patient with chronic renal failure and myelomonocytic leukaemia. PMID- 11209031 TI - Pharmacokinetic of nevirapine in haemodialysis. PMID- 11209033 TI - Successful treatment of digoxin intoxication by haemoperfusion with specific columns for beta2-microgloblin-adsorption (Lixelle) in a maintenance haemodialysis patient. PMID- 11209032 TI - Safety of interferon and ribavirin therapy in haemodialysis patients with chronic hepatitis C: results of a pilot study. PMID- 11209034 TI - Looking for new sources of organ donations. PMID- 11209035 TI - Epstein-Barr virus encephalitis in a renal allograft recipient diagnosed by polymerase chain reaction on cerebrospinal fluid and successfully treated with ganciclovir. PMID- 11209037 TI - PubMed Central: The GenBank of the published literature. PMID- 11209038 TI - Looking for the exit: How do malaria parasites escape from red blood cells? PMID- 11209039 TI - The six functions of Agrobacterium VirE2. PMID- 11209040 TI - Biomolecular processes in the fast lane. PMID- 11209041 TI - Ancient DNA and the origin of modern humans. PMID- 11209042 TI - Cancer epigenetics takes center stage. PMID- 11209043 TI - Lactic acid: New roles in a new millennium. PMID- 11209044 TI - Can mosaic tumor vessels facilitate molecular diagnosis of cancer? PMID- 11209045 TI - Transmitochondrial mice: proof of principle and promises. PMID- 11209046 TI - A molecular logic gate. AB - We propose a scheme for molecule-based information processing by combining well studied spectroscopic techniques and recent results from chemical dynamics. Specifically it is discussed how optical transitions in single molecules can be used to rapidly perform classical (Boolean) logical operations. In the proposed way, a restricted number of states in a single molecule can act as a logical gate equivalent to at least two switches. It is argued that the four-level scheme can also be used to produce gain, because it allows an inversion, and not only a switching ability. The proposed scheme is quantum mechanical in that it takes advantage of the discrete nature of the energy levels but, we here discuss the temporal evolution, with the use of the populations only. On a longer time range we suggest that the same scheme could be extended to perform quantum logic, and a tentative suggestion, based on an available experiment, is discussed. We believe that the pumping can provide a partial proof of principle, although this and similar experiments were not interpreted thus far in our terms. PMID- 11209047 TI - The role of rigidity in DNA looping-unlooping by AraC. AB - We applied two experiments useful in the study of ligand-regulated DNA binding proteins to AraC, the dimeric regulator of the Escherichia coli l-arabinose operon. In the absence of arabinose, AraC prefers to loop DNA by binding to two half-sites that are separated by 210 base pairs, and in the presence of arabinose it prefers to bind to adjacently located half-sites. The basis for this ligand regulated shift in binding appears to result from a shift in the rigidity of the system, where rigidity both in AraC protein in the absence of arabinose, and in the DNA are required to generate the free energy differences that produce the binding preferences. Eliminating the dimerization domains and connecting the two DNA binding domains of AraC by a flexible peptide linker should provide a protein whose behavior mimics that of AraC when there is no interaction between its dimerization and DNA binding domains. The resulting protein bound to adjacent half-sites on the DNA, like AraC protein in the presence of arabinose. When the two double-stranded DNA half-sites were connected by 24 bases of single-stranded, flexible DNA, wild-type AraC protein bound to the DNA in the presence and absence of arabinose with equal affinity, showing that AraC modulates its DNA binding affinity in response to arabinose by shifting the relative positions of its DNA binding domains. These results are consistent with the light switch mechanism for the action of AraC, refine the model, and extend the range of experimental tests to which it has been subjected. PMID- 11209049 TI - The "glycogen shunt" in exercising muscle: A role for glycogen in muscle energetics and fatigue. AB - Stimulated by recent (13)C and (31)P NMR studies of exercising muscle, we propose a model of the energetics of contraction. Previous studies of energetics have followed energy consumption. However, the rapidity of contraction, in 10-40 msec, requires that energy be delivered rapidly, so that the muscle has power requirements of rapid energy expenditure that are ultimately met by the slower averaged consumption of carbon and oxygen from blood. We propose that energy is supplied in milliseconds by glycogenolysis and that between contractions, glycogenesis refills the pools. The energy for glycogenesis is supplied by oxidative phosphorylation. This mechanism utilizes the rapid conversion of glycogen phosphorylase, the "fight-or-flight" enzyme, to its active form. Lactate is necessarily generated by this pathway to serve as a time buffer between fast and slow energy needs, which resolves the paradoxical generation of lactate in well oxygenated tissue. Consequences of the glycogen shunt are compatible with numerous biochemical and physiological experiments. The model provides a possible mechanism for muscle fatigue, suggesting that at low but nonzero glycogen concentrations, there is not enough glycogen to supply millisecond energy needs. PMID- 11209048 TI - A complex signaling module governs the activity of MalT, the prototype of an emerging transactivator family. AB - MalT, the specific activator of the maltose regulon, is the prototype of a family of high-molecular-mass ATP-binding bacterial transcription activators. On binding of its two positive effectors, the inducer maltotriose and ATP, MalT oligomerizes to an active state competent for promoter binding and transcription activation. In addition to its previously known DNA-binding domain, limited proteolysis showed that MalT contains three other domains, the boundaries of which were accurately delimited by N-terminal microsequencing. The N-terminal domain alone binds ATP. Maltotriose binding involves an extended region corresponding to domains 2 and 3, although weak binding to domain 3 alone was also observed. Moreover, maltotriose binding induces a conformational shift involving a movement of both domains 1 and 3 with respect to domain 2, leading to the active form of the protein. Sequence examination of the MalT homologues suggests that these three domains might constitute a signaling module. PMID- 11209050 TI - Refined crystal structure of DsRed, a red fluorescent protein from coral, at 2.0 A resolution. AB - The crystal structure of DsRed, a red fluorescent protein from a corallimorpharian, has been determined at 2.0-A resolution by multiple-wavelength anomalous dispersion and crystallographic refinement. Crystals of the selenomethionine-substituted protein have space group P2(1) and contain a tetramer with 222 noncrystallographic symmetry in the asymmetric unit. The refined model has satisfactory stereochemistry and a final crystallographic R factor of 0.162. The protein, which forms an obligatory tetramer in solution and in the crystal, is a squat rectangular prism comprising four protomers whose fold is extremely similar to that of the Aequorea victoria green fluorescent protein despite low ( approximately 23%) amino acid sequence homology. The monomer consists of an 11-stranded beta barrel with a coaxial helix. The chromophores, formed from the primary sequence -Gln-Tyr-Gly- (residues 66-68), are arranged in a approximately 27 x 34-A rectangular array in two approximately antiparallel pairs. The geometry at the alpha carbon of Gln-66 (refined without stereochemical restraints) is consistent with an sp(2) hybridized center, in accord with the proposal that red fluorescence is because of an additional oxidation step that forms an acylimine extension to the chromophore [Gross, L. A., Baird, G. S., Hoffman, R. C., Baldridge, K. K. & Tsien, R. Y. (2000) Proc. Natl. Acad. Sci. USA 87, 11990-11995]. The carbonyl oxygen of Phe-65 is almost 90 degrees out of the plane of the chromophore, consistent with theoretical calculations suggesting that this is the minimum energy conformation of this moiety despite the conjugation of this group with the rest of the chromophore. PMID- 11209051 TI - Simultaneous observation of the O---O and Fe---O2 stretching modes in oxyhemoglobins. AB - Understanding of the chemical nature of the dioxygen moiety of oxyhemoglobin is crucial for elucidation of its physiological function. In the present work, direct Raman spectroscopic observation of both the FeO(2) and OO stretching modes unambiguously establishes the vibrational characteristics of the oxygen-bound heme moiety in the hemoglobins of Chlamydomonas eugametos and Synechocystis PCC6803. In addition to providing the resonance Raman assignment of the OO stretching mode (1136 cm(-1) for Chlamydomonas, 1133 cm(-1) for Synechocystis) in an oxyhemoglobin with an iron-porphyrin, this study also reports unusually low frequencies for the FeO(2) stretching modes (554 cm(-1)). The effect of strong hydrogen bonding to the bound oxygen is confirmed by changes in the frequency of the FeO(2) stretching mode on mutation of distal residues. These findings suggest an enzymatic function rather than an oxygen transport role for these hemoglobins. PMID- 11209052 TI - A family of tissue-specific resistin-like molecules. AB - We have identified a family of resistin-like molecules (RELMs) in rodents and humans. Resistin is a hormone produced by fat cells. RELMalpha is a secreted protein that has a restricted tissue distribution with highest levels in adipose tissue. Another family member, RELMbeta, is a secreted protein expressed only in the gastrointestinal tract, particularly the colon, in both mouse and human. RELMbeta gene expression is highest in proliferative epithelial cells and is markedly increased in tumors, suggesting a role in intestinal proliferation. Resistin and the RELMs share a cysteine composition and other signature features. Thus, the RELMs together with resistin comprise a class of tissue-specific signaling molecules. PMID- 11209053 TI - Mitochondrial DNA sequences in ancient Australians: Implications for modern human origins. AB - DNA from ancient human remains provides perspectives on the origin of our species and the relationship between molecular and morphological variation. We report analysis of mtDNA from the remains of 10 ancient Australians. These include the morphologically gracile Lake Mungo 3 [ approximately 60 thousand years (ka) before present] and three other gracile individuals from Holocene deposits at Willandra Lakes (<10 ka), all within the skeletal range of living Australians, and six Pleistocene/early Holocene individuals (15 to <8 ka) from Kow Swamp with robust morphologies outside the skeletal range of contemporary indigenous Australians. Lake Mungo 3 is the oldest (Pleistocene) "anatomically modern" human from whom DNA has been recovered. His mtDNA belonged to a lineage that only survives as a segment inserted into chromosome 11 of the nuclear genome, which is now widespread among human populations. This lineage probably diverged before the most recent common ancestor of contemporary human mitochondrial genomes. This timing of divergence implies that the deepest known mtDNA lineage from an anatomically modern human occurred in Australia; analysis restricted to living humans places the deepest branches in East Africa. The other ancient Australian individuals we examined have mtDNA sequences descended from the most recent common ancestor of living humans. Our results indicate that anatomically modern humans were present in Australia before the complete fixation of the mtDNA lineage now found in all living people. Sequences from additional ancient humans may further challenge current concepts of modern human origins. PMID- 11209054 TI - Function-structure analysis of proteins using covarion-based evolutionary approaches: Elongation factors. AB - The divergent evolution of protein sequences from genomic databases can be analyzed by the use of different mathematical models. The most common treat all sites in a protein sequence as equally variable. More sophisticated models acknowledge the fact that purifying selection generally tolerates variable amounts of amino acid replacement at different positions in a protein sequence. In their "stationary" versions, such models assume that the replacement rate at individual positions remains constant throughout evolutionary history. "Nonstationary" covarion versions, however, allow the replacement rate at a position to vary in different branches of the evolutionary tree. Recently, statistical methods have been developed that highlight this type of variation in replacement rates. Here, we show how positions that have variable rates of divergence in different regions of a tree ("covarion behavior"), coupled with analyses of experimental three-dimensional structures, can provide experimentally testable hypotheses that relate individual amino acid residues to specific functional differences in those branches. We illustrate this in the elongation factor family of proteins as a paradigm for applications of this type of analysis in functional genomics generally. PMID- 11209055 TI - Attractin/mahogany/zitter plays a critical role in myelination of the central nervous system. AB - The rat zitter (zi) mutation induces hypomyelination and vacuolation in the central nervous system (CNS), which result in early-onset tremor and progressive flaccid paresis. By positional cloning, we found a marked decrease in Attractin (Atrn) mRNA in the brain of the zi/zi rat and identified zi as an 8-bp deletion at a splice donor site of Atrn. Atrn has been known to play multiple roles in regulating physiological processes that are involved in monocyte-T cell interaction, agouti-related hair pigmentation, and control of energy homeostasis. Rat Atrn gene encoded two isoforms, a secreted and a membrane form, as a result of alternative splicing. The zi mutation at the Atrn locus darkened coat color when introduced into agouti rats, as also described in mahogany (mg) mice, carrying the homozygous mutation at the Atrn locus. Transgenic rescue experiments showed that the membrane-type Atrn complemented both neurological alteration and abnormal pigmentation in zi/zi rats, but that the secreted-type Atrn complemented neither mutant phenotype. Furthermore, we discovered that mg mice exhibited hypomyelination and vacuolation in the CNS associated with body tremor. We conclude from these results that the membrane Atrn has a critical role in normal myelination in the CNS and would provide insights into the physiology of myelination as well as the etiology of myelin diseases. PMID- 11209056 TI - CpG island protects Rous sarcoma virus-derived vectors integrated into nonpermissive cells from DNA methylation and transcriptional suppression. AB - CpG islands are important in the protection of adjacent housekeeping genes from de novo DNA methylation and for keeping them in a transcriptionally active state. However, little is known about their capacity to protect heterologous genes and assure position-independent transcription of adjacent transgenes or retroviral vectors. To tackle this question, we have used the mouse aprt CpG island to flank a Rous sarcoma virus (RSV)-derived reporter vector and followed the transcriptional activity of integrated vectors. RSV is an avian retrovirus which does not replicate in mammalian cells because of several blocks at all levels of the replication cycle. Here we show that our RSV-derived reporter proviruses linked to the mouse aprt gene CpG island remain undermethylated and keep their transcriptional activity after stable transfection into both avian and nonpermissive mammalian cells. This effect is most likely caused by the protection from de novo methylation provided by the CpG island and not by enhancement of the promoter strength. Our results are consistent with previous finding of CpG islands in proximity to active but not inactive proviruses and support further investigation of the protection of the gene transfer vectors from DNA methylation. PMID- 11209058 TI - A fibronectin fragment inhibits tumor growth, angiogenesis, and metastasis. AB - We have shown previously that a polymeric form of fibronectin is strongly antimetastatic when administered systemically to tumor-bearing mice. The polymeric fibronectin, sFN, is formed in vitro by treating soluble fibronectin with a 76-aa peptide, III1-C, which is derived from the first type III repeat in fibronectin. Here we show that the III1-C peptide and sFN also reduce tumor growth in mice, and that this effect correlates with a low density of blood vessels in the tumors of the treated mice. III1-C also polymerized fibrinogen, and the fibrinogen polymer, sFBG, had antitumor and antiangiogenic effects similar to those of sFN. Mice that had been injected s.c. with three different types of human tumor cells and treated with biweekly i.p. injections of III1-C, sFN, or sFBG over a 5-week period had tumors that were 50-90% smaller than those of control mice. Blood vessel density in the tumors of the treated mice was reduced by 60-80% at the end of the experiment. Xenograft tumors from a human breast carcinoma line (MDA-MB-435) were particularly susceptible to these treatments. Metastasis into the lungs from the primary s.c. tumors also was inhibited in the mice treated with III1-C and the two polymers. The III1-C peptide is an antiangiogenic and antimetastatic agent. Because of its ability to suppress tumor growth, angiogenesis, and metastasis, we have named the III1-C peptide anastellin [from anastello (Greek), inhibit, force a retreat]. PMID- 11209057 TI - Soluble CD14 enriched in colostrum and milk induces B cell growth and differentiation. AB - Induction of resting B cell growth and differentiation requires a complex series of temporally coordinated signals that are initiated on contact with activated helper T cells. These signals complement one another, each rendering the B cell susceptible to factors supporting progressive activation. Here, we demonstrate that soluble CD14 (sCD14) bypasses the physiological sequelae of events that limit B cell activation. B cell growth and differentiation in vitro is induced by both native and recombinant forms of sCD14 at nanomolar concentrations. sCD14 mediated cellular activation does not require membrane CD14 expression, depends on a region of CD14 that is not involved in lipopolysaccharide binding, and requires functional Toll-like receptor 4. Consistent with biological activity of sCD14 in vitro, its administration to neonatal mice enhances Ig secretion. The results presented establish sCD14 as a naturally occurring soluble B cell mitogen of mammalian origin. PMID- 11209059 TI - Point mutations in the murine fumarylacetoacetate hydrolase gene: Animal models for the human genetic disorder hereditary tyrosinemia type 1. AB - Hereditary tyrosinemia type 1 (HT1) is a severe autosomal recessive metabolic disease associated with point mutations in the human fumarylacetoacetate hydrolase (FAH) gene that disrupt tyrosine catabolism. An acute form of HT1 results in death during the first months of life because of hepatic failure, whereas a chronic form leads to gradual development of liver disease often accompanied by renal dysfunction, childhood rickets, neurological crisis, and hepatocellular carcinoma. Mice homozygous for certain chromosome 7 deletions of the albino Tyr; c locus that also include Fah die perinatally as a result of liver dysfunction and exhibit a complex syndrome characterized by structural abnormalities and alterations in gene expression in the liver and kidney. Here we report that two independent, postnatally lethal mutations induced by N-ethyl-N nitrosourea and mapped near Tyr are alleles of Fah. The Fah(6287SB) allele is a missense mutation in exon 6, and Fah(5961SB) is a splice mutation causing loss of exon 7, a subsequent frameshift in the resulting mRNA, and a severe reduction of Fah mRNA levels. Increased levels of the diagnostic metabolite succinylacetone in the urine of the Fah(6287SB) and Fah(5961SB) mutants indicate that these mutations cause a decrease in Fah enzymatic activity. Thus, the neonatal phenotype present in both mutants is due to a deficiency in Fah caused by a point mutation, and we propose Fah(5961SB) and Fah(6287SB) as mouse models for acute and chronic forms of human HT1, respectively. PMID- 11209060 TI - Conditional immortalization of freshly isolated human mammary fibroblasts and endothelial cells. AB - Reports differ as to whether reconstitution of telomerase activity alone is sufficient for immortalization of different types of human somatic cells or whether additional activities encoded by other "immortalizing" genes are also required. Here we show that ectopic expression of either the catalytic subunit of human telomerase (hTERT) or a temperature-sensitive mutant (U19tsA58) of simian virus 40 large-tumor antigen alone was not sufficient for immortalization of freshly isolated normal adult human mammary fibroblasts and endothelial cells. However, a combination of both genes resulted in the efficient generation of immortal cell lines irrespective of the order in which they were introduced or whether they were introduced early or late in the normal proliferative lifespan of the cultures. The order and timing of transduction, however, did influence genomic stability. Karyotype analysis indicated that introduction of both transgenes at early passage, with hTERT first, yielded diploid cell lines. Temperature-shift experiments revealed that maintenance of the immortalized state depended on continued expression of functional U19tsA58 large-tumor antigen, with hTERT alone unable to maintain growth at nonpermissive temperatures for U19tsA58 large-tumor antigen. Such conditional diploid lines may provide a useful resource for both cell engineering and for studies on immortalization and in vitro transformation. PMID- 11209061 TI - The evolutionary history of chromosomal super-integrons provides an ancestry for multiresistant integrons. AB - Integrons are genetic elements that acquire and exchange exogenous DNA, known as gene cassettes, by a site-specific recombination mechanism. Characterized gene cassettes consist of a target recombination sequence (attC site) usually associated with a single open reading frame coding for an antibiotic resistance determinant. The affiliation of multiresistant integrons (MRIs), which contain various combinations of antibiotic resistance gene cassettes, with transferable elements underlies the rapid evolution of multidrug resistance among diverse Gram negative bacteria. Yet the origin of MRIs remains unknown. Recently, a chromosomal super-integron (SI) harboring hundreds of cassettes was identified in the Vibrio cholerae genome. Here, we demonstrate that the activity of its associated integrase is identical to that of the MRI integrase, IntI1. We have also identified equivalent integron superstructures in nine distinct genera throughout the gamma-proteobacterial radiation. Phylogenetic analysis revealed that the evolutionary history of the system paralleled that of the radiation, indicating that integrons are ancient structures. The attC sites of the 63 antibiotic-resistance gene cassettes identified thus far in MRIs are highly variable. Strikingly, one-fifth of these were virtually identical to the highly related yet species-specific attC sites of the SIs described here. Furthermore, antimicrobial resistance homologues were identified among the thousands of genes entrapped by these SIs. Because the gene cassettes of SIs are substrates for MRIs, these data identify SIs as the source of contemporary MRIs and their cassettes. However, our demonstration of the metabolic functions, beyond antibiotic resistance and virulence, of three distinct SI gene cassettes indicates that integrons function as a general gene-capture system for bacterial innovation. PMID- 11209062 TI - Bunyamwera bunyavirus nonstructural protein NSs is a nonessential gene product that contributes to viral pathogenesis. AB - Bunyamwera virus (family Bunyaviridae, genus Bunyavirus) contains a tripartite negative-sense RNA genome. The smallest RNA segment, S, encodes the nucleocapsid protein N and a nonstructural protein, NSs, in overlapping reading frames. We have generated a mutant virus lacking NSs, called BUNdelNSs, by reverse genetics. Compared with the wild-type (wt) virus, BUNdelNSs exhibited a smaller plaque size and generated titers of virus approximately 1 log lower. In mammalian cells, the mutant expressed greatly increased levels of N protein; significantly, the marked inhibition of host cell protein synthesis shown by wt virus was considerably impaired by BUNdelNSs. When inoculated by the intracerebral route BUNdelNSs killed BALB/c mice with a slower time course than wt and exhibited a reduced cell to-cell spread, and titers of virus in the brain were lower. In addition, the abrogation of NSs expression changed Bunyamwera virus from a noninducer to an inducer of an interferon-beta promoter. These results suggest that, although not essential for growth in tissue culture or in mice, the bunyavirus NSs protein has several functions in the virus life cycle and contributes to viral pathogenesis. PMID- 11209063 TI - Antigenic and genetic heterogeneity of Borrelia burgdorferi populations transmitted by ticks. AB - The genome of Borrelia burgdorferi encodes a large number of lipoproteins, many of which are expressed only at certain stages of the spirochete's life cycle. In the current study we describe the B. burgdorferi population structure with respect to the production of two lipoproteins [outer surface protein A (OspA) and outer surface protein C (OspC)] during transmission from the tick vector to the mammalian host. Before the blood meal, the bacteria in the tick were a homogeneous population that mainly produced OspA only. During the blood meal, the population became more heterogeneous; many bacteria produced both OspA and OspC, whereas others produced only a single Osp and a few produced neither Osp. From the heterogeneous spirochetal population in the gut, a subset depleted of OspA entered the salivary glands and stably infected the host at time points >53 hr into the blood meal. We also examined genetic heterogeneity at the B. burgdorferi vlsE locus before and during the blood meal. In unfed ticks, the vlsE locus was stable and one predominant and two minor alleles were detected. During the blood meal, multiple vlsE alleles were observed in the tick. Tick feeding may increase recombination at the vlsE locus or selectively amplify rare vlsE alleles present in unfed ticks. On the basis of our data we propose a model, which is different from the established model for B. burgdorferi transmission. Implicit in our model is the concept that tick transmission converts a homogeneous spirochete population into a heterogeneous population that is poised to infect the mammalian host. PMID- 11209064 TI - A default mode of brain function. AB - A baseline or control state is fundamental to the understanding of most complex systems. Defining a baseline state in the human brain, arguably our most complex system, poses a particular challenge. Many suspect that left unconstrained, its activity will vary unpredictably. Despite this prediction we identify a baseline state of the normal adult human brain in terms of the brain oxygen extraction fraction or OEF. The OEF is defined as the ratio of oxygen used by the brain to oxygen delivered by flowing blood and is remarkably uniform in the awake but resting state (e.g., lying quietly with eyes closed). Local deviations in the OEF represent the physiological basis of signals of changes in neuronal activity obtained with functional MRI during a wide variety of human behaviors. We used quantitative metabolic and circulatory measurements from positron-emission tomography to obtain the OEF regionally throughout the brain. Areas of activation were conspicuous by their absence. All significant deviations from the mean hemisphere OEF were increases, signifying deactivations, and resided almost exclusively in the visual system. Defining the baseline state of an area in this manner attaches meaning to a group of areas that consistently exhibit decreases from this baseline, during a wide variety of goal-directed behaviors monitored with positron-emission tomography and functional MRI. These decreases suggest the existence of an organized, baseline default mode of brain function that is suspended during specific goal-directed behaviors. PMID- 11209065 TI - Emotion-induced changes in human medial prefrontal cortex: I. During cognitive task performance. AB - Regional cerebral blood flow (BF) was examined in regions of the medial prefrontal cortex (MPFC) with positron-emission tomography while subjects performed two cognitive tasks, reading nouns aloud and generating appropriate verbs for the same nouns. The control task was passive viewing of the same words. BF was reduced in regions of the MPFC during word reading and naive verb generation, relative to a control state in which the subjects passively viewed nouns. Practicing verb generation produced improved performance, as measured by response time, which was strongly correlated with further reductions in MPFC and hypothalamic BF. After practice, when verb generation was performed on a novel list of words, reaction times slowed and the pattern of MPFC BF reverted to that seen in the word reading and naive conditions. A separate behavioral study of the verb-generation task indicated that anxiety, high during naive use-generation as measured by heart rate and self-report, decreased with practice on the task but returned with the introduction of a novel list of words. Taken together, these results suggest that the MPFC is part of a network, including the hypothalamus and brainstem, whose activity reflects a dynamic interplay between cognitive task performance and emotion. PMID- 11209067 TI - Dynamic imaging of coherent sources: Studying neural interactions in the human brain. AB - Functional connectivity between cortical areas may appear as correlated time behavior of neural activity. It has been suggested that merging of separate features into a single percept ("binding") is associated with coherent gamma band activity across the cortical areas involved. Therefore, it would be of utmost interest to image cortico-cortical coherence in the working human brain. The frequency specificity and transient nature of these interactions requires time sensitive tools such as magneto- or electroencephalography (MEG/EEG). Coherence between signals of sensors covering different scalp areas is commonly taken as a measure of functional coupling. However, this approach provides vague information on the actual cortical areas involved, owing to the complex relation between the active brain areas and the sensor recordings. We propose a solution to the crucial issue of proceeding beyond the MEG sensor level to estimate coherences between cortical areas. Dynamic imaging of coherent sources (DICS) uses a spatial filter to localize coherent brain regions and provides the time courses of their activity. Reference points for the computation of neural coupling may be based on brain areas of maximum power or other physiologically meaningful information, or they may be estimated starting from sensor coherences. The performance of DICS is evaluated with simulated data and illustrated with recordings of spontaneous activity in a healthy subject and a parkinsonian patient. Methods for estimating functional connectivities between brain areas will facilitate characterization of cortical networks involved in sensory, motor, or cognitive tasks and will allow investigation of pathological connectivities in neurological disorders. PMID- 11209066 TI - Emotion-induced changes in human medial prefrontal cortex: II. During anticipatory anxiety. AB - Regional cerebral blood flow (BF) was examined in the human medial prefrontal cortex (MPFC) with positron emission tomography during anticipatory anxiety. Transient anxiety was induced in normal subjects by having them anticipate a painful shock to the fingers of one hand. BF was decreased during anticipatory anxiety, relative to an eyes-closed resting condition, in two regions of the MPFC (Brodmann Areas 10/32 and 24/25). BF decreases in these areas were inversely correlated with anxiety self rating, such that the least anxious subjects exhibited the largest BF reductions, whereas the most anxious subjects showed no significant BF reduction or a slight increase. BF changes in MPFC and in the midbrain were correlated with each other and with anxiety self rating. These results are consistent with the hypothesis that BF reductions in MPFC, previously observed in cognitive tasks, reflect a dynamic balance between focused attention and subject anxiety and may occur from a functionally active baseline or default state. The characterization of such relationships within the human brain enables new insights into the integration of cognition and emotion. PMID- 11209070 TI - Mechanism of ribosomal peptide bond formation. PMID- 11209068 TI - Estradiol rapidly inhibits soluble guanylyl cyclase expression in rat uterus. AB - Previous reports that investigated the regulation of the NO/soluble guanylyl cyclase (sGC)/cGMP pathway by estrogenic compounds have focused primarily on the levels of NO, NO-producing enzymes, and cGMP in various tissues. In this study, we demonstrate that 17beta-estradiol (E2) regulates the alpha(1) and beta(1) subunits of the NO receptor, sGC, at the mRNA and protein levels in rat uterus. Using real-time quantitative PCR, we found that within 1 h of in vivo E2 administration to rats, sGC mRNA levels begin to diminish. After 3 h, there is a maximal diminution of sGC mRNA expression (sGC alpha(1) 10% and sGC beta(1) 33% of untreated). This effect was blocked by the estrogen receptor antagonist, ICI 182,780, indicating that estrogen receptor is required. The effect of E2 also was observed in vitro with incubations of uterine tissue, indicating that the response does not depend on the secondary release of other hormones or factors from other tissues. Puromycin did not block the effect, suggesting the effects occur because of preexisting factors in uterine tissues and do not require new protein synthesis. Using immunoblot analysis, we found that sGC protein levels also were reduced by E2 over a similar time course as the sGC mRNA. We conclude that sGC plays a vital role in the NO/sGC/cGMP regulatory pathway during conditions of elevated estrogen levels in the rat uterus as a result of the reduction of sGC expression. PMID- 11209071 TI - Fluid control in multichannel structures by electrocapillary pressure. AB - We demonstrate control of fluid motion in three-dimensional structures with thousands of microchannels. Fluids are manipulated via an electrocapillary pressure, originating from electrostatic control of the solid/fluid interfacial tension in the microchannels. Reversible fluid displacement has been achieved for all channel orientations with respect to gravity. The velocities of several centimeters per second are nearly two orders of magnitude higher than the velocities demonstrated by other electrofluidic actuation principles. PMID- 11209069 TI - Activation of a mitogen-activated protein kinase pathway is involved in disease resistance in tobacco. AB - Hypersensitive response (HR), a form of programmed cell death, is frequently associated with plant disease resistance. It has been proposed that mitogen activated protein kinase (MAPK) cascades regulate HR cell death based on pharmacological studies by using kinase inhibitors. However, direct evidence is lacking. Here, we demonstrate that NtMEK2, a MAPK kinase, is upstream of salicylic acid-induced protein kinase (SIPK) and wounding-induced protein kinase (WIPK), two tobacco MAPKs that are activated by various pathogens or pathogen derived elicitors. Expression of a constitutively active mutant of NtMEK2 induces HR-like cell death in tobacco, which is preceded by the activation of endogenous SIPK and WIPK. In addition, NtMEK2-SIPK/WIPK cascade appears to control the expression of 3-hydroxy-3-methylglutaryl CoA reductase (HMGR) and l-phenylalanine ammonia lyase (PAL), two defense genes encoding key enzymes in the phytoalexin and salicylic acid biosynthesis pathways. These results demonstrate that a plant MAPK cascade controls multiple defense responses against pathogen invasion. PMID- 11209072 TI - Proximity-induced superconductivity in DNA. AB - Conductivity measurements on double-stranded DNA molecules deposited by a combing process across a submicron slit between rhenium/carbon metallic contacts reveal conduction to be ohmic between room temperature and 1 kelvin. The resistance per molecule is less than 100 kilohm and varies weakly with temperature. Below the superconducting transition temperature (1 kelvin) of the contacts, proximity induced superconductivity is observed. These results imply that DNA molecules can be conducting down to millikelvin temperature and that phase coherence is maintained over several hundred nanometers. PMID- 11209073 TI - Resonant electron scattering by defects in single-walled carbon nanotubes. AB - We report the characterization of defects in individual metallic single-walled carbon nanotubes by transport measurements and scanned gate microscopy. A sizable fraction of metallic nanotubes grown by chemical vapor deposition exhibits strongly gate voltage-dependent resistance at room temperature. Scanned gate measurements reveal that this behavior originates from resonant electron scattering by defects in the nanotube as the Fermi level is varied by the gate voltage. The reflection coefficient at the peak of a scattering resonance was determined to be about 0.5 at room temperature. An intratube quantum dot device formed by two defects is demonstrated by low-temperature transport measurements. PMID- 11209074 TI - A three-dimensional synthetic metallic crystal composed of single-component molecules. AB - Molecular metals normally require charge transfer between two different chemical species. We prepared crystals of [Ni(tmdt)2] (tmdt, trimethylenetetrathiafulvalenedithiolate) and carried out crystal structure analyses and resistivity measurements. The analyses and measurements revealed that these single-component molecular crystals are metallic from room temperature down to 0.6 kelvin. Ab initio molecular orbital calculations suggested that pi molecular orbitals form conduction bands. The compact molecular arrangement, intermolecular overlap integrals of the highest occupied and lowest unoccupied molecular orbitals, and tight-binding electronic band structure calculation revealed that [Ni(tmdt)2] is a three-dimensional synthetic metal composed of planar molecules. PMID- 11209075 TI - String tension and stability of magic tip-suspended nanowires. AB - Multishell helical gold nanowires were recently imaged by electron microscopy. We show theoretically that the contact with the gold tips at either end of the wire plays a crucial role and that local minima in the string tension rather than the total wire free energy determine the nanowire stability. Density functional electronic structure calculations of the simplest and thinnest coaxial gold and silver wires of variable radius and chirality were carried out. We found a string tension minimum for a single-tube gold nanowire that is chiral and consists of seven strands, in striking agreement with observation. In contrast, no such minimum was found for silver, where the s-d competition leading to surface reconstruction is lacking. PMID- 11209076 TI - Orbital forcing of the marine isotope stage 9 interglacial. AB - Milankovitch orbital forcing theory has been used to assign time scales to many paleoclimate records. However, the validity of this theory remains uncertain, and independent sea-level chronologies used to test its applicability have been restricted largely to the past approximately 135,000 years. Here, we report U series ages for coral reefs formed on Henderson Island during sea-level high stands occurring at approximately 630,000 and approximately 330,000 years ago. These data are consistent with the hypothesis that interglacial climates are forced by Northern Hemisphere summer solar insolation centered at 65 degrees N latitude, as predicted by Milankovitch theory. PMID- 11209077 TI - Modern human ancestry at the peripheries: a test of the replacement theory. AB - The replacement theory of modern human origins stipulates that populations outside of Africa were replaced by a new African species of modern humans. Here we test the replacement theory in two peripheral areas far from Africa by examining the ancestry of early modern Australians and Central Europeans. Analysis of pairwise differences was used to determine if dual ancestry in local archaic populations and earlier modern populations from the Levant and/or Africa could be rejected. The data imply that both have a dual ancestry. The diversity of recent humans cannot result exclusively from a single Late Pleistocene dispersal. PMID- 11209078 TI - Natal homing in a marine fish metapopulation. AB - Identifying natal origins of marine fishes is challenging because of difficulties in conducting mark-recapture studies in marine systems. We used natural geochemical signatures in otoliths (ear bones) to determine natal sources in weakfish (Cynoscion regalis), an estuarine-spawning marine fish, in eastern North America. Spawning site fidelity ranged from 60 to 81%, comparable to estimates of natal homing in birds and anadromous fishes. These data were in contrast to genetic analyses of population structure in weakfish. Our findings highlight the need for consideration of spatial processes in fisheries models and have implications for the design of marine reserves in coastal regions. PMID- 11209079 TI - Migration along orthodromic sun compass routes by arctic birds. AB - Flight directions of birds migrating at high geographic and magnetic latitudes can be used to test bird orientation by celestial or geomagnetic compass systems under polar conditions. Migration patterns of arctic shorebirds, revealed by tracking radar studies during an icebreaker expedition along the Northwest Passage in 1999, support predicted sun compass trajectories but cannot be reconciled with orientation along either geographic or magnetic loxodromes (rhumb lines). Sun compass routes are similar to orthodromes (great circle routes) at high latitudes, showing changing geographic courses as the birds traverse longitudes and their internal clock gets out of phase with local time. These routes bring the shorebirds from high arctic Canada to the east coast of North America, from which they make transoceanic flights to South America. The observations are also consistent with a migration link between Siberia and the Beaufort Sea region by way of sun compass routes across the Arctic Ocean. PMID- 11209080 TI - A ribonucleotide reductase homolog of cytomegalovirus and endothelial cell tropism. AB - Human cytomegalovirus infects vascular tissues and has been associated with atherogenesis and coronary restenosis. Although established laboratory strains of human cytomegalovirus have lost the ability to grow on vascular endothelial cells, laboratory strains of murine cytomegalovirus retain this ability. With the use of a forward-genetic procedure involving random transposon mutagenesis and rapid phenotypic screening, we identified a murine cytomegalovirus gene governing endothelial cell tropism. This gene, M45, shares sequence homology to ribonucleotide reductase genes. Endothelial cells infected with M45-mutant viruses rapidly undergo apoptosis, suggesting that a viral strategy to evade destruction by cellular apoptosis is indispensable for viral growth in endothelial cells. PMID- 11209081 TI - A role for flavin monooxygenase-like enzymes in auxin biosynthesis. AB - Although auxin is known to regulate many processes in plant development and has been studied for over a century, the mechanisms whereby plants produce it have remained elusive. Here we report the characterization of a dominant Arabidopsis mutant, yucca, which contains elevated levels of free auxin. YUCCA encodes a flavin monooxygenase-like enzyme and belongs to a family that includes at least nine other homologous Arabidopsis genes, a subset of which appears to have redundant functions. Results from tryptophan analog feeding experiments and biochemical assays indicate that YUCCA catalyzes hydroxylation of the amino group of tryptamine, a rate-limiting step in tryptophan-dependent auxin biosynthesis. PMID- 11209083 TI - Categorical representation of visual stimuli in the primate prefrontal cortex. AB - The ability to group stimuli into meaningful categories is a fundamental cognitive process. To explore its neural basis, we trained monkeys to categorize computer-generated stimuli as "cats" and "dogs." A morphing system was used to systematically vary stimulus shape and precisely define the category boundary. Neural activity in the lateral prefrontal cortex reflected the category of visual stimuli, even when a monkey was retrained with the stimuli assigned to new categories. PMID- 11209082 TI - Transgenic monkeys produced by retroviral gene transfer into mature oocytes. AB - Transgenic rhesus monkeys carrying the green fluorescent protein (GFP) gene were produced by injecting pseudotyped replication-defective retroviral vector into the perivitelline space of 224 mature rhesus oocytes, later fertilized by intracytoplasmic sperm injection. Of the three males born from 20 embryo transfers, one was transgenic when accessible tissues were assayed for transgene DNA and messenger RNA. All tissues that were studied from a fraternal set of twins, miscarried at 73 days, carried the transgene, as confirmed by Southern analyses, and the GFP transgene reporter was detected by both direct and indirect fluorescence imaging. PMID- 11209084 TI - Role of ER export signals in controlling surface potassium channel numbers. AB - Little is known about the identity of endoplasmic reticulum (ER) export signals and how they are used to regulate the number of proteins on the cell surface. Here, we describe two ER export signals that profoundly altered the steady-state distribution of potassium channels and were required for channel localization to the plasma membrane. When transferred to other potassium channels or a G protein coupled receptor, these ER export signals increased the number of functional proteins on the cell surface. Thus, ER export of membrane proteins is not necessarily limited by folding or assembly, but may be under the control of specific export signals. PMID- 11209085 TI - Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. AB - Dilated cardiomyopathy is a severe pathology of the heart with poorly understood etiology. Disruption of the gene encoding the negative immunoregulatory receptor PD-1 in BALB/c mice, but not in BALB/c RAG-2-/- mice, caused dilated cardiomyopathy with severely impaired contraction and sudden death by congestive heart failure. Affected hearts showed diffuse deposition of immunoglobulin G (IgG) on the surface of cardiomyocytes. All of the affected PD-1-/- mice exhibited high-titer circulating IgG autoantibodies reactive to a 33-kilodalton protein expressed specifically on the surface of cardiomyocytes. These results indicate that PD-1 may be an important factor contributing to the prevention of autoimmune diseases. PMID- 11209086 TI - New strategies in the treatment of acute myelogenous leukemia (AML): in vitro culture of aml cells--the present use in experimental studies and the possible importance for future therapeutic approaches. AB - In vitro studies of cultured native acute myelogenous leukemia (AML) blasts and cell lines have contributed significantly to our present knowledge about the pathogenesis of AML. In the present article we review different techniques for preparation and in vitro culture of AML blasts. Well-characterized serum-free in vitro conditions can now be used in experimental studies of AML, and this makes comparisons between different studies easier. We also describe assays for characterization of AML progenitor subsets (i.e., suspension cultures, colony assays, long-term in vitro culture, xenotransplantation in immunocompromised mice), and we discuss the possible use of AML cell lines as experimental models in AML. Furthermore, clinical studies suggest that the in vitro growth characteristics of AML blasts assayed by short-term culture of the total native populations can be used as a predictor of prognosis after intensive chemotherapy. These in vitro assays may therefore be used for more accurate identification of prognostic parameters and thereby form a basis for the development of simplified laboratory techniques suitable for routine evaluation of patients undergoing risk adapted therapy. However, it will be equally important to further evaluate the clinical relevance of assays for primitive AML progenitors, and to develop simplified methods that can be used to characterize these progenitor subsets in the routine clinical evaluation. PMID- 11209087 TI - Gene transfer into nonhuman primate hematopoietic stem cells: implications for gene therapy. AB - Hematopoietic stem cells (HSCs) are desirable targets for gene therapy because of their self-renewal and multilineage differentiation abilities. Retroviral vectors are extensively used for HSC gene therapy. However, the initial human trials of HSC gene marking and therapy showed that the gene transfer efficiency into human HSCs with retroviral vectors was very low in contrast to the much higher efficiency observed in murine experiments. The more quiescent nature of human HSCs and the lower density of retroviral receptors on them hindered the efficient gene transfer with retroviral vectors. Since nonhuman primates have marked similarity to humans in all aspects including the HSC biology, their models are considered to be important to evaluate and improve gene transfer into human HSCs. Using these models, clinically relevant levels (around 10% or even more) of gene modified cells in peripheral blood have recently been achieved after gene transfer into HSCs and their autologous transplantation. This has been made possible by improving ex vivo transduction conditions such as introduction of Flt 3 ligand and specific fibronectin fragment (CH-296) into ex vivo culture during transduction, and the use of retroviral vectors pseudotyped with the gibbon ape leukemia virus or feline endogenous retrovirus envelope. Other strategies including the use of lentiviral vectors and in vivo selective expansion of gene modified cells with the drug resistance gene or selective amplifier gene (also designated the molecular growth switch) are now being tested to further increase the fraction of gene-modified cells using nonhuman primate models. In addition to the high gene transfer efficiency, high-level and long-term expression of transgenes in human HSCs and their progeny is also required for effective HSC gene therapy. For this purpose, other backbones of retroviral vectors such as the murine stem cell virus and cis-DNA elements, such as the ss-globin locus control region and the chromatin insulator, also need to be tested in nonhuman primate models. Nonhuman primate studies will continue to provide an important framework for human HSC gene therapy. Well-designed nonhuman primate studies will also offer unique insights into the HSCs, immune system, and transplantation biology characteristic of large animals. PMID- 11209088 TI - Anti-VEGFR-2 scFvs for cell isolation. Single-chain antibodies recognizing the human vascular endothelial growth factor receptor-2 (VEGFR-2/flk-1) on the surface of primary endothelial cells and preselected CD34+ cells from cord blood. AB - Five specific single-chain antibodies recognizing the human vascular endothelial growth factor receptor-2 (VEGFR-2/KDR) were selected from a V-gene phage display library constructed from mice immunized with the extracellular domain of VEGFR-2 (Ig-like domain 1-7). All five scFv antibodies (A2, A7, B11, G3, and H1) bound to the purified native antigen in enzyme-linked immunosorbent assay and Dot Blot, and showed no crossreactivity to the human VEGF-receptor 1 (VEGFR-1). The selected antibodies recognize a conformation-dependent epitope of the native receptor and do not recognize denatured antigen in Western blots, as well as linear overlapping peptides comprising the sequence of the human VEGFR-2. The five scFv antibodies bind to the surface of endothelial cells overexpressing human VEGFR-2 c-DNA (PAE/VEGFR-2 cells) as detected by surface immunofluorescence using confocal microscopy. In addition scFv A7 specifically detected VEGFR-2 expressing endothelial cells in the glomerulus of frozen human kidney tissue sections. Therefore, A7 has potential clinical application as a marker for angiogenesis in cryosections of different human tissues. Additionally, two recombinant scFvs (A2 and A7) very efficiently recognize VEGFR-2 on PAE/VEGFR-2 cells and freshly prepared human umbilical vein endothelial cells by fluorescence activated cell sorter (FACS) analysis. The scFv fragment A7, which was the most sensitive antibody in FACS analysis, recognizes human CD34+VEGFR-2+ hematopoietic immature cells within the population of enriched CD34+ cells isolated from human cord blood. The dissociation constant of A7 was determined to be K(d) = 3.8 x 10( 9) M by BIAcore analysis. In conclusion, scFv fragment A7 seems to be an important tool for FACS analysis and cell sorting of vascular endothelial cells, progenitor cells and hematopoitic stem cells, which are positive for VEGFR-2 gene expression. PMID- 11209089 TI - Plasma levels of SDF-1 and expression of SDF-1 receptor on CD34+ cells in mobilized peripheral blood of non-Hodgkin's lymphoma patients. AB - CXCR4 is the receptor for the chemokine stromal derived factor-1 (SDF-1), is expressed on CD34+ cells, and has been implicated in the process of CD34+ cell migration and homing. We studied the mobilization of CD34/CXCR4 cells and the plasma levels of SDF-1 and flt3-ligand (flt3-L) in 36 non-Hodgkin's lymphoma patients receiving cyclophosphamide (Cy) plus G-CSF (arm A), Cy plus GM-CSF (arm B), or Cy plus GM-CSF followed by G-CSF (arm C) for peripheral blood stem cell (PBSC) mobilization and autotransplantation. We observed lower plasma levels of SDF-1 in PBSCs compared to premobilization bone marrow samples. The mean plasma SDF-1 levels were similar in PBSC collections in the three arms of the study. In contrast, SDF-1 levels in the apheresis collections of the "good mobilizers" (patients who collected a minimum of 2 x 10(6) CD34+ cells/kg in one to four PBSC collections) were significantly lower than the apheresis collections of the "poor mobilizers" (> or = 0.4 x 10(6) CD34+ cells/kg in the first two PBSC collections; 288 +/- 82 pg/ml versus 583 +/- 217 pg/ml; p = 0.0009). The mean percentage of CD34+ cells expressing CXCR4 in the apheresis collections was decreased in the PBSC collections compared with premobilization values from 28% to 19.4%. Furthermore, the percentage of CD34+ cells expressing CXCR4 in the good mobilizers was significantly lower compared with the poor mobilizers (14.7 +/- 2.1% versus 33.6 +/- 2.1%; p = 0.002). The good mobilizers had also significantly lower levels of flt3-L compared with the poor mobilizers (34 +/- 4 pg/ml versus 106 +/- 11 pg/ml; p = 0.006), Finally, the levels of flt3-L strongly correlated with SDF-1 levels (r = 0.8; p < 0.0001). We conclude: A) low plasma levels of SDF 1 and low expression of CXCR4 characterize patients with good mobilization outcome, and B) the levels of SDF-1 correlate with flt3-L, suggesting an association of these cytokines in mobilization of CD34+ cells. PMID- 11209090 TI - Major histocompatibility complex restriction between hematopoietic stem cells and stromal cells in vitro. AB - We have previously found that a significant number of hematopoietic progenitors accumulate in engrafted bones with the same major histocompatibility complex (MHC) as the transplanted bone marrow cells. In the present study, to further clarify the MHC restriction between hematopoietic stem cells (HSC) and microenvironment, we carried out cobblestone colony formation assays by culturing HSCs with MHC-matched or -mismatched stromal cell monolayers. The formation of cobblestone colonies under MHC-mismatched stromal cells significantly decreased in comparison with MHC-matched stromal cells. However, the decrease in cobblestone colony formation under MHC-mismatched stromal cells was not significant when using MHC class I-deficient HSC or stromal cells. Taken together with the results using B10 congenic strains, it is suggested that the MHC preference is restricted by MHC class Ia molecules. Treatment with monoclonal antibodies (mAbs) against MHC class Ia molecules of stromal cell phenotypes significantly enhanced the cobblestone colony formation, whereas treatment with mAbs against HSC phenotypes significantly inhibited it. The expression of cytokines to promote hematopoiesis was enhanced by the mAbs against stromal cell phenotypes. The enhancement of cytokine expression was also observed when stromal cells and HSCs were MHC-matched. These results suggest that signaling via the MHC molecules augments stromal cell activity and elicits the MHC restriction. PMID- 11209091 TI - Steel factor sustains SCL expression and the survival of purified CD34+ bone marrow cells in the absence of detectable cell differentiation. AB - CD34+ cells express the basic helix-loop-helix transcription factor SCL, which is essential for blood cell formation in vivo. In addition, their survival is critically dependent on hemopoietic growth factors. We therefore compared the effects of Steel factor (SF) and GM-CSF on the survival, proliferation, and differentiation of primary human CD34+ cells, as well as the role of SCL during these processes. GM-CSF suppresses apoptosis in CD34+ cells, which proliferate and differentiate into mature granulocytic and monocytic cells (CD34-CD13+) and loose SCL expression. In contrast, SF suppresses apoptosis without a significant increase in cell numbers, and the cells remain CD34+ and SCL+ with a blast-like morphology. Examination of apoptosis by the terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) reaction and of the cell cycle status indicated that SF is both a survival factor and a mitogenic factor for CD34+ cells. There was, however, constant cell death in a fraction of the population, which could be rescued by GM-CSF. Co-addition of SF and GM-CSF prevents the downregulation of SCL observed in the presence of GM-CSF by itself, allows for prolonged survival and expansion of CD34+ cells in culture, inhibits monocytic differentiation and impairs granulocytic differentiation. Finally, exposure to an antisense SCL but not a control oligonucleotide decreases SCL protein levels and prevents the suppression of apoptosis by SF without affecting GM-CSF-dependent cell survival. These observations suggest that the hemopoietic transcription factor SCL regulates the survival of CD34+ cells in response to SF. PMID- 11209092 TI - dlk inhibits stem cell factor-induced colony formation of murine hematopoietic progenitors: Hes-1-independent effect. AB - Delta-like (dlk) is a family of transmembrane proteins containing epidermal growth factor-like repeat motifs homologous to the notch/delta/serrate family. Recent studies suggest that dlk is a negative regulator of adipocyte differentiation, a promoting factor of cobblestone area colony formation, and a molecule which influences stromal cell-pre-B cell interactions and augments cellularity of developing thymocytes. However, the role of dlk in regulating the growth and differentiation of hematopoietic progenitors remains unclear. In the present study, we examined the effect of dlk on the proliferation of murine hematopoietic progenitors by hematopoietic growth factors. Soluble dlk-IgG Fc chimeric protein completely inhibited the colony formation of lineage-marker negative (Lin-) bone marrow cells by GM-CSF, G-CSF, or macrophage-CSF (M-CSF) in the presence of stem cell factor (SCF). However, dlk failed to inhibit the colony formation of Lin- bone marrow cells by CSF, as described above, or M-CSF plus interleukin 3. Furthermore, dlk failed to inhibit the colony formation of Hes-1 null fetal liver cells by M-CSF in the presence of SCF. These findings suggest that dlk is an important regulator of hematopoietic progenitor proliferation. Depending on the presence of SCF, dlk may act as a growth inhibitor, although dlk signaling does not mediate Hes-1 transcription factor. PMID- 11209093 TI - Immunogenicity of Ly5 (CD45)-antigens hampers long-term engraftment following minimal conditioning in a murine bone marrow transplantation model. AB - Various techniques are available for distinguishing donor from host cells evaluating the efficacy of conditioning regimen for experimental bone marrow transplantation (BMT). Techniques include the use of extracellular immunological markers, such as Ly5 (CD45), and intracellular biochemical markers, such as glucose-phosphate-isomerase (Gpi). Because Ly5 is an extracellular protein, the disparity between donor (Ly5.1) and host (Ly5.2) antigens may induce a weak immune response whereas with Gpi, no immune response is expected. This difference may be of particular concern in experimental transplantation approaches that use minimal conditioning such as low-dose total body irradiation (TBI). Such mild conditioning may not induce the immunosuppression required to overcome host rejection of Ly5 disparate cells. To compare the relative engraftment of Ly5.1 and Gpi-1(a) donor marrow, B6 (Gpi-1(b)/Ly5.2) mice were irradiated with low level TBI (0-6 Gy) and transplanted with several bone marrow (BM) doses (2 x 10(6)-5 x 10(7) cells). At 8, 26, and 52 weeks post-BMT, the level of donor engraftment was measured using flow cytometry (Ly5) or Gpi-electrophoresis. Lower engraftment levels were found in mice transplanted with Ly5 congenic BM in groups given low-dose TBI (< or = 4 Gy) and/or low doses of BM cells (BMC) (2 x 10(6)). However, when higher TBI or BMC doses were used, similar engraftment levels were found, suggesting sufficient immune suppression to allow equal engraftment of both sources of BM. These data suggest that even a minor phenotypic disparity between donor and host, such as Ly5, may necessitate high-dose TBI to prevent rejection. The combination of low-dose TBI or other nonmyeloablative conditioning strategies with small numbers of BMC may lead to reduced engraftment when extracellular immunological markers such as Ly5 are used for transplantation studies. Therefore, small immunological differences must be considered when using the Ly5 marker for engraftment. PMID- 11209094 TI - The cell cycle. PMID- 11209095 TI - The molecular perspective: the ribosome. PMID- 11209096 TI - Management of adult lower respiratory tract infection in primary care. PMID- 11209098 TI - Prospective study of the incidence, aetiology and outcome of adult lower respiratory tract illness in the community. AB - BACKGROUND: Acute lower respiratory tract illness in previously well adults is usually labelled as acute bronchitis and treated with antibiotics without establishing the aetiology. Viral infection is thought to be the cause in most cases. We have investigated the incidence, aetiology, and outcome of this condition. METHODS: Previously well adults from a stable suburban population consulting over one year with a lower respiratory tract illness were studied. For the first six months detailed investigations identified predetermined direct and indirect markers of infection. Evidence of infection was assessed in relation to presenting clinical features, indirect markers of infection, antibiotic use, and outcome. RESULTS: Consultations were very common, particularly in younger women (70/1000 per year in previously well women aged 16-39 years), mainly in the winter months; 638 patients consulted, of whom 316 were investigated. Pathogens were identified in 173 (55%) cases: bacteria in 82 (Streptococcus pneumoniae 54, Haemophilus influenzae 31, Moraxella catarrhalis 7), atypical organisms in 75 (Chlamydia pneumoniae 55, Mycoplasma pneumoniae 23), and viruses in 61 (influenza 23). Seventy nine (24%) had indirect evidence of infection. Bacterial and atypical infection correlated with changes in the chest radiograph and high levels of C reactive protein but not with (a) the GP's clinical assessment of whether infection was present, (b) clinical features other than focal chest signs, and (c) outcome, whether or not appropriate antibiotics were prescribed. CONCLUSIONS: Over 50% of patients have direct and/or indirect evidence of infection, most commonly bacterial and atypical pathogens, but the outcome is unrelated to the identified pathogens. Many patients improve without antibiotics and investigations do not help in the management of these patients. GPs can reassure patients of the causes and usual outcome of this self-limiting condition. PMID- 11209099 TI - Role of bronchoalveolar lavage in immunocompromised patients with pneumonia treated with a broad spectrum antibiotic and antifungal regimen. AB - BACKGROUND: In a retrospective study the value of bronchoalveolar lavage (BAL) in the diagnosis of pneumonia was investigated in 95 immunocompromised patients suffering from haematological disorders and receiving a regimen of broad spectrum antibiotics and antifungal agents (BSAR). METHODS: With the exception of four afebrile patients, all had fever, raised C reactive protein (CRP) levels, and new infiltrates visible on chest radiography. All patients underwent BAL to identify the organism causing the pneumonia and surveillance cultures were performed regularly for pathogens at different sites. Following classification of the isolates, patients with positive cultures were subdivided into two groups, pathogenic or contaminated. We investigated whether relevant pathogens were cultured only from the BAL fluid and whether they were susceptible to BSAR. RESULTS: Although 77 of the 95 patients were thrombocytopenic, bleeding during BAL occurred in only 15% of all patients. Ten days after the procedure the fever improved in 88% of patients, radiographic findings improved in 71%, and CRP levels improved in 75% of patients; 22% of patients died within 28 days. Pathologically relevant isolates were found in 65% of all patients. Respiratory pathogens were detected only in the BAL fluid of 29 of the 95 patients (35% Gram positive species, 40% Gram negative species, 11% Mycobacterium, 11% fungi, and 3% cytomegalovirus). In 16 of these 29 patients (55%) the pathogens cultured only from the BAL fluid were resistant to treatment. Pathogens detected only in the BAL fluid were not susceptible to a standard broad spectrum antibiotic and antifungal regimen including teicoplanin, ceftriaxon, tobramycin, and amphotericin B in 12 of the 29 patients (41%). CONCLUSIONS: Our data suggest that 12 patients were treated with broad spectrum antimicrobial agents which were not directed at the appropriate organism on in vitro sensitivity tests without BAL. BAL is a relatively safe procedure in the diagnosis of pneumonia, supplying important information in immunocompromised patients as well as in immunocompromised patients receiving BSAR. PMID- 11209097 TI - BTS guidelines: guidelines on the selection of patients with lung cancer for surgery. PMID- 11209100 TI - Leucocyte response and anti-inflammatory cytokines in community acquired pneumonia. AB - BACKGROUND: In the host defence of the lung neutrophils (PMN) play a central role. Apart from antimicrobial properties, recent data indicate that PMN also exert anti-inflammatory effects by stimulation and release of cytokine antagonists such as interleukin-1 receptor antagonist (IL-1ra). METHODS: Cytokine release from lipopolysaccharide stimulated whole blood was studied in 18 patients with community acquired pneumonia (CAP) and severe co-morbidities at admission and after 24 hours. Release of IL-1ra, interleukin-1beta (IL-1beta), tumour necrosis factor alpha (TNFalpha), soluble TNF receptor type I (sTNF-RI), and IL-8 was determined by ELISA. RESULTS: The mean (SD) leucocyte level at admission was 12.5 (4.1)/nl. There was a significant correlation between the release of anti inflammatory cytokines such as IL-1ra and sTNF-RI and the leucocyte count at admission and after 24 hours. Additional in vitro experiments showed that co incubation of peripheral blood mononuclear cells with autologous PMN led to a marked dose dependent increase in IL-1ra and sTNF-RI release. CONCLUSION: These results indicate that PMN may be responsible for the increase in anti inflammatory cytokines in CAP. Strategies to increase neutrophil counts may exert beneficial effects, not only by augmenting the antimicrobial activity but also by modulating the inflammatory cytokine response. PMID- 11209101 TI - Patient preferences for autonomy in decision making in asthma management. AB - BACKGROUND: Lower patient preferences for autonomy in management decision making during asthma exacerbations have been associated with an increased risk for future hospital admissions. We sought to examine patient preferences for asthma self-management autonomy, and the clinical and psychosocial factors associated with autonomy preferences. METHODS: A cross sectional observational study was performed with data collected between June 1995 and December 1997 of 212 adult patients with moderate to severe asthma managed, at least in part, at two teaching hospitals. Subjects completed a survey of autonomy preferences, quality of life, clinical morbidity and health service use, asthma knowledge, self efficacy, coping styles, and psychosocial measures. RESULTS: Patients preferred clinicians to assume the major role in most decision making about their management. However, patients wished to remain in control in choosing when to seek care and wanted to share decisions regarding initiating changes in medications during a moderate exacerbation. Multiple regression analysis showed that concerns about adverse effects of medications, education level, an active coping style, perceptions of the propensity of physicians to involve them in treatment decision making, and concerns about costs causing delays in seeking medical care were associated with preferences for autonomy in decision making. Autonomy preferences were not related to measures of concurrent clinical asthma control or health related quality of life. CONCLUSIONS: In a group of patients with moderate to severe asthma, a high proportion of whom were from socioeconomically disadvantaged backgrounds, education level, perceived physician behaviour, cost barriers to care, and psychosocial factors (but not clinical asthma control or management) were related to patient preferences for autonomy in management decision making during asthma exacerbations. This has implications for asthma action plans and design of self-management programmes. PMID- 11209103 TI - Patient weighting of importance of asthma symptoms. AB - BACKGROUND: Quality of life measures are increasingly important in evaluating outcomes in asthma. If some asthma symptoms are more troublesome to patients than others, this may affect their contribution to outcome measures. This study was designed to assess the relative importance of common symptoms in adults with asthma. METHODS: A postal survey using conjoint analysis was performed in 272 adults attending hospital outpatient clinics with moderately severe asthma. Patients were asked to chose between "symptom scenarios" offering different combinations of levels of five common asthma symptoms over one week. Two versions of the questionnaire were used with identical scenarios presenting symptoms in different orders. Different patients answered the two versions. Regression analysis was used to calculate symptom weights for daytime cough, breathlessness, wheeze and chest tightness, and sleep disturbance. RESULTS: Symptom order, percentage predicted peak expiratory flow (PEF), and symptoms in the week before the survey did not influence the choice of scenario. In both questionnaires patients were more likely to choose scenarios with low levels of cough and breathlessness than low sleep disturbance, wheeze or chest tightness. Regression weights for cough (-0.52) and breathlessness (-0.49) were twice those of wheeze ( 0.25), chest tightness (-0.27), and sleep disturbance (-0.25). For 12% of patients cough dominated patient preferences, regardless of all other symptoms. Age was inversely related to weight given by patients to breathlessness. CONCLUSIONS: The prominence of cough among other asthma symptoms was unexpected. Daytime cough and breathlessness had greater impact for patients than wheeze or sleep disturbance. Age influenced symptom burden, with younger patients giving greater weight to breathlessness than older patients. Conjoint analysis appears to be a useful method for establishing the relative importance of common symptoms. PMID- 11209102 TI - Association between obesity and asthma in 4-11 year old children in the UK. AB - BACKGROUND: There is evidence of a positive association between asthma and obesity in adults and in children. We investigated, in a large sample of English and Scottish primary school children, whether there is a consistent association between fatness and asthma symptoms in Britain. METHODS: A cross sectional analysis was made of 18 218 children aged 4-11 years who participated in the 1993 or 1994 surveys of the National Study of Health and Growth (NSHG). Children belonged either to English or Scottish representative samples, or an English inner city sample. Asthma attacks in the previous year, occasional wheeze, or persistent wheeze were the symptoms used in the analysis. Body mass index (BMI) and the sum of triceps and subscapular skinfolds converted to standard deviation scores (SDS) were used to assess levels of fatness. RESULTS: A total of 14 908 children (81.8%) were included in the analysis. In the multiple logistic analysis BMI and asthma (asthma attacks or wheeze) were associated in the representative sample (OR for the comparison of the 10th and 90th centiles of BMI 1.28, 95% CI 1.11 to 1.48), but sum of skinfolds was unrelated to asthma symptoms in most analyses. The association between asthma and BMI was stronger in girls than in boys in the inner city sample, but less convincingly in the representative sample. CONCLUSIONS: Levels of obesity are associated with asthma symptoms regardless of ethnicity. The association is more consistent for BMI than for sum of skinfolds, partly because obese children are more advanced in their maturation than other children. There is some evidence that, as in adults, the association is stronger in girls than in boys, but only in the multiethnic inner city sample. PMID- 11209104 TI - A randomised controlled trial of four weeks versus seven weeks of pulmonary rehabilitation in chronic obstructive pulmonary disease. AB - BACKGROUND: Pulmonary rehabilitation programmes have been shown to improve both exercise tolerance and health status in patients with chronic obstructive pulmonary disease (COPD). The optimal duration for a pulmonary rehabilitation programme is, however, unknown. To assess whether the current pulmonary rehabilitation programme could be shortened a randomised controlled trial was conducted in 44 patients with COPD who were allocated to either a seven week or a four week course. METHODS: Patients were randomised to either our standard seven week twice weekly outpatient based programme or a comparable but shortened four week course. They were assessed at baseline and at completion by the Chronic Respiratory Questionnaire (CRQ), the Breathing Problems Questionnaire (BPQ), the incremental shuttle walking test (SWT), and the treadmill endurance test (TET). RESULTS: Twenty one patients (61% men) of mean (SD) age 68 (9.2) years and forced expiratory volume in one second ( FEV(1)) 1.08 (0.4) l completed a conventional seven week course and 23 (67% men) of mean (SD) age 69 (8.8) years and FEV(1) 1.03 (0.3) l completed a shortened four week course. Patients who completed the seven week rehabilitation programme had greater improvements in all outcome measures than those undertaking the four week course. These differences reached clinical and statistical significance for the total CRQ score, which was the primary outcome variable (mean difference (95% confidence intervals (CI) of difference) -0.61(-0.15 to -1.08), p<0.05), and the CRQ domains of dyspnoea ( 0.80 (95% CI -0.13 to -1.48), p<0.05), emotion (-0.89 (95% CI -0.33 to -1.45), p<0.005), and mastery (-0.84 (95% CI -0.10 to -1.58), p<0.05). There were also trends towards greater improvements in exercise assessments in the seven week group but the differences did not reach statistical significance (SWT: mean difference -16.9 (95% CI 24.8 to -58.6), p=0.41; TET: geometric mean difference 1.21 (95% CI -0.60 to -2.47), p=0.56). CONCLUSIONS: A seven week course of pulmonary rehabilitation provides greater benefits to patients than a four week course in terms of improvements in health status. Larger prospective studies are required to determine the optimal duration of a pulmonary rehabilitation programme. PMID- 11209106 TI - Exhaled nitric oxide is reduced in infants with cystic fibrosis. AB - BACKGROUND: Exhaled nitric oxide levels are low in patients with cystic fibrosis (CF), despite the chronic inflammation present in the airways. This study aimed to determine whether levels of exhaled nitric oxide were reduced prior to the onset of respiratory symptoms in infants with CF. METHODS: The levels of exhaled nitric oxide were measured using a chemiluminescence analyser in five infants with CF and 11 healthy control subjects, both groups having a mean age of 48.6 days. RESULTS: Mean levels of exhaled nitric oxide were significantly lower in infants with CF than in the control group (4.9 ppb v 12.1 ppb; p=0.01). CONCLUSIONS: This finding may be the key to understanding the inflammatory processes in early cystic fibrosis and may lead to novel treatment approaches. PMID- 11209105 TI - The shuttle walking test: a reproducible method for evaluating the impact of shortness of breath on functional capacity in patients with advanced cancer. AB - BACKGROUND: Breathlessness leading to exercise limitation is common in patients with advanced cancer and is ineffectively treated. There are few research data to guide clinicians on best practice. The shuttle walking test has been validated for some conditions such as chronic obstructive pulmonary disease but not for advanced cancer. One of the well documented difficulties of doing clinical research in palliative care is the acceptability of assessment tests. This study examined the reproducibility of the shuttle walking test in patients with advanced cancer to help facilitate the systematic evaluation of interventions designed to improve breathlessness. METHODS: Patients performed three shuttle walks on separate days with continuous monitoring of arterial oxygen saturation and heart rate; simple pulmonary function (FEV(1)) was also recorded. Data on quality of life, anxiety, and depression were collected throughout the study period using appropriate questionnaires. Breathlessness was measured before and after exercise using a visual analogue scale. RESULTS: Data from 22 patients were compared between visits 2 and 3. There were no significant differences between the FEV(1) (1.89 v 1.90, p=0.73), distance walked on each test (245 m v 256 m, p=0.14), end-exercise levels of heart rate (107/min v 108/min, p=0.11), oxygen saturation (93.4% v 93.2%, p=0.38), or breathlessness scores (p=0.62) on the two occasions. Indices of quality of life, anxiety, and depression were also not different between the two tests. The investigation was very acceptable to patients, families, and staff. CONCLUSIONS: The shuttle walking test is a reproducible test of functional capacity in ambulant patients with advanced cancer, WHO performance status 1 or 2. The data indicate that a practice session is needed. It is easy to carry out and acceptable for patients with advanced cancer. PMID- 11209107 TI - Paediatric origins of adult lung disease. PMID- 11209108 TI - Transverse myelopathy and radiculomyelopathy associated with pulmonary atypical Mycobacterium infections. AB - Myelopathy is a well recognised but rare association with Mycobacterium tuberculosis infection, but has not been described with atypical mycobacteria. We report two cases of disabling myelopathy in association with pulmonary infection by Mycobacterium kansasii and Mycobacterium malmoense; the myelopathy is presumed to be a para-infectious phenomenon. PMID- 11209109 TI - Chronic venous insufficiency and venous leg ulceration. AB - Venous ulcers are the most common form of leg ulcers. Venous disease has a significant impact on quality of life and work productivity. In addition, the costs associated with the long-term care of these chronic wounds are substantial. Although the exact pathogenic steps leading from venous hypertension to venous ulceration remain unclear, several hypotheses have been developed to explain the development of venous ulceration. A better understanding of the current pathophysiology of venous ulceration has led to the development of new approaches in its management. New types of wound dressings, topical and systemic therapeutic agents, surgical modalities, bioengineered tissue, matrix materials, and growth factors are all novel therapeutic options that may be used in addition to the "gold standard," compression therapy, for venous ulcers. This review discusses current aspects of the epidemiology, pathophysiology, clinical presentation, diagnostic assessment, and current therapeutic options for chronic venous insufficiency and venous ulceration. (J Am Acad Dermatol 2001;44:401-21.) LEARNING OBJECTIVE: At the conclusion of this learning activity, participants should be familiar with the 3 main types of lower extremity ulcers and should improve their understanding of the epidemiology, pathogenesis, risk factors, clinical presentation, diagnostic assessment, and current therapies for chronic venous insufficiency and venous ulcers. PMID- 11209110 TI - Cutaneous photoprotection from ultraviolet injury by green tea polyphenols. AB - BACKGROUND: In animal models, extracts from green tea have been shown to be remarkably effective at reducing the severity of adverse human health effects of overexposure to ultraviolet (UV) radiation. Although sunscreens and other photoprotective measures have traditionally been used for this purpose, there is a need for additional measures and natural products are increasingly being explored for that purpose. OBJECTIVE: Our purpose was to evaluate the effect of polyphenols from green tea on parameters associated with acute UV injury. METHODS: Areas of skin of normal volunteers were treated with an extract of green tea or one of its constituents. Thirty minutes later, the treated sites were exposed to a 2 minimal erythema dose solar simulated radiation. UV-treated skin was examined clinically for UV-induced erythema, histologically for the presence of sunburn cells or Langerhans cell distributions, or biochemically for UV induced DNA damage. RESULTS: Application of green tea extracts resulted in a dose dependent inhibition of the erythema response evoked by UV radiation. The (-) epigallocatechin-3-gallate (EGCG) and (-)-epicatechin-3-gallate (ECG) polyphenolic fractions were most efficient at inhibiting erythema, whereas (-) epigallocatechin (EGC) and (-)-epicatechin (EC) had little effect. On histologic examination, skin treated with green tea extracts reduced the number of sunburn cells and protected epidermal Langerhans cells from UV damage. Green tea extracts also reduced the DNA damage that formed after UV radiation. CONCLUSION: Polyphenolic extracts of green tea are effective chemopreventive agents for many of the adverse effects of sunlight on human health and may thus serve as natural alternatives for photoprotection. PMID- 11209111 TI - Family history of psoriasis, stressful life events, and recent infectious disease are risk factors for a first episode of acute guttate psoriasis: results of a case-control study. AB - BACKGROUND: The association of guttate psoriasis with streptococcal pharyngitis is well accepted. The association of other risk factors is less well defined. OBJECTIVE: We attempted to provide an estimate of the risk for guttate psoriasis associated with a recent infectious disease and to explore other potential risk factors, including family history of psoriasis and psychologic stress. METHODS: This was a case-control study. Cases were patients with a first diagnosis ever of acute guttate psoriasis, made by a dermatologist. Controls were patients newly diagnosed as having dermatologic conditions other than psoriasis and seen in the same outpatient services as the cases. Inclusion of cases and controls was restricted to patients older than 16 years. The Holmes and Rahe Social Readjustment Rating Scale was used to assess stressful life events during the 6 months before diagnosis. A total of 73 cases (median age, 26 years) and 430 controls (median age, 28 years) were included in the analysis. RESULTS: A family history of psoriasis was strongly associated with guttate psoriasis, the multivariate odds ratio being 7.0 (95% confidence interval, 3.7-13.5) for subjects who reported a history of the disease in parents or siblings. Stressful life events were also associated with guttate psoriasis. The multivariate odds ratio was 1.7 (95% confidence interval, 0.8-3.6) for subjects scoring 41 to 100 and 2.6 (95% confidence interval, 1.3-5.2) for those scoring more than 100 on the Holmes and Rahe Scale. The risk increased with the reported history of any infectious disease. The analysis of specific diagnoses documented a high and significant association with acute pharyngitis, the adjusted odds ratio being 7.8 (95% confidence interval, 1.8-32.5). CONCLUSION: The study confirmed that recent pharyngeal infection is a risk factor for guttate psoriasis. It also documented the strong association between guttate psoriasis and a family history of psoriasis. Finally, the study added evidence to the belief that stressful life events may represent risk factors for the onset of psoriasis. By relying on the clinical diagnosis we possibly underestimate the association of guttate psoriasis with infection. PMID- 11209112 TI - Beliefs and perceptions of patients with acne. AB - BACKGROUND: There is a paucity of information on the knowledge and understanding of patients with acne about their condition. OBJECTIVE: The objective of this study is to evaluate the knowledge, beliefs, and perceptions of acne patients regarding their understanding of acne pathogenesis, sources of information, treatment options, and expectations. METHODS: Patients referred to a community based dermatologist for management of acne vulgaris completed a self-administered questionnaire. Responses were correlated with demographic and clinical information. RESULTS: Seventy-four percent of patients waited more than 1 year before seeking medical attention for acne. Nonprescription products used most frequently were cleansers, acne pads, and lotions. Acne was most often believed to be caused by hormonal and genetic factors, although diet, poor skin hygiene, and infection were also implicated. Information on acne was obtained primarily from family physicians, mass media, friends, and family, but was largely believed to be inadequate. Acne was believed to be curable by 49% of patients with an anticipated treatment duration of less than 6 months. Male patients and those with severe acne preferred systemic therapy compared with female patients and those with lesser grades of acne. CONCLUSION: There is a need for accessible, accurate, community-based education on the natural history of acne, pathogenesis, risk of sequelae, the effectiveness and expected duration of treatment, and the importance of prompt medical attention. PMID- 11209113 TI - Immunopathologic characterization of the tissue response in endemic pemphigus foliaceus (fogo selvagem). AB - BACKGROUND: The research on endemic pemphigus foliaceus (fogo selvagem) has mainly focused on the humoral immune response, but little attention has been given to the function of cell-mediated immune response and the nature of the cellular elements of the tissue reaction in the lesions of fogo selvagem. OBJECTIVE: The purpose of this study was the immunophenotype characterization of the inflammatory cells as well as the expression of adhesion molecules and HLA-DR in the perilesional and lesional skin of fogo selvagem. METHODS: Twenty biopsy specimens of lesional and perilesional skin were analyzed by immunohistochemical techniques. The panel of monoclonal antibodies consisted of CD8, CD4, CD1a, HLA DR, IL-2R, LFA-1, ICAM-1, and PAN-B. RESULTS: The semiquantitative analysis of the cell population revealed a predominance of CD4 T lymphocytes in the tissue response of perilesional and lesional skin. The population of epidermal Langerhans cells was decreased in lesional skin when compared with the perilesional skin, whereas CD1a(+) dermal dendritic cells predominated in lesional skin. Keratinocyte expression of ICAM-1 and HLA-DR was negative in both lesional and perilesional skin. CONCLUSION: The overall results suggest the participation of the cell-mediated immunity in endemic pemphigus foliaceus (fogo selvagem). The lack of keratinocyte ICAM-1 expression may be related to the pattern of cytokines secreted by the CD4(+) T cells of the tissue reaction in fogo selvagem. PMID- 11209114 TI - Evaluation of sentinel lymph node status in spindle cell melanomas. AB - BACKGROUND: The propensity for spindle cell melanoma to metastasize to the lymph node is relatively low despite its relative thick depth. To date, there are no published reports on the sentinel lymph node (SLN) status in patients diagnosed with spindle cell melanoma and desmoplastic malignant melanoma (DMM). OBJECTIVE: Our purpose was to report our experience on the SLN status in spindle cell melanoma and DMM. METHODS: We undertook a retrospective database and medical record review from Oct 21, 1993 to Sept 29, 1999. At the University of California at San Francisco Melanoma Center, patients with tumor thickness greater than 1 mm or less than 1 mm with high-risk features are managed with preoperative lymphoscintigraphy, selective SLN dissection, and wide excision. RESULTS: Of 29 patients diagnosed with spindle cell melanoma and DMM, 28 had negative SLNs and are free of disease except for one patient who experienced splenic, bony, and brain metastases. The mean follow-up in this population was 16.5 and 11 months, respectively. CONCLUSION: Our preliminary findings show that SLNs from patients diagnosed with spindle cell melanoma and DMM only rarely harbor micrometastasis despite their relative thickness. A larger number of cases from multicenter databases may further define the true biology of SLNs in this melanoma variant. PMID- 11209115 TI - CD4(+)CD7(-) T cells compose the dominant T-cell clone in the peripheral blood of patients with Sezary syndrome. AB - BACKGROUND: Absence of CD7 antigen expression in T cells defines a subset of normal CD4(+) CD45RO(+) CD45RA(-) memory cells and is furthermore observed in Sezary syndrome (SS). OBJECTIVE: Our purpose was to identify circulating T-cell clones in patients with SS and to elucidate whether the dominant T-cell clones express the CD7 antigen. METHODS: Peripheral blood lymphocytes of patients with SS were analyzed by two-color flow cytometry using antibodies to the V beta region of the T cell receptor (TCR) in combination with an antibody to CD7. In addition, T cells were analyzed for TCR-gamma gene rearrangement by polymerase chain reaction (PCR) techniques. RESULTS: Clonal T-cell expansion was detected in 7 patients with SS by immunostaining of the TCR V beta regions. PCR analysis confirmed the presence of dominant T cell clones. Double-immunostaining revealed that in each case cells of the clonal V beta TCR rearrangement homogeneously express the CD4(+)CD7(-) phenotype. Furthermore, CD4(+)CD7(-) cells express the CD15s antigen but lack expression of CD26 and CD49d. CONCLUSION: Expansion of clonal T cells strongly correlates with the expansion of CD4(+)CD7(-) T cells in 7 tested patients with SS. This supports our model that a subset of late differentiated, normal CD4(+)CD7(-) memory T cells may represent the physiologic counterpart of Sezary cells. Monitoring of circulating T cells with the CD4(+)CD7(-)CD15s(+)CD26(-)CD49d(-) phenotype proved to be useful for the identification of clonal T cells in patients with SS. PMID- 11209116 TI - Imiquimod 5% cream in the treatment of Bowen's disease. AB - BACKGROUND: Large-diameter lesions of Bowen's disease at sites such as the shin may be difficult to treat surgically and may require alternate treatment modalities. OBJECTIVE: We investigated whether imiquimod 5% cream, a topical immune response modifier that stimulates the production of interferon alfa and other cytokines, is an effective topical treatment for Bowen's disease. METHODS: This was a phase II, open-label study in 16 patients, treating a single biopsy proven plaque of Bowen's disease that was 1 cm or larger in diameter, with once daily self-application of imiquimod 5% cream for 16 weeks. A biopsy was performed on the treated area 6 weeks after the end of treatment, with patient follow-up at 3 and 6 months. Lymphocyte CD4/CD8 ratios were analyzed in pretreatment and posttreatment biopsy specimens by immunophenotyping the lymphocytic infiltrate. RESULTS: Sixteen patients with Bowen's disease lesions ranging from 1 to 5.4 cm in diameter (0.7-21.6 cm(2) in area) were treated. Fifteen of these lesions were on the legs, and one was on the shoulder. Fourteen of the 15 patients (93% per protocol analysis) had no residual tumor present in their 6-week posttreatment biopsy specimens. One patient died of unrelated intercurrent illness before a biopsy specimen could be obtained. The median CD4/CD8 lymphocyte ratio in pretreatment biopsy specimens was 2:1, and this was reversed to a median of 1:2.2 in the posttreatment specimens. Ten patients completed 16 weeks of treatment, but 6 patients ceased treatment early (between 4 and 8 weeks) because of local skin reactions. CONCLUSION: Imiquimod 5% cream appears to be an effective treatment for Bowen's disease on the lower limbs. The 93% positive treatment response in biopsy-proven cases (excludes patient who died from an intercurrent illness who did not undergo a posttreatment biopsy) compares favorably with other current treatment modalities. The dosing schedule and length of treatment for Bowen's disease require further evaluation. PMID- 11209117 TI - Treatment of prurigo nodularis with topical capsaicin. AB - BACKGROUND: Prurigo nodularis is an eruption of lichenified or excoriated nodules caused by intractable pruritus that is difficult to treat. Therefore the antipruritic efficacy of capsaicin seemed to be of particular interest because this alkaloid, extractable from red pepper, interferes with the perception of pruritus and pain by depletion of neuropeptides in small sensory cutaneous nerves. OBJECTIVE: The aim of this concentration- and regimen-ranging study was to evaluate the efficacy, safety, and practicability of capsaicin in the topical treatment of prurigo nodularis in a large series of patients. METHODS: A total of 33 patients with prurigo nodularis of various origins were selected to receive capsaicin (0.025% to 0.3%) 4 to 6 times daily for 2 weeks up to 10 months. The consecutive follow-up period was up to 6 months. In 7 patients, skin biopsy specimens were taken before, during, and after therapy and investigated histologically, immunohistochemically, and ultrastructurally. RESULTS: All 33 patients could be evaluated for efficacy. After cessation of the symptoms of neurogenic inflammation, such as burning sensations or erythema, all of them experienced a complete elimination of pruritus within 12 days. In addition, capsaicin largely contributed to the gradual healing of the skin lesions. After discontinuation of the therapy, pruritus returned in 16 of 33 patients within 2 months. At the ultrastructural level, no degenerative changes of cutaneous nerves could be found during or after capsaicin therapy. Depletion of substance P was demonstrated by confocal laser scanning microscopy thus confirming the specific effect of capsaicin in vivo. CONCLUSION: Topical treatment of prurigo nodularis with capsaicin proved to be an effective and safe regimen resulting in clearing of the skin lesions. PMID- 11209118 TI - Single-blind, randomized, prospective study on terbinafine and itraconazole for treatment of dermatophyte toenail onychomycosis in the elderly. AB - BACKGROUND: The 2 most common agents used to treat dermatophyte onychomycosis of the toe are terbinafine (continuous) and itraconazole (pulse). Although comparative studies have been performed evaluating the efficacy of these 2 agents in adults, no such studies have been reported specifically in the elderly subset. OBJECTIVE: This prospective, randomized, single-blind, non--industry-sponsored, comparative study evaluated the efficacy and safety of terbinafine (continuous) and itraconazole (pulse) therapies in the treatment of dermatophyte onychomycosis of the toe in the elderly population. METHODS: Elderly patients (> or =60 years old) with dermatophyte onychomycosis of at least 1 great toe were randomly assigned to receive either terbinafine 250 mg/day for 12 weeks or itraconazole (pulse) 200 mg twice a day for 1 week, given for 3 pulses. At month 6 from the start of therapy, if there was less than 50% reduction in the affected nail plate area compared with baseline, or if there was less than 3 mm outgrowth of unaffected nail plate as measured in midline, then patients who had been administered terbinafine (continuous) therapy were given an extra 4 weeks of the drug (total of 16 weeks of therapy), and those who had received itraconazole (pulse) therapy were given an extra pulse (fourth pulse). Patients were evaluated at 1.5, 3, 6, 12, and 18 months from the start of therapy. The efficacy measures included mycologic cure rate and clinical efficacy (mycologic cure plus clinical cure or clinical improvement so that 10% or less of nail plate was clinically involved). RESULTS: There were 101 elderly patients enrolled in the study with 50 and 51 patients receiving terbinafine and itraconazole, respectively. The terbinafine group consisted of 28 men and 22 women, age (mean +/- standard error [SE]) 68.0 +/- 0.9 years, duration of onychomycosis (mean +/- SE) 18.2 +/- 1.4 years, number of nails involved (mean +/- SE) 5.5 +/- 0.5, and percent baseline nail plate area involved (mean +/- SE) 67.5% +/- 4.2%. The corresponding figures for the itraconazole (pulse) group were 24 men and 27 women, age (mean +/- SE) 68.8 +/- 0.8 years, duration of onychomycosis (mean +/- SE) 16.1 +/- 1.7 years, number of nails involved (mean +/- SE) 6.0 +/- 0.7, and percent baseline nail plate area involved (mean +/- SE) 74.9% +/- 3.8%, respectively, with no significant difference between the groups. At month 6, the number of patients that required an extra 4 weeks of terbinafine in the allylamine group or an extra itraconazole pulse in the triazole group was 13 of 50 and 23 of 51, respectively. The mycologic cure rate and clinical efficacy at 18 months from the start of therapy for the terbinafine group were 64.0% and 62.0%, respectively. The corresponding figures for the itraconazole (pulse) group were 62.7% and 60.8%, respectively, with no significant difference between the 2 groups. There were no dropouts during therapy. For both groups the drug appeared safe with no significant adverse events (AEs) or clinically significant laboratory abnormalities. All the AEs were mild and transient. There was high compliance with both regimens. CONCLUSIONS: In the elderly, for the treatment of dermatophyte toe onychomycosis, both terbinafine (continuous) and itraconazole (pulse) therapies are effective, safe, and associated with high compliance. PMID- 11209119 TI - Single-blind, randomized, prospective study of sequential itraconazole and terbinafine pulse compared with terbinafine pulse for the treatment of toenail onychomycosis. AB - OBJECTIVE: Efficacy and safety of sequential pulse therapy with itraconazole and terbinafine were compared with pulse terbinafine alone in the treatment of toenail onychomycosis. METHODS: This was a 72-week prospective, single-blind, randomized, multicenter, comparative, parallel group, nonindustry-sponsored trial. A total of 190 patients were recruited from 3 outpatient dermatology offices in North America. Patients were at least 18 years old and had a clinical and mycologic diagnosis of dermatophyte toenail onychomycosis. Patients were randomly assigned to receive sequential pulse therapy (IIT) with 2 pulses of itraconazole followed by 1 or 2 pulses of terbinafine (itraconazole pulse is 200 mg twice daily for 1 week and terbinafine pulse is 250 mg twice daily for 1 week) versus 3 or 4 pulses of terbinafine (TTT). Main outcome measures at week 72 evaluated mycologic cure rate (negative light microscopy and culture), clinical cure (nail appears completely or totally normal), complete cure (clinical and mycologic cure), and effective therapy (mycologic cure and clinical response with at least 5 mm of new, uninvolved nail growth). RESULTS: At week 72, in the IIT versus TTT groups, the mycologic cure rate was 54 of 75 (72.0%) versus 44 of 90 (48.9%), clinical cure rate was 42 of 75 (56.0%) versus 35 of 90 (38.9%), effective therapy 49 of 75 (65.3%) versus 41 of 90 (45.6%), and complete cure 39 of 75 (52.0%) versus 29 of 90 (32.2%), respectively. Both regimens were well tolerated with no new adverse effects being identified. The rate of permanent discontinuation of therapy because of adverse effects was 2 of 81 (2.5%) with IIT and 2 of 95 (2.1%) with TTT. Each of the adverse effects normalized over time. The number of patients who reported an adverse effect in the 2 groups was 12 of 81 (14.8%) versus 22 of 95 (23.2%), respectively. All these adverse effects were reversible and mild to moderate in severity. CONCLUSION: Sequential pulse therapy with itraconazole and terbinafine is effective and safe for the treatment of dermatophyte toenail onychomycosis. PMID- 11209120 TI - A clinical and histologic comparison of electrosurgical and carbon dioxide laser peels. AB - BACKGROUND: A radiofrequency-controlled electrosurgical device (ESD) has been adapted for skin peeling. A high-voltage, low-amperage current converts an irrigant into an ionized vapor, causing molecular dissociation and superficial damage in adjacent tissue. OBJECTIVE: We compared the clinical and histologic effects of a scanning carbon dioxide (CO(2)) laser (ESC/Sharplan 40C) and the ESD (Visage Cosmetic Surgery System, Arthrocare). METHODS: This study was a matched clinical trial involving 9 subjects. Two strips (2 x 1 cm) of skin on the temple were alternately assigned to receive 2 passes with either the CO(2) laser (Silktouch mode, 260 handpiece, fluence 15 J/cm(2), 10 mm(2)) or the ESD (125 V = setting 4, 5 mm handpiece). Strips were wiped with moist gauze after the first pass, and 4-mm punch biopsy specimens were taken immediately and after 3 months. Clinical assessment of re-epithelialization, erythema, and hyperpigmentation was made at 1, 2, 4, and 12 weeks. RESULTS: Median erythema scores were significantly greater in skin treated with the CO(2) laser. Histologic examination showed greater epidermal loss and a significantly thicker zone of underlying thermal damage (average difference, 63 microm; 95% confidence interval, 40-87; P =.0002) in skin treated with the CO(2) laser compared with skin treated with the ESD. After 3 months, a band of superficial dermal fibrosis was thicker in skin treated with the CO(2) laser (average difference, 170 microm; 95% confidence interval, 69 271; P =.0075). CONCLUSION: Two passes with the ESD elicited a more superficial skin peel than the CO(2) laser. Despite minimal thermal damage, superficial dermal fibrosis was seen at 3 months in skin treated with the ESD. PMID- 11209121 TI - Risk of synchronous and metachronous second nonmelanoma skin cancer when referred for Mohs micrographic surgery. AB - BACKGROUND: Patients with basal cell carcinoma and cutaneous squamous cell carcinoma are at substantial risk for the onset of a second nonmelanoma skin cancer (NMSC). OBJECTIVE: Our purpose was to determine the incidence of multiple (synchronous) NMSC at presentation to an academic Mohs micrographic surgery referral center and to note the incidence of second lesions occurring in a metachronous fashion. METHODS: A retrospective study was conducted of 456 consecutive patients who presented for Mohs surgery over a 2-year period. Patients were assessed at initial visits for the presence of multiple NMSCs and were subsequently examined over 2 years for the onset of new NMSCs. RESULTS: More than 39% of patients initially referred for Mohs surgery with a basal cell or squamous cell carcinoma either presented with multiple primary lesions or experienced a subsequent NMSC within 2 years. These tumors were divided almost equally between multiple primary NMSC at presentation and subsequent (metachronous) tumors. CONCLUSION: Patients referred for Mohs surgery in an academic setting are a select group at extremely high risk of additional NMSCs at or shortly after presentation for the index lesion. PMID- 11209122 TI - MIB-1 monoclonal antibody to determine proliferative activity of Ki-67 antigen as an adjunct to the histopathologic differential diagnosis of Spitz nevi. AB - BACKGROUND: The histopathologic differential diagnosis of Spitz nevus (SN) from malignant melanoma (MM) may be difficult. OBJECTIVE: Our purpose was to determine the staining pattern and usefulness of MIB-1 antibody, which recognizes Ki-67 antigen in formalin-fixed, paraffin-embedded tissue, as an adjunct to the histopathologic differential diagnosis of SN. METHODS: Twenty-five compound SNs, 27 MMs, and 26 compound nondysplastic melanocytic nevi (MNs) were immunostained with the MIB-1 antibody. RESULTS: The mean counts of MIB-1--stained tumor cells of the epidermal and dermal components, both alone and together, were significantly lower in SNs and MNs than in MMs (P <.0001). The dermal counts showed the best discriminating power. In addition, the mean dermal/epidermal count ratios for MIB-1 in SNs and MNs (0.25 and 0.23, respectively) were significantly lower than the corresponding ratio (0.94) in MMs (P <.0001). CONCLUSION: MIB-1-stained tumor cell counts, especially of the dermal component, and dermal/epidermal MIB-1 count ratios may be helpful as an adjunct to the histopathologic differential diagnosis of SN. PMID- 11209124 TI - Langerhans cell histiocytosis. PMID- 11209123 TI - American Academy of Dermatology Consensus Conference on UVA protection of sunscreens: summary and recommendations. Washington, DC, Feb 4, 2000. PMID- 11209125 TI - Sun protection practices in preadolescents and adolescents: a school-based survey of almost 25,000 Connecticut schoolchildren. AB - Sun protection practices in children and adolescents fall well below national recommendations. We present the results of a survey of sun protection use and other health-related behaviors in a sample of Connecticut Caucasian students aged 9 through 18 years (N = 24,645). Our objectives were to estimate the prevalence of sun protection use and to evaluate the relationship between sun protection use and health-risk behaviors and attitudes about appearance. We present data from 1988 through 1995 from the Connecticut Health Check, a health risk appraisal survey sponsored by the Connecticut Department of Public Health. Students enrolled in public and private elementary junior as well as senior high schools took the self-administered anonymous survey, which included multiple-choice questions about use of sun protection, cigarettes, and alcohol and about body image and self-esteem. We report prevalence proportions for use of sun protection by demographic features. We compared the proportion of students in 3 categories of outcome (always, sometimes, and never use sun protection) who reported various health-risk behaviors. Twenty percent of the sample reported always using sun protection; this is well below national goals set forth in the Healthy People 2000 recommendations. Sun protection use was inversely related to age and was higher among girls than boys at all ages. At all ages, students who did not use sun protection were more likely than those who did to report other health risk behaviors, such as use of cigarettes and alcohol. The data suggested that use of sun protection is associated with positive attitudes about appearance and self image. Use of sun protection may be one component of an overall mode of health awareness and behavior. Programs promoting safe sun practices should target boys and be integrated into an overall campaign aimed at other risk-taking behaviors. PMID- 11209126 TI - Surgical pearl: preventing self-inflicted injuries to the dermatologic surgeon. PMID- 11209127 TI - Surgical pearl: the vertical mattress tip stitch. PMID- 11209129 TI - HTLV-I-associated granulomatous T-cell lymphoma in a child. AB - Adult T-cell leukemia/lymphoma (ATLL) is a T-cell malignancy closely associated with human T-cell lymphotropic virus-1 (HTLV-I). Because of its long latency period, ATLL occurs almost exclusively in adults. We report a case of a 13-year old boy with an 8-year history of skin eruptions. After complete evaluation, a diagnosis of HTLV-I-associated lymphoma/leukemia was made. The T-cell lymphoma exhibited a granulomatous histomorphology. There have been very few reports of ATLL presenting in childhood and none, to our knowledge, demonstrating granulomatous histology. We conclude that ATLL may rarely present as a chronic granulomatous eruption in a child. PMID- 11209130 TI - Pyoderma gangrenosum associated with biphenotypic acute leukemia. AB - Pyoderma gangrenosum is a neutrophilic dermatosis that may be associated with myeloid malignancies. Less information is available about the association of pyoderma gangrenosum with lymphoid malignancies. We present, to our knowledge, the first case of pyoderma gangrenosum associated with biphenotypic acute leukemia wherein the malignant cells show a phenotype specific for myelogenic and lymphocytic leukemia. Histopathologic examination revealed rather nonspecific features without involvement of leukemic cells in the skin lesions. Treatment with systemic steroids was followed by characteristically rapid healing of the skin lesion. PMID- 11209131 TI - Mycosis fungoides in identical twins. PMID- 11209132 TI - Pseudoxanthoma elasticum: significance of limited phenotypic expression in parents of affected offspring. AB - The inheritance pattern of pseudoxanthoma elasticum (PXE) is controversial. Inheritance patterns are confounded by delayed diagnosis and mild or limited phenotypic expression among certain family members. Because testing for the genetic mutation(s) responsible for PXE is not routine, genetic counseling must be done with caution. We describe 4 families in which one or more children were diagnosed with PXE. Detailed examination of the parents was carried out, including skin biopsy and ophthalmologic examination. In 3 of the 4 families, one parent had limited phenotypic expression, such as ocular findings without skin lesions or very mild skin lesions with no ocular findings. In the other family, one parent had very mild skin and ocular disease. All 4 affected parents had diagnostic skin biopsy findings. In none of the 4 families was the inheritance pattern clear-cut. Although the inheritance pattern of PXE has been debated, clinically significant stigmata of PXE, which are not always readily apparent, can occur in successive generations. Therefore all first-degree relatives of affected patients should receive a full dermatologic examination as well as a funduscopic examination. If even mild typical skin or eye findings are present, then skin biopsy should be performed. PMID- 11209133 TI - Immunohistochemical detection of the c-met proto-oncogene product in the congenital melanocytic nevus of an infant with neurocutaneous melanosis. AB - Transgenic mice overexpressing hepatocyte growth factor/scatter factor (HGF/SF) demonstrate extensive pigmented nevi in both skin and leptomeninges of the central nervous system resembling human neurocutaneous melanosis. We immunohistochemically detected HGF/SF receptor, Met, in a congenital nevus of an infant with neurocutaneous melanosis, indicating that deregulation of HGF/SF-Met signaling in the critical period of development may lead to this fatal syndrome. PMID- 11209134 TI - No further studies are required: additional notes on avoiding manuscript rejection. PMID- 11209135 TI - "Devotional dermatoses": a new nosologic entity? PMID- 11209136 TI - Transplantation of autologous cultured melanocytes for treatment of large segmental vitiligo. PMID- 11209137 TI - Extraordinary delayed bleeding occurring after shave excision. PMID- 11209138 TI - Foscarnet-associated eosinophilic folliculitis in a patient with AIDS. PMID- 11209139 TI - Trichoblastoma or trichoblastic carcinoma? PMID- 11209140 TI - Longitudinal melanonychia in children. PMID- 11209141 TI - UVA1 for atopic dermatitis: medium dose superior to low dose. PMID- 11209142 TI - Should pentoxifylline be regarded as an effective treatment for Schamberg's disease? PMID- 11209143 TI - Signet-ring cell formation in cutaneous neoplasms. PMID- 11209144 TI - How to manage atrial fibrillation: an update on recent clinical trials. AB - The latter half of the 1990s was a time of extraordinary progress in the understanding and management of atrial fibrillation (AF). Evidence that "AF begets AF" has generated considerable interest regarding the mechanisms responsible for this phenomenon and has sparked the development of new concepts in both pharmacologic and nonpharmacologic therapy. The recognition that, in some patients, AF is initiated and possibly maintained by atrial tachycardia originating in the pulmonary veins has challenged accepted notions regarding the mechanisms responsible for arrhythmia. New antiarrhythmic drugs, devices, ablation techniques, and pacing techniques have been developed and tested. Strategies for the use of existing therapies have been evaluated, and new indications for existing therapies are under consideration. This article reviews several studies published in 1999 and 2000 that addressed the mechanisms and the management of AF. PMID- 11209145 TI - Value of exercise testing in assessing clinical state and prognosis in hypertrophic cardiomyopathy. AB - Hypertrophic cardiomyopathy (HCM) is a genetic disease of the sarcomeric contractile proteins. A majority of patients with HCM are limited in terms of functional capacity, and a minority of these patients die suddenly. The main aims of management are symptom alleviation and prevention of sudden cardiac death. In patients with HCM, cardiopulmonary exercise testing provides a much more accurate index of functional capacity than New York Heart Association classification status, and it is useful in assessing symptoms after various therapeutic strategies have been implemented. Exercise testing is also valuable in identifying patients with HCM who are at high risk of sudden cardiac death and is an integral part of the algorithm in risk stratification and delivery of prophylactic therapy. Also, cardiopulmonary exercise testing plays an important role in differentiating HCM from other conditions associated with left ventricular hypertrophy, such as physiologic athlete's heart. Therefore, during the last few years, cardiopulmonary exercise testing has provided insights into the diagnosis, determinants, and mechanisms of exercise limitation in HCM. This understanding aids physicians in targeting therapy and developing new treatment modalities. PMID- 11209146 TI - Coronary magnetic resonance angiography. AB - Despite advances in both prevention and treatment, cardiovascular disease remains the leading cause of morbidity and mortality in the United States. The current gold standard for the diagnosis of coronary artery disease is the x-ray coronary angiogram, which is both costly and associated with a small risk of morbidity. More than 1 million Americans are referred for this test annually, and despite the availability of numerous noninvasive tests to identify patients with coronary artery disease, > or =35% of patients referred for this test are found not to have disease. It therefore would be beneficial to use a noninvasive test to allow the presence of coronary atherosclerosis to be determined directly. Coronary magnetic resonance angiography, a technique that is aimed at establishing a noninvasive test for the assessment of significant coronary stenoses, obviates the risks of patient exposure to radiation of x-ray angiography and therefore represents a major step forward in diagnostic cardiology. PMID- 11209147 TI - Etiology, evaluation, and management of acute myocarditis. AB - The evaluation and management of acute myocarditis remain two of the most difficult challenges that general internists and cardiologists face today. Although the majority of cases are subclinical and self-limited, the true prevalence of myocarditis in the general population is unknown. In its most severe form, patients with myocarditis may present with rapidly progressive heart failure, cardiogenic shock, or complex arrhythmia. Indeed, acute myocarditis should be in the differential diagnosis of acute heart failure, particularly in young and previously healthy individuals. PMID- 11209149 TI - Complicated mitral valve repairs. AB - The standard of care for mitral regurgitation secondary to degenerative valvular disease is mitral valve repair whenever possible. Mitral valve repair is associated with better left ventricular function preservation, fewer complications, and improved survival as compared with mitral valve replacement. Most of the mitral valve pathology involves the posterior leaflet or annulus and usually can be repaired by using standard valve repair techniques. Difficulties may arise when trying to repair the somewhat uncommon anterior leaflet prolapse or calcified mitral annulus. This article reviews these more complex mitral valve repair techniques and their outcomes. PMID- 11209148 TI - ABCs of cardiovascular disease risk management. AB - The past 20 years have witnessed a marked decline in morbidity and mortality from cardiovascular disease. This decline has been due in large part to advances in coronary risk factor modification and a better understanding of the atherosclerotic process. Compelling scientific and clinical trial evidence proves that comprehensive risk factor modification extends patient survival and reduces cardiovascular and cerebrovascular events. This article reviews the ABCs of optimal medical and lifestyle management in patients with documented atherosclerotic vascular disease as well as in those adults who are at increased risk for the development of cardiovascular disease, based on contemporary clinical trial evidence. PMID- 11209153 TI - Choice of revascularization strategy for patients with coronary artery disease. PMID- 11209154 TI - Former addicts face barriers to treatment for HCV. PMID- 11209155 TI - Win or lose, Internet gambling stakes are high. PMID- 11209156 TI - What's the connection? No easy answers for people with eating disorders and drug abuse. PMID- 11209161 TI - Underuse of beta-blockers following myocardial infarction. PMID- 11209163 TI - Treatment strategies for migraine headache. PMID- 11209164 TI - Treatment strategies for migraine headache. PMID- 11209166 TI - Methodological issues in trials of acupuncture. PMID- 11209167 TI - Methodological issues in trials of acupuncture. PMID- 11209169 TI - Demands of an aging population for critical care and pulmonary services. PMID- 11209170 TI - Demands of an aging population for critical care and pulmonary services. PMID- 11209172 TI - Subsequent criminal activity among violent misdemeanants who seek to purchase handguns: risk factors and effectiveness of denying handgun purchase. AB - CONTEXT: Some states prohibit the purchase of handguns by persons convicted of selected misdemeanor crimes, but most do not. California has denied handgun purchases by violent misdemeanants since 1991; the effectiveness of these policies is unknown. OBJECTIVE: To determine the risk factors for new criminal activity among violent misdemeanants who seek to purchase handguns and whether denial of handgun purchase by violent misdemeanants affects their risk of arrest for new crimes, particularly gun and/or violent crimes. DESIGN: Retrospective, population-based cohort study. SETTING AND SUBJECTS: Persons aged 21 to 34 years who sought to purchase a handgun through a licensed dealer in California during 1989-1991 and who had at least 1 violent misdemeanor conviction in the preceding 10 years. The study cohorts consisted of 986 persons whose purchase applications were made in 1991 and were denied (denied persons) and 787 persons whose purchase applications were made in 1989-1990 and were approved (purchasers). MAIN OUTCOME MEASURES: Incidence and relative risk of first arrest in California for new gun and/or violent crimes and for nongun, nonviolent crimes during a 3-year follow-up after actual or attempted handgun purchase. RESULTS: During the 3-year follow-up, 546 (33.0%) of 1654 subjects with follow-up information were arrested for a new crime, including 296 (31.9%) of 927 denied persons and 250 (34.4%) of 727 purchasers. After adjusting for differences in age, sex, and prior criminal history, purchasers were more likely than denied persons to be arrested for new gun and/or violent crimes (relative hazard [RH], 1.29; 95% confidence interval [CI], 1.04-1.60), but not for nongun, nonviolent crimes (RH, 0.96; 95% CI, 0.78 1.19). In both groups, risk of arrest was strongly related to age and number of convictions accrued prior to actual or attempted handgun purchase. CONCLUSION: Our results indicate that denial of handgun purchase to violent misdemeanants is associated with a specific decrease in risk of arrest for new gun and/or violent crimes. PMID- 11209173 TI - Relation between pediatric experience and treatment recommendations for children and adolescents with kidney failure. AB - CONTEXT: Children and adolescent patients with renal failure are frequently cared for by adult subspecialists. While peritoneal dialysis is used in less than 17% of adults with kidney failure, it is the preferred dialysis treatment for children. National data show that 45% of children receiving dialysis are treated with peritoneal dialysis and pediatric nephrologists report its use in 65% of patients receiving dialysis. Whether differences in peritoneal dialysis use among children are due to the pediatric experience of the clinician has not been examined. OBJECTIVE: To assess whether the pediatric experience of nephrologists directly affects treatment recommendations for children with kidney failure. DESIGN: Cross-sectional survey using 10 case vignettes per survey based on random combinations of 8 patient characteristics (age, sex, race, distance from facility, cause of renal failure, family structure, education, and compliance). SETTING AND PARTICIPANTS: National random sample of office-, hospital-, and academic medical center-based adult and pediatric nephrologists, stratified by geographic region and conducted June to November 1999. Of 519 eligible physicians, 316 (61%) responded, including 191 adult and 125 pediatric nephrologists. MAIN OUTCOME MEASURE: Treatment recommendations for peritoneal dialysis vs hemodialysis, compared based on nephrologists' pediatric experience. RESULTS: After controlling for patient characteristics, pediatric nephrologists were 60% more likely than adult nephrologists to recommend peritoneal dialysis for identical patients (odds ratio, 1.61; 95% confidence interval, 1.35-1.92). This was true regardless of dialysis training, years in practice, practice setting, geography, or patient characteristics. CONCLUSIONS: Our data indicate that pediatric specialization of clinicians influences treatment recommendations for children and adolescents with end-stage renal disease. Referring children to adult subspecialists may lead to differences in treatment choices and processes of care. PMID- 11209174 TI - Discrepancies between patient and physician estimates for the success of stem cell transplantation. AB - CONTEXT: Stem cell transplantation is associated with considerable morbidity and mortality. The extent to which patients and their physicians correctly estimate these risks is unknown. OBJECTIVE: To measure the expectations of patients and physicians prior to stem cell transplantation and correlate them with actual outcomes after transplantation. DESIGN: Prospective cohort study with baseline questionnaire administered July 1996 through November 1999 and follow-up to May 2000. SETTING: Tertiary care transplant center in the United States. PARTICIPANTS: Of 458 surveys mailed, evaluable returned surveys were included for 313 autologous and allogeneic stem cell transplantation patients and their physicians. MAIN OUTCOME MEASURES: Patient and physician expectations prior to transplantation (measured on 6-point Likert scales) of treatment-related mortality, cure with transplantation, and cure without transplantation; actual treatment-related mortality and disease-free survival among patients with at least 1 year of follow-up after transplantation (n = 263). RESULTS: Both patients and physicians were fairly accurate in estimating treatment-related mortality when actual mortality was less than 30%. However, in situations in which mortality was higher than 30%, such as with allogeneic transplantation for intermediate or advanced disease, physician expectations were lower, while patients remained optimistic. Similarly, physicians provided lower estimates of disease-free survival in cases of intermediate or advanced disease while patient expectations remained high and constant regardless of disease stage. CONCLUSIONS: Patients and their physicians have the most concordant and accurate expectations when the outcome of stem cell transplantation is likely to be favorable. However, patients with more advanced disease fail to recognize the higher risks associated with their situations. PMID- 11209176 TI - Second-trimester ultrasound to detect fetuses with Down syndrome: a meta analysis. AB - CONTEXT: Second-trimester prenatal ultrasound is widely used in an attempt to detect Down syndrome in fetuses, but the accuracy of this method is unknown. OBJECTIVE: To determine the accuracy of second-trimester ultrasound in detecting Down syndrome in fetuses. DATA SOURCES: English-language articles published between 1980 and February 1999 identified through MEDLINE and manual searches. STUDY SELECTION: Studies were included if they recorded second-trimester findings of ultrasonographic markers, chromosomal abnormalities, and clinical outcomes for a well-described sample of women. A total of 56 articles describing 1930 fetuses with Down syndrome and 130 365 unaffected fetuses were included. DATA EXTRACTION: Articles were independently reviewed, selected, and abstracted by 2 reviewers. Discrepancies in data abstraction were resolved by consensus with a third reviewer. Overall estimates of sensitivity, specificity, and positive and negative likelihood ratios were calculated for the following markers: choroid plexus cyst, thickened nuchal fold, echogenic intracardiac focus, echogenic bowel, renal pyelectasis, and humeral and femoral shortening. Results were stratified by whether markers were identified in isolation or in conjunction with fetal structural malformations. DATA SYNTHESIS: When ultrasonographic markers were observed without associated fetal structural malformations, sensitivity for each was low (range, 1%-16%), and most fetuses with such markers had normal outcomes. A thickened nuchal fold was the most accurate marker for discriminating between unaffected and affected fetuses and was associated with an approximately 17-fold increased risk of Down syndrome. If a thickened nuchal fold is used to screen for Down syndrome, 15 893 average-risk women or 6818 high-risk women would need to be screened for each case of Down syndrome identified. For each of the other 6 markers, when observed without associated structural malformations, the marker had marginal impact on the risk of Down syndrome. Because the markers were detected in only a small number of affected fetuses, the likelihood of Down syndrome did not decrease substantially after normal examination findings (none of the negative likelihood ratios were significant). CONCLUSIONS: A thickened nuchal fold in the second trimester may be useful in distinguishing unaffected fetuses from those with Down syndrome, but the overall sensitivity of this finding is too low for it to be a practical screening test for Down syndrome. When observed without associated structural malformations, the remaining ultrasonographic markers could not discriminate well between unaffected fetuses and those with Down syndrome. Using these markers as a basis for deciding to offer amniocentesis will result in more fetal losses than cases of Down syndrome detected, and will lead to a decrease in the prenatal detection of fetuses with Down syndrome. PMID- 11209175 TI - Culture and immunological detection of Tropheryma whippelii from the duodenum of a patient with Whipple disease. AB - CONTEXT: Culture of Tropheryma whippelii has been established only once, in human fibroblast cell lines from a heart valve inoculum. Molecular-based diagnostic techniques, although highly sensitive, may be less specific. New diagnostic tools involving isolation of bacteria from contaminated intestinal biopsies and immunohistological detection need to be developed. OBJECTIVE: To describe a novel method for detection and culture of T whippelii strains. DESIGN, SETTING, AND SUBJECTS: Laboratory analysis of duodenal biopsy specimens from a patient with typical relapsing Whipple disease with intestinal involvement, performed Marseille, France, in March 2000. Biopsy specimens were decontaminated with antimicrobial agents and inoculated onto cell cultures. Mouse anti-T whippelii polyclonal antibodies were used to detect T whippelii in fixed specimens taken from the patient before and after relapse, compared with specimens from 10 controls. The genotype of the isolate was determined by amplification and sequencing of 2 DNA fragments (ITS and 23S rRNA). MAIN OUTCOME MEASURE: Isolation and genotyping of a new strain(s) of T whippelii from the case patient's biopsy specimens. RESULTS: A strain was grown from the case patient's intestinal specimen that has a genotype different from the first strain isolated. During 2 episodes of Whipple disease, T whippelii bacteria were detected by immunochemistry in the patient's duodenal biopsy specimens, but not in controls. CONCLUSIONS: A second strain of T whippelii has been isolated and a protocol for isolation from the intestine has been proven to be efficient. Immunodetection of T whippelii in intestinal biopsy specimens may provide a useful tool for the diagnosis and follow-up of patients with Whipple disease. Both techniques need further evaluation and confirmation. PMID- 11209177 TI - Liver transplantation and opioid dependence. PMID- 11209178 TI - Botulinum toxin as a biological weapon: medical and public health management. AB - OBJECTIVE: The Working Group on Civilian Biodefense has developed consensus-based recommendations for measures to be taken by medical and public health professionals if botulinum toxin is used as a biological weapon against a civilian population. PARTICIPANTS: The working group included 23 representatives from academic, government, and private institutions with expertise in public health, emergency management, and clinical medicine. EVIDENCE: The primary authors (S.S.A. and R.S.) searched OLDMEDLINE and MEDLINE (1960-March 1999) and their professional collections for literature concerning use of botulinum toxin as a bioweapon. The literature was reviewed, and opinions were sought from the working group and other experts on diagnosis and management of botulism. Additional MEDLINE searches were conducted through April 2000 during the review and revisions of the consensus statement. CONSENSUS PROCESS: The first draft of the working group's consensus statement was a synthesis of information obtained in the formal evidence-gathering process. The working group convened to review the first draft in May 1999. Working group members reviewed subsequent drafts and suggested additional revisions. The final statement incorporates all relevant evidence obtained in the literature search in conjunction with final consensus recommendations supported by all working group members. CONCLUSIONS: An aerosolized or foodborne botulinum toxin weapon would cause acute symmetric, descending flaccid paralysis with prominent bulbar palsies such as diplopia, dysarthria, dysphonia, and dysphagia that would typically present 12 to 72 hours after exposure. Effective response to a deliberate release of botulinum toxin will depend on timely clinical diagnosis, case reporting, and epidemiological investigation. Persons potentially exposed to botulinum toxin should be closely observed, and those with signs of botulism require prompt treatment with antitoxin and supportive care that may include assisted ventilation for weeks or months. Treatment with antitoxin should not be delayed for microbiological testing. PMID- 11209186 TI - Health care 2001: "top 10 trends" in a technology-driven future. PMID- 11209179 TI - Complementary strategies to prevent firearm injury. PMID- 11209187 TI - "Top 10" trends predictions were 100 percent accurate for year 2000. PMID- 11209188 TI - Major new regs coming for patient privacy, security. PMID- 11209189 TI - OSHA ergonomics standard has sweeping requirements. PMID- 11209190 TI - Improving the process for preop antibiotics. PMID- 11209191 TI - How to keep orientees on board. PMID- 11209192 TI - Boston project prepares RNs for OR. PMID- 11209193 TI - Complying with new sedation standard. PMID- 11209194 TI - HIPAA primer for surgery centers. PMID- 11209195 TI - Outpatient surgery doubles. PMID- 11209197 TI - AONE sends message on shortage. PMID- 11209196 TI - Simpler, more productive meetings. PMID- 11209198 TI - Businesses launch assault on errors. PMID- 11209199 TI - Congress finally passes BBA relief! PMID- 11209200 TI - Annual "Top 100" hospital list unveiled--26 federation hospitals included. PMID- 11209201 TI - Representative Marion Berry, D (AR-01). A healthcare legislative update: 107th Congress preview. PMID- 11209202 TI - Universal Health Services, Inc. PMID- 11209203 TI - 2001 post-election update. 107th Congress brings new health views to the U.S. Senate. PMID- 11209204 TI - Slicing through Internet data. PMID- 11209205 TI - Center takes data tracking to heart. PMID- 11209206 TI - Doctors sound off on I.T. concerns. PMID- 11209207 TI - Juggling skills a must for health care CSOs. PMID- 11209208 TI - A vendor consolidation scorecard for 2000. PMID- 11209209 TI - Retaining staff is key to success. PMID- 11209210 TI - New M&R benchmarks reveal HMO industry trends. PMID- 11209211 TI - Know your costs? Check these medical practice data for comparison. PMID- 11209212 TI - Are hospitals losing faith in managed care? PMID- 11209213 TI - Unlike hospitals, IPAs still rely heavily on capitation revenue. PMID- 11209214 TI - Utilization data confirm positive influence of capitation. PMID- 11209215 TI - Three surefire ways to cut your pharmacy costs. PMID- 11209216 TI - Harvard Pilgrim's financial distress holds lessons for other risk-bearing groups. AB - What lessons can be learned from the financial collapse and rehabilitation of Harvard Pilgrim Health Plan? One managed care expert says many of the factors that hurt Harvard Pilgrim can be seen in other plans across the nation. PMID- 11209217 TI - Make sure your stop-loss coverage can still do the job. AB - Is your stop-loss coverage still adequate? Here are the changes in conditions you need to evaluate to be sure you're still well covered. PMID- 11209218 TI - Analysis confirms pharmacy driving health care cost hikes. AB - Data insight: What drove last year's 6.6% increase in overall healthcare costs? Pharmacy cost increases. An analysis by the Center for Studying Health System Change also confirms that insurer premium increases are outstripping cost increases. PMID- 11209219 TI - IPAs improve utilization control with blended RVU/contact cap plan. AB - A Phoenix healthcare consultant has devised a way of helping specialists succeed financially under capitation contracts by combining cap payments with changes in internal RVU rates. PMID- 11209220 TI - [Open aortic valvuloplasty in surgical treatment of associated heart diseases]. AB - The article presents indications to surgical correction of aortal stenosis and its variants in patients with rheumatic diseases combined with a lesion of other valves of the heart. The possibility to fulfill valve-saving plastic operations on the stenosed aortal valve was shown in 110 operations. The results obtained proved advantages of plastic operations over prostheses of the stenosed aortas without calcinosis universalis. Such operations allowed the intrahospital lethality to be considerably decreased. In later terms only two patients needed prostheses of the valve. The functional class was improved in the overwhelming majority of the patients. PMID- 11209221 TI - [Causes of exploratory thoracotomies in lung cancer]. AB - Exploratory thoracotomies were studied in 80 patients with inoperable lung cancer. The X-ray and computed tomography findings were analyzed retrospectively. The main causes of inoperability of lung cancer were determined. The authors consider that CT findings are of greater importance as compared with the routine X-ray examination and linear tomography for determining the lung cancer operability. PMID- 11209222 TI - [Surgical correction of blood and lymph circulation in liver cirrhosis]. AB - After modeling cirrhosis of the liver in experimental dogs the gastroesophagolienal hemo- and lymphocirculation and that of the greater omentum were transferred into the system of the vena cava inferior, the mesenterial outflow being preserved through the liver. The dynamic observation of the experimental animals has shown the intervention performed to be valid. In 6 patients the gastroesophagolienal circulation and that of the greater omentum were transferred into the system of the vena cava inferior. The proposed method of surgical correction leads to lower portal pressure, to saved hepatopetal blood flow along the portal vein. The reestablished absorbing capacity of the greater omentum and the developed collateral lymph circulation decrease the transudation of the lymph into the abdominal cavity and increase its reabsorption. PMID- 11209223 TI - [Ultrasound study and computerized tomography in the diagnosis of choledocholithiasis]. AB - A comparative analysis of the results of using the ultrasonic investigation and computed tomography in differential diagnosis of jaundice was made in 205 patients. The reliability of USI in diagnosis of cholelithiasis was 54.3%, and that of standard CT was 55.9%. The authors have developed and used computed tomocholangiography (direct and indirect) in 187 patients with pronounced bilirubinemia. Indirect tomocholangiography was used in patients with bilirubinemia not more than 157 mkm/l. Contrasted main bile ducts were noted in 95% of the patients. When the content of bilirubin in blood plasma was higher than the figures shown, the authors used the direct contrast of the bile ducts in combination with computed tomography. When using more perfect X-ray devices (CT) with the greater resolving power for diagnosis in jaundice patients, it was possible to get the overwhelming information about the state of the bile ducts. PMID- 11209224 TI - [Splanchnic hemodynamics in acute cholecystitis and mechanical jaundice]. AB - The authors analyze results of the investigation of hemodynamics in the abdominal cavity vessels by the method of duplex scanning in 30 patients with acute cholecystitis, in 30 patients with mechanical jaundice and cholelithiasis and in 30 healthy subjects. It was found that these patients had less blood flow along the upper mesenterial artery and the portal vein. As a compensation the blood flow increased along the hepatic artery. PMID- 11209225 TI - [Surgical treatment of rectal cancer in middle-aged and elderly patients]. AB - This article presents results of surgical treatment of 439 patients with cancer of the rectum, including 310 (70.6%) patients older than 60. The transabdominoperineal extirpation of the rectum was made in 48.1% of the elderly and senile patients, the anterior (transabdominal) resection--in 33.6%, Gartman's operation--in 12.6%, transanal excision of the tumor--in 11 patients. Lethal outcomes after the surgical interventions was 4.8%. PMID- 11209226 TI - [Use of leukocytic suspension in the treatment of diffuse peritonitis]. AB - Immunocorrection by means of transfusions of donor leukocytes was performed in 64 patients. Transfusions of the leukocytic suspensions in short courses (2-3 transfusions to one patient or 300-500 ml per a course) during the first three days after operation allowed the immune status of organism to be improved and increased the effectiveness of the antibacterial and infusion-detoxication therapy. The greatest medical effect was obtained when using the leukosuspension from donors with natural high (from 1:160 and higher) titers of antibodies to E. coli. PMID- 11209227 TI - [Diagnosis of heart contusions in patients with multiple trauma of the chest]. AB - A complex investigation of effectiveness of different methods of detection of heart contusion in patients with combined traumas of the chest allowed detailed elucidation of the criteria of diagnostics of heart contusions by means of electrocardiography, integral rheography of the body, ultrasonography, enzyme diagnostics. A comparative analysis has shown that none of the available now methods can be taken as absolute. The complex use of these methods only can make the maximum objective diagnosis of heart contusion. This approach allowed the authors to make the amount of diagnostic errors 18% less in patients with a combined trauma of the chest and thus to improve the results of treatment. PMID- 11209228 TI - [Possibilities and results of organ-saving surgery in injuries of the spleen]. AB - An analysis of 218 patients with spleen traumas treated surgically has been made. The organ-saving operations were made in 70 patients with a laser scalpel. The absolute and relative indications for such operations were determined. Complications and lethal outcomes in the early postoperative period in patients with the preserved spleen and after splenectomy were 21.1% and 12.9%, 30% and 13% correspondingly. PMID- 11209229 TI - [Immediate results of the treatment of gunshot wounds of the large intestine]. AB - Under analysis were the strategy and results of treatment of 1264 patients with gunshot wounds of the colon. Isolated injuries of the colon were noted in 32.3% of the patients, 67.7% of the patients had combined wounds. The overall lethality was 12.1%. The methods of surgery were chosen depending on the character of the wounds. PMID- 11209230 TI - [The problem of posttraumatic fat embolism]. AB - The article is devoted to the problem of fat embolism. In 63 patients with combined and isolated traumas the maximum frequency of fat embolism was diagnosed in the investigation of blood serum from the femoral artery. It can be supposed that no isolated injury of the lesser circulation circuit can occur in fat embolism. An investigation of the venous-arterial difference of fat globulemia has shown the main role of the so-called theory of shunting for fat embolism to be doubtful. PMID- 11209231 TI - [The effectiveness of auricular micro-needle acupuncture in the early postoperative period under conditions of day surgical unit]. AB - The authors have developed a method of auricular microneedle analgesia--setting the microneedles in the area of the auricle floor for the period of up to 5 days which could reduce the pain syndrome. PMID- 11209232 TI - [Use of an artificial carrier of oxygen on the base of modified hemoglobin in patients with gastroduodenal hemorrhage]. AB - Infusions of Helenpole used in 23 patients allowed for a short time to stabilize hemodynamics and to considerably improve the gas-transporting function of blood. The best curative effect in patients with hemorrhagic shock was obtained by means of intravenous jet infusions of the medicine, after stabilization of the hemodynamic indices with the help of an intravenous dropper (80-90 drops/min). The dose of the 1% solution of the medicine was 25-30 ml/kg of the patient's body weight. PMID- 11209233 TI - [Effects of methods of freezing and thawing of blood plasma on the activity of procoagulants and antithrombin-III]. AB - The authors investigated the activity of procoagulants and antithrombin-III after freezing and thawing of blood plasma by different methods. It was shown that quick freezing and thawing using special apparatuses best of all preserved the coagulative properties of the plasma. The medical efficiency of quick-frozen plasma was shown to depend on the method of freezing and thawing. PMID- 11209234 TI - [Photo-hemo-correction in the complex treatment of patients with obliterating atherosclerosis of the arteries of the lower limbs]. AB - Based on the assessment of clinical efficiency of the intravascular and percutaneous photomodification of blood with a helium-neon laser in 170 patients the authors have shown that it is expedient to include the photohemocorrection in the medical programs for the I-III degree ischemia. PMID- 11209235 TI - [A method of isolation and preparation of the radial artery for direct revascularization of the myocardium]. AB - The authors describe a technique of the isolation, preparation and use of the radial artery for the aortocoronary shunting for ischemic heart disease. The method is anatomically valid and approbated in 300 operations on the open heart. Safety and efficiency of using the radial artery is due to its not traumatic isolation, original preparing for shunting and medicamental prevention of its spasm. PMID- 11209236 TI - [Method of the anterior resection of the rectum with formation of invagination colorectal anastomosis]. AB - In order to prevent complications associated with incompetent sutures of the anastomosis in performing frontal resection of the rectum the invaginational immersion of the one-row catgut interintestinal anastomosisis was performed into the lumen of the inferioampullar portion of the rectum to a depth of 15-20 mm by means of traction by a plastic ring which was fixed when applying the anastomosis on the side of its lumen to the suture knots. The method was used in 12 patients without complications due to incompetence of the anastomosis sutures. PMID- 11209237 TI - [Characteristics of the diagnosis of purulent pyelonephritis]. AB - Results of diagnosing pyelonephritis in 106 patients using ultrasonography, CT and thermovision were analyzed. Purulent pyelonephritis (PP) was diagnosed in 57 patients, serous pyelonephritis--in 49 patients. The sensitivity of ultrasonography in the diagnosing of PP was more than 80%, that of CT--90%. The methods used allowed the 100% improvement of the differential diagnosis of renal abscess, apostematous nephritis and pyonephrosis. The greatest problems were met in the diagnosis of renal carbuncle which was detected in 50% of cases by ultrasonography and in 54% of patients by CT. The minimum sizes of the destruction focus when the diagnosis could be reliable were 2 cm for ultrasonography and 1.5 cm for CT. Only using the findings of CT could diagnose emphysematous pyelonephritis. Thermovision could not find any definite criteria of PP. The timely diagnosis of PP allowed the organ-saving operations to be fulfilled in the overwhelming amount of the patients. Positive results of the treatment using the above mentioned diagnostic methods were obtained in 98.8% of the patients. PMID- 11209238 TI - [Active drainage of the abdominal cavity in diffuse purulent peritonitis]. AB - The method of active drainage of the abdominal cavity and of the gastrointestinal tract lumen for acute peritonitis described by the author is based on the intraabdominal cyclic compression-decompression method of action on the organs and tissues of the abdominal cavity using 2-4 hermetically sealed rubber gloves distended with the help of a respiratory system in the uninterrupted regimen of work during 2-3 days. The method was used in 24 patients. Six patients died. No complications due to the method of treatment were observed. PMID- 11209239 TI - [Injury of the esophagus in closed trauma of the neck]. PMID- 11209240 TI - [Incarcerated congenital diaphragmatic hernia with the background of malformations of the intestine]. PMID- 11209241 TI - [A rare wound of the bladder]. PMID- 11209242 TI - [Apropos of the article by I.A. Eriukhin "Multiple organ dysfunction syndrome". The nature of the concept and the correctness of terminology"]. PMID- 11209243 TI - [Clinical aspects, diagnosis and treatment of odontogenic mediastinitis]. PMID- 11209244 TI - [Acute pancreatitis and bacterial translocation]. PMID- 11209245 TI - [Erast Gavrilovich Salishchev (1851-1901)]. PMID- 11209246 TI - [Bacterial complications after endoscopic procedures in patients with portal hypertension]. PMID- 11209247 TI - [Transitory synovitis of the hip joint in children]. PMID- 11209248 TI - On the job. Does this man need a shrink? PMID- 11209249 TI - [Cryptosporidiosis in the Andean region of Colombia: seroprevalence and recognition of antigens]. AB - The objective of this study was to investigate, for the first time, the seroprevalence of cryptosporidiosis among urban and rural inhabitants in several departments of the Andean region of Colombia. The antigen recognition of Cryptosporidium parvum was also studied with sera. Between June 1996 and October 1998 1,778 serum samples were collected from people selected through convenience sampling. The detection of anti-C. parvum antibodies (IgM, IgA, and IgG) was carried out with enzyme-linked immunosorbent assay, and antigen recognition was done with immunoblotting. A prevalence of 83.3% was found, and the antibody percentages were 72.2% for IgM, 27.7% for IgA, and 27.6% for IgG. Higher seropositivity percentages were found among women, persons less than 30 years old, and residents of rural areas. IgM seroprevalence decreased with age, while IgG and IgA seroprevalences increased with age. These three immunoglobulin isotypes most frequently recognized the antigens from 51 to 69 kDa, which can be considered immunodominant. Of note was the immunoreactivity of IgM and IgA to protein fractions from 12 to 14 kDa and from 42 to 48 kDa, respectively, which could indicate exposure to the parasite. These results indicate that cryptosporidiosis is endemic in the Andean region of Colombia, and that it is possible to attribute many cases of diarrheal syndrome to C. parvum. PMID- 11209250 TI - Nutritional status of children under 5 years of age in three hurricane-affected areas of Honduras. AB - Hurricanes and other natural disasters can produce crop destruction, population displacement, infrastructure damage, and long-term public health consequences that include increased malnutrition among the affected populations. This paper presents the results of anthropometric measurements taken of 295 children under 5 years of age from three regions of Honduras that were affected by Hurricane Mitch, a major storm that struck Central America in the fall of 1998. The children in our study were sampled in three shelters in the capital city of Tegucigalpa; in the resettlement zone of Nueva Choluteca, Choluteca; and in the small urban area of Catacamas, Olancho. Our data indicated that, in comparison to the period before the hurricane, there was an elevated prevalence of wasting in all three of the study areas, and that there were also high levels of underweight in the Tegucigalpa and Nueva Choluteca study areas. There were statistically significant differences between the mean values of malnutrition indicators for Catacamas and those for the Tegucigalpa and Nueva Choluteca settlements. These differences suggest that resettled families were confronting a nutritional crisis in July and August of 1999, some 9 months after the hurricane struck. PMID- 11209251 TI - [Evaluation of the effectiveness of a new vaccine against human leptospirosis in groups at risk]. AB - In order to evaluate the effectiveness of a new vaccine against human leptospirosis, a prospective cohort study was done with persons in the Cuban province of Holguin who were at risk of becoming ill with leptospirosis. The study included 118,018 persons from 15 to 65 years old who were considered to face either permanent or temporary risk. The vaccinated cohort consisted of 101,137 persons. They received two vaccine doses, 6 weeks apart, of 0.50 mL via deep intramuscular injection into the deltoid muscle of the nondominant arm. The unvaccinated cohort consisted of 16,881 persons. Epidemiological surveillance began 21 days after the application of the second vaccine dose and continued for 1 year. The same criteria for suspected and confirmed cases were maintained throughout the study period. At the end of the surveillance period effectiveness was calculated as being higher than 97%. It is estimated that the vaccination program prevented eight out of ten cases that would have otherwise occurred. Vaccine reactogenicity was also measured in a subsample of 1,500 persons between 15 and 65 years old. The observed symptomatology was low. Slight pain at the injection site was the most frequent symptom (25%). The results of the study indicate the usefulness of the vaccine for disease prevention among people at risk, and its use is thus recommended. PMID- 11209252 TI - [History, effects and mechanisms of action of ecstasy (3,4 methylenedioxyamphetamine): review of the literature]. AB - This review focuses on 3,4-methylenedioxymethamphetamine, an illegal drug known as "ecstasy." Ecstasy was introduced in Brazil in 1994. Data are lacking on the epidemiology and usage pattern of the drug in Brazil. However, there is evidence that until now the use of ecstasy has been limited to middle-class or upper middle-class youth, so that most people, including health care professionals, are unfamiliar with the drug. However, ecstasy may be becoming more popular in Brazil, following a pattern seen in North America and Europe. Possible contributing to the drug's popularity is the fact that ecstasy is sold as a pill and is thus extremely easy to use. Ecstasy has a reputation for not being physically dangerous; however, there are many reports of adverse reactions associated with the drug. In addition, it is known that not all pills sold as ecstasy actually contain methylenedioxymethamphetamine. Since there is no quality control for the pills' contents, users never know exactly what they are taking. Thus, although users may perceive the effects of the drug as mostly positive, ecstasy is potentially dangerous. Primary and secondary interventions are needed to prevent the use of ecstasy and the occurrence of adverse reactions. To be effective, these measures must take into consideration the characteristics of the user population and the usage patterns. It is also essential to prepare health professionals for emergency medical interventions in cases of intoxication and complications resulting from the use of ecstasy. PMID- 11209253 TI - The use of socioeconomic factors in mapping tuberculosis risk areas in a city of northeastern Brazil. AB - In Brazil the challenge of meeting the needs of those living in deprived areas has generated discussions on replacing the existing approach to epidemiological surveillance with an integrated public health surveillance system. This new approach would supplant the traditional focus on high-risk individuals with a method for identifying high-risk populations and the areas where these persons live. Given the magnitude of the problem that tuberculosis (TB) poses for Brazil, we chose that disease as an example of how such a new, integrated public health surveillance system could be constructed. We integrated data from several sources with geographic information to create an indicator of tuberculosis risk for Olinda, a city in the Brazilian state of Pernambuco. In order to stratify the urban space in Olinda and to check for an association between the resulting TB risk gradient and the mean incidence of the disease between 1991 and 1996, we applied two different methods: 1) a "social deprivation index" and 2) principal component analysis followed by cluster analysis. Our results showed an association between social deprivation and the occurrence of TB. The results also highlighted priority groups and areas requiring intervention. We recommend follow up that would include treating acid-fast bacilli smear-positive pulmonary TB cases, tracing of these persons' contacts, and monitoring of multidrug-resistant cases, all in coordination with local health services. PMID- 11209254 TI - [Detection of antibodies against Trypanosoma cruzi in Somoto, Nicaragua, using indirect ELISA and IFI on blood samples on filter paper]. AB - We standardized a solid-phase enzyme-linked immunosorbent assay (ELISA) in order to study the presence of Trypanosoma cruzi antibodies in asymptomatic persons who live in an area of Nicaragua endemic for Chagas' disease. The test was standardized to analyze filter-paper blood samples, which are easy to transport. In the first phase of our investigation, ELISA was used to study 18 samples of total serum and 18 eluates of blood from patients with chronic Chagas' disease; 30 samples of serum and 30 eluates of blood from healthy people, used as negative controls; and 14 samples of serum and 14 eluates of blood from patients with cutaneous or visceral leishmaniasis, which were used to study cross-reactions. Both with the total-serum and the blood-eluate samples, the ELISA test provided 100% sensitivity and 90% specificity. Cross-reactions in the patient samples were observed only with visceral leishmaniasis. The second phase of our investigation was a population study that included eight rural communities in the area of Somoto, Nicaragua. Through random sampling, filter-paper blood samples were collected from 2,434 people (1,335 men and 1,099 women) from the communities of Aguas Calientes, El Brocal, La Manzana, Las Playas, Los Canales, Santa Isabel, Santa Rosa, and Santa Teresa. Studied by ELISA and by indirect immunofluorescence (IIF), the samples included 260 found seropositive by ELISA (10.7%), of which 207 were positive according to IIF (8.5%). With both techniques, the majority of seropositives were among women, but the difference between men and women was not statistically significant. There was a high level of agreement between the results obtained with the two techniques. There was an upward trend with age, with 5.4% of those found seropositive by ELISA being persons 10 years of age or younger and 42.7% of those found seropositive being older than 50. The vast majority of the individuals analyzed were asymptomatic. PMID- 11209255 TI - [Methodological aspects of determination of angiotensin-converting enzyme]. PMID- 11209256 TI - [The specificity of lipid metabolism in hereditary arterial hypertension induced by stress]. AB - Studies of lipid metabolites in the plasma and lymph of rats with hereditary arterial hypertension induced by stress (HAHIS) showed decreased plasma and lymph pool of total cholesterol (TC) in comparison with normotensive Wistar rats. In HAHIS animals, TC concentration in the lymph was lower than in the plasma. The concentrations of triglycerides and free fatty acids in the plasma and lymph of hypertensive animals were virtually the same and higher than in normotensive ones. Plasma concentration of malonic dialdehyde (MDA) in HAHIS rats was the same as in Wistar rats, while the lymph concentration of MDA was higher than in Wistar rats. The detected lipid metabolism characteristics reflect its genotypical and phenotypical rearrangement and are a component of the "metabolic syndrome", detected in patients with essential hypertension and animals with spontaneous arterial hypertension. PMID- 11209257 TI - [Biochemical characteristics of liver involvement in patients with antiphospholipid syndrome]. AB - The incidence of hepatitis B and C virus and cytomegalovirus infection is high in patients with the antiphospholipid syndrome (APS). The specific features of virus infection in APS patients are determined by the activity of APS. During clinically manifest stage, the activities of aminotransferases, lactate dehydrogenase (LDH), and alkaline phosphatase increase, while during remission only aspartate aminotransferase and LDH levels remain high, for this latter enzyme high activities of isoenzymes LDH5 and LDH4 being recorded. These data indicate that the pathological process in APS involves not only the liver, but the sinusoidal endothelium as well. This seems to account for some other clinical and laboratory manifestations of APS, such as increased level of circulating immune complexes, dysfunction of physiological anticoagulants, etc. PMID- 11209258 TI - [Retention volume of some steroids during their separation by high performance liquid chromatography]. AB - The volume of retention of corticosterone, hydrocortisone, aldosterone, dexamethasone, cortisone, methylprednisolone, and prednisolone during their separation by high-performance liquid chromatography was evaluated. The studies were performed on a Milichrome microcolumn chromatographer. The order of glucocorticoid release and volume of their retention were under study. Measurement of endogenous and exogenous plasma glucocorticoids is practically important in clinical medicine. Steroid concentrations indicate the pharmacodynamics and pharmacokinetics of exogenous glucocorticoids and their effects on the production of endogenous steroids and reflect the biorhythms of corticosterone and hydrocortisone. PMID- 11209259 TI - [Detection of natural anti-angiotensin converting enzyme antibodies in human serum using immunoenzyme technique ]. AB - Solid-phase enzyme immunoassay (EIA) was developed for detecting natural antibodies to angiotensine-converting enzyme (ACE). Optimal conditions for detecting natural anti-ACE by EIA in the sera of donors and patients with disorders of arterial pressure are selected. The findings indicate that the level of natural anti-ACE is normally constant, while in the patients it is increased in 50% cases. PMID- 11209260 TI - [Chronic leukemias (lecture)]. PMID- 11209261 TI - [The take-up of saturated and polyenic fatty acids by cells: pharmacokinetics, pharmacodynamics and mechanism of fibrate action (review of literature)]. PMID- 11209262 TI - [Prevalence of rheumatoid factor in the healthy population of Moldova Republic]. AB - A total of 1009 normal human sera (524 (51.9%) male and 485 (48.1%) female) were screened for rheumatoid factor (RF). The age of donors varied from 17 to 61 years, mean age 34 was years. The screening was performed by 3 methods with the following antigenic RF substrates: modified human IgG (latex test), Fc fragment of rabbit IgG (Vaaler-Rose test), and their combination (Refa-Dac diagnostic agent). RF with activity of at least 3 IU/ml was detected in 3.1% subjects and with the activity higher than the common diagnostically significant level (20 IU/ml) in 5.58% examinees. RF more often occurs in healthy women than in men, particularly at the age of 17-39 years. PMID- 11209263 TI - [Morphodensitometric evaluation of lymphocytes enzymatic status in pathogenesis of chronic alcoholism]. AB - Activities of succinate dehydrogenase (SDH), alpha-glycerophosphate dehydrogenase (alpha-GPDH), and nonspecific esterase (NE) were studied in blood lymphocytes of healthy men and chronic alcoholics. SDH activity was notably decreased, while the levels of alpha-GPDH and NE were increased in alcoholics. The detected metabolic changes suggest lymphocyte dysfunction and hence, impairment of neuroimmune relationships, which may be the central component in the pathogenesis of chronic alcoholism. PMID- 11209264 TI - [The use of electrochemoluminescent method for detection of cytokines in various media]. AB - Electrochemiluminescent (ECL) method was used for cytokine detection with TAG label (ruthenium(II) tris-bipyridine chelate N-hydroxysuccinimide ester). A quantitative ECL detection of IL-4 and IFN-gamma in physiological fluids and cell culture media is described. The results evidence that ECL is compatible to commercial kits or even more effective. The advantages of ECL are simple procedure, no need in washings, small volume of the assay, wide range of cytokine concentrations, high sensitivity, and good reproducibility. The method can be used in research and clinical laboratories. PMID- 11209265 TI - [Immunomagnetic adsorption of malignant cells (Review of literature)]. PMID- 11209266 TI - [Comparative study of platelets from healthy human donors using light microscopy and flow cytometr "Cobas micros"]. AB - Peripheral blood platelets of 25 normal subjects were examined by optic microscopy and flow cytometry. Blood was collected routinely into tubes for Cobas Micros flow scintillator with EDTA anticoagulant. Smears were made as a monolayer and stained by May-Grunwald's method in our modification. Morphologically, 5 classes of platelets were distinguished under optic microscope: young, mature, old, macroplatelets, and irritated forms. The percentage of each class was estimated (i.e., normal platelet formula was determined). Comparison of platelet parameters obtained on a flow cytometer and optic microscopy data for subjects with high percentage of large platelets showed increased mean volume of platelets (MPV) and width of platelet volume (PDW). The curve reflecting platelet distribution by volume in these donors was characterized by strong inclination to the right and a flat plateau. PMID- 11209267 TI - [Automation and organization of technological process of urinalysis]. AB - Results of introduction into practice of a working model of industrial technology of laboratory studies and KONE Specific Supra and Miditron M devices are shown as exemplified by clinical analysis of the urine. This technology helps standardize all stages and operations, improves the efficiency of quality control of laboratory studies, rationally organizes the work at all stages of the process, creates a system for permanent improvement of the efficiency of investigations at the preanalytical, analytical, and postanalytical stages of technological process of laboratory studies. As a result of introduction of this technology into laboratory practice, violations of quality criteria of clinical urinalysis decreased from 15 to 8% at the preanalytical stage and from 6 to 3% at the analytical stage. Automation of the analysis decreased the need in reagents 3 fold and improved the productivity at the analytical stage 4-fold. PMID- 11209268 TI - [An achievements of laboratory medicine for clinical practice. New tests and technologies (about the conference in Ufa)]. PMID- 11209269 TI - Marketplace. Demographics, economic cycles conspire to inflate health costs for years ahead. PMID- 11209270 TI - Perspectives. Congress in 2000 gets low marks on health, but shows signs of getting serious. PMID- 11209271 TI - Wandering OSHA's Web site. PMID- 11209272 TI - Follow the money. AMA's long-delayed annual report offers unsettling news on physicians' incomes. PMID- 11209273 TI - JCAHO's new tell-all. Standards require that patients know about below-par care. PMID- 11209274 TI - Hospital in custody fight. Florida officials may take facility away from parent company to keep it open. PMID- 11209275 TI - Outlook 2001. Depending on whom you work for, there's good news and bad news. PMID- 11209276 TI - HIPAA will be no holiday. Experts say exhaustive rules may require significant cultural and administrative changes. PMID- 11209277 TI - Dialing up high-tech medicine. L.A. university opens doors to its third telemedicine center to serve urban patients. PMID- 11209279 TI - Learning a valuable lesson. Teaching hospitals still beating their nonteaching counterparts in Medicare margins. PMID- 11209278 TI - Investors demand more analysis. Credit-rating agencies to issue quarterly reports on hospital financial data; S&P to charge fees. PMID- 11209280 TI - Mealtimes are a big deal. PMID- 11209281 TI - Therapy in bloom. PMID- 11209282 TI - Communicating with our elderly. PMID- 11209283 TI - Affordable assisted living. PMID- 11209284 TI - We cannot get there from here. PMID- 11209285 TI - More than kid stuff. PMID- 11209287 TI - How you gonna keep 'em down on the farm? Make the farm integral to their lives, that's how! PMID- 11209286 TI - New Rx for psychoses in Alzheimer's, Parkinson's. PMID- 11209288 TI - A touch of the Orient. Horticulturist brings far eastern beauty to the west. PMID- 11209289 TI - Television documentaries lifting hospital, medical center profiles. AB - The nation's hospitals and medical centers are enjoying the legacy of TV audiences' addiction to medical dramas. Cable television has met the challenge with documentary coverage of real live hospitals. The medium offers many benefits and few disadvantages for those marketing managers with the courage to welcome camera crews. Lynn Hopkins Cantwell is director of public relations and marketing for Children's National Medical Center, Washington, D.C., which was covered in a seven-instrument "Lifeline" documentary for the Discovery Channel. James G. Gosky is director of communications for The MetroHealth System, Cleveland, which was the subject of two installments of "Trauma: Life in th ER," produced for the Learning Channel. These marketing pros describe the myriad details they faced when their respective hospitals went "on camera." Among the key factors were good communications with all constituents, attention to detail, and follow-up. PMID- 11209290 TI - Facts about falls inspire safety program at St. Marys. Wisconsin hospital collaborates with community agencies. AB - In cooperation with senior citizen and health care organizations, St. Mary's Hospital, Madison, Wisc., developed a multi-faceted campaign to raise awareness about accident prevention among older persons. The campaign won recognition from professional peers. PMID- 11209291 TI - St. Peter's reclaims its identity in the face of rapid growth. Two-year process results in new name. AB - A 130-year-old, well-respected Albany, N.Y., hospital, St. Peter's, experienced growing pains as it became a system comprising 25 entities. We describe a branding initiative carefully designed to identify the new health care system with the "old friend." PMID- 11209292 TI - M.D. Anderson Network newsletter builds bonds with patients, survivors. AB - Network, the quarterly newsletter of The University of Texas M.D. Anderson Cancer Center, Houston, builds relationships. Created in 1985 to "empower cancer survivors in the effort to take back control of their lives," it proves its worth in a recent readership survey. PMID- 11209293 TI - Finding a larger newsletter audience. For New York Methodist, new approach is worthwhile. AB - New York Methodist Hospital met the challenges of intense competition in the Brooklyn, N.Y., market by switching its quarterly newsletter to an insert in the local editions of national publications. By so doing, it multiplied distribution tenfold, improved its credibility and freed up staff time for other projects. PMID- 11209294 TI - A good communications plan can defuse crisis situations. AB - Community Health Partners, Lorain, Ohio, met the challenge of two nurses' strikes with comprehensive internal communications and conscientious media monitoring. PMID- 11209296 TI - Cleveland Clinic Web site promotes status, provides helpful information. AB - Publisher Donald E.L. Johnson writes about The Cleveland Clinic Foundation's Web site that both promotes its status as a leading international group practice and medical center and gives patients access to useful medical and health care information. PMID- 11209295 TI - Where health care falls short. Tips on meeting the expectations of women. AB - The experts tell us how to adapt some basic marketing techniques and create new approaches in order to reach this influential market. PMID- 11209297 TI - Low-key marketing--Craig Hospital. Consistent focus on the patient's healing. AB - Craig Hospital, in suburban Denver, was pushed into the limelight when survivors of the Columbine High School shootings were patients for rehabilitation. But high profile cases are treated the same as all others by this world-renowned traumatic brain and spinal cord injury center: the well-being and recovery of the patient is never compromised for the sake of publicity. Ongoing marketing practices are decidedly low-key. PMID- 11209298 TI - Role reversal. The government is reviewing the boundaries between professionals working in the NHS. PMID- 11209299 TI - New look nursing. Three trusts are pioneering a scheme to end the distinction between doctors and nurses. PMID- 11209300 TI - Scots set to clarify law on PVS patients. PMID- 11209301 TI - Millennium nurse. PMID- 11209302 TI - International solutions. PMID- 11209303 TI - Exchange of life. PMID- 11209304 TI - Brown's big idea. PMID- 11209305 TI - Night and day. PMID- 11209306 TI - Trusts: we're getting better. The NHS Confederation is encouraging managers to make good employment practice a priority. PMID- 11209307 TI - Research funding. AB - The RCN Research and Development Co-ordinating Centre is striving to become the source of information on funding opportunities for nurses. PMID- 11209308 TI - The school bullying problem. AB - Research into school bullying has, to date, predominantly focused on prevalence and intervention programmes. This article reviews some of this previous work and goes on to explore and discuss the holistic management of bullying, and outlines the importance of the role of the school nurse. PMID- 11209309 TI - Developing patient satisfaction questionnaires. AB - Karen Collins provides a practical guide to undertaking a patient satisfaction survey. She outlines the background to patient satisfaction research and highlights some of the main issues surrounding patient satisfaction measures. PMID- 11209310 TI - Advocacy in nursing. AB - The role of nurse as advocate is fraught with potential dangers, for both the patient and the nurse. Owen Bennett argues that until there is a universally accepted definition, this will continue to be the case. PMID- 11209311 TI - Changing trends in the laboratory diagnosis of gastroenteritic infections. AB - The micro-organisms responsible for causing gastroenteritis have changed over the last few decades. This article chronicles those changes and describes the laboratory tests devised to improve diagnosis. PMID- 11209312 TI - Coeliac disease. AB - The classic gastrointestinal symptoms of coeliac disease are relatively well known. Alison Sullivan describes their management, emphasising the importance of keeping to an appropriate diet if a range of co-existing and associated diseases are to be avoided. PMID- 11209313 TI - Care of elderly skin. PMID- 11209314 TI - Dealing with complaints. PMID- 11209315 TI - Nursing in a different way. PMID- 11209316 TI - Finding literature. PMID- 11209317 TI - Protection money. PMID- 11209318 TI - Getting to know you. PMID- 11209319 TI - Staying power. PMID- 11209320 TI - A long way from home. PMID- 11209321 TI - Inclusion zone. PMID- 11209322 TI - Home economics. PMID- 11209323 TI - Stick up for me. PMID- 11209324 TI - A strong nursing presence in the Euro-corridors of power. PMID- 11209325 TI - A life in the day of.... PMID- 11209326 TI - No place for poaching. PMID- 11209327 TI - The diversity and complexity of ENB course curricula. PMID- 11209328 TI - Revisiting the concepts of community care and community health nursing. AB - As care moves away from hospital settings, continual re-evaluation of community nursing and health care is essential for the wellbeing of patients. With the approach of the year 2000, Jean Clarke examines World Health Organization objectives, particularly in light of the Health for All (1998) policy. PMID- 11209329 TI - Type 2 diabetes. AB - Type 2 diabetes can cause blindness, kidney failure and peripheral neuropathy, and is associated with premature death. Mary MacKinnon reviews this complex major disease and describes new treatments that are due to be licensed in the UK in the coming year. PMID- 11209330 TI - Injection techniques and safety. PMID- 11209331 TI - Preparing for the future. PMID- 11209332 TI - Quality, availability, access--the key to good placements. PMID- 11209333 TI - What's in a name? PMID- 11209335 TI - Quality through equality. PMID- 11209334 TI - Nursing students should go to jail. PMID- 11209336 TI - Care of the community. PMID- 11209337 TI - Profile: Barry Adams in his own words. PMID- 11209338 TI - Barry Adams--the saga continues. PMID- 11209339 TI - "A battle for the very profession itself". PMID- 11209340 TI - Outpatient ... and out of luck? PMID- 11209342 TI - Beyond outrage. PMID- 11209341 TI - The possible dream. PMID- 11209343 TI - Raising voices, protecting patients. PMID- 11209345 TI - Profile: Pam Douglas nurse and whistleblower. PMID- 11209344 TI - Stop! ... in the name of quality care. PMID- 11209346 TI - Reaching new heights. PMID- 11209347 TI - Break point. PMID- 11209348 TI - Night terrors. PMID- 11209349 TI - Brought to heal. PMID- 11209350 TI - The art of listening. PMID- 11209351 TI - Cancer lottery. PMID- 11209352 TI - Pension plan. PMID- 11209354 TI - Auditing deaths from epilepsy. PMID- 11209353 TI - Going public. PMID- 11209355 TI - Bowel preparation for rectal and colonic investigation. AB - BACKGROUND: Nurses need to have a clear understanding of the reasons for effective bowel preparation for patients undergoing imaging of the rectum and colon. CONCLUSION: Depending on the specific investigation, a variety of effective oral and rectal preparations are available. One of the most important deciding factors in choosing which should be used is patient tolerance. PMID- 11209356 TI - Research, ethics and the data protection legislation. AB - As nursing research becomes more common, so does the issue of whether or not patients should be involved and, if so, to what extent. This article examines how the data protection legislation helps to protect patients, and whether they have the capability to decide to participate, or not. PMID- 11209357 TI - Information and support for people with eczema. AB - Growing concern at the increase in eczema sufferers, has led the National Eczema Society to collaborate with nurses and skincare specialists to produce information and support for sufferers and carers alike, which will enable them to manage their condition better. PMID- 11209359 TI - Getting to grips with business plans, audit and applications. AB - Practice profiles are reflective pieces written by nurses in practice and based on continuing professional development articles. This week Sheila Hobbs discusses article NS10. Brocklehurst N et al (1999) Getting into business: how nurses can make a difference. PMID- 11209358 TI - Larval therapy. AB - Larval therapy--the use of maggots as a form of wound care--has been shown to be an effective and fast way to treat some wounds. This article describes how this method can be used successfully in practice. PMID- 11209360 TI - Jobs for life. PMID- 11209361 TI - Plotting a course. PMID- 11209362 TI - Protocols for stoma care. PMID- 11209363 TI - Rich century, poor results. PMID- 11209364 TI - Cross talk. PMID- 11209365 TI - Every man for himself. PMID- 11209366 TI - Simply the best. Managers who get your vote. PMID- 11209367 TI - Future issue. Local employment policies must be women-friendly. PMID- 11209368 TI - It's over to you. PMID- 11209369 TI - Transplant opt out debate goes on. PMID- 11209370 TI - Dignity: a study of pre-operative patients. AB - When being prepared for surgery, pre-operative patients undergo a series of processes and procedures which can compromise their dignity. This article examines this phenomenon and suggests ways to reduce it effects. PMID- 11209371 TI - Guidelines for administering blood and blood components. AB - The Serious Hazards of Transfusion (SHOT) scheme has revealed that many patients have received incorrect blood or blood component. This article reports new national guidelines for ordering, administering and managing blood, blood components and blood transfusion. PMID- 11209372 TI - Informal carers of people with dementia: the new national carers framework. AB - Carers of people with dementia themselves have to endure heavy physical and emotional burdens. This article examines the government's new strategy Caring About Carers (DoH 1999). PMID- 11209373 TI - Devolution: the effects on health policy. AB - Health policy modernisation and political devolution in the UK creates a challenge for all involved. This article examines this challenge from a nursing perspective. PMID- 11209374 TI - Promoting urinary continence in residential care. PMID- 11209375 TI - Advising patients who have sexually transmitted diseases. PMID- 11209376 TI - Delegation dilemmas. PMID- 11209377 TI - The open approach. PMID- 11209378 TI - Food for thought. PMID- 11209379 TI - Money-go-round. PMID- 11209380 TI - Changing the record. PMID- 11209381 TI - When all your credit runs out. PMID- 11209382 TI - Open door. PMID- 11209383 TI - Stay in ... eat soup. PMID- 11209384 TI - Time is of the essence. It took a 'pushy' woman a month to secure a mammograph privately. PMID- 11209385 TI - The importance of the Care Standards Bill, this year's pay award and support for the pioneering spirit in nursing. PMID- 11209386 TI - Manchester Clinical Supervision Scale. PMID- 11209388 TI - Improving quality of primary health care in a Sudanese dispensary. AB - Nursing in a poverty-stricken war zone means working with poor facilities and coping with different attitudes. Sue Campbell explores how working overseas does not need to curtail the nurse's professional development, and shows how some of the trends followed in the UK can apply abroad. PMID- 11209387 TI - Communication problems of hearing-impaired patients. AB - AIM: The main objective of this national survey was to check the findings of an earlier pilot survey. This had found that patients who had a hearing-impairment and were in hospital were often seriously disadvantaged by their disability. METHOD: The survey was conducted by questionnaire and the sampling frame confined to hearing-impaired patients who had been in hospital during the previous three years. A total of 359 completed and valid questionnaires were returned. RESULTS: The responses confirmed the finding of the pilot survey. They indicated that there were serious shortcomings in the ability of many hospital staff to cope with the problems of hearing-impaired patients. CONCLUSION: Common causes of the problems were identified. The major factor was inadequate training of both nurses and doctors in deaf awareness and the associated communication skills. Other significant factors included patients concealing their disability, pressure of work and poor communication between staff. Appropriate training at all staff levels should eliminate a high proportion of these problems. PMID- 11209389 TI - The 'new genetics' and nursing: what does it have to do with me? AB - Recent developments in genetics mean that this previously specialised subject is now essential knowledge for all nurses. Heather Skirton and Christine Patch describe how fundamental knowledge of the new genetics will enable nurses to help patients through the maze of choices open to them. PMID- 11209390 TI - Nuclear medicine: will I glow in the dark, nurse? AB - Nursing in nuclear medicine is an unknown field for most nurses. This article sheds light on the impact nuclear medicine can have on patients and on the nursing role in caring for patients undergoing diagnosis and treatment using radioisotopes. PMID- 11209391 TI - Learning to apply infection control policies on the ward. PMID- 11209393 TI - A lesson in the age of litigation. PMID- 11209392 TI - Stoma care nursing. PMID- 11209394 TI - Rewarding experience. PMID- 11209395 TI - Millennium bug. PMID- 11209396 TI - Double helping. PMID- 11209397 TI - Making the beds. PMID- 11209398 TI - Blood lines. PMID- 11209399 TI - Where do the hours go? PMID- 11209400 TI - Protecting the vulnerable. PMID- 11209401 TI - Leaving the dark ages. PMID- 11209402 TI - Good news, but just a start. PMID- 11209403 TI - The policy context. PMID- 11209404 TI - Distance learning for post-registered nursing: the facts. AB - AIM: To explore nurses' perceptions and evaluate the potential of distance learning as a method of teaching for post-registered nurses working in the community. METHOD: The study used open-ended questions in focus groups. Each group consisted of nine students each with an interest in post-registration learning. The interviews were taped and transcribed (n = 18). RESULTS: The respondents saw distance learning as a necessary way of updating their knowledge, as long as the education provided was relevant to their practice. They also saw this method of learning as an opportunity to take responsibility for their own learning. There was a conflict of opinion, however, as some respondents felt the courses to be a flexible way to teach and learn, while others found the courses to be too focussed and not necessarily relevant. CONCLUSION: The study provides an insight into distance learning and what some post-registered nurses perceive to be important factors associated with it as a method of teaching. It suggests that post-registered nurses working in the community will benefit from distance learning as a method of teaching. PMID- 11209405 TI - Assessment and learning in post-registration nurse education. AB - Assessment in nurse education concentrates too much on academic abilities and fails to measure the practical nursing abilities of students. This article argues for a change in emphasis, so that assessment is seen as a part of learning, rather than a series of arbitrary hurdles to be negotiated. PMID- 11209406 TI - Computerised databases in infection control. AB - The use of databases in health care is expanding. Systems are now available specifically designed for the management of infection control information. This article examines the expanding role of such databases and looks at the advantages and disadvantages for nurses. PMID- 11209407 TI - The importance of mouth care in preventing infection. AB - Most patients can benefit from nurses taking an active interest in their oral hygiene. Gladys Xavier describes how effective mouth care can improve a patient's quality of life and prevent serious infections. PMID- 11209408 TI - Nursing the child with gastroenteritis. PMID- 11209409 TI - A right to quality of life. PMID- 11209410 TI - Your input is what counts. PMID- 11209411 TI - Bristol: the courage to question. PMID- 11209412 TI - Back to basics. PMID- 11209413 TI - Making things happen. PMID- 11209414 TI - Men at work. PMID- 11209415 TI - Run away success. PMID- 11209416 TI - Diagnosing Bond, James Bond. PMID- 11209417 TI - A private view. PMID- 11209418 TI - 1999 report into perioperative deaths: extremes of age. PMID- 11209419 TI - Spiritual care in nursing: a systematic approach. AB - Ian Govier suggests that patients will benefit if nurses adopt a systematic approach to assessing spiritual needs. However, it may be necessary to evaluate personal spirituality before applying this approach. PMID- 11209420 TI - Are nursing theories holistic? AB - Nursing theories, while claiming to present models of holistic nursing care, do not deal adequately with human spirituality. This article reviews several nursing theories to find out which of them incorporate holism, and, if they do, whether the theorist's definition of holism includes spirituality. PMID- 11209421 TI - Establishing a mental health liaison nurse service: lessons for the future. AB - Mental health liaison nursing teams are developing across the UK with a diverse range of roles and functions. This article provides a description of the development of one such service in a large hospital in outer London and an insight into some of the key factors for success when setting up such a service. PMID- 11209422 TI - The principles and practice of child protection. AB - Nurses working with children might find themselves exposed to issues of child abuse. Sharon Stower discusses how to recognise child abuse, the legislation that exists to protect children and the action available to healthcare staff in cases where abuse of a child is suspected. PMID- 11209423 TI - Improving communication when giving bad news. PMID- 11209424 TI - Travellers' checks. PMID- 11209425 TI - Out of the public glare. PMID- 11209426 TI - Delivering the goods. PMID- 11209428 TI - Prescribing: the challenge. PMID- 11209427 TI - 2000--faster, fairer and convenient. PMID- 11209429 TI - Stretching new wings. PMID- 11209430 TI - To prescribe or not to prescribe. PMID- 11209431 TI - For the record. PMID- 11209432 TI - Waving not drowning. PMID- 11209433 TI - Standing her ground. PMID- 11209434 TI - What's it all about? PMID- 11209435 TI - Across the great divide. PMID- 11209436 TI - Research is every nurse's business. PMID- 11209437 TI - Factors affecting the decision to place a relative with dementia into residential care. AB - AIM: To find out the reasons why carers might decide that they could not continue caring for a relative with dementia at home. METHOD: Semi-structured interviews with carers of relatives who have dementia, before placing their relative into residential care and then again four months after that placement. n = 4. RESULTS: Wandering, aggression, incontinence and physical dependency in people who have dementia are factors that might lead carers to consider placing their relative into residential care; stress associated with Christmas can be another influencing factor. CONCLUSION: Carers looking after a relative who has dementia would benefit if the relative was provided with increased day care and home respite sitting services; services should be increased at Christmas; and support staff should be knowledgeable about the specific needs of people who have dementia and their carers. PMID- 11209438 TI - Evidence-based practice: demolishing some myths. AB - Most nurses base their practice on evidence produced by research. This article examines alternative ways of working and demolishes commonly held nursing myths in the process. PMID- 11209439 TI - Please help! I'm newly qualified. AB - Newly qualified nurses often think they have been thrown in at the deep end. This article examines the reasons why, and looks at how preceptorship can help. PMID- 11209440 TI - Eczema. AB - Eczema is a multifactorial disease that needs a combination of therapies to improve the quality of life for those suffering its symptoms. This article shows how to recognise the different types of eczema, details possible triggers and gives treatment options. PMID- 11209441 TI - Understanding genetics and disease. PMID- 11209443 TI - Using the Internet. PMID- 11209442 TI - Nursing in a secure health setting. PMID- 11209444 TI - Is the healthcare workforce a barrier to cost containment? PMID- 11209445 TI - Is the healthcare workforce a barrier to cost containment? PMID- 11209446 TI - Is the healthcare workforce a barrier to cost containment? PMID- 11209447 TI - Is the healthcare workforce a barrier to cost containment? PMID- 11209448 TI - Indirect cost of ischemic heart disease to employers. AB - BACKGROUND: The management of healthcare programs by employers requires accurate information about the indirect and direct costs of important chronic diseases. OBJECTIVE: To determine the indirect costs of ischemic heart disease from the perspective of the employer in private industry in the United States. DESIGN: Indirect cost of illness analysis using the human capital approach, taking the perspective of the employer rather than that of society. METHODS: Ischemic heart disease was identified in a proprietary claims database of 3.1 million insured persons using an algorithm based on administrative codes. Economic data were derived from the Bureau of Labor Statistics, the Employment Management Association, and published sources. Work-loss data were taken from the National Center for Health Statistics' Health Interview Survey. The indirect cost was calculated as the sum of the costs due to morbidity and mortality. From the perspective of the employer, morbidity costs come from lost productivity, idle assets, and nonwage factors resulting from absenteeism and mortality costs are expenditures for replacing and retraining workers. This differs from calculations from the societal perspective, in which indirect costs are the value of an individual's lost income--both current and potential. RESULTS: The total indirect cost of ischemic heart disease to employers in private industry was $182.74 per enrollee. Ninety-five percent of the indirect cost was the consequence of work loss due to morbidity rather than of mortality costs. CONCLUSION: From the perspective of the employer, the indirect cost of ischemic heart disease is overwhelmingly due to morbidity costs. PMID- 11209449 TI - Disenrollment from Medicare HMOs. AB - BACKGROUND: Since the program's inception, there has been great interest in determining whether beneficiaries who enter and subsequently leave Medicare health maintenance organizations (HMOs) are more or less costly than those remaining in fee-for-service (FFS) Medicare. OBJECTIVES: To examine whether relatively high-cost beneficiaries disenroll from Medicare HMOs (disenrollment bias) and whether disenrollment bias varies by Medicare HMO market characteristics. In addition, we compare rates of surgical procedures and hospitalizations for ambulatory care-sensitive conditions for disenrollees and continuing FFS beneficiaries. DESIGN: Cross-sectional analysis of 1994 Medicare data. PARTICIPANTS AND METHODS: Medicare beneficiaries were first sampled from the 124 counties with at least 1000 Medicare HMO enrollees. From this pool, HMO disenrollees and a sample of continuing FFS beneficiaries were drawn. The FFS beneficiaries were assigned dates of "pseudodisenrollment." Expenditures and inpatient service use were compared for 6 months after disenrollment or pseudodisenrollment. RESULTS: The HMO disenrollees were no more likely than the continuing FFS beneficiaries to have positive total expenditures (Part A plus Part B) or Part B expenditures in the first 6 months after disenrollment. However, disenrollees were more likely to have Part A expenditures. Among beneficiaries with spending, disenrollees had higher total and Part B expenditures than continuing FFS beneficiaries. Moreover, the disparity in total and Part B spending between disenrollees and continuing FFS beneficiaries increased with HMO market penetration. Although Part A spending was higher for disenrollees with spending, it was not sensitive to changes in market share. The HMO disenrollees received more surgical procedures and were hospitalized for more of the ambulatory care-sensitive conditions than the FFS beneficiaries. CONCLUSIONS: On several measures, Medicare HMOs experienced favorable disenrollment relative to continuing FFS beneficiaries as recently as 1994, which increased as HMO market share increased. PMID- 11209450 TI - A comparison of abciximab use in MCO and non-MCO populations. AB - OBJECTIVE: To compare abciximab use in managed care organization (MCO) patients and non-MCO patients undergoing coronary angioplasty, specifically (1) the factors influencing abciximab use, (2) the impact of abciximab on hospital length of stay (LOS), and (3) differences in results in MCO and non-MCO patients. STUDY DESIGN: A retrospective observational study based on data from 87 US hospitals on 13,384 angioplasty patients. PATIENTS AND METHODS: Multivariate analysis was used to control for a wide range of factors (patient demographics, health conditions, admission information, and hospital characteristics) that may influence the likelihood of receiving abciximab and hospital length of stay (LOS). Estimation was conducted via a 2-stage sample selection model. RESULTS: Comorbidities, hospital characteristics, and geographic regions influenced abciximab use in MCO and non-MCO populations. In the non-MCO population, women and minority group members were significantly less likely than white male patients to receive abciximab. Both MCO and non-MCO angioplasty patients who were given abciximab had significantly shorter LOSs (0.66 +/- 0.27 fewer days and 0.87 +/- 0.13 fewer days, respectively) than did patients who were not given this drug. CONCLUSIONS: Access to care for MCO and non-MCO populations differed. Non-MCO women and minorities were less likely than non-MCO white men to receive abciximab, but this difference was not observed in the MCO population. After controlling for high risk indications and selection bias, MCO and non-MCO patients who received abciximab had significantly shorter LOSs than did those who did not receive abciximab. This finding is consistent with the many clinical trials that have observed a reduction in ischemic complications associated with abciximab use. PMID- 11209451 TI - Drugs and the elderly, Part 2: Strategies for improving prescribing in a managed care environment. AB - OBJECTIVE: In part 1 of "Drugs and the Elderly" (December 2000 issue), we reviewed and summarized the vast amount of clinical information on medication use in the elderly for healthcare providers and administrators within managed care. In part 2, we explore the literature on improving prescribing, focusing on those approaches most likely to be useful within a managed care environment. STUDY DESIGN: We reviewed the general literature on medication use in the elderly, focusing on problems and systems approaches to the improvement of medication use in managed care. We created a topic list of general interest to health professionals within managed care and fit the available information into those topics. Thus, the result is an authoritative review rather than a systematic literature review. PATIENTS AND METHODS: Nonquantitative evaluation of the medical literature. RESULTS: We identified several hundred articles describing issues related to medication use in the elderly but only a trivial number that in any way addressed the managed care community directly. There is very little literature on how managed care can best incorporate the lessons of geriatric pharmacology and pharmacy. CONCLUSIONS: There is a paucity of literature for the managed care community of health professionals regarding pharmacology, pharmacoepidemiology, drug utilization review, and other issues related to the use of medication in the elderly population. PMID- 11209452 TI - Ambulatory drug utilization review: opportunities for improved prescription drug use. PMID- 11209453 TI - The employer's perspective. PMID- 11209454 TI - Can administrative database studies inform medication use policy decisions? An application of Occam's razor. PMID- 11209455 TI - Fiberoptic biosensors based on chemiluminescent reactions. AB - The chemiluminescence of luminol in the presence of H2O2 has been exploited to develop fiberoptic biosensors associated with flow injection analysis systems. A chlorophenol sensor was developed based on the ability of certain halophenols to enhance the peroxidase-catalyzed luminol chemiluminescence. Horseradish peroxidase immobilized on a collagen membrane was used. Ten chlorophenols have been tested with this chemiluminescent-based sensor. The lower detection limit was obtained with 4-chloro-3-methylphenol and was equal to 0.01 microM. Electrochemiluminescent-based fiberoptic biosensors for glucose and lactate were also developed using glucose oxidase or lactate oxidase immobilized on polyamide membranes. In the presence of oxidase-generated H2O2, the light emission was triggered electrochemically by means of a glassy carbon electrode polarized at +425 mV vs a platinum pseudo-reference electrode. The detection limits for glucose and lactate were 150 and 60 pmol, respectively, and the dynamic ranges were linear from 150 pmol to 600 nmol and from 60 pmol to 60 nmol, respectively. PMID- 11209456 TI - Development of a chemiluminescent optical fiber immunosensor to detect Streptococcus pneumoniae antipolysaccharide antibodies. AB - A chemiluminescent-based optical fiber immunosensor was developed for the detection of antipneumococcal antibodies. This was accomplished by developing a different chemical procedure utilizing 3-aminopropyl trimethoxysilane and cyanuric chloride to conjugate pneumococcal cell wall polysaccharides to the optical fiber tips, and by improving the sensitivity of the photodetection system. The lowest titer of antipneumococcal antibodies detected by the optical fiber was at a 1:819,200 dilution. The lowest corresponding value by standard enzyme-linked immunosorbent assay was at a 1:98,415 dilution. It was concluded that the optical immunosensor system is an accurate and sensitive method to detect antipneumococcal antibodies and may be an adequate tool to monitor antibodies in specimens such as saliva and urine. PMID- 11209457 TI - Biosensors based on immobilization of biomolecules by electrogenerated polymer films. New perspectives. AB - The concept and potentialities of electrochemical procedures of biomolecule immobilization are described. The entrapment of biomolecules within electropolymerized films consists of the application of an appropriate potential to an electrode soaked in an aqueous solution containing monomer and biomolecules. This method of biosensor construction is compared with a two-step procedure based on the adsorption of an aqueous amphiphilic pyrrole monomer biomolecule mixture on an electrode followed by the electropolymerization of the adsorbed monomers. Another approach is based on the electrogeneration of polymer films functionalized by specific groups allowing subsequently the attachment of biomolecules. The immobilization of biomolecules on these films by covalent binding or noncovalent interactions is described. PMID- 11209458 TI - Immunodetection by quartz crystal microbalance. A new approach for direct detection of rabbit IgG and peroxidase. AB - Biodetection is one of the most important challenges for the twenty-first century: many fields are concerned, mainly environmental and medical. The quartz crystal microbalance (QCM) may offer great possibilities for this purpose: a direct response signal, which characterizes the binding event between a sensitive layer, immobilized onto the surface transducer, and the analyte to be detected, can be obtained. However, for the detection of small biomolecules such as antigens, it is quite difficult to obtain an observable signal that corresponds directly to the binding event. In general, this is owing to the lack of mass sensitivity of the commonly used QCM, with 5- to 10-MHz quartz crystals. For improving this mass sensitivity, a 27-MHz quartz resonator was developed and incorporated in a flow-through microcell. Two biospecies, IgG rabbit and peroxidase enzyme, were studied with this ultra-sensitive QCM in terms of specificity, detection limit, and calibration curve. PMID- 11209459 TI - Microbial sensors of ultraviolet radiation based on recA'::lux fusions. AB - Escherichia coli strains containing plasmid-borne fusions of the recA promoter operator region to the Vibrio fischeri lux genes were previously shown to increase their luminescence in the presence of DNA damage hazards, and thus to be useful for genotoxicant detection. The present study expands previous work by demonstrating and investigating the luminescent response of these strains to ultraviolet radiation. Several genetic variants of the basic recA'::lux design were examined, including a tolC modification of membrane efflux capacity, a chromosomal integration of the recA'::lux fusion, a different lux reporter (Photorhabdus luminescens instead of V. fischeri, allowing the assay to be run at 37 degrees C), and a different host bacterium (Salmonella typhimurium instead of E. coli). Generally, two modifications provided the fastest responses: the use of the S. typhimurium host or the P. luminescens lux reporter. Highest sensitivity, however, was demonstrated in an E. coli strain in which a single copy of the V. fischeri lux fusion was integrated into the bacterial chromosome. PMID- 11209460 TI - Sensitive immunodetection through impedance measurements onto gold functionalized electrodes. AB - This article deals with a direct electrochemical method of detecting antigens using new methods of functionalization of gold electrodes. Based on the reacting ability of gold with sulfhydryl groups, three protocols for the fixation of antibodies have been explored. They are based on either the self-assembling properties of functional thiols bearing long alkyl chains or the possibility of a direct coupling of antibody moieties. Coverage rates as high as 97% can be reached. The analysis of the electrochemical impedance behavior of such layers can lead to a sensitive method for the direct detection of the antibody/antigen interaction. The addition of a redox couple in the tested solution, acting as an amplifier, allowed detection limits for the antigens as low as a few picograms/milliliter to be reached. PMID- 11209461 TI - Biosensor for determination of glucose and sucrose in fruit juices by flow injection analysis. AB - Glucose and sucrose were measured with an amperometric method by using the flow injection analysis technique. A carbon paste electrode with a renewable surface containing glucose oxidase, horseradish peroxidase, and ferrocene was used in combination with the soluble enzymes invertase and mutarotase. The effect of invertase, mutarotase, and ascorbic acid on the electrode response was examined. Glucose and sucrose concentrations were determined with < 3% errors. The proposed method for glucose and sucrose measurements was validated in real samples of fruit juices. The results were also compared with those obtained with the ultraviolet method. PMID- 11209462 TI - Electropolymerization as a versatile route for immobilizing biological species onto surfaces. Application to DNA biochips. AB - Biosensors based on electronic conducting polymers appear particularly well suited to the requirements of modern biological analysis--multi-parametric assays, high information density, and miniaturization. We describe a new methodology for the preparation of addressed DNA matrices. The process includes an electrochemically directed copolymerization of pyrrole and oligonucleotides bearing on their 5' end a pyrrole moiety. The resulting polymer film deposited on the addressed electrode consists of pyrrole chains bearing covalently linked oligonucleotides (ODN). An oligonucleotide array was constructed on a silicon device bearing a matrix of 48 addressable 50 x 50 microns gold microelectrodes. This technology was successfully applied to the genotyping of hepatitis C virus in blood samples. Fluorescence detection results show good sensitivity and a high degree of spatial resolution. In addition, gravimetric studies carried out by the quartz crystal microbalance technique provide quantitative data on the amount of surface-immobilized species. In the case of ODN, it allows discrimination between hybridization and nonspecific adsorption. The need for versatile processes for the immobilization of biological species on surfaces led us to extend our methodology. A biotinylated surface was obtained by coelectropolymerization of pyrrole and biotin-pyrrole monomers. The efficiency for recognition (and consequently immobilization) of R-phycoerythrin-avidin was demonstrated by fluorescence detection. Copolymerization of decreasing ratios of pyrrole-biotin over pyrrole allowed us to obtain a decreasing scale of fluorescence. PMID- 11209463 TI - Comparison between electrochemical and optoelectrochemical impedance measurements for detection of DNA hybridization. AB - The principles of the electrochemical and optoelectrochemical impedance measurements on bare electrolyte/dielectric/semiconductor structures are described. The analysis of the experimental curves allows access to several indications concerning the electrical behavior of such structures. The application of these techniques to follow the electrical behavior of structures modified with two biological systems was investigated. The antibody/antigen recognition did not change the surface charge and, therefore, did not affect the impedance curves with respect to the applied potential. By contrast, the hybridization of two complementary DNA strands on the surface of the structure induced a variation of flat band potential of the semiconductor leading to a shift of impedance curves along the potential axis. This means that it is possible to detect directly the DNA hybridization without the use of labeled probes. The use of light allows the surface to be probed locally. In the future, the application of this technique for direct detection of hybridization on DNA chips should be possible. PMID- 11209464 TI - Sol-gel-derived prussian blue-silicate amperometric glucose biosensor. AB - A new type of inorganic biosensor is introduced. The sensor comprises glucose oxidase enzymes encapsulated in a sol-gel-derived Prussian blue-silicate hybrid network. Glucose is detected by the biocatalytic reduction of oxygen followed by catalytic reduction of hydrogen peroxide by the Prussian blue catalyst. The sol gel silicate entails a rigid encapsulating matrix, the Prussian blue provides chemical catalysis and charge mediation from the reduction site to the supporting electrode, and the enzyme is responsible for the biocatalysis. The feasibility of a dual optical/electrochemical mode of analysis is also demonstrated. PMID- 11209465 TI - Amperometric biosensors based on microflow injection system. AB - Novel electrochemical cells based on a microflow system combined with amperometric enzyme electrodes were developed and served for quantitative determination of various compounds, such as organophosphates and lactose. The resulting biosensors are selective and efficient owing to immobilization of the sensing elements on the electrodes. The sensors are easy to operate, and the procedures are rapid, accurate, reproducible, and inexpensive, requiring neither special skills and training nor complicated instrumentation. The use of a microflow cell ensures the continuous flux of a new substrate, thus preventing the accumulation or adsorption of products to the electrode. Miniaturization of the sensor has two main advantages: (1) it is easy to carry and therefore can be used outdoors as well, and (2) it allows working with low volumes of compounds and reagents, which is highly important when dealing with hazardous compounds. PMID- 11209467 TI - [The developing risks of the allergic child]. AB - 6% of infants are allergic to egg. 50% of them are at risk of becoming sensitive to pneumoallergens and of whom 50% develop asthma. These evolutionary risks which are the allergy "course" of the child may be avoided by a precise interrogation which is orientated towards detection by in vitro tests of F x 5 for foods and Phadiatop for pneumoallergens. The responsible allergens may themselves be shown by skin tests, measurement of specific IgE by CAP-RAST made by UNICAP. PMID- 11209466 TI - Quenching of cascade reaction between triplet and photochrome probes with nitroxide radicals. A novel labeling method in study of membranes and surface systems. AB - We proposed a new method for the study of molecular dynamics and fluidity of the living and model biomembranes and surface systems. The method is based on the measurements of the sensitized photoisomerization kinetics of a photochrome probe. The cascade triplet cis-trans photoisomerization of the excited stilbene derivative sensitized with the excited triplet Erythrosin B has been studied in a model liposome membrane. The photoisomerization reaction is depressed with nitroxide radicals quenching the excited triplet state of the sensitizer. The enhanced fluorescence polarization of the stilbene probe incorporated into liposome membranes indicates that the stilbene molecules are squeezed in a relatively viscous media of the phospholipids. Calibration of the "triple" cascade system is based on a previously proposed method that allows the measurement of the product of the quenching rate constant and the sensitizer's triplet lifetime, as well as the quantitative detection of the nitroxide radicals in the vicinity of the membrane surface. The experiment was conducted using the constant-illumination fluorescence technique. Sensitivity of the method using a standard commercial spectrofluorimeter is about 10(-12) mol of fluorescence molecules per sample and can be improved using an advanced fluorescence technique. The minimal local concentration of nitroxide radicals or any other quenchers being detected is about 10(-5) M. This method enables the investigation of any chemical and biological surface processes of microscopic scale when the minimal volume is about 10(-3) microL or less. PMID- 11209468 TI - [Current childhood food allergies]. AB - Changes of dietary habits, new food technology, international meals and increasing consumption of exotic food has changed the repartition of food allergens. Some food allergens are worrisome and symptoms severe (peanut and nut butters). Others are new and increase strongly: exotic fruits, sesame, mustard and lupin. Primary prevention include avoidance of such food in high risk infants. Product labeling must be improved. PMID- 11209469 TI - [Infant food allergy: digestive manifestations]. AB - Food allergies are frequent in infants where digestive signs predominate. The symptoms are extremely variable and most often non-specific. The signs may be immediate or delayed. The pathology of eosinophilia seems to be frequent and may occur in all parts of the intestine. Diagnosis will be orientated to skin tests, prick and/or patch, measurement of IgE and search for eosinophils in digestive biopsies. Exclusion diet of the suspect food, followed by reintroduction of the food will give certainty to the diagnosis. PMID- 11209470 TI - [Childhood allergic rhinitis]. AB - Allergic rhinitis is the most common chronic disease in children. This frequency is in strong progress. According to ISAAC' study, it concerns a child (6/7 years) on four and a teenager on two. The seasonal rhinitises are generally well treated. Perennial allergic rhinitises are chronic and often neglected. They are more often complicated or associated to asthma which represents the major evolutionary risk. In a general way, allergic rhinitis are sub-diagnosed and untreated while we have more and more effective therapeutic means. Although allergic rhinitis is not considered as a severe disease, its echo on children's quality of life, physical and psychological well-being, and capacity to learn. It has also important socio-economic consequences. A better coverage is imperative itself as far as the diagnosis based on the symptoms and the allergy cutaneous tests which are easy. The options for treating allergic rhinitis in the child are not so different as those for adult. Complete avoidance of inhalant allergens is not always possible and medication are quite always possible. Intranasal corticosteroids are sometimes prescribed. In persistent disease, allergen immunotherapy may be considered according to the last OMS consensus statement. PMID- 11209471 TI - [Asthma in children]. AB - Asthma is the most common chronic condition in paediatrics. Nowadays the prevalence is of multi-factorial origin. Clinical symptoms in children are often deceptive (isolated cough, winter bronchitis, caused by effort) often to the point of delaying diagnosis. This depends on a network of clinical arguments established by indispensable complementary investigations (thoracic plate and exploration of respiratory function). Search for atopy is systematic whatever the age of the child. Therapeutic care includes educative programmes for both children and their parents. Basal treatment is necessary when the asthma is persistent. Recourse must be made to drugs of which the type and dosage vary according to the state of development. Inhaled corticosteroid is often indicated for a prolonged period. Indications for specific desensitization are now well codified. The concern cases where the allergy has a significant impact on the development of the asthma. Individualised reception plans give a better integration of asthmatic children into school. PMID- 11209472 TI - [Atopic dermatitis:epidemiologic, clinical features, the role of allergy (review)]. AB - This review includes the main epidemiological, genetic, clinical, evolutionary, and treatment elements of atopic dermatitis with a special reference to allergy and non-allergy factors that trigger pulses of atopic dermatitis. PMID- 11209473 TI - [Vaccination with allergens in children]. AB - Specific immunotherapy or allergen vaccination has been in routine use since 1911 for the treatment of respiratory allergic diseases. It is more effective in children and young adults than later in life. Its efficacy has been demonstrated in double-blind placebo controlled studies in both allergic rhinoconjunctivitis and allergic asthma. The improvement of allergenic extracts (in particular by standardization), the better understanding of the mechanisms of action of immunotherapy, the use of local administration routes and the publication of guidelines have legitimate its definite role to play in the therapeutic management of allergic respiratory diseases in childhood. PMID- 11209474 TI - Developing customer databases. AB - There is a growing consensus among pharmaceutical companies that more product and customer-specific approaches to marketing and selling a new drug can result in substantial increases in sales. Marketers and researchers taking a proactive micro-marketing approach to identifying, profiling, and communicating with target customers are likely to facilitate such approaches and outcomes. This article provides a working framework for creating customer databases that can be effectively mined to achieve a variety of such marketing and sales force objectives. PMID- 11209475 TI - The death of the four "P"s: a premature obituary. AB - To paraphrase Mark Twain the report of the demise of the four "P"s has been greatly exaggerated. While new concepts such as the four "R"s of relevance, response, relationships, and results may add value, the four "P"s remain essential. Moreover, health care marketing can benefit from the addition of a fifth "P," Prompting customers to adopt and repeat behaviors that benefit them, and a fifth "R," Reminding customers of the health and quality-of-life benefits they have gained from health care plans and providers. PMID- 11209476 TI - Factors influencing the recommendation of nursing homes. AB - This article reviews and compares the perceptions of nursing homes by residents and their proxies (family, friends, etc.) and reports that residents tended to give higher ratings to services than do their proxies. The analysis attempts to determine why residents give higher marks, which group the facility should look to for feedback, and whether the ratings will help organize the strengths and weaknesses in the facility to produce positive word of mouth within the community. PMID- 11209477 TI - Researching the market for assisted living facilities. PMID- 11209478 TI - The road to e-health: marketing implications. PMID- 11209479 TI - Marketing health care to minorities: tapping an emerging market. AB - A number of myths have prevented the development of a formal health care marketing strategy for the 100 million-plus racial and ethnic group members in the United States, despite their relatively greater need for health services. This market continues to grow in numbers, resources, and influence as the majority market level off. Marketers must look to minorities for new business, but traditional health care marketers have a long way to go before they are in a position to truly maximize this opportunity. PMID- 11209480 TI - The newborn health agenda: need for a village-level midwife. PMID- 11209481 TI - The diabetes epidemic: need for a systematic response. PMID- 11209482 TI - Type 2 diabetes in southern Kerala: variation in prevalence among geographic divisions within a region. AB - BACKGROUND: Numerous surveys carried out in India report the high prevalence of type 2 diabetes. Such studies have not included the population of Kerala. We estimated the prevalence of type 2 diabetes mellitus in Neyyattinkara taluk, Thiruvananthapuram district, Kerala state. METHODS: All panchayat wards in the taluk were grouped into urban, highland, midland or coastal, and one ward from each stratum was randomly selected for the study. All households were listed and adults, 20 years or older, screened for high (> 110 mg/dl) random blood sugar (RBS) by a glucometer test. Those with high RBS were reassessed by a fasting oral glucose tolerance test (OGTT), consisting of initial examination of venous blood for fasting plasma glucose (FPG) values, administration of 75 g of glucose dissolved in distilled water, and examination of venous blood for postprandial plasma glucose (PPPG) exactly 2 hours after the administration of glucose. Diabetes was diagnosed according to the World Health Organization criteria as either FPG > 139 mg/dl, or PPPG > 199 mg/dl, or both. Impaired glucose tolerance (IGT) was diagnosed if PPPG was 140-199 mg/dl. RESULTS: Out of 4988 eligible subjects, 3899 were available for the study, a response rate of 78.2%. Response was highest in the highland area (86.2%), and lowest in the coastal area (73.6%). The overall crude prevalence rate of type 2 diabetes was 5.9%. It was highest in the urban (12.4%), followed by midland (8.1%), highland (5.8%), and coastal (2.5%) regions. Ageing was associated with greater prevalence of type 2 diabetes in all regions and both sexes. Women showed a higher prevalence in the highland and coastal areas and men in the urban and midland areas. When compared to a population with standard age structure suggested by the World Health Organization for international comparisons, prevalence in the age group 30-64 years was found to be 16.9% in the urban, 10.1% in the midland, 6.8% in the highland and 3.6% in the coastal regions, respectively. Overall age-adjusted prevalence of type 2 diabetes in 30-64-year-olds in Neyyattinkara was 9.2% among men, 7.4% among women, and 8.2% for all persons. There was not much difference in prevalence if the American Diabetes Association criteria for diagnosis were used. The prevalence of impaired glucose tolerance was fairly low in this population. Out of 229 diabetics in the sample, 175 (76.5%) were already diagnosed and under treatment, while our survey identified 54 new diabetics (23.5%). CONCLUSION: Though prevalence of type 2 diabetes is high in this population, the detection rate is also high. However, impaired fasting glucose and impaired glucose tolerance are low. The reasons for this need to be elucidated. PMID- 11209483 TI - Influence of education and occupation on knowledge about diabetes control. AB - BACKGROUND: A global epidemic of diabetes has been predicted during the first quarter of the twenty-first century, with a substantial increase in its prevalence in India. Good management of diabetes is a necessary step towards its control and blood glucose testing forms an integral part of this. This study was undertaken to assess the importance of education and occupation in relation to knowledge about good control of diabetes. METHODS: Perception patterns regarding methods for testing blood glucose and metabolic control were assessed by the direct interview method in 793 patients with type 2 diabetes. Patients' knowledge levels were compared for different educational and occupational categories using the Normal test (z-test) and the Student's t-test. RESULTS: The difference between the mean ages of men and women diabetics was not significant (p > 0.1). It was found that 46.7% of the subjects were aware of the importance of blood glucose testing. Awareness regarding the importance of microalbuminuria, lipid profile and glycosylated haemoglobin was observed in 24.1%, 15.5% and 7.6% of patients, respectively. A positive impact of education on overall knowledge levels was observed. However, no definite relationship was found between knowledge and occupation. CONCLUSION: There was a total lack of knowledge regarding self-care of diabetes in all educational and occupational categories (including patients who were qualified doctors). This calls for an urgent need to create greater public awareness. This study may serve as a guideline for developing an educational package for different subsections of the community. PMID- 11209484 TI - Acinetobacter infection in neurosurgical intensive care patients. AB - BACKGROUND: This study was performed to analyse the incidence of Acinetobacter infections in neurosurgical patients in the postoperative period. METHODS: Two thousand three hundred and twenty postoperative cranial neurosurgical intensive care unit (ICU) patients were studied from March 1995 to August 1996; 419 patients had a variety of infections and 42 patients had multiple infections. Acinetobacter was isolated in 103 patients (24.6% of total patients infected and 4.4% of total patients analysed). Statistical analyses were performed to identify the risk factors, antibiotic sensitivity and outcome of therapy of Acinetobacter infection. RESULTS: Acinetobacter infection was not significantly related to the length of hospital stay prior to surgery but was related significantly to the length of stay in the ICU after surgery. Acinetobacter was isolated from sputum/tracheal secretions in 47/103 (45.6%), followed by cerebrospinal fluid [24/103 (23.3%)], urine [15/103 (14.56%)] and blood [15/103 (11.65%)]. Acinetobacter infection was present in 54 (3.21%) of 1680 patients who had undergone routine/elective surgery and in 49 (7.66%) of 640 patients following emergency surgery. Elective/supportive ventilation for > 5 days, external ventricular cerebrospinal fluid drainage for > 5 days, intracranial pressure monitoring and prolonged indwelling Foley's urinary catheter during the perioperative period were independent risk factors (p < 0.005). Acinetobacter isolated from sputum/tracheal secretions were mostly sensitive to amikacin, cefotaxime and ceftriaxone; while those grown from the cerebrospinal fluid were more often sensitive to ciprofloxacin, amikacin and netilmycin. Twenty-four patients succumbed to Acinetobacter infection; in 11 of these patients the organism was resistant to all antibiotics. CONCLUSION: Acinetobacter is an important nosocomial infection in neurosurgical intensive care patients. PMID- 11209485 TI - Clinical manifestations and survival pattern of Wilson's disease. AB - BACKGROUND: Wilson's disease usually presents in childhood. Early recognition and treatment is crucial to retard the progression of this disease, which can be debilitating, if not fatal. We analysed the clinical manifestations and survival pattern of patients admitted at our centre from 1993 to 1996. METHODS: Hospital records of patients were reviewed to obtain the clinical manifestations. The survival status of patients was determined by a prospective follow up. The Kaplan Meier survival curve and univariate Cox proportional hazards model were used to determine the survival pattern and risk for death in Wilson's disease. RESULTS: A total of 60 patients were studied. The median age at onset of symptoms was 12 years (range 5-52 years). The log rank test showed a significant difference in the mean (SD) survival between patients who presented with hepatic [87.36 (15.26) months] and neurological symptoms [114.33 (9.14) months]. Cox proportional hazards analysis showed a hazard ratio of 4.9 for patients with a hepatic presentation compared to those with neurological presentation. CONCLUSION: The presentation of Wilson's disease is not limited to the paediatric age group. Patients with a hepatic presentation had a five-fold higher risk of mortality when compared to those with a neurological presentation. PMID- 11209486 TI - Reactive oxygen species in health and disease. AB - With the advent of the use of oxygen as the terminal electron acceptor in aerobic respiration, came the curse in the form of reactive oxygen species (ROS). However, the evolving organism had developed elaborate defence machinery to escape from these reactive byproducts of its own metabolism, and also developed a mechanism for the utilization of these species in physiological processes to gain a survival advantage. ROS have been increasingly implicated in the ageing process and in different diseases such as cancer, Alzheimer's disease, Parkinson's disease, reperfusion injury, etc. They are also important in cellular phenomenon such as signal transduction pathways. We review the mechanisms of production of ROS in the cell, their interaction with cellular macromolecules, pathways of ROS induced cell death, the mechanisms for protection from ROS-induced damage as well as the key biological and disease processes where ROS play an important role. PMID- 11209487 TI - Further insight into the thrifty phenotype. PMID- 11209488 TI - Performing a pericardiocentesis. PMID- 11209489 TI - School drop-out: a public health approach. PMID- 11209490 TI - The pharmaceutical industry: our 'silent' partner in the practice of medicine. PMID- 11209492 TI - The knee joint replacement. PMID- 11209491 TI - Worldwide decline in birth rate--how is Africa affected? PMID- 11209493 TI - Helicobacter pylori does not cause gastric carcinoma in India. PMID- 11209494 TI - Helicobacter pylori and gastric carcinoma: evidence for the link. PMID- 11209495 TI - Some reflections on the development of psychiatry in India. PMID- 11209496 TI - Amalgam safety. PMID- 11209497 TI - Unconventional dentistry. PMID- 11209498 TI - Unconventional dentistry. PMID- 11209499 TI - The durability of intraoral devices. PMID- 11209500 TI - The need for standardization of practice among tongue piercers. PMID- 11209501 TI - Clostridium difficile colitis following antibiotic prophylaxis for dental procedures. AB - Clostridium difficile-induced diarrhea and colitis are common complications of therapeutic courses of antibiotics in the hospital setting. We report a case of Clostridium difficile colitis following antibiotic prophylaxis for endocarditis prior to dental procedures in the community setting. The infection necessitated hospital admission and a prolonged hospital stay. Dental practitioners must be aware of the significance of the disease and the risk associated with antibiotics, whether they are used for prophylaxis or treatment. PMID- 11209502 TI - Congenitally missing maxillary lateral incisors and orthodontic treatment considerations for the single-tooth implant. AB - Implant restorations have become a primary treatment option for the replacement of congenitally missing lateral incisors. The central incisor and canine often erupt in less than optimal positions adjacent to the edentulous lateral incisor space, and therefore preprosthetic orthodontic treatment is frequently required. Derotation of the central incisor and canine, space closure and correction of root proximities may be required to create appropriate space in which to place the implant and achieve an esthetic restoration. This paper discusses aspects of preprosthetic orthodontic diagnosis and treatment that need to be considered with implant restorations. PMID- 11209504 TI - Dentistry in 2020. PMID- 11209503 TI - In vitro comparison of peak polymerization temperatures of 5 provisional restoration resins. AB - BACKGROUND: The heat produced by provisional restoration materials may injure the dental pulp. This study measured and compared peak temperatures during polymerization of 5 materials used in the fabrication of provisional restorations. METHODS: The tested materials were 2 self-curing resins (Integrity and Protemp) and 3 dual-cure resins (Iso-Temp, TCB Dual Cure and Provipont DC). A mould the size of a maxillary molar tooth was fabricated to contain 0.5 cc of resin. The temperature rise of the different materials was recorded every 10 seconds over a 10-minute period. RESULTS: The rise in temperature of Integrity (peak temperature of 33.8 degrees C) and Protemp Garant (35.6 degrees C) was significantly higher than the rise in temperature of Iso-Temp (29.5 degrees C), TCB Dual Cure (28.4 degrees C) and Provipont DC (29.5 degrees C). CONCLUSION: Use of the dual-cure resins in provisional restorations may reduce the risk of pulp injury. PMID- 11209505 TI - FDI--our window on the world of oral health. PMID- 11209506 TI - [Regeneration of the immune system after bone marrow transplantation]. AB - After haematopoietic stem cell transplantation, reconstitution of bone marrow consists of two distinct phenomena, numerical recovery of bone marrow cellular elements on the one hand and functional recovery of cellular interactions on the other. Immune reactivity during the first month postgrafting is extremely low. Cytotoxic and phagocytic functions usually recover by day 100, while more specialized and cooperative functions of T and B cells remain impaired up to one year or more postgrafting. Regeneration of total CD4+ T cell number in adult (and especially in elderly) transplant recipients is severely limited and occurs largely by peripheral expansion of mature CD4+ T cells. While restoration of total CD8+ T cell number is commonly seen in adults, potentially important alterations in the subset composition of CD8+ populations remain. Contracted T cell repertoires for CD4+ and CD8+ T cells are consistently found in adults after T cell regeneration. This suggests that thymic function is frequently limiting in adults and that thymic-independent pathways are insufficient for restoring host immunocompetence. Although there are similarities in immune reconstitution after alllo- and autologous haematopoietic stem cell transplantations, allogeneic transplantation involves graft versus host disease and the use of immunosuppressive therapy to control it, both of which further interfere in the early developmental stages of immune reconstitution. PMID- 11209507 TI - [Experiences with determination of cardiac Troponin-I and CK-MB serum levels in acute coronary syndrome]. AB - The consideration of the correct diagnosis and prognosis in acute coronary syndrome seems to be a great challenge for cardiologists. Measuring of the serum cardiac Troponin (cTI) level may help solution of this problem. According to the authors the myocardial infarction has been revealed with a great sensitivity and specificity by the cTI level (100%). Authors found a higher level of cTI even after 72 hours of the onset of symptoms of myocardial infarction. After thrombolysis the wash out phenomen was more expressive compared with the values of CK-MB enzymes. A moderate but significant increase was observed of the cTI level in unstable angina. The measuring of cTI in acute coronary syndrome gives an important information to the correct diagnosis. The prognostic considerations of cTI level in unstable angina are interpreted by authors according to relevant data of literature. PMID- 11209508 TI - [Normal percentiles of kidney size in children as measured by ultrasonography]. AB - The most anomaly of kidney development and urinary tract diseases have an effect on the size of the kidneys. Kidney size (renal length and parenchymal thickness) is readily measurable by ultrasonography, but the evaluation remains subjective without the use of appropriate standards. The aim of authors was, to produce a centile chart for normal kidney size based on US measurement in healthy Hungarian children. Renal length and renal parenchymal thickness (upper pole, middle part and lower pole) as well body weight and height were measured in 330 children. Normograms (centile charts) with 10th, 50th and 90th centiles were produced for body weight/height and renal length/parenchymal thickness. Renal length correlated strongly with both body weight (r = 0.93, p < 0.001) and height (r = 0.93, p < 0.001). The centile chart for renal size enables the objective evaluation of abnormal kidney size; it can help in the early recognition and follow up of urinary diseases. PMID- 11209509 TI - [Dr. Imre Fauszt (1908-1981)]. PMID- 11209510 TI - [Medicine in ancient Mezopotamia]. PMID- 11209511 TI - Anterior and posterior nasal fontanelles. PMID- 11209512 TI - Managing glottal incompetence following Teflon injection. PMID- 11209513 TI - Deep facial infection of odontogenic origin. PMID- 11209514 TI - Electronystagmography: nausea on extension of the neck. PMID- 11209515 TI - Recurrent laryngeal nerve paralysis: current concepts and treatment: Part III- Surgical options. PMID- 11209516 TI - Hydroxyapatite cranioplasty in fibrous dysplasia of the skull. AB - We describe the case of a woman who had complained of worsening headache during the previous year. Analysis of computed tomography imaging and biopsy led to a diagnosis of fibrous dysplasia of the skull. A symptomatic frontal bone lesion was removed, and the resulting defect was repaired with hydroxyapatite cement. Hydroxyapatite cement has several advantages over hydroxyapatite ceramic blocks and granules, and it is particularly well suited for calvarial reconstruction. PMID- 11209517 TI - The effect of recreational gunfire noise on hearing in workers exposed to occupational noise. AB - Hearing sensitivity for an experimental group of 278 industrial workers who engaged in recreational shooting was compared with that of an age-matched control group of 278 nonshooting industrial workers to examine the effect of gunfire exposure on auditory thresholds. The influence of age and the number of unprotected gunshot exposures per year also was examined. The subjects in the experimental group completed a questionnaire to define the types of firearms used, the number of years shooting, and the number of protected and unprotected gunshot exposures per year. Results revealed that hearing sensitivity for frequencies 3.0, 4.0, and 6.0 kHz for both ears in the experimental group was an average of approximately 5 to 10 dB poorer than that of the control subjects. Although both subject groups demonstrated poorer 3.0-to-6.0-kHz hearing sensitivity for left-ear compared with right-ear listening, the degree of asymmetry between ears was greater for the experimental subjects. Older shooters had more hearing loss and greater threshold asymmetry than younger shooters, but there was no significant relationship between hearing sensitivity and the number of unprotected exposures per year. This latter finding was attributed to a fourfold increase in the number of unprotected annual exposures that were reported by younger shooters, who had inherently better hearing than did the older shooters. PMID- 11209518 TI - MRI video diagnosis and surgical therapy of soft tissue trauma to the craniocervical junction. AB - We evaluated objective diagnostic methods for patients with possible upper cervical spine instability caused by trauma and correlated them with subsequent neurosurgical findings and outcomes. Between November 1995 and May 1998, we investigated 420 patients with functional magnetic resonance imaging (MRI) of the craniocervical junction. We evaluated the extracranial vertebral circulation by MRI angiography, with focus on the position of the dens and on the subarachnoid space during entire rotational maneuvers. We documented 72 cases (17.1%) of injuries to the alar ligaments that were accompanied by signs of instability. Twenty patients (4.8%) had a complete alar ligament rupture, and 52 (12.4%) had an incomplete rupture with coexisting instability. We referred these patients to a neurosurgeon. Surgery was eventually chosen for 42 patients (10.0%) with the intention of obtaining dorsal occipitocervical stabilization. The duration of time between the MRI evaluation and surgery ranged from 1 week to 1.5 years (mean: 3.5 mo). After the fifth postoperative day, almost all symptoms had disappeared. One year following surgery, 34 of the 42 patients (80.9%) still demonstrated successful fusion and an alleviation of their sensation of instability. Twenty-five of these patients (59.5%)--all of whom were unemployed before surgery--were able to resume a professional activity. In the eight patients (19.0%) who still had a loss of stability during the second and 14th weeks, we noticed that there were some negative effects of rehabilitation. Six of these patients developed pseudarthrosis or osteolysis of their bone grafts during the first 3 months after fusion, and three required a repeat operation. We conclude that functional MRI with lateral tilting and rotatory evaluation is a useful tool for investigating craniocervical instability. For patients who are recalcitrant to following a program of conservative therapy, surgical stabilization of the craniocervical junction appears to be justified. PMID- 11209520 TI - Large osteoma of the external auditory canal. PMID- 11209519 TI - Flexible esophagoscopy as part of routine panendoscopy in ENT resident and fellowship training. AB - We conducted a retrospective study to evaluate the use of flexible esophagoscopy as part of routine panendoscopy in an academic setting. We reviewed the results of 378 procedures that were performed over a 4-year period in an academic otolaryngology--head and neck surgery program for residents and fellows. Medical records were reviewed for early and late complications as well as for adequacy of the examination. We found no immediate or long-term complications associated with flexible esophagoscopy. Adequate examination was achieved in all but two cases (99%), both of which involved patients who had significant strictures related to radiation therapy and who were not able to be evaluated by rigid esophagoscopy. We conclude that flexible esophagoscopy is a safe and accurate means of evaluating the esophagus during a panendoscopic evaluation of the upper aerodigestive tract, and that it should be included in the diagnostic armamentarium of every otolaryngology--head and neck surgery resident and fellow. PMID- 11209521 TI - [Diagnostic criteria of atypical benign partial epilepsy syndrome in childhood]. AB - The paper presents an analysis of clinical-neuropsychological peculiarities of the syndrome of atypical benign partial childhood epilepsy (pseudolennox syndrome) of 6 patients (3 boys, 3 girls). An age of the onset of the disease was between 1.5-4 years. There was polymorphism of paroxysms, their high frequency with an obligate presence of hemifacial fits and atypical absences. Night generalized tonic-clonic attacks and the falling attacks were found in 67% of the patients. Spectrum of the neurological disorders included disorders of speech and a slight cerebella symptomatology. Regional "rolandic" activity and diffuse epileptiformed disorders, increasing into a phase of a slow sleep, were registered by EEG. Resistance to anticonvulsive therapy was revealed. The authors had demonstrated a nosologic independence of pseudolennox syndrome and had considered worth while to pick it out in a group of cryptogenic partial forms of epilepsy together with the epileptic aphasia of Landu-Kleffner and an epilepsy with the continuous peak-waves during the slow sleep. PMID- 11209522 TI - [Rett's syndrome: diagnostic issues]. AB - Rett's syndrome (RS) is a severe disease of an early childhood, affecting girls mainly and manifesting in autistic symptoms, severe mental regression and motor dysfunction. The aim of the study was to analyze both early stages of clinical symptomatology and EEG correlates of RS. 65 patients aged 2.5-13 years with classic RS were examined. It was found that affective and autistic manifestations were the main symptoms during the 1-st stage of RS in approximately 50% of the cases. Two variants of classic RS were described according to the degree of motor dysfunction and behavioral disturbances: RS with motor disorders; RS with schizophrenoform disorders. Analysis of 145 EEG of 62 patients with the III-d PS stage revealed a presence of some correlations between location of the focus of the rhythmic theta-activity and clinical manifestations as well as their prognostic value. Thus, the decrease of the index of the rhythmic theta-activity in the patients on the III-d stage of RS correlated significantly with the improvement of the attention, behavioral and social activity, while its increase correlated with both the change for the worse of the higher cortex functions and advance of the motor disorders. PMID- 11209523 TI - [Neuroimaging diagnosis and aspects of therapy of hemorrhagic stroke]. AB - The peculiarities of the clinical manifestations of the hemorrhages into the brain were analyzed in 215 patients regarding both the degree of the blood break into the ventricular system and the size of the perifocal edema. It is demonstrated that the clinical picture, course and prognosis of the disease depend on the volume of the hemorrhage, the degree of the ventricular tamponage, presence of both acute occlusive hydrocephalus and secondary truncal syndrome. The presence of the blood in the ventricular system was not fatal, but, in some cases, led to the improvement of the patients' state because of the decrease of the voluminal influence of the hematoma. Therapy of patients with hemorrhagic strokes must be differential and be determined by the size of the perifocal edema in the ischemic tissue, the state of the system of the hemostasis as well as the presence of angiospasm of intracerebral vessels. Combined administration of calcium antagonists, antioxidants, antiedemic and antiprostaglandin preparations was grounded. PMID- 11209525 TI - [Psychometrics is not only for experiments]. PMID- 11209524 TI - [Aspects of psychotherapy in diabetes mellitus with accompanying alcoholic intoxication]. AB - 120 patients with different types of diabetes mellitus were divided into groups by the presence and intensity of accompanying alcoholic intoxication: group 1--no alcohol intake; group 2--rare alcohol intake; group 3--moderate alcohol intake; group 4--alcoholic abuse. Experimental psychological methods were used together with psychotherapeutic approaches: Wiesbaden's questionnaire (WIPPF), Lusher's and MMPI tests. For each group of the patients some recommendations are given for application of the above techniques. Thus in patients from the 1-3 groups it is worthwhile to perform a positive psychotherapy directed to the development of the body/sensation sphere (according to WIPPF), that is a care about physical and mental state (including autotraining and training of communication). In the alcohol abusing patients the main point should be fantasy/future sphere (according to WIPPF) in the ranges of the same positive psychotherapy directed to forming positive world view and correction of the interpersonal relations. PMID- 11209526 TI - [The 100th anniversary of the Korsakov Neurology and Psychiatry Journal]. PMID- 11209527 TI - [Diagnostic and prognostic significance of the antibodies to the myelin basic protein in acute neuroinfections in children]. AB - The development of severe CNS damages including encephalitis is highly probable in some respiratory and exanthemata viral infections (measles, rubella, parotitis). A high level of IgG antibodies to the myelin basic protein was found in patients with parotitis meningitis and rubella encephalitis but it was not high in 80% of patients with encephalitis of the unclear etiology and in 25% of cases with rubella encephalitis. More accurate analysis of clinical, neurovisual and immunologic data revealed a link of appearance of such complications with both the presence of more pronounced demyelinization and prolongation of the disease. PMID- 11209528 TI - [Autoantibodies to nerve growth factor and astroglial protein S-100 in Rett's syndrome]. AB - The levels of autoantibodies (AAB) to nerve growth factor (NGF) and to S-100 protein were examined in blood of both mentally normal girls and girls with Rett's syndrome (RS). The elevated titer of anti-NGF AAB, but not of anti-S-100 AAB was determined in the blood of patients with RS. There was relative individual stability of anti-NGF AAB level which didn't depend on the stage of the disease. At the same time, a reverse correlation was found between the level of these antibodies and severity of the disease: the mild form of the disease (with relative preservation of the speech elements and locomotor functions as well as with the later age of the onset of the disease and the later development of the regressive symptoms) is characterized by the higher AAB level. Autoimmune processes role (anti-NGF AAB) in formation of RS clinical features is discussed. PMID- 11209529 TI - [World Health Organization in the beginning of the XXI century]. PMID- 11209531 TI - [Laboratory methods in epilepsy and disorders of cerebral circulation]. PMID- 11209530 TI - [Epidemiology of stroke in Siberia]. AB - Based on WHO MONICA methods and diagnostic criteria, it is shown that first-ever stroke incidence and mortality in Siberia (a total number of residents included in the analysis varied from 450,000 to about 800,000) that are among the highest in the world. In Novosibirsk, for the period from 1982 through 1991 there was a trend towards decreasing stroke incidence and mortality rates, but for the period from 1992 through 1997 there was a trend towards increasing there rates in both men and women. Age-standardized (US white population was used as a standard) stroke incidence rates increased from west to east and from south to north across Siberia, with a corresponding increase in the proportion of hemorrhagic strokes. In 1987-1988, age-adjusted stroke incidence rate in Novosibirsk was 212 per 100,000 residents per year, in Krasnoyarsk--325, in Tynda--329, in Anadyr--348. Stroke-case fatality rates ranged from 28% in Tynda to 41% in Anadyr. A multivariate regression analysis revealed that hypertension, left ventricular hypertrophy, ischemic heart disease. mitral valve disease, current cigarette smoking, excessing body mass index, winter season, and low ambient temperature are all significant and independent risk factors for the occurrence of ischemic stroke in Novosibirsk. A significant association between stroke occurrence and air pressure/geomagnetic activity change was found. Possible reasons for such unfavorable trends in stroke incidence in Siberia are discussed, and an optimal approach for improving organization of cerebrovascular disease care is suggested. PMID- 11209532 TI - [Molecular genetic risk factors of Alzheimer's disease]. PMID- 11209533 TI - [Is a clinical nosologic direction in the Russian psychiatry completely exhausted itself?]. PMID- 11209534 TI - Does body mass index of infertile women have an impact on IVF procedure and outcome? AB - PURPOSE: The objective was to explore whether body mass index (BMI) of women related to the different parameters of the in vitro fertilization (IVF) procedure and outcome. METHODS: This retrospective study on 398 couples analyzed epidemiological features, characteristics of ovarian stimulation, number and quality of retrieved oocytes, as well as pregnancy outcome according to three groups of BMI values: BMI < 20, 20 < or = BMI < 25 and BMI > or = 25 kg/m2. RESULTS: The prevalence of underweight and overweight women was 21.8% and 22.3%, respectively. The mean ratio follicle-stimulating hormone-luteinizing hormone increased significantly according to BMI. An increase in the mean number of consummated gonadotropin ampoules together with a decrease in the number of collected oocytes was observed in long stimulating protocol cycles when BMI > or = 25 kg/m2. The same observations were made in short stimulation protocol cycles of BMI < 20 and > or = 25 kg/m2. No significant difference could be found in clinical pregnancy and miscarriage rates between underweight, normal weight, and overweight patients. CONCLUSIONS: Both underweight and overweight have negative effects on IVF parameters and outcome leading to decreased chances of pregnancy. PMID- 11209535 TI - A comparison of psychological functioning in women at different stages of in vitro fertilization treatment using the mean affect adjective check list. AB - PURPOSE: The objectives were to identify the stage/s of IVF treatment where a woman is most vulnerable to psychological stress, and to assess the Mean Affect Adjective Check List (MAACL) as a measure of psychological functioning during IVF treatment, which has hitherto not been reported. METHODS: Thirty-seven women undergoing IVF treatment according to the long protocol of controlled ovarian stimulation completed the MAACL questionnaire at the following stages: (a) before treatment (visit 1), (b) before embryo transfer (visit 2), and (c) before pregnancy test (visit 3). RESULTS: Apart from anxiety scores for visit 2, the hostility, depression, and state anxiety scores for visit 3 were higher than the corresponding scores for visits 1 and 2 (P < 0.001). Anxiety scores for visits 2 and 3 were similar. CONCLUSIONS: Psychological counseling should be targeted at women after embryo transfer and leading up to the pregnancy test. The MAACL is a useful method for measuring psychological stress in women during IVF treatment. PMID- 11209536 TI - Recombinant human follicle-stimulating hormone for ovulation induction in polycystic ovary syndrome: a prospective, randomized trial of two starting doses in a chronic low-dose step-up protocol. AB - PURPOSE: The aim was to compare the follicular response to 37.5 and 50 IU of recombinant follicle-stimulating hormone (FSH) as starting doses for ovulation induction in patients with polycystic ovary syndrome (PCOS). METHODS: Prospective, randomized, crossover study including 15 women with clomiphene citrate-resistant chronic anovulatory infertility. Patients were treated with subcutaneous recombinant FSH at starting doses of 37.5 IU and 50 IU, respectively, according to a low-dose step-up protocol. Each woman received both treatments, in a randomized order, with an interval of > or = 1 month between treatments. RESULTS: All treatment cycles were ovulatory after an appropriate follicular response and hormone levels were similar with both treatments, although the total quantity of FSH required and the mean daily dose required to induce identical follicular development were significantly lower with a starting dose of 37.5 IU FSH. The mean duration of treatment to achieve ovulation was approximately 13 days with both treatments but treatment periods > or = 20 days were required in some patients. CONCLUSIONS: In women with PCOS, a starting dose of 37.5 IU recombinant FSH may be adequate to induce follicular growth. However, the use of low starting doses may result in some cases in increased treatment periods and need for monitoring. PMID- 11209537 TI - IVF performance of women who have fluctuating early follicular FSH levels. AB - OBJECTIVES: The aim was to evaluate whether women who have early follicular follicle-stimulating hormone (FSH) levels > 12 mIU/ml have reduced response to follicular stimulation for in vitro fertilization (IVF) in a following month, in spite of normal FSH levels. MATERIAL AND METHODS: In a 3-year period from January 1996 to December 1998, 303 women aged 38 years and above and/or who had previously responded poorly to superovulation for IVF gave blood samples for FSH, luteinizing hormone (LH), and estradiol (E2) on day 2 of menstruation before commencing treatment. RESULTS: In 117 (38.6%) of these women, FSH levels were > 12 mIU/ml (range 12-114 mIU/ml). Sixty-six of these women gave a further 130 blood samples for FSH measurement in the following months. Seventy-eight (60.0%) of the tests showed raised FSH value > 12 mIU/ml. Thirty women whose repeat FSH levels were < 12 mIU/ml underwent 41 IVF cycles (group 1). Sixty-three other women, older than 38 and/or who had a poor response to superovulation previously and whose FSH levels were < 12 mIU/ml, served as the control group (group II). There were no differences in the responses to superovulation and delivery rates between the two groups (14.6% vs. 12.7%). CONCLUSIONS: Women whose early follicular phase FSH levels were raised > 12 mIU/ml had an increased risk (> 50%) that in subsequent cycles levels would remain raised, and it was not possible to predict which individuals would have favorable FSH levels. If the cycle day 2 FSH level returns to a "normal" level of < 12 mIU/ml, women aged 40 and above had substantial cycle cancellation rates (43%), but patients who achieved the stage of embryo transfer had a good chance of conceiving, regardless of their age. PMID- 11209538 TI - Clinical correlation of cyclin D2 mRNA expression in human luteinized granulosa cells. AB - PURPOSE: The aim was to evaluate whether the expression of cyclin D2 mRNA in human luteinized granulosa cells correlates with the clinical parameters of women undergoing in vitro fertilization-embryo transfer (IVF-ET) programs. METHODS: Using reverse transcriptase-polymerase chain reaction (RT-PCR) techniques, the cyclin D2 mRNA in human luteinized granulosa cells of large follicles was measured. Correlation analysis between cyclin D2 mRNA expression and clinical parameters [age; day 3 follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2); E2 and P4 at the day of human chorionic gonadotropin (hCG); total amount of gonadotropin and the number of days of gonadotropin administration; pregnancy outcome] were performed. RESULT(S): Cyclin D2 mRNA expression showed negative correlation with patient's age (R = -0.60, P < 0.005) and total amount of gonadotropins (R = -0.45, P < 0.03), and also showed positive correlation with serum E2 levels at the day of hCG administration (R = 0.55, P < 0.02). Other clinical parameters showed no statistical significance. Cyclin D2 mRNA expression of pregnant group was higher than that of nonpregnant group (P < 0.03). CONCLUSIONS: Cyclin D2 mRNA expression in human luteinized granulosa cells positively correlates with clinical parameters of ovarian function and may be a novel marker for the health of human ovarian follicle. PMID- 11209539 TI - Effects of controlled ovarian hyperstimulation on oocyte quality in terms of the incidence of apoptotic granulosa cells. AB - PURPOSE: The aim was to investigate which ovarian hyperstimulation protocol performed in the same patients causes development of oocytes of good quality. METHODS: Twenty normo-ovulatory women underwent three different controlled ovarian hyperstimulation protocols for in vitro fertilization-embryo transfer. Patients underwent follicle aspiration after administration of human chorionic gonadotropin (hCG). The total number of retrieved oocytes, the number of mature oocytes, and the rate of mature oocytes were examined. Recovered granulosa cells were stained with Hoechst 33258 and examined by fluorescence microscopy to estimate the incidence of apoptotic cells. RESULTS: The total number of oocytes and the number of mature oocytes in gonadotropin-releasing hormone agonist (GnRHa) + human menopausal gonadotropin (hMG) + hCG and hMG + hCG cycles were higher than those in the natural cycle (P < 0.0001). The rate of mature oocytes in hMG + hCG cycle was the highest among the three protocols (P < 0.04). In the mural granulosa cells, the incidence of apoptotic cells in the GnRHa + hMG + hCG cycle was significantly higher than those of the natural (P < 0.002) and hMG + hCG cycles (P = 0.0002). The incidence of apoptotic cumulus granulosa cells in the GnRHa + hMG + hCG cycle was significantly higher than those of natural and hMG + hCG cycles (P < 0.002). Moreover, the incidence of apoptotic cumulus granulosa cells in the hMG + hCG cycle was significantly lower than that in the natural cycle (P < 0.01). CONCLUSIONS: These results indicated that hMG + hCG is the most appropriate controlled ovarian hyperstimulation protocol among the three examined with regard to oocyte quality. PMID- 11209540 TI - Low-dose aspirin does not increase implantation rates in patients undergoing intracytoplasmic sperm injection: a prospective randomized study. AB - PURPOSE: The aim was to evaluate the effect of aspirin on pregnancy and implantation rates in an unselected group of patients undergoing intracytoplasmic sperm injection (ICSI). METHODS: Two hundred and seventy-nine patients were randomized to receive 80 mg of aspirin (n = 139) or no treatment (r = 136) starting from the first day of controlled ovarian hyperstimulation. RESULTS: Duration of stimulation, gonadotropin consumption, peak estradiol, number of oocytes retrieved, fertilization rate, cleavage rate, and number of embryos transferred were similar in the two groups. Implantation and clinical pregnancy rates were 15.6% and 39.6% versus 15.1% and 43.4% in aspirin treated and untreated groups, respectively (P > 0.05). CONCLUSIONS: Low-dose aspirin administration does not improve implantation and pregnancy rates in an unselected group of patients undergoing ICSI. PMID- 11209541 TI - Characteristics of cryopreserved semen from men with lymphoma. AB - PURPOSE: This study compared the pretreatment semen quality in patients with Hodgkin's disease and non-Hodgkin's lymphoma with a group of healthy donors. We also examined the differences in prefreeze and postthaw semen quality among the different stages of Hodgkin's disease. METHODS: The study included 89 patients with Hodgkin's disease, 18 with non-Hodgkin's lymphoma, and 50 healthy sperm donors. RESULTS: In patients with Hodgkin's disease, the prefreeze and postthaw semen characteristics were significantly lower than those of the healthy donors. Similar results also were seen in patients with non-Hodgkin's lymphoma. No significant differences in the prefreeze semen quality were seen in patients with different stages of cancer. CONCLUSION: Patients with Hodgkin's disease and non Hodgkin's lymphoma in our study had poor semen quality when compared with healthy donors both before and after cryopreservation. As cancer therapy significantly impairs reproductive potential, sperm banking should be offered to these men before the start of their therapy. PMID- 11209543 TI - [Cutaneous tuberculosis yesterday and today]. AB - Cutaneous tuberculosis were very frequent in Europe until the middle of the 20th. Century in which their incidence decreased drastically as a consequence of the specific treatments. On the other hand, the M. bovis caused infections which were previously very common have also been disappearing due to control of milk and the livestock produced for eating purposes. Cutaneous tuberculosis have classically been divided into two groups: typical tuberculosis, with follicular structure and demonstrated bacillus by culture or inoculation and atypical tuberculosis (tuberculids), in which there are no follicular structure and the bacillus is not isolated. Its relationship with tuberculosis is principally based on the personal and/or familial background and on the strong positivity of the Mantoux reaction. The concept of tuberculide has always been under debate. Above all in the second half of the 20th. Century, most of the authors were skeptical in regards to its tuberculous etiology. However, since the 1990's, determinations of bacillary DNA in the lesions by the PCR technique has made it possible to demonstrate the M. tuberculosis in them. At present, due to the probably re-emergence of tuberculosis in general as consequence of the immunodeficiency (AIDS), of the M. tuberculosis strains resistant to treatment, and of the cases imported by immigration, some increase in the incidence of cutaneous tuberculosis can be predicted in the future, although it need be feared that this will reach the amounts of other periods. On the other hand, immunodeficiences have made the anergic forms, such as tuberculosis cutis miliaris diseminata or tuberculous gumma, which were previously rare, less rare al present. PMID- 11209544 TI - [Palliative medicine in oncology]. AB - The aim of Palliative Medicine is the study of the illness person and the preservation and defence of his dignity. It is not only not opposite to Curative Medicine but also complementary. It includes physical, psychological, social and spiritual factors. Palliative Medicine must be present from the diagnosis through the different evolutive stages of our patients. It is not only the care programs for terminally cancer patients. Surgery, radiotherapy and chemotherapy are used as specific palliation in some situations in order to improve quality of life, survival time or symptomatic control. Human dignity is based on the fact of being, apart from its circumstances or its abilities. When a patient tells us:- Doctor, I don't want to live. We should translate:--Doctor, I don't want to live ... this way. Then, we should wonder how are we taking care of this person. Good caring begins in a good information along the whole process. I summarize it, as progressive and bearable truth. The key to get an appropriate treatment of our patients is to combine the pharmacological, dietetic an physical treatment with a deep understanding of the human being that should inform the whole medical practise. PMID- 11209542 TI - Assessing the chromosome copy number in metaphase II oocytes by sequential fluorescence in situ hybridization. AB - PURPOSE: Aneuploidy in oocytes is the main cause of failed embryo implantation and of miscarriage. At present, only limited data on the prevalence of aneuploidy in freshly collected human oocytes are available and all studies have been performed with conventional methods for karyotyping. In this feasibility study, multiple-hybridization fluorescence in situ hybridization (FISH) was evaluated as an alternative method to determine the number of chromosomes in oocytes. METHODS: Fifty-two spare oocytes were collected from 23 patients treated with gonadotropins for intrauterine insemination or intracytoplasmic sperm injection. A conventional dual color FISH approach using mixtures of chromosome-specific standard alpha-satellite probes was applied consecutively to the chromosomes of the same metaphase II oocyte. Mixtures of three to six probes were designed in order to allow chromosome identification based on signal color and centromeric index. RESULTS: One hybridization cycle was possible in 52 uninseminated metaphase II oocytes, two hybridizations in 43 oocytes (82.7%), three hybridizations in 30 oocytes (57.6%), four hybridizations in 27 oocytes (51.9%), and five hybridizations in 15 oocytes (28.8%). Altogether, 591 chromosomes could be marked (47.4% of the entire chromosome complement, 11.4 chromosomes per oocyte). The most important single factor contributing to technical failure was loss of the oocyte from the slide. CONCLUSION: This feasibility study demonstrates that multiple-hybridization FISH can be used for the assessment of a larger proportion of the chromosome complement in oocyte as compared to previous studies based on FISH. PMID- 11209545 TI - [Physical pain and suffering in the child]. AB - Since about ten years ago there has been a great interest in the treatment of pediatric pain, previously neglected in medical practice. A review of procedures of pain assessment is made: self-assessment, behavioural analysis and biological measurements. The main therapeutic procedures are also reviewed (drugs, physical agents and psychological treatment), emphasizing the interest of prophylaxis and parental participation in children's pain treatment. PMID- 11209546 TI - [Balneotherapy, health care and public health]. AB - The actual interest of Spa-therapy in public health is considered as a way of improving health, well-being state or as prevention or treatment of different diseases. The various definitions of health are exposed and its possible influence in human beings, and in particular the complexity of the Spa-therapy. The possible positive effects of the Spa-therapy have been tested in the official Centers of several countries and have been considered of great value in Health Education its signification as a primary, secondary and tertiary health agent. PMID- 11209547 TI - [Serotonergic innervation of the auditory receptor]. AB - The serotonergic inervation of the auditory receptor is composed by nerve fibres of multipolar neurons located on the superior lateral oliva. These neurons could correspond to outer elements of the nucleus reticularis caudalis. The peripheral projection on the auditory receptor is composed of varicose fibres distributed within the inner spiral bundle connecting on inner hair cells. Other fibres, after a spiral pathway within the Corti's tunnel, reach the outer hair cells. This new fascicle, with a particular origin and peripheral distribution, characterized as serotonergic and of unknown function, could be considered as a previously undescribed projection of the reticular formation on the auditory receptor. PMID- 11209548 TI - [Metabolic syndrome X in women]. AB - The author exposes the present concept of metabolic syndrome X, which is a complex of Type II diabetes, obesity, hypertension and vascular problems. This syndrome has been known for many years, but it has been individualized as such only recently. This is due to the huge importance that obesity is reaching in developed countries, especially in the U.S.A. Today this is a very important health problem. In this work, in addition to the description of the syndrome, which is purely an internal medicine issue, its relation to some women-specific problems is also explained, especially to the so-called polycystic ovary. PMID- 11209549 TI - [Emerging mycoses]. AB - The incidence of new pathogenic agents in the fungi group has been on the rise over the past few years. This can be explained by the similar increase in elderly patients, precarious situations or immunodeficient states, together with the high degree of instrumentation in hospitals and the indiscriminate use of antibiotics and antimycotics both to cure and prevent. This study includes emerging fungi, isolated in the aforementioned individuals, which belong to the filamentous and dimorphic fungi groups, and yeasts. In view of their number, only the main ones are mentioned, together with the clinical manifestations they produce and the grounds for their diagnosis and treatment. PMID- 11209550 TI - [Chlamydia pneumoniae and vascular pathology]. AB - An updating of the microbiological and diagnostic characteristics of Chlamydia pneumoniae is carried out, and a hypothesis formulated for its probable role in the production of the atheromatous plaque. Furthermore, the immunological results obtained from patients with peripheral vascular pathology, pneumonia from C. pneumoniae, or other genital processes from C. trachomatis, and a healthy control group are included. The presence of C. pneumoniae was revealed by PCR techniques in biopsies from patients with vascular pathology in a high percentage, particularly in samples from the carotid artery (74%) or the aortic wall (83%). The true pathogenic power of Chlamydia in vascular processes in questioned. PMID- 11209551 TI - [Comparative study of iodine and thyroid gland in biological processes: development and reproduction]. AB - Iodine is an scarce metalloid, essential for life, more abundant in the aquatic ecosystem than in land. Marine species do not need to store and transform the inorganic iodine into organic iodine through the thyroid gland. Adaptation to terrestrial ecosystem has required phylogenetic processes, and animal species have used different strategies to solve the iodine captation problem according to their needs. Jellyfish lack of thyroid gland while lampery developed the thyroid gland during evolution in order to adapt to the terrestrial ecosystem. This review is a comparative phylogenetic study of thyroid gland development and iodine physiology, includes functional disorders, as well as iodine captation ability and requirements during growth and reproduction in different species. PMID- 11209552 TI - [Physiopathologic implications of telomerase]. AB - Telomerase is a specialized RNA-directed DNA polymerase that extends telomeres of eukaryotic chromosomes. Telomerase gene expression is active in germinal, stem and tumoral cells and repressed in normal human somatic cells. Activation of telomerase involves immortalization, while repression of this enzyme involves the shortening of telomeres in each round of chromosomal replication. Telomere shortening constitutes a mechanism for cells to control cell division and the entrance in the replicative senescence state. If the expression of this enzyme is forced, senescent human cells will extend their life span reaching the immortalization and malignization of the cells. Activation or depression of telomerase activity has important implications in aging and cancer therapy. Telomerase regulation is a multifactorial process in which telomerase expression, post-translational protein-protein interactions and protein phosphorylation are involved. PMID- 11209553 TI - [The health of the members of the Academy]. AB - The present paper, analyses the health of the numerary members of the Academy since 1791 until 1998 as evaluated through mortality and supervivence registers from birth or until their entrance as members. A positive trend of 3.67 years in life expectancy appears as compared to male spaniards of their time. Finally, biasses of this work are discussed as well as possible factors that could have played a role in this life expectancy mirease. PMID- 11209554 TI - [Does internal medicine still survive?]. AB - The author suggest in his lecture in the present of the well versed Royal Academy National of Medicine, the concept, current situation and future of Internal Medicine. After a brief explanation of its creation and development, in several european and north american medical schools, he analyzes the present situation of Internal Medicine coming to the conclusion that, as a result of the fragmentation of medicine into countless sub-specialties, its survival is even being questioned as a medical specialty itself. PMID- 11209555 TI - [Current interest of antipneumococcal vaccination]. AB - Pneumonia acquired in Community (CAP) may be a primary disease occurring in healthy individuals or secondary to predisposing factors or comorbidity. Prevalence of CAP is 2.6 to 5% for all ages, in USA 12%, for over 65 years 30%. Streptococcus pneumoniae is the commonest pathogen 30-50%, H. influenzae in COPD, the atypical pneumonia Mycoplasma pn., M. catharralis, Legionella pn., Enterobacteria, anaerobics often in hospital survey. In children is different RSV, Parainfluenzae type 3, Rhinovirus in the first 2 years old. Others are S. pneumoniae, H. influenzae, Chlamydia sp., etc. Appropriate empiric antibiotic therapy choices are based in guidelines. The most common pathogen is S. pneumoniae, isolates raised resistance rates to Penicillin to 20-50%, 40% in our country and also to Macrolides, with potential clinical failure (21-40%). Specially in elderly people and with the comorbidity are recommended the 23 valent polysaccharide vaccine, effective in bacteremic pneumonia 70-80%. Is not effective in children under 2 years, for that is important conjugated vaccine Hib (toxoids T, D, CRM197, OMP Nm) to prevent carriers, otitis media and reduce exacerbation of these respiratory infections. PMID- 11209556 TI - [Present and future of infectious epidemiology]. AB - A revision is made on the important biological phenomenon of microbial emergency, based on model infection diseases in which the author can give the own experimental results and experience. The concept of microbial emergency has shocked the traditional infectious epidemiology since 1983 when the HIV virus was discovered and the informatic network reached an optimum efficiency. In despite of the global risk of contagion it is necessary to consider the proximity effect in a space-time model as the main cause of infectious diseases diffusion. PMID- 11209557 TI - [Current considerations around the search for extraterrestrial life]. AB - In this paper, the current cosmological topics are considered: a) The fourth centenary celebration of Giordano Bruno's death at the Roman's inquisition stake. This eminent philosopher, based on the Coppernican Revolution, concibed the Cosmos as a infinite universe with innumerable inhabited worlds. He acted on reason to believe not only in extraterrestrial life but in extraterrestrial intelligent life. Here we write a few words in his memory and honour. b) The active project SETI@home in the framework of today's classic program "Search for Extra-Terrestrial Intelligence", by means of the reception of radioelectrical signals. c) Search for extrasolar planets. PMID- 11209558 TI - [A century of evolution, and revolution, in research and development of drugs]. PMID- 11209559 TI - Laboratory demonstration of vascular smooth muscle function using rat aortic ring segments. AB - This laboratory exercise uses a simple preparation and a straightforward protocol to illustrate many of the basic principles of vascular biology covered in an introductory physiology course. The design of this laboratory allows students to actively participate in an exercise demonstrating the regulation of arterial tone by endothelial and extrinsic factors. In addition, this hands-on laboratory allows students to gather data using well-known basic biomedical research techniques. Specifically, students are introduced to an isolated organ-chamber technique that is widely used to study cellular mechanisms of many tissues including vascular smooth muscle contraction and dilation. On the basis of student evaluations, participation in the experiments and interpreting data reinforce lecture materials on smooth muscle and endothelial cell function and illustrate mechanisms regulating vascular tone. Students come away with a greater understanding of vascular biology, a deeper appreciation of integrative physiology, and an understanding of the process of conducting tissue-chamber experiments. PMID- 11209560 TI - The Claude Bernard Distinguished Lecture. Teaching in the year 2061. PMID- 11209561 TI - Please pass the cauliflower: a recipe for introducing undergraduate students to brain structure and function. AB - Neurophysiology/pathophysiology content is a frequent source of anxiety for undergraduate students and their instructors. This learning module supplements traditional lecture and overhead presentations to offer a novel, nonthreatening, and entertaining introduction to neuropathology. The module is based on a ridiculous analogy between the human brain and the cauliflower. This module has been used with both underclassmen and more advanced health science undergraduate students and has produced enthusiastic student responses while deescalating both student and instructor anxiety. PMID- 11209562 TI - Who wants to be a physician? An educational tool for reviewing pulmonary physiology. AB - Traditional review sessions are typically focused on instructor-based learning. However, experts in the field of higher education have long recommended teaching modalities that incorporate student-based active-learning strategies. Given this, we developed an educational game in pulmonary physiology for first-year medical students based loosely on the popular television game show Who Wants To Be A Millionaire. The purpose of our game, Who Wants To Be A Physician, was to provide students with an educational tool by which to review material previously presented in class. Our goal in designing this game was to encourage students to be active participants in their own learning process. The Who Wants To Be A Physician game was constructed in the form of a manual consisting of a bank of questions in various areas of pulmonary physiology: basic concepts, pulmonary mechanics, ventilation, pulmonary blood flow, pulmonary gas exchange, gas transport, and control of ventilation. Detailed answers are included in the manual to assist the instructor or player in comprehension of the material. In addition, an evaluation instrument was used to assess the effectiveness of this instructional tool in an academic setting. Specifically, the evaluation instrument addressed five major components, including goals and objectives, participation, content, components and organization, and summary and recommendations. Students responded positively to our game and the concept of active learning. Moreover, we are confident that this educational tool has enhanced the students' learning process and their ability to understand and retain information. PMID- 11209563 TI - A visual aid for teaching ventilation-perfusion relationships. AB - To help students understand the concept of the ventilation-perfusion ratio (VA/Q) and the effects that VA/Q mismatching has on pulmonary gas exchange, a "sliding rectangles" visual aid was developed to teach VA/Q relationships. Adjacent rectangles representing "ventilation" and "perfusion" are slid past one another so that portions of the ventilation and perfusion rectangles are not touching, illustrating the concepts of dead-space ventilation (VD) and shunt flow (QS). The portion of the ventilation bar representing VD is further subdivided into anatomical and alveolar VD and used to show the effects of alveolar dead space on the PO2 (PAO2) and PCO2 of alveolar air (PACO2); movement away from the "ideal" point). Similarly, the portion of the perfusion bar representing QS is used to define anatomical and physiological shunts and the effect of shunts on the PO2 (PaO2) and PCO2 of arterial blood (PaCO2). The genesis of the PAO2-PaO2 (A-a) PO2 difference as well as the effects of VA/Q mismatching and diffusion abnormalities can all be discussed with this visual aid. This approach has greatly assisted some students in mastering this traditionally difficult area of respiratory physiology. PMID- 11209564 TI - The water-tower analogy of the cardiovascular system. AB - The cardiovascular system is a complex arrangement of hydraulic, yet living, components. The complexity of this system may make it difficult for students to see the "forest" instead of the "trees." To better explain the dynamics of cardiovascular function and control, an analogy has been drawn to the operation of a city water supply. In cities that use a water tower, fresh water is pumped up into the tower from a river or other source. The tower serves as a pressure reservoir for providing water to homes through a largely parallel arrangement of distribution pipes. Local homeowners control their own water usage through faucets, whereas the city maintains water pressure by monitoring the level in the tower. Key analogous points with the cardiovascular system are the heart as the city pump, the aorta as the water tower, arteries as parallel distribution pipes, and arterioles as faucets. Baroreceptor reflex control is discussed as well as such features as the capacitance role of veins, the skeletal muscle pump, and the competition between locally mediated vasodilation and sympathetically mediated vasoconstriction. Subjective student and peer evaluations have indicated that this analogy is effective in improving student comprehension of the cardiovascular system. PMID- 11209565 TI - Peer instruction improves performance on quizzes. AB - Peer instruction is a cooperative-learning technique that promotes critical thinking, problem solving, and decision-making skills. Benson's think-pair-share and Mazur's peer-instruction techniques are simple cooperative exercises that promote student's participation in class and increase student's interaction with each other and with the instructor in a large classroom. We borrowed concepts from Benson and Mazur and applied these concepts to enhance student involvement during the respiratory component of the medical physiology class. The medical physiology class consisted of 256 first-year medical students. The peer instruction technique was used for 10 classes. Each class of 50 min was divided into three or four short presentations of 12-20 min. Each presentation was followed by a one-question, multiple-choice quiz on the subject discussed. Questions ranged from simple recall to those testing complex intellectual activities. Students were given 1 min to think and to record their first answer. Subsequently, students were allowed 1 min to discuss their answers with their classmates and possibly correct their first response. The percentage of correct answers increased significantly (P < 0.05) after discussion for both recall and intellectual questions. These data demonstrate that pausing three to four times during a 50-min class to allow discussion of concepts enhanced the students level of understanding and ability to synthesize and integrate material. PMID- 11209566 TI - Effects of an applied supplemental course on student performance in elementary physiology. AB - The objective of this study was to determine whether students within a large (100 160 students) didactic lecture-based course, "Elementary Physiology" (EP), who were given an active-learning opportunity would perform better on objective examinations over EP material compared with their classroom peers who did not have the same active-learning experience. This was achieved by offering the EP students the option of taking a supplemental one credit hour discussion-based course, "Case Studies in Physiology" (CSP). Approximately 14% of the EP students opted for the CSP course. The format of CSP consisted of a one-hour-per-week discussion of applied problems based on the factual information presented in EP. On a subjective scale of 1 to 4, the CSP students felt that the course helped them to understand the EP material (3.5). This was reflected in the EP examination results for which the CSP students scored significantly higher compared with their non-CSP peers (81.1% vs. 75.7%; P < 0.05). These results indicate that when active-learning methods, such as discussion of applied problems, are used as a supplement to didactic lectures in physiology, performance on objective examinations of lecture material is improved. PMID- 11209567 TI - Misconceptions in physiology. PMID- 11209568 TI - Combination of didactic lecture with problem-based learning sessions in physiology teaching in a developing medical college in Nepal. AB - Physiology teaching as an essential part of medical education faces tremendous criticism regarding curriculum design, methods of implementation, and application of knowledge in clinical practice. In the traditional method of medical education, physiology is taught in the first year and involves little interdisciplinary interaction. The Manipal College of Medical Sciences, Pokhara, Nepal (affiliated with the Kathmandu Univ.) started in 1994 and adopted an integrated curriculum drawn along the lines of the student-centered, problem based, integrated, community-based, elective-oriented, and systematic (SPICES) medical curriculum. Here, physiology is taught for the first 2 yr of the 4.5-yr Bachelor of Medicine, Bachelor of Surgery course. Methodology adopted is as follows. For a particular topic, objectives are clearly defined and priority content areas are identified. An overview is given in a didactic lecture class to the entire batch of 100 students. Tutorial classes are conducted thereafter with smaller groups of students (25/batch) divided further into five subgroups of five students each. In these sessions, a problem is presented to the students as a focus for learning or as an example of what has just been taught. Each problem was accompanied with relevant questions to streamline the students' thought processes. A tutor is present throughout the session not as an instructor but as a facilitator of the learning process. A questionnaire sought students' opinion on the usefulness of this approach, relevance of the combination of problem-based learning (PBL) sessions and didactic lectures in understanding a particular topic and relating clinical conditions to basic mechanisms, and improvement of performance on the university final examination. The majority of the students opined that the combination of didactic lectures and PBL sessions was definitely beneficial regarding all the above-mentioned aspects of learning. The university results corroborated their opinion. Thus it may be considered that a judicious mixture of didactic lectures and PBL sessions is beneficial as a teaching module of physiology in medical schools. PMID- 11209569 TI - Managed care reform: state legislative trends in 1999. PMID- 11209570 TI - The ACS Capital Program: ensuring the care of the President. PMID- 11209571 TI - Are "impervious" surgical gowns really liquid-proof? PMID- 11209572 TI - PATH (physicians at teaching hospitals) audits. PMID- 11209573 TI - Gender and body mass index as related to the night-eating syndrome in obese outpatients. PMID- 11209574 TI - Male adolescents identify their weight gain practices, reasons for desired weight gain, and sources of weight gain information. PMID- 11209575 TI - Alternative health care education in dietetic training programs: a survey of perceived needs. PMID- 11209576 TI - Use and perceived effectiveness of strategies for enhancing food and nutrient intakes among elderly persons in long-term care. PMID- 11209577 TI - Position of the American Dietetic Association: food fortification and dietary supplements. AB - Wise food choices provide the necessary foundation for optimal nutrition. Science has not fully identified the specific chemical components that account for the benefits of healthy eating patterns. Selection of a variety of foods, using tools such as the USDA/HHS Dietary Guidelines for Americans and the USDA Food Guide Pyramid, is the best way to provide a desirable balance, without excessive intakes of macronutrients, micronutrients and other beneficial components of foods. Nevertheless, for certain nutrients and some individuals, fortification, supplementation, or both may also be desirable. Nutrient intakes from all these sources should be considered in dietary assessments, planning and recommendations. The recommendations of the National Academy of Sciences' Food and Nutrition Board provide a sound scientific basis for vitamin and mineral intakes. Intakes exceeding those recommendations have no demonstrated benefit for the normal, healthy population. Dietetics professionals should base recommendations for use of fortified foods or supplements on individualized assessment and sound scientific evidence of efficacy and safety. It is the position of the American Dietetic Association that the best nutritional strategy for promoting optimal health and reducing the risk of chronic disease is to wisely choose a wide variety of foods. Additional vitamins and minerals from fortified foods and/or supplements can help some people meet their nutritional needs as specified by science-based nutrition standards such as the Dietary Reference Intakes (DRI). PMID- 11209578 TI - Position of the American Dietetic Association: the impact of fluoride on health. AB - Fluoride is an important element for mineralization of body tissues. The use of topical and systemic fluoride for oral health has resulted in major reductions in dental caries and its associated disability. Fluoridation of public water supplies has been endorsed by over 90 professional health organizations as the most effective dental public health measure in existence. Still, about half of the US population fails to receive the maximum benefits possible from community water fluoridation and the use of fluoride products. Fluoride also plays a role in bone health. The role of high doses of fluoride for prevention of osteoporosis is undergoing active study and is considered experimental at this point. Dietetics professionals should routinely monitor and promote the use of systemic and topical fluorides, especially in children and adolescents. The American Dietetic Association strongly reaffirms its endorsement of the use of systemic and topical fluorides, including water fluoridation, at appropriate levels of intake, as an important public health measure. However, clients should be cautioned that experimental use of high intakes of fluoride should be avoided unless they are participating in clinical trials. PMID- 11209579 TI - Complexities beyond simple survival: challenges in providing care for HIV patients. PMID- 11209580 TI - MNT (medical nutrition therapy): an innovative employee-friendly benefit that saves. PMID- 11209581 TI - Effects of age on validity of self-reported height, weight, and body mass index: findings from the Third National Health and Nutrition Examination Survey, 1988 1994. AB - OBJECTIVE: To compare self-reported to measured heights and weights of adults examined in the Third National Health and Nutrition Examination Survey (NHANES III), and to determine to what extent body mass index (BMI) calculated from self reported heights and weights affects estimates of overweight prevalence compared with BMI calculated from measured values. DESIGN: A complex sample design was used in NHANES III to obtain a nationally representative sample of the US civilian, noninstitutionalized population. During household interviews, survey respondents were asked their height and weight. Trained health technicians subsequently measured height and weight using standardized procedures and equipment. SUBJECTS: The analytical sample consisted of 7,772 men and 8,801 women 20 years old and older. STATISTICAL ANALYSES PERFORMED: Only persons with measured and self-reported heights and weights were included in the analysis, and statistical sampling weights were applied. t Tests, Pearson product moment correlation coefficients, sensitivity, and specificity analyses were used to determine the validity of self-reported measurements and prevalence estimates of overweight, defined as BMI of 25 or greater. RESULTS: Age is an important factor in classifying weight, height, BMI, and overweight from self-reports. Statistically significant differences were found for the mean error (measured self-reported values) for height and BMI that were notably larger for older age groups. For example, the mean error for height ranged from 2.92 to 4.50 cm for women and from 3.06 to 4.29 cm for men, 70 years and older. Despite the high correlation between measured and self-reported data, the prevalence of overweight calculated from measured values was higher than that calculated from self reported values among older adults. When calculated with self-reported height, BMI was one unit lower than when calculated from measured height for persons > or = 70 years. Specificity was high but sensitivity decreased with increasing age cohorts. Regression equations are provided to determine actual height from self reported values for older adults. CONCLUSION/APPLICATIONS: Self-reported heights and weights can be used with younger adults, but they have limitations for older adults, ages > or = 60 years. In research studies and in clinical settings involving older adults, failure to measure height and weight can result in subsequent misclassification of overweight status. Therefore, registered dietitians are encouraged to obtained a measured weight and height using a calibrated scale and stadiometer. PMID- 11209582 TI - Is there a consumer backlash against the diet and health message? AB - OBJECTIVE: Anecdotal evidence exists that the public is becoming skeptical about nutrition messages. This article examines whether there is a backlash against dietary recommendations and whether it is associated with less healthful diets. DESIGN/PARTICIPANTS: Data are from a 1997-1998 Washington State random-digit-dial survey of 1,751 adults designed to monitor attitudes and behavior related to cancer risk and prevention. STATISTICAL ANALYSES: Responses to the nutrition backlash survey were weighted to reflect the Washington State population. Linear regression was used to examine associations of nutrition backlash with fat and fruit and vegetable intake. RESULTS: This survey did not find strong evidence that nutrition backlash was widespread. However, 70% of respondents thought that Americans are obsessed with the fat in their diet and that the government should not tell people what to eat. More than a quarter agreed with the statement that eating low-fat foods takes the pleasure out of eating. Nutrition backlash was associated with less healthful diets: individuals showing high backlash had a fat related diet habits score of 2.11 compared with a score of 1.73 among those showing low backlash (P for trend = .001), which corresponds to a difference of roughly 4 percentage points in percentage energy from fat. Individuals showing high backlash reported eating only 2.72 servings of fruits and vegetables per day, compared with 3.35 servings among those showing low backlash (P for trend = .001). APPLICATIONS/CONCLUSIONS: Nutrition professionals need to ensure that dietary recommendations are clear and positive to avoid the possibility that consumers may disregard nutrition messages entirely. PMID- 11209583 TI - The 30-second effect: an experiment revealing the impact of television commercials on food preferences of preschoolers. AB - OBJECTIVE: To examine whether televised food commercials influence preschool children's food preferences. DESIGN: In this randomized, controlled trial, preschool children viewed a videotape of a popular children's cartoon either with or without embedded commercials. Children were then asked to identify their preferences from pairs of similar products, one of which was advertised in the videotape with embedded commercials. Preschoolers' parents were interviewed to determine children's demographic characteristics and media use patterns. SUBJECTS: Forty-six 2- to 6-year-olds from a Head Start program in northern California. STATISTICAL ANALYSES: For demographic and media use characteristics, univariate data were examined and Student t and chi 2 tests were used to test for differences between the control and treatment groups. We calculated the Cochran Q statistic to assess whether the proportion of those choosing advertised food items was significantly higher in the treatment group than in the control group. RESULTS: Children exposed to the videotape with embedded commercials were significantly more likely to choose the advertised items than children who saw the same videotape without commercials (Qdiff = 8.13, df = 1, P < .01). CONCLUSIONS/APPLICATIONS: Even brief exposures to televised food commercials can influence preschool children's food preferences. Nutritionists and health educators should advise parents to limit their preschooler's exposure to television advertisements. Furthermore, advocates should raise the public policy issue of advertising and young children, especially given the recent epidemic of childhood obesity and the ever-changing media environment. PMID- 11209584 TI - Comparison of visual estimates of children's portion sizes under both shared plate and individual-plate conditions. AB - OBJECTIVE: This paper compares the accuracy of visual estimations of children's food intake in settings where several children eat together off 1 plate vs individual-plate eating scenarios. DESIGN: Eight trained observers were tested in their ability to estimate food portions consumed by children enacting common eating scenarios. Foods were categorized by food group and according to their presentation by individual-plate and shared-plate. Observed food weight estimates were compared to actual weights. SUBJECTS/SETTING: The 8 observers visually estimated 69 food portions of children eating alone and 26 portions where children were eating from a shared plate. This study was carried out in Sarlahi District, a rural, central lowland region of Nepal. STATISTICAL ANALYSES: Pearson's correlation coefficients were calculated to examine associations between estimated and actual weights. A fixed effects model was constructed to compare observers. RESULTS: Analyses revealed that observer estimates of food weights under field conditions were well correlated with actual weights for individual-plate (r = 0.89) and for shared-plate (r = 0.84) scenarios. Observers estimated food weights when children ate together on a shared plate less accurately than they did in settings where children ate alone. With the exception of 1 observer, observers did not differ significantly in their ability to estimate food weights. Accuracy of estimations was influenced by food weight with greater error associated with food quantities of less than 70 g. CONCLUSIONS: Visual estimation is a relatively accurate, valid method of assessing child food intake under rural field conditions, and the only method to obtain accurate information on dietary intake in regions where shared-plate eating is frequent. PMID- 11209585 TI - No differences in growth or body composition from age 12 to 24 months between toddlers consuming 2% milk and toddlers consuming whole milk. AB - OBJECTIVE: To determine whether consumption of 2% milk during the second year of life leads to reduced growth or lower percentage body fat compared with consumption of whole milk. SUBJECTS: Subjects were healthy toddlers who participated in a larger trial examining the effects of the timing of introduction of solid foods on growth. DESIGN: Three-day diet diaries, anthropometric measurements, and body composition determined by dual-energy x-ray absorptiometry were assessed at 12, 18, and 24 months of age. At age 12 months, the toddlers were similar in length, weight, percentage body fat, and total energy intake. From 12 to 24 months of age, milk consumption consisted of whole milk exclusively in one group (n = 23) and 2% milk exclusively in another group (n = 28). STATISTICAL ANALYSES: Differences between the 2 groups in anthropometric measurements, changes in anthropometric measurements, and dietary intakes were determined by Student t tests. Mean differences were considered significant at the P = .05 level. Data are presented as mean +/- standard deviation. RESULTS: Despite lower intakes of total fat and saturated fat in the 2% milk group, there were no differences in height, weight, and percentage body fat. Total energy intake was not reduced in the 2% milk group. APPLICATIONS: Reductions in total fat and saturated fat intake in toddlers can be achieved through the use of 2% milk without compromising growth. PMID- 11209586 TI - Breast-feeding practices among WIC participants in Hawaii. AB - OBJECTIVE: To describe breast-feeding practices and identify correlates of breast feeding among participants in the Hawaii Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) program. DESIGN: A cross-sectional survey. SUBJECTS/SETTING: We conducted structured, in-person interviews with 535 women at WIC clinics throughout Hawaii (95% response rate). The interview collected information on maternal characteristics and infant-feeding practices. STATISTICAL ANALYSES: Breast-feeding prevalence was examined by infant age and predictors of infant-feeding method were examined via bivariate tests and multivariable logistic regression analysis. Reported breast-feeding promotion efforts in health care settings outside of WIC were also examined. RESULTS: Most women (82%) attempted to breast-feed, albeit for short durations for many women; of the women who breast-fed in combination with formula feeding, 46% introduced formula within the first week after delivery. Significant predictors of breast-feeding initiation included previous breast-feeding experience, having a close relative or friend who breast-fed, multiparity, Asian/Pacific Island ethnicity (other than Filipino), and being foreign-born. Significant predictors of mixed feeding (vs exclusive breast-feeding) included working or attending school, age less than 20 years, Hawaiian/part Hawaiian or Filipino ethnicity, being Hawaiian-born, and residing in Oahu county. CONCLUSIONS: Although most women in this population initiated breast-feeding, formula was usually introduced at an early age. This study identified several factors associated with breast-feeding initiation and exclusive breast-feeding, factors that may prove useful for the development of appropriate interventions to promote these behaviors. PMID- 11209587 TI - Nutrition education in health professions programs: a survey of dental, physician assistant, nurse practitioner, and nurse midwifery programs. AB - OBJECTIVE: This study determined the perceived needs and curriculum recommendations for nutrition education, and expected competencies in nutrition of graduates, of predoctoral dental, physician assistant, nurse practitioner, and midwifery programs. SUBJECTS: Surveys were mailed to all dental schools (n = 54) and physician assistant (n = 95), nurse practitioner (n = 150), and certified nurse midwifery programs (n = 42) in the United States. Surveys were addressed to the program directors of physician assistant, nurse practitioner, and certified nurse midwifery programs and the associate or assistant dean of academic affairs of dental schools. DESIGN: A 4-page survey was designed and pilot-tested. The survey included questions on respondents perceptions of and recommendations for their programs in nutrition education and expected nutrition competence level of their graduates. A reminder postcard was mailed 2 weeks after the initial mailing to nonrespondents; a second survey was mailed to nonrespondents 1 month after the postcard mailing. STATISTICAL ANALYSES: Data were analyzed using JMP-IN software. Frequencies, and chi 2 analyses, Wilcoxon rank sum test, Pearson chi 2 test. RESULTS: The overall response rate was 80.7% (n = 276). Perceived needs for competence in nutrition varied by respondents. Most of the physician assistant nurse midwifery, and nurse practitioner program directors had similar perceptions of graduates' competence in nutrition. Dental school academic administrators differed significantly from the program directors about the perceived need for knowing how to counsel on a modified diet and how and when to refer to a registered dietitian. Time was the most important factor that would enhance provision of nutrition education in the programs. Computer-based programs were the most frequently requested education tool to enhance nutrition education. APPLICATIONS/CONCLUSIONS: The disciplines agreed that graduates of dental schools and physician assistant, nurse practitioner, and nurse midwifery programs need some level of competence in nutrition relative to their discipline. Registered dietitians involved in health professions education can play an active role in developing practice-based, time-sensitive, and flexible strategies for nutrition education of these health professions groups. PMID- 11209588 TI - Biased over- or under-reporting is characteristic of individuals whether over time or by different assessment methods. AB - Seven studies with repeated measurements of energy intake and/or nitrogen intake were examined to determine whether misreporting is characteristic of some persons or occurs randomly. Four of the studies were validated by doubly labeled water measurements of energy expenditure. Reporting validity was expressed as the ratio of energy intake to energy expenditure. Ratios were consistently below the expected value of 1.0 for some subjects and consistently above 1.0 for others, indicating characteristic reporting validity within subjects. Two year-long studies provided 4 to 12 measurements and a total number of days sufficient to measure individual habitual intake. Subjects mean energy intake to basal metabolic rate (BMR) ratios were < 1.35 in 45% and 47% and < 1.35 at every measurement in 25% of subjects. This indicated persistent underreporting over time, because 1.35 x BMR is the minimum energy expenditure compatible with a normally active lifestyle. Three of the studies used more than 1 assessment method (validated by doubly labeled water and/or urinary nitrogen excretion). There was a tendency for persons determined to be underreporters by 1 method to be also underreporters when tested by other methods. We conclude that biased over or underreporting is characteristic of some persons. Thus, repeat measurements do not necessarily provide valid measures of individual intake, extreme intakes may reflect under- and overreporting rather than true low or high intakes, and subjects most prone to reporting bias may be repeatedly misclassified in quantiles of the distribution. This presents a challenge to dietitians nutritionists, and statisticians both for the design of surveys and the handling of flawed data. PMID- 11209589 TI - Validation for MEDFICTS, a dietary assessment instrument for evaluating adherence to total and saturated fat recommendations of the National Cholesterol Education Program Step 1 and Step 2 diets. AB - MEDFICTS is a dietary assessment instrument designed to evaluate patient adherence to the National Cholesterol Education Program Step 1 and Step 2 diets. It provides a quick way to record food intake, portion size, and frequency of intake while focusing on foods that are the primary contributors of total fat, saturated fat, and cholesterol in the average American diet (i.e., Meats, Eggs, Dairy, Fried foods, fat In baked goods, Convenience foods, fats added at the Table and Snacks). MEDFICTS was validated in a pilot study using 16 computer analyzed sets of 4-day food records randomly selected from 7-day food records collected in the Diet Modification Clinic at Baylor College of Medicine, Houston, Tex). MEDFICTS correctly identified the 11 patients consuming a Step 1 diet, the 2 patients consuming the Step 2 diet and the 3 patients consuming an average American diet. Pearson correlation coefficients between MEDFICTS and the 4-day records were significant for percent energy from total fat (r = 0.81, P < .0002), saturated fat (r = 0.79, P < .0003), and cholesterol (r = 0.52, P < .039). Pearson correlation coefficients from 2 follow-up validation studies (3-day diet records [n = 22] through the Mary Imogene Bassett Research Institute, Cooperstown, NY, and a second study at the Diet Modification Clinic [n = 26]) also correlated significantly with percent energy from total fat (r = 0.56, P < .006; r = 0.71, P < .0001), saturated fat (r = 0.60, P < .003; r = 0.71, P < .0001), and approached significance for cholesterol intake (r = 0.54, P < .009; r = 0.39, P < .051) respectively. MEDFICTS is a quick, efficient tool that can be used in cardiovascular health screening, clinical practice, or research for the assessment of adherence to Step 1 or 2 diets. It can be self administered, and when reviewed with a dietitian, can provide an opportunity for nutrition education. PMID- 11209590 TI - Avoid unnecessary drug-related carbohydrates for patients consuming the ketogenic diet. AB - The ketogenic diet is intended for use in patients with epilepsy whose seizures are resistant to conventional drug therapy. It is a diet high in fat and low in carbohydrate and protein content, and is intended to produce ketosis from the incomplete metabolism of fats. It is safe and effective--many patients with severe, drug-resistant epilepsy show improvement. Limiting carbohydrate intake in patients to obtain the necessary ratio of fats to carbohydrates and protein requires careful planning and, in children, parental involvement. Although the ketogenic diet is professionally planned, an unrecognized source of carbohydrates is prescription and over-the-counter medications. If the carbohydrate content of medications is overlooked, ketosis can be inhibited with potential loss of seizure control occurring. Thus, it is essential for care providers and parents to know the carbohydrate content of medications, including not only the typical sugar content, but also the content of reduced carbohydrate (e.g., glycerin). From information supplied by drug manufacturers, we determined the carbohydrate content of commonly used medications. By knowing the carbohydrate content of these often used medications, the additional carbohydrate content of the medications can be taken into account and adjustments can be made in the ketogenic diet. PMID- 11209591 TI - The social ecology of health: leverage points and linkages. AB - The authors demonstrate the usefulness of social ecology theory for improving the treatment and prevention of poor health. The social ecology of health, unlike the topics of previous triptychs in Behavioral Medicine, is a field without a clearly defined body of literature. We begin with an overview of the ecological perspective and ecological theory as outlined by Bronfenbrenner and colleagues, provide examples of how ecological concepts have been demonstrated to influence health, and discuss how these concepts can be used by health professionals. We present a heuristic model illustrating leverage points and linkages (i.e., socioeconomic status, family, work, and school), for health, and we conclude with a consideration of the benefits of social ecology to health professionals and a summary of the limitations of the ecological model. PMID- 11209592 TI - Group interventions and the limits of behavioral medicine. AB - A wide range of interventions has been devised to address health hazards in the social and physical environment. The authors propose a 2-dimensional matrix to organize these interventions. The timing of interventions is divided into 4 stages: preventing exposure to hazard (proactive primary prevention), preventing symptoms from appearing (reactive primary prevention), preventing early symptoms from becoming chronic or leading to disease (secondary prevention), and managing the disease (tertiary prevention). The level at which the intervention is targeted is divided into 2 categories: micro (individual or family) and macro (more aggregate social level). Large-scale interventions such as media campaigns can target either individual health behaviors (microlevel) or the environment (macrolevel). This typology is illustrated with interventions designed to prevent or ameliorate the health consequences of adverse employment changes such as job loss. The analysis concludes that behavioral medicine and public health approaches are differentially suited to different intervention types. PMID- 11209593 TI - Social ecology and behavioral medicine: implications for training, practice, and policy. AB - Social ecology offers a conceptual framework for understanding the etiology of multiple health problems and a basis for designing broad-gauge educational, therapeutic, and policy interventions to enhance personal and community well being. Implications of social ecology for behavioral medicine are considered in relation to the development of diagnostic and therapeutic practices, professional training programs, and health policies implemented at municipal, state, and national levels. By influencing the training and practices of healthcare professionals and the decisions of corporate and community leaders, behavioral medicine can expand the scope and impact of future interventions beyond the health gains achievable through provision of direct services to patient populations. Potential barriers to establishing ecologically based health programs and policies and directions for research at the interface of behavioral medicine, social ecology, and public health are discussed. PMID- 11209594 TI - Psychological stress may induce increased humoral and decreased cellular immunity. AB - Stress alters immune function and affects different immune cell populations in different ways. The authors examined whether psychological stress has different effects on the production of macrophage, T-helper 1(Th1) cell, and T-helper 2(Th2) cell-derived cytokines. Forty-two college students were recruited and their blood was sampled on the day they were to take a stressful academic examination and again 4 weeks after the examination. The stress from the academic examination significantly increased IL-1 beta, IL-6, and IL-10 and decreased IFN gamma production. These findings suggest that examination stress may increase Th2 cell-mediated humoral immunity and macrophage activities and may decrease Th1 cell-mediated cellular immunity. PMID- 11209595 TI - Crystal structure of F2NO+AsF6- and method for extracting meaningful geometries from oxygen/fluorine disordered crystal structures. PMID- 11209596 TI - A Baker-Figgis isomer of conventional sandwich polyoxometalates. H2Na14[FeIII2(NaOH2)2(P2W15O56)2], a diiron catalyst for catalytic H2O2-based epoxidation. PMID- 11209597 TI - Dinuclear and heteropolynuclear complexes containing Mo2(4+) units. AB - The quadruply bonded compound Mo2(DpyF)4 (1), where DpyF- is the anion of N,N' di(2-pyridyl)formamidine, has been prepared by ligand substitution reactions of Mo2(OOCCF3)4 and either the neutral ligand, HDpyF, at ambient temperature or its lithium salt, LiDpyF, under refluxing conditions. An X-ray structural analysis shows that 1 has a paddlewheel structure with a [symbol: see text] distance of 2.1108(6) A. Reaction of 1 with CoCl2 in methanol produces the paramagnetic compound [Mo2Co(DpyF)4][CoCl4].2MeOH (2). The Co(II) atom in the cation [Mo2Co(DpyF)4]2+ resides on a low-spin hexacoordinate environment (S = 1/2) with a Co...Mo separation of 2.979(6) A, suggesting there is no direct bonding interaction between the Co and Mo atoms. The Mo-Mo distance of 2.1096(5) A is similar to that in 1. Reaction of 1 and CuCl in methanol yields [Mo2Cu4(DpyF)4Cl2][CuCl2]2.2MeOHxEt2O (3). In the cation there are two copper atoms on each side of the Mo2 core. Each is coordinated to two pyridyl nitrogen atoms of the cis DpyF- ligands and loosely bridged to the other by a chloride ion. As a result, the Cu(I) atoms are not aligned with the Mo2 unit. The Cu to Mo separations are in the range 3.003(1)-3.015(1) A, and the Mo-Mo distance of 2.127(1) A is comparable to those in 1 and 2. PMID- 11209598 TI - Di-tert-butyl phosphate complexes of cobalt(II) and zinc(II) as precursors for ceramic M(PO3)2 and M2P2O7 materials: synthesis, spectral characterization, structural studies, and role of auxiliary ligands. AB - Reaction of the metal acetates M(OAc)2xH2O with di-tert-butyl phosphate (dtbp-H) (3) in a 4:6 molar ratio in methanol or tetrahydrofuran followed by slow evaporation of the solvent results in the formation of metal phosphate clusters [M4(mu 4-O)(dtbp)6] (M = Co (4, blue); Zn (5, colorless)) in nearly quantitative yields. The same reaction, when carried out in the presence of a donor auxiliary ligand such as imidazole (imz) and ethylenediamine (en), results in the formation of octahedral complexes [M(dtbp)2(imz)4] (M = Co (6); Ni (7); Zn (8)) and [Co(dtbp)2-(en)2] (9). The tetrameric clusters 4 and 5 could also be converted into mononuclear 6 and 8; respectively, by treating them with a large excess of imidazole. The use of slightly bulkier auxiliary ligand 3,5-dimethylpyrazole (3,5 dmp) in the reaction between cobalt acetate and 3 results in the isolation of mononuclear tetrahedral complex [Co(dtbp)2(3,5-dmp)2] (10) in nearly quantitative yields. Perfectly air- and moisture-stable samples of 4-10 were characterized with the aid of analytical, thermoanalytical, and spectroscopic techniques. The molecular structures of the monomeric pale-pink compound 6, colorless 8, and deep blue 10 were further established by single-crystal X-ray diffraction studies. Crystal data for 6: C28H52CoN8O8P2, a = 8.525(1) A, b = 9.331(3) A, c = 12.697(2) A, alpha = 86.40(2) degrees, beta = 88.12(3) degrees, gamma = 67.12(2) degrees, triclinic, P1, Z = 1. Crystal data for 8: C28H52N8O8P2Zn, a = 8.488(1) A, b = 9.333(1) A, c = 12.723(2) A, alpha = 86.55(1) degrees, beta = 88.04(1) degrees, gamma = 67.42(1) degrees, triclinic, P1, Z = 1. Crystal data for 10: C26H52CoN4O8P2, a = b = 18.114(1) A, c = 10.862(1) A, tetragonal, P4(1), Z = 4. The Co2+ ion in 6 is octahedrally coordinated by four imidazole nitrogens which occupy the equatorial positions and oxygens of two phosphate anions on the axial coordination sites. The zinc derivative 8 is isostructural to the cobalt derivative 6. The crystal structure of 10 reveals that the central cobalt atom is tetrahedrally coordinated by two phosphate and two 3,5-dmp ligands. In all structurally characterized monomeric compounds (6, 8, and 10), the dtbp ligand acts as a monodentate, terminal ligand with free P=O phosphoryl groups. Thermal studies indicate that heating the samples at 171 (for 4) or 93 degrees C (for 5) leads to the loss of twelve equivalents of isobutene gas yielding carbon-free [M4(mu 4-O)(O2P(OH)2)6], which undergoes further condensation by water elimination to yield a material of the composition Co4O19P6. This sample of 4 when heated above 500 degrees C contains the crystalline metaphosphate Co(PO3)2 along with amorphous pyrophosphate M2P2O7 in a 2:1 ratio. Similar heat treatment on samples 6-8 results in the exclusive formation of the respective metaphosphates Co(PO3)2, Ni(PO3)2, and Zn(PO3)2; the tetrahedral derivative 10 also cleanly converts into Co(PO3)2 on heating above 600 degrees C. PMID- 11209599 TI - Topologically constrained manganese(III) and iron(III) complexes of two cross bridged tetraazamacrocycles. AB - A family of Mn3+ and Fe3+ complexes of 4,11-dimethyl-1,4,8,11 tetraazabicyclo[6.6.2]hexadecane (1) and 4,10-dimethyl-1,4,7,10 tetraazabicyclo[5.5.2]tetradecane (2) has been prepared by the chemical oxidation of the divalent manganese and iron analogues. The ligands are ethylene cross bridged tetraazamacrocycles derived from cylam and cyclen, respectively. The synthesis and characterization of these complexes, including X-ray crystal structure determinations, are described. The structural evidence demonstrates that the tetradentate ligands enforce distorted octahedral geometries on the metal ions, with two cis sites occupied by labile ligands. Magnetic measurements reveal that the complexes are high spin with typical magnetic moments. Cyclic voltammetry shows reversible redox processes for the Fe3+/Fe2+ couples of the iron(III) complexes, while Mn3+/Mn2+ and Mn4+/Mn3+ couples were observed for the complexes with manganese(III). The manganese chemistry of 1 was studied in depth. The dichloro manganese(III) cation of 1 undergoes facile ligand substitution reactions at the labile, monodentate sites, for example substituting azide for chloride ligands. Air oxidation of the dichloro complex of Mn (1)2+ in basic solution does not give the expected mu-oxo dimeric product common to manganese. Instead, an unusual manganese(III)-OH complex has been isolated from this reaction and structurally characterized. A similar reaction under slightly different conditions gives a putative MnIII(OH)2 complex that metathesizes to MnIII(OMe)2 upon recrystallization from methanol. PMID- 11209600 TI - Imprinting structural information from a GpG ligand into the configuration of a chiral diamine ligand through second-sphere communication in platinum(II) complexes. AB - Cisplatin forms the cis-Pt(NH3)2(d(GpG)) cross-link with DNA. We have recently created novel d(GpG) conformations by using "retro models" (complexes having bulky carrier ligands designed to slow d(GpG) dynamic motion). Our results define four conformer classes: HH1, HH2, delta HT1, and delta HT2, with a head-to-head or head-to-tail base orientation and a phosphodiester backbone with a normal (1) or opposite (2) propagation direction. Moreover, each G residue can be syn or anti, and the base canting can be left-handed (L) or right-handed (R). Thus, 32 variants of cis-Pt(NH3)2(d(GpG)) are conceivable, but the adduct is too dynamic to study. Thus far, by using retro models, we have obtained evidence for five variants with d(GpG) but only four with GpG. We therefore selected Me2DAPPt(GpG) complexes for study by 1H and 31P NMR spectroscopy, CD spectroscopy, and molecular mechanics and dynamics (MMD) calculations. Coordinated Me2DAP (N,N' dimethyl-2,4-diaminopentane) has N, C, C, N chiral centers designated, for example, as R,R,R,R. This ligand has greater flexibility and more readily inverted N centers than ligands used previously in GpG retro models. One goal was to determine whether the GpG ligand can control the configuration of a carrier ligand. (R,R,R,R)-Me2DAPPt(GpG) forms the anti, anti HH1 R variant almost exclusively. Equal populations of the two possible linkage isomers of (S,R,R,R) Me2DAPPt(GpG) are formed, both favoring the anti, anti HH1 R, variant; however, the isomer with the 5'-G cis to the S nitrogen has sharper signals, suggesting that interligand interactions are more favorable. Indeed, this linkage isomer was the major product of isomerization when (R,R,R,R)-Me2DAPPt(GpG) was kept at pH approximately 9.5 to allow N center equilibration. Steric clashes between the Me2DAP C-Me groups and the G O6 atoms found by MMD calculations appear to disfavor the HH1 conformer of (S,S,S,S)-Me2DAPPt(GpG) and (S,S,S,R)-Me2DAPPt(GpG) complexes. These two complexes have a significant population of the anti, syn delta HT1 conformer, as indicated by broad 1H NMR signals and by 31P NMR and CD data. Equilibration of (S,S,S,R)-Me2DAPPt(GpG) at pH 9.5 leads to a mixture of (S,S,S,S)-Me2DAPPt(GpG) and at least one isomer of (S,S,S,R)-Me2DAPPt(GpG). Thus, second-sphere communication (hydrogen bonding and steric interligand interactions) influences both GpG conformation and Me2DAP configuration. PMID- 11209601 TI - Cisplatin-DNA cross-link retro models with a chirality-neutral carrier ligand: evidence for the importance of "second-sphere communication". AB - We employ retro models, cis-PtA2G2 (A2 = a diamine, G = guanine derivative), to assess the cross-linked head-to-head (HH) form of the cisplatin-DNA d(GpG) adduct widely postulated to be responsible for the anticancer activity. Retro models are designed to have minimal dynamic motion to overcome problems recognized in models derived from cisplatin [A2 = (NH3)2]; the latter models are difficult to understand due to rapid rotation of G bases about the Pt-N7 bond in solution and the dominance of the head-to-tail (HT) form in the solid. Observation of an HH form is unusual for cis-PtA2G2 models. Recently, we found the first HH forms for a cis-PtA2G2 model with A2 lacking NH groups in a study of new Me2ppzPtG2 models. (Me2ppz, N,N'-dimethylpiperazine, has inplane bulk which reduces dynamic motion by clashing with the G O6 as the base rotates into the coordination plane from the ground state position approximately perpendicular to this plane G = 5'-GMP and 3'-GMP.) The finding of an HH form (albeit in a mixture with HT forms) with both G H8 signals unusually downfield encouraged us to study additional Me2ppzPtG2 analogues in order to explain the unusual spectral features and to identify factors that influence the relative stability of HT and HH forms. Molecular modeling techniques suggest HH structures with the H8's close to the deshielding region of the z axis of the magnetically anisotropic Pt atom, explaining the atypical shift pattern. When G = 1-Me-5'-GMP, we obtained NMR evidence that the HH rotamer has a high abundance (34%) and that the three rotamers have nearly equal abundance. These findings and the observation that the relative HT distributions varied little or not at all as a function of pH when G = Guo, 1-MeGuo, or 1-Me-5'-GMP are consistent with two of our earlier proposals concerning phosphate groups in HT forms of cis-PtA2(GMP)2 complexes. We proposed that a G phosphate group can form hydrogen bonds with the cis G N1H ("second sphere" communication) and (for 5'-phosphate) A2 NH groups. The new results with 1-Me-5'-GMP led us to propose a new role for a 5'-phosphate group; it can also favor the HH form by counteracting the natural preference for the G bases to adopt an HT orientation. Finally, the HH form was also sufficiently abundant to allow observation of a distinct 195Pt NMR signal (downfield of the resonance observed for the HT forms) for several complexes. This is the first report of an HH 195Pt NMR signal for cis-PtA2G2 complexes. PMID- 11209602 TI - Synthesis and characterization of iridium 1,3,5-triaza-7-phosphaadamantane (PTA) complexes. X-ray crystal and molecular structures of [Ir(PTA)4(CO)]Cl and [Ir(PTAH)3(PTAH2)(H)2]Cl6. AB - The first 1,3,5-triaza-7-phosphaadamantane (PTA) ligated iridium compounds have been synthesized. The reaction of PTA with [Ir(COD)Cl]2 (COD = 1,5 cyclooctadiene) under a CO atmosphere produces an inseparable mixture of [Ir(PTA)3(CO)Cl] (1) and the PTA analogue of Vaska's compound, [Ir(PTA)2(CO)Cl] (2). Compound 1 and [Ir(PTA)4(CO)]Cl (3) were prepared via ligand substitution reactions of PTA with Vaska's compound, trans-Ir(PPh3)2(CO)Cl, in absolute and 95% ethanol, respectively. Complex 3 crystallizes in the orthorhombic space group Pbca with a = 20.3619(4) A, b = 14.0345(3) A, c = 24.1575(5) A, and Z = 8. Single crystal X-ray diffraction studies show that 3 has a trigonal bipyramidal structure in which the CO occupies an axial position. This is the first crystallographically characterized [IrP4(CO)]+ complex in which the CO is axially ligated. Compound 1 was converted into 3 by ligand substitution with 1 equiv of PTA in water. Interestingly, the reaction of 3 with excess NaCl did not result in the production of 1, but instead the formation of the dichloro species, [Ir(PTAH)2(PTA)2Cl2]Cl3 (4) (PTAH = protonated PTA). Dissolution of 1 or 3 in dilute HCl produced 4 and a dihydrido species, [Ir(PTAH)4(H)2]Cl5 (5), which were readily separated by inspection due to their different crystal habits. Compound 5 crystallizes in the triclinic space group P1 with a = 12.4432(9) A, b = 12.5921(9) A, c = 16.3231(12) A, alpha = 76.004(1) degrees, beta = 71.605(1) degrees, gamma = 69.177(1) degrees, and Z = 2. Complex 5 exhibits a distorted octahedral geometry with two hydride ligands in a cis configuration. A rationale consistent with these reactions is presented by consideration of the steric and electronic properties of the PTA ligand. PMID- 11209603 TI - Connecting pairs of dimetal units to form molecular loops. AB - Four compounds consisting of molecular loops formed from two quadruply bonded Mo2(DAniF)2 (DAniF = N,N'-di-p-anisylformamidinate) units linked by two dicarboxylate anions have been prepared in high purity and essentially quantitative yields. These compounds have been characterized by crystallography and NMR spectroscopy and display electrochemical behavior dependent on the nature of the dicarboxylate anion. However, the electronic communication between the two Mo2(4+) units is not strong. As denoted by the dicarboxylate linkers, the compounds are malonate, 1, 1,4-phenylendiacetate, 2, homophthalate, 3, and trans cyclopentane-1,2-dicarboxylate, 4. PMID- 11209604 TI - Supramolecular squares with Mo2(4+) corners. AB - Seven complexes obtained by reacting the quadruply bonded complex [Mo2(cis DAniF)2(CH3CN)4](BF4)2 (DAniF = N,N'-di-p-anisylformamidinate) and (Bun4N+)2(Carb2-), where Carb2- is a dicarboxylate anion, have been found to have a ratio of dimetal unit to dicarboxylate of 1:1. As noted by the carboxylate linker, the compounds are oxalate, 1, fumarate, 2, ferrocene dicarboxylate, 3, 4,4'-biphenyldicarboxylate, 4, acetylenedicarboxylate, 5, tetrafluorophthalate, 6, and carborane dicarboxylate, 7. Structural characterization of 1-4 revealed a square of dimolybdenum units linked by the dicarboxylate anions, each having an interstice capable of accommodating specific solvent molecules. Results of NMR studies of all seven compounds are consistent with the presence of a highly symmetrical structure. These compounds display a rich electrochemical behavior that is affected by the nature of the carboxylate group. PMID- 11209605 TI - Terpsichorean movements of pentaammineruthenium on pyrimidine and isocytosine ligands. AB - Pentaammineruthenium moves on ambidentate nitrogen heterocycles by both rotation and linkage isomerization, which may affect the biological activity of potential ruthenium metallopharmaceuticals. The rapid rotation rates of [(NH3)5RuIII] coordinated to the exocyclic nitrogens of isocytosine (ICyt) and 6 methylisocytosine (6MeICyt) have been determined by 1H NMR. Since these rotamers can be stabilized by hydrogen bonding between the coordinated ammines and the N1 and N3 endocyclic nitrogens, rotamerization is under pH control. Spectrophotometrically (UV-vis) measured pKa values for the two endocyclic sites for the ICyt complex are 2.78 and 9.98, and for 6MeICyt are 3.06 and 10.21, which are probably weighted averages for ionization from N3 and N1, respectively. Activation parameters for the rotamerizations were determined by variable temperature NMR at pKa1 < pH < pKa2 for the complexes with (ICyt-kappa N2)-, (6MeICyt kappa N2)-, and 2AmPym kappa N2. For [(6MeICyt kappa N2)(-) (NH3)5RuIII]2+, delta H* = 1.6 kcal/mol, delta S* = -37 cal/mol K, and Ea = 2.2 kcal/mol. Due to strong RuIII-N pi-bonding, the activation enthalpies are approximately 10 kcal lower than the expected values for the free ligands. Rotameric structure is correlated with pKa values, pH-dependent reduction potentials, and 1H NMR parameters. Linkage isomers of [(2AmPym)(NH3)5Ru]n+ are reported in which RuII is coordinated to the endocyclic nitrogen (N1) and RuIII to the exocyclic nitrogen (N2). The rate constant for the kappa N2-->kappa N1 isomerization as part of an ECE mechanism is 3.9 s-1 at pH 3. The pH dependence of the acid-catalyzed hydrolysis of [(2AmPym kappa N1)(NH3)5Ru]2+ is determined. PMID- 11209606 TI - Syntheses and characterizations of metal complexes derived from cis,cis-1,3,5 triaminocyclohexane-N,N',N"-triacetic acid. AB - A convenient six-step procedure is developed to routinely prepare the hexadentate ligand cis,cis-1,3,5-triaminocyclohexane-N,N',N"-triacetic acid (H3tachta) as an HCl salt. Complexes of gallium(III) and indium(III), [Ga(tachta)] and [In(tachta)], are synthesized from the reactions of the ligand and the corresponding metal precursors. Copper(II), palladium(II), and cobalt(II) complexes, [Cu(Htachta)], [Pd(Htachta)], and [Co(Htachta)], are obtained from the reactions of H3tachta with the corresponding metal chlorides. The structures of H3tachta.3HCl.2H2O (C12H28Cl3N3O8) and [Ga(tachta)] (C12H18GaN3O6) are characterized. The crystal of H3tachta.3HCl.2H2O is monoclinic, of the space group P2(1)/c, with a = 15.1688(4) A, b = 8.4708(2) A, c = 15.9408(2) A, beta = 108.058(1) degrees, and Z = 4; that of [Ga(tachta)] is cubic, of space group Pa3, with a = 14.0762(1) A and Z = 8. The gallium atom of [Ga(tachta)] is six coordinated in the solid state, and the complex assumes a pseudooctahedronal geometry with the completely deprotonated hexadentate ligand encapsulating the metal ion. PMID- 11209607 TI - Atom transfer reactions of (TTP)Ti(eta 2-3-hexyne): synthesis and molecular structure of trans-(TTP)Ti[OP(Oct)3]2. AB - Atom and group transfer reactions were found to occur between heterocumulenes and (TTP)Ti(eta 2-3-hexyne), 1 (TTP = meso-5,10,15,20-tetra-p-tolylporphyrinato dianion). The imido derivatives (TTP)Ti=NR (R = iPr, 2; tBu, 3) were produced upon treatment of complex 1 with iPrN=C=NiPr, iPrNCO, or tBuNCO. Reactions between complex 1 and CS2, tBuNCS, or tBuNCSe afforded the chalcogenido complexes, (TTP)Ti=Ch (Ch = Se, 4; S, 5). Treatment of complex 1 with 2 equiv of PEt3 yielded the bis(phosphine) complex, (TTP)Ti(PEt3)2, 6. Although (TTP)Ti(eta 2-3-hexyne) readily abstracts oxygen from epoxides and sulfoxides, the reaction between 1 and O=P(Oct)3 did not result in oxygen atom transfer. Instead, the paramagnetic titanium(II) derivative (TTP)Ti[O=P(Oct)3]2, 7, was formed. The molecular structure of complex 7 was determined by single-crystal X-ray diffraction: Ti-O distance 2.080(2) A and Ti-O-P angle of 138.43(10) degrees. Estimates of Ti=O, Ti=S, Ti=Se, and Ti=NR bond strengths are discussed. PMID- 11209608 TI - Syntheses, structures, and luminescence of novel lanthanide complexes of tripyridylamine, N,N,N',N'-tetra(2-pyridyl)-1,4-phenylenediamine and N,N,N',N' tetra(2-pyridyl)biphenyl-4,4'-diamine. AB - Two novel blue luminescent bridging ligands N,N,N',N'-tetra(2-pyridyl)-1,4 phenylenediamine (tppd) and N,N,N',N'-tetra(2-pyridyl)-1,1-biphenyl-4,4'-diamine (tpbpd) have been synthesized. Several novel lanthanide complexes containing 2,2',2"-tripyridylamine (2,2',2"-tpa), 2,2',3"-tpa, tppd, or tpbpd ligands have been synthesized and characterized structurally, which include Pr(hfa)3(2,2',2" tpa), I, Ln(tmhd)3(2,2',3"-tpa), 2 (Ln = Dy, 2a; Eu, 2b; Tb, 2c; Sm, 2d), [Eu(tmhd)3][Pr(hfa)3](2,2',3"-tpa), 3, [Pr(hfa)3]2(tppd), 4, and [Ln(hfa)3]2(tpbpd), 5, where Ln = Pr (5a), Eu (5b), tmhd = 2,2,6,6-tetramethyl 3,5-heptanedionato, and hfa = hexafluoroacetylacetonate. The Dy(III), Eu(III), and Tb(III) complexes display a bright photoluminescence, which can be achieved by either a direct excitation process or an indirect excitation process. Compounds 2a-2d can be sublimed readily. PMID- 11209609 TI - Dinuclear calcium complex with weakly NH...O hydrogen-bonded sulfonate ligands. AB - The novel intramolecularly NH...O hydrogen-bonded Ca(II)-aryl sulfonate complex, [Ca2(SO3-2-t-BuCONHC6H4)2(H2O)4]n(2-t-BuCONHC6H4SO3)2n (1), sulfonate anion, (HNEt3)(SO3-2-t-BuCONHC6H4) (2a), (PPh4)(SO3-2-t-BuCONHC6H4) (2b), (n-Bu4N)(SO3-2 t-BuCONHC6H4) (2c), and sulfonic acid, 2-t-BuCONHC6H4SO3H (3), were synthesized. The structures of 1, 2a, and 2b depict the presence of the formation of NH...O hydrogen bonds between the amide NH and S-O oxygen for a series of compounds as determined by IR and 1H NMR analyses both in the solid state and in the solution state. Thus, the NH...O hydrogen bonds with neutral amide groups are available for investigation of the electronic state of the O- anion. The combined data from the IR and 1H NMR spectra indicate that the sulfonic acid, sulfonate anion, and Ca(II) complex have a substantially weak intramolecular NH...O hydrogen bond between the SO3 oxygen and amide NH. In the detailed comparison with the intense NH...O hydrogen bonds for the carboxylate, weak NH...O hydrogen bonds for sulfonate is due to the strong conjugation of the SO3- group with the lower nucleophilicity. PMID- 11209610 TI - Excision of zirconium iodide clusters from highly cross-linked solids. AB - Highly cross-linked cluster precursors KZr6I14B, Zr6I12B, KZr6I14C, and Zr6I12C were, successfully excised in deoxygenated water, and the resulting red aqueous solutions of clusters exhibit better kinetic stability with respect to decomposition than their chloride and bromide analogues. On traversing the Cl-->I series, NMR measurements show increasing deshielding of the interstitial atoms (Z = B, C) in Zr6ZX12 clusters and cyclic voltammetry reveals increasingly positive reduction potentials for the [(Zr6BX12)(H2O)6]+ ions. Several new cluster complexes have been crystallized from aqueous or methanolic solutions. Crystallographic data for these compounds are as follows: [(Zr6BI12)(H2O)6]Ix11.7(H2O) (1), triclinic, P1, a = 10.2858(7) A, b = 11.3045(8) A, c = 20.808(1) A, alpha = 77.592(1) degrees, beta = 79.084(1) degrees, gamma = 77.684(1) degrees, Z = 2; [(Zr6BI12)]+[I(CH3OH)6]- (2), hexagonal, R3, a = 17.706(1) A, c = 13.910(1) A, Z = 3, [(Zr6CI12)(H2O)6]I(2).4(H2O) (3), triclinic, P1, a = 10.1566(5) A, b = 10.4513(5) A, c = 10.7549(6) A, alpha = 117.552(1) degrees, beta = 96.443(1) degrees, gamma = 96.617(1) degrees, Z = 1. PMID- 11209611 TI - Pressure dependence of peroxynitrite reactions. Support for a radical mechanism. AB - Activation volumes (delta V++) have been determined for several reactions of peroxynitrite using the stopped-flow technique. Spontaneous decomposition of ONOOH to NO3- in 0.15 M phosphate, pH 4.5, gave delta V++ = 6.0 +/- 0.7 and 14 +/ 1.0 cm3 mol-1 in the presence of 53 microM and 5 mM nitrite ion, respectively. One-electron oxidations of Mo(CN)8(4-) and Fe(CN)6(4-), which are first order in peroxynitrite and zero order in metal complex, gave delta V++ = 10 +/- 1 and 11 +/- 1 cm3 mol-1, respectively, at pH 7.2. The limiting yields of oxidized metal complex were found to decrease from 61 to 30% of the initially added peroxynitrite for Mo(CN)8(3-) and from 78 to 47% for Fe(CN)6(3-) when the pressure was increased from 0.1 to 140 MPa. The bimolecular reaction between CO2 and ONOO- was determined by monitoring the oxidation of Fe(CN)6(4-) by peroxynitrite in bicarbonate-containing 0.15 M phosphate, pH 7.2, for which delta V++ = -22 +/- 4 cm3 mol-1. The Fe(CN)6(3-) yield decreased by approximately 20% upon increasing the pressure from atmospheric to 80 MPa. Oxidation of Ni(cyclam)2+ by peroxynitrite, which is first order in each reactant, was characterized by delta V++ = -7.1 +/- 2 cm3 mol-1, and the thermal activation parameters delta H++ = 4.2 +/- 0.1 kcal mol-1 and delta S++ = -24 +/- 1 cal mol-1 K-1 in 0.15 M phosphate, pH 7.2. These results are discussed within the context of the radical cage hypothesis for peroxynitrite reactivity. PMID- 11209612 TI - In situ NMR observation of mono- and binuclear rhodium dihydride complexes using parahydrogen-induced polarization. AB - Starting from the binuclear complex [RhCl(NBD)]2 (NBD = 2,5-norbornadiene) in the presence of the phosphines L = PMe3, PMe2Ph, PMePh2, PEt3, PEt2Ph, PEtPh2, or P(n butyl)3, various mononuclear dihydrides of the type Rh(H)2CIL3, i.e., those of the homogeneous hydrogenation catalysts RhCIL3, have been obtained upon addition of parahydrogen, and their 1H NMR spectra have been investigated using parahydrogen-induced polarization (PHIP). Furthermore, the two binuclear complexes (H)(Cl)Rh(PMe3)2(mu-Cl)(mu-H)Rh(PMe3) and (H)(Cl)Rh(PMe2Ph)2(mu-Cl)(mu H)Rh(PMe2Ph) have been detected and characterized by means of this in situ NMR method. Analogous complexes with trifluoroacetate instead of chloride, i.e., Rh(H)2(CF3COO)L3, have been generated in situ starting from Rh(NBD)(acac) in the presence of trifluoroacetic acid in combination with the phosphines L = PPh3, PEt2Ph, PEt3, and P(n-butyl)3, and their 1H NMR parameters have been determined. PMID- 11209613 TI - Lithium halide adducts of imidotellurium(IV) ligands: synthesis and X-ray structures of [Li(THF)2L](mu 3-I)[LiI(L)] [L = tBuNTe(mu-NtBu)2TeNtBu] and [(THF)3Li3(mu 3-I)(Te(NtBu)3)]. AB - The reaction of the chelating ligand tBuNTe(mu-NtBu)2TeNtBu (L) with LiI in THF yields [Li(THF)2L](mu 3-I)[LiI(L)] (3). This complex is also formed by the attempted oxidation of [Li2Te(NtBu)3]2 with I2. An X-ray analysis of 3 reveals that the tellurium diimide dimer acts as a chelating ligand toward (a) [Li(THF)2]+ cations and (b) a molecule of LiI. An extended structure is formed via weak Te...I interactions [3.8296(7)-3.9632(7) A] involving both mu 3-iodide counterions and the iodine atoms of the coordinated LiI molecules. Crystal data: 3, triclinic, space group P1, a = 10.1233(9) A, b = 15.7234(14) A, c = 18.8962(17) A, alpha = 86.1567(16) degrees, beta = 84.3266(16) degrees, gamma = 82.9461(16) degrees, V = 2965.8(5) A3, Z = 2. The oxidation by air of [Li2Te(NtBu)3]2 in toluene produces the radical (Li3[Te(NtBu)3]2), which exhibits an ESR spectrum consisting of a septet of decuplets (g = 2.00506, a(14N) = 5.26 G, a(7Li) = 0.69 G). The complexes [(THF)3Li3(mu 3-X)(Te(NtBu)3)] (4a, X = Cl; 4b, X = Br; 4c, X = I) are obtained from the reaction of [Li2Te(NtBu)3]2 with lithium halides in THF. The iodide complex, 4c, has a highly distorted, cubic structure comprised of the pyramidal [Te(NtBu)3]2- dianion which is linked through three [Li(THF)]+ cations to I- Crystal data: 4c, triclinic, space group P1, a = 12.611(8) A, b = 16.295(6) A, c = 10.180(3) A, alpha = 98.35(3) degrees, beta = 107.37(4) degrees, gamma = 108.26(4) degrees, V = 1829(2) A3, Z = 2. PMID- 11209614 TI - Molecular structures of carbonyl-linked bis(dioxolene) complexes: can a carbonyl group act as an effective ferromagnetic coupler? AB - Molecular structures of two bis(ZnIIdioxolene) complexes are described: (TpCum,MeZn)(2)1-H2 (C106H123.50B2N12O10Zn2), tetragonal, P4/ncc, a = 25.1810(2) A, b = 25.1810(2) A, c = 34.7744(2) A, alpha = 90 degrees, beta = 90 degrees, gamma = 90 degrees, Z = 8; (TpCum,MeZn)(2)1-H (C101H120B2N12O6Zn2), triclinic, P1, a = 13.6624(2) A, b = 13.80920(10) A, c = 26.62340(10) A, alpha = 96.6910(10) degrees, beta = 91.8560(10) degrees, gamma = 109.0190(10) degrees, Z = 2. One of the complexes, (TpCum,MeZn)(2)1-H2, has two protonated catecholate ligands, while the other complex, (TpCum,MeZn)(2)1-H, has one protonated catecholate and one semiquinone ligand. When reacted with PbO2, a labile S = 1, bis(ZnIIsemiquinone) complex is formed in which the two semiquinones are attached to a common carbonyl group. PMID- 11209616 TI - Square pyramidal dialkoxo-bound monooxo-vanadium(V) complex and its behavior in solution. PMID- 11209615 TI - Influence of the inner coordination sphere on the Ru(III)--cyanamido ligand-to metal charge transfer chromophore. PMID- 11209618 TI - Unexpected reactivity of Rh(TPP)I(CO) toward an alkoxide in CH2Cl2: synthesis and crystal structure of Rh(TPP)(CH2Cl). PMID- 11209617 TI - Fixing carbon dioxide with copper: crystal structure of [LCu(mu-C2O4)CuL][Ph4B]2 (L = N,N',N"-triallyl-1,4,7-triazacyclononane). PMID- 11209619 TI - Heteroleptic platinum(II) complexes with crown thioether and phosphine ligands. I: Crystal structures of [Pt(9S3)(dppm)](PF6)2 and [Pt(9S3)(PPh3)2](PF6)(2)X2CH3NO2. PMID- 11209620 TI - Facile and mild deboronation of o-carboranes using cesium fluoride. PMID- 11209621 TI - Synthesis and ion-binding studies of a platinum(II) terpyridine complex with crown ether pendant. X-ray crystal structure of [Pt(trpy)(S-benzo-15-crown-5)PF6. PMID- 11209622 TI - A neutral triangular supramolecule formed by Mo2(4+) units. PMID- 11209623 TI - Protonation of coordinated N2 on tungsten with H2 mediated by sulfido-bridged dinuclear molybdenum complexes. PMID- 11209624 TI - Conducting randomized, controlled trials. Experience with the dysfunctional uterine bleeding intervention trial. AB - OBJECTIVE: To conduct a randomized, controlled trial (RCT) to examine issues associated with therapeutic alternatives to standard hysterectomy for women with dysfunctional uterine bleeding. STUDY DESIGN: Participants were to be randomly assigned to one of three treatment groups: hysterectomy, endometrial ablation and medical management. Recruitment was targeted at 375 women. RESULTS: Despite multiple recruitment strategies, recruitment was weak, with only five women enrolled after six months. Providers and women screened for eligibility often expressed discomfort with randomization. The protocol was amended to an elective treatment cohort design with a randomization component. Recruitment improved, with 37 women enrolled after four months. CONCLUSION: The success of RCTs may be affected by multiple factors. Acceptance of the protocol by patients and providers is essential. The RCT may present providers with a conflict between the goals of research and of providing optimal individualized care. Thus, RCTs may not always be appropriate for studies designed to examine best treatments in clinical practice, and nonrandomized designs may provide appropriate alternatives in some cases. PMID- 11209625 TI - Preinduction cervical ripening techniques compared. AB - OBJECTIVE: To assess the clinical efficacy of pharmacologic, mechanical and combination techniques of cervical ripening. STUDY DESIGN: From March 1997 to August 1998, all cervical-ripening patients at Lehigh Valley Hospital were randomly assigned to three groups: intravaginal misoprostol, intracervical Foley catheter, or combination prostaglandin E2 (PGE2) gel and Foley catheter. Inclusion criteria included Bishop score < or = 5 and no contraindication to labor. The remaining delivery process was actively managed according to established guidelines. Multiple variables in perinatal outcome were analyzed, with the cesarean section rate and time from ripening to delivery as the main outcome variables. RESULTS: Of the 205 patients, 65 were randomized to the misoprostol group, 71 to the Foley group and 69 to the catheter-and-gel group. There were no differences between groups in delivery indications, maternal demographics, ultrasound findings, labor interventions, intrapartum times, mode of delivery, postpartum complications or neonatal outcomes. The misoprostol group demonstrated a higher rate of uterine tachysystole and required oxytocin less when compared to the two catheter groups. CONCLUSION: The higher rate of uterine tachysystole with misoprostol did not increase the cesarean section rate. The higher rate of oxytocin required by the two catheter groups did not increase the delivery time intervals. There appears to be no benefit to adding intracervical or intravaginal PGE2 gel to the intracervical Foley balloon. The misoprostol and catheter ripening techniques have similar safety and efficacy. PMID- 11209626 TI - Prenatal eradication of Hb Bart's hydrops fetalis. AB - OBJECTIVE: To evaluate the effectiveness of prenatal prevention of Hb Bart's hydrops fetalis. STUDY DESIGN: The study was a prospective descriptive analysis of pregnant women attending an antenatal clinic between June 1990 and June 1998. The study consisted of two periods, the first half with no prenatal diagnosis (PND) (1990-1994) and the second half with PND. During the study period, all cases of Hb Bart's hydrops fetalis were prospectively collected and postnatally confirmed. In the second period, prenatal strategy to control severe thalassemia was introduced. The strategy included (1) carrier identification by retrospective (history review for known risk) and prospective screening (simple erythrocyte osmotic fragility test) in women without known risks, (2) the couples at risk were offered genetic counseling and cordocentesis, (3) analysis of fetal blood for diagnosis, and (4) counseling for termination of pregnancy. RESULTS: During the first half of the study, the prevalence of Hb Bart's hydrops fetalis was 0.305 (89 in 29,399 deliveries). There were no fetuses with Hb Bart's hydrops fetalis among 16,360 screened pregnancies in the second half. However, of 6,856 pregnancies in the second half not screened due to a late first visit, 10 (0.15%) fetuses had Hb Bart's hydrops fetalis. Among the screened group, cordocentesis was performed in 361 pregnancies at risk, 170 and 191 from retrospective and prospective screening, respectively; and 75 (20.8%) were proven to have Hb Bart's disease, which was diagnosed before hydropic changes occurred. CONCLUSION: The strategy proved effective in preventing Hb Bart's hydrops fetalis, and extensive experience with it suggests that it be considered an effective way to control severe thalassemia. PMID- 11209627 TI - Gonadotropin-releasing hormone for infertility in women with primary hypothalamic amenorrhea. Toward a more-interventional approach. AB - OBJECTIVE: To assess the effectiveness of a protocol of pulsatile gonadotropin releasing-hormone (GnRH) in treating infertility in women with primary hypothalamic amenorrhea. STUDY DESIGN: Retrospective analysis of 44 cycles treated at an infertility center. Twenty-four patients with primary hypothalamic amenorrhea were treated intravenously with pulsatile GnRH using 5 micrograms per bolus every 90 minutes. Ultrasound monitoring and cervical assessment by Insler's scoring system allowed timed injection of human chorionic gonadotropin (hCG) and intrauterine insemination if needed. Luteal support was provided with hCG. RESULTS: The ovulation rate was 95% with the 5-microgram dose. A single follicle was produced in 91% of cycles. The overall pregnancy rate per ovulatory cycle was 45%, and the pregnancy rate per patient was 83%. In patients treated previously with exogenous gonadotropins, poor results were observed. Only one case of mild overstimulation was reported. CONCLUSION: Pulsatile GnRH is an effective and safe method of treating infertility in women with primary hypothalamic amenorrhea, thus simulating normal ovulation; however, more-interventional management, including the qualitative estrogenic response, may lead to optimal results and increase the pregnancy rate. PMID- 11209628 TI - Early diagnosis of ectopic pregnancy. Does use of a strict algorithm decrease the incidence of tubal rupture? AB - OBJECTIVE: To determine if tubal rupture rates are decreased when a strict diagnostic algorithm is employed in the evaluation of women with suspected ectopic pregnancy as compared to individualized diagnostic methods. STUDY DESIGN: Between 1994 and 1996, a group of investigators at Charleston Area Medical Center employed a strict diagnostic algorithm consisting of serum quantitative human chorionic gonadotropin (hCG) levels, progesterone levels, ultrasound and endometrial curettage in order to expedite diagnosis when ectopic pregnancy was suspected (group A patients). Other practitioners employed traditional criteria in similar clinical situations (group B patients). Medical records of patients diagnosed with ectopic pregnancy in this period were retrospectively reviewed. Demographic data, clinical and laboratory characteristics, and rate of tubal rupture were compared. RESULTS: Sixty-one of 122 patients were diagnosed with ectopic pregnancy by strict criteria. These patients did not differ significantly from those evaluated by an individualized approach in regard to age, gravidity, parity or risk factors for ectopic pregnancy. Menstrual age, hCG levels and progesterone levels were similar as well. Group A patients had a median diagnostic interval of 2 days, with a range of 0-16. Group B patients had a median diagnostic interval of 8 days, with a range of 0-44 (P < .001). Of patients evaluated by this strict algorithm, 3.3% experienced rupture as compared to 23% of patients in group B (P < .001). CONCLUSION: Use of a strict diagnostic algorithm in the evaluation of patients with suspected ectopic pregnancy resulted in decreased tubal rupture rates. Such an algorithm could be disseminated to all locations for triage of patients and use in a standardized manner. This practice could result in a reduction in loss of reproductive function and mortality secondary to ectopic pregnancy. PMID- 11209629 TI - Risks and adverse outcomes of sexually transmitted diseases. Patients' attitudes and beliefs. AB - OBJECTIVE: To determine women's awareness and level of understanding of the risks and sequelae of sexually transmitted diseases (STDs). STUDY DESIGN: The study was a cross-sectional survey of 103 women seen at an urban center. We recruited women from several clinical sites: (1) patients with signs or symptoms of an STD seen in a busy women's urgent care unit, (2) women enrolled in clinical studies for STDs or bacterial vaginosis, (3) patients admitted to the hospital and found to have an STD, and (4) women at high risk based on age and sexual activity. A trained female interviewer administered the survey to women agreeing to participate. The questionnaire assessed the patient's awareness of various STDs and their association with adverse outcomes. The survey also evaluated women's knowledge regarding STD prevention. Descriptive analyses were performed using SAS (Cary, North Carolina) on the 103 patients surveyed. RESULTS: The median age of our survey population was 23, 66% were nonwhite, and 37% were on public assistance or uninsured. The population was at high risk for STDs based on the reported history of infection with Neisseria gonorrhoeae and Chlamydia trachomatis (6% and 38%, respectively). Of the 103 women surveyed, 33% had never heard of pelvic inflammatory disease (PID), and 79.6% could not identify any adverse sequelae of PID. Sixty-five percent were unaware that PID increases the risk of ectopic pregnancy, and 56.3% were unaware that it could result in chronic pelvic pain. When asked if they knew of any methods to prevent or reduce their risk of STDs, only 18% mentioned barrier contraception (condoms). Over 57% of respondents could not name a way to prevent STDs. CONCLUSION: Increased educational efforts targeted at high-risk individuals are necessary to improve knowledge of STDs and their adverse sequelae. With greater knowledge and awareness, individuals and couples may be more likely to practice protective behaviors, such as reducing high-risk exposure, and to increase preventive measures, such as barrier contraception use. PMID- 11209630 TI - Early postpartum discharge at a university hospital. Outcome analysis. AB - OBJECTIVE: To determine whether implementation of an early hospital discharge policy was effective in safely reducing hospital stay and acceptable to patients. STUDY DESIGN: The study was a prospective, observational trial. Early discharge was defined as discharge from the hospital either on the first day after vaginal delivery or on the second day after delivery by cesarean section. A "stayover mom" policy was subsequently implemented to allow a mother the option to remain in the hospital overnight after discharge. This prospective study was divided into three consecutive three-month periods: (1) routine care (n = 576), (2) early discharge (n = 622), and (3) early discharge with stay-over mom (n = 574). Primary outcome measurements were length of hospital stay and patient willingness. RESULTS: With proper review of written instructions, all eligible patients were willing to be discharged early. As compared with the routine care group, the length of hospital stay was shorter by 0.8 days (95% CI, 0.4-1.2 days) in the early discharge group (P < .01) and by 1.1 days (95% CI, 0.5-1.7 days) in the early discharge with stayover mom group (P < .005). The stayover mom policy was more desirable because of limitations in obtaining timely transportation and concern about the infant warranting continued observation. The need for maternal readmission was rare (15 cases, 0.8% of total), with endometritis equally common (n = 3 in each group). CONCLUSION: Early postpartum discharge, especially including a stayover mom policy, was acceptable to our predominantly Medicaid population. The reduced hospital stay was not associated with increased maternal morbidity. PMID- 11209631 TI - Persistent postpartum urinary retention in contemporary obstetric practice. Definition, prevalence and clinical implications. AB - OBJECTIVE: To prospectively evaluate the prevalence, presumed etiologies and clinical implications of persistent postpartum urinary retention in modern obstetric practice. STUDY DESIGN: The study population comprised 8,402 consecutive, unselected parturients delivered in a university-affiliated maternity hospital over a one-year period. If a woman was unable to void spontaneously until the third postpartum day despite intermittent use of a Foley catheter, a diagnosis of persistent postpartum urinary retention was established. Patients were treated by insertion of a Foley catheter for up to two weeks and subsequently by a suprapubic catheter. Obstetric data were collected from the hospital records. RESULTS: Four patients (0.05% of the study population), aged 29 37 years, developed persistent postpartum urinary retention. Risk factors included vaginal delivery after cesarean section, prolonged second stage of labor, epidural analgesia, and delayed diagnosis and intervention. Urodynamic evaluation, performed on two patients one month after removal of the suprapubic catheter, revealed genuine stress incontinence in one and detrusor instability in another. None had had any lower urinary tract symptoms before pregnancy and delivery. CONCLUSION: Persistent postpartum urinary retention in contemporary obstetric practice is rare but may be associated with long-term bladder dysfunction. Early diagnosis and intervention are required to prevent irreversible bladder damage. PMID- 11209632 TI - Acute exacerbation of recurrent pelvic inflammatory disease. Laparoscopic findings in 141 women with a clinical diagnosis. AB - OBJECTIVE: To evaluate the accuracy of the clinical diagnosis of recurrent pelvic inflammatory disease (PID) and to determine the positive and negative predictive value of laboratory tests for the diagnosis of PID. STUDY DESIGN: According to a prospective study design, 141 consecutively hospitalized patients with the clinical diagnosis of PID were evaluated. The basic inclusion criterion was a history of at least one episode of PID. Standard laboratory tests were performed, specimens for aerobic and anaerobic culture and for Chlamydia trachomatis isolation were obtained, and temperature was regularly monitored. All patients underwent laparoscopy under general anesthesia within 24 hours of admission. RESULTS: The clinical diagnosis of PID was confirmed by laparoscopy in 30% of patients. In almost one-third of patients, at laparoscopy the pelvic organs were within normal limits. Adhesions without signs of PID were found in 16%. The third most-frequent finding was endometriosis (14%). Neither the individual monitored parameters nor their combination reached satisfactory positive and negative predictive values for diagnosing PID. CONCLUSION: Recurrent clinical symptoms and laboratory signs of PID should be an indication for confirming or excluding the clinical diagnosis by laparoscopy. PMID- 11209633 TI - Pregnancy rate and embryo loss in the NK1.1+ T cell-depleted mouse. AB - OBJECTIVE: To determine the role of natural killer cell (NK) 1.1+ T cells in pregnancy and in embryo loss. STUDY DESIGN: Four groups of C57 mice, consisting of 20 animals each, were studied. Groups A and B included pregnant females treated with anti-NK1.1 monoclonal antibodies until they gave birth or non-NK1.1 depleted antibodies, respectively. In order to evaluate the role of NK1.1+ T cells in pregnancy, female mice in group C were treated with anti-NK1.1 monoclonal antibodies every seven days starting seven days prior to mating until they gave birth. Control mice in group D were not NK1.1-depleted. NK1.1+ T cell depletion was determined by flow cytometric analysis. RESULTS: Depletion of NK1.1+ T cells did not significantly change the pregnancy rate, nor did it significantly alter the number of live births. Numbers of live births tended to decrease in NK1.1-depleted mice, with a mean number of live births of 4.66 as compared with 6.09 in NK1.1-depleted and nondepleted mice, respectively. Similarly, mice treated with anti-NK1.1 monoclonal antibodies every seven days starting seven days prior to mating became pregnant at a rate of 40% as compared with 60% in non-NK1.1-depleted controls. A comparable trend was observed in the number of live births, with a mean number of live births of 5.0 as compared with 6.1 in NK1.1-depleted and non-NK1.1-depleted mice, respectively. CONCLUSION: In the NK1.1-depleted mouse model, NK1.1+ T cells do not have any direct effect on pregnancy rate or on early embryo loss. PMID- 11209634 TI - High prevalence of high grade squamous intraepithelial lesions and microinvasive carcinoma in women with a cytologic diagnosis of low grade squamous intraepithelial lesions. AB - OBJECTIVE: To evaluate the histologic nature of low grade intraepithelial lesion (LSIL) in a region with a high prevalence of invasive cervical carcinoma and to propose a management protocol. STUDY DESIGN: Comparing the follow-up of 877 women with LSIL during a 43-month period, taking into consideration the histologic nature determined by colposcopic biopsy, endocervical curettage, conization or hysterectomy as the final pathologic diagnosis. RESULTS: During the study period, from July 1994 to February 1998, a total of 128,925 Pap smears were performed at our institute, with 877 (0.68%) diagnosed as LSIL. Among these, 722 women with CIN1-SIL and 32 with human papillomavirus-related changes (HPV-SIL) were enrolled in the study. Of the 543 women with CIN 1/squamous intraepithelial lesion, 145 (27%) cases of high grade squamous intraepithelial lesion were disclosed histologically, as were 16 (3%) cases of microinvasion. Among those followed at an interval of three months with a Pap smear alone, the persistence rate was 46.8%, while the regression rate was 40%. Thirty-two women with HPV/SIL underwent histologic evaluation, revealing 18% CIN 2/3 with no microinvasion. CONCLUSION: A high percentage of CIN 2/3 as well as microinvasive lesions will go unnoticed in the absence of colposcopic evaluation. PMID- 11209635 TI - Postpartum angiographic embolization for vulvovaginal hematoma. A report of two cases. AB - BACKGROUND: Puerperal hematomas can become a life-threatening obstetric emergency. Their incidence is 1 or 2/1,000 deliveries. When mainstay methods of suture and packing fail, arterial embolization becomes an excellent alternative to definitive treatment, laparotomy. CASES: A 32-year-old woman, para 2-0-2-2, developed extreme rectal and vulvar pain one hour postpartum. A 12 x 10-cm vulvovaginal hematoma was identified, drained, sutured and packed. Bleeding continued, blood products were administered, and selective angiographic embolization of the pudendal and inferior gluteal arteries was successfully performed. A 31-year-old woman, para 1-0-1-1, developed a left vaginal hematoma immediately postpartum. She failed vaginal packing and underwent angiographic arterial embolization successfully. The patient was discharged on the fourth postpartum day. At six weeks postpartum, neither patient had evidence of hematoma formation. CONCLUSION: In the setting of a puerperal hematoma refractory to conventional first-line therapy, arterial embolization provides a rational, effective alternative for achieving hemostasis with minimal morbidity. PMID- 11209636 TI - 10% hydroxyethyl starch for plasma expansion in the treatment of severe ovarian hyperstimulation syndrome. A case report. AB - BACKGROUND: Severe ovarian hyperstimulation syndrome is a complication of hormonal therapy for in vitro fertilization and carries the risk of renal failure. The injection of 6% hydroxyethyl starch has been used as a preventive measure. CASE: A 33-year-old woman was admitted with severe ovarian hyperstimulation syndrome after receiving gonadotropins as part of our in vitro fertilization protocol. Despite treatment with saline, albumin and abdominal taps, oliguria developed on the third day. The patient was transferred to the general intensive care unit and treated with 10% hydroxyethyl starch, furosemide and a further abdominal tap. Recovery was rapid. CONCLUSION: Ten percent hydroxyethyl starch is an efficient plasma expander. It is safe, biohazard free and cost-effective. It seems to effectively control severe ovarian hyperstimulation syndrome and to overcome acute prerenal failure. Larger prospective studies are necessary to further evaluate its role in the treatment of severe ovarian hyperstimulation syndrome. PMID- 11209637 TI - Contribution of diminished ovarian reserve to hypofertility associated with endometriosis. AB - OBJECTIVE: To determine if ovarian reserve, as measured by day 3 levels of E2 and FSH, was different in patients with endometriosis as compared to controls. STUDY DESIGN: Case-control study of 75 women with laparoscopically staged endometriosis and 75 age-matched controls undergoing in vitro fertilization/embryo transfer for male factor infertility. RESULTS: In women with stage III/IV endometriosis (revised American Fertility Society staging), day 3 E2 and FSH levels were significantly higher than control levels (51.9 pg/mL and 12.6 mIU/mL versus 34.7 pg/mL and 9.7 mIU/mL, P < .03). In contrast, women with stage I/II endometriosis did not differ significantly when compared to controls (36.8 pg/mL and 10.4 mIU/mL versus 34.0 pg/mL and 10.2 mIU/mL). The total group showed significantly higher E2 levels (41.8 pg/mL versus 34.1 pg/mL, P < .03), but no significant differences in FSH levels were observed. CONCLUSION: These data show that women with stage III/IV endometriosis have relatively diminished ovarian reserve, while this situation is not noted in women with stage I/II endometriosis. This observation is consistent with progressive loss of ovarian reserve in women with increasing stages of endometriosis independent of age. PMID- 11209638 TI - Treatment of cervical pregnancy with cerclage, curettage and balloon tamponade. A report of three cases. AB - BACKGROUND: Cervical pregnancy is a rare form of ectopic pregnancy, historically requiring hysterectomy to control life-threatening hemorrhage. However, with early diagnosis, conservative procedures can preserve the uterus and fertility. CASES: Three cases of cervical pregnancy were treated successfully with curettage. Two cases utilizing precurettage and postcurettage hemostatic techniques were treated with curettage alone. A third case, not employing precurettage hemostatic maneuvers, required uterine artery embolization to control bleeding and avoid hysterectomy. CONCLUSION: Curettage alone, when preceded by cervical infiltration with a vasoconstricting agent, placement of a cerclage suture high on the cervix and followed by cervical canal tamponade with a Foley catheter balloon, can successfully treat early cervical pregnancy. PMID- 11209639 TI - Colon cancer during pregnancy. A case report. AB - BACKGROUND: The reported incidence of cancer during pregnancy is between 0.07% and 0.1%. The incidence of colorectal carcinoma in pregnancy was 1 per 13,000 liveborn deliveries during 1981-1989. CASE: A 33-year-old woman, gravida 2, para 1, was admitted at 30 weeks' gestational age with a history of rectal bleeding and right upper quadrant pain. Abdominal ultrasound and magnetic resonance imaging revealed a mass located on the posterior part of the right liver and a fetus with vertex presentation. Primary cesarean section and a right hemicolectomy and wedge biopsy from the metastatic lesion on the right side of the liver at 34 weeks' gestation was performed. Histologic examination confirmed serosal and lymph node invasion of moderately differentiated mucous-secreting adenocarcinoma of the cecum and adenocarcinoma metastatic to the liver. The patient received systemic chemotherapy. CONCLUSION: Only 1 of 41 cases of colon cancer during pregnancy above the peritoneal reflection has been reported to be localized to the cecum. Our case is the second such one. Women with colorectal carcinoma during pregnancy usually have a poor prognosis, which may be attributable to younger age and delay in diagnosis since the initial symptoms often are presumed attributed to normal pregnancy, as in this case. PMID- 11209640 TI - A tale of two head and neck societies. PMID- 11209641 TI - Justice triumphs for surgeon prosecuted under "anti-dumping" law. PMID- 11209642 TI - Fraud and abuse: past, present, and future. PMID- 11209643 TI - Health plan accountability: state and federal initiatives. AB - Patients' rights legislation is high on the agenda of more than a few legislators this year, both nationally and at the state level. Although many proposals are being considered by state and federal lawmakers, one of the more significant legislative measures under debate would hold health plans legally accountable for medical treatment decisions they make, control, or influence. Of course, under the current professional liability system, only physicians and hospitals are legally responsible for the quality of patient care. Not surprisingly, then, the expansion of professional liability law to include managed care organizations (MCOs) is a contentious issue. PMID- 11209644 TI - Best healthcare facility. Venture House, Queens, NY. Thanhauser + Esterson Architects. PMID- 11209645 TI - Can it happen here? Panic over mad cow had already infected Europe. Now it's our turn. PMID- 11209646 TI - No fall insurance. PMID- 11209647 TI - Tapping and resolving consumer concerns about health care. PMID- 11209648 TI - A prescription for mental distress: the principles of psychosomatic medicine with the physical manifestation requirement in N.I.E.D. (Negligent Infliction of Emotional Distress) cases. PMID- 11209649 TI - The Americans with (or without) Disabilities Act: pre-employment medical inquiries and the non-disabled. PMID- 11209650 TI - Medical records and your privacy: developing federal legislation to protect patient privacy rights. PMID- 11209651 TI - Port-access surgery: pros and cons. PMID- 11209652 TI - Gene therapy for coronary artery disease. PMID- 11209653 TI - Optimal temperature for routine cardiopulmonary bypass. PMID- 11209654 TI - Pediatric interventional cardiology: the cardiologist's role and relationship with pediatric cardiothoracic surgery. AB - The advances in pediatric interventional cardiac catheterization have changed the therapeutic strategy for many patients with CHD. The procedure of choice for valvar stenosis, recoarctation, collateral vessel occlusion, and branch PA stenosis has moved from the operating room to the catheterization laboratory. Effective and safe transcatheter interventions now exist for closure of ASDs, VSDs, and PDAs and are considered viable alternatives to surgical closure. Other interventional catheterization procedures are currently being investigated to complement the surgical management of patients with complex anatomy, including covered stents for repair of aortic aneurysms, covered stents to complete the Fontan circulation in patients after a modified Glenn shunt, multiple stent designs for all vascular stenoses, percutaneous PA band, and transcatheter resurrection of the pulmonary valve in patients with severe pulmonary regurgitation. The rapid advances in the technology used in the catheterization laboratory will serve to improve the care we provide for our patients and extend the range of interventions performed outside of the operating room. Pediatric cardiologists and congenital heart surgeons must understand each other's interventional techniques and how they can be used in a coordinated fashion. This may involve staged therapy with transcatheter intervention before surgery, transcatheter interventions in the operating room, or modifications of surgical techniques to facilitate future interventional catheterization completion of a staged repair of complex disease. This interaction is essential for the optimal management of our patients with both straightforward lesions and complex anatomy. PMID- 11209655 TI - Turbine blood pumps. AB - After years of development and preclinical testing, clinical trials of the MicroMed DeBakey VAD began in November 1998 in Europe and in June 2000 in the United States. As of August 2000, 44 patients in Europe and 3 patients in the United States have undergone implantation with the MicroMed DeBakey VAD. In conclusion, data from the European clinical trial of the MicroMed DeBakey VAD support the safety and performance of the device. Results show that the device provides adequate left ventricular and circulatory support in patients with end stage heart failure without unduly jeopardizing patient safety. Moreover, the device provides advantages not inherent to commercially available pulsatile devices: (1) miniature size, enabling implantation in smaller patients; (2) ease of implantation; (3) reduced surgical bleeding; and (4) a low incidence of postoperative infections, often a limiting factor with other devices. The MicroMed DeBakey VAD European clinical trial is the first demonstration of the compatibility of continuous blood flow with adequate tissue perfusion and overall maintenance of life for up to 4.5 months. This initial experience with the MicroMed DeBakey VAD suggests that the pump can provide circulatory support to bridge patients to cardiac transplantation and may provide an improved quality of life for the patient with end-stage heart failure. PMID- 11209656 TI - Recent advances in reconstructive surgical management of hypoplastic left heart syndrome. PMID- 11209657 TI - Aortic surgery in the Marfan syndrome. PMID- 11209658 TI - Videoscopic mitral valve repair and replacement using the port-access technique. PMID- 11209659 TI - Single-stage complete unifocalization and repair for tetralogy of Fallot, pulmonary atresia, and major aortopulmonary collateral arteries. PMID- 11209660 TI - Winter mortality in relation to climate. AB - We report further details of the Eurowinter survey of cold related mortalities and protective measures against cold in seven regions of Europe, and review these with other evidence on the relationship of winter mortality to climate. Data for the oldest subject group studied, aged 65-74, showed that in this vulnerable group, high levels of protection against indoor and outdoor cold at given outdoor temperatures were found mainly in countries with cold winters, and were associated with low levels of excess mortality at a given level of outdoor cold. Regions such as London that had poor protection against cold and/or high baseline mortalities had higher levels of winter excess mortality than expected for the coldness of their winters. PMID- 11209661 TI - Cold climate and coronary mortality in Sweden. AB - In many European countries there is a tendency towards higher coronary mortality in the northern parts of the country. Furthermore the highest coronary mortality rates are found in the colder parts of Europe. We studied the regional variation in coronary mortality in the 284 Swedish municipalities during a ten-year period and the relation to the cold exposure in each municipality during the same time period. METHODS: Mortality rates for each municipality were acquired from the death certificates and indirectly standardised against the country. Temperature readings from measurements 5 times a day during daytime were used to form a cold index. We also compensated for wind chill by using Siples wind chill index. Multiple regression models were used. Second degree polynomials were used for the explanatory variables. RESULTS: There was a strong relation between the cold exposure in a municipality and coronary mortality. The cold index alone could explain 39% of the regional variation in coronary mortality. In a multiple regression model, cold index was the strongest explanatory variable. The coronary mortality in the coldest decile of the population was 40% higher than in the country as a whole. CONCLUSIONS: There is a strong regional association between cold exposure and coronary mortality in Sweden. However, in this type of study, it is not possible to determine whether this association is a causal one or not. PMID- 11209662 TI - Winter mortality in Emilia-Romagna, Italy. AB - In this epidemiological study we have studied during 1997 in Emilia-Romagna (population about four million) Italy, mortality from ischaemic heart disease, hypertension, cerebrovascular and respiratory disease in 50-89 year-olds. The data were collected from "Ufficio Risorse Informative" and "servizio Meteorologico" of the Emilia-Romagna region. The results show high indices of deaths in the elderly, the highest being those of the 80-89 year-olds, during the winter with a maximum in January. There were some differences between males and females with regard to cold-related mortality of the different diseases. Comparing mortality rates of persons living in the North (Piacenza) and in the South (Rimini) of Emilia-Romagna, a consistent lower mortality was found in the people of Rimini. These results confirm the close relationship between advanced age, cold and excess mortality in Emilia-Romagna. The results suggest that at least two factors may be involved in explaining excess winter mortality: the sympathetic system changes in the elderly and the effects of cold on some haemostatic factors. PMID- 11209663 TI - Seasonal patterns of morbidity and mortality in the elderly in Ireland. AB - Weather conditions have been shown to have a strong association with health Status. (1,2) In this study we examined the relationship between meteorological conditions (average daily temperature, humidity, precipitation, and wind strength) and the seasonal morbidity (emergency hospital admissions and drug prescribing) and mortality patterns in the elderly (over 65 years) over a four year period in Ireland. Temperature (summer/winter variation of 10 degrees C) had the strongest (inverse) association with total mortality (correlation coefficient of 0.895). Circulatory diseases showed the strongest seasonal trend in mortality and a weaker trend for admissions. For respiratory diseases, the morbidity and admission seasonal patterns were similar. Circulatory and respiratory drug prescribing showed no strong seasonal pattern. On examination of the excess winter mortality in four different regions, it was found that the smallest summer/winter temperature difference (9.96 degrees C) occurred in Cork and was associated with the highest percentage difference in total mortality. The highest temperature difference (10.80 degrees C) occurred in Monaghan and this area was associated with the lowest percentage difference in total mortality. PMID- 11209664 TI - Mortality from cardiovascular diseases and its relationship to air temperature during the winter months in Dublin and Oslo/Akershus. AB - In many countries increased winter mortality from cardiovascular diseases (CVD) has been documented. A causal relationship between change in air temperature and change in number of deaths has been suggested. There is also evidence for a delay between a fall in air temperature and death (lag effect). We have investigated these relationships using mortality data for CVD (ICD-9: 390-459) and daily air temperatures in selected winter months (December to March) from two densely populated areas in Norway and Ireland, Oslo/Akershus and Dublin. A specially designed computer programme was used to select data from specific days in the ten years period. The days selected depended on the temperature change chosen between two consecutive days. We examined 2 types of temperature change, a large change and little or no change. An analytical technique involving the use of Spearman's correlations coefficients was used to investigate delays in mortality following a particular change in temperature. For groups of selected days, an inverse relation between mortality and air temperature was found. For neither the Oslo/Akershus nor the Dublin data was it possible to see a sudden increase in mortality following a large, sudden decrease in temperature and no evidence for a delay between a change in temperature and a change in mortality rate was found. PMID- 11209665 TI - Seasonal variation of deaths in Finland--is it still diminishing? AB - The seasonal variation of deaths in Finland during the period 1961-1995, and its possible diminution over time was examined on a daily and monthly basis. The daily pattern of deaths over the year was asymmetric, with a very steep rise in December (peak on December 26), a slow rise in late winter and spring, a secondary rise in June (peak on June 24) and a trough in late August. The December peak was 26% higher than the August trough and showed no diminution over the period studied. The second peak in June was 12% higher than the annual minimum and was particularly pronounced in deaths from ischaemic heart disease and among people dying at ages 35 to 64 years. The winter excess in all natural mortality was estimated to be 7.4% of all annual deaths, and it showed some diminution over time, from 8.4% in 1961 to 6.3% in 1995, mainly because of the steeper decline in mortality in late winter in the 1980s and 1990s compared with the previous periods. PMID- 11209666 TI - Cold and ischaemic heart disease. AB - As part of a comprehensive program, including an exercise test, a long-term ECG recording, a psychic stress test, and administration of nitrogylcerin, 268 patients with an acute myocardial infarction (AMT) were submitted to a cold pressor test, holding the right hand in ice water for 10 minutes. Electrocardiogram (ECG), blood pressure (BP), and heart rate (HR) were determined before and at 2 minutes intervals during cold exposure. The patients were followed for one year for re AMI, no AMI, and death, sudden (SD) or not sudden (OSD). Patients with SD showed a significantly higher rise in diastolic BP than those with no AMI (0.001 < P < 0.01) or OSD (0.01 < P < 0.05). HR increased more in SD than in no AMI patients (0.001 < P < 0.01). Different physiological and metabolic reactions to cold exposure will be discussed. PMID- 11209667 TI - Cold and ischaemic heart disease in the elderly. PMID- 11209668 TI - Seasonal cold, excursional behaviour, clothing protection and physical activity in young and old subjects. AB - Previous reports indicate that everyday excursional exposures may play a part in increased winter mortality (Donaldson et al 1997) and that the avoidance of cold stress is associated with low indices of cold related mortality in Europe (Eurowinter Group 1997). However, few prospective data have been reported on excursional data and risk factors for arterial disease. In a field study carried out on 21 young (mean age 23.5) and 24 elderly healthy subjects (mean age 73.6) there were no significant differences between winter and summer in the number or duration of outside excursions. Never the less, elderly subjects had significantly more clothing insulation (clo), both indoors and outdoors in the winter than in the summer (p < or = 0.001) and this was also the case for young subjects. The urine temperature of the elderly in the winter was significantly lower (p < or = 0.01) than in the summer but this was not seen in the young. Elderly physical activity was significantly higher in the winter than in the summer (p < or = 0.05) but not for the young. Thus, elderly subjects showed no material change in excursional behaviour in the winter, even though clothing protection was arguably inadequate in view of lower body temperature, accompanied by increased physical activity. Blood pressure was significantly higher in the winter (p < or = 0.01) in the elderly, though the extent to which activity levels contributed to this contrast is uncertain from these data. PMID- 11209669 TI - Seasonal variation of risk factors for cardiovascular disease and diet in older adults. AB - We have already published much of our data on the seasonal variation of cardiovascular disease risk factors in a cohort of 65-74 year old men and women living in Cambridge, UK. In this paper we give a concise overview of our findings and include previously unpublished data relating to diet. Seasonal variation in intake of fat, copper, beta-carotene and vitamins A, C and E were all found with increased fat, beta-carotene and vitamin A intakes in autumn and winter while vitamin C and E intakes peaked in summer. Seasonal variation of vitamin C intake and serum ascorbate concentrations were particularly pronounced. We postulate that low vitamin C levels in winter could be associated raised plasma fibrinogen and plasminogen activator-1 (PAI-1) concentrations and therefore with increased cardiovascular risk. PMID- 11209670 TI - Dependence of cold-related coronary and respiratory symptoms on age and exposure to cold. AB - Cold causes cardiopulmonary stress often perceived as shortness of breath or chest pain, and causes exacerbation of these symptoms in persons suffering heart or lung disease. We investigated the prevalence of these symptoms and their association with sex, age and cold exposure in a population-based sample of 1,785 persons who lived in three areas of Finland. The exposure to cold was measured by the annual number cold days (mean daily temperature below 0 degree C) in the resident locality and weekly hours spent in the cold in winter. Shortness of breath was 25% and chest pain 52% more common in females than in males, and their prevalence increased by 24% and 77%, respectively, for every 10 years of age. The prevalence of shortness of breath increased by 5% and chest pain by 6% for every 10 cold days in the resident locality, and by 6% and 7% for every 10 hours spent in the cold, respectively. We suggest that environmental cold, measured by the number of cold days throughout the year and weekly hours spent in the cold, may provoke cardiopulmonary symptoms independent of sex and age. PMID- 11209671 TI - Physiological and haematological responses to cold exposure in the elderly. AB - Throughout Europe, including Norway, increased winter mortality from cardiovascular diseases (CVD) is well described. However, while there are associations between high CVD mortality and cold climate, the reason for the excess deaths is not entirely known. Recent epidemiological evidence suggests that brief outdoor exposure to cold conditions may be linked to increased winter mortality in the elderly. However, the question as to whether alterations in the haemostatic system following exposure to cold could be responsible for the increased winter risk has been little investigated in elderly subjects. In this study, we have compared the effect of exposing lightly clothed healthy elderly men and women (60-70 years) for 90 minutes to either a mild cold stress (16 degrees C) or thermoneutral conditions (28 degrees C). Measurements of a variety of autonomic and haematological parameters were made in order to compare to what extent exposure to cold stress affects production of thrombogenic risk factors. The overall autonomic responses clearly showed that the subjects were mildly cold exposed. The main changes in the blood system were a cold exposure increase in hemoconcentration and an increase in the fibrinolytic parameter, t-PA. This coupled with other changes support previous findings and it is concluded that short term mild cold exposure in the elderly initiates a mild inflammatory reaction and a tendency for an increased state of hypercoagulability. PMID- 11209672 TI - Atmospheric heat exchange of the human being, bioclimate assessments, mortality and thermal stress. AB - In epidemiological investigations of the impact of the atmospheric environment on mortality usually only air temperature, in addition to sometimes relative humidity, are used, although it is generally known that the heat exchange conditions of the human body also depend on water vapour pressure, wind velocity, and short- and long-wave radiation. The state-of-the-art approach to this problem is the application of complete heat budget models which allow thermophysiologically significant assessments of the above-mentioned meteorological variables taking metabolic rate and isolation of clothing into account. The application of such a model to 30-year mortality data of Baden Wurttemberg (SW-Germany) shows, in winter, increasing daily mortality rate with decreasing "perceived temperature." (a term which relates temperature to a fixed standard condition). A sudden warming during a cold period also results in an increase in mortality, a certain contradiction which has not yet been able to be explained. During cold spells a marked increase in mortality with a delay of 3 days can be observed. Above normal values last for about 4 weeks and will then be partially compensated by an "undershot". Generally the explanation of variance in winter is distinctly lower than in summer, probably because in winter there is rarely direct exposure to outdoor conditions. The degree of cold stress is likely to serve only as an indicator for indoor conditions which promote infectious diseases. PMID- 11209673 TI - Indoor climate and health. PMID- 11209674 TI - Thermal factors--indoor climate. AB - From 1950 and until today, building technology has developed continuously, especially concerning insulation and sealing (2). Therefore the Norwegian houses of today resist cold and wind very well. But there are still factors that can provide thermal discomfort. Some of these factors can for instance be open indoor solutions, placement and number of windows and sources of heat, upgrading and maintenance of old houses. Important thermal parameters are draught and air velocity, vertical air temperature differences, asymmetry of thermal radiation, floor temperature and relative humidity (4). PMID- 11209675 TI - Living in a Norwegian house. PMID- 11209676 TI - Thermal and relative humidity conditions in the houses of the aged living in Ireland, and their risk of effective acute cold stress. PMID- 11209677 TI - Accidental hypothermia in the elderly. AB - Accidental hypothermia is known to be a hazard to elderly people in temperate and cold climate. This is a review of the literature focusing on risk factors, clinical presentation and treatment of hypothermia in the elderly. The most important risk factors are connected to ageing itself and to the morbidity often found in elderly hypothermia victims. Knowledge about treatment of severe accidental hypothermia in elderly people is based on experience from few cases and some minor prospective studies mainly on rewarming of younger patients. Clinical treatment protocols seems to be based on experience from younger patients. Based on general knowledge in geriatric medicine and experience from three recent cases of hypothermia in the elderly, the use of careful, active external rewarming and a low stress strategy are recommended for elderly patients. PMID- 11209678 TI - Rewarming from hypothermia. Newer aspects on the pathophysiology of rewarming shock. AB - The fatal circulatory derangements often observed when resuscitating victims of accidental hypothermia by rewarming are recognized as a falling cardiac output and a sudden drop in blood pressure, termed "rewarming shock". The real cause of this rewarming shock, or rewarming collapse, is, so far, unknown. This review presents current information exploring different aspects of the compromised circulatory function during hypothermia and especially after rewarming and supports the hypothesis that posthypothermic circulatory instability may be caused by cardiac insufficiency and alteration of the peripheral vascular bed. Cellular calcium overload, disturbed calcium homeostasis, changes in myocardial myofilament responsiveness to intracellular calcium as well as impaired high energy phosphate homeostasis could all be proposed as important factors leading to the changes observed in the hypothermic heart. Together with alteration of capillary function, increased capillary leakage of plasma protein, changes in intra- and extravascular volume-homeostasis and alteration of autonomous vascular control they all contribute to a maintained low cardiac output during and after rewarming which is associated with a fatal outcome. PMID- 11209679 TI - Strategies for prevention of cold stress in the elderly. AB - Human health and wellbeing require simple and effective strategies for prevention and alleviation of harmful effects of cold exposure. Adoption of a strategy should consider the type of cold stress; (1) whole body cooling, (2) extremity cooling, (3) convective cooling (wind chill), (4) conductive cooling (contact), and (5) airway cooling. The prime goal is to prevent tissue cooling. The risk, nature and magnitude of strain depend largely on the cooling effect, which results from the interaction of climate factors (mainly air temperature and wind), protection (clothing) and metabolic heat production (activity, "behaviour"). The effects (strain) of tissue cooling are acute, progressive or chronic. Acute effects are primarily thermoregulatory reflexes mediated by the sympathetic system and comprise immediate cardiovascular and respiratory reactions. Progressive effects are characterized by gradual temperature drop in peripheral or core tissues. This results in pain, neuro-muscular insufficiency, sensory loss and, eventually, cold injury. Chronic effects are likely to affect peripheral nerves and vessels, as well as cardio-respiratory function. The progressive degradation of physiological functions in the elderly increases the risk of harmful effects with cold exposure. This requires careful examination of relevant assessment criteria, as well as the development of simple and efficient strategies for prevention of cold stress. PMID- 11209680 TI - Are cold exposure and reduction of growth hormone secretion in the elderly synergetic risk factors in cardiovascular diseases? PMID- 11209681 TI - Seasonal relationship between date of birth and date of death in Finnish centenarians. PMID- 11209682 TI - [Expression of single-chain Fv antibody for anti-beet necrotic yellow vein virus in Escherichia coli]. AB - The heavy chains variable region gene (VH) of monoclonal antibody against beet necrotic yellow vein virus (BNYVV) was amplified from total DNA extracted from anti-BNYVV hybridoma cells by PCR. Sequencing showed that the VH belongs to mouse subgroup II(A) and contains 360 bp, which code one hundred and twenty amino acids. The VH and VL genes were inserted into a plasmid which contains a linker sequence for constructing scFv gene. The new vector named pTC scFv. The scFv was produced in Escherichia coli and appeared binding activity with BNYVV antigen by ELISA method. PMID- 11209683 TI - Development of PCR-based markers linked to the fertility restorer gene for the polima cytoplasmic male sterility in rapeseed (Brassica napus L.). AB - Bulked segregant analysis was used to identify RAPD markers linked to the Rfp of pol cms in rapeseed (Brassica napus L.) from the fertile and sterile DNA bulks. DNA bands amplified from 1040 random 10-mer primers were screened. Two polymorphic bands S1019(720) and S1036(810) were found linked to the Rfp locus at the same side with a map distance of 5.8 cM and 12.3 cM respectively. These polymorphic fragments were cloned and sequenced. Nucleotide sequence information was used to design 20-24-mer oligo nucleotide primers for PCR amplification. The SCAR markers that generated from the long primers showed the same pattern of segregation as the original RAPD markers in the backcross population. The SCAR markers would facilitate selection on the Pol CMS restorer lines in rapeseed. PMID- 11209684 TI - [Construction and analysis of soybean genetic map]. AB - Molecular linkage maps provide a powerful tool for the analysis of plant genome structure and function including the detection of quantitative trait loci (QTL). The molecular linkage map of soybean was constructed using an 88-individual RIL population derived from a cross between cultivated Changnong 4 and semi-wild Xinmin 6. The map contains 22 linkage groups and 240 markers, including 100 RFLP, 33 SSR, 62 RAPD, 42 AFLP, 1 SCAR and 2 morphological markers. It covers approximately 3,713.5 cM of soybean genome. Analysis of 72 RFLP markers showed that 16 of them revealed two or more independent loci and it suggested that there is an extensive homologous region in soybean genome. This map compared very well with the other published soybean maps. PMID- 11209685 TI - [Analysis of 16S rDNA sequence and DNA-DNA hybridization of rhizobia isolated from Indigofera sp]. AB - Based on the previous studies on numerical taxonomy and SDS-PAGE of whole-cell protein, the rhizobia strains isolated from Indigofera sp. in loess plateau area of North-west China constituted a new cluster, the 16S rDNA sequence of representative strain SHL042 was tested, and the phylogenetic tree was produced. In this tree, the strain SHL042, R. tropici A, R. tropici B, R. leguminosarum, R. etli, R. hananesis, R. mongolense and R. gallicum constituted a branch of phylogenetic. Within this branch, the similarity values of 16S rDNA sequences were 95.4%, 95.5%, 96.3%, 95.8%, 96.3%, 97.9% and 97.7% respectively. The values were more than 95%. This indicated that these species should belong to the same genus. The values of DNA homology in the new cluster were all more than 80%, but the values between SHL042 and the strains of these species were less than 50%. Thus, the strain SH714 represented a new rhizobia species. PMID- 11209686 TI - [Expression of 3'-truncated preS/S gene in transgenic mice]. AB - The 3'-truncated preS/S region from HBV genome, encoding a transcriptional transactivator, was cloned and a recombination expression vector for 3'-truncated HBV preS/S sequences under the control of the CMV promoter was constructed by recombination DNA techniques. Then, the expression vector DNA was microinjected into pronuclei of fertilized mouse oocytes. Founders of transgenic mice harbouring the recombination gene which can be expressed were screened by polymerase chain reaction (PCR) at genomic DNA level and confirmed by ELISA andlysis at protein level. Two of 15 mice in one series of microinjections showed the expression of 3'-truncated preS/S gene from HBV genome. The expression vector of 3'-truncated preS/S gene might be helpful for further studies of relationship between the expression production of 3'-truncated preS/S sequence and HBV associated oncogenesis in vitro. The transgenic mice with expressing 3'-truncated preS/S gene will provide new insight into its roles in the development of human hepatocelluar carcinoma (HCC) in vivo. PMID- 11209687 TI - [Genetic analysis of sow productivity traits]. AB - Genetic analysis was conducted on the data of 3 populations with 1686 litters including Erhualian pigs, Large White and first cross. The phenotypic and genetic parameters among litter weight at birth (LW), average piglet weight at birth (APW), litter weight at 20 days (LW20), average piglet weight at 20 days (APW20), litter weight at 45 days (LW45), average piglet weight at 45 days (APW45) were estimated by sire model. The results indicated that Erhualian pigs had stronger maternal ability and slower growth rate compared to Large White. The first four traits (LW, APW, LW20, APW20) had larger maternal effects, while LW45 and APW45 had smaller maternal effects. The heritabilities of LW, APW, LW20, APW20, LW45, APW45 were 0.251, 0.277, 0.341, 0.330, 0.235, 0.186, respectively. The results indicated that direct selection was effective. According to our results, we considered that it was fit to select two traits (LW, LW20) out of these six traits to reflect sow productivity. Litter weight at birth could reflect the prolificacy of sow, litter weight at 20 days could reflect the maternal ability of sow. PMID- 11209688 TI - [The research on the expression of rabbit defensin (NP-1) gene in transgenic tomato]. AB - Rabbit defensin NP-1 is one kind of alpha-defensins. It is composed of 33 amino acids. It was firstly extracted from polymorphonnuclear neutrophile of rabbits. It displayed resistance to bacteria, fungi and virus, especially high resistance to bacteria. In our experiments NP-1 gene was constructed into a plant expression vector. Eight transgenic plants containing the rabbit defensin gene (NP-1) were obtained through agrobacterium-mediated transformation. The transgenic plants were analysized by PCR, Southern hybridization, Northern dot blot hybridization and in vitro microbicidical activity against E. coli and Fusarium oxysporum. The results showed that NP-1 gene was transformed into the tomato, and the transgene displayed physiological-level expression. The transgenic tomato also showed resistance to pathogen Fusarium oxysporum in vivo. Our experiments paved a way for pathogen resistance breeding of tomato. PMID- 11209689 TI - [Induction of polyploid in the Pacific abalone by caffeine-heat shock treatments]. AB - Polyploid of Pacific abalone, Haliotis discus hannai Ino, was induced by blocking Polar body I with caffeine-heat shock treatments. Fertilized eggs were treated with caffeine concentrations at: 2.5 mmol/L, 5 mmol/L and 10 mmol/L; heat shock temperatures at 24 degrees C, 26 degrees C, 28 degrees C, lasting for 10 min to 30 min, total 5 periods of time, beginning at 10 min post-fertilization. Both fertilizing and incubating at 21 degrees C sea water. The results of studies showed that the effective procedure for inducing triploid appeared to be 5 mmol/L and 10 mmol/L Caffeine concentration, heat shock temperature 26 degrees C, duration 10 min to 15 min, all beginning at 10 min after insemination. The percentage of triploid was 64.6%-77.8%, Comprehensive efficiency index of polyploid induction was 0.57-0.61. Under the condition of 5 mmol/L caffeine concentration and the temperature 26 degrees C for 30 min duration at 10 min post fertilization, 2.8%-3.6% tetraploid embryos could be produced. PMID- 11209691 TI - [Mutagenic analysis on the polyhedrin gene (polh) of Bombyx mori nuclear polyhedrosis virus (BmNPV)]. AB - In our early studies, the abnormal shape of the polyhedra of Bombyx mori nuclear polyhedrosis virus (BmNPV) induced by chemical mutagens of MMC. 9-AA and EMS occurred, and the genome of the mutated BmNPV obtained from the successive test had some change in the restriction endonuclease partners of EcoRI, BglII and BamHI. The present studies showed that the arrangement of the crystal lattice of the polyhedrin was disorderly, and the SDS-PAGE electropherogram of the polyhedrin depicted distinct change in comparison with control group. The results of sequencing analysis showed that many point mutations with characteristics of the base substitution had occurred at some sites of the BmNPV polh gene in three mutated groups, and these results funther revealed molecular mutagenesis of the mutagens effective to BmNPV. It was not confirmable that the point mutations of polh gene in the mutated BmNPV have relationship to abnormal shape of the polyhedra. PMID- 11209690 TI - [Induction of protective immune responses in rhesus monkey by immunization with recombinant plasmids of polyvalent epitopes of Plasmodium falciparum using cholera toxin B as adjuvant]. AB - The immunogenicity and protective efficacy of the DNA vaccine which include cholera toxin B subunit (CTB) and polyvalent protective epitopes of Plasmodium falciparum (awte gene) was assessed using rhesus monkeys as animal models. Recombinant plasmids of pCMV-CTB-AWTE were given to five rhesus monkeys three times with two weeks intervals by intramuscle (i.m.) route, immunization dose was 500 micrograms per plasmid per animal. High levels of anti-CTB and anti-malaria epitopes antibodies and P. falciparum epitope specific CTL activity were elicited. The vaccinated groups was challenged with 1.25 x 10(8) of P. cynomolgi parasites. All monkeys of the control group was patent for at least 34 days, the DNA vaccinated groups wasn't infected during the 60 days we detected. The cocktail DNA vaccine which contains multi-stage and multi-epitope antigen gene shows excellent immunogenicity and protective efficacy, the results also suggests that DNA vaccine plays an important role against malaria infection. PMID- 11209692 TI - [Establishment of a method for GUS gene transferring into wheat (Triticum astivum L.) embryos by low energy ion beam implantation]. AB - Physical parameters influencing transformation of wheat mediated by low energy ion beam, including type of ion, parameters of ion energy, dose and dose rate, were studied. Ar+ was regarded as suitable ions implanted in transformation. 20 25 keV of energy, 4.68 x 10(16) ions/cm2 of dose, 2.6 x 10(15) ions/cm2 of dose rate were chosen as appropriate implantation parameters. The suitable culture conditions for induction and growth of callus and the optimal selection scheme were established, After implantation and selection, resistant calli and hygromycin-resistant plantlets were obtained from three varieties. Molecular analysis data proved that GUS gene had integrated into the wheat genome. The mature embryo transformation efficiency of wherat variety Yangmai 5, Yangmai 158, Wanmai 32 reached 9.5%, 10.8%, 11.2% measured in produced hygromycin-resistant callus and 1.4%, 3.4%, 1.7% measured in regenerated plants, respectively, This experiment provides a basis for further investigation of wheat transformation system. Low energy ion beam mediated transformation can be extended to other plant recalcitrant to Agrobacterium tumefaciens as soon as methodological parameters are optimized. PMID- 11209693 TI - [Production of herbicide-resistant rice with transforming heterogene]. AB - Using pAHC20 (containing Bar gene), pWRG1515 (containing GUS gene and hygromycin phosphotransferase gene), and pCAMBIA3300 RG with Bar gene and snowdrop lectin (GNA) gene as donor DNA, the micro-adventitious shoots and the calli induced from mature embryos of Oryza sativa 87203, Eyi105, Shangnong aromatic glutinous rice as recipients were transformed with particle bombardment and Agrobacterium tumefaciens strain LBA4404 containing pAL4404, respectively. After chosen with phosphinothricin and antibiotic, GUS detection and PCR analysis, The results showed that the foreign genes had been transformed microprojectile-mediated to Oryza sativa Eyi105, the regeneration plants were obtained, and, 5 transgenic calli of Oryza sativa Eyi105 were obtained with Agrobacterium-mediated transformation. PMID- 11209694 TI - [A study of genetic character of cultivar Shiyuan 321 from G. barbadense x G. thurberi x G. hirsutum using isozyme and RAPD techniques]. AB - To study the genetic character of trispecific hybrid cultivar Shiyuan 321, we analyzed this cultivar and its parents by isozyme and RAPD techniques. The main results are as follows: (1) Esterase isozyme analysis showed that there was one specific band among cultivar Suiyuan 321 and its parents, G. thurberi and G. barbadense; (2) Six specific DNA fragments amplified by 4 primers were found among cultivar Shiyuan 321 and its parents G. barbadense, G. thurberi; (3) By comparing RAPD differences among Shiyuan 321 and its parents, it is indicated that the genetic heterogeneity of cultivar Shiyuan 321 is very high at its genomic DNA level. The above results proved that Shiyuan 321 is a trispecific cultivar from G. barbadense x G. thurberi x G. hirsutum as well as a new germplasm. PMID- 11209696 TI - [Detection of differentially expressed genes in hepatocellular carcinoma using DNA microarray]. AB - Large scale gene expression profiles between normal hepatocytes and hepatocellular carcinomas are detected with high throughput microarray. DNA microarrays were made by spotting PCR products of 4,096 human cDNAs onto a specially treated glass slides. The probes were prepared by labelling normal tissue mRNA and cancer tissue mRNA with Cy3-dUTP and Cy5-dUTP separately through reverse transcription. The arrays were then hybridized against the cDNA probe mixture and the fluorescent signals were scanned. The obtained data were analyzed from 4 repeated experiments. There are 903 genes of which the average ratios between Cy3 signal and Cy5 signal are greater than 3.0. These genes identified through this approach are potential candidates for hepatocellular carcinoma diagnosis and therapy. PMID- 11209697 TI - [Affect of heredity, disease and environment on the life-span of personage in History Book of Song Dynasty]. AB - The data have been sorted and calculated by statistics for personages' life-span according to surname and Yin-Yang type and disease according to the cause of pattern over 793 personage from the biography of emperor families' and official in feudal times and subjects of the feudal ruler in History Book of Song Dynasty. (1) For there are some genetic diseases causing their earlier death in surname Zhao's, the average value of life-span is shorter than the other surname of Wang, Li, Zhang, Liu and Chen's. Because the average value among those five surnames are not different each other, the character of the distribution of every one's tally with neuter alleles. (2) The average value in a population on a type of mild Yin and Yang is higher than the type of Yang only, P < 0.05. (3) Disease and bad environment are the limiting factors for life. Besides, to rise the resistance ability is an important path way for increasing our life-span. The attribute of a genetic system in Yin or Yang is an objective existence. Influence on life by genetics may vary with various disease and environment, but different disease is controlled genetically. A bad environment may affect life, but neuter environment would be affected the life through attribute of a genetic system in Yin or Yang type indirectly. PMID- 11209695 TI - [STR polymorphisms in five Chinese ethnic groups(2)]. AB - Population genetic studies were performed in Chinese Han, Hui, Mongolian, Tibetan and Uygur. Allele frequency distributions were analyzed for ten loci, i.e., D3S1358, VWA, CSF1PO, FGA, THO1, TPOX, D5S818, D13S317 and D7S820 by GeneScan. The results showed that there were 60 STR alleles and 149 genotypes in Han; 63 STR alleles and 144 genotypes in Hui; 69 STR alleles and 173 genotypes in Mongolian; 77 STR alleles and 168 genotypes in Tibetan; 70 STR alleles and 148 genotypes in Uygur. Significant differences were identified among ethnic groups (African-American, US-Caucasian and Chinese-Oriental), but similarity was found among the five Chinese populations, and immunogenomics and pharmacogenomics studied in this report. These findings indicated that the nine STR loci and amelogenin locus were very useful for individual identification in forensic science. PMID- 11209698 TI - [Studies of the origin of malignant rhabdoid tumor(MRT)--experimental researches on the MRT evolving in nude mice inoculated with violently variable HeLa cells]. AB - Under the prerequisite that the incidence of cancer or tumor in negatively controlled nude mice inoculated subcutaneously with feline or canine kidney cell cultures purified in vitro at passage 3 or higher (the modal chromosome number of FKC on passage 3 was 38 of diploid at the rate of 80%) was 0%(0/22) and 0%(0/10) respectively, and the incidence of progressively negative growing tumor in controlled nude mice inoculated subcutaneously with repeatedly-frozen- and thawed HeLa cell cultures of X strain was 20%(1/5), the negative growing malignant tumor (MT) was found in half of the nude mice inoculated subcutaneously with HeLa cell cultures of H strain(with modal chromosome number of 78 +/- 2 of sub-tetraploid at the rate of 40%), the progressively-growing malignant tumor was found in all the other 40 nude mice inoculated subcutaneously with HeLa cell cultures of other strains, with the incidence of MT in nude mice with KB strain (with modal chromosome number of 60 +/- 3 of hyperdiploid at the rate of 72%-76%) 10/10, the incidence of poorly-differentiated MT originated from epithelia in nude mice with X strain (with modal chromosomal number of 62 +/- 3 of hyperdiploid at the rate of 69%) 25/25, and the incidence of MRT in nude mice with in vitro cultured tumor cell NM20/X strain (with modal chromosome number of 68 +/- 3 of both hyperdiploid and subtetraploid at the rate of 52%) 5/5. After being continuously cultivated for 20 passages in vitro, HeLa cell of X strain was subcutaneously inoculated into nude mice and cultivated for 1 passage in vivo within 15 days, and then the developed growing MT was collected as HeLa cell of NM20/X strain on passage 0 and continuously cultivated for 11 passages to prepare for transplanting into nude mice again. Therefore, the highly variable strain of HeLa cells can be successfully selected by alternate cultivation in vitro and in vivo. Occasionally in another experiment, the progressively-growing MRT was found in all the 4 nude mice of one test group inoculated subcutaneously with 0.17 ml cell-cultures of super-high density containing 12.75 x 10(7) HeLa cells of KB strain on passages 10-11(with the rate of chromosome aberration high to 20% on passages 10-11 including 18% dicentric chromosome and 2% breakage chromosome). Although the incidence of MRT in nude mice inoculated subcutaneously with violently variable HeLa cells of NM20/X strain on passage 11, HeLa cells of KB strain on passages 10 11 reaches 100%(5/5) & 100%(4/4) respectively, yet it is requested that the inoculated live cell number is huge (5-12 x 10(7) cells per nude mouse), the tumor emerges immediately, develops violently, grows very fast, and has an extremely aggressive malignancy, the tumor is rich in the blood vessel giving a full supply of blood for it, and the mean value of major diameter X minor diameter of the tumor is essentially up to the standard of 30 mm x 20 mm in 16-22 days after the inoculation of the cells into the nude mice. The first finding of MRT in model animals provides an opportunity for answering the origin problem of MRT. Based on this reason, human uterus vertical epithelium may be an original tissue of MRT, thus opening up a new era for the research of MRT origin. It is also concluded as follows: 1. Cellular tumorigenicity is different among differently-karyotypic cells. 2. Highly variable strain of tumor cell line can be selected quickly and successfully in nude mouse. 3. Cellular tumorigenicity may be increased if chromosome aberration is very high. 4. The genetic characteristics of chromosomes of HeLa cells determines their tumorigenicity, chromosome number variation of HeLa cells has positive relationship with their carcinogenesis or tumorigenicity, and the turn of HeLa cells concerning their tumorigenicity from weak to strong is KB, X and NM20/X strains (excluding H strain, in which tumorigenicity remains to be determined by further experiments) respectively. PMID- 11209699 TI - Identification of RAPD markers tightly linked to wheat powdery mildew resistance gene Pm6.l. AB - Pm6 transferred from Triticum timopheevii L. to common wheat, is an effective resistance gene to powdery mildew disease caused by Erysiphe graminis f. sp. tritici. The RAPD technique, employing a total of 700 decamer primers, was used to identify polymorphic markers between resistant (IGVI463) and susceptible (Prins) near-isogenic lines. Primer OPV20 produced a 2,000 base pair (bp) reproducible fragment only in the resistant near-isogenic line. The 2,000-bp DNA fragment was present in all other introgression lines containing Pm6. Using the F2 mapping population from a cross of IGVI-463 (PI170914/7*Prins) x Prins, Pm6 was shown to be closely linked to the marker OPV20-2000 at a genetic distance of 3.0 +/- 2.2 cM. The marker was successfully used in detecting the presence of Pm6 in different genetic backgrounds. PMID- 11209700 TI - [Identification of the barley chromosome in wheat by GISH and RFLP]. AB - The barley chromosome in wheat was identified by genomic in situ hybridization (GISH) in which biotin labelled total genomic DNA of barley Betzes was used as probe and the unlabelled total DNA of common wheat Chinese Spring (CS) as blocking DNA. A series of wheat materials were tested as follows: two disomic alien substitution and monosomic alien addition lines, 2n = 43; two monosomic alien substitution lines, 2n = 42; seven disomic alien substitution lines, 2n = 42. RFLP probe psr131 on the short arm of the homologous group 2 was used to analyze the barley chromosome in wheat. The result indicated that there was a same band in barley Betzes and substitution line A5. The chromosome 2A of A5 was substituted by the chromosome 2H of barley. These materials will be useful in transferring the valuable genes in the chromosome 2H to wheat. PMID- 11209701 TI - [Genetic diversity of Fagoyrum tataricum cultivated in north Liangshan Prefecture of Yi Nationality, Sichuan, China]. AB - In the present paper is stated the accomplishment of the studies of 17 populations of cultivated Fagopyrum tataricum (L.) Gaertn. from the counties of Yuexi and Ganluo in North Liangshan Autonomous Prefecture of Yi Nationality, Sichuan Province, China by means of starch gel electrophoresis and cluster analysis of agrobiology features. Seven enzymes, and 15 loci were assessed. The result shows that the genetic diversity of F. tataricum within population is higher than in the South Prefecture and in species F. esculentum from other areas. The A, P, Ho and He are 1.9, 52.1%, 0.190 and 0.262 respectively. The FST is 0.199 which is close to the average level of wild plants. A conservation strategy of the genetic resource of F. tataricum is suggested. Two populations of local variety "Youchiqiao" have the richest genetic diversity, P = 60.0%, Ho = 0.260 and 0.301 and they should be protected particularly. Two populations of local variety "Xiaomiqiao" with higher genetic diversity, as well as three populations of local varieties of "Qiukuqiao", "Equkuqiao" and "Geluokuqiao" with special genetic position should be protected too. PMID- 11209702 TI - [Analysis of isozyme and RAPD for the germplasm lines from G. hirsutum x G. bickii]. AB - To study the effectiveness of Gossypium interspecific hybrid breeding on molecular level, the six germplasm lines from interspecific hybrids between G. hirsutum and G. bickii were analysed by the techniques of RAPD and isozyme electrophoresis. The main results were summarized as follows: (1) The basic zymograms of peroxidase isozyme of the six germplasm lines were similar to their G. hirsutum parent, but two out of the germplasm lines showed one specific band of the wild parent of G. bickii (pI 4.85); (2) The RAPD fingerprint showed distinct difference of genomic DNA among the germplasm lines; (3) The four specific DNA fragments of G. bickii were observed in RAPD patters of four out of the six germplasm lines. PMID- 11209703 TI - [Studies of the active site, thermostability and thermophilicity of the thermostable alkaline phosphatase by site-directed mutagenesis]. AB - Through PCR-mediated mutagenesis, three mutants E68S, S70A and E68SS70A around active site S(69) were obtained. Their enzymatic characteristics was determined. It was found that the specific activity of E68S ascended 8 times while its optional reactive temperature climbed 20 degrees C and its Tm descended 3 degrees C; the specific activity of S70A ascended 1 time while its optional reactive temperature climbed 5 degrees C and its Tm descended 2 degrees C; the specific activity of E68SS70A descended 50% while its optional reactive temperature climbed 5 degrees C and its Tm descended 19 degrees C. These result implied that the amino acids, beside the active site, were contributed not only to enzymatic activity but also to its thermostability and thermophilicity. The work provided the direction for mutation to improve enzymatic specific activity and studying the mechanism of thermostability and thermophilicity. PMID- 11209704 TI - [Differentiation genes are involved in homologous recombination in Streptomyces coelicolor]. AB - In S. coelicolor, the rapid increase of SCP2* plasmid conjugation efficiency and that of plasmid homologous recombination efficiency associates with development of aerial mycelium. Results of test of SCP2* plasmid conjugation and plasmid homologous recombination in one bld mutant and in three whi mutants show that while whiA mutant causes unstable plasmid conjugation efficiency, the other three mutants show no influence on plasmid conjugation, plasmid homologous recombination efficiency drops however more than 10 times in the four mutants. PMID- 11209705 TI - [Painting the chromosomes of fishes with human sex chromosome-specific DNA probes]. AB - Chromosome painting is one of the effective methods in studying the evolution of genomes. The chromosomes of the species of fishes--M. aculeatus, M. albus and D. rerio were painted respectively with human X and Y chromosome-specific DNA probes. The results showed that some homologous segments of human X chromosome were found in the genomes of all the three kind of fishes, all the segments were scattered on several pairs of homologous chromosomes in each kind of fish. But no homologous segment of the human Y chromosome was found. PMID- 11209706 TI - [Isolation and characterization of the porcine glial fibrillary acidic protein (GFAP) gene by CATS]. AB - Primers for the glial fibrillary acidic protein (GFAP) gene were designed from a human cDNA sequence aligned with the mouse GFAP gene on the principle of comparative anchor tagged sequence (CATS). The 412 bp PCR product isolated from Chinese Erhualian pig genome was characterized as the porcine GFAP gene by comparing the sequence with the GenBank database. The chromosomal location of the GFAP gene is on pig Chr: 12(p11-(2/3)p13) using pig x rodent somatic cell hybrid panel. PMID- 11209707 TI - [Association of microsatellite genomic heterozygosity with inbred pig performance under successive inbreeding]. AB - Genomic scanning using microsatellites was carried out in a pig family that has undergone 5 successive generations of inbreeding. A total of 56 microsatellite markers were utilized, which were derived from swine chromosome 01, 02, 11, 13, 17, 18 and gave a considerable coverage of these chromosomes. Genomic heterozygosity was estimated as an average of marker heterozygosity over all 6 chromosomes. Analysis of variance using a generalized linear model indicated that genomic heterozygosity was positively and significantly associated with slaughter weight (SWT) and average daily slaughter gain (ADSG), but inconsistently and non significantly associated with backfat depth (BFDP). Association effects of GH on SWT and ADSG increased from generation 1 to generation 2, and, then, reduced gradually with generations while levels of inbreeding accumulated. The maximum effect was observed in generation 2, which was estimated to be 22.43 kg for SWT and 0.132 kg/d for ADSG. The effect of marker heterozygosity on SWT and ASDG differed dramatically from chromosome to chromosome: the largest effect was observed with chromosome 13 (i.e. 6.306 kg for SWT and 0.032 kg/d for ADSG), followed by chromosome 01, 17, 18, 02 and 11. Marker heterozygosity was not found to be significantly associated with BFDP for all chromosomes. These results give rise to three implications. First, genes (e.g. QTL) contributing to traits of economic importance are not equally distributed among these chromosomes, which represents the difference in determination of quantitative traits across chromosomes or at DNA level. Second, the association of genomic or marker heterozygosity with pig performance varies from chromosome to chromosome, or with generations of inbreeding. This phenomenon provides an evidence that heterozygosity-performance association is not straight-forward, but rather complex as a result of complicated gene actions and interactions, and sometimes may even be much more complicated when confounded and misled by inabequate or improper markers utilized. Last, decreased heterozygous advantage or heterozygous disadvantage, in some cases, is very much likely as a result of the high linkage disequilibrium under high levels of inbreeding, where one or several deleterious alleles might be linked with neutural markers in much high probability. PMID- 11209708 TI - [QTLs analysis of tiller angle in rice (Oryza sativa L.)]. AB - Tiller angle is one of important characters that constitute plant type with great significance in breading. A pair of japonica/indica lines, which were significantly different in tiller angle, were used in this study. A DH population were constructed via anther culture of F1 hybrids. The tiller angles of 115 DH lines were measured. QTL analysis was conducted based on the constructed molecular linkage map. Three QTLs (qTA-9a, qTA-9b and qTA-12) were detected on chromosome 9 and 12 respectively, Their variation were 22.7%, 11.9% and 20.9% respectively and their additive effects were all negative, showing this character was controlled by genes from big tiller angle parent ZYQ8. The application of the tiller angle that was controlled by major genes and minor genes in rice breeding is also discussed. PMID- 11209709 TI - [Chromosome location of a semidwarf gene sd-t in indica rice (O. sativa L.)]. AB - For investigating the linkage group to which the semidwarf gene sd-t belongs, the crosses between Aitaiyin 2(ATY2), a variety of sd-t carrier in indica rice, and marker stocks as well as the trisomic lines of IR36 were made. The results indicated that the sd-t gene was linked to the marker genes Prp-b (Purple pericap b), lg(ligueless) and Wh(White hull). The recombination values estimated were 2.85% +/- 0.52% for sd-t to Prp-b, 27.90% +/- 3.81% for sd-t to lg and 38.62% +/- 2.99% for sd-t to Wh, respectively. It was inferred that the sd-t gene was located on chromosome 4 according to the established relationship between chromosomes and linkage groups. PMID- 11209710 TI - [Studies of biochemical markers of four isonucleus-alloplasmic lines of common wheat]. AB - The peroxidase isozyme and the soluble peoteins of four isonucleus-alloplasmic lines of common wheat--D2-CA8057 (fertile, BC14), CMS line msD2-CA8057(BC11), CMS line msA-CA8057(BC12), CA8057 (nucleus donor) in different developmental stages were studies by polyacrylamide gel electrophoresis (PAGE) and gradient SDS-PAGE respectively. The peroxidase isozyme of bionucleus-stage anther, milk-stage endosperm and the soluble proteins of bionucleus-stage anther, leaf (the beginning and ending overwinter), dry-seed endosperm among fertile line, msD2 CA8057 and msA-CA8057 were evidently different (but few differences between CA8057 and D2-CA8057). These differences resulted from the pecially-regulated expression of (male-sterile) cytoplasmic genes to nuclear genes and could be used to identify the four isonucleus-alloplasmic lines. These results showed that msD2 CA8057 and msA-CA8057 were two different kinds of new CMS pattern. PMID- 11209711 TI - [Purification and biochemical characterization of high-molecular-weight-glutenin subunits 14 and 15]. AB - The high molecular weight glutenin subunits 14 and 15 were purified from cultivars of bread wheat (Triticum aestivum) Xiaoyan 6 by preparative sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) appled a new method for visualizing protein in gels. N-terminal amino acid sequences were homologous comparing with other High-Molecular-Weight glutenin subunits. The result suggested that they were basic protein analyzed by two-dimensional electrophoresis of IEF(Isoelectric Focussing) x SDS-PAGE and NEPHGE(Non Equilibrium PI-gradient Electrophoresis) x SDS-PAGE. PMID- 11209712 TI - [Development of Triticum aestivum-Haynaldia villosa 6VS ditelosomic substitution line via phlb mutant]. AB - Chinese Spring phlb mutant (C S phlbphlb) was crossed to Triticum aestivum Haynaldia villosa 6V (6A) alien substitution line and F1 back was crossed with C. S phlbphlb. One LV 02 with varied H. villosa 6V chromosome and one LV 02-01 with 40 T. aestivum chromosome, one H. villosa 6V and 6VS chromosome were screened in BC1F1 and BC1F2 respectively by C-banding and the fluorescence in situ hybridization (FISH). In segregated generation of LV 02-01, eight T. aestivum-H. villosa 6VS ditelosomic substitution lines were screened by FISH and C-banding. PMID- 11209713 TI - [Gene analysis of Chinese barley dwarf germplasm resources. II. Location of the dwarf genes on chromosomes]. AB - Twenty dwarf sources of Chinese barley were crossed to a set of marker stocks. Based on the linkage tests with the marker traits and genes, the dwarfing genes in Chinese dwarf barley were located on different chromosomes. Fifteen of the 20 dwarf sources were recessive mono-locus. Among them, BQK carried a pair of dwarfing genes on its short arms of 2(2H) chromosome, linking to the wide outer glume gene w; HZA 77 etc. 10 dwarf sources held dwarfing genes allelic to semi brachytic gene uz on their long arms of 3(3H) chromosomes respectively; 91G318, 91D27, 11012.2 and JJ had dwarfing genes on their long arms of 4(4H) chromosomes, which linked with the hooded awn gene K. The remaining five dwarf sources were two-locus. Two recessive loci were found to be on 2HS and 4HL respectively in DQQK, ZLL and ZLLQK. A pair of incomplete dominant genes were located on 2HS, and another pair of recessive ones located on 3HL in 1974E. Two recessive loci of Yan 66 were separately located on its 3HL and 4HL. PMID- 11209714 TI - [Genetic analysis of mutant genes and RAPD marker of mutant gene of narrow leaflet in soybean]. AB - Mutant E182 with "narrow leaflet-4 seeded pod" was selected from descendents of EMS-treated seeds of soybean variety Lu Dou No. 4 (LD4) with "ovate leaflet without 4 seeded pod". Genetic analyses of F2 individuals of crossing between mutant E182 and parent LD4 indicated that segregation ratio between ovate and narrow leaflet was 3:1, so was segregation ratio between "without 4 seeded pod" and "4 seeded pod". Segregation ratios of four character types in F2 population of 1,654 individuals were beyond 9:3:3:1 of two pairs of independent gene, showing linkage inheritance. Reccmbinant ratio between mutant genes of narrow leaflet and 4 seeded pod was 11.24% +/- 0.81%. On the other hand, mutant E182, parent LD4 and F2, F3 individuals of their hybrids were analyzed by means of RAPD technique. The marker OPY6-1300 linked with the mutant gene of narrow leaflet was generated, and genetic distance of the marker and mutant gene was 8 cent Morgan (cM), being 10 cM nearer than RFLP marker of narrow leaflet generated by shoemaker. PMID- 11209715 TI - [Studies of FISH and karyotype of Gossypium barbadense]. AB - Based on the fluorescent in situ hybridization (FISH) of somatic chromosome of Gossypium barbadense with the probe of genomic DNA (gDNA) of Gossypium arboreum, two sets of chromosomes were easily distinguished by signals hybridized or not. The FISH directly proved that G. barbadense originated from two different diploid species, but was not in concordance with the former point that every chromosome of A sub-genome of tetraploid species was bigger than that of other sub-genome (D genome). The karyotype formula of G. barbadense based on its FISH was 2n = 4x = 52 = 38 m + 14sm(6sat). There were three pairs of satellite chromosomes which were all sm types. Their satellites located in short arms but originated differently from their chromosomes of sub-genome. Fragment translocations occured in the long arms of homologous chromosomes of number 5, 6 and 9 of A sub-genome. It was suggested that the translated fragments come from D sub-genome. The fragments are fairly large with the relative lengths of 19.21%, 17.69% and 12.88% of their whole chromosomes, respectively. At least five pairs of chromosomes in D sub-genome show some hybridized signals of gDNA probe of G. arboreum in their centromere regions, which indicated that there would be chromatin introgressions from A sub-genome. PMID- 11209716 TI - [Molecular analysis of polymorphisms for B-LII beta(beta 1 exon) locus in some Chinese native chicken]. AB - Molecular genetic polymorphisms were studied for MHC-B-LII beta(beta 1 exon) locus in ten breeds of chicken by PCR-RFLPs. Thirty-seven genotypes were detected in these chicken. In the 305 bp fragment derived from MHC-B-LII beta(beta 1 exon) locus digested with Hha I, EcoRV, HaeIII, Xba I, there were significant difference with the frequencies of genotype and combined genotype among individuals or breeds. Statistical results showed Hardy-Weinberg equilibrium in polymorphic sites were inconsistent among various breeds. Sequencing results suggested there are more polymorphism at the level of amino acid than at that of nucleotide. Furthermore, as antigen binding site, the highly polymorphisms of beta 1 exon sequence was a reflection to the antigen diversity of immune systems. Moreover, it was implied that there was highly association between genetic polymorphisms of beta 1 exon and reproduction performance in chicken. PMID- 11209717 TI - Identification of molecular genetic markers tightly linked to downy mildew resistant genes in grape. AB - Bulk segregant analysis (BSA), randomly amplified polymorphic DNA (RAPD) and sequence characterized amplified region (SCAR) methods were used to tag the downy mildew-resistant genes of grape with molecular markers. Parents and their 60 individuals of an F1 progeny resulting from a cross 88-110 between 83-4-96 (Vitis quinquangularis, downy mildew-resistant) and Muscat Rose (V. vinifera, downy mildew-susceptible), three F2 progenies resulting from three crosses of self cross and inter-cross of 88-110 F1 seedlings, as well as another interspecific F1 hybrids of 88-84 cross [Xun-3 (V. quinquangularis, downy mildew-resistant) x Ugni Blanc (V. vinifera, downy mildew-susceptible)] and the wild grapes native to China were used for the study. Among 280 Operon primers, 160 gave distinct band patterns. One RAPD marker OPO06-1500 was tightly linked to a major gene resistant to Plasmopara viticola (RPv-1). Based on Mapmaker software analysis, the map distance between RPv-1 and OPO06-1500 was 1.7 cM. Marker OPO06-1500 was cloned and sequenced. According to the sequence, two specific primers were designed to amplify all plant materials. RAPD marker was converted into SCAR marker (SCO06 1500). One distinct single band only in resistant plants was amplified, whose size was the same as that of the RAPD marker. The SCAR marker's popularity was confirmed, and it could be used for the identification of hybrid resistant to P. viticola and will be potentially useful in the development of new resistant grape cultivars. PMID- 11209718 TI - [A new method for constructing linkage maps of molecular markers: three-point selfcross method]. AB - The method for constructing linkage maps has almost been so far the three-point testcross in higher organisms. This method is, however, considerably limited to a requirement of a parent or line with three recessive genes that can be obtained by only cross breeding. In this paper, the three-point selfcross method for mapping was proposed. This method can also provide us with informations of mapping as the same as the three-point testcross method. However, the three-point selfcross method does not have any limitation of requiring a parent with three recessive genes. It was theoretically proved that this method could be used to map molecular marker loci in small sample of F2 population. Exactly to test both the methods for mapping, Fisher information content was applied to prove that the three-point selfcross method is powerful for mapping. Further to test this method, data of the first 6 loci were chosen from 12 RFLP loci detected in 333 F2 individuals in SAMPLE. RAW file in MAPMAKER/EXP version 3.0 that Lander et al. (1987) provided. The result showed that, like MAPMAKER program, the three-point selfcross method is powerful to detect linkage relationship among loci, to order them on linkage groups and to calculate distances between nearest neighbor loci. Besides, this method could provide us with the other information of map such as the positive or negative interference and couple or repulsion configuration. PMID- 11209719 TI - [Ad multos annos. 30 years of sonographic tissue characterization]. PMID- 11209720 TI - [Renal artery stenosis: screening, diagnostic and therapeutic options]. AB - Hypertension is a frequent disease and renal artery stenosis, as a potential cause of hypertension, can be cured. Therefore, we frequently need to exclude a renal artery stenosis in patients with hypertension in our daily routine. This calls for a screening procedure which is non-invasive, highly effective and not too expensive. This paper describes the advantages and limitations of colour Doppler ultrasound in diagnosing renal artery stenosis. Colour Doppler ultrasound with intrarenal Doppler analysis is an ideal tool in the screening for relevant renal artery stenosis in patients with hypertension. This technique, however, requires a careful approach and extrarenal abnormalities need to be considered. PMID- 11209721 TI - [Computer-supported tissue characterization in musculoskeletal ultrasonography]. AB - A new diagnostic system combining conventional gray-scale ultrasonography (US) and computer-assisted texture analysis of sonograms makes it possible to differentiate more easily between specific neuromuscular diseases. The first step involves myosonography with strictly standardized US. In a group of 72 patients with histologically and molecular-genetically confirmed diagnosis 63 patients (88%) were diagnosed by conventional US as having Duchenne's muscular dystrophy, spinal muscular atrophy, hereditary sensomotor neuropathy or inflammatory myopathy. Secondly, in a double blind setting computer-assisted texture analysis was used on the same sample of subjects. Tissue Texture can be characterized by the brightness as well as the micro- and macro-structure of the tissue. The use of these parameters leads to a sensitivity of 77 to 94% and a specificity of 81 to 98%. In conclusion, the combination of both techniques allows us to avoid invasive diagnostic procedures in a substantial group of patients. PMID- 11209722 TI - [Evaluation of doppler ultrasonography criteria for the differential diagnosis of pancreatic tumors]. AB - AIM: In order to improve the differential diagnosis of pancreatic lesions, dopplersonographic criteria for the tumours were evaluated. METHODS: 35 patients diagnosed by conventional ultrasound as having a tumour of pancreas were further investigated by B-mode sonography, fundamental and echo-enhanced power-Doppler sonography focusing on specific properties of the tumours. The results were correlated to the histological findings. RESULTS: Ductal carcinomas and cystadenocarcinomas are often hypovascularized in comparison to the surrounding tissue. In contrast to this, neuroendocrine tumours and cystadenomas are mostly hypervascularized. Tumours associated with pancreatitis show different vascularization patterns depending on inflammation and the extent of necrosis. CONCLUSIONS: Pancreatic tumours display different vascularization patterns in the echo-enhanced power-Doppler sonography. These characteristics can be useful for the differential diagnosis of pancreatic tumours. PMID- 11209723 TI - [Doppler ultrasonographic diagnosis of increased intracranial pressure by comparison of flow velocities in the extra- and intracranial secitons of the internal carotid artery]. AB - AIM: By comparison of the flow velocities in the intracranial and extracranial parts of the internal carotid artery the influence of an increased intracranial pressure on cerebral perfusion can be determined. Aim of the study was to establish normal values in healthy infants not displaying clinical signs of increased intracranial pressure. METHOD: 108 healthy infants (35 girls, 73 boys) with a gestational age of 42 +/- 14 weeks and a weight of 2440 +/- 2310 g were investigated. In all infants Doppler sonographic flow measurements were performed within the petrosal part (extracranial) and the cerebral part (intracranial) of the internal carotid artery. From the flow profile the peak systolic (Vs), enddiastolic (Ved) and time average (TAV) flow velocities were estimated. In all infants the I/E-ratio of the intracranial and extracranial flow velocities was calculated. RESULTS: Flow velocities within the intracranial section of the vessel were lower than in the extracranial part, due to the greater angle of incidence (33 +/- 8 degrees) between the pars cerebralis and the Doppler beam. In the pars petrosa of the internal carotid artery Vs was 59.7 +/- 21.4, Ved 14.6 +/ 9.5 and TAV 17.2 +/- 11.8 cm/sec. Within the pars cerebralis Vs was 48.8 +/- 22.1, Ved 12.3 +/- 8.4 and TAV 12.9 +/- 7.5 cm/sec. I/E-ratio of intracranial and extracranial flow velocities was 0.83 +/- 0.14 for Vs, 0.88 +/- 0.29 for Ved and 0.82 +/- 0.24 for TAV. CONCLUSION: The relation between intracranial and extracranial flow velocities within the internal carotid artery as described by the I/E-ratio is constant. Alterations of the flow velocities intracranially such as in cases of increased intracranial pressure, may cause changes of the I/E ratio. Determining the I/E-ratio may be a valuable method for the assessment of increased intracranial pressure. PMID- 11209724 TI - [Laparoscopic intraoperative differential diagnosis of adnexal tumors. A pilot study of 20 premenopausal patients]. AB - AIM: The purpose of the study was to determine the feasibility and potential clinical value of laparoscopic intraoperative sonography in the female genital tract. PATIENTS AND METHOD: Intraoperative ultrasound was performed in 20 consecutive premenopausal patients with adnexal masses during laparoscopy using a 7.5 MHz semiflexible transducer. RESULTS: Laparoscopic ultrasound of the female genital tract improves image resolution. Furthermore, this new method allows accurate localisation of early tubal pregnancy and may be helpful if laparoscopic evaluation of the inner genital tract is impaired by severe adhesions. In 7 out of 20 patients, the therapeutical procedure was clearly influenced by the laparoscopic ultrasound findings, resulting in a benefit for the patients in all seven cases. CONCLUSION: Intraoperative laparoscopic ultrasound may improve minimal invasive management of adnexal masses. PMID- 11209725 TI - [Amplitude-coded color doppler ultrasonography in pediatrics]. AB - OBJECTIVE: The goal of this study was to evaluate the use of amplitude coded colour Doppler sonography (aCDS) in infants and children. METHODS: We analysed our own experiences in 270 patients (mean age: 6.3 years, range: newborn--16 years) with various paediatric aCDS applications. The aCDS results of 460 individual investigations were correlated with conventional CDS results, clinical findings and the results of other imaging modalities. Additionally, relevant literature is reviewed and discussed. RESULTS: ACDS is a valuable tool in paediatric sonography. It enriches the diagnostic field of ultrasound, particularly in regard to renal, abdominal, oncological and small part applications. ACDS could successfully be performed in 92.4% of investigations. Overall accuracy was 86.6% (in regard to the total number), sensitivity was 92% (calculated for the number of successful investigations), additional diagnostic information was gained in 18.6% to 48% of patients--depending on the field of application. CONCLUSION: ACDS is applicable to the majority of infants and children, in spite of the risk of motion artefacts. It is a valuable addition to conventional paediatric ultrasound and colour Doppler sonography. In conjunction with new modalities like three-dimensional sonography, harmonic imaging and ultrasound contrast agents it promises to continuously widen sonographic diagnostic potential. PMID- 11209726 TI - Do we need MR images for diagnosing tendon ruptures of the distal biceps brachii? The value of ultrasonographic imaging. AB - AIM: To assess the usefulness of ultrasound in the diagnosis of rupture of the distal biceps brachii muscle by demonstrating the clear differentiation between the distal biceps muscle and the surrounding soft tissue in a standardized section of the elbow. METHOD: Under sonographic guidance five biceps muscles of three cadavers were marked with a needle in the region of the elbow joint. Thereafter an anatomical preparation of the distal biceps brachii muscle followed to verify the correct positioning of the needle. Real time ultrasound was performed with a 7.5 MHz linear array transducer. The standard section of the elbow and the images on the screen correspond to the guidelines provided by the German Society of Ultrasonography in the Locomotor Apparatus (DEGUM). RESULTS: In all five cases the needle tip could be found in the middle of the distal biceps muscle. It was possible to perform a sonographically guided puncture of the muscle and to differentiate between distal biceps brachii and surrounding soft tissues using a high resolution transducer of the newest generation in ultrasound technology. CONCLUSION: Our investigation confirmed our clinical ultrasound findings in distal biceps tendon ruptures. The echo-intense signal is replaced by a hypoechogenic signal representing the haematoma in the area of the distal biceps brachii muscle. In addition to the clinical examination in case of a ruptured distal biceps muscle ultrasound of the elbow is a valuable and reliable imaging method to support the diagnosis. MRI of the elbow is not always necessary to confirm the diagnosis. PMID- 11209727 TI - Sonographic imaging of a spinoglenoid cyst. AB - Spinoglenoid cysts can be the reason for suprascapular nerve entrapment syndrome resulting an isolated atrophy of the infraspinatus muscle. The syndrome usually presents painless and is frequently observed in professional volleyball players. The incidence of these cysts in volleyballplayers is still unknown. Diagnosis is made by neurological examination using electromyography and magnetic resonance imaging. Our case shows the potential of ultrasound as a possible imaging method of ganglion cysts that could be used as a screening method to prevent suprascapular neuropathy. PMID- 11209728 TI - [Tips and ticks: intrarenal doppler ultrasonography in the diagnosis of renal artery stenosis]. PMID- 11209729 TI - [Ultrasonography in gastroenterology. Report on the seminar at Euroson School, 12 15 July 2000]. PMID- 11209730 TI - [Hypotheses and facts]. PMID- 11209731 TI - [ACUTE, TACTICS, TARGET, GUSTO-IV, MIRACL, COPERNICUS and Vel-HeFT. New study results in cardiology]. PMID- 11209732 TI - [A drug for smoking cessation?]. PMID- 11209733 TI - [Forms of thrombophilia and their treatment]. PMID- 11209734 TI - Progesterone receptor modulators at the start of a new millennium. PMID- 11209735 TI - [Organization of early detection of patients with tuberculosis in Moscow]. AB - The tuberculosis mortality rate is largely determined by the organization of early identification of patients with this disease in the general population. At present the volume of prophylactic surveys has reduced, but, nevertheless, they are the method of choice in detecting tuberculosis in time. Since the prevalence of tuberculosis greatly differs in different populations, prophylactic examinations must be differential in relation to the risk of disease or epidemiological hazards. Increasing the coverage of prophylactic examinations of risk groups by 10% allows one to increase the identification of patients with tuberculosis by 1.6 times in them, that by 8.0% enhances it by 1.9 times. Since the socioeconomic conditions have changed and the logistics is poor, the most effective existing actions should be taken. PMID- 11209736 TI - [Detection of pulmonary tuberculosis in general health care facilities]. AB - The paper deals with medical aspects how to organize the detection of tuberculosis in all populations. It is stressed that it is necessary now to enhance activities in polyclinics by increasing the quality of examination of those who visit doctors. The specialized service must reorganize its work with tuberculosis risk groups by enhancing organizational measures and increasing the quality of examination. PMID- 11209737 TI - [Detection of patients with respiratory tuberculosis in high-risk groups ar general polyclinic]. AB - The paper presents the results of elucidation of numerous tuberculosis risk factors. Eight most significant criteria were selected by using the multifactorial analysis. They were used to develop an algorithm for selecting patients in risk groups at the polyclinic. Follow-ups of these groups of patients were shown to enhance the detection rate of tuberculosis, thus greatly reducing material expenditures. PMID- 11209738 TI - [Problems in modernization of Russian fluorographic service]. PMID- 11209739 TI - [Comparative assessment of diagnostic capacities of thoracic fluorography, film x ray study and small-dose digital x-ray study]. AB - The efficiency of small-dose digital X-ray study (SDDXRS) of the chest versus film X-ray study (FXRS) and fluorography was studied during prophylactic surveys. SDDXRS competes only with FXRS in evaluating the normal anatomic structures and it compares much favourably with fluography. In chest abnormalities, SDDXRS, unlike FXRS, cannot reveal fine linear shadows, detect bullae in the lung, the upper margin of pleural exudates, changes in the bones worse, but shows soft focal shadows of the decay cavity, abnormal changes behind the shadow of the heart. The efficiency of SDDXRS was superior to fluography in detecting tuberculosis in all points, at the same time SDDXRS virtually have no spoilage that is about 18% at fluography. PMID- 11209740 TI - [Problems in standartization of population fluorographic screening]. AB - The authors have developed the methodology and techniques for standardizing fluorographic screening by using computed technology. The proposed does not require any manually written registration, the accounting of both patient and fluorogram in-and-outflows, the keeping on-going medical documents and paper archives. At the same time the technique allows one to form computerized lists, the dates of patients' visits, to control radiologists' activities, to supervise control over the use of hospital and mobile equipment, to plan expendable materials, etc. The efficiency and novelty of the technology are based on the computerization to make a diagnosis, and to set up a centralized bank of data on patients. This provides favorable conditions for continuous monitoring of fluographic screening of the population at any level of management and administration. PMID- 11209741 TI - [Tuberculosis in internist's practice]. PMID- 11209742 TI - [Potentialities of immunochromatographic technique in detection of tuberculosis]. PMID- 11209743 TI - [Improvement of epidemiological analysis in tuberculous infection]. PMID- 11209744 TI - [Tuberculosis mortality in Sverdlovsk Region]. AB - Tuberculosis mortality is 9.3 times higher in men than in women. Women more commonly recover and less frequently die from progressive tuberculosis. The main causes of death are fibrocavernous or infiltrative tuberculosis, and caseous pneumonia. In young people, the most common cause of death is tuberculosis of the meninga or central nervous system, women more frequently die from caseous pneumonia. Prisoners more commonly die from infiltrative tuberculosis and more rarely from fibrocavernous tuberculosis than the general population of Sverdlovsk. The most common causes of death of patients with tuberculosis who die in the first year of its diagnosis are caseous pneumonia and fibrocavernous tuberculosis. The factors predisposing to poor prognosis were late detection of the disease, treatment refusal, severe concomitant diseases, and intolerance of antituberculous agents. PMID- 11209746 TI - [Endocrinological parameters of patients with acute progressive pulmonary tuberculosis]. AB - Examining the levels of the hormones insulin and cortisole that play a significant role in nonspecific protection in tuberculosis indicates the heterodirectional pattern of changes in endocrinological parameters in relation to the clinical form of acute progressive tuberculosis. In drug-treated patients with caseous pneumonia, the high level of cortisole decreased and the content of insulin reached the lower normal range with 18.2% of cases having hypoinsulinemia. Patients with disseminated pulmonary tuberculosis had an inversely proportion ratio of the hormones, which reflected the specific features of acute progression of this clinical form. In acute progressive infiltrative tuberculosis, the levels of cortisole and insulin significantly increased during chemotherapy. Nevertheless, whatever changes were observed in hormonal levels, variations in the parameters indicate the long-term activity of specific inflammation in acute progressive pulmonary tuberculosis. PMID- 11209745 TI - [Liver function at the stage of intensive tuberculosis treatment of patients with diabetes mellitus]. AB - Intensive pulmonary tuberculosis treatment was performed in 65 patients with this disease concurrent with diabetes according to the WHO recommendations. Among them there were 44 new cases and 21 cases with relapse. Comparing the hepatic functional parameters before the first intensive stage of treatment and after its termination (following 2-3 months) showed a regular and statistically significant increase in the activity of aminotransferases and a clear tendency for increases in the values of total bilirubin and thymol tests. These changes were equally pronounced with both treatment regimens in patients with types both I and II diabetes mellitus and within normal ranges and allowed the drug treatment regimens to be continued. PMID- 11209747 TI - Enabling guidelines for computer-based decision support. PMID- 11209748 TI - Apolipoprotein B versus lipoprotein lipids: vital lessons from the AFCAPS/TexCAPS trial. PMID- 11209749 TI - Circadian rhythms of sterol 12alpha-hydroxylase, cholesterol 7alpha-hydroxylase and DBP involved in rat cholesterol catabolism. AB - Circadian rhythms of important enzymes involved in the conversion of cholesterol to bile acids [sterol 12alpha-hydroxylase (12alpha-hydroxylase) and cholesterol 7alpha-hydroxylase (7alpha-hydroxylase)] and an albumin site D-binding protein (DBP) were examined in rats. When the animals were fed freely, they usually ate in the dark and the circadian rhythms of activities of 12alpha-hydroxylase and 7alpha-hydroxylase showed the same peaks (at 10 p.m.) and lows (at 2 p.m.). Their mRNA levels were determined at four timepoints: 3 a.m., 10 a.m., 3 p.m. and 10 p.m. A maximum of the rhythm of 12alpha-hydroxylase was observed at 3 p.m. and the minimum at 3 a.m. These results are distinct from those of 7alpha hydroxylase, whose maximum point was at 10 p.m. and minimum at 3 p.m. When the rats were fed only in the day-time (from 9 a.m. to 5 p.m.), a marked shift of the activity and mRNA rhythms was observed with both enzymes. The circadian rhythms of the activities of both enzymes showed the same peaks (at 3 p.m.), but the mRNA levels of 12alpha-hydroxylase were distinct from those of 7alpha-hydroxylase, whose maximum point was at 3 a.m. and minimum at 10 p.m. Differences between the maximum and the minimum points of each enzyme mRNA level were statistically significant (P < 0.01 for 12alpha-hydroxylase and 0.05 for 7alpha-hydroxylase). Moreover, circadian rhythms of DBP were also markedly shifted with the change of feeding period. The maximum mRNA level was observed at 10 p.m. instead of 10 a.m. and the minimum was at 10 a.m. instead of 10 p.m. PMID- 11209750 TI - Mannosidase action, independent of glucose trimming, is essential for proteasome mediated degradation of unassembled glycosylated Ig light chains. AB - In order to study the role of N-glycans in the ER-associated degradation of unassembled immunoglobulin light (Ig L) chains, we introduced N-glycan acceptor sites into the variable domain of the murine Ig L chain kappaNS1, which is unfolded in unassembled molecules. We investigated the fate of kappaNS1 glycosylated at position 70 (K70) and of a double mutant (kappa18/70) in stably transfected HeLa cells. Degradation of both chains was impaired by lactacystin, a specific inhibitor of the proteasome. The mannosidase inhibitor dMNJ also blocked degradation in a step preceding proteasome action, as did two protein synthesis inhibitors, cycloheximide and puromycin. In contrast, ER glucosidase inhibitors dramatically accelerated the degradation of the chains when added either pre- or posttranslationally. The accelerated degradation was sensitive to lactacystin, dMNJ and cycloheximide, too. None of these drugs, except lactacystin, affected the degradation of unglycosylated kappaNS1 chains. We conclude that ER mannosidases and proteasome activities, but not glucose trimming (and therefore, most likely not the calnexin/calreticulin UDP:glucose glycoprotein glucosyl transferase cycle), are essential for ER-associated degradation (ERAD) of soluble glycoproteins. A role for a short-lived protein, acting before or simultaneously to ER mannosidases, is suggested. PMID- 11209751 TI - Characterization of a receptor for heat shock protein 70 on macrophages and monocytes. AB - Heat shock proteins (Hsps) and molecular chaperones isolated from tumors or virally infected cells elicit an efficient CD8+ T cell response against bound antigenic peptides. This immune response is mediated by presentation of the peptides on MHC class I complexes of antigen-presenting cells (APCs), but the cellular mechanism of this presentation process is not yet understood. Here we provide evidence for the existence of a proteinaceous receptor on the surface of APCs that is specific for mammalian Hsp70. Using a flow cytometry-based assay, saturable binding of Hsp70 to the cell surface of macrophages and peripheral blood monocytes, but not of lymphocytes, can be demonstrated. The affinity of the receptor is in the sub-micromolar range (Kd < 100 nM). Only mammalian Hsc70/Hsp70, but not bacterial Hsp70, is bound with high affinity. Subsequent to binding, Hsp70 is taken up by endocytosis, resulting in an intracellular localization. Our results suggest that receptor-mediated endocytosis forms the basis for the demonstrated efficacy of Hsp70-peptide complexes as anti-tumor vaccines. PMID- 11209752 TI - Yeast translational activator Cbs2p: mitochondrial targeting and effect of overexpression. AB - The yeast translational activator protein Cbs2p is imported into mitochondria without obvious proteolytic processing. To test the importance of amino-terminal amino acids for mitochondrial targeting we fused varying portions of the N terminus with green fluorescent protein and examined the intracellular distribution of the reporter protein. We show that the 25 N-terminal amino acids are sufficient to direct the majority of the fusion protein into mitochondria. Cbs2p derivatives lacking 9 to 35 amino acids from the N-terminus fail to complement the respiratory deficiency of a deltacbs2 strain, but are still imported into mitochondria. Therefore Cbs2p contains at least one independent mitochondrial targeting information in addition to the N-terminal signal. We further analyzed the effect of over-expression of Cbs2p on mitochondrial function. Elevated concentrations of Cbs2p lead to slightly impaired mitochondrial gene expression, probably as the result of the formation of inactive Cbs2p aggregates. PMID- 11209753 TI - Mutational scanning of a hairpin loop in the tryptophan synthase beta-subunit implicated in allostery and substrate channeling. AB - The tryptophan synthases from Escherichia coli and Salmonella typhimurium are tetrameric enzymes, with an elongated TrpA.TrpB.TrpB.TrpA structure. Structural studies have identified residues 277-283 of TrpB as a potentially important region for the allosteric communication between the TrpA and TrpB subunits and for the transport of indole between their active sites through a hydrophobic tunnel. To explore the functional role of this region, we analyzed the effects of 19 single and double mutations in TrpB on the tryptophan synthase (TSase) and serine deaminase (SDase) activities of the TrpB2 dimer, either in the presence or in the absence of the TrpA subunit. The mutations of residues 273-283 could be divided into 4 classes. Mutations 1278A, F280G and M282A decreased the SDase and TSase activities of TrpB2 to similar extents. F280A decreased the SDase activity of TrpB2 more than its TSase activity, whereas the reverse was true for Y279L. F280A decreased the activation factor of TrpB2 by TrpA, whereas F280G increased it. The reaction steps and intramolecular contacts that could be affected by the mutations are described. The sequence 278-IYFGM-282, which is present in E. coli and S. typhimurium, is only found in 5 out of 42 organisms, whereas the sequence VLHGX is found in 21 organisms. Our results identified several mutations that could be used as structural probes to analyze precisely the roles of residues 278 282 and their evolution. PMID- 11209754 TI - The difference in the carboxy-terminal sequence is responsible for the difference in the activity of chicken and rat liver fructose-2,6-bisphosphatase. AB - The fructose-2,6-bisphosphatase domain of the bifunctional chicken liver enzyme 6 phosphofructo-2-kinase/fructose-2,6-bisphosphatase shares approximately 95% amino acid sequence homology with that of the rat enzyme. However, these two enzymes are significantly different in their phosphatase activities. In this report, we show that the COOH-terminal 25 amino acids of the two enzymes are responsible for the different enzymatic activities. Although these 25 amino acids are not required for the phosphatase activity, their removal diminishes the differences in the activities between the two enzymes. In addition, two chimeric molecules (one consisting of the catalytic core of the chicken bisphosphatase domain and the rat COOH-terminal 25 amino acids, and the other consisting of most of the intact chicken enzyme and the rat COOH-terminal 25 amino acids) showed the same kinetic properties as the rat enzyme. Furthermore, substitution of the residues Pro456Pro457Ala458 of the chicken enzyme with GluAlaGlu, the corresponding sequence in the rat liver enzyme, yields a chicken enzyme that behaves like the rat enzyme. These results demonstrate that the different bisphosphatase activities of the chicken and rat liver bifunctional enzymes can be attributed to the differences in their COOH-terminal amino acid sequences, particularly the three residues. PMID- 11209755 TI - Crystal structure of the caspase activator human granzyme B, a proteinase highly specific for an Asp-P1 residue. AB - Granzyme B is the prototypic member of the granzymes, a family of trypsin-like serine proteinases localized in the dense cytoplasmic granules of activated natural killer cells and cytotoxic T lymphocytes. Granzyme B directly triggers apoptosis in target cells by activating the caspase pathway, and has been implicated in the etiology of rheumatoid arthritis. Human granzyme B expressed in a baculovirus system has been crystallized without inhibitor and its structure has been determined to 3.1 A resolution, after considerably improving the diffraction power of the crystals by controlled humidity changes. The granzyme B structure reveals an overall fold similar to that found in cathepsin G and human chymase. The guanidinium group of Arg226, anchored at the back of the S1 specificity pocket, can form a salt bridge with the P1-Asp side chain of a bound peptide substrate. The architecture of the substrate binding site of granzyme B appears to be designed to accommodate and cleave hexapeptides such as the sequence Ile-Glu-Thr-Asp-/Ser-Gly present in the activation site of pro-caspase 3, a proven physiological substrate of granzyme B. These granzyme B crystals, with fully accessible active sites, are well suited for soaking with small synthetic inhibitors that might be used for a treatment of chronic inflammatory disorders. PMID- 11209756 TI - Primary structure of potato kunitz-type serine proteinase inhibitor. AB - The serine proteinase inhibitor (PSPI-21) isolated from potato tubers (Solanum tuberosum L.) comprises two protein species with pI 5.2 and 6.3, denoted as PSPI 21-5.2 and PSPI-21-6.3, respectively. They were separated by anion exchange chromatography on a Mono Q FPLC column. Both species tightly inhibit human leukocyte elastase, whereas their interaction with trypsin and chymotrypsin is substantially weaker. The sequences of both PSPI-21-5.2 and PSPI-21-6.3 were determined by analysis of overlapping peptides obtained from the oxidized or reduced and S-pyridylethylated proteins after digestion with trypsin or pepsin. Both species of PSPI-21 are composed of two chains, named chains A and B, which are linked by a disulfide bridge between Cys(146) and Cys(157). The other disulfide bridge is located within the A chains between Cys(48) and Cys(97). The amino acid sequences of the large A chains of the two forms, consisting of 150 amino acids residues each, differ in a single residue at position 52. The small chains B, containing 37 and 36 residues in PSPI-21-6.3 and PSPI-21-5.2, respectively, have nine different residues. The entire amino acid sequences of the two inhibitors show a high degree of homology to the other Kunitz-type proteinase inhibitors from plants. PMID- 11209757 TI - Activation of proPHBSP, the zymogen of a plasma hyaluronan binding serine protease, by an intermolecular autocatalytic mechanism. AB - The hyaluronic acid binding serine protease (PHBSP), an enzyme with the ability to activate the coagulation factor FVII and the plasminogen activator precursors and to inactivate factor VIII and factor V, could be isolated from human plasma in the presence of 6M urea as a single-chain zymogen, whereas under native conditions only its activated two-chain form was obtained. The total yield of proenzyme (proPHBSP) was 5-6 mg/l, corresponding to a concentration of at least 80-100nM in plasma. Upon removal of urea, even in the absence of charged surfaces a rapid development of amidolytic activity was observed that correlated with the appearance of the two-chain enzyme. The highest activation rate was observed at pH 6. ProPHBSP processing was concentration-dependent following a second order kinetic and was accelerated by catalytic amounts of active PHBSP, indicating an intermolecular autocatalytic activation. Charged macromolecules like poly-L lysine, heparin, and dextran sulfate strongly accelerated the autoactivation, suggesting that in vivo proPHBSP activation might be a surface-bound process. The intrinsic activity of the proenzyme was determined to be 0.25-0.3%, most likely due to traces of PHBSP. The presence of physiological concentrations of known plasma inhibitors of PHBSP, like alpha2 antiplasmin and C1 esterase inhibitor, but not antithrombin III/heparin, slowed down zymogen processing. Our in vitro data suggest that the autoactivation of proPHBSP during plasma fractionation is induced by the removal of inhibitors of PHBSP and is accelerated by charged surfaces of the chromatographic resins. PMID- 11209758 TI - Human and rat dipeptidyl peptidase III: biochemical and mass spectrometric arguments for similarities and differences. AB - Dipeptidyl peptidase (DPP III) was purified from rat and human erythrocytes using an identical procedure. Electrophoretic analyses revealed the same molecular size and pI for both enzymes. The molecular mass of the human enzyme, measured by matrix-assisted laser desorption/ionization MS, was 82500+/-60 Da. Its tryptic peptide mass profile was determined using the same technique, and the amino acid sequence of two internal peptides was obtained by tandem MS and Edman degradation. A search of databases revealed a high similarity between the human erythrocyte and rat liver DPP III: 21 matches out of 34 detected peptides were found, covering 40% of the total sequence. Matched peptides included the peptide harboring the characteristic HELLGH sequence motif, and a stretch of 19 identical amino acids, containing Glu, a putative ligand of active site zinc. Both enzymes preferred Arg-Arg-2-naphthylamide, and were activated by micromolar Co2+, differing in their pH optima and kcat/Km. Zn2+ ions, sulfhydryl reagents, and aminopeptidase inhibitors, especially probestin, inhibited the rat DPP III more potently. The two enzymes showed the highest affinity for angiotensin III (Ki < 1 microM) and a preference for ahydrophobic residue at the P1' site. However, significant differences in the binding constants for several peptides indicated non-identity in the active site topography of human and rat erythrocyte DPP III. PMID- 11209759 TI - Recombinant anti-stefin A Fab fragment: sequence analysis of the variable region and expression in Escherichia coli. AB - Human stefin A is an inhibitor of lysosomal cysteine proteinases cathepsin B, H, L and S. In the present report we describe the cloning and expression of anti stefin A Fab fragment A22 in E. coli. We have determined the nucleotide sequences of the antibody heavy and light chain and compared them to the murine immunoglobulin germ line sequences. Expression of the two antibody chains was achieved using a single vector with a PhoA promoter and coding regions placed after the signal sequences, directing them to the periplasmic space. The A22 Fab fragment was extracted from the periplasmic space and expression was confirmed by Western blot analysis. The recombinant A22 Fab fragment had an affinity for stefin A comparable to the original monoclonal antibody, as determined by ELISA. PMID- 11209760 TI - Green fluorescent protein photobleaching: a model for protein damage by endogenous and exogenous singlet oxygen. AB - Characterization of protein damage during photosensitization of chlorin e6 treated cells was performed using the green fluorescent protein (GFP). The GFP chromophore damage caused by singlet oxygen was studied in COS 7 kidney cells and E. coli bacteria following light irradiation. Electron spin resonance (ESR) revealed the generation of endogenous singlet oxygen (1O2) by photoactivated GFP, an effect similar to that produced by the exogenous photosensitizer chlorin e6. A light dose-dependent photobleaching effect of GFP was pronounced at low pH or upon photosensitization with chlorin e6. However, the 1O2 quenchers beta-carotene and sodium azide minimized GFP photo-bleaching. Gel electrophoresis of photosensitized GFP followed by fluorescence multi-pixel spectral imaging revealed the binding of chlorin e6 to GFP, affecting the photobleaching efficacy. Fluorescence multi-pixel spectral imaging of GFP-transfected COS 7 cells demonstrated the presence of GFP in the cytoplasm and nucleus, while chlorin e6 was found to be concentrated in the perinuclear vesicles. Exposure of the cells to light induced GFP photobleaching in the close vicinity of chlorin e6 vesicles. We conclude that photoactivated GFP generates endogenous 1O2, inducing chromophore damage, which can be enhanced by the cooperation of exogenous chlorin e6. PMID- 11209761 TI - 193 nm photolysis of aromatic and aliphatic dipeptides in aqueous solution: dependence of decomposition quantum yield on the amino acid sequence. AB - The values of molar absorption coefficient and quantum yields of photodecomposition and peptide bond scission were determined for a number of aromatic and aliphatic dipeptides under 193 nm laser irradiation in neutral argon saturated aqueous solution. Under these conditions we could show that no dependence of the dipeptide decomposition quantum yield on the sequence of amino acid residues exists, neither for aromatic dipeptides nor for aliphatic ones. PMID- 11209762 TI - NADPH:Protochlorophyllide oxidoreductase uses the general import route into chloroplasts. AB - Chloroplast differentiation in angiosperm plants depends on the light-dependent conversion of protochlorophyllide to chlorophyllide by NADPH:protochlorophyllide oxidoreductase (PORA; EC 1.6.99.1), a nuclearly encoded protein. The protein import of the precursor form of PORA into plastids was shown previously to strictly depend on the presence of its substrate protochlorophyllide. PORA seemed to follow a novel, posttranslationally regulated import route. Here we demonstrate that the precursor of PORA from barley is imported into isolated barley plastids independently of protochlorophyllide. PORA as well as PORB import is competed for by the precursor of the small subunit of Rubisco. The data demonstrate that the PORA precursor uses the general import pathway into plastids. Furthermore, en route into chloroplasts the pea POR precursor can be cross-linked to the protein import channel in the outer envelope Toc75 from pea. PMID- 11209763 TI - Superoxide reactivates nitric oxide-inhibited catalase. AB - Catalase binds nitric oxide (NO) to generate ferricatalase-NO, an inhibited form of the enzyme. Superoxide (O2-) is also an inactivator of the enzyme. We found, however, that O2- efficiently converted the inhibited ferricatalase-NO to the active ferricatalase without producing detectable intermediates. The reaction slowed down when O2- was disproportionated to H2O2 and O2 by superoxide dismutase, but H2O2 could displace the heme-bound NO slowly to regenerate ferricatalase. Reactivation was observed even under simultaneous generation of NO and O2-, suggesting that ferricatalase-NO reacts with O2- fast enough to compete with the rapid reaction of O2- and NO. Formation of peroxynitrite by the simultaneous generation of NO and O2- was only partially inhibited by ferricatalase, presumably due to slow binding of NO to catalase in comparison with the reaction of NO and O2-. PMID- 11209764 TI - Perspective: gene divergence, population divergence, and the variance in coalescence time in phylogeographic studies. AB - Molecular methods as applied to the biogeography of single species (phylogeography) or multiple codistributed species (comparative phylogeography) have been productively and extensively used to elucidate common historical features in the diversification of the Earth's biota. However, only recently have methods for estimating population divergence times or their confidence limits while taking into account the critical effects of genetic polymorphism in ancestral species become available, and earlier methods for doing so are underutilized. We review models that address the crucial distinction between the gene divergence, the parameter that is typically recovered in molecular phylogeographic studies, and the population divergence, which is in most cases the parameter of interest and will almost always postdate the gene divergence. Assuming that population sizes of ancestral species are distributed similarly to those of extant species, we show that phylogeographic studies in vertebrates suggest that divergence of alleles in ancestral species can comprise from less than 10% to over 50% of the total divergence between sister species, suggesting that the problem of ancestral polymorphism in dating population divergence can be substantial. The variance in the number of substitutions (among loci for a given species or among species for a given gene) resulting from the stochastic nature of DNA change is generally smaller than the variance due to substitutions along allelic lines whose coalescence times vary due to genetic drift in the ancestral population. Whereas the former variance can be reduced by further DNA sequencing at a single locus, the latter cannot. Contrary to phylogeographic intuition, dating population divergence times when allelic lines have achieved reciprocal monophyly is in some ways more challenging than when allelic lines have not achieved monophyly, because in the former case critical data on ancestral population size provided by residual ancestral polymorphism is lost. In the former case differences in coalescence time between species pairs can in principle be explained entirely by differences in ancestral population size without resorting to explanations involving differences in divergence time. Furthermore, the confidence limits on population divergence times are severely underestimated when those for number of substitutions per site in the DNA sequences examined are used as a proxy. This uncertainty highlights the importance of multilocus data in estimating population divergence times; multilocus data can in principle distinguish differences in coalescence time (T) resulting from differences in population divergence time and differences in T due to differences in ancestral population sizes and will reduce the confidence limits on the estimates. We analyze the contribution of ancestral population size (theta) to T and the effect of uncertainty in theta on estimates of population divergence (tau) for single loci under reciprocal monophyly using a simple Bayesian extension of Takahata and Satta's and Yang's recent coalescent methods. The confidence limits on tau decrease when the range over which ancestral population size theta is assumed to be distributed decreases and when tau increases; they generally exclude zero when tau/(4Ne) > 1. We also apply a maximum-likelihood method to several single and multilocus data sets. With multilocus data, the criterion for excluding tau = 0 is roughly that l tau/(4Ne) > 1, where l is the number of loci. Our analyses corroborate recent suggestions that increasing the number of loci is critical to decreasing the uncertainty in estimates of population divergence time. PMID- 11209765 TI - Fixation of new alleles and the extinction of small populations: drift load, beneficial alleles, and sexual selection. AB - With a small effective population size, random genetic drift is more important than selection in determining the fate of new alleles. Small populations therefore accumulate deleterious mutations. Left unchecked, the effect of these fixed alleles is to reduce the reproductive capacity of a species, eventually to the point of extinction. New beneficial mutations, if fixed by selection, can restore some of this lost fitness. This paper derives the overall change in fitness due to fixation of new deleterious and beneficial alleles, as a function of the distribution of effects of new mutations and the effective population size. There is a critical effective size below which a population will on average decline in fitness, but above which beneficial mutations allow the population to persist. With reasonable estimates of the relevant parameters, this critical effective size is likely to be a few hundred. Furthermore, sexual selection can act to reduce the fixation probability of deleterious new mutations and increase the probability of fixing new beneficial mutations. Sexual selection can therefore reduce the risk of extinction of small populations. PMID- 11209766 TI - Runaway sexual selection when female preferences are directly selected. AB - We introduce models for the runaway coevolution of female mating preferences and male display traits. The models generalize earlier results by allowing for direct natural selection on the preference, arbitrary forms of mate choice, and fairly general assumptions about the underlying genetics. Results show that a runaway is less likely when there is direct selection on the preference, but that it is still possible if there is a sufficiently large phenotypic correlation between the female's preference and the male's trait among mated pairs. Comparison of three preference functions introduced by Lande (1981) shows that open-ended preferences are particularly prone to a runaway, and that absolute preferences require very large differences between females in their preferences. We analyze the causes of the runaway seen in a model developed by Iwasa and Pomiankowski (1995). PMID- 11209767 TI - A deterministic genetic model for sympatric speciation by sexual selection. AB - A deterministic haploid genetic model confirms and explores in more detail the results of our previous individual-based simulation model for sympatric speciation by sexual selection. With the deterministic model, we are able to elucidate parameter dependence by phase plane analysis. We clarify how and why sympatric speciation by sexual selection can happen in a number of ways: (1) Female preferences for or against particular types of males have different effects. Whereas the former affects how readily speciation is invoked, the latter changes the stability of speciation equilibrium. (2) When there is no cost on male ornamentations, speciation is triggered regardless of initial haplotype frequencies if sufficient female preference is provided. (3) There exists a threshold for female initial frequencies for speciation to be invoked, but male initial frequencies have little effect. (4) A small cost on female mate choice does not cancel speciation, but when large, it greatly reduces the possibility of speciation. PMID- 11209768 TI - Gene interactions from maternal effects. AB - Theoretical analyses have demonstrated a potential role for epistasis in many of the most important processes in evolution. These analyses generally assume that an individual's genes map directly to its phenotype and epistasis results from interactions among loci that contribute to the same biochemical or developmental pathways (termed physiological, or within-genotype, epistasis). For many characters, particularly those expressed early in life, an individual's phenotype may also be affected by genes expressed by its parents. The presence of these parental effects allows for interactions between the genes present in the parental and offspring genomes. When the phenotypic effect of a locus in the offspring depends on the alleles possessed by its parents, genotype-by-genotype, or among-genotype, epistasis occurs. The among-genotype epistasis resulting from parental effects may contribute to ruggedness of adaptive landscapes because early mortality often accounts for much of the variance in fitness in populations. To demonstrate how parent-offspring interactions can result in among genotype epistasis, I use a two-locus model, with one maternal effect locus and one direct effect locus, each with two alleles. Dynamical equations are presented for the two-locus model and are directly contrasted with the dynamical equations derived for a model for physiological epistasis. The relationship between the evolutionary dynamics resulting from these two forms of epistasis is discussed. Three scenarios are presented to illustrate systems in which maternal-offspring, genotype-by-genotype epistasis may occur. The implications of maternal-offspring epistasis for quantitative-trait-loci studies are also discussed. PMID- 11209769 TI - The evolutionary dynamics of direct phenotypic overdominance: emergence possible, loss probable. AB - An evolutionary dynamical system with explicit diploid genetics is used to investigate the likelihood of observing phenotypically overdominant heterozygotes versus heterozygous phenotypes that are intermediate between the homozygotes. In this model, body size evolves in a population with discrete demographic episodes and with competition limiting reproduction. A genotype-phenotype map for body size is used that can generate the two qualitative types of dominance interactions (overdominance versus intermediate dominance). It is written as a single-locus model with one focal locus and parameters summarizing the effects of alleles at other loci. Two types of evolutionarily stable strategy (ESS; continuously stable strategy, CSS) occur. The ESS is generated either (1) by the population ecology; or (2) by a local maximum of the genotype-phenotype map. Overdominant heterozygotes are expected to arise if the population evolves toward the second type of ESS, where nearly maximum body sizes are found. When other loci with partially dominant inheritance also evolve, the location of the maximum in the genotype-phenotype map repeatedly changes. It is unlikely that an evolving population will track these changes; ESSs of the second type now are at best quasi-stationary states of the evolutionary dynamics. Considering the restrictions on its probability, a pattern of phenotypic overdominance is expected to be rare. PMID- 11209770 TI - Molecular evolution, adaptive radiation, and geographic diversification in the amphiatlantic family Rapateaceae: evidence from ndhF sequences and morphology. AB - Rapateaceae (16 genera, approximately 100 species) is largely restricted to the tepuis and sandplains of the Guayana Shield in northern South America, with Maschalocephalus endemic to West Africa. The family has undergone extensive radiation in flower form, leaf shape, habit, and habitat. To analyze the evolution of these distributions and traits, we derived a molecular phylogeny for representatives of 14 genera, based on sequence variation in the chloroplast encoded ndhF gene. The lowland subfamily Rapateoideae is paraphyletic and includes the largely montane subfamily Saxofridericioideae as a monophyletic subset. Overall, the morphological/anatomical data differ significantly from ndhF sequences in phylogenetic structure, but show a high degree of concordance with the molecular tree in three of four tribes. Branch lengths are consistent with the operation of a molecular clock. Maschalocephalus diverges only slightly from other Monotremae: it is the product of relatively recent, long-distance dispersal, not continental drift--only its habitat atop rifted, nutrient-poor sandstones is vicariant. The family appears to have originated approximately 65 Mya in inundated lowlands of the Guayana Shield, followed by: (1) wide geographic spread of lowland taxa along riverine corridors; (2) colonization of Amazonian white-sand savannas in the western Shield; (3) invasion of tepui habitats with frequent speciation, evolution of narrow endemism, and origin of hummingbird pollination in the western Shield; and (4) reinvasion of lowland white-sand savannas. The apparent timing of speciation in the Stegolepis alliance about 6-12 Mya occurred long after the tepuis began to be dissected from each other as the Atlantic rifted approximately 90 Mya. Given the narrow distributions of most montane taxa, this suggests that infrequent long-distance dispersal combined with vicariance accounts for speciation atop tepuis in the Stegolepis alliance. PMID- 11209771 TI - Plant genetics affects arthropod community richness and composition: evidence from a synthetic eucalypt hybrid population. AB - To examine how genetic variation in a plant population affects arthropod community richness and composition, we quantified the arthropod communities on a synthetic population of Eucalyptus amygdalina, E. risdonii, and their F1 and advanced-generation hybrids. Five major patterns emerged. First, the pure species and hybrid populations supported significantly different communities. Second, species richness was significantly greatest on hybrids (F1 > F2 > E. amygdalina > E. risdonii). These results are similar to those from a wild population of the same species and represent the first case in which both synthetic and wild population studies confirm a genetic component to community structure. Hybrids also acted as centers of biodiversity by accumulating both the common and specialist taxa of both parental species (100% in the wild and 80% in the synthetic population). Third, species richness was significantly greater on F1s than the single F2 family, suggesting that the increased insect abundance on hybrids may not be caused by the breakup of coadapted gene complexes. Fourth, specialist arthropod taxa were most likely to show a dominance response to F1 hybrids, whereas generalist taxa exhibited a susceptible response. Fifth, in an analysis of 31 leaf terpenoids that are thought to play a role in plant defense, hybrids were generally intermediate to the parental chemotypes. Within the single F2 family, we found significant associations between the communities of individual trees and five individual oil components, including oil yield, demonstrating that there is a genetic effect on plant defensive chemistry that, in turn, may affect community structure. These studies argue that hybridization has important community-level consequences and that the genetic variation present in hybrid zones can be used to explore the genetic-based mechanisms that structure communities. PMID- 11209772 TI - Costs of plasticity in foraging characteristics of the clonal plant Ranunculus reptans. AB - In clonal plants, evolution of plastic foraging by increased lengths of leaves and internodes under unfavourable conditions may be constrained by costs and limits of plasticity. We studied costs and limits of plasticity in foraging characteristics in 102 genotypes of the stoloniferous herb Ranunculus reptans. We grew three replicates of each genotype with and three without competition by the naturally co-occuring grass Agrostis stolonifera. We used regression and correlation analyses to investigate potential costs of plasticity in lengths of leaves and stolon internodes, developmental instability costs of these traits, and a developmental range limit of these traits. We used randomization procedures to control for spurious correlations between parameters calculated from the same data. Under competition the number of rosettes, rooted rosettes, and flowers was 58%, 40%, and 61% lower, respectively, than in the absence of competition. Under competition lengths of leaves and stolon internodes were 14% and 6% smaller, respectively, than in the absence of competition. We detected significant costs of plasticity in stolon internode length in the presence of competition when fitness was measured in terms of the number of rosettes and the number of flowers (selection gradients against plasticity were 0.250 and 0.214, respectively). Within-environment variation (SD) in both foraging traits was not positively correlated with the corresponding plasticity, which indicates that there were no developmental instability costs. More plastic genotypes did not have less extreme trait values than less plastic genotypes for both foraging traits, which indicates that there was no developmental range limit. We conclude that in R. reptans costs of plasticity more strongly constrain evolution of foraging in the horizontal plane (i.e., stolon internode length) than in the vertical plane (i.e., leaf length). PMID- 11209773 TI - Evidence of adaptive divergence in plasticity: density- and site-dependent selection on shade-avoidance responses in Impatiens capensis. AB - We investigated the conditions under which plastic responses to density are adaptive in natural populations of Impatiens capensis and determined whether plasticity has evolved differently in different selective environments. Previous studies showed that a population that evolved in a sunny site exhibited greater plasticity in response to density than did a population that evolved in a woodland site. Using replicate inbred lines in a reciprocal transplant that included a density manipulation, we asked whether such population differentiation was consistent with the hypothesis of adaptive divergence. We hypothesized that plasticity would be more strongly favored in the sunny site than in the woodland site; consequently, we predicted that selection would be more strongly density dependent in the sunny site, favoring the phenotype that was expressed at each density. Selection on internode length and flowering date was consistent with the hypothesis of adaptive divergence in plasticity. Few costs or benefits of plasticity were detected independently from the expressed phenotype, so plasticity was selected primarily through selection on the phenotype. Correlations between phenotypes and their plasticity varied with the environment and would cause indirect selection on plasticity to be environment dependent. We showed that an appropriate plastic response even to a rare environment can greatly increase genotypic fitness when that environment is favorable. Selection on the measured characters contributed to local adaptation and fully accounted for fitness differences between populations in all treatments except the woodland site at natural density. PMID- 11209774 TI - Density dependence and population differentiation of genetic architecture in Impatiens capensis in natural environments. AB - We identified environment-dependent constraints on the evolution of plasticity to density under natural conditions in two natural populations of Impatiens capensis. We also examined the expression of population divergence in genetic variance-covariance matrices in these natural environments. Inbred lines, originally collected from a sunny site with high seedling densities and a woodland site with low seedling densities, were planted in both original sites at natural high densities and at low density. Morphological and life-history characters were measured. More genetic variation for plastic responses to density was expressed in the sun site than in the woodland site, so the evolutionary potential of plasticity was greater in the sun site. Strong genetic correlations between the same character expressed at different densities and correlations among different characters could constrain the evolution of plasticity in both sites. Genetically based trade-offs in meristem allocation to vegetative growth and reproduction were apparent only in the high-resource environment with no overhead canopy and no intraspecific competition. Therefore, genetic constraints on the evolution of plasticity depended on the site and density in which plants were grown, and correlated responses to selection on plastic characters are also expected to differ between sites and densities. Population differentiation in genetic variance-covariance matrices was detected, but matrix structural differences, as opposed to proportional differences, were detected between populations only in the sun site at natural high density. Thus, population divergence in genetic architecture can occur rapidly and on a fine spatial scale, but the expression of such divergence may depend on the environment. PMID- 11209775 TI - Plasticity to light cues and resources in Arabidopsis thaliana: testing for adaptive value and costs. AB - Plants shaded by neighbors or overhead foliage experience both a reduction in the ratio of red to far red light (R:FR), a specific cue perceived by phytochrome, and reduced photosynthetically active radiation (PAR), an essential resource. We tested the adaptive value of plasticity to crowding and to the cue and resource components of foliage shade in the annual plant Arabidopsis thaliana by exposing 36 inbred families from four natural populations to four experimental treatments: (1) high density, full sun; (2) low density, full sun; (3) low density, neutral shade; and (4) low density, low R:FR-simulated foliage shade. Genotypic selection analysis within each treatment revealed strong environmental differences in selection on plastic life-history traits. We used specific contrasts to measure plasticity to density and foliage shade, to partition responses to foliage shade into phytochrome-mediated responses to the R:FR cue and responses to PAR, and to test whether plasticity was adaptive (i.e., in the same direction as selection in each environment). Contrary to expectation, we found no evidence for adaptive plasticity to density. However, we observed both adaptive and maladaptive responses to foliage shade. In general, phytochrome-mediated plasticity to the R:FR cue of foliage shade was adaptive and counteracted maladaptive growth responses to reduced PAR. These results support the prediction that active developmental responses to environmental cues are more likely to be adaptive than are passive resource-mediated responses. Multiple regression analysis detected a few costs of adaptive plasticity and adaptive homeostasis, but such costs were infrequent and their expression depended on the environment. Thus, costs of plasticity may occasionally constrain the evolution of adaptive responses to foliage shade in Arabidopsis, but this constraint may differ among environments and is far from ubiquitous. PMID- 11209776 TI - Evolution of reproductive strategies in the sexually deceptive orchid Ophrys sphegodes: how does flower-specific variation of odor signals influence reproductive success? AB - The orchid Ophrys sphegodes Miller is pollinated by sexually excited males of the solitary bee Andrena nigroaenea, which are lured to the flowers by visual cues and volatile semiochemicals. In O. sphegodes, visits by pollinators are rare. Because of this low frequency of pollination, one would expect the evolution of strategies that increase the chance that males will visit more than one flower on the same plant; this would increase the number of pollination events on a plant and therefore the number of seeds produced. Using gas chromatography-mass spectrometry (GC-MS) analyses, we identified more than 100 compounds in the odor bouquets of labellum extracts from O. sphegodes; 24 compounds were found to be biologically active in male olfactory receptors based on gas chromatography with electroantennographic detection (GC-EAD). Gas chromatography (GC) analyses of odors from individual flowers showed less intraspecific variation in the odor bouquets of the biologically active compounds as compared to nonactive compounds. This can be explained by a higher selective pressure on the pollinator-attracting communication signal. Furthermore, we found a characteristic variation in the GC EAD active esters and aldehydes among flowers of different stem positions within an inflorescence and in the n-alkanes and n-alkenes among plants from different populations. In our behavioral field tests, we showed that male bees learn the odor bouquets of individual flowers during mating attempts and recognize them in later encounters. Bees thereby avoid trying to mate with flowers they have visited previously, but do not avoid other flowers either of a different or the same plant. By varying the relative proportions of saturated esters and aldehydes between flowers of different stem positions, we demonstrated that a plant may take advantage of the learning abilities of the pollinators and influence flower visitation behavior. Sixty-seven percent of the males that visited one flower in an inflorescence returned to visit a second flower of the same inflorescence. However, geitonogamy is prevented and the likelihood of cross-fertilization is enhanced by the time required for the pollinium deposited on the pollinator to complete its bending movement, which is necessary for pollination to occur. Cross fertilization is furthermore enhanced by the high degree of odor variation between plants. This variation minimizes learned avoidance of the flowers and increases the likelihood that a given pollinator would visit several to many different plants within a population. PMID- 11209777 TI - Formulation and estimation of the effective size of stage-structured populations in Fritillaria camtschatcensis, a perennial herb with a complex life history. AB - The effective population size (Ne) is formulated based on a stage-structured population model and is estimated for two populations of Fritillaria camtschatcensis (L.) Ker-Gawl. (Liliaceae), a perennial, mainly clonally reproducing herb. Plants in these populations change life-history stages year by year, either upward or downward across three unambiguously identifiable stages: one-leaf, nonflowering; multileaf nonflowering; and multileaf, flowering stages. Plants of all stages produce clonal progeny (bulblets) each year, and death of plants occurs only in the first stage. The populations are nearly at equilibrium in both population size and stage structure. Ne is estimated to be 20-30% of the census population size (N), leading to the prediction that a population size of about 20,000 or more will be needed to conserve the normal level of the gene diversity (Ne > or = 5000). With the current demographic pattern of this species, accelerated growth of the first-stage plants with reduced survival of the second- and third-stage plants will increase both the annual (Ny/N) and generation time (Ne/N) effective sizes of population. PMID- 11209778 TI - Global phylogeography of a cryptic copepod species complex and reproductive isolation between genetically proximate "populations". AB - The copepod Eurytemora affinis has a broad geographic range within the Northern Hemisphere, inhabiting coastal regions of North America, Asia, and Europe. A phylogenetic approach was used to determine levels of genetic differentiation among populations of this species, and interpopulation crosses were performed to determine reproductive compatibility. DNA sequences from two mitochondrial genes, large subunit (16S) rRNA (450 bp) and cytochrome oxidase I (COI, 652 bp), were obtained from 38 populations spanning most of the species range and from two congeneric species, E. americana and E. herdmani. Phylogenetic analysis revealed a polytomy of highly divergent clades with maximum sequence divergences of 10% in 16S rRNA and 19% in COI. A power test (difference of a proportion) revealed that amount of sequence data collected was sufficient for resolving speciation events occurring at intervals greater than 300,000 years, but insufficient for determining whether speciation events were approximately simultaneous. Geographic and genetic distances were not correlated (Mantel's test; r = 0.023, P = 0.25), suggesting that populations had not differentiated through gradual isolation by distance. At finer spatial scales, there was almost no sharing of mtDNA haplotypes among proximate populations, indicating little genetic exchange even between nearby sites. Interpopulation crosses demonstrated reproductive incompatibility among genetically distinct populations, including those that were sympatric. Most notably, two geographically distant (4000 km) but genetically proximate (0.96% 16S, 0.15% COI) populations exhibited asymmetric reproductive isolation at the F2 generation. Large genetic divergences and reproductive isolation indicate that the morphologically conservative E. affinis constitutes a sibling species complex. Reproductive isolation between genetically proximate populations underscores the importance of using multiple measures to examine patterns of speciation. PMID- 11209779 TI - Mechanisms of conspecific sperm precedence in Drosophila. AB - The postmating, prezygotic isolating mechanism known as conspecific sperm precedence (CSP) may play an important role in speciation, and understanding the mechanism of CSP is important in reconstructing its evolution. When a Drosophila simulans female mates with both a D. simulans male and a D. mauritiana male, the vast majority of her progeny are fathered by D. simulans, regardless of the order of mating. The dearth of hybrid progeny does not result from inviability of eggs fertilized by heterospecific sperm or from the relative inviability of heterospecific larvae. Instead, CSP apparently results from a prefertilization obstacle to heterospecific sperm. We identified two independent barriers to heterospecific fertilization, sperm displacement and incapacitation, whose action depends on the order of mating. When a D. simulans female mates first with a conspecific male, the seminal fluid from this mating incapacitates heterospecific sperm transferred two days later. This sperm incapacitation occurs with no change in the retention of stored sperm over time, but does not occur when the conspecific mating lasts for only 5 min. When the order of matings is reversed, the seminal fluid from the second mating physically displaces heterospecific sperm from storage, even if the conspecific copulation lasts only 5 min. Conspecific sperm are not susceptible to displacement by a second conspecific copulation, but are susceptible to interference by heterospecific sperm if the conspecific copulation is interrupted after 12 min. Curing the D. mauritiana males of their infection with the endosymbiont Wolbachia had no effect on CSP. Sperm displacement and incapacitation involve the same basic mechanisms seen in second-male sperm precedence within species, supporting the hypothesis that CSP is an evolutionary by-product of adaptations affecting sperm competition within species. PMID- 11209780 TI - Reproductive costs of heat shock protein in transgenic Drosophila melanogaster. AB - Senescence may evolve when genes have antagonistic effects between early reproduction and later age-specific mortality. Although widely consistent with data of quantitative genetics, this model has yet to be validated with the identification of a specific locus presenting such trade-offs. The molecular chaperone hsp70 may be a candidate for such a gene. Heat induced expression of the Hsp70 protein in adults decreases rates of age-specific mortality during normal aging, while maternally experienced heat shock depresses the production of mature progeny. Here we show that maternal heat shock reduces the proportion of egg hatch but not the viability of successfully hatched offspring. To assess whether heat induced maternal expression of hsp70 causes reduced egg hatch, we measured the proportion of eggs that hatch from females engineered to overexpress hsp70 transgenes. We used the same transgenic strains that extend longevity upon hsp70 expression and found that Hsp70 is sufficient to suppress egg hatch. The proportion of egg hatch as a function of hsp70 expression was not reduced in the first eggs laid after maternal heat shock, but appears in later laid eggs, which were at preoogenic and early vitellogenic stages during the maternal expression of hsp70. The contervailing effects of hsp70 upon fecundity and subsequent age specific mortality exemplify antagonistic pleiotropy, and this trade-off could contribute to the evolution of Drosophila senescence. PMID- 11209781 TI - Evolution of abdominal pigmentation differences across species in the Drosophila dunni subgroup. AB - The Drosophila dunni subgroup displays a nearly perfect latitudinal cline in abdominal pigmentation that likely resulted from selective forces acting in the habitat of each species during speciation. Here we characterize the nature of this clinal variation by developing a quantitative measure to assess variation in abdominal pigmentation within and between the D. dunni subgroup species. Using discriminant analysis, we confirm the existence of a cline and find that our quantitative measure of pigmentation distinguishes each of the species with singular efficacy. We then combine our quantitative phenotypic analysis of pigmentation with the phylogeny of the D. dunni subgroup species and map the species relationships into the three-dimensional morphological space defined by our pigmentation measures. In this manner, we can visualize how the species have traversed the morphological pigmentation space during the course of speciation. Our analysis reveals that natural selection has caused overall intensity of pigmentation among the northernmost species of the cline to converge. Along with this convergence in phenotype has been a relaxation in expression of sexual dimorphism in these species, indicating a possible shift in the relative intensity of natural and sexual selection. Our analysis indicates an accelerated rate of change in pigmentation for the darkest species in addition to this species evolving a novel abdominal pigmentation trait. PMID- 11209782 TI - Genetic and developmental analysis of abdominal pigmentation differences across species in the Drosophila dunni subgroup. AB - Abdominal pigmentation pattern varies dramatically among the species of the Drosophila dunni subgroup across the islands of the Caribbean. Previously, we developed a quantitative measure of abdominal pigmentation to assess phenotypic variation within and between species of this group. In this paper, we use this quantitative measure in an interspecific genetic analysis to decipher the underlying genetic basis of pigmentation differences between one of the lightest and the darkest species in the group. Our analysis shows that pigmentation expression in different areas of the abdomen is under separate genetic control. For these different abdominal regions, we detected a wide range of genetic effects, including X-linked, autosomal additive, near single-gene dominant, and sex-specific effects. Combining these genetic results with our earlier phenotypic and phylogenetic analyses, we present a simple conceptual model to explain how change in the control of expression of pigmentation has evolved throughout the D. dunni subgroup. PMID- 11209783 TI - Predisposed to adapt? Clade-level differences in characters affecting swimming performance in damselflies. AB - Previous studies have shown that two or three lineages of Enallagma damselflies, which historically co-existed with fish, recently invaded and adapted to living with large dragonfly predators in fishless waters. In adapting to live with these new predators, lineages shifted behaviorally to using swimming as an evasive tactic against attacking predators, evolved morphological features that made them faster swimmers, and evolved biochemical features to increase refueling strenuous activities like swimming. However, these habitat shifts have occurred in only one of the two primary clades within the genus in North America. Here, I show that clade-level differences exist among species in the ancestral, fish-lake habitat that should make habitat shifts easier to accomplish in the clade in which they have occurred. Specifically, fish-lake species in the clade in which habitat shifts occurred have much higher propensities to swim in the laboratory, swim faster when they do swim, and have higher mass-specific activities for arginine kinase than do species in the other primary clade, in which no extant species are found in fishless waters. These results are discussed in the context of the dynamics of founder events and the potential implications for community structure. PMID- 11209784 TI - Interpreting colonization of the Calathus (Coleoptera: Carabidae) on the Canary Islands and Madeira through the application of the parametric bootstrap. AB - The Canary Islands have proven to be an interesting archipelago for the phylogeographic study of colonization and diversification with a number of recent studies reporting evolutionary patterns and processes across a diversity of floral and faunal groups. The Canary Islands differ from the Hawaiian and Galapagos Islands by their close proximity to a continental land mass, being 110 km from the northwestern coast of Africa. This close proximity to a continent obviously increases the potential for colonization, and it can be expected that at the level of the genus some groups will be the result of more than one colonization. In this study we investigate the phylogeography of a group of carabid beetles from the genus Calathus on the Canary Islands and Madeira, located 450 km to the north of the Canaries and 650 km from the continent. The Calathus are well represented on these islands with a total of 29 species, and on the continent there are many more. Mitochondrial cytochrome oxidase I and II sequence data has been used to identify the phylogenetic relationships among the island species and a selection of continental species. Specific hypotheses of monophyly for the island fauna are tested with parametric bootstrap analysis. Data suggest that the Canary Islands have been colonized three times and Madeira twice. Four of these colonizations are of continental origin, but it is possible that one Madeiran clade may be monophyletic with a Canarian clade. The Calathus faunas of Tenerife and Madeira are recent in origin, similar to patterns previously reported for La Gomera, El Hierro, and Gran Canaria. PMID- 11209785 TI - An experimental study of intraspecific variation, developmental timing, and heterochrony in fishes. AB - Heterochrony is widely regarded as an important evolutionary mechanism, one that may underlie most, if not all, morphological evolution, yet relatively few studies have examined variation in the sequence of development. Even fewer studies have been designed so that intraspecific variation in the relative sequence of developmental events can be assessed, although this variation must be the basis for evolutionary change. Intraspecific variation in developmental ossification sequences was documented from the zebrafish (Danio rerio) by Cubbage and Mabee (1996) and from the Siamese fighting fish (Betta splendens) by Mabee and Trendler (1996), but a quantitative analysis of the patterns within this variation was not made. Here, we quantify the effect of rearing temperature on the sequence of ossification and characterize the levels and patterns of intraspecific variation in these fishes. For Danio, there were no temperature effects on the sequence of bone development across the cranium, cranial region development, cartilage versus dermal bones, or lateral line bone versus nonassociated bones. Likewise the level of variation in relative sequence (position) of ossification was low, about two ranks, across temperatures. At higher temperatures, we found higher levels of variation in iterated cranial bones and less in bones forming early in the sequence. No temperature effects on variation were found among regions, between lateral line-associated bones and nonassociated bones, between median and paired bones, or across the entire sequence, indicating concordant variability among the three temperatures. Individual bones with the highest levels of variability were not consistent among temperatures. Baseline patterns of intraspecific variation in Danio were compared to those of Betta. For both species, the level of intraspecific variation in sequence position was low and the variability of cranial bones was concordant. Individual bones with the highest levels of variability were not consistent between species. In both species, variation was widespread (distributed evenly across the sequence). We used comparisons (among regions, between dermal and cartilage bones, between lateral line-associated and other bones, between median and paired bones, between iterated and noniterated bones, between feeding associated bones and others) to see which subsets were most variable and thus potentially useful in predicting high levels of evolutionary change. The only subset of bones that was significantly more variable than others was cartilage bones. If interspecific patterns are parallel to these intraspecific differences, cartilage bones would be expected to show higher levels of heterochrony. Although concordance across the cranial ossification sequence and among regions in Danio, Betta, and two other teleosts, Oryzias and Barbus, suggests an evolutionarily conserved pattern of ossification, identity in sequence position across taxa was not observed for any bone. Thus, variation existed in sequence position across temperatures and species. Intraspecific variation of this sort may influence the morphological outcome and evolutionary trajectories of species. PMID- 11209786 TI - Mitochondrial DNA phylogeography of the polytypic North American rat snake (Elaphe obsoleta): a critique of the subspecies concept. AB - Subspecies have been considered artificial subdivisions of species, pattern classes, or incipient species. However, with more data and modern phylogenetic techniques, some subspecies may be found to represent true species. Mitochondrial DNA analysis of the polytypic snake, Elaphe obsoleta, yields well-supported clades that do not conform to any of the currently accepted subspecies. Complete nucleotide sequences of the cytochrome b gene and the mitochondrial control region produced robust maximum-parsimony and maximum-likelihood trees that do not differ statistically. Both trees were significantly shorter than a most parsimonious tree in which each subspecies was constrained to be monophyletic. Thus, the subspecies of E. obsoleta do not represent distinct genetic lineages. Instead, the evidence points to three well-supported mitochondrial DNA clades confined to particular geographic areas in the eastern United States. This research underscores the potential problems of recognizing subspecies based on one or a few characters. PMID- 11209787 TI - Reconstructing plumage evolution in orioles (Icterus): repeated convergence and reversal in patterns. AB - Several empirical studies suggest that sexually selected characters, including bird plumage, may evolve rapidly and show high levels of convergence and other forms of homoplasy. However, the processes that might generate such convergence have not been explored theoretically. Furthermore, no studies have rigorously addressed this issue using a robust phylogeny and a large number of signal characters. We scored the appearance of 44 adult male plumage characters that varied across New World orioles (Icterus). We mapped the plumage characters onto a molecular phylogeny based on two mitochondrial genes. Reconstructing the evolution of these characters revealed evidence of convergence or reversal in 42 of the 44 plumage characters. No plumage character states are restricted to any groups of species higher than superspecies in the oriole phylogeny. The high frequency of convergence and reversal is reflected in the low overall retention index (RI = 0.66) and the low overall consistency index (CI = 0.28). We found similar results when we mapped plumage changes onto a total evidence tree. Our findings reveal that plumage patterns and colors are highly labile between species of orioles, but highly conserved within the oriole genus. Furthermore, there are at least two overall plumage types that have convergently evolved repeatedly in the three oriole clades. This overall convergence leads to significant conflict between the molecular and plumage data. It is not clear what evolutionary processes lead to this homoplasy in individual characters or convergence in overall pattern. However, evolutionary constraints such as developmental limitations and genetic correlations between characters are likely to play a role. Our results are consistent with the belief that avian plumage and other sexually selected characters may evolve rapidly and may exhibit high homoplasy. The overall convergence in oriole plumage patterns is an interesting evolutionary phenomenon, but it cautions against heavy reliance on plumage characters for constructing phylogenies. PMID- 11209788 TI - The evolution of sexual size dimorphism in the house finch. II. Population divergence in relation to local selection. AB - Recent colonization of ecologically distinct areas in North America by the house finch (Carpodacus mexicanus) was accompanied by strong population divergence in sexual size dimorphism. Here we examined whether this divergence was produced by population differences in local selection pressures acting on each sex. In a long term study of recently established populations in Alabama, Michigan, and Montana, we examined three selection episodes for each sex: selection for pairing success, overwinter survival, and within-season fecundity. Populations varied in intensity of these selection episodes, the contribution of each episode to the net selection, and in the targets of selection. Direction and intensity of selection strongly differed between sexes, and different selection episodes often favored opposite changes in morphological traits. In each population, current net selection for sexual dimorphism was highly concordant with observed sexual dimorphism--in each population, selection for dimorphism was the strongest on the most dimorphic traits. Strong directional selection on sexually dimorphic traits, and similar intensities of selection in both sexes, suggest that in each of the recently established populations, both males and females are far from their local fitness optimum, and that sexual dimorphism has arisen from adaptive responses in both sexes. Population differences in patterns of selection on dimorphism, combined with both low levels of ontogenetic integration in heritable sexually dimorphic traits and sexual dimorphism in growth patterns, may account for the close correspondence between dimorphism in selection and observed dimorphism in morphology across house finch populations. PMID- 11209789 TI - Major histocompatibility complex variation in the Arabian oryx. AB - In the 1960s, the Arabian oryx was one of the most endangered species in the world, extinct in the wild and surviving in only a few captive herds. The present day population of over 2000 descends from a small number of founders and may have restricted genetic variation for important adaptive genes. We have examined the amount of genetic variation for a class II gene in the major histocompatibility complex thought to be the most important genetic basis for pathogen resistance in vertebrates. We found three very divergent alleles, which on average, differed by 24 nucleotides and 15 amino acids in the 236-bp fragment we examined. Using single-strand conformation polymorphism, we found that in a sample of 57 animals, the alleles were in Hardy-Weinberg proportions, although one allele was found only in four heterozygous individuals. The average heterozygosity for the 22 amino acid positions involved in antigen binding was 0.165, three times as high as that for the 56 amino acids not involved with antigen binding. Because the three alleles have such divergent sequences, it is likely that they may recognize peptides from quite different pathogens. As a result, maintenance of these variants should be considered as a goal in the captive breeding program of the Arabian oryx. PMID- 11209790 TI - Selection on age at reproduction in Drosophila melanogaster: female mating frequency as a correlated response. AB - We examined the effect of selection for age at reproduction on female mating frequency and fertility in female Drosophila melanogaster. Selection for increased age at reproduction (and hence increased lifespan) resulted in higher late life female mating frequencies, while females selected for younger ages at reproduction showed increased early life mating frequencies. These results indicate that the response to selection on age at reproduction has involved changes in the scheduling of female reproductive behavior. PMID- 11209791 TI - Molecular evidence for selection on female color polymorphism in the damselfly Ischnura graellsii. AB - The significance of female color polymorphism in Odonata remains controversial despite many field studies. The importance of random factors (founder effects, genetic drift and migration) versus selective forces for the maintenance of this polymorphism is still discussed. In this study, we specifically test whether the female color polymorphism of Ischnura graellsii (Odonata, Coenagrionidae) is under selection in the wild. We compared the degree of genetic differentiation based on RAPD markers (assumed to be neutral) with the degree of differentiation based on color alleles. Weir and Cockerham's theta values showed a significant degree of population differentiation for both sets of loci (RAPD and color alleles) but the estimated degree of population differentiation (theta) was significantly greater for the set of RAPD loci. This result shows that some sort of selection contributes to the maintenance of similar color morph frequencies across the studied populations. Our results combined with those of previous field studies suggest that at least in some I. graellsii populations, density-dependent mechanisms might help to prevent the loss of this polymorphism but cannot explain the similarity in morph frequencies among populations. PMID- 11209792 TI - Copulating with multiple mates enhances female fecundity but not egg-to-adult survival in the bruchid beetle Callosobruchus maculatus. AB - Postcopulatory sexual selection theory has come a long way since the evolutionary implications of sperm competition were first spelled out by Parker (1970). However, one of the most enduring questions remains: why do females copulate with multiple males? Here we show that females copulating with multiple males lay more eggs than those copulating repeatedly with the same male. We also show egg-to adult survival to be more variable when females copulate multiply with different males and less variable when they copulate multiply with the same male. This supports the notion that egg-to-adult survival may depend on the genetic compatibility of males and females. However, pre-adult survival was highest when females copulated repeatedly with the same male rather than with different males. Thus, it would appear that polyandry in this species does not function to reduce the risk of embryo failure resulting from fertilization by genetically incompatible sperm. PMID- 11209793 TI - Little evidence for sympatric speciation in island birds. AB - It has been suggested that the presence of sister species in small circumscribed areas, such as isolated lakes or islands, might imply that these species originated sympatrically. To investigate this possibility in birds, we searched for endemic, congeneric species on isolated islands in the ocean. Among 46 islands and small archipelagos chosen because they contain at least one species of endemic land bird, we identified seven pairs of endemic congeners (excluding flightless rails). Of these seven, only four pairs are potentially sister species and thus possible candidates for sympatric speciation. However, three of these four pairs have always been considered the results of double invasion from a mainland source (in two of these cases, molecular-phylogenetic work has either confirmed a double invasion or is ambiguous). The one remaining pair may have speciated allopatrically on a small archipelago. Additional phylogenetic studies are required to understand these cases, and our results should also be considered in light of the large number of island-bird extinctions in historic time. We conclude that, at present, there is little evidence for sympatric speciation in island birds. PMID- 11209794 TI - Species recognition as a possible function for variations in position and shape of the sexually dimorphic tusks of Mesoplodon whales. AB - Beaked whales of the genus Mesoplodon are characterized by the presence of a single pair of sexually dimorphic tusks. Variation in the position and shape of these tusks was examined in four sympatric species and was found to be consistent with the hypothesis that these differences may have evolved to aid species recognition between sympatric and otherwise morphologically similar species of this genus. PMID- 11209795 TI - Gene flow between Drosophila pseudoobscura and D. persimilis. PMID- 11209796 TI - The road not taken. AB - The annual Janet Doe Lecture was established in 1966 to honor Janet Doe, emerita librarian of the New York Academy of Medicine. The lecture focuses on either the history or philosophy of health sciences librarianship. This lecture addresses three fundamental values of the field, highlighting basic beliefs of the profession that are at risk: privacy, intellectual property rights, and access to quality information. It calls upon readers to make the everyday choices required to keep the value system of health sciences librarianship in place. Robert Frost's poignant poem "The Road Not Taken" provides the metaphor for examining choices in an information economy. PMID- 11209797 TI - Using a journal availability study to improve access. AB - PURPOSE: Identify journal collection access and use factors. SETTING AND SUBJECTS: University of North Carolina at Chapel Hill's Health Sciences Library patrons. METHODOLOGY: Survey forms and user interactions were monitored once a week for twelve weeks during the fall 1997 semester. The project was based on a 1989 New Mexico State University study and used Kantor's Branching Analysis to measure responses. RESULT: 80% of reported sought journal articles were found successfully. Along with journal usage data, the library obtained demographic and behavioral information. DISCUSSION AND CONCLUSIONS: Journals are the library's most used resource and, even as more electronic journals are offered, print journals continue to make up the majority of the collection. Several factors highlighted the need to study journal availability. User groups indicated that finding journals was problematic, and internal statistics showed people requesting interlibrary loans for owned items. The study looked at success rates, time, and ease of finding journals. A variety of reasons contributed to not finding journals. While overall user reports indicated relatively high success rate and satisfaction, there were problems to be addressed. As the library proceeds in redesigning both the physical space and electronic presence, the collected data have provided valuable direction. PMID- 11209798 TI - Online tables of contents for books: effect on usage. AB - OBJECTIVES: To explore whether the presence of online tables of contents (TOC) in an online catalog affects circulation (checkouts and inhouse usage). Two major questions were posed: (1) did the presence of online tables of contents for books increase use, and, (2) if it did, what factors might cause the increase? METHOD: A randomized and stratified design was used in tracking usage of 3,957 book titles that were previously divided into two groups: one with TOC and one without TOC. Stratification was done for year of imprint, location, subject, previous use, circulating or non-circulating status, and presence of TOC. The use was tracked by the online catalog statistics in the InnoPac online catalog for fourteen months. RESULTS: The study found that tables of contents do increase usage. It also showed a correlation in the size of the effect based on the currency of the titles. In general, even after adjusting for all of the variables (publication date, location, circulation status, subject, and previous use), the odds of a title being used increased by 45% if the titles had online tables of contents, a statistically significant impact at the 0.05 level. CONCLUSIONS: This case-control study presents new information about the impact on circulation and inhouse use when tables of contents for books are added to the online catalog record. The study helps to establish the positive role of tables of contents in online catalogs. The research establishes TOC as a major parameter that can be successfully studied using quantitative methods. The study also provides information professionals with some guidance on when enhancement of TOC is likely to be most effective in increasing the use of existing collections. PMID- 11209800 TI - Republican Scientific-Medical Library, The Republic of Armenia: progress and programs. AB - In 1990, the Republican Scientific-Medical Library (RSML) of the Ministry of Health of Armenia in collaboration with the Fund for Armenian Relief created a vision of a national library network supported by information technology. This vision incorporated four goals: (1) to develop a national resource collection of biomedical literature accessible to all health professionals, (2) to develop a national network for access to bibliographic information, (3) to develop a systematic mechanism for sharing resources, and (4) to develop a national network of health sciences libraries. During the last decade, the RSML has achieved significant progress toward all four goals and has realized its vision of becoming a fully functional national library. The RSML now provides access to the literature of the health sciences including access to the Armenian medical literature, provides education and training to health professionals and health sciences librarians, and manages a national network of libraries of the major health care institutions in Armenia. The RSML is now able to provide rapid access to the biomedical literature and train health professionals and health sciences librarians in Armenia in information system use. This paper describes the evolution of the RSML and how it was accomplished. PMID- 11209799 TI - A rural virtual health sciences library project: research findings with implications for next generation library services. AB - PURPOSE: The Shared Hospital Electronic Library of Southern Indiana (SHELSI) research project was designed to determine whether access to a virtual health sciences library and training in its use would support medical decision making in rural southern Indiana and achieve the same level of impact seen by targeted information services provided by health sciences librarians in urban hospitals. METHODS: Based on the results of a needs assessment, a virtual medical library was created; various levels of training were provided. Virtual library users were asked to complete a Likert-type survey, which included questions on intent of use and impact of use. At the conclusion of the project period, structured interviews were conducted. RESULTS: Impact of the virtual health sciences library showed a strong correlation with the impact of information provided by health sciences librarians. Both interventions resulted in avoidance of adverse health events. Data collected from the structured interviews confirmed the perceived value of the virtual library. CONCLUSION: While librarians continue to hold a strong position in supporting information access for health care providers, their roles in the information age must begin to move away from providing information toward selecting and organizing knowledge resources and instruction in their use. PMID- 11209801 TI - Ethics and access to teaching materials in the medical library: the case of the Pernkopf atlas. AB - Conflicts can occur between the principle of freedom of information treasured by librarians and ethical standards of scientific research involving the propriety of using data derived from immoral or dishonorable experimentation. A prime example of this conflict was brought to the attention of the medical and library communities in 1995 when articles claiming that the subjects of the illustrations in the classic anatomy atlas, Eduard Pernkopf's Topographische Anatomie des Menschen, were victims of the Nazi holocaust. While few have disputed the accuracy, artistic, or educational value of the Pernkopf atlas, some have argued that the use of such subjects violates standards of medical ethics involving inhuman and degrading treatment of subjects or disrespect of a human corpse. Efforts were made to remove the book from medical libraries. In this article, the history of the Pernkopf atlas and the controversy surrounding it are reviewed. The results of a survey of academic medical libraries concerning their treatment of the Pernkopf atlas are reported, and the ethical implications of these issues as they affect the responsibilities of librarians is discussed. PMID- 11209802 TI - Non-librarian health professionals becoming librarians and information specialists: results of an Internet survey. AB - OBJECTIVES: To obtain basic information about non-librarian health professionals who become librarians and information specialists. METHODS: The survey was a Web based questionnaire. A non-random sample of persons was obtained by posting messages to several large Internet electronic discussion groups. Individuals who met the selection criteria and were willing to participate filled out a Web-based form designed using common gateway interface (CGI) programming. RESULTS: 118 forms were analyzed. Three subgroups of participants were identified and statistical comparisons among these groups were carried out for many of the quantitative questions. Information concerning reasons they left their original field; factors influencing their choice of the field of library and information science; reactions of family, friends, and colleagues; and interactions with patrons and other information about this group was obtained and summarized. A health sciences background was seen as helpful in the new career as information specialist. Most people were happy with their new profession despite negative reactions from colleagues, relatives, and, occasionally, patrons. Feelings of regret and abandonment of their patients were noted by some. Many persons did not know that peers had made similar career changes. CONCLUSIONS: A health sciences background imparts an expertise in both the vocabulary and subject matter of medicine that non-biomedical individuals would not ordinarily have. Although becoming a librarian may be perceived as a very positive career change for an individual, societal opinion and pressure can make such a career change difficult. Nevertheless, participants in this survey demonstrate a high level of satisfaction with their new careers and are quite happy with their work. PMID- 11209803 TI - Need a bloody nose be a nosebleed? or, lexical variants cause surprising results. PMID- 11209804 TI - Historically significant journal articles: their identification in older bound journal volumes designated for weeding and the creation of new access to these articles. PMID- 11209805 TI - What we don't know. PMID- 11209806 TI - The library as laboratory. PMID- 11209807 TI - Customizing for clients: developing a library liaison program from need to plan. AB - Building on the experiences of librarian representatives to curriculum committees in the colleges of dentistry, medicine, and nursing, the Health Science Center Libraries (HSCL) Strategic Plan recommended the formation of a Library Liaison Work Group to create a formal Library Liaison Program to serve the six Health Science Center (HSC) colleges and several affiliated centers and institutes. The work group's charge was to define the purpose and scope of the program, identify models of best practice, and recommend activities for liaisons. The work group gathered background information, performed an environmental scan, and developed a philosophy statement, a program of liaison activities focusing on seven primary areas, and a forum for liaison communication. Hallmarks of the plan included intensive subject specialization (beyond collection development), extensive communication with users, and personal information services. Specialization was expected to promote competence, communication, confidence, comfort, and customization. Development of the program required close coordination with other strategic plan implementation teams, including teams for collection development, education, and marketing. This paper discusses the HSCL's planning process and the resulting Library Liaison Program. Although focusing on an academic health center, the planning process and liaison model may be applied to any library serving diverse, subject-specific user populations. PMID- 11209808 TI - A tribute to knowledge. PMID- 11209809 TI - A small window on Janet Doe's life. PMID- 11209811 TI - Neoangiogenesis in squamous cell carcinoma of the larynx - biological and prognostic associations. AB - Tumor angiogenesis has been related to tumor growth and an increased probability of metastatic spread. Previous studies have led to conflicting views regarding the prognostic significance of angiogenesis in squamous cell carcinoma of the head and neck. To evaluate the role of tumor angiogenesis in the biology of squamous cell carcinoma of the larynx, we quantified the microvascular network in 59 primary laryngeal carcinomas and looked for an association with outcome. Microvessels were stained immunohistochemically using antibodies for factor VIII related antigen and the antibody JC70 (CD-31). In each case, microvessels were counted in three fields at x200 magnification, in areas of most intense neovascularization. We found a significantly higher number of microvessels in tumors showing deeper levels of invasion. PMID- 11209812 TI - Histopathological analyses of silent pituitary somatotroph adenomas using immunohistochemistry, in situ hybridization and confocal laser scanning microscopic observation. AB - To characterize the morphological and functional aspects of silent somatotroph adenomas with paradoxical responses of GH in TRH or GnRH provocation tests, which are considered to be a useful strategy for endocrinological identification of silent somatotroph adenomas, we examined three silent somatotroph adenomas histopathologically. The adenomas were investigated by immunohistochemistry, including the highly sensitive catalyzed signal amplification system, the non radioisotopic in situ hybridization method, and confocal laser scanning microscopy. GH production and GH-immunopositive secretory granules in the adenoma cells were demonstrated histopathologically, and the adenomas were interpreted as being densely granulated somatotroph adenomas. Endocrinological identification of silent somatotroph adenomas in combination with paradoxical responses of GH in TRH or GnRH provocation tests may elucidate the increasing number of silent somatotroph adenomas that have been regarded as mammotroph or clinically inactive adenomas. One should be aware of the differences between the previously reported silent somatotroph adenomas, most of which are sparsely granulated somatotroph adenomas, a somatotroph adenomas with paradoxical and the silent somatotroph adenomas, most of which are sparsely granulated somatotroph adenomas, and the silent somatotroph adenomas with paradoxical responses of GH in TRH or GnRH provocation tests, which are densely granulated somatotroph adenomas. PMID- 11209813 TI - Experimental induction of ring fibers in regenerating skeletal muscle. AB - Light microscopy and electron microscopy were used to study the formation of ring fibers induced experimentally in regenerating muscle subjected to tenotomy induced tension deficiency. Anterior tibial rat muscles were injured by intramuscular injection of mepivacain, tenotomized at varying stages of the regenerative process, and analyzed 30 days after sectioning the tendon. The combination of regeneration and tenotomy led to the appearance of ring fibers at different developmental stages. Ring fibers were not observed in regenerating control muscles and were scarce in tenotomized controls. Our results showed that the regenerative phase in which tension deficiency was established had a significant influence on the number of developing ring fibers; the number increased when tenotomy was performed during subsarcolemmic myofibrillogenesis in regenerating fibers. As a consequence, one might hypothesize that tension deficiency during muscle fiber repair plays a critical role in ring fiber formation. PMID- 11209814 TI - Cytological evaluation of the tissue-implant reaction associated with S/C and I/P implantation of ALCAP and HA bioceramics in vivo. AB - It is well documented that several ceramic materials are highly compatible and non-immunogenic with host tissues. Recent studies have demonstrated the need for further investigation of these devices in vivo to further elucidate the possible mechanisms involved in biocompatibility. The purpose of this investigation was to study the morphological characteristics of the fibrous tissue capsule resulting from the implantation of aluminum calcium phosphate (ALCAP) and hydroxyapetite (HA) bioceramics. Implants of ALCAP and HA were implanted into 10 adult male rats subcutaneously (S/C) and intraperitoneally (I/P). At 90 days post-implantation, the animals were euthanized, and the ceramic devices, the fibrous tissue, and vital organs were harvested. Evaluation of routine stained sections (5 microm, hematoxylin & eosin) of the fibrous tissue capsule surrounding the HA and ALCAP ceramics revealed the following: 1) all the ceramic devices had fibrous connective tissue capsules of slightly varying degrees of thickness at the time of sacrifice, depending on the site of implantation and type of material, and 2) there were statistically significant differences (p < 0.05) in the numbers and types of cellular components with respect to implantation site. The number of macrophages, neutrophils, fibroblasts, degree of vascularity, and thickness of the fibrous tissue matrix was found to be statistically different between the S/C implanted ceramic groups. The number of macrophages, neutrophils, fibroblasts, and collagen content comparing the fibrous tissue surrounding the ALCAP and HA ceramics (I/P), was found to be statisically different. PMID- 11209815 TI - A case of esophageal sarcomatoid carcinoma with molecular evidence of a monoclonal origin. AB - A case of polypoid tumor of the esophagus consisting of a sarcomatous tumor partly covered with superficial squamous cell carcinoma is described. The sarcomatous component consisted of anaplastic spindle and pleomorphic tumor cells that mimicked malignant fibrous histiocytoma (MFH). Both the sarcomatous and carcinomatous components were positive for p53 immunohistochemically. Further molecular analysis revealed that the two components had the same somatic mutation in the p53 gene. These results suggest a monoclonal origin of this biphasic tumor. PMID- 11209816 TI - Absence of connections between spinal nerves and the spinal cord in a twin fetus: a very rare malformation occasionally evidenced at autopsy. AB - We describe a rare case of spinal cord malformation in a dichorionic diamniotic twin fetus aborted at 20 weeks' gestation due to acute chorioamnionitis with placental dysmaturity probably caused by a maternal viral infection. At autopsy, there were no connections between the spinal nerves and the spinal cord. The spinal cord lacked the posterior median fissure and gray matter; only a few neurons were present in the anterior and lateral gray columns. No chromosome anomalies were found. Although we cannot reconstruct the pathogenetic chain of events leading to this malformation, we believe that it is correlated with a maternal viral infection. We hypothesize that this viral infection altered the delicate balance between the factors inducing and those inhibiting fetal spinal neural differentiation. PMID- 11209817 TI - Aggressive fibromatosis of the larynx: report of a new case in an adult patient and review of the literature. AB - We describe a case of aggressive fibromatosis of the larynx occurring in a 75 year-old man. The lesion manifested with voice hoarseness and swallowing difficulty. A computerized tomographic scan of the neck revealed distortion of the glottic profile. A malignant tumor was suspected. Although a laryngoscopy driven biopsy was non-diagnostic, total laryngectomy was done, since the lesion was not deemed amenable to conservative therapy. Grossly, the glottic rim was infiltrated by a hard, grey-white tissue showing a tentacular outline. Tissue sections featured a moderately cellular lesion composed of spindle cells with bland, tapered nuclei, enmeshed in a variably collagenized ground substance. Delicate spindle cell fascicles surrounded the native submucosal seromucous glands and had invaded the thyroid cartilage and the thyroid gland as well. The spindle cells were immunopositive for actins and vimentin, and negative for keratins, epithelial membrane antigen, desmin, and S-100 protein. No further therapy was administered. Periodic follow-up visits were negative. The patient died 5 years after surgery of myocardial infarction with no clinical evidence of lesion recurrence. Based on the available literature, our data confirm that laryngeal fibromatosis in adult patients is a locally infiltrating and progressive disease. Total laryngectomy with clear margins is needed as to avoid the high risk of local recurrence. PMID- 11209818 TI - Intrahepatic cholangitis and arteritis after transcatheter arterial embolization in a patient with tumor-like lesion-associated autoimmune hepatitis. AB - Autoimmune hepatitis is a chronic liver disease characterized by immune-mediated, progressive hepatocellular damage, although the target autoantigen remains speculative. Intrahepatic biliary lesions are not a feature of this disease. We describe herein a female patient, 57 years, with autoimmune hepatitis who developed hepatic regenerative mass after acute exacerbation of hepatitis. This hepatic regenerative mass was clinically diagnosed as hepatocellular carcinoma and was surgically resected after transcatheter arterial embolization therapy. Widespread nonsuppurative destructive granulomatous cholangitis as well as necrotizing, granulomatous arteritis of the intrahepatic small arteries were found in the surgically resected hepatic regenerative mass. The bile duct lesions were histologically and immunohistochemically very similar to the granulomatous cholangitis of primary biliary cirrhosis. We would like to propose that these unusual lesions in the intrahepatic bile ducts and intrahepatic arteries represent a reaction of this patient to an anti-cancer drug included in chemoembolization. No such cases have been reported so far. PMID- 11209819 TI - The prognostic value of DNA ploidy in small renal cell carcinoma. AB - The objective was to study the prognostic value of Deoxyribonucleic Acid (DNA) ploidy status in small renal cell carcinomas (RCC). The nuclear DNA content of renal cell carcinoma tissues from patients who underwent radical or partial nephrectomy has been analyzed by flow cytometry. The results of the DNA ploidy have been correlated to the size of tumors and disease progression. Of the 50 patients with RCC studied, 8 (16%) progressed. Tumors with non-diploid DNA patterns were found in 24 (48%) of the 50 patients and in 4 of the 8 patients who progressed. Overall the median tumor size in our series was 50 mm. A tumor diameter of 50 mm or less was measured in 26 patients (group I) and above 50 mm in 24 (group II). Non-diploid DNA patterns were found in 11 (42.3%) and 13 (54.2%) patients in groups I and II, respectively. This difference between the groups was not significant. Only one patient in group I (3.8%) developed metastatic disease and died 72 months after the operation. In group II, 7 patients (29.2%) presented tumor progression and 5 died of metastatic disease. The survival probability in group I was 95% at 5 and 8 years (95% CI 70% to 99%) and for group II 94% at 5 years (95% CI 67%-99%) and 67% at 8 years (95% CI 39% 83%). DNA ploidy is an inaccurate predictor of tumor behavior in patients with RCC, even in small tumors. Tumor size is a more significant predictor of outcome. PMID- 11209820 TI - Widespread risks of dental fluorosis in cotton rats (Sigmodon hispidus) residing on petrochemical waste sites. AB - Fluoride has been identified as a ubiquitous contaminant of soils where petrochemical wastes have been disposed. The purpose of this study was to assess how widespread toxicity risks are to resident vertebrates from chronic exposure to fluoride in the soil of petrochemical-contaminated waste sites. In total, 573 wild cotton rats (Sigmodon hispidus) were examined. The rats that were seasonally collected from 12 contaminated and 12 ecologically matched reference sites across Oklahoma over a 3-yr period. The risks of cotton rats exposed to fluoride were analyzed by means of gross examination, histopathology, and scanning electron microscopy of rat incisors. Cotton rats from reference sites showed no pathologic changes in incisors (98%). In comparison, 46% of cotton rats from contaminated sites had various degrees of dental lesions. The prevalence and severity of dental lesions in cotton rats from contaminated sites were significantly influenced by season. There was a 45% increase in prevalence and a 65% increase in severity of dental lesions from summer to winter. This study demonstrated that cotton rats are very sensitive biomonitors for assessing toxicity risks from soils contaminated with fluoride and that such assessments should consider seasonal influences. PMID- 11209821 TI - Comparative effects of dieldrin on hepatic ploidy, cell proliferation, and apoptosis in rodent liver. AB - Dieldrin-induced hepatocarcinogenesis, which is seen only in the mouse, apparently occurs through a nongenotoxic mechanism. Previous studies have demonstrated that dieldrin induces hepatic DNA synthesis in mouse, but not rat liver. A number of nongenotoxic hepatocarcinogens have been shown to increase hepatocyte nuclear ploidy following acute and subchronic treatment in rodents, suggesting that an induction of hepatocyte DNA synthesis may occur without a concomitant increase in cell division. The current study examined the effects of dieldrin on changes in hepatocyte DNA synthesis, mitosis, apoptosis, and ploidy in mouse liver (the sensitive strain and target tissue for dieldrin-induced carcinogenicity) and the rat liver (an insensitive species). Male F344 rats and B6C3F1 mice were treated with 0, 1, 3, or 10 mg dieldrin/kg diet and were sampled after 7, 14, 28, or 90 d on diet. Liver from mice fed 10 mg dieldrin/kg diet exhibited significantly increased DNA synthesis and mitosis at 14, 28, or 90 d on diet. In rats, no increase in DNA synthesis or mitotic index was observed. The apoptotic index in liver of mice and rats did not change over the 90-d study period. Exposure of mice to only the highest dose of dieldrin produced a significant increase in octaploid (8N) hepatocytes and a decrease in diploid (2N) hepatocytes, which were restricted primarily to centrilobular hepatocytes, with the periportal region showing little or no change from control. No changes in hepatocyte nuclear ploidy were observed in the rat. This study demonstrates that exposure to high concentrations of dieldrin is accompanied by increased nuclear ploidy and mitosis in mouse, but not rat, liver. It is proposed that the observed increase in nuclear ploidy in the mouse may reflect an adaptive response to dieldrin exposure. PMID- 11209822 TI - Exposure of Inuit in Greenland to organochlorines through the marine diet. AB - High organochlorine concentrations have been found among the Inuit in eastern Canada and in Greenland. The present study was undertaken to assess the exposure to organochlorines in relation to age, sex, and diet in a general population sample of Inuit from Greenland. Survey data and plasma concentrations of 14 polychlorinated biphenyl (PCB) congeners and 16 pesticides, including 5 toxaphene congeners, were recorded in a random population survey of 408 adult indigenous Greenlanders. In a two-stage design, the survey response rate was 66%, and 90% of those randomly selected for blood testing participated. This was equivalent to an overall response rate of 59%. The median plasma concentration of the sum of PCB congeners was 13.3 microg/L; the lipid-adjusted value was 2109 microg/kg. The PCB concentration was twice as high as among the Inuit of Nunavik, Canada, 25 times higher than in a control group from southern Canada, and several times higher than the values found in European studies. Concentrations were similarly elevated for all PCB congeners and pesticides. The PCB congener pattern was similar to previous observations from the eastern Canadian Arctic and Greenland. Concentrations showed statistically significant positive associations with age, marine diet, and male sex in multiple linear regression analyses. The exceptionally high plasma concentrations of several organochlorines among the Inuit of Greenland are attributed to a lifelong high intake of seafood, in particular marine mammals. Concentrations of PCB adjusted for the consumption of marine food increased until approximately 40 yr of age, which is equivalent to the birth cohorts of the early 1950s. The age pattern indicates that bioaccumulation of PCB started in the 1950s, which is a likely date for the introduction of the compounds into the Arctic environment. PMID- 11209823 TI - Evaluation of myelotoxicity in cotton rats (Sigmodon hispidus) exposed to environmental contaminants. I. In vitro bone-marrow progenitor culture. AB - Bone marrow is extremely sensitive to toxicants, and in vitro culture of bone marrow progenitor cells has been shown to be a sensitive indicator of bone-marrow injury in laboratory rodents. The ability of a bone-marrow progenitor cell assay to detect myelotoxicity in a wild rodent model (cotton rat, Sigmodon hispidus) that inhabits many contaminated ecosystems in the southern United States was examined. Responsiveness of progenitor cells to recombinant murine granulocyte macrophage colony-stimulating factor (GM-CSF) and cotton rat lung-conditioned medium (LCM) was determined to optimize culture conditions for cotton rats. Myelotoxicity was induced in cotton rats by treating animals with either cyclophosphamide (8 or 80 mg/kg) or dexamethasone (500 microg/kg) over a 5-d period. Administration of a high dose of cyclophosphamide caused nearly total suppression of colony formation of granulocyte-macrophage progenitor cells (CFU GM). Marked histological changes in both the bone marrow and spleen were also observed in cotton rats treated with a high dose of cyclophosphamide. Although histological lesions were not apparent, the number of CFU-GM in the bone marrow of low-dose cyclophosphamide- and dexamethasone-treated cotton rats was significantly suppressed compared to controls. The number of CFU-GM was consistently higher using LCM than recombinant murine GM-CSF. This reproducible, quantitative, in vitro bone-marrow progenitor cell culture system was a sensitive indicator of myelotoxicity in wild cotton rats and should be useful for monitoring chronic exposures to low levels of environmental toxicants in wild rodent populations. PMID- 11209824 TI - Evaluation of myelotoxicity in cotton rats (Sigmodon hispidus) exposed to environmental contaminants. II. Myelotoxicity associated with petroleum industrial wastes. AB - Various chemical mixtures exist in soil contaminated with petrochemical wastes, yet no comprehensive assessment of their impact on terrestrial ecosystems has been conducted. The purpose of this study was to evaluate hematotoxicity risks to wild populations of cotton rats (Sigmodon hispidus) residing in habitats previously contaminated by petroleum industrial wastes. Resident cotton rats were monitored on nine contaminated sites and nine ecologically matched reference sites in Oklahoma. The possible toxicological interactions of petrochemical wastes on bone marrow was investigated by using the assay of colony formation of granulocyte-macrophage progenitor cells. There was a consistent significant 21 to 39% decrease in the number of colony-forming units of granulocyte-macrophage (CFU GM) in cotton rats from petrochemical-contaminated sites compared to matched reference sites, with no marked changes in hematological or histopathological parameters. These results suggest that bone-marrow progenitor cell culture is a sensitive indicator for the assessment of ecotoxicity risks associated with petrochemical wastes that are generated by the oil refining industry. Long-term exposure to hazardous wastes associated with the petroleum industry may represent a subtle risk to the hematopoietic system in humans. PMID- 11209825 TI - Cybersickness in the presence of scene rotational movements along different axes. AB - Compelling scene movements in a virtual reality (VR) system can cause symptoms of motion sickness (i.e., cybersickness). A within-subject experiment has been conducted to investigate the effects of scene oscillations along different axes on the level of cybersickness. Sixteen male participants were exposed to four 20 min VR simulation sessions. The four sessions used the same virtual environment but with scene oscillations along different axes, i.e., pitch, yaw, roll, or no oscillation (speed: 30 degrees/s, range: +/- 60 degrees). Verbal ratings of the level of nausea were taken at 5-min intervals during the sessions and sickness symptoms were also measured before and after the sessions using the Simulator Sickness Questionnaire (SSQ). In the presence of scene oscillation, both nausea ratings and SSQ scores increased at significantly higher rates than with no oscillation. While individual participants exhibited different susceptibilities to nausea associated with VR simulation containing scene oscillations along different rotational axes, the overall effects of axis among our group of 16 randomly selected participants were not significant. The main effects of, and interactions among, scene oscillation, duration, and participants are discussed in the paper. PMID- 11209827 TI - Adapting verbal protocol methods to investigate speech systems use. AB - This paper presents a method to gather data from user interactions with a speech system. This method is based on existing verbal protocol methods usually used in Cognitive Psychology. The main aim of this method is to elicit the users' expectations and interpretations that are formed when interacting with the system, and can impede the dialogue success when they are erroneous. This article also provides an illustration of the application of this method based on an actual study with a conversational speech system under realistic conditions of use. PMID- 11209826 TI - An investigation of the effects of touchpad location within a notebook computer. AB - This study evaluated effects of the location of a notebook computer's integrated touchpad, complimenting previous work in the area of desktop mouse location effects. Most often integrated touchpads are located in the computer's wrist rest, and centered on the keyboard. This study characterized effects of this bottom center location and four alternatives (top center, top right, right side, and bottom right) upon upper extremity posture, discomfort, preference, and performance. Touchpad location was found to significantly impact each of those measures. The top center location was particularly poor, in that it elicited more ulnar deviation, more shoulder flexion, more discomfort, and perceptions of performance impedance. In general, the bottom center, bottom right, and right side locations fared better, though subjects' wrists were more extended in the bottom locations. Suggestions for notebook computer design are provided. PMID- 11209828 TI - Identification and analysis of unsatisfactory psychosocial work situations: a participatory approach employing video-computer interaction. AB - A method for psychosocial evaluation of potentially stressful or unsatisfactory situations in manual work was developed. It focuses on subjective responses regarding specific situations and is based on interactive worker assessment when viewing video recordings of oneself. The worker is first video-recorded during work. The video is then displayed on the computer terminal, and the filmed worker clicks on virtual controls on the screen whenever an unsatisfactory psychosocial situation appears; a window of questions regarding psychological demands, mental strain and job control is then opened. A library with pictorial information and comments on the selected situations is formed in the computer. The evaluation system, called PSIDAR, was applied in two case studies, one of manual materials handling in an automotive workshop and one of a group of workers producing and testing instrument panels. The findings indicate that PSIDAR can provide data that are useful in a participatory ergonomic process of change. PMID- 11209829 TI - Self-motion perception: assessment by real-time computer-generated animations. AB - We report a new procedure for assessing complex self-motion perception. In three experiments, subjects manipulated a 6 degree-of-freedom magnetic-field tracker which controlled the motion of a virtual avatar so that its motion corresponded to the subjects' perceived self-motion. The real-time animation created by this procedure was stored using a virtual video recorder for subsequent analysis. Combined real and illusory self-motion and vestibulo-ocular reflex eye movements were evoked by cross-coupled angular accelerations produced by roll and pitch head movements during passive yaw rotation in a chair. Contrary to previous reports, illusory self-motion did not correspond to expectations based on semicircular canal stimulation. Illusory pitch head-motion directions were as predicted for only 37% of trials; whereas, slow-phase eye movements were in the predicted direction for 98% of the trials. The real-time computer-generated animations procedure permits use of naive, untrained subjects who lack a vocabulary for reporting motion perception and is applicable to basic self-motion perception studies, evaluation of motion simulators, assessment of balance disorders and so on. PMID- 11209830 TI - The test-retest reliability of a new occupational risk factor questionnaire for outcome studies of low back pain. AB - This study reports the test-retest reliability of a 25-item occupational risk factor questionnaire that can be self-administered in clinical settings and used in outcome studies of low back pain or return to work programs. Subjects were 24 patients (workers on sick leave due to acute low back pain), 29 co-workers on active duty in the same jobs in a utility company, and 53 supervisors. Eighty-six subjects were re-tested within a mean interval of 7-10 days; one group of 20 supervisors was re-tested within 81 days. The questionnaire was self-administered during individual interviews. Reliability was estimated by the kappa statistic as the agreement on the scores within the raters in each group. The agreement ranged from 'slight' (0.15) to 'almost perfect' (0.93) when the re-test interval was less than 43 days. Patients and non-patients were consistent in their assessment of the job demands. rights reserved. PMID- 11209831 TI - Self-reported and measured time of vibration exposure at ultrasonic scaling in dental hygienists. AB - In the present study, our objective was to quantify the daily duration of vibration exposure from ultrasonic scaling in dental hygienists and to compare different methods of self-estimates to time-recorded measurements. The exposure time was self-estimated by use of diary and interview methods in 10 subjects. We found that the measured total daily exposure time was limited, only on average 12min, with a great variation, however, between and within the subjects. Self assessed duration of exposure was overestimated, on average three times higher with a diary and even more at an interview (8 times). In conclusion, the objectively measured exposure time was short and clearly overestimated in self reports. PMID- 11209833 TI - Embedding ergonomics in hospital culture: top-down and bottom-up strategies. AB - In England there has been increasing emphasis on the use of ergonomics to tackle manual handling problems for the last seven years (MHO, 1992, 1998; HSAC, 1998). At Nottingham City Hospital NHS Trust, I have tried to incorporate an ergonomic approach throughout a wide range of activities since 1994. This paper does not seek to report a research project, simply to share the experience of trying to tackle hospital manual handling risks by taking an ergonomic approach. It will explain what this has involved, where it has been successful and where there have been difficulties. In the five years since the implementation of this strategy three measures have been used to monitor trends. These are (1) manual handling incidents: showing a 33% reduction; (2) days lost from musculoskeletal-related sickness absence: 36% reduction; and (3) completed risk actions: rising from 33% completion to over 75% completion. PMID- 11209832 TI - Implementation of a participatory ergonomics program in the rehabilitation of workers suffering from subacute back pain. AB - This paper describes a participatory ergonomics program aimed at early return to regular work of workers suffering from subacute occupational back pain and assesses the perceptions of the participants on the implementation of ergonomic solutions in the workplace. The participatory ergonomics program was used in the rehabilitation of workers suffering from subacute back pain for more than 6 weeks, a program that was associated with an increased rate of return to work. The perceptions of the participatory ergonomics participants were assessed 6 months after completion of the ergonomic intervention through a questionnaire sent to employer representatives, union representatives and injured workers of participating workplaces. About half of the ergonomic solutions were implemented according to the perception of the participants, with a substantial agreement between respondents. PMID- 11209834 TI - A case study in iterative keyboard design using participatory design techniques. AB - Replacing a keyboard can be stressful for operators who take calls all day, particularly when special functions must be sacrificed. This study applied several participatory design techniques to involve over 3,000 operators in the redistribution of function keys on their replacement keyboard. Video analysis and manual data logging methods were surprisingly accurate when measured against software logs. User acceptance was excellent. In the initial cutover program, operator performance levels returned to normal very quickly, resulting in over confidence and unrealistic expectations of post-implementation performance for the remaining call centres because the focus was on the technology rather than on the impact of technology on business benefits. As a consequence, business plan requirements for future projects have now been changed to accommodate predictions of post-implementation performance and taking into account other changes happening at the same time. PMID- 11209835 TI - Standing and very slow walking: foot pain-pressure threshold, subjective pain experience and work activity. AB - Prolonged standing is described as uncomfortable by exposed workers, but the discomfort has not been linked to precise descriptions of workplace activity. We observed 10 sales and kitchen workers ("group 1") who worked standing. We compared the plantar pain-pressure threshold (PPT) of "group 1" (10 standing workers) to that of "group 2" (11 researchers who could choose their posture freely). Group 1 spent an average time of 62% standing still compared to 5% for group 2. Despite the fact that group 1 were primarily confined to defined areas and stood for 62% of the time, their mean time standing still was only 7 s. They walked 35% of the time, but 57% of walking sequences were only one or two steps. Group 1 PPT declined by 23% over the work day compared to 5% among group 2 (p < 0.05, ANOVA). Foot PPT is a promising quantitative indicator of effects of standing work. PMID- 11209836 TI - Influence of measurement accuracy on the application of the 1991 NIOSH equation. AB - A relatively neglected topic in manual materials handling (MMH) research is the impact of the accuracy of task parameter measurements on the application of various assessment methods. A laboratory experiment was conducted to investigate the accuracy of NIOSH equation parameter measurements made by eight subjects following a 4-h training session. Five individual tasks were measured; two were single tasks and three were part of a multiple-component simulated palletizing operation. Significant differences between reference parameter measurements and average measurements made by subjects were found. The sensitivity analysis showed that frequency and horizontal location are the most important parameters. These parameters also tended to have the highest measurement errors. Recommendations for increasing the effectiveness of training programs for NIOSH equation users based on the results of the study are presented. PMID- 11209837 TI - Quantitative nested PCR for human cytomegalovirus DNA: analysis using NucleoScan 2001. AB - A quantitative nested DNA PCR for human cytomegalovirus (CMV) was developed using PCR mimic DNA as an internal standard. A combination of ultra-thin gel and enhanced detection of ethidium bromide-stained PCR bands allowed us to achieve a 25-fold increase in sensitivity over the conventional gel electrophoreses, down to 0.1 ng of DNA per band. When the technique was applied to measuring CMV load in CMV positive leucocyte DNA preparations its sensitivity spanned the range from single to hundreds of CMV DNA copies in 0.1 microg of total white blood cell DNA. PMID- 11209838 TI - Outbreak of aseptic meningitis by echo 4: prevalence of clinical cases among adults. AB - Twenty five cases of meningitis occurred in urban areas surrounding a city (Modena) in Northern Italy, in the period May-July 1999. When the patients were admitted to the Infectious Diseases Division of the University of Modena and Reggio Emilia Hospital and studied by virological and serological methods, the meningitis proved to have an enteroviral origin and enterovirus ECHO 4 type was responsible for all cases of illness. An epidemiological characteristic of the enteroviral meninigitis outbreak was the adult age in 23 out of the 25 patients (mean age 24.50 +/- 7.84 years). The monthly distribution of the aseptic meningitis cases was the following: five cases occurred in May, 13 in June and seven in July. The origin of the spread of the virus infection and the reason for its sudden end remained unknown. The unusual drop in temperature which occurred in the geographic area involved in the aseptic meningitis outbreak at the beginning of August could have interfered with the slowdown in virus circulation. PMID- 11209839 TI - Stability of feline caliciviruses in marine water maintained at different temperatures. AB - Since human caliciviruses are responsible for viral gastroenteritis transmitted by contaminated foods and the viruses barely propagate in cell culture, feline caliciviruses were employed as a model for the measurement of their stability in marine water. Survival of four strains of feline calicivirus in marine water was measured when the seed viruses were diluted 1/10 with marine water and maintained at 4 degrees C, 10 degrees C, and 20 degrees C respectively. Among the virus strains studied, a considerable amount of infective viruses remained at 10 degrees C or lower temperature conditions even for a period of 30 days. PMID- 11209840 TI - Behaviour of the pharmaceutical probiotic preparation VSL#3 in human ileostomy effluent containing its own natural elements. AB - The pharmaceutical probiotic VSL#3 (300 billion cfu/g lactic acid bacteria & bifidobacteria) was inoculated into human ileostomy effluent (HIE) to assess its behaviour vs the ileo-caecal tract. Separately, yogurt bacteria (yog) and bifidobacteria (Bif) present in VSL#3 were also inoculated into HIE. During 37 degrees C incubation (anaerobic condition) at zero, six and 24 hours, both cell growth in control HIE and indigenous Bif growth in HIE+yog were observed. Cells remained viable and metabolically active as shown by the increase in L(+) lactic acid in HIE+VSL#3 and HIE+yog and the pH decreased (approx. 5.5 compared with the 6.2 of control HIE). Total SCFA Short Chain Fatty Acids decreased in HIE+yog and HIE+VSL#3 at 6h and in all cultures at 24h; butyric acid decreased in HIE+Bif and HIE+VSL#3. Generally in vivo the bacteria remain in the ileo-caecal tract no longer than six h, therefore VSL#3 bacteria seem able to pass this barrier viably, colonizing the large bowel. PMID- 11209842 TI - Antimicrobial use and susceptibility rates in isolates from intensive care unit and other nosocomial inpatient and outpatient areas. AB - Our objective was to evaluate the relation between antimicrobial use and susceptibility in the intensive care unit (ICU) and non-ICU inpatient areas in the Bolzano regional hospital. For the isolates of S. aureus, coagulase negative staphylococci, Enterococcus sp., P. aeruginosa and E. coli we found a pattern of significant stepwise decrease in the frequency of antimicrobial susceptibility to penicilloic beta-lactam antibiotics and first generation cephalosporins; the highest senitivity rates occurred among isolates from outpatients, followed in decreasing order by rates among isolates from non-ICU inpatients and from ICU patients; the rate of use of this group of antimicrobial agents was relatively high in the intensive care unit (13,1%). For P. aeruginosa we observed significantly lower susceptibility-rates to second, third and fourth generation cephalosporins, carbapenems and monobactams for non-ICU inpatient areas than for outpatient or ICU areas; this paralleled with the low use of this group of agents in the ICU area (4,9%). Also, for P. aeruginosa the prevalence of susceptibility to ciprofloxacin and norfloxacin in inpatient areas was lower than in the outpatient or ICU-areas; the rate of quinolone-use was relatively low in the ICU area (4,2%). PMID- 11209841 TI - Molecular analysis of Klebsiella pneumoniae strains isolated in pediatric wards by ribotyping, pulsed field gel electrophoresis and antimicrobial susceptibilities. AB - The purpose of this study was to investigate the usefulness of different molecular typing techniques in the surveillance and control of the spread of extended-spectrum-beta-lactamase-(ESBL) producing Klebsiella pneumoniae in the pediatric department of the "Agostino Gemelli" hospital of the Catholic University in Rome, over a period of nine months. The strains were characterized by ribotyping using HindIII as restriction enzyme and pulsed field gel electrophoresis (PFGE) using XbaI as endonuclease. Sixty six K. pneumoniae clinical strains were isolated during this period, the first 32 were isolated in the summer of 1998. Among these first isolates, ribotyping generated 26 different patterns whereas PFGE produced 16 patterns. The remaining 34 strains were isolated during January and April 1999 and all of them were ESBL producers. Ribotyping clustered the strains into 6 patterns whereas PFGE generated only 3 patterns. PCR revealed the presence in 10 isolates of both bla(TEM) and bla(SHV) genes and 24 strains carried only the bla(SHV) gene. In our experience ribotyping revealed a higher power of differentiation with respect to PFGE and was of great help in the surveillance of the infection. PMID- 11209843 TI - Adhesion of a Staphylococcus aureus strain to biomaterials does not select methicillin-resistant mutants. AB - Bacterial adhesion to polymethylmethacrylate and to silicon elastomer, materials frequently used in clinical applications, has been investigated to assess whether adhesion selects methicillin-resistant mutants in the bacterial population in contact with the materials. The methicillin susceptibility of a susceptible Staphylococcus aureus (ATCC 25923) was measured by a modification of plate antibiogram Kirby-Bauer method, which allows optimised detection of small variations in antibiotic susceptibility. In both adherent and non-adherent bacterial subpopulations, the presence of mecA gene, which encodes for the protein PBP 2a responsible for methicillin resistance was searched for by Polymerase Chain Reaction (PCR). The contact with the two polymers did not induce in the bacteria population any phenotypic increase in methicillin resistance, or the selection of mutants carrying the mecA gene. PMID- 11209844 TI - Adhesion to a polymeric biomaterial affects the antibiotic resistance of Staphylococcus epidermidis. AB - The antibiotic-resistance both of adherent bacteria to polymethylmethacrylate (PMMA) and of bacteria which, although exposed to the material, had not undergone adhesion, was measured as bacterial growth inhibition area onto a plate antibiogram, according to Kirby-Bauer and using a dedicated image analyzer system. The adhesion onto PMMA induces a marked (about 30%) increase in resistance to beta-lactam antibiotics (cefamandole, cefazolin, imipenem and ampicillin) and a lower (about 15%) but significant increase to the macrolide erythromycin, to two aminoglycosides (amikacin, netilmicin) and to vancomycin, chloramphenicol and trimethoprim-sulfamethoxazole. PMID- 11209845 TI - Usefulness of genus-specific PCR and Southern blot species-specific hybridization for the detection of imported malaria cases in Italy. AB - A PCR method involving a genus-specific oligonucleotides set and Southern blot hybridization with four species-specific probes to P. falciparum, P. vivax, P. malariae and P. ovale was evaluated for the detection of malaria parasites in blood samples from 101 patients with clinically suspect malaria infection imported to Italy. Plasmodium falciparum was the main species detected. As determined by microscopy, 53 (52.4%) patients had malaria and of these: 40 (75.5%) were infected with P. falciparum; 7 (13.2%) with P. vivax; 1 (1.9%) with P. ovale; 3 (5.7%) with P. malariae; 1 (1.9%) with P. vivax or P. ovale; and 1 (1.9%) with P. falciparum or P. vivax. Ninety-seven out 101 blood samples were submitted to ParaSight-F test which showed a sensitivity of 94.73%, and a specificity of 93.22%, as compared to microscopy. The PCR assay using the genus specific oligonucleotide primer set (pg-PCR) was able to detect 53 (52.4%) infections and showed a sensitivity of 100% and a specificity of 100%, when compared to microscopy. The parasite species were identified by Southern blot hybridization using species-specific probes and 40 (75.5%) samples were P. falciparum positive, 5 (9.4%) P. vivax positive, 4 (7.5%) P. ovale positive, and 2 (3.8%) P. malariae positive. When the Southern blot results were compared to those of blood-film diagnosis, we observed some disagreement. In particular, compared to Southern blot, microscopy underestimated P. ovale infection; blood film analysis recognised only 1 P. ovale sample, whereas Southern blot recognised 4 P. ovale positive samples (by microscopy, 2 of these were detected as P. vivax, 1 as P. ovale or P. vivax, and the other as P. falciparum or P. vivax). Southern blot hybridization was unable to identify one P. falciparum and one P. vivax positive case detected by microscopy. We also plan to use a reference nested-PCR assay to clarify the disagreement observed between microscopy and Southern blot hybridization. PMID- 11209846 TI - Development of a set of multiplex PCR assays for the simultaneous identification of enterotoxigenic, enteropathogenic, enterohemorrhagic and enteroinvasive Escherichia coli. AB - Diarrheagenic E. coli comprise a diverse group of microorganisms responsible for gastrointestinal diseases in humans. On the basis of their virulence traits they are distinguished from the non-pathogenic E. coli and classified in several categories. Molecular methods represent the most reliable techniques for distinguishing pathogenic from non-pathogenic E. coli and characterising their pathogenic features. In this paper we report the development of a set of three multiplex PCR assays for the simultaneous and rapid identification of diarrheagenic E. coli belonging to ETEC, EPEC, EHEC and EIEC groups. Assay 1 utilizes primer pairs specific for genes coding for ST and LT toxins of ETEC, and for the E. coli beta-glucuronidase (uidA); assay 2 detects the presence of the eae and bfpA genes of EPEC, and assay 3 recognizes stx1 and stx2 of EHEC, and ial of EIEC. This technique has been validated on 190 E. coli isolated in Angola, Italy and Mozambique from feces of children with diarrhea. Results obtained with the set of multiplex PCR demonstrated 100% accordance with those obtained for the same isolates by PCR on single target genes. The proposed set of multiplex PCRs is the first reported assay that allows the simultaneous characterization of the four categories of diarrheagenic E. coli. PMID- 11209847 TI - Salmonella typhimurium-endocarditis secondary to an acquired environmental infection: a case report. AB - A diabetic, cardiopathic and anemic 44-year-old farmer presented with a seven-day history of remittent fever with evening peaks. Two months before he had undergone amputation of the V-finger of the left hand secondary to a phlegmon caused by an agricultural injury. Prior to amputation, anaerobic culture analysis of phlegmon pus and selective procedures used to isolate Gram-positive cocci and/or Pseudomonas spp. resulted negative. The diagnosis of endocarditis was supported by isolation of S. typhimurium from blood and by echocardiography showing endocarditic lesions. The source of infection was identified by PCR ribotyping as the same Salmonella typhimurium strain that was present, but not sought, both in the anatomic explanted tissues and from blood samples of the patient. The infection was successfully treated with a combination of gentamicin and ampicillin with consequent improvement in the general clinical picture of the patient. We believe this is the first reported case of S. typhimurium endocarditis secondary to a phlegmon resulting from an environmental source of infection. PMID- 11209848 TI - Identification of Mycobacterium xenopi by gas chromatography. AB - For the purposes of the following study we cultured 32 strains of Mycobacterium xenopi isolated from clinical specimens and several strains of other slowly growing mycobacteria. The cultures were grown in liquid medium and then analysed- after saponification, methylation, extraction with organic solvent and washing of the organic phase--using a highly sensitive manual gas-liquid chromatographic assay for the determination of secondary alcohol 2-OH-docosanol. The percentage of this compound was compared with that previously measured in strains of Mycobacterium xenopi grown on solid medium. The presence of this specific alcohol was always apparent, even though its quantity was lower than that obtained by growing mycobacteria on solid medium. The absence of interference peaks around the compound was checked by analyzing strains of other slowly growing mycobacteria in the same conditions. PMID- 11209849 TI - "In vitro" spontaneous production of B-chemokines by endocervical and endometrial short-term bioptic cultures. AB - Several studies indicate that HIV-1 is present in the cervico-vaginal tissues and secretions of infected women representing an important determinant of both sexual and mother-to-child transmission. HIV-1 genital shedding is influenced by various factors; among these, proinflammatory cytokines, in particular the beta/C-C chemokine group (RANTES, MIP-1alpha and MIP-1beta), are known to suppress HIV-1 replication and thus might affect both sexual and vertical transmission. This study aimed to standardize a procedure to measure "in vitro" uterine spontaneous chemokine production by means of short-term cultures of endocervical and endometrial bioptic fragments. In most cases, "in vitro" chemokine production was observed in both fragment cultures. These results further confirm that beta/C-C chemokines exist in the female genital tract and that uterine mucosa actively produces basal levels of these immuno-active substances. This method constitutes a useful approach to evaluate cytokine production and expression in the female genital tract, their influence on HIV-1 expression and infectivity in this site, and their possible role in viral transmission. PMID- 11209850 TI - A history of plant virology. Cross protection. AB - Cross protection is a type of induced resistance developing in plants against viruses. Its basis is that prior infection with one virus affords protection against closely related ones. Its history started about seventy years ago, when the Dutchman Thung and the Englishman Salaman described the phenomenon independently. During the 1930s, several virologists confirmed the discovery, which was considered the first possibility to protect plants against virus infection. Growing interest also led plant virologists to formulate the first hypotheses on its mechanism, with the onset of a still unsolved debate. The hypotheses, that have been succeeded until the 1970s, included (i) antibody formation, (ii) exhaustion of essential metabolites, (iii) limited sites for virus multiplication, and (iv) specific adsorption by new cell compounds. These hypotheses were re-proposed and discussed on several occasions without arriving at a final conclusion. The statement of molecular genetics of viruses produced new interesting "theories", fundamentally based on the interference between virus strains. A model developed by the Americans Palukaitis and Zaitlin in 1984 indicates that excess of progeny positive-sense RNA of the protecting strain would sequester the minus-strand RNA of the challenging strain. Other models involve a function of the coat protein, or gene recombination. However, no model that could unify all the various facets of cross protection has hitherto been proposed. All that has not stopped the phenomenon having practical application. From the first attempts against a severe disease of cocoa in West Africa realized by Posnette in the 1940s, a number of crops (such as tomato, tobacco, citrus, cucurbits, grapevine, soybean, papaya, and so on) have been submitted to this practice. During the 1980s, cross protection came to a standstill because of the development of new resistant or tolerant cultivars. Its story is by no means ended, and much work is needed to understand its limits and possibilities. PMID- 11209851 TI - Protonation effects on the inclusion complexation of 6-deoxy-6-diethylamino-beta cyclodextrin with 2-anthracenesulfonate, 2-naphthalenesulfonate, 2,6 naphthalenedisulfonate, and 2,7-naphthalenedisulfonate in aqueous solutions. AB - At pH values 5.5 and 10.3, 6-deoxy-6-diethylamino-beta-cyclodextrin (DD-beta-CD) as well as beta-CD forms 1:1 inclusion complexes with 2-anthracenesulfonate (2AS), 2-naphthalenesulfonate (2NS), 2,6-naphthalenedisulfonate (2,6NDS), and 2,7 naphthalenedisulfonate (2,7NDS). The equilibrium constants (K) for the formation of the 1:1 inclusion complexes have been evaluated from the absorbance and/or fluorescence intensity changes. With respect to the beta-CD inclusion complexes of 2AS, 2NS, 2,6NDS, and 2,7NDS, the K values at pH 5.5 are nearly the same as the corresponding ones at pH 10.3. In the case of the DD-beta-CD inclusion complexes, the K values of 2AS and 2NS similarly do not depend on the pH value. However, the K values of 2,6NDS and 2,7NDS for DD-beta-CD at pH 5.5 have been found to be more than two times greater than the corresponding ones at pH 10.3, suggesting the electrostatic attraction between the protonated diethylamino group of DD-beta-CD and the sulfonato group of the NDSs. PMID- 11209852 TI - Vibrational spectra of succinonitrile and its [1,4-13C2]-,[2,2,3,3,-2H4]- and 1,4 13C-2,2,3,3-2H4]-isotopomers and a force field of succinonitrile. AB - [1,4-13C2]-succinonitrile, [2,2,3,3-2H4]-succinonitrile, [1,4-13C2-2,2,3,3-2H4] succinonitrile have been synthesized and, for the first time, the infrared and Raman spectra of these succinonitrile isotopomers have been discussed in detail. The spectra were recorded at ambient temperature and at the temperature of liquid nitrogen and assignments of the vibrational bands of all above isotopomers have been made. In addition to this, the force field of succinonitrile in its two configurations, gauche and trans, have been calculated using all experimental frequencies and the ab-initio method. Also, the assignments of the vibrational bands of the 'normal' succinonitrile molecule have been achieved using the results of the force field calculations to support the assignments for the normal succinonitrile, as well as for the isotopomers. PMID- 11209853 TI - Identification and estimation of extra-framework aluminium in acidic mazzite by diffuse reflectance spectroscopy. AB - Diffuse reflectance spectroscopy has been used to investigate structural modification of mazzite zeolite subjected to calcination, acid leaching and acetylacetone treatments. Extra-framework aluminium species, formed upon expulsion of aluminium from the framework, are detected by DRS because they are involved in aluminium-oxygen charge transfer transitions. Impregnation of the calcined ammonium-exchanged and acid leached samples with ethanolic acetylacetone will convert the broadened 260-280 nm band of extra-framework aluminium with distorted symmetry to a distinct well-defined 285 nm band. The appearance of this band is due to the transformation of the aluminium atoms with a different coordination number to structures with highly ordered octahedral symmetry. Washing the acetylacetone treated samples with hot ethanol leads to extraction of some of the complexed aluminium. The presence of an extracted aluminium triacetylacetonate complex in the eluant is verified by the same spectrophotometer used in its conventional mode. This suggests that a dual DR and UV-VIS spectrophotometry is an appropriate approach to study such topics. PMID- 11209854 TI - Vibrational study on structural transitions of potassium pelargonate CH3(CH2)7CO2K. AB - Anhydrous potassium pelargonate (KC9) undergoes four thermal transitions from room temperature to 450 degrees C. A normal mode analysis was made for the molecule in phase I at room temperature and the molecule was considered to have an all-trains conformation. With increasing temperature, partial melting of the alkyl chains occurred in phase II and complete melting was observed in phase III, as confirmed by vibrational spectra. In addition, orientational disorder of the carboxylate groups was suggested in phase II. This transition behavior of potassium pelargonate was compared with the behavior of nonane and pelargonic acid. PMID- 11209855 TI - Water in toluene revisited: vibrational patterns in the stretching region. AB - The symmetric (v1) and antisymmetric (v3) stretching bands of water monomers in toluene are revisited using two approaches: (i) calculation of dipole autocorrelation functions (ii) the solvatochromic behaviour of both vibration frequency shifts. The time constants extracted from the autocorrelations account for meaningful differences between the couplings established by the antisymmetric and symmetric vibrations with the solvent. The dipole autocorrelation function for the symmetric stretching band fits well a Lorentzian spectral density and shows a higher contribution to hindered rotation relatively to the one obtained from the antisymmetric stretching. The spectral shifts of stretching frequencies in toluene and in other relevant solvents were interpreted as arising from the electronic and orientational polarisations. Characteristic donor/acceptor interactions also contribute to the red shift and were tested by using empirical solvent basicity scales such as Kamlet-Taft beta and the recently proposed SB. The deviations detected in toluene as regards the continuum dielectric predictions are quantitatively treated and account for the specific interaction between the water and the molecular pi electron system referred to in the literature. PMID- 11209856 TI - Spectroscopy study on the photochromism of Schiff bases N,N'-bis(salicylidene) 1,2-diaminoethane and N,N'-bis(salicylidene)-1,6-hexanediamine. AB - The photochromism of Schiff bases N,N'-bis(salicylidene)-1,2-diaminoethane (BSE) and N,N'-bis(salicylidene)-1,6-cyclohexanediamine (BSH) was studied by steady state and time-dependent fluorescence, UV Vis absorption spectroscopy and theoretical chemistry calculations. The experimental results show that BSH can perform the photochromism easier than BSE, may be due to the molecular topology difference. PMID- 11209857 TI - Aggregate formation of Rhodamine 6G in anisotropic solvents. AB - The aggregation of Rhodamine 6G in liquid crystalline solutions was studied using polarised spectroscopy and in a guest-host system based on homogeneous homeotropic alignment. The orientation of the dye molecules (guest) was controlled using an electric field, and this enabled the contrast ratio R of the dye to be obtained by electrically switching. The excitonic treatment of the absorption spectra suggests a coplanar structure for the dimeric aggregates. PMID- 11209858 TI - Towards a single crystal Raman spectrum of kaolinite at 77 K. AB - The Raman spectra at 77 K of the hydroxyl stretching of kaolinite were obtained along the three axes perpendicular to the crystal faces. Raman bands were observed at 3616, 3658 and 3677 cm(-1) together with a distinct band observed at 3691 cm(-1) and a broad profile between 3695 and 3715 cm(-1). The band at 3616 cm(-1) is assigned to the inner hydroxyl. The bands at 3658 and 3677 cm(-1) are attributed to the out-of-phase vibrations of the inner surface hydroxyls. The Raman spectra of the in-phase vibrations of the inner-surface hydroxyl-stretching region are described in terms of transverse and longitudinal optic splitting. The band at 3691 cm(-1) is assigned to the transverse optic and the broad profile to the longitudinal optic mode. This splitting remained even at liquid nitrogen temperature. The transverse optic vibration may be curve resolved into two or three bands, which are attributed to different types of hydroxyl groups in the kaolinite. PMID- 11209859 TI - Spectroscopic study on the photoinduced reaction of fullerene C60 with aliphatic amines and its dynamics--strong short wavelength fluorescence from the adducts. AB - The photoinduced electron donor acceptor interactions of C60 with eight kinds of aliphatic amines, namely dicthylamine (DEA), triethylamine (TEA), tri-n-amylamine (TAA), propylethylamine (PPA), n-butylamine (BTA), n-heptylamine (HPA) and dodecylamine (DDA) and ethylenediamine (EDA) are reported by a comprehensive spectroscopic study. Experiments show that there is a good discipline with different structure and the length of n-alkyl group both in their ground and excited states. At the same time, a slow reaction takes place between C60 and various amines with a gradual increase in the concentration of various aliphatic amines or the standing of solution, which can be dramatically catalyzed by UV radiation. The final products can all emit a strong fluorescence at the relatively shorter wavelength around 519 nm. On this basis, the dynamic properties of C60/aphaliticamines including the enthalpy of activation (deltaH++et) and entropy activation (deltaS++et), together with all sorts of influence factors are firstly investigated in this work. The possible reaction mechanisms are explored, also. PMID- 11209861 TI - Near infrared spectra (4000-10 500 cm-1) of phenol-OH and phenol-OD in carbon tetrachloride. AB - The near infrared spectra (3800-10 500 cm(-1) of phenol-OH and phenol-OD are studied in carbon tetrachloride solution. The bandwidth of the v(OH) and v(OD) stretching vibrations increases with the vibrational quantum number in contrast to results obtained by nonresonant ionization spectroscopy (S.I. Ishiuchi et al., Chem. Phys. Lett. 283 (1998) 243). The bandwidth of the v(CH) vibrations obtained by a deconvolution procedure also increases with the frequencies associated with the vibrational transitions. The anharmonicity of the v(CH) vibrations ranges between 51 and 72 cm(-1). Numerous absorptions are observed in the near infrared spectra. These absorptions are tentatively assigned to combinations involving the fundamental transitions which have been recently calculated at different levels of theory (D. Michalska et al., J. Phys. Chem. 100 (1996) 17786). The experimental, theoretical and harmonic v(OH) and vi(CH) frequencies are compared. PMID- 11209860 TI - Photophysical properties of 2,5-diphenyl-1,6,6a-trithiapentalene revealed by time resolved spectroscopy. AB - The fluorescence decay from S2(pi, pi*) state of 2,5-diphenyl-1,6,6a trithiapentalene (DP-TTP) in cyclohexane, tetrahydrofuran and acetonitrile solutions of a quantum yield of approximately 0.02-0.04 were measured. The results indicate that, the dominant process of radiationless deactivation of the S2 state, is internal conversion to the S1 state. Upon laser pulse excitation (lambda(ex) = 532 nm) from the S1(pi, pi*) state, DP-TTP in deoxygenated benzonitrile, acetonitrile, ethanol and tetrahydrofuran solutions give rise to transient triplet triplet absorption (lambdaTmax = 700-720 nm). Kinetic data are presented for intrinsic triplet lifetimes, self-quenching and quenching by oxygen. PMID- 11209862 TI - Complex formation in the indolo[2,3-b]quinolines--methylene blue systems in aqueous solutions. AB - Changes in the absorption spectra of methylene blue (MB) aqueous solutions containing an indoloquinoline can be described by assuming complex formation between MB and the indolinoquinoline. At the low concentration range of the two reactants a simple 1:1 complex stoichiometry was postulated on the basis of the Benesi-Hildebrand, Scott and Scatchard linearization of spectroscopic data and augmented by the formation of an isosbestic point. The estimated association constants were correlated with the ab initio calculated electronic properties of indolo[2,3-b]quinolines. PMID- 11209863 TI - Interfacial study of benzenesulfinate chemisorbed on silver. AB - The oxidative stability of self-assembled monolayer (SAM) of thiols on silver was examined with matrix-assisted laser desorption ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS). A benzenesulfinate (BS) monolayer on silver was also prepared and investigated with MALDI-TOF-MS and surface-enhanced Raman scattering (SERS). The presence of sulfinate, sulfonate, and thiosulfonate fragment ions reveals that thiolate monolayers oxidize in the air. The relative abundance of C6H5SO2- and C6H5SO3- species in the mass spectra of the monolayer with different air-exposure times provides an estimation of the oxidation progress. In the vibrational spectrum, the large red shift of v(SOO-), combined with the lack of a shift of v(C-S) upon adsorption, indicates its bidentate O coordination. The orientation of the confined molecules, based on the Raman surface selection rules, was derived from the preferential enhancement of the different functional groups. The benzene ring of BS was found almost normal to the metal surface as a result of the intermolecular forces; that geometry excludes the possibility of the pi-system of the benzene ring from participating as another binding site. The SER spectra of BS obtained via a selective etching process confirms these observations. PMID- 11209864 TI - The surface enhanced Raman scattering effects of composite nanocrystals of Ag TiO2. AB - The composite particles of Ag-TiO2 both in a nanocrystal form was prepared by photoreduction of AgNO3 in the rutile colloidal solution. The surface plasmon absorption (SPA) band of the silver clusters supported on the TiO2 nanocrystal was red shift, and a strong surface enhanced Raman scattering (SERS) effect for the composite particles of Ag-nanocrystalline TiO2 was observed. The SERS effect is relating to the red shift phenomenon of SPA band, which could be explained by induced-resonance effect. PMID- 11209865 TI - Excited-state dipole moments of some hydroxycoumarin dyes using an efficient solvatochromic method based on the solvent polarity parameter, EN(T). AB - Excited-state dipole moments of some hydroxycoumarins, extensively used as laser dyes, have been determined using the solvatochromic method based on the microscopic solvent polarity parameter EN(T). Agreement between experimental and Austin model 1 (AM 1) calculated dipole moment changes has been found to be close in most of the cases. Our results are expected to be quite reliable in view of the fact that the correlation of the solvatochromic Stokes shifts is superior to that obtained using bulk solvent polarity functions. The dipole moments in the excited state, for all the molecules investigated, are higher than the corresponding values in the ground state. The increase in dipole moment upon excitation has been explained in terms of the nature of emitting state and resonance structure. PMID- 11209866 TI - Spectral studies on metal-ligand bonding in complexes of 1-acetyl-2 (coumariniminecarboxamide-3-yl)hydrazine. AB - Several new transition metal complexes derived from 1-acetyl-2 (coumariniminecarboxamide-3-yl)hydrazine (HL) have been prepared and characterized by elemental analyses, 1H-NMR, magnetic susceptibility, IR, UV, EPR and thermal analyses. Stereochemistries are proposed for the complexes on the basis of the spectral and magnetic studies. The i.r. data indicate that the carbonyl oxygen of the carboxamide constituents chelating backbone in most complexes. The visible and EPR spectral studies indicated that the Cu(II) complexes have a tetragonal geometry. From the EPR spectrum of the Cu(II) complexes, various parameters were calculated. PMID- 11209867 TI - Quantum chemistry predicted correlations between geometric isomerism (conformation) of -OH and =NH substituents and typical group frequencies of nucleic acid bases: cytosine. AB - Results of a search for correlations between typical group mode frequencies and conformation of -OH and =NH substituents is reported. The study is based on quantum chemical data (HF/6-31G (d, p) and MP2 (full)/6-31G (d, p) approximations) of 13 isomers of cytosine. It is closely related to investigations of stability and energetics of all isomers of the more common nucleic acid bases, which revealed correlations between conformation (geometric isomerism) of OH and =NH substituents on the one hand and conversion energies, relaxation of internal structural parameters, electric field gradients, etc. on the other hand. In the majority of cases alteration of conformation of these substituents is accompanied by systematic frequency shifts of stretching, in plane and out-of-plane bending (torsional) modes conventionally assigned to such groups and by alteration of quantum chemically predicted estimates of harmonic valence force constants and structural parameters dominating the mode frequencies. For identification of group modes 'fractional' mass (other than 'natural' mass) isotope shifts of frequency and normal vectors proved useful. Likewise, estimation of effects of force constant and structural parameter alterations on frequency shifts by first order perturbation theory of the FG problem of partial structures contributed valuable insight into the origin of the shifts. PMID- 11209868 TI - Fourier transform Raman spectroscopy of Syncrude sweet blend distillation fractions derived from Athabasca bitumen. AB - The C-H stretching region in FT-Raman spectra of Syncrude sweet blend (SSB) and three distillation fractions (naphtha, light gas oil and heavy gas oil) was analyzed in detail in this investigation. The frequencies and intensities of the 11 aliphatic and three aromatic C-H bands used to fit the spectrum of SSB were equal to the averages (weighted sums) of the corresponding quantities in the spectra of the fractions. The additivity of the spectra, thought to be a consequence of the large number of discrete compounds contained in each fraction, makes it possible to estimate the composition of other SSB samples using the spectra of the fractions reported in this work. In the aromatic C-H region, total intensities can be used to calculate the distribution of aromatics among the distillation fractions; these data also permit calculation of the fractional aromaticity (per cent aromatic carbon) for SSB and each fraction, with accuracies comparable to those obtained using NMR spectroscopy. PMID- 11209869 TI - Approximate molecular orbital anharmonic parameters for the infrared spectrum of H2O. AB - The vibrational spectrum of H2O was calculated at MP2/6-31G(extended) and MP2/6 311G* levels taking into account anharmonicities through a simple approach to second-order perturbation theory in which molecular energy and dipole moment are expanded as Taylor series in normal coordinates with no cross terms, to simplify calculations. The series coefficients are obtained separately for each normal coordinate through polynomial regression of calculated single point property values corresponding to a few distorted molecular geometries. The energy coefficients are used to calculate the harmonic frequencies and the chi(ii) anharmonicity constants, and so the band origins. For the band intensities, second-order perturbation theory equations derived earlier for diatomic molecules are used for each mode. Estimated frequencies have accuracy equivalent to those of previous complete perturbation calculations at the same ab initio levels, being at most 2.6% above the experimental values for the MP2/6-31G(extended) level. The fundamental intensity estimates are equivalent to those for the complete treatments, with the exception of that at MP2/6-31G(extended) level for the bending mode, which is 7% above the experimental value. Estimated overtone intensities by both complete treatments and the simple approach may still differ in magnitude from the experimental values, though to a lesser extent for the formers. PMID- 11209870 TI - Core molecular orbital contribution to N2O isomerization as studied using theoretical electron momentum spectroscopy. AB - Core molecular orbital contribution to the electronic structure of N2O isomers has been studied using quantum mechanical density functional theory combined with a plane wave impulse approximation method. Momentum distributions of wave functions for inner shell molecular orbitals of the linear NNO, cyclic and linear NON isomers of N2O are calculated through the (e, 2e) differential cross sections in momentum space. This is possible because this momentum distribution is directly proportional to the modulus squared of the momentum space wave function for the molecular orbital in question. While the momentum distributions of the NNO and cyclic N2O isomers demonstrate strong atomic orbital characteristics in their core space, the outer core molecular orbitals of the linear NON isomer exhibit configuration interactions between them and the valence molecular orbitals. It is suggested that the frozen core approximation breaks down in the prediction of the electronic structure of such an isomer. Core molecular orbital contributions to the electronic structure can alter the order of total energies of the isomers and lead to incorrect conclusions of the stability among the isomers. As a result, full electron calculations should be employed in the study of N2O isomerization. PMID- 11209871 TI - Experimental and ab initio MO studies on the IR spectra and structure of pyridinium dicyanomethylide and trimethylammonium dicyanomethylide. AB - The structures of the title ylides have been studied by both quantitative infrared (IR) spectra and ab initio HF and MP2 force field calculations. Good agreement has been found between theoretical and experimental data for their spectral and structural characteristics. According to both IR data and geometry parameters the dicyanomethide groups in the ylides studied have a pronounced carbanionic character. The analysis of the calculated net electric charges however shows only moderate (below 0.6 e-) intramolecular charge transfers between the pyridinium (trimethylammonium) and dicyanomethide fragments of the species studied. PMID- 11209872 TI - Interobserver repeatability and validity of an observation method to assess physical loads imposed on the upper extremities. AB - Interobserver repeatability and validity were assessed for a new semiquantitative, time-based observation method for the estimation of physical loads imposed on the upper extremities. Six risk factors of upper extremity disorders were included in the method: repetitive use of hand, use of hand force, pinch grip, non-neutral wrist posture, elevation of upper arm, local mechanical pressure. Two occupational health nurses were trained to use the method. They observed 127 work cycles at a food-processing plant and a paper mill. The method was validated against expert observations from the video, continuous recordings of myoelectric activity (EMG) of forearm muscles, and wrist posture measured with goniometers. Interobserver repeatability was good or moderate for repetitive use of hand, hand force, pinch grip (range kappa = 0.58-0.71 on the right; 0.60-0.61 on the left side). Interobserver repeatability was moderate or poor for non neutral wrist posture, elevation of the upper arm and local mechanical pressure. Validity ranged from moderate to good for repetitive use of hand, use of hand force, pinch grip and non-neutral wrist posture when expert observation was used as reference standard. When observations were validated against force estimations (EMG) and wrist goniometer data, validity was poor. In the absence of generally accepted reference values, arbitrarily chosen limits were used for the proportional duration of some physical load factors. Studies should be carried out to assess the limits that best differentiate between safe and hazardous jobs. PMID- 11209873 TI - Mobile (cellular) phone use and driving: a critical review of research methodology. AB - Studies have examined possible effects of concurrent mobile phone use on driving performance. Although interference is often apparent, determining the implications of such findings for 'real world' driving is problematic. This paper considers some relevant methodological issues including the definition of procedures and terms, operationalization of task elements, sampling of task components, and the provision of experimental controls. Suggestions are made about how methodological rigor could be improved. PMID- 11209874 TI - A quantitative model of work-related fatigue: background and definition. AB - Fatigue has been identified as a major risk factor for shiftworkers. However, few organizations or governments currently manage work-related fatigue in any systematic or quantitative manner. This paper outlines an approach to managing fatigue that could improve shiftwork management. Using shift start and finish times as an input, the outlined model quantifies work-related fatigue on the basis of its known determinants; that is shift timing and duration, work history and the biological limits on sleep length at specific times of day. Evaluations suggest that work-related fatigue scores correlate very highly with sleep-onset latency, neurobehavioural impairment and subjective sleepiness. The model is useful in that it allows comparisons to be made between rosters independent of shift length and timing or the total number of work hours. Furthermore, unlike many models of sleepiness and fatigue, individual's sleep times are not required as hours of work are used as the input. It is believed the model provides the potential quantitatively to link the effects of shiftwork to specific organizational health and safety outcomes. This simple approach may be especially critical at a time when many organizations view longer and more flexible hours from their employees as an immediate productivity gain. PMID- 11209875 TI - Impact of added rest breaks on the productivity and well being of workers. AB - The impact of frequent short rest breaks on the productivity and well being of a group of 30 workers in a meat-processing plant was studied. Two rest break schedules were tested, both of which provided 36 min of extra break time over the regular break schedule (30-min lunch and two 15-min breaks). In the first experimental rest break schedule, workers were given 12 3-min breaks evenly distributed over the workday (3-min break for every 27 min of work). In the second schedule, workers were given four 9-min breaks evenly distributed over the workday (9-min break every 51 min of work). Outcome measures included production rate and discomfort and stress ratings. Results showed that neither of the two experimental rest break schedules had a negative effect on production, and the 9 min break schedule improved discomfort ratings for the lower extremities. The workers in the study mostly preferred the 9-min rest break schedule, indicating that workers in general might not as readily accept fragmentation of break time into short, frequent breaks. PMID- 11209876 TI - Abstract and reduced-context representations in fault-finding training. AB - The ability to transfer problem-solving expertise to new situations is regarded as an important practical skill but it is known to be sensitive to contextual differences. Employing abstract and reduced-context training tasks has been proposed as a method of fostering transferable skill but the evidence supporting this approach is limited. The research reported here aimed at assessing the effectiveness of training with diagnostic tasks of varying degrees of contextual detail. The criterion test used to measure training effectiveness was a context rich diagnostic task that involved locating faults in a representation of a water supply and drainage system (WSDS). In the first study reported (baseline study), subjects were trained and tested on the WSDS task. Various training interventions were employed and a set of diagnostic heuristics proved to be the most effective. Two pilot studies were then carried out to determine whether training with abstract diagnostic tasks could produce transfer to the criterion test, the WSDS. Little evidence of transfer was found; therefore, it was decided to incorporate some context into training but not so much as to obscure important, conceptual task features. This was achieved by constructing reduced-context representations (RCO) of the WSDS at more than one level of abstraction (main study). Training with those representations took less time than training with the WSDS but transfer to the criterion test (the WSDS) was equally efficient. During training with the RCO representations, a technique of refusing costly test information was employed which is thought to have helped subjects discover efficient search strategies and consistently transfer them to the criterion test. This was contrasted with the verbal diagnostic heuristics of the baseline study, which had proved to be effective, but which were not always transferred consistently to the criterion test. This raises the question as to whether diagnostic strategies are necessarily best conveyed solely in verbal form, if the intention is to train transferable skill. PMID- 11209877 TI - Gender differences in lifting technique. AB - The importance of different motion patterns in the assessment of work technique is rarely addressed in the literature and even less information can be found regarding gender differences. In this study the possible gender differences in lifting technique from lifting experiments on 12 female and 10 male participants were examined. The participants performed squat and stoop lifts of a box. Movements were measured by means of opto-electronic measurement systems. Kinematic data derived from the measurements revealed some differences between the men and the women, e.g. in trunk motion and knee angle ranges. The hip-knee interjoint coordination was more synchronized for women than for men in terms of the relative phase angle. It is concluded that so far gender differences in motion patterns have not been sufficiently explored and that men and women need to be considered separately in the evaluation of work technique in manual handling tasks. Advantages and disadvantages of different coordination patterns need to be further investigated. PMID- 11209878 TI - The use of mirrors during an assembly task: a study of ergonomics and productivity. AB - Industrial assembly tasks often require awkward, sustained neck and/or shoulder postures that can lead to increased musculoskeletal discomfort and reduced productivity. The aim of this study was to investigate the effects of mirror and periscope visual aids as ergonomic interventions designed to eliminate awkward postures of the cervicobrachial region during assembly tasks. Participants simulated a simple assembly task by using a cordless screwdriver to drive screws into a pre-tapped aluminium block. Trials of 15 min were run for each of four distinct assembly workstation configurations: industry standard (in-line screwdriver, work at elbow height, no visual aid); pistol grip (pistol grip screwdriver, work at shoulder height, no visual aid); mirror (in-line screwdriver, work at elbow height, single mirror visual aid); and periscope (in line screwdriver, work at elbow height, two-mirror visual aid system). Muscular activity, discomfort, body posture, productivity and operator subjective assessment were recorded to determine the effects of the visual aid interventions. The results show that when comparing the interventions to the industry standard condition, there was a 45% reduction in average cervical erector spinae activity, a 90% reduction in average neck flexion angle and a 72% reduction in neck discomfort with the interventions. When comparing these interventions to the pistol grip condition there was an 80% reduction in activity of the dominant side deltoid, a 92% reduction in shoulder flexion angle and an 81% decrease in shoulder discomfort with the interventions. Productivity was greatest in the industry standard configuration followed by the pistol grip (9% lower), the periscope (13% lower) and the mirror (23% lower) configurations. A follow-up study that compared the productivity of the periscope configuration with that of the industry standard configuration showed that within a 4-h work period this productivity differential decreased by over 33%. PMID- 11209879 TI - Antiquity of the biological sulphur cycle: evidence from sulphur and carbon isotopes in 2700 million-year-old rocks of the Belingwe Belt, Zimbabwe. AB - Sulphur and carbon isotopic analyses on small samples of kerogens and sulphide minerals from biogenic and non-biogenic sediments of the 2.7 x 10(9) years(Ga) old Belingwe Greenstone Belt (Zimbabwe) imply that a complex biological sulphur cycle was in operation. Sulphur isotopic compositions display a wider range of biological fractionation than hitherto reported from the Archaean. Carbon isotopic values in kerogen record fractionations characteristic of rubisco activity methanogenesis and methylotrophy and possibly anoxygenic photosynthesis. Carbon and sulphur isotopic fractionations have been interpreted in terms of metabolic processes in 2.7 Ga prokaryote mat communities, and indicate the operation of a diverse array of metabolic processes. The results are consistent with models of early molecular evolution derived from ribosomal RNA. PMID- 11209880 TI - Genetic variation in a Pacific Island land snail: population history versus current drift and selection. AB - Previous studies of Partula land snails from the Society Islands, French Polynesia, have shown that there can be striking differences in shell shape, colour and banding pattern between nearby populations, even in the absence of any obvious geographical barriers to the movement of snails, or environmental gradients. Elsewhere, there may be relative uniformity over large distances. Analysis of a mitochondrial gene from Partula taeniata (Morch) shows a similar pattern. The relative frequencies of two mitochondrial haplotypes change abruptly over small distances, seemingly independent of the environment. Although the transition roughly coincides with clines in the frequencies of some morphological characteristics, it appears to be unrelated to others. It is likely that many of the differences accumulated while populations were isolated from one another, through the effects of random genetic drift and selection. Isolation of populations may have occurred as a result of demographic changes, or during the process of colonization if occasional long-distance migrants establish populations ahead of the main invading front. Current genetic drift, even without restrictions to gene flow, may contribute to genetic patchiness on a small scale, although it is likely that conspicuous characteristics such as shell colours and banding patterns are also influenced by selection. PMID- 11209881 TI - Selective extinction and rapid loss of evolutionary history in the bird fauna. AB - The extinction of species results in a permanent loss of evolutionary history. Recent theoretical studies show that this loss may be proportionally much smaller than the loss of species, but under some conditions can exceed it. Such conditions occur when the phylogenetic tree that describes the evolutionary relationships among species is highly imbalanced due to differences between lineages in past speciation and/or extinction rates. I used the taxonomy by C. G. Sibley and B. L. Monroe Jr to estimate the global loss of bird evolutionary history from historical and predicted extinctions, and to quantify the ensuing changes in balance of the bird phylogenetic tree. In the global bird fauna, evolutionary history is being lost at a high rate, similar to the rate of species extinction. The bird phylogenetic tree is highly imbalanced, and the imbalance is increased significantly by anthropogenic extinction. Historically, the elevated loss of bird evolutionary history has been fuelled mostly by phylogenetic non randomness in the extinction of species, but the direct effect of tree imbalance is substantial and could dominate in the future. PMID- 11209882 TI - Back-casting sociality in extinct species: new perspectives using mass death assemblages and sex ratios. AB - Despite 150 years of interest in the ecology of dinosaurs, mammoths, proto hominids and other extinct vertebrates, a general framework to recreate patterns of sociality has been elusive. Based on our recent discovery of a contemporary heterospecific mass death assemblage in the Gobi Desert (Mongolia), we fit predictions about gender-specific associations and group living in extant ungulates to extinct ones. We relied on comparative data on sex-ratio variation and body-size dimorphism, basing analyses on 38 additional mass mortality sites from Asia, Africa, Europe and North America that span 50 million years. Both extant and extinct species died in aggregations with biased adult sex ratios, but the skew (from 1:1) was greater for extinct dimorphic taxa, suggesting that sociality in these extinct species can be predicted from spatial and demographic traits of extant ones. However, extinct rhinos, horses and zebras were inconsistent with predictions about adult sex ratios, which underscores the inherent difficulty in backcasting historic patterns to some monomorphic taxa. These findings shed light not only on the sociality of extinct species but provide a sound, although limited, footing for interpretation of modern death assemblages within the context of the emerging science of taphonomy and palaeobehaviour. PMID- 11209883 TI - Explaining social learning of food preferences without aversions: an evolutionary simulation model of Norway rats. AB - Norway rats (Rattus norvegicus) transmit preferences for novel foods socially by smelling each other's breath. However, rats fail to learn aversions, acquiring a preference even if the rat whose breath they smell has been poisoned. Rats can distinguish between sick and healthy conspecifics and social learning of both preferences and aversions is present in other species - hence it is unclear why rats cannot learn aversions socially. We constructed an evolutionary simulation in which a population of rats foraged from a central location, exploiting food sites that could contain edible or toxic foodstuffs. We examined the relationship between toxin lethality and selection for individual versus social learning and discrimination between sick and healthy conspecifics in order to allow learning of both preferences and aversions. At low lethality levels individual learning was selected for and at intermediate levels we found social learning of both preferences and aversions. Finally, given high lethality levels the simulated rats would employ social learning but failed to learn aversions, matching the behaviour of real rats. We argue that Norway rats do not learn aversions socially because their environment may contain only highly lethal toxins which make interaction with a sick conspecific an extremely rare event. PMID- 11209884 TI - Feeding behaviour of free-ranging penguins determined by oesophageal temperature. AB - Sea birds play a major role in marine food webs, and it is important to determine when and how much they feed at sea. A major advance has been made by using the drop in stomach temperature after ingestion of ectothermic prey. This method is less sensitive when birds eat small prey or when the stomach is full. Moreover, in diving birds, independently of food ingestion, there are fluctuations in the lower abdominal temperature during the dives. Using oesophageal temperature, we present here a new method for detecting the timing of prey ingestion in free ranging sea birds, and, to our knowledge, report the first data obtained on king penguins (Aptenodytes patagonicus). In birds ashore, which were hand-fed 2-15 g pieces of fish, all meal ingestions were detected with a sensor in the upper oesophagus. Detection was poorer with sensors at increasing distances from the beak. At sea, slow temperature drops in the upper oesophagus and stomach characterized a diving effect per se. For the upper oesophagus only, abrupt temperature variations were superimposed, therefore indicating prey ingestions. We determined the depths at which these occurred. Combining the changes in oesophageal temperatures of marine predators with their diving pattern opens new perspectives for understanding their foraging strategy, and, after validation with concurrent applications of classical techniques of prey survey, for assessing the distribution of their prey. PMID- 11209885 TI - Pyrazine odour makes visually conspicuous prey aversive. AB - Unpalatable insects frequently adopt multimodal signals to ward off predators, incorporating sounds and odours into their colourful displays. Pyrazine is an odour commonly used in insect warning displays, and has previously been shown to elicit unlearned biases against common warning colours, e.g. yellow and red in naive predators. We designed two experiments to test for similar effects of pyrazine on the conspicuousness of prey, perhaps the most ubiquitous aspect of aposematic coloration. In the first experiment, we offered predators (Gallus gallus domesticus) a choice between conspicuous crumbs and cryptic crumbs in the presence or absence of pyrazine. In the second experiment, we manipulated the birds' experience of conspicuous prey during an initial training phase. Only in the presence of pyrazine did birds show a bias against conspicuously coloured food, and this occurred whether or not they had previously experienced food that contrasted with the background. This emergent behaviour relied upon the visual and odorous signal components being presented together. These unlearned, yet hidden, responses against conspicuousness demonstrate that there are initial benefits to prey being conspicuous when the multimodal nature of warning signals is accounted for. PMID- 11209886 TI - Primer effects of a brood pheromone on honeybee behavioural development. AB - Primer pheromones are thought to act in a variety of vertebrates and invertebrates but only a few have been chemically identified. We report that a blend of ten fatty-acid esters found on the cuticles of honeybee larvae, already known as a kairomone, releaser pheromone and primer pheromone, also act as a primer pheromone in the regulation of division of labour among adult workers. Bees in colonies receiving brood pheromone initiated foraging at significantly older ages than did bees in control colonies in five out of five trials. Laboratory and additional field tests also showed that exposure to brood pheromone significantly depressed blood titres of juvenile hormone. Brood pheromone exerted more consistent effects on age at first foraging than on juvenile hormone, suggesting that the primer effects of this pheromone may occur via other, unknown, mechanisms besides juvenile hormone. These results bring the number of social factors known to influence honeybee division of labour to three: worker-worker interactions, queen mandibular pheromone and brood pheromone. PMID- 11209887 TI - Convergent evolution of worker policing by egg eating in the honeybee and common wasp. AB - Mutual policing, where group members suppress each others' reproduction, is hypothesized to be important in the origin and stabilization of biological complexity. Mutual policing among workers in social insects can reduce within colony conflict. However, there are few examples. We tested for worker policing in the common wasp Vespula vulgaris. Workers rapidly removed worker-laid eggs but left most queen-laid eggs (four out of 120 worker eggs versus 106 out of 120 queen eggs remained after 1h). Ovary dissection (1150 workers from six colonies) revealed that a small but significant number of workers have active ovaries (4%) equivalent to approximately five to 25 workers per colony. Consistent with effective policing of worker reproduction, microsatellite analysis of males (270 individuals from nine colonies) detected no workers' sons. Worker policing by egg eating has convergently evolved in the common wasp and the honeybee suggesting that worker policing may have broad significance in social evolution. Unlike the honeybee, relatedness patterns in V. vulgaris do not explain selection for policing. Genetic analysis (340 workers in 17 nests) revealed that workers are equally related to the queen's and other workers' sons (worker-worker relatedness was 0.51 +/- 0.04, 95% confidence interval). Worker policing in V. vulgaris may be selected due to the colony-level benefit of conflict suppression. PMID- 11209888 TI - Male contributions to egg production: the role of accessory gland products and sperm in Drosophila melanogaster. AB - Drosophila melanogatser seminal fluid components, accessory gland proteins (Acps) and sperm, induce females to deposit high numbers of fertilized eggs for about 11 days. This high and sustained level of egg deposition requires that oogenesis be stimulated to provide the necessary mature oocytes. To investigate the relative timing and contributions of Acps and sperm in the egg-production process, we examined the rates of oogenic progression and egg deposition in females mated to genetically altered males that have seminal fluid deficient in Acps and/or sperm, and subjected these data to path analysis. We found that Acps and sperm are complementary stimuli necessary for inducing high rates of oogenic progression and rapid egg deposition. While egg deposition and oogenic progression can be induced by Acps alone, both Acps and sperm are required for maximum stimulation of oogenic progression and egg deposition immediately after mating. PMID- 11209889 TI - Indirect partner choice through manipulation of male behaviour by female fowl, Gallus gallus domesticus. AB - The direct and indirect consequences of female copulatory behaviour for copulation success have seldom been quantified. In feral fowl, most copulations were forced by males and copulation success was determined by two factors. First, female differential resistance and solicitation directly affected copulation success and were displayed non-randomly with respect to male social status. Second, another female copulatory behaviour, the distress call, had an indirect effect on both copulation success and the quality of copulation partners. Distress calls triggered male attention to a copulation, which increased the probability of higher-ranking males than the copulating male disrupting the copulation and inseminating the calling female. Females preferentially uttered distress calls when mounted by low-ranking males. Both copulation resistance and distress calling influenced copulation success, but only distress calling increased the probability of copulation disruption by other males. Consistent with the effect of direct selection, differential distress calling indirectly biased copulation success in favour of dominant males. Female fowl may thus ameliorate the effect of male sexual coercion by manipulating male behaviour. PMID- 11209890 TI - The evolution of cooperative breeding through group augmentation. AB - Some individuals (helpers) in cooperatively breeding species provide alloparental care and often suppress their own reproduction. Kin selection is clearly an important explanation for such behaviour, but a possible alternative is group augmentation where individuals survive or reproduce better in large groups and where it therefore pays to recruit new members to the group. The evolutionary stability of group augmentation is currently disputed. We model evolutionarily stable helping strategies by following the dynamics of social groups with varying degrees of subordinate help. We also distinguish between passive augmentation, where a group member benefits from the mere presence of others, and active augmentation, where their presence as such is neutral or harmful, but where helping to recruit new group members may still be beneficial if they in turn actively provide help for the current reproductives ('delayed reciprocity'). The results show that group augmentation (either passive or active) can be evolutionarily stable and explain costly helping by non-reproductive subordinates, either alone or leading to elevated help levels when acting in concert with kin selection. Group augmentation can thus potentially explain the weak relationships between relatedness and helping behaviour that are observed in some cooperatively breeding species. In some cases, the superior mutualistic performance of cooperatively behaving groups can generate an incentive to stay and help which is strong enough to make ecological constraints unnecessary for explaining the stability of cooperatively breeding groups. PMID- 11209891 TI - The ontogeny of the homing pigeon navigational map: evidence for a sensitive learning period. AB - Homing pigeons can learn a navigational map by relying on the heterogeneous distribution of atmospheric odours in the environment. To test whether there might be a sensitive period for learning an olfactory-based navigational map, we maintained a group of young pigeons in an aviary screened from the winds until the age of three to four months post-fledging. Subsequently, the screens were removed and the pigeons were exposed to the winds and the environmental odours they carry for three months. One control group of pigeons was held in a similar aviary but exposed to the winds immediately upon Hedging, while another control group of pigeons was allowed free-flight. When the pigeons from the three groups were released from two distant release sites at about six months of age post fledging, the two control groups were found to be equally good at orientating and returning home, while the experimental pigeons held in the shielded aviary for the first three months post-fledging were unable to orientate homeward and they were generally unsuccessful in returning home. This result supports the hypothesis that environmental experience during the first three months post fledging is critical for some aspect of navigational map learning and that navigational map learning displays sensitive period-like properties. PMID- 11209892 TI - Heritability of arrival date in a migratory bird. AB - The behaviour of long-distance migratory birds is assumed to partly be under the influence of genes, as demonstrated by selection experiments. Furthermore, competition for early arrival among males may lead to condition-dependent migration associated with fitness benefits of early arrival achieved by individuals in prime condition. Here I present field data on the repeatability and the heritability of arrival date in a trans-equatorial migratory bird, the barn swallow Hirundo rustica, and I test for a genetic correlation between arrival date and the expression of a condition-dependent secondary sexual character. The repeatability was statistically significant and the heritability of arrival date was estimated to be 0.54 (s.e. = 0.15). There was no significant evidence of this estimate being inflated by environmental or maternal condition during rearing. Arrival date and migration are condition dependent in the barn swallow, with males with the most exaggerated secondary sexual characters also arriving the earliest. There was a significant genetic correlation between arrival date and tail length in male barn swallows, providing indirect evidence for a genetic basis of this condition dependence. Given the high level of heritability, arrival date could readily respond to selection caused by environmental change. PMID- 11209893 TI - The effects of testosterone on a viral infection in greenfinches (Carduelis chloris): an experimental test of the immunocompetence-handicap hypothesis. AB - The immunocompetence-handicap hypothesis suggests that the honesty of quality signals could be guaranteed if testosterone (T) suppresses immune function while enhancing male ornaments. In addition, it has been proposed that the cost of enhancing ornaments should be highest for males with small ornaments. Recently, the assertion that T causes obligate immunosuppression has been questioned. In this study, we tested whether elevated T levels would increase susceptibility to a viral infection, and whether this hypothesized effect would be most pronounced in males with small ornaments. We surgically inserted T implants into 15 male greenfinches (Carduelis chloris) and control implants into a further 15 males. All birds were then infected with a naturally occurring virus (Sindbis virus, Alphavirus genus), and each bird's daily viraemia (blood virus concentration) was measured for seven days. The specific antibody response was measured for eight weeks. T-implanted males did not exhibit increased viraemia or decreased antibody response, and males with small and large ornaments did not respond differently to T implantation. We did, however, find that T implantation decreased viraemia early in the course of the infection and increased viraemia late in the infection. Thus, our results demonstrate that T may act both to increase and to decrease viraemia. PMID- 11209895 TI - High-performance liquid chromatographic separation of enantiomers of synthetic amino acids on a ristocetin A chiral stationary phase. AB - A macrocyclic glycopeptide, ristocetin A, was used as chiral stationary phase for the high-performance liquid chromatographic separation of enantiomers of 28 unnatural amino acids, such as analogues of phenylalanine, tyrosine and tryptophan, and analogues containing 1,2,3,4-tetrahydroisoquinoline, tetraline or 1,2,3,4-tetrahydro-2-carboline skeletons. Excellent resolutions were achieved for most of the investigated compounds by using reversed-phase or a new polar-organic mobile phase system. The conditions of separation were optimized by variation of the mobile phase composition, temperature and flow-rate. PMID- 11209894 TI - Long-distance interactions in Cyclopean vision. AB - We report on evidence for selective long-distance interactions in Cyclopean binocular vision. When presented with a pair of Cyclopean test bars observers could discriminate trial-to-trial uncorrelated variations in the mean orientation, orientation difference, separation and mean location of the test bars while ignoring random variations in the orientation, width and location of a third bar placed between the two test bars. We propose that the human visual system contains Cyclopean long-distance comparators (i) that compare the outputs of two narrow receptive fields some distance apart while being insensitive to stimuli located between those receptive fields, and (ii) the outputs of which carry orthogonally labelled indicators of orientation difference, mean orientation, separation and mean location. In the evolutionary context, one role for the proposed mechanisms might be to encode information about the silhouettes of animals whose camouflage is broken by the binocular vision of predators. PMID- 11209896 TI - Separation of tanshinones from Salvia miltiorrhiza Bunge by high-speed counter current chromatography using stepwise elution. AB - High-speed counter-current chromatography (HSCCC) was successfully used for isolation and purification of tanshinones from the roots of Salvia miltiorrhiza Bunge by stepwise elution. A set of three solvent systems and other experimental conditions were determined by analytical HSCCC. Using the optimized conditions, the preparative HSCCC separation was performed on 50 mg of crude light petroleum extract yielding pure tanshinones of tanshinone HA (7 mg), tanshinone I (3 mg) and cryptotanshinone (4 mg) all at purities of over 95% in a single run. PMID- 11209897 TI - Analysis of carbohydrates in drinks by high-performance liquid chromatography with a dynamically modified amino column and evaporative light scattering detection. AB - A high-performance liquid chromatographic method with a dynamically modified amino column and evaporative light-scattering detector (ELSD) was established for the direct analysis of the carbohydrates in some drinks. A separation column (Zorbax Rx-SIL, 250 mm x 4.6 mm I.D., 5 microm, Hewlett-Packard, USA) which was modified by ethylenediamine and a guard column (Zorbax Rx-SIL, 12.5 mm x 4.6 mm I.D., 5 microm) were used. The mobile phase was a mixture of water-acetonitrile (1:2.6, v/v) containing 0.03% (v/v) ethylenediamine. Regression equations revealed linear relationship (correlation coefficients=0.996-0.999) between the mass of carbohydrates injected and the carbohydrates peak areas detected by ELSD. The detection limits of ELSD (S/N=3) were between 0.2 and 1.2 microg for different carbohydrates. This method is simple and sensitive. PMID- 11209898 TI - Fast enantioseparations of basic analytes by high-performance liquid chromatography using cellulose tris(3,5-dimethylphenylcarbamate)-coated zirconia stationary phases. AB - In this work, we study the influence of the mobile phase and column temperature on the enantioresolution of basic compounds on microparticulate porous zirconia coated with cellulose tris(3,5-dimethylphenylcarbamate) (CDMPC). The chiral analytes are amino compounds, including a number of beta-blockers. Analytes are eluted with hexane-alcohol mobile phases. We investigated the effect of alcohol (type and concentration), basic eluent additives, and column temperature on the parameters that control resolution (column efficiency, retention and selectivity). Conditions for achieving an adequate separation in the least time have been determined for numerous racemic mixtures. For most solutes, baseline resolution of the enantiomeric pair was achieved in less than 1 min; 12 of 13 pairs were separated in less than 2 min. PMID- 11209899 TI - Direct characterization of isoquinoline alkaloids in a crude plant extract by ion pair liquid chromatography-electrospray ionization tandem mass spectrometry: example of Eschscholtzia californica. AB - An ion-pair HPLC-ESI-MS-MS method has been developed for the direct and rapid characterization of isoquinoline alkaloids in a crudely purified extract of the aerial parts of Eschscholtzia californica (Papaveraceae). This plant was chosen because of its increasing use in pharmaceutical industries and because its well known alkaloid composition allows the optimization of the experimental procedure through an on-line analytical sequence. Thus, 14 isoquinoline alkaloids of different types were detected and characterized. The identities of these compounds were confirmed unambigously by their fragmentation and UV spectra obtained by LC-diode-array detection. Various experiments including tandem mass spectrometry and in-orifice collision induced dissociation were performed and prove that MS-MS is a very efficient technique to identify these compounds. An explanation for each isoquinoline alkaloid type MS-MS fragmentation pattern is proposed and indicates similar neutral and/or radical losses. The order of the fragmentation depended on the type of compound but the lost fragments were similar. PMID- 11209900 TI - Micelle-mediated extraction and preconcentration of ginsenosides from Chinese herbal medicine. AB - The feasibility of employing micelle-mediated extraction as an alternative and effective method for the solubilization, purification and/or preconcentration of active ingredients from herbal products is demonstrated for the first time using the root of American ginseng as a model. When compared to methanol and water, an aqueous surfactant solution containing 10% Triton X-100 yielded faster kinetics and higher recovery for the extraction of various ginsenosides. An experimental design approach (uniform design) was demonstrated as a novel and useful method for the optimization of experimental factors involved in the micelle-mediated extraction process. For the preconcentration of ginsenosides prior to chromatographic determination, a salting-out agent (sodium sulfate) was employed to make the efficient cloud point extraction of both hydrophobic and hydrophilic ginsenosides into the surfactant-rich phase possible, as well as to increase the preconcentration factor by reducing the volume of the surfactant-rich phase. PMID- 11209901 TI - Pressurized liquid extraction of berberine and aristolochic acids in medicinal plants. AB - Berberine and aristolochic acids I and II present naturally in medicinal plants were extracted using a laboratory-made pressurized liquid extraction (PLE) system in the dynamic mode. As the target analytes were present naturally in the medicinal plants, spiking was not done and comparison with ultrasonic extraction and Soxhlet extraction was performed to assess the method accuracy. The effect of temperature, volume of solvent required and particle size were investigated. Method precision (RSD, n=5) between 1.98 and 3.4% was achieved for the extraction of berberine and aristolochic acids I and II in medicinal plants and lower than 8% for lower levels of aristolochic acid II in medicinal plants. PMID- 11209902 TI - Determination of nonylphenol ethoxylate oligomers by liquid chromatography electrospray mass spectrometry in river water and non-ionic surfactants. AB - Liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) for the quantitative determination of five nonylphenol ethoxylate (NPE) oligomers in river water was described. These NPE oligomers were separated on a poly(vinyl alcohol) gel column using acetonitrile-30 mM ammonium acetate as the mobile phase followed by ESI-MS detection without any sample concentration steps. The sample was only filtered using the disposable filter and the aliquot (100 micro1) of this sample was injected into the LC-ESI-MS system. All NPE oligomers were detected using the [M+NH4]-ion. Detection limits ranged from 160 pg/ml (NPE4) to 240 pg/ml (NPE2), repeatability and reproducibility ranged from 4.2% (NPE2) to 6.2% (NPE6) and from 7.4% (NPE5) to 9.8% (NPE6). PMID- 11209903 TI - Gas chromatography for in situ analysis of a cometary nucleus. II. Analysis of permanent gases and light hydrocarbons with a carbon molecular sieve porous layer open tubular column. AB - Considering the severe constraints of space instrumentation, a great improvement for the in situ gas chromatographic (GC) determination of permanent and noble gases in a cometary nucleus is the use of a new carbon molecular sieve porous layer open tubular (PLOT) column called Carbobond. No exhaustive data dealing with this column being available, studies were carried out to entirely characterize its analytical performances, especially when used under the operating conditions of the cometary sampling and composition (COSAC) experiment of the European Space Agency (ESA) Rosetta space mission to be launched in 2003 for a rendezvous with comet 46 P/Wirtanen in 2011. The high efficiency and speed of analysis of this column at both atmospheric and vacuum outlet column pressure is demonstrated, and the kinetic mass transfer contribution of this carbon molecular sieve adsorbent is calculated. Besides, differential adsorption enthalpies of several gases and light hydrocarbons were determined from the variation of retention volume with temperature. The data indicate close adsorption behaviors on the Carbobond porous layer adsorbent and on the carbon molecular sieve Carboxen support used to prepare the packed columns. Moreover, taking into account the in situ operating conditions of the experiment, a study of two columns with different porous layer thicknesses allowed one to optimize the separation of the target components and to select the column parameters compatible with the instrument constraints. Comparison with columns of similar selectivity shows that these capillary columns are the first ones able to perform the same work as the packed and micro-packed columns dedicated to the separation of this range of compounds in GC space exploration. PMID- 11209904 TI - Identification of impurities affecting commercial ethylene glycol UV transmittance. AB - As a raw material for making polyesters, ethylene glycol has a special specification of UV transmittance. At present, ethylene glycol produced by some plants still has low UV transmittance rendering it unsuitable for use in polyester production. In this paper, a method was developed for the identification of the impurities that cause commercial ethylene glycol to have low UV transmittance, using solid-phase extraction (SPE) and some analytical techniques such as high-performance liquid chromatography, gas chromatography mass spectrometry and gas chromatography-Fourier transform infrared spectroscopy. The major UV-absorbing impurities were identified as some alkyl homologues of 2 hydroxycyclopent-2-en-1-one, including 2-hydroxy-3,5-dimethylcyclopent-2-en-1 one, 2-hydroxy-3-methylcyclopent-2-en-1-one, 2-hydroxy-3,4-dimethylcyclopent-2-en 1-one, 2-hydroxy-3-ethyl-4-methylcyclopent-2-en-1-one and 2-hydroxy-3 ethylcyclopent-2-en-1-one. Their concentrations were estimated to be less than 2 microg ml(-1). It is believed that with the above results, ethylene glycol producing plants might make process improvements to remove these impurities more effectively and more easily. PMID- 11209905 TI - Resolution of positional isomers by capillary electrochromatography. AB - Electroseparations have been very successful in increasing efficiencies and reducing analysis times. The analytical technique originally applied to open tube capillaries (capillary electrophoresis) has been used as a basis to develop renewed interest in electrochromatography. This paper describes the use of capillary electrochromatography to separate two positional isomers and describes a comparison between gas chromatography (GC), capillary electrochromatography (CEC) and nano-HPLC. The resolution of these isomers is quite crucial, since one of the isomers is the impurity in a pharmaceutically active drug. PMID- 11209906 TI - 2000: the drug problem in the European Union. PMID- 11209907 TI - Controversy--water fluoridation. PMID- 11209909 TI - Medical school entry. PMID- 11209908 TI - Water fluoridation: safe and effective. PMID- 11209911 TI - Undetected hyperglycaemia among hospital in-patients. AB - To assess the prevalence of previously undiagnosed hyperglycaemia consistent with a diagnosis of Diabetes Mellitus in a consecutive series of hospital in-patients. Retrospective case note review. University Teaching Hospital. 800 consecutive hospitalised patients aged over 50 years. The main outcome measures the prevalence of hyperglycaemia [corrected]. We searched the biochemistry laboratory computerised database for results of all biochemistry tests carried out during each patient's admission. The medical records of those with at least one plasma glucose value in the hyperglycaemic range (glucose > or =11.1 mmol/l and/or > or =7.0 mmol/l on casual and/or fasting measurements respectively) were reviewed by two observers using a standardised method and a check list for data collection. PMID- 11209910 TI - The current epidemiology of SIDS in Ireland. AB - This paper examines some epidemiological factors associated with SIDS to give a general profile of SIDS cases occurring in Ireland between the years 1993 to 1997. There has been a dramatic decrease in the incidence of the Sudden Infant Death Syndrome (SIDS) in the Republic of Ireland in the last decade from an average rate of 2.2/1000 live-births in the 1980s to 0.8/1000 live-births in the years 1993-1997, a decrease of 100 deaths a year. The fall in the SIDS rate has been seen in many countries and is felt to be associated with Reduce The Risks (RTR) of SIDS campaigns and the avoidance of the prone sleeping position. The use of the prone sleep position averaged at 6% of children being put prone in the years 1993-1997 but the prone position has progressively decreased from 13% of children being put prone in 1994 to only 2% in 1997. The profile of the Irish SIDS cases is similar to that of SIDS cases in other countries following similar RTR campaigns with a male predominance, the characteristic clustering of deaths in the first six months of life and the majority of cases (75%) occuring in the night sleep period. The loss of the seasonal variation of the time of death is also shown and factors such as lower socio-economic status, unemployment and medical card eligibility were seen in higher proportions in SIDS families than in the general population. A high percentage of SIDS mothers smoked (73%). Higher smoking rates were seen among younger and single mothers and smoking rates were inversely related to educational level and socioeconomic grouping. An urgent question that needs to be addressed is how socioeconomic disadvantage increases the SIDS risk and what factors influence socioeconomically disadvantaged families to adopt life style and parenting practices such as smoking that influence their children's health. PMID- 11209912 TI - Smoking and quitting among Irish teenage males. AB - Nicotine addiction in adulthood is usually preceded by exposure to cigarettes in adolescence. A minimal exposure may be sufficient to produce addiction. Strategies to reduce adult smoking must address those factors, which influence teenage smoking. In this study we aimed to establish the prevalence of smoking in male secondary schools, to measure the association between student's smoking status and parental, peer and sibling smoking and to describe attempted quitting. An anonymous questionnaire was given to 1070 male secondary school pupils in two schools in County Louth. Twenty-seven percent of respondents smoked every day or on most days. Having a best friend who smoked was associated with personal smoking (O.R. 11.75, C.I. 8.6-16.08) as was sibling smoking (O.R. 3.49, C.I. 2.67 4.57.) Seventy percent of smokers stated that they wanted to stop and 75% that they had tried to stop. Only five smokers (1.2%) had been advised to quit by their general practitioner. We conclude that smoking is as prevalent among teenage boys in Ireland as it has been shown to be elsewhere and that most teenagers are unable rather than unwilling to stop. PMID- 11209913 TI - Rotavirus gastroenteritis among paediatric patients at Tralee general hospital. AB - Rotavirus infection among paediatric patients in Tralee general hospital was monitored over 4 years (1994 - 1998). A total of 2,319 specimens from gastroenteritis patients less than 7 years old were tested by latex agglutination assay, of which 203 (8.75%) were deemed positive. An inverse correlation was observed between age and susceptibility to infection, with the very young (under 2 years) most frequently infected. The virus was almost equally distributed among males (53%) and females (47%) testing positive for rotavirus. A distinctive early Spring peak of infection was evident annually, although the largest peak was identified in December 1997. This correlated with a significant change in circulating genotype as determined by RT-PCR based genotyping analysis of 45 rotavirus samples. In 1997, rotavirus accounted for 64% of all identified paediatric enteric agents at Tralee General for which an infectious agent could be identified. The average hospital stay was 3.2 days, and the direct hospital costs for rotavirus associated gastroenteritis was estimated at pounds sterling 31,232 per annum. PMID- 11209914 TI - "Saves" project. PMID- 11209915 TI - To push or not to push--a personal experience. PMID- 11209916 TI - How do General Practitioners learn of their patient's deaths? AB - OBJECTIVES: To investigate the methods by which General Practitioners learn, or do not learn, of their patients deaths, when the deaths occur in an institution in which the General Practitioner has no direct role in their care. DESIGN: Using a semi-structured telephone questionnaire the relevant General Practitioners were asked of the method, if any, by which they had learned of their patients deaths, and their views on this. SETTING: Sligo, Ireland. RESULTS: In 6 (16%) of the 37 cases, the GP was informed of the death within one working day by hospital staff. In 22 (59%) of the cases, the GP had learned of the death through other means. In 9 (26%) of the cases the GP had not learned of the death. In 28 (75%) of the cases, the GPs were dissatisfied with either the fact that they did not know of the death, or even if they did know, the method by which they learned of the patients death. CONCLUSION: General Practitioners, for a variety of reasons, wish to learn of their patient's deaths within a short length of time of such deaths occurring. When deaths occur in an institution in which the GP has no direct role in the care of their patients, the information is not forwarded to the GP within a reasonable length of time in the vast majority of cases. Such institutions need to realise the importance of this simple act, and to make it routine to forward the information. PMID- 11209917 TI - Prophylaxis in RSV infection (Palivizumab)--is it worthwhile? AB - Respiratory syncytial virus (RSV) is a recognised cause of lower respiratory tract infection in infants and young children. It causes severe respiratory disease in preterm infants with or without chronic lung disease. This study, conducted at Waterford Regional Hospital, evaluates the incidence of RSV infection in hospitalised children, its seasonal variation, and effectiveness of its prevention. Thirty eight percent of admitted children with bronchiolitis were RSV positive in the year 1999 November to March is the peak season for this infection. A highly selected group of 7 preterm children with or without chronic lung disease received Palivizumab prophylaxis. Not one of them acquired RSV infection. The high cost of Palivizumab was the main factor for its restricted use. Palivizumab was found to be effective in preventing RSV infection in our study. Since we had a small number of patients, further studies are needed for its economic and judicious use. Respiratory syncytial virus (RSV) is virulent easily transmissible and the most common cause of lower respiratory tract disease in children of less than 2 years of age. Up to 98% of children attending day care will be infected in single RSV season. Between 0.5% and 3.2% of children with RSV infection require Hospitalisation. Approximately 90,000 hospital admissions and 4500 deaths per year were reported in United States. In Ireland 2807 patients were admitted with Bronchiolitis in 1998. Major risk factors for hospitalisation due to RSV are Prematurity, chronic lung disease, congenital heart disease, compromised immunity and age younger then 6 weeks in otherwise healthy children. No effective treatment of RSV positive bronchiolitis beside supportive care in the form of adequate nutrition and oxygen therapy is available. Antiviral therapies such as Ribavirin has not been proved to be effective in RSV infection. Bronchodilators show variable results. Corticosteroids were not found effective. There is no effective vaccine available as yet. There is no proven method for active immunity. Various immunoglobulins are available for acquiring passive immunity against RSV infection. PREVENT study group in Jan. 1997 showed intravenous immunoglobulin (RSV- IGIV) use in reducing 41% to 63% hospitalisation in RSV patients. But RSV-IGIV was not licensed outside the United States because of risk of transmission of blood borne products, difficulty in administration ie. intravenous access, large fluid volume (15 ml/kg), high protein load (750 mg/kg), shortage of supply and need to postpone live vaccine (eg. MMR, varicella). monoclonal antibody Palivizumab was developed for prophylaxis against RSV infection. Clinical safety and efficacy of Palivizumab were demonstrated in IMpact trial published in Sept. 1998. Reduction in hospitalisation up to 55% was noted in this study. It was a pivotal randomised, double blind, placebo controlled phase 3 study conducted in 139 centres throughout Canada, United States and United Kingdom. We looked at our experience in patients admitted with bronchiolitis in Waterford Regional Hospital. We described the outcome of carefully selected Seven children of high risk group for Palivizumab prophylaxis. Its clinical Implications and cost effectiveness was evaluated in this study. PMID- 11209918 TI - Natriuretic peptides inhibit apoptosis and prolong the survival of serum-deprived PC12 cells. AB - Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were investigated to determine effects on apoptotic DNA fragmentation and survival in serum-deprived PC12 cells. Both peptides caused prolonged cGMP (but not cAMP) elevations lasting for > or = 6 h. The cGMP elevations were 10-, 50- and 68-fold for ANP and 26-, 100- and 148-fold for BNP at 1, 10 and 100 nM, respectively. BNP caused dose-dependent increases in cell survival rates during 3 days of serum deprivation. BNP (1 nM) increased 24 h survival rate from 36% to 67%. ANP (1 nM), BNP (1 nM) and 8-bromo-cGMP (0.1 mM) inhibited by 74.8%, 46.7% and 86.8%, respectively, the apoptotic DNA fragmentation in serum-deprived PC12 cells, measured by our recently developed quantitative technique using capillary electrophoresis with laser-induced fluorescence detector (CE-LIF). The data suggest prolonged cGMP elevations caused by ANP or BNP inhibit apoptotic DNA fragmentation and prolong the survival of serum-deprived PC12 cells. PMID- 11209919 TI - Disappearance of beta2-adrenergic receptors on astrocytes in canine distemper encephalitis: possible implications for the pathogenesis of multiple sclerosis. AB - It has been reported that astrocytes in the white matter of patients with multiple sclerosis (MS) lack beta2-adrenergic receptors. This abnormality might explain why astrocytes in active MS plaques aberrantly express major histocompatibility (MHC) class II molecules, which play an important role in the immunological cascade leading to myelin destruction. Canine distemper (CD) virus primarily infects astrocytes and causes a demyelinating disease in dogs that closely resembles MS. In control dogs, including three dogs with another inflammatory disease, beta2-adrenergic receptor immunoreactivity was observed on both neurons and astrocytes. In dogs with CD encephalitis, beta2-adrenergic receptors were present on neurons, but were absent on astrocytes in acute lesions, demyelinated lesions, and normal-appearing white matter. Similar to MS, several astrocytes in demyelinated lesions expressed MHC class II. These findings suggest that MS and the demyelinating stages of CD encephalitis have a common pathogenetic factor, and that the loss of astrocytic beta2-adrenergic receptors in MS might be induced by a viral infection of astrocytes. PMID- 11209920 TI - Judging semantic and episodic incongruity: a magnetoencephalographic study. AB - Evoked magnetic fields over the entire head were measured during a semantic judgment task, in which conditions of the pre-test learning session were manipulated. Subjects learnt related and unrelated category-noun pairs, and were then asked to judge the relationship between category and noun. Unrelated pairs evoked activation around 400 ms in the left temporal area. In addition, newly presented related pairs, of which the categories were used to learn unrelated pairs, also evoked similar activities. Our findings suggest that these activities are not only related to the semantic incongruity between a pair of words as in previous studies, but also to the episodic incongruity between the learning and measurement sessions. PMID- 11209921 TI - Beta-VLDL protects against A beta(1-42) and apoE toxicity in human SH-SY5Y neuroblastoma cells. AB - The toxic effects of beta-amyloid (A beta) (1-42), apolipoprotein E (apoE) isoforms, and apoE/A beta complexes were studied in human SH-SY5Y neuroblastoma cells and fibroblasts using MTT reduction. In SH-SY5Y cells, A beta(1-42) gave time-dependent toxicity over 2-48 h, which was reduced by co-incubation with rabbit beta-very low density lipoproteins (beta-VLDL). Human recombinant apoE3 and E4 isoforms were also toxic by themselves and also potentiated A beta effects when used alone, but not when associated with beta-VLDL. None of the treatments were toxic to human fibroblasts. These results suggest that beta-VLDL has a protective role on A beta-induced neurotoxicity and that the status of apoE or the conformation of lipoprotein containing apoE particles may be important for determining the contribution of apoE to neurodegeneration. PMID- 11209922 TI - Neuromagnetic evidence for early access to cognitive representations. AB - How do physical and cognitive properties of stimulus words influence the neuromagnetic response of the human brain? Are the physiological correlates of these properties dissociable and at which latencies can they be observed? Short and long words, as well as rare and common words, were repeatedly presented in a memory task while neuromagnetic brain responses were recorded using MEG. Word length and frequency were reflected by brain responses at overlapping but distinct intervals. The influence of the physical factor, length, started at approximately 100 ms after onset of written words, immediately followed by a physiological manifestation of the non-physical cognitive stimulus property, word frequency, which was first apparent at 120-160 ms. There was a differential frequency effect: neurophysiological correlates of short words showed the frequency influence much earlier than did longer words. These data indicate that non-physical cognitive aspects of word stimuli can be reflected in early neuromagnetic responses, and that the latency of these physiological correlates of cognitive stimulus properties may depend on the physical stimulus make-up. PMID- 11209923 TI - Functional connections between the HVC and the shelf of the zebra finch revealed by real-time optical imaging technique. AB - Auditory-motor interaction is essential for the understanding of avian song learning and maintenance. The HVC is thought to be the most important station for auditory-motor integration in the avian song system. However, little is known about where and how auditory inputs are conveyed into the HVC. The shelf, a multi auditory recipient region located along the ventral border of the HVC, is thought to be a possible source of auditory inputs to the HVC. Here, we investigated the functional neural connections between the HVC and surrounding area of the HVC including the shelf in zebra finch brain slices, using the real-time optical recording technique. Unexpectedly electrical stimulation of the shelf region did not induce signal propagation into the HVC, but stimulation within the HVC propagated strong signals into the shelf. These results suggest that the shelf is the region that receives output signals from the HVC, rather than a major source of auditory inputs to the HVC. PMID- 11209924 TI - Event-related potentials and audiovisual stimuli: multimodal interactions. AB - In a discrimination task event-related potentials (ERPs) were recorded in human participants to simultaneously presented visual and auditory stimuli with relevant and irrelevant auditory and visual features. Stimuli consisted of combinations of a sine-wave tone (either target or non-target frequency) and a rectangle of particular (target or non-target) orientation. In two conditions either the auditory or the visual discrimination was easier. Stimuli with just one target feature elicited attention-related ERP components (selection negativity and N2b in the visual, and N2b in the auditory modality) only if that feature could be easily discriminated. This finding shows the hierarchical organization of attentional processing of auditory and visual features. Target stimuli in both conditions elicited visual and auditory attention-related components. This finding, together with the similarity of ERPs to stimuli without target features suggest, that these components cannot be considered as on-line correlates of elementary discrimination processes. PMID- 11209925 TI - Steroids differentially inhibit the nicotinic acetylcholine receptor. AB - The effect of various natural and synthetic steroids on the function of the nicotinic acetylcholine receptor (AChR) was studied at the single-channel level. AChR channel kinetics was affected by some substitutions in the cyclopentaneperhydrophenantrene ring. Functionally relevant substitutions shortened channel open state duration, an effect that varied for different steroids. The presence of a polar group at C11 contributed to the inhibitory potency of the steroid. Among mono-hydroxylated steroids such as 11- and 17-OH progesterone, the highest potency was displayed by the former showing a level similar to that of the reference compound, hydrocortisone. When the effects were analyzed in terms of the octanol-water partition coefficient, a linear relationship was unexpectedly found between the hydrophilicity of the steroids and their inhibitory potency. PMID- 11209926 TI - An actin-binding protein, CAP, is expressed in a subset of rat taste bud cells. AB - Single cell cDNA libraries were constructed from taste bud cells of rat circumvallate papillae. Using three steps of screening, including differential hybridization, sequence analyses and in situ hybridization, a clone encoding a rat homolog of yeast adenylyl cyclase-associated protein (CAP) was identified to be highly expressed in a subset of taste bud cells. PMID- 11209927 TI - Phonological aspects of word recognition as revealed by high-resolution spatio temporal brain mapping. AB - We describe, for the first time, the use of high-resolution event-related brain potentials (hrERP) to identify the spatio-temporal characteristics of neural systems involved in phonological analysis. Subjects studied a visual word/non word that was followed by the brief presentation of a prime letter (e.g. House, M) with the instruction to anticipate the word/non-word formed by replacing the word's first letter with the prime letter. After the prime letter, an auditory target word/non-word was presented that either matched/mismatched expectations (e.g., Mouse/Barn). ERPs were recorded to the onset of the auditory targets and scalp topographical maps were derived for the phonological mismatch negativity (PMN). The PMN reflected phonological analysis and examination of the peak topography revealed that the response was characterized by a prominent frontal, right-asymmetrical distribution. Spatial de-blurring (using current source density maps) indicated that the PMN scalp topography resulted primarily from an active left anterior source. The current results provide the initial evidence for the localization of the intra-cranial generator(s) involved in phonological analysis. PMID- 11209928 TI - Event-related potentials of recognizing happy and neutral faces. AB - In event-related potentials (ERPs) studies, recognition memory is associated with two positivities: one over parietal regions, and one over frontal regions. With nameable neutral stimuli, such as words or common objects, the parietal effect is usually left lateralized, and the frontal effect is usually right lateralized. We investigated the lateralization of these effects for nonnameable emotional stimuli: unfamiliar faces with happy and neutral expressions. The parietal effect was bilateral, suggesting that the left lateralization of this effect in studies using nameable stimuli reflected verbal processing. The frontal effect was left lateralized for happy faces, but right lateralized for neutral faces. This finding is consistent with the valence hypothesis, which posits that processing of pleasant emotions is lateralized to the left hemisphere. PMID- 11209929 TI - Magnetoencephalographic (MEG) localization of the auditory N400m: effects of stimulus duration. AB - The effects of stimulus duration on the elicitation and equivalent current dipole (ECD) localization of the auditory N400(m) were studied in two subject groups, either familiar or unfamiliar with Finnish language, using a sentence-processing paradigm with incongruent ending words of either short or long duration. Long duration words elicited a broad response at around 400 ms, the generator location(s) of which could not be reliably determined using ECD estimation. In contrast, short-duration words elicited a sharp, strong-amplitude response at about 400 ms latency and it's source location could be reliably determined as being in the vicinity of auditory cortex. Subjects unfamiliar with the Finnish language elicited no response at the 400 ms range. Thus, the use of short duration words appears to be an important prerequisite for the elicitation and localization of N400m. The differential amplitude behaviour of the N400m between the two subject groups further suggests that comprehension of the semantic content of the speech message is also required. PMID- 11209931 TI - Immunological identification of the mammalian H3 histamine receptor in the mouse brain. AB - Affinity-purified antibodies raised against the peptide sequence H3 (349-358) receptor specifically recognized two protein species with Mr 62,000 and 93,000 in adult mouse forebrain membranes. Both immunoreactive species were suppressed greatly by preincubation of the antibody with the respective peptide. Immunohistochemical analysis using affinity-purified anti-H3 (349-358) antibodies yielded a high degree of coincidence with ligand-autoradiographical information, with high levels detected in the CA3 and dentate gyrus of the hippocampus, laminae V of the cerebral cortex, the olfactory tubercle, Purkinje cell layer of the cerebellum, substantia nigra, globus pallidus, thalamus and striatum. This study suggests further biochemical evidence for multiple H3 receptor subtypes and the widespread distribution of the H3 receptor in the mammalian brain. PMID- 11209930 TI - Evidence for a modulatory role of Ih on the firing of a subgroup of midbrain dopamine neurons. AB - A previous investigation has suggested that the hyperpolarization-activated cation current Ih does not contribute to the spontaneous firing of midbrain dopaminergic neurons. This conclusion was reached using Cs(-1). We have re examined this question with extracellular recordings in slices using the more specific blocker ZD7288. In two-thirds of the cells, low concentrations of ZD7288 induced a decrease of the spontaneous firing. The maximal inhibition was about 40% and the mean IC50 was 1.6 microM. This effect was probably direct because it persisted in the presence of antagonists of various receptors. These concentrations of ZD7288 had no effect in the remaining one third of the examined cells. However, the highest concentration of ZD7288 (300 microM) abolished the firing of all dopaminergic neurons, probably by a mechanism unrelated to the blockade of Ih. We conclude that Ih controls to a certain extent the firing of a majority of midbrain dopaminergic neurons. PMID- 11209932 TI - Ibogaine alters synaptosomal and glial glutamate release and uptake. AB - Ibogaine has aroused expectations as a potentially innovative medication for drug addiction. It has been proposed that antagonism of the NMDA receptor by ibogaine may be one of the mechanisms underlying its antiaddictive properties; glutamate has also been implicated in ibogaine-induced neurotoxicity. We here report the effects of ibogaine on [3H]glutamate release and uptake in cortical and cerebellar synaptosomes, as well as in cortical astrocyte cultures, from mice and rats. Ibogaine (2-1000 microM) had no effects on glutamate uptake or release by rat synaptosomes. However, ibogaine (500-1000 microM) significantly inhibited the glutamate uptake and stimulated the release of glutamate by cortical (but not cerebellar) synaptosomes of mice. In addition, ibogaine (1000 microM) nearly abolished glutamate uptake by cortical astrocyte cultures from rats and mice. The data provide direct evidence of glutamate involvement in ibogaine-induced neurotoxicity. PMID- 11209933 TI - Preconditioning with spreading depression activates specifically protein kinase Cdelta. AB - Preconditioning with brief ischemia or spreading depression (SD) confers tolerance in cortical neurons to subsequent episode of ischemia. In myocardium a similar preconditioning is achieved by mechanisms, which are mediated by protein kinase C (PKC) alpha, delta, epsilon or zeta isoform. We induced SD by cortical application of KCl in the rat and analyzed cortical tissues after recovery of 30 min, 4 h and 12 h. While no changes at protein levels or activity of PKCalpha, epsilon or zeta were detected, a considerable increase in membrane translocation of PKCdelta was seen at 30 min and 12 h. A significant increase at mRNA level, protein amount and autophosphorylation at 12 h confirmed the late activation of PKCdelta, which may be involved in neuronal protection by preconditioning. PMID- 11209934 TI - LIF is more potent than BDNF in promoting neurite outgrowth of mammalian auditory neurons in vitro. AB - Neurotrophic factors are known to play a crucial role in the elongation and guidance of auditory nerve fibres to their targets within the organ of Corti. Maintenance of these neural connections following deafness would clearly influence the efficacy of therapies for hearing recovery. The growth factors leukaemia inhibitory factor (LIF), brain-derived neurotrophic factor (BDNF) and transforming growth factor-beta 5 (TGF-beta5) were tested for their efficacy in promoting neurite outgrowth from dissociated cultures of early postnatal rat auditory neurons. Our results indicate that while BDNF enhances neurite outgrowth in a strong fashion, LIF is more potent; moreover, the combined administration of both factors has even greater neuritogenic capacities. TGF-beta5, although neurotrophic, has no neuritogenic activity on cultured auditory neurons. LIF and BDNF may therefore be potential candidates when developing pharmacological therapies for hearing recovery. PMID- 11209935 TI - Transport of endosomal early antigen 1 in the rat sciatic nerve and location in cultured neurons. AB - Early endosomal antigen 1 (EEA1) is known to be a marker of early endosomes and in cultured hippocampal neurons it preferentially localizes to the dendritic but not the axonal compartment. We show in cultured dorsal root ganglia and superior cervical ganglia neurons that EEA1 localizes to the cell bodies and the neurites of both sensory and sympathetic neurons. We then show in vivo using a ligated rat sciatic nerve that EEA1 significantly accumulates on the proximal side and not on the distal side of the ligation. This suggests that EEA1 is transported in the anterograde direction in axons either as part of the homeostatic process or to the nerve ligation site in response to nerve injury. PMID- 11209936 TI - Olfactory centres in Alzheimer's disease: olfactory bulb is involved in early Braak's stages. AB - In Alzheimer's disease (AD), neurofibrillary tangles spread from the entorhinal cortex to the limbic system, then to neocortical areas, according to the Braak's stages. Olfaction is impaired in early stages of AD. The aim of this study was to describe the pathology of the cortical olfactory centres in relation to Braak's stages determining the earliest site of pathology. We examined 15 control and 15 AD cases. The primary olfactory cortices were involved in more advanced Braak's stages, while olfactory bulbs were damaged in very early (i.e. Braak's stage 0 or 1) stages. These results are supporting the fact that olfaction might be an early marker in AD and argues against the hypothesis that AD pathology is spreading through the olfactory system. PMID- 11209937 TI - Complement anaphylatoxin C3a is selectively protective against NMDA-induced neuronal cell death. AB - The anaphylatoxin C3a is a potent inflammatory polypeptide released at sites of complement activation. To test whether C3a might alter neuronal outcome following an ischemic insult, we determined the effects of purified human C3a on murine primary cortical cell cultures exposed to apoptotic or excitotoxic paradigms. C3a prevented neither serum deprivation-induced apoptotic neuronal death, nor AMPA/kainate-mediated excitotoxicity. However, in mixed cultures of neurons and astrocytes, C3a dose-dependently protected neurons against NMDA toxicity (47% neuroprotection using 100 nM C3a, p < 0.01, n = 12). The neuroprotective effect of C3a was observable only in the presence of astrocytes. These observations suggest that C3a is involved in excitotoxicity-mediated neuronal death through astrocyte stimulation and extend its role beyond immune functions. PMID- 11209938 TI - The effects of propofol on NMDA- or nitric oxide-mediated neurotoxicity in vitro. AB - Acute brain ischemia causes neurotoxic cascades including NMDA receptors and NO. Propofol, an i.v. anesthetic, is thought to have a neuroprotective effect. We investigated the influence of propofol on NMDA/NO neurotoxicity using Shibuta's established model of primary brain cultures. Cortical neurons prepared from E16 were used after 13-14 days in culture. The neurons were exposed to various concentrations of propofol with NMDA or NO-donor. The survival rates of neurons exposed to 30 microM NMDA with or without 300 microM propofol were 12.1 +/- 2.2% and 11.9 +/- 2.2%, respectively. The survival rates exposed to 30 microM NO-donor with or without 300 microM propofol were 11.2 +/- 4.2% and 14.0 +/- 3.9%, respectively. These results suggest that neuroprotective effect of propofol is limited and propofol does not offer advantages over thiopental against NMDA/NO induced cytotoxicity. PMID- 11209939 TI - Disrupted neural responses to phonological and orthographic processing in dyslexic children: an fMRI study. AB - Developmental dyslexia, characterized by difficulty in reading, has been associated with phonological and orthographic processing deficits. fMRI was performed on dyslexic and normal-reading children (8-12 years old) during phonological and orthographic tasks of rhyming and matching visually presented letter pairs. During letter rhyming, both normal and dyslexic reading children had activity in left frontal brain regions, whereas only normal-reading children had activity in left temporo-parietal cortex. During letter matching, normal reading children showed activity throughout extrastriate cortex, especially in occipito-parietal regions, whereas dyslexic children had little activity in extrastriate cortex during this task. These results indicate dyslexia may be characterized in childhood by disruptions in the neural bases of both phonological and orthographic processes important for reading. PMID- 11209940 TI - MRI of subacute hemorrhagic transformation in the rat suture occlusion model. AB - In this study we investigated the utility of different MRI techniques for the detection and predictability of hemorrhagic transformation (HT) in a rat model of transient focal cerebral ischemia. Hemorrhagic infarction was reliably identified with gradient-echo sequences and developed between 2 and 7 days following the insult. None of the investigated early MRI features of the ischemic lesions (including the apparent diffusion coefficient and post-reperfusion blood-brain barrier damage) was a good predictor of HT severity at 7 days. This indicates that subacute HT at 2-7 days occurs independently of the severity of acute tissue and BBB damage. PMID- 11209941 TI - Time estimation in schizophrenia: an fMRI study at adjusted levels of difficulty. AB - fMRI was performed in nine male schizophrenia patients and 15 healthy male controls during an auditory time estimation (timing), a frequency (i.e. pitch) discrimination task, and rest. An adaptive psychophysical approach, the weighted up-down method, was used to adjust individual performance to a level of 75% probability for correct answers. Although performing on the same level of individual difficulty, schizophrenia patients revealed less activations in prefrontal cortex and caudate nucleus, comparing time vs rest. Timing specific differences (i.e. timing vs pitch) between patients and controls were found in the posterior putamen, anterior thalamus, and right medial prefrontal cortex, with patients showing relative hypoactivity. Impairment in time estimation in schizophrenia might be mediated by specific fronto-thalamo-striatal dysfunction. PMID- 11209943 TI - Chromosomal mapping and organization of the human histamine H3 receptor gene. AB - The histamine H3 receptor (H3R) was recently cloned, and two isoforms, termed H3L and H3S, differing in the third intracytosolic loop, were isolated but the chromosomal mapping and organization of its gene remained unknown. PCR analysis of a human x rodent cell hybrid panel indicated that the H3R gene is located in the telomeric region of chromosome 20q. Alignment of human H3R cDNA sequences with DNA sequences of this chromosome revealed that its coding region comprises three exons interrupted by two introns located in the second transmembrane domain (TM2) and second intracytosolic loop, respectively. Thus the organization of the H3R gene indicates that the H3L and H3S isoforms, that we characterized not only in rodents but also in humans, are generated by retention and deletion, respectively, of a pseudo-intron located in the third intracytosolic loop. PMID- 11209942 TI - Intrathecal administration of PNA targeting galanin receptor reduces galanin mediated inhibitory effect in the rat spinal cord. AB - Peptide nucleic acids (PNA) are nucleic acid analogues containing neutral amide backbone, forming stable and tight complexes with complementary DNA/RNA. However, it is unclear whether unmodified PNA can efficiently penetrate neuronal tissue in order to act as antisense reagent. Here we show that intrathecal (i.t.) injection of an unmodified antisense PNA complementary to the rat galanin receptor type 1 (GalR1) mRNA is able to block the inhibitory effect of i.t. administered galanin on spinal nociceptive transmission. Autoradiographic ligand binding studies using [125I]galanin show that the unmodified PNA is able to reduce the density of galanin binding sites in the dorsal horn. Thus, unmodified PNA applied i.t. appears to function as an effective antisense reagent in rat spinal cord in vivo. PMID- 11209944 TI - Satiety threshold during maintained cocaine self-administration in outbred mice. AB - Male Swiss Webster mice maintained cocaine self-administration in a regular and dose-dependent manner. These characteristics made it possible to apply the satiety threshold model of drug self-administration developed recently for cocaine self-administration in rats. Non-linear regression analysis revealed that cocaine satiety threshold was 1.3 +/- 0.6 mg/kg and the functional half-life of the cocaine was 8.1 +/- 2.2 min. Whether the self-administration of cocaine was maintained by lever presses or nose pokes did not influence the inter-injection intervals. The results are consistent with the pharmacological model of maintained cocaine self-administration. The ability to determine addiction relevant phenotypes (the satiety threshold and functional half-life of cocaine) in inbred strains of mice may help to identify the genetic determinants of cocaine self-administration behavior. PMID- 11209945 TI - Coordinated expression of Hoxa2, Hoxd1 and Pax6 in the developing diencephalon. AB - Coordinated expression of Hoxa2, Hoxd1 and Pax6 proteins were found to coincide with the three developmental stages of the diencephalon, as described for the mouse brain. In the first stage (embryonic day (E) 10-12) Hoxa2, Hoxd1 and Pax6 (an early marker gene of the diencephalon) were expressed as early as E10.5 in prosomeres (p), p2 and p3. All three proteins continue to exhibit overlapping domains of expression at E12.5-13 (beginning of the second stage) when the primitive dense cell layer begins to differentiate into the internal germinal, external germinal and mantle layers. Towards the end of the second stage (E15), Pax6 expression was down-regulated whereas Hoxa2 and Hoxd1 continued to exhibit overlapping domains of expression for both protein and mRNA. Hoxd1 expression decreased significantly in the third stage of diencephalic development (E16 postnatal) such that only Hoxa2 expression persisted in the diencephalon of newborn mice. The temporal and spatial expression of these three proteins imply that coordinated waves of Hoxa2, Hoxd1 and Pax6 expression may be required to provide positional information for the specification of the diencephalon. PMID- 11209946 TI - Neuroprotection from glutamate toxicity with ultra-low dose glutamate. AB - The protective effects of ultra-low doses (ULD) of glutamate against glutamate toxicity was studied in primary rat spinal, cortical and cerebellar neurons. Neurons were exposed to four subtoxic, ultra-low concentrations of glutamate (10( 18) M, 10(-20)M, 10(-22) M and 10(-30) M) for 72 h and then subsequently challenged with toxic concentrations (25 microM) of glutamate. Neuron viability was consistently 10% higher in spinal and cortical neurons pre-exposed to glutamate concentrations of 10(-18) M and 10(-22) M, and in cerebellar neurons pre-exposed to 10(-20) M and 10(-30) M. Using laser scanning confocal microscopy and the fluorescent calcium probe fluo-3, we found no alterations in intracellular calcium dynamics in the protected cells. This protective effect is consistent with a growing body of evidence for tolerance induced by low-dose toxin exposure but is the first time that such tolerance has been demonstrated with ultra-low glutamate exposure. Our data show that pre-exposure of neuronal cells to ULD glutamate can protect against subsequent exposure to toxic levels of glutamate. PMID- 11209948 TI - Independent short-term variability of spike-like (600 Hz) and postsynaptic (N20) cerebral SEP components. AB - Human scalp-derived somatosensory evoked potentials (SEP) elicited by median nerve stimulation contain an early (20 ms latency) high-frequency (600 Hz) wavelet burst which is supposed to reflect non-invasively the timing of rapidly repeating population spikes in thalamocortical afferences and/or the receiving neocortical cell populations. This burst is superimposed onto the slower (< or = 100 Hz) primary cortical response (N20) representing intracortically generated postsynaptic events. The present study addressed the temporal dynamics and correlation of these response components in awake human subjects and found that at a 3 min time scale the burst response was significantly more variable than the concomitant N20, and that the burst and N20 varied independently of each other. Thus, wavelet burst and N20 represent parallel and partly independent steps in sensory processing at cortical input stages in awake human subjects. We propose that the N20 represents a stable somatosensory input whereas the more fluctuating high-frequency burst could index variable modes of processing, such as a floating focus of attention. PMID- 11209947 TI - Evidence for glutamate receptor mediated transmission at mechanoreceptors in the skin. AB - The functional role of Merkel cells in the mechanosensitivity of the slowly adapting type I responses has been a controversial issue for many years. Here we show, for the first time, that glutamate receptor-mediated transmission is largely responsible for the static component of the slowly adapting type I response. An isolated sinus hair preparation was used to study the two types (I and II) of slowly adapting units. A broad spectrum ionotropic glutamate receptor antagonist kynurenate (1-10 mM) caused reliable and dose-dependent reductions in the static component of type I unit responses to mechanical stimulation. In addition, an amino acid transmitter candidate aspartate applied to the preparation selectively increased responses in type I units but not responses in type II units. This evidence establishes that the Merkel cell is a mechano electric transducer, and challenges prevailing views that the Merkel cell acts merely as a support or target cell in the epidermis. PMID- 11209949 TI - Partial lesions in the anterior forebrain pathway affect song production in adult Bengalese finches. AB - The avian song system consists of two main parts: the descending motor pathway and the anterior forebrain (AF) pathway. The former directly controls the motor act of singing, but the role of the AF pathway in real-time song production is not understood; lesioning a nucleus in the AF pathway in adult zebra finches did not cause any notable effects. Here we show that in a related species of songbirds, the Bengalese finch, a partial lesion located in Area X, a nucleus of the avian basal ganglia that is part of the AF pathway, causes a transient but substantial song motor deficit. This is the first demonstration that the AF pathway is involved in real-time song production in adulthood. PMID- 11209950 TI - Hippocampal, parahippocampal and occipital-temporal contributions to associative and item recognition memory: an fMRI study. AB - The temporal lobe regions involved in memory retrieval were examined using fMRI. During an associative recognition test, participants made memory judgments about the study color of previously presented drawings of objects, and during item recognition tests they made old/new judgments about previously studied objects or new objects. Associative recognition compared with old item recognition led to activations in bilateral hippocampal and parahippocampal regions, as well as in the left middle occipital gyrus. Old item recognition compared with new item recognition led to activation in the left middle occipital gyrus and the left middle temporal gyrus, and relative deactivations in bilateral hippocampal regions. The results indicate that partially distinct temporal lobe regions are involved during recognition memory for item and associative information. PMID- 11209951 TI - Disparity tuning in macaque area V4. AB - Neural processing of stereoscopic depth is conventionally associated with the dorsal (spatial) pathway in primate visual cortex. The role of depth information in the ventral (object) pathway has been less certain. We found prominent tuning for stereoscopic disparity in area V4, an intermediate stage in the ventral pathway. Eighty percent of the cells in our sample exhibited significant disparity tuning over the -1.0 degree to 1.0 degree range, and the majority showed > 2:1 response differences. Tuning function shapes were similar to those reported previously in other visual areas. We observed a significant tuning bias towards crossed (near) disparities. This could reflect an emphasis in the ventral pathway on foreground objects or parts of objects projecting towards the viewer. PMID- 11209952 TI - Musicians and the gamma band: a secret affair? AB - While listening to music, a significant high degree of phase synchrony in the gamma frequency range globally distributed over the brain was found in subjects with musical training (musicians) compared with subjects with no such training (non-musicians). No significant differences were found in other EEG frequency bands. Listening to neutral text did not produce any significant differences in the degree of synchronization between these two groups. For musicians, left hemispheric dominance was found during listening to music. The right hemisphere was found to be dominant for non-musicians in text listening. The high degree of synchronization in musicians could be due to their high ability to retrieve musical patterns from their acoustic memory, which is a cogent condition for both listening to and anticipating musical sounds. PMID- 11209953 TI - First evidence of a delay-dependent working memory-enhancing effect of modafinil in mice. AB - This study investigated the effects of pretest injection of modafinil on delayed spontaneous alternation rates (SA) used to evaluate working memory in C57 Bl/6 mice. In a first experiment, systemic modafinil at 64 mg/kg, but not at 8 mg/kg or 32 mg/kg doses produced a significant increase of alternation scores (intertrial interval (ITI) 60s) when compared with controls. In a second experiment, modafinil (64 mg/kg) enhanced the alternation rates mainly at long (60 s and 180 s) but not at short (5 s) ITIs. Exploratory latencies and activity in a four hole-board apparatus were not modified by modafinil administration. These experiments are the first to demonstrate a delay-dependent working memory enhancing effect of modafinil. PMID- 11209954 TI - Differential prefrontal cortex and amygdala habituation to repeatedly presented emotional stimuli. AB - Repeated presentations of emotional facial expressions were used to assess habituation in the human brain using fMRI. Significant fMRI signal decrement was present in the left dorsolateral prefrontal and premotor cortex, and right amygdala. Within the left prefrontal cortex greater habituation to happy vs fearful stimuli was evident, suggesting devotion of sustained neural resources for processing of threat vs safety signals. In the amygdala, significantly greater habituation was observed on the right compared to the left. In contrast, the left amygdala was significantly more activated than the right to the contrast of fear vs happy. We speculate that the right amygdala is part of a dynamic emotional stimulus detection system, while the left is specialized for sustained stimulus evaluations. PMID- 11209955 TI - Unseen stimuli modulate conscious visual experience: evidence from inter hemispheric summation. AB - Emotional facial expression can be discriminated despite extensive lesions of striate cortex. Here we report differential performance with recognition of facial stimuli in the intact visual field depending on simultaneous presentation of congruent or incongruent stimuli in the blind field. Three experiments were based on inter-hemispheric summation. Redundant stimulation in the blind field led to shorter latencies for stimulus detection in the intact field. Recognition of the expression of a half-face expression in the intact field was faster when the other half of the face presented to the blind field had a congruent expression. Finally, responses to the expression of whole faces to the intact field were delayed for incongruent facial expressions presented in the blind field. These results indicate that the neuro-anatomical pathways (extra-striate cortical and sub-cortical) sustaining inter-hemispheric summation can operate in the absence of striate cortex. PMID- 11209956 TI - Expression of the high-affinity glutamate transporter EAAT4 in mammalian cerebral cortex. AB - RT-PCR, immunocytochemistry and Western blotting were used to study the expression of the glutamate transporter EAAT4 in the cerebral cortex of cat and mouse. By means of RT-PCR we were able to detect EAAT4 mRNA in the cerebral cortex of both species. Sequencing ensured the specificity of the amplified fragment. Immunocytochemistry and Western blotting enabled us to localize EAAT4 protein in cat and mouse cerebral cortex. Intense EAAT4 immunoreactivity was found in the soma and dendrites of neurons mainly of layers II, III and V. For both species, the signal in the cerebellum was very intense and confined to the molecular and Purkinje cell layer. PMID- 11209957 TI - Long-term effects of short-lasting early local inflammatory insult. AB - We examined the long-term effects of a short-lasting (approximately 24 h) inflammatory insult generated by injections of 0.25% carrageenan (1 microl/g) into the hindpaws of newborn (P0) rat pups. At P60 animals which experienced this early inflammatory insult showed significant alterations in the withdrawal responses to noxious stimulation of the affected paws. Furthermore, in the absence of ongoing inflammation, the withdrawal latencies to heat stimulation and withdrawal thresholds to mechanical stimulation were increased by such experience. In the presence of ongoing CFA-induced inflammation, however, the same early experience decreased these parameters of response to noxious stimulation. These data suggest that early inflammatory insult may differentially affect the aspects of nociceptive circuitry involved in transient pain sensitivity and in inflammation-induced hyperalgesia. PMID- 11209958 TI - An fMRI study of stimulus equivalence. AB - In order to study brain activation during the formation of equivalence relations, 12 subjects underwent fMRI during matching-to-sample (MTS) tests of (1) previously trained arbitrary relationships between iconic stimuli and the untrained, emergent relations of (2) symmetry, (3) transitivity, and (4) symmetry with transitivity, plus a test of verbal fluency (VF). Brain activation was similar in all MTS tasks and in the VF task. In particular, both types of task activated dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex bilaterally. However VF, but not the MTS tasks, activated Broca's area. In three of the four MTS tasks, behavioural accuracy was significantly correlated with left lateralisation of DLPFC activity. Brain activation patterns during equivalence thus resembled those involved in semantic processing underlying language, without involving regions concerned with the simple sub-vocal articulation of stimulus names. PMID- 11209959 TI - Definite segregation of cortical neurons projecting to the dorsal column nuclei in the rat. AB - The dorsal column nuclei (DCN) receive a substantial contingent of projections that arise from a number of somatosensory and motor cortical areas. We investigated the spatial organization of these projections in the rat by placing small deposits of two retrograde fluorescent tracers in adjacent foci within the DCN. Single-labeled neurons were abundant in layer V of the primary somatosensory (SI) and motor areas, and in the posterior parietal cortex. More sparse labeling was found in the medial agranular cortex (or MII), and the second somatosensory area. A somatotopic-like arrangement of these neurons was more clearly noticed in the granular zones of SI. Double-labeled neurons were very uncommon, and appeared at border regions where single-labeled cells intermingled. The segregation of these projections supports some differential modulatory effects that the cortex exerts on the somatosensory processing that takes place in the DCN. PMID- 11209960 TI - Antigens of monoclonal antibody NB3C4 are novel markers for oligodendrocytes. AB - We produced NB3C4, a novel monoclonal antibody specific for oligodendrocytes, using human neuroblastoma IMR-32 cells. NB3C4 specifically recognized oligodendrocytes in the CNS, although it bound to neuroblastoma IMR-32 cells and oligodendrocytes in vitro. Double immunofluorescence staining of rat brain using NB3C4 and anti-GST-pi, anti-glial fibrillary acidic protein (GFAP), or anti neurofilament 200 (NF) antibody revealed that anti-GST-pi antibody identified an oligodendrocyte marker recognizing NB3C4-positive cells, while both anti-GFAP and anti-NF antibody did not. Western blotting of rat brain homogenates showed that NB3C4 bound three proteins of 22-28 kDa, while the anti-GST-pi recognized a 27 kDa protein. Therefore, antigens recognized by NB3C4 could be novel markers for oligodendrocytes. PMID- 11209961 TI - Mice over-expressing galanin have elevated heat nociceptive threshold. AB - The neuropeptide galanin may have a role in modulation of nociceptive input at spinal level. Here we report that mice over-expressing galanin exhibit significant elevation of nociceptive threshold to thermal stimulation in comparison to wild-type mice as assessed by the tail flick and paw heat irradiation tests. No change in response to mechanical or cold stimulation was seen. The elevated heat nociceptive threshold in the galanin over-expressing mice was reversed by intrathecal application of the putative galanin receptor antagonist M-35, galanin-(1-12)-pro-bradykinin-(2-9). The results thus support that galanin has an inhibitory function in rodent spinal cord. PMID- 11209962 TI - Sex-specific developmental changes in amygdala responses to affective faces. AB - It is hypothesized that adolescent development involves a redistribution of cerebral functions from lower subcortical structures to higher regions of the prefrontal cortex to provide greater self-control over emotional behavior. We further hypothesized that this redistribution is likely to be moderated by sex specific hormonal changes. To examine developmental sex differences in affective processing, 19 children and adolescents underwent fMRI while viewing photographs of faces expressing fear. Males and females differed in the pattern of their amygdala vs prefrontal activation during adolescent maturation. With age, females showed a progressive increase in prefrontal relative to amygdala activation in the left hemisphere, whereas males failed to show a significant age related difference. There appear to be sex differences in the functional maturation of affect-related prefrontal-amygdala circuits during adolescence. PMID- 11209963 TI - The suprachiasmatic nucleus projects to posterior hypothalamic arousal systems. AB - The suprachiasmatic nucleus (SCN) temporally organizes behavior in part by sustaining arousal during the wake period of the sleep/wake cycle to consolidate adaptive waking behavior. In this study, we demonstrate direct projections from the SCN, in both the rat and the human brains, to perikarya and proximal dendrites of two groups of posterior hypothalamic neurons with axonal projections that suggest they are important in the regulation of arousal, one producing hypocretins (HCT) and the other melanin-concentrating hormone (MCH). In addition, we demonstrate that both HCT and MCH-producing neurons are immunoreactive for glutamate (GLU). These observations support the hypothesis that direct projections from the SCN to the posterior hypothalamus mediate the arousal function of the circadian timing system. PMID- 11209964 TI - The future of fluoroquinolones. AB - The mutant prevention concentration (MPC) is a new measure of antibiotic potency above which a microbe must attain two concurrent resistance mutations for growth. For some C-8-methoxy fluoroquinolone-pathogen combinations, the value of MPC is below human serum drug concentration achieved with standard doses. Although untested clinically, such a low value of MPC, coupled with high serum concentration, should allow these fluoroquinolones to restrict severely the selection of resistant mutants when used as monotherapy. Compounds that cannot meet the MPC-pharmacokinetic criterion will enrich resistant mutants unless they are a part of combination therapy. Separation of fluoroquinolones into groups suitable for monotherapy or for combination therapy, followed by appropriate adminstration, may help extend the lifespan of the fluoroquinolones. PMID- 11209965 TI - Predictors of liver-related complications in patients with chronic hepatitis C. AB - Chronic hepatitis C is the leading cause of decompensated liver disease requiring liver transplantation and a major cause of hepatocellular carcinoma (HCC). In liver clinic series, about 20% of those chronically infected with hepatitis C virus (HCV) develop cirrhosis over 20 years. From epidemiological data, however, it is clear that certain subgroups of patients are more likely to develop liver related complications than others. Both host and viral factors have been implicated in individual susceptibility to adverse outcomes. The impact of host factors, such as alcoholism, is now well defined, and viral factors, such as genotype and viral load, appear to be less influential than previously considered. Coinfections with HIV, hepatitis A virus (HAV) and hepatitis B virus (HBV) may influence the rate of fibrotic progression and the subsequent development of complications in patients with chronic hepatitis C. The stage of fibrosis on biopsy and biochemical markers, such as a low serum albumin, can help identify patients who are more likely to develop complications. The role of the immune system in modifying the course of HCV is only now being defined. This editorial explores the role of host and viral factors in the development of liver related complications in HCV-infected individuals. PMID- 11209966 TI - Brain imaging and the effects of caffeine and nicotine. AB - Caffeine and nicotine are the most common psychostimulant drugs used worldwide. Structural neuroimaging findings associated with caffeine and nicotine consumption are limited and primarily reflect the putative relationship between smoking and white matter hyperintensities (WMH), a finding that warrants further appraisal of its clinical implications. The application of newer brain imaging modalities that measure subtle haemodynamic changes or tissue-based chemistry in order to better elucidate brain functional processes, including mechanisms underlying addiction to nicotine and caffeine and the brain functional consequences, provide intriguing findings. Potential influences of caffeine and nicotine on the functional contrast, or metabolic response, to neural activation also necessitates the careful appraisal of the effects that these commonly used drugs may have on the results of functional imaging. PMID- 11209967 TI - Immunopathogenesis of HTLV-I-associated myelopathy/tropical spastic paraparesis. AB - The main pathological feature of human T-lymphotropic virus type I (HTLV-I) associated myelopathy/tropical spastic paraparesis (HAM/TSP) is chronic inflammation of the spinal cord characterized by perivascular cuffing of mononuclear cells accompanied by parenchymal lymphocytic infiltration. Although the exact mechanism of the pathogenesis of HAM/TSP is still obscure, immunological abnormalities arising from a high HTLV-I proviral load in peripheral blood lymphocytes (PBL) play an important role in the pathological process of spinal cord lesions in HAM/TSP patients. The relationship between HLA haplotype and the risk of the occurrence of HAM/TSP will be elucidated by results from studies of HLA allele typing. In addition, recent data indicate that HTLV-I and its expression are localized in infiltrated lymphocytes within the spinal cord lesions of HAM/TSP patients rather than in resident central nervous system (CNS) parenchymal cells. Although a bystander damage of the surrounding CNS tissues, in which CD8+ HTLV-I-specific cytotoxic T lymphocyte (CTL) attack HTLV-I infected lymphocytes, might be involved in the pathological events of the spinal cords of HAM/ TSP patients as one of the actual pathogenetic mechanisms, heightened transmigrating activity of HTLV-I-infected CD4+ T lymphocytes to the CNS tissues may have a key role in the development of HAM/TSP. Therefore, although the exact mechanism underlying the high HTLV-I proviral load in PBL in HAM/TSP patients is still unknown, we must consider therapeutic approaches in HAM/TSP that eliminate HTLV-I-infected CD4+ T lymphocytes. PMID- 11209968 TI - The replacement of oestradiol and progesterone in very premature infants. AB - The idea of replacing 17beta-oestradiol (E2) and progesterone (P) in preterm infants is based on the observation that during pregnancy E2 and P plasma concentrations rise in the mother and the fetus by a factor of 100. Disruption of the placental supply of these hormones is a physiological event for an infant delivered at term. A preterm infant is deprived from this supply at an earlier developmental stage. In vitro and in vivo data are discussed, and they highlights the potential benefit of E2 and P on the development of different organ systems. The postnatal replacement of E2 and P has the aim of maintaining in utero plasma concentrations. In the first randomized clinical study in 30 extremely preterm infants, E2 and P were replaced postnatally for a total of 6 weeks. With a median intravenous replacement of 8.4 micromol/kg/day of E2 (4.2-22.9) and 67.4 micromol/kg/day of P (35.7-87.0), plasma levels of E2 and P were maintained within the intrauterine reference values of 7.3-22.0 nmol/L and 0.95-1.9 micromol/L, respectively. Three- to sixfold higher dosages were needed via the transepidermal route. Trends towards an improved postnatal bone mineral accretion and a reduced incidence of chronic lung disease were found. Further studies are warranted to clarify the potentially important role of E2 and P for the postnatal development of an extremely preterm infant. PMID- 11209969 TI - Autologous blood stem cell transplantation as therapy for autoimmune diseases. AB - Autologous stem cell transplantation (ASCT) is starting to be investigated as a potential therapy for severe refractory autoimmune disease including rheumatological, neurological and haematological diagnoses. Increasing numbers of cases are now reported in the literature. Data from all transplanted patients are being collated in a centralized register by the European Group for Blood and Marrow Transplantation (EBMT) and the European League against Rheumatism (EULAR) to enable effective evaluation of the safety and efficacy of this promising technique. Thus far, results have been encouraging; however, more treatment related deaths were reported in multiorgan diseases such as scleroderma and less in diseases such as rheumatoid arthritis, which confirms the importance of careful patient selection. Optimization of mobilization, conditioning regimen and graft manipulation is required to maximize efficacy without increasing mortality and morbidity. The use of maintenance therapy after ASCT in order to prevent relapse needs to be explored. Following individual case reports and small cohort studies, the next step is likely to involve multicentre randomized controlled trials. PMID- 11209970 TI - Intracoronary radiotherapy for prevention of restenosis after percutaneous coronary interventions. AB - More than 50 different pharmacological and mechanical interventions have been tested to date for prevention of vascular restenosis without success. Intracoronary radiotherapy is the first one showing promise of significantly attenuating neointimal proliferation, causing positive vascular remodelling and thus inhibiting restenosis. This promising modality has moved from animal experiments via safety and feasibility testing into the phase of clinical trials of efficacy in large numbers of patients. While ongoing research continues to search for new sources and delivery techniques, currently available technology is being optimized. The randomized clinical trials conducted to date have shown consistently a reduction of target site restenosis rates by 55-79%. Lower incidence of major adverse cardiac events after radiotherapy has also been demonstrated, primarily as a result of reduction in target site and target vessel revascularization rates. However, experimental and clinical research has identified two major complications of this approach: stenosis at the ends of the radiation zone ('edge effect' or 'candywrapper') as well as late thrombosis (beyond 30 days after intervention) of the angioplasty or stent site. If these two adverse effects can be minimized, intracoronary radiotherapy may prove to be a major breakthrough in percutaneous coronary interventions. PMID- 11209971 TI - The GlucoWatch biographer: a frequent automatic and noninvasive glucose monitor. AB - The GlucoWatch (Cygnus, Inc, Redwood City, CA, USA) biographer provides automatic, frequent and noninvasive blood glucose measurements for up to 12 h. The device extracts glucose through intact skin where it is measured by an amperometric biosensor. Clinical trials in a variety of environments have shown that the biographer provides accurate and precise glucose measurements when compared with serial fingerstick blood glucose measurements. Mean difference between these measurements was 0.26 mmol/L in the home environment (r = 0.80). Over 94% of biographer readings were in the clinically acceptable A+B region of the Clarke Error Grid. A slight positive bias is observed for the biographer readings at low glucose levels. Biographer precision, as measured by coefficient of variation (CV)%, is approximately 10%. The low glucose alert function of the biographer was able to detect up to 75% of hypoglycaemic episodes with a low false alert level. Skin irritation, characterized by erythema and oedema was either nonexistent or mild in over 87% of subjects and resolved in virtually all subjects without treatment in several days. The GlucoWatch biographer has been shown to be a safe and effective method to track glucose level trends and patterns, which should enable improved glycaemic control for many patients. PMID- 11209972 TI - High-density lipoprotein: gene-based approaches to the prevention of atherosclerosis. AB - Although the atheroprotective role of high-density lipoprotein (HDL) has been well documented in epidemiological and animal studies, highly effective therapeutic approaches for the selective increase of plasma HDL levels or function are not yet available. Several mechanisms by which HDL exerts an atheroprotective effect have been proposed on the basis of experiments in vitro and in vivo. These mechanisms include directing excess cellular cholesterol from the peripheral tissues to the liver in 'reverse cholesterol transport', inhibiting oxidative modification or aggregation of LDL, and modulating inflammatory responses to favour vasoprotection. This review gives an overview of the genes regulating these mechanisms, such as those encoding apolipoprotein AI, lecithin:cholesterol acyltransferase (LCAT), scavenger receptor B1 (SR-BI), and the ATP-binding cassette transporter 1 (ABC1), and the potential to exploit them to develop gene-based therapeutic approaches to increase the level or function of HDL. PMID- 11209973 TI - Association of CagA-positive infection with Helicobacter pylori antibodies of IgA class. AB - cagA gene, the best known virulence factor of Helicobacter pylori, codes for an immunodominant CagA protein. In this study, CagA antibodies of the IgG class were measured by immunoblot or enzyme immunoassay in subjects with positive H. pylori serology, and the presence of CagA antibodies was compared with that of H. pylori antibodies of IgA and IgG classes. Serum samples were available for a total of 1,481 subjects, including gastroscopied patients with biopsy-verified H. pylori infection, smoking men with a normal or low serum pepsinogen I level indicating atrophic corpus gastritis, and subjects who later developed gastric cancer and their matched controls. CagA antibodies were significantly more prevalent among individuals with elevated H. pylori antibody titres of the IgA class than in those with IgG antibodies only, with the exception of a small subgroup of individuals who later developed gastric cancer. CagA-positive H. pylori strains seem to induce an immune response with a markedly higher frequency of IgA than what is found in inflammation caused by CagA-negative strains. The presence of serum IgA antibodies to H. pylori seems to indicate a higher risk for CagA positive H. pylori infection and possibly more severe late sequelae of the disease. PMID- 11209974 TI - Genetics of platelet receptor single-nucleotide polymorphisms: clinical implications in thrombosis. AB - Several single-nucleotide polymorphisms (SNPs) of platelet receptors have been implicated to be associated with an increased risk of arterial thrombosis; this review focuses on the mechanisms and the clinical significance of two specific single-nucleotide polymorphisms, ie the GP IIIa L33P (=PlA1/2) and the GP Ia 807 C/T. Whereas the mechanism of P1A2 is thought to result from 'gain of receptor function' (and there is still considerable controversy on this subject), the collagen receptor SNP is associated with an increased number of receptors on the platelet surface, thus offering a plausible explanation for the observed increased interaction with collagen and the increased risk of thrombotic events reported in some studies but not in others. Overall, the presently available (controversial) data do still not allow the conclusion that the GPIIIa polymorphism alone represents a cardiovascular risk factor in the general population. A number of mechanisms and a series of studies suggest, however, that it may be a risk factor in certain subgroups of patients or in a number of clinical situations. The GPIa SNP discussed seems to be a mild risk factor that is particularly important in synergism with known risk factors, such as smoking, hypertension, diabetes or proteinuria, etc, which may enhance its contribution to the overall cardiovascular risk. PMID- 11209975 TI - Platelet activation by ADP: the role of ADP antagonists. AB - ADP plays a key role in haemostasis and thrombosis. Despite its early identification in 1961 as the first known aggregating agent, the molecular basis of ADP-induced platelet activation is only beginning to be understood. Two purinergic receptors contribute separately to the complex process of ADP-induced platelet aggregation: the P2Y1 metabotropic receptor responsible for mobilization of ionized calcium from internal stores, which initiates aggregation, and P2Y receptor coupled to adenylyl cyclase inhibition, which is essential for the full aggregation response to ADP and stabilization of platelet aggregates. The latter is the molecular target of the ADP-selective antiaggregating drugs ticlopidine and clopidogrel and the ATP analogues of the AR-C series. In addition, it is probably defective in patients with a bleeding diathesis characterized by selective impairment of platelet responses to ADP. Finally, the P2X1 ionotropic receptor is also present in platelets, but its role is not yet known. Studies with P2Y1 knock-out mice as well as the use of selective P2Y1 antagonists have shown that, in addition to the P2Y receptor, which is the target of clopidogrel, the P2Y1 receptor is an important potential target for new antithrombotic drugs. PMID- 11209976 TI - Role of von Willebrand factor in platelet thrombus formation. AB - Haemostasis is the process that arrests bleeding from wounds, preventing blood from flowing outside of the vascular bed. Thrombosis is an abnormal condition in which the vascular lumen becomes occluded by a mass constituted primarily of aggregated platelets and polymerized fibrin. These thrombi impede the normal flow of circulating blood, becoming the acute cause of diseases that represent a great health concern in the developed world. Haemostasis and thrombosis are two aspects of the same function, ie the biological response to vascular injury leading to formation of a thrombus, which is platelet-rich specifically in the arteries. In either situation, von Willebrand factor is a crucial participant in the process as its main biological activity is to support platelet adhesion and aggregation in vessels where rapid blood flow challenges the firm attachment of thrombi to the vascular wall or exposed extravascular tissues. Advances in understanding the structure and function of von Willebrand factor indicate that this protein, for its unique biomechanical properties, may be a potentially useful target of antithrombotic drugs. PMID- 11209977 TI - Cyclo-oxygenase products and atherothrombosis. AB - The advent of selective inhibitors of the cyclo-oxygenase (COX)-2 enzyme has afforded the opportunity to reduce the incidence of gastrointestinal complications of traditional nonsteroidal anti-inflammatory drugs (NSAIDs). The widespread use of these drugs has increased interest in their role in the cardiovascular system. Although deletion of the prostacyclin receptor (the IP) accelerates atherogenesis in the mouse, retention of one copy of the IP is atheroprotective. This is consistent with the failure of biochemically defined, selective doses of a COX-2 inhibitor to accelerate atherogenesis in the mouse, despite suppressing prostacyclin biosynthesis by roughly 60%. Inhibition of both COX isozymes, by contrast, markedly retards atherogenesis. Consistent with these observations, antagonism of the thromboxane receptor (the TP) retards atherogenesis and diminishes the proliferative response to vascular injury in the mouse. Even partial suppression of prostacyclin (without coincident inhibition of platelet COX-1-dependent thromboxane formation) by COX-2 inhibitors may be undesirable in acute vascular occlusive syndromes. However, these drugs are unlikely to accelerate progression of the underlying vascular disease. By contrast, the effects of TP antagonists, aspirin, and even traditional NSAIDs on atherosclerotic plaque progression merit further evaluation in humans. PMID- 11209978 TI - Antiphospholipid antibodies in arterial thrombosis. AB - The high correlation between the IgG isotype of anticardiolipin antibodies (aCLs) and clinical thrombosis was first documented in 1983, and this observation was confirmed in subsequent studies. In addition, the frequency of fetal loss and thrombocytopenia was increased in this group of patients. These findings were termed the antiphospholipid syndrome (APS). This syndrome was mostly seen in patients with systemic lupus erythematosus (SLE), but it soon became clear that also other patients not suffering from defined SLE might exhibit features of APS. aCL in APS patients are detected in immunoassays by using solid phase cardiolipin as a putative antigen. However, antibodies directed against phospholipid-binding plasma or serum proteins, beta2-glycoprotein I (beta2-GPI), in particular, are also detected. Many recent studies have indicated that one of predominant antibodies that has been identified as aCL in APS patients is against beta2-GPI rather than any of the negatively charged phospholipids. The epitopes recognized by anti-beta2-GPI antibodies raised in APS patients are composed of discontinuous amino acid sequences from the IV domain of human beta2-GPI. These epitopes are cryptic when beta2-GPI does not interact with anionic phospholipids. An early event in atherosclerosis is the accumulation of cholesterol-laden foam cells, which originate mainly from monocyte-macrophage cells by their uptake of chemically modified low-density lipoprotein (LDL). We found that beta2-GPI binds directly to oxLDL, and that the complex of oxLDL and beta2-GPI is subsequently recognized by aCL (anti-beta2-GPI) to be taken up by macrophages. While the pathogenesis of this accelerated atherosclerosis is likely to be multifactorial, it is possible that antiphospholipid antibodies, including aCL (anti-beta2-GPI antibodies), may have contributed to the formation of atherosclerotic lesion. PMID- 11209980 TI - Autoantibodies associated with atherosclerosis. AB - Atherosclerosis is a multifactorial pathological process. In recent years, the immune factors associated with its initiation and progression have been investigated intensively. Several autoantigens and their respective autoantibodies have been suggested as factors in atherogenesis. This manuscript provides a review of autoantibodies directed towards oxidized low-density lipoprotein (oxLDL), cardiolipin, beta2-glycoprotein-I and heat-shock protein 60/65, and their association with human and murine atherosclerosis. PMID- 11209979 TI - Lupus anticoagulant in cardiovascular diseases: the role of beta2-glycoprotein I. AB - The presence of antiphospholipid antibodies (aPL) in plasma is an important risk factor for the development of thrombosis. A major breakthrough came in 1990 with the finding that aPL do not react with phospholipids per se, but are directed towards beta2-glycoprotein I, a plasma protein with affinity for anionic phospholipids. Afterwards other plasma proteins with affinity for phospholipids have been identified as possible antigens for aPL. Human beta2-glycoprotein I is a heavily glycosylated plasma protein that has been implicated in the binding of aPL to negatively charged phospholipids. We recently solved the crystal structure of beta2-glycoprotein I. In this review we will discuss what the 3-dimensional structure teaches us about the role of beta2-glycoprotein I in the pathogenesis of the thrombotic complications characteristic of the antiphospholipid syndrome. PMID- 11209981 TI - Treatment of thrombosis associated with immunological risk factors. AB - The clinical management of the antiphospholipid syndrome is aimed at assessing the thrombotic risk of an individual in order to undertake primary prevention for the asymptomatic subject positive for antiphospholipid antibodies or prophylaxis of major ischaemic events for the patient who has already experienced thrombosis. Lack of immunological parameters with a clear predictive value and the current concept that thrombosis is a multifactorial disease suggest that all the known acquired and genetic thrombotic risk factors should be taken into account in antiphospholipid syndrome. Low-dose aspirin and hydroxychloroquine have been proven useful in primary prevention. While convincing evidence has been provided that aspirin and hydroxychloroquine do not prevent secondary thrombosis, much debate has recently developed on the level of oral anticoagulation needed to guarantee this prevention. Main concerns are also related to duration of anticoagulation therapy, risk of bleeding, and the increased risk of thrombosis as a result of withdrawal of the anticoagulant. Low-molecular-weight heparin has recently emerged as a valid and safe alternative for those conditions that require transient interruption or withdrawal of anticoagulation. Although treatment of the catastrophic antiphospholipid syndrome is largely empirical, the therapeutic approach based on plasmapheresis associated with immunosupression or intravenous immunoglobulin seems to be the most promising. Most attention has recently been paid to the role of oxidative stress in the pathogenesis of antiphospholipid syndrome, as a correlation between lipid peroxidation and antiphospholipid antibodies has been demonstrated. Our studies showed that lipid peroxidation may contribute to the activation of the clotting system observed in antiphospholipid syndrome and that markers of both procoagulant state and increased lipid peroxidation can be modified by experimental antioxidant treatment. PMID- 11209982 TI - Hyperhomocysteinaemia and atherothrombosis. AB - Homocysteine (Hcy) is a sulfhydryl amino acid derived from the metabolic conversion of methionine that is dependent on vitamins (folic acid, B12 and B6) as cofactors or cosubstrates. In 1969, McCully first reported the presence of severe atherosclerotic lesions in patients with severe hyperhomocysteinaemia and hypothesized the existence of a pathogenic link between hyperhomocysteinaemia and atherogenesis. Several case-control and cross-sectional studies confirmed the initial hypothesis of McCully, showing that also moderate hyperhomocysteinaemia is associated with a heightened risk of occlusive arterial disease. Less consistent results have been reported by prospective cohort studies of subjects who were healthy at the time of their enrollment, whereas prospective cohort studies of patients with overt coronary artery disease or other risk conditions consistently confirmed the association between moderate hyperhomocysteinaemia and the risk of cardiovascular morbidity and mortality. More recently, an association between moderate hyperhomocysteinaemia and heightened risk of venous thromboembolism has been documented, suggesting that hyperhomocysteinaemia might be involved not only in atherogenesis, but also in thrombogenesis. The mechanisms by which hyperhomocysteinaemia might contribute to atherogenesis and thrombogenesis are incompletely understood. The mainstay of treatment of hyperhomocysteinaemia is folic acid, alone or in combination with vitamins B12 and B6. Although it is quite clear that vitamins effectively reduce the plasma levels of total Hcy, we do not yet know whether they will decrease the risk of vascular disease. The results of ongoing randomized, placebo-controlled, double blinded trials on the effects of vitamins on thrombotic risk will help in defining whether the relationship between hyperhomocysteinaemia and thrombosis is causal, and will potentially have a dramatic impact on the prevention of thromboembolic events. PMID- 11209983 TI - Acute and prolonged treatment with low-molecular-weight heparin therapy in patients with unstable coronary artery disease. AB - Unstable angina and non-ST-segment elevation myocardial infarction (MI) are known as unstable coronary artery disease (UCAD). They are syndromes that share a common pathobiology and represent a frequently encountered and potentially life threatening medical condition. Acute-phase treatment with aspirin is associated with a significant reduction in death and non-fatal MI in patients with UCAD. This benefit is enhanced by the addition of unfractionated heparin (UFH) to the treatment strategy; however, UFH requires careful monitoring and titration. In contrast, low-molecular-weight heparins (LMWHs), produced by chemical or enzymatic depolymerization of UFH, yield a predictable and consistent pharmacokinetic profile and anticoagulant response making them an attractive alternative treatment to UFH in patients with UCAD. In several studies, acute phase treatment with LMWH has been shown to be at least as effective and safe as UFH. The optimal duration of treatment with LMWH is an important question that has been influenced by the observation that reactivation of coagulation occurs following the early and abrupt discontinuation of heparin treatment. In early trials, such as FRISC (Fragmin during instability in coronary artery disease) and FRIC (Fragmin in unstable coronary artery disease), the results of extended treatment were inconclusive; however, the trial populations included patients of relatively low risk and used a once-daily dosing regimen. In the TIMI 11B (Thrombolysis in myocardial infarction) extended treatment beyond the few days of acute treatment with enoxaparin did not add to the beneficial LMWH effect, but in this study 40% of the high-risk patients did not continue on extended treatment. The findings derived from the FRISC II trial, which used a twice-daily dose of dalteparin sodium, suggest a benefit for up to 45 days with extended treatment in high-risk UCAD patients. Although an early invasive treatment strategy is particularly beneficial, patients in whom early revascularization is not possible should be considered for extended treatment with dalteparin sodium awaiting percutaneous coronary intervention. PMID- 11209984 TI - Heparin-induced thrombocytopenia: laboratory diagnosis and management. AB - Heparin-induced thrombocytopenia (HIT), a drug-induced immunohaematological adverse reaction, is a rare but potentially very severe condition. The main problem for this complex syndrome is its recognition and management, which should be as early as possible to avoid the development of life-threatening complications. Most studies have reported heterogeneous populations of patients with other diseases that potentially induce thrombocytopenia. There is no gold standard diagnostic criteria, and we have established a score with anamnestic criteria that allows us to evaluate the likelihood of HIT. In clinical practice, the diagnosis is based on the analysis of clinical features and laboratory tests. Platelet aggregation test (PAT) and an ELISA test (heparin platelet-induced antibodies) are generally performed by expert laboratories to confirm the occurrence of HIT. In our experience, both tests are concordant in the majority of patients. PAT seems to correlate better with the clinical features while ELISA appears more specific. Regarding their limits, both are complementary in the determination of HIT diagnosis coupled to the clinical score system. The treatment often requires a multidisciplinary approach. Danaparoid (Orgaran) or lepirudin (Refludan) are the two alternative treatments for HIT patients with marketing approval. To avoid further exposure to heparin, every HIT patient should carry a written document that confirms the immunoallergy. PMID- 11209985 TI - Future possibilities in the regulation of the extrinsic pathway: rFVIIa and TFPI. AB - Following vessel wall injury, tissue factor (TF) is being exposed and forms complexes with the already activated FVII (FVIIa) present in the circulating blood, providing a limited amount of thrombin molecules that activate a number of coagulation proteins as well as the platelets. As a result of activation with thrombin the platelet surface exposes negatively charged phospholipids to which activated coagulation proteins bind tightly, and full thrombin generation occurs, resulting in the conversion of fibrinogen into fibrin. After the first FXa is formed, the tissue factor pathway inhibitor (TFPI) forms a complex with FXa. In the next step a quaternary complex is being formed, TF/FVIIa/FXa/TFPI, which inhibits the first step of the haemostatic pathway. Recombinant FVIIa (rFVIIa) has been developed for use as a haemostatic agent (NovoNordisk A/S, Denmark). Inactivated rFVIIa (rFVIIai) has also been prepared, and it has similar binding capacity to TF as rFVIIa but it blocks the catalytic activity of the TF complex. In various animal models rFVIIai has been demonstrated to prevent or diminish immediate thrombus formation at the site of vessel wall injury (athroplasty or other forms of mechanical injury) as well as the development of long-term intima thickening. Also, topical application of rFVIIai was found to block the formation of a thrombus. rFVIIai was shown to have an anti-inflammatory effect in lipopolysaccharide (LPS)-induced sepsis, and postischaemic reperfusion injury was found to be reduced by the administration of rFVIIai. In a limited number of patients undergoing percutaneous transluminal coronary angioplasty (PTCA), rFVIIai was observed to allow PTCA to be performed at lower doses of heparin than what has been reported previously. Recombinant TFPI has been shown to attenuate the lethal inflammatory and coagulopathic response. Furthermore, topical application of rFVIIai has been found to increase the patency rate in a model of graft surgery. PMID- 11209986 TI - Thrombomodulin: a linker of coagulation and fibrinolysis and predictor of risk of arterial thrombosis. AB - Thrombomodulin (TM) binds thrombin, changes thrombin conformation and allows thrombin to activate protein C and thrombin-activatable fibrinolysis inhibitor (TAFI). Activated protein C and TAFI inhibit coagulation and fibrinolysis, respectively. TM is, thus, a linker of endogenous control of coagulation and fibrinolysis. Plasma soluble TM, cleaved products of cellular TM, also have anticoagulant and antifibrinolytic properties. TM plays an important role in thromboresistance. Prospective studies show that a high plasma TM level is associated with a low risk of developing coronary heart disease. The plasma TM level may reflect the level of endothelial TM expression. TM expression levels are influenced by multiple gene polymorphisms. Several of the polymorphisms are probably associated with coronary heart disease. PMID- 11209987 TI - Hypofibrinolysis and increased PAI-1 are linked to atherothrombosis via insulin resistance and obesity. AB - Plasminogen activator inhibitor 1 (PAI-1) is the primary physiological inhibitor of plasminogen activation in vivo. Circulating PAI-1 levels are elevated in patients with coronary heart disease and may play an important role in the development of atherothrombosis by decreasing fibrin degradation. Increased PAI-1 expression can also directly influence vessel wall remodelling. Prospective cohort studies have underlined the association between increased plasma PAI-1 levels and the risk of coronary events, but the predictive capacity of PAI-1 disappeared after adjustments for insulin resistance markers. The insulin resistance syndrome, which is characterized partly by obesity with visceral fat accumulation, is considered as a major regulator of PAI-1 expression. Recently, production of PAI-1 by adipose tissue, in particular by fat from omentum, has been evidenced, and it has been proposed that it could be responsible for the elevated plasma PAI-1 level observed in insulin resistance. The role of stroma cells, tumour necrosis factor (TNF)-alpha and transforming growth factor (TGF) beta as possible enhancers of PAI-1 synthesis are presently emphasized. Glucocorticoids and insulin may also be implicated. Moreover, a weak genetic control of plasma PAI-1 concentration has been described in patients with high plasma levels of PAI-1. The role of PAI-1 in the development of adipose tissue metabolism is important to consider as PAI-1 -/- mice submitted to a high-fat diet showed changes in cell composition of adipose tissue and in plasma insulin and triglyceride levels. PMID- 11209988 TI - Fibrinolytic factors and atherothrombotic events: epidemiological evidence. AB - The fibrinolytic system is important in thrombus resolution at the site of atherosclerotic plaque rupture. The usual levels of plasma fibrinolytic factors have been hypothesized to be important in predicting atherothrombotic events. In this report, prospective clinical, prospective epidemiological, and genetic epidemiological studies of fibrinolytic factors and incident cardiovascular disease are reviewed. Many prospective studies have reported an unadjusted positive association between plasma fibrinolytic markers (eg, tissue plasminogen activator antigen or plasminogen activator inhibitor antigen) and risk of cardiovascular disease. The association tends to be strong and demonstrate a dose response, but often becomes statistically nonsignificant after adjustment for other risk factors. About half of the genetic epidemiological studies suggest that a polymorphism of a gene coding for fibrinolysis may be associated with cardiovascular disease, but that the relative risk is modest, at best. Thus, epidemiological evidence to date is inconclusive about whether impaired fibrinolysis may be a 'cause' of atherothrombotic events. In fact, alterations of plasma fibrinolytic factors might be a 'consequence' of atherosclerosis. At present, it seems premature to recommend routine measurement of fibrinolytic factors to identify patients at risk of cardiovascular disease events. Some directions for future research on this topic are offered. PMID- 11209989 TI - St. John's Wort. AB - OBJECTIVE: The objective of this article is to review the current knowledge of the pharmacology, sites of action, and therapeutic effectiveness of St. John's Wort. METHOD: The method used was a review of the available literature, using keywords to search the medline database. Bibliographies of the papers, thus obtained, were searched for further documents not referenced by medline. We reviewed papers from this collection. RESULTS: This review reveals that most of the available data on efficacy and safety of St. John's Wort involve its use in mild to moderate depression. Much, but not all of the prevailing opinion is positive. Nevertheless, the quality of therapeutic trials vary so greatly that definitive conclusions are not possible. Both the source and mode of St. John's Wort's therapeutic effect are unclear. We need further controlled studies of effectiveness, safety, and mode of action. In addition to its use in depression, there are reports suggesting possible therapeutic effects in other conditions such as certain malignancies and infections, but these are far too preliminary to permit any conclusions. PMID- 11209990 TI - Anxiety and functional status in older primary care patients. AB - OBJECTIVE: The aim of this study was to test the hypothesis that anxiety in older primary care patients is associated with functional impairment after controlling for depression and medical comorbidity. METHOD: Primary care patients (n = 303), aged sixty or older were interviewed with a series of instruments designed to measure psychiatric symptoms including anxiety, depression, medical illness burden, and both examiner-rated and self-reported functional status. Anxiety was measured by the anxiety item of the Hamilton Rating Scale for Depression and the anxiety items of the Medical Outcomes Study Short Form SF-36. Multiple regression techniques were used to examine the association of anxiety with functional status after controlling for age, gender, education, medical burden, and depression. RESULTS: When controlled for depression and medical morbidity, increased anxiety predicted poorer social function. Anxiety was not independently associated with more basic activities of daily living. CONCLUSIONS: Further studies with more comprehensive measures of anxiety are warranted to clarify the relationships between anxiety and functional status. PMID- 11209991 TI - The design, implementation, and acceptance of a primary care-based intervention to prevent depression relapse. AB - OBJECTIVE: This article describes the conceptual underpinnings, implementation, and participation rates of a twelve-month low-intensity primary care-based intervention to prevent depression relapse. The intervention was designed to address the inherent problems in delivery of effective maintenance treatment in a population based sample of primary care patients. METHODS: Patients at high risk of relapse based on psychiatric history who recovered from depression six to eight weeks after initiation of pharmacotherapy by their primary care physician were eligible; 194 were randomized to receive the intervention. The intervention combined education about depression, motivation-enhancing shared decision-making regarding the use of maintenance pharmacotherapy, and cognitive-behavioral strategies. The program included two visits with a Depression Prevention Specialist working in tandem with the primary care physician at the primary care clinic, with supervision and back up from a consulting psychiatrist, proactive follow-up telephone calls and mailed personalized feedback. RESULTS: Ninety-three percent of patients attended both in-person visits; 97 percent attended one visit. Eighty percent of patients completed all three follow-up telephone calls, and 85 percent returned at least one mailed feedback form; 48 percent returned all four forms. Offered a menu of options for self-management, most patients chose medication as well as a variety of behavioral strategies. At six months, 72 percent ofpatients and at twelve months 62 percent of patients remained on antidepressant medication. CONCLUSIONS: We conclude that it is feasible to integrate a low intensity, twelve-month relapse prevention intervention for depression into a primary care clinic. PMID- 11209992 TI - The relationship between trauma, PTSD, and medical utilization in three high risk medical populations. AB - OBJECTIVE: Increased use of medical and psychiatric services has been reported as a correlate of exposure to trauma. Recent studies suggest that: 1) physical and sexual abuse traumas are particularly associated with increased utilization and 2) posttraumatic stress disorder (PTSD), a common sequela of abuse, mediates the relationship between trauma exposure andelevated utilization. The goal of this study was to explore the relationships between trauma, abuse, PTSD, and medical utilization in three medical help seeking groups reported to be at high risk for trauma exposure. METHOD: One hundred and seven patients receiving care at a university-affiliated medical center were surveyed for trauma history and PTSD using the Trauma History Questionnaire (THQ) and the PTSD Checklist (PCL). The sample included: forty-eight gynecologic outpatients, thirty-five inpatients with seizure disorders, and twenty-four psychiatric inpatients with non-PTSD admitting diagnoses. Medical utilization data were obtained from a computerized medical center data base. RESULTS: Ninety-six patients reported a trauma history. Of these patients, sixty-six reported abuse and forty-five qualified for PTSD diagnoses. Total number of traumas and reported sexual and physical abuse correlated significantly with elevated medical utilization and PTSD prevalence. PTSD diagnosis was not significantly correlated with utilization, but the five highest utilizers received PTSD diagnoses. CONCLUSIONS: Study results supported hypotheses regarding the relation of trauma exposure to medical utilization, but were less clear about the mediating role of PTSD. These findings suggest that routine screening of high-risk patient groups might promote timely identification of trauma history and PTSD, and subsequently impact health care utilization. PMID- 11209993 TI - Childhood experiences and adult behavior in a group of women with pain accounted for by psychological factors and a group recovered from major depression. AB - OBJECTIVE: In this study twenty-four women with pain accounted for by psychological factors (DSM-IV, 307.80) and twenty-four with major depression diagnosed according to DSM-III-R were compared to study the relationship between pain and depression. METHOD: They were examined by a semi-structured, tape recorded interview to study their childhood experiences and adult behavior. The interviews were rated by two independent and blind raters. Interrater correlation (Cohen-Kappa) varied between good and close agreement. RESULTS: Of childhood experiences, "brutality between parents," "brutality toward child," and "sexual abuse" were often found in both groups and were more strongly represented in these than in comparison groups of former studies. As adults, the pain group had experienced more serious illness (p = 0.037) and surgery (p = 0.014). The depression group more often had a history of depression (15/24 vs. 4/24; p = 0.001). The pain group spoke negatively of its physicians (p = 0.001), was more hostile during the interview (p = 0.041), was less convinced of the benefit of the hospital stay (p = 0.029), felt less self-responsible, and was more pessimistic (p = 0.013). The pain patients also provoked negative emotions in the raters, whereas the latter's reaction to the depression group was compassion and interest (p = 0.0005) (Pearson's chi2 and Fisher's exact tests). CONCLUSIONS: The results show that negative childhood experiences are prominent and similar in patients with pain accounted for by psychological factors and in patients after major depression. Adult behavior, however, is very different. PMID- 11209994 TI - The clinical applications of Mini-Mental State Examination in geropsychiatric inpatients. AB - OBJECTIVE: This study investigated the association between Mini-Mental State Examination (MMSE) scores and diagnosis, computerized tomographic scans or electroencephalogram findings in geropsychiatric inpatients (age > or = 65). METHOD: We analyzed the MMSE records of patients sixty-five and older who had been hospitalized in our psychiatric ward during a nine-year period. Case data were collected by review of chart records. RESULTS: In these patients, MMSE scores were significantly different among the seven diagnostic groups included. Demented patients had the lowest MMSE scores. Patients who had abnormal findings on computerized tomographic scans or electroencephalogram had lower MMSE than patients with normal findings. CONCLUSION: Our findings suggest that the MMSE is a useful screening instrument for organicity in the geropsychiatric inpatients. However, because of the lower average MMSE score in geropsychiatric inpatients, the optimal cut-offpoint of MMSE for dementia should be lower than those used in other populations. PMID- 11209995 TI - Postpartum depression and factitious disorder: a new presentation. AB - This article discusses a presentation of Munchausen Syndrome by Proxy. It is believed this factitious disorder was precipitated and grew out of the context of a postpartum depression. To our knowledge, no such case has been reported in the past and implications for new exclusion criteria defining a fictitious disorder are raised. Furthermore, reintegration of the perpetrator back to family is discussed and suggestions are made for follow-up. PMID- 11209996 TI - Alpha-vascular responses after short-term and long-term inhibition of nitric oxide synthesis. AB - Apart from the direct actions of nitric oxide (NO) on vascular smooth muscle, this factor may regulate cardiovascular functions through specific actions on alpha-adrenergic constrictor mechanisms. In this study we aim to establish whether the inhibition of the synthesis of this mediator could alter the vasoconstrictor responses mediated by alpha-adrenoceptor stimulation. We have been able to demonstrate that the blockage of the NO synthase really does exist, when both short- and long-term treatments with Nomega-nitro-Larginine methyl ester (L-NAME) are carried out. We have evaluated the concentration-dependent contractions induced by the selective alpha1-adrenoceptor agonists methoxamine and phenylephrine in isolated rat aorta rings in the following groups of animals: control, short-term L-NAME-treated (100 mg/kg i.p. 20 min before subjecting the animals to the experiments) and long-term L-NAME-treated (100 mg/kg per day in the drinking water for 7, 21, or 45 days). We have also evaluated the pressor responses to methoxamine and to the selective alpha-adrenoceptor agonist B-HT 920 using the pithed rat preparation in the same groups of animals. The contractile responses to methoxamine and phenylephrine were similar in the rat aorta preparations from control and short-term L-NAME-treated animals. On the contrary, in the rat aorta preparations from long-term L-NAME-treated animals these responses were clearly reduced when compared with the corresponding responses in those from control animals, the reduction being more marked when the treatment lasted longer. The pressor responses to methoxamine were also similar in control and short-term L-NAME-treated pithed rats. Nevertheless, the responses to B-HT 920 were greater in the latter. On the other hand, the dose-response curves to both alpha-adrenoceptor agonists were shifted to the right in a non-parallel manner in rats treated long term with L-NAME, the shift being, in the case of B HT 920, more accentuated when the treatment lasted 21 or 45 days than when it lasted only 7 days. These results indicate that the short-term decrease in NO synthesis does not modify the vascular smooth muscle responses mediated by alpha1 adrenoceptor stimulation, but it does induce a potentiation of sympathetic vasoconstriction mediated by alpha2-adrenoceptors. Nevertheless, the long-term inhibition of NO synthesis causes a compensating decrease in the alpha1- and alpha2-vascular smooth muscle contractile responses. PMID- 11209997 TI - Protective effect of SM-20550, a selective Na+ - H+ exchange inhibitor, on ischemia-reperfusion-injured hearts. AB - The protective effects of Na+ - H+ exchange inhibitors SM-20550 (SM) and 5-(N ethyl-N-isopropyl)-amiloride (EIPA) against ischemia-reperfusion injury were investigated in guinea pig Langendorff hearts. The changes in intracellular pH (pHi), high-energy phosphates, and biologic intracellular active ions ([Na+]i and [Ca2+]i) were regarded using the 31P-NMR and specific fluorescent signals from the heart tissues together with simultaneous recordings of the left ventricular developed pressure (LVDP). The recovery rate of LVDP from ischemia (40 min) by reperfusion was 36.8% in the control experiments, whereas in the presence of SM 10(-7) M, a gradual increase to 75.9% (55.5% with 10(-8) M), in contrast to EIPA (10(-7) M), 47.5% was observed. SM 10(-7) M restored the ATP level by 70% in 40 min reperfusion, which was already higher than the control in the latter half (20 40 min) of the ischemic period. The recovery rate of phosphocreatine by pretreatment of the heart with SM 10(-7) M was 75% in 40 min reperfusion. The pHi estimated from Pi/phosphocreatine chemical shift became highly acidic in ischemic heart so that SM 10(-7) M caused slight but significant pHi reduction from control pHi of 5.89 to 5.75. The level returned to pHi at around 7.38 during 30 40 min reperfusion, and the recovery was significantly greater than the control pHi of 7.24. The fura-2 Ca2+ or SBFI-Na+ signals during Langendorff ischemia heart increased, and rapidly returned to the control level after the reperfusion. SM suppressed the [Na+]i or [Ca2+]i elevation induced in the late stage during ischemia, resulting in LVDP restoration after reperfusion; Diastolic Ca2+ in the end period of ischemia, SM 10(-7) M 194% versus drug-free 220.7%. Na+: SM 10(-7) M 121.6% versus drug-free 128.0%. The present results suggest that the selective Na+ - H+ exchange inhibitor SM is promising as a potent and specific protective agent against ischemia-reperfusion injuries with Ca2+ overload induced via Na+ - H+, Na+ - Ca2+ exchange. PMID- 11209998 TI - Suppression of cell proliferation by tissue plasminogen activator during the early phase after balloon injury minimizes intimal hyperplasia in hypercholesterolemic rabbits. AB - Thrombus formation is a key component of the pathogenesis of restenosis after arterial balloon injury. The purpose of this study was to determine whether intimal hyperplasia could be attenuated by infusion of recombinant tissue plasminogen activator (tPA). Forty-two Kurosawa and Kusanagi hypercholesterolemic rabbits were divided into tPA (n = 20) and control (n = 22) groups, the former receiving 7 days of continuous tPA infusion (0.6 mg/kg/day) via ear veins. The walls of the common iliac arteries were injured using 2.5-mm balloon catheters and then examined histologically 7, 14, 21, and 28 days later. Cell proliferation was assessed by immunohistochemical analysis of proliferating cell nuclear antigen (PCNA), and transforming growth factor (TGF)-beta immunohistochemistry was carried out to estimate cell proliferation and differentiation. It was observed that 28 days after balloon injury, intimal cross-sectional areas in the tPA group were significantly smaller than in controls (0.11 +/- 0.03 mm2 vs. 0.57 +/- 0.08 mm2, p < 0.01), as were ratios of the cross-sectional areas of the intima and media (0.21 +/- 0.07 vs. 1.06 +/- 0.18, p < 0.05). In addition, the numbers of PCNA-positive medial cells were significantly lower (0.06 +/- 0.01 vs. 0.36 +/- 0.08, p < 0.05) and TGF-beta-positive vessel wall areas were significantly smaller in tPA-treated animals 7 days after balloon injury (0.47 +/ 0.28% vs. 4.55 +/- 1.44%, p < 0.05). Thus infusion of tPA after arterial balloon injury appears to decrease medial cell proliferation and suppress intimal hyperplasia. PMID- 11209999 TI - Renin-angiotensin system contribution to cardiac hypertrophy in experimental hyperthyroidism: an echocardiographic study. AB - The objective of this study was to evaluate, using echocardiography, the involvement of the renin-angiotensin system (RAS) in left ventricular (LV) hypertrophy development in experimental hyperthyroidism. Thyrotoxicosis was produced by a daily intraperitoneal injection of L-thyroxine (T4), 0.1 mg/kg per day for 15 days in Wistar rats. Control (euthyroid) rats received intraperitoneal daily injection of the thyroxine solvent. Two series of experiments were performed. In the first series, euthyroid (n = 10) and hyperthyroid (n = 14) rats were surgically prepared with a femoral artery catheter. After a 3-day recovery period, blood pressure and heart rate were measured and blood samples were collected in conscious and unrestrained rats. In the second series of experiment, measurement of LV geometry was realized with two-dimensional time-movement echocardiography on the 15th day of treatment in control conditions and after long-term treatment with the angiotensin II type I receptor antagonist valsartan (10 mg/kg per day for 15 days) in both euthyroid and hyperthyroid rats. The dose and duration of T4 treatment was sufficient to induce a significant degree of hyperthyroidism with characteristic features including tachycardia, systolic hypertension, myocardial hypertrophy, hyperthermia, and weight loss. In addition, we measured an increase in free fractions of thyroid hormones, and a threefold increase in plasma renin activity. Echocardiographic examinations in rats revealed a strong correlation between LV weight and echocardiographic LV mass. Hyperthyroid rats exhibited an increased LV mass with a marked increase in the LV end-diastolic posterior wall and septal thickness. Chronic treatment with valsartan prevented this concentric LV hypertrophy (p < 0.01), with full prevention of the LV posterior wall hypertrophy (p < 0.001) and decreased LV septal hypertrophy (p < 0.05). In conclusion, the cardiovascular alterations of hyperthyroidism were reproduced with thyroid hormone injections in rats. Activation of the RAS in hyperthyroid rats was accompanied by increased LV mass. Using valsartan, we demonstrated that the RAS impinged on the LV remodelling in our experimental hyperthyroidism model. A chronic treatment with an angiotensin II type I receptor antagonist prevented the development of the concentric LV hypertrophy associated with thyrotoxicosis. PMID- 11210000 TI - On the mechanisms of cholinergic control of the sinoatrial node discharge. AB - It has been proposed that cholinergic agonists inhibit the sinoatrial node discharge by shifting the activation range of the hyperpolarization-activated inward current If to more negative values or by increasing potassium conductance. In the former instance, cesium will potentiate the cholinergic inhibition by blocking any residual If; in the latter instance, Cs+ and Ba2+ will antagonize the inhibitory action by blocking K+ channels. The changes in discharge induced by high and low concentrations of carbachol were studied using an electrophysiologic technique in isolated guinea pig sinoatrial node perfused in vitro in the absence and presence of different concentrations of Cs+ and Ba2+. In Tyrode solution, high carbachol concentrations (0.5-2 microM) slowed the sinoatrial node by hyperpolarizing the membrane and by reducing the amplitude of diastolic depolarization; and stopped the sinoatrial node by preventing the attainment of threshold potential. Adding Cs+ (10 mM) to carbachol increased the rate in slowly discharging sinoatrial node and induced spontaneous discharge in quiescent sinoatrial node. In high [K+]o (approximately 12 mM), carbachol slowed or stopped the slow responses and adding Cs+ accelerated or induced discharge. Both in Tyode and in high [K+]o, in the presence of Cs+, carbachol did stop the sinoatrial node. In the presence of carbachol, Ba2+ (0.1 mM) accelerated or induced discharge, as Cs+ did. Atropine (1 microM) prevented both the slowing or suppression by carbachol and the acceleration of sinoatrial node by Cs+ in the presence of carbachol. Low carbachol concentrations (0.05-0.1 microM) decreased the rate to a similar extent in the absence and the presence of a low concentration of Cs+ (2 mM, which blocks If but not K+ channels), but markedly less in the presence of 0.5-0.75 mM Ba2+ (which block K+ channels but not If). We conclude that cholinergic agonists slow or stop the sinoatrial node by a shifting the membrane potential toward the more negative subsidiary pacemaker range and away from the threshold. The results with Cs+ and Ba2+ indicate that both high and low concentrations of carbachol decrease sinoatrial node discharge by activating the I(K,ACh) channels rather than by decreasing If. PMID- 11210001 TI - Factors affecting endothelin-induced venous tone in conscious rats. AB - There may be a relation between altered venous function, endothelin (ET)-1, and an impairment in the activity of endothelial-derived nitric oxide (NO) and prostanoids in salt-dependent hypertension. The present study examined the effects of salt intake on ET-induced changes in venomotor tone and the effects of blockade of NO synthase with N(G)-nitro-L-arginine methyl ester (L-NAME) and of cyclooxygenase with indomethacin on venomotor tone caused by the ET(B) selective agonist sarafotoxin 6c (S6c) in awake rats. Rats were anesthetized for permanent placement of catheters for measurements of arterial and venous pressures. A silicone balloon catheter was also fixed in the right atrium to produce brief circulatory arrest. Venomotor tone was estimated from measurements of mean circulatory filling pressure (MCFP) in conscious rats. There were no differences in mean arterial pressure, heart rate, or MCFP responses to short-term administration of ET-1 or S6c at different levels of salt intake. L-NAME or indomethacin did not change MCFP or the response of MCFP to short-term injection of S6c. In conclusion, neither basal MCFP nor integrated venomotor responses to short-term injection of ET-1 or S6c were altered by short-term changes in salt intake, blockade of NO synthase or cyclooxygenase. These data do not support the hypothesis that increased salt intake alters reactivity of veins to ET-1, NO, or prostanoids. PMID- 11210002 TI - Effects of acute global low-flow ischemia on triggered arrhythmias in d-sotalol induced long Q-T intervals in perfused rabbit hearts. AB - Little information is available on how acute ischemia modifies the electrophysiologic substrate associated with long Q-T interval conditions. We studied the effects of low-flow ischemia (10 min at 5.0 ml/min followed by 10 min of 2.5 ml/min) in Langendorff perfused rabbit hearts during control and in hearts 20 min after the addition to the perfusate of 92 microM d-sotalol, which reliably produced triggered activity. Epicardial electrograms, a left ventricular endocardial monophasic action potential (MAP), and simulated X and Y lead electrocardiograms were used to characterize myocardial activation and recovery during ventricular pacing. In the control hearts, conduction velocity as indicated by the mean epicardial activation time accelerated for most of the period of ischemia (maximum decrease of -9.4 +/- 7.9%). The mean activation recovery interval, MAP duration, and Q-T interval were moderately decreased (-4.9 +/- 8.6%, -7.5 +/- 4.4%, and -4.6 +/- 2.3%, respectively). The mean standard deviation of the activation-recovery interval (epicardial heterogeneity of recovery) was increased by 34.6 +/- 23.4%. d-Sotalol had no effect on conduction but prolonged myocardial recovery time, increased heterogeneity, and produced triggered arrhythmias in all hearts. Within 2 min of ischemia triggered activity was eliminated. With d-sotalol, ischemia slowed conduction and produced relatively larger decreases in the activation-recovery interval, MAP duration, and Q-T interval (-11.8 +/- 10.3%, -13.9 +/- 12.0%, and -15.8 +/- 11.2%). The increased epicardial heterogeneity seen with d-sotalol was attenuated by ischemia. Thus ischemia superimposed on long Q-T conditions had antiarrhythmic as well as arrhythmogenic effects. PMID- 11210003 TI - Increase in myofibrillar Ca2+ sensitivity induced by UD-CG 212 Cl, an active metabolite of pimobendan, in canine ventricular myocardium. AB - We performed experiments in canine ventricular trabeculae loaded with aequorin to elucidate the mechanism of positive inotropic effect of UD-CG 212 Cl (4,5-dihydro 6-[2-(4-hydroxyphenyl)-1H-benzimidazole-5-yl]-5-methyl-3(2H)-pyridazinone), an active metabolite of pimobendan. The maximum response to UD-CG 212 Cl achieved at 10(-5) M was 18% of ISOmax and it was associated with an increase in Ca2+ transients of 7% of ISOmax. For a given increase in force, the increase in Ca2+ transients induced by UD-CG 212 Cl was less than that induced by elevation of [Ca2+]o. The positive inotropic effect of UD-CG 212 Cl was not associated with an impairment of relaxation and it was abolished by carbachol. In conclusion, UD-CG 212 Cl has a positive inotropic effect partly due to an increase in myofibrillar Ca2+ sensitivity that is exerted via cross talk with a signal transduction pathway that involves cAMP. PMID- 11210004 TI - Transforming growth factor-beta regulation of endothelin expression in rat vascular cell and organ cultures. AB - Transforming growth factor (TGF)-beta increases the production of the vasoactive peptide endothelin (ET) in cultures of vascular endothelial cells (EC) and vascular smooth muscle cells (VSMC), but the physiologic or pathologic significance of this regulation has not been determined. The present studies test the hypothesis that when EC and VSMC are in direct contact or close proximity, ET expression is, at least in part, dependent on TGF-beta. The effects of TGF-beta on ET-1 mRNA (Northern analysis and reverse transcription polymerase chain reaction) and peptide (radioimmunoassay) levels were assessed in rat EC and VSMC and vascular organ cultures. TGF-beta2 (1 ng/ml) increased ET-1 mRNA in VSMC and EC plus VSMC cultures and increased ET-1 peptide in EC, VSMC, and EC plus VSMC cultures. TGF-beta2 also increased ET-1 mRNA and peptide in vascular organ cultures. Antibodies that neutralized the activities of TGF-beta1 and TGF-beta2 decreased ET-1 mRNA in EC plus VSMC cultures and in vascular organ cultures. These data indicate that when EC and VSMC are in direct contact or close proximity, TGF-beta increases ET expression and active TGF-beta is present and promotes ET expression. These data suggest that TGF-beta is a determinant of vascular ET expression in vivo, and that TGF-beta regulation of ET expression would affect cardiovascular function in health and disease. PMID- 11210005 TI - Different contribution of endothelial nitric oxide in the relaxation of human coronary arteries of ischemic and dilated cardiomyopathic hearts. AB - Coronary artery disease and congestive heart failure (CHF) have been associated with a reduction in nitric oxide (NO) release or bioavailability from the vascular endothelium. The objectives of this study were to compare the role of NO in human coronary vessels isolated from nonischemic dilated (DCM) (n = 10) and ischemic (ICM) (n = 12) cardiomyopathic hearts. Segments were mounted on a wire myograph to record changes in isometric tension. All experiments were performed in the presence of indomethacin (10 microM). Contractions induced by angiotensin II (0.1 microM) or a depolarizing physiologic solution containing 40 mM KCl, were of similar amplitude in DCM and ICM. In vessels precontracted with angiotensin II, acetylcholine (1 microM) caused an endothelium-dependent relaxation of rings from DCM but a paradoxical contraction of rings from ICM; NO synthase inhibition with Nomega-nitro-L-arginine (L-NNA, 100 microM) did not affect acetylcholine induced relaxation or contraction of DCM or ICM vessels, respectively. By contrast, substance P (0.1 microM) induced an endothelium-dependent relaxation in both groups of vessels; this relaxation was prevented (p < 0.05) by L-NNA in vessels from ICM hearts but only reduced (p < 0.05) by L-NNA in vessels from DCM hearts. In depolarized conditions, acetylcholine contracted (p < 0.05) whereas substance P induced a complete relaxation (p < 0.05) of vessels from both groups: substance P-induced relaxation was abolished (p < 0.05) by L-NNA. Our data suggest that in the presence of indomethacin, NO does not contribute to acetylcholine-induced relaxation of human epicardial coronary arteries isolated from DCM hearts. Furthermore, whereas NO and a secondary endothelium-derived relaxing factor sensitive to high K+ contribute to substance P-induced relaxation of rings from DCM hearts, only NO is involved in ICM hearts. PMID- 11210006 TI - Time trends of occupational pesticide-related injuries in Costa Rica, 1982-1992. AB - To evaluate time trends of occupational pesticide-related injuries in Costa Rica, a survey was carried out three times over a ten-year period at a national reporting system for occupational accidents and diseases among wage-earning workers. The sample comprised the accidents reported during the months of June of the years 1982, 1987, and 1992. The overall incidence rates were 1.8, 2.7, and 2.5 per 1,000 agricultural workers, respectively. Rates among female workers increased (3.1, 3.7, 5.4) and were elevated as compared with male workers (1.7, 2.6, 2.3). The trend for topical lesions was upgoing (1.2, 1.4, 2.1), consistent with an increased use of fungicides and lack of safety measures for pesticides with low acute toxicity. Systemic poisonings peaked in 1987 (0.6, 1.2, 0.5), declining in 1992 with increased use of biologic pest control and pyrethroid insecticides less toxic than cholinesterase inhibitors, and improved safety during nematocide applications on banana plantations. In 1992, despite the largest decline of systemic poisonings in the banana-producing Atlantic Region, poisonings as well as topical injuries were still four times more frequent in this region than in the rest of the country. Restriction of highly toxic pesticides together with implementation of occupational safety measures can reduce systemic poisonings in developing countries. Such policies need to be extended to other pesticides to prevent less life threatening but often disabling skin and eye injuries. PMID- 11210007 TI - Use of an asbestos exposure score and the presence of pleural and parenchymal abnormalities in a lung cancer case series. AB - To assess whether there was an association between asbestos exposure and abnormalities on chest x-rays or CT scans, chest radiographs and CT scans of 103 asbestos-exposed patients with known lung cancer were reviewed for pleural or parenchymal abnormalities. Asbestos exposure was assessed using an asbestos exposure index that integrated time and intensity of reported exposure via a weighting scheme. Chest CT scans were clearly more sensitive in detecting pleural or parenchymal abnormalities than were standard PA chest x-rays. Furthermore, there was a significant correlation between higher asbestos exposure index scores and abnormalities on CT scans. Multivariable logistic regression models were used to investigate the relationship between the asbestos exposure index score and pleural or parenchymal abnormalities after adjusting for gender, pack-years of smoking, and cell type. None of these variables was associated with abnormalities on chest x-rays or CT scans. An asbestos exposure score > 10 was associated with pleural or parenchymal abnormalities (OR = 4.93; 95%CI 1.05-23.12). The results suggest that assessment of asbestos exposures by means of an algorithm-based index can classify the exposures accurately for epidemiologic studies. PMID- 11210008 TI - Pulmonary function of workers exposed to ammonia: a study in the Eastern Province of Saudi Arabia. AB - To determine the effect of chronic exposure to ammonia on pulmonary function among ammonia workers, 77 workers were randomly selected from an ammonia factory in the Eastern Province of Saudi Arabia and 355 were selected as controls from the administrative staffs of four industrial groups in Eastern Province. Spirometry was carried out and FEV1, FVC, and FEV1/FVC% were calculated. The ammonia level in the working environment was determined spectrophotometrically. 30% of the air samples had ammonia concentrations that exceeded the threshold limit value. Significant reductions in FEV1 % predicted and FVC % predicted were observed in ammonia workers exposed to higher cumulative ammonia levels (above 50 mg/m3-years). FEV1% predicted and FEV1/FVC% were significantly lower in symptomatic than in asymptomatic workers in the exposed group. These findings may raise the possibility that exposure to a high cumulative ammonia level produces a combined restrictive/obstructive ventilatory defect. PMID- 11210009 TI - Health effects of occupational exposures to vehicle emissions in Shanghai. AB - The authors investigated the health effects of occupational exposures to vehicle emissions in 745 bus drivers, conductors, and taxi drivers, compared with 532 unexposed controls, in Shanghai. Logistic regression and general linear models were used to examine the relationship between exposure and respiratory illness. Results showed that the prevalences of some respiratory symptoms and chronic respiratory diseases were significantly higher (p < 0.05) in the exposed group than in the controls. The adjusted odds ratios for throat pain, phlegm, chronic rhinitis, and chronic pharyngitis were 1.95 (95% CI 1.55-2.46), 3.90 (95% CI 2.61 5.81), 1.96 (95% CI 1.11-3.46), and 4.19 (95% CI 2.49-7.06), respectively. Also, there were exposure time response relationships for the prevalences of phlegm and chronic respiratory disease. Pulmonary function and blood lead levels were not significantly correlated with exposure status. The results suggest that occupational exposure to vehicle emissions may induce detectable adverse health effects. PMID- 11210010 TI - Worksite and personal factors associated with carpal tunnel syndrome in an Egyptian electronics assembly factory. AB - The study objective was to identify personal and work-related risk factors associated with carpal tunnel syndrome (CTS) in electronics assembly, operators relative to clerical workers in the same factory. Of 422 workers in a television assembly factory located in Ismailia, Suez Canal Area, Egypt, 198 (46.9%) participated. The electronics assembly workers were more likely to report CTS (odds ratio = 11.41, 95% CI = 3.6 -40.26) than were the clerical workers. The significant risk factors were longer work years (odds ratio = 1.11, 95% CI = 1.03 1.20) and precision-type hand grip (odds ratio = 6.5, 95% CI = 1.08-39.23). The results suggest an association between electronics assembly and CTS. Work years and precision grip are possible risk factors for CTS and should be studied more thoroughly. Tools to reduce the need for precision grip may help reduce CTS. PMID- 11210011 TI - Pediatric environmental health: perceptions from a survey questionnaire. AB - To expand the base of knowledge regarding perceptions about potential environmental threats to children's health, a survey was conducted in the Northwest United States. Samples of Head Start parents, PTA presidents, public health officials, school nurses, naturopathic physicians, family practitioners, and pediatricians were mailed a questionnaire inquiring into the nature and degree of concerns about pediatric environmental health. The response rate was 24%. Trends in the data showed disparities in perceptions regarding levels of concern and exposure concerns between respondent categories. Disparities also existed regarding information resources used for children's environmental health. Recognizing differences in perceptions of children's environmental health, as demonstrated in these results, may be useful for risk communication and resource allocation, especially in the context of the wide variety of health belief models. Such knowledge may help clarity situations with environmental health risk concerns, including clinical, public health, and educational circumstances. PMID- 11210012 TI - Household firewood use and the health of children and women of Indian communities in Chiapas, Mexico. AB - A follow-up study in two rural communities in the state of Chiapas, Mexico, compared families that used an improved stove for cooking with those that used traditional open-fire stoves, to assess the risks of respiratory symptoms in children and women exposed to wood smoke. 16-hour measurements showed that the concentration of particles less than 10 microm in diameter was significantly lower in households with the better stoves in the kitchen area, where children usually play, i.e., 158 microg/m3 vs 305 microg/m3 (p = 0.03). Multivariate models showed that using the better stove tended to protect against symptoms such as the common cold in children (RR 0.24; 9.5% CI 0.05, 1.02). Use of more firewood was linked to greater risks of experiencing difficulty breathing (RR 1.15; 95% CI 1.04, 1.27) and the common cold (RR 1.09; 95% CI 1.01, 1.18) in women. The use of stoves that require less wood for cooking reduces the risks of respiratory symptoms that may contribute to complicated respiratory diseases and mortality. PMID- 11210013 TI - Silicosis and tuberculosis: Part 2--a radiographic presentation of nodular tuberculosis and silicosis. AB - Indolent nodular pulmonary tuberculosis (TB) in workers exposed to silica dust may go undetected clinically and radiographically, especially in the absence of identification of tubercle bacilli in sputum. Illustrative cases demonstrating the radiographic manifestations of coexistent pulmonary silicosis and the indolent form of nodular TB are presented. Alterations in the usual chronologic progress, a rapid advance in nodular profusion or size outside the expected time frame, and distinct pattern alterations are features indicating the presence of TB associated with silicosis. PMID- 11210014 TI - Methodologic considerations in estimating burden of disease from environmental risk factors at national and global levels. AB - Evidence from environmental burden-of-disease studies can provide valuable input in the decision-making process in environmental health, facilitating priority setting and cost effectiveness evaluation. This paper discusses important aspects of environmental burden-of-disease estimates in the light of) published examples. To produce reliable and comparable burden-of-disease estimates for environmental and occupational risk factors, harmonized methods are needed. Such methods should address the feasibility of data collection at national, regional, and global levels, the reliability of estimates, the uncertainty around estimates, and scenario tools to investigate the health gains of options for preventive action in different domains of policy. Any such method will require a framework (i.e., causal inference model) able to take into account the contributions of distal and proximal causes, and the possible interactions between risk factors. PMID- 11210015 TI - Efforts to stop repression bias by protecting whistleblowers. PMID- 11210016 TI - Cardiovascular effects in viscose rayon workers exposed to carbon disulfide. AB - The objectives of this study were to investigate the cardiovascular effects in workers currently exposed to carbon disulfide (CS2) below the threshold limit value (TLV) of 31 mg/m3 and to determine the prevalence of coronary heart disease (CHD) after long-term exposure. 172 men (91 workers exposed to CS2 in a viscose rayon factory and 81 referent workers) were examined using a medical and job history questionnaire, Rose's questionnaire, and electrocardiography at rest, and by measuring blood pressure and serum lipids and lipoproteins. Personal exposures were monitored simultaneously with active sampling and findings were analyzed according to the NIOSH 1600 method. As a result of technical and organizational improvements, personal CS2 exposures were well below the TLV (5.4-13.02 mg/m3). No significant effect of CS2 on blood pressure or lipids (total cholesterol, HDL and LDL cholesterol, triglycerides, and apolipoproteins AI and B) was found, even after allowance for confounding factors. The prevalence of CHD (ECG abnormalities and chest pain) was higher in the viscose rayon workers than in the workers with no exposure but reached statistical significance for men with exposure histories often years and more only (cumulative CS9 index > or = 150 mg/m3, the most highly exposed group). The findings suggest that the coronary risk is increased in workers previously exposed to high CS2 concentrations but not in those exposed to CS2 levels below the current TLV. PMID- 11210017 TI - Water contamination: a legacy of the union carbide disaster in Bhopal, India. PMID- 11210018 TI - Phase two responds to the HSE request. PMID- 11210019 TI - Fluid dairy product quality and safety: looking to the future. AB - The fiercely competitive nature of the US beverage industry will drive the fluid milk sector of the dairy industry to improve product quality and shelf life to enable dairy beverages to compete with innovative new introductions as well as with currently popular shelf-stable products. The recent substantial growth in the volume of flavored milk sales specifically suggests that attention is needed to improve these products. Further, increasing public awareness and regulatory attention directed toward food safety issues highlight the need for the dairy industry to proactively address and eliminate emerging food safety issues that may negatively impact the image of dairy products. Shelf life and sensory profiles of high temperature short time pasteurized fluid milk products are presented, illustrating the need for greater attention to controlling contaminating microorganisms in processed fluid milk products. Bacterial spoilage patterns of flavored versus unflavored milks are compared, and suggestions are presented for extending flavored product shelf lives. Strategies currently applied to extend shelf life are reviewed. Food safety issues facing the dairy industry are presented within the context of an overview of foodborne illnesses in the United States. The pressing need to determine thermal resistance characteristics of Mycobacterium paratuberculosis is described. PMID- 11210020 TI - Effect of composition of colostrum and transition milk from Holstein heifers on specificity rates of antibiotic residue tests. AB - The objective of this study was to evaluate the effects of colostrum and transition milk composition on specificity rates of antibiotic residue screening tests. Milk from 25 primigravid Holstein heifers was collected from either first, second, or third milking (colostrum) and from either fifth, sixth, or seventh milking (transition milk) following parturition. Milk sampled was visibly normal and heifers were not treated with an antibiotic within 30 d before parturition. Quarter foremilk samples were collected aseptically and analyzed for mastitis pathogens. A sample from the total composite milk was analyzed for somatic cell counts (SCC), milk protein and fat, immunoglobulin concentrations and for antibiotics using four antibiotic residue screening tests. Mastitis pathogens were present in colostrum from 36% of heifers (n = 9) and from 16% of heifers (n = 4) in the subsequent transition milk. Mean SCC were 2,458,000 and 866,000 counts/ml and IgG1 concentrations were 22.7 and 3.07 mg/ml for colostrum and transition milk, respectively. Specificity rates of the screening tests ranged from 0.16 to 0.88 for colostrum and 0.60 to 1.0 for transition milk. Increased milk protein and IgG1 concentrations in milk were associated with an increase in the probability of a false positive outcome for the Charm Cowside (Charm Sciences, Inc., Malden, MA), CITE Snap (IDEXX Laboratories, Westbrook, ME), and Penzyme (Cultor Food Science, Milwaukee, WI) tests. Fat content of milk was positively related to an increase in false positive rates for the CITE Snap test. Milk should not be tested for antibiotic residues before the sixth milking after parturition to avoid high rates of false positive outcomes. PMID- 11210021 TI - Factors associated with milk urea concentrations in Ontario dairy cows. AB - All DHI test-day data, including milk urea concentrations measured by infrared test method, were collected from 60 commercial Ontario Holstein dairy herds for a 13-mo period between December 1, 1995, and December 31, 1996. The objectives of this study were to describe the relationships between milk urea concentrations and seasonal factors, sampling factors, cow factors, and test-day production of milk, milk fat, protein, and SCC. Milk urea was associated with month and season; concentrations were the highest from July to September. Milk urea was generally lower in first-lactation cows. Milk urea was lowest during the first 60 d of lactation, higher between 60 and 150 d in milk, and lower after approximately 150 d in milk. In herds on an alternating a.m./p.m. test schedule, milk urea was generally lower in a.m. than p.m. tests. There was a positive nonlinear association between milk urea and milk yield, fat-corrected milk, and energy corrected milk. There was a negative nonlinear association between milk urea and both milk fat and total protein percentages. While there was a negative nonlinear association between cow-level milk urea and linear score, the study found no association between herd average milk urea and herd average linear score. The associations described in this study using Dairy Herd Improvement test-day samples from commercial dairy herds and using an infrared test to measure milk urea are generally consistent with results from studies that used individual animals housed under research conditions and chemical methods to measure milk urea. Because milk urea varies by season, month, parity group, stage of lactation, and sample type, studies should control for these variables. Because of the apparent effect of a.m. and p.m. sampling on urea concentration, producers on an alternating a.m./p.m. test schedule should test routinely to establish a herd pattern for urea and submit the same sampling time consistently or both. PMID- 11210022 TI - Peripartum responses of dairy cows fed energy-dense diets for 3 or 6 weeks prepartum. AB - Pregnant cows (n = 189) in two commercial dairy farms were assigned randomly to be fed energy-dense diets for either 3 or 6 wk before expected calving. Cows fed diets for less than or equal to 26 d were designated the short (S) treatment group, and those fed greater than 26 d were the long (L) treatment group. Cows in L tended to have improved energy status during the first 2 wk postpartum, as indicated by higher insulin concentrations and a tendency for lower nonesterified fatty acid concentrations. Treatment did not affect plasma beta-hydroxybutyrate concentrations. Cows in L tended to gain more body condition during the late dry period. Total body condition loss from parturition through 6 wk postpartum was not different between treatments, but the rate of change varied over this period. Cows in S lost more body condition during the first 3 wk postpartum than cows in L. In farm 1 only, cows in L lost more body condition from 3 to 6 wk postpartum and had a higher incidence of metritis and a longer interval to first service than cows in S. Cows in L had higher milk protein content through 60 d in milk compared with cows in S. Additionally, cows in L in farm 1 produced 4.4 kg/d less milk, tended to have lower milk fat content and yields, and higher somatic cell counts through 150 d in milk than cows in S. Overall, increasing the length of time cows were fed the energy-dense diet prepartum elicited significant changes in farm 1, but had little effect in farm 2. Based on these results, L treatment may improve energy status immediately postpartum, but long-term effects varied between farms, perhaps due to other unmeasured management differences. PMID- 11210023 TI - Quantitative descriptive analysis and principal component analysis for sensory characterization of ultrapasteurized milk. AB - Quantitative descriptive analysis was used to describe the key attributes of nine ultrapasteurized (UP) milk products of various fat levels, including two lactose reduced products, from two dairy plants. Principal components analysis identified four significant principal components that accounted for 87.6% of the variance in the sensory attribute data. Principal component scores indicated that the location of each UP milk along each of four scales primarily corresponded to cooked, drying/lingering, sweet, and bitter attributes. Overall product quality was modeled as a function of the principal components using multiple least squares regression (R2 = 0.810). These findings demonstrate the utility of quantitative descriptive analysis for identifying and measuring UP fluid milk product attributes that are important to consumers. PMID- 11210024 TI - Potential for milk containing penicillin G or amoxicillin to cause residues in calves. AB - The potential for antibiotic residues in calves from consuming milk containing penicillin G or amoxicillin was investigated. Six calves were fed milk replacer, 6% body weight twice daily, containing 0.293, 2.92, or 5.85 microg of penicillin/ml (ppm) G or 0.25, 1.0, or 2.0 microg of amoxicillin/ml for three consecutive feedings. Urine and blood samples were collected after each feeding. Serum and urine samples were tested with a microbial receptor assay and a microbial growth inhibition assay to indicate potential drug residues. Penicillin G and amoxicillin were detected in the serum and urine of several calves 3 h after drinking spiked milk replacer. Possible violative drug residues in the calves were detected by the microbial growth inhibition assay up to 15 h after drinking spiked milk replacer. Penicillin G, but not amoxicillin, could be detected in urine 24 h after the final feeding of spiked milk replacer. Subsequently, six calves were fed milk replacer containing 11.7 microg of penicillin G/ml (ppm) twice daily, 6% body weight per feeding. Calves were slaughtered 3 h after the final feeding. Mean (+/-SD) concentrations of penicillin G measured by high-pressure liquid chromatography in liver, kidney, muscle, and serum were 0.409 (+/-0.167) microg/g, 0.031 (+/-0.012) microg/g 0.008 (+/-0.002) microg/g, and 0.013 (+/-0.006) mg/ml, respectively. This study indicates that calves fed milk with amoxicillin or penicillin G could possibly have violative residues if slaughtered within 24 h after feeding. Violative drug residues in liver tissue were found in calves slaughtered 3 h after consuming milk replacer containing 11.7 microg of penicillin G/ml (ppm). PMID- 11210025 TI - Plasma ascorbate concentrations are not correlated with milk somatic cell count and metabolic profile in lactating and dry cows. AB - The purpose of this study was to determine the effects of stage and the number of lactation on plasma ascorbate concentration and to establish the association between plasma ascorbate concentrations and plasma glucose, insulin, nonesterified fatty acids (NEFA), beta-hydroxybutyrate (BHBA), aspartate aminotransferase (AST), milk somatic cell count (SCC), milk yield, and body condition score (BCS) in dairy cows. Holstein cows (n = 193) from three different herds were used in this study. Animals were randomly selected, and assigned to five groups according to stage of lactation (group 1, dry cows; group 2, 1 to 28 d; group 3, 29 to 56 d; group 4, 57 to 140 d; group 5, 141 to 280 d), and the number of lactation (primiparous or multiparous). Plasma ascorbate concentration, plasma glucose concentration, serum insulin concentration, plasma NEFA concentration, plasma BHBA concentration, serum AST concentration, milk SCC, milk yield, and BCS were measured. The results of this study demonstrate that plasma ascorbate concentrations do not change in response to stage of lactation, or number of lactations. Among the several variables studied, none was found that, singly or in combinations, could explain variations in ascorbic acid concentrations. PMID- 11210026 TI - Is intersucking in dairy cows the continuation of a habit developed in early life? AB - Intersucking, i.e., cattle sucking the udder of heifers or cows, is a frequent problem in dairy herds and may lead to udder damage, mastitis, milk loss, and culling of breeding animals. Using epidemiological methods, we conducted an observational cross-sectional study to investigate risk factors for intersucking in Swiss dairy cows. We asked 114 randomly selected dairy farmers about a broad spectrum of environmental factors possibly associated with intersucking, such as housing conditions, management, and feeding of calves, heifers, and cows. Thirty of the 114 farms were confronted with intersucking in cows. The mean proportion of intersucking cows per farm was 1.6%. From a total of 3077 cows (Swiss Brown Cattle, Simmental, and Holstein Friesian) we recorded 49 cows that had performed or were currently intersucking. In 69% of these cows, intersucking had been observed as heifers. Using path analysis and multivariable stepwise backward logistic and linear regression analyses, we revealed that the most important risk factor for intersucking cows was the presence of intersucking heifers on a farm (odds ratio = 7.8). The results suggest that intersucking in cows is the continuation of a habit that was already established in a cow's subadult life. This emphasizes the importance of looking not only at the animal's current environmental situation but also considering its entire life history for the prevention of behavioral problems. PMID- 11210027 TI - The effect of cation-anion difference on calcium requirement, feed intake, body weight gain, and blood gasses and mineral concentrations of dairy calves. AB - Our objective was to examine the effects of two diets with different cation-anion differences on Ca requirements in the growing calf. Holstein calves (n = 48, 24 males) were blocked at 56 to 70 d after birth (80+/-10 kg of body weight) according to sex and birth date and assigned randomly in a 2 x 3 factorial arrangement of dietary treatments containing cation-anion differences as meq (Na + K) - (Cl + S)/kg of diet dry matter and Ca content of 1) 0 and 0.35%, 2) 0 and 0.50%, 3) 0 and 0.65%, 4) 200 and 0.35%, 5) 200 and 0.50%, and 6) 200 and 0.65%. Feed intake and average daily gain did not differ among treatment groups. Plasma pH and Ca were unaffected by dietary Ca content or dietary cation-anion difference. Plasma Cl and P decreased linearly with increasing Ca content in the diet. Plasma HCO3 increased linearly with increased dietary Ca content. Plasma HCO3 and partial pressure of CO2 were higher in calves fed the 200 compared with calves fed the 0 cation-anion difference diets. Plasma Cl was, however, lower in calves fed the 200 compared with calves fed the 0 meq diets. An interaction of Ca content and dietary cation-anion difference was detected for plasma P content. Urinary pH increased linearly with increasing dietary Ca content. Calves fed the 200 meq dietary cation-anion difference had higher urinary pH values than those fed the 0 meq diet. Urinary P excretion was not altered by dietary cation-anion difference or Ca content of the diet. Calves fed the 0 meq diet had higher urinary cocnentrations of Ca and Cl when compared with those fed the 200 meq diet. Bone ash, P, Ca, Mg, and K content of the 10th rib were not affected by dietary treatments. Breaking strength of the seventh and ninth ribs increased quadratically with increasing dietary Ca content. Dietary cation-anion difference had no effect on the breaking strength of the seventh and ninth ribs. Varying the dietary cation-anion difference from 0 to 200 meq/kg of dietary dry matter had no effect on Ca requirement of the growing calf. PMID- 11210028 TI - In vitro mixed ruminal microorganism fermentation of whole cottonseed coated with gelatinized corn starch and urea. AB - We conducted an in vitro mixed ruminal microorganism fermentation study to determine the effect of coating whole cottonseed with gelatinized corn starch and feed grade urea. Treatments were arranged as a 3 x 4 factorial to provide three concentrations of starch (0.0, 2.5, and 5.0%) and four concentrations of urea (0.0, 0.25, 0.5, and 1.0%). All treatments were prepared from one lot of whole cottonseed. Batch culture fermentations were conducted using anaerobic medium that contained 20% (vol/vol) ruminal fluid in 160-ml serum bottles. Whole cottonseed was ground to pass through a 6-mm screen and weighed amounts (0, 0.4, 0.8, and 1.2 g) were added to the serum bottles. As starch increased, H2, CH4, total volatile fatty acids, and molar proportions of propionate increased linearly, whereas pH, molar proportions of acetate, and the acetate to propionate ratio decreased linearly. L-Lactate concentrations were highest with 2.5% starch compared with 0 or 5.0%. As the amount of urea in the coating increased, pH and CH4 increased linearly, whereas H2 concentrations decreased linearly. Ammonia concentrations exhibited a quadratic response due to moderate increases with the addition of 0.25 and 0.5% urea, and a greater increase was observed with 1.0% urea. Interactions between starch and urea were observed for H2, CH4, NH3, and L lactate. Concentrations of H2 decreased and CH4 was relatively constant as urea increased in the presence of 0 and 2.5% starch, but increased with 5% starch. L Lactate concentrations were unchanged (0% starch), higher (2.5% starch), or lower (5.0% starch) as urea increased. Ammonia concentrations increased after urea exceeded 10% of the starch concentration. The addition of urea did not prevent the decline in pH, but did reduce H2 and CH4 accumulation with 2.5% starch. PMID- 11210029 TI - Effects of alimet on nutrient digestibility, bacterial protein synthesis, and ruminal disappearance during continuous culture. AB - A dual effluent continuous culture system was used to investigate the effects of inclusion of Alimet (Novus International, Inc., St. Louis, MO) feed supplement [an 88% aqueous solution of dl, 2-hydroxy-4-(methylthio) butanoic acid (HMB)] in the diet on nutrient digestibility, bacterial protein synthesis and ruminal disappearance of HMB. Four fermenters were fed three times daily a basal diet that consisted of 50% grain mixture and 50% forage for 9 d. In experiment 1, four concentrations of HMB (0, 0.20, 0.77, and 1.43% DM basis) were added to the diet and fed to the fermenters twice daily. In experiment 2, two concentrations of dietary HMB (0 and 0.88% DM basis) were fed twice daily and evaluated with two solids retention times (16.7 vs. 25.0 h) and two liquid dilution rates (0.15 vs. 0.125 h(-1)). Increasing the amount of HMB in the diet did not affect nutrient digestibility, volatile fatty acid concentrations, or ruminal escape of HMB. Bacterial protein synthesis was improved with the addition of HMB during high and low retention times. The extent of HMB escaping ruminal degradation ranged from 21.6 to 43.2% and was highest at the lower retention time. It can be concluded that a fraction of HMB survives rumen microbial degradation and, therefore, provides a rumen-protected form of methionine at the same time that it improves bacterial protein synthesis. PMID- 11210030 TI - Effects of alcohol ethoxylate and pluronic detergents on the development of pasture bloat in cattle and sheep. AB - A series of studies was conducted to determine the efficacy and possible modes of action of a water-soluble mixture of alcohol ethoxylate and pluronic detergents (AEPD; Blocare 4511, ANCARE, Auckland, NZ) in preventing pasture bloat in ruminants grazing or fed freshly harvested alfalfa. Ten cannulated Suffolk wethers were offered freshly harvested alfalfa; five were given a daily intraruminal dose of 40 ml of 50% AEPD (vol/vol) 1 h before feeding, and five (controls) were dosed with water. Viscosity of ruminal fluid was reduced (P < 0.001) in AEPD-treated wethers, relative to the controls, for the first 2 h after feeding but not at 4 h after feeding and beyond. Treatment with AEPD did not affect dry matter (DM) intake, digestibility of DM, acid detergent fiber, or neutral detergent fiber, or N digestion and retention, implying that AEPD likely would not affect milk production. In a crossover grazing study, five of the wethers were given AEPD in drinking water (0.1%, vol/vol); treatment with AEPD was 100% effective for preventing bloat in sheep grazing early-bloom alfalfa for 4 h daily. Replicate grazing studies were conducted with cattle in Lethbridge, AB; Lacombe, AB; and Kamloops, BC. Treated animals received AEPD in the water (0.06%, vol/vol) and grazed vegetative alfalfa for 6 h daily. As it did with sheep, AEPD treatment effectively precluded the bloat observed in control animals. Consequently, AEPD may be a valuable tool for alfalfa pasture-based dairy production although further study is required to develop an integrated model for optimal administration under a variety of climatic conditions. PMID- 11210031 TI - Chemical composition, ensiling characteristics, and apparent digestibility of summer annual forages in a subtropical double-cropping system with annual ryegrass. AB - A 2-yr study was conducted to determine the chemical composition and digestibility of silages made from forage sorghum, pearl millet, and tropical corn managed to optimize forage quality. Silages were ensiled in upright concrete silos lined with plastic and fed to heifers to determine in vivo apparent digestibility. Samples were collected before and after ensiling to determine ensiling characteristics and forage quality. After ensiling, tropical corn had the greatest dry matter (DM), the lowest crude protein, and the greatest water soluble concentrations. Tropical corn silage had a pH of 3.96. The pH of forage sorghum silage was 4.09, and pearl millet had a pH of 4.50. Pearl millet had the lowest concentration of preensiled water-soluble carbohydrate, which likely caused the high pH in the silage. There were no differences among the forages in DM loss during ensiling in yr 2. Heifers fed pearl millet silage consumed more DM, but digestible DM intake was not different among the three groups of heifers. The results of this experiment indicate that pearl millet would be less desirable as a crop intended solely for silage production. Both forage sorghum and tropical corn could be grown specifically for ensiling based on DM digestibility. The decision on which crop to use should be based on factors such as production costs, forage yields, and local growing conditions rather than silage quality. PMID- 11210032 TI - Refinements in primary rumen epithelial cell incubation techniques. AB - The objectives of this study were to 1) determine if the number of rumen epithelial cells in primary cell incubation affects the rate of metabolite production, and 2) determine the optimum mode of data expression to standardize reporting criteria. Sections of rumen epithelial tissue were excised from five Holstein heifers and subjected to serial tryptic digestion to isolate cells. Isolated cells had a mean viability of 86% (+/- 1.29) and were incubated at concentrations of 0.5, 1, 5, 10, 20, and 40 million cells per flask. Oxidation of [1-14C]butyrate to 14CO2 and production of acetoacetate (ACAC), beta hydroxybutyrate (BHBA), lactate, and pyruvate were measured for cell dilution comparisons. Cell number, cell dry matter, cell crude protein, epithelial wet tissue weight, body weight, and metabolic body weight were measured to generate 12 different forms of data expression. Coefficients of variation were calculated for each type of expression. Expressing data per cell number resulted in the lowest variation. Oxidation of [1-14C]butyrate to 14CO2 and pyruvate production per million cells did not significantly differ between treatments for 90-min incubation. Acetoacetate and lactate concentrations were greatest at 0.5 and 1 million cells/flask, respectively, with no differences between 5 to 40 million cells/flask. Production of BHBA for 1 million cells/flask was greater than 0.5 and 40 million cells/flask, but did not change between cell concentrations 5 to 20 million. The BHBA:ACAC concentration ratios for 0.5 and 1 million cell dilutions were both 1.1 to 1 indicating low mitochondrial redox potentials. Concomitantly, lactate:pyruvate ratios for 0.5 and 1 million cells were greater than other cell dilutions, indicating a high cytosolic redox potential. The suggested range of rumen epithelial cells to include in incubations is 5 to 20 million cells/flask. This will minimize experimental error associated with using low cell numbers and the potential for reduced metabolite production caused by incubating large cell quantities. When rumen tissue taken from animals of the same species, size, and stage of development; data adjusted by cell number is preferred. However, it is recommended that cell protein, cell DM, and animal metabolic weight be included to facilitate future comparison between species and laboratories. PMID- 11210033 TI - Intestinal disappearance and mesenteric and portal appearance of amino acids in dairy cows fed ruminally protected methionine. AB - An experiment was conducted to compare the rates of disappearance of amino acids (AA) from the small intestine and their net appearance in the blood draining only the small intestine (mesenteric-drained viscera) and the whole gastrointestinal tract (portal-drained viscera) of cows fed a silage-based diet supplemented or not with ruminally protected Met. Five lactating dairy cows (118+/-4 DIM) equipped with duodenal and ileal cannulae (n = 2) or a duodenal cannula only (n = 3), two of which were multicatheterized, were fed a TMR top dressed with 0 or 72 g of ruminally protected Met per day. The addition of ruminally protected Met to the diet increased the duodenal flux of Met leading to a higher apparent digestibility of Met in the small intestine. Sixty-six percent of Met from ruminally protected Met bypassed the rumen and 82% of that Met disappeared from the small intestine. Arterial plasma Met concentrations numerically increased with ruminally protected Met (45 vs. 18 microM), while total AA concentration decreased. Feeding ruminally protected Met resulted in higher concentrations of urea-N and glucose in arterial plasma. Milk production and milk composition were unaffected. The disappearance of essential AA across the small intestine was equivalent (101%) to their flux through the mesenteric-drained viscera while the portal:mesenteric-drained viscera flux ratio for each essential AA varied from 38% for Thr to 76% for Phe. The portal:mesenteric-drained viscera flux ratio for Met was 66%. These results confirm observations made with pigs and sheep. PMID- 11210034 TI - Effects of forage neutral detergent fiber and yeast culture on performance of cows during early lactation. AB - Sixty Holstein cows were assigned to two treatments at 21 d before calving and were group-fed a prepartum diet with or without yeast culture. After parturition, cows were individually fed one of five treatments for 140 d: 1) 21% forage neutral detergent fiber (NDF) without yeast culture, 2) 21% forage NDF with yeast culture, 3) 17% forage NDF without yeast culture, 4) 17% forage NDF with yeast culture, and 5) 25% forage NDF with yeast culture for 30 d and then switched to diet 4 for 110 d. Cows fed yeast culture prepartum were also fed yeast culture postpartum (60 g/d). A quadratic increase to 25, 21, and 17% forage NDF occurred during the first 30 d in milk (DIM) for dry matter intake, milk yield, and milk protein yield. No differences were observed for yeast culture or interaction of yeast culture and forage NDF for the first 30 DIM. Feeding 17 versus 21% forage NDF increased milk protein percentage and tended to increase dry matter intake as a percentage of body weight from 31 to 140 DIM. During this period, yeast culture tended to increase milk fat percentage and appeared to have positive effects on dry matter intake, milk yield, and milk fat yield when supplemented to diets with 21% forage NDF but not with 17% forage NDF. Feeding 17% forage NDF may be too low for the first 30 DIM but may improve animal performance after 30 DIM compared to 21% forage NDF. PMID- 11210035 TI - Effects of milk fat, cocoa butter, or selected fat replacers on flavor volatiles of chocolate ice cream. AB - Selected volatile compounds of chocolate ice creams containing 0.6, 4.0, 6.0, or 9.0% milk fat or containing 2.5% milk fat, cocoa butter, or one of three fat replacers (Simplesse, Dairy Lo, or Oatrim) were analyzed by gas chromatography and gas chromatography-mass spectrometry using headspace solid-phase microextraction. The headspace concentration of most of the selected volatile compounds increased with decreasing milk fat concentration. Fat replacers generally increased the concentration of volatiles found in the headspace compared with milk fat or cocoa butter. Few differences in flavor volatiles were found between the ice cream containing milk fat and the ice cream containing cocoa butter. Among the selected volatiles, the concentration of 2,5-dimethyl-3(2 methyl propyl) pyrazine was the most highly correlated (negatively) with the concentration of milk fat, and it best discriminated among ice creams containing milk fat, cocoa butter, or one of the fat replacers. PMID- 11210036 TI - Effect of prepartum dietary protein level on performance of primigravid and multiparous Holstein dairy cows. AB - This study compared the effects of two levels of crude protein (CP) fed during late gestation on the performance, blood metabolites, and ovarian activity of Holstein cows. One-hundred and six cows (42 primigravid and 64 multiparous) 32 d before calving were divided into two groups and fed diets containing moderate (12.7% CP, 36% rumen undegradable protein, (RUP) or high (14.7% CP, 40% RUP) protein. Higher prepartum CP diet increased milk production during the first 120 d in milk (DIM), but most of that effect was detected for the primigravid cows. Primigravid cows fed the prepartum diet higher in protein produced 2.0 kg/d more milk and 3.1 kg/d more 3.5% fat-corrected milk (FCM) during early lactation. Yields of milk fat and protein in early lactation were also increased by the high prepartum CP diet fed to primigravid cows. During the complete lactation, the response to prepartum dietary protein differed between primigravid and multiparous cows. Yields of milk, 3.5% FCM, and milk fat and protein were not affected by the prepartum diet for primigravid cows, but decreased for multiparous cows fed the high protein diet. However, primigravid cows fed the high prepartum protein diet had a higher 305-d mature equivalent milk yield. Colostrum composition, blood metabolites, ovarian activity, and disease incidence were not influenced by prepartum protein. Data from this study suggest that the current prepartum protein recommendation seems to be adequate for multiparous cows, but late-gestation primigravid cows might benefit from diets with a CP content above 12.7%. PMID- 11210037 TI - Effect of dietary sulfur and selenium concentrations on selenium balance of lactating Holstein cows. AB - The effects of dietary sulfate and selenium concentrations on selenium balance in dairy cows were investigated. Midlactation Holstein cows (n = 30) were fed diets containing either 0.1 or 0.3 mg of supplemental Se (from sodium selenate)/kg of dry matter and 0, 0.2, or 0.4% added S from a mix of calcium and magnesium sulfate in a factorial arrangement. The experiment lasted 112 d. Dry matter intake was linearly reduced with increasing S, but the effect was greater when 0.3 mg/kg of Se was fed (significant interaction). Treatment effects for yields of milk, milk fat, and milk protein were similar to those for dry matter intake. Increased dietary S linearly reduced plasma Se concentrations. Increasing dietary S linearly reduced apparent (42.7, 33.1, and 30.1%) and estimated true (50.5, 46.0, and 42.3%) Se digestibility. Excretion of Se via feces (1.6 vs. 2.8 mg/d) and urine (0.5 vs. 1.3 mg/d) was higher and output in milk (0.4 vs. 0.3 mg/d) was lower for cows fed 0.3 mg/kg of Se compared with 0.1 mg/kg, but no Se effect was found for estimated true Se digestibility. Dietary S from sulfate reduced Se balance especially when cows were fed diets with less than 0.3 mg of Se/kg of diet dry matter. PMID- 11210038 TI - The effects of milk yield and stage of lactation on the partitioning of nutrients in lactating dairy cows. AB - The objective of the experiment was to examine, using indirect calorimetry, the effects of milk yield and stage of lactation on the response in milk and body tissue energy, and heat production, to a reduction (decrement) in nutrient intake (assessed as metabolizable energy intake). Eight lactating dairy cows, four representing each of two stages of lactation [either mean initial days in milk (DIM) 158 (SD 6.1) or 414 (SD 51.1)] were used. Each cow underwent four 17-d periods incorporating two physiological states [number of mammary glands milked: either four (periods 1 and 2), or two (periods 3 and 4)], and two levels of metabolizable energy intake within each physiological state [either sufficient to meet requirements for zero tissue balance plus 10 MJ/d (periods 1 and 3)] or these allowances reduced by 20 MJ/d in the subsequent period (periods 2 and 4, respectively). Partitioning was calculated from the changes in metabolizable energy intake, milk energy, tissue energy, and heat production between DIM groups and between four and two gland milking (milk yield) components of the study. Partitioning of the changes in metabolizable energy intake was not influenced by DIM, but milk yield response was greater in the early lactation cows compared with the late group. Cows milked in four glands (higher milk yield) partitioned a significantly greater proportion of decremental changes in metabolizable energy intake to milk energy and less to tissue energy, than when milked in only two glands (lower milk yield). PMID- 11210039 TI - Insulin regulates milk production and mammary gland and hind-leg amino acid fluxes and blood flow in lactating goats. AB - We investigated the roles of insulin and amino acid (AA) in regulating milk production and the uptake of AA and blood flow (BF) by the mammary gland and hind leg of goats (n = 4). During two periods, either saline or AA (65 g/d) was infused i.v. for 7.5 d, and, beginning on d 5, goats were subjected to a hyperinsulinemic-euglycemic clamp. The insulin clamp elevated plasma insulin levels threefold and insulin-like growth factor-1 by 27%, and euglycemia was maintained by the infusion of glucose. Arterial, mammary, and tarsal vein blood samples were obtained on d 4 and 8 of each period, and blood flow was monitored continuously by probes. Insulin and insulin plus AA infusions increased the yields of milk by 13 to 18% and protein by 10 to 21%, but AA infusion alone had no effect. The insulin clamp reduced milk fat content by 21 to 31% and yield by 8 to 19%, and reduced the yields of milk fatty acids >C16. The insulin clamp increased mammary blood flow by 42%, but insulin and AA infusions both increased hind-leg BF by 29 to 52% and by 25%, respectively. Net uptakes of most plasma AA by the udder were reduced by insulin, whereas AA infusion had no effect. For the leg, the uptake of His and Thr were decreased by insulin, whereas the infusion of AA stimulated the uptake of total essential AA. Insulin increased the uptake of glucose by the udder but not by the leg. This study suggests that the udder and leg tissues respond differently to infusions of insulin and AA; the udder was more responsive to insulin, while the leg was more responsive to AA concentralion (supply), at least in terms of AA uptake and net anabolism (protein gain or secretion). PMID- 11210040 TI - Evaluation of sire predicted transmitting abilities for evidence of X-chromosomal inheritance in north american sire families. AB - This study tested for differences between genetic merits of sons and daughters of sires and for evidence of segregating quantitative trait loci on the X chromosomes of North American Holsteins. Son PTA adjusted for sire PTA was used as the dependent variable to test for biases and for genes that were passed from sire to daughter but not to son. The test of variability across sires of sons merely indicated an unaccounted source of variation, for which genes on X chromosomes might be responsible. Critical values for this test and power were determined by simulation for a variety of populations and traits differing in heritability, size of the X chromosome effect, and allelic frequency. Simulated genes on the X chromosome were detected with high power at intermediate frequencies of the favorable allele. The power of the test increased as the size of the effect increased and as genetic variance attributed to autosomes decreased. The test was then applied to recently evaluated data from US and Canadian Holstein populations. Genetic evaluations for >17,000 bulls from the US and >9000 from Canada were included. Results suggested that little extra variation was present for some traits formally evaluated in North America, but that genes on the X chromosome were unlikely to be the cause. PMID- 11210041 TI - Heritabilities and correlations among body condition scores, production traits, and reproductive performance. AB - The objectives of this study were to estimate the heritability of body condition scores (BCS) from producer and consultant-recorded data and to describe the genetic and phenotypic relationships among BCS, production traits, and reproductive performance. Body condition scores were available at calving, postpartum, first service, pregnancy check, before dry off, and at dry off from the Dairy Records Management Systems in Raleigh, NC, through the PCDART program. Heritabilities, genetic correlations, and phenotypic correlations were estimated assuming an animal model using average information REML. Herd-year-season effects and age at calving were included in all models. Prior calving interval was included in models for second and third lactations. Analyses that included reproductive traits were conducted with and without mature equivalent milk as a covariable. Heritability estimates for BCS ranged from 0.09 at dry-off to 0.15 at postpartum in first lactation. Heritability estimates ranged from 0.07 before dry off to 0.20 at pregnancy check in second lactation and from 0.08 before dry-off to 0.19 at first service in third lactation. Genetic correlations between adjacent BCS within first lactation were greater than 0.96 with the exception of calving and postpartum (0.74). In second lactation, adjacent genetic correlations were 1.0 with the exception of calving and postpartum (0.84). Genetic correlations across lactations were greater than 0.77. Phenotypic correlations between scoring periods were highest for adjacent scoring periods and when BCS was lowest. Phenotypic correlations were lower than genetic correlations, i.e., less than 0.70. Higher BCS during the lactation were negatively related to production, both genetically and phenotypically, but the relationship was moderate. Higher BCS were favorably related genetically to reproductive performance during the lactation. PMID- 11210042 TI - Parallel computing applied to breeding value estimation in dairy cattle. AB - Continuous genetic evaluation of dairy cattle with test-day models is desired in Finland. However, the computing time for the genetic evaluation is 4 d and exceeds the minimum of a weekend. Three parallel implementations of the preconditioned conjugate gradient iterative solver were programmed and compared to identify the best strategy for solving mixed model equations using parallel computing. The programs were used to solve two random regression test-day models with approximately 7.28 and 49.9 million unknowns. The latter model will be used in the Finnish dairy cattle evaluation. Computing times for the smaller model with the four processors available were 52, 32, and 27% of the single processor program when the complexity of the parallel program was increased. In practice, the best program required the most programming because the other parallel programs could not solve the larger model because of excess memory requirements. Parallel computing with four processors reduced the time to obtain solutions of Finnish dairy cattle evaluations to under 2 d. Benefit from parallel computing will be increased if amount of computing memory is increased. PMID- 11210043 TI - Genetic parameters for cystic ovarian disease in dutch black and white dairy cattle. AB - Cystic ovarian disease (COD) is one of the most frequently diagnosed gynecological findings in dairy cattle. It causes temporary infertility and is likely to affect reproduction as well as production parameters in cows. The objectives of this study were to investigate the heritability of COD in a Dutch Black and White population and to estimate the genetic and phenotypic relationships with milk production traits. In the data set used, the overall incidence of COD was 7.7% (1204 COD diagnoses in 15,562 lactations). The farm incidence varied between 1.9 and 11.3%. The estimated heritabilities on the underlying and observable scales were 0.102 and 0.087, respectively. The genetic correlations between COD and 305-d milk, fat, and protein yields were 0.345, 0.379, and 0.441, respectively. We concluded that a genetic predisposition for COD exists in Dutch Black and White dairy cattle. The genetic correlations between COD and yield traits indicate that ongoing selection for production will increase the incidence of COD. PMID- 11210044 TI - Identification and characterization of elevated microbial counts in bulk tank raw milk. AB - The bacterial composition of bulk tank milk from 13 farms was examined over a 2 wk period to characterize sudden elevations in the total bacterial count referred to as "spikes." Bulk tank milk samples collected at each pick-up were analyzed for standard plate count, Petrifilm aerobic count, somatic cell count, gram negative organisms, and streptococci. Twenty standard plate count spikes were observed: 12 associated with streptococci, 4 associated with gram-negative organisms, 2 associated with streptococci and gram-negative organisms, and 2 that were not definitively characterized. Spikes ranged from 14,000 to 600,000 cfu/ml. Streptococcus uberis was isolated as the predominant organism from 11 spikes, and Escherichia coli was isolated from 4 spikes. Statistical analysis of total bacterial counts indicated a high correlation (r = 0.94) between standard plate counts and Petrifilm aerobic count. Regression analysis of standard plate counts and Petrifilm aerobic counts yielded the equation log10 (standard plate count) = 0.73 + 0.85log10 (Petrifilm aerobic count), indicating that the correlation, although strong, is not one to one. In a related pilot study, triplicate bulk tank milk samples were collected and analyzed for total bacterial count and presumptive streptococcus, gram-negative, and staphylococcus counts. Two-way ANOVA of these triplicate data indicated a lack of significant variation among the triplicate samples, suggesting that one sample can reliably gauge the microbial status of the entire bulk tank. PMID- 11210045 TI - Deep-stacked broiler litter as a protein supplement for dairy replacement heifers. AB - Fifty Holstein dairy heifers, [two replications of 25 heifers; average body weight (BW) 227 kg], were assigned to one of the following treatments for 105 d. Treatments 1 through 4 are given as the percentage of supplemental crude protein (CP) from soybean meal and deep-stacked broiler litter, respectively: 1) 100 and 0%; 2) 67 and 33%; 3) 33 and 67%; 4) 0 and 100%; and 5) 67% of supplementary CP from deep-stacked broiler litter and 33% from a source of rumen undegradable protein (RUP). All rations were formulated to contain 15% CP and 68% TDN on a dry matter basis. Dry matter intake was not significantly different among treatments at 10.1, 10.2, 10.4, 9.4, and 9.1 kg/d for treatments 1 through 5, respectively. Average daily BW gains (1.35, 1.37, 1.28, 1.17, and 1.24 kg/d for treatments 1 through 5, respectively) decreased linearly as the level of litter feeding increased and was not influenced by increasing RUP in treatment 5. Feed efficiency was not affected by the level of deep-stacked broiler litter feeding. Ruminal ammonia and plasma urea nitrogen concentrations decreased linearly as the level of litter feeding increased. Feeding additional RUP decreased ruminal ammonia concentration in treatment 5 to a level similar to treatment 4. This suggests that the protein in deep-stacked broiler litter may be more undegradable than that in soybean meal and that RUP in broiler litter may be higher than previously thought. Results from this study indicate that deep-stacked broiler litter has potential as a low-cost CP source for growing dairy heifers. PMID- 11210046 TI - Effect of the fat globule sizes on the meltdown of ice cream. AB - The meltdown of ice cream is influenced by its composition and additives and by fat globule size. The objective of this study was to examine the effect of fat globule size and fat agglomerate size on the meltdown stability of ice cream. Therefore, an ice cream mix (10% milk fat) was homogenized at pressures ranging from 0 to 30 MPa in single-stage, double-stage, and selective homogenization processes. The ice cream, produced on a continuous ice cream freezer, was characterized by an optimized meltdown test while, in addition, the fat globule sizes and the free fat content were determined in the mix and the molten ice cream. The meltdown was dependent on the fat agglomerate sizes in the unfrozen serum phase. Agglomerates smaller than a critical diameter led to significantly higher meltdown rates. Homogenization pressures of at least 10 MPa were sufficient to produce a stable ice cream. Furthermore, proof was provided that double-stage homogenization is not necessary for fat contents up to 10% and that selective homogenization is possible to produce stable ice creams. Based on these results a model was deduced describing the stabilizing mechanisms during the meltdown process. PMID- 11210047 TI - On reflectometric measurement of a refractive index of milk. AB - The refractive index of milk samples was measured with a reflectometer. Fresnel's formula for intensity reflectance and the concept of critical angle were applied to measured data. Milk samples were also measured with surface plasmon resonance sensor for refractive index assessment. The experiments were carried with commercial milk that had fat volume concentrations of 0.004, 1.53, and 3.55%. We observed that simultaneously quantitative information about the refractive index and absorption of milk, as a function of fat concentration, could be obtained with both devices. PMID- 11210048 TI - Cation-exchange purification of mutagenized bovine beta-casein expressed in transgenic mouse milk: its putative Asn68-linked glycan is heterogeneous. AB - Bovine beta-casein (A2 genetic variant) was mutagenized to (L70S/P71S) and expressed in transgenic mouse milk. This protein now carries the signal (N68S69S70S71) that mimics a consensus eukaryotic glycosylation signal (N-X-S/T) (3). Hypothetically this protein should be glycosylated at N68 by any eukaryotic organism producing it. This novel protein was purified from transgenic mouse milk by Mono-S cation-exchange fast protein liquid chromatography (FPLC). The novel beta-casein was separated without cross contamination from mouse caseins by using acetate buffer (pH 5.0) in the presence of 6 M urea, octyl-glucopyranoside and 2 beta-mercaptoethanol. The purified (L70S/P71S) beta-casein showed an N-linked oligosaccharide attached to Asn68 and different lectin binding profiles compared with the same protein expressed in yeast. The mouse-expressed beta-casein (L70S/P71S) was specific to Concanavalin A, wheat germ agglutinin, Erythrina cristagalli agglutinin, and Ulex europaeus, indicating its oligosaccharide structure is different in the mammary gland of mouse than the reported glycosylated beta-casein expressed in Pichia pastoris (4). In addition, the five serine residues located at amino terminus of wild type bovine beta-casein were shown to be normally phosphorylated as in native bovine beta-casein. PMID- 11210050 TI - Proteolysis of beta-casein as a marker of Grana Padano cheese ripening. AB - Proteolysis has a critical role in defining the typical organoleptic characteristics of Grana Padano, a well-known Italian cheese. During the ripening process, hydrolysis of beta-casein produces different fragments, the most abundant and widely studied of which are gamma-caseins, three polypeptides containing the HOOC-terminal portion of beta-casein. By sodium dodecyl sulfate PAGE and a specific anti-beta-casein monoclonal antibody, two beta-casein-derived bands were identified in Grana Padano cheese: betaa and betab. Thanks to the identification of the amino acid sequences, it was shown that: a) betaa contains gamma1-casein [beta-casein (29-209)] and the correlated peptide [beta-casein (30 209)]; b) betab contains gamma2-casein [beta-casein (106-209)] and gamma3-casein [beta-casein (108-209)]. The production of betaa and betab by the three enzymes most involved in cheese proteolysis (pepsin, chymosin, and plasmin) was evaluated by performing in vitro digestions. A significant correlation between abundance of some polypeptides and ripening process was shown. PMID- 11210049 TI - Isolation, characterization, and influence of native, nonstarter lactic acid bacteria on Cheddar cheese quality. AB - To determine whether adventitious nonstarter lactic acid bacteria (NSLAB) might affect cheese flavor and quality, we studied a population of NSLAB present in 30 premium quality Cheddar cheeses (3-mo ripened) produced at a commercial facility in the United States. DNA fingerprinting analysis with a sensitive strategy for arbitrary priming polymerase chain reaction showed that 75 isolates corresponded to at least 18 distinct nonstarter organisms. According to ribotype database comparisons of representatives from the 18 groups, 9 matched Lactobacillus (closest to paracasei species), 8 matched Streptococcus thermophilus, and 1 matched to a Lactococcus species. This finding indicated that among the 75 NSLAB isolates, Lactobacillus made up 64%, S. thermophilus 32%, and Lactococcus 4%. Isolates representing 11 NSLAB groups were characterized for protease, peptidase, and diacetyl production. Based on this phenotypic analysis, two Lactobacillus isolates were evaluated as adjuncts in Cheddar cheese. All of the NSLAB identified from the adjunct cheese at 3 mo by DNA fingerprinting consisted of the adjunct lactobacilli, showing that the adjunct strains predominated throughout the early stages of ripening. The impact of adjunct lactobacilli was evident after 6 mo when free amino acids significantly increased and sensory scores improved in adjunct cheese as compared with a control cheese. The largest impact was found in adjunct cheese containing a blend of both lactobacilli strains. These results show that certain adventitious NSLAB positively contribute to flavor development. PMID- 11210051 TI - A survey of lipolytic and glycolytic end-products in commercial Cheddar enzyme modified cheese. AB - The concentrations of L- and D-lactic acid and free fatty acids, C4:0 to C18:3, were quantified in a range of commercial enzyme-modified Cheddar cheeses. Lactic acid in Cheddar enzyme-modified cheeses varied markedly depending on the manufacturer. Differences in the ratio of L- to D-lactic acid indicate that cheeses of different age were used in their manufacture or contained varying levels of nonstarter lactic acid bacteria. The level of lipolysis in enzyme modified cheese was higher than in natural Cheddar cheese; butyrate was the predominant free fatty acid. The addition of exogenous acetate, lactate, and butyrate was also indicated in some enzyme-modified cheeses and may be used to confer a specific flavor characteristic or reduce the pH of the product. Propionate was also found in some enzyme-modified cheese products and most likely originated from Swiss-type cheese used in their manufacture. Propionate is not normally associated with natural Cheddar cheese flavor; however, it may be important in the flavor and aroma of Cheddar enzyme-modified cheese. Levels of lipolysis and glycolysis appear to highly controlled as interbatch variability was generally low. Overall, the production of enzyme-modified Cheddar cheese involves manipulation of the end-products of glycolysis (lactate, propionate, and acetate) and lipolysis to generate products for specific applications. PMID- 11210052 TI - Optimization of the PCR for detection of Staphylococcus aureus nuc gene in bovine milk. AB - Staphylococcus aureus is an economically important and a major mastitis-causing pathogen that also poses food safety and antimicrobial resistance threats. Substances in mastitic milk inhibit the Taq DNA polymerase reaction (Taq PCR) making it of limited use for detecting S. aureus mastitis. In the study reported here, a set of oligonucleotide primers of 21 and 24 bases was used in Taq-PCR to amplify DNA from S. aureus (isolates from bovine mastitis). A specific amplicon of 270 bp was generated as predicted. Replacing Taq DNA polymerase with Thermus thermophilus (Tth) DNA polymerase alone (Tth-PCR) raised the sensitivity of S. aureus detection in milk from experimentally infected cows from 65 to 80%. Combining the use of Tth DNA polymerase and the purification of crude DNA extract using Chelex-100 before PCR raised the sensitivity to 100%. In a random survey involving 100 milk samples from cattle not infected with S. aureus, the test was 100% specific. With milk samples from clinical cases of bovine mastitis, 100% sensitivity and specificity were also observed. It is concluded that Tth-PCR on milk samples with the purification of crude DNA extracts using Chelex-100 is as sensitive as but faster than conventional milk bacteriological culture techniques and is highly specific. The modified PCR correlates with elevated somatic cell counts, detects evidence of chronic and resolving infection based on S. aureus specific DNA and circumvents the endogenous inhibitory effects of milk. PMID- 11210053 TI - Tail docking dairy cattle: effects on cow cleanliness and udder health. AB - To determine whether tail docking would influence cow cleanliness and udder health in a free-stall system, we monitored milking cows after half the animals in a herd were docked. A sample of 223 docked and 190 undocked cows (reducing to 169 and 105 over the study as cows were dried off) were monitored for 8 wk. Cow cleanliness was scored in two areas: along the spine, and the rump adjacent to the tail at 1, 2, 3, 5, and 8 wk after docking. Cleanliness was evaluated by counting squares that were soiled (0 to 14 on a 5- x 17.5-cm grid) and judging soiling severity on a scale from 0 (clean) to 3 (thickly caked). Udder cleanliness was scored with the same scale (0 to 3) and by counting the number of teats with debris on them. Udder health was assessed by measuring SCC of two milk samples and the number of animals diagnosed as mastitic by the on-farm veterinarian. No treatment differences were found in four measures of cow cleanliness, two measures of udder cleanliness, or udder health. However, cow cleanliness did differ over time, and analysis of a subsample of cows illustrated individual differences in cleanliness. PMID- 11210054 TI - Effects of the persistent dominant follicle on the ability of follicle stimulating hormone to induce follicle development and ovulatory responses. AB - Three experiments were conducted to evaluate the effect of an induced first wave persistent dominant follicle on folliculogenesis and ovulatory responses induced by FSH. On d 6 of a synchronized estrous cycle (d 0 = estrus), cows were treated with a Syncromate-B implant and two injections of PGF2, (25 mg, 0700 h; 15 mg, 1900 h, i.m.). Cows in the control group retained a first-wave persistent dominant follicle, but in the aspirated group, the first-wave dominant follicle was removed via transvaginal aspiration on d 10 (d 0 = estrus). Beginning on d 12, cows received 32 mg of FSH-P i.m. in decreasing doses at 12-h intervals over a 4-d period. On d 15, the Syncromate-B implant was removed, and cows were ovariectomized (experiment 1, n = 8) or inseminated (experiment 2, n = 11) at 10 and 22 h after the onset of estrus. Cows in experiment 3 received a used controlled intravaginal drug releasing (CIDR) device and two injections of PGF2alpha (25 mg, 0700 h; 15 mg, 1900 h; i.m.) on d 6. On d 8, the first-wave dominant follicle was aspirated (n = 6) or left intact (n = 5), and FSH treatment was initiated (20 mg of Folltropin in decreasing doses at 12-h intervals over a 4 d period), and on d 10 the used CIDR device was removed from all cows. Ovarian follicle size and number were examined daily by ultrasonography from d 5 of the estrous cycle. The persistent dominant follicle increased in size from 10.7 mm on d 5 to 15.4 mm on d 10 (experiments 1 and 2), and from 9 mm on d 5 to 20.4 mm on d 11 (experiment 3). From d 11 to 14, the number of class 1 (2 to 5 mm) follicles was lower in the aspirated group than in the control group; the number of class 2 (6 to 9 mm) follicles was higher on d 12 and 13 for the aspirated group (experiments 1 and 2). The number of class 3 (> or =10 mm) follicles was higher in the aspirated group on d 14 to 16, but the same on d 17. Ovarian and embryo responses to superovulation did not differ between groups. In experiment 3, the numbers of class 1, 2, and 3 follicles, as well as ovarian and embryo responses following ovulation did not differ between groups. Initiation of exogenous FSH treatment appears to override any systemic inhibitory effect that a persistent dominant follicle may be exerting at the pituitary and possibly the ovary. PMID- 11210055 TI - A cross-cultural study of suicide intent in parasuicide patients. AB - As part of the WHO/EURO Multicentre Study on Parasuicide, the level of suicide intent among female and male parasuicide patients from various European regions was compared. From nine regions, a total of 1,212 parasuicide patients, 752 females and 460 males, were included in the study. Although some statistical significant differences in level of suicide intent between the regions and genders were found, the effect sizes of these relationships were so small that the differences have neither theoretical nor practical significance. As far as level of suicide intent is concerned, the WHO study has succeeded in recruiting a relatively homogeneous group of self-harming patients across borders of region, culture, and country. PMID- 11210056 TI - Trends in suicide ideation and suicidal behavior among high school students in the United States, 1991-1997. AB - To examine trends in suicide ideation and behavior over time, the authors analyze data from nationally representative samples of between 10,904 and 16,296 students participating in the 1991, 1993, 1995, and 1997 Youth Risk Behavior Surveys. These data describe the proportion of United States students in grades 9 through 12 that reported having (1) seriously considered attempting suicide, (2) made a plan to attempt suicide, (3) attempted suicide, and (4) made an injurious suicide attempt. From 1991 to 1997, the percentage of students seriously considering suicide and the percentage that made a suicide plan showed significant linear decreases. However, the percentage of students that made an injurious suicide attempt showed a significant linear increase. These trends make it unlikely that relevant national health objectives for the year 2000 will be met. Additional efforts are needed to identify and disseminate strategies that effectively reduce suicidal thoughts and behaviors among adolescents. PMID- 11210057 TI - Use of paracetamol (acetaminophen) for suicide and nonfatal poisoning: worldwide patterns of use and misuse. AB - Paracetamol (acetaminophen) is one of the most frequently used drugs in intentional overdoses. We have investigated associations between its availability and its use for overdose and suicide around the world by means of a postal questionnaire and literature review. Countries that limit the quantity of paracetamol available in a single purchase generally report lower rates of paracetamol-related morbidity and mortality. National policy decisions regarding restrictions on its availability need to weigh the inconvenience caused to the many who use the drug safely against those of the few in whom overdose may be fatal. We recommend restricting the quantity of drug available as a single purchase as the most pragmatic means of reducing paracetamol-related suicide and liver failure. PMID- 11210058 TI - Risk of future suicide attempts in adolescent psychiatric inpatients at 18-month follow-up. AB - This study investigated potential predictors of suicidal behavior in adolescents during an 18-month follow-up period. Subjects included 60 adolescent psychiatric inpatients initially assessed in a private psychiatric hospital. Follow-up suicidality was most strongly predicted by high intake levels of hopelessness, and an increase in or persistent problems with depression during follow-up. Some family functioning variables measured at intake were predictive of suicidal behavior at the univariate level but did not add to the predictive ability of individual functioning variables. A mediational model was proposed in which the impact of family functioning on adolescent suicidality is mediated by its impact on individual functioning. PMID- 11210060 TI - Domestic violence, separation, and suicide in young men with early onset alcoholism: reanalyses of Murphy's data. AB - Partner violence and partner separation at the time of completed suicide were investigated in 42 male alcoholics originally described by Murphy (1992). Half of the men had domestic violence histories. Partner-violent men were younger, had an earlier age of onset of alcoholism, and were more likely to be separated from their partner at the time of death than partner-nonviolent men. Loss of a close personal relationship, often a domestic partner, is common during the last year of life among alcoholic men completing suicide. Domestic violence appears to typify many of their domestic relationships, particularly among younger men and men with early onset alcoholism. PMID- 11210059 TI - Cultural orientation, family cohesion, and family support in suicide ideation and depression among African American college students. AB - This study extends previous research by examining the role of communalism, family cohesion, and family support in suicide ideation and depression in African American college students. Participants were 188 African American introductory psychology students (126 female, 61 male) from a historically black college. (1) Results showed that communalism, family cohesion, and family support were positively associated with each other. Higher levels of family cohesion and family support were associated with lower levels of suicide ideation and depression. Linear regression analyses showed a main effect for communalism and family support. Having strong communal values was positively related to suicide ideation and depression. Having strong family support was associated with fewer experiences of suicide ideation and depression. Stepwise regression analyses indicated that family support explained more variance in suicide ideation and depression than family cohesion. Implications of these results for future research and practice are discussed. PMID- 11210061 TI - Prison suicides in Austria, 1975-1997. AB - Suicide prevention in custody is hampered by the lack of funds and professional staff. In order to evaluate the prison suicide phenomenon, a study was conducted evaluating all suicides that occurred in Austrian prisons between 1975 and 1997 (n = 220). In addition to evaluating the number of male versus female suicides, the preferred suicide methods were studied, as well as suicide risk of different circumstances of custody. Suicide rates of distinguishable, important subgroups of prisoners were calculated. The suicide rate for prisoners on remand was 236.0 per 100,000, and for offenders classified as mentally ill it was 205.4 per 100,000. That is about 8 times higher than the suicide rate in Austria's general population (1975-1997: 24.6 per 100,000). The suicide rate for sentenced offenders was 81.3 per 100,000, about twice the suicide rate in Austria's general male population. We recommend that psychologists or psychiatrists concentrate on the suicide prevention of high-risk offenders after screening the newly admitted offenders for their propensity to suicide. PMID- 11210062 TI - Correctional suicide prevention in the year 2000 and beyond. AB - Although the problem of suicide in jail and prison historically has been ignored, significant insight has been gained over the past several decades due primarily to increasing litigation. This article provides a brief overview of the progress in research, programming, and policy. The new millennium offers exciting opportunities for continued growth in correctional suicide prevention. The key areas of process research, risk assessment, and public and penological policy changes are reviewed and considered vital for the field's advancement. PMID- 11210063 TI - The multi-attitude suicide tendency scale: further validation with adolescent psychiatric inpatients. AB - The present study was designed to examine the construct validity and psychometric properties of the Multi-Attitude Suicide Tendency Scale in adolescent psychiatric inpatients. This new scale has four subscales: attraction to life, repulsion by life, attraction to death, and repulsion by death. Confirmatory factor analysis of the scale items provided support for the fit of the 28-item, four-factor model. Results of logistic regression analyses revealed that high scores on the repulsion by life and the attraction to death subscales were useful in assessing the risk for suicide attempts. Results of the hierarchical regression analysis showed that high repulsion by life and low attraction to life subscale scores contributed to the prediction of scores on the suicide probability scale. We also examined gender differences on the four subscales and the psychological correlates of each subscale. PMID- 11210064 TI - Primo Levi's death: physicians and the ruling of suicide. PMID- 11210065 TI - Persistent presence of Bacteroides forsythus as a risk factor for attachment loss in a population with low prevalence and severity of adult periodontitis. AB - BACKGROUND: Previous longitudinal studies investigating the role of microorganisms in periodontitis have focused on subjects with a high prevalence and severity of disease. The complex profile of microbial species in severe cases of periodontitis might not allow us to differentiate which bacterial species initiate disease or which species simply proliferate after disease progression. This prospective longitudinal study followed a group of 205 subjects who showed a low prevalence and severity of adult periodontitis, and thus allowed us to monitor early microbiological changes in the development of periodontitis. METHODS: Subgingival plaque was collected from proximal surfaces of a posterior sextant at 6-month intervals for 2 years. During the monitoring period, 44 subjects had either attachment loss or attachment gain. Using multiplex polymerase chain reaction (PCR), all plaque samples from those 44 subjects were analyzed for the presence of Actinobacillus actinomycetemcomitans, Bacteroides forsythus, and Porphyromonas gingivalis. RESULTS: Both subjects with attachment loss and those with attachment gain had a high prevalence of these 3 periodontal pathogens. The mere presence of any of the 3 species at a site could not predict future attachment loss at that specific site. However, subjects with a persistent presence of B. forsythus at any site across all visits had 5.3 times higher odds of having at least one site in their mouth losing attachment compared to subjects with occasional or no presence of B. forsythus. CONCLUSIONS: The persistence of B. forsythus identified subjects at higher risk, but not which specific sites in those subjects would lose attachment. PMID- 11210066 TI - Gingival overgrowth as the initial paraneoplastic manifestation of Hodgkin's lymphoma in a child. A case report. AB - BACKGROUND: The purpose of this paper is to present the first case of gingival overgrowth, premature root resorption, and alveolar bone loss, which preceded the diagnosis of a stage IVB Hodgkin's lymphoma (HL) in a 9-year-old boy. METHODS: The child presented complaining of gingival pain which first appeared 3 months prior. Clinical examination revealed inflamed, hyperplastic gingivae, while x-ray showed premature root resorption and alveolar bone loss. Medical work-up was significant for cervical lymphadenopathy. Gingival biopsy, followed by lymph node resection, was performed twice. RESULTS: Histological examination of both gingival biopsies disclosed a mixed inflammatory infiltrate, while classical Hodgkin's lymphoma of the nodular sclerosis type was diagnosed from the second lymph node biopsy. Chemotherapy was instituted with mustard-vincristine procarbazine-prednizone and adriamycine-bleomycine-vinblastine-dacarbazine. Remission of the lymphoma was observed with concomitant regression of the gingival overgrowth. CONCLUSIONS: The inflammatory gingival overgrowth, premature root resorption of deciduous teeth, and alveolar bone loss in this case, in conjunction with the regression of gingival overgrowth which followed the completion of chemotherapy, are strongly indicative of a paraneoplastic manifestation of HL. The postulated mechanism for the development of the manifestation is the constitutive activation of the transcription factor NF-kB. The gingival inflammatory reaction was probably further aggravated by the bacterial-stimulated cytokine secretion released by monocytes. PMID- 11210067 TI - Detection of hepatitis C virus RNA from gingival crevicular fluid and its relation to virus presence in saliva. AB - BACKGROUND: To search for a possible source of hepatitis C virus (HCV) in saliva, the presence and shedding patterns of HCV in gingival crevicular fluid (GCF) and saliva of HCV viremic patients were assessed based on clinical, biochemical, histological, virological, and oral health parameters. METHODS: Saliva and GCF samples of 50 HCV viremic patients were collected to detect HCV RNA by a modified commercial polymerase chain reaction (PCR) assay. Clinical oral examination was performed and periodontal status at the collection sites was monitored. The results were correlated to specified parameters. RESULTS: HCV RNA was detected in 59% (29/49) of the GCF specimens and in 35% (17/48) of the saliva specimens. In saliva specimens, HCV RNA was detected only in cases which also had detectable HCV RNA in the GCF samples (P=0.00002) and was significantly related to the presence of blood in saliva (P=0.03). Higher, but not significant, values of oral clinical parameters at the sites of fluid collection were found in GCF specimens harboring HCV RNA. In GCF specimens with no blood detected, HCV RNA was more often present in cases with higher plasma viral load (P=0.05). CONCLUSIONS: The results suggest that besides blood, the other most probable source of HCV in saliva is GCF. Unknown endogenous HCV inhibitory mechanisms in the oral cavity may explain the discrepancies in HCV appearance between saliva and GCF. The results provide a biologic basis for further investigation of the role of HCV in the pathogenesis of periodontal disease. PMID- 11210068 TI - Will implants survive well in patients with a history of inflammatory periodontal disease? PMID- 11210069 TI - Relationship between crevicular aspartate aminotransferase levels and periodontal disease progression. AB - BACKGROUND: Aspartate aminotransferase (AST), an enzyme released from necrotic cells, has been identified in gingival crevicular fluid (GCF), and elevated levels are associated with periodontal tissue destruction. The aim of this study was to examine the relationship between elevated GCF levels of AST and periodontal disease progression. METHODS: Over a 12-month period, 8 to 10 interproximal sites in 41 periodontitis subjects (PS) and 15 healthy subjects (HS) were monitored. Clinical measurements included relative attachment level (RAL), probing depth, and bleeding on probing (BOP). Semiquantitative levels of GCF AST (< 800 microIU, > or = 800 microIU, and > or = 1,200 microIU) were determined using a chairside assay. At the 6- and 12-month visits, scaling and root planing and prophylaxis were performed in the PS and HS, respectively. Sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) were calculated for 2 diagnostic criteria (AST > or = 800 microIU, AST > or = 1,200 microIU) utilizing 4 thresholds of disease progression as determined by 2 methods (absolute change in relative attachment level and cumulative sum [CUSUM]). RESULTS: The percentage of sites exhibiting AST > or = 800 microIU, AST > or = 1,200 microIU, and BOP in the PS was significantly (P<0.02) lower at 6 and 12 months compared to baseline. The use of crevicular AST activity to monitor periodontal disease progression was associated with many false-positive results. Overall, low specificities, PPV, and odds ratios were demonstrated by the assay when using 2 diagnostic criteria and 4 thresholds of disease progression. The high NPV suggest that a negative AST test result was indicative of a periodontally stable site. CONCLUSIONS: These results demonstrate that elevated levels of AST were present at sites that did not subsequently exhibit disease progression. The high prevalence of AST-positive sites due to gingival inflammation diminished the test's ability to discriminate between progressive and stable, but inflamed, sites. PMID- 11210070 TI - A comparative study utilizing open flap debridement with and without enamel matrix derivative in the treatment of periodontal intrabony defects: a 12-month re-entry study. AB - BACKGROUND: Previous studies have demonstrated that enamel matrix derivative (EMD) has the ability to improve clinical parameters when used to treat intraosseous defects. The purpose of the present study was to compare at 12 months postsurgery sites treated with open flap debridement (OFD) alone to those treated with OFD and EMD. METHODS: Twenty-three subjects with at least 2 intrabony defects were chosen. Fifty-three defects received EMD in conjunction with OFD. Thirty-one defects in these same 23 subjects were treated with OFD alone. Stents were fabricated to serve as fixed reference points. Re-entries were performed at least 1 year after initial surgery. Soft tissue measurements were recorded prior to initial surgery and prior to re-entry for gingival (GI) and plaque (PI) indices, probing depth (PD), gingival margin position, and clinical attachment level (CAL). Hard tissue measurements were recorded during the initial and re-entry surgery for level of crestal bone and depth of defect. Statistical analysis was conducted using the method of generalized estimating equations to determine changes in GI, PI, PD, CAL, fill of the osseous defect, and crestal resorption. Percent of defect fill was also calculated. RESULTS: In all categories, treatment with EMD (test) was superior to treatment without EMD (control). Average PI and GI were not significantly different either initially or prior to re-entry. The average PD reduction was 2.7 mm greater with EMD than controls. The average CAL gains were 1.5 mm greater, and the average fill of osseous defect 2.4 mm greater with EMD than controls. The average percent of defect fill after adjusting for crestal bone loss was more than 3 times greater for EMD versus control-treated sites (74% defect fill with EMD versus 23% defect fill for control sites). CONCLUSIONS: This study indicates that treatment of periodontal intraosseous defects with EMD is clinically superior to treatment without EMD (open flap debridement) in every parameter evaluated. Re-entry data demonstrate that percent fill of osseous defects treated with EMD compares favorably with the treatment results utilizing bone grafts or membrane barriers, according to published literature. PMID- 11210071 TI - Long-term results of guided tissue regeneration therapy with non-resorbable and bioabsorbable barriers. I. Class II furcations. AB - BACKGROUND: The aim of this 5-year follow-up study was to clinically and radiographically evaluate the long-term results after guided tissue regeneration (GTR) therapy of Class II furcation defects using non-resorbable and bioabsorbable barriers. METHODS: Nine pairs of contralateral Class II furcation defects were treated in 9 patients with advanced periodontitis. Within each patient, one defect received a non-resorbable (expanded polytetrafluoroethylene [ePTFE]; control, C) barrier and the other a bioabsorbable (polyglactin 910; test, T) barrier by random assignment. At baseline, 6, and 60 +/- 3 months after surgery, clinical parameters and standardized radiographs were obtained. Gain of bone density within furcation areas was assessed using subtraction radiography. RESULTS: Six and 60 months after GTR therapy, statistically significant (P <0.05) horizontal attachment (CAL-H) gain was observed in both groups (C6: 1.7 +/- 0.8 mm; C60: 1.6 +/- 1.2 mm; T6: 2.0 +/- 0.7 mm; T60: 2.2 +/- 0.9 mm). However, 1 furcation assessed as Class I six months after GTR therapy with a bioabsorbable barrier had progressed to Class III after 5 years, and in another patient, 5 years after placement of an ePTFE barrier, 1 furcation had lost all the CAL-H gain that had been observed at 6 months. Subtraction analysis revealed similar area gain in both groups 6 and 60 months postsurgically (C6: 0.3 +/- 0.5; C60 1.0 +/- 1.7; T6: 0.4 +/- 0.4; T60: 1.1 +/- 1.7). CONCLUSIONS: CAL-H gain achieved after GTR therapy in Class II furcations was stable after 5 years in 16 of 18 defects. The study failed to show a statistically significant difference in stability of CAL-H gain between control and test groups 5 years after GTR therapy. PMID- 11210072 TI - Cigarette smoking negatively affects healing response following flap debridement surgery. AB - BACKGROUND: The purpose of the present parallel design, controlled clinical trial was to evaluate the treatment outcome following flap debridement surgery (FDS) in cigarette smokers compared to non-smokers. METHODS: After initial therapy, 57 systemically healthy subjects with moderate to advanced periodontitis who presented with one area (at least 3 teeth) where surgery was required were selected. Twenty-eight patients (mean age: 39.6 years, 20 males) were smokers (> or = 10 cigarettes/day); 29 patients (mean age: 43.9 years, 7 males) were non smokers. Full-mouth plaque (FMP) and bleeding on probing (BOP) scores, probing depth (PD), clinical attachment level (CAL), and recession depth (RD) were assessed immediately before and 6 months following surgery. Only sites with presurgery PD > or = 4 mm were used for statistical analysis. RESULTS: Presurgery FMP and BOP were similar in smokers and non-smokers and significantly decreased postsurgery in both groups. Overall, PD reduction and CAL gain were greater, although not significantly, in non-smokers (2.4 +/- 0.9 mm and 1.6 +/- 0.7 mm, respectively) than in smokers (1.9 +/- 0.7 mm and 1.2 +/- 0.7 mm, respectively). For moderate sites (PD 4 to 6 mm), no significant differences in PD and CAL changes were found between groups. For deep sites (PD > or = 7 mm), PD reduction was 3.0 +/- 1.0 mm in smokers and 4.0 +/- 0.8 mm in non-smokers, and CAL gain amounted to 1.8 +/- 1.1 mm in smokers and 2.8 +/- 1.0 mm in non-smokers (P = 0.0477). In smokers, 16% of deep sites healed to postsurgery PD values < or = 3 mm as compared to 47% in non-smokers (P = 0.0000); 58% of deep sites in smokers showed a CAL gain > or = 2 mm, as compared to 82% in non-smokers (P = 0.0000). CONCLUSIONS: Results of the study indicated that: 1) FDS determined a statistically significant PD reduction and CAL gain in patients with moderate to advanced periodontitis; 2) smokers exhibited a trend towards less favorable healing response following FDS compared to non-smokers, both in terms of PD reduction and CAL gain; and 3) this trend reached clinical and statistical significance at sites with initial deep PD. PMID- 11210073 TI - Potential associations between chronic respiratory disease and periodontal disease: analysis of National Health and Nutrition Examination Survey III. AB - BACKGROUND: Associations between poor oral health and chronic lung disease have recently been reported. The present study evaluated these potential associations by analyzing data from the National Health and Nutrition Examination Survey III (NHANES III), which documents the general health and nutritional status of randomly selected United States subjects from 1988 to 1994. METHODS: This cross sectional, retrospective study of the NHANES III database included a study population of 13,792 subjects > or = 20 years of age with at least 6 natural teeth. A history of bronchitis and/or emphysema was recorded from the medical questionnaire, and a dichotomized variable combined those with either chronic bronchitis and/or emphysema, together considered as chronic obstructive pulmonary disease (COPD). Subject lung function was estimated by calculating the ratio of forced expiratory volume (FEV) after 1 second (FEV1)/forced vital capacity (FVC). Oral health status was assessed from the DMFS/T index (summary of cumulative caries experience), gingival bleeding, gingival recession, gingival probing depth, and periodontal attachment level. Unweighted analyses were used for initial examination of the data, and a weighted analysis was performed in a final logistic regression model adjusting for age, gender, race and ethnicity, education, income, frequency of dental visits, diabetes mellitus, smoking, and alcohol use. RESULTS: The mean age of all subjects was 44.4 +/- 17.8 years (mean +/- SD): COPD = 51.2 +/- 17.9 years and subjects without COPD = 43.9 +/- 17.7 years. Subjects with a history of COPD had more periodontal attachment loss than subjects without COPD (1.48 +/- 1.35 mm versus 1.17 +/- 1.09 mm, P = 0.0001). Subjects with mean attachment loss (MAL) > or = 3.0 mm had a higher risk of COPD than those having MAL < 3.0 mm (odds ratio, 1.45; 95% CI, 1.02 to 2.05). A trend was noted in that lung function appeared to diminish with increasing periodontal attachment loss. CONCLUSIONS: The findings of the present analysis support recently published reports that suggest an association between periodontal disease and COPD. PMID- 11210074 TI - Detection of platelet-activating factor in gingival tissue surrounding failed dental implants. AB - BACKGROUND: Dental implant therapy has entered routine clinical practice. However, the failure rate of implants at 5 years, due to biological factors, is still around 7%. The pathogenesis of implant loss involves a complex network of cells and inflammatory mediators. This study evaluated platelet-activating factor (PAF), a potent phospholipid mediator of inflammation, in soft tissue surrounding failed dental implants versus healthy implants. METHODS: PAF was estimated on extracted lipids by bioassay on washed rabbit platelets; inflammatory cell populations were assessed semiquantitatively after staining, and microvessel density was evaluated after immunohistochemical staining. RESULTS: Biologically active PAF was detected in the lipid extracts of samples excised from gingival tissue of patients with failed implants, but not in samples from patients with osseointegrated implants or from healthy edentulous subjects. The amount of PAF detected in failed implants was significantly higher than in healthy implants, suggesting a local production of this mediator. CONCLUSIONS: The presence of PAF was associated with histopathological findings of local inflammation and increased blood vessel density. PMID- 11210075 TI - Fluid dynamics of gingival tissues in transition from physiological condition to inflammation. AB - BACKGROUND: An increase in gingival sulcular fluid filtration is a common clinical sign of early gingivitis. The aim of this study was to describe the fluid dynamics of the gingival interstitial tissues at the level of the sulcus in the transition towards inflammation. METHODS: In 13 anesthetized rabbits, a silk ligature was placed around incisors close to the gingival margin, in order to prevent mechanical cleaning of plaque deposition. After 2 to 7 days, animals were anesthetized and interstitial fluid pressure measured using glass micropipettes connected to a servonull pressure system at the level of the free and attached gingiva. RESULTS: Interstitial pressure was 3.8 +/- 2.9 cmH2O, significantly higher than the normal physiological value (about -1 cmH2O). Colloid osmotic pressure of interstitial fluid samples collected using the wick technique was measured using an osmometer whose membrane had a molecular cut-off of 30 kD and averaged 12.8 +/- 2.8 cmH2O (unchanged relative to control). Mean gingival sulcular fluid flow, measured by placing a PE tube (0.5 mm OD, 0.28 mm ID) in the sulcus, was 0.16 +/- 0.12 microl/h; the mean colloid osmotic pressure was 13.6 +/ 6.6 cmH2O, corresponding to a protein concentration of approximately 2.8 g/dl. Proteins of gingival fluid may leak from inflamed gingival interstitium or derive from bacteria of dental plaque. Histological analysis of gingival biopsies showed neutrophilic polymorphonuclear leukocyte infiltrates in both the dermis and epidermis layer. CONCLUSIONS: Based on hydraulic and colloid osmotic data, the Starling pressure gradient favored filtration from gingival interstitium to the sulcular space, a condition opposite to that observed in healthy gingiva where fluid filtration is absent. PMID- 11210076 TI - Relationship of sulcular sulfide level to severity of periodontal disease and BANA test. AB - BACKGROUND: Volatile sulfur compounds (VSC), such as hydrogen sulfide and methyl mercaptan, are toxic metabolites produced by periodontal pathogens. Their relationship to periodontal disease severity is not yet fully understood. Hence, the aims of this study were to: 1) examine the relationship between sulcular sulfide (pS) levels and severity of periodontal disease and 2) examine the link between pS level and the BANA (benzoyl-DL-arginine-naphthylamide) test. METHODS: Seventy systemically healthy subjects with a mean age of 53.0 +/- 13.8 years participated. Three sites were selected from each subject based upon radiographic bone loss (RBL): RBL < 2 mm, healthy; RBL > or = 2 to < 4, low to moderate; RBL > or = 4 mm, severe. Periodontal parameters, probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP), were recorded. The pS level was measured using a portable sulfide monitor in a digital score ranging from 0.0 (< 10(-7) M of S) to 5.0 (> or = 10(-2) M of S) in increments of 0.5. The presence of specific bacteria in subgingival plaque was detected using BANA test. RESULTS: The mean pS level was 0.10 +/- 0.23, 0.36 +/- 0.48, and 1.10 +/- 0.87 for healthy, low to moderate, and severe disease sites, respectively, and was statistically different (P<0.001). The pS level was positively correlated with the BANA test, and was higher in untreated subjects than maintenance subjects (P<0.01). CONCLUSIONS: The pS level may be a potential indicator for detecting severity of periodontal disease and identifying bacteria that are capable of hydrolyzing BANA. PMID- 11210077 TI - Relationship between sulcular sulfide level and oral malodor in subjects with periodontal disease. AB - BACKGROUND: The relationship between oral malodor and sulfide levels in periodontal pockets (pS) has not yet been determined. The aims of this study were: 1) to identify the correlation among oral malodor, pS levels, and the BANA (benzoyl-DL-arginine-naphthylamide) test and 2) to recognize the interaction between oral malodor, demographic factors, tongue coating, and periodontal condition. METHODS: Eighty-one periodontal patients participated in this study. A portable sulfide monitor and organoleptic method were used to evaluate oral malodor. Demographic data included age, gender, race, and smoking habits. The volume of tongue coating and periodontal condition for all teeth were assessed. The pS levels of 3 different radiographic bone loss (RBL) sites: RBL < 2 mm, healthy; RBL > or = 2 to < 4 mm; low to moderate; RBL > or = 4 mm, severe, were measured using an industrial sulcular sulfide-monitoring device. Subgingival plaque samples from the above 3 sites and tongue scraping were examined by the BANA test. RESULTS: The volume of tongue coating (P<0.001), extent of periodontal disease (P<0.05), pS levels of the sites with low to moderate bone loss (P<0.05), and BANA score of tongue scrapings (P<0.05) were significantly associated with oral malodor. Stepwise multiple regression analysis examined the degree of association between oral malodor and potential explanatory variables. The volume of tongue coating and percent of sites BOP (bleeding on probing) were significantly associated with oral malodor. Females and smoking habit were negatively correlated with organoleptic measurements. CONCLUSIONS: The pS level of the representative sites with low to moderate bone loss demonstrated a modest association with oral malodor. Oral malodor in periodontal patients was primarily associated with tongue coating and gingival inflammation. PMID- 11210078 TI - Interactions of lymphotoxin alpha (TNF-beta), angiotensin-converting enzyme (ACE), and endothelin-1 (ET-1) gene polymorphisms in adult periodontitis. AB - BACKGROUND: Adult periodontitis is a complex multifactorial disease whose etiology is not well defined. To investigate whether the genes encoded within the HLA class III region may confer susceptibility to periodontitis, polymorphisms in the ET-1 and TNF-beta genes were analyzed together with the I/D polymorphism of the ACE gene. METHODS: We determined allele and genotype frequencies of the NcoI bi-allelic polymorphism of the TNF-beta gene, the I/D (insertion/deletion) polymorphism of the ACE gene, and the TaqI polymorphism of the ET-1 gene in 63 Caucasian patients with adult periodontitis and 95 orally healthy controls. RESULTS: We found a significant difference in a 3 locus combination of genotypes between patients and controls (P<0.05). In the next analyses, no significant differences were found in allele frequencies of single genes, but we did find a significant difference in the genotype distribution between cases and controls for TNF-beta (P<0.03). Differences were also observed for 2 locus combinations of ACE and TNF-beta genotypes (P<0.03), and the ET-1 and TNF-beta (P<0.05) genes. Evidence of deviation from Hardy-Weinberg equilibrium was observed in the periodontitis group for TNF-beta, with an absence of the B1B1 homozygotes in patients. CONCLUSIONS: This study is of an exploratory nature. Considering the number of significant results, however, at least a part of the observed associations may obviously be real and our findings suggest that interactions of the TNF-beta, ET-1, and ACE genes may be involved in susceptibility to adult periodontitis. PMID- 11210079 TI - Tobacco smoking and neutrophil activity in patients with periodontal disease. AB - BACKGROUND: Tobacco smoking has considerable negative effects on periodontal health. The mechanisms behind these effects are incompletely understood but may be related to the host response. The aim of the present study was to investigate the influence of tobacco smoking on the gingival crevicular fluid (GCF) levels of elastase, lactoferrin (LF), alpha-1-antitrypsin (alpha-1-AT), and alpha-2 macroglobulin (alpha-2-MG) under periodontally diseased conditions. METHODS: The study population included 15 smokers (5 women and 10 men) aged 34 to 69 years and 17 non-smokers (5 women and 12 men) aged 31 to 81 years. Clinical registration of gingival index (GI), plaque index (PI), probing depth, as well as sampling of GCF were made at 3 sites with severe lesions and 3 sites with moderate lesions in each individual. The elastase activity was measured with a chromogenic low molecular substrate and the LF, alpha-1-AT, and alpha-2-MG concentrations with ELISA. RESULTS: The results showed that, with regard to severe lesions, smokers had a significantly lower concentration of alpha-2-MG as well as significantly lower total amounts of alpha-2-MG and alpha-1-AT than non-smokers. With regard to moderate lesions, smokers tended to exhibit a lower concentration of alpha-2-MG, but the difference was not statistically significant. Comparing moderate and severe lesions, smokers exhibited no gradual increase with disease severity in contrast to non-smokers, who showed significantly or almost significantly increased levels of LF and alpha-2-MG in severe as compared to moderate lesions. CONCLUSIONS: The present results indicate that the levels of alpha-2-MG and alpha 1-AT are suppressed in smokers with periodontitis, suggesting that smoking interferes with these protease inhibitors. This may be one mechanism by which smoking affects the inflammatory response. PMID- 11210081 TI - Congenital adrenal hyperplasia: from genetics and biochemistry to clinical practice, Part 1. AB - Congenital adrenal hyperplasia (CAH) refers to a group of genetic disorders with defects in the synthesis of cortisol. The synthesis of other steroids such as mineralocorticoids and adrenal/gonadal sex steroids may also be affected. The clinical presentation of the various forms of CAH depend on the following: (1) the affected enzyme, (2) the residual enzymatic activity, (3) the physiologic consequences of deficiencies of the end-products and excess of precursors. The first part of this two-part review discusses the genetics, biochemistry, and clinical presentation of the different forms of CAH. Understanding the genetics and pathophysiology of each of the various enzyme mutations is essential for the evaluation and management of the different clinical forms of CAH. PMID- 11210080 TI - A multidisciplinary approach to the diagnosis and treatment of early-onset periodontitis: a case report. AB - BACKGROUND: The diagnosis and treatment of early-onset forms of periodontitis (EOP) represent a major challenge to periodontists. In this case report, we describe a multidisciplinary approach for the treatment of a patient with severe generalized juvenile periodontitis (GJP). Our approach incorporates clinical laboratory evaluation with conventional concepts of periodontal pathogenesis and therapeutics to diagnose and effectively treat EOP. METHODS: The 17-year-old female patient presented with clinical and radiographic evidence of severe attachment loss. Microbiological testing showed the presence of known periodontal pathogens including Actinobacillus actinomycetemcomitans, Prevotella intermedia, and Porphyromonas gingivalis. Routine immunological tests did not reveal any of the functional defects thought to play a role in the pathogenesis of EOP After initiation of therapy, which consisted of scaling and root planing, supplemented with administration of systemic antibiotics, a reduction in probing depth and gain in clinical attachment could be demonstrated. Microbiological testing was used to monitor the composition of the periodontal microbiota and to adjust antimicrobial therapy accordingly. RESULTS: Using a non-surgical approach to treatment, except for 2 root amputations performed without flap reflection, we have been able to stabilize this patient's periodontal condition over the course of a 2-year follow-up period. CONCLUSIONS: This treatment strategy provides an efficacious alternative to more aggressive forms of therapy and should therefore be considered for the treatment of patients with severe EOP. PMID- 11210082 TI - Characteristics of women pediatricians. AB - To contrast women pediatricians (n = 807) with other U.S. women physicians, we used data from the Women Physicians' Health Study, a national, randomly sampled questionnaire survey (total n = 4,501). Compared with other women physicians, women pediatricians worked less and reported lower incomes but also reported less work stress and less career dissatisfaction. Pediatricians were less likely to counsel/perform screening regarding cholesterol, HIV, smoking, and alcohol but more likely regarding skin cancer or sunscreen use, nutrition, and weight. Given current emphases on trying to improve U.S. children's health practices, these findings are of concern. PMID- 11210083 TI - Frequent breastfeeding and food refusal associated with failure to thrive. A manifestation of the vulnerable child syndrome. AB - This paper acquaints pediatricians and health care personnel with the triad of poor weight gain, frequent breastfeeding, and food refusal in infants during the second 6 months of life. The histories of six infants aged 8-11 months, with failure to thrive, food refusal, and frequent breastfeeding, are presented. All the mothers were facing significant stresses, which may have decreased their breast milk supply, and were leading them to use breastfeeding for their comfort and/or the comfort of their infant. The infants responded with continued frequent breastfeeding, refusal of complementary foods, and decreased weight gain. These infants fit the characteristics of the vulerable child syndrome. Treatment of these infants required evaluation and treatment of the mothers' psychosocial issues along with a behavioral feeding program. Even with this multidisciplinary approach, these infants showed very slow catch-up growth. Pediatricians and health care personnel should use and build on this information in the evaluation and treatment of infants with similar problems. PMID- 11210084 TI - Do parents choose appropriate automotive restraint devices for their children? AB - This study aims to describe parental choices of childhood automotive restraints and compare them with guidelines based on weight and height. Parents were surveyed and their children's heights and weight were measured. Results indicated that many parents believed their child fit a lap or shoulder belt when their children were too short to fit these devices. For children weighing < 40 pounds, 45% of parents believed the lap belt fit. Thirteen percent of 4-7-year-olds used booster seats, appropriate for 72% by sitting height criteria; and 33% of children < or = 7 years used the lap/shoullder belt, appropriate for 8% by sitting height criteria. Implications are that parental perceptions of fit may lead to inappropriate restraint choices for children. Practitioners should discuss child restraint use with parents in the context of their child's weight and height. PMID- 11210085 TI - An asymptomatic infant with a neck mass. PMID- 11210086 TI - Dural sinus thrombosis complicating hypernatremic dehydration in a breastfed neonate. PMID- 11210087 TI - Fever-induced protracted ballismus in choreoathetoid cerebral palsy. PMID- 11210088 TI - Stress-induced movement disorders. PMID- 11210089 TI - Respiratory support of children with a retropharyngeal abscess with nasal CPAP. PMID- 11210090 TI - Assessing growth patterns. PMID- 11210091 TI - Severe acute renal failure due to hemoglobinuria after use of WinRho for the treatment of idiopathic thrombocytopenic purpura. PMID- 11210092 TI - Clinical significance of ventilation/perfusion scans in collagen disease patients. AB - The purpose of this study was to detect disturbances in pulmonary circulation in collagen disease patients by means of a non-invasive technique. METHODS: Ventilation/perfusion scans with 133Xe gas and 99mTc-macroaggregated albumin (MAA) were performed in 109 patients with various collagen diseases. Functional images of V, Vol, Q and V/Q ratio were obtained at total lung capacity. Wash-out time was calculated from the wash-out curve. Whole body scans were performed in 65 patients to evaluate intra-pulmonary shunts. RESULTS: Increased V/Q areas were observed in 74 patients (67.9%), suggesting some impairment of pulmonary perfusion. Decreased perfusion, probably due to vasculitis or intravascular microcoagulation, was observed often, even in patients without pulmonary fibrosis. Shunt ratios over 10% were observed in 8 of the 65 patients (12.3%), indicating formation of PA-PV shunts secondary to peripheral vascular impairment. Wash-out time was prolonged in 37 patients (33.9%), shortened in 18 (16.5%), and within the normal range in 54 (49.6%). The prolonged and normal wash-out times in the patients with pulmonary fibrosis may represent obstructive changes in the small airways superimposed on the fibrosis. CONCLUSION: Ventilation/perfusion scans are a very useful tool for evaluating collagen lung diseases, and they might contribute to treatment decisions for the patients. PMID- 11210093 TI - Technetium-99m MIBI single photon emission computed tomography as an indicator of prognosis for patients with lung cancer-preliminaly report. AB - PURPOSE: We performed technetium-99m hexakis-2-methoxyisobutylisonitrile (Tc-99m MIBI) single photon emission computed tomography (SPECT) in 23 patients with primary lung cancer between July 1993 and March 1996. We evaluated the relationships among the uptake ratio, retention index and the prognosis after radiation therapy and/or chemotherapy. MATERIALS AND METHODS: Tc-99m MIBI SPECT was performed at 30 minutes and at 3 hours after intravenous injection of 600 MBq of Tc-99m MIBI with three gamma camera detectors (GCA-9300A/HG) on transverse SPECT images. Regions of interest were set in the area of abnormal uptake of Tc 99m MIBI and in the contralateral normal lung. The ratio of uptake in the lesion to that in the contralateral normal lung was obtained on early images (early ratio; ER) as well as delayed images (delayed ratio: DR). The retention index (RI) was calculated as follows: RI = (DR - ER)/ER x 100. The ratio was compared with survival time and prognostic factors. RESULTS: There was no correlation between ER and DR. The patients with high RI survived longer than those with low RI (median survival, 19.4 months vs. 9.4 months; p = 0.0104 by the Mantel-Cox test). CONCLUSION: These results suggest that RI is the most useful among Tc-99m MIBI indices of primary lung cancer in predicting prognosis. PMID- 11210094 TI - Comparison of Emory and Cedars-Sinai methods for assessment of left ventricular function from gated myocardial perfusion SPECT in patients with a small heart. AB - To evaluate the effect of left ventricular (LV) size on the calculation of LV function from gated myocardial SPECT with Emory and Cedars-Sinai programs, we performed 99mTc-tetrofosmin gated SPECT on 49 patients with ischemic heart disease. End-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF) were semi-automatically calculated by each program. All patients underwent left ventriculography (LVG) within 3 months before and after the SPECT study. We grouped the patients into 22 with a calculated ESV obtained from LVG of over 50 ml (group A) and 27 with an ESV value of 50 ml or below (group B). We then compared the ESV values from gated SPECT with those from LVG in each group. In group A, the ESV from both Emory and Cedars-Sinai programs similarly correlated well with those from LVG (r = 0.92 and r = 0.93, respectively), but in group B, the ESV calculated from the Cedars-Sinai program correlated less with those from LVG (r = 0.53) than those from the Emory program did (r = 0.70). The calculated LV volumes had more errors in the Cedars-Sinai program than in the Emory program, when a patient had a small heart. PMID- 11210095 TI - Relation between myocardial response to dobutamine stress and sympathetic nerve activation in patients with idiopathic dilated cardiomyopathy: a comparison of 123I-MIBG scintigraphic and echocardiographic data. AB - It is likely that a close association exists between findings obtained by two methods: dobutamine stress echocardiography and 123I-MIBG scintigraphy. Both of these methods are associated with beta-adrenergic receptor mechanisms. This study was conducted to demonstrate the relation between myocardial response to dobutamine stress and sympathetic nerve release of norepinephrine in the failing heart. In 12 patients with heart failure due to idiopathic dilated cardiomyopathy, the myocardial effects of dobutamine stress were evaluated by low dose dobutamine stress echocardiography: and sympathetic nerve function was evaluated by scintigraphic imaging with iodine-123 [123I] meta iodobenzylguanidine (MIBG), an analogue of norepinephrine. Echocardiography provided quantitative assessment of wall motion and left ventricular dilation; radiotracer studies with 123I-MIBG provided quantitative assessment of the heart to-mediastinum (H/M) uptake ratio and washout rate. Results showed that H/M correlated with baseline wall motion (r = 0.682, p = 0.0146), wall motion after dobutamine stress (r = 0.758, p = 0.0043), the change in wall motion (r = 0.667, p = 0.0178), and with left ventricular diastolic diameter (r = 0.837, p = 0.0007). In addition, the 123I-MIBG washout rate correlated with baseline wall motion (r = 0.608, p = 0.0360), wall motion after dobutamine stress (r = 0.703, p = 0.0107), and with the change in wall motion (r = 0.664, p = 0.0185). Wall motion, especially in the myocardial response to dobutamine stress, is related to sympathetic nerve activity in heart failure. PMID- 11210096 TI - A new method to estimate rCBF using IMP and SPECT without any blood sampling. AB - We developed and evaluated a method to measure rCBF without any blood sampling by using iodine- 123 IMP and SPECT. An integral of arterial input function, the integral taken from the value 0 to T of the variable Ca(t)dt, can be expressed as TC(T)/CO, where TC(T) is radioactivity delivered to the body in T minutes and CO is cardiac output. If T is acceptably small, rCBF can be determined by means of a microsphere model analysis with IMP as Cb(T)/(TC(T)/CO), where Cb(T) is cerebral radioactivity at T minutes. We derived TC(T) and CO from a chest dynamic scan. The method was applied to 45 patients who underwent rCBF studies (58 studies) with arterial blood sampling (ABS). Data from the chest scan were analyzed in comparison with ABS data in the first 28 studies, and equations for correction yielding an accurate TC(T)/CO were derived. The validity of the proposed method was evaluated in the subsequent 30 studies. The method yielded rCBF (rCBF-test) which agreed well with rCBF obtained by a two-compartment model analysis of dynamic SPECT and ABS data (rCBF-ref) with the mean and SD of differences between rCBF-test and rCBF-ref being 1.0 and 2.7 ml/100 g/min, respectively. In eleven subjects who underwent more than two studies, a percentage change in rCBF-test between the studies also closely approximated that of rCBF-ref (y = 1.11 x + 2.63, r = 0.92). The method can be used with acceptable reliability to measure rCBF without any blood sampling. PMID- 11210097 TI - Double-injection method for sequentially measuring cerebral blood flow with N isopropyl-(123I)p-iodoamphetamine. AB - We investigated the accuracy of a double-injection method for sequentially measuring cerebral blood flow (CBF) with N-isopropyl-(123I)p-iodoamphetamine (IMP) in simulation studies based on patient data and in clinical studies. The unidirectional clearance of IMP from the blood to the brain (K1; nearly equal to CBF) in the first and second sessions was calculated by means of a microsphere model. The K1 values in the first session (K1I) were calculated from Cb(5)/Int_CaI, where Cb(5) and Int_CaI are values for brain radioactivity 5 min after the first injection and for arterial blood radioactivity obtained by 5-min continuous sampling. The K1 values in the second session (K1II) were calculated by means of the following four methods. Method 1: [Cb(tz + 5) - Cb(tz)]/[Int_CaII - Ca(tz) x 5], where Cb(tz+5) and Cb(tz) are the brain radioactivity levels 5 min after the second injection and at the time the second session was started (tz), respectively. Int_CaII and Ca(tz) are the arterial blood radioactivity levels obtained by 5-min continuous sampling after the second injection and at tz, respectively. Method 2: [Cb(tz + 5) - Cb(tz)]/[Int_CaI x R], where R is the injection dose ratio. Method 3: [Cb(tz + 5) - Cb(tz) x exp(- K1I x 5/lambda)]/Int_CaII, where lambda is the population averaged partition coefficient. Method 4: same as Method 3 except that K1I was replaced by K1II obtained by means of Method 2. Theoretically, Method 4 appeared to be the best of the four methods. The change in K1 during the second session obtained by Method 1 or 2 largely depended on R and tz, whereas Method 3 or 4 yielded a more reliable estimate than Method 1 or 2, without largely depending on R and tz. Since Method 2 was somewhat superior to other methods in terms of noninvasiveness and simplicity, it also had the potential for routine clinical use. The reproducibility of two sequential measurements of K1 was investigated with clinical data obtained without any intervention. The response of CBF to acetazolamide challenge was also assessed by the above four methods. The knowledge gained by this study may assist in selecting a method for sequentially measuring CBF with a double injection of IMP. PMID- 11210098 TI - Simultaneous assessment of Tc-99m-sestamibi and I-123-BMIPP myocardial distribution in patients with myocardial infarction: evaluation of left ventricular function with ECG-gated myocardial SPECT. AB - 123I-labeled 15-(p-iodophenyl)-3R,S-methyl pentadecanoic acid (BMIPP) is a branched-chain free fatty acid that is used to evaluate various cardiac diseases. The aim of the present study was to investigate the relationship between myocardial perfusion (99mTc-sestamibi) and BMIPP uptake, and to correlate perfusion and metabolic alterations with regional left ventricular dysfunction in patients with myocardial infarction (MI). ECG-gated dual-isotope myocardial SPECT was performed on 130 patients with MI with sestamibi (555 MBq) and BMIPP (148 MBq). The patients were classified into 3 groups according to PTCA therapy and the interval between the onset of infarction and RI injection (OR time). Group A (n = 56) included patients whose OR time was less than one month and who had undergone successful PTCA, Group B (n = 36) had OR times of less than one month and had conservative medical therapy, and Group C (n = 38) had OR times of over one month. The severity scores of the dual-isotope images were calculated from the defect scores in 9 segments. From the ECG-gated SPECT data with sestamibi, the left ventricular ejection fraction (LVEF; %) and regional wall motion were determined automatically using the QGS program LVEF obtained from gated SPECT correlated well with the severity scores for sestamibi and BMIPP (r = -0.68 and 0.76, respectively). The delta severity scores (BMIPP scores - sestamibi scores) of Group A were significantly higher than those of the other two groups (3.6 +/- 3.0 vs. 1.5 +/- 1.7 and 1.0 +/- 1.4, p < 0.001 ). The rate of dysfunctional segments with normal sestamihi distribution was significantly higher in Group A than in Group C (20.7% vs. 6.7%, p < 0.001). ECG-gated dual-isotope SPECT is useful since myocardial perfusion, fatty acid metabolism and left ventricular function can be analyzed during a single examination, so that this procedure has the potential to provide comprehensive information when evaluating patients with ischemic heart disease. PMID- 11210099 TI - Search for PET probes for imaging the globus pallidus studied with rat brain ex vivo autoradiography. AB - We have evaluated the feasibility of using four positron emission tomography (PET) tracers for imaging the globus pallidus by ex vivo autoradiography in rats. The tracers investigated were [11C]KF18446, [11C]SCH 23390 and [11C]raclopride for mapping adenosine A2A, dopamine D1 and dopamine D2 receptors, respectively, and [18F]FDG. The highest uptake by the globus pallidus was found for [11C]SCH 23390, followed by [18F]FDG, [11C]KF18446 and [11C]raclopride. The receptor specific uptake by the globus pallidus was observed in [11C]KF18446 and [11C]SCH 23390, but not in [11C]raclopride. Uptake ratios of globus pallidus to the striatum for [18F]FDG and [11C]KF18446 were approximately 0.6, which was twice as large as that for [11C]SCH 23390. In a rat model of degeneration of striatopallidal gamma-aminobutyric acid-ergic-enkephalin neurons induced by intrastriatal injection of quinolinic acid, the uptake of [11C]KF18446 by the striatum and globus pallidus was remarkably reduced. To prove the visualization of the globus pallidus by PET with [18F]FDG and [11C]KF18446, PET-MRI registration technique and advances in PET technologies providing high-resolution PET scanner will be required. The metabolic activity of the globus pallidus could then be measured by PET with [18F]FDG, and [11C]KF18446 may be a candidate tracer for imaging the pallidal terminals projecting from the striatum. PMID- 11210100 TI - Assessment of liver function in chronic liver diseases and regional function of irradiated liver by means of 99mTc-galactosyl-human serum albumin liver scintigraphy and quantitative spectral analysis. AB - Scintigraphy with 99mTc-diethylenetriamine pentaacetic acid galactosyl human serum albumin (99mTc-GSA) was performed on 102 patients, then the hepatic extraction fraction (HEF), the rate constant for liver uptake of the tracer from the blood (K1) and the hepatic blood flow index (HBFI) were determined by spectral analysis. The HEF, K1 and HBFI values correlated moderately or closely with various indices of hepatic function, and the HEF and K1 values decreased according to the stage of liver dysfunction. The HEF and K1 values linearly and nonlinearly correlated with HH15 and LHL15, respectively. The HEF, K1 and HBFI values for the irradiated portion of 20 patients before and alter irradiation were compared. The HEF value in patients with a cirrhotic liver significantly (p < 0.002) decreased compared with that in patients with a normal liver at a dose of less than 40 Gy, whereas the HBFI value in patients with a normal liver significantly (p < 0.05) decreased compared with that in patients with a cirrhotic liver at a dose of 40 Gy or greater. This method appears to be a simple, non-invasive and useful tool with which to quantitatively evaluate liver function and it also helps clarify changes in regional function of the irradiated liver. PMID- 11210101 TI - Nontumorous decrease in Tc-99m GSA accumulation. AB - Nontutimorous decrease in 99mTc-GSA accumulation has not been well covered in the literature. Understanding of this phenomenon is, however, essential for accurate evaluation of regional hepatic function. Scintigrams (transaxial SPECT) of 269 patients who underwent 99mTc-GSA liver scintigraphy were reviewed for the presence of nontumorous decreases in 99mTc-GSA accumulation. Nontumorous decreases in 99mTc-GSA accumulation were seen in 32 of 269 patients (12%). In 16 of the 32 patients (6%), nontumorous decreases in 99mTc-GSA accumulation corresponded to regional decrease in portal venous flow. The causes of such decrease in portal venous flow were portal thrombus of hepatocellular carcinomas in eight patients, portal venous stenosis or occlusion by hilar cholangiocarcinomas in five patients, inter alia. In eight patients (3%), the regions with decreased 99mTc-GSA accumulation correlated with massive hepatic necrosis in fulminant hepatitis, scar in hepatitis, or confleuent in portal venous flow, lobar biliary stasis, or both. In four patients (1.5%), the exact causes of nontumorous decrease in 99mTc-GSA accumulation could not be determined. PMID- 11210102 TI - Discordant uptake of Tc-99m PMT and Tc-99m GSA by two hepatocellular carcinoma lesions. AB - Tc-99m PMT and Tc-99m GSA can be taken up by hepatocellular carcinoma (HCC), but there has been no report concerning HCC showing accumulation of both of Tc-99m PMT and Tc-99m GSA. In this paper we describe a case of two simultaneously developed HCCs, one of which took up both tracers but the other took up neither of them. PMID- 11210103 TI - A method for identifying underlying causes of death in epidemiological study. AB - To obtain the underlying causes of death in individuals of a cohort (male only), the items of date of birth, date of death and address code at the time of death were linked between the data of resident cards and the death tapes of National Vital Statistics supplied by the Ministry of Health and Welfare. As a result, the persons who have the same information for above mentioned three items between the resident cards and the death tapes accounted for 97.4%. If the persons who had the same information for three items except one item were considered to be identical, they accounted for 99.4%. It would be concluded that underlying cause of death can be obtained by record linkage of death tapes of National Vital Statistics with three informations in residence cards, dates of birth, dates of death and address codes at the time of death, even without names of the individual in the death tapes. The matched rate would be high enough for epidemiological studies. PMID- 11210104 TI - Relationships between cigarette smoking, alcohol drinking, the ALDH2 genotype and adenomatous types of colorectal polyps in male self-defense force officials. AB - Alcohol drinking as well as cigarette smoking has been associated with development of colorectal polyps, Asians such, as Japanese, Chinese and Korean have high frequency of genetic polymorphism in low Km aldehyde dehydrogenase (ALDH2) gene which greatly regulates alcohol intake. In the present study, we investigated associations of this polymorphism and lifestyles with colorectal polyps in self-defense forces personnels in Japan. All subjects received colonoscopy at a retirement health examination. The ALDH2 genotype was determined using polymerase chain reaction and restriction fragment length polymorphism method. Frequency of the ALDH2 genotype was not different between those with colorectal polyps (n=69) and those without the polyps (n=131). Smoking was associated with development of colorectal polyps (OR=4.7, 95% confidence interval=1.9-11.5) in the ALDH2 proficient genotype. The association appeared to be enhanced by drinking alcohol since a synergistic effect of smoking and alcohol drinking (> or =60 ml/day) was indicated (OR=9.9, 95% confidence interval=2.9 34.1) by logistic regression analysis. In the ALDH2 deficient genotype, however, we could not evaluate interactions of smoking and alcohol drinking on colorectal polyp development because of the small sample size of heavy alcohol drinkers. The genotype analysis would be useful in evaluating effects of environmental factors on outcomes for each genetically defined subpopulation. PMID- 11210105 TI - Mortality among persons with a history of Kawasaki disease in Japan: existence of cardiac sequelae elevated the mortality. AB - OBJECTIVE: To clarify whether patients with Kawasaki disease have a higher death rate than the age-matched healthy population after the disease occurrence. STUDY DESIGN: Between July 1982 and December 1992, 52 collaborating hospitals collected data on all patients having a new definite diagnosis of Kawasaki disease. Patients were followed until December 31, 1997, or death. The expected number of deaths was calculated from Japanese vital statistics data and compared with the observed number. RESULTS: Of 6576 patients enrolled, 25 (19 males and 6 females) died. The standardized mortality ratio (SMR) was 1.35. In spite of the high SMRs during acute phase, the mortality rate was not high after the acute phase for all patients. Although the SMR after the acute phase was 0.76 for those without cardiac sequelae, 6 males (no females) with cardiac sequelae died during this period and the SMR for the male group with cardiac sequelae was 2.77. CONCLUSION: The mortality rate among males with cardiac sequelae due to Kawasaki disease was 2.8 times as high as in general population, whereas mortality rates for females with the sequelae and both males and females without sequelae were not elevated. PMID- 11210106 TI - A reproductive health survey on unintended pregnancy in Yamagata, Japan: feasibility of the survey and test-retest reliability and validity of a questionnaire. AB - We have designed a survey to investigate factors related to unintended pregnancy using a newly devised questionnaire. This pilot study was conducted to examine the feasibility of the study and the test-retest reliability and the validity of the questionnaire. Samples were 107 cervical and breast cancer screening participants aged 35-49 year-old in 1999 in Yamagata, Japan. The same questionnaires were mailed twice to examine the test-retest reliability. Women's medical records for cancer screening were used to examine the validity of the questionnaire. Ninety-six women agreed to participate in the study and 89.6% of them responded to the first survey. The agreements between two surveys were substantial to perfect for the nominal and ordinal data, and for the continuous data, the standard deviations (SDs) were less than 1 and the correlation coefficients were over 0.6. The comparison between medical record and questionnaire derived data showed perfect agreements for reproductive items except age at last birth (SD: 0.71, correlation coefficient: 0.97), and fair agreements for drinking and smoking habits. Obtaining information on unintended pregnancy by questionnaire is feasible, and the test-retest reliability and the validity of the questionnaire are satisfactory. Currently we are conducting a survey with a larger sample. PMID- 11210107 TI - Gender differences in the association between psychosocial factors and depressive symptoms in Japanese junior high school students. AB - To determine psychosocial factors associated both with depressive symptoms and with gender differences in depressive symptoms among junior high school students, we conducted self-administered questionnaires using a sample of 2,660 students of 13 public junior high schools in Okinawa, Japan. Depressive symptomatology was measured by the Center for Epidemiologic Studies Depression Scale (CES-D). The psychosocial variables examined were life stresses, social support, health practices, self-esteem, and locus of control. Depressive symptoms were positively associated with life stresses and negatively associated with health practices, social support, self-esteem, and internal locus of control. In addition, female students were likely to report more depressive symptoms, life stresses, and low self-esteem and poor health practices. After controlling for the psychosocial variables differed by gender, gender differences in depressive symptoms were eliminated. In conclusion, for depressive symptoms of junior high school students, life stresses might be risk factors, but positive health practices, social support, high self-esteem, and internal locus of control might be protective factors. Gender differences in depressive symptoms could be explained by the females' elevation on these psychosocial variables. PMID- 11210108 TI - Seasonal variation in mortality from ischemic heart disease and cerebrovascular disease in Okinawa and Osaka: the possible role of air temperature. AB - Okinawa is located in a subtropical area and is well-known for low mortality due to ischemic heart disease (IH-D) and cerebrovascular disease (CVD). However, the factors that contribute to these low mortality rates remain unclear. We examined the seasonal variation in the mortality due to IHD and CVD among Okinawa and Osaka residents, aged 45 to 84 years, between 1992 and 1996. In addition, we studied if there was a relationship between the monthly mortality rate from IHD or CVD and the monthly mean daily air temperature in Naha City and Osaka City. Data on the monthly mean daily air temperature was obtained from the meteorological stations in Naha City and Osaka City. Our results showed that there were inverse correlations between the monthly mean daily temperature in a city and each of the monthly mortality from IHD in Okinawa (r=-0.794, p<0.01), the monthly mortality from CVD in Okinawa (r=-0.837, p<0.001), and the monthly mortality from CVD in Osaka (r=-0.954, p<0.001). In Osaka, the monthly mortality rate from IHD was at or near its minimum value when the mean daily temperature was approximately 25 degrees C (in September), and it increased in a linear fashion as the mean monthly temperature fell (r=-0.975, p<0.001). The difference between the monthly mortality from IHD or CVD among the Okinawa and the Osaka residents increased in the winter season in comparison with that in the other seasons, with the exception for IHD in July and in August. These findings indicate that the lower mortality from IHD and CVD in Okinawa is affected, at least in part, by Okinawa's warm winter. PMID- 11210109 TI - A case-control study of Creutzfeldt-Jakob disease in Japan: transplantation of cadaveric dura mater was a risk factor. AB - A case-control study was conducted to reveal the relative risk of cadaveric dura mater graft transplantation for Creutzfeldt-Jakob disease. Fifty-two cases with Creutzfeldt-Jakob disease that were reported to the surveillance of the disease, and 102 age- and sex-matched hospital controls were selected. Information on family history, occupations, and medical history was collected. Eight cases and no control had a history of cadaveric dura mater graft transplantation. Surgical operations without the dura mater graft, blood transfusion, and acupuncture did not elevate the risk. PMID- 11210110 TI - Does hyperuricemia affect mortality? A prospective cohort study of Japanese male workers. AB - A positive association between hyperuricemia and cardiovascular disease has been reported, but no study has evidenced yet the precise role of serum uric acid in the development of cardiovascular disease. In addition, no epidemiological studies have so far documented a decreased risk of cancer among people with hyperuricemia, even though the antioxidant action of uric acid has recently been stressed to inhibit DNA damage. The present prospective cohort study investigates the relationship between hyperuricemia and health hazards in a Japanese working population. The subjects were 49,413 Japanese male railroad workers, aged 25-60 years at enrollment. Serum uric acid and other baseline data were provided by annual health-survey records from 1975 to 1982. The vital status of the subjects was traced until the end of 1985 for those who remained alive. During an average 5.4-year study period, 984 deaths were recorded. Those with serum uric acid over 8.5 mg/dl showed elevated relative risks (RRs) of death in all causes (RR 1.62, p<0.01), coronary heart disease ( RR 1.52), stroke (RR 2.33, p<0.01), hepatic disease (RR 3.58, p<0.01), and renal failure ( RR 8.52, p<0.01), as compared with those with serum uric acid levels of 5.0-6.4mg/dl. The RR of death in all causes still remains statistically significant when adjusted by age and serum total cholesterol (2.00, p<0.01), age and alcohol intake (1.85, p<0.001), age and smoking (1.69, p<0.001), age and gout treatment (1.61, p<0.05), and also age and BMI (1.50, p< 0.05). On the other hand, the RR of all causes decreased but was still above 1.0 when adjusted by age and blood glucose (1.62), age and systolic blood pressure (1.32), age and GOT (1.23), and also age and history of cardiovascular disease (1.17). These results showed that hyperuricemia has a strong association with the RRs of death in all causes, coronary heart disease, stroke, hepatic disease and renal failure, and indicated that serum uric acid seems to be a considerable risk factor for reduced life expectancy. PMID- 11210111 TI - Prevalence of HBV infection among the healthy Nepalese males: a serological survey. AB - Sera from 478 healthy Nepalese male population, inhabiting various districts of five development regions of Nepal were collected from October 1996 to March 1997 and examined for the presence of HBsAg by third generation ELISA and Latex agglutination test in the laboratory of Central Department of Microbiology, Tribhuvan University, Kirtipur. The surface antigen was detected by ELISA in 4.0% (19/478) of subjects studied. However, different results were obtained in Latex agglutination test. The correlation between the results obtained from these two different tests is statistically significant (chi2=85.11, P<0.05). The results obtained from ELISA showed the probability of Nepal to fall in WHO category of intermediate endemicity zone for hepatitis B infection. The percent positivity of HBsAg was found to increase steadily from Eastern (2%) to Far Western (6.2%) development regions. Among the districts studied, Kailali district gave characteristically high prevalence followed by Rukum and Kaski. Other, districts representing for the prevalence are Sankhuwasabha, Jhapa, Ramechhap, Sarlahi, Dhanusa, Baglung, Gulmi, Palpa and Dang. None of the samples represented from Kathmandu valley were positive for HBsAg. The age groups of 16-20 years and 36-40 years were found to be associated with the hepatitis B infection. Furthermore, various percent prevalence of the infection were encountered from 16 to 40 years subjects and a single case was also observed from 63 years old man. All the samples recorded positive for HBsAg from ELISA were assayed for the amount of ALT as a liver function test. Where, 15.8% (3/19) of the infected subjects had impaired liver function, hence it showed that, the subjects with high ALT to be the possible carrier of the HBV. Conversely, the remaining 84.2% (16/19) of the total HBsAg positive subjects were concluded to have the infection either at incubation or at prodrome period. PMID- 11210112 TI - Flavor release of diacetyl and 2-heptanone from cream style dressings in three mouth model systems. AB - The release of volatile compounds from a cream style dressing, which consisted of a thickening agent dispersed in the water phase of an oil in water (o/w) type of emulsion, was studied by the purge-and-trap (PT), dynamic head space mastication (DHM) and dynamic headspace (DH) model systems for diacetyl and 2-heptanone as two volatile compounds. Big differences were detected in the quantity of volatiles released by the three models for both diacetyl and 2-heptanone: PT released the most, followed by DHM and DH. Nitrogen gas bubbling in PT and plunger up-and-down motion in DHM mimic mouth movements and promoted volatile release more than DH. The quantity of volatiles released depended on the nitrogen gas flow rate and isolation period with both the PT and the DHM model. Static headspace measurements indicated that no interaction occurred between the volatiles and the dispersion thickening agent, nor between the volatiles and protein of saliva. PMID- 11210113 TI - Gene cloning and characterization of alpha-glucuronidase of Bacillus stearothermophilus no. 236. AB - The alpha-glucuronidase gene of Bacillus stearothermophilus No. 236 was cloned, sequenced, and expressed in Escherichia coli. The gene, designated aguA, encoded a 691-residue polypeptide with calculated molecular weight of 78,156 and pI of 5.34. The alpha-glucuronidase produced by a recombinant E. coli strain containing the aguA gene was purified to apparent homogeneity and characterized. The molecular weight of the alpha-glucuronidase was 77,000 by SDS-PAGE and 161,000 by gel filtration; the functional form of the alpha-glucuronidase therefore was dimeric. The optimal pH and temperature for the enzyme activity were pH 6.5 and 40 degrees C, respectively. The enzyme's half-life at 50 degrees C was 50 min. The values for the kinetic parameters of Km and Vmax were 0.78 mM and 15.3 U/mg for aldotriouronic acid [2-O-alpha-(4-O-methyl-alpha-D-glucopyranosyluronic)-D xylobiose]. The alpha-glucuronidase acted mainly on small substituted xylo oligomers and did not release methylglucuronic acid from intact xylan. Nevertheless, synergism in the release of xylose from xylan was found when alpha glucuronidase was added to a mixture of endoxylanase and beta-xylosidase. PMID- 11210114 TI - Modulation of cholesterol concentration in Caco-2 cells by incubation with different n-6 fatty acids. AB - Incorporation of exogenous cholesterol was compared in human adenocarcinoma colon cells (Caco-2) after incubation with 100 microM of either linoleic acid (LA, 18:2n-6), gamma-linolenic acid (GLA, 18:3n-6), arachidonic acid (AA, 20:4n-6) or adrenic acid (or n-6 docosatetraenoic acid, DTA, 22:4n-6). In both cells 7 days after seeding and 14 days after confluency, incubation with LA significantly raised the proportion of 18:2n-6 but not its long-chain metabolites in cellular phospholipid. Incubation with GLA increased the levels of 18:3n-6, 20:3n-6, and 20:4n-6. Incubation with AA increased the levels of 20:4n-6 and 22:4n-6, and incubation with DTA increased the levels of 22:4n-6 as well as its retro conversion metabolite, 20:4n-6. A subsequent addition of cholesterol (180 microM) to the medium significantly raised the cellular cholesterol level but less so in the cells 7 days after seeding incubated with GLA. The increase in cellular cholesterol level was generally greater in the cells of 7 days after seeding, particularly those incubated with long-chain highly unsaturated n-6 fatty acids, than in those of 14 days after confluency. These findings suggest that the cell growth and the extent of unsaturation in cell membrane phospholipid fatty acids modulate the incorporation of the exogenous cholesterol into the Caco-2 cells. PMID- 11210115 TI - Plasma cholesterol-lowering effect on rats of dietary fiber extracted from immature plants. AB - Crude dietary fiber samples were prepared from beet, cabbage, Japanese radish, onion and mung bean sprouts (BF, CF, RF, OF and MF, respectively). These samples contained total dietary fiber at the levels of 814, 699, 760, 693 and 666 g/kg, respectively. To examine the effect of these dietary fiber sources on the plasma cholesterol concentration, male Sprague-Dawley rats were fed on a fiber-free (FF) diet or on an FF diet supplemented with 5% or 10% dietary fiber. Dietary fiber extracted from vegetables, wood cellulose (CL), pectin (PE) and guar gum (GG) were used as the fiber sources. Compared with the rats fed on the FF diet, a significant reduction in the plasma cholesterol concentration was observed in the rats fed on BF, CF, RF, MF, PE or GG after a 21-d feeding period. Cecal acetate, n-butyrate and total short-chain fatty acids were significantly higher in the rats fed on these dietary fibers, except for CF, than in those fed on the FF diet. A negative correlation was apparent between the total dietary fiber content, hemicellulose content and pectin content of each dietary fiber source and the plasma cholesterol concentration. These results suggest that some vegetable fibers exert a plasma cholesterol-lowering effect through cecal fermentation of these fibers. PMID- 11210116 TI - Time-dependent structure and activity changes of alpha-chymotrypsin in water/alcohol mixed solvents. AB - Secondary structure of alpha-chymotrypsin in water/ethanol was investigated by circular dichroic (CD) spectroscopy. The changes in catalytic activity were discussed in terms of structural changes of the enzyme. Alpha-chymotrypsin formed beta-sheet structure in water/ethanol (50/50 by volume), but it was substantially less active as compared to that in water. At water/ethanol 10/90, alpha chymotrypsin took on a native-like structure, which gradually changed to beta conformation with concomitant loss of activity. Change of solvent composition from water/ethanol 50/50 to 90/10 or 10/90 by dilution with water or ethanol, respectively, led to partial recovery of native or native-like structure and activity. In water/methanol, alpha-chymotrypsin tended to form stable beta-sheet structure at water/methanol ratios lower than 50/50, but the catalytic activity decreased with time. Change to alpha-helix structure with substantial loss in catalytic activity was observed when alpha-chymotrypsin was dissolved in water/2,2,2-trifluoroethanol with water contents lower than 50%. In water/2,2,2 trifluoroethanol 90/10, alpha-chymotrypsin initially had the CD spectrum of native structure, but it changed with time to that characteristic of beta-sheet structure. PMID- 11210117 TI - Nematicidal alkaloids and related compounds produced by the fungus Penicillium cf. simplicissimum. AB - A new nematicidal alkaloid, peniprequinolone (1), together with the known alkaloids penigequinolones A and B (2a, 2b), 3-methoxy-4-hydroxy-4-(4' methoxyphenyl)quinolinone (3), and 3-methoxy-4,6-dihydroxy-4-(4' methoxyphenyl)quinolinone (4), were isolated from Penicillium cf. simplicissimum (Oudemans) Thom. Cyclopenin (5) and a compound (6a/6b) structurally related to cyclopenin also were isolated from the fungus, and their structures were established by spectroscopic analysis. The biological activities of 1, 2, 3, 4, and 5 were examined by a bioassay with root-lesion nematodes. PMID- 11210118 TI - New anthocyanins from purple pods of pea (Pisum spp.). AB - Two new anthocyanins were isolated from purple pods of pea (Pisum spp.). Their structures were identified as delphinidin 3-xylosylgalactoside-5-acetylglucoside and its deacetylated derivative by the usual chemical degradation methods and by spectroscopic methods such as UV-VIS, MS and NMR. Both pigments showed moderate stability and antioxidative activity in a neutral aqueous solution. PMID- 11210119 TI - DNA repair effect of traditional sweet pepper Fushimi-togarashi: seen in suppression of UV-induced cyclobutane pyrimidine dimer in human fibroblast. AB - The aqueous fraction of Fushimi sweet pepper increased the repair effect of the solvent control against UV-induced cyclobutane pyrimidine dimers in human fibroblast to 150%, but ordinary sweet pepper did not have a statistically significant effect. When Fushimi sweet pepper was boiled, the activity of the aqueous fraction was elevated to 209% of the control (p<0.05), while that of the grilled state was decreased to 125% of the control. The repair activity of a dialyzate (MW<12,000) of the aqueous fraction from Fushimi sweet pepper showed 191% of the control (p<0.05). The dialyzate was contained 1.9% in the weight of the fresh fruit body of Fushimi sweet pepper, and the activity can be stable in its boiling state, and it might be therefore considered to be the worthy source for expecting the DNA repair activity in human diet. PMID- 11210120 TI - Analyses of polyphenols in cacao liquor, cocoa, and chocolate by normal-phase and reversed-phase HPLC. AB - The antioxidant polyphenols in cacao liquor, a major ingredient of chocolate and cocoa, have been characterized as flavan-3-ols and proanthocyanidin oligomers. In this study, various cacao products were analyzed by normal-phase HPLC, and the profiles and quantities of the polyphenols present, grouped by molecular size (monomers to approximately oligomers), were compared. Individual cacao polyphenols, flavan-3-ols (catechin and epicatechin), and dimeric (procyanidin B2), trimeric (procyanidin C1), and tetrameric (cinnamtannin A2) proanthocyanidins, and galactopyranosyl-ent-(-)-epicatechin (2alpha-->7, 4alpha- >8)-(-)-epicatechin (Gal-EC-EC), were analyzed by reversed-phase HPLC and/or HPLC/MS. The profile of monomers (catechins) and proanthocyanidin in dark chocolate was similar to that of cacao liquor, while the ratio of flavan-3-ols to the total amount of monomeric and oligomeric polyphenols in the case of pure cocoa powder was higher than that in the case of cacao liquor or chocolate. PMID- 11210121 TI - Dietary effects of eicosapentaenoic and docosahexaenoic acid esters on lipid metabolism and immune parameters in Sprague-Dawley rats. AB - Sprague-Dawley rats were fed eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) ethyl esters at the 2% level for 3 weeks to clarify their effects on immune functions. In the rats fed EPA or DHA, serum cholesterol, triglyceride, and phospholipid (PL) levels were significantly lower than those in the rats fed safflower oil. In PL fractions of serum, liver, lung, splenocytes, and peritoneal exudate cells (PEC), increases in linoleic and dihomo-gamma-linolenic acid contents and a decrease in arachidonic acid (AA) content were observed in the rats fed EPA or DHA. In addition, the EPA content increased in the rats fed EPA and DHA. In the rats fed EPA or DHA, a decrease of LTB4 productivity and an increase of LTBs productivity were observed in the PEC, in response to the treatment with 5 microM calcium ionophore A23187 for 20 min. The changes in leukotriene production were more marked in EPA-fed rats than in DHA-fed rats. These results suggest that dietary EPA affects lipid metabolism and leukotriene synthesis more strongly than DHA. PMID- 11210122 TI - Effect of soy and milk whey protein isolates and their hydrolysates on weight reduction in genetically obese mice. AB - The effect on genetically obese mice of a milk whey protein isolate (WPI) and soy protein isolate (SPI) and their hydrolysates (WPI-H, SPI-H) on the rate of body fat disappearance was investigated. Male yellow KK mice were made obese by feeding with a high-fat diet containing 30% fat from 6 to 10 weeks of age. They were then fed with an energy-restricted low fat (5.0%) and high protein (35% WPI, WPI-H, SPI or SPI-H) diet for 2 weeks at the 60% level of energy intake by mice on laboratory feed. During the weight reduction period, the body weight of the WPI, WPI-H, SPI and SPI-H groups changed by -9.1, -9.1, -10.0 and -11.1 g/14 days, respectively, the reduction being significantly lower in the SPI-H group than in the WPI and WPI-H groups. The plasma total cholesterol level was significantly lower with the SPI diet, and the plasma glucose level was lower with the SPI and SPI-H diets than with the WPI and WPI-H diets. Although the body protein content was comparable in all the groups, the body fat content was significantly lower with the SPI diet than with the WPI diet, and was also significantly lower with the SPI-H diet than with the WPI and WPI-H diets. The weight of the perirenal fat pads was significantly lower with the SPI-H diet than with the WPI and WPI-H diets. These results indicate that SPI and SPI-H are suitable protein sources in an energy-restricted diet for treating obesity. PMID- 11210124 TI - Comparison of substrate specificities of transglutaminases using synthetic peptides as acyl donors. AB - Transglutaminase (TGase) is an enzyme that catalyzes acyl transfer reactions between primary amines and Gln residues in proteins or peptides. Substrate specificities of TGase, Ca2+-independent microbial transglutaminase (MTGase), and Ca2+-dependent tissue type transglutaminase from guinea pig liver (GTGase) and fish, Red sea bream (Pagrus major), liver (FTGase), for acyl donors were investigated using synthetic peptides containing Gln residues and Gln analogues with different lengths of side chain. MTGase dose not recognize the Gln analogues as a substrate and has strict substrate specificities toward L-Gln. Substrate peptides with a variety of sequences around the Gln residue, GXXQXXG (X=G, A, S, L, V, F, Y, R, N, E, L) were synthesized and used as acyl donors. As an acyl acceptor, the fluorescent reagent monodancyl cadaverine was used and the reactions analyzed with RP-HPLC. Substitution of the C-terminal of a Gln residue with a hydrophobic amino acid accelerated the reaction by GTGase and FTGase. N terminal substitution of Gln residues had similar effects on the reaction by MTGase. PMID- 11210123 TI - Splice isoforms of transcription factor Elf-1 affecting its regulatory function in transcription-molecular cloning of rat Elf-1. AB - To elucidate the role of Elf-1 in Fc epsilonRI alpha chain expression, rat Elf-1 cDNAs were isolated and characterized. The rat Elf-1 cDNA of 2744 bp contained an open reading frame of 1848 bp. In addition to the full length rat Elf-1 cDNA (named type 1), two splice isoforms were isolated. One of the two isoforms lacked the amino acid residues from 85th to 120th (type 2), and the other from 85th to 175th (type 3). Similar isoforms were also observed in human tissue. Overexpression of rat Elf-1 (type 1) using a transient coexpression system inhibited of the alpha chain promoter activity. The inhibition activity was different between the isoforms; the inhibition activity of type 2 was lower than that of type 1, and type 3 did not have an inhibitory effect. This observation suggested that each Elf-1 isoform played a different role in the gene expression under its control. PMID- 11210125 TI - Cloning, sequencing, and expression of the gene encoding a cell-bound multi domain xylanase from Clostridium josui, and characterization of the translated product. AB - The nucleotide sequence of the Clostridium josui FERM P-9684 xyn10A gene, encoding a xylanase Xyn10A, consists of 3,150 bp and encodes 1,050 amino acids with a molecular weight of 115,564. Xyn10A is a multidomain enzyme composed of an N-terminal signal peptide and six domains in the following order: two thermostabilizing domains, a family 10 xylanase domain, a family 9 carbohydrate binding module (CBM), and two S-layer homologous (SLH) domains. Immunological analysis indicated the presence of Xyn10A in the culture supernatant of C. josui FERM P-9684 and on the cell surface. The full-length Xyn10A expressed in a recombinant Escherichia coli strain bound to ball-milled cellulose (BMC) and the cell wall fragments of C. josui, indicating that both the CBM and the SLH domains are fully functional in the recombinant enzyme. An 85-kDa xylanase species derived from Xyn10A by partial proteolysis at the C-terminal side, most likely at the internal region of the CBM, retained the ability to bind to BMC. This observation suggests that the catalytic domain or the thermostabilizing domains are responsible for binding of the enzyme to BMC. Xyn10A-II, the 100-kDa derivative of Xyn10A, was purified from the recombinant E. coli strain and characterized. The enzyme was highly active toward xylan but not toward p nitrophenyl-beta-D-xylopyranoside, p-nitrophenyl-beta-D-cellobioside, or carboxymethylcellulose. PMID- 11210126 TI - Biogenic amines in Drosophila virilis under stress conditions. AB - The effect of heat stress (38 degrees C) on the content of DL-beta-(3,4 dihydroxyphenyl)alanine (DOPA), dopamine, tyramine, octopamine, and their precursor Tyr was studied in adults of two lines of Drosophila virilis contrasting in their stress response. In individuals of line 101 responding to stress by a hormonal stress reaction, the contents of DOPA, dopamine, octopamine, and Tyr were lower than those of line 147 that did not respond to the stress. However, heat stress caused an increase in the contents of DOPA, dopamine, octopamine, and Tyr in line 101, whereas the equivalent titers in line 147 remain unchanged. PMID- 11210127 TI - Prophage, phiPV83-pro, carrying panton-valentine leukocidin genes, on the Staphylococcus aureus P83 chromosome: comparative analysis of the genome structures of phiPV83-pro, phiPVL, phi11, and other phages. AB - Staphylococcus aureus P83 has Panton-Valentine leukocidin (PVL)-like genes, lukM and lukF-PV. Here, lukM and lukF-PV genes were found on the genome of a prophage, which was designated as phiPV83-pro. The precise genome size was 45,636 bp with att core sequences of 10 base pairs. Sixty-four ORFs were identified on the phiPV83-pro genome, including two extra operons, lukM-lukF-PV and orfs63-64. The lukM-lukF-PV cluster was located 2.1 kb upstream of the attL site. The most striking feature of the phiPV83-pro genome was a constituent of at least 4 regions from phi11, phiPVL, and other phages, i.e., (i) att sites identical with those of phi11, (ii) a cos sequence and the genes encoding packaging and head proteins of phiPVL (occupied half region of phiPV83-pro), and (iii) the other two regions which showed no significant similarity with known phages (occupied about 40% of phiPV83-pro). Furthermore, two insertion sequences, ISSA1 and ISSA2 were integrated into attL site and orf44, respectively. PhiPV83-pro was not induced as phage particles from S. aureus P83 regardless of its treatment with mitomycin C. The insertion of ISSA1 into the attL site was one of the reasons of the failure of the induction of the phage particles by mitomycin C treatment of the strain P83. PMID- 11210128 TI - Metabolism of chiral ionylideneacetic acids on the abscisic acid biosynthetic pathway in Cercospora. AB - A Chiralcel OJ column was used to determine the absolute configuration of naturally occurring alpha-ionylideneacetic acid from Cercospora rosicola and gamma-ionylideneacetic acid from C. cruenta as (R) enantiomers in accordance with their biosynthetic product, (S)-ABA. Both enantiomers of [1, 2-(13)C2]-alpha and gamma-ionylideneacetic acids were prepared and fed to C. rosicola and C. cruenta. Six combinations of feeding experiments comparatively and unequivocally demonstrated stereoselectivity in the biosynthetic conversions, including stepwise hydroxylation at C-1' and 4'. Enzymatic isomerization from the gamma to alpha-intermediate was suggested not to be involved in ABA biosynthesis in C. rosicola. PMID- 11210129 TI - Identification of a compound in Chamaecyparis taiwanensis inhibiting the ice nucleating activity of Pseudomonas fluorescens KUIN-1. AB - Inactivation of the ice-nucleating activity of Pseudomonas fluorescens KUIN-1 by compounds in the leaves from coniferous trees were investigated, and the inactivated material was identified. Intact cells of the strain KUIN-1 and the acetone or methanol extracts of leaves of various coniferous trees were allowed to react for 30 min at 18 degrees C. Antinucleation compounds were obtained from Chamaecyparis taiwanensis. When the acetone extract from the leaves of coniferous trees was added to the cell suspension (about 10(6) cells/ml) in 50 mM potassium phosphate buffer (pH 7.0), the ice nucleating temperature, T50, was significantly decreased (T50 < -5 degrees C). This inhibitor was isolated by using TLC, then identified as hinokitiol based on UV-VIS, IR, and mass spectral data. When intact cells of the strain KUIN-1 were incubated with hinokitiol, limonene, and alpha pinene of the principal constituent of the leaves of coniferous trees in 50 mM potassium phosphate buffer (pH 7.0), the ice-nucleating activity decreased, but not in alpha-terpinene. Furthermore, the ice-nucleating activities from other ice nucleating bacteria also decreased in the presence of hinokitiol. This inhibition was proportional to the concentration of hinokitinol. The pH and thermal stabilities of the ice-nucleating activity of the cells were changed by the addition of hinokitiol (10 mM). PMID- 11210130 TI - Ecdysteroids in stress responsive and nonresponsive Drosophila virilis lines under stress conditions. AB - After exposure to thermal stress or a control temperature, the relative abundance of ecdysone (E) and 20-hydroxyecdysone (20E) was measured in a wild-type line of Drosophila virilis (101) that is stress responsive and in a mutant line (147) that is not stress responsive. In line 101, the 20E content was higher and E content lower in females than in males. The abundance of E and 20E in females of line 147 was significantly higher than that in females of line 101. Females of line 101 were found to respond to 60 min of heat stress (38 degrees C) by an increase in the abundance of both E and 20E, while in males of this line the amount of 20E increased and that of E declined. A role of the ecdysteroids in the control of reproduction of D. virilis under stress is discussed. PMID- 11210131 TI - Novel method for producing hypoallergenic wheat flour by enzymatic fragmentation of the constituent allergens and its application to food processing. AB - A novel method is proposed to produce hypoallergenic wheat flour suitable for patients allergic to wheat. Wheat flour was mixed with a cellulase solution, and the mixture was incubated at 50 degrees C for 1 h to hydrolyze the carbohydrate allergens. The hydrolysate was further incubated with actinase at 40 degrees C for 1 h while gently stirring to decompose the proteinaceous allergens. The product was evaluated for its allergenicity by an enzyme-linked immunosorbent assay, the results of which suggested negative allergenicity in most cases. The product changed to a batter state that was difficult to process by the usual methods. Gelatinization of the starch in the product and the addition of a surfactant were beneficial for food processing. PMID- 11210132 TI - A cold acclimation protein with refolding activity on frozen denatured enzymes. AB - We found that a cold acclimation protein from an ice-nucleating bacterium, Patoea ananas KUIN-3, has refolding activity on frozen denatured protein. Based on a SDS PAGE analysis, we confirmed that the cold shock-treated cells of strain KUIN-3 could produce some cold acclimation proteins that inhibit their syntheses by the addition of chloramphenicol during the cold acclimation. Among such proteins, Hsc25 had refolding activity similar to GroELS. Hsc25 was purified to apparent homogeneity by (NH4)2SO4 precipitation and some chromatographies. The purified Hsc25 was composed of 8 subunits of 25,000 each with a molecular mass of 200,000 and had refolding activity against denatured enzymes, which were denatured by heat-treatment at 100 degrees C, cryopreservation at -20 degrees C, or guanidine hydrochloride, in a manner similar to GroELS. The N-terminal sequence of Hsc25 was Met-Arg-Ala-Ser-Thr-Tyr-His-Ala-Ala-Arg-. Furthermore, Hsc25 had a high level of activity at low temperature (12 degrees C). Also, the dissociation constants, KD (M) as the binding specificity for enolase, mutarotase, isocitrate dehydrogenase, and lactate dehydrogenase were 1.82x10(-10), 4.35x10(-9), 8.98x10( 12), and 3.05x10(-11), respectively. The affinity of Hsc25 for frozen danatured enzymes was higher than the affinity for heat denatured enzymes when compared with the affinity of GroEL. These results are the first report on the characterization of a purified chaperon that was induced by cold acclimation. PMID- 11210133 TI - Efflux system for pyridoxine in Schizosaccharomyces pombe. AB - Pyridoxine-charged Schizosaccharomyces pombe released pyridoxine rapidly at 30 degrees C: very low amounts of three other B6 vitamers were also released. The rate of efflux was temperature-dependent. The initial rate of efflux was dependent on the concentration of pyridoxine in the cells: the rate was almost zero at lower than 0.02 mM and became saturated at higher than 0.2 mM. Na+, sodium azide, and dinitrophenol increased the rate in both the presence and absence of D-glucose. Mg++, thiamine, and menadione inhibited the efflux. The intracellular concentration of ATP did not significantly affect the efflux rate. The system may be dependent on a membrane potential of the yeast cells. It was found that the fission yeast cells have a gate or carrier system for efflux of pyridoxine, which was distinct from that in Saccharomyces cerevisiae. PMID- 11210134 TI - Alpha-oxidation of long-chain unsaturated fatty acids in the marine green alga Ulva pertusa. AB - When long-chain unsaturated fatty acids such as oleic, linoleic, and linolenic acid were incubated with crude enzymes from the marine green alga Ulva pertusa, the corresponding (R)-2-hydroperoxy acids were formed with a high enantiomeric excess (>99%). PMID- 11210135 TI - cDNA cloning of the Cry1Aa receptor variants from Bombyx mori and their expression in mammalian cells. AB - We cloned cDNA of three variants of BtR175, a putative Bombyx mori receptor for Bacillus thuringiensis Cry1Aa delta-endotoxin by PCR. These variants were likely to be allelic to BtR175. cDNA of BtR175b, the most distant variant from BtR175, was introduced into mammalian cells. BtR175b protein was expressed in the plasma membrane of the cells and showed binding activity to Cry1Aa. PMID- 11210136 TI - Effects of corticosterone on connectin content and protein breakdown in rat skeletal muscle. AB - We examined the effects of a glucocorticoid, corticosterone, on calpain activity, connectin content and protein breakdown in rat muscle. The results indicated that calpain activity was increased by corticosterone and thus breakdown of connectin was stimulated followed by increased breakdown of skeletal muscle protein. PMID- 11210137 TI - Stability and bioavailability of antioxidants in garland (Chrysanthemum coronarium L.). AB - The stability and bioavailability of the major antioxidants in garland (Chrysanthemum coronarium L.), chlorogenic acid, 3,5-dicaffeoylquinic acid and 4 succinyl-3,5-dicaffeoylquinic acid, were investigated together with caffeic acid. These compounds were stable in artificial digestive juice, but more than 90% of them disappeared from plasma within 30 min after intravenous injection into rats. When they were orally administered, only caffeic acid could be detected. PMID- 11210138 TI - Analysis of catalytic residues of Thermoactinomyces vulgaris R-47 alpha-amylase II (TVA II) by site-directed mutagenesis. AB - To confirm that the catalytic residues (Asp325, Glu354, and Asp421) are necessary for the hydrolysis of starch, pullulan, and cyclodextrins, we constructed TVA II mutated by site-directed mutagenesis. The mutated enzymes (D325N, E354Q, and D421N) had markedly reduced levels of activity, less than 0.006% of the wild type, indicating that these three residues are the catalytic sites for these substrates. Even E354D had reduced levels of activity, less than 0.05% of wild type. These four mutated enzymes retained a trace of activity. From the result of hydrolysis patterns for maltohexaose, in particular, D421N, unlike D325N and E354Q, catalyzed transglycosylation rather than hydrolysis. The results suggest that Asp421 could function to capture water molecules. PMID- 11210139 TI - Purification and characterization of cyclohexanone 1,2-monooxygenase from Exophiala jeanselmei strain KUFI-6N. AB - Baeyer-Villiger cyclohexanone 1,2-monooxygenase (CHMO) was purified 17.1-fold from cell extracts of the fungus Exophiala jeanselmei grown on cyclohexanol to electrophoretically homogeneity by serial chromatographies. The molecular mass of the native enzyme was approximately 74 kDa by gel filtration and SDS-PAGE. Some enzymic characterizations were studied. The NH2-terminal amino acid residues were Ala-Lys-Ser-Leu-Asp-Val-Leu-Ile-Val-Gly-Ala-Gly-Phe-Gly-Gly-Ile-Tyr-Gln-Leu-, with similarity to the bacterial CHMOs of FAD-binding and NADPH-dependent type Baeyer-Villiger monooxygenases. PMID- 11210140 TI - Polygodial, a potent attachment-inhibiting substance for the blue mussel, Mytilus edulis galloprovincialis from Tasmannia lanceolata. AB - A highly potent attachment-inhibitor, polygodial, was isolated from a hexane extract of the leaves of Tasmannia lanceolata. The attachment-inhibiting activity of polygodial against the blue mussel was increased 4-fold when used in combination with sorbic acid, anethole, and indole. PMID- 11210141 TI - Synthesis and potato cell expansion-inducing activity of the stereochemically restricted bicyclic analogue of 7-epi-jasmonic acid. AB - The stereochemically restricted bicyclic analogue of 7-epi-jasmonic acid was synthesized from a known bicyclo[3.3.0]octane derivative. The enol triflate derived from the bicyclic compound was subjected to palladium-catalyzed coupling with allyltributyltin to give the desired carbon skeleton. Selective catalytic hydrogenation and subsequent acidic hydrolysis gave a new bicyclic analogue of 7 epi-jasmonic acid. The ACC conjugate of the bicyclic analogue was also synthesized. This ACC conjugate exhibited only slightly weaker potato cell expansion-inducing activity than that of the JA standard. PMID- 11210142 TI - Effects of a fermented milk drink containing Lactobacillus casei strain Shirota on the immune system in healthy human subjects. AB - Nine healthy volunteers drank fermented milk containing 4 x 10(10) live cells of Lactobacillus casei strain Shirota daily for 3 weeks, and their NK activity and other immunological functions were measured. NK activity significantly increased (p<0.01) 3 weeks after the start of intake and remained elevated for the next 3 weeks. The effect was particularly prominent in low-NK-individuals. PMID- 11210143 TI - Microbial degradation of disodium terephthalate by alkaliphilic Dietzia sp. strain GS-1. AB - An alkaliphilic Dietzia sp., strain GS-1, which degraded disodium terephthalate (DT), was isolated from soil. Strain GS-1 degraded 19.3 mM of DT in 168 h at pH 10. The maximum degradation velocity was 0.46 mM/h. The resting cells efficiently degraded 28.7 mM of DT in 51 h at 28 degrees C and pH 10. The degradation velocity was 0.41 mM/(h g-wet cell). PMID- 11210144 TI - Characterization of a vitamin B12 compound in the edible purple laver, Porphyra yezoensis. AB - The edible purple laver, Porphyra yezoensis, contained 51.49+/-1.51 microg of vitamin B12 compounds per 100 g dry weight of the laver (mean +/- SEM, n = 4). A vitamin B12 compound was purified from the lyophilized purple laver and partially characterized. The silica gel 60 TLC and reversed-phase HPLC patterns of the purified pink-colored compound were identical to those of authentic vitamin B12, but not to those of vitamin B12 analogues inactive for humans. PMID- 11210145 TI - Secretion of hen egg white lysozyme from Kluyveromyces lactis. AB - Hen egg white (HEW) lysozyme was correctly processed and efficiently secreted from an alternative yeast, Kluyveromyces lactis. We constructed secretion vectors using PHO5, PGK, and LAC4 promoters, and found that the highest secretion was obtained under the direction of the PGK promoter in non-selective rich medium. K. lactis secreted HEW lysozyme with two-fold higher efficiency than S. cerevisiae, estimated by using a K. lactis-S. cerevisiae shuttle vector. PMID- 11210146 TI - Specific toxic effect of dinoflagellate Heterocapsa circularisquama on the rotifer Brachionus plicatilis. AB - Heterocapsa circularisquama (Dinophyceae), a noxious red tide dinoflagellate, is known to have a specifically lethal effect on shellfish, especially bivalves such as pearl oyster (Pinctada fucata), but no detrimental effects of this alga on fishes have not been observed so far. In this study, we found that H. circularisquama was toxic to a microzooplankton, a rotifer (Brachionus plicatilis) in a cell concentration-dependent manner, while the cultured supernatant or ultrasonic ruptured H. circularisquama had no significant toxic effect on the rotifer. Since no such toxic effects on the rotifer were observed in Chattonella marina, Heterosigma akashiwo, or Cochlodinium polykrikoides, other species of harmful red tide plankton, H. circularisquama may have a strictly specific toxic mechanism against the rotifer as well as bivalves. PMID- 11210147 TI - Synthesis of all four possible stereoisomers of 5,9-dimethylpentadecane, the major sex pheromone component of the coffee leaf miner moth, Perileucoptera coffeella. AB - All of the four possible stereoisomers of 5,9-dimethylpentadecane, the major sex pheromone component of the coffee leaf miner moth (Perileucoptera coffeella), were synthesized by using the methyl esters of (S)- and (R)-3-hydroxy-2 methylpropanoic acid as chiral sources for the purpose of determining the stereochemistry of the pheromone. PMID- 11210148 TI - Purification and characterization of nitrite-oxidizing enzyme from heterotrophic Bacillus badius 1-73, with special concern to catalase. AB - Nitrite-oxidizing enzyme I (NiOx I) was purified from a heterotrophic bacterium, Bacillus badius I-73. The enzyme was a homotetramer of a heme-containing peptide, and was similar to catalases from various sources in its N-terminal amino acid sequence. The purified enzyme also catalyzed H2O2 degradation. The nitrite oxidation reaction required ascorbic acid and oxygen. Successive H2O2 feeding could be substituted for ascorbic acid. These indicated that NiOx I is a catalase and nitrite was oxidized by a peroxidase-like reaction. PMID- 11210149 TI - Introduction of enterostatin (VPDPR) and a related sequence into soybean proglycinin A1aB1b subunit by site-directed mutagenesis. AB - Enterostatin (VPDPR), having anoretic and hypocholesterolemic activities, and its homologue LPYPR, a hypocholesterolemic peptide found in the glycinin A5A4B3 subunit, were introduced into the corresponding site (TNGPQ) of the proglycinin A1aB1b subunit by site-directed mutagenesis. Modified proglycinins were expressed in E. coli and recovered from the insoluble fraction. VPDPR and LPYPR were released by the action of chymotrypsin and trypsin as expected. The overall yields of purified VPDPR and LPYPR were 40% and 62%, respectively. PMID- 11210150 TI - Molecular cloning, overexpression, and purification of a major xylanase from Aspergillus oryzae. AB - The gene encoding xylanase G2 (xynG2) was isolated from a genomic library of Aspergillus oryzae KBN616, used for making shoyu koji. The structural part of xynG2 was found to be 767 bp. The nucleotide sequence of cDNA amplified by RT-PCR showed that the open reading frame of xynG2 was interrupted by a single intron which was 71 bp in size and encoded 232 amino acids. Direct N-terminal amino acid sequencing showed that the precursor of XynG2 had a signal peptide of 44 amino acids. The predicted amino acid sequence of XynG2 has strong similarity to other family 11 xylanases from fungi. The xynG2 gene was successfully overexpressed in A. oryzae and the overpexpressed XynG2 was purified. The molecular weight of XynG2 estimated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis was 21,000. This was almost the same as the molecular weight of 20,047 calculated from the deduced amino acid sequence. The purified XynG2 showed an optimum activity at pH 6.0 and 58 degrees C. It had a Km of 5.1 mg/ml and a Vmax of 123 micromol/min/mg when birch wood xylan was used as a substrate. PMID- 11210151 TI - Enzymatic preparation of genuine prosapogenin, 20(S)-ginsenoside Rh1, from ginsenosides Re and Rg1. AB - It was found that a lactase preparation from Penicillium sp. nearly quantitatively hydrolyzed ginsenosides Re and Rg1, which are major saponins in roots of Panax ginseng, to a minor saponin, 20(S)-ginsenoside Rh1 [6-O-beta-D glucopyranosyl-20(S)-protopanaxatriol]. This is the first report on the enzymatic preparation of ginsenoside Rh1 with a high efficiency. This enzyme also readily hydrolyzed ginsenoside Rg2 to ginsenoside Rh1. PMID- 11210152 TI - Tyrosine72 residue at the bottom of rim domain in LukF crucial for the sequential binding of the staphylococcal gamma-hemolysin to human erythrocytes. AB - Staphylococcal bi-component cytotoxins, leukocidin (Luk), Panton-Valentine leukocidin (PVL), and gamma-hemolysin (Hlg) consist of LukF and LukS, LukF-PV and LukS-PV, and LukF and Hlg2, respectively, and Luk and Hlg share LukF. LukF-PV can not substitute for LukF for Hlg, despite 73% identity in amino acid sequence and close similarity in the 3-dimensional structure between them. Here, we demonstrated that the absence of hemolytic activity of LukF-PV in cooperation with Hlg2 is due to the failure of the binding of LukF-PV to human erythrocytes. We identified Y72 residue at the bottom of rim domain in LukF as the crucial residue for its binding, which is a prerequisite to the subsequent binding of Hlg2 to human erythrocytes. The data obtained showed that a mutant of LukF-PV in which T71 residue was replaced by the corresponding residue of LukF, Y72, endowed LukF-PV with the binding capability to human erythrocytes which was accompanied by its hemolytic activity in the presence of Hlg2. PMID- 11210153 TI - Haemolytic index and performance of a magnetically coupled rotary pulsatile pump with potential for ventricular assist. AB - A novel magnetically coupled rotary vane pump is described which has the potential to be used as a ventricular assist device. The pump has an excellent haemodynamic performance. When tested, pumping blood, against a range of pressures from 20 to 100 mm Hg the volumetric output varied within reasonable limits. The pump could deliver 5.1 litres per minute against a pressure of 180 mm Hg before the magnetic coupling disengaged. With specially moulded magnets improved coupling can be achieved. The haemolytic index was determined using a circuit conforming to ASTM: F04-40-101. The NIH (normalised index of haemolysis) was found to be 0.3 and the MIH (modified index of haemolysis) 0.26 which is unacceptably high for long term perfusion. The pump has several outstanding features, it is hermetically sealed, it needs no valving, a desirable property in a ventricular assist pump, and it has a pulsatile action. In a non magnetically coupled form it performed satisfactorily in left ventricular assist mode and as a total cardiopulmonary bypass pump in short term experiments with dogs. PMID- 11210154 TI - Plasma sample preparation by ultrafiltration for FTIR analysis. AB - Total body water (TBW) may be significantly altered with disease. Isotope dilution techniques, considered to be the "gold standard" methods for measuring TBW, are expensive, time consuming and require considerable expertise, especially during the sample preparatory phase. In this study, a new method, ultrafiltration (UF), was hypothesised to be an efficient alternative to vacuum sublimation (VS) in the preparation of plasma samples for Fourier Transform Infra Red (FTIR) determination of TBW. Deuterium Oxide (D2O) concentrations were prepared in human plasma and subjected to both techniques. FTIR analysis was carried out on the resulting VS and UF solutions and on D2O concentrations in distilled water. The resulting absorbance values were then statistically compared. Urea concentrations prepared in D2O-containing plasma were also compared to "blank" plasma to investigate the effect of high plasma urea concentration on the resulting H2O/D2O mixture obtained during UF Paired t-tests showed that the VS plasma samples (p=0.003), but not the UF samples (p=0.9), were significantly different to D2O standards prepared in distilled water. While there was no evidence of an effect of urea on UF at low (0.4 g/L) D2O concentration, a marginal (p=0.04) effect occurred at a higher (1.6 g/L) D2O level. Throughput of samples was much more efficient with the UF technique. These findings indicate that the new UF method is an accurate, more efficient method of plasma sample preparation than the VS method in the FTIR determination of TBW. PMID- 11210155 TI - Three-dimensional clinical measurement of bilateral hip and knee rotations. AB - This paper reports a technique of using an electromagnetic system to measure three-dimensional bilateral hip and knee joint rotations during walking and of using peak cross-correlation between rotation angles to describe the pattern of rotations. Three-dimensional rotations of thigh and shank during gait were recorded using five receivers of the electromagnetic system synchronised with four foot-switches. Thirteen normal subjects were tested on two separate occasions to examine repeatability of the measurements. The relationship between the rotations was represented as lags at peak cross-correlation. Twelve parameters of the lags at peak cross-correlation were calculated. The analysis showed that the joint rotation could be measured reliably and the cross correlation analysis provided parameters that were generally suitable for defining characteristics of hip and knee joint rotations during gait. PMID- 11210156 TI - Evaluation of a second set of lateral lasers for easier patient positioning in radiotherapy. AB - On modern linear accelerators patient set-up is often awkward due to the height of the isocentre. A second set of lateral lasers was mounted approximately 20 cm below the isocentre allowing patient positioning at an ergonomical height. A small randomised study involving 16 heavy patients treated for pelvic malignancies demonstrated that using the lower lasers for patient set-up is not only likely to reduce strain on staff but also speed up the set-up process. PMID- 11210157 TI - Evaluation of the mechanical alignment of a linear accelerator with an electronic portal imaging device (EPID). AB - Mechanical misalignment of a medical linear accelerator can be caused by any combination of source position displacement relative to the collimator rotational axis, collimator jaw asymmetry, or when the rotational axes of the gantry and the collimator do not intersect. A test procedure sensitive to all of these problems has been developed using an Electronic Portal Imaging Device (EPID). Each marker is placed on top of the EPID housing and on the treatment couch, then two images are acquired for gantry positions 180 degrees apart. By comparing the positions of the markers and their distances to the beam centre, mechanical alignment of the linear accelerator can be assessed. By comparing the positions of the beam centre for another two images acquired at collimator angles 180 degrees apart, the three potential sources of misalignment can be distinguished. Results with Siemens' Beam View were presented and determination accuracy of better than 0.25 mm can be achieved. PMID- 11210158 TI - A quality assurance index for brachytherapy treatment plan verification. AB - A method is described which provides an independent verification of a brachytherapy treatment plan. The method is applicable to any common geometric configuration and utilises a simple equation derived from a common form of non linear regression. The basis for the index value is the relationship between the treatment time, prescribed dose, source strength and plan geometry. This relationship may be described mathematically as: Total Treatment Time proportional to (Prescribed Dose/Source Strength) x (a geometric term) with the geometric term incorporating three geometric components, namely the distance from source positions to points of dose normalisation d, the total length of the dwell positions L, and the number of source trains or catheters N. A general equation of the form GF = k (d)(-alpha) (L)(-beta) (N)(-gamma) is used to describe the plan geometry, where GF is what we have termed the geometric factor, k is a constant of proportionality and the exponents are derived from the non-linear regression process. The resulting index is simple to calculate prior to patient treatment and sensitive enough to identify significant error whilst being robust enough to allow for a normal degree of geometric distortion. PMID- 11210159 TI - Monte Carlo calculation for microplanar beam radiography. AB - In radiography the scattered radiation from the off-target region decreases the contrast of the target image. We propose that a bundle of collimated, closely spaced, microplanar beams can reduce the scattered radiation and eliminate the effect of secondary electron dose, thus increasing the image dose contrast in the detector. The lateral and depth dose distributions of 20-200 keV microplanar beams are investigated using the EGS4 Monte Carlo code to calculate the depth doses and dose profiles in a 6 cm x 6 cm x 6 cm tissue phantom. The maximum dose on the primary beam axis (peak) and the minimum inter-beam scattered dose (valley) are compared at different photon energies and the optimum energy range for microbeam radiography is found. Results show that a bundle of closely spaced microplanar beams can give superior contrast imaging to a single macrobeam of the same overall area. PMID- 11210160 TI - Biomathematical modelling of physiological fluids using a Casson fluid with emphasis to peristalsis. AB - In this paper, the peristaltic flow of rheologically complex physiological fluids when modelled by a non-Newtonian Casson fluid in a two-dimensional channel is considered. Of interest is the difference between peristaltic transport of Newtonian and non-Newtonian fluids. A perturbation series method of solution of the stream function in amplitude ratio is sought. It is found that Newtonian fluid is an important sub-class of non-Newtonian fluids that may adequately represent some physiological phenomena. It is shown that for a Casson fluid, when certain simplifications and approximations are made in the most generalised form of constitutive equation, the fluid may be adequately represented as an improvement of a Newtonian fluid. PMID- 11210161 TI - The temporal organization of life: the impact of multi-frequency non-linear biologic time structure upon the host-cancer balance. AB - The current scientific paradigm, based upon an erroneous assumption of linear biologic reality and simple cause and effect relationships, has outlived its usefulness. In order to begin to turn the voluminous data the reductive process provides us with daily into meaningful understanding of life, it is essential to integrate these data within a complex, multi-frequency temporo-spatial framework. This rhythmic chronobiology more accurately depicts the life process, as well as its evolutionary and ongoing vital interaction with the pulsating cosmic resonance structure. Examples of the kinds of thinking and experiments necessary to exploit this new paradigm are provided. PMID- 11210162 TI - Prognostic factors in advanced non-small cell lung cancer: elevated serum levels of neuron specific enolase indicate poor prognosis. AB - BACKGROUND: Non-small cell lung cancer (NSCLC) is resistant to chemotherapy and prognosis of advanced NSCLC patients is considered to be dependent on various prognostic factors. METHODS: We analyzed prognostic factors in patients with advanced NSCLC who had been enrolled in clinical trials conducted by the Okayama Lung Cancer Study Group between 1978 and 1992 using two kinds of multivariate analysis, Cox's multivariate analysis and recursive partitioning and amalgamation (RPA) analysis. RESULTS: The first analysis was performed on 261 patients using 28 variables. Performance status (PS), clinical stage, liver metastasis or serum albumin level was an independent prognostic factor by Cox's analysis. In the second analysis performed on 128 patients having data on neuron specific enolase (NSE), NSE was the most important prognostic factor. Using the RPA method, three subgroups with significantly different survival potentials were defined. Among them, patients with normal serum NSE levels and good PS were found to obtain a markedly favorable prognosis [median survival time (MST) 22.1 months, 3-year survival rate 42.9%], whereas the survival of patients with elevated serum NSE levels and bone metastasis was extremely short (MST 4.7 months, 3-year survival rate 0%). CONCLUSIONS: These results indicate that analysis of prognostic factors including serum levels of NSE is useful for predicting the survival of patients with advanced NSCLC. PMID- 11210163 TI - A phase II study of VP-16-fosfamide-cisplatin combination chemotherapy plus early concurrent thoracic irradiation for previously untreated limited small cell lung cancer. AB - BACKGROUND: At present the addition of thoracic irradiation to combination chemotherapy is a standard treatment for limited staged small cell lung cancer. However, there is still controversy about the optimum timing of chest irradiation. We conducted a phase II study of etoposide (VP-16)-ifosfamide cisplatin (VIP) combination chemotherapy plus early concurrent thoracic irradiation for the patients with previously untreated limited small cell lung cancer in order to assess if the treatment modality could improve the response rate and the toxicity. METHODS: Forty-four patients with limited small cell lung cancer were treated with etoposide-ifosfamide-cisplatin and concurrent thoracic irradiation. Combination chemotherapy consisted of etoposide 100 mg/m2 (on days 1 3), ifosfamide 1000 mg/m2 (on days 1 and 2) and cisplatin 100 mg/m2 (on day 1). Concurrent thoracic irradiation consisted of a total of 4000 cGy over 4 weeks starting on the first day of the first chemotherapy. All patients who showed a complete response were given prophylactic cranial irradiation for 2.5 weeks. RESULTS: Forty-four of the 49 patients who entered the study from May 1994 to August 1998 were evaluable. The median age was 59 years and 40 patients had a performance status of 0 or 1. The median survival time was 22.5 months. Twenty eight patients (62%) showed a complete response and 16 (38%) a partial response. Twenty-four patients (54%) developed grade 3 or 4 neutropenia; there was a 9% RTOG score 3 or 4 esophagitis. CONCLUSION: VIP combination chemotherapy and early concurrent thoracic irradiation for patients with limited stage small cell lung cancer revealed excellent antitumor response with tolerable toxicity. PMID- 11210164 TI - Single agent paclitaxel as a first-line therapy in advanced urothelial carcinoma: its efficacy and safety in patients even with pretreatment renal insufficiency. AB - BACKGROUND: Cisplatin-based chemotherapy is the mainstay of the treatment for advanced urothelial cancer, but patients with renal insufficiency before therapy are usually contraindicated to receiving platinum-based chemotherapy. Paclitaxel is one of the most promising agents against advanced urothelial carcinoma in recent trials and it can be easily tolerated even in patients with compromised renal function. We conducted a study in order to evaluate the efficacy and safety of paclitaxel as a first-line therapy in advanced urothelial carcinoma patients. METHODS: Thirteen advanced chemo-naive urothelial carcinoma patients with a median age of 71 years were studied, seven of them demonstrating renal insufficiency (pretreatment serum creatinine > or = 1.5 mg/dl). All 13 patients received a minimum of two cycles of paclitaxel 175 mg/m2, delivered by intravenous infusion for 3 h every 3 weeks. RESULTS: Four of the 13 patients responded to treatment, a response rate of 30.8%, with two of these achieving complete remission and two showing partial responses. The median overall survival period of all 13 patients was nine months (95% Cl: 6.51-11.49) and our study revealed a statistical tendency in the difference of median overall survival time between responders and non-responders (13 months versus 7.5 months, log-rank p = 0.038), although the number of cases was limited. The differences in response rate and median overall survival time, comparing patients with renal insufficiency and those with normal renal function, were not significant. Treatment-related toxicity was mild, with only two (15.4%) patients suffering from grade 3-4 leukopenia. No treatment-related mortality was noted. CONCLUSIONS: Single-agent paclitaxel can be used as a first-line therapy in advanced urothelial carcinoma patients, and is especially suitable for those with pretreatment renal insufficiency, since the antitumor activity is significant while toxicity is well tolerated. PMID- 11210165 TI - Preoperative concurrent chemoradiotherapy against muscle-invasive bladder cancer: results of partial cystectomy in elderly or high-risk patients. AB - BACKGROUND: Good local control has been reported in cases of muscle-invasive bladder cancer treated by chemoradiotherapy and transurethral resection (TUR). However, definitive irradiation or extensive chemotherapy is often intolerable for elderly or poor-risk patients. We report here benefits of partial cystectomy after concurrent low-dose chemoradiotherapy for high-risk patients. METHODS: Thirty-seven patients with localized muscle-invasive bladder cancer (T2-T4) were treated with concurrent cisplatin (50-100 mg/body x 2 courses) and pelvic irradiation (40 Gy) preoperatively. Among 17 patients (46%) who achieved complete response (CR), 10 were not suitable for radical cystectomy and underwent partial cystectomy. Radical cystectomy was performed in 24 cases [CR = 6, partial response (PR) = 18]. Two patients (one CR and one PR) rejected open surgery and were treated by TUR of the primary site. One no change (NC) patient received no further treatment because of mental disorder. RESULTS: Median follow-up was 12 months (range 2-37 months). Fifteen of 36 evaluable cases (42%) achieved a pathological T0 response (no residual tumor). Estimated 3-year disease-free survival was 56% for all patients and 100% for T0 responders. Seven of 21 patients with pathological persistent tumor developed local recurrence (three patients) or distant metastasis (four patients). All of the 10 patients (eight with T0 response and two with a small residual tumor nest) who underwent partial cystectomy were recurrence-free for an observation period of up to 3 years. CONCLUSIONS: Bladder preservation by partial cystectomy may be a choice for patients who show a good response to preoperative chemoradiotherapy and are not suitable for radical cystectomy. PMID- 11210166 TI - Statistical analysis of geographical features of lung cancer mortality in Japan. AB - BACKGROUND: There is concern about the increase in death rates from lung cancer and that it may become the leading cause of death in the near future. Considerable geographical variations exist in lung cancer mortality in Japan. It seems that the difference cannot be explained by smoking rates, although no data are available to prove this. The evidence implies some unknown risk factors in the development of lung cancer. As an alternative approach, we used geographical or demographic information according to municipality. To explore other factors in lung cancer development, the geographical features of trends in lung cancer mortality in Japan were examined using long-term data. METHODS: We summarized the 20-year municipality-specific standardized mortality ratios (SMRs) by fitting a straight line to the scatter plot of the SMR versus calendar year for each municipality, resulting in an average and a rate of change of SMR. Using the average or rate of change in the SMR as the response variable, we carried out a multiple linear regression analysis for all of Japan and a non-parametric regression analysis for the distance from the municipal office to the nearest coastline, using the ACE algorithm. RESULTS: The average SMR decreased with distance from the coastline and increased with increasing population size of the municipality. The average SMR was high at or near the coastline irrespective of the direction of the nearest coastline. CONCLUSIONS: It was considered that something related to coastline other than population size may be associated with the development of lung cancer. PMID- 11210167 TI - Comparison of in vitro growth-inhibitory activity of carboplatin and cisplatin on leukemic cells and hematopoietic progenitors: the myelosuppressive activity of carboplatin may be greater than its antileukemic effect. AB - BACKGROUND: Carboplatin [cis-diammine(cyclobutane-1, 1 dicarboxylato)platinum(II)] has been shown to be an active agent for acute myeloid leukemia. This second-generation platinum drug has less nephrotoxicity and ototoxicity but more myelotoxicity than does the first-generation platinum drug cisplatin. The study was designed to elucidate whether their myelosuppressive activities equal their antileukemic effects. METHODS: Cisplatin and carboplatin were used to treat four leukemic cell lines (CEM, HL60, K562 and U937), blast cells from 10 leukemic patients and hematopoietic progenitors from five umbilical cord blood samples. RESULTS: The mean IC50 of leukemic cell lines was 0.4 and 6.2 microg/ml, the mean IC50 of patients' leukemic blasts was 2.0 and 22.4 microg/ml and the mean IC50 of hematopoietic progenitors (BFU-E, CFU-E and CFU-GM) was 1.8 and 1.7 microg/ml for cisplatin and carboplatin, respectively. CONCLUSIONS: Carboplatin required a 10 times higher drug concentration than cisplatin to induce a similar degree of growth inhibition on leukemic cells. However, the hematopoietic progenitors responded equally to cisplatin and carboplatin at the same drug concentration. The results suggest that the myelosuppressive activity of carboplatin is greater than its antileukemic effect. PMID- 11210168 TI - Does alcohol drinking have an influence on suicides in cancer sufferers? A population-based study of 1515 suicide victims. AB - BACKGROUND: [corrected] We investigated whether alcohol drinking contributes to suicides in cancer sufferers when compared with non-cancer suicides. We also explored the suicide method used in cancer suicides. METHODS: The population based, prospectively collected data sample consisted of 1515 completed suicides committed in the province of Oulu, Finland, during the period 1988-99. Victims who suffered from cancer were compared with other suicides. RESULTS: Cancer patients who committed suicide were significantly less commonly under the influence of alcohol than non-cancer suicide victims (84.8% vs 54.7%). Mental disorders were less prevalent among cancer patients than non-cancer patients. The cancer patients were significantly older and more often retired and a trend that a greater proportion of cancer suicide victims were male was noted. Shooting and poisoning were the most common suicide methods among cancer patients. CONCLUSION: An early recognition and evaluation of the extent of the suicidal tendencies among cancer patients is of great importance in clinical oncology, since preventive interventions would be effective especially for those without comorbid alcoholism at the time of the suicide. PMID- 11210169 TI - Two cases of non-Hodgkin's lymphoma in first degree relatives. AB - Two cases of non-Hodgkin's lymphoma (NHL) generated within 6 months in first degree relatives, a father and a son, are presented. The NHL was a diffuse large B-cell type in the father and a small cleaved follicular type in the son. Cytogenetic and molecular studies of the lymphoma cells revealed the rearrangement of the immunoglobulin heavy chain (JH) gene in both patients, the mutation of p53 gene in the father and t(14; 18) (q32; q21) in the son. Both patients had low serum immunoglobulin levels. It is not known whether the occurrence of NHL in this family was incidental or pathogenetically related, since there was no clear common molecular abnormality between the father and the son. The pathogenetic mechanism of this familial occurrence of NHL is discussed. PMID- 11210170 TI - Biliary tract cancer mortality rates by prefectures in Japan. PMID- 11210171 TI - Aberrant methylation of genes in low-grade astrocytomas. AB - The underlying basis of the malignant progression of astrocytomas is a specific and cumulative series of genetic alterations, most of which are confined to high grade tumors. In contrast, a proportion of low-grade astrocytomas have a relatively normal-appearing genome when examined with standard genetic screening methods. These methods do not detect epigenetic events such as aberrant methylation of CpG island, which result in transcriptional silencing of important cancer genes. To determine if aberrant methylation is involved in the early stages of astrocytoma development, we assessed the methylation status of 1,184 genes in each of 14 low-grade astrocytomas using restriction landmark genome scanning (RLGS). The results showed nonrandom and astrocytoma-specific patterns of aberrantly methylated genes. We estimate that an average of 1,544 CpG island associated genes (range, 38 to 3,731) of the approximately 45,000 in the genome are aberrantly methylated in each tumor. Expression of a significant proportion of the genes could be reactivated by 5-aza-2-deoxycytidine-induced demethylation in cultured glioma cell lines. The data suggest that aberrant methylation of genes is more prevalent than genetic alterations and may have consequences for the development of low-grade astrocytomas. PMID- 11210172 TI - Presurgical mapping with magnetic source imaging: comparisons with intraoperative findings. AB - We compare noninvasive preoperative mapping with magnetic source imaging to intraoperative cortical stimulation mapping. These techniques were directly compared in 17 patients who underwent preoperative and postoperative somatosensory mapping of a total of 22 comparable anatomic sites (digits, face). Our findings are presented in the context of previous studies that used magnetic source imaging and functional magnetic resonance imaging as noninvasive surrogates of intraoperative mapping for the identification of sensorimotor and language-specific brain functional centers in patients with brain tumors. We found that magnetic source imaging results were reasonably concordant with intraoperative mapping findings in over 90% of cases, and that concordance could be defined as "good" in 77% of cases. Magnetic source imaging therefore provides a viable, if coarse, identification of somatosensory areas and, consequently, can guide and reduce the time taken for intraoperative mapping procedures. PMID- 11210173 TI - Alterations of the p53 and pRB pathways in human astrocytoma. AB - Human astrocytomas are characterized by a number of molecular changes affecting two critical tumor suppressor pathways: the pRB and the p53 pathways. Genetic alterations functionally eliminate pRB and p53 themselves or upstream and/or downstream molecules such as products of the Ink4a/ARF locus, p16Ink4a and p14ARF. As a result, malignant cells are defective in critical cell cycle and apoptosis regulatory elements contributing to unrelenting tumour growth and invasion. Current research aims to discover effective means of reconstituting p53 and pRB pathway components in an effort to attenuate the aggressive phenotype of astrocytoma. PMID- 11210174 TI - EGFRvIII as a promising target for antibody-based brain tumor therapy. AB - Cell surface receptors are attractive candidates for targeted therapy of cancer. Growth factors and their receptors play important roles in the regulation of cell division, development, and differentiation. Among those, the epidermal growth factor receptor (EGFR) was the first identified to be amplified and/or rearranged in malignant gliomas. The most common rearranged form, EGFR type III variant (EGFRvIII), has a deletion in its extracellular domain that results in the formation of a new, tumor-specific target found in glioblastoma multiforme, as well as in breast, ovarian, prostate, and lung carcinomas. Monoclonal antibodies have been developed with specific activity against this mutant receptor. These antibodies are internalized into the cell after receptor binding. Specific antibodies, either unarmed or armed with cytotoxic agents, including radioisotopes and toxins, have shown a promising role for EGFRvIII as a target for brain tumor therapy. PMID- 11210175 TI - Analysis of neuropathological images. PMID- 11210176 TI - A neurosurgeon's perspective on the neuropathology of low-grade gliomas. PMID- 11210177 TI - Brain tumor radiosurgery: current status and strategies to enhance the effect of radiosurgery. PMID- 11210178 TI - Length of uninterrupted repeats determines instability at the unstable mouse expanded simple tandem repeat family MMS10 derived from independent SINE B1 elements. AB - Mouse expanded simple tandem repeats (ESTRs) provide highly informative loci for analyzing spontaneous and induced germline mutation. We have conducted an extensive sequence database search and identified 17 new members of the highly unstable rodent-specific ESTR family called MMS10. This family has arisen by independent expansions of a common GGCAGA repeat unit from within a subset of both ancestral and modern SINE B1 elements during the course of mouse evolution. Analysis of the interspersion patterns of variant repeats along alleles of 20 of these MMS10 loci revealed two distinct classes of tandem arrays: one composed of uninterrupted GGCAGA repeats and the second with generally larger arrays interrupted by variant units. Surveys of allelic diversity at 11 representative members of these two classes of loci in various laboratory strains and BXD recombinant inbred lines revealed that the level of repeat instability was positively correlated with the length of uninterrupted repeats. Turnover processes at MMS10 loci, therefore, appear similar to the type of mechanism observed at human microsatellites. The MMS10 family thus provides a potentially useful murine model for studying dynamic mutation at simple tandem repeats. PMID- 11210179 TI - Smcy transgene does not rescue spermatogenesis in sex-reversed mice. AB - In mouse, the Sxr(b) deletion interval (delta Sxr(b)) maps to the small short arm of the Y chromosome and is known to contain gene(s) required for normal spermatogenesis; in particular, Spy, which is essential for the postnatal mitotic proliferation of spermatogonia. This deletion interval is approximately 1-2 Mb and contains eight known genes. In this paper we report the construction of YAC transgenic mice containing different regions of the delta Sxr(b) interval including Zfy1, Ube1y, Smcy, and Eif2s3. Two male and one female founder mice, transgenic for all four genes, were sterile. However, a fertile transgenic, carrying a full-length copy of the Smcy gene integrated into central Chr 12, was identified. Smcy is a highly conserved Y chromosome-located gene, encoding peptides corresponding to epitopes of the male-specific antigen, H-Y. The Smcy transgene was ubiquitously expressed in all organs and tissues tested in male and female carriers. Introduction of the transgene into an X Sxr(b)/O genetic background did not rescue the early arrest of spermatogenesis characteristic of these males. These data indicate that the presence of Smcy is not sufficient to restore spermatogenesis, making it a highly unlikely candidate for Spy. PMID- 11210181 TI - Submucosal gland distribution in the mouse has a genetic determination localized on chromosome 9. AB - Submucosal glands (SMG) are important secretory glands that are present in the major airways and bronchioles of humans. In mice the structure, cellular composition, and density of SMG are similar to those seen in humans, but the glands are present only in the trachea. Characterization of SMG is important as they secrete bacteriocidal products such as lactoferrin, lysozyme, and defensins believed to be of importance in the innate defense system. Serous cells in SMG are the primary site of cystic fibrosis transmembrane conductance regulator (CFTR) gene expression and the initial site of histological abnormality in cystic fibrosis (CF) individuals. In this study, we examined four inbred strains of mice (A/J, C57BL/6N, FVB/N, and BALB/CAnN) and revealed that the extent to which glands descend in the mouse trachea varied between inbred strains. In particular, the A/J and C57BL/6N strains exhibited few SMG extending further than the first or second intercartilaginous space (mean depth of 0.4+/-0.11 and 1.5+/-0.32 tracheal rings respectively) in the trachea, whereas the FVB/N and BALB/CAnN strains had SMG extending beyond the fourth space (mean depths of 3.3+/-0.46 and 5.6+/-0.45 rings respectively). We have previously shown that in congenic C57Bl/ 6N Cftr mutant mice (CF mice), the SMG are distributed more distally than in wild type C57Bl/6N but are indistinguishable from BALB/CAnN wild-type or CF mice. The implication that SMG distribution is influenced by Cftr gene expression (or a gene closely linked to Cftr) led us to investigate the genetic difference between C57Bl6/N and BALB/CAnN mice. In recombinant inbred strain (RIS) analysis (with BALB/CJ and C57BL/6J progenitors), two loci were identified as being linked to the SMG phenotype (peak likelihood statistic levels of 8.8 and 9.9 on Chrs 9 and 10 respectively, indicating suggestive linkage). A subsequent segregation analysis of an F2 intercross between the C57BL/6N and BALB/CAnN mice indicated that there were at least two major genetic factors responsible for SMG distribution. The loci indicated in the RI analysis were included in a targeted genome scan involving 235 F2 intercross animals (C57BL/6N and BALB/CAnN strain intercross). The genome scan confirmed the locus on Chr 9 (between genetic markers D9Mit11 and D9Mit182), designated Smgdl, as significantly linked to the SMG distribution phenotype (peak LOD score 5.8) within a 95% confidence interval of 12 cM. PMID- 11210180 TI - Cloning, expression, genomic localization, and enzymatic activities of the mouse homolog of prostate-specific membrane antigen/NAALADase/folate hydrolase. AB - Human Prostate Specific Membrane Antigen (PSMA), also known as folate hydrolase I (FOLH1), is a 750-amino acid type II membrane glycoprotein, which is primarily expressed in normal human prostate epithelium and is upregulated in prostate cancer, including metastatic disease. We have cloned and sequenced the mouse homolog of PSMA, which we have termed Folh1, and have found that it is not expressed in the mouse prostate, but primarily in the brain and kidney. We have demonstrated that Folh1, like its human counterpart, is a glutamate-preferring carboxypeptidase, which has at least two enzymatic activities: (1) N-acetylated alpha-linked L-amino dipeptidase (NAALADase), an enzyme involved in regulation of excitatory signaling in the brain, and (2) a gamma-glutamyl carboxypeptidase (folate hydrolase). The 2,256-nt open reading frame of Folh1 encodes for a 752 amino acid protein, with 86% identity and 91% similarity to the human PSMA amino acid sequence. Cells transfected with Folh1 gained both NAALADase and folate hydrolase activities. Examination of tissues for NAALADase activity correlated with the mRNA expression pattern for Folh1. Fluorescent in situ hybridization (FISH) revealed Folh1 maps to only one locus in the mouse genome, Chromosome 7D1 2. PMID- 11210182 TI - Murine phosphatidylserine-specific phospholipase A1 (Ps-pla1) maps to chromosome 16 but is distinct from the lpd (lipid defect) locus. AB - We have previously generated a mouse transgenic line with an insertional mutation designated lpd that demonstrates a phenotype of hypertriglyceridemia and fatty liver. Since the recently identified phosphatidylserine-specific phospholipase A1 (PS-PLA1) demonstrates significant homology to triglyceride lipases, we reasoned that the mouse Ps-plaI gene may be the disrupted gene within the lpd locus. Using a rat PS-PLA1 cDNA sequence to search the EST database, we identified a mouse EST homolog AA839424. Sequencing analysis of AA839424 revealed a putative Ps-pla1 protein of 456 amino acids with extensive overall structural conservation with human and rat PS-PLA1 and with triglyceride lipases. Conserved sequences in Ps pla1 include a lipase consensus sequences GxSxG, a catalytic triad, and eight of the ten conserved cysteine residues that are required for tertiary structure. Mouse Ps-plal carries a phosphatidylserine-binding motif that is absent in all triglyceride lipases. Using a mouse whole-genome radiation hybrid (WG-RH) mapping panel (T31), we mapped mouse Ps-pla1 to Chromosome (Chr) 16 between genetic markers D16Mit194 and D16Mit38, which is 17.1 cM centromeric to the lpd locus. On the basis of chromosome location, we conclude that Ps-pla1 and lpd are distinct genes in lipid metabolism. PMID- 11210183 TI - The murine chaperonin 10 gene family contains an intronless, putative gene for early pregnancy factor, Cpn10-rs1. AB - Early pregnancy factor (EPF) is a secreted protein with growth regulatory and immunomodulatory properties. Human platelet-derived EPF shares amino acid sequence identity with chaperonin 10 (Cpn10), a mitochondrial matrix protein which functions as a molecular chaperone. The striking differences in cellular localization and function of the two proteins suggest differential regulation of production reflecting either alternative transcription of the same gene or transcription from different genes. In mammals and more distantly related genera, there is a large gene family with homology to CPN10 cDNA, which includes intronless copies of the coding sequence. To determine whether this could represent the gene for EPF, we have screened a mouse genomic library and sequenced representative Cpn10 family members, looking for a functional gene distinct from that of Cpn10, which could encode EPF. Eight distinct genes were identified. Cpn10 contains introns, while other members are intronless. Six of these appear to be pseudogenes, and the remaining member, Cpn10-rs1, would encode a full-length protein. The 309-bp open reading frame (ORF) is identical to that of mouse Cpn10 cDNA with the exception of three single-base changes, two resulting in amino acid changes. Only one further single nucleotide difference between the Cpn10-rs1 and Cpn10 cDNAs is observed, located in the 3' UTR. Single nucleotide primer extension was applied to discriminate between Cpn10-rs1 and Cpn10 expression. Cpn10, which is ubiquitous, was detected in all tissue samples tested, whereas Cpn10-rs1 was expressed selectively. The pattern was completely coincident with known patterns of EPF activity, strongly suggesting that Cpn10 rs1 does encode EPF. The complete ORF of Cpn10-rs1 was expressed in E. coli. The purified recombinant protein was found to be equipotent with native human platelet-derived EPF in the bioassay for EPF, the rosette inhibition test. PMID- 11210184 TI - Fine-mapping and construction of a bovine contig spanning the ovine callipyge locus. AB - The callipyge (CLPG) gene was fine-mapped by linkage analysis to a 4.6-cM chromosome interval on distal ovine OAR18q, flanked by microsatellite markers IDVGA30 and OY3. The OAR18q linkage map and human HSA14q transcript map were aligned by genotyping two bovine-hamster whole-genome radiation hybrid panels with the microsatellite markers, as well as with sequences corresponding to HSA 14q genes. Using Type I loci mapping to the IDVGA30-OY3 interval as anchor points, we have constructed a 1.4-Mb bovine BAC contig containing the IDVGA30-OY3 interval. We demonstrate that the IDVGA30-OY3 interval spans approximately 770 kb and contains at least four genes: YY1, WARS, DLK1, and GTL2. PMID- 11210185 TI - Isolation and molecular characterization of rasfadin, a novel gene in the vicinity of the bovine prion gene. AB - A novel gene, rasfadin (RASSF2) was identified close to the bovine prion gene, and its genomic structure was derived with a combination of exon trapping and RACE. The gene covers at least 28 kb and maps to the same chromosomal region as the prion gene in cattle, sheep, and human. The RASSF2 ORF is composed of 987 base pairs divided into nine exons and shows a high nucleotide (88%) and amino acid similarity (95%) with a previously described human cDNA, KIAA0168. The bovine 3'UTR region is significantly shorter than the human counterpart, but shares with it two highly conserved nucleotide blocks. The expression of the gene was investigated in brain, liver, and spleen. Alternative splicing yields a shorter product in the liver composed of only four exons. Computer analysis showed a highly significant similarity of the rasfadin protein with the Ras association (Ral-GDS/AF-6) domain family 2 and with the afadin family, respectively, for the longer brain/spleen and the shorter liver variants. PMID- 11210186 TI - Cloning, expression and chromosomal location of NKX6B TO 10Q26, a region frequently deleted in brain tumors. AB - Nkx6-2 (former Gtx) is a murine-homeobox-containing gene localized distally on Chromosome (Chr) 7. Analysis of the expression pattern, together with DNA binding assays, suggests that this gene product might be important for differentiated oligodendrocyte function and in the regulation of myelin gene expression. We now report on the cloning and characterization of the human homolog (NKX6B). DNA sequence analysis of an 11-kb genomic fragment revealed that the complete human gene spans 1.2 kb and is composed of three exons. NKX6B is predicted to encode a polypeptide of 277 amino acids with 97% identity to mouse Nkx6-2. Northern blot experiments showed that NKX6B expression is tightly controlled in a tissue specific fashion with the highest site of expression being the brain. Finally, using STS content mapping and RH analyis, we demonstrated that NKX6B maps to the 10q26, a region where frequent loss of heterozygosity has been observed in various malignant brain tumors. These results may implicate NKX6B as a candidate tumor suppressor gene for brain tumors, particularly for oligodendrogliomas. PMID- 11210187 TI - Gene structure alternative splicing, and chromosomal localization of pro apoptotic Bcl-2 relative Bim. AB - Bim is a proapoptotic protein of the Bcl-2 family that shares only the short BH3 domain with other members. It has three isoforms, apparently produced by alternative splicing. The demonstration that Bim is essential for certain apoptotic responses and to prevent overproduction of hematopoietic cells suggests that it may be a tumor suppressor. We have, therefore, investigated the organization of the mouse Bim gene, delineating its promoter and splicing, and positioned the gene on both mouse and human chromosomes. Bim has six exons, but the third is a facultative intron that is spliced out in the mRNAs for the smaller isoforms (BimL and BimS), but not that encoding the largest isoform (BimEL). The 0.8-kb region 5' to exon 1, which contains a TATA-less promoter and binding sites for several transcription factors, can drive expression of a reporter gene. Mouse Bim localizes to the distal third of Chromosome (Chr) 2, near the F-G boundary, and its human counterpart to Chr 2q12 or q13. Deletions of these bands have been reported in ten tumors (eight hematopoietic), reinforcing the possibility that Bim is a tumor suppressor. These findings should help to clarify the regulation of Bim expression and to assess whether mutations involving Bim contribute to neoplastic and other diseases. PMID- 11210188 TI - Transgenic mice for the preparation of puromycin-resistant primary embryonic fibroblast feeder layers for embryonic stem cell selection. PMID- 11210189 TI - Identification of a novel, alternatively spliced isoform and single nucleotide polymorphisms in the murine Pea-15 gene. PMID- 11210190 TI - The murine type 1 diabetes loci, Idd1, Idd3, Idd5, Idd9, and Idd17/10/18, do not control thymic CD4-CD8-/TCRalphabeta+ deficiency in the nonobese diabetic mouse. PMID- 11210191 TI - Identification, expression analysis, and mapping of B3galt6, a putative galactosyl transferase gene with similarity to Drosophila brainiac. PMID- 11210192 TI - Genetic mapping of spinal dysmyelination in cross-bred American Brown Swiss cattle to bovine Chromosome 11. PMID- 11210193 TI - Breakpoint mapping positions the callipyge gene within a 450-kilobase chromosome segment containing the DLK1 and GTL2 genes. PMID- 11210194 TI - 129/Sv mice--a model system for studying germ cell biology and testicular cancer. AB - Some forms of testicular germ cell tumors (TGCTs) arise from primordial germ cells (PGCs) during fetal development. In both humans and mice, genetic control of susceptibility is complex, involving both Mendelian and polygenic factors. Identification and characterization of TGCT genes will provide insight not only into the basis for inherited susceptibility, but also into the genetic control of the development of the PGC lineage. Recent work has revealed the identity of several susceptibility genes that are inherited as Mendelian traits, the chromosomal location of yet-to-be identified TGCT susceptibility genes, as well as clues to the nature of developmental pathways involved in tumorigenesis. In this review we summarize current understanding of the biology and genetics of TGCTs in mice and discuss the relevance of this work to testicular cancer in humans. PMID- 11210195 TI - Multiple obesity QTLs identified in an intercross between the NZO (New Zealand obese) and the SM (small) mouse strains. AB - The inheritance of adiposity levels has been investigated in an intercross of the obese, diabetes-prone NZO and the small, lean SM mouse strains. Adiposity index (AI) was defined as the sum of four fat pad weights divided by body weight. DNA pools from fat and lean mice were analyzed with microsatellite variants to screen the genome for quantitative trait loci (QTLs) affecting AI. Ten significant QTLs affecting AI were identified on Chromosome (Chr) 1 (three loci), Chr 2, Chr 5 (two loci), Chr 6 (two loci), Chr 7, and Chr 17. Most of the QTLs appear to be novel. Several QTLs differentially affect specific fat depots. Thus, Chr 2 and Chr 7 QTLs affect gonadal more than inguinal fat, while the converse is true for the Chr 17 QTL. Gender influences the expression of several of the QTLs. For example, effects of the proximal Chr 1 QTL (Obq7) on AI appears to be primarily in males. The proximal AI QTL on Chr 6 (Obq13) maps near the neuropeptide Y (Npy) locus. Sequence analysis of the Npy gene revealed a 1-nucleotide deletion within a highly conserved portion of the 3' untranslated region in strain NZO. However, the deletion is polymorphic among mouse strains. Furthermore, lack of association between this same variant and AI in previously analyzed crosses raises doubt that it is the basis of Obq13. The present cross is the fourth in a series of intercrosses among 10 inbred strains arranged such that each strain is crossed with each adjacent strain within a circle. This design affords multiple opportunities to analyze each segregating QTL. PMID- 11210196 TI - CCCSAPR: a new approach to drug policy research in the twenty-first century. California Collaborative Center for Substance Abuse Policy Research. AB - The California Collaborative Center for Substance Abuse Policy Research (CCCSAPR) was established in 1997 to provide a nucleus for policy research in addiction and allied fields throughout the nine University of California campuses and allied research endeavors. The primary goal of CCCSAPR is that of providing data on statewide and national substance abuse issues toward the development and maintaining of a coherent substance abuse policy in the state of California. The authors present the history and scope of the Center as a new approach to drug policy research for a new century. PMID- 11210197 TI - Drug abuse treatment on demand in San Francisco: preliminary findings. AB - This article reports on a process and capacity evaluation of San Francisco's Treatment on Demand Initiative, which was launched in 1997 to increase availability of publicly-funded substance abuse treatment. For the process evaluation, data from public documents, interviews with community key informants, and newspaper articles were analyzed. For the capacity evaluation, budget documents and admissions data for publicly-funded substance abuse treatment in San Francisco for fiscal years 1995-1998 were analyzed. Results from the process evaluation document the development of the community-oriented Treatment on Demand Planning Council, and its efforts to not only expand treatment, but to create a continuum of services to address the needs of San Francisco's richly diverse communities, to provide service enhancements, and to prioritize service needs. Process evaluation results also highlight the complexities of implementing treatment on demand, including the difficulty of opening new programs. Results from the capacity evaluation indicate that the San Francisco budget supporting publicly-funded treatment increased from $32 million to $45.2 million over four years. During the same period, the number of persons entering the system in a single year increased by 18%, and the number of admissions in a single year increased by 15%. Implications of these findings are discussed. PMID- 11210198 TI - Addiction pharmacotherapy 2000: new options, new challenges. AB - There are many indicators that substance abuse research and treatment are going to become better integrated. Hopefully, this development will produce new treatment options and will improve access and effectiveness of care. Among the most significant factors in this period of change are the advances in addiction pharmacotherapy. For the treatment of alcoholism, disulfiram has been joined by naltrexone, and soon acamprosate will be added to the list of available pharmacotherapies. Individuals with opiate dependence who, for 25 years, were limited to a single medication (methadone) now have LAAM as an available treatment. Furthermore, there is eager anticipation that buprenorphine/naloxone will bring many more opiate users into treatment since it appears that this medication will be available to doctors outside the traditional narcotics treatment program settings. Other opiate addiction treatment options, including sustained-release naltrexone and lofexidine, are in active development. The greatest area of challenge for pharmacotherapy research is the search for stimulant addiction medications. NIDA has extensive efforts underway to discover/develop medicines that can help in the treatment of cocaine and methamphetamine users. During the next decade, those who embrace these new treatments and integrate them into standard care will offer their patients the best chance for recovery. PMID- 11210199 TI - Bridging the gap between research and drug abuse treatment. AB - There is a gulf between researchers and practitioners, due in part to conditions that existed before they began training, and partially due to their continued separation during training and practice. This article reviews some of the differences and offers suggestions for institutional and personal changes to bring researchers and practitioners more into accord. PMID- 11210200 TI - Severely and persistently mentally ill substance abusers: clinical and policy issues. AB - Communities that are struggling to provide effective treatment for the challenging population of severely mentally ill clients who use alcohol and drugs have a growing research base on which to make policy decisions. Integrating outpatient treatment for mental health and addictive disorders appears to be more effective than treatment in two separate systems. Integrated treatment at a single site allows for individualizing treatment priorities without fragmenting care. Harm reduction approaches provide a low threshold entry, which can be followed by interventions to enhance motivation. Managing patient benefits to discourage drug use reduces the likelihood of their becoming homeless, hospitalized or incarcerated. Inadequate treatment capacity plays a large role in the growing number of disturbed clients who end up in the criminal justice system. Effective community treatment requires vigorous collaboration between care providers. Ultimately, professional training programs need to produce clinicians who are competent and comfortable addressing alcohol and other drug use to implement effective treatment systems. PMID- 11210202 TI - Concepts of dependence among Brazilian alcohol- and drug-dependent patients. AB - Studies suggest that the concepts that drug dependent persons have about their problems could influence adherence to treatment and outcome. The objective of this study was to compare these concepts in different groups of patients. Three groups of drug-dependent patients (diagnosed according to DSM-III-R criteria) were compared: 64 dependent on alcohol only, 56 dependent only on other drugs and 39 dependent on both alcohol and drugs. They were asked: "What do you think about your problem?" and the responses were qualitatively analyzed and classified into themes. For the whole sample, the main themes mentioned were: the function of alcohol and drugs in their lives (50%), the etiology of dependence (32%) and reasons for initial use (21%). Patients dependent on alcohol associated their use with coping, while patients dependent on other drugs reported pleasure seeking. In regard to etiology, most patients classified their dependence as a habit. Patients dependent on alcohol tended to attribute an organic etiology to their problem, while those dependent on other drugs most frequently considered moral aspects as important. This study suggests that there are differences between these three groups in the appraisal of their problem. Professionals interested in treatment matching need to take these findings into account, as they may influence compliance and treatment outcome. PMID- 11210201 TI - The relationship between crime and drugs: what we have learned in recent decades. AB - The focus of this article is criminal drug users and their changing behavior. Two important considerations are addressed within this topic. First, an overview of drug use is given, including a brief historical perspective on its treatment as well as its implications on crime. The article also discusses why substance abuse treatment in the criminal population is necessary and on what scale. Specifically, the etiology of the relationship between crime, violence and substance abuse is explored. It then delves into what has worked and what hasn't. Finally, recommendations are made regarding where the research indicates we should go from here. PMID- 11210203 TI - Retrospective study of similarities and relations between American drug-free and European therapeutic communities for children and adults. AB - This article focuses on the similarities and relations between the European therapeutic community for children and adults on the one hand and the American drug-free "concept" therapeutic community on the other. Both approaches are reviewed in a historical and comparative perspective with special attention to several critical issues: democracy versus hierarchy, self-help versus professionalism, psychoanalysis versus behaviorism and concept versus social learning. These two different TC-approaches can be considered as subdivisions of one modality, namely an environment for social learning in which living together in a group can be regarded as the primary agent of growth and human development. In recent years there has been a tendency towards further integration of these two approaches. PMID- 11210204 TI - A review of the nonmedical use of ketamine: use, users and consequences. AB - Ketamine is a dissociative anesthetic with an accepted place in human medicine. Ketamine also has psychedelic properties, and there has been a recent increase in nonmedical use linked with the growth of the "dance culture." This has attracted little comment in the formal literature but has been the subject of many reports in the media. Myths and misunderstandings are common. The psychedelic properties of ketamine have also led to its use as an adjunct to psychotherapy. This review is intended as a resource for the wide range of persons now requesting accurate information about the nonmedical use of ketamine. It accepts the current necessity of sometimes referring to anecdotal reports while seeking to encourage an increase in formal research. The review includes the history of ketamine, its growing role as a "dance drug," the sought-after effects (including the near death experience) for which it is taken in a nonmedical context, how these are produced, common mental and physical adverse effects, and the ketamine model of schizophrenia. PMID- 11210205 TI - Who is using cannabis as a medicine and why: an exploratory study. AB - This article reports on an exploratory study of medical cannabis users. Interviews were completed with 50 self-identified medical cannabis users recruited through notices in newspapers and on bulletin boards. They reported using cannabis for a variety of conditions including HIV-AIDS-related problems, chronic pain, depression, anxiety, menstrual cramps, migraine, narcotic addiction as well as everyday aches, pains, stresses and sleeping difficulties. A majority also used cannabis for recreational purposes, and many were longer-term cannabis users. However, there were some notable exceptions. Almost all smoked cannabis and many did so two to three times a day. Few admitted negative experiences with cannabis, although some problems evident to the researchers were not clearly admitted. Those who told their doctors about their medical cannabis use found doctors noncommittal or supportive. The results raise questions about the definition of medical cannabis use and about policies that might be developed to accommodate such use. Limitations of the study are noted and further research suggested. Research priorities include population surveys, studies involving larger, more representative samples of medical cannabis users and studies of medical cannabis use among people with HIV-AIDS. PMID- 11210206 TI - Social relationships of crime-involved women cocaine users. AB - Social relationships play a significant role in drug use and recovery, perhaps especially for women. Research on social relationships among crime-involved women drug users is reviewed, including both well established findings and more recent topics of inquiry. Several open questions about social relationships of women drug users are then examined in data from a study conducted in the Miami (Florida) metropolitan area in 1994-1996. For a study of barriers to drug treatment for crime-involved women cocaine users, over 400 women were interviewed in treatment programs and an equal number were recruited on the street. Respondents were asked about their social relationships during the last 30 days on the street in regard to both legal and illegal activities. This included crime partnerships, help obtaining cocaine, living arrangements, help with living expenses, children and help with child care, help with several ordinary problems, and pressures to enter treatment. The analysis looks at how much social support crime-involved women cocaine users have in their ordinary daily activities, who provides this support, and findings from this data set relative to open questions in the literature. PMID- 11210208 TI - Knowledge always on call: for docs, practicing medicine will mean providing information more than providing care. PMID- 11210207 TI - Corona mortis: an anatomic study in seven cadavers and an endoscopic study in 28 patients. AB - BACKGROUND: The corona mortis is defined as the vascular connections between the obturator and external iliac systems. While detailed information on the arterial anastomoses in corona mortis is available, a complete description of the venous system is lacking. Although the tiny anastomoses behind the pubic symphysis between the obturator and external iliac arteries have been described in classical anatomy textbooks, these texts neglect to mention that these anastomoses can be life threatening. Attention needs to be paid to these anastomoses between the arterial and the venous system located over the superior pubic ramus during laparoscopic procedures. METHODS: Fifty retroinguinal regions were dissected in seven cadavers and 28 patients. RESULTS: During the dissections, a venous anastomosis on the superior pubic ramus was a consistent finding in 96% of cases. This vein coursed vertically to the inferior border of the superior pubic ramus and connected to the obturator vein. Accessory branches of the obturator artery were observed in only 8% of the dissections. The tiny connections between the obturator and external iliac arteries are less important, since their diameter is <1 mm. CONCLUSIONS: We have termed the venous connection between the external iliac and obturator veins over the superior pubic ramus "the communicating vein". This structure forms the corona mortis. Surgeons dealing with direct, indirect, femoral, or obturator hernias need to be aware of these anastomoses and their close proximity to the femoral ring. In classical anatomy textbooks, a description of the veins that form corona mortis is found less often than descriptions of the arteries. Since a venous connection is more probable than an arterial one, its importance must be appreciated by surgeons in order to avoid venous bleeding. PMID- 11210209 TI - How to successfully influence laboratory test utilization. AB - In 1994, we discovered that our hospital was higher than the 75th percentile in the average number of laboratory tests performed per inpatient discharge compared with other teaching hospitals with a case mix index of greater than 1.35. Because of the diversity and volume of tests offered, no single project would have significantly affected the number of tests ordered per patient. Pathologists together with the administrative director and section managers identified areas of potential improvement, noting tests that were high volume, expensive, difficult to perform, or of questionable medical benefit. We relied on a combination of administrative changes and physician education initiatives to influence physician test-ordering behavior. The impact of these initiatives was measured by reviewing monthly revenue and usage reports before and after changes were implemented. Each of these initiatives helped to gradually decrease the average number of inpatient tests per discharge from 44 in the first quarter of 1994 to 29 in the third quarter of 1999. Compared with our peer group, our hospital's rank has steadily improved from the 75th to the 15th percentile. PMID- 11210210 TI - Direct access testing in the clinical laboratory: should laboratories offer testing services directly to the consumer? AB - This article outlines the author's views on the many issues to consider if a laboratory plans to initiate a program to offer clinical laboratory testing directly to the public. Direct access testing and why is it important are discussed in detail. The regulatory issues are outlined with some alternatives for laboratories in states with restrictive regulations. To illustrate many of the operational issues to consider, the author describes the Personal Diagnostic Center (PDC) in Kansas City. Finally, some of the key business issues are mentioned, including several approaches to promote this type of testing program. PMID- 11210212 TI - Integrated reporting and interpretation of clinical results. AB - Some clinical information systems vendors are making significant progress in improving the presentation of integrated clinical information to the physician. Many, however, are emphasizing advanced access and distribution methods, (e.g., Internet) rather than enhancing presentation formats and content. Although we seemingly have the technology tools in hand, and are closer today than ever before, a simple, easy to interpret, user- and context-sensitive presentation of a set of correlated clinical information remains an elusive goal. PMID- 11210211 TI - Technology assessment: measuring the outcomes of laboratory practice. AB - The collision of explosive growth in biomedical technology and pressure to contain cost requires that managers of health-care services base decisions to introduce new technology on hard evidence that the benefits outweigh the costs of the new technology. Outcomes research measures the impact of new technology and changes in clinical practice on patient well-being or financial performance. Outcomes research in the clinical laboratory requires a systematic collection of data that is best accomplished in conjunction with a broader health services research effort that includes a multi-disciplinary team of laboratorians, clinicians, administrators, and statisticians. The major requirement for successful outcomes research is an integrated information system that includes clinical, demographic, administrative, claims, financial, and survey information. PMID- 11210214 TI - Access to medical information: 10 ethical guidelines. PMID- 11210213 TI - Defining/measuring the value of clinical information. AB - Laboratory test results are of limited use in the absence of corresponding clinical information. The range of necessary and pertinent information is broad, but may be as narrow as knowing the patient's age and gender or the site from where a culture specimen was collected, up to the knowledge of the complete clinical history and physical examination for proper interpretation of a test result. Several issues are involved in the utilization of the clinical laboratory from the perspective of clinical appropriateness. In this article, we try to define and elaborate on how critical clinical information is for the pathologists and clinicians alike with the ultimate goal of optimal patient care. PMID- 11210215 TI - The changing role of the medical technologist from technologist to information specialist. AB - Pathology laboratory services are dependent on the laboratory information system (LIS) to organize the work, manage the operation, and communicate the results for effective laboratory medicine. For maximum efficiency, staffing for the LIS should be an integral component of laboratory operations and is facilitated by a two-tier structure. A core LIS staff provides system support and continuous services. A group of bench medical technologists have multitasking responsibilities, including LIS support for a specific laboratory work area. The two components form a team that uses staff efficiently to provide ongoing operational services and flexibility for problem solving and new functionality implementation. PMID- 11210216 TI - The 21st century laboratory: information technology and health care. PMID- 11210217 TI - The electronic medical record: implications for the laboratory. AB - This article describes experiences over the past 5 years with the application of a computerized patient record system and an electronic result inquiry system at Mayo Clinic. These systems now handle 56,000 results and 170,000 inquiries daily- 94% relating to the laboratory. The goal of aligning laboratory services with clinical objectives is outlined with an emphasis on converting data into information and knowledge that can be used to improve patient care. Efficiencies noted thus far include a substantial reduction (68%) in phone inquires after deployment of electronic result inquiry. The electronic medical record has gone from concept to reality. As we transition into this new environment and attempt to fulfill the implicit hopes and promises this tool affords, we would wish to quantify its effect. One department lending itself to enumeration is laboratory services. The perspectives shared are gleaned from the Mayo experience and personal observations of the practice of laboratory medicine elsewhere. PMID- 11210218 TI - Information management: moving from test results to clinical information. PMID- 11210219 TI - Implementation of data security and data privacy provisions will bring sweeping changes to laboratory service providers. AB - The Health Insurance Portability and Accountability Act included substantial changes involving handling of health information by establishing national standards for electronic transactions, data privacy, and data security. The first final rule for electronic transaction standards was published August 17, 2000. The remaining final rules are expected to be published in Winter 2000. Providers, such as clinical laboratories, will have 26 months from the data of publication to comply. The civil monetary fines for noncompliance are substantial. This article will review the key provisions of the data security and data privacy proposed rules. These provisions will touch virtually every aspect of electronic claims submissions, electronic data transactions, and the electronic storage of medical information. The proposed rules will require a coordinated approach by providers to develop the policies and procedures, and the technical and physical infrastructure to protect health information. Moreover, providers will need to identify a privacy officer, to review existing privacy policies to compare the proposed rule with any existing state laws to determine which may be more stringent, and to develop new policies to address the particular requirements of the final rule. PMID- 11210220 TI - Case studies in ethics. Expect the unexpected. PMID- 11210222 TI - Determination of exchangeable protons in natural organic matter using a home-made hydrogen/carbon analyser. AB - A home made hydrogen/carbon analyser was used to determine the portion of exchangeable protons in aquatic humic substances. For this purpose, equal sample amounts were dissolved in H2O and D2O, respectively, dried and combusted in a stream of oxygen. The amount of water resulting from combustion was measured by an infrared detector which recorded the OH bending vibration of H2O. The bands stemming from HOD or D2O were not registered by the detection unit. Thus, combustion of organic samples containing exchangeable protons dissolved in D2O resulted in a significantly smaller signal compared to the signal observed for the same sample dissolved in H2O. The relative intensity loss of the H2O signal observed after combustion was used to derive the portion of exchangeable protons in a standard reference material, a humic substance isolated by the International Humic Substances Society (Suwannee River fulvic acid). According to this method about 20% of the sample protons could be identified as exchangeable protons. With regard to titration data the portion of protons bound to non acidic hydroxy functions could be estimated. The validity of this procedure was proved by combustion experiments using commercially available deuterated substances as well as organic model compounds dissolved in D2O and H2O, respectively. PMID- 11210221 TI - Making choices: to commute or not to commute? PMID- 11210223 TI - Microwave heated vapor-phase digestion method for biological sample materials. AB - A microwave heated, vapor-phase nitric acid-hydrogen peroxide digestion method for pulverized, biological sample materials was developed. Sample masses up to 200 mg were digested using calibrated quartz inserts inside first generation type, low-pressure, Teflon-PFA microwave vessels. In the first step, samples were digested in the vapor-phase for 80 min using a progressive heating pattern. Three mL of 70% nitric acid and 0.5 mL of 30% hydrogen peroxide were used as digestion reagents. In the second step, the small residue left after first step digestion was dissolved in 1.4% nitric acid or additionally with 0.5% hydrofluoric acid by heating for 15 min. The digestion method was optimized using pike (Esox lucius) muscle as a test material. The method was further optimized using three certified reference materials. Ca, Cu, Fe, Mg and Zn were determined from NIST-SRM 1577a bovine liver by ICP-AES. Cr and Ni were determined from NIST-SRM 8433 corn bran and NRCC DOLT-2 dogfish liver by GFAAS. For all elements the values obtained were close or within certified limits. Spike recoveries were between 96 to 107%. Digestion efficiency ranged from 91 to 99%. PMID- 11210224 TI - DNA electrochemical biosensors. AB - Disposable electrochemical DNA-based biosensors are reviewed; they have been used for the determination of low-molecular weight compounds with affinity for nucleic acids and for the detection of the hybridisation reaction. The first application is related to the molecular interaction between surface-linked DNA and the target pollutants or drugs, in order to develop a simple device for rapid screening of toxic or similar compounds. The determination of such compounds was measured by their effect on the oxidation signal of the guanine peak of calf thymus DNA immobilised on the electrode surface and investigated by chronopotentiometric analysis. The DNA biosensor is able to detect known intercalating compounds, such as daunomycin, polychlorinated biphenyls (PCBs), aflatoxin B1, and aromatic amines. Applicability to river and waste water samples is also demonstrated. Disposable electrochemical sensors for the detection of a specific sequence of DNA were realised by immobilising synthetic single-stranded oligonucleotides onto a graphite screen-printed electrode. The probes became hybridised with different concentrations of complementary sequences present in the sample. The hybrids formed on the electrode surface were evaluated by chronopotentiometric analysis using daunomycin as indicator of the hybridisation reaction. The hybridisation was also performed using real samples. Application to apolipoprotein E (ApoE) is described, in this case samples have to be amplified by PCR and then analysed by DNA biosensor. The extension of such procedures to samples of environmental interest or to contamination of food is discussed. PMID- 11210225 TI - Biohybrid microarrays--impedimetric biosensors with 3D in vitro tissues for toxicological and biomedical screening. AB - To investigate the effectiveness of potential anticancer therapeutics or therapies, efficient screening methods are required. On the one hand, multicellular 3D aggregates (spheroids) are a powerful in vitro model for simulating the in vivo situation and on the other hand, planar electrode structures are generally highly suitable for automation and parallel testing. Here, the detection of the effect of active substances on spheroids positioned on electrodes of substrate integrated electrode arrays is exemplarily investigated. As a 3D tissue model a reaggregation system of T47D clone 11 tumor cells is used. The effect of cytotoxins (DMSO, Triton X-100) on spheroids can be detected by recording the effective impedance of planar electrodes covered by spheroids. The equivalent circuit model parameter of electrodes covered by cytotoxin treated spheroids are determined from recorded impedance spectra and compared to the parameter of electrodes covered by control spheroids as well as not covered electrodes. Spheroids on electrodes mainly influence the electrode impedance in the frequency range of 10 kHz to 1 MHz. The results are discussed in view of an optimal electrode/spheroid-interface for sensing the effects of therapeutics with high sensitivity. PMID- 11210226 TI - Multiparametric microsensor chips for screening applications. AB - The identification of drug targets for pharmaceutical screening can be greatly accelerated by gene databases and expression studies. The identification of leading compounds from growing libraries is realized by high throughput screening platforms. Subsequently, for optimization and validation of identified leading compounds studies of their functionality have to be carried out, and just these functionality tests are a limiting factor. A rigorous preselection of identified compounds by in vitro cellular screening is necessary prior to using the drug candidates for the further time consuming and expensive stage, e.g. in animal models. Our efforts are focused to the parallel development, adaptation and integration of different microelectronic sensors into miniaturized biochips for a multiparametric, functional on-line analysis of living cells in physiologically environments. Parallel and on-line acquisition of data related to different cellular targets is required for advanced stages of drug screening and for economizing animal tests. PMID- 11210227 TI - Automatization for development of HPLC methods. AB - Within the frame of inprocess analytics of the synthesis of pharmaceutical drugs a lot of HPLC methods are required for checking the quality of intermediates and drug substances. The methods have to be developed in terms of optimal selectivity and low limit of detection, minimum running time and chromatographic robustness. The goal was to shorten the method development process. Therefore, the screening of stationary phases was automated by means of switching modules equipped with 12 HPLC columns. Mobile phase and temperature could be optimized by using Drylab after evaluating chromatograms of gradient elutions performed automatically. The column switching module was applied for more than three dozens of substances, e.g. steroidal intermediates. Resolution (especially of isomeres), peak shape and number of peaks turned out to be the criteria for selection of the appropriate stationary phase. On the basis of the "best" column the composition of the "best" eluent was usually defined rapidly and with less effort. This approach leads to savings in manpower by more than one third. Overnight, impurity profiles of the intermediates were obtained yielding robust HPLC methods with high selectivity and minimized elution time. PMID- 11210228 TI - Detection of metal ions in aqueous solution by voltohmmetry. AB - A new electrochemical detection principle is described for the trace analysis of dissolved species which can be deposited at polycrystalline thin-film metal electrodes and which change the surface resistance of the electrode. Because the latter parameter is measured in dependence on the applied electrode potential this method is called voltohmmetry. The preparation of the required thin-film electrodes and the experimental set-up is introduced and discussed. Typical voltohmmetric experiments are illustrated by measurements of Tl+/Tl at polycrystalline gold electrodes with a thickness of 15 nm. The analytical capabilities of this new approach are discussed. It is already possible to determine heavy metals such as Tl+, Pb2+ or Cd2+ in the range of a few microgram/L by surface resistance-potential measurements at thin-film electrodes with a simple cyclic technique. Further developments of voltohmmetry are envisaged. PMID- 11210229 TI - Synthesis and application of 4-(N,N-dimethylaminosulfonyl)-7-N-methylhydrazino 2,1,3-benzoxadiazole (MDBDH) as a new derivatizing agent for aldehydes. AB - In a five step synthesis, 4-(N,N-dimethylaminosulfonyl)-7-N-methylhydrazino-2,1,3 benzoxadiazole (MDBDH) was prepared in high yields as a stable new derivatizing agent for carbonyl compounds. Reagent and derivatives have not been described in literature before. Major advantage of this substance compared with similar reagents is its improved solubility in polar solvents, e.g. methanol and ethanol. MDBDH reacts with aldehydes in the presence of an acidic catalyst under formation of the corresponding hydrazones. These are separated by means of reversed-phase liquid chromatography and detected UV/vis spectroscopically at wavelengths around 450 nm, depending on the individual hydrazone. MDBDH reacts with oxidizers as nitrogen dioxide and nitrite to only one product, 4-(N,N-dimethylaminosulfonyl)-7 methylamino-2,1,3-benzoxadiazole (MDBDA), which can easily be separated from the hydrazones of lower aldehydes. Due to large molar absorptivities and absorption maxima at wavelengths > 430 nm, limits of detection range from 4 x 10(-8) to 6 x 10(-8) mol.L-1, and limits of quantification range from 1 x 10(-7) to 2 x 10(-7) mol.L-1 for the individual hydrazones. The method was applied to the determination of aldehydes in automobile exhaust. PMID- 11210230 TI - Fast enantioselective separation of clevidipine and a dihydropyridine substituted acid by SFC on Chiralpak AD. AB - Conditions for the fast separation of the enantiomers of a dihydropyridine substituted acid on a 50 x 4.6 mm ID short Chiralpak AD column with 2-propanol modified carbon dioxide as the mobile phase are presented. A high throughout of samples can be accomplished through the continuous sample loading of the loop of the injector. If a continuous data collection was used 10 separations could be performed in about 5 min with a precision of 0.6% RSD for the area ratio (n = 10). The parent drug clevidipine can also be analyzed and its enantiomeric composition determined after alkaline hydrolysis into its acid, either through hydrolysis followed by extraction to dichloromethane or by direct analysis of the hydrolysis media. About 1 min is required for each run. Using 0.1 M of methanolic sodium hydroxide 2 min are sufficient for the hydrolysis, and, including weighing, only 5 min are required to analyze clevidipine. PMID- 11210231 TI - Automated solid phase dynamic extraction--extraction of organics using a wall coated syringe needle. AB - Extractions of liquid samples were carried out using wall coated needles prepared from stainless steel capillary columns instead of syringe needles. This micro extraction technique was applied to the analysis of pesticides in water. Important parameters influencing the extraction such as sample velocity, extraction time and also the desorption parameters were investigated and optimized. Automation of this technique was realized using a conventional automatic sampler. Limits of detection were improved using the multiple extraction/desorption technique. Chromatographic data and limits of detection were compared with those obtained by solid phase micro extraction (SPME). Using a needle with a 7 microns film yielded limits of detection varying from 0.001-0.1 microgram/L and were in the same range as those resulting from the extraction using a 100 microns polydimethylsiloxane (PDMS) SPME fiber. The main advantages of the needle extraction technique were the significantly higher extraction speed and the practical aspects of a stable steel needle compared to those of a fragile fiber. The extraction speed using a needle with a 7 microns film was up to five times higher than the speed of SPME using a 100 microns PDMS fiber. The steel needle could be stressed mechanically in a higher extent than a SPME fiber. Sample volumes and aliquots of liquid media could be handled and moved from one bottle to another using the automatic sampler. PMID- 11210232 TI - Reference materials service for chemical measurements in Germany. PMID- 11210233 TI - Microwave assisted digestion of atmospheric aerosol samples followed by inductively coupled plasma mass spectrometry determination of trace elements. AB - A microwave digestion method in a closed vessel was developed for the determination of trace metals in atmospheric aerosols using inductively coupled plasma mass spectrometry (ICP-MS). A recovery study for the elements V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Cd, Sb, and Pb was conducted using multi-elemental standard solutions, NIST 1633b Trace Elements in Coal Fly Ash, and NIST 1648 Urban Particulate Matter. A simple digestion method using only HNO3/H2O2 gave good recoveries (90%-108%) for all elements except Cr in SRM 1648, but yielded low recoveries for SRM 1633b. A more robust method using HNO3/H2O2/HF/H3BO3 yielded higher recoveries (82%-103%) for the lighter elements (V-Zn) in SRM 1633b, and improved the Cr recovery in SRM 1648, but decreased the Se recovery in both SRMs. A comparative analysis of aerosol samples obtained at a remote mountain location Nathiagali, Pakistan (2.5 km above mean sea level), and Mayville, New York, downwind from the highly industrialized Midwestern United States, was carried out using Instrumental Neutron Activation Analysis (INAA) for the elements Cr, Mn, Fe, Co, Zn, As, Se, and Sb. The simple digestion method yielded excellent agreement for Cr, Fe, Zn, As, Se, and Sb, with slopes of the ICP-MS vs. INAA regressions of 0.90-1.00 and R2 values of 0.96-1.00. The regressions for Mn and Co had slopes of 0.82 and 0.84 with R2 values of 0.83 and 0.82, respectively. Addition of HF/H3BO3 did not improve the correlation for any of the elements and degraded the precision somewhat. The technique provides sensitivity and accuracy for trace elements in relatively small aerosol samples used in atmospheric chemistry studies related to SO2 oxidation in cloud droplets. The ability to determine concentrations of a very large number of elements from a single analysis will permit source apportionment of various trace pollutants and hence strategies to control the sources of air pollution. This is particularly important as the health effects of particulate matter are increasingly recognized. PMID- 11210234 TI - Extraction and detection of arsenicals in seaweed via accelerated solvent extraction with ion chromatographic separation and ICP-MS detection. AB - An accelerated solvent extraction (ASE) device was evaluated as a semi-automated means of extracting arsenicals from ribbon kelp. The effect of the experimentally controllable ASE parameters (pressure, temperature, static time, and solvent composition) on the extraction efficiencies of arsenicals from seaweed was investigated. The extraction efficiencies for ribbon kelp (approximately 72.6%) using the ASE were fairly independent (< 7%) of pressure, static time and particle size after 3 ASE extraction cycles. The optimum extraction conditions for the ribbon kelp were obtained by using a 3 mL ASE cell, 30/70 (w/w) MeOH/H2O, 500 psi (1 psi = 7 KPa), ambient temperature, 1 min heat step, 1 min static step, 90% vol. flush, and a 120 s purge. Using these conditions, two other seaweed products produced extraction efficiencies of 25.6% and 50.5%. The inorganic species present in the extract represented 62.5% and 27.8% of the extracted arsenic. The speciation results indicated that both seaweed products contained 4 different arsenosugars, DMA (dimethylarsinic acid), and As(V). One seaweed product also contained As(III). Both of these seaweed products contained an arsenosugar whose molecular weight was determined to be 408 and its structure was tentatively identified using ion chromatography-electrospray ionization-mass spectrometry/mass spectrometry (IC-ESI-MS/MS). PMID- 11210235 TI - Determination of elements by nuclear analytical methods. AB - The working principle of nuclear analytical methods (NAMs) is not influenced by the chemical bond. Consequently, they are independent counterparts to the well known chemical procedures. NAMs obey fundamental laws or can be described and understood thoroughly. This qualifies them as candidates for reference methods. Although following similar nuclear reaction schemes, they comprise bulk analyzing capability (neutron and photon activation analysis) as well as detection power in surface near regions of solids (ion beam techniques). Prominent features of NAMs are sensitivity, selectivity, multielement determination and linearity of the calibration function covering a concentration range of several orders of magnitude. Moreover, ion beam techniques allow depth profiling with nm-resolution in several cases while the ion microprobe additionally offers a lateral resolution in the micron-scale. As NAMs require expensive apparatus (nuclear reactor, accelerator in radioactive control areas) their availability is restricted to a small number of suitably equipped institutes. However, they are able to solve complex analytical tasks, take part in key comparisons and play an essential role in the certification of reference materials. PMID- 11210237 TI - Determination of vitamins A and E in milk samples by fluorescence in micellar media. AB - The fat-soluble vitamins A and E in milk samples were determined by fluorescence at room temperature in an aqueous media of micellar solutions. Different types of surfactants were studied; the cationic hexadecyltrimethylammonium bromide (CTAB), the anionic sodium dodecylsulfate (SDS) and the non-ionic polyoxyethylene(23)laurylether (Brij 35). The detection limits ranged between 50 and 90 ng.L-1 for both vitamins in CTAB and Brij 35. The method has been applied to the determination of vitamins A and E in milk samples. PMID- 11210236 TI - Comparative assessment of two sequential chemical extraction schemes for the fractionation of cadmium, chromium, lead and zinc in surface coastal sediments. AB - Two existing sequential chemical extraction schemes, involving respectively five and six leaching steps with solutions of increasing dissolving power, were compared. The methods have been applied to surface sediment samples collected in a marine estuary zone potentially exposed to contamination arising from nearby industrial activities. A certified reference material (MURST-ISS-A1) consisting of an Antarctic bottom sediment for which no information regarding phase dependent concentration is available, was also analyzed. In order to evaluate the partition of metals among different geochemical forms, the concentrations of cadmium, chromium, lead and zinc were measured in the liquid extracts by Zeeman corrected flame atomic absorption and by inductively coupled plasma-atomic emission spectrometry. The total metal concentrations were determined after strong acid attack, and the adequacy of this total digestion/dissolution technique was verified by its application to the reference material. Comparison of total metal concentrations with the sum of concentrations associated with the individual phases was employed to assess possible analyte losses or contaminations. Precisions for both sequential procedures were comparable, but some inconsistencies in mass balances were found in one of the samples for the distribution of Zn in the soluble/exchangeable fractions and for Cd in the bound to carbonates form. In addition, the six steps procedure produced lower concentration values in the case of elements associated to the residual fraction. For the five steps method mass balances showed acceptable agreement, with average recoveries in the 87 to 106% range. On the whole, differences in metal distributions were observed, being more marked for the bottom sediment. Significant proportions of the studied elements, with the exception of Cr, were found as easily extractable forms. X-ray diffraction and petrographic observation of the surface sediments allowed qualitative correlation between the leaching results obtained and the presence of defined geochemical phases. PMID- 11210239 TI - Diabetes and vascular disease. AB - Cardiovascular and cerebrovascular disease are two of the most important causes of morbidity and mortality in the USA and worldwide. The impact of these conditions is even more profound in patients with diabetes. The aims of the Vascular Disease Working Group in the articles that follow are to review the impact of cerebrovascular and cardiovascular disease in the general population, and, specifically, in the patient with diabetes, and to suggest appropriate treatment. Important steps to decreasing the risk of these diseases in diabetic patients are strict glycaemic control, control of hypertension, and modification of dyslipidaemia. PMID- 11210238 TI - Determination of phosphate in urine by sequential injection analysis. AB - Two simple turbidimetric methods for the determination of phosphate in urine are presented and compared. One method is based on the calcium phosphate crystallisation, and the other one on the inhibitory action of phosphate on the calcium carbonate crystallisation. The analytical features of both methods were: linear range = 0.2-1.5 g L-1, LOD = 14 mg L-1 and RSD 1.1-2.0% for the calcium phosphate method, linear range = 0.1-1.8 mg L-1, LOD = 0.01 mg L-1 and RSD 0.97 1.90% for the inhibitory method. Urines with high calcium content (> or = 400 mg L-1) can interfere the method based on the crystallisation of calcium phosphate. This interference was solved using a cation exchange resin as a part of the manifold. Considering the low toxicity of used reagents, these methods can be considered as a contribution to Green Analytical Chemistry. PMID- 11210240 TI - Risk factors for vascular disease in patients with diabetes. AB - The risks of cardiovascular and cerebrovascular disease in patients with diabetes are greater than those in persons without diabetes. This is due, in part, to the metabolic effects of insulin resistance. Other contributing factors include hyperglycaemia, dyslipidaemia, hypertension, hypercoagulability, homocysteinaemia, smoking, and obesity. Risk factor modification, where possible, can reduce the risk of complications of diabetes and macrovascular disease. PMID- 11210241 TI - Pathogenesis of vascular disease. AB - Only recently are we beginning to understand the complex interplay of factors involved in vascular disease and diabetes. Insulin resistance provides a starting point to explain the many factors that lead to the more severe vascular disease characteristic of diabetes. Insulin resistance syndrome comprises insulin resistance and compensatory hyperinsulinaemia as well as hypertension, dyslipidaemia, macrovascular disease, and increased plasminogen activator inhibitor-1 activity. The development of type 2 diabetes may be viewed as the inability of the pancreas to continue to overcome insulin resistance, even with excessive insulin production. PMID- 11210242 TI - Vascular disease prevention in patients with diabetes. AB - Prevention is the key to reducing the vascular sequelae of diabetes. Prevention starts with good glycaemic control and continues with a comprehensive programme of risk modification, such as lipid-lowering therapy, antihypertensive treatment, and improved lifestyle. With regard to lipid modification, agents such as statins may provide additional, non-lipid effects in both the diabetic and non-diabetic patient. This review discusses recent studies supporting risk reduction, available treatments, and recommendations applicable to the diabetic patient. PMID- 11210243 TI - The impact of cerebrovascular disease. AB - Stroke may be affected by pathologic conditions such as atherosclerosis, vascular injury, coagulopathy, and increased platelet aggregability. Knowledge of the pathophysiology of stroke is critical in order to effectively prevent or treat this disabling state. Cerebrovascular disease is the third leading cause of death in the USA. It is also associated with significant morbidity, leading to extremely high health care costs and lost productivity. Total estimated costs of stroke are estimated to be more than $45 billion annually. This is an especially important issue for patients with diabetes, who are at higher risk for stroke and have a worse clinical outcome than non-diabetic patients. This review describes the impact of vascular disease, particularly cerebrovascular disease, and describes the pathophysiology of the disease. Interventions that result in reduction of stroke will likely result in decreased health care costs and improved clinical outcomes. PMID- 11210244 TI - Attachment of human gingival fibroblasts to periodontally involved root surface following scaling and/or etching procedures: a scanning electron microscopy study. AB - This study evaluated, in vitro, fibroblast attachment to periodontally involved root surfaces which were either root planed or acid/chelated by different agents. Specimens were divided into 3 groups of 12 specimens each. The root surfaces were root planed with a Gracey 7/8 curette, an EMS or an Amdent piezo-electric scaler and treated with saline, citric acid, tetracycline hydrochloride or EDTA to produce different surface textures. They were then cultured with fibroblasts for 72 h and examined by scanning electron microscopy. There was a significantly greater number of fibroblasts attached to specimens treated with citric acid, tetracycline and EDTA than to those root planed only. Furthermore, fibroblasts were more likely to attach to rough-surfaced than to smooth-surfaced specimens. PMID- 11210245 TI - Relationship between the presence or absence of gingival bleeding and the enzymatic BANA test. AB - When periodontal disease started to be considered a bacterial infection mainly mediated by subgingival plaque, the basic problem faced by periodontists was the identification and/or quantification of periodontopathogenic bacteria. However, clinical methods continue to be of great value for the diagnosis of periodontal disease. In the present study we show a significant correlation between an index widely used in clinical practice, the Gingival Index of Loe (1967), based on the presence or absence of bleeding on probing, and the methodology of the BANA test for the detection of the specific enzymatic activity of microorganisms involved in periodontal disease. More sensitive and specific clinical parameters, taken together with other microbiologic methods, will be useful in daily clinical practice even before periodontal treatment. PMID- 11210246 TI - Evaluation of Er:YAG laser and EDTAC on dentin adhesion of six endodontic sealers. AB - The effect of Er:YAG laser application and EDTAC on the adhesion of epoxy resin based endodontic sealers to human dentin was evaluated in vitro. A total of 99 extracted human maxillary molars with their crowns worn flat were used. The teeth were divided into 3 groups: group 1, the dentin surface received no treatment; group 2, EDTAC was applied to the dentin surface for 5 min; group 3, the dentin surface received Er:YAG laser application (2.25 W potency; 11 mm focal distance; 4 Hz frequency; 200 mJ energy; 62 J total energy; 313 mean impulse). Three teeth from each group were analyzed by scanning electron microscopy for changes in dentin surface. The epoxy resin root canal sealers used were: AH Plus, Topseal, Sealer 26, AH 26, and Sealer Plus. The zinc oxide eugenol-based sealer Fillcanal was used as control. Adhesion was measured with a Universal testing machine. The results showed a statistically significant difference at the level of 1% among the dentin treatments. The dentin treated with Er:YAG laser showed greater adhesion with the sealers than dentin treated with EDTAC which was greater than dentin that received no treatment. The Tukey test showed the formation of 5 groups in decreasing order of adhesion: AH Plus, Topseal and Sealer 26, AH 26, Sealer Plus, and Fillcanal (Grossman cement). PMID- 11210247 TI - Reaction of rat connective tissue to implanted dentin tube filled with mineral trioxide aggregate, Portland cement or calcium hydroxide. AB - The subject of this study was to observe the rat subcutaneous connective tissue reaction to implanted dentin tubes filled with mineral trioxide aggregate, Portland cement or calcium hydroxide. The animals were sacrificed after 7 or 30 days and the undecalcified specimens were prepared for histological analysis with polarized light and Von Kossa technique for mineralized tissues. The results were similar for the studied materials. At the tube openings, there were Von Kossa positive granules that were birefringent to polarized light. Next to these granulations, there was an irregular tissue like a bridge that was Von Kossa positive. The dentin walls of the tubes exhibited in the tubules a structure highly birefringent to polarized light, usually like a layer and at different depths. The mechanism of action of the studied materials has some similarity. PMID- 11210248 TI - Microhardness of Nd:YAG laser irradiated enamel surfaces. AB - Several studies have been conducted in order to verify effects of laser irradiation on dental structures. However, different settings and methods employed have led to inconclusive results. The aim of this study was to evaluate the effects of several settings of Nd:YAG laser irradiation on enamel microhardness. Fifteen groups of 10 human third molars each were submitted to Vickers microhardness indentations prior to and after laser irradiation. The data were submitted to the t-test for dependent samples (P < 0.05) for statistical evaluation. Lower total delivered energy (under 30 J) resulted in no statistically significant difference of microhardness between irradiated and non irradiated samples, whereas higher energy settings decreased enamel surface microhardness significantly. This can be due to the significant temperature rise during irradiation. Thus, we conclude that laser irradiation, under the conditions of this study, is not suitable for improving enamel properties, because of decreased microhardness of irradiated samples. PMID- 11210249 TI - Microhardness of enamel restored with fluoride and non-fluoride releasing dental materials. AB - Demineralization caused by frequent ion loss can be detected by a decrease in enamel microhardness. The purpose of this study was to determine the microhardness of the enamel adjacent to restorations with fluoride and non fluoride dental materials after demineralization and remineralization treatments using crowns of 6 recently extracted unerupted third molars which were sectioned into 4 parts. Five penetrations were made in the enamel of the control group and in the enamel adjacent to restorations made with Vitremer, Heliomolar or Z100, to obtain the Knoop microhardness. There was no significant statistical difference between the microhardness of the enamel of the control group and the enamel adjacent to the restorations made with Vitremer and Heliomolar (p < 0.01), nor between the enamel adjacent to the Heliomolar and Z100 restorations. However, there was a statistically significant difference when the Z100 group was compared to the control group and to the Vitremer group. The results point out that some phenomena occurred which interferred with the ionic loss and, consequently, the microhardness of the enamel of the Vitremer and Heliomolar groups, because it was not possible to observe any difference between the microhardness of the enamel of the control group and the groups restored with Vitremer and Heliomolar. PMID- 11210250 TI - Modeling capacity of ENDOflash files in simulated root canals. AB - With the development of rotary nickel-titanium files and their applications in Endodontics, the concepts of root canal preparation have changed. The objective of this research is to evaluate the transportation of simulated root canals caused by stainless steel ENDOflash rotary files compared to nickel-titanium ProFile files (.04, .06 and Orifice Shapers). Twenty-four simulated root canals with a 30 degrees curvature were randomly divided into 2 groups and prepared with ENDOflash or ProFile files according to manufacturers' instructions. Comparison between the simulated root canals before and after instrumentation showed significant differences (p < 0.001) between the groups, with greater transportation observed with ENDOflash files. One case of deformation was observed with a ProFile instrument (#20/.04) and there were no fractures. PMID- 11210252 TI - Compliance with supportive periodontal therapy. Part II: Risk of non-compliance in a 10-year period. AB - Supportive periodontal therapy (SPT) is needed for the success of periodontal therapy; however, patient compliance is poor. Part II of this study analyzes compliance during a 10-year period in an attempt to identify the profile of patients with a higher risk of becoming non-compliant. Data from the records of 874 patients from a private periodontal clinic who had completed active periodontal treatment up to 10 years before and had begun supportive periodontal therapy were analyzed for risk of non-compliance and compliance. The factors evaluated were gender (326 males and 548 females), type of therapy (surgical or non-surgical) and age (< or = 30 years, 31 to 40, 41 to 50, and > or = 51 years old) and the association amongst them. In the period studied, compliance with SPT was 45.8%. Forty-three percent of males and 47% of females discontinued SPT. In the surgical group 43.9% were non-compliant and in the non-surgical group 53.2% were non-compliant. Fifty-nine percent of the patients < or = 30 years of age were also non-compliant. Female patients < or = 30 years and > or = 51 years of age that underwent non-surgical therapy were found to be of higher risk for non compliance in the 10-year period studied. PMID- 11210251 TI - Compressive strength of interocclusal recording materials. AB - Many materials are used for making interocclusal records to mount casts on dental articulators. The strength of these materials during the compressive forces encountered in the mounting process is important because any deformation will cause incorrect occlusal relationships. This investigation compared the deformation of 4 thicknesses (2 mm, 5 mm, 10 mm, 20 mm), when subjected to 25 N compressive force, of 3 interocclusal recording materials: condensation silicone, recording wax, and rubber-based polyvinylsiloxane. Significant differences were recorded for all materials of 20 mm, 10 mm and 2 mm thickness. However, there was no significant difference among the 5 mm groups. Interocclusal records should be made of a minimal thickness, using a recording material which exhibits minimal distortion during compression. PMID- 11210253 TI - Changes in periodontal conditions of children and adolescents from Araraquara, Brazil: 1995-1998. AB - The aim of this study was to compare the periodontal conditions in 7-15-year-olds from Araraquara, SP, Brazil in 1998 with data from 1995. A systematic random sample was drawn from the population of children and adolescents enrolled in all public schools in 1998. The survey was conducted by trained examiners using the CPITN and WHO diagnostic criteria. Results showed an increase in the percentage of students of all ages with healthy periodontal conditions (from 14% in 1995 to 33% in 1998; p < 0.01). An increase in the mean number of healthy sextants (from 3.2 to 4.4; p < 0.0001), a decrease in the mean number of bleeding sextants (from 2.5 to 1.2; p < 0.0001) and no difference in the mean number of sextants with calculus were also observed. At the age of 15, 54% of the students had 5-6 healthy sextants in 1998 compared to 19% in 1995 (p < 0.01). Despite the improvement observed in the periodontal conditions, efforts must be increased in order to achieve the WHO goal for the year 2010 of no more than one sextant affected by bleeding or calculus at the age of 15. PMID- 11210254 TI - Oral squamous cell carcinoma: a retrospective study of 740 cases in a Brazilian population. AB - The purpose of this study was to evaluate, retrospectively, the profile of patients with oral squamous cell carcinoma. They were referred to two hospitals of Belo Horizonte (MG, Brazil) between 1986 and 1996. The medical records of 740 patients presenting oral squamous cell carcinoma were reviewed in detail. The TNM classification and staging, age, gender, race, occupation, and site of the primary tumor were recorded. The male-to-female ratio was 4.8:1. The mean age was 58.6 years. Most of the patients were in their sixties and were farm workers. The tumors were found principally on the tongue. There was a close relationship between some habits (tobacco and alcohol consumption) and the development of oral squamous cell carcinoma. Most of the patients sought medical care in the first year, even though almost half of them had lesions in stage T4. The identification of the characteristics of this specific population might reflect either accomplishments or problems in oral cancer control and can enable the development of a primary prevention program for oral squamous cell carcinoma. PMID- 11210255 TI - Gingival erosive lichen planus: case report. AB - A case of gingival erosive lichen planus is presented with special emphasis on its clinical and microscopic characteristics. The differential diagnosis and the controversy associated with the malignant potential of oral lichen planus is also discussed. PMID- 11210256 TI - Odontoma-producing intraosseous calcifying odontogenic cyst: case report. AB - The present report describes a case of odontoma-producing intraosseous calcifying odontogenic cyst in a 36-year-old Black male in the right mandibular bicuspid region. The lesion involved an unerupted permanent canine, which was displaced to the mandible base and a calcified mass that was later recognized as an odontoma. The lesion was surgically removed. PMID- 11210257 TI - Hydroxylapatite implants with or without collagen in the zygomatic arch of rats. Histological study. AB - The authors studied the behavior of calcium phosphate materials used as inlay implants into bone cavities prepared in the zygomatic arch of rats. Fifty male albino rats were divided into four groups as follows: group I-preparation of bone cavities which did not receive any implant material as controls; group II implants of Interpore 200; group III-implants of experimental hydroxylapatite; group IV-implants of experimental hydroxylapatite combined with collagen. The animals were sacrificed after 5, 15, 30, 60 and 120 days and the specimens were submitted to histological analysis. Results showed that the experimental hydroxylapatite used in group III presented better osteogenic properties compared to the other materials. All tested materials were biocompatible, although group IV presented a more intense inflammatory response. PMID- 11210258 TI - AgNORs in hyperplasia, papilloma and oral squamous cell carcinoma. AB - Ten inflammatory fibrous hyperplasias, ten papillomas, and nineteen oral squamous cell carcinomas were analyzed by the AgNOR technique to determine if different disturbances of oral epithelia presented different AgNOR counts. The papilloma group showed higher mean AgNOR counts (3.15 +/- 0.58) than the hyperplasia group (1.98 +/- 0.24) and smaller than the well-differentiated oral squamous cell carcinoma group (6.56 +/- 1.25) and poorly differentiated oral squamous cell carcinoma group (7.07 +/- 1.60). The differences among the groups of lesions were statistically significant (P < 0.05) except between the well differentiated oral squamous cell carcinoma group and the poorly differentiated oral squamous cell carcinoma group. Our findings suggest that the cellular proliferation ratio in papillomas is greater than hyperplasias and smaller than carcinomas. PMID- 11210259 TI - Comparative study of two digital radiographic storage phosphor systems. AB - The objective of this study was to evaluate the image quality and dynamic range of two digital radiographic storage phosphor systems: Digora (Soredex, Finland) and DenOptix (Gendex, USA). Four objects were analyzed and eight exposure times employed, totaling 64 images that were analyzed by 5 examiners using a scale from 1 to 4 to classify the images. The scores were submitted to analysis of variance and the results showed statistical differences among the averages attributed to the systems, to the exposition times and to the objects (p 0.01 Pound). Digora presented a larger dynamic range and, in general, a better image quality. Although these 2 systems present the same photon detector, they present different results in relation to the evaluated items. PMID- 11210260 TI - Epithelial alterations of secondary palate formation. AB - This study was undertaken to examine the normal and abnormal epithelial alterations of secondary palate in rats. Control and dexamethasone-treated embryos and fetuses of Wistar rats were evaluated by macroscopic and scanning electron microscopic analysis prior to, during, and after fusion of palatal processes. Normal alterations of the surface topography included growth and disorganization of medial edge epithelial cells followed by fusion and posterior migration to both the oral and nasal aspects of the palate. No evidence of epithelial cell death or transformation was observed. Dexamethasone-treated fetuses showed epithelial cells increased in size with a large amount of desquamation, followed by deposition of a disorganized cell layer with keratin like characteristics. This allowed no fusion of palatal processes. PMID- 11210261 TI - The facilitating role of mobile dental van programs in promoting professional dental education. AB - The main goal of the University of Texas Health Science Center (UTHSCSA) dental van programs is to provide training in delivering care to diverse segments of the population. The UTHSCSA is the Academic Health Center for all of South Texas, a region with 25% of the State's population and 60% Hispanic. About 60% of the region's counties are federally designated dental health personnel shortage areas. Interdepartmental efforts with the participation of dental hygiene, community dentistry, oral diagnosis, periodontics and general practice carried out two programs during the 1994-95 academic year. At the Saint Philip of Jesus Clinic, a charity clinic, and at the Willows Development Center for Severely and Profoundly Mentally Retarded, the dental van was used to provide preventive and restorative care. A questionnaire to measure the value of the programs indicated that students perceived them as important educational activities which increased their confidence in treating persons in the community, especially persons with disabilities. Program output was quantitatively assessed. An average of 8 preventive procedures, 7 fillings, 2 sealants and 1 extraction or referral were provided each working day. Eighty patients were seen at the Saint Philip Clinic (2.5 visits per patient) and 130 patients were seen at the Willows Development Center. Overall, 80 students and 6 faculty participated in providing screening, treatment and referral services. Dental van programs promote access to dental care and increase the visibility of dental schools within the university and community. Current tendencies to halt new program initiatives and phase out existing programs due to shifting financial priorities should be carefully considered in view of the 1995 Institute of Medicine (IOM) report on the future of dental education. PMID- 11210262 TI - Clinical and histological evaluation of granuloma gravidarum: case report. AB - Granuloma gravidarum is a benign lesion of the oral mucosa which occurs during pregnancy. This case report presents the clinical and histological evaluation and treatment of a granuloma gravidarum in a patient in the 9th month of pregnancy. PMID- 11210263 TI - Maxillary lateral incisor with two root canals: fusion, gemination or dens invaginatus? AB - Endodontic retreatment of a maxillary right lateral incisor with two root canals is described. The diagnosis of fusion, gemination or dens invaginatus could not be made, due to conflicting findings, and to previous root canal treatment that erased the original configuration of the pulp chamber. PMID- 11210264 TI - Craniometaphyseal dysplasia: case report. AB - Craniometaphyseal dysplasia is a rare genetic bone remodeling disorder characterized by undertubulation of the long bones, especially in the lower extremities, causing deformities of the metaphyses of the long bones, and sclerosis of the skull base or cranial bone hyperostosis. The authors report a case of craniometaphyseal dysplasia in an 8-year-old Brazilian child, emphasizing the importance of precocious diagnosis of this rare genetic disorder. PMID- 11210265 TI - A rare case of lip ulcer infected by Klebsiella pneumoniae: case report. AB - The aetiology of mouth ulcers is diverse and may include several types of trauma, systemic disease and infection. The size, depth, outline, base, aspect of the floor, pain, time of evolution and resolution of oral ulcers are discussed. Both past and present medical history, biopsy, blood tests and microbiological tests are also considered in order to assure precise identification. This paper reports a case of a lip ulcer caused by Klebsiella pneumoniae. PMID- 11210266 TI - In vitro study of the effect of aged eugenol on the flow, setting time and adhesion of Grossman root canal sealer. AB - In the present study, the effect of aged eugenol (up to 180 days) on the flow, setting time and adhesion of Grossman root canal sealer was evaluated, following the American Dental Association specification number 57 for root canal sealers. An Instron Universal testing machine 4444 was used for testing adhesion. There were statistically significant differences between groups, with a higher flow, lower setting time and adhesion for aged eugenol. It can be concluded that time affects eugenol, with consequent effects on Grossman sealer. PMID- 11210267 TI - Homogenous implant in rat tibias of matrix preserved in 98% glycerin: histomorphologic study. AB - As a chemical medium for preservation of tissues, glycerin has shown good results because it maintains the cellular integrity despite the tissue dehydration it causes. Taking advantage of the osteoinducing properties of the osseous matrix and glycerin as a proper medium for tissue preservation, osseous matrix was implanted in rat tibias. Twenty-four rats were used, each receiving two surgical wounds. In one of the wounds an osseous matrix preserved in 98% glycerin was implanted and the other received a matrix without preservatives. Six animals were sacrificed on days 10, 20, 30 and 60 post-implant. After routine histological processing, the specimens were stained in hematoxylin-eosin and Masson's trichrome. The results showed that the matrixes preserved in glycerin presented faster resorption with replacement by newly formed tissue. PMID- 11210268 TI - Fluoride release and uptake from glass ionomer cements and composite resins. AB - The aim of this investigation was to evaluate fluoride release and uptake from 4 glass ionomer cements (GICs)--Vitremer (VIT), Fuji II LC (FII LC), Fuji IX (FIX), Chelon Fill (CHE)--and 2 composite resins (CRs)--Heliomolar (H) and Zeta-100 (Z 100). Eight discs (8 mm x 2 mm) were made of each material and were stored in plastic vials containing artificial saliva at 37 degrees C. In group 1 (N = 3), the specimens were immersed in artificial saliva which was changed daily for 25 days. In group 2 (N = 5), besides receiving the same treatment as group 1, the specimens were immersed, after 24 hours, in a fluoride solution (1% NaF) for 1 min before daily saliva change. An ion-specific electrode (9609 BN-Orion) connected to an ion analyzer (SA-720 Procyon) was used to determine the amount of fluoride released at days 1, 2, 5, 10, 15, 20 and 25. Data were analyzed using two way ANOVA and Friedman's test. GICs released more fluoride during the first day and after this period the mean fluoride released decreased. Composite resin H released fluoride during the first day only and Z-100 did not release fluoride. In terms of NaF treatment, CRs did not show fluoride uptake, whereas the GICs showed fluoride uptake (VIT = FII LC = CHE > FIX). PMID- 11210269 TI - Capacity of denture plaque/biofilm removal and antimicrobial action of a new denture paste. AB - The efficacy of a paste for complete dentures was analyzed in terms of denture plaque/biofilm removal and antimicrobial action against specific microorganisms by determination of colony forming units of mutans group streptococci and yeast from 120 full denture wearers with a healthy palatine mucosa. The patients were given a questionnaire to evaluate the experimental product in terms of important characteristics. The paste was widely accepted by the patients, and effective in denture plaque removal and antimicrobial action. The species of yeasts most frequently isolated were C. albicans, C. tropicalis and C. glabrata. We conclude that it is possible for complete denture wearers to keep their dentures clean with the regular use of a paste-like hygienic product. PMID- 11210270 TI - The influence of five impression techniques on the dimensional accuracy of master models. AB - A high-grade steel model with different preparation angles of 3 degrees, 7 degrees and 11 degrees in one- and two-step impression techniques were made for the determination of the influence of the preparation angle on the dimension loyalty of the resulting master casts. Using a 3-D-measuring instrument, analysis of the data showed that with the correction technique the model abutments led to a reduction in dependency on the preparation angle. The general reduction in stump height of the abutments was independent of the preparation angle. The double-mix technique showed decent increased abutments and is thus recommended for impressions of supragingival preparations. PMID- 11210271 TI - Effect of saccharin on antibacterial activity of chlorhexidine gel. AB - Although chlorhexidine is the most effective agent against dental plaque it is extremely bitter. To prepare formulations, it is necessary to use flavoring and sweetening, which can inhibit the antibacterial effect of chlorhexidine. Saccharin has been considered a compatible substance to use in chlorhexidine rinse or gel preparations; however, the effect of a range of concentrations has not been studied. To evaluate the effect of different concentrations of saccharin on the antibacterial activity of chlorhexidine gel, hydroxy-ethyl-cellulose gels containing 1.0% chlorhexidine digluconate and 0.0 to 1.0% sodium saccharin were prepared. Activity against Streptococcus mutans was evaluated using the agar diffusion method and determination of MIC values. The inhibitory zones of growth were 7.83 +/- 0.54 mm when no saccharin was added to the chlorhexidine gel and 7.75 +/- 0.50, 7.63 +/- 0.48, 6.21 +/- 0.40, 4.13 +/- 0.38, when the concentrations of saccharin in the gels were 0.02, 0.10, 0.5, and 1.0%, respectively. The range of MIC values was 1-2 micrograms/ml, with saccharin concentrations of 0%, 0.02, and 0.1%. In contrast, the MIC values were 4-8 and 8 16 micrograms/ml with saccharin concentrations of 0.5% and 1.0%, respectively. The paired "t" test showed that 0.5 and 1.0% sodium saccharin inhibit the antibacterial activity of 1% digluconate chlorhexidine gel. These in vitro results suggest that saccharin may inhibit the efficacy of chlorhexidine against mutans streptococci, depending on the concentration. PMID- 11210273 TI - Cephalometric evaluation of patients with anterior open-bite. AB - Cephalometric evaluations of the skeletal pattern of 30 patients with anterior open-bite malocclusion were compared to those of 30 individuals with a normal overbite. The posterior/anterior face height ratio (PFH/AFH) was the only skeletal characteristic statistically different in the two groups. The other cephalometric measurements were not found to be statistically different in the malocclusion and normal overbite groups (SN-GoGn, SN-PP, gonial angle, LFH/AFH ratio), indicating that there is no skeletal origin in the group with anterior open-bite in this study. PMID- 11210272 TI - Antimicrobial and chemical study of MTA, Portland cement, calcium hydroxide paste, Sealapex and Dycal. AB - The objective of this study was to investigate the antimicrobial action of mineral trioxide aggregate (MTA), Portland cement, calcium hydroxide paste (CHP), Sealapex and Dycal. The chemical elements of MTA and two Portland cements were also analyzed. Four standard bacterial strains: Staphylococcus aureus (ATCC 6538), Enterococcus faecalis (ATCC 29212), Pseudomonas aeruginosa (ATCC 27853), Bacillus subtilis (ATCC 6633), one wild fungus, Candida albicans (ICB/USP-562), and one mixture of these were used. Thirty Petri plates with 20 ml of BHI agar were inoculated with 0.1 ml of the experimental suspensions. Three cavities, each one measuring 4 mm in depth and 4 mm in diameter, were made in each agar plate using a copper coil and then completely filled with the product to be tested. The plates were pre-incubated for 1 h at environmental temperature followed by incubation at 37 degrees C for 48 h. The diameters of the zones of microbial inhibition were then measured. Samples from diffusion and inhibition halos were extracted from each plate and immersed in 7 ml BHI broth and incubated at 37 degrees C for 48 h. Analyses of chemical elements present in MTA and in two samples of Portland cement were performed with a fluorescence spectrometer Rx. The results showed that the antimicrobial activity of CHP was superior to those of MTA, Portland cement, Sealapex and Dycal, for all microorganisms tested, presenting inhibition zones of 6-9.5 mm and diffusion zones of 10-18 mm. MTA, Portland cement, and Sealapex presented only diffusion zones and among these, Sealapex produced the largest zone. Dycal did not show inhibition or diffusion zones. Portland cements contain the same chemical elements as MTA except that MTA also contains bismuth. PMID- 11210274 TI - Risk indicators for periodontal diseases in Guatemalan adolescents. AB - A random sample of sixty-two 11-15-year-old adolescents from 17 different locations in Guatemala were selected for this study. Pocket depth, Plaque Index, and bleeding upon probing were recorded from 6 randomly selected sites in each subject (a total of 372 sites). Subgingival plaque samples were subsequently collected from these sites and processed by several assays. For cost reasons, in each pair of sites different assays were performed as follows: sites #1, #2--BANA test for T. denticola, P. gingivalis, B. forsythus and screening of plaque samples with polyclonal antibodies (ELISA system) for A. actinomycetemcomitans; sites #3, #4--detection of yeasts by SAB agar; sites #5, #6--detection of Entamoeba gingivalis by the Heidenhain iron hematoxylin modified technique. A total of 66% of the children had at least one site that bled upon probing, 42% exhibited at least one site with pocket depth > 3 mm, and 79% exhibited a high Plaque Index, with the percent of sites affected being 30%, 12% and 41%, respectively. In sites #1, #2 (N = 124), the BANA test assay and A. actinomycetemcomitans tested positive in 77% and 47% of the children accounting for 59% and 31% of the sites, respectively. In sites #3, #4 (N = 124), yeasts were detected in 43% of the children and 29% of the sites. In sites #5, #6 (N = 124), Entamoeba gingivalis was detected in 21% of the children and in 11% of the sites. The risk for severe gingival inflammation and/or increased probing depth was 1.5 and 5.2 times higher if a positive BANA test or A. actinomycetemcomitans test was found in a particular site. No associations could be found for yeasts and Entamoeba gingivalis. PMID- 11210275 TI - Periodontal disease associated with Langerhans' cell histiocytosis: case report. AB - A clinical case of Langerhans' cell histiocytosis, type eosinophilic granuloma, in a young adult patient is presented. Because of the occurrence of oral manifestations in initial stages of the disease, there is a need for a differential diagnosis, especially with the early-onset periodontitis. PMID- 11210276 TI - Assisting women to establish breastfeeding: exploring midwives' practices. AB - Breastfeeding is recognised by many mothers, families and health professionals to be important for the health and wellbeing of mothers and babies. Successful breastfeeding depends on the acquisition of basic skills, accurate information and practice, and is strongly influenced by the support provided following childbirth. Midwives' practices may therefore have the potential to influence breastfeeding outcomes. Correct positioning and attachment of the newborn at the breast is a crucial component of the successful establishment of breastfeeding. A literature review revealed that minimal research exists on the practices that midwives use when assisting women to initiate breastfeeding. A series of focus group interviews were therefore conducted to stimulate in-depth exploration of midwives' understanding and practices in the positioning and attachment of a newborn infant at the breast. Eighteen midwives, each of whom had worked at least 12 months in the postnatal environment of a large metropolitan hospital in Adelaide, participated in the focus group discussions. Using thematic analysis, the following broad themes emerged from discussions--education, problem-solving, support, midwives' views about breastfeeding and influences on midwives' practice. These themes identify the roles and practices that midwives take on when assisting women to establish breastfeeding following childbirth, and also raise awareness of influences on their practice. PMID- 11210277 TI - Long-term expressing of breastmilk. AB - This article focuses on the breastfeeding experience of a midwife after the birth of her first child. He was born with a bilateral cleft lip and palate and despite attempting to breastfeed it was not possible physiologically. The decision was made to express breastmilk long-term and feed the baby by Chu Chu teat and squeeze bottle. This article describes the hints and ideas found along the way to make long-term expressing of breastmilk easier. It comes from personal experience, literature and asking other women in similar situations how they managed. PMID- 11210278 TI - Rates of breastfeeding in Australia by state and socioeconomic status: evidence from the 1995 National Health Survey. AB - OBJECTIVE: To estimate rates of breastfeeding in the first year of life in Australia, according to state and socioeconomic status. METHODOLOGY: Analysis of data from the 1995 Australian National Health Survey. RESULTS: Estimated breastfeeding rates are 81.8% on discharge from hospital, 57.1% fully breastfed at three months and 62.6% fully or partially breastfed at three months. At six months, it is estimated that 18.6% of babies are fully breastfed and 46.2% fully or partially breastfed. At one year, 21.2% of infants are receiving some breastmilk. Comparison between states demonstrates that there is considerable variation in breastfeeding practice within Australia. Rates of breastfeeding also vary according to the socioeconomic status of the geographic area in which the child is living, with a strong inverse relationship between rates of breastfeeding and socioeconomic status. CONCLUSION: Australia's target for breastfeeding in the year 2000 is to have 80% of babies at least partially breastfed for the first six months of life. Although Australia has good rates of initiation of breastfeeding these levels are not maintained over time, and it seems unlikely that we will reach the year 2000 targets. PMID- 11210279 TI - Breastfeeding attachment hands-off technique competency checklist. PMID- 11210280 TI - Does maternal obesity adversely affect breastfeeding initiation and duration? AB - OBJECTIVE: To examine the relationship between maternal obesity and the initiation and duration of breastfeeding. METHODS: Analysis was made of the 1995 National Health Survey, in which personal interviews were conducted on a multistage area sample of private dwellings and a list sample of non-private dwellings in all States and Territories of Australia. Mothers between the ages of 17 and 50 years (n = 1991) with children under the age of four years in 1995 participated in the study. RESULTS: Of the group of mothers with a body mass index (BMI) of 20-25, 89.2% (95% confidence interval (CI) 87.4-91.0) initiated breastfeeding, compared with 82.3% (95% CI 77.6-87.0) of mothers with a BMI of 30 or more. There was also a significant difference between the mean and median duration of breastfeeding of obese and non-obese mothers (BMI 30 and over, < 25, respectively). These differences remained significant when maternal smoking, age and other sociodemographic factors were taken into consideration. CONCLUSIONS: Health professionals should be aware that obese women may be at increased risk of not breastfeeding or stopping breastfeeding prematurely. PMID- 11210281 TI - Support for breastfeeding in the first postpartum month: perceptions of breastfeeding women. AB - Support for breastfeeding, particularly in the early weeks, remains a challenge for health professionals. Focus group interviews with South Australian metropolitan mothers about their first month postpartum explored perceptions of available breastfeeding support. Women discussed breastfeeding support as related to place, people and timing. Findings of this retrospective qualitative study indicate that breastfeeding women perceived midwives as unable to provide the support and relationship they needed due to limitations of time and inconsistent rosters of staff. Additionally, confusion was reported to arise from conflicting advice given by midwives. The issues raised by participants provide an opportunity for midwives to consider reshaping their practices to meet the perceived needs of breastfeeding women in the early postpartum period. PMID- 11210282 TI - Meperidine: second-line agent with first-line prescribing practices. AB - Results from this survey need to be viewed within the context of the small number of responses (20%), which may not fully represent the knowledge base of all house officers. Recommendations established by the Agency for Health Care Policy and Research (AHCPR) define standards of care for acute and chronic pain management and address many of the problems seen nationally with meperidine and its metabolite, normeperidine. Data from this survey have assisted us in providing educational programs which are in line with these guidelines for house officers. PMID- 11210284 TI - The febrile traveler. PMID- 11210283 TI - Gilles de la Tourette's syndrome: "merde and foutu cochon". PMID- 11210286 TI - Better than medicine. PMID- 11210285 TI - Bilateral cystic ovarian teratomas. PMID- 11210287 TI - Garlic: the panacea with bad breath. PMID- 11210288 TI - Preconceptual folic acid: opportunity for preconceptual counseling offers opportunity to help prevent neural tube defects. PMID- 11210289 TI - An overview of HCFA's acute myocardial infarction national project. PMID- 11210290 TI - Invasive disease attributed to Streptococcus pneumoniae, 1998-1999. PMID- 11210291 TI - Tobacco control report card: Rhode Island, 2000. PMID- 11210292 TI - Mammographic screening--a review. PMID- 11210293 TI - Who's the criminal? PMID- 11210294 TI - A managed care contract check-list. PMID- 11210295 TI - Treating the many to benefit the few: the modest reach of preventative medications. PMID- 11210296 TI - Clinical management of psoriasis: principles and practice. AB - A chronic condition that compromises many patients' quality of life, psoriasis is treatable with a range of agents, either alone or in combination. Clinical management strategies using these therapies can be organized as a stepped-care approach. For mild disease, corticosteroids and other topical therapies (step 1) are often appropriate. When lesions are more pronounced or extensive, phototherapy (step 2) is often the treatment of choice, and topical treatments or the step 3 agent acitretin can be added to enhance or accelerate therapeutic responses. Step 3 agents, which also include cyclosporine and methotrexate, may be contemplated when psoriasis is moderate or severe. Acitretin may cause acute adverse effects, including mucocutaneous effects, which can be avoided by reducing dosage. Methotrexate treatment can lead to bone marrow suppression and hepatotoxicity, and cyclosporine can cause nephrotoxicity. The clinical uses of these agents are illustrated in part through case presentations drawn from the authors' practices, and the supportive role of the National Psoriasis Foundation is reviewed. PMID- 11210297 TI - [Macrolide antibiotic clarithromycin (Klabax) in treatment of community-acquired respiratory tract infections]. PMID- 11210299 TI - [Pathogens in community-acquired pneumonia at the edge of the new millenium]. PMID- 11210298 TI - [Augmentin (amoxicillin-clavulanate) and timentin (ticarcillin-clavulanate) in treatment of purulent wounds of skin and soft tissues]. PMID- 11210300 TI - [Etiology of community-acquired bronchitis and pneumonia in young children and the choice of antibacterial therapy]. PMID- 11210301 TI - [Clarithromycin and tumor chemotherapy]. PMID- 11210302 TI - [Importance of pharmacokinetic studies for antibiotic therapy in children with pneumonia]. PMID- 11210303 TI - [Secretolytic preparations and antibiotics in treatment of the acute and chronic nasal, nasal sinus, and middle ear diseases in children]. PMID- 11210304 TI - [beta-Lactams. Structure and biological activity relationship]. PMID- 11210305 TI - [Non-sporulating anaerobic bacteria and anastomosis failure in patients with gastric carcinoma]. AB - Cases of anastomosis suture failure within the period from 1977 to 1987 and from 1988 to 1998 in 139 patients after various surgical operations for gastric carcinoma were analyzed. Infection in the cases of the anastomosis sUture failure at the early terms was mainly due to representatives of Enterobacteriaceae and at the later terms the failure was mainly due to non-sporulating anaerobes belonging to Bacteroidaceae. The data are indicative of the fact that the use of antimicrobials requires a differential approach. PMID- 11210306 TI - [Comparative morphological analysis of the articular cartilage, epiphyseal plate, spongy bone, and synovial membrane of the knee joint in children treated and not treated with ciprofloxacin]. AB - Comparative data on he postmortem morphological examination of the knee joint in children treated and not treated with ciprofloxacin while alive are presented. Nine children were ill with mucoviscidosis and 8 children were ill with aplastic anemia. The patients were ill with mucoviscidosis and 8 children were ill with aplastic anemia. The patients were treated with ciprofloxacin in a daily dose of 20 to 40 mg/kg body weight at the average for 148 days. The condition of the articular cartilage, growth area, spongy bone and synovial membrane of the knee joint was examined visually, histologically and morphologically. It was revealed that ciprofloxacin had no chondrotoxic effect. The structure affected in some cases by the ciprofloxacin treatment was the synovial membrane which developed subacute synovitis not clinically manifested (latent) in life. The phenomenon is explained. PMID- 11210307 TI - [Minimally invasive coronary artery bypass surgery]. AB - From 19.06.97 to 06.01.2000 36 patients with coronary heart disease underwent direct myocardium revascularization surgery by minimally invasive method (through minithoracotomy, off-pump and on the beating heart), anastomosis between left internal mammaria artery and anterior descending artery (ADA). The majority of the patients (55.6%) had one-vessel damage of ADA coronary bed, in the patients with damage of two and more vessels full revascularization of coronary bed was achieved by two coronary arteries bypass at once or by combination of minimally invasive coronary bypass (MICB) with PTCA. MICB is performed in specially selected patients according to stuct indications. Technique of operation, early postoperative course, possibilities of combination of MICB with other methods of treatment is described. Potential of MICB is discussed. PMID- 11210308 TI - [Diagnosis and treatment heart and pericardium wounds]. AB - The experience of diagnosis and treatment of heart and pericardium wounds in 152 patients are presented. In obecure diagnosis the authors prefer X-ray examination and echocardiography. Total lethality was 23.6%. Its high level is due to injury of coronary arteries and intracardiac structures, other thoracic and abdominal organs. The left anterolaferal thoracotomy is the optimum approach in wounds of the heart and pericardium. The most frequent complication of postoperative period is pericarditis, its echographic symptoms were revealed in 91% examinys. Non steroid and steroid antiinflammatory drugs are effective for prophylaxis and treatment of pericarditis. PMID- 11210309 TI - [One-stage combined operations on kidney and other organs]. AB - Patients with combined diseases of the kidney, organs of abdominal cavity and retroperitoneal space require original decisions in the choice of surgical approach and sequence of interventions on different organs. The experience of one stage combined nephrectomies and kidney resections in 36 patients with lung, stomach, intestine, liver and other organs' diseases are presented. 11 patients had primary renal carcinoma, the kidneys were affected by other malignant tumors in 15 patients. Primary benign processes in the kidneys were found in 3 patients and also in 7 patients these processes were the consequence of earlier performed operations. Interventions on 3-6 organs were necessary in 11 cases. It makes sense to begin one-stage combined transperitoneal interventions with "clean" stages--without section of gastrointestinal tract's lumen. 1 patient died because of peritonitis due to insufficiency of sutures of colon anastomosis. The follow up ranged from 6 months to 12 years. The recurrences and metastases were found in 9 operated patients within 7 to 20 months, and there were no symptoms of diseases in 24 patients. It is concluded that extended radical one-stage operations on the organs of abdominal cavity and retroperitoneal space combined with operations on the kidney are endurable and effective if the surgical technique is thorough. PMID- 11210310 TI - [Pressing problems of gastric and duodenal ulcer surgery]. AB - Main types of surgical operations for the treatment of ulcer disease were elaborated towards the end of XIX century and improved constantly for the better by surgeons. Vagotomy is the outstanding achievement of the XX century. It enabled lowering of mortality, and frequency of postresection syndromes and improved patients' quality of life. The discovery of Helicobacter pylori (Hp) has changed our knowledge about ulcer disease pathophysiology. Eradication of Hp with omeprasol and antibiotics sharply improved the treatment, decreased the relapses. In this connection number of elective surgical operations decreased, but number of emergency increased. Importance of Hp in pathophysiology of ulcer disease is overestimated. Chronic Hp gastritis, destroying protective mucosal barrier clear the way for destructive action ofacidopeptic component of gastric juice and ulcer formation. The comparative evaluation of different surgical operations is given and optimal methods for the treatment of complicated and uncomplicated duodenal and gastric ulcers are recommended. PMID- 11210311 TI - [Diagnosis and surgical treatment of arterial hypertension of adrenal origin]. AB - 230 patients with arterial hypertension of adrenal origin were treated. 205 of them underwent adrenalectomy with surrounding paranephral fat. There were no lethal outcomes. Endogenic adrenocorticism was diagnosed in 134 patients. Cushing's syndrom was in 96 patients, Cushing's disease--in 34, ACTH-ectopic syndrome--in 2, adrenocortical cancer--in 2. Primary hyperaldosteronism was diagnosed in 42 cases: idiopathic hyperaldosteronism in 23 patients, aldosteronproducing adenoma (Conn's syndrome)--in 19. Tumors of chromaffine tissue were defected in 30 patients. All the patients underwent complex examination (hormonal profile, US, CT, MRT, angiography if it was necessary). Symptomatic arterial hypertension of adrenal origin was diagnosed during one year in 10% patients only because of absence of typical clinical picture. Use of complex examination has permitted to make a correct topical diagnosis and to choose optimum treatment policy in all the cases. PMID- 11210312 TI - [Radical surgical treatment of Barrett's esophagus]. AB - In the light of modern scientific knowledge, pathogenesis of Barrette's esophagus (BE) is presented as an integral neoplastic process. Indications to operation and policy of radical surgical treatment in BE, including in combined esophageal diseases (burn and peptic strictures, reflux esophagitis, short esophagus) were developed. From 1990 to 2000 radical operations were performed in 14 patients (11 males, 3 females) with BE. Mean age was 54.1 years. About 80% patients had clinical signs of reflux esophagitis at the moment of hospitalization. In all the patients the diagnosis of BE was verified in microscopic examination of operative material. 4 patients with cylindrical metaplasia associated with ulcers and esophageal peptic strictures were operated, 3 patients--with epithelium dysplasia, 7 patients--with adenocarcinoma. All the patients underwent extirpation of thoracic portion of esophagus with one-stage plasty with isoperistaltic gastric tube, supplemented with mediastinal and abdominal lymphodissection in cancer. Affection of the regional lymph nodes was revealed in 43% patients with esophageal adenocarcinoma. 50% patients had complications in postoperative period. There were no cases of hospital lethality. The expansion of indications for early surgical treatment of BE at the stage of meta-, and dysplasia, before adenocarcinoma development, is thought valid. PMID- 11210313 TI - [Assessment of pancreatoduodenal resection completion methods]. AB - The nearest outcomes of 305 pancreatoduodenal resections (PDR) for malignant and benign diseases of the pancreas head and periampullar zone are presented. Necessity of differential approach to choice of method of pancreatodigestive anastomosis formation is demonstrated. In unectatic main duct of the pancreas and unchanged pancreatic parenchyma there is a high risk of postoperative pancreatitis and lethal outcome which achieved 29.8% in the group of 57 patients. In patients with diameter of main pancreatic duct more than 3 mm and fibrotic changes of its parenchyma, the majority of methods of pancreas inclusion the in digestive canal were characterized by favorable results, lethality was 7.7% among 248 patients. Recently, the increase of rate of PDR with pylorus preservation permits to apply widely pancreato-, bilio-, and duodenoenteroanastomosis on the same jejunal loop. PMID- 11210314 TI - [Treatment of extrahepatic bile ducts injuries due to laparoscopic cholecystectomy]. AB - The department of hepatic surgery of I.M. Sechenov Moscow Medical Academy has gained experience of treatment of 25 patients with injuries of bile ducts inficted in laparoscopic cholecystectomy (LCE). All the patients underwent LCE in other hospitals. 4 patients were hospitalized with recent injuries (within 24 hours after injury) and 21--later. Injuries of the duct in LCE characterized by early clinical manifestation, injury in proximal portion of hepatic duct, technical difficulties of anastomosis creation during the first operation due to thin-walled duct of small diameter. Reconstructive operations yielded good results in 22 patients. Recurrent strictures were revealed in 3 patients who required repeated intervention. There were no lethal outcomes. PMID- 11210316 TI - [Ultrasonic diagnosis of focal damages in thoracoscopic operations]. AB - 5-year experience of developed in PAMS A.V. Vishnevsky Institute of Surgery RAMS ultrasonic examination (USE) of the lung in thoracoscopic operations for focal lung lesions (FLL) is presented. Pilot experience of ultrasonic topical and differential diagnosis of FII opens a new page in diagnosis of respiratory diseases. Over 5 years 74 USE of FLL were performed. FLL were found in 91% cases. Detailed topical diagnosis of allows to design the lung resection with the best functional result. In postoperative X-ray examination neither atelectases nor zones of stable hypoventilation were detected. Normal echographic picture of lung tissue and echosemiotics of different focal lesions are descubed. The experience of diagnosis by echographic signs of FLL shows teasibility of differentiation of hamartomas from tuberculomas and focal metastatic lesions. The payential of differential diagnosis is illustrated. Differential diagnosis supported enucleation in superficial hamartomas and resection in suspected malignant tumor or tuberculosis. Use of intraoperative USE in the majority of cases of focal lesions located both in depth of lung tissue and subpleurally warrants the success of operation in thoracoscopic variant. PMID- 11210315 TI - [Thoracoabscessotomy in combined treatment of lung gangrene]. AB - Patients with gangrene and gangrenous abscess of the lung belong to the most severe group of patients with purulent lung diseases. Conservative treatment is not effective, lethality after lung resection or pneumonectomy ranges from 20 to 70%, therefore the study of less traumatic but life-saving operations is topical. From 1996 to 1998, 296 patients with purulent destructive processes in the lung were hospitalized, 34 of them had gangrene or gangrenous abscess of the lung with significant intoxication. Thoracoabscessostomy by original method with consecutive necrectomies, sanitation of purulent cavity was performed in 27 patients. After operation 2 patients died, 25 patients were discharged with clinical recovery in satisfactory conditions, with dry cavity in the lung. In remote terms the cavities are cicatrized or transform to spurious cysts. Indications for thoracoabscessostomy are formulated. It is method of choice in the treatment of patients with gangrenous lung abscess, when conservative treatment is not effective, but the risk of radical operation is very high. PMID- 11210317 TI - [Is reliable prophylaxis of postoperative venous thromboembolic complications possible?]. AB - Thrombosis of deep veins of lower extremities and pelvis is found in every third operated patient on the average, pulmonary embolism--in 0.5-0.8% cases. The results of nonspecific and specific prophylaxis of these complications are reviewed in the article. Intermittent pneumatic compression, compressive elastic stockings and standard or low-molecular heparin administration are most effective. Prophylactic measures do not exclude completely possibility of venous thromboembolic complications, but permit to control reliably this danger. The author has an experience of cavafilter implantation in 147 patients. PMID- 11210318 TI - [Prophylaxis of laryngeal nerve injuries in thyroid surgery]. AB - The problem of injury of recurrent laryngeal nerve (RLN) is topical despite large usage and detailed development of surgical treatment of thyroid gland (TG). The results of 3603 operations on TG were analyzed. The 1st group consisted of 560 patients operated in 1981-1988 by O.V. Nikolaev's method without dissection of RLN, the 2nd group--3043 patients operated in 1989-1998 with intraoperative imaging of RLN on the one or two sides. In the 1st group the injury of RLN was revealed in 39 (7.0%) patients, in 4 of them--bilateral. In 2nd group it was revealed in 10 (0.3%) patients. Present data lead to a conclusion that intraoperative imaging of RLN in operation on the thyroid gland is necessary. PMID- 11210319 TI - [Ultrasonic examinations of thyroid newgrowths]. AB - The results of complex ultrasonic, histological and cytological examination of 148 patients with newgrowths thyroid were analyzed. Grey-scale mode, colored and energy Doppler scanning, three-dimensional reconstruction of vessels were used. A new classification of nodular vascular pattern types based on 3-D reconstruction is proposed. The majority of malignant formations were characterized by perinodular hypervascularization and internodular hypovascularization (82.4%), adenomas--by peri- and intranodular hypervascularization (88.9%), colloid nodes- by perinodular hypervascularization (85.5%), the blood flow was absent in simple cysts (85.3%). It was established that complex of these methods increases informative value of ultrasonic examination in diagnosis of thyroid nodular diseases: in malignant neoplasms the sensitivity is 92.9%, specificity--86.1%, diagnostic accuracy--86.9%, in adenomas--93.4%, 79.2% and 82%, in colloid nodes- 75.7%, 84.1% and 79.8%, respectively. In cystic masses diagnostic value of Doppler methods didn't change: sensitivity was 90.4%, specificity--63%, diagnostic accuracy--80.5%. The combined ultrasonic examination provides a differential approach to treatment of patients with thyroid nodular masses and decreases the number of unjustified surgical interventions. PMID- 11210320 TI - [Extracorporeal detoxication in combined treatment of surgical sepsis]. AB - The methods of extracorporeal detoxication acquire special importance in combined treatment of sepsis. The sessions of plasmapheresis, hemodialysis and isolated ultrafiltration were performed in 61 of 83 patients with sepsis. Indications to these methods are determined, their efficacy is evaluated. It is established that administration of antibiotics and immunoglobulins after sessions of plasmapheresis and hemodialysis to achieves therapeutic drug concentration in blood. It is difficult to select the dose of antibiotics and immunodrugs in permanent round-the-clock ultrafiltration since the part of them are eliminated through the filters. Overall lethality was 20.4% (17 of 83 patients died), in the group of patients with severe polyorganic insufficiency and septic shock who needed extracorporeal detoxication--27%. PMID- 11210321 TI - [Ambulatory surgical interventions in patients with proctological diseases]. AB - The results of 629 operations for the most frequent proctological diseases (hemorrhoid, anal scissure, rectal fistula, acute paraproctitis) were analyzed. 134 operations were performed in outpatient clinic, 225--in one-day hospital and 270 (control group)--in coloproctology department. The place of operation did not influence postoperative period and temporary disability time. The mean stay of patient in outpatient department and hospital surgical unit was 3.8 and 324 hours, respectively. Since the second day after operation in specialized department it is possible to perform therapeutic manipulations outpatient in coloproctology room without negative sequences for patient's health. Cost of the ambulatory operation constituted 28.4% of hospital stay for patients with similar interventions. Surgical treatment of the above diseases could be performed in outpatients setfing in more than 50% patients. The bed resources must be used for patients who need long-term and intensive treatment in specialized department. PMID- 11210322 TI - [Determination of colon resection limits in diverticulosis]. AB - Results of surgical treatment of 112 patients with colon diverticulosis are analyzed. It is established that during operation it is necessary to perform such scope of resection which permits to create anastomosis between colon parts without their discoordination. The risk of complications from anastomosis decreases to 3.7%. The creation of anastomosis with significant discoordination leads to high risk of its insufficiency. It is desirable to resect the colon's parts with moderate discoordination. When the extension of of resection margins due to parts with moderate discoordination is dangerous, it is possible to create the anastomosis with ileo- or colostoma. In this case the risk of inflammatory complications remains, but conservative treatment of these complications in the conditions of feces efflux is effective. PMID- 11210323 TI - [Use of topical medicines to reach a definite hemostasis during hepatic resection]. PMID- 11210324 TI - Occupational disease in Connecticut, 2000. AB - This study was designed to establish the magnitude and distribution of reported occupational diseases in Connecticut based on 1998 data. Occupational disease is a reportable disease in Connecticut, yet is under-reported particularly for chronic conditions. The number of reported occupational diseases was 3,556 from workers' compensation reports, 1,444 from physician reports, and 5,510 from the Connecticut OSHA-Labor Department survey. Musculoskeletal disorders dominate the reports in all three databases, ranging from 46% to 62% of all illness reports. Skin conditions range from 8% to 18%; lung conditions from 9% to 16%; and infections from 1% to 18%. There are approximately 1.52 million workers in Connecticut, which results in a rate of 36.2 cases of occupational disease per 10,000 workers based on the Bureau of Labor Statistics figures. These conditions are broken down by type, industry, and cause. Improved identification of work linkages can lead to better treatment and job placement, as well as improved prevention. PMID- 11210325 TI - Cytochrome P-450 drug interactions and the selective serotonin reuptake inhibiting antidepressants. PMID- 11210326 TI - The future of managed care in Connecticut. PMID- 11210327 TI - Azithromycin. PMID- 11210328 TI - The human side. PMID- 11210330 TI - Address of the Executive Director. CSMS House of Delegates--semi-annual meeting 8 November 2000. PMID- 11210331 TI - Prevalence, capsular type distribution, anthropometric and obstetric factors of group B Streptococcus (Streptococcus agalactiae) colonization in pregnancy. AB - OBJECTIVE: To establish the prevalence, serotype distribution, anthropometry and obstetric factors of Group B Streptococcus (GBS) colonization in pregnant women. DESIGN: Cross sectional survey. SETTING: Chinhoyi General Hospital. SUBJECTS: 206 pregnant women attending the antenatal clinic at Chinhoyi General Hospital were systematically randomly sampled. MAIN OUTCOME MEASURES: All the isolates were serotyped on the basis of capsular polysaccharide (CHO) antigen designated, Ia, Ib, II, III, IV and V. RESULTS: 65 (31.6%) were carriers of GBS. The serotypes found were, type III (41.8%), type V (37.4%), type Ia (11.0%), type IV (3.3%), type Ib (3.3%) type II (1.0%) and 2.0% of the isolates were non-typable. All isolates were sensitive to penicillin and resistant to gentamycin. Colonization was more common in women with parity 0 to 2 (4.6%) and age group 20 to 24 years (43.1%). There was some evidence (p = 0.063) to suggest that GBS was more often isolated from the vagina (12.6%) than from the rectum (6.3%). CONCLUSION: There was a high prevalence of GBS colonization among pregnant women in Chinhoyi. Types III and V were the most common serotypes found. PMID- 11210332 TI - Haematology reference values for healthy elderly blacks residing in Harare, Zimbabwe. AB - OBJECTIVES: To determine reference values for elderly blacks and to compare them to those in use in local hospitals and in other countries in the region. DESIGN: Cross sectional study. SETTING: Sekuru Kaguvi Hospital, Harare, Zimbabwe. SUBJECTS: 151 persons of age 45 years or more. MAIN OUTCOMES MEASURES: Haematological parameters investigated were Hb, Hct, MCV, MCH, MCHC, Plt, RBC and WBC. RESULTS: 56 males and 95 females tok part in the study. RBC, Hb and Hct mean values were significantly higher (p=0.004, p<0.001 and p<0.001, respectively) in males than in females. However, no significant differences between sexes were found in WBC (p=0.137), MCHC (p=0.273), MCV (p=0.090) and MCH (p=0.074). Platelet counts were significantly higher (p=0.040) in females [median (Q1, Q3): 251 (117, 478)] than in males, 226 (122, 251). These haematogological vales were notably different compared with those in current use in local hospitals. The mean values obtained for each index were comparable with those obtanied in other countries in the same region (Southern Africa) as Harare. The reference values for the elderly blacks are presented. CONCLUSION: The importance of gender and population specific reference values cannot be over emphasised. The reference values obtained in the current study should be appropriate for evaluating haematological test results in elderly blacks in Zimbabwe. PMID- 11210333 TI - Comparison of wheelchair accessibility of public buildings pre and post the International Year of Disabled Persons (IYDP) in Harare, Zimbabwe: a case study. AB - OBJECTIVE: To compare the accessibility to wheelchair users of public buildings built pre and post the International Year of the Disabled Persons (1981) in Harare central business district in Zimbabwe. DESIGN: A case study. SETTING: Harare central business district. SUBJECTS: 20 public buildings with at least two floors open to all users in the central business district of Harare, Zimbabwe. MAIN OUTCOME MEASURES: Wheelchair accessibility of public buildings. RESULTS: There were no significant differences in the median percentage compliance of parking areas (p = 0.546), ramps (p = 0.155) and toilets (p = 0.648) between the buildings built before the International Year of the Disabled Persons (IYDP) and those built after the IYDP. The overall median compliance of parking areas, ramps and toilets was 14% (Q1 = 14, Q3 = 21), 54% (Q1 = 43, Q3 = 62) and 45% (Q1 = 31.5, Q3 = 70), respectively. However, there was some evidence (p = 0.067) to suggest that compliance of entrances was better IYDP [median = 100% (Q1 = 90, Q3 = 100)] than pre IYDP [median = 80% (Q1 = 70, Q3 = 100)]. Meanwhile there was a significant difference in the median percentage compliance of elevators (p = 0.014) between pre[median = 90% (Q1 = 80, Q3 = 90)] and post [median = 100% (Q1 = 100, Q3 = 100)] IYDP. CONCLUSION: Overall compliance was poor. It is recommended that people with disabilities and the experts in the area of physical ability management be consulted and involved in the design and construction of these buildings. PMID- 11210334 TI - Tru-cut biopsy of palpable breast lesions: a practical option for pre-operative diagnosis in developing countries. AB - OBJECTIVES: To establish the role of Tru-cut needle biopsy in the pre-operative diagnosis of breast lesions in a developing country. DESIGN: Prospective cross sectional study. SUBJECTS: 112 consecutive patients with palpable breast lesions who had both Tru-cut and excision biopsy as a pre-operative diagnostic procedure. RESULTS: Four (3.6%) patients had specimens that were inadequate for histological diagnosis. Tru-cut biopsy diagnosed 42 of the remaining 108 as malignant and 66 as benign, but only 40 and 61 respectively were confirmed to be correctly so by excision biopsy. Tru-cut biopsy, therefore, achieved a sensitivity of 88.9% (95% CI 79.7 to 98.1) specificity of 96.8% (95% CI 92.5 to 100) and an over all diagnostic accuracy of 93.5% (95% CI 88.9 to 98.2). There was a false positive rate of 4.8%, a false negative rate of 7.6% and a positive predictive value of 95.2%. The pathologist was able to make a correct specific histological diagnosis in 76.2% of all the adequate Tru-cut samples. CONCLUSION: If Tru-cut biopsy is done instead of excision biopsy, it will sufficiently reduce waiting time and reduce cost (four fold). It is well tolerated by patients. We regard the procedure as a useful adjunct and indeed a practical option for accurate pre operative diagnosis of palpable breast lesions. PMID- 11210335 TI - Rectus abdominis myocutaneous flap in reconstruction for advanced male breast cancer: case report. AB - A case of advanced male breast cancer which masqueraded as recurrent abscess of the right breast is presented to highlight the role of contra-lateral rectus abdominis pedicled myocutaneous flap in providing adequate skin and soft tissue cover in male breast reconstruction. This was carried out for this patient following a modified radical mastectomy for stage III (T2b, N2, M0) intraductal carcinoma of the breast. The patient has remained well without clinical features of distant metastasis at a follow up period of two years despite periodic excision of locally recurrent cancer nodules from the affected breast. PMID- 11210336 TI - Current concepts in the management of acute ischaemic stroke. PMID- 11210337 TI - Diagnosis of neurological infections in AIDS patients: possibilities for Zimbabwe. PMID- 11210338 TI - Preliminary study of body mass index and its relationship to percent body fat in Harare, Zimbabwe. AB - OBJECTIVES: The aims of this paper were to document the body mass index (BMI) and anthropometric characteristics of the city of Harare urban dwellers of Zimbabwe. To investigate the relationship between BMI, sum of skin folds (SSF) and percent body fat (PBF). DESIGN: Cross sectional study. SETTING: Designated fitness awareness locations in the city of Harare during the 1998 physiotherapy awareness week. SUBJECTS: The participants were 140 apparently healthy adults, males (n = 71) and females (n = 69). MAIN OUTCOME MEASURE: Body Mass Index. RESULT: The minimum and maximum values of BMI were 17.7 and 33.3 for men, 17.6 and 47.8 for women. BMI was not found to increase with aging but PBF on the contrary did. The mean BMI value for the males and females was 24.89 +/- 3.18 and 27.8 +/- 5.89 respectively. There was no significant difference in mean BMI between sexes (p = 0.331). Weight was also similar by gender (p = 0.4691). In both sexes, the BMI showed a significant positive correlation with PBF, SSF, body weight and age (for males r = 0.721, 0.731, 0.900, 0.369, p < 0.01 respectively; and in females r = 0.786, 0.804, 0.940, 0.404 and p < 0.01 respectively). CONCLUSION: Women were found to have higher BMI, PBF, SSF than their male counterparts. On the average, men were found to be taller, with no significant difference in weight. There was a linear relationship between BMI and PBF, and all the variables investigated except age and stature in both sexes. Because of the differences of environment and industrialisation, estimation of BMI should involve such factors as ethnicity, race, gender and age. PMID- 11210339 TI - Ethics and HIV research in Zimbabwe. AB - A plethora of articles are now being published in both local and international journals on research activities conducted on the human immunodeficiency virus (HIV) in Zimbabwe. Some of the bioethical issues they raise, however, are neither unique to HIV nor unique to developing countries. In this article we discuss several of these issues, including the failure to provide interventions of known efficacy, ethical relevance of study design, informed consent, and exploitation. A challenge raised by much of the research in HIV/AIDS is whether, or under what conditions, it is ethical in research to fail to provide an intervention of known efficacy. The further we diverge from this situation, in which an effective, easy to implement intervention is available, to situations that resemble the controversial international clinical trials to prevent perinatal transmission of HIV the less clear the ethical mandate becomes. In relation to clinical trials the debate has focused on whether the standard of care in the United States--an expensive and complex regimen of Zidovudine--must be provided to all HIV infected pregnant women who join a research study in developing countries. Different scientists and scholars in bioethics have drawn the line differently in terms of what interventions routinely available in the developed world must be provided to research participants in developing countries. At an extreme, no one suggests that the most expensive and complex of Western tertiary care, for example, renal dialysis or coronary bypass, must be provided in research conducted in Zimbabwe. Indeed, public debates about the HIV perinatal transmission trials have not even focused on whether the women in the trials should be provided with HIV combination therapy as they would be in the West or whether they should even have the Zidovudine continued post partum. PMID- 11210340 TI - Ethical issues in clinical and industry-sponsored research. PMID- 11210341 TI - Antiretrovial (ARV) drug utilisation in Harare. AB - OBJECTIVE: To investigate ARV utilisation in Harare in order to gather necessary data to help in the formulation of treatment guidelines to be used in Zimbabwe. DESIGN: A cross sectional study. SETTING: Doctors' rooms and retail pharmacy outlets. SUBJECTS: 68 primary care physicians, 80 pharmacists and 92 patients. MAIN OUTCOME MEASURES: Number of physicians prescribing antiretroviral agents (ARVs) and pharmacists stocking ARVs. Type of ARV utilised, cost to the patient and information on ARV available. RESULTS: Out of the 68 private practitioners interviewed 18 were prescribing ARVs during the period of study. There were 92 patients on ARVs whose mean age was 35 +/- 5 years and consuming an average total of 17 tablets daily. Thirteen out of the 18 doctors had access to laboratory facilities to determine CD4 counts and viral load. The rest were using other approaches to treat and manage HIV/AIDS patients. About a quarter, 27.0%, of the retail pharmacists stocked ARVs. The majority, 82.0%, of the patients appeared to be on Zidovudine (AZT) mainly in combination with other drugs. The most popular combination was that of AZT, Lamivudine (3TC) and Indinavir prescribed to 29.0% of the patients, followed by that of Didanosine (DDI) and hydroxyurea prescribed to 17% of patients. At least 17% of the patients were on AZT monotherapy. There was no significant difference (p = 0.06) in the number of tablets consumed by patients who had other conditions secondary to HIV infection. Only 39 out of the 92 patients reported untoward experiences with ARVs. The major problem being associated gastro-intestinal disturbance which accounted for 56% of the reports. It was not possible to ascertain adherence. CONCLUSION: There appeared to be therapeutic anarchy in the private sector in Harare in the way ARVs were being used. Patients need to be told that deciding to take one of the combinations means making a serious commitment to the drugs on schedule if they want to enjoy the benefit. At the same time there is need to develop and publicize HIV/AIDS treatment guidelines and effective Information, Education and Communication (IEC) materials specific to Zimbabwe. PMID- 11210342 TI - Anorectal trauma in children. AB - OBJECTIVES: To determine the pattern and magnitude of the problem of anorectal injuries at the University of Calabar Teaching Hospital. DESIGN: Prospective cross sectional descriptive study. SETTING: Department of Surgery, College of Medical Sciences, University of Calabar, Nigeria. SUBJECTS: 51 consecutive paediatric patients treated for anorectal injuries over a three year period. MAIN OUTCOME MEASURES: Mechanism of rectal injury, contributing factors, anatomic region injured, length of hospital stay, complications and outcome. PMID- 11210343 TI - Perinatal practices in two rural districts of Zimbabwe: a community perspective. AB - OBJECTIVE: To describe perinatal practices from a community perspective and identify factors associated with perinatal death. DESIGN: Cross sectional community based survey. SETTING: Murewa and Madziwa rural areas, Zimbabwe. SUBJECTS: Women aged 15 to 50 years who had been pregnant within the 24 months preceding the survey. MAIN OUTCOME MEASURES: Where delivered, where preferred to deliver, model of delivery, use of herbs in labour, duration of labour, assistant at delivery, time of delivery, condition of baby at birth, resuscitation methods, birth weight, initiation of breast feeding, illness in the first week and outcome of pregnancy. RESULTS: 644 women were interviewed; 581/644 stated where they would have liked to deliver and 505/644 stated where they actually delivered their last baby. The majority 369/581 (62.4%) preferred to delivery at a government hospital and 240/505 (47.5%) actually delivered at a government hospital. Of the home deliveries only 27/581 (4.6%) preferred to deliver at home and yet 123/505 (24.4%) actually delivered at home. Primary care clinics were less preferred 151/581 (25.5%) as a place for delivery and 89/505 (17.6%) actually delivered there. Labour lasting more than 12 hours occurred in 20.4% of deliveries. Nurses were the commonest attendants at delivery 309/508 (60.4%) and morbidity following delivery was noted in 72/495 (14.5%). Resuscitation was carried out in 61/72 infants. Beating/shaking 36/61 (58.0%) and pouring cold water over the baby 11/61 (18.0%) were the commonest methods of resuscitation. Being delivered by a doctor compared to a nurse and being in Murewa district were statistically significant risk factors for mortality with Odds Ratio (OR) 5.21 (95% CI 2.86 to 9.51) and 3.90 (95% CI 1.51 to 10.09) respectively. The odds of dying when delivered by breech extraction were high, but not statistically significant OR 3.73 (95% CI 0.92 to 13.97) when compared to being delivered by vertex delivery. Labour more than 12 hours, use of herbs in pregnancy and time of delivery were not significantly associated with mortality with OR (95% CI) of 1.02 (0.40 to 2.19), 0.92 (0.00 to 4.38), 1.05 (0.56 to 1.97) respectively. On logistic regression analysis only being delivered in Murewa district remained significant. CONCLUSION: The utilisation of primary health care centres for delivery was unexpectedly low and home deliveries were unacceptably high. Increased mortality when delivered by a doctor and high early neonatal morbidity suggest poor monitoring and delayed intervention in labour. Infant morbidity following delivery was high and methods for neonatal resuscitation inappropriate. There is a need for more studies looking into health worker skills particularly in the areas of partogram use and neonatal resuscitation in these districts. PMID- 11210344 TI - [Cryoglobulins and cryoglobulinemia]. PMID- 11210345 TI - [Coronary insufficiency and metabolic hormone ratio in patients with myocardial infarction in the course of a long prospective study]. AB - An angiographic study of coronary bed status and relationships of insulin, cortisol, somatotropin (ST), T3, T4, glucose in 109 Q-wave myocardial infarction (MI) patients aged 47 +/- 0.8 years was performed at rest and during veloergometric stress-test ischemia modelling of exercise tolerance in early (21 26 days) and late (> 5 years) follow-up. The hormones level was found to be significantly related to coronary insufficiency as a result of coronary atherosclerosis both at rest and during muscular stress-test. Coronary failure limiting activity of metabolic processes in the myocardium by chronic hypoxia induces changed proportion of hormones regulating energy metabolism processes. In MI hypometabolic syndrome is developing with specific hormonal "ischemic profile" in which during exercise insulin and thyroxin become leading hormones regulating intracellular exchange of energy; the level of cortisol and ST decreases. Increased need in glucose as a main energy substrate during ischemia and therefore in insulin leads to disturbed carbohydrate metabolism in 33% of patients recorded 3-5 years after MI. The above metabolic changes manifest with increased glucose tolerance and/or clinical signs of diabetes mellitus. PMID- 11210346 TI - [Efficiency of endobronchial laser therapy in patients with chronic bronchitis]. AB - Clinical effectiveness of endobronchial laser therapy (EBLT) was studied in 18-56 year-old patients with chronic bronchitis (CB) running for 2-18 years. A parallel luminescent and histochemical tests measured histamine, serotonin and catecholamines in bronchial mucosa. It was found that alveolar macrophages, lymphocytes and mucus of CB patients contain significantly higher amounts of histamine and serotonin though low amounts of catecholamines than those of healthy subjects. Levels of monoamines in alveolar macrophages, lymphocytes, neutrophils, mast and APUD cells, mucus in of CB patients correlated with the disease phase, duration, features of endobronchitis, bronchial obstruction and severity of respiratory insufficiency. EBLT produced a positive effect on CB course and bronchial mucosa bioamines. It was superior to conventional therapy in lowering of histamine and serotonin in alveolar macrophages, lymphocytes and mucus as well as in raising catecholamines. PMID- 11210347 TI - [Fibrinolytic therapy of patients with pulmonary artery thromboembolism by tissue plasminogen activator and streptokinase preparations]. AB - Changes in clinical and hemodynamic indices, hemostatic system during therapy with plasminogen tissue activator and streptokinase drugs were studied in 49 patients with massive and submassive forms of pulmonary thromboembolism. Conduction of fibrinolytic therapy with plasminogen tissue activator vs streptokinase produced more marked and rapid change in the main hemodynamic parameters which characterized blood recovery in pulmonary artery. A correlation was revealed between the change in hemostatic system after thrombolytic therapy and development of hemorrhagic complications. Preferable introduction of plasminogen tissue activator is shown when thromboemboli locate in the trunk or in both main pulmonary arteries and in the presence of an occlusive lesion in lobular arteries. PMID- 11210348 TI - [Six-minute walking test for the evaluation of the status of patients with chronic cardiac failure]. AB - The paper presents the results of application of the modified 6-minute walking test for assessment of exercise tolerance in follow-up of patients with ischemic heart disease (IHD) complicated by chronic cardiac failure (CCF). At admission and after 3-4 weeks of treatment 52 IHD patients underwent the walking test and described subjective effects according to modified Borg's questionnaire. The repeated test registered increased walking distance and subjective response. The results of the study confirm validity of using 6-minute walk test in combination with modified Borg questionnaire in routine hospital and outpatient practice as a simple, safe and informative method of control over IHD patients' condition and assessment of their treatment efficacy. PMID- 11210349 TI - [Psychovegetative changes and their correction in patients with peptide ulcer]. AB - The study of the psychovegetative status in 106 duodenal ulcer patients discovered alterations in this status. Different treatments were employed, among them--acupuncture with low-frequency alternating magnetic field. The latter had a positive effect on emotional and personality spheres, vegetative regulation, shortened the relief of the basic symptoms, scarring of the ulcer defect. PMID- 11210350 TI - [Effects of halotherapy on free radical oxidation in patients with chronic bronchitis]. AB - Registration of luminol-dependent chemoluminescence of blood cells and iron induced chemoluminescence of the serum was used to study generation of active oxygen forms and lipid peroxidation in patients with chronic bronchitis (CB). 49 patients with lingering CB showed inhibition of blood cell function and enhancement of lipid peroxidation. The addition of halotherapy to combined treatment of these patients promoted correction of the disorders and improvement of CB course. PMID- 11210351 TI - [Genetic aspects of essential arterial hypertension (summing up the 8th and 9th European Conferences on Arterial Hypertension]. PMID- 11210352 TI - [Renal involvement in convalescents after icterohemorrhagic leptospirosis]. AB - Icterohemorrhagic spirochetosis convalescents develop slowly regressing renal dysfunctions most frequent of which are chronic renal failure, pyelonephritis and tubulointersticial nephritis, arterial hypertension. Renal disorders may be due to immunopathological reactions followed by activation of bacterial microflora. Damage from commissures at the sites of prior hemorrhage is also possible. In bovine leptospirosis renal damage is not so severe but it tends to progression. So, renal affection in leptospirosis is a specific pathology observed in any clinical form of the disease and demands surveillance in the regions of local focuses. PMID- 11210353 TI - [Therapy of patients with chronic pancreatitis of alcoholic etiology by dalagrin and laser therapy of the blood]. AB - Effectiveness of dalargin and intravenous laser blood beaming (ILBB) in combined treatment of chronic alcoholic pancreatitis (CAP) was studied in 105 patients (8 females and 97 males) with CAP duration 1 to 25 years. Pancreatic function and treatment effects were studied by routine clinical investigations, advanced laboratory, biochemical tests, radioimmunossays. Pancreatic disorders in alcoholics present with high blood levels of trypsin and lipase, low levels of insulin and C-peptide. Serum concentrations of hydrocortisone and gastrin were elevated. Combined treatment of CAP with adjuvant dalargin and ILBB not only relieves clinical symptoms but also promotes normalization of pancreatic function. PMID- 11210354 TI - [Effect of dilren on hemodynamics of patients with essential hypertension]. AB - Changes in hemodynamics and circadian rhythms in the course of dilren-300 treatment were studied in 20 patients with hypertension stage II. Tetrapolar chest rheography, echo-CG, ECG, measurements of arterial pressure by N. S. Korotkov were made 6 times a days (at 2, 6, 10 a.m. and 2, 6, 10 p.m.). The information was processed statistically. Dilren -300, administered at 8.00 a.m. for 10 days, had a hypotensive, vasodilating and weak negative chronotropic effect. The drug reduced myocardial energy consumption, eliminated circadian rhythms of heart rate, arterial pressure, cardiac performance and others observed before the treatment. PMID- 11210355 TI - [Laxigal effectiveness in constipation of various etiology]. AB - The efficiency of laxigal (sodium picosulfate) was evaluated in 66 patients aged 38-73 years with the irritated bowel syndrome (IBS), inert colon, and dolichocolon. Twenty-eight patients had defecations twice a week, 26 once a week or less. Twelve patients had no spontaneous defecations. Laxigal was administered in a dose of 10-24 droplets before sleeping. Good effect was attained in 42 (64%) patients and satisfactory in 24 (36%). Good effect is more often observed in patients with IBS and dolichocolon, while in patients with inert colon the results were usually no better than satisfactory. After long (3 weeks and longer) therapy with laxigal its dose could be reduced by 30-50% without loss of effect. Laxigal induces no diarrhea, abdominal pain, decrease in electrolyte composition or other serum shifts, does not disorder hepatorenal functions. PMID- 11210356 TI - [Difficulties in the diagnosis and modern approaches to therapy of the thromboembolism of small branches of the pulmonary artery]. PMID- 11210357 TI - [Diagnostic and therapeutic policy in nodular goiter]. PMID- 11210358 TI - [A case of total variable immunodeficiency]. PMID- 11210359 TI - [Difficulties in differential diagnosis of pericardial effusion]. PMID- 11210360 TI - [Development of the idea of staged clinical education (1842-1845). Communication 1. The decision to establish departmental and hospital ambulatory clinics at the Medical Department of Moscow University]. PMID- 11210361 TI - [Memorable dates from the history of medicine in 2000]. PMID- 11210362 TI - [Pathophysiology of cardiovascular disorders in obstructive respiratory distress during sleep]. PMID- 11210363 TI - [Principles for constructing an image of the world. The Hippocratic manuscript De aeribus and the search for the middle of the world]. PMID- 11210364 TI - ["Hebraeorum Hippokrates rei medicae peritissimus fuit." On the reception of pseudo-Solomon metaphors on old age (Koh. 12.1-6) in early modern medicine]. PMID- 11210365 TI - ["Quod naturae ipsae sint morborum medicatrices." Hippocratism of Georg Ernst Stahl]. PMID- 11210367 TI - [Ethical guidelines, patient rights and physician behavior in clinical drug trials (1892-1931)]. PMID- 11210366 TI - [Ernst Haeckel and Rudolf Virchow: the dispute over the character of science in the controversy over Darwinism]. PMID- 11210368 TI - ["Slippery slope", evaluation and self-evaluation: on the history of the euthanasia debate in the periodical Ethics]. PMID- 11210369 TI - [The "medico-historical cabinet". A forgotten collection in the Nurnberg Germanic National Museum]. PMID- 11210370 TI - Assumptions concerning orthogonality in threshold-scaled versus cone-contrast colour spaces. PMID- 11210371 TI - Risking ethical insolvency: a survey of trends in criminal DNA databanking. PMID- 11210372 TI - Expert testimony by persons trained in ethical reasoning: the case of Andrew Sawatzky. PMID- 11210373 TI - Commentary: the wizard of oughts. PMID- 11210374 TI - Commentary: weighing and comparing expert testimony by medical ethicists. PMID- 11210375 TI - Rebuttal: expert ethics testimony. PMID- 11210376 TI - Response: Narcissus meets Pandora. PMID- 11210377 TI - Genetic privacy laws and patients' fear of discrimination by health insurers: the view from genetic counselors. PMID- 11210378 TI - A survey of physician training programs in risk management and communication skills for malpractice prevention. PMID- 11210379 TI - Language and reality at the end of life. PMID- 11210380 TI - Is there a lingua franca for bioethics at the end of life? PMID- 11210381 TI - A concise rebuttal. PMID- 11210382 TI - Lessons to be learned from Harvard Pilgrim HMO's fiscal roller coaster ride. PMID- 11210383 TI - Administrative developments: new human subject research guidelines for IRBs. PMID- 11210384 TI - Employment: NLRB empowers residents to unionize. PMID- 11210385 TI - ERISA: U.S. Supreme Court holds treatment decisions made by HMO physician employees do not breach fiduciary duty. PMID- 11210386 TI - ERISA: health benefit plans discriminating against providers. PMID- 11210387 TI - Ethics: English high court orders separation of conjoined twins. PMID- 11210388 TI - Discovery issues: confidentiality of medical board records. PMID- 11210389 TI - Evidence: Supreme Court of Georgia denies law firm access to hospital records. PMID- 11210390 TI - Policy: Kaiser Commission report on personal perspectives. PMID- 11210391 TI - Medicare: coverage approved for participation in clinical trials. PMID- 11210392 TI - A look at the safety profile of over-the-counter naproxen sodium: a meta analysis. AB - As the trend for Americans to self-medicate continues to increase, it becomes important to review the safety of over-the-counter (OTC) medications. This article will review the safety of an OTC analgesic, Aleve (naproxen sodium). The objective of this meta-analysis is to evaluate the frequency of occurrence of all adverse events in subjects taking various doses of OTC naproxen sodium as compared to placebo. These varying doses and dosage regimens were studied individually and consisted of 220 to 880 mg administered in single, multiple, and PRN (as needed) doses of naproxen sodium. This meta-analysis confirmed the favorable safety profile of naproxen sodium at OTC doses and established that the overall occurrence of adverse events with naproxen sodium was comparable and in some cases significantly lower than placebo. These results indicate that treatment with naproxen sodium may be highly beneficial from a clinical and economical perspective and safe when adhering to labeled directions. PMID- 11210393 TI - Pharmacokinetic/pharmacodynamic evaluation of the NHE inhibitor eniporide. AB - The aim of this study was to investigate the pharmacokinetics and pharmacodynamics of the new cardioprotective sodium/proton exchange (NHE-1) inhibitor eniporide in humans. Eniporide was administered intravenously to healthy volunteers in doses between 2.5 and 100 mg. Concentrations of parent drug and its metabolite were measured by HPLC, and the data were analyzed by noncompartmental and compartmental pharmacokinetic methods. Platelet-swelling time was determined in each subject as a biomarker to assess pharmacodynamic activity. Eniporide showed linear pharmacokinetics with an average half-life of approximately 2 hours. The mean total body clearance was 34.4 L/h. The mean volume of distribution (Vdss) was 77.5 L, and the mean residence time was 2.3 hours. An average of 43% of the dose was recovered unchanged from urine. A pharmacokinetic two-compartment model was found suitable to provide excellent curve fits of the measured plasma concentration profiles. Plasma concentrations of the major metabolite were lower than that of the parent drug. An average of 27% of the dose was found in urine as that metabolite. The effect on platelet swelling could be well characterized by a direct Emax model. The average concentration for half-maximum effect (IC50) was 12 ng/mL. Eniporide was found to have predictable linear pharmacokinetics in the investigated dose range. Platelet swelling time was shown to be a reproducible individual biomarker for pharmacodynamic activity, with great potential for a surrogate that predicts clinical outcome, since this effect is mediated through the same mechanism of action (NHE-1 inhibition) as the desired cardioprotective activity. Pharmacokinetic/pharmacodynamic modeling allowed a first estimate of the degree of NHE inhibition in the investigated dose range. PMID- 11210394 TI - Pharmacodynamic modeling of pantoprazole's irreversible effect on gastric acid secretion in humans and rats. AB - The relationship between the pharmacokinetics of pantoprazole, an irreversible proton pump inhibitor, and its effect on gastric acid secretion was evaluated in humans and rats. Pantoprazole pharmacokinetics were studied in 6 rats (5 mg/kg, i.v.) and 22 healthy volunteers (10 to 80 mg, i.v. and oral). Gastric acid secretion under maximum pentagastrin stimulation was measured after i.v. administration of placebo or pantoprazole in 31 rats (0.12 to 1.15 mg/kg) for 4 hours and in 31 subjects (20 to 120 mg) for 24 hours. Pantoprazole has short half lives of 0.5 hours in rats and 0.8 hours in humans. After administration of the highest dose, acid secretion was fully inhibited within 1 hour and for the whole observation period in both species. An irreversible pharmacodynamic response model was successfully developed and validated. The apparent reaction rate constants of pantoprazole with the proton pumps were 0.691 L/mg/h in rats and 0.751 L/mg/h in humans, and the apparent recovery rates of the pumps were 0.053 h 1 and 0.031 h-1, respectively. The maximum inhibition and the overall effect of pantoprazole are related to exposure, and the onset is related to initial pantoprazole concentrations. It was concluded that this irreversible response model accurately describes the effect of i.v. and oral pantoprazole on gastric secretion and may be used to predict effects under other dosage regimens. PMID- 11210395 TI - Theophylline metabolism after cardiac surgery. AB - The effect and metabolism of theophylline administration after cardiac surgery has never been reported. Two series of 2-hour intravenous aminophylline administrations (3 mg/kg/h) were conducted in 10 adult patients on the operative day (acute phase) and on the 4th or 5th postoperative day (recovery phase). Both blood and urine samples were collected for 24 hours after dosing. Heart rate increased in both phases, but the cardiac index increased with the decrease of diastolic blood pressure only in the acute phase (p < 0.05). Plasma concentration levels of theophylline tended to be slightly higher in the acute phase, and renal clearance increased in the recovery phase (p < 0.05). The urinary ratio of 3 methylxanthine to theophylline was significantly higher in the acute phase (p < 0.05). This suggests that cytochrome P4501A2 is partially activated rather than depressed and that N-demethylation is promoted more than hydroxylation immediately after surgery. PMID- 11210396 TI - Pharmacokinetic and pharmacodynamic modeling of NN703, a growth hormone secretagogue, after a single po dose to human volunteers. AB - The objective of this study was to describe the pharmacokinetics and pharmacodynamics of NN703, a growth hormone (GH)-releasing secretagogue, after po administration to healthy human male subjects. The study was designed as a randomized, placebo-controlled, double-blind, dose-escalating, single-dose trial of NN703 covering eight dose levels. Each of the dose levels had 6 subjects on active treatment and 2 subjects on placebo. NN703 was administered po as a solution. Blood samples for serum concentrations of NN703 and GH were collected before dosing and up to 24 hours after dosing. Serum concentrations of NN703 were determined using a validated analytical method, based on solid-phase extraction and LC/MS/MS detection. A two-compartmental model with zero-order input was used to describe the pharmacokinetics of NN703. The parameters of the elimination phase were fitted simultaneously, whereas the parameters describing the absorption phase were allowed to vary between the dose levels. The pharmacodynamics of NN703 was described by use of an indirect-response model containing both a threshold value and a modulator for the development of tolerance. It was concluded that the absorption of NN703 after po administration was nonlinear; the bioavailability increased with the dose. The serum concentration of NN703 required for half-maximal stimulation of GH was determined to be 485 ng/ml. The proposed indirect-response model requiring a threshold concentration and development of tolerance provided a useful mean of quantifying the effects of NN703. Furthermore, the development of tolerance shown based on pharmacokinetic/pharmacodynamic modeling of single-dose data presented here has been confirmed following multiple dosing in healthy male subjects. PMID- 11210397 TI - Pharmacokinetics of naratriptan in adolescent subjects with a history of migraine. AB - Naratriptan is a novel 5-HT1 agonist developed to treat acute migraine. The study objective was to characterize the pharmacokinetics of oral naratriptan in adolescent migraine patients outside a migraine attack. Subjects received a single 2.5 mg naratriptan tablet. Serial serum samples for naratriptan concentrations were collected over 24 hours. Blood pressure, pulse rate, and 12 lead ECG were recorded at baseline and at regular intervals after dosing. Seven patients--3 males and 4 females, 12 to 16 years of age--received drug and completed the study. The geometric mean and 95% confidence interval maximum concentration (Cmax) was 8.0 ng/mL (5.9-10.7), elimination half-life (t1/2) was 4.9 hours (4.5-5.4), area under the concentration-time curve (AUC) was 74.6 ng.h/mL (56.6-98.2), and apparent total clearance (Cl/F) was 558.8 mL/min (424.3 735.9). The median time to maximal concentration (tmax) was 4 hours, with a range of 1.5 to 4. Blood pressure, pulse rate, and ECG parameters did not change significantly from baseline. No serious adverse events or subject withdrawal after drug administration occurred. Oral naratriptan pharmacokinetic parameters in adolescents were similar to values reported in adults. Naratriptan doses for adolescents older than 12 years of age would be expected to be similar to adult doses. PMID- 11210398 TI - Effect of low- and high-fat meals on tacrolimus absorption following 5 mg single oral doses to healthy human subjects. AB - Tacrolimus (FK506, Prograf) is a macrolide lactone antibiotic widely used by the oral route for the prophylaxis of organ rejection in patients who have received allogenic liver or kidney transplants. This study investigated the influence of a high- versus a low-fat meal, relative to the fasting state (three treatments total), on the rate and extent of tacrolimus absorption following a single 5 mg oral dose. The protocol employed a three-period, randomized, crossover design employing 5 x 1 mg capsules in 15 healthy male nonsmoking, drug-free volunteers, 20 to 45 years of age, who were within 15% of their ideal body weight. Food had a clinically significant effect in reducing relative bioavailability, as well as slowing absorption, but did not affect terminal exponential half-life (approximately 34 hours). Mean maximum tacrolimus blood concentration (Cmax) values were 25.6, 5.88, and 9.03 ng/mL for the fasting, high-fat, and low-fat treatments, respectively; mean area under the blood concentration-time curve (AUC(0-infinity) values were 272, 181, and 201 (ng/mL)-h, respectively; and mean time of Cmax (tmax) values were 1.37, 6.47, and 3.20 hours, respectively. Differences in parameters between the fasting and each fed treatment were statistically significantly different (p < 0.05). Statistically significant differences also existed in tmax between the two meals. Results also indicated the safety of single 5 mg oral tacrolimus doses administered to healthy volunteers. PMID- 11210399 TI - The influence of food on the bioavailability of a twice-daily controlled release carbamazepine formulation. AB - Carbatrol, a new dosage form of carbamazepine (CBZ), was developed consisting of three different types of pellets (immediate release, controlled release, and enteric release). The objective of this study was to explore the influence of food on absorption of CBZ. This was a randomized, open-label, single-dose crossover study conducted in 12 healthy volunteers. Treatments were 2 x 200 mg Carbatrol with a high-fat meal, fasted, or sprinkled over applesauce (but otherwise fasted). Each subject received one dose of each treatment separated by a washout period of at least 2 weeks. CBZ bioequivalence was established based on the equivalence of AUC (extent of absorption) in all three conditions. Carbatrol may be taken with or without food or the capsule opened and sprinkled on food. PMID- 11210400 TI - Lack of effect of food on the pharmacokinetics of an extended-release oxybutynin formulation. AB - The effect of food on the pharmacokinetics of 15 mg oxybutynin XL was evaluated in a single-dose, randomized, crossover, open-label study in healthy volunteers. A validated, stereospecific, high-performance liquid chromatography assay was used to simultaneously determine the plasma concentrations of R- and S-oxybutynin and active metabolite R- and S-desethyloxybutynin. The mean AUC and Cmax values for each of the four analytes in the fed treatment were within +/- 20% of the fasting treatment values. The 90% confidence intervals for the treatment ratios (fed/fasted) for log-transformed Cmax and AUCinf values for the drug isomers and AUCinf values for the metabolite isomers were all within the 80% to 125% range. Only the ranges for the Cmax values for R- and S-desethyloxybutynin were slightly wider but were well within the 70% to 143% criteria recommended for Cmax when comparing effect of food. Lack of effect of food on oxybutynin XL is consistent with the previous observation that the osmotically controlled formulations are nearly insensitive to the gastrointestinal environment, including food. Oxybutynin XL was well tolerated, and the safety results were comparable whether administered alone or with food. In conclusion, oxybutynin XL administration does not require any caution to be exercised regarding food. PMID- 11210401 TI - Sevelamer hydrochloride (Renagel), a nonabsorbed phosphate-binding polymer, does not interfere with digoxin or warfarin pharmacokinetics. AB - Sevelamer hydrochloride (Renagel) is a nonabsorbed phosphate-binding polymer marketed for the treatment of hyperphosphatemia in adult patients receiving hemodialysis. Sevelamer also exhibits bile acid-binding properties resulting in LDL cholesterol lowering. Potential drug interactions between digoxin and warfarin and sevelamer were studied. These two drugs were chosen because they are known to bind to the bile acid-binding polymers, cholestyramine and colestipol. Studies were single dose, crossover, with or without six 2.4 g doses of sevelamer. Plasma concentrations were determined using validated analytical methods. The pharmacokinetic profiles of digoxin and warfarin were not altered by the simultaneous and continued administration of sevelamer. Values for the ratio of ln[AUC(0-infinity)], ln[AUC(0-t)], and ln[Cmax] with and without sevelamer were close to 100%, and the 90% confidence intervals for these ratios were within the 80% to 125% range. It was concluded that sevelamer does not interfere with the absorption or excretion of digoxin or warfarin. PMID- 11210402 TI - Sevelamer hydrochloride (Renagel), a phosphate-binding polymer, does not alter the pharmacokinetics of two commonly used antihypertensives in healthy volunteers. AB - Sevelamer hydrochloride (Renagel) is a nonabsorbed phosphate-binding polymer approved for the treatment of hyperphosphatemia in adult hemodialysis patients. The authors studied the potential effect of sevelamer on the pharmacokinetics of two antihypertensive drugs, enalapril (20 mg) and metoprolol (100 mg), commonly used in end-stage renal disease patients. Two studies were conducted. Both were single dose, crossover design with or without a 2.4 g dose of sevelamer in healthy volunteers. Within each study, there was a 7-day washout interval between the two dose administrations. There were 28 volunteers in the enalapril study and 32 in the metoprolol study. The mean plasma concentrations versus time profiles of enalapril, enalaprilat, and metoprolol were not altered by the simultaneous administration of sevelamer. Values for the ratio of ln[AUC(0-infinity)], ln[AUC(0-t)], and ln(Cmax] with and without sevelamer were approximately 100%, and the 90% confidence intervals for the ratios of these parameters with and without sevelamer were within the 80% to 125% range in all cases except for the ln[Cmax] of enalapril, which had an upper confidence bound of 125.4%. The authors conclude that sevelamer does not interfere with the absorption and elimination of enalapril and metoprolol. PMID- 11210403 TI - Lack of interaction between levofloxacin and oxycodone: pharmacokinetics and drug disposition. AB - Previous studies have demonstrated a significant reduction in the oral bioavailability of trovafloxacin and ciprofloxacin when administered concomitantly with an intravenous opiate such as morphine. This decrease in absorption results in a 36% and 50% lower AUC for trovafloxacin and ciprofloxacin, respectively, which could cause clinical failures. The authors investigated the possibility of a similar interaction between oxycodone and levofloxacin. Eight healthy volunteers were randomized in an open-label, two-way crossover study to receive oxycodone, 5 mg p.o. Q4H, and levofloxacin, 500 mg p.o. 1 hour after starting the oxycodone or levofloxacin 500 mg p.o. alone. Blood samples were drawn at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours for Cmax, tmax, and AUC determinations. There was not a significant difference (p > 0.05) in AUC (48.59 +/- 8.52 vs. 49.9 +/- 9.93), Cmax (7.73 +/- 2.6 vs. 6.6 +/- 2.0), and tmax (1.1 +/- 0.6 vs. 1.6 +/- 1.1) for levofloxacin versus levofloxacin/oxycodone regimens. It was concluded that oral oxycodone and levofloxacin can be administered concomitantly without a significant decrease in AUC, Cmax, or tmax. PMID- 11210404 TI - Lack of an effect of azithromycin on the disposition of zidovudine and dideoxyinosine in HIV-infected patients. AB - Two studies were conducted in HIV-infected subjects to assess the potential for azithromycin to interact with zidovudine and dideoxyinosine. Both studies used 12 subjects. The zidovudine study dosed subjects with 1200 mg/day of azithromycin (n = 7) (later changed to 600 mg/day [n = 5]) for Days 8 to 21 of a 21-day course of 100 mg, five times/day of zidovudine. Subjects treated with 200 mg of dideoxyinosine twice daily for 21 days received 1200 mg of azithromycin or an equivalent amount of placebo/day for Days 8 to 21. Antiretroviral plasma and urine sampling were conducted on Days 1, 7, and 21 for zidovudine and on Days 7 and 21 for dideoxyinosine. Peripheral mononuclear cells were also collected for quantitation of phosphorylated zidovudine. Azithromycin had no significant impact on the Cmax and AUC of zidovudine, although it significantly decreased the zidovudine tmax by 44% and increased the intracellular exposure to phosphorylated zidovudine by 110%. Azithromycin had no significant effect on dideoxyinosine pharmacokinetics. Based on the results of these studies, it is concluded that azithromycin may be safely coadministered with both zidovudine and dideoxyinosine. PMID- 11210405 TI - Evaluation of the potential pharmacokinetic interaction between almotriptan and fluoxetine in healthy volunteers. AB - This study was designed to assess the pharmacokinetics of almotriptan, a 5HT1B/1D agonist used to treat migraine attacks, when administered in the presence and absence of fluoxetine. Healthy male (n = 3) and female (n = 11) volunteers received (1) 60 mg fluoxetine daily for 8 days and 12.5 mg almotriptan on Day 8 and (2) 12.5 mg almotriptan on Day 8, according to a two-way crossover design. Plasma and urinary almotriptan concentrations were measured by HPLC methods. Treatment effects on pharmacokinetic parameters were assessed by analysis of variance. Mean almotriptan Cmax was significantly higher following combination treatment with fluoxetine (52.5 +/- 11.9 ng/ml vs. 44.3 +/- 10.9 ng/ml, p = 0.023). Mean AUC0-infinity was not significantly affected by fluoxetine coadministration (353 +/- 55.7 ng.h/ml vs. 333 +/- 33.6 ng.h/ml, p = 0.059). Confidence interval analysis (90%) of log-transformed pharmacokinetic parameters showed that the confidence interval for AUC0-infinity was within the 80% to 125% limit for equivalence, but Cmax was not (90% CI 106%-134% of the reference mean). Adverse events were mild to moderate in intensity, and no clinically significant treatment effects on vital signs or ECGs were observed. The results show that fluoxetine has only a modest effect on almotriptan Cmax. Concomitant administration of the two drugs is well tolerated, and no adjustment of the almotriptan dose is warranted. PMID- 11210406 TI - Visual hallucination and tremor induced by sertraline and oxycodone in a bone marrow transplant patient. AB - The authors report a case of probable serotonin syndrome caused by the coadministration of sertraline and oxycodone. A 34 year-old male patient experienced visual hallucinations and severe tremor after dramatically increasing his dosage of oxycodone while on stable amounts of sertraline and cyclosporin. Discontinuation of cyclosporin did not result in resolution of his symptoms. Consideration of a possible sertraline-oxycodone interaction led to withholding sertraline, which resulted in symptom resolution. Serotonin syndrome has been noted with sertraline in combination with other drugs, but this is the first report in combination with a narcotic analgesic. Possible pharmacological mechanisms are discussed. In complicated patients that are taking multiple medications, physicians should be aware of this possible interaction to avoid delay in the diagnosis of serotonin syndrome. PMID- 11210407 TI - [Composition of circulating immune complexes in acute toxoplasmosis]. AB - The circulating immune complexes (CIC) that form in the hot just in early Toxoplasma gondii invasion can be present in the blood bed for a while. At the same time, the data on the antigenic composition of CIC in toxoplasmosis are fragmentary and rather contradictory. The investigation used enzyme immunoassay (EIA) to detect specific CIC that contain antigens to T. gondii tachyzoites in the sera of different populations and studied their antigenic composition by immunoblotting after 2-6% polyethylene glycol 6000-induced deposition. Examining 464 sera from groups of individuals with varying-stage T. gondii invasion indicated CIC in each, but showing their different frequency. CIC were virtually present in all sera from children who had been diagnosed as having congenital toxoplasmosis. In groups of seropositive pregnant women, CIC detection rates were noticeably higher in the samples showing both IgG and IgM antibodies (40.2 and 66.4%, respectively). CIC were also revealed in 9.8% of the seronegative blood donors; however, immunoblotting failed to confirm that they had no components that specifically reacted with T. gondii tachyzoite antigen antibodies. There were some differences in the composition of CIC in the serum yielding positive results in both EIA and immunoblotting. The serum CIC from pregnant women that exhibited only IgG antibodies contained mainly T. gondii antigens having molecular weights of 67 and 30 kD. The serum CIC from children with congenital toxoplasmosis and from pregnant women with serologically detected IgM antibodies to Toxoplasma antigens were found to contain 55-58-, 48-, 44-, 38-, 30-, and 26 kD components. The same molecular weight proteins were detected by electrophoretic studies of Toxoplasma excretory-secretory antigen (ESA). Comparing the findings suggests that in acute toxoplasmosis, the circulating complexes mainly contain ESA of the tachyzoites which appear in human blood just at the onset of invasion. Thus, this study demonstrates that specifically CIC are detectable in the sera of individuals infected with T. gondii and their antigenic composition varies with the stage of disease. In the authors' opinion, the detection of specific CIC and the determination of their antigenic composition may be serve an additional test in diagnosing acute toxoplasmosis. PMID- 11210408 TI - [Phenotypic variability in P. vivax with short- and long-term incubation period]. AB - The combined transmission of P. vivax phenotypes was studied. The phenotypes were determined by the duration of a latent parasitic development stage by comparing the intervals from first manifestations of malaria with short- and long-term incubations to its relapse. The study used data on 2493 patients treated with chloroquine (900 mg base for adults) alone at follow-ups in the North-Eastern Delhi (India) in 1988-1992. The combined transmission of P. vivax phenotypes was shown to differ in malaria with short- and long-term incubation. The P. vivax phenotype with manifestations on an average a year following infection in patients with mainly short-term incubation malaria and that with manifestations on an average year and a half after infection in a group of patients with primary long-term incubation malaria were significantly more frequently. Long-term incubation malaria shows simultaneously a larger number of phenotypes than does short-term incubation one. Patients with long-term incubation malaria display a combination of 2 phenotypes (6%) significantly less frequently than that of 3 different phenotypes or more (17%). The similar combinations were observed in the equal number of patients with short-term incubation malaria (7%). PMID- 11210409 TI - [Adaptive property of hantaviruses during their isolation from cultured VERO-E6 cells in relation to the type of the ecological host]. AB - As a result of virological studies, 185 lung tissue specimens from 4 rodent species caught near Khabarovsk were isolated and fixed in the passages of cultured Vero-6 cells of 68 hantavirus strains. The capacity of the strains to adapt to the cells was assessed by using the adaptive index involving the mean rates of successful isolation, its duration, hantavirus antigen titer in the material used for infection. The strains of hantavirus serotypes were noted for the highest adaptive properties, which are ecologically associated with rodents of the family Mus, such as field and East-Asiatic mice. Lower adaptive capacities were established for the strains of hantavirus serotypes, which are ecologically related to rodents of the family Cricetidae, such as large and large-toothed redback voles. The differences found in the adaptive capacities of hantavirus strains cultured in Vero-E6 cells reflect the degree of specialization of some hantavirus serotypes to particular host rodent species during their long-term coevolution. PMID- 11210410 TI - [Duration of the larvicidal effect of spore crystalline mass of bacteria Bacillus thuringiensis spp. israelensis and Bacillus sphaericus in the laboratory setting]. AB - The duration of action of sporocrystalline mass of Bacillus thuringiensis spp. Israelensis (Bti) and Bacillus sphaericus (Bsph) against three-age larvae of An. stephensi mosquitoes was studied in the laboratory setting. The duration of action depends on its initial concentration. The optimal concentration should be at least 10(5) spores/ml for An. stephensi larvae. Decreasing the concentration reduces the duration of larvicidal action. Increasing the number of the larvae placed also diminishes the duration of action shown by Bti. This has no significant influence on the duration of action by Bsph. The presence of dead larvae in the test vessel increases the duration of action by Bti only by 4 times whereas Bsph acts rather long. The follow-ups lasted 60 weeks with full death of the larvae placed again. A significant water resistance of Bti sporocrystalline mixture was found. The mixture retained its larvicidal activity 6 months following its presence in the dechlorinated water without larval placement. Bsph was less resistant and its complete inactivity was noted under the same conditions just following 2 months. PMID- 11210411 TI - [Homeopathic preparation Cheblin-CK-1 in the pathogenetic therapy of echinococcosis]. AB - This study was experimental and clinical. The experiments were made on 80 cotton rats. The clinical study covered 289 patients operated on for echinococcosis. Earlier studies indicated that echinococcosis is accompanied by secondary immunodeficiency and amino acid metabolic disorders. The homeopathic drug Cheblin CK-1 used normalized amino acid metabolism 40 days after treatment in these patients. The same properties were displayed by homeopathic drugs. PMID- 11210412 TI - [Improving the sanitary and epidemiologic surveillance system is a necessary condition for enhancing the efficiency of preventive measures against parasitic diseases]. AB - The paper presents a pattern of the improved sanitary and epidemiological surveillance system against parasitic diseases in Russia at the present stage. A great deal of species of causative agents of parasitic diseases, a great variety of ways and factors of their transmission show that there is a need for its further optimization by taking into account local, natural, climatic and social conditions of the population's life and activities and paying a particular attention to the system's key point, namely to the evaluation of the risk of infection, which is the basis of planning preventive measures against parasitic diseases. PMID- 11210413 TI - [Testing CK group preparations in hymenolepiasis in white mice]. AB - The drugs CK-1 and CK-2 are a kerosene milky-stage walnut (Juglans spp.) extract. The drugs CK-3, CK-4, and CK-5 are derived from monkshood (Aconitum) roots, garlic (Allium sativum), and Ferula, respectively. Albino mice were infected with hymenolepiasis by the procedure of B.A. Astafyev et al. (1989). The mice were aged 3 weeks, weighed 7-8 g, and spontaneous invasion-free. The doses of 25 to 100 mg/kg were tested. The antihelminthic effects of the extragent of the drugs- aircraft kerosine purified by the authors' procedure--were additionally examined. The purified aircraft kerosine was found to have moderate antihelminthic effects, but failed to provide 100% antihelminthic activity when given even in very high doses (500 mg/kg or more). The drug CK-1, 100 mg/kg, completely eliminated hymenolepiasis in the experimental animals. Other drugs CK-3, CK-4, and CK-5 used in doses of 100 mg/kg body weight failed to provide 100% antihelminthic efficiency. PMID- 11210415 TI - [Ecological and epizootic characteristics of various zonal types of natural reservoirs of alveococcosis in the Omsk region]. AB - Natural foci of alveococcis of various zonal types were found in the Omsk region. The final pathogen hosts are red (aspen and birch forests, northern and southern forest-steppe, steppe) and corsac (southern forest-steppe and steppe) foxes and, perhaps, wolves (southern taiga). There are intermediate hosts, that are small mammals of 10 species, among which Clethrionomys voles (northern redbacked, large toothed redbacked, and bank voles in the southern taiga; northern redbacked voles in the aspen and birch forests and northern forest-steppe), root ones (in the northern and southern forest-steppe, and steppe), narrow-skulled ones and house mice (in the southern forest-steppe and steppe) are of the greatest epizootological significance. The seasonal and biotopical dynamics of the spatial pattern of a natural alveococcis foci was established in the subareas of the south taiga and northern forest-steppe. PMID- 11210414 TI - [Clinical and epidemiological characteristics of hymenolepiasis in the Ivano Frankovsk region]. AB - Based on their retrospective epidemiological analysis and examination of 56 outpatient case histories, the authors have studied the clinical and epidemiological regularities of hymenolepiasis in the Ivano-Frankovsk region, which is characterized by: 1) its epidemic and familial pattern, mainly afflicting rural populations, young schoolchildren in particular; 2) high contagiousness and incidence of multiinvasions in the tense foci; 3) a number of the most typical syndromes identified in the clinical picture of helminthic infections, which may serve as criteria for selecting patients for laboratory studies. PMID- 11210416 TI - [Sensitivity of malaria mosquito larvae to bacterial insecticides in relation to handling]. AB - The conditions for cultivation of malaria mosquito larvae were found to exert a great impact on their sensitivity to bactoculicide. Elevating keeping temperatures for An. sacharovi and An. pulcherrimus by 10-11 degrees C causes 2-4 fold increases in LC50. There are virtually no impacts of larval population during their development or temperature-population density relationships. Ten fold increases in larval population density under which An. stephensi larvae have been grown result in 3-fold decreases in LC50. There are no impacts of temperatures and temperature-population density relationships either. There are also great larval species-specific differences in their sensitivity to bactoculicide. PMID- 11210417 TI - [Characteristics of the course of intestinal amebiasis concurrent with other diseases]. PMID- 11210418 TI - [Borrelia infection in Ixodes ticks in the Cheliabinsk region]. PMID- 11210419 TI - [Further study of the circulation of arboviruses in the Astrakhan region (1998 1999)]. PMID- 11210421 TI - [Detection of pentastomes in Russia]. PMID- 11210420 TI - [Epidemic leptospirosis outbreaks caused by leptospires of Pomona serological group in the Altai region]. PMID- 11210422 TI - [Organ pathology in chronic tissue-dwelling helminthic infections: role of blood and tissue eosinophilia, immunoglobulinemia E, G4, and immune response-inducing factors]. AB - The results of earlier clinical, pathomorphological, and immunological studies of organic visceral and tissue lesions in helminthic infections [2, 3, 8, 10, 11, 14, 46] and present clinical and immunological ones [4-6, 44, 45] were analyzed and discussed in the light of a fundamental literature data review. The chronic visceral pathology in tissue-dwelling helminthic infections is associated with super- and reinfections [1, 2, 16, 36], with an inadequate immune response of humans to the invasion of zoonotic agents [2, 6, 13, 20] and with an individual invalidity of an immune response to infections [1, 2, 6, 16, 54]. The persistent course of infections, especially zoonotic, leads to organic pathology, sometimes irreversible [2, 13, 15, 21, 34, 46] if an individual (population) does not respond by immunity or by acquired (inherited) tolerance of invasion [1, 2, 3, 11, 16, 20, 36]. Transplacental transfer of Opisthorchis felineus antigens in the hyperendemic foci of the infection does not prevent superinfections, but does prevent the acute phase of disease and significantly mitigates the organic lesions in the chronic phase in spite of a very high intensity of infection [7, 10, 11]. Paramyosines (Pmes), proteins expressed on the tegument of Schistosoma mansoni and S. japonicum, show their immunogenic effect [42]. Antibodies to PM of Lumbricoidea and to a cardiac muscle myosin peptide (alpha-mp), known to induce experimental allergic myosites [55], were revealed in the sera of 32 trichinellosis, toxocarosis, opisthorchiasis, and hydatid echinococcosis patients with organic visceral abnormalities. The levels of antibodies against alpha-mp correlated with the severity of pathology [44]. S. mansoni PM peptide smp97 is a homologue of alpha-mp [25]. This fact suggests that there is a relationship between the development of an immune response to Pmes immunological processes in helminthiases. The relationship between organic visceral pathology and a competitive with serum IgE serum IgG4 hyperproduction at the early [6] and late stages of the studied helminthic infections was revealed. One may resume that this balance of production of these isotypes is not beneficial for the development of disease as IgG4-antibody hyperproduction is not beneficial for reinfection resistance [26, 28, 54]. One of the mechanisms may be serum IgG4 blocking the antibody-dependent cytotoxic effect, as it was supposed for unspecific IgE hyperproduction [47]. The selected development of cardiomyopathy or obstructive fibrosis in the lung after trichinellosis [2, 6, 45], endomyocardiofibrosis in the foci of filariases [21, 31] suggests that their development like resistance or susceptibility to infections [54] should be programmed. PMID- 11210423 TI - George Austin, MD. PMID- 11210424 TI - Intra-ischemic hypothermia attenuates intercellular adhesion molecule-1 (ICAM-1) and migration of neutrophil. AB - Adhesion of neutrophil to the endothelium and subsequent transmigration has been reported to contribute to progression of focal ischemia. Hypothermia has been known to attenuate ischemic insult through various mechanisms of action. The authors evaluated the effect of hypothermia on expression of intercellular adhesion molecule-1 (ICAM-1) protein and on transmigration of neutrophil with immunohistochemical method. Transient focal ischemia model in rats was employed, and animals received 2 h of either normothermic or hypothermic ischemia. To confirm the effectiveness of hypothermia on neuroprotection, cortical infarct area was compared between the two groups. Our results demonstrated that hypothermia reduced both the number of microvessels expressing ICAM-1 and that of neutrophils migrating into ischemic tissue. Comparison of cortical infarct area showed persistent protective effect. This study indicates that reduction of ICAM 1 expression and subsequent reduction of migrating neutrophil in hypothermia can contribute to attenuation of ischemic damage. PMID- 11210426 TI - The influence of ruptured cerebral aneurysm localization on the blood flow velocity evaluated by transcranial Doppler ultrasonography. AB - The relationship between changes of blood flow velocities in cerebral arteries measured by transcranial Doppler ultrasonography and aneurysm localization was investigated in a group of 165 patients after aneurysmal subarachnoid hemorrhage (SAH). Mean blood flow velocities (MFV) in the middle cerebral artery (MCA) and anterior cerebral artery (ACA) were registered. In patients with aneurysm of internal carotid artery and MCA (group A) statistically significant higher values of MFV from the 1st to the 5th day and on the 12th, 13th, 14th, 15th, and 19th day after SAH were found compared to patients with aneurysm of the anterior communicating artery, ACA, and pericallosal artery (group B). Pathological values of MFV exceeding 120 cm sec-1 in MCA were registered during 14 days in group A and during eight days in group B. Blood flow velocities in ACA were statistically significantly higher in group B on the 2nd, 7th, 9th and 11th day compared to group A. Pathological values of MFV exceeding 90 cm sec-1 in ACA were registered during nine days in both groups. MFV differences between group A and group B in 38 patients subjected to delayed surgery were not observed. The influence of aneurysm localization was observed between the 7th and 14th day after SAH. Critical MFV values for vasospasm in the MCA should be 120 cm sec-1 and in the ACA 90 cm sec-1. PMID- 11210425 TI - Neurotransmitter distribution in the second trimester fetal human corpus striatum. AB - One experimental strategy that may offer hope in the neurodegenerative disorder Huntington's disease (HD) has been neural transplantation. In HD, most of the pathological changes occur in the corpus striatum. Fetal human striatal implants will most likely be the first transplant strategy attempted in clinical trials to replace lost neurons and/or prevent the degeneration of neurons destined to die. The temporal expression of neurotransmitters in the developing human corpus striatum is a key factor in determining the optimum age of transplantable tissue. To this end, an immunocytochemical analysis of various neurotransmitters was performed on second trimester human brains. Antibodies against acetylcholine, gamma-aminobutyric acid, enkephalin, neuropeptide-Y and substance P were used in ten human fetal brains ranging from 13 to 21 weeks gestation. The presence and pattern of distribution for these neurotransmitters varied in the different parts of the corpus striatum (globus pallidus, putamen, caudate nucleus). These results are compared to the already existing data for the adult human corpus striatum. PMID- 11210427 TI - Magnetoencephalographic investigation of somatosensory homunculus in patients with peri-Rolandic tumors. AB - In order to investigate functional topography of the hand somatosensory cortex in five patients with peri-Rolandic tumors (four frontal lobes and one parietal lobe), we recorded somatosensory evoked fields (SEFs) using magnetoencephalography (MEG) after stimulation of the median nerve (MN) and the five digits. The results obtained were compared with those of five normal healthy subjects. In all five patients, SEFs following MN and digit stimulation showed the previously described respective N20m and N22m components of primary sensory response. Single dipole modeling was applied to determine the three dimensional cortical representations of the N20m and N22m components. The cortical representations of the hand were identical to those of normal subjects, arranging in an orderly somatotopic way from lateral inferior to medial superior in the sequence thumb, MN, index, middle, ring, and little fingers. This sensory homunculus was confirmed by cortical recording of the somatosensory evoked potentials (SEPs) at the time of surgery. Thus, we demonstrate that SEFs, recorded on MEG in conjunction with source localization techniques, are useful to non-invasively investigate the functional topography of the human hand somatosensory cortex in pathological conditions. PMID- 11210429 TI - Influence of acupuncture upon expressing levels of basic fibroblast growth factor in rat brain following focal cerebral ischemia--evaluated by time-resolved fluorescence immunoassay. AB - We investigate the expression of basic fibroblast growth factor (bFGF) during ischemia-reperfusion with or without electroacupuncture (EA) treatment, and observe the effect of EA on ischemic cerebral injury. In the present study, a sensitive sandwich time-resolved fluoroimmunoassay (TR-FIA) method was developed to quantitatively analyze the levels of bFGF in rat brain. The results indicated that the obvious cerebral infarction and swelling were observed after ischemia reperfusion, and the opening amount of cerebral blood micrangium was increased. In the meantime, the expression of bFGF was also improved in striatum and frontoparietal cortex. EA alleviated the ischemic injuries induced by MCAO and markedly upregulated the opening amount of the micrangium. Owing to application of EA, the expression of bFGF was notably enhanced in striatum and cortex. The results give us some hints for the neuroprotective mechanism of EA, that is, EA may partially exert protective effects on neurons through regulating the blood dynamics and the endogenous expression of bFGF. PMID- 11210428 TI - GABAA receptor antisense epilepsy: histological changes following infusion of antisense oligodeoxynucleotide to GABAA receptor gamma 2 subunit into rat hippocampus. AB - A deficiency of neuronal inhibition mediated by gamma-aminobutyric acid (GABA) via the GABAA receptor complex has been hypothesised to be a central factor in epileptogenesis. Intrahippocampal infusion of antisense oligodeoxynucleotide (ODN) to the GABAA receptor gamma 2 subunit in rats leads to electrographic limbic status epilepticus. In this model, epileptic phenomena are accompanied by loss of hippocampal neurones. The purpose of the present study was to investigate the time-course of morphological changes following hippocampal antisense 'knockdown' of the GABAA receptor gamma 2 subunit. gamma 2 subunit antisense ODN was infused continuously into the right hippocampus for periods between 1 and 5 days. After about 4 days of infusion, pronounced neurodegenerative changes were consistently observed within the ipsilateral hippocampus. In general, marked loss of CA3 pyramidal cells was found. The notion that the histological changes induced by the antisense ODN were specific to the applied ODN sequence was supported by the finding that a mismatch control ODN did not induce neurodegenerative changes, except for a small lesion in the immediate vicinity of the infusion site. Extensive ipsilateral hippocampal infiltration with monocytes and macrophages was a feature of antisense ODN infusion, but was considerably less pronounced after the infusion of control ODN. Immunocytochemistry using an antibody labeling glial fibrillary acidic protein (GFAP), revealed marked astroglial hypertrophy/proliferation after 4 days of antisense treatment, i.e., coincident with the development of neurodegeneration, in the ipsilateral hippocampus. At this time GFAP-immunoreactivity was also evident in the contralateral hippocampus, indicating contralateral spread of seizure activity. PMID- 11210430 TI - Approaches to the sellar and parasellar region: anatomic comparison of endonasal transsphenoidal, sublabial-transsphenoidal, and transethmoidal approaches. AB - Various surgical approaches have been described for treating lesions which arise in the sellar region. The popular transnasal-transsphenoidal and transethmoidal transsphenoidal approaches avoid the morbidity associated with transcranial operations while allowing enough exposure to successfully remove most lesions that arise in and around the sella. The goal of the present study was to accurately quantify the amount of exposure to the sellar and suprasellar region that the transethmoidal-transsphenoidal, endonasal-transphenoidal, and sublabial transsphenoidal approaches provide. Each of the three approaches was performed on 14 formalin fixed heads with the aid of the operative microscope. The distances of relevant surgical landmarks, and the amount of exposure superior and anterior to the dorsum sella as well as the lateral exposure obtained through each of these approaches was carefully recorded. The mean distances were then used to calculate the volume of exposure offered by each approach. It was found that the sublabial-transsphenoidal approach afforded the greatest volume of exposure superior and anterior to the dorsum sella. The endonasal-transsphenoidal and the transethmoidal approaches were both found to offer less suprasellar volume exposure, with the transethmoidal approach offering the least. The authors believe the information obtained through this study illustrates some important anatomical relationships which can be used to advantage by the surgeon to tailor the most appropriate approach, depending upon the precise location of the lesion either within the sella or suprasellar region. PMID- 11210431 TI - Dynamic cerebral autoregulation testing as a diagnostic tool in patients with carotid artery stenosis. AB - Evaluation of dynamic cerebral autoregulation might yield a physiologically more adequate measure of cerebral hemodynamic impairment in carotid artery stenosis than CO2-reactivity. This study re-evaluates and compares the Valsalva maneuver (VM) and phase shift during deep breathing. Nineteen patients with severe carotid artery stenosis and 17 age-matched controls were examined using transcranial Doppler sonography and non-invasive blood pressure recordings (Finapres). Phase shift was determined by cross-spectral analysis, responses to VM were graded by the formerly-introduced autoregulation slope index (ASI) and the new Valsalva time index (VTI). Phase shift and autoregulatory indices were significantly reduced on the affected side (p < 0.001). Correlations with CO2-reactivity were significant when pooling values of controls and patients (r from 0.54 to 0.78; p < 0.001). Correlations except for the VTI (r = -0.65; p = 0.002) were not significant considering only the affected side in patients. Correlations of pooled values between phase shift and VM-derived indices were significant (VTI r = -0.62; p < 0.001; ASI r = 0.49; p < 0.001), within patients only when comparing side-to-side differences (VTI r = -0.58; p = 0.009; ASI r = 0.52; p = 0.023). In conclusion, detection of impaired cerebral autoregulation is possible both by deep breathing and VM. The new VTI seems to be more suitable than the conventional ASI. Inter-method agreement concerning the extent of impairment is only acceptable for intra-individual side-to-side differences. Since absolute values of one autoregulation testing method or CO2-reactivity alone might fail, various tests should be combined for comprehensive assessment of cerebral hemodynamic impairment. PMID- 11210432 TI - Clinical application of an ultrasonically activated scalpel in neurosurgery. AB - Ultrasonically activated scalpel (UAS) is a surgical device utilizing ultrasonic energy to cut and coagulate tissues simultaneously. The actions and features of UAS are considerably different from those of conventional ultrasonic cavitational aspirators (UCA) that have been used frequently in the neurosurgical field. The UAS has been used routinely in a number of general surgeries, including laparoscopic surgeries and open surgeries of the lung and liver. However, neurosurgical application of UAS has not been reported. We used UAS in surgical resection of intracranial tumors consisting of five meningiomas, two gliomas, and one metastatic brain tumor, and monitored thermal changes in tissues using thermoencephaloscopy to investigate the possibility of heat injury by UAS. It was used to achieve both dissection of the attachment of meningiomas and internal decompression of the tumors and allowed efficient resection of various tumors with minimal bleeding by adjustment of the combination of coagulation and cutting powers at five different positions. The attachment of meningiomas was coagulated and cut easily and safely by UAS. Moreover, infrared thermographic study showed that the degree of temperature increase and the area of elevated temperature were extremely limited in UAS. The current study suggests that it is a promising device in neurosurgery. PMID- 11210433 TI - Reduction cranioplasty for craniocerebral disproportion due to chronic subdural hematoma in infants. A technical report. AB - Advanced craniocerebral disproportion due to chronic subdural hematoma in infants which is resistant to conventional treatments requires reduction cranioplasty as the last resort. The present paper deals with our experience with two such cases originated from head injury. Since the volume of the hematoma cavity was calculated based on the pre-operative CT scans, we devised a mathematical formula to design how the cranial vault could be reconstructed for reduction. This enabled us to pre-determine the extent of cranial reduction which was tailored to each patient. Furthermore, the present methodology is characterized by the modification that the midline bone strip overlying the superior sagittal sinus was shortened at its anterior end and bent down using the posterior end as a hinge. Since the follow-up results were favorable, this technique of reduction cranioplasty is reported in detail. PMID- 11210434 TI - The neurochemical basis for the applications of the greater omentum in neurosurgery. AB - The omentum has been utilized in neurosurgery for over 30 years. However, the anatomical and physiological bases for its applications have not been described in great detail. In this paper, we will review the current status of the omentum applications for the management of central nervous system disorders. PMID- 11210435 TI - L-selectin inhibition does not reduce injury in a rabbit model of transient focal cerebral ischemia. AB - Neutrophils are known to mediate injury in acute ischemic stroke especially during reperfusion. Migration of neutrophils into regions of ischemic injury involves binding to the endothelial cells via interactions with various adhesion molecules. One adhesion molecule, L-selectin, is found on the surface of leukocytes, and is shed prior to leukocyte infiltration. We studied whether a humanized antibody to L-selectin (HuDREG200) might limit ischemic injury in an experimental stroke model. New Zealand White rabbits underwent transorbital occlusion of the left middle cerebral, anterior cerebral and internal carotid arteries using aneurysm clips for 2 h followed by 6 h of reperfusion. Treatment with a saturating dose (4 mg kg-1) of HuDREG200 (n = 8) or vehicle (n = 8) was administered 20 min after occlusion and given as a single i.v. bolus. Hemispheric ischemic neuronal damage (IND) as seen on hematoxylin and eosin stained sections was no different between groups (HuDREG200, 23.3% +/- 6%; vehicle, 19.6% +/- 6%; mean +/- SEM, n.s., t-test). Immunohistochemical staining with neutrophil elastase confirmed the presence of neutrophils within regions of IND in control brains, but treatment did not alter their numbers within ischemic tissue. We conclude that antagonism of neutrophil adhesion at the level of L-selectin does not alter ischemic injury in experimental stroke. PMID- 11210436 TI - Glutamate enhances DNA fragmentation in cultured spinal motor neurons of rat. AB - The role of glutamate in the mechanism of spinal motor neuron death is not fully understood. With addition of glutamate to primary culture of 11-day-old rat spinal cord, terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) positive nuclei were found in spinal large motor neurons from 24 h, and the number of TUNEL positive large motor neurons greatly increased at 48 h. In contrast, only a small number of large motor neurons became TUNEL positive at 48 h with addition of vehicle to the primary spinal cord culture. The present results show that excessive amount of glutamate enhances DNA fragmentation in developing large motor neuron of cultured spinal cord by involving in apoptotic process of the neurons. PMID- 11210437 TI - Spatial and temporal distribution of Bax in rat spinal cord during normal aging. AB - Amytrophic lateral sclerosis is characterized by relentlessly progressive degeneration of spinal cord motor neurons. During the disease, the bcl-2 family genes have been reported to alter their expression levels. To understand the meaning of these changes, the expression pattern of Bax in rat spinal cord and its changing pattern during normal aging were investigated by immunohistochemical staining. Spatial expression of the protein showed a diffuse distribution pattern with immunoreactivity more prominent in the anterior hom. With advancement of age, the cell densities of Bax-positive cells tended to increase. The increasing expression of Bax might be positively associated with amyotrophic lateral sclerosis. This work demonstrates for the first time how Bax expression changes in rat spinal cord during normal aging. PMID- 11210439 TI - Fluid loading in rats increases serum brain natriuretic peptide concentration. AB - Hyponatremia after subarachnoid hemorrhage has been linked to high plasma concentration of atrial natriuretic peptide and brain natriuretic peptide. Volume expansion therapy to prevent symptomatic vasospasm, such as intensive hypertensive and hypervoremic therapy, may alter systemic concentration of these peptides. We therefore examine brain natriuretic peptide secretion in rats in response to acute volume expansion, infusing to 10 ml of saline over 1 h. In the 10 ml group, brain natriuretic peptide concentrations showed a significant increase from pre-infusion concentrations 1 h after initiation of infusion, but had begun to fall 1 h later. We suspect that high plasma concentration of brain natriuretic peptide after subarachnoid hemorrhage is partly caused by hypervoremic therapy. PMID- 11210438 TI - Metabolic alterations in cerebrospinal fluid from double hemorrhage model of dogs. AB - Even though cerebral vasospasm after subarachnoid hemorrhage (SAH) causes cerebral ischemia or infarction, the metabolic alterations in cerebrospinal fluids (CSF) after SAH have not been studied. This study was undertaken to measure the levels of glucose, lactate, pyruvate and glutamate in CSF from double hemorrhage dog models. Thirty-two mongrel dogs of either sex, weighing 18-24 kg, underwent double hemorrhage by percutaneous needle puncture of the cistema magna and injection of autologous blood on day 0 and day 2. The dogs were then sacrificed on day 3, 5 and 7, after collecting CSF. In another study, the dogs were treated with mitogen-activated protein kinase (MAPK) inhibitors PD98059 and U0126, and caspase-2 and caspase-3 inhibitors from day 3 to day 6 after initial blood injection. CSF was collected on day 7 before dogs were sacrificed. The concentration of glucose, lactate, pyruvate and glutamate in CSF was measured by photometrical method. Compared with CSF collected on day 0, glucose was decreased on days 5-7, lactate was increased on days 2-7, pyruvate was increased on days 2 7, and glutamate was increased on days 3-7 (p < 0.05). In the groups treated with MAPK or caspase inhibitors, most of the metabolic alterations remained unchanged as compared with CSF from untreated dogs. Clinically, caspase inhibitors-2 and 3, and MAPK inhibitor U0126 all failed to prevent vasospasm. MAPK inhibitor PD98059 partially prevented vasospasm. Our data demonstrated a metabolic alteration of glucose, glutamate, lactate and pyruvate in CSF during cerebral vasospasm. This metabolic change in consistent with the time course of cerebral vasospasm. This study suggests that brain energy metabolites and excitative amino acids are altered during cerebral vasospasm. PMID- 11210440 TI - The effects of the pre-treatment of intravenous nimodipine on Na(+)-K+/Mg+2 ATPase, Ca+2/Mg+2 ATPase, lipid peroxidation and early ultrastructural findings following middle cerebral artery occlusion in the rat. AB - Excessive calcium influx has been implicated in the pathophysiology of ischemic cerebral damage. The effects of nimodipine, a calcium antagonist, on the Na(+) K+/MG+2 ATPase activity, Ca+2/Mg+2 ATPase, lipid peroxidation, and early ultrastructural findings were examined at the acute stage of ischemia in the rat brain. Ischemia was produced by permanent unilateral occlusion of the middle cerebral artery. In Group I, the rats which had no ischemia and not received medication were used for determining Na(+)-K+/Mg+2 ATPase, Ca+2/Mg+2 ATPase, the extent of lipid peroxidation by measuring the malondialdehyde content and normal ultrastructural findings. In Group II, the rats which had only subtemporal craniectomy without occlusion and received saline solution were used for determining the effect of the surgical procedure on the biochemical indices and ultrastructural findings. In Group III, the rats received saline solution following the occlusion in the same amount of nimodipine and in the same duration as used in Group IV. In Group IV, nimodipine pre-treatment 15 min before occlusion (microgram kg-1 min-1 over a 10 min period) was applied i.v. Na(+) K+/Mg+2 ATPase and Ca+2/Mg+2 ATPase activities decreased significantly and promptly as early as 10 min and remained at a lower level than the contralateral hemisphere in the same group and at the normal level in Group I. Nimodipine pre treatment immediately attenuated the inactivation of Na(+)-K+/Mg+2 ATPase (p < 0.05) but there was no change on Ca+2/Mg+2 ATPase activity (p < 0.05). Malondialdehyde content increased significantly in Group III following ischemia as early as 30 min. Nimodipine pre-treatment decreased the malondialdehyde level in Group IV (p < 0.05). This study supports the possibility that nimodipine pre treatment effects the membrane stabilizing properties via inhibiting the lipid peroxidation and subsequently restoring some membrane bound and lipid dependent enzymes' activity such as Na(+)-K+/Mg+2 ATPase and the ultrastructural findings. PMID- 11210441 TI - Specific genetic markers of endurance performance and VO2max. AB - Specific genetic markers of endurance performance and VO2max. Exerc. Sport Sci. Rev., Vol. 29, No. 1, pp 15-19, 2001. Recent advances have revolutionized genetic studies of quantitative traits. Mitochondrial DNA and creatine kinase variations may influence VO2max. Other data strongly suggest that angiotensin-converting enzyme genotype affects VO2max and endurance performance capacity, but the mechanisms are unclear. A recent genome-wide scan study also has provided candidate loci requiring further study. PMID- 11210442 TI - Surface electromyography for noninvasive characterization of muscle. AB - Surface electromyography for noninvasive characterization of muscle. Exerc. Sport Sci. Rev., Vol. 29, No. 1, pp 20-25, 2001. Linear electrode arrays are used for noninvasive muscle characterization to study individual motor unit properties and the myoelectric manifestations of muscle fatigue during sustained contractions. The location of an electrode pair with respect to the innervation zone(s), the deterministic rather than stochastic nature of the signal, and the possibility of noninvasive fiber typing are discussed. PMID- 11210443 TI - Low back stability: from formal description to issues for performance and rehabilitation. AB - Low back stability: from formal description to issues for performance and rehabilitation. Exerc. Sport Sci. Rev. Vol. 29, No. 1, pp. 26-31, 2001. The concept of stability, together with notions of design and the application of stabilization exercise, is briefly synthesized. The objective is to challenge muscle systems to achieve sufficient functional stability but in a way that spares the spine of excessive exacerbating load. PMID- 11210444 TI - Electron paramagnetic resonance: a high-resolution tool for muscle physiology. AB - Electron paramagnetic resonance: a high-resolution tool for muscle physiology. Exerc. Sport Sci. Rev., Vol. 29, No. 1, pp 3-6, 2001. Skeletal muscle function can be altered by changes in protein structure and motion. Electron paramagnetic resonance (EPR) paired with site-directed spin labeling has been used to study the relationships between (a) muscle force and myosin structure and (b) muscle relaxation and Ca-ATPase motion and structure. PMID- 11210445 TI - Objective measurement of physical activity in youth: current issues, future directions. AB - Objective measurement of physical activity in youth: current issues, future directions. Exerc. Sport Sci. Rev., Vol. 29, No. 1, pp 32-36, 2001. Second generation activity monitors have revolutionized the way in which we measure youth physical activity. Use of the monitors avoids the problems associated with self-report methods and allows for the estimation of physical activity patterns over time. This article examines important methodological issues related to the use of activity monitors in children and adolescents. PMID- 11210446 TI - Impact forces and muscle tuning: a new paradigm. AB - Impact forces and muscle tuning: a new paradigm. Exerc. Sport Sci. Rev., Vol. 29, No. 1, pp 37-41, 2001. We propose that repetitive impact forces during physical activities are not important from an injury perspective but are the reason for changes in myoelectric activity (muscle tuning) to minimize soft tissue vibrations. Changes in myoelectric activity (intensity, frequency, timing), comfort, and performance provide supporting evidence for this new paradigm. PMID- 11210447 TI - Regulation of lipid mobilization and oxidation during exercise in obesity. AB - Regulation of lipid mobilization and oxidation during exercise in obesity. Exerc. Sport Sci. Rev. Vol. 29, No. 1, pp 42-46, 2001. Obesity is associated with metabolic disorders that may be related to alterations in lipid mobilization and oxidation. Although exercise is essential for successful weight management, the regulation of fatty acid metabolism during exercise in obesity is unclear. This review discusses factors that regulate fat metabolism during exercise and the effects of endurance training on these responses. PMID- 11210448 TI - Animal genetic models for complex traits of physical capacity. AB - Animal genetic models for complex traits of physical capacity. Exerc. Sport Sci. Rev., Vol. 29, No. 1, pp 7-14, 2001. Understanding the genetic basis for variance in complex physical traits such as aerobic capacity has become an attainable goal. A starting point is the development or identification of animal genetic models that contrast the low and high values for the trait of interest. Genes that cause natural trait variation can ultimately be determined from animal models via genetic linkage. PMID- 11210449 TI - Community as client: environmental issues in the real world. A SimCity computer simulation. AB - The ability to think critically has become a crucial part of professional practice and education. SimCity, a popular computer simulation game, provides an opportunity to practice community assessment and interventions using a systems approach. SimCity is an interactive computer simulation game in which the player takes an active part in community planning. SimCity is supported on either a Windows 95/98 or a Macintosh platform and is available on CD-ROM at retail stores or at www.simcity.com. Students complete a tutorial and then apply a selected scenario in SimCity. Scenarios consist of hypothetical communities that have varying types and degrees of environmental problems, e.g., traffic, crime, nuclear meltdown, flooding, fire, and earthquakes. In problem solving with the simulated scenarios, students (a) identify systems and subsystems within the community that are critical factors impacting the environmental health of the community, (b) create changes in the systems and subsystems in an effort to solve the environmental health problem, and (c) evaluate the effectiveness of interventions based on the game score, demographic and fiscal data, and amount of community support. Because the consequences of planned intervention are part of the simulation, nursing students are able to develop critical-thinking skills. The simulation provides essential content in community planning in an interesting and interactive format. PMID- 11210450 TI - Developing clinical practice environments supporting the knowledge work of nurses. AB - Registered nurses represent the largest group of healthcare knowledge workers. They accomplish their knowledge work by engaging in the roles of data gatherer, information user, knowledge user, and knowledge builder. To successfully implement these roles, nurses rely on healthcare settings to provide supportive clinical practice environments that recognize their information and knowledge management needs. The authors describe the various knowledge-worker roles, delineate computerized mechanisms that can support these roles, and examine the ability of current healthcare settings to provide an environment conducive to successful knowledge-worker role performance. The article concludes with specific recommendations for development of clinical practice environments supportive of nurses' knowledge work. PMID- 11210451 TI - Computer-mediated support group use among parents of children with cancer--an exploratory study. AB - This study describes aspects of computer group use as a vehicle for self-help by parents of children with cancer. Using an electronic mail system, data were gathered from 73 parents who had participated in online support groups. Most participants were Caucasian, well educated, and reported annual incomes of more than $50,000. The perceived benefits of the computer group involvement were getting information, sharing experiences, receiving general support, venting feelings, gaining accessibility, and using writing. The disadvantages included "noise," negative emotions, large volume of mail, and lack of physical contact and proximity. The findings indicate that computer group use is more common in parents with relatively high socioeconomic status. There are certain advantages and disadvantages of computer group use that need to be recognized and addressed by health professionals and users. PMID- 11210452 TI - Nurse practitioner use of computer technologies in practice. AB - A study was undertaken to determine computer use by nurse practitioners in public clinics, private practice, health maintenance organizations, and other settings in the greater San Francisco Bay Area. The descriptive research used a survey design. Subjects were 200 nurse practitioners. The survey instrument was developed by the researcher. Of the 104 respondents, 86 (83%) used computers at work. "Obtaining client records from other agencies or departments" was rated the most useful computer application for improving client care. "Internet searches" was rated the next most useful computer application; "entering client record information" was rated the third most useful. Use of computer applications varied by practice setting. Only 7 (25%) nurse practitioners in private practice accessed client records from other agencies, as did 17 (57%) in public clinics, and nearly all, 29 (94%), in HMOs. The research demonstrated that nurse practitioners underused computer applications that would improve client care in their practice. PMID- 11210453 TI - [Reactive invagination of the neuroepithelium in anlages of the human neocortex, tectum of the midbrain, and the retina at various stages of development]. AB - Intensity of invagination of neuroepithelium of neocortex of human embryonal anlages of neocortex, tectum of the midbrain and retina was studied as a response to mechanic damage of ventricular zone induced in the course of preparation of the anlages to explanation. It was shown that no invagination formed in 24 hrs of the explantation. In neocortical anlage intensity of invagination was meximal in 6.5 wks embryo. In tectum invagination intensity of th explants lowered gradually from wk 5 to wk 7. PMID- 11210454 TI - [Characteristics of the functional organization of neuronal groups in functionally diverse zones of the human cerebral cortex from birth to 20 years of age]. AB - Using computer analysis of histological specimens of motor and posterior associative cortex of the man aged from birth up to 20 yrs age and individual peculiarities of focal groups sublayer III3 of areas 4p, 6op and 37ac, periods of intensive and slow growth of the area of profile fields (PF) of cell groups and total area (TA) of neurons in the group were established. It was shown that greater changes of cell groups PF area and neuron TA occurred in the area 4p during first 3 yrs, while in areas 6op and 37ac from birth up to 7 yrs and 8-9 yrs appropriately. Specific features of the group development in functionally different areas of human brain cortex was demonstrated. PMID- 11210455 TI - [Layer-to-layer distribution of neurons and macroglial cells in various zones of the cat auditory cortex (quantitative study)]. AB - Quantitative analysis of layer-to-layer distribution of neurons and macrogliocytes in zones AI, AII, Ep and Ins of cat brain was performed in specimens stained after Einarson. Zones of auditory cortex were shown not to differ in density of neuron distribution. In every zone the neuron number in layers II, III and VI was significantly higher than in layers IV and V and in layers III and IV of zones AI and AII the number of neurons with macroglial satellites was almost twices higher than in the same layers of zones Ep and Ins. Fraction of neurons with different number of satellites shows significant diversities as well. In layers IV, V and VI of zones AI and AII both total number of macrogliocytes and perineuronal satellites was significantly higher than in zones Ep and Ins. The number of perineuronal satellitocytes correlates both with neuron axonal length and the level of the cell functional activity. PMID- 11210456 TI - [Postischemic reorganization of dendritic architectonics of the hippocampal CA3 region in albino rats predisposed to seizures]. AB - Total short term ischemia of brain was induced experimentally in albino rats (10 min long clamp of heart vascular bundle). Using Golgi Silver nitrate impregnation geometry of pyramidal neurons dendritic tree was studied in sector of hippocampus in norm, postischemic period (d 1.30 and 90) healthy animals and those predisposed to cramps. Significant reduction of dendrite volume, total length, dendrite territory, parameters of dendrite arborization were shown on the background of stable numerical density of neurons in all animals who survived brain ischemia. The extent of reduction, volume and duration of changes of parameters of dendritic tree geometry was higher in animals predisposed to cramps than in high threshold animals without cramps. Possible mechanisms of postischemic neuron "epileptization" were discussed. PMID- 11210457 TI - [Ultrastructure of the trigeminal principal sensory nucleus in the norm and during pain threshold stimulation]. AB - Ultrastructural organization of main sensory trigeminal nucleus neurons and synapses was studied in norm and in threshold pain irritation of teeth pulp of the cat. The neurons were divided into small and large ones. The latter were identified according to ultrastructural organization of perikaryon and significant number of axo-somatic synapses, formed by presynaptic terminals of different size. These neurons react to threshold pain irritation. Changes were observed more often in axonic terminals than in the endings of specific pain afferent fibres. PMID- 11210459 TI - [Effect of embryonal nerve tissue transplantation on regeneration of dorsal roots of the rat spinal nerves]. AB - Using cobalt salts axonal ionophoresis posttraumatic regeneration of TXII dorsal roots nerve fibres in the zone of hemisection in conditions of 14 wks embryo spinal cord transplantation into the zone of trauma of spinal cord. Regro Invasion of dorsal roots nerve fibres into recipients posterior cords and Lissawers tract through the transitional zone "spinal cord--dorsal roots" was observed on posttransplantation d 14-120. It was show that afferent axons predominantly spread in substantia alba and substantia grisea caudal to the level of spinal cord transection with only individual fibres invading rostrad through the neuronal plate. In the transplants neurons were encountered up to d 120 of the observation although transplant neuropil was limited from recipient tissue brain by a glial and connective tissue scar. The influence of embryonal nervous tissue transplantation on intraspinal regeneration of dorsal roots afferents was discussed. PMID- 11210458 TI - [Sensory neurons and Schwann cells during pharmacologic stimulation of the nerve regeneration]. AB - Using the model of rat sciatic nerve transection and crush injury we studied influence of pyrimidine derivative xymedon on efficacy of regeneration of myelinated axons, number and phenotype of surviving sensory neurons (expressing GAP-43 and Bcl-2) and Schwann cells (S100, GAP-43, PCNA) on the 7th, 15th, 30th, 60th and 90th day after nerve injury. We found out that xymedon counteracts posttraumatic death of sensory neurons, stimulates regeneration of myelinated fibres and proliferation of Schwann cells. PMID- 11210460 TI - [Innervation of the humerus metaepiphysis in newborn and one year old children]. AB - Analysis of home and foreign literature on metaepiphyseal cartilage innervation and blood supply was presented, data on these organ diseases substantiate theoretical and clinical significance of the study was performed. Using macro microscopic preparation, histological study, automatic image analyzer branches of humerus proximal metaepiphysis were shown to originate from axillary and subscapulary nerves. Nerves and vessels penetrating in the cartilaginous canals form neurovascular complexes. Cartilaginous canals are located unevenly. Nervous structures were found in the canals and their characteristics was given. PMID- 11210461 TI - [Structure of lymphatic vessels in the human thighs]. AB - Peculiarities of construction of muscular coat of lymphatics of human legs (long, polylymphangion muscular bands, longitudinally oriented, localized in deep layers of lymphatics walls and forming branches into adjacent valves of lymphangions) are the base for grouped contractions of lymphangions in them. Predominance of these muscular fascicles in muscular coat of lymphatics of thigh provide combined action of group of adjacent lymphangions versus gravitation force in the walking man. PMID- 11210462 TI - [Morphological characteristics of the lymphoid tissues in the newborn children]. AB - Quantitative and qualitative analysis and statistical processing of thymus, trachea, duodenum ileum, coecum and appendix in newborns demonstrated that by the moment of birth peripheral immunogenesis organs were not equally formed due to peculiarities of their function in postnatal ontogenesis. Lymphoid nodules were absent in tracheal mucosa and adjacent lymph nodes showed loss of lymphoid noules aswell. However intensive formation of lymphoid structures took place in the walls of the gut, especially large intestine. The appendix, lymphoid tissue of which was not, in fact, developed at all, made an exception. PMID- 11210463 TI - [Inguinal lymph nodes of Rhesus macaque in hypokinesia and combined action of hypokinesia and hypergravity]. AB - Peculiarities of microanatomy and cytoarchitecture of inguinal lymph nodes were studied under the effect of hypokinezia and combined effect of hypokinezia and hypergravitation experimentally in mature macaque rhesus monkeys for the first time. The data obtained indicate that on the background of intensive impairing effect of hypokinezia combined action was not only neutralized but the effect of hypokinezia also intensifies immunological action of lymph nodes of monkeys. This was supported by morphological signs and changes in correlation between lymphoid cells: number growth of lymphoid nodules with widened germinal centres and high fraction of mitotically dividing cells, the presence of dense thymus dependent (paracortical) zone and more dense medullar bands, filled basically with small lymphocytes and lowered level of destructive processes in all structural components of lymph nodes. PMID- 11210464 TI - [Structural characteristics of the adrenal cortex from rats with stress-induced hereditary arterial hypertension in the late postnatal ontogenesis]. AB - The comparative investigation of the adrenal cortex in hypertensive (INHERITED STRESS-INDUCED ARTERIAL HYPERTENSION--ISIAH) and normotensive strain (Wistar) 12 months age rats was performed. The structural signs such as the lowering of the mitochondria volume involved in steroid synthesis in showed more notable age related reduction of steroidogenesis in the adrenal glomerular and fascicular zones and in the ISIAH rats. The lowering of the cell steroidogenesis was compensated by the adrenal glomerular and fascicular zones and hypertrophy as a result the adrenocorticocytes hyperplasia. At the same time the more considerable sclerotic changes of the adrenal cortex periendothelial space were demonstrated in the ISIAH rats. The results obtained give evidence that reducing potential of compensatory possibilities of the adrenal cortex of the ISIAH rats in the late postnatal ontogenesis period cause high probability of adaptative-compensatory mechanisms failure and pathological process aggravation in these animals. PMID- 11210465 TI - [Effect of xenobiotics on alveolar macrophages]. AB - Under the action of hexachlorcyclogexan in concentration not exceeding the pesticides residues in food staffs the prominent adaptive mechanisms stress of gematoalveolar barier is seen. However, the adaptation has the extensive character and is caused by increase of alveolar monocytes in broncho-alveolar lavage. The phagocytosis functional reservers exceed the control values, but phagocytes activity and phagocytory index remain decreased and reach norms just after the xenobiotic abolition. PMID- 11210466 TI - [Effect of the long-term enteral administration of sorbents on the structural organization of microvillus mucosa in the small intestine]. AB - Long term use of diatomite and ceolite, SUMS-1 sorbents in ration exerts irreversible effect on structural organization of microarea of mucosa small intestinal villus causing changes that indicate activation of absorption, barrier function of interstitium, stimulation of the ansendothelial fluid perfusion into blood and lymphatic capillaries. SUMS-1 and ceolite showed the highest stimulative effect. PMID- 11210467 TI - [Applied (topographic) anatomy in Russia at the verge of XX-XXI centuries]. PMID- 11210468 TI - [Afferent and efferent pathways between the heart and hypothalamus]. PMID- 11210469 TI - [Experience in the course project preparation at the Department of Human Physiology]. PMID- 11210470 TI - [Enzyme activity in the cerebrospinal fluid in patients with brain gliomas]. AB - The spinal fluid activities of aspartate aminotransferase (AAT), alkaline phosphatase (AP), and gamma-gluthamyl transferase were studied in 32 patients with cerebral gliomas to clarify the diagnostic role of these enzymes. There were different changes in their activities in groups of patients with low-differential and differential gliomas. Its was ascertained that higher AAT activity was due to the fact that blood had entered spinal fluid; increased AP activity may be regarded to be an indicator of higher permeability of the blood-brain barrier. PMID- 11210471 TI - [Pathomorphological characteristics of cerebral arterioles and capillaries in surgical epileptic patients with generalized seizures]. AB - Clinical and morphological analyses of brain biopsy specimens from epileptic patients undergone surgery have indicated that the brain vascular system in epilepsy has the most vulnerable site, namely: pre-capillary arterioles and capillaries. At the same time, the paper describes some dissimilarities of qualitative and quantitative characteristics of the above vessels from their changes in hypertensive angiopathy. There was a relationship of arteriolar changes to the duration and severity of epilepsy. The use of silver-impregnated serial brain sections revealed 5 types of cerebral capillary morphological changes that could be arranged in successive stages of transformation (neocapillarogenesis). There was an association of the activation of neocappilarogenesis with the duration and severity of epilepsy. It forms an impression that the life of a capillary is shorter due to its accelerated morphofunctional evolution particularly in patients with advanced epilepsy. This is accompanied by the rates of neocapillarogenesis that is regarded as a compensatory and adaptive response of the brain capillary system. PMID- 11210472 TI - [Circulating immune complexes in acute concussion of the brain]. AB - The aim of the study was to study the count of circulating immune complexes (CIC) in the blood of children with acute concussion of the brain. The fact that CIC at high concentrations that can penetrate into the brain through the blood-brain barrier and cause complications as vasculitis, microangiopathy, proliferative processes in the meninges, enlarged ventricles of the brain, and atrophy of its tissue was borne in mind. The studies revealed a significant progressive CIC increase within 3 weeks. For correction of blood CIC levels, laser exposure was applied to the carotid and vertebral arteries and acupuncture points. For comparison, thymaline in age-specific doses was used. Laser radiation showed a significant fall of CIC at days 19-21, particular when applied to the acupuncture points. Thymaline did not affect blood CIC levels. Laser application to the acupuncture points in children with acute brain concussion should reduce the incidence of complications of brain injury disease. PMID- 11210474 TI - [Apoptosis: mechanism, regulation, and importance for neurooncology]. PMID- 11210473 TI - [Psychosurgical approach in neurosurgery]. PMID- 11210475 TI - [Intravascular blood aspiration in large and giant parawedge aneurysm surgery]. AB - The efficiency of a procedure of intravascular blood aspiration (IVBA) in patients with large and giant parawedge aneurysms of the internal carotid. The study was based on the analysis of clinical data and outcomes of surgical treatment in 20 patients with the aneurysms. The paper presents different procedures for IVBA, a complex of methods for preoperative examination of patients and intraoperative prediction of possible ischemic complications and defines indications for the IVBA procedure. Complete and partial aneurysm exclusion was achieved in 15 (75%) and 2 (10%) patients; the neck and walls of aneurysm were strengthened with surgical gauze in 2 (10%) patients. Incompetent clipping was observed in one case. There was recovery in 17 (85%), improvement in 2 (10%), 1 (5%) patients. No deaths occurred. The IVBA procedure for aneurysm is indicated for large and giant thin-walled non-thrombotic aneurysms of the parawedge carotid segment. It permit effective proximal monitoring of carotid blood flow and creates favourable conditions for preparing and excluding aneurysm, and, if necessary, forming a carotid lumen. Intraoperative monitoring of brain function is highly important and obligatory for early prediction and prevention of ischemic complications. Under intraoperative monitoring of brain function, fractional IVBA makes it effective even if collateral circulation is inadequate. PMID- 11210476 TI - [Neurosurgical clinic on Solianka str]. PMID- 11210477 TI - [Endoscopic interventions in tumors of the pineal area, posterior regions of the III ventricle, and the posterior cranial fossa]. AB - The study was undertaken to develop and introduce low-invasive differential endoneurosurgical correction of spinal fluid circulatory disorders in tumors of the pineal area, posterior portions of the third ventricle and the posteranial fossa. The authors present their experience in surgically treating 12 patients by using endoscopy. Surgical techniques, endoscopic semiotics of tumors of the above site, metastases along the liquor pathways are described. The outcomes of this treatment are analyzed. An algorithm of surgical treatment is proposed. Certain advantages of endoscopic interventions over conventional treatments in the treatment of tumor-induced occlusive hydrocephalus justify their inclusion into a comprehensive examination and treatment of patients of this study group. PMID- 11210478 TI - Handheld computers making the rounds with physicians. Devices put medical know how--literally--in the palm of your hand. PMID- 11210479 TI - Physicians toe regulatory line. Practices develop "voluntary" compliance plans. PMID- 11210480 TI - Can I depend on coverage in my absence? PMID- 11210481 TI - Impact of directly observed therapy on tuberculosis in Memphis and Shelby County. PMID- 11210483 TI - The phthisis still with us. Tuberculosis: the white plague is not yet a ghost of the past. PMID- 11210482 TI - A rare cause of dyspnea and fibrocystic pulmonary disease. AB - Tracheobronchomegaly (TBM) is a disorder of the major airways characterized by an enlargement of the trachea and main stem bronchi. It is thought to result from a congenital connective tissue defect that results in the trachea and main bronchi becoming flaccid. Although TBM is considered rare, it may be more common than is generally recognized, and may be a seldom-diagnosed cause of chronic lung disease. PMID- 11210484 TI - [Prevalence of goiter and iodine deficiency in Saxony is less than previously assumed. A study 6 years after discontinuation of general iodization of table salt]. AB - BACKGROUND: Germany is a known area of goitre endemicity. In East Germany (former German Democratic Republic), iodization of pre-packed table salt was introduced in 1985 and was only abolished after German reunification in 1990. Public awareness campaigns have concentrated on the use of iodized salt in the products of bakers and butchers as well as canned and frozen food since. Reports in the literature give figures of goitre prevalence (13 to 69%) inconsistent with each other and with our own clinical experience (about 30%). METHOD: We undertook a prospective cross-sectional study with a non randomly selected population (craftsmen and -women) covering Saxony in 1996, 1,129 and 1,594 adults were examined in 1996 and 1997, respectively, using a questionnaire, ultrasound, and measurement of urinary iodine excretion (1996 only). RESULTS: We found the following (mean) results in men/women in 1996: thyroid volume 23.0 +/- 1.3/17.1 +/- 1.5 ml, prevalence of goitre 32.1/31.3%, prevalence of thyroid nodules 21.1/23.0%, urinary iodine excretion (per creatinine) 86.4 +/- 1.3/104 +/- 24.1 nmol/mmol (97.1 +/- 1.4/117 +/- 27.1 micrograms/g). In 1997 the results were as follows: thyroid volume 20.9 +/- 1.2/15.7 +/- 2.1 ml, prevalence of goitre 25.6/23.6%, prevalence of thyroid nodules 16.4/19.8%. CONCLUSION: Whilst goitre and iodine deficiency are still endemic in Saxony, both have been improving despite the abolition of general table salt iodization. PMID- 11210485 TI - [Pathogenesis of bronchial asthma--unveiling new therapeutic prospects]. AB - BACKGROUND: Bronchial asthma is a chronic inflammatory disease of the lower respiratory tract. It is characterized by nonspecific bronchial hyperresponsiveness, which may lead to variable, reversible airflow obstruction in affected patients. Despite therapeutic improvements, the worldwide prevalence and morbidity of asthma have risen during the past decades. An improved understanding of underlying pathological features and mechanisms of asthmatic inflammation is essential to achieve an enhanced asthma symptom control and may lead to prevention in the future. RESULTS: Besides the impact of genetic and environmental factors, scientific interest has especially been focused on the molecular and cellular biology of the asthmatic response. Mucosal inflammation in asthmatics is mainly orchestrated by T cells and derived cytokines. Immunoglobulin E and mast cells play a pivotal role in the initiation and pathogenesis of the early asthmatic reaction, while recruitment and activation of eosinophils seem to be crucial for the persistent asthma phenotype with chronic airflow obstruction. Additionally, smooth muscle cells, parasympathetic nerve fibers, bronchial epithelial cells and a vast amount of mediators may either promote or inhibit the inflammatory pathology of bronchial asthma. CONCLUSION: The recent insights from molecular biology have found their correlate in actual therapeutic guidelines, and have further led to the development of new innovative asthma drugs such as monoclonal antibodies against IgE or IL-5. Hopefully, future progress in revealing pathogenetic mechanisms of asthma may lead to further therapeutic improvement and eventually reverse the trend of rising asthma morbidity in western societies. PMID- 11210486 TI - [Preoperative risk assessment and perioperative management of HIV-infected patients]. AB - PROBLEM: Due to their impaired immune function, unusual multimorbidity, and extensive concomitant medication HIV-infected patients impose special and specific demands on those who deal with their perioperative care. PREOPERATIVE ASSESSMENT: Beside standardized diagnostic and therapeutic preparations the preoperative knowledge, quantification, and treatment of HIV-associated opportunistic disorders and chronic organ damage are of particular importance. This requires an extended problem-orientated work-up. Furthermore, antiretroviral medication may interact with perioperatively administered pharmaceutics and lead to hardly foreseeable synergistic and antagonistic adverse effects. In contrast, "drug holidays" favor the development of HIV drug resistance. OPERATIVE MANAGEMENT: Anesthetic and surgical procedures basically depend on the underlying indication and consequently follow common principles. Laparoscopic techniques do not have any specific advantage in HIV-infected subjects. PERIOPERATIVE MORBIDITY: During their postoperative course, HIV-infected patients have to be more often admitted to intensive care unit and kept on artificial respiration unplannedly. Perioperative morbidity of HIV-infected patients increases with the stage of their disease. It is, however, not significantly elevated compared to that of HIV-negative subjects in similar preoperative health condition. PMID- 11210487 TI - [Diagnosis and therapy of Gaucher disease. Current recommendations of German therapy centers in the year 2000]. AB - BACKGROUND: Gaucher's disease is the autosomally recessively inherited deficiency of the lysosomal enzyme glucocerebrosidase. Increasing storage of glucocerebrosides leads to a multisystem disease, the prevalence of which is about 1:40,000 in central Europe and up to 1:2,000 in some other countries (e.g. Israel). The acute and chronic neuronopathic forms of the disease (formerly defined as Gaucher types 2 and 3) account for only 5 to 10% of all Gaucher patients in Central Europe and Germany and are thus less frequent than the non neuronopathic disease (formerly defined as Gaucher type 1). Gaucher's disease is usually associated with spleno- and hepatomegaly, fatigue, skeletal complications, and several corresponding hematological and laboratory abnormalities. In 5 to 10% of the patients there are also central nervous symptoms such as myoclonic seizures, oculomotoric apraxia and a slight mental retardation. METHODS: Four specialized centers care for more than 2/3 of all German Gaucher patients today. These centers present their consensus recommendations for state-of-the-art diagnosis and treatment of Gaucher's disease. RESULTS: Recent epidemiological data indicate that only 10 to 20% of all Gaucher patients are correctly diagnosed (and treated) in Germany. The diagnosis today can be done in all patients by noninvasive methods, i.e. determination of the glucocerebrosidase activity in peripheral leukocytes and of the genetic defect. The current enzyme replacement therapy with glucocerebrosidase has proven effective to improve and often normalize hematological abnormalities, hepatosplenomegaly, skeletal complications and quality of life, provided that the therapy is started early and is given at adequate dosages. CONCLUSION: In view of the availability of an effective therapy, efforts should be made to increase the awareness of Gaucher's disease in differential diagnosis, to help to diagnose the disease with noninvasive techniques at early stages, and to provide practical guidelines for adequate treatment. PMID- 11210488 TI - [Rhabdomyolysis as a rare complication of theophylline poisoning]. AB - CASE REPORT: A case of a 73-year-old male with theophylline overdose complicated by rhabdomyolysis is reported. After uncontrolled self-medication with an unknown number of theophylline slow release 350 mg tablets and furosemide 40 mg tablets he was admitted with unspecific clinical signs like tachyarrhythmia, vomiting and restlessness. Maximum theophylline concentration was 66.5 mg/l, other abnormal laboratory findings included hypokalemia (2.8 mmol/l) and hyponatremia (123 mmol/l). The maximum creatinkinase level was measured after admission (32.29 mumol/s/l) accompanied by a serum myoglobin level of 3,789 micrograms/l. Immediate treatment with oral activated charcoal and continuous veno-venous hemodialysis (CVVH) was instituted, together with intravenous potassium and sodium chloride substitution, forced diuresis and continuous administration of intravenous metoprolol. The theophylline, creatinkinase and myoglobin levels decreased rapidly and there was no second rise in theophylline found. The patient survived without sequelae. CONCLUSION: Rhabdomyolysis is a rare complication of theophylline intoxication. In literature only a small number of cases are reported. Our results illustrate the necessity of a purposeful and fast management to successfully prevent renal failure or death. Some pathogenetic mechanisms of theophylline-induced rhabdomyolysis, epidemiologic data, risk factors and therapeutical principles will be demonstrated by a detailed literature survey. PMID- 11210489 TI - [An unusual etiology of erythrocytosis in a 23-year-old primiparous woman in the 22nd week of pregnancy]. AB - CASE REPORT: A 23-year-old pregnant woman presented with erythrocytosis and a spuriously elevated HbA1c. Family history revealed that her father has been treated with phlebotomies for the last 2 years because of erythrocytosis of unknown cause. An examination of the family members demonstrated that the patient and her father were carriers of the hemoglobin (Hb) variant Hb Andrew Minneapolis. DISCUSSION: Hb Andrew-Minneapolis belongs to a group of hemoglobin variants with a high oxygen affinity resulting in compensatory erythrocytosis. The carriers of such hemoglobin variants are usually clinically asymptomatic, exercise tolerance appears unimpaired and there is no higher incidence of cardiovascular diseases. There is no clear-cut evidence that a maternal hemoglobinopathy with high oxygen affinity is accompanied by negative consequences for the fetus or a higher abortion rate. CONCLUSION: Hemoglobinopathies with a high oxygen affinity are a rare but important differential diagnosis of polycythemia. Under these circumstances erythrocytosis has to be accepted as the primary mode of compensation and does not require treatment, as long as blood viscosity is kept within tolerable limits. An excessively elevated or lowered HbA1c without a history or symptoms of diabetes should lead to further investigations concerning the possibility of hemoglobinopathy. PMID- 11210490 TI - [Necrobiotic xanthogranuloma with skin and liver amyloidosis]. AB - BACKGROUND: Necrobiotic xanthogranuloma is a largely unknown disease. Both the frequency of this disease and the involvement of internal organs have clearly been underestimated until now. CASE REPORT: A patient was admitted because of ulcerating, xanthomatous, subcutaneous nodules, scleritis and conjunctivitis. Laboratory studies revealed an elevated erythrocyte sedimentation rate, a monoclonal IgG-lambda protein, a pancytopenia and later a hypocomplementemia. Furthermore, a hepatosplenomegaly and esophageal varices were found. A skin biopsy specimen showed a granulomatous infiltrate consisting of lymphocytes, histiocytes, plasma cells, foam cells as well as Touton and bizarre-appearing foreign-body giant cells and cholesterol clefts typical of necrobiotic xanthogranuloma besides a deposit of amyloid. A liver biopsy sample disclosed an amyloidosis of the parenchyma, too. Neither a therapy with chlorambucil and prednisolone nor with interferon alpha-2a resulted in improvement. CONCLUSION: Apart from treatment of skin lesions and ophthalmic manifestations further investigations are necessary because necrobiotic xanthogranuloma can be associated with malignancy and can involve internal viscera like lungs, heart and liver. PMID- 11210491 TI - [Cerebral calcinosis]. PMID- 11210493 TI - Discovery of hyperthermophilic microorganisms. PMID- 11210492 TI - [Impaired CD95-(Fas,APO-1-)apoptosis regulation is a progression factor in early MALT-type lymphoma genesis]. AB - BACKGROUND: MALT-type lymphomas are B cell tumors arising for so far unknown reasons on the background of chronic inflammation, e.g. Helicobacter pylori associated gastritis. T cells are supposed to have a positive impact on tumor growth, but fail in their control function. We therefore examined the interaction of T cells with malignant B cells in vitro and focused on T cell control which normally operates by CD95L/CD95-mediated apoptosis. PATIENTS AND METHODS: Malignant B cells were isolated from tumor tissues of 7 patients with low-grade MALT-type lymphoma and 4 patients with DLBL and cocultured in vitro with activated T cells. Normal memory B cells were used as control. We developed a T/B coculture assay for investigation of CD95L/CD95-mediated apoptosis. The influence of T cells on CD95 expression and survival of B cells was measured by FACS analysis. RESULTS: Activated T cells induced CD95 expression and thus enhanced sensitivity to CD95L-mediated apoptosis in normal memory B cells. However, malignant B cells from 3 out of 7 low-grade MALT-type lymphomas and all 4 gastric DLBLs resisted apoptosis, although the cells showed enhanced CD95 expression. CONCLUSION: Resistance to CD95L/CD95-mediated apoptosis allows malignant B cells from MALT-type lymphoma to escape T cell control and leads to prolonged survival. This phenomenon acts as a progression factor in early lymphomagenesis. PMID- 11210494 TI - Genome of Pyrococcus horikoshii OT3. PMID- 11210496 TI - Genome of Aquifex aeolicus. PMID- 11210495 TI - Genomic sequence of hyperthermophile, Pyrococcus furiosus: implications for physiology and enzymology. PMID- 11210497 TI - Genome of Thermotoga maritima MSB8. PMID- 11210498 TI - Classification of glycoside hydrolases and glycosyltransferases from hyperthermophiles. PMID- 11210499 TI - Beta-glycosidase from Sulfolobus solfataricus. PMID- 11210500 TI - Xylose isomerases from Thermotoga. PMID- 11210501 TI - Beta-mannanases from Thermotoga species. PMID- 11210502 TI - beta-Mannosidase from Thermotoga species. PMID- 11210503 TI - Alpha-D-galactosidases from Thermotoga species. PMID- 11210504 TI - Pyrococcus furiosus: large-scale cultivation and enzyme purification. PMID- 11210505 TI - alpha-Glucosidase from Pyrococcus furiosus. PMID- 11210506 TI - Amylolytic enzymes from hyperthermophiles. PMID- 11210507 TI - Cellulolytic enzymes from Thermotoga species. PMID- 11210508 TI - A phylogenetic perspective on hyperthermophilic microorganisms. PMID- 11210509 TI - Hyperthermophilic xylanases. PMID- 11210510 TI - Continuous cultivation of hyperthermophiles. PMID- 11210511 TI - Chitinase from Thermococcus kodakaraensis KOD1. PMID- 11210512 TI - Characterization of beta-glycosylhydrolases from Pyrococcus furiosus. PMID- 11210513 TI - Beta-Endoglucanase from Pyrococcus furiosus. PMID- 11210514 TI - alpha-Amylases and amylopullulanase from Pyrococcus furiosus. PMID- 11210515 TI - beta-Glucosidase CelB from Pyrococcus furiosus: production by Escherichia coli, purification, and in vitro evolution. PMID- 11210516 TI - Purification, characterization, and molecular modeling of pyrolysin and other extracellular thermostable serine proteases from hyperthermophilic microorganisms. PMID- 11210517 TI - Pyrrolidone carboxylpeptidase from Thermococcus litoralis. PMID- 11210518 TI - Genome of Methanocaldococcus (Methanococcus) jannaschii. PMID- 11210519 TI - Protease I from Pyrococcus furiosus. PMID- 11210520 TI - Archaeal proteasomes. PMID- 11210521 TI - Thiol protease from Thermococcus kodakaraensis KOD1. PMID- 11210522 TI - Proline dipeptidase from Pyrococcus furiosus. PMID- 11210523 TI - Prolyl oligopeptidase from Pyrococcus furiosus. PMID- 11210524 TI - Homomultimeric protease and putative bacteriocin homolog from Thermotoga maritima. PMID- 11210525 TI - Carboxylesterase from Sulfolobus solfataricus P1. PMID- 11210526 TI - Purification and characterization of yeast exocyst complex. PMID- 11210527 TI - Expression and properties of Rab4 and its effector rabaptin-4 in endocytic recycling. PMID- 11210528 TI - Purification of EEA1 from bovine brain cytosol using Rab5 affinity chromatography and activity assays. PMID- 11210530 TI - Fluorescence methods for monitoring interactions of Rab proteins with nucleotides, Rab escort protein, and geranylgeranyltransferase. PMID- 11210529 TI - Expression, purification, and characterization of Rab5 effector complex, rabaptin 5/rabex-5. PMID- 11210531 TI - Measurement of Rab5 protein kinase B/akt and regulation of ras-activated endocytosis. PMID- 11210532 TI - Expression, purification, and biochemical properties of rabkinesin-6 domains and their interactions with Rab6A. PMID- 11210533 TI - Expression and functional analyses of Rab8 and Rab11a in exocytic transport from trans-Golgi network. PMID- 11210534 TI - Expression and properties of Rab7 in endosome function. PMID- 11210535 TI - Expression, purification, and properties of Rab8 function in actin cortical skeleton organization and polarized transport. PMID- 11210536 TI - Properties of Rab13 interaction with rod cGMP phosphodiesterase delta subunit. PMID- 11210537 TI - Subcellular localization of Rab17 by cryo-immunogold electron microscopy in epithelial cells grown on polycarbonate filters. PMID- 11210538 TI - Expression and properties of Rab25 in polarized Madin-Darby canine kidney cells. PMID- 11210539 TI - Purification of TRAPP from Saccharomyces cerevisiae and identification of its mammalian counterpart. PMID- 11210540 TI - Structural and functional organization of ADP-ribosylation factor (ARF) proteins. PMID- 11210541 TI - Expression and properties of ADP-ribosylation factor (ARF6) in endocytic pathways. PMID- 11210542 TI - Expression and analysis of ARNO and ARNO mutants and their effects on ADP ribosylation factor (ARF)-mediated actin cytoskeletal rearrangements. PMID- 11210543 TI - Expression, purification, and measurements of activity of ARNO1, a guanine nucleotide exchange factor for ADP-ribosylation factor 1 (ARF1). PMID- 11210544 TI - Expression, purification, and biochemical properties of EFA6, a Sec7 domain containing guanine exchange factor for ADP-ribosylation factor 6 (ARF6). PMID- 11210545 TI - Isolation and properties of GRP1, an ADP-ribosylation factor (ARF)-guanine nucleotide exchange protein regulated by phosphatidylinositol 3,4,5 trisphosphate. PMID- 11210546 TI - Functional analysis of ADP-ribosylation factor (ARF) guanine nucleotide exchange factors Gea1p and Gea2p in yeast. PMID- 11210547 TI - Structural basis for Rab function: an overview. PMID- 11210548 TI - Isolation, cloning, and characterization of brefeldin A-inhibited guanine nucleotide-exchange protein for ADP-ribosylation factor. PMID- 11210550 TI - Prenylation of Rab proteins in vitro by geranylgeranyltransferases. PMID- 11210549 TI - Expression, purification, and properties of ADP-ribosylation factor (ARF) GTPase activating protein-1. PMID- 11210551 TI - Expression, analysis, and properties of yeast ADP-ribosylation factor (ARF) GTPase activating proteins (GAPs) Gcs1 and Glo3. PMID- 11210552 TI - Purification and properties of ARD1, an ADP-ribosylation factor (ARF)-related protein with GTPase-activating domain. PMID- 11210553 TI - Purification and characterization of GIT family of ADP-ribosylation factor (ARF) GTPase-activating proteins. PMID- 11210554 TI - Assay and purification of phosphoinositide-dependent ADP-ribosylation factor (ARF) GTPase activating proteins. PMID- 11210555 TI - Biological properties and measurement of phospholipase D activation by ADP ribosylation factor (ARF). PMID- 11210556 TI - Use of aminoglycoside antibiotics and related compounds to study ADP-ribosylation factor (ARF)/coatomer function in Golgi traffic. PMID- 11210557 TI - Adaptor protein 1-dependent clathrin coat assembly on synthetic liposomes and Golgi membranes. PMID- 11210558 TI - Receptor-dependent formation of COPI-coated vesicles from chemically defined donor liposomes. PMID- 11210559 TI - Antibody and oligonucleotide probes to distinguish intracellular expression and localization patterns of Rab GDP-dissociation inhibitor isoforms. PMID- 11210560 TI - ADP-ribosylation factor (ARF) as regulator of spectrin assembly at Golgi complex. PMID- 11210561 TI - Purification, properties, and analysis of yARL3. PMID- 11210562 TI - Preparation and assay of recombinant ADP-ribosylation factor-like protein-1 (ARL1). PMID- 11210563 TI - Purification and properties of rat liver Sec23-Sec24 complex. AB - We have demonstrated a protocol for purifying functional Sec23-24 complex from rat liver cytosol. Because the rat liver Sec23-24 complex is highly susceptible to proteolysis, we have noted several modifications which have allowed us to overcome the problem of degradation. If care is taken to prevent proteolysis, this procedure typically yields 2 mg of functional complex. The Sec23-24 complex can then be used to study Sar1 GTP hydrolysis in the Sec23 GTPase activation assay. Additionally, Sec23-24 can reconstitute ER vesicle formation in the presence of Sar1 and Sec13-31, allowing for the identification of novel proteins or compounds that affect cargo export. PMID- 11210564 TI - Purification of functional Sec13p-Sec31p complex, a subunit of COPII coat. PMID- 11210565 TI - Expression, purification, and functional assays for self-association of dynamin 1. PMID- 11210566 TI - Analysis of phosphoinositide binding by pleckstrin homology domain from dynamin. PMID- 11210567 TI - Mapping dynamin interdomain interactions with yeast two-hybrid and glutathione S transferase pulldown experiments. PMID- 11210568 TI - Interactions of dynamin and amphiphysin with liposomes. PMID- 11210569 TI - Activation of dynamin GTPase activity by phosphoinositides and SH3 domain containing proteins. PMID- 11210570 TI - Expression and analysis of properties of septin CDCrel-1 in exocytosis. PMID- 11210571 TI - Expression, purification, and biochemical properties of Ypt/Rab GTPase-activating proteins of Gyp family. PMID- 11210572 TI - Purification and properties of Rab3 GDP/GTP exchange protein. PMID- 11210573 TI - Expression of wild-type and mutant green fluorescent protein-Rab1 for fluorescence microscopy analysis. PMID- 11210574 TI - Purification and properties of Rab3 GTPase-activating protein. PMID- 11210575 TI - Rabphilin-3: a target molecule for Rab3 small G proteins. PMID- 11210576 TI - Doc2 alpha as modulator of Ca(2+)-dependent exocytosis. PMID- 11210577 TI - Purification and properties of a GTPase-activating protein for yeast Rab GTPases. PMID- 11210579 TI - [Precocious and polymorphic factitious disorder]. AB - OBJECTIVE: Pathomimia is a mental disease more frequently diagnosed in women, characterised by a wide range of somatic or psychiatric symptoms, and a chronic course with severe complications. CASE REPORT: A 22-year-old woman was suffering from severe factitious disorders with thermopathomimia, dermopathomimia, self injuries with induced abscess, Lasthenie de Ferjol syndrome, and psychiatric factitious disorder. A very precocious age at onset and a previous history of 37 surgical operations were found. DISCUSSION: This case history is particularly relevant in showing the clinical multiplicity of factitious disorders. PMID- 11210578 TI - [Acute pyelonephritis. Randomized multicenter double-blind study comparing ciprofloxacin with combined ciprofloxacin and tobramycin]. AB - OBJECTIVES: To investigate the effects of an intravenous injection of tobramycin (T) in female patients with acute uncomplicated pyelonephritis treated with ciprofloxacin (CIP) (500 mg bid per os). METHODS: It was a randomized, multicenter, double-blind study conducted in six departments of emergency medicine. The main exclusion criteria were: previous history of urinary tract malformation of lithiasis, a recent urological procedure, pregnancy, diabetes mellitus, immunodepression, or severe sepsis. The primary criteria for evaluation were: the percentage and rate of clinical recovery, as well as bacteriological efficacy. RESULTS: 118 women were enrolled, 60 in the tobramycin group and 58 in the placebo group. E. coli was the most commonly isolated organism; all organisms were susceptible to ciprofloxacin and tobramycin. Two women in the CIP + T group and four women in the CIP + P group failed to respond clinically. The recovery rate was similar in the two groups (96 and 93% respectively). CONCLUSION: Administration of a dose of tobramycin did not demonstrate its clinical benefit in treatment of acute uncomplicated pyelonephritis treated by oral ciprofloxacin. PMID- 11210580 TI - [Cold parapharyngeal abscess in spondylodiscitis]. AB - BACKGROUND: The principle danger of pharyngeal abscess is the risk of rupture overflow into the upper respiratory track. Pyogenic abscesses are the most frequent and tuberculosis is rare. We report two cases of retro and parapharyngeal abscesses with tuberculous spondylodiscitis. CASE REPORTS: The first case occurred in a 54-year-old woman, the second in a 19-year-old man. Both had a laterocervical swelling associated with a oropharyneal bulge that progressed over several months. Computed tomography showed abscess formation and spinal disease in both cases. Drainage of the abscess led to the distological diagnosis of tuberculosis. Medical management was successful with resolution of the abscess and spinal lesions. DISCUSSION: Spinal tuberculosis should be suspected in patients with a parapharyngeal abscess without detectable portal that progresses slowly. A biopsy specimen is required for diagnosis. Magnetic resonance imaging can provide early evidence of spondylodiscities. Medical treatment is indicated. PMID- 11210581 TI - [Cyclosporiasis: an emerging intestinal protozoan infection]. PMID- 11210582 TI - [Double appendicitis: a rare clinical form in appendix duplication]. PMID- 11210583 TI - [Calcitonin-secreting neuroendocrine carcinoma of the pancreas with splenic invasion and paraneoplastic hypercalcemia]. PMID- 11210584 TI - ["Overlap" syndromes. Autoimmune hepatitis--primary biliary liver cirrhosis; autoimmune hepatitis--primary sclerosing cholangitis]. PMID- 11210585 TI - [40th ICAAC. Catheter-related septicemia]. AB - A GROWING PROBLEM: Insertion or use of intravascular material is increasingly associated with septicemia. Septicemia occurs in 1 out of 1000 patients undergoing a non-surgical invasive cardiac procedure. The frequency of septicemia, particularly due to Gram-negative bacteria, is increasingly frequent in stem-cell graft recipients. PREVENTION MEASURES: Educational programs, for both patients and health givers, emphasizing the importance of aseptic can reduce the incidence of Gram-negative bacteria catheter-related septicemias. PMID- 11210586 TI - [Teaching human anatomy by the American medical faculty. The example of Stanford]. PMID- 11210587 TI - [Ambulatory chemotherapy schedule for metastatic colorectal cancer]. PMID- 11210588 TI - [Iatrogenic risk of self-medication by the pregnant patient]. AB - REALITY OF SELF-MEDICATION IN PREGNANCY: Pregnant women use self-medication readily. Such behavior must not be overlooked by physicians and midwives during pregnancy. More epidemiology data would be useful. IATROGENIC RISKS: Drug toxicity, generally related to the advancement of somatic development of the embryo and fetus, can appear at variable stages during pregnancy. Moreover, the pharmacokinetic properties of drugs are different during pregnancy. These facts must be taken into account when assessing the risk of uncontrolled drug use by pregnant women. RECOMMENDATIONS FOR PREGNANT WOMEN: Obstetricians, midwives and primary care physicians caring for pregnant women should explain the risks of self-medication. The specific features of disease during pregnancy should be considered when giving relevant information. PMID- 11210589 TI - [Atherosclerosis--the role of nitric oxide]. AB - ATHEROSCLEROSIS: Currently regarded as a multifactorial disease, atherosclerosis involves several factor including: oxidized LDL, endothelial cells, macrophages, immune cells, vascular smooth muscle cells. The endothelium appears to play a key role through the production of vasomotor, antiaggregate and leukocyte antiadhesion molecules. NITRIC OXIDE: NO is one of the most important mediators of endothelial antiatherothrombotic functions. Loss of endothelial production, called "endothelial dysfunction", i.e. loss of endothelial vasorelaxing, antiaggregate and leukocyte antiadhesion properties, could lead to increased fatty streak formation and acute arterial events (thrombus formation, vascular spasm). ANIMAL EXPERIMENTS: Although animal models strongly suggest a major role for NO in the pathophysiology of atherosclerosis, human studies with nitrates have been disappointing to date. The local effect of NO is probably closely adapted to local conditions. Therefore, massive delivery of NO as is achieved with nitrates could not repair endothelial dysfunction. PMID- 11210590 TI - [An unusual stent of the renal artery]. PMID- 11210591 TI - [Predictive factors of virologic response to antiretroviral treatment with a protease inhibitor in HIV infection]. AB - OBJECTIVE: To investigate factors related to early virological response among a cohort of 224 patients who started a protease inhibitor (PI) for the first time. To determine which factors are associated with persistent response among patients with early response. PATIENTS AND METHODS: Early complete response was defined as an undetectable plasma viral load 2 to 3 months after treatment onset (< 400 copies/ml, Quantiplex HIV 2.0 Chiron diagnostics), incomplete response as at least 1 log reduction of viral load. In patients with an undetectable plasma viral load at 2 or 3 months, we also assessed the persistence of the response on the same regimen. Virology failure was defined by two consecutive viral load levels above the detection limit. RESULTS: In the total cohort, 66% of the patients had an early complete response, 11% a partial response and 23% no response. Complete virological response was significantly more frequent in naive (89%) than in pretreated (59%) patients (p < 0.001). Multivariate analysis of factors predictive of early response in pretreated patients (n = 169) showed that viral load (p = 0.001), the number of nucleoside analogs previously received (p = 0.06) and a full or partial treatment switch (p = 0.10) were associated with complete response. Analysis of later response in the 45 naive patients with prolonged follow-up showed that 22% had treatment failure after 3 to 16 months. None of the baseline variables (viral load, CD4+ cell count or nature of the PI) were associated with duration of response. The only factor associated with persistent response in pretreated patients was a low number of antiretroviral drugs previously received (log-rank test, p = 0.04). CONCLUSIONS: The absence of previous antiretroviral treatment as the main factor associated with an early complete virological response. In patients pretreated with nucleoside analogs who presented early virological success, the number of drugs previously received, often associated with full or partial switch of nucleoside analog, significantly influence the persistence of response to a given triple-drug regimen. PMID- 11210592 TI - Handle with care! Complex scoring systems in measuring health-related quality of life. Commentary on Wilson et al. "The SF-36 summary scales: problems and solutions". PMID- 11210593 TI - Ministers of Health, Environment, Traffic, Economy: you need to have lunch together! PMID- 11210594 TI - The SF-36 summary scales: problems and solutions. AB - To determine the accuracy of the SF-36 summary mental and physical health scales in reflecting their underlying subscales using the traditional method of scoring based on factor coefficients derived through principle components analysis and orthogonal rotation. A representative Australian population survey containing the SF-36 was used to obtain factor coefficients from principle components analysis and orthogonal rotation for scoring the physical component summary (PCS) and the mental component summary (MCS) of the SF-36 in the traditional way. In addition two other methods were used to produce coefficients. The first method used maximum likelihood extraction and oblique rotation. The second method fit a structural equation model to the data in a confirmatory factor analysis. The coefficients derived by each of the methods were applied to the data of a second representative population survey. This survey also provided data on physical and mental health status which allowed comparison of the summary scores and underlying subscales according to various health states. Neither of the scoring methods based on the exploratory factor analyses methods (orthogonal and oblique) produced summary scale scores, by age group, that adequately reflected the underlying subscales. When coefficients derived using structural equation modeling were fit to the data in a confirmatory factor analysis the MCS and PCS accurately reflected their underlying subscale scores. They also produced MCS and PCS scores for the various health states as would be expected from the underlying subscales. The traditional methods of scoring the SF-36 summary scales produce results that would not be expected from the underlying subscales. The problem was only corrected by fitting a structural equation model to the data in a confirmatory factor analysis. The results advise caution in the use of the SF-36 summary scales and suggests that alternative methods of developing factor coefficients need to be employed in studies using the SF-36 summary scales. PMID- 11210595 TI - Reproductive factors and incidence of breast cancer: an international ecological study. AB - Ecological studies can help in understanding the relation of reproductive history of breast cancer. We analyzed data from 9416 women, comprising the control groups of seven countries (Australia, People's Republic of China, Colombia, (former) German Democratic Republic, Israel, Philippines, and Thailand) from the WHO international, multi-center case-control study of female cancers. Positive correlations with country-specific breast cancer incidence were observed for (median) duration of reproductive life (r > or = 0.95, p < 0.005), age at menopause (r > or = 0.84, p < 0.025) and delay to first birth (r > or = 0.59, p < 0.22) (when People's Republic of China was omitted, r > or = 0.85, p < 0.07). The association of age at first birth with breast cancer incidence was weakly positive in the whole sample (age-adjusted r = 0.18, p = 0.73), but weakly negative in the age groups 15-29 and 30-39 years and weakly positive in the age groups 40-49 and 50-64 years. A strong inverse correlation was observed between age at menarche and breast cancer incidence (r < or = -0.84, p < 0.03). These international ecological correlations agree with the associations previously reported for single populations, between higher incidence of breast cancer and younger age at menarche, older age at menopause, longer duration of reproductive life, and (possibly) longer delay to first birth. In contrast, age at first birth is only weakly related to breast cancer incidence across populations, indicating that this variable represents different constructs when measured ecologically versus individually. PMID- 11210596 TI - [Reproducibility of a German scale for assessing the need for inpatient treatment in surgery]. AB - During the past years, the assessment of the appropriateness of hospital utilization has become increasingly important in the German health care system. Previous evaluations by regional review organizations in several states demonstrated the need for a standardized, reliable, and valid instrument to evaluate the appropriateness of inpatient care. Objective of the study is to test the reliability of a German adaptation of the "Appropriateness Evaluation Protocol" (AEP). Among all 2672 admissions from the department of surgery of a regional medical center during one calendar year, 54 patients were randomly selected to evaluate the inter-rater reliability and 51 patients to test intra rater reliability. Overall agreement, specific agreement and Kappa statistics were estimated for every hospital admissions and all consecutive hospital days. The German AEP showed an inter-rater agreement of 74% (62-86%) for hospital admissions (Kappa = 0.44) and 84% (79%-88%) for all hospital days (K = 0.55). Intra-rater reliability was 88% (79%-97%) for hospital admissions (K = 0.60) and 88% (85%-92%) for all hospital days (K = 0.70). The observed agreement is independent of length of hospital stay and proportion of appropriate days. A standardized instrument with known metric properties is essential for quality management in hospitals to prepare for an increasingly consolidating health care market in Germany. The German AEP is a reliable instrument, which will allow to identify inefficiencies in the management of surgical inpatients. PMID- 11210597 TI - [Vaccination against hepatitis B in school: factors influencing acceptance and evaluation of general vaccination coverage ]. AB - The second vaccination campaign against Hepatitis B in Lausanne concerned 1243 students of the seventh grade. This campaign was actively supported by personalized information given to each adolescent in the class room. The decisions were collected in the same way, and in necessary the nurse phoned the parents for further information. In comparison with the previous year, the coverage had grown from 63.5% to 78.5%, but varied in each class between 42% and 92%, whatever the class type. The factors which influence acceptance of the vaccination are coverage for the other vaccines, origin, and class, which has up to five times more effect than the other factors. Assessment of the vaccination coverage against Diphteria, Tetanus, Poliomyelitis, Pertussis, Measles and MMR is given in relation to the acceptance of the Hepatitis B vaccination and the class type. PMID- 11210598 TI - Body weight: the male and female perception. AB - The aim of the present study was to examine the relationship between actual body weight, characterization of one's weight, and satisfaction with it. 246 students of medicine in the third (clinical) stage of their studies at the University of Vienna responded to a questionnaire asking about their weight and attitudes regarding their personal body weight. The results indicate that many young women and men are either unable to characterize their weight (as normal, underweight, overweight, or obese) or guess incorrectly. The results point to the fact that a lot of women and men do not estimate their body weight in correspondence to the valid definition of the BMI. Women in particular seem to model themselves more on the current beauty ideal than men. Women seem to be more influenced by the current ideal of slenderness than their male counterparts. Women are more frequently dissatisfied with their weight, and see themselves as considerably heavier than they actually are. Because of this perception, women attempt to reduce weight more often than men. This type of dissatisfaction with one's body weight and excessive attention paid to body image, particularly weight, are considered as risk factors for the development of eating disorders. Not surprisingly, women are significantly more prone to these conditions than are men. PMID- 11210599 TI - Nicotine dependence among the population of a big Polish city. AB - Determinants of nicotine dependence types among current and former tobacco smokers were assessed in a random sample of Lodz inhabitants (25-64 years of age), part of the WHO CINDI project. Among current smokers there were 46.3% people with strong nicotine dependence, while in the group of ex-smokers the corresponding proportion was 10.8%. It has been found that sex, age and education did not affect the distribution of degree of the nicotine dependence. Prevalence of strong nicotine dependence among Polish regular smokers is high compared to other CINDI countries. PMID- 11210600 TI - [1000 thyroidectomies--personal experience and results]. AB - The authors made one thousand thyroidectomies in the course of five years. In the submitted paper they discuss indications, for surgery, the extent of the operations, the results of the histological findings. They describe the surgical procedure, required preoperative examinations and postoperative monitoring. They analyze different postoperative complications incl. their frequency in the discussed group. They emphasize a physiological surgical technique, verifications of the recurrent nerve, care of the parathyroid bodies and collaboration with endocrinologists. PMID- 11210601 TI - [Percutaneous lumbar sympathectomy--presentation of a new trans-diskal approach]. AB - The authors present the technique of chemical lumbar sympathectomy by an anatomically new medial transdiscal approach. On a group of 80 operations they analyze the indication criteria, complications and results of this method. They compare the percutaneous technique of severing of the sympathetic nerve with the classical surgical approach. In 41 patients where a modified transdiscal approach was used the authors did not encounter any serious complications. Using thin needles (minimum 23-G) they recommend this method as an alternative of the classical approach of Kappis. PMID- 11210602 TI - [Surgical treatment of spontaneous esophageal perforation--Boerhaave syndrome]. AB - Spontaneous rupture of the oesophagus (Boerhaave's syndrome) is a life threatening disease the successful treatment of which depends on early diagnosis and effective comprehensive treatment. The authors present an account on three patients who were successfully treated on account of spontaneous rupture of the oesophagus. PMID- 11210603 TI - [Early carcinoma of the esophagus]. AB - In 1991-1999 the authors performed at the First Surgical Clinic of the Faculty Hospital in Olomouc extirpation of the oesophagus on account of carcinoma in 133 patients. This number comprised only four patients with a tumour in its early stage. In all these instances an adenocarcinoma in Barrett's oesophagus was involved. The authors emphasize, that the generally poor prognosis of patients with carcinoma of the oesophagus is influenced to a considerably extent by its late diagnosis. The finding of carcinoma of the oesophagus in the early stage of the disease is usually possible only in case of malignization of Barrett's oesophagus. This is the reason why Barrett's oesophagus should be dealt with only in specialized departments concerned with diseases of the oesophagus in general. PMID- 11210604 TI - [Surgical treatment of pulmonary aspergilloma and its complications]. AB - The authors present an account of their experience with the surgical treatment of 44 patients with pulmonary aspergilloma who were treated at the Clinic of Pneumology and Thoracic Surgery of the Third Medical Faculty Charles University in Prague during 1957-1999. The diagnosis of the disease before surgery was made in 39 patients (88.6%), in five patients it was established only after histological examination following resection of the lung. The presence of an aspergilloma was observed most frequently in a TB cavern (n = 30) and in bronchiectatic cavities (n = 9) with the most frequent localization in the upper pulmonary lobes (n = 38) and prevalence on the right side (n = 23). The most frequent symptom of the disease was haemoptysis (n = 39). All patients with the established diagnosis were treated before surgery by antimycotics. Treatment was however not successful and therefore the patients were indicated for surgery. The preoperative diagnosis of aspergilloma was based on X-ray or CT examination, serological examination (positive in 92.8%) and cultivation of sputum (positive in 58.9%). The most frequent surgical operation was lobectomy (n = 20), segmentectomy (n = 9), atypical resection (n = 8), pneumonectomy (n = 3); cavernostomy was performed in four patients. The most serious postoperative complication was a bronchopleural fistula with subsequent empyema (n = 2). During the postoperative period three patients died from respiratory failure associated with bronchopneumonia (6.8%). The authors recommend, based on their own experience, an active approach in patients with pulmonary aspergilloma and consider surgery as the main therapeutic method. PMID- 11210605 TI - [Aortic reconstruction in neonates with hypoplastic left heart syndrome] . AB - The surgical technique and tactics of the Norwood operation in neonates with hypoplastic left heart syndrome represent a surgical challenge. The Norwood operation was performed from the midline sternotomy approach, in extracorporeal circulation and deep hypothermic circulatory arrest was used for reconstruction of the hypoplastic aorta. Operation consisted of reconstruction of the "neoaorta" and the aortic arch from the original hypoplastic ascendent aorta, pulmonary trunk and a patch cut from a pulmonary homograft or pericardium, excision of the atrial septum and an arterial shunt from a Goretex vascular graft 3.5 or 4 mm in diameter. In patients with well developed aortic arch it was possible to reconstruct the aorta using Damus-Kaye-Stansel operation without circulatory arrest. Out of 12 operated patients with this defect, two (16.7%) died during the early postoperative period, one patient died late. The postoperative course was often complicated. In 6 (50.0%) patients the second step of Norwood operation, the bidirectional cavopulmonary anastomosis, was performed without mortality. According to our experience, it was necessary to prepare patients adequately before the first surgery. Perfect reconstruction of the aorta and a well functioning shunt had the crucial significance. PMID- 11210607 TI - [Hemodynamic changes after sclerotherapy of esophageal varices in children]. AB - The authors present an account on favourable late results of sclerotization of oesophageal varices in children. After sclerotization not only an immediate effect can be observed such as arrest of haemorrhage but also long-term favourable effects are found in the venous circulation of the splanchnic area. PMID- 11210606 TI - [Evaluation of 26 esophagectomies from the aspects of complications and survival time]. AB - The authors analyze a group of 26 patients with oesophageal carcinoma operated in the course of five years with regard to postoperative complications and period of survival. In seven instances they used Ivor-Lewis operation, 17 times Orringer's operation, twice a palliative retrosternal bypass. Twenty one times they used the stomach for replacement of the oesophagus, five times the left hemicolon antiperoristaltically. The preoperative ASA classification was on average 3. The moribidity was 74%. Respiratory complications were most frequent--18x, paresis of the left vocal cord--7x, a fistula in the anastomosis--5x. The hospital mortality was 27%, its causes being cardiac failure, MOF, fistulae in the anastomosis. In seven instances the authors performed tracheostomy. Of 19 surviving patients 13 died after an average period of 10 months. Six patients survive on an average for 11 months. PMID- 11210608 TI - [Pleuro-dural communication]. AB - Traumatic pleuro-dural communication causing pneumocephalus needs rapid diagnostics and surgical treatment, so as to prevent the development of possible complications. PMID- 11210609 TI - [Surgical procedures on the external carotid artery]. AB - A clinical series of five patients operated on for symptomatic cerebral blood flow deterioration is discussed. They presented with either hemispheral symptoms (hemiparesis, amaurosis fugax) or signs of diffuse cerebral hypoxia. In the presence of unilateral or bilateral internal carotid artery (ICA) occlusion a critical stenosis of the external carotid artery (ECA) was confirmed either by duplex ultrasound or angiography. In all these cases ECA was reconstructed by means of common vascular surgical techniques. The use of intraluminal (i.l.) shunt was mandatory. There were neither early nor late deaths in this group. In one patient a transient stroke occurred three days following standard carotid endarterectomy performed after ECA surgery on the contralateral side. After the mean follow-up of 46 months all patients remain neurologically asymptomatic. In selected cases the ECA reconstruction offers an effective and beneficial tool for surgical management of critical cerebral perfusion impairment. PMID- 11210610 TI - [Laparoscopy in the diagnosis, classification and therapy of nonpalpable undescended testes]. AB - OBJECTIVE: The use of laparoscopy in children for the diagnosis, classification and treatment of non-palpable testes. High forms of undescended testes in an abdominal or high inguinal position are a diagnostic and therapeutic problem in paediatric surgery. METHOD: The authors evaluate retrospectively the laparoscopic approach used in 68 boys for the diagnosis, classification and treatment of 79 undescended testes. The mean age of the operated boys was 4.58 years. In 22 (27.9%) agenesis or atrophy of the testis was found (Type I). Thirty-two (40.5%) testes in an abdominal position (Type II) were mobilized laparoscopically, moved to the groin and the operation was completed by open orchidopexy. In 25 cases (31.6%) the laparoscopic method described by Fowler-Stephens was used treatment was completed by orchidopexy in the second stage (Type III and IV). RESULTS: No serious complications were recorded during or after operation. In two instances (2.5%) after the two-stage Fowler-Stephens operation atrophy of the testis developed. CONCLUSION: Miniinvasive laparoscopy is considered at present the standard method for the localization and treatment of non-palpable testes. PMID- 11210611 TI - [Injuries of the small intestine in polytrauma]. AB - The authors inform on the increasing number of penetrating abdominal injuries during the last five years, especially in the criminal injuries. Diagnostic methods in a stabilised patient are analysed, diagnostic and therapeutic laparoscopy is preferred to lavage of the abdominal cavity in indicated cases. Urgent surgical revision is recommended in patients in a critical state on account of quickly increasing compartment syndrome, although staged laparotomy is needed. The timing of surgical methods is emphasised in serious associated injuries. Conclusions are illustrated with surgical results. PMID- 11210612 TI - [Devastating injuries--new therapeutic approaches]. AB - Nowadays the number of devastating injuries is increasing, as a consequence of traffic accidents and criminal incidents, too. Patients are often admitted in a critical state, the mortality rate in these cases is very high (50% and more). To decrease this high mortality, new treatment approaches must be chosen incl. the method called damage control. Knowledge of leading foreign centres are evaluated together with our clinical experience. PMID- 11210614 TI - [Personal experience with mechanical intestinal anastomoses]. AB - The authors evaluated the results of operations of the large intestine and rectum on account of cancer, covering a 4-year period. In all instances a stapler or Valtrac were used. Dehiscence of the anastomosis was recorded in one instance. PMID- 11210613 TI - [Does a pelvic compartment exist? Personal experience]. AB - The authors analyze a group of 7 patients transferred to their hospital for instable fractures of the pelvic circle and lumbar spine. The pelvic compartment was manifested 24-48 hours after injury. Early diagnostics are based on the use of new imaging techniques, spiral CT examination is preferred, and angiography in stabilized patients. Early surgical intervention is aimed at evacuation of haematomas, revision of vessels, release of the ureters and temporary nephrostomy. PMID- 11210615 TI - [Distal crural bypass as a limb salvage procedure--case report]. AB - The authors present a case of a patient with a progredient moist gangrene of the right foot. In this patient, amputation of the lower limb was indicated because of an unfavourable angiographic finding, after unsuccessful conservative treatment. With regard to the fact, that the patient had undergone amputation of the other lower limb in the crus, revision of the posterior tibial artery was decided. Preoperative angiography did not confirm the previous unfavourable angiographic finding. After the implantation of a distal crural venous bypass (posterior tibial artery--supramalleolar part), healing of the extremity occurred in a relatively short time period. The authors agree with the opinion that distal crural and pedal bypasses cannot be always indicated on the basis of routinely performed angiography. Revision of crural arteries and possible preoperative angiography can change the situation and lead to the salvage of the limb. PMID- 11210616 TI - [Pathogenic properties of Corynebacterium diphtheriae]. AB - The main pathogenic properties of 73 C. diphtheriae strains (their adhesive, invasive and cytotoxic activity) were characterized in the cultures of cells HEp 2 and Vero. The quantitative determination of the toxigenicity of 381 strains in the indirect hemagglutination test was made, and the strains were distributed by the degree of their toxigenicity. The characteristics of C. diphtheriae obtained with the use of in vitro experimental models, coincided with the severity of clinical manifestations of the diphtheria in humans, which made it possible to regard the models used in this study as adequate. On the basis of the chosen criteria the characterized strains could be subdivided into highly, moderately and low virulent and the degree of their potential epidemic danger could be determined. PMID- 11210617 TI - [Pathogenicity factors of various vibrios and aeromonads]. AB - A review of literature on the pathogenicity factors of non-cholera vibrios and Aeromonas is presented. A detailed analysis of such pathogenicity factors as hemolysins, lecithinases, cytotoxins, adhesins, etc. is given. Information on some mechanisms of the pathogenetic action of these factors on warm-blooded animals is presented. The necessity of more extensive research on pathogenicity and persistence factors in opportunistic bacteria causing sapronotic infections is emphasized. PMID- 11210618 TI - [Helicobacter pylori in gastrointestinal diseases and in healthy individuals]. PMID- 11210619 TI - [Outbreak of acute enteric infections in a children boarding-school: iceberg phenomenon (part 1)]. PMID- 11210620 TI - [Cases of ornithosis in Moscow: most recent data]. PMID- 11210621 TI - [Outbreak of acute enteric infections in a children boarding school: iceberg phenomenon (part 2). Answers to questions and authors' commentary]. PMID- 11210622 TI - [Modern outlook at viral hepatitis A epidemiology in Moscow]. PMID- 11210623 TI - [Dibazol: a remedy for prophylaxis of acute respiratory infections among students of military colleges]. PMID- 11210624 TI - [Occurrence of Staphylococcus aureus enterotoxigenic strains isolated from pregnant women with pathology]. AB - 137 S. aureus strains, isolated from the larynx of pregnant women in cases of pathology, were studied for the formation of staphylococcal enterotoxins of types A and B (SEA and SEB) by the indirect hemagglutination test. The study revealed that SEA was produced by 35.0% and SEB, by 56.6% of the strains under study. The proportion of SEA and SEB producers among staphylococci isolated from mothers and children was, respectively, 18.4% and 20.0%, 89.41% and 67.5%. The number of enterotoxigenic staphylococci in the upper respiratory tract of newborn infants and mothers practically coincided with that in mothers. The occurrence of SEA- and SEB-producing enterotoxigenic strains in the medical personnel was 25.5% and 62.7% respectively. PMID- 11210625 TI - [Diagnostic value of a novel nutrient medium for isolation and cultivation of pathogens causing enteric yersiniosis and pseudotuberculosis]. AB - A new nutrient medium for isolation and cultivation of the causative agents of enteric yersiniosis and pseudotuberculosis was found to have advantages over Endo medium in its differentiating and inhibiting properties. This medium permitted the easy differentiation of Yersinia pseudotuberculosis from Y. enterocolitica, as well as from Escherichia coli, Shigella flexneri, Klebsiella pneumoniae, K. rhinoscleromatis, Hafnia, Enterobacter and Citrobacter by color; from Proteus inconstans by swarming. In addition, weakly swarming of P. vulgaris differed by their light bluish color and Pseudomonas aeruginosa, by the brilliance and size of colonies. Endo medium could be used only for differentiation of E. coli from lactose-negative Yersinia colonies, Klebsiella (by mucous growth) and, to a certain extent, all Proteus species (by swarming). The medium under test and the control medium inhibited the growth of Staphylococcus aureus. In contrast to Endo medium, the medium under test partially inhibited the growth of K. rhinoscleromatis and the swarming of P. inconstans. The new medium is now introduced into practice. PMID- 11210626 TI - [DNA, RNA, and protein biosynthesis in cells of Yersinia pseudotuberculosis at various cultivation temperatures]. AB - Y. pseudotuberculosis cells cultivated at temperatures of 37 degrees C and 8 degrees C were found to be capable of incorporating exogenic precursors into DNA, RNA and protein. The linear growth of thymidine incorporation occurred during 8 hours of cultivation at 37 degrees C, then the amount of the incorporated label decreased. At 8 degrees C the level of thymidine incorporation into DNA gradually increased for 80 hours and longer, but not reaching the level of incorporation observed at 37 degrees C. The incorporation of uridine into RNA of Y. pseudotuberculosis cells reached its maximum after 4 hours of cultivation at 37 degrees C, at a lower temperature of cultivation the incorporation of uridine into bacterial cells was almost linear, though slower, and lasted for 20 hours. The content of radioactive alanine in Y. pseudotuberculosis protein increased during 16 hours of cultivation at a high temperature, while at 8 degrees C the growth of the incorporation level lasted for at least 40 hours. For all precursors under study the incorporation rate into the cell biopolymers at the initial stages of cultivation was higher at 37 degrees C, than at a lower temperature. PMID- 11210627 TI - [Effect of cultivation temperature on nucleic acid level in bacteria Listeria monocytogenes and Yersinia pseudotuberculosis]. AB - The relationship between the multiplication of bacteria, the content of nucleic acid and the specific rate of their growth during their batch cultivation in nutrient broth and mineral medium at temperatures of 37 degrees C and 4-6 degrees C was studied in the causative agents of saprozoonotic infections with L. monocytogenes and Y. pseudotuberculosis used as typical representatives of such bacteria. The content of DNA was shown to remain practically unchanged after the alteration of cultivation temperature and the conditions of nutrition. The linear relationship between the content of RNA and specific growth rate was registered both at 37 degrees C and 4-6 degrees C. However a higher content of RNA at low temperatures was found to correspond to one and the same specific growth rate, which was linked with the additional synthesis of this nucleic acid. PMID- 11210628 TI - [Effect of hydroxylamine hydrochloride on lipopolysaccharide fatty acid composition in Shigella dysenteriae 1]. AB - Changes in the fatty acid composition of S. dysenteriae 1 lipid A after the treatment of lipopolysaccharide (LPS) with hydrosylamine hydrochloride (HH) and 4 degrees C, 37 degrees C and 56 degrees C were studied with the use of gas-liquid chromatographicmass-spectrometry. The treatment with HH led to a decrease in the toxicity of LPS, but produced no changes in the content of the main fatty acid components of lipid A (lauric, myristic, oxymyristic and palmitic acids). At the same time the total number of minor fatty acid derivatives decreased from 11 (in the original LPS) to 5 in LPS treated with HH at 56 degrees C. PMID- 11210629 TI - [Vibrio cholerae O139 bacteriophages]. AB - Cholera bacteriophages have been isolated from 27 lysogenic cultures of V. cholerae O139. As shown the pages under study belong to two morphological groups A1 and F1 and serological types II and XII. The use of prophage typing and the sensitivity test to specific phage made it possible to differentiate V. cholerae strains, serogroup O139. PMID- 11210630 TI - [Role of modern factors in the interaction between men and microorganisms. Importance of the national health system for prophylaxis and treatment of infectious diseases]. PMID- 11210631 TI - [Prospective observation of pyo-septic infections in frame of epidemiologic surveillance]. AB - The main principles of prospective observation in cardiosurgical hospitals have been worked out. The method of dynamic observation on hospital pyo-septic infections (HPSI) has shown its high effectiveness and permitted the more complete and timely detection of morbidity, as well as the determination of the groups and factors of risk. In the process of prospective observation and the timely realization of epidemic control measures a considerable decrease in HPSI morbidity has been achieved. PMID- 11210632 TI - [Immunosuppressive components of extracellular polysaccharide from Pseudomonas aeruginosa clinical strains]. AB - The immunosuppressive activity of lipopolysaccharide (LPS) contained in filtrates of newly isolated P. aeruginosa cultures was studied. The experimental model of delayed hypersensitivity to non-bacterial antigen in CBA mice and gel filtration through Sephadex G-200 were used. In addition to the already known LPS component with direct immunosuppressive action and having a mol.wt. of 150-800 kD, a new component was detected. It was found to be in inactive state and could be activated by redox treatment, thus becoming capable of inducing capacity for immunosuppression in Escherichia coli. This component had a mol.wt. of 50-70 kD and lost its activity after heating. PMID- 11210633 TI - [Impaired immune response associated with ABO antigen system in patients with purulent abscesses and dysentery]. AB - On the basis of a considerable number of facts--the results of the immunological survey of 197 patients with purulent infections of soft tissues and 103 shigellosis patients--the character and manifestation of immunological disturbances were found to depend on the genetic markers of blood (antigens of the AB0 system) which proved to differ in different type of pathology in patients. PMID- 11210634 TI - [Production and characterization of monoclonal antibodies to group-specific antigenic determinant of group A streptococcal polysaccharides]. AB - Hybridomas producing monoclonal antibodies (McAb) to group A streptococcal polysaccharide (A-PS) were obtained. Of these, 3 clones were selected: 2 clones producing IgG3, precipitating McAb and 1 clone producing IgM nonprecipitating McAb. The results of the competitive inhibition in the enzyme immunoassay suggested that precipitating and nonprecipitating McAb reacted with nonidentical epitopes of A-PS, though determinants, specifically reacting with the given McAb, had a common site which included N-acetyl-D-glucosamine. On the surface of bacteria, in addition to protein M, the presence of the given determinants of A PS was established in the direct immunofluorescence test. The newly developed method of direct immunofluorescence with the use of specially selected precipitating McAb was the basis for the development of rapid diagnosticum, permitting the identification of group A streptococci. PMID- 11210635 TI - [Intensity of the humoral immune response to herpesviruses as an indicator the body immune deficiency]. AB - The state of the local immunity system of the oral cavity was studied by the level of saliva immunoglobulins in patients with different processes on their mucous membranes: herpetic infection, respiratory allergosis and malignant tumors of the mouth cavity and the laryngopharynx. The suppression of the production of sIgA, was accompanied by the enhanced production of antibodies to the most widespread herpesviruses (herpes simplex virus, cytomegalovirus and Epstein-Barr virus). The maximum levels of serum IgG to herpesviruses were determined in patients with malignant tumors. The role of herpesviruses in the pathogenesis of immunodeficient states is discussed. PMID- 11210636 TI - [Immunocorrective effect of proteolytic enzymes on antibody genesis in mice subjected to infectious burn trauma and treatment with antibiotics]. AB - As revealed in this study, massive burn trauma manifestly suppresses the genesis of antibodies to T-dependent antigen (sheep red blood cells). The administration of ampicillin to the burned animals enhances immunosuppression, while gentamicin produces no essential impact on immune processes under these conditions. Proteolytic enzymes, terrilytin and terridecase, have corrective influence on disturbances in immune response in animals with burns. Enzyme in the immobilized form (terridecase) has a more pronounced immunotropic activity in this type of pathology. PMID- 11210637 TI - [Skin microbiocenosis in patient with chronic dermatoses]. AB - The skin microflora of patients with chronic dermatoses (atopic dermatitis and psoriasis) have been studied by the original "Bactotests" method. The data thus obtained indicate that the clinical picture of the disease is related to the severity of skin dysbacteriosis. The electron-microscopic study of 2 staphylococcal strains isolated from patients has revealed the presence of the immunoglobulin cover (capsule-like outer sheath consisting of immunoglobulins and other humoral protective factors) on the cell wall of these bacteria. PMID- 11210638 TI - [Effect of bifidobacteria and lactobacillus and antibiotics in combination with common gnotobiological isolation on the survival of mice with acute radiation sickness]. AB - The influence of the combined use of bacterial preparations (Bifidobacterium and Lactobacillus) and antibiotics (ciprofloxacin, lomefloxacin and amikacin) on the survival rate of irradiated mice placed under the conditions of general gnotobiological isolation was studied. Bacterial strains used in combination with quinolones (ciprofloxacin, lomefloxacin) significantly increased the mean survival time of the animals (p < 0.05) when introduced in a dose of 1.0 x 10(9) microbial cells per mouse on days 1, 3, 5, 7, 9, 11, 13 and 15 after irradiation. At the same time a short course of treatment with bacterial preparations (two injections on days 5 and 7 after irradiation) proved to be insufficient for increasing the survival rate of the animals. The mean survival time of the irradiated mice was higher after the use of bacterial preparations in combination with lomefloxacin or ciprofloxacin than after their use with amikacin. PMID- 11210639 TI - [Use of loading doses of bifidumbacterin forte for treatment of patients with acute enteric infections]. AB - The clinical observation of patients with acute enteric infections (AEI), treated with loading doses of Bifidumbacterin forte during the first 2 days of the disease, was carried out. The preparation was shown to produce a positive effect on the course of AEI: salmonellosis, alimentary toxicoinfections, acute, dysentery. The early decrease of the manifestations of intoxication, pain syndrome, diarrhea, as well as the acceleration of convalescence in comparison with standard treatment, were noted. The most essential dynamics was registered in salmonellosis patients. The analysis of clinical results allowed to recommend the use of loading doses of Bifidumbacterin forte, a probiotic with high colonization potential to normalize the microbiocenosis of the intestine in AEI. PMID- 11210640 TI - [Pathogenicity factors of Corynebacterium diphtheriae circulating in the Primorski region under conditions of mass immunization of population]. AB - The study of the main pathogenicity factors of C. diphtheriae (adhesive activity, toxigenicity, detection of tox+ gene) circulating in the Primorski Territory has been made. As revealed in this study, at the period of declined epidemic process due to mass immunization of the adult and child population against diphtheria the selection of C. diphtheriae strains with weak toxigenicity and low adhesiveness was observed. No strains having tox+ genes have been detected among C. diphtheriae nontoxigenic strains circulating in the Primorski Territory. PMID- 11210641 TI - [Identification of nontuberculous mycobacteria by methods of molecular biology]. AB - A number of clinical and laboratory strains of microorganisms belonging to different species of mycobacteria of the nontuberculous complex were tested with the use of the polymerase chain reaction and the restriction analysis. The unique restriction profiles of the following species of mycobacteria have been obtained: M. fortuitum VI, M. kansasii I, M. intracellulare, M. avium. PMID- 11210642 TI - [Computer-controlled maintenance of the dissolved oxygen level in a medium during controlled cultivation of Neisseria meningitidis]. AB - A new method for controlling the processes of N. meningitidis cultivation by the content of oxygen dissolved in the medium with the use of a computer, including the software, technical and methodological provision of the computer-operated control system, has been developed. The processes of the cultivation of N. meningitidis, groups A and B, under fully controlled conditions have been realized. The computer-operated control of the content of oxygen in the medium, the most important parameter of the process, has been shown to be essentially more effective than manual control. Information, accumulated in the course of the experiment, may be used in future for correction of mathematical models and optimization of the process. This will by necessary for obtaining biomass with predetermined properties in the development of new diagnostic and vaccine preparations. PMID- 11210643 TI - [Effect of Actoflor preparations on survival of Escherichia coli M-17 and Salmonella enteritidis under starvation conditions in mixed cultures]. AB - The viability of E. coli M-17 and S. enteritidis under starvation conditions in mono- and mixed cultures was studied. E. coli M-17 showed greater capacity for survival in mixed cultures than in monocultures, while for S. enteritidis the contrary was true. Preparations "Actoflor" enhanced the antagonistic activity of E. coli M-17, ensuring its absolute selective advantage under starvation conditions in mixed cultures. The role of E. coli M-17 low-molecular exometabolites is discussed; they are probably an important factor in the antagonistic activity of these microorganisms. PMID- 11210644 TI - [Industrially produced eubiotics as materials for isolation and study of DNA]. AB - The optimum and available methods for the isolation of DNA from bacteria, used as the basis of the industrial manufacture of eubiotics (colibacterin, lactobacterin, biobactone) have been developed. The proposed approach makes it possible to isolate DNA, suitable for genosystematic studies under laboratory conditions, directly from producer strains. PMID- 11210645 TI - [Effect of preparations of protein Yop encoded by Yersinia pestis calcium dependence plasmid on mice]. AB - The impact of the preparations of Y. pestis secreted proteins Yop (YopH-M, YopB, YopD-N, YopE) on mice immunized with 3 s.c. injections was studied. Though these proteins failed to protect the animals from plague, they stimulated the immunobiological transformation in the immunized animals. YopB and YopD-N were found to have the highest immunobiological activity with respect to mice. The preparation of YopB induced the production of the highest titers of specific antibodies and stimulated cell-mediated immune response. The injection of YopD-N to mice led to a considerable decrease in the proliferative capacity of splenocytes in vitro in response to stimulation with nonspecific mitogen ConA, as well as to pathological changes in the kidneys. PMID- 11210646 TI - [Synthesis of protective antigens during submerged cultivation of Vibrio cholerae]. AB - The effectiveness of dot immunoanalysis for evaluating the dynamics of the synthesis of O-antigen, cholera toxin, neuraminidase, adhesin CFA1 in the process of the reactor cultivation of V. cholerae used for the production of oral chemical cholera vaccine is shown. The established regularities of the synthesis of the protective antigens of V. cholerae in the process of scaled-up cultivation are discussed. PMID- 11210647 TI - [Bactericidal properties of hemo-cytolysin from Vibrio cholerae non O1 P-11702 strain in a panel of indicator cultures for detection of vibriocins]. AB - The influence of the preparation of hemo-cytolysin, obtained from V. cholerae non O1 strain P-11702 and inducing lysis of both red blood cells and V. cholerae cultures using a panel of indicator cultures for the detection of vibriocins, was studied. The set of indicator cultures contained 2 Shigella flexneri strains, 1 S. dysenteriae strain, 3 S. sonnei strains, 3 Escherichia coli strains and 2 V. cholerae strains, one of them being atypical. Hemo-cytolysin exhibited lytic activity with respect to S. dysenteriae, S. sonnei strains and 1 V. cholerae strain. i.e. to 4 out of 11 indicator strains. V. cholerae atypical strain proved to be resistant to the preparation in contrast to 33 V. cholerae typical strains, studied previously. PMID- 11210648 TI - [Comparison of various PCR methods for the detection of Chlamydia trachomatis, Ureaplasma urealyticum, and Mycoplasma hominis in women with impaired reproductive function]. AB - The comparative evaluation of the PCR test "Polimik" (Research and Production Firm "Litekh", Moscow) and the PCR test of the Novosibirsk Institute of Bioorganic Chemistry (NIBC) was carried out. The results obtained with the use of the PCR test "Polimik" and the PCR test of the NIBC of the detection of C. trachomatis and M. hominis coincided in 97.8% and 97.4% of cases. For U. urealyticum, the coincidence of the results of both PCR tests was 81.2%. Among women who visited gynecologists for reproductive function disturbances, the use of the PCR tests made it possible to detect C. trachomatis in 19 (5.5%) out of 343 cases, U. urealyticum in 96 (39.0%) out of 246 cases and M. hominis in 25 (16.9%) out of 148 cases. The results of the investigation revealed that the occurrence of C. trachomatis infection in Novosibirsk was comparable with that in other regions of the world among the low-risk groups of the population. The detection frequency of M. hominis and U. urealyticum with the use of the PCR tests showed that the occurrence of infections caused by these causative agents coincided with the data obtained in other countries. PMID- 11210649 TI - [Search for biological remedies for fungi of the Candida genus]. AB - 51 bacterial strains were studied with a view to find out anticandidial activity; of these, 15 strains were found to have activity, more on less expressed with respect to fungi of the genus Candida. In most cases the anticandidial activity of an antagonist strain was manifested to a similar degree against several Candida strains. The preliminary analysis of antifungal substances produced by microbial strains makes it possible to suggest their antibiotic nature. PMID- 11210650 TI - [Improving a process of cultivation of bifidobacteria in a bioreactor to obtain lyophilized seed culture]. AB - The parameters of the cultivation process and the characteristics of the culture growth have been analyzed. The phases of the population growth have been determined. The existence of short stages differing in the physiological state of the cells, their resistance to damaging factors and metabolic activity within the deceleration phase of the growth of bifidobacteria has been experimentally substantiated. To harvest the biomass, the period of the completion of the cultivation process has been chosen. The lyophilized seed culture in which a high percentage of viable cells is preserved for one year has been obtained. PMID- 11210652 TI - [Russia at the final stage of eradication of poliomyelitis]. PMID- 11210651 TI - [Bioterrorism: national and global threats]. PMID- 11210653 TI - [Implementation of the federal law of the Russian Federation "On immunoprophylaxis of infectious diseases" (vaccination against hepatitis B in Krasnoiarsk region )]. PMID- 11210654 TI - [PCR test systems for genetic identification of enterohemorrhagic Escherichia coli]. AB - The analysis of modern data on the development of amplification test systems for the gene indication of enterohemorrhagic E. coli (EHEC) is presented. In this work the emphasis is laid on the importance of using specific primers whose nucleotide sequence is closely linked with genes controlling the key factors of EHEC pathogenicity; these factors include the determinants of the synthesis of adhesins and invasins (bfp, eae, tir), shiga-like toxins (stx1, stx2), enterohemolysin (ehx), serine protease (epsA) and specific LPS of O-antigen (rfb). The problem of using primers whose sequence is not linked with virulence genes, but which may also be used for the gene indication of E. coli O157:H7 (uid, fliC) is discussed. PMID- 11210655 TI - [Pathogenicity of Burkholderia pseudomallei: extracellular and surface antigen functions]. AB - The data of literature and the results of investigations carried out by the authors on the analysis of B. pseudomallei pathogenicity factors. They include mucoid, endotoxin, lecithinase, proteases, hemolysins, etc. In addition to fimbriae and pili, the adhesive properties of B. pseudomallei are supposed to be associated with surface capsule-like structures whose composition includes Ag8. The characterization of exoproteases, hemolysins and lethal toxins is given. The virulence and immunogenicity of B. pseudomallei were shown to be linked with the components of surface glycoprotein Ag8. The conclusion has been made that the analyzed pathogenicity factors are of importance for deciphering the pathogenesis of melioidosis. PMID- 11210656 TI - [Factors contributing to preservation of Vibrio cholerae in water reservoirs]. AB - The summarized data of literature concerning the survival of V. cholerae in the environment and the influence of abiotic and biotic factors on this process are presented. These data make it possible to regard cholera as sapronosis and to form an idea of the role of factors contributing to the survival of V. cholerae in the environment and to its spread among human population. PMID- 11210658 TI - [Semeiology, examination and diagnosis of lesions of the oral mucosa]. AB - Tracking down the oral mucosa lesions require precise interrogation and cervico facial, buccal and general examination. Diagnosis needs more often biopsy if not contra-indicated. The opportunity of further examinations and tests is discussed. PMID- 11210657 TI - [Nosologic descriptions of lesions of the oral mucosa]. AB - This article describes extensively and systematically oral mucosa diseases. Macroscopical aspects are particularly described in order to give the dentist all important elements of differential diagnosis. This nosological description is based on a clinical approach: white and pigmented lesions are distinguished from ulcerated and benign so as malignant tumoral lesions. Specifically on the oral mucosa located lesions and oral mucosa lesions of systemic diseases are described. PMID- 11210659 TI - [The role of the dentist in the diagnosis, screening and followup of lesions of the oral mucosa. AB - The early detection and follow up of oral mucosa lesions are a must for every dentist. The importance of these activities is tremendous for oral cancerous and precancerous lesions, so every dentist is officially responsible for this important role in the public health. The modalities of such early detection and follow up are described. PMID- 11210660 TI - [Principles and therapeutic elements of lesions of the oral mucosa]. AB - The management of lesions of the oral mucosa requires precise knowledges and expertise in clinical care. This review article summarise the principles of the most validated therapeutical features about lesions of the oral mucosa. Global management procedures are described. Therapeutic modalities involving drugs, surgery, radiotherapy, chemotherapy, immunotherapy, electrotherapy, gene therapy and photodynamic therapy are detailed as well. PMID- 11210661 TI - Role of uncondensed 1,2,4-triazine compounds and related heterobicyclic systems as therapeutic agents--a review. AB - The role of uncondensed 1,2,4-triazine compounds and related heterobicyclic systems in AIDS and Cancer is reviewed. Their medicinal applications are also reported. PMID- 11210662 TI - Some reactions of 2-cyanomethyl-3-methyl-3H-imidazo[4,5-b]pyridine with isothiocyanates. Antituberculotic activity of the obtained compounds. AB - Some reactions of 2-cyanomethyl-3-methyl-3H-imidazo[4,5-b]pyridine with isothiocyanates were carried out. New derivatives of imidazo[4,5-b]pyridine with different substituents in 2-position and derivatives of the new pyrido-imidazo thiazine ring system were synthesized. Most of the obtained compounds were tested for their in vitro antituberculotic activity. PMID- 11210663 TI - Polysubstituted pyrazoles, Part 4: Synthesis, antimicrobial and antiinflammatory activity of some pyrazoles. AB - As a continuation of an earlier interest in polysubstituted pyrazoles, the synthesis of some derivatives of 1H-pyrazol-4-yl-2-oxo-but-3-enoic acid and ethyl 4-hydroxy-1H-pyrazole-3-carboxylates of potential antimicrobial and antiinflammatory activity is described. One compound showed in vitro antibacterial activity and two compounds displayed in vivo antiinflammatory potency in rats. PMID- 11210664 TI - Structure activity relationship of antiproliferative N-acyl-aspartic acid dimethyl ester. 2. Variation of the aspartyl moiety. AB - Structural variations of the L-aspartic acid substructure of (S)-N-3 phenoxycinnamoylaspartic acid dimethyl ester which shows a selective antiproliferative activity against THP-1 tumor cells, demonstrated that the L aspartic acid moiety is absolutely mandatory for antiproliferative activity as well as for selectivity. PMID- 11210665 TI - [Intramolecular alkylation of aromatic compounds. 35. Di- and tetrahydropyridinemethylindolines as potential precursors of ergolines] . AB - In the presence of methyl chloroformate, compound 6a is reduced by NaCNBH3 yielding the 1,6-dihydropyridine derivative 7. Under the same conditions the indoline 10 accessible from 6a via 9a gives a mixture of the 1,4- and 1,6 dihydropyridine derivatives 11 and 12. As by-product of the reduction the borane adduct 13 is detected. In contrast the methoiodide 1 is reduced by NaBH4 or DIBAH giving a separable mixture of the diastereomers of the tetrahydropyridines 2 and 3; on catalytic hydrogenation the piperidine derivative 4 is formed. Cleavage of the enolether moiety in 3a and 7 provides the corresponding piperidones 5 and 14, respectively. Using prolonged reaction time 7 is hydrolized quantitatively furnishing the 1,4-diketone 15. PMID- 11210666 TI - Fluorine-containing heterocycles: synthesis and some reactions of new 3-amino-2 functionalized-6-(2'-thienyl)-4-trifluoromethylthieno [2,3-b]pyridines. AB - 3-Cyano-6-(2'-thienyl)-4-trifluoromethylpyridine-2(1H)-thione (2) was prepared and reacted with chloroacetone or phenacyl bromide to yield the 2-acetyl or benzoyl-3-amino-6-(2'-thienyl)-4-trifluoromethylthieno[2,3-b]pyridines (3a, b). In contrast, the reaction of 2 with chloroacetamide or its N-aryl derivatives gave the corresponding 2-carbamoylmethyl thiopyridines 4a-c. Upon treatment of these educts with K2CO3 or C2H5ONa in ethanol, they underwent intramolecular Thorpe-Ziegler cyclization to afford 3-amino-2-carbamoyl-6-(2'-thienyl)-4 trifluoromethyl-thieno[2,3-b]pyridine (5a) and its N-aryl analogs 5b, c. Compounds 5a-c underwent some reactions to yield new pyrido[3',2':4,5]thieno[3,2 d]pyrimidines and pyrido[3',2':4,5]thieno[3,2-d][1,2,3] triazines. PMID- 11210667 TI - Stability of several LHRH antagonists against proteolytic enzymes and identification of degradation products by mass spectrometry. AB - In this study stabilities of several LHRH antagonists against proteolytic enzymes are compared. For the enzymatic tests 15 proteases which differ in both substrate specificity and pH optimum were selected. The cyclic and two linear antagonists proved to be extraordinarily stable against the enzymes used over an incubation time of 50 h. Some degradation products were identified by high-performance liquid chromatography combined with mass spectrometry. PMID- 11210668 TI - Film formation, reproducibility of production and curing with respect to release stability of functional coatings from aqueous polymer dispersions. AB - The formation of film coatings from aqueous polymer dispersions is a complex process, highly dependent on additives and process parameters. Release instability of modified release coatings from aqueous polymer dispersions is a frequently described problem that hinders the general application of such dispersions. However, if some important prerequisites are fulfilled, storage stability should be achievable. Most important are: (a) The appropriate plasticizing time has to be considered, incorporating sparingly soluble plasticizers in the dispersion. (b) Necessary pore formers increase the permeability of the coating to a desired and constant extent only if they are compatible with the polymer. (c) Coating in the fluidized bed at or slightly above the minimum film forming temperature may lead to only incomplete film formation. Curing at higher temperatures improves the polymer particles coalescence to a physically stable state. Other stability aspects such as physical and chemical aging, migration of plasticizers and drugs and incompatibilities are also discussed. PMID- 11210669 TI - Rapid and simple method for detection of fenofibric acid in human serum by high performance liquid chromatography. AB - A sensitive HPLC method for the determination of fenofibric acid (FA), the active form of fenofibrate in serum is described. FA from human serum samples was isolated by an easy one-step extraction procedure with a mixture of n-hexane and ethylacetate (90:10, v/v). The recovery was 84.8% of the total Fa in serum. The compound was separated isocratically on a reversed phase with acetonitrile and 0.02 M phosphoric acid (55:45, v/v) at a flow-rate of 1.0 ml/min. Absorbance at 287 nm was recorded for quantification. Validation presents a detection limit of 0.03 microgram/ml and a quantification limit of 0.1 microgram/ml (relative standard deviation at 0.1 microgram/ml = 7.1%). For an extensive validation of this method we determined the serum levels of FA in one young male volunteer and examined the pharmacokinetics of standard, mikronized and slow release formulation of fenofibrate after oral intake. This method is a rapid and reliable tool for quantitative determination of fenofibric acid in pharmacokinetic investigations. PMID- 11210671 TI - [Separation of oxetacaine and its metabolites] . AB - Oxetacaine (1), known as Tepilta, may be biotransformed to 2-5. After having tried to separate 1-5 by GC we succeeded in finding the HPLC method on Silicagel Si 60 with the eluent MeOH/TBME/HClO4. PMID- 11210670 TI - Absorbance data of hypericin and pseudohypericin used as reference compounds for medicinal plant analysis. AB - The evaluation of the absorbance data of hypericin and pseudohypericin revealed the molar/specific coefficients of absorbance in methanol-pyridine (99:1, v/v) at the maximum of the longest wavelength to be 51936/1030 and 43486/836, respectively. The absorbance data of hypericin were also determined in methanol. They were not significantly different from those in the presence of pyridine. The decrease of the coefficients by water addition was found to be the same for hypericin and pseudohypericin. It was concluded that hypericin and pseudohypericin reveal the same homoassociation behavior. PMID- 11210672 TI - Scaling up feasibility of the production of solid lipid nanoparticles (SLN). AB - Solid lipid nanoparticles (SLN/Lipopearls) are widely discussed as colloidal drug carrier system. In contrast to polymeric systems, such as polylactic copolyol capsules, these systems show up with a good biocompatibility, if applied parenterally. The solid lipid matrices can be comprised of fats or waxes and allow protection of incorporated active ingredients against chemical and physical degradation. The SLN can either be produced by "hot homogenisation" of melted lipids at elevated temperatures or a "cold homogenization" process. This paper deals with production technologies for SLN formulations, based on non-ethoxylated fat components for topical application and high pressure homogenization (APV Deutschland GmbH, D-Lubeck). Based on the chosen fat components, a novel and easy manufacturing and scaling up method was developed to maintain chemical and physical integrity of encapsulated active and carrier. PMID- 11210673 TI - Studies on dressings for oral cavity mucosa. Part 5: Properties of xerogel stomatological dressings with one-side antiadhesive coating. AB - The adhesion of xerogel dressings based on Eudragit (E), and methylcellulose (Mc) is in within the range of 143-270 g, and dissolution time of xerogel dressings in water is 3.4 h, and in artifical gastric juice 2.8 h. The 50% release time for Kunitz protease inhibitor ranges from 3.2-11.5 h. PMID- 11210674 TI - Long-term stability characterization of a controlled release gastrointestinal therapeutic system coated with a cellulose acetate pseudolatex. AB - The objective of the present study was to study the long term effects of storage of osmotically controlled gastrointestinal therapeutic system (GITS) in exaggerated conditions of temperature and humidity. Bilayered osmotic tablets were obtained with atenolol, Polyox N80, Carbopol 934P and magnesium stearate in one layer, and Polyox 303, Carbopol 974, sodium chloride and magnesium stearate in the other layer. A customized cellulose acetate (CA) pseudolatex was used to provide semipermeable housing around the tablet and an orifice was drilled into the drug layer to obtain the Atenolol GITS. The GITS were stored at 4 degrees C (refrigeration), 25 degrees C, 37 degrees C, 45 degrees C, 55 degrees C, 37 degrees C/11% RH, 37 degrees C/51% RH, and 37 degrees C/91% RH. Quantitative X ray diffraction and dissolution studies were performed at regular intervals for one year. Aqueous CA polymeric film formation continued in GITS stored at higher temperature by gradual evaporation of moisture and coalescence of polymer. At lower temperatures atenolol crystallinity increased with time, but at higher temperatures the crystallinity was decreased. At higher humidity, a decrease in crystallinity was observed. A decrease in dissolution rate and extent was observed at higher temperature and higher humidity conditions. Exaggerated temperature and humidity conditions affected the dissolution profile by modifying the CA pseudolatex membrane and crystallinity of atenolol. PMID- 11210675 TI - Penetration of verapamil hydrochloride in the presence of sodium glycocholate as penetration enhancer through mucous membrane. AB - A model buccal drug formulation (BDF) with verapamil hydrochloride (VH) is in the form of a thin elastic disk made of two layers. The aim of this paper was to determine the influence of sodium glycocholate (SG) as a penetration enhancer in a BDF on the in vitro penetration rate of VH through pig oesophageal mucosa. It was found that VH penetrates mucosa. In 6 h 10.35 mg/cm2 of drug diffused from saturated solution in a buffer of pH 5.3 white from diffused only 7.78 mg/cm2 and 4.68 mg/cm2 of VH, respectively saturated buffers of pH 6.8 and 7.3. In 6 h approximately 1.3 mg/cm2 of VH penetrate the mucosa from the control BDF model which does not contain the penetration enhancer. Conversely the content of SG in the model BDF contributes to the increase in drug penetration rate. PMID- 11210676 TI - Effect of gonadectomy on cyclosporine pharmacokinetics in male and female rats. AB - The present paper reports about the effect of gonadectomy on cyclosporine (CyA) pharmacokinetics in rats. The oral administration of CyA (10 mg/kg b.w.) to male rats caused two-fold higher drug blood levels than those reached by females at 24 h after the last dose (334.10 +/- 126.70 vs. 161.49 +/- 53.39 ng/ml, p < 0.05). These levels increased by about 25% in orchiectomized male rats (419.47 +/- 132.63 ng/ml) but they returned to control values after testosterone treatment (330.99 +/- 130.80 ng/ml). On the other hand, CyA blood levels (90.66 +/- 22.25 ng/ml) decreased after ovariectomy, even more in the case of gonadectomized female rats receiving estradiol replacement (67.83 +/- 24.15 ng/ml). With regards to drug distribution, the concentrations of CyA in the liver, the kidneys and the spleen at 24 h after the last dose were about 8, 5 and 6-fold higher than blood levels, respectively, regardless of animal gender. These partition coefficients were increased to 11, 7 and 9-fold by male castration suggesting a more extensive drug distribution. Contrariwise, drug tissue levels in ovariectomized rats decreased. The changes of drug blood and tissue levels among groups were not associated to the variations of metabolite concentrations in the liver or blood. Therefore, gonadectomy exerts a complex effect on CyA pharmacokinetics in rats and makes complementary studies necessary to clarify how differences in sexual hormone secretion alter CyA disposition. PMID- 11210677 TI - Photosensitizing activity of thiocolchicoside: photochemical and in vitro phototoxicity studies. AB - The phototoxic drug thiocolchicoside (2-dimethoxy-2-glucosidoxythiocolchicine, 1), is photolabile under irradiation with UV-A light from TL 100 W-P Philips bulbs (at lambda max 355 nm) light and also with a N2 laser (at 337 nm) in aerobic and anaerobic conditions. Irradiation of a methanol solution of 1 produces two photoproducts without a glucoside group. One of these lost the methylthio-group, while the other is oxidized (only under aerobic conditions) to sulfoxide. The formation of singlet oxygen by photolysis of 1 was evidenced by trapping with 2,5-dimethylfuran (GC-MS), furfuryl alcohol, 1,3-cyclohexadiene-1,4 diethanoate (HPLC) and by the histidine test as 1O2 scavengers. Thiocolchicoside has been shown to photosensitize the reduction of nitro blue tetrazolium by direct electron transfer mechanism, when irradiated under the same conditions as for photolysis. Oxygen may also be involved in this electron transfer reaction to form the superoxide anion radical. Thiocolchicoside was screened in vitro in different concentrations for UV-Vis-induced phototoxic effects in a photohemolysis test, in the presence and absence of different radical scavengers, singlet oxygen and superoxide radical quenchers. In addition, 1 photosensitized the peroxidation of linoleic acid, monitored by the UV-detection of dienic hydroperoxides. Studies on peripheral blood mononuclear cells (lymphocytes) demonstrated phototoxic effects on them. Protection by GSH, DABCO, sodium azide and SOD are indicative of both Type I and II photosensitization pathways mediated by free radicals and singlet molecular oxygen. PMID- 11210678 TI - Effect of diazepam and midazolam on the antinociceptive effect of morphine, metamizol and indomethacin in mice. AB - The influence of midazolam and diazepam on antinociceptive effect of morphine (10 mg/kg), metamizol (500 mg/kg) and indomethacin (10 mg/kg) was investigated in a mouse model using the tail-flick and hot-plate tests. All drugs were injected intraperitoneally. Benzodiazepines were administered to mice 30 min before applying the analgesic drugs. Measurement of nociception was performed within 2 h after benzodiazepine administration. Diazepam at doses of 0.25 mg/kg and 2.5 mg/kg injected with morphine was found to decrease the antinociceptive effect of morphine. Similarly, diazepam decreased the antinociceptive effect of metamizol (only in the tail-flick test) and indomethacin. Midazolam used at doses of 1.25 mg/kg and 2.5 mg/kg decreased the antinociceptive effect of morphine, metamizol (only in the tail-flick test) and indomethacin. PMID- 11210679 TI - Effect of the aqueous extract of Rumex patientia on xylol and hyaluronidase induced capillary permeability compared to indomethacin. AB - In this study, the effect of an aqueous extract of Rumex patientia L. (Polygonaceae) (D-1) on capillary permeability which was induced by xylol and hyaluronidase was investigated. Experiments were conducted on rabbits according to Monakova and Matusis methods. The effects of D-1 were compared to those of indomethacin, which was used as a control throughout the experiment. Both D-1 (100 mg/kg) and indomethacin (10 mg/kg) were administered orally. As a result, D 1 inhibited capillary permeability, which was induced by xylol and hyaluronidase, and it was found that it was as effective as indomethacin. PMID- 11210680 TI - Flavonoids of Melaleuca quinquenervia. AB - From the leaves of Melaleuca quinquenervia (Clav.) S. T. Blake, the new flavonoid 5,7,3',4'-tetrahydroxyflavone 2'-O-beta-D-glucopyranuronide, as well as eight known flavonol glycosides have been isolated and characterized. The structures were established by chromatography, chemical degradation and UV spectroscopy and confirmed by ESI-MS and NMR spectroscopy. This is the first report on the isolation and identification of these flavonoids in the genus Melaleuca. PMID- 11210681 TI - Grids and high kilo-volt-peak-setting in bedside chest radiographic examinations. AB - Bedside chest radiographic examinations in intensive care units with grids are impaired by artefacts caused by angulation of the grid (grid cut-off). Two different grids--a grid with a high strip density of 70 lines per cm and the "InSight portable imaging system"--were examined in an intensive care unit with respect to their susceptibility to angulation, image quality and handling of the grid. Five radiologists compared 50 radiographs of each grid considering ten image quality criteria. Using the "InSight portable imaging system" major artefacts were undetectable even at an angulation of 10%; no adjustment of the grid was required, which reduced the amount of time needed to take the radiograph by 26%. The increase in dosage demanded by the employment of the grids at low kilovolt peak setting could be partially compensated by the use of high kilovolt peak setting. The image quality of the "InSight portable imaging system" together with a high kilovolt peak setting is satisfactory, and due to its simplified handling, the portable imaging system has proved to be suitable for bedside chest radiography in intensive care. PMID- 11210682 TI - A pitfall of neck vessels Doppler ultrasound: left subclavian artery occlusion without vertebral steal syndrome. AB - In most cases, ostial occlusion of the subclavian artery induces a reversal of the blood flow in the ipsilateral vertebral artery. This hemodynamic diversion is obviously brought out by Doppler ultrasound of the neck vessels. Nevertheless, when the subclavian ostial lesions are less severe or in case of anatomical variations, the alterations of the vertebral flux are more discrete. An accurate Doppler examination is then required to avoid pitfalls. In the light of a particularly complex case, we reviewed the Doppler signs of vertebral blood flow in normal conditions and in patent or less obvious subclavian steals. PMID- 11210683 TI - [Use of dental CT software progarms (Dentascan) for optimal arthroscopic CT of knee menisci]. AB - The need for CT automated multiaxial programs of reconstruction, able to accommodate with complex curvilinear anatomic structures has recently been satisfied by Dental Software Programs--"DENTASCAN"--essentially developed for implantology. Taking advantage of the very close likeness of dental archs and menisci of the knee in terms of form--variable complex curvilinear structures- and size, our study shows the advantages of "DENTASCAN" program to optimize the study of the menisci with Spiral Arthro-CT (SACT). The results obtained on a series of 228 menisci are compared with Conventional Arthrography (CA). 11.85% of additional lesions are found with SACT and 30.2% of all lesions demonstrated by CA are also more adequately described by SACT associated with "DENTASCAN". Moreover, fissures and ulcerations of the tibio-femoral cartilages, undiagnosed by preliminary CA are found in 20, 8% of patients with SACT. We conclude that SACT is much more effective and reproducible than CA for the study of the knee and we promote the use of Dental CT Software Programs like "DENTASCAN" for the study of the femorotibial and meniscus complex. Additional work is now necessary to compare the effectiveness of SACT with MRI or arthro-MRI of the knee with valuation of arthroscopy. PMID- 11210684 TI - MR imaging of the shoulder: imaging techniques and anatomy. AB - Since the development of dedicated surface coils and the more widespread use of state-of-the-art arthrographic techniques, MR imaging of the shoulder has come to maturity. In this article the imaging techniques of conventional MR imaging and MR arthrography of the shoulder are reviewed. The complex anatomy, the many anatomic variations and diagnostic variants and pitfalls and discrimination of pathologic entities from normal findings are discussed. Familiarity with the normal anatomy is a prerequisite to achieve a high diagnostic accuracy in the detection of a variety of pathologic conditions of the shoulder joint. PMID- 11210685 TI - MR arthrography of the rotator cuff and capsulolabral complex. AB - MR arthrography of the shoulder has reached maturity in recent years. As opposed to conventional MRI of the shoulder it is less prone to artefacts frequently leading to equivocal interpretation. The spectrum of pathology in which MR arthrography has significant advantages is reviewed, with emphasis on the rotator cuff and the capsulolabral complex. PMID- 11210686 TI - [Intraluminal duodenal diverticulosis complicated by hemorrhage]. PMID- 11210687 TI - MR features of cavernous angioma. PMID- 11210688 TI - Dentin adhesives for the twenty-first century. AB - The efforts of numerous clinical scientists have resulted in the development of tooth bonding systems that have changed the way clinical dentistry is practiced. The adhesion between polymeric restorative materials and dentin has been optimized to the point that little improvement can be expected within the next decade or even more. Already, the adhesion between the two substrates is greater than the inherent tensile strength of dentin itself. Improvements however, will undoubtedly occur in the manner in which the materials are used clinically. Such achievements are necessary to standardize performance as well as to eliminate postoperative sensitivity. PMID- 11210689 TI - Esthetic post-and-core treatment. AB - The dilemma that confronts the practitioner in the area of post-endodontic rehabilitation is a positive one. The variety of products and techniques available offer practical solutions to most restorative problems. Patients have benefited [figure: see text] from recent developments in post-and-core technology, and continue to reap the benefits of research and development. The ideal system of products for the endodontic-restorative continuum includes: an esthetic resin fiber post a composite core an automixed resin luting cement current techniques that combine the automixed resin luting cement and composite core into the same component. PMID- 11210690 TI - Porcelain inlays and onlays. AB - Dentistry has been witness to tremendous changes in technology, introducing new techniques and materials. New procedures are being performed faster, are more reliable, are painless, and are more esthetic. These changes not only have been extremely motivational for dentists, but also for patients. Patients are aware that esthetic approaches in dentistry can change one's appearance, and are coming to the dentist willingly. PMID- 11210691 TI - Diagnosis and treatment planning for ceramic restorations. AB - Esthetic dentistry's intention is to deliver all phases of dentistry in a natural and attractive manner. Whether restorative and laboratory procedures or periodontal, orthodontic, or surgical procedures, ultimately the end results need to be natural in appearance and esthetically pleasing to the patient and dentist. The intention of this case study was to emphasize the relationship between the patient, dentist, and laboratory technician. The ability of all three to work efficiently demands incredible communication skills. A mutual respect in knowledge, desires, and skills creates the foundation to initiate this relationship. Communication skills and respect need to follow time-tested principles of restorative and prosthetic dentistry to be successful. PMID- 11210692 TI - Proportional smile design using the recurring esthetic dental (red) proportion. AB - Dentists have needed an objective way in which to evaluate a smile. A method for determining the ideal size and position of the anterior teeth has been presented here. Use of the FIVE to evaluate the RED proportion and the width-to-height ratio, tempered with sound clinical judgment, gives pleasing and consistent results. With the diversity that exists in nature, rarely does the final result follow all the mathematical rules of proportional smile design. This approach may serve as a foundation on which to base initial smile design, however. When one begins to understand the relationship between beauty, mathematics, and the surrounding world, one begins to appreciate their interdependence. PMID- 11210693 TI - Shades of a color. Illusion or reality? AB - Attaining the highest clinical level in esthetic and cosmetic dentistry necessitates the development of artistic skills; of balancing illusion with reality. The shade of a tooth is a combination of color and light and varies in different light conditions. Understanding the differences in color shades is the basis to creating illusions. Understanding light and color, and the reality of illusions, allows the clinician to design and sculpt a smile, to modify a flawed display artistically so that patients may perceive it as natural and more attractive, and to design laminates and veneers, class III, class IV, and cervical cavities. PMID- 11210694 TI - Occlusal function. Beyond centric relation. AB - With the emphasis placed on esthetics today, anterior guidance has an important role in the development of a stable, anatomic, functional, and esthetic result. To develop a predictable and stable result requires a multidisciplinary approach to esthetics and function. The orthodontist is a major contributor in helping the restorative dentist achieve the anatomic and functional harmony that is needed for long-term stable function and esthetics. Harmony in function creates long lasting smiles. In their continued quest for optimal results, and as members of their interdisciplinary teams, orthodontists should remind themselves of what Gottlieb wrote in 1986 in an editorial in the Journal of Clinical Orthodontics: "There is a difference between a beautiful alignment of teeth and an alignment of beautiful teeth. The orthodontist's job is not complete until there is a beautiful alignment of beautiful teeth." PMID- 11210695 TI - Implant-osseous osteotomy for correction of the misaligned anterior maxillary implant. AB - The trend has been to use angled abutments to compensate for implants that have poor emergence profiles. This trend has resulted in increasing unfavorable forces being placed on the implant, poor soft tissue emergence and contours, or creation of areas that the patient cannot maintain properly. The end results are an esthetic compromise and ultimately implant failure. This case illustrates that a misplaced or misaligned integrated implant can be repositioned successfully within the maxillary alveolus. Careful treatment planning, flap design, and soft tissue manipulation must be considered to maintain the vascularity and integration within the implant-osseous segment as well as the soft tissue. The byproduct of maintaining vascular integrity is normal soft tissue morphology, especially of the interdental papillae (see Fig. 6). PMID- 11210696 TI - Lasers and air abrasion. New modalities for tooth preparation. AB - Hard tissue lasers and air abrasion units have a place in the modern dentist's armamentarium. Speed, comfort, ease of approach, public relations, and patient appeal are some of the advantages. The dentist's own comfort and satisfaction, knowing that he or she is doing the best dentistry without frightening the already fearful patient, should help the dentist decide which one of the modalities to incorporate into his or her practice. PMID- 11210697 TI - Latest advances in laser systems and periodontal surgery. AB - The author explores the incipient role of laser technology in periodontics and general dentistry. A short history of laser use in dentistry is offered, and the clinical results of surgery on hard and soft tissues with different types of lasers are reviewed. PMID- 11210698 TI - Biocomposition and reaction of pulp tissues to restorative treatments. AB - Dentistry has experienced exponential growth in the biologic and physiologic knowledge of enamel, dentin, and pulp tissues. In one decade, material development has exceeded clinical testing limits, allowing their arrival to the commercial market without proper validation. This article clarifies the enigma of acid etching; explaining and clarifying the diverse opinions and issues of material toxicity between in vitro and in vivo usage test perspectives. This article also demystifies the biology of pulp healing regarding calcium hydroxide and adhesive systems to promote dentin bridge formation. Lastly, this article provides biologically lucid pulp exposure treatment regimens with agents such as NaOCl, allowing clinicians to increase their long-term clinical success. PMID- 11210699 TI - Contemporary posterior direct composites using state-of-the-art techniques. AB - The dental team that wishes to increase the use of posterior composite restorations will benefit greatly by the information and step-by-step techniques found in this article (Fig. 7A and B). Starting with a clean slate and analyzing the chemistries, the physical nature of resin-based composites, and the systems and devices available to use them most efficiently, the author presents a state of-the-art, evidence-based technique. By cutting out many of the steps that follow traditional methods with traditional materials and instruments for the placement of silver amalgam, sophisticated practitioners will readily understand the reasoning behind this successful, contemporary, direct posterior composite technique (Fig. 8A-J). PMID- 11210700 TI - Advances in restorative materials. AB - This article has presented basic up-to-date information concerning the selection, properties, and clinical uses of current restoratives that are tooth colored and adhesive. This area in dentistry is advancing at an exponential rate, and it is essential that all practitioners pay constant attention to the information about all materials as they appear on the market. Coupled with a thorough knowledge of treatment planning and case design, results such as seen in Figure 4 make restorative practice a rewarding endeavor for clinicians and patients. Interest in the scientific background, development, and performance of restorative materials must be at a high level to avoid being snared by advertising promises. PMID- 11210701 TI - Materials and techniques for achieving clinical excellence with indirect composite restorations. AB - Indirect resin restoration technology continues to grow at an unbelievable rate. This article has outlined some of the materials available within this category. There are others that the author has not had the opportunity to work with. At this time, the author believes the primary indication for the use of this class of material is esthetic inlays and onlays as well as a well-planned conservative [figure: see text] fixed partial denture in a low stress area. If unclear about the best material to use in a given situation, the dentist should consult the laboratory technician to discuss the technician's experience and confidence with the different systems. Many times the physical properties of the material are not as important as the ability of the technician and his or her experience with the different handling properties of the available systems when examining the short term and long-term success of the restoration. PMID- 11210702 TI - Creating tight, anatomically correct interproximal contacts. AB - Achievement of an excellent contact, one that provides a natural look and feel, reproducing the natural tooth contact or sometimes improving it, can be achieved in many ways. Understanding the separate issues of tightness and anatomy is crucial to achieving the desired result. In most cases, use of a contoured sectional matrix and McKean-style ring is the surest way to achieve the desired result. Unusual circumstances, such as wide preparations and malpositioned teeth, call for innovative techniques, some of which are illustrated in this article. PMID- 11210703 TI - [Ocular injuries and triage after the bombing attack on the United States embassy in Nairobi (Kenya)]. AB - BACKGROUND: As a result of the terrorist bombings of the United States Embassies in Daressalam (Tansania) and Nairobi (Kenya) on August 7, 1998, over 200 people were killed. 5000 persons were injured severely. The purpose of this article is to provide a review of our experiences in the evaluation and treatment of patients with multiple simultaneous ocular injuries sustained in the Nairobi attack. PATIENTS AND METHODS: We treated eight survivors of the assault, four of them with extremely severe eye injuries. A three-tiered system of triage developed. The first level occurred on scene, in which minor injuries were treated locally and more severe injuries were transported by aeromedical evacuation to Landstuhl Regional Medical Center (LMRC), in Germany among other locations. Surgical exploration of all patients arriving at LRMC was performed and surgical repair was undertaken when appropriate and technically possible. Patients requiring vitreoretinal surgery were transferred either to Saarland University Eye Hospital, Homburg, Germany, or Walter Reed Army Medical Center, Washington, DC. RESULTS: Only one eye required enucleation, due to an almost complete extrusion of the retina. It was possible to stabilize even severely injured eyes with multiple intraocular foreign bodies. CONCLUSIONS: Modern microsurgical techniques such as temporary keratoprothesis, perforating keratoplasty, and pars plana vitrectomy can now save eyes and often allow restoration of usuable visual acuity where this once have been deemed impossible. PMID- 11210704 TI - [Laser tyndallometry and monitoring of treatment in 20 children with juvenile uveitis]. AB - BACKGROUND: Treatment of children with juvenile uveitis requires adequate control of inflammation while minimizing systemic or ocular side effects. The study was performed to evaluate the potential use of the laser flare-cell meter in monitoring and adjustment of therapy in juvenile uveitis. PATIENTS AND METHODS: Retrospectively, we monitored 20 children (11 girls and 9 boys) with an age range from 3 to 15 years presenting with juvenile iridocyclitis (10/20), intermediate (5/20) or posterior (5/20) uveitis. During the follow-up period (median 25.2 months, range: 2 to 83 months) multiple clinical controls were performed. We recorded clinical data, present therapy, and measurements using the laser flare cell meter (Kowa FC-1000). RESULTS: Laser flare-cell meter measurements were easily obtained and highly reliable even in these young patients. During follow up, 36 recurrences of intraocular inflammation were detected in 19 eyes. Relapses of inflammation as well as a response to treatment were seen at an early stage. Semiquantitative observations of cells and aqueous flare in the anterior chamber, or visual acuity of patients were less reliable in predicting recurrences. CONCLUSIONS: Laser tyndallometry offers a reliable, examiner-independent method to assess intraocular inflammation in children with juvenile uveitis and to adjust the necessary treatment. PMID- 11210705 TI - [Air endotamponade in 52 vitrectomies due to proliferative diabetic retinopathy- retrospective comparison with 40 vitrectomies without endotamponade]. AB - BACKGROUND: In patients with proliferative diabetic retinopathy rebleeding after pars plana vitrectomy is one of the most common complications. We tried to reduce the rate of that complication by using an air endotamponade. PATIENTS AND METHODS: The following study is a retrospective comparison of 2 patient groups both after pars plana vitrectomy due to proliferative diabetic retinopathy. Group 1 was managed with air as endotamponade (n = 52, mean age 61.2 years), group 2 without any endotamponade (n = 40, mean age 59.4 years). Classification of the proliferative diabetic retinopathy as described by Kroll et al. [5] in both groups: 23 and 29 patients with stage A resp., 24 and 10 patients with stage B resp., 5 and 1 patient with stage C respectively. RESULTS: 77% of group 1 patients had an increase os vision by mean of 4.8 vision steps, in 70% of the group 2 patients vision increased by mean of 7.2 vision steps. Complications in both groups as follows: Rebleeding within 14 days 15% vs. 33%, development of secondary glaucoma in 9.6% and 17.5% resp., revitrectomy within 14 days were necessary in 3.8% resp. 2.5% of the patients, later revitrectomy in 13.5% vs. 42.5% of all patients. SUMMARY: Air endotamponade turned out to be appropriate to reduce the rate of postoperative vitreous rebleeding after pars plana vitrectomy due to proliferative diabetic retinopathy. We found no increase of secondary glaucoma or cataract. PMID- 11210706 TI - [Congenital nystagmus: indication, results and dosage of Kestenbaum surgery in 34 patients]. AB - BACKGROUND: Abnormal, nystagmus related head postures can be treated by Kestenbaum's procedure, if the concept of artificial divergence (Cuppers procedure) is not expected to work. In this retrospective study, we evaluated the effects of Kestenbaum surgery in order to establish dosage recommendations. PATIENTS AND METHODS: Solely patients who received Kestenbaum surgery (maximum 3 mm dosage difference between both eyes, i.e., without additional artificial divergence) for a horizontal head turn (HT) due to nystagmus were included in this study. Exclusion criteria were previous eye muscle surgery, strabismus, lacking binocular vision, and cerebral disease. The millimetres of surgery and the pre- and 3-6 months-postoperative findings (HT and visual acuity at 5 m distance, stereopsis) were evaluated. RESULTS: Of the 34 patients, 21 had a HT to the left side and 20 were male. The age at surgery (median, 10%- and 90% quantile) was 7 years (4-32), the total amount of surgery 32 mm (20-40), and the preoperative HT 30 degrees (20-40). Postoperatively (n = 31), the HT amounted to 7 degrees (0-20). The reduction of HT was 67% (25-100), the efficacy of surgery 0.8 degree (0.3-1.0) per millimetre total amount of surgery on both eyes together. Four patients needed further surgery due to residual HT. Postoperatively, the maximum visual acuity was available without HT or with significantly less HT than preoperatively. Stereopsis showed a trend of improvement. CONCLUSIONS: The Kestenbaum procedure has a dose/effect ratio similar to that of recess/resect surgery for strabismus. Due to a long term efficacy of 1.5 degrees/mm, a dosage (in millimetres) on each eye of two thirds of the HT (in degrees) can be recommended. Physiological and methodical factors (false measurements) have to be discussed as an explanation for apparently low efficacy of surgery. PMID- 11210707 TI - [Driving ability after reversal of phenylephrine 10% induced mydriasis by dapiprazole 0.5%; a prospective study on 65 eyes]. AB - BACKGROUND: Particularly outpatients want to reach the ability for driving a car as soon as possible after pupillary dilatation. Dapiprazole is an alpha-1 adrenergic inhibitor that antagonizes the mydriatic effect of phenylephrine in a direct competitive way. The aim of this study was to determine restoration of traffic related functions after dapiprazole application in accordance with the guidelines of the German Society of Ophthalmology (DOG). SUBJECTS: 65 eyes of 33 subjects were tested (17 females, 16 males). All had driving licenses without restrictions. Before mydriasis and after reversal with dapiprazole traffic related functions were evaluated (photopic visual acuity, mesopic vision, sensitivity to glare, colour vision, accommodation, visual field). RESULTS: No relevant changes of the parameter responsible for the ability to drive a motor vehicle could be shown after reaching premydriatic pupil diameters. CONCLUSIONS: There is evidence that reaching normal pupil diameters after reversal of mydriasis by dapiprazole is a valid sign of restoration of traffic related functions. PMID- 11210709 TI - [Significance of postoperative face-down positioning after surgery for idiopathic macular holes: consecutive case-control study]. AB - BACKGROUND: Postoperative face-down positioning is considered to be a critical part in macular hole surgery with short-acting gas. However, the significance of this posturing remains uncertain using long-acting gas tamponade. PATIENTS AND METHODS: Fifty consecutive eyes with idiopathic full-thickness macular holes underwent macular hole surgery with a follow up time of 6-12 months. The results of a cohort (25 eyes) with complete C3F8 (16%) vitreous fill without posturing was compared to a cohort (25 eyes) with SF6 (20%) with strict postoperative face down positioning for two weeks. RESULTS: With SF6 tamponade the anatomic success rate was 64% in the C3F8 cohort a complete closure was achieved in 88%. In the SF6 cohort, visual recovery of three lines or better was attained in 44%, resulting in a visual acuity of 20/50 or better in 12%. The mean postoperative visual acuity was 20/125 with a mean rise of 1.4 lines. In the C3F8 cohort, 72% improved for at least three lines with a mean postoperative visual acuity of 20/63 and a mean visual recovery of 3.3 lines. Visual acuity of 20/50 or better was noted in 48% of eyes. CONCLUSION: The significantly higher success rate using C3F8 tamponade without positioning compared to SF6 gas tamponade with positioning confirms the cumulative tamponade duration being a crucial factor in macular hole surgery. Using a tamponade with short-acting gas only strict postoperative positioning ensures the contact of the gas bubble with foveal tissue and gains significance with reducing bubble size. While a potential for significant visual recovery in certain cases is evident, all in all a broad variability of the postoperative success rate can be stated. In contrast, even in supine position C3F8 attains a continuous tamponade enforcing a sufficient glial wound healing without any positioning. PMID- 11210708 TI - [Acute retinal necrosis syndrome: analysis, therapy and long-term follow up of 14 eyes]. AB - PURPOSE: Acute retinal necrosis syndrome (ARN) might be complicated by retinal detachment, vasculopathy and optic neuropathy and has a poor prognosis despite intensive medical and surgical therapy. PATIENTS AND METHODS: A series of 10 consecutive patients (14 eyes) with ARN were followed for 36 months (average of 20 months +/- 10). We present the results of the clinical evaluation for diagnostic and therapeutic modalities. RESULTS: Viral etiology was confirmed in 9 of 10 aqueous-humor samples. Intraocular antibody synthesis against Varicella Zoster Virus was found in 7, against Herpes-Simplex Virus in 5 and against Cytomegalovirus in 2 samples. Three eyes had a mild clinical course with a visual acuity of 0.6 or better. Vitrectomy and silicone-oil tamponade preserved visual acuity from 0.3 to 0.1. ARN lead to blindness in 5 eyes due to vasculopathy, optic neuropathy or retinal detachment. An arterial branch occlusion was successfully overcome with i.v. heparin treatment in one patient. CONCLUSION: Aqueous-humor analysis supports clinical diagnosis. Early vitrectomy and silicone oil tamponade stabilizes retinal structure and preserves visual acuity. Occlusive vasculopathy and optic neuropathy are the main causes leading to blindness. PMID- 11210710 TI - [Peripapillary melanoma; 10-year follow-up]. AB - In early stages choroidal peripapillary choroidal melanoma may be confused with a choroidal nevus or melanocytoma. CASE REPORT: A 41-year old female was diagnosed having a choroidal nevus in close proximity to the optic nerve head. Unfortunately the patient did not show up for annual review of this lesion. Ten years after the patient was examined for the second time. A massive increase in tumor size and prominence was noted including serous retinal detachment. Medical work up excluded any metastatic growth, and the globe was enucleated. Three years later, the patient is still healthy and there are no signs of metastatic spreading. HISTOLOGICAL WORK UP: Heavily pigmented peripapillary choroidal melanoma with fascicularly vasocentric proliferative structure, but no infiltration of the sclera or the lamina cribrosa of the optic nerve. The tumor cells were of midgrade size and some of the nucleoli were slightly enlarged. Mitosis and a syncytial structure were present. Immunohistochemically S-100 proteins, HMB 45 and NSE were found. The TNM classification was: ICD-O C 69.3; pT2, G1, S0, V0, pNx, pMx, microscopically RO. CONCLUSION: Pigmented juxtapapillary tumors resembling choroidal nevi require annual surveillance. PMID- 11210711 TI - [Lipaemia retinalis due to metabolic syndrome--case report]. AB - BACKGROUND: Lipaemia retinalis is a rarely described ocular manifestation of hyperlipidemia. We report on a female patient with visual loss and visual field defects associated with lipaemia retinalis due to a metabolic syndrome. PATIENT: A 45-year-old female patient presented with bilateral slowly progressing visual loss. Additionally, there were eruptive xanthomatas all over the body. Visual acuity measured 0.2 in both eyes. There was a bilateral creamy discoloration of retinal vessels with a salmon-colored fundus. The peripheral visual field was reduced. Laboratory findings indicated a severe mixed hyperlipidemia (triglyceride 11,694 mg/dl, cholesterol 1724 mg/dl). Immediately initiated therapy to normalize the metabolism resulted in improvement of clinical symptoms. CONCLUSION: Lipaemia retinalis is an useful clinical indicator for triglyceridemia. Persistent lipaemia retinalis may lead to visual loss and visual field defects and may be a sign of severe metabolic disturbances. To prevent cardiovascular complications immediate treatment is necessary. PMID- 11210712 TI - [Langerhans-cell histiocytosis of the orbit; diagnosis, treatment and outcome in three patients -- children and adults]. AB - BACKGROUND: Langerhans cell histiocytosis usually affects children. Systemic Langerhans cell histiocytosis may be present in 37% of affected children. Ten per cent of all children die of the disease. CASE REPORTS: Patient 1. A 9-year-old boy presented with painful upper lid swelling OD. Ultrasonography revealed a space-occupying lesion adjacent to a lytic defect of the frontal bone as shown on coronal CT. MRI showed marked contrast enhancement of the mass which came close to the intracranial fossa. The vascularized tumor was excised using an anterior orbitotomy with upper lid crease incision. No evidence of local or systemic recurrence was present three years postoperatively. Patient 2. A 19-year-old male presented with foreign body sensation, double vision OS and numbness of the left face of six weeks' duration. The ocular findings revealed a sixth nerve palsy OS. Otherwise, the eyes were unremarkable. Sensitivity of cranial nerve V2 was decreased. CT revealed an osteolytic process in the lateral orbital wall and sphenoid wing. MRI demonstrated a space-occupying lesion involving the temporalis muscle laterally, the pterygopalatine fossa medially with intracranial extension into the temporal lobe. Surgical excision was performed using a transcranial approach. Signs and symptoms had completely resolved six months after surgery with no evidence of local or systemic recurrence. Patient 3. A 30-year-old male presented with right-sided headache, painful upper lid swelling and vertical diplopia. Coronal CT scan revealed a lytic defect in the frontal bone laterally. Curettage and complete excision were performed using an infrabrow incision. Follow-up examination four years later revealed an intact ocular motility with no evidence of local or systemic recurrence. In all three cases the tumor showed characteristic light-microscopy and immunohistochemical features of Langerhans cell histiocytosis. CONCLUSION: Langerhans cell histiocytosis of the orbit is an important differential diagnosis of osteolytic and/or space-occupying lesions not only in children, but also in adults. A diagnostic biopsy followed by surgical excision and/or local and systemic corticoid- and chemotherapy are essential regarding the prognosis of local and systemic disease. PMID- 11210713 TI - The effect of cocoa procyanidins on the transcription and secretion of interleukin 1 beta in peripheral blood mononuclear cells. AB - Recent data has demonstrated that cacao liquor polyphenols (procyanidins) have antioxidant activity, inhibit mRNA expression of interleukin-2 and are potent inhibitors of acute inflammation. Given the widespread ingestion of cocoa in many cultures, we investigated whether cocoa, in its isolated procyanidin fractions (monomer through decamer), would modulate synthesis of the pro-inflammatory cytokine, interleukin-1 beta. Both resting and phytohemagglutinin (PHA) stimulated peripheral blood mononuclear cells (PBMC) were investigated at the levels of transcription and protein secretion. Individual cocoa fractions were shown to augment constitutive IL-1 beta gene expression, although values varied between subjects. Interestingly, the smaller fractions of cocoa (monomer tetramer) consistently reduced IL-1 beta expression of PHA-stimulated cells by 1 15%, while the larger oligomers (pentamer-decamer) increased expression by 4-52%. These data, observed at the transcription level, were reflected in protein levels in PHA-induced PBMC. The presence or absence of PHA did not alter the effects of the cocoa procyanidins with the exception of the pentamer. This study offers additional data for the consideration of the health-benefits of dietary polyphenols from a wide variety of foods, including those benefits associated specifically with cocoa and chocolate consumption. PMID- 11210714 TI - Antioxidant actions of du-zhong (Eucommia ulmoides Oliv.) toward oxidative damage in biomolecules. AB - This study aimed to investigate the antioxidant effect of water extracts of Du zhong (WEDZ) on oxidative damage in biomolecules such as deoxyribose, DNA, and 2' deoxyguanosine (2'-dG) as induced by Fenton reaction. The WEDZ used included leaves, raw cortex, and roasted cortex. All of the WEDZ inhibited the oxidation of deoxyribose induced by Fe(3+)-EDTA/H2O2/ascorbic acid in a concentration dependent manner. At a concentration of 1.14 mg/mL, the inhibitory effect of the extracts of leaves, roasted cortex, and raw cortex was 85.2%, 68.0% and 49.3%, respectively. The extract of leaves inhibited the strand-breaking of DNA induced by the Fenton reaction at concentrations of 5 and 10 micrograms/microL. This inhibitory effect was similar to mannitol whereas the extracts of raw cortex and roasted cortex had no inhibitory effect at all. WEDZ also inhibited the oxidation of 2'-dG to 8-OH-2'-dG induced by Fe(3+)-EDTA/H2O2/ascorbic acid. Gallic acid had a prooxidant effect, but trolox and mannitol had an antioxidant effect. The leaf extract had a marked inhibitory effect on Fenton reaction induced oxidative damage in biomolecules. The extract of roasted cortex exhibited modest inhibition while the extract of raw cortex had the least inhibitory effect on oxidative damage in biomolecules. This is in contrast to gallic acid in the same reaction system, whose higher reducing power and weaker chelating ability may contribute to its prooxidant effect. In the present study, leaf extract of Du-zhong had inhibitory effect on oxidative damage in biomolecules. Therefore, drinking of Du zhong tea (leaf extract) over a long period of time may have anticancer potential. PMID- 11210715 TI - Placental leucine aminopeptidase/oxytocinase in maternal serum and placenta during normal pregnancy. AB - Placental leucine aminopeptidase (P-LAP), which is identical with cystine aminopeptidase as oxytocinase, was found to be homologous with rat insulin regulated membrane aminopeptidase (IRAP) by sequence comparison. In the current study, we determined the P-LAP levels in maternal serum and placenta during healthy pregnancy. P-LAP activities in maternal serum increased with gestation and rose to the peak of 80 IU/ml at 38 weeks of gestation. Northern blot analysis revealed the increase of P-LAP mRNA levels in placenta in the third trimester compared to the first trimester. P-LAP protein and related activities could be detected in the conditioned medium of placental tissue, while they could not be detected in that of human umbilical vein endothelial cells. Immunohistochemically P-LAP was positively stained in the apical membrane of syncytiotrophoblast cells throughout the gestation. These results established the normal range of serum and tissue P-LAP levels during pregnancy and the possible source of serum P-LAP, which will be helpful to elucidate the physiological and clinical roles of P LAP/oxytocinase/IRAP. PMID- 11210717 TI - Influence of enalapril on established pressure-overload cardiac hypertrophy in low and normal renin states in female rats. AB - To determine whether effects of angiotensin converting enzyme (ACE) inhibitors on well-established pressure overload-induced cardiac hypertrophy and coronary remodeling depend upon normal plasma renin levels, the influence of enalapril on ventricular mass and coronary vascular resistance (CVR) was determined in a low renin female rat model of chronic pressure overload, (deoxycorticosterone acetate hypertension, DOCA), and compared to its effect in a normal-renin model, (aortic construction, AC). Six weeks after experiment initiation, plasma renin activity of DOCA-treated rats was reduced to approximately 12% that of sham-treated and AC treated groups. Enalapril was then added to the drinking water of half the animals in each group for two additional weeks. Comparing experimental groups to controls, this delayed enalapril treatment had 1) no effect on the elevated arterial pressures, 2) no effect on the elevated coronary resistance, and, in the DOCA group, 3) no effect on cardiac hypertrophy. However, this brief enalapril treatment reduced absolute and relative ventricular weights of AC rats. These data suggest that circulating renin is required for the anti-hypertrophic efficacy of late-onset brief treatment with enalapril. Since enalapril-induced reversal of cardiac hypertrophy in AC rats was not accompanied by reversal of coronary remodeling, growth signals other than angiotensin II may be involved in coronary remodeling. PMID- 11210716 TI - Evidence of relaxant effect of omeprazole in rabbit corpus cavernosum in vitro. AB - The present experiments were designed to investigate the effects of omeprazole, a H(+)-K+ ATPase inhibitor, on corporal smooth muscle tone in vitro. All spontaneous contractile activity in the corpus cavernosum was blocked following omeprazole (0.1 mM-1 mM) administration. However atropine (1 microM), Nw-nitro L arginine methyl ester (L-NAME, 30 microM) or indomethacin (10 microM) did not affect the spontaneous contraction. Omeprazole (10 microM-1 mM) concentration dependently induced relaxation in corporal smooth muscle precontracted with 10 microM phenylephrine or 80 mM KCl. Pretreatment of corporal tissue with L-NAME (30 microM), indomethacin (10 microM), ammonium chloride (7.5 mM), sodium acetate (7.5 mM), tetraethyl ammonium chloride (0.5 mM) or glibenclamide (1 microM) had no effect on the omeprazole induced relaxant responses. Nimodipine, an L-type Ca++ channel blocker, relaxed corporal strips precontracted with 80 mM KCl. Collectively, these results indicate that the inhibition of spontaneous contraction and the relaxation of precontracted corporal smooth muscle by omeprazole is probably mediated by the blockade of calcium channels. Further work is needed to determine the cellular mechanism(s) of action by which omeprazole acts on corpus cavernosum smooth muscle. PMID- 11210718 TI - Hypercortisolemia does not affect the branchial osmoregulatory responses of the marine teleost Sparus sarba. AB - The effect of cortisol treatment on branchial Na(+)-K(+)-ATPase subunit mRNA abundance, enzyme activity, chloride cell number/morphometrics and serum electrolyte levels were investigated for the marine teleost Sparus sarba. Groups of fish received intraperitoneal injections of cortisol at a concentration of 4 micrograms/g body weight, daily, over a seven-day period. This dose of cortisol was sufficiently high enough to maintain a condition of hypercortisolemia as serum cortisol levels in treated fish were eleven fold higher than controls at time of sacrifice. By using branchial Na(+)-K(+)-ATPase alpha- and beta-subunit cDNA clones we were able to demonstrate that cortisol administration to S. sarba caused a significant elevation in the abundance of alpha-mRNA whereas the levels of beta-mRNA were unchanged. In addition Na(+)-K(+)-ATPase activity remained unaltered by cortisol administration. Branchial chloride cell number, exposure, apical area as well as serum Na+ and Cl- levels remained unchanged after cortisol administration. The results of this study suggest that elevated cortisol level may not necessarily translate into modulated branchial Na(+)-K(+)-ATPase activity and chloride cell function in hypo-osmoregulating marine fish. PMID- 11210719 TI - Adrenomedullin (ADM), acting through ADM(22-52)-sensitive receptors, is involved in the endotoxin-induced hypotension in rats. AB - The possible involvement of adrenomedullin (ADM) in the endotoxin-induced hypotension has been investigated in the rat. Lipopolysaccharide (LPS, 500 micrograms/kg intraperitoneum) caused a severe decrease in the blood pressure (BP), reaching maximum 2-3 h after the injection and subsiding after 12 h. The putative ADM-receptor antagonist ADM(22-52) (3 nmol/kg) counteracted LPS-induced BP lowering at 1 and 2 h, and reversed it at 3 and 6 h. CGRP(8-37), a selective antagonist of the CGRP1 receptors, was ineffective. Both ADM(22-52) and CGRP(8 37) did not evoke significant changes in the basal BP. Our findings provide strong support to the view ADM overproduction plays a major role in the LPS induced decrease in BP, and suggest a potentially important therapeutic effect of the blockade of ADM(22-52)-sensitive receptors during endotoxic shock. PMID- 11210720 TI - Supraphysiological level of estrogen exposure in vivo increases lymphoid cell death in mice. AB - Estrogen can enhance or reduce lymphocyte functions in vitro depending on dose and exposure duration. The purpose of this study was to determine the effect of in vivo 17 beta-estradiol (E2) on apoptosis and necrosis in lymphoid tissue of female C567BL/6 mice. Animals were ovariectomized (OVX), ovariectomized and 17 beta-estradiol supplemented (OVX + E2; 71 micrograms E2 per day for 14 days), sham ovariectomized (SHAM), or unhandled controls (CONTROL). Thymus and spleen were removed aseptically, cells dispersed into single cell suspensions in RPMI 1640, and measures of cell damage performed: an annexin V flow cytometric assay for markers of apoptosis and an enzyme-linked immunoassay for measures of DNA fragmentation and necrosis. OVX + E2 mice had 620 +/- 72 pg/ml 17 beta-estradiol in serum in contrast to OVX mice which had 7.6 +/- 5 pg/ml, the SHAM mice which had 2.8 +/- 1 pg/ml of serum E2, and the CONTROL mice which had 3.9 +/- 0.8 pg/ml of serum E2 (p < 0.001). There was a significantly lower percentage of viable thymocytes in OVX + E2 mice compared to the other treatment conditions (p < 0.001, respectively). There was also a significantly higher percentage of annexin V positive thymocytes in OVX + E2 mice (p < 0.005). Measures of DNA fragmentation by ELISA were higher in splenocytes from OVX + E2 mice than in the OVX, SHAM or CONTROL mice (p < 0.005). These results suggest that supraphysiological levels of estrogen in vivo induce damage in lymphoid cells; however, the impact of estrogen associated lymphoid tissue damage on specific immune functions remains to be determined. PMID- 11210721 TI - Intrathecal endomorphin-1 produces antinociceptive activities modulated by alpha 2-adrenoceptors in the rat tail flick, tail pressure and formalin tests. AB - It is known that spinal morphine produces antinociception that is modulated by alpha 2-adrenoceptors. Endomorphin-1, a newly-isolated endogenous opioid ligand, shows the greatest selectivity and affinity for the mu-opiate receptor of any endogenous substance found to date and may serve as a natural ligand for the mu opiate receptor. We examined the antinociceptive effects of endomorphin-1 administered intrathecally (i.t.) in the rat tail flick, tail pressure and formalin tests. Intrathecal endomorphin-1 produced dose-dependent antinociceptive effects in the three tests. ED50 (CI95) values for antinociception of i.t. endomorphin-1 in the tail flick test and tail pressure test were 1.9 (0.96-3.76) nmol and 1.8 (0.8-4.2) nmol, respectively. ED50 (CI95) values for phase 1 and phase 2 in the formalin test were 12.5 (7.9-19.8) nmol and 17.5 (10.2-30) nmol, respectively. Pretreatment with i.t. beta-funaltrexamine (a mu-opioid receptor selective antagonist) significantly antagonized the antinociceptive effects of endomorphin-1 in the three tests. Beta-funaltrexamine alone had not effects on the three tests. The antinociceptive effects of endomorphin-1 were also antagonized by i.t. yohimbine (an alpha 2-adrenoceptor selective antagonist). The combination of ineffective doses of i.t. clonidine (an alpha 2-adrenoceptor agonist) and endomorphin-1 produced a significant antinociception in the three tests. The results showed that intrathecal endomorphin-1 produced antinociception in a dose-dependent manner in the rat tail flick, tail pressure and formalin tests, which was mediated by spinal mu-opioid receptors and modulated by alpha 2 adrenoceptors. PMID- 11210722 TI - Systemic administration of d-amphetamine induces long-lasting oxidative stress in the rat striatum. AB - The long-term effect of d-amphetamine (AMPH) on the induction of oxidative stress was examined in vivo in the rat brain. In this study, 2,3-dihydroxybenzoic acid (2,3-DHBA) and malonaldehyde (MDA) were used as the index of the hydroxyl radical and lipid peroxidation, respectively. The levels of 2,3-DHBA, MDA and dopamine (DA) in striatal homogenates were examined 7 days following injection of a single large dose of AMPH (7.5 mg/kg, i.p.) in rats pretreated with desipramine (10 mg/kg, i.p.), an agent that inhibits the metabolism of AMPH. Our results showed that 2,3-DHBA and MDA levels were significantly increased by AMPH, whereas DA and its metabolites, DOPAC and HVA were depleted in the striatum. Pretreatment with the glutamate NMDA receptor subtype antagonist MK-801 (1 mg/kg, i.p.) attenuated the increases of 2,3-DHBA and MDA, and provided partial protection against the long-lasting loss of DA produced by AMPH. Overall, the results demonstrate that AMPH could induce sustained production of free radical and oxidative damage, and lead to DA terminal degeneration in the striatum of the rat. PMID- 11210723 TI - Role of capsaicin sensory nerves and EGF in the healing of gastric ulcer in rats. AB - Accumulating evidence indicates that capsaicin sensitive afferent fibers play a pivotal role not only in gastroprotection but also in ulcer healing. Denervation of capsaicin sensitive afferent fibers exerts an adverse action on these effects. However, whether such an action is mediated through a depression on epidermal growth factor (EGF) is undefined. In this study, the effects of denervation of sensory neurons with capsaicin (100 mg/kg, s.c.) on acetic acid-induced chronic gastric ulcers and their relationship with the EGF expression in salivary glands, serum and gastric mucosa were investigated. Capsaicin significantly increased ulcer size, decreased gastric mucosal cell proliferation at the ulcer margin, angiogenesis in the granulation tissue and also gastric mucus content. Ulcer induction by itself dramatically elevated EGF levels in salivary glands and serum on day 1 and 4, and also in the gastric mucosa on day 4. However, capsaicin completely abolished these effects. It is concluded that stimulation of EGF expression in salivary glands and serum may be one of the mechanisms by which capsaicin sensitive nerves contribute to the gastroprotective and ulcer healing actions in the stomach. PMID- 11210725 TI - [The future trend of life science researches in Japan]. PMID- 11210724 TI - Acetyl-seryl-aspartyl-lysyl-proline is a novel natural cell cycle regulator of renal cells. AB - A natural tetrapeptide, acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is a physiological negative regulator of hematopoiesis. The precursor of AcSDKP, thymocin beta 4, is expressed in many tissues including kidney. The present study examined the antiproliferative effect of AcSDKP in two renal cell lines, namely, renal interstitial fibloblasts cell line (NRK 49F) and renal proximal tubular epitherial cells (LLC-PK1). An addition of AcSDKP for 48 hours in theses cells resulted in a concentration-dependent attenuation in the proliferation rate (significant difference to non-treated cells was observed at 10(-9) to 10(-5) M AcSDKP) determined by a colorimetry of alamer blue oxidation. The cell cycle analysis of NRK 49F cells treated with AcSDKP showed that AcSDKP significantly reduced the ratio of S-phase to G2/M-phases. Thus, physiological concentrations of AcSDKP is capable of altering cell cycle to inhibit the proliferation of renal cells. PMID- 11210726 TI - [Vasculitis--changes of the concept and the relation to ANCA]. PMID- 11210727 TI - Insights into the pathogenesis of rheumatoid arthritis from application of anti TNF therapy. PMID- 11210728 TI - Haemopoetic stem cell transplantation in autoimmune diseases, with special reference to rheumatoid arthritis. PMID- 11210729 TI - [Molecular mechanisms governing autoantibody production in patients with SLE]. PMID- 11210730 TI - [Signal pathways in immune systems: IL-1 R/Toll-like receptor family]. PMID- 11210731 TI - [Action of transforming growth factor-beta and diseases]. PMID- 11210732 TI - [Clinical applications and limitations for use of immunosuppressive drugs in inflammatory connective tissue diseases]. PMID- 11210733 TI - [Current status and problems in human gene therapy]. PMID- 11210734 TI - [Treatment strategy of pediatric rheumatic diseases: up-date]. PMID- 11210735 TI - [Autophagy and apoptosis]. PMID- 11210736 TI - [Intercellular adhesion molecule-1 (ICAM-1) mediated gene delivery to rheumatoid synovial cells using the Fab fragments of anti-ICAM-1 monoclonal antibody]. PMID- 11210737 TI - [Antigen-specific T cells transduced with interleukin-10 ameliorate experimentally induced arthritis without impairing the systemic immune response to the antigen]. AB - For the treatment of rheumatoid arthritis, efficient drug delivery methods to the inflamed joints need to be developed. Since T cells expressing an appropriate autoantigen-specific receptor can migrate to inflamed lesions, it has been reasoned that they can be employed to deliver therapeutic agents. In order to examine the ability and efficiency of such T cells as a vehicle, we employed an experimentally induced model of arthritis. Splenic T cells from DO 11.10 T cell receptor transgenic mice specific for OVA were transduced with murine IL-10. Adoptive transfer of the IL-10-transduced DO 11.10 splenocytes ameliorated OVA induced arthritis, in spite of the presence of around 95% non-transduced cells. Using GFP as a marker for selection, the number of transferred cells needed to ameliorate the disease was able to be reduced to 10(4). Preferential accumulation of the transferred T cells was observed in the inflamed joint, and the improvement in the disease was not accompanied by impairment of the systemic immune response to the antigen, suggesting that the transferred T cells exert their antiinflammatory task locally, mainly in the joints where the antigen exists. In addition, IL-10-transduced DO 11.10 T cells ameriolated mBSA-induced arthritis when the arthritic joint was co-injected with OVA in addition to mBSA. These results suggest that T cells specific for a joint specific antigen would be useful as a therapeutic vehicle in rheumatoid arthritis for which the arthritic autoantigen is still unknown. PMID- 11210738 TI - [Treatment of murine collagen-induced arthritis by ex-vivo EC-SOD gene transfer]. PMID- 11210739 TI - [Gene therapy for rheumatoid arthritis by apoptosis-related gene transfer]. PMID- 11210740 TI - [Amelioration of adjuvant arthritis by gene therapy suppressing Src activity]. PMID- 11210741 TI - Treatment of arthritis with cyclin-dependent kinase inhibitor gene. PMID- 11210742 TI - [Identification and characterization of pathogenic autoreactive T cells in patients with idiopathic thrombocytopenic purpura]. PMID- 11210743 TI - [Diversity and cross-recognition of self-reactive T cells in primary biliary cirrhosis]. PMID- 11210745 TI - [Allergen-peptide immunotherapy against Japanese cedar pollinosis]. PMID- 11210744 TI - [Molecular mechanism of cancer-associated retinopathy and tumor antigens]. PMID- 11210746 TI - [Identification of peptide superagonists using combinatorial chemistry and mass spectrometry]. PMID- 11210747 TI - [NALT immune system for the development of AIDS mucosal vaccine]. PMID- 11210748 TI - [Efficient replication of human immunodeficiency virus type 1 in cytokine induced CD 4+ T helper 1 (Th 1)- and Th 2-type conditions]. AB - Potent stimuli for CD 4+ T cell differentiation are cytokines. Among them, IL-12 or IL-4 induce naive CD 4+ T cells to Th 1 or Th 2 cells, respectively. In this study we found that macrophage-tropic (M-tropic) HIV-1 strains more efficiently replicated in interleukin 12 (IL-12) induced T helper 1 (Th 1)-type culture derived from normal CD 4+ T cells than T-cell-line-tropic (T-tropic) strains did. In contrast, T-tropic strains preferentially infected IL-4 induced Th 2-type culture derived from same donor CD 4+ T cells. Additional studies using chimeric viruses demonstrated that the V 3 region of gp 120 was the principle determinant for this efficient replication. It was also isolated T-tropic viruses from an acutely infected patient who had been evidenced as severe CD 4 depletion during short time course. These results indicate that HIV-1 isolates exhibit differences in the ability to infect CD 4+ T cell subset such as Th 1 or Th 2 cells, and that this difference may partly correlate with the viral pathogenesis. The findings suggest that immunological condition is one of the factors responsible for inducing selection of HIV-1 strains. PMID- 11210749 TI - [Crosstalking between HIV and HHV-8 via IL-6 in AIDS]. PMID- 11210750 TI - [Role of chemokine in HIV infection]. PMID- 11210751 TI - [HIV-1: entry inhibitors and skin immunization]. PMID- 11210752 TI - [Cytokine and fibrotic diseases in the skin]. PMID- 11210753 TI - [Role of cytokine in renal fibrosis]. PMID- 11210755 TI - [Cytokines and liver fibrosis]. PMID- 11210754 TI - [The role of IL-18 on the pathogenesis of Crohn's disease]. PMID- 11210756 TI - Cytokine and atherosclerosis: a possible role of osteopontin in development in diabetic macroangiopathy. PMID- 11210757 TI - [Organ transplantation and oral tolerance]. PMID- 11210758 TI - [Characterization of humoral immunosuppressive factors induced after allogeneic blood transfusion and their application for organ transplantation]. PMID- 11210759 TI - [Clinical impact of lymphocyte sensitivity to immunosuppressants]. PMID- 11210760 TI - [Immunosuppression in living donor liver transplantation from ABO blood type incompatible donors]. PMID- 11210761 TI - [MCTD and pulmonary hypertension]. PMID- 11210762 TI - [Meningitis in mixed connective tissue disease]. PMID- 11210763 TI - [Treatment of membranous lupus nephritis]. PMID- 11210764 TI - [Scleroderma renal crisis (SRC): hypertensive, normotensive]. PMID- 11210765 TI - [MPO-ANCA related angiitis]. PMID- 11210766 TI - [Central nervous system involvement in systemic lupus erythematosus]. PMID- 11210767 TI - [Hemophagocytic syndrome]. PMID- 11210768 TI - [Antiphospholipid syndrome and renal diseases: a report of two cases]. PMID- 11210769 TI - [COX-2--what are the clinical implications?]. PMID- 11210770 TI - [Innovation in COX-2 technology]. PMID- 11210771 TI - [Education of rheumatology for medical students]. PMID- 11210772 TI - [Clinical significance of magnetic resonance imaging of skeletal muscles in idiopathic inflammatory myopathies of adults]. AB - The purpose of this study was to evaluate the clinical significance of magnetic resonance imaging (MRI) of skeletal muscles in Japanese patients with idiopathic inflammatory myopathies (IIM). MRI was performed in 23 adult patients with IIM, including 10 with polymyositis, 12 with dermatomyositis, and 1 with focal myositis. Seven (73%) of 11 patients with active IIM and 2 (17%) of 12 patients with inactive IIM showed hyperintensity of T 2-weighted images and normal intensity of T 1-weighted images, indicating "edema-like abnormalities" (MRI findings for active myositis). Muscle lipomatosis and fibrosis were demonstrated in four patients and 1 patient, respectively. Considerable selectivity of muscles in developing inflammatory disorders was found. In quadriceps muscles, for example, vastus muscles seemed to be more often affected in DM patients, whereas adductors were more often affected in PM patients. Serial examination of muscle MRIs was carried out in 4 patients and the findings paralleled the disease activities. The muscle MRI findings did not necessarily correlate with other findings, such as the presence of muscle weakness, elevated serum creatine kinase levels, myogenic electromyogram, or muscle biopsy findings. The muscle MRI was considered to be an additional useful tool for the diagnosis, evaluation of disease activity, and planning treatment of IIM. PMID- 11210773 TI - [Radiological evaluation of foot deformities in rheumatoid arthritis]. AB - Deformities of the feet are common in patients with rheumatoid arthritis (RA). We investigated whether there was any correlation among forefoot deformities, flat foot or articular destruction of the midfoot and hindfoot, in 146 feet of 73 RA patients whose age varied from 26 to 81 years (mean 58.5 years). In all patients, anteroposterior (AP) and lateral radiographs of the feet with weight bearing were obtained. The hallux valgus angle (HVA), the intermetatarsal angle between the 1st and 2nd metatarsals (M 1 M 2), and the intermetatarsal angle between the 1st and 5th metatarsals (M 1 M 5) were measured on AP radiographs. On slateral radiographs, the height of the arch was measured and articular destruction of the talocalcaneal, talocrural, talonavicular, cuneonavicular and cuneometatarsal joints was measured and classified using Steinbrocker's classification. The average HVA was 23.4 degrees, the average M 1 M 2 was 11.1 degrees, and the average M 1 M 5 was 28.4 degrees. There was no correlation between forefoot deformities and flat foot. There were significant correlations between arthritic destruction of the cuneometatarsal joint and HVA, M 1 M 2 and M 1 M 5. The correlations between arthritic destruction of the cuneonavicular joint and HVA or M 1 M 2 were also significant, although weaker. Thas, we found some relationships between forefoot deformity and arthritics destruction of midfoot joints. Especially, the correlations between arthritic destruction of the cuneonavicular and cuneometatarsal joints and forefoot deformities were significant. Many radiographic methods for the assessment of RA have been reported, however, it is difficult to assess sarthritic destruction of rheumatoid feet with the existing methods. Accordingly, a new method should be established. PMID- 11210774 TI - [Autoimmune cholangitis (AIC) associated with myositis in monozygotic twins]. AB - A 53-year-old female suffered from joint pain and muscle weakness in all extremities in 1991. Laboratory data showed increased creatine phosphokinase (CK) and aldolase. Liver dysfunction and weakness of proximal muscles also appeared and polymyositis (PM) was suspected. Two years later, she was diagnosed with dermatomyositis (DM) through skin and muscle biopsy. Because elevation of biliary enzymes and transaminases were continued, liver biopsy was performed in 1997. Histopathological findings of her liver were compatible with primary biliary cirrhosis (PBC). Similar conditions were noticed in her identical twin as well. DM associated with PBC is unusual and cases of monozygotic twins with both conditions are very rare. The difference between PBC and autoimmune cholangitis (AIC) which has recently reported and the genetic influence on the pathogenesis of DM and AIC are also discussed. PMID- 11210775 TI - [Polyarthralgia as the initial manifestation of isolated ACTH deficiency]. AB - A 57-year-old man, employed as a taxi driver, noticed arthralgia of his fingers beginning in May 1999. He was unable to work due to the arthralgia and the accompanying general malaise and anorexia, and was thus admitted to a local hospital in July 1999. Since a diagnosis of rheumatic disease was suspected due to elevated inflammatory reactions and joint symptoms, he was referred to our hospital in September 1999. Although no joint swelling was observed, severe tenderness was present in both the fingers and wrists. His grasping power had decreased markedly and fever was intermittently observed. All autoantibodies aside from antinuclear antibody were negative. Given that hyponatremia (126 mEq/l) and fasting hypoglycemia were demonstrated, an endocrinological examination, in particular for hypopituitary-adrenal function, was performed. Both plasma and urinary cortisol concentrations were very low, and an associated low concentration of plasma ACTH (6.0 pg/ml) was noted. The ACTH circadian rhythm was absent and there was no response to the administration of corticotropin releasing hormone. All other pituitary hormones were secreted at normal levels and brain MRI revealed a normal appearance of a pituitary gland. Based on these findings, the patient was diagnosed as having isolated ACTH deficiency. Arthralgia and general malaise both improved soon after replacement of glucocorticoid, and CRP levels were normalized. Isolated ACTH deficiency should be considered in the differential diagnosis of patients suffering from polyarthralgia, given that fever and increased inflammatory reactions occasionally develop and that rheumatic symptoms are also present, as in the present case. PMID- 11210776 TI - [Two cases of acute lupus peritonitis]. AB - We report two cases of systemic lupus erythematosus (SLE) diagnosed when acute peritonitis was appeared. Case 1 was a 20 year-old woman suffering from stomachache and right lower abdominal pain. Case 2 was a 40 year-old woman with diarrhea, epigastralgia, pollakisuria. In both cases, their peritoneal fluids were exudative with positive autoantibodies. After high dose steroid therapy, abdominal symptoms and ascites improved promptly. However, due to the complication of lupus nephritis, additional therapy was necessary. To characterize the feature of lupus peritonitis (LP), we examined the clinical and laboratory findings of LP from the literature. In patients with acute LP, abdominal pain, vomiting, diarrhea were significantly more common compared with chronic LP patients (P < 0.05), and fever, arthritis, central nervous system involvement and cystitis were more common. In patients with chronic LP, pleural effusion and pericardial effusion were more common compared with acute LP patients. Gastrointestinal manifestations such as abdominal pain, vomiting and diarrhea were more common in patients with acute LP compared with patients with chronic LP. Most patients with chronic LP were asymptomatic, ascites and serositis being the only clinical findings. The response to steroid therapy was better in acute LP. PMID- 11210777 TI - [Susceptibility genes in rheumatoid arthritis]. PMID- 11210778 TI - [Current concepts of joint replacement]. PMID- 11210779 TI - An autopsy case of accidental asphyxiation in a storage room for apples. AB - A 12-year-old boy died in a storage room and his mother was rescued from the same storage room, where many apples were being stored. The atmosphere in the room was strictly controlled and the concentration of oxygen (O2) was recorded. The cause of death was suffocation. According to the records, the concentration of O2 was about 2.7% when the boy died. On the other hand, it was about 3.4% when his mother entered the room and she survived, although she remained unconscious for about four hours. These findings show that the absolute concentration of O2 causing acute death due to O2 deficiency is approximately 2.5-3.0%. PMID- 11210780 TI - [Advances in perimetry]. PMID- 11210781 TI - [Assessment of visual function before and after macular surgery by pattern visual evoked cortical potentials]. AB - PURPOSE: To investigate pre- and postoperative visual function in patients with macular hole and those with epiretinal macular membrane (ERM) by means of visual evoked cortical potential (VECP). MATERIAL AND METHODS: VECP was recorded from 15 eyes with macular hole and 9 eyes with ERM prior to and 3 months after surgical treatment. Check sizes of 30' for transient stimulation, and 7.5', 15', 30', 60' and 120' for steady-state stimulation were applied. RESULTS: In transient VECPs, the P 100 component was prolonged and attenuated in both diseases before surgery, and it remained unchanged after surgery. In the eyes with macular hole, the amplitudes of steady-state VECPs showed significant reduction in 15' and 30' check sizes before surgery, and recovered only in 15' check size after surgery. The preoperative spatial frequency curve of ERM was lowered in the whole frequency range measured. CONCLUSIONS: VECP reflected the area of macular hole and ERM. VECP changes after surgery were considered to depend on the degree of surgical invasion. PMID- 11210782 TI - [Usefulness of frequency doubling technology as a screening test for glaucoma]. AB - PURPOSE: To evaluate the usefulness of frequency doubling technology (FDT) as a screening test. MATERIAL AND METHODS: One-hundred and six eyes of 106 patients with primary open-angle glaucoma and 66 eyes of 66 normal subjects were examined in a screening program using FDT. The test results were evaluated by comparison with the results obtained by Humphrey Field Analyzer (HFA) and/or the appearance of the optic disk. RESULTS: The sensitivity and specificity of FDT regarding the existence of abnormal points worse than mild relative loss were 88% and 95%, respectively. At least one abnormal point worse than mild relative loss in FDT was detected in over 90% of the abnormal hemifields equal to or worse than stage 2 of Aulhorn's classification modified by Greve, but it was 55% and 65% in stages 0-1 and 1, respectively. Nerve fiber layer defects were found in 67% of the hemifields, which was judged as abnormal in FDT but normal in HFA. CONCLUSION: FDT is useful for detection of glaucomatous visual field defects in stage 2 or worse. FDT may detect early glaucomatous visual field defects overlooked in HFA testing. PMID- 11210783 TI - [Two cases of digitalis toxicity with reversible and severe decrease of visual acuity]. AB - BACKGROUND: We performed electrophysiologic tests on two patients with digitalis toxicity who first had photophobia and xanthopsia and revealed reversible reduced visual acuity and binocular central scotoma. CASES: The patients were a 72-year old male and a 54-year-old male who had symptoms of digitalis toxicity. FINDINGS: The corrected visual acuity was severely decreased during digitalis toxicity, 0.02 oculus dexter (OD) and 0.1 oculus sinister (OS) in case 1 and 0.04 OD and 0.2 OS in case 2. But visual acuity recovered as the blood levels of digitalis decreased to the normal level and the corrected visual acuity was 0.7 OD and 0.8 OS in case 1 and 0.8 OD and 0.9 OS in case 2. We recorded 30 Hz-flicker electroretinogram (ERG), single flash ERG, photopic ERG, and scotopic ERG when digitalis blood levels were elevated and normal. Decreased amplitudes of 30 Hz flicker ERG and photopic ERG suggested that photoreceptor function was disturbed at digitalis toxicity and cone dysfunction was more severely disturbed than rod dysfunction. CONCLUSION: 30 Hz-flicker ERG, as well as electrocardiogram and digitalis blood level, is a relatively convenient and useful measure of digitalis toxicity. It is necessary consiler toxicity when severe visual dysfunction is observed in patients with digitalis therapy. PMID- 11210784 TI - [Development of corneal storage medium--first report. Examination of rabbit cornea]. AB - PURPOSE: To develop and evaluate a new corneal storage medium with a simple formula by histological methods. METHODS: We compared two corneal storage media, containing minimum essential medium (MEM) and 2.5% chondroitin sulfate, pH 7.33 and osmolality of 320 mOsm/kg, to OPTISOL-GS. The differences in the two media were the molecular weight (MW) and source of chondroitin sulfate. MW of Medium I was 27,500 and MW of Medium II was 33,700. A cornea with scleral rim obtained from a Japanese white rabbit was stored in either Medium I or Medium II and the fellow cornea was stored in OPTISOL-GS for 7 or 14 days at 4 degrees C. Histological examination of corneal endothelial cells was performed both by scanning electron microscopy and by transmission electron microscopy. RESULTS: At day 7, there was no significant difference in histological findings among the rabbit corneas stored in OPTISOL-GS, Medium I, or Medium II. At day 14, corneas stored in OPTISOL-GS or Medium I showed similar histological findings. In Medium II, endothelial cells showed marked degeneration. CONCLUSION: The results of experiments with rabbit cornea indicated that OPTISOL-GS and Medium I could preserve endothelial cellular structure better than Medium II. The difference between Medium I and Medium II was only the MW of the chondroitin sulfate used. The MW may be an important factor to determine suitable chondroitin sulfate for developing a corneal storage medium. PMID- 11210785 TI - [Usefulness of routine ophthalmologic examination for cytomegalovirus retinitis in acquired immunodeficiency syndrome patients]. AB - PURPOSE: To evaluate the usefulness of routine ophthalmologic examinations for cytomegalovirus retinitis in acquired immunodeficiency syndrome (AIDS) patients. METHODS: Clinical symptoms of cytomegalovirus (CMV) retinitis in patients with AIDS who had circulating CD4+ T lymphocytes 50/microliter or less and received monthly ophthalmological examinations (examined group) were compared with those of the patients detected by non-routine ophthalmological examinations (unexamined group). RESULTS: The patients in whom early CMV retinitis was detected by monthly ophthalmological examinations had no subjective symptoms or iritis. The size of CMV retinitis was smaller than 2 disc diameters and it did not extend to the papillomacular area in a majority of the patients. On the other hand, the size of CMV retinitis in the unexamined group was larger than 10 disc diameters and it extended to the papillomacular area in most cases. The visual prognosis of the examined group was better than that of the unexamined group. CONCLUSIONS: To protect visual acuity, it is important to conduct monthly ophthalmological examinations in patients with AIDS whose serum CD4+ T lymphocyte counts are 50 cells/microliter or less. PMID- 11210786 TI - [Prognosis of endogenous fungal endophthalmitis and utility of Ishibashi's classification]. AB - PURPOSE: Prognostic evaluations of eyes with endogenous fungal endophthalmitis were made according to the classification proposed by Ishibashi. PATIENTS AND METHODS: We surveyed endogenous fungal endophthalmitis cases at four Nihon University Hospitals and 20 branch hospitals. Sixty eyes of 34 patients were classified into five stages according to Ishibashi's proposal, and therapeutic methods and visual prognosis in each stage were then evaluated. RESULTS: Systemic antifungal drugs were efficacious in 82% of stage II and 69% of stage IIIa cases. Even among stage III b cases, antifungal drugs were efficacious in 42%. Among the unresponsive cases, only half had been given the maximum dosage of antifungal drugs. Half of the eyes in which vitrectomy was performed at stage III b achieved a postoperative visual acuity of 0.5 or better and none had a visual acuity of less than 0.03. CONCLUSION: Based on the above results, we concluded that systemic antifungal drugs should be administered at the maximum dosage in stage II and III a cases. If these eyes progress to stage III b despite the maximum dosage, vitrectomy is indicated. For stage III b eyes, the maximum dosage should be administered first. If the maximum dosage is not efficacious, vitrectomy should be carried out before progression to stage IV. PMID- 11210787 TI - [A case of malignant myoepithelioma in the lacrimal gland]. AB - BACKGROUND: A case of malignant myoepithelioma in the lacrimal gland is reported. CASE: The patient, a 77-year-old male with increasing proptosis in the left eye was referred to us. Steroid therapy was not effective, therefore lateral orbitotomy was performed. RESULT: On pathological examination, the proper structure of actini was normal, but the cord of actini revealed the destruction layer tapering into the surrounding area. The tumor was composed of sarcomatoid changes with spindle-shaped cells, collagen fibers, and myxoid pattern. immunohistochemically, tumor cells were positive for epithelial membrane antigen (EMA) and alpha-smooth muscle actin (alpha-SMA). Electronmicroscopy showed desmosomes in intercellular junctions. CONCLUSION: Recently, there have been attempts to distinguish myoepithelioma from pleomorphic adenoma on the basis of cellular organization. In our case, duct formation was less than in pleomorphic adenoma. Therefore we diagnosed this tumor as malignant myoepithelioma. PMID- 11210788 TI - [A case of central retinal vein occlusion followed by branch retinal artery occlusion]. AB - BACKGROUND: The influence of retinal artery circulation on central retinal vein occlusion (CRVO) is not well known. CASE: A 73-year-old man with hypertension complained of transient visual loss in his left eye. At initial examination, ophthalmoscopy of his left eye showed mild dilatation and tortuosity of the retinal vein and a few dot hemorrhages. Fluorescein angiography disclosed normal arm-to-retina circulation time and no leakage of dye, but delayed retinal circulation time. These findings indicated venous stasis retinopathy of CRVO. In spite of intravenous infusion of prostaglandin E1 and vasodilative treatment, four days after initial examination, the patient's left eyeground showed complication of branch retinal artery occlusion (BRAO). A fibrinolytic agent was given intravenously, but four weeks later, his left eyeground developed typical hemorrhagic retinopathy. The hemodynamics of retrobulbar arterial circulation were investigated by color Doppler imaging. CONCLUSION: We report a case of venous stasis retinopathy of CRVO associated with BRAO, that developed hemorrhagic retinopathy despite treatment with prostaglandin E1 and other vasodilative agents. We think that arterial insufficiency might be responsible for the conversion from venous stasis retinopathy to hemorrhagic retinopathy of CRVO. PMID- 11210789 TI - [A case of malignant melanoma occurring 63 years after evisceration]. AB - BACKGROUND: We report a rare case of a 69-year-old woman with malignant melanoma of her right socket, who had undergone evisceration of her right globe for unknown reasons at the age of 6. CASE: A 69-year-old woman presented with the complaint of inability to keep the prosthesis in her socket. A large blackish brown mass was seen behind the eyelids, and biopsy of this tissue revealed a mixed type malignant melanoma. A right exenteration was performed and histopathologic examination demonstrated a large tumor mass anterior and adjacent to the remains of the eviscerated globe. CONCLUSION: During evisceration, uveal pigment may be incompletely removed from the globe, or may be inadvertently scattered in the orbit. This case may demonstrate the development of a malignant melanoma from the uvea of an eviscerated globe. We recommend that careful long term follow-up be performed on patients who have undergone evisceration. PMID- 11210790 TI - [Bioethics in educational examinations and patient treatment]. PMID- 11210791 TI - [Ethics in transplantation]. PMID- 11210792 TI - [Socio-economic and ethical aspects of ambulatory treatment for neoplasms in Germany]. PMID- 11210793 TI - [Legal aspects of European ethical conventions]. PMID- 11210794 TI - [Legal basis for execution of clinical protocols]. PMID- 11210795 TI - [Philosophical basis of bioethics]. PMID- 11210796 TI - [Ethical aspects of gene therapy]. PMID- 11210797 TI - [Ethical aspects of clinical probes for diagnosing neoplasms from the pathologists' point of view]. PMID- 11210798 TI - [Ethical aspects of examining patients without access to legal representation- history and current situation in Germany]. PMID- 11210799 TI - [Awareness of responsibility by German physicians in the last 50 years]. PMID- 11210800 TI - [Reciprocal relationships among ethics, politics and economics in medicine based on studies from the German Health Service]. PMID- 11210801 TI - [Interpretation of medical investigation results]. PMID- 11210802 TI - Basic research for cardiovascular reconstruction, organ transplantation and organ protection under the limits of German animal protection law. PMID- 11210803 TI - Sixth of November of 1939. Collegium Novum hall 56 "Sonderaktion Krakau". PMID- 11210804 TI - Bioethics, rooted in "Weltethos" or in Christian culture? PMID- 11210806 TI - [Education of medical students in the field of bioethics--agreement with newly sanctioned programs of study]. PMID- 11210805 TI - [Ministerial care and palliative medicine. Multiple types of care for people suffering from neoplasms based on the SUPPORT Project]. PMID- 11210807 TI - [The significance of ethics in medical education]. PMID- 11210808 TI - [Psycho-oncologic care--interdisciplinary problem. Herfordzki's model]. PMID- 11210809 TI - [Ethics in medicine from an interdisciplinary perspective]. PMID- 11210810 TI - [Procedures regarding dying patients. Experience with ethical consultations]. PMID- 11210811 TI - [Ethical aspects of treatment interruption]. PMID- 11210812 TI - [German legislation regarding organ transplantation]. PMID- 11210813 TI - [Ethical aspects of organ transplantation]. PMID- 11210814 TI - [The Croatian Society for Infant, Child and Adolescent Psychiatry: present state and proposals for improving the development of child and adolescent psychiatric services in Croatia]. AB - The paper presents the current state of child and adolescent psychiatry in the Republic of Croatia. Thirty-seven psychiatrists practicing child and adolescent psychiatry in the entire Republic point to the lack of staff in this subspecialty profession. The subspecialty was approved by the Ministry of Health in 1994. The city of Zagreb satisfies the criteria of some European countries as regards the number of staff, but not as regards the organization of the service for child and adolescent psychiatry (e.g. lack of university hospital department as the base for medical teaching and further specialist training). In other and larger centers in the Republic the situation is well below the criteria achieved in this profession, particularly in the countries of the European Union and the USA. Still, psychiatric services in some towns tend to support the development of child and adolescent psychiatry in their environment by providing facilities and staff. There are still attempts, even in the health service itself, to overcome this lack of personnel and organization by transferring numerous cases from the domain of child and adolescent psychiatry to experts in other medical specialties or non-medical professionals, instead of improving the development of child and adolescent psychiatry. In some countries of the European Union and the USA it has already reached the monospecialty status, a tendency supported by the UEMS, which also makes efforts to coordinate programs of specialist training in the European countries. The described situation certainly has consequences in the of mental health care of children, adolescents and their families, because their treatment often begins only when a disorder has visibly developed. Its clinical manifestations can take very different forms. PMID- 11210815 TI - [Lyme borreliosis in Croatia from 1987 to 1998--epidemiologic aspects]. AB - Lyme borreliosis is one of the most common diseases originating from natural foci in the Republic of Croatia. Some 200 cases are reported every year to the Epidemiological Department of Croatian National Institute of Public Health, but data from hospital treatment and individual limited research show that the number of infected is certainly higher. Officially reported cases have been used and analysed in this article. Although, aware of the limits of such a source, the results gained with this analysis point to certain epidemiological characteristics of Lyme borreliosis in Croatia, which can be useful. Clinical manifestations might vary, depending on the part of the world, i.e. type of Borrelia involved. In Croatia, skin manifestations are predominant--erythema (chronicum) migrans. The disease generally does not occur in Southern Croatia; it has been only sporadically reported in the area south of Zadar. Although the tick, the vector of this disease, can be found everywhere in Croatia, data about vector species and their presence in the coastal area are not complete or they are missing. Therefore, additional entomological, epidemiological, and clinical research are necessary to clarify the absence of Lyme borreliosis in Southern Croatia. PMID- 11210816 TI - [Characteristics of SHV-2 beta-lactamase from 2 hospitals in Zagreb]. AB - The aim of the investigation was to determine the properties of SHV-2 type of beta-lactamase from two hospitals in Zagreb. The production of SHV-2 beta lactamase was determined in 22 clinical isolates of K. pneumoniae by isoelectric focusing, PCR and PCR/Nhe test. The organisms were collected from the Sestre Milosrdnice Hospital and Dubrava Hospital in Zagreb during 1994-1995. Nine out of 22 strains transferred resistance to E. coli recipient. In spite of the fact that SHV-2 beta-lactamase is a cefotaximase, only 18% of the strains were resistant to cefotaxime with standard inoculum size but the percentage of resistant strains rose to 39% when the inoculum size was increased to 10(7) CFU/ml. The frequency of transfer was lower when more stringent conditions were applied (higher concentration of cefotaxime in the medium) but the transconjugants obtained with such conditions, displayed higher level of resistance to third generation cephalosporins. The genes responsible for resistance to aminoglycosides were usually transferred on the same plasmid with the genes encoding ESBLs. All strains produced an enzyme with the isoelectric point of 7.6, yielded an amplicon with SHV specific primers and had positive PCR/Nhe test. PMID- 11210817 TI - [In situ PCR in the diagnosis of acute leukemia]. AB - Cytomorphologic and cytochemical bone marrow analysis is essential in the diagnosis of acute leukemia. Immunophenotyping and conventional cytogenetics, just as fluorescent in situ hybridization (FISH) are other diagnostic procedures, as well as genome analysis by PCR (polymerase chain reaction). PCR is inevitable in searching for minimal residual disease, because it may detect very small amount of malignant hematopoietic cells even when a patient is in complete remission (less than 5% malignant cells in bone marrow and disappearance from peripheral blood) which helps better monitoring of patients. By in situ hybridization (ISH) it is possible to associate specific cell type with genome alteration, but the method is not sensitive enough. By combining ISH and PCR a novel technique with increased sensitivity was developed, PCR in situ, which enables nucleic acid amplification in an intact cell. In this case report we present two patients whose bone marrow aspirates were analyzed also by PCR in situ. PMID- 11210818 TI - [Treatment of pseudarthroses of the olecranon with the anatomical hook plate]. AB - We report the results in seven patients treated surgically for nonunion of the olecranon. Four nonunions occurred after primary treatment with tension band wiring and three nonunions occurred after open reduction internal fixation with plates and screws or lag screws only. All patients were treated with cancellous bone grafting and open reduction internal fixation using anatomical hook plates. All nonunions united within 6 months after the treatment. In all patients the range of motion of the elbow improved significantly. PMID- 11210820 TI - [The role of iron in neoplasms]. AB - The purpose of this review is to concisely summarize the current knowledge of iron participation in the carcinogenic process, especially from the standpoint of redox regulation, and to introduce a hypothesis for the mechanism. In both animals and humans, primary neoplasms develop more frequently at body sites of excessive iron deposits. Iron exerts its carcinogenic effects by catalysing formation of hydroxil radicals, suppressing activity of host defence cells and promoting cancer cell multiplication. Manipulations of cellular iron metabolism for modulating normal and malignant cell proliferation is described. Quantitative evaluation of body iron and iron-withholding proteins has prognostic value in cancer patients. Procedures associated with lowering host iron intake and inducing host cell iron efflux can assist in prevention and management of neoplastic disease. PMID- 11210819 TI - [Corrective osteotomy in the treatment of degenerative changes in the knee joint]. AB - Angular deformity of the knee can be corrected by high tibial osteotomy or distal femoral osteotomy. In this research we have analysed effects of corrective osteotomy in knees with varus or valgus deformity. In this research we present a long-term evaluation of 67 patients older than 40 with angular deformity of the knee in which high tibial osteotomy and distal femoral osteotomy were performed at the Department of Orthopaedic Surgery, School of Medicine, University of Zagreb, in the period 1982-1992. Operation was performed bilaterally in 14 patients. There were 66 knees with varus deformity and 15 with valgus deformity out of a total of 81 knees. The most patients with valgus deformity were corrected by supracondylar osteotomy and the most with varus deformity by osteotomy of proximal tibia. The average preoperative duration of symptoms was 6.1 years. The average age was 57.5 at the moment of operation. The mean follow up was 7 years (range 3-13 years). We assessed the degree of arthrosis according to Ahlbock in five-grade scale. The mean arthrosis was 2.0 preoperatively, 2.2 postoperatively and 2.6 at the last follow-up examination. Although the patients with valgus deformity had smaller degree of arthrosis preoperatively than patients with varus deformity, arthrosis developed equally in both groups despite the fact that the operation was performed. We measured joint tilt according to Shoja and Insall. The patients with varus deformity had joint tilt 7 degrees before operation, -4.3 degrees after operation and -2.4 degrees at the last control. The patients with varus deformity had femurotibial angle of 185 degrees preoperatively, 173 degrees postoperatively, and 175 degrees at the last follow up examination. The average revarisation of 2 degrees occurred despite overcorrection. The patients with valgus deformity had femurotibial angle of 164 degrees preoperatively, of 178 degrees postoperatively and of 180 degrees at the last follow-up examination. Revarisation progressed 2 degrees on average after varisation osteotomy was performed in the knees with valgus deformity. There was no statistically significant correlation between pain and femurotibial angle and pain and degree of arthrosis preoperatively, postoperatively and at the last follow-up examination. The patients were assessed according to the system developed at the Hospital for Special Surgery (HSS). The mean preoperative HSS score was 2.91 (2.82 varus and 3.33 valgus deformity), and postoperative 4.47 (4.42 varus and 4.47 valgus). The mean score at the last follow-up evaluation was 4.05 (varus 4.03 and valgus 4.13). The patients assessed the improvement themselves and it was 1 to 14 (6.1) years. Although the indications for aloarthroplasty of the knee are more frequent nowadays, the authors recommend not to forget corrective osteotomy in the treatment of angular deformity of the knee with osteoarthritis. PMID- 11210821 TI - [Exercise-induced bronchospasm and its prevention]. AB - Exercise-induced bronchospasm (EIB) is a type of nonspecific bronchial hyperreactivity. It affects mostly children and younger adults with asthma (75% 95%) and allergic rhinitis (40%), but it is also found in 3-11% of the nonasthmatic and nonatopic younger population. Pathophysiology of this phenomenon is not clear and there are some attempts to explain it with hyperosmolality of bronchial epithelia, exchange of heat and water (reactive hyperemia) in airways and reflex vagal bronchospasm. Unrecognized and uncontrolled symptoms of EIB can lead patients to avoid general and occupational physical activities and sports. Diagnosis of EIB is focused on medical history and on pulmonary function testing after standardized exercise testing protocols on treadmill, cycle ergometer or by free running. Non-pharmacological and pharmacological prophylactic measures are the most important approach in the therapy of EIB. Inhalation of beta 2-agonists or cromolyns is the first choice in pharmacological prevention of EIB. With adequate therapy, symptoms of EIB can be controlled enough to maintain everyday as well as sports activities. PMID- 11210822 TI - [Continuing medical education in Croatia and the European Union]. AB - The Continuing Medical Education (CME), with attention to other forms of Continuing Professional Development (CPD) in Croatia and the today endeavors in the European Union, are presented. In European Union the formal CME is in its starting. The "European Accreditation Council for Continuing Medical Education" (EACCME) of the UEMS is established, which has formulated the principles of continuing education, the credit hours and their realizing, that would enable the mutual recognition of education in all European countries. In Croatia the starting of CME was at beginning of the 20th century, when the professional societies of Croatian Medical Association were founded. CPD was almost exclusively connected to activities of "Andrija Stampar" School of Public Health, to the School of Medicine in Zagreb and partly in Rijeka, which established a great number of postgraduate studies. The CME i.e. the courses of education were tightly connected to activities of the Croatian Medical Association, of its professional societies and its Academy of Medical Sciences, but also to activities of School of Medicine in Zagreb and Rijeka, and recently in Split and Osijek. Since 1995 the third partner, the Croatian Medical Chamber joined too. The number of CME meetings during 1998 is presented. The approximate calculation for needed annual courses of CME for all medical specialties in Croatia is presented. The formation of the National Authority for CME is suggested, in which all the interested institutions should be represented. PMID- 11210823 TI - [Communicable diseases in Croatia]. PMID- 11210824 TI - Can gene therapy overcome the problem of hypoxia in radiotherapy? PMID- 11210825 TI - Hydrocephalus in mice following X-irradiation at early gestational stage: possibly due to persistent deceleration of cell proliferation. AB - The pathogenesis of X-ray-induced congenital hydrocephalus was studied. Pregnant mice were irradiated at 1.4 Gy on gestational day 7 (G7). Four hours after irradiation, extensive cell death was evident in the neuroepithelium and underlying mesoderm of the head region, and proliferating cell nuclear antigen (PCNA)-immunoreactive cells almost disappeared. Embryos with thinner lamina terminalis of the telencephalon, when compared with that of the control, were found in the irradiated group on G9. As early as G11 in some irradiated embryos the telencephalic wall was thinner and lateral ventricles were larger than those of the control. The choroid invagination from the lamina terminalis began on G11 in the control brain, but not in the affected brain. During the following development, fetuses with readily apparent hydrocephalus were consistently found among irradiated fetuses. In these brains the brain mantle was thinner, the corpus striatum and thalamic regions were smaller, and lateral ventricles were larger than those of the control. Even on G11 and G13 the frequencies of PCNA positive cells in the brain mantle and other brain regions were lower in the hydrocephalic brain than those of the control, suggesting a decelerated proliferation of successive cell generations following exposure to X-rays. The cerebral aqueduct was open in the hydrocephalic brain during the fetal period when the lateral ventricles were dilated. The head was vaulted after birth but the cerebral aqueduct was not completely occluded even in these animals. These findings suggested that cell death in the neuroepithelium followed by a persistent deceleration of neural cell proliferation, resulting in the hypoplasia of brain parenchyma with compensatory ventricular dilatation, is important for the establishment of hydrocephalus. PMID- 11210826 TI - The effect of caffeine on p53-dependent radioresponses in undifferentiated mouse embryonal carcinoma cells after X-ray and UV-irradiations. AB - The effect of caffeine was studied on the radioresponses of undifferentiated mouse embryonal carcinoma cells (EC cells) with or without the functional p53. The radioresponses studied included radiosensitivity, the activation of p53, apoptosis with characteristic DNA ladder formation and cell cycle progression. An undifferentiated mouse EC cell line, ECA2, and a newly established p53-deficient EC cell line, p53 delta, were used in the present study. The status of the p53 gene did not significantly affect the colony survivals of undifferentiated EC cells to X-rays and UV. Although a post-irradiation treatment with caffeine sensitized both lines to X-rays marginally, the sensitization was prominent for UV regardless of the p53 status of the cells. The activation of a p53 responsible lacZ reporter construct was observed in stably transfected ECA2 cells after X-ray and UV irradiations. Caffeine suppressed the X-ray induced activation of the lacZ reporter, while it drastically enhanced the activation after UV irradiation. X rays and UV readily triggered the apoptosis of ECA2 cells with the characteristic DNA ladder. Although UV-induced DNA ladder formation was enhanced by caffeine, that induced by X-rays was unaffected. Therefore, the effects of caffeine on the p53-dependent radioresponses were found to be agent specific: suppression for the X-ray induced and augmentation for the UV induced. In contrast to p53-proficient ECA2 cells, smear-like DNA degradation was observed for irradiated p53 delta cells, suggesting the presence of a mode of cell death without DNA ladder formation. UV induction of the smear-like DNA degradation was enhanced in the presence of caffeine. Regardless of the state of the p53 gene, G1/S arrest was not observed in X-ray and UV irradiated EC cells. X-ray induced G2/M arrest in both lines, which was abrogated by caffeine, while G2/M arrest after UV was unaffected by a caffeine treatment. These results indicate that the radioresponses of undifferentiated EC cells differ considerably from those of somatic cells, and that these radioresponses were modulated by a post-irradiation treatment with caffeine. PMID- 11210827 TI - UVC-induced apoptosis in human epithelial tumor A431 cells: sequence of apoptotic changes and involvement of caspase (-8 and -3) cascade. AB - Human epidermoid tumor A431 cells underwent apoptosis following exposure to ultraviolet C (UVC). The apoptosis was of the interphase death type, and mostly occurred within one cell cycle, independent of the cell-cycle phases. We further examined the detailed sequential order of apoptotic changes in cells after UVC exposure and the involvement of caspases using six caspase inhibitors. The loss of mitochondrial transmembrane potential (delta psi m) appeared in the earliest phase; subsequently, the chromatin condensation and DNA-fragmentation occurred. Cell shrinkage and loss of the plasma-membrane integrity, judged by propidium iodide (PI) staining, were observed in the later phase. A broad-spectrum caspase inhibitor, z-VAD-fmk, completely prevented all apoptotic changes, except for the depletion of delta psi m. Both Ac-DEVD-CHO and Ac-IETD-CHO, inhibitors of caspase -3 and -8, respectively, effectively inhibited typical chromatin condensation to almost the same extent. However, the nuclei still showed partial condensation. A caspase -9 inhibitor, Ac-LEHD-CHO, did not prevent chromatin condensation, though it partially inhibited cell-size reduction and PI-stainability. None of the caspase inhibitors could inhibit the delta psi m reduction. These results strongly suggest that the collapse of delta psi m is not a part of the central apoptotic machinery, and that caspase cascade(s), especially caspase-8 to -3, play an important role in UVC-induced apoptosis in A431. PMID- 11210828 TI - Ionizing radiation and bacterial challenge alter splenic cytokine gene expression. AB - Irradiation increases susceptibility to bacterial infection. Exogenous proinflammatory cytokines can alter the response of mice to gamma radiation, but the role of endogenous inflammatory cytokines after bacterial infection in irradiated animals is not known. Gene expression of hematopoietic (GM-CSF) and proinflammatory (IL-1 beta, IL-6 and TNF-alpha) cytokines were examined in spleens of B6D2F1/J female mice after irradiation alone (1.0- and 7.0-Gy), and after irradiation followed by Klebsiella pneumoniae s.c. challenge 4 days postirradiation by using the reverse transcription-polymerase chain reaction (RT PCR) and Southern blot hybridization. At 4, 8, and 24 h after bacterial challenge in 7.0-Gy-irradiated mice, GM-CSF mRNA increased (p < 0.05). TNF-alpha mRNA in irradiated mice were slightly decreased, whereas after bacterial challenge, TNF alpha mRNA elevated at 30 h in 7.0-Gy-irradiated mice; at 4, and 8 h in 1.0-Gy irradiated mice, and at 1 h in sham-irradiated mice (p < 0.05). IL-6 mRNA displayed a biphasic response in 7.0-Gy-irradiated mice, and, after bacterial challenge, in both irradiated mice (1.0- and 7.0-Gy) and sham-irradiated mice. IL 1 beta mRNA remained at or below normal for 8 h and increased at 24 h after bacterial challenge on day 4 in 7.0-Gy-irradiated mice. These results indicate that sublethal gamma radiation alters the patterns of the hematopoietic and proinflammatory cytokine responses to bacterial challenge in vivo. Consequently, treatment protocols may need to take into account changes in cytokine gene responses to resolve infection after irradiation. PMID- 11210829 TI - Expression of ICAM-1 and acute inflammatory cell infiltration in the early phase of radiation colitis in rats. AB - Inflammatory cell infiltration of the colon is observed at an early stage of radiation-induced colitis. The emigration of inflammatory cells from the circulation requires interactions between cell adhesion molecules on the vascular endothelium and molecules on the surface of leukocytes. To elucidate this process, the present work analyzes the kinetics of the expression of intercellular adhesion molecule-1 (ICAM-1) and the accumulation of inflammatory myeloperoxidase (MPO)-positive cells in relation to the appearance of acute radiation colitis prior to an overt radiation-induced ulcer. Colon tissues were obtained from Wistar Kyoto rats at various times after 22.5 Gy irradiation to the rectum. Histologically, crypt depletion and numerous inflammatory cells were observed 4 days after irradiation, and mucosal ulcer 6 days after irradiation. ICAM-1 immunopositivity was present in the endothelial cells of small vessels in the mucosa of both control and irradiated rats. ICAM-1 mRNA expression was detected in normal colon and irradiated colon by reverse transcription-PCR. In Northern blotting, ICAM-1 mRNA levels were found to increase markedly in the irradiated colon compared to the normal colon. In Western blotting. ICAM-1 protein expression also increased with a peak one day after irradiation, and remained elevated up to 6 days thereafter. The number of MPO-positive cells in lamina propria mucosa increased in a time-dependent fashion from 6 h to 6 days after irradiation. These data suggest that up-regulation of ICAM-1 in endothelial cells and accumulation of MPO positive cells play important roles in the development of radiation-induced colonic ulcer. PMID- 11210830 TI - Exposure to strong magnetic fields at power frequency potentiates X-ray-induced DNA strand breaks. AB - We examined the effect of an extremely low-frequency magnetic field (ELFMF) at 5, 50 and 400 mT on DNA strand breaks in human glioma MO54 cells. A DNA damage analysis was performed using the method of alkaline comet assay. The cells were exposed to X-rays alone (5 Gy), ELFMF alone, or X-rays followed by ELFMF at 4 degrees C or on ice. No significant difference in the tail moment was observed between control and ELFMF exposures up to 400 mT. X-ray irradiation increased DNA strand breaks. When cells were exposed to X-rays followed by ELFMF at 50 and 400 mT, the tail moment increased significantly compared with that for X-rays alone. When the exposure of cells was performed at 37 degrees C, no significant change was observed between X-rays alone and X-rays plus 400 mT. We previously observed that exposure to 400 mT ELFMF for 2 h increased X-ray-induced mutations (Miyakoshi et al, Mutat. Res., 349: 109-114, 1996). Additionally, an increase in the mutation by exposure to the ELFMF was observed in cells during DNA synthesizing phase (Miyakoshi et al., Int. J. Radiat. Biol., 71: 75-79, 1997). From these results, it appears that exposure to the high density ELFMF at more than 50 mT may potentiate X-ray-induced DNA strand breaks. PMID- 11210831 TI - Similarity between the effects of carbon-ion irradiation and X-irradiation on the development of rat brain. AB - The effects of carbon-ion irradiation and X-irradiation on the development of rat brain were compared. Twenty pregnant rats were injected with bromodeoxyuridine (BrdU) at 9 pm on day 18 of pregnancy and divided into five groups. Three hours after injection (day 19.0) one group was exposed to 290 MeV/u carbon-ion radiation by a single dose of 1.5 Gy. Other groups were exposed to X-radiation by 1.5, 2.0 or 2.5 Gy, or sham-treated, respectively. Fetuses were removed from one dam in each group 8 h after exposure and examined histologically. Extensive cell death was observed in the brain mantle from the irradiated groups. The cell death after 1.5 Gy carbon-ion irradiation was remarkably more extensive than that after 1.5 Gy X-irradiation, but comparable to that after 2.0 Gy or 2.5 Gy X irradiation. The remaining rats were allowed to give birth and the offspring were sacrificed at 6 weeks of age. All of the irradiated offspring manifested microcephaly. The size of the brain mantle exposed to 1.5 Gy carbon-ion radiation was significantly smaller than that exposed to 1.5 Gy X-radiation and larger than that exposed to 2.5 Gy X-radiation. A histological examination of the cerebral cortex revealed that cortical layers II-IV were malformed. The defect by 1.5 Gy carbon-ion irradiation was more severe than that by the same dose of X irradiation. Although the BrdU-incorporated neurons were greatly reduced in number in all irradiated groups, these cells reached the superficial area of the cortex. These findings indicated that the effects of both carbon-ion irradiation and X-irradiation on the development of rat brain are similar in character, and the effect of 1.5 Gy carbon-ion irradiation compares to that of 2.0-2.5 Gy X irradiation. PMID- 11210832 TI - Effects of the restriction of food and water intake on the distribution and retention of radioiodine in mice. AB - The effects of the restriction of food and water intakes on gastrointestinal absorption, distribution to organs and excretion of 131I were investigated in C3H/He mice. The animals were divided into four groups and administered orally 37 kBq carrier-free Na 131I in 0.25 ml normal saline. One group of animals was given food and water ad libitum throughout the experimental period. Food and water to the remaining groups were restricted before and/or after the administration of 131I. The animals in each group were sacrificed 4 h and 24 h after administration, and the activity of 131I in thyroid, blood, liver, kidney, gastrointestinal tract, urine, feces, and carcass was measured. There was a significant increase in the retention of 131I in the thyroid and the concentration of 131I in the blood due to the restriction of food and water after the administration of 131I. In contrast, a significant decrease in the urinary excretion was observed in these animals. In those animals, which fasted before administration only, the retention of 131I in the thyroid and other organs were decreased. Therefore, for an accurate diagnosis and effective therapy with radioiodine as well as effective radiation protection, the intake of food and water should be taken into account. PMID- 11210833 TI - RAMC Journal 1948 Vol 91 101-124. The Burma campaigns--1942-1945. A history of casualty evacuation. PMID- 11210834 TI - [Effectiveness of lymphotropic therapy in patients with tuberculosis in relations to genetic markers]. AB - To study whether a combination of the carriage of genetic blood markers: haptoglobin phenotypes and red blood cell glucose-6-phosphate dehydrogenase, 60 patients with destructive tuberculosis were given a new drug treatment regimen by using regional lymphotropic therapy with 10% isoniazid. The efficiency of the treatment and residual changes were found to be directly related to what a patient has as genetic background. Defining the types of combinations of genetic markers may predict the course of disease, the efficiency of treatment, and outcomes. PMID- 11210835 TI - [Hepatorenal correlations in patients with pulmonary tuberculosis in the presence of viral hepatitis B markers and organic chlorine pesticides: radionuclide studies]. AB - Excretory hepatic function (EHF) and effective renal plasma flow (ERPF) were studied in 115 patients with pulmonary tuberculosis by the data of radionuclide studies. The patients were divided into 2 groups: Group 1 included 89 patients whose blood samples showed viral hepatitis B markers (VHBM) and organic chlorine pesticides (OCP) and Group 1 comprised 26 patients without VHBM and OCP. More than 50% of the examinees were found to have impairments in both EHF and ERPF. In some of them, these disorders progressed during treatment. There was a correlation between these parameters, which makes it necessary to search for new pathogenetic exposures in order to improve hepatic and renal functions in patients with blood VHBM and OCP. PMID- 11210836 TI - [Early surgical treatment of new restrictive forms of pulmonary tuberculosis]. AB - The outcomes of surgical treatment were analyzed in 264 new cases of restrictive pulmonary tuberculosis subjected to pulmonectomy without pretreatment with drugs in the preoperative period. Sixty one patients who had refused to have surgery or operated on after treatment were as a control. Indications for such policy were defined. These included limited tuberculomas and cavernous tuberculosis without local seeding, perifocal infiltration, exacerbations and preserved cellular and humoral immunity and non-specific protection factors. The outcomes of surgical interventions in the experimental group were slightly better. They had fewer complications, rapid recovery of working capacity, low per cent of disability than patients operated on after preoperative chemotherapy. There was no increase in the incidence of relapses. PMID- 11210837 TI - [Outcomes of surgical interventions in patients with infiltrative pulmonary tuberculosis]. AB - Thirty eight patients underwent surgery. The most significant causes of ineffective therapeutical measures in patients were their treatment incompetences (100%), multidrug resistance of Mycobacteria tuberculosis (47.3%), lung tissue destruction (68.4%), concomitant alcoholism (47.3%), relapses of specific lung damage (23.7%). If medical treatment is ineffective in patients with infiltrative pulmonary tuberculosis for 6 months, it is expedient to make a surgical intervention that promotes recovery (96%) and restore working capacity (84%) in them. PMID- 11210838 TI - [Effects of ftorotan and isoflurane on homeostatic parameters in patients with pulmonary tuberculosis ar reoperation]. AB - Metabolic parameters were studied in 32 patients who underwent resurgery for complicated forms of pulmonary tuberculosis. Isoflurane caused deeper anesthesia than did ftorotan, exerted no toxic effect on hepatic function, did not alter the levels of serum immunoglobulins in the plasma of patients in the early postoperative period, which allows it to be recommended for its use in this group of patients. PMID- 11210839 TI - [Enhancing the impact of chemotherapy of tuberculosis with parenteral administration of dissolved ozone]. AB - Thirty three patients with acute progressive chronic pulmonary tuberculosis who were admitted to be intolerable since they had gross damage and gained no benefits from chemotherapy due to the multidrug resistance of Mycobacteria tuberculosis were given an additional course of intravenous dissolved ozone administration (PO3). Before PO3 administration, more than half (57.4%) of the patients received only 1 or 2 antituberculous drugs (ethambutole and ethionamide or ethambutole and oprofloxacin). PO3 produced a pronounced disintoxifying effect, resulting in cessation of bacterial isolation. The stabilization of a tuberculous process was verified by clinical, X-ray, and laboratory studies in 75.8% of patients. This made it possible to perform bulky operations on the lung. When there was a postoperative progression of the underlying process in the single lung, chemotherapy was supplemented by intravenous PO3, which also promoted the stabilization of the process. The use of PO3 expands the spectrum of used agents and enhances the impact of chemotherapy in the treatment of patients isolating multidrug-resistant M. tuberculosis in both pre- and postoperative periods, this increases the rate of operability in the most serious patients. PMID- 11210840 TI - Outside interests. PMID- 11210841 TI - The effect of androstenedione/estrone supplementation on cortical and cancellous bone in the young intact female monkey: a model for the effects of polycystic ovarian disease on the skeleton? AB - The goal of this study was to determine the effects of chronically elevated blood androstenedione and estrone levels on the quality and quantity of both cancellous (trabecular) and cortical bone in a young (mean age 9.4 years) female primate model (M. fascicularis). Thirteen intact female monkeys received continuous androstenedione/estrone supplementation via subcutaneous implants over a 24-month period to simulate the human condition known as polycystic ovarian disease (PCOD). A group of 16 untreated intact age-matched female monkeys served as controls. Lumbar spine and whole body bone mineral density (BMD) status was determined mid-study by dual photon absorptiometry (DPA); subsequent analysis of the bone related to data obtained following the 2-year treatment period without further BMD measurement. Bone markers, including serum acid phosphatase, total bone alkaline phosphatase, bone gla protein and tartrate-resistant acid phosphatase were measured at the end of the study. At necropsy, the lumbar vertebrae and femora were recovered in order to analyze the bone mineral quality and quantity of cancellous and cortical bone respectively and to compare these with the control group. Mineralization profiles of the vertebrae and femora were obtained using the density fractionation technique. Chemical analysis of the three largest fractions retrieved by density fractionation was performed to evaluate differences in %Ca, %P, Ca/P ratio and mineral content (%Ca + %PO4) between control and experimental groups. In addition, unfractionated bone powder was examined by X-ray diffraction to identify any changes in crystal size. Coronal sections of vertebrae were analyzed for structural parameters using histomorphometry and image analysis. Cross-sections taken at the midshaft diaphyseal femora were analyzed for structural macroscopic and intracortical parameters. There was a significant increase in BMD at the L2-L4 region in the treatment group compared with the control groups (p < 0.005) as measured at 1 year into the trial. Serum acid phosphatase was significantly lower (p < 0.05) in the treatment group compared with the controls near study termination. A nonsignificant shift in the mineralization profile of the vertebrae towards less dense bone was observed in the treatment group, while there was a significant shift in the mineralization profile towards more dense bone in the treated femora compared with controls (p < 0.05) after a 2-year period. There was no difference between treatment and control groups in terms of size/strain of the cortical or cancellous bone crystal as detected by X-ray diffraction. There was a significant increase in cancellous bone area (B.Ar.) (p < 0.02) and a significant increase (p < 0.05) in mean trabecular width with a corresponding decrease in trabecular separation (p < 0.03) in the experimental group compared with the controls. There were no significant changes in osteoid parameters (perimeter, area or width) or eroded perimeter measurements in the experimental group compared with the controls. In the experimental group, trabecular strut analysis showed a significant increase in the number of nodes (p < 0.02) and in the total strut length (p < 0.003) compared with the controls. There was also a significant increase in the node to node (p < 0.04) and node to terminus (p < 0.004) strut length in the treatment group compared with the controls. A significant increase in B.Ar. without concurrent indices of ongoing remodelling differing from controls suggests that cancellous bone of the vertebral body in the treated young female primate had been receptive to the anabolic stimulus of androstenedione/estrone supplementation over the 2-year period. In contrast, macroscopic parameters of cortical bone such as perimeter, area and width were preserved over the 2-year course, while intracortical remodeling was evident with increased percent porosity (p < 0.001), osteonal bone (p < 0.01) and osteonal density (p < 0.01) observed in the treatment group compared with the controls. The endocrine profile of both elevated androstenedione and estrone levels in an intact female primate of reproductive age may identify differential effects of the condition known as polycystic ovarian disease on the skeletal compartments. PMID- 11210842 TI - Biologist webwatch. PMID- 11210843 TI - Biologist webwatch. PMID- 11210844 TI - European Science Foundation policy briefing: use of animals in research. PMID- 11210845 TI - Scientific procedures on living animals in Great Britain 1999. PMID- 11210846 TI - Greater protection of rats, mice and birds in USA. PMID- 11210847 TI - Vote of thanks for Dr Jon Richmond's second Annual FRAME Lecture. PMID- 11210848 TI - LASA meeting on genetically modified research animals: applications, challenges and ethical use. PMID- 11210850 TI - Selected titles. PMID- 11210849 TI - RSPCA/UFAW rodent welfare meeting. Universities Federation for Animal Welfare. PMID- 11210851 TI - Sialoblastoma: report of a congenital case with dysembryogenic alterations of the adjacent parotid gland. PMID- 11210852 TI - Hepatocellular carcinoma with solitary metastasis in pleomorphic adenoma of the submandibular gland. PMID- 11210853 TI - Lipomatous polyposis of the colon. PMID- 11210854 TI - Pseudomembranes in collagenous colitis. PMID- 11210855 TI - Newly-developed diamond points for conservative operative procedures. AB - The rapid decrease in the size of dental restorations has increased the demand for the smallest rotary cutting instrument possible. The width of cavities prepared with two experimental diamond points and the smallest commercial diamond point were compared and significant differences found. SEM observation of the head surfaces of the three diamond points revealed that the experimental points had comparable cutting characteristics with the commercial diamond point. PMID- 11210856 TI - Effect of collagen removal on shear bond strength of two single-bottle adhesive systems. AB - This study evaluated the effect of collagen removal on the shear bond strength for two single-bottle adhesive systems. The ultrastructure of the dentin after treatments and the dentin-resin interface were examined under SEM. The buccal and lingual surfaces of 80 extracted human third molars were ground to expose dentin. Teeth were randomly assigned to four groups and received the following treatments: Group 1(P&B 2.1), Prime & Bond 2.1 adhesive was applied according to the manufacturer's directions and Restorative Z100 composite resin was bonded to the dentin surface; Group 2 (P&B 2.1/NaOCl), the same procedures were followed as for Group 1 except that the surfaces were treated with 10% sodium hypochlorite (NaOCl) for one minute after acid conditioning; Group 3 (SB), Single Bond (3M) was applied according to the manufacturer's recommendations; Group 4 (SB/NaOCl), the same procedure was followed for Group 2, using Single Bond. The specimens were stored in humidity at 37 degrees C for 24 hours and tested in a shear mode at a crosshead speed of 0.5 mm/minute. The Kruskal-Wallis test and Multiple Comparisons were used for statistical analysis of the data. A one-minute exposure of dentin to 10% NaOCl following acid conditioning resulted in a significant increase of the dentin shear bond strength for Prime & Bond 2.1. The same treatment for Single Bond resulted in a significant reduction in bond strength. Groups 1 and 3 were not statistically different from each other. The presence of a collagen layer resulted in the formation of a hybrid layer and similar values of adhesion for both adhesive systems. The results may suggest that collagen removal improves the bond strength for this acetone-based adhesive system but several such systems would need to be investigated. PMID- 11210857 TI - Immunocytochemical detection of MMP-3 and -10 expression in hepatocellular carcinomas. AB - Structural changes in the extracellular matrix (ECM) are necessary for cell migration during tissue remodeling and tumor invasion. The matrix metalloproteinases (MMPs) and their inhibitors have been shown to be critical modulators of ECM composition and are thus crucial in neoplastic cell invasion and metastasis. Expression of MMP-2, -3, -9, -10, and -13 was investigated in human hepatocellular carcinomas (HCCs) employing an indirect alkaline phosphatase conjugated immunocytochemical technique. Evaluation of the results was based on (a) the persent of neoplastically transformed cells/surrounding stroma that reacted positively and (b) a measure of staining intensity [graded from A (highest) to D]. The two forms of stromelysin, MMP-3 and -10, share 82% sequence homology, but exhibit differences in cellular synthesis and inducibility by cytokines and growth factors in vitro. Strong overall expression of MMP-3 and -10 was found in HCCs, especially in the ECM adjacent to blood vessels. Positive immunoreactivity could be seen for these two MMPs in the ECM surrounding over 90% of the neoplastically transformed cells (++++), and the staining intensity was also the strongest possible (A,B). No immunoreactivity was detected using antibodies directed against MMP-2, -9, and -13. PMID- 11210858 TI - [Matrix metalloproteinases. Point of attack for a new cancer therapy]. PMID- 11210859 TI - Laryngeal preservation with supracricoid partial laryngectomy results in improved quality of life when compared with total laryngectomy. AB - OBJECTIVES/HYPOTHESES: Study 1: To assess the oncologic outcome following supracricoid partial laryngectomy (SCPL). Study 2: To compare the quality of life (QOL) following SCPL to total laryngectomy (TL) with tracheoesophageal puncture (TEP). Study 3: To analyze whole organ TL sections to determine the percentage of lesions amenable to SCPL STUDY DESIGN: Study 1: A retrospective review of patients who underwent SCPL. Study 2: A non-randomized, prospective study using QOL instruments to compare patients who underwent either SCPL or TL Study 3: A retrospective histopathologic study of TL specimens assessed for the possibility of performing an SCPL. METHODS: Study 1: Twenty-five patients with carcinoma of the larynx underwent SCPL between June 1992 and June 1999. Various rates of oncologic outcome were calculated. Study 2: Thirty-one patients participated in the QOL assessment. This included the SF-36 general health status measure, the University of Michigan Head and Neck Quality of Life (HNQOL) instrument, and the University of Michigan Voice-Related Quality of Life (VRQOL) instrument. Study 3: Ninety surgical specimens were obtained and studied from the total laryngectomy cases in the Tucker Collection. Multiple sites were evaluated for the presence of carcinoma A computer program was written to classify whether the patient was amenable to SCPL. RESULTS: Study 1: The overall local control rate was 96% (24/25). The local control rate following SCPL with cricohyoidoepiglottopexy (CHEP) was 95% (20/21). The local control rate following SCPL with cricohyoidopexy (CHP) was 100% (4/4). Study 2: The SCPL had significantly higher domain scores than TL and TEP in the following categories for the SF-36: physical function, physical limitations, general health, vitality, social functioning, emotional limitations, and physical health summary. The significantly higher domains for the SCPL when compared with the TL and TEP for the HNQOL were eating and pain. Finally, when voice-related QOL was assessed with the V-RQOL, the domains of physical functioning and the total score were significantly better with SCPL when compared with TL and TEP. Study 3: Forty of 90 (44%) laryngeal whole organ specimens were determined to be resectable by SCPL. In 16 (18%) specimens, the patients could have undergone SCPL with CHEP and in 24 (27%) specimens the patients could have undergone SCPL with CHP. Among the 40 (44%) specimens determined to be able to have undergone SCPL, 19 were glottic (1 T1, 15 T2, 3 T3) and 21 were supraglottic (9 T2, 12 T3). CONCLUSIONS: 1) A review of the literature and an analysis of the data in this study indicate that excellent local control may be expected following SCPL. 2) The QOL following SCPL, as measured by three validated QOL instruments, is superior to TL with TEP. 3) A histologic assessment of whole organ sections of TL specimens indicates that many patients who have been subjected to TL may have been candidates for SCPL. 4) If the indications and contraindications are rigorously adhered to, SCPLs are reasonable alternatives to TL in selected cases. PMID- 11210860 TI - Steroid-dependent anosmia. AB - OBJECTIVE: To document the response to steroids in patients remaining anosmic following endoscopic nasal and sinus polypectomy. STUDY DESIGN: A prospective study of 24 patients with nasal and sinus polyps who were anosmic prior to endoscopic nasal and sinus surgery. Those who remained anosmic after surgery were treated with steroids. Most patients had asthma, allergic rhinitis, or both. A few had aspirin sensitivity. METHODS: All 24 patients had testing of their sense of smell before and after surgery. Those who remained anosmic postoperatively were first treated with topical nasal and then oral steroids and then tested again. RESULTS: Twelve of the 24 remained anosmic after surgery and were found to be unresponsive to nasal steroids, but oral steroids were found to restore the sense of smell to normal in most patients. Few patients continued to take the medication for long periods of time mainly because of a fear of side effects. Recent studies have suggested the role of systemic steroids in olfactory secretion, which may explain the mechanism for this response. CONCLUSION: Patients who remain anosmic after the removal of nasal and sinus polyps can be treated with oral steroids resulting in improvement of their sense of smell. Further research is needed on a molecular level to determine the reason for this and also why oral but not nasal steroids are helpful in these patients. PMID- 11210861 TI - Cancer induction in the DMBA hamster cheek pouch: a modified technique using a promoter. AB - OBJECTIVE: To evaluate a modified method of carcinogenesis induction using the 9,10-dimethyl-1,2-benzanthracene (DMBA) sustained-release suture technique followed by arecaidine promotion in the hamster cheek pouch model. STUDY DESIGN: Prospective, controlled animal study. METHODS: Number 3-0 cotton sutures were impregnated with DMBA and coated with silicone elastomer. These sutures were placed in the cheek pouch of Syrian hamsters in the submucosal space to a length of approximately 1.5 cm. The suture placement was confirmed every 2 weeks and replaced if lost. After 12 weeks, the DMBA-coated sutures were removed. The cheek pouches were everted and painted with a solution of arecaidine three times weekly for up to an additional 4 weeks or until the tumor reached a size of 100 mm2. RESULTS: We placed sutures in 165 Syrian hamster cheek pouches. Of these, 133 hamsters (80.6%) produced squamous cell carcinomas that reached a size of 100 mm2 and then were randomly selected for treatment in a new drug trial. Twenty-six hamsters (15.8%) were found dead and 6 (3.6%) were killed because of severe inflammation. CONCLUSIONS: The DMBA hamster cheek pouch model is a reliable and efficient animal model for inducing squamous cell carcinoma and can be used to study upper aerodigestive tract tumors. PMID- 11210862 TI - Facial purpura. AB - OBJECTIVES: Patients with facial purpura can have acute and dramatic illnesses. For this reason, the clinician must be aware of certain diagnoses that can present as facial purpura and know how to initiate treatment efficiently. According to our review of the literature, no paradigm currently exists for the diagnosis and management of facial purpura Our goal is to develop a schema for the identification and management of facial purpura. STUDY DESIGN: Case series. METHODS: A case series of five cases is presented followed by a systematic development of a differential diagnosis based on etiology of the lesion. RESULTS: Facial purpura can be classified into conditions that are primarily or secondarily vasculitic, thrombocytopenic, neoplastic, infectious, toxic, and miscellaneous, which encompasses episodic reports that do not fit into the other categories. A paradigm to diagnose patients with facial purpura is developed based on clinical presentation and etiology. To demonstrate the utility of our algorithm, the five cases presented are re-examined using the algorithm. To our knowledge, this represents the first reported series of facial purpura in the modern English literature. A flow chart based on our diagnostic paradigm is presented. CONCLUSION: Clinicians caring for patients with facial purpura must recognize the acute conditions that require emergent medical intervention. Once these diagnoses have been considered, the clinician can employ a systematic approach to the diagnosis based on etiology. This study provides a useful reference for the otolaryngologist when encountering a patient with facial purpura. PMID- 11210863 TI - A comparison of monopolar electrosurgery to a new multipolar electrosurgical system in a rat model. AB - OBJECTIVES/HYPOTHESIS: The purpose of this study is to compare collateral tissue damage and wound healing in incisions created by electro-dissociation and conventional electrosurgery. Conventional electrosurgery has been used as an alternative to the scalpel to improve hemostasis. However, the heat generated by this instrument can cause tissue damage surrounding the incision, limiting its use around nerves and large blood vessels. A new technology, Coblation (Arthrocare Corp., Sunnyvale, CA), uses "electro-dissociation" to achieve similar results by creating charged particles from a conductive medium to make an incision while simultaneously achieving hemostasis. This new approach to electrosurgery may reduce soft tissue damage. STUDY DESIGN: METHODS: Two prospective, matched design experiments were performed. In experiment I, both devices were set at the same electrical power in watts and then used to create an incision on the tongue of rats. In experiment II, the electrical power settings of both devices were adjusted until they created incisions of the same size. Epithelial destruction and collateral tissue damage were measured in histologically prepared tissue in both experiments, and the wound healing process was observed in experiment II at 0, 3, 7, and 14 days after surgery. RESULTS: The results showed that the electro-dissociation method created significantly less epithelial destruction and collateral tissue damage in both experiments. Granulation tissue formation was also significantly less extensive in the electrodissociation-induced incision after 7 and 14 days of recovery. CONCLUSIONS: Wound healing may be faster than with conventional electrosurgery if the Coblation device is used. PMID- 11210864 TI - Botulinum toxin: basic science and clinical uses in otolaryngology. AB - The role of botulinum toxin as a therapeutic agent is expanding rapidly in otolaryngology. Botulinum toxin is a protease that blocks the release of acetylcholine from nerve terminals. Its effects are transient and nondestructive, and largely limited to the area in which it is administered. These effects are also graded according to dose, allowing for individualized treatment of patients and disorders. Botulinum toxin has been used primarily to treat disorders of excessive or inappropriate muscle contraction. In the field of otolaryngology, these include spasmodic dysphonia, oromandibular dystonia, and blepharospasm; vocal tics and stuttering; cricopharyngeal achalasia; various tremors and tics; hemifacial spasm; temporomandibular joint disorders; and a number of cosmetic applications. Botulinum toxin treatment has recently begun to show some benefit in the control of pain from migraine and tension headache. It may also prove useful in the control of autonomic dysfunction, as in Frey syndrome, sialorrhea, and rhinorrhea. In over 20 years of use in humans, botulinum toxin has accumulated a considerable safety record, and in many cases represents relief for thousands of patients unaided by other therapy. PMID- 11210865 TI - Arytenoid appearance and vertical level difference between the paralyzed and innervated vocal cords. AB - OBJECTIVES/HYPOTHESIS: In unilateral vocal fold paralysis, it has been generally accepted that the paralyzed vocal fold presents at a higher level than a normally innervated vocal fold. In this study, we correlate the appearances of the paralyzed arytenoid and the differences in level between the paralyzed and innervated vocal folds. STUDY DESIGN: Retrospective review using video-recorded images of larynx. METHODS: A total of 38 patients were selected for this study who reported symptoms of voice change attributable to a paralyzed vocal fold unilaterally. Video recordings were obtained using the laryngeal telescope. The heights were assessed according to the paralyzed positions, status (inspiration or phonation), and appearances of the paralyzed arytenoid. The appearances of paralyzed arytenoid were further clarified as the portions of the medial surface of the arytenoid that were visualized. RESULTS: In medial paralysis, the paralyzed vocal fold appeared mainly as being at an equal vertical level or as having no distinct difference from normal vocal fold during phonation. However, a few cases of medial paralysis showed a lower than normal or higher than normal vocal fold during phonation, depending on the appearance of the paralyzed arytenoid. In lateral paralysis, most of the paralyzed vocal folds were not higher than the innervated vocal folds during phonation. CONCLUSIONS: The heights of paralyzed vocal folds were variable depending on the paralyzed positions, the status of the larynx, and appearances of the paralyzed arytenoid. The fact that the paralyzed vocal fold is at a higher level than the normal vocal fold should be reconsidered. PMID- 11210866 TI - Immune dysfunction in refractory sinusitis in a tertiary care setting. AB - OBJECTIVE: To examine the contribution of the primary immunodeficiency states, which are uncommon in the general population, to refractory sinusitis. STUDY DESIGN: We retrospectively reviewed the charts of 316 patients with sinusitis who were referred to the Allergy and Immunology Clinic for immunological evaluation from 1991 to 1997. METHODS: Of the 316 patients, 79 were selected for further study. Inclusion criteria included at least one sinus surgery and/or sinusitis diagnosed by endoscopy and/or computed tomography (CT) scan at least three times in the previous year. Patients with human immunodeficiency virus (HIV), allergic fungal sinusitis, cystic fibrosis, and primary ciliary dyskinesia were excluded. The results of their immunological evaluation for atopy, T-lymphocyte function, and immunoglobulin levels were examined. RESULTS: The average age of these 79 patients was 44 years (+/- 14.5 standard deviation [SD]). They had, on average, 2.94 (+/- 2.19 SD) previous operations and had mean sinus CT scores (Lund-McKay) of 11.2 (+/- 5.0 SD). Forty of 79 (50.6%) patients had at least one positive result on skin test to an aeroallergen. Delayed hypersensitivity skin testing revealed that 22 of 55 patients (40%) were anergic. Of the 60 patients with in vitro T-lymphocyte function testing, 54.8% showed abnormal proliferation in response to recall antigens, 11.3% had decreased response to alloantigen, and 26.3% demonstrated decreased response to T-cell mitogens. Determination of quantitative immunoglobulins showed low immunoglobulin G in 14 of 78 patients (17.9%), low immunoglobulin A in 13 of 78 (16.7%), and low immunoglobulin M in 4 of 78 (5.1%). Common variable immunodeficiency (CVID) was diagnosed in 9.9% of patients, and selective IgA deficiency was found in 6.2%. CONCLUSIONS: This retrospective review reveals an unexpectedly high incidence of immune dysfunction. These results suggest that immunological testing should be an integral part of the evaluation of patients with refractory sinusitis. PMID- 11210867 TI - Changes in serum interferon-gamma, interleukin-4, and interleukin-12 cytokine levels in anti-histamine type 2-treated allergic rhinitis patients. AB - OBJECTIVES/HYPOTHESIS: Markedly elevated immunoglobulin E (IgE) synthesis characterizes allergic diseases. Interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) regulate IgE synthesis. It has been shown that immunotherapy and histamine type 2 (H2) receptor antagonists induce a clinical improvement, decrease IgE antibodies, and increase T-cell subsets, which express a suppressor function. In addition, immunotherapy brings about a reduction in the amount of IL-4 in T-cell clones of allergic individuals. The purpose of this study was to investigate the profile of cytokines IFNgamma and IL-4 that occurs in vivo in anti-H2-treated patients with allergic rhinitis (AR). METHODS: Enrolled were 65 AR patients with sensitivity to a single allergen, the Parietaria, 36 of whom were randomly assigned to treatment with ranitidine at a dosage of 1 mg/kg per day intravenously for 20 days, and 29 to placebo treatment. RESULTS: A comparison of the serum cytokine values recorded before and after anti-H2 treatment showed a significant increase in INF-gamma serum level (P = .003) and a decrease in IL-4 (P = .016). Negligible variations were found in the placebo-treated group. CONCLUSION: H2 antagonists probably induce their effects by enhancing the amount of IFN-gamma and by reducing IL-4 cytokines, which, respectively, induce a decrease and an increase in the IgE synthesis. PMID- 11210868 TI - Quantitative analysis of mucin and lectin in maxillary sinus fluids in patients with acute and chronic sinusitis. AB - OBJECTIVES: Sinusitis is characterized by quantitative and qualitative changes in mucus biosynthesis that contribute to sinus disease. In general, patients with acute sinusitis complain of purulent rhinorrhea, whereas those with chronic sinusitis complain of mucoid or mucopurulent rhinorrhea Locally produced mucin largely contributes to the high viscoelasticity of mucus in sinusitis. In this study, the authors attempt to quantify the concentrations of mucin and lectin in the maxillary sinus fluids from these patients. STUDY DESIGN: To assess the concentrations of mucin and lectin in aspirates of 11 acutely and 11 chronically inflamed maxillary sinuses, the concentration of mucin was measured by enzyme linked immunosorbent assay (ELISA) and that of lectin by sandwiched enzyme-linked lectin assay (ELLA). RESULTS: The concentrations of mucin and lectin that were measured using monoclonal antibodies (HCS 4, HCS 14, and HCS 18) and Ulex europaeus agglutinin-1 (UEA-1) in chronic sinusitis were higher than those in acute sinusitis. The concentration of total protein in chronic sinusitis was lower than that in acute sinusitis. Each mucin and lectin versus total protein ratio in chronic sinusitis was higher than that in acute sinusitis. CONCLUSIONS: These data suggest that hypersecretion in chronic sinusitis may result from locally increased mucin production. Comprehension of this mechanism may be a strategy to prevent the viscous cycle of paranasal sinus fluids in chronic sinusitis. PMID- 11210869 TI - Regulation of mucociliary motility by nitric oxide and expression of nitric oxide synthase in the human sinus epithelial cells. AB - OBJECTIVES: This study was performed to investigate the changes in ciliary beat frequency (CBF) after treatment with Larginine in the human sinus mucosa and to determine the distribution of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) in the healthy sinus mucosa. STUDY DESIGN/METHODS: CBF was measured in the sphenoid sinus mucosa of 12 patients who underwent trans-septal trans-sphenoidal hypophysectomy for the treatment of pituitary gland tumor. CBF was measured over 24 hours in Dulbecco's modified Eagle's medium (DMEM) after treatment with L-arginine, its inactive spatial isomer D-arginine, or an NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L NAME). DMEM without treatment with these materials was used as a control. Other pieces of the mucosa were exposed to L-NAME and its inactive spatial isomer D NAME after preincubation with L-arginine. The specimens were immunohistochemically stained for iNOS and eNOS. RESULTS: CBF increased 24 hours after treatment with L-arginine as compared with control groups. CBF increased in proportion to the increasing concentrations of L-arginine. There was no significant change after treatment with D-arginine or L-NAME. CBF increased after treatment with L-arginine at 30 minutes and maintained for 24 hours. L-NAME inhibited the increase in CBF by L-arginine, but D-NAME showed no such effect. Immunoreactivity to both iNOS and eNOS was frequently observed in the ciliated epithelial cells and was stronger to eNOS than to iNOS. CONCLUSIONS: From the results of this study it is suggested that nitric oxide (NO) produced by iNOS and eNOS using L-arginine may increase CBF in the healthy sinus mucosa and that NO may have a regulatory function in ciliary motility in the human sinus mucosa. PMID- 11210870 TI - Effectiveness of adenoidectomy and laser tympanic membrane fenestration. AB - OBJECTIVE: Adenoidectomy alone or with tonsillectomy (A+/-T) is an effective surgical intervention in the management of otitis media in children, especially when it is performed in conjunction with insertion of pressure equalization tubes (PETs). Otorrhea and persistent tympanic membrane (TM) perforation are frequent complications. This study evaluates the effectiveness of intermediate duration middle ear ventilation using laser tympanic membrane fenestration (LTMF) without tube insertion and as an adjunct to adenoidectomy in resolving middle ear disease within the first 90 days after surgery. STUDY DESIGN: This pilot study was a multicenter, prospective clinical cohort trial. Institutional review board approval and informed consent were obtained. The study involved four tertiary care pediatric otolaryngology departments. Fifty children (96 ears) were treated with LTMF in conjunction with A+/-T from June 1, 1998, through March 30, 1999. Ages ranged from 9 months to 12 years. Patients undergoing A+/-T who would have been recommended for PET insertion instead underwent middle ear ventilation with LTMF using the Oto-LAM device (ESC/Sharplan, Yokneam, Israel). Patients were seen at 30, 60, and 90 days postoperatively. Resolution of otitis media with effusion was determined by clinical examination, which included pneumatic otoscopy, audiometry, and tympanometry. RESULTS: Of the treated ears, 88%, 86%, and 83% had clinical resolution of middle ear disease at 30, 60, and 90 days, respectively. Preoperatively, 45% (n = 85) of ears had normal hearing; 92% (n = 49) had normal hearing at 90 days. Eighty-nine percent (n = 92) had type C2 or B tympanograms preoperatively, and 12% (n = 60) had type C2 or B at 90 days. CONCLUSION: Laser tympanic membrane fenestration in conjunction with adenoidectomy was effective in restoring normal middle ear function at 90 days post-treatment in greater than 80% of children who otherwise may have had placement of PETs. PMID- 11210872 TI - Autologous fibrin sealant reduces pain after tonsillectomy. AB - OBJECTIVES/HYPOTHESIS: Pain is a major cause of morbidity after tonsillectomy. Although various efforts have been made to reduce pain, the use of oral analgesics, which can have adverse side effects, remains the standard of care. It is hypothesized that fibrin sealant, used to achieve hemostasis and enhance healing in many surgical procedures, might help decrease pain after this operation. STUDY DESIGN: A prospective, randomized, blinded study was performed on 20 children aged 5 to 17 years who were undergoing tonsillectomy, to evaluate the efficacy of FIBRIN SEALANT in reducing postoperative pain. METHODS: All patients pre-donated 40 mL of blood from which autologous concentrated fibrinogen was prepared by cryoprecipitation. In the fibrin sealant group, fibrinogen and topical bovine thrombin were sprayed onto the surgical site to form fibrin sealant at the conclusion of tonsillectomy. The 10 patients in the control group (C) received no fibrin sealant. Patients rated their level of pain immediately after surgery and at regular intervals for 3 days after surgery using the Wong Baker Faces Pain Rating Scale (1-6). Emesis, postoperative bleeding, medications, and adverse events were also evaluated. RESULTS: At 7.00 P.M. on postoperative day (POD) 0, the mean +/- SD fibrin sealant group pain score (2.9+/-0.41 units) was significantly lower than for the C group (4.1+/-0.43 units; P < or = .05). There was also a trend in favor of less pain in the fibrin sealant group at 7:00 P.M. on POD 1, with a mean of 3.5+/-0.43 units versus 2.4+/-0.48 units for C (P = .15). The odds of a patient in C experiencing emesis were 8.16 times higher, (P < or = .05) than for patients in the fibrin sealant group. CONCLUSIONS: Fibrin sealant significantly reduced pain the evening after pediatric tonsillectomy and also decreased the chance of experiencing emesis. Thus fibrin sealant may be clinically useful as an adjunct to tonsillectomy. PMID- 11210871 TI - Prevention of vomiting after tonsillectomy in children: granisetron versus ramosetron. AB - OBJECTIVE/HYPOTHESIS: Granisetron, a selective 5-hydroxytryptamine type 3 receptor antagonist, is effective for the prevention of vomiting after tonsillectomy in children. Ramosetron (Nasea; Yamanouchi; Tokyo, Japan), another new antagonist of 5-hydroxytryptamione type 3 receptor, has more potent and longer-acting properties than granisetron (Kytril; Smith Kline Beecham, London, UK) against cisplatin-induced emesis. This study was undertaken to compare the efficacy and safety of granisetron and ramosetron for the prevention of vomiting after pediatric tonsillectomy. STUDY DESIGN: Prospective, randomized, double blinded study. METHODS: Ninety pediatric patients, aged 4 to 10 years, received intravenously granisetron 40 microg/kg or ramosetron 6 microg/kg (n = 45 each) at the end of surgery. The same standard general anesthetic technique and postoperative analgesia were used throughout. Emetic episodes and safety assessment were performed during the first 24-hour period and the next 24-hour period after anesthesia. RESULTS: The rates of patients being emesis-free during the period from 0 to 24 hours after anesthesia were 89% with granisetron and 93% with ramosetron, respectively (P = .357); the corresponding rates during the period from 24 to 48 hours after anesthesia were 71% and 93%, respectively (P = .006). No clinically serious adverse events attributable to the study drugs were observed in any of the groups. CONCLUSION: Ramosetron is a better antiemetic than granisetron for the long-term prevention of postoperative vomiting in children undergoing general anesthesia for tonsillectomy. PMID- 11210873 TI - Specificity of parotid sialendoscopy. AB - OBJECTIVE: To present our initial experience with sialendoscopy of the parotid duct. STUDY DESIGN: METHODS: Diagnostic and interventional sialendoscopy procedures were performed in 79 and 55 cases, respectively. Diagnostic sialendoscopy was used to classify ductal lesions into sialolithiasis, stenosis, sialodochitis, and polyps. Interventional sialendoscopy was used to treat these disorders. The type of endoscope used, the type of sialolithiasis fragmentation and/or extraction device used, the total number of procedures, the type of anesthesia, and the number and size of the sialoliths removed were the dependent variables. The outcome variable was the endoscopic clearing of the ductal tree and resolution of symptoms. RESULTS: Diagnostic sialendoscopy was possible in all cases, with an average duration of 26+/-14 minutes and no complications. Interventional sialendoscopy was successful in 85% of cases, with an average duration of 73+/-43 minutes (+/- standard deviation). Multiple procedures were performed in 45% of cases, general anesthesia was used in 24%, and parotidectomy in 2%. Multiple sialoliths were found in 58% of ducts and associated with more procedures under general anesthesia and longer operations. The average size of sialoliths was 3.2+/-1.3 mm; larger stones were associated with more procedures under general anesthesia, longer and multiple procedures, use of fragmentation, and sialendoscopy failures. Sialolithiasis fragmentation was required in 10% of cases, with a success rate of 70%. Semirigid sialendoscopes performed better than flexible ones. Complications were mostly minor but were encountered in 12% of cases. CONCLUSIONS: Diagnostic sialendoscopy is a new technique for evaluating salivary duct disease, a technique which is associated with low morbidity. Interventional sialendoscopy allows the extraction of sialoliths in most patients, preventing open gland excision. PMID- 11210874 TI - A simple method to estimate the secretion of saliva from minor salivary glands using iodine-starch reaction. AB - OBJECTIVE/HYPOTHESIS: This study was undertaken to detect the faculty of secretion of saliva from minor salivary glands by analyzing a color reaction on a test tape containing iodine and starch that was applied on the lower lip. STUDY DESIGN: A study involving 63 patients with oral dryness, 7 patients with Sjogren syndrome, and 70 healthy individuals was performed. METHODS: A test tape (1 x 1 cm) containing iodine and starch was set on the mucosal area anterior to the labia frenulum for 30 seconds. Because the number of blue spots was considered to correspond to the number of ostia of the salivary gland on the lower lip that was examined, the number of blue spots occurring as a reaction of iodine and starch on the test tape was counted and was compared among three groups. In addition, the relationship between the histopathological findings and the number of spots was analyzed. RESULTS: The average number of spots in the patients with oral dryness (4.52+/-3.18 [mean +/- SD]) was lower than that in healthy individuals (9.49+/-2.52, P <.01), and that in the patients with Sjogren syndrome (2.14+/ 1.35) was the lowest among all groups in the study. Moreover, this reduction in the number of spots in those patients was accompanied by histopathological changes of the minor salivary glands. CONCLUSION: These findings suggest that this simple, noninvasive method can be successfully used for the estimation of the faculty of secretion of saliva from the minor salivary glands. PMID- 11210875 TI - Microwave decalcification of human temporal bones. AB - OBJECTIVES/HYPOTHESIS: Morphological and immunohistochemical studies of human temporal bones are challenging as a result of difficulties in obtaining reliably fixed specimens and the lengthy time required for decalcification, typically 4 to 7 months. A novel method of processing human temporal bones using a microwave oven to accelerate decalcification is described. This procedure provides a rapid means of decalcifying temporal bones with good preservation of tissue morphology and antigenicity. METHODS: Human temporal bone specimens obtained at autopsy (n = 12, from specimens aged 43-91 y) were fixed within 6.5 hours of death by transtympanic perilymphatic perfusion of the inner ear. Decalcification was carried out using ethylenediaminetetra-acetic acid (EDTA) in a microwave oven and required only 3 to 6 weeks. Specimens were then dehydrated, embedded in paraffin, sectioned, and mounted on slides for morphological and immunohistochemical evaluation. RESULTS: Microscopic examination revealed no obvious artifacts attributable to the microwave decalcification process. The quality of morphological preservation was largely dependent on the postmortem fixation interval and adequacy of perilymphatic perfusion. Immunohistochemical analysis demonstrated strong positive staining for the enzyme Na,K-ATPase, an integral membrane protein. CONCLUSIONS: This study demonstrates that microwave decalcification provides an efficient and reliable means of processing human temporal bones for histological and histochemical examination. Decalcification time is significantly reduced with no apparent adverse effects on structural preservation or antigenicity. PMID- 11210876 TI - Free radical production by antibiotic-killed bacteria in the guinea pig middle ear. AB - OBJECTIVES: Oxygen free radicals are implicated in the pathogenesis of otitis media Recent investigations with animal models have demonstrated that free radical-mediated damage of the middle ear mucosa, measured as lipid hydroperoxide, occurs when the middle ear cavity is inoculated with Streptococcus pneumoniae. The present study was conducted to examine the effect of antibiotics on free radical-mediated damage in pneumococcal acute otitis media. STUDY DESIGN: Animal model of acute otitis media. METHODS: Seventy-eight guinea pigs underwent bilateral middle ear inoculation with 100 microl of 1) sterile saline as a control, 2) 50 microg/mL amoxicillin, 3) 10(7) colony forming units (CFU)/mL Streptococcus pneumoniae killed with 50 microg/mL amoxicillin, or 4) 10(7) CFU/mL S. pneumoniae. Animals were killed on postoperative day 1 or 5, and the middle ear mucosa was examined for lipid peroxidation as evidence of free radical damage. RESULTS: Mucosal lipid hydroperoxide was significantly elevated compared with control subjects on day 1 in both the antibiotic-killed S. pneumoniae group and the S. pneumoniae-infected group. On day 5, the S. pneumoniae-infected mucosa had significantly higher lipid hydroperoxide levels compared with the antibiotic killed group and the control subjects. Histological studies confirmed mucosal edema and the presence of inflammatory cells in the infected groups. CONCLUSIONS: Antibiotic-killed bacteria seem to produce free radical-mediated damage to the middle ear mucosa in the early phase of acute otitis media. The clinical implication of this study is that free radical damage to the middle ear mucosa may occur in otitis media despite appropriate antibiotic therapy. PMID- 11210877 TI - Mucosal immunity of the middle ear: analysis at the single cell level. AB - OBJECTIVE: Studies have suggested that the middle ear is a potential site of immunological regulation and that the middle ear mucosa constitutes a part of the mucosal immune system. We clarify the characteristics of the middle ear mucosa with respect to immune potential. STUDY DESIGN: We investigated lymphocyte subsets, mRNA of cytokines, and induction of antigen-specific IgA-producing cells in the middle ear mucosa in specific pathogen-free C57BL/6 mice. RESULTS: Flow cytometric analysis showed a certain amount (10%-15%) of gammadelta T cells among CD3+ T cells. P6-specific IgA-producing cells were induced by intranasal immunization with P6 together with cholera toxin. RT-PCR assay of mucosal T cells detected mRNA of Th2 type cytokines such as IL-5 and IL-10. CONCLUSION: These findings support the fact that the middle ear is potentially an effector site of the mucosal immunity. PMID- 11210878 TI - How does endotoxin trigger inflammation in otitis media with effusion? AB - OBJECTIVES: The relationship among microorganisms, endotoxin, and inflammatory mediators in otitis media with effusion (OME) was examined. STUDY DESIGN: Analysis of 152 middle ear effusions aspirated at the time of ventilation tube insertion from children with OME. METHODS: Effusion samples were cultured for pathogenic bacteria The two primary cytokines, interleukin-1beta (IL1beta) and tumor necrosis factor (TNFalpha), and the adhesion molecules, intercellular and vascular adhesion molecule (ICAM-1 and VCAM-1), were quantified using the enzyme linked immunosorbent assay (ELISA) technique. Endotoxin concentration was measured with a limulus amebocyte lysate assay, and total protein concentration was quantified using the Biorad microassay. RESULTS: The cultures of pathogenic bacteria were positive in 33 of the 152 effusions (22%), which contained more endotoxin and more of the primary cytokines than the 119 culture-negative effusions. Endotoxin and the primary cytokines were positively correlated, both in the whole material and in the sterile effusions alone. The adhesion molecules were positively correlated with each other, but not with endotoxin or the primary cytokines. CONCLUSIONS: We found a positive correlation between endotoxin and the primary cytokines TNFalpha and IL1beta in culture-positive OME effusions as well as in culture-negative ones, suggesting endotoxin-induced local production of TNFalpha and IL1beta in the middle ear. ICAM-1 and VCAM-1 were also present in the middle ear, but their concentrations were not directly correlated to endotoxin or the primary cytokines. PMID- 11210879 TI - Nitric oxide contributes to control of effusion in experimental otitis media. AB - OBJECTIVES/HYPOTHESIS: Nitric oxide (NO) is a small, short-lived free radical involved in cellular signaling and known to play a role in inflammation. It is generated on demand by the enzyme nitric oxide synthase (NOS) on arginine. We have previously found that mRNA encoding NOS is produced in the middle ear during otitis media. The role of NO was therefore explored in an experimental model of immune-mediated otitis media. STUDY DESIGN AND METHODS: Guinea pigs were systemically immunized and later challenged in the middle ear with the same antigen. One ear of each animal was challenged with antigen alone. In the opposite ear, antigen was combined with a potent inhibitor of NOS, N(G)-amino-L arginine (L-NAA). After survival for 24, 48, or 72 hours, the middle ears were evaluated for otitis media. RESULTS: Inhibition of NOS resulted in significantly increased middle ear effusion at all three time periods. This increase was blocked by the addition of excess 1-arginine, which bypasses the inhibitory effects of L-NAA. The infiltration of cells into the middle ear lumen and the hyperplasia of the middle ear mucosa were unaffected by L-NAA administration. CONCLUSIONS: The results suggest that NO is involved in regulating the permeability of the middle ear vascular, the transudation of serum into the middle ear mucosa, and/or the movement of extracellular fluid across the middle ear mucosal epithelium. PMID- 11210880 TI - Ionomeric cement in the human middle ear cavity: long-term results of 23 cases. AB - OBJECTIVES: The long-term results of the implantation of glass ionomer cement in the human mastoid and middle ear were studied. STUDY DESIGN: A prospective study of the survival of bone cement in the middle ear. METHODS: Ionocem (IONOS, Medizinische Produkte Gmbh & Co., Seefeld/Obb, Germany), a two-compound bone material that forms a stable, water-proof junction with bone, was implanted in 23 middle ears of 23 patients (13 male and 10 female patients). Closure of the dehiscence of the tegmen was performed in 7 cases, obliteration of the mastoid cavity in 10 cases, and ossicular chain reconstruction in 6 cases. RESULTS: The follow-up period was 5.1 years. Complications attributable to operation were not seen, but adverse tissue reaction with severe middle ear infection and abundant otorrhea occurred in six cases after 12 months, requiring repeat operation. In three more cases, a spontaneous extrusion of the bone cement was seen after 4 years. The bone cement was totally extruded in nine cases. The mean survival time was 28 months. CONCLUSIONS: The use of Ionocem for obliteration of the mastoid cavity or for the closure of dehiscence of the tegmen has a high risk of extrusion. Therefore, it is not the first-choice material to use for obliteration or tegmen defect closure in the middle ear. PMID- 11210881 TI - The relationship between dental overbite and eustachian tube dysfunction. AB - OBJECTIVE: The purpose of this study was to investigate the association between deep dental overbite and eustachian tube dysfunction (ETD). DESIGN: Case-control study. SETTING: Tertiary care pediatric otolaryngology outpatient clinic at the Children's Hospital, Boston, Massachusetts. PATIENTS: 105 patients between the ages of 2 and 6 years. STUDY MEASUREMENTS: Dental overbite, overjet, and occlusal relationships were measured by an observer who was unaware of ETD status. ETD was defined as having ventilation tubes in place or having the recommendation for ventilation tube placement by an attending pediatric otolaryngologist. In addition, demographic information and medical and social histories were prospectively recorded. RESULTS: In a multivariate logistic regression model, children with deep bites were 2.8 times more likely to have ETD than those without deep bites (P = .03). Other independent risk factors for ETD identified in this model were family history of otitis media (OM) and age less than 3 years. CONCLUSIONS: Children with deep dental overbites are at a significantly increased risk for developing ETD. PMID- 11210882 TI - Excision of the preauricular sinus: a comparison of two surgical techniques. AB - OBJECTIVES: To compare the long-term recurrence rate of the standard technique (simple sinectomy) and the supra-auricular approach (wide local excision) for the surgical management of preauricular sinuses. STUDY DESIGN: Retrospective cohort. METHODS: Fifty-four patients with a preauricular sinus excised between May 1986 and December 1996 were included in this study. All patients were categorized into one of two groups based on the type of surgery performed: the standard technique or the supra-auricular approach. The medical records were then reviewed and the latest information concerning the recurrence of a preauricular sinus were updated by phone interview. The recurrence rate of these two groups was statistically analyzed by the Fisher exact test. RESULTS: Forty-nine of 54 patients were successfully contacted with data updated and analyzed. The 32% recurrence rate of the standard excision (n = 25) was significantly higher than the 3.7% recurrence rate of the supraauricular approach (n = 27; two-tailed test, P = .01). CONCLUSION: The supra-auricular approach for excision of a preauricular sinus has a statistically lower recurrence rate in comparison to the standard technique. PMID- 11210883 TI - Optic nerve decompression in the comatose and conscious patients after trauma. AB - OBJECTIVE: To investigate the efficacy of early optic nerve decompression in comatose and conscious patients with indirect traumatic optic neuropathy. STUDY DESIGN: Retrospective analysis of 65 optic nerve decompressions. METHODS: The total collective of optic nerve decompressions comprised 65 patients treated within the period between February 1987 and December 1998. Thirteen of these 65 patients (average age, 32 y) were comatose and required critical care treatment, so visual acuity could not be measured. The indication for surgical decompression in all patients was based on the ophthalmological examination and the finding on computed tomography (CT) scan of a lesion inside the optic nerve canal or the orbit apex, respectively. RESULTS: In the comatose patients the time interval between trauma and surgery was 16.1+/-12.1 hours (mean +/- standard deviation). During the subsequent postoperative examinations (on average, 12.3 mo postoperatively) five patients showed a normal visual acuity (20/20), two patients a visual acuity of 20/30 and 20/50, and one a visual acuity of 20/200. Three patients (three eyes) remained amaurotic. Two patients died of the general and severe consequences of injury. The beneficial visual acuity results achieved within the group of comatose patients were equivalent to those achieved within the group of patients who were conscious during the preoperative examination. The success rate, defined as an improvement of three lines with a final visual acuity of at least 20/1000, was 57.7% versus 61.5%. CONCLUSION: The results confirm our concept of early decompression of the optic nerve, based on close interdisciplinary cooperation and the ophthalmological findings. PMID- 11210885 TI - Alternative voice after laryngectomy using a sound-producing voice prosthesis. AB - OBJECTIVE: To improve the voice quality of female laryngectomees and/or laryngectomees with a hypotonic pharyngoesophageal (PE) segment by means of a pneumatic artificial source of voice incorporated in a regular tracheoesophageal (TE) shunt valve. STUDY DESIGN: Experimental, randomized, crossover trial. METHODS: The new sound source consists of a single silicone lip, which performs an oscillatory movement driven by expired pulmonary air flowing along the outward striking lip through the TE shunt valve. A prototype of this pneumatic sound source is evaluated in vitro and in six laryngectomees. In vivo evaluation includes speech rate, maximal phonation time, perceptual voice evaluation of read aloud prose by an expert listener, speech intelligibility measurements with 12 listeners, and self-assessment by the patients. Moreover, extensive acoustical and aerodynamic in vivo registrations are performed using a newly developed data acquisition system. RESULTS: The current prototype seems beneficial in female laryngectomees with a hypotonic PE segment only. For them the sound-producing voice prosthesis improves voice quality and increases the average pitch of voice, without decreasing intelligibility or necessitating other pressure and airflow rates than regular TE shunt speech. Pitch regulation of this prosthetic voice is possible, yet limited. CONCLUSIONS: The mechanism is feasible and does not result in unacceptable airflow resistance. For this new mechanism of alaryngeal voice to become an established technique for postlaryngectomy voice restoration, a voice suitably pitched for male laryngectomees has to be generated and a large part of the melodic and dynamic range of the sound source has to be attainable within physiological airflow rates. PMID- 11210884 TI - The role of topical antibiotic prophylaxis in patients undergoing contaminated head and neck surgery with flap reconstruction. AB - OBJECTIVES/HYPOTHESIS: Patients undergoing contaminated head and neck surgery with flap reconstruction have wound infection rates of 20% to 25% with parenteral antibiotic prophylaxis. Studies suggest that perioperative antimicrobial mouthwash reduces oropharyngeal flora and may prevent wound infections. We hypothesized that the addition of topical antibiotics to a parenteral prophylactic regimen would reduce the incidence of wound infection in these high risk patients. STUDY DESIGN: We performed a randomized, prospective clinical trial. METHODS: Patients received either 1) parenteral piperacillin/tazobactam (3.375 g every 6 hours for 48 h) or 2) parenteral piperacillin/tazobactam plus topical piperacillin/tazobactam administered as a mouthwash immediately before surgery and once a day for 2 days postoperatively, with piperacillin/tazobactam added to the intraoperative irrigation solution. The wounds of all patients were evaluated daily using predefined objective criteria. RESULTS: Sixty-two patients met inclusion criteria and were enrolled in the study. The overall wound infection rate was 8.1% (95% confidence interval [CI], 2.7%-17.8%). Two of 31 patients (6.4%) who received parenteral antibiotics alone developed a wound infection compared with 3 of 31 patients (9.7%) randomly assigned to receive topical plus parenteral antibiotics. This difference was not statistically significant (P = >.05). Infection rate was not associated with flap type (rotational vs. free tissue transfer), mandibular reconstruction, age, gender, tumor site, stage, surgical duration, or blood loss. CONCLUSIONS: These results suggest that piperacillin/tazobactam is a highly effective antibiotic for prevention of wound infection in patients undergoing flap reconstruction following contaminated head and neck surgery. However, the addition of topical piperacillin/tazobactam does not appear to enhance the prophylactic benefit of parenteral antibiotics alone. PMID- 11210886 TI - Submandibular gland transfer: a new method of preventing radiation-induced xerostomia. AB - OBJECTIVE: Radiation-induced xerostomia is a significant morbidity of radiation therapy in the management of patients with head and neck cancers. We have recently reported a method of transfer of one submandibular gland to the submental space in a small pilot series of eligible surgical patients. The submental space was shielded during postoperative radiation therapy. The transferred gland continued to function after the completion of radiation therapy and none of the patients developed xerostomia. The purpose of this article is to present the technique of submandibular gland transfer in detail and to evaluate the postoperative survival and function of the transferred submandibular glands. DESIGN: Prospective clinical trial. METHODS: The submandibular gland was transferred on eligible patients as part of their surgical intervention. The patients were followed clinically, with salivary flow and radioisotope studies. RESULTS: We performed the surgical transfer of the submandibular salivary gland in 24 of 25 patients placed on the protocol. All the glands survived transfer and functioned well postoperatively as demonstrated on the salivary flow and the radioisotope studies. The surgical transfer was relatively simple and added 45 minutes to the surgical procedure. There were no complications attributed to the submandibular gland transfer. CONCLUSIONS: We have successfully demonstrated that the submandibular gland can be surgically transferred to the submental space with its function preserved. The gland seems to continue functioning even after radiation therapy with the appropriate shielding. This surgical transfer procedure has the potential to change the way we currently manage patients with head and neck cancer. PMID- 11210887 TI - Endoscopic evaluation of the infratemporal fossa. PMID- 11210888 TI - An effective, inexpensive, temporary surgical obturator following maxillectomy. PMID- 11210889 TI - Prosthetic obturation of tracheoesophageal fistula. PMID- 11210890 TI - Ventilation silicone T-shaped tube insertion. PMID- 11210891 TI - A new endoscopic surgical method for unilateral choanal atresia. PMID- 11210892 TI - Zolpidem and driving impairment. AB - Zolpidem, a non-benzodiazepine hypnotic, was identified in the blood of 29 subjects arrested for impaired driving. Zolpidem concentrations ranged from 0.05 to 1.4 mg/L (mean 0.29 mg/L, median 0.19 mg/L). In the subjects whose cases we reviewed where zolpidem was present with other drugs and/or alcohol, symptoms reported were generally those of CNS depression. Symptoms included slow movements and reactions, slow and slurred speech, poor coordination, lack of balance, flaccid muscle tone, and horizontal and vertical gaze nystagmus. In five separate cases, where zolpidem was the only drug detected (0.08-1.40 mg/L, mean 0.65 mg/L, median 0.47 mg/L), signs of impairment included slow and slurred speech, slow reflexes, disorientation, lack of balance and coordination, and "blacking out." Although no quantitative relationship between blood concentrations and degree of driving impairment is currently possible, it is reasonable to conclude that because of its specific activity as a sleep inducer, blood concentrations consistent with therapeutic doses of zolpidem have the potential to affect driving in a negative way, and that concentrations above the normal therapeutic range would further impair a person's level of consciousness and driving ability. PMID- 11210893 TI - DNA typing results from two urban subpopulations of Pakistan. AB - A population genetic characterization of the Araeen and Raajpoot ethnic subpopulations of Lahore City, Pakistan was undertaken in order to assess the utility of DNA typing for forensic purposes in Pakistani populations. One hundred unrelated individuals from each group were genotyped for four independently assorting loci: HLA DQAI, CSF1PO, TPOX, and TH01. Allele frequencies were calculated, one- and two-locus tests for association were conducted, and the samples were compared by contingency table tests and F-statistic estimation. Although there is expected to be some genetic divergence between the two groups, forensic needs may be satisfied with a single Pakistani database of DNA profiles. The present data suggest that nine independently assorting loci will be sufficient to provide estimated profile probabilities of the order of 10(-9) but a set of 13 loci, as employed in the U.S., would better compensate for the dependencies introduced by family membership and evolutionary history. PMID- 11210894 TI - The structure, frequency, and forensic application of the STR locus D16S543 in the Japanese population. AB - D16S543 is a complex STR locus consisting of five types of repeat units. The frequency distribution and genetic characteristics of this locus in Japanese were investigated using blood samples from 124 unrelated Japanese and 15 families. Alleles were detected using denatured polyacrylamide gels followed by automated analysis on an ABI 373 sequencer using Genescan software 672. Twenty-one alleles were identified, ranging in size from 281 to 489 bp. An allelic ladder containing the 21 alleles was constructed and used as a typing standard. The repeat unit arrays allowed the 21 alleles to be classified into three distinct groups, including alleles 1 to 7 in group I, alleles 8 to 14 in group II, and alleles 15 to 22 in group III. The alleles in group II were characterized by the insertion of one repeat unit of CAGG, one of AAAG, and three of AAGG, while the group III alleles differed from those of groups I and II by the insertion of a total of 32 repeat units ranging in 5 types. Within each group, the alleles differed from each other only in one 5' side tetranucleotide AAGG. The power of discrimination (Pd) and the estimated heterozygosity were calculated to be 0.989 and 0.934, respectively. Typing of this locus was successfully applied in four old forensic materials. The study presented herein demonstrates that D16S543 is a highly polymorphic and applicable locus in Japanese. PMID- 11210895 TI - Determination of drug levels in larvae of Protophormia terraenovae and Calliphora vicina (Diptera: Calliphoridae) reared on rabbit carcasses containing morphine. AB - Two species of blow flies (Diptera: Calliphoridae) were reared on tissues from rabbits administered different dosages of morphine. These species, Protophormia terraenovae and Calliphora vicina are among the first wave of insects colonizing a dead body. Two series of 3 rabbits were given dosages of 10, 20, and 40 mg/h of morphine over a 3 h period via ear artery perfusion. A morphine blood level plateau was attained after 1 h of perfusion. Two other rabbits were used as controls. Samples of tissues collected from rabbits using a coelioscopic technique were determined to have morphine concentrations similar to those encountered in human overdoses and were correlated with dosages of morphine administered. All samples from control rabbits were negative for morphine. Larvae and puparia of both species were regularly collected from each rabbit for toxicological analysis. Concentrations of morphine in larvae reared on rabbit carcasses containing morphine were significantly lower than concentrations found in the tissues. There was a decrease in concentration in morphine observed in transition from feeding 3rd instar larva to puparium. A correlation between larval concentration and tissue concentration was found only in feeding 3rd instar larvae. PMID- 11210896 TI - Natural DNA mixtures generated in fraternal twins in utero. AB - Analysis of multiple genetic loci using short tandem repeats (STR) is widely used in human identity testing because the extensive polymorphism at these loci allows for a high degree of discrimination among individuals. We recently received a forensic case that included several pieces of evidence and reference blood samples. Upon initial testing, one of the suspects had a DNA profile that included three alleles at four of the nine loci tested (vWA, FGA, TH01, and D5S818). At each locus, two of the alleles appeared to be "major" alleles with a third "minor" allele present. The profile appeared to be a mixture of two people. Contamination of this first reference sample was suspected and a second, unopened blood specimen was requested from this individual. The DNA profile from this second reference specimen was identical to that of the original specimen at each locus. One of the evidence samples also displayed an identical mixed DNA profile matching that of the reference specimens mentioned above. The relative peak heights of the two "major" and one "minor" allele remained constant in all three samples. Additional background information revealed that the suspect had not received a bone marrow transplant or blood transfusion. However, it was disclosed that this individual is a fraternal (dizygotic) twin. We hypothesize that an exchange of blood cells between the fetuses occurred in utero and that the additional alleles present in these reference samples are derived from cells contributed by his twin sibling. No additional specimens from the suspect or his twin could be obtained for confirmation, and our hypothesis remains untested. Forensic scientists should be aware of this possibility when faced with a DNA profile in which extra alleles at multiple loci are detected. PMID- 11210897 TI - A silica-based mitochondrial DNA extraction method applied to forensic hair shafts and teeth. AB - The purpose of this study is to evaluate the applicability of a nonorganic DNA extraction method for use in the analysis of environmentally compromised forensic hair shaft and tooth samples. The condition of the samples included cases of water decomposition, severe incineration, and varying stages of putrefaction. Enzymatic amplification and manual sequencing of the first segment of the mitochondrial hypervariable region were performed successfully on each of the 20 autopsied individuals. The results indicate that the silica-based extraction method produces mtDNA suitable for genetic identification from forensic samples including hair shafts and teeth. PMID- 11210898 TI - Scanning electron microscopy determination of string mozzarella cheese in gastric contents. AB - As part of a suspected homicide investigation, a sampling of the gastric contents from the victim was forwarded to the U.S. Food and Drug Administration's Forensic Chemistry Center (FCC) for analysis of specific, selected components. The victim was known to have consumed string mozzarella cheese, as a snack, less than 24 h before his disappearance and the subsequent discovery of the body. The investigation sought to confirm or dismiss speculation the victim may have been fed a meal or eaten additional food prior to his death. Analysis of the stomach contents involved examination by stereoscopic light microscopy (SLM) and isolation, processing, and analysis of suspect materials by scanning electron microscopy (SEM). Several wax-like, off-white to cream-colored objects were noted by SLM examination and removed from the gastric contents. Through a series of fixation, sectioning, drying, and coating steps, these objects were prepared for analysis by SEM. Comparison of the suspect material with laboratory control string mozzarella cheese showed excellent correlation between the analyzed samples, confirming the suspect material from the stomach contents as string mozzarella cheese. PMID- 11210899 TI - Using brain MERMER testing to detect knowledge despite efforts to conceal. AB - This experiment examined the accuracy and reliability of the memory and encoding related multifaceted electroencephalographic response (MERMER) technique for detecting information related to events subjects have experienced, despite subjects' efforts to conceal that knowledge. Information obtained through interviews was used to develop stimulus sets consisting of words and phrases presented to subjects visually by computer. Sets were composed of three types of stimuli: life experience-related (Probes), stimuli the subject was asked to memorize and respond to (Targets), and irrelevant information (Irrelevants). Each set of stimuli was tested on two individuals: (1) one individual who had participated in the event in question--and thus had the relevant information stored in his/her brain, and (2) one who had not. Six subjects were tested. Electrical brain responses to the stimuli were recorded non-invasively from the scalp and analyzed. MERMERs, (memory and encoding related multifaceted electroencephalographic responses), of which the P300 is a sub-component, were used to determine whether the subject had the relevant information stored in his brain (information present) or not (information absent), thus indicating whether or not each subject had participated in the real-life event in question. Bootstrapping was used to analyze and compare the responses to the three types of stimuli. As predicted, MERMERs were elicited by Probe stimuli only in the subjects who had participated in the investigated event, by Target stimuli in all subjects, and in no case by Irrelevant stimuli. For each of the six subjects, brain MERMER testing correctly determined whether the subject had participated in and consequently knew about the event in question (information present) or had not participated (information absent). The statistical confidence for this determination was 99.9% in five cases and 90.0% in one case. The article concludes with a discussion of areas of future research and the potential for using this new technology as an investigative tool in criminal cases. PMID- 11210900 TI - Supermarket tampering: cocaine detected in syringes and in fruit. AB - Product tampering, as detailed by the Federal Anti-Tampering Act of 1983 (1), is a felony punishable by both fine and imprisonment. The rationale for product tampering ranges from pranks and attention seeking acts to extortion, terrorism, and homicide. One such case submitted for analysis involved four medical syringes found in a supermarket and suspected of being used to tamper with various products. One of the syringes was found piercing a pear while the other three syringes were found with needles exposed in other parts of the supermarket. Microscopic analysis was used to collect residue from the syringe barrels and the pear. A multidiscipline approach involving SLM, PLM, including microchemical analysis, FTIR, and GC/MS analyses, performed on the residual liquid found in the syringe barrels and in the suspect pear, confirmed the presence of cocaine. This multidisciplinary approach is often necessary when there is a possible health risk to the public and rapid response is important. With this approach, it was quickly determined which drugs or poisons were used in this tampering. PMID- 11210901 TI - Examination of lightbulb filaments after a car crash: difficulties in interpreting the results. AB - A drunk car driver was involved in a fatal crash with a scooter at night. Examination of the lightbulbs from the vehicles revealed some mechanical and analytical incompatibilities. The laboratory's initial observations led to complementary police investigations which finally solved the first incompatibility. The different precautions taken by the technical police investigators on the crime scene finally allowed the forensic scientists to establish the functional state of the lightbulbs during the crash. PMID- 11210902 TI - Postmortem microscopic changes observed at the human head hair proximal end. AB - Only two types of human hair roots (proximal ends) derived from decomposing scalps are reported in the literature. The most common representation of the putrid root includes a postmortem dark root band in published photomicrographs. In this study, 22 cases were reviewed in which there was reliable time of death documentation from medical investigator reports. A review of these cases finds that the most common putrid hair proximal end change does not contain the postmortem root band. Four primary types of hair proximal end postmortem change were identified. This study finds no correlation of time of death with scalp hair proximal end decomposition. In addition two examples are presented that suggest that hair roots do not decompose after fresh removal from the scalp and exposure to the outside elements. PMID- 11210903 TI - Polyclonal systemic immunoblast proliferation: an unusual hematologic entity presenting as a medical examiner case. AB - A 43-year-old woman who was receiving oral antibiotics for several days for a superficial foot infection developed a persistent rash, fever, and lymphadenopathy, despite discontinuation of the antibiotic and administration of steroids for a presumed drug reaction. Hours after a subsequent visit to the emergency room for worsening symptoms, she died at home. At autopsy, there was a florid, systemic proliferation of polyclonal plasma cells and immunoblasts infiltrating nearly every organ and tissue of the body, most notably the lymph nodes and spleen. The polyclonal nature of the process was confirmed by immunofixation electrophoresis and immunohistochemistry. Cases of fatal polyclonal systemic immunoblast proliferations are extremely rare, and the trigger for such proliferations is not always known. We review the literature on this unusual entity and discuss the clinical and pathologic findings. PMID- 11210904 TI - Wounding characteristics of glaser safety ammunition: a report of three cases. AB - Handgun ammunition that contains multiple pellets (birdshot) comes in two forms. We describe here the autopsy and radiographic findings in three individuals who were fatally wounded with Glaser safety ammunition and contrast the findings to those reported in shot shell injuries. PMID- 11210905 TI - Pesticide poisoning initially suspected as a natural death. AB - A pesticide poisoning victim suspected initially as having died a natural death was autopsied. The victim was a 47-year-old male. Macroscopically, signs of acute death and, in particular, general erosion in the mucosa of the airways and esophagus were observed. In the gastric contents, which had a pungent smell and a greenish-brown color, 5.00 g/L of propanil, 1.27 g/L of carbaryl, 0.38 g/L of ethylbenzene, and 0.32 g/L of xylene were detected. In the blood (serum), 21.6 mg/L of propanil, 8.1 mg/L of carbaryl, 1.7 mg/L of ethylbenzene, and 4.0 mg/L of xylene were identified. Postmortem methemoglobinemia (45%) was recognized. The cause of death was considered to have been pesticide poisoning; propanil was probably most responsible for his death. The police considered the case to be "death with illness as the suspected cause." By performing an autopsy, however, we were able to clarify that the cause of death was pesticide poisoning. PMID- 11210906 TI - Cardiac rupture following blunt trauma. AB - A case of cardiac rupture following blunt trauma with no additional injuries is described. This can be a difficult diagnosis because of the presence of additional injuries and the lack of clinical symptoms. Here, there was a rupture of the pericardium, all chambers of the heart and the thoracic aorta. PMID- 11210907 TI - Mitochondrial DNA analysis of the presumptive remains of Jesse James. AB - We report here the results of mtDNA analysis of remains exhumed in July, 1995 from Mt. Olivet Cemetery in Kearney, Nebraska, that are thought to be those of Jesse James. The remains were poorly preserved, presumably due to wet and slightly acidic soil conditions, and insufficient DNA for analysis was obtained from two bone samples. However, two of four teeth, and two hairs recovered in 1978 from the original burial site on the James Farm, did yield reproducible mtDNA sequences. These mtDNA sequences from the teeth and hairs were all identical, suggesting that they came from the same individual; furthermore, this mtDNA sequence was identical to mtDNA sequences determined from blood samples from two maternal relatives of Jesse James. Therefore, either the remains are indeed those of Jesse James, or they are from an unrelated individual who, by chance, happens to have the same mtDNA sequence. To assess the probability that an unrelated individual would have the same sequence, we searched the forensic mtDNA database, and found that this sequence does not appear among the 2426 mtDNA sequences therein. Hence, the mtDNA analysis supports the identification of the exhumed remains from Mt. Olivet Cemetery as those of Jesse James. PMID- 11210909 TI - Uruguayan population data for eight STR loci (using the PowerPlex 1.2 kit). PMID- 11210908 TI - Allele frequency for D1S80 locus in Tamil population (South India). PMID- 11210910 TI - Allele frequencies and haplotypes of ten Y-specific STRs in the Japanese population. PMID- 11210911 TI - Population data on eight STR loci in Buenos Aires (Argentina). PMID- 11210912 TI - Population data for nine fluorescent based STR loci among four important tribal populations of India. PMID- 11210913 TI - Allele frequencies for four STR loci (D16S539, TH01, TPOX, and CSF1PO) in African American and Caucasian populations from Marion County, Indiana, USA. PMID- 11210914 TI - Distribution of alleles D16S539, D7S820, D13S317 in a southern Italian population sample. PMID- 11210915 TI - Allele frequency distributions for D1S1656, D8S1132, D10S2325, D18S51, and D21S11 loci in a north Italy population. PMID- 11210916 TI - A population-genetic study of the DYS385 haplotypes in two Spanish populations and the African immigrant population in Spain. PMID- 11210917 TI - The AICEF/GITAD: Latin American Academy of Criminalistics and Forensic Studies. PMID- 11210918 TI - Misinterpretation of a urinary 6-monoacetyl morphine concentration. PMID- 11210919 TI - Detection of deviations from genetic equilibrium--a commentary on Budowle B, Moretti TR, Baumstark AL, Defenbaugh DA, Keys KM. Population data on the thirteen CODIS core short tandem repeat loci in African Americans, US Caucasians, Hispanics, Bahamians, Jamaicans, and Trinidadians. J Forensic Sci 1999;44:1277 86. PMID- 11210920 TI - HPLC analysis of ballpoint pen inks stored at different light conditions. AB - A method for comparison of ink entries on documents stored in different light conditions is presented. Various blue inks were exposed to light, both daylight and artificial light from fluorescent tubes. Inks were then extracted from the document and analyzed by HPLC (high performance liquid chromatography). Significant changes in composition were noted on exposure to light. These changes were followed by using ternary diagrams constructed for dyes generally present in blue-colored inks--Crystal Violet, Methyl Violet, and Tetramethyl Para Rosaniline. Also, the amount of the various compounds formed by decomposition of these dyes on exposure to light was measured and employed for comparison of inks. An example of the use of the proposed method in casework is given. PMID- 11210921 TI - Discrimination of 1990s original automotive paint systems: a collaborative study of black nonmetallic base coat/clear coat finishes using infrared spectroscopy. AB - The 1990s saw the introduction of significantly new types of paint binder chemistries into the automotive finish coat market. Considering the pronounced changes in the binders that can now be found in automotive paints and their potential use in a wide variety of finishes worldwide, the Paint Subgroup of the Scientific Working Group for Materials (SWGMAT) initiated a validation study to investigate the ability of commonly accepted methods of forensic paint examination to differentiate between these newer types of paints. Nine automotive paint systems typical of original equipment applications were acquired from General Motors Corporation in 1992. They consisted of steel panels coated with typical electrocoat primers and/or primer surfacers followed by a black nonmetallic base coat and clear coat. The primary purpose of this study was to evaluate the discrimination power of common forensic techniques when applied to the newer generation original automotive finishes. The second purpose was to evaluate interlaboratory reproducibility of automotive paint spectra collected on a variety of Fourier transform infrared (FT-IR) spectrometers and accessories normally used for forensic paint examinations. The results demonstrate that infrared spectroscopy is an effective tool for discriminating between the major automotive paint manufacturers' formulation types which are currently used in original finishes. Furthermore, and equally important, the results illustrate that the mid-infrared spectra of these finishes are generally quite reproducible even when comparing data from different laboratories, commercial FT-IR instruments, and accessories in a "real world," mostly uncontrolled, environment. PMID- 11210922 TI - Diversity and heterogeneity in mitochondrial DNA of North American populations. AB - Variation in the mitochondrial DNA (mtDNA) control region as detected by sequence specific oligonucleotide (SSO) probes is described for 2282 individuals from African-American, European-American, and Hispanic subpopulations from five broadly defined regions of North America (Northeast, Southeast, Central, Northwest, Southwest). Population diversity estimates were uniformly high for all subpopulations and for each major ethnic group. Only the Pennsylvania Hispanic group was remarkable with respect to its mitochondrial DNA types, having both six low frequency population specific types (ranging from 1.2-8.6%) and three high frequency shared types (10-20% each). There was no statistically significant subpopulation heterogeneity present within any of the three major groups at either the subpopulation level or the regional level (p > 0.01). However, statistically significant heterogeneity was measured when comparing the three major groups to each other, with the variance component attributable to this large division accounting for 18.60% of the total variance (p < 0.001). Overall mtDNA is a satisfactory forensic typing locus within broadly defined African American, European-American, and Hispanic groups from North America, based on the high diversity estimates and absence of heterogeneity, as characterized by SSO typing. PMID- 11210923 TI - Quality assurance testing of an explosive trace analysis laboratory. AB - During 1989, the Forensic Explosives Laboratory (FEL) established a weekly quality assurance testing regime in its explosives trace analysis laboratory. The purpose of the regime is to prevent the accumulation of explosives traces within the laboratory at levels which could, if other precautions failed, result in the contamination of samples and controls. This paper describes the regime and summarizes the results from approximately eight years of tests. Lessons learned and improvements made over the period are also discussed. PMID- 11210924 TI - Investigating the effect of changing ammunition on the composition of organic additives in gunshot residue (OGSR). AB - The measurement of the organic additives in smokeless gunpowder is an attractive approach for the detection of handgun use because it provides compositional information that can help associate residues and unfired gunpowder. We investigate several factors that will be required to advance the characterization of organic gunshot residue (OGSR) as a useful forensic tool, including evaluating residue contamination from previously fired ammunition, particle-to-particle compositional variability, and compositional features resulting from the type of firing primer used. Using ammunition loaded with known smokeless powders containing different stabilizers, a sequence of shots was fired from a .357 magnum revolver, and the muzzle exit residues were collected. Compositional analysis of the residues, both in bulk and as single particles, showed only a trace of the previously fired powder in the first shot and none in subsequent shots. In an additional experiment testing conventional leaded and the new lead free firing primers, the OGSR composition was found not to depend on the primer type. PMID- 11210925 TI - Detection limits for GC/MS analysis of organic explosives. AB - Method detection limits are determined and compared for analysis of liquid injections of organic explosives and related compounds by gas chromatography-mass spectroscopy utilizing electron impact (EI), negative ion chemical ionization (NICI), and positive ion chemical ionization (PICI) detection methods. Detection limits were rigorously determined for a series of dinitrotoluenes, trinitrotoluene, two nitroester explosives, and one nitramine explosive. The detection limits are lower by NICI than by EI or PICI for all explosives examined, with the exception of RDX. The lowest detection limit for RDX was achieved in the PICI ionization mode. Judicious choice of the appropriate ionization mode can enhance selectivity and significantly lower detection limits. Major ions are reported for each analyte in EI, PICI, and NICI detection modes. PMID- 11210926 TI - Speaker identification utilizing noncontemporary speech. AB - The noncontemporariness of speech is important to both of the two general approaches to speaker identification. Ear-witness identification is one of them; in that instance, the time at which the identification is made is noncontemporary. A substantial amount of research has been carried out on this relationship and it now is well established that an auditor's memory for a voice decays sharply over time. It is the second approach to speaker identification which is of present interest. In this case, samples of a speaker's utterances are obtained at different points in time. For example, a threat call will be recorded and then sometime later (often very much later), a suspect' s exemplar recording will be obtained. In this instance, it is the speech samples that are noncontemporary and they are the materials that are subjected to some form of speaker identification. Prevailing opinion is that noncontemporary speech itself poses just as difficult a challenge to the identification process as does the listener's memory decay in earwitness identification. Accordingly, series of aural-perceptual speaker identification projects were carried out on noncontemporary speech: first, two with latencies of 4 and 8 weeks followed by 4 and 32 weeks plus two more with the pairs separated by 6 and 20 years. Mean correct noncontemporary identification initially dropped to 75-80% at week 4 and this general level was sustained for up to six years. It was only after 20 years had elapsed that a significant drop (to 33%) was noted. It can be concluded that a listener's competency in identifying noncontemporary speech samples will show only modest decay over rather substantial periods of time and, hence, this factor should have only a minimal negative effect on the speaker identification process. PMID- 11210927 TI - Production of intoxication states by actors--acoustic and temporal characteristics. AB - This paper is the second of a series; the first has been published (J Forensic Sci, 1998;43:1153-62). The goal in the initial pair of experiments was to determine if speakers (actors) could effectively mimic the speech of intoxicated individuals and also volitionally reduce the degradation to their speech that resulted from severe inebriation. To this end, two highly controlled experiments involving 12 actor-speakers were carried out. It was found that, even when sober, nearly all of them were judged drunker (when pretending) than when they actually were severely intoxicated. In the second experiment, they tried to sound sober when highly intoxicated; here most were judged less inebriated than they were. The goal of this second paper is to identify some of the speech characteristics that allowed the subjects to achieve the cited illusions. The focus here is on four paralinguistic factors: fundamental frequency (F0), speaking rate, vocal intensity, and nonfluency level. For the simulation of intoxication study, it was found that F0 was raised along with increased intoxication but raised even more when this state was feigned. A slowing of speaking rate was associated with increasing intoxication, but this shift also was greater when the speaker simulated intoxication. The most striking contrast was found for the nonfluencies; they were doubled for actual intoxication, but quadrupled when intoxication was simulated. On the other hand, the shifts exhibited by the subjects when they attempted to sound sober were not as clear cut. Indeed, no systematic relationships were found here for either F0 or vocal intensity. Both speaking rate and the number of nonfluencies shifted appropriately, but these changes were not statistically significant. In sum, discernable suprasegmental relationships occurred for both studies (but especially the first); further, it is predicted that useful cues also will be found embedded in the segmentals (the sounds of speech). PMID- 11210928 TI - The design and assessment of mock mass disasters for dental personnel. AB - Mass disasters represent a significant challenge for dental personnel who are frequently called upon to provide identifications. Recently-published materials have highlighted the need to prepare such groups for the disaster challenge and to report inadequacies in existing preparation methods with an emphasis on team integration, organization, and the psychological and emotional effects of such work. Many studies have retrospectively reported errors that have been made in disaster situations, but few have addressed the issues proactively. In an effort to provide a prepared team of dental members, a mock disaster exercise (Operation: DENT-ID) is conducted annually in Vancouver, Canada. The present study analyzes the effectiveness of this exercise in relation to team organization, assessment of preparedness, and the emotional and psychological issues. An index of preparedness is developed and described. This index, in the form of a questionnaire, can be given to participants in mock disasters to assess the effectiveness of such exercises. While the focus of this paper is on the assessment of dental personnel, the indices and methods used can be applied to any group working within the disaster team. Results indicate that the increase in preparedness as a result of the exercise was highly significant. PMID- 11210929 TI - An investigation of the psychological characteristics of stalkers: empathy, problem-solving, attachment and borderline personality features. AB - This study examined the psychological characteristics of a sample of self reported stalkers in comparison with a control group, on measures of empathy, problem-solving skills, attachment, and borderline personality features. Stalkers were identified by their endorsement of specific behavioral items, consistent with a widely adopted definition of stalking, denoting behaviors that: (a) are repeatedly directed toward an identified target; (b) are intrusive and unwanted; and (c) evoke fear in the victim. Stalkers scored significantly higher than controls on measures of insecure attachment and borderline personality features, suggesting that the stalking group demonstrates a general pattern of inadequate interpersonal attachment, has limited abilities to form and maintain appropriate relationships, is emotionally labile and unstable, and experiences ambivalence regarding their interpersonal relationships. Treatment implications are discussed herein. PMID- 11210930 TI - Demonstration and interpretation of bridging vein ruptures in cases of infantile subdural bleedings. AB - Report of two cases of lethal infantile subdural bleedings (SDB). Bridging vein (BV) ruptures were directly proven as the source of the (minimal) SDB by a postmortem X-ray. In the controversial discussion concerning the causes of infantile SDB, proof of the occurrence of several BV ruptures is seen as an important sign of a trauma of significant degree. Although infantile SDB undoubtedly can result from accidental as well as intentional injuries, and therefore, the SDB itself does not allow far-reaching conclusions as to the cause of injury, the presence of several BV ruptures combined with an SDB of insignificant volume, in an infant dead or in a deep coma on clinical presentation, is not compatible with the supposition of a minor fall as the cause. We have not observed such findings as the result of a minor accidental event for more than 15 years. PMID- 11210931 TI - Continuous quality improvement as a management concept for death investigation systems. AB - Continuous quality improvement (CQI) represents a management technique where the basic approach to managing quality consists of setting a standard for a work process, measuring variation in the work process in relation to the standard, and then implementing programs to decrease variation and improve end results. Everyone providing a service becomes involved both in understanding how quality is measured and in discussing how to improve quality. A team approach is adopted and instead of focusing on poor quality outcomes and how to avoid them, the team becomes involved in setting continuously improving standards for better performance and in finding ways to meet those standards. The objective is to meet or exceed consumer or user expectations. Relevant related concepts such as survey research, needs determination and outcomes analysis, and the importance of a mission statement are discussed using a medical examiner system as an example. PMID- 11210932 TI - Intratracheal gas analysis for volatile substances by gas chromatography/mass spectrometry--application to forensic autopsies. AB - Intratracheal gas analysis was carried out by gas chromatography/mass spectrometry (GC/MS) in 20 burned body cases (13 males and 7 females). Volatile aromatic and aliphatic hydrocarbons were detected by GC/MS using a GS-Q column with the intratracheal gas as well as the blood in 19 cases. The characteristic patterns of mass chromatograms for gasoline, kerosene (gas oil), and liquid petroleum gas could be differentiated from each other using the intratracheal gas. The burned body in one case showed no presence of volatile substances in the intratracheal gas, nor intratracheal soot, although high concentrations (1 microg/g and more) of volatile substances were detected on the clothes. The victim also had normal CO-Hb concentrations (0.1 to 0.2%) in the heart blood. The results of intratracheal gas analysis were consistent with signs of the vital reaction. In conclusion, intratracheal gas analysis provides a supportive method for diagnosing the cause of death in burned bodies, and yields for at least 48 hours valuable information on volatile hydrocarbons (being detected in deliberate or accidental fire cases) to which the body had been exposed just before death. PMID- 11210933 TI - Characterization of the ecdysteroid UDP-glucosyltransferase (egt) gene of Anticarsia gemmatalis nucleopolyhedrovirus. AB - The Anticarsia gemmatalis nucelopolyhedrovirus (AgMNPV) egt gene was cloned, sequenced and its expression characterized by RT-PCR and western blot analysis. Sequence analysis of the gene indicated the presence of an open reading frame (ORF) of 1482 nucleotides, which codes for a polypeptide of 494 amino acids. ATATA box and a conserved regulatory sequence (CATT) found in other baculovirus early genes were present in the promoter region of the egt gene. A poly-A consensus sequence was present in the 3' untranslated region (3'-UTR) of the gene. Homology comparisons showed that the EGT protein of AgMNPV is most closely related (95.9% amino acid sequence identity) to the EGT from the Choristoneura fumiferana DEF nucleopolyhedrovirus (CfDEF). Transcriptional analysis of the AgMNPV egt gene showed that egt-specific transcripts can be detected both early and late in infection. The EGT protein was detected, by western blot analysis, in the intra- (from 12 to 48 h post-infection) and extra-cellular (from 12 to 96 h post-infection) fractions of infected insect cells. The AgMNPV Bgl II-F fragment, which has homology to the AcMNPV ie-1 gene, was cloned and used to cotransfect SF21 cells with the cloned AgMNPV egt gene. EGT activity was observed, suggesting that AgMNPV ie-1 can transactivate egt expression. PMID- 11210935 TI - Sequence analysis of the RNA polymerase gene of foot-and-mouth disease virus serotype Asia1. AB - The complete nucleotide (nt.) sequence of the RNA polymerase (3D) gene and 81 nt. in the 3'-untranslated region of foot-and-mouth disease virus (FMDV) serotype Asial (IND63/72) was determined and compared with the sequence of other FMDV serotypes. The 3D genomic region was 1410 nt. long encoding 470 amino acids with an inframe stop codon (TAA) at nt. position 1411-1413. The deduced amino acid sequence of the protein showed 8 conserved motifs as reported in other picornaviruses, 2 of which are 100% identical across the serotypes. Antigenic regions in the polymerase protein were predicted and found to be located at the N terminus of the protein. The phylogenetic analysis showed that the FMD viruses were segregated into different clusters based on geographical origin; the Asia1 virus did not cluster tightly with any of the geographical groups. PMID- 11210934 TI - Nucleotide sequence and transcriptional analysis of a putative basic DNA-binding protein of Helicoverpa armigera nucleopolyhedrovirus. AB - A putative basic DNA-binding protein (BDBP) gene was identified in the fragment EcoRI-K of the Helicoverpa armigera single-nucleocapsid nucleopolyhedrovirus (HearNPV) genome. The ORF is 330 nucleotides long encoding a basic protein of 109 amino acids with a molecular mass of 11.6 kDa. It is the first BDBP identified in single nucleocapsid NPVs and a homologue of Autographa californica MNPV (AcMNPV) P6.9. A consensus late transcription motif, ATAAG, was found at 57 nt upstream of the translational start codon and a polyadenylation signal was observed at 172 nt downstream of the stop codon. A major transcript of 620 nt was first observed in HearNPV-infected Hz2e5 cells 16 h post infection. Primer extension analysis revealed that this transcript initiated from the first residue of the consensus ATAAG late transcription start motif. Comparison with other baculoviral BDBPs showed that they all contained two conserved cAMP- and cGMP-dependent protein kinase phosphorylation motifs, R-R-R-S. The HearNPV P6.9 homologue is the longest BDBP found so far in baculoviruses. PMID- 11210936 TI - Molluscum contagiosum virus expresses late genes in primary human fibroblasts but does not produce infectious progeny. AB - Molluscum contagiosum virus (MCV), a member of the family Poxviridae, can be isolated from skin-lesion material of patients with molluscum contagiosum infection. MCV replicates efficiently in human keratinocytes in vivo but viral replication has not been observed in vitro in cell or tissue culture systems. We investigated a variety of established cell lines for productive MCV infection and found that: (i) MCV induces a typical cytopathogenic effect (CPE) only in human primary fibroblast cells (MRC5 ATCC-CCL 171 and HEPM ATCC-CRL 1486) but not in permanent eucaryotic cell lines of human or simian origin; (ii) UV irradiated MCV virions and heat inactivated virions do not induce a CPE; (iii) decreasing amounts of MCV viral DNA are detectable in infected human embryonic fibroblasts for at least 14 days post infection (p.i.); (iv) MCV early mRNAs are detectable by RT-PCR between one and two hours p.i. and remain detectable upon passaging of the infected cells; (iv) transcripts of viral late genes (mc095L and mc106L) are detectable by RT-PCR from day 5 p.i.; (v) MCV viral antigens can be detected on the surface of infected cells using human and rabbit polyclonal antisera against MCV from 24 h p.i.; (vi) a CPE can not be observed if cell free supernatants or homogenizates of MCV infected cells are used to try passage of the virus onto uninfected human embryonic fibroblasts, indicating that infectious viral progeny is not produced. This is the first report demonstrating long time persistence of MCV viral DNA and expression of late proteins in an in vitro cell culture system. PMID- 11210937 TI - Identification of a strong promoter of bacteriophage MB78 that interacts with a host coded factor and regulates the expression of a structural protein. AB - A strong promoter of bacteriophage MB78 which controls the expression of a small structural protein of the phage has been identified and characterized. Analysis of its nucloetide sequence upstream of the translational start site revealed the presence of conserved -10 (TAATAT) and -35 (TTCTCCT) regions. It was observed that transcription initiates with thymidine residue, 86 nt upstream of the translational start site. Transcription seems to undergo alternate up and down regulation. This promoter is efficiently recognized by sigma 70 RNA polymerase and a host factor also binds to it. Binding of RNA polymerase is independent of binding of the host factor. PMID- 11210938 TI - Conserved and non-conserved regions in the Sendai virus genome: evolution of a gene possessing overlapping reading frames. AB - We have sequenced the entire genome of a virulent field isolate of Sendai virus, the Hamamatsu strain, and compared the sequence with that of a distant related strain, the Z strain. Calculation of synonymous and non-synonymous (amino acid changing) nucleotide substitutions revealed regions where changes were permissive and non-permissive, and the experimentally determined functional region were found to be conserved, showing that important regions for function were conserved during evolution. In the cistron-overlapping regions in the P gene, one reading frame was conserved, whereas the other overlapping frame was flexible. The priority of one frame could be a strategy for evolution of an overlapping gene of RNA viruses. We found that the carboxyl two thirds of the C protein was conserved over the amino-terminal one third, possessing priority to the overlapping P polypeptide. This suggests that the carboxyl two thirds of the C protein have a functional importance. We also found a highly variable region between the L coding frame and the 5' trailer sequence. The relevance of these findings to actual viral replication should be clarified in the future. PMID- 11210940 TI - Phylogenetic analysis of hop and grapevine isolates of hop stunt viroid supports a grapevine origin for hop stunt disease. AB - We have examined sequence variability among nine isolates of hop stunt viroid (HSVd) collected from hop gardens in Tohoku district in Japan, the only area in the world where hop stunt disease is endemic. Six different consensus and one consensus sequences as well as 12 sequence variants were detected in the nine HSVd-hop isolates, which suggested the sequence of HSVd-hop was remarkably variable. A neighbor-joining analysis was carried out on the new HSVd-hop sequences together with 44 previously described variants of HSVd isolated from hop and other species. All the HSVd-hop sequences recovered from hops cultivated in the Tohoku district of Japan as well as the type isolate and two Korean isolates form a cluster with the HSVd-g subtype 1 commonly recovered from grapevine. This close relationship between HSVd-hop and -grapevine isolates strongly supports the grapevine origin for hop stunt disease. PMID- 11210939 TI - Antigenic and molecular analyses reveal that the equine rotavirus strain H-1 is closely related to porcine, but not equine, rotaviruses: interspecies transmission from pigs to horses? AB - We have sequenced the genes encoding the inner capsid protein VP6 and the outer capsid glycoprotein VP7 of the subgroup (SG) I equine rotavirus strain H-1 (P9[7], G5). The VP6 and VP7 proteins of the equine rotavirus strain H-1 shared a high degree of sequence and deduced amino acid identity with SG I porcine strains and serotype G5 porcine strains, respectively. Previous sequence analyses of the genes encoding the outer capsid spike protein VP4 and the nonstructural proteins NSP1 and NSP4 of equine H-1 strain also revealed a high degree of sequence and deduced amino acid homology with the prototype porcine rotavirus strain OSU (P9[7], G5). We have also confirmed and extended the VP4 and VP7 antigenic relatedness of equine rotavirus strain H-1 to porcine strains of P9[7] and G5 serotype specificities isolated in the United States, Venezuela, Argentina, and Australia based on cross-neutralization studies. In addition, the pathogenicity of tissue culture-adapted equine H-1, H-2, FI-14, FI-23, and L338, and porcine OSU rotavirus strains was compared in the neonatal mouse model. The 50% diarrhea dose (DD50) of equine H-1 was similar to that of porcine OSU and equine H-2 and L338 strains, while the DD50 of equine H-2 was > or = 50 or 315-fold lower than those of equine FI-14 or FI-23, respectively. Our sequence comparison of NSP4 of the rotavirus strains tested potentially identified amino acid residue 136, within the variable region spanning amino acids 130 to 141, as playing a role in virulence. Taken together, there is strong support to suggest that the equine rotavirus strain H-1 may represent an example of interspecies transmission from pigs to horses. PMID- 11210941 TI - Characterization of peptide substrates and viral enzyme that affect the cleavage site specificity of the human spumaretrovirus proteinase. AB - Oligopeptides that correspond to proteolytic cleavage site junctions of the native Gag and Pol proteins are specifically cleaved by retroviral aspartate proteases (PRs). The role of the flap subdomain of the PR of the human spumaretrovirus (HSRV) and of substrate peptides in cleavage site specificity was analyzed by site-directed mutagenesis. Native and mutant peptides were subjected to proteolysis by the authentic and mutated recombinant viral enzyme. The results reveal that Glu residue 54 of the HSRV PR is an essential specificity determinant for proteolytic processing of the structural proteins. Peptides that represent in vivo cleavage sites were susceptible to proteolysis by the recombinant HSRV PR, but one peptide located at the junction between the PR and reverse transcriptase domains was completely resistant to cleavage. Thus the data indicate that a proteolytic cleavage between these domains does not occur in vivo. Naturally occurring and mutant forms of the cleavage-resistant peptide were therefore analyzed by circular dichroism to determine if differences existed in the secondary structures of the peptides that did or did not serve as substrates. The data show that differences in the secondary structure of the native and mutant peptides analyzed does not seem to play a crucial role for cleavage site specificity in HSRV PR. Instead highly conserved hydrophobic residues at distinct positions of the HSRV cleavage site junctions contribute to the specificity observed as reported for HIV-1 PR. PMID- 11210943 TI - Spike gene analysis of the DE072 strain of infectious bronchitis virus: origin and evolution. AB - The entire S2 gene of the DE072 strain of infectious bronchitis virus (IBV) was sequenced. The nucleotide and amino acid sequence was most similar to the D1466 strain and was 84.8% and 89.9% identity, respectively. The nucleotide and amino acid sequence similarity among the DE072 strain and other IBV strains was less than 71.9% and 76.6%, respectively. Phylogenetic analysis, based on both nucleotide and amino acid sequence, showed that IBV isolates were divided into two distinct groups. The DE072 strain clustered only with the D1466 strain, and all of the other strains were distinct from those two viruses. Further the nucleotide sequence analysis of the entire spike glycoprotein gene of the DE072 strain demonstrated that most of the gene contained a D1466-like sequence, and five putative cross-over sites were identified. Based on cross-over site, phylogenetic trees were constructed for different regions of the spike gene, and a difference in topology between these trees was observed. Considering the difference in S2 gene sequence identity and tree topology, we assume that DE072 and D1466 viruses share a different origin from other isolates of IBV. Furthermore, entire spike gene analysis indicates that the DE072 strain has undergone recombination event as well as extensive antigenic variation. PMID- 11210942 TI - Expression of immunogenic Puumala virus nucleocapsid protein in transgenic tobacco and potato plants. AB - Transgenic plants, expressing recombinant proteins, are suitable alternatives for the production of relevant immunogens. In the present study, the expression of Puumala virus nucleocapsid protein in tobacco and potato plants (Nicotiana tabacum and Solanum tuberosum) and its immunogenicity was investigated. After infection of leaf discs of SR1 tobacco and tuber discs of potato cv. "Desiree" with the Agrobacterium strain LBA4404 (pAL4404, pBinAR-PUU-S) containing the 1302 bp cDNA sequence of S-RNA segment of a Puumala virus, transgenic tobacco and potato plants expressed the Puumala virus nucleocapsid protein under control of the cauliflower 35S promoter. The recombinant proteins were found to be identical to the authentic Puumala virus nucleocapsid protein as analyzed by immunoblotting. Expression of the nucleocapsid protein was investigated over four plant generations (P to F4) and found to be stable (1 ng/3 microg dried leaf tissue). Transgenic tobacco plants were smaller compared to controls. The transformed potato plants were morphologically similar to control plants and produced tubers as the control potatoes. The S-antigen was expressed at a level of 1 ng protein/5 microg and 1 ng protein/4 microg dried leaf and root tissues, respectively, and remained stable in the first generation of vegetatively propagated potato plants. The immunogenicity of the Puumala virus nucleocapsid protein expressed in Nicotiana tabacum and Solanum tuberosum was investigated in New Zealand white rabbits. They were immunized with leaf extracts from transgenic tobacco and potato plants, and the serum recognized Puumala virus nucleocapsid protein. Transgenic plants expressing hantaviral proteins can thus be used for the development of cost-effective diagnostic systems and for alternative vaccination strategies. PMID- 11210944 TI - The hamster polyomavirus--a brief review of recent knowledge. AB - The hamster polyomavirus (HaPV) was first described in 1967 as a virus associated with skin epithelioma of the Syrian hamster. The tumors appear spontaneously in a hamster colony bred in Berlin-Buch (HaB). Virus particles isolated from skin epitheliomas cause lymphoma and leukemia when injected into newborn hamsters from a distinct colony bred in Potsdam, Germany (HaP). The viral genome has been totally sequenced and the overall genetic organization establishes HaPV as a member of the polyomaviruses. HaPV is a second example of an middle T (MT) antigen encoding polyomavirus and nucleotide sequence homologies designates the mouse polyomavirus (Py) as the closest relative. Lymphomas induced by HaPV in HaP hamsters do not contain virus particles but instead accumulate different amounts of nonrandomly deleted free and/or integrated viral genomes. Transgenic mice produced by microinjection of HaPV DNA into the pronucleus of fertilized eggs of Gat: NMRI mice developed both, epitheliomas and lymphomas. Both tumor types contain extrachromosomal DNA. HaPV DNA was found to replicate in hamster lymphoid and fibroblast cell lines. Fully reproductive cycles could be detected only in GD36 lymphoblastic leukemia cells. HaPV carries the full transforming properties of a polyomavirus in vitro. Immortalization of primary rat cells is essentially carried out by the HaPV large T (LT) antigen and coexpression of HaPV MT and HaPV small T (ST) antigen is required for full transformation of rat fibroblasts. The preferential binding of HaPV MT to c-Fyn, a Src family kinase, has been proposed as a mechanism leading to lymphoid malignancies. Heterologous expression of HaPV VP1 allowed the formation of virus like particles (VLPs) resembling HaPV particles. The high flexibility of HaPV-VP1 for insertion of foreign peptides offers a broad range of potential applications, especially in vaccine development. PMID- 11210945 TI - Interosseous membrane anatomy and functional mechanics. AB - Longitudinal forearm stability is maintained through the interaction of several anatomic structures. One such structure, the interosseous membrane, is a fibrous tissue with an oblique orientation from the radius to the ulna. The membrane maintains the interosseous space between the radius and ulna through forearm rotation and actively transfers forces from the radius to the ulna. The interosseous membrane's unique functional capabilities result from its anatomic and histologic organization, which produces a stiff structure with elastic properties capable of maintaining large loads. The interosseous membrane's load transferring ability reduces the forces placed on the radiocapitellar articulation, thereby protecting this joint. However, large chronic loading results in attenuation of the membrane fibers, thereby reducing longitudinal stability. Large sustained loads occur after radial head resection with concurrent interosseous membrane tears, resulting in the proximal migration of the radius and disruption of the distal radioulnar joint. Ultimately, the treatment option for severe membrane disruption combined with proximal migration of the radius is the creation of a single bone forearm. PMID- 11210946 TI - The collateral ligaments of the elbow: anatomy and clinical correlation. AB - Stability of the elbow is provided by the congruous nature of the bony articulations and the medial and lateral collateral ligament complexes. The medial ligament provides additional support to valgus stress. The lateral ligament prevents rotational instability between the distal humerus and the proximal radius and ulna. Collateral ligament insufficiency typically is posttraumatic and can occur on either side of the joint. An understanding of the normal anatomy is required to make the correct diagnosis and complete a successful surgical reconstruction. PMID- 11210947 TI - Osseous anatomy of the scapula. AB - Detailed anatomy and morphometry of the scapula were obtained to provide information for surgical procedures such as hardware fixation, drill hole placement, arthroscopic portal placement, and prosthetic positioning. Twenty-six measurements were made in 15 pairs of scapulas from cadavers. The average length of the scapulas from the superior to the inferior angle was 155 +/- 16 mm (mean +/- standard deviation). The thickness of the medial border 1 cm from the edge was 4 +/- 1 mm. The superior border was sharp and thin, and the suprascapular notch was present as a foramen in two scapulas. The distance from the base of the suprascapular notch to the superior rim of the glenoid was 32 +/- 3 mm. The length of the spine from the medial edge of the scapula to the lateral edge of the acromion was 134 +/- 12 mm. The anteroposterior width of the spine at 1 and 4 cm from the medial edge was 7 +/- 1 and 18 +/- 3 mm, respectively; the width at the lateral edge (spinoglenoid notch) was 46 +/- 6 mm. The acromion measured 48 +/- 5 mm x 22 +/- 4 mm and was 9 +/- 1 mm thick. The acromial shape was flat in 23%, curved in 63%, and hooked in 14% of scapulas. The distance from the glenoid to the acromion was 16 +/- 2 mm. The glenoid dimensions were 29 +/- 3 mm (anteroposterior) x 36 +/- 4 mm (superoinferior) and faced posterior by 8 +/- 4 degrees. Anteroposterior thickness of the head of the scapula 1 cm from the surface was 22 +/- 4 mm. The thickness of the coracoid was 11 +/- 1 mm. The average length of the coracoacromial ligament was 27 +/- 5 mm. Scapulas from male cadavers were significantly larger than scapulas from female cadavers in 19 measurements. PMID- 11210948 TI - Clinical significance of skeletal muscle architecture. AB - Skeletal muscle architecture is one of the most important properties that determines a muscle's force and excursion capability. In the current review, basic architectural terms first are reviewed and then specific examples relevant to upper extremity anatomy are presented. Specific examples of anatomic considerations required for surgical reconstruction after radial nerve palsy also are detailed. Together, these data show not only the wide variety of architectural designs in human muscles, but the importance of considering architectural design when making surgical decisions. PMID- 11210949 TI - Biomechanical analysis of the brachioradialis as a donor in tendon transfer. AB - Anatomic and biomechanical properties of the passive brachioradialis muscle were investigated to understand the limited excursion of this muscle seen during tendon transfer surgery. First, architectural measurements were performed on three fiber bundles obtained from four regions of the brachioradialis (10 specimens) chosen to represent the range of muscle fiber lengths across the brachioradialis. Next, in separate specimens (eight specimens), passive excursion was measured by securing the distal tendon stump to a servomotor. A constant load of 4.9 N was applied to the tendon, while the distal tendon was released from the surrounding tissue in 3-cm increments. Within the four regions studied, muscle fiber length varied significantly from 104.2 +/- 6.2 mm to 179.8 +/- 6.1 mm. As the brachioradialis was released, an average of 3 mm of mobility was obtained for each interval whereas for the succeeding three intervals, an average of 5.3 mm of mobility was obtained. This resulted in 22.2 +/- 2.3 mm of mobility when each specimen was fully released. These data show that there is no intrinsic muscle fiber length limitation to excursion, but that excursion is limited by other intermuscular connections to adjacent connective tissue and other muscles. PMID- 11210950 TI - Magnetic resonance imaging of the upper extremity: advances in technique and application. AB - Vast advances in technology have taken place in the field of radiology led by the introduction of magnetic resonance imaging. The added advantages of exquisite soft tissue contrast and multiplanar imaging capabilities have revolutionized the understanding of complex anatomic relationships and diagnoses. The current authors will focus on the introduction of new advances in magnetic resonance imaging of the upper extremity that may prove helpful in the diagnosis and treatment of upper extremity abnormalities. PMID- 11210951 TI - Wear-through of a modular polyethylene liner: four case reports. AB - Four patients in whom the S-ROM Total Hip System Polydial polyethylene liner was used illustrate the importance of, and difficulties in, detecting polyethylene wear-through before a complete acetabular revision is necessary. The patients in these cases had full thickness polyethylene wear-through 11 or more years after total hip arthroplasties. Dorr and Livermore wear measurements from radiographs of the patients underestimated the actual wear and did not indicate wear-through. Because excessive head penetration was not evident radiographically with the S ROM components, the cases showed the necessity of using additional measures to diagnose wear-through, particularly with these components. Repeat radiographs at a higher kilovoltage were used to better visualize the outline of the femoral head, and hip aspiration was used to diagnose metallosis. These cases also showed the importance of yearly followup evaluations, especially 10 or more years after surgery for patients with the S-ROM Polydial locking mechanism. PMID- 11210952 TI - Articular cartilage abnormalities in dysplastic hips without joint space narrowing. AB - Three-dimensional magnetic resonance imaging in the coronal and sagittal planes was performed in 25 normal hips of 16 volunteers and 70 dysplastic hips of 50 patients with clinical symptoms but without radiologic joint space narrowing. A high prevalence of cartilage abnormalities was detected, mostly located at the anterosuperior area in the hip: 31 hips (44%) in the acetabular cartilage and five hips (7%) in the femoral cartilage showed a mild to moderate defect of cartilage thickness. The presence of cartilage abnormalities had a statistically significant correlation with age of the patients and severity of hip pain. Of 31 hips with cartilage abnormalities, sagittal magnetic resonance images showed abnormalities in 30 (97%), whereas coronal magnetic resonance images revealed abnormalities only in 11 (35%). A high incidence of cartilage abnormalities in the preradiologic stage suggests the need for more sensitive modalities for early diagnosis. Magnetic resonance imaging in the sagittal plane allows detailed assessment of early cartilage abnormalities. PMID- 11210953 TI - Atraumatic osteonecrosis of the patella. AB - Atraumatic secondary osteonecrosis of the patella is a rare entity and has been reported in only several case reports. The purpose of this study was to define the clinical and radiographic characteristics and outcome of this disease. Osteonecrosis of the patella was found in 25 knees in 19 patients. The mean age was 42 years (range, 21-63 years). Eighteen (95%) patients had greater than 2 g of lifetime corticosteroid exposure, and six (32%) patients had systemic lupus erythematosus. Osteonecrosis was found in the superior pole of the patella in all 23 knees (17 patients) that had magnetic resonance imaging. Osteonecrosis was apparent on plain radiographs in five knees (20%) in four patients, and only one knee (4%) in one patient had collapse of the posterior articulating surface of the patella. One (4%) patient presented with anterior knee pain localized to the patella. At a mean followup of 4 years (range, 2-18 years), none of the patients had an intervention that focused on treating the patellar lesion. Patellar osteonecrosis is characterized by patients with coincident lesions of the distal femur and the proximal tibia and lesions localized to the superior pole of the patella. It is a nonprogressive disease that does not warrant surgical exploration. PMID- 11210954 TI - Graduated compression stockings: knee length or thigh length. AB - The mechanisms by which graduated compression stockings prevent deep venous thrombosis are not completely understood. In the current study the physiologic effect of low-pressure graduated compression stockings on the venous blood flow in the lower limb and the practical aspects of their use were assessed. Patients having elective orthopaedic surgery at a university orthopaedic department were randomized into five groups to wear two different types of graduated compression stockings in thigh and knee lengths. Patients in the fifth control group did not wear graduated compression stockings. Venous occlusion strain gauge plethysmography was used to measure venous flow. After 20-minutes bed rest there was a highly significant increase in venous capacitance and venous outflow in patients in all of the four groups wearing stockings. There was no difference in the mean of the percentage change of venous capacitance in patients in the four groups wearing stockings. The knee length Brevet stockings were less efficient in increasing the venous outflow. There was no significant change in the venous capacitance and venous outflow in patients in the control group. Visual assessment of the fit and use of stockings was done, and patients' subjective opinion of comfort was sought. The knee length graduated compression stockings wrinkled significantly less, and significantly fewer patients reported discomfort with them. All stockings were reported to be difficult to use. Thigh and knee length stockings have a significant effect on decreasing venous stasis of the lower limb. Knee length graduated compression stockings are similarly efficient in decreasing venous stasis, but they are more comfortable to wear, and they wrinkle less. PMID- 11210955 TI - Health related quality of life in patients with dysvascular transtibial amputation. AB - Sixty adults with transtibial amputations completed a validated outcomes instrument assessing their prosthesis related quality of life. All had their amputations because of peripheral vascular disease or nonsalvageable diabetic foot infection. Of the patients, 46 were male and 14 were female. Forty-four had diabetes. All of the subjects used a prosthesis for a minimum of 6 months. The Prosthetic Evaluation Questionnaire measured prosthesis function (usefulness, residual limb health, and appearance), mobility (ambulation and transfers), psychosocial response (perceived responses, frustration, and social burden), well being, and satisfaction. Scoring was accomplished using a linear analog scale, with poor responses rated as 0 and excellent responses rated as 100. Mobility scores were the lowest (ambulation, 55.3; transfer, 64.6). Functional scores were slightly better (usefulness, 65.7; residual limb health, 79.7; and appearance, 73.3). Psychosocial response scored best (perceived responses, 86.6; frustration, 69.1; and social burden, 66.4). The overall well-being scale graded at 67.0, and overall satisfaction scored at 65.2. Although experts in rehabilitation would expect function and mobility scores to be highest and psychosocial scores to be lowest, this population actually perceived the reverse to be true. These data provide realistic expectations for patients faced with transtibial amputation and a benchmark to measure newer treatment modalities or technical innovations. PMID- 11210956 TI - A method for evaluating the results of tendon transfers for foot drop. AB - A system for assessing the results of tibialis posterior tendon transfers in the treatment of foot drop secondary to nerve palsy is proposed. There are seven sections to this scoring system: pain, need for orthosis, ability to wear normal shoes, activity level, muscle power of ankle dorsiflexion, degree of active ankle dorsiflexion, and foot posture. The total score is 100. The results are classified as excellent for scores between 85 and 100, good between 70 and 84, fair between 55 and 69, and poor for scores below 55. The results of 18 patients (mean followup, 64.6 months) who had a tibialis posterior tendon transfer were assessed using this method. Four patients (22.2%) had an excellent result, seven (38.8%) had a good result, two (11.1%) had a fair result, and five (27.7%) had a poor result. The average score was 67.2, suggesting an overall fair result for this operation. In nine patients, there was correlation between the outcome when assessed with this method and with patient rating. In two patients, the outcomes were better when assessed with this method than with patient rating, whereas the reverse was true in seven other patients. Thus, this system may provide a more objective and critical evaluation of tibialis posterior transfers for foot drop. PMID- 11210957 TI - Variations in the skeletal morphologic features of the wrist. AB - Increased attention to and interest in the wrist and the field of hand surgery has brought about the discovery, rediscovery, and better description of variations in the skeletal morphologic features of the hand and wrist. In the second through fifth carpometacarpal joints, the fourth carpometacarpal articulation is the area of greatest variability. In the midcarpal joint, the scaphotrapeziotrapezoid and the capitolunate (hamate) articulations are areas of considerable variability in their skeletal morphologic features. New knowledge and awareness of variations in skeletal morphologic features in the carpus offer a better understanding and the opportunity to revisit various injury patterns and/or orthopaedic problems, and normal kinetics and kinematics to assess the effect and any differences that may be related to these different skeletal morphologic features. PMID- 11210958 TI - Tibial turn-up for long distal femoral bone loss. AB - Since 1990, seven patients have been treated by the authors with the tibial turn up procedure. They have ranged in age from 8 to 37 years; four were skeletally mature adults and three were children. All seven patients were faced with a clinical situation that required surgical removal of a long portion of their affected distal femur. Three of the adult patients initially were treated for osteosarcoma with long distal femoral resections and allograft arthrodesis of the knee. The allografts ultimately failed, two because of aseptic failure and one because of infection. One patient required distal femoral removal for chronic osteomyelitis and pathologic fracture. Of the three children who were treated, two had turn-ups after long resection of the distal femur for bone malignancy, and one had a secondary turn-up after failure of a long distal femoral endoprosthesis. The technique uses the normal ipsilateral tibia as a vascularized pedicle graft to restore femoral length. The ultimate result, even after very high above knee resection, is a long above knee amputation stump. The followup of the patients in the current study ranged from 2 to 8 years. All patients achieved healing and were able to wear above knee prostheses. The tibial turn-up is an effective procedure that results in a long functional above knee amputation stump even after very high above knee resections. PMID- 11210959 TI - Treatment of giant cell tumor of the distal radius. AB - The results of surgical treatment of giant cell tumors of the distal radius were reviewed in 12 patients between 1982 and 1995. All 12 patients had Grade III lesions. Six of the 12 patients were treated using intralesional curettage with local excision, and the other six patients underwent en bloc resection with total condyle (four of the six by osteoarticular allograft, and the other two by fibular autograft) reconstruction with the aim of preserving the functional joint. There were no early or late complications such as infection, graft fracture, implant failure, or nonunion. No local tumor recurrence was seen in either group during the average followup of 6 years (range, 3-16 years). The best functional result was seen in the patients treated with intralesional curettage. The functional result of the resection group was good, achieving an average of 69% (range, 56%-83%) of their range of motion and 70% (range, 63%-77%) of their grip strength on the contralateral side. Intralesional excision should not be excluded as a possible treatment of Grade III lesions, although en bloc resection was used more commonly for these lesions because of tumor surgery reasons. Grade III lesions were treated with curettage when the tumor did not invade the wrist, destroy more than 50% of the cortex, or break through the cortex with an extraosseous mass in more than one plane. Reconstruction with osteoarticular allograft after en bloc resection is recommended in this non-weightbearing joint when there is contraindication for curettage of the lesion. PMID- 11210960 TI - Displaced femoral neck fractures in the elderly: outcomes and cost effectiveness. AB - The optimal treatment for displaced femoral neck fractures in elderly patients is a matter of controversy. Four surgical options are well supported in the orthopaedic literature: reduction with internal fixation, unipolar hemiarthroplasty, bipolar hemiarthroplasty, and total hip arthroplasty. Based on a review of the outcomes literature regarding treatment of femoral neck fractures and a cost-effectiveness analysis, an algorithm for surgical treatment of displaced femoral neck fractures in elderly patients is presented. Cost effectiveness analysis of these four surgical treatment options shows that arthroplasty is the most cost-effective treatment when complication rate, mortality, reoperation rate, and function are evaluated during a 2-year postoperative period. These data were strongly supported by a two-way sensitivity analysis that varied the effectiveness of the interventions and the costs. Literature derived outcome studies show that elderly patients with displaced femoral neck fractures achieve the best functional results with a well healed femoral neck without osteonecrosis after reduction and internal fixation. Achieving this result may be difficult, and it is not as cost effective as arthroplasty. PMID- 11210961 TI - Arthroscopic reduction and internal fixation of tibial plateau fractures in skiing. AB - Arthroscopic reduction and internal fixation of tibial plateau fractures can facilitate restoration of articular congruity while permitting rigid fracture stabilization. Twenty-five patients who underwent arthroscpoic reduction and internal fixation of a tibial plateau fracture were reviewed. The average age of the patients was 45. At a mean followup of 24 months, 76% of patients rated their result as excellent and 16% as good. Eighty-four percent returned to full sporting activity. There were no episodes of nonunion, failure of fixation, wound infection, deep venous thrombosis, compartment syndrome, or arthrofibrosis. Preoperative fracture depression averaged 7.7 mm (range, 1-18 mm). Fracture depression at final followup averaged 0.8 mm (range, 0-5 mm). Sixty-four percent of patients had associated intraarticular injury diagnosed and treated at the time of arthroscopy. Arthroscopic reduction and internal fixation provides an accurate assessment of, and allows definitive treatment for, intraarticular injuries associated with tibial plateau fractures. The technique allows less soft tissue stripping than with traditional arthrotomy, better visualization of the articular surface, early return to physical activities, and obviates the need for meniscal detachment and repair. PMID- 11210962 TI - Neutralization of fibroblast growth factor-2 reduces intraarticular adhesions. AB - Adhesion is a serious complication after trauma or surgery. Because adhesion formation is essentially a fibrogenetic process, a series of growth factors are assumed to be involved in its development. If this is true, it may be possible that inhibition of the growth factor activity suppresses adhesion formation. The current study was conducted to verify this hypothesis on fibroblast growth factor 2 using an intraarticular adhesion model in the rabbit knee. Forty Japanese White rabbits were used. They were divided randomly into five groups of eight animals, and in three of them, activity of endogenous fibroblast growth factor-2 was suppressed locally by a neutralizing antibody. The remaining two groups served as controls, and formation of adhesions was evaluated 4 weeks after surgery. The results showed that the administration of the antibody reduced the extent of adhesions macroscopically, whereas histologic observation and collagen content measurement suggested the adhesion tissue was not affected significantly. Corresponding to the macroscopic findings, contraction of the knee was improved in the antibody groups. The findings showed that suppression of fibroblast growth factor-2 activity reduces adhesions. It is expected that control of the cytokine activity may become a novel method for reducing adhesions. PMID- 11210963 TI - Selective drug resistant human osteosarcoma cell lines. AB - Chemotherapy in combination with surgery has been shown to be effective for the control of osteosarcoma. Development of resistance to chemotherapeutic agents is a recurring clinical problem. To investigate this phenomena, human osteosarcoma cells, TE-85, were exposed to increasing doses of Taxol or Taxotere during a 9 month period. Highly resistant subclones (TE-85TXL; TE-85TXR, respectively) were developed. Chemosensitivities are presented for TE-85 cell line and these new lines to Taxol, Taxotere, doxorubicin, cisplatin, and topotecan. Drug concentrations that inhibited cell growth by 50% compared with untreated cells were determined. The TE-85TXL cells showed resistance greater than 1,000-fold to Taxol and Taxotere and 60-fold to doxorubicin. The TE-85TXR cells showed resistance greater than 1,000-fold to Taxol, 800-fold to Taxotere, and 90-fold to doxorubicin. There was little cross resistance to topotecan and enhanced sensitivity to cisplatin. The role of P-170 glycoprotein in Taxol and Taxotere resistance was explored. Coincubation with verapamil, to block the actions of P 170 glycoprotein, partly reversed resistance to Taxol, Taxotere, and doxorubicin in both cell lines. Anti-P-170 glycoprotein antibodies revealed positive staining in TE-85TXL and TE-85TXR cell lines. Flow cytometry revealed reduced accumulation of doxorubicin in resistant cells. These data indicate that a human osteosarcoma cell line will develop resistance to Taxol and Taxotere, which is mediated in part by the P-170 glycoprotein. PMID- 11210964 TI - Combined effects of estrogen and progesterone on the anterior cruciate ligament. AB - Previous studies from the authors' laboratory have established the presence of estrogen and progesterone receptors in the human anterior cruciate ligament. The purpose of the current study was to investigate the combined effects of 1beta estradiol and progesterone on cell proliferation and procollagen synthesis of the human anterior cruciate ligament fibroblasts. Fibroblast proliferation and procollagen synthesis in response to logarithmic concentrations of 17beta estradiol (0.0025 ng/mL, 0.025 ng/mL, 0.25 ng/mL) and progesterone (1 ng/mL, 10 ng/mL, 100 ng/mL) were assessed with the measurement of 3H-thymidine incorporation and Types I and III procollagen specific equilibrium radioimmunoassays. On Days 1, 3, and 5 there was a dose dependent decrease in the fibroblast proliferation and procollagen Type I synthesis with increasing estradiol concentrations. The effect was attenuated with increasing progesterone concentrations. Controlling for estrogen levels, a dose dependent increase in fibroblast proliferation and procollagen Type I synthesis was observed with increasing progesterone concentrations. The effect was more pronounced at lower concentrations of estrogen, suggesting estrogen levels were the dominant factor. The effects of estrogen and progesterone became less apparent by Day 7. No significant differences in Type III procollagen synthesis were seen with varying estradiol concentrations at any of the designated times. These early physiologic changes in fibroblast proliferation and Type I procollagen synthesis may provide a biologic explanation for the increased anterior cruciate ligament injury rate observed in female athletes, suggesting the acute cyclical hormonal variations in the female athlete during menstruation predispose her to ligamentous injury. PMID- 11210965 TI - Cleidocranial dysostosis and the unity of the Homeric epics: an essay. AB - Numerous years ago, in this journal, Beasley diagnosed the character Thersites from Homer's Iliad with cleidocranial dysostosis. Additional evidence from the text is presented to support a diagnosis of cleidocranial dysostosis, and it is pointed out that this diagnosis may have implications in studying the question whether the two Homeric epics (the Iliad and the Odyssey) were composed by the same author. PMID- 11210966 TI - The anatomy of the ligaments of the wrist and distal radioulnar joints. AB - The ligaments of the wrist are responsible for guiding and constraining the complex motion of the carpal bones relative to the forearm bones, the metacarpals, and contiguous carpal bones. The majority of wrist ligaments are found within the joint capsule as organized thickenings composed of parallel collagen fascicles, small caliber nerves and blood vessels, and lined on their deep surfaces by synoviocytes. The palmar radiocarpal ligament complex is composed of the radioscaphocapitate, long radiolunate, radioscapholunate and short radiolunate ligaments. The ulnocarpal ligaments include the ulnolunate, ulnotriquetral and ulnocapitate ligaments. Dorsally, the radiocarpal joint is spanned by the dorsal radiocarpal ligament. Palmar ligaments connecting the proximal and distal carpal rows include the scaphotrapeziotrapezoid, scaphocapitate, triquetrocapitate and triquetrohamate ligaments. Within each row are interosseous ligaments connecting adjacent carpal bones, each divisible into dorsal and palmar components. There are unique regions within some of the ligaments, such as a zone of fibrocartilage in the proximal regions of the scapholunate and lunotriquetral interosseous ligaments, and strong deep regions connecting the trapezoid, capitate, and hamate. The distal radioulnar joint is connected by the triangular fibrocartilage complex, composed of a fibrocartilaginous disc and the palmar and dorsal radioulnar ligaments. The ulnocarpal ligaments attach to the palmar radioulnar ligament rather than directly to the ulna, allowing increased independence between wrist and forearm motion. PMID- 11210967 TI - Comparative mobility of muscles as a guide in surgical exposures. 1940. PMID- 11210968 TI - Arterial patterns of the deep and superficial palmar arches. AB - The vascular patterns of the palmar arches and their interconnecting branches present a complex and challenging area of study. Improvements in microsurgical techniques have made a better understanding of vascular patterns and vessel diameters more important. Forty-five fresh limbs from cadavers were amputated at the level of the midhumerus. Ward's red latex or Batson's compound was injected under pressure to visualize the arterial system in the hand. After hardening of the injected material, the skin, subcutaneous tissues, and tendons were removed. The specimens were digested in concentrated potassium or sodium hydroxide leaving the bony elements and a cast of the arterial system. The superficial palmar arch is most easily classified into two categories: complete or incomplete. An arch is considered to be complete if an anastomosis is found between the vessels constituting it. An incomplete arch has an absence of a communication or anastomosis between the vessels constituting the arch. Complete superficial palmar arches were seen in 84.4% of specimens. In the most common type, the superficial arch was formed by anastomosis between the superficial volar branch of the radial artery and the ulnar artery. This was seen in 35.5% of specimens. In 31.1%, the arch was formed entirely of the ulnar artery. Incomplete superficial arches were seen in 15.5% of specimens. In 11.1%, the ulnar artery forms the superficial arch but does not contribute to the blood supply to the thumb and index finger. The deep palmar arch was found to be less variable with 44.4% formed by an anastomosis between the deep volar branch of the radial artery and the inferior deep branch of the ulnar artery. Injection followed by chemical debridement allows direct visualization and measurement of the arches and the smaller arterial branches that are visualized poorly with other techniques. Based on the vessel measured, vessels of the superficial and deep arches are of sufficient size to allow microvascular repair, although repair of the communicating branches, the dorsal carpal rete, and its branches, probably is not feasible because of their small size. PMID- 11210969 TI - Vascularity of the carpus. AB - Relatively few studies investigating the vascular patterns of the carpus have been performed. Technical difficulties in identifying small vessels in three dimensions and in determining their location within the thick ligaments about the wrist have led to conflicting anatomic reports. Studies on cadavers in which improved techniques with arterial injection, chemical debridement, and decalcification were used allowed the arterial anatomy of the carpus to be delineated more accurately. The current authors review these arterial patterns, with attention given to the extraosseous and intraosseous vascularities. PMID- 11210970 TI - Vascular anatomy of the distal radius: implications for vascularized bone grafts. AB - The vascular anatomy of the distal radius and ulna is complex with a series of longitudinal vessels anastomosing with a series of arches. This complex anastomotic network of vessels has a consistent spatial relationship to surrounding anatomic structures and is constant in nature. Knowledge of the vascular anatomy of the distal radius and ulna has allowed the creation of numerous reverse flow pedicled vascularized bone grafts, which can be applied to carpal pathologic features to assist in the healing of difficult fractures or avascular necrosis. The anatomy and terminology of the vascular network and the implications, indications, and applications of this anatomy to carpal pathologic features is reviewed. PMID- 11210971 TI - Upper extremity peripheral nerve anatomy: current concepts and applications. AB - The nerve anatomy of the upper extremity is studied constantly through surgical findings, electrodiagnostic studies, and cadaveric dissections. Although it is recognized that the anatomy is not changing rapidly, knowledge of the anatomic relationships and their significance is increasing. The purpose of the current study is to provide a comprehensive analysis of the nerve anatomy of the upper extremity to include innervation patterns, critical landmarks, and clinical applications, with particular focus on recent contributions in the literature. PMID- 11210972 TI - Anatomy and functional significance of the long extensors to the fingers and thumb. AB - Intrinsic and extrinsic hand muscles power finger extension. These two muscle groups have different anatomy that allows complimentary function at the interphalangeal joints and opposing function at the metacarpophalangeal joints. Independent extension of each finger is not possible because of anatomic constraints including the juncturae tendinum and intertendinous fascia between the extrinsic extensor tendons on the dorsum of the hand. Anatomic variations of the extrinsic extensor tendons are frequent and knowledge is important when assessing the traumatized or diseased hand. PMID- 11210973 TI - Palmar and digital flexor tendon pulleys. AB - Retinacular structures, called pulleys, maintain the flexor tendons of the hand in constant relationship to the joint axes and promote economy and efficiency in finger flexion. This system is composed of the transverse carpal ligament, the palmar aponeurosis pulley, and the digital flexor pulley system. Of these three components, the digital pulleys are the most critical to finger flexion. In their normal state, these pulley components are ideal in all aspects including configuration and location, which accomodates a 260 degrees arc of motion without impingement and with minimum friction while at the same time using muscle tendon excursion that is well within the natural range of the muscle. An absent pulley results in an increased moment arm and requires increased tendon excursion to produce the same arc of motion. Because muscle excursion is not a limitless factor and is directly proportional to muscle fiber length, the effectiveness of tendon excursion is dependent on maintenance of the critical relationship between pulleys and the adjacent joints. Preservation and reconstruction of this system is based on knowledge of the anatomy and an understanding of the relative functional significance of each component of the system. PMID- 11210974 TI - The dorsal aponeurosis, intrinsic, hypothenar, and thenar musculature of the hand. AB - The intrinsic muscles of the hand consist of seven interossei and four lumbrical muscles. With the extrinsic long extensors, the intrinsic muscles act via the dorsal aponeurosis to control finger motion. The interossei also control finger abduction and adduction, and flexion of the metacarpophalangeal joints. The lumbricals are the main extensors of the interphalangeal joints. The complex structure of the dorsal aponeurosis allows coordination and individual joint motion. The muscles of the hypothenar and thenar eminences also insert into the dorsal aponeurosis and the skeleton of the small finger and thumb, respectively, and are responsible for the specialized motion. Knowledge of the anatomy is necessary for understanding the function in treating abnormalities and trauma to the intricate structures of the hand. PMID- 11210985 TI - Nurse telephone-triage. PMID- 11210986 TI - Two cheers for inhaled insulin. PMID- 11210987 TI - Osteoporosis in patients with organ transplants: a neglected problem. PMID- 11210988 TI - Can survival be prolonged for patients with hormone-resistant prostate cancer? PMID- 11210989 TI - Helicobacter pylori and sudden-infant-death syndrome. PMID- 11210990 TI - Retaining trust. PMID- 11210991 TI - Habituation technique in study of development of fetal behaviour. PMID- 11210992 TI - New cells from old. PMID- 11210993 TI - Efficacy of inhaled human insulin in type 1 diabetes mellitus: a randomised proof of-concept study. AB - BACKGROUND: Effective glycaemic control in type 1 diabetes mellitus usually requires two or more insulin injections daily. Inhaled intrapulmonary delivery of insulin offers a potential new way to deliver meal-related insulin, eliminating the need for preprandial injections. METHODS: 73 patients with type 1 diabetes mellitus were studied in an open-label, proof-of-concept, parallel-group randomised trial. Patients in the experimental group received preprandial inhaled insulin plus a bedtime subcutaneous ultralente insulin injection. Patients in the control group received their usual insulin regimen of two to three injections per day. Participants monitored their blood glucose four times daily, and adjusted insulin doses weekly to achieve preprandial glucose targets of 5.6-8.9 mmol/L. The primary outcome measure was change in glycosylated haemoglobin (HbA1c) after 12 weeks. Secondary outcomes were fasting and postprandial glucose response to a mixed meal; hypoglycaemia frequency and severity; pulmonary function; and patients' satisfaction. FINDINGS: Changes in HbA1c were indistinguishable between groups (difference 0.2% [95% CI -0.2 to 0.5]). Changes in fasting and postprandial glucose concentrations, and occurrence and severity of hypoglycaemia were also similar between groups. Inhaled insulin was well tolerated and had no effect on pulmonary function (ie, spirometry, lung volumes, diffusion capacity, and oxygen saturation). INTERPRETATION: This proof-of-concept study shows that preprandial insulin can be given by inhalation in individuals with insulin deficient type 1 diabetes as a less invasive alternative to conventional preprandial insulin injections. PMID- 11210995 TI - Clinical picture: human babesiosis. PMID- 11210994 TI - Bone-targeted therapy for advanced androgen-independent carcinoma of the prostate: a randomised phase II trial. AB - BACKGROUND: Prostate carcinoma is linked to osteoblastic metastasis. We therefore investigated the value of bone-targeted consolidation therapy in selected patients with advanced androgen-independent carcinoma of the prostate. METHODS: 103 patients received induction chemotherapy, consisting of ketoconazole and doxorubicin alternating with estramustine and vinblastine. After two or three cycles of induction chemotherapy, we randomly assigned 72 patients who were clinically stable or responders to receive doxorubicin with or without strontium 89 (Sr-89) every week for 6 weeks. FINDINGS: Overall 62 of the 103 (60%, 95% CI 50-70) patients had a 50% or greater reduction in serum prostate-specific antigen concentration that was maintained for at least 8 weeks, and 43 (42%, 32-52) had an 80% or greater reduction. 49 (52%) patients with bone pain at registration had complete resolution of pain. After follow-up of 67 patients until death, the estimated median survival for all 103 patients was 17.5 months (range 0.5-37.7). For the 36 patients randomly assigned to receive Sr-89 and doxorubicin, the median survival time was 27.7 months (4.9-37.7), and for the 36 who received doxorubicin alone it was 16.8 months (4.4-34.2) (p=0.0014). The hazard ratio was 2.76 (95% CI 1.44-5.29). INTERPRETATION: Bone-targeted consolidation therapy consisting of one dose of Sr-89 plus doxorubicin once a week for 6 weeks, when given to patients with stable or responding advanced androgen-independent carcinoma of the prostate after induction chemotherapy, improved overall survival. PMID- 11210996 TI - Frequency and predictors of osteoporotic fractures after cardiac or liver transplantation: a follow-up study. AB - BACKGROUND: Osteoporosis and related fractures are a major complication after organ transplantation. The aim of this study was to find out the frequency and predictors of osteoporotic fractures after cardiac or liver transplantation. METHODS: 235 consecutive patients who had a cardiac transplant (n=105; 88 men, 17 women) or a liver transplant (130; 75 men, 55 women) were followed. Vertebral fractures were assessed by a standardised analysis of spinal radiographs before and annually after transplantation. Clinical and non-vertebral fracture data were noted from hospital records. FINDINGS: In the first and second years after transplantation, the proportion of patients (Kaplan-Meier estimates) who had at least one vertebral fracture was slightly higher in the cardiac group (first year 21%, second year 27%) than in the liver group (first year 14%, second year 21%). In the third and fourth years, one third of patients from both groups had had one or more vertebral fractures. Non-vertebral fractures occurred in nine patients (7%) after liver transplantation and avascular necrosis of the hip head in three patients (3%) after cardiac transplantation. In both groups, no dose-dependent effect of immunosuppressive therapy on fracture development could be identified. Independent predictors assessed by multivariate analysis were age (hazard ratio [95% CI] increase of 5 years, 1.71 [1.1-2.7]) and lumbar bone-mineral density (decrease of 1 SD t score, 1.97 [1.2-3.2]) in cardiac transplantation patients, and vertebral fractures before transplantation (6.07 [1.7-21.7]) in the liver group. INTERPRETATION: The high frequency of osteoporotic fractures in the 2 years after transplantation and the limitations of reliable fracture-risk predictions, show the need to investigate preventive therapies. PMID- 11210997 TI - Observations on recurrent syncope and presyncope in 641 patients. AB - BACKGROUND: Syncope is a common disorder that is potentially disabling and affects both young and old. Once neurological, cardiological, and metabolic causes have been excluded, there remains a group in which diagnosis is unclear; some may have an autonomic basis. We therefore did a retrospective study on consecutive patients referred to our tertiary referral autonomic centres between 1992 and 1998 with recurrent syncope and presyncope, in whom non-autonomic causes, before referral, had been sought and excluded. The object was to find out whether autonomic investigation helped diagnosis. METHODS: Data from case notes and from the autonomic database on 641 patients were analysed. Syncopal patients with a known or provisional diagnosis of autonomic failure were excluded from analysis. The role of screening tests in establishing or excluding an autonomic cause was assessed. Response to additional autonomic tests (such as head-up tilt with or without venepuncture, and food challenge and exercise) was documented. Some patients underwent further testing if non-autonomic neurological, psychiatric, and other disorders were considered. FINDINGS: Screening autonomic function tests indicated orthostatic hypotension and confirmed chronic autonomic failure in 31 (4.8%) patients. Neurally mediated syncope was diagnosed in 279 (43.5%) on the basis of clinical features and autonomic testing. Most had vasovagal syncope (227 [35%]); other causes included carotid sinus hypersensitivity (37 [5.8%]), and a group of 15 (2.3%) were associated with rarer causes such as micturition and swallowing. Miscellaneous cardiovascular causes (systemic hypotension, arrhythmias), or drugs, contributed to syncope in 53 (8.3%). Non-autonomic neurological causes included vestibular dysfunction (32 [5%]) and epilepsy (11 [1.7%]). In 56 (8.7%) a psychiatric cause was thought to be contributory. In 179 (27.9%), syncope was of unknown cause. INTERPRETATION: In recurrent syncope and presyncope, when cardiac, neurological, and metabolic causes have been excluded, autonomic investigation can aid management by making, confirming, or excluding various factors or diagnoses. PMID- 11210998 TI - Brain dopamine and obesity. AB - BACKGROUND: The cerebral mechanisms underlying the behaviours that lead to pathological overeating and obesity are poorly understood. Dopamine, a neurotransmitter that modulates rewarding properties of food, is likely to be involved. To test the hypothesis that obese individuals have abnormalities in brain dopamine activity we measured the availability of dopamine D2 receptors in brain. METHODS: Brain dopamine D2 receptor availability was measured with positron emission tomography (PET) and [C-11]raclopride (a radioligand for the dopamine D2 receptor). Bmax/Kd (ratio of the distribution volumes in striatum to that in cerebellum minus 1) was used as a measure of dopamine D2 receptor availability. Brain glucose metabolism was also assessed with 2-deoxy 2[18F]fluoro-D-glucose (FDG). FINDINGS: Striatal dopamine D2 receptor availability was significantly lower in the ten obese individuals (2.47 [SD 0.36]) than in controls (2.99 [0.41]; p < or = 0.0075). In the obese individuals body mass index (BMI) correlated negatively with the measures of D2 receptors (r=0.84; p < or = 0.002); the individuals with the lowest D2 values had the largest BMI. By contrast, neither whole brain nor striatal metabolism differed between obese individuals and controls, indicating that striatal reductions in D2 receptors were not due to a systematic reduction in radiotracer delivery. INTERPRETATION: The availability of dopamine D2 receptor was decreased in obese individuals in proportion to their BMI. Dopamine modulates motivation and reward circuits and hence dopamine deficiency in obese individuals may perpetuate pathological eating as a means to compensate for decreased activation of these circuits. Strategies aimed at improving dopamine function may be beneficial in the treatment of obese individuals. PMID- 11210999 TI - Congestive heart failure in a hypertensive patient (don't forget the stethoscope). PMID- 11211000 TI - Pseudoexfoliation syndrome and aneurysms of the abdominal aorta. AB - We assessed the association between pseudoexfoliation syndrome, a common age related fibrillopathy of unknown cause, and vascular diseases, especially aneurysms of the abdominal aorta. In a prospective single-blind study we ophthalmoscopically examined 55 patients with aneurysms of the abdominal aorta and 41 controls with carotic-artery occlusion. 24 of 55 patients with aortic aneurysm showed signs of manifest (17 of 55 patients) or early-stage (seven of 55) pseudoexfoliation syndrome. Eight of 41 control patients showed manifest (seven of 41 patients) and early (one of 41) ocular pseudoexfoliation (p=0.016). These findings, including histopathological examinations, suggest an association between aneurysms of the abdominal aorta and pseudoexfoliation syndrome. PMID- 11211001 TI - Genetic resistance factor for HIV-1 and immune response to varicella zoster virus. AB - A 32 bp deletion in the chemokine receptor CCR5 gene modulates HIV-1 infection. However, whether this CCR5 gene variation modifies immunity to common herpesvirus infections is unknown. We investigated whole blood IgG concentrations of 157 normal adult blood donors. Also we assessed whether the 32 bp deletion of CCR5 (delta32CCR5) was associated with circulating IgG to four herpesviruses: varicella zoster virus, Epstein-Barr virus, cytomegalovirus, and herpes simplex virus type 1 and type 2. Individuals who carried delta32CCR5 were 9.2 times more likely to be seronegative for varicella zoster virus than non-carriers (95% CI 2.9-29.1), but no differences were seen for the other herpesviruses studied. Variation in CCR5 may modulate humoral immunity to varicella zoster virus. PMID- 11211002 TI - Constitutively raised serum concentrations of mast-cell tryptase and severe anaphylactic reactions to Hymenoptera stings. AB - Anaphylactic IgE-mediated reactions to Hymenoptera stings vary in their severity for reasons that are not clear. We investigated patients with a history of systemic anaphylatic reactions to honeybee or wasp stings. Nine (75%) of 12 patients with raised tryptase concentrations but only 28 (28%) of 102 patients with lower tryptase concentrations, had a history of severe sting reactions (p=0.004). Raised baseline serum concentrations of mast-cell tryptase and mastocytosis are potential risk factors for severe allergic reactions to Hymenoptera venom. PMID- 11211003 TI - Losartan and fetal toxic effects. AB - We report a case of maternal exposure to the antihypertensive drug losartan during weeks 20-31 of pregnancy. We saw the fetal toxic effects of oligohydramnios (decreased amniotic fluid), fetal pulmonary hypoplasia, fetal hypoplastic skull bones, and subsequent fetal death. This pattern of abnormalities is similar to those seen in exposure to angiotensin-converting enzyme (ACE) inhibitors during pregnancy, and were probably caused by losartan. PMID- 11211004 TI - How medical students learn spatial anatomy. AB - Despite its importance in clinical tasks, spatial learning is poorly understood. We did a randomised, single-blind study on 146 medical students to assess the effectiveness of student-controlled multiple views on the spatial learning process. High spatial ability of the student, and self-directed examination of an object from multiple different perspectives improves spatial learning. PMID- 11211005 TI - 105,000 body parts retained in the UK, census says. PMID- 11211006 TI - Memory gain means more pain for transgenic mice. PMID- 11211007 TI - A genetic explanation for premature ovarian failure? PMID- 11211008 TI - Are health internet companies heading for extinction? PMID- 11211009 TI - Authorities overstretched as earthquake death toll increases. PMID- 11211010 TI - Brazil's government to redress health-care inequalities. PMID- 11211011 TI - Namibian government to prosecute healers. PMID- 11211012 TI - Slow start to South Africa's antenatal HIV programme. PMID- 11211013 TI - Reliable assessment of the effects of treatment on mortality and major morbidity, I: clinical trials. AB - This two-part review is intended principally for practising clinicians who want to know why some types of evidence about the effects of treatment on survival, and on other major aspects of chronic disease outcome, are much more reliable than others. Although there are a few striking examples of treatments for serious disease which really do work extremely well, most claims for big improvements turn out to be evanescent. Unrealistic expectations about the chances of discovering large treatment effects could misleadingly suggest that evidence from small randomised trials or from non-randomised studies will suffice. By contrast, the reliable assessment of any more moderate effects of treatment on major outcomes--which are usually all that can realistically be expected from most treatments for most common serious conditions--requires studies that guarantee both strict control of bias (which, in general, requires proper randomisation and appropriate analysis, with no unduly data-dependent emphasis on specific parts of the overall evidence) and strict control of random error (which, in general, requires large numbers of deaths or of some other relevant outcome). Past failures to produce such evidence, and to interpret it appropriately, have already led to many premature deaths and much unnecessary suffering. PMID- 11211014 TI - Proliferation-inducing viruses in non-permissive systems as possible causes of human cancers. AB - Animal viruses, some of which are probably unable to replicate in human cells, could be transmitted to people where they may be linked to tumours currently not attributed to viruses. Several human virus types have oncogenic potential in animals. A potential risk for acquiring such infections by handling and preparation of animal products was analysed against the background of available epidemiological reports. Human tumours should be systematically assessed for proliferation-inducing viruses in non-permissive systems. PMID- 11211015 TI - Is the normalisation of blood pressure in bleeding trauma patients harmful? PMID- 11211016 TI - Basiliximab in paediatric liver-transplant recipients. PMID- 11211017 TI - Basiliximab in paediatric liver-transplant recipients. PMID- 11211018 TI - Effect of pregnancy on chronic hepatitis C. PMID- 11211019 TI - Violence in the USA. PMID- 11211020 TI - Nearwork and myopia in young children. PMID- 11211021 TI - Antipsychotic drugs and venous thromboembolism. PMID- 11211022 TI - Antipsychotic drugs and venous thromboembolism. PMID- 11211023 TI - Prevention of nevirapine-associated rash. PMID- 11211024 TI - Prevention of nevirapine-associated rash. PMID- 11211025 TI - Fibre supplementation. PMID- 11211026 TI - IVF for unmarried women. PMID- 11211027 TI - Group B streptococci for neonatal disease. PMID- 11211028 TI - Group B streptococci for neonatal disease. PMID- 11211029 TI - Bilateral testicular tumour in neurofibromatosis type 1. PMID- 11211030 TI - Antibiotic therapy and peritonitis. PMID- 11211031 TI - Academic harassment. PMID- 11211032 TI - Presentation of in-vitro fertilisation results. PMID- 11211033 TI - BSE report. PMID- 11211034 TI - A challenge for reform in South Korea. PMID- 11211035 TI - FDAMA's written request list: medicines for children. PMID- 11211036 TI - Lovesickness. PMID- 11211037 TI - Dynamic strength capabilities of small-stature females to eject and support added head weight. AB - BACKGROUND: Naval Air Warfare Center Aircraft Division investigated the abilities of small-stature females (< or = 120 lb) to fly under G-stress using the Dynamic Flight Simulator (DFS) and its tactical fight/attack cockpit, displays and controls. OBJECTIVES: Determine ability to exert NACES ejection seat actuation pull force under static, acceleration and simulated flight conditions; support up to 5 lb of added head weight (AHW) under catapult, arrestment, and aerial combat maneuver G-loads; and reach all controls. METHODS: Seven female subjects (six small and one medium stature) participated. The AHW task included three helmet weights, 3.5 lb (standard configuration), 4.25 lb and 5 lb and subjects were tasked to accurately read cockpit displays. Muscular exertion and fatigue (arm, shoulder, neck) assessment used electromyography (EMG). Limits in overall reach and throttle and stick movements were measured. RESULTS: Subjects successfully ejected using a two-hand grip under G-stress. Subjects read all displays supporting 5 lb under +6 Gz. Most small-stature subjects could not fully support their heads wearing 3.5 lb helmet during flat spin conditions. CONCLUSIONS: Within the scope of these tests, small-stature subjects demonstrated the strength to safely initiate ejection during severe physically-taxing dynamic conditions but had difficulty supporting AHW under -Gx stress. Human factors deficiencies were noted in the areas of torso harness fit, inertia reel placement relative to shoulder width, and the ability maintain a full range of stick motion. PMID- 11211038 TI - Simulated shuttle egress: comparison of two Space Shuttle protective garments. AB - BACKGROUND: In a previous study from our laboratory, we observed carbon dioxide (CO2) accumulation in the helmet of the NASA Launch and Entry Suit (LES) during a simulated emergency egress from the Space Shuttle. Of 12 subjects, 8 were unable to complete the egress simulation with a G-suit inflation pressure of 1.5 psi. The purpose of this report was to compare CO2 accumulation and egress walking time in the new Advanced Crew Escape Suit (ACES) with that in the LES. METHODS: Four male subjects who previously were unable to complete the egress in the LES performed a simulated egress while wearing the ACES with the G-suit inflated to 1.5 psi. The egress simulation consisted of 6 min of seated rest, 2 min of standing, and 5 min of walking on a treadmill at 1.56 m x s(-1) (3.5 mph) and 0% grade. The helmet visor was closed with the subjects receiving 100% oxygen throughout the simulation. Inspired CO2 and walking time were measured. RESULTS: The rate of CO2 accumulation was significantly less (ACES: 0.53 +/- 0.03, LES: 1.07 +/- 0.15 %CO2 x min(-1); p = 0.05) and walk time was greater in the ACES (ACES: 5.0 +/- 0.0, LES: 2.7 +/- 0.2 min; p = 0.002). CONCLUSIONS: Changes in the design of the ACES from the LES resulted in a decreased rate of CO2 accumulation and an improved egress walking time compared with the LES. PMID- 11211039 TI - A questionnaire for the assessment of the multiple dimensions of motion sickness. AB - BACKGROUND: A limited number of attempts have been made to develop a questionnaire that assesses the experience of motion sickness. Further, many available questionnaires quantify motion sickness as a unidimensional construct. METHOD: Exploratory and confirmatory factor analyses of motion sickness descriptors were used to derive and verify four dimensions of motion sickness, which were defined as gastrointestinal, central, peripheral, and sopite-related. These dimensions of motion sickness were then used to construct a motion sickness assessment questionnaire (MSAQ) that was administered to individuals who were exposed to a rotating optokinetic drum. RESULTS: Total scores from the MSAQ correlated strongly with overall scores from the Pensacola Diagnostic Index (r = 0.81, p < 0.001) and the Nausea Profile (r = 0.92, p < 0.001). CONCLUSIONS: The MSAQ is a valid instrument for the assessment of motion sickness. In addition, the MSAQ may be used to assess motion sickness as a multidimensional rather than unidimensional construct. PMID- 11211040 TI - Prevalence of drugs and alcohol in fatal civil aviation accidents between 1994 and 1998. AB - BACKGROUND: The use of drugs and alcohol in aviation is closely monitored by the FAA Office of Aviation Medicine's (OAM's) Civil Aeromedical Institute (CAMI) through the toxicological analysis of specimens from pilots who have died in aviation accidents. METHOD: Frozen specimens received from local pathologists were tested and the results entered into a computer database for future analysis. The data were sorted based on the class of drug, controlled dangerous substance schedules II, and I controlled dangerous substance schedules III-V, prescription drugs, over-the-counter drugs, and alcohol. RESULTS: Specimens from 1683 pilots were analyzed between 1994 to 1998. Controlled dangerous substances, CDS, (schedules I and II) were found in 89 of the pilots analyzed. Controlled dangerous substances (schedules III-V) were found in 49 of the pilots tested. Prescription drugs were found in 240 of the pilots analyzed. Over-the-counter drugs were found in 301 of the pilots analyzed. Alcohol at or above the legal limit of 0.04% was found in 124 pilots. No abused drugs were found in Class 1 air transport fatal pilots. CONCLUSION: This research supports the very low incidence rate of drugs found in the FAA random drug-testing program. Over-the-counter medications are the most frequently found drugs in fatal aviation accidents and many of these drugs could impair a pilot's ability to safely fly an aircraft. This data is helpful to the FAA in developing programs to reduce the usage of dangerous drugs and identify potentially incapacitating medical conditions that may cause an accident. Data collected from this research can be used to evaluate the effectiveness of the FAA drug-testing program. PMID- 11211041 TI - Clinical risk factors for venous thrombosis associated with air travel. AB - BACKGROUND: Recent reports have linked air travel with venous thrombo-embolism (VTE). Risk factors and associated features of this link are poorly understood. We have accumulated clinical data from a relatively large cohort of patients with traveler's thrombosis. METHODS: A total of 86 patients who developed venous thromboembolism within 28 d of flying were questioned concerning traveling habits, medical history (including risk factors for VTE) and characteristics of the index flight. RESULTS: Of the patients, 72% had at least one risk factor for VTE (excluding thrombophilia) prior to their flight. Of interest, 87% of VTE cases occurred following either a return trip or after an outward journey involving long trips made up of sequential flights. In only two cases could no identifiable risk factor or earlier journey be found. Duration of flights ranged from 2 to 30 h. Of responders, 38% presented with chest symptoms; 92% with VTE developed symptoms within 96 h of their flight. CONCLUSION: We conclude that the majority of VTE associated with air travel occur in those with identifiable risk factors prior to their flight, and that sequential flights may increase this risk. PMID- 11211042 TI - Psychiatric considerations in military aerospace medicine. AB - Military aerospace medicine requires a psychiatric selection and certification process that determines not only the absence of significant mental disorders, but also the presence of positive qualities in the realms of motivation, ability and stability: not all normal people are fit to fly. Other issues of aerospace psychiatry involve maintenance of mental resilience and hardiness during a flying career, aeromedical decisions about when to remove from flight duties and when to return, criteria for waivers for psychiatric conditions, use of medications for treatment of psychiatric symptoms, questions of substance abuse, and research in such areas as genetics. This report reviews the basis for military aerospace psychiatry, primarily as practiced in the United States Air Force (USAF), and presents some of its underlying principles as they apply to clinical situations. PMID- 11211043 TI - Malnutrition, urocanic acid, and sun may interact to suppress immunity in sojourners to high altitude. AB - Irradiation of skin by ultraviolet radiation in mice and humans leads to a suppression of cell-mediated immunity. This process is initiated when one of the photoreceptors in skin, trans-urocanic acid, is photoisomerized to cis-urocanic acid, an immunomodulator. High levels of L-histidine, histamine, and trans urocanic acid are found in humans and animals when they are protein malnourished. Mice fed on an elevated L-histidine diet have more trans-urocanic acid in the skin and are more susceptible to UV-induced immune suppression. Sojourners to high altitudes are malnourished, suffer protein catabolism, are exposed to sun, and often acquire infectious diseases. There is evidence that sunscreens may not adequately protect the immune system. Furthermore, UV intensity increases with altitude. We propose a testable hypothesis: UV radiation causes photoimmune suppression in sojourners to high altitude and this allows infectious diseases to develop. The mechanism we propose includes protein malnutrition, high levels of trans-urocanic acid, ultraviolet radiation, formation of cis-urocanic acid, immune suppression, and infection. PMID- 11211044 TI - You're the flight surgeon. 29-yr-old pilot, accompanied by his wife and 6-yr-old boy, each ill with nausea, abdominal cramping and watery diarrhea. PMID- 11211045 TI - Interpretation of pulmonary function testing during hyperbaric oxygen therapy. PMID- 11211046 TI - Outreach and resolutions. PMID- 11211047 TI - Concept of a Neck Protective Device (CNPD). AB - During impact or sudden acceleration, the cervical and thoracic region of the spine of operators of Habitable Mobile Vehicles (HMV) may be exposed to extensive trauma since "whiplash"-type motion typically leads to impairment of a cervical joint. Furthermore, the frequent necessity of supporting added mass above the shoulders (e.g., crash helmet, displays, oxygen mask) can magnify the moment of inertia of the head. This additional mass affects the biomechanics of a Helmet Head-Neck System and determination of the tolerable magnitudes of acceleration which it can undergo. Even if the body of the operator is restrained by seat belts, such acceleration can arise in all three vectors (Gx, Gy, and Gz). The population at risk for injury due to such forces are individuals exposed to forces generated in racing cars, involved in automobile impacts or emergency landing of aircraft, in normal landing on carriers or in piloting of 5th generation fighter planes, and in other aspects of operator activity in HMV. Various methods of fixation of the head to prevent cervical injury are described in the literature: cervical collars, inflated thoracic defensive members, airbags, cervical supports, etc. However, all of these have some deficiencies related either to one-time availability or the restricted range of head motion which they produce. Widely used automatic retaining systems composed of belts with forced pull and airbags, while successful in other regards, do not adequately protect the head and neck of the operators who are chronically exposed to iterated percussion, and other acceleration forces under diverse extreme conditions. PMID- 11211048 TI - Ode to history and celebration of space medicine: 50 years of vision from the AsMA Space Medicine Branch. Aero Medical Association. PMID- 11211049 TI - Dynamic strength capabilities of small-stature females to perform high performance flight tasks. AB - BACKGROUND: Naval Air Warfare Center Aircraft Division investigated the abilities of small-stature females (< or = 120 lb.) to fly under G-stress using the Dynamic Flight Simulator (DFS) and its tactical fight/attack cockpit, displays and controls. The objective was to determine if these individuals possess sufficient upper-body muscular endurance to perform tasks required during fighter-pilot training, aerial combat maneuvers, and failure modes. METHODS: Five female subjects (four small-stature and one medium) participated. DFS tasks featured bombing runs, surface-to-air missile (SAM) avoidance, and single engine failure. Muscular exertion and fatigue (arm, shoulder, neck) were assessed using electromyography. RESULTS: During the most physically taxing simulation (SAM avoidance), flight performance did not significantly degrade over time. No statistically significant increase in muscular fatigue was found during the bombing simulation, though there was some evidence of degraded fine muscle control. Evidence of flexor and extensor muscular fatigue was associated with the single-engine-failure simulation. CONCLUSIONS: Within the scope of these tests, small-stature individuals demonstrated the strength and endurance to safely fly physically strenuous missions. However, a larger subject sample is necessary to increase the statistical power of the results. PMID- 11211050 TI - Can antiglycolipid antibodies present in HIV-infected individuals induce immune demyelination? AB - Of the eight clinically defined neuropathies associated with HIV infection, there is compelling evidence that acute and chronic inflammatory demyelinating polyneuropathy (IDPN) have an autoimmune pathogenesis. Many non-HIV infected individuals who suffer from sensory-motor nerve dysfunction have autoimmune indicators. The immunopathogenesis of demyelination must involve neuritogenic components in myelin. The various antigens suspected to play a role in HIV seronegative IDPN include (i) P2 protein; (ii) sulfatide (GalS); (iii) various gangliosides (especially GM1); (iv) galactocerebroside (GalC); and (v) glycoproteins or glycolipids with the carbohydrate epitope glucuronyl-3-sulfate. These glycoproteins or glycolipids may be individually targeted, or an immune attack may be raised against a combination of any of these epitopes. The glycolipids, however, especially GalS, have recently evoked much interest as mediators of immune events underlying both non-HIV and HIV-associated demyelinating neuropathies. The present review outlines the recent research findings of antiglycolipid antibodies present in HIV-infected patients with and without peripheral nerve dysfunction, in an attempt to arrive at some consensus as to whether these antibodies may play a role in the immunopathogenesis of HIV associated inflammatory demyelinating polyneuropathy. PMID- 11211051 TI - Mild hypothermia mitigates post-ischemic neuronal death following focal cerebral ischemia in rat brain: immunohistochemical study of Fas, caspase-3 and TUNEL. AB - Mild hypothermia is considered to have a protective effect during ischemic neuronal cell death. The present study provides experimental evidence for this beneficial role of mild hypothermia using reversible middle cerebral artery occlusion (MCAo) in a Sprague-Dawley (SD) rat model. MCAo was induced in rats for 1 h followed by reperfusion at different periods. Hematoxylin-eosin (HE) staining in normothermic (NT) 37 degrees C and hypothermic (HT) 33 degrees C groups of rats confirmed cerebral infarcts. The mean per cent infarct area was significantly reduced in the HT group of rats. Immunohistochemical analysis was done using anti-Fas and caspase-3 antibodies. The immunohistochemical expression of Fas and caspase-3 was demonstrable as early as 5 h after reperfusion, but the expression pattern maximized at 24 h after reperfusion. The expression of Fas and caspase-3 proteins showed a clear decrease in the HT group over the NT group. In situ detection of DNA fragmentation was done using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling method (TUNEL). TUNEL-positive cells were first observed at 5h after reperfusion and progressively increased by 24h. A higher number of TUNEL-positive cells was found in the NT group, but they were significantly decreased in the HT group. Further, DNA fragmentation was confirmed by size fractionation in agarose gel. These findings demonstrate a positive relation between the expression of Fas, caspase-3 and TUNEL-positive cells. PMID- 11211052 TI - Thiophene, a sulfur-containing heterocyclic hydrocarbon, causes widespread neuronal degeneration in rats. AB - Thiophene is a sulfur-containing heterocyclic hydrocarbon that has been detected in a number of environmental sources as various derivatives. Previous studies with rats have shown that thiophene induces selective degeneration of granule cells in the cerebellum, as observed with methyl mercury. To study the neurotoxicity of thiophene, Wistar rats received daily intramuscular injections of 0.2 mL thiophene for 3 days. Ataxia and convulsions were noted in all animals within 24 h after the final dose. Histologically, multiple foci of necrosis were observed in the cerebellum, predominantly in the granular layer. Neuronal damage was also found in the cerebral cortex, inferior colliculus and inferior olive. These findings suggest that thiophene causes widespread neuronal degeneration in rats and that the regional distribution of brain lesions induced by thiophene is different from that caused by methyl mercury poisoning. PMID- 11211053 TI - Amyloid precursor protein beta-secretase (BACE) mRNA expression in human neural cell lines following induction of neuronal differentiation and exposure to cytokines and growth factors. AB - Recently, a novel amyloid precursor protein beta-secretase (designated BACE) was identified. Because activated microglia and astrocytes play a role in amyloidogenesis in Alzheimer's disease, the constitutive and glial cytokine/growth factor-regulated expression of BACE was studied in human neural cell lines. By reverse transcription-polymerase chain reaction (RT-PCR) analysis, BACE mRNA expression was identified in various human neural and non-neural cell lines. By northern blot analysis, the expression of BACE mRNA composed of five distinct transcripts (>8.0, 7.0, 6.0, 4.4 and 2.6 kb) was elevated markedly in NTera2 teratocarcinoma cells following retinoic acid-induced neuronal differentiation. But the levels of three major BACE mRNA species (7.0, 6.0 and 4.4 kb) were not significantly altered in NTera2-derived neurons, SK-N-SH neuroblastoma or U-373MG astrocytoma following exposure to tumor necrosis factor alpha, interleukin (IL)-1beta, IL-6, interferon-gamma, transforming growth factor beta1, epidermal growth factor, basic fibroblast growth factor, brain-derived neurotrophic factor, dibutyryl cyclic adenosine monophosphate or phorbol 12 myristate 13-acetate. These results indicate that BACE mRNA is expressed constitutively in human neural cells and its expression is upregulated during neuronal differentiation, but it is unlikely to be regulated by activated glia derived cytokines and growth factors. PMID- 11211054 TI - Immunohistochemical analysis of brainstem lesions in infantile spasms. AB - Whether the cerebral or subcortical lesions are involved in the pathogenesis in infantile spasms (IS) remains to be determined. To investigate the functional lesions of the subcortical structures in IS, the brainstem expression of neurotransmitters, neuropeptides and calcium-binding proteins in IS autopsy cases of lissencephaly and of perinatal hypoxic ischemic encephalopathy (HIE/IS) was investigated. The IS patients consisted of four subjects each of lissencephaly and HIE. They suffered from both West and Lennox-Gastaut syndromes. The healthy and disease controls were composed of four subjects without neuromuscular disorders and six cases of HIE (HIE/C), neither of whom had the epileptic syndrome. In these subjects the expressions of tryptophan hydroxylase (TrH), tyrosine hydroxylase (TH), parvalbumin (PV), methionine-enkephalin (ME) and substance P (SP) were immunohistochemically determined in serial sections of the midbrain, pons and medulla oblongata. The immunoreactivity of neurons and neuronal processes for TH was altered in the mesencephalic periaqueductal gray matter, locus ceruleus, and dorsal vagal nucleus in the patients. The HIE/IS cases showed reduced TrH-immunoreactivity in the medullary raphe nuclei. The brainstem auditory tract was poorly discernible on anti-PV immunostaining in the IS patients. The immunoreactivity for ME in the spinal trigeminal nucleus was severely affected in the IS patients, while that for SP was comparatively well preserved. It is suggested that the presence of common brainstem lesions in IS is irrespective of etiologies. It is intriguing that some of the changes seemed to be interrelated with the neurophysiological abnormalities being reported in IS patients. PMID- 11211056 TI - Cerebral vasculitis in chronic mucocutaneous candidiasis: autopsy case report. AB - An autopsy case of chronic mucocutaneous candidiasis (CMCC) is reported here, in which cerebral vasculitis developed in the final stage. A 32-year-old man who had suffered from superficial candidial infection since his childhood was diagnosed as having CMCC. During the past 7 years the patient had developed various associated disorders including insulin-dependent diabetes mellitus (IDDM), common variable immunodeficiency (CVID), candidial esophagitis, multiple digestive tract ulcers and pyothorax. In 1998, at the age of 32, he developed convulsions that were accompanied by impairment of consciousness, and which were temporarily treated with steroid pulsed-medication. Epileptic status associated with widespread cerebral infarctions occurred subsequently, however, and the patient died of sepsis 2 months later. At autopsy, multiple cerebral infarctions and arterial thrombosis were evident. These were histologically proven to be primary vasculitis which was confined solely to the brain, and this was verified by general pathological examination. Thus, some as yet unknown cerebrovascular factors might be involved in the onset of an autoimmune-related vasculitis in patients with a longstanding immunodeficiency state such as CMCC. PMID- 11211055 TI - Convulsive effects of thiophene, a heterocyclic hydrocarbon: behavioral, electrographic and c-Fos immunocytochemical studies. AB - The behavioral, electrographic and histopathological changes induced by the heterocyclic hydrocarbon thiophene were investigated in rats following intramuscular injection of 0.3 mL thiophene for 5 days. Generalized convulsions were noted in 29 out of 34 animals (85%) between 1 and 28 h after the final dose. Electroencephalography revealed that the discharges in the hippocampus and forebrain occurred simultaneously, although epileptic activity emerged more strongly from the hippocampus than from any other region. Neuron damage was detected histologically in the temporal and parietal neocortex, piriform gyrus, amygdaloid nucleus and cerebellar cortex, but not in the hippocampus. In contrast, c-Fos was induced widely in the cerebral cortex and hippocampus, and was most marked in the dentate gyrus. These findings suggest that the hippocampus plays a crucial role in seizure onset following thiophene injection. PMID- 11211057 TI - Brain surface ependymoma. AB - A case of brain surface ependymoma is reported here. A 41-year-old woman presented with weakness of the right upper limb. Magnetic resonance imaging revealed a left fronto-parietal cystic tumor with a calcified mural nodule. Total removal of the tumor was performed. This tumor was located within the surface portion of the fronto-parietal parenchyma and was sharply demarcated from the surrounding brain tissue, and there was no continuity with the ventricles. Histological examination of this tumor showed monotonous proliferation of tumor cells with moderate cellularity and occasional mitoses, forming true ependymal rosettes and perivascular pseudorosettes with fibrillary background. A clear cell component resembling oligodendroglioma was partly noted. The tumor cells showed positive immunoreaction for glial fibrillary acid protein and vimentin. PMID- 11211058 TI - Pathology of CAG repeat diseases. AB - Neuronal intranuclear inclusions have become the neuropathological signature of the CAG repeat diseases, although their cytotoxicity is a matter of controversy. It has been demonstrated that the inclusions in dentatorubral-pallidoluysian atrophy (DRPLA) and Machado-Joseph disease (MJD) were immunopositive for several transcription factors such as TATA-binding protein (TBP), TBP-associated factor (TAF(II)130), Sp1, cAMP-responsive element-binding protein (CREB) and CREB binding protein, suggesting that neuronal degeneration in polyglutamine diseases may result from nuclear depletion of transcription factors containing the glutamine-rich domain. It was also revealed that, in the DRPLA brain, expanded polyglutamine stretches were diffusely accumulated in neuronal nucleoplasm. This nuclear pathology involved many neurons in various nervous system regions, such as the cerebral cortex, thalamus, substantia nigra, pontine nuclei, reticular formation and inferior olive, in addition to the previously recognized affected regions. The diffuse nuclear labeling was also detected in MJD, Huntington's disease, and spinal and bulbar muscular atrophy, suggesting that this nuclear pathology may be a characteristic feature and may exert certain influence on certain nuclear functions of many neurons in the CAG repeat diseases. PMID- 11211060 TI - Medical publishing: remembrance of things past and intimations of the future. PMID- 11211059 TI - Interaction of expanded polyglutamine stretches with nuclear transcription factors leads to aberrant transcriptional regulation in polyglutamine diseases. AB - At least eight inherited neurodegenerative diseases are known to be caused by expanded CAG repeats encoding polyglutamine (polyQ) stretches. Although cytotoxicities of expanded polyQ stretches have been suggested, the molecular mechanisms of neurodegeneration remain unclear. The nuclear translocation of mutant proteins containing expanded polyQ stretches has been demonstrated as a prerequisite for the expression of their cytotoxicity. Hypothesizing that nuclear proteins that interact with mutant proteins, particularly, those that bind to the expanded polyQ stretches, are involved in the pathogenetic mechanisms underlying neurodegeneration, nuclear proteins were screened for their capability of binding to expanded polyQ stretches. It was found that expanded polyQ stretches preferentially bind to TAF(II)130, a coactivator involved in cAMP-responsive element-binding protein (CREB)-dependent transcriptional activation. The binding of TAF(II)130 with expanded polyQ stretches strongly suppresses CREB-dependent transcriptional activation, suggesting that interference with transcription due to the binding of expanded polyQ stretches with TAF(II)130 and redistribution of TAF(II)130 are involved in the pathogenetic mechanisms underlying neurodegeneration. PMID- 11211061 TI - Psychological variables in hypertension: relationship to casual or ambulatory blood pressure in men. AB - OBJECTIVE: The evidence linking hypertension with personality or psychological characteristics, such as anger, anxiety, or depression, remains equivocal. This may be due in part to limitations of personality theory, confounding by awareness of hypertension, and/or inherent difficulties in measuring blood pressure. This study was designed to investigate the association between mild hypertension as defined by both ambulatory and casual (clinic) blood pressure measurements and various measures of personality and psychological characteristics. METHODS: We examined this association in a population-based sample of 283 men between the ages of 30 and 60 years from eight work sites in New York City, using an ambulatory blood pressure monitor and controlling for age, race/ethnicity, and body mass index. RESULTS: We found no consistent difference between participants with mild hypertension and those with normal blood pressure on any of the psychological variables assessed, including Type A behavior pattern, state and trait anger, anger expression, anxiety, symptoms of psychological distress, locus of control, or attributional style. Results were not due to the use of antihypertensive medication by some of the participants with hypertension nor to the dichotomization of blood pressure into those with and without mild hypertension. This contrasts with previous findings from this study showing a sizable association of ambulatory blood pressure and hypertension with job strain (a situational measure), age, and body mass index. CONCLUSIONS: These null results suggest that situational, biological, and perhaps behavioral factors are the primary determinants of mild hypertension and that the predictive significance of psychological or dispositional factors is low or negligible in those without overt cardiovascular disease. PMID- 11211062 TI - Coping with breast cancer: patient, spouse, and dyad models. AB - OBJECTIVE: The objectives of this study were 1) to assess similarities and differences between patients with breast cancer and their spouses in terms of coping strategies and adjustment (psychosocial and psychological) to cancer and 2) to investigate the pattern of relationships between the patients' and spouses' coping strategies and between each of these strategies and the patient's adjustment to the illness using three types of models: patient, spousal, and dyadic coping. METHODS: Seventy-three patients with breast cancer and their spouses completed questionnaires that measured distress (Brief Symptom Inventory), psychosocial adjustment, and coping strategies. RESULTS: The patients' distress was greater than their spouses', but a similar level of psychosocial adjustment was reported. The patients used more strategies involving problem-focused coping than their spouses. The use of emotion-focused coping, which included ventilation and avoidance strategies, was highly related to distress and poor adjustment on the part of the patient. The spouses' emotion focused coping and distress were related to that of the patients. Dyad emotion focused coping measures were highly associated with the patients' distress and adjustment. CONCLUSIONS: Spousal and dyad coping are important factors in a patient's adjustment to breast cancer. PMID- 11211063 TI - A randomized, double-blind, placebo-controlled crossover study of the effect of exogenous melatonin on delayed sleep phase syndrome. AB - OBJECTIVE: The effects of exogenous melatonin on sleep, daytime sleepiness, fatigue, and alertness were investigated in 22 patients with delayed sleep phase syndrome whose nocturnal sleep was restricted to the interval from 24:00 to 08:00 hours. This study was a randomized, double-blind, placebo-controlled crossover trial. Subjects received either placebo or melatonin (5 mg) daily for 4 weeks, underwent a 1-week washout period, and then were given the other treatment for an additional 4 weeks. Patients could take the melatonin between 19:00 and 21:00 hours, which allowed them to select the time they felt to be most beneficial for the phase-setting effects of the medication. METHODS: Two consecutive overnight polysomnographic recordings were performed on three occasions: at baseline (before treatment), after 4 weeks of melatonin treatment, and after 4 weeks of placebo treatment. RESULTS: In the 20 patients who completed the study, sleep onset latency was significantly reduced while subjects were taking melatonin as compared with both placebo and baseline. There was no evidence that melatonin altered total sleep time (as compared with baseline total sleep time), but there was a significant decrease in total sleep time while patients were taking placebo. Melatonin did not result in altered scores on subjective measures of sleepiness, fatigue, and alertness, which were administered at different times of the day. After an imposed conventional sleep period (from 24:00 to 08:00), subjects taking melatonin reported being less sleepy and fatigued than they did while taking placebo. CONCLUSIONS: Melatonin ameliorated some symptoms of delayed sleep phase syndrome, as confirmed by both objective and subjective measures. No adverse effects of melatonin were noted during the 4-week treatment period. PMID- 11211064 TI - SF-36: evaluation of quality of life in severe and mild insomniacs compared with good sleepers. AB - OBJECTIVE: Despite many studies, the impact of chronic insomnia on daytime functioning is not well understood. The aim of our study was to detect this impact by evaluating quality of life (QoL) using a validated instrument, the 36 item Short Form Health Survey of the Medical Outcomes Study (SF-36), in three matched groups of severe insomniacs, mild insomniacs, and good sleepers selected from the general population. METHODS: Three matched groups of 240 severe insomniacs, 422 mild insomniacs, and 391 good sleepers were recruited from the general French population after eliminating those with DSM-IV criteria for anxiety or depression. All subjects were asked to complete the SF-36. Scores for each QoL dimension were calculated and compared statistically among the three groups. RESULTS: Severe insomniacs had lower QoL scores in eight dimensions of the SF-36 than mild insomniacs and good sleepers. Mild insomniacs had lower scores in the same eight dimensions when compared with good sleepers. No dimension was significantly more altered than the other. CONCLUSIONS: The mental health status and role of emotional QoL dimensions were worse in severe and mild insomniacs than in good sleepers. This result held even though we screened for psychiatric diseases, which shows a clear interrelation between insomnia and emotional state. General health status was also worse in severe and mild insomniacs than in good sleepers. However, we could conclude only that insomnia was related to a worse health status and not whether it was a cause or consequence of this worse health status. Finally, the degradation of QoL scores was correlated with the severity of insomnia. PMID- 11211065 TI - Alexithymia and polysomnographic measures of sleep in healthy adults. AB - OBJECTIVE: This study examined associations between alexithymia and objective characteristics of sleep (latencies, stages, and amount and patterning of REM sleep) that may contribute to subjective reports of poor sleep quality and impaired dream recall among alexithymic people. METHODS: Fifty healthy, normally sleeping adults from the community completed the 20-item Toronto Alexithymia Scale and slept uninterrupted for one night in the laboratory while polysomnography was conducted. Various measures of sleep latency, sleep stages, and REM sleep-related variables were obtained, and analyses correlated these sleep measures with alexithymia, controlling for age, sex, and level of depressed affect. RESULTS: Higher alexithymia scores were significantly related to increased stage 1 (light) sleep and decreased stage 3/4 (deep) sleep. Alexithymia was unrelated to overall sleep efficiency or percentage of stage 2 sleep. Alexithymia was related to more frequent REM episodes and more stage 1 sleep during and immediately after REM episodes but was unrelated to the absolute amount of REM sleep. Alexithymia was also related to an earlier onset of the first REM episode. CONCLUSIONS: Alexithymia is associated with more light sleep and less deep sleep, which may contribute to subjective reports of poor sleep and increased sleepiness, fatigue, and somatic symptoms. Although alexithymia is not associated with an overall reduction of REM sleep, the increased frequency of episodes of REM that are interrupted and followed by light sleep rather than complete awakenings may contribute to limited dream recall. PMID- 11211066 TI - Plasma levels of neuroactive steroids are increased in untreated women with anorexia nervosa or bulimia nervosa. AB - OBJECTIVE: Animal data suggest that neuroactive steroids, such as 3alpha,5alpha tetrahydroprogesterone (3a,5a-THP), dehydroepiandrosterone (DHEA), and its sulfated metabolite (DHEA-S), are involved in the modulation of eating behavior, aggressiveness, mood, and anxiety. Anorexia nervosa (AN) and bulimia nervosa (BN) are eating disorders characterized by abnormal eating patterns, depressive and anxious symptoms, enhanced aggressiveness, and endocrine alterations. Previous studies reported decreased blood levels of DHEA and DHEA-S in small samples of anorexic patients, whereas no study has been performed to evaluate the secretion of these neuroactive steroids in BN as well as the production of 3alpha,5alpha THP in both AN and BN. Therefore, we measured plasma levels of DHEA, DHEA-S, 3alpha,5alpha-THP and other hormones in patients with AN or BN and explored possible relationships between neuroactive steroids and psychopathology. METHOD: Ninety-two women participated in the study. There were 30 drug-free AN patients, 32 drug-free BN patients, and 30 age-matched, healthy control subjects. Blood samples were collected in the morning for determination of hormone levels. Eating related psychopathology, depressive symptoms, and aggressiveness were rated by using specific psychopathological scales. RESULTS: Compared with healthy women, both AN and BN patients exhibited increased plasma levels of 3alpha,5alpha-THP, DHEA, DHEA-S, and cortisol but reduced concentrations of 17beta-estradiol. Plasma testosterone levels were decreased in anorexic women but not in bulimic women. Plasma levels of neuroactive steroids were not correlated with any clinical or demographic variable. CONCLUSIONS: These findings demonstrate increased morning plasma levels of peripheral neuroactive steroids in anorexic and bulimic patients. The relevance of such hormonal alterations to the pathophysiology of eating disorders remains to be elucidated. PMID- 11211067 TI - Impact of cadaveric organ donation on Taiwanese donor families during the first 6 months after donation. AB - OBJECTIVE: Organ donation is a complex decision for family members of Asian donors. The impact of cadaveric organ donation on both Chinese and Western donor families has not been well investigated within a cultural framework. The purposes of this study were to follow Chinese family members' appraisal of their decision to donate organs, to explore the possible negative and positive impacts of organ donation on their family life, and to determine what help they expected from healthcare providers during the first 6 months after donation. METHODS: Twenty two family members (10 men and 12 women) of cadaveric organ donors who signed consent forms at an organ transplant medical center in Taiwan participated in this project and completed in-depth interviews during the sixth month after donation. RESULTS: Participants were 25 to 56 years old (mean = 48.15 +/- 8.31 years). The type of kinship of the participants included the donor's parents, older sister, and spouse. Subjects reported several negative impacts: worry about the donor's afterlife (86%), stress due to controversy among family members over the decision to donate (77%), and stress due to others' devaluation of the donation (45%). Positive impacts reported by the subjects included having a sense of reward for helping others (36%), having an increased appreciation of life (32%), having closer family relationships (23%), and planning to shift life goals to the study of medicine (9%). Subjects expected the transplant team to provide information about organ recipients (73%), to submit the necessary documents so that family members could receive healthcare payments from the insurance company (68%), to help resolve legal proceedings and settlements associated with accidents (64%), and to not overly publicize their decision to donate (64%). CONCLUSIONS: Although all of the subjects reported that organ donation was the right decision, the decision to donate did not protect Taiwanese donor families from negative psychocognitive bereavement. The impacts of organ donation were affected by the subject's social cultural, spiritual, and legal context and the nature of their bereavement. PMID- 11211068 TI - Psychological stress and antibody response to immunization: a critical review of the human literature. AB - OBJECTIVE: The objective of this review was to evaluate the evidence for the hypothesis that psychological stress influences antibody response to immunization in humans. METHODS: A critical review of the literature was conducted. RESULTS: The evidence supports an association between psychological stress and suppression of humoral immune (antibody) response to immunization. This association is convincing in the case of secondary immune response but weak for primary response. The lack of consistent evidence for a relation with primary response may be attributed to a failure to consider the critical points when stress needs to be elevated in the course of the production of antibody. Lower secondary antibody responses were found among patients with chronically high levels of stress (severe enduring problems or high levels of trait negative affect). These responses were found most consistently among older adults. Lower secondary responses were also found for those reporting acute stress or negative affect, but only in studies of secretory immunoglobulin A antibody in which psychological and antibody measures were linked very closely in time. Health practices did not mediate relations between stress and antibody responses; however, there were indications that elevated cortisol levels among stressed patients could play a role. Evidence also suggests the possible influences of dispositional stress reactivity and low positive affect in the inhibition of antibody production. CONCLUSIONS: The literature supports a relationship between psychological stress and antibody responses to immunizations. The data are convincing in the case of secondary response but weak for primary response. More attention to the kinetics of stress and antibody response and their interrelations is needed in future research. PMID- 11211070 TI - Fibre morphology and soda-sulphite pulping of switchgrass. AB - This paper describes the fibre morphology of switchgrass (Panicum virgatum L.) and its pulping characteristics using sodium hydroxide and a combination of sodium hydroxide and sodium sulphite as the cooking agents. It was found that the fibre length of switchgrass is similar to that of poplar despite its high population of short fibre elements (< 0.2 mm). The switchgrass used in this study had a lignin content comparable to that of poplar, but a particularly high content of extractable materials. The soda pulp from switchgrass showed excellent mechanical properties and showed a great potential as a reinforcement component in newsprint making. PMID- 11211069 TI - Pain and emotion: effects of affective picture modulation. AB - OBJECTIVE AND METHODS: Two experiments examined the impact of viewing unpleasant, pleasant, and neutral photographic slides on cold-pain perception in healthy men and women. In each experiment, participants viewed one of three slide shows (experiment 1 = fear, disgust, or neutral; experiment 2 = erotic, nurturant, or neutral) immediately before a cold-pressor task. Skin conductance and heart rate were recorded during the slide shows, whereas visual analog scale ratings of pain intensity and unpleasantness thresholds and pain tolerance were recorded during the cold-pressor task. RESULTS: Viewing fear and disgust slides decreased pain intensity and unpleasantness thresholds, but only the fear slides decreased pain tolerance. In contrast, viewing erotic, but not nurturant, slides increased pain intensity and unpleasantness threshold ratings on the visual analog scale in men, whereas neither nurturant nor erotic slides altered pain tolerance. CONCLUSIONS: These results are consistent with a motivational priming model that predicts that unpleasant affective states should enhance pain and that pleasant affective states should attenuate it. PMID- 11211071 TI - The effect of low light flux and nitrogen deficiency on the chemical composition of Spirulina sp. (Arthrospira) grown on digested pig waste. AB - Evaluation of the effect of low light flux and nitrogen deficiency on growth and chemical composition of Spirulina sp. (straight filaments strain, SF) in batch cultures utilizing a complex medium containing sea-water supplemented with anaerobic effluents from digested pig waste, was undertaken. Cultivation was carried out either at a light flux of 66 (lower) or 144 micromol photon m(-2) s( 1) (higher), utilizing bench raceways. Biomass concentration (as dry weight) after 12 days of cultivation in the complex medium was similar (P < 0.05) to the one observed in a chemically defined medium (Zarrouk), regardless of the light intensity. Protein content of the biomass in the complex medium was significantly lower (P < 0.05), compared to the Zarrouk medium, regardless of the light flux. However, biomass from the complex medium was enriched in total lipids (28.6%), when cultures were exposed to the lower light flux. On the other hand, the palmitoleic acid percentage of total fatty acids was significantly higher (P < 0.05) at a higher light intensity and a high level of gamma linolenic acid (GLA) as a percentage of total fatty acids was observed (28.13%) in the biomass harvested from the complex medium at the lower light intensity. Finally, polysaccharide content was significantly higher (P < 0.05) at the high light intensity and a very high content of total polysaccharides (28.41%) was observed in the complex medium. PMID- 11211072 TI - Utilization of byproducts from the tequila industry: part 1: agave bagasse as a raw material for animal feeding and fiberboard production. AB - Agave bagasse was successfully separated into fractions that were used in sheep feeding trials. Agave bagasse can be substituted for corn stubble in the sheep's diet which resulted in improved weight gain. Agave bagasse was also processed into long and short fiber fractions with a hammermill and fiberboards of medium and high specific gravities being produced. Medium specific gravity agave fiberboards had moisture and mechanical properties comparable to medium specific gravity fiberboards made using aspen fiber. All high specific gravity agave fiberboards made from short or long fibers were stronger in bending than the ANSI standard for hardboards. PMID- 11211073 TI - Network structures and thermal properties of polyurethane films prepared from liquefied wood. AB - Polyurethane (PU) films were prepared by solution-casting after co-polymerization of liquefied woods (LWs) and polymeric methylene diphenylene diisocyanate (PMDI). The resulting PU films had various [NCO]/[OH] ratios ranging from 0.6 to 1.4 and contained 5.0-16.8% dissolved woody components at the [NCO]/[OH] ratio of 1.0. The crosslink densities of the films with [NCO]/[OH] ratios of 0.6-1.4 increased remarkably with increasing [NCO]/[OH] ratio. Similarly, there were large increases in glass transition temperatures (Tg). These characteristics could be attributed to effective incorporation of PMDI into the LW. The crosslink densities and Tg of the PU films prepared at the [NCO]/[OH] ratio of 1.0 increased because the amounts of dissolved woody components in the films increased. It is concluded that the dissolved woody components acted as crosslinking points in PU network formations. The thermal degradation of the PU films at an [NCO]/[OH] ratio of more than 0.8 or with more than 10.6% dissolved wood started above 262 degrees C under an N2 atmosphere. The thermostability was lost at low crosslink density or with large amount of co-polymerized glycerol structures in the PU networks. PMID- 11211075 TI - Evaluation of the transformation of organic matter to humic substances in compost by coupling sec-page. AB - Humic acids (HAs) from soil and compost at the beginning (S0) and at the end of the stabilization process after 130 days (S130) have been fractionated by coupling size exclusion chromatography (SEC) and polyacrylamide gel electrophoresis (PAGE). Preparative quantities of HA fractions (HAFs) with different molecular sizes (MSs) and exactly defined electrophoretic mobility (EMs) have been obtained from all samples and the HAFs weight content has been studied. A high degree of similarity in HAFs weight content between soil HA and a stabilized compost HAs130 has been observed. Such data seem to be reliable for monitoring the evolution of the compost organic matter to humic substances for their agricultural uses. PMID- 11211074 TI - Aspergillus niger absorbs copper and zinc from swine wastewater. AB - Wastewater from swine confined-housing operations contains elevated levels of copper and zinc due to their abundance in feed. These metals may accumulate to phytotoxic levels in some agricultural soils of North Carolina due to land application of treated swine effluent. We evaluated fungi for their ability to remove these metals from wastewater and found Aspergillus niger best suited for this purpose. A. niger was able to grow on plates amended with copper at a level five times that inhibitory to the growth of Saccharomyes cerevisiae. We also found evidence for internal absorption as the mechanism used by A. niger to detoxify its environment of copper, a property of the fungus that has not been previously exploited for metal bioremediation. In this report, we show that A. niger is capable of removing 91% of the copper and 70% of the zinc from treated swine effluent. PMID- 11211076 TI - Production of ethanol and xylitol from corn cobs by yeasts. AB - Saccharomyces cerevisiae and Candida tropicalis were used separately and as co culture for simultaneous saccharification and fermentation (SSF) of 5-20% (w/v) dry corn cobs. A maximal ethanol concentration of 27, 23, 21 g/l (w/v) from 200 g/l (w/v) dry corn cobs was obtained by S. cerevisiae, C. tropicalis and the co culture, respectively, after 96 h of fermentation. However, theoretical yields of 82%, 71% and 63% were observed from 50 g/l dry corn cobs for the above cultures, respectively. Maximal xylitol concentration of 21, 20 and 15 g/l from 200 g/l (w/v) dry corn cobs was obtained by C. tropicalis, co-culture, and S. cerevisiae, respectively. Maximum theoretical yields of 79.0%, 77.0% and 58% were observed from 50 g/l of corn cobs, respectively. The volumetric productivities for ethanol and xylitol increased with the increase in substrate concentration, whereas, yield decreased. Glycerol and acetic acid were formed as minor by-products. S. cerevisiae and C. tropicalis resulted in better product yields (0.42 and 0.36 g/g) for ethanol and (0.52 and 0.71 g/g) for xylitol, respectively, whereas, the co-culture showed moderate level of ethanol (0.32 g/g) and almost maximal levels of xylitol (0.69 g/g). PMID- 11211077 TI - Adapting substrate formulas used for shiitake for production of brown Agaricus bisporus. AB - A pasteurized, non-composted substrate (basal mixture) consisting of oak sawdust (28%), millet (29%), rye (8%), peat (8%), alfalfa meal (4%), soybean flour (4%), wheat bran (9%), and CaCO3 (10%) was adapted from shiitake culture to produce the common cultivated mushroom (brown; portabello), Agaricus bisporus. Percentage biological efficiency (ratio of fresh mushroom harvested/oven-dry substrate weight, %BE) ranged from a low of 30.1% (when wheat straw was substituted for sawdust) to 77.1% for the basal mixture. Special, high gas-exchange bags were required to optimize mycelial growth during spawn run. Our formula may allow specialty mushroom growers to produce portabello mushrooms on a modified, pasteurized (110 degrees C for 20 min) substrate commonly used for shiitake production without the added expense of compost preparation. PMID- 11211078 TI - Biomass steam gasification--an extensive parametric modeling study. AB - A model for steam gasification of biomass was developed by applying thermodynamic equilibrium calculations. With this model, the simulation of a decentralized combined heat and power station based on a dual fluidized-bed steam gasifier was carried out. Fuel composition (ultimate analysis and moisture content) and the operating parameters, temperature and amount of gasification agent, were varied over a wide range. Their influences on amount, composition, and heating value of product gas and process efficiencies were evaluated. It was shown that the accuracy of an equilibrium model for the gas composition is sufficient for thermodynamic considerations. Net electric efficiency of about 20% can be expected with a rather simple process. Sensitivity analysis showed that gasification temperature and fuel oxygen content were the most significant parameters determining the chemical efficiency of the gasification. PMID- 11211079 TI - Production of oxalic acid from sugar beet molasses by formed nitrogen oxides. AB - Production of oxalic acid from sugar beet molasses was developed in a series of three reactors. Nitrogen oxides formed were used to manufacture oxalic acid in the second and third reactor. Parameters affecting the reaction were determined to be, air flow rate, temperature, the amount of V2O5 catalyst and the concentrations of molasses and H2SO4. The maximum yields in the second and third reactors were 78.9% and 74.6% of theoretical yield, respectively. Also, kinetic experiments were performed and the first-order rate constants were determined for the glucose consumption rate. Nitrogen oxides in off-gases from the final reactor were absorbed in water and concentrated sulphuric acid and reused in the following reactors giving slightly lower yields under similar conditions. In this novel way, it was possible to recover NO(x) and to prevent air pollution. Meanwhile, it was possible to reduce the unit cost of reactant for oxalic acid production. A maximum 77.5% and 74.1% of theoretical yield was obtained by using the absorption solutions with NO(x). PMID- 11211080 TI - Comparative treatability of Moso bamboo and southern pine with CCA preservative using a commercial schedule. AB - The United States Department of Agriculture introduced several bamboo species into the southern United States in the 1920s. One of the species included was Moso bamboo (Phyllostachys pubescens), a species native to China. This species grows well in South Carolina. In rural areas, bamboo splits are frequently used for fences and stakes for supporting crop plants. However, the decay resistance of bamboo is very low. In this study, Moso bamboo splits and southern pine lumber were treated in a commercial wood-treating plant using a full-cell process with Chromated Copper Arsenate (CCA) preservative to target retentions of 4.0 and 6.4kg/m3. Results indicate that bamboo is much more difficult to treat than southern pine. Using the same treatment procedures for southern pine, bamboo could only achieve approximately 22% of the target CCA retention. PMID- 11211081 TI - Effects of various media and supplements on laccase production by some white rot fungi. AB - White rot fungi produce three main extracellular enzymes involved in ligninolysis; laccase, lignin peroxidase and manganese peroxidase. Though all white rot fungi do not produce all three enzymes, laccase occupies an important place in ligninolysis. The present paper reports its production by some white rot fungi; Daedalea flavida, Phlebia brevispora, Phlebia radiata and Polyporus sanguineus under different nutritional conditions. Of the various basal media tested, mineral salts malt extract broth proved to be the best medium for laccase production. Sugarcane bagasse proved to be the best laccase inducer among the various supplements added to different media. PMID- 11211082 TI - Effects of ammonia nitrogen of H2 and CH4 production during anaerobic digestion of dairy cattle manure. AB - A number of researchers have verified the inhibitory effects of elevated H2 concentrations on various anaerobic fermentation processes. The objective of this work was to investigate the potential for using hydrogen gas production to predict upsets in anaerobic digesters operating on dairy cattle manure. In an ammonia nitrogen overload experiment, urea was added to the experimental digesters to obtain increased ammonia concentrations (600, 1,500, or 3,000 mg N/l). An increase in urea concentration resulted in an initial cessation of H2 production followed by an increase in H2 formation. Additions of 600, 1,500, or 3,000 mg N/l initially resulted in the reduction of biogas H2 concentrations. After 24 h, the H2 concentration increased in the 600 and 1,500 mg N/l digesters, but production remained inhibited in the 3,000 mg N/l digesters. Both methane and total biogas production decreased following urea addition. Volatile solids reduction also decreased during these periods. The digester effluent pH and alkalinity increased due to the increased NH4 formed with added urea. Based on these results, changes in H2 concentration could be a useful parameter for monitoring changes due to increased NH3 in dairy cattle manure anaerobic digesters. PMID- 11211083 TI - Assessment of the effect of azo dye RP2B on the growth of a nitrogen fixing cyanobacterium--Anabaena sp. AB - Certain nitrogen fixing cyanobacteria are diazotrophic, which profoundly impacts the aquatic ecosystem chemically and biologically. Although certain types are banned due to their carcinogenicity, azo dyes are commonly used in the dyeing or textile industry. This work investigates the effect of azo dye on the growth of cyanobacteria. Anabaena sp. isolated from the Da Jia Brook is an odor producing, nitrogen fixing cyanobacterium. The growth rates of Anabaena sp. in the media with or without nitrogen source were 3.56 x 10(-2) mg/ml day and 2.44 x 10(-2) mg/ml day, respectively. Anabaena sp. could not use azo dye RP2B as the nitrogen source. Experimental results indicated that the growth of Anabaena sp. was inhibited in the medium containing RP2B. The degree of inhibition increased from 50% to 81% with an increasing concentration of RP2B (0-50 mg/l). The IC-50 (inhibitory concentration) of RP2B on the growth of Anabaena sp. was 5 mg/l (as based on dry weight) or 7 mg/l (as measured by chlorophyll a). PMID- 11211084 TI - Changes in biogas production due to different ratios of some animal and agricultural wastes. AB - The biogas production and some biochemical parameters of anaerobic fermentation at 30 degrees C for 40 days were studied for eight experimental groups of fermentation media, as affected by two factors: (1) the type of the animal waste (sheep waste, S and goat waste, G), and (2) the ratio of waste to olive cake which constitutes four levels (100:0 for S1 and G1; 80:20 for S2 and G2; 60:40 for S3 and G3 and 40:60 for S4 and G4). The results indicated that there was a significant decrease (P < 0.05) in the biogas production with an increase in the proportion of olive cake in place of animal waste. However, there was a significant increase in the biogas production for the S4 treatment compared with G4, reflecting an effect induced by the type of animal waste. The biogas production amounted to (l/kg VS/40 d): 62 (S1), 53 (S2), 49 (S3), 40 (S4), 58 (G1), 50 (G2), 44 (G3) and 25 (G4). The reduction in total solid (TS) weight, volatile solids (VS), neutral-detergent fiber decreased significantly (P < 0.05) with the increase in olive cake proportion in the digester. The reductions in VS were (% in DM): 58.2 (S1), 37.8 (S2), 26.6 (S3), 22.6 (S4), 58.1 (G1), 36 (G2), 33.4 (G3), 14.4 (G4). The rates of energy consumption were (MJ/kg DM/40 d): 15.36 (S1), 10.12 (S2), 7.84 (S3), 6.68 (S4), 14.16 (G1), 9.68 (G2), 8.41 (G3), 3.29 (G4). PMID- 11211085 TI - Enhanced effect of sulfonylurea (SU) in copolymer comprising a sugar moiety and SU derivative as double ligands on insulin secretion from MIN6 cells. AB - Copolymers composed of sulfonylurea (SU) as an antagonist of ATP-sensitive K+ channel and sugar moieties as double ligands were synthesized. Insulin secretion from MIN6 cells (insulinoma cell line) in contact with the copolymers was evaluated. MIN6 cells attached to the poly(N-p-vinylbenzyl-D-maltonamide-co-SU) [P(VMA-co-SU)]-coated dishes were in the more aggregated form as compared to other polymer-coated surfaces. By introducing SU into the sugar bearing homopolymer, an enhanced effect on insulin secretion from MIN6 cells was observed due to the specific interaction between SU ligands and SU receptors on the beta cell membrane. P(VMA-co-SU) composed of SU and non-reducing glucose moieties demonstrated enhanced insulin secretion from MIN6 cells and faster proliferation of MIN6 cells as compared to poly(N-p-vinylbenzyl-D-lactonamide-co-SU) [P(VLA-co SU)] probably owing to the glucose transporters presence on the MIN6 cell membrane. Insulin secretion from MIN6 cells pretreated with diazoxide as an agonist of ATP-sensitive K+ channel was suppressed. PMID- 11211086 TI - Controlled release of vascular endothelial growth factor by use of collagen hydrogels. AB - In vivo profile of vascular endothelial growth factor (VEGF) release from collagen hydrogels was investigated comparing that of hydrogel degradation while angiogenesis induced by the released VEGF was assessed. Collagen sponges were chemically cross-linked with different amounts of glutaraldehyde for various time periods. When 125I-labeled collagen hydrogels incorporating VEGF were subcutaneously implanted into the back subcutis of mice, the hydrogel radioactivity decreased with time, the decrement profile depending on the cross linking conditions. The radioactivity was retained for longer time periods as the glutaraldehyde concentration and cross-linking time increased. Implantation study of collagen hydrogels incorporating 125I-labeled VEGF revealed that the remaining VEGF radioactivity decreased with time and the retention period was prolonged with the decreased hydrogel biodegradation. The slower the hydrogel degradation, the longer the period of VEGF retention. The collagen hydrogel incorporating VEGF induced significant angiogenesis around the implanted hydrogel, in marked contrast to VEGF in the solution form and VEGF-free empty hydrogel. The retention period of angiogenesis became longer with a decrease of the in vivo degradation rate of hydrogels. It is possible that the slower degraded hydrogel achieves a longer period of VEGF release, resulting in prolonged angiogenetic effect. We concluded that in our hydrogel system, biologically-active VEGF was released as a result of in vivo degradation of the hydrogel. PMID- 11211087 TI - Covalent grafting of polythymidylic acid onto amine-containing polystyrene latex particles. AB - The covalent grafting of a 35-base poly(thymidylic) acid (dT35) onto aminated polystyrene latex has been studied. The oligonucleotide was activated by 1,4 phenylene diisothiocyanate (PDC) prior to grafting reaction. The influence of various experimental conditions related either to the medium (pH, ionic strength) or to the latex (nature and surface charge density, presence of adsorbed nonionic surfactant) was studied. Discrimination between covalent grafting and adsorption was achieved by desorbing the non-covalently grafted dT35 induced by consecutive washings with a suitable buffer solution. The amount of covalently grafted oligonucleotide directly correlated to the concentration and accessible functional groups at the particle surface. PMID- 11211089 TI - Evaluation of interfacial properties of hyaluronan coated poly(methylmethacrylate) intraocular lenses. AB - Polymethylmethacrylate intraocular lenses (IOLs) were surface-modified by the linking of a overlayer of hyaluronan. In vitro experiments show that the hydrophilic HA overlayer prevents fibroblasts adhesion and greatly reduces Staphyloccous epidermidis adhesion to the IOL surface. To gain insights into the interfacial properties of untreated and hyaluronan-coated PMMA IOLs, force distance curves were obtained by atomic force microscopy, using standard and modified tips. These measurements allow clear appreciation of the marked difference between the mechanical and chemico-physical properties at the aqueous interface of the uncoated and hyaluronan-coated lenses. PMID- 11211090 TI - Bioactive functionalized polymer of malic acid for bone repair and muscle regeneration. AB - A bioactive poly(beta-hydroxyalkanoate) derived from malic acid was prepared and tested on bone repair and muscle regeneration. This functionalized and hydrolyzable polymer was obtained after several steps, the first one being the anionic copolymerization of three malolactonic acid esters. Chemical modifications were carried out on the terpolymer to turn benzyl-protecting groups into carboxyl groups and allyl groups into sulfonate groups. The resulting polymer bore carboxylate, sulfonate, and sec-butyl pendent groups in 65/25/10 molar proportions and were aimed at interacting with heparan binding growth factors. This polymer did not present any toxic effect in cell viability of HepG2 cells, over a large range of concentrations (0.01-0.25 mgl(-1)). Its ability to improve wound healing was tested in vivo and positive results are reported. Furthermore, the bioactivity of this polymer was evaluated using the regeneration model of Extensor digitorum longus (EDL) rat muscle. The study displayed a significant increase in the muscle regeneration and maturation. PMID- 11211088 TI - A useful marker for evaluating tissue-engineered products: gap-junctional communication for assessment of the tumor-promoting action and disruption of cell differentiation in tissue-engineered products. AB - An in vitro system for evaluating the safety of tissue-engineered products is a convenient because of its rapidity and low cost. On the basis of recent studies, intercellular channels called gap-junctions are considered to play an important role on the tumor-promotion stage during the tumorigenesis induced by polyurethanes. Further, we also demonstrate the significance of the intercellular communication during neuronal cell differentiation. From these results, we propose a survey of the function of the gap-junctional communication as a probable useful marker for evaluating the safety of tissue-engineered products. PMID- 11211091 TI - Recombinant growth hormone delivery systems based on vinylpyrrolidone hydroxyethyl methacrylate copolymer matrices: monitoring optimization by capillary zone electrophoresis. AB - Experimental conditions for the fabrication of two new polymeric devices (i.e. films and slabs) useful for the controlled release of recombinant growth hormone (GH) are given. The release rate is controlled by the resorption profile of the vinylpyrrolidone-hydroxyethyl methacrylate (VP-HEMA) tested systems which is related to the copolymer composition. The suitability of capillary electrophoresis (CE) for following the complete preparation of the different VP HEMA devices is shown. Moreover, CE allows simultaneous monitoring of the controlled release of GH and dissolved polymer during in vitro experiments. From these results, guidelines are given for the fabrication of polymeric devices containing protein as active drug as well as for the correct selection of conditions during in vitro experiments. PMID- 11211092 TI - In vitro evaluation of the biofunctionality of osteoblasts cultured on DegraPol foam. AB - The biofunctionality of osteoblasts cultured on DegraPol-foam, a biodegradable, elastic, and highly porous polyesterurethane-foam, was determined here to examine the possible use of this structure as bone repair material. Osteoblasts from rat tibia and from the cell line (MC3T3-E1) exhibited relatively high attachment and low doubling time that result in a confluent cell multilayer on the surface of the foam. They produced high concentrations of collagen type I and osteocalcin, and expressed increasing alkaline phosphatase activity. Exposure to 1,25 dihydroxy vitamin D (Vit. D) increased dose- and time-dependent alkaline phosphatase activity and osteocalcin concentration, and decreased the level of collagen type I and cell density. Maximal effects of Vit. D on alkaline phosphatase activity (2.2 fold), osteocalcin (1.5 fold), collagen type I (50% reduction), and on cell density (35% reduction) were found at 100 ng Vit. D ml( 1). Osteoblasts cultured on DegraPol-foam in the presence of Vit. D exhibited more spreading and less spindle-like morphology than cells cultured in the absence of Vit. D. Cell ingrowth into the pores of the foam was not affected by Vit. D treatment. Taken collectively, the osteoblasts, capability of responding to Vit. D confirms the osteoblast compatibility of DegraPol-foam and the possible use of this scaffold in the bone healing process. PMID- 11211093 TI - In vitro study of blood-contacting properties and effect on bacterial adhesion of a polymeric surface with immobilized heparin and sulphated hyaluronic acid. AB - The blood-contacting properties and the effect on bacterial adhesion of a material based on polyurethane and poly(amido-amine) (PUPA), both in its native form and with the anticoagulant molecules heparin or sulphated hyaluronic acid (HyalS3.5) electrostatically bonded to its surface, were evaluated and compared in vitro. The presence of the biological molecules on the surface was revealed by a dye test and ATR/FTIR analysis. Bound heparin was found to maintain its physiological action, in terms of thrombin inactivation, as well as did free heparin. Moreover, it reduced the degree of platelet adhesion. On the contrary, bound HyalS3.5 lost its anticoagulant activity, though it reduced platelet adhesion. The number of platelets on both modified surfaces was low. Their shape distribution, as determined by SEM, did not differ significantly on the two modified surfaces or with respect to the bare PUPA surface. HyalS3.5 and heparin also inhibited adhesion of Staphylococcus epidermidis to the material. A possible relationship between the platelet and bacterial adhesion is ascribed to the mediating role of plasma proteins. PMID- 11211094 TI - Thermally reversible VPBA-NIPAM copolymer gels for nucleotide adsorption. AB - A thermosensitive gel matrix was prepared by free radical copolymerization of N isopropylacrylamide (NIPAM) with a boronic acid-carrying monomer (i.e. 4 vinylphenylboronic acid, VPBA). The synthesis of the gel was performed at 70 degrees C in an alcohol-water mixture, using azobisisobutyronitrile and methylenebisacrylamide as the initiator and the crosslinker, respectively. To produce thermosensitive gels with a higher diol-binding affinity, an amino containing comonomer, N-[3-(dimethylamino)propyl]methacrylamide (DMAPM) was included in the gel formation recipe. Thermally reversible VPBA-NIPAM and VPBA DMAPM-NIPAM gels with different swelling properties were obtained by changing the feed concentrations of VPBA and DMAPM. To test the usability of the produced gels as sorbents in nucleotide adsorption, beta-nicotinamide adenine dinucleotide (beta-NAD) was selected as a model biomolecule. Then the adsorption isotherm for beta-NAD was obtained at +4 degrees C in HEPES buffer medium with a pH of 8.5. The support material was in a highly swollen form under these conditions, due to its thermosensitive character. This property was then used to enhance beta-NAD adsorption onto the gel matrix. Equilibrium adsorption capacities up to 70 mg beta-NAD/g dry gel could be achieved with the thermosensitive support prepared with the 12.9 mol% VPBA feed. The gels produced with higher VPBA and DMAPM feed concentrations exhibited higher equilibrium adsorption capacities for beta-NAD. PMID- 11211095 TI - Functional evaluation of poly-(N-p-vinylbenzyl-O-beta-D-galactopyranosyl-[1-4]-D gluconamide)(PVLA) as a liver specific carrier. AB - Hepatocytes express the specific C-type lectin, asialoglycoprotein (ASGP) receptor, on the surface to remove the ligand-bearing proteins from circulation. The specific expression and ligand specificity are thought to be the ideal characters for the target of drug or gene delivery. Various galactose-bearing molecules were synthesized for this purpose. However, the biological or functional interaction of these molecules with the ASGP receptor still remains to be elucidated. In this study. we evaluated the functional ability of synthetic galactose polymer ligand, poly-(N-p-vinylbenzyl-O-beta-D-galactopyranosyl-[1-4]-D gluconamide) (PVLA), to interact with recombinant ASGP receptors using mouse ASGP receptor (mouse hepatic lectin; MHL) gene-transfected CHO cells. PVLA-coated beads bound to and were endocytosed by the whole (MHL-1/-2) ASGP receptor expressing CHO cells like hepatocytes while PVMA (poly-(N-p-vinylbenzyl-O-beta-D glucopyranosyl-[1-4]-D-gluconamide) did not. Interestingly, PVLA-coated beads were also endocytosed by either MHL-1 or MHL-2 alone expressing cells, which are known to be incapable of endocytosing natural ligands. In addition, the endocytosis of PVLA-coated beads by MHL-expressing CHO cells or primary hepatocytes was inhibited only by soluble PVLA but not by the same galactose molecular concentration of soluble asialofetuin. Furthermore, PVLA-coated beads were endocytosed by primary hepatocyte to a significantly higher degree than asialofetuin-coated beads in vitro. These results suggest that PVLA has higher affinity to the ASGP receptor than the natural ligands in blood. Consistently, it was demonstrated that intravenously injected FITC-labeled PVLA but not PVMA drastically accumulated in parenchymal cells of the liver in vivo. Taken together, PVLA exhibiting higher affinity with hepatocytes than natural ligands is thought to be an attractive and practical carrier-ligand for liver targeting. PMID- 11211096 TI - Poly(2-hydroxy ethyl methacrylate)-alkaline phosphatase: a composite biomaterial allowing in vitro studies of bisphosphonates on the mineralization process. AB - We have immobilized the mineralizing agent alkaline phosphatase (AlkP) in a hydrophilic polymer: poly(2-hydroxy ethyl methacrylate) - (pHEMA) - in a copolymerization technique. Histochemical study on polymer sections revealed that AlkP has retained its enzymic activity. The image analysis of sections using a tessellation method showed a lognormal distribution of the area of the tiles surrounding AlkP particles, thus confirming a homogeneous distribution of the enzyme in the polymer. Pellets of pHEMA-AlkP were incubated with a synthetic body fluid containing organic phosphates (beta-glycerophosphate). Mineral deposits with a rounded shape (calcospherites) were obtained in about 17 days. We have investigated the effects of three bisphosphonic pharmacological compounds (etidronate, alendronate and tiludronate) on this system which mimics the mineralization process of cartilage and woven bone. Bisphosphonates at a concentration of 10(-2) M totally inhibited AlkP in solution at a concentration of 10(-4) mg/ml. Inhibition has been reported being due to the chelation of a metal cofactor (Zn2+). Etidronate and alendronate appeared to similarly inhibit the calcospherite deposition onto the pHEMA-AlkP material. Both bisphosphonates possess three sites for the mineral complexion by Ca chemisorbtion. On the other hand, tiludronate having only two sites, was associated with a reduced inhibitory effect on mineralization but larger crystals were obtained. The pHEMA-AlkP material contains an immobilized enzyme in a hydrogel and mimics the physiological conditions of matrix vesicles entrapped within the cartilage (or bone) matrix. It provides an interesting method to study the effects of pharmacological compounds on the mineralization process in bone and cartilage in a non cellular and protein-free model. PMID- 11211097 TI - Clinical long-term in vivo evaluation of poly(L-lactic acid) porous conduits for peripheral nerve regeneration. AB - It was the purpose of this study to evaluate the clinical long-term effects of PLLA degradation in vivo on nerve regeneration in the rat sciatic nerve model. Thirty-one Sprague Dawley rats were utilized. Two groups of animals were selected. The control group of 10 animals received a 12 mm reversed isograft into the right sciatic nerve from 5 donor animals. The experimental group (n = 21) received a 12 mm empty PLLA conduits placed into a 12 mm defect in the right sciatic nerve. The left leg served as an internal control. Walking track analysis was performed monthly through 8 months. At the end of 4 and 8 months, animals in the control isograft and experimental group had the medial and lateral gastrocnemius muscles harvested and weighed for comparison. The midconduit/isograft and the distal nerve in these same animals were harvested and histomorphologically analyzed. Multiple samples were collected and expressed as means +/- standard error. A two-sample t-test and Wilcoxon rank sum test was used to compare the variables. Significance level was set at alpha = 0.05. After Bonferroni correction for multiple testing, a p value of < or = 0.01 was considered statistically significant. Throughout all time periods, the PLLA conduit remained structurally intact and demonstrated tissue incorporation and vascularization. There was no evidence of conduit collapse or breakage with limb ambulation. Moreover, there was no evidence of conduit elongation at 8 months as previously observed with the 75:25 poly(DL-lactic-co-glycolic acid) (PLGA) conduits. The mean absolute value of the sciatic functional index (SFI) demonstrated no group differences from isograft controls measured over the 8 months except at 3 months where the isograft values were higher (p = 0.0379) and at 7 months were the isograft group was significantly lower (p = 0.0115). At 4 and 8 months, the weight of the gastrocnemius muscles of the experimental group was not significantly different from isografts. At 4 months the number of axons/mm2 and nerve fiber density was not significantly different between the isograft control and experimental groups in either the midconduit/isograft or distal nerve. At 8 months the number of axons/mm2 was significantly lower in the isograft compared to the midconduit experimental group (p = 0.006). The number of axons/mm2 in the distal nerve and the nerve fiber density in the midconduit and distal nerve were not significantly different between the two groups. The study confirmed our initial hypothesis that PLLA conduits are a viable scaffold for clinical long-term nerve gap replacement. We are critically aware however that longer evaluation of polymer degradation is warrented. Further studies on these individual nerve components are continuing, with the ultimate goal being the fabrication of a bioactive conduit that meets or exceeds the functional results of isografts. PMID- 11211098 TI - Developing porosity of poly(propylene glycol-co-fumaric acid) bone graft substitutes and the effect on osteointegration: a preliminary histology study in rats. AB - Bioresorbable bone graft substitutes could eliminate disadvantages associated with the use of autografts, allografts and other synthetic materials. We investigated a bioresorbable bone graft substitute made from the unsaturated polyester poly(propylene fumarate) which is crosslinked in the presence of soluble and insoluble calcium filler salts. This compact bone graft substitute material develops porosity in vivo by leaching of the soluble filler salts. In attempt to develop materials whose in vivo porosity can be designed such that implant degradation would occur at a rate that remains supportive of the overall structural integrity of the repairing defect site, we studied the early tissue response upon implantation in a bony defect. Three grout formulations of varying solubilities using slightly soluble hydroxyapatite (HA) and soluble calcium acetate (CA) were evaluated in 3 mm holes made in the anteromedial tibial metaphysis of 200 g Sprague Dawley rats (n = 16 per formulation for a total of 48 animals). Grout formulations cured in situ. Animals from each formulation were sacrificed in groups of 8 at 4 days and 3 weeks postoperatively. Histologic analysis of the healing process revealed improved in vivo osteointegration of bone graft substitutes when a higher loading of calcium acetate was employed. All formulations maintained implant integrity and did not provoke sustained inflammatory responses. This study suggested that the presence of a soluble salt permits in vivo development of porosity of a poly(propylene fumarate) based bone graft substitute material. PMID- 11211099 TI - Bone formation at a rabbit skull defect by autologous bone marrow cells combined with gelatin microspheres containing TGF-beta1. AB - The objective of the present study is to investigate the addition effect of transforming growth factor (TGF)-beta1 on the bone formation at a rabbit skull defect induced by autologous bone marrow (BM). Following application of gelatin microspheres containing TGF-beta1, with or without BM cells to skull bone defects, bone formation at the defect was assessed by soft X-ray, dual energy X ray absorptometry (DEXA), and histological examinations. After implantation for 6 weeks, gelatin microspheres containing 0.05 microg of TGF-beta1 plus 10(6) of BM cells induced bone formation at the 6 mm diameter bone defect. The defect was histologically closed by newly formed bone tissue, whilst both gelatin microspheres containing 0.05 microg of TGF-beta1, and 10(6) and 10(7) of BM cells were ineffective. A DEXA experiment revealed that combination of gelatin microspheres containing TGF-beta1 with BM cells enhanced the bone mineral density at the skull defect to a significantly greater extent than other agents. These findings indicate that a combination of gelatin microspheres containing TGF-beta1 enabled BM cells to enhance the osteoinductive ability, resulting in bone formation even at the cell number at which BM cells alone were ineffective. PMID- 11211100 TI - Cytoskeletal interactions determine the electrophysiological properties of human EAG potassium channels. AB - The electrophysiological properties of ether a go-go (EAG) potassium channels are modified during the cell cycle when they are expressed in heterologous systems. In Chinese hamster ovary (CHO) mammalian somatic cells we found that the cell cycle-dependent modulation of human EAG (hEAG) channels occurs during the M phase. This modulation has three components: reduction in current density, increased sensitivity to block by intracellular sodium, and increased selectivity for potassium ions. In this work, these three properties have been used to define the mitotic phenotype of EAG currents. The signaling pathway leading to such changes of channel properties is unknown. We tested the hypothesis that cytoskeletal interactions might affect the electrophysiological changes observed during the cell cycle. The disruption of actin filaments induces a significant increase in current density, without inducing the cell-cycle-related phenotype. In contrast, disturbance of the microtubules, achieved by pharmacological means or by mechanical excision of the membrane patch, does induce the cell-cycle related phenotype. Our results demonstrate that hEAG channels establish complex interactions with cytoskeletal elements, and that these interactions strongly influence the properties of the channels. We also conclude that the electrophysiological changes observed during the cell cycle are most likely due to reorganization of the cytoskeleton during the G2/M transition. PMID- 11211101 TI - Quartz glass pipette puller operating with a regulated oxy-hydrogen burner. AB - Quartz glass electrodes are superior to conventional glass electrodes for low noise recording. They have better electrical characteristics and hydrophobic surfaces which resist creeping of salt solutions. We used oxy-hydrogen heating with program-controlled gas pressure to melt quartz glass capillaries. Usually, the relative wall thickness (the quotient of the outer and inner diameters do/di) of capillaries is, at best, maintained up to the electrode tip. If tips with thicker walls can be produced, coating and other surface treatments can be avoided. We found that programmed heating periods without pull allowed an fivefold increase of do/di in the tip region. Since do/di is inversely proportional to input capacity, the recording noise was minimized and became insignificant relative to amplifier and holder noise. A sample patch-clamp recording is shown. PMID- 11211102 TI - Modulation of recombinant T-type Ca2+ channels by hypoxia and glutathione. AB - T-type Ca2+ channels are expressed in a wide variety of central and peripheral neurons and play an important role in neuronal firing and rhythmicity. Here we examined the effects of hypoxia on the recently cloned T-type Ca2+ channel alpha1G, alpha1H and alpha1I subunits, stably expressed in HEK 293 cells. In cells expressing the human alpha1H or the rat alpha1I subunit, Ca2+ channel currents were inhibited reversibly by hypoxia (PO2<110 mm Hg). The degree of inhibition was more marked in cells expressing the a1H subunit. This hypoxic inhibition was not voltage dependent. In cells expressing the rat alpha1G subunit, hypoxia caused no detectable reduction in Ca2+ channel activity. Regardless of the channel type examined, hypoxia was without effect on the kinetic properties of the Ca2+ current (activation, inactivation and deactivation) or on steady-state inactivation. Ca2+ current through the alpha1H subunit was enhanced by the reducing agent reduced glutathione (GSH; 2 mM) and inhibited by oxidised glutathione (GSSG; 2 mM). In contrast, Ca2+ current through the alpha1G subunit was unaffected by GSH. In alpha1H cells, neither GSH nor GSSG had any effect on the ability of hypoxia to reduce Ca2+ current amplitudes. Thus, different members of the T-type Ca2+ channel family are differently regulated by hypoxia and redox agents. Hypoxic regulation of the alpha1H subunit appears to be independent of changes in levels of the intracellular redox couple GSSG:GSH. PMID- 11211103 TI - Muscarinic stimulation does not induce rhoA/ROCK-mediated Ca2+ sensitization of the contractile element in chicken gizzard smooth muscle. AB - We have attempted to determine whether muscarinic stimulation induces RhoA/ROCK mediated Ca2+ sensitization of contractions in chicken gizzard smooth muscles. rhoA is a small GTP-binding protein, and ROCK is a rhoA-associated coiled coil forming serine/threonine kinase. The relationship between the cytosolic Ca2+ level ([Ca2+]i) and muscle force in the presence of a high K+ concentration was not different from that in the presence of carbachol. Verapamil inhibited muscle force in proportion to the decrease in [Ca2+]i in both the muscle stimulated with high K+ and that stimulated with carbachol. In addition, Y-27632 (10 microM), a ROCKs inhibitor, had no effect on the contractions. In the alpha-toxin permeabilized muscles, Ca2+ induced a greater contraction in the presence of guanosine 5'-O-(3-thiotriphosphapte) (GTP[gamma-S]), whereas carbachol with GTP was not effective. The GTP[gamma-S]-induced Ca2+ sensitization was completely inhibited by Clostridium botulinum exoenzyme C3. Western blot analysis revealed both rhoA and ROCKII in the muscle extract. In addition, reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed the expression of both ROCKI and ROCKII mRNAs. These results suggest that Ca2+ sensitization in the chicken gizzard is elicited via a rhoA/ROCKs pathway, and that this pathway may be responsible for the augmentation of contraction by GTP[gamma-S] in the permeabilized muscles. If such a pathway does exist, however, carbachol-induced contraction may not be coupled to it, which explains the absence of Ca2+ sensitization in the intact chicken gizzard stimulated by carbachol. PMID- 11211104 TI - Alteration of the membrane lipid environment by L-palmitoylcarnitine modulates K(ATP) channels in guinea-pig ventricular myocytes. AB - Sarcolemmal adenosine 5'-triphosphate-sensitive K+ channels (K(ATP)) are dramatically up-regulated by a membrane phospholipid, phosphatidyl-inositol-4,5 bisphosphate (PIP2). During ischaemia, L-palmitoylcarnitine (L-PC), a fatty acid metabolite, accumulates in the sarcolemma and deranges the membrane lipid environment. We therefore investigated whether alteration of the membrane lipid environment by L-PC modulates the K(ATP) channel activity in inside-out patches from guinea-pig ventricular myocytes. L-PC (1 microM) inhibited KATP channel activity, without affecting the single channel conductance, through interaction with Kir6.2. L-PC simultaneously enhanced the ATP sensitivity of the channel [concentration for half-maximal inhibition (IC50) fell from 62.0+/-2.7 to 30.3+/ 5.5 microM]. In contrast, PIP2 attenuated the ATP sensitivity (IC50 343.6+/-54.4 microM) and restored Ca2+-induced inactivation of KATP channels (94.1+/-13.7% of the control current immediately before the Ca2+-induced inactivation). Pretreatment of the patch membrane with 1 microM L-PC, however, reduced the magnitude of the PIP2-induced recovery to 22.7+/-6.3% of the control (P<0.01 vs. 94.1+/-13.7% in the absence of L-PC). Conversely, after the PIP2-induced recovery, L-PC's inhibitory action was attenuated, but L-PC partly reversed the PIP2-mediated decrease in the ATP sensitivity (IC50 fell from 310+/-19.2 to 93.1+/-9.8 microM). Thus, interaction between L-PC and PIP2 in the plasma membrane appears to regulate K(ATP) channels. PMID- 11211106 TI - The distribution of calcium in toad cardiac pacemaker cells during spontaneous firing. AB - Isolated, spontaneously active pacemaker cells from the sinus venosus region of the toad heart were loaded with the calcium indicator fluo-3. The cells were examined with a confocal microscope to investigate the distribution of calcium during spontaneous activity. Three classes of calcium-related signals were present. First, intense, localised, time-invariant signals were detected from structures distributed across the cell interior. Based on the insensitivity to saponin and the distribution in the cell, these signals appear to arise from fluo 3 located in the sarcoplasmic reticulum and the nuclear envelope. Second, spatially uniform signals from the cytoplasm were present at rest and showed spontaneous increases in [Ca2+]i which propagated along the cell. These Ca2+ transients were uniform in intensity across the diameter of the cell and we could detect no significant delay in the middle of the cell compared to the edges. However, within the nucleus the Ca2+ transient showed a clear delay compared to the cytoplasm. Third, localised, transient increases in [Ca2+]i (Ca2+ sparks) which did not propagate were also detectable. These could be detected both near the surface membrane and in the interior of the cell and reduced in magnitude and increased in duration in the presence of ryanodine. The frequency of firing of Ca2+ sparks significantly increased in the 200-ms period preceding a spontaneous Ca2+ transient. These results suggest that pacemaker cells contain sarcoplasmic reticulum which is distributed across the cell. The Ca2+ transient is uniform across the cell indicating that near-synchronous release of Ca2+ from the sarcoplasmic reticulum is achieved. Ca2+ sparks occur in pacemaker cells though their role in pacemaker function remains to be elucidated. PMID- 11211105 TI - Characterization of the large-conductance Ca-activated K channel in myocytes of rat saphenous artery. AB - We used the patch-clamp method to characterize the BK channel in freshly isolated myocytes from the saphenous branch of the rat femoral artery. Single-channel recordings revealed that the BK channel had a conductance of 187 pS in symmetrical 150 mM KCl, was blocked by external tetraethylammonium (TEA) with a KD(TEA) of approx. 300 microM at +40 mV, and by submicromolar charybdotoxin (CTX). The sensitivity of the BK channel to Ca was especially high (KD(ca) approx. 0.1 microM at +60 mV) compared to skeletal muscle and neuronal tissues. We also investigated the macroscopic K current, which under certain conditions is essentially sustained by BK channels. This conclusion is based on the findings that the macroscopic current activated upon depolarization follows a single exponential time course and is virtually fully blocked by 100 nM CTX and 5 mM external TEA. We made use of this occurrence to assess the voltage and Ca dependence of the macroscopic BK current. In intact myocytes, the BK channel showed a strong and voltage-dependent reduction of the outward current (62% at +40 mV), most likely due to block by intracellular Ba and polyamines. The results obtained from macroscopic and unitary current indicate that approx. 2.5% of the BK channels are active under physiological conditions, sustaining approx. 20 pA of outward current. Given the high input resistance of these cells, few BK channels are required to open in order to cause a significant membrane hyperpolarization, and thus function to limit the contraction resulting from acute increases in intravascular pressure, or in response to hypertensive pathologies. PMID- 11211107 TI - Both linopirdine- and WAY123,398-sensitive components of I K(M,ng) are modulated by cyclic ADP ribose in NG108-15 cells. AB - The "M-like" current in NG108-15 cells has two components carried by different K+ channels: a fast-deactivating component, analogous to IK(M) in sympathetic neurones and carried by KCNQ2/3 channels, and a more slowly deactivating component carried by murine erg1 (merg1) channels. The former is selectively blocked by linopirdine (< or =10 microM), the latter by WAY123,398 (< or =10 microM). Bradykinin (100 nM) inhibited 76% of the KCNQ component of current compared with 12% of the merg component. Cyclic ADP ribose (cADPR, 2 microM), introduced via the patch pipette, caused a rundown of both current components. Acetylcholine (100 microM) inhibited 89% of the KCNQ component of current compared to 34% of the merg component. After 15 min of intracellular dialysis with the cADPR antagonist 8-amino-cADP ribose (100 microM), the inhibition reduced to 40% and 19% and after 30 min it was further reduced to 8% and 5% for the KCNQ currents and merg currents respectively. These data show that both KCNQ and merg currents in NG108-15 cells can be modulated by either bradykinin or M1 muscarinic receptors. The inhibition of the KCNQ current component is more pronounced than that of the merg component. These results suggest that cADPR might be involved in M1-muscarinic inhibition of both KCNQ2/3 and merg1 channels. PMID- 11211108 TI - Cyclooxygenase 2 and neuronal nitric oxide synthase expression in the renal cortex are not interdependent in states of salt deficiency. AB - Neuronal nitric oxide synthase (nNOS) and cyclooxygenase-2 (COX-2) expression in the kidney are localized to the cortical thick ascending limb of the loop of Henle (cTALH), including the macula region, and increase after salt restriction. Because of the similar localization and regulation of nNOS and COX-2 expression, we have examined whether there is a functional interrelationship between the expression of the two enzymes. Male Sprague Dawley rats were fed for 1 week either a low-salt diet (0.02% w/w) which produced moderate increases of nNOS and COX-2 expression, or low salt combined with the angiotensin I converting enzyme inhibitor ramipril (10 mg/kg per day), which produced strong increases of renocortical nNOS and COX-2 expressions. To inhibit nNOS or COX-2 activities, animals received in addition N(G)-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg per day) or rofecoxib (10 mg/kg per day) for 1 week, respectively. L-NAME treatment did not change COX-2 expression and conversely rofecoxib treatment did not change nNOS expression in the kidney cortex under any experimental conditions. L-NAME but not rofecoxib attenuated renin mRNA levels. Rofecoxib markedly reduced renal prostanoid excretion. These findings suggest that under these conditions the control of nNOS and COX-2 gene expression in the macula densa regions of the kidney cortex are not dependent on each other. PMID- 11211109 TI - An intact central nervous system is not necessary for insulin-mediated increases in leg blood flow in humans. AB - Insulin mediates an increase in blood flow in the skeletal muscle. This may be brought about through recruitment of sympathetic vasodilatory nervous activity in the central nervous system (CNS). Insulin may also mediate the vasodilatation by locally acting mechanisms in the skeletal muscle, which in turn could be modulated by vasoconstrictive sympathetic nervous activity. Five men with complete motoric lesions of their cervical spinal cord (SCI) and nine healthy (H) men underwent a hyperinsulinemic (480 mU x min(-1) x m(-2)), euglycemic clamp combined with arterio-venous catheterization of one leg and microdialysis of the thigh muscle. In response to hyperinsulinemia leg blood flow increased similarly in the two groups. Leg glucose extraction and uptake were significantly lower in SCI compared with H. Two hours post clamp, leg glucose uptake rates had not yet returned to basal values. Norepinephrine concentrations in arterial plasma and in the dialysate (reflecting extracellular fluid) did not change in response to insulin in either group, but increased in response to suprapubic bladder tapping in the SCI. Potassium balance measured by microdialysis shifted from a net release to a net uptake in response to insulin, with no difference between SCI and H. In conclusion, the mechanism by which insulin mediates an increase in skeletal muscle blood flow is not due to a CNS recruitment of sympathetic vasodilatory nervous activity. Nor is the insulin-mediated vasodilatation modulated by vasoconstrictive sympathetic nervous activity. The vasodilatation seen in response to hyperinsulinemia is a locally acting mechanism. People with SCI are markedly insulin resistant compared with able-bodied individuals. PMID- 11211110 TI - IK.ACh activation by arachidonic acid occurs via a G-protein-independent pathway mediated by the GIRK1 subunit. AB - The molecular target of arachidonic-acid-derived metabolites, serving as second messengers that activate atrial acetylcholine-activated potassium current (IK.ACh) in addition to G-protein beta/gamma subunits (Gbeta/gamma), is unknown. Co-expression of two isoforms of G-protein-activated, inwardly rectifying potassium channels (GIRKs) in oocytes of Xenopus laevis revealed that these heterologous co-expressed GIRKs, which are responsible for the formation of IK.ACh in the atrium, are activated by arachidonic acid metabolites, like their counterparts in atrial cells. The expression of homooligomeric GIRK1(F137S) and GIRK4wt channels revealed that this activatory mechanism is specific to the GIRKI subunit. Sequestrating available Gbeta/gamma by overexpression of C-betaARK (a Gbeta/gamma binding protein) failed to abolish the activation of GIRK currents by arachidonic acid. From our experiments we conclude that the GIRKI subunit itself is the molecular target for regulation of GIRK channels by arachidonic acid metabolites. PMID- 11211111 TI - Role of receptor protein tyrosine phosphatase alpha (RPTPalpha) and tyrosine phosphorylation in the serotonergic inhibition of voltage-dependent potassium channels. AB - The activity of voltage-gated potassium (Kv) channels can be dynamically modulated by several events, including neurotransmitter-stimulated biochemical cascades mediated by G-protein-coupled receptors. By using a heterologous expression system, we show that activating the 5-HT2C receptor inhibits both Kv1.1 and Kv1.2 channels through a tyrosine phosphorylation mechanism. The major molecular determinants of channel inhibition were identified as two tyrosine residues located in the N-terminal region of the Kv channel subunit. Furthermore, we demonstrate that receptor protein tyrosine phosphatase alpha (RPTPalpha), a receptor protein tyrosine phosphatase, co-ordinates the inhibition process mediated via 5-HT2C receptors. We therefore propose that the serotonergic regulation of human Kv1.1 and Kv1.2 channel activity by the 5-HT2C receptor involves the dual coordination of both RPTPalpha and specific tyrosine kinases coupled to this receptor. PMID- 11211112 TI - Early and long-term changes of equine skeletal muscle in response to endurance training and detraining. AB - Twenty-four 4-year-old Andalusian (Spanish breed) stallions were used to examine the plasticity of myosin heavy chain (MHC) phenotype and the metabolic profile in horse skeletal muscle with long-term endurance-exercise training and detraining. Sixteen horses underwent a training programme based on aerobic exercises for 8 months. Afterwards, they were kept in paddocks for 3 months. The remaining eight horses were used as controls. Three gluteus medius muscle biopsy samples were removed at depths of 20, 40 and 60 mm from each horse before (month 0), during (month 3) and after (month 8) training, and again after 3 months of detraining (month 11). MHC composition was analysed by electrophoresis and immunohistochemistry with anti-MHC monoclonal antibodies. Fibre areas, oxidative capacity and capillaries were studied histochemically. The activities of key muscle enzymes of aerobic (citrate synthase and 3-hydroxy-acyl-CoA-dehydrogenase) and anaerobic (phosphofructokinase and lactic dehydrogenase) metabolism and the intramuscular glycogen and triglyceride contents were also biochemically analysed. Early changes with training (3 months) included hypertrophy of type IIA fibres, a reduction of MHC-IIX with a concomitant increase of MHC-IIA, a rise in the number of high-oxidative fibres and in the activities of aerobic muscle enzymes and glycogen content. Long-term changes with training (8 months) were a further decline in the expression of MHC-IIX, an increase of slow MHC-I, additional increases of high-oxidative fibres, capillary density, activities of aerobic enzymes and endogenous glycogen; intramuscular lipid deposits also increased after 8 months of training whereas the activities of anaerobic enzymes declined. Most of exercise-induced alterations reverted after 3 months of detraining. These results indicate that endurance-exercise training induces a reversible transition of MHC composition in equine muscle in the order IIX-->IIA- >I, which is coordinated with changes in the metabolic properties of the muscle. Furthermore, a dose-response relationship was evident between the duration (in total) of training and the magnitude of muscle adaptations. PMID- 11211113 TI - Involvement of the catecholaminergic system in glucagon-induced thermogenesis in Muscovy ducklings (Cairina moschata). AB - Physiological studies have shown that glucagon is a potential mediator of nonshivering thermogenesis (NST) in birds. The present work was undertaken in order to investigate whether the observed thermogenesis results from a direct action of glucagon on avian thermoregulatory mechanisms or in fact requires the participation of other agents such as catecholamines. Our experiments were performed using cold-acclimated (CA) ducklings which developed muscle NST. A comparison was made with thermoneutral (TN) ducklings of the same age. Our principal results showed that: (1) at ambient temperature (25 degrees C), circulating norepinephrine (NE) was markedly decreased in CA ducklings (-42%), while circulating epinephrine (E) did not undergo any consistent change; (2) in CA and TN ducklings, an intraperitoneal injection of glucagon (360 microg x kg( 1)) was followed after 10 min by prominent lipolysis and a large increase in circulating NE (4- to 6-fold) and E (14- to 17-fold), which was sustained for at least 1 h. The elevation of circulating NE was less pronounced in CA ducklings. The thermogenic action of glucagon in birds is probably indirect and involves at least the mobilization of lipids and sympatho-adrenal stimulation. The changes in peripheral noradrenergic activity during cold acclimation could be associated with adaptive changes leading to NST. PMID- 11211114 TI - Cell volume-sensitive sodium channels upregulated by glucocorticoids in U937 macrophages. AB - Glucocorticoids exert their anti-inflammatory action in part by influencing macrophages. As regulation of macrophage function involves ion channels, the present study was performed to elucidate the influence of glucocorticoids on macrophage ion channel activity. To this end, the effects of corticosteroids on the sodium conductance in human monocytic cells (U937) was studied using whole cell and outside-out patch-clamp techniques. Increasing extracellular osmolarity from 310 to 420 mosmol/kg led to cell shrinkage followed by marked activation of inward whole-cell current from -36+/-2 to -72+/-9 pA (n=13; recorded at -150 mV voltage with CsCl intracellular solution, NaCl extracellular solution) while outward current remained unchanged. The increase of inward current was accompanied by a positive shift of reversal potential and was sensitive to amiloride (100 microM). The activation of inward current by shrinkage was not observed when external sodium was replaced by potassium, indicating that the shrinkage-stimulated conductance is sodium selective. Outside-out single-channel measurements revealed a unitary conductance of 6+/-1 pS (n=5) for the sodium selective amiloride-sensitive current. Pretreating the cells with deoxycorticosterone (100 nM/6 h) markedly upregulated the shrinkage-activated Na+ current. In conclusion, human macrophage-like U937 cells express a sodium selective shrinkage-activated channel which is upregulated by corticosteroids. Activation of the channel may increase cell volume, an effect of glucocorticoids in other cells. PMID- 11211115 TI - Na+-independent proton secretion in MDCK-C11 cells. AB - In this work we studied the proton secretion mechanisms in recently cloned MDCK C11 cells. We measured intracellular pH (pHi) in monolayers grown on permeable filters, using the pH-sensitive probe BCECF and an inverted epifluorescence microscope. The cells have a basal pHi of 7.20+/-0.01 (n=136) and after an acid releasing NH4Cl pulse pHi recovered at a rate (dpHi/dt) of 0.167+/-0.006 pH units/ per minute (n=20). This rate decreased significantly when Na+ was removed from both cell surfaces, and was further reduced when they were both perfused with a solution containing no Na+ and K+. pHi recovery fell again in the presence of concanamycin (at a concentration of 4.6x10(-8) M; a specific inhibitor of the vacuolar H+-ATPase). When Na+ was removed from the apical or the basolateral side, pHi recovery (in pH units per minute) was significantly reduced to 0.099+/ 0.008 (n=11) and 0.086+/-0.01 (n=10), respectively. The Na+-independent mechanism of pHi recovery was significantly inhibited by the presence of 5 x 10(-5) M Schering 28080 (an inhibitor of the H+-K+-ATPase) at the apical side (0.065+/ 0.01 versus 0.099+/-0.008 pH units per minute, P<0.05), but not at the basolateral side (0.072+/-0.01 versus 0.086+/-0.01 pH units per minute). On the other hand, concanamycin inhibited the Na+-independent pHi recovery when applied apically (0.0304+/-0.005 pH units per minute, n=7) and basolaterally (0.025+/ 0.004 pH units per minute, n=7). From these results we conclude that monolayers of MDCK-C11 cells have a Na+/H+ exchanger and a concanamycin-sensitive H+-ATPase on their apical and basolateral membranes; and a K+-dependent, Schering 28080 sensitive H+-K+-ATPase on their apical side. PMID- 11211116 TI - GABA(C) receptors in neuroendocrine gut cells: a new GABA-binding site in the gut. AB - Although GABA(C) receptors play a crucial role in the mammalian central nervous system, their functional expression in peripheral tissues has not yet been studied. Using the gut neuroendocrine tumor cell line STC-1 as a model, we provide first evidence for the functional expression of GABA(C) receptors in the gut: mRNAs of the GABA(C) receptor subunits rho1 and rho2 were detected in STC-1 cells by reverse transcription polymerase chain reaction (RT-PCR). Applying anti rho-antibodies, specific immunostaining for GABA(C) receptors was observed. For functional characterization, the effects of GABA(C) receptor activation on [Ca2+]i and hormone secretion were studied. The selective GABA(C) receptor agonist cis-4-aminocrotonic acid (CACA) induced dose-dependent increases both of [Ca2+]i and of hormone (cholecystokinin) secretion. The stimulatory effects of CACA were antagonized by the GABA(C) receptor blockers (1,2,5,6-tetrahydropyridin 4-yl)methylphosphinic acid (TPMPA) and 3-aminopropyl(methyl)phosphinic acid (3 APMPA). These results demonstrate that GABA(C) receptors play an important role in neuroendocrine gastrointestinal secretion. PMID- 11211118 TI - How to calculate the single-breath nitric oxide diffusing capacity in rabbits. AB - Nitric oxide (NO) is a novel indicator gas for investigating alveolar capillary gas exchange conditions. In clinical practice, pulmonary gas uptake is determined by measuring the single-breath diffusing capacity (DL,NO). Different algorithms are employed to calculate DL,NO. To compare the accuracy of those most commonly used, we performed single-breath experiments on 12 artificially ventilated rabbits. In each animal four manoeuvres, executing breath-holds of 2, 4, 6 and 8 s, were carried out. In each case we administered 55 ml of an indicator gas mixture containing 0.05% NO. Alveolar gas was analysed by respiratory mass spectrometry. The two algorithms for calculating DL,NO based on the conventional solution of the breath-holding equation [Ogilvie et al. (1957) J Clin Invest 36:1 17 and Jones and Meade (1961) Q J Exp Physiol 46:131-143], were compared with the three-equation technique [Graham et al. (1980) IEEE Trans Biomed Eng 27:221-227] as the reference. The deviation between DL,NO calculated from the conventional methods and the reference decreased linearly with increasing duration of NO uptake (deltat). The mean deviations declined from 16.6% (Jones and Meade) or 7.7% (Ogilvie) at deltat=4 s to 5.7% (Jones and Meade) or 2.4% (Ogilvie) at deltat=10 s. The larger mean values are due to the conventional solution where three-tenths of the inflation time is subtracted from deltat. These findings qualify the common prediction that the latter method yields DL,NO values of the highest accuracy. We therefore recommend Ogilvie's procedure if the three equation technique cannot be employed. PMID- 11211119 TI - Influence of exercise intensity on ERK/MAP kinase signalling in human skeletal muscle. AB - The mitogen-activated protein (MAP) kinase pathways have been highlighted as a possible link between exercise and adaptive changes in skeletal muscle. In this study, the effect of exercise intensity on the activation of the ERK/MAP kinase pathway was investigated in human skeletal muscle. One-leg exercise at low (40% maximal oxygen consumption, VO2max for 30 min) and high (75% VO2max for 30 min) intensity resulted in 11.5+8. I-fold and 39.7+/-6.3-fold (mean +/-SEM) increases in ERK1/2 phosphorylation (P<0.001), respectively. The phosphorylation of MEK1/2, the upstream kinase of ERK1/2, increased with exercise intensity (P<0.05) to 2.5+/-0.9 and 4.8+/-1.1 times the basal level at the low and high intensity, respectively. The statistical analysis revealed a systematic difference between basal, low and high intensity exercise levels for both kinases. There was no change in the phosphorylation of either kinase in the non-exercised leg. The phosphorylation of the transcription factor cyclic AMP response element binding protein (CREB), a possible downstream target of the ERK/MAP kinase signalling pathway, was unaffected by exercise. The phosphorylation of ERK1/2 was significantly higher in purified freeze-dried compared to crude wet muscle after exercise, whereas the opposite pattern was observed for CREB. In conclusion, phosphorylation of ERK1/2 and MEK1/2 increases in an exercise intensity-dependent manner in human skeletal muscle and this seems to originate in the muscle fibres themselves. PMID- 11211120 TI - Potential-dependent steady-state kinetics of a dicarboxylate transporter cloned from winter flounder kidney. AB - The two-electrode voltage-clamp technique in combination with tracer uptake experiments was used to investigate the dependence of dicarboxylate transport kinetics on membrane potential in Xenopus laevis oocytes expressing the flounder renal high-affinity-type sodium dicarboxylate cotransporter (fNaDC-3). Steady state succinate-dependent currents in the presence of Na+ were saturable with an apparent affinity constant for succinate, K0.5,succ, of 60 microM. K0.5,succ was independent of membrane potential, suggesting succinate binding at the surface of the fNaDC-3 protein. The maximal succinate-dependent current, deltaImax, increased with hyperpolarization, suggesting that the empty carrier may translocate net charge. Succinate-induced currents showed sigmoidal dependence on Na+ concentration, and K0.5,Na+ decreased with hyperpolarization, suggesting Na+ binding in an ion well. Lowering the external Na+ concentration to 20 mM increased K0.5,succ approximately threefold. Succinate-induced currents were inhibited by Li+ with an Ki,Li+ of approximately 0.5 mM, and a Hill coefficient of below unity indicating the interaction of one Li+ ion with an inhibitory site at fNaDC-3. PMID- 11211117 TI - Effects of anisotropy on the development of cardiac arrhythmias associated with focal activity. AB - The anisotropy that normally exists in the myocardium may be either enhanced in peri-infarction zones by loss of lateral cell connections or reduced by redistribution of gap junctions. To test how the degree of anisotropy affects the development of ectopic focal activity, we carried out computer simulations in which a model of an ectopic focus is incorporated as the central element of a two dimensional sheet of ventricular cells. At low values of intercellular coupling conductance (Gc), the focus region is spontaneously active, but the limited intercellular current flow inhibits propagation. At high Gc, automaticity is suppressed by the loading effects of the surrounding cells. At intermediate Gc, the ectopic activity may propagate into the sheet. In the case of isotropic coupling, the minimum size of the focus region for propagation to occur (in terms of number of collaborating cells within the focus) is as small as approximately ten cells, and this number decreases with increasing anisotropy. Thus, the presence of anisotropy facilitates the development of ectopic focal activity. We conclude that the remodeling that occurs in peri-infarction zones may create a substrate that either facilitates (enhanced anisotropy) or inhibits (reduced anisotropy) the development of cardiac arrhythmias associated with ectopic focal activity. PMID- 11211121 TI - Inwardly rectifying K+ channels in the basolateral membrane of rat pancreatic acini. AB - Previous studies of the whole-cell K+ conductance suggest the presence of inwardly rectifying K+ channels (Kir) in rat pancreatic acini (RPAs). Here we investigate the properties of Kir of RPAs using patch-clamp techniques. The whole cell current-to-voltage relationship of freshly isolated RPAs was steeper for inward currents than for outward currents when the extracellular K+ concentration ([K+]o) was raised. With a high [K+]o (145 mM), external application of Ba2+ and Cs+ blocked the inward K+ current in a voltage-dependent manner. The apparent IC50 of Ba2+ was 8.5+/-1.9 microM and 1.1+/-0.2 microM at -70 mV and -130 mV, respectively (n=5). The IC50 of Cs+ was 3.5+1.1 mM and 0.2+0.1 mM at -60 mV and 120 mV, respectively (n=4). Application of Ba2+ (0.1 mM) to the extracellular solution reversibly depolarized RPAs from -43+1.1 mV to -37+/-1.2 mV (n=20). In the cell-attached configuration with 145 mM KC1 in the pipette solution, we observed inwardly rectifying channels with a high open probability (PO) of 0.85+/ 0.02 (n=6) and a slope conductance (Gs) of 30+/-2.8 pS (n=13). The same type of channel was observed in the outside-out patch. We could also observe a very small conductance K+ channel which was resistant to 0.1 mM Ba2+ and did not show inward rectification (n=11). RT-PCR analysis of RPA confirmed the presence of transcripts for Kir2.1, Kir2.3 and Kir7.1 subfamilies as molecular candidates for the observed channels. The above results demonstrate the presence of Kir channels in the basolateral membrane of the RPA, which may be important for the K+ recycling process during electrolyte secretion as well as for maintaining a hyperpolarized membrane. PMID- 11211122 TI - Conservation of pH sensitivity in the epithelial sodium channel (ENaC) with Liddle's syndrome mutation. AB - Gain-of-function mutations of the epithelial Na+ channel (ENaC) cause a rare form of hereditary hypertension, Liddle's syndrome. How these mutations lead to increased channel activity is not yet fully understood. Since wild-type ENaC (wt ENaC) is highly pH-sensitive, we wondered whether an altered pH-sensitivity of ENaC might contribute to the hyperactivity of ENaC with Liddle's syndrome mutation (Liddle-ENaC). Using Xenopus laevis oocytes as an expression system, we compared the pH-sensitivity of wt-ENaC (alphabetagammarENaC) and Liddle-ENaC (alphabeta(R564stop)gammarENaC). Oocytes were assayed for an amiloride-sensitive (2 microM) inward current (deltaIami) at -60 mV holding potential and cytosolic pH was altered by changing the extracellular pH in the presence of 60 mM sodium acetate. Alternatively, cytosolic acidification was achieved by proton loading the cells using a proton-coupled oligopeptide transporter (PepT-1) co-expressed in the oocytes together with ENaC. Cytosolic but not extracellular acidification substantially reduced deltaIami while cytosolic alkalinisation had a stimulatory effect. This pH-sensitivity was largely preserved in oocytes expressing Liddle ENaC. The inhibition of wt-ENaC and Liddle-ENaC by cytosolic acidification was independent of so-called sodium-feedback inhibition, since it was not associated with a concomitant increase in intracellular Na+ concentration estimated from the reversal potential of deltaIami. In addition C-terminal deletions in the alpha or gamma subunits or in all three subunits of ENaC did not abolish the inhibitory effect of cytosolic acidification. We conclude that ENaC's pH-sensitivity is not mediated by its cytoplasmic C-termini and that an altered pH-sensitivity of ENaC does not contribute to the pathophysiology of Liddle's syndrome. PMID- 11211123 TI - GLUT-4 expression is not consistently higher in type-1 than in type-2 fibres of rat and human vastus lateralis muscles; an immunohistochemical study. AB - In whole muscle homogenates, the glucose transporter-4 (GLUT-4) content is reported to be higher in muscles consisting predominantly of oxidative (type-1) muscle fibres than in muscles consisting predominantly of glycolytic (type-2) fibres. From these findings, it has been deduced that in rat muscle, oxidative fibres have an intrinsically higher level of GLUT-4 protein than glycolytic fibres. No data is available concerning human muscle. Moreover, the fibre-type specific expression of GLUT-4 has not yet been examined directly. In this study, the relative abundance of GLUT-4 protein expression in individual fibres of different types within a muscle was compared directly in immunohistochemical assays. The human vastus lateralis muscle and a selection of rat muscles were studied using a novel GLUT-4 antiserum. It is concluded that the pattern of fibre type-specific GLUT-4 expression differs between human and rats and varies between the different muscles studied, indicating that non-fibre-type-specific factor(s) affect expression of GLUT-4. The observation that within a muscle a fibre-type specific expression of GLUT-4 was observed indicates that fibre-type-specific factors contribute to GLUT-4 expression as well. Thus, it can be postulated that both fibre-type-dependent and fibre-type-independent factors affect GLUT-4 expression. PMID- 11211124 TI - Advantages of smaller body mass during distance running in warm, humid environments. AB - The purpose of this study was to examine the extent to which lighter runners might be more advantaged than larger, heavier runners during prolonged running in warm humid conditions. Sixteen highly trained runners with a range of body masses (55-90 kg) ran on a motorised treadmill on three separate occasions at 15, 25 or 35 degrees C, 60% relative humidity and 15 km x h(-1) wind speed. The protocol consisted of a 30-min run at 70% peak treadmill running speed (sub-max) followed by a self-paced 8-km performance run. At the end of the submax and 8-km run, rectal temperature was higher at 35 degrees C (39.5+/-0.4 degrees C, P<0.05) compared with 15 degrees C (38.6+/-0.4 degrees C) and 25 degrees C (39.1+/-0.4 degrees C) conditions. Time to complete the 8-km run at 35 degrees C was 30.4+/ 2.9 min (P<0.05) compared with 27.0+/-1.5 min at 15 degrees C and 27.4+/-1.5 min at 25 degrees C. Heat storage determined from rectal and mean skin temperatures was positively correlated with body mass (r=0.74, P<0.0008) at 35 degrees C but only moderately correlated at 25 degrees C (r=0.50, P<0.04), whereas no correlation was evident at 15 degrees C. Potential evaporation estimated from sweat rates was positively associated with body mass (r=0.71, P<0.002) at 35 degrees C. In addition, the decreased rate of heat production and mean running speed during the 8-km performance run were significantly correlated with body mass (r=-0.61, P<0.02 and r=-0.77, P<0.0004, respectively). It is concluded that, compared to heavier runners, those with a lower body mass have a distinct thermal advantage when running in conditions in which heat-dissipation mechanisms are at their limit. Lighter runners produce and store less heat at the same running speed; hence they can run faster or further before reaching a limiting rectal temperature. PMID- 11211126 TI - Dietary phosphate and parathyroid hormone alter the expression of the calcium sensing receptor (CaR) and the Na+-dependent Pi transporter (NaPi-2) in the rat proximal tubule. AB - Dietary phosphate (Pi) intake and parathyroid hormone (PTH) are essential regulators of proximal tubular (PT) Pi reabsorption; both factors are associated with adaptive changes in PT apical brush border membrane (BBM) Na/Pi-cotransport activity and specific transporter protein (NaPi-2) content. Urinary Pi excretion is also inversely correlated with luminal Ca2+ concentration ([Ca2+]) both in a PTH-dependent and -independent fashion. A cell-surface, Ca2+(/polyvalent cation) sensing receptor (CaR) has been localized to the PT BBM with unknown function. To investigate whether PTH and/or dietary Pi intake could affect the distribution or the expression of the CaR, we evaluated their effects on rat kidney CaR and the NaPi-2 expression by Western blot analysis and immunofluorescence microscopy. A chronic high-Pi (1.2%) versus low-Pi (0.1%) diet and acute PTH (1-34) infusion significantly reduced the PT BBM expression of both NaPi-2 and CaR proteins. CaR specific immunoreactivity in nephron segments other than the PT was not affected by PTH or Pi intake. These results suggest that reduced renal PT CaR expression by a high-Pi diet and by increased circulating PTH levels could contribute to the local control of PT handling of Ca2+ and Pi. PMID- 11211125 TI - KCNE1 reverses the response of the human K+ channel KCNQ1 to cytosolic pH changes and alters its pharmacology and sensitivity to temperature. AB - Previous studies have shown that heteromultimeric KCNQ1/KCNE1 (KvLQT1/minK) channels and homomultimeric KCNQ1 (KvLQT1) channels exhibit different current properties, e.g. distinct kinetics and different sensitivities to drugs. In this study we report on the divergent responses to internal pH changes and further characterize some of the current properties of the human isoforms of KCNQ1 and KCNE1 expressed in Chinese hamster ovary (CHO) cells or Xenopus laevis oocytes. Decreasing the bath temperature from 37 degrees C to 20 degrees C increased the half-activation time by a factor of 5 for KCNQ1/KCNE1 currents (IKs) but by only twofold (not significant) for KCNQ1 currents (IK) in CHO cells. Acidification of cytosolic pH (pHi) increased IKs but decreased 1K whereas intracellular alkalinization decreased I(Ks) but increased IK. pHi-induced changes in intracellular Ca2+ activity ([Ca2+]i) did not correlate with the current responses. At 20 degrees C mefenamic acid (0.1 mM) significantly augmented IKs but slightly decreased IK. It changed the slow activation kinetics of I(Ks) to an instantaneous onset. The form of the current/voltage (I/V) curve changed from sigmoidal to almost linear. In contrast, at 37 degrees C, mefenamic acid also increased I(Ks) but slowed the activation kinetics and shifted the voltage activation to more hyperpolarized values without markedly affecting the sigmoidal shape of the I/V curve. The potassium channel blockers clotrimazole and tetrapentylammonium (TPeA) inhibited I(Ks) with a lower potency than I(K). These results show that coexpression of KCNE1 reversed pH regulation of KCNQ1 from inhibition to activation by acidic pHi. In addition, KCNE1 altered the pharmacological properties and sensitivity to temperature of KCNQ1. The pH dependence of I(Ks) might be of clinical and pathophysiological relevance in the pathogenesis of ischaemic cardiac arrhythmias. PMID- 11211128 TI - A custom-made two-photon microscope and deconvolution system. AB - We describe in detail a custom-built two-photon microscope based on a modified confocal scanhead (Olympus Fluoview) and mode-locked Ti:sapphire laser (Coherent Mira 900). This system has internal detectors as well as external whole-field detection and an electrooptical modulator for blanking the beam on flyback and effecting fast changes in excitation intensity. This microscope can be used in deep, scattering samples for quantitative measurements with a wide range of fluorophores (GFP, fura, calcium green, calcium orange, fluo-3, DiI, DiO, fluorescein, rhodamine), for fluorescent photobleaching recovery and for uncaging. Images obtained with this system can be deconvolved with the Estimation Maximization algorithm using the program XCOSM (freeware available at: http://www.ibc.wustl.edu/bcl/ xcosm/). PMID- 11211127 TI - Changes of the potassium currents in rat aortic smooth muscle cells during postnatal development. AB - This study was designed to investigate the role and regulation of arterial K+ channels during postnatal development. Rat thoracic aortic segments were suspended for isometric tension and resting membrane potential (RMP) recording. Contraction in response to 4-aminopyridine (4-AP) was similar in 4-, 8- and 12 week-old rats but was higher in 1-day-old rats. Contraction in response to tetraethylammonium (TEA) increased after 4 weeks. TEA increased the contractions evoked by noradrenaline in the aorta from 8- and 12-week-old rats but not from 1 day- and 4-week-old rats. RMP did not change during development. Patch-clamp studies of freshly isolated smooth muscle cells from the same aortas bathed in Ca2+-free medium showed a voltage-dependent K+ current (IK) sensitive to 4-AP. This current remained stable at all ages whereas the density of the total IK, recorded in the presence of Ca2+, showed a twofold increase between 4 and 8 weeks. This current was highly sensitive to TEA and charybdotoxin. The binding site density of 125I-labelled charybdotoxin was threefold higher in the membranes of aortas from 12-week-old compared to 4-week-old rats. These results indicate that changes in K+ channel distribution occur in the rat aorta during postnatal development. These are related to an increase in the expression of charybdotoxin sensitive Ca2+-activated K+ channels. PMID- 11211129 TI - A novel brain trauma model in the mouse: effects of dexamethasone treatment. AB - We describe a novel methodological approach for inducing cold lesion in the mouse as a model of human cortical contusion trauma. To validate its reproducibility and reliability, dexamethasone (Dxm) was repeatedly applied to demonstrate possible antioedematous drug effects. Following the induction of anaesthesia with halothane, the dura was exposed via trephination. Using a micromanipulator a pre cooled (-78 degrees C) copper cylinder, 3 mm in diameter, was pressed down to a depth of 1 mm onto the dura for 30 s under microscopic control. The body temperature was held constant at 37 degrees C throughout the procedure. Blood pressure (BP), measured by a modified photosensor-monitored tail-cuff method, and acid-base status were not significantly different when analysed before and after cold lesion and prior to sacrifice. However, there was a marginal mixed respiratory and metabolic acidosis. The antioedematous action of Dxm was studied in four standard pre-and post-treatment paradigms: 2x0.5 mg/kg (II), 2x12.5 mg/kg (III) and 4x6.25 mg/kg (IV: 3x pre-, 1x post-treatment: V: 1x pre-, 3x post treatment). Physiological saline injections served as controls. High doses of Dxm (III-V) significantly attenuated the cold-lesion-induced loss of body mass. Dxm treatment also resulted in a reduction of brain water content (III; P<0.05), and brain swelling (IV; P<0.05) in the lesioned hemisphere, relative to controls. In conclusion, we have characterized a novel cold lesion model in the mouse to mimic traumatic brain injury and the beneficial effect of Dxm treatment on the extent of brain oedema. PMID- 11211130 TI - Effect of internal carotid artery occlusion on vertebral artery blood flow: a duplex ultrasonographic evaluation. AB - The aim of this study was to evaluate the effect of unilateral internal carotid artery occlusion on blood flow volume and blood flow velocities in both vertebral arteries using duplex Doppler ultrasonography in the cervical segment. Forty patients with unilateral extracranial internal carotid artery occlusion confirmed by angiography were studied, and the results were compared with those obtained in 57 age-matched patients in whom cervical duplex ultrasonography showed no abnormalities. We measured the diameter, flow velocities, and blood flow volume in both vertebral arteries, and the side-to-side differences were also calculated. Eleven patients (27.5%) with an occluded internal carotid artery had increased peak systolic velocity in the ipsilateral vertebral artery, and 6 (15%) had increased peak systolic velocity in the contralateral vertebral artery. The mean peak systolic velocity and the mean blood flow volume were statistically greater in the ipsilateral vertebral arteries than in the same-side vertebral arteries of the control group (P < .05). We also detected a mean increase of 14.29% of the net blood flow volume in the vertebral arteries compared with the control group. Patients with extracranial unilateral internal carotid artery occlusion may have a compensatory increase in both the peak systolic velocity and the blood flow volume in both vertebral arteries. PMID- 11211131 TI - Types of neurovascular symptoms and carotid plaque ultrasonic textural characteristics. AB - The aim of this study was to identify the echo morphology and stenosis of carotid plaques that corresponded to ipsilateral asymptomatic status, amaurosis fugax, hemispheric transient ischemic attack, and stroke. One hundred ninety-two plaques (150 patients), producing stenosis in the range of 50% to 99% and associated with various neurovascular manifestations, were studied. These plaques were imaged on duplex scans, and a series of textural features was produced in a computer to distinguish quantitatively their various echo patterns. Amaurosis fugax corresponded to dark, severely stenosed atheromas (90%); hemispheric transient ischemic attack and stroke corresponded to plaques with intermediate echoic characteristics and intermediate stenosis (80%); and asymptomatic status corresponded to bright, moderately stenosed plaques (70%; P < .05). The significance of these findings is discussed. PMID- 11211132 TI - Assessment of endometrial receptivity by transvaginal color Doppler and three dimensional power Doppler ultrasonography in patients undergoing in vitro fertilization procedures. AB - The objective of this study was to investigate the usefulness of transvaginal color Doppler and three-dimensional power Doppler ultrasonography for the assessment of endometrial receptivity. A total of 89 patients undergoing in vitro fertilization procedures were evaluated for endometrial thickness and volume, endometrial morphology, and subendometrial perfusion on the day of embryo transfer. Neither the volume nor the thickness of the endometrium on the day of embryo transfer had a predictive value for conception during in vitro fertilization cycles (P > .05). Patients who became pregnant were characterized by a significantly lower resistance index, obtained from subendometrial vessels by transvaginal color Doppler ultrasonography (resistance index = 0.53 +/- 0.04 versus 0.64 +/- 0.04, pregnant versus not pregnant, respectively; P < .05), and a significantly higher flow index (13.2 +/- 2.2 versus 11.9 +/- 2.4; P < .05), as measured by a three-dimensional power Doppler histogram. No difference was found in the predictive value of scoring systems analyzing endometrial thickness and volume, endometrial morphology, and subendometrial perfusion by color Doppler and three-dimensional power Doppler ultrasonography. The high degree of endometrial perfusion shown by color Doppler ultrasonography and on three-dimensional power Doppler histograms on the day of embryo transfer can indicate a more favorable endometrial milieu for successful in vitro fertilization. PMID- 11211133 TI - Outcome of pregnancy after prenatal diagnosis of umbilical vein varix. AB - Previous studies of umbilical vein varix diagnosed prenatally have been small, and the results have been contradictory. We wanted to determine whether prenatally diagnosed umbilical vein varix is associated with an increased risk of fetal anomalies or poor perinatal outcomes. We identified all cases of fetal intra-abdominal umbilical vein varix diagnosed on the basis of prenatal ultrasonography at Brigham and Women's Hospital between 1988 and 1998. Cases were reviewed to determine the presence of other sonographic findings as well as pregnancy and neonatal outcomes. We identified 25 cases and included those 23 for which follow-up was available. In 11 cases (48%), pregnancies and neonatal outcomes were normal, with full-term delivery, appropriate birth weight, and no evidence of anomalies. Three cases (13%) had preterm deliveries, and 1 had Kell isoimmunization requiring postnatal transfusion. In the remaining 8 cases (35%), structural anomalies were present. One fetus had a chromosomal abnormality (69,XXX). Prenatal diagnosis of fetal umbilical vein varix appears to be associated with a high rate of fetal anomalies. Detection of an umbilical vein varix should prompt a thorough examination of the fetus, including a fetal survey and echocardiogram. Isoimmunization should be ruled out, and consideration of karyotyping should be discussed if other anomalies are present. PMID- 11211134 TI - Variation in fetal femur length with respect to maternal race. AB - We sought to evaluate whether the expected fetal femur length, based on biparietal diameter, varies in second-trimester fetuses with respect to maternal race. The study population was composed of all fetuses scanned from 15 to 20 completed weeks' gestation during a 2-month period (June to August 1998). Maternal race was documented at the time of the ultrasonographic examination. Biparietal diameter and femur length were prospectively documented. The variance from the expected femur length, given the biparietal diameter, was calculated, and the mean variations were compared according to maternal race. The study subgroups were composed of the fetuses of 39 Asian mothers, 31 black mothers, and the first 100 white mothers. The mean values of the variance from the expected fetal femur length by biparietal diameter +/- 1 SD for the various racial groups were as follows: fetuses of Asian mothers, -0.66 +/- 1.64 mm; fetuses of black mothers, 0.88 +/- 1.57 mm; and fetuses of white mothers, 0.13 +/- 1.66 mm (P = .0007). To isolate the differences among the 3 racial groups, the mean values of the variance from the expected femur length by biparietal diameter for the fetuses of Asian and black mothers were compared with the mean value for the fetuses of white mothers (Asian versus white mothers, P = .014; black versus white mothers, P = .026). A significant difference in the mean variance from the expected femur length by biparietal diameter was identified among the fetuses of women in the second trimester with respect to racial group. Less-than-expected femur lengths were noted among the fetuses of Asian mothers, and greater-than expected femur lengths were noted among the fetuses of black mothers, compared with the femurs of fetuses of white mothers. The implications for the use of fetal femur length as a component of the genetic sonogram in patients of various races require further study. PMID- 11211135 TI - Usefulness of echocystography in the study of vesicoureteral reflux. AB - The aim of our study was to assess the usefulness of contrast-enhanced sonography in detecting and staging vesicoureteral reflux in pediatric patients. Forty-nine children between birth and 5 years of age were studied for vesicoureteral reflux. Echocystography with the use of an endovesical signal enhancer was performed first, followed immediately by conventional voiding cystourethrography. The findings obtained by echocystography and voiding cystourethrography were consistent in 89 (90.8%) of 98 ureterorenal units (a ureterorenal unit is 1 kidney with its own ureter). Reflux was demonstrated by voiding cystourethrography in 13 cases; in 9 of these cases diagnosis had also been made by echocystography. Five cases of reflux detected by echocystography were not identified by voiding cystourethrography. With voiding cystourethrography as the standard of reference, sensitivity was 69%; specificity, 94%; positive predictive value, 64%; and negative predictive value, 95%. In conclusion, echocystography is a useful tool for the diagnosis of vesicoureteral reflux. Its ability to detect reflux is similar to that of cystography in cases of high-grade reflux, and it may be an appropriate complementary technique to voiding cystourethrography, because it avoids exposure to radiation. PMID- 11211136 TI - Abdominal three-dimensional power Doppler imaging. AB - Three-dimensional ultrasonic angiography is a new power Doppler ultrasonographic imaging mode that appears to improve the visualization of vascular anatomy in abdominal sonography. This study illustrates the utility of three-dimensional ultrasonic angiography in the abdomen, especially with respect to liver and portal vein anatomy, vascularization of the kidney, and vessels localized in the retroperitoneum. PMID- 11211137 TI - Ultrasonographically guided biopsy of the prostate gland. PMID- 11211138 TI - Sonographic-pathologic correlation of the hyperechoic border of an atypical hepatic hemangioma. PMID- 11211139 TI - Idiopathic diffuse ectasia of the intrahepatic and extrahepatic arteries. PMID- 11211140 TI - Fetal scalp cysts: challenge in diagnosis and counseling. PMID- 11211141 TI - Contrast-enhanced, wide-band harmonic gray scale imaging of hepatocellular carcinoma: correlation with helical computed tomographic findings. AB - We evaluated the usefulness of contrast-enhanced, wide-band harmonic gray scale imaging for the diagnosis of hepatocellular carcinoma and compared it with helical computed tomography. Forty-eight patients with 61 hepatocellular carcinoma lesions were scanned by contrast-enhanced, wide-band harmonic gray scale imaging after an intravenous bolus injection of the contrast agent Levovist. Fifty-seven of the 61 hepatocellular carcinoma lesions showed hypervascular enhancement, and intratumoral vessels could be observed in 40 of the 57 lesions. Helical computed tomography revealed a high-attenuation area in 54 of the 61 lesions, whereas the other lesions showed an equivocal-attenuation area. Contrast-enhanced, wide-band harmonic gray scale imaging is a useful method for diagnosing the vascularity of hepatocellular carcinoma. PMID- 11211142 TI - Detection of hepatocellular carcinomas and dysplastic nodules in cirrhotic liver: accuracy of ultrasonography in transplant patients. AB - The purpose of this study was to assess the usefulness of ultrasonography in the detection of hepatocellular carcinomas and dysplastic nodules in patients with liver cirrhosis. Pretransplantation sonograms in 52 patients with liver cirrhosis who underwent orthotopic liver transplantation were evaluated retrospectively. The numbers of hepatocellular carcinomas and dysplastic nodules were assessed in the explanted liver specimens and compared with pretransplantation ultrasonographic results. Eighteen hepatocellular carcinomas in 16 patients and 20 dysplastic nodules in 11 patients were present in the explanted livers. The size of hepatocellular carcinomas ranged from 0.6 to 5.0 cm (mean, 2.1 cm) in diameter, and that of dysplastic nodules ranged from 0.5 to 1.7 cm (mean, 1.0 cm) in diameter. Pretransplantation ultrasonography enabled detection of 6 of 18 hepatocellular carcinoma and 0 of 20 dysplastic nodule lesions; lesion detection sensitivity for hepatocellular carcinomas and dysplastic nodules was 33% and 0%, respectively. Patient sensitivity and specificity for hepatocellular carcinomas were 38% (6 of 16) and 92% (33 of 36), and those for dysplastic nodules were 0% and 95% (39 of 41), respectively. On the basis of our results, ultrasonography is insensitive for detection of hepatocellular carcinomas and dysplastic nodules in patients with advanced liver cirrhosis. PMID- 11211143 TI - Induction of tumor-reactive cytotoxic T-lymphocytes using a peptide from NY-ESO-1 modified at the carboxy-terminus to enhance HLA-A2.1 binding affinity and stability in solution. AB - NY-ESO-1 is an attractive candidate tumor antigen for the development of immunotherapy for a wide variety of cancers. It is expressed in multiple types of tumors, but its normal tissue distribution is predominantly limited to the testes and ovaries; furthermore, both humoral and cellular immune responses can be mounted against this protein. Three overlapping HLA-A2.1-restricted T-cell epitopes have been identified within NY-ESO-1. In this investigation, the authors evaluated the in vitro immunogenicity of these peptides. From 2 of 12 HLA-A2.1+ patients with metastatic melanoma, peptide-reactive cytotoxic T-lymphocytes were generated using either NY-ESO-1:157-167 or NY-ESO-1:157-165 but not NY-ESO-1:155 163. Because NY-ESO-1:157-165 is a 9 amino acid peptide completely contained within NY-ESO-1:157-167, it seemed likely that this peptide was the minimal determinant, and thus it was selected for continued study. An amino acid substitution of C to V was introduced into NY-ESO-1:157-165 at P9 to attempt to improve its immunogenicity by enhancing its binding affinity to HLA-A2.1 and increasing its stability in solution, because the C residue is readily oxidized, leading to dimerization of the peptide. From 5 of 20 HLA-A2.1+ patients with metastatic melanoma, NY-ESO-1:157-165(165V) stimulated cytotoxic T-lymphocytes in vitro, which recognized peptide-pulsed target cells and HLA-A2.1+ NY-ESO-1+ tumor cells, suggesting that this peptide may be clinically valuable for the treatment of patients with NY-ESO-1+ tumors. PMID- 11211144 TI - Breast cancer in mice: effect of murine MUC-1 immunization on tumor incidence in C3H/HeOuj mice. AB - Mucin-1 (MUC-1), which is overexpressed in more than 90% of human breast cancers, is a potential target for immunotherapy. To develop a mouse model appropriate for the immunotherapy of human cancer, mouse mucin-1 (muc-1) fusion protein, containing ten tandem repeats, was made and used to immunize C3H/HeOuj mice, which supposedly have a high incidence of breast cancer. C3H/HeOuj mice were injected eight times with 5 microg oxidized mannan muc-1-glutathione-S transferase (MMFP) with or without cyclophosphamide, which is used to increase cellular immunity. At 80 age weeks, only 12.1% (4 of 33) mice of the untreated C3H/HeOuj mice had mammary tumors. The reason for the low incidence of breast cancer in these mice is not known, but all the mammary tumors were MUC-1+ breast adenocarcinomas and were transplantable to C3H/HeOuj mice. The incidence was 11.4% (4 of 35) in mice injected with MMFP: 38.2% (13 of 34) in mice given cyclophosphamide; and 14.3% (2 of 14) in mice treated with glutathione-S transferase. That is, cyclophosphamide increased the incidence of mammary tumors, and metastases were found in only these mice. Fewer tumors (6 of 34 or 17.6% compared with 13 of 34 or 38.2% with cyclophosphamide only) occurred in the group immunized with MMFP and cyclophosphamide. Mice immunized with MMFP had high levels of muc-1 antibodies and cellular immune responses (the frequency of the precursor of the cytotoxic Tlymphocyte cell was 1 of 40,000 to 1 of 100,000), which were not found in control groups. The occurrence of muc-1 immunity, particularly the presence of large amounts of anti-mucin-1 antibodies, had no effect on tumor incidence. Thus, the immunization with murine muc-1 reduced the tumor incidence in only cyclophosphamide-treated mice and led to strong muc-1 antibody production and to cellular responses. These findings have implications for human tumor immunotherapy in which strong antibody and weak cellular responses are to be expected and, indeed, have been found. PMID- 11211145 TI - Semiallogeneic cancer vaccines formulated with granulocyte-macrophage colony stimulating factor for patients with metastatic gastrointestinal adenocarcinomas: a pilot phase I study. AB - The authors report the results of a phase I clinical study using semiallogeneic cancer vaccines formulated with granulocyte-macrophage colony-stimulating factor (GM-CSF) to treat patients with metastatic adenocarcinomas of the gastrointestinal tract. A specially engineered cell line, FO1-12, was used to generate semiallogeneic hybrids by fusion with patient-derived tumor cells; the hybrids express HLA class I and II haplotypes derived from both parental cells. For treatment, the vaccine was mixed with GM-CSF, irradiated, and injected intradermally into patients at weekly or biweekly intervals. Vaccinations were associated with minimal or no toxicity and showed that semiallogeneic hybrids formulated with GM-CSF can induce a specific antitumor immune response in some patients, as measured by a delayed-type hypersensitivity response to autologous tumor cells. Because of the simplicity, feasibility, and flexibility of this immunotherapeutic approach, semiallogeneic hybrid vaccines have the potential to be used in the treatment of virtually any type of cancer. PMID- 11211146 TI - Engineering and characterization of a novel fusion protein incorporating B7.2 and an anti-ErbB-2 single-chain antibody fragment for the activation of Jurkat T cells. AB - The provision of the T-cell costimulatory molecule B7 to tumor cells can be an effective way to trigger a tumor-specific cytolytic T-cell response. One way to provide B7 to tumor cells would be to couple an antitumor antibody directly to B7. Such a molecule should target tumors displaying antigen and provide the costimulatory signal to T cells, resulting in the initiation of an antitumor T cell response. To this end, a fusion protein was designed that incorporates a single-chain antibody fragment (scFv) to erbB-2 (Her2/neu), an oncogene product overexpressed by 30% to 50% of breast carcinomas, and the ECD of B7-2 (CD86). This fusion protein, expressed and purified from Pichia pastoris, was shown to retain binding activity to both counter receptors, erbB-2 and CD28. The fusion protein was also shown to target erbB-2-positive tumor cells and to deliver a CD28-specific T-cell costimulatory signal. These results suggest that a fusion protein engineered to target tumor cells and signal T cells for activation may be an effective means of cancer immunotherapy. Further studies should be performed to characterize the fusion protein in erbB-2 tumor-bearing mice for in vivo tumor targeting, biodistribution, and efficacy. PMID- 11211147 TI - Human inflammatory cells within the tumor microenvironment of lung tumor xenografts mediate tumor growth suppression in situ that depends on and is augmented by interleukin-12. AB - The human tumor microenvironment includes a mixture of tumor cells, inflammatory cells, fibroblasts, and endothelial cells, all of which are tethered to an extracellular matrix. It has been difficult to study the dynamic interactions of these cells in human tumors in situ for obvious ethical and logistical considerations that prohibit experimental manipulations of tumors while still in patients. Fresh tissue from human lung tumor biopsy implanted into SCID mice was shown to remain viable, and the histologic appearance of the tumor microenvironment was maintained in the tumor xenografts for at least 3 months. In this study, the authors established that the inflammatory cells within human tumor xenografts can suppress tumor growth, and that this suppression is a result, in part, of endogenously produced interleukin-12 (IL-12) because IL-12 neutralizing antibodies enhance the growth of the tumor xenografts. The tumor inhibitory activity of the inflammatory leukocytes is also enhanced by the local and sustained release of human recombinant IL-12 into the tumor microenvironment from cytokine-loaded biodegradable microspheres. Neither the anti-IL-12 neutralizing antibody nor the delivery of exogenous IL-12 from microspheres had any effect on tumor xenografts in the absence of the inflammatory leukocytes. In conclusion, the inflammatory cells within the tumor microenvironment of human lung tumor xenografts are functional and can suppress tumor growth, and the dynamic effects of the inflammatory cells can be modulated by exogenous cytokines. PMID- 11211148 TI - Low-dose vaccinia virus-mediated cytokine gene therapy of glioma. AB - Recombinant viruses can produce cytokines in tumors mobilizing an immune response to tumor cells. In this study, the authors investigated gene expression, in vivo antitumor efficacy, and safety of attenuated recombinant vaccinia virus (rVV) carrying murine cytokine genes interleukin (IL)-2 (rVV-mIL-2), IL-12 (rVV-mIL 12), and both IL-2 and IL-12 (rVV-2-12) in an athymic nude mice model. Significant tumor inhibition (p < 0.05) was observed in a preestablished subcutaneously implanted C6 glioma model using rVVs at doses ranging from 10(2) to 10(7) plaque forming units (PFU). An antitumor effect did not depend on the dose of the rVV-mIL-2 and rVV-mIL-12 viruses. All constructed rVVs induced a high level of cytokine expression in vitro and in vivo. Most groups injected with high doses of recombinant viruses encoding cytokine genes (10(5) to 10(7) PFU) showed signs of cytokine toxicity, whereas in the low-dose treatment groups (10(2) to 10(3) PFU) toxicity was greatly reduced. The antitumor activity of rVV-mIL-12 was associated with increases in both the percentage and number of natural killer T cells in the spleen. Local detection of interferon-y and tumor necrosis factor alpha was also correlated with tumor growth arrest induced by the treatment. High dose VV control vector per se induced tumor inhibition by activating Mac-1+ cells in blood, but the antitumor effect was less pronounced compared with rVV-carrying cytokine genes (p < 0.05). These results suggest that attenuated recombinant strains of VV at low doses may potentially be efficient vectors for cancer immunotherapy. PMID- 11211149 TI - Meta-analysis to assess the efficacy of interferon-alpha in patients with follicular non-Hodgkin's lymphoma. AB - The authors wanted to determine whether adding interferon-alpha (IFN-alpha) to chemotherapy regimens, in either induction or maintenance settings, provides additional survival benefits in follicular non-Hodgkin's lymphoma (NHL). A meta analysis was performed based on published data from randomized controlled clinical trials involving nine separate study populations. Patients receiving IFN alpha (in either induction or maintenance therapy) had significantly increased 5 year and progression-free survival rates at 3 and 5 years compared with concurrent controls. The advantages of IFN-alpha therapy were most marked in studies using anthracycline-containing induction chemotherapy; in these studies, patients who received IFN-alpha had approximately 20% increased progression-free survival rates compared with controls and a lesser survival advantage. The available literature did not allow a determination of the relative benefit of IFN alpha in induction or maintenance treatments for NHL or a determination of the optimum duration of IFN-alpha treatment. Although questions remain about its optimal use. IFN-alpha appears to prolong survival time in patients with follicular NHL. PMID- 11211150 TI - Phase I trial of intravenous peptide-pulsed dendritic cells in patients with metastatic melanoma. AB - Sixteen patients with metastatic stage IV melanoma were treated with use of intravenous infusions of dendritic cells (DC) derived by incubation of plastic adherent peripheral blood mononuclear cells (PBMC) with IL-4 and GM-CSF for 8 days in serumless AIM-V medium, followed by overnight pulsing with peptides. The tyrosinase368-376 (370D) and gp100(209-217 (210M)) peptides restricted to HLA class I A*0201 each differed from wild type by one amino acid modified to increase HLA binding. Median age was 49, with nine men and seven women. All patients, except one, had visceral disease. Patients received escalating doses of peptide-pulsed DCs at 10e7, 3 x 10e7, and 10e8 cells/dose twice at 2 weeks apart, with toxicity and clinical and immune responses as the principal endpoints. The first infusion of DCs was fresh, and frozen DCs were given for the second infusion of each cycle. Mean DC purity by flow cytometry was 49%, with a mean HLA DR level of 57%, CD86 of 41%, CD58 of 46%, and mean CD14 cells of 0.9%. Toxicity was minimal, with two patients having transient grade III DC-related toxicity. Ten patients received one cycle of treatment and six patients received two cycles of treatment. One patient had a complete remission (CR) of lung and pleural disease after two cycles of DC therapy. Two additional patients had stable disease and two patients had mixed responses. Overall immunity was assessed by recall skin testing with peptides, gamma interferon ELISA assays of peptide specific cytolytic T cell (CTL) stimulated twice with peptide, IL-2, and IL-7 over 24 days, and peptide-specific tetramer assays performed before and after vaccination. Five of 16 patients had an immune response to gp100 or tyrosinase by gamma interferon ELISA assay; four of five were clinically stable or had tumor regression. These data suggest that melanoma antigen peptide-pulsed DC given intravenously are not toxic, and regression or stability of tumor appeared to correlate with the detection of a peptide-specific immune response in the peripheral blood. PMID- 11211151 TI - Phase I pilot trial of the bispecific antibody MDXH210 (anti-Fc gamma RI X anti HER-2/neu) in patients whose prostate cancer overexpresses HER-2/neu. AB - The goal of this study was to evaluate, in patients with prostate cancer, the toxicity profile and biologic activity of the bispecific antibody MDXH210, which has specificity for the non-ligand-binding site of the high-affinity immunoglobulin G receptor (Fc gamma RI) and the extracellular domain of the HER 2/neu proto-oncogene product. Patients with prostate cancer that expressed HER 2/neu were entered into a phase I dose-escalation trial of MDXH210. Patients received an intravenous infusion MDXH210 during a period of 2 h three times per week for 2 weeks and were monitored for toxicity. Pharmacokinetic and pharmacodynamic parameters were measured and included the biologic end points of monocyte-bound MDXH210, cytokine production, and clinical response. Seven patients were treated with MDXH210 doses ranging from 1 to 8 mg/m2. In general, MDXH210 was well tolerated, with only mild infusion-related malaise, fever, chills, and myalgias. No dose-limiting toxic effects were observed. Biologic effects included induction of low plasma concentrations of tumor necrosis factor alpha and interleukin-6 observed immediately after MDXH210 infusion and 70% saturation of circulating monocyte-associated Fc gamma RI with MDXH210 at a dose level of 4 to 8 mg/m2. Five of six patients had stable prostate-specific antigen levels during the course of 40 days or more. Circulating plasma HER-2/neu levels decreased by 80% at days 12 and 29 (p = 0.03 and 0.06, respectively, by the Wilcoxon signed rank test). MDXH210 can be given safely to patients with HER 2/neu-positive prostate cancer in doses of at least 8 mg/m2. At the doses studied, biologic activity was demonstrated and characterized by binding of MDXH210 to circulating monocytes, release of monocyte-derived cytokines, a decrease in circulating HER-2/neu, and short-term stabilization of prostate specific antigen levels. PMID- 11211152 TI - Patients with melanoma metastases at cutaneous and subcutaneous sites are highly susceptible to interleukin-2-based therapy. AB - The authors evaluated the records of 371 patients with metastatic melanoma who received treatment with high-dose bolus interleukin-2. Patients with metastases only at cutaneous or subcutaneous sites had a higher objective response rate (50%) than did patients with metastases at these sites plus visceral sites (14%) or patients with metastases at visceral sites only (13%) (p<0.0001). Five patients with disease at cutaneous or subcutaneous sites plus visceral sites experienced regression only at the cutaneous or subcutaneous sites with progression at the visceral sites. Therefore, in the presence of visceral disease, the response rate at cutaneous or subcutaneous sites was only 17% compared with 50% when disease was at the latter sites only (p<0.001). These data suggest that melanoma lesions at cutaneous or subcutaneous sites are highly susceptible targets to interleukin-2-based therapies, but the presence of visceral disease is associated with a significant inhibition of response at cutaneous or subcutaneous sites. PMID- 11211153 TI - Agranulocytosis and hemolytic anemia in patients with renal cell cancer treated with interleukin-12. AB - Interleukin-12 (IL-12) is a cytokine with effects on immune function and hematopoiesis. In this article, the authors describe two patients with renal cell cancer in whom grade 4 neutropenia and grade 3 hemolytic anemia developed, respectively, during treatment with twice-weekly intravenous recombinant human interleukin-12 (rhIL-12) during a phase 1 trial. The severe neutropenia was associated with bone marrow agranulocytosis and a preponderance of large granular lymphocytes in the peripheral blood, whereas the hemolytic anemia was negative for the Coombs test and associated with splenomegaly. The agranulocytosis and hemolytic anemia persisted after the rhIL-12 was stopped, but both subsequently responded to treatment with cyclophosphamide. steroids, or both. These findings indicate that rhIL-12 can induce unique hematologic toxic effects that can be reversed with immunosuppressive drugs. PMID- 11211154 TI - Effect of surgical insertion on the local shell properties of SILASTIC II silicone gel breast implants. AB - The reasons for the failure of silicone gel breast implants are unclear. One potential failure mechanism is the weakening of the implant shell during its insertion into the breast. Such local weakening could eventually lead to implant failure. We recently reported on the effect of implant surgery on the overall mechanical properties of SILASTIC II gel-filled implants. In the earlier study, the mechanical properties of 34 Dow Corning SILASTIC II gel-filled breast implants from the same manufacturing lot were measured. Twenty of the thirty four implants were not implanted but were evaluated to establish a baseline of control data. The other fourteen lot-matched implants were inserted into a subglandular pocket through an inframammary incision in a cadaver breast and then removed. The experimental augmentation scenario was designed to represent actual breast implantation as closely as possible. The mechanical properties of the anterior and posterior sides of the control implants (not implanted) and explants (implanted in a cadaver) were measured and compared to determine whether differences existed between the explant and control groups. We found that the implantation surgery process did slightly reduce the average tensile strength. Although not as statistically significant, other mechanical properties such as breaking energy and moduli were less for the explants than the controls. The reduction was a relatively small percentage in the context of overall shell properties. Elongation and tear resistance were unaffected. Our findings suggested that the surgical act of implanting a breast implant has a small but detectable weakening effect on the average tensile strength, breaking energy and moduli of the elastomeric shell of the device. The present study is an extension of the previous investigation. Here we have analyzed the explant shell region where the surgeon's fingers forced the implant through the incision. Our results indicate that the implant shell can be locally damaged due to the implantation process. PMID- 11211155 TI - Poly(amino acid) bioadhesives for tissue repair. AB - We report here on poly(amino acid)-based bioadhesives with potential to bond to soft tissues. The systems investigated included homopolymer poly(amino acids), mixtures of poly(amino acids) and amino acids, and blends of different poly(amino acids). Adhesive performance was tested in tension on glass surfaces, chondroitin sulfate surfaces, as well as bovine cartilage surfaces. The amino acid structural units contained acidic, basic, or polar side chains and were found to adhere reasonably well to the surfaces of glass and chondroitin sulfate. The formation of polymer-monomer complexes with the addition of a basic monomer such as L lysine to negatively charged polymers such as poly(L-aspartic acid) and poly(L glutamic acid) was found to result in greater adhesive strength relative to homopolymers. Further improvement in adhesion was observed in blends of poly(L lysine) with polar poly(amino acids) such as poly(L-asparagine). Adhesion on wet cartilage surfaces was the weakest measured but a priming approach designed to form electrostatic or hydrogen bonds appears promising. We believe the strength of the adhesives studied here is based on the ability of their constituent polymers and monomers to form molecular entanglements and crosslinks for load transfer. We also believe hydrogen bonds and electrostatic forces play a role in the adhesion of the systems to the substrates probed in this work. PMID- 11211156 TI - Sustained release of mitomycin-C from poly(DL-lactide) /poly(DL-lactide-co glycolide) films. AB - Mitomycin-C (MMC)-loaded poly(DL-lactide) (PLA)/poly(DL-lactide-co-glycolide) (PLGA) films which have different drug loading capacities and thicknesses were prepared by a solvent-evaporation technique. Degradation and release studies were conducted at 37 degrees C in pH 7.4 phosphate buffered saline. The results showed that both the rate and the percentage of released MMC increased as the glycolide content in the copolymer increased from 10 to 30% (w/w) and the drug load increased from 0.5 to 2 mg MMC per 300 mg of polymer. In contrast, they decreased depending upon increasing film thickness from 80 to 300 microm and polymer molecular weight. It was found that the drug release mechanism is diffusion controlled according to a non-Fickian diffusion mechanism. PMID- 11211157 TI - Design and microstructuring of PDMS surfaces for improved marine biofouling resistance. AB - In this study room temperature vulcanized (RTV) silicone surfaces with designed surface microstructure and well-defined surface chemistry were prepared. Their resistance to marine macrofouling by barnacles Balanus improvisus was tested in field experiments for deducing optimal surface topography dimensions together with a better understanding of macrofouling mechanisms. Polydimethylsiloxane (PDMS) surfaces were microstructured by casting the PDMS pre-polymer on microfabricated molds. The master molds were made by utilizing photolithography and anisotropic etching of monocrystalline silicon wafers. Several iterative casting steps of PDMS and epoxy were used to produce large quantities of microstructured PDMS samples for field studies. The microstructured PDMS surface consisted of arrays of pyramids or riblets creating a surface arithmetic mean roughness ranging from 5 to 17 microm for different microstructure sizes and geometries, as determined by scanning electron microscopy. Chemophysical properties of the microstructured films were investigated by electron spectroscopy for chemical analysis, time-of-flight secondary ion mass spectroscopy and dynamic contact angle measurements. Films were chemically homogeneous down to the submicron level. Hydrophobicity and contact angle hysteresis increased with increased surface roughness. Field tests on the west coast of Sweden revealed that the microstructure containing the largest riblets (profile height 69 microm) reduced the settling of barnacles by 67%, whereas the smallest pyramids had no significant influence on settling compared to smooth PDMS surfaces. The effect of dimensions and geometry of the surface microstructures on the B. improvisus larvae settling is discussed. PMID- 11211158 TI - Synthesis, analytical characterization, and osteoblast adhesion properties on RGD grafted polypyrrole coatings on titanium substrates. AB - The covalent attachment of an Arg-Gly-Asp (RGD) containing peptide to polypyrrole(PPy)-coated titanium substrates has been investigated in order to develop a bioactive material of potential use in orthopedic fields. Polypyrrole has been employed as the coating polymer because of its suitability to be electrochemically grown directly onto metallic substrates of different shapes, leading to remarkably adherent films. The synthetic peptide Cys-Gly-(Arg-Gly-Asp) Ser-Pro-Lys, containing the cell-adhesive region of fibronectin (RGD), has been grafted to the polymer substrate via the cysteine residue using a procedure recently developed in the authors laboratory. The effectiveness of grafting was monitored by X-ray photoelectron spectroscopy (XPS), which assessed the presence of the peptide grafted onto the polymer surface exploiting the cysteine sulfur as target element. Neonatal rat calvarial osteoblasts were attached to RGD-modified PPy-coated Ti substrates at levels significantly greater than on unmodified PPy coated Ti and glass coverslip substrates. PMID- 11211159 TI - The effect of fluorinated surface modifying macromolecules on the surface morphology of polyethersulfone membranes. AB - Polyethersulfone (PES) has been recently adopted for membrane materials in applications such as ultrafiltration and haemodialysis. As a biomaterial, the factors which affect the blood compatibility of PES membranes include surface energetics, hydrophobicity, and surface morphology. Surface fluorination of materials has been found to create surfaces with improved blood compatibility and chemical stability. One novel approach to generating fluorinated polymer surfaces has included the use of fluorinated surface modifying macromolecules (SMMs). These macromolecules have been reported to establish fluorinated functional groups at surfaces of polymeric materials without significantly affecting the physical properties of the base polymer. However, to date there has been relatively little information published on the nature of the surface structure for PES materials containing these SMMs. In this study, synthesized SMMs with varying chemical compositions were characterized and blended with PES, and fabricated into flat sheet membranes. The bulk thermal transitions of PES materials were not significantly altered by the addition of 4 wt% SMMs. Contact angle data showed that the addition of SMMs in PES created more hydrophobic surfaces, accompanied by an increase in surface heterogeneity. X-ray photoelectron spectroscopy studies confirmed the presence of elemental fluorine at the surface. Through microscopy studies, it was shown that surface modification was achieved by the migration of SMM concentrated microdomains to the air-membrane interface. The generated microdomains (approximately 1-2 microm in diameter) are dispersed within the top 8 microm of the surface. The concentration of microdomains was gradually depleted from the surface to the bulk of the membrane. A schematic of the morphology for SMMs within the PES membrane surface was proposed. PMID- 11211160 TI - Infectious agents in coronary lesions obtained by endatherectomy: pattern of distribution, coinfection, and clinical findings. AB - BACKGROUND: Cytomegalovirus (CMV), Chlamydia pneumoniae (C. pneumoniae), and Helicobacter pylori (H. pylori) have been implicated in atherosclerosis and restenosis after angioplasty. The patterns of distribution within coronary lesions and possible coinfections of these pathogens in the coronary vasculature had not previously been evaluated. DESIGN: A prospective, observational clinical study. METHODS: Large coronary specimens (9-105 mm long) were obtained by endatherectomy of 53 patients undergoing aortocoronary bypass surgery. Samples were taken from two different sites of every lesion, resulting in a total of 106 probes. Presence of each pathogen was determined by polymerase chain reaction, subsequent hybridization, and DNA sequencing. RESULTS: Cytomegalovirus and C. pneumoniae were detected in 30 and 32% of the samples, respectively; H. pylori was not detectable. The pathogens were not homogeneously distributed. A concurrent infection with both pathogens was observed in five of 106 (5%) lesions and five of 53 (9%) patients. Restenotic lesions were more often found in specimens in which cytomegalovirus was detected (five of 16 versus two of 37). Patients with C. pneumoniae-positive coronary lesions more commonly presented with unstable angina. CONCLUSIONS: Inhomogeneous infections with cytomegalovirus and C. pneumoniae of coronary atherosclerotic lesions are found to be prevalent when serial analysis is performed. Concurrent infection with both pathogens occurs coincidentally; however, possible clinical implications of this new observation and the pathogenic impact on atherosclerosis need further investigation. PMID- 11211161 TI - Sex differences in morphology of coronary artery plaque assessed by intravascular ultrasound. AB - BACKGROUND: Results of autopsy studies have suggested that there are sex differences in morphology of coronary-artery plaques, but these differences have yet to be adequately evaluated in vivo. DESIGN AND METHODS: We performed preintervention intravascular ultrasound (IVUS) measurements on coronary plaques in a consecutive series of 76 men and 30 women with unstable angina pectoris. Both the target lesion and an adjacent reference site were evaluated. Arterial, plaque, and luminal areas were measured by planimetry. Plaques were classified as either calcified or uncalcified, and relative density of plaque was quantitatively assessed by videodensitometry, using a linear gray scale normalized with respect to density of adventitia. RESULTS: Although women were older than men (mean age 55.0 +/- 10.9 versus 60.4 +/- 12.2 years, P = 0.02), their target lesions were less dense (74.6 +/- 23.4 versus 86.2 +/- 22.2% of adventitial density, P = 0.02) and less often found to be calcified (20.0 versus 38.2%, P = 0.05). Similarly, reference sites in female subjects were less dense (77.6 +/- 15.3 versus 97.1 +/- 19.4% of adventitial density, P = 0.01). There was no sex difference in the severity of coronary stenosis. CONCLUSIONS: Both qualitative and quantitative sex differences in in-vivo morphology of coronary plaques morphology were detected by IVUS measurement. Plaques in women appear less videodense and are less often calcified than are those in men. Future studies employing sequential IVUS examinations are needed in order to determine whether these morphologic differences relate to a delay in initiation of plaques, slower progression of plaques, or other sex-specific modulators of plaque composition. PMID- 11211162 TI - Diffusion of gamma globulin into the arterial wall identifies localized entry of lipid and cells in atherosclerosis. AB - BACKGROUND: The localization of atheromatous lesions in vulnerable arteries and their relatively rare occurrence in other arteries of the same subject cannot be explained by current theories of the aetiology of atherosclerosis. OBJECTIVE: To determine whether abnormal diffusion of gamma globulin into the arterial wall from the lumen will identify defects of barrier function allowing localized entry of lipid and cells in atherosclerosis. METHODS: Paraffin sections of left anterior descending coronary arteries and corresponding internal thoracic arteries from 80 human subjects aged 1-65 years were stained for gamma globulin by the immunoperoxidase technique. Duplicate sections were stained with orcein to demonstrate the elastin structure. RESULTS: The barrier function of the luminal surface of the thickened intima was associated with the presence of an elastin lamina beneath the endothelial cells. With advancing age, the coronary arteries exhibited breakdown of this barrier function in localized areas with entry into the arterial wall of gamma globulin, lipid and cells. This was rare in the internal thoracic artery. CONCLUSION: Lack of continuity or incomplete formation of this sub-endothelial lamina, which was seen particularly in the coronary artery, was associated with localized entry into the arterial wall of gamma globulin, lipid and cells from the circulating blood and with the development of atheromatous lesions. PMID- 11211163 TI - There is no effect on remodeling of vascular wall 4 weeks after local delivery of antithrombin in a porcine model of coronary overstretching. AB - BACKGROUND: Antithrombin III is an effective endogenous inhibitor of thrombin with antiproliferative and anti-inflammatory capabilities. Systematic administration of direct thrombin inhibitors as well as of antithrombin has proven effective at reducing formation of neointima after injury to vessel wall in various animal models. Local delivery of antithrombin attenuates deposition of platelets after balloon injury to porcine coronary vessels. OBJECTIVE: To test our hypothesis that local delivery of antithrombin affects remodeling of vessel wall after balloon injury to the left anterior descending artery (LAD) in pigs. METHODS: With a balloon:vessel diameter ratio of 1.5 deep vessel-wall injury was performed with conventional balloon angioplasty in the LAD in 16 pigs. After balloon injury the pigs were administered locally two doses of 2.5 ml antithrombin (250 U) or, as a control, two doses of 2.5 ml albumin (10 mg). All pigs were administered 200 U/kg bodyweight heparin before catheterization. The animals were then kept in stalls and fed normal grain. After approximately 4 weeks the animals were killed and lesions were assessed by computer-assisted image analysis. The areas of each vessel-wall layer and the percentage area stenosis were calculated. As a measure of injury, the length of rupture of the lamina elastica interna was measured. RESULTS: The injury was found to be equally profound in pigs of these groups. There was no significant difference between the groups concerning the areas of vessel-wall layers. The percentage area stenosis was similar for pigs in these two groups (36.5 +/- 14.9% for pigs in the antithrombin group versus 35.4 +/- 16.2% for pigs in the control group, NS). CONCLUSIONS: Local delivery of 250 U antithrombin to the LAD in pigs did not affect remodeling of the vessel wall 4 weeks after balloon injury. PMID- 11211164 TI - Acute exposure to a high cholesterol diet attenuates myocardial ischemia reperfusion injury in cholesteryl ester transfer protein mice. AB - BACKGROUND: Previous experiments have demonstrated that acute exposure to a high cholesterol diet (HCD) increases the severity of myocardial infarction in animals. Recent results suggest that the process is modulated by multiple genes and their interactions with circulating cholesterol. DESIGN: In the present study cholesteryl-ester-transfer-protein (CETP) transgenic mice were generated and fed a normal rodent-chow diet, HCD for 1 week, or a HCD for 6 weeks in order to define the role of CETP in myocardial infarction after acute exposure to a HCD. METHODS: Cholesterol levels in mice of all groups were measured. Separate groups of mice were exposed to 30 min of in-vivo occlusion of coronary artery and 2 h of reperfusion. We assessed the sizes of the ischemic zone and infarct using Evans blue and 2,3,5-triphenyltetrazolium chloride. RESULTS: The extent of infarction (percentage infarct/area at risk) was significantly less (P < 0.05) after 1 week of a HCD (18.7 +/- 7.0%) than those for the normal diet group (51.4 +/- 5.5%) and the group fed a HCD for 6 weeks (44.4 +/- 5.2%). Additionally, there was significantly less infiltration of neutrophils into the ischemic-reperfused mouse hearts for mice fed a HCD for 1 week. Levels of reduced and oxidized glutathione in the hearts of CETP mice were measured for separate groups of animals. The reduced:oxidized-glutathione ratio was significantly (P < 0.01) lower for mice fed a HCD for 1 week (1.5 +/- 0.1) than it was for mice fed a normal diet (3.6 +/ 0.3) and a HCD for 6 weeks (3.3 +/- 0.2). CONCLUSIONS: These data suggest that activity of CETP in hypercholesterolemic mice has an acute effect on size of infarct after 1 week of a HCD. This suggests that CETP induces tolerance of ischemia in the mice fed a HCD via mild oxidative stress. PMID- 11211165 TI - Serial evaluation of coronary flow reserve by transesophageal doppler echocardiography after angioplasty of proximal left anterior descending coronary artery: a 6-month follow-up study. AB - BACKGROUND: Coronary flow reserve can be estimated by transesophageal Doppler echocardiography (TDE). OBJECTIVE: To evaluate the coronary flow reserve by TDE, serially over 6 months' follow-up, after successful percutaneous transluminal coronary angioplasty (PTCA) of proximal left anterior descending coronary artery (LADA). METHODS AND RESULTS: We performed TDE examination of 30 patients (mean age 55 +/- 9 years) 72 h, 3 months, and 6 months after PTCA of LADA. Selective angiography of LADA was repeated 72 h and 6 months after PTCA of LADA. Velocity of flow in LADA was measured before and 2 min after cessation of intravenous infusion of dipyridamole (0.56 mg/kg in 4 min). The dipyridamole: rest mean diastolic velocity ratio was considered as an index of coronary flow reserve (CFR). For 20 of 21 patients with CFR > 2 there was no restenosis, whereas coronary angiography revealed restenosis in eight of nine patients with CFR < 2. The sensitivity was 88.9% and the specificity was 95.2%. For the 21 patients without restenosis mean CFR was 2.1 +/- 0.1 72 h after PTCA, had increased to 3.1 +/- 0.3 (P < 0.0001) 3 months after PTCA, and remained stable thereafter (3.0 +/- 0.9). CONCLUSION: CFR after PTCA of proximal LADA can be evaluated serially by transesophageal Doppler echocardiography. CFR of LADA in patients without restenosis is increased 3 months after PTCA and remains stable thereafter. PMID- 11211166 TI - Histopathologic validation of in-vivo angioscopic observation of coronary thrombus after angioplasty in a porcine model. AB - BACKGROUND: Coronary angioscopy has been reported to be superior to angiography and intravascular ultrasound for detecting intracoronary thrombus. However, in vivo histopathologic validation of angioscopic detection of intracoronary thrombus had not been performed. OBJECTIVE: To perform histopathologic validation of in-vivo angioscopic detection of coronary thrombus. DESIGN: An experimental, blinded comparison of angioscopy and histopathology. METHODS: Coronary angioscopy was performed from 0 to 14 days after angioplasty in 39 porcine coronary arteries. When thrombus was detected by angioscopy, it was subclassified into white, mixed red-white, or red thrombus according to color. By histopathology the presence of thrombus was determined and subclassified into platelet-rich, mixed platelet-erythrocyte, or erythrocyte-rich thrombus. RESULTS: Angioscopy correctly classified 19 of 21 coronary thrombi (sensitivity 90%) but incorrectly classified nine of 18 arteries without formation of thrombus as having a thrombus (specificity 50%). Positive and negative predictive values were 68 and 82%, respectively. The angioscopic subclassification of thrombus into white, mixed red white, or red thrombi was not correlated to the corresponding histopathologic morphology (platelet-rich, mixed platelet-erythrocyte, or erythrocyte-rich) of the observed thrombi (chi2 test: P = 0.5). CONCLUSIONS: Angioscopic detection of thrombus in vivo had high sensitivity and negative predictive value but low-to moderate specificity and positive predictive value. Visual assessment of color of angioscopically detected thrombi seemed not to reflect histopathologic morphology of thrombus according to the definitions used in the present study. PMID- 11211167 TI - Changes in the use of medications after acute myocardial infarction: possible impact on mortality after myocardial infarction and long-term outcome. AB - OBJECTIVE: To describe the change in the use of medication after acute myocardial infarction (AMI) and discuss its possible impact on risk and risk indicators for death. PATIENTS: All patients discharged alive after hospitalization for AMI at Sahlgrenska Hospital (covering half the community of Goteborg, i.e. 250,000 of 500,000 inhabitants) during 1986-1987 (period I) and at Sahlgrenska Hospital and Ostra Hospital (covering the whole community of Goteborg, 500,000 inhabitants) during 1990-1991 (period II). METHODS: Overall mortality was retrospectively evaluated during 5 years of follow-up. RESULTS: In all, 740 patients were included in the study during period I and 1448 during period II. The 5-year mortalities were 44.1% for period I patients and 39.3% for period II patients (P = 0.036). The relative risk of death for period II patients was 0.78 [95% confidence interval (CI) 0.67-0.89, P = 0.0005] after adjustment for differences at baseline. There was a significant interaction with a history of congestive heart failure; improvement in duration of survival was found only for patients without such a history. During period I, only 3% of patients were administered fibrinolytic agents, compared with 33% of patients during period II (P < 0.0001). During period I, aspirin was prescribed for 13% of patients discharged from hospital compared with 79% during period II. Other changes in treatment on going from period I to period II included increases in prescription of beta-blockers and angiotensin converting enzyme inhibitors. After adjustment for various risk indicators for death, relative risk of death for those administered fibrinolytic agents was 0.60 (95% CI 0.18-2.02) for patients in the period-I cohort and 0.68% (95% CI 0.51-0.91) for those in the period-II cohort. Adjusted relative risk of death for those prescribed aspirin upon discharge from hospital was 0.81 (95% CI 0.52-1.25) for period-I patients and 0.71 (95% CI 0.56-0.91) for period-II patients. The adjusted relative risk of death for those administered beta blockers was 0.72 (95% CI 0.55-0.96) for period-I patients and 0.70 (95% CI 0.55 0.90) for period-II patients. CONCLUSION: Increased use of fibrinolytic agents and aspirin for AMI as well as a moderate increase in use of beta-blockers and angiotensin converting enzyme inhibitors was associated with a parallel reduction in age-adjusted mortality during the 5 years after discharge from hospital. However, this improvement was seen only for patients without histories of congestive heart failure. PMID- 11211168 TI - Soluble adhesion molecules, endothelial function and vitamin E in type 1 diabetes. AB - BACKGROUND: Elevated levels of soluble adhesion molecules are found in subjects with vascular disease and inconsistently in subjects with conditions predisposing them to atherosclerosis, such as hypercholesterolaemia and diabetes. Oxidized low density lipoprotein (LDL), protein kinase C and lower than normal levels of NO appear to be important for expression of adhesion molecules, raising the possibility that vitamin E is useful for downregulating levels. We have recently shown that administration of 1000 IU vitamin E for 3 months will improve endothelial vasodilator function (EVF) in uncomplicated type-1 diabetes. OBJECTIVE: To determine whether levels of soluble adhesion molecules in young subjects with uncomplicated diabetes are elevated, whether there is a relationship between levels of soluble adhesion molecule and EVF as well as parameters of diabetes and lipid levels and whether an improvement in EVF related to vitamin E therapy is also associated with a decrease in levels of soluble adhesion molecules. DESIGN: A randomized, placebo-controlled, study. RESULTS: There was no difference between levels of soluble vascular cell adhesion molecule 1 (VCAM-1; 621 +/- 17 versus 635 +/- 37 ng/ml) and P-selectin (59 +/- 2 versus 57 +/- 6 ng/ml) for the diabetic and control groups. For the diabetic cohort, levels of soluble VCAM-1 were inversely related to flow-mediated vasodilatation of the brachial artery (r = -0.41, P < 0.005) and directly related to levels of total cholesterol (r = 0.44, P < 0.005) and LDL cholesterol (r = 0.42, P < 0.01) and duration of diabetes (r = 0.55, P < 0.0005) but there was no relationship with susceptibility of LDL to oxidation or vitamin-E content of LDL. Levels of soluble P-selectin were directly related to duration of diabetes (r = 0.43, P < 0.05) and inversely related to size of LDL particles (r = 0.32, P < 0.05) but were not related to EVF. Vitamin E produced no change in levels of soluble P-selectin and VCAM-1. CONCLUSIONS: Levels of soluble VCAM-1 and P-selectin in young subjects with type-1 diabetes and no evidence of overt vascular disease do not appear to be elevated and are not influenced by vitamin-E supplementation. PMID- 11211169 TI - Comparison of deposits of versican, biglycan and decorin in saphenous vein and internal thoracic, radial and coronary arteries: correlation to patency. AB - BACKGROUND: Matrix proteoglycans versican, biglycan and decorin are important determinants of vessel-wall structure and pathology. Thickened myxoid intimas typical of restenosis and early atherosclerosis are enriched in versican and biglycan, proteoglycans that promote proliferation and migration of smooth muscle cells and bind lipoproteins. In contrast, compact fibrous intimas are characterized by decorin. OBJECTIVE: To compare the distribution patterns of these matrix proteoglycans, and changes induced by organ culture in coronary artery, saphenous vein, internal thoracic artery (ITA), and radial artery, and correlate differences to patency. METHODS: Vessels were collected at the time of bypass surgery and heart transplantation and either fixed for immunohistochemistry or prepared for organ culture. Vessels in culture were labelled with [3H]-glucosamine and processed for autoradiography and immunohistochemistry. Distribution patterns for proteoglycans and radio-labelling were determined morphometrically. RESULTS: Distribution profiles in coronary artery and saphenous vein were similar, with relatively high levels of subendothelial versican and biglycan and low levels of decorin. In culture subendothelial incorporation of [3H]-glucosamine and immunostaining for versican and biglycan, but not decorin, were significantly increased. In contrast, the thin intima of the ITA was relatively enriched in decorin compared with the medial layers and in culture intimal staining for decorin increased markedly compared with a modest increase for biglycan and no change for versican. There was an even distribution in radial artery of all three proteoglycans across the intima without subendothelial accumulations. In culture there was an increase in staining intensity for proteoglycans of the radial artery. Neither the ITA nor radial artery exhibited an increase in subendothelial incorporation of [3H] glucosamine in culture. CONCLUSIONS: The distributions of proteoglycans, and responses to culture correlate to the known differences in patency between grafted saphenous vein and ITA and predict that the radial artery will outperform the saphenous vein but might not be as good as the ITA for long-term patency. PMID- 11211170 TI - Left anterior descending artery length in left and right coronary artery dominance. AB - BACKGROUND: Coronary stenosis of the left anterior descending artery (LAD) is respected by cardiologists because of its negative influence on morbidity and mortality. An important anatomical consideration is the length of the LAD. OBJECTIVE: To investigate the relationship between length of LAD and coronary dominance. DESIGN: Retrospective comparison of 100 consecutive angiograms with left coronary dominance with 100 consecutive angiograms with right coronary dominance. The relationship between the length of the LAD and coronary dominance was analyzed. METHODS: We retrospectively compared 100 consecutive angiograms with left coronary dominance (the posterior descending artery being supplied by the circumflex artery) with 100 consecutive angiograms with right coronary dominance (the posterior descending artery being supplied by the right coronary artery). LADs were categorized into three types: type A, LAD terminating before the cardiac apex; type B, LAD reaching the apex but not supplying the inferoapical segment of the left ventricle; and type C, LAD wrapping around the apex and supplying the inferoapical segment. LAD typing was also analyzed in relation to gender. RESULTS: It was found that the LAD wrapped around the apex in 87% of cases of left coronary dominance but only in 47% of patients with right coronary dominance, and that the long LADs were more frequently seen in women than in men, irrespective of coronary dominance. CONCLUSIONS: We found that the LAD in left coronary dominance is usually long and wraps around the apex, and believe that angiographic interventions in such cases have important clinical significance. PMID- 11211171 TI - Dickinson W. Richards, MD: through a grand-daughter's eyes. PMID- 11211172 TI - Bibliography. Current world literature. PMID- 11211173 TI - Mucosal damage and recovery of the intestine after prolonged preservation and transplantation in dogs. AB - BACKGROUND: Although much is known about the mucosal damage that occurs after intestinal warm ischemia and reperfusion and its recovery, little is known about the effect of cold preservation and transplantation on the mucosa. We studied the electrophysiological, biochemical, and histological changes of the intestinal mucosa after preservation for 24 hr and subsequent transplantation. METHODS: The small intestines from adult mongrel dogs were harvested. The intestines were orthotopically autotransplanted immediately (control group) or after preservation for 24 hr (preservation group). Jejunal and ileal tissues were taken before harvesting, at the end of preservation, 1 hr after reperfusion, and on postoperative days 3, 7, 14, and 28. The Ussing chamber method was used to study the electrophysiologic changes. Tissue maltase, diamine oxidase, and ornithine decarboxylase were measured. A histological analysis was also performed. RESULTS: Control group grafts showed no evident deterioration in electrophysiology, biochemistry, or morphology. In contrast, preservation group grafts exhibited electrophysiological and biochemical degradation, complete denudation of the villi, and crypt injury (especially in the ileum) after reperfusion. Electrophysiologic function and the mucosa biochemical marker recovered within 3 days in the jejunum and within 7-14 days in the ileum; however, histological recovery of mucosal injury required 28 days in the jejunum and more than 28 days in the ileum. CONCLUSIONS: Our study showed that despite severe destruction of mucosal integrity by prolonged preservation and transplantation, the intestinal mucosa has an enormous regenerative capacity. Our study also showed that regeneration was more pronounced in the jejunum than in the ileum. PMID- 11211174 TI - Effect of liver transplantation on islet allografts: up-regulation of Fas ligand and apoptosis of T lymphocytes are associated with islet graft tolerance. AB - BACKGROUND: Liver allografts in spontaneously tolerant strain combinations can protect other organs of the same donor origin from rejection and reverse ongoing rejection in previously placed grafts. The aims of this study were to examine whether liver allografts have the same protective effect on islet allografts and to investigate the underlying mechanisms. METHODS: PVG islets were transplanted beneath the kidney capsule of streptozotocin-induced diabetic DA rats with or without liver allografting. The cellular infiltrate, and the extent of apoptosis and of Fas ligand (FasL) expression in the islet grafts were evaluated on days 2, 4, and 7 after transplantation by means of immunostaining and the in situ terminal deoxynucleotide transferase-mediated dUTP nick end labeling assay. Donor and recipient mixed lymphocyte reactions (MLR) were determined at 7 days or 100 days after islet transplantation. RESULTS: Islet allografts transplanted alone were rapidly rejected within 5-8 days. Rejection was delayed, but not prevented, when islets were transplanted simultaneously with the liver. Liver transplantation 1 month before islet transplantation resulted in long-term survival (>100 days) of islet grafts in three of seven animals, whereas the other four died of liver rejection with functional islet grafts. Liver transplantation on day 4 after islet grafting reversed ongoing islet rejection and led to indefinite islet graft survival in three of seven cases. There was a progressive increase of cellular infiltration in all of the islet allografts, but the intensity of the infiltrate did not correlate with the outcome of the islet allografts. Islet rejection was characterized by an early dominance of monocytes/macrophages and CD25+ T cells in the infiltrates, a high incidence of apoptotic beta cells in grafts, and a sensitized status in the MLR. Tolerance of islet allografts was associated with increased numbers of dendritic cells in the graft infiltrates, up-regulation of FasL, and prominent apoptosis of alloreactive leukocytes in the islet grafts, as well as donor-specific MLR suppression in long term survivors. CONCLUSIONS: These results demonstrate that the extent of the protective effect of liver transplantation on islet allografts varies with the time of liver grafting, ranging from delay in islet rejection to complete islet acceptance. Islet graft tolerance induced by liver transplantation is the result of an immune process that involves up-regulation of Fas ligand expression on, and apoptosis of, islet graft infiltrating lymphocytes. PMID- 11211175 TI - A novel iron chelator in combination with a P-selectin antagonist prevents ischemia/reperfusion injury in a rat liver model. AB - BACKGROUND: Hepatic ischemia/reperfusion (I/R) injury is associated with early and late graft failure after liver transplantation. A major mechanism is leukocyte adhesion to endothelium followed by release of reactive oxygen intermediates. We examined whether desferriexochelin 772SM (D-Exo), a lipid soluble iron chelator that prevents hydroxyl radical formation, can enhance the capacity of recombinant P-selectin glycoprotein ligand immunoglobulin (rPSGL-Ig), a glycoprotein that binds to P-selectin and inhibits neutrophil adhesion, to protect against I/R injury in an ex vivo rat liver model. METHODS: Rat livers were harvested and stored for 6 hr at 4 degrees C in University of Wisconsin solution and then perfused with oxygenated whole blood for 2 hr. Three groups were studied (n=6 rats/group): an untreated control group; a group that received 0.4 mg/kg rPSGL-Ig intraportally at the time of harvest; and a group that received 0.4 mg/kg rPSGL-Ig plus 1 micromol D-Exo intraportally both at the time of harvest and at the onset of reperfusion. Liver portal venous blood flow was assessed during perfusion, and at the end of each experiment, liver samples were collected for blinded histological evaluation and biochemical analyses. RESULTS: Livers treated with D-Exo + rPSGL-Ig had significantly higher blood flow than livers treated with rPSGL-1Ig alone (P<0.05), and both treatment groups had higher blood flow than controls (P<0.001). Production of carbonyl proteins, a protein oxidation product, was significantly reduced in the D-Exo + rPSGL-1Ig group (P<0.02 vs. controls), but not in the rPSGL-Ig alone group. Total reduced glutathione was significantly higher than controls in the D-Exo + rPSGL-Ig group (P<0.001 vs. controls), but not in the rPSGL-Ig alone group, indicating less oxidative stress in the D-Exo-treated group. Production of malondialdehyde, an index of lipid peroxidation, was significantly less than controls in both treatment groups (P<0.03). Histopathological findings paralleled these results with Banffs scores of 3.3+/-0.5, 1.8+/-0.4, and 1.3+/-0.5 in the control, rPSGL Ig alone, and D-Exo plus rPSGL-Ig groups, resp. CONCLUSION: rPSGL-Ig provides partial protection against I/R injury to ex vivo rat livers; however, the addition of D-Exo substantially increases protection by reducing oxidative injury. These findings may have clinical relevance in preventing the consequences of I/R injury after liver transplantation. PMID- 11211176 TI - Apoptosis of superantigen-activated T cells induced by mycophenolate mofetil treatment. AB - BACKGROUND: Mycophenolate mofetil (MMF), an ester prodrug of mycophenolic acid (MPA), is a potent immunosuppressive agent used in clinical organ transplantation. MPA preferentially inhibits the type II isoform of inosine monophosphate dehydrogenase, depletes GTP, suppresses transfer of mannose and fucose to glycoproteins, and prevents lymphocyte proliferation in vivo. Whether MMF can also delete activated T cells in vivo by triggering an apoptotic signal was addressed in this study. To this end we analyzed the activity of MMF in mice injected with the bacterial superantigen staphylococcal enterotoxin B (SEB). Superantigens bind to MHC class II molecules without requirement for processing, and activate subsets of CD4+ and CD8+ T cells whose T cell receptor beta chains express Vbeta family-specific homologous sequences. This model that shares several features with direct allorecognition has the unique advantage of allowing a precise monitoring of activated T cells. METHODS: BALB/c mice treated with MMF (100 mg/kg/ day) or vehicle were injected with SEB. Serum cytokines, CD4+ and CD8+ Vbeta8+ cells were monitored in blood and lymphoid tissues, and apoptosis was determined by externalization of membrane phosphatidyl serine, double strand DNA breaks, and expression of B220 antigen by Vbeta8+ cells. RESULTS: MMF treatment decreased tumor necrosis factor alpha, interferon gamma, and interleukin-10 secretion induced by SEB. It did not modify other early activation events (blast transformation, CD69 and CD25 expression) but completely inhibited SEB-induced expansion of Vbeta8+ cells by inducing apoptosis of SEB-reactive T cells. A similar effect was observed in CD95-ligand-deficient mice. Repeated SEB injections associated with MMF resulted in a marked decrease of CD8+ Vbeta8+ T cells. SEB-induced increase of Vbeta8+ thymocytes was not prevented by MMF treatment. CONCLUSION: Results obtained in this in vivo model suggest that MMF treatment may induce deletion of activated peripheral T cells and decrease early cytokine responses. PMID- 11211177 TI - Endotoxin-mediated delayed islet graft function is associated with increased intra-islet cytokine production and islet cell apoptosis. AB - BACKGROUND: Primary nonfunction resulting in immediate graft loss is responsible for the failure of a large number of islet transplants. Evidence is accumulating to single out endotoxin contamination of the various reagents needed for islet isolation as a major cause of early graft loss. METHODS: Islets isolated with endotoxin-containing (400 endotoxin units/ml) collagenase type V and "endotoxin free" (3.1 endotoxin units/ml) Liberase were compared. Graft function was assessed using a syngeneic murine model of marginal islet mass transplantation. Pro-inflammatory cytokine production by islets was measured by ELISA in culture supernatants, and quantitative reverse transcriptase-PCR. Islet cell apoptosis was measured using the annexin assay. RESULTS: Graft function was significantly delayed when islets were isolated with endotoxin-containing collagenase. Addition of endotoxin to the Liberase solution similarly delayed graft function. After 18 hr in culture, collagenase-isolated islets released higher amounts of proinflammatory cytokines compared with Liberase-isolated islets (interleukin-6: 2,185+/-1,174 pg/ml vs. 520+/-201 pg/ml; tumor necrosis factor-alpha: 304+/-298 pg/ml vs. 0; IL-1beta: 12.5 pg/ml+/-12.5 vs. 0). This observation correlated with higher cytokine mRNA expression in collagenase-isolated islets. The percentage of apoptotic islet cells immediately after isolation was 17.2%+/-9.4 in collagenase isolated islets and 7.1%+/-2.1 in Liberase-isolated islets. CONCLUSIONS: We propose that endotoxin contamination is the primum movens of a chain of events that involves intra-islet cytokine production and release and islet cell apoptosis, and endotoxin contamination can ultimately lead to primary nonfunction in vivo. This emphasizes the fact that using endotoxin-free reagents during isolation is a key factor for successful islet transplantation. PMID- 11211178 TI - A human CD46 transgenic pig model system for the study of discordant xenotransplantation. AB - BACKGROUND: The chronic shortage in the supply of human organs available for allotransplantation has turned attention toward the use of animals as potential donors, with pigs as the most likely species under consideration. Hyperacute rejection, the initial and immediate barrier to a pig-to-primate xenograft, has been addressed by generation of transgenic pigs that express the human membrane bound complement-regulatory proteins CD59 and/or CD55. Difficulty has been encountered in generation of transgenic animals that express a third membrane bound complement-regulatory protein, CD46. METHODS: We have generated transgenic animals by using a large genomic construct that encompasses the entire human CD46 gene. RESULTS: We report the first description of transgenic mice and pigs that express high levels of human CD46 in a cell and tissue type-specific manner, resembling patterns of endogenous CD46 expression observed in human tissues. Furthermore, when human CD46 transgenic porcine hearts were transplanted into baboons, the grafts did not succumb to hyperacute rejection, and survival extended for up to 23 days. Under the same conditions, nontransgenic grafts underwent hyperacute rejection within 90 min. CONCLUSIONS: This is the first report to describe generation of transgenic pigs that express human CD46, and the first in vivo demonstration of the ability of human CD46 expressed on pig organs to regulate complement activation and overcome hyperacute rejection upon transplantation of a vascularized organ into nonhuman primates. PMID- 11211179 TI - Graft function and survival depend primarily on host factors in compromised recipient models of orthotopic liver transplantation in the rat. AB - BACKGROUND: Experimental models of liver transplantation use normal recipients, although most patients undergoing liver transplantation suffer from acute or chronic liver failure. This study was designed to analyze the outcome of orthotopic liver transplantation in compromised rat hosts. METHODS: Recipient animals were either rats with D-galactosamine-induced acute or rats with chronic liver failure secondary to common bile duct ligation. Liver damage was evaluated by monitoring enzymes, bilirubin, ammonia levels, prothrombin, thrombin time, and cytokines. In vivo function of hepatocytes and sinusoidal endothelial cells were evaluated by indocyanine green and hyaluronic acid uptake. Transplantation was performed in normal, acute, and chronic liver failure rats at different time points using either freshly harvested or cold-preserved syngeneic livers. RESULTS: Survival with fresh grafts decreased significantly when transplants were performed 48 hr after the induction of acute liver failure. No rats with acute liver failure survived transplantation with grafts stored for 12 or 24 hr although in chronic failure survival was more 80%. Survival of acute liver failure rats receiving 6 hr preserved grafts was 16.6% compared with 83.3% observed with fresh grafts transplanted at the same time point after D galactosamine injection. Elevated tumor necrosis factor-alpha and interleukin 1beta levels as well as impaired sinusoidal endothelial cell function were detected in acute liver failure rats with 6 h preserved grafts. CONCLUSION: These results suggest that preoperative status and different host factors have a significant effect on outcome and graft function after liver transplantation in rats. PMID- 11211180 TI - Distribution of upper limb skin cancers in relation to arteriovenous fistula side in renal transplant recipients. AB - BACKGROUND: Renal transplant patients have an increased incidence of skin cancers, predominantly on sun-exposed surfaces. Clinical observation identified some patients with an increased number of viral warts, keratoses, and skin malignancies on the side of the arteriovenous fistula. METHODS: In a population of 980 patients who underwent transplantation in Oxford, we identified 68 patients with known fistula site who had developed cutaneous malignancies on the upper limbs. We compared the distribution of skin malignancies in relation to the side of the arteriovenous fistula with regard to histologically confirmed Bowen's disease, squamous cell carcinoma, basal cell carcinoma, and keratoacanthoma. RESULTS: No significant difference was found between the distribution of skin cancers, total malignancies or subgroups, in the fistula limbs compared with the nonfistula limbs. CONCLUSION: We have been unable to demonstrate that the presence of an arteriovenous fistula predisposes to the development of cutaneous malignancies. PMID- 11211181 TI - Aspergillus antigenemia sandwich-enzyme immunoassay test as a serodiagnostic method for invasive aspergillosis in liver transplant recipients. AB - BACKGROUND: Invasive aspergillosis (IA) is an important cause of mortality in liver transplant patients. Clinical and microbiological diagnosis is difficult, and it is frequently achieved only after autopsy. Early diagnosis and antifungal therapy could improve the survival of these patients. METHODS: A retrospective case-control study of IA in liver transplant recipients (OLT) was performed to determine the value of the detection of galactomannan Aspergillus antigen in serum using a sandwich-ELISA test (Platelia, Sanofi Diagnostic Pasteur). Stored frozen serum specimens obtained during the posttransplantation period were used. RESULTS: Fourteen cases of IA were diagnosed in 240 OLT recipients (IA incidence: 5.8%) during 5 years with 13 deaths (mortality: 93%). Nine case patients and 33 control patients met the criteria required for being considered "valid" for antigenemia analysis. In five of the nine case patients, a serum sample was positive for Aspergillus antigenemia detection. The median value was 5.7 ng/ml (range: 1.6-6.6). Sensitivity of the test was 55.6%, specificity was 93.9%, the positive predictive value was 71.4%, and the negative predictive value was 88.6%. The likelihood ratio of a positive test was 9.2. CONCLUSIONS: Galactomannan detection in serum could be useful for an early diagnosis of IA in OLT recipients. PMID- 11211182 TI - Renal transplantation in a patient with end stage renal disease due to cholesterol embolism. AB - BACKGROUND: Renal failure due to cholesterol emboli is mostly irreversible. Therefore chronic renal replacement therapy is necessary. However, to the best of our knowledge no published experience exists with renal transplantation in patients with end-stage renal disease (ESRD) due to cholesterol embolization (CE). METHODS: Renal transplantation was performed in a 64-year-old man who suffered from ESRD due to CE after coronary angiography. Because our patient presented with a typical profile of cardiovascular risk factors effective long term control of these risk factors before and after transplantation was a mandatory prerequisite before considering transplantation. RESULTS: After one rejection episode serum creatinine values have been stable and no major complications have occurred during a follow-up of 18 months. No signs of recurrent cholesterol emboli into the donated kidney were seen in renal biopsies performed due to graft rejection. CONCLUSION: Cholesterol embolization is an uncommon reason for ESRD and mainly occurs after invasive vascular procedures in patients with hyperlipidemia, arterial hypertension, and smoking. Because ESRD due to CE often is irreversible, chronic renal replacement therapy may be necessary. As demonstrated in our report, renal transplantation should be considered. However, in this setting effective long-term control of the underlying risk factors before and after renal transplantation has to be ensured. PMID- 11211183 TI - Successful long-term kidney-pancreas transplants regardless of C-peptide status or race. AB - BACKGROUND: We have previously shown that our patient population of 60% minority races has end-stage renal disease primarily as a result of diabetes mellitus and hypertension. It therefore was logical to explore the restoration of normal insulin production and renal function by simultaneous pancreas-kidney (SPK) transplantation, without regard to race. This study represents new analyses integrating race with C-peptide status and reports the outcome of 136 SPK transplantations performed over the last 10 years. RESULTS: Of the 49 African Americans with diabetes mellitus and end-stage renal disease, 60% were type I and 40% were type II, based on C-peptide levels. In comparison, only 16% of Caucasians were type II. The average age at onset of diabetes mellitus was 15.7 years for type I compared with 20.7 years for type II (P>0.05). The actuarial 10 year survival rates for the 136 SPKs were 91.79% (patient), 85.07% (pancreas), and 83.58% (kidney). The type I and type II survival rates were similar in the two diabetic groups. CONCLUSIONS: The data strongly suggest that pretransplant C peptide status does not influence the outcome of SPK transplantation in patients with renal failure from diabetes mellitus. SPK transplants should be offered to all suitable diabetic patients with renal failure regardless of C-peptide status or race. PMID- 11211184 TI - The addition of mycophenolate mofetil for suppressing hepatitis B virus replication in liver recipients who developed lamivudine resistance--no beneficial effect. AB - BACKGROUND: Mycophenolate mofetil is used as an immunosuppressive agent in liver transplant recipients. Its active compound, mycophenolic acid, also inhibits the replication of Epstein-Barr virus and human immunodeficiency virus. Based on a study indicating the effectiveness of mycophenolate mofetil on hepatitis B virus (HBV) replication in infected human hepatocyte cells in culture, we examined the efficacy of mycophenolate mofetil in suppressing HBV replication in lamivudine resistant liver allograft recipients with recurrent HBV infection. METHOD: The study population included four liver allograft recipients (three males, one female), median age 51 years (range 41-57 years), with recurrent HBV infection who proved to be resistant to lamivudine. All received standard maintenance immunosuppression therapy. Median pretreatment serum alanine aminotransferase level was 75 mu/L (range 39-182 mu/L) and HBV DNA level (quantitative dot blot), 70 pg/ml (range: 10-5,000 pg/ml). Mycophenolate mofetil, 1.0 g p.o. twice daily, was administered for 8 weeks, concomitant with a reduction in the maintenance corticosteroid and cyclosporine doses. RESULTS: After mycophenolate mofetil was administered, the serum alanine aminotransferase level increased in two patients, did not change in one, and decreased in one. Serum HBV DNA levels increased in three patients and decreased (nonsignficantly) in only one patient. Two patients complained of abdominal pain and nausea. CONCLUSIONS: Mycophenolate mofetil at the dosage used is not effective in suppressing HBV replication after liver transplantation. PMID- 11211185 TI - Living-related liver transplantation for type II citrullinemia using a graft from heterozygote donor. AB - BACKGROUND: Type II citrullinemia (CTLN2) characterized by a liver-specific argininosuccinate synthetase deficiency is an adult onset genetical disorder caused by the mutation of SLC25A13 gene, which results in fulminant hyperammonemia often with poor prognosis. METHODS: A 16-year-old Japanese boy presented fulminant hyperammonemia and encephalopathy and recovered after aggressive medical treatment. The patient was diagnosed as CTLN2 by plasma amino acid pattern and detection of the mutated SLC25A13 gene. We performed living related liver transplantation (LRLT) using a graft from the genetically proven heterozygote father. RESULTS: Serum amino acid concentration was normalized within a day after transplantation without protein restriction and medication. The patient's postoperative course was natural. The patient is back in school 6 months after surgery. CONCLUSIONS: Living-related liver transplantation using a graft from genetically proven heterozygote donors might be a permissible treatment modality for CTLN2. Long-term observation may be necessary to make a definite conclusion possible. PMID- 11211186 TI - Pharmacokinetics and tolerability of 40-0-[2-hydroxyethyl]rapamycin in de novo liver transplant recipients. AB - BACKGROUND: 40-0-[2-Hydroxyethyl]rapamycin (RAD), a novel macrolide with potent immunosuppressive and antiproliferative activities, prevents rejection in animal allotransplantation models. This phase I trial assessed the effects of bile diversion, administration route, and time after transplant on RAD pharmacokinetics after single-dose administration in de novo liver allograft recipients. The influence of RAD on cyclosporine (CsA) pharmacokinetics and the safety of RAD were also evaluated. METHODS: Twenty-six de novo liver allograft recipients were assigned to one of four treatment groups based on the presence or absence of a T tube, administration route (nasogastric or nasoduodenal), and timing of RAD administration. Patients received a single 7.5-mg RAD dose on one to three occasions in addition to CsA (Neoral) and corticosteroids. Steady-state cyclosporine profiles with and without RAD coadministration were evaluated. Results. Recipients with bile diversion demonstrated lower peak concentration (Cmax) than those without, but overall drug exposure (AUC) was not altered. Cmax and AUC were not influenced by administration route. A trend towards higher Cmax on postoperative day 3 than on postoperative day 1 was noted, although AUC was not altered. Single-dose RAD coadministration did not affect steady-state CsA pharmacokinetics. RAD was well tolerated and caused few drug-related adverse effects. RAD administration did not increase infection rates or produce clinically significant changes in laboratory parameters. Conclusions. In de novo liver transplant recipients, the overall extent of RAD absorption was not influenced by bile diversion, administration route, or time of administration. CsA pharmacokinetics were not affected by single-dose RAD coadministration. RAD capsules administered in single doses of 7.5 mg were well tolerated and safe. PMID- 11211187 TI - Incidence of renal artery stenosis in pediatric en bloc and adult single kidney transplants. AB - BACKGROUND: The incidence, time of onset, and outcome of transplant renal artery stenosis (TRAS) in pediatric en bloc (PT) and adult single-kidney (AT) transplants were reviewed. METHODS: Forty-three cases (7 PT and 36 AT) of suspected TRAS were selected out of 367 functioning grafts (35 of them PT). Diagnosis was performed by digital subtraction arteriography. Percutaneous transluminal angioplasty (PTA) was performed when needed. RESULTS: Seven (20%) PT and 24 (7.1%) AT presented TRAS. Time of onset was 7+/-1 months in PT and 18+/-17 months in AT (P<0.05). PTA was performed in all cases of TRAS in PT and in 19 AT. One PT and 7 AT had re-stenosis. There was no significant difference in renal function after treatment. Control of blood pressure improved in both groups. CONCLUSIONS: Recipients of PT grafts showed a higher incidence and earlier onset of TRAS. Re-stenosis was more frequent in AT. PMID- 11211188 TI - Human papillomavirus infection and anogenital condyloma in bone marrow transplant recipients. AB - BACKGROUND: Secondary malignant diseases are late complications after allogeneic bone marrow transplantation (BMT). Anogenital lesions associated with human papillomavirus (HPV) infection have been described in renal transplant recipients but not after BMT. HPV types 16 and 18 are strongly linked to the malignant transformation. METHODS: In a series of 238 patients with allogeneic BMT, three had anogenital lesions. We looked for HPV in DNA extracted from embedded tissue to study HPV genotypes, p53 expression, and ploidy. RESULTS: In two patients, HPV sequences were detected. One of them, with giant condyloma, had HPV type 18 and two aneuploid clones, but p53 expression was not found. CONCLUSION: As in solid organ transplant recipients, anogenital condyloma may develop after BMT. Because the oncoprotein of HPV is able to bind and to degrade p53, it may lead to genetic instability, and subsequently to malignant transformation. PMID- 11211189 TI - Inhibition of herpes simplex virus type 1 by the experimental immunosuppressive agent leflunomide. AB - BACKGROUND: Despite advances in antiviral chemotherapy, herpes simplex virus type 1 (HSV-1), continues to complicate the clinical course of many allograft recipients. We have previously demonstrated that the experimental immunosuppressive agent leflunomide inhibits production of cytomegalovirus by interference with virion assembly. We test the hypothesis that this agent exerts similar antiviral activity against HSV-1. METHODS AND RESULTS: Plaque assay of virus yield from endothelial or Vero cells after inoculation with each of four clinical HSV-1 isolates demonstrated a dose-dependent reduction of virus production in the presence of pharmacologic concentrations of A77 1726, the active metabolite of leflunomide. DNA dot blot and biochemical assay of viral DNA polymerase activity indicated that A77 does not inhibit viral DNA synthesis. Rather, as visualized by transmission electron microscopic method, this agent seems to disrupt virion assembly by preventing nucleocapsid tegumentation. CONCLUSIONS: These findings, in demonstrating that leflunomide exerts antiviral activity against HSV-1 by mechanisms similar to those we have previously shown with cytomegalovirus, imply that this agent may possess broad spectrum activity against other herpesviruses. PMID- 11211190 TI - Bovine islets are less susceptible than human islets to damage by human cytokines. AB - BACKGROUND: The potential benefits of islet xenografting in type 1 diabetes include the intriguing, but still unanswered, possibility that the grafted xenoislets may be less subjected to human autoimmune attack. Cytokines may play a major role in the pathogenesis of autoimmune diabetes by causing impairment of insulin release and pancreatic islet cell toxicity. METHODS: We compared insulin secretion, islet cell death and survival, inducible nitric oxide synthase (iNOS) mRNA expression, nitrite production, and Bcl-2 and Bax mRNA expression in isolated human and large mammal (bovine) islets exposed to 50 U/ml recombinant human interleukin-1, 1,000 U/ml recombinant human tumor necrosis factor-alpha and 1,000 U/ml recombinant human interferon-gamma. RESULTS: After 24-hr exposure, a marked decrease of glucose-stimulated insulin secretion was observed with human, but not with bovine islets. After 48-hr exposure, human, but not bovine, pancreatic islets showed a significantly higher percentage of apoptotic cells compared to controls. Treatment of human islets with human cytokines induced up regulation of iNOS mRNA, increased levels of nitrites, and down-regulation of Bcl 2 mRNA, with unchanged levels of Bax mRNA. These parameters were not affected by cytokines in bovine islets. CONCLUSIONS: Bovine islets are less susceptible than human islets to the effects of human cytokines, which may be a potential advantage of xenotransplantation. PMID- 11211191 TI - Coronary artery endothelial dysfunction after ischemia-reperfusion and acute untreated rejection in a canine heterotopic heart transplantation model. AB - BACKGROUND: Acute rejection is a common problem in heart transplantation and may contribute to the development of cardiac allograft vasculopathy. This study was designed to evaluate the mechanisms of coronary endothelial dysfunction associated with ischemia-reperfusion and acute untreated rejection. METHODS: Two groups of mongrel dogs (n=7 per group) underwent heterotopic cervical heart transplantation without immunosuppression. Allografts were harvested on posttransplant day 1 (group 1) and day 5 (group 2). A third group of unoperated dogs served as control (group 3). After harvesting, epicardial coronary arteries were studied in organ chamber for endothelium-dependent and independent reactivity. RESULTS: Group 1 displayed multifocal ischemic damage without any rejection while hearts from group 2 reached grade IV rejection. Immunohistochemical studies for von Willebrand factor showed expression on coronary endothelial cells in all animals with scattered areas of denudation in transplanted groups. Endothelium-dependent responses to acetylcholine, calcium ionophore A23147, and bradykinin were unaffected in groups 1 and 2. Endothelial relaxations to sodium fluoride (Gi-protein activator) was significantly reduced in group 1 and significantly increased in group 2 compared with control. Responses to serotonin and UK14304 (receptors linked to Gi-protein) were significantly increased in group 2. Responses to thrombin were decreased in both groups. Endothelium-independent responses were unaffected. CONCLUSIONS: In the canine model of heterotopic heart transplantation, the early (24 hr) endothelial dysfunction seen after transplantation is specific to the thrombin receptor and the Gi-protein signaling pathway. Acute untreated rejection did not modify the alteration in endothelial reactivity to thrombin but enhanced the sensibility of the Gi-protein signaling pathways. PMID- 11211192 TI - Induction of antigraft and antirecipient antibody responses after fully allogeneic and semiallogeneic rat small bowel transplantation. AB - BACKGROUND: Given the potential influence of alloantibodies on organ graft outcome, this study investigated the induction of antigraft and antirecipient antibodies after allogeneic and semiallogeneic rat small bowel transplantation. METHODS: Fully allogeneic, unidirectional rejection and unidirectional graft versus-host disease (GvHD) heterotopic small bowel transplantation was performed using DA, PVG, and (PVGxDA)F1 donor-recipient combinations. Serum was obtained before and at time points after transplantation and incubated with blood from untransplanted DA and PVG rats. Antibody binding to T cells was detected by whole blood flow cytometry using FITC-conjugated anti-rat IgM murine monoclonal antibody. Antibody levels were determined by reference to a standard curve of fluorescent intensity generated using a serum sample with known anti-target cell IgM activity. Data are presented as arbitrary units/ml (AU/ml). RESULTS: In the PVG-->DA combination, five of six DA recipients had detectable anti-graft (PVG) antibodies by day 4 after transplantation (mean 72 AU/ml) and all animals were positive by day 6 (976 AU/ml). Antirecipient (DA) antibodies were also induced, however, they were only apparent after 6 days in five of eight animals (90 AU/ml). Antigraft (DA) antibody responses were also induced in the DA-->PVG combination (day 6-218 AU/ml), however no antirecipient (PVG) response was apparent. Transplantation induced antirecipient (DA) antibodies in the unidirectional GvHD model (day 6-90 AU/ml) and an anti-graft (PVG) response in the unidirectional rejection model (day 6-60 AU/ml). However, the latter was quantitatively lower than that generated in the PVG-->DA combination (day 6-976 AU/ml). CONCLUSIONS: Antigraft and antirecipient antibody responses are simultaneously induced after fully allogeneic small bowel transplantation, despite rejection being the predominant clinical feature. Further studies are required to elucidate their influence on graft outcome. PMID- 11211193 TI - Accumulating monocytes in the vasculature of rat renal allografts: phenotype, cytokine, inducible no synthase, and tissue factor mRNA expression. AB - BACKGROUND: Necrotic patches and hemorrhagic lesions develop in the renal tissue between day 4 and day 5 after transplantation of fully allogeneic DA rat kidneys to LEW recipients. These lesions are at least in part due to destruction and obstruction of blood vessels. Damage of graft endothelial cells and blood coagulation are likely to be mediated by intravascular graft leukocytes. However, this cell population has not been thoroughly characterized before. METHODS: We perfused untreated control kidneys, renal isografts, and allografts on day 4 after transplantation with phosphate-buffered saline/ethylenediaminetetraacetic acid to harvest leukocytes from both the blood stream as well as from the marginal intravascular pool. The mRNA expression of typical products of activated monocytes was analyzed in reverse-transcriptase polymerase chain reaction experiments. Graft monocytes were purified and their immunophenotype was investigated by flow cytometry. RESULTS: Allograft rejection led to a 10-fold increase in the number of intravascular graft leukocytes compared to isografts. A mean number of about 100x10(6) leukocytes was harvested from a single allogeneic kidney, about 73% of these cells were monocytes and most of them displayed an activated phenotype. Compared to isografts, intravascular allograft leukocytes displayed an increased expression of tumor necrosis factor-alpha, inducible NO synthase and tissue factor. CONCLUSIONS: Our study shows that large numbers of activated monocytes accumulate inside allograft vessels. As they express genes the products of which might damage the allograft by inducing cell death or thrombosis, we speculate that they directly participate in allograft destruction. PMID- 11211194 TI - Successful outcome with a "quintuple approach" of posttransplant lymphoproliferative disorder. AB - BACKGROUND: The treatment of posttransplant lymphoproliferative disorder (PTLD) remains empirical. We review our treatment of seven cases of PTLD consisting of five interventions: 1) reduction of immunosuppression; 2) antiviral drugs; 3) interferon-alpha; 4) gamma-globulins; and 5) anti-CD19 monoclonal antibodies. METHODS AND RESULTS; Seven consecutive patients who had undergone a simultaneous pancreas-kidney, liver, heart, or kidney transplantation were treated. One patient acquired a primary EBV infection with an oligoclonal immunoblastic lymphoma early after pancreas-kidney transplantation; all others developed a monoclonal polymorphic or immunoblastic lymphoma 2 to 123 months after transplantation. In all patients extranodal sites were involved, in three the graft was also involved. Five patients received the full quintuple approach and all rapidly obtained a complete remission (CR) with a median follow-up of 31 months (7-74 months). Of the two patients who did not receive interferon-alpha for fear of graft rejection one responded slowly with a CR after 7 months, and the other obtained a rapid CR followed by a relapse at 4 months. All three patients with a liver or heart transplant could keep their graft. All patients are still alive with a median follow-up of 31 months (7-74 months). CONCLUSION: This combined approach resulted in a favorable outcome in patients with high risk monoclonal PTLD after solid organ transplantation. PMID- 11211195 TI - A randomized and prospective study comparing treatment with high-dose intravenous immunoglobulin with monoclonal antibodies for rescue of kidney grafts with steroid-resistant rejection. AB - BACKGROUND: The aim of this study was to compare the effectiveness of intravenous immunoglobulin (IVIg) versus monoclonal anti-CD3 as a treatment for steroid resistant rejections. From January 1995 to June 1997, 30 patients were analyzed. They were randomized into two groups. Resistant rejections were diagnosed by core biopsy. Group A received 500 mg/ kg/day IVIg (Sandoglobulin) for 7 consecutive days, whereas group B received 5 mg/day of OKT3 for 14 consecutive days. Daily T cell CD3+ peripheral count was performed for 14 days for group B. The immunosuppression was similar for both groups. Cyclosporine was stopped during both treatments. METHODS: Demographic factors, HLA mismatch, creatinine levels before and after treatment, and the incidence of rejections after treatment (up to 1 month) were taken into account for this study. RESULTS: Data from different samples were compared using Fisher's exact test. Graft and patient survival were analyzed using the Kaplan-Meier method. The were no significant differences found in age, graft origin, HLA mismatch, or time of follow-up until the episode of rejection. Success was achieved for 11 (73.3%) of 15 of group A and 13 (86.6%) of 15 of group B (P=0.79). Creatinine levels before and after treatment were as follows: A, 2.99+/-1.30 mg/dl and 2.1+/-0.70 mg/dl versus B, 3.1+/-1.1 mg/dl and 2.5+/-0.8 mg/dl. Besides, we did not observe differences in the creatinine 1 month after treatment (A: 2.35+/-0.78 mg/dl; B: 2.51+/-1.10 mg/dl; P=0.66) nor in the third month (A: 1.83+/-0.58 mg/dl; B: 2.30+/-0.89 mg/dl; P=0.24). The incidence of rejections after treatment was 5 (46%) of 11 for group A and 9 (75%) of 12 for group B (P=0.4). The patient survival rates 2 years after treatment were 87 and 92% for A and B groups, respectively. Graft survival was identical (80% in both groups). CONCLUSION: Should the favorable result presented in this report be confirmed in larger number of patients, IVIg could become the preferable choice of rejection treatment for steroid-resistant rejection because of a complete absence of the unwanted side effects commonly associated with OKT3. PMID- 11211196 TI - Nosocomial outbreak of parvovirus B19 infection in a renal transplant unit. AB - BACKGROUND: Parvovirus B19 (B19) infection is known to cause chronic infection leading to anemia in immunocompromised patients. Although nosocomial B19 infections in immunocompetent patients have been documented, no outbreaks in immunocompromised patients have been previously reported. Whether transmission can occur from a patient with chronic infection is also unknown. METHODS: An outbreak of B19 infection in a renal transplant unit was investigated by molecular analysis of the virus strains and a case-control study. RESULTS: Three patients had genetically identical virus strains suggesting the occurrence of nosocomial transmission. The index case transmitted infection many weeks after the onset of her clinical symptoms. Other patients at risk of acquiring infection were those most intensively immunosuppressed. Viral load in the serum correlated with the hematological response. A rebound in the viral load was associated with clinical relapse and the failure of i.v. immunoglobulin therapy. CONCLUSION: Nosocomial transmission of B19 can occur from immunocompromised patients even when they are in the chronic stage of the infection. The clinical and virological response to i.v. immunoglobulin therapy is variable and depends on the overall level of immunosuppression of the patient. PMID- 11211197 TI - Occult nonhematopoietic malignancies present at autopsy in solid organ transplant patients who died within 100 days. AB - BACKGROUND: Patients are at an increased risk for developing malignancies after transplantation. Lymphomas, skin malignancies, Kaposi's sarcomas, and cervical/vulvar neoplasms are the most common, but visceral malignancies are also well documented, with a reported frequency ranging from 1% to 6%. These visceral tumors represent a mix of neoplasms that were clinically occult at the time of transplantation and those that arise de novo after transplantation. Little information, however, is available on the frequency of clinically occult malignancies at the time of transplantation and their contribution to the number of posttransplant malignancies. METHODS: A retrospective study was performed of all patients who received an organ transplant from January 1981 to June 1997 and died within 100 days, a time interval in which epithelial malignancies found at autopsy were presumed to have been present, but clinically occult, at the time of transplantation. RESULTS: A total of 375 patients were studied who received the following organ transplants: 231 liver, 52 heart, 26 heart and lung, 32 lung, and 34 kidney. Eleven malignancies were identified for an overall frequency of 2.9% and included three thyroid carcinomas, three carcinoids of the small bowel, two lung carcinomas, one laryngeal carcinoma, one renal cell carcinoma, and one seminoma. CONCLUSION: The 2.9% frequency of malignancies seen in this study suggests that a small, but significant, number of patients have occult malignancies at the time of transplantation and that these occult tumors contribute substantially to the number of malignancies that present clinically after transplantation. PMID- 11211199 TI - The use of pretransplant erythropoietin to normalize hemoglobin levels has no deleterious effects on renal transplantation outcome. AB - BACKGROUND: The aim of this study was to establish the outcome of renal transplantation in patients given pretransplant erythropoietin (EPO) treatment targeted at reaching a normal hemoglobin concentration (Hb), compared to those given EPO-treatment aimed at maintaining subnormal Hb. METHODS: A total of 416 patients from Scandinavian countries and with renal anaemia were enrolled to examine the effects of increasing Hb from a subnormal level (90-120 g/liter) to a normal level (135-160 g/liter) by EPO treatment. Half of the patients were randomized to have their Hb increased, with the other half randomized to maintain a subnormal Hb. Thirty-two patients from the normal Hb group and 24 patients from the subnormal group received a renal graft during the study period. The outcomes of these transplantations were examined prospectively for 6 months. RESULTS: Preoperative Hb levels were 143+/-17 and 121+/-14 g/liter in the two groups, respectively (P<0.0001). The Hb remained higher in the normal Hb group during the first 2 weeks after transplantation. The percentage of patients requiring postoperative blood transfusions in the normal Hb group was 16%, compared with 50% in the subnormal group (P<0.01). No statistically significant difference in the proportion of functioning grafts or in the serum creatinine levels could be detected. No correlation between EPO treatment and creatinine levels after transplantation was found. The frequency of adverse events was similar in the two groups. CONCLUSIONS: EPO treatment aimed at reaching a normal Hb in renal transplant recipients reduces the postoperative requirement for blood transfusions and has no deleterious effects on kidney graft function. PMID- 11211198 TI - Safety, tolerability, and efficacy of cyclosporine microemulsion in heart transplant recipients: a randomized, multicenter, double-blind comparison with the oil-based formulation of cyclosporine--results at 24 months after transplantation. AB - BACKGROUND: The widespread use of cyclosporine has improved the survival of cardiac transplant patients as a result of reduced morbidity and mortality from rejection and infection. The original oil-based form of cyclosporine demonstrated unpredictable absorption resulting in an increased frequency of acute and chronic rejection in patients with poor bioavailability. The primary end. points of the present, prospective, randomized multicenter, double-blind trial were to compare the efficacy of the micro-emulsion form of cycolsporine (CsA-NL) with the oil based formulation as determined by cardiac allograft and recipient survival and the incidence and severity of the acute rejection episodes and to determine the safety and tolerability of CsA-NL compared with Sandimmune CsA-(SM) in the study population. The 6-month analysis of the study showed reduced number of CsA-NL patients requiring antilymphocyte antibody therapy for rejection, fewer International Society of Heart and Lung Transplantation grade > or =3A rejections in female patients and fewer infections. Our report represents the final analysis of the results 24 months after transplantation. METHODS: A total of 380 patients undergoing de novo cardiac transplants at 24 centers in the United States, Canada, and Europe were enrolled in this double-blind, randomized trial evaluating the efficacy and safety of CsA-NL versus CsA-SM. Acute allograft rejection was diagnosed by endomyocardial biopsy and graded according to the International Society of Heart and Lung Transplantation nomenclature. Kaplan Meier analysis and Fisher's exact test were used for comparisons between groups. RESULTS: After 24 months, allograft and recipient survival were identical in both groups. There were fewer CsA-NL patients (6.9%) requiring antilymphocyte antibody therapy for rejection than in the CsA-SM-treated patient group (17.7%, P=0.002). There were fewer discontinuations of study drug for treatment failures in the CsA NL groups (7; 3.7%) compared with the CsA-SM group (18; 9.4%, P=0.037). The average corticosteroid dose was lower in the CsA-NL group (0.37 mg/kg/day) compared with the CsA-SM group (0.48 mg/kg/day, P=0.034) over the 24-month study period. Overall, there was no difference in blood pressure or creatinine between the two study groups. CONCLUSIONS: The final results of this multi-center, randomized study of two forms of cyclosporine confirmed that there were fewer episodes of rejection requiring antilymphocyte antibodies and fewer study discontinuations for treatment failures in CsA-NL-treated patients compared to those treated with CsA-SM. The use of CsA-NL did not predispose these patients to a higher risk of adverse events. PMID- 11211200 TI - Reinnervation of syngeneic pancreatico-duodenal grafts in rats. AB - BACKGROUND: Knowledge on the reinnervation of transplanted organs is scarce, and the aim of the study was therefore to evaluate to what degree syngeneic pancreas grafts were reinnervated in rats. METHODS: Syngeneic pancreatico-duodenal transplantations were performed in normoglycemic Wistar-Furth rats. Native and transplanted pancreas and duodenum were removed 4 or 40 weeks after implantation, and processed for indirect immunofluorescence using antibodies directed against vasoactive intestinal peptide, substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), tyrosine hydroxylase (TH), or the general neuronal marker protein gene product 9.5. RESULTS: Four weeks after transplantation a moderate to rich number of protein gene product 9.5-positive nerve fibers were found homogeneously distributed through the pancreas, probably representing the intrapancreatic nervous system, because the grafted pancreas lacked both a sympathetic (TH/NPY) and sensory (SP/CGRP) innervation 4 weeks after implantation. In a few of the animals there was a marked increase in SP immunoreactive nerves (lacking CGRP), most conspicuous in the duodenal portion, both 4 and 40 weeks after transplantation probably secondary to a chronic pancreatitis. The fibers seemed to emanate from intrapancreatic ganglia and possibly also from enteric neurons in adjacent parts of the duodenum. A few scattered vasoactive intestinal peptide-containing nerve fibers probably also emanating from local ganglia could be seen throughout the grafted pancreas both 4 and 40 weeks after transplantation. At 40 weeks after transplantation sympathetic (TH- and NPY-positive) nerve fibers were regularly seen, whereas CGRP-positive nerve fibers were still virtually lacking in the pancreas. To trace the origin of the ingrowing nerve fibers, the tracer True Blue was injected into the grafted pancreas of some rats 38 weeks after transplantation, i.e., 2 weeks before killing. True Blue-labeled nerve cell bodies were numerous in the celiac ganglion (presumably sympathetic nerves) and few in dorsal root ganglia (sensory nerves). CONCLUSIONS: The data suggest that the transplanted rat pancreas becomes reinnervated by mainly sympathetic nerve fibers. PMID- 11211201 TI - The impact of simultaneous pancreas-kidney transplantation on long-term patient survival. AB - BACKGROUND: Simultaneous pancreas-kidney transplantation (SPK) ameliorates the progression of microvascular diabetic complications but the procedure is associated with excess initial morbidity and an uncertain effect on patient survival when compared with solitary cadaveric or living donor renal transplantation. We evaluated mortality risks associated with SPK, solitary renal transplantation, and dialysis treatment in a national cohort of type 1 diabetics with end-stage nephropathy. METHODS: A total of 13,467 adult-type 1 diabetics enrolled on the renal and renal-pancreas transplant waiting list between 10/01/88 and 06/30/97 were followed until 06/30/98. Time-dependent mortality risks and life expectancy were calculated according to the treatment received subsequent to wait-list registration: SPK; cadaveric kidney only (CAD); living donor kidney only (LKD) transplantation; and dialysis [wait-listed, maintenance dialysis treatment (WLD)]. RESULTS: Adjusted 10-year patient survival was 67% for SPK vs. 65% for LKD recipients (P=0.19) and 46% for CAD recipients (P<0.001). The excess initial mortality normally associated with renal transplantation and the risk of early infectious death was 2-fold higher in SPK recipients. The time to achieve equal proportion of survivors as the WLD patients was 170, 95, and 72 days for SPK, CAD, and LKD recipients, respectively (P<0.001). However, the adjusted 5 year morality risk (RR) using WLD as the reference and the expected remaining life years were 0.40, 0.45, and 0.75 and 23.4, 20.9, and 12.6 years for SPK, LKD, and CAD, respectively. There was no survival benefit in SPK recipients > or =50 years old (RR=1.38, P=0.81). CONCLUSIONS: Among patients with type 1 DM with end stage nephropathy, SPK transplantation before the age of 50 years was associated with long-term improvement in survival compared to solitary cadaveric renal transplantation or dialysis. PMID- 11211202 TI - Retransplantation of the liver in children. AB - BACKGROUND: Because of the poor outcome of hepatic retransplantation, it is still debated whether this procedure should be performed in an era of donor organ scarcity. The aim of this study was to analyze outcome of hepatic retransplantation in children, to identify risk factors influencing this outcome, and to assess morbidity and causes of death. METHODS: A series of 97 children after a single transplantation and 34 children with one retransplantation was analyzed. RESULTS: The 1-, 3-, and 5-year survival of children with a retransplantation was 70, 63, and 52%, respectively, compared with 85, 82, and 78%, respectively, for children after a single transplantation (P=0.009). Survival of children with a retransplantation within 1 month after primary transplantation was worse (P=0.007) and survival of children with a late retransplantation was comparable (P=0.66) with single transplantation. In early retransplantations, the Child-Pugh score was higher, donors were older and weighed more, and more technical variant liver grafts were used compared with single transplantations. Biliary atresia and a high Child-Pugh score were associated with decreased patient survival after retransplantation. Sepsis was the most important complication and cause of death after retransplantation. CONCLUSIONS: Retransplantation is a significant event after pediatric liver transplantation. Outcome after hepatic retransplantation in children is inferior compared with single transplantation. This difference is explained by low survival after early retransplantation and can be explained by the poor clinical condition of the children at time of retransplantation, especially in children with biliary atresia, and by the predominant use of technical variant liver grafts in retransplantations. PMID- 11211203 TI - Comparison of famciclovir and lamivudine in the long-term treatment of hepatitis B infection after liver transplantation. AB - BACKGROUND: Preliminary results of short-term famciclovir and lamivudine therapy in patients with hepatitis B virus (HBV) infection after liver transplantation revealed promising results. In a retrospective study the efficacy of long-term treatment with these substances was compared. METHODS: A total of 53 HBV-infected adults (48 reinfections and 7 de novo infections) received antiviral treatment. A total of 32 of these patients were treated with famciclovir 3x500 mg, 20 of them were later switched to lamivudine. Fourteen patients received lamivudine, 150 mg/day orally, as first line therapy and 7 patients after failure of famciclovir prophylaxis. Follow-up time was 8 to 62 months (mean 35 months). Response to therapy (HBV-DNA negative) was compared using Kaplan-Meier estimates. Potential influence factors (HBV-DNA and HBeAg pretransplant, HDV coinfection, pretreatment with famciclovir and immunosuppression) on treatment response were analyzed by log. Rank test (univariate); then a multivariate analysis (Cox multiple stepwise regression model) was applied. RESULTS: A total of 19 and 76% of the patients treated with famciclovir and lamivudine resp. became HBV-DNA negative; 0 and 24% HBsAg negative. Lamivudine was also effective as second line therapy. In a multivariate analysis of all 73 treatment courses, lamivudine treatment and HDV coinfection were significant factors for better treatment response; regarding only the lamivudine group, negative HBeAg pretransplant was significant. Viral breakthrough after prolonged treatment occurred in 55% (lamivudine) to 80% (famciclovir) of treatment courses but was only accompanied by mild hepatitis. CONCLUSIONS: Lamivudine and famciclovir are potent drugs for the treatment of HBV infection after liver transplantation. The antiviral capacity of lamivudine is superior even after pretreatment with famciclovir but after prolonged treatment viral breakthrough is often observed. PMID- 11211204 TI - Liver transplantation for fulminant hepatic failure. PMID- 11211205 TI - Real-time display of the stomach slow wave and its parameters in a newly designed electrogastrographic system. AB - We designed a new three-channel electrogastrographic (EGG) system, which was easily operated on the Windows 95 platform and could automatically provide slow wave parameters. The purpose of the present study was to test its reliability and accuracy in clinical recording. The system included a signal acquisition device assembled on a printed circuit board. Recorded myoelectrical signals were filtered, amplified, digitized, and transmitted via this device into a notebook personal computer (PC). Based on the short-term Fourier transform the software could transfer the time domain of the signal into the frequency domain. Real-time displayed slow wave parameters, including dominant frequency/power, percent of normal frequency (2-4 cpm), instability coefficient in frequency/power, and power ratio, were automatically renewed every 64s. Twenty healthy subjects (M/F, 12/8; age, 23-51 years) were enrolled to measure both fast and postprandial myoelectrical activities for each 30-min recording. Our results indicated that meal ingestion significantly increased dominant frequency (3.15+/-0.20 vs 3.23+/ 0.23 cpm; P < 0.05) and power (26.1+/-3.8 vs 28.4+/-3.9 dB; P < 0.05). The power ratio of the meal effect was 2.02+/-2.07. Other parameters, including instability coefficient and percent of normal frequency, remained similar despite food ingestion. This newly designed EGG system is acceptable for clinically measuring gastric myoelectrical activity; the real-time display of many EGG parameters is an advantage with this new system. PMID- 11211206 TI - Distribution and molecular forms of adrenomedullin and proadrenomedullin N terminal 20 peptide in the porcine gastrointestinal tract. AB - Adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) are potent hypotensive peptides that are generated from the same precursor and expressed in a variety of mammalian tissues. The purpose of this study was to elucidate the distribution and endogenous molecular forms of AM and PAMP. To this end, we used new radioimmunoassays that recognize the ring structure of AM and the C-terminal region of PAMP to compare the distribution of AM and PAMP in porcine gastrointestinal tissues. Immunoreactive AM was abundant in the duodenum (0.334+/ 0.132 fmol/mg) and ileum (0.439+/-0.235 fmol/mg), and ubiquitous in other gastrointestinal tissues. The duodenal and ileal concentrations of AM were about 4 to 14 times higher than those in other gastrointestinal tissues. Similarly, immunoreactive PAMP was abundant in the duodenum (0.577+/-0.417 fmol/mg) and ileum (1.575+/-1.445 fmol/mg) and ubiquitous in other gastrointestinal tissues. The concentrations of immunoreactive AM and PAMP were highest in the ileum. Characterization of these peptides in the ileum, using high-performance liquid chromatography, showed that they were authentic. Furthermore, the concentrations of immunoreactive AM and PAMP in the mucosa and submucosa of the ileum were significantly higher than those in whole ileum. These results suggest that AM and PAMP play physiological roles in the porcine small intestine. PMID- 11211208 TI - High sensitivity of a novel ELISA for anti-M2 in primary biliary cirrhosis. AB - The use of an ELISA for the detection of anti-M2, a specific autoantibody in primary biliary cirrhosis (PBC), has been common in Japan. However, there are some problems in the sensitivity of this ELISA, especially in PBC patients showing antimitochondrial antibody (AMA)-negative sera or low AMA titers by immunofluorescence. Recently, a new ELISA for anti-M2 was developed, using porcine heart mitochondrial protein as the antigen. We report here comparative studies of the new and the former anti-M2 ELISAs. Porcine heart mitochondrial protein was prepared and used as the antigen for the new ELISA for anti-M2. Sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of this protein showed three major M2 antigen proteins. As the second antibody, peroxidase-conjugated anti-human mouse monoclonal IgM, in addition to monoclonal IgG, was included. The sera of 171 PBC patients were examined. As controls, we examined the sera of 167 non-PBC patients and the sera of 115 normal controls. The cut-off index was set at 10 U/ml, based on the results for the normal controls. No sera from the non-PBC patients or the normal controls were positive for anti-M2 by either the new or the former ELISA. However, the positivity rate for anti-M2 in PBC patients with the new ELISA was 78%; in contrast, that with the former ELISA was only 54%; this difference was significant (P = 0.00001). In particular, in 65 patients showing AMA titers of 1:20 or less, the positivity rate with the new ELISA was 51%; in contrast, that with the former ELISA was only 17%. As the sensitivity of the new ELISA is significantly higher than that of the former ELISA, especially for sera from patients showing AMA-negativity or low titers of AMA, the new ELISA is considered to be more effective than the former ELISA for use in anti-M2 screening assays in patients with PBC. PMID- 11211207 TI - Expression patterns of cell cycle-related proteins in a rat cirrhotic model induced by CCl4 or thioacetamide. AB - To analyze the aberrant expression of cell cycle-related proteins and their biological significance in relation to cirrhosis, we compared the cirrhotic patterns induced by two different types of cirrhotic agents, CCl4 and thioacetamide (TAA) in rats. CCl4 or TAA treatment was given to rats for 8 or 30 weeks, respectively, and the livers were removed at 9, 20, and 30 weeks after the experiment began. The TAA-induced fibrotic pattern was different from the CCl4 induced one, in terms of the formation of fibrous connective tissue and the proliferation of bile ductule cells. Cholangiofibrosis and clear cell foci were also observed in TAA-treated rats at 30 weeks. Histological examination revealed severe cirrhotic changes at 9 weeks in CCl4-treated rats and at 30 weeks in TAA treated rats. Immunoblotting for cyclin D1, E, A, B, and proliferating cell nuclear antigen (PCNA) and their counterpart protein kinases (CDK2, 4, and CDC2) showed significant overexpression in rats with severely cirrhotic livers. The p53 tumor suppressor protein increased dramatically in the CCl4-treated group, while it was not detected in the livers of TAA-treated rats. Upregulation of p21WAF1, a CDK inhibitory protein, was detected in TAA-treated rats, but not in CCl4-treated rats. Immunohistochemical data for cyclin D1, E, and PCNA were well correlated with immunoblotting data; these proteins were increased in hepatocytes surrounding the cirrhotic lesions, suggesting that hepatocyte regeneration is correlated with cell cycle-related protein expression in cirrhotic liver. In the TAA-treated rats, the expression of these proteins was increased both in hepatocytes and in ductule cells. Our data suggest that liver cirrhosis induced by CCl4 or TAA is associated with alterations in cell cycle-related proteins, and that the expression of these proteins is responsible for hepatocyte regeneration in the damaged liver and may be involved in liver carcinogenesis. PMID- 11211209 TI - Jejunal carcinoid tumor mimicking leiomyosarcoma: preoperative diagnosis by endoscopic biopsy. AB - Primary carcinoid tumor of the jejunum is rare, and is an unusual cause of massive gastrointestinal bleeding. A case of primary jejunal carcinoid tumor in a 39-year-old woman who presented with massive hematochezia is described. Both upper and lower gastrointestinal endoscopies showed no abnormalities. An abdominal computed tomographic scan, small-bowel barium contrast studies, and small-bowel endoscopy showed a subserosal mass, of 5 x 4 cm, with a cavity suggesting central necrosis, and a deep mucosal ulceration, located in the proximal jejunum. Although these clinical presentations were strongly suggestive of a leiomyosarcoma, histologic examination of biopsy samples obtained by enteroscopy confirmed the diagnosis of jejunal carcinoid tumor. The patient underwent radical jejunal resection and recovered uneventfully. In spite of the large size of the tumor, there was one solitary lymph node metastasis, but no evidence of liver metastases. This kind of jejunal carcinoid tumor, presenting with massive gastrointestinal bleeding and a subserosal bulky growth mimicking a leiomyosarcoma, has not been reported previously. Moreover, this is a rare case of a jejunal carcinoid which was diagnosed preoperatively by small bowel endoscopic biopsy. PMID- 11211210 TI - Nonrotation of the midgut with appendiceal mucocele in an adult. AB - Nonrotation of the midgut in adults and appendiceal mucocele are both rare pathological conditions. We report here the first case of nonrotation of the midgut associated with appendiceal mucocele. The patient was a 51-year-old man admitted to hospital with ileus. An upper gastrointestinal series and a barium enema revealed nonrotation of the midgut without midgut volvulus and with a mass in the ileocecal area. Laparotomy revealed an appendiceal mucocele adhering to the urinary bladder and the rectum. The mucocele had partly ruptured; yellowish mucinous material had entered the abdominal cavity, resulting in pseudomyxoma peritonei. Histological examination revealed a mucinous tumor of the appendix with borderline malignancy. In this patient, the ileus was caused by the appendiceal mucocele rather than being caused by nonrotation of the midgut. PMID- 11211211 TI - Superficial depressed early carcinoma that developed into protuberant advanced carcinoma in the transverse colon. AB - A screening colonoscopic examination in a 70-year-old man revealed a nonpolypoid type superficial depressed early carcinoma, about 2cm in diameter, in the transverse colon. The lesion was not resected and was observed because of coexisting nonresectable hepatocellular carcinoma (HCC). Fifteen months later, follow-up examinations revealed a polypoid type protuberant advanced carcinoma, about 6 cm in diameter, at the same site. Because complete response of the HCC had been induced by transarterial embolization, the colon carcinoma was operatively resected. There is an indefinite concept that colorectal carcinomas develop without substantial morphological changes, and no superficial depressed carcinoma that developed into a protuberant type advanced carcinoma has been reported. The case reported here provides evidence that some polypoid carcinomas arise from superficial depressed precursors. There is some intermingling between the two postulated colorectal carcinogenic pathways, the conventional polypoid pathway named the "adenoma-carcinoma sequence", and the nonpolypoid pathway, including so-called "de-novo" carcinogenesis. PMID- 11211212 TI - Antibacterial action of tryptanthrin and kaempferol, isolated from the indigo plant (Polygonum tinctorium Lour.), against Helicobacter pylori-infected Mongolian gerbils. AB - We evaluated the effect of tryptanthrin and kaempferol, both isolated from Polygonum tinctorium Lour., against Helicobacter pylori colony formation in vitro and in H. pylori-infected Mongolian gerbils. H. pylori suspension was mixed with solution of tryptanthrin and/or kaempferol and placed onto agar plates. These plates were incubated at 37 degrees C, under 10% CO2 for 5 days, and the H. pylori colonies were counted. For the in vivo experiment, Mongolian gerbils were inoculated with H. pylori ATCC 43504 orally. After 4 weeks, the infected gerbils were given tryptanthrin and/or kaempferol, administered orally, twice a day for 10 days. The animals were killed and the number of live H. pylori in their stomachs was determined. In vitro both tryptanthrin and kaempferol significantly decreased the numbers of H. pylori colonies a dose-dependent manner. An additive effect on colony formation was observed with the combined use. In the in vivo experiment, oral administration of tryptanthrin and/or kaempferol significantly decreased the numbers of colonies in the gerbils' stomachs. We concluded that tryptanthrin and kaempferol were effective against H. pylori in vivo. PMID- 11211213 TI - Hepatic adenomas treated with percutaneous ethanol injection in a patient with glycogen storage disease type Ia. AB - We report a 20-year-old man with glycogen storage disease type Ia (GSD Ia) who presented multiple hepatocellular adenomas (HCAs) in 1993 and in whom percutaneous ethanol injection (PEI) was conducted as treatment for some enlarging tumors beneath the liver surface. In a 6-year follow-up period, we observed gradual enlargement of some of the HCAs, and the rapid growth of a newly developed tumor. In August 1996, one slow-growth HCA was 52 mm in diameter and was located beneath the surface of the liver. We conducted PEI therapy to prevent its spontaneous rupture. During the following year, another tumor developed beneath the liver surface, but showed extremely rapid growth, reaching 51 mm in diameter, from being undetectable, within 12 months. PEI therapy was again conducted for this newly developed tumor. Although additional PEI therapy was required for each tumor, because of suspected recurrence, no findings of discrete recurrence have been detected by computed tomography and magnetic resonance imaging for more than 2 years, up to the time of this study. We consider PEI to be a useful and effective therapeutic modality for individual HCAs in patients with GSD Ia. PMID- 11211214 TI - What is the role of adrenomedullin and proadrenomedullin N-terminal 20 peptide produced in the gastrointestinal tract? PMID- 11211215 TI - Hepatocellular adenoma in type Ia glycogen storage disease. PMID- 11211216 TI - High amoxycillin resistance in Helicobacter pylori isolated from gastritis and peptic ulcer patients in western Nigeria. PMID- 11211217 TI - Cashing in your chips: speculation on the future of diagnostic laboratories in the era of DNA chips. PMID- 11211218 TI - Type III secretion systems and pathogenicity islands. AB - Some bacterial pathogens have evolved by acquiring pathogenicity islands (PIs), which are clusters of genes encoding virulence traits. PIs encoding the secretion of effector molecules via type III secretion (TTS) systems have been discovered in several gram-negative pathogens. TTS systems are involved in contact-dependent secretion of virulence factors and can facilitate delivery of toxins directly into target cells. The expanding list of bacteria found to contain clusters of TTS genes includes members of the genera Yersinia, Salmonella, Shigella, Escherichia, Pseudomonas, Bordetella, Burkholderia, Chlamydia and a number of plant pathogens or symbionts. This review discusses the current knowledge of the role of TTS PIs in pathogenicity, the genetic organisation and evolution of such systems,and the potential for using TTS systems as targets for novel treatments. PMID- 11211219 TI - Antibody isotypes to a Paracoccidioides brasiliensis somatic antigen in sub-acute and chronic form paracoccidioidomycosis. AB - This report describes the differences in isotype antibody reactivity against a crude Paracoccidioides brasiliensis antigenic preparation in the sub-acute (SAF) and chronic (CF) forms of paracoccidioidomycosis before treatment. IgG antibodies were detected in all patients, with a slightly but not significantly higher reactivity in the SAF. IgG1 antibodies were present, frequently at high levels, in both forms, whereas IgG3 was always low or absent. IgG2 antibodies were detectable in most patients, but at high levels in only a few CF patients. IgG4 was found mainly in SAF patients, whereas IgA was detected almost only in CF patients, probably due to a Th2 pattern of immune response in the more severe SAF, and the characteristic mucosal involvement of the CF, respectively. Immunoblot analysis showed that, in addition to the 43-kDa immunodominant fraction, other less well-characterised fractions were also recognised differentially by the isotypes and deserve further investigation. PMID- 11211220 TI - Verocytotoxin-producing Escherichia coli (VTEC) O157 and other VTEC from human infections in England and Wales: 1995-1998. AB - A total of 3429 isolations of verocytotoxin-producing Escherichia coli O157 (VTEC O157) was confirmed from human sources in England and Wales during the period 1995-1998. The largest annual total was 1087 in 1997. Most infections occurred in the third quarter of each year. The overall rate of infection ranged from 1.28 to 2.10/100,000 population and showed regional variation. The highest incidence was in children aged 1-4 years. Annually, between 5% and 11% of strains were from patients who had travelled abroad. There were 67 general outbreaks of infection represented by 407 (11.9%) VTEC O157 isolates. Outbreaks involved transmission by contaminated food or water, person-to-person spread and direct or indirect animal contact, and five were associated with foreign travel. The majority (76%) of strains carried verocytotoxin (VT) 2 genes and 23.3% were VT1+VT2. Most strains had the flagellar antigen H7, but c. 14% were non-motile. Approximately 20% of isolates were resistant to antimicrobial agents, predominantly streptomycin, sulphonamides and tetracycline. In addition to VTEC O157, strains of serogroup O157 that did not possess VT genes were identified. These were either derivatives of VTEC O157 that had lost VT genes or were strains with H antigens other than H7 that have never been associated with VT production. Strains of VTEC other than O157 were characterised. Most were associated with diarrhoea, bloody diarrhoea or haemolytic uraemic syndrome and had virulence markers in addition to VT. PMID- 11211221 TI - Multiple outbreaks of Norwalk-like virus gastro-enteritis associated with a Mediterranean-style restaurant. AB - The role of diverse infectious agents, particularly Norwalk-like viruses (NLV), in three successive gastro-enteritis outbreaks in one setting (a restaurant) was evaluated. Methods included standard bacteriological tests, specific tests for Escherichia coli, tests for verocytotoxins, electron microscopy (EM) for viruses and reverse transcription-PCR (RT-PCR) methodology for NLV. No pathogenic bacteria were detected. Verocytotoxin genes, although detected by PCR in the first outbreak, could not be confirmed in the E. coli isolated, so they did not appear to be of significance. NLV was the main agent detected in each of the three outbreaks. DNA sequencing and phylogenetic analysis of the amplified products obtained from the RT-PCR positive specimens indicated that only one NLV strain was involved in each outbreak, but the NLV strains responsible for the three outbreaks were different from each other. PCR technology for detection of NLV proved highly sensitive, but failed to detect one specimen which was positive by EM. The restaurant associated with the outbreaks is a Mediterranean-style restaurant where food from a common platter is typically eaten with fingers. The findings indicate that NLV was introduced by guests or staff and was not due to a long-term reservoir within the setting. PMID- 11211222 TI - Effect of short-chain carbohydrates on human intestinal bifidobacteria and Escherichia coli in vitro. AB - Plate counts and small subunit (SSU) rRNA abundance were used to study the effects of fructo-oligosaccharides (FOS), fructose, or galacto-oligosaccharides (GOS) on bifidobacterial populations in human faecal microbiotas. The bacteria were grown in pH-controlled anaerobic fermentation vessels. Untreated cultures and fructose-amended fermenters were used as controls. Bifidobacterium longum, B. adolescentis and B. angulatum comprised the dominant bifidobacterial populations throughout the experiment. No major differences were found in the four treatments, in terms of viable counts of the organisms or of total populations of bifidobacteria at any time point. However, large differences were observed with respect to the abundance of bifidobacterial SSU rRNA between the treatments. Greatest bifidobacterial SSU rRNA abundance was seen in FOS cultures, with the lowest in the untreated control fermentation. GOS and fructose also increased bifidobacterial SSU rRNA. Cultures supplemented with FOS and GOS were also associated with lower colony counts and SSU rRNA abundance for Escherichia coli, compared with fructose-supplemented and control fermenters. At the 24-h time point, the untreated control contained 19.8 microg of enterobacterial SSU rRNA/ml of culture fluid, compared with 11.4 microg/ml for the fructose fermentation, and 2.6 and 0.5 microg/ml for the FOS and GOS culture vessels, respectively. PMID- 11211223 TI - Antagonism against Vibrio cholerae by diffusible substances produced by bacterial components of the human faecal microbiota. AB - Cholera vibrios sometimes survive, probably in low-level silent populations, in the small intestine of chronic carriers or pass through the gastrointestinal tract of a few individuals without causing diarrhoea or colonisation. To understand these situations, the present study used plate cultures (ex-vivo test) to investigate the frequency of appearance of an inhibitory halo against Vibrio cholerae produced by faecal specimens from 92 healthy volunteers (40 females, 52 males) aged 4-61 years. The frequency of inhibitory halo was 20.6% in the whole group. An apparently higher percentage (27.3%) was observed in the age range 20 40 years when compared with the range 4-19 years (10.7%), but not the range 41-61 years (20.0%). Frequency was significantly higher in males (30.8%) than females (7.5%). The dominant microbiota of a volunteer whose faeces produced an inhibitory halo was isolated by plate culture of decimal dilutions in an anaerobic chamber. Potential isolates of 26 apparently different morphologies were associated with germ-free NIH mice. One week later, the inhibitory test showed an antagonistic halo around the faeces from the associated animals, but not from the axenic mice. Of the 26 bacteria isolated, two (Lactobacillus sp. and Peptostreptococcus sp.) produced a compound antagonistic against V. cholerae in an in-vitro assay. When bi-associated with germ-free mice those strains eliminated the vibrio from the intestinal ecosystem in c. 5 days. PMID- 11211224 TI - Investigation of the simian polyomavirus SV40 as a potential causative agent of human neurological disorders in AIDS patients. AB - Neurological diseases and a variety of neoplasms frequently occur in AIDS patients. Human JC and BK polyomaviruses have been associated with neurological disorders in such patients. SV40 polyomavirus sequences have been detected in human brain tumours, other neoplasms and normal tissues. JCV, BKV and SV40 DNA sequences were investigated in cerebrospinal fluid (CSF) samples from 12 AIDS patients affected by different neurological disorders, by PCR assay and filter hybridisation with specific internal oligoprobes, and DNA sequencing. Three of the 12 CSF samples were positive for JCV (one sample) or SV40 (one) DNA, or both (one). No sample was positive for BKV DNA. JCV- and SV40-specific genomic regions were confirmed by DNA sequencing. CSF samples from the two patients diagnosed clinically as having progressive multifocal leukoencephalopathy (PML) contained either JCV (one sample) or SV40 (one) DNA. The CSF found to contain both JCV and SV40 DNA originated from a patient with a cerebral mass lesion of unknown aetiology. These results suggest that SV40 may be involved in the aetiology of PML in AIDS patients, and raise the possibility that SV40 and JCV may act synergically in vivo to enhance their pathogenicity. PMID- 11211225 TI - Emergence of a high-level cefotaxime-resistant Streptococcus pneumoniae strain in New Zealand. AB - An increase in the number of cefotaxime-resistant pneumococci referred for surveillance to a central laboratory in New Zealand occurred in 1997-1998. The MIC of cefotaxime for 113 of 216 cefotaxime-resistant isolates of Streptococcus pneumoniae referred was > or = 4 mg/L. Most of the 113 isolates exhibited the same antibiotic resistance pattern and belonged to serotype 19F. To investigate the genetic relatedness of the isolates, 48 serotype 19F pneumococci with varying susceptibility to cefotaxime were further typed by macro-restriction analysis by use of pulsed-field gel electrophoresis. These results suggested that a multiresistant 19F strain of S. pneumoniae with high-level cefotaxime resistance had emerged from a pre-existing serotype 19F strain. PMID- 11211226 TI - PCR primers that can detect low levels of Mycobacterium leprae DNA. AB - There are several specific PCR-based methods to detect Mycobacterium leprae DNA, but the amplicons are quite large. For example, primers that target the 36-kDa antigen gene and are in common diagnostic use yield a 530-bp product. This may be a disadvantage when examining samples in which the DNA is likely to be damaged and fragmented. Therefore, two sets of M. leprae-specific nested primers were designed, based on existing primer pairs which have been shown to be specific for M. leprae. Primers that targeted the 18-kDa antigen gene gave an outer product of 136 bp and inner product of 110 bp. The primers based on the RLEP repetitive sequence yielded a 129-bp outer product and 99-bp nested product. With dilutions of a standard M. leprae killed whole-cell preparation as the source of DNA, both single-stage and nested PCR were performed after optimisation of the experimental conditions. Compared with the 36-kDa antigen gene primers, the 18-kDa antigen gene outer primers were 100-fold more sensitive and the RLEP outer primers were 1000-fold more sensitive. As an illustration of two possible applications of these new primers, positive results were obtained from three skin slit samples from treated lepromatous leprosy patients and three archaeological samples from human remains showing typical leprosy palaeopathology. It was concluded that these new primers are a useful means of detecting M. leprae DNA which is damaged or present at a very low level. PMID- 11211227 TI - Role of heparan sulphate proteoglycans as potential receptors for non-piliated Pseudomonas aeruginosa adherence to non-polarised airway epithelial cells. AB - Tight junctions seal polarised surface epithelial respiratory cells so as to prevent the passage of bacteria and toxins through the epithelial sheet. Disruption of tight junctions, which may occur during injury and repair processes of airway epithelium, favours potential bacterial interaction with receptors from cell basolateral membranes. Earlier studies reported that non-polarised and untight epithelial respiratory cells are highly susceptible to Pseudomonas aeruginosa adherence and internalisation. As heparan sulphate proteoglycans (HSP) from cell basolateral membranes in epithelial cells without tight junctions may become accessible to bacterial ligands, the present study investigated their role as potential receptors for non-piliate P. aeruginosa ligands. Treatment of cells with heparitinase I and II significantly reduced (51.2% and 51.7%, respectively) P. aeruginosa adherence to epithelial respiratory cells without tight junctions. The internalisation of bacteria was not affected by treatment with heparitinases. Treatment of the bacteria with heparin and heparan sulphate also significantly reduced their adherence to respiratory cells (34.3% and 43.7%, respectively). Treatment of cells with other enzymes (trypsin, lipase and chondroitinase ABC) or treatment of bacteria with chondroitin-4-sulphate did not modify the adherence to respiratory cells significantly. Both affinity chromatography and Western blotting assays showed the interaction of different P. aeruginosa outer-membrane proteins (OMPs) with heparin. Several bacterial strains showed differences in their profile of heparin-binding OMPs, but all exhibited low mol. wt (< 30 kDa) reactive proteins. Reactivity of whole bacterial cells with heparin was also observed by transmission electron microscopy. These results suggest that HSP are potential receptors for P. aeruginosa adherence to non-polarised and untight epithelial respiratory cells. PMID- 11211228 TI - Expression of type 1 fimbriae (SEF 21) of Salmonella enterica serotype enteritidis in the early colonisation of the rat intestine. AB - The involvement of type 1 fimbriae in colonisation of the rat gastrointestinal tract in vivo was investigated with Salmonella enterica serotype Enteritidis LA5 and a mutant of LA5 denoted EAV3 unable to elaborate type 1 fimbriae (SEF 21). Rats were given a single dose of LA5 or EAV3 or a 1:1 mixture of both. LA5 was found in higher numbers in the stomach and small intestine than EAV3 at 6 h after infection with a single strain, but not after 6 days. LA5 did not out-compete EAV3 when the strains were administered together. Indeed, after 6 and 21 days, EAV3 was found in the distal small intestine and large intestine in far higher numbers than LA5. These findings suggest that SEF 21 have an important role(s) in the early stages of infection in vivo. However, SEF 21 expression may disadvantage the pathogen in the longer term as indicated by EAV3 out-competing LA5 in the gut at 21 days. PMID- 11211229 TI - Pulmonary colonisation with Pneumocystis carinii in an immunosuppressed HIV negative patient: detection and typing of the fungus by PCR. AB - Mostly Pneumocystis carinii isolates from patients with acute pneumocystosis (PCP) have been typed until now. This report describes the typing of P. carinii organisms obtained from an HIV-negative patient without PCP. The patient underwent a broncho-alveolar lavage (BAL) to investigate an abnormal chest X-ray. He was diagnosed with sarcoidosis. However, a low level of P. carinii organisms undetectable by microscopy was detected in BAL fluid by two subsequent nested PCR assays: one assay amplifying a portion of the mitochondrial large subunit RNA gene and a second one amplifying the internal transcribed spacers (ITS) 1 and ITS 2 of the nuclear rRNA operon. This low level of the fungus did not reflect acute PCP. Indeed, the clinical outcome was improvement despite the absence of specific treatment. The patient was considered to be only colonised by the fungus. Analysis of sequences of ITS PCR products led to identification of genotype Gg. This information constitutes the first data concerning P. carinii ITS genotype from a patient without acute PCP and HIV. This type has been described previously in AIDS patients diagnosed with PCP. These results show that PCR and ITS genotyping could represent efficient tools for the further investigation of the role played by HIV-negative patients with pulmonary colonisation in the human reservoir of P. carinii. PMID- 11211230 TI - Enterohaemorrhagic Escherichia coli O157:H7: a red herring? PMID- 11211231 TI - Detection of adenovirus and rotavirus antigens by an immuno-gold lateral flow test and ultrasound-enhanced latex agglutination assay. PMID- 11211232 TI - Diurnal changes of tyrosine, dopamine, and dopamine metabolites content in the retina of rats maintained at different lighting conditions. AB - The aim of the study was to investigate the daily rhythms of tyrosine (Tyr), dopamine (DA), 3,4-dioxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) content in the retina of rats maintained under different lighting conditions. Studied substances were measured by highly sensitive high-performance liquid chromatography (HPLC) with an electrochemical detection method. It was found that the levels of Tyr, DA, DOPAC, and HVA change diurnally in the retina of adult Wistar rats maintained under standard cyclic lighting (12-h light/12-h dark). The maximum was found during the light phase of 12:12 light:dark photoperiod. Diurnal changes of DA, DOPAC, and HVA persisted in constant darkness. When the rats were maintained in constant lighting conditions for 2 d (light intensity, 200 lx), the rhythms of tyrosine, DA, and DOPAC completely disappeared. However the level of HVA was higher during the subjective day. The presence of diurnal rhythm of melatonin content in the retina of rats was confirmed by HPLC with an amperometric detection method. Since the presence of time cues is not necessary for manifestation of diurnal changes of DA and its metabolite content, it was concluded that the circadian oscillator drives these rhythms. Probably DA can serve as a zeitgeber for retinal circadian rhythms. PMID- 11211233 TI - Corticosteroids regulate the gene expression of FGF-1 and FGF-2 in cultured rat astrocytes. AB - The present data show that the gene expression of FGF-1 and FGF-2 is regulated by corticosteroids in rat type 1 astrocytes. In particular, the gene expression of FGF-1 is modulated by corticosteroids acting both on type I (minerocorticoid) and type II (glucocorticoid) receptors. In fact, at short times of exposure (2 h) a slight decrease in FGF-1 mRNA levels is induced by deoxycorticosterone, a steroid able to interact with the type I receptors; a similar effect is observed at 6 h following exposure to corticosterone or its 5alpha-reduced metabolite, dihydrocorticosterone. Conversely, at longer times of exposure (24 h) corticosterone is able to strongly increase FGF-1 mRNA levels. Both effects of corticosterone (inhibition and stimulation) were duplicated by dexamethasone, indicating that both effects occur via the type II receptors. Interestingly, the 5alpha-3alpha-reduced metabolite of deoxycorticosterone, tetrahydrodeoxycorticosterone, which does not interact with either corticosteroid receptors, is able to stimulate (at 6 and 24 h of exposure) the gene expression of FGF-1. It is possible that this effect might be induced via the GABA(A) receptor, since muscimol, an agonist of this receptor, exerts a similar effect. The situation is different in the case of FGF-2. The mRNA levels of this growth factor are only stimulated by steroids interacting with type II receptors. Altogether, these observations indicate that corticosteroids modulate the levels of FGF-1 and FGF-2 gene expression in astroglial cells by interaction with classical (type I and II) or nonclassical (GABA(A) receptor) steroid receptors. PMID- 11211234 TI - Phosphorylation of the common neurotrophin receptor p75 by p38beta2 kinase affects NF-kappaB and AP-1 activities. AB - The signaling pathways invoked by ligand binding to the common neurotrophin receptor p75NTR are incompletely understood. Using the yeast two-hybrid system, we identified the mitogen-activated protein (MAP) kinase p38beta2 as a specific interactor with the 5th and 6th alpha helices of the p75NTR intracytoplasmic region. The consequences of this interaction were studied, using primary cultures of Schwann cells and the 293T cell line. Phosphorylation of p75NTR by p38beta2 was induced in vitro and in vivo by MAP kinase kinases (MKK) 6 activation. This pathway demonstrated feedback in that nerve growth factor (NGF) binding increased p38beta2 activity, causing an increase of nuclear factor-kappaB (NF-kappaB) activation and a decrease of AP-1 activation. The mechanisms described explain at least in part why NGF binding to p75NTR increases cell survival in certain circumstances. PMID- 11211235 TI - Neuroprotective role for the p50 subunit of NF-kappaB in an experimental model of Huntington's disease. AB - Prototypical NF-kappaB consists of a transcription factor dimer of p50 and p65, and an inhibitory subunit called I-kappaB. NF-kappaB is activated in neurons in response to excitotoxic, metabolic, and oxidative stress. Cell-culture data suggest that activation of NF-kappaB can prevent neuronal apoptosis, but its role in vivo is unclear and the specific kappaB subunits involved are unknown. In Huntington's disease (HD), striatal neurons degenerate, and a similar pattern of neuronal vulnerability occurs in rats and mice following exposure to the mitochondrial toxin 3-nitropropionic acid (3NP). We report that mice lacking the p50 subunit of NF-kappaB exhibit increased damage to striatal neurons following administration of 3NP. The neuronal death occurs by apoptosis as indicated by increased caspase activation and DNA fragmentation into oligonucleosomes. NF kappaB activity is markedly increased in striatum 24-72 h following 3NP administration in wild-type mice, but not in mice lacking p50, indicating that p50 is necessary for the vast majority of 3NP-induced NF-kappaB DNA-binding activity in striatum. Cultured striatal neurons from p50-/- mice exhibited enhanced oxidative stress, perturbed calcium regulation, and increased cell death following exposure to 3NP, suggesting a direct adverse effect of p50 deficiency in striatal neurons. PMID- 11211237 TI - Polycyclic aromatic hydrocarbons in placenta. AB - Concentrations of chrysene, benz [a] anthracene, benzo [a]-pyrene, benzo [b] fluoranthene, indeno [1,2,3-c,d] pyrene, dibenz [a,h] anthracene, and benzo [g,h,i] perylene were measured in placentas from 200 women from two cities in Ukraine, Kyiv and Dniprodzerzhinsk. The participants had no special exposures and were chosen from among subjects in an ongoing study of reproductive health. All seven of the polycyclic aromatic hydrocarbons (PAHs) were found in all placentas, with the sole exception of benzo [a] pyrene in one placenta. Chrysene was present at the highest concentrations, with median 1.38 ng/g dry weight. Dibenz [a,h] anthracene and benzo [g,h,i] perylene had the lowest concentrations; each had median 0.73 ng/g dry weight. Concentrations in Kyiv were slightly higher than those in Dniprodzerzhinsk, but the difference was significant only for dibenz [a,h] anthracene. Dibenz [a,h] anthracene and benzo [g,h,i] perylene increased significantly with maternal body mass index, but other PAHs showed no such pattern. Placentas from deliveries in autumn or winter had slightly but not significantly higher concentrations. Concentrations were not related to maternal age. There were too few smokers in the sample for meaningful evaluation. No associations were seen between any of the placental PAH concentrations and birth weight of the infant. PMID- 11211236 TI - Regional hypomyelination and dysplasia in transgenic mice with astrocyte-directed expression of interferon-gamma. AB - Interferon-gamma (IFN-gamma), traditionally associated with a variety of physiological and pathological processes of the immune system, manifests an array of biological effects on cells of the nervous system. Clinical and in vitro studies support a key role for IFN-gamma in the pathogenesis of immune-mediated demyelinating disorders such as multiple sclerosis (MS). To investigate the role of this cytokine within the central nervous system (CNS), transgenic mice were derived in which IFN-gamma transgene expression was selectively targeted to astrocytes, a potentially important cellular source of this cytokine. Here we report that astrocyte-directed expression of IFN-gamma results in regional hypomyelination and selective disruption of brain histogenesis, which included severe cerebellar and hippocampal dysplasia. Transgenic mice were markedly ataxic and the majority died prior to reaching sexual maturity. This study demonstrates that astrocyte-directed expression of IFN-gamma profoundly affects the differentiation and morphogenesis of the brain and provides additional evidence that this cytokine has deleterious consequences on myelin-producing cells, independent of the cellular source. PMID- 11211238 TI - Effect of natural antioxidants and apocynin on LPS-induced endotoxemia in rabbit. AB - The objective of this study was to compare the prophylactic effects of the natural antioxidant from spinach (NAO) and apocynin, on the hepatic oxidative stress and liver damage induced by lipopolysaccharide (LPS). Male New Zealand rabbits were challenged with LPS with or without 8 days of antioxidant pretreatment. Pretreatment with NAO, but not apocynin, significantly (p < 0.05) decreased the levels of hydroperoxides and malondialdehyde (MDA) in the liver cytosolic fraction and the activity of NADPH oxidase-generated superoxide in the microsomal fraction, compared to LPS alone. The activity of glutathione peroxidase (G-POX) was significantly (p < 0.05) increased in the LPS-treated group, whereas treatment with NAO, but not apocynin, significantly (p < 0.05) decreased G-POX activity. Pretreatment with the same antioxidants had no significant effects on superoxide dismutase (SOD) activity, whereas an increased level of catalase (CAT) was obtained in all LPS-treated groups. TUNEL immunohistochemical staining in the LPS-treated animals indicated that there was no increase in apoptosis outside of necrotic foci. However, apoptotic hepatocytes were observed within areas of focal necrosis in animals exposed to LPS alone or LPS plus apocynin. Hepatocyte cell proliferation was tested by the proliferating cell nuclear antigen (PCNA) tool, which indicated a proliferative effect in the LPS group, whereas the effect disappeared in the antioxidant-treated groups. The prophylactic effect of NAO on liver pathology and the significant decreases in lipid peroxidation products and NADPH oxidase activity suggest the use of NAO as an efficient strategy for treatment of endotoxemia. PMID- 11211239 TI - Lack of peripheral neuropathy in Beagle dogs after 53 weeks oral administration of thalidomide capsules. AB - Thalidomide (Thalomid) is approved for use in the US to treat complications from leprosy. Peripheral neuropathy is a dose-limiting adverse event in humans. As part of a nonrodent regulatory toxicology study, Beagle dogs were fed orally via encapsulation for 53 weeks. A component of this study was to determine if the dogs developed peripheral neuropathy. Twenty-eight male and 28 female Beagle dogs approximately 8-10 months of age were used. They were dosed at 43, 200 or 1000 mg/kg for 53 weeks followed by a 4-week treatment-free recovery period. Nerve function was assessed by electrophysiological measurements of the tibial nerve prior to dosing and at weeks 13, 27, 38 and 51. Representative dogs from each group were sacrificed at 26, 53 and 58 weeks and histologic and ultrastructural evaluations were performed on the sural nerve. Thalidomide had no effect on sensory nerve conduction velocity, duration or amplitude of the action potential. At 27 weeks, mean sensory nerve action potential amplitude for females at 43 mg/kg was significantly greater than control but was not evident at 39 weeks. Mean duration of sensory nerve action potential seemed to increase with similar magnitude over time in all dose groups including controls. Histological and ultrastructural evaluation of sections of sural nerve did not identify treatment induced differences between control and thalidomide-dosed animals after 26 and 53 weeks of treatment. Additionally, no differences were observed following a 5-week treatment-free period at week 58. In contrast to humans, Beagle dogs did not develop thalidomide-induced peripheral neuropathy under conditions of the study. PMID- 11211240 TI - Inhibitory effects of the medicinal herb, Thonningia sanguinea, on liver drug metabolizing enzymes of rats. AB - In this study we examined the effect of the aqueous extract of Thonningia sanguinea (T.S.) on 7-ethoxyresorufin O-deethylase (EROD, CYP1A1), 7 pentoxyresorufin O-dealkylase (PROD, CYP2B1/2), 7-methoxyresorufin O-demethylase (MROD, CYP1A2), aniline hydroxylase (aniline, CYP2E1), p-nitrophenol hydroxylase (PNPH, CYP2E1) and erythromycin N-demethylase (ERDM, CYP3A1) in rat liver in vitro and in vivo. Although T.S. extract increased ERDM activity in induced rat liver microsomes, it showed a dose-dependent inhibitory effect in vitro on other P450 monooxygenase activities particularly EROD and PROD, which are mediated primarily by CYP1A1 and CYP2B1/2, respectively. PROD, EROD and MROD activities were also decreased by 18%, 19% and 40%, respectively, in hepatic microsomes prepared from rats treated with T.S. extract for 3 days. Kinetic analysis of CYP activity of 3-methylchloranthrene-induced microsomes demonstrated that T.S. inhibited EROD and MROD activities by a noncompetitive and competitive mechanism, respectively. The analysis of alterations produced by T.S. on PROD kinetic parameters in phenobarbital-induced microsomes suggested that the inhibition is noncompetitive. Pretreatment of rats with T.S. prolonged pentobarbital and phenobarbital sleeping time; however, plasma phenobarbital concentration determined on awakening showed no significant difference between control and T.S. treated rats. T.S. was also found to be a potent inhibitor of the liver cytosolic glutathione S-transferase. These data suggest that selective modulation of CYP isoenzymes by T.S. might contribute to protection of the liver from xenobiotic induced intoxication or to alteration of the action of drug(s) concomitantly administered besides its antioxidative properties. PMID- 11211241 TI - Amelioration of fluoride-induced hypocalcaemia by vitamins. AB - Oral administration of sodium fluoride (40 mg/kg body weight) from day 6 of gestation to day 21 of lactation caused, compared with vehicle control, significantly lowered level of calcium and phosphorus in the serum of both P and F1 generation rats. Administration of vitamin C (50 mg/kg body weight), D (2 ng/0.2 ml olive oil/animal), E (2 mg/0.2 ml olive oil/animal) and a combination (vitamin C + D + E) along with NaF caused significant amelioration in serum calcium in P generation and serum phosphorus in both P and F1 generation rats as compared with only NaF-treated group. Serum calcium concentration was only partially recovered (P and F1 generation) on NaF withdrawal during lactation, as well as, on cotreatment (F1 generation) with vitamins. However, serum phosphorus level was significantly recovered on NaF withdrawal. PMID- 11211242 TI - Comparison of the phagocytic response of rat and hamster alveolar macrophages to man-made vitreous fibers in vitro. AB - Rats and hamsters are well known for their disparate response to inhaled mineral fibers/particles. Alveolar macrophages (AM) play an important role in the pulmonary clearance and retention of mineral fibers/particles mainly through the process of phagocytosis. The aim of this study was to investigate whether there exist differences in the phagocytic response and release of reactive oxygen species (ROS) between rat and hamster AM upon exposure to man-made vitreous fibers (MMVF) in vitro. AM were obtained by bronchoalveolar lavage and macrophage enriched cultures were exposed to MMVF10 and MMVF21 fibers for 20 h. The phagocytic response of macrophages was determined by computer-assisted video microscopy and the superoxide anion production was evaluated by cytochrome c reduction. A significantly higher percentage of rat AM underwent frustrated phagocytosis of both types of MMVF compared to hamster AM. This was associated with a higher ROS release by rat AM compared to hamster AM. These data may help to explain the cellular mechanisms underlying the disparate pulmonary response of rat and hamster to inhaled particulate matter. PMID- 11211243 TI - Astrocyte phenotype and prevention against oxidative damage in neurotoxicity. AB - Astrocytes possess a potent array of protective systems. These are chiefly targeted against oxidised products and radicals, which are frequently present in increased amounts following exposure of nervous tissue to a range of toxic insults. Following exposure to the toxic chemicals astrocytes commonly respond by alteration in phenotype with upregulation of a large number of molecules, including those controlling the protective systems. This article summarizes evidence, largely obtained from in vitro studies, which supports the concept that some of the changes in astrocyte phenotype are associated with increased protection against the cytotoxicity caused by the oxidative damage that results from exposure to range of neurotoxicants. PMID- 11211244 TI - Urinary cotinine levels of smokeless tobacco (Maras powder) users. AB - Smokeless tobacco is used in various forms in some countries of the world. "Maras otu" is a kind of smokeless tobacco usage in the Southeastern region of Turkey. The use of smokeless tobacco causes nicotine addiction and dependence. Moreover this type of smokeless tobacco usage is one of the risk factors for oral cancers and genotoxic damages for users. Cotinine is widely used as a biomarker of tobacco consumption and intake of nicotine. Therefore, urine samples were collected from people who are using Maras powder and smoking cigarettes, and passive smokers, and the levels of cotinine investigated. The purpose of this study is to determine the cotinine levels of Maras powder users and to compare the results with cigarette smokers and passive smokers. Urinary cotinine levels of subjects were determined by using capillary gas chromatography with FID detection. The mean (+/- SD) urinary cotinines have been determined as 6467.35+/ 3198 microg/g creatinine for 26 Maras powder users, 1943.92+/-1443 microg/g creatinine for 26 cigarette smokers and 198.62+/-420.82 microg/g creatinine for 26 passive smokers. A significant difference has been found between cotinine levels of Maras powder users and cigarette smokers, which is three times higher in Maras powder users (p<0.001). The present study suggests that smokeless tobacco poses a threat to public health and it should not be viewed as a safe alternative to cigarettes. PMID- 11211245 TI - Validation of publication of new names and new combinations previously effectively published outside the IJSEM. PMID- 11211246 TI - Thioflavicoccus mobilis gen. nov., sp. nov., a novel purple sulfur bacterium with bacteriochlorophyll b. AB - A novel phototrophic purple sulfur bacterium was isolated from a flat, laminated microbial mat in a salt marsh near Woods Hole, Massachusetts, USA. The cells were monotrichously flagellated motile cocci with internal photosynthetic membranes of the tubular type. The main photosynthetic pigments were bacteriochlorophyll b and the carotenoid 3,4,3',4'-tetrahydrospirilloxanthin. The marine bacterium showed optimal growth in the presence of 2% salts. It was obligately phototrophic and strictly anaerobic. It grew photoautotrophically and photoassimilated acetate, pyruvate and ascorbate as the only organic substrates. In the presence of sulfide, elemental sulfur globules were formed inside the cells. Elemental sulfur was further oxidized to sulfate. The DNA base composition of the new bacterium was 66.5 mol% G+C. The 16S rDNA nucleotide sequence was most similar to strains of Thiococcus pfennigii, there being approximately 92-93% sequence similarity. The new bacterium is described as a new species and a new genus, and the name Thioflavicoccus mobilis is proposed; the type strain is 8321T (= ATCC 700959T). PMID- 11211248 TI - Hyphomicrobium chloromethanicum sp. nov. and Methylobacterium chloromethanicum sp. nov., chloromethane-utilizing bacteria isolated from a polluted environment. AB - Two chloromethane-utilizing facultatively methylotrophic bacteria, strains CM2T and CM4T, were isolated from soil at a petrochemical factory. On the basis of their morphological, physiological and genotypical properties, strain CM2T (= VKM B-2176T = NCIMB 13687T) is proposed as a new species of the genus Hyphomicrobium, Hyphomicrobium chloromethanicum, and strain CM4T (= VKM B-2223T = NCIMB 13688T) as a new species of the genus Methylobacterium, Methylobacterium chloromethanicum. PMID- 11211247 TI - Phylogenetic and DNA-DNA hybridization analyses of Bradyrhizobium species. AB - The 16S rDNA sequence of Bradyrhizobium liaoningense was determined and analysed together with sequences of other Bradyrhizobium species and related taxa. In addition, DNA-DNA hybridizations were performed between representative strains of the three Bradyrhizobium species. Bradyrhizobium liaoningense is genotypically highly related to Bradyrhizobium japonicum, whereas Bradyrhizobium elkanii is more distantly related to these two species. The fact that Afipia, Agromonas, Blastobacter, Nitrobacter and Rhodopseudomonas are phylogenetically more closely related to Bradyrhizobium japonicum than to Bradyrhizobium elkanii is discussed. PMID- 11211249 TI - Clostridium hungatei sp. nov., a mesophilic, N2-fixing cellulolytic bacterium isolated from soil. AB - Two strains of obligately anaerobic, mesophilic, cellulolytic, N2-fixing, spore forming bacteria were isolated from soil samples collected at two different locations near Amherst, MA, USA. Single cells of both strains were slightly curved rods that measured between 2 and 6 microm in length and approximately 0.5 microm in diameter. The spores were spherical, terminally located, distended the sporangium and measured 0.8-1.0 microm in diameter. The cells of both isolates (designated strain ADT and strain B3B) stained Gram-negative, but did not have a typical Gram-negative cell wall structure as demonstrated by transmission electron microscope analysis. The cells of both strains were motile with subpolarly inserted flagella and exhibited chemotactic behaviour towards cellobiose and D-glucose. Both strains fermented cellulose, xylan, cellobiose, cellodextrins, D-glucose, D-xylose, D-fructose, D-mannose and gentiobiose. In addition, strain B3B fermented L-arabinose. For both strains, fermentation products from cellulose were acetate, ethanol, H2 and CO2, as well as small amounts of lactate and formate. The G+C content of strain AD was 40 mol% and that of strain B3B was 42 mol%. Based on their morphological, physiological and phylogenetic characteristics, it was concluded that the two isolates are representatives of a novel species of Clostridium. The name Clostridium hungatei is proposed for the new species. The type strain of Clostridium hungatei sp. nov. is strain ADT (= ATCC 700212T). PMID- 11211250 TI - Desulfosporosinus meridiei sp. nov., a spore-forming sulfate-reducing bacterium isolated from gasolene-contaminated groundwater. AB - Eight strains of spore-forming, sulfate-reducing bacteria, isolated from groundwater contaminated with motor fuel [mostly benzene, toluene ethylbenzene and xylene (BTEX) compounds] in sandy soil near Perth, Australia, were closely related to Desulfosporosinus (previously Desulfotomaculum) orientis DSM 765T (95.3-97.3% 16S rDNA sequence similarity). Whole-cell fatty acids were dominated by even-carbon, straight-chain saturated and mono-unsaturated fatty acids, in particular 16:0, 16:1cis9, 14:0 and 18:1cis11. The strains grew at temperatures between 4 and 42 degrees C and in medium containing up to 4% NaCl. The eight strains clustered into two main groups based on phylogeny, randomly amplified polymorphic DNA (RAPD)-PCR patterns and nutritional characteristics. Representatives of the two groups, strain S5 (group A) and strain S10T (group B) had 81% DNA-DNA homology with each other and therefore should be accommodated in the same species. Strain S10T had less than 38% homology with Desulfosporosinus orientis DSM 765T, the most closely phylogenetically related type strain available. The new strains were distinguished from Desulfosporosinus orientis DSM 765T by different banding patterns in a RAPD-PCR, and phenotypically by their inability to utilize fumarate as a carbon and energy source with sulfate as the electron acceptor and by their lower tolerance to NaCl. The DNA G+C contents were 46.8 and 46.9 mol% for strains S5 and S10T, respectively (Desulfosporosinus orientis DSM 765T 45.9 mol%). It is proposed that these new strains be placed in a new species of the genus Desulfosporosinus. The name Desulfosporosinus meridiei is proposed, with strain S10T as the type strain (= DSM 13257T = NCIMB 13706T). PMID- 11211251 TI - Carboxydobrachium pacificum gen. nov., sp. nov., a new anaerobic, thermophilic, CO-utilizing marine bacterium from Okinawa Trough. AB - A new anaerobic, thermophilic, CO-utilizing marine bacterium, strain JMT, was isolated from a submarine hot vent in Okinawa Trough. Cells of strain JMT were non-motile thin straight rods, sometimes branching, with a cell wall of the Gram positive type, surrounded with an S-layer. Chains of three to five cells were often observed. The isolate grew chemolithotrophically on CO, producing equimolar quantities of H2 and CO2 (according to the equation CO+H2O-->CO2+H2) and organotrophically on peptone, yeast extract, starch, cellobiose, glucose, galactose, fructose and pyruvate, producing H2, acetate and CO2. Growth was observed from 50 to 80 degrees C with an optimum at 70 degrees C. The optimum pH was 6.8-7.1. The optimum concentration of sea salts in the medium was 20.5-25.5 g l(-1). The generation time under optimal conditions was 7.1 h. The DNA G+C content was 33 mol %. Growth of isolate JMT was not inhibited by penicillin, but ampicillin, streptomycin, kanamycin and neomycin completely inhibited growth. The results of 16S rDNA sequence analysis revealed that strain JMT belongs to the Thermoanaerobacter phylogenetic group within the Bacillus-Clostridium subphylum of Gram-positive bacteria but represents a separate branch of this group. On the basis of morphological and physiological features and phylogenetic data, this isolate should be assigned to a new genus, for which the name Carboxydobrachium is proposed. The type species is Carboxydobrachium pacificum; the type strain is JMT (= DSM 12653T). PMID- 11211252 TI - Actinomyces marimammalium sp. nov., from marine mammals. AB - Three strains of a previously undescribed Actinomyces-like bacterium were isolated from samples taken from two dead seals and a porpoise. Biochemical testing and PAGE analysis of whole-cell proteins indicated the strains were phenotypically similar to each other but different from previously described Actinomyces and Arcanobacterium species. Comparative 16S rRNA gene sequencing studies showed the organisms from marine animals were genetically closely related and represent a hitherto unknown subline within the genus Actinomyces (sequence divergence values > 6% with recognized species). Based on phylogenetic and phenotypic evidence it is proposed that the unknown bacterium from the seals and a porpoise should be classified as Actinomyces marimammalium sp. nov. The type strain is CCUG 41710T. PMID- 11211253 TI - Herbaspirillum frisingense sp. nov., a new nitrogen-fixing bacterial species that occurs in C4-fibre plants. AB - The enrichment of nitrogen-fixing bacteria from the C4-fibre plants, Spartina pectinata, Miscanthus sinensis, Miscanthus sacchariflorus and Pennisetum purpureum, with nitrogen-free semi-solid media led to the isolation of Herbaspirillum-like strains among other diazotrophic bacteria. On the basis of physiological properties, phylogenetic analysis comparing 16S rDNA sequences and DNA-DNA hybridization experiments of chromosomal DNA the new isolates could be grouped together in a new species with the proposed name Herbaspirillum frisingense sp. nov. Morphological characteristics, such as cell size and shape, colony appearance, motility and flagellation are largely identical to the known species Herbaspirillum rubrisubalbicans and Herbaspirillum seropedicae. On the basis of utilization of adipate (-), N-acetyl-D-glucosamine (+), meso-erythritol (-), L-rhamnose (-) and meso-inositol (-) Herbaspirillum frisingense sp. nov. can be distinguished from other known Herbaspirillum spp. Nitrogen-fixing capability was examined by PCR amplification of the nifD gene and an acetylene reduction assay, and was found with all isolates tested. 16S rDNA sequence similarity to the other Herbaspirillum spp. is 98.5-99.1%. In genomic DNA-DNA hybridization experiments Herbaspirillum frisingense sp. nov. forms a homogeneous group with 70 100+/-10% similarity, clearly distinct from Herbaspirillum seropedicae and Herbaspirillum rubrisubalbicans with 1-34% similarity. 16S rRNA-targeted oligonucleotide probes, specific for the whole genus Herbaspirillum and for three Herbaspirillum species were designed and are suitable for fluorescence in situ hybridization. The DNA G+C content of Herbaspirillum frisingense sp. nov. is 63+/ 2 mol%, in agreement with the values of 61-65% for the genus. PCR fingerprinting exhibits a consistent pattern for groups of strains isolated from the same plant, suggesting a low genomic diversity among bacteria inhabiting C4-gramineous plant tissues. Low genetic DNA diversity seems to be common between probable endophytic bacterial isolates of the same taxon. The type strain of Herbaspirillum frisingense sp. nov. is GSF30T (= DSM 13128T). PMID- 11211254 TI - Arthrobacter siderocapsulatus Dubinina and Zhdanov 1975AL is a later subjective synonym of Pseudomonas putida (Trevisan 1889) Migula 1895AL. AB - The taxonomic position of Arthrobacter siderocapsulatus Dubinina and Zhdanov 1975AL was investigated using 16S rDNA, fatty acid and phenotypic analyses. The type strain (NCIMB 11286T) showed 99.85% 16S rDNA similarity to the type strain of Pseudomonas putida. Phenotypic properties of the two strains were compared using API 20NE and BIOLOG kits. Identical reactions were recorded for all tests, except for assimilation of malonic acid. The two strains also showed almost identical cellular fatty acid profiles. On the basis of evidence presented in this and earlier studies, it is proposed that Arthrobacter siderocapsulatus is a later subjective synonym of Pseudomonas putida (Trevisan 1889) Migula 1895AL. PMID- 11211256 TI - Reclassification of Desulfobacterium phenolicum as Desulfobacula phenolica comb. nov. and description of strain SaxT as Desulfotignum balticum gen. nov., sp. nov. AB - A mesophilic, sulfate-reducing bacterium (strain SaxT) was isolated from marine coastal sediment in the Baltic Sea and originally described as a 'Desulfoarculus' sp. It used a large variety of substrates, ranging from simple organic compounds and fatty acids to aromatic compounds as electron donors. Autotrophic growth was possible with H2, CO2 and formate in the presence of sulfate. Sulfate, thiosulfate and sulfite were used as electron acceptors. Sulfur and nitrate were not reduced. Fermentative growth was obtained with pyruvate, but not with fumarate or malate. Substrate oxidation was usually complete leading to CO2, but at high substrate concentrations acetate accumulated. CO dehydrogenase activity was observed, indicating the operation of the CO dehydrogenase pathway (reverse Wood pathway) for CO2 fixation and complete oxidation of acetyl-CoA. The rod shaped cells were 0.8-1.0 microm wide and 1.5-2.5 microm long. Spores were not produced and cells stained Gram-negative. The temperature limits for growth were between 10 and 42 degrees C (optimum growth at 28-32 degrees C). Growth was observed at salinities ranging from 5 to 110 g NaCl l(-1), with an optimum at 10 25 g NaCl l(-1). The G+C content of the DNA was 62.4 mol%. Vitamins were required for growth. Based on the 16S rRNA gene sequence, strain SaxT represents a new genus within the delta-subclass of the Proteobacteria. The name Desulfotignum balticum gen. nov., sp. nov. is proposed. After the 16S rDNA sequences of all members of the genus Desulfobacterium were published (GenBank accession nos. AJ237601-AJ237604, AJ237606, AJ237607), the need to reclassify most members of the genus Desulfobacterium became obvious due to their strong phylogenetic affiliation to other genera. Here, we propose to reclassify Desulfobacterium phenolicum as Desulfobacula phenolica comb. nov. Desulfotignum balticum, Desulfobacterium phenolicum and Desulfobacula toluolica contain cellular fatty acids which have so far only been found in members of the genus Desulfobacter. PMID- 11211255 TI - Azospirillum doebereinerae sp. nov., a nitrogen-fixing bacterium associated with the C4-grass Miscanthus. AB - A new group of nitrogen-fixing Azospirillum sp. bacteria was isolated from the roots of the C4-gramineous plant Miscanthus. Polyphasic taxonomy was performed, including auxanography using API galleries, physiological tests and 16S rRNA sequence comparison. The ability of the isolates to fix dinitrogen was evaluated by amplification of the nifD gene, immunodetection of the dinitrogenase reductase and acetylene-reduction assay. On the basis of these results, the nitrogen-fixing isolates represent a new species within the genus Azospirillum. Its closest phylogenetic neighbours, as deduced by 16S rDNA-based analysis, are Azospirillum lipoferum, Azospirillum largimobile and Azospirillum brasilense with 96.6, 96.6 and 95.9% sequence similarity, respectively. Two 16S rRNA-targeting oligonucleotide probes were developed which differentiate the new species from the other Azospirillum species by whole-cell fluorescence hybridization. Strains of the new species are curved rods or S-shaped, 1.0-1.5 microm in width and 2,0 3.0 microm in length, Gram-negative and motile with a single polar flagellum. Optimum growth occurs at 30 degrees C and at pH values between 6.0 and 7.0. No growth takes place at 37 degrees C. They have a respiratory type of metabolism, grow well on arabinose, D-fructose, gluconate, glucose, glycerol, malate, mannitol and sorbitol. They differ from A. largimobile and A. lipoferum by their inability to use N-acetylglucosamine and D-ribose, from A. lipoferum by their ability to grow without biotin supplementation and from A. brasilense by their growth with D-mannitol and D-sorbitol as sole carbon sources. Nitrogen fixation occurs in microaerobic nitrogen-limited conditions. For this species, the name Azospirillum doebereinerae sp. nov. is suggested, with strain GSF71T as the type strain (= DSM 13131T; reference strain Ma4 = DSM 13400). Its G+C content is 70.7 mol%. PMID- 11211257 TI - Phylogenetic position of Bartonella vinsonii subsp. arupensis based on 16S rDNA and gltA gene sequences. AB - The nucleotide sequences of the genes encoding 16S rRNA and citrate synthase (gltA) from a recently described member of the genus Bartonella, Bartonella vinsonii subsp. arupensis, isolated from mice and from the blood of a patient suffering from bacteraemia, were determined and compared with sequences of the 16S rDNA and gltA genes of other members of the genus Bartonella in order to determine its relative phylogenetic position. B. vinsonii subsp. arupensis appeared to be closely related to B. vinsonii subsp. vinsonii, another rodent associated taxon, and to B. vinsonii subsp. berkhoffii, which was described recently in dogs. PMID- 11211258 TI - Genotypic and chemotaxonomic evidence for the reclassification of Pseudomonas woodsii (Smith 1911) Stevens 1925 as Burkholderia andropogonis (Smith 1911) Gillis et al. 1995. AB - It was reported before that [Pseudomonas] woodsii and Burkholderia andropogonis are phenotypically indistinguishable and probably represent the same taxon, for which the name B. andropogonis has been proposed. In the present study, it was found that [P.] woodsii and B. andropogonis strains were indistinguishable by whole-cell protein electrophoresis and have a highly similar cellular fatty acid composition. A high DNA-DNA binding value of 95% was found between the type strains of both species. In addition, the 16S rDNA sequence of [P.] woodsii strain LMG 2362T was very similar to that of B. andropogonis LMG 2129T (99.0%). The chemotaxonomic and genotypic data confirm that [P.] woodsii and B. andropogonis represent the same species, for which it is proposed to retain the name B. andropogonis. PMID- 11211259 TI - Amycolatopsis sacchari sp. nov., a moderately thermophilic actinomycete isolated from vegetable matter. AB - The taxonomic position of a group of moderately thermophilic actinomycetes isolated from vegetable matter was determined using a suite of genotypic and phenotypic properties. The organisms were found to share a range of chemical and morphological markers typical of members of the genus Amycolatopsis. A representative of the group, strain K24T, formed a distinct phyletic line within the range of variation occupied by the genus Amycolatopsis in the 16S rDNA tree. The strains have many phenotypic properties in common and some of these distinguish the group from representatives of the validly described species of Amycolatopsis. It is clear from the combined datasets that the strains merit recognition as a new species of Amycolatopsis. The name proposed for the new species is Amycolatopsis sacchari; the type strain is K24T (= DSM 44468T = KCTC 9863T). PMID- 11211260 TI - Phylogeny of the filamentous bacterium 'Nostocoida limicola' III from activated sludge. AB - Five strains of the filamentous bacterium 'Nostocoida limicola' III were successfully isolated into pure culture from samples of activated sludge biomass from five plants in Australia. 16S rRNA gene sequence analyses showed that all isolates were members of the Planctomycetales, most closely related to Isosphaera pallida, but they differed phenotypically from this species in that they did not glide and were not thermotolerant. The ultrastructure of these 'N. limicola' III isolates was also consistent with them being Planctomycetales, in that they possessed complex intracellular membrane systems compartmentalizing the cells. However, the arrangements of these intracellular membranes differed between isolates. These data confirm that 'N. limicola' III is phylogenetically unrelated to both 'N. limicola' I and 'N. limicola' II, activated sludge filamentous bacteria which share morphological features in common with 'N. limicola' III and which have been presumed historically to be the same or very similar bacteria. PMID- 11211262 TI - Taxonomic studies on the genus Cystofilobasidium: description of Cystofilobasidium ferigula sp. nov. and clarification of the status of Cystofilobasidium lari-marini. AB - A new species of the genus Cystofilobasidium is described as Cystofilobasidium ferigula sp. nov. The new taxon represents the teleomorphic stage of Cryptococcus ferigula and was obtained in mating experiments using three strains deposited in the Portuguese Yeast Culture Collection (mating types A1) and a recent isolate (mating type A2). Cystofilobasidium ferigula is characterized using an integrated approach encompassing morphological studies, investigation of the ultrastructure of the septal pore, a comparative study of physiological traits, determination of the DNA base composition, DNA reassociation experiments and PCR fingerprinting. During the course of this study, a close similarity of microsatellite-primed PCR fingerprints was detected between Cystofilobasidium lari-marini and Cystofilobasidium capitatum. DNA-DNA reassociation experiments gave high homology values, which indicates that Cystofilobasidium lari-marini must be regarded as a synonym of Cystofilobasidium capitatum. PMID- 11211261 TI - Molecular evolution of the Chlamydiaceae. AB - Phylogenetic analyses of surface antigens and other chlamydial proteins were used to reconstruct the evolution of the Chlamydiaceae. Trees for all five coding genes [the major outer-membrane protein (MOMP), GroEL chaperonin, KDO transferase, small cysteine-rich lipoprotein and 60 kDa cysteine-rich protein] supported the current organization of the family Chlamydiaceae, which is based on ribosomal, biochemical, serological, ecological and DNA-DNA hybridization data. Genetic distances between some species were quite large, so phylogenies were evaluated for robustness by comparing analyses of both nucleotide and protein sequences using a variety of algorithms (neighbour-joining, maximum-likelihood, maximum-parsimony with bootstrapping, and quartet puzzling). Saturation plots identified areas of the trees in which factors other than relatedness may have determined branch attachments. All nine species were clearly differentiated by distinctness ratios calculated for each gene. The distribution of virulence traits such as host and tissue tropism were mapped onto the consensus phylogeny. Closely related species were no more likely to share virulence characters than were more distantly related species. This phylogenetically disjunct distribution of virulence traits could not be explained by lateral transfer of the genes we studied, since we found no evidence for lateral gene transfer above the species level. One interpretation of this observation is that when chlamydiae gain access to a new niche, such as a new host or tissue, significant adaptation ensues and the virulence phenotype of the new species reflects adaptation to its environment more strongly than it reflects its ancestry. PMID- 11211263 TI - Sporobolomyces yunnanensis sp. nov., a Q-10(H2)-containing yeast species with a close phylogenetic relationship to Erythrobasidium hasegawianum. AB - A ballistoconidia-forming yeast strain, CH 2.141T, isolated from a semi-dried leaf sample collected in Yunnan, China, was found to have Q-10(H2) as its major ubiquinone. Molecular phylogenetic analysis based on the nucleotide sequences of small subunit (18S) rDNA and the internal transcribed spacer region (including 5.8S rDNA) indicated that the strain was closely related to the two described Q 10(H2)-containing yeast species, Erythrobasidium hasegawianum and Sporobolomyces elongatus, with a closer relationship to the former. A DNA-DNA reassociation experiment showed that strain CH 2.141T represents a new yeast species, for which the name Sporobolomyces yunnanensis sp. nov. is proposed. PMID- 11211264 TI - Phylogenetic structure of the Sporopachydermia cereana species complex. AB - A large number of isolates previously referred to as members of the 'Sporopachydermia cereana species complex' were examined by various DNA characterization methods, leading to the conclusion that the complex is in fact made up of 10 species, one of which contains three varieties. The sequences of the internal transcribed spacer (ITS) region and the D1/D2 divergent domains of the large subunit rDNA were determined for representatives of each taxon and specific primers based on differences in the ITS were designed for rapid identification of five of the taxa. Whereas the data provide additional elements for the calibration of the ITS as a criterion for species delineation, the emerging pattern is that the ITS region does not function as well as the D1/D2 domains as an evolutionary clock. Some taxa appear to be specific for the geographical regions where they were isolated, and the distribution of many taxa is mutually exclusive. PMID- 11211266 TI - A taxonomic note on the authorship and date of valid publication of Rhodococcus sputi. AB - Authorship of the name Rhodococcus sputi is variously attributed to Tsukamura 1978 or Tsukamura and Yano 1985. DNA-DNA binding data indicate that this species and Rhodococcus obuensis Tsukamura 1983 and Rhodococcus chubuensis Tsukamura 1983 are subjective (heterotypic) synonyms. Although these organisms have been placed in the genus Gordonia as Gordonia sputi, the correct name of the taxon created by unification of these three species is directly affected by the date of valid publication of these species as members of the genus Rhodococcus. Thus, the name R. sputi only has priority if the authorship is attributed to Tsukamura 1978. The question of authorship and priority is clarified in the present work. PMID- 11211265 TI - Radical changes to chlamydial taxonomy are not necessary just yet. PMID- 11211267 TI - Determination of the systematic position of the genus Asticcacaulis Poindexter by a polyphasic analysis. AB - The genus Asticcacaulis, to date, comprises two species of unicellular, stalked bacteria, developing a stalk at a site which is not coincidental with the centre of the pole of the cell. Multiplication is similar to that demonstrated by the prosthecate species of the genera Caulobacter, Brevundimonas and Maricaulis. A polyphasic approach, comprising 16S rRNA gene sequencing, lipid analysis and NaCl tolerance characterizations, was used to clarify the taxonomy of the two Asticcacaulis species. From the analysis of the 16S rRNA gene sequences, a close phylogenetic relationship between the species that comprise the genera Asticcacaulis, Caulobacter and Brevundimonas could be deduced wherein the three genera form three distinct branches. The individual genera could also be discerned by different characteristic polar lipids. The species of Asticcacaulis differed from species of Caulobacter and Brevundimonas by the lack of 1,2-diacyl 3-O-[6'-phosphatidyl-alpha-D-glucopyranosyl]glycerol. They also did not contain 1,2-di-O-acyl-3-O-[D-glucopyranosyl-(1-->4)-alpha-D-glucuronopyranosyl]glycerol, which is found in most Brevundimonas species but not in strains of the genus Caulobacter. The morphological differences seen between the two species Asticcacaulis excentricus and Asticcacaulis biprosthecium are mirrored by the observed 16S rDNA sequence similarity value of 95.3%, which is relatively low compared to the interspecies similarity values observed within the genera Brevundimonas or Caulobacter. PMID- 11211268 TI - Genomic approaches to typing, taxonomy and evolution of bacterial isolates. AB - The current literature on bacterial taxonomy, typing and evolution will be critically examined from the perspective of whole-genome structure, function and organization. The following three categories of DNA band pattern studies will be reviewed: (i) random whole-genome analysis; (ii) specific gene variation and (iii) mobile genetic elements. (i) The use of RAPD, PFGE and AFLP to analyse the whole genome will provide a skeleton of polymorphic sites with exact genomic positions as whole-genome sequence data become available. (ii) Different genes provide different levels of evolutionary information for determining isolate relatedness depending on whether they are highly variable (prone to recombination events and horizontal transfer), housekeeping genes with only a small number of single nucleotide differences between isolates or part of the rrn multigene family that is prone to intragenomic recombination and concerted evolution. Comparative analyses of these different gene classes can provide enhanced information about isolate relatedness. (iii) Mobile genetic elements such as insertion sequences, transposons, plasmids and bacteriophages integrate into the bacterial genome at specific (e.g. tRNA genes) or non-specific sites to alter band patterns produced by PFGE, RAPD or AFLP. From the literature it is not clear what level of genetic element duplication constitutes non-relatedness of isolates. A model is presented that incorporates all of the above genomic characteristics for the determination of isolate relatedness in taxonomic, typing and evolutionary studies. PMID- 11211269 TI - Reclassification of bioindicator strains Bacillus subtilis DSM 675 and Bacillus subtilis DSM 2277 as Bacillus atrophaeus. AB - On the basis of high DNA-DNA reassociation values and confirmatory automated RiboPrint analysis, two aerobic spore-forming strains hitherto allocated to Bacillus subtilis and used as bioindicators (DSM 675, hot-air sterilization control; DSM 2277, ethylene oxide sterilization control) are reclassified as Bacillus atrophaeus. PMID- 11211270 TI - Clostridium hiranonis sp. nov., a human intestinal bacterium with bile acid 7alpha-dehydroxylating activity. AB - The Clostridium-like organisms TO-931T and HD-17, isolated from human faeces, have high levels of bile acid 7alpha-dehydroxylating activity. Sequencing of their 16S rDNA demonstrated that they belong to cluster XI of the genus Clostridium and that they represent a new and distinct line of descent. Clostridium bifermentans and Clostridium sordellii in cluster XI also possess bile acid 7alpha-dehydroxylating activity. DNA-DNA hybridization experiments with the isolates, TO-931T and HD-17, and C bifermentans and C. sordellii revealed that the isolates are a single species distinct from C. bifermentans and C sordellii. On the basis of phylogenetic analysis, using 16S rDNA sequences, and DNA-DNA hybridization analysis, it is concluded that strains TO-931T and HD-17 are members of a new species of the genus Clostridium, for which the name Clostridium hiranonis is proposed. The type strain is strain TO-931T (= JCM 10541T = DSM 13275T). PMID- 11211271 TI - Lactobacillus cypricasei sp. nov., isolated from Halloumi cheese. AB - Four strains of a hitherto unknown bacterium isolated from Halloumi cheese were compared by using phenotypic and phylogenetic studies. Comparative 16S rRNA gene sequencing demonstrated that the strains were identical to each other and represent a new subline within the genus Lactobacillus. The unknown bacterium was readily distinguished from other described Gram-positive catalase-negative taxa by means of biochemical tests and electrophoretic analysis of whole-cell proteins. On the basis of phylogenetic and phenotypic evidence, it is proposed that the unknown bacterium be classified as Lactobacillus cypricasei sp. nov. The type strain of L. cypricasei is CCUG 42961T (= CIP 106393T). PMID- 11211272 TI - Re-examining the 16S rDNA sequence of Halomonas salina. AB - Previous reports of 16S rDNA sequencing of members of the family Halomonadaceae Franzmann et al. 1989 include two different sequences that were both attributed to the type strain of Halomonas salina (Valderrama et al. 1991) Dobson and Franzmann 1996 (basonym Deleya salina Valderrama et al. 1991). The two sequences are sufficiently different for them to belong to two different species within the genus Halomonas. In order to determine which of the two sequences corresponded to that of the type strain of Halomonas salina, the designated type strains of this species were obtained from the ATCC and the DSMZ. It was possible to show that only one of the previous sequences corresponded to the sequences obtained from DSMZ 5928T and ATCC 49509T. PMID- 11211273 TI - Arcanobacterium pluranimalium sp. nov., isolated from porpoise and deer. AB - Two strains of a previously undescribed Arcanobacterium-like bacterium were isolated from a dead harbour porpoise and a dead sallow deer. Biochemical testing and PAGE analysis of whole-cell proteins indicated that the strains were phenotypically closely related to each other and distinct from previously described Actinomyces and Arcanobacterium species. Comparative 16S rRNA gene sequencing studies showed the bacterium to be a hitherto unknown subline within the genus Arcanobacterium. Based on phylogenetic and phenotypic evidence, it is proposed that the unknown bacterium be classified as Arcanobacterium pluranimalium sp. nov. The type strain of Arcanobacterium pluranimalium is CCUG 42575T (= CIP 106442T). PMID- 11211274 TI - Vibrio cyclotrophicus sp. nov., a polycyclic aromatic hydrocarbon (PAH)-degrading marine bacterium. AB - Strain P-2P44T was isolated from creosote-contaminated marine sediments by using a most-probable number procedure in which phenanthrene was the sole carbon and energy source. Growth experiments showed that P-2P44T utilized several two- and three-ring polycyclic aromatic hydrocarbons (PAHs) as substrates, including naphthalene, 2-methylnaphthalene and phenanthrene. Additionally, gas chromatography experiments showed that P-2P44T degraded several other PAHs, though it was unable to use them as sole sources of carbon and energy. Phylogenetic analyses confirmed that strain P-2P44T is a member of the genus Vibrio, most closely related to Vibrio splendidus. However, strain P-2P44T shared only 98.3% 16S rDNA identity and 35% DNA-DNA reassociation with the type strain of V. splendidus. Strain P-2P44T differed phenotypically from V. splendidus. Together, these differences indicated that strain P-2P44T represents a novel species in the genus Vibrio, for which the name Vibrio cyclotrophicus sp. nov. is proposed; the type strain is P-2P44T (= ATCC 700982T = PICC 106644T). PMID- 11211275 TI - Reclassification of [Pseudomonas] doudoroffii (Baumann et al. 1983) into the genus Oceanomonas gen. nov. as Oceanomonas doudoroffii comb. nov., and description of a phenol-degrading bacterium from estuarine water as Oceanomonas baumannii sp. nov. AB - A bacterium, isolate GB6T, capable of degrading phenol in the presence of elevated salinity was isolated from the estuary of the River Wear, UK. The bacterium was subjected to biochemical and molecular analysis to determine its taxonomic status. These studies indicated that the bacterium was a distinct species closely related to [Pseudomonas] doudoroffii. However, the phylogenetic analysis indicated that [Pseudomonas] doudoroffii was misclassified, as noted previously. Analysis of the characteristics of isolate GB6T and the type strain of [Pseudomonas] doudoroffii confirmed that these bacteria belonged to the same novel genus, which we have named Oceanomonas gen. nov. The type strain of Oceanomonas doudoroffii (Baumann et al. 1983) comb. nov. is ATCC 27123T (= DSM 7028T. The DNA-DNA homology between isolate GB6T and [Pseudomonas] doudoroffii is low and phenotypic differences between the two organisms are evident. Isolate GB6T (= ATCC 700832T = NCIMB 13685T) is therefore proposed as the type strain of a new species, Oceanomonas baumannii sp. nov. PMID- 11211276 TI - Sphingomonas alaskensis sp. nov., a dominant bacterium from a marine oligotrophic environment. AB - Seven Gram-negative strains, isolated in 1990 from a 10(6)-fold dilution series of seawater from Resurrection Bay, a deep fjord of the Gulf of Alaska, were identified in a polyphasic taxonomic study. Analysis of 16S rDNA sequences and DNA-homology studies confirmed the phylogenetic position of all strains in the genus Sphingomonas and further indicated that all of the strains constitute a single homogeneous genomic species, distinct from all validly described Sphingomonas species. The ability to differentiate the species, both phenotypically and chemotaxonomically, from its nearest neighbours justifies the proposal of a new species name, Sphingomonas alaskensis sp. nov., for this taxon. Strain LMG 18877T (= RB2256T = DSM 13593T) was selected as the type strain. PMID- 11211277 TI - Ornithinimicrobium humiphilum gen. nov., sp. nov., a novel soil actinomycete with L-ornithine in the peptidoglycan. AB - A Gram-positive bacterium originating from garden soil was taxonomically studied. Cells are non-motile, non-sporulating, irregular rods and cocci. The cell wall peptidoglycan contains L-ornithine as diagnostic diamino acid and an interpeptide bridge consisting of L-Orn<--L-Ala<--Gly<--D-Asp. The major menaquinone is MK 8(H4). 13-Methyl tetradecanoic acid and 14-methyl pentadecanoic acid are the predominant fatty acids. The polar lipids are phosphatidylinositol, phosphatidylglycerol, diphosphatidylglycerol, three unknown glycolipids and three unknown phospholipids. Mycolic acids are absent. The DNA G+C composition is 70 mol%. The acyl type of the glycan chain of peptidoglycan is acetyl. Glucose is the dominating whole cell sugar; arabinose, rhamnose and xylose are present in traces. Results of 16S rDNA sequence comparisons revealed that strain HKI 0124T represents a novel lineage within the suborder Micrococcineae of the order Actinomycetales adjacent to the recently described genus Ornithinicoccus. On the basis of the clearly pronounced morphological, physiological, chemotaxonomic and phylogenetic differences between strain HKI 0124T and all members of the suborder Micrococcineae, it is proposed to assign strain HKI 0124T to a new genus and species, Ornithinimicrobium humiphilum gen. nov., sp. nov. The type and only strain is HKI 0124T (= DSM 12362T = CIP 106634T). PMID- 11211279 TI - Factors differentiating women and men who successfully maintain weight loss from women and men who do not. AB - The current study explored the relative contribution of exercise, coping responses, cognitive attributions, and emotional experiences to successful weight loss maintenance in men and women. The data were collected via a large community based survey on dieting and weight loss commissioned by Consumer Union. Men and women who met our criteria for successful (n = 277 men, n = 329 women) and unsuccessful (n = 277 men, n = 329 women) weight-loss maintenance were included in the sample. Successful weight-loss maintainers (Maintainers) reported having lost at least 10% of their highest adult weight and having maintained that weight loss for at least the three years immediately prior to the survey. Unsuccessful weight-loss maintainers (Regainers) reported not ever having been able to maintain a significant weight loss and having lost and regained a minimum of 10 to 19 pounds at least once. In response to a dietary lapse, Maintainers, as compared with Regainers, reported being more likely to use direct coping and less likely to seek help. The results imply that the most useful variables for differentiating between successful and unsuccessful weight-loss maintainers may involve how they respond to a dietary lapse. PMID- 11211278 TI - A revision of Rhizobium Frank 1889, with an emended description of the genus, and the inclusion of all species of Agrobacterium Conn 1942 and Allorhizobium undicola de Lajudie et al. 1998 as new combinations: Rhizobium radiobacter, R. rhizogenes, R. rubi, R. undicola and R. vitis. AB - Rhizobium, Agrobacterium and Allorhizobium are genera within the bacterial family Rhizobiaceae, together with Sinorhizobium. The species of Agrobacterium, Agrobacterium tumefaciens (syn. Agrobacterium radiobacter), Agrobacterium rhizogenes, Agrobacterium rubi and Agrobacterium vitis, together with Allorhizobium undicola, form a monophyletic group with all Rhizobium species, based on comparative 16S rDNA analyses. Agrobacterium is an artificial genus comprising plant-pathogenic species. The monophyletic nature of Agrobacterium, Allorhizobium and Rhizobium and their common phenotypic generic circumscription support their amalgamation into a single genus, Rhizobium. Agrobacterium tumefaciens was conserved as the type species of Agrobacterium, but the epithet radiobacter would take precedence as Rhizobium radiobacter in the revised genus. The proposed new combinations are Rhizobium radiobacter, Rhizobium rhizogenes, Rhizobium rubi, Rhizobium undicola and Rhizobium vitis. PMID- 11211280 TI - Further results on the reliability of the Parental Bonding Instrument (PBI) in an Italian sample of schizophrenic patients and their parents. AB - The reliability of the Italian version of the Parental Bonding Instrument (PBI) was assessed in a group of 26 schizophrenic patients and their parents. In both groups, internal consistency indices were satisfactory and mean PBI scores at test and retest were stable. The test-retest reliability coefficients for the PBI scales of parents ranged from .65 to .67, those of the patients from .32 (paternal-protection score) to .67 (maternal-care score). The less satisfactory test-retest reliability of patients' paternal protection score was due to minor intra-category rather than inter-category variations in their ratings. This suggests difficulties with a four-point rating scale, which might depend partly on the generally poor schooling of the sample, but it may also reflect uncertainty of schizophrenic patients concerning fathers' controlling behavior. Further studies should pay attention to this factor. Patients' PBI mean scores are compatible with an affection-less control rearing style, while those of their parents, characterized by similar poor care but less control, are consistent with a pattern of weak parental bonding. PMID- 11211281 TI - Coping and catastrophizing in chronic pain: a psychometric analysis and comparison of two measures. AB - We analyzed and compared the psychometric properties of two measures of strategiesfor coping with pain:The Coping Strategies Questionnaire (CSQ) and the Cognitive Coping Strategies Inventory (CCSI). The CSQ and CCSI were repeatedly administered to 30 chronic pain patients. Several subscales of both measures showed inadequate internal consistency, and test-retest (one week interval) reliability lower than 0.7. For each inventory, moderate to strong intercorrelations between several subscales were observed. The Catastrophizing subscale was the only subscale for which there was clear evidence of construct validity. Results indicated that both measures showed similar psychometric difficulties, and question the construct validity of subscales other than Catastrophizing. Catastrophizing, however, more closely reflects appraisal processes than a coping strategy per se. We suggest that measures that use more parsimonious and empirically derived coping strategy subscales and that also assess appraisal factors would assist in advancing our understanding of coping with chronic pain. PMID- 11211282 TI - Item characteristics of the Michigan Alcoholism Screening Test. AB - Items of the Michigan Alcoholism Screening Test (MAST) were individually evaluated regarding disproportional responding. The item with the lowest degree of endorsement (Item 18, related to liver problems) was found to have correspondingly low relationships with other MAST items and with the total score. Weighted items concerned with drug-related arrests were found to detract from the otherwise relatively homogeneous MAST items. Traditional statistical approaches for homogeneity suggest high level internal consistency with the deletion of the aforementioned items. A factor analytic test of homogeneity was confirmed. Recommendations are presented concerning modification of the MAST scoring procedures. PMID- 11211283 TI - A content analysis of smoking craving. AB - The purpose of this study was to conduct a content analysis of smoking craving in order to investigate more precisely the subjective nature of the construct with the goal of informing assessment. Thirty-two smokers interested in cessation treatment provided free response written descriptions of the level of craving they normally experience. These responses were analyzed for subjective content along five theoretical domains: physiological, affective, cognitive, behavioral, and synonyms (of craving). Although there were no differences in the relative proportion of broad content terms smokers used to describe their craving (e.g., cognitive versus affective), this analysis revealed considerable diversity in the specific terms smokers used. Some smokers described their craving in purely physiological terms whereas others used primarily cognitive terms, and still others used affective terms. To assume that smoking craving is qualitatively similar across persons, then, may mask important variations that define the individual experience of craving. PMID- 11211284 TI - Placebo insight: the rationality of insight-oriented psychotherapy. AB - It is widely believed that the insight-oriented psychotherapies provide their clients with valid methods of self-exploration that lead to bona fide self knowledge. It also is widely believed that clients' insights must be true in order to be therapeutically effective. Both these claims are implausible. I argue that because clients face significant epistemic pressures in the therapeutic encounter, the insight-oriented psychotherapies are highly susceptible to generating placebo insights, that is, illusions, deceptions, and adaptive self misunderstandings that convincingly mimic veridical insight but have no genuine explanatory power. The insight-oriented psychotherapies also are highly susceptible to generating therapeutic artefacts that appear to confirm the insights acquired by clients. The powerful treatment methods to which clients are subjected generate some of the very psychological and behavioral facts that clients claim to "discover" in their explorations. This impugns the scientific status of the insight-oriented psychotherapies. PMID- 11211285 TI - Introduction: antiscientific attitudes within psychotherapy: philosophical, scientific, and political/psychological considerations. PMID- 11211286 TI - Dangers of anecdotal reports. AB - The anecdotal case study tradition in psychoanalysis has a long, hallowed history and continues to seem the best way to describe our clinical encounters. But reliance on memory in the absence of witnesses or other kinds of corroboration (such as audio recording) can (a) protect standard theory from necessary corrections; (b) lead to the underreporting of technical mistakes, outright clinical failures, and, paradoxically, innovative approaches; (c) tempt us to substitute, by way of narrative smoothing, what ought to happen for what actually transpired; and (d) lead to the loss of an invaluable, one-of-a-kind set of observations that can never be replaced. PMID- 11211287 TI - Antiscientific attitudes: what happens when scientists are unscientific? AB - Scientists sometimes engage in quite unscientific behavior in order to influence their peers or to obtain secondary gain. We explore some of the causes and consequences of these acts, using examples of different ways in which antiscientific attitudes are manifest among scientists. PMID- 11211288 TI - Antiscientific attitudes within psychotherapy: concluding comments. AB - In all of the articles of this special section (Beutler & Harwood, Erwin, Jopling, and Spence), the authors express their commitment to a conventional view of truth and objectivity, a view which serves as a precondition for their commitment to a true science of psychotherapy. In my concluding comments, I first describe the particular focus of each author's concerns about current standards of truth and objectivity in the field. I then anticipate the ways in which their arguments might be challenged by those who now challenge the possibility of truth and objectivity (in any conventional sense) within psychotherapy, or, more broadly, within the human sciences, or, more radically, within the physical sciences. PMID- 11211290 TI - The rejection of natural science approaches to psychotherapy: language and the world. AB - Many postmodernists appeal to theses about the relationship between language and reality as one basis for rejecting natural science approaches to psychotherapy. The theses include one or more of the following: (a) There are multiple worlds rather than just one, (b) worlds are constructed rather than discovered, and (c) worlds are not independent of mind and language. I refer to the conjunction of these three propositions as the multiple worlds-constructionist view. After examining the most systematic defense of the multiple worlds-constructionist view. I conclude that it fails, and that each component of the view is false. PMID- 11211289 TI - A comparison of dose-response curves in cognitive-behavioral and psychodynamic psychotherapies. AB - Changes in patient- and therapist-rated process items, and patient-rated symptom severity assessed over a maximum of 30 sessions of psychodynamic or cognitive behavioral psychotherapy were compared in an outpatient mental-health clinic. Patients' ratings in psychodynamic psychotherapy on two of the process items were superior to ratings by patients in cognitive-behavioral therapy, and interactions with time were discovered for an interpersonal item. Comparisons between patients who reported their initial symptom severities as most severe and those with less severe symptoms also were made, with results indicating differential effects of treatment according to perceptions of symptom severity. Interactions between length of stay in treatment and number of sessions also were investigated. Findings indicated that patients benefit from psychotherapy over time and support the usefulness of a contextual model for psychotherapy funding. PMID- 11211291 TI - Social problem-solving abilities and personality disorder characteristics among dual-diagnosed persons in substance abuse treatment. AB - We examined the relation of self-appraised social problem-solving abilities and personality-disorder characteristics to the adjustment and compliance of persons with dual diagnoses in substance-abuse treatment. It was hypothesized that elements of the problem-orientation component would remain predictive of depressive behavior and distress after considering personality-disorder characteristics among 117 persons receiving inpatient-substance-abuse treatment. Furthermore, self-appraised problem-solving abilities were expected to predict the occurrence of "dirty" drug and alcohol screens during treatment and compliance with the first scheduled community follow-up visit. Results supported predictions concerning the relation of problem-solving confidence to depressive behavior, distress, and substance-use screens; however, a paradoxical relation was observed between the problem-orientation variables and compliance with the first outpatient visit. The results are interpreted within the context of contemporary models of social problem solving and the implications for cognitive behavioral assessment and intervention are considered. PMID- 11211292 TI - Couple functioning in depression: the roles of sociotropy and autonomy. AB - We evaluated the hypothesis that interpersonal relationships of depressed persons would vary as a function of the personality variables sociotropy and autonomy. Depressed psychiatric patients who reported being in a current intimate relationship for at least six months were administered measures of sociotropy, autonomy, and several aspects of relationship functioning. Results indicated that sociotropy was related significantly to patients' reporting their own behavior as demanding and their partners' behavior as withdrawing, whereas autonomy was related to patients' reporting their partners' behavior as demanding and their own behavior as withdrawing. Autonomy also was related to greater relationship dissatisfaction, and there was a trend for autonomy to be related to greater criticism of the partner. The results are consistent with a model in which sociotropy and autonomy increase vulnerability to depression, in part, through their effects on interpersonal relationships. PMID- 11211293 TI - Transmigrant mandibular canines: a record of 28 cases and a retrospective review of the literature. AB - The transmigrant mandibular canine is a rare phenomenon. Most authors have described singular cases of unilateral or bilateral occurrence; however, a few authors have published more cases. This paper describes 28 cases exhibiting transmigratory canines. The observations are compared with observations from 39 earlier reports. Women are affected more than men. The left canine undergoes transmigration more commonly than does the right canine. Transmigration and impaction appear to be more common. Most of the patients do not have any symptoms, and these canines are often discovered at the radiological examination before orthodontic treatment. The etiology is obscure; however, abnormal displacement of the tooth bud in embryonic life is a commonly accepted explanation. Prolonged retention of the deciduous canine is a good clinical sign for a thorough radiological examination, preferably including an orthopantomographic radiograph. This would help in preventive measures. However, once established, a transmigrated canine requires surgical extraction. If possible, and if space is available and the patient is willing, all orthodontic efforts should be made to restore the normal position of this functionally very useful tooth in the human dentition. PMID- 11211294 TI - Obstructive sleep apnea: a canonical correlation of cephalometric and selected demographic variables in obese and nonobese patients. AB - One hundred male obstructive sleep apnea (OSA) patients were classified into 2 groups on the basis of body mass index (BMI): 43 nonobese (BMI < 30 kg/m2) and 57 obese (BMI > or = 30 kg/m2) patients. A comprehensive cephalometric analysis with a multivariate statistical method was performed in order to define the different principal components (PCs) of cervico-craniofacial skeletal and upper airway soft tissue morphology in each group and how they contributed to selected elements of the patient demographic data, ie, apnea-hypopnea index (AHI), nocturnal oxyhemoglobin saturation, and BMI. Thirty cephalometric variables of cervico craniofacial skeletal morphology were reduced to 8 PCs describing 84.4% and 85.4% of the total variance in obese and nonobese OSA patients, respectively. Sixteen cephalometric variables of hyoid bone position and head posture were reduced to 4 PCs describing 84.4% and 85.9% of the total variance in obese and nonobese OSA patients, respectively. Twenty cephalometric variables of upper airway soft tissue morphology were reduced to 7 PCs describing 89.5% and 84.6% of the total variance in obese and nonobese OSA patients, respectively. For further analysis of PCs, a stepwise multiple regression analysis was chosen. Two dependent variables of interest are the minimal distance of the posterior pharyngeal airway space (PASmin) and AHI. PASmin accounted for 95.3% (obese OSA group) and 74.3% (nonobese OSA group) with 7 PCs and AHI for 46% with 3 PCs in both groups. Three canonical variables and their correspondents with different loadings were established differently for both OSA groups. A canonical correlation successfully clarified the complexity of simultaneous relationship of the relevant variables. These analyses are proved useful to demonstrate the relationship of cervico craniofacial skeletal and upper airway soft tissue morphology and selected demographic data. This lays down a basis for understanding the complicated pathogenic components of obese and nonobese OSA patients. PMID- 11211295 TI - Re: Handelman CS, Wang L, BeGole EA, Haas AJ. Nonsurgical rapid maxillary expansion in adults: report on 47 cases. Angle Orthod. 1999;70:129-144. PMID- 11211296 TI - Anterior space relations and lower incisor alignment in 9-year-old children born in the 1960s and 1980s. AB - The anterior arch spaces and the effect of early loss of deciduous canines have been studied in 2 different cohorts of 9-year-old children. One group of 119 children was from Norway and consisted of 56 girls and 63 boys, and 1 group of 133 children was from Sweden and consisted of 72 girls and 61 boys. Within these cohorts, half of the children were born in the 1960s and half in the 1980s. The 1960s group has been compared with the 1980s group to look for anterior arch changes occurring during this period of time. The children who had lost a lost deciduous canine at the age of 9 years were also compared with the children with all deciduous canines remaining. Groups were compared with analysis of variance. It was found that children with a lost deciduous canine at the age of 9 years belong to a group with less available arch space and are a crowded group when compared with an earlier study. For the girls, this was also associated with larger teeth. Anterior arch space did not differ between the 1960s and the 1980s groups except for the Swedish boys, where there was less available mandibular arch space in the 1980s group. The irregularity index for the 4 mandibular incisors was increased in the 1980s group compared with the 1960s group. This could indicate a secular trend toward an increased prevalence of malocclusion in the present population. PMID- 11211297 TI - Effective condylar growth and chin position changes in activator treatment: a cephalometric roentgenographic study. AB - Effective condylar growth (a summation of condylar remodeling, glenoid fossa remodeling, and condylar position changes within the fossa) and its influence on the position of the chin was analyzed in 40 class II, division I malocclusions treated successfully with activators. Additionally, the amount of mandibular rotation was assessed. Lateral head films in habitual occlusion from before and after an average treatment period of 2.6 years were evaluated. The Bolton Standards (32 untreated individuals with ideal occlusion) served as controls. Two different treatment effects were evaluated: overall growth change and treatment effects (overall growth changes minus age-related Bolton values). In comparison with the Bolton group, the activator patients exhibited an increase in the amount of vertical effective condylar growth (3.0 mm; P < .001), a decrease in the amount of sagittal effective condylar growth (0.6 mm; P < .05), and an increase in the amount of vertical development of the chin (1.8 mm; P < .001). No group differences could be found for sagittal development of the chin. In the Bolton group, the mandible rotated posteriorly, and in the activator group it rotated anteriorly (2.7 degrees; P < .001). The present investigation revealed that effective condylar growth can be increased and the chin position can be changed by activator treatment. Thus activator treatment induces skeletal changes, although not always in the desired (sagittal) therapeutic direction. PMID- 11211298 TI - Changes in circumferential neck measurements during movements of the head in children and their relevance to extraoral traction. AB - One of the causes of facebow injuries to patients wearing extraoral traction has been the catapult effect of the simple elasticized materials used in the past. A variety of safety or self-releasing modular systems to counteract this catapult effect are currently available. However, the strap extension provided by these modules varies considerably. To reduce the catapult effect to a minimum, it is desirable to fit a system with the minimal travel that will accommodate any changes in distance between the facebow and the back of the head or neck. To ascertain the minimal travel required for the straps, circumferential neck measurements were carried out on 105 children aged between 9 and 14 years. The change in circumference was recorded for 3 different head positions. The mean distance change between the back of the neck and the end of the facebow was 25 mm per side, with a range of 4 mm to 50 mm. This study suggests that on average, modules with a 25-mm extension will be required for cervical traction. PMID- 11211299 TI - The effect of growth hormone on craniofacial growth and dental maturation in Turner syndrome. AB - Serial cephalometric and panoramic radiographs from a mixed longitudinal group of 28 subjects with Turner syndrome (TS), age 4.4-19.0 years, were evaluated for annualized growth increments of the craniofacial complex and dental development and were compared with a longitudinal control group from the Burlington growth study. The short and retrognathic face characteristic of the syndrome was due largely to the increased cranial base angle, decreased posterior face height, and decreased mandibular length, all of which were significantly different from the controls. Although increases in statural height occurred in the TS children who were treated with human growth hormone (GH), there was little or no effect on growth of the jaws, particularly in the older subjects, and the characteristic facies of the syndrome persisted. Dental development was advanced in all TS subjects, and GH administration had no effect on the rate of dental development. PMID- 11211300 TI - The influences of molar intrusion on the inferior alveolar neurovascular bundle and root using the skeletal anchorage system in dogs. AB - The skeletal anchorage system (SAS) was developed as intraoral rigid anchors for open-bite correction by intrusion of molars. Since the application of SAS is a new modality in orthodontic treatment, the influences of radical molar intrusion on the root and the inferior alveolar neurovascular bundle were unknown. The purpose of this research is to verify the effect of molar intrusion on the neurovascular bundle, the level of osseointegration of bone screws, and root resorption. The results of this study showed mandibular molars were intruded 3.4 mm on the average over 7 months in dogs. The miniplates were well stabilized with osseointegrated bone screws and the peri-implant soft tissues showed slight inflammatory changes. Neither nerves nor blood vessels were damaged. Root resorption was observed but was repaired with new cementum. We concluded that the SAS utilizing transmucosal titanium miniplates as an immovable orthodontic anchorage could provide a new modality for molar intrusions without serious iatrogenic problems. PMID- 11211301 TI - Design and effectiveness of a computer-based continuing education program for orthodontists. AB - The design of computer-based continuing education for health professionals is an important consideration for Internet delivery because the size of graphic files greatly affects the speed with which information is delivered. Orthodontists who had indicated an interest in computer-based continuing education were shown via CD-ROM either a dynamic version of a computer continuing education program (with transitions and animations to liven up the content) or a plain version (identical content except that the transitions and animations were omitted). The program provided new information about superelastic arch wires for the initial stage of orthodontic treatment. For both versions, over 90% of the viewers thought the program was well done and provided useful information. Six of the orthodontists who received the dynamic version felt that the animations were distracting rather than helpful; only one who received the plain version felt that it was lifeless. A follow-up questionnaire showed that two-thirds of those who viewed the program had subsequently reviewed the performance data for the initial wire they were using and 20% had changed it, so the computer program was effective in changing clinical behavior. Those who saw the plain version also were more likely to have changed their clinical procedures. For Internet delivery of information to highly motivated professionals, it appears that transitions and animations are not necessary and may be more likely to decrease than increase the effectiveness of the teaching material. PMID- 11211302 TI - What do they want, anyway? PMID- 11211303 TI - Intranet-based quality improvement documentation at the Veterans Affairs Maryland Health Care System. AB - The Pathology and Laboratory Medicine Service of the Veterans Affairs Maryland Health Care System is inspected biannually by the College of American Pathologists (CAP). As of the year 2000, all documentation in the Anatomic Pathology Section is available to all staff through the VA Intranet. Signed, supporting paper documents are on file in the office of the department chair. For the year 2000 CAP inspection, inspectors conducted their document review by use of these Web-based documents, in which each CAP question had a hyperlink to the corresponding section of the procedure manual. Thus inspectors were able to locate the documents relevant to each question quickly and efficiently. The procedure manuals consist of 87 procedures for surgical pathology, 52 procedures for cytopathology, and 25 procedures for autopsy pathology. Each CAP question requiring documentation had from one to three hyperlinks to the corresponding section of the procedure manual. Intranet documentation allows for easier sharing among decentralized institutions and for centralized updates of the laboratory documentation. These documents can be upgraded to allow for multimedia presentations, including text search for key words, hyperlinks to other documents, and images, audio, and video. Use of Web-based documents can improve the efficiency of the inspection process. PMID- 11211304 TI - Primary cutaneous T-cell-rich B-cell lymphoma: clinically distinct from its nodal counterpart? AB - The cases of two patients with Stage IE primary cutaneous T-cell-rich B-cell lymphoma (TCRBCL) are described. In both, the lesion showed a dense infiltrate by numerous small T lymphocytes with scattered histiocytes and large atypical B lymphoid cells. Polymerase chain reaction assays demonstrated that the B cells were monoclonal, with immunoglobulin heavy-chain gene rearrangement. No clonal rearrangements of the T-cell receptor gamma gene were observed. Both patients were disease-free at 4 months and at 5 years after therapy, respectively. Although rare, primary cutaneous T-cell-rich B-cell lymphoma appears to have a better prognosis than its nodal counterpart, with or without skin involvement. PMID- 11211305 TI - Fetal brain to liver weight ratio as a measure of intrauterine growth retardation: analysis of 182 stillborn autopsies. AB - The fetal brain/liver weight ratio of 182 stillborn fetuses was analyzed for its value as a measure of intrauterine growth retardation. The ratio was evaluated as a test for the detection of small-for-gestational age fetuses, compared with the ponderal index, and evaluated for correlation with maternal histories that were compatible with fetal growth retardation. Both brain/liver ratio and ponderal index were insensitive and relatively nonspecific indicators of low fetal body weight in this population. Brain/liver weight ratio was considerably more sensitive in those cases that were at least 20 weeks of gestational age, and specificity increased as the cut-off point was increased above 3. Those cases with maternal history or placental findings compatible with asymmetrical-type intrauterine growth retardation were statistically more likely to have elevated brain/liver weight ratios and depressed ponderal indices, but there was considerable overlap among cases with different disease types. Prosectors of fetal autopsies must make use of all the information available to them. The fetal brain/liver weight ratio and the ponderal index may be useful, but they are not satisfactory indicators of intrauterine growth retardation by themselves, and they also may be inadequate for the detection of growth retardation etiology. PMID- 11211306 TI - Reversible transdifferentiation: interconversion of somatotrophs and lactotrophs in pituitary hyperplasia. AB - Previous studies conclusively demonstrated transformation of somatotrophs into bihormonal mammosomatotrophs in gestational lactotroph hyperplasia during pregnancy. Similar transdifferentiation of somatotrophs into thyrotrophs through bihormonal intermediate thryrosomatotrophs was documented during thyrotroph hyperplasia in both rodent and human pituitaries in hypothyroidism. The cessation of the stimulation resulted in reversal of the process in both conditions. The conversion of lactotrophs into somatotrophs was suggested but not documented previously in the human gland. The present study was undertaken to investigate cases of somatotroph hyperplasia by transmission electron microscopy, immunoelectron microscopy using double immunogold labeling for growth hormone and prolactin, as well as combined immunocytochemistry and in situ hybridization. Adenohypophysial tissue was removed from a 38-year-old man and a 29-year-old woman with long-standing acromegaly due to ectopic overproduction of growth hormone-releasing hormone (GRH) by bronchial carcinoid tumors. For comparison, two pituitary biopsies were studied: one from a 38-year old woman with idiopathic lactotroph hyperplasia and one from a 14-year-old boy with secondary lactotroph hyperplasia due to a suprasellar craniopharyngioma. In the patients with somatotroph hyperplasia, the prevailing cell type was the hyperplastic somatotroph joined by mammosomatotroph deriving from lactotrophs, whereas monohormonal lactotrophs were rare. The predominance of mammosomatotrophs and active lactotrophs was documented in the patient with idiopathic lactotroph hyperplasia, whereas the case of the patient with secondary lactotroph hyperplasia was characterized by monohormonal lactotrophs and somatotrophs, but mammosomatotrophs were rare. That finding in the pituitary of the boy suggests that participation of mammosomatotrophs in lactotroph hyperplasia is not unconditional Our findings conclusively demonstrate conversion of lactotrophs into mammosomatotrophs during somatotroph hyperplasia, providing further evidence for the potential of reversible transdifferentiation between somatotrophs and lactotrophs in response to functional demand. PMID- 11211307 TI - Altered distribution of beta-catenin, and its binding proteins E-cadherin and APC, in ulcerative colitis-related colorectal cancers. AB - The beta-catenin pathway plays a central role in transcriptional signaling and cell-cell interactions in colonic epithelium. Alterations of the expression of beta-catenin, and its binding partners E-cadherin and the adenomatous polyposis coli protein (APC), are frequent events in sporadic colorectal cancer. Ulcerative colitis (UC)-related cancers originate in a field of chronic inflammation and therefore may have different alterations in the beta-catenin pathway than sporadic cancers. To test this hypothesis, expression and subcellular localization of beta-catenin, E-cadherin, and APC were detected by immunohistochemistry in paraffin sections from 33 UC-related and 42 sporadic colorectal cancers. Although beta-catenin and E-cadherin expression were predominantly limited to the lateral cell membrane in normal colonic epithelium, both tumor groups showed an overall shift from membranous to cytoplasmic expression for these proteins. An increase in nuclear localization of beta catenin and a decrease in cytoplasmic APC expression also were seen in both cancer groups compared with normal epithelium. Abnormal beta-catenin expression was more closely linked to E-cadherin alterations in UC-related cancers than in sporadic cancers. In contrast, abnormal beta-catenin expression was more closely linked to APC alterations in sporadic cancers than in UC-related cancers. These data suggest that alterations of the beta-catenin pathway are important in both UC-related and sporadic colorectal cancers. However, differences in the expression patterns of beta-catenin, E-cadherin, and APC between UC-related and sporadic colorectal cancers suggest that the specific alterations in this pathway may differ in these two cancer groups. PMID- 11211310 TI - Effects of bisphosphonate on the release of MMP-2 from cultured human osteoblasts. AB - Production of matrix metalloproteinases (MMPs) influences bone resorption. We investigated the role of bisphosphonates, potent inhibitors of bone resorption, on the production of MMP-2 from human osteoblasts. Bisphosphonates alone did not influence the amount of MMP-2 produced by human osteoblasts. However, in the presence of physiological concentrations of plasmin, bisphosphonates reduced the amount of MMP-2 in osteoblasts-conditioned media. Furthermore, bisphosphonates treatment induced degradation of MMP-2 in the presence of plasmin. Our results indicated that bisphosphonate, a divalent cation chelator, negatively regulated the longevity of MMP-2 in soluble phase plasmin-containing environment. These findings suggest that bisphosphonates inhibit bone resorption by abrogating MMP-2 protection induced by plasmin-mediated degradation. PMID- 11211308 TI - Human small cell lung carcinoma and carcinoid tumor regulate dendritic cell maturation and function. AB - The induction of apoptosis in dendritic cells (DC) is a key mechanism by which tumors escape immune recognition and elimination. In fact, a number of studies have showed the correlation between the number of DC within the tumor and the clinical prognosis, suggesting that increased infiltration of tumor tissue by DC was associated with better patient survival and low incidence of metastatic disease. We compared the number of DC and their distribution pattern in human small-cell lung carcinoma and bronchial carcinoid tumor (CT) tissues. Immunohistochemical analysis revealed the presence of cells expressing DC markers CD1a and CD83 in small-cell lung carcinoma tissues and the complete absence of these cells in CT samples. Next, we examined whether human lung tumor cells produce soluble factors that inhibit differentiation of hematopoietic precursors into mature DC. The addition of small-cell lung carcinoma-conditioned medium to CD34+ precursor cell cultures significantly inhibited colony-forming units of DC formation when compared with nontreated control DC cultures. Furthermore, DC generation and differentiation was completely abrogated in CD34+ cell cultures treated with CT-conditioned medium, suggesting that CT-derived factors blocked CD34+ cell differentiation into DC or induced their apoptosis. Finally, flow cytometry analysis of cultured DC confirmed these results. Thus, analysis of our data suggests that human lung tumors produce factors that inhibit DC generation or maturation and may also induce apoptotic death of DC precursors in vitro. PMID- 11211309 TI - Clear cell sarcoma shows immunoreactivity for microphthalmia transcription factor: further evidence for melanocytic differentiation. AB - Microphthalmia transcription factor, a melanocytic nuclear protein critical for the embryonic development and postnatal viability of melanocytes, is a master regulator in modulating extracellular signals. Recently, microphthalmia transcription factor expression was shown to be both a sensitive and specific marker of epithelioid melanoma. We investigated the sensitivity of D5, an anti microphthalmia transcription factor antibody, for diagnosis of clear cell sarcoma (also known as malignant melanoma of soft parts). Immunoreactivity in a nuclear pattern for D5 was present in 8 of 12 (75%) tumors. D5 staining was strong in three tumors, moderate in two, and weak in three. S-100 protein expression was seen in all 12 cases that had clear cell sarcoma examined. HMB-45 staining was seen in 11 of 12 (92%) tumors. Focal Melan-A positivity was seen in 3 of 7 (43%) tumors. Although D5 was shown in a previous study to be a highly sensitive and specific marker for epithelioid melanomas, the results of this study expand the spectrum of tumors showing immunoreactivity for D5. D5 immunoreactivity in clear cell sarcoma provides further evidence for melanocytic differentiation in this unusual tumor. PMID- 11211311 TI - Wing-shaped end-to-end anastomosis for the treatment of high jejunal atresia. AB - Six infants with jejunal atresia, one infant with ileal atresia, and one infant with colonic atresia were managed by a newly developed wing-shaped end-to-end anastomosis. The technique was accomplished by anastomosing the tip of the dilated proximal bowel to the diminutive distal bowel, which had been divided into two parts, including the mesentery. The completed anastomosis resembled extended wings, and this technique was therefore named wing-shaped anastomosis. This technique for anastomosis is effective in preventing functional obstruction because no axial deviation between the proximal and distal anastomotic bowels exists, and the mucosal absorptive surface is completely preserved. PMID- 11211312 TI - Interferon-gamma stimulates the expression of CX3CL1/fractalkine in cultured human endothelial cells. AB - CX3CL1/Fractalkine, a CX3C chemokine, is a potent agonist for the chemotaxis and adhesion of monocytes and lymphocytes. It was first identified as a membrane protein in endothelial cells activated with IL-1 or TNF-alpha. We have found the enhanced expression of fractalkine in human umbilical vein endothelial cells stimulated with interferon-gamma (IFN-gamma). Pretreatment of the cells with cycloheximide did not inhibit the expression of fractalkine mRNA. The majority of fractalkine protein was found in the cell lysate, and an antibody-blocking experiment disclosed that fractalkine contributes to the adhesion of mononuclear cells to endothelial monolayers stimulated with IFN-gamma. Vascular endothelial cells produce fractalkine in response to IFN-gamma, and this may play an important role in immune responses by eliciting a traffic of mononuclear cells through the vascular wall. PMID- 11211313 TI - Herpesvirus alkaline deoxyribonuclease; a possible candidate as a novel target for anti-herpesvirus therapy. AB - Herpesvirus alkaline deoxyribonucrease (DNase) is coded in the genome of all herpesvirus species determined total sequence and is conserved in structure. In order to determine whether the enzyme could be a target for a novel antiherpesvirus therapy, the anti-herpes simplex virus type 1 (HSV-1) activity of antisense oligonucleotide for HSV-1 alkaline DNase was studied. Six antisense phosphorothioate oligonucleotides, targeted to an internal AUG start codon, were designed and evaluated. One of the oligonucleotides, UL12-4, inhibited wild type and thymidine kinase-deficient HSV-1 replication to 21.5 and 19.5% at 40 microM, respectively. The quantity of alkaline DNase mRNA and DNase activity in HSV-1 infected Vero cells was reduced to one eighth and 66.9% of control, respectively, by treatment with 40 microM of UL12-4, but no effect was observed on the quantity of HSV-1 glycoprotein H mRNA (gamma2 gene) or on the replication of Vero cells. These results indicate that UL12-4 inhibits HSV-1 replication by decreasing the amount of alkaline DNase mRNA. The herpesvirus alkaline DNase could be a novel target for anti-herpesvirus drug. PMID- 11211314 TI - Acute disseminated encephalomyelitis developed after acute herpetic gingivostomatitis. AB - A child with acute disseminated encephalomyelitis (ADEM) developed after acute herpetic gingivostomatisis was described. Inspite of the improvement of his gingivostomatitis, his consciousness gradually deteriorated and he was admitted to Nakadori General Hospital. His consciousness level was drowsiness and increased bilateral patellar reflexes were shown. Because magnetic resonance imaging (MRI) T2-weighted scan showed areas of high signal intensity disseminated in superior portion of medulla oblongata, dorsal portion of pons, basal nuclei and thalamus, he was suspected as having ADEM. Anti-herpes simplex virus (HSV) 1 IgG and IgM antibodies elevated in both blood and cerebrospinal fluid. From these results, HSV1 infection was thought to be the preceding infection of ADEM. Methylprednisolone therapy (20 mg/kg daily) for 3 days, followed by prednisolone (2 mg/kg) was started, with an excellent response. In addition, administration of acyclovir was also continued, considering the complication of HSV encephalitis. MRI T2-weighted scan performed at 2 months later after the onset of ADEM revealed disappearance of the lesions. He was discharged without remaining disorders. It is difficult to distinguish between ADEM and HSV encephalitis because both of these diseases show various neurological symptoms. In our case, MRI was the most useful method for correct diagnosis of ADEM. We concluded that ADEM is important as a disease of central nervus system due to HSV1 infection, in addition to encephalitis. PMID- 11211315 TI - Focal segmental glomerulosclerosis: unremitting proteinuria of long duration as a possible etiology? AB - A Japanese boy aged 9 years referred to our hospital because of steroid-resistant proteinuria. He had a 6-year history of unremitting proteinuria and was diagnosed as having minimal-change disease (MCD) by the repeated renal biopsies performed at the age of 3.5 years and 8.5 years, respectively. His proteinuria fluctuated ranging from 115 mg/100 ml to 645 mg/100 ml, and serum total protein ranged from 59 g/liter to 63 g/liter. The third renal biopsy at the presentation also revealed MCD. Thereafter he was treated with an anti-thrombocyte agent combined with an angiotensin converting enzyme inhibitor. Despite unremitting proteinuria of long duration, he did not have any complaints. At the age of 11.5 years, severe tubulointerstitial lesion was observed in the fourth renal biopsy. The fifth renal biopsy 6 months after the fourth finally revealed the lesion of focal segmental glomerulosclerosis (FSGS). Although the interpretation of his repeated renal biopsies were considered to be limited, these clinical observation suggested that his unremitting proteinuria of long duration might have been attributed to subsequent progression FSGS. PMID- 11211316 TI - Secondary infections of AIDS autopsy cases in Japan with special emphasis on Mycobacterium avium-intracellulare complex infection. AB - In order to study the frequency of secondary infections of AIDS autopsy cases in Japan, especially the frequency of Mycobacterium aviumintracellulare complex (MAC) infection, retrospective autopsy study was conducted between 1986 and 1997 at the affiliated hospital of Institute of Medical Sciences, University of Tokyo. Secondary infections of various organs from 43 AIDS autopsy cases were examined using histopathology, genetic diagnosis of tuberculosis, Ziehl-Neelsen stain for acid-fast bacilli and immunohistochemistry. Nontuberculous mycobacterial infection (Mycobacterium avium) was observed in 17 cases (40%) out of 43 using polymerase chain reaction (PCR), but M. tuberculosis infection was not observed. Ziehl-Neelsen staining showed a positive reaction in lung and spleen tissues of 7 AIDS autopsy cases. Immunohistochemistry using anti-BCG antibody revealed positivity in 7 AIDS autopsy cases. CD4 counts of 17 AIDS patients with mycobacterial infection were less than 18.7/microl. Other opportunistic infections were also examined by histopathology. Secondary infections were present in every case, and these included cytomegalovirus infection (32 cases), Pneumocystis carinii (15 cases), Candida (16 cases), Aspergillus (12 cases), Cryptococcus (6 cases), Toxoplasma (6 cases), methicillin-resistant Staphylococcus aureus (3 cases), herpes virus (1 case) and Entamoeba histolytica (1 case). Malignant lymphoma was recognized in 14 cases and Kaposi's sarcoma in 6. This is the systemic report on secondary infections of AIDS autopsy cases in Japan. In diagnosis of mycobacterial infections, PCR was more useful than staining for acid-fast bacilli and immunohistochemistry. Secondary infections (especially mycobacterial infection) were closely associated with the low CD4 count. PMID- 11211317 TI - The new look of premises liability. PMID- 11211318 TI - Paying the piper: the crisis in chronic care. AB - The current article reviews the broad outlines of the crisis in chronic care with emphasis on Southern California, a region where the powerful forces buffeting health and long term care have reached gale force intensity. The article argues that a partial solution to the crisis lies in flexible local partnerships among patients, families, providers, and payers focused on helping the chronically ill cope with the tasks of daily life. Such partnerships would emphasize supportive care, prevention, family preservation, assistive devices, and family income supplementation through facilitation of productive work, aspects of chronic care neglected by current financing and service delivery practices. A case example, the Southern California-based Partners in Care Foundation's Family Care Network, illustrates these essential components of a revitalized, responsive chronic care system. PMID- 11211319 TI - Typology of quality of life experiences among persons living with HIV. AB - This article develops a typology of 2,038 participants in 13 innovative HIV/AIDS treatment model service demonstration projects targeted to traditionally underserved populations. The typology is based on self-reported health-related quality of life levels. Eight clusters were identified that classify HIV/AIDS patients based on their reported health-related quality of life. Participants were clustered based on their overall levels of quality of life, as well as by deficits in specific areas of functioning such as energy level, physical impairment, and role impairment. However, factor analysis suggests that health related quality of life as perceived by the HIV-positive participants is best represented as a single underlying dimension and an ordering of the types shows that they are consistently related, in the same order, to several criterion measures of impairment. The results suggest that a general categorization of patients with HIV in terms of quality of life is more meaningful than an assessment of the relative areas of impairment. Since the impairment ratings were also self-reported, analyses relating quality of life clusters to actual symptom levels and healthcare utilization are needed. Implications for the assessment of health-related quality of life and the evaluation of service delivery programs for persons living with HIV are discussed. PMID- 11211321 TI - Use of adult day services and home health care services by older adults: a comparative analysis. AB - This study compares adult day services (ADS) and home health care (HHC) users on the indicators of personal characteristics, physical health, mental health and social network contacts. Analysis includes all 62 reported ADS users and a random sample of 91 HHC users from the Longitudinal Study of Aging. Results indicate that ADS users are younger, have greater cognitive impairment, need more supervisory assistance with activities of daily living (ADLs), and have more social contacts than HHC users. The findings also underscore the importance of emphasizing the functional and cognitive limitations in differentiating home- and community-based services. Instead of exclusively focusing on physical needs, authors suggest strategies that ensure integrated care models to address physical, mental and social needs of elders in both settings. PMID- 11211320 TI - Service needs and factors related to quality of life at time of service enrollment among persons living with HIV. AB - This article explores the relationships of HIV risk factors, service needs, and vulnerabilities to health-related quality of life in a sample of 1,371 participants newly enrolled into 13 innovative HIV/AIDS treatment model service demonstration projects. These projects targeted services to traditionally underserved populations. Eight distinct quality of life clusters of HIV patients were used in this analysis along with patient self-identified risk factors. The quality of life clusters were based on patient self-reported quality of life dimensions. The eight clusters were differentiated based on relative strengths and weaknesses in physical functioning, energy levels, and social functioning. Data on patient need-vulnerability factors and demographic characteristics were related to these eight clusters using the data modeling method of Exhaustive CHAID (Chi-squared Automatic Interaction Detector). Through this method, the characteristics most likely to be associated with higher and lower levels of quality of life at the time of enrollment into services were identified. The results provide further support that quality of life assessment is a useful clinical tool for monitoring patient progress. PMID- 11211323 TI - Clinton's regulations may be model for patient-rights legislative push. PMID- 11211322 TI - Case management decision making: goal transformation through discretion and client interpretation. AB - This study examines the decision-making strategies employed by case managers in a state-funded home care program for the elderly. Specifically, this study applies Lipsky's (1980) theory of street-level bureaucracy to gerontological research on case management decision making in an effort to demonstrate the presence of case management discretion, and the impact of that discretion on home care implementation. Drawing upon individual interviews and focus group interviews, results suggest the applicability of the proposed framework, and indicate the need for policy planners to identify factors for case manager discretion that result in undesirable home care goal transformation. PMID- 11211324 TI - Ohio struggles to rescue managed Medicaid program. PMID- 11211325 TI - 'Blueprint for the future' may lessen HMOs' impact. Interview by Frank Diamond. PMID- 11211326 TI - Compensation monitor. When pressure's on, raises get better. PMID- 11211327 TI - How medical managers avoid mindsets that are minefields. PMID- 11211328 TI - Florida leads the way in attempting disease management for Medicaid. PMID- 11211329 TI - An opportunity for HMOs to use marketing to increase enrollee satisfaction. AB - PURPOSE: To identify the combination of marketing components (i.e., service, price, access, and promotion) of commercial health maintenance organizations (HMOs) that are related to overall enrollee satisfaction. The researchers focus on factors that commercial HMOs control directly--specifically, health care organization and financing. DESIGN: Descriptive (mail order). METHODOLOGY: This study uses national data provided by a major health benefits consulting firm, which collected data from a 1997 calendar year mail survey of HMO administrators. The administrators responded to an extensive survey, which tapped selected HMO marketing-mix components and the percentage of surveyed members who indicated satisfaction with their HMOs. To test hypotheses, researchers treated marketing mix components as independent variables and enrollee satisfaction as the dependent variable. PRINCIPAL FINDINGS: This study found statistically significant relationships between overall satisfaction and HMO providers' quality; access, particularly to specialists and out-of-network providers; waiting times for physician services; customer service; and disease prevention/health promotion programs. The researchers did not find significant relationships between overall satisfaction and accreditation by the National Committee for Quality Assurance (NCQA), the presence of physician gatekeepers, numbers of providers, or financial indicators. The relationship between overall satisfaction and utilization was mixed. This study's findings are largely consistent with the literature, consumer- and professional-group position papers, and the President's Advisory Commission on Consumer Protection and Quality in the Health Care Industry. CONCLUSIONS: HMOs can use marketing as a way to address problems and pursue opportunities identified by enrollees. As these findings demonstrate, certain features of HMO design are more appealing to patients. By focusing on these preferences, HMOs can adopt a responsive market orientation that gives rise to more effective marketing mixes and hence improves enrollee satisfaction. With improved satisfaction, enrollees generate less need for government intervention through regulation or legislation. PMID- 11211330 TI - When claims are audited, following compliance laws matters. PMID- 11211331 TI - There once was a man who could not feel disgust. PMID- 11211332 TI - Managed care outlook. HMO members willing to pay to manage benefits online. PMID- 11211333 TI - A woman's right to stay. New rules would offer asylum to battered women. PMID- 11211334 TI - Where we come from. Recent advances in genetics are starting to illuminate the wanderings of early humans. PMID- 11211335 TI - Rustling up a plan. Can the U.S. prevent a mad cow medical crisis? PMID- 11211336 TI - Improved AIDS treatments bring life and hope--at a cost. PMID- 11211337 TI - Medical privacy rules give patients and marketers access to health data. PMID- 11211338 TI - Pregnant women get no bologna--or shark or brie. PMID- 11211339 TI - [History of the Geneva Society of Mental Health Promotion, 1906-2000]. PMID- 11211340 TI - [Feminization of the medical profession and the division of labor between men and women: masculine hunting grounds and feminine niches]. PMID- 11211341 TI - [Cultural and social pluralism, what implications for the practice of medicine?]. PMID- 11211343 TI - [Introduction: medicine, history, society]. PMID- 11211344 TI - [The patient and his entourage in the XVIIIth century: mediations in the correspondence consultations of Dr. Tissot]. PMID- 11211345 TI - [Variola and goiter: two public health conceptions]. PMID- 11211346 TI - [Birth and evolution of legal psychiatry in Switzerland, 1890-1950]. PMID- 11211347 TI - [Sterilization of sick and mentally handicapped patients in the Fribourg and Geneva cantons in the XXth century]. PMID- 11211348 TI - [Abortion practice in Geneva in thirty years]. PMID- 11211349 TI - [Physicians and sex education in the school milieu in the canton of Vaud]. PMID- 11211350 TI - [The birth of "painless childbirth"]. PMID- 11211351 TI - [How instruments better the world: the electron microscope between science and medicine in Geneva (1945-1970)]. PMID- 11211352 TI - Service learning in the undergraduate health administration curriculum: theory and practice. AB - Changing the focus of the health care system from individual to population-based health presents challenges for health administration programs as they search for innovative ways to educate students who can work in interdisciplinary and diverse environments. The increased utilization of service learning in health profession schools suggests that service learning is a way to contribute to student learning, social awareness and the health of community. Undergraduate health administration programs can take on the same challenge by integrating service learning into their curriculum. This study introduces the service learning concept into the health administration curriculum, demonstrates service learning models and recommends several health administration courses for service learning integration. PMID- 11211353 TI - The role of gender in MPH graduates' salaries. AB - Several studies have demonstrated that workforce roles and salaries differ substantially between men and women in administrative positions within the health care industry. Recent studies of graduates with masters of business administration (MBA) and masters of health administration (MHA) degrees have indicated that women tend to experience lower salaries, given like responsibilities. However, the impact of gender on salary has been less studied among masters of public health (MPH) graduates in the health care field. Our objective was to assess the impact of gender on salary among MPH degree graduates. Using a cross-sectional survey of all graduates from the MPH program at Yale University between 1991-1997 (n = 201, response rate = 51%), we ascertained graduates' reported salary in the first job post-graduation and reported salary in their current position. Bivariate and multivariate analyses were used to assess the unadjusted and adjusted associations between gender and salary. Salaries in both the first job post-graduation and in the current job differed significantly by gender, with women earning less than men (p-values < .05). Moreover, these differences persisted after controlling for a set of human capital measures including pre-MPH work experience, age at graduation, years since graduation, area of specialization within the MPH degree, and type of work site (governmental or nonprofit versus for-profit). Unlike studies of MBA and MHA graduates, however, this study did not find evidence that the gender-related salary gap widened as the years since graduation increased, although the sample size did not allow comprehensive testing of this trend. PMID- 11211354 TI - Gender differences in the early careers of health care managers. AB - In health care, as in many other fields, women's occupational advancement appears to occur more slowly than men's. Two main theories purport to explain this phenomenon: 1) the "glass ceiling" perspective which focuses on structural arrangements and/or the attitudes of those who make promotion decisions, and 2) "supply side" approaches which argue that characteristics of women themselves explain their relative lack of progress. There is also another view that challenges the glass ceiling, suggesting that it affects predominantly older cohorts of women, and that younger entrants experience few advancement obstacles. This study examines these questions using a population of health administrators who graduated between May, 1984 and May, 1995. Gender comparisons reveal considerable similarity between men and women graduates on a variety of early career outcome variables, disputing supply side arguments and suggesting that barriers to women, if they exist, become important after the early career period. PMID- 11211355 TI - Interprofessional learning modules at Dalhousie University. AB - Interprofessional education has been advocated to improve teamwork in the health sector. This paper reports on the first two years of operational experience by a School of Health Services Administration (SHSA) with three-hour interprofessional learning modules (IPLMs). SHSA students participated along with students from nursing, medicine, social work, physiotherapy, occupational therapy, pharmacy, speech language pathology, audiology, dental hygiene, dentistry, leisure studies, health education and kinesiology. The five IPLMs required for SHSA students were: professional roles and values, integrity in scholarly activity, disability, interpersonal violence and HIV/AIDS. This article describes the development, delivery and evaluation of these modules from an SHSA perspective. The IPLMs' evaluation findings indicated that IPLMs are worthwhile, but have taken years and ongoing senior management support to operationalize; inclusion of health services administration is worthwhile but challenging; vigilance is needed to retain an IP rather than module content focus; and faculty and facilitator development, along with student preparation and debriefing, is required. Student feedback was favourable; faculty members have gained by their involvement; and field practitioner support has been sustained. Evaluation and reflection are critical to IPLM evolution. The norms, strengths and constraints of the university must be taken into account, and thus IPLMs must be adapted for each educational setting. Schools of health services administration must decide whether they wish to be involved in interprofessional learning. PMID- 11211356 TI - Teaching information management. AB - Managing in the present chaotic hospital financing environment requires integrated clinical/financial data systems and people who know how to use them. Health care management students of the present and future will need to understand how these information systems are structured and used. This article describes a graduate course in integrated clinical/financial information management as it has evolved at Yale University. The course provides students a vicarious experience in information management through class sessions and exercises using a database of real patient and cost center level information. Health care management of the future will depend on interdisciplinary collaboration and partnerships in education between provider organizations and academic programs. Both are modeled in the course. PMID- 11211357 TI - International health services management education: an overview of major efforts and lessons learned during the 1990s. AB - In this paper, the authors examine select major pedagogical and methodological issues concerning health care management executive training and academic program development in the former Soviet sphere of influence during the 1990s. Experience from programs offered during the 1990s has direct implications for the continued development of health care management programs and faculty in the United States. In essence, each of the nations that were involved represented an experimental setting for the introduction and improvement of management skills in the health care sector and the development of professional health care managers. Evaluative findings should help to inform future efforts to construct and deliver effective international and domestic management educational programs. PMID- 11211358 TI - Therapy for anorexia nervosa. PMID- 11211359 TI - More on the DICA-IV. PMID- 11211360 TI - Reactive attachment disorder. PMID- 11211361 TI - Olanzapine and hypertriglyceridemia. PMID- 11211362 TI - Introduction--ADHD comorbidity and treatment outcomes in the MTA. PMID- 11211363 TI - ADHD comorbidity findings from the MTA study: comparing comorbid subgroups. AB - OBJECTIVES: Previous research has been inconclusive whether attention deficit/hyperactivity disorder (ADHD), when comorbid with disruptive disorders (oppositional defiant disorder [ODD] or conduct disorder [CD]), with the internalizing disorders (anxiety and/or depression), or with both, should constitute separate clinical entities. Determination of the clinical significance of potential ADHD + internalizing disorder or ADHD + ODD/CD syndromes could yield better diagnostic decision-making, treatment planning, and treatment outcomes. METHOD: Drawing upon cross-sectional and longitudinal information from 579 children (aged 7-9.9 years) with ADHD participating in the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention Deficit/Hyperactivity Disorder (MTA), investigators applied validational criteria to compare ADHD subjects with and without comorbid internalizing disorders and ODD/CD. RESULTS: Substantial evidence of main effects of internalizing and externalizing comorbid disorders was found. Moderate evidence of interactions of parent-reported anxiety and ODD/CD status were noted on response to treatment, indicating that children with ADHD and anxiety disorders (but no ODD/CD) were likely to respond equally well to the MTA behavioral and medication treatments. Children with ADHD-only or ADHD with ODD/CD (but without anxiety disorders) responded best to MTA medication treatments (with or without behavioral treatments), while children with multiple comorbid disorders (anxiety and ODD/CD) responded optimally to combined (medication and behavioral) treatments. CONCLUSIONS: Findings indicate that three clinical profiles, ADHD co-occurring with internalizing disorders (principally parent-reported anxiety disorders) absent any concurrent disruptive disorder (ADHD + ANX), ADHD co-occurring with ODD/CD but no anxiety (ADHD + ODD/CD), and ADHD with both anxiety and ODD/CD (ADHD + ANX + ODD/CD) may be sufficiently distinct to warrant classification as ADHD subtypes different from "pure" ADHD with neither comorbidity. Future clinical, etiological, and genetics research should explore the merits of these three ADHD classification options. PMID- 11211364 TI - Multimodal treatment of ADHD in the MTA: an alternative outcome analysis. AB - OBJECTIVE: To conduct a post hoc investigation of the utility of a single composite measure of treatment outcome for the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA) at 14 months postbaseline. BACKGROUND: Examination of multiple measures one at a time in the main MTA intent-to-treat outcome analyses failed to detect a statistically significant advantage of combined treatment (Comb) over medication management (MedMgt). A measure that increases power and precision using a single outcome score may be a useful alternative to multiple outcome measures. METHOD: Factor analysis of baseline scores yielded two "source factors" (parent and teacher) and one "instrument factor" (parent-child interactions). A composite score was created from the average of standardized parent and teacher measures. RESULTS: The composite was internally consistent (alpha = .83), reliable (test-retest over 3 months = 0.86), and correlated 0.61 with clinician global judgments. In an intent-to-treat analysis, Comb was statistically significantly better than all other treatments, with effect sizes ranging from small (0.28) versus MedMgt, to moderately large (0.70) versus a community comparison group. CONCLUSIONS: A composite of ADHD variables may be an important tool in future treatment trials with ADHD and may avoid some of the statistical limitations of multiple measures. PMID- 11211365 TI - Clinical relevance of the primary findings of the MTA: success rates based on severity of ADHD and ODD symptoms at the end of treatment. AB - OBJECTIVES: To develop a categorical outcome measure related to clinical decisions and to perform secondary analyses to supplement the primary analyses of the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA). METHOD: End-of-treatment status was summarized by averaging the parent and teacher ratings of attention deficit/hyperactivity disorder and oppositional defiant disorder symptoms on the Swanson, Nolan, and Pelham, version IV (SNAP-IV) scale, and low symptom-severity ("Just a Little") on this continuous measure was set as a clinical cutoff to form a categorical outcome measure reflecting successful treatment. Three orthogonal comparisons of the treatment groups (combined treatment [Comb], medication management [MedMgt], behavioral treatment [Beh], and community comparison [CC]) evaluated hypotheses about the MTA medication algorithm ("Comb + MedMgt versus Beh + CC"), multimodality superiority ("Comb versus MedMgt"), and psychosocial substitution ("Beh versus CC"). RESULTS: The summary of SNAP-IV ratings across sources and domains increased the precision of measurement by 30%. The secondary analyses of group differences in success rates (Comb = 68%; MedMgt = 56%; Beh = 34%; CC = 25%) confirmed the large effect of the MTA medication algorithm and a smaller effect of multimodality superiority, which was now statistically significant (p < .05). The psychosocial substitution effect remained negligible and nonsignificant. CONCLUSION: These secondary analyses confirm the primary findings and clarify clinical decisions about the choice between multimodal and unimodal treatment with medication. PMID- 11211366 TI - Impairment and deportment responses to different methylphenidate doses in children with ADHD: the MTA titration trial. AB - OBJECTIVE: Results of the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA) were analyzed to determine whether a double-blind, placebo-controlled methylphenidate (MPH) titration trial identified the best MPH dose for each child with attention deficit/hyperactivity disorder (ADHD). METHOD: Children with ADHD assigned to MTA medication treatment groups (n = 289) underwent a controlled 28-day titration protocol that administered different MPH doses (placebo, low, middle, and high) on successive days. RESULTS: A repeated-measures analysis of variance revealed main effects for MPH dose with greater effects on teacher ratings of impairment and deportment (F3 = 100.6, n = 223, p = .0001; effect sizes 0.8-1.3) than on parent ratings of similar endpoints (F3 = 55.61, n = 253, p = .00001; effect sizes 0.4-0.6). Dose did not interact with period, dose order, comorbid diagnosis, site, or treatment group. CONCLUSIONS: The MTA titration protocol validated the efficacy of weekend MPH dosing and established a total daily dose limit of 35 mg of MPH for children weighing less than 25 kg. It replicated previously reported MPH response rates (77%), distribution of best doses (10-50 mg/day) across subjects, effect sizes on impairment and deportment, as well as dose-related adverse events. PMID- 11211367 TI - Methylphenidate dosage for children with ADHD over time under controlled conditions: lessons from the MTA. AB - OBJECTIVES: To examine the trajectory of methylphenidate (MPH) dosage over time, following a controlled titration, and to ascertain how accurately the titration was able to predict effective long-term treatment in children with attention deficit/hyperactivity disorder (ADHD). METHOD: Using the 14-month-treatment database of the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA), the outcome of the initial placebo-controlled, double-blind, randomized daily switch titration of MPH was compared with the subsequent maintenance pharmacotherapy. Children received monthly monitoring visits and, when needed, medication adjustments. RESULTS: Of the 198 children for whom MPH was the optimal treatment at titration (mean +/- SD dose: 30.5 +/- 14.2 mg/day), 88% were still taking MPH at the end of maintenance (mean dose 34.4 +/- 13.3 mg/day). Titration-determined dose and end of-maintenance dose were significantly correlated (r = 0.52-0.68). Children receiving combined pharmacotherapy and behavioral treatment ended maintenance on a lower dose (31.1 +/- 11.7 mg/day) than did children receiving pharmacotherapy only (38.1 +/- 14.2 mg/day). Of the 230 children for whom titration identified an optimal treatment, 17% continued both the assigned medication and dosage throughout maintenance. The mean number of pharmacological changes per child was 2.8 +/- 1.8 (SD), and time to first change was 4.7 months +/- 0.3 (SE). CONCLUSIONS: For most children, initial titration found a dose of MPH in the general range of the effective maintenance dose, but did not prevent the need for subsequent maintenance adjustments. For optimal pharmacological treatment of ADHD, both careful initial titration and ongoing medication management are needed. PMID- 11211368 TI - School refusal in children and adolescents: a review of the past 10 years. AB - OBJECTIVE: To critically review the past 10 years of research on school refusal in children and adolescents. METHOD: Literature on school refusal published from 1990 onward was reviewed following a systematic search of PsycINFO. The review focuses on definitional issues, epidemiology and school refusal identification, diagnostic considerations, family functioning, assessment, treatment, and follow up studies. RESULTS: While definitional and conceptual issues are still evident, promising developments have occurred in relation to assessment and treatment practices and understanding of the family context of school refusal. CONCLUSIONS: From a clinical viewpoint, school refusal cases require comprehensive assessment and treatment. Advances have been made in the treatment of school refusal. However, additional controlled studies evaluating interventions for school refusal are needed. PMID- 11211369 TI - Treatment of school refusal: one-year follow-up. AB - OBJECTIVE: To conduct a 1-year follow-up of anxious-depressed school-refusing adolescents who participated in an 8-week study of imipramine versus placebo, each in combination with cognitive-behavioral therapy. METHOD: Sixty-five percent (41 of 63) of the randomly assigned subjects returned for follow-up evaluation, which consisted of diagnostic interviews, clinician rating scales for anxiety and depression, family functioning measure, and a questionnaire regarding interim treatments and school programs. RESULTS: From the adolescent and/or parent perspective, 64.1% met criteria for an anxiety disorder and 33.3% met criteria for a depressive disorder. Remission rates and acquisition rates for specific anxiety and depressive disorders were determined. In the follow-up period, 67.5% received at least one psychotropic medication trial and 77.5% had outpatient therapy. Higher level of somatic complaints on the Anxiety Rating for Children Revised Physiological subscale at baseline predicted more severe depression on the Children's Depression Rating Scale-Revised at follow-up (p = .029). CONCLUSIONS: In this naturalistic follow-up study, there was high utilization of mental health interventions. In addition, a substantial number of subjects met criteria for anxiety and/or depressive disorders 1 year after treatment. Investigation of duration of acute treatments and evaluation of maintenance treatments for school refusal is needed. PMID- 11211370 TI - Evaluation of a preventive intervention for maltreated infants and toddlers in foster care. AB - OBJECTIVE: To determine the effectiveness of an intervention designed to improve outcomes for infants and toddlers in foster care. METHOD: Records were reviewed for all children who were adjudicated as in need of care in a specific parish in Louisiana between 1991 and 1998. This period included 4 years before and 4 years after a comprehensive intervention was implemented. Children adjudicated between 1991 and 1994 were the comparison group, and those adjudicated between 1995 and 1998 were the intervention group. RESULTS: After the intervention, more children were freed for adoption and fewer children were returned to their birth families than before the intervention. There was no difference in length of time in care before and after the intervention. With regard to the same child returning in a subsequent incident of maltreatment, relative risk reduction for the intervention group ranged from 53% to 68%. With regard to the same mother maltreating another child subsequently, relative risk reduction for the intervention group ranged from 63% to 75%. CONCLUSIONS: A comprehensive preventive intervention for maltreated infants and toddlers in foster care substantially reduced rates of recidivism but had no effect on length of time in care. PMID- 11211371 TI - Fluvoxamine for children and adolescents with obsessive-compulsive disorder: a randomized, controlled, multicenter trial. AB - OBJECTIVE: To determine the safety and efficacy of fluvoxamine for the treatment of children and adolescents with obsessive-compulsive disorder (OCD) with a double-blind, placebo-controlled, multicenter study. METHOD: Subjects, aged 8 to 17 years, meeting DSM-III-R criteria for OCD were recruited from July 1991 to August 1994. After a 7- to 14-day single-blind, placebo washout/screening period, subjects were randomly assigned to fluvoxamine 50 to 200 mg/day or placebo for 10 weeks. Subjects who had not responded after 6 weeks could discontinue the double blind phase of the study and enter a long-term, open-label trial of fluvoxamine. Analyses used an intent-to-treat sample with a last-observation-carried-forward method. RESULTS: Mean Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) scores with fluvoxamine were significantly (p < .05) different from those with placebo at weeks 1, 2, 3, 4, 6, and 10. Significant (p < .05) differences between fluvoxamine and placebo were observed for all secondary outcome measures at all visits. Based on a 25% reduction of CY-BOCS scores, 42% of subjects taking fluvoxamine were responders compared with 26% taking placebo. Forty-six (19 fluvoxamine, 27 placebo) of 120 randomized subjects discontinued early. Adverse events with a placebo-adjusted rate greater than 10% were insomnia and asthenia. CONCLUSIONS: Fluvoxamine has a rapid onset of action and is well tolerated and efficacious for the short-term treatment of pediatric OCD. PMID- 11211372 TI - Effects of modafinil in children with attention-deficit/hyperactivity disorder: an open-label study. AB - OBJECTIVE: To examine the effect of once-daily dosing of modafinil, a stimulant that has a long duration of action, on clinical features of attention deficit/hyperactivity disorder (ADHD) in children. METHOD: An open-label design was used to compare the Conners Parent and Teacher Rating Scale-Revised (L) (CPRS, CTRS), the ADHD Rating Scale-IV, and the Test of Variables of Attention (TOVA), without and with medication, in children with ADHD. Eleven children with ADHD, ranging in age from 5 to 15 years, took modafinil for an average of 4.6 weeks. RESULTS: Average TOVA ADHD scores improved by 2.43 SD (p = .0009). CTRS and CPRS ADHD index T scores improved by an average of 14.1 (p = .0009) and 17.7 points (p = .001), respectively. The mean ADHD Rating Scale-IV scores improved from the 88th percentile to the 75th percentile (p = .047). One subject withdrew from the study because of an adverse event that was resolved completely with medication withdrawal. Other side effects were mild and responded to dose adjustment. No subjects required more than one dose per day. CONCLUSIONS: Modafinil may be a useful once-daily treatment for children with ADHD. Further study using a double-blind, placebo-controlled design is needed. PMID- 11211373 TI - Open trial of interpersonal therapy in adolescents with moderate to severe major depression: effectiveness of novice IPT therapists. AB - OBJECTIVE: To evaluate the effectiveness of interpersonal therapy (IPT) implemented by well-supervised, novice IPT therapists in treating adolescents with moderate to severe mood disorders of lengthy duration. METHOD: Twenty-five adolescents with moderate to severe major depression, lasting an average of 8 months, received 12 weeks of IPT. All participants were assessed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children Present and Lifetime Version, the Beck Depression Inventory (BDI), the Hamilton Rating Scale for Depression (HRSD), and the Children's Global Assessment Scale (C GAS) at baseline and follow-up. RESULTS: The majority of participants improved substantially on the BDI, the HRSD, and the C-GAS; 84% met remission criteria on the HRSD (score < 7); and 80% met remission criteria on the BDI (score < 10). CONCLUSIONS: Results demonstrate that IPT is effective in treating moderately to severely depressed adolescents, that IPT is effective with depression lasting several months, and that IPT can be effectively implemented by well-supervised clinicians with no prior training in IPT. PMID- 11211374 TI - Teacher reports of DSM-IV ADHD, ODD, and CD symptoms in schoolchildren. AB - OBJECTIVE: To examine the prevalence of DSM-IV symptoms of attention deficit/hyperactivity disorder (ADHD), oppositional defiant disorder, and conduct disorder and age, gender, and comorbidity differences between ADHD subtypes. METHOD: Teachers completed a DSM-IV-referenced symptom inventory for 3,006 schoolchildren aged between 3 and 18 years. RESULTS: The screening prevalence rate of ADHD behaviors was 15.8%; rates for individual subtypes were 9.9% for inattentive, 2.4% for hyperactive-impulsive, and 3.6% for combined. The inattentive type was relatively uncommon in preschool children (3.9%), whereas the hyperactive-impulsive type was least common in teenagers (0.8%). Screening prevalence rates were higher for African-American (39.5%) than white (14.2%) students, but did not vary significantly (p < .05) as a function of geographic region or socioeconomic status. ADHD subtypes were rated as more impaired than the non-ADHD group on most measures and were easily differentiated on the basis of comorbid symptoms, social skills impairment, and special education services. CONCLUSIONS: The findings of this and similar studies show relatively high convergence for the prevalence of ADHD behaviors and differences between ADHD subtypes. PMID- 11211375 TI - Problems with null hypothesis significance testing. PMID- 11211376 TI - Genetics of childhood disorders: XXIII. ADHD, Part 7: The serotonin system. PMID- 11211377 TI - Writing an op-ed commentary on nursing. PMID- 11211378 TI - Nurses' use of palliative care practices in the acute care setting. AB - This study examines the reported use of palliative care practices by nurses caring for terminally ill patients in the acute care setting. Randomly selected nurses (n = 180) from six randomly selected hospitals in Connecticut completed a self-administered questionnaire. Factors associated with use of palliative care practices were examined by using bivariate and multivariate analyses. Most nurses surveyed (88.5%) reported using palliative care practices when caring for their terminally ill patients. Factors associated with greater use included greater knowledge about hospice, having practiced nursing for less than 10 years, and having had hospice training in the past 5 years. A substantial proportion of nurses reported that they never discuss hospice (51.7 per cent of nurses) and prognosis (26.6 per cent of nurses) with their terminally ill patients. Educational preparation (bachelor's degree versus less education) was not associated with greater use of palliative care practices. Palliative care practices are commonly used by nurses in the acute care setting. However, many report having limited training and substantial gaps in knowledge about hospice among this group of nurses, suggesting greater attention to palliative care and hospice may be warranted in nursing educational programs. PMID- 11211379 TI - Developing BSN leaders for the future: the Fuld Leadership Initiative for Nursing Education (LINE). AB - The Helene Fuld Leadership Initiative in Nursing Education (LINE) program was designed to enhance beginning leadership competencies of baccalaureate nursing students. Given the increasing need for strong and effective leadership throughout the health care system, and the demands new graduates encounter as they move into practice, the LINE program is built on the premise that leadership skills must be instilled at the undergraduate level. The program achieves its goal through an intensive 5-day institute focused on assessing and developing the leadership competencies of nurse educators and their clinical partners to enable them to be effective agents of curriculum change in their home institutions. The institute also assists participants to redesign their baccalaureate nursing (BSN) curricula to ensure that students learn to: (1) work effectively within and across complex, integrated organizational and institutional boundaries; (2) think and act from the perspective of a system; and (3) communicate, negotiate, lead, and facilitate change within health care organizations. D. Goleman's (1998) framework of emotional intelligence, which addresses both personal competence (managing oneself) and social competence (handling one's relationships with others) provides the framework for operationalizing leadership in the BSN curriculum. To date, 26 BSN programs and their clinical partners have participated in the LINE program, which has the potential to influence the beginning leadership development of more than 2,400 BSN students. Program outcomes reveal that education-practice collaboration, professional networking, individual leadership development of nurse educators and their clinical partners as change agents, and the integration of leadership experiences at all levels of the BSN curriculum are important in developing beginning leadership competencies in BSN students. PMID- 11211380 TI - Insights and inquiry. PMID- 11211381 TI - An application of an effective interdisciplinary health-focused cross-cultural collaboration. AB - The phenomenon of cross-cultural collaboration is not new. What is lacking in the literature, however, is a discussion of how health professionals from various cultures, collaborating together, have addressed their patients' health care needs to improve their quality of life. Because of increased interest in global health issues, it seems logical that health professionals from various countries form collaborative partnerships to investigate and address these health issues. Although treatments to health problems are offered, it is not generally communicated in the literature how cross-cultural collaboration played a role in managing the process to solve the problem. By applying the concepts for global managers outlined by P. R. Harris and R. T. Moran (1996), this article describes how the investigators established a successful cross-cultural collaboration for conducting health research between teams in the United States and Russia. PMID- 11211382 TI - Cultural diversity: getting to a viewing point. PMID- 11211383 TI - An external mentor program: stimulus for faculty research development. AB - This article describes a faculty development model to stimulate rapid growth in research and scholarship in a school of nursing during an institution-wide initiative to strengthen the research stature of the university. The program was designed to establish targeted mentoring relationships with productive researchers from institutions outside the home institution to assist faculty with research program development. The external mentor program is described along with the methods of implementation and outcomes after 2.5 years. The success of this program has led to adoption of the model by other schools in the university. PMID- 11211384 TI - Scholarship of practice for a practice profession. AB - At a time of shrinking resources, rapidly changing health care environments, and increased demands for solutions to pressing health issues, concerns regarding the relevance of nursing research for practice are again being raised. After the national debate surrounding definitions of scholarship across disciplines and having established respectability for past and current contributions to knowledge development, nursing may now begin to reconceptualize what constitutes scholarship in a practice profession. This article addresses two central questions related to the scholarship of nursing practice: (1) How is scholarship of practice in a practice of profession defined? and (2) What characteristics differentiate the new conceptualizations of scholarship of practice from traditional research models? The results include a delineation of scholarship of practice and a differentiation of characteristics between scholarship of practice and traditional research approaches. Implications for nursing education are also addressed. PMID- 11211385 TI - Ethics instruction in nursing education. PMID- 11211386 TI - Describing the RN-BSN learner perspective: concerns, priorities, and practice influences. AB - This focus group study describes the concerns and priorities of women who are Registered Nurse Students (RNs) students (N = 35) enrolled in RN-Bachelor of Science in Nursing (BSN) programs located within a large metropolitan region. The study also explores the influences of BSN education on the nursing practice patterns of the RN students from the participants' viewpoints. Five focus groups were conducted. Findings revealed that accurate academic advisement, curriculum flexibility, and computer technology are important to RN-BSN students. RNs were concerned about the demands of the changing health care environment, meeting multiple and competing role demands, and meeting the financial demands of school. Although the participants did not believe that BSN education had affected their direct care of patients, they identified changes in indirect care practices. This study suggests that nursing school deans, administrators, and faculties should offer opportunities for RNs to develop skills in assertiveness, problem solving, and communication. Additionally, study findings suggest that RNs need the opportunity to reflect on various strategies for incorporating their new knowledge into their established practice. PMID- 11211387 TI - Education. Blueprints for the future. PMID- 11211389 TI - Self-insurance with assurance. PMID- 11211388 TI - Survey of distance technology use in AACN member schools. AB - The American Association of Colleges of Nursing surveyed its members by using a 104-item instrument to determine the state of the art in distance technology use. Survey results indicated a recent acceleration of course offerings through distance technology at all levels of nursing education. The most cited reason for this was to improve access to nursing education. Resources for distance technology tended to reside in public, rather than private, institutions. Trends were for greater use of video and computer-based technologies. Although technology use is increasing, computers and other technologies are not used in the didactic or clinical educational experience in many schools. Areas for further evaluation are identified. PMID- 11211390 TI - First annual hospital OPPS update published. PMID- 11211391 TI - The next challenge: employee training on privacy, security. American Health Information Management Association. PMID- 11211392 TI - Using OIG guidances for long-term success. PMID- 11211393 TI - Is wireless technology at hand for healthcare? PMID- 11211394 TI - Understanding HIPAA transactions and code sets. AB - The recently published final regulations for transactions and code sets under HIPAA are the light at the end of the tunnel in the quest for uniform healthcare standards--and the first step on a long road to HIPAA implementation. What are the standard transactions and code sets? This article takes an in-depth look. PMID- 11211395 TI - A quick take on clearinghouses. PMID- 11211396 TI - When health information and fiscal management meet. AB - HIM professionals have skills that can allow them to contribute to the bottom line in many ways. The author describes areas where HIM expertise can make a difference in evaluating an organization's fiscal performance through analysis of services driven by health information. PMID- 11211397 TI - Ten steps to successful chargemaster reviews. AB - Is your chargemaster current, compliant, and comprehensive? In the age of APCs, healthcare facilities would do well to answer these questions regularly. Here's how an HIM professional can help. PMID- 11211399 TI - Long-term care cost accounting: simple is often better. PMID- 11211398 TI - A new approach to chargemaster management. AB - After examining their charge description master management processes, HIM professionals, in conjunction with clinical and support departments, redesigned and automated several practice aspects. Turnaround times were reduced and end users are happier. Here's how they did it. PMID- 11211400 TI - Want to know more? Looking for more information about billing and reimbursement issues? Save this handy resource list. PMID- 11211401 TI - Creating a diverse HIM work force. PMID- 11211402 TI - Information security: it takes a community. PMID- 11211403 TI - Practice brief. Health informatics standards and information transfer: exploring the HIM role. American Health Information Management Association. PMID- 11211404 TI - Knowledge management: another avenue for HIM professionals. PMID- 11211405 TI - CPT changes for 2001. PMID- 11211406 TI - Lead your own image marketing campaign. PMID- 11211407 TI - Sorting out the inpatient rehabilitation PPS. PMID- 11211408 TI - Developing cost-effective, productive physician relations. PMID- 11211409 TI - AMCs need to develop capacity for innovation, Commonwealth Fund report says. PMID- 11211410 TI - Health care leaders no longer can afford to wing it when it comes to finance. PMID- 11211411 TI - After trend of IDS integration, some organizations have chosen to disintegrate. PMID- 11211412 TI - Marketing vs. the 800-pound gorilla. PMID- 11211413 TI - Hospitals can reduce costs, improve quality by adopting proven risk management guides. PMID- 11211414 TI - Bush, Congress offer opportunities, risks. PMID- 11211415 TI - Nematodes: worms of the world. AB - Intestinal nematodes remain a world health issue. Their ubiquitous nature makes them difficult to control, and treatment is ineffective when the source of the infection can not be eradicated. International travel and immigration from developing countries have effectively increased the numbers of people infected in the US, especially in the northeast and southern coastal areas. It is important to provide sensitive and accurate methods to diagnose these parasites. Additionally, the WHO and other agencies must remain vigilant and continue their efforts to improve the health of vulnerable populations throughout the world. PMID- 11211416 TI - Process redesign in the clinical laboratory: a success story. PMID- 11211417 TI - Sifting through the data to find the best LIS. PMID- 11211418 TI - Reviewing admission necessity. PMID- 11211419 TI - Weight gain and longterm complications with atypical antipsychotics. PMID- 11211420 TI - State of South Dakota's child: 2000. AB - For the second consecutive year, 1999 brought an increase in the total number of births in South Dakota. Low birth weight newborns also increased during this year to 5.9%, representing the highest rate observed since 1974. Although the total percent of low birth weight increased, the percent of very low birth weight slightly decreased. Also observed is an increase in the use of prenatal care in the first trimester of pregnancy. The infant mortality rate for the state decreased slightly but remains higher than what is noted nationally. The rate of neonatal mortality is also slightly higher than the national rate. South Dakota's rate of post neonatal mortality remains considerably higher than the national rate but did decrease in 1999. The special topic of this year's report is brain development and the role of early experience. The state's new Bright Start program for pregnant women and their infants is described. PMID- 11211421 TI - Peyote use during pregnancy. AB - Peyote is a substance with varied potential. Used properly it may be a spiritual aid but used in excess, it can be a hallucinogenic agent with teratogenic potential. There is a growing community of devout people who use it as part of their religious observance. The active ingredient, mescaline, has been linked to a specific group of fetal abnormalities when the substance is used inappropriately. PMID- 11211422 TI - Immunohistochemistry in surgical pathology is here to stay. PMID- 11211423 TI - Heads above the crowd. PMID- 11211424 TI - Hack attack. PMID- 11211425 TI - Expert for hire. PMID- 11211426 TI - End of the paper chase. PMID- 11211427 TI - It's all about people. For many healthcare CIOs, fulfillment requires more than money. PMID- 11211428 TI - Track training electronically. Using technology to avoid the bottlenecks that human foibles can create. PMID- 11211429 TI - Extensive monitoring during auditory brainstem implant surgery. AB - In patients with reduced auditory nerve function, for example due to tumour removal or an accident, hearing rehabilitation can be elicited by an auditory brainstem implant (ABI). The electrode array of the ABI manufactured by Cochlear Ltd., Sydney, consists of 21 circled contacts in a silicon carrier. This is inserted in the lateral recess of the fourth ventricle. Since 1996, in Hannover eight patients have been implanted with a cochlear ABI Nucleus 21 + 1. All of them were profoundly deaf on both sides due to neurofibromatosis type 2 (NF2). To find the optimal electrode position during surgery, a multimodal monitoring by auditory evoked potentials (AEP), electromyography (EMG) and somatosensory evoked potentials (SEP) was performed. When monitoring AEPs, the function of the implant can be checked first by the stimulus artefact. By analysing the AEPs in more detail, the optimal positioning of the electrode on the cochlear nucleus can be found. If systems other than the auditory system are stimulated this will be revealed in one or more of the AEP, EMG and SEP recordings. According to the literature, AEPs stimulated by an ABI consist of three vertex positive peaks with latencies shorter than 4 ms. Typical AEPs are correlated with good post-operative hearing sensation. Comparing these AEPs with AEPs stimulated acoustically or electrically at different sites of the auditory system, it can be assumed that the first peak corresponds to J3, the second to J4 and the last to J5. From this comparison it can also be concluded that no potentials should occur later than 5 ms. This corresponds to our findings. Post-operatively, side-effects occurred when areas of the electrode array were stimulated that showed potentials with latencies longer than 5 ms intra-operatively. Our results indicate that monitoring is an essential aid for the surgeon in finding the optimal electrode position. Positioning solely with reference to anatomical landmarks may not be enough to find the optimal functional position. PMID- 11211430 TI - Auditory brainstem implant in auditory rehabilitation of patients with neurofibromatosis type 2: Hannover programme. AB - An auditory brainstem implant (ABI) is indicated for patients suffering from bilateral neural deafness. The most affected patients are those with neurofibromatosis type 2 (NF2). An implantation is possible either at the same time as, or after, surgical removal of an acoustic neuroma. This paper demonstrates the results of eight out of 11 patients with NF2, seven of whom received an ABI after tumour removal. Pre-operatively, all of them were deaf. Post-operatively, the first fitting served to determine the individual stimulation parameters for each electrode. The stimulation-dependent side-effects were eliminated by reducing the stimulus intensity without causing negative effects on the hearing with the ABI. Only in one case was an open set understanding achieved within the first year. However, all patients had a better speech understanding when they combined their hearing with the ABI and their lip reading abilities. There is no correlation between the performance with ABI and the tumour size or the duration of deafness. PMID- 11211431 TI - Auditory brainstem implantation in primates: lessons for human surgery and application. AB - We report on the surgical technique for surface electro-auditory prosthesis (EAP) implantation, pathological changes occurring at the cochlear nucleus complex (CNC), and its relation with electrical stimulation. Fourteen Macaca fascicularis were operated upon for a translabyrinthine bilateral auditory neurectomy, and simultaneous unilateral EAP implantation. Six animals were not stimulated, and the remaining eight were connected to an external active device. Stimulation was planned for 1000 hours. Biotolerance to the materials was adequate without significant reactions in the CNC surface, but an ependymal reaction. Lesions attributed to surgical trauma were also found. Two animals being stimulated could not complete the planned course due to cable break or EAP extrusion. One stimulated animal developed an asymptomatic brainstem abscess. A good knowledge of CNC topography is required to avoid surgical trauma. Externally connected devices may facilitate extrusion of the EAP or ascending infections. PMID- 11211432 TI - Surgical experiences in 58 cases using the Nucleus 22 multichannel auditory brainstem implant. AB - Patients with bilateral total deafness due to lesions of the vestibulocochlear nerve can be treated by electrical stimulation of the second auditory neuron. A 22-channel multi-electrode implant with transcutaneous transmission was developed that allows the selection of the most useful electrodes. Acoustic neuromas were removed from 49 out of 58 patients by ENT surgeons and neurosurgeons working in collaboration and using either a translabyrinthine or suboccipital approach. The central electroauditory prosthesis was implanted in the same procedure. Six patients were deaf after previous acoustic neuroma surgery without recurrence, three had diagnoses other than neurofibromatosis type 2 (NF2). There were no complications due to the implantation procedure. Side effects could be excluded by stimulation of the auditory electrodes alone. Most of the patients used their ABI daily. They reported perception of different sounds and frequencies, enhancement of lip-reading ability, and three of the patients were able to use the telephone. PMID- 11211433 TI - Stimulation of the cochlear nucleus with multichannel auditory brainstem implants and long-term results: Freiburg patients. AB - Since 1992 18 patients with bilateral retrocochlear deafness have been provided with a multichannel auditory brainstem implant (ABI). The surgical procedure implies tumour removal and ABI implantation in one stage. Most implantations were via the translabyrinthine approach. The long-term follow-up varied between nine and 80 months. In one case auditory perception could not be achieved and in a second case post-operative stimulation was not possible as the subject died due to lung emboli. In all the other cases auditory perception was achieved and only two subjects became non-users during the follow-up period. The presented long term results suggest that deaf neurofibromatosis type 2 patients regain acoustic contact with the environment, enlarge their communication skills and improve their quality of life by using a multichannel auditory brainstem prosthesis. PMID- 11211434 TI - Topodiagnosis of deafness: strategy for treatment of neurofibromatosis type 2. AB - Neurofibromatosis type 2 (NF2) causes bilateral hearing loss due to tumour growth in the cerebellopontine angle. We report the results of promontory testing and transtympanic electrocochleography on subjects with deafness due to NF2 referred for an auditory brainstem implant. All 19 ears tested revealed loss of cochlear microphonics. Nine ears (mainly without previous treatment) revealed auditory perception during promontory stimulation, indicating cochlear deafness. One of these subjects has been successfully provided with a cochlear implant. The other 10 ears (mainly after previous surgery) revealed negative promontory stimulation, indicating additional retrocochlear deafness. These findings indicate that neurofibromas initially cause a cochlear deafness, so that a cochlear implant can be used if the auditory nerve can be preserved. This option has to be considered in rehabilitating patients with bilateral tumours due to NF2. PMID- 11211435 TI - Auditory brainstem implants: current neurosurgical experiences and perspective. AB - The objective of this study was to present aspects of the current treatment protocol, such as patient evaluation and selection for therapy, multimodality monitoring for optimal auditory brainstem implant (ABI) positioning and radiological evaluation, that might have an impact on the functional results of ABI. Out of a series of 145 patients with bilateral vestibular schwannomas 10 patients received an ABI, eight of which are reported here. Patient selection was based on disease course, clinical and radiological criteria (according to the Hannover evaluation and prognosis scaling of neurofibromatosis type 2 (NF2)), extensive otological test battery and psycho-social factors. ABI placement was controlled by multimodality electrophysiological monitoring in order to activate the auditory pathway and to prevent false stimulation of the cranial nerve nuclei or long sensory or motor tracts. Results of hearing function were correlated with patients' ages, duration of deafness, tumour extension, tumour-induced compression or deformation of the brainstem, and numbers of activated electrodes without any side-effects. Out of 59 patients with pre-operative deafness eight patients received an ABI of the Nucleus 22 type. All these patients became continuous users without any side effects and experienced improved quality of life. Speech reception in combination with lip-reading was markedly improved, with further improvement over a long period. A short duration of deafness may be favourable for achieving good results, while age was not a relevant factor. Lateral recess obstruction may necessitate a more meticulous dissection, but did not prevent good placement of the ABI in the lateral recess. Pre-existing brainstem compression did not prevent good results, but brainstem deformation and ipsi- and contralateral distortion were followed by a less favourable outcome. Among the factors that can be influenced by the therapy management are the selection of patients with a slow progressing NF2 disease, a short duration of deafness, a careful analysis of brainstem deformation and consideration of either side for implantation. Long-standing brainstem deformation might not lead to recovery, but instead lead to a low number of active electrodes and possibly only moderate results. ABI treatment is a safe procedure that can increase a patient's quality of life considerably. ABI placement along with neurophysiological control helps to prevent side effects and to improve acoustic activation. Further studies on structural and functional changes of the brainstem after previous tumour compression and distortion should increase our understanding and facilitate a decision on the best side for ABI implantation. PMID- 11211436 TI - Retrosigmoid approach for auditory brainstem implant. AB - The present paper reports our experience with the surgical retrosigmoid transmastoid (RS-TM) technique for implanting auditory brainstem implants (ABIs). From April 1997 to August 1998, four patients with neurofibromatosis type 2 (NF2) were operated on for vestibular schwannoma removal with ABI implantation. The subjects (three men and one women) ranged in age from 22 to 31 years. Tumour size ranged from 12 to 30 mm. A classical RS-TM approach was performed. After tumour excision, identification of landmarks (VIIth, VIIIth and IXth cranial nerves, choroid plexus) to the foramen of Luschka was carefully carried out. The choroid plexus was partially removed and the tela choroidea divided and deflected. The floor of the lateral recess of the fourth ventricle and the convolution of the dorsal cochlear nucleus became visible. The electrode array was then inserted into the lateral recess and placed in the correct position with the help of electrically-evoked auditory brain stem responses. Auditory sensations were induced in all patients with various numbers of electrodes. Different pitch sensations could be identified with different electrode stimulation. Details of the results are presented. In our series, the RS-TM approach represents the elective route for ABI insertion. PMID- 11211437 TI - First Croatian auditory brainstem implantation. AB - A deaf female patient was diagnosed with bilateral acoustic neurinomas. Diagnosis incorporated the standard audiological battery for sensorineural hearing loss, computed tomography and magnetic resonance imaging. The left side had been operated on four years previously in another clinic using the suboccipital approach. The auditory brainstem implant surgery was performed on the 'second side' using the same approach. It was an uneventful operation with good anatomy and no serious post-operative complications. Post-operatively, the patient performed exceptionally well, with up to 50 per cent of words recognized in the opened set and 85 per cent in the closed set, both without lip-reading. PMID- 11211438 TI - First auditory brainstem implantation in Poland: auditory perception results over 12 months. AB - Auditory brainstem implants (ABIs) are a modern method of treatment of total bilateral deafness in cases of extracochlear origin. In most cases therapy is applied in patients with neurofibromatosis type 2 (NF2). This paper presents the results of surgical treatment and rehabilitation in a 28-year-old woman with bilateral, multiple tumours of the central nervous system causing total deafness. Simultaneous removal of the tumours and implantation of ABI allowed treatment of the potentially lethal pathology and hearing restoration. Improving auditory skills and excellent tests results were noted in the year following implantation. PMID- 11211439 TI - Multichannel auditory brainstem implantation: the Australian experience. AB - The multichannel auditory brainstem implant (ABI) provides the potential for hearing restoration in patients with neurofibromatosis type 2 (NF2). Programmes for auditory brainstem implantation have been established in two Australian centres. Eight patients have been implanted under the protocol of an international multi-centre clinical trial. Three patients had ABI insertion at the time of first side tumour removal, four at second side tumour removal and one after previous bilateral surgery where there was some residual tumour. The translabyrinthine approach was used in all cases. Successful positioning of the electrode array was achieved in seven of eight patients, all of whom achieved auditory perception with electrical stimulation. Intra-operative electrically evoked auditory brainstem response testing was successful in four patients and was useful in confirming correct electrode position. In six cases post-operative psychophysical and auditory perception testing demonstrated that useful auditory sensations were achieved. Five of these patients regularly used the implant. In one patient electrode placement was unsuccessful and only non-auditory sensations occurred on stimulation. In the remaining patients non-auditory sensations were minimal and avoidable by selective electrode programming. Auditory brainstem implantation should be considered in patients with NF2. The greatest benefit is seen in patients without debilitating disease who have non-aidable hearing in the contralateral ear. PMID- 11211440 TI - Multichannel auditory brainstem implant: US clinical trial results. AB - Since 1994, a US Food and Drug Administration clinical trial evaluated the multichannel auditory brainstem implant (ABI) on 92 subjects with neurofibromatosis type 2 (NF2). The trial has shown that 85 per cent of patients receive auditory sensations. A small number of patients demonstrate a clinically significant degree of open-set sentence recognition in the sound-alone condition; however, when the ABI is combined with lip-reading cues, 93 per cent of patients demonstrate improved sentence understanding at three to six months. In addition, the majority of recipients report daily use of their devices, and satisfaction with the decision to receive the ABI. PMID- 11211441 TI - First auditory brainstem implant in the Czech Republic. AB - In the Czech Republic, the first implantation of a stimulation electrode into the brainstem was performed on 11 January 1999 in the Department of ORL, Head and Neck Surgery, The First Medical Faculty, Charles University in Prague, University Hospital Motol. The selected patient was a 40-year-old woman with neurofibromatosis type 2 (NF2) who had previously undergone bilateral vestibular schwannoma surgery. Both tumours had been radically removed, the left-sided tumour in 1987, the right-sided one in 1988. She had been completely deaf since the last operation, i.e., for 11 years. The surgery was realized by the international cooperation of three teams. Placement of the electrode pad of the Nucleus CI21 + 1M system on the ventral and dorsal cochlear nuclei was performed. Electrically evoked auditory brainstem responses (EABRs) proved the correct position of the electrode array. The post-operative course was uneventful. Six weeks after the surgery the patient received her speech processor. Since that time, the patient already absolved several sessions of a speech processor tune up. She uses the device as an aid in lip-reading. No adverse or pathological side effects have been observed. The patient was the 45th person in Europe to receive an ABI and the first in the Czech Republic. PMID- 11211442 TI - Anatomical variations of landmarks for implantation at the cochlear nucleus. AB - A knowledge of the microanatomy of the cochlear nucleus complex and its variations is essential for successful implantation and for the design of stimulation devices. One hundred cerebellopontine angle specimens were dissected under surgical conditions using the Zeiss NC31 surgical microscope. The topographical anatomy of the exit of the vestibulocochlear nerve, the cochlear nucleus and the surface of the medulla and their relation to the surrounding structures was recorded and measured. The mean distances between the exits of the VIIth and VIIIth cranial nerves were 4.7 +/- 0.9 mm, between the VIIth and IXth 6.3 +/- 1.2 mm and between the VIIIth and IXth 5.5 +/- 1.0 mm. The visible area of the cochlear nucleus covered a square of 10.0 +/- 2.9 by 3.3 +/- 1.0 mm. A major AICA-loop had to be re-routed in 17 per cent of specimens. The taenia of the choroid plexus was present in 92 per cent and had to be cut in 51 per cent in order to enter the foramen of Luschka, that had a mean size of 3.5 by 2.0 mm. It was wide open in 24 per cent, open only after incision of the arachnoid in 53 per cent, functionally closed but opened by extensive dissection in 18 per cent and anatomically occluded in five per cent of the specimens. The typical straight vein at the cochlear nucleus leading to the entrance of the foramen of Luschka was found in 76 per cent of specimens. Constant anatomical landmarks are very helpful for finding the cochlear nucleus, but variations may endanger dissection and implantation in a remarkable number of cases. PMID- 11211443 TI - [Anomalties of the interatrial septum and latent atrial vulnerability in unexplained ischemic stroke in young adults]. AB - Seventy-four consecutive patients (18 to 55 years) underwent programmed atrial stimulation in the investigation of unexplained ischaemic stroke after a full work-up including transoesophageal echocardiography to exclude abnormalities of the interatrial septum (patent foramen ovale and/or atrial septal aneurysm). The parameters recorded during atrial electrophysiological investigation were: the effective atrial refractory period, loco-regional intra-atrial conduction, the index of latent atrial vulnerability and the inducibility by the extrastimulus technique. Seventy five per cent of patients with a patent foramen ovale and/or an atrial septal aneurysm were inducible compared with only 38% of patients with normal interatrial septa on transoesophageal echocardiography (p = 0.001). Fifty two per cent of patients with an anomaly of the atrial septum had latent atrial vulnerability compared with 26% of those with normal transoesophageal echocardiography (p = 0.02). These results confirm the relationship between atrial septal anomalies and latent atrial vulnerability in unexplained ischaemic stroke of young adults. PMID- 11211444 TI - [Heart surgery under cardiopulmonary bypass during the neonatal period remains a high-risk procedure]. AB - Congenital Heart disease with a poor prognosis has to be operated early but with an acceptable surgical risk and a good chance of survival. The aim of this study was to analyse the indications, the operative mortality and medium-term survival of neonates undergoing cardiac surgery under cardiopulmonary bypass from 1991 to 1998. Three hundred and twenty nine operations were programmed in 326 neonates, 18% (329/1805) of all open heart surgical procedures. Anatomical detransposition of the great arteries was the commonest operation (N = 226). Correction was complete (biventricular) in 97% of cases (317/326). Twenty-eight neonates died. The operative mortality was 8.5%, much higher than that of children of 3 months or over (1.5%; p < 0.0001). There were 8 late deaths, all in the first postoperative year. The overall medium-term survival rate was 88.9 +/- 1.7%. It was 100% after correction of truncus arteriosus without interruption of the aortic arch; 94.2 +/- 1.5% after anatomical detransposition; 85.7 +/- 9.4% after commissurotomy of aortic stenosis; 79.2 +/- 8.3% for all the complex forms of interruption of the aortic arch; 75 +/- 9.7% for total anomalous pulmonary venous drainage and 42.9 +/- 18.7% after the Norwood palliative procedure of hypoplastic left heart syndrome. The authors conclude that early cardiac surgery saves the large majority of neonates suffering from complex congenital cardiac disease with poor prognosis. Survival stabilises one year after the operation. Other techniques or treatments are necessary to lower present surgical risk (8.5%) to that of surgery under cardiopulmonary bypass of children over 3 months of age (1.5%). PMID- 11211445 TI - [Efficacy of colchicine in recurrent acute idiopathic pericarditis]. AB - Acute idiopathic pericarditis is complicated by recurrence in 15 to 30% of cases. The preventive treatment of recurrences is not well codified. Aspirin, non steroidal anti-inflammatory drugs and corticoids are the commonest prescribed treatments. The objective of this study was to assess the value of colchicine in the prevention of recurrences of acute idiopathic pericarditis. Twenty-eight cases of recurrent acute pericarditis (2 episodes, 1 month between each episode) admitted to a department of internal medicine between 1989 and 1999 were reviewed. Analysis was concentrated on the 13 idiopathic forms. The subjects were 7 women and 6 men with an average age of 41 years (10-62) at the time of the first episode of acute pericarditis. These 13 patients were treated with colchicine (1 to 2 mg/day) after failure of conventional treatment (aspirin 13/13, NSAID 13/13, steroids 9/13 and pericardiocentesis 3/13). Ten patients were followed up regularly (6 months after starting colchicine) and were improved with respect to number, duration and intensity of their recurrences. The average duration of colchicine therapy was 17 +/- 14 months (6-48). Progressive withdrawal of NSAID and steroids was obtained in 8/10 cases. The authors conclude that colchicine is useful in the prevention of recurrence of acute pericarditis. It may be proposed as treatment of choice, especially in the idiopathic forms. PMID- 11211446 TI - [Normal coronary angiography. Survival and functional status at 6 years]. AB - Despite the development of non-invasive diagnostic techniques, the absence of significant coronary stenosis is observed in 10 to 30% of coronary angiographic studies. The authors report the survival and functional status at 6 years of 172 consecutive patients with symptoms of angina without significant angiographic coronary stenosis. The average age was 60.8 years with a sex ratio of 1.1 and chest pain as the indication for coronary angiography in over 90% of cases. The global mortality after an average of 75.6 months follow-up was 11%, lower in women (8.5%) than in men (13.3%) with an annual mortality of 16.3 per thousand. Sudden death was observed in 4 patients and a third of deaths was of cardiac origin. The persistence of symptoms was reported by 58% of patients, mainly atypical chest pain. Despite the result of coronary angiography, nearly half of the patients were followed up annually by a cardiologist, two thirds remained on anti-anginal therapy, 20% were treated by psychotropic agents and hospital admission to the cardiology department was required in 22% of cases during follow up. None of the patients had myocardial infarction. Survival and myocardial function after normal coronary angiography therefore appear to be good in contrast with the functional status of these patients. PMID- 11211447 TI - [Does patient age influence the indications for investigating asympatomatic Wolff Parkinson-White syndrome?]. AB - Sudden death may be the presenting symptom of a Wolff-Parkinson-White syndrome. Electrophysiological investigation is the best method of identifying high risk cases. The aim of this study was to determine whether this investigation should be proposed to all patients, irrespective of age. Transoesophageal stimulation was performed in 85 asymptomatic patients with the Wolff-Parkinson-White syndrome. Of the 85 subjects, 13 were under 20 years of age, 30 under 30 years, 15 under 40 years, 16 under 50 years and 11 between 50 and 69 years of age. A protocol of incremental stimulation until 2nd degree AVB was attained and programmed atrial stimulation with one or two extrastimuli delivered on 2 paced cycles (600 and 400 ms) was used under basal conditions and with Isoprenaline. A malignant form of the condition was defined as the demonstration of two abnormalities: rapid conduction in the bundle of Kent (over 240/min) under basal conditions or over 300/min after Isoprenaline, and if it induced sustained atrial fibrillation (> 1 min). The results were: [table: see text] In conclusion, the number of malignant forms of the Wolff-Parkinson-White syndrome is exactly the same, irrespective of age. Elderly patients remain at risk of malignant WPW syndrome because of the increased incidence of atrial fibrillation. Therefore, the authors recommend systematic evaluation of this syndrome if the patient has an active life-style especially with regard to sporting activities. PMID- 11211448 TI - [Treatment of left atrial thrombosis by low-molecular-weight heparin. A preliminary study of 6 cases]. AB - Left atrial thrombosis is a serious complication of atrial fibrillation because of its embolic potential, especially for the cerebral circulation. These thrombi are usually treated by oral anticoagulation. The authors studied the efficacy and tolerance of a low molecular weight heparin. Enoxaparin, in the treatment of this condition. This was a prospective study carried out over a 1 year period. Patient recruitment came from the transoesophageal echocardiography laboratory: of 15 thrombi detected, 6 were treated by ambulatory Enoxaparin therapy. Five of the 6 patients had no signs of left atrial thrombosis after 3 weeks of Enoxaparin therapy. The left atrial thrombus of the 6th patient remained hyperechogenic and had decreased in length from 27 to 24 mm. No cases of bleeding, haematoma, embolism or thrombopenia were observed with this treatment. This preliminary study shows that low molecular weight heparin may be used as an alternative to classical oral anticoagulation for the treatment of left atrial thrombosis. PMID- 11211449 TI - [White coat hypertension]. AB - White coat hypertension and the white coat effect are common clinical problems. Although they have similar names, they do not correspond to strictly identical entities. The white coat effect is an increase in blood pressure induced by the physician. It may be observed for all degrees of mean blood pressure and it is usually assessed by the difference between conventional and ambulatory blood pressure values. White coat hypertension is a qualitative status associating clinical hypertension and "normotension" outside the physician's office. In practice, the application of these definitions presents many difficulties. The usual methods of evaluating the white coat effect are a poor marker of the true effect as measured by continuous blood pressure monitoring. White coat hypertension has many definitions, both with respect to the threshold of clinical hypertension and to that of ambulatory normotension. Any attempt at evaluating the prognosis of these two conditions are faced with these considerations. However, the cardiovascular consequences which result appear to be mild and, usually, do not justify drug therapy. Their principal implications are above all diagnostic as they may lead to the erroneous assumption of severe or drug resistant hypertension. PMID- 11211450 TI - [Mitral valve prolapse, arrhythmias and sudden death]. AB - Some of the classical concepts of mitral valve prolapse (MVP) should be reviewed in the light of recent publications. It is a condition, according to strict echocardiographic criteria excluding near physiological abnormalities, which affects 2 to 3% of the adult population in the industrialised world. Only repetitive atrial arrhythmias and complex ventricular arrhythmias are more common in this condition than in control groups, the differences being more pronounced in cases of mitral regurgitation. The risk of syncope or sudden death is 0.1% per year, hardly any different to that of the rest of the general adult population (0.2%). However, this risk may attain 0.9 to 2% in cases with mitral regurgitation. The causes of sudden death are unclear (haemodynamic, neurohumoral, arrhythmic, etc...), although there is evidence in favour of malignant ventricular arrhythmias. Detailed clinical, electrophysiological, isotopic and anatomopathological studies have raised doubts as to the direct responsibility of the vascular malformation (or its eventual consequences on the atrial and ventricular chambers) in this mode of fatal outcome. On the other hand, localised or diffuse myocardial disease is often observed, usually a- or pauci-symptomatic, associated with MVP, the responsibility of which is more plausible. Therefore, the physician should adopt a flexible attitude towards these patients, reassuring those with benign symptoms at low risk and following up or actively treating the rarer malignant forms (especially familial, syncopal with mitral regurgitation and/or severe arrhythmias). PMID- 11211451 TI - [Ambulatory management of chronic cardiac failure. Possible value of health networking]. AB - Cardiac failure is one of the commonest medical conditions. It usually affects the elderly and is responsible for repeated hospital admission with its high cost for the social security. Several attempts at ambulatory management in certain countries have been successful. Their application may be possible in France. The setting up of health systems like the ones which exist for diabetes, could be a solution to the problem. PMID- 11211452 TI - [Coronary subclavian steal syndrome after internal mammary artery bypass grafting. A cause of severe postoperative recurrent myocardial ischemia]. AB - A 65-year-old underwent a triple bypass: internal artery mammary-descending coronary artery, aorta diagonal-lateral coronary (sequential). Three weeks later he started to have severe angina pectoris with ST depression in anterior EKG leads. A left transradial coronary angiography was performed. The examination showed a total occlusion of the left subclavian artery 2 cm after the aortic arch and a retrograde flow in the internal mammary artery (IMA). Via transfemoral approach, angiography showed the patency of the aorto-veinous sequential graft and a retrograde flow through anastomosis in the left mammary artery. The patient underwent a reimplantation of the IMA on the brachiocephalic artery. One month later the patient is doing well without chest pain. A coronary subclavian steal syndrome should be suspected in case of recurrent ischaemia after IMA bypass, particularly if there is more than 20 mmHg systolic pressure differential between the arms. Left transradial approach achieved diagnostic in case of total left subclavian artery occlusion. PMID- 11211453 TI - [Idiopathic left ventricular aneurysm presenting with ventricular tachycardia. A case report]. AB - Left ventricular aneurysm presenting with ventricular tachycardia was observed in a 48 year old man. Aetiological investigation was negative. The differences between aneurysm and diverticulum and the aetiologies of aneurysms are discussed. The treatment of the arrhythmias caused by this condition is discussed with the help of a review of the literature. PMID- 11211454 TI - [Anomalous origin of coronary arteries from three separate ostia in the right sinus of valsalva. A case port and review of the literature]. AB - The authors report the case of a patient undergoing coronary angiography for a lateral myocardial infarction related with atherosclerosic lesions but associated with a rare anomalous origin of all three coronary arteries from separate ostia in the right sinus of Valsalva. Anomalous origin of coronary arteries from the opposite sinus are potentially serious especially among young subjects and when a vessel runs between the aorta and pulmonary artery. Clinical presentation, angiographic diagnostic and treatment strategies are discussed. PMID- 11211455 TI - The use of lasers in dermatology. AB - There are now a range of lasers capable of effective treatment of vascular, pigmented and other skin lesions with a high degree of selectivity. Understanding the complex interactions between laser irradiation and often diverse lesion morphology is the key to determining the appropriateness of treatment. PMID- 11211456 TI - Human oocyte cryopreservation. AB - Despite early success with sperm and embryo cryopreservation, human oocyte cryopreservation has met with limited success both in terms of survival and subsequent fertilization. However, compared with embryo cryopreservation, oocyte freezing has great potential for eliminating the ethical and legal problems of embryo storage. PMID- 11211457 TI - Investigating eosinophilia in patients returned from the tropics. AB - In patients who have returned from the tropics, eosinophilia usually signifies infection with worms. This paper gives an approach to investigating these patients systematically. The key element is a good travel history leading to targeted investigations. PMID- 11211458 TI - Simvastatin: building on success. AB - Over a decade after launch, simvastatin remains the most widely-prescribed statin in the UK. This has resulted from a growing body of long-term outcome data, a steadily expanded range of indications, an extended dose range and proven cost efficacy. PMID- 11211459 TI - Vaginal hysterectomy. AB - Vaginal hysterectomy represents the ultimate minimal access hysterectomy. The indications for the procedure extend well beyond those of prolapse. Good training and advances in surgical technique allow the removal of enlarged fibroid uteri as well as vaginal oophorectomy. This article also considers the complications which may follow. PMID- 11211460 TI - Pharmacological treatment of depression: the role of paroxetine. AB - Depression is reaching epidemic proportions in the western world. With each successive generation more people are becoming more severely depressed at a younger age. PMID- 11211461 TI - Acute medical emergencies: the physician's role. PMID- 11211462 TI - Provision of an electronic library at the clinical frontline: evaluation of impact on hospital medical staff. AB - Doctors need convenient access to the latest information if they are to meet the demands of clinical governance and evidence-based medicine. Forest Healthcare NHS Trust used its intranet to provide clinical areas with direct 24-hour access to library materials. PMID- 11211464 TI - Beware of groin pain in the elderly athlete. PMID- 11211463 TI - Revision total hip arthroplasty without blood transfusion. PMID- 11211465 TI - Vault haematoma after vaginal hysterectomy. PMID- 11211468 TI - Laser revascularization in the management of coronary artery disease. AB - In recent years, laser therapy has been evaluated for the treatment of patients with angina who have coronary artery disease which is not amenable to conventional revascularization techniques. The results of transmyocardial revascularization and percutaneous myocardial revascularization are reviewed. PMID- 11211466 TI - Post-intubation tracheal stenosis. PMID- 11211467 TI - The future of pathology in the UK: modernization or rationalization? PMID- 11211469 TI - [Treatment of hypertension in the prevention of cardiovascular damage]. PMID- 11211470 TI - [Difficulties regarding the development of palliative treatment]. AB - Palliative care is the branch of medicine which studies and applies the best way to cure when the traditional method is no longer able to interrupt the course of the disease until death. Two of the main characteristics of this kind of cure is to offer a support system to help the patient's family during the illness and to involve psychological care of the patient. The different approach with the patient and the new role of the doctor are just two obstacles of the spread of the palliative cure. PMID- 11211471 TI - [Pasteurella pestis: pardon for infamy]. PMID- 11211472 TI - [Etiology and epidemiology of extrauterine pregnancy]. AB - In the last years, ectopic pregnancy has become a frequent problem, especially in the industrialized countries. Women aged 30-40 years are mostly affected. Infact, in this ten-years period, more and more women feel the desire of pregnancy at ripe age, first of all because of their job. This study shows 136 cases of extrauterine pregnancy, observed at our hospital, I and II Institute of Obstetric and Gynecological Clinic of "Policlinico Umberto I" in Rome from January 1997 to December 1999. The object of this analysis is to determine the characteristics and ethiologic factors of this pathology. PMID- 11211473 TI - Age-related trend for blood pressure circadian rhythm in normotensive healthy subjects: estimates provided by the clinospectror method. AB - The present study investigates how blood pressure (BP) circadian rhythm (CR) changes in its rhythmic properties as a function of chronological age in normotensive healthy subjects (NHS). The age-related trend for BP CR was investigated via the Clinospectror method, a periodic-linear analysis of regression for rhythmic parameters. The study was performed on 437 NHS (219 males and 218 females, ranging in age from 1 year to 102 years), who were monitored in their 24-h BP via a noninvasive automated recorder. An age-related trend was detected for the three properties of BP CR, i.e., mesor (M), amplitude (A) and acrophase (cent). Such a trend was positive for M and A, and negative for cent. According to the clinospectrometric formula, the BP CR can be classified as a "dianaclinous rhythm", i.e., a rhythm which increases in its oscillatory level and extent with advancing years. The documented age-related trend for the rhythmic properties suggests that the biological clock which regulates the BP CR in human beings undergoes a resetting of its mechanisms of tonic, amplitude and phasic modulation as a function of chronological age. The readjustment of the pressure clock may be regarded as one of the physiological features which characterize the aging process in human beings. PMID- 11211475 TI - [Assessment of hepatocyte AgNORs expression in chronic hepatopathy]. AB - The high incidence of liver chronic diseases has aroused strong interest in researching and trying to discover the biomolecular basis. In this context the study of nucleolar organizing regions could be interesting as a prognostic factor for chronic hepatitis and for liver neoplastic disease. The Authors report on the results of their study performed on 39 selected samples from 4 different inflammatory hepatic disorders. PMID- 11211474 TI - [Causality relationship of drug adverse reactions: experience in the use of HIV protease inhibitors]. AB - PURPOSE: To establish the exact cause and effect relationship between protease inhibitors (PIs) and adverse events. MATERIALS AND METHOD: Prospective, cohort, multicenter study on HIV-positive patients who are beginning treatment with a PI. Causal relationships are evaluated using the RUCAM algorithm. RESULTS: Since the beginning of the study 1207 patients have been enrolled. Average time of observation is 10.7 months. To date, 784 adverse events have been observed, distributed as follows: excluded 3.8%, improbable 18.5%, possible 41.3%, probable 30.1%, and highly probable 6.3%. Saquinavir shows a statistically significant difference in the rate of non-correlated events with respect to other groups. CONCLUSIONS: Over 20% of adverse events during PI treatment are shown to be non correlated to these drugs. Saquinavir shows the highest rate of non-correlated events. PMID- 11211476 TI - [Hospices from the DPCM 20/1/2000 perspective: requirements to ensure a better quality of "residual life"]. AB - INTRODUCTION: In this paper, the authors analyse the increasing number of oncological patients, above all the terminal ones. The aim of hospice is to guarantee a high quality residual life. Hospice must not be regarded as a place of sweet death; on the contrary it's a hospital where palliative cares take place. It is, then, an alternative to home in the most critical phases of illness. CONSIDERATIONS: Despite a lasting interest in the matter, a law setting up a standard has been lacked until DPCM of 20/1/2000 that established structural, technological and managerial requirements for the centres of palliative cares. New hospices must be built in sunny places, in close contact with nature and easily reachable both by private and public means of transport. The law provides for three areas: a residential area, an evaluation and therapy area and a general area of support. PMID- 11211477 TI - [Anaplastic, insular, and medullary carcinoma of the thyroid]. AB - Anaplastic carcinoma, insular carcinoma and medullary carcinoma (both familiar and sporadic forms) represent the 7-25% of all thyroid tumors. Anaplastic carcinoma is one of most aggressive human tumors and the therapeutic options proposed have failed to improve the prognosis of these patients. Insular carcinoma is a not well known thyroid neoplasia described for the first time in 1984 and showing intermediate biological behaviour between differentiated and anaplastic forms. Medullary carcinoma arises from parafollicular"C" cells of the gland and then may be considered a neuroendocrine tumor. Choice therapy is surgery, tiroxine is only substitutive, familiar screening is mandatory. Chemotherapy (dacarbazine or cisplatin and doxorubicine), radiotherapy and recently octreotide anologues, may be useful for relapsing not operable forms. PMID- 11211478 TI - Recent advances in the molecular analysis of human malignant mesothelioma. AB - PURPOSE: To evaluate the role of asbestos, somatic genetic alterations, and simian virus 40 (SV40) in the formation of malignant mesothelioma (MM). DESIGN: To review recent cytogenetic and molecular genetic advances in MM. RESULTS: Exposure to asbestos is a major factor contributing to the development of most MMs. The accumulation of recurrent cytogenetic deletions in most MMs suggests a multistep process in this malignancy characterized by the loss and/or inactivation of multiple tumor suppressor genes (TSGs). Karyotypic, comparative genomic hybridization (CGH), and loss of heterozygosity (LOH) analyses of MMs have demonstrated frequent deletions of specific chromosomal regions within 1p, 3p, 6q, 9p, 13q, 15q, and 22q. Positional candidate gene approaches have identified TSGs within two of these regions, i.e., CDKN2A at 9p21 and NF2 at 22q12, which are frequently altered in MMs. In addition, recent studies have demonstrated the presence and expression of SV40 in many MMs. Proposed mechanisms by which asbestos and SV40 contribute to the development of MM are reviewed. CONCLUSIONS: The identification of new TSGs involved in MM and understanding the role of these genes and of SV40 in the pathogenesis of this malignancy may lead to design of more effective therapeutic strategies. PMID- 11211480 TI - [Diabetes mellitus and pancreas. The brilliant intuition of a great Italian clinician of the 19th century]. PMID- 11211479 TI - [Familial Mediterranean fever: report of a case]. AB - Familial Mediterranean fever is an autosomal recessive hereditary disease characterised by recurrent fever, poliserositis, chest and/or abdominal pain. Up to date diagnosis is based on clinical symptoms, familial anamnesis and response to colchicine. It is an inflammatory reaction affecting serosal tissues but until recently different hypotheses have been suggested to explain the greatly increased chemotactic activity of the polymorfonuclear leucocytes. Identification of the function of the MEFV gene on chromosome 16 and its protein allows us to understand the pathogenesis of familial Mediterranean fever as well as provides a new diagnostic test and therapeutic measures. We describe a case of an young patient and review the literature. PMID- 11211481 TI - [Diagnosis of Helicobacter pylori infection: a new test]. PMID- 11211482 TI - It's Bush. Now What? PMID- 11211483 TI - Partisan politics spells trouble for health care. PMID- 11211484 TI - Healthcare finance: the opportunities are wide open. PMID- 11211485 TI - The defined-contribution plan: the next generation of healthcare financing. AB - In response to rising health insurance premiums, many purchasers of coverage are evaluating the possibility of implementing defined-contribution health insurance plans. Under a defined-contribution plan, employers or the government pay a specified portion of the premium, and the consumer chooses a plan from a menu of options, paying the balance of the premium based on their plan selection. A shift to a defined-contribution model will have far-reaching implications for consumers, employer and government purchasers, payers, and providers. Providers will face changes in consumption patterns and the need to develop a brand image, market their strengths directly to consumers, educate consumers about their services and pricing, and reconfigure infrastructures to be able to respond efficiently to consumer demands. PMID- 11211486 TI - HIPAA privacy standards raise complex implementation issues. AB - In November 1999, under the mandate of the Health Insurance Portability and Accountability Act (HIPAA) of 1996, HHS issued proposed standards to protect the privacy of electronically transmitted personal health information. With publication of the final standards due soon, healthcare organizations must prepare to implement new processes and information systems to comply with the HIPAA requirements. The privacy standards are intended to accomplish three broad objectives: define the circumstances in which protected health information may be used and disclosed, establish certain individual rights regarding protected health information, and require that administrative safeguards be adopted to ensure the privacy of protected health information. Among the required administrative safeguards are designation of a privacy officer, implementation of compliance training programs for all applicable staff, establishment of a complaint system, and implementation of appropriate sanctions for violations of privacy requirements. PMID- 11211487 TI - Percentage compensation arrangements: suspect, but not illegal. AB - Percentage compensation arrangements, in which a service is outsourced to a contractor that is paid in accordance with the level of its performance, are widely used in many business sectors. The HHS Office of Inspector General (OIG) has shown concern that these arrangements in the healthcare industry may offer incentives for the performance of unnecessary services or cause false claims to be made to Federal healthcare programs in violation of the antikickback statute and the False Claims Act. Percentage compensation arrangements can work and need not run afoul of the law as long as the healthcare organization carefully oversees the arrangement and sets specific safeguards in place. These safeguards include screening contractors, carefully evaluating their compliance programs, and obligating them contractually to perform within the limits of the law. PMID- 11211488 TI - Nursing homes face quality-of-care scrutiny under the False Claims Act. AB - The Federal government has brought a series of civil actions against nursing home operators for alleged violations of the Federal False Claims Act. According to government prosecutors, if a nursing home submits Medicare or Medicaid claims for care the government considers substandard, the claims are false for that reason alone. However, the government's theory ignores the fact that the detailed Federal statutes and regulations that govern nursing homes, as well as the agencies that enforce them (the "regulatory enforcement scheme"), allow homes that have been found to provide substandard care to continue receiving Medicare and Medicaid payment while they correct their deficiencies. Until recently, most of the cases had settled, and the government's theory had not been addressed in a published court decision. In a recent case, however, a Federal judge refused to grant the defendant facility's motion to dismiss and permitted the government's case to proceed. PMID- 11211489 TI - Process-centered revenue-cycle management optimizes payment process. AB - By implementing a process-centered revenue cycle, healthcare organizations and group practices can achieve a seamless payment process with clear lines of accountability to achieve target outcomes. The integrated, end-to-end, revenue cycle process involves four key components: jobs, skills, staffing, and structure; information and information systems; organizational alignment and accountability; and performance measures and evaluation measures. The Henry Ford Health System (HFHS), based in Detroit, Michigan, exemplifies the type of results that are achievable with this model. HFHS includes a group practice with more than 1,000 physicians in 40 specialties. After implementing a process-centered revenue cycle, HFHS dramatically improved registration and verification transactions and optimized revenues. PMID- 11211490 TI - Differing definitions of "provider" can affect Medicare payment. PMID- 11211491 TI - Setting priorities for implementation of electronic transaction standards. PMID- 11211492 TI - Setting the highest ethical leadership standards ensures a higher standard of results. PMID- 11211493 TI - Data trends. Miscoding leads to lost revenue. PMID- 11211494 TI - Heterogeneity and differential expression of MUP proteins as a genetic basis of the physiological activity of androgen-dependent pheromones. PMID- 11211495 TI - Increased corticofugal plasticity after pyramidotomy in adult rats. PMID- 11211496 TI - Modulation of pain of different genesis by microelectrostimulation. PMID- 11211497 TI - Prolonged regulatory effect of thyroliberin on conditioned vegetative responses in hedgehogs. PMID- 11211499 TI - The role of the smooth endoplasmic reticulum in neuronal adaptation to fatiguing stimulation. PMID- 11211498 TI - The mechanism of the synchronization of pulse flows in neural networks of the visual system. PMID- 11211501 TI - Changes in the functional asymmetry of the brain in wrestlers. PMID- 11211500 TI - Correlation of the EL-4 lymphoma cell apoptosis with the expression of heat shock proteins. PMID- 11211502 TI - Characteristics of the EEG interhemispheric asymmetry in right- and left-handed subjects as a reflection of the interaction between the cerebral cortex and cerebral regulatory systems. PMID- 11211503 TI - Metabolic/food programming of enzyme systems in digestive and nondigestive organs of rats. PMID- 11211504 TI - Opioid modulation of pain threshold in fish. PMID- 11211506 TI - Formation of the centers of early spring phytoplankton bloom in Kola Bay. PMID- 11211505 TI - The defensin receptor: a possible mechanism responsible for reduced excitability of the neuronal sensory membrane. PMID- 11211507 TI - The relationship of the number of hydrobiont species with morphometric characteristics and the productivity of lakes. PMID- 11211508 TI - Contribution of soil to atmospheric CO2 balance in Russia. PMID- 11211509 TI - Energetics of green cell stress resistance: a concept. PMID- 11211510 TI - The role of specific cell surface in phytoplankton productivity. PMID- 11211511 TI - Spring production cycle of phytoplankton in the Kara Sea. PMID- 11211512 TI - Ciliary locomotion of the mollusk is different from that of the planaria. PMID- 11211513 TI - Specific structural features of the pectoral arch and phylogenetic relations in some mammalian taxa. PMID- 11211514 TI - A new subspecies of the European bison, Bison bonasus montanus ssp. nov. (Bovidae, Artiodactyla). PMID- 11211515 TI - Effect of red wood ants on carabid behavior: experimental studies at the individual level. PMID- 11211516 TI - Effect of zooplankton pressure on the dependence of the chlorophyll a concentration on the total phosphorus content in water. PMID- 11211517 TI - Multiple effects of B chromosomes in maize populations. PMID- 11211518 TI - The circulatory system of phoronid larvae. PMID- 11211519 TI - Probable mechanisms of the gravitational sensitivity of cells. PMID- 11211520 TI - In vitro and in vivo effects of a perfluorocarbon emulsion on cells of the rat central nervous system. PMID- 11211522 TI - Disorders of intraorganismal systemic communications during carcinogenesis. PMID- 11211523 TI - Overlapping genes and variability of the genetic code. PMID- 11211524 TI - Cracking down on ecstasy. Law enforcement is treating the 'hug drug' as if it were the next cocaine. Is it? PMID- 11211521 TI - The influence of sea squirt lectin on growth and adhesion of HeLa tumor cells. PMID- 11211525 TI - China's bitter harvest. The theft and sale of human body parts. PMID- 11211526 TI - New-style mammograms detect cancer. So do the old. Either way you wait. PMID- 11211527 TI - A thyroid problem can mimic almost anything. PMID- 11211528 TI - MMR vaccination and autism: the tip of the iceberg. PMID- 11211529 TI - Successful immunization of children: barriers and strategies. PMID- 11211530 TI - Diabetes and hypertension in the Americas. PMID- 11211531 TI - Causal link between MMR vaccination and autism: fact or fiction? PMID- 11211532 TI - The legal and ethical issues raised by the practice of alternative and homeopathic medicine in the Caribbean. PMID- 11211533 TI - The feasibility of a porcine model of acute coronary occlusion and reperfusion using off-pump coronary artery bypass grafting. AB - We developed an open-chest porcine model of acute coronary occlusion and surgical reperfusion, and attempted to prevent intra-operative ischaemic ventricular fibrillation (VF) by a Retrograde Intracoronary Glyceryl trinitrate (RIG) infusion into the occluded vessel. Five Yorkshire pigs (weight 50 +/- 1.1 kg), randomized into 3 groups, underwent median sternotomy under general anaesthesia. One pig (Group 1, control) underwent sternotomy and pericardiotomy only. Four pigs underwent acute left anterior descending (LAD) coronary occlusion. Two pigs were not reperfused (Group 2). Two pigs underwent surgical reperfusion (Group 3) via left internal mammary artery (LIMA) grafting to the LAD using the Off-Pump Coronary Artery Bypass (OPCAB) technique. Ischaemic injury was assessed using 7 lead electrocardiography (ECG) and transthoracic/epimyocardial echocardiography (ECHO). Group 1: transient intraoperative hypotension and VF occurred. Successful resuscitation and 10-week survival (until sacrifice) with normal left ventricular (LV) function was achieved. Group 2: there were ECG and ECHO evidence of acute LV ischaemic dysfunction in both pigs. The surviving pig had persistent anterior hypokinesis at 8 1/2 months. The other died intra-operatively following progressive ischaemic LV dysfunction despite resuscitative attempts. Group 3: the surviving pig had normal LV function at 8 months. Initial anterior LV akinesis normalized within 7 days. The other developed post-occlusion haemodynamic instability and died intra-operatively despite reperfusion. In this porcine model, acute LAD artery occlusion modified by the novel RIG infusion technique, followed by surgical reperfusion (OPCAB) is feasible. This model would facilitate further development of OPCAB surgical expertise and understanding of the pathophysiology of ischaemia-reperfusion injury. PMID- 11211534 TI - Early metabolic defects for developing diabetes mellitus among offspring of patients with type 2 diabetes are independent of gender. AB - The aim of the study was to investigate if the female offspring of patients with Type 2 diabetes have more metabolic defects for developing diabetes mellitus than their male counterparts. Thirty-four offspring (10 males, 24 females) of patients with Type 2 diabetes mellitus aged 28.9 +/- 1.5 years (mean +/- SEM) underwent a standard oral glucose tolerance tests (OGTT; 75 g glucose in 300 ml water). Anthropometric indices, plasma lipids and blood pressure were measured while insulin resistance (IR) and sensitivity (%S) were assessed using the Homeostasis Model Assessment (HOMA) method. All the offspring had normal glucose tolerance but high HOMA-derived IR values (27.2 +/- 4.2 vs. 22.5 +/- 2.7 pmol/mmol/l, p > 0.05) and low %S (48.1 +/- 5.1 vs. 50.6 +/- 3.9%, p > 0.05), all of which did not differ on gender comparisons. Multiple linear regression analyses suggest that gender had no influence on the outcome of the result (p = 0.37). Again, body mass index (BMI), fasting serum insulin, plasma glucose, triglyceride, total cholesterol, HDL-cholesterol and LDL-cholesterol were all similar in both genders (p > 0.05). The results suggest that though the offspring manifested metabolic defects for developing diabetes in later life, this susceptibility is independent of gender in the population studied. Further studies with a larger sample size are warranted to confirm these findings in this population. PMID- 11211535 TI - The influence of persistent hyperglycaemia on hyperfibrinogenaemia and hyperviscosity in diabetes mellitus. AB - The effect of hyperglycaemia on hyperfibrinogenaemia and its consequence on plasma viscosity was investigated in 69 diabetic patients during the course of hypoglycaemic treatment. Glycaemic control was assessed by measurement of glycosylated haemoglobin (HbA1). Plasma fibrinogen concentration (PFC) was determined by a clot-weight method. The relative plasma viscosity (RPV) was measured by capillary viscometry. The mean PFC and RPV were significantly (p < 0.001) elevated in the diabetic patients as compared with a non-diabetic control group. Both PFC and RPV showed a distinct, step-wise increase with progressively poorer glycaemic control. The data strongly indicate that persistent hyperglycaemia is associated with a frank hyperfibrinogenaemia and hyperviscous plasma in most of the diabetic patients studied. These abnormal haemorrheological changes could impact adversely on both the haemostatic process and circulation in diabetic patients. PMID- 11211536 TI - The efficacy of acarbose in type 2 diabetes mellitus in Jamaica. AB - The efficacy and tolerability of acarbose was studied in type 2 diabetic patients eating a typical Jamaican diet. The study was an open label parallel group study without placebo control. Of the 51 subjects recruited, five (9.8%) did not complete the study and were excluded from further analysis. Six (13%) of the remaining 46 had adverse side effects and did not complete the protocol. Of the remaining 40 (Gp A), acarbose was added to their previous regime of diet alone (n = 15), [Gp B], oral hypoglycaemic agents, OHAs (n = 17), [Gp C], or insulin (n = 8), Gp D]. In addition, during the run-in period all subjects had one session each with a dietitian and a diabetes educator. Over a 3-month period, significant reductions in average glucose (mmol) were observed in Gp B 10.5 +/- 1.1 to 8.4 +/ 0.9 (p < 0.027) and, from 11.0 +/- 1.0 to 8.7 +/- 0.7 (p < 0.01) in Gp C. Similarly, total glycosylated haemoglobin fell from 14.8 +/- 1.1% to 12.2 +/- 1.0% (p < 0.016) in Gp B, from 14.9 +/- 1.1 to 11.9 +/- 1.1% (p < 0.002) in Gp C, and from 14.1 +/- 1.4 to 11.8 +/- 1.4 (p < 0.02) in Gp D. Twenty-three per cent (23%) of the patients experienced flatulence; 7.5%, changes in bowel habits and 5%, abdominal cramps and discomfort. Acarbose is effective as monotherapy and as combination therapy with oral hypoglycaemic agents or insulin. Side effects were common, but tolerable. PMID- 11211537 TI - Coronary artery bypass graft outcome: the Trinidad and Tobago experience. AB - The study is retrospective review of the demographic, clinical, angiographic, and operative data of the first 205 consecutive CABG operations performed by Caribbean Heart Care at the Eric Williams Medical Sciences Complex (EWMSC), Trinidad and Tobago, between November 1993 and December 1997. The aim of the study was to determine the in-hospital and intermediate-term follow-up results. The mean age of patients was 59 +/- 10 years and 78% were male. Sixty-four per cent were of East Indian descent, whereas 16% were of African descent. Forty eight per cent of the patients were hypertensive, 46% were diabetic, 33% had hyperlipidaemia, 20% had a recent history of cigarette smoking and 16% were obese. Sixty-five per cent had a positive family history of ischaemic heart disease. The average time interval between angiography and surgery was 2.3 months. At the time of angiography, 63.5% of patients had Canadian Cardiac Society (CCS) class 3 or 4 angina. The mean ejection fraction was 61 +/- 15%. Wall motion abnormalities were seen in 67% of patients. Significant stenoses of the left anterior descending artery, right circumflex artery, circumflex and ramus coronary arteries were present in 91%, 78%, 54% and 5%, respectively. Many patients (67%) had severe diffuse disease on angiography. The mean intensive care stay was 2.2 +/- 0.8 days. In-hospital mortality was 3.9% (8/205). The most frequent post-operative complication was haemorrhage (2.6%). Acute renal failure occurred in 2.1%; pulmonary collapse, 1.6%; stroke, 1% and cardiac arrest, 1%. Both sternal wound infections and systemic sepsis occurred in 0.5%. Intermediate term follow-up data were obtained for 92% (189/205). The duration of follow-up ranged from 1 to 5 years (mean 3.7 years). During the follow-up period, 7 patients (3.4%) died. Angina severity was reduced from a mean CCS score of 2.61 +/- 0.95 before CABG to 1.22 +/- 0.55 at the time of follow-up (p < 0.0001). Overall 4-year mortality compared favourably with data from international studies. Among survivors, quality of life improved as evidenced by the reduction in the mean angina score. PMID- 11211538 TI - Surgery for patent ductus arteriosus. Still the gold standard. AB - The surgical treatment of Patent Ductus Arteriosus (PDA) at the University Hospital of the West Indies, Kingston, Jamaica, was examined over an eight-year period. The results of standard surgical modalities were comparable to large published series. A review of the literature regarding the treatment options for PDA does not support a change in management strategy in favour of non-surgical methods. The treatment of PDA at this centre has shown excellent long-term results, with minimal mortality and morbidity. PMID- 11211540 TI - Risk factors associated with ischaemic stroke in Guadeloupe. AB - We carried out a case control study at the University Hospital of Pointe-a-Pitre, Guadeloupe, during eight months. Seventy patients with ischaemic stroke and seventy age- and sex-matched controls were involved. A standard questionnaire reported clinical characteristics and medical history. Seventy-six per cent of patients suffered from hypertension. Obesity and diabetes were more frequent in the case group than in the control group. Serum creatinine concentration (86 vs 74 mumol/l; p < 0.001), total cholesterol (5.9 vs. 5.2 mmol/l; p < 0.001), apolipoprotein B (1.2 vs 1.0 g/l; p < 0.001) and lipoprotein (a) (82 vs 48 mg/dl; p < 0.001) were significantly higher in patients than controls. Multiple logistic regression analysis revealed that in addition to serum creatinine, serum apolipoprotein B, hypertension, obesity, serum lipoprotein (a) and diabetes mellitus were associated independently and significantly with ischaemic stroke. These findings have implications for clinical practice and further research particularly with respect to serum creatinine concentration as a marker of renal damage from hypertension and as a risk factor itself for cerebrovascular disease. PMID- 11211539 TI - The role of labelled red blood cell scintigraphy in the detection of acute gastrointestinal bleeding. AB - This paper describes the experience with 99m Technetium labelled red blood cell (99mTc RBC) scintigraphy in twenty-two patients presenting with acute gastrointestinal (GI) tract bleeding. Studies were positive in thirteen cases- eight from the lower GI tract and five from the upper. The data from surgical intervention were available in ten cases. Scintigraphy cannot diagnose the cause of GI bleeding, as it is a nonspecific study. Its usefulness lies in its ability to accurately diagnose the bleeding site, as was shown in this study where there was good surgical correlation. The simplicity, reproducibility and reliability of the technique, particularly when bleeding rates are low and intermittent, make it, in our view, the first line of investigation in any patient with suspected bleeding from the colon or upper GI tract if endoscopic evaluation is not possible in the latter. Its current under-utilisation in the Caribbean may be a reflection of the lack of nuclear imaging facilities. PMID- 11211541 TI - Impact on blood pressure control of a six-month intervention project. AB - The aim of this study is to evaluate the impact of a six-month structured education programme on blood pressure (BP) control in patients with uncontrolled hypertension. All patients attending the Specialist Hypertension Clinic, University Hospital of the West Indies (UHWI), between January 4 and March 29, 1999, with blood pressure > 140/90 mmHg (n = 80), were randomly divided into Group 1, cases (n = 42) and Group 2, controls (n = 38). A 40-item pretested questionnaire, administered at the baseline and final visits of both groups, elicited demographic, lifestyle and knowledge data. Group 1 attended monthly structured interventions for six months. Except for diastolic blood pressure among male controls, diastolic blood pressure and systolic blood pressure were significantly reduced at the end of the intervention period (p < 0.01). Knowledge improved among the male patients (p < 0.01). Among the female patients, activity scores were significantly increased (p < 0.01), weight (p < 0.05) and BMI (p < 0.05) were significantly reduced. There were no differences in these variables among the controls. This intervention had a benefit in blood pressure control. PMID- 11211542 TI - Evaluation of neonatal sepsis screening in a tropical area. Part I: Major risk factors for bacterial carriage at birth in Guadeloupe. AB - This prospective study reports on screening for neonatal sepsis among 3,372 live births out of 6,060 consecutive deliveries at the University Hospital of Pointe-a Pitre, Guadeloupe, during a 30-month period. Group B Streptococcus (GBS) was the most common pathogen, representing 46% (89/194) of positive blood cultures and 52% (335/637) of positive gastric aspirates. Although only 3,372 (55%) of all live births were screened, 637 (10%) had gastric bacterial carriage at birth; of those, 335 (5.5%) involved GBS. Similarly, there were 194 (3.2%) positive blood cultures, of which 89 (1.5%) involved GBS. In this report, all newborns who presented with a positive GBS blood culture had at least one of the external tests positive for GBS (gastric, ear canal, rectum and placenta). Thirty-seven per cent (14/38) of positive neonatal blood cultures occurred in newborns with foetid liquor while in deliveries with intrapartum fever 16.5% (32/195) of blood cultures were positive. In our clinical practice, characteristics that were evident in the delivery room (without knowledge of prenatal follow-up) such as foetid liquor, intrapartum fever, prolonged rupture of membranes, foetal tachycardia and meconium staining were associated with the great majority of neonatal sepsis. PMID- 11211543 TI - The impact of the Women's Centre of Jamaica Foundation programme for adolescent mothers on repeat pregnancies. AB - A random sample (n = 260) of primiparous Jamaican adolescent mothers (12-16 years old) who gave birth in 1994 in the parishes of Kingston and St Andrew, St Catherine and Manchester was selected from vital records and interviewed in 1998 for this historical cohort study. Among programme participants, the incidence of repeat pregnancy was 37 per cent compared with 60 percent among non-participants. Programme participation reduced the risk of one or more repeat pregnancies by 45 per cent with 95% confidence interval (0.22, 0.91). Programme participants were also 1.5 times (1.005, 2.347) more likely to complete high school than non participants; however, this effect did not achieve statistical significance. The results confirmed that the WCJF Programme exerts a considerable effect on the incidence of repeat pregnancy among participants. The benefits of programme participation were greatest among residents of the Kingston Metropolitan Area from single-parent, female-headed households with average monthly incomes below J$10,000, who wanted to continue their education after the first live birth. PMID- 11211544 TI - Risky behaviour in Jamaican adolescent patients attending a sexually transmitted disease clinic. AB - The prevalence of sexually transmitted diseases (STD) and risky behaviour patterns were studied in 165 adolescents attending a STD clinic in Jamaica. A standardised structured questionnaire, clinical algorithms for STD and serological tests for HIV and syphilitic infection were applied. High prevalences of risky behaviour including young age at onset of sexual activity, especially in boys, (mean age 12.5 +/- 2.5 years); unprotected sexual intercourse (only 4% used condoms consistently); multiple sexual partners (mean 3.8 +/- 2.4 and 1.8 +/- 1.2 for boys and girls, respectively) were found. Marijuana, used by 60% of the boys, was an independent risk factor for dysuria (adjusted Odds Ratio (OR), 2.0; 95% CI, 1.6-3.4). Repeated episodes of STD (33%), coinfection with HIV (1.2%), syphilis (1.2%) and teenage pregnancy (13%) were prominent findings. Educational strategies which promote behaviour intervention at an early age, frequent and consistent use of condoms, abstinence or delayed onset of sexual activity are essential to reducing the HIV/AIDS and STD risk in adolescents in Jamaica. PMID- 11211545 TI - The use of herbal teas and remedies in Jamaica. AB - We investigated the prevalence of the use of herbs among adults and children in Jamaica in 1996. Two concurrent surveys were conducted in randomly selected urban and rural areas: among adults and among caretakers of young children. From over 90% of the selected households, all caretakers of children under 6 years and one randomly selected adult (18 years or older) were interviewed using structured questionnaires. The 457 adults reportedly used 156 types of herbs: a mean of 6 +/ 3 (mean +/- standard deviation) by the urban adults, and 10 +/- 6 by the rural adults (t-test, p < 0.001). Almost 100% of respondents had at some time used herbs for teas or for treating illnesses. The most common method of preparation was by infusion or boiling in water, then adding sugar. Urban respondents, women and those who were employed were more likely to buy medicines than to use herbal remedies. One hundred and sixty-seven caretakers of 203 children under 6 years were interviewed. The mean number of herbs given to each child was between 2 and 3. The most common herbs were introduced within the first 6 months of life. Many caretaker factors were associated with herbal use. Public health implications include the potential toxicity of some herbs, the possibility that herbal teas given to young children may displace more nutritious foods and delay presentation to health care facilities. The findings will allow policy makers to target those most likely to use herbal preparations or to give them to young children, and target herbs to be analyzed for toxic or beneficial properties. PMID- 11211546 TI - Images and diagnoses. Synovial sarcoma. PMID- 11211547 TI - Images and diagnoses. Neurofibromatosis 1 (NF1)(Von Recklinghausen's disease). PMID- 11211548 TI - Rapid weight gain and benign intracranial hypertension in an AIDS patient on treatment with highly active anti-retroviral therapy (HAART). AB - We present the case of a 30-year-old woman with HIV/AIDS who experienced a 47% weight gain over a period of a year after commencing treatment with highly active anti-retroviral therapy (HAART) and went on to develop benign intracranial hypertension (BIH). She was not on any other medication associated with BIH. Although weight gain has been reported in patients on treatment with protease inhibitors, such gains have been minimal to moderate. We are unaware of any previous report of this degree of weight gain or BIH in a patient on protease inhibitors. PMID- 11211549 TI - Leptospirosis occurring in two children after fresh water immersion. AB - Leptospirosis is relatively uncommon in children. Two cases of severe leptospirosis occurred in teenaged boys who shared a common exposure via immersion in fresh water. While both patients had laboratory-confirmed leptospirosis, their symptoms differed in many respects. PMID- 11211550 TI - Severe pulmonary barotrauma. AB - Pulmonary barotrauma is a well-known but rarely seen complication of mechanical intermittent positive pressure ventilation. It is thought to be related to raised pressures within alveoli which lead to their eventual rupture and the subsequent development of respiratory embarrassment. Mishaps related to faulty one-way valves in the self-inflating, bag-ventilation devices commonly used in cardiopulmonary resuscitation (CPR) can, although rarely, lead to severe barotrauma. In this report, we describe a case of pulmonary barotrauma that appeared to be related to the "locking" of the "Ambu" bag's one-way valve in the inspiratory position during routine CPR. PMID- 11211551 TI - Pseudodementia in a twenty-one-year-old with bipolar disorder and vitamin B12 and folate deficiency. AB - A twenty-one-year-old female known to suffer from bipolar type I disorder developed features of a pseudodementia. Following prompt initial response to treatment with antidepressants, there was an early recurrence of cognitive impairment. Blood investigations confirmed a macrocytic anaemia and vitamin B12 and folate deficiencies. There was dramatic resolution of cognitive impairment after vitamin replacement. This suggested the occurrence of a reversible nutritional dementia and reinforced the need to rule out secondary organic causes of psychiatric symptoms even in patients previously diagnosed with a primary psychiatric disorder. PMID- 11211552 TI - Immunization of health care workers in the CARICOM countries. PMID- 11211553 TI - The politics and policies of caring for the elderly in an age of retrenchment: a symposium. PMID- 11211554 TI - The middle-class elderly and Medicaid financial eligibility policies for nursing home coverage. AB - Benefits for the middle-class elderly are generally distributed through such social insurance programs as Social Security Old Age Insurance and Medicare. The inclusion of long-term nursing home services for the elderly in Medicaid provides an opportunity to gauge the relationship of the "middle class" to a means-tested public assistance program. This article develops the analysis by focusing on the nature of the recent changes in financial eligibility, the use of so-called Medicaid planning strategies by the elderly to gain eligibility, and a discussion of competing scenarios for the evolution of these policies in the near future. The analysis finds that the middle-class elderly are both an elusive socioeconomic group and a powerful cultural symbol which simultaneously constrains and supports their inclusion as recipients of Medicaid nursing home coverage. PMID- 11211555 TI - Hospice: an organizational systems model for the integration of acute and long term care. AB - In recent years, the realization of a need for increased integration of acute care and long-term care (LTC) systems has grown. For the most part, however, a person requiring both types of care is treated as though he or she is two discrete individuals with separate needs. Organizations that have the integration of acute and LTC as a goal serve relatively small numbers of people. Integration efforts could be facilitated through the identification and application of an organizational systems model. Hospice can provide such a model. The hospice interdisciplinary team integrates not only multiple disciplines but also acute care and LTC. The hospice model is also appropriate from a financial standpoint in that Medicare hospice funding has employed a prospective payment system (PPS) since the inception of the Medicare Hospice Benefit. In this article, the application of the hospice model to the integration of the acute care and LTC systems in the U.S. is demonstrated, using a subsystem approach. PMID- 11211556 TI - Community and long-term facility care in Canada. AB - By 1969, federal/provincial agreements had resulted in universally-insured access to hospital and medical services for all Canadians. In the absence of similar agreements for community and long-term care, each province has designed, implemented, and modified its own policies and programs during the last three decades. However, the communal values and the universal access to hospital and medical services which underpinned the national health plan influenced these policies and programs. Over time, the provincial programs have become more similar to each other but significant differences remain. However, all the provincial programs combine the assessment and delivery of short- and long-term community care and almost all combine the assessment of need for community care with that for long-term facility care placement. This article examines the development and changes in the community care and long-term facility care sectors in Canada over the recent past. Despite financial constraints which have resulted in the downsizing of hospitals and reductions in the ratio of long-term beds to the population aged 75 and over, community care budgets have increased substantially during this time. The article also discusses the major issues now confronting Canadian policy-makers and planning in regards to these programs and explores the potential impact of factors such as changes in funding and the organization and delivery of other health care services on long-term care. PMID- 11211557 TI - Long-term care: a woman's world. AB - Long-term care is a world disproportionately comprised of women as consumers and as providers. Women comprise 75 percent of nursing home residents, 97 percent of professional caregivers, and the vast majority of family caregivers for elderly relatives at home. This article explores how and why long-term care, both in an institutional setting and home-based, is primarily utilized by women. The gender differences in the provision of care are also examined. The three key approaches to payment for long-term care (private payer, insurance, and Medicaid) are a focus with an emphasis on the role of Medicaid. Long-term care looms as an explosive issue and an accessible target for future program cutbacks. Since women are the predominant customers and providers of long-term care, this should be a priority issue for the feminist agenda. PMID- 11211558 TI - Long-term care financing: are current methods enough? AB - Financing long-term care services can be extremely cost prohibitive to the average United States citizen. Given the complex patchwork of multidisciplinary services that may be required, operational issues and system efficiencies often draw considerable attention. Notwithstanding these challenges, this article reviews the major sources of long-term care financing, including some lesser known options. Potential advantages and disadvantages are presented. A descriptive analysis of existing policies and consumer practices raises the question of whether recent incremental reforms will lead to future solutions for the major constituents most affected by their implementation. PMID- 11211560 TI - Neuroscience in the past--likely trends in future. PMID- 11211559 TI - U.S. medical students choice of careers and its future impact on health care manpower. AB - During the last 10-15 years, the health care system of this country has faced major challenges, among them, spiraling increases of health care costs, physician manpower maldistribution, excessive production of subspecialists, shortages of primary care physicians (family practice, general internal medicine, and general pediatrics), and lack of access to health care, predominantly among the poor and disadvantaged populations. As a way of shedding light on some of these challenges, the authors conducted a study among junior medical students from the University of Texas Medical School at Houston which focused on some of the factors that might influence medical students' choice of careers. In this article, the authors review the most salient findings for some of the problems that currently plague the health care system of this nation. Certainly, the outcome of this study has important educational and health service delivery implications not only in the United States but abroad as well, particularly among developing nations. PMID- 11211561 TI - Superior cervical ganglionectomy leads to dampening of amplitude of temperature rhythm in rats. AB - The circadian rhythm of body temperature (CRT) is a robust marker of the endogenous pacemaker function and is one of the most frequently studied rhythms. Melatonin, the main secretion of the pineal gland seems to have more of a thermomodulatory role in controlling the body temperature than having a direct role in thermoregulation. The sympathetic innervation to the pineal via the superior cervical ganglion determines the melatonin secretion, and superior cervical ganglionectomy (SCGx) decreases the secretion of melatonin. The present study was conducted on the Wistar rats (n = 12) to determine the role of melatonin in modulation of CRT. Adult male rats were either ganglionectomised (n = 6) or sham ganglionectomised (n = 6). Rectal temperature was recorded for CRT analysis. Cosinar analysis of the temperature record was done to get the acrophase, amplitude and mesor. Our results show that SCGx decreases the amplitude to the rhythm but has no effect on the mesor of the rhythm. Our study confirms that melatonin has little role to play in the thermoregulation and its role is mainly in thermomodulation. PMID- 11211562 TI - Serotonergic mechanism in imipramine induced antinociception in rat tail flick test. AB - Substantial evidence has accumulated that spinally projecting serotonergic neurons modulate nociception. However, the exact receptor subtypes that mediate the antinociceptive response of serotonin within the spinal cord continue to be a subject of debate. Therefore, we explored the effect of serotonergic system on imipramine induced antinociception by using 5-Hydroxytryptamine-3 (5HT3) receptor antagonist ondansetron and 5-Hydroxytryptamine-2 (5HT2) receptor antagonist mianserine, and depletion of brain 5-Hydroxytryptamine (5HT) with p-chlorophenyl alanine (PCPA). Male wistar strain rats were pretreated with either ondansetron (0.5 mg/kg, i.p.) or mianserine (1 mg/kg, i.p.). After 15 minutes, rats received injection of imipramine (10 mg/kg). Nociception was assessed by tail-flick method. Imipramine (2 mg, 5 mg, 10 mg, and 20 mg/kg) produce antinociceptive response in the dose dependent manner. Prior treatment with 5HT3 antagonist, Ondansetron and 5HT2 antagonist, mianserine reduce the antinociceptive response of imipramine. In PCPA treated rats imipramine (10 mg/kg) failed to produce antinociception. These results indicate that the 5HT plays an important role in imipramine induced antinociception. PMID- 11211564 TI - Body weight regulatory mechanisms evidenced on meal-time restrictions. PMID- 11211563 TI - Development of differential tolerance to the sedative and anti-stress effects of benzodiazepines. AB - Differential degree of tolerance has been reported to develop for anticonvulsant, sedative and skeletal muscle relaxant effects of benzodiazepines (BZDs). Acute treatment with BZDs reportedly reduces the formation of gastric stress ulcers and attenuates stress-induced immunosuppression. The present study investigates whether tolerance develops to these antistress effects of BZDs by using diazepam and chlordiazepoxide as representative drugs. A single dose of diazepam (5 mg/kg, i.p.) or chlordiazepoxide (20 mg/kg, i.p.) produced a significant reduction in locomotor activity, a measure of sedative effect and antagonized the effect of restraint stress (RS) on gastric mucosal lesions and anti-sheep red blood cell (SRBC) antibody titre. With chronic treatment (X 7 d), there was a marked tolerance to the sedative effect of both the studied BZD drugs, while much less tolerance developed to their ulcer protective action. However, no tolerance was observed to the attenuating effect of diazepam and chlordiazepoxide on RS-induced immunosuppression. Thus, the results of the present study indicate that different mechanisms may be involved in the development of tolerance to the sedative, antiulcer and immunomodulatory effects of BZDs. PMID- 11211565 TI - Relevance of serum alkaline phosphatase as a diagnostic aid in lung pathology. PMID- 11211566 TI - Anaerobic power and cardiorespiratory evaluation in untrained males (18-19 years). PMID- 11211567 TI - Endogenous depression, thyroid function and acupuncture. PMID- 11211568 TI - Effect of glibenclamide in gabapentin antinociception. PMID- 11211569 TI - An overview of pathophysiology and treatment of insulin resistance. AB - Insulin resistance has emerged out as a concept linking diabetes mellitus and hypertension. Clinically it is characterized by hyperinsulinemia, hypertension, central obesity, abnormal lipid profile and cardiovascular complications. Insulin resistance is often associated with presence of anti-insulin antibodies and absent or dysfunctional insulin receptors. At molecular level insulin resistance appears to occur at the level of G-protein, kinase activation, glucose carriers (GLUT) and gene expression. Although with advent or research, the molecular mechanisms of insulin resistance are becoming more clear and there is development of new therapeutic agents like insulin sensitizers (thizolidinediones), in clinical practice, as of today, a patient with insulin resistance is looked upon as hypertensive or having diabetes mellitus. Accordingly he is taking either antihypertensives or antidiabetic drugs or both. It is thus essential to look into effects of these agents on insulin sensitivity. In recent years some scattered studies have been conducted to evaluate the effect of various antihypertensives and antidiabetics on insulin sensitivity. An antihypertensive or antidiabetic drug should directly benefit the cardiovascular risk profile of these patients. Although various newer approaches are explored to have a therapeutic benefit in insulin resistance, it is still a long way in the research, when a suitable pharmacological agent with least untoward effects will be available for the treatment of insulin residence. PMID- 11211570 TI - Effect of yogic exercises on physical and mental health of young fellowship course trainees. AB - A study was undertaken to observe any beneficial effect of yogic practices during training period on the young trainees. 54 trainees of 20-25 years age group were divided randomly in two groups i.e. yoga and control group. Yoga group (23 males and 5 females) was administered yogic practices for the first five months of the course while control group (21 males and 5 females) did not perform yogic exercises during this period. From the 6th to 10th month of training both the groups performed the yogic practices. Physiological parameters like heart rate, blood pressure, oral temperature, skin temperature in resting condition, responses to maximal and submaximal exercise, body flexibility were recorded. Psychological parameters like personality, learning, arithmetic and psychomotor ability, mental well being were also recorded. Various parameters were taken before and during the 5th and 10th month of training period. Initially there was relatively higher sympathetic activity in both the groups due to the new work/training environment but gradually it subsided. Later on at the 5th and 10th month, yoga group had relatively lower sympathetic activity than the control group. There was improvement in performance at submaximal level of exercise and in anaerobic threshold in the yoga group. Shoulder, hip, trunk and neck flexibility improved in the yoga group. There was improvement in various psychological parameters like reduction in anxiety and depression and a better mental function after yogic practices. PMID- 11211571 TI - The effects of vasopressin in isolated rat hearts. AB - The roles of cGMP, prostaglandins, the entry of extracellular Ca2+ through slow channels, endothelium and V1 receptors in the negative inotropic, chronotropic and coronary vasoconstrictor responses to arginine vasopressin (AVP) have been investigated in isolated perfused rat hearts. The bolus injection of 5 x 10(-5) M AVP produced a significant decrease in contractile force, heart rate and coronary flow. AVP also significantly decreased contractile force, heart rate and coronary flow in hearts pretreated with an inhibitor of soluble guanylate cyclase methylene blue (10(-6) M), an effective drug for removing endothelium saponin (500 micrograms/ml), an inhibitor of cyclooxygenase indomethacin (10(-5) M) or a calcium channel antagonist verapamil (5 x 10(-7) M). The potent V1 receptor antagonist [Deamino-Pen1, Val4, D-Arg8]-vasopressin (9 x 10(-5) M) did not alter effects of AVP but the very potent V1 receptor antagonist [beta-Mercapto-beta, beta-cyclopentamethylene-propionyl1, O-Me-Tyr2, Arg8]-vasopressin (8 x 10(-5) M) abolished these effects. Our results suggest that AVP produces negative inotropic, chronotropic and coronary vasoconstrictor effects in isolated perfused rat hearts. cGMP, prostaglandin release and Ca2+ entry does not involve in the effects of AVP. These effects are endothelium independent and mediated by V1 receptors. The use of V1 receptor antagonist [beta-mercapto-beta, beta cyclopentamethylene-propionyl1, O-Me-Tyr2, Arg8]-vasopressin may be beneficial for preventing the negative inotropy, chronotropy and coronary vasoconstriction induced by AVP. PMID- 11211572 TI - Lateral difference in reaction times to lateralized auditory stimuli. AB - Evidence suggests that Reaction time (RT) is affected by human behaviour in that stimuli are processed and conducted faster and more accurately when they are presented directly to the specialised hemisphere and responded to more quickly when stimulus and response are mediated by the same hemisphere. The purpose of the current study was to investigate the effect of laterality using one parameter reaction time (RT) on ipsilateral reactions to monuaural latralized stimuli. Twenty-four undergraduate polytechnic students and 10 representative level Rugby players participated in the study by reacting unilaterally to single and choice RT using simple and complicated sensor motor reactions (SMR). Results Shorter reaction times by the dominant hand while testing simple and complicated audio SMR, without reference to sex and sport skills results have been explained in terms of specialisation of left hemisphere in different aspects of information processes mechanisms, geared towards programming of the movement. PMID- 11211573 TI - Research in reproduction: the Indian scenario in the last decade [II]. AB - Developing new, improved and totally safe, effective and acceptable contraceptives based on the recent advances in cellular and molecular biology of reproduction is a new challenge to biomedical scientists involved in research in reproductive biology. The present article reviews some of the major contributions made during the last decade by scientists working in India in developing new strategies and technologies for better human reproductive health and fertility regulation. PMID- 11211574 TI - Effect of Chyawanprash and vitamin C on glucose tolerance and lipoprotein profile. AB - Chyawanprash is an ancient Indian dietary supplement containing vitamin C (34 mg/100 g) derived from amla (Emblica officinalis). In addition, Chyawanprash also contains several other herbal products. The present study was designed to compare the effects of vitamin C with those of Chyawanprash. Ten normal healthy adult male volunteers (age 20-32 years) participated in the 16-week study. They were placed randomly in either the Chyawanprash group (n = 5) or vitamin C group (n = 5). Those in the former received 15 g/d of Chyawanprash while those in the latter received 500 mg/d vitamin C during the first 8 weeks of the study. For the next 8 weeks, no supplement was given. For each individual, an oral glucose tolerance test was performed, and lipoprotein profile in peripheral serum samples was determined at 0 weeks, 4 weeks, 8 weeks, 12 weeks and 16 weeks. In the Chyawanprash group, the 8 weeks Vs 0 weeks value (mean +/- S.D.) respectively for various indices which were significantly different were fasting plasma glucose (100.2 +/- 5.58 mg/dl vs 116.2 +/- 11.6 mg/dl), area under 2-h plasma glucose curve (245.9 +/- 15.13 mg.dl-1.h vs 280.8 +/- 37.09 mg.dl-1.h), HDL cholesterol (53.2 +/- 4.56 mg/dl vs 42.7 +/- 7.17 mg/dl), LDL cholesterol (82.4 +/- 8.80 mg/dl vs 98.26 +/- 12.07 mg/dl), LDL/HDL ratio (1.56 +/- 0.28 vs 2.38 +/- 0.63). In the Vitamin C group, only the LDL/HDL ratio was significantly lower at 8 weeks than at 0 weeks (1.99 +/- 0.44 vs 2.29 +/- 0.43). All the variables that changed significantly were no longer significantly different from the 0 weeks value at 16 weeks. Chyawanprash reduces postprandial glycemia in the oral glucose tolerance test and reduces blood cholesterol level to a significantly greater extent than vitamin C. PMID- 11211575 TI - Efficacy of naturopathy and yoga in bronchial asthma--a self controlled matched scientific study. AB - Asthma is one of the common psychosomatic illness influenced by many factors. Bronchodilators give temporary relief and have side effects. The present study is aimed at finding the efficacy of a non-pharmacological approach of naturopathy and Yoga in bronchial asthma. A total no of 37 patients (19 men, 18 women) with mean age 35.06 yrs (men), 40.74 yrs (women) admitted to INYS, Bangalore, for the period of 21 days. The treatment included 1. Diet therapy 2. Nature cure treatment and 3. Yoga therapy. The various parameters including lung function test were measured on admission and once a week. Results showed the significant improvement in PEFR, VC, FVC, FEV1, FEV/FEC %, MVV, ESR and absolute eosinophil count. The patients reported a feeling of well being, freshness and comfortable breathing. Naturopathy and yoga helps in inducing positive health, alleviating the symptoms of disease by acting at physical and mental levels. PMID- 11211576 TI - Induction of seminiferous tubular atrophy by single dose of 5-fluorouracil (5-FU) in Wistar rats. AB - Antimetabolite, 5-fluorouracil (5-FU) is known to cause testicular damage by epithelial sloughing and cell killing. However, it is not known whether 5-FU induces tubular atrophy and the fate of exfoliated germ cells. Present study was conducted to evaluate these effects of 5-FU on rat testis. Animals were injected, single dose of 5-FU (10.50 & 100 mg/kg, i.p.) and sampled at 1, 3, 15 and 30 day following the treatment. The testes were perfusion fixed by Bouin's fluid. Five micron thick paraffin sections of testes and epididymis were stained with haematoxylin and eosin. Slides were examined for the incidence of abnormal tubules (per 200 tubules), tubular diameter (STD), epithelial height (SEH) and for the presence of germ cells in the epididymis. Data were analysed by Mann Whitney 'U' test. The testes weight, STD, SEH were decreased (P < 0.05-0.01) in treated animals. The abnormal tubules were increased in a dose dependent manner with atrophic tubules seen on 30 d. The exfoliated germ cells have not blocked the post testicular ductal system and found in the epididymis in a dose dependent manner. The present study concludes that 5-FU causes tubular shrinkage and atrophy. Further, epididymis is involved in the phagocytosis of germ cells. PMID- 11211578 TI - Can we finally get it right with cancer pain control? PMID- 11211577 TI - Effect of systemically administered nitric oxide donor, sodium nitroprusside on picrotoxin-induced convulsions in rats. AB - Nitric oxide (NO), the gaseous neurotransmitter has been reported to have an endogenous anticonvulsant property. This has prompted proposals to develop NO donors as anticonvulsant drugs. In the present study, the effect of NO donor, sodium nitroprusside (SNP) on picrotoxin (PCT)-induced convulsions was investigated. A convulsant dose of PCT (5 mg/kg) was administered 5, 10, 15 and 30 min after intraperitoneal injection of graded doses (0.7, 1.25 and 2.5 mg/kg) of SNP. SNP at doses 0.7 and 1.25 mg/kg increased dose dependently the severity of PCT-induced convulsions. But, pretreatment with the higher dose (2.5 mg/kg) of SNP was protective against PCT-induced convulsions. However, post treatment (5 and 10 min) with the same dose exacerbated convulsions and caused death of the animals. These results indicate that the vasodilator effect of SNP and an increased perfusion of PCT into brain may be responsible for the proconvulsant action of SNP. A decreased entry of PCT because of marked vasodilation and hypotension has been speculated for an inhibition of convulsions in animals pretreated with a higher dose of SNP. In conclusion, the results reveal the non suitability of SNP to be developed as an anticonvulsant. PMID- 11211579 TI - The use of patient information leaflets in surgery. PMID- 11211580 TI - Islet cell tumours: diagnosis and medical management. AB - Islet cell tumours are difficult to diagnose. They are rare tumours that secrete hormones resulting in symptoms and signs that are often mistaken for more common conditions. Benign and solitary tumours are surgically resected, while medical therapy aims at symptom control and palliation of malignant disease. PMID- 11211581 TI - Islet cell tumours: surgical treatment. AB - The majority of neuroendocrine tumours of the pancreas are malignant and surgical resection is the mainstay of treatment. The tumours are often small and intraoperative tumour localization is an important part of the operation. The type of tumour will dictate specific treatment. PMID- 11211582 TI - Thyroid disease in pregnancy. AB - Some interesting recent developments have influenced the modern management of thyroid disease in pregnancy and enhanced our understanding of the interaction between maternal and fetal thyroid function, including the complex role of the placenta. This article will review the latest ideas in this area. PMID- 11211583 TI - Organizing the care of lung cancer patients. AB - For years lung cancer has been the Cinderella of malignant disease, perceived as being self-inflicted and incurable. The government has put cancer management high on its agenda and is setting targets for clinicians to aim at. This article looks at the changes which are occurring in the way lung cancer is managed. PMID- 11211584 TI - Managing patients with meconium-stained amniotic fluid. AB - Meconium-stained amniotic fluid might signify underlying acute or chronic fetal hypoxia with adverse perinatal outcome, especially if associated with cardiotocographic abnormality. Management requires awareness of this potential risk, appropriate intrapartum care and a combined obstetricneonatal approach. Amnioinfusion can be an effective preventative measure. PMID- 11211585 TI - Disulfiram revisited. AB - Disulfiram can be important in helping motivated alcoholics to remain abstinent. Prescribers should be aware of disulfiram's toxicity, and how to recognize and manage reactions. A number of other agents are available to help alcoholics remain sober, although these do not necessarily obviate use of disulfiram. Also, disulfiram may have a wider role in the management of the addictions, e.g. in cocaine use. PMID- 11211586 TI - Improving reporting of sharp injuries. AB - There is considerable under-reporting of contaminated needlestick and other sharp object injuries among health-care workers. Some general and psychological factors contribute to such low reporting. Continued training of staff, a sympathetic attitude and clarification of some general issues might improve reporting of such incidents. PMID- 11211587 TI - Spinal anaesthesia for caesarean section: current clinical practice. AB - Spinal anaesthesia has evolved as the preferred anaesthetic technique for most cases of caesarean section. Having been extensively studied and refined over the years, there are few situations where a spinal is absolutely contraindicated. While general anaesthesia will always have a place in obstetrics, in experienced hands a spinal offers safety, efficacy and an improvement in maternal morbidity. PMID- 11211588 TI - The effect of 1-year rotations on stress in preregistration house officers. AB - A comparison of stress levels in preregistration house officers demonstrated lower levels in those completing 1-year rotations compared with those completing 6-month posts in two different hospitals. One-year rotations provide a more stable environment, allow new doctors to become familiar with the workings of an organization from several viewpoints and permit a better sense of working within a multiprofessional team than the traditional arrangements. PMID- 11211589 TI - A mentorship scheme for senior house officers. AB - Many junior doctors are unsure as to how their aspirations and developing abilities will match up to the demands of specialty training. They need sensitive and realistic guidance if they are to make the right career choice in a highly competitive market. PMID- 11211590 TI - Writing a case report: an editor's eye view. AB - 'That was a nice presentation. Why not write it up for a journal?' With such words a thousand case reports are born. But they are like birds tossed over a stormy ocean: only a few gain a foothold in the rigging of passing ships--for the rest, oblivion. So, how do you persuade an editor to accept your wonderful case report? Here are some reflections from the editor's standpoint. PMID- 11211591 TI - Extrapancreatic tumour hypoglycaemia. PMID- 11211592 TI - Basilar artery aneurysm: an unusual cause of intractable hiccups. PMID- 11211593 TI - A triple dose of iron deficiency anaemia. PMID- 11211594 TI - Retrospective ethics: a block to progress? PMID- 11211595 TI - Use of patient information leaflets in surgery. PMID- 11211596 TI - Management of acute heart failure. PMID- 11211597 TI - Wisdom tooth extraction under general anaesthesia. PMID- 11211598 TI - Human rabies in Montreal, Quebec--October, 2000. PMID- 11211599 TI - Human rabies in Canada--1994-2000. PMID- 11211600 TI - Drinking water quality and health-care utilization for gastrointestinal illness in greater Vancouver. AB - The risk of microbial disease associated with drinking water is presently a priority concern among North American water jurisdictions. Numerous past outbreaks, together with recent studies suggesting that drinking water may be a substantial contributor to endemic (non-outbreak related) gastroenteritis, demonstrate the vulnerability of many North American cities to waterborne diseases and have fuelled ongoing debates in Canada and the United States concerning the need for stricter water quality guidelines, changes in watershed management policies, and the need for additional water treatment. The Greater Vancouver Regional District (GVRD) water supply system serves approximately two million consumers from a system consisting of three unfiltered surface water supplies (Figure 1). Although GVRD policies reduce the potential for fecal contamination of the source water supplies by humans and domestic animals, the GVRD watersheds support many wildlife species that can potentially shed organisms pathogenic to humans. Because GVRD's water treatment strategy relies principally on watershed protection and chlorination*, and these two strategies together do not eliminate all risk of waterborne disease transmission, it is possible that some disease-causing organisms reach the consumer. PMID- 11211601 TI - Update: West Nile Virus activity--eastern United States, 2000. PMID- 11211602 TI - Perspectives. States struggle to piece together puzzle of uninsured. PMID- 11211603 TI - Whither the atypical (dysplastic) nevus? PMID- 11211604 TI - Judging academic pathology chairpersons. PMID- 11211605 TI - Chairpersons of pathology in the United States. Benchmarks for academic publications and professional credentials. AB - Chairpersons of pathology often are viewed as departmental role models in academic medical centers. To objectify this view, we undertook a systematic survey of publication records and professional certification among 126 chairpersons in the United States. The median of the total number of scientific publications by the cohort was 105 since graduation from medical school, and the median yearly number of peer-reviewed papers was 3.34 per person (mean, 4.25). A random 10% of the study population was analyzed further with reference to the percentage of publications that reflected basic science research; 41% of the total literature contributions of this subgroup fit that description, and only 38% of the chairpersons in the subgroup had 80% or more non-service-related publications. Of all chairpersons, 85% had obtained primary board certification in anatomic pathology, clinical pathology, or both, and 25% of the group had earned at least 1 subspecialty board certificate in addition. These numbers reflect an evolution in the professional backgrounds of chairpersons of pathology such that demands for academic scholarship and proficiency in hospital practice and management seem to pertain to that group. PMID- 11211606 TI - To IRB or not to IRB? That is no longer the question. PMID- 11211607 TI - Critical analysis of histologic criteria for grading atypical (dysplastic) melanocytic nevi. AB - Low concordance in grading atypical (dysplastic) melanocytic nevi (AMN) has been reported, and no systematic evaluation is available. We studied 123 AMN with architectural and cytologic atypia (40 associated with atypical-mole syndrome), classified according to standard criteria by 3 independent observers. Histologic variables included junctional and dermal symmetry, lateral extension, cohesion and migration of epidermal melanocytes, maturation, regression, nuclear features, nuclear grade, melanin, inflammatory infiltrate location, and fibroplasia. AMN (43 junctional and 80 compound) were graded mild (31), moderate (61), and severe (31). AMN-severe correlated with 3 or more nuclear abnormalities (especially pleomorphism, heterogeneous chromatin, and prominent nucleolus) and absence of regression, mixed junctional pattern, and suprabasilar melanocytes on top of lentiginous hyperplasia. AMN-severe diagnostic accuracy was 99.5% using these criteria, but only the absence of nuclear pleomorphism differentiated AMN-mild from AMN-moderate. No architectural features distinguishing AMN-mild from AMN moderate were selected as significant by the discriminant analysis. AMN from atypical-mole syndrome revealed subtle architectural differences, but none were statistically significant in the discriminant analysis. Histologic criteria can reliably distinguish AMN-severe but fail to differentiate AMN-mild from AMN moderate. AMN from atypical-mole syndrome cannot be diagnosed using pathologic criteria alone. PMID- 11211608 TI - Using a continuous transformation of the Breslow thickness for prognosis in cutaneous melanoma. AB - Although the Breslow thickness provides the most important histologic information for prognosis in cutaneous melanoma, controversies and uncertainty remain about how best to use thickness. It is unclear whether cut points should be used, or, if they are used, which are optimal. We studied new data collected from more than 1,000 patients followed up for a relatively long period. From Cox proportional hazards models of survival we learned that more cut points provide more prognostic information than using, for example, just 1 cut point at 1.7 mm. Nevertheless, a continuous transformation provides an effective alternative that captures the information that thickness provides, and it avoids the pitfalls of using multiple cut points. In a multivariate model, this transformation provided strong prognostic information, and the result produced a prognostic score for cutaneous melanoma. This score provides a practical way that Cox model results can be used, and we believe it consolidates the prognostic information provided by traditional histologic and clinical variables. When newer prognostic variables are introduced, we suggest that they be used with this continuous transformation of thickness rather than with cut points in thickness. PMID- 11211609 TI - PS6K amplification characterizes a small subset of anaplastic meningiomas. AB - PS6K, a putative oncogene mapped to chromosome 17q23, encodes a serine/threonine kinase, which phosphorylates ribosomal subunit 6 and is part of the insulin receptor signal transduction pathway involved in the regulation of messenger RNA translation, protein synthesis, cell cycle progression, and cell size. Comparative genomic hybridization studies have detected 17q23 amplifications in a subset of meningiomas, particularly those with aggressive histologic features. PS6K amplifications have been reported in breast cancer, another hormonally driven neoplasm. We assessed PS6K dosage in 94 archival paraffin-embedded meningiomas using dual-color fluorescence in situ hybridization. We found high level PS6K amplifications in 3 of 22 anaplastic grade III meningiomas. Amplification was confirmed by differential polymerase chain reaction in 1 of these cases. In contrast, no amplifications were identified in 37 benign (grade I) and 35 atypical (grade II) meningiomas. To our knowledge, this represents the first report of gene amplification in primary human meningiomas. Given its exclusive association with anaplastic meningiomas, PS6K amplification likely occurs during the malignant progression of a small subset of anaplastic tumors. Further studies are needed to map the 17q23 amplicon to determine whether additional genes in this region are amplified in high-grade meningiomas. PMID- 11211610 TI - Cellular dyscohesion in fine-needle aspiration of breast carcinoma. Prognostic indicator for axillary lymph node metastases? AB - The role of fine-needle aspiration (FNA) in the diagnosis of breast carcinoma is established. We evaluated whether the degree of cellular dyscohesion and the nuclear grade in FNA material of breast carcinomas are reliable prognostic predictors for ipsilateral axillary lymph node metastasis. FNA specimens from 98 women with infiltrating ductal and infiltrating lobular carcinomas were evaluated by 2 observers for degree of cellular dyscohesion and nuclear grade. Follow-up specimens from lumpectomy and/or mastectomy with axillary dissection were available for each patient. By univariate analysis, degree of cellular dyscohesion and nuclear grade were not predictive of axillary lymph node metastasis regardless of tumor size. High histologic grade, size greater than 2 cm, and patient age younger than 52 years were significant predictors of metastasis. By multivariate analysis, size greater than 2 cm and age younger than 52 years were statistically significant for lymph node metastasis. In contrast with a published study, the results of the present study fail to show cellular dyscohesion in FNA specimens as predictive of lymph node metastasis; however, the scoring method for determining the degree of cellular dyscohesion is reproducible between 2 independent observers. PMID- 11211611 TI - p53, but not c-Ki-ras, mutation and down-regulation of p21WAF1/CIP1 and cyclin D1 are associated with malignant transformation in gastric hyperplastic polyps. AB - To investigate tumorigenesis in the gastric hyperplastic polyp (HP), we evaluated 19 HPs with and 50 HPs without dysplasia (including carcinoma in situ), as compared with normal mucosa and fundic gland polyps. Helicobacter pylori density was highest in HPs without dysplasia. Apoptotic activity and Ki-67 and p53 expression also were higher in dysplasia in HPs than in normal mucosa, fundic gland polyps, or HPs themselves. The p21WAF1/CIP1 and cyclin D1 levels, in contrast, were highest in HPs. In HPs without dysplasia, size was correlated positively with the degree of stromal inflammation and with p53 and cyclin D1 expression. p53 and c-Ki-ras mutations were detected in 41% (8/19) and 5% (1/19) of dysplasia (including carcinoma in situ) in HPs. Our results demonstrate that the HP enlarges with enhanced cell turnover and overexpression of p53, p21WAF1/CIP1, and cyclin D1, associated with H pylori-related inflammation, and that p53 but not c-Ki-ras mutations may have an important role in dysplastic change in HPs. PMID- 11211612 TI - H-ras oncogene mutation in dedifferentiated liposarcoma. Polymerase chain reaction-restriction fragment length polymorphism analysis. AB - Point mutations of the ras gene family (K-ras, H-ras, and N-ras) are thought to be involved in the development of a variety of human tumors. Dedifferentiated liposarcoma is characterized by the coexistence of well-differentiated (WD) and high-grade anaplastic (HG) components. The presence of point mutations at codons 12 and 13 of the H-ras gene was studied in 34 liposarcomas, comprising 15 well differentiated liposarcomas and 19 dedifferentiated liposarcomas, and in 8 storiform-pleomorphic type malignant fibrous histiocytomas (MFHs) using polymerase chain reaction-restriction fragment length polymorphism and direct sequencing analysis. The 2 components of dedifferentiated liposarcoma were analyzed independently. H-ras mutations were seen only in dedifferentiated liposarcomas (4/19 [21%]), 1 in WD components and 3 in HG components. The mutation was not seen in any of 15 cases of well-differentiated liposarcoma. MFHs showed an H-ras mutation in 1 (12%) of 8 cases. Our results seem to suggest that the H-ras mutation is a relatively uncommon event in dedifferentiated liposarcoma, which may demonstrate an epiphenomenon of dedifferentiation in dedifferentiated liposarcoma. PMID- 11211613 TI - Sinonasal tract eosinophilic angiocentric fibrosis. A report of three cases. AB - Eosinophilic angiocentric fibrosis (EAF) is a rare submucosal fibrosis without a well-developed differential diagnosis. Three cases of sinonasal tract EAF were identified in 2 women and 1 man, aged 49, 64, and 28 years, respectively. The patients experienced a nasal cavity mass, maxillary pain, or nasal obstructive symptoms of long duration. The process involved the nasal septum (n = 2), nasal cavity (n = 1), and/or the maxillary sinus (n = 1). There was no evidence for Wegener granulomatosis, Churg-Strauss syndrome, Kimura disease, granuloma faciale, or erythema elevatum diutinum. Histologically, the lesions demonstrated a characteristic perivascular "onion-skin" fibrosis and a full spectrum of inflammatory cells, although eosinophils predominated. Necrosis and foreign body type giant cells were not identified. Surgical excision was used for all patients, who are all alive but with disease at last follow-up. Sinonasal tract EAF is a unique fibroproliferative disorder that does not seem to have systemic associations with known diseases. The characteristic histomorphologic features permit accurate diagnosis. PMID- 11211614 TI - Nonneoplastic endometrial signet-ring cells. Vacuolated decidual cells and stromal histiocytes mimicking adenocarcinoma. AB - We describe 5 patients (mean age, 50 years; all had uterine bleeding) whose routine endometrial biopsy and curettage specimens contained prominent signet ring cells. Each specimen contained loose aggregates of signet-ring cells scattered within the endometrial stroma that were characterized by peripherally displaced, small, uniform nuclei with indistinct nucleoli and showed no mitotic activity. The central portion of the cytoplasm was occupied by single or multiple cytoplasmic vacuoles. In all cases, the signet-ring cells were reactive for vimentin and negative for epithelial membrane antigen and cytokeratin. Four cases were focally positive for muscle-specific actin or smooth muscle actin and negative for CD68, Mac387, periodic acid-Schiff, mucicarmine, and alcian blue. In these 4 cases, the surrounding endometrial stroma showed decidual changes, and the signet-ring cells demonstrated a morphologic continuum with more typical decidualized stroma. As such, the signet-ring cells in these cases were vacuolated, decidualized endometrial stromal cells. In the remaining case, the vacuolar contents of the signet-ring cells were periodic acid-Schiff-positive and resistant to diastase predigestion, and the cells reacted with Mac387 and CD68. The surrounding stroma showed no decidual reaction. Thus, the signet-ring cells in this case were of histiocytic differentiation. Endometrial stroma occasionally may contain nonneoplastic signet-ring cells that closely mimic adenocarcinoma. At least 2 directions of differentiation, decidual and histiocytic, are possible. PMID- 11211615 TI - Diagnostic usefulness of CD23 and FMC-7 antigen expression patterns in B-cell lymphoma classification. AB - CD23 and FMC-7 are normal B-cell antigens used during diagnostic immunophenotyping of suspected lymphoproliferative disorders, but the diagnostic usefulness of antigenic expression patterns of simultaneous 2-color staining and flow cytometric analysis has not been reported. We evaluated the FMC-7 and CD23 expression pattern in 201 cases of B-cell lymphoma from tissue biopsy specimens by multiparameter flow cytometry. The CD23-/FMC-7+ pattern was the most common pattern in large cell, mantle cell, and marginal zone lymphomas. The CD23 and FMC 7 antigen, along with the CD5 coexpression pattern, permitted accurate classification of all 71 cases of small lymphocytic, mantle cell, and marginal zone types of lymphoma. The widest variation of patterns was with follicular cell lymphoma, although most cases expressed the CD23 +/-/FMC-7+ pattern (+/-, partial or minor subset expression). The CD23 and FMC-7 antigen expression pattern was predictive of subtypes in more than 95% of lymphoma cases and could narrow the differential diagnosis in the remaining cases. We conclude the flow cytometric CD23/FMC-7 expression pattern achieved by dual staining facilitates accurate and reproducible classification of B-cell lymphomas and has diagnostic usefulness. PMID- 11211617 TI - Comparison of four enzyme immunoassays with a western blot assay for the determination of type-specific antibodies to herpes simplex virus. AB - Most current enzyme immunoassays (EIAs) differentiate inadequately between types 1 and 2 herpes simplex virus (HSV) antibodies since significant cross-reactivity exists. We compared 4 IgG type-specific EIAs using a Western blot assay for resolution of discrepant results. The Diamedix had sensitivities of 100% for types 1 and 2 but specificities of only 71% and 61%, respectively. The cross reactivity rate was 82% in positive samples tested. For HSV types 1 and 2, the Zeus sensitivities were 92% and 98%, respectively; specificities were 72% and 79%, respectively; the cross-reactivity rate was 54%. For HSV types 1 and 2, the Wampole sensitivities were 98% and 95%, respectively; specificities were 68% and 85%, respectively; the cross-reactivity rate was 47%. For HSV types 1 and 2, the Meridian sensitivities were 98% and 90%, respectively; specificities were 96% and 100%, respectively; no cross-reactivity was found between positive samples tested. While the Diamedix, Zeus, and Wampole assays showed good sensitivity, they lacked type specificity. The Meridian EIA offers the highest specificity along with no observed cross-reactivity. This EIA may be an easier, reliable alternative to Western blot for the determination of HSV type-specific antibodies. PMID- 11211616 TI - Bone marrow involvement by nasal NK cell lymphoma at diagnosis is uncommon. AB - To look for subtle evidence of marrow involvement in nasal NK cell lymphoma at diagnosis, we retrospectively studied trephine biopsy specimens from 25 consecutive patients by 2 sensitive techniques: CD56 immunohistochemistry and Epstein-Barr virus-encoded RNA in situ hybridization (EBER ISH). Only 2 patients had marrow involvement by NK cell lymphoma at diagnosis. In 3 additional patients, marrow involvement developed during or after systemic recurrence. All 5 positive cases were revealed by EBER ISH, but only 3 cases showed CD56 immunoreactivity. Among the 5 cases, only 2 were recognized by morphologic assessment. All 5 patients died, often within a short period, compared with a mortality of 50% for patients without demonstrable marrow involvement. Marrow involvement is distinctly uncommon in nasal NK cell lymphoma at diagnosis, and EBER ISH is the most sensitive technique for the demonstration of occult NK cell lymphoma. Despite the low frequency of marrow involvement in nasal NK cell lymphoma, EBER ISH is worthwhile to identify the minor subgroup of patients with a high likelihood of early death due to disease and when autologous bone marrow or peripheral blood stem cell transplantation is contemplated. PMID- 11211618 TI - Prothrombin measurement using a patient self-testing system. Oral Anticoagulation Monitoring Study Group. AB - We enrolled 82 patients receiving oral anticoagulation in a pilot trial of a point-of-care (POC) prothrombin time (PT) device in a patient self-testing (PST) application in 7 US and Canadian hospital-based anticoagulation centers. The properly selected and suitably trained patients were given the PT device to test at home for 6 weeks. Patients returned within 3 hours of the self-test to the hospital clinic where a repeated test was performed by a health care professional using the patient's POC device (clinic). Blood specimens were obtained for routine laboratory PT determinations by the local hospital laboratory (hospital) and a reference laboratory. International Normalized Ratio agreement between the home test and the clinic test was excellent. Home results correlated well with reference laboratory results. Using the reference laboratory as a standard, 68% of hospital and 66% of home results matched the patient's therapeutic range classification of the reference laboratory result. Participants overwhelmingly reported satisfaction and willingness to perform the self-test. Our results confirm the equivalence of the PST PT and a reference laboratory result and suggest that PST PT technology is an appropriate and useful adjunct to routine oral anticoagulation monitoring methods. PMID- 11211619 TI - Point-of-care prothrombin time measurement for professional and patient self testing use. A multicenter clinical experience. Oral Anticoagulation Monitoring Study Group. AB - We enrolled 386 subjects in a multicenter study of a point-of-care (POC) prothrombin time (PT) testing device. POC tests were performed by health care professionals using venous and finger-stick specimens and by patients using finger-stick specimens. Venous blood also was analyzed in the local hospital laboratory and a national reference laboratory. Accurate POC results were obtained by professionals using both types of specimens. Patients' results were equivalent to those of professionals. The identification of the patient's therapeutic status based on the International Normalized Ratio (INR) was equivalent for POC and local hospital laboratory PT results; 75% of local laboratory results and 77% of POC results were within 0.4 INR of reference laboratory results, while 93% of either system (POC or local laboratory) were within 0.7 INR. Patients overwhelmingly reported satisfaction with the self-test, including the finger stick and device operation. The INR from the POC device is clinically equivalent to the laboratory INR for assessment of anticoagulation status and management decisions in professional and self-testing environments. Patients can learn to perform accurate PT testing, and POC PT testing is feasible in patients' homes. PMID- 11211620 TI - Apolipoprotein A-I-derived amyloid in atherosclerosis. Its association with plasma levels of apolipoprotein A-I and cholesterol. AB - Wild-type apolipoprotein A-I (apo A-I)-derived amyloid commonly occurs in atherosclerotic plaques. To clarify apo A-I amyloid formation, plasma levels of apo A-I and cholesterol were related to the presence of amyloid in atherosclerotic plaques in 15 patients with peripheral atherosclerosis, subjected to arterial reconstruction. Plasma levels of apo A-I and high-density lipoprotein (HDL) cholesterol were slightly higher in patients with apo A-I-derived amyloid than in those without, but the difference was not significant. Levels of low density lipoprotein cholesterol and total cholesterol were significantly higher in the group with amyloid. High concentrations of apo A-I in the arterial intima are probably of greater importance to amyloid formation than high plasma levels of the protein. During atherosclerosis, the acute phase reactant serum amyloid A may displace apo A-I from HDL, leading to increased concentration of lipid-free apo A-I in the intima and conformational changes of apo A-I, which make it more fibrillogenic. Some forms of amyloid fibrils have been shown to be cytotoxic. Apo A-I-derived amyloid is possibly a pathogenically important factor in atherosclerosis. PMID- 11211621 TI - Influence of sodium intake on the reliability of active renin as a measure of the renin-angiotensin system in essential hypertension. AB - Plasma renin activity (PRA), active renin (AR), prorenin, and angiotensinogen were assessed in 486 hypertensive and 175 normotensive subjects with a sodium intake of 10 or 200 mEq/d during supine and upright posture and after infusion of angiotensin II. PRA and AR levels were compared in hypertensive subjects in each condition. With low sodium intake, particularly while upright, there was a significant correlation between PRA and AR. In upright subjects with low sodium intake who had a PRA of 2.4 ng/mL per hour or less (1.85 nmol.L-1.h-1 or less), the correlation was also strong. With high sodium intake, the correlation was weaker. With intermediate sodium excretion, the correlation was intermediate. Prorenin was less predictive of PRA than was AR, and angiotensinogen had a marginal role. Using PRA during sodium restriction while upright as the standard for determining renin status, the precision of AR for predicting renin status was excellent. AR may be used for surrogate assessment of the renin-angiotensin system activity when the system is activated. PMID- 11211622 TI - Second opinions in diagnostic anatomic pathology. PMID- 11211623 TI - Urinalysis and urine culture. PMID- 11211624 TI - Why we need an international agreement on tobacco control. PMID- 11211625 TI - Editors' note: the power of pictures. PMID- 11211626 TI - The "truth" Tobacco Memorial. PMID- 11211627 TI - Cigarettes and the US Public Health Service in the 1950s. AB - The conclusion of the United States Surgeon General's Advisory Committee on Smoking and Health in 1964 that excessive cigarette smoking causes lung cancer is cited as the major turning point for public health action against cigarettes. But the surgeon general and US Public Health Service (PHS) scientists had concluded as early as 1957 that smoking was a cause of lung cancer, indeed, "the principal etiologic factor in the increased incidence of lung cancer." Throughout the 1950s, however, the PHS rejected further tobacco-related public health actions, such as placing warning labels on cigarettes or creating educational programs for schools. Instead, the agency continued to gather information and provided occasional assessments of the evidence as it came available. It was not until pressure mounted from outside the PHS in the early 1960s that more substantive action was taken. Earlier action was not taken because of the way in which PHS scientists (particularly those within the National Institutes of Health) and administrators viewed their roles in relation to science and public health. PMID- 11211628 TI - Trends in cigarette smoking in 36 populations from the early 1980s to the mid 1990s: findings from the WHO MONICA Project. AB - OBJECTIVES: This report analyzes cigarette smoking over 10 years in populations in the World Health Organization (WHO) MONICA Project (to monitor trends and determinants of cardiovascular disease). METHODS: Over 300,000 randomly selected subjects aged 25 to 64 years participated in surveys conducted in geographically defined populations. RESULTS: For men, smoking prevalence decreased by more than 5% in 16 of the 36 study populations, remained static in most others, but increased in Beijing. Where prevalence decreased, this was largely due to higher proportions of never smokers in the younger age groups rather than to smokers quitting. Among women, smoking prevalence increased by more than 5% in 6 populations and decreased by more than 5% in 9 populations. For women, smoking tended to increase in populations with low prevalence and decrease in populations with higher prevalence; for men, the reverse pattern was observed. CONCLUSIONS: These data illustrate the evolution of the smoking epidemic in populations and provide the basis for targeted public health interventions to support the WHO priority for tobacco control. PMID- 11211630 TI - Variation in youthful risks of progression from alcohol and tobacco to marijuana and to hard drugs across generations. AB - OBJECTIVES: Much research has documented that youthful substance use typically follows a sequence starting with use of alcohol or tobacco or both and potentially proceeding to marijuana and then hard drug use. This study explicitly examined the probabilities of progression through each stage and their covariates. METHODS: A secondary analysis of data from the National Household Survey on Drug Abuse (1979-1997) was conducted with particular sensitivity to the nature of substance use progression, sampling procedures, and reliability of self report data. RESULTS: Progression to marijuana and hard drug use was uncommon among persons born before World War II. The stages phenomenon essentially emerged with the baby boom and rose to a peak among persons born around 1960. Subsequently, progression risks at each stage declined. Progression risks were also higher among younger initiators of alcohol, tobacco, or marijuana use. CONCLUSIONS: The recent increase in youthful marijuana use has been offset by lower rates of progression to hard drug use among youths born in the 1970s. Dire predictions of future hard drug abuse by youths who came of age in the 1990s may be greatly overstated. PMID- 11211629 TI - Ten-year changes in smoking among young adults: are racial differences explained by socioeconomic factors in the CARDIA study? AB - OBJECTIVES: This study investigated whether socioeconomic factors explain racial/ethnic differences in regular smoking initiation and cessation. METHODS: Data were derived from the CARDIA study, a cohort of 5115 healthy adults aged 18 to 30 years at baseline (1985-1986) and recruited from the populations of 4 US cities. Respondents were followed over 10 years. RESULTS: Among 3950 respondents reexamined in 1995-1996, 20% of Whites and 33% of African Americans were smokers, as compared with 25% and 32%, respectively, in 1985-1986. On average, African Americans were of lower socioeconomic status. Ten-year regular smoking initiation rates for African American women, White women, African American men, and White men were 7.1%, 3.5%, 13.2%, and 5.1%, respectively, and the corresponding cessation rates were 25%, 35.1%, 19.2%, and 31.3%. After adjustment for socioeconomic factors, most 95% confidence intervals of the odds ratios for regular smoking initiation and cessation in African Americans vs Whites included 1. CONCLUSIONS: Less beneficial 10-year changes in smoking were observed in African Americans, but socioeconomic factors explained most of the racial disparity. PMID- 11211631 TI - Influence of a counteradvertising media campaign on initiation of smoking: the Florida "truth" campaign. AB - OBJECTIVES: The purpose of this study was to assess the short-term effects of television advertisements from the Florida "truth" campaign on rates of smoking initiation. METHODS: A follow-up survey of young people aged 12 to 17 years (n = 1820) interviewed during the first 6 months of the advertising campaign was conducted. Logistic regression analyses were used to estimate the independent effects of the campaign on smoking initiation while other factors were controlled for. RESULTS: Youths scoring at intermediate and high levels on a media effect index were less likely to initiate smoking than youths who could not confirm awareness of television advertisements. Adjusted odds ratios between the media index and measures of initiation were similar within categories of age, sex, susceptibility, and whether a parent smoked. CONCLUSIONS: Exposure to the "truth" media campaign lowered the risk of youth smoking initiation. However, the analysis did not demonstrate that all such media programs will be effective. PMID- 11211632 TI - Simulated effect of tobacco tax variation on population health in California. AB - OBJECTIVES: This study simulated the effects of tobacco excise tax increases on population health. METHODS: Five simulations were used to estimate health outcomes associated with tobacco tax policies: (1) the effects of price on smoking prevalence; (2) the effects of tobacco use on years of potential life lost; (3) the effect of tobacco use on quality of life (morbidity); (4) the integration of prevalence, mortality, and morbidity into a model of quality adjusted life years (QALYs); and (5) the development of confidence intervals around these estimates. Effects were estimated for 1 year after the tax's initiation and 75 years into the future. RESULTS: In California, a $0.50 tax increase and price elasticity of -0.40 would result in about 8389 QALYs (95% confidence interval [CI] = 4629, 12,113) saved the first year. Greater benefits would accrue each year until a steady state was reached after 75 years, when 52,136 QALYs (95% CI = 38,297, 66,262) would accrue each year. Higher taxes would produce even greater health benefits. CONCLUSIONS: A tobacco excise tax may be among a few policy options that will enhance a population's health status while making revenues available to government. PMID- 11211633 TI - The new battleground: California's experience with smoke-free bars. AB - OBJECTIVES: This study examined the tobacco industry's tactics in the political, grassroots, and media arenas in attempting to subvert California's smoke-free bar law, and the efforts of health advocates to uphold and promote the law by using the same 3 channels. METHODS: Interviews with key informants involved in the development and implementation of the smoke-free bar law were conducted. Information was gathered from bill analyses, internal memoranda, tobacco industry documents, media articles, and press releases. RESULTS: The tobacco industry worked both inside the legislature and through a public relations campaign to attempt to delay implementation of the law and to encourage noncompliance once the law was in effect. Health groups were able to uphold the law by framing the law as a health and worker safety issue. The health groups were less successful in pressing the state to implement the law. CONCLUSIONS: It is possible to enact and defend smoke-free bar laws, but doing so requires a substantial and sustained commitment by health advocates. The tobacco industry will fight this latest generation of clean indoor air laws even more aggressively than general workplace laws. PMID- 11211634 TI - Environmental tobacco smoke and periodontal disease in the United States. AB - OBJECTIVES: Cigarette smoking is a leading risk factor for periodontal disease. This cross-sectional study investigated the relation between environmental tobacco smoke (ETS) and periodontal disease in the United States. METHODS: Data were obtained from the Third National Health and Nutrition Examination Survey (1988-1994). The outcome was periodontal disease, defined as 1 or more periodontal sites with attachment loss of 3 mm or greater and a pocket depth of 4 mm or greater at the same site. Exposure to ETS at home and work was self reported. The study analyzed 6611 persons 18 years and older who had never smoked cigarettes or used other forms of tobacco. RESULTS: Exposure to ETS at home only, work only, and both was reported by 18.0%, 10.7%, and 3.8% of the study population, respectively. The adjusted odds of having periodontal disease were 1.6 (95% confidence interval = 1.1, 2.2) times greater for persons exposed to ETS than for persons not exposed. CONCLUSIONS: Among persons in the United States who had never used tobacco, those exposed to ETS were more likely to have periodontal disease than were those not exposed to ETS. PMID- 11211635 TI - Association of smoking with serum and dietary levels of antioxidants in adults: NHANES III, 1988-1994. AB - OBJECTIVES: This study examined the association of smoking with serum levels and dietary intakes of antioxidants in a nationally representative sample. METHODS: This study classified 7873 apparently healthy adults aged 17 to 50 years from National Health and Nutrition Examination Survey III (NHANES III) data as nonsmokers or as smokers if their serum cotinine levels were either lower than 14 ng/mL or 14 ng/mL or greater, respectively. SUDAAN software was used for the statistical analysis. RESULTS: Smokers of both sexes had significantly (P < .001) lower serum levels of vitamin C, alpha-carotene, beta-carotene, beta cryptoxanthin, and lutein/zeaxanthin. Reduction in the serum vitamin E, lycopene, and selenium levels in smokers was slight. Smokers also had significantly lower dietary intakes of vitamin C and beta-carotene. A significant (P < .001) inverse relation was found between serum vitamin C and beta-carotene levels and cotinine levels independent of diet effect, and a positive relation (P < .001) was found between serum levels and dietary intakes. CONCLUSIONS: Antioxidants appear to have differing declines in serum levels as a result of reduced dietary intakes and the effects of smoking. PMID- 11211636 TI - The impact of behavioral counseling on stage of change in fat intake, physical activity, and cigarette smoking in adults at increased risk of coronary heart disease. AB - OBJECTIVES: This study assessed stages of change in fat intake, physical activity, and cigarette smoking during a randomized controlled trial of behavioral counseling. METHODS: Twenty general practices (primary health care centers) were randomized to lifestyle counseling by behavioral methods or to usual health promotion. A total of 883 patients were selected for the presence of 1 or more of the following risk factors: cigarette smoking, high cholesterol, or a combination of a high body mass index and low physical activity. Stage of change (precontemplation, contemplation, preparation, and action/maintenance) was assessed at baseline and after 4 and 12 months. RESULTS: The odds of moving to action/maintenance for behavioral intervention vs control patients at 4 months were 2.15 (95% confidence interval [CI] = 1.30, 3.56) for fat reduction, 1.89 (95% CI = 1.07, 3.36) for increased physical activity, and 1.77 (95% CI = 0.76, 4.14) for smoking cessation. The likelihood of achieving action/maintenance was related to baseline stage for all 3 behaviors. CONCLUSIONS: Brief behavioral counseling based on advice matched to stage of readiness for change may be valuable in encouraging healthy lifestyles among patients in primary care at raised risk of cardiovascular disease. PMID- 11211637 TI - The benefits of interventions for work-related stress. AB - OBJECTIVES: This quantitative meta-analysis sought to determine the effectiveness of occupational stress-reducing interventions and the populations for which such interventions are most beneficial. METHODS: Forty-eight experimental studies (n = 3736) were included in the analysis. Four intervention types were distinguished: cognitive-behavioral interventions, relaxation techniques, multimodal programs, and organization-focused interventions. RESULTS: A small but significant overall effect was found. A moderate effect was found for cognitive-behavioral interventions and multimodal interventions, and a small effect was found for relaxation techniques. The effect size for organization-focused interventions was nonsignificant. Effects were most pronounced on the following outcome categories: complaints, psychologic resources and responses, and perceived quality of work life. CONCLUSIONS: Stress management interventions are effective. Cognitive behavioral interventions are more effective than the other intervention types. PMID- 11211638 TI - Do socioeconomic disadvantages persist into old age? Self-reported morbidity in a 29-year follow-up of the Whitehall Study. AB - OBJECTIVES: This study examined (1) the relation of employment grade in middle age to self-reported poor health and functional limitations in old age and (2) whether socioeconomic status at approximately the time of retirement modifies health differentials in old age. METHODS: Survivors of the Whitehall Study cohort of men were resurveyed. Respondents were aged 40 to 69 years when they were originally screened in 1967 to 1970. RESULTS: Compared with senior administrators, men in clerical or manual (low-grade) jobs in middle age had quadruple the odds of poor physical performance in old age, triple the odds of poor general health, and double the odds of poor mental health and disability. At most, 20% of these differences were explained by baseline health or risk factors. Men who moved from low to middle grades before retirement were less likely than those who remained in low grades to have poor mental health. CONCLUSIONS: Socioeconomic status in middle age and at approximately retirement age is associated with morbidity in old age. PMID- 11211639 TI - Smoking during pregnancy in Finland: determinants and trends, 1987-1997. AB - OBJECTIVES: This study examined determinants of and trends in smoking during pregnancy in Finland from 1987 through 1997. METHODS: A repeated cross-sectional investigation of 694,926 women was conducted. RESULTS: The prevalence of smoking during pregnancy remained similar from 1987 through 1997 (at 15%). In 1997, prevalences of smoking were alarmingly high among young (37%), single (30%), and less educated (25%) women and among women living in northern (20%) and eastern (19%) Finland. These determinants were persistent over time, with the exception of an increase in regional differences. CONCLUSIONS: Despite increasing knowledge of adverse effects, smoking during pregnancy has not declined in Finland over the past decade. PMID- 11211640 TI - Exposure of adolescent girls to cigar images in women's magazines, 1992-1998. AB - OBJECTIVES: This study assessed the exposure of adolescent girls to cigar images in women's magazines from 1992 to 1998. METHODS: Data were obtained from the 5 women's magazines with the highest readership of adolescent girls. RESULTS: We found a significant upward trend in cigar images portrayed in women's magazines and a significant increase in the portrayal of women cigar smokers over the period observed. Cigar images were less likely than cigarette images to promote tobacco or nontobacco products. Among advertisements, nearly all those that featured cigars promoted nontobacco products; advertisements featuring cigarettes overwhelmingly promoted tobacco products. CONCLUSIONS: Between 1992 and 1998, adolescent readers of women's magazines were increasingly exposed to images of cigars. PMID- 11211641 TI - The cigar revival and the popular press: a content analysis, 1987-1997. AB - OBJECTIVES: The purpose of this study was to examine print media coverage of cigars during the period 1987 to 1997. METHODS: A content analysis of 790 cigar focused newspaper and magazine articles was conducted. RESULTS: Cigar-focused articles increased substantially over the study period, paralleling increased cigar consumption. Articles focused on cigar business (39%) and events (19%). Only 4% of articles focused on health effects. Sixty-two percent portrayed cigars favorably. The tobacco industry was mentioned in 54% of articles and portrayed positively in 78%. Forty-two percent of the individuals quoted or described in articles were affiliated with the tobacco industry; only 5% were government/public health figures. CONCLUSIONS: Print coverage of cigars failed to communicate health risk messages and contributed to positive images of cigars. PMID- 11211642 TI - Television campaigns and adolescent marijuana use: tests of sensation seeking targeting. AB - OBJECTIVES: This study evaluated the effectiveness of targeted televised public service announcement campaigns in reducing marijuana use among high-sensation seeking adolescents. METHODS: The study used a controlled interrupted time-series design in 2 matched communities. Two televised antimarijuana campaigns were conducted in 1 county and 1 campaign in the comparison community. Personal interviews were conducted with 100 randomly selected teenagers monthly in each county for 32 months. RESULTS: All 3 campaigns reversed upward developmental trends in 30-day marijuana use among high-sensation seekers (P < .002). As expected, low-sensation seekers had low use levels, and no campaign effects were evident. CONCLUSIONS: Televised campaigns with high reach and frequency that use public service announcements designed for and targeted at high-sensation-seeking adolescents can significantly reduce substance use in this high-risk population. PMID- 11211643 TI - Tobacco use and quit attempts among methadone maintenance clients. AB - OBJECTIVES: This study examined tobacco use prevalence, types of tobacco used, interest in quitting, and prior quit attempts among persons in methadone maintenance treatment. METHODS: Counselors collected surveys from 84% (550 of 655) of all clients in a 4-county metropolitan area. RESULTS: Most clients (77%) smoked cigarettes. Of the 59 former tobacco users, only 6 reported using a cessation pharmacotherapy to quit. Three quarters of the current smokers had attempted to quit at least once, with an average of 5 attempts. Most smokers (80%) were "somewhat" or "very" interested in quitting. CONCLUSIONS: The quit ratio among methadone maintenance treatment clients was 12%, compared with 50% nationwide. To reduce morbidity and mortality, cessation interventions must be developed and disseminated. PMID- 11211644 TI - Support for smoke-free restaurants among Massachusetts adults, 1992-1999. AB - OBJECTIVES: The authors examined trends and predictors of public support for smoke-free restaurants in Massachusetts. METHODS: Since 1992, the Massachusetts Behavioral Risk Factor Surveillance System has asked survey respondents about their attitudes toward smoking in restaurants. Analyses using data from 1992 to 1999 characterized changes over time in support for smoke-free restaurants and the role of demographic and smoking-related factors in predicting support. RESULTS: During 1992 to 1999, the rate of support for smoke-free restaurants increased from 37.5% to 59.8%, with similar increases among current, former, and never smokers. After adjustment for smoking status, support was associated with socioeconomic characteristics, race/ethnicity, and household smoking rules. Among current smokers, lighter smokers and those who were trying to quit were more likely to endorse smoke-free restaurants. CONCLUSIONS: There has been a substantial increase in support for smoke-free restaurants among both smokers and nonsmokers in Massachusetts. PMID- 11211646 TI - Intention to use the female condom following a mass-marketing campaign in Lusaka, Zambia. AB - OBJECTIVES: This report examines intention to use the female condom among men and women in Lusaka, Zambia, who were exposed to mass-marketing of the female condom. METHODS: The study used data from a representative sample of consumers at outlets that sell or distribute the female condom and the male condom. RESULTS: In spite of a high level of awareness of the female condom, use of this method in the last year was considerably lower than use of the male condom. Intention to use the female condom in the future was highest among respondents who had used only the female condom in the last year. CONCLUSIONS: The female condom is likely to be most important for persons who are unable or unwilling to use the male condom. PMID- 11211645 TI - Maternal smoking and the risk of early weaning: a meta-analysis. AB - OBJECTIVES: This study reviewed evidence on the effect of maternal smoking on early weaning. METHODS: The following databases and journals were searched: Medline, Scientific Citation Index, Pediatrics, Journal of Pediatrics, New England Journal of Medicine, and Lancet. Analysis was restricted to studies in which infants who had never been breastfed were excluded or the prevalence of breastfeeding initiation was more than 90%. RESULTS: In smoking vs nonsmoking mothers, the random effects odds ratio for weaning before 3 months was 1.93 (95% confidence interval [CI] = 1.55, 2.40). An adjusted odds ratio of 1.50 (95% CI = 1.34, 1.68) was shown in studies that had lost-to-follow-up rates below 15% and included adequate adjustment for confounding. CONCLUSIONS: Maternal smoking increases the risk of early weaning. PMID- 11211647 TI - Where children sit in cars: the impact of Rhode Island's new legislation. AB - OBJECTIVES: This study evaluated the impact of Rhode Island's legislation requiring children younger than 6 years to sit in the rear of motor vehicles. METHODS: Roadside observations were conducted in Rhode Island and Massachusetts in 1997 and 1998. Multivariate regression was used to evaluate the proportion of vehicles carrying a child in the front seat. RESULTS: Data were collected on 3226 vehicles carrying at least 1 child. In 1998, Rhode Island vehicles were less likely to have a child in the front seat than in 1997 (odds ratio = 0.6; 95% confidence interval = 0.5, 0.7), whereas no significant changes in child passenger seating behavior occurred in Massachusetts during that period. CONCLUSIONS: Rhode Island's legislation seems to have promoted safer child passenger seating behavior. PMID- 11211648 TI - Importance of attributable risk in monitoring adverse events after immunization: hepatitis B vaccination in children. AB - OBJECTIVES: Most vaccine safety data present only the postvaccination incidence of all adverse events rather than an estimate of attributable risk. This study sought to illustrate the difference between the 2 estimates with data from a hepatitis B immunization program. METHODS: The incidence of health problems occurring before and after each dose of hepatitis B vaccine in a cohort of 1130 children were compared. RESULTS: Although 47.5% of all children reported an adverse event during the 4 weeks following each of the 3 doses, adverse events attributable to immunization occurred in only 10.6% of children. CONCLUSIONS: Postimmunization incidence systematically overestimates the risk of adverse events. Estimating actual attributable risk is necessary to avoid false beliefs regarding immunization. PMID- 11211649 TI - When is a cigar not a cigar? African American youths' understanding of "cigar" use. PMID- 11211650 TI - Diabetes care in community health centers: a reasonable standard of comparison? PMID- 11211651 TI - Improving diabetes care in community health centers. PMID- 11211652 TI - Does a fifth mechanism exist to explain lightning injuries? PMID- 11211653 TI - Money and medical science. PMID- 11211654 TI - Promises and challenges in tissue engineering. PMID- 11211655 TI - Contributions of the vacuum tube to early electrophysiological research. PMID- 11211656 TI - Human exposure to radio frequency and microwave radiation from portable and mobile telephones and other wireless communication devices--a COMAR technical information statement. PMID- 11211657 TI - Starting up an EMBS student branch. PMID- 11211658 TI - Automated control in biomedicine. PMID- 11211659 TI - Automated regulation of hemodynamic variables. PMID- 11211660 TI - Multitasked closed-loop control in anesthesia. PMID- 11211661 TI - The subcutaneous route to insulin-dependent diabetes therapy. PMID- 11211662 TI - The intravenous route to blood glucose control. PMID- 11211663 TI - Cloning biological synergies improves control of elbow neuroprosthesis. PMID- 11211665 TI - Robotic assistants aid surgeons during minimally invasive procedures. PMID- 11211666 TI - Repairing the damage. PMID- 11211664 TI - Surface-stimulation technology for grasping and walking neuroprosthesis. PMID- 11211667 TI - Pleistocene diets. Would we be healthier if we ate more like our ancient ancestors? What you need to know. PMID- 11211668 TI - ANAC's role in Cuba: what should it be? PMID- 11211669 TI - Correlates of sleep quality in persons with HIV disease. AB - This study used the Symptom Experience dimension of the revised UCSF Symptom Management Conceptual model to examine correlates of sleep quality in HIV infected persons. According to this model, person, health/illness, and environment categories influence perception of a symptom. The average person in the sample (N = 58) reported being HIV-infected for 8.5 years and was 46 years old, not working, and a person of color. Depending on the level of data, either chi square or Pearson correlations were computed between the person, health/illness, and environment categories and the dependent variable, sleep quality, as measured by the Pittsburgh Sleep Quality Index. Person variables significantly related to sleep quality were employment status, trait anxiety, and general well-being. Health/illness variables significantly related to sleep quality were length of time living with HIV disease and five health status measures (depressive symptoms, state anxiety, symptom severity, daytime sleepiness, and functional status). The environmental variables associated with sleep quality were sleeping alone, having a separate bedroom, and sleeping in a noisy room. Correlates of better sleep quality are positive general well-being, less anxious personality trait and emotional state, less daytime sleepiness, less depressive symptoms, and less symptom severity. Correlates of worse sleep quality are impaired functional status and longer duration of living with HIV disease. PMID- 11211670 TI - Effects of individualized acupuncture on sleep quality in HIV disease. AB - Although it may begin at any point, sleep disturbance often appears early in HIV disease and contributes to decreased quality of life during the course of the illness. Relatively few studies have explored the complex nature of poor sleep quality in HIV disease or tested interventions to improve sleep quality. The purpose of this study was threefold: explore the nature of sleep quality in HIV disease, test the relationship between pain and sleep quality, and test the effectiveness of acupuncture delivered in a group setting for improving sleep quality in those who are HIV infected. A pretest, posttest, preexperimental design was used to test the effects of acupuncture on sleep quality. Participating in the study were 21 HIV-infected men and women between the ages of 29 and 50 years who reported sleep disturbance three or more times per week and who scored greater than 5 on the Pittsburgh Sleep Quality Index. The Wrist Actigraph was used to measure sleep activity, and the Current Sleep Quality Index was used to measure sleep quality for 2 nights before and after a 5-week acupuncture intervention (10 treatments). Acupuncture was individualized to address insomnia and other symptoms reported by the participants. Sleep activity and sleep quality significantly improved following 5 weeks of individualized acupuncture delivered in a group setting. PMID- 11211671 TI - Mother-child interaction in the presence of maternal HIV infection. AB - This comparative study evaluated mother-child interaction in southeastern U.S. mother-child dyads where the mother was HIV positive and determined if the presence of maternal HIV infection was associated with differences in the quality of the mother-child interaction. A comparison was made between two groups of mother-child dyads, one where the mother was HIV positive (N = 25) and one where the mother was not HIV positive (N = 25). The Barnard model of mother-infant interaction guided this study. The quality of interaction within the dyads was assessed using the Nursing Child Assessment Teaching Scales (NCATS). Associated maternal, child, and environmental factors were described using an interview form, Centers for Epidemiologic Studies Depression Scale, and the Bayley Infant Neurodevelopmental Screener. The quality of mother-child interaction in the two groups was compared using chi square and paired t tests. Findings from this research showed no statistically significant difference in mother-child interaction (measured by NCATS) between the HIV-positive and HIV-negative groups. Although maternal symptoms of depression were noted in more of the HIV-positive mothers, covariant analysis failed to show this factor had any significant influence on mother-child interaction scores between the groups. It was noted that total sample (N = 50) group mean scores on NCATS maternal subscale and total interaction were significantly lower than published population norms. As the mother-child interaction has critical implications for the child, strategies to improve reciprocity need to be developed in this population, and attention must be paid to mental health needs of HIV-positive women. PMID- 11211672 TI - The status of HIV/AIDS nursing in Australia: a specialty in decline? AB - Since the introduction of highly active antiretroviral therapy (HAART), occasions of service for patients with HIV/AIDS have altered drastically. HIV/AIDS nurses perceived that this change in activity had caused an exodus from the specialty by experienced nurses, and those that remained were rapidly deskilling. A survey of nurses working in HIV/AIDS in Australia and New Zealand was conducted to assess the impact of HAART on nursing skills and retention. More than 72% of respondents reported that they had lost some or many clinical HIV/AIDS nursing skills. About 37% of nurses reported that they were losing confidence in their knowledge of the management of opportunistic infections and cancers. About 27% reported larger numbers of nurses leaving their specialty area than in previous years. To enable nurses to respond rapidly to a potential decline in the effectiveness of HAART, this loss in skills and knowledge must be addressed. PMID- 11211673 TI - Predictors of quality of life in AIDS patients. AB - BACKGROUND: While much work has been completed in relation to measuring and defining the varying dimensions of quality of life in HIV/AIDS, very little research attention has been directed toward identifying factors that influence or enhance quality of life. OBJECTIVE: This study examined whether variables relating to demographic characteristics, severity of illness, psychological status, or level of engagement in nursing care would predict quality of life in persons with advanced or late stage HIV/AIDS. METHODS: A convenience sample of 162 hospitalized male and female patients with AIDS participated in this study. The participants completed the HIV Symptom Checklist, the Beck Depression Inventory, the HIV-QAM (a measure of changes in the status of hospitalized AIDS patients due to nursing care), and two measures of engagement in nursing care. The Living With HIV Scale was used as the measure of quality of life. The two components of this scale were analyzed independently. RESULTS: The strongest predictor of decreased quality of life scores was depression (accounting for 23% of the variance), with symptoms accounting for 9.75% and female gender accounting for an additional 8%. Two measures of patient engagement with nursing care providers contributed a total of 13.44% of the variance in quality of life scores. CONCLUSIONS: The findings emphasize the importance of recognizing and treating depression in persons with HIV/AIDS. The number of symptoms and their frequency also has a profound effect on quality of life. Although modest, study findings suggest that quality of life for an acutely ill, hospitalized patient with AIDS is enhanced through more active involvement or engagement in the process of nursing care. PMID- 11211674 TI - AIDS, nursing, and physician-assisted suicide: Part 2. AB - Nurses who work in HIV/AIDS care often hold conflicting views from each other about appropriate nursing roles in relation to physician-assisted suicide. Regardless of whether the individual nurse supports or opposes physician-assisted suicide, nurses in HIV/AIDS care need to have a broad knowledge base of the legal and ethical issues related to physician-assisted suicide. This article has as its major purpose to provide nurses with the knowledge base they need to assist them in their work in clinical practice, education, policy development, and research. PMID- 11211676 TI - Landmark study on lipodystrophy demonstrates evolving perceptions by physicians who treat people living with HIV. PMID- 11211675 TI - Protection of human subjects: turbulent times. PMID- 11211677 TI - American International Health Alliance joins Medical Advocates for Social Justice to launch HIV/AIDS Russian language Internet partnership. PMID- 11211678 TI - The strain of cervical sprains. PMID- 11211679 TI - Words on standardized languages. PMID- 11211680 TI - Words on standardized languages. PMID- 11211681 TI - Words on standardized languages. PMID- 11211682 TI - Words on standardized languages. PMID- 11211684 TI - Election aftermath. How will the 2000 vote affect health care? PMID- 11211685 TI - 'It's not all in your head': irritable bowel syndrome. PMID- 11211686 TI - Emergency! Acute cholecystitis. PMID- 11211687 TI - Dysphagia: going down and staying down. PMID- 11211688 TI - Certified registered nurses: results of the Study of the Certified Workforce. PMID- 11211689 TI - Meperidine--a liability. PMID- 11211690 TI - Counting nurses: what is community health-public health nursing? PMID- 11211692 TI - Book of the Year Awards. The most valuable texts of 2000, as chosen by AJN's panel of judges. PMID- 11211691 TI - Rethinking the relationship between nursing and diversity. PMID- 11211693 TI - RN,C: what's in a letter? PMID- 11211694 TI - The journey of lifelong learning. PMID- 11211695 TI - You're not one of us. When discrimination based on national origin becomes a problem. PMID- 11211696 TI - Nursing comes to light. A tragedy and a film, both astonishing, illuminate our everyday heroes. PMID- 11211697 TI - Staffing: the ANA's primary concern. PMID- 11211698 TI - [Evaluation of antibiotic preparations for children from a standpoint of water solubilities]. AB - The evaluation of seven widely-used antibiotic preparations [five cephem antibiotics; cefaclor (CCL), cefpodoxime proxetil (CPDX-PR), cefdinir (CFDN), cefditoren pivoxil (CDTR-PI), cefcapene pivoxil (CFPN-PI), one macrolide; clarithromycin (CAM) and one penem; faropenem sodium (FRPM)] for children were performed from a standpoint of water-solubilities, both as a preparation and as a component drug. As the results, these preparations showed great differences in the water-solubilities when added 10 ml water to 0.5 g of each preparation. That is, their solubilities differed from about 40% (CFPN-PI) to 100% (FRPM) as a preparation, and from nearly 0% (CAM) to 100% (FRPM, CCL) as a component drug. Additionally, about a half of the insoluble residues were found to be the component drug, in the cases of three preparations (CPDX-PX, CFDN, CDTR-PI) which were solubilized at 80-90%. From these results, it was suggested that the marketed antibiotic preparations for children might be classified into three categories; i.e., [A] preparation for solution and suspension (FRPM, CCL), [B] preparation suitable to suspension (CPDX-PR, CFDN, CDTR-PI), and [C] fine granule preparation for children unsuitable to suspension (CFPN-PI, CAM). Consequently, the names for dosage-forms of these preparations should be standardized. PMID- 11211699 TI - [Clinical effects of cefoselis (CFSL) on infections in obstetric and gynecologic field and prevention of postoperative infections]. AB - Clinical effects of cefoselis (CFSL) on various infections and prevention of postoperative infections in the field of obstetrics and gynecology were investigated with a total of 100 patients of 8 facilities in Yamagata and the following results were obtained: 1. For the patients (n = 70) who received the treatment with CFSL at 2 g/day for 5 days to prevent postoperative infections, the treatment was effective for such infections in 68 of 69 (98.6%) except one to whom the treatment was discontinued during the course. 2. For the patients with infections (n = 30) who were treated with CFSL at 2-4 g/day for 5-7 days, the treatment was markedly effective in 8/30 (26.7%), effective in 21/30 (70%) and not effective in 1/30 (3.3%). The overall rate of efficacy was 29/30 (96.7%). Based on the clinical effects for each isolate, the bacteriological efficacy was evaluated as 29/29 and the rate of bacterial eradication for each isolate was 23/29 (79.3%). 3. Laboratory test revealed liver functional abnormalities in one patient and eruption, a subjective/objective symptom caused by CFSL was noted in two patients. These results suggest that CFSL is effective for various infections in obstetric and gynecologic field and also the prevention of postoperative infections. PMID- 11211700 TI - Food poisoning associated with the ingestion of fiddleheads--Quebec 1999. PMID- 11211701 TI - Waterborne outbreak of gastroenteritis associated with a contaminated municipal water supply, Walkerton, Ontario, May-June 2000. PMID- 11211702 TI - An outbreak of Salmonella enteritidis linked to baked goods from a local bakery in lower Mainland, British Columbia. PMID- 11211703 TI - Does smoking contribute to community acquired pneumonia? PMID- 11211704 TI - Are evaluation and research mutually exclusive for division of general practice? PMID- 11211705 TI - The clown doctors. AB - BACKGROUND: In 1996 The Humour Foundation was established in Australia, drawing on inspiration from the work of Patch Adams and the Clown Care Unit in New York. The mission statement of the Foundation is to introduce and promote the health benefits of humour to patients, their families and health care professionals. OBJECTIVE: To describe the work of the Clown Doctors in Australia and the role of humour in relieving suffering. DISCUSSION: Clown Doctor Units have been established at several major hospitals throughout Australia. They use performance skills, humour, empathy and sensitivity to support, nourish, divert and help patients (and staff) cope with difficult situations. PMID- 11211706 TI - Happiness and humour. A medical perspective. AB - BACKGROUND: The medical profession's focus on dealing with negative mental states has led to the suggestion of classifying 'happiness' as a major affective disorder (pleasant type). OBJECTIVE: To describe the symptoms and signs of happiness and discuss its health benefits. DISCUSSION: Epidemiological data suggests that happiness is related to personality factors such as high self esteem, feelings of personal control and extroversion and is unrelated to demographic factors or the ownership of consumer goods. Humour is a communication device specifically designed to elicit joy and happiness and is effective in relieving anxiety and stress and enhances communication in medical settings. Recapturing the optimistic enchantment with life that is a part of childhood may be a key to happiness and health. PMID- 11211707 TI - Finding your funny bone. Incorporating humour into medical practice. AB - BACKGROUND: Many people confuse seriousness with professionalism. Humour enables you to separate who you are from the difficult work you do. OBJECTIVE: To illustrate ways humour and fun can be incorporated into day to day working life. DISCUSSION: People are more productive, cooperative and flexible when they have fun at work. Becoming a humour consumer of tapes, jokes, TV shows, movies or funny books, strengthens your sense of humour, relieves stress and improves relationships. PMID- 11211708 TI - How humour keeps you well. AB - BACKGROUND: The beneficial effect of humour on health has long been recognised anecdotally and intuitively but studying and quantifying that effect is difficult. 'Studying humour is like dissecting a frog--you may know a lot but you end up with a dead frog.' (Mark Twain) OBJECTIVE: To describe some of the psychological and physiological effects of laughter and the health benefits of humour. DISCUSSION: Stress reduction has been shown to improve outcomes in the treatment of many health problems. While there are inherent difficulties in structuring studies to assess the impact of humour and laughter on health, positive psychological and physiological responses to laughter have been demonstrated in a variety of settings. In particular, laughter has a role in stress hormone reduction, improving mood, enhancing creativity, pain reduction, improving immunity and reducing blood pressure. PMID- 11211709 TI - Haemorrhoids. Essentials of clinical management. AB - BACKGROUND: Haemorrhoids are a frequent and familiar concern of patients in the GP surgery setting. OBJECTIVE: In this article, practical guidelines regarding the diagnosis and treatment of haemorrhoidal disease will be discussed. DISCUSSION: Careful diagnostic skills are required to recognise the differences between internal and external haemorrhoids and other significant anorectal pathology. With appropriate diagnosis, most haemorrhoids can be treated successfully nonsurgically in an office setting. PMID- 11211710 TI - Renal colic and recurrent urinary calculi. Management and prevention. AB - BACKGROUND: Urinary calculi are a relatively common problem and up to 80% of patients with calculi who are untreated will experience one or more recurrences within five years. OBJECTIVE: This paper outlines the causes of urinary calculi and presents evidence for the less conventional treatment of renal colic with NSAIDs such as intramuscular diclofenac in preference to traditional pethidine injections. The paper also deals with ways to prevent recurrence of stone formation. DISCUSSION: Effective treatment requires a clear understanding of the cause, and investigations need to be directed toward establishing this. Prevention is the cornerstone of management and requires patients to have a clear understanding of the problem. Follow up of these patients is essential. PMID- 11211711 TI - Intracavernosal injection therapy. Does it still have a role in erectile dysfunction? AB - BACKGROUND: Male erectile dysfunction (ED) is a common problem in the community. It may go unnoticed unless specific questions are asked. The range of management options has increased markedly over the past two decades. OBJECTIVE: This article revisits the option of intracavernosal injection therapy for male erectile dysfunction. DISCUSSION: Erectile dysfunction has attracted considerable interest and research. The recent availability of an orally effective medication (sildenafil) has brought about a paradigm shift in its management. PMID- 11211712 TI - The near fatal lick. PMID- 11211713 TI - The art of exchanging. PMID- 11211714 TI - The AFP tradition continues.... PMID- 11211715 TI - Practice tip. The pulley suture. PMID- 11211716 TI - Developing palliative care services in regional areas. The Ipswich Palliative Care Network model. AB - BACKGROUND: Although there are over 350 palliative care services present in Australia and New Zealand, the distribution of these is patchy. Patients in some regional and rural areas have little or no access to specialist services, and manage with the enthusiasm and general expertise of local practitioners. OBJECTIVE: This paper discusses the problems encountered in maintaining skills in palliative care in the face of small patient numbers and poor resources, and describes a solution that was developed in Ipswich, Queensland. DISCUSSION: The twin problem of GP skills maintenance and adequate community service provision in palliative care can be overcome by developing a general practice based service in conjunction with local health authorities and the community. Highlighting the benefits to the health authority and the community of maximal general practitioner involvement is the most important lever in securing cooperation. PMID- 11211718 TI - Enhanced primary care. Small step, giant change. PMID- 11211717 TI - The unkindness of cancers. Names change but the problem stays the same. PMID- 11211719 TI - Implementation of the enhanced primary care items requires ongoing education and evaluation. AB - OBJECTIVE: The study aimed to evaluate the uptake and usage of the Federal Government's Enhanced Primary Care (EPC) items by general practitioners in outer urban general practice. METHOD: Faxed questionnaire with telephone follow up of a random sample of 347 GPs in South West Sydney, in March and April 2000. RESULTS: There was a response rate of 70.6%. Seventy-three percent of respondents reported they had heard of the EPC package and 27% of all the respondents had used one or more of the items. Twenty-three percent had claimed for health assessments (median number 3), 4.5% for care plans (median number 3) and 4% for case conferences (median number 1). Just under half of the GPs who had claimed for health assessments had conducted them in the patient's home. Most GPs either had no system for the use of the items or planned to use them opportunistically. Forty-nine percent of GPs had an age-sex register and those who did were more likely to have claimed for an EPC item and to have specific plans for their use. CONCLUSION: While most GPs had heard of the EPC items, only a minority had used them and few planned to use them systematically within their practice. There is a need to address barriers to the uptake of the EPC items and to provide greater support to GPs and health professionals involved with their implementation, especially for care plans and case conferences. Evaluation of the EPC items needs to be an integral part of the implementation process. PMID- 11211720 TI - Care planning and case conferencing. Building effective multidisciplinary teams. AB - BACKGROUND: The new Medicare items that cover care plans and multidisciplinary case conferences for patients with complex and chronic medical conditions have introduced new challenges in primary health care. General practitioners may be required to develop new skills if they are to work effectively with other professionals and carers where health is not their only priority. OBJECTIVES: This paper reports briefly on findings from a particular research project into the key factors that contribute to effective multidisciplinary teams. Principles from this research that can be applied to GPs being involved in multidisciplinary care plans and case conferences will be examined. DISCUSSION: Key factors discussed include the importance of efficiency, flexibility, an holistic view of the patient, communication and personal and professional characteristics that contribute to a successful outcome in multidisciplinary patient care. PMID- 11211722 TI - 75+ health assessments. AB - BACKGROUND: The Enhanced Primary Care package (EPC) includes item numbers for annual health assessment of people aged 75 years and over. Nursing or allied health staff can perform these as home visits and save the general practitioner considerable time. OBJECTIVE: Explanatory notes for conducting these assessments are described with reference to the RACGP guidelines in print or on the internet. DISCUSSION: 75+ health assessments (75+ HA) represent an opportunity for GPs to improve the functional status of their elderly patients at the same time as building team work with nursing and allied health professionals. PMID- 11211721 TI - Colorectal cancer screening--what the guidelines don't tell you. PMID- 11211723 TI - Colorectal cancer in women--the need for prevention. PMID- 11211724 TI - Sustainable practice ... for men too. PMID- 11211725 TI - International law and global public health. PMID- 11211726 TI - [Spinocerebellar degeneration and Ca channel abnormality]. PMID- 11211727 TI - [Molecular and clinical features of SCA 7]. PMID- 11211728 TI - [Spinocerebellar ataxia type 8(SCA 8)]. PMID- 11211729 TI - [Molecular genetic analysis in the clinical neuro-oncology]. PMID- 11211730 TI - [Classification of spinocerebellar degeneration (SCD)]. PMID- 11211731 TI - Evaluation of distal and proximal axonal degeneration in patients with carpal tunnel syndrome. AB - In patients with carpal tunnel syndrome, varying degrees of demyelination and axonal degeneration occur in the median nerve. Only a few studies have examined axonal degeneration produced at proximal to the lesion. In this study proximal axonal degeneration was evaluated and compared with other parameters. In 40 consecutive CTS patient hands, distal latency (DL), compound muscle action potential amplitude (CMAP) and motor conduction velocity (MCV) were analyzed by conventional motor nerve conduction studies. Intrafascicular compound nerve action potential amplitude (N-CNAP) at the elbow after wrist simulation and its nerve conduction velocity (NCV) between wrist and elbow were also analyzed. The negative correlation of DL with CMAP was statistically significant (r = 0.577, p < 0.001). CMAP was correlated with either MCV (r = 0.537, p < 0.001) or N-CMAP (r = 0.710, p < 0.001). A significant correlation of MCV with NCV (r = 0.517, p < 0.001) was also indicated. There were no any other significant correlation among the parameters. In CTS the degree of demyelination and axonal degeneration influence the prognosis for nerve recovery after decompressive surgery. DL is mainly influenced by demyelination that results in conduction block and slowing at the carpal tunnel. CMAP and N-CNAP indicate the degree of axonal degeneration at distal and proximal to the compression site. As in electrophysiologic evaluation of mononeuropathies, proximal axonal degeneration is best assessed by both stimulation and recording electrode locationing proximal to the lesion. Recording of intrafascicular nerve action potential was a little invasive method, but it provided important informations. The negative correlation between DL and CMAP implies that distal axonal degeneration can occur in proportion to the conduction disturbance. Moreover, N-CNAP had a higher correlation with CMAP. The greater the distal axonal degeneration, the more the proximal axonal degeneration. Conduction velocity represents the velocity of the fastest conduction fiber, not the degree of axonal degeneration. PMID- 11211732 TI - [Hemorrhages of dorsal root ganglia and sensory disturbance in congenitally hydrocephalic HTX rats]. AB - Recently we reported the frequent occurrence of hemorrhages in the dorsal root ganglia of congenitally hydrocephalic HTX rats, an animal model of human congenital hydrocephalus. Therefore, we hypothesized that sensory disturbance might be present in these rats. In order to evaluate the sensory abnormality quantitatively, we injected 50 microliters of 5% formalin into the footpad of the left hind paw of hydrocephalic (n = 5) and non-hydrocephalic HTX rats (n = 5) and Wistar rats (n = 5) on postnatal days 17-23, and then recorded the licking response time for 60 min after injection. The mean licking time in the early (0 10 min) and late (10-60 min) phases was significantly longer in hydrocephalic HTX rats than in non-hydrocephalic HTX and Wistar rats (P < 0.05). Histologically, hemorrhages in the dorsal root ganglia were found in all five hydrocephalic animals, of which two had shown thalamic degeneration. These findings suggest that lesions in the dorsal root ganglia and thalamus may correspond to the sensory disturbance observed in congenitally hydrocephalic HTX rats. PMID- 11211733 TI - [Relationship between hyperglycemia following head injury and neurological outcome]. AB - Severe head injury is associated with a stress response that includes hyperglycemia, which has been shown in both experimental and clinical studies to exacerbate the severity of brain injury during ischemic conditions. To define the relationship between serum glucose levels and the outcome of patients suffering from closed head injury, we retrospectively reviewed the clinical courses of 88 consecutive head-injured patients. The patients were divided into two groups according to their GCS score on admission: severely head-injured group (GCS score of 8 or less) in 36 patients; moderately head-injured group (GCS score of 9 to 12) in 52 patients. Severely head-injured group had significantly higher serum glucose levels than moderately head-injured group (mean +/- standard error of the mean; 201 +/- 4.6 mg/dl vs. 171.4 +/- 3.8 mg/dl) (p < 0.01). Patients who subsequently resulted in severe disability, vegetative state, or death had significantly higher serum glucose levels than patients who had good recovery or moderate disability (204.9 +/- 5.9 mg/dl vs. 162.9 +/- 5.1 mg/dl) (p < 0.01). Cases with a fatal clinical course were mostly associated with high glucose levels. All patients who showed a serum glucose level greater than 240 mg/dl on admission were dead. These data suggest that the hyperglycemia on admission is a frequent component of the stress response to head injury, a significant indicator of severity of injury and a potent predictor of the outcome from head injury. PMID- 11211734 TI - [Unusual MR findings of Wernicke encephalopathy with cortical involvement]. AB - We report a 48-year-old chronic alcoholic man, who developed consciousness disturbance, oculomotor paresis, and flaccid tetraplegia. His dietary habit was very poor since one month prior to the present admission and he was drinking alcoholic beverage. On admission on April 19, 1999, he showed disturbance of consciousness, tetraparesis without sensory disturbance, gaze paresis, and vertical nystagmus on downward gaze. His blood thiamine level was 12 ng/ml (normal range: 23.8-45.9). MRI demonstrated symmetric hyperintense lesions in the motor and premotor cortices bilaterally, in addition to other changes indicating Wernicke's encephalopathy. His motor weakness and oculomotor disturbance improved after treatment with intravenous thiamine. His cortical MRI also normalized. We believe that his cortical abnormality was responsible for his motor paresis and this is an unusual and unique finding for Wernicke's encephalopathy. PMID- 11211735 TI - [Isolated abducens nerve palsy caused by the compression of the basilar artery: a case report]. AB - Several pathological etiologies are responsible for abducens nerve palsy, but a neuro-vascular compression of the basilar artery has rarely been recognized as one of the causes. We performed magnetic resonance imaging of the brainstem of 71 year-old female patient with left abducens nerve palsy using constructive interference in the steady state (CISS) method, which allowed high-resolution T 2 weighted imaging and detection of the artery and nerves as high and low intensity area respectively. MRI with CISS revealed the compression of the abducens nerve by the basilar artery at the root exit zone. During the first examination her systolic blood pressure was over 180 mmHg, so we prescribed hypotensive agents until it to normalized. Her symptom of abducens nerve palsy improved after a few days. It is conceivable that compression of the basilar artery may have caused isolated abducens nerve palsy as disclosed by MRI with CISS. PMID- 11211736 TI - [An operated case of bitemporal lobe epilepsy associated with old infarction in the left occipital lobe]. AB - A 15-year-old female, who presented with bitemporal lobe epilepsy associated with old infarction in the left occipital lobe, was reported. MRI with fluid attenuated inversion recovery sequence demonstrates cortical atrophy with hyperintensity of the white matter in the left occipital lobe as well as volume loss and hyperintensity of the left hippocampus. Interictal positron emission tomography with [18F]fluorodeoxy glucose (FDG-PET) and single photon emission computed tomography with technetium-99m-ethyl-cysteinate dimer indicate hypometabolism and hypoperfusion in the left occipital lobe and the left temporal lobe, respectively. Scalp recorded EEG did not lateralize the side of the epileptogenic zone. Chronic subdural electrode recording demonstrated that the ictal onset zones were located in the bilateral side of the temporal lobe. Eighty nine percent of 19 spontaneous seizures were left sided onset. The anterior temporal lobectomy with hippocampectomy was performed for the left side. Although temporal lobe epilepsy is sometimes a bilateral disease, unilateral lobectomy for a strong predominant side, based on the MRI and FDG-PET findings, is effective for some patients. PMID- 11211737 TI - [A case of cerebral venous thrombosis with reversible brain parenchymal lesions: usefulness of diffusion weighted imaging and measurement of apparent diffusion coefficient]. AB - A 47-year-old man with a history of thrombophlebitis of his left leg for several years presented with a mild left hemiparesis and ipsilateral hypesthesia. Magnetic resonance imaging showed subacute thrombosis of the superior sagittal sinus and a cortical vein of the right cerebral hemisphere. A linear hyperintense area was found in the white matter of the right postcentral gyrus on T 2- and diffusion weighted axial imagings on the 7 days after the onset. The patient was treated conservatively, and his clinical course was uneventful. His neurological dysfunctions recovered within approximately three weeks after the onset. The white matter lesion in the right postcentral gyrus also disappeared one month later. The apparent diffusion coefficients (ADCs) in the white matter of the pre- and postcentral gyrus were measured bilaterally on the ADC mapping imaging. In the subacute stage, the ADC values in the white matter of the right pre- and postcentral gyrus were 0.50 x 10(-3) mm2/sec and 0.91 x 10(-3) mm2/sec, respectively. The %ADC indicating the ratio of ADC value of the lesion to that of the contralateral brain tissue was calculated. The %ADCs in the white matter of the pre- and postcentral gyrus were 64.9% and 124.5% respectively. In the chronic stage, the ADC values in the white matter of the right pre- and postcentral gyrus were 0.96 x 10(-3) mm2/sec and 0.99 x 10(-3) mm2/sec, and the %ADCs improved to 106.7% and 106.5% respectively. The lesions in the white matter of the right pre- and postcentral gyrus were reversible. The former was thought to be mainly ascribed to cellular edema and the latter was vasogenic edema. The present case showed when %ADC of the ischemic lesion in cerebral venous thrombosis was higher than 60%-70%, conservative therapy alone is sufficient effective for the improvement of neurological deficits. PMID- 11211738 TI - [Tiny aneurysms of cortical arteries presenting as an acute subdural hematoma: a case report]. AB - A case of an acute subdural hematoma due to the rupture of a tiny aneurysm of a cortical artery is described. A 68-year-old man lightly hit the right side of his head. About 1 hour later, he became drowsy and exhibited moderate hemiparesis on the left side on admission. Computed tomographic scanning demonstrated an acute subdural hematoma on the right temporoparietal region. In the past, he had undergone the clipping of a non-ruptured aneurysm and a subdural-peritoneal shunt operation on the same side in another hospital. On surgical evacuation of the subdural hematoma, a pulsating bleeding from a ruptured tiny aneurysm of a cortical artery was observed. There were also some similar tiny aneurysms on other cortical arteries. A photograph of such a tiny aneurysm was first taken and presented. PMID- 11211739 TI - [Cerebral venous angioma with parenchymal high intensity on T 2-weighted images]. PMID- 11211740 TI - [Lipoma of the insula: MRI features]. PMID- 11211741 TI - [Adrenergic receptor and knockout mouse: 2). Alpha adrenergic receptor knockout mouse]. AB - The sympathetic nervous system regulates cardiovascular function by activating adrenergic receptors which are known to have a critical role in regulating transmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system. alpha 2A adrenergic receptor knockout mouse (alpha 2A-KO) showed an increase in sympathetic activity with resting tachycardia, depletion of cardiac tissue norepinephrine concentration. Knockout mouse study reveals that the alpha 2B adrenoceptor (alpha 2B AR) mediates the hypertensive response, and the alpha 2A AR mediates the hypotensive response, induced by alpha 2 agonists. Both the alpha 2A and alpha 2C AR subtypes are required for normal presynaptic control of transmitter release from sympathetic nerves. alpha 2A AR subtype inhibits transmitter release at high stimulation frequencies, whereas the alpha 2C AR subtype modulates neurotransmission at lower levels of nerve activity. Salt induced hypertension experiment using alpha 2B-KO and alpha 2C-KO revealed that alpha 2B AR subtype is necessary to raise BP in response to dietary salt loading. Lack of adequately functional renal alpha 2B AR is thought to preclude reabsorption of sodium. alpha 1B-KO study revealed that alpha 1B AR is a mediator of the blood pressure response and the aorta contractile response induced by alpha 1 agonists. PMID- 11211742 TI - [The effects of intravenous nicardipine on jugular venous oxygen saturation]. AB - We investigated the effects of intravenous nicardipine on jugular venous oxygen saturation (SjO2) in patients undergoing superficial temporal artery-middle cerebral artery anastomosis. Anesthesia was induced with intravenous thiamylal and fentanyl, and maintained by isoflurane and nitrous oxide in oxygen. In the presence of stable condition after the induction, nicardipine 0.5 microgram.kg 1.min-1 was administered intravenously for 180 minutes. Mean arterial pressure, heart rate, SjO2 and bladder temperature were recorded. Three hours after continuous infusion of nicardipine, plasma levels of nicardipine in artery and jugular vein were measured by liquid chromatography. The arterial concentration of nicardipine reached 23.9 +/- 8.06 ng.ml-1. The area under the curve between the arterial and jugular venous nicardipine during infusion was significantly different. Mean arterial pressure was reduced in response to administration of nicardipine. There were no significant changes in heart rate, bladder temperature and SjO2. We concluded that the current dose of nicardipine reached effective concentration for systemic hypotension without influencing SjO2. PMID- 11211743 TI - [Low concentration/high volume is more effective than high concentration/low volume for postoperative continuous epidural analgesia with the combination of bupivacaine and fentanyl]. AB - In 40 females undergoing gynecologic laparotomy, lumbar epidural analgesia using a disposable infusion pump was continued for postoperative 48 hours. Then the analgesic effect of epidural bupivacaine (4.8 mg.kg-1) plus fentanyl (12 micrograms.kg-1) diluted with normal saline was prospectively compared between the two groups; high concentration/low volume group (HC/LV, 96 ml of total volume and 2 ml.h-1 of infusion rate, n = 20) versus low concentration/high volume group (LC/HV, 240 ml of total volume and 5 ml.h-1 of infusion rate, n = 20). On postoperative day 1, LC/HV group showed the significantly lower visual analog scale and verbal pain score at rest than HC/LV group (P < 0.05). No significant differences in the incidence of side effects were observed between the groups. These results suggest that when the equivalent dose is given, the volume rather than the concentration of the solution is important for postoperative continuous epidural analgesia with the combination of bupivacaine and fentanyl. PMID- 11211744 TI - [A case of hyperperfusion syndrome treated successfully by propofol]. AB - Carotid endoarterectomy was performed for a 67-year-old male with severe stenosis in the right carotid artery under propofol-fentanyl anesthesia. After the surgery, blood pressure was controlled by sodium nitroprusside to maintain at the preoperative level. On the first postoperative day, he was alert and without neurological deficit, but he became restless with the left hemiparesis appearing on the next day. ECD-SPECT revealed hyperperfusion of the right hemisphere. Propofol was administered at the dose of 3-5 mg.kg-1.h-1 to normalize the perfusion. It appears that the cerebral blood flow was normalized. Hyperperfusion after carotid endoarterectomy can be controlled by propofol. PMID- 11211745 TI - [The influence of age on hemodynamics and the dose requirements of propofol and buprenorphine in total intravenous anesthesia]. AB - A retrospective study was performed to determine the influence of age on hemodynamics and awakening time in total intravenous anesthesia (TIVA) with propofol and buprenorphine for spinal surgery. Twenty patients (26-79 yr) were studied and allocated into following four groups by age: 26-49 yr, 50-59 yr, 60 69 yr, and elderly 70-79 yr. All patients were premedicated with midazolam (2.5-5 mg) i.m. Anesthesia was induced (60-180 ml.h-1) and maintained (20-60 ml.h-1) with propofol infusion with 40% oxygen in air, added with vecuronium and one single dose of buprenorphine (0.08-0.2 mg; 1.37-2.63 micrograms.kg-1) before incision. Mean arterial pressure was stable and did not differ in four groups. Heart rate was decreased (P < 0.01) in the elderly group compared with the group younger than 50 yr. Bradycardia (below 50 beat.min-1) occurred in 60% of the elderly group. An adequate dose of buprenorphine (microgram) was proposed as: 208 - 1.8 x age (yr) + 0.3 x weight (kg) (r = 0.90, P < 0.01). The induction and maintenance rates (ml.h-1) of propofol were decreased with age and increased with weight (P < 0.05). However, the maintenance dose of propofol (3.9-8.5 mg.kg-1.h 1) did not correlate with age. Awakening time was prolonged (P < 0.05) in the elderly group (17.0 +/- 7.2 min) as compared with the group of younger than 50 yr (8.0 +/- 3.9 min). The three patients requiring postoperative analgesics were younger than 60 yr. This study suggests that we should reduce the dose of buprenorphine with age in TIVA using propofol. About 50% of the dose given to the patient younger than 50 yr was considered adequate in the elderly group. PMID- 11211746 TI - [Anesthetic management for mitral valve replacement in a patient with idiopathic hypereosinophilic syndrome]. AB - We have experienced anesthetic management for mitral valve replacement in a 48 year-old female with idiopathic hypereosinophilic syndrome. Preoperative examination showed mild biventricular dysfunction. Anesthesia was induced and maintained with meticulous administration of fentanyl and midazolam in 66% oxygen. Administration of dopamine, dobutamine and prostaglandin E1 contributed to reducing afterload and maintaining cardiac output. The operative and postoperative courses were uneventful. Hypereosinophilic syndrome is one of the identified causes of restrictive cardiomyopathy. Anesthesia for patients with hypereosinophilic syndrome must be carried out carefully, because heart or respiratory failure is the most dangerous complication. In patients with hypereosinophilic syndrome requiring general anesthesia, perioperative steroid cover is advisable. This may reduce or prevent serious lung complications. PMID- 11211747 TI - [An immediately post-operative death of a patient undergoing right external carotid artery-posterior cerebral artery bypass]. AB - We experienced an immediately post-operative death due to rupture of a giant basilar aneurysm four hours after right external carotid artery-posterior cerebral artery bypass surgery. As we had had preanesthetic discussions with neurosurgeons repeatedly, they did not seek for a cause of the death on our anesthetic management. However, in general, not few surgeons believe that many postsurgical complications may be mainly due to anesthetic management but not to surgery as they believe that their surgical procedures are always faultless. Therefore, we should have a wealth of anesthetic knowledge to respond to any surgeon's questions regarding anesthetic management and to precisely explain a causal relation between postsurgical complications and anesthesia. In addition, we should have frequent discussions with surgeons on postsurgical management in sick patients. These may reduce misapprehensions of surgeons, patients and their family for anesthesia. PMID- 11211748 TI - [Anesthesia for emergency surgery in a patient with Shy-Drager syndrome]. AB - A 53-year-old man with Shy-Drager syndrome underwent emergency surgery for the resection of the larynx under general anesthesia. Anesthesia was induced with fentanyl 0.1 mg and thiopental 100 mg, and endotracheal intubation was facilitated with vecuronium 8 mg. The onset of action of vecuronium was very slow. Anesthesia was maintained with about 1% of sevoflurane, with nitrous oxide 3 l.min-1 in oxygen 3 l.min-1. Norepinephrine was effective for hypotension while dopamine was not. He was extubated on the first postoperative day without any complications. The effects of vecuronium, norepinephrine, and dopamine might be changed in the patient with Shy-Drager syndrome. PMID- 11211749 TI - [Pulmonary embolism during laparoscopic cholecystectomy detected by sudden decrease in end-tidal carbon dioxide pressure]. AB - We report a case of intraoperative pulmonary embolism, detected by a sudden decrease in end-tidal carbon dioxide pressure (PETCO2). The patient was a 56-year old female without any history of pulmonary disease. The patient was intubated and ventilated manually during the operation under anesthesia with sevoflurane, nitrous oxide, and vecuronium. The percutaneous oxygen saturation (SpO2) and PETCO2 were monitored continuously. Twenty minutes after starting the laparoscopic procedure, PETCO2 decreased suddenly from values between 34 and 38 mmHg to 24 mmHg, and SpO2 decreased from 99% to 95%. Nitrous oxide was discontinued. Removal of the drape revealed profound subcutaneous emphysema. Postoperative pulmonary scanning revealed areas with reduced pulmonary perfusion (Fig. 2). An intravenous bolus of heparin (3000 IU) was given immediately, followed by 10,000 IU heparin over the next 24 hours. The patient was discharged on the fifteenth postoperative day without any sequelae. Although monitoring pulmonary arterial pressure is generally considered a more reliable method for the early detection of pulmonary embolism, an invasive monitoring procedure, such as the insertion of a Swan-Ganz catheter, is usually not indicated in laparoscopic surgery. For the early detection of pulmonary embolism, we therefore recommend the continuous monitoring of PETCO2 during laparoscopic surgery. PMID- 11211750 TI - [Perioperative management of life-threatening intra-abdominal bleeding with intra aortic balloon occlusion catheter]. AB - Intra-thoracic aortic clamping using an intra-aortic balloon occlusion catheter (IABOC) is employed for patients with life-threatening intra-abdominal and/or extra-abdominal bleeding in spite of massive transfusion. For perioperative management, we inserted an IABOC preoperatively into a 59-year-old man with life threatening intra-abdominal bleeding from an abscess formed around his traumatically injured pancreas. We could perform a safe operation in which bleeding was controlled by intermittently occluding the IABOC and the patient was thus prevented from developing into severe hemorrhagic shock. We experienced a usefulness of IABOC for a patient with life-threatening intra-abdominal bleeding uncontrolled due to intra-abdominal adhesion during the perioperative period. However, organ dysfunctions caused by ischemia and reperfusion following intra aortic balloon occlusion must be prevented by shortening the occlusion time through use of an intermittent method such as described above. PMID- 11211751 TI - [A case of ventricular tachycardia immediately after electroconvulsive therapy in a schinzophrenic patient]. AB - A 33 year-old man weighting, 93 kg with schizophrenia underwent repeated electroconvulsive therapy (ECT) under general anesthesia with thiamylal 200 mg and suxamethonium 80 mg. On his fourth ECT, he developed ventricular tachycardia (VT) immediately after the treatment under general anesthesia with the same agents. The duration of VT was approximately 30 s. The VT returned to sinus rhythm without any special treatment. We speculate that light anesthesia with a small amount of thiopental associated with release of serum potassium caused by suxamethonium induced increased release of catecholamine by ECT to cause VT. After that incident, the patient underwent ECT six times under general anesthesia with thiamylal 250 mg and vecuronium 8 mg, in combination with preventive injection of magnesium sulfate 20 g without any cardiovascular complications. We conclude that the anesthetic management of patients undergoing ECT under general anesthesia should be paid a careful attention for cardiovascular instability, even if they do not have any heart diseases. PMID- 11211752 TI - [Anesthetic experience of emergency coronary artery bypass graft operation in a patient with cardioamyloidosis]. AB - A 76-year-old woman with acute myocardial infarction underwent an emergency coronary artery bypass graft operation. She developed cardiac failure and sick sinus syndrome before the surgery because she was with cardioamyloidosis. Therefore, intra-aortic balloon pumping and the pacemaker were used to maintain the hemodynamics prior to the operation. Anesthesia was induced with midazolam 5 mg, morphine 30 mg and pancuronium 5 mg, and maintained with 0.3-0.5% isoflurane in 50% nitrous oxide and 50% oxygen. Morphine 10 mg was also injected during the surgery, and the total dose of morphine 40 mg was administered. The pacemaker at 80 bpm was inserted and mexiletine 0.5 mg.kg-1.h-1 was given to prevent ventricular arrhythmias at weaning from cardio-pulmonary bypass. The surgical operation was successfully performed and the postoperative course was uneventful. A combination of light inhalation anesthesia with narcotics may be a choice for anesthetic management of patients with cardioamyloidosis as this method has less influence on hemodynamics. PMID- 11211753 TI - [Anesthetic management for thoracoscopic bullae resection using epidural anesthesia]. AB - We report the anesthetic management for elective thoracoscopic bullae resection (TBR) using high thoracic epidural (TE) anesthesia in awake patients. Pain and cough reflex caused by the surgical procedure could be controlled well with high TE anesthesia using 20-25 ml of 2% lidocaine. Respiratory and hemodynamic conditions remained stable during the surgical procedure. High TE anesthesia using a large dose of local anesthetic is thought to be suitable for TBR. PMID- 11211754 TI - [Hydrothorax during diagnostic laparoscopy]. AB - An 83-yr-old, 44-kg woman with a 2-month history of abdominal distension received diagnostic laparoscopy. Except for chronic treated hypertension, she was healthy. The preoperative chest X-ray demonstrated small pleural effusion occupying the lower left hemithorax, but she did not present with dyspnea or chest pain. After premedication with intravenous ranitidine 50 mg, anesthesia was induced with thiopental 150 mg, vecuronium 7 mg and maintained by 1-2% sevoflurane in 50% N2O/O2. SpO2 decreased after insufflation of CO2, but breath sound was audible on both lungs. At completion of operation, chest X-ray revealed the left hemilateral hydrothorax and 650 ml of pleural fluid was suctioned. Blood gas improved and the tracheal tube was removed. The diagnosis of tuberculous peritonitis was established by the demonstration of granulomas of the peritoneum. We speculated on four reasons for the increased pleural effusion on the left thorax: 1) Increase of systemic and capillary pressure caused by CO2 insufflation. 2) Increase of capillary permeability by tuberculous pleuritis. 3) Decrease of colloid osmotic pressure by hypoalbuminemia. 4) Decreased pleural fluid removal because of venous compression caused by increased intrathoracic pressure. Peritoneal insufflation of CO2 to create the pneumoperitoneum may induce hydrothorax in patients with tuberculous pleuritis. PMID- 11211755 TI - [Anesthesia for a patient with cardiac sarcoidosis]. AB - Anesthesia for a 49-year-old man with cardiac sarcoidosis is reported. Preoperative cardiac examination showed left ventricular dysfunction (ejection fraction = 27%) and myocardial conduction defects. In addition, his previous history included atrial fibrillation and cerebral infarction. Transesophageal echocardiography showed thrombus in the left appendage. Anesthesia was induced with fentanyl and diazepam and maintained with fentanyl and isoflurane. Perioperative hemodynamic monitoring included direct arterial pressure, central venous and pulmonary artery pressure and continuous cardiac output. In addition, transesophageal echocardiography was useful for watching thrombus in the left appendage. His hemodynamic condition was stable and no neurological complication was noted after anesthesia. PMID- 11211756 TI - [Marked bradycardia during anesthetic induction treated with temporary cardiac pacing in a patient with latent sick sinus syndrome]. AB - A 59 year-old woman with latent sick sinus syndrome was scheduled to undergo ophthalmic surgery including phacoemulsification and aspiration, vitrectomy, photocoagulation and intraocular lens under general anesthesia. Preoperative ECG showed sinus rhythms of 77 bpm without bradycardia or a sinus pause. Total intravenous anesthesia with propofol, fentanyl, ketamine and vecuronium was employed for the induction of anesthesia immediately followed by severe bradycardia with a rate of 36-40 bpm including sinus arrest and atrio/nodal escaped beats. Intravenous atropine was ineffective to restore the heart rate and then urgent temporary pacing was successfully applied to overcome bradycardia. The patient recovered uneventfully from anesthesia. She complained of being dizzy and faint with prominent bradycardia due to sick sinus syndrome three months after the surgery. Therefore she underwent permanent cardiac pacemaker implantation successfully. Temporary pacing is mandatory when anesthesia is given to surgical patients with latent sick sinus syndrome. PMID- 11211757 TI - [Comparison by simulation of the efficiency of surgical blood order equation (SBOE) with that of maximum surgical blood order schedule (MSBOS)]. AB - The maximum surgical blood order schedule (MSBOS) is used to promote efficient blood ordering practice for surgical patients. A surgical order equation (SBOE) was developed to calculate the number of units of red blood cells that should be ordered considering specific patient variables. We compared the efficiency of SBOE with that of the MSBOS by simulations. A retrospective study compared the SBOE with the MSBOS for ordering red blood cells units (MAP) in patients for six types of operations at our hospital. The SBOE was calculated as follows: SBOE (units) = mean blood loss (g)/200 - (preoperative Hb - postoperative Hb) divided by (40/body weight (kg)). The SBOE reduced the ordered units more effectively than the MSBOS. The SBOE reduces crossmatch-to-transfusion ratio (C/T ratio) from 1.2 to 1.6 but it would reduce the ordered units in statistical significance in only two of six types of operations. In conclusion, the SBOE could improve C/T ratio. PMID- 11211758 TI - [Effect of colforsin daropate hydrochloride after cardiopulmonary bypass]. AB - We evaluated the effects of colforsin daropate hydrochloride (CDH) after cardiopulmonary bypass (CPB) in comparison with milrinone. CDH or milrinone were given during and after CPB combined with cathecholamines so as to maintain mean arterial pressure (mABP > 60 mmHg) and cardiac index (CI > 3.0 l.min-1.m-2). Hemodynamics measurement was done immediately after CPB (A 1), one hour after CPB (A 2) and after the chest closure (A 3). In CDH group, mABP was significantly higher compared with milrinone group. Also, CDH group showed a significant reduction in the cases of combined use of dobutamine (at A 2, A 3) and norepinephrine (at A 1, A 2) compared with milrinone group. In conclusion, colforsin daropate hydrochloride exerts more inotropic effect and could reduce the necessity of combined use of cathecholamine compared with milrinone. PMID- 11211759 TI - [A comparison of the effectiveness of transtracheal heating and humidification system in maintaining body temperature during general anesthesia with low flow gases]. AB - We evaluated the effectiveness of transtracheal heating and humidification system in maintaining body temperature during general anesthesia with low flow gases in 12 gastric cancer patients. Patients were divided into two group; Control group A in which a hot-water circulating system was used and group B in which a transtracheal heating and humidification system by ANAMED HUMITUBE was used, during gastric cancer operation. Compared to the hot-water circulating system, the transtracheal heating and humidification system is more effective for maintaining body temperature and humidification after abdominal lavage by warm saline water. But there was no difference between the two groups about awakening from general anesthesia. We concluded that transtracheal heating and humidification system by ANAMED HUMITUBE is effective in maintaining body temperature under general anesthesia with low flow gases. PMID- 11211760 TI - [The Baxter AS 50 syringe pump: a comparison with propofol-specific syringe pumps]. AB - We used a Baxter AS 50 syringe pump for intravenous anesthesia with propofol, and compared it with a Grasby 3500 and a Terumo STC-525 X pumps, which are specifically designed for propofol infusion. The AS 50 pump is a programmable syringe infusion pump, which allows us to register up to 70 drug names in 10 categories and various infusion modes for drugs. There are 14 types of continuous infusion mode, a custom dilution mode, and three types of time infusion modes. The continuous infusion mode in mg.kg-1.h-1 is available for propofol anesthesia. Operation of this pump is simple and user-friendly, as with for the other propofol-specific pumps. Although the AS 50 pump is limited to a maximum bolus rate of 438 ml.h-1, this restriction is not a serious problem in clinical practice. The AS 50 pump is also equipped with an RS-232 C digital interface port to allow external remote monitoring or automated control. On-line simulation of blood propofol concentration is possible with a simulation program such as Propofol-Mon. Our impression is that the AS 50 pump is compact, easy to use, accurate and reliable for propofol anesthesia. PMID- 11211761 TI - [Evaluation of off-pump coronary artery bypass grafting based on systemic inflammatory response syndrome]. AB - Assessment of the less-invasiveness of off-pump coronary artery bypass grafting (OP-CAB) was made by the view point of systemic inflammatory response syndrome (SIRS). Single vessel OP-CAB with median sternotomy (MS(+)OP-CAB group, n = 13), single vessel OP-CAB without median sternotomy (MS(-)OP-CAB group, n = 9), two vessels conventional coronary artery bypass grafting (C-CAB) by normothermic extra corporeal circulation with steroid (methylprednisolone) (s(+)C-CAB group, n = 13), and two vessels C-CAB without steroid (s(-)C-CAB group, n = 13) were compared with each other. The criteria for SIRS was two or more of the following conditions: (1) temperature > 38.0 degrees C, (2) respiratory rate > 20 breaths/min, (3) heart rate > 90 beats/min, (4) white blood cells > 12,000 cells/mm3. Patients' date such as age, sex, risk factors, ejection fraction, operation time, aortic or LAD clamping time, frequency of SIRS, duration of SIRS, total application number of SIRS, mean application number of SIRS, hospitalization period, rate of renal or liver dysfunction were compared, and the following results were obtained. 1) MS(+)OP-CAB group had less-invasiveness than s(-)C-CAB group. The invasiveness of extra corporeal circulation was clear. 2) s(+)C-CAB group had equal invasiveness to MS(+)OP-CAB group. The anti-SIRS effect and organ protect effect of steroid was suggested. 3) MS(-)OP-CAB group had equal invasiveness to MS(+)OP-CAB group. The invasiveness of median full sternotomy was not so strong. PMID- 11211762 TI - [A case of Marie-Bamberger syndrome caused by growth hormone-producing lung cancer: problems associated with peri- and postoperative management of patients with growth hormone-producing tumors from the standpoint of the "second attack" theory]. AB - Marie-Bamberger syndrome is identical to pulmonary hypertrophic osteoarthropathy, and the causative factors have not been thoroughly clarified yet. Therefore, further studies of each case would seem to be useful to shed some light on the pathogenesis. We reported a 48-year-old man with primary lung cancer associated with clubbing of the fingers and hypertrophic osteoarthropathy. Chest CT portrayed a 10 x 6.5-cm bulky mass with central necrosis in the left upper lobe. The serum level of growth hormone (GH) showed about a twenty-fold increase over the normal upper limit. With the emergence of SIRS (Systemic Inflammatory Response Syndrome), the patient's general condition took a downhill course. We considered this state to be an oncological emergency and performed a semi-urgent operation. Immunohistochemical evaluation revealed a poorly differentiated adenocarcinoma with GH production. After treatment, the serum level of GH normalized and the clubbing and the periosteal changes of the bones resolved, which suggests that GH plays an etiologic role in Marie-Bamberger syndrome. Recent studies have indicated that GH has immunostimulatory effects. From the standpoint of the "second attack" theory, surgical stress seems to act on the immune system already activated by GH (so called "priming") in the form of a second attack, and trigger an excessive inflammatory response leading to postoperative organ injury in patients who suffer from GH-producing tumors. Thus, we should recognize this immanent risk and perform peri- and postoperative management for patients with GH-producing tumors. PMID- 11211763 TI - [Efficacy of additional Dor approach to coronary bypass grafting in severe left ventricular dysfunction with large akinetic area]. AB - Between January 1994 and August 1999, we experienced 16 cases of coronary artery bypass grafting (CABG) in severe left ventricular dysfunction with left ventricular ejection fraction (LVEF) < or = 40%. Four had additional endoventricular patch plasty in large postinfarction akinetic scars, the so called Dor approach, to CABG (group D). Eleven had only CABG, or CABG and mitral annuloplasty (group C). One had linear repair after the resection of the left ventricular aneurysm. One died of sustained low output syndrome 5 months after the operation in group C. Fractioning shortening and left ventricular diastolic diameter were not changed after the operation in group C. On the other hand, in group D, there were no complications after the operation, LVEF was significantly improved from 31.5 +/- 4.9% to 62.5 +/- 5.9% (p < 0.01) and the left ventricular end-diastolic volume index was reduced from 118 +/- 23 ml/m2 to 74 +/- 12 ml/m2 (p < 0.01). The Dor approach is considered to be a safe and effective additional procedure to CABG in severe patients with a large akinetic antero-septal segment. PMID- 11211765 TI - [Two cases of patch closure of pericardial defects using fascia lata after pulmonary resection with pericardiectomy]. AB - We reported two cases of patch closure of pericardial defects using fascia lata after pulmonary resection with pericardiectomy. We confirm many advantages of this method-cheap, low risk of infection, tight tissue and easy technique in a short time with no skilled hand. PMID- 11211764 TI - [Efficacy of modified ultrafiltration in reoperation for valvular disease]. AB - We evaluated the efficacy of modified ultrafiltration (MUF) in reoperation for valvular disease. Fourteen patients were divide into two groups consisting of a control group (n = 6) and a MUF group (n = 8). MUF was carried out for fifteen minutes immediately after the completion of cardiopulmonary bypass. The blood flow through the ultrafilter was 300 ml/min and about 1,200 ml of water was removed. The hematocrit elevated significantly from 25% to 31% in the MUF group (p < 0.05). The percentage of the increase in body weight after the operation in the MUF group was significantly less than that in the control group (3.3 +/- 3.1% vs 8.3 +/- 4.3%, p < 0.05). The PaO2/FIO2 after the operation in the MUF group was significantly higher than that in the control group (376 +/- 125 mmHg vs 242 +/- 79 mmHg, p < 0.05). The duration of mechanical ventilation in the MUF group was significantly less than that in the control group (1.1 +/- 1.1 days vs 5.3 +/ 3.3 days, p < 0.05). In conclusion, MUF is useful to hemoconcentrate, reduce postoperative body weight gain and promote early recovery of pulmonary function in reoperation for valvular disease. PMID- 11211766 TI - [Experiences of minimally invasive great saphenous vein graft harvest using with endopath]. AB - We have experienced 20 cases of minimally invasive great saphenous vein graft harvest using with endoscopy, Endopath, from March 1999. As we experienced cases, we can harvest great saphenous vein graft, about 30-40 cm in size, from only two 4-cm incisions for about 50 minutes. There are no wound infection, pain, and edema. Great saphenous vein graft harvesting with Endopath is less invasive, painless after surgery and makes patients satisfied about cosmetic problem. PMID- 11211767 TI - [Tricuspid valve replacement using right heart bypass in patient with liver cirrhosis]. AB - A successful case with liver cirrhosis underwent re-tricuspid valve replacement (TVR) using right heart bypass is reported herein. A 59-year-old lady previously undergone tricuspid valve replacement with bioprosthetic valve had suffered from exertional fatigue as the feature of congestive heart failure. She also presented severe liver dysfunction owing to chronic hepatitis and cardiac liver cirrhosis. She was diagnosed with structural deterioration of bioprosthesis in tricuspid position. She underwent re-TVR with right heart bypass consisted of centrifugal pump, heparin coating circuit and blood reservoir. This system lacked of membranous oxygenator in order not to activate various kinds of chemical mediator which leads to postoperative liver dysfunction. Postoperative course was uneventful and she is doing well 1 year after the operation. Although the mortality of the TVR in the patient with cirrhosis remains still high, this new technique seems to provide better outcome in this kind of patients. PMID- 11211768 TI - [Inferior mini-sternotomy for off-pump CABG using bilateral internal thoracic arteries]. AB - Case 1: A 72-year-old woman with effort angina underwent coronary artery bypass grafting. A preoperative coronary angiogram showed 90% stenosis in the proximal main RCA, and total occlusion in the proximal LAD, distal of which was an area well supplied by collaterals from the RCA. This patient had previously undergone right upper lobectomy due to lung cancer. With a skin incision of 8 cm, the LITA was inserted into the LAD and the RITA was inserted into the mid RCA through an inferior mini-sternotomy while the heart was beating. Case 2: A 69-year-old man with effort angina underwent CABG. A preoperative coronary angiogram showed 90% stenosis in the proximal main RCA, 75% stenosis in the PDA and total occlusion in the proximal LAD, distal of which was an area well supplied by collaterals from the RCA. With a skin incision of 11 cm, the LITA was inserted into the LAD, the RITA into the mid-RCA and the radial artery graft attached to the RITA was grafted to the PDA through an inferior mini-sternotomy while the heart was beating. In both cases, the sternum was not cut transversely in order to prevent injury to the ITAs and pseudo-joint formation. With the use of this technique, exposure of the LAD and RCA was excellent. Postoperative recovery in both patients was uneventful and postoperative angiograms revealed widely patent grafts. This technique was very useful when performing off-pump CABG using bilateral ITAs. PMID- 11211769 TI - [The estimation of the effectiveness of GRF glue in the respiratory]. AB - We had reported on the basis of experimental findings that the efficacy of protecting the suture line in tracheoplasty by using a self-fascia lata and GRF glue. This time we investigated the effectiveness of GRF glue in the respiratory surgery on the basis of clinical findings. All ten cases in which GRF glue was used resulted in an excellent outcome, namely, GRF glue prevented from air leakage, bleeding and leakage of chyle. Moreover, it was not recognized that any grave side effects occurred in any cases after using GRF glue. We could conclude that GRF glue was a useful material for the respiratory surgery, especially for the case that had a dead space after lobectomy. However its price is not inexpensive, therefore, there seems need to restrict the use of GRF glue--for example--to cases of Giant bulla resection, residual of a large dead space as a postoperative possibility and chemotherapy performed before an operation, and so on. PMID- 11211770 TI - [A case of surgically treated left atrial myxoma following acute multiple embolism including cerebral embolism]. AB - The patient was a 59-year-old female who was admitted to the hospital due to acute pain of bilateral legs, a numbness of right hand and anarthria. Angiography of extremities revealed total occlusion of right ulnar artery, left radial artery and bilateral popliteal arteries. Brain MRI revealed multiple small infarctions. Echocardiography revealed a mass in the left atrium. She was diagnosed as multiple embolism including cerebral embolism caused by left atrial myxoma. Open heart surgery immediately after the attack is generally considered contraindicated due to problems of hemorrhagic infarction or brain edema. But, relapse of embolism may deteriorate the condition and miss the timing of surgery. Thus we performed removal of left atrial myxoma 4 days after the attack. The postoperative course was uneventful. This is a few report about open heart surgery immediately after the attack. We report about the indication and the optimal timing of open heart surgery following cerebral embolism. PMID- 11211771 TI - [A case of tracheo-bronchial stenosis after extended end-to-end aortic arch anastomosis for interrupted aortic arch treated with suspension of the ascending artery and pulmonary artery]. AB - A 9-day-old boy had pulmonary artery banding and extended end-to-end aortic arch anastomosis for ventricular septal defect (VSD) and type A interrupted aortic arch. Severe dyspnea gradually developed. At 3 months of age, intracardiac repair of VSD was performed. Weaning from the ventilator was difficult. Endoscopic examination and chest CT revealed stenosis of the right and left main bronchi and compression of tracheal bifurcation and the right and left main bronchi by the ascending aorta and pulmonary artery. Suspension of the ascending aorta and pulmonary artery was performed 15 days after VSD closure. Nine days after this procedure, the patient was weaned from respirator. Postoperative course was uneventful. Bronchial stenosis may be caused from extended end-to-end aortic arch anastomosis. PMID- 11211772 TI - [A case report on two stage operation of dissecting aneurysm of DeBakey IIIb type associated with dense pulmonary adhesion]. AB - Successful surgical treatment of chronic dissecting aneurysm (DeBakey IIIb type) in a 50-year-old man was reported. His left lung was tightly adhered to the aneurysm and the chest wall, because he had a previous operation history for pyothorax. This patient showed copious pulmonary bleeding by the pulmonary injury during adhesiotomy. We selected the two stage operation for deducting operation risks, and finished the first operation at the end of adhesiotomy. Some pieces of e-PTFE sheet had been put between lung and thoracic wall, or aneurysm. After a week, waiting the cure of this pulmonary injury, the second operation was performed with a small quantity of pulmonary bleeding. There wasn't fresh pulmonary adhesion because of protection by e-PTFE sheet. The two stage operation was useful in cases associated with dense pulmonary adhesion. PMID- 11211773 TI - [Desmoid tumor of the chest wall infiltrating into the brachial plexus: report of a resected case]. AB - We report a case of a desmoid tumor which developed in the apex of the chest wall. A 18-year-old woman was admitted with left shoulder pain. Chest X-ray showed a mass shadow in the left upper lung field. Chest MRI demonstrated the mass infiltrated into the left brachial plexus. A desmoid tumor was suspected on percutaneous needle biopsy. Resection of the tumor was performed. The mass was 13 x 9 x 5 cm in size and diagnosed pathologically as desmoid tumor. Adjunctive postoperative radiation therapy of 60 Gy was done. Postoperative course was uneventful except motor disturbances of the left fingers. At 15 months postoperatively, there was no evidence of recurrence. PMID- 11211774 TI - [A case treated with thoracoscopic wedge resection for cT1N0M0 lung cancer complicated with both chronic obstructive pulmonary disease (COPD) and hypofunction of left ventricle in a octogenarian]. AB - A 81-year-old man who had medical treatment for both COPD and essential hypertension was admitted to our institution for evaluation of shadows of a mass in the right upper field on chest X-rays. The tumor was 3.0 cm in diameter on chest CT and diagnosed to be bronchogenic squamous cell carcinoma on the basis of findings of bronchoscopic brushing. The thoracoscopic wedge resection was undergone for cT1N0M0 lung cancer in the high-risk patient. Postoperative course was uneventful and the patient was discharged one month after the operation. He is now doing well without relapse of cancer a year and half after the operation. PMID- 11211775 TI - [Leiomyoma of the esophagus shown as a cervical tumor]. AB - A 44-year-old female was admitted to our hospital because of the left cervical tumor. Radiologic examination showed that the tumor was 5 cm in diameter and was inhomogeneous. The tumor was spread to the upper mediastinum. Esophagoscopy showed that the tumor was covered by the normal mucosa. Percutaneous fine needle biopsy did not appear the histopathological diagnosis. The patient underwent surgical resection through the cervical approach and the tumor was located between the mucosal and muscular layers of the esophagus. The tumor was enucleated without any complication. Histopathological diagnosis was leiomyoma. Postoperative course was uneventful. Expecting diagnosis and positive complete resection is recommended for leiomyoma of the esophagus. PMID- 11211776 TI - [Clinical study of operated nine thymic carcinomas]. AB - Nine cases of thymic carcinoma (5 males and 4 females) were operated in our hospital between 1990 and 1998. These cases included 4 squamous cell carcinomas, 2 small cell carcinomas, 2 undifferentiated carcinomas and one adenocarcinoma. Preoperative chemotherapy were performed in 3 cases. All cases underwent median sternotomy followed by mediastinal irradiation, 4 had total resection of the tumor, 2 had subtotal resection and 3 had exploratory thoracotomy followed by mediastinal irradiation. Adjuvant chemotherapy were administered in 4 cases and re-operation were performed in 2 cases. We applied Masaoka's clinical staging for thymoma, nine cases consisted of 6 stage III cases, 2 stage IV b cases and one stage IV a case. Within 2 years after operation, 3 cases (two complete resection cases and one exploratory thoracotomy case) were died of the carcinoma. However, two cases of squamous cell carcinoma have been alive more than 5 years after surgery followed by chemoradiation. The remaining 4 patients are alive either with or without the carcinoma after 7 to 28 months after operation. Thymic carcinoma is not so common mediastinal tumor but is expected to increase in the future. The treatment of thymic carcinoma remains a controversial matter and the survival is poor compared with invasive thymoma, but multimodal-therapy would contribute to improvement of the results in treatment for thymic carcinoma especially in squamous cell carcinoma. PMID- 11211777 TI - [A case report of Ebstein's anomaly treated with Hetzer's procedure]. AB - A 27-year-old male who had been diagnosed with Ebstein's anomaly was admitted with uncontrollable congestive heart failure. The echocardiogram revealed severe tricuspid valve incompetence and the electrocardiogram showed atrial fibrillation. He underwent Hetzer's repair procedure for tricuspid valve incompetence and Minzioni's right atrial isolation technique to restore sinus rhythm. His congestive heart failure quickly disappeared and sinus rhythm was restored after operation. He was discharged 3 weeks postoperatively and remains well 22 months after his operation. Hetzer's technique for tricuspid valve repair in Ebstein's anomaly restructures the valve mechanism at the level of the true tricuspid anulus by using the most mobile leaflet for valve closure without plication of the atrialized chamber. We conclude that Hetzer's procedure is an effective operation for Ebstein's anomaly. PMID- 11211779 TI - [A study on chest radiographs in medical check-ups for over-staying foreigners]. AB - During the past nine years from 1991 to 1999, Minatomachi Medical Center and other organizations have provided free medical check-ups for foreigners in Kanagawa, Tokyo and Chiba. Eighty-five percent of the total of the 2370 examined were over-staying foreigners who were not covered by national health insurance system. The ratio of male to female was two to one and the most of them were in the twenties and thirties. As for their ethnic origins from forty-three countries, the Filipinos were the largest numbers, followed by Koreans, Iranians, Bangladeshi, and Chinese/Taiwanese. As a result of chest radiographs, 82% were normal, 8.3% mostly normal, 9.6% tuberculosis shadow (TBS) including active, non active and previous, 0.09% suspected pneumonia, 0.05% suspected cardiac disease, and 0.05% suspected sarcoidosis. The TBS and active tuberculosis (ATB) rates of all examined were 9.6% and 0.69% respectively. There was no significant difference in each TBS and ATB rate between the two sexes. Seen from the age group, it was found that the more aged they were, the higher the TBS and the ATB rates were. The TBS and the ATB rates were 24.6% and 2.73% in the Koreans, 10.7% and 0% in the Chinese/Taiwanese, 10.2% and 0.65% in the Filipinos, 11.3% and 1.44% in the South-East Asians, 6.3% and 0.25% in the South Asians, 2.3% and 0% in the Iranians, 3.7% and 0% in the sub-Saharan Africans, 8.5% and 0.61% in the Latin Americans, and 0% and 0% in the Europeans/North Americans. Based on a presumed ATB rate of 0.75%, approximately two thousand cases with ATB could be calculated to exist among the estimated 270,000 over-staying foreigners. It is, therefore, important to give them more frequent medical check-ups for early detection of latent cases with ATB. PMID- 11211778 TI - [The causes of death in patients with non-MDR pulmonary tuberculosis in our hospital]. AB - We studied the causes of death in 295 patients (mean (+/- SD) age 70.5 +/- 13.2 y.o.) with active non-MDR pulmonary tuberculosis who died in our hospital between 1991 and 1999. A hundred and twenty eight patients (43.4%, group A) died of tuberculosis, while 167 patients (56.6%) of other accompanying diseases. In 46 patients of the latter (15.6%, group B), pulmonary tuberculosis gave an unfavorable impact on their clinical course. In these patients the extent of pulmonary tuberculosis on chest roentgenograph was similar with the remaining 121 patients who also died of the accompanying diseases (41.0%, group C) and was less severe than those of the group A patients. Their nutritional conditions measured by serum albumin and choline-esterase level on admission, however, were as low as those of the group A patients and distinctly worse than those of the group C patients. Most patients of groups A and B died within 3 months after admission, while less than half patients of group C died during the same period. The age frequency distribution of the patients in groups B and C had a single peak in the age group 70 to 89, while that in group A showed two peaks, one similar peak as in groups B and C, and another peak in the age group 50 to 59. The numbers of homeless patients, of the patients with extensive cavitary lesions, and of the patients who died of ARDS (Adult Respiratory Distress Syndrome) or severe pneumothorax in group A were the most also in the age group 50 to 59, indicating that the patients' delay in admitting to hospitals was the major cause of high motality in this age group. As to detailed causes of death in group A, patients died of respiratory failure (32 cases), emaciation (28 cases), progression of pulmonary tuberculosis (20 cases), ARDS (15 cases), tuberculosis-related diseases such as pneumothorax, hemoptysis, and DIC (24 cases). In groups B and C patients died of organ failure (36 cases), infectious diseases (33 cases) and malignancy (30 cases). The total number of died patients has increased, and the proportion of cases dying of ARDS and infectious diseases has increased statistically significantly recently. PMID- 11211780 TI - [In vitro antimycobacterial activities of a new quinolone, balofloxacin]. AB - Balofloxacin (BLFX), a newly developed fluoroquinolone, was studied for its in vitro antimycobacterial activity by the agar dilution method with 7H11 agar medium. The MIC90s were as follows: 0.39 microgram/ml for M. tuberculosis, > 50 micrograms/ml for M. avium, > 50 micrograms/ml for M. intracellulare, 0.39 microgram/ml for M. kansasii, 0.39 microgram/ml for M. fortuitum, > 50 micrograms/ml for M. abscessus, and 50 micrograms/ml for M. chelonae. The antimycobacterial activity of BLFX was comparable or slightly inferior to that of levofloxacin (LVFX). Considering the present findings and pharmacokinetics of BFLX, it appears that BFLX may achieve favorable outcome in the treatment of patients with infection due to M. tuberculosis, M. kansasii, or M. fortuitum similar to that of ofloxacin or LVFX. PMID- 11211781 TI - [Effectiveness and problems of PZA-containing 6-month regimen for the treatment of new pulmonary tuberculosis patients]. AB - One third of the world population has been infected with Mycobacterium tuberculosis, and the number of tuberculosis will increase worldwide without more effective programs of tuberculosis control. Despite of the presence of very potent anti-tuberculosis drugs the global tuberculosis situation is still very serious, and such gloomy feature are caused, at least partly, by the failures in the treatment of tuberculosis. The most important factor for the failure in chemotherapy is incompliance of the patients to the regimens. History of the chemotherapy of tuberculosis can be said as the history of the efforts to reduce such defaulters. Modern chemotherapy of tuberculosis has started from the discovery of streptomycin. Streptomycin monotherapy could improve temporally symptoms and bacteriological status, but could not cure the patients with moderately advanced pulmonary tuberculosis because of the emerge of drug resistant tuberculosis. This problem was overcome by combining use of para aminosalicylate and/or isoniazid developed later on. About 97% of patients with pulmonary tuberculosis became bacteriologically quiescent by the 12 months of streptomycin, para-aminosalicylate and isoniazid. Since 1950s through 1970s three drug combination of streptomycin, para-aminosalicylate and isoniazid had been the standard regimen for the treatment of tuberculosis. By the introduction of rifampicin, the duration of chemotherapy could be shortened to 9 months. Subsequent to the successful animal experiments carried out by Grosset which demonstrated that the addition of pyrazinamide for initial 2 months to the standard two-drug combination (isoniazid and rifampicin) could remarkably shorten the duration of chemotherapy, many clinical trials have been done all over the world to compare the efficacy and safety of pyrazinamide-containing intensified short-course regimen with those of standard regimen without pyrazinamide. Sputum negative conversion rates after 2 months of treatment with PZA-regimen was 70 95%, and the relapse rates after the completion of the treatment course were less than 4%. The incidence of adverse events was less than 4%. The pyrazinamide containing 6 months short-course regimens has been established as a new standard regimen for the initial treatment of pulmonary tuberculosis worldwide. But, in Japan, this regimen had not been adapted as the standard until April 1996 because of undue fear for high incidence of liver toxicity induced by pyrazinamide. However, in many clinical trials carried out in various parts of the world did not show any causative relationship between the higher incidence of liver toxicity and pyrazinamide. According to our own experience in Fukujuji Hospital, Japan Anti-tuberculosis Association, the frequency of drug induced hepatitis among 632 patients with normal liver function at the onset of chemotherapy was 7.9 percent (50/632) when treated with pyrazinamide-containing regimens, and was similar to that among 412 patients treated with other regimens without pyrazinamide (7.3 percent 30/412). These figures were higher than those reported in the literatures. The risk factors of drug-induced hepatitis so far reported included elderly, positive hepatitis C virus antibody, low serum albumin and so on. Such known risk factors could not wholly explain the higher rate of liver dysfunction observed among our Japanese patients. We have examined additional factors affecting the frequency of drug-induced hepatitis in our hospital, and noticed that the past history of gastrectomy and over-dosing of isoniazid (> or = 7.5 mg/kg) and/or pyrazinamide (> or = 30 mg) were relating to the higher incidence of drug-induced hepatitis. Another important finding is that the relapse rate among patients complicated with diabetes mellitus is significantly higher than that of the patients without diabetes mellitus (6.31/100 person-years vs 0.90/100 person-years, P < 0.001). Further research will need whether the patients complicated with diabetes mellitus have any immunological deficient to kill Mycobacterium tuberculosis. WHO, CDC and ATS recommended that 4-drug regimen including pyrazinamide for the initial treatment of all cases of tuberculosis. Considering that the incidence of initial resistance to isoniazid is 4.4% in Japan, we should start to treat all cases of newly diagnosed tuberculosis with pyrazinamide-containing regimen (isoniazid, rifampicin, pyrazinamide, plus streptomycin or ethambutol). To do this, further studies on the risk factors of drug-induced hepatitis are urgently needed. PMID- 11211782 TI - [Usefulness of self ligation mediated polymerase chain reaction: a rapid method for fingerprinting in molecular epidemiology of tuberculosis]. AB - Restriction fragment length polymorphism (RFLP) analysis based on the insertion sequence IS 6110 has been used as one of the powerful tools for epidemiological study of tuberculosis. However this technique requires more than 1 micro-gram of DNA and two days for completion. To overcome these inconvenience, we have modified a PCR-based method, self ligation mediated PCR (SL-PCR) on the molecular epidemiological study. This method uses a pair of primers whose orientations are from inside to outside of IS 6110. The DNA fragments flanking IS 6110 are amplified by the PCR by using the Sau 3A I digested and ligated chromosomal DNA of Mycobacterium tuberculosis strains. By using this method, M. tuberculosis strains can be differentiated within 8 hours. PMID- 11211783 TI - [Recent advances in the research on TGF-beta/Smad signaling pathways]. PMID- 11211784 TI - [Molecular mechanism of inactivation of TGF-beta receptors during carcinogenesis]. PMID- 11211785 TI - [Gastrointestinal tumorigenesis in Smad4 mutant mice]. PMID- 11211786 TI - [Aberrations of Smad genes in human digestive tract cancers]. PMID- 11211787 TI - [Regulation of morphogenesis and regeneration of the kidney by the activin signaling system]. PMID- 11211788 TI - [Applications of puromycin for evolutionary molecular engineering of proteins and analysis of gene networks]. PMID- 11211789 TI - [Protein folding and its structural topology]. PMID- 11211790 TI - [The frontier of the artificial heart]. PMID- 11211791 TI - Inhibitory effect of Rumex Japonicus Houtt on the porphyrin photooxidative reaction. AB - Rumex Japonicus Houtt (RJH), a plant indigenous to Okinawa, Japan, has been used traditionally by the local people for treatment of acute and chronic cutaneous diseases; however, its pharmacological effect is not clearly understood. To investigate its active function, we examined the antioxidative effect of RJH on the hematoporphyrin-induced photooxidative reaction. We measured intracellular reactive oxygen species (ROS) in cultured transformed human vascular endothelial cells (ECV-304) by flow cytometry, lipid peroxide (LPO) in erythrocyte ghosts by spectrofluorometry, and hemolysis by spectrophotometry. Results showed the generation of intracellular ROS in ECV-304, LPO production in erythrocyte ghosts, and hemolysis after visible light irradiation in the presence of hematoporphyrin. In the RJH root extract treated group, generation of intracellular ROS, LPO production, and hemolysis were inhibited significantly. It has been reported that the RJH root contains emodin and chrysophanic acid. In our study, three fractions were separated from the RJH root extract by thin layer chromatography (TLC). We found that fraction 1 (near the origin) showed a strong inhibitory effect on LPO levels; however, fraction 2 (equal to emodin) and fraction 3 (equal to chrysophanic acid) showed no inhibitory effect on LPO levels. Our experiments verified that RJH has an antioxidative effect against photohemolysis and supports our hypothesis that RJH may have potential as a protective agent against oxidative stress associated with some diseases such as porphyrias. PMID- 11211792 TI - Pedunculated melanoma with pulmonary and bony metastases. AB - We report a patient with pedunculated melanoma. Rounded and epithelioid-type melanoma cells had proliferated in the epidermis and massively into the deep dermis in the pedunculated nodule. At the base of the pedicle, lengtiginous-type melanoma cells formed nests of various sizes in the epidermis extending ten or more rete ridges beyond the site of invasion. Thus, this case shows that a pedunculated melanoma is not necessarily a variant of nodular melanoma. Six years after the primary operation, late recurrence was detected in regional lymph nodes, and nine years after the initial operation, the patient was found to have three large metastatic nodules, up to 8.5 cm in longest diameter, in her lung and bone. Although she died six months after the metastasectomy, prompt surgical excision of the primary tumor and metastasectomy can provide longer survival. PMID- 11211793 TI - Amblyomma testudinarium tick bite: one case of engorged adult and a case of extraordinary number of larval tick infestation. AB - This paper reports two recent cases of tick bite due to Amblyomma testudinarium. The first case was an 86-year-old farmer infested with a fully engorged adult tick attached on his inguinal region. The second case was a 57-year-old male infested with an extraordinarily large number of larval ticks (> 100 larvae). The ticks were identified as A. testudinarium based on morphological characteristics. To our knowledge, the latter case is the eleventh case of larval tick bites among all tick species and the fourth case with larval A. testudinarium in Japan. PMID- 11211794 TI - Three cases of polyarteritis nodosa cutanea and a review of the literature. AB - We describe three cases of polyarteritis nodosa cutanea (PNC) showing necrotizing arteritis and only cutaneous lesions without systemic symptoms or visceral involvement for eleven, six, and three years after the onset of the disease. Since it was first described, there has been continuous controversy as to whether PNC progresses to systemic PN. Some cases have been described which had begun with a cutaneous lesion and progressed to the systemic form 19 and 18 years after the onset of the disease, so we believe that long term follow-up of this disease is essential. PMID- 11211796 TI - A case of acinic cell adenocarcinoma on the left hemifacial area. AB - Acinic cell adenocarcinoma is a rare salivary gland tumor which predominantly occurs in the parotid gland. A 46-year-old man presented with a left preauricular mass of one month duration; the pathologic report showed acinic cell adenocarcinoma. He was transferred to the oral and maxillofacial surgery department, and a total parotidectomy was performed. We present this interesting case of acinic cell adenocarcinoma from the parotid gland with cutaneous involvement. PMID- 11211795 TI - Colchicine treatment in a patient with neutrophilic dermatosis associated with rheumatoid arthritis. AB - Neutrophilic dermatoses (ND) are characterized by epidermal and dermal infiltrates of polymorphonuclear leukocytes (PMN), without any infectious or other detectable agents as a cause. We describe a case of ND, which very rapidly improved upon colchicine treatment. The patient was a 67-year-old female with an 8-month history of dusky-red, tender, swollen plaques and nodules with superimposed vesicles and bullae on the buttocks, hands, and ankles associated with rheumatoid arthritis. The diagnosis of ND was made on the basis of the clinical and histopathological features of the skin lesions. She was treated with 0.6 mg of oral colchicine twice daily. Within one week, the erythematous plaques and arthralgia began to recede and disappeared within four weeks. In our case, colchicine seemed to improve the signs and symptoms of ND and appeared to be more effective than the other drugs we had used. PMID- 11211797 TI - Sweet's syndrome with abscess-like lesions in a patient with acute myelogenous leukemia. AB - We describe a 49-year-old man with acute myelogenous leukemia associated with Sweet's syndrome and abscess-like lesions mimicking an infectious disease. Although blisters may be included in the clinical spectrum, frank non-infectious abscesses have not been reported as far as we know. Clinicians should be familiar with this clinical and histopathologic variant of Sweet's syndrome. It is mandatory to make every effort to find an infectious cause for abscesses before a diagnosis of Sweet's syndrome is made. PMID- 11211798 TI - Non-ulcerative basal cell carcinoma arising on the genitalia. AB - We report two cases of basal cell carcinoma (BCC) arising on the genitalia. The first case was a 49-year-old male who became aware of a dull erythematous plaque with a keratotic surface on his scrotal skin, and the second case was a 44-year old female suffering from a keratotic plaque on her right vulvar region. Neither lesion was ulcerative. Both were resected under local anesthesia following a clinical diagnosis of angiokeratoma for the former and seborrheic keratosis or BCC for the latter lesion. Histopathological study revealed that both lesions were BCC. Many questions regarding the pathogenesis of BCC still remain to be clarified. Because most of the reported cases have been ulcerative lesions and the genital region is an uncommon site for BCCs, caution should be taken in cases in whom a clinically non-ulcerative tumor suspected to be angiokeratoma or seborrheic keratosis arises in this region. PMID- 11211799 TI - Unusual annular pustular psoriasis in a patient with type C hepatitis. PMID- 11211800 TI - E-cadherin expression is frequently reduced in infiltrative basal cell carcinoma. PMID- 11211801 TI - Evolution of Dowling Degos disease. PMID- 11211802 TI - [Clinical usefulness of cross-linked N-telopeptide of type I collagen (NTx) as a bone metastatic marker in patients with prostate cancer--comparison with serum PICP, PINP and ICTP]. AB - Type I collagen cross-linked N-telopeptide (NTx) in urine, the degraded form of type I collagen cross-linked in bone, has been evaluated as a marker of bone resorption. In this study, the clinical usefulness of NTx as a marker of bone metastasis of prostate cancer was compared with that the carboxyterminal propeptide of type I procollagen (PICP), the aminoterminal propeptide of type I procollagen (PINP), and the pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) in serum. We assessed 37 cases of prostatic cancer in which the diagnosis had been confirmed pathologically. The patients were 15 patients with prostatic cancer with bone metastasis (before treatment or during a relapse) (Group 1); 11 patients, with bone metastasis, but for whom treatment was effective and condition had stabilized (Group 2); and 11 patients, with localized prostatic cancer and no evidence of bone metastasis (Group 3). The serum PICP, PINP, and ICTP levels and concentration of NTx in urine were compared among the three groups with the Mann-Whitney U test, with p values less than 0.05 considered significant. Urine NTx concentrations in Groups 1, 2 and 3 were 539.3 +/- 202.9, 160.6 +/- 97.6 and 48.6 +/- 7.6 nMBCE/mMCr, respectively. The differences between the Group 1 and Group 2 and between Group 1 and Group 3 were significant (p < 0.01 and p < 0.001). The differences between Group 1 and Group 3 and between Group 2 and Group 3 were significant for serum PICP, PINP and ICTP concentrations (p < 0.05). The correlation coefficient between urine NTx and each serum bone metabolic marker was 0.8 for PICP, 0.4 for PINP and 0.5 for ICTP. These bone metabolic markers are promising clinical markers of bone metastatic and may be useful for prediction of therapeutic efficacy and recurrence in bone and quantification of the extent of bone metastates. PMID- 11211803 TI - [Clinical study of prostate cancer: statistical analysis of 107 cases in the past 12 years]. AB - One hundred and seven patients with prostate cancer were treated at Mie University Hospital during the past 12 years between 1988 and 1999. They were between 53 and 83 years old, with an average age of 70.8 years old. The clinical stage was defined as A, B, C and D in 3 (2.8%), 19 (17.8%), 50 (46.7%) and 35 (32.7%) patients, respectively. At initial diagnosis, the tumor was well, moderately and poorly differentiated adenocarcinoma in 26 (24.3%), 47 (43.9%) and 34 (31.8%) patients, respectively. The median follow-up period was 52.3 months. The overall 1, 3 and 5-year survival rates were 98.0%, 86.8% and 75.2%, respectively. The 5-year survival rates for stage A, B, C and D were 100%, 93.8%, 82.1% and 56.9%, respectively. A significant difference (p = 0.017) in 5-year survival rate was noted between stage C and D. The 5-year survival rate was 100% for well differentiated, 78.0% for moderately differentiated, and 53.2% for poorly differentiated adenocarcinoma. A significant difference (p = 0.0016) in the 5-year survival rate was noted between well differentiated and poorly differentiated adenocarcinoma. According to the therapy, the 5-year survival rate in stage C was 86.2% for the radical prostatectomy group and 84.0% for the endocrine therapy group. There was no significant difference between these 2 treatment groups. Endocrine therapies, classified into maximum androgen blockade (MAB) and endocrine therapy other than MAB were performed for stage D as an initial therapy. Although the prognosis in the patients treated with MAB was better than that with other endocrine therapies, there was no significant difference between these 2 endocrine treatment groups. PMID- 11211804 TI - [Results of treatment for germ cell tumor--dose intensity of chemotherapy and residual masses after chemotherapy]. AB - We reviewed the treatment results in 44 patients with germ cell tumor and the significance of % dose intensity of Cisplatin and tumor marker half-life of induction chemotherapy and discussed the necessity of surgical resection of the postchemotherapy residual tumor. The 5-year survival rate calculated by the Kaplan-Meier method was 83.6% in total, and 95.2, 75.8 and 47.6% for good, intermediate and poor prognosis, respectively. Of the 29 metastatic cases treated by chemotherapy, 5 (17.2%) achieved complete response (CR) and 15 (51.7%) partial response, and % dose intensity of Cisplatin were 75.4% in total and 86.4 +/- 8.6, 71.6 +/- 11.1, 84.3 +/- 8.3 and 62.2 +/- 11.0% in CR, PR, NC and PD. Dose intensity was correlated with the clinical response and the prognosis. Of the 12 PR cases without teratoma elements, two had salvage surgery, five had additional chemotherapy and five were followed by surveillance. One case followed by surveillance died of the disease, another one with additional chemotherapy was alive with the disease and the others were alive with no evidence of disease. Surgical resection is an effective treatment to remove residual masses, but observation may also be considered in the cases without teratoma elements. PMID- 11211805 TI - [A compound tumor in the adrenal medulla--pheochromocytoma combined with ganglioneuroma: a case report]. AB - We report a case of a compound adrenal medullary tumor. A 63-year-old woman was referred to our hospital for examination of a right adrenal tumor, incidentally found by abdominal computed tomography (CT). CT and magnetic resonance imaging (MRI) revealed a round heterogeneous tumor, 5 cm in diameter, on the upper pole of the right kidney. A view of the total body scan demonstrated the uptake into the tumor after the injection of 123I-metaiodobenzyl-guanidine. Serum and urinary adrenaline levels were slightly elevated, and urinary excretion of vanillylmandelic acid was markedly elevated. Her blood pressure was normal. From these findings, the tumor was suspected to be a pheochromocytoma of the right adrenal gland and was resected reteroperitoneally. Pathological diagnosis was a compound adrenal medullary tumor, which was composed of pheochromocytoma and ganglioneuroma. This combination of the adrenal medullary tumor is extremely rare, and to date this case may be the sixth case in the Japanese medical literature. PMID- 11211806 TI - [A case of retroperitoneal teratoma difficult to distinguish from adrenal myelolipoma]. AB - A 59-year-old man presented to our hospital suspected of having cholelithiasis. Computed tomography (CT) scan revealed a left retroperitoneal solid tumor cephalad to the kidney, 7 x 8 x 9 cm in size with mostly a fatty density area and focal calcification. Magnetic resonance imaging (MRI) on T1 and T2 weighted images showed a high intensity mass. Angiography revealed the hypovascular tumor. Although we had suspected it to be an adrenal myelolipoma, tumorectomy was performed because of its size. Pathological diagnosis was mature teratoma. Although retroperitoneal teratoma contains fas, cyst, soft tissue and calcification, the proportion of fat in the tumor is usually less than that of adrenal myelolipoma. In our case, the tumor contained more fat than the 'typical' retroperitoneal teratoma, which led to the misdiagnosis. PMID- 11211807 TI - [Surgical removal of renal cell carcinoma after partial splenic embolization in a patient with liver cirrhosis: a case report]. AB - Partial splenic embolization is used to treat patients with liver cirrhosis accompanied by hypersplenism for improving thrombocytopenia and leukopenia. We report a case in which partial splenic embolization was used before nephrectomy because both renal cell carcinoma and liver cirrhosis were present. A 75-year-old woman visited our hospital complaining of abdominal distension. Computed tomography revealed a 5.5 cm left renal tumor. Liver cirrhosis, ascitis, splenomegaly was observed. Blood tests revealed pancytopenia; platelet count was 2.9 x 10(4)/mm3. The patient was treated by partial splenic embolization in an attempt to ensure a safe nephrectomy. After the embolization, her platelet count increased immediately to 19.2 x 10(4)/mm3, and left nephrectomy was performed successfully. PMID- 11211808 TI - [Papillary renal cell carcinoma complicated with emphysematous pyelonephritis: a case report]. AB - A case of papillary renal cell carcinoma complicated with emphysematous pyelonephritis is reported. A 75-year-old woman with diabetes mellitus was admitted to our hospital with macroscopic hematuria and a child's head-sized firm mass in the left hypochondrium. Computed tomographic (CT) scanning revealed a huge left renal tumor with hydronephrosis. The patient had acute pyelonephritis and antibacterial therapy was initiated. Ten days later, conservative therapy was not effective and CT scan revealed emphysematous necrotic tissue in the tumor. We performed percutaneous drainage. Then dark red liquid and gas were discharged. Her general condition was improving. Left radical nephrectomy was performed. The mass was solid and pathological diagnosis was papillary renal cell carcinoma with necrotic tissue and coated by a thick pseudocapsule. She has remained free of disease for 27 months after operation. PMID- 11211809 TI - [Right ureteral stenosis due to endometriosis occurring in the residual appendix: report of a case]. AB - A 48-year-old female was found to have right flank pain at another hospital and transabdominal ultrasonography showed right hydronephrosis. She was referred to our department for further examination. She had undergone right oophorectomy and total hysterectomy 3 years before. Intravenous pyelography showed right hydronephrosis and retrograde pyelography revealed ureteral stenosis at the lower portion of the right ureter. Endometriosis had developed at the site of previous surgery on the appendix. A mass was formed in an extensive area including the endometriotic lesion, due to adhesion following previous surgery or other reasons, and extended to the retroperitoneum, thereby inducing right ureteral stenosis. The postoperative course was uneventful. The pathological diagnosis was endometriosis of the residual appendix. PMID- 11211810 TI - [A case of traumatic priapism]. AB - We report a case of high flow priapism secondary to arteriovenous fistula produced by perineal trauma in a 43-year-old patient. Diagnosis was based on the result of gasometry in cavernous blood and color doppler sonography. Superselective embolization of the deep artery of the penis was performed with good results. After 6 months of treatment, erection and sexual function were normal. Our case demonstrates that this procedure is a safe and effective therapy for high flow priapism. PMID- 11211811 TI - [A case of polypoid form of parameatal urethral cyst]. AB - A 45-year-old man first noticed a soft tumor on his left lip of the urethral meatus at the age of 15. The lesion had gradually been increasing in size during the last 10 years. He presented to our clinic with division of urinary stream which had been persisting for about nine months. The tumor was resected, and histopathological examination revealed that it was a mucous cyst. The cyst had an outer wall of stratified squamous epithelium and an inner wall of stratified columnar epithelium. Since the inner wall was covered with epithelium originating from the urethral mucosa and the lesion was located outside the urethral meatus, a diagnosis of parameatal urethral cyst was made. Recently, parameatal urethral cyst has rarely been reported since it is often clinically in significant and remains asymptomatic. In our patient, the tumor showed polyploid growth and caused difficulty in urination. The mechanism of its development is considered based on a review of the literature. PMID- 11211812 TI - Acute epididymo-orchitis with abscess formation due to Pseudomonas aeruginosa: report of 3 cases. AB - We report 3 patients with acute epididymo-orchitis with abscess formation due to Pseudomonas aeruginosa, which is relatively unusual and difficult to treat. All patients presented with swollen testicles, pain and high fever. First, they were treated empirically with several antibiotics. After several weeks of antibiotics therapy, the swelling of scrotum still persisted. In one patient, dark yellow pus drained from a fistula of the scrotum. Finally, an orchiectomy was performed on all patients. During the operation, an abscess was found in each testis. Each culture of the pus yielded P. aeruginosa, which is susceptible to many antibiotics. PMID- 11211813 TI - [Leiomyosarcoma of the scrotum: a case report]. AB - Leiomyosarcoma of the scrotum is a rare tumor. Up to 1999, only 29 cases have been reported in the literature worldwide. A 27-year-old man presented with a mass on the left side of the scrotum which had been painless and had gradually enlarged over the previous 10 years. During the following 3 months, however, it became painful and he was then referred to our hospital. Physical examination revealed a solid mass on the left side of the scrotum, measuring 7 cm in diameter, which was not adhering to the testis or to the vas deferens. The tumor was surgically resected. The histological examination confirmed the diagnosis of well differentiated leiomyosarcoma. Adjuvant therapy was considered unnecessary. The follow-up at 41 months revealed no local recurrence or distant metastasis. PMID- 11211814 TI - [The clinical statistics of the operations at the Department of Urology, Tokatsu Hospital: from 1994 to 1999]. AB - We investigated the clinical statistics of the operations and inpatients since the establishment of the department in June 1994 up to May 1999. The total number of inpatients was 1,269 (1,047 males and 222 females), and a total of 1,098 operations were performed. Extracorporeal shock wave lithotriopy (ESWL) was also introduced in 1997, and in addition, it seemed that the number of operations and inpatients would be increasing in future. PMID- 11211815 TI - [Studies on adsorption of the organic phosphorus pesticide with the macroporous resin]. AB - Macroporous adsorbing resins prepared by styrene are selected as absorbent in the static and dynamic adsorption experiments of organic phosphorus pesticide. These resins are attempted to be applied in blood purification to detoxify and save the patient's life. PMID- 11211816 TI - [In vitro dissolution study on the hydroxyapatite biocoatings]. AB - This paper has studied the dissolution behavior of the plasma sprayed and electrochemically prepared hydroxyapatite(HA) biocoatings in the simulated body fluid. XRD and SEM show that the plasma sprayed coating and post-heat treated HA coatings are more soluble, and CaO and alpha-TCP in the coatings gradually disappear and CaCO3 forms during the immersion. The composition of the electrocrystallized and alkaline-treated HA coatings is basically unchanged, and the coatings are more stable in the simulated body fluid. PMID- 11211817 TI - [The effect of polylactide screws on fracture healing]. AB - This experiment aimed at investigating the effect of a kind of home-bred poly-DL lactide screws on fracture healing. An operation was performed so as to make bilateral lateral condylar fractures of the femur in 8 dogs. The left sides were fixed with 2 home-bred PDLLA(Mv = 43 x 10(4)) screws, and the contralateral sides were fixed with 2 metalic screws to be used as controls. The animals were sacrificed at 2, 4, 8, and 12 weeks after surgery. Optic microscopy and SEM photography were done. The results of optic microscopy showed that fibrous callus formed already in both groups by 2 weeks after surgery, and bilateral fractures united uneventfully by 12 weeks. Although the course of fracture healing in experimental group was slower than that in control group, the osteogenesis in experimental group appeared to be normal. The SEM examination demonstrated that collagenous fibers arranged regularly and calcified normally in both groups at 12 weeks. And many square and rhomboid granules produced from the degradation of PDLLA material were found in experimental group at 12 weeks. Therefore, it is suggested that this kind of home-bred PDLLA screws should be applicable to fractures where the tissues are rich in blood supply. PMID- 11211819 TI - [The adsorption on attapulgite and cross-linked agar beads entrapped attapulgite(CAA)]. AB - The adsorption of four drugs with certain toxicity, i.e. chlorpromazine, quinidine, diazepam and phenobarbital on attapulgite and Cross-linked Agar Beads Entrapped Attapulgite(CAA) was determined in this study. The results revealed that attapulgite possessed high adsorption for the cation drugs(chlorpromazine and quinidine), moderate adsorption for diazepam, and slight adsorption for phenobabital. The adsorption in attapulgite was quite quick and came to equilibrium in about 30 min. No significant difference(P > 0.05) of adsorption on attapulgite was observed at 30 min and 60 min. The adsorbent selectivity on CAA was the same as that on attapulgite. The speed of the adsorption was slower on CAA than on attapulgite, but the quantity adsorpted on CAA and that on attapulgite had no marked difference(P > 0.05) after 60 min. CAA preserved the adsorption property of attapulgite fundamentally. CAA overcame the dispersibility of attapulgite distinctly and showed good hemocompatibility and a fair blood flow rate in hemoperfusion. It may play an important role in the separation of blood components and in hemopurification. PMID- 11211818 TI - [Study on the biocompatibility and toxicology of biomaterials--poly(epsilon caprolactone)]. AB - Four observation indexes were selected to evaluate the biocompatibility and toxicology of biodegradable materials poly(epsilon-caprolactone)(PCL), which is synthesized in our laboratory using Ti(OBu)4 as an initiator. The results showed that PCL films had a mild inflammatory reaction in the early days of planting and after 3 months the inflammation basically disappeared. We conclude that PCL material possesses good biocompatibility and has a good developmental prospect. PMID- 11211820 TI - [In vitro study of C3a des Arg produced by plasma incubation with blood purification materials]. AB - This study was performed to evaluate the degree of complement C3 activation of five biomedical polymers (cellulose acetate (CA), polymethylmethacrylate (PMMA), polysulphone (PS), polyethersulphone (PES), sulphonated polyethersulphone(PES SO3) which are used to make hemofilters. The concentration of the activation derivative C3a des Arg was measured by radioimmunoassay (RIA) in human plasma after incubation with these five polymers for 30, 60, 90 and 120 minutes. The experimental results indicated that the presence of polymers caused an increase in C3a des Arg. The potential to activate complement C3 decreased in sequence of CA, PMMA, PES, PS and PES-SO3. CA activated the most complement C3. PES-SO3 activated the least complement C3, and the concentration of C3a des Arg decreased with the increase in sulphonation degree. The investigation demonstrates that with good biocompatibility PES is a promising material to make biocompatible hemofilters. Furthermore, it indicates that PES containing sulphonate groups can achieve a marked reduction in complement activation and supports the sulphonation as a means of improving the biocompatibility of PES for blood purification application. RIA is a reliable and precise quantitative determination of human C3a des Arg and is suitable for testing the activation of complement of various synthetic materials that are utilized or to be utilized in the medical field. PMID- 11211821 TI - [Effects of adhesive proteins on endothelialization of PC crosslinking yak pericardial materials--an experimental study]. AB - To investigate the conditions of endothelialization of biomaterials, we examined in vitro the growth properties of endothelial cells on PC treated yak pericardial materials. After rinsed in normal saline (0.9%), the surface of PC crosslinking yak pericardial materials was precoated with three kinds of adhesive proteins- Laminin (La), Fibronectin(FN) and Collagen-I(CL-I). Ednothelial cells(EC) from the canine were seeded on the precoated materials, and on the uncoated materials as control. The result showed that in the La and FN groups the seeded EC survived and grew on the patches, while in the CL-I group and uncoated group the seeded EC on and around the patches did not continue to live. Conclusively, in this experiment, PC yak pericardial materials had cytotoxicity; the cytotoxicity of PC crosslinking yak pericardial materials could be decreased by La and FN precoating; La and FN promoted the adhesion and growth of EC on the PC yak pericardial materials patches; the materials met the needs of endothelialization in vitro, prominently in the La group; there was significant difference in endothelialization between La and FN groups (P < 0.05); CL-I had no part in promoting EC adhesion and growth. PMID- 11211823 TI - [The construction and physical-mechanical characterization of polymer foams of D. L-PLA]. AB - This study was intended to construct biogradable polymer foam used in tissue engineering. The D. L-PLA was supplied by chengdu institute of organic chemistry. Biogradable polymer membranes were prepared with a novel solvent-casting particulate-leaching technique, then, the constituent membranes with the proper order were laminated to produce three-dimensional foams with continuous pore structure and morphology. Afterwards, the physical-mechanical property of polymer foams were tested. The test results indicated that the lamination process did not change the physical-mechanical property of the polymer membranes. PMID- 11211822 TI - [Cytocompatible evaluation for skin reproducing membrane of medical fibroin]. AB - This study was intended to evaluate the cytocompatibility of skin reproducing membrane of medical fibroin. Cell growth rate test and hemolysis test were conducted to investigate the cytotoxicity and hemolysis reaction for skin reproducing membrane. The results showed there was no obvious cytotoxicity for this kind of membrance. The hemolysis rate was 1.15%. In conclusion, skin reproducing membrane is a material of good cytocompatibility. PMID- 11211824 TI - [The effect of adding cefobid upon the physiochemical properties of calcium phosphate cement]. AB - This study was conducted to analyze the physiochemical properties of different mass ratio compounds of cefobid-load calcium phosphate cement(CPC). The compounds of 0%, 2.9%, 4.8% and 7.4% mass ratio cefobid-load CPC were made respectively. The setting time was observed; the compressive strength of compounds was measured by a material testing machine; the construction of compounds was observed by scanning electron microscopy(SEM) and analyzed by EIG. The results showed that both the setting time and the ratio of hole did not change obviously after the addition of cefobid, but the ultimate compressive strength decreased slowly and the results of the four groups were (21.98 +/- 1.06)MPa, (21.38 +/- 0.95)MPa, (19.22 +/- 1.11)MPa and (13.5 +/- 1.65)MPa respectively. These data indicate there is no obvious effect on the physicochemical properties of calcium phosphate cement after the addition of cefobid between 0% and 4.8%. The compounds have irregular holes and hence a good ability of compressive strength. It might be a new bone grafting material for the reparation of infection-related bone defects. PMID- 11211825 TI - [Three-dimensional finite element analyses on the transtibial residual limb and its prosthetic socket]. AB - This paper presents a method for developing a nonlinear finite element model to analyze the load transfer between the transtibial residual limb and its prosthetic socket. The model was developed on the basis of three-dimensional geometry of the residual limb, internal skeleton, soft liner and socket. Interface elements, were used to connect the skin and the liner to simulate the friction/slip boundary conditions. The analyses were performed in two steps to simulate the donning procedure and the load-bearing situation. The model can be used to predict the pressures, shear stresses and slip between the residual limb and its socket under different external loads. Four models with different degrees of socket rectifications were analyzed. PMID- 11211826 TI - [Recent advance in studies of new intraaortic axial flow pump: "dynamic aortic valve"]. AB - We have previously proposed and demonstrated the feasibility of a new concept of intraaortic axial flow blood pump, termed "Dynamic Aortic Valve(DAV)". Implanted in the position of aortic valve, DAV can serve as either an assistant pump or a mechanical valve subjected to the power input. It has several merits over the traditional axial blood pumps: (1) better anatomic compatibility and biologic compatibility; (2) little foreign material is to be introduced into the corporeality; (3) better resistance to infection; (4) puncturing power line could be eliminated; (5) promoting the failing heart to recovery; (6) simpler structure and better durability. In our recent studies, the structure of DAV is further simplified and performance improved greatly. The structure of DAV is merely an impeller fixed to a magnetic rotor while held by a central shaft hanging from a rigid supporting cage. The rotor-impeller can be driven by an alternative magnetic field derived from a remote magnet, implying that the magnetic source can even be arranged extracorporeally. The DAV can be driven by a rotational magnet placed at a distance of 60 mm. At the state of maximal output of hydraulic power, the flow rate (FR) generated by DAV reaches 5 L/min against an afterload of 70 mmHg(1 mmHg = 0.133 KPa). The maximal pressure differential (PD) maintained by DAV is 131 mmHg. The results further revealed the feasibility of the concept of DAV. PMID- 11211827 TI - [Mechanical mechanism in plastic stage of fracture union--application of bone surface remodeling theory]. AB - In this paper is presented a discussion on the mechanical mechanism in the plastic stage of fracture union. We adopt the bone surface remodeling theory in conjunction with finite element method, choose the strain energy density as mechanical stimulus, work at a three-dimensional finite element model, and then we investigate the mechanical mechanism in the plastic stage of fracture union in three types: exterior osteotylus, interior bony defect and exterior bony defect, using long bone surface remodeling software "BRSS97" we design. The results show that osteotylus can be completely absorbed, and bony defect can recover. For all the three types, the final bone configuration resembles normal state bone configuration. It proves that long bone configuration in the plastic stage of fracture union is the result of the adaptation of bone to loading environment. PMID- 11211828 TI - [Different flow augmentations in coronary, carotid and renal arteries with ECP in experimental canines]. AB - Different flow augmentations were found in canine's coronary, carotid and renal arteries with ECP because of their different anatomical locations in aorta. We used the Electromagnetic Blood Flowmeters to measure the blood flow pre-ECP and during ECP. The results showed ECP increased the diastolic flow of coronary, carotid and renal arteries by 24.48% +/- 1.29%, 27.18% +/- 0.94% and 20.68% +/- 0.80% respectively, decreased their systolic flow by 4.77% +/- 0.48%, 6.45% +/- 0.99% and 9.60% +/- 0.70%, but augmented their mean flow by 18.24% +/- 2.01%, 19.38% +/- 1.47% and 8.42% +/- 0.94% respectively in experimental dogs. These data demonstrate that ECP can greatly increase the mean flow of coronary and carotid arteries but at the same time patently decrease the systolic flow of renal artery. PMID- 11211829 TI - [Effects of stress level on the biomechanical behavior of the temporomandibular joint disc in domestic pigs]. AB - This study aimed to examine the responses of the temporomandibular joint (TMJ) disc against compression, to clarify the property of viscoelasticity and permeability of the disc, and to provide experimental data for further analyzing the mechanism of stress dissipation within the TMJ disc. With the use of confined compression mechanics and biphasic theory, creep experiments on eight TMJ discs of four domestic pigs were performed under three stress levels(0.07 MPa, 0.13 MPa and 0.30 MPa). The results showed that at 0.07 stress level, the compressive stiffness at 2 seconds of the anterior band(AB), intermediate zone(IZ) and posterior band(PB) of the disc was 4.48 MPa, 3.93 MPa and 6.31 MPa, respectively; the coefficient K of permeability was 0.272 x 10(-12) m4/NS, 0.30 x 10(-12) m4/NS, and 0.042 x 10(-12) m4/NS. At 0.30 Mpa level, the compressive stiffness increased to 14.07 MPa, 13.68 Mpa and 14.00 MPa; the coefficient K lowered to 0.017 x 10(-12) m4/NS, 0.012 x 10(-12) m4/NS and 0.005 x 10(-12) m4/NS. In conclusion, the TMJ disc has viscoelastic and biobiphasic properties against compression. The stiffness of the disc increases with the increment of stress level but the coefficient of permeability decreases. These findings demonstrate that the modulation of stress and of permeability may be two important factors influencing stress dissipation and shock absorption behavior of the disc during compressive and impact loads. PMID- 11211830 TI - [The design and comparative biomechanical study of TDP&CS]. AB - A new internal fixation device(TDP&CS) for subtrochanteric fracture of the femurs was designd and compared with Gamma nail and Jewwet nail biomechanically. A model with 5 mm bone deficit presenting as fracture fixation (mFF) and a model with nail holes presenting as fracture healed and nails removed(mFHNR) were designed. Four-point anti-bent test, anti-axial compression test and anti-torsion test were continually performed on mFF, and four-point anti-bent and anti-torsion tests were performed on mFHNR. The results showed that in mFF group, TDP&CS was stronger than Jewwet nail(P < 0.05) in all the three tests, but it was not statistically different from Gamma nail. In mFHNR group, TDP&CS had better features than Gamma nail and Jewett nail in anti-bent and anti-torsion tests (P < 0.05). These data indicate that TDP&CS is a good internal fixation device for subtrochanteric fracture of the femurs, it is as good as Gamma nail and better than Jewett nail in fixing the fracture, and its nail holes could do less injury to the bone as compared with those of the Gamma nail and Jewett nail. PMID- 11211831 TI - [Analysis of impulse response of rectangular ultrasound transducer]. AB - A new expression for calculating the impulse response of rectangular pistonlike transducers, proper to any points of acoustic field, is presented. The radiated field of ultrasound transducer can be analyzed using impulse response method, avoiding paraxial and farfield approximation. The velocity potential at an observation point is expressed as the convolution of the excitation velocity and the impulse response. A time-amplitude shift method for the far field impulse response of small aperture transducers is presented. The radiated field of rectangular transducers is calculated through the new method and the previous method and excellent agreement is observed. PMID- 11211832 TI - [Study on statistical method of distribution for erythrocyte morphological features by computerized image processing]. AB - This study sought to develop a new statistic method for the semiautomatic analysis and classification of erythrocyte morphology based on the morphological features and shape analysis of erythrocytes by computer image processing. Shape factor as the description of the erythrocyte morphological features was used for the shape classification of erythrocytes. And the models and algorithms of erythrocytes image segmentation, cell body shape recognition and measure can be implemented through the VC++. The present method can efficiently and semi automatically provide the statistical analysis of erythrocyte morphology, and can give the distribution of erythrocyte morphological features. The result showed that there was a significant difference between the distribution curves of the normal erythrocyte morphology (one apex) and hemolytic anemia's (two apices). By this way, it can be obtained the proportion data of different cell bodies' shapes. This method could provide some information for the study and diagnosis of the diseases (e.g. hemolytic anemia, pre-leukemia) related to erythrocyte morphology. PMID- 11211833 TI - [A quantitative study of poincare dispersed-dot plot for heart rate variability]. AB - Poincare dispersed-dot plot is an important nonlinear dynamics method that can effectively describe the attractor shape. Yet studies in the past generally processed the plot in a graphic mode without further discussion on the quantitative indices. That was not suited for clinical application and studies. So, based on the shape of Poincare dispersed-dot plot, we propose a group of quantitative parameters of Poincare dispersed-dot plot: plot square(SQ), long axis (LA), short axis(SA), and angle related to long-axis and short-axis(ALS). According to the characters of the heart rate Poincare dispersed-dot plot, we have posed the 'tortoise crawling and counting' algorithm to get these four quantitative parameters. We have tested these four quantitative parameters with clinical and animal experiment data. The results demonstrate that these four parameters are of certain specificity to heart diseases, indicating that these parameters might be useful for clinical diagnosis. PMID- 11211834 TI - [Matching of brain sections based on fourier descriptors]. AB - We developed an algorithm based on Fourier Descriptors(FD) to match brain sections and specially aimed to pool electro-physiological data from individual animals and composite the results on a single brain. To test this algorithm, curvilinear features were first extracted from each section image of the midbrain of the rat resulting in three closed boundaries. A set of boundaries of 38 consecutive sections was then taken as standard templates for matching with any other brain sections processed in a similar way. Each section was represented by Fourier descriptors of these boundaries. Matching was done by minimizing the similarity function between an experimental brain section and the set of standard templates. This algorithm has been successfully used for the study of functional organization of AM-sound sensitive auditory neurons in the midbrain. PMID- 11211835 TI - [Analysis of ultrasonic backscattering microstructure feature of human spleen based on "WD cepstrum"]. AB - A new method "WD cepstrum" for analysing ultrasonic scattered signals based on wavelets decomposition before cepstrum has been developed and then applied to process the backscattered signals of normal and pathological human spleen in vitro. The mean scatterer spacing(MSS) has been estimated. The results show that the MSS data of the two tissues are quite different and "WD cepstrum" is more effective for reflecting the microstructure feature of tissue. The results also illustrate that "WD cepstrum" is an effective method for signal analysis of ultrasonic scattering and characterization of tissue scatterers. PMID- 11211836 TI - [Study of the correlation between in vitro and in vivo evaluation methods on biomaterials--DNA test and muscular implant test]. AB - With the wide-spread use of biomaterials, the safety evaluation on biomaterials has become a very important step. This study on the correlation between DNA test and muscular implant test was done for finding out good in vitro evaluation method. The tissue toxicities of seven biomaterials were examined. Good correlation between DNA test and muscular implant test was demonstrated by Spearman sequential correlation analysis. PMID- 11211837 TI - [The multimedia molecular biological image processing system]. AB - With the use of computer image processing technology and molecular biological technology, we have developed a new multimedia molecular biological information processing system to detect the characteristic parameter of molecular biological electrophoresis image. The system can determine the macromolecules densities and molecular weight of the DNA amplified fragment or restriction endonuclease hydrolytic fragment protein and other macromolecules. The clinical use and biological application indicate that the system is useful to gene diagnosis and molecular biological researches. PMID- 11211838 TI - [An approach to achieve classification of QRS waves with wavelet multiresolution analysis and fractal dimension]. AB - This paper discussed the theoretical analysis of multiresolution ECGs decomposition and expounds the calculation of the fractal dimension. Based on Mallat's multiresolution analysis and fractal dimension of the series, a new approach to classify the QRS complex was provided: the QRS complex was decomposed with a quadratic spline wavelet. At scale 4, the fractal dimension of the decomposed series was calculated, the values of modulus maxima of wavelet transform and the fractal dimension were used as discriminatory criteria to classify QRS. The method was simple and had high anti-noise ability. PMID- 11211839 TI - [The research advance of brain derived neurotrophic factor]. AB - Recent research advances in neuroscience show that neurotrophic factors are proteins that affect selectively various kinds of neurons of CNS and PNS. Brain derived neurotrophic factor (BDNF) is another neurotrophic factor that was first reported by Barde, a German chemist, thirty years later after the nerve growth factor had been found out. BDNF plays an important role in the growth, development, differentiation, maintenance and regeneration of various types of neurons in the CNS and has potential application to the treatment of brain injury and neurodegenerative diseases such as Alzheimer's disease, Parkinson's syndrome, Huntington's chorea and amyotrophic lateral sclerosis. In this paper, the structure, function and potential clinical application of BDNF were reviewed. PMID- 11211840 TI - [Pharmacologic stress myocardial perfusion imaging]. AB - This paper expounds the imaging methods, mechanism of action, hemodynamic responses, efficacy and side effects of three pharmacologic stressors (dipyridamole, adenosine and dobutamine) for clinical use in experiment of diagnosis, thus providing vital reference materials for clinical pharmacologic stress myocardial perfusion imaging. PMID- 11211841 TI - [Optimizing design in tissue engineering]. AB - Tissue engineering may provide an alternative to organ transplantation and tissue transplantation which are both suffering from the limited condition of supply, so it is one of the research high-lights. This article puts forward the viewpoint of optimizing design according to its components and makes relevant suggestion; the aim is to lay a foundation for tissue engineering. PMID- 11211842 TI - [The advance of research for technique of fusing physiological information]. AB - With the increase of human life's pace and people's psychological burden, the spectrum of morbidities changed, and the dynamic disease which is caused by the maladjustment between heart and body becomes the main menace to human being. Through fusing various physiological information, dynamic disease can be diagnosed effectively. The paper discussed the principle of analyzing physiological system's dynamic property and evaluating dynamically human body's health level. It emphasized on introducing the progress of foreign research, and analyzed briefly the problems needed to be dealt with and the future resrarch direction of this field. PMID- 11211843 TI - [The design of axial flow pump]. AB - Axial flow pump has been the hot point of the research field of circulatory support. This article has outlined the basic principle of its design and the methodology of its experimental study, and explained that excellent engineer design, avoiding turbulence, cavitation and wake, and reducing the destroy of red blood cells were the goal to get in design process. The computer-supported design and virtual experiment offered the high efficient tool for the above design. The axial pump has a broad scope in future clinical application. PMID- 11211844 TI - [The realization methods of 3D ultrasonic blood flow mapping]. AB - 3D ultrasonic blood flow mapping has undergone significant technological refinements in image acquisition, signal processing and display techniques since its introduction in 1982. This paper describes the realization methods of 3D ultrasonic blood flow mapping systems. The performances of different systems are evaluated from the views of 3D localization, design of wall filters, velocity estimation and 3D visualization. PMID- 11211845 TI - [A system of microcomputer analysis for biological oxygen consumption and its application]. AB - This paper introduces a microcomputer system of data analysis and methods of measuring oxygen consumption for biological materials. The system overcame some disadvantages of operating inconvenience and difficulties of collective and analytic data by traditional means. The system possesses functions of automatic enactment, collection, save/take and analysis for many experimental data. It can be used to measure oxygen consumption of tissues, cells and mitochondria. PMID- 11211846 TI - [Stress-corrosion test of TIG welded CP-Ti]. AB - In this study TIG (Tungsten Inert Gas) welded CP-Ti were subjected to stress corrosion test under 261 MPa in artificial saliva of 37 degrees C for 3 months. No significant difference was noted on mechanical test (P > 0.05). No color changed and no micro-crack on the sample's surface yet. These results indicate that TIG welded CP-Ti offers excellent resistance to stress corrosion. PMID- 11211847 TI - [Construction and nucleotide sequence assay of human anti-HBs variable region single-chain antibody gene]. AB - The VH and Vk gene which were acquired using phage display technology have been combined by a linker encoding a flexible peptide (Gly4 Ser)3 to form a single chain. Its nucleotide sequence was assayed after cloning the scFv gene into middle plasmid. The successful construction of single-chain gene lays the foundations for the subsequent expression and production of double functional antibody. PMID- 11211848 TI - [Electron spin resonance studies on inhibiting methemoglobin in erythrocyte with exogenous ascorbic acid]. AB - Research on inhibiting the methemoglobin (MetHb) in erythrocyte by means of exogenous ascorbic acid is helpful to elucidating whether exogenous antioxidant inhibits the oxidative denaturation of hemoglobin when the erythrocyte does not inhibit such denaturation with its own antioxidation system. Using electron spin resonance (ESR) technique, we have studied the oxidative denaturation of hemoglobin and the inhibition of MetHb in erythrocyte with the exogenous ascorbic acid. The results indicate that there is the ESR absorption of high spin MetHb (g = 6) at the 5th, 35th and 90th min after the blood was mixed with NaNO2. The ESR absorption of high spin MetHb increases with time. Yet, in the case where the blood was mixed with exogenous ascorbic acid in advance, the ESR absortpion of high spin MetHb (g = 6) only appears at the 35th min among the ESR measures at the 5th, 35th, and 90th min after the blood was mixed with NaNO2. These findings suggest that exogenous antioxidant can inhibit the oxidative denaturation of hemoglobin when the erythrocyte does not inhibit such dematuration with its own antioxidation system. PMID- 11211849 TI - Systemic lupus erythematosus: women's health issues. PMID- 11211850 TI - The stability of and intercorrelations among cardiovascular, immune, endocrine, and psychological reactivity. AB - One hundred fifteen college students were exposed to an evaluative speech task twice, separated by 2 weeks. At both sessions, we assessed cardiovascular, endocrine, immune, and psychological response at baseline and during the task. We found stability across sessions for stress-induced increases in anxiety and task engagement, heart rate, blood pressure, norepinephrine (but not epinephrine), cortisol, natural killer cell cytotoxicity, and numbers of circulating CD3+, CD8+, and CD56+ (but not CD4+ or CD19+) lymphocytes. The stable cardiovascular, immune, and endocrine reactivities were intercorrelated, providing evidence of a unified physiological stress response across these outcomes. Although stable stress-induced increases in task engagement were associated with the physiological stress responses, stress-induced anxiety was not. PMID- 11211851 TI - Review of the treatment literature for encopresis, functional constipation, and stool-toileting refusal. AB - This review summarizes the literature on randomized, controlled, published studies involving medical, behavioral, psychological, and biofeedback treatments for encopresis/functional constipation and stool-toileting refusal in preschool age and school-age children. Nine such studies were located in the literature involving school-age children. No randomized, controlled treatment studies involving preschool-age children have been published. This review revealed no evidence to support the routine use of psychotherapy or anal sphincter biofeedback in the treatment of pediatric fecal elimination dysfunctions, beyond those benefits derived from a comprehensive medical-behavioral intervention. Further, this review indicated that paradoxical constriction of the External Anal Sphincter does not influence the treatment outcome of either biofeedback or medical-behavioral interventions. There are remarkably few controlled treatment outcome studies in this most important clinical area. More research is needed that employs standard treatment outcome variables. PMID- 11211852 TI - Why do we have IgE-mediated immediate hypersensitivity? PMID- 11211854 TI - Do you know that there is a museum dedicated to Florence Nightingale in Turkey? PMID- 11211853 TI - [Multidisciplinary orthodontic treatment of adults: apropos of several cases]. AB - Adult orthodontic's treatment requires the intervention of different specialists in order to establish a treatment schedule ensuring an esthetic and a functional result. PMID- 11211855 TI - Debate: Albumin administration should not be avoided. AB - The recent Cochrane report on albumin administration is analysed and criticised on the grounds of clinical methodology, content and interpretation. Although it is naive and illogical to treat hypoalbuminaemia with albumin infusions, a more balanced view on the use of albumin for resuscitation in acute hypovolaemia is necessary. Once the acute phase of critical illness is past, interstitial volume is often expanded causing oedema, with a low plasma volume. We argue for the use of salt-poor albumin solutions in this situation and conclude that, on current evidence, the assertion that albumin should be avoided in all situations is irrational and untenable. PMID- 11211857 TI - Cholecystectomy and bowel function. PMID- 11211856 TI - Debate: Albumin administration should be avoided in the critically ill. AB - The benefit of albumin administration in the critically ill patient is unproven. Epidemiological evidence suggests that there is an increase in death among patients with burns, hypoalbuminaemia, and hypotension treated with human albumin solution (HAS). In critical illness, hypoalbuminaemia is a result of transcapillary leak, decreased synthesis, large volume body fluid losses, and dilution caused by fluid resuscitation. When treating patients with hypoalbuminaemia, efforts must be centred around correction of the underlying disorder rather than reversal of hypoalbuminaemia. Problems with using albumin arise because it is an expensive blood product, and can result in systemic changes that include cardiovascular, haematological, renal, pulmonary, and immunological effects. PMID- 11211858 TI - MALT lymphomas and Helicobacter pylori? PMID- 11211859 TI - Guidelines for the management of iron deficiency anaemia. PMID- 11211861 TI - [Coordination Center for Clinical Study in Mainz--a new impetus for clinical research]. PMID- 11211860 TI - [Pathology of paraneoplastic syndromes of the central and peripheral nervous systems and muscle ]. AB - INTRODUCTION AND DEVELOPMENT: The paraneoplastic neurological syndromes are alterations associated with neoplasias. However, they are not caused by metastases or complications such as infections, vascular disorders, metabolic or nutritional alterations or secondary effect of treatment. The paraneoplastic syndromes are often associated with the creation of autoantibodies against antigens produced by the neoplastia, but also may be against other cells or target molecules of the patient. Sometimes, especially with antibodies directed against cell membrane proteins, there is a close relationship between the antibody and the target organ, as for example antibodies against the acetylcholine receptor in myasthenia gravis. On other occasions, especially when the antigen is intracellular, the mechanism of the autoantibody reaction is not known. Finally, in a third group, the antibody associated with a particular paraneoplastic neurological alteration has not been identified. In this paper we describe the main paraneoplastic neurological pictures and known antibodies, including the molecular aspects and the neoplasias most frequently related to them. PMID- 11211862 TI - Knee pain in a 40-year-old man. PMID- 11211863 TI - New functional aspects of cathepsin D and cathepsin E. AB - Cathepsin D (CD) and cathepsin E are representative lysosomal and nonlysosomal aspartic proteinases, respectively, and play an important role in the degradation of proteins, the generation of bioactive proteins, antigen processing, etc. Recenty, several lines of evidence have suggested the involvement of these two enzymes in the execution of neuronal death pathways induced by aging, transient forebrain ischemia, and excessive stimulation of glutamate receptors with excitotoxins. CD has also been shown to mediate apoptosis induced by various stimuli and p53-dependent tumor suppression. To gain more insight into in vivo functions of CD, mice deficient in this enzyme were generated. The mutant animals showed a progressive atrophy of the intestinal mucosa, a massive destruction of lymphoid organs, and a profound accumulation of ceroid lipofuscin, and developed a phenotype resembling neuronal ceroid lipofucinosis, suggesting that CD is essential for proteolysis of proteins regulating cell growth and tissue homeostasis. It has also been shown that CD molecules secreted from human prostate carcinoma cells are responsible for the generation of angiostatin, a potent endogenous inhibitor of angiogenesis, suggesting its contribution to the prevention of tumor growth and angiogenesis-dependent growth of metastases. Interestingly, pro-CD from human breast carcinoma cells showed a significantly lower angiostatin-generating activity than that from prostate carcinoma cells. Since deglycosylated CD molecules from both carcinoma cells showed a low angiostatin-generating activity, this discrepancy appeared to be attributed to the difference in the carbohydrate structures of CD molecules between the two cell types and to contribute to their potency to prevent tumor growth and metastases. PMID- 11211864 TI - Transglutaminase-dependent modulation of transcription factor Sp1 activity. AB - Modification of transcription factors would result in significant changes in the expression of related genes. Recently, the presence of transglutaminase (TGase) has been reported in nuclei, the biological significances of which have attracted a great concern. In this study, we tested the possibility that nuclear TGase would crosslink and regulate the activity of a glutamine-rich transcription factor Sp1. The addition of purified guinea pig liver TGase increased the binding activity of Sp1 to the target DNA sequence by gel electrophoretic mobility shift assay. The activity of the human p21WAF1 promoter containing six Sp1 binding sites was increased by the cotransfection of the TGase 2 gene, and two Sp1 sites at -82 and -69, relative to the transcription start site, were essential for the increased activity in human renal embryonic 293T cells. The activity of a minimal promoter containing three consensus Sp1 binding sites was increased by co transfection of human TGase 2 gene. The amount of Sp1 protein was increased dramatically in TGase 2-transfected 293T cells and the Sp1 protein itself from HeLa cell nuclear extracts was crosslinked readily by purified TGase at 37 degrees C in the presence of Ca2+. These results suggest that the nuclear TGase might modulate the activity of the Sp1 transcription factor probably via the posttranslational or transcriptional modification of the factor by TGase. PMID- 11211865 TI - Flow cytometric analysis and chromosome sorting of barley (hordeum vulgare L). AB - Flow cytometric analysis was systematically performed to optimize the concentration and duration of hydroxyurea (DNA synthesis inhibitor) and trifluralin (metaphase blocking reagent) treatments for synchronizing the cell cycle and accumulating metaphase chromosomes in barley root tips. A high metaphase index (76.5% in the root tip meristematic area) was routinely achieved. Seedlings of about 1.0-cm length were treated with 1.25 mM hydroxyurea for 14 h to synchronize the root tip meristem cells at the S/G2 phase. After rinsing with hydroxyurea, the seedlings were incubated in a hydroxyurea-free solution for 2 h and were treated with 1 microM trifluralin for 4 h to accumulate mitotic cells in the metaphase. The consistent high metaphase index depended on the uniform germination of seeds prior to treatment. High-quality and high-quantity isolated metaphase chromosomes were suitable for flow cytometric analysis and sorting. Flow karyotypes of barley chromosomes were established via univariate and bivariate analysis. A variation of flow karyotypes was detected among barley lines. Two single chromosome types were identified and sorted. Bivariate analysis showed no variation among barley individual chromosomes in AT and GC content. PMID- 11211866 TI - Interaction of PRK1 receptor-like kinase with a putative elF2B beta-subunit in tobacco. AB - PRK1, a receptor-like kinase that is expressed in pollen, pollen tubes, and ovaries, has been shown to play important roles in pollen development and embryo sac development in Petunia inflata. We have used the kinase domain of PRK1 as a bait in the yeast two-hybrid system to identify PRK1-interacting proteins. The screening resulted in isolation of a cDNA encoding a protein highly homologous to the human and yeast beta-subunit of translation initiation factor 2B (eIF2B beta), which was designated NeIF2Bbeta. eIF2B is a guanine nucleotide exchange protein that functions in the regulation of translation in eukaryotic cells. Deletion mutants of NeIF2Bbeta were analyzed for their interaction with PRK1, and the results suggested that the N-terminal half of NeIF2Bbeta, especially the region between residue 103 and 235, is important for the interaction. This protein association was confirmed by in vitro binding assay of the recombinant NeIF2Bbeta and PRK1 proteins. Despite high sequence homology between NeIF2Bbeta and its yeast counterpart, the NeIF2Bbeta cDNA could not rescue the phenotype of the yeast mutant strain lacking the GCD7 gene encoding eIF2B-beta, when transferred into the mutant strain. PMID- 11211867 TI - Cloning and characterization of a 22 kDa outer-membrane protein (Omp22) from Helicobacter pylori. AB - Helicobacter pylori is a causative agent of gastritis and peptic ulceration in humans. As the first step towards development of a vaccine against H. pylori infection, we have attempted to identify protective antigens. A potential target of vaccine development would be a H. pylori specific protein, which is surface exposed and highly antigenic. We identified a 22 kDa outer-membrane protein (Omp22) from H. pylori, which was highly immunoreactive. By screening a H. pylori genomic DNA library with rabbit anti-H. pylori outer-membrane protein antibodies, the omp22 gene was cloned and 1.4 kb of the nucleotide sequence was determined. One open reading frame, encoding a 179-residue polypeptide, was identified and the amino acid sequence deduced showed homology with peptidoglycan-associated lipoproteins. The sequence was conserved among other H. pylori strains. Omp22 protein is expressed as a precursor polypeptide of 179 residues and undergoes lipid modification and cleavage of an 18 amino acid signal peptide to yield a mature protein. Omp22 protein in H. pylori as well as recombinant Omp22 protein expressed in E. coli was localized into the outer membrane and exposed on the cell surface. Omp22 may have the potential as a target antigen for the development of a H. pylori vaccine. PMID- 11211868 TI - Costimulatory effect of Fas in mouse T lymphocytes. AB - To induce proper immune responses, T lymphocytes require two types of stimuli, antigen-specific and costimulatory signals. Among costimulatory molecules, CD28 engagement promotes the survival and proliferation of both naive and memory T cells. In addition, it is now believed that Fas may play a role in T cell activation in the human system. It is, however, controversial whether Fas can act as a costimulatory signal in the murine system. Thus, we investigated fundamental differences in the capacity to induce proliferation of T cells between Fas and CD28 in mice. Fas-mediated T cell proliferation was observed only with a full mitogenic dose of anti-CD3 antibodies, whereas CD28 engagement was able to enhance T cell proliferation in the presence of a suboptimal level of anti-CD3 antibody. Furthermore, Fas-engaged T cells showed faster response in the upregulation of CD25 and CD69 expression than CD28-engaged ones. Here, we report that Fas might play a role in mature T cell activation in the mouse system through a different mechanism from that in CD28 costimulation. PMID- 11211869 TI - Identification, expression, and nuclear location of murine Mage-b2 protein, a tumor-associated antigen. AB - MAGE-1, which was originally identified by reacting with cytolytic T lymphocytes derived from the blood of melanoma patients, is a member of a gene family consisting of 17 structurally related genes. The MAGE genes are expressed only in the testis among normal tissues and in a number of human tumors of various histological types. Murine MAGE (also called SMAGE or Mage) genes were found in a study aimed at detecting mouse genes homologous to human MAGE genes. However, the biological functions of MAGE and Mage are currently unknown. To understand the biological functions of Mage, in the present study a recombinant SMAGE2 (Mage-b2) protein of 43 kDa was produced and monoclonal antibodies reactive with Mage-b2 protein were generated. One monoclonal antibody, smpG4A, specifically recognized a 43 kDa protein in lysates of Mage-b2 mRNA-positive sarcoma cells and of the testis. Immunohistochemistry showed that Mage-b2 is located in the nucleus of Mage-b2 mRNA-positive sarcoma cells. These results should contribute to understanding the biological functions of Mage. PMID- 11211870 TI - Downregulation of MHC class II expression by oxidant-induced apoptosis in EBV transformed B-cells. AB - The expression of MHC class II molecules is actively regulated upon various cellular stimuli. Since apoptosis is an inducible cellular process, it was asked whether cells undergoing apoptosis would also modulate their expression of class II molecules. Using an EBV-transformed B-cell line, the cell surface expression of HLA-DR molecules was analyzed by fluorescence-activated flow cytometry on normal and oxidant-treated apoptotic cells. A rapid and continuous decrease in HLA-DR expression was observed in apoptotic cells. RNA analysis and semiquantitative RT-PCR of cytoplasmic beta-actin mRNA showed that apoptotic cells contain partially degraded RNA and much lower amounts of beta-actin mRNA. Nevertheless, when compared after normalization of intact mRNA amounts, the HLA DRB mRNA signals were of similar strength in normal and apoptotic cells as determined by semiquantitative RT-PCR. Thus, the decrease in the number of class II molecules during apoptosis underlies no specific program for downregulation of HLA-DRB mRNA transcription but is due to a nonspecific degradation of RNA molecules accompanied by cell death. PMID- 11211871 TI - Gene delivery into rat glomerulus using a mesangial cell vector. AB - To develop an effective protocol of gene transfer into glomeruli, an ex vivo gene delivery system using rat mesangial cells (RMC) as a vector was examined. RMC genetically engineered with a retrovirus harboring the Escherichia coli beta galactosidase gene was used to estimate the efficacy of gene delivery and the location of the cells within the kidney. The RMC expressing beta-galactosidase, RMCLZ1, was cultured in vitro and the cells were injected into the left kidney through the renal artery of a normal Sprague Dawley rat. At least 1 x 10(6) RMCLZ1 was required for effective gene delivery into glomeruli. One hour and 1, 4, and 14 d after injection, glomeruli were isolated from the left kidneys injected with the cells and the expression of beta-galactosidase in each glomeruli was evaluated. One hour and 1 d after injection, more than 90 and 80%, respectively, of glomeruli from the left kidney showed strong beta-galactosidase activity, while no activity of beta-galactosidase was found in the glomeruli from the right kidneys. The number of glomeruli stained by X-gal and the intensity decreased with time. Fourteen days after injection, about 35% of the glomeruli retained the RMCLZ1. X-gal and periodic acid-Schiff staining of frozen sections obtained 14 d after injection allowed the estimation of the site where the mesangial cells injected were located. The mesangial cells were found mainly in two different locations, the glomerular capillary and the mesangium. The majority (about 90%) of the mesangial cells were located in the glomerular capillary and about 9% of the cells were in the mesangial area. Occasionally, the positive staining was found in proximal tubules and the interlobular artery. Although additional methods are required for the site-specific targeting of the mesangial area, the ex vivo gene transfer to glomeruli is feasible and may be a useful tool for future investigations in the pathological mechanisms of glomerular injury. PMID- 11211872 TI - Role of hippocalcin in Ca2+ -induced activation of phospholipase D. AB - The role of hippocalcin as a novel mediator in the PKC-independent Ca2+ -induced phospholipase D (PLD) activation pathway was investigated. Hippocalcin was expressed in the Sf9 insect cell expression system because the myristoylation of this protein is essential for its function. PLD and Cdc42 proteins were prepared from a rat brain cell membrane and cytosol, respectively. The recombinant hippocalcin was expressed in the Sf9 cell using expression vector pVL1393. The hippocalcin expressed was purified as a single band on PAGE following the hydrophobic phenyl HPLC and TSKgel G3000SW gel filtration HPLC. The molecular size of the rat brain hippocalcin expressed in this system was estimated to be 22 kDa. Myristoylated hippocalcin migrated faster than the non-myristoylated form on SDS-PAGE. Less than 10% of the total hippocalcin expressed was myristoylated in this baculovirus expression system. PLD was extracted from rat brain membranes and chromatographically enriched 70-fold. From the rat brain cytosol, Cdc42 was purified to near homogeneity. While hippocalcin alone did not activate PLD, it increased PLD activity activated with Cdc42 1.8-fold in the presence of calcium (300 nM free calcium). In the absence of calcium in the reaction mixture, the effect of hippocalcin to facilitate Cdc42-activated PLD activity was abolished. This result suggests that hippocalcin might be one of the regulatory proteins in the PKC-independent Ca2+ -mediated PLD activation pathway in conjunction with the Cdc42 protein. PMID- 11211873 TI - Isolation and characterization of a class I SLG gene from Chinese cabbage (Brassica campestris). AB - In Brassica species, self-incompatibility in the recognition reaction between self and non-self pollens is determined by two genes, SLG and SRK, at the S locus. We have cloned and characterized a genomic DNA fragment containing a complete open reading frame of the SLG gene from Chinese cabbage. The genomic clone, named BcSLG2, was found to possess the region that shares a homology of 77% in amino acid identity with the SLG46 gene of Brassica campestris. Northern blot analysis revealed that the BcSLG2 gene expression is restricted to the pistil of Chinese cabbage flower. In situ hybridization showed that in the pistil, the gene is expressed predominantly in the stigmatic tissue. Much lower expression in the tapetum was also detectable at an immature stage of the flower development. Southern blot hybridization with the BcSLG2 DNA probe showed polymorphism in the SLG gene organization of the Chinese cabbage plants. These results will provide valuable information in understanding the S gene complex of the Chinese cabbage plants. PMID- 11211874 TI - Expression and characterization of fibroblast growth factor 8 from Mexican axolotl, Ambystoma mexicanum. AB - Fibroblast growth factor (FGF) has been known to regulate the proliferation and differentiation of a variety of cell types via interaction with a specific FGF receptor on the cell surface. In the present study, Fgf8 cDNA of Mexican axolotl, Ambystoma mexicanum, was expressed in Escherichia coli as an MBP-FGF8 fusion protein. The cell proliferation activity of the recombinant FGF8 (rFGF8) was measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazoliumbromide (MTT) assay. The addition of rFGF8 to the culture medium enhanced proliferation of BALB/c 3T3 and BHK21 cells about 1.4-1.5 fold. To analyze the binding activity of rFGF8 to the cell surface, cell surface enzyme linked immunosorbent assay was developed. Comparison of the structure of basic FGF with the computer-simulated structure of FGF8 suggested that Tyr-58, Glu-132, Tyr-139, and Leu-179 might be the potential receptor binding sites. Amino acid substitution muteins of FGF8 were constructed by PCR-derived directed mutagenesis and the muteins were overexpressed in E. coli. The rFGF8 muteins were purified and their binding activities were analyzed. Substitution of Tyr-58 or Glu-132 or Leu-179 of the FGF8 with alanine reduced the binding affinity, while substitution of Tyr-139 with alanine did not alter the binding affinity. These results imply that Tyr-58, Glu-132, and Leu-179 of FGF8 might be involved in its binding to the cell surface. PMID- 11211875 TI - The first successful prenatal diagnosis on a Korean family with citrullinemia. AB - DNA prenatal diagnosis was successfully performed on a family with citrullinemia. The father carried the G324S mutation and the mother carried the IVS6-2A > G mutation in the argininosuccinate synthase gene. They had a previous child with citrullinemia who died in the week after birth owing to complicated hyperammonemia. The lost child turned out to be a compound heterozygote. DNA was extracted from the cultured amniotic cells after amniocentesis done at 18-week gestation. For the detection of the G324S mutation, the PCR and restriction fragment length polymorphism method was used, and for the IVS6-2A > G mutation, allele-specific PCR was performed. The fetus was found to carry G324S but not IVS6-2A > G, suggesting a heterozygote carrier. Pregnancy was continued and a healthy boy was born. Plasma amino acid analysis performed on the third day after birth was normal and the serial ammonia level was in the normal range. A molecular study on his genomic DNA after birth also agreed with the previous fetal DNA analysis. He is now 2-months old with normal growth and development. PMID- 11211876 TI - Dose-dependent selective priming of Th1 and Th2 immune responses is achieved only by an antigen with an affinity over a certain threshold level. AB - Helper CD4+ T lymphocytes can be divided into two subsets, Th1 and Th2. The types of Th subsets activated during the adaptive immune response inductiondetermine the efficacy of immune responses against thee antigens introduced. Selective differentiation of subsets of CD4+ T lymphocytes has been known to be influenced by several factors, such as the cytokine environment around the T cells, the specificity of antigen recognition bythe T cell receptor, the expression of costimulatory molecules, and/ or the dose of the antigen applied to stimulate the T cells. In this study, we tried to determine the influence of the antigen dose on the selective priming of T lymphocytes when an inefficient antigen was applied since all the conclusions drawn from previous experiments were based on experiments with immune systems which responded well against the antigens introduced. When the recombinant hen egg-white lysozyme (HEL) was used too stimulate immune responses in HEL low-responder C57B3L/6 mice, dose-dependent selective priming of immune responses was not observed. However, when the variant antigen, which had been characterized as an efficientantigen in anti-HEL immune response induction in the low-responder mice, was applied, dose-dependent selective priming of Th immune responses was clearly demonstrated. These results suggested that dose-dependent selective priming of Th immune responses could be achieved only by the antigens with an affinity over a certain level. PMID- 11211877 TI - Proteome analysis of light-induced proteins in Synechocystis sp. PCC 6803: identification of proteins separated by 2D-PAGE using N-terminal sequencing and MALDI-TOF MS. AB - The cyanobacterium Synechocystis sp. PCC 6803 is an ideal model organism for the proteome study of light-induced gene expression because the whole genomic sequence has been determined. The soluble proteins extracted from light- and dark cultured cells were separated by two-dimensional polyacrylamide gel electrophoresis. Light-induced protein spots electroblotted on a polyvinyldiene difluoride membrane were analyzed by N-terminal Edman sequence determination and followed by CyanoBase. The tryptic digests of some proteins were also confirmed by matrix-assisted laser desorption ionization/time-of-flight (MALDI-TOF) and MS Fit search. Interestingly, eight proteins were related to photosynthesis and respiration (RbcS/L, CbbA, Gap2, AtpB, CpcB, PsbO, and PsbU). Four proteins (SodB, DnaK, GroEL2, and Tig) were involved in cellular processes and the functions of another two proteins (rehydrin and membrane protein) were unknown. The proteome analysis by N-terminal Edman sequencing and MALDI-TOF enabled us to characterize one-shot protein profiles expressed under different physiological conditions. PMID- 11211878 TI - The Na+ -Ca2+ exchanger is essential for embryonic heart development in mice. AB - The cardiac Na+ -Ca2+ exchanger 1 (NCX1) is thought to be the major calcium extrusion mechanism and to play an important role in the regulation of intracellular calcium in the heart. The Na+ -Ca2+ exchanger is particularly abundant in the heart, although it is found in a variety of other tissues. To investigate the role of NCX1, we have generated NCX1-deficient mice. Mice heterozygous for the NCX1 mutation showed no discernable phenotype, grew normally, and were fertile; however, no viable homozygote was observed among 175 offspring obtained from intercrosses of heterozygotes. All the homozygous mutant mice died in utero before E10.5. Morphological analysis indicated that homozygotes of NCX1 mutation at E9.5 died with an underdeveloped heart with a dilated pericardium. Microscopic analysis of these embryos showed myocardial cell loss due to apoptosis. The apoptosis was first observed in E8.5 mutant heart. Areas outside the heart appeared normal in the mutant embryos at E8.5. In contrast, at E9.0, various regions of mutant embryos showed extensive cell loss. These results suggest that mutant embryos die owing to cardiac abnormalities caused by apoptotic cell loss, indicating that NCX1 is essential for normal development of the heart. PMID- 11211879 TI - Excision repair of 2,5-diaziridinyl-1,4-benzoquinone (DZQ)-DNA adduct by bacterial and mammalian 3-methyladenine-DNA glycosylases. AB - The mechanisms of anticancer activity of 2,5-diaziridinyl-1,4-benzoquinone (DZQ) are believed to involve the alkylation of guanine and adenine bases. In this study, it has been investigated whether bacterial and mammalian 3-methyladenine DNA glycosylases are able to excise DZQ-DNA adduct with a differential substrate specificity. DZQ-induced DNA adduct was first formed in the radiolabeled restriction enzyme DNA fragment, and excision of the DNA adduct was analyzed following treatment with homogeneous 3-methyladenine-DNA glycosylase from E. coli, rat, and human, respectively. Abasic sites generated by DNA glycosylases were cleaved by the associated lyase activity of the E. coli formamidopyrimidine DNA glycosylase. Resolution of cleaved DNA on a sequencing gel with Maxam-Gilbert sequencing reactions showed that DZQ-induced adenine and guanine adducts were very good substrates for bacterial and mammalian enzymes. The E. coli enzyme excises DZQ-induced adenine and guanine adducts with similar efficiency. The rat and human enzymes, however, excise the adenine adduct more efficiently than the guanine adduct. These results suggest that the 3-methyladenine-DNA glycosylases from different origins have differential substrate specificity to release DZQ-DNA lesions. The use of 3-methyladenine-DNA glycosylase incision analysis could possibly be applied to quantify a variety of DNA adducts at the nucleotide level. PMID- 11211880 TI - Efficient intracellular delivery of GFP by homeodomains of Drosophila Fushi tarazu and Engrailed proteins. AB - The 60 amino acid long homeodomain of Antennapedia (Antp), either alone or as a fusion protein with 30-40 amino acid long foreign polypeptides, has been reported to cross biological membranes by an energy- and receptor-protein-independent mechanism. Moreover, the 16 amino acid long third helix of the Antp homeodomain, so-called penetratin, possesses translocation properties when fused to fewer than 100 amino acids as well. These findings led us to study whether such a protein tansduction property is shared by other homeodomains. We report here that homeodomains of two homeoproteins, Fushi-tarazu and Engrailed, are able to transduce a 238 amino acid long green fluorescent protein into cultured cells as efficiently as other well-known protein transduction domains, such as an internal oligopeptide of Tat and penetratin. These findings suggest that such transduction activity of homeodomains might have some physiological roles and that it can be exploited for development of efficient transduction vectors for research use and protein therapy. PMID- 11211881 TI - Identification of novel genes differentially expressed in PMA-induced HL-60 cells using cDNA microarrays. AB - Identification of normal growth and differentiation-inducing proteins and their interaction in normal development have made it possible to elucidate the molecular basis of normal development and the mechanisms uncoupling growth and differentiation during tumor development. The development of cancer and the experimental reversal of tumorigenicity are accompanied by complex changes in patterns of gene expression. cDNA microarrays provide a powerful tool for studying these phenomena. In the present study, a high-density microarray of human cDNA elements was used to search for differences in gene expression associated with differentiation of human promyelic leukemia HL-60 cells. Microarrays containing 3,063 human cDNAs were printed on glass slides with high speed robotics. These DNA 'chips' were used to quantitatively monitor differential expression of the cognate human genes using a highly sensitive two color hybridization assay. The identification of known and novel phorbol ester regulated genes in hematopoietic progenitor cells demonstrates the sensitivity of the assay. PMID- 11211882 TI - My aching back: a serious complaint in children. PMID- 11211883 TI - Clinically challenging mammographic artifacts: a pictorial guide. AB - Artifacts on mammographic images detract from the overall quality of the images and often present clinical and technical troubleshooting difficulties for the interpreting radiologist, technologist, and medical physicist and for the equipment and processor service personnel. This presentation demonstrates several types of mammographic artifacts that may pose a clinical challenge. They are arranged in the following categories: (1) particularly dangerous artifacts, (2) masses, (3) calcifications, (4) density variations, and (5) miscellaneous artifacts. Examples of such findings as summation shadows, normal anatomic variations, and incorrect positioning are also demonstrated as artifacts in this guide, because they may affect image quality or patient radiation dose. Under the Mammography Quality Standards Act, the lead interpreting physician has the responsibility for ensuring that the facility meets quality assurance requirements and is required to follow up with the technologist on poor-quality images. It is vital to recognize and correct for artifacts, whether they simulate non-existent lesions or obscure real pathology, because misinterpretation can lead to undesirable consequences. PMID- 11211884 TI - Decline of hepatitis C virus load in serum during the first 24 h after administration of interferon-beta as a predictor of the efficacy of therapy. AB - BACKGROUND/AIMS: Hepatitis C virus (HCV) kinetics during interferon (IFN)-alpha treatment have been evaluated recently, however, little is known about the resultant viral kinetics in IFN-beta treatment. In this study, we evaluated HCV kinetics during the first 24 h of IFN-beta treatment, and also assessed their relationship to therapeutic outcomes. METHODS: We measured HCV RNA levels at 0 and 24 h after the initiation of IFN-beta treatment, and we calculated the decay slope, viral half-life, and viral production and clearance. Then we analyzed these factors as they related to therapeutic responses with IFN-beta as well as to clinical variables, i.e. genotype, diversity of hyper variable region, and histological findings. RESULTS: Patients with sustained responses (SR) displayed steeper decay slopes of the viral load than those without SR (2.87 +/- 1.41 vs. 1.82 +/- 1.66, P = 0.031). On the other hand, the decay slope was not affected by the clinical variables. The values of viral half-life and viral production and clearance showed no significant correlation to the response and the clinical variables. CONCLUSION: This study demonstrated that the decay slope of the viral load during the first 24 h is related to the virological response to IFN-beta treatment. PMID- 11211885 TI - Inhibition of hepatitis B virus production associated with high levels of intracellular viral DNA intermediates in iron-depleted HepG2.2.15 cells. AB - BACKGROUNDS/AIMS: The effects of iron-depletion on hepatitis B virus (HBV) replication were examined in HepG2.2.15 cells. METHODS: Proliferating cells were iron-depleted with desferrioxamine (DFO), at 20 or 100 microM for 48 h. Levels of viral mRNAs, cytoplasmic DNA replicative intermediates and virion production were examined. A comparative study was performed with hydroxyurea, a specific inhibitor of ribonucleotide reductase. RESULTS: In desferrioxamine treated cells, virion production is dramatically decreased, while viral replicative intermediates accumulate in the cytoplasm. DFO, like hydroxyurea, blocks cell cycle progression in the G1/S transition or S phase with a corresponding 2-fold increase of viral mRNAs. As expected, hydroxyurea leads to a strong reduction of virion production associated with low levels of intracellular replicative intermediates. CONCLUSIONS: These results strongly suggest that iron depletion affects the HBV life cycle indirectly through the cell cycle arrest and directly through the inhibition of the viral DNA secretion. They also indicate the need to re-evaluate with caution the iron depletion protocols on HBV infected patients since a decrease of viral markers in the serum following iron-depletion may not reflect a decrease of viral replicative forms, but on the contrary, could be associated with active viral DNA synthesis. PMID- 11211886 TI - Maintenance of primary murine hepatocyte functions in multicomponent polymer capsules--in vitro cryopreservation studies. AB - BACKGROUND/AIMS: The potential of a new encapsulation system has been evaluated as an artificial housing for liver cells. METHODS: Murine hepatocytes were encapsulated in specially designed multicomponent capsules formed by polyelectrolyte complexation of sodium alginate, cellulose sulphate and poly(methylene-co-guanidine) hydrochloride, the permeability of which has previously been characterised. RESULTS: We demonstrate here the absence of cytotoxicity and the excellent biocompatibility of these capsules towards primary culture of murine hepatocytes. Experimental results demonstrated that the encapsulated hepatocytes retained their specific functions--transaminase activity, urea synthesis and protein secretion--over the first 4 days of culture in minimum medium. The cryopreservation of encapsulated hepatocytes, for periods of up to 4 months, did not alter their functional capacities, as no major differences were observed between unfrozen and frozen encapsulated cells for the functions tested. CONCLUSIONS: Because of the absence of cytotoxicity, and the ease of handling and cryopreservation, while maintaining liver specific functions, the described system appears to be valuable for murine liver cell encapsulation. It is also a promising tool for fundamental research into drug metabolism, intercellular regulation, metabolic pathways, and the establishment of banks for the supply and storage of murine hepatocytes. PMID- 11211887 TI - Duck hepatitis B virus polymerase gene mutants associated with resistance to lamivudine have a decreased replication capacity in vitro and in vivo. AB - BACKGROUND/AIMS: Hepatitis B virus mutants of the polymerase gene are frequently selected during lamivudine therapy for chronic hepatitis B. To study the biology of these mutants, we analyzed their replication capacity in the duck hepatitis B virus (DHBV) infection. METHODS: The B and C domain polymerase mutants corresponding to the clinical isolates were engineered by site directed mutagenesis in the DHBV genome in different expression vectors. RESULTS: The study of the enzymatic activity of the mutated viral polymerase polypeptides analyzed in a cell free system demonstrated a lower priming activity and a decreased capacity of elongation of viral minus strand DNA that was consistent with the lower replication capacity of these mutants in transfected leghorn male hepatoma cells compared to wild type genome. These mutants had a lower replication capacity in primary hepatocytes and in in vivo transfected ducklings. Although resistant to lamivudine, these mutants remained sensitive to PMEA. CONCLUSION: YMDD mutants of the DHBV reverse transcriptase have a decreased replication capacity both in vitro and in vivo, and are not cross-resistant to PMEA. These results may be important to design new antiviral strategies to combat the replication of the lamivudine resistant viral strains. PMID- 11211888 TI - Rapid seroprotection against hepatitis B following the first dose of a Pre-S1/Pre S2/S vaccine. AB - BACKGROUND/AIMS: Will immunization with an experimental Pre-S1/Pre-S2/S hepatitis B vaccine (Bio-Hep-B) induce faster seroprotection using fewer doses as compared with a yeast derived S vaccine (Engerix B). METHODS: Healthy volunteers, n = 36, mean age 23 y, randomized to receive 2 or 3 doses of both vaccines given months 0 and 6, or 0, 1 and 6. RESULTS: Following primary immunization, seroprotection occurred in 6, 39, 53 and 60% in the Bio-Hep-B group at weeks 1, 2, 3 and 4, compared with 0, 12, 18 and 12.5% in the Engerix-B vaccinees, respectively. Six months following injection of the first dose, seroprotection was 70 and 25% in Pre-S/S and S vaccinees respectively. Area under the curve in vaccinees of Bio Hep-B; versus Engerix-B showed mean anti-HBs level of 365 +/- 166 and 85 +/- 48 mIU/ml x day respectively (P = 0.012). At month 7, 100% seroprotection was achieved in both groups while anti-HBs rose from 81 to 28,800 mIU/ml and from 12 to 923 mIU/ml in recipients of Bio-Hep-B and Engerix-B respectively (P < 0.025). CONCLUSIONS: Bio-Hep-B induces rapid seroprotection against hepatitis B in 60-70% of vaccinees, within 4-24 weeks after the first dose. Two instead of the conventional three doses of the Pre-S/S vaccine may be sufficient to induce adequate seroprotection. PMID- 11211889 TI - A randomized, double-blind controlled trial of interferon alpha-2b and ribavirin vs. interferon alpha-2b and amantadine for treatment of chronic hepatitis C non responder to interferon monotherapy. AB - BACKGROUND/AIMS: Interferon-based regimens (alone or with ribavairin) are standard therapies for chronic hepatitis C. The aim of this study was to compare a 24-week regimen of interferon alpha-2b + ribavirin (IFN + RIBA) to interferon alpha-2b + amantadine (IFN + AMANT) in non-responders to previous interferon monotherapy. METHODS: In a multi-center, double-blind clinical trial, 118 patients (non-responders to previous interferon monotherapy) were equally randomized into the two arms: interferon alpha-2b (3 MU thrice weekly) and ribavirin (800 mg daily) vs. interferon alpha-2b (3 MU thrice weekly) and amantadine (200 mg daily). RESULTS: After 24 weeks of therapy, HCV RNA became undetectable in 34.8% (95% CI: 23.7-49.2) of IFN + RIBA and 19.6% (95% CI: 10.6 34.7) of IFN + AMANT (P = 0.10). This response was sustained in 3.9% (95% CI: 1.0 14.9) of IFN + RIBA and 0% of IFN + AMANT (P = 0.16). Ten patients from IFN + AMANT (17%) and 12 patients (20%) from IFN + RIBA were discontinued before completion of therapy. Of these, 7% in IFN + AMANT and 12% in IFN + RIBA were discontinued due to adverse effects. CONCLUSIONS: Re-treatment of interferon non responders with a 24-week course of IFN + AMANT was not associated with any sustained viral eradication. Although IFN + RIBA in this group was associated with a reasonable end of treatment response, relapses were common and sustained responses were low. PMID- 11211890 TI - Schistosomiasis mansoni and viral B hepatitis in woodchucks. AB - BACKGROUND/AIMS: An interaction between human schistosomiasis and viral hepatitis B has often been suggested, but never established. The experimental investigation has been hampered by the lack of a suitable model. Only woodchucks are susceptible to both Schistosoma mansoni and a B-like hepatitis virus (WHV) infections. This study explores the relevance of this unique model regarding hepatitis/schistosomiasis interactions. METHODS: Woodchucks (Marmota monax and Marmota marmota) were infected with: (a), S. mansoni; (b), WHV; or (c), both S. mansoni and WHV. RESULTS: Following the experimental parasitic infection of woodchucks, with or without WHV, schistosomiasis presented a peculiar and severe course in early infection, involving mostly the intestines. Subsequently, the intestinal and hepatic lesions underwent considerable modulation and the periovular granulomas decreased in size and number, while the parasitic infection tended to self-cure within the 9 months following infection. Nine woodchucks inoculated with the hepatitis virus alone presented with several degrees of acute and chronic hepatitis, with one of them dying of hepatocarcinoma 1 year after inoculation. Four woodchucks with concomitant viral and schistosome infections presented with a simple additive pattern of lesions, without any evidence of modification or aggravation of either one of the two infections. Similarly, no significant impact of schistosomiasis on WHV serum markers could be seen. CONCLUSIONS: Schistosomiasis and viral hepatitis in woodchucks run parallel courses, with neither apparent special histological features derived from the association of the two conditions, nor modulation of WHV replication. Schistosomiasis itself, however, was observed to run a peculiar course in the woodchuck. The present data are important for consideration in further experiments exploring the interplay between schistosomiasis and viral hepatitis induced liver damage in this unique experimental host. PMID- 11211891 TI - The effects of interferon alpha-2b in combination with ribavirin on health related quality of life and work productivity. AB - BACKGROUND/AIMS: Interferon plus ribavirin is the most effective therapy for chronic hepatitis C. The aim of this study was to evaluate the effect of chronic hepatitis C and therapy on health-related quality of life and work functioning. METHODS: Nine hundred and twelve patients with hepatitis C infection were randomized in a controlled trial of Interferon alpha 2b 3 MU tiw for 24 or 48 weeks plus ribavirin 1000-1200 mg or placebo. Questionnaire-based assessments of health-related quality of life and work functioning were performed before, during, and after treatment. Outcome measures included the SF-36 Health Survey and additional generic and specific scales. Work functioning was assessed as missed days, shorter hours or less productivity at work. RESULTS: Pre-treatment, patients had significant impairment in five of eight SF-36 concepts compared to matched population norms. Sustained responders had a return to normal for four of these five concepts. Quality of life did not improve in non-responders. Improvements in histology, viral load or ALT values predicted improvements in quality of life. Sustained responders also had improvements in work functioning and productivity. CONCLUSIONS: Hepatitis C patients had impaired quality of life. After combination therapy, sustained virologic responders achieved benefits in their quality of life and work functioning. PMID- 11211892 TI - Bioencapsulated hepatocytes for experimental liver support. PMID- 11211893 TI - Bacterial translocation: cause or consequence of decompensation in cirrhosis? PMID- 11211894 TI - Dendritic cells: regulators of hepatic immunity or tolerance? PMID- 11211895 TI - De novo tumours after liver transplantation in adults. What is the actual risk? PMID- 11211896 TI - The Wilson's disease gene and phenotypic diversity. PMID- 11211897 TI - Images in hepatology. Fistulization of a hepatocellular carcinoma into the duodenum. PMID- 11211898 TI - Orlistat associated subacute hepatic failure. PMID- 11211899 TI - Selective arterial embolization for life threatening hemobilia after transjugular intrahepatic portosystemic shunt placement. PMID- 11211900 TI - Improvement of magnetic resonance spectroscopic abnormalities but not pallidal hyperintensity followed amelioration of hepatic encephalopathy after occlusion of a large spleno-renal shunt. PMID- 11211901 TI - Hepatic undifferentiated embryonal sarcoma: malignant evolution of mesenchymal hamartoma? Study of one case with immunohistochemical and flow cytometric emphasis. PMID- 11211902 TI - Drug biotransformation by human hepatocytes. In vitro/in vivo metabolism by cells from the same donor. AB - BACKGROUND/AIMS: Cultured human hepatocytes are considered a close model to human liver. However, the fact that hepatocytes are placed in a microenvironment that differs from that of the cell in the liver raises the question: to what extent does drug metabolism in vitro reflect that of the liver in vivo? This issue was examined by investigating the in vitro and in vivo metabolism of aceclofenac, an analgesic/anti-inflammatory drug. METHODS: Hepatocytes isolated from programmed liver biopsies were incubated with aceclofenac, and the metabolites formed were investigated by HPLC. During the course of clinical recovery, patients were given the drug, and the metabolites, largely present in the urine, were analyzed. In vitro and in vivo data of the same individual were compared. RESULTS: The relative abundance of oxidized metabolites in vitro (i.e. 4'OH-aceclofenac + 4'OH diclofenac vs. total hydroxylated metabolites; Spearman's p = 0.855), as well the hydrolysis of aceclofenac (4'OH-diclofenac vs. 4'OH-aceclofenac + 4'OH diclofenac; p = 0.691) correlated well with in vivo data. The conjugation of the drug in vitro (24.6 +/- 7.6%) was lower than that in vivo (44.9 +/- 5.3%). The rate of 4'OH-aceclofenac formation in vitro correlated with the amount of metabolites excreted in urine after 16 h (p = 0.95). CONCLUSIONS: The in vitro/in vivo metabolism of the drug was surprisingly similar in each patient. The variability observed in vitro reflected an existing phenotypic variability among donors. PMID- 11211903 TI - Daily variation of azygos and portal blood flow and the effect of propranolol administration once an evening in cirrhotics. AB - BACKGROUND/AIMS: Esophageal variceal bleeding occur more often at night, however, the mechanism for this remains unclear. This study investigated the daily variation of azygos blood flow (AzBF) and portal blood flow (PBF) and the effects of propranolol administration given once in evening in cirrhotics. METHODS: Blood flow were measured using magnetic resonance imaging. Hemodynamic parameters were determined at 08:00, 16:00 24:00 and again 08:00 h, and were measured at baseline and after 14 days oral administration of propranolol (30 mg, n = 7) or placebo (n = 7) at 19:00 h in 14 patients. RESULTS: A daily fluctuation of AzBF and PBF was observed, peaking at 24:00 h in nine patients. In three other patients, peak AzBF and PBF were observed both at 16:00 and 24:00 h. Two patients were constant throughout the day. When the daily variation was compared, ANOVA showed a significant difference (P < 0.001). Propranolol administration at 19:00 h reduced AzBF (-40.7 +/- 17.9% vs. baseline, P < 0.001) and PBF (-26.5 +/- 10.7% vs. baseline, P < 0.01) at 24:00 h. CONCLUSIONS: We found that in most cirrhotics, AzBF and PBF peaks at midnight. Dosing of propranolol in the evening may be important for its role in preventing variceal bleeding. PMID- 11211904 TI - Bacterial translocation of enteric organisms in patients with cirrhosis. AB - BACKGROUND/AIMS: The aim of the study was to investigate the prevalence and associated risk factors for bacterial translocation in patients with cirrhosis, a mechanism involved in the pathogenesis of bacterial infections in experimental cirrhosis. METHODS: Mesenteric lymph nodes were obtained for microbiological culture from 101 patients with cirrhosis and from 35 non-cirrhotic patients. RESULTS: Enteric organisms were grown from mesenteric lymph nodes in 8.6% of non cirrhotic patients. In the 79 cirrhotic patients without selective intestinal decontamination, the prevalence of bacterial translocation significantly increased according to the Child-Pugh classification: 3.4% in Child A, 8.1% in Child B and 30.8% in Child C patients (chi2 = 6.106, P < 0.05). However, translocation by Enterobacteriaceae, the organisms commonly responsible for spontaneous bacteremia and peritonitis in cirrhosis, was only observed in 25% of the cases. The prevalence of bacterial translocation in the 22 cirrhotic patients undergoing selective intestinal decontamination, all Child-Pugh class B and C, was 4.5%. The Child-Pugh score was the only independent predictive factor for bacterial translocation (odds ratio 2.22, P = 0.02). CONCLUSIONS: Translocation of enteric organisms to mesenteric lymph nodes is increased in patients with advanced cirrhosis and is reduced to the level found in non-cirrhotic patients by selective intestinal decontamination. PMID- 11211905 TI - Overexpression of endothelin-1 in bile duct ligated rats: correlation with activation of hepatic stellate cells and portal pressure. AB - BACKGROUND/AIMS: Hepatic stellate cells (HSC) are involved in the pathogenesis of liver fibrosis; although ET-1 is increased in cirrhosis, its pathophysiological role in fibrogenesis and portal hypertension remains controversial. The aim of this study was to investigate splanchnic hemodynamics and to correlate them with changes in ET-1 expression and HSC activation in bile duct ligated (BDL) rats. METHODS/RESULTS: Expression of the ET-1 gene was increased early as measured by quantitative reverse transcriptase-polymerase chain reaction (6-fold 3 days after BDL) whereas ET-1 peptide measured by RIA increased significantly only in the late phase (30-fold at 28 days). There was a linear correlation between portal pressure and the amount of ET-1 in the portal vein (r = 0.66; P = 0.003), as well as between ET-1 and the volume fraction of myofibroblasts (r = 0.80, P < 10(-7)) as assessed by morphometry and immunohistochemical staining using alpha-smooth muscle actin. CONCLUSIONS: During chronic liver injury activation of HSCs and of preproET-1 mRNA is accentuated in the early phase after BDL. The late increase in ET-1 peptide may indicate that this peptide is only secondarily involved in HSC activation. The correlation between ET-1 in portal vein and portal pressure suggests that ET-1 may play an important role in the development of portal hypertension. PMID- 11211906 TI - Visualization of the transport of primary and secondary bile acids across liver tissue in rats: in vivo study with fluorescent bile acids. AB - BACKGROUND/AIMS: Lysyl fluorescein conjugated bile acid analogues (LFCBAA) closely parallel their natural counterparts. To assess LFCBAA as a tool for the visualization of bile acid transport within liver tissue. METHODS: Wistar rats were administered physiological concentrations of the primary bile acid analogue cholyllysyl fluoroscein (CLF) and of the secondary bile acid analogue lithocholyllysyl fluorescein (LLF) and serial liver biopsies were taken at fixed intervals. Both compounds were also injected retrogradely into the biliary tree. Frozen sections were examined by fluorescence microscopy. RESULTS: Both CLF and LLF were rapidly taken up from sinusoidal blood but differed significantly in their hepatic handling. CLF was rapidly transported into bile, whereas LLF transport was slower and produced significantly more bile duct fluorescence. LLF clearance showed a lobular gradient with last remaining bile acid being confined largely to zone 3. Both compounds were avidly taken up by cholangiocytes after injection intravenously or retrogradely into the biliary tree. CONCLUSIONS: Visualization of LFCBAA by fluorescence microscopy may yield further information regarding hepatobiliary bile acid localization during studies of physiological and pathological mechanisms involved in transport of bile acids. The presence of both compounds within cholangiocytes strongly suggests that they may undergo a degree of chole-hepatic recirculation. PMID- 11211907 TI - A prognostic model for predicting survival in cirrhosis with ascites. AB - BACKGROUND/AIMS: Parameters evaluating renal function and systemic hemodynamics are of prognostic significance in cirrhosis with ascites but are rarely used in the evaluation of survival of these patients. The aim of the current study was to develop a prognostic model to estimate survival of patients with cirrhosis and ascites. METHODS: 216 Cirrhotic patients admitted to hospital for the treatment of ascites were evaluated. Thirty-two demographic, clinical and laboratory variables, including parameters assessing liver and renal function and systemic hemodynamics, were analyzed as predictive factors of survival by using a Cox regression model. RESULTS: Four variables had independent prognostic value: renal water excretion, as assessed by measuring diuresis after water load, mean arterial pressure, Child-Pugh class, and serum creatinine. According to these features a prognostic index was calculated that allows to estimate survival in patients with cirrhosis and ascites. The model accurately predicted survival in an independent series of 84 patients with cirrhosis and ascites. CONCLUSION: A prognostic model that uses four easily available variables and predicts prognosis in cirrhotic patients with ascites has been developed. This model may be useful in the evaluation of patients with ascites for liver transplantation. PMID- 11211908 TI - Dynamics of albumin in plasma and ascitic fluid in patients with cirrhosis. AB - BACKGROUND/AIMS: To determine dynamics of albumin in plasma and ascitic fluid of patients with cirrhosis. METHODS: Forty-seven patients were classified in four groups: I--patients without fluid retention; II--patients with ascites not resistant to subsequent diuretic treatment; III--recompensated patients during diuretic treatment; and IV--patients with diuretic-resistant ascites. Transvascular and transperitoneal albumin transports were quantified by 131I /125I-labelled human albumin. RESULTS: TER(P) (i.e. the fraction of intravascular albumin (IVM) passing from plasma into the interstitial space per hour) was increased in all groups. In group IV patients the transport rate of albumin from plasma into the ascitic fluid (TER(PA)) was significantly higher than the transport rate from the ascitic fluid back into the plasma: TER(AP) (0.45 vs. 0.26% IVM/h, P < 0.002). In group II patients TER(PA) was similar to TER(AP) (0.27 vs. 0.25% IVM/h, ns). A direct correlation was found between TER(PA) and TER(AP) in both groups of patients (r = 0.78, P < 0.001). CONCLUSION: In non resistant ascites, there is a steady state between the transport of albumin into the peritoneal cavity and back into the plasma, but in resistant ascites the former transport is elevated. Thus, local factors may be important to treatment of ascites. PMID- 11211909 TI - Induction of cytokine production and proliferation of memory lymphocytes by murine liver dendritic cell progenitors: role of these progenitors as immunogenic resident antigen-presenting cells in the liver. AB - BACKGROUND/AIMS: Many pathogenic organisms, including hepatotrophic viruses enter the liver and induce an immune response, but there is little information about the immunogenic resident antigen-presenting cells. The aim of this study was to determine whether dendritic cells in the liver are immunogenic antigen-presenting cells. METHODS: Liver dendritic cell progenitors were enriched from normal C57BL/6 mice by culturing non-parenchymal cells with granulocyte-macrophage colony stimulating factor for 7 days. Then the surface antigen (MHC class II, CD86) expression, endocytic capacity, ability to induce cytokines, and the proliferation of memory lymphocytes were investigated. RESULTS: Freshly enriched liver dendritic cell progenitors exhibited an immature phenotype and failed to stimulate allogenic T cells. However, the progenitors underwent maturation following exposure to antigens such as hepatitis B surface antigen and keyhole limpet hemocyanin. The progenitors then became strong stimulators of allogenic T cells, supported the production of interleukin-12 and interferon-gamma, and induced the proliferation of antigen-specific memory lymphocytes. CONCLUSIONS: Dendritic cell progenitors are immunogenic resident antigen-presenting cells in the liver. Simultaneous investigation of both tolerogenic and immunogenic resident antigen-presenting cells may provide insights into the pathogenesis of persistent infection and autoimmmune diseases of the liver. PMID- 11211910 TI - Human hepatocyte cell lines proliferating as cohesive spheroid colonies in alginate markedly upregulate both synthetic and detoxificatory liver function. AB - BACKGROUND/AIMS: Bio-artificial liver support systems for treatment of hepatic failure require maintained expression of hepatocyte function in vitro. We studied cultures of human hepatocyte cell-lines proliferating within alginate beads, investigating the hypothesis that 3-dimensional cohesive colonies of hepatocyte cell-lines would achieve polarity and cell-to-cell contact resulting in upregulation of function. METHODS: HepG2 and HHY41 human cell lines in alginate beads were cultured for >20 days. RESULTS: Proliferation was maintained for 20 days. Production of albumin, prothrombin, fibrinogen, alpha-1-acid glycoprotein and alpha-1-antitrypsin was maintained throughout, maximal at days 8-10, when upregulation was 300-1100% compared with monolayer cultures at similar cell number per unit volume. Detoxificatory functions: ethoxyresorufin deethylase activity, androstenedione metabolism, and urea synthesis from arginine was also increased several-fold. Function returned to pre-freezing levels within 18 h of thawing after cryopreservation of cells in alginate. Electron microscopy revealed spherical colonies of cells of cuboidal shape, with cell-to-cell contact via desmosomes and junctional complexes, abundant microvilli, and cytoplasmic appearances suggesting transcriptionally active hepatocytes. CONCLUSION: Hepatocyte cell-lines, proliferating in alginate express a range of liver specific functions at levels approaching those found in vivo, relevant to their use in liver support systems. PMID- 11211911 TI - Expression of hepatocyte growth factor in human hepatocellular carcinoma. AB - BACKGROUND/AIMS: We have shown that hepatocyte growth factor, secreted by human liver myofibroblasts, promoted in vitro invasion of human hepatocellular carcinoma cell lines. The aim of this work was to measure hepatocyte growth factor expression in 29 human hepatocellular carcinomas and the corresponding peri-tumoral livers. METHODS: We used reverse transcription-polymerase chain reaction, in situ hybridization, ELISA and Western blot. RESULTS: Sixty-two of tested hepatocellular carcinomas were positive by reverse transcription polymerase chain reaction. With in situ hybridization, a signal was found in every sample. In many cases, the signal was localized in cells labeled with an anti-smooth muscle alpka-actin antibody, while hepatocytes were mostly non labeled. ELISA, performed in 15 pairs of hepatocellular carcinomas and surrounding livers, detected hepatocyte growth factor in every sample with wide variations. Hepatocellular carcinomas that had developed in non-cirrhotic livers contained essentially the same amount of hepatocyte growth factor as the matching non-tumoral liver. In cirrhotic livers, the hepatocyte growth factor content of the tumors was significantly lower than that of the surrounding cirrhotic livers. CONCLUSIONS: These data indicate that hepatocyte growth factor is expressed at significant levels in every hepatocellular carcinoma tested and that its expression takes place in the stromal myofibroblasts. PMID- 11211912 TI - Increased cancer risk after liver transplantation: a population-based study. AB - BACKGROUND/AIMS: Development of de novo malignancies emerges as a serious long term complication after liver transplantation. METHODS: We reviewed the medical records of 174 adult one-year survivors for de novo malignancies. The observed cancer rates were compared with the expected cancer rates in the Dutch population. RESULTS: Twenty-one of the 174 patients developed 23 malignancies (12%). Skin and lip cancer accounted for 12 of the 23 malignancies (52%). Only one patient had a B-cell lymphoma. The cumulative risk for de novo malignancy was 6, 20, and 55% at 5, 10, and 15 years after transplantation, respectively. The overall relative risk (RR) as compared with the general population was 4.3 (95% confidence interval 2.4-7.1). Significantly increased RRs were observed for non melanoma skin cancer (RR 70.0), non-skin solid cancer (RR 2.7), renal cell cancer (RR 30.0), and colon cancer (RR 12.5). Multivariate analysis showed that an age > 40 years and pretransplant use of immunosuppression were significant risk factors. CONCLUSIONS: An increased risk of cancer exists after liver transplantation, for both for skin/lip cancer, and other solid tumors. Older age and the use of immunosuppression are risk factors. PMID- 11211914 TI - Animal models of bronchial asthma. AB - Due to the continuous increase in prevalence and morbidity in asthma, there is an urgent need to improve present therapy by drugs with new modes of actions. In contrast to many human diseases, allergic asthma does not occur in the animal world. Therefore, we have to mimic some characteristic feature of asthma in animals. For this reason, a wide variety of animal models have been developed and are employed in the search for new chemical entities for asthma therapy. In the present paper, the experimental models of the most characteristic asthma symptoms are critically reviewed. PMID- 11211913 TI - Cost-benefit analysis of a nationwide infant immunization programme against hepatitis A in an area of intermediate endemicity. AB - BACKGROUND/AIMS: The availability of safe and effective Hepatitis A vaccines prompts an evaluation of a nationwide infant vaccination campaign to supplement strategies aimed at high-risk groups such as travellers and military personnel. METHODS: A spreadsheet model was used to estimate costs and benefits of a nationwide infant immunization programme against Hepatitis A for the period from 1997-2014 in Israel. RESULTS: Immunizing all one year olds in Israel from 1997 2014 would for a cost of $32.0 million to the health services and $42.1 million to society (including $10.1 million lost work and transport costs), reduce the number of cases of Hepatitis A during the next 45 years from 181,000 to 47,000. This would save $57.5 million in health service resources alone, $32.0 million in averted work absences and transport costs in addition to a further $17.0 million in averted premature mortality costs. The health service, resource and societal benefit:cost ratios are 1.80:1, 2.13:1 and 2.54:1, respectively. CONCLUSIONS: The recent adoption of a nationwide infant HAV immunisation policy in Israel is both medically and economically justifiable. PMID- 11211915 TI - Dexamethasone enhances P-selectin mRNA expression in hyperoxic rat lungs. AB - OBJECTIVE AND DESIGN: To test the hypothesis that glucocorticoid administration would diminish the lung expression of P-selectin mRNA in hyperoxia-exposed rats. ANIMALS: Adult male Sprague-Dawley rats were divided into 6 separate groups containing 10 to 13 animals per group. TREATMENT: Rats were dosed with 1 mg/kg of dexamethasone or vehicle only, ip. Immediately after dosing, animals were placed in > 95 % oxygen. Some animals were maintained in room air and are presented as 0 h of exposure to hyperoxia. Another group of animals was dosed with 10 mg/kg lipopolysaccharide (LPS) ip immediately after dosing with either dexamethasone or vehicle as above. METHODS: At 24 or 48 h, lung samples were obtained, and lung weight to body weight ratios calculated. In the LPS studies, samples were obtained 4 h after LPS dosing. In a subset of animals, lung sections were hybridized for P-selectin mRNA. All data except for hybridizations were analyzed with three-way ANOVA, with subsequent post-hoc testing. P-selectin hybridizations were quantified by counting the number of positive vessels per high-powered field, and subsequently analyzed by unpaired Student's t-test. Immunohistochemical analyses for P-selectin expression were also performed to determine whether changes in P-selectin mRNA were associated with differences in protein expression. All data are expressed as means +/- SEM. RESULTS: Rats dosed with dexamethasone had higher lung/body weight ratios after 24 and 48 h of exposure to hyperoxia than did similarly exposed rats dosed only with vehicle (at 48 h, 0.87 +/- 0.04 versus 0.65 +/- 0.06, respectively, P < 0.05). The higher ratios in hyperoxic animals dosed with dexamethasone were associated with much higher levels of lung expression for P-selectin mRNA than was observed in similarly exposed rats dosed with vehicle alone (at 48 h, 3.93 +/- 1.02, versus 0.20 +/- 0.06, respectively, P < 0.01). In contrast dexamethasone dosing lead to lower lung P-selectin mRNA expression in animals exposed to LPS (1.23 +/- 1.08 in dexamethasone dosed animals versus 6.80 +/- 0.92 in vehicle only dosed animals). Consistent with the mRNA data, P-selectin immunoreactivity increased as a function of hyperoxia-exposure time in animals dosed with dexamethasone, while immunoreactivity decreased as a function of hyperoxia-exposure time in animals dosed with vehicle only. CONCLUSIONS: Increased P-selectin mRNA combined with increased P-selectin protein expression in animals exposed to hyperoxia and dosed with dexamethasone suggests that enhanced expression of P-selectin may contribute to the greater lung injury and inflammation caused by hyperoxia in rats treated with dexamethasone. PMID- 11211916 TI - Studies on the effects of adenosine A3 receptor stimulation on human eosinophils isolated from non-asthmatic or asthmatic donors. AB - OBJECTIVE: This study was designed to demonstrate the presence of adenosine A3 receptors on human peripheral blood eosinophils, and to investigate the effect of A3 receptor stimulation on eosinophil function. MATERIAL: Eosinophils from either non-asthmatic or asthmatic donors. METHODS: Eosinophils were isolated from peripheral venous blood by discontinuous gradient centrifugation and negative immunoselection. Receptor localisation was investigated by immunoblotting and by immunocytochemistry using a novel antibody specific for the human A3 receptor. Two pharmacological responses were studied: elevation of intracellular calcium in single eosinophils, measured by microfluorimetry, and hydrogen peroxide generation in cell suspensions. RESULTS: The expression of A3 receptors by eosinophils was confirmed using the selective antibody. Addition of the A3 receptor selective agonist, IB-MECA (100 nM), produced increases in intracellular calcium in less than 10% of the eosinophils isolated from non-asthmatic donors. These responses were only partially attenuated with the A3 receptor antagonist, I ABOPX. IB-MECA (0.001-1000 nM) did not stimulate hydrogen peroxide (H2O2) generation, nor did it enhance fMLP- or C5a-stimulated generation of H2O2. In fact high concentrations of IB-MECA inhibited the generation of H2O2 (when stimulated by fMLP or C5a), an effect probably mediated by A2 receptors. Similar results were obtained using eosinophils from asthmatic donors. CONCLUSIONS: Stimulation of adenosine A3 receptors does not appear to be a prime mechanism for free radical generation by human peripheral blood eosinophils. PMID- 11211917 TI - Neutrophil infiltration as a crucial step for monocyte chemoattractant protein (MCP)-1 to attract monocytes in lipopolysaccharide-induced arthritis in rabbits. AB - OBJECTIVE AND DESIGN: To evaluate the mechanism whereby monocyte chemoattractant protein (MCP)-1 attracts monocytes in vivo. SUBJECTS: New Zealand white rabbits (175 rabbits) were used. TREATMENT: LPS, MCP-1 or IL-8 was injected into knee joints. Antibodies against various cytokines or IL-1 receptor antagonist were injected to neutralize cytokine activities. METHODS: The numbers of leukocyte populations, levels of cytokines in joints were estimated. RESULTS: Partial inhibition of neutrophil influx with anti-IL-8 IgG (10 microg) suppressed LPS induced macrophage influx by 43 +/- 8.5% (p<0.05) without affecting the MCP-1 level. Intraarticular injection of MCP-1 (1-30 microg) induced macrophage influx. The event was accompanied by a small number of neutrophils in an early phase. Co injection of IL-8 (1.0 microg) enhanced the MCP-1-induced macrophage infiltration (p < 0.01). In neutrophil-depleted rabbits, LPS failed to induce macrophage influx even though the MCP-1 level was maintained, and macrophage influx following exogenously administered MCP-1 was also dramatically inhibited. CONCLUSIONS: Early events associated with neutrophil infiltration appear to be important for MCP-1 to induce a later macrophage influx in LPS-arthritis. PMID- 11211918 TI - Retinoic acid enhances the effect of collagen on bone union, following induced non-union defect in guinea pig ulna. AB - OBJECTIVE AND DESIGN: The aim of the present study is to evaluate the involvement of retinoic acid and collagen in wound healing, by combining them in a therapeutic modality for treating a non-union bone defect in a guinea-pig ulnar bone model. METHODS: a 4-mm disc was excised from the guinea-pig's ulnar-bone, and the space formed between the two ulnar fragments was filled with either collagen solution, retinoic acid solution or a combination of both. The guinea pigs were sacrificed 2 or 6 weeks later, and the defected ulnar bones were studied by X-ray, by histology and by computerized histomorphometry. RESULTS: After 6 weeks, the long bone area fraction within the histological sections of the bone, was increased after treatment with this mixture by 180%, as compared to the untreated controls. The cartilage area in those sections was decreased by 44% after the combined treatment, as compared to increases of 133% and 182% following treatments with collagen alone. CONCLUSION: These findings demonstrate that addition of 500 IU of retinoic acid to collagen at a site of a bone defect, is superior to either agent in enhancing regeneration of new bone, achieving union across the defect and leading to its complete repair. PMID- 11211919 TI - FMLP-induced formation of F-actin in HL60 cells is dependent on PI3-K but not on intracellular Ca2+, PKC, ERK or p38 MAPK. AB - OBJECTIVE AND DESIGN: To further understand the mechanisms of signal transduction pathways for the formation of F-actin (polymerization of actin) and the activation of NADPH oxidase in phagocytic cells, the effects of various inhibitors on them were studied. MATERIALS AND METHODS: Differentiated HL60 cells were studied to examine their N-formyl-methionyl-leucyl-phenylalanine (fMLP) stimulated formation of F-actin and activation of NADPH oxidase following treatment with various inhibitors. These included a protein kinase C (PKC) inhibitor (GF 109203X), a phosphatidylinositide 3 kinase (PI3-K) inhibitor (wortmannin), an extracellular response kinase (ERK) inhibitor (PD 98059), a p38 mitogen-activated protein kinase (MAPK) inhibitor (SB 203580) and an intracellular Ca2+ -chelator (BAPTA-AM). RESULTS: The treatment with wortmannin suppressed the formation of F-actin, with less suppression of the activation of NADPH oxidase. BAPTA-AM and GF 109203X did not attenuate the formation of F-actin but completely inhibited the activation of NADPH oxidase. PD 98059 and SB 203580 partially inhibited the activation of NADPH oxidase without influence on the formation of F-actin. Furthermore, wortmannin but not BAPTA-AM and GF 109203X inhibited the fMLP-induced activation of Akt, which is known to regulate NADPH oxidase. CONCLUSIONS: These results suggest that the formation of F-actin is dependent on PI3-K and independent of PKC, ERK and p38 MAPK as well as the increase in intracellular Ca2+, whereas the activation of NADPH oxidase is partly dependent on ERK, p38 MAPK, Akt regulated by PI3-K, and strongly dependent on the activation of PKC and the increase in intracellular Ca2+. PMID- 11211920 TI - The in vitro and in vivo pharmacology of antisense oligonucleotides targeted to murine Stat6. AB - OBJECTIVE AND DESIGN: This study was designed to establish whether phosphorothioate (PS) antisense oligonucleotides (AS-ODN) targeted to Stat6 were active in vivo in a mouse model of active sensitisation. MATERIALS: Female Balb/c mice (6-8) per group were used for in vivo study. TREATMENT: Mice were treated with active PS AS-ODNs determined in initial in vitro studies. Compounds were dosed daily (3-30mg/kg i.v.) over the course of sensitisation to ovalbumin. METHODS: Stat6 mRNA and protein levels were determined in the spleen after treatment (quantitative northern and western analysis respectively), in addition to serum IgE (ELISA). ANOVA was used to determine any significant differences between groups. RESULTS: Both of the AS-ODNs tested in vivo, down regulated Stat6 mRNA and protein levels in the spleen by 40-50% although there was no effect on serum IgE. These treatments also induced splenomegaly in vivo and caused splenocyte proliferation in vitro. CONCLUSIONS: The AS-ODNs used can down regulate Stat6 mRNA and protein although not sufficiently to influence IgE levels. These effects are likely to be complicated in vivo by the immune stimulation evident as splenomegaly. PMID- 11211921 TI - Reactive oxygen intermediates and eicosanoid production by kupffer cells and infiltrated macrophages in acute and chronic liver injury induced in rats by CCl4. AB - OBJECTIVE AND DESIGN: The aim of the present study was to characterize during acute and chronic liver injury induced by CCl4, macrophage phenotypes and whether a change in reactive oxygen intermediates (ROI) and eicosanoids production by Kupffer cells (KC) was observed. MATERIAL AND METHODS: Liver steato-necrosis and cirrhosis were induced in rats after 3 weeks and 9 weeks of CCl4 intoxication, respectively. Monocytes and tissue macrophages were identified by immunohistochemical study using monoclonal antibodies ED-1 and tissue macrophages using the antibody ED-2. The release of ROI and eicosanoids in response to the phorbol ester TPA (protein kinase activator) and to the calcium ionophore A23187 was assessed in cultivated cells. RESULTS: As compared to healthy controls, livers of rats with steato-necrosis or cirrhosis exhibited a significant increase of ED-1 and ED-2 positive cells. Only KC from rats with liver steato-necrosis were found to have higher A23187, TPA + A23187 or opsonized zymosan induced ROI production than healthy controls (p < 0.01). After TPA + A23187 or opsonized zymosan stimulation, KC from both rats with steato-necrosis or cirrhosis produced more TxB2 and leukotrienes and less PGE2 as compared to healthy controls (p <0.05). CONCLUSIONS: These results suggest an influx of monocytes into the liver during acute and chronic injury induced by CCl4. Functional changes of this inflammatory infiltrate have been demonstrated with an increase of ROI production only in the early stage of liver injury whereas a rise in KC leukotriene production and an imbalance between cytoprotective and cytotoxic prostanoids were observed at all stages of liver disease. PMID- 11211922 TI - Mechanism underlying acute resident leukocyte disappearance induced by immunological and non-immunological stimuli in rats: evidence for a role for the coagulation system. AB - OBJECTIVE: To investigate the involvement of the fibrinogen-fibrin system in the acute reduction of the resident leukocyte population following pleural inflammation. METHODS: Sensitized and naive rats were injected intrapleurally (i.pl.) with antigen (ovalbumin) and platelet-activating factor (PAF) or bradykinin, respectively. Heparin (0.25 U/cavity), EDTA (80 microg/cavity) and hirudin (1 U/cavity) were injected locally 5 min before challenge, whereas fucoidin was injected intraperitoneally 30 min before stimulation. RESULTS: Antigen challenge led to a rapid reduction in the number of resident leukocytes 30 min post-challenge (from 7.7 +/- 0.4 x 10(6) cells/cavity to 2.3 +/- 0.2 x 106 cells/cavity, n = 6, p < 0.001). The pleural stimulation of naive rats with either PAF or bradykinin also led to a significant decrease in the pleural leukocyte population, which occurred in parallel with the formation of a fibrin meshwork containing captured cells, as attested by electron microscopy. Heparin prevented the drop in the total leukocyte numbers, without modifying either plasma leakage or histamine release at 30 min or the subsequent neutrophil and eosinophil infiltration noted 4 and 24 h post-challenge, respectively. Similarly, hirudin and EDTA prevented the antigen-induced leukocyte disappearance reaction. Heparin also impaired the drop in the pleural leukocyte numbers evoked by PAF and bradykinin. CONCLUSION: Our data show that the pleural resident cell disappearance phenomenon noted early after inflammatory provocation depends on the activation of the fibrinogen-fibrin system, and is not required for the subsequent leukocyte recruitment. PMID- 11211923 TI - Oral beta-stimulants can inhibit passive cutaneous anaphylaxis in rats through an indirect inhibitory mechanism: possible involvement of afferent and efferent nervous system via gastric beta2-adrenoceptor stimulation. AB - OBJECTIVE AND DESIGN: We previously demonstrated that oral l-ephedrine exerts an extremely rapid (within 20 s) inhibition of 48-h passive cutaneous anaphylaxis reaction (PCA) in rats by a possibly unidentified mode of action. In the present experiments, we elucidated the mechanism of the PCA inhibition by l-ephedrine using adrenoceptor agonists and antagonists. MATERIALS: Rat antiserum was prepared with dinitrophenylated Ascaris suum extract + Bordetella pertussis. TREATMENT: Passively skin-sensitised Wistar rats were mainly used. l-Ephedrine, and adrenoceptor agonists and antagonists were orally administered immediately before PCA provocation. Catecholamine depleting (6-hydroxydopamine, 6-OHDA), amine depleting (reserpine) or ganglion blocking (hexamethonium) agent was intraperitoneally or intravenously administered before the provocation. METHODS: The effects of the drugs on PCA were assessed by inhibition of the dye leakage. RESULTS: beta-(propranolol) and beta2-(butoxamine) blocking agents reduced the inhibition of PCA by l-ephedrine, while the inhibition was not altered by either an a-blocking agent (phentolamine) or a beta1-(atenolol) selective antagonist. On the other hand, beta-(isoproterenol) and beta2-selective (salbutamol) agonists showed extremely rapid inhibition of PCA. However, the beta-selective agonist (dobutamine) had no effect on the reaction. The pretreatment with hexamethonium, reserpine or 6-OH-DA substantially attenuated the inhibitory effect of l ephedrine on PCA. CONCLUSIONS: The results strongly suggest that beta2 adrenoceptors locate in the stomach and that their receptor excitement finally may lead to the inhibition of PCA via the stimulation of the central and peripheral nervous systems. PMID- 11211924 TI - L-arginine modifies free radical production and the development of experimental allergic encephalomyelitis. AB - OBJECTIVES AND DESIGN: The present investigation examines the effects of increasing central nervous system (CNS) levels of nitric oxide (NO), via the administration of L-arginine, on the development of experimental allergic encephalomyelitis (EAE). SUBJECTS: EAE was induced in male Lewis rats (200-250 g). TREATMENT: Normal rats were orally dosed with L-arginine (300 mg/kg body weight) once daily for 12 days. EAE-sensitised animals received L-arginine (300 mg/kg body weight) once daily from day 1 to 12 post-inoculation. METHODS: Neurological and histological development of EAE were assessed. In addition, CNS cytosol levels of nitrite, superoxide and hydrogen peroxide were measured. Results were analysed using the Mann Whitney U-test and Chi-squared test. RESULTS: L-arginine administration significantly delayed disease onset (p < 0.05) and reduced the severity of neurological (p < 0.05) and histological (p < 0.001) signs of EAE. Treatment with L-arginine caused a significant elevation in CNS nitrite concentrations (p < 0.05) which in EAE-sensitised animals was associated with a concomitant and dramatic decrease in superoxide (p < 0.05) and hydrogen peroxide (p < 0.05) levels. CONCLUSIONS: The results suggest that NO may act as a protective molecule during the development of EAE possibly via the modulation of oxidant-mediated neuroinflammation. PMID- 11211926 TI - Neutrophil migration and aggregation induced by euphorbin, a lectin from the latex of Euphorbia milii, var. milii. AB - OBJECTIVE AND DESIGN: To study the neutrophil migration and aggregation induced by euphorbin, a D-galactose binding lectin from Euphorbia milii var. milli latex. MATERIALS AND METHODS: Euphorbin-induced neutrophil migration was evaluated in vivo and in vitro, in the absence or presence of soluble D-galactose. Neutrophil aggregation induced in vitro by euphorbin was determined by light microscopy. RESULTS: The neutrophil migration inducing activity of euphorbin was dose dependent and inhibited by soluble D-galactose. Neutrophil aggregation was rapidly reversed when provoked by 0.1 mg/ml euphorbin. In higher concentrations, euphorbin caused persistent and more extensive neutrophil aggregation. CONCLUSIONS: Euphorbin induced neutrophil migration through its sugar recognition property. The transitory neutrophil aggregation, induced by a euphorbin quantity similar to that able to cause maximal chemotactic response, is characteristic of homotypic neutrophil adhesion, whereas persistent aggregation, provoked by higher euphorbin quantities, corresponds to cell agglutination by a multivalent lectin. PMID- 11211925 TI - Urethane suppresses rat lung inducible cyclooxygenase and nitric oxide synthase mRNA levels. AB - OBJECTIVE AND DESIGN: The purpose of the present study was to evaluate the effect of urethane, pentobarbital sodium and ketamine-xylazine anesthesia upon constitutive and inducible cyclooxygenase (COX-1; COX-2) and nitric oxide synthase (eNOS; iNOS) mRNA levels in the lung. METHODS: mRNA levels were determined by the semiquantitative RT-PCR technique. TREATMENT: Urethane (1.1 g/kg ip), Pentobarbital Sodium (40 mg/kg ip), and ketamine (85 mg/kg) - xylazine (15 mg/kg, im). Non-anesthetized animals served as controls. MATERIAL: Sprague Dawley rat lungs RESULTS: Urethane significantly decreased COX-1 and COX-2 mRNA levels to 30% of control values. This agent had no effect upon eNOS, but completely suppressed iNOS mRNA levels. Pentobarbital sodium and ketamine had no effect on the mRNA levels for COX-1 and COX-2 the lung. CONCLUSIONS: Urethane has a suppressive effect on COX and iNOS RNA message in the lung and for this reason it should be avoided as an anesthetic when lung inflammatory processes are experimentally evaluated in the rat. PMID- 11211927 TI - Assay of cyclooxygenase-1 and 2 in human monocytes. AB - OBJECTIVE AND DESIGN: There is frequently poor correlation between in vitro methods for calculated cyclooxygenase (COX)-1/COX-2 selectivities of inflammatory agents. Therefore, we have examined the use of a single stimulus in a single cell type containing both COX isoforms, for determining the selectivities of COX inhibitory agents. METHODS: Fresh human monocytes were stimulated with arachidonic acid (AA; 10 microM) for 15 min and prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) production were used as a measure of COX-1 activity. To measure COX-2 activity, cells were transiently pre-treated with aspirin to irreversibly inhibit constitutive COX-1, treated with lipopolysaccharide (LPS) to induce COX-2 and then stimulated with AA. RESULTS: Eicosanoid production in resting monocytes was predominantly COX-1 derived since it was not inhibited by NS-398 and also, COX-2 was not detectable. In LPS treated monocytes pre-treated transiently with aspirin, neither the level of induced COX-2 nor the activity was affected. Using the mean of the results for PGE2 and TXB2 inhibition, the COX 1/COX-2 ratios of the IC50 values for aspirin and NS-398 are < 0.1 and > 130, respectively. CONCLUSIONS: This study has provided a system for investigating inhibition of COX isotypes without the potentially confounding effects of using different cell types with different stimuli for each isotype as seen in other published systems. Dose responses to aspirin and NS-398 which are COX- and COX-2 selective inhibitors respectively, confirmed the utility of this system. PMID- 11211928 TI - Characterization of chenodeoxycholic acid as an endogenous antagonist of the G coupled formyl peptide receptors. AB - OBJECTIVE AND DESIGN: To demonstrate the role of bile acids in immune modulation we examined the ability of select bile acids to inhibit leukocyte migration and chemoattractant receptor function. MATERIALS: To elucidate this mechanism, we employed primary human monocytes, neutrophils and cell lines transfected to express either the high affinity fMLP receptor (FPR) or the low affinity fMLP receptor like 1 (FPRL1). TREATMENT: Cells were treated with chenodeoxycholic acid (CDCA) and related bile acids in a 0-400 micromolar range. METHOD: Cell viability, chemotaxis and calcium flux analysis were preformed. RESULTS: We observed that pathophysiological levels (< or = 150 micromolar) of CDCA competitively inhibited 3H-fMLP binding to human monocytes, FPR and FPRL1 transfected cells. Additionally, CDCA reduced both the chemotactic and calcium flux responses induced by fMLP or "W" peptide. Further, CDCA inhibited anti-FPR antibody binding to monocytes. CONCLUSIONS: CDCA selectively inhibited human leukocyte chemotaxis and calcium flux induced by fMLP, but not other chemoattractants, suggesting a mechanism for inhibition of inflammation and suppression of innate immune response. PMID- 11211929 TI - Killing tumour cells by alkylphosphocholines: evidence for involvement of CD95. AB - Many lipids act as cellular messengers and lead to a variety of different cellular responses. Out of the group of these compounds the ceramides are able to induce apoptosis, and some synthetic lipids can mimic this effect. Apoptosis is an important mechanism whereby chemotherapeutics exhibit their anti-oncogenic activity. Although, some lipid analogues were used in clinical trials, they exert severe side effects and their mechanism of action is widely unknown. We present here a new class of synthetic alkylphosphocholines (APC) that induce programmed cell death in leukaemia cells. The signs of apoptosis arise after 1 h of incubation with these compounds as shown by phosphatidylserine externalisation followed by caspase activation and DNA fragmentation. We demonstrate that the molecular target of these lipids is upstream of caspases and Bcl-2. Experiments with FADD dominant negative cells reveal that induction of apoptosis occurs on the level of CD95 and that these compounds can now be optimised for their capacity to activate the apoptosis-inducing receptor CD95. PMID- 11211931 TI - The effects of chelidonine on tubulin polymerisation, cell cycle progression and selected signal transmission pathways. AB - Chelidonine is a tertiary benzophenanthridine alkaloid known to cause mitotic arrest and to interact weakly with tubulin. Our interest in chelidonine began when we found it to be a major contaminant of Ukrain, which is a compound reported to be selectively toxic to malignant cells. The effects of chelidonine in two normal (monkey kidney and Hs27), two transformed (Vero and Graham 293) and two malignant (WHCO5 and HeLa) cell lines, were examined. Chelidonine proved to be a weak inhibitor of cell growth, but no evidence for selective cytotoxicity was found in this study. It was confirmed that chelidonine inhibits tubulin polymerisation (IC50 = 24 microM), explaining its ability to disrupt microtubular structure in cells. A G2/M arrest results, which is characterised by abnormal metaphase morphology, increased levels of cyclin B1 and enhanced cdc2 kinase activity. Exposure of all cell lines examined to chelidonine leads to activation of the stress-activated protein kinase/jun kinase pathway (SAPK/JNK). PMID- 11211930 TI - Heteromeric connexons formed by the lens connexins, connexin43 and connexin56. AB - In the eye lens, three connexins have been detected in epithelial cells and bow region/differentiating fiber cells, suggesting the possible formation of heteromeric gap junction channels. To study possible interactions between Cx56 and Cx43, we stably transfected a normal rat kidney cell line (NRK) that expresses Cx43 with Cx56 (NRK-Cx56). Similar to the lens, several bands of Cx56 corresponding to phosphorylated forms were detected by immunoblotting in NRK-Cx56 cells. Immunofluorescence studies showed co-localization of Cx56 with Cx43 in the perinuclear region and at appositional membranes. Connexin hexamers in NRK-Cx56 cells contained both Cx43 and Cx56 as demonstrated by sedimentation through sucrose gradients. Immunoprecipitation of Cx56 from sucrose gradient fractions resulted in co-precipitation of Cx43 from NRK-Cx56 cells suggesting the presence of relatively stable interactions between the two connexins. Double whole-cell patch-clamp experiments showed that the voltage-dependence of Gmin in NRK-Cx56 cells differed from that in NRK cells. Moreover, stable interactions between Cx43 and Cx56 were also demonstrated in the embryonic chicken lens by co-precipitation of Cx43 in Cx56 immunoprecipitates. These data suggest that Cx43 and Cx56 form heteromeric connexons in NRK-Cx56 cells as well as in the lens in vivo leading to differences in channel properties which might contribute to the variations in gap junctional intercellular communication observed in different regions of the lens. PMID- 11211932 TI - Supramolecular dynamics of gap junctions. AB - During the life cycle of a membrane protein its molecular structure may change and for aggregated proteins this process may be observed on the supramolecular level. Here we demonstrate that this is the case for gap junction channels which maintain cell-cell communication. Freshly synthesized connexins are integrated as hexamers (connexons) into the plasma membrane where they form plaques after pairing with connexons of an attached cell. We inhibited protein trafficking by applying the fungal metabolite brefeldin A (BFA), quantified cell-cell coupling by calcein transfer and fluorescence-activated flow cytometry, and examined the degradation and formation of gap junction plaques by indirect immunofluorescence and immunogold labeling. Under control conditions 50% of the detected plaques were ubiquitylated and less than 10% showed a two-dimensional crystalline packing. One hour after BFA reversal about 60% of the plaques were crystalline and ubiquitylation dropped to 14%. Label for ubiquitin was predominantly found on non-crystalline plaques. We, therefore, conclude that newly formed gap junction plaques are of crystalline morphology which changes to a pleomorphic structure when individual channels are modified during their aging process. This dynamic in plaque morphology correlates with channel inactivation and plaque ubiquitylation. PMID- 11211933 TI - Mycobacterial surface moieties are released from infected macrophages by a constitutive exocytic event. AB - Bacterial cell wall constituents are released from mycobacterial phagosomes and actively traffic within infected macrophages. Colocalization of fluorescently tagged bacterial moieties with endocytic tracers revealed the dynamic movement of released mycobacterial constituents into the endocytic network with accumulation in tubular lysosomal-like compartments. The released bacterial constituents not only penetrated the infected host cell but were also present in an extracellular microvesicular fraction. To identify the intracellular source of these exocytic compartments, released vesicular material was isolated from culture supernatants by differential ultracentrifugation and characterized by Western blot and electron microscopy analyses. The presence of lysosomal membrane proteins and lysosomal proteases suggested that labeled mycobacterial cell wall constituents access a constitutive lysosomal exocytic pathway. An abundance of multilamellar extracellular compartments morphologically reminiscent of MHC class II-enriched compartments (MIIC) implicated a MHC class II transport pathway in the extracellular release of bacterial constituents. Increases in intracellular free calcium have previously been shown to trigger lysosomal exocytosis by inducing fusion of lysosomes with the plasma membrane. To test if an increase in calcium would stimulate exocytosis with release of mycobacterial constituents, infected macrophages were exposed to the calcium ionophore A23187. The ionophore triggered the release of a microvesicular fraction containing labeled bacterial moieties, implicating calcium-regulated lysosomal exocytosis as a trafficking pathway by which mycobacterial products are released from infected macrophages. PMID- 11211934 TI - Synaptotagmin 13: structure and expression of a novel synaptotagmin. AB - Synaptotagmins represent a family of putative vesicular trafficking proteins. With synaptotagmin 13, we have now identified a novel synaptotagmin, making this one of the largest families of trafficking proteins. Similar to synaptotagmins 3, 4, 6, 7, 9, and 11, synaptotagmin 13 is expressed at highest levels in brain but is also detectable at lower levels in non-neuronal tissues. Synaptotagmin 13 is composed of the canonical domains of synaptotagmins that include an N-terminal transmembrane region and two C-terminal cytoplasmic C2-domains (C2A- and C2B domain) and a connecting sequence between the transmembrane region and the C2 domains. Different from most other synaptotagmins, however, synaptotagmin 13 does not have an N-terminal sequence preceding the transmembrane region, and features an unusually long connecting sequence that is proline-rich. Furthermore, the C2 domains of synaptotagmin are degenerate and lack almost all of the residues involved in Ca2+ binding, suggesting that synaptotagmin 13 is not a Ca2+-binding protein unlike most other synaptotagmins. Our data demonstrate that synaptotagmins represent a larger and more complex gene family than previously envisioned. PMID- 11211935 TI - Distribution and localization of CMP-N-acetylneuraminic acid hydroxylase and N glycolylneuraminic acid-containing glycoconjugates in porcine lymph node and peripheral blood lymphocytes. AB - An immunohistochemical analysis was performed on paraplast-embedded sections of porcine lymph node with antibodies specific for CMP-N-acetylneuraminic acid hydroxylase (h-3 antibody) and glycoconjugate-bound N-glycolylneuraminic acid (Neu5Gc), which appears as a result of the hydroxylase reaction (a-Gc antibody). The observed localization of the enzyme in cells of the perifollicular zone, including lymphocytes, was reflected in a similar distribution of glycoconjugate bound Neu5Gc. This result confirms previous biochemical investigations on the role of the hydroxylase in regulating Neu5Gc biosynthesis in vitro on a histological level. An analysis of lymphocytes isolated from porcine thymus, spleen, lymph node and peripheral blood revealed differences in the amount of Neu5Gc in the various lymphocytes that correlated well with the activity of the hydroxylase determined in these cells. The largest amount of Neu5Gc and highest activity of the enzyme were detected in the peripheral blood lymphocytes (PBL). Immunohistochemical studies with a-Gc and h-3 antibodies on sections of paraplast embedded PBL showed that these antigens were located at the cell surface and in the cytosol, respectively. Ultrastructural immunocytochemistry with the h-3 antibody and immunogold labelling was used to investigate the subcellular localization of the hydroxylase. The enzyme was detected in the cytosol in the vicinity of the nuclear membrane and the outer membrane of mitochondria, in particular those close to the nucleus. The antigen was also detected on cytoplasmic tubular structures. In addition, a weak labelling of the Golgi apparatus was also observed occasionally. The possibility that this localization may be related to the availability of the substrate CMP-Neu5Ac and the redox partner cytochrome b5 is discussed. PMID- 11211936 TI - Retinoic acid-induced blr1 expression requires RARalpha, RXR, and MAPK activation and uses ERK2 but not JNK/SAPK to accelerate cell differentiation. AB - Upstream signaling requirements of retinoic acid (RA)-induced blr1 expression and downstream signaling consequences of blr1 over-expression in a human myeloid leukemia cell line demonstrate that mitogen-activated protein kinase (MAPK) signaling complexes are involved in both avenues. RA-induced myeloid differentiation and G1/G0 growth arrest of HL-60 cells is known to require the activation of the RARalpha and RXR retinoid receptors, as well as activation of the MAPK, ERK2. Transcriptional activation of the Burkitt's lymphoma receptor 1 (blr1) gene occurs early during RA-induced differentiation of HL-60 cells and requires these same three activating processes. The use of retinoid ligands that activate either the RARalpha or the RXR retinoid receptors revealed that blr1 mRNA induction was detectable only when both RARalpha and RXR were activated. Neither the RARalpha nor RXR selective ligands alone induced expression of blr1, but the combination of the two ligands induced the expression of blr1 to the same extent as RA. The MAPKK (MEK) inhibitor, PD98059, was used to determine whether extracellular signal-regulated kinase (ERK2) activation was necessary for induction of blr1 mRNA. PD98059 inhibited induced blr1 mRNA expression, due to RA or activated RARalpha plus RXR ligands, indicating that ERK2 activation is necessary for blr1 mRNA expression. Previous studies showed that ectopic expression of blr1 also caused increased MAPK activation, in particular ERK2, and subsequently accelerated RA-induced differentiation and G1/G0 growth arrest. Inhibition of ERK2 activation inhibited differentiation of blr1 transfectants, suggesting that the accelerated differentiation reflected blr1-enhanced ERK2 activation. The present data also demonstrate that ectopic expression of blr1 increased JNK/SAPK activity, but JNK/ SAPK activation was not needed for accelerated RA-induced differentiation and growth arrest. The results show that the signals known to be required for HL-60 differentiation, activated RARalpha, RXR, and ERK2, are necessary for blr1 mRNA expression. Downstream consequences of blr1 overexpression include enhanced MAPK signaling. PMID- 11211937 TI - Collagen-induced proMMP-2 activation by MT1-MMP in human dermal fibroblasts and the possible role of alpha2beta1 integrins. AB - Culture of human dermal fibroblasts within a three-dimensional matrix composed of native type I collagen fibrils is widely used to study the cellular responses to the extracellular matrix. Upon contact with native type I collagen fibrils human skin fibroblasts activate latent 72-kDa type IV collagenase/ gelatinase (MMP-2) to its active 59- and 62-kDa forms. This activation did not occur when cells were cultured on plastic dishes coated with monomeric type I collagen or its denatured form, gelatin. Activation could be inhibited by antibodies against MT1-MMP, by the addition of TIMP-2 and by prevention of MT1-MMP processing. MT1-MMP protein was detected at low levels as active protein in fibroblasts cultured as monolayers. In collagen gel cultures, an increase of the active, 60-kDa MT1-MMP and an additional 63-kDa protein corresponding to inactive MT1-MMP was detected. Incubation of medium containing latent MMP-2 with cell membranes isolated from fibroblasts grown in collagen gels caused activation of the enzyme. Furthermore, regulation of MT1-MMP expression in collagen cultures seems to be mediated by alpha2beta1 integrins. These studies suggest that activation of the proMMP-2 is regulated at the cell surface by a mechanism which is sensitive to cell culture in contact with physiologically relevant matrices and which depends on the ratio of proenzyme and the specific inhibitor TIMP-2. PMID- 11211938 TI - Effects of prolonged exposure to hypoxia on morphological changes of endothelial cells plated on fibrin gel. AB - Since tissue oxygenation has a profound effect on capillary growth, the effect of pO2 on endothelial cell functions was studied. Under normoxic conditions, EA.hy926 endothelial cells and HUVEC plated onto fibrin gels in low-serum culture medium underwent rapid and profound morphological changes within 12 to 48 hours depending on the cell line used. Their characteristic cobblestone organisation was transformed into a network of cord-like or tube-like structures. We showed that when exposed to low oxygen concentrations for 3 days, HUVEC and EA.hy926 have their ability to rearrange reduced to around 50 %. With EA.hy926 this effect was amplified by 79% after 9 days of hypoxia. The altered behaviour of hypoxia adapted cells was not caused by a loss in their fibrinolytic activity. In fact, the fibrin degradation rate and the generated fibrin fragments appeared identical in normoxia and hypoxia. Confocal microscopy and gel densitometry showed that in normoxia the remaining undegraded fibrin gel underwent a dynamic remodeling whereas in hypoxia it remained undisturbed. It is likely that hypoxia induces modification in the factors that integrate matrix information and cytoskeletal organisation in order to contract fibrin. PMID- 11211939 TI - Localization of protein kinase A and vitronectin in resting platelets and their translocation onto fibrin fibers during clot formation. AB - Physiological stimulation of platelets with thrombin brings about the release of protein kinase A (PKA) into the plasma. In human blood, this kinase singles out and phosphorylates vitronectin (Vn), a multifunctional regulatory protein, which was proposed to play an important role in the control of fibrinolysis. Here we present immuno-cytochemical evidence to show: (i) that intact platelets possess on their surface an ecto-PKA which can preferentially phosphorylate Vn; (ii) that in the resting platelet, both the catalytic and the regulatory subunits of PKA are present on the platelet surface, in the surface-connected canalicular system, and within the alpha-granules of the platelets; (iii) that the process initiated upon platelet activation, which leads to the formation of fibrin fibers and consequently forms the fibrin net, is accompanied by a translocation of PKA, of Vn, and of PAI-1 onto the fibrin fibers. We propose that the localization and the translocation of these proteins in the fibrin net, together with our finding that PKA phosphorylation of Vn reduces its grip of PAI-1, can unleash PAI-1 in its free form. The free PAI-1 can then assume its latent (non inhibitory) conformation, allow plasminogen activators to trigger the formation of active plasmin, and to initiate fibrinolysis. PMID- 11211941 TI - The production and clinical evaluation of macrophage colony-stimulating factor and macrophage chemoattractant protein-1 in human follicular fluids. AB - PROBLEM: In order to investigate the role of macrophage colony-stimulating factor (M-CSF) and macrophage chemoattractant protein-1 (MCP-1) in human ovulation, we measured the concentrations of M-CSF and MCP-1 in human follicular fluids (FFs) and correlated them with oocyte maturation. METHOD OF STUDY: The oocytes were obtained from the FFs of 46 women undergoing in vitro fertilization and embryo transfer (IVF ET). The concentrations of M-CSF and MCP-1 in the FFs were measured by enzyme-linked immunosorbent assay. In addition, granulosa cells obtained from the FFs of IVF patients were cultured and treated with forskolin and 12-O tetradecanoylphorbol 13-acetate (TPA) for 24 48 hr. RESULTS: Concentrations of M CSF and MCP-1 were significantly higher in the FFs than in the serum (P < 0.01). M-CSF concentrations tended to be higher, while MCP-1 concentrations were significantly higher in the FFs containing mature oocytes than in FFs containing immature oocytes (P < 0.05). The production of M-CSF was markedly increased over the basal level after treatment with forskolin (10 microM) for 24 (P < 0.02) and 48 hr (P < 0.01); however, the production of MCP-1 was unchanged. CONCLUSIONS: Our data suggest that M-CSF and MCP-1 may play an important role in human preovulatory processes and that M-CSF, in particular, may be regulated by cyclic adenosine monophosphate. M-CSF and MCP-1 may also be valuable biochemical markers in the evaluation of oocyte maturation. PMID- 11211940 TI - Dendritic cells derived from peripheral monocytes express endothelial markers and in the presence of angiogenic growth factors differentiate into endothelial-like cells. AB - CD14-positive monocytes obtained from human peripheral blood were cultured with GM-CSF and IL-4. During the early culture phase immature dendritic cells (DCs) developed which not only expressed CD1a, HLA-DR and CD86, but also expressed the endothelial cell markers von Willebrand factor (vWF), VE-cadherin and VEGF receptors Flt-1 and Flt-4. Further maturation of DCs was achieved by prolonged cultivation with TNFalpha. These cells showed typical DC morphology and like professional antigen-presenting cells (APCs) expressed CD83 and high levels of HLA-DR and CD86. However, if immature DCs were grown with VEGF, bFGF and IGF-1 on fibronectin/vitronectin-coated culture dishes, a marked change in morphology into caudated or oval cells occurred. In the presence of these angiogenic growth factors the cultured cells developed into endothelial-like cells (ELCs), characterized by increased expression of vWF, KDR and Flt-4 and a disappearance of CD1a and CD83. Addition of IL-4 and Oncostatin M also increased VE-cadherin expression, and the loosely adherent cells formed clusters, cobblestones and network-like structures. vWF- expressing ELCs mainly originated from CD1a positive cells, and VEGF was responsible for the decrease in the expression of the DC markers CD1a and CD83. In mixed leukocyte cultures, mature DCs were more potent APCs than ELCs. Moreover, Ac-LDL uptake, and the formation of tubular structures on a plasma matrix was restricted to ELCs. These results suggest that in the presence of specific cytokines immature DCs have the potential to differentiate along different lineages, i.e. into a cell type resembling ELCs. PMID- 11211942 TI - Involvement of mu-calpain in human sperm capacitation for fertilization. AB - PROBLEM: The distribution and physiological role of calpains in human sperm were investigated. METHOD OF STUDY: Semen collected manually from healthy donors was liquefied then centrifuged by percoll gradient centrifugation. After exposure to different concentrations of Ca2+ ionophore A23187, the samples were used for immunostaining sodium dodecyl sulfate polyacrylamide gel electrophoresis, and western blot analysis. It was speculated from the results of the study using calpain-specific inhibitors that calpain contributes to the sperm motility and acrosome reaction. RESULTS: With the anti-pro mu-calpain antibody, sperm were immunostained, whereas all were negative for anti-pro mu-calpain antibody binding. Stained sperm were classified into four types according to the staining pattern: acrosome type, equatorial segment type, whole head type, and neck and tail segments type. Western blot analysis of sperm homogenate revealed a single 80-kDa band using the anti-pro mu-calpain antibody, its dose-dependent reduction with Ca2+ ionophore A23187 suggesting activation by this treatment. In the presence of membrane permeable calpain inhibitors, sperm motility and acrosome reaction were significantly suppressed. CONCLUSION: These results indicate that mu-calpain may play pivotal roles in the process of fertilization of human sperm. PMID- 11211943 TI - Integrin pattern and effect on contraction in cultured testicular peritubular myoid cells. AB - PROBLEM: Neither the integrin pattern nor the biological functions of integrins have been extensively documented in human cultured testicular peritubular myoid cells (TPMC). The integrin pattern and the presence of some proteins of the immunoglobulin superfamily on human TPMC as well as the role of integrins in TPMC contraction were examined. METHOD OF STUDY: Integrin expression was evaluated by immunofluorescence and FACS analysis. To assess the role of integrin in TPMC contraction, human and rat cells were added to a collagen gel system and exposed to contractile stimuli. RESULTS: The immunofluorescence and cytofluorimetric analysis showed that human cultured TPMC express alpha1, alpha2, alpha3, alpha4, alpha5, alpha6, alphav, beta1, beta3, and beta4 integrin subunits, and significant amounts of intercellular adhesion molecule-1 (ICAM-1), whereas they do not present alpha4, beta2, beta7 subunits, nor intercellular adhesion molecule 2 (ICAM-2) and neural cell adhesion molecule (NCAM). The preincubation of human cells with an anti-beta1 mAb and of rat cells with a polyclonal anti-beta1 antibody inhibited TPMC contraction induced by different contractile stimuli. CONCLUSION: Our investigation documented a broad integrin pattern on human cultured TPMC as well as a role for integrins in human and rat TPMC contraction. PMID- 11211944 TI - Characterization of 80 kDa human sperm antigen responsible for immunoinfertility. AB - PROBLEM: An 80 kDa human sperm antigen (80 kDa HSA) has been identified by western blot technique using serum of an immunoinfertile woman as a probe. The 80 kDa HSA has been subsequently purified from sperm extract and investigated for antifertility effects. METHOD OF STUDY: The purified 80 kDa HSA was used to immunize adult male and female rats. Rabbit anti 80 kDa HSA antibodies were used for immunofluorescent and immunohistochemical staining to demonstrate the presence of 80 kDa HSA on the sperm and to investigate its tissue distribution. The N-terminal sequence of native 80 kDa HSA and the peptides obtained by its endoproteinase Lys-C was determined. RESULTS: Active immunization of male and female rats with 80 kDa HSA caused infertility in all the immunized animals. Immunofluorescent staining showed its localization on the head region of the human and rat spermatozoa. While immunohistochemical studies showed its localization in the testes and epididymis but not in other somatic tissues. Partial amino-acid sequence analysis showed no sequence homology with any of the known protein in the database. CONCLUSIONS: 80 kDa HSA is a promising candidate antigen for immunocontraception as it is characterized and found to cause infertility upon active immunization. specific to spermatozoa and is conserved. PMID- 11211945 TI - The carriage of pro-inflammatory cytokine gene polymorphisms in recurrent pregnancy loss. AB - PROBLEM: Recurrent pregnancy loss (RPL) affects 2-4% of couples, and remains largely unexplained. Recent studies have examined the role of cytokines in the maintenance of normal pregnancy, which is linked with an increased expression of Th2 cytokines. Overexpression of Th1 cytokines is associated with RPL. Knowing that functional polymorphisms exist for certain cytokines, it has therefore been suggested that women with RPL may have a genetic predisposition to overexpress Th1 cytokines. METHOD OF STUDY: The genes for interleukin-1 beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) carry functional gene polymorphisms. In both cases these are biallelic polymorphisms that can be detected by polymerase chain reaction followed by restriction fragment length polymorphism. The aim of this pilot study was to assess whether carriage of the rarer alleles (TNF*2 and IL-1B*2) could act as independent risk factors in recurrent miscarriage. RESULTS: We found an increased incidence in the carriage of TNF*2, more pronounced in those women with two or more miscarriages. Carriage of the IL-1B*2 either alone or in association with TNF*2 was not associated with recurrent miscarriage. CONCLUSION: There may be a role for these cytokine gene polymorphisms in RPL. PMID- 11211946 TI - TGFbeta2 in embryos with inborn anomalies: effect of maternal immunopotentiation. AB - PROBLEM: TGFbetas are among the main immunoregulatory molecules contributing to successful embryonic development. Besides, our and other studies revealed that maternal immunopotentiation has a potential to increase the resistance of the embryo to the teratogenic insult. This work was designed to evaluate: (1) whether the formation of teratogen-induced anomalies is accompanied by an altered pattern of TGFbeta2 expression in embryonic cells and (2) whether maternal immunopotentiation modifies the pattern of TGFbeta2 expression in embryos responding to the teratogenic insult. METHOD OF STUDY: Experiments were performed in embryos of ICR mice exposed to 15 and 40 mg/kg of a reference teratogen, cyclophosphamide (CP) on day 12 of gestation. A group of mice was immunopotentiated with xenogeneic rat splenocytes 21 hr before the beginning of mating. Embryos were examined for the occurrence of gross structural anomalies 24 and 72 hr after CP treatment. Then, immunohistohemistry and in situ hybrydization assays were used to evaluate the expression of TGFbeta2 protein and mRNA in the brain, face, limbs and liver of these embryos. RESULTS: No external anomalies were observed in embryos examined 24 hr after CP treatment. Embryos examined 72 hr after CP treatment at 40 mg/kg exhibited agnathia, micrognathia, kinky tail, phocomelia, but no signs of dismorphogenesis were observed in the liver at the organ level. A significant increase in the expression of TGFbeta2 mRNA was observed in cells, residing in the brain, face and limbs but not in the liver of CP-exposed embryos tested 24 hr after CP injection in both doses. The level of TGFbeta2 protein in these embryos did not differ from that of controls. In embryos tested 72 hr after CP injection in the high dose both TGFbeta2 protein and mRNA expression were found to be elevated. Maternal immunopotentiation while enhancing the embryo's resistance to CP practically abolished an elevated expression of the TGFbeta2 mRNA detected in tested organ structures of embryos of non-immunopotentiated CP treated mice 24 hr after CP injection in both the low and the high doses. Also, a significant decrease in the level of TGFbeta2 mRNA expression was observed in embryos of immunopotentiated mice examined 72 hr after CP treatment. CONCLUSIONS: The results of this work show a possible involvement of TGFbeta2 in the formation of teratogen-induced structural anomalies and suggest that the stimulation of the maternal immune system may realize its protective effect by normalizing the level of TGFbeta2 expression in teratogen targeted embryonic structures. PMID- 11211947 TI - Inhibition of murine sperm-oolemma binding by antibodies to an oocyte membrane (OM) antigen: implication in contraceptive vaccine development. AB - PROBLEM: The present study was conducted to investigate the oocyte membrane protein(s) that is involved in sperm binding in the mouse, and whether or not it can be used for the development of a contraceptive vaccine. METHOD OF STUDY: The zona-free oocytes were treated with Triton X-100 and the extract was analyzed for homogeneity in the sodium dodecylsulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) after staining with silver nitrate. The appropriate band of 50+/-4 kD, designated as OM antigen, was excised from the gel and used for the immunization. The female rabbits were immunized with the excised band per se and the female mice were immunized with the OM antigen after conjugation to keyhole limpet hemocyanin (KLH). The affinity-purified antibodies were analyzed in the enzyme linked immunosorbent assay (ELISA), immunoprecipitation procedure, western blot procedure, indirect immunofluorescence technique (IFT), and spermoolemma binding assay. Actively-immunized mice were analyzed for in vivo fertility. RESULTS: The Triton X-100 extract of zona-free oocytes predominantly showed a single protein band of 50+/-4 kD in the SDS-PAGE. Active immunization of female rabbits and of female mice with OM antigen raised high antibody titers (ELISA titer > 1:4096) that specifically recognized the OM antigen in the immunoprecipitation and Western blot procedures, and reacted with the oocyte in the IFT. These antibodies demonstrated a significant (P < 0.05) up to a complete block of sperm-oolemma binding in the in vitro binding assay. Binding of both the acrosome-intact and acrosome-reacted sperm was inhibited. Mice actively immunized with OM antigen also showed a significant reduction in vivo fertility as seen by the 9-day implants in uteri. Preliminary data indicate that the antibodies to OM antigen were tissue-specific and did not react with the specific band in any tissue extract in the western blot procedure. CONCLUSIONS: These results indicate that the OM antigen is involved in spermoolemma binding and constitute an attractive molecule that needs further investigation for examining its utility in the contraceptive vaccine development. PMID- 11211948 TI - TCRgammadelta + T lymphocytes in unexplained recurrent spontaneous abortions. AB - PROBLEM: It is generally accepted that the immune system and cellular immunity in particular are involved in the mechanisms affecting the outcome of gestation. In order to evaluate a putative role of lymphocytes in the immunological mechanisms of unexplained recurrent spontaneous abortions (URSA), we studied peripheral blood lymphocyte subpopulations in 244 women with URSA and 44 controls. METHOD OF STUDY: Direct immunofluorescence in whole blood with the appropriate combinations of monoclonal antibodies and flow cytometry was used. RESULTS: The study showed: a) a statistically significant increase of the mean CD4/CD8 ratio (2.12+/-0.84 vs 1.85+/-0.63, P = 0,039); b) a statistically significant decrease of the mean value of the percentage of CD5+ CD19+ lymphocytes (0.4+/-0.6 vs 1.4+/-0.78, P < 0.0001); and c) a statistically significant increase of the percentage of T lymphocytes expressing TCRgammadelta (4.68+/-3.19 vs 2.61+/-1.14, P < 0.0001). It should be noted that a statistically significant high number of women with URSA (72/195, 36.9%) showed an increased percentage of TCRgammadelta T cells (> or = 5%, where 5 equals the mean value + 2 standard deviations (SD) of the mean value of controls), whereas such a high percentage was not found in any control subject. CONCLUSIONS: It seems that women who experienced URSA comprise a heterogeneous population, as far as immunological parameters are concerned. At least in a subgroup of them, TCRgammadelta + T cells could be considered to play a role in the immune pathogenesis of fetal loss. PMID- 11211949 TI - Vitamin D, physical performance and disability in the elderly. PMID- 11211950 TI - Gender differences in morbidity and mortality related to depression: a review of the literature. AB - In this review of the existing evidence regarding a gender-specific association of depression with major health outcomes in older adults, we were unable to confirm that relative risk of morbidity and/or mortality due to depression varies with respect to gender. Future researchers may wish to concentrate their efforts in the identification of possible biophysiologic mechanisms underlying the association between depression and a variety of health outcomes. PMID- 11211951 TI - Sleep disordered breathing in the elderly. AB - Sleep disordered breathing (SDB), i.e., obstructive, central or mixed sleep apneas, has been recognized as a common occurrence in the elderly. Aging is per se associated with a decrease in the quality of sleep; SDB may further disrupt the sleep architecture in older subjects. The prevalence of obstructive sleep apnea (OSA) increases with aging; available studies report prevalence rates of 11 62%. Furthermore, OSA has been associated with increased mortality in older adults. Central apneas and periodic breathing occur with increased frequency either in subjects with neurological disorders such as infarction, tumor, sequelae of infection, diffuse encephalopathies, or in chronic heart failure. Patients with cerebrovascular disease (stroke, or transient ischemic attacks) have a markedly high prevalence of SDB, mainly OSA. In these patients, SDB is associated with a poorer functional prognosis at 3 and 12 months after the acute event, and a higher mortality. The clinical impact of SDB on cognitive function appears to be modest in patients without dementia, although there is a moderate increase in daytime sleepiness. In Alzheimer's disease (AD) however, SDB occurs more frequently than in non-demented older subjects, and its severity is correlated with the degree of cognitive impairment. The hypothesis of a causal relationship between AD and SDB remains a subject of controversy. The possibility of SDB should be considered in the elderly in the differential diagnosis of "reversible dementias", increased daytime sleepiness, or unexplained right-sided heart failure. PMID- 11211952 TI - Characteristics associated with inappropriate hospital use in elderly patients admitted to a general internal medicine service. AB - Our objective was to identify patient characteristics associated with inappropriate hospital days in a cohort of elderly medical inpatients. This prospective cohort study included a total of 196 patients aged 75 years and older, who were consecutively admitted over eight months to the internal medicine service of a regional, non-academic public hospital located in a rural area of Western Switzerland. Patients with severe cognitive impairment, terminal disease, or previously living in a nursing home were excluded. Data on demographics, medical, physical, social and mental status were collected at admission. A blinded hospitalization review was performed concurrently using a modified version of the Appropriateness Evaluation Protocol (AEP). Subjects' mean age was 82.4 years; 63.3% were women. Median length of stay was 8 days. Overall, 68 patients (34.7%) had at least one inappropriate day during their stay, including 18 patients (9.2%) whose hospital admission and entire stay were considered inappropriate. Most inappropriate days were due to discharge delays (87.10%), primarily to nursing homes (59.30%). Univariate analysis showed that subjects with inappropriate days were more likely to be living alone (69.1 vs 48.4%, p=0.006), and receiving formal in-home help (48.5 vs 32.8%, p=0.031). In addition, they were more impaired in basic and instrumental activities of daily living (BADLs, and IADLs, p<0.001 and p=0.015, respectively), and more frequently had a depressed mood [29.4 vs 10.9%, p=0.001 with a score > 6 at the Geriatric Depression Scale (GDS), short form]. Using multivariate analysis, independent associations remained for patients living alone (OR 2.6, 95%CI 1.2-5.8, p=0.016), those with a depressed mood (OR 2.8, 95%CI 1.1-7.3, p=0.032), with BADL dependencies (OR 1.5, 95%CI 1.2-1.8, p=0.001), and IADL dependencies (OR 1.3, 95%CI 1.0-1.6, p=0.032). Cardiovascular (OR 0.2, 95%CI 0.1-0.7, p=0.008) and pulmonary admission diagnoses (OR 0.1, 95%CI 0.0-0.7, p=0.022) were inversely associated with inappropriate hospital days. In conclusion, patients living alone, functionally impaired and showing depressive symptoms were at increased risk for inappropriate hospital days. These characteristics might permit better targeting for early discharge planning in these at-risk subjects, and contribute to avoiding premature discharge of other vulnerable elderly patients. Whether these interventions for at-risk patients will also result in prevention of hospitalization hazards, such as deconditioning and related functional decline, will require further study. PMID- 11211953 TI - Mini mental state examination in geriatric stroke patients. Validity, differences between subgroups of patients, and relationships to somatic and mental variables. AB - To study the validity of the Mini Mental State Examination (MMSE) in geriatric stroke patients, 116 patients were tested 2-8 weeks and 6 months post-stroke. A neuropsychological test battery consisting of five tests measuring memory, calculation and spatial ability was used for validation. Motor activity, depression, aphasia and activities of daily living were assessed. Confusion in the acute stage, Barthel Index, depression scores, level of motor activity, and most of the neuropsychological tests correlated to the MMSE. Logistic regression showed 4 independent variables which could predict the MMSE scores. A factor analysis showed 3 factors which could explain 53% of the variance. The sensitivity for detecting dementia was 56%, and increased to 68% if patients with isolated spatial dysfunction were excluded. The MMSE had acceptable validity in detecting cognitive dysfunction early poststroke in this old patient population. PMID- 11211954 TI - Age-related modifications in human unstimulated whole saliva: a biochemical study. AB - Human whole saliva contains a number of antimicrobial agents, and lysozyme, lactoferrin, secretory IgA and peroxidase are among the best known. Peroxidase catalyzes a reaction involved in the inhibition of bacterial growth and metabolism, and the prevention of hydrogen peroxide accumulation, thus protecting proteins from the action of oxygen and reactive oxygen species (ROS). To better understand the role played by the oxidative stress in the aging process, we studied the relationship between total protein content, peroxidase activity, malondialdehyde (MDA) and nitric oxide (NO) content of human unstimulated whole saliva in 169 healthy subjects subdivided into groups according to age. Our results show a significant decrease in peroxidase activity with age. Moreover, the increase in saliva lipid peroxide levels indicates an enhanced free radical production that may contribute to tissue damage. On the other hand, findings concerning human unstimulated whole saliva NO content showed a significant increase in elderly subjects, suggesting that an enhanced NO production might depend on a stimulation of leukocyte-inducible NO synthase (i-NOS) activity. Our results suggest that during aging the oral tissues may become more susceptible to environmental factors due to a modification in the balance between different antimicrobial agents. PMID- 11211956 TI - Muscle strength, functional mobility and vitamin D in older women. AB - Vitamin D deficiency may lead to loss of type II muscle fibres, and thereby to atrophy of proximal muscles with an increased risk of falling and bone fractures. The aim of the study was to determine if six months of vitamin D treatment (0.5 microg alphacalcidol) could positively influence values for muscle strength and functional mobility in vitamin D-deficient older women. Twenty-seven women entered the study which took place at a teaching hospital outpatient department. Ten vitamin D-deficient (serum 25(OH)D3 <20 nmol/L) older (>70 years) women and 13 age-matched female subjects with normal vitamin D levels (serum 25(OH)D3 >30 nmol/L) completed the study. Preand post-treatment data were obtained for isometric knee extensor strength, handgrip strength and functional mobility (walking distance over 2 minutes and the timed i'Up & Go" test). Six months of treatment with alphacalcidol led to significant improvements (compared to the controls) in values of isometric knee extensor strength (left leg: 14.6% +/- 5.7%. p=0.03; right leg: 11.5% +/- 5.0%, p=0.02) (mean +/- SEM). The achievements in the timed "Up & Go" test and 2-minute walking test did not improve in the alphacalcidol group compared to the controls after 6 months. However, within the vitamin D-deficient group, 6 months of alphacalcidol treatment led to a significant increase in the walking distance over 2 minutes (increase from 137.6 +/- 12.6 to 151.3 +/- 11.2 meters, p=0.03). The controls, with normal vitamin D levels, did not exhibit improvements in performance of any of the tests over a period of 6 months. Summarized, alphacalcidol seems to improve muscle strength and walking distance over 2 minutes in vitamin D-deficient older women. PMID- 11211955 TI - Factors relating to place of death of Japanese people from a small town in a rural area. AB - The objective of our retrospective study was to clarify factors relating to place of death of Japanese people from a small town in a rural area who had been bedridden for at least one week before dying. The caregivers of subjects aged 40 and above who died during a three-year period were surveyed by trained interviewers. Of 352 subjects who died, 312 caregivers responded and agreed to a face-to-face interview. A total of 213 subjects were considered as an eligible sample. The main outcome measures were odds ratios for death at home in relation to age, pain, cause of death, and home visit service. One hundred and two people died at home, while 112 people died in a hospital. Multivariate logistic regression analysis showed that the probability of home death increased with age of the bedridden, lack of pain during the bedridden period, not having cancer as a cause of death, having senility as a cause of death, and receiving regular home visits by a Public Health Nurse. In conclusion, expansion of the home visit programs by Public Health Nurses may enable people to die at home as they so desire. Further prospective research is needed to explore the association between the attitude toward terminal care and the place of death. PMID- 11211957 TI - A test of recently proposed BMI standards with respect to old age. AB - The purpose of this study was to investigate the effects of age on the relationship between BMI and multiple coronary risk factors, and to determine whether the BMI classification by NHLBI and WHO is applicable as a predictor of coronary risk factors in older (>65 years) as well as in younger (<65 years) men and women. Effects of age on ten coronary risk factors were examined. Sex differences in the slopes of BMI on risk factors were compared between younger and older subjects in order to examine the effects of age on these relationships. The frequency of risk factor abnormality in individual BMI groups (18.5-24.9, 25.0-29.9, 30.0+) was examined for four age-sex groups. The significance of an age group-BMI interaction term was tested by the logistic regression model to see whether there is a significant difference in the relationship between BMI and the individual risk factor abnormalities between younger and older subjects. Older subjects had significantly higher values for most risk factors than younger subjects. The slopes of BMI on risk factors were different between younger and older subjects for fasting glucose, total, HDL- and LDL-cholesterol in men, and for diastolic blood pressure, total and LDL-cholesterol in women. The proportion of subjects with abnormal risk factor levels in each of the three BMI groups was higher in older than in younger subjects for most risk factors. There was generally a progressive worsening of the risk factor levels with increasing BMI in both age groups. There was no consistent age difference in the relationship between BMI groups and the frequency of risk factor abnormality. We conclude that, although age increases the frequency of most cardiovascular risk factor abnormalities, in general, it does not affect the trend of the relationship between the risk factors and the normal, overweight and obese BMI groups defined by NHLBI and WHO. Therefore, these BMI categories are applicable as predictors of risk factor levels in older as well as in younger men and women. PMID- 11211958 TI - Glutathione deficiency potentiates manganese-induced increases in compounds associated with high-energy phosphate degradation in discrete brain areas of young and aged rats. AB - Aging is a factor known to increase neuronal vulnerability to oxidative stress, which is widely accepted as a mechanism of manganese-induced neuronal damage. We previously showed that subchronic exposure to manganese induced greater energy impairment (as revealed by increases in hypoxanthine, xanthine and uric acid levels) in the striatum and brainstem of aged rats vs young rats. This study shows that inhibition of glutathione (GSH) synthesis, by means of buthionine (SR) sulfoximine, decreased GSH levels and increased the ascorbic acid oxidation status in the striatum and limbic forebrain of both young and aged rats. In addition, inhibition of GSH synthesis greatly potentiated the manganese-induced increase in inosine, hypoxanthine, xanthine and uric acid levels in both regions of aged rats; moreover, inhibition of GSH synthesis significantly increased inosine, hypoxanthine, xanthine and uric acid levels in both regions of young rats, compared with the manganese-treated group. These results suggest that an impairment in the neuronal antioxidant system renders young rats susceptible to manganese-induced energetic impairment, and further support the hypothesis that an impairment in this system plays a permissive role in the increase of neuronal vulnerability that occurs with aging. PMID- 11211959 TI - Changes in force by repeated stretches of skeletal muscle in young and old female Sprague Dawley rats. AB - We examined whether the decline in isometric force and peak stretch force during repeated stretches of activated plantar flexor muscles was larger in old (24 months, N=5) compared with young (4 months, N=5) female Sprague Dawley rats. Thirty stretches were imposed on isometric contractions (stimulation time 1.9 s, rest periods 180 s) by ankle rotation from 90 degrees to 40 degrees at 50 degrees x s(-1). Even though muscle weights were similar [2094 +/- 54 (young) vs 2033 +/- 73 mg (old) (mean +/- SE)], the isometric force (IF) at 90 degrees before stretch 1 and peak stretch force (PSF) at 40 degrees for stretch 1 were lower in old rats [18.9 +/- 0.5 vs 15.5 +/- 1.4 N (p=0.024) and 25.8 +/- 1.3 vs 20.5 +/- 0.9 N (p=0.017)]. After the stretches, the IF deficit was similar [38.5 +/- 3.0% (young) vs 39.8 +/- 3.4% (old)] and did not recover after 1 hour of rest [35.1+/- 4.1% (young) vs 36.9 +/- 4.3% (old)]. The decline in PSF was/also similar [36.0 +/- 5.2% (young) vs 26.6 +/- 1.8% (old)]. Skeletal muscles of 24-month-old female Sprague Dawley rats were weaker than 4-month-old rats but had similar susceptibility to develop IF deficits after stretches of activated muscles. PMID- 11211960 TI - Parental imagery vividness: gender differences and relationships to emotional closeness. AB - This research was an investigation of the vividness with which individuals see their parents in different situations. In 3 studies, the Vividness of Visual Imagery for Parents Questionnaire (VVIPQ; S. J. McKelvie, 1998a) was completed by university undergraduates (201 women, 167 men). Visual imagery of mothers was reported to be more vivid than that of fathers, but only by the female students. For intact families, the female students also reported more imagery of mothers than of fathers, whereas the male students reported more vivid imagery of fathers than of mothers. However, for divorced or separated families in which individuals spent more time with their mothers, both men and women rated their mothers more vividly than their fathers. More vivid imagery was positively related to reported emotional closeness to parents and to more vivid imagery for general scenes. VVIPQ scores were associated with social desirability but were not related to measures of response leniency or general intelligence. Split-half reliability of the VVIPQ was very good, and both test-retest and alternate-format reliability were acceptable. The correlational evidence supports the construct validity of the VVIPQ, which is a promising tool for studying parental imagery. PMID- 11211961 TI - An operations model of psychosocial structure and function and of psychotherapy. AB - Currently, personality theory and clinical psychology have a fairly substantial tradition of promoting a strongly scientific basis for clinical work and theorizing. However, an appropriate foundation model has been difficult to identify and establish. A theory of human operations, here proposed, may provide such an elementary model. The theory is rooted in the organizational and industrial field known as operations, which is a highly systematic, precise, flexible, scientific approach to the understanding and management of human goal seeking action in the broadest sense. The proposed model includes the classical humanistic, clinical, and decision theoretic notions of values, cognition, emotions, ego, behavior, objectives, outcomes, feedback, and defenses. These notions are placed within an overall operations frame of reference and developed in such a manner that they can be used to assess human clinical problems and to design therapeutic interventions. The strengths and limitations of the model are discussed. PMID- 11211962 TI - Interpersonal conflict and sarcasm in the workplace. AB - Violence and aggression in the workplace are problems that most Americans confront on a daily basis. The present study is an exploration of the predisposition to conflict in a work environment in which personality traits responsible for increased sarcasm and increased anger in response to sarcasm are identified. Participants represented two subdepartments within a city general hospital. The Keirsey Temperament Sorter (D. Keirsey, 1998) test for departmental temperament and a sarcasm survey designed by the author were used to test for frequency of sarcasm and anger in relation to differing categories of sarcasm. Angry reactions were gauged in relation to sarcasm directed at job performance, personal life, behavior, and appearance. Conclusions from this study point to many variables as causes for workplace anger; these include influences from organizational culture, work environment, psychological defense mechanisms, leadership decisions, stress, task orientation, and personality differences. Sarcasm trigger points leading to anger may be predicted based on a work group's personality composition. A homogeneous personality composition within a work group may involve factors such as personality characteristics common to a particular profession, organizational demands, and hiring practices. PMID- 11211963 TI - Giant cell arteritis. Epidemiology, etiology and pathogenesis. AB - Giant cell arteritis (GCA) is a chronic inflammatory disorder targeting large and medium-sized arteries, which predominantly affects postmenopausal women. Its high incidence in populations with Scandinavian lineage, some familial accumulation, and the association with the HLA-DR4 haplotype indicate a genetic predisposition. Epidemiological observations, as well as the symptomatology, may indicate an infectious origin, but so far GCA has not been shown to be a truly infectious form of vasculitis. Immunological research indicates an antigen-driven disease with local T-cell and macrophage activation in the vessel wall. Morphologically, the inflammatory process appears to be initiated by a foreign-body giant-cell attack on calcified internal elastic membrane in arteries and on calcified atrophic parts of the aortic media. The ensuing diffuse chronic inflammation leads to vessel dilatation and extensive intimal thickening. The latter, which relates to the production of promoting factors by the inflammatory cells, causes arterial stenosis and ischemic complications. The possible role of female sex hormones in GCA requires further investigation. Mononuclear and giant cells in GCA display the cytoplasmic accumulation of estrogen receptor (ER) alpha. Cytoplasmic ER-alpha is also seen in media smooth-muscle cells in GCA and in non GCA controls, but nucleotide sequence analysis of the ER-alpha gene revealed no differences between GCA patients and controls. In the future, comprehensive morphological, cell biological and immunological research will be required for a better understanding of the complex etiology and pathogenesis of GCA. PMID- 11211964 TI - Retesting and follow-up of first-catch urines from men yield variable results with three Chlamydia trachomatis nucleic acid amplification tests. AB - First-catch urines from 276 asymptomatic male military recruits were screened by polymerase chain reaction for the detection of Chlamydia trachomatis. Eight initially positive specimens were retested by polymerase chain reaction, ligase chain reaction and transcription-mediated amplification. Urine specimens from six (2.2%) subjects were considered to contain C. trachomatis. However, retesting of serially collected urines from five of these six subjects using different nucleic acid amplification methods showed some discrepancy. This may have a major impact on the efficacy of screening programs for C. trachomatis in low prevalence populations. PMID- 11211965 TI - Buffy coat PCR for diagnosis of experimental pneumococcal pneumonia. AB - An immunocompetent murine model of pneumococcal pneumonia and bacteremia was used to evaluate a PCR assay based on amplification of the pneumolysin gene. Mice were treated with trovafloxacin to determine the decline in sensitivity of PCR as lung bacterial concentrations decreased and blood cultures became sterile. Forty-three mice were studied for up to 120 h after start of antibiotic treatment. PCR of buffy coat specimens was more sensitive than PCR of plasma. Only 21% of animals had a positive blood culture, whereas 77% of PCR buffy coat assays were positive. After 48 h of therapy all blood culture specimens were sterile, whereas buffy coat PCR was positive in 57.8% of specimens. PCR of buffy coat specimens was negative in all mice colonized nasally with Streptococcus pneumoniae and in rabbits with Escherichia coli bacteremia. Our results demonstrate that our PCR technique using buffy coat specimens is highly specific for invasive pneumococcal disease and remains positive in the majority of animals for at least 48 h after start of antibiotic therapy. PMID- 11211966 TI - Comparison of nasal swab culture, quantitative culture of nasal mucosal tissue and PCR in detecting Streptococcus pneumoniae carriage in rats. AB - It is not known how well nasopharyngeal swab culture represents pneumococcal carriage status. We tested this by comparing swab culture to quantitative culture and quantitative PCR of mucosal tissue in a rat model of pneumococcal carriage. Quantitative culture and quantitative PCR identified significantly more carriers compared to swab culture (differences 15% and 33%, 95% CI 1-28% and 16-47%, p=0.04 and 0.001, respectively). The sensitivity and specificity of swab culture was 75/92% and 63/100% compared to quantitative tissue culture and quantitative PCR, respectively. The quantitative estimates of culture and PCR were very similar (Pearson correlation coefficient 0.79, p<0.001). In conclusion, even a well-controlled swab sampling markedly underestimates pneumococcal carriage rate, and simultaneous use of quantitative culture and PCR increases the number of positive samples by about one third. PMID- 11211967 TI - Hepatitis C virus genotypes in Estonia. AB - Distribution of hepatitis C virus (HCV) geno(sub)types among 215 Estonian patients hospitalized with acute or chronic hepatitis and with HCV RNA-positive sera was investigated. For genotyping, both multiplex PCR with subtype-specific primers of the core region and RFLP analysis of cDNA of the 5' NCR region were used. These two methods permitted a correct characterization of genotypes, a more truthful characterization of mixed infections, and combined use of single-tube performances. They revealed, respectively, 200 and 202 (93.0% and 93.9%) HCV positive samples of sera, subtype 1a- 0.9% and 0.9%, 1b- 56.3% and 64.2%, 3a- 13.9% and 22.3%, 2a- 6.5% and 5.6%, type 4 0.5% and 0%, mixed infections- 13.5% and 0%, and unidentified- 1.4% and 0.9%. In the majority of cases (84.7%) both methods gave completely or partially concordant results; in mixed infections, as determined by subtype-specific PCR, only one subtype was revealed by the RFLP method. In the remaining 15.3% of the cases (Ohno- 7.0%, RFLP- 8.3%) only one of the methods was positive. The epidemiological analysis of the dynamics of the subtypes' relative participation may indicate increasing 3a and decreasing 1b subtype infection during recent years. PMID- 11211968 TI - Expression and localisation of IGF-binding protein mRNAs in regenerating rat skeletal muscle. AB - The expression of the insulin-like growth factor-binding proteins (IGFBP) -3, -4, -5 and -6 was investigated in neonatal, in normal adult and in regenerating rat skeletal muscle. Semi-quantification was done by densitometric scannings of Northern blots. The expression of all investigated IGFBPs, with the exception of IGFBP-5, was higher in neonatal than in adult muscle. During postischaemic regeneration the expression of all IGFBPs increased, but with different time schedules. IGFBP-3 increased transiently during the early phase of regeneration, while IGFBP-4, -5 and -6 increased during the later phase of regeneration. In situ hybridisation on regenerating muscle showed that the expression of the various IGFBPs was cell specific; thus, IGFBP 3 was mainly expressed in macrophages, IGFBP-4 in connective tissue, IGFBP-5 in regenerating muscle cells, and IGFBP-6 in muscle cells, connective tissue and endothelium. Ligand blotting, using 125I-IGF-I as the ligand, showed a number of bands ranging between 24 and 44 kDa. Samples from neonatal and regenerating muscle contained much higher levels of all IGFBPs than those from normal adult muscle. An ordered and cell specific expression of IGFBPs, allowing a strict regulation of IGF actions, is probably necessary to ensure an optimal regeneration process. PMID- 11211969 TI - p53 and Bcl-2 oncoprotein expression in placentas with hydropic changes and partial and complete moles. AB - Forty molar and non-molar placentas with hydropic changes (14 complete moles, 14 partial moles, and 12 hydropic non-molar placentas) were examined immunohistochemically for expression of oncoproteins p53 and Bcl-2. The data were evaluated to determine if p53 and Bcl-2 expression could aid in differentiating molar from non-molar pregnancies on the one hand and complete mole from partial mole on the other. Thirteen out of fourteen complete moles showed p53 expression (93%), 8 of the 14 partial moles expressed p53 (57%), and none of the non-molar pregnancies expressed p53 in the extravillous intermediate trophoblasts. Regarding Bcl-2, the syncytiotrophoblasts of most molar and non-molar placentas showed strong and diffuse positivity. These results suggest that p53 expression can be used as a distinguishing parameter between complete moles and placentas with hydropic changes on the one hand and to a lesser extent between partial moles and placentas with hydropic changes on the other hand. Bcl-2 cannot be used in the same way as p53. PMID- 11211970 TI - Prevalence of EHEC O157:H7 in patients with diarrhoea in Lagos, Nigeria. AB - The prevalence of sorbitol-nonfermenting Escherichia coli O157:H7 (EHEC) was assessed in 100 patients with diarrhoea by stool culture on sorbitol MacConkey agar. The cytotoxicity of the EHEC strains was analysed by Vero cell assay and the antimicrobial susceptibility pattern of the isolates was determined. Detection rate of EHEC O157:H7 was 6%. Five of the six patients were males. Three of the isolates were from children and one was from a teenager. All strains induced cytotoxic effects in the Vero cell assay. All isolates were susceptible to most of the antimicrobials tested. The results showed that diarrhoea caused by EHEC O157:H7, a potentially life-threatening pathogen, has remained common particularly among the child population of Lagos during the past 10 years (5). There must therefore be adequate meat and food inspection to improve the general hygiene of local fast food restaurants, so-called 'bukkas', which are regarded as likely sources of infection. PMID- 11211971 TI - Autoantibody activity of the immunoglobulin secreted by a follicular B-cell lymphoma. AB - In patients with B-cell lymphoma, only in rare cases a secreted paraprotein is found, and in very few of them an associated autoantibody activity has been demonstrated. Here we report the case of a patient with a low-grade B-cell lymphoma with a serum biclonal paraprotein (G,M)lambda and severe erythroblastopenia. Indirect immunofluorescence studies of total serum revealed cytoplasmic (Hep-2 cells) and extracellular matrix (rat tissue sections) staining, suggestive of a new specificity. After gel filtration of serum samples, only the IgM-containing fraction showed the same pattern of staining. Tumor derived hybridomas expressed an unmutated V3-11 gene identical to that found in tumor samples and secreted an IgM immunoglobulin endowed with the same reactivity, which confirms the tumoral origin of the tissue-reactive protein. The results suggest a link between the autoimmune condition in this patient and the novel specificity displayed by the tumor-derived immunoglobulin. PMID- 11211972 TI - Distribution and sequence variations of selected virulence genes among group A streptococcal isolates from western Norway. AB - In order to compare the distribution of selected virulence genes among group A streptococci recovered from invasive disease and superficial infections, 42 isolates were screened for mga, speB, speA, ssa and ska, by PCR. The isolates were predominantly of the sequence types emm1, emm3 and emm6, but also included a few of the types emm22, emm28, emm75 and emm78. The phage-mediated speA seemed to be prevalent in emm types 1 and 3, and its distribution was not related to disease severity. The other genes were present in all isolates. The mga, speB and speA were further studied by sequence analysis. Although allotypic associations with invasiveness were not found, allelic specificity to the emm sequence type was observed. In addition, the mga sequences indicated two lineages, related to opacity factor production. A possible recombination between these two main divergent mga genes was observed in isolates of the types emm22 and emm75. A logical nomenclature of the alleles of mga and speB is suggested. PMID- 11211973 TI - Structural evidence for counter-current flow in proximal tubules versus pertitubular capillaries in the rat kidney. Evaluation of the counter-current mechanism between the proximal convoluted tubules and the peritubular capillaries in the rat nephron. AB - BACKGROUND: In spite of the very high exchange of water and solutes between the proximal tubules and the peritubular capillaries, very little is known about flow directions in these two interrelated structures. We therefore developed a morphological technique suitable for the quantitative evaluation of a counter current system between the proximal convoluted tubules and the peritubular capillaries in rat renal cortex. METHODS: In male pentothal-anesthetized Wistar rats (body weight 200-250 g), India ink was injected into the aorta above the renal arteries, followed by instant freezing of the right kidney in isopentane at -165 degrees C, and subsequent freeze-substitution in alcohol. In microscopic slides from kidneys in which only 20-55% of the cortical peritubular capillary loops was filled with ink--representing the arterial end of the capillaries--and in which the proximal tubular segmentation could be identified in PAS-stained sections, the segments of the convoluted proximal tubules were quantitatively compared with regard to the presence of ink-stained and unstained peritubular capillaries in nephrons from the whole renal cortex. RESULTS: In the microscopic specimens of the five animals used both the loops from the first segment (P1) of the proximal convoluted tubule and those of the second segment (P2) were systematically packed closely together, the transitional segment (P1-2) being interposed between the groups. Around the loops of P1, 8%+/-2% of the capillaries was stained with India ink. In contrast, surrounding the P2 loops 67%+/-5% of the capillaries contained ink, significantly exceeding that for P1 (p<0.01). CONCLUSION: Throughout the rat renal cortex, the most proximal fraction of the peritubular capillaries surrounds the second segments of the proximal convoluted tubules, while the first tubular segments are surrounded by the more distal fraction of the peritubular capillaries. Consequently, the flows in the peritubular capillaries and in the proximal convoluted tubules in the rat renal cortex are systematically arranged as a counter-current system. This feature was previously identified only in superficial nephrons. PMID- 11211975 TI - Effects of electromagnetic radiation of the millimeter wavelength range on catecholamine metabolism in patients with arterial hypertension. PMID- 11211974 TI - Immunohistochemical localization of inducible and endothelial constitutive nitric oxide synthase in neoplastic and autoimmune thyroid disorders. AB - AIM: To investigate the distribution of nitric oxide synthase in tissues derived from patients with autoimmune or neoplastic disorders of the thyroid gland in order to test whether the expression of inducible nitric oxide synthase or endothelial constitutive nitric oxide synthase (two subtypes of EC 1.14.13.39) may be related to the inflammatory activity or degree of neoplasia. EXPERIMENTAL DESIGN: The expression of nitric oxide synthases was examined by immunohistochemistry in tissues from patients with either Hashimoto's thyroiditis (n=6), hyperplastic glands (Graves' disease) (n=7), adenomas (n=8), multinodular goitres (n=7), papillary carcinomas (n=4) or follicular carcinomas (n=5). RESULTS: Expression of inducible nitric oxide synthase was found in 22 of the tissues and was not specific for any of the examined thyroid disorders. Expression of endothelial constitutive nitric oxide synthase was found in some of the epithelial cells in all the tissues. There was no correlation between the intensity and distribution of the immunostaining and the thyroid disorders. CONCLUSION: Demonstration of nitric oxide synthase cannot be used for diagnostic purposes. The expression of endothelial constitutive nitric oxide synthase in all tissues indicates that the enzyme may be of importance for the function or growth of the thyroid epithelial cells. PMID- 11211976 TI - Rheocardiomonitoring systems. PMID- 11211977 TI - Clinical efficacy and immunoregulatory and neurohumoral effects of MM therapy in patients with atopic dermatitis. PMID- 11211978 TI - Laser clinical diagnostics as a promising trend of biomedical radio electronics. AB - This article outlines the up-to-date achievements of laser noninvasive clinical diagnostics. The outlook for its development and its close connection with the problems of physics, mathematics, and the electronic instrument-making industry are shown. The combined application of these disciplines in biology and medicine creates a novel integrated trend--medical physics. PMID- 11211979 TI - Prospects for applying fluorescence spectroscopy to diagnose the hard tissues of a tooth. AB - This article deals with the autofluorescence spectra from the hard tissues of a tooth, both in norm and pathology. An investigation was made on 30 extracted human teeth. The measurements were made both for the intact hard tissues of a tooth, such as enamel, dentine, cementum, and root canal, and for the tissues pathologically affected by a caries (superficial, intermediate, and deep) and by a dental calculus. It was found that the fluorescent spectra from enamel, dentine, cementum, and from the regions affected by a caries and dental calculus were identical in form. All the spectra revealed a maximum near 700 nm. However, the intact and affected hard tissues were greatly different in the integral fluorescent intensity. Dental calculus was found to produce the most pronounced fluorescent intensity, whereas the carious regions produced a slightly weaker fluorescent intensity. On the contrary, the intact hard tissues of a tooth exhibited the poorest fluorescent intensity. PMID- 11211980 TI - Fluorescence spectroscopy application in the express-evaluation of the gastrointestinal microflora. AB - Possible application is studied for fluorescence spectroscopy in the express evaluation of the gastrointestinal microflora. This diagnostic approach is feasible because of the difference in fluorescent spectra from different microorganisms, with anaerobic microorganisms exhibiting the most pronounced fluorescence. It was found that fluorescence strength raised with an increase in the bacteria Bacteroides and bifid bacteria, whereas it decreased with an increase in Escherichia coli. The bacteria Bacteroides and bifid bacteria are the most typical representatives of anaerobic bacteria, whereas the bacteria Escherichia coli are the typical representatives of aerobic bacteria. According to the literature, Bacteroides and bifid bacteria reveal an intense fluorescence. Bearing in mind that these genera of bacteria play an important role in the gastrointestinal microbiocenosis, fluorescence spectroscopy can be used as a diagnostic means for gastrointestinal dysbacteriosis. PMID- 11211981 TI - Features of electromagnetic radiation time-and-frequency fluctuation intensity distributions from human brain structures. AB - Time-and-frequency fluctuation intensity distributions' analysis is made of the electromagnetic radiation obtained from deep human brain structures. The role of monitoring the distribution changes due to various cerebral circulation disorders is explained. PMID- 11211983 TI - Millimeter radiation in the rehabilitation of oncological patients. PMID- 11211982 TI - The use of millimeter wavelength radiation to treat degenerative-dystrophic changes in articular cartilage in deforming osteoarthrosis. PMID- 11211984 TI - Functioning mechanisms of water biosensors of electromagnetic radiation. AB - The effect of microwaves on liquid water was investigated by using biosensors and physiochemical techniques, such as nuclear magnetic resonance (NMR) and spectrophotometry. The results obtained provided evidence for a nonthermal effect of microwaves on liquid water. PMID- 11211985 TI - Effects of millimeter wavelength electromagnetic radiation on neurons: electrophysiological study. PMID- 11211986 TI - Novel concepts of the causes of EHF-radiation-induced stimulating effects. AB - This article reviewed our investigations and the literature on the interaction of EHF radiation with biological objects. This allowed us to advance the general mechanism for the effect of millimetric waves on photosynthesizing organisms. PMID- 11211987 TI - Hydroxyapatite and their use as coatings in dental implants: a review. AB - At present, no standard manufacturing guideline exists for depositing hydroxyapatite (HA) on implant surfaces. Although animal and in vitro studies have reported on the benefits of using HA-coated implants as well as the risks of dissolution, these short-term studies did not demonstrate that the dissolution of the HA coating leads to a loss of implants. In addition, many in vivo and clinical studies did not include the chemical and structural characterization of the coatings, and thus comparisons between studies are difficult. In the clinics, the recommendation is that HA-coated screw implants be used for the anterior maxilla and posterior mandible where the bone depth exceeds 10 mm and when the cortical layer is thinner and spongiosia is less dense. In the posterior maxilla or when the cortical layer is very thin with low density, the use of HA-coated cylindrical implants is recommended. However, there are concerns for using HA coated implants. The clinician needs to take into consideration the enhanced bacterial susceptibility of HA coatings compared with titanium implants. In addition, the clinician needs to consider the possible failure of HA coatings as a result of coating-substrate interfacial fracture. Finally, besides the surgical skills, it is also important that the clinical investigators be well versed with the materials characterization needed for HA-coated implants, the problems associated with the current HA coatings, and the indications for use. In addition, the correlation between well characterized coatings and their effect on bone formation rate and long-term implant success, coating-implant interfacial strength, and alternative superior coating process need to be investigated further. PMID- 11211988 TI - The role of charge transport in the reception of electromagnetic radiation. PMID- 11211989 TI - Investigating the influence of electromagnetic radiation from millimeter ranges on the cardiovascular system in the hypertensive rat. PMID- 11211990 TI - Microprocessor systems for self-control of vital bodily functions. AB - This article presents a fundamentally novel approach to an urgent medico-social problem of providing the timely medical care. To maintain people's health and life in their everyday activities, a new concept of the medical instrument-making industry was put forward. This concept was developed in terms of the theory of functional systems, which revealed the universal rules of self-regulation of bodily functions. The practical realization of the above-mentioned concept involved the construction, patenting, and production of a number of original devices capable of warning the patient about disorders in basic bodily functions. These devices included a Heart Protection System, a Stress Doser, a Physiological Clock, a Ration Controller, and a Mother-Fetus Controller. They can all be regarded as informational household microprocessor-based instruments of the 21st century. PMID- 11211991 TI - Epigenetic mechanisms of chemical carcinogenesis. AB - Chemically induced cancer is a multi-step process involving damage to the genome initially followed by clonal expansion of the DNA damaged cell eventually leading to a neoplasm. Chemical carcinogens have been shown to impact at all of the stages of the tumorigenesis process. It has become apparent that chemical and physical agents that induce cancer may do so through several different cellular and molecular mechanisms. Epigenetic (nongenotoxic) chemical carcinogens are those agents that function to induce tumor formation by mechanisms exclusive of direct modification or damage to DNA. These agents appear to modulate cell growth and cell death and exhibit dose response relationships between exposure and tumor formation. The exact and/or exclusive mechanisms by which these agents function have not been established, however, changes in cell growth regulation and gene expression are important to tumor formation. This review focuses on several potential mechanisms and cellular processes that may be involved in nongenotoxic chemical carcinogenesis. PMID- 11211992 TI - Safety assessment for non-genotoxic rodent carcinogens: curves, low-dose extrapolations, and mechanisms in carcinogenesis. AB - The most frequent biologic events associated with multispecies multisite rodent non-genotoxic carcinogenesis include robust liver P450 enzyme induction without liver toxicity. This cancer process is not relevant for humans as exemplified by phenobarbital. A host of other pharmaceuticals, including loratidine and atorvastatin, with current sales in the billions of dollars attests to the lack of relevance of our rodent models acting via this specific process. Hopefully, the mechanism of phenobarbital will no longer draw research money in further probing the irrelevant in human carcinogenesis. The known human carcinogens not linked with genetic injury all perturb tissue growth/replication in humans as well as in rodent short-term tests at doses ultimately linked with cancer. Clearly identifying exposures perturbing growth/replication versus exposures not perturbing growth provides an effective tool for demonstrating the threshold for cancer risk in refining the risk assessment as capably described by Dr. Klaunig. Hopefully, we can begin to increasingly use data-based decisions in risk assessment versus hypothetical low- dose extrapolations and mathematical modeling, building on the wealth of current understanding in human and rodent cancer processes in arenas beyond pharmaceutics. PMID- 11211993 TI - Response to "Epigenetic mechanisms of chemical carcinogenesis" by James E. Klaunig, Lisa M. Kamendulis, and Xu Yong. PMID- 11211994 TI - Response to "Epigenetic mechanisms of carcinogenesis" by Klaunig JE, Kamendulis LM and Xu Y. AB - It is now quite clear that carcinogenesis involves more than mutagenesis and an increased focus on epigenetic events underlying the transformation of a normal cell into a frank malignancy is appropriate. PMID- 11211995 TI - A true threshold dose in chemical carcinogenesis cannot be defined for a population, irrespective of the mode of action. AB - Strongly sigmoidal (S-shaped) dose-cancer incidence relationships are often observed in animal bioassays for carcinogenicity. If a genotoxic contribution is not plausible, an epigenetic mode of carcinogen action is proposed and a thresholded low dose-response suggested. In a strict sense, a threshold implies a no-yes situation, i.e., no effect up to the threshold dose and an effect above the threshold dose. A convincing explanation of the discontinuity of the gradient of the dose-response curve at the threshold dose is not available to me. However, the existence of a threshold is accepted for an individual. The threshold dose is the dose required for the manifestation of the tumor in an individual exactly at the end of a defined period of observation (for instance, 2 years in an animal bioassay, 75 years in humans). Because of genetic and lifestyle-dependent susceptibility differences, each animal or human has his individual threshold dose. For a group, no single threshold dose can be defined, irrespective of the mode of carcinogen action. Furthermore, in view of the stochastic elements in the process of carcinogenesis, the exact threshold dose can only be defined after tumor incidence and cannot be predicted. PMID- 11211996 TI - Response to Klaunig J.E. et al.'s "Epigenetic mechanisms of chemical carcinogenesis". PMID- 11211997 TI - The composition of cigarette smoke: a retrospective, with emphasis on polycyclic components. AB - The difficulties encountered in extrapolating biological activity from cigarette smoke composition provide generally applicable lessons as they are representative of the problems encountered with other complex mixtures. Researchers attempting to assess risk are faced with attempting to interpret data from a number of areas including: tobacco science; smoke/aerosol chemistry specific to tobacco; sophisticated analytical chemistry applications and techniques for trapping, collecting, separating, and quantifying very specific compounds at nanogram to picogram levels; numerous biological testing methodologies; and animal models of tumors and carcinogenesis. Numerous hypotheses have been developed over the past five decades and tested with the technology of the day in attempts to interpret the biological activity of cigarette smoke in relation to the chemistry of this complex mixture. These hypotheses fall into several categories discussed in this review: mechanisms of pyrogenesis of polycyclic aromatic hydrocarbons (PAHs) in tobacco smoke; levels of PAHs in cigarette mainstream smoke (MS) and its tumorigenicity in mouse skin-painting experiments; control of PAH levels in MS; chemical indicators of cigarette smoke condensate (CSC) tumorigenicity; control of levels of MS components partitioned between the vapor phase and particulate phase of MS; tumorigenic threshold limits of CSC and many of its components; tumorigenic aza-arenes in tobacco smoke; MS components reported to be ciliastatic to smokers' respiratory tract cilia; anticarcinogenic tobacco-smoke components. Of 52 hypotheses reviewed in this paper, 15 have excellent data supporting the hypothesis based on today's technology. The remaining 37 hypotheses, although originally plausible, have since become insupportable in light of new and contradictory data generated over the years. Such data were generated sometimes by the original authors of the hypotheses and sometimes by other investigators. The hypotheses presented today are less likely to be supplanted because they are well conceived and have a strong mechanistic basis. The challenge for the future is the generation and interpretation of data relating the chemistry and biological activity associated with the dynamic and complex mixture of tobacco smoke. PMID- 11211998 TI - Gas phase reactions of NH2Cl with anionic nucleophiles: nucleophilic substitution at neutral nitrogen. AB - Reactions of chloramine, NH2Cl, with HO-, RO- (R = CH3, CH3CH2, CH3CH2CH2, C6H5CH2, CF3CH2), F- , HS- , and Cl- have been studied in the gas phase using the selected ion flow tube technique. Nucleophilic substitution (S(N)2) at nitrogen to form Cl- has been observed for all the nucleophiles. The reactions are faster than the corresponding S(N)2 reactions of methyl chloride; the chloramine reactions take place at nearly every collision when the reaction is exothermic. The thermoneutral identity S(N)2 reaction of NH2Cl with Cl-, which occurs approximately once in every 100 collisions, is more than two orders of magnitude faster than the analogous reaction of CH3Cl. The significantly enhanced S(N)2 reactivity of NH2Cl is consistent with a previous theoretical prediction that the barrier height for the S(N)2 identity reaction at nitrogen is negative relative to the energy of the reactants, whereas this barrier height for reaction at carbon is positive. Competitive proton abstraction to form NHCl- has also been observed with more highly basic anions (HO-, CH3O-, and CH3CH2O-), and this is the major reaction channel for HO- and CH3O-. Acidity bracketing determines the heat of deprotonation of NH2Cl as 374.4 +/- 3.0 kcal mol(-1). PMID- 11211999 TI - Hydrogen bonds in gas-phase clusters between halide ions and olefins. AB - Gas-phase clustering reactions of halide ions (X- = F-, Cl-, Br-, and I-) with ethylene (C2H4) and propylene (C3H6) were studied with a pulsed electron beam mass spectrometer. Bonding energies of all cluster ions were found to be less than 10 kcal/mol, i.e., no anion-initiated polymerization of C2H4 and C3H6 took place. For the cluster F-(C2H4)n, a small gap in the binding energy is observed between n = 4 and 5 suggesting that the first shell is completed with n = 4. For larger halide ions, the bond energies for the clusters X-(C2H4)n were found to be nearly n independent. For Cl-(C3H6)n a steep decrease in binding energies was observed between n = 2 and 3 and n = 3 and 4. The structure of the cluster ions was investigated by ab initio calculations. X-(C2H4)n complexes were calculated to have hydrogen-bond geometries regardless of the identity of the halide ions, and bidentate (chelate) type geometries of X-(C3H6)1 were found. PMID- 11212000 TI - Ketalization of gaseous acylium ions. AB - A novel reaction of gaseous acylium ions: ketalization with diols and analogs, has been systematically studied via pentaquadrupole MS2 and MS3 experiments and ab initio calculations. A variety of alpha,beta-diols and their amino, thiol, ether, and thioether analogs have been tested for reactivity, mechanism evaluation, site selectivity, and for the effects of alpha- and beta interfunctional separation. As for condensed-phase ketalization of neutral carbonyl compounds followed by hydrolysis, gaseous acylium ions are chemically deactivated in the form of cyclic ionic ketals by ketalization, and are efficiently released via on-line collision-induced dissociation. Ketalization of acylium ions is shown to identify and structurally characterize alpha,beta-diols and their analogs, and to distinguish regioisomers. Diastereomers can also be distinguished, as illustrated for cis and trans 1,2-diaminocyclohexane. The MS2 and MS3 data together with 18O-labeling and ab initio calculations establish for acylium ion ketalization a mechanism of anchimeric assistance with participation of the neighboring acyl group. PMID- 11212001 TI - Characterization of the product ions from the collision-induced dissociation of argentinated peptides. AB - Tandem mass spectrometry performed on a pool of 18 oligopeptides shows that the product ion spectra of argentinated peptides, the [bn + OH + Ag]+ ions and the [yn - H + Ag]+ ions bearing identical sequences are virtually identical. These observations suggest strongly that these ions have identical structures in the gas phase. The structures of argentinated glycine, glycylglycine, and glycylglycylglycine were calculated using density functional theory (DFT) at the B3LYP/DZVP level of theory; they were independently confirmed using HF/LANL2DZ. For argentinated glycylglycylglycine, the most stable structure is one in which Ag+ is tetracoordinate and attached to the amino nitrogen and the three carbonyl oxygen atoms. Mechanisms are proposed for the fragmentation of this structure to the [b2 + OH + Ag]+ and the [Y2 - H + Ag]+ ions that are consistent with all experimental observations and known calculated structures and energetics. The structures of the [b2 - H + Ag]+ and the [a2 - H + Ag]+ ions of glycylglycylglycine were also calculated using DFT. These results confirm earlier suggestions that the [b2 - H + Ag]+ ion is an argentinated oxazolone and the [a2 H + Ag]+ an argentinated immonium ion. PMID- 11212002 TI - Electron transfer vs. proton transfer within radical-cation clusters of guanosine and deoxyguanosine with substituted naphthalenes and sinapinic acid. AB - Guanosine (G) and deoxyguanosine (dG) radical cations can be generated in the gas phase by single electron transfer (SET) within nucleoside-dimethoxynaphthalenes (1-2) electron-bound heterodimers produced by fast atom bombardment in a four sector mass spectrometer. The nucleobase guanine is much more easily oxidized when it is linked to a ribose moiety. The radical cation dimers formed by G and dG with sinapinic acid behave as proton-bound heterodimers. The experiments mimic to some extent the migration of radical sites within stacking bases which causes DNA damaging through depurination processes. PMID- 11212003 TI - Metastable decay of negatively charged oligodeoxynucleotides analyzed with ultraviolet matrix-assisted laser desorption/ionization post-source decay and deuterium exchange. AB - In an effort to understand the initiating step in metastable-ion decay of UV matrix-assisted laser desorption/ionization (MALDI)-produced ions, we conducted experiments in which we exchanged all active protons for deuterons of tetrameric and hexameric oligodeoxynucleotides. We wish to address the controversial proposal that in the negative-ion mode, as in the positive-ion mode, fragmentation is driven by nucleobase protonation. The results show unambiguously that proton transfer, leading to zwitterion formation, charges a nucleobase prior to its elimination. The zwitterion formation directs fragmentation of both positive and negative oligodeoxynucleotide ions. Poly-T-rich oligodeoxynucleotide tetramers show surprising differences in the negative compared to the positive ion mode, as thymine is preferentially expelled, instead of a nucleobase with higher proton affinity. For the exceptional case of negatively charged poly-T rich oligodeoxynucleotide tetramers generated by MALDI, we propose that zwitterion formation with positive charging of a nucleobase leads to base stabilization in the negative-ion mode through an interaction of the positive nucleobase with the excess negative charge. Moreover, backbone cleavages (accompanied by H rearrangement) of a phosophodiester bond give first-generation products that can be traced back to this tripolar complex bearing one positive and two negative charges, all of which may be interacting. PMID- 11212004 TI - Fragmentation mechanisms of oligodeoxynucleotides studied by H/D exchange and electrospray ionization tandem mass spectrometry. AB - We used solution-phase hydrogen/deuterium (H/D) exchange and multistage tandem mass spectrometry (MS/MS) experiments in an electrospray ion-trap mass spectrometer operating in the negative-ion mode to investigate the consequences of the loss of a high proton-affinity (PA) base from T-rich tetra and hexadeoxynucleotides. The T-rich oligodeoxynucleotides containing one or two other nucleobases take advantage of the mass spectral inertness of T because fragmentation of a T-rich oligomer is simple, allowing a tight focus on those processes of interest. Furthermore, determination of T-rich oligodeoxynucleotides may be a starting point in the development of a mass spectrometric scheme to understand the mutagenicity of various types of DNA damage by UV radiation. For nine oligodeoxynucleotides, the nucleobases were charged by nearly exclusive D transfer and then expelled as neutral bases. Loss of the base located at the 3' end is preferred over that from the 5' terminus when the two bases are identical. The observation of partially exchanged fragments from a completely exchanged precursor ion proves intramolecular H/D exchange between hydrogen atoms that can exchange in water and those that cannot. The multiplicity of the product-ion peaks provides information on decomposition pathways and origins of the product ions and shows that the loss of base is the first step in all fragmentation of hexanucleotides, but is a competitive process for tetranucleotide fragmentation. PMID- 11212005 TI - A mechanistic study of electrospray mass spectrometry: charge gradients within electrospray droplets and their influence on ion response. AB - A model has been developed to account qualitatively for the effects of ion pairing, surface activity, and electrophoretic mobility in electrospray mass spectrometry. The model is tested with various salt and amino acid mixtures. The data suggest that the axial charge gradient arising from electrophoretic separation at droplet genesis may persist within the electrosprayed droplets at least until the first droplet fission, accounting for the field dependence of detected ion clustering of quaternary ammonium salts and for the relatively field invariant charge distribution of horse heart myoglobin samples. PMID- 11212006 TI - Protein identification by in-gel digestion, high-performance liquid chromatography, and mass spectrometry: peptide analysis by complementary ionization techniques. AB - A biologically active protein fraction was isolated from rabbit intestine, purified by one-dimensional SDS-PAGE and stained with Coomassie Brilliant Blue. A predominant band of approximately 110-130 kDa was excised and digested in-gel with trypsin. The resulting peptides were extracted then separated by microbore reversed-phase high-performance liquid chromatography (HPLC). Mass spectrometric data from one HPLC fraction obtained by two different ionization techniques proved to be complementary. Matrix-assisted laser desorption/ionization (MALDI) showed nine peptide masses, which by post source decay analysis and database searching were attributed to two proteins. Nanoflow electrospray analysis performed on a hybrid tandem mass spectrometer of quadrupole-quadrupole orthogonal acceleration time-of-flight (QqTOF) geometry detected six additional peptide components. On the basis of the additional peptides and superior quality collision-induced dissociation spectra typical of this instrument type, two further proteins were identified. The resolution afforded by the QqTOF instrument permitted charge state determination for the fragment ions while preserving the high detection sensitivity that was essential in obtaining the composition of this mixture of proteins. PMID- 11212008 TI - Similarity between condensed phase and gas phase chemistry: fragmentation of peptides containing oxidized cysteine residues and its implications for proteomics. AB - Amino acid residues containing thioethers are easily oxidized during protein purification, derivatization, and/or digestion. For instance, oxidation of methionine residues in proteins during SDS-PAGE is commonly observed. Under low energy collision induced dissociation this gives rise to a second series of fragment ion of lower abundance that are shifted by -64 Da when compared to the oxidized methionine-containing fragments. We report here that alkylated cysteine residues can be found in their oxidized form too, indicating that the oxidation of thioethers can occur during and following protein digestion and not only during SDS-PAGE or reduction and alkylation. Collision induced dissociation experiments on the singly- and multiply-charged species reveals that these peptides preferentially undergo elimination reactions that forms a dehydroalanine from the oxidized, alkylated cysteine residue. This contrasts to the less abundant elimination reaction of peptides containing oxidized methionines which cannot form an alpha,beta-unsaturated compound, but parallels the condensed phased chemistry of sulfoxides. The masses of both precursor and product ions are shifted such that these peptides cannot be identified in database searches with current algorithms. Incorporation of this fragmentation pattern is important for the isotope-coded affinity tag approach since this method is based on peptides containing cysteine residues. PMID- 11212007 TI - A new crosslinker for mass spectrometric analysis of the quaternary structure of protein complexes. AB - Mass spectrometric structural analysis of crosslinked peptides is a powerful method to elucidate the spatial arrangement of polypeptides in protein complexes. Our aim is to develop bifunctional crosslinkers that, after crosslinking protein complexes followed by proteolytic digestion, give rise to crosslinked peptides that can be readily tracked down by mass spectrometry. To this end we synthesized the crosslinker N-benzyliminodiacetoyloxysuccinimid (BID), which yields stable benzyl cation marker ions upon low-energy collision-induced dissociation (CID) tandem mass spectrometry. Sensitive detection of the marker ion upon low-energy CID is demonstrated with different BID-crosslinked peptide preparations. With BID it becomes possible to retrieve crosslinked and crosslinker-adducted peptides, without the necessity of purifying crosslinked peptides prior to identification. The basic design of this crosslinker can be varied upon, in order to meet specific crosslinking needs. PMID- 11212009 TI - Nonneurologic hand pain versus carpal tunnel syndrome: do psychological measures differentiate? AB - OBJECTIVE: To determine whether psychological measures would differentiate a group of patients with physician-diagnosed nonneurologic hand pain from patients with carpal tunnel syndrome (CTS). Many patients, who also displayed symptoms of psychological distress, were referred to an electrodiagnostic clinic with a diagnosis of possible CTS; they subsequently had normal nerve conduction studies. DESIGN: Sixty patients with hand pain were referred to either of two university clinics for electrophysiologic testing, were assigned to either the CTS or nonneurologic group, and were compared on a series of psychometric tests. RESULTS: The Beck Depression Inventory and McGill Pain Questionnaire showed that the physician-assigned nonneurologic patients have a greater degree of depression, use more affective adjectives, and choose more words on the McGill Pain Questionnaire than the physician-assigned CTS group. The nonneurologic group also scored higher on indices of self-reported disability on the Pain Disability Inventory in five of seven categories. Although the CTS group perceived more control over their pain, no differences were observed in the types of coping strategies used on the Coping Strategy Questionnaire. Finally, the nonneurologic group had more Workers' Compensation Board claims. CONCLUSION: Evidence of important psychological issues in some patients with hand pain suggests a need for greater awareness among treating physicians. PMID- 11212010 TI - Compound nerve action potential of common peroneal nerve recorded at fibular neck: its clinical usefulness. AB - OBJECTIVE: To determine the clinical usefulness of the compound nerve action potential of the common peroneal nerve recorded immediately distal to or at the fibular neck, at the same time stimulating the common peroneal nerve laterally at the posterior knee. DESIGN: For recording the compound nerve action potential of the common peroneal nerve, the active recording electrode was secured just distal to or at the fibular neck area, whereas the stimulating electrode was placed on the medial border of the lateral hamstring tendon at the level of the popliteal crease. To reduce shock artifacts, a biphasic stimulation was used. RESULTS: In 35 adults (n = 19 men), 70 nerves were tested. The compound nerve action potential from each individual was recorded. The compound nerve action potential amplitude of a baseline-to-negative peak and conduction velocity were measured on both sides. For comparisons of the side-to-side amplitude and conduction velocity, Wilcoxon's signed-rank test was applied. CONCLUSION: This approach of recording the compound nerve action potential of the common peroneal nerve, in addition to conventional methods, may enhance the process of determining the precise localization of peroneal nerve lesion in the knee. PMID- 11212011 TI - Factor analysis of quality of life, dyspnea, and physiologic variables in patients with chronic obstructive pulmonary disease before and after rehabilitation. AB - OBJECTIVE: To identify the relationships between quality of life (QOL) and the clinical state using factor analysis pre- and postrehabilitation. Patients with chronic obstructive pulmonary disease (COPD) suffer from a significant physiologic impairment associated with an altered QOL. Comprehensive rehabilitative programs, including exercise training, have beneficial effects on exercise tolerance and QOL for these patients. DESIGN: Factor analysis (n = 6) was conducted using the data of 32 patients with COPD. Patients had been evaluated for QOL using the Nottingham Health Profile (NHP), spirometric values, dyspnea, and the variables assessed by an incremental exercise test at three levels of activity. All measurements were obtained pre- and postrehabilitation. RESULTS: Factor analysis showed that the following two factors characterize the pathophysiologic condition of patients with COPD: (1) the specific cardiorespiratory responses to incremental exercise test and the spirometric values; and (2) the QOL results. The factor analysis results differed with the testing time (pre, post) and the level of activity. CONCLUSIONS: QOL, as evaluated by a generic questionnaire and the clinical state of patients with COPD, was independent; this independence characterized the pathophysiologic condition of our patients. Our results reinforce the usefulness of different types of evaluation, especially pre- and postrehabilitation, because they reflect independent benefits used to understand the success and follow-up of rehabilitative programs. PMID- 11212012 TI - Influence of admission functional status on functional change after stroke rehabilitation. AB - OBJECTIVE: To determine whether the admission functional score influences the functional change after stroke rehabilitation. DESIGN: Two hundred forty-three patients who had received the Functional Independence Measure (FIM) assessment at admission and at discharge were enrolled in the study. The patients were stratified into three groups according to their FIM total scores at admission, i.e., < or =36, 37 to 72, and > or =73. RESULTS: The Scheffe's multiple comparison test showed that patients with FIM total scores of > or =73 at admission were significantly younger (58 +/- 11 [SD] yr) than those who had scores of 37 to 72 (64 +/- 11 yr) or < or =36 (66 +/- 12 yr). Patients with FIM total scores of 37 to 72 at admission showed significantly higher FIM gain (37 +/ 15) compared with those patients who had scores of > or =73 (20 +/- 10) or < or =36 (29 +/- 23). CONCLUSION: The functional levels of affected patients at admission stratified by the FIM scale roughly predict the degree of functional gain after rehabilitation in survivors with a first episode of ischemic stroke. Moderately affected patients will benefit from intensive rehabilitation. These findings may be useful for rehabilitation triage. PMID- 11212013 TI - Paravertebral venous plexus distention (Batson's): an inciting etiologic agent in lumbar radiculopathy as observed by venous angiography. AB - Can the paravertebral plexus of veins adjacent to the spinal nerve root within the narrow confines of the lateral neural canal be a collateral generator of radicular pain when no other evidence of spinal pathology is evident? A patient with complaints of intractable lumbar radiculopathy and an otherwise unremarkable clinical neuromusculoskeletal examination, as well as normal imaging and electrodiagnostic studies, is reviewed with special reference to symptomatic and paravertebral venous responses to both a Valsalva maneuver and dipyridamole infusion as imaged by magnetic venous angiography. PMID- 11212014 TI - Do endplate noise and spikes arise from normal motor endplates? AB - The concept that the endplate noise and endplate spike components of motor endplate potentials represent normal endplate potentials seems to be flawed. The morphology of the normal miniature endplate potentials described in the physiology literature is different from the morphology of the noise-like component of endplate potentials. This noise-like component is identified as normal in current electromyographic literature. There is strong experimental evidence that one source of the endplate noise component is grossly increased release (up to three orders of magnitude) of acetylcholine from the nerve terminal of that neuromuscular junction. The spikes can be accounted for by release of additional acetylcholine in response to mechanical stimulation by the electromyographic needle. Other possibilities exist. PMID- 11212015 TI - Measures of central tendency in rehabilitation research: what do they mean? AB - Measures of central tendency including the mean, median, and mode are commonly reported in rehabilitation research. It is believed that the relationship among the mean, median, and mode changes in a specific way when the distribution being analyzed is skewed. A number of widely used textbooks were reviewed to determine how the relationship among the mean, median, and mode is presented in the health sciences and rehabilitation literature. We report a potential misinterpretation of the relationship between measures of central tendency that was identified in several research and statistical textbooks on the subject of rehabilitation. The misinterpretation involves measures of central tendency derived from skewed unimodal sample distributions. The reviewed textbooks state or imply that in asymmetrical distributions, the median is always located between the mode and mean. An example is presented illustrating the fallacy of this assumption. The mean and median will always be to the right of the mode in a positively skewed unimodal distribution and to the left of the mode in a negatively skewed distribution; the order of the mean and median is impossible to predict or generalize. The assumption that the median always falls between the mode and mean in the calculation of coefficients of skewness has implications for the interpretation of exploratory and confirmatory data analysis in rehabilitation research. PMID- 11212016 TI - Defining the population, treatments, and outcomes of interest: reconciling the rules of biology with meaningfulness. AB - Population characteristics, treatment needs, therapeutic interventions, and outcomes are inextricably linked. To appreciate the treatment needs and outcomes of populations served by rehabilitation medicine, it is essential to understand how specific conditions impair mental and physical functioning, given the environments within which people choose to live. States of the mind and body combine with the characteristics of the man-made and natural world and the social infrastructure to yield disabilities and, thus, shape the demand for rehabilitation services. The 1997 draft of ICIDH-2: International Classification of Impairments, Activities, and Participation (ICIDH-2) is described as an approach to population definition and outcome assessment. A new and evolving model referred to as the spheres of human-environmental integration (HEI) is applied to expressing the nonlinear and overlapping relationships among the ICIDH 2 dimensions. HEI is defined as the individual's potential for meaningful physical and mental activity as determined by physical and mental capabilities in relationship to the man-made and natural worlds, social expectations, and available resources. HEI can be expanded by reducing disabilities through medical and rehabilitation interventions and by eliminating environmental barriers. This dual approach implies a need to integrate rehabilitation sciences with the principles of independent living, which view disablement as a function of the environment. The ICIDH-2 dimensions combined with HEI are used to define populations and to study the mechanisms and effects of alternative treatments through various techniques of case-mix measurement, disability staging, and utility assessment. PMID- 11212017 TI - Identification of cervical radiculopathies: optimizing the electromyographic screen. AB - OBJECTIVE: To determine the optimal electromyography screening examination of the upper limb that ensures detection of those cervical radiculopathies, which can be electrodiagnostically confirmed, yet minimizes the number of muscles studied. DESIGN: A prospective multicenter study was conducted from May 1996 to September 1997 at five institutions. Patients who were referred to participating electrodiagnostic laboratories with suspected cervical radiculopathy were recruited. A standard set of muscles were examined by needle electromyography. Patients with electrodiagnostically confirmed cervical radiculopathies, based on electromyography findings, were selected for analysis. Muscle screens were tested against this group to determine whether the screen identified the patients with radiculopathy. RESULTS: There were 101 patients with cervical radiculopathies representing all cervical root levels. When paraspinal muscles were one of the screening muscles, five muscle screens identified 90% to 98% of radiculopathies, six muscle screens identified 94% to 99%, and seven muscle screens identified 96% to 100%. When paraspinal muscles were not part of the screen, eight distal limb muscles recognized 92% to 95% of radiculopathies. CONCLUSION: This study demonstrated that six muscle screens including paraspinal muscles yielded consistently high identification rates. Studying additional muscles led to marginal increases in identification. PMID- 11212018 TI - Outcomes of cardiopulmonary arrest in an acute rehabilitation setting. AB - OBJECTIVE: Fifty consecutive cases of cardiopulmonary arrest with administration of cardiopulmonary resuscitation (CPR) during a 6-yr period at a freestanding academic acute rehabilitation hospital were identified. DESIGN: Medical records of 49 patients were available for review. Outcomes of survival of arrest, survival to 24 hr postarrest, survival to discharge from the hospital were determined, and chi2 or Fisher's exact tests were performed to investigate relationships between survival and admission functional status, age, gender, and medical comorbidities. RESULTS: Forty-three percent of patients survived the initial arrest, 37% survived to 24 hr post-CPR, and 18% survived to hospital discharge. We were unable to identify any statistically significant predictors of survival post-CPR. Six of the nine survivors returned to the acute rehabilitation setting after cardiopulmonary arrest, and five of these patients made significant functional gains. CONCLUSIONS: Outcomes after CPR in patients undergoing acute rehabilitation in one setting were not significantly different from those reported for patients in other healthcare settings. These data may be used by healthcare professionals to enhance discussions concerning advance healthcare planning (including resuscitation plans) with patients and families. Larger studies are needed to clarify the prognostic role of prior functional status in predicting CPR outcomes, particularly in the context of various diagnostic categories and age groups. PMID- 11212019 TI - In vitro pharmacologic effect of two endothelin-1 antagonists on equine colonic arteries and veins. AB - OBJECTIVE: To evaluate the effectiveness of 2 potential endothelin (ET)-1 antagonists in blocking the contractile responses of equine colonic vessels to increasing concentrations of ET-1. SAMPLE POPULATION: Mesenteric vessels from 6 clinically healthy horses. PROCEDURE: Colonic vessels (arterial and venous rings) were placed in organ baths with oxygenated Tyrode solution at 37 C. Each was attached to a force transducer interfaced with a polygraph, and 2 g of tension was applied and equilibrated for 45 minutes. Then, B-1 (PD 142893) and B-2 (PD 145065) ET-1 antagonists were tested. One ring from each vessel type was used as a control for determining concentration-response relationships of ET-1 (10(-10) to 10(-6)M). Three rings of each vessel type were incubated with 3 concentrations of each antagonist (10(-7), 10(-6), and 10(-5) M) for 30 minutes before ET induced contractions were determined. The maximum contractile response and pA2 values were determined. RESULTS: Vessels contracted in a concentration-dependent manner to ET-1. Arteries responded slowly but reached greater contractions. Veins responded immediately with sustained contractions. Both antagonists inhibited contractions in a concentration-dependent manner with significant differences at 10(-6) and 10(-5)M for arteries and 10(-5) M for veins. Complete blockade of contractions was observed with B-2 (10(-5)M). The pA2 values for B-1 were 8.26 and 6.82 for arteries and veins, respectively, whereas they were 8.25 and 7.21 for B-2. CONCLUSION AND CLINICAL RELEVANCE: Both antagonists effectively blocked ET-1-induced contractions of equine colonic vessels. Because B-2 is water soluble and caused complete blockade at 10(-5) M, it appears to be the preferred antagonist. PMID- 11212020 TI - Effects of enrofloxacin and magnesium deficiency on matrix metabolism in equine articular cartilage. AB - OBJECTIVE: To investigate the effects of enrofloxacin and magnesium deficiency on explants of equine articular cartilage. SAMPLE POPULATION: Articular cartilage explants and cultured chondrocytes obtained from adult and neonatal horses. PROCEDURE: Full-thickness explants and cultured chondrocytes were incubated in complete or magnesium-deficient media containing enrofloxacin at concentrations of 0, 1, 5, 25, 100, and 500 microg/ml. Incorporation and release of sulfate 35S over 24 hours were used to assess glycosaminoglycan (GAG) synthesis and degradation. An assay that measured binding of dimethylmethylene blue dye was used to compare total GAG content between groups. Northern blots of RNA from cultured chondrocytes were probed with equine cDNA of aggrecan, type-II collagen, biglycan, decorin, link protein, matrix metalloproteinases 1, 3, and 13, and tissue inhibitor of metalloproteinase 1. RESULTS: A dose-dependent suppression of 35S incorporation was observed. In cartilage of neonates, 35S incorporation was substantially decreased at enrofloxacin concentrations of 25 mg/ml. In cartilage of adult horses, 35S incorporation was decreased only at enrofloxacin concentrations of > or =100 microg/ml. Magnesium deficiency caused suppression of 35S incorporation. Enrofloxacin or magnesium deficiency did not affect GAG degradation or endogenous GAG content. Specific effects of enrofloxacin on steady state mRNA for the various genes were not observed. CONCLUSION AND CLINICAL RELEVANCE: Enrofloxacin may have a detrimental effect on cartilage metabolism in horses, especially in neonates. PMID- 11212021 TI - Results of cystometry and urethral pressure profilometry in dogs sedated with medetomidine or xylazine. AB - OBJECTIVE: To compare effects of medetomidine and xylazine hydrochloride on results of cystometry and micturition reflexes in healthy dogs and results of urethral pressure profilometry (UPP) in sedated and conscious dogs. ANIMALS: 20 dogs. PROCEDURES: Urodynamic testing was performed 6 times in each dog (3 times after administration of xylazine [1 mg/kg of body weight, IV] and 3 times after administration of medetomidine (30 microg/kg, IM). Before each episode of sedation, UPP was performed. Heart and respiratory rates and indirect blood pressures were recorded prior to and 5, 10, 20, and 30 minutes after injection of sedative. Cystometry measurements included threshold volume, threshold pressure, and tonus limb. The UPP measurements included maximal urethral closure pressure (MUCP), functional profile length, and, in male dogs, plateau pressure. RESULTS: Mean MUCP was decreased markedly in xylazine- and medetomidine-sedated dogs. Xylazine and medetomidine also decreased plateau pressure in male dogs. The MUCP measurements were consistent among days for conscious and xylazine-sedated dogs but were inconsistent for medetomidine-sedated female dogs. The proportion of valid cystometry measurements was greater for xylazine (39 of 60) than for medetomidine (27 of 60). Cystometry was considered invalid when bladder pressure reached 30 cm H2O without initiation of a micturition reflex. CONCLUSIONS AND CLINICAL RELEVANCE: Medetomidine and xylazine have similar effects on measurement of UPP and cystometry. Medetomidine was less consistent among days for UPP in female dogs and produced fewer valid cystometry tests, compared with xylazine. For urodynamic evaluations, medetomidine administered IM cannot be substituted for xylazine administered IV. PMID- 11212022 TI - Comparison of number of Streptococcus uberis calculated on a volume or weight basis in sand and sawdust bedding. AB - OBJECTIVE: To determine a method for comparing counts of Streptococcus uberis in sand and sawdust and account for the influence of weight or volume of the bedding material. SAMPLE POPULATION: 2 sources of kiln-dried sawdust and 2 sources of washed sand. PROCEDURES: Sterilized bedding material (100 ml) was weighed and uniformly distributed in an aluminum pan. Each sterilized bedding material was inoculated with a mean of 3.6 X 10(6) (experiment 1) or 2.4 X 10(7) (experiment 2) colony-forming units (CFU) of S uberis/ml of bedding material. Without allowing time for replication of S uberis, inoculated bedding materials were washed with sterile saline (0.9% NaCl) solution. A 200-ml aliquot of wash solution was serially diluted up to 2,500 times with additional saline solution and inoculated on plates containing tryptose agar with 5% sheep blood. After incubation for 48 hours, number of CFU of S uberis was counted. This procedure was replicated 19 and 16 times for each bedding material in experiments 1 and 2, respectively. RESULTS: Evaluation of Bonferroni 95% confidence intervals revealed significant differences for counts of S uberis calculated on a weight basis between sand and sawdust. CONCLUSIONS AND CLINICAL RELEVANCE: Comparison of counts of S uberis determined on a volume basis for sand and sawdust accentuates to a lesser degree the weight difference of the bedding materials and ensures a more appropriate comparison of number of S uberis. PMID- 11212023 TI - Prevalence of Streptococcus iniae in tilapia, hybrid striped bass, and channel catfish on commercial fish farms in the United States. AB - OBJECTIVE: To determine the prevalence of Streptococcus iniae in tilapia (Oreochromis spp), hybrid striped bass (Morone chrysops X M saxatilis), and channel catfish (Ictalurus punctatus) on commercial fish farms in the United States. ANIMALS: 1,543 fish (970 tilapia, 415 hybrid striped bass, and 158 channel catfish). PROCEDURES: The dry-swab technique was used for collection of specimens for streptococcal isolation. Specimens were shipped by overnight delivery and processed by use of standard bacteriologic techniques. RESULTS: Streptococcus iniae was not isolated from market-size channel catfish. Prevalence in tilapia and hybrid striped bass was 37 of 970 (3.81%) and 30 of 415 (7.23%), respectively. Prevalence by farm ranged from 0.0 to 27.4% for tilapia and 0.0 to 21.6% for hybrid striped bass. In tilapia, prevalence was lowest in market-size and nursery fish (4 of 239 [1.67%] and 3 of 339 [0.88%], respectively), with an increase in prevalence for fish in the grow-out stage (30 of 337 [7.96%]). For hybrid striped bass, prevalence was lowest in nursery and market-size fish (3 of 96 [3.12%] and 1 of 47 [2.12%], respectively) and highest in fish in the grow-out stage (26 of 272 [9.56%]). Prevalence in market-size tilapia and hybrid striped bass was 5 of 286 (1.75%). CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study do not support the contention that S iniae is a serious public health threat associated with commercially raised fish; rather, it represents a limited risk for older or immunocompromised people who incur puncture wounds while handling and preparing fish. PMID- 11212024 TI - Electroacupuncture-induced neural activation detected by use of manganese enhanced functional magnetic resonance imaging in rabbits. AB - OBJECTIVE: To investigate the effects of acupuncture on neural activity detected by use of manganese-enhanced functional magnetic resonance imaging (fMRI) and elucidate the relationship between somatic acupoint stimulation and brain activation. ANIMALS: 40 New Zealand White rabbits. PROCEDURE: Manganese-enhanced fMRI was performed in anesthetized rabbits manipulated with electroacupuncture (EA) on Zusanli (ST-36) and Yanglingquan (GB-34) acupoints. Image acquisition was performed on a 1.5T superconductive clinical scanner with a circular polarized extremity coil. T1-weighted images were acquired sequentially as follows: baseline, after mannitol injection, after manganese infusion, and 5 and 20 minutes after initiation of EA. RESULTS: Changes in focal neural activity were detected by use of manganese-enhanced fMRI. Stimulation on Zusanli (ST-36) for 5 minutes resulted in activation of the hippocampus, whereas stimulation on Yanglingquan (GB-34) resulted in activation of the hypothalamus, insula, and motor cortex. Activation became less specific after 20 minutes of EA. Furthermore, stimulation on ipsilateral acupoints led to bilateral brain activation. CONCLUSIONS AND CLINICAL RELEVANCE: Each acupoint has a corresponding cerebral linkage, and stimulation on these points resulted in time-dependent neural activation. Understanding the linkage between peripheral acupoint stimulation and central neural pathways may provide a useful guide for clinical applications of acupuncture. PMID- 11212025 TI - Pharmacokinetics and adverse effects of butorphanol administered by single intravenous injection or continuous intravenous infusion in horses. AB - OBJECTIVE: To determine an infusion rate of butorphanol tartrate in horses that would maintain therapeutic plasma drug concentrations while minimizing development of adverse behavioral and gastrointestinal tract effects. ANIMALS: 10 healthy adult horses. PROCEDURE: Plasma butorphanol concentrations were determined by use of high-performance liquid chromatography following administration of butorphanol by single IV injection (0.1 to 0.13 mg/kg of body weight) or continuous IV infusion (loading dose, 17.8 microg/kg; infusion dosage, 23.7 microg/kg/h for 24 hours). Pharmacokinetic variables were calculated, and changes in physical examination data, gastrointestinal tract transit time, and behavior were determined over time. RESULTS: A single IV injection of butorphanol was associated with adverse behavioral and gastrointestinal tract effects including ataxia, decreased borborygmi, and decreased defecation. Elimination half-life of butorphanol was brief (44.37 minutes). Adverse gastrointestinal tract effects were less apparent during continuous 24-hour infusion of butorphanol at a dosage that resulted in a mean plasma concentration of 29 ng/ml, compared with effects after a single IV injection. No adverse behavioral effects were observed during or after continuous infusion. CONCLUSIONS AND CLINICAL RELEVANCE: Continuous IV infusion of butorphanol for 24 hours maintained plasma butorphanol concentrations within a range associated with analgesia. Adverse behavioral and gastrointestinal tract effects were minimized during infusion, compared with a single injection of butorphanol. Continuous infusion of butorphanol may be a useful treatment to induce analgesia in horses. PMID- 11212026 TI - Epidemiologic features of Campylobacter jejuni isolated from poultry broiler houses and surrounding environments as determined by use of molecular strain typing. AB - OBJECTIVE: To genetically type Campylobacter jejuni isolates from broiler houses or the external environment to identify the source of Campylobacter organisms in broiler chickens. SAMPLE POPULATION: Environmental samples associated with broiler chickens, in commercial grow-out houses. PROCEDURE: Polymerase chain reaction (PCR) was used to amplify flaB, and the amplicon was digested with Sau3A to create a restriction fragment length polymorphism assay; PCR was also used to detect a transcribed spacer region in the 23S rRNA gene. RESULTS: Isolates possessing a 23S spacer region were more prevalent outside broiler houses than inside. Houses that had previously contained chickens or lacked biosecurity procedures were more likely to contain isolates possessing the 23S spacer. One house contained only isolates possessing the spacer, whereas an adjacent house contained only isolates lacking the spacer. The flaB type detected in broiler houses was different from the type detected in the environment; however, many isolates within the broiler houses contained untypable flaB genotypes. CONCLUSIONS AND CLINICAL RELEVANCE: Most isolates from within houses were genetically distinct from isolates from outside houses that were examined by bacteriologic culture, suggesting an undetected source of C jejuni. Detection of isolates containing the 23S spacer appeared to be an indicator of environmental contamination of the houses. The observation of completely different C jejuni genetic types simultaneously within adjacent houses suggests that some types do not compete successfully during the grow-out period. In addition, the diversity of genotypes identified within broiler houses indicates the complexity of the ecologic features of C jejuni in the chicken environment. PMID- 11212027 TI - Evaluation of glycoprotein Ib expression on feline platelets. AB - OBJECTIVE: To determine whether platelets obtained from cats expressed glycoprotein Ib (GPIb). SAMPLE POPULATION: Platelets obtained from 11 specific pathogen-free cats. PROCEDURE: Platelets were analyzed by use of immunofluorescence microscopy, flow cytometry, sodium dodecyl sulfate polyacrylamide gel electrophoresis, western immunoblot analysis, and immunoprecipitation. RESULTS: Immunofluorescence microscopy and flow cytometry revealed the protein on the surface of feline platelets. Biochemical studies (western immunoblot analysis and immunoprecipitation) revealed a 140-kd membrane glycoprotein. Additional biochemical studies revealed that feline GPIb was sensitive to proteolysis, because platelet cytoskeletons prepared with low concentrations of a calpain inhibitor (ie, leupeptin; 100 microg/ml) had substantial proteolysis, and there was an association of protein fragments with the actin cytoskeleton. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of these results indicate that feline platelets express a 140-kd membrane protein that is recognized by monoclonal antibodies developed against GPIb. Application of standardized ELISA to quantitate glycocalicin, the water-soluble fragment of GPIb, may provide important information on the production of microvesicles, increased platelet turnover, and abnormal proteolysis. PMID- 11212028 TI - Evaluation of effectiveness of a vaccination program against an infectious disease at the population level. AB - OBJECTIVE: To evaluate the application of a vaccine in a population of animals. SAMPLE POPULATION: Field-trial data from the literature. PROCEDURE: A spreadsheet simulation model was constructed to estimate the impact of a vaccination program, assuming various population sizes, transmission rates, and vaccine efficacies. RESULTS: Total effectiveness (proportion of affected animals [ie, cases] avoided) increased with the vaccinated proportion of the population. However, with a highly efficacious vaccine, this relationship discontinued after a sufficient vaccination proportion was reached, reflecting herd immunity. Evaluation of a case study indicated that what may be considered a poor vaccine on the basis of its low efficacy may protect a substantial portion of the population if the vaccine is administered to a sufficient number of susceptible animals. Further investigation of a case study of horses indicated that evaluating a vaccine based solely on its efficacy could greatly underestimate its value. CONCLUSIONS AND CLINICAL RELEVANCE: When evaluating a vaccine applied to a population, in addition to the vaccine efficacy, the vaccination rate, cost of the vaccine, potential disease transmission rate, and number and cost of cases avoided must also be considered. Efficacy may underestimate vaccine value in terms of the reduction of indirect cases typically avoided when vaccination is applied in a population. PMID- 11212029 TI - Locomotor characteristics of horses with navicular disease. AB - OBJECTIVE: To determine whether force-plate evaluation of horses with navicular disease would reveal an abnormal gait that persists despite loss of sensation to the palmar foot region, which may predispose such horses to navicular disease. ANIMALS: 17 clinically normal Thoroughbreds and 8 Thoroughbreds with navicular disease. PROCEDURE: Data on ground reaction forces were obtained in trotting horses, using a force plate. Force-time curve variables for clinically normal horses were derived from 4 points at the beginning and 4 points at the end of the vertical and craniocaudal horizontal plots. Principal component analysis was undertaken separately on beginning-of-stride and end-of-stride data, and the first 2 components were represented graphically. Rotation matrices were applied to equivalent data for horses with navicular disease before and after disruption of sensation by administration of a palmar digital nerve blockade. RESULTS: Prior to nerve block, horses with navicular disease differed significantly from normal horses for beginning-of-stance phase and end-of-stance phase variables. After nerve block, horses with navicular disease maintained the same significant differences from clinically normal horses only for variables at the beginning-of stance phase. CONCLUSIONS AND CLINICAL RELEVANCE: Horses with navicular disease have abnormal limb-loading force patterns that are not altered by loss of sensation in the palmar region. These abnormal patterns were detected in a horse without navicular disease. Some horses are predisposed to navicular disease as a result of an inherent abnormal gait pattern. Analysis of gait patterns could be used for detection and appropriate management of horses susceptible to development of navicular disease. PMID- 11212030 TI - Quantitative assessment of mast cells and expression of IgE protein and mRNA for IgE and interleukin 4 in the gastrointestinal tract of healthy dogs and dogs with inflammatory bowel disease. AB - OBJECTIVE: To characterize the mucosal IgE network in dogs affected with inflammatory bowel disease (IBD) and compare it with that for healthy dogs. ANIMALS: 9 healthy dogs and 20 dogs with IBD. PROCEDURE: In situ hybridization of mRNA specific for IgE and interleukin 4 (IL-4) and immunohistochemical analysis for IgE protein and 2 markers of mast cells (ie, tryptase and chymase) were performed on tissue sections obtained from the gastrointestinal (GI) tract and lymph nodes of dogs. RESULTS: Dogs with IBD had significantly more cells positive for IgE protein and more mast cells in the GI mucosa than healthy dogs. Despite this significant increase in number of cells positive for IgE, cells positive for IgE mRNA were rarely detected in the GI mucosa; most cells positive for IgE mRNA were found in mesenteric lymph nodes. Signal pattern of IL-4 mRNA was similar to that of IgE mRNA. CONCLUSIONS AND CLINICAL RELEVANCE: The increased numbers of cells positive for IgE and mast cells in dogs with IBD suggest hypersensitivity such as hypersensitivity to bacterial or dietary-derived antigens in the intestinal lumen. Future studies need to elucidate whether this represents a cause of inflammation or is a result of the inflammatory process of IBD. PMID- 11212031 TI - Partial characterization of retroviruses from boid snakes with inclusion body disease. AB - OBJECTIVE: To characterize retroviruses isolated from boid snakes with inclusion body disease (IBD). ANIMALS: 2 boa constrictors with IBD and 1 boa exposed to an affected snake. PROCEDURE: Snakes were euthanatized, and tissue specimens and blood samples were submitted for virus isolation. Tissue specimens were cultured with or without commercially available viper heart cells and examined by use of transmission electron microscopy (TEM) for evidence of viral replication. Reverse transcriptase activ ty was determined in sucrose gradient-purified virus. Western blotting was performed, using polyclonal antibodies against 1 of the isolated viruses. Specificity of the rabbit anti-virus antibody was evaluated, using an immunogold-labeling TEM technique. RESULTS: 3 viruses (RV-1, RV-2, and RV-3) were isolated. The isolates were morphologically comparable to members of the Retroviridae family. Reverse transcriptase activity was high in sucrose gradient fractions that were rich in virus. Polyclonal antibody against RV-1 reacted with proteins of similar relative mobility in RV-1 and RV-2. By use of immunogold labeling, this antibody also recognized virions of both RV-1 and RV-2. CONCLUSIONS AND CLINICAL RELEVANCE: A retrovirus was isolated from boid snakes with IBD or exposed to IBD. Western blot analysis of viral proteins indicated that viruses isolated from the different snakes were similar. Whether this virus represents the causative agent of IBD is yet to be determined. The isolation of retroviruses from boid snakes with IBD is an important step n the process of identifying the causative agent of this disease. PMID- 11212032 TI - Effects of intraluminal distention and decompression on microvascular permeability and hemodynamics of the equine jejunum. AB - OBJECTIVE: To determine whether intraluminal distention and subsequent decompression of the equine jejunum affects intestinal blood flow, hemodynamics, and microvascular permeability. ANIMALS: 5 healthy adu t horses. PROCEDURES: Horses were anesthestized and underwent exploratory laparotomy. Two jejunal segments were identified as sham-operated or instrumented segments. After baseline values were obtained, intraluminal distention was created in the experimental segment to induce an ntraluminal pressure of 18 cm H2O. After 120 minutes of distention, the intestine was decompressed for 120 minutes. Mesenteric blood flow, oxygen delivery, oxygen consumption, microvascular permeability, wet weight-to-dry weight ratio, neutrophil infiltration, and vascular resistance were determined and comparisons made among control, sham-operated, and experimental segments. RESULTS: Mean jejunal blood flow was 21.4 ml/min per kg. There was a significant decrease in mesenteric bood flow to the distended intestine (13.4 ml/min per kg). Blood flow increased significantly during the decompression period (340% of baseline blood flow). Intraluminal distention and subsequent decompression resulted in a significant increase in microvascular permeability, as determined by the osmotic reflection coefficient. Oxygen delivery and oxygen content decreased significantly during the distention period and increased during decompression. Morphologic evaluation revealed a significant increase in edema and neutrophil infiltration after distention and decompression, compared with results for the sham-operated or control segments. CONCLUSIONS AND CLINICAL RELEVANCE: Intraluminal distention and decompression of the equine jejunum results in low-flow ischemia and edema, which may contribute to adhesions and ileus in the postoperative period after surgery for obstructions of the small intestines. PMID- 11212033 TI - Ultrastructure of selected calcium oxalate-containing urinary calculi from dogs. AB - OBJECTIVE: To elucidate the ultrastructural details of calcium oxalate-containing urinary calculi from dogs. Sample Population-38 specimens selected from a collection of 8,297 oxalate-containing urinary calculi from dogs: 22 specimens composed of calcium oxalate (calcium oxalate monohydrate [COM], calcium oxalate dihydrate [COD], or COM and COD) and 16 specimens composed of calcium oxalate with amorphous calcium phosphate. PROCEDURE: Analyses of specimens included use of plain, reflected, and polarized light microscopy, X-ray diffractometry, scanning electron microscopy (SEM) with backscattered electron (BSE) imagery, and electron microprobe analysis. RESULTS: Four texture types were observed in calcium oxalate calculi; 4 texture types of calcium oxalate-calcium phosphate mixed calculi were recognized. Texture types were delineated through differences in calcium oxalate crystal sizes, which were affected by urine supersaturation and abundance of crystal nucleation sites. Segregation of calcium oxalate from calcium phosphate indicated they do not precipitate under the same conditions. Deposition of calcium phosphate between calcium oxalate crystals decreased the volume of pore spaces within calculi. Porosity was observed along boundaries between COM and COD. Minute pores increased the surface area of calculi exposed to urine, and this increase in liquid-solid interface promotes interaction of crystals with the surrounding urine. CONCLUSIONS AND CLINICAL RELEVANCE: Calcium oxalate urolithiasis is of major concern, because it is often a recurrent disease among dogs, principally treated by surgical removal of calculi, with few effective dissolution strategies. Understanding the ultrastructure and mineralogic content of calcium oxalate and its association with amorphous calcium phosphate is a step toward the solution of this increasingly important medical problem. PMID- 11212034 TI - Effects of changes in power setting of an ultrasonic aspirator on amount of damage to the cerebral cortex of healthy dogs. AB - OBJECTIVE: To determine the minimal ultrasonic aspirator pressure necessary to damage the cerebral cortex of healthy dogs. ANIMALS: 9 mixed-breed dogs. PROCEDURE: The study comprised 2 parts. In part A, 6 dogs were euthanatized immediately prior to the experiment. In part B, 3 dogs were anesthetized for recording of physiologic variables. In both parts, craniectomy and durotomy were performed to bilaterally expose the lateral aspect of the cerebral cortex. An ultrasonic aspirator was placed in contact with various areas of the cerebral cortex, and aspirator power was altered (10, 20, 30, and 40%). Duration of contact at each power was 5 and 10 seconds. Subsequently, gross morphologic and histologic damage was assessed in the cortex. RESULTS: Gross observations for all dogs were similar. At 10% power, visible or histologic damage was not evident in the cortex. At 20% power, the cortex was slightly indented from contact with the hand piece; however, cortical disruption was not evident. Cortical disruption was initially detectable at 30% power in some dogs and was consistently evident at 40% power in both sets of dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Ultrasonic aspirator power of < 20% created minimal acute morphologic damage to the cortex. Power settings between 20 and 30% may superficially damage the cerebral cortex in healthy dogs, whereas 40% power consistently damages the cerebral cortex. Knowledge of the degree of damage to cerebral cortex caused by various amounts of power for ultrasonic aspirators will allow surgeons to avoid damaging normal brain tissues during surgery. PMID- 11212035 TI - Experimental infection of European wild boars and domestic pigs with pseudorabies viruses with differing virulence. AB - OBJECTIVE: To determine susceptibility of European wild boars (Sus scrofa) to infection with pseudorabies virus (PrV) and to characterize the virulence of a wildboar PrV isolate for wild and domestic pigs. ANIMALS: 18 wild boars and 16 domestic pigs. PROCEDURE: Three groups of 4 wild boars were inoculated with PrV Bartha, Kaplan, and a wild-boar isolate (BFW1) and housed with uninfected pigs. Two groups of domestic pigs (4 and 8 pigs/group, respectively) were inoculated with various doses of BFW1. Animals were observed daily for clinical signs, and samples were tested for PrV excretion and homologous antibodies. After reactivation of latent infection by induced immunosuppression, PrV was detected in tissues of necropsied animals, using cell culture and a polymerase chain reaction (PCR). RESULTS: Clinical signs depended on virulence of the PrV strain and dose of inoculum. Only infection with PrV Kaplan resulted in severe disease and death. Virus was isolated from nasal and genital swab specimens. Antibodies were first detected on day 7 after inoculation; a specific humoral immune response was delayed in BFW1-infected animals. Virus was isolated from various tissues of Kaplan-infected wild boars, whereas mainly viral DNA was detected in a few tissues of Bartha- and BFW1-infected animals, using PCR after immunosuppression. CONCLUSIONS AND CLINICAL RELEVANCE: European wild boars are susceptible to transmission of PrV infection from domestic pigs and vice-versa. The PrV isolate BFW1 is of low virulence and seems to be adapted to the wild boar population from which it was isolated. PMID- 11212036 TI - Comparative responses of bronchial rings to mediators of airway hyperreactivity in healthy horses and those affected with summer pasture-associated obstructive pulmonary disease. AB - OBJECTIVE: To compare responses of bronchial rings obtained from healthy horses and horses affected with summer pasture-associated obstructive pulmonary disease (SPAOPD) to selected mediators of airway hyperreactivity in vitro. SAMPLE POPULATION: Bronchial rings from 6 healthy horses and 6 horses affected with SPAOPD. PROCEDURE: Bronchial rings obtained from each group of horses were mounted in organ baths and attached to force transducers interfaced with a polygraph. After applying 2g of tension, each ring was allowed to equilibrate for 45 minutes in Tyrode's solution at 37 C. Cumulative concentration-response relationships to graded concentrations of selected mediators (10(-8) to 10(-4) M) were determined and analyzed for significance at each concentration. RESULTS: Acetylcholine, histamine, 5-hydroxytryptamine, and leukotriene D4 induced concentration-dependent contractile responses in bronchial rings. Prostaglandin F2alpha induced weak and inconsistent contractile responses. The other 2 agents, norepinephrine and substance P, did not induce concentration-dependent responses. Considering the overall group-drug effect, acetylcholine, histamine, 5 hydroxytryptamine, and leukotriene D4 were effective in inducing consistent concentration-dependent contractile responses in both groups. Only 5 hydroxytryptamine and histamine induced significant responses in contractility between groups. The response of bronchial rings from horses with SPAOPD to 5 hydroxytryptamine was significantly greater than those from control horses, whereas the response to histamine was significantly lower. Significant responses were evident at concentrations ranging from 10(-6) to 10(-4) M for both drugs. CONCLUSIONS AND CLINICAL RELEVANCE: Because the airways of horses with SPAOPD had increased responsiveness to 5-hydroxytryptamine in vitro, treatment modalities using 5-hydroxytryptamine antagonists should be investigated to address this phenomenon. PMID- 11212037 TI - Maternal expression of functional lipoprotein lipase and effects on body fat mass and body condition scores of mature cats with lipoprotein lipase deficiency. AB - OBJECTIVE: To assess effects of deficiency of lipoprotein lipase (LPL) on body condition scores and lean and fat body masses of adult cats. ANIMALS: 12 cats without LPL mutations and 23 cats that were heterozygous or homozygous carriers of the Gly412Arg LPL mutation. PROCEDURE: Lean and fat body masses were estimated by use of body condition scores and change in enrichment of serum after IV administration of deuterium oxide. Mass spectroscopy and infrared absorbance methods were used to determine deuterium enrichment. RESULTS: Fat body mass (mean +/- SD; 0.2 +/- 0.1 kg) and percentage body fat (6.2 +/- 1.4%) of homozygotes were significantly less than those of clinically normal cats and heterozygotes (0.7 +/- 0.1 kg, 18.2 +/- 1.6% and 0.5 +/- 0.1 kg, 15.6 +/- 1.7%, respectively). Homozygous offspring of homozygous dams had significantly less fat body mass (0.1 +/- 0.1 kg) and percentage body fat (2.1 +/- 1.0%) than homozygous offspring of heterozygous dams (0.3 +/- 0.1 kg and 9.2 +/- 1.7%, respectively). Lean body mass did not differ significantly among groups. For all groups, percentage body fat was significantly correlated with body condition score (r= 0.65), and body condition scores supported findings for fat body mass. CONCLUSIONS AND CLINICAL RELEVANCE: Deficiency of LPL activity in cats diminishes stores of body fat. This is consistent with a low rate of de novo synthesis of fat. The effect of dam on body masses in mature LPL-deficient cats indicates nutrient programming of adipose formation during gestation or lactation. PMID- 11212038 TI - Use of long-term vaccination with a killed vaccine to prevent fecal shedding of Mycobacterium avium subsp paratuberculosis in dairy herds. AB - OBJECTIVES: To determine whether vaccination with a killed vaccine prevents fecal shedding of Mycobacterium avium subsp paratuberculosis, to compare effectiveness of a culture and cull program in vaccinated and nonvaccinated herds, and to compare paratuberculosis-related preventive management in vaccinated and nonvaccinated herds. SAMPLE POPULATION: 58 commercial Dutch dairy herds. DESIGN: Cross-sectional study (study A) in vaccinated (n = 25) and nonvaccinated (29) herds of dairy cows. Longitudinal study (study B) in vaccinated (n = 2) and nonvaccinated (2) herds of dairy cows. PROCEDURE: In study A, fecal samples were obtained from adult cows in herds with and without a history of vaccination with a killed vaccine. Management measures were evaluated. In study B, fecal samples were obtained 4 times at 6-month intervals from cows older than 6 months. Cows that had positive test results were removed from the herd directly after the outcome of the culture. RESULTS: In study A, differences were not detected among the 25 herds that were vaccinated; culture results were positive for M avium subsp paratuberculosis in 4.4% of herds. In 29 herds that had not been vaccinated, culture results were positive in 6.7%. In study B, the percentage of positive results on culture decreased from 10.9% and 5.7% to 3.5% and 0%, respectively in the 2 vaccinated herds. In the 2 nonvaccinated herds, percentages decreased from 6.1% and 16.5% to 0% and 2.3%, respectively. Management practices were different between herds that were vaccinated and herds that were not; owners of herds that were not vaccinated followed more preventive management procedures and practiced less feeding of raw milk to calves. CONCLUSIONS AND CLINICAL RELEVANCE: Vaccination of calves with a killed vaccine does not prevent transmission of M avium subsp paratuberculosis; therefore, hygienic practices remain essential in herd management. PMID- 11212039 TI - Dystonic reaction after anesthesia. PMID- 11212040 TI - On anesthesia services. PMID- 11212041 TI - Pancuronium added to intravenous regional anesthesia: systemic weakness after prolonged tourniquet inflation time. PMID- 11212042 TI - Subcutaneous tunnelling of interscalene catheters. PMID- 11212043 TI - What do outpatients value most in their anesthesia care? AB - PURPOSE: To determine what outpatients ranked highest in their anesthesia care and whether anesthesiologists could predict that ranking. METHODS: A 36 item mail back questionnaire was administered post-operatively to 45 surgical outpatients and to 15 expert anesthesiologists. Respondents were asked to rank the three highest items from each of four lists of nine items representing pre-operative, intra-operative, pre-discharge and post-discharge outpatient anesthesia care. RESULTS: Complete responses were obtained from 30 outpatients and all anesthesiologists. In each phase of their care (pre-operative, intra-operative, pre-discharge and post-discharge), outpatients ranked highest those elements representing information and communication. Physical conditions of care tend to be least valued. Although anesthesiologists were able to predict what patients valued in the pre and post-discharge phases of their anesthesia care (r = 0.85 and 0.91), they undervalued the importance to patients of communication and information in pre-operative and intra-operative care (r = -0.09 and .65). CONCLUSIONS: Our results reinforce the value that patients place in adequate communication and provision of information in all phases of outpatient anesthesia care, a value that may be underappreciated by anesthesiologists. PMID- 11212044 TI - Remifentanil and controlled hypotension; comparison with nitroprusside or esmolol during tympanoplasty. AB - PURPOSE: To determine whether remifentanil, combined with propofol, could induce controlled hypotension, reduce middle ear blood flow (MEBF) measured by laser Doppler flowmetry, provide a "dry" operative field, and could be compared with nitroprusside or esmolol combined with alfentanil and propofol. METHODS: Thirty patients undergoing tympanoplasty and anesthetized with 2.5 mg x kg(-1) propofol iv followed by a constant infusion of 120 microg x kg(-1) x min(-1), were randomly assigned in three groups to receive either 1 microg x kg(-1) remifentanil iv followed by a continuous infusion of 0.25 to 0.50 microg x kg(-1) x min(-1), or nitroprusside iv, or esmolol iv combined for the latter two groups with alfentanil iv. RESULTS: Controlled hypotension was achieved at the target pressure of 80 mmHg within 107 +/- 16, 69 +/- 4.4, 53.3 +/- 4.4 sec for remifentanil, nitroprusside and esmolol respectively. MEBF decreased by 24 +/- 0.3, 22 +/- 3.3, 37 +/- 3% and preceded the decrease in SABP, within 30 +/- 6.1, 11.2 +/- 3.1, 15 +/- 2.8 sec for remifentanil, nitroprusside and esmolol respectively. Remifentanil, and nitroprusside decreased MEBF autoregulation less than esmolol (0.36 +/- 0.1, 0.19 +/- 0.2, -0.5 +/- 0.2). Controlled hypotension was sustained in all three groups throughout surgery, and the surgical field rating decreased in a range of 80% in all three groups. Nitroprusside decreased pH and increased PaCO2. There were no postoperative complications in any of the groups. CONCLUSIONS: Remifentanil combined with propofol enabled controlled hypotension, reduced middle ear blood flow and provided good surgical conditions for tympanoplasty with no need for additional use of a potent hypotensive agent. PMID- 11212045 TI - Nicorandil accelerates recovery of neuromuscular block caused by vecuronium. AB - PURPOSE: To examine the effect of nicorandil, a K ATP channel agonist, on neuromuscular block caused by vecuronium in patients anesthetized with nitrous oxide, oxygen, isoflurane, and fentanyl. METHODS: Sixty adult patients were allocated to four groups of 15: nicorandil-post-tetanic count (N-PTC), nicorandil train-of-four (N-TOF), control-post-tetanic count (C-PTC) or control-train-of four (C-TOF) group. In the N-PTC and N-TOF groups, 0.1 mg kg nicorandil was given as a bolus followed by an infusion at 1 microg x kg(-1) x min(-1). Two minutes after the bolus, 0.1 mg x kg(-1) vecuronium was administered. In the C-PTC or C TOF group normal saline was given instead of nicorandil. PTC and TOF responses were measured mechanically using a force displacement transducer. RESULTS: Time from the administration of vecuronium to the onset of neuromuscular block in the N-PTC or N-TOF group did not differ from that in the C-PTC or C-TOF group (241 +/ 33 vs 225 +/- 32 sec, mean +/- SD). Times from vecuronium injection to the return of PTC in the N-PTC and C-PTC groups, and those of T1, T2, T3, and T4 (first, second, third, and fourth stimulation of TOF) in the N-TOF and C-TOF groups did not differ. Recoveries of PTC in the N-PTC and C-PTC groups followed similar time course. T1/control twitch height and TOF ratio (T4/T1) in the N-TOF group were higher than those in the C-TOF group 80-120 min and 100-120 min after administration of vecuronium, respectively. CONCLUSION: Nicorandil accelerates recovery of neuromuscular block caused by vecuronium. PMID- 11212046 TI - High concentration sevoflurane induction of anesthesia accelerates onset of vecuronium neuromuscular blockade. AB - PURPOSE: To investigate neuromuscular block using accelography after administration of vecuronium under sevoflurane 8% induction and maintenance with sevoflurane 2% in adults. METHODS: Patients were allocated to three groups: (1) group I: anesthesia was induced and maintained with propofol and fentanyl (n= 15), (2) group II: anesthesia was induced with propofol and maintained with N2O(66%)-O2-sevoflurane 2% (n = 15), (3) group III: anesthesia was induced with sevoflurane 8% using a vital capacity inhalation induction and maintained with N2O(66%)-O2-sevoflurane 2% (n = 15). 0.1 mg x kg(-1) vecuronium was used for paralysis three minutes after anesthetic induction and reversed using intravenous 0.04 mg x kg(-1) neostigmine with 0.02 mg kg atropine when the train-of-four (TOF) ratio returned to 25%. RESULTS: The onset time from initial administration of vecuronium to maximal block in the group III was shorter than that in the groups I and II (139 +/- 35, 193 +/- 35 and 188 +/- 47s, respectively: P < 0.05). The clinical duration from maximal block to 25% recovery of TOF ratio in group II and III was longer than that in the group I (47 +/- 15, 48 +/- 14 and 36 +/- 10 min, respectively: P < 0.05). The reversal times from administration of neostigmine to 75% of TOF ratio in groups II and III were longer than that in the group I (196 +/- 53, 208 +/- 64 and 136 +/- 28s, respectively: P < 0.05). CONCLUSIONS: Vital capacity inhalation induction of anesthesia with sevoflurane accelerates onset and prolongs duration of vecuronium neuromuscular block compared with propofol-fentanyl anesthesia. PMID- 11212048 TI - Anesthesia standards for facilities and equipment. AB - PURPOSE: This article will define standards, how they are developed and applied and how they impact on the day to day practice of clinicians. SOURCE: CSA International, International Electrotechnical Committee (IEC), Organization for International Standardization (ISO). PRINCIPAL FINDINGS: The safety record of the practice of anesthesia has improved over the past 20 yr. This has been brought about by the increase in the knowledge base of physiology and pharmacology, improvements in anesthetic drugs and other medications and through the use of better equipment. However, the introduction of new equipment and the building of new health care facilities has also introduced risks to patient safety. These risks have been created by oversights in design, mistakes in equipment manufacture or facility construction and the need to produce a usable product for the price the health care system can afford. After the anesthetic disasters of the 1960s and 1970s, the need for minimum standards for safety in the design and construction of healthcare facilities and medical equipment were recognized. Canadian anesthesiologists were at the forefront in the development of these standards, and still today members of the Canadian Anesthesiologist's Society are key contributors to the development of both National and International standards. CONCLUSION: Equipment and facility standards have helped improve patient safety over the past 20 yr. However, anesthesiologists need to encourage their governmental regulatory bodies to encourage manufacturer compliance with specific standards. PMID- 11212047 TI - Intraoperative decrease in pulse oximeter readings following injection of isosulfan blue. AB - PURPOSE: Sentinel lymph node mapping, involving injection of isosulfan blue dye around a tumour, is beginning to be used in patients with carcinoma of the breast. Absorption of the dye into the circulation may interfere with pulse oximetry, causing falsely low readings. This report describes changes in pulse oximeter readings following injection of isosulfan blue for sentinel lymph node mapping in a patient with carcinoma of the breast. CLINICAL FEATURES: An 83-yr old female patient underwent sentinel node biopsy of the axilla followed by partial mastectomy for carcinoma of the left breast. Isosulfan blue was injected in the area of the tumour in the left breast. The SpO2 began to decrease 15 min after dye injection, reaching a nadir of 89-90% 30 min after injection. Arterial blood gas analysis showed normal arterial partial pressure of oxygen. Pulse oximeter readings did not return to normal until more than six hours after dye injection. CONCLUSION: Review of the literature reveals a small number of case reports of similar occurrences of low pulse oximeter readings following injection of isosulfan blue or patent blue dye for lymphatic mapping. Data from these reports and the case described here suggest that the latency, magnitude and duration of effect on pulse oximeter readings following injection of these dyes is highly variable. It is important to rule out other causes of low pulse oximeter readings when this effect occurs; normal oxygenation can be verified with arterial blood gas analysis. Co-oximetry can be done to rule out methemoglobinemia as a cause of decreased SpO2. PMID- 11212049 TI - Lateral recumbent head-down posture for epidural catheter insertion reduces intravascular injection. AB - PURPOSE: The unintentional and unrecognized cannulation of an extradural vein is a potentially serious complication of an epidural anesthetic. The present study was undertaken to assess the incidence of blood vessel puncture related to epidural catheterization performed in three different body positions. METHODS: The study was conducted in 900 (three groups of 300) obstetric patients undergoing continuous epidural analgesia during their labour and who were randomly allocated to three groups. Epidural catheterization was performed with patients in the sitting, lateral recumbent horizontal, or lateral recumbent head down position. RESULTS: There was a lower incidence of vessel cannulation when this procedure was performed in the lateral recumbent head-down position (2%) than in the lateral recumbent horizontal (6%) and in the sitting position (10.7%). CONCLUSION: Adoption of the lateral recumbent head-down position for the performance of lumbar epidural blockade, in labour at term, reduces the incidence of lumbar epidural venous puncture. PMID- 11212050 TI - Epidural naloxone reduces intestinal hypomotility but not analgesia of epidural morphine. AB - PURPOSE: Epidural morphine is associated with decreased bowel motility and increased transit time. Low doses of intravenous naloxone reduce morphine-induced pruritus without reversing analgesia, but the effect of epidural naloxone on bowel motility has not been studied. Therefore we evaluated bowel motility and analgesia when naloxone was co-administered with morphine into the epidural space. METHODS: Forty-three patients having combined thoracic epidural and general anesthesia for subtotal gastrectomy were randomly assigned to one of two study groups. All received a bolus dose of 3 mg epidural morphine at the beginning of surgery, followed by a continuous epidural infusion containing 3 mg morphine in 100 ml bupivacaine 0.125% with either no naloxone (control group, n = 18) or a calculated dose of 0.208 microg x kg(-1) x hr(-1) of naloxone (experimental group, n = 25) for 48 hr. We measured the time to the first postoperative passage of flatus and feces to evaluate the restoration of bowel function, and visual analog scales (VAS) for pain during rest and movement. Scores were assessed at 2, 4, 8, 16, 24, 36 and 48 hr postoperatively. RESULTS: The experimental group had a shorter time to the first postoperative passage of flatus (5 1.9 +/- 1 6.6 hr vs 87.0 +/- 19.5 hr, P < 0.001 ) and feces (95.3 +/- 25.0 hr vs 132.9 +/- 29.4 hr, P < 0.001). No differences were found in either resting or active VAS between the two groups. CONCLUSION: Epidural naloxone reduces epidural morphine-induced intestinal hypomotility without reversing its analgesic effects. PMID- 11212052 TI - Improving quality of anesthesia care: opportunities for the new decade. PMID- 11212051 TI - Antinociceptive and cardiovascular properties of esmolol following formalin injection in rats. AB - PURPOSE: To assess the role of esmolol, a beta1 receptor blocker, in the modulation of pain in the absence of anesthesia. METHODS: Rats were chronically instrumented to record mean arterial blood pressure (MAP) and heart rate (HR). Animals were divided into three groups. Group 1 [esmolol high (EH) 150 mg x kg( 1) x hr(-1); n = 9], Group 2 [esmolol low (EL) 40 mg x kg(-1) x hr(-1); n = 7] and Group 3 saline (n = 9). Formalin 5% was injected in the rat hind paw. Formalin-induced lifting, MAP and HR were recorded at five minute intervals for 35 min after formalin injection. RESULTS: Formalin was associated with an early (Phase 1; 0-5 min) and late nociceptive response (Phase 2; 10-35 min). Esmolol did not affect Phase 1. Although low dose esmolol had minimum effects on nociceptive Phase 2, it was diminished with high dose esmolol. Formalin induced biphasic increases in MAP and HR. Although esmolol did not affect the initial increase in MAP, high dose esmolol blunted the secondary increase in MAP Both low and high doses of esmolol inhibited formalin-induced tachycardia during the first 30 min. CONCLUSION: Our data suggest that esmolol leads to analgesia and reduction of cardiovascular responses to pain. PMID- 11212053 TI - Anterior mediastinal tumour identified by intraoperative transesophageal echocardiography. AB - PURPOSE: To report a child with anterior mediastinal tumour misdiagnosed as pericardial effusion who had been sent to the operating theatre for drainage. After induction of general anesthesia she developed cardio-respiratory collapse. The diagnosis was made with the aid of transesophageal echocardiography (TEE). CLINICAL FEATURES: A 14-yr-old girl suffered from cough and intermittent fever for one month before admission. Four days before admission, she became orthopneic and was admitted to the intensive care unit. Precordial echocardiography showed an anterior and posterior echolucent space between the pericardium and epicardium that was thought to be a pericardial effusion. She was sent to the operating room for emergency drainage. After induction of general anesthesia, breath sounds were not heard on the left side of the chest. The patient developed increasing hypoxemia and hypotension despite cardiocentesis. A TEE determined that an anterior mediastinal mass was the cause of her hypoxemia and hypotension. The tumour was debulked and the patient made an uneventful postoperative recovery. CONCLUSION: In this case, the correct diagnosis of an anterior mediastinal mass was made with TEE. The place of TEE may be indicated in patients with unexplained hypoxemia and hypotension. PMID- 11212054 TI - Neutrophilia and granulocyte colony-stimulating factor levels after cardiopulmonary bypass. AB - PURPOSE: The precise mechanism of neutrophilia after cardiac surgery is unknown. Granulocyte colony stimulating factor (G-CSF) can increase the number of leukocytes. The purpose of this study was to evaluate the relationship between serum G-CSF levels and peripheral blood leukocyte counts after cardiac surgery. METHODS: We prospectively studied 10 patients undergoing cardiac surgery (coronary artery bypass grafting) using cardiopulmonary bypass (CPB). Plasma G CSF levels and neutrophil count were measured before induction of anaesthesia, at the end of surgery, and on the first postoperative day. These changes were compared with those in patients undergoing non-cardiac major surgery (control group). RESULTS: At the end of surgery, G-CSF levels increased (P < 0.01) in both groups, but were higher in the control than in the cardiac group (3,250 +/- 690 vs 194 +/- 29.5 pg ml(-1), respectively, mean +/- SEM, P < 0.01). On the first postoperative day, G-CSF levels were still high in both groups, and were still higher in the control (710 +/- 179 vs 122 +/- 19.9, respectively, P < 0.01). However, neutrophilia was greater in the cardiac group than in the control. G-CSF response correlated positively with neutrophilia in the control group (r = 0.656, P < 0.05) but not in the cardiac group. CONCLUSIONS: Our results indicate that changes in leukocyte count following cardiac surgery are unique to patients undergoing CPB. G-CSF plays an important role as the mediator of neutrophilia after non-cardiac surgery, but not after cardiac surgery with CPB. PMID- 11212055 TI - Increase of peak expiratory flow by atropine is dependent on circadian rhythm. AB - PURPOSE: To examine whether the bronchodilatory effect of atropine differs in the evening from the morning. METHODS: Thirteen adult healthy volunteers with no oral medication intake were studied. At 1600, peak expiratory flow (PEF) was measured three times, and the highest value recorded. Subsequently, the volunteer received 0.01 mg(-1) x kg(-1) atropine im, and the PEF was measured every 30 min for 180 min. On a different day, at 0400, the effect of atropine on the PEF was measured again in the same way. RESULTS: The PEF values before atropine at 1600 and 0400 were 485 +/- 92 (350-730) and 458 +/- 76 (340-600) 1 min(-1),(P < 0.05). There was no difference in PEF values between the 1600 and 0400 time courses after atropine. The PEF value was increased only at 90 min at 1600 (P = 0.0012), but at 30, 60, 90 and 120 min at 0400 (P = 0.0001). CONCLUSION: Atropine administration has a weak bronchodilatory effect in the evening, but a stronger effect in the morning. Airways are narrower in the morning than in the evening, and this change is inhibited by atropine such that the PEF values are restored to those observed in the evening. PMID- 11212056 TI - Amniotic fluid embolus: a review of the literature. AB - PURPOSE: To review the literature since 1979 to determine the natural history, etiology, diagnosis and potential treatment of amniotic fluid embolus (AFE). SOURCE: English language articles and books published between June 1976 and June 1998 were identified by a computerized medline search using the title or text word amniotic fluid embolus. This same search strategy was repeated and updated to October 1999 by an independent individual using both Medline and Embase. The search was also expanded to include Science Citation Index listing Morgan's 1979 review article. All relevant publications were retrieved and their bibliographies were scanned for additional sources. PRINCIPAL FINDINGS: Randomized controlled trials are not possible with amniotic fluid emboli. The majority of the literature consists of clinical reports combined with occasional limited reviews. Knowledge obtained from these reports suggests that amniotic fluid emboli present as a spectrum of disease that ranges from a subclinical entity to one that is rapidly fatal. Because cases are sporadic and the diagnosis is often unconfirmed, little progress has been made towards understanding its etiology or defining the risk factors. Present management is empirical and directed towards the maintenance of oxygenation, circulatory support and the correction of coagulopathy. CONCLUSION: Amniotic fluid embolus continues to be a life threatening but potentially reversible complication unique to pregnancy. It cannot be predicted nor prevented. Review of the literature reveals that there are no standardized investigational methods or protocols to confirm the diagnosis in suspected cases. PMID- 11212057 TI - Assessment of risks of hypertension and benefits of treatment--a difficult matter. PMID- 11212058 TI - Left ventricular hypertrophy is associated with an attenuated endothelium dependent vasodilation in hypertensive men. AB - To investigate the relationship between left ventricular hypertrophy (LVH) and endothelium-dependent vasodilation (EDV), 30 untreated hypertensive patients, 18 treated hypertensives (53 +/- 7 years, all males) and 26 age-and sex-matched healthy normotensive controls, underwent evaluation of EDV and endothelium independent vasodilation (EIDV) in the forearm, by means of local intra-arterial infusions of methacholine (MCh, evaluating EDV) and sodium nitroprusside (SNP, evaluating EIDV). Forearm blood flow was measured by venous occlusion plethysmography and LVH was measured by echocardiography. The reduction in forearm vascular resistance during MCh infusion (4 microg/min) was significantly smaller in the hypertensive patients with LVH when compared to those without LVH, both in the untreated (-61 +/- 12%, n = 19 vs -72 +/- 4%, n = 11, p < 0.01) and in the treated group (-60 +/- 15%, n = 11 vs -75 +/- 5%, n = 7, p < 0.01). Thereby, EDV was significantly impaired only in the hypertensive patients with LVH when compared to controls (-77 +/- 7% at MCh 4 microg/min, p < 0.001). EIDV was not significantly different between patients with and without LVH and controls. In conclusion, the presence of LVH was related to endothelial dysfunction, both in untreated and treated hypertensive patients, suggesting either a role for endothelial function in the development of LVH, or that a dysfunctional endothelium and LVH are coexisting markers of a more severe hypertensive disease. PMID- 11212059 TI - Does hypertension or a previous myocardial infarction influence the blood pressure and heart rate responses to changes in body position? Results from a study with serial measurements in the supine and standing positions in 60-year old men. AB - An age-related attenuation of the normal increase in diastolic blood pressure and heart rate upon standing has previously been observed in man. Whether this is due to ageing as such, or a consequence of a higher prevalence of cardiovascular disease in older compared to younger subjects, is unclear. This population-based study was conducted to address this question. It was carried out in three groups of 60-year-old men: (i) with hypertension (n = 75), (ii) with a previous myocardial infarction (n = 39), and (iii) without any of these diseases, thus constituting a control group (n = 41). Blood pressure and heart rate were assessed during three 7-min periods (supine-standing-supine), using an unbiased non-invasive method. The cardiovascular responses were both qualitatively and quantitatively similar in all three groups, i.e. the increases in diastolic blood pressure and heart rate upon standing, and decreases upon laying down, were of a similar magnitude. In conclusion, 60-year-old men with hypertension or a previous myocardial infarction had blood pressure and heart rate responses similar to those of men of the same age who did not have these diseases. This indicates that the attenuated response previously reported in older compared to younger people is not explained by the higher prevalence of these cardiovascular diseases in the elderly, but is merely an age-dependent characteristic. PMID- 11212060 TI - How accurate are hypertension treatment decisions? Absolute risk assessment and prescribing for moderate hypertension--a study of Cambridge general practitioners. AB - OBJECTIVE: To determine the factors influencing general practitioners' prescribing for patients with moderate hypertension, and to investigate their ability to assess patients' absolute risk of cardiovascular disease. DESIGN: Decision-making was assessed by a postal questionnaire involving five standardised example patients, send to all general practitioners in the CB postcode area (Cambridge, UK). Patients varied in age, gender, diabetic and smoking status, blood pressure and total cholesterol, giving 5-year absolute risks ranging from less than 5% to greater than 20%. GP treatment decisions and risk factor influence, age bias, absolute risk calculations and cost-awareness were analysed with SPSS. Absolute risk was calculated using the New Zealand Core Services Committee (NZCSC) Guidelines, 1995. RESULTS: GP response rate was 66%. Sample demographics (mean age 42 years, 39% female) did not differ statistically from local health authority data. High blood pressure alone was the most common reason for instituting therapy (67%), independent of other risk factors. Drug choices did not differ statistically from Prescription Pricing Authority data. This supports the validity of the questionnaire. GP estimations of absolute risk were inconsistent, and there was a significant association between underestimation of elderly patient risk and overestimation of younger patient risk (p = 0.05). CONCLUSIONS: The Cambridge GPs more frequently based treatment decisions on patients' blood pressure level alone, rather than considering absolute risk as recommended by NZCSC and WHO guidelines. The relationship between patient age and risk estimations may indicate a "young age premium" influencing treatment. The data support the need for risk-based guidelines and education in treatment of hypertension. PMID- 11212061 TI - Self-reported side-effects of antihypertensive drugs: an epidemiological study on prevalence and impact on health-state utility. AB - The aim in this study was to assess the frequency and type of self-reported side effects among hypertensives in a general population, and to estimate the relationship between drug use and side-effects and health utility using the Rating Scale (RS) method. The study is based on a postal questionnaire that was sent to a random sample of 8000 inhabitants aged 20-84 years (response rate 68%) in Uppsala County, Sweden, in 1995. The results showed that nearly 20% of the users of antihypertensive drugs reported side-effects. Men and women reported side-effects to nearly the same extent. In the linear regression analyses, those with hypertension, with or without medication, rated lower health utilities (-6.0 and -7.1 respectively) than did normotensives after controlling for age and sex. The lowest value, -8.7, was found among drug users who experienced side-effects. Side-effects causing impotence and emotional distress, i.e. insomnia, tiredness and depression had the strongest negative impact on health utility. To conclude, the study showed that side-effects among hypertensives are common. Both the disease and the drug treatment adversely affect the patient's well-being. However, drug treatment was of less importance than that found in prior studies. The findings here stress that side-effects should be taken into greater consideration when evaluating drug treatment. PMID- 11212062 TI - The placebo effect and white coat effect in isolated systolic hypertension and systo-diastolic hypertension. AB - It is well recognised from many clinical trials that there is a blood pressure lowering effect when placebo is administered to patients with essential hypertension ("placebo effect"). The reduction in blood pressure, however, may also be partly due to loss of the alerting response ("white coat effect") as a result of familiarisation with the clinical environment. To investigate the hypothesis that there may be a more marked placebo effect and white coat effect in isolated systolic hypertension (ISH) compared with systo-diastolic hypertension (SDH), we studied 78 patients with hypertension: 34 had ISH and 44 patients had SDH. The 34 patients with ISH were older (68.7 vs 54.9 years), had a higher SBP (192.2 vs 169.6 mmHfg) and lower DBP (85.5 vs 102.0 mmHg) when compared to patients with SDH. Amongst the patients with ISH, there were no significant changes in mean blood pressures pre-placebo (paired t-test, p = NS). In the placebo period, there was a significant reduction in systolic blood pressures at all three points, and a significant reduction in diastolic blood pressures after 2 and 3 months placebo (paired t-test, p < 0.05). There was a mean reduction in mean systolic blood pressure at visit 1 by 5.2%, visit 2 by 5.1% and visit 3 by 4.6%, when compared to mean pre-placebo systolic blood pressures (p < 0.05). The mean reduction in diastolic blood pressure was 5.8% at visit 2 and 3.5% at visit 3, when compared to mean pre-placebo diastolic blood pressure (p < 0.05). At the 4-week visit after receiving placebo, the mean systolic blood pressure decreased by 9.4 mmHg (p = 0.003) and mean diastolic blood pressure by 2.7 mmHg (p = NS) in the patients with ISH. In patients with SDH, there were no statistically significant changes in recorded BP readings following the introduction of placebo. We suggest blood pressures in some patients with ISH may settle with careful follow up and initiation of treatment in these patients could potentially be delayed for at least 3 months, as therapy may not prove necessary. PMID- 11212063 TI - Less difference between office and ambulatory blood pressure in women than in men both before and during antihypertensive treatment. AB - In 199 subjects (56% women) with a diastolic blood pressure (BP) of 95-115 mmHg, 5 mg of either amlodipine or felodipine extended release (ER) was given for 4 weeks following 4 weeks of placebo-treatment. BP was measured by conventional clinic BP technique and by 24-h ambulatory BP monitoring (Spacelab 90202/90207). Men and women had identical clinic BP at baseline and it was lowered equally much by 4 weeks of treatment (men: 158/101 and 147/93, women: 159/102 and 149/93 mmHg, respectively). However, ambulatory BP was higher in women than in men both before and after treatment (men: 145/91 and 134/85, women: 149/95 and 140/89 mmHg, respectively, p < 0.05 for both comparisons). The difference between clinic BP and daytime ambulatory BP was higher in men than in women (systolic men: 8.1 +/- 14, women: 3.7 +/- 15 mmHg, respectively, p = 0.04; diastolic men: 5.5 +/- 8.0, women: 2.1 +/- 8.3 mmHg, p = 0.004). The correlation between the treatment effect measured by ambulatory and clinic BP was poor (systolic r = 0.26, p < 0.0001; diastolic r = 0.17, p = 0.03) and was unaffected by exclusion of subjects with normal ambulatory BP. The poor correlation between treatment effects measured as clinic and ambulatory BP is intriguing, and suggests that using ambulatory BP instead of clinic BP for monitoring the treatment of hypertension could affect the clinical outcome. PMID- 11212064 TI - Long-term renal and cardiovascular effects of antihypertensive treatment regimens based upon isradipine, perindopril and thiazide. AB - The aim of this study was to describe the renal function (renal hemodynamics, water and sodium handling) and its relation to cardiovascular structural changes in a population of essential hypertensive patients before and after antihypertensive treatment. Glomerular filtration rate and renal plasma flow were measured by a constant infusion technique. The reference substances used were [131I]iodohippurate (Hippuran) and [125I]iothalamate. The lithium clearance method was used for measuring renal water and sodium handling. Microalbuminuria was measured. A subcutaneous gluteal biopsy was taken and the media thickness to lumen diameter ratio of small resistance vessels was determined. Left ventricular mass index was determined by echocardiography. Thirty-seven patients with newly diagnosed or poorly controlled essential hypertension were randomized to treatment with regimens based upon either isradipine, perindopril or hydrochlorothiazide-amiloride. Atenolol and hydralazine were added as secondary and tertiary drugs, respectively, when needed for normalization of diastolic blood pressure. Investigations were performed before and after 9 months of normalization of blood pressure. Renal function in untreated hypertensive patients was characterized by increased renal vascular resistance, decreased renal blood flow, normal glomerular filtration fraction and normal serum creatinine. No association was found between peripheral resistance vessel structure in subcutaneous vessels and renal hemodynamic parameters. Patients with severe left ventricular hypertrophy (left ventricular mass >360 g) had lower glomerular filtration fraction, greater renal vascular resistance, lower renal blood flow and increased microalbuminuria in comparison with patients with less pronounced cardiac changes. After 1 year of treatment, which had a profound effect on heart and vessel structure, renal hemodynamics were unchanged in patients receiving antihypertensive treatment regimens based on the ACE inhibitor perindopril or the Ca-antagonist isradipine, whereas renal plasma flow was reduced, glomerular filtration rate preserved and filtration fraction significantly increased in those treated with a regimen based on diuretics. The serum creatinine concentration was decreased in the former group, whereas it was unchanged in the latter two. Significantly detrimental effect on uric acid homeostasis was only found in patients treated with a regimen based on diuretics. PMID- 11212066 TI - Treatment of hypertension in patients with type-2 diabetes mellitus. PMID- 11212065 TI - Comparative study of home and office blood pressure in hypertensive patients treated with enalapril/HCTZ 20/6 mg: the ESPADA study. AB - The introduction and generalization of 24-h ambulatory blood pressure (BP) monitoring has shown the clinical relevance of home BP. The aim of this study was to assess the validity of home-measured BP for monitoring and controlling patients with arterial hypertension while on a homogeneous treatment. An additional objective was to establish the degree of office BP control obtained. This was a prospective, longitudinal, observational and multicenter study in a cohort of 156 patients of both sexes, aged over 18 years and with essential hypertension. All of them received the fixed combination enalapril/HCTZ 20/6 mg as the only hypertensive agent for at least 4 weeks previously. Office BP was the average of three measurements. For home BP, a semi-automated device (OMRON HEM 705 CP) was used. The patients measured their BP twice a day for 2 consecutive days. The average differences between the two measuring methods were low, but significant: 3.99 mmHg for systolic BP (SBP; p < 0.05), 2.02 mmHg for diastolic BP (DBP; p < 0.05). Pearson's regression coefficient between the office and home values was highly significant (p < 0.0001) for SBP, DBP and heart rate. Home BP measurement was highly reproducible as shown by the high within-class correlation coefficient for individual measurements on the first day compared with the second: 0.88 (95% confidence interval, CI 0.82-0.92; p < 0.00001) for SBP and 0.89 for DBP (95% CI 0.83-0.93; p < 0.00001). The percentage of patients with strict office DBP and SBP control (< 140/90 mmHg) was 61.3% and with DBP control (<90 mmHg) 92%. In conclusion, in the ESPADA study, the application of home BP measurement is valid, reproducible and shows a high correlation with office BP. PMID- 11212068 TI - Endometriosis: candidate genes. AB - Endometriosis is generally regarded as a benign disease but it does exhibit some characteristics reminiscent of malignancy. This raises the possibility that, like malignant diseases, the development of endometriosis may involve the acquisition of somatic genetic alterations in genes that regulate cell growth and differentiation. Studies over the past few years have substantiated this view with the identification of a variety of genetic abnormalities usually only associated with malignancies. Our own studies have shown that genetic alterations, as shown by loss of heterozygosity, are relatively common in endometriosis implying that tumour suppressor gene inactivation is likely to be involved in the proliferation and maintenance of all endometriotic implants. We have also shown by DNA fingerprinting that endometriotic lesions found adjacent to ovarian cancers have a common lineage, reinforcing the compelling histological and epidemiological data that endometriosis is a precursor of endometrioid and clear cell ovarian cancers. It is now well accepted that susceptibility to endometriosis may also involve an inherited genetic component. Studies aimed at identifying the predisposing genes are still in their infancy but should eventually provide invaluable insights into the pathology and aetiology of endometriosis. PMID- 11212067 TI - The possible biological and reproductive functions of ubiquitin. AB - The protein ubiquitin (Ub) appears to be present in all eukaryotic cells. Its widespread presence and extremely conserved structure indicate that it may play a vital role in cell metabolism. The roles of Ub are mediated by its covalent attachment to target proteins, a process known as ubiquitylation, a form of protein modification which may lead to degradation of the modified protein. A number of proteins with similar structure to Ub but varying in function have been isolated. Recently, there has been much interest in the role of Ub and its related proteins in reproductive processes. Ub and Ub-related proteins may be involved in gametogenesis, modulation of steroid receptor concentrations, placental development and endometrial modification at the beginning of pregnancy. These wide-ranging effects have led to extensive research which will be reviewed in this article. PMID- 11212069 TI - Outcome and follow-up of children born after IVF-surrogacy. AB - This study addresses various outcomes and follow-up of children born after IVF surrogacy. Recent reports on perinatal outcome after IVF-surrogacy and on data generated by the Society of Assisted Reproductive Technology (SART) Registry between 1991 and 1995 were examined. A review of recently published perinatal outcomes of children born after IVF-surrogacy, including the developmental information of 110 children after the first 2 years of life, was undertaken. The birth weights for singleton pregnancies following IVF-surrogacy and IVF were similar, whereas the birth weights of twins and triplets born from the IVF surrogates were significantly heavier than those delivered from conventional IVF patients. Preterm delivery was increased in twin and triplet gestations in all segments analysed. The incidence of low birth weight was significantly lower in children born after IVF surrogacy than in those born after IVF, for all births recorded. The incidence of congenital abnormalities following IVF and IVF surrogacy was within the expected range for spontaneous conceptions. Speech delays were predominant in the multiple births, but neither speech nor motor delays persisted at 2 years of age in children born after IVF-surrogacy. These findings would imply that a gestational carrier would provide potential environmental benefits for the infant. PMID- 11212070 TI - Pregnancy and child outcome after oocyte donation. AB - During the last decade oocyte donation has been highly successful for treating women previously thought to be hopelessly infertile. The pregnancy rate after oocyte donation is among the highest reported for any fertility-enhancing procedure. Most investigators have noted an increased rate of obstetric complications in these pregnancies. In particular, pregnancy-induced hypertension appears to occur more often than expected, and the Caesarean section rate is high. However, the majority of oocyte recipients experience a favourable pregnancy and perinatal outcome. When perinatal complications occur they are usually related to multiple gestation. The high frequency of multiple pregnancy after oocyte donation, as well as in all other fields of assisted reproduction, deserves attention, and efforts to avoid multi-fetal gestation must be made. There are only a few studies on post-natal growth and development of young children born after oocyte donation. The health of these children appears to be within normal ranges. The psychological consequences of the treatment on the child require further investigation. Thus far, studies have shown normal socio emotional development in the child and a warm relationship between the parents and the child in oocyte donation families. PMID- 11212071 TI - Polycystic ovarian disease: heritability and heterogeneity. AB - The polycystic appearance of the ovary is the distinguishing characteristic of polycystic ovary syndrome (PCOS) but there is a wide range of other clinical and biochemical features, e.g. elevated serum concentrations of androgens, insulin, LH and decreased insulin sensitivity. The high prevalence of affected individuals and the wide range of related phenotypes can be explained by the interaction of a small number of key genes with environmental factors. Heritability of PCOS has been inferred from studies of the syndrome in various populations (ethnic groups, twins and PCOS families). The data suggest that the condition is passed down through either sex, according to an autosomal dominant model of genetic transmission. To date, specific gene mutations affecting androgen synthesis, insulin secretion and insulin activity explain most of the endocrine and metabolic symptoms, while environmental risk factors (either during prenatal or post-natal life), seem to convert an occult PCOS into a clinically manifest syndrome. PMID- 11212073 TI - Review: parent-child relationships and child development in donor insemination families. AB - The present article reviews the empirical research regarding the parent-child relationships and the development of children in donor insemination (DI) families. Over the years, follow-up studies have appeared sporadically and, despite the varying quality of the research methods, preliminary findings have emerged. Heterosexual DI parents were psychologically well adjusted and had stable marital relationships. DI parents showed a similar or higher quality of parent-child interaction and a greater emotional involvement with their children compared with naturally conceived families. The majority of studies which investigated several aspects of child development found that, overall, DI children were doing well. Findings with regard to emotional/behavioural development, however, were divergent in that some studies identified an increase of such problems while others did not. A steadily growing group within the DI population is lesbian mother families. More recently, follow-up studies have been carried out among DI children who were raised from birth by two mothers. Despite many concerns about the well-being of these children, no adverse effects of this alternative family structure on child development could be identified. As the DI children in all investigations were still young, our knowledge about the long term effects of DI remains incomplete. PMID- 11212072 TI - Follow-up studies of children born after frozen sperm donation. AB - The need to assess the health of children born after assisted reproductive technologies (ART) using frozen donor spermatozoa has been a major concern for the last decade. Most available published studies are confusing (since they are retrospective) and refer to small numbers of cases or involve a bias. Two prospective and large population-based studies have been published, one in France and the other in Australia. The general characteristics of children born after ART using frozen spermatozoa was unchanged in comparison with the general population (weight, prematurity, stillbirths, sex ratio). However, the rate of multiple pregnancy was increased, first in artificial insemination with donor semen (AID), where the use of hormonal treatment may be too heavily prescribed, and second in IVF with donor semen (IVF/D) where both the ovulation induction treatments and embryo transfer policy increase the rate of multiple pregnancies. As far as birth defects or chromosomal abnormalities are concerned, no difference has been observed from the general population. Finally, the use of frozen spermatozoa does not seem to affect the health of children conceived by AID or IVF/D. The psychosocial development of such infants is not as well known because of the confidentiality in many countries concerning sperm donation. However, the available information on the psychosocial development of these children up to the age of 8-10 years appears to be reassuring. Larger and longer studies are needed to answer such questions, particularly with regard to adulthood. PMID- 11212074 TI - Varicocele and male infertility: part I. Preface. PMID- 11212075 TI - Varicocele as a progressive lesion: positive effect of varicocele repair. AB - Varicoceles are the leading correctable cause of infertility in men who present to an infertility clinic for evaluation. Consequently, the surgical correction of a varicocele, known as a varicocelectomy, is the most commonly performed operation for the treatment of male infertility. The current data suggest that an individual with a varicocele, even with a previously normal semen analysis or documentation of previous fertility, is at risk for subsequent loss of testicular function and infertility. Many of these patients will need to be treated because there is convincing evidence that a varicocele may have a progressive toxic effect on the testes that may ultimately result in irreversible infertility if left untreated. Identifying those individuals with varicoceles that will ultimately cause fertility impairment is still beyond our current clinical capabilities. Current investigative modalities, e.g. semen analysis, testicular measurement, serum gonadotrophin determination, gonadotrophin-releasing hormone (GnRH) stimulation test, and testis biopsy analysis, may be employed to detect early changes in testicular physiology produced by a varicocele. PMID- 11212076 TI - Effects of varicocele on male fertility. AB - Varicoceles are vascular lesions of the pampiniform plexus and are the most common identifiable abnormality found in men being evaluated for infertility. Despite the long history associated with varicoceles, there remains much controversy regarding their diagnosis and management. The purpose of this manuscript is to address three of the most pressing controversies: (i) the association of varicoceles with male infertility, (ii) whether varicoceles exert a progressive deleterious effect and (iii) the relationship of varicocele size and outcome following varicocele repair. The current literature is reviewed in an effort to answer these questions. Based upon this analysis, conclusions can be drawn regarding the best management of varicoceles in subfertile men, adolescents, young fertile men and men with subclinical varicoceles. Although there remain many controversies due to a paucity of data, there appears to be a significant difference between adults and adolescents with respect to a progressive deterioration of semen parameters and it is clear that subclinical varicoceles do not play a major role in male infertility. PMID- 11212077 TI - Varicocele treatment in the light of evidence-based andrology. AB - Treatment of varicoceles became the most common treatment for male infertility merely on an empirical basis. However, in the age of evidence-based medicine it is surprising that only a few, and mainly recent, randomized controlled clinical trials with relevant outcome parameters have been published to allow adequate judgement of treatment effectiveness. Moreover, difficulties in study design could also be detected in most of these high-quality studies. Despite these difficulties and in contrast to the majority of uncontrolled studies on varicocelectomy, meta-analysis of these randomized controlled clinical studies involving 385 patients showed no significant treatment benefit and questions the common practice of varicocelectomy. Even the high-quality studies show conflicting results and therefore the topic of varicocele treatment will remain controversial and further randomized clinical trials should readdress this issue. For the time being, intervention by surgical or angiographic occlusion of the spermatic vein cannot be recommended. PMID- 11212078 TI - The varicocele dilemma. AB - There is probably no subject that is more controversial in the area of male infertility than varicocele. The overwhelming majority of non-urologist infertility specialists in the world are extremely sceptical of the role of varicocele or varicocelectomy in the treatment of male infertility. Directors of most assisted reproductive technologies (ART) programmes view the enthusiasm with which urologists approach varicocelectomy as a potential impediment to the couple that is getting older and do not have much time left to become pregnant using ART. There are many credible, well-controlled studies which show no effect of varicocelectomy on fertility. There are also a few 'controlled' studies that favour varicocelectomy, but all can be criticised on the basis of patient selection bias. Thus the great weight of evidence from controlled studies is against varicocelectomy and the reports supporting varicocelectomy are extremely weak. Finally, the reports that semen parameters are improved by varicocelectomy is flawed by uncontrolled observations and the failure to take into account the variability of semen analysis in infertile men and its regression toward the mean. Many control studies have demonstrated that, because of this variability, men with an initially low sperm count tend later to have higher sperm counts in the absence of any treatment whatsoever. PMID- 11212079 TI - The study of varicocele through the use of animal models. AB - The pathophysiology of the varicocele has received considerable study, both in humans and in animal models. Mechanistic information is difficult to obtain from human subjects because study designs must not be invasive and the subject population is variable in the status of the varicocele, patient age, fertility or other health-related issues. Because of these limitations, animal models of varicocele have been developed in several species, the most common being the rat. Surgery to establish the varicocele involves partial obstruction of the left renal vein, causing a varicosity of the left spermatic vein, including the pampiniform plexus. Studies using this model have shown that experimental left varicocele induces bilateral increases in testicular blood flow and temperature contemporaneous with decreases in intratesticular testosterone and testicular sperm output. Spermatic vein reflux is not related to the pathophysiological consequences of experimental varicocele. Many questions remain regarding the mechanism by which varicocele induces testicular dysfunction, chief among them being how the unilateral varicocele causes a bilateral testicular response in the first place. PMID- 11212081 TI - Haematopoietic stem cell transplantation and gene therapy in the fetus: ready for clinical use? AB - Allogeneic haematopoietic stem cell transplantation in utero has been successfully used for the prenatal treatment of severe combined immunodefiency syndrome. However, this treatment has not been successful in the therapy of other conditions in which the fetus is immunologically competent. The main obstacles to success are lack of competitive advantage of donor versus host stem cells, preventing stable engraftment and graft rejection. Several strategies are being explored to overcome these problems, and some of them have been successful in animal studies. Prenatal gene therapy, using ex-vivo transduced autologous haematopoietic cells or direct gene targeting in utero, is another potential approach in the treatment of immunocompetent fetal recipients. Although this has been shown to be feasible in animal models, safety concerns regarding transduction of fetal germ cells or maternal cells should be addressed in preclinical experiments prior to initiation of clinical trials. PMID- 11212080 TI - Leiomyomata: heritability and cytogenetic studies. AB - Leiomyomata represent the most common gynaecological tumour in women of reproductive age, and are the primary indication for hysterectomy in the USA. Cytogenetic and genetic studies have, in recent years, advanced our understanding of the aetiology of these tumours. Cytogenetic aberrations involving chromosomes 6, 7, 12 and 14 constitute the major chromosomal abnormalities seen in leiomyomata, and suggest the possibility that disruption or dysregulation of the genes HMGIC and HMGIY may contribute to the development of these tumours. Based on the finding of a variety of chromosomal aberrations detected in fibroids, other genes with fundamental roles in the pathobiology of uterine leiomyomata await identification. Furthermore, the incidence of fibroids has been shown to be greater in African-American women than in Caucasian women. The existence of a heritability component of uterine leiomyomata has been further implicated by twin pair studies and the existence of familial forms of leiomyomata, both of which suggest an inherited diathesis for leiomyomata formation. This paper will review the cytogenetic aberrations and gene expression, with respect to their contributions to the pathogenesis of leiomyomata, and also summarize the current understanding of heritability of these tumours. PMID- 11212082 TI - Efficacy of nafarelin in assisted reproductive technology: a meta-analysis. AB - A systematic review identified nine randomized, controlled trials (both published and unpublished) which assessed the efficacy of nafarelin during IVF compared with other gonadotrophin-releasing hormone (GnRH) agonists. The trials included 1,014 women (nafarelin n = 597) in protocols employing three different dosage regimens, long and short stimulation protocols, and three comparative GnRH agonists (buserelin n = 348; triptorelin n = 14, and leuprolide n = 55). The meta analysis of the data showed that pregnancy rates per embryo transfer with nafarelin were equivalent to those obtained with other GnRH agonists. Nafarelin and other agonists were also comparable in terms of several intermediate IVF outcomes, including fertilization rates, number of oocytes retrieved, peak oestradiol concentrations, and cycle cancellations. Women treated with nafarelin required fewer ampoules of human menopausal gonadotrophin (HMG)/FSH for ovarian stimulation and fewer days of stimulation. Safety results from both the meta analysis and a qualitative analysis of 12 additional reports suggested that adverse effects were within the accepted tolerance range; the most frequent adverse effects were hypo-oestrogenic symptoms. In conclusion, the overall efficacy of nafarelin was equivalent to that of other GnRH agonists. The possibility that the reduced gonadotrophin requirements in women taking nafarelin will translate into cost savings per IVF treatment cycle requires further study. PMID- 11212083 TI - Nuclear magnetic resonance (NMR) studies of homeopathic solutions. AB - The efficacy of homeopathy is controversial. Nuclear magnetic resonance (NMR) has been used to study homeopathic solutions, showing provocative results. We examined the reproducibility of one of the allegedly positive studies. 1H NMR spectra were recorded for Sulphur D4, diluted and succussed up to D30 (called potentization) at two different frequencies (300 and 500 MHz). The Sulphur solution had been potentiated according to homeopathic principles with deionized water and alcohol. Water proton T1 relaxation measurements were performed also at 20 MHz for the different potentiated Sulphur solutions. Furthermore, the homeopathic remedy Betula alba 30c (birch pollen extract) and appropriate control solution (deionized water, unsuccussed solutions and placebo globules) were measured analogously, both with frequencies giving spectra and T1 relaxometry. The Sulphur remedies showed identical one dimensional proton spectra (1H NMR) at 300 and 500 MHz, regardless of dilution/succussion stage, from D4 to D30. Furthermore, Betula 30c as a potentiated solution and its controls (ethanol dilutions and Betula diluted but not succussed) showed identical spectra. Nor were there any statistically significant differences in longitudinal (T1) relaxation times between deionized water and Sulphur D10 to D30 preparations. The shorter T1 of the Sulphur D4 preparation could be ascribed to the higher microviscosity within the sample matrix caused by the high concentration of dissolved material. Also, the T1 values of the Betula alba 30c preparation (in globular form) and control placebo globules were identical. In conclusion, published results from NMR research on homeopathy indicating differences between homeopathic solutions and control samples could not be reproduced. PMID- 11212084 TI - Nuclear magnetic resonance: let's consolidate the ground before getting excited! PMID- 11212085 TI - The efficacy and safety of a homeopathic gel in the treatment of acute low back pain: a multi-centre, randomised, double-blind comparative clinical trial. AB - Acute low back pain is a very common condition in Western industrialised countries. In most cases analgesics or topical medications are prescribed at first encounter with the general practitioner (GP). The aim of this study was to investigate whether the homeopathic gel Spiroflor SRL gel (SRL) is equally effective and better tolerated than Cremor Capsici Compositus FNA (CCC) in patients with acute low back pain. A multi-centre, randomised, double-blind, controlled clinical trial was conducted in the practices of 19 GPs in the districts of Bristol and Manchester, UK. One hundred and sixty-one subjects suffering from acute low back pain were treated for one week either with SRL or with CCC. Pain was scored on a 100 mm visual analogue scale (VAS). Main efficacy parameter VAS reduction was compared between treatments. Evaluation of safety was primarily based on the number of subjects with adverse events (AEs), withdrawals due to an AE and adverse drug reactions (ADRs). The mean difference between the VAS reduction in the SRL group and the CCC group adjusted for VAS at baseline and age was -0.6mm (90% CI = -6.5-5.3mm). Fewer subjects in the SRL group (11%) experienced an AE than in the CCC group (26%). The same applies to the number of subjects with an ADR (3/81 = 4% vs 18/74 = 24%) and the number of subjects withdrawn due to an ADR (0/81 = 0% vs 8/74 = 11%). In conclusion, SRL and CCC are equally effective in the treatment of acute low back pain, however, SRL has a better safety profile. Spiroflor SRL gel is preferable to Capsicum-based products for the topical treatment of low back pain, because of the lower risk of adverse effects. PMID- 11212086 TI - Clinical verification of symptom pictures of homeopathic medicines. AB - This invitation for co-operation is addressed to all interested groups. Its purpose is data collection for clinical verification of symptoms from homeopathic proving and collection of clinical symptoms not derived from homeopathic pathogenetic trials (provings). To date no consensus exists on this topic. The European Committee for Homoeopathy (ECH) research sub-committee has created a working group on this topic. This paper is the result of a review of papers on the topic, exchanges between members and a meeting. PMID- 11212087 TI - Cushing's disease: a new approach to therapy in equine and canine patients. AB - Forty-one cases of Cushing's Disease affecting both equine and canine patients were treated with an identical mixture of two homeopathically prepared remedies (ACTH 30c and Quercus robur 30c), and the clinical improvements seen in the cases assessed. Homeopathy has been described as a medicine that can only be prescribed on the basis of individual symptoms shown, fitting the remedy to the patient, not the disease. The aim of this study was to define whether a standardised approach, using homeopathically prepared remedies, was a valid system of therapy for this disease, and if so, whether results were repeatable between species. The overall success rate for the therapy was 80% and results were broadly similar between the two species, indicating that homeopathy lends itself to the treatment of Cushing's Disease, and also to both cohort studies and group medicine. PMID- 11212088 TI - Homeopathic remedies for the treatment of osteoarthritis: a systematic review. AB - Osteoarthritis is a common rheumatic disease. Limitations of conventional medical management of this condition indicate a real need for safe and effective treatment of osteoarthritic patients. The authors review the clinical evidence for and against the effectiveness of homeopathic medicines in the treatment of patients with osteoarthritis. A systematic review of all randomised controlled clinical trials of homeopathic treatment of patients with this condition is presented. A comprehensive search yielded four trials which are discussed in detail. The authors conclude that the small number of randomised clinical trials conducted to date, although favouring homeopathic treatment, do not allow a firm conclusion as to the effectiveness of homeopathic remedies in the treatment of patients with osteoarthritis. The clinical evidence appears promising, however, and more research into this area seems warranted. PMID- 11212089 TI - The widow spider Latrodectus tredecimguttatus: source of the remedy Tarentula hispanica? AB - The European wolf spider, Lycosa tarentula, said to have caused the historical phenomenon of 'tarantism', is the official medicinal source of the homeopathic remedy Tarentula hispanica. Yet, scientific evidence links the spider's venomous effects with mild necrotic and minor systemic effects that contrast with the proving symptoms of Tarentula hispanica which show a cerebral and neural component. A comparative investigation by use of toxicological, clinical findings, supported by modern and antique biological texts, as well as homeopathic materia medica, traces the source of the remedy Tarentula hispanica to the Mediterranean widow spider Latrodectus tredecimguttatus, thus warranting a re-evaluation of pharmacological preparation. PMID- 11212090 TI - On the investigation of homeopathic potencies using low resolution NMR T2 relaxation times: an experimental and critical survey of the work of Roland Conte et al. AB - We have attempted to reproduce differences in low resolution nuclear magnetic resonance (NMR) T2 spin-spin relaxation times between homeopathically potentised and unpotentised Nitric acid (nit-ac) solutions previously reported by Conte, et al. Using similar instrumentation and experimental protocols, we have shown that it is likely that Conte's original results are attributable to experimental artifact originating in the glassware used for the manufacture of the NMR tubes. PMID- 11212091 TI - Synthesis of 4-alkoxy-2-phenylquinoline derivatives as potent antiplatelet agents. AB - In our continuing search for novel antiplatelet agents, 4-alkoxy derivatives of 2 phenylquinoline as well as related compounds were prepared. Through biological screening, a preliminary structure antiplatelet activity relationship was established. Compounds 5-ethyl-4-methoxy-2-phenylquinoline (8), 4-ethoxy-5-ethyl 2-phenylquinoline (9), 4-ethoxycarbonylmethoxy-5-ethyl-2-phenylquinoline (10), 4 ethoxycarbonylbutoxy-5-ethyl-2-phenylquinoline (12) and 5-ethyl-4-(N ethylcarboxido)methoxy-2-phenylquinoline (17) all demonstrated potent antiplatelet activity. Among them, compound 8 was the most potent with an IC50 value of 0.08 microM and was about 3-fold more active than indomethacin. The mechanism of antiplatelet action of 8 is possibly through its inhibition on cyclooxygenase or thromboxane synthetase. PMID- 11212092 TI - Synthesis and preliminary pharmacological evaluation of coumestans with different patterns of oxygenation. AB - Five coumestans with different patterns of oxygenation in rings A and D were synthesized from resorcinol and aromatic aldehydes, and screened for their antimyotoxic activity. The most potent compound (2b, IC50 = 1 microM) was selected for study of its pharmacological profile. PMID- 11212093 TI - Potent and selective bicyclic lactam inhibitors of thrombin. Part 4: transition state inhibitors. AB - Bicyclic piperazinone based thrombin inhibitors of general structure 2 were prepared and evaluated in vitro and in vivo. These inhibitors, having in common an electrophilic basic trans-cyclohexylamine P1 residue, displayed high thrombin affinity, high selectivity against trypsin and good in vivo efficacy in the rat arterial thrombosis model. PMID- 11212094 TI - Novel cytotoxic 7-iminomethyl and 7-aminomethyl derivatives of camptothecin. AB - A series of new 7-iminomethyl derivatives of camptothecin were obtained from camptothecin-7-aldehyde and aromatic, alicyclic and aliphatic amines. Their hydrogenation led to the corresponding amines. All the imines and the less polar amines showed a marked increase of the cytotoxic activity against H460 non-small lung carcinoma cell line, with respect to topotecan. The lipophilicity of the substituent in position 7 of camptothecin seems to play an important role for cytotoxic potency. The 7-phenyliminomethyl derivative showed efficacy comparable to topotecan in vivo against NSCLC H460 xenografted in athymic nude mice. PMID- 11212095 TI - General synthesis of alpha-substituted 3-bisaryloxy propionic acid derivatives as specific MMP inhibitors. AB - Modulations of alpha and aryl substitutions on 3-aryloxy propionic acid hydroxamates led to novel and potent inhibitors of MMP-2,3,9 and 13, and selectivity versus MMP-1. PMID- 11212096 TI - Antimycobacterial in vitro activity of cobalt(II) isonicotinoylhydrazone complexes. Part 10. AB - Octahedral cobalt(II) complexes of isonicotinoylhydrazones, which were obtained from the primary antituberculous agent isoniazid, have been synthesised and characterised. Their antimycobacterial in vitro activity has been evaluated against Mycobacterium tuberculosis H37Rv: they exhibit MIC values ranging from < 0.1 to 0.39 microg/mL, showing them to be generally more active than previously reported analogous Cu(II) and Ni(II) complexes. PMID- 11212097 TI - Active site geometry of porcine pancreatic lipase: an interesting switchover from Jones' to Seebach's model. AB - Porcine pancreatic lipase (PPL)-catalyzed hydrolysis of cis 3-acetoxyethyl-1,4 diphenyl and cis 3-acetoxyethyl-1-phenyl-4-(2-furyl) beta-lactams 1a and 1b proceeded with opposite stereoselectivity while the corresponding thienyl beta lactam 1c showed no selectivity at all. An explanation based upon the dominance of hydrophobic and polar pockets in governing the stereoselectivity has been proposed. PMID- 11212098 TI - Trifluoromethyl-containing 3-alkoxymethyl- and 3-aryloxymethyl-2-pyridinones are potent inhibitors of HIV-1 non-nucleoside reverse transcriptase. AB - 3-Alkoxymethyl- and 3-aryloxymethyl-2-pyridinones were synthesized and evaluated for activity as non-nucleoside reverse transcriptase inhibitors (NNRTIs) of HIV 1. It was found that several compounds were potent inhibitors of HIV-1 with the most potent compound 24 exhibiting an IC90 = 32 nM. Compound 24 also possessed a potent resistance profile as demonstrated by submicromolar IC90s against several clinically meaningful mutant virus strains. PMID- 11212099 TI - Sulfonylated aminothiazoles as new small molecule inhibitors of protein phosphatases. AB - Based on a previously identified lead structure, SC-alphaalphadelta9, we have developed a versatile new chemical scaffold that can be readily modified to generate libraries of both Tyr and dual specificity phosphatase inhibitors with reduced molecular weight and lipophilicity. The most potent analogue identified to date, aminothiazole 8z, inhibits the dual specificity phosphatase Cdc25B with a Ki of 4.6+/-0.4 microM and a Hill coefficient of 2. PMID- 11212100 TI - The 5-HT3 antagonist tropisetron (ICS 205-930) is a potent and selective alpha7 nicotinic receptor partial agonist. AB - The 5-HT3 receptor antagonist tropisetron (ICS 205-930) was found to be a potent and selective partial agonist at alpha7 nicotinic receptors. Two other 5-HT3 receptor antagonists, ondansetron and LY-278,584, were found to lack high affinity at the alpha7 nicotinic receptor. Quinuclidine analogues (1 and 2) of tropisetron were also found to be potent and selective partial agonists at alpha7 nicotinic receptors. PMID- 11212101 TI - Stereospecific synthesis of (2S)-2-methyl-3-(2',6'-dimethyl-4'-hydroxyphenyl) propionic acid (Mdp) and its incorporation into an opioid peptide. AB - To examine the effect of replacing the N-terminal amino group in opioid peptides with a methyl group on biological activity, a stereospecific synthesis of the tyrosine analogue (2S)-2-methyl-3-(2',6'-dimethyl-4'-hydroxyphenyl)-propionic acid (Mdp) was performed. The enkephalin analogue (2S)-Mdp-D-Ala-Gly-Phe-Leu-NH2 turned out to be a quite potent delta opioid antagonist and a somewhat less potent mu antagonist, indicating that a positively charged N-terminal amino group is not a conditio sine qua non for the binding of opioid peptides to delta and mu receptors but may be required for signal transduction. PMID- 11212102 TI - Enkephalin analogues with 2',6'-dimethylphenylalanine replacing phenylalanine in position 4. AB - Four Leu-enkephalin (Enk) analogues containing 2',6'-dimethyphenylalanine (Dmp) in position 4 were prepared and tested for their receptor binding and biological activities. Among the analogues prepared, [2', 6'-dimethyltyrosine, D-Dmp4]Enk was found to be an antagonist toward mu and delta opioid receptors with pA2 values of 6.90 and 5.57, respectively. PMID- 11212103 TI - The development of a potential single photon emission computed tomography (SPECT) imaging agent for the corticotropin-releasing hormone receptor type. AB - A high-affinity radioligand for CRHR1 has been prepared that can serve as a template for the development of SPECT imaging agents. The 5-chloro-N cyclopropylmethyl-N-(2,6-dichloro-4-iodophenyl)-2-methyl-N-propylpyrimidine-4,6 diamine (6b, Ki = 14 nM), and the corresponding 4-bromophenyl analogue (6a, Ki = 21 nM), were synthesized in four steps from compound 3. PMID- 11212104 TI - Specific binding of 2-amino-1,8-naphthyridine into a single guanine bulge as evidenced by photooxidation of GG doublet. AB - Photoirradiation of 2-amino-1,8-naphthyridines in the presence of duplex DNA containing the GG doublet opposite a single bulge was examined. After hot piperidine treatment, DNA cleavage was observed preferentially at the GG opposite a single bulge. The cleavage efficiency was highly dependent on the nature of bulged base. The G cleavage at the GG opposite a single G bulge was exceptionally weak, suggesting an intercalative binding of 2-amino-1,8-naphthyridine chromophore into the GG step. PMID- 11212105 TI - Design and synthesis of tricyclic derivatives as high density lipoprotein cholesterol enhancers. AB - A pharmacophore for increasing HDLC was proposed based on common structural features of non-thio-containing compounds with HDLC enhancing properties. A search of the compound database identified various series of these non-thio containing compounds, including a novel tricyclic imidazoisoquinolone. Preparation of 1-aryl-3-oxo-1,3-dihydro-2-benzofuran-1-carboxamides using a novel and widely applicable one-step process from 2-acyl benzoic acids is reported. Reaction of diamines with 1-aryl-3-oxo-1,3-dihydro-2-benzofuran-1-carboxamides and related aza-analogues proceeded with regio-control to furnish imidazoisoquinolones, pyrimidoisoquinolones, and imidazonaphthyridines. NMR studies and X-ray crystallography confirmed the regiochemistry of the products. Compounds of these series increased concentrations of HDLC in test animals following oral administration. PMID- 11212106 TI - Selective reaction to a flipping cytidine of the duplex DNA mediated by triple helix formation. AB - A new nucleoside derivative (2) with a butyl spacer between the sugar part and the 2-amino-6-vinylpurine motif has been synthesized. The triplex-forming oligodeoxynucleotide incorporating 2 has achieved strand- and cytidine-selective cross-linking reaction to the G-C target site mediated by triple helix formation. It has been suggested that 2 reacts with a flipping cytidine at the target site. PMID- 11212107 TI - Antifungal activity of octyl gallate: structural criteria and mode of action. AB - Octyl gallate (3,4,5-trihydroxybenzoate) was found to possess antifungal activity against Saccharomyces cerevisiae and Zygosaccharomyces bailii, in addition to its potent antioxidant activity. Catechol moiety is essential to elicit this activity. The primary fungicidal activity of octyl gallate comes from its ability to act as a nonionic surface-active agent (surfactant). The length of the alkyl chain is not a major contributor but plays an important role in eliciting the activity. PMID- 11212108 TI - Anthraquinone-peptides as inhibitors of AP-1 transcription factor. AB - Peptide-1-[N-[2-succinamidylethyl]amino]anthraquinones containing five seven amino acid residues including the KCR motif important in AP-1 protein binding to DNA have been synthesised as potential transcription factor inhibitors. These anthraquinone-peptides showed DNA intercalative binding and inhibition of AP-1 protein binding to its DNA consensus sequence. PMID- 11212109 TI - The identification of alpha-ketoamides as potent inhibitors of hepatitis C virus NS3-4A proteinase. AB - Peptides based upon the non-prime side residues of the NS4A-4B cleavage site of hepatitis C virus (HCV) NS3-4A proteinase containing an alpha-ketoamide moiety in place of the scissile amide bond are potent inhibitors of this enzyme. PMID- 11212111 TI - Synthesis and photodynamic activity of a cationic zinc monoazaporphyrin bearing a nitrogen atom at the peripheral position. AB - A new cationic monoazaporphyrin, zinc 2-aza-8,12,13,17-tetraethyl-2,3,7,18 tetramethylporphyrinium iodide 3 was synthesized. Photodynamic activity of 3 in degradation of 2',3'-isopropylideneguanosine 4 was compared with 2-aza-8,12,13,17 tetraethyl-3,7,18-trimethylporphyrin 1, zinc 2-aza-8,12,13,17-tetraethyl-3,7,18 trimethylporphyrin 2, and hematoporphyrin 5. The quarternary ammonium 3 showed a remarkable increase of photodynamic activity compared with 5, although no appreciable difference in the activity was observed between 1 and 5. PMID- 11212110 TI - Conformational study of a highly specific CXCR4 inhibitor, T140, disclosing the close proximity of its intrinsic pharmacophores associated with strong anti-HIV activity. AB - We report the solution structure of T140, a truncated polyphemusin peptide analogue that efficiently inhibits infection of target cells by T-cell line tropic strains of HIV-1 through its specific binding to a chemokine receptor, CXCR4. Nuclear magnetic resonance analysis and molecular dynamic calculations revealed that T140 has a rigidly structured conformation constituted by an antiparallel beta-sheet and a type II' beta-turn. A protuberance is formed on one side of the beta-sheet by the side-chain functional groups of the three amino acid residues (L-3-(2-naphthyl)alanine, Tyr5 and Arg14), each of which is indispensable for strong anti-HIV activity. These findings provide a rationale to dissect the structural basis for the ability of this compound to block the interaction between CXCR4 and envelope glycoproteins from T-tropic strains of HIV 1. PMID- 11212112 TI - Serotonergic and dopaminergic activities of rigidified (R)-aporphine derivatives. AB - Novel rigidified (R)-aporphine derivatives were synthesized from (R)-1,11 carbonylaporphine by ring expansion reactions. The structures of the novel analogues were assigned by NMR spectroscopy and X-ray crystallography. The compounds showed moderate affinities and selectivities at serotonin S-HT1A and 5 HT7 and dopamine D2A receptors. PMID- 11212113 TI - Securiosides A and B, novel acylated triterpene bisdesmosides with selective cytotoxic activity against M-CSF-stimulated macrophages. AB - We report the discovery of securiosides A (1) and B (2), novel acylated triterpene bisdesmosides, isolated from the roots of Securidaca inappendiculata. Securiosides A and B showed potent selective cytotoxic activity against M-CSF stimulated macrophages and were suggested to have potential as new agents for the treatment of inflammatory diseases such as RA and atherosclerosis. PMID- 11212114 TI - Synthesis and biological activity of novel potent endothelin-converting enzyme-1 inhibitors. AB - Through directed screening of metalloprotease inhibitors, CGS 30084 (1) has been identified as a potent endothelin-converting enzyme-1 (ECE-1) inhibitor in vitro (IC50 = 77 nM). Herein we report the syntheses and biological activities of analogues derived from this lead, based on modifications of the biphenyl moiety. Compound 10, the thioacetate methyl ester prodrug derivative of compound 6m, was found to be an orally active and potent inhibitor of ECE-1 activity in rats. PMID- 11212115 TI - Human beta3 adrenergic receptor agonists containing cyanoguanidine and nitroethylenediamine moieties. AB - Pyridineethanolamine derivatives containing cyanoguanidine or nitroethylenediamine moieties were examined as human beta3 adrenergic receptor (AR) agonists. Notably, indoline derivatives 6a and 11 were potent beta3 AR agonists (beta3 EC50 = 13 and 19 nM, respectively), which showed good selectivity over binding to and minimal activation of the beta1 and beta2 ARs. PMID- 11212116 TI - Solid-phase synthesis of oligonucleotides containing a bipyridine ligand at the 3'-3' inversion of polarity site. AB - The preparation of a solid support useful for the synthesis of oligonucleotides with a 3'-3' inversion of polarity, via a linker containing a chelating molecule, namely 2,2'-bipyridine, is described. PMID- 11212117 TI - Solid-phase synthesis of pyrrolo[2,1-c][1,4]benzodiazepine-5,11-diones. AB - The solid-phase synthesis of biologically important pyrrolo[2,1 c][1,4]benzodiazepine-5,11-diones using Wang resin through amide formation and reductive cyclization procedures is described. Further, N10-substituents have been introduced in the final products and these have been cleaved from the solid support in good yields. PMID- 11212118 TI - Bicyclic nucleoside inhibitors of Varicella-Zoster Virus (VZV): the effect of terminal unsaturation in the side chain. AB - Novel bicyclic nucleoside analogues bearing long alkyl side chains are prepared and tested as inhibitors of VZV. In particular, analogues with terminal unsaturation in the side chain are reported. Whilst terminal alkenyl derivatives are potent antivirals, the corresponding terminal alkynyls are poorly active. PMID- 11212119 TI - Synthesis and antifungal activities of novel 1,3-beta-D-glucan synthase inhibitors. Part 1. AB - Highly potent 1,3-beta-D-glucan synthase inhibitors 10, 11 and 13 have been identified by the chemical modification of the fungicidal macrocyclic lipopeptidolactone, RO-09-3655 (1), isolated from the cultured broth of Deuteromycotinia spp. D-Ornithine derivative (10) showed improved antifungal activity in the systemic candidiasis model in mice and reduced hepatotoxicity in vitro, as compared with 1. PMID- 11212120 TI - FR131535, a novel water-soluble echinocandin-like lipopeptide: synthesis and biological properties. AB - The synthesis and biological properties of a novel water-soluble echinocandin like lipopeptide, FR131535, are described. This compound displayed potent in vitro and in vivo antifungal activities. The hemolytic activity of FR901379 was reduced by replacing the acyl side chain. This compound showed good water solubility, comparable to the natural product FR901379. PMID- 11212121 TI - Anti-Helicobacter pylori agents endowed with H2-antagonist properties. AB - New anti-Helicobacter pylori (H. pylori) agents endowed with H2-antagonists properties were obtained by combining the lamtidine derived pharmacophoric group with the antibiotic calvatic acid. All the compounds were tested for their irreversible H2-antagonist properties and for their ability to inhibit 20 H. pylori strains, two of them metronidazole resistant. The most active derivative (compound 4) displayed antimicrobial activity similar to metronidazole. PMID- 11212122 TI - Orally active docetaxel analogue: synthesis of 10-deoxy-10-C-morpholinoethyl docetaxel analogues. AB - To improve cytotoxicity of 10-deoxy-10-C-morpholinoethyl docetaxel analogues against various tumor cell lines including resistant cells expressing P glycoprotein (P-gp), we modified the 7-hydroxyl group to hydrophobic groups (methoxy, deoxy, 6,7-olefin, alpha-F, 7-beta-8-beta-methano, fluoromethoxy). Among these analogues, the 7-methoxy analogue showed the strongest cytotoxicity. This analogue showed potent activity against B16 melanoma BL6 in vivo by oral administration. PMID- 11212123 TI - A model of photoprobe docking with beta1,4-galactosyltransferase identifies a possible carboxylate involved in glycosylation steps. AB - A molecular docking study has been performed on the interaction of beta1,4 galactosyltransferase with an acceptor site photoprobe. This is based on an acceptor site peptide fragment which was recently identified by the use of a photoprobe. The present model strongly suggests that the carboxylate group of Asp318 could be involved in the activation of the acceptor sugar 4-OH for the efficient galactosyltransfer. The result also exemplified that the combination of photoaffinity labeling with crystallography is a powerful method for the detailed structural analysis of ligand protein complex. PMID- 11212124 TI - Nipecotic and iso-nipecotic amides as potent and selective somatostatin subtype-2 receptor agonists. AB - N-Substituted nipecotic and iso-nipecotic amides of beta-methylTrpLys tert-butyl ester were found to be novel, selective and potent agonists of the somatostatin subtype-2 receptor in vitro. For example iso-nipecotic amide 8a showed high hsst2 binding affinity (Ki = 0.5 nM) and good selectivity (h5/h2 = 832). PMID- 11212125 TI - Synthesis and transfecting properties of a glycosylated polycationic DNA vector. AB - A glycosylated analogue of dialkylamidoglycylcarboxyspermine was synthesized. The physico-chemical and transfecting properties of 11 were evaluated indicating that this cationic lipid forms stable particles at low charge ratio and is efficient for gene delivery. PMID- 11212126 TI - Structure-activity relationships of novel anti-malarial agents. Part 2: cinnamic acid derivatives. AB - We have described compound 1 as a lead structure for a novel class of anti malarial agents. Replacement of the 3-phenylpropionyl moiety of the lead structure 1 by a 4-propoxycinnamic acid residue resulted in a significant improvement in antimalarial activity. Compound 3q represents an important step in the development of lead structure 1 into an anti-malarial drug candidate. PMID- 11212127 TI - Non-peptidic, non-prenylic inhibitors of the prenyl protein-specific protease Rce1. AB - Several compounds designed as bisubstrate analogues of protein farnesyltransferase inhibited the prenyl protein-specific protease Rce1, qualifying them as lead structures for a novel class of non-peptidic, non prenylic inhibitors of this protease. PMID- 11212128 TI - Cytotoxic Michael-type amine adducts of alpha-methylene lactones alantolactone and isoalantolactone. AB - Two series of cytotoxic (IC50, K562 cell line, 1-24 microM) alpha-aminomethyl substituted lactones 3 and 4 were prepared by stereoselective Michael-type addition of amines to alantolactone (1) and isoalantolactone (2). The lactones 1 and 2 and their amine adducts induce apoptosis and act as alkylating agents. PMID- 11212129 TI - Equilibrium and kinetics studies of transnitrosation between S-nitrosothiols and thiols. AB - Using UV-vis spectrometrical measurements, equilibrium constants for NO transfer between S-nitroso-N-acetyl-penicillamine (SNAP) and different thiols as well as kinetic data for NO transfer from S-nitroso bovine serum albumin (BSANO) to thiols have been obtained. NO transfer from SNAP to other primary/secondary thiols are thermodynamically favorable, whereas other S-nitrosothiols exhibit similar NO transfer potential. The obtained Gibbs free energy, enthalpy and entropy data indicated that NO transfer reactions from SNAP to four thiols are exothermic with entropy loss. The kinetic behavior of BSANO/RSH transfer can be related to both the acidity of sulfhydryl group and the electronic structure in thiol. PMID- 11212131 TI - Relationship between brain atrophy and disability: an 8-year follow-up study of multiple sclerosis patients. AB - Brain atrophy measurement can provide an estimate of the amount of tissue destruction due to the pathologic processes in multiple sclerosis. The potential usefulness of atrophy as a marker of disease progression depends upon the concurrent and predictive relationships between atrophy and disability. A follow up study was performed to measure atrophy and disability scores in patients from the Multiple Sclerosis Collaborative Research Group's phase III trial of IFNbeta 1a (Avonex) in relapsing- remitting multiple sclerosis. New data were obtained on 160 out of 172 eligible patients from the original trial were enrolled in the follow-up study approximately 8 years after randomization. The follow-up visit consisted of several tests and questionnaires including a clinical exam to determine Expanded Disability Status Score (EDSS) and Multiple Sclerosis Functional Composite (MSFC), and a magnetic resonance imaging exam to calculate the brain parenchymal fraction. Brain parenchymal fraction was correlated with both EDSS and MSFC at each of the four time points for which data were available (baseline 1, 2 and 8 years). Furthermore, the change in BPF was correlated with the changes in disability scores from the end of the phase III trial to the follow-up exam. These data suggest that brain atrophy may be a useful and clinically relevant marker of disease progression in relapsing--remitting MS. PMID- 11212130 TI - Brain atrophy in relapsing multiple sclerosis: relationship to relapses, EDSS, and treatment with interferon beta-1a. AB - Brain atrophy is a relevant surrogate marker of the disease process in multiple sclerosis (MS) because it represents the net effect of various pathological processes leading to brain tissue loss. There are various approaches to quantifying central nervous system atrophy in MS. We have focused on a normalized measure of whole brain atrophy, the brain parenchymal fraction (BPF). BPF is defined as the brain parenchymal volume, divided by the volume within the surface of the brain. We applied this method to an MRI data set generated during a phase III clinical trial of interferon beta-1a (AVONEX). The purpose of the current study is to further explore clinical and MRI correlates of the BPF, particularly as they relate to relapse rate and Kurtzke's Expanded Disability Status Score (EDSS); and to further explore the therapeutic effects observed in interferon beta-1a recipients. Of all demographic and disease measures in the clinical trial data base, T2 lesion volume most closely correlated with BPF in cross sectional studies, and was the baseline factor most closely correlated with progressive brain atrophy in the subsequent 2 years. We also observed that change in T2 lesion volume was the disease measure most closely correlated with change in BPF during 2 years of observation. Of interest, relapse number and EDSS change during 2 years were only weakly correlated with BPF change during the same period. Disability progression, defined as sustained worsening of at least 1.0 EDSS points from baseline, persisting at least 6 months, was associated with significantly greater brain atrophy progression. We observed a therapeutic effect of interferon beta-1a in the second year of the clinical trial, and this beneficial effect was not accounted for by change in gadolinium enhanced lesion volume, or by corticosteroid medication within 40 days of the final MRI scan. The BPF is an informative surrogate marker for destructive pathological processes in relaping MS patients, and is useful in demonstrating treatment effects in controlled clinical trials. The significance of progressive brain atrophy during relapsing MS will be assessed by measuring clinical and MRI changes in prospective follow up studies. PMID- 11212132 TI - Increase in serum levels of uric acid, an endogenous antioxidant, under treatment with glatiramer acetate for multiple sclerosis. AB - Free radicals including peroxynitrite are induced in Multiple Sclerosis (MS). Antioxidant and peroxynitrite inhibitor uric acid (UA), suppresses the MS animal model experimental autoimmune encephalomyelitis (EAE). MS patients have lower average serum UA than controls. An inverse relationship exists between MS and gout Glatiramer acetate (GA) suppresses EAE and is beneficial in relapsing MS. We investigated serum UA changes during open-label treatment of relapsing MS with GAA. Ten patients (six females, four males, aged 19 to 39 years, mean age 32 years) completed 6 months of GAA (Copaxone 20 mg s.c daily). Of these, nine completed 12 months. After 6 months on GAA, serum UA (normal, 173359 micromol/ml for women, 258-491 micromol/ml for men) increased in nine and marginally decreased (302 to 300 micromol/ml) in a single patient. Mean UA significantly increased from 240 to 303 micromol/ml (P=0.0014). At 12 months, UA remained significantly higher than at start (P=0.006) decreasing in only one patient. In contrast, we found no significant UA changes after 6 and 12 months of treatment in 21 MS patients treated with interferon beta1-a (Avonex), or in 11 treated with interferon beta1-a (Rebif), or in five placebo-treated controls. Increasing UA, a natural inhibitor of free radicals, may represent a mechanism of action of glatiramer acetate in MS. PMID- 11212133 TI - Self-reported visual dysfunction in multiple sclerosis: results from the 25-Item National Eye Institute Visual Function Questionnaire (VFQ-25). AB - Visual impairment is one of the most common clinical manifestations of Multiple Sclerosis (MS), and is strongly related to overall health-related quality of life (HRQOL) in MS and other disorders. However, the assessment of vision-specific HRQOL in patients with MS has been limited. The purpose of this study was to examine self-reported visual dysfunction in a clinically heterogeneous MS cohort using the 25-Item National Eye Institute Visual Function Questionnaire (VFQ-25). The VFQ-25 was administered by telephone interview to a subset of participants in a follow-up study to a phase III trial of interferon beta-1a for relapsing remitting MS. Mean VFQ-25 composite scores and selected sub-scale scores were significantly lower (worse) among patients in our MS cohort (n=35) compared with a published reference group of patients with no history of chronic eye disease (n= 118). These differences were observed despite a relatively younger age and tighter distribution of binocular visual acuities in the MS cohort Patients with MS in this study thus demonstrated a greater degree of self-reported visual dysfunction, as measured by the VFQ-25, compared with an eye disease-free reference group. The VFQ-25 is a potentially useful measure of vision-specific HRQOL in patients with MS. PMID- 11212134 TI - Olfactory dysfunction and extent of white matter abnormalities in multiple sclerosis: a clinical and MR study. AB - BACKGROUND: The relative contribution to the olfactory dysfunction of the lesions in the specific brain regions involved in olfaction compared with the lesions scattered all over the rest of the brain has not been fully clarified yet in patients with multiple sclerosis (MS). The concurrent use of Magnetic Resonance Imaging (MRI) and a standardized test of odor identification ability now permits to study the relation between smell loss and the extent of white matter abnormalities. METHODS: We tested the olfactory function of 40 patients with definite MS and of 40 age-sex- and smoking-habit-matched healthy controls by using the Cross Cultural Smell Identification Test. We measured also the lesion load on T2-weighted images in the inferior-frontal and temporal lobes and in the rest of the brain in MS patients. Therefore, we tried to correlate measures of lesion load and smell test scores. RESULTS: A robust correlation was demonstrated between MR measures of lesion load in the white matter of the olfactory brain region and smell loss (r=-0. 739, P<0.0001). A significant relationship has been found even after taking potential confounding factors, such as sex, age, disease duration, disability, anxiety and depression, into account (r=-0.90, P<0.0001). CONCLUSIONS: Our findings show, in MS patients with stable neurological impairment and no recent disease exacerbation, a correlation between smell loss and the lesion load in the regions of the brain involved in olfaction and support the theory that the extent and severity of MRI abnormalities in specific brain regions are related to the presence of selective neurologic and neuropsychologic impairment. PMID- 11212135 TI - Neuropsychological counseling improves social behavior in cognitively-impaired multiple sclerosis patients. AB - We studied the effectiveness of a newly-developed cognitive-behavioral intervention in 15 patients with marked cognitive impairment and behavior disorder. The design was a single-blind test of a neuropsychological intervention, with pre- and post-treatment assessments of personality and social behavior. MS patients underwent neurological examination and neuropsychological testing at baseline. The patients were then randomly assigned to neuropsychological counseling or standard, non-specific supportive psychotherapy. The active 12-week treatment emphasized enhancement of insight through education, social skills training, and behavior modification. All patients were re-examined within 2 weeks of the termination of treatment. Neuropsychological technicians were blind to treatment condition. Both groups showed evidence of cognitive impairment and personality/behavior disorder prior to treatment and were well matched on demographic, disability, and cognitive measures. Patients who underwent neuropsychological counseling showed significant positive response on measures of social behavior (e.g. excessive ego-centric speech) compared to those who underwent standard counseling. We conclude that these data support the use of non-pharmacological, neuropsychological counseling in patients with acquired, MS associated behavior disorder. PMID- 11212136 TI - Personality as a predictor of coping efforts in patients with multiple sclerosis. AB - The aim of the study was to explore personality traits as predictors of coping with disease-related distress in patients with multiple sclerosis (MS). All patients with clinically definite MS in a city with a population of approximately 100000 were asked to complete the NEO Personality Inventory and a multidimensional coping inventory (COPE). There was an 83% response rate yielding 49 patients for the study population and 49 controls, matched for age, gender and educational level to the MS-patients, were used as comparison. Only Neuroticism correlated significantly with emotion-focused coping in both groups. Extraversion and Openness to Experience were linked to task-oriented coping strategies in normal controls but not in the MS-group. Agreeableness was associated with avoidance-oriented coping strategies only in the MS-group. Thus, the relation of certain personality characteristics to the choice of strategies for coping with the disease-related distress appear to differ from coping with stressful problems in everyday life. As dispositional characteristics may interfere with adaptive coping responses, analysis of personality traits and coping strategies could contribute while attempting to relieve the consequences of chronic disease on everyday life. PMID- 11212137 TI - Neurological worsening due to infection from renal stones in a multiple sclerosis patient. AB - Symptomatic bladder dysfunction occurs in the majority of patients with multiple sclerosis (MS). Although guidelines have been established for diagnosis and management of bladder dysfunction in these patients, they are sometimes overlooked in the primary care setting, leading to severe, life threatening complications. A 64-year-old male with a 31-year history of spastic quadriparetic MS and neurogenic bladder dysfunction managed with an indwelling catheter, presented to the hospital with worsening neurological function. He had developed increased weakness and cognitive impairment several weeks after being treated for a urinary tract infection (UTI). He had become unable to perform any activities of daily living or drive his power wheelchair. After an extensive work-up, he was found to have a large (14 x 18 x 30 cm) retroperitoneal abscess and multiple renal stones, including a large obstructing calculus in the collecting system near the ureteropelvic junction, and he underwent nephrectomy and abscess drainage. Of note, he had been found to have multiple renal stones and hydronephrosis on renal ultrasound 3 years earlier, but he had received no treatment. Following drainage of the abscess, his upper extremity neurological function returned to baseline, his cognitive status improved, and he regained the ability to perform activities of daily living. Patients with paralysis from MS, much like those with traumatic spinal cord injuries, are at grave risk of mortality and morbidity from undiagnosed and under-treated urinary complications. This case demonstrates that evaluation and appropriate treatment for complications of neurogenic bladder should be part of routine care for patients with MS. Current recommendations for evaluation and management of bladder dysfunction in patients with MS will be reviewed. PMID- 11212139 TI - Establishment of two new Orthopteran cell lines. PMID- 11212138 TI - A novel in vitro model of tumor angiogenesis. PMID- 11212140 TI - Symmetry breaking in cultured mammalian cells. PMID- 11212141 TI - Establishment of a human hepatoma cell line, HLE/2E1, suitable for detection of p450 2E1-related cytotoxicity. AB - By transfection of an expression vector of human cytochrome P450 2E1 (CYP2E1) into a human hepatoma cell line (HLE), a new cell line (HLE/2E1) that stably expresses activity of CYP2E1 has been established. The HLE/2E1 cell line expressed a higher level of CYP2E1 messenger ribonucleic acid than did the mother HLE cell line. CYP2E1 enzyme activity determined by a p-nitrophenol oxidation assay was also higher in HLE/2E1 cells than in HLE cells. In addition, the enzyme activity of the HLE/2E1 cells was increased by ethanol treatment. Exposure to acetaminophen (APAP) or buthionine sulfoximine (BSO) caused a greater decrease in viability of the HLE/2E1 cells than that of the HLE cells, as determined by the 3 [4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. The cytotoxicity of APAP or BSO to HLE/2EI cells was inhibited by the addition of ethanol or vitamin E. However, the cytotoxicity of both APAP and BSO was enhanced by 24-h preincubation of HLE/2E1 cells with ethanol. These results show that this cell line provides a useful model for studying catalytic properties of CYP2E1 and cytotoxic mechanisms of chemicals metabolized by CYP2E1. PMID- 11212142 TI - Novel cell culture medium for use in oxidation experiments provides insights into mechanisms of endothelial cell-mediated oxidation of LDL. AB - Though one prominent theory of atherogenesis involves free-radical oxidation of low-density lipoprotein (LDL) within the vessel wall by one of the vascular cell types, the mechanism for cell-mediated LDL oxidation remains unclear[sn1]. In these studies we examined the effects of media phenols, thiols, and metals on endothelial cell-mediated oxidation. We found that cell culture media such as Dulbecco modified Eagle medium and minimal essential medium are unable to support cell-mediated oxidation of LDL because they contain high concentrations of phenol red (PR) and tyrosine, both of which strongly inhibit cell-mediated oxidation. Ham's F-10, a commonly used medium for cell-mediated oxidation experiments, is also not entirely appropriate, as it contains both PR and cysteine. Cysteine is not critical for endothelial cell-mediated oxidation, but does increase oxidation of LDL in the absence of cells. Finally, of utmost importance to cell-mediated oxidation was the presence of either micromolar concentrations of Fe(II) or physiological concentrations of holo-ceruloplasmin, the protein which carries copper in plasma. An appropriate culture medium for use in cell-mediated oxidation experiments should thus contain either micromolar concentrations of Fe(II) or physiological concentrations of holo-ceruloplasmin, and should be prepared without PR, cysteine, or large concentrations of tyrosine, all of which are shown here to inhibit endothelial cell-mediated LDL oxidation. These results are consistent with a mechanism of cell-mediated oxidation involving Fenton-type chemistry and redox cycling of the metal. PMID- 11212144 TI - Roles of beta-catenin in somitogenesis in rat embryos. AB - We studied the roles of beta-catenin in somitogenesis using immunostaining and antisense experiments in rat embryos. High levels of beta-catenin appeared transiently in the developing rat somites. Initially, beta-catenin accumulation was observed in the core cells of presomitic cell aggregates and then in the lumen of epithelial vesicles. Subsequently, it was confined to the dermomyotomes and their lumen and then the myotomes. High levels of cyclin D1 were observed in the core cells, in the lumen of epithelial vesicles, in myotomes, and in mesenchymal sclerotomes. When embryos were cultured in medium supplemented with beta-catenin antisense oligodeoxynucleotide (ODN), the accumulation of beta catenin, but not of cyclin D1, in the nascent somites and dermomyotomes was suppressed, while the number of somites was the same as that observed in control embryos. The number of myosin-positive somites and the amount of myosin per somite in embryos treated with the antisense ODN were lower than those in controls. These results suggested that beta-catenin promotes development of myotomal cells during somitogenesis. The function of beta-catenin in the development of myotomes may not be correlated to cyclin D1. PMID- 11212143 TI - Mammary fibroblasts stimulate growth, alveolar morphogenesis, and functional differentiation of normal rat mammary epithelial cells. AB - Stromal-epithelial interactions play a profound role in regulating normal and tumor development in the mammary gland. The molecular details of these events, however, are incompletely understood. A novel serum-free transwell coculture system was developed to study the natural paracrine interactions between mammary epithelial cells (MEC) and mammary fibroblasts (MFC) isolated from normal rats during puberty. The MEC were cultured within a reconstituted basement membrane (RBM) in transwell inserts with or without MFC in the lower well. The presence of MFC stimulated epithelial cell growth, induced alveolar morphogenesis, and enhanced casein accumulation, a marker of the functional differentiation of MEC, but did not induce ductal morphogenesis. Potent mitogenic, morphogenic, and lactogenic effects were observed when the MFC were cultured either on plastic or within a layer of RBM. Although most MFC maintained on plastic died after 1 wk in serum-free medium, fibroblast survival was enhanced significantly when the MFC were cultured within the RBM. Taken together, this in vitro model effectively reconstitutes a physiologically relevant three-dimensional microenvironment for MEC and MFC, and seems ideal for studying the locally derived factors that regulate the developmental fate of the epithelial and fibroblast compartments of the mammary gland. PMID- 11212145 TI - Effects of collagen gel configuration on behavior of vascular smooth muscle cells in vitro: association with vascular morphogenesis. AB - The growth, behavior, and contractile protein expression of rabbit aortic smooth muscle cells (SMC) grown on, between layers, or within a collagen gel was investigated by confocal laser scanning fluorescence microscopy and Western analysis. SMC grown on collagen gel behaved similarly to those on conventional culture dishes. However, when a second layer of collagen was overlaid, cells underwent an elongated quiescent phase before onset of proliferation and a more than threefold lower logarithmic growth rate was observed. These cells self organized into a network with ring-like structures. With increasing culture time, some of the rings developed into funnel-like, incomplete or complete tubular structures. If a tubular template preexisted within the gel, the SMC established a cylinder-shaped tube with several circularly arranged muscular layers (similar to an artery wall). This behavior mimicked endothelial cells during angiogenesis in vitro. A similar phenomenon occurred in cultures in which SMC were randomly mixed in a collagen gel, but here their behavior and morphology varied with their position within the gel. Western blot analysis showed that the SMC differentiation marker, smooth muscle myosin heavy chain-2 (SM-2), rapidly decreased, disappearing by day 10 in SMC grown on collagen, but was still detectable until day 25 in cells cultured between or within the same gel. These findings indicate that like endothelial cells, vascular SMC can display blood vessel formation behavior in vitro when an appropriate three-dimensional matrix environment is provided to keep them in a relatively higher-differentiated and low-proliferative state. PMID- 11212146 TI - Comparative in vitro cytotoxicity of ethyl acrylate and tripropylene glycol diacrylate to normal human skin and lung cells. AB - The potential for occupational exposure to the esters of acrylic acid (acrylates) is considerable, and, thus, requires a greater understanding of the their toxicity. Confluent (70-90%) cultures of normal human epidermal keratinocytes (NHEK), dermal fibroblasts (NHDF). or bronchial epithelium (NHBE) were exposed to the monofunctional ethyl acrylate (EA), the multifunctional tripropylene glycol diacrylate (TPGDA), or TPGDA monomer in a radiation curable lacquer (Lacquer A) at equimolar dosages in order to determine human in vitro cytotoxicity. Viability of the cells after 2-24-h exposure to the representative monofunctional or multifunctional acrylate or solvent control was used to calculate an index of acute cytotoxicity (50% inhibitory dose; ID50) and to determine the shape of the dose-response curves. TPGDA, Lacquer A, and EA were equally cytotoxic (ID50 is approximately equal to 0.1 micromol/cm2) to NHEK at equimolar doses. TPGDA or Lacquer A were more cytotoxic (is approximately equal to 100X) to NHDF or NHBE than EA. Sequential exposure of UV(A) and TPGDA to NHEK indicate the potential for a synergistic cytotoxic response. These findings are consistent with observed decreases in free sulfhydryl groups (e.g., glutathione or cysteine) that parallel the dose-response-related decreases in viability. logether, these data suggest possible differences in toxicity between the monofunctional EA and multifunctional TPGDA to NHEK, NHDF. or NHBE, possibly due to the difference in the number of functional acrylate groups and/or physicochemical differences (e.g., vapor pressure) between the acrylates investigated. PMID- 11212147 TI - Comparison of differentiated dendritic cell infiltration of autoimmune and osteoarthritis synovial tissue. AB - OBJECTIVE: Infiltration of rheumatoid arthritis (RA) synovial tissue (ST) by differentiated dendritic cells (DC) is a consistent feature in patients with active disease. However, mononuclear cells (MNC), including DC, may be nonspecifically chemoattracted to inflammatory sites regardless of etiology. Therefore, to evaluate the specificity of ST infiltration by differentiated DC, synovial biopsies from patients with RA, spondylarthropathy (SpA), osteoarthritis (OA), and gout were examined. METHODS: Formalin-fixed ST sections were analyzed by double immunohistochemical staining for vascularity and infiltration by differentiated DC, lymphocytes, and macrophages. RESULTS: DC containing nuclear RelB were found in perivascular MNC aggregates from patients with all arthritides studied. Infiltration by differentiated DC was similar in RA and SpA ST, but reduced in OA ST. Differentiated DC were always observed in close association with lymphocytes, and the correlation between these variables suggested that the infiltration of inflammatory sites by DC and lymphocytes was associated. CONCLUSION: Perivascular infiltration by DC, lymphocytes, and macrophages is nonspecifically related to inflammation, but signals present in RA and SpA ST lead to more intense cellular infiltration and accumulation. PMID- 11212149 TI - Early degradation of type IX and type II collagen with the onset of experimental inflammatory arthritis. AB - OBJECTIVE: To determine whether following the onset of intraarticular inflammation, there is early damage to articular cartilage, specifically to types II and IX collagen, and the proteoglycan (PG) aggrecan, and whether measurement of the degradation products of these molecules in synovial fluid (SF) and serum may permit the detection of cartilage damage. METHODS: A rabbit model of rheumatoid arthritis, antigen (ovalbumin)-induced arthritis, was studied. Articular cartilage samples were analyzed by immunoassays for total type II collagen content, its denaturation and cleavage by collagenases, and for type IX collagen content. PG content was determined by colorimetric assay. In serum and SF, total PG content and collagenase-generated peptides of type II collagen were measured. RESULTS: After 6 days, both the PG content and the NC4 domain of type IX collagen were reduced in femoral and tibial cartilage, concomitant with the onset of arthritis. In only the tibial cartilage did this reduction in PG persist up to day 20. However, denatured type II collagen was increased in all cartilage samples, but only on day 20. In SF, the PG content was significantly reduced on day 20, and products of type II collagen cleavage by collagenase were significantly increased on both day 6 and day 20. CONCLUSION: This study, which is the first of its kind examining changes in both types II and IX collagen and PG content, reveals early damage to both types of collagen as well as to PG in articular cartilage samples following induction of joint inflammation. SF analyses reveal this early damage and may be of value in the study and treatment of inflammatory arthritic diseases such as rheumatoid arthritis. PMID- 11212148 TI - Dependence of interleukin-1-induced arthritis on granulocyte-macrophage colony stimulating factor. AB - OBJECTIVE: To determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage CSF (M-CSF or CSF-1) are involved in the methylated bovine serum albumin/interleukin-1 (mBSA/IL-1)-induced arthritis model. METHODS: Following systemic injection, IL-1 has been shown to augment a weak inflammatory response to mBSA in murine joints and to induce an acute erosive arthritis. GM CSF and M-CSF have been implicated in inflammatory reactions, including those in joints, and have recently been shown to exacerbate murine arthritis. Since in vitro studies have found that IL-1 can enhance GM-CSF and M-CSF production, we reasoned that they might be playing a part in IL-1-mediated arthritis. GM-CSF deficient (GM-CSF-/-) and M-CSF-deficient (op/op) mice were injected intraarticularly with mBSA and subcutaneously with IL-1. Arthritis was monitored histologically on day 7. Normal mice were also treated intraperitoneally with blocking monoclonal antibodies to GM-CSF and M-CSF, and to the M-CSF receptor. Numbers of macrophages (Mac-2 and F4/80 staining) were monitored, as was the number of cycling (bromodeoxyuridine-positive) cells. RESULTS: GM-CSF-/- mice and normal mice treated with anti-GM-CSF antibody did not show IL-1-induced arthritis progression. There was a dramatic reduction in synovial cellularity, including reduced numbers of macrophages and cycling cells. The op/op mice did not develop mBSA/IL-1-induced disease, but blocking antibody to M-CSF or to the M-CSF receptor failed to diminish disease in normal mice. CONCLUSION: GM-CSF is involved in the IL-1-induced arthritis that follows mBSA injection; M-CSF involvement in the model is also suggested, since op/op mice did not develop arthritis. These studies provide the first in vivo evidence for a role of GM-CSF, and possibly M-CSF, in the proinflammatory actions of IL-1. PMID- 11212150 TI - Disease-modifying activity of SB 273005, an orally active, nonpeptide alphavbeta3 (vitronectin receptor) antagonist, in rat adjuvant-induced arthritis. AB - OBJECTIVE: To evaluate the effects of SB 273005, a potent, orally active nonpeptide antagonist of the integrin avbeta3 vitronectin receptor, on joint integrity in rats with adjuvant-induced arthritis (AIA). METHODS: Male Lewis rats with AIA were orally dosed either prophylactically (days 0-20) or therapeutically (days 10-20) with SB 273005. Efficacy was determined by measurement of paw inflammation, assessment of bone mineral density using dual-energy x-ray absorptiometry (DEXA), magnetic resonance imaging (MRI), and histologic evaluation. RESULTS: SB 273005 is a potent antagonist of the closely related integrins, avbeta3 (Ki = 1.2 nM) and alphavbeta5 (Ki = 0.3 nM). When SB 273005 was administered prophylactically to AIA rats twice per day, it inhibited paw edema at doses of 10, 30, and 60 mg/kg, by 40%, 50%, and 52%, respectively. Therapeutic administration twice daily was also effective, and a reduction in paw edema was observed at 30 mg/kg and 60 mg/kg of the antagonist (by 36% and 48%, respectively). SB 273005 was also effective when administered once per day, both prophylactically and therapeutically. Significant improvement in joint integrity in treated rats was shown using DEXA and MRI analyses. These findings were confirmed histologically, and significant protection of bone, cartilage, and soft tissue was observed within the joint. CONCLUSION: Symptoms of AIA in rats were significantly reduced by either prophylactic or therapeutic treatment with the alphavbeta3 antagonist, SB 273005. Measurements of paw inflammation and of bone, cartilage, and soft tissue structure indicated that this compound exerts a protective effect on joint integrity and thus appears to have disease-modifying properties. PMID- 11212151 TI - CD4+,CD28- T cells in rheumatoid arthritis patients combine features of the innate and adaptive immune systems. AB - OBJECTIVE: To determine whether CD4+,CD28- T cells, which are expanded in patients with rheumatoid arthritis (RA), express receptors that typically regulate the function of natural killer (NK) cells. METHODS: Expression of the NK cell surface molecules CD158, p70, CD94, CD161, and CD8alpha on T cell subsets was determined by multicolor flow cytometric analysis of peripheral blood mononuclear cells from 36 RA patients. Expression of CD161 on tissue-infiltrating CD4 T cells was determined by 2-color immunohistochemistry analysis of synovial tissue samples. RESULTS: Killer cell-inhibitory receptors (KIR) and killer cell activating receptors (KAR) were exclusively expressed on CD4+,CD28- T cells, with the CD158b molecule being the most frequently detected isoform. A coordinated mechanism inducing KIR/KAR expression was suggested by similarities in the expression of CD158b on CD4 and CD8 T cells. CD4+,CD28- T cells were also positive for CD8-alphaalpha homodimers, another characteristic shared with NK cells. Of the C-type lectin NK cell receptors (NK receptors), CD94 was consistently absent, but CD161 was found on a CD4 T cell population that is significantly expanded in RA patients (P = 0.01). Involvement in disease of NK receptor-expressing CD4 T cells was suggested by the presence of CD4+,CD161+ T cells in follicular microstructures typical of rheumatoid synovitis. CONCLUSION: Patients with RA have an expanded and unusual subset of CD4 T cells that infiltrates the tissue lesions and is characterized by a deficiency of CD28, the expression of CD8-alphaalpha homodimers, and the expression of several types of HLA class I-recognizing NK receptors. CD4 T cells bearing NK receptors can bridge functions of the innate and adaptive immune systems, such as responsiveness to specific antigen, rapid release of interferon-gamma, cytotoxicity, independence from classic costimulatory pathways, and integration of multiple activating and inhibitory signals to control effector functions. PMID- 11212152 TI - Induction of endothelial cell decay-accelerating factor by vascular endothelial growth factor: a mechanism for cytoprotection against complement-mediated injury during inflammatory angiogenesis. AB - OBJECTIVE: Decay-accelerating factor (DAF) is a widely expressed, multifunctional cell surface protein involved in complement regulation and cell signaling. Previous studies have demonstrated that endothelial cell (EC) DAF is up-regulated by tumor necrosis factor alpha and inhibits complement binding. Because vascular endothelial growth factor (VEGF) is cytoprotective to endothelium and is expressed at sites of chronic inflammation, we hypothesized that VEGF may induce DAF expression during inflammatory angiogenesis. METHODS: Human umbilical vein and dermal microvascular EC were isolated using routine procedures, and the regulation and function of DAF, as well as other complement-regulatory proteins (membrane cofactor protein and CD59), were analyzed following stimulation with VEGF. RESULTS: Incubation of large- or small-vessel EC with VEGF led to increased expression of DAF, with maximal expression after 48-72 hours of stimulation. This effect depended on the activation of protein kinase C (PKC) and required increased steady-state messenger RNA levels and de novo protein synthesis. Although VEGF-induced EC proliferation was inhibited by both p38 and p42/44 mitogen-activated protein kinase (MAPK) antagonists, DAF up-regulation in response to VEGF was only sensitive to inhibition of p38 MAPK. VEGF-stimulated EC showed a 60% reduction in C3 deposition following complement activation, and this resulted in a marked reduction in complement-mediated EC lysis. These protective effects were abolished by anti-DAF monoclonal antibody 1H4. CONCLUSION: This study confirms the importance of PKC for the regulation of DAF expression by EC and reveals VEGF to be a physiologic agonist for this pathway. The up-regulation of DAF expression by VEGF may represent an important mechanism for the protection of EC from complement-mediated injury during angiogenesis in inflammatory rheumatic diseases. PMID- 11212154 TI - The MICA region determines the first modifier locus in familial Mediterranean fever. AB - OBJECTIVE: Familial Mediterranean fever (FMF) is a genetically recessive inflammatory disease caused by mutations in the MEFV gene. Most patients of non Ashkenazi Jewish ancestry or those who are homozygous for M694V manifest a severe disease course, but some express a mild form of the disease. We therefore searched for other genes which could possibly be implicated in the disease phenotype. We tested MICA (major histocompatibility complex class I chain-related gene A) because it has been associated with a number of other inflammatory disorders. METHODS: One hundred fifty FMF probands and their family members were evaluated. The MEFV gene was screened by a combination of denaturing gradient-gel electrophoresis, restriction fragment length polymorphism, and amplification refractory mutation system. The MICA transmembrane polymorphism in exon 5 was analyzed after biotin-labeled polymerase chain reaction products were loaded onto sequencing gels and subjected to autoradiography. RESULTS: The contribution of MICA to the FMF phenotype was confirmed after adjustment for the patient's ancestry and for the MEFV genotype. MEFV was individually the most important prognostic factor for the disease. However, the impact of M694V homozygosity on the age at disease onset (OR 2.3) was aggravated if patients also inherited MICA A9 (OR 6.3). In contrast, the frequency of attacks was found to be dramatically reduced (OR 0.16) in patients with MICA-A4. CONCLUSION: We have identified the first FMF modifier locus, MICA. FMF is the first model of a Mendelian disease associated with MICA. These results clarify, at least partly, the inconsistent phenotype-MEFV correlation in FMF. PMID- 11212153 TI - Insights from a novel three-dimensional in vitro model of lyme arthritis: standardized analysis of cellular and molecular interactions between Borrelia burgdorferi and synovial explants and fibroblasts. AB - OBJECTIVE: To develop a novel 3-dimensional (3-D) in vitro model of Lyme arthritis to use in the study of the interactions between Borrelia burgdorferi (Bb) and human synovial host cells with respect to phagocytosis and potential persistence of Bb as well as the induction of proinflammatory cytokines and chemokines. METHODS: Two distinct culture systems, consisting of synovial membrane explants or interactive synovial cells embedded in 3-D fibrin matrices, were chosen. Both systems were artificially infected with Bb, and the interactions between Bb and synovial tissue/cells were studied by histology, immunohistochemistry, and electron microscopy. Functional analyses included the induction/secretion of cytokines by Bb in the model system. RESULTS: Both culture systems proved to be stable and reproducible. The host cells and spirochetes showed high levels of viability and maintained their physiologic shape for >3 weeks. Bb invaded the synovial tissue and the artifical matrix in a time dependent manner. Host cells were activated by Bb, as indicated by the induction of interleukin-1beta and tumor necrosis factor alpha. Electron microscopic analysis revealed Bb intracellularly within macrophages as well as synovial fibroblasts, suggesting that not only professional phagocytes, but also resident synovial cells are capable of phagocytosing Bb. Most interestingly, the uptake of the spirochetes appeared to cause severe damage of the synovial fibroblasts, since the majority of these cells displayed ultrastructural features of disintegration. CONCLUSION: A novel 3-D in vitro model has been established that allows the study of distinct aspects of Lyme arthritis under conditions that resemble the pathologic condition in humans. This reproducible, standardized model supplements animal studies and conventional 2-D cultures. The disintegration of synovial fibroblasts containing Bb or Bb fragments challenges the concept of an intracellular persistence of Bb and may instead reflect a mechanism that contributes to the inflammatory processes characteristic of Lyme arthritis. PMID- 11212155 TI - Clinical Images:Lupus erythematosus cells in the kidney and synovial fluid. PMID- 11212156 TI - Treatment of lupus-induced thrombocytopenia with recombinant human interleukin 11. AB - Autoimmune thrombocytopenia can be a serious manifestation of systemic lupus erythematosus (SLE) which necessitates treatment with immunosuppressive agents and platelet transfusions. Interleukin-11 (IL-11) is a unique thrombopoietic growth factor which causes proliferation of megakaryocyte progenitors as well as induces megakaryocytic maturation. To our knowledge, this agent has not been used in the treatment of autoimmune thrombocytopenia, since theoretically there is a danger of IL-11 stimulating the immune system by up-regulating the lymphoid stem cells. We describe a 36-year-old splenectomized woman with known SLE who presented with pulmonary hemorrhage, acute renal failure, change in mental status, and severe thrombocytopenia (platelet count 2,000/mm3). Her pulmonary, renal, and central nervous system complications responded to intensive therapy with intravenous (IV) pulse methylprednisone and cyclophosphamide along with hemodialysis. The thrombocytopenia remained refractory to the above treatment plus daily multiple platelet transfusions and IV immunoglobulin. Treatment with recombinant human IL-11 (25 microg/kg/day subcutaneously) was initiated and continued for 5 days. Her platelet count improved to 25,000/mm3 within 48 hours, and she experienced no adverse effects. PMID- 11212157 TI - Genetic association between interleukin-10 promoter region polymorphisms and primary Sjogren's syndrome. AB - OBJECTIVE: To determine whether the haplotypes formed on the basis of single-base exchange polymorphisms at positions -1082, -819, or -592 of the interleukin-10 (IL-10) gene predispose subjects to primary Sjogren's syndrome (SS). METHODS: The frequency of IL-10 polymorphisms was analyzed in 62 patients with primary SS and in 400 healthy subjects. These data were assessed for correlations with the concentration of IL-10 in the plasma. RESULTS: The frequency of the IL-10 GCC haplotype (G at position -1082, C at position -819, and C at position -592 of the IL-10 gene) was increased (P < 0.05, odds ratio [OR] 1.90, 95% confidence interval [95% CI] 0.955-3.62) and the frequency of the ACC haplotype decreased (P < 0.05, OR 0.443, 95% CI 0.257-0.764) in primary SS patients compared with healthy controls. Moreover, the frequency of the ATA haplotype was similar in primary SS patients and healthy controls, but the incidence of the GCC/ATA genotype was elevated in the primary SS patients (P < 0.05, OR 2.19, 95% CI 1.19 4.03). The concentration of plasma IL-10 was significantly higher in patients carrying the GCC haplotype than in non-carriers of GCC. CONCLUSION: These results suggest that the presence of the GCC haplotype or the GCC/ATA genotype and the absence of the ACC haplotype of the IL-10 gene are associated with an increased susceptibility to primary SS. This effect is probably mediated by the increased capability to produce IL-10 among carriers of the GCC haplotype. PMID- 11212158 TI - Efficacy of celecoxib, a cyclooxygenase 2-specific inhibitor, in the treatment of ankylosing spondylitis: a six-week controlled study with comparison against placebo and against a conventional nonsteroidal antiinflammatory drug. AB - OBJECTIVE: To evaluate the short-term efficacy of celecoxib, a cyclooxygenase 2 specific inhibitor, in the treatment of ankylosing spondylitis (AS). METHODS: The study was a 6-week randomized, double-blind, placebo-controlled trial with 3 treatment arms: placebo, ketoprofen 100 mg twice daily, and celecoxib 100 mg twice daily. Patients who had AS according to the modified New York criteria, without peripheral synovitis and with active disease (pain > or =40 mm on a 100 mm visual analog scale [VAS] and an increase in pain of at least 30% after nonsteroidal antiinflammatory drug withdrawal) were eligible for study. Primary outcome measures were change in pain intensity (VAS) and change in functional impairment (Bath Ankylosing Spondylitis Functional Index [BASFI]). RESULTS: Of the 246 randomized patients, 76 were allocated to receive placebo, 90 ketoprofen, and 80 celecoxib. There were no statistically significant differences between treatment groups at study entry. During the 6 weeks of the study, the decrease in pain and functional impairment was greater in the active treatment groups than in the placebo group, with a trend in favor of celecoxib when the 2 active treatments were compared. The mean changes were -13 mm, -21 mm, and -27 mm (P = 0.006) for pain and 1, -6, and -12 (P = 0.0008) for BASFI score in the placebo, ketoprofen, and celecoxib groups, respectively. During treatment, the number of patients reporting epigastric pain was 6 (8%), 13 (14%), and 10 (13%) in the placebo, ketoprofen, and celecoxib groups, respectively. CONCLUSION: The results of this study confirm the clinically relevant antiinflammatory effect of celecoxib at a 200-mg daily dosage, with significant improvement of both pain and function in patients with AS. PMID- 11212159 TI - Immunomodulatory effects of anti-tumor necrosis factor alpha therapy on synovium in spondylarthropathy: histologic findings in eight patients from an open-label pilot study. AB - OBJECTIVE: To assess the effects of treatment with anti-tumor necrosis factor alpha (anti-TNFalpha) on synovial histology in patients with spondylarthropathy (SpA) in order to confirm the effect on peripheral synovitis and to investigate the immunologic mechanisms involved in anti-TNFalpha therapy. METHODS: Patients with treatment-resistant SpA were treated with infliximab (5 mg/kg) at weeks 0, 2, and 6 in an open-label pilot study. In 8 patients, synovial biopsy tissues obtained at baseline, week 2, and week 12 were used for histologic and immunohistochemical evaluation. RESULTS: In all 8 patients (3 with ankylosing spondylitis, 1 with undifferentiated SpA, and 4 with psoriatic arthritis), there was a clear clinical improvement in the peripheral arthritis after anti-TNFalpha therapy. Histologic analysis of the synovial biopsy tissues indicated that the synovial lining layer thickness tended to decrease, with a significant reduction of CD55+ synoviocytes, at week 12. In the sublining layer, vascularity was reduced at week 12, with a decreased endothelial expression of vascular cell adhesion molecule 1 but not intercellular adhesion molecule 1, platelet endothelial cell adhesion molecule 1, and E-selectin. Although at week 2 and week 12, the number of neutrophils and CD68+ macrophages in the sublining layer was decreased, the overall degree of inflammatory infiltration remained unchanged. This could be related to the lymphocyte infiltration since at week 12, only CD4+ cells (but not CD3+, CD45RO+, and CD8+ cells) tended to decrease, while CD20+ lymphocytes and plasma cells were clearly increased. CONCLUSION: The reduction in lining layer thickness, vascularity, and infiltration with neutrophils and macrophages paralleled the beneficial effect of anti-TNFalpha therapy on peripheral synovitis in 8 patients with different subtypes of SpA. The adhesion molecule expression, T cell infiltration, and, most important, B cell infiltration seemed to contrast with previous observations in RA. Although these preliminary data need to be confirmed in a larger cohort, they suggest distinct immunomodulatory mechanisms of anti-TNFalpha in SpA. PMID- 11212160 TI - A functional polymorphic variant in the interleukin-6 gene promoter associated with low bone resorption in postmenopausal women. AB - OBJECTIVE: To examine functional interleukin-6 (IL-6) -174 G-->C allelic variants in relation to bone turnover and bone mineral density (BMD) in postmenopausal women. METHODS: Four hundred thirty-four healthy women living in the community (mean +/- SD age 71.7 +/- 5.7 years) were genotyped for the IL-6 -174 G-->C polymorphism. Serum levels of C-telopeptide of type I collagen (CTx), a marker of bone resorption, and osteocalcin (OC), a marker of bone formation, were determined. BMD at the hip and forearm was measured by dual-energy x-ray absorptiometry. RESULTS: CTx levels differed significantly (P = 0.006) among IL-6 genotypes (mean +/- SEM 0.275 +/- 0.02 ng/ml, 0.325 +/- 0.01 ng/ml, and 0.356 +/- 0.02 ng/ml in women with the CC genotype [n = 68], the GC genotype [n = 204], and the GG genotype [n = 162], respectively). Compared with the GG group, age adjusted odds ratios for high bone resorption were 0.65 (95% confidence interval [95% CI] 0.41-1.0, P = 0.06) and 0.37 (95% CI 0.18-0.73, P = 0.0047) in GC and CC subjects, respectively. In contrast, OC levels did not differ by genotype. BMD at the hip and forearm was 1.5-5% higher in CC subjects compared with GG subjects (P not significant). When the cohort was divided according to the median age (70.5 years), BMD was significantly decreased in older compared with younger postmenopausal women with the GG and GC genotypes (-9.6% on average; P < 0.01), but not in those with the CC genotype (-5.1% on average; P not significant). CONCLUSION: Compared with the GC and GG IL-6 -174 G-->C genotypes, the CC genotype is associated with lower bone resorption and lesser decrease in bone mass in older postmenopausal women. These results suggest that IL-6 -174 G-->C alleles may be significant determinants of the risk for osteoporosis in elderly subjects. PMID- 11212161 TI - Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids: a randomized, double-blind, placebo controlled extension trial. AB - OBJECTIVE: To evaluate the continued efficacy and safety of alendronate (ALN) for up to 2 years in patients receiving glucocorticoids. METHODS: This is a 12-month extension of a previously completed 1-year trial of daily ALN, performed to evaluate the effects of ALN over a total of 2 years in 66 men and 142 women continuing to receive at least 7.5 mg of prednisone or equivalent daily. All patients received supplemental calcium and vitamin D. The primary end point was the mean percentage change in lumbar spine bone mineral density (BMD) from baseline to 24 months. Other outcomes included changes in hip and total body BMD, biochemical markers of bone turnover, radiographic joint damage of the hands, and vertebral fracture incidence. RESULTS: The mean (+/-SEM) lumbar spine BMD increased by 2.8 +/- 0.6%, 3.9 +/- 0.7%, and 3.7 +/- 0.6%, respectively, in the groups that received 5 mg, 10 mg, and 2.5/10 mg of ALN daily (P < or = 0.001) and decreased by -0.8 +/- 0.6% in the placebo group (P not significant) over 24 months. In patients receiving any dose of ALN, BMD was increased at the trochanter (P < or = 0.05) and maintained at the femoral neck. Total body BMD was increased in patients receiving 5 or 10 mg ALN (P < or = 0.01). These 2 dose levels of ALN were more effective than placebo at all sites (P < or = 0.05). Bone turnover markers (N-telopeptides of type I collagen and bone-specific alkaline phosphatase) decreased 60% and 25%, respectively, during treatment with ALN (P < or = 0.05). There were fewer patients with new vertebral fractures in the ALN group versus the placebo group (0.7% versus 6.8%; P = 0.026). The safety profile was similar between treatment groups. CONCLUSION: Alendronate is an effective, well-tolerated therapy for the prevention and treatment of glucocorticoid-induced osteoporosis, with sustained treatment advantages for up to 2 years. PMID- 11212162 TI - Rheumatoid arthritis synovial macrophages express the Fas-associated death domain like interleukin-1beta-converting enzyme-inhibitory protein and are refractory to Fas-mediated apoptosis. AB - OBJECTIVE: The chronic inflammation and progressive joint destruction observed in rheumatoid arthritis (RA) are mediated in part by macrophages. A paucity of apoptosis has been observed in RA synovial tissues, yet the mechanism remains unknown. The present study sought to characterize the expression of Fas, Fas ligand (FasL), and Fas-associated death domain-like interleukin-1beta-converting enzyme-inhibitory protein (FLIP), and to quantify the apoptosis induced by agonistic anti-Fas antibody, using mononuclear cells (MNC) isolated from the peripheral blood (PB) and synovial fluid (SF) of RA patients. METHODS: The expression of Fas, FasL, and FLIP and apoptosis induced by agonistic anti-Fas antibody in MNC from the PB and SF of RA patients were determined by flow cytometry. Immunohistochemistry employing a monospecific anti-FLIP antibody was performed on RA and osteoarthritis (OA) synovial tissue. RESULTS: CD14-positive monocyte/macrophages from normal and RA PB and from RA SF expressed equivalent levels of Fas and FasL. Furthermore, unlike the CD14-positive PB monocytes, RA SF monocyte/macrophages were resistant to the addition of agonistic anti-Fas antibody. In contrast, both CD14-positive PB and SF monocyte/macrophages were sensitive to apoptosis mediated by a phosphatidylinositol 3-kinase inhibitor. Intracellular staining of the caspase 8 inhibitor, FLIP, in CD14-positive SF monocyte/macrophages revealed a significant up-regulation of FLIP compared with normal and RA PB monocytes. Immunohistochemical analysis of synovial tissue from RA and OA patients revealed increased FLIP expression in the RA synovial lining compared with the OA synovial lining. Furthermore, FLIP expression was observed in the CD68positive population in the RA synovial lining. Forced reduction of FLIP by a chemical inhibitor resulted in RA SF macrophage apoptosis that was enhanced by agonistic anti-Fas antibody, indicating that FLIP is necessary for SF macrophage survival. CONCLUSION: These data suggest that up-regulation of FLIP in RA macrophages may account for their persistence in the disease. Thus, the targeted suppression of FLIP may be a potential therapeutic strategy for the amelioration of RA. PMID- 11212163 TI - Arthritis prevalence and activity limitations in older adults. AB - OBJECTIVE: To evaluate the prevalence of arthritis and activity limitations among older Americans by assessing their demographic, ethnic, and economic characteristics. METHODS: Data from the Asset and Health Dynamic Survey Among the Oldest Old (AHEAD), a national probability sample of community-dwelling adults born before 1924, were analyzed cross-sectionally. Arthritis that resulted in a physician's visit or a joint replacement not associated with a hip fracture was ascertained by self-report. RESULTS: The prevalence of arthritis in older adults ranged from 25% in non-Hispanic whites to 40% in non-Hispanic blacks to 44% in Hispanics. A higher prevalence of arthritis was associated with less education as well as lower income and less wealth. The prevalence of limitations in activities of daily living (ADL) among non-Hispanic white, non-Hispanic black, and Hispanic adults who reported arthritis only was 29%, 30%, and 37%, respectively, and increased to 48%, 57%, and 56%, respectively, among those reporting arthritis plus other chronic conditions, after adjustment for age and sex. CONCLUSION: Non Hispanic black and Hispanic older adults reported having arthritis at a substantially higher frequency than did non-Hispanic whites. In addition, Hispanics reported higher rates of ADL limitations than did non-Hispanic whites with comparable disease burden. Further study is needed to confirm and elucidate the reasons for these racial and economic disparities in older populations. PMID- 11212164 TI - Alpha sleep characteristics in fibromyalgia. AB - OBJECTIVE: To characterize the patterns of alpha electroencephalographic sleep and their associations with pain and sleep in patients with fibromyalgia. METHODS: Pain and sleep symptoms of 40 female patients with fibromyalgia and 43 healthy control subjects were studied before and after overnight polysomnography. Blinded analyses of alpha activity in non-rapid eye movement (non-REM) sleep were performed using time domain, frequency domain, and visual analysis techniques. RESULTS: Three distinct patterns of alpha sleep activity were detected in fibromyalgia: phasic alpha (simultaneous with delta activity) in 50% of patients, tonic alpha (continuous throughout non-REM sleep) in 20% of patients, and low alpha activity in the remaining 30% of patients. Low alpha activity was exhibited by 83.7% of control subjects (P < 0.01). All fibromyalgia patients who displayed phasic alpha sleep, activity reported worsening of pain after sleep, compared with 58.3% of patients with low alpha activity (P < 0.01) and 25.0% of patients with tonic alpha activity (P < 0.01). Postsleep increase in the number of tender points occurred in 90.0% of patients with phasic alpha activity, 41.7% of patients with low alpha activity, and 25.0% of patients with tonic alpha activity (P < 0.01). Self ratings of poor sleep were reported by all patients with phasic alpha activity, 58.3% of patients with low alpha activity (P < 0.01), and 12.5% of patients with tonic alpha activity (P < 0.01). Patients with phasic alpha activity reported longer duration of pain than patients in other subgroups (P < 0.01). Additionally, patients with phasic alpha sleep activity exhibited less total sleep time than patients in other subgroups (P < 0.05), as well as lower sleep efficiency (P < 0.05) and less slow wave sleep (P < 0.05) than patients with a tonic alpha sleep pattern. CONCLUSION: Alpha intrusion during sleep can be of different patterns. Phasic alpha sleep activity was the pattern that correlated better with clinical manifestations of fibromyalgia. PMID- 11212165 TI - Efficacy and safety of desensitization to allopurinol following cutaneous reactions. AB - OBJECTIVE: To evaluate the long-term efficacy and safety of slow oral desensitization in the management of patients with hyperuricemia and allopurinol induced maculopapular eruptions. METHODS: A retrospective evaluation of an oral desensitization regimen using gradual dosage-escalation of allopurinol in 32 patients (30 with gout and 2 with chronic lymphocytic leukemia) whose therapy was interrupted because of a pruritic cutaneous reaction to the drug. RESULTS: Twenty one men and 11 women with a mean age of 63 years (range 17-83 years), a mean serum urate level of 618 micromoles/liter (range 495-750) (or, mean 10.4 mg/dl [range 8.3-12.6]), and a mean serum creatinine level of 249 micromoles/liter (range 75-753) (or, mean 2.8 mg/dl [range 0.8-8.5]) were studied. Desensitization failed in 4 patients because of unmanageable recurrent rash. Twenty-eight patients completed the desensitization procedure to a target allopurinol dosage of 50-100 mg/day, 21 without deviation from the protocol for a mean of 30.5 days (range 21-56 days) and 7 requiring dosage adjustments because of a recurrent rash over 53.8 days (range 40-189 days). Seven of these 28 patients developed late cutaneous reactions 1-20 months postdesensitization, 4 responding to dosage modification and 3 discontinuing the drug. Twenty-five of the 32 patients (78%) continued to take allopurinol; their mean duration of followup was 32.6 months (range 3-92 months) and the mean postdesensitization serum urate level was 318 micromoles/liter (range 187-452) (or, mean 5.3 mg/dl [range 3.0-7.5]). CONCLUSION: The study confirms the long-term efficacy and safety of slow oral desensitization to allopurinol in patients with maculopapular eruptions, particularly in those with gout, who cannot be treated with uricosurics or other urate-lowering drugs. Although pruritic skin eruptions may recur both during and after desensitization, most of these cutaneous reactions can be managed by temporary withdrawal of allopurinol and dosage adjustment. PMID- 11212166 TI - Evidence for linkage of the HLA-B locus in Behcet's disease, obtained using the transmission disequilibrium test. PMID- 11212167 TI - Beneficial effect of etanercept on rheumatoid lymphedema. PMID- 11212168 TI - Clinical images: Cervical spinal cord compression. PMID- 11212169 TI - Increase in the heart rate-corrected QT interval in children of anti-Ro-positive mothers, with a further increase in those with siblings with congenital heart block: comment on the article by Cimaz et al. PMID- 11212170 TI - Shrinking lung syndrome in patients without systemic lupus erythematosus: comment on the concise communication by Tavoni et al. PMID- 11212171 TI - Similar effects of pulse corticosteroid and tumor necrosis factor alpha blockade in rheumatoid arthritis: comment on the article by Taylor et al. PMID- 11212172 TI - Synergistic activity of interleukin-4 and interleukin-10 in suppression of inflammation and joint destruction in rheumatoid arthritis. PMID- 11212173 TI - Regulation of angiogenesis by the C-X-C chemokines interleukin-8 and epithelial neutrophil activating peptide 78 in the rheumatoid joint. AB - OBJECTIVE: Angiogenesis, the growth of new blood vessels, is vital to the ingress of inflammatory leukocytes in rheumatoid arthritis (RA) synovial tissue and to the growth and proliferation of RA pannus. The factors that mediate the growth of new blood vessels have not been completely defined. This study examined the ability of Glu-Leu-Arg (ELR)-containing chemokines to induce angiogenesis in the RA joint. METHODS: To reflect angiogenic activity in vivo, we selected a model using whole human synovial tissue rather than isolated cells. Tissues were examined by immunohistochemistry and enzyme-linked immunosorbent assay, and tissue homogenates were immunoneutralized and assayed for their ability to induce endothelial cell chemotaxis and rat corneal neovascularization. RESULTS: Cells expressing interleukin-8 (IL-8) and epithelial neutrophil activating peptide 78 (ENA-78) were located in proximity to factor VIII-related antigen-immunopositive endothelial cells. RA homogenates produced more IL-8 and ENA-78 compared with normal synovial tissue homogenates. Moreover, homogenates from RA synovial tissue produced significantly more chemotactic activity for endothelial cells in vitro and angiogenic activity in the rat cornea in vivo than did normal synovial tissue homogenates. The effects of IL-8 and ENA-78 accounted for a significant proportion of the chemotactic activity of endothelial cells and angiogenic activity found in RA synovial tissue homogenates. CONCLUSION: These results indicate that the ELR-containing chemokines IL-8 and ENA-78 are important contributors to the angiogenic activity found in the inflamed RA joint. It is possible that efforts aimed at down-regulating these chemokines offer a novel targeted therapy for the treatment of RA. PMID- 11212174 TI - Secretion of anti-citrulline-containing peptide antibody by B lymphocytes in rheumatoid arthritis. AB - OBJECTIVE: To understand the regulation of anti-citrulline-containing peptide antibody (anti-CCP) production in rheumatoid arthritis (RA), production of anti CCP by B cells derived from peripheral blood (PB), bone marrow (BM), and synovial fluid (SF) was examined. METHODS: Purified PB and SF B cells were isolated by negative selection and then cultured in the absence or presence of L-CD40 ligand cells and interleukin-10 or anti-CD3-activated T cells. Total IgM and IgM-anti CCP were detected after 14 days of culture by enzyme-linked immunosorbent assay. Enzyme-linked immunospot assays were performed to analyze the frequency of cells that spontaneously produced IgM-anti-CCP in BM and SF B cells. RESULTS: IgM-anti CCP autoantibodies were induced in PB B cells from healthy controls and RA patients following coculture with activated T cells or application of the CD40 activation system, whereas no production could be detected when PB B cells were cultured in the absence of a stimulus. SF and BM B cells from anti-CCP seropositive RA patients, but not anti-CCP-seronegative patients, actively produced IgM-anti-CCP without stimulation. The frequency of spontaneous production of IgM-anti-CCP among the IgM-secreting cells ranged from 2.2% to 25%. CONCLUSION: These results indicate the presence of B cell precursors for anti-CCP autoantibodies that are able to produce antibodies upon stimulation in the PB B cell repertoire of healthy controls and patients with RA. In contrast, B cells that actively secreted anti-CCP were specifically present in the BM and SF compartment of anti-CCP-seropositive RA patients. The local presence of anti-CCP secreting cells in the inflamed joints provides evidence for an antigen-driven maturation of CCP-specific B cells at the site of inflammation in RA. PMID- 11212175 TI - The influence of synovial fluid on adenovirus-mediated gene transfer to the synovial tissue. AB - OBJECTIVE: To determine the effect of synovial fluid (SF) from rheumatoid arthritis (RA) patients on adenovirus type 5 (Ad5)-mediated gene transfer to synoviocytes, and to explore new strategies for vector development based on the neutralization data obtained. METHODS: SF was derived from 63 randomly selected R4 patients. Ten samples were used to study the effect of SF on Ad5-mediated gene transfer in synoviocytes. IgG and <100-kd fractions were purified from these 10 SF, and their effect on gene transfer was determined. Neutralizing activity against wild-type Ad5 (wt-Ad5), wt-Ad26, wt-Ad34, wt-Ad35, and wt-Ad48 was tested in the SF from the remaining 53 patients. RESULTS: Seven of 10 SF samples inhibited Ad5-mediated gene transfer. Purified antibodies exhibited inhibition patterns similar to those seen with unfractionated SF. In 5 of 10 SF samples, low molecular weight fractions inhibited gene transfer at low dilutions. Neutralization of wt-Ad35 by SF from RA patients was less frequent than neutralization of other wt-Ad tested (4% versus 42-72%; n = 53). CONCLUSION: SF from 70% of the RA patients contained neutralizing antibodies that hamper Ad5 mediated gene transfer to synoviocytes. The activity of neutralizing antibodies may be circumvented in the majority of RA patients when vectors based on an Ad35 backbone are used. PMID- 11212176 TI - Responsiveness of the self-assessed rheumatoid arthritis disease activity index to a flare of disease activity. AB - OBJECTIVE: To assess the responsiveness of the Rheumatoid Arthritis Disease Activity Index (RADAI) to increases in disease activity, using the occurrence of a flare of disease activity as an external standard. METHODS: A post hoc analysis was performed on data from a randomized, double-blind, controlled trial of methotrexate versus type II collagen in 92 patients with rheumatoid arthritis (RA). Responsiveness was analyzed by 1) correlating change in the RADAI score with change in the Disease Activity Score (DAS28), 2) determining the RADAI's ability to detect a disease flare by plotting a receiver operating characteristic (ROC) curve, and 3) using a responsiveness statistic, the standardized effect size (SES). The contribution of the single RADAI items to the change in total RADAI score was analyzed by the item score change in absolute value, the item responsiveness by the standardized response mean, and the correlation of item score change with total RADAI score change by Cronbach's alpha. RESULTS: Changes in the RADAI score correlated strongly with changes in the DAS28 (R2 = 0.70, P < 0.0001). The area under the ROC curve for the RADAI was 0.88 (95% confidence interval 0.78-0.95), which was similar to that for the DAS28. The SES for the RADAI was 1.56, which was also similar to that for the DAS28. The RADAI items of past global disease activity and morning stiffness contributed least to the total score change. CONCLUSION: This study provides evidence that the RADAI is sensitive to relevant increases in disease activity in RA patients. The RADAI may complement clinical measures in clinical studies, or may be used as a proxy for disease activity in epidemiologic studies. PMID- 11212177 TI - Association between rheumatoid arthritis and polymorphism of tumor necrosis factor receptor II, but not tumor necrosis factor receptor I, in Caucasians. AB - OBJECTIVE: Tumor necrosis factor (TNF) is a powerful mediator of inflammation in rheumatoid arthritis (RA). In vivo, its acute effects are limited by binding to soluble receptors (TNFR), suggesting that TNFR genes could be important candidate risk factors. The present study was undertaken to investigate association of polymorphisms of TNFRI and TNFRII with RA in subjects in the UK. METHODS: Unrelated Caucasian RA patients (n = 291) and healthy Caucasian controls (n = 143) were genotyped for A/G polymorphism in exon 1 of TNFRI. From this sample, 240 of the patients and 137 controls were also typed for a single-nucleotide polymorphism (SNP) in exon 6 of the TNFRII gene. In followup studies, DNA samples from UK Caucasian RA patients with a positive family history (n = 149) and UK Caucasian patients with sporadic RA (n = 208) were also typed for the exon 6 TNFRII polymorphism. RESULTS: TNFRI polymorphism was not associated with RA (odds ratio [OR] for GG genotype 0.93, 95% confidence interval [95% CI] 0.54-1.60). For TNFRII, in the initial study group, patients with RA were significantly more likely to be positive for both the G allele and GG genotype than were controls (OR for GG genotype 2.55, 95% CI 1.11-5.86). The association appeared to be confined to those with a family history of RA. This finding was replicated in an independent cohort of patients with familial RA. CONCLUSION: The results of this study provide evidence of association between an SNP in the TNFRII gene and RA, the strongest association being observed in patients with a family history. No evidence of association between RA and TNFRI was demonstrated. PMID- 11212178 TI - The clinical significance of amyloid fat deposits in rheumatoid arthritis: a systematic long-term followup study using abdominal fat aspiration. AB - OBJECTIVE: To analyze the prevalence of subclinical amyloid fat deposits in patients with rheumatoid arthritis (RA) and to evaluate its clinical significance. METHODS: A cohort of 313 adult RA patients were included in this prospective observational study. Systematic abdominal subcutaneous fat aspiration (ASFA) was performed on all patients at study entry. The prevalence of visceral amyloidosis at study entry and at the end of followup was analyzed for patients with a positive ASFA test result. Followup ranged from 1 to 14 years (mean +/- SD 6.7 +/- 4.1 years). Patients with clinical and subclinical amyloidosis were compared with regard to clinical characteristics and the degree of amyloid deposits in abdominal fat. RESULTS: The first ASFA test found amyloid in the abdominal fat of 51 patients (16.3%), and subsequent ASFA tests found amyloid in the abdominal fat of 10 additional patients. At the time of the ASFA test, amyloidosis was subclinical in 45 of these 61 patients, 41 of whom were followed up. During followup, 11 of these 41 patients developed renal involvement, 5 due to amyloid nephropathy. Thus, amyloidosis remained subclinical in at least 30 of 41 patients (73%) throughout followup. Marked amyloid fat deposits were found more frequently in patients with clinical amyloidosis than in those whose amyloidosis remained subclinical at the end of followup (57% versus 22%; P = 0.04). CONCLUSION: Amyloid fat deposits are not uncommon in adult RA. In the majority of patients, the deposits do not indicate clinically evident organic dysfunction, even after several years of followup. Patients with more extensive fat deposits may have a higher risk of developing clinical amyloidosis. PMID- 11212179 TI - Hepatocyte growth factor induction of collagenase 3 production in human osteoarthritic cartilage: involvement of the stress-activated protein kinase/c Jun N-terminal kinase pathway and a sensitive p38 mitogen-activated protein kinase inhibitor cascade. AB - OBJECTIVE: Osteoarthritis (OA) involves both a decreased reparative process and an increased degradative phenomenon. Several cytokines and growth factors are known to facilitate the repair of articular cartilage defects. The hepatocyte growth factor (HGF) present in OA cartilage is suggested to be involved in the cartilage repair process as well as in matrix remodeling and chondrocyte migration, leading to partial reconstruction of articular cartilage. Since cell migration is often correlated with metalloprotease activity, the effect of HGF on collagenase 3 production was studied because of its possible implication in OA cartilage remodeling. METHODS: We examined HGF-stimulated collagenase 3 production in human OA chondrocytes by Western and Northern blotting. Furthermore, we explored the intracellular signaling pathways through which HGF induced collagenase 3 production. RESULTS: This study showed that HGF stimulated collagenase 3 production in human OA chondrocytes at the transcriptional level, and this induction was mediated by activation of the stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK) pathway, but not the p38 mitogen activated protein kinase (MAPK). The p44/42 MAPKs were also phosphorylated and the use of their specific inhibitor (PD 98059) did not affect HGF-induced collagenase 3 production in OA chondrocytes. Induced collagenase 3 production via the SAPK/JNK pathway was mediated, at least in part, by the TRE site in the promoter, and in the activator protein 1 complex, c-Jun, JunD, and Fra-1 were activated. Surprisingly, further experiments revealed that the specific p38 MAPK inhibitor SB 202190 also inhibited collagenase 3 production early in the HGF induced process. The 50% inhibitory concentration was as low as 50 nM, which is unlikely to be related to p38 MAPK inhibition (which is usually in the microM range), suggesting the involvement of another kinase sensitive to SB 202190. CONCLUSION: This is the first study to show that HGF has the ability to induce both the expression and synthesis of collagenase 3 in OA chondrocytes. The effect is mediated by kinase cascades involving SAPK/JNK and another, unidentified kinase. This study provides novel information implicating a role for HGF in the pathophysiology of OA through its effect on the production of collagenase 3, which is an enzyme that is possibly involved in OA cartilage remodeling. PMID- 11212180 TI - Human periosteum-derived cells maintain phenotypic stability and chondrogenic potential throughout expansion regardless of donor age. AB - OBJECTIVE: To assess the in vitro chondrogenic potential of adult human periosteum-derived cells (PDCs) with regard to the number of cell passages and the age of the donor. METHODS: Cells were enzymatically released from the periosteum of the proximal tibia obtained from adult human donors and expanded in monolayer. PDCs were harvested at multiple passages for total RNA extraction and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) gene expression analysis. For the chondrogenesis assay, cells were plated in micromass and treated with transforming growth factor beta1 (TGFbeta1) in a chemically defined medium. At different time points, micromasses were either harvested for RT-PCR analysis for cartilage and bone markers or fixed, paraffin-embedded, and stained for cartilage matrix, and immunostained for type II collagen. RESULTS: At the first 2 passages, human PDCs from young donors formed chondrogenic nodules. This spontaneous chondrogenic activity was lost upon passaging, and it was not observed in donors older than 30 years. Using a panel of marker genes, PDCs were shown to be phenotypically stable during cell expansion. Regardless of donor age or cell passage, chondrogenesis could be induced consistently by combining micromass culture and TGFbeta1 treatment. Histochemical and immunohistochemical analyses demonstrated the hyaline-like cartilage phenotype of the tissue generated in vitro. Other TGFbeta superfamily members, such as growth differentiation factor 5/cartilage-derived morphogenetic protein 1, and bone morphogenetic proteins 2, 4, and 7, were poorly chondrogenic under the same culture conditions. CONCLUSION: Adult human PDCs have the potential to differentiate toward the chondrocytic lineage in vitro, retaining this property even after extensive subculture. Human PDCs are easily accessible, expandable, and maintain their chondrogenic potential, and are therefore promising progenitor cells for use in the repair of joint surface defects. PMID- 11212182 TI - Psychoanalysis, development, and the life cycle. PMID- 11212183 TI - The organized categories of infant, child, and adult attachment: flexible vs. inflexible attention under attachment-related stress. AB - From an evolutionary perspective, a central mechanism promoting infant survival is the maintenance of proximity to attachment figures. Consequently attachment figure(s) represent the infant's primary solution to experiences of fear. Aspects of the development of the field of attachment are outlined within this context, beginning with Bowlby's ethological/evolutionary theory, and proceeding to Ainsworth's early descriptions of infant-mother interaction in Uganda and Baltimore. Using a laboratory procedure called the strange situation, Ainsworth identified three organized patterns of infant response to separation from and reunion with the parent. Narratives derived from videotaped strange situation behavior of infants in each category (secure, avoidant, and resistant/ambivalent) are provided, together with a discussion of the prototypical sequelae of each category (e.g., school behavior, and separation-related narratives and drawings at age six). The Adult Attachment Interview (AAI) and the move to the level of representation are also described. AAI transcripts are presently analyzed according to the speaker's capacity to adhere to Grice's maxims of rational cooperative discourse, and three organized AAI categories, or states of mind with respect to attachment, have been identified (secure-autonomous, dismissing, and preoccupied). When the interview is administered to parents who have been seen with their infants in the strange situation, each AAI category has repeatedly been found to predict that infant's strange situation response to that parent. Illustrations of the discourse characteristic of each category are provided, and it is noted that individuals with apparently unfavorable life histories are found to have secure offspring, providing that their history is recounted coherently. Like infant strange situation behavior, differences in adult security as identified through discourse patterning are interpreted in terms of attentional flexibility or inflexibility under attachment-related stress. PMID- 11212181 TI - Nitric oxide regulates mitochondrial respiration and functions of articular chondrocytes. AB - OBJECTIVE: Biologic effects of nitric oxide (NO) have been shown to increase under hypoxic conditions. Because the oxygen tension in joint cavities of patients with arthritis is fairly low, biologic effects of NO would be expected to be significantly large in these compartments. This study was undertaken to investigate the effects of NO on the energy metabolism and functions of articular chondrocytes under different oxygen tension conditions. METHODS: Articular chondrocytes from rabbits were cultured under various oxygen concentrations in the presence or absence of NO and NOC18, an NO donor. Cellular respiration was measured using a Clark-type oxygen electrode. Levels of ATP in the cells were determined according to the luciferin-luciferase method. Cellular synthesis of proteoglycans was determined by measuring the incorporation of radioactivity (derived from 35S-labeled SO4) into glycosaminoglycans. Expression of stress related proteins was evaluated by Western blotting analysis using specific antibodies. RESULTS: Respiration and ATP synthesis of cultured chondrocytes were inhibited by NO, particularly under low oxygen concentrations. The presence of either NO or specific inhibitors of mitochondrial electron transport suppressed the synthesis of proteoglycans without affecting cell viability. When exposed to NO, cellular levels of heat-shock protein 70 (hsp70) and heme oxygenase 1 (HO-1) increased markedly. The presence of inhibitors of mitochondrial electron transport also increased cellular levels of hsp70 and HO-1. CONCLUSION: These results suggest that NO generated in the joint might inhibit energy metabolism and the synthesis of proteoglycans of chondrocytes, thereby modulating pathophysiologic processes occurring in patients with arthritis. PMID- 11212184 TI - Disorganized infant, child, and adult attachment: collapse in behavioral and attentional strategies. AB - This presentation focuses on the disorganized/disoriented (Group D) categories of infant, child, and adult attachment. The infant D category is assigned on the basis of interruptions and anomalies in organization and orientation observed during Ainsworth's strange situation procedure. In neurologically normal low-risk samples, D attachment is not substantially related to descriptions of infant temperament, and usually appears with respect to only one parent. At six, former D infants are often found to be role-inverting (D-Controlling) towards the parent, while drawings and separation-related narratives (D-Fearful) suggest continuing states of fear and disorganization. In adults, marked lapses in reasoning and discourse surrounding the discussion of loss or abuse during the Adult Attachment Interview (AAI) causes a transcript to be assigned to Unresolved/disorganized (U/d) adult attachment status, which predicts infant D attachment. Bowlby's theory is extended, with the proposal that certain forms of frightening parental behavior will arouse contradictory biologically channeled propensities to approach and to take flight from the parent. Maltreated infants are therefore highly likely to be disorganized. Also identified are subtler forms of frightening parental behavior (including dissociative behavior and anomalous forms of frightened behavior) that appear to lead to infant disorganization. This suggests that infant D attachment may at times represent a second-generation effect of the parent's own continuing unresolved responses to trauma. Infant D attachment predicts disruptive/aggressive and dissociative disorders in childhood and adolescence, while U/d adult attachment appears frequently in psychiatric and criminal populations. Clinical implications are discussed. PMID- 11212185 TI - Attachment and borderline personality disorder. AB - The author outlines his concept of reflective function or mentalization, which is defined as the capacity to think about mental states in oneself and in others. He presents evidence to suggest that the capacity for reflective awareness in a child's caregiver increases the likelihood of the child's secure attachment, which in turn facilitates the development of mentalization in the child. He proposes that a secure attachment relationship offers the child a chance to explore the mind of the caregiver, and in this way to learn about minds; he formulates this model of the birth of the psychological self as a variation on the Cartesian cogito: "My caregiver thinks of me as thinking and therefore I exist as a thinker." This model is then applied to provide insight into some personality-disordered individuals who were victims of childhood abuse. The author proposes (1) that individuals who experience early trauma may defensively inhibit their capacity to mentalize to avoid having to think about their caregiver's wish to harm them; and (2) that some characteristics of severe borderline personality disorder may be rooted in developmental pathology associated with this inhibition. He offers evidence for and some qualifications of this model, and argues that the therapeutic effect of psychoanalysis depends on its capacity to activate patients' ability to evolve an awareness of mental states and thus find meaning in their own and other people's behavior. PMID- 11212186 TI - The development and organization of attachment: implications for psychoanalysis. AB - As a result of John Bowlby's breach with the British Psychoanalytic Society nearly forty years ago, his work, specifically the development of attachment theory, was until recently largely expunged from the psychoanalytic record. However, thanks to developments in both psychoanalytic and attachment theories, a rapprochement has been forged, and a number of scholars are now seeking to integrate these two complementary perspectives. In this paper, the fundamental premises of attachment theory are discussed in light of their relation to psychoanalytic theory. In addition, their application to the clinical situation in both adult and child treatment is discussed. PMID- 11212187 TI - Clinical implications of current attachment theory. Panel report. PMID- 11212188 TI - Reapproaching Mahler: new perspectives on normal autism, symbiosis, splitting and libidinal object constancy from cognitive developmental theory. AB - Margaret Mahler's seminal work on the psychological birth of the infant has generated more critical discussion than most other psychoanalytic theories of early development. But while the empirically, theoretically, and methodologically based criticisms of Mahler's theory are generally justified, her critics fail at times to consider some of the intriguing and creative insights that her theoretical formulations tried to capture. This paper attempts to reformulate these insights using the new conceptual tools that current cognitive developmental theory provides. Mahler's stage of normal autism is reconsidered in the light of contingency detection theory as an initial phase of primary preoccupation with self-generated perfectly response-contingent stimulation. Her concept of normal symbiosis is recast with the help of attachment theory's views on homeostatic regulation and the social biofeedback model of affect-reflective mirroring interactions with parents. Finally, her ideas about the development of splitting and libidinal object constancy are reconsidered according to recent theories of early representational development and mentalization. PMID- 11212189 TI - On the vicissitudes of early primary surrogate mothering II: loss of the surrogate mother and arrest of mourning. AB - Among the catastrophic events experienced by infants and young children, one of the most frequent is the loss of an early primary surrogate mother (EPSM). Usually permanent, the loss is often followed by the advent of a new, "replacement" caregiver. One aspect of the emotional environment is unique to this kind of caregiving situation: that parents are often unable to validate the true nature of their child's relationship with the EPSM or, ultimately, the trauma experienced by the child when the EPSM leaves. The marked discrepancy between the parent's and the infant or child's experience of the surrogate mothering leads to an arrest of the child's mourning process, with the potential for serious developmental consequences. Issues related to EPSM loss and its aftermath are examined in the light of two examples. Further exploration of the environment of this kind of caregiving directs attention to the critical need to nurture and protect the attachments of both the infant or child and the parent to the ESPM. PMID- 11212190 TI - A psychoanalytic perspective on attention-deficit/hyperactivity disorder. AB - Psychoanalysts have tended to view the diagnosis of AD/HD either with skepticism or as a contraindication to analytic treatment. The author reviews the history of this puzzling diagnostic entity, which is estimated to account for up to fifty percent of child referrals, and suggests that a psychoanalytic perspective on the underlying disturbance in ego functioning helps to clarify the nature of the symptom picture. Whatever the etiology, which may be compound, she suggests that psychoanalytic treatment, most often in conjunction with psychopharmacological therapy, can address the core disturbance in ego integration that creates the familiar triad of inattention, impulsivity, and hyperactivity. PMID- 11212191 TI - The Adam and Eve story as exemplar of an early-life variant of the oedipus complex. AB - The Adam and Eve story is construed as having an organizing function that facilitates the analytic understanding of certain patients. In this interpretation, the story epitomizes a psychodynamic in which progressive growth, with separation and individuation, of the young is experienced as perilous--not only to them, but also correspondingly to their procreators. In the myth, the increasing psychic and physical maturation of Adam and Eve produced a crisis. Not only was divine authority flouted, but also apprehensions were aroused that God might be humbled or diminished. This threatened him, evoking his wrath and leading to the punishment by abandonment of his youthful wards. It is suggested that the story depicts an emotional complex of widespread application and is an archaic version of the oedipus complex, continuous with the oedipus complex proper, but from an earlier stage of development. This archaic complex is delineated with clinical vignettes, and a clinical explication of its various components is provided. Clinical management is considered, particularly with reference to the challenge that a closed-system perspective (Fairbairn 1958) presents to a patient's development. PMID- 11212192 TI - Encopresis and anal masturbation. AB - Current pediatric and psychiatric studies on encopresis and its treatment are heavily influenced by mechanical, physiological, and behavioral considerations. Although psychodynamic treatment has generally been considered to be of little benefit, and its findings suspect, the authors suggest that a psychodynamic approach adds substantially to the understanding of some cases of encopresis; that the anal sensations and anal erotic feelings reported by a number of encopretic children are intense, and that the encopretic symptom, soiling, in these children is the result of a conscious form of anal masturbation in which the fecal mass is used for stimulation; and that any study of encopresis is incomplete that does not include what encopretic children, engaged in a sound therapeutic relationship, know and say about their soiling. The authors further suggest that physical treatments of those children whose encopresis is psychologically driven may be contraindicated. The presence of a large stool does not in itself substantiate a physical illness. Further research is needed to elucidate the prevalence of anal masturbation in encopretic children. PMID- 11212193 TI - Primary femininity: clinical advances and theoretical ambiguities. AB - This paper examines the use of the term "primary femininity" in current psychoanalytic thinking. The concept of primary femininity arose in reaction to early theories about female sexuality and development; based on a model of male development, these presented problems when applied to females. The author attempts to demonstrate the clinical advances that have resulted from the idea of primary femininity. At the same time she argues that the idea has been used to carry widely differing meanings, and has reflected many writers' differing frames of reference, which range from gender identity through biological traits, object relations, genital anxieties, and bisexuality. Like the terms it originally was intended to replace or augment, it has come to be used reductionistically or loosely. The author warns against its misuse and argues that primary femininity is not a unitary concept, but rather encompasses a related group of ideas about the female body and mind. PMID- 11212194 TI - Body ego and the preoedipal roots of feminine gender identity. AB - Traditionally, visual cues (that is, seeing the difference between one's own genitals and those of the opposite sex) and the fantasies that they prompt were thought to be the central determinants in the organization of gender identity. More recently attention has been focused on mother-infant interaction patterns, on the construction of the body itself, on its kinesthetic sensations, and on the fantasies that these evoke. These matters are now thought to be equal in importance to the traditional considerations. The resulting concept of a core gender identity has suggested the possibility of various forms of preoedipal genital anxiety. This paper discusses how two experiences common to childhood as well as adulthood--the tumescence of erectile tissue and the involuntary vaginal secretions of sexual arousal--may contribute to the organization of feminine gender identity. Case material, including a close examination of an analytic hour, is presented to show how this process may manifest itself in adult neurotic conflict. PMID- 11212195 TI - The feminization of the female oedipal complex, Part I: a reconsideration of the significance of separation issues. AB - Freud's insights about the oedipus complex have been universalized to include the psychology of the girl. The authors argue that this crucial developmental phase for girls has uniquely feminine characteristics that have not been fully recognized or cohesively incorporated into psychoanalytic theories. This paper addresses these differences, which are based on characteristic patterns of object relationships, typical defenses, and social considerations. The authors argue that "female oedipal" is an oxymoron, and propose that this constellation be named "the Persephone complex" after the Greek myth of Persephone, which seems to capture better the typical situation of the little girl. They focus on the issue of separation and its complicated and necessary role in the triangular situation of females. Using illustrations from clinical material, the authors argue that the frequent appearance of separation material linked to triangular heterosexual competitive fantasies can and should be differentiated from material in which ideas about separation stem from dyadic and earlier issues. Misunderstanding how these separation conflicts tie into triangular "oedipal" relationships can lead to a "preoedipalization" of the dynamics of girls and women. PMID- 11212196 TI - Barbie and the tree of life: the multiple functions of gender in development. AB - Gender identity is the lens through which people experience being boy or girl, man or woman. It is a complex compromise formation that is not separate from the wishes, fears, and intrapsychic conflicts of other domains. Over the course of development, gender identity becomes layered and reconfigured. This paper looks at one child's experience of gender over several phases in her development in order to learn how gender is integrated into identity. At different times, as different conflicts came to the fore, she used gender to shape and lend definition to these conflicts. Conversely, her experiences in other spheres influenced her experience of gender. PMID- 11212197 TI - Separation-individuation phenomena in adulthood: general concepts and the fifth individuation. AB - The elaboration of separation-individuation theory in the years beyond childhood has been a psychoanalytic focus for several decades. In this paper, the nature of separation-individuation phenomena in adulthood and the terminology and controversy surrounding the use of the terms third, fourth, and fifth individuation are considered first; a detailed elaboration of the concept of the fifth individuation in late adulthood follows. PMID- 11212198 TI - The overstimulated state of dyslexia: perception, knowledge, and learning. AB - Dyslexia is far more than a learning disorder; it has significant impact on personality organization. While dyslexia usually begins to manifest most clearly in early latency when the challenge of learning to read is at its height, often the dyslexic child's ego development and functioning has already been adversely affected. The literature from neuropsychology suggests that dyslexia is a subtle language-processing disorder that affects emotional, cognitive, and social development. The neuroanatomical literature also suggests a significant correlation between the neurodevelopmental basis for dyslexia, the caregiving environment, and psychological development. These two bodies of literature and analytic observations of a dyslexic patient suggest that the dyslexic individual may have a neurological deficit that increases vulnerability to overstimulation. The author hypothesizes that emotional and cognitive states result and reappear within the analytic encounter. This complicates clinical assessment and technical decisions. The author presents an analytic case and examines (1) the impact of deficit on the development of conflict; (2) the impact of the overwhelmed ego on the mastery of developmental tasks; and (3) the impact of dyslexia on dysgnosia, transference, and analytic process and technique. PMID- 11212199 TI - Countertransference enactments informed by cancer in an analyst's child. AB - The author's son was diagnosed with Hodgkin's lymphoma in the spring of 1997. She traces the impact of this trauma on her practice, with specific emphasis on her experience as both analyst and mother, and on the related countertransference feelings and enactments. The paper discusses in detail the analyst's effort to determine for each patient whether or not to disclose the fact of her son's illness, the internal conflict she experienced over those decisions, and the effects of her decisions on her patients. An extensive case discussion focuses on a patient who appeared to intuit in a dramatic fashion the traumatic events in the analyst's private life. PMID- 11212200 TI - Infertility in the age of technology. AB - Rapid advances in medical and biological technologies are changing the ways we are born, live, and die. Biotechnology is pushing us in our notion of what is possible, and tapping into our most primitive omnipotent fantasies. For the most part these new techniques have not yet been integrated into a shared social consciousness. This paper examines, in a case study of a woman who eventually got pregnant with a donor egg and in a shorter case vignette, how the new technology impacts upon the analytic process. Attention is focused on the permeability of the boundaries between analyst and patient and between fantasy and action. The study shows how analyst and patient, together and often for the first time, must face the difficult moral and ethical issues stimulated by such procedures, as well as the anxieties and underlying fantasies they evoke. It is the uniqueness and the intensity of this experience that permeates boundaries, stimulates emotion in patient and analyst alike, and has the potential to deepen the analytic bond. The study underlines the need for the analyst to be flexible, moving back and forth between interpreting and creating a needed holding environment. Finally, the paper points out the tension between the traditional roles of motherhood, fatherhood, and family and those being created in this high tech world. PMID- 11212201 TI - The older patient in psychoanalysis. AB - The demographic shift toward extended longevity has led to a commensurate increase in the length of the working and productive years, and with it an increase in the number of so-called "older" patients who come into psychoanalysis or psychoanalytic psychotherapy. This led the Psychoanalytic Research and Development Fund to support a four-year study by a small group of experienced psychoanalysts of "the older patient in psychoanalysis." Aging and old age are considered to be the final developmental crisis of the successive epigenetic phases of the life cycle. Eleven case presentations and various briefer clinical vignettes informed us that older and even old individuals, who seek treatment themselves or who are appropriately referred, respond in a positive and effective fashion to psychoanalysis and psychoanalytic psychotherapy. As do younger patients in analysis, such older people, motivated by the wish to make the most of what time is left, become interested in understanding their pasts with respect to the present and the future. The life stories of two older men who undertook analysis, and the courses and outcomes of their analyses, illustrate our findings and impressions. In both cases conflicts and difficulties from earlier developmental phases, extending back even as far as the oedipal and preoedipal years, were revived during their older years. And although these conflicts might have been beyond definitive resolution, what is salient is the extent to which they were ameliorated: sufficiently that they did not impede a satisfactory adaptive solution of the final crisis of the normative sequences of the life cycle. PMID- 11212202 TI - Treatment of the older adult: the impact on the psychoanalyst. AB - Work with the elderly challenges analysts in special ways. The author presents clinical material from her practice and from investigative interviews with nine treating analysts who report personal reactions and countertransferences to analytic work with twelve elderly patients. She concludes that the major challenges in work with the elderly come more from the analyst than from the patients. Issues arising from the analyst's unresolved feelings about aging, parents, loss, and death are revived in the treatment of the elderly in an especially intense form. In this paper many aspects of transference are considered, especially those relating to illness, loss, and the problems that flow from identifications of the older analyst with the patient. The affective reverberations in younger and older analysts with regard to the initiation of analytic treatment, the inevitability of moving in and out of real life crises, the sustaining of loss, and, particularly, the impending termination, are presented in the paper. PMID- 11212203 TI - The exclusion of child psychoanalysis. PMID- 11212204 TI - Electrophysiological and pharmacological properties of the human brain type IIA Na+ channel expressed in a stable mammalian cell line. AB - The human brain voltage-gated Na+ channel type IIA alpha subunit was cloned and stably expressed in Chinese hamster ovary cells and its biophysical and pharmacological properties were studied using whole-cell voltage-clamp. Fast, transient inward currents of up to -8,000 pA were elicited by membrane depolarization of the recombinant cells. Channels activated at -50 mV and reached maximal activation at -10 mV to 0 mV. The reversal potential was 62 +/- 2 mV which is close to the Na+ equilibrium potential. The half-maximal activation and inactivation voltages were -24 +/- 2 mV and -63 +/- 1 mV, respectively. Currents were reversibly blocked by tetrodotoxin with a half-maximal inhibition of 13 nM. The effects of four commonly used anti-convulsant drugs were examined for the first time on the cloned human type IIA channel. Lamotrigine and phenytoin produced concentration- and voltage-dependent inhibition of the type IIA currents, whereas, sodium valproate and gabapentin (up to 1 mM) had no effect. These results indicate that recombinant human type IIA Na+ channels conduct tetrodotoxin-sensitive Na+ currents with similar properties to those observed in recombinant rat brain type IIA and native rat brain Na+ channels. This stable cell line should provide a useful tool for more detailed characterization of therapeutic modulators of human Na+ channels. PMID- 11212205 TI - Respiratory effects of stimulation of cell bodies of the A5 region in the anaesthetised rat. AB - To assess the importance of the pontine A5 region in modulating respiratory activity, electric current or microinjections of glutamate (10-30 nl, 1-3 nmol) were used to stimulate discrete zones within this region in the spontaneously breathing, anaesthetised rat. These stimuli evoked an expiratory facilitatory response, consisting of a decrease in respiratory rate (P < 0.01 electrical, P < 0.001 chemical) due to an increase of expiratory time (P < 0.01 in both cases) as measured from recordings of phrenic nerve activity. No changes were observed in inspiratory time. To avoid changes in PCO2, which could modulate the respiratory response, stimulation was also made during artificial ventilation. Under these conditions the expiratory facilitatory response elicited by glutamate was still present (P < 0.05), although its duration was reduced (P < 0.05), as was the magnitude of the phrenic burst (P < 0.05). At all the sites at which electrical stimulation and glutamate injection had evoked a respiratory response, electrical stimulation evoked a concomitant increase in both blood pressure and heart rate. Glutamate injection evoked a pressor response in 21 out of 30 animals. In eight animals the rise in blood pressure was followed by a fall in blood pressure and in one animal, a depressor response was observed. In all cases glutamate evoked an increase in heart rate. The expiratory facilitatory response was not evoked as a consequence of the increase of blood pressure since it was still present after the administration of guanethidine, which abolished the blood pressure changes. As glutamate is believed to excite perikarya rather than axons of passage these data indicate that expiratory facilitatory responses and the accompanying cardiovascular changes are the consequence of activating neurones located within the A5 region. The possible interactions between the A5 region and the medullary respiratory complex in eliciting these changes are discussed. PMID- 11212206 TI - Reorganisation of respiratory network activity after loss of glycinergic inhibition. AB - gamma-Aminobutyric acid (GABA)-ergic and glycinergic inhibition is believed to play a major role in the respiratory network. In the present study we tested whether specific blockade of glycinergic inhibition resulted in changes in respiratory network interaction and function. Using the working heart-brainstem preparation from adult mice, we recorded phrenic nerve activity and the activity of different types of respiratory neurones located in the ventrolateral medulla. Strychnine (0.03-0.3 microM) was given systemically to block glycine receptors (Gly-R). During exposure to strychnine, post-inspiratory (PI) neurones shifted their onset of discharge into the inspiratory phase. As a consequence, the post inspiratory phase failed and the rhythm changed from a three-phase cycle (inspiration, post-inspiration, expiration, with a frequency of about. 0.24 Hz) to a faster, two-phased cycle (inspiration expiration, frequency about 0.41 Hz). Inspiratory and expiratory neurones altered their augmenting membrane potential pattern to a rapidly peaking pattern. Smaller voltage oscillations at approximately 10 Hz and consisting of excitatory and inhibitory postsynaptic potential sequences occurred during the expiratory interval. Due to their high frequency and low amplitude, such oscillations would be inadequate for lung ventilation. We conclude that, under physiological conditions, glycinergic inhibition does indeed play a major role in the generation of a normal respiratory rhythm in adult mice. After failure of glycinergic inhibition a faster respiratory rhythm seems to operate through reciprocal GABAergic inhibition between inspiratory and expiratory neurones, while phase switching is organised by activation of intrinsic membrane properties. PMID- 11212207 TI - Erg1, erg2 and erg3 K channel subunits are able to form heteromultimers. AB - Clonal somato-mammotroph GH3/B6 cells and lactotroph MMQ cells express two (ergl, erg2) of the three cloned rat ether-a-go-go-related gene (erg) K channel subunits. To study whether the erg subunits form heteromultimers, dominant negative mutants of erg and erg2 were constructed by point mutation (erg1G630S, erg2G480S). After co-expression of these mutants with the wild-type erg1, erg2, or erg3 in Chinese hamster ovary (CHO) cells no erg currents could be detected. In contrast, in co-expression experiments with members of the other ether-a-go-go (EAG) subfamilies (eagl, elkl) the mutant erg1G630S had no effect. These results strongly suggest that erg channel subunits are able to form heteromultimers within the erg channel subfamily. Suppression of the endogenous E-4031-sensitive currents in GH3/B6 and MMQ cells by erg1G630S confirms that they are mediated by erg channels despite the differences in gating kinetics in these cells. Reduction of the erg current in GH3/B6 cells by erg2G480S indicates that erg heteromultimers can also be formed in these cells. PMID- 11212208 TI - Inhibitors of the Cl-/HCO3- exchanger activate an apical anion conductance with similar features in the epithelial cells of rabbit gallbladder: analysis in intact epithelium. AB - In the apical plasma membrane of rabbit gallbladder epithelium, hydrochlorothiazide (HCTZ), besides its inhibiting action on Na+-Cl- symport and some side-effects, opens a SITS-sensitive Cl- conductance (Gcl), resulting in depolarization of the membrane due to a cell-to-lumen Cl- backflux. Some previous indications suggest that GCl is someway related to the Cl-/HCO3- exchanger. Thus the actions on the apical membrane of HCTZ and two inhibitors of the exchanger mainly studied in erythrocytes, namely phlorizin and phenylglyoxal (PG), have been compared. The transapical Cl- influx was measured radiochemically and the anion exchange fraction identified. The apical and transepithelial membrane potentials (Vm, Vm), the apical/basolateral membrane resistance ratio (Rm/Rs) and the transepithelial resistance (Rep) were measured with conventional microelectrodes and the changes in apical electromotive force and conductance were calculated. It has been shown that: (1) 2.5 x 10(-4) mol/l HCTZ abolishes Cl /HCO3- exchange in a few seconds, (2) exchanger inhibition by HCTZ is direct and not mediated by carbonic anhydrase inhibition, (3) 2 mmol/l phlorizin and 4 mmol/l PG also inhibit the exchanger in a few seconds or at least rapidly and in parallel activate a depolarization of 6-7 mV, like HCTZ, (4) dose/response curves of the three drugs for depolarization activation and anion exchange inhibition overlap, (5) depolarization time courses are similar for the three drugs, (6) a decrease in the Rm/Rs ratio occurs in the presence of the three drugs, with a significant change in apical electromotive force when the luminal Cl- concentration is reduced, all this indicating the appearance of a substantial, quantifiable GCl which is absent in the absence of incubation with the drugs, (7) GCl values are similar, regardless of the drug which generates them, (8) the effects of the three drugs are not additive, and (9) stilbenes and dipyridamole abolish GCl (but not DPC) as well as the basal intrinsic conductance of the exchanger. On this basis it is concluded that some inhibitors of the Cl-/HCO3- exchanger either turn it into an anion channel or, less probably, activate a parallel GCl, as a consequence of the exchanger inhibition. PMID- 11212209 TI - Inhibitors of the Cl-/HCO3- exchanger activate an anion channel with similar features in the epithelial cells of rabbit gallbladder: patch-clamp analysis. AB - The stilbene- and dipyridamole-sensitive Cl-conductance (GCl), non-additively activated by some inhibitors of the Cl-/HCO3- exchanger (hydrochlorothiazide, phlorizin, phenylglyoxal) after the exchanger inhibition in the apical plasma membrane of rabbit gallbladder epithelium, has been investigated by patch-clamp technique with cell-attached and inside-out configurations. No Cl- channels were observed under basal conditions or after treatment with 2.5 x 10(-4) mol/l 8-Br cAMP or hydrochlorothiazide (HCTZ) on the cytosolic side. Conversely, with 2.5 x 10(-4) mol/l HCTZ or 2 mmol/l phlorizin in the pipette, a non-rectifying Cl- channel with about 5 pS conductance and 0.3-0.4 voltage-independent open probability was observed; it was inhibited by 10(-4) - 5 x 10(-4) mol/l SITS, 10( 4) mol/l furosemide or 0.6 x 10(-4) mol/l dipyridamole; the effects of HCTZ and phlorizin were not additive. Open probability increased from 0 (after seal formation) to a maximum of 0.3-0.4 reached in 7-9 min. Similar results were obtained with both configurations. With the cell-attached configuration, HCTZ added to the bath did not activate Cl- channels in the patch. The channel was shown to exclude cations, to be selective for Cl-, but also conductive for gluconate (PGluc/PCl = 0.18). On this basis, it is concluded that: (1) GCl, activated either by HCTZ or phlorizin, has the same underlying anion channels, (2) the channels can be activated only on the external side of the membrane, also in the absence of cytoplasm, without cellular mediations or effects at a distance along the membrane, (3) the channels are inhibited by the same drugs which inhibit the very small intrinsic anion conductance of the exchanger, (4) they are either related to a slow conversion of inhibited exchangers into channels or, less probably, they are parallel to the exchanger and slowly activated by intra membrane (or membrane-bound) mediators in their turn activated by near, inhibited exchangers. PMID- 11212210 TI - Functional expression of angiotensin II receptors in type-I cells of the rat carotid body. AB - Angiotensin II increases afferent discharge from the carotid body in vitro. We hypothesized that angiotensin II receptors (AT receptors) are expressed functionally in the type-I cell of the carotid body. Cytosolic free [Ca2+] ([Ca2+]i) in type-I cells freshly dissociated from rat carotid bodies was measured spectrofluorimetrically. Angiotensin II (10-100 nM) concentration dependently increased [Ca2+]i in type-I cells. The [Ca2+]i response was blocked by pretreatment with losartan (1 microM), an AT1 receptor antagonist, but not by blockade of AT2 receptors with PD- 123319 (1 microM). Moreover, the gene expression of AT1 receptors was assessed by the reverse transcriptase polymerase chain reaction and gene transcripts of both AT1a and AT1b receptors were detected in the carotid body. In addition, immunohistochemical study revealed that AT1 immunoreactivity was localized in lobules of type-I cells in the carotid body. Taken together, these results suggest that type-I cells in the rat carotid body express functional angiotensin II receptors. The binding of angiotensin II to the AT1 receptors increases [Ca2+]i, a key step of the intracellular signalling cascade following the activation of the receptors. It is concluded that angiotensin II modulates carotid body chemoreceptor function directly via AT1 receptors in the type-I cell. PMID- 11212211 TI - Tissue distribution and functional expression of the human voltage-gated sodium channel beta3 subunit. AB - This study investigated the distribution of beta3 in human tissues and the functional effects of the human beta3 subunit on the gating properties of brain and skeletal muscle alpha subunits. Using RT-PCR of human cDNA panels, beta3 message was detected in brain, heart, kidney, lung, pancreas and skeletal muscle. Both alphaIIA and SkM1 expressed in Xenopus oocytes inactivated with a time course described by two exponential components representing fast and slow gating modes, while co-expression of human beta3 with alphaIIA or SkM1 significantly increased the proportion of channels operating by the fast gating mode. In the presence of beta3 a greater proportion of alphaIIA or SkM1 current was described by the fast time constant for both inactivation and recovery from inactivation. beta3 caused a hyperpolarizing shift in the voltage dependence of inactivation of alphaIIIA and reduced the slope factor. The voltage dependence of inactivation of SkM1 was described by a double Boltzmann equation. However, SkM1 co-expressed with beta3 was described by a single Boltzmann equation similar to one of the Boltzmann components for SkM1 expressed alone, with a small positive shift in V1/2 value and reduced slope factor. This is the first study demonstrating that beta3 is expressed in adult mammalian skeletal muscle and can functionally couple to the skeletal muscle alpha subunit, SkM1. PMID- 11212212 TI - The properties of the secretagogue-evoked chloride current in mouse pancreatic acinar cells. AB - In this paper we describe the properties of the secretagogue-evoked chloride current from mouse pancreatic acinar cells. Single cells were patch-clamped in the whole-cell configuration with solutions that excluded cation currents and then stimulated with 1 mM carbachol (CCh). This resulted in a current that rose to a peak and then decayed to a plateau level. The current/voltage relationship of the peak current was linear whereas that of the plateau phase was rectified and showed time and voltage dependence. To determine if the CCh evoked current was strictly Ca2+ dependent, we compared the properties of the plateau current with those of currents evoked by directly raising cytosolic [Ca2+] The properties of the two currents were the same, with both currents showing outward rectification, development at depolarised potentials, similar time constants of activation, permeability sequences and sensitivity to the Cl- channel inhibitor 4,4'-diisothiocyanatodihydrostilbene-2,2'-disulphonic acid (DIDS). We conclude that the agonist-evoked rise in Ca2+ is alone a sufficient signal to activate the CL- current. PMID- 11212213 TI - Weight loss reduces expression of SREBP1c/ADD1 and PPARgamma2 in adipose tissue of obese women. AB - Weight loss in obese patients, even if moderate, is clearly beneficial for health and implies a reduction in either adipocyte number or volume. This can be regulated by the key adipose transcription factors, sterol-regulatory-element binding protein-1c/adipocyte differentiation and determination factor-1 (SREBP1c/ADD1), peroxisome proliferator-activated receptor-gamma2 (PPARgamma2) and CCAAT-enhancer binding protein-alpha (C/EBPalpha). which regulate the adipocyte metabolism and differentiation process. The present study was undertaken to obtain insights into the expression of these transcription factors during moderate weight loss in humans. In addition, the adipose depot-related differences and the relation to adipose lipoprotein lipase (LPL) expression and plasma lipids were studied. Using quantitative reverse transcription polymerase chain reaction (RT-PCR), the total amount of each adipose transcription factor messenger ribonucleic acid (mRNA) was determined in the subcutaneous or omental adipose tissue after a controlled, 2-month, bodyweight-reduction trial in 11 obese middle-aged women and 17 comparable obese controls. Weight loss (6% of body weight) was associated with reduced serum insulin and plasma triacylglycerols. Adipose tissue PPARgamma2 and SREBP1c/ADD1 mRNA were lower in the weight-loss group than in controls (by 30% and 28%, respectively), whereas the C/EBPalpha mRNA level did not change. Moreover, PPARgamma2 mRNA was lower only in the subcutaneous adipose depot and was related to both adipose tissue lipoprotein lipase (LPL) mRNA and improvement in plasma triacylglycerols in the weight-loss group. Our results suggest a functional role for SREBP1c/ADD1 and PPARgamma2 in the control of energy metabolism in human adipose tissue. PMID- 11212214 TI - Non-uniform mapping of stress-induced, motility-related charge movement in the outer hair cell plasma membrane. AB - There is a growing consensus that outer hair cell (OHC) electromotility underlies the mammalian cochlear amplifier. This voltage-dependent motility is mirrored by a gating current, which along with motility can be altered by tension applied to the cell's plasma membrane. We used localized tension application along the length of the OHC to induce gating currents from membrane microdomains; with this information we mapped the distribution of the OHC's sensitivity to membrane stress before and after disrupting the cytoskeleton with intracellular Pronase. Mechanically induced gating currents, which were susceptible to salicylate, lanthanides and turgor pressure, evidenced a bell-shaped distribution that was restricted to the lateral membrane where the electromotile response resides. After Pronase treatment, gating currents remained intact and restricted. These results confirm that the molecular motors are intrinsically and bi-directionally susceptible to voltage and tension, and provide evidence for limited mobility of OHC motors within the cell's lateral membrane. PMID- 11212215 TI - Contribution of angiotensin II, endothelin 1 and the endothelium to the slow inotropic response to stretch in ferret papillary muscle. AB - We investigated the contribution of angiotensin II and endothelin I to the slow positive inotropic response observed following stretch of isolated ferret papillary muscle from 88% to 98% of the length at which maximum force is generated. Angiotensin antagonists losartan and saralasin did not affect the magnitude of the slow response in ferret papillary muscle. The ETA-selective antagonist BQ123 slightly reduced the magnitude of the slow response (P > 0.05). In the presence of PD145065 (an ETA and ETB antagonist), the magnitude of the slow response was reduced significantly by 50%. Removal of the endothelium with 1% Triton X-100 reversed the slow response to stretch. We conclude that, in the ferret, endothelin I acting through ETA and ETB receptors, contributes to the slow response although it is not the sole mediator. Angiotensin II is not a prerequisite for the slow response to stretch. We have shown for the first time that the endocardial endothelium plays a pivotal role in this phenomenon in cardiac papillary muscle. PMID- 11212216 TI - Functional rescue of defective mutant connexons by pairing with wild-type connexons. AB - We have compared the functional and structural integrity of gap junction channels assembled from a Cx45 truncation mutant with those of gap junction channels assembled from wild-type (wt) Cx45 and Cx43. These channel-forming proteins are constitutively expressed in HeLa cells. The truncation mutant lacks the last 26 amino acids of the COOH-terminus, including nine serine phosphorylation sites that are associated with regulatory processes of these channels. We determined the presence of gap junction plaques in these cells with the immunogold freeze fracture technique, which showed that plaque formation is similar in all the clones investigated. Junctional permeability was probed with calcein transfer and flow cytometry analyses and junctional conductance was measured in cell pairs with double whole-cell patch-clamp techniques. For homotypic pairing only the truncated mutant did not form permeable channels. However, coupling was restored for heterotypic channels (pairing wtCx45- or wtCx43- with mutant-connexons), whose junctional communication was not different from that of the homotypic channels. Our results indicate that the presence of gap junction plaques does not warrant functional coupling and that heterotypic trCx45/wtCx45 channels can be regulated by the intact wtCx45 connexons. This dominant-positive effect is also operative when wtCx43 are paired with trCx45 connexons. PMID- 11212217 TI - Identification of an organic anion transport system in the human colon carcinoma cell line HT29 clone 19A. AB - The human colon carcinoma cell line HT29 c1.19A was studied for organic anion transporter activity by determining intracellular fluo-3 and fura-red accumulation and by measuring fluo-3 efflux. Modulators of organic anion transport systems were used to identify the transporters that are involved in dye extrusion. Addition of probenecid to the dye-loading medium, containing 10 microM fluo-3/AM and fura-red/AM, resulted in a dose-dependent increase in fluo-3 and fura-red accumulation in the cells. The increase in fluo-3 accumulation in the cells in the presence of probenecid was explained by the inhibitory effect of this compound on fluo-3 efflux. Fluo-3 efflux from the cells was also inhibited by sulfinpyrazone, another inhibitor of organic anion transport. Substrates of renal probenecid-sensitive organic anion exchange mechanisms as well as modulators of multidrug resistance associated protein (MRP) activity did not influence fluo-3 extrusion rates. However, reducing intracellular ATP contents completely blocked fluo-3 extrusion. Moreover, MK571, an inhibitor of MRP, significantly stimulated dye accumulation, whereas inhibitors of the multidrug resistance gene (MDR1) product Pglycoprotein, cyclosporin A and verapamil, did not. As probenecid inhibits fluo-3 efflux across the apical membrane of cells grown on permeable supports, we conclude that a probenecid-sensitive organic anion transporter is present in the apical membrane of HT29 c1.19A cells. This organic anion transport system differs from MDRI and MRP2. PMID- 11212218 TI - The energy cost of walking in children. AB - Size, morphology and motor skills change dramatically during growth and this probably has an effect on the cost of locomotion. In this study, the effects of age and speed on the energy expended while walking were determined during growth. The rate of oxygen consumption and carbon dioxide production were measured in 3- to 12-year-old children and in adults while standing and walking at different speeds from 0.5 m x s(-1) to near their maximum aerobic walking speed. Standing energy expenditure rate decreases with age from 3.42 +/- 0.48 W x kg(-1) (mean +/ SD, n = 6) in the 3- to 4-year-olds to 1.95 +/- 0.22 W x kg(-1) (n = 6) in young adults. At all ages the gross cost of transport has a minimum which decreases from 5.9 J x kg(-1) x m(-1) in 3- to 4-year-olds to 3.6 J x kg(-1) x m(-1) after 10 years of age. The speed at which this minimum occurs increases from 1.2 m x s( 1) to 1.5 m x s(-1) over the same age range. At low and intermediate walking speeds the net cost of transport is similar in children and adults (about 2 J x kg(-1) x m(-1)). In young children walking at their highest speeds the net cost of transport is 70% (3- to 4-year-olds) to 40% (5- to 6-year-olds) greater than in adults. PMID- 11212219 TI - Apamin interacts with all subtypes of cloned small-conductance Ca2+-activated K+ channels. AB - The purpose of the present study was to examine how apamin interacts with the three cloned subtypes of small-conductance Ca2+-activated K+ channels (hSK1, rSK2 and rSK3). Expression of the SK channel subtypes in Xenopus laevis oocytes resulted in large outward currents (0.5-5 microA) after direct injection of Ca2+. In all three cases the Ca2+-activated K+ currents could be totally inhibited by 500 nM apamin. Dose-response curves revealed a subtype-specific affinity for the apamin-induced inhibition with IC50 values of 704 pM and 196 nM (biphasic) for hSK1, 27 pM for rSK2 and 4 nM for rSK3. Consistent with these results, membranes prepared from oocytes expressing the SK channel subtypes bound 125I-labelled apamin with distinct dissociation constants (Kd values) of approx. 390 pM for hSK1, 4 pM for rSK2 and 11 pM for rSK3. These results show that apamin binds to and blocks all three subtypes of cloned SK channels, and the distinct values for IC50 and Kd suggest that apamin may be useful for determining the expression pattern of SK channel subtypes in native tissue. PMID- 11212220 TI - Chloride conductance and volume-regulatory nonselective cation conductance in human red blood cell ghosts. AB - To identify the ion channels involved in erythrocyte volume regulation, whole cell currents from human red blood cells (RBCs) were recorded in isotonic, hypotonic and hypertonic media. In isotonic NaCl bath solution, whole-cell currents rectified outwardly with reversal potentials (Vrev) between the equilibrium potential of Cl- (ECl) and that of nonselective cations (NSC), ENSC. Replacement of bath Cl by gluconate decreased outward conductance (G outward) by 43 +/- 6% (n = 5) and shifted Vrev with ECl indicating a high fractional Cl- conductance. Hypotonic cell swelling reversibly decreased G outward by 23 +/- 3% (n = 8) while hypertonic cell shrinkage reversibly increased G outward by 27 +/- 8% (n = 5). These shrinkage-activated and swelling-inactivated current fractions rectified outwardly with Vrev at ENSC suggesting that both fractions are generated by the same type of NSC channel. The shrinkage-activated deltaG outward decreased from 4.7 +/- 1.2 nS (n = 3) to 1.4 +/- 0.4 nS (n = 5) and 0.5 +/- 0.4 nS (n = 7) with the increase of pipette [Cl-] from 7 mM to 39 mM and 139 mM, respectively. Similarly, with this increase of pipette [Cl-], G outward under isotonic control conditions decreased from 8.2 +/- 1.4 nS (n = 5) to 7.4 +/- 1.0 nS (n = 20) and 4.1 +/- 0.7 nS (n = 17), due to the differing activity of these NSC channels. In conclusion, human RBCs express, besides a high fractional Cl- conductance, NSC channels that are regulated by cell volume and the cytosolic [Cl ]. PMID- 11212222 TI - New perspectives in breath-by-breath determination of alveolar gas exchange in humans. AB - Alveolar gas transfer over a given breath (i) was determined in ten subjects at rest and during steady-state cycling at 60, 90 or 120 W as the sum of volume of gas transferred at the mouth plus the changes of the alveolar gas stores. This is given by the gas fraction (FA) change at constant volume plus the volume change (deltaVAi) at constant fraction i.e. VAi-1(FAi-FAi-1)+FAi x deltaVAi, where VAi-1 is the end-expiratory volume at the beginning of the breath. These quantities, except for VAi-1, can be measured on a single-breath (breath-by-breath) basis and VAi-1 set equal to the subject's functional residual capacity (FRC, Auchincloss model). Alternatively, the respiratory cycle can be defined as the interval elapsing between two equal expiratory gas fractions in two successive breaths (Gronlund model G). In this case, Ft1 = Ft2 and thus the term VAi-1 (FAi-FAi-1) vanishes. In the present study, average alveolar O2 uptake (VO2,A) and CO2 output (VCO2,A) were equal in both approaches whereby the mean signal-to-noise ratio (S/N) was 40% larger in G. Other approaches yield steady state S/N values equal to that obtained in G, although they are based on the questionable assumption that the inter-breath variability of alveolar gas transfer is minimal. It is concluded that the only promising approach for assessing "true" single-breath alveolar gas transfer is that originally proposed by Gronlund. PMID- 11212221 TI - Spermine increases the active and passive transport across the alveolar epithelium in situ: effect of thiol reagents. AB - An intact alveolar epithelial barrier is thought to be important for alveolar liquid absorption. However, polycations increase alveolar permeability without affecting alveolar liquid absorption (Saumon et al., Am J Physiol 1995: 269:L185 L194). We have reconsidered this issue using polyamines. The polyamine spermine (10(-3) mol/l) produced a large (up to 20-fold), sustained increase in the permeability of the alveolar barrier to mannitol (PAMan) and in alveolar liquid absorption (Jw, twofold) in isolated rat lungs. These increases were inhibited by 5 x 10(-3) mol/l putrescine and 2 x 10(-3) mol/l spermidine. Because spermine is known to affect the phosphoinositide/Ca2+ signalling pathway, we evaluated the effects of thiol reagents known to interfere with this pathway in different ways. Thimerosal, a thiol reagent which sensitizes the inositol 1,4,5-trisphosphate (IP3) receptor, inhibited the spermine-induced increase in PA(Man) and, to a lesser extent, that of Jw. Mersalyl, a thiol reagent which blocks IP3-gated Ca2+ channels, enhanced spermine's effect, whereas N-ethylmaleimide, a non-specific thiol reagent, had no effect. These observations show that large increases in permeability may coexist with increases in Jw. They also suggest that the phosphoinositide/Ca2+ second messenger pathway is involved in modulating the tightness of the alveolar barrier and alveolar liquid absorption. PMID- 11212223 TI - Inducible nitric oxide synthase (iNOS) is expressed similarly in multiple aberrant crypt foci and colorectal tumors from the same patients. AB - Aberrant crypt foci (ACF) are the earliest identified neoplastic lesions in the colon. Aberrant expression of inducible nitric oxide synthase (iNOS or NOS2) has been documented in colorectal tumors, but expression of iNOS has not been reported in human ACF or multiple neoplastic lesions from the same patient. Immunohistochemical expression of iNOS was evaluated in 42 ACF, 14 adenomas, and 25 carcinomas and their adjacent normal mucosa. iNOS was strongly expressed in the normal colonic epithelial cells of all patients; it was markedly reduced in 21 of 42 (50%) ACF and in 14 of 25 (56%) carcinomas. The expression of iNOS was remarkably similar in multiple lesions from the same patient (P < 0.0001). These results suggest that the reduced expression of iNOS is a very early event in the development of some human colorectal tumors, and that host factors control the expression of iNOS similarly in premalignant and malignant colonic epithelial cells. PMID- 11212224 TI - Altered expression of androgen receptor in the malignant epithelium and adjacent stroma is associated with early relapse in prostate cancer. AB - The molecular basis of androgen-independent prostate cancer is unknown; however, functional androgen receptor (AR) signaling is maintained after the acquisition of hormone-refractory disease. Because normal and malignant prostate epithelial cell proliferation is regulated by androgen stimulation via both the AR-positive stroma and epithelium, we sought to evaluate patterns of AR expression in these cells and to determine any relationships with prostate cancer progression. AR expression in the malignant epithelium and associated periepithelial and nonperiepithelial stroma was measured in a cohort of 96 patients with clinically localized prostate cancer treated with radical prostatectomy. Data were evaluated for disease relapse using the Kaplan-Meier method and in a Cox proportional hazards model with other variables of known clinical relevance, including Gleason score, pathological stage, clinical stage, and pretreatment prostate-specific antigen concentration. Concurrent overexpression of AR (> or = 70% positive nuclei) in the malignant epithelium and loss of AR immunoreactivity in the adjacent periepithelial stroma (< or = 30%) was associated with higher clinical stage (P = 0.01), higher pretreatment prostate-specific antigen level (P = 0.03), and earlier relapse after radical prostatectomy (log-rank P = 0.009). These data identify a pattern of AR expression in malignant epithelium and adjacent stroma that is associated with a poor clinical outcome in prostate cancer. Equally important, they identify the need to further investigate the mechanistic basis of loss of AR expression in the malignant stroma and its potential role in deregulation of prostate epithelial cell proliferation. PMID- 11212225 TI - Persistent genetic instability in cancer cells induced by non-DNA-damaging stress exposures. AB - A hallmark of cancer cells is their pronounced genetic instability, which has been implicated in both tumor development and negative treatment outcomes. Recently, it has been reported that ionizing radiation may induce a persistent state of hypermutability in mammalian cells that lasts for many (>30) cell divisions. In this study, we examined whether other stress signals (both DNA damaging non-DNA-damaging) can initiate a similar process. We show that persistent genetic instability was induced by nongenotoxic stress exposures such as heat treatment, serum starvation, or the tumor microenvironment, as well as genotoxic stresses such as ionizing radiation and exposure to hydrogen peroxide. Progeny of 10-20% of surviving cells exhibited persistent and pronounced genetic instability at both an artificially transfected gene and a genomic minisatellite locus 23 cell divisions after the initial exposure. Stress-induced persistent genetic instability may be a general response of tumor cells to a wide range of genotoxic or nongenotoxic stress conditions. PMID- 11212226 TI - Assessment of tumor necrosis factor receptor and Fas signaling pathways by transcriptional profiling. AB - Apoptosis, or programmed cell death, is an important mechanism by which cells are eliminated during immune regulation and embryonic development. Aberrations in the signaling pathways leading to apoptosis may result in cancer, autoimmune diseases, or inflammatory disorders. In view of this, an understanding of the signaling capabilities of apoptosis-inducing or death receptors is essential to understanding their roles in biology and disease. We used cDNA microarrays to examine the downstream transcriptional effects of two members of the tumor necrosis factor (TNF) family of death receptor ligands. We compared the transcriptional responses of a model colon cancer cell line, HT29, to TNF-alpha and anti-Fas activating antibody. Both ligands induced a subset of genes characteristic of activation of the transcription factor nuclear factor-kappaB (NF-kappaB). Follow-up analyses demonstrated that, although TNF-alpha activated NF-kappaB through IkappaB-alpha degradation, alpha-Fas treatment led to NF-kappaB activation through a mechanism distinct from IkappaB-alpha degradation. PMID- 11212227 TI - A novel response of cancer cells to radiation involves autophagy and formation of acidic vesicles. AB - The mechanisms underlying neoplastic epithelial cell killing by ionizing radiation are largely unknown. We discovered a novel response to radiation manifested by autophagy and the development of acidic vesicular organelles (AVO). Acidification of AVO was mediated by the vacuolar H+-ATPase. Staining with the lysosomotropic agent acridine orange enabled us to quantify AVO accumulation and to demonstrate their time- and dose-dependent appearance. The appearance of AVO occurred in the presence of the pan-caspase inhibitor z-Val-Ala-Asp(Ome) fluoromethyl ketone, but was inhibited by 3-methyladenine, an inhibitor of autophagy. The accretion of AVO in surviving progenies of irradiated cells, and the increased incidence of clonogenic death after inhibition of vacuolar H+ ATPase suggest that formation of acidic organelles represents a novel defense mechanism against radiation damage. PMID- 11212228 TI - Absence of endothelial cells, central necrosis, and fibrosis are associated with aggressive inflammatory breast cancer. AB - We recently established a new human inflammatory breast cancer (IBC) xenograft (WIBC-9) originating from a patient with IBC. The graft was transplantable in BALB/c nude and severe combined immunodeficient (SCID) mice. WIBC-9 was frequently accompanied by lung metastasis and exhibited erythema of the overlying skin, reflecting its human counterpart. Histological study of the original tumor and WIBC-9 revealed invasive ductal carcinoma with a hypervascular structure of solid nests and marked lymphatic permeation in the overlying dermis. In the central part of the solid nests, absence of endothelial cells, central necrosis, and fibrosis were observed. In vitro, WIBC-9 formed tube-like structures and loops, reflecting its in vivo feature and its human counterpart. WIBC-9 exhibited aneuploidy, ErbB-2 gene amplification, and an absence of estrogen receptor and progesterone receptor, which is consistent with IBC. Comparative studies of WIBC 9, three established non-IBC xenografts, and a human breast cancer cell line (SK BR3) by reverse transcription-PCR, ELISA, and immunohistochemistry indicated that certain human genes (interleukin 8, vascular epidermal growth factor, basic fibroblast growth factor, angiopoietin 13, Flt-1, Tie-2, and Tie-1) and certain murine genes (integrin alpha(v)beta3, flt-1, tie-2, vascular epidermal growth factor, and CD31) were overexpressed in exposure to tumor cells. The molecular basis and these unique histological features may be associated with aggressive IBC on angiogenic and nonangiogenic pathways. PMID- 11212229 TI - Coexpression of CD40 and CD40 ligand in cutaneous T-cell lymphoma (mycosis fungoides). AB - Microarray analysis is a promising new approach for creating specific expression profiles of multiple genes simultaneously. We quantitatively analyzed differential gene expression patterns in mycosis fungoides-derived clonal T cells and autologous, identically cultured CD4+ lymphocytes using microarrays containing 588 cDNA segments from genes relevant to cell signaling, carcinogenesis, and apoptosis. Among other dissimilarities, neoplastic T cells showed coexpression of CD40 (Bp50) and CD40 ligand (gp39, CD154). These results could be corroborated by reverse transcription-PCR, immunohistochemistry, and two color immunofluorescence staining. Our data suggest that in cutaneous T-cell lymphoma, CD40/CD40 ligand interactions might represent a paracrine loop that is crucial not only in preventing apoptosis or positively regulating growth but also in homing of neoplastic cells to the skin. PMID- 11212230 TI - Cadmium-induced malignant transformation of human prostate epithelial cells. AB - Prostate cancer has become epidemic, and environmental factors such as cadmium may be partly responsible. This study reports malignant transformation of the nontumorigenic human prostatic epithelial cell line RWPE-1 by in vitro cadmium exposure. The cadmium-transformed cells exhibited a loss of contact inhibition in vitro and rapidly formed highly invasive and occasionally metastatic adenocarcinomas upon inoculation into mice. The transformed cells also showed increased secretion of MMP-2 and MMP-9, a phenomenon observed in human prostate tumors and linked to aggressive behavior. Cadmium-induced malignant transformation of human prostate epithelial cells strongly fortifies the evidence for a potential role of cadmium in prostate cancer. PMID- 11212231 TI - Antitumor immunity induced by laser immunotherapy and its adoptive transfer. AB - The ideal cancer treatment modality should not only cause tumor regression and eradication but also induce a systemic antitumor immunity, which is essential for control of metastatic tumors and for long-term tumor resistance. Laser immunotherapy using a laser, a laser-absorbing dye, and an immunoadjuvant has induced such long-term immunity in treatment of a mammary metastatic tumor. The successfully treated rats established total resistance to multiple subsequent tumor challenges. To further study the mechanisms of the antitumor immunity induced by this novel treatment modality, passive adoptive transfer was performed using splenocytes as immune cells. The spleen cells that were harvested from successfully treated tumor-bearing rats provided 100% immunity in the naive recipients. The passively protected first cohort rats were immune to tumor challenge with an increased tumor dose; their splenocytes also prevented the establishment of tumor in the second cohort of naive recipient rats. This immunity transfer was accomplished without the usually required T-cell suppression in recipients. PMID- 11212232 TI - RB2/p130 gene-enhanced expression down-regulates vascular endothelial growth factor expression and inhibits angiogenesis in vivo. AB - Angiogenesis is an essential step in the progression of tumor formation and development. The switch to an angiogenetic phenotype can occur as a distinct step before progression to a neoplastic phenotype and is linked to genetic changes such as mutations in key cell cycle regulatory genes. The pathogenesis of the angiogenetic phenotype may involve the inactivation of tumor suppressor genes such as the "guardian of the genome," p53, and the cyclin-dependent kinase inhibitor p16. Retinoblastoma family member RB2/p130 encodes a cell cycle regulatory protein and has been found mutated in different tumor types. Overexpression of RB2/p130 not only suppresses tumor formation in nude mice but also causes regression of established tumor grafts, suggesting that RB2/p130 may modulate the angiogenetic balance. We found that induction of RB2/p130 expression using a tetracycline-regulated gene expression system as well as retroviral and adenoviral-mediated gene delivery inhibited angiogenesis in vivo. This correlated with pRb2/p130-mediated down-regulation of vascular endothelial growth factor protein expression both in vitro and in vivo. PMID- 11212233 TI - Interferon gamma-dependent induction of thymidine phosphorylase/platelet-derived endothelial growth factor through gamma-activated sequence-like element in human macrophages. AB - Thymidine phosphorylase (TP), an enzyme involved in the reversible conversion of thymidine to thymine, is identical to platelet-derived endothelial cell growth factor. TP expression in cancer cells and/or infiltrated macrophages is associated with microvessel density and poor clinical prognosis in patients with various tumor types. However, how TP expression is up-regulated in human tumors is unclear. Of various inflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha), interleukin 1 alpha (IL-1alpha), and interferon gamma (IFN gamma), we observed that IFN-gamma most effectively increased the expression of TP in cultured human monocytic U937 cells. Transient transfection of the various deletion constructs of the TP promoter showed that the presence of the -474 to 355 sequence containing gamma-activated sequence-like element was essential for IFN-gamma-dependent activation of the TP gene. Furthermore, the IFN-gamma dependent transcriptional activity of the promoter construct containing mutations in the gamma-activated sequence-like element was significantly decreased. An electrophoretic mobility shift assay showed that IFN-gamma increased signal transducers and activators of transcription 1 binding to gamma-activated sequence like element in the TP promoter. IFN-gamma could be a mediator of TP expression in infiltrated monocyte/macrophages, and those monocyte/macrophages expressing TP might play an important role in malignancy and angiogenesis in various human tumors. PMID- 11212234 TI - Synthetic protein transduction domains: enhanced transduction potential in vitro and in vivo. AB - The protein transduction domain (PTD) embedded in the HIV TAT protein (amino acids 47-57) has been shown to successfully mediate the introduction of heterologous peptides and proteins in excess of Mr 100,000 into mammalian cells in vitro and in vivo. We report here that the modeled structure of the TAT PTD is a strong amphipathic helix. On the basis of this information, we synthesized a series of synthetic PTDs that strengthen the alpha-helical content and optimize the placement of arginine residues. Several PTD peptides possessed significantly enhanced protein transduction potential compared with TAT in vitro and in vivo. These optimized PTDs have the potential to deliver both existing and novel anticancer therapeutics. PMID- 11212235 TI - Soluble recombinant endostatin purified from Escherichia coli: antiangiogenic activity and antitumor effect. AB - Endostatin is a potent and specific antiangiogenic protein capable of inhibiting the growth of murine and xenotransplanted human tumors. Thus far, however, recombinant endostatin prepared from Escherichia coli is insoluble after purification and therefore inappropriate for clinical settings. A soluble form of endostatin is available from a yeast system with relatively low yield and high cost, which has made it difficult to produce endostatin in quantities sufficient for extensive clinical evaluation. In this study, we developed a protocol to generate soluble recombinant murine endostatin from E. coli at a yield of 150 mg/liter-culture and 99% purity. The in vivo antiangiogenic and antitumor activities of the soluble recombinant endostatin are equally as potent as those of the previously published insoluble form. A similar protocol may be used to produce soluble human endostatin. PMID- 11212236 TI - Inhibiting mutations in the transforming growth factor beta type 2 receptor in recurrent human breast cancer. AB - Members of the transforming growth factor beta (TGF-beta) family are potent inhibitors of the growth of many epithelial cell types. Transmembrane signaling by TGF-beta occurs via a complex of the serine/threonine kinases TGF-beta type 1 receptor and TGF-beta type 2 receptor (TGFBR2), and inactivating mutations in the latter have recently been detected in some primary tumors and in several types of tumor-derived cell lines. The most common mutations that have been identified in TGFBR2 are frameshifts in a repetitive polyadenine region in replication error positive colorectal carcinomas that result in a truncated protein and absence of receptor expression at the cell surface. A number of point mutations in the highly conserved serine/threonine kinase domain of TGFBR2 have also been reported, some of which have been correlated with either loss of trans phosphorylation of TGF-beta type 1 receptor or constitutive activation of trans phosphorylation. No TGFBR2 mutations have been reported in human breast tumors, but anomalous expression of TGF-beta in breast carcinomas suggests that TGF-beta signaling may be defective. We have therefore systematically examined unmatched sets of 17 primary and 17 recurrent breast tumor samples for mutations in TGFBR2, restricted to those regions of the gene in which mutations have previously been reported. None of the previously reported mutations was detected, but four novel mutations (V387M, N435S, V447A, and L452M) were found in the kinase domain in recurrent tumors. No mutations were detected in primary tumors. TGF-beta signaling was significantly inhibited by each of the N435S, V447A, and L452M mutations. PMID- 11212237 TI - p53 induction prevents accumulation of aberrant transcripts in cancer cells. AB - Loss of fidelity of the splicing process occurs during tumor progression and can have a deleterious effect on genes like tumor suppressor genes. It was reported recently that the presence of aberrant transcripts of the TSG101 gene in breast cancer cells was associated with the mutation of the p53 tumor suppressor gene. On the basis of this observation, we have analyzed TSG101 transcript patterns in p53-active and p53-inactive cells. Using several isogenic cellular models, we demonstrate that the induction of p53 in cancer cells leads to a significant decrease of aberrant transcripts levels. This indicates a novel implication of p53 in the regulation of the splicing process. PMID- 11212238 TI - Posttranslational truncation and inactivation of human E-cadherin distinguishes prostate cancer from matched normal prostate. AB - An essential event in the progression of adenocarcinoma is the loss of organized epithelial attachment (both to the basement membrane and to adjoining epithelial cells). The E-cadherin cell adhesion molecule has an established function in maintaining normal phenotype and tissue homeostasis, and loss of E-cadherin function has been implicated in tumorigenesis. Aberrations in E-cadherin are associated with prostate cancer progression; however, these aberrations are not simply a result of prodigious allelic loss. We have previously demonstrated a novel posttranslational truncation within the cytosolic domain of native Mr 120,000 E-cadherin to a membrane-bound Mr 97,000 species. We hypothesize that truncation of E-cadherin is an inactivating event that is significantly increased in localized prostate tumors and that it represents a novel molecular event that may distinguish prostate cancer from adjacent normal tissue. E-cadherin was characterized by Western blot analysis in matched normal and cancer tissue from 18 prostate cancer patients. Imaging and densitometry software were used to quantify the truncation of E-cadherin by measuring the ratio of Mr 97,000 E cadherin to Mr 120,000 E-cadherin, which was significantly increased in the tumor aspect of the prostate gland. Herein, we report the first experiment comparing case-matched human normal and cancerous prostate tissue in the context of E cadherin truncation. PMID- 11212239 TI - Oligoclonal T-cell receptor usage of melanocyte differentiation antigen-reactive T cells in stage IV melanoma patients. AB - Ex vivo ELISPOT analysis of peripheral blood lymphocytes obtained from stage IV melanoma patients demonstrated reactivity against peptides derived from MART-1 and gp100. However, the number of reactive T cells was < 1% that of total lymphocytes as detected by flow cytometry using tetrameric MHC/peptide complexes. Despite this low frequency, we were able to directly isolate these populations ex vivo by means of magnetic beads coated with MHC/peptide complexes and to subject these cells to T-cell receptor clonotype mapping. This analysis revealed that the MART-1/A*0201- and gp100/A*0201-reactive T-cell populations are composed of oligoclonal T cells that engage several T-cell receptor beta chain families. Longitudinal studies using this approach may result in a better correlation between T-cell reactivity and the course of neoplastic disease. PMID- 11212240 TI - 15S-Hydroxyeicosatetraenoic acid activates peroxisome proliferator-activated receptor gamma and inhibits proliferation in PC3 prostate carcinoma cells. AB - 15-Lipoxygenase (15-LOX)-2 is expressed in benign prostate secretory cells and benign prostate produces 15S-hydroxyeicosatetraenoic acid (15S-HETE) from exogenous arachidonic acid (AA). In contrast, 15S-LOX-2 and 15S-HETE formation are reduced in prostate carcinoma (Pca). The mechanisms whereby reduced 15-LOX-2 may contribute to Pca development or progression are not known. We investigated the expression of peroxisome proliferator-activated receptor (PPAR) gamma in benign and malignant prostate tissues and the ability of 15S-HETE to activate PPARgamma-dependent transcription and modulate proliferation of the Pca cell line PC3. In contrast to benign prostate and similar to most Pca tissues, 15-LOX-2 mRNA was not detected in PC3 cells, and they did not produce detectable 15-HETE from [14C]AA. By reverse transcription-PCR, PPARgamma mRNA was present in 18 of 18 benign and 9 of 9 tumor specimens. The PPARgamma ligand BRL 49653 and 15S-HETE caused a dose-dependent inhibition of PC3 proliferation in a 14-day soft agar colony-forming assay (IC50 of 3 and 30 microM, respectively). 15S-HETE (10 microM) caused greater inhibition than 10 microM 15R-HETE. At 3 days, BRL 49653 and 15S-HETE caused a slight increase in cells in G0-G1 and a corresponding decrease in cells in S phase. In PC3 cells transiently transfected with a luciferase reporter linked to a PPAR response element, 1 microM BRL 49653 and 10 microM 15S-HETE caused approximately threefold and greater than twofold induction of PPAR-dependent transcription, respectively. By quantitative real-time reverse transcription-PCR and Northern analysis, 3-day treatment with BRL 49653 and 15S HETE caused a reduction of PPARgamma expression but a marked up-regulation of the PPAR response element containing adipocyte type fatty acid binding protein. These results support the hypothesis that 15-LOX-2-derived 15S-HETE may constitute an endogenous ligand for PPARgamma in the prostate and that loss of this pathway by reduced expression of 15-LOX-2 may contribute to increased proliferation and reduced differentiation in prostate carcinoma. PMID- 11212241 TI - Use of camptothecin-resistant mammalian cell lines to evaluate the role of topoisomerase I in the antiproliferative activity of the indolocarbazole, NB-506, and its topoisomerase I binding site. AB - NB-506 is a topoisomerase I (top1) inhibitor in clinical trials. In this study, we used a series of camptothecin (CPT)-resistant cell lines with known top1 alterations. We show that three mutations in different domains of the top1 enzyme that confer CPT resistance also confer cross-resistance to NB-506. The CPT resistant cell lines and corresponding mutations were: human prostate carcinoma cells DU-145/RC1 (mutation R364H), Chinese hamster fibroblasts DC3F/C10 (mutation G503S), and human leukemia CEM/C2 cells (N722S). This result suggests that NB-506 and CPT share a common binding site in the top1-DNA complex. We next used these three cell lines and their parental cells to study the relationship between top1 poisoning by NB-506 and antiproliferative activity. We found that the CPT resistant cells were only 2-10-fold resistant to NB-506, which suggests that NB 506 targets other cellular processes/pathways besides top1. This conclusion was further supported by the limited cross-resistance of top1-deficient murine leukemia P388/CPT45 cells (2-fold). Cross-resistance was also limited for J 109,382, an isomer of NB-506 that does not intercalate into DNA, indicating that the non-top1-mediated antiproliferative activity of NB-506 is not attributable to DNA intercalation. Together, these data indicate that NB-506 and indolocarbazoles are promising agents to overcome CPT resistance. PMID- 11212242 TI - Frequent cytolytic T-cell responses to peptide MAGE-A10(254-262) in melanoma. AB - MAGE genes encode tumor-specific shared antigens that are among the most interesting candidates for cancer vaccines. Despite extensive studies, however, CD8+ T-cell responses to MAGE-derived epitopes have been detected only occasionally in cancer patients, even after vaccination. In contrast with these findings, we report here that HLA-A2 melanoma patients respond frequently to the recently identified peptide MAGE-A10(254-262). Indeed, as assessed by staining with fluorescent HLA-A2/peptide MAGE-A10(254-262) tetramers, CD8+ T cells directed against this peptide were readily detectable in a large proportion of HLA-A2+ melanoma patients. These results provide new insight into the immunogenicity of MAGE antigens and underline the potential usefulness of MAGE A10 peptide-based cancer vaccines. PMID- 11212243 TI - Loss of p53 but not ARF accelerates medulloblastoma in mice heterozygous for patched. AB - Brain malignancies represent the most common solid tumors in children, and they are responsible for significant mortality and morbidity. The molecular basis of the most common malignant pediatric brain tumor, medulloblastoma, is poorly understood. Mutations in several genes including the human homologue of the Drosophila segment polarity gene, patched (PTCH), the adenomatous polyposis coli gene (APC), beta-catenin, and p53 have been reported in subsets of hereditary and sporadic medulloblastoma. Inactivation of one Ptc allele in mice results in a 14% incidence of medulloblastoma. Here, we report a dramatic increase in the incidence (>95%) and accelerated development (prior to 12 weeks of age) of medulloblastoma in mice heterozygous for Ptc that lack p53. The acceleration of tumorigenesis in Ptc+/- mice is specific for loss of p53, because no change in tumor incidence was observed in Ptc+/- mice carrying a mutation in APC (Min+/-) or in Ptc+/- mice deficient in p19ARF. Thus, there is a specific interaction between p53 loss and heterozygosity of Ptc that results in medulloblastoma. This may be a consequence of increased genomic instability associated with loss of p53 function that may enhance the rate of acquisition of secondary mutations. Ptc+/- p53-/- mice provide a useful model for investigation of the molecular bases of medulloblastoma and for evaluation of the efficacy of therapeutic intervention strategies in a spontaneously arising endogenous brain tumor. PMID- 11212244 TI - Antitumor synergy of CV787, a prostate cancer-specific adenovirus, and paclitaxel and docetaxel. AB - CV787, a PSA+ prostate cell-specific adenovirus variant, is currently in Phase I/II clinical trials for the treatment of prostate cancer. We have previously demonstrated that a single administration of CV787 at 1 x 10(11) particle/animal could eliminate established tumors within 6 weeks in nude mouse xenografts (Yu et al., Cancer Res., 59: 4200-4203, 1999). We now demonstrate that CV787-mediated replication-dependent cytotoxicity is synergistic with the chemotherapeutic agents paclitaxel (Taxol) or docetaxel (Taxotere) both in vitro and in vivo. In vitro, cells were pretreated with CV787 24 h before taxane, pretreated with taxane 24 h before CV787, or treated with both agents simultaneously. Cell viability was determined at various time points by 3-[4,5-dimethylthiazole-2-4] 2,5-diphenyl-2H-tetrazolium bromide assay, and virus yield was examined by plaque assay. Addition of taxane to CV787 resulted in a synergistic increase of cytotoxicity toward the human prostate cancer cell line LNCaP, regardless of the timing of administration. There was no reduction in virus replication or specificity of CV787-based cytopathogenicity for prostate cancer cells (approximately 10,000 to 1) with the taxanes. p53 expression was significantly elevated in the cells treated with CV787 and taxane. In vivo, using the PSA+ LNCaP xenograft model of prostate cancer, a single i.v. dose of 1 x 10(8) particles CV787 and docetaxel in combination eliminates large preexistent distant tumors. Toxicity studies do not show a synergistic increase of toxicity of CV787 and taxane. These experiments demonstrate a synergistic antitumor efficacy for CV787 when combined with taxane and demonstrate an in vivo single-dose curative therapeutic index for CV787 of over 1000:1. PMID- 11212245 TI - Intratumoral administration of endostatin plasmid inhibits vascular growth and perfusion in MCa-4 murine mammary carcinomas. AB - Endostatin, a fragment of the COOH-terminal domain of mouse collagen XVIII is a recently demonstrated endogenous inhibitor of tumor angiogenesis and endothelial cell growth. Antiangiogenic therapy with endostatin in animals requires multiple and prolonged administration of the protein. Gene therapy could provide an alternative approach to continuous local delivery of this antiangiogenic factor in vivo. Established MCa-4 murine mammary carcinomas, grown in immunodeficient mice, were treated with intratumoral injection of endostatin plasmid at 7-day intervals. At the time of sacrifice, 14 days after the first injection, endostatin-treated tumor weights were 51% of controls (P < 0.01). Tumor growth inhibition was accompanied by a marked reduction in total vascular density. Specifically, computerized image analysis showed a 18-21% increase in the median distances between tumor cells and both the nearest anatomical (CD31-stained) vessel [48.1 +/- 3.8 versus 38.3 +/- 1.6 microm (P < 0.05)] and the nearest tumor specific (CD105-stained) vessel [48.5 +/- 1.5 versus 39.8 +/- 1.5 microm (P < 0.01)]. An increased apoptotic index of tumor cells in endostatin-treated tumors [3.2 +/- 0.5% versus 1.9 +/- 0.3% (P < 0.05)] was observed in conjunction with a significant decrease in tumor perfused vessels (DiOC7 staining), and an increase in tumor cell hypoxia (EF5 staining). Hypoxia resulting from endostatin therapy most likely caused a compensatory increase of in situ vascular endothelial growth factor (VEGF) and VEGF receptor mRNA expression. Increased immunoreactivity of endostatin staining in endostatin-treated tumors was also associated with an increased thrombospondin-1 staining [1.12 +/- 0.16 versus 2.44 +/- 0.35]. Our data suggest that intratumoral delivery of the endostatin gene efficiently suppresses murine mammary carcinoma growth and support the potential utility of the endostatin gene for cancer therapy. PMID- 11212246 TI - Direct evidence of the importance of stromal urokinase plasminogen activator (uPA) in the growth of an experimental human breast cancer using a combined uPA gene-disrupted and immunodeficient xenograft model. AB - Several studies have indicated an interaction between tumor cells and infiltrating stromal cells regarding the urokinase plasminogen activation (uPA) system. By developing combined uPA gene-disrupted and immunodeficient mice, we have studied the role of stromal uPA for the growth of the MDA-MB-435 BAG human tumor xenograft. Subcutaneous tumor growth and lung metastasis were compared between wild-type immunodeficient mice and mice with the combined deficiencies. Tumor growth was evaluated by volume measurements and plasma beta-galactosidase activity and metastasis was evaluated by counting lung surface metastases. Although no differences appeared in primary tumor take between the two groups of mice, a significant difference was observed in primary tumor growth, with tumors in uPA-/- mice growing significantly more slowly. In addition, a nonsignificant trend toward fewer lung metastases in uPA-/- mice was observed. The present data points to a critical role of stromal-derived uPA in the primary tumor growth of MDA-MB-435 BAG xenografts, whereas only a trend toward fewer lung metastases in uPA gene-disrupted mice was found. PMID- 11212247 TI - Deregulated expression of c-mos in non-small cell lung carcinomas: relationship with p53 status, genomic instability, and tumor kinetics. AB - Little is known about the status of the mitogen-activating protein kinase pathways in lung cancer. One of the key molecules taking part in these pathways is the product of the c-mos proto-oncogene, which plays an important role in oocyte maturation. In vitro investigations in somatic cells have shown that c-mos expression has opposing effects on the cell cycle, which suggests that this proto oncogene may represent an important determinant of aberrant cell function (genomic instability and altered kinetics). A recent study suggests that these effects may be p53 dependent. In view of the apparent link between c-mos and p53, we investigated in a series of 56 non-small cell lung carcinomas: a) the status of c-mos; b) its relationship to genomic instability (aneuploidy) and two kinetic parameters of the tumors, proliferation and apoptotic indexes (AI); and c) its association with p53 alterations and their concomitant relationship with the above parameters. We found c-mos overexpression in 27% of the tumors. Expression was higher in stages II/III (34%) than in stage I (17%; P = 0.018). Complete concordance was observed between c-mos overexpression and elevated c-mos mRNA levels. Because c-mos gene amplification was not detected, its deregulated expression may be attributable to increased transcription. Of the c-mos positive [c-mos(P)] cases, 77% were associated with aneuploidy. Sequencing showed two silent mutations and one missense (R-->L) at codon 22, located in a region critical for c-mos stability. In contrast to the findings of some in vitro studies, c-mos(P) tumors had a lower mean AI score than the c-mos negative [c mos(N)] tumors had, implying that induction of apoptosis may have been defective. Indeed, 86% of the tumors overexpressing c-mos showed p53 alterations. The carcinomas with concomitant alterations of c-mos and p53 [c-mos(P)/p53 positive] had significantly lower AI values (P < 0.001) and were more frequently associated with aneuploidy (P = 0.015) than the c-mos(N)/p53 negative tumors but not the c mos(N)/p53 positive tumors, which suggests that p53 status is the main determinant of ploidy status and apoptosis in our series. This finding also strengthens the concept that wild-type p53 plays a "safeguard" role in preventing oncogene-mediated activation. PMID- 11212248 TI - Transforming growth factor-beta1 induces desmoplasia in an experimental model of human pancreatic carcinoma. AB - Proliferation of fibrotic tissue (desmoplasia) is one of the hallmarks of several epithelial tumors including pancreatic adenocarcinoma. This tissue reaction may be deleterious or advantageous to the host or tumor. In a systematic analysis, we identified two growth factors expressed by human pancreatic carcinoma cells that are positively correlated with the ability to induce fibroblast proliferation both in vitro and in vivo, i.e., transforming growth factor (TGF)-beta1 and fibroblast growth factor-2. Here we demonstrate that the overexpression of TGF beta1 induced up-regulation of matrix proteins and growth factors in the TGFbeta1 transfected pancreatic tumor cells. Furthermore, transfection of PANC-1 cells induces the same change in fibroblasts in either cocultivation experiments or when they are grown in conditioned medium from TGF-beta1-transfected PANC-1 cells. TGF-beta1-transfected pancreatic tumor cells induced a rich stroma after orthotopical transplantation in the nude mouse pancreas. The transfer of a single growth factor, TGF-beta1, conveys the ability to induce a fibroblast response similar to that seen in desmoplasia in human pancreatic adenocarcinoma. This effect cannot only be attributed to direct effects of TGF-beta1 but also results from the up-regulation of several other factors including collagen type I, connective tissue growth factor, and platelet-derived growth factor. PMID- 11212249 TI - Increased retinoic acid responsiveness in lung carcinoma cells that are nonresponsive despite the presence of endogenous retinoic acid receptor (RAR) beta by expression of exogenous retinoid receptors retinoid X receptor alpha, RAR alpha, and RAR gamma. AB - Nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs) are thought to mediate most of the effects of retinoids on cell growth and differentiation. Despite expressing abundant levels of RAR beta mRNA, lung adenocarcinoma H1792 cells are resistant to the growth-inhibitory effects of all trans-retinoic acid, suggesting that they have a defect in retinoid signaling. To determine whether transfection of exogenous receptors can restore retinoid responsiveness, we transiently transfected into H1792 cells coexpression vectors containing cDNAs of cell surface antigen CD7 and either RAR alpha, RAR beta, RAR gamma, or RXR alpha. The cells were then treated with retinoids and incubated with 5'-bromo-2'-deoxyuridine. Cells that express exogenous receptor were identified using antibodies against CD7, and cells that synthesized DNA were identified with anti-5'-bromo-2'-deoxyuridine antibodies using secondary antibodies with red and green fluorescence, respectively. RXR alpha and RAR alpha enhanced growth inhibition by all-trans-retinoic acid or 9-cis-retinoic acid, whereas RAR gamma was less effective, and RAR beta was ineffective. The effects of the transfected receptors were associated with antagonism of activator protein 1 (AP-1) activity. Studies with RXR alpha deletion and point mutants indicated that growth suppression is: (a) dependent on intact DNA-binding and ligand binding regions but not on the NH2-terminal region, which contains a ligand independent transactivation function; (b) dependent on RXR homodimer formation and transactivation of RXR response element; and (c) associated with AP-1 antagonism. These results demonstrate that transfected receptors can restore responsiveness to retinoids by antagonizing AP-1 in H1792 cells. PMID- 11212250 TI - Targeted inactivation of the p21(WAF1/cip1) gene enhances Apc-initiated tumor formation and the tumor-promoting activity of a Western-style high-risk diet by altering cell maturation in the intestinal mucosal. AB - Elimination of both alleles of the gene that encodes the cyclin kinase inhibitor p21(WAF1/cip1) increases the frequency and size of intestinal tumors in Apc1638+/ mice that inherit a mutant allele of the Apc gene, and intermediate effects are seen if a single p21 allele is inactivated. The increased tumor formation is associated with altered cell maturation in the intestinal mucosa of the p21 deficient mice--increased cell proliferation, and decreased apoptosis, and goblet cell differentiation--that is also a function of p21 gene dosage. Moreover, a Western-style diet that mimics principal risk factors for colon cancer (high fat and phosphate, low calcium and vitamin D) accelerates tumor formation in Apc1638+/- mice, and the loss of a single or both p21 alleles is additive with the tumor-promoting effects of this diet, resulting in more and larger tumors, and a highly significant decrease in survival time. Thus, p21 normally suppresses Apc-initiated tumor formation and is haplo-insufficient in this regard. This is consistent with recent reports that Apc initiates tumor formation by up regulating c-myc expression through altered beta-catenin-Tcf signaling and that c myc then up-regulates cdk4, whose activity is inhibited by p21. Decreased expression of p21 is also a marker of poor prognosis in patients, and the data presented suggest that dietary alterations in patients undergoing treatment for colon cancer might be highly effective in improving outcome. PMID- 11212251 TI - The Sp family of transcription factors in the regulation of the human and mouse MUC2 gene promoters. AB - Modulation of mucin gene expression is an important component both in the early steps of colon cancer development and in later tumor progression. Previous work from our laboratory and others has suggested that the Sp family of transcription factors may play an important role in the regulation of the human MUC2 gene. To determine whether this was an essential element, we extended our work to the cloning and analysis of 3.5 kb of the 5'-flanking region of the mouse Muc2 (mMuc2) gene. Comparative analysis between the mouse and human MUC2 promoter regions has identified a strong sequence homology between the mouse and human genes, including the presence of GC-rich boxes, the location and composition of which are maintained in the mouse and human genes. We show that these GC boxes are binding sites for Sp-family transcription factors and are functionally important since mithramycin, an inhibitor of Sp1/Sp3 binding, blocks MUC2 gene expression in HT29 cells. Furthermore, by a combination of gel shift analysis and site-directed mutagenesis, we have identified the relative contribution of individual GC boxes, and of the factors they bind, to the regulation of the mouse Muc2 promoter, which appears to be different in the mouse and human genes. Finally, we demonstrate by overexpressing Sp1 and Sp3 that the functional difference between the proximal promoter region of the MUC2 gene in the two species is not attributable to differential ability of this region to bind members of the Sp family of transcription factors, but rather to the different anatomy of the individual GC boxes in the mouse and human proximal promoters. PMID- 11212252 TI - Matrix metalloproteinase-7-mediated cleavage of Fas ligand protects tumor cells from chemotherapeutic drug cytotoxicity. AB - Recent evidence suggests that one mechanism whereby cytotoxic drugs, such as doxorubicin, kill tumors is the induction or up-regulation of Fas ligand (FasL) expression on the tumor cell surface. The ensuing engagement of Fas by FasL on adjacent cells leads to apoptosis. However, despite cytotoxic drug-induced FasL expression, Fas-sensitive tumors frequently resist chemotherapy, suggesting that they may possess a mechanism that prevents or inactivates Fas-FasL interactions. In the present work, we addressed the involvement of the FasL/Fas signaling pathway in doxorubicin-induced apoptosis and the ability of matrix metalloproteinases (MMPs) to proteolytically cleave FasL in tumor cells. Doxorubicin-induced apoptosis was inhibited by expression of soluble Fas or incubation of the tumor cells with MMP-7 but not with MMP-2 or MMP-9. Resistance to doxorubicin was also induced by expression in the tumor cells of constitutively active MMP-7 but not of a catalytically inactive mutant. Conversely, inhibition of MMP-7 expression in tumor cells by transfection of MMP 7 cDNA in antisense orientation resulted in sensitization to doxorubicin. MMP-7 efficiently cleaved recombinant FasL in vitro and reduced cell surface FasL expression. Our observations provide evidence that one mechanism whereby MMP-7 may promote tumor survival and resistance to doxorubicin is by cleaving FasL and reducing its effectiveness in triggering Fas-mediated apoptosis. PMID- 11212253 TI - Overexpression of the G-protein inwardly rectifying potassium channel 1 (GIRK1) in primary breast carcinomas correlates with axillary lymph node metastasis. AB - The acquisition of genetic alterations in tumor cells is a hallmark of cancer progression. Genetic alterations, including chromosomal sequence alterations and abnormal gene expression, increase the malignant potential of tumors by affecting pathways that regulate cell growth, cell death, tumor angiogenesis, and invasion/metastasis. We used an expression profiling technique, representational difference analysis, to identify genes the expressions of which are aberrantly increased in invasive breast carcinomas as compared with adjacent normal breast tissue from the same individual. Among the genes we identified was GIRK1, which encodes a 501 amino acid, G-protein inwardly rectifying potassium channel protein. We then measured GIRK1 mRNA expression in benign breast tissues, primary invasive breast carcinomas, and metastatic breast carcinomas from axillary lymph nodes using quantitative TaqMan reverse transcription-PCR and correlated the results with clinical parameters. We found that GIRK1 overexpression correlated with lymph node metastasis (P < 0.0029), and overexpression was greatest in tumors with more than one positive lymph node. These results indicate that GIRK1 may be useful as a biomarker for lymph node metastasis and possibly a pharmaceutical target. PMID- 11212254 TI - AKT activation up-regulates insulin-like growth factor I receptor expression and promotes invasiveness of human pancreatic cancer cells. AB - Insulin-like growth factor I receptor (IGF-IR) is frequently overexpressed in several types of human malignancy and is associated with invasion and metastasis of tumor cells. Recently, IGF-IR expression was reported to be up-regulated in the human pancreatic cancer cell line PANC-1 when cells were stably transfected with active Src. The downstream targets of Src that lead to the up-regulation of IGF-IR expression were previously unknown. We demonstrate here that AKT regulates IGF-IR expression in PANC-1 and AsPC-1 cells. Cells transfected with active Src exhibited significantly more IGF-IR protein compared with vector-transfected cells. Overexpression of wild-type or constitutively active AKT (i.e., AKT1 or AKT2) also resulted in elevated IGF-IR expression. IGF-IR protein levels were higher in cells transfected with constitutively active AKT than in cells transfected with active Src. In vitro kinase assays showed that AKT kinases are activated by active Src and inhibited by dominant negative Src or the tumor suppressor PTEN. Furthermore, AKT-induced IGF-IR expression was down-regulated by dominant-negative Src or PTEN. In addition, cells transfected with activated AKT in the presence of IGF-I were shown to have enhanced invasiveness compared with control cells. These data provide evidence for a link between AKT signaling and the regulation of IGF-IR expression and demonstrate that active AKT promotes the invasiveness of pancreatic cancer cells through the up-regulation of IGF-IR expression. PMID- 11212255 TI - Bcl-2 delays and alters hepatic carcinogenesis induced by transforming growth factor alpha. AB - Transgenic mice that overexpress transforming growth factor (TGF)-alpha develop liver tumors between 12 and 15 months of age. Tumor development is preceded by an overall increase in the rates of hepatocyte proliferation and cell death. To examine the role of apoptosis in the development of TGF-alpha-induced liver tumors, we generated TGF-alpha/Bcl-2 double transgenic mice by crossing TGF-alpha transgenic mice with Bcl-2 transgenic mice expressing a zinc-inducible Bcl-2 transgene. Overexpression of the Bcl-2 transgene protected hepatocytes from Fas mediated apoptosis. We anticipated that hepatocytes in TGF-alpha/Bcl-2 double transgenic mice would be stimulated to proliferate but would fail to undergo apoptosis, leading to increased liver weights and accelerated tumorigenesis. At 4 weeks of age, both TGF-alpha single transgenic and TGF-alpha/Bcl-2 double transgenic mice had elevated hepatocyte proliferation and increased liver:body weight ratios. However, by 8 months, the liver:body weight ratios had normalized in both TGF-alpha single transgenic and TGF-alpha/Bcl-2 double transgenic mice. Furthermore, Bcl-2 functioned as a tumor suppressor, significantly decreasing the frequency and delaying the development of TGF-alpha-induced liver tumors, despite having comparable levels of TGF-alpha transgene expression in both single and double transgenic mice. Between 11 and 12 months of age, >80% of the TGF-alpha single transgenic mice had developed tumors, whereas only 54% of the double transgenic mice had developed tumors after 13 months of age. The tumors that eventually developed in the TGF-alpha/Bcl-2 double transgenic mice were histologically distinct and smaller in size and had lower hepatocyte mitotic activity than tumors from TGF-alpha single transgenic mice. Furthermore, delaying Bcl-2 expression until 8.5 months of age was sufficient to inhibit TGF-alpha induced tumorigenesis. These results indicate that Bcl-2 inhibits tumor progression in the liver, possibly by interfering with hepatocyte proliferation. PMID- 11212256 TI - Raf-induced transformation requires an interleukin 1 autocrine loop. AB - The c-Raf-1 serine/threonine protein kinase plays a critical role in the proliferation of most cell types that have been examined. As such, the Raf proto oncogene is thought to play a central role in the development of human tumors. Although the c-raf-1 gene itself rarely appears to be mutated in human tumors, the kinase activity of Raf is frequently found to be more active in tumor cells, likely through constitutive activation of upstream activators of Raf. The downstream events triggered by Raf that are involved in transformation have been studied less extensively. We show in this study that Raf-induced transformation of NIH 3T3 cells requires the activation of the ubiquitously expressed transcription factor, nuclear factor-kappaB, by Raf. Furthermore, through the use of CrmA, interleukin 1 (IL-1) receptor antagonist, and a dominant-negative form of TRAF6, we demonstrate a requirement for IL-1 production and signaling from the IL-1 receptor as necessary components of Raf-induced transformation. These results indicate that IL-1 may be used as an autocrine growth factor by a number of tumors in which activation of Raf plays an important role in transformation and suggest that blockade of IL-1 signaling may be an approach to limiting the growth of certain tumors. PMID- 11212257 TI - p53 codon 72 polymorphism and various human papillomavirus 16 E6 genotypes are risk factors for cervical cancer development. AB - Risk factors other than human papillomavirus (HPV) infection per se for cervical cancer development have been investigated recently. It was suggested that HPV 16 E6 variants and the p53 codon 72 arginine polymorphism could be progression markers. Indeed, it has been demonstrated that specific E6 variants and p53 arginine were both enriched in cancer. However, especially with regard to the latter, divergent results have been reported. Our aim was thus to investigate whether p53 arginine is important for cervical carcinogenesis by scaling up samples of the two European cohorts, the initial results of which were reported previously. In addition, we have assessed the occurrence of p53 codon 72 arginine, in combination with specific HPV 16 E6 genotypes. We found p53 arginine to be increased in cancer of both cohorts, consistent with our previous concept. Although specific E6 genotypes increased gradually with the severity of the lesion, p53 arginine was enriched in cancer only. Moreover, the frequency of the arginine allele was similar in groups with different E6 genotypes. It is concluded that p53 arginine is a risk factor for cervical cancer but probably acts independently of E6 variants. PMID- 11212258 TI - Tobacco smoke-induced DNA damage and an early age of smoking initiation induce chromosome loss at 3p21 in lung cancer. AB - The short arm of chromosome 3 is thought to harbor a novel oncogenic locus that is important in the genesis of lung cancer. The region at 3p21 is believed to contain a distinct locus that is sensitive to loss from the action of tobacco smoke carcinogens and has been reported to be specifically targeted for deletion in lung cancer. To investigate whether 3p21 alteration in lung cancer is associated with carcinogen exposure, PCR-based analysis was performed to detect loss of heterozygosity (LOH) on chromosome 3 at 3p21 in non-small cell lung carcinoma (NSCLC). We also measured instability at the BAT-26 locus, because the mismatch DNA repair gene, hMLH1, is found at 3p21. LOH at 3p21 was analyzed for association with the clinical features of NSCLC, p53 mutation status, polynuclear aromatic hydrocarbon-DNA adduct levels (measured using 32P-postlabeling) and carcinogen exposure information including cigarette smoking and asbestos exposure. Of 219 lung cancers, 150 cases (68.5%) were informative at the D3S1478 locus, and 44.2% of squamous cell carcinoma cases and 30.2% of adenocarcinoma cases showed 3p21 LOH. None of the cancers showed BAT-26 instability. The prevalence of 3p21 LOH was higher in both current and former smokers compared with never smokers and was higher in p53 mutated cases. Among squamous cell carcinoma cases, there was a strong association of increased 3p21 LOH with increasing polynuclear aromatic hydrocarbon-DNA adducts levels (P = 0.03), as well as an increased prevalence LOH with earlier age of smoking initiation (P = 0.02). Our results confirm that 3p21 LOH is strongly associated with measures of biologically effective dose of exposure to tobacco carcinogens. Our results also suggest that alterations of hMLH1 are not related to any of the reported associations, because there was no evidence of microsatellite instability. Finally, LOH in 3p21 may be an early molecular event in NSCLC, because it is significantly associated with a tendency to start smoking at a young age. PMID- 11212260 TI - Hypergastrinemia promotes adenoma progression in the APC(Min-/+) mouse model of familial adenomatous polyposis. AB - Serum hypergastrinemia promotes the growth of colorectal adenocarcinoma. Some colorectal adenomas express cholecystokinin B/gastrin receptor mRNA, and thus hypergastrinemia may increase progression through the adenoma-carcinoma sequence. This was investigated in the multiple intestinal neoplasia APC(Min-/+) mouse. Serum gastrin levels in APC(Min-/+) mice were elevated 5-6-fold by oral administration of omeprazole (75 mg/kg). Terminal tumor burden was monitored by onset of anemia. A labeling index was generated by immunohistochemical detection of bromodeoxyuridine incorporation. Serum gastrin was neutralized by antigastrin antibodies raised in situ by use of a gastrin immunogen, Gastrimmune. Hypergastrinemia resulted in reduced survival of the APC(Min-/+) mice from a median survival of 13 weeks in the controls to 10 weeks following omeprazole treatment (P < 0.00001, log-rank test). The labeling indices of adenomas from the small and large intestines of omeprazole-treated mice were increased 35 and 29%, respectively (P < 0.05 and P < 0.025, respectively). Gastrimmune immunization reversed both the survival effect and the increased proliferation resulting from serum hypergastrinemia. Hypergastrinemia may promote the progression of existing premalignant colonic lesions by increasing proliferation. Clinical investigations should determine whether this occurs in the human scenario, considering the widespread use of proton pump inhibitors. PMID- 11212259 TI - Human papillomavirus type 16 E6 inactivation of p53 in normal human mammary epithelial cells promotes tamoxifen-mediated apoptosis. AB - Aberrant p53 expression is frequently observed in mammary epithelial cells obtained from women at high risk for developing breast cancer and is a predictor for the subsequent development of malignancy. Tamoxifen has recently been shown to reduce the incidence of noninvasive breast cancer in high-risk women, but the molecular mechanism of tamoxifen chemoprevention in mammary epithelial tissue that does not overexpress the estrogen receptor is poorly understood. We suppressed p53 expression by retroviral-mediated expression of human papillomavirus type-16 E6 protein (HPV-16 E6) in human mammary epithelial cells (HMECs) to develop an in vitro model of tamoxifen chemoprevention in the context of p53 loss. Early passage p53(-) HMEC-E6-transduced cells treated with 1.0 microM tamoxifen rapidly underwent apoptosis. In contrast, early passage p53(+) HMEC-LXSN vector controls treated with 1.0 microM tamoxifen underwent G1-G0-phase arrest but did not undergo apoptosis. p53(-) HMEC-E6 cells rapidly acquired resistance to tamoxifen-mediated apoptosis after 10 passages in culture (in the absence of tamoxifen). Both p53(+) and p53(-) HMECs exhibited a low level of estrogen receptor staining and minimal estrogen binding, characteristic of proliferating normal luminal mammary epithelial cells. Tamoxifen-mediated apoptosis in p53(-) HMEC-E6 cells was not blocked by inhibitors of transcription and protein synthesis. These data suggest that the acute loss of p53 function in HMECs by expression of HPV-16 E6 results in marked sensitivity to tamoxifen mediated apoptosis but that resistance to apoptosis rapidly develops within 10 passages in vitro. Observations in our model system predict a critical role for the early institution of tamoxifen chemoprevention. PMID- 11212261 TI - Expression of estrogen receptor (ER) subtypes and ERbeta isoforms in colon cancer. AB - Colon cancer incidence and mortality rates are lower in females compared with males, and numerous epidemiological studies suggest that estrogen replacement therapy (ERT) reduces cancer risk in postmenopausal women. Two estrogen receptor (ER) subtypes, ERalpha and ERbeta, mediate genomic effects in target cells. The aim of this study was to determine the relative mRNA expression levels for ER subtypes and ERbeta isoforms in colon tumors, normal colonic mucosa, and colon cancer cell lines. ERalpha and ERbeta isoform mRNA levels were investigated in paired samples of colon tumors and normal mucosa from 26 patients using comparative reverse transcription-PCR and then Southern analyses. Constitutive steroid hormone receptor mRNA levels were determined for five colon adenocarcinoma cell lines using reverse transcription-PCR, and ERbeta levels were further studied in Caco-2 cells using Northern and Western analyses. ERbeta mRNA steady-state levels (relative to glyceraldehyde-3-phosphate dehydrogenase mRNA) were significantly decreased in colon tumors compared with normal mucosa in female patients. ERbeta1 and ERbeta2 isoform mRNA levels were significantly decreased in tumors from female patients, and ERbeta1 mRNA levels were also significantly lower in tumors from female patients compared with tumors from males. ERalpha mRNA levels were much lower than ERbeta levels and were similar between normal mucosa and tumor samples in both genders. ERbeta mRNA was detected in Caco-2, T84, and SW1116 cell lines and all lines were essentially negative for ERalpha mRNA. Caco-2 cells coexpressed ERbeta1, ERbeta2, and ERbeta5 mRNA, though a single protein transcript was observed. ERbeta protein was detected in normal colonic superficial epithelium, vascular smooth muscle and endothelium, and enteric neurons by immunohistochemistry. These data show that ERbeta is the predominant ER subtype in the human colon and that decreased levels of ERbeta1 and ERbeta2 mRNA are associated with colonic tumorigenesis in females. This information suggests that activation of ERbeta-mediated processes in the superficial colonic epithelium may have a role in the preventive effects observed for female gender and ERT usage. PMID- 11212262 TI - Intranodal immunization with tumor lysate-pulsed dendritic cells enhances protective antitumor immunity. AB - We developed a technique for direct inguinal lymph node injection in mice to compare various routes of immunization with tumor lysate-pulsed dendritic cell (DC) vaccines. Syngeneic, bone marrow-derived, tumor lysate-pulsed DCs administered intranodally generated more potent protective antitumor immunity than s.c. or i.v. DC immunizations. Intranodal immunization with ovalbumin peptide-pulsed DCs induced significantly greater antigen-specific T-lymphocyte expansion in the spleen than either s.c. or i.v. immunization. Furthermore, a significantly more potent, antigen-specific TH1-type response to the ovalbumin peptide was induced by intranodal, compared with s.c. or i.v., immunization. Intranodal immunization, designed to enhance DC-T cell interaction in a lymphoid environment, optimizes induction of T lymphocyte-mediated protective antitumor immunity. These results support the use of intranodal immunization as a feasible and effective route of DC vaccine administration. PMID- 11212263 TI - Cyclin E is the only cyclin-dependent kinase 2-associated cyclin that predicts metastasis and survival in early stage non-small cell lung cancer. AB - Progression through G1-S transition and S phase of the cell cycle is mediated by cyclin-dependent kinase 2 (cdk2), which interacts with several cyclins. Two of these, cyclin E and cyclin A2 (also known as cyclin A), are overexpressed in many cancers. Cyclin E2 and cyclin A1 are recently discovered cdk2-interacting cyclins that are found in malignant tumor cell lines and in acute myeloid leukemia, respectively. Expression and prognostic role of these cyclins in solid tumors is unknown. Here, we have analyzed expression and prognostic relevance of the cdk2 associated cyclins in non-small cell lung cancer (NSCLC). Fresh-frozen biopsies (n = 70) from completely resected tumors with stage I to IIIA NSCLC were studied. Gene expression was analyzed by quantitative real-time reverse transcription-PCR. Expression levels of cyclin E (P = 0.04) and cyclin A2 (P = 0.004) were significantly higher in the tumor samples than in normal controls. Cyclin A1, cyclin A2, and cyclin E2 expression levels did not have prognostic relevance for survival. The mean survival time associated with low and high levels of cyclin E was 69.4 and 47.2 months, respectively, which was statistically significant (P = 0.03). Differences in survival were particularly pronounced in stages I and II. Cyclin E was also closely associated with the development of distant metastasis (P = 0.01). Finally, we confirmed by immunohistochemistry analyses that cyclin E mRNA expression was closely associated with cyclin E protein expression. In conclusion, cyclin E is a strong independent prognostic indicator in patients with early-stage NSCLC, whereas cyclin E2, cyclin A1, and cyclin A2 do not have a prognostic role in NSCLC. PMID- 11212264 TI - Glycophosphatidylinositol-anchored protein deficiency as a marker of mutator phenotypes in cancer. AB - Phosphatidylinositol glycan-A (PIGA) is a gene that encodes an element required for the first step in glycosylphosphatidylinositol (GPI) anchor assembly. Because PIGA is X-located, a single mutation is sufficient to abolish cell surface GPI anchored protein expression. In this study, we investigated whether mutation of the PIGA gene could be exploited to identify mutator (Mut) phenotypes in cancer. We examined eight Mut colon cancer lines and four non-Mut colon cancers as controls. In every case, flow cytometric analyses of cells sorted for low fluorescence after staining for GPI-linked CD59 and CD55 revealed negative peaks in the Mut lines but not in the controls. Single cell cloning of purged and sorted GPI-anchor- HCT116 cells and sequencing of the PIGA gene in each clone uniformly showed mutations. Pretreatment of the Mut lines with anti-CD55 or anti CD59 antibodies and complement or with the GPI-anchor-reactive bacterial toxin aerolysin enriched for the GPI-anchor- populations. Expansion of purged GPI anchor+ cells in the Mut lines and analyses using aerolysin in conjunction with flow cytometry yielded PIGA gene mutation frequencies of 10(-5) to 10(-4), values similar to the mutation frequencies of the hprt gene. This novel approach allows for the detection of as yet undescribed repair or replication defects and in addition to its considerably greater ease of use than existing techniques and in principle would not require the production of cell lines. PMID- 11212266 TI - Creation and characterization of 5-fluorodeoxyuridine-resistant Arg50 loop mutants of human thymidylate synthase. AB - Thymidylate synthase catalyzes the reductive methylation of dUMP to dTMP and is essential for the synthesis of DNA. Fluoropyrimidines, such as 5-fluorouracil (5 FU), are used extensively in cancer therapy. In the cell, 5-FU is metabolized to 5-fluoro-2'-deoxyuridine 5'-monophosphate, a tight binding covalent inhibitor of thymidylate synthase. Recent studies have identified 5-fluoro-2'-deoxyuridine (5 FdUR) and antifolate-resistant mutants of human thymidylate synthase (TS) that contain single residue substitutions within the highly conserved Arg50-loop, which binds the pyrimidine substrate (Y. Tong et al., J. Biol. Chem. 273: 11611 11618, 1998). We have used random sequence mutagenesis to gain structure-function information about the TS and to create novel drug-resistant mutants for gene therapy. A library of 1.5 million mutants of the Arg50-loop and the nearby residue Tyr 33 was selected to identify mutants of the human enzyme with the ability to complement a thymidylate synthase-deficient Escherichia coli strain and form colonies in the presence of 5-FdUR. E. coli-harboring plasmids that were encoding TS with single, double, and triple amino acid substitutions were identified that survive at dosages of 5-FdUR clearly lethal to E. coli harboring either wild-type thymidylate synthase or constructs encoding previously characterized drug resistant mutants. Four 5-FdUR-resistant mutants were purified to apparent homogeneity. Kinetic studies indicate that these enzymes are highly efficient. Inhibition constants (Ki) for the double mutant K47Q;D48E and the triple mutant D48E;T51S;G52C in the presence of 5-fluoro-2'-deoxyuridine 5' monophosphate were determined to be 75 to 100 times higher, respectively, than that of the wild-type enzyme. These mutant TSs, or others similarly created and selected, could be used to protect bone marrow cells from the cytotoxic side effects of 5-FU chemotherapy. PMID- 11212265 TI - Bax accelerates tumorigenesis in p53-deficient mice. AB - Bax is a Bcl-2 family member that promotes apoptosis and counters the protective effect of Bcl-2. Bax is a downstream effector of p53-induced apoptosis and is transcriptionally regulated by p53. Moreover, the introduction of Bax deficiency accelerates the onset of tumors in transgenic mice expressing truncated large T antigen. These results implicate Bax as a tumor suppressor. Consequently, we asked whether the levels of Bax expression would influence tumor development by comparing Bax-deficient and Bax transgenic mice in the presence or absence of p53. We found that Bax-deficient mice did not display an increased incidence of spontaneous cancers when followed for > 1.5 years. In addition, Bax-deficiency did not further accelerate oncogenesis in mice also deficient in p53. We generated Lck(pr)-Bax transgenic mice to examine the effects of overexpressed BAX on T-cell development and tumorigenesis. Lck(pr)-Bax mice show increased apoptosis consistent with the pro-apoptotic function of Bax. The introduction of p53-deficiency did not interfere with BAX-induced apoptosis; this is consistent with BAX operating downstream or independent of p53. However, we found that Lck(pr)-Bax/p53-deficient mice have an increased incidence of T-cell lymphomas when compared with p53-deficient mice. The Lck(pr)-Bax transgenic mice have an increased percentage of cells in cycle. These findings extend previous work suggesting that Bcl-2 family proteins regulate proliferation as well as cell death. We conclude that BAX-induced proliferation is synergistic with a defect in apoptosis contributed by p53-deficiency. Thus, the dual roles of BAX can either accelerate or inhibit tumorigenesis depending on the genetic context. PMID- 11212268 TI - Homozygous deletion of CDKN2A (p16INK4a/p14ARF) but not within 1p36 or at other tumor suppressor loci in neuroblastoma. AB - Loss of heterozygosity of several specific genomic regions is frequently observed in neuroblastoma tumors and cell lines, but homozygous deletion (HD) is rare, and no neuroblastoma tumor suppressor gene (TSG) has yet been identified. We performed a systematic search for HD, indicative of a disrupted TSG, in a panel of 46 neuroblastoma cell lines. An initial search focused on a well-characterized consensus region of hemizygous deletion at 1p36.3, which occurs in 35% of primary neuroblastomas. Each cell line was screened with 162 1p36 markers, for a resolution of 13 kb within the consensus 1p36.3 deletion region and 350 kb throughout the remainder of 1p36. No HDs were detected. This approach was expanded to survey 21 known TSGs, specifically targeting intragenic regions frequently inactivated in other malignancies. HD was detected only at the CDKN2A (p16INK4a/p14ARF) gene at 9p21 and was observed in 4 of 46 cell lines. The observed region of HD included all exons of both CDKN2A and the closely linked CDKN2B (p15INK4b) gene for cell lines LA-N-6 and CHLA-174, all exons of CDKN2A but none of CDKN2B for CHLA-179, and only 104 bp within CDKN2A exon 2 for CHLA 101. All four deletions are predicted to inactivate the coding regions of both p16INK4a and p14ARF. HD was observed in corresponding primary tumor samples for CHLA-101 and CHLA-174 but was not present in constitutional samples. These results suggest that for neuroblastoma, large HDs do not occur within 1p36, most known TSGs are not homozygously deleted, and biallelic inactivation of CDKN2A may contribute to tumorigenicity in a subset of cases. PMID- 11212267 TI - Nuclear factor-kappaB-dependent expression of metastasis suppressor KAI1/CD82 gene in lung cancer cell lines expressing mutant p53. AB - KAI1/CD82 has been shown to be a metastasis suppressor for several human cancers, and a recent study revealed that wild-type tumor suppressor p53 can directly activate KAI1/CD82 gene expression. However, the response of KAI1/CD82 expression in cancer cells to exogenous stimulants has not been investigated. The present study examined whether tumor necrosis factor (TNF), which mediates many of the cellular responses associated with inflammatory reactions or cancer progression, can affect the KAI1/CD82 expression in lung cancer cells and, if so, whether nuclear factor (NF)-kappaB, a key molecule in TNF-mediated gene expression, is involved in the mechanism of KAI1/CD82 induction. Our results demonstrated that expression of KAI1/CD82 in PC-14 cells expressing mutant p53 could be augmented by TNF-alpha, and that transfer of the gene for a specific inhibitor of NF kappaB, IkappaB alphaSR (mutant IkappaB alpha; NF-kappaB super-repressor), into PC-14 cells could inhibit this augmentation. The amount of NF-kappaB in the nucleus of PC-14/IkappaB alphaSR cells correlated well with KAI1/CD82 mRNA and protein expression. In addition, IkappaB alphaSR gene transfer inhibited the spontaneous expression of KAI1/CD82 protein in KAI1/CD82-high-expressing RERF-LC OK cells, which contain a mutant-type p53. These observations indicate that NF kappaB activation may play a role in the regulation of KAI1/CD82 expression in lung cancer cells independently of wild-type p53, and suggest that KAI1/CD82 expression may be regulated by interaction with the host microenvironment. PMID- 11212269 TI - Glucagon-like peptide (GLP)-2 reduces chemotherapy-associated mortality and enhances cell survival in cells expressing a transfected GLP-2 receptor. AB - Chemotherapeutic agents produce cytotoxicity via induction of apoptosis and cell cycle arrest. Rapidly proliferating cells in the bone marrow and intestinal crypts are highly susceptible to chemotherapy, and damage to these cellular compartments may preclude maximally effective chemotherapy administration. Glucagon-like peptide (GLP)-2 is an enteroendocrine-derived regulatory peptide that inhibits crypt cell apoptosis after administration of agents that damage the intestinal epithelium. We report here that a human degradation-resistant GLP-2 analogue, h[Gly2]-GLP-2 significantly improves survival, reduces bacteremia, attenuates epithelial injury, and inhibits crypt apoptosis in the murine gastrointestinal tract after administration of topoisomerase I inhibitor irinotecan hydrochloride or the antimetabolite 5-fluorouracil. h[Gly2]-GLP-2 significantly improved survival and reduced weight loss but did not impair chemotherapy effectiveness in tumor-bearing mice treated with cyclical irinotecan. Furthermore, h[Gly2]-GLP-2 reduced chemotherapy-induced apoptosis, decreased activation of caspase-8 and -3, and inhibited poly(ADP-ribose) polymerase cleavage in heterologous cells transfected with the GLP-2 receptor. These observations demonstrate that the antiapoptotic effects of GLP-2 on intestinal crypt cells may be useful for the attenuation of chemotherapy-induced intestinal mucositis. PMID- 11212270 TI - Taxane-antibody conjugates afford potent cytotoxicity, enhanced solubility, and tumor target selectivity. AB - Paclitaxel (Taxol) is a chemotherapeutic agent that prevents disassembly of microtubular polymers, causing a growth arrest in the G2-M phase of the cell cycle and leading to apoptotic death. Paclitaxel has remarkable efficacy against fast-growing tumors but possesses major drawbacks, such as poor solubility and lack of tumor selectivity. Conversely, monoclonal antibodies usually have low therapeutic efficacy but are highly soluble and selectively target tumor markers overexpressed in cancer cells. Therefore, to improve the therapeutic index of taxanes as chemotherapeutics, the high toxicity of paclitaxel was combined with the high selectivity and solubility of monoclonal antibodies as targeting agents. We report the chemical coupling and characterization of paclitaxel-antibody conjugates for treatment of neuroectoderm-derived tumors. Paclitaxel-antibody conjugates afforded selective toxicity toward cells expressing the target marker and were more cytotoxic in vitro than equimolar concentrations of free paclitaxel or free paclitaxel plus free antibody. In an in vivo model of xenografted tumors, systemic administration of paclitaxel-antibody conjugates prevented tumor growth and prolonged survival of mice better than free drugs. In addition, paclitaxel antibody conjugates were highly soluble in water and stable at -20 degrees C for at least 3 months. These studies may lead to an increase or an improvement of the armamentarium and selectivity of cytotoxic agents. PMID- 11212271 TI - Granulocytic differentiation of human NB4 promyelocytic leukemia cells induced by all-trans retinoic acid metabolites. AB - The metabolism of all-trans retinoic acid (ATRA) has been reported to be partly responsible for the in vivo resistance to ATRA seen in the treatment of human acute promyelocytic leukemia (APL). However, ATRA metabolism appears to be involved in the growth inhibition of several cancer cell lines in vitro. The purpose of this study was to evaluate the in vitro activity of the principal metabolites of ATRA [4-hydroxy-retinoic acid (4-OH-RA), 18-hydroxy-retinoic acid (18-OH-RA), 4-oxo-retinoic acid (4-oxo-RA), and 5,6-epoxy-retinoic acid (5,6 epoxy-RA)] in NB4, a human promyelocytic leukemia cell line that exhibits the APL diagnostic t(15;17) chromosomal translocation and expresses the PML-RAR alpha fusion protein. We established that the four ATRA metabolites were indeed formed by the NB4 cells in vitro. NB4 cell growth was inhibited (69-78% at 120 h) and cell cycle progression in the G1 phase (82-85% at 120 h) was blocked by ATRA and all of the metabolites at 1 microM concentration. ATRA and its metabolites could induce NB4 cells differentiation with similar activity, as evaluated by cell morphology, by the nitroblue tetrazolium reduction test (82-88% at 120 h) or by the expression of the maturation specific cell surface marker CD11c. In addition, nuclear body reorganization to macropunctated structures, as well as the degradation of PML-RAR alpha, was found to be similar for ATRA and all of its metabolites. Comparison of the relative potency of the retinoids using the nitroblue tetrazolium reduction test showed effective concentrations required to differentiate 50% of cells in 72 h as follows: ATRA, 15.8 +/- 1.7 nM; 4-oxo-RA, 38.3 +/- 1.3 nM; 18-OH-RA, 55.5 +/- 1.8 nM; 4-OH-RA, 79.8 +/- 1.8 nM; and 5,6 epoxy-RA, 99.5 +/- 1.5 nM. The ATRA metabolites were found to exert their differentiation effects via the RAR alpha nuclear receptors, because the RAR alpha-specific antagonist BMS614 blocked metabolite-induced CD11c expression in NB4 cells. These data demonstrate that the principal ATRA Phase 1 metabolites can elicit leukemia cell growth inhibition and differentiation in vitro through the RAR alpha signaling pathway, and they suggest that these metabolites may play a role in ATRA antileukemic activity in vivo. PMID- 11212272 TI - Intratesticular transplantation of testicular cells from leukemic rats causes transmission of leukemia. AB - A rat T-cell leukemia model was used to study the safety of germ cell transplantation as a mean of preventing infertility in males undergoing gonadotoxic cancer treatment. Donor germ cells were harvested from the testes of terminally ill leukemic rats and were either used directly or cryopreserved and thawed before transplantation by rete testis microinjection. All rats transplanted with testicular cells from leukemic donors developed signs of terminal rat T-cell leukemia, whereas control animals remained healthy. Cryopreservation of the donor germ cells caused a 3- to 6-day delay in the terminal phase of leukemia. When a known number of leukemic cells were mixed with germ cells and microinjected into the testis, the rate of appearance of terminal leukemia was directly related to the number of transferred leukemic lymphoblasts. As few as 20 leukemic cells were able to cause a cancer relapse resulting in terminal leukemia 21 days after transplantation in three of five transplanted animals. Our results demonstrate that germ cell transplantation with the presently used techniques is not safe enough for clinical use. Improved methods for purging testicular specimens of cancer cells or totally new approaches with transient xenogenetic host models to detect contamination of malignant cells must be developed before this technique can be offered to patients without fear of disease relapse. PMID- 11212273 TI - Targeted delivery of tissue factor to the ED-B domain of fibronectin, a marker of angiogenesis, mediates the infarction of solid tumors in mice. AB - The selective thrombosis of tumor blood vessels, leading to the starvation and subsequent death of tumor cells, is an attractive anticancer strategy. Here we report that a fusion protein, consisting of an antibody fragment specific for the oncofoetal ED-B domain of fibronectin fused to the extracellular domain of tissue factor, selectively targets tumor blood vessels in vivo. Furthermore, this fusion protein mediates the complete and selective infarction of three different types of solid tumors in mice. At the highest doses administered, complete tumor eradication was observed in 30% of the mice treated without apparent side effects. These results are of therapeutic relevance because the ED-B domain of fibronectin, a naturally occurring marker of angiogenesis identical in mouse and man, is expressed in the majority of aggressive solid tumors but is undetectable in normal vessels and tissues. PMID- 11212274 TI - A photobiological and photophysical-based study of phototoxicity of two chlorins. AB - To understand the fundamental determinants of phototoxic efficacy and absorbed photodynamic dose, the triplet state and photobleaching quantum yields in living cells, cellular uptake, intracellular localization, and correlation with cell viability were studied for the two purpurins tin ethyl etiopurpurin 1 (SnET2) and tin octaethylbenzochlorin (SnOEBC) in ovarian cancer cells (OVCAR5). Although the triplet yields of these two photosensitizers were not significantly affected by cellular incorporation, the photobleaching yields were shown to be 3 orders of magnitude higher for cellular-bound sensitizer than for free or albumin-bound photosensitizer and higher for SnET2 than for SnOEBC for all of the cases. The intracellular concentration of SnOEBC was half that of SnET2 after 3 h- and 24 h incubation times for both 0.1 microM and 1.0 microM incubation concentrations. Despite the lower concentrations of SnOEBC, the phototoxicity of the two photosensitizers was comparable at 1-microM incubation concentration and was up to 10-fold higher for SnOEBC at the lower concentration. The subcellular localization established using confocal microscopy and molecular probes showed that both photosensitizers were primarily lysosomally localized. SnOEBC, however, had an extra-lysosomal, mitochondrial localization component. The photophysical measurements allowed calculation of the intracellular singlet oxygen production, which indicated that the photosensitizer-light dose reciprocity was limited by photobleaching for SnET2 but only minimally for SnOEBC, and this was confirmed through cell-survival studies. Taken together, these data indicate that the critical determinant of differences in phototoxicity between the two molecules was their relative rates of photobleaching and their subcellular localization. The study points to the importance of combining photosensitizer uptake and localization with photophysical measurements in the relevant biological milieu to reasonably interpret and/or predict photosensitization efficacies. PMID- 11212275 TI - Antiproliferative effects of S-allylmercaptocysteine on colon cancer cells when tested alone or in combination with sulindac sulfide. AB - Epidemiological studies link increased garlic (Allium sativum) consumption with a reduced incidence of colon cancer in various human populations. Experimental carcinogenesis studies in animal models and in cell culture systems indicate that several allium-derived compounds exhibit inhibitory effects and that the underlying mechanisms may involve both the initiation and promotion phases of carcinogenesis. To provide a better understanding of the effects of allium derivatives on the prevention of colon cancer, we examined two water-soluble derivatives of garlic, S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC), for their effects on proliferation and cell cycle progression in two human colon cancer cell lines, SW-480 and HT-29. For comparison, we included the compound sulindac sulfide (SS), because sulindac compounds are well-established colon cancer chemopreventive agents. We found that SAMC, but not SAC, inhibited the growth of both cell lines at doses similar to that of SS. SAMC also induced apoptosis, and this was associated with an increase in caspase3-like activity. These affects of SAMC were accompanied by induction of jun kinase activity and a marked increase in endogenous levels of reduced glutathione. Although SS caused inhibition of cell cycle progression from G1 to S, SAMC inhibited progression at G2-M, and a fraction of the SW-480 and HT-29 cells were specifically arrested in mitosis. Coadministration of SS with SAMC enhanced the growth inhibitory and apoptotic effects of SS. These findings suggest that SAMC may be useful in colon cancer prevention when used alone or in combination with SS or other chemopreventive agents. PMID- 11212276 TI - Differential p53-dependent mechanism of radiosensitization in vitro and in vivo by the protein kinase C-specific inhibitor PKC412. AB - The cellular response to ionizing radiation is governed by the DNA-damage recognition process but is also modulated by cytoplasmic signal transduction cascades that are part of the cellular stress response. Growth-promoting protein kinase C activity antagonizes irradiation-induced cell death, and, therefore, protein kinase C inhibitors might be potent radiosensitizers. The antiproliferative and radiosensitizing effect of the novel N-benzoylated staurosporine analogue PKC412 was tested in vitro against genetically defined p53 wild type (+/+) and p53-deficient (-/-) murine fibrosarcoma cells and in vivo against radioresistant p53-/- murine fibrosarcoma and human colon adenocarcinoma tumor xenograft (SW480, p53-mutated). PKC412 sensitized both p53+/+ and p53-/- tumor cells in vitro and in vivo for treatment with ionizing radiation but with a different mechanism of radiosensitization depending on the p53 status. In p53+/+, cells combined treatment with PKC412 and ionizing radiation drastically induced apoptotic cell death, whereas no apoptosis induction could be observed in p53 deficient cells in vitro and in histological tumor sections. Combined treatment resulted in an increased G2 cell cycle distribution in p53-/- cells at PKC412 concentrations that did not alter cell cycle distribution when applied alone. In vivo, a minimal treatment regimen during 4 consecutive days of PKC412 (4 x 100 mg/kg) in combination with ionizing radiation (4 x 3 Gy) exerted a substantial tumor growth delay for both p53-disfunctional tumor xenografts and showed that the clinically relevant protein kinase C inhibitor PKC412 is a promising new radiosensitizer with a potentially broad therapeutic window. PMID- 11212277 TI - The HER tyrosine kinase inhibitor CI1033 enhances cytotoxicity of 7-ethyl-10 hydroxycamptothecin and topotecan by inhibiting breast cancer resistance protein mediated drug efflux. AB - Because the activities of HER family members are elevated and/or aberrant in a variety of human neoplasms, these cell surface receptors are receiving increasing attention as potential therapeutic targets. In the present study, we examined the effect of combining the HER family tyrosine kinase inhibitor CI1033 (PD 183805) with the topoisomerase (topo) I poison 7-ethyl-10-hydroxycamptothecin (SN-38), the active metabolite of irinotecan, in a number of different cell lines. Colony forming assays revealed that the antiproliferative effects of simultaneous treatment with CI1033 and SN-38 were synergistic in T98G glioblastoma cells and HCT8 colorectal carcinoma cells, whereas sequential treatments were additive at best. In additional studies examining the mechanistic basis for these findings in T98G cells, immunoblotting revealed that the inhibitory effects of CI1033 on epidermal growth factor receptor autophosphorylation were unaffected by SN-38. Likewise, CI1033 had no effect on topo I polypeptide levels, localization, or activity. Nonetheless, CI1033 markedly enhanced the number of covalent topo I-DNA complexes stabilized by SN-38 or the related agent topotecan (TPT). Analysis of intracellular SN-38 levels by high-performance liquid chromatography and intracellular TPT levels by flow microfluorometry revealed that CI1033 increased the steady-state accumulation of SN-38 and TPT by 9.4 +/- 1.9- and 1.8 +/- 0.2 fold, respectively. Further evaluation revealed that the initial rate of TPT uptake was unaffected by CI1033, whereas the rate of efflux was markedly diminished. Additional studies demonstrated that T98G and HCT8 cells express the breast cancer resistance protein (BCRP), a recently cloned ATP binding cassette transporter. Moreover, CI1033 enhanced the uptake and cytotoxicity of SN-38 and TPT in cells transfected with BCRP but not empty vector. Conversely, CI1033 accumulation was diminished in cells expressing BCRP, suggesting that CI1033 is a substrate for this efflux pump. These results indicate that CI1033 can modulate the accumulation and subsequent cytotoxicity of two widely used topo I poisons in cells that have no history of previous exposure to these agents. PMID- 11212278 TI - In vitro and in vivo reversal of P-glycoprotein-mediated multidrug resistance by a novel potent modulator, XR9576. AB - The overexpression of P-glycoprotein (P-gp) on the surface of tumor cells causes multidrug resistance (MDR). This protein acts as an energy-dependent drug efflux pump reducing the intracellular concentration of structurally unrelated drugs. Modulators of P-gp function can restore the sensitivity of MDR cells to such drugs. XR9576 is a novel anthranilic acid derivative developed as a potent and specific inhibitor of P-gp, and in this study we evaluate the in vitro and in vivo modulatory activity of this compound. The in vitro activity of XR9576 was evaluated using a panel of human (H69/LX4, 2780AD) and murine (EMT6 AR1.0, MC26) MDR cell lines. XR9576 potentiated the cytotoxicity of several drugs including doxorubicin, paclitaxel, etoposide, and vincristine; complete reversal of resistance was achieved in the presence of 25-80 nM XR9576. Direct comparative studies with other modulators indicated that XR9576 was one of the most potent modulators described to date. Accumulation and efflux studies with the P-gp substrates, [3H]daunorubicin and rhodamine 123, demonstrated that XR9576 inhibited P-gp-mediated drug efflux. The inhibition of P-gp function was reversible, but the effects persisted for >22 h after removal of the modulator from the incubation medium. This is in contrast to P-gp substrates such as cyclosporin A and verapamil, which lose their activity within 60 min, suggesting that XR9576 is not transported by P-gp. Also, XR9576 was a potent inhibitor of photoaffinity labeling of P-gp by [3H]azidopine implying a direct interaction with the protein. In mice bearing the intrinsically resistant MC26 colon tumors, coadministration of XR9576 potentiated the antitumor activity of doxorubicin without a significant increase in toxicity; maximum potentiation was observed at 2.5-4.0 mg/kg dosed either i.v. or p.o. In addition, coadministration of XR9576 (6-12 mg/kg p.o.) fully restored the antitumor activity of paclitaxel, etoposide, and vincristine against two highly resistant MDR human tumor xenografts (2780AD, H69/LX4) in nude mice. Importantly all of the efficacious combination schedules appeared to be well tolerated. Furthermore, i.v. coadministration of XR9576 did not alter the plasma pharmacokinetics of paclitaxel. These results demonstrate that XR9576 is an extremely potent, selective, and effective modulator with a long duration of action. It exhibits potent i.v. and p.o. activity without apparently enhancing the plasma pharmacokinetics of paclitaxel or the toxicity of coadministered drugs. Hence, XR9576 holds great promise for the treatment of P-gp mediated MDR cancers. PMID- 11212279 TI - Pretreatment with paclitaxel enhances apo-2 ligand/tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of prostate cancer cells by inducing death receptors 4 and 5 protein levels. AB - We have demonstrated that Apo-2 ligand (Apo-2L)/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis of human prostate cancer PC 3, DU145, and LNCaP cells in a dose-dependent manner, with PC-3 cells displaying the greatest sensitivity to Apo-2L/TRAIL. Susceptibility of the prostate cancer cell types to Apo-2L/TRAIL-induced apoptosis did not appear to correlate with the levels of the Apo-2L/TRAIL receptors death receptor (DR) 4 (TRAIL receptor 1) or DR5 (TRAIL receptor 2), decoy receptor (DcR) 1 and DcR2, Flame-1, or the inhibitors of apoptosis proteins family of proteins. Apo-2L/TRAIL-induced apoptosis of PC-3 cells was associated with the processing of caspase-8, caspase 10, and the proapoptotic Bid protein, resulting in the cytosolic accumulation of cytochrome c as well as the processing of procaspase-9 and procaspase-3. Cotreatment with the caspase-8 inhibitor z-IETD-fmk or DR4:Fc significantly inhibited Apo-2L/TRAIL-induced apoptosis. Treatment with paclitaxel or taxotere increased DR4 and/or DR5 protein levels (up to 8-fold) without affecting the protein levels of DcR1 and DcR2, Apo-2L/TRAIL, Fas, or Fas ligand. Up-regulation of DR4 and DR5 was not preceded by the induction of their mRNA levels but was inhibited by cotreatment with cycloheximide. Importantly, sequential treatment of PC-3, DU145, and LNCaP cells with paclitaxel followed by Apo-2L/TRAIL induced significantly more apoptosis than Apo-2L/TRAIL treatment alone (P < 0.01). This was also associated with greater processing of procaspase-8 and Bid, as well as greater cytosolic accumulation of cytochrome c and the processing of caspase-3. These findings indicate that up-regulation of DR4 and DR5 protein levels by treatment with paclitaxel enhances subsequent Apo-2L/TRAIL-induced apoptosis of human prostate cancer cells. PMID- 11212280 TI - A truncated human xeroderma pigmentosum complementation group A protein expressed from an adenovirus sensitizes human tumor cells to ultraviolet light and cisplatin. AB - Individuals with the genetic disease xeroderma pigmentosum (XP) have impaired nucleotide excision repair (NER). Group A XP cells are defective in the XPA protein essential for NER and serve, together with other NER proteins, as a nucleation factor for the demarcation of bulky DNA damage. Because XPA cells are extremely sensitive to UV and drugs that cause bulky DNA damage, the XPA protein is an attractive target for manipulating cellular sensitivity to certain cancer therapeutics, a concept that perhaps can be applied toward developing more effective cancer treatments. We have made a replication-defective adenovirus, AdCMV-FlagXPA(59-114), that expresses a truncated form of XPA encompassing amino acids 59-114 sufficient for binding to the excision repair cross-complementing protein 1 (ERCC1)/xeroderma pigmentosum complementation group F (XPF) nuclease essential for making an incision 5' of the damage. On the basis of previous work, it was expected that this truncated XPA protein would work as a decoy and impair NER and, thus, sensitize cells to UV and drugs that produce bulky DNA lesions. Because the truncated XPA protein is "tagged" with the Flag epitope, an anti-Flag antibody can be used to detect protein expression and to isolate proteins associated with the XPA complex. We show that relatively large quantities of truncated XPA protein are present in infected human lung carcinoma A549 cells 2-4 days postinfection. Moreover, in a pull-down assay using anti-Flag antibody, we show that ERCC1 is present in the FlagXPA complex but not in a complex isolated from cells infected with a control virus. Most importantly, cells infected with AdCMV-FlagXPA(59-114) are significantly more sensitive than control cells to UV induced damage as determined by host-cell reactivation of UV-irradiated AdLacZ adenovirus and in a cytotoxicity assay that appears to be the result of aberrant processing of 6-4 photoproducts. Infected cells were also more sensitive to treatment with cisplatin, an important cancer drug. These results suggest that NER, and the XPA protein in particular, can be a direct target for sensitizing tumor cells to UV and cisplatin and perhaps also certain other clinically important drugs. PMID- 11212281 TI - Cumulative and irreversible cardiac mitochondrial dysfunction induced by doxorubicin. AB - Interference with mitochondrial calcium regulation is proposed to be a primary causative event in the mechanism of doxorubicin-induced cardiotoxicity. We previously reported disruption of mitochondrial calcium homeostasis after chronic doxorubicin administration (Solen et al. Toxicol. Appl. Pharmacol, 129: 214-222, 1994). The present study was designed to characterize the dose-dependent and cumulative interference with mitochondrial calcium regulation and to assess the reversibility of this functional lesion. Sprague Dawley rats were treated with 2 mg/kg/week doxorubicin s.c. for 4-8 weeks. With succinate as substrate, cardiac mitochondria isolated from rats after 4 weeks of treatment with doxorubicin expressed a lower calcium loading capacity compared with control. This suppression of calcium loading capacity increased with successive doses to 8 weeks of treatment (P < 0.05) and persisted for 5 weeks after the last doxorubicin injection, and was corroborated by dose-dependent and irreversible histopathological changes. Preincubation of mitochondria with tamoxifen, DTT, or monobromobimane did not reverse the diminished calcium loading capacity caused by doxorubicin. In contrast, incubation with cyclosporin A abolished any discernible difference in mitochondrial calcium loading capacity between doxorubicin-treated and saline-treated rats. The decrease in cardiac mitochondrial calcium loading capacity was not attributable to bioenergetic changes in the electron transport chain, because the mitochondrial coupling efficiency was not altered by doxorubicin treatment. However, the ADP/ATP translocase content was significantly lower in mitochondria from rats that received 8 weeks of doxorubicin treatment. These data indicate that doxorubicin treatment in vivo causes a dose-dependent and irreversible decrease in mitochondrial calcium loading capacity. Suppression of adenine nucleotide translocase content may be a key factor altering the calcium-dependent regulation of the mitochondrial permeability transition pore, which may account for the cumulative and irreversible loss of myocardial function in patients receiving doxorubicin chemotherapy. PMID- 11212282 TI - Nitrated and oxidized plasma proteins in smokers and lung cancer patients. AB - Cigarette smoking is a cause of lung cancer and other respiratory diseases. Oxidants either present in cigarette smoke and/or formed in the lung of smokers may trigger oxidative and nitrative damage to DNA and cellular components, contributing to carcinogenesis. We have used immunodot and Western blot analyses to measure nitrated (nitrotyrosine-containing) and oxidized (carbonyl-containing) proteins in plasma samples collected from 52 lung cancer patients and 43 control subjects (heavy and light smokers, nonsmokers with or without exposure to environmental tobacco smoke). The levels of nitrated proteins were significantly higher in lung cancer patients than in controls (P = 0.003). On the other hand, the levels of oxidized proteins were significantly higher in smokers than in nonsmokers (P < 0.001). Western-blot analyses showed the presence of two to five nitrated proteins and one oxidized protein. Using immunoprecipitation and Western blot analyses with eight different antibodies against human plasma proteins, we identified fibrinogen, transferrin, plasminogen, and ceruloplasmin as nitrated proteins and fibrinogen as the only oxidized protein present in human plasma of lung cancer patients and smokers. Our results indicate that cigarette smoking increases oxidative stress and that during lung cancer development, formation of reactive nitrogen species results in nitration and oxidation of plasma proteins. PMID- 11212283 TI - Building a multigenic model of breast cancer susceptibility: CYP17 and HSD17B1 are two important candidates. AB - We conducted a nested case-control study to evaluate whether polymorphisms in two genes involved in estrogen metabolism, CYP17 and HSD17B1, were useful in developing a breast cancer risk model that could help discriminate women who are at higher risk of breast cancer. If polymorphisms in these genes affect the level of circulating estrogens, they may directly influence breast cancer risk. The base population for this study is a multiethnic cohort study that includes African-American, Non-Latina White, Japanese, Latina, and Native Hawaiian women. For this analysis, 1508 randomly selected controls and 850 incident breast cancer cases of the first four ethnic groups who agreed to provide a blood specimen were included (76 and 80% response rates, respectively). The CYP17 A2 allele and the HSD17B1 A allele were considered "high-risk" alleles. Subjects were then classified according to number of high-risk alleles. After adjusting for age, weight, and ethnicity, we found that carrying one or more high-risk alleles increases the risk of advanced breast cancer in a dose-response fashion. The risk among women carrying four high-risk alleles was 2.21 [95% confidence interval (CI), 0.98-5.00; P for trend = 0.03] compared with those who carried none. This risk was largely limited to women who were not taking hormone replacement therapy (relative risk, 2.60; 95% CI, 0.95-7.14) and was most pronounced among those weighing 170 pounds or less (RR, 3.05; 95% CI, 1.29-7.25). These findings suggest that breast cancer risk has a strong genetic component and supports the theory that the underlying mechanism of "complex traits" can be understood using a multigenic model of candidate genes. PMID- 11212284 TI - Cyclohexane as an alternative vapor of carbon tetrachloride for the assessment of gas removing capacities of gas masks. AB - An alternative vapor was explored to replace carbon tetrachloride (CCl4) for testing breakthrough times of cartridges and canisters of gas masks in the National Approval Test of Respirators. Cyclohexane was single out as a candidate for the alternative vapor out of six vapors: trichloroethylene, n-pentane, n hexane, n-heptane, toluene and cyclohexane from the viewpoints of similarity of vapor pressure and water-solubility to CCl4, lower toxicity than CCl4, and technical feasibility in generating an airflow of 30 L/min containing the vapor ranging from 300 to 5000 ppm. Breakthrough times of cartridges and canisters were examined by generating cyclohexane vapor in a test airflow of 30 L/min in comparison with CCl4 vapor under various test conditions with different vapor concentrations and relative humidities (RH). As the results, the breakthrough times of the cartridges and canisters for cyclohexane were found to almost coincide with those for CCl4 under all examined range of concentrations and RH. By an increase of humidity from 50% RH to 80% RH, the cartridges showed significant shortening of breakthrough times for both of CCl4 and cyclohexane, but the susceptibility of the breakthrough time of cyclohexane to humidity was also similar to that of CCl4. It was, therefore, concluded that cyclohexane can be recommended as the alternative vapor of CCl4 for testing the breakthrough times of gas mask cartridges and canisters in the National Approval Test. PMID- 11212285 TI - Hematocrit and risk for hypertension in middle-aged Japanese male office workers. AB - The association of hematocrit with development of hypertension over 9 years was studied in 784 hypertension-free Japanese men aged 40 to 59 years. The age adjusted relative risk for hypertension above the borderline level and definite hypertension increased in a dose-dependent manner as hematocrit level increased (P for trend: 0.007 and 0.001, respectively). After controls for other potential factors of hypertension, the test for trend across increasing categories of hematocrit level remained as statistical significance for definite hypertension (P=0.015). The multivariate-adjusted relative risk for definite hypertension compared with less than 43.8% of hematocrit level was 1.29 [95% confidence interval (CI): 0.62-2.67] for 43.8 to 45.2% hematocrit level, 1.35 (95% CI: 0.62 2.95) for 45.3 to 46.3% hematocrit level, 1.96 (95% CI: 0.97-3.97) for 46.4 to 48.1% hematocrit level, and 2.06 (95% CI: 1.02-4.15) for 48.2% or more hematocrit level. These results suggest that hematocrit is closely associated with development of hypertension in middle-aged Japanese men. PMID- 11212286 TI - Effect of platinum coordination complex (PtCx) on citrate uptake by rat renal brush border membrane vesicles (BBMV): direct effect of carboplatin. AB - Inhalation of platinum, as soluble salts, is known to cause respiratory distress and severe dermatitis in workers. Platinum coordination complexes are widely used in the treatment of a variety of solid tumors. However, the clinical use of cisplatin (CDDP) (the most useful agent) is limited by the development of nephrotoxicity. High dose accidental exposure to soluble platinum in platinum refineries and pharmaceutical factories could induce occupational nephrotoxicity. Carboplatin (CBDCA), a second-generation platinum coordination complex, is highly effective against a variety of malignancies at doses five- to ten-times higher than CDDP. At therapeutic doses, CBDCA is less nephrotoxic than CDDP. Additionally, urinary citrate is freely filtered at the glomerulus, and its reabsorption in the proximal tubule is the major determinant of the rate of renal excretion. In our previous study, the preincubation of rat renal brush border membrane vesicles (BBMV) with 5 mM cisplatin for 4 and 8 hours significantly inhibited the citrate uptake compared with that of the control BBMV. In this study, we exposed BBMV to 100 mM carboplatin (twenty-times higher concentration than cisplatin) and examined the citrate uptake characteristics to clarify the toxic mechanism of platinum coordination complexes. The preincubation of BBMV with 100 mM carboplatin for 8 hours also significantly inhibited the citrate uptake compared with that of the control BBMV, but the alterations were not as severe as those with 5 mM cisplatin. PMID- 11212287 TI - Association of alcohol consumption with increase in aortic stiffness: a 9-year longitudinal study in middle-aged Japanese men. AB - A 9-year longitudinal study was performed to prospectively examine the association of alcohol consumption with development of aortic stiffness in 1121 aortic stiffness-free [aortic pulse wave velocity (PWV) of less than 8.0 m/sec] Japanese men aged 35 to 59 years without definite hypertension, hypercholesterolemia, or diabetes. 274 men developed aortic stiffness (aortic PWV of 8.0 m/sec or more) during 8872 person-years follow-up. After controlling for potential predictors of aortic stiffness, the relative risk for increased aortic stiffness compared with non-drinkers was 1.01 [95% confidence interval (CI): 0.62 1.64] for those who drank 0.1 to 22.9 g/day of ethanol, 1.71 (95% CI: 1.12-2.60) for those who drank 23.0 to 45.9 g/day of ethanol, 1.79 (95% CI: 1.18-2.71) for those who drank 46.0 to 68.9 g/day of ethanol, and 2.09 (95% CI: 1.35-3.26) for those who drank 69.0 or more g/day of ethanol (P for trend < 0.001). These results suggest that alcohol consumption is closely associated with development of aortic stiffness. PMID- 11212288 TI - Lymphocyte metallothionein-mRNA as a sensitive biomarker of cadmium exposure. AB - Human peripheral blood lymphocytes (PBLs) produce metallothioneins (MTs) in response to a variety of heavy metal ions. MTs could therefore be a candidate for a marker that represents the biological effect of heavy metals. Since it is practically difficult to measure MT protein levels in PBLs, we examined if MT mRNA could serve as a biomarker of heavy metal exposure. It is difficult to obtain RNA from PBLs without degradation, but we found that intact RNA can be prepared by the acid guanidinium thiocyanate-phenol-chloroform extraction method which minimizes nuclease digestion of RNA during purification steps. By Northern blot analysis of RNA isolated by this method from PBLs cultured with or without CdSO4, we demonstrated that MT-mRNA is induced by 0.1 to 0.5 microM CdSO4 in a dose-dependent manner. The blood cadmium levels of exposed humans have been reported to be up to 0.5 microM. This suggests that our assay is able to detect quantitative changes in the PBL MT-mRNA level resulting from in vivo cadmium exposure. Thus, PBL MT-mRNA could be used as a sensitive biomarker reflecting exposure to cadmium, and probably to several other MT-inducing heavy metals. PMID- 11212289 TI - Causal relationship between a case of severe hepatic dysfunction and low exposure concentrations of N,N-dimethylformamide in the synthetics industry. AB - A 19-year-old man suffered hepatic dysfunction after 5 months of exposure to N,N dimethylformamide (DMF) at his job in the synthetic resins industry. Laboratory data revealed elevated levels of AST (578 IU/l), ALT (1193 IU/l), and gamma-GTP (107 IU/l), no viral infection with HAV, HBV, or HCV, and no history or evidence of hepatic injury, although he did have a slight abdominal abnormality and swelling which was detected by palpation. His urinary N-methylformamide level, as a biological exposure index of DMF, was 42.8 mg/l, indicating 10-30 ppm of DMF exposure. After 2 months he was reinstated in two workplaces, the former where he worked in the morning and the other in the afternoon where environmental DMF concentrations were less than those in the former workplace. On the 18th day after his reinstatement, his liver function became exasperated again. After the second period of medication and one month of rest from work, he had fully recovered and was reinstated, but to a workshop without DMF exposure. PMID- 11212290 TI - Lung lesions induced by intratracheal instillation of vanadium pentoxide powder in rats. AB - To clarify acute toxicity and histopathological changes in the lung after exposure to V2O5 powder, rats (SD, male, n=66) were observed for 4 weeks after an intratracheal administration of V2O5 powder (geometric mean diameter 0.31 microm, geomertic standard deviation sigmag=2.19) at three doses (0.88, 3.0, 13.0 mg/kg body weight). The histopathological lung lesions were developed dose-dependently, and characterized by exudative inflammation, injury of alveolar macrophages, and swelling and mucous degeneration in the broncho-bronchiolar epithelia. Growth rate of the V2O5 powder-instilled rat was also retarded dose-dependently. The V2O5 powder used was composed of not coagulated but well dispersed particles consisting of vanadium pentoxide of more than 99.8% (w/w) with vanadium tetraoxide of less than 0.2%. The V2O5 powder was found to be 8 times more soluble in an artificial biological fluid "Gamble's solution" than in a pure water. From the present findings as well as those from the related literature, it was inferred that the histopathological lesions induced by the intratracheally instilled V2O5 powder are caused not only by the V2O5 particles per se but also by vanadium ions dissolved from the particles into the lung fluid. PMID- 11212291 TI - Hepatocyte growth factor in renal disease: cause or cure? AB - Hepatocyte growth factor (HGF) is an injury-released growth factor with diverse effects on epithelial and endothelial cells. These effects include proliferation, migration, extracellular matrix production and tubulogenesis. These activities allow HGF to function as an organizer of repair processes that bring about restoration of tubular function following renal injury. However, while HGF has been demonstrated to accelerate recovery of renal function after an acute insult, prolonged exposure to elevated levels of HGF can reduce renal function and may contribute to progressive renal disease. This review will describe the cellular activities of HGF, how they pertain to renal repair and the therapeutic application of regulating HGF activity in acute versus chronic renal disease. PMID- 11212292 TI - Bacterial suicide through stress. AB - Outside of the laboratory, bacterial cells are constantly exposed to stressful conditions, and an ability to resist those stresses is essential to their survival. However, the degree of stress required to bring about cell death varies with growth phase, amongst other parameters. Exponential phase cells are significantly more sensitive to stress than stationary phase ones, and a novel hypothesis has recently been advanced to explain this difference in sensitivity, the suicide response. Essentially, the suicide response predicts that rapidly growing and respiring bacterial cells will suffer growth arrest when subjected to relatively mild stresses, but their metabolism will continue: a burst of free radical production results from this uncoupling of growth from metabolism, and it is this free-radical burst that is lethal to the cells, rather than the stress per se. The suicide response hypothesis unifies a variety of previously unrelated empirical observations, for instance induction of superoxide dismutase by heat shock, alkyl-hydroperoxide reductase by osmotic shock and catalase by ethanol shock. The suicide response also has major implications for current [food] processing methods. PMID- 11212293 TI - Modulation of phospholipase A2 activity generated by molecular evolution. AB - Snake venom oligomeric neurotoxins offer several unique examples of modulation of phospholipase A2 (PLA2) activity generated by molecular evolution. This phenomenon was found in evolutionary younger snakes and is probably common for representatives of the genus Vipera. At present, the best-studied example is the heterodimeric neurotoxin vipoxin from the venom of the southeast European snake Vipera ammodytes meridionalis. It is a complex between a basic strongly toxic PLA2 and an acidic and catalytically inactive PLA2-like component (Inh). This is the first reported example of a high degree of structural homology (62%) between an enzyme and its natural protein inhibitor. The inhibitor is a product of the divergent evolution of the unstable PLA2 in order to stabilize it and to preserve the pharmacological activity/toxicity for a long time. Inh reduces both the catalytic activity and toxicity of PLA2. Vipoxin also illustrates evolution of the catalytic into a inhibitory function. Vipoxin analogues have been found in the venom of viperid snakes inhabiting diverse regions of the world. An attempt is made to explain modulation of the toxic function by the three-dimensional structure of vipoxin. PMID- 11212294 TI - Cryo-bioorganic chemistry: molecular interactions at low temperature. AB - Freezing of aqueous or organic solutions plays a pivotal role in enhancement of rate and/or yield of biomolecular reactions. The smooth conditions of the frozen state at low temperature can also suppress racemization and side-product formation of the reactions. Molecular interactions in liquid undercooled solutions, on the other hand, offer the possibility to study enzyme activity mechanisms in vitro and a chance for survival of organisms in vivo. This review illustrates the differences between frozen and liquid conditions on several small and large biomolecules, together with the synthetic use of freezing. In relation to the freezing effect on enzyme activity, a peculiar phenomenon is discussed: 'cryo-oscillations' are temporal motions of trypsin activity in frozen solution in the presence of Mn2+ ion. The molecular basis of cold adaptation is also discussed, which points to mechanisms evolved by organisms living at subzero temperatures. The factors involved in the freezing effect are shown; i.e. the role of freeze-concentration and frozen solvent surface is demonstrated and elucidated using several examples. PMID- 11212295 TI - Molecular mechanism of heme signaling in yeast: the transcriptional activator Hap1 serves as the key mediator. AB - Heme is a key molecule in mediating the effects of oxygen on various molecular and cellular processes in many living organisms. In the yeast Saccharomyces cerevisiae, heme serves as a secondary signal for oxygen; intracellular heme synthesis directly correlates with oxygen tension in the environment. In yeast, oxygen sensing and heme signaling are primarily mediated by the heme activator protein Hap1, which, in response to heme, activates the transcription of genes required for respiration and for controlling oxidative damage. Heme regulation of many genes required for anaerobic growth is mediated by the aerobic repressor Rox1, whose expression is controlled by heme. In this review, we summarize recent knowledge about (i) how heme synthesis may be controlled by oxygen tension, (ii) how heme precisely and stringently controls Hap1 activity and (iii) whether other transcriptional activators can also mediate heme action. PMID- 11212296 TI - Integrin antagonists. AB - Integrins are a family of cell surface glycoproteins that mediate numerous cell cell and cell-matrix interactions and are involved in biological processes such as tissue morphogenesis, leukocyte recirculation and migration, wound healing, blood clotting and immune response. Aberrant cell adhesion has been implicated in the pathogenesis of several diseases, including a number of inflammatory disorders such as rheumatoid arthritis, inflammatory bowel disease and asthma, as well as cancer and coronary heart disease. As such integrins are seen as excellent targets for the development of therapeutic agents. This report begins with an examination of the structure of integrin molecules and their ligands and then goes on to review the current state of development of antiintegrin antagonists. PMID- 11212297 TI - Laminins during muscle development and in muscular dystrophies. AB - Cellular interactions with the extracellular matrix during muscle formation and in muscular dystrophy have received increased interest during the past years. Laminins constitute a growing family of proteins with complex expression patterns in forming basement membranes during muscle development. In skeletal muscle, laminins constitute major ligands for cell surface receptors involved in the transmission of force from the cell interior, but laminins might also influence signal transmission events during muscle formation and in muscle regeneration. During myogenesis the laminin alpha1 chain is present around the epithelial somite; but later, in forming muscle, the laminin alpha1 chain is restricted to the myotendinous junction. The laminin alpha2, alpha4 and alpha5 chains are major laminin chains in the muscle basement membrane during muscle formation, but laminin alpha4 and alpha5 chains are absent in adult muscle. The importance of laminins for muscle integrity is manifested in congenital muscular dystrophies with defects in the laminin alpha2 chain. There is no good evidence for the presence of laminin alpha1 chain in dystrophic muscle, but some other fetal muscle laminins can be detected in dystrophic muscle. Characterization of laminin expression patterns in muscular dystrophies might be of diagnostic and therapeutic value. In this paper, we review the recent publications on the biological functions of muscle laminins and discuss their roles in skeletal muscle. PMID- 11212298 TI - Roles of postsynaptic density-95/synapse-associated protein 90 and its interacting proteins in the organization of synapses. AB - Synapses are central stages for neurotransmission. Neurotransmitters are released from the presynaptic membrane of one neuron, and bind to the receptors accumulated at the postsynaptic membrane, followed by the activation of the other neuron. The strength of a synapse is modified depending on the history of the previous neurotransmissions. This property is called synaptic plasticity and is implicated in learning and memory. Synapses contain not only the components essential for neurotransmission but also the signalling molecules involved in synaptic plasticity. The elucidation of the molecular structures of synapses is one of the key steps to understand the mechanism of learning and memory. Recent studies have revealed postsynaptic density (PSD)-95/synapse-associated protein (SAP) 90 as a core component in the architecture of synapses. In this review, we summarize up-to-date information about PSD-95/SAP90 and its interacting proteins, and the organization of synapses orchestrated PMID- 11212299 TI - The hypocretins/orexins: novel hypothalamic neuropeptides involved in different physiological systems. AB - The hypothalamus regulates diverse physiological functions, including the control of energy metabolism, circadian rhythms, stress and anxiety, sexual and reproductive behaviors. An overview of the most prevalent hypothalamus-enriched mRNAs revealed that this area of the brain specializes in producing intercellular signaling molecules. Two new secreted peptides derived from a single neuropeptide precursor, named hypocretins and orexins by two different groups, are synthesized in a small set of neurons in the perifornical area of the hypothalamus. Intracerebroventricular injection of the hypocretins/orexins increases food consumption in rats. Here we review recent progress in identifying the role of the hypocretins/orexins in the control of energy balance and in other physiological systems. PMID- 11212300 TI - Chemotherapy and immunotherapy of malignant glioma: molecular mechanisms and clinical perspectives. AB - Despite the considerable progress in modern tumor therapy, the prognosis for patients with glioblastoma, the most frequent malignant brain tumor, has not been substantially improved. Although cytoreductive surgery and radiotherapy are the mainstays of treatment for malignant glioma at present, novel cytotoxic drugs and immunotherapeutic approaches hold great promise as effective weapons against these malignancies. Thus, great efforts are being made to enhance antitumoral efficacy by combining various cytotoxic agents, by novel routes of drug administration, or by combining anticancer drugs and immune modulators. Immunotherapeutic approaches include cytotoxic cytokines, targeted antibodies, and vaccination strategies. However, the success of most of these experimental therapies is prevented by the marked molecular resistance of glioma cells to diverse cytotoxic agents or by glioma-associated immunosuppression. One promising experimental strategy to target glioma is the employment of death ligands such as CD95 (Fas/Apo1) ligand or Apo2 ligand (TRAIL). Specific proapoptotic approaches may overcome many of the obvious obstacles to a satisfactory management of malignant brain tumors. PMID- 11212301 TI - Carbamoyl phosphate synthetase: an amazing biochemical odyssey from substrate to product. AB - Carbamoyl phosphate synthetase (CPS) catalyzes one of the most remarkable reactions ever described in biological chemistry, in which carbamoyl phosphate is produced from one molecule of bicarbonate, two molecules of Mg2+ ATP, and one molecule of either glutamine or ammonia. The carbamoyl phosphate so produced is utilized in the synthesis of arginine and pyrimidine nucleotides. It is also employed in the urea cycle in most terrestrial vertebrates. Due to its large size, its important metabolic role, and the fact that it is highly regulated, CPS has been the focus of intensive investigation for nearly 40 years. Numerous enzymological, biochemical, and biophysical studies by a variety of investigators have led to a quite detailed understanding of CPS. Perhaps one of the most significant advances on this topic within the last 2 years has been the successful X-ray crystallographic analysis of CPS from Escherichia coli. Quite unexpectedly, this structural investigation revealed that the three active sites on the protein are widely separated from one another. Furthermore, these active sites are connected by a molecular tunnel with a total length of approximately 100 A, suggesting that CPS utilizes this channel to facilitate the translocation of reaction intermediates from one site to another. In this review, we highlight the recent biochemical and X-ray crystallographic results that have led to a more complete understanding of this finely tuned instrument of catalysis. PMID- 11212302 TI - Signaling through beta-catenin and Lef/Tcf. AB - Beta-catenin plays a structural role in cell adhesion by binding to cadherins at the intracellular surface of the plasma membrane and a signaling role in the cytoplasm as the penultimate downstream mediator of the wnt signaling pathway. The ultimate mediator of this pathway is a nuclear complex of beta-catenin acting as a coactivtor with lymphoid enhancer factor/T cell factor (Lef/Tcf) transcription factors to stimulate transcription of a variety of target genes. Signaling through beta-catenin is regulated by modulating its degradation and nuclear translocation. In the absence of an activating signal, phosphorylation of beta-catenin by glycogen synthase kinase 3 (GSK3) acting in conjunction with adenomatous polyposis coli and axin/conductin causes beta-catenin to interact with the beta-transducin repeat-containing protein which results in its ubiquitination and degradation. Signaling from the wnt pathway activates dishevelled which, in an as yet undefined manner, inhibits the activity of GSK3 resulting in an increase in the cytoplasmic free pool of beta-catenin, and translocation into the nucleus. The integrin-linked kinase (ILK) pathway also activates beta-catenin-Lef/Tcf signaling. ILK phosphorylates GSK3 to inhibit its activity and translocates beta-catenin into the nucleus. In addition, ILK downregulates the expression of E-cadherin and upregulates Lef-1 expression. In the final step of the beta-catenin-Lef/Tcf signaling pathway, nuclear beta catenin binds pontin52-TATA binding protein and displaces Groucho-related gene or CREB-binding protein corepressors from Lef/Tcf resulting in stimulation of transcription. During development, beta-catenin-Lef/Tcf signaling is involved in the formation of dorsal mesoderm and dorsal axis. Furthermore, defects in the beta-catenin-Lef/Tcf pathway are involved in the development of several types of cancers. PMID- 11212303 TI - Role of pathways for signal transducers and activators of transcription, and mitogen-activated protein kinase in adipocyte differentiation. AB - Members of the signal transducer and activator of transcription (STAT) family and the mitogen-activated protein kinase (MAPK) cascade play a major role in the regulation of cell growth and differentiation. This review concentrates on the role played by these pathways in the development of adipose cells. STATs are activated by both positive and negative modulators of adipocyte differentiation leading to the hypothesis that the STAT pathway may function in adipogenesis. The role of the p42/p44 MAPK pathway in adipocyte differentiation has recently been the subject of contradictory reports. Several molecular mechanisms are proposed to explain the opposing effects of MAPK activation in the programme of adipose cell differentiation. PMID- 11212304 TI - The in vitro antiapoptotic effect of dehydroepiandrosterone sulfate in mouse thymocytes and its relation to caspase-3/caspase-6. AB - The effects of dehydroepiandrosterone sulfate (DHEAS) on thymocyte apoptosis induced by dexamethasone (DEX) were investigated. Apoptosis was measured by using agarose gel electrophoresis of DNA, the terminal deoxynucleotidyltransferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay and flow cytometry. Our results showed that preincubation with 1 x 10(-4) M DHEAS protected thymocytes from DEX-induced apoptosis in vitro. Moreover, we found no blocking effect on the DEX-induced activation of caspase-3 and caspase-6 by the preincubation of thymocytes with DHEAS. This may be interpreted to mean that the antagonism of DHEAS to DEX-induced apoptosis is not related to the activation of these down stream caspases which play a critical role in the execution of apoptosis. PMID- 11212305 TI - Nitric oxide and cellular respiration. AB - The role of nitric oxide (NO) as a signalling molecule involved in many pathophysiological processes (e.g., smooth muscle relaxation, inflammation, neurotransmission, apoptosis) has been elaborated during the last decade. Since NO has also been found to inhibit cellular respiration, we review here the available information on the interactions of NO with cytochrome c oxidase (COX), the terminal enzyme of the respiratory chain. The effect of NO on cellular respiration is first summarized to present essential evidence for the fact that NO is a potent reversible inhibitor of in vivo O2 consumption. This information is then correlated with available experimental evidence on the reactions of NO with purified COX. Finally, since COX has been proposed to catalyze the degradation of NO into either nitrous oxide (N2O) or nitrite, we consider the putative role of this enzyme in the catabolism of NO in vivo. PMID- 11212306 TI - Kainate receptor pharmacology and physiology. AB - Glutamate is the primary neurotransmitter in the central nervous system. One of the classes of ionotropic glutamate receptors is kainate receptors. Recent developments in the pharmacology of kainate receptors have resulted in the emergence of several selective agonists and antagonists. These compounds have allowed scientists to begin to probe the functional properties of these receptors in neurons and gain a better understanding of the role of these receptors in the nervous system. PMID- 11212308 TI - Scaffolding proteins and their role in viral assembly. AB - Scaffolding proteins are proteins that are required to catalyse, regulate or modulate some step in the assembly of a macromolecular complex. They associate specifically with the nascent protein complex during assembly, but are subsequently removed, and are absent from the mature structure. Scaffolding proteins have been described primarily from viral systems, in particular from the double-stranded DNA bacteriophages, but most likely play a more general role in macromolecular assembly, a fundamental process in all biological systems. Scaffolding proteins may act in a specific fashion, by actively encouraging the formation of correct protein-protein interactions, or more generally by nucleating and promoting assembly. They may also work to ensure the fidelity of the assembly process by preventing the formation of improper interactions, in many ways similar to the role of molecular chaperones in protein folding. In viruses, scaffolding proteins are found both in the form of internal cores and external bracing, and may form elaborate and complex structures. This review will focus on the viral scaffolding proteins, for which an increasing amount of structural and functional information has recently become available. PMID- 11212307 TI - The polycystins: a novel class of membrane-associated proteins involved in renal cystic disease. AB - Polycystin-1, polycystin-2 and polycystin-L are the predicted protein products of the PKD1, PKD2 and PKDL genes, respectively. Mutations in PKD1 and PKD2 are responsible for almost all cases of autosomal dominant polycystic kidney disease (ADPKD). This condition is one of the commonest mendelian disorders of man with a prevalence of 1:800 and is responsible for nearly 10% of cases of end-stage renal failure in adults. The cloning of PKD1 and PKD2 in recent years has provided the initial steps in defining the mechanisms underlying renal cyst formation in this condition, with the aim of defining pharmacological and genetic interventions that may ameliorate the diverse and often serious clinical manifestations of this disease. The PKD genes share regions of sequence similarity, and all predictintegral membrane proteins. Whilst the predicted protein domain structure of polycystin-1 suggests it is involved in cell-cell or cell-matrix interactions, the similarity of polycystin-2 and polycystin-L to the pore-forming domains of some cation channels suggests that they all form subunits of a large plasma membrane ion channel. In the few years since the cloning of the PKD genes, a consensus that defines the range of mutations, expression pattern, interactions and functional domains of these genes and their protein products is emerging. This review will therefore attempt to summarise these data and provide an insight in to the key areas in which polycystin research is unravelling the mechanisms involved in renal cyst formation. PMID- 11212309 TI - Nickel-binding proteins. AB - Nickel enzymes are a relatively new class of metalloenzymes. The seven known nickel enzymes are urease, hydrogenase, CO-dehydrogenase, methyl-coenzyme M reductase, Ni-superoxide dismutase, glyoxalase I and cis-trans isomerase. The requirement for nickel implies the presence of a nickel-processing system, since free transition metals are harmful to the cell. A nickel-processing system involves the recognition and transport of nickel into the cell and the handling of the nickel once it enters the cell until it is inserted into the nickel enzyme. Several mechanisms for nickel transport have been identified and will be reviewed here. Accessory proteins required for the biosynthesis of the nickel active site have been identified. Accessory proteins bind the nickel when it enters the cell and are proposed to assist with the insertion of nickel into the enzyme. The function of the characterized nickel-processing proteins is described, and models for nickel insertion into the nickel enzymes are presented. PMID- 11212310 TI - Diagnostic and therapeutic applications of azulenyl nitrone spin traps. AB - Azulenyl nitrones have been recently demonstrated to constitute a new class of nitrone-based spin traps with the unprecedented capacity to tag free radicals by yielding characteristically colored and highly visible diamagnetic (and paramagnetic) spin adducts. In addition, a comparison of the oxidation potentials of azulenyl nitrones such as 1 and congeners to those of conventional nitrone spin traps previously investigated as potential antioxidant therapeutics such as N-tert-butyl-alpha-phenylnitrone and its related ortho-sodium sulfonate reveals that the azulene-derived spin traps are far more readily oxidized. These special features render azulenyl nitrones of interest with regard to both their distinct ability to engender the convenient use of colorimetric detection to monitor free radical-mediated oxidative stress in biological systems, and to their potentially enhanced efficacy as neuroprotective antioxidants vs. those conventional nitrone spin traps earlier examined as such. Herein is reported an overview of recent developments pertaining to the use of azulenyl nitrones in the detection of oxidative stress in animal models of amyotrophic lateral sclerosis and stroke, and to their neuroprotective activity in animal models of Parkinson's disease, stroke and neurodegeneration within the retina. PMID- 11212311 TI - Sexual behavior mutants revisited: molecular and cellular basis of Drosophila mating. AB - The study of Drosophila melanogaster by a combination of forward genetics with specific mutants, and reverse genetics, in which a given gene is expressed in an appropriate brain area to test its effect on behavior, provides a unique opportunity to explore the causal relationship between a particular gene, its function in the cell and the behavioral outcome at the organismic level. Enhanced male-to-male courtship has been shown to occur as a result of mutations in several different genes. For example, the Voila mutant exhibits intense GAL4 reporter expression in the tarsal gustatory sensilla, suggesting the importance of tapping by a male on the female abdomen with his forelegs. Feminization of parts of the antennal lobe and mushroom body by targeted expression of a female determining gene transformer+ (tra+) drives the male to court other males. Mutations in the tra target gene fruitless (fru), which is expressed in the antennal lobe as well as the suboesophageal ganglion (the gustatory inputs are processed here), also induce homosexual courtship in males. These results suggest that sensory inputs mediated and/or processed by the tarsal receptors, suboesophageal ganglion, antennal lobe and mushroom body contribute to the regulation of male-female courtship. Mosaic analysis localized the neural center for male courtship behavior to the posterior dorsal brain, in which the sensory information processed by the aforementioned neural structures may be integrated. Another mosaic study mapped the neural center for female sexual behavior, as measured by her receptiveness to copulation, to the anterior dorsal brain. The issue as to how the mutations that reduce female sexual receptiveness, e.g. dissatisfaction (dsf), spinster (spin) and chaste (cht), affect the structure and/or function of this neural center deserves to be addressed urgently. PMID- 11212312 TI - Vertebrate odorant receptors. AB - Olfactory transduction begins with the binding of an odorous molecule to a protein receptor--odorant receptor--on the cell surface of olfactory neuron. Odorant receptors are encoded by a large gene family belonging to the superfamily of G-protein-coupled, seven-transmembrane-domain receptors. Since the identification of the receptor gene family in 1991, a considerable amount of progress has been made in the study of odorant receptors, including aspects of spatial and temporal expression pattern, the genomic organization of the receptor genes, regulation of expression, and receptor function. These studies are of critical importance in understanding how the olfactory system recognizes and distinguishes thousands of odors. PMID- 11212313 TI - Three for T: molecular analysis of the low voltage-activated calcium channel family. AB - Despite the wealth of information on voltage-gated calcium channels, little is known about low voltage-activated, T-type channels. The ability of the antihypertensive drug mibefradil to selectively block T-type channels has generated much interest in their structure, physiology and pharmacology. This review covers the cloning of a new family of calcium channels, their putative structure, the electrophysiological evidence that demonstrated that these complementary DNAs encoded low voltage-activated, T-type channels, the tissue expression of these genes, and concludes with a discussion of their possible physiological roles. PMID- 11212314 TI - Hyaluronan synthases: fascinating glycosyltransferases from vertebrates, bacterial pathogens, and algal viruses. AB - Hyaluronan (or hyaluronic acid or hyaluronate; HA) is a polysaccharide found in the extracellular matrix of vertebrate tissues and in the surface coating of certain Streptococcus and Pasteurella bacterial pathogens. At least one algal virus directs its host to produce HA on the cell surface early in infection. HA synthases (HASs) are the enzymes that polymerize HA using uridine diphospho-sugar precursors. In all known cases, HA is secreted out of the cell; therefore, HASs are normally found in the outer membranes of the organism. In the last 6 years, the HASs have been molecularly cloned from all the above sources. They were the first class of glycosyltransferases identified in which a single polypeptide species catalyzes the transfer of two different monosaccharides; this finding is in contrast to the usual 'single enzyme, single sugar' dogma of glycobiology. There appear to be two distinct classes of HASs based on differences in amino acid sequence, topology in the membrane, and reaction mechanism. This review discusses the current state of knowledge surrounding the molecular details of HA biosynthesis and summarizes the possible evolutionary history of the HASs. PMID- 11212315 TI - Intrathalamic sensory connections mediated by the thalamic reticular nucleus. AB - The thalamus and cerebral cortex are linked together to form a vast network of interconnections. Different modes of interactions among the cells in this network underlie different states of consciousness, such as wakefulness and sleep. Interposed between the dorsal thalamus and cortex are the GABAergic neurons of the thalamic reticular nucleus (TRN), which play a pivotal role not only in switching between the awake and sleep states but also in sensory processing during the awake state. The visual, somatosensory, and auditory sectors of TRN share many of the same organizational features. Each of these sectors contains maps, which are related to its inputs and outputs, and organizational components called 'slabs.' It is proposed that, during wakefulness, TRN is crucially involved in resetting the activity levels in sensory nuclei of the dorsal thalamus, which allows the cortex to actively and periodically compare its ongoing sensory processing with the available sensory information. PMID- 11212316 TI - Polymorphism in the regulatory sequence of the human hsp70-1 gene does not affect heat shock factor binding or heat shock protein synthesis. AB - A bi-allelic polymorphism found in the regulatory region of the human heat shock (HS) protein (HSP) hsp70-1 gene, which comprises an A-->C transversion, 3 bp upstream of the HS element (HSE), has been associated with extended HLA haplotypes. In view of the chaperoning and protective functions of Hsp70, we investigated whether this hsp70-1 bi-allelic polymorphism could modulate the stress response, which may relate to enhanced resistance or susceptibility to certain diseases. We compared the basal and HS-induced HS factor (HSF)-binding activity of the two polymorphic HSEs, hsp70-1 mRNA accumulation and HSP expression in two human Epstein Barr virus (EBV)-transformed B cell lines typed for hsp70-1 promoter alleles. Our results suggest that hsp70-1 promoter polymorphism does not influence HSF-binding activity, hsp70 mRNA accumulation or synthesis in human EBV-transformed B cell lines. PMID- 11212317 TI - A C-terminally elongated form of PHI from porcine intestine. AB - A C-terminally elongated form of peptide histidine isoleucine amide (PHI) was isolated from porcine intestine based on its effect on cAMP production in IMR-32 cells. The structure was determined by amino acid sequence analysis of tryptic fragments and by mass spectrometry. The peptide has 42 amino acid residues like those described from human, rat and mouse, but the amino acid sequence of the C terminal extension of pig PHI is unique. Unlike the other peptides, it has a C terminal Ala and it differs at five positions from the human form and at six positions from the rat form, while the human and the rat forms differ by only two substitutions. To avoid confusion arising from different C-terminal residues, a unifying nomenclature is proposed: PHI-27 for the hormone and PHI-42 for the elongated product. PMID- 11212318 TI - Xenoreactive natural antibodies. AB - Shortages of human organs for transplantation have made it necessary to examine the possibility of using nonhuman organs for xenotransplantation the transplantation of tissues between different species. Pigs are now regarded as the most likely species to serve as donors for clinical xenotransplantation. However, rejection of pig tissues and organs, mediated by the host's immune system, remains a major barrier to successful xenotransplantation. The primary immunological hurdle to overcome is rejection mediated by antibodies in the host that recognize antigens present on xenogeneic tissues. Since these antibodies are produced naturally in the host without immunization, they are termed natural antibodies. Here, we review the nature of xenoreactive natural antibodies directed toward pig tissues, and summarize recent progress in the field of xenotransplantation directed at overcoming humoral rejection of porcine xenografts. PMID- 11212319 TI - Beyond blood pressure: new roles for angiotensin II. AB - Since the discovery 100 years ago by Tigerstedt and Bergman of renin, an acid protease generating angiotensin peptide, numerous discoveries have advanced our understanding of the renin-angiotensin system (RAS). The recent cloning of angiotensin receptors and the availability of specific receptor ligands have allowed characterization of angiotensin-receptor-mediated actions, and an increasing number of studies using biochemical, pharmacological and molecular biological methods has focused on the many different physiological actions of the RAS in various tissues. Angiotensin II, the main effector peptide of the RAS, exerts most of its known actions in blood pressure control and body fluid homeostasis via the AT, receptor. AT, receptors not only play a role in growth control and cell differentiation but have been implicated in apoptosis and tissue regeneration. This review focuses on the extrarenal functions of angiotensin, especially in neuronal cells and the nervous system, and on recent advances in angiotensin receptor research. PMID- 11212321 TI - The role of adapter proteins in T cell activation. AB - Engagement of antigen receptors on lymphocytes leads to a myriad of complex signal transduction cascades. Recently, work from several laboratories has led to the identification and characterization of novel adapter molecules, proteins with no intrinsic enzymatic activity but which integrate signal transduction pathways by mediating protein-protein interactions. Interestingly, it appears that many of these adapter proteins play as critical a role as the effector enzymes themselves in both lymphocyte development and activation. This review describes some of the biochemical and molecular features of several of these newly identified hematopoietic cell-specific adapter molecules highlighting their importance in regulating (both positively and negatively) signal transduction mediated by the T cell antigen receptor. PMID- 11212320 TI - Are elicitins cryptograms in plant-Oomycete communications? AB - Stimulation of plant natural defenses is an important challenge in phytoprotection prospects. In that context, elicitins, which are small proteins secreted by Phytophthora and Pythium species, have been shown to induce a hypersensitive-like reaction in tobacco plants. Moreover, these plants become resistant to their pathogens, and thus this interaction constitutes an excellent model to investigate the signaling pathways leading to plant resistance. However, most plants are not reactive to elicitins, although they possess the functional signaling pathways involved in tobacco responses to elicitin. The understanding of factors involved in this reactivity is needed to develop agronomic applications. In this review, it is proposed that elicitins could interact with regulating cell wall proteins before they reach the plasma membrane. Consequently, the plant reactivity or nonreactivity status could result from the equilibrium reached during this interaction. The possibility of overexpressing the elicitins directly from genomic DNA in Pichia pastoris allows site-directed mutagenesis experiments and structure/function studies. The recent discovery of the sterol carrier activity of elicitins brings a new insight on their molecular activity. This constitutes a crucial property, since the formation of a sterol elicitin complex is required to trigger the biological responses of tobacco cells and plants. Only the elicitins loaded with a sterol are able to bind to their plasmalemma receptor, which is assumed to be an allosteric calcium channel. Moreover, Phytophthora and Pythium do not synthesize the sterols required for their growth and their fructification, and elicitins may act as shuttles trapping the sterols from the host plants. Sequence analysis of elicitin genes from several Phytophthora species sheds unexpected light on the phylogenetic relationships among the genus, and suggests that the expression of elicitins is under tight regulatory control. Finally, general involvement of these lipid transfer proteins in the biology of Pythiaceae, and in plant defense responses, is discussed. A possible scheme for the coevolution between Phytophthora and tobacco plants is approached. PMID- 11212322 TI - Permeability of rat heart myocytes to cytochrome c. AB - Rat heart myocytes undergoing progressive damage demonstrate morphological changes of shortening and swelling followed by the formation of intracellular vacuoles and plasma membrane blebbing. The damaged myocytes displayed impaired N,N'-tetramethyl-p-phenyldiamine (TMPD) ascorbate-stimulated respiratory activity which was restored by the addition of reduced cytochrome c to the cell culture medium. To clarify the role played by cytochrome c in the impairment of cell respiration, polarographic, spectrophotometric and fluorescence as well as electron microscopy imaging experiments were performed. TMPD/ascorbate-stimulated respiratory activity returned to control levels, at approximately 20 microM cytochrome c, establishing the threshold below which the turnover rate by cytochrome c oxidase in the cell depends on cytochrome concentration. Mildly damaged cardiac myocytes, as indicated by cell shortening, retention of visible striations and free-fluorescein exclusion, together with the absence of lactate dehydrogenase leakage and exclusion of trypan blue, were able to oxidize exogenous cytochrome c and were permeable to fluorescein-conjugated cytochrome c. The results, while consistent with an early cytochrome c release observed at the beginning of cell death, elucidate the role played by cytochrome c in the kinetic control of mitochondrial electron transfer under pathological conditions, particularly those involving the terminal part of the respiratory chain. These data are the first to demonstrate that the sarcolemma of cardiac myocytes, damaged but still viable, is permeable to cytochrome c. PMID- 11212323 TI - Whatever happened to SRY? AB - The mammalian sex-determining gene, SRY, was identified by positional cloning approximately 10 years ago. Since its discovery, intense research into this gene has been directed on two main fronts: elucidation of its function in development of the testis and examination of its singular evolutionary history. The role or SRY as the testis-determining factor (TDF) places it at a crucial point in the highly conserved morphogenetic process of vertebrate gonadogenesis. None of the genes that directly activate SRY nor any of its immediate downstream targets have yet been positively identified. Several genes, however, such as SF1, DAX1, and SOX9, whose spatial and temporal expression profiles overlap with that of SRY, are strongly implicated as co-regulators of gonadogenesis. Molecular genetic manipulation of these genes in mice has shown that they are indispensable to sexual development. Remarkably, its key position in this cascade of gene action has not protected SRY from strong yet poorly understood selective forces that have caused it to evolve rapidly in mammals. The evolution of SRY has been characterized not only by rapid sequence divergence within mammals, but also by structural changes such as intron insertion, gene amplification, and deletion. PMID- 11212324 TI - Cathepsin A/protective protein: an unusual lysosomal multifunctional protein. AB - Cathepsin A/protective protein [3.4.16.5], carboxypeptidase A, is a lysosomal serine protease with structural homology to yeast (Saccharomyces cerevisiae) carboxypeptidase Y. Cathepsin A is a member of the alpha/beta hydrolase fold family and has been suggested to share a common ancestral relationship with other alpha/beta hydrolase fold enzymes, such as cholinesterases. Several lines of evidence indicate that cathepsin A is a multicatalytic enzyme with deamidase and esterase in addition to carboxypeptidase activities. Cathepsin A was recently identified in human platelets as deamidase. In vitro, it hydrolyzes a variety of bioactive peptide hormones including tachykinins, suggesting that extralysosomal cathepsin A plays a role in regulation of bioactive peptide functions. Recent reports emphasize the lysosomal protective function of cathepsin A rather than its protease function. The protective function of cathepsin A is distinct from its catalytic function. Human lysosomal beta-galactosidase and neuraminidase exist as a high molecular weight enzyme complex, in which there is a 54-kDa glycoprotein termed 'lysosomal protective protein'. Based on cell culture studies, protective protein was found to protect both beta-galactosidase and neuraminidase from intralysosomal proteolysis by forming a multienzyme complex and was shown to be deficient in patients with galactosialidosis, a combined deficiency of beta-galactosidase and neuraminidase. Molecular cloning and gene expression studies have disclosed that protective protein is cathepsin A. The cathepsin A precursor has the potential to restore both beta-galactosidase and neuraminidase activities in fibroblasts from patients with galactosialidosis. Cathepsin A knockout mice showed a phenotype similar to human galactosialidosis and the deficient phenotype found in the mutant mice was corrected by transplanting erythroid precursor cells overexpressing cathepsin A. Collectively, these findings demonstrate the significance of cathepsin A as a key molecule in the onset of galactosialidosis and also highlight the therapeutic potential of the cathepsin A precursor for patients with galactosialidosis. PMID- 11212325 TI - Proteasomes in apoptosis: villains or guardians? AB - The proteasome (multicatalytic proteinase complex, prosome) is a major cytoplasmic proteolytic enzyme, responsible for degradation of the vast majority of intracellular proteins. Proteins degraded by the proteasome are usually tagged with multiple ubiquitin moieties, conjugated to the substrates by a complicated cascade of enzymes. Over the last years, evidence has accumulated that changes in the expression and activity of the different components of the ubiquitin proteasome system occur during apoptosis. Proteasome inhibitors have been used to induce apoptosis in various cell types, whereas in others, these compounds were able to prevent apoptosis induced by different stimuli. The proteasome mediated step(s) in apoptosis is located upstream of mitochondrial changes and caspase activation, and can involve in different systems Bcl-2, Jun N-terminal kinase, heat shock proteins, Myc, p53, polyamines and other factors. PMID- 11212326 TI - Plant mitochondrial carriers: an overview. AB - In the two last decades, biochemical studies using mitochondrial swelling experiments or direct solute uptake in isolated mitochondria have lead to the identification of different transport systems at the level of the plant mitochondrial inner membrane. Although most of them have been found to have similar features to those identified in animal mitochondria, some differences have been observed between plant and animal transporters. More recently, molecular biology studies have revealed that most of the mitochondrial exchanges are performed by nuclear encoded proteins, which form a superfamily. Members of this family have been reported in animals, yeast as well as plants. This review attempts to give an overview of the present knowledge concerning the biochemical and molecular characterisation of plant members of the mitochondrial carrier family and, when possible, a comparison with carriers from other organisms. PMID- 11212327 TI - Signalling via caveolin: involvement in the cross-talk between phosphoinositolglycans and insulin. AB - In recent years, a number of cross-talk systems have been identified which feed into the insulin signalling cascade at the level of insulin receptor substrate (IRS) tyrosine phosphorylation, e.g., receptor and non-receptor tyrosine kinases and G-protein-coupled receptors. At the molecular level, a number of negative modulator and feedback systems somehow interacting with the beta-subunit (catecholamine-, phorbolester-, or tumor necrosis factor-alpha-induced serine/threonine phosphorylation, carboxy-terminal trimming by a thiol-dependent protease, association of inhibitory/regulatory proteins such as RAD, PC1, PED, alpha2-HS-glycoprotein) have been identified as candidate mechanisms for the impairment of insulin receptor function by elevations in the activity and/or amount of the corresponding modification enzymes/inhibitors. Both decreased responsiveness and sensitivity of the insulin receptor beta-subunit for insulin induced tyrosine autophosphorylation have been demonstrated in several cellular and animal models of metabolic insulin resistance as well as in the adipose tissue and skeletal muscle of diabetic patients and obese Pima Indians compared to non-obese subjects. Therefore, induction of the insulin signalling cascade by bypassing the defective insulin receptor kinase may be useful for the therapy of non-insulin dependent diabetes mellitus. During the past two decades, phosphoinositolglycans (PIGs) of various origin have been demonstrated to exert potent insulin-mimetic metabolic effects upon incubation with cultured or isolated muscle and adipose cells. However, it remained to be elucidated whether these compounds actually manage to trigger insulin signalling and if so at which level of hierarchy within the signalling cascade the site of interference is located. Recent studies using isolated rat adipocytes and chemically synthesized PIG compounds point to IRS1/3 tyrosine phosphorylation by p59Lyn kinase as the site of cross-talk, the negative regulation of which by interaction with caveolin is apparently abrogated by PIG. This putative mechanism is thus compatible with the recently formulated caveolin signalling hypothesis, the supporting data for which are reviewed here. Though we have not obtained experimental evidence for the involvement of PIG in physiological insulin action, the potential cross-talk between insulin and PIG signalling, including the caveolae/detergent-insoluble glycolipid-enriched rafts as the compartments where the corresponding signalling components are concentrated, thus represent novel targets for signal transduction therapy. PMID- 11212328 TI - Pathophysiology of mitochondrial cell death control. AB - Mitochondria have been recently recognized to play a major role in the control of apoptosis or programmed cell death. Permeabilization of mitochondrial membranes, a decisive feature of early cell death, is regulated by members of the Bcl-2 family which interact with the permeability transition pore complex (PTPC). Thus, the cytoprotective oncoprotein Bcl-2 stabilizes the mitochondrial membrane barrier function, whereas the tumor suppressor protein Bax permeabilizes mitochondrial membranes. The regulation of membrane permeabilization is intertwined with that of the bioenergetic and redox functions of mitochondria. The implications of alterations in the composition of the PTPC and in mitochondrial function for the pathophysiology of cancer (reduced apoptosis) and neurodegeneration (enhanced apoptosis) are discussed. PMID- 11212329 TI - Insights from von Willebrand disease animal models. AB - von Willebrand disease is a genetic bleeding disorder that arises from abnormalities in von Willebrand factor, an adhesive glycoprotein involved in both primary hemostasis and coagulation. It is the most common inherited bleeding disorder in humans, and over the years several animal species have also been described as suffering from this disease whether through a spontaneous mutation (pigs, dogs) or a genetically engineered one (mouse). These different animal models are extremely useful in exploring the characteristics of von Willebrand disease and in testing new treatments. This review provides an update of the various von Willebrand disease models and the contribution that these models can make to a better understanding of human von Willebrand disease. PMID- 11212330 TI - The active role of astrocytes in synaptic transmission. AB - In the central nervous system, astrocytes form an intimately connected network with neurons, and their processes closely enwrap synapses. The critical role of these cells in metabolic and trophic support to neurons, ion buffering and clearance of neurotransmitters is well established. However, recent accumulating evidence suggests that astrocytes are active partners of neurons in additional and more complex functions. In particular, astrocytes express a repertoire of neurotransmitter receptors mirroring that of neighbouring synapses. Such receptors are stimulated during synaptic activity and start calcium signalling into the astrocyte network. Intracellular oscillations and intercellular calcium waves represent the astrocyte's own form of excitability, as they trigger release of transmitter (i.e. glutamate) via a novel process sensitive to blockers of exocytosis and involving cyclooxygenase eicosanoids. Astrocyte-released glutamate activates receptors on the surrounding neurons and modifies their electrical and intracellular calcium ([Ca2+]i) state. These exciting new findings reveal an active participation of astrocytes in synaptic transmission and the involvement of neuronastrocyte circuits in the processing of information in the brain. PMID- 11212331 TI - Evolution of bacterial pathogenesis. AB - The evolution of bacteria is associated with continuous generation of novel genetic variants. The major driving forces in this process are point mutations, genetic rearrangements, and horizontal gene transfer. A large number of human and animal bacterial pathogens have evolved the capacity to produce virulence factors that are directly involved in infection and disease. Additionally, many bacteria express resistance traits against antibiotics. Both virulence factors and resistance determinants are subject to intrastrain genetic and phenotypic variation. They are often encoded on unstable DNA regions. Thus, they can be readily transferred to bacteria of the same species or even to non-related prokaryotes. This review article focuses on the main mechanisms of bacterial microevolution responsible for the rapid emergence of variants with novel virulence and resistance properties. In addition, processes of macroevolution are described with special emphasis on gene transfer and fixation of adaptive mutations in the genome of pathogens. PMID- 11212332 TI - Short sequence repeats in microbial pathogenesis and evolution. AB - Repetitive DNA is ubiquitous in microbial genomes. Different classes of short sequence repeats (SSRs) have been identified and demonstrated to be generally heterogeneous in a locus-dependent manner, reflected in variation in the number of repeat units present at a given genomic site or by sequence heterogeneity among individual units. Both types of variability can be used to assess intra species genetic diversity. Repeat variability often affects the coding potential of the region in which the repetitive element is located. This implies that determination of the primary structure of variable numbers of tandem repeats can be used for epidemiological identification purposes, and also for the analysis of gene function. Precise assessment of SSR structure can also generate insight into the regulation of gene expression. Together, DNA repeat analysis in microbial species provides information on both functional and evolutionary aspects of genetic diversity among microbial isolates. PMID- 11212333 TI - Evolution of virulence factors in Shiga-toxin-producing Escherichia coli. AB - The major demonstrated or putative virulence factors of Shiga-toxin-producing Escherichia coli (STEC) are the Shiga toxins, products of the locus of enterocyte effacement, and products encoded by the EHEC-hemolysin plasmid. Molecular analysis shows that STEC acquired the majority of these virulence factors by horizontal transfer of genetic material. In the case of Shiga toxins, the phages encoding them are probably responsible for this transfer. For the locus of enterocyte effacement, however, it is not clear how often this transfer took place and which parts of the locus were involved in this transfer. The large EHEC hemolysin plasmid is clearly a mosaic structure, which arose from multiple recombination events with foreign DNA. Two lineages of this plasmid can be distinguished, one of which is associated with chromosomally encoded virulence factors. Despite the wealth of information available, further comparative studies are needed to decipher definitively the evolution of virulence in STEC. PMID- 11212334 TI - Antibiotic resistance in microbes. AB - The treatment of infectious disease is compromised by the development of antibiotic-resistant strains of microbial pathogens. A variety of biochemical processes are involved that may keep antibiotics out of the cell, alter the target of the drug, or disable the antibiotic. Studies have shown that resistance determinants arise by either of two genetic mechanisms: mutation and acquisition. Antibiotic resistance genes can be disseminated among bacterial populations by several processes, but principally by conjugation. Thus the overall problem of antibiotic resistance is one of genetic ecology and a better understanding of the contributing parameters is necessary to devise rational approaches to reduce the development and spread of antibiotic resistance and so avoid a critical situation in therapy--a return to a pre-antibiotic era. PMID- 11212335 TI - Spread of antibiotic resistance with food-borne pathogens. AB - This short review summarizes data on antibiotic resistance profiles of common food-borne pathogens like Salmonella sp., Escherichia coli, Campylobacter sp., Listeria monocytogenes, Clostridium perfringens, Staphylococcus aureus, and coagulase-negative staphylococci. As a flashlight on the literature of the last few years, it provides ample evidence that antibiotic resistance traits have entered the microflora of farm animals and the food produced from them. Molecular analysis of the resistance genes, where available, shows that the food microflora is not separated from its human counterpart and conjugative transfer of resistance genes has been demonstrated in vitro and in a few cases in vivo. For example, for Salmonella typhimurium, resistance towards tetracyclines has increased from zero in 1948 to a 98% level in certain epidemic populations of S. typhimurium DT104 in 1998. The high incidence of food-borne pathogens in raw meat and milk together with a high level of therapeutic, prophylactic and nutritional application of antibiotics in agriculture reveals an antibiotic resistance problem of global dimensions. The resistance problem in human medicine will not be solved if there is a constant influx of resistance genes into the human microflora via the food chain. PMID- 11212336 TI - Genetic basis of methicillin resistance in Staphylococcus aureus. AB - Methicillin resistance in staphylococci is due to the acquisition of the mecA gene encoding a new penicillin-binding protein (PBP2', PBP2a) that has a lower affinity to methicillin than the endogenous PBPs. PBP2' is involved in the assembly of the cell wall peptidoglycan in the presence of high concentrations of beta-lactams that otherwise inhibit the endogenous PBPs. The production of PBP2' is under dual control by its own mecR1-mecI- and the penicillinase blaR1-blaI encoded regulatory elements. Resistance to high levels of methicillin depends, in addition to PBP2', on chromosomally encoded factors that are involved in the synthesis and degradation of the peptidoglycan. Any mutations that reduce peptidoglycan precursor formation or change the chemical composition of the muropeptide precursor result in lowered resistance. PMID- 11212337 TI - Bacterial antibiotic efflux systems of medical importance. AB - Multidrug efflux systems endow on bacterial cells the ability to limit the access of antimicrobial agents to their targets. By actively pumping out antibiotic molecules, these systems prevent the intracellular accumulation necessary for antibiotics to exert their lethal activity. Drug efflux appears to be one of the most widespread antibiotic resistance mechanisms among microorganisms, since it has been demonstrated to occur in many Gram-positive and Gram-negative bacteria including medically important species like staphylococci, streptococci, enterobacteria and opportunistic pathogens like Pseudomonas aeruginosa. Efflux pumps can be specific for only one substrate or accommodate a more or less wide range of noxious products. Export of structurally unrelated compounds confers a multidrug-resistance phenotype on bacterial cells. Therapeutically critical levels of resistance can be achieved by overexpression of efflux systems, especially in those species such as P. aeruginosa which possess a low outer membrane permeability. It is suspected that the dual physiological function of active efflux systems is both the secretion of intracellular metabolites and the protection against a variety of harmful substances that the microorganism may encounter in its natural environment. PMID- 11212338 TI - Bacterial targets and antibiotics: genome-based drug discovery. AB - The requirement for novel classes of antibiotics to combat the emergence of resistant and multi-resistant bacteria has coincided with the completion sequencing of a number of bacterial genomes. The in silico analysis of these genomes coupled with innovative genetic manipulation has already led to the identification of conserved essential (either in vitro or in vivo, depending on the methodology) genes that are potential targets for antibacterial research. New technologies, made possible by access to the genomic sequences, are capable of simultaneously quantifying almost the entire complement of gene products synthesised by bacterial cells. These technologies are opening up the way for the analysis of expression patterns elicited in cells in response to changes in their environment. The integration of these technologies into the drug discovery process is still in its infancy and the potential wealth of information, some of it already available, has yet to be fully realised. PMID- 11212339 TI - Phosphorylation-dependent prolyl isomerization: a novel signaling regulatory mechanism. AB - Protein phosphorylation on serine or threonine residues preceding proline (Ser/Thr-Pro) plays an essential role for regulating various cellular processes, including cell cycle progression. Although phosphorylation has been proposed to regulate the function of a protein by inducing conformational changes, much less is known about what phosphate additions actually do and how the functions of phosphoproteins are coordinated. Proline is important for determining protein structure because it exists in cis or trans conformation and can put kinks into a polypeptide chain. We have shown that phosphorylation on Ser/Thr-Pro motifs reduces the cis/trans isomerization rate of Ser/Thr-Pro bonds. At the same time, proteins containing phosphorylated Ser/Thr-Pro motifs are substrates for the prolyl isomerase Pin1. The WW domain of Pin1 acts as a phosphoserine/threonine binding module binding a defined subset of mitosis-specific phosphoproteins, such as Cdc25 and tau. These interactions target the enzymatic activity of Pin1 close to its substrates. In contrast to other prolyl isomerases (peptidyl-prolyl isomerases, PPlases), Pin1 has an extremely high degree of substrate specificity, specifically isomerizing phosphorylated Ser/Thr-Pro bonds. Therefore, Pin1 binds and regulates the function of a defined subset of phosphoproteins. Furthermore, inhibiting Pin1 function is lethal for dividing cells. Interestingly, Pin1, which can restore the biological function of phosphorylated tau, is sequestered in the neurofibrillary tangles in Alzheimer's brains. Thus, we have proposed a novel signaling regulatory mechanism, where protein phosphorylation creates binding sites for Pin1, which can then latch on to and isomerize the phosphorylated Ser/Thr-Pro peptide bond. In turn, this may change the shape of the protein, regulating its activity, dephosphorylation, degradation or location in the cell. This new post-phosphorylation regulatory mechanism appears to play an important role in normal cell function, such as mitotic progression, and in the pathogenesis of some human pathologies, such as Alzheimer's disease. PMID- 11212340 TI - Yeast aging research: recent advances and medical relevance. AB - The molecular mechanisms of aging are most fully understood for the budding yeast Saccharomyces cerevisiae. Recent advances in our understanding of aging in this organism have enabled researchers to answer some fundamental questions about the aging process. Is aging due to a multitude of 'mechanisms' or can there be a key few? Can we design single-gene mutations that will prolong life? Can we prolong life whilst maintaining health and fecundity? The various contributing factors to yeast longevity, uncovered thus far, fall into three classes: DNA metabolism, heterochromatin, and metabolic activity. However, these separate classes may actually represent different aspects of the same aging mechanism based on genome stability. This review examines the recent advances in our understanding of yeast aging and discusses their relevance, if any, to the human condition. PMID- 11212341 TI - The preprotein translocase of the outer mitochondrial membrane: receptors and a general import pore. AB - Cytosol-synthesized preproteins destined for the mitochondria are transported across the outer membrane by the translocase of the mitochondrial outer membrane (TOM complex). This dynamic transport machinery can be divided into receptors that recognize preprotein targeting signals and components of the general import pore complex that mediate preprotein transport across the outer membrane. This review focuses on recent studies dealing with the central questions regarding the pore-forming subunits, and architecture and gating of the translocation channel of the outer membrane. PMID- 11212342 TI - ATP-dependent proteases controlling mitochondrial function in the yeast Saccharomyces cerevisiae. AB - Regulated protein degradation by ATP-dependent proteases plays a fundamental role in the biogenesis of mitochondria. Membrane-bound and soluble ATP-dependent proteases have been identified in various subcompartments of this organelle. Subunits composing these proteases are evolutionarily conserved from yeast to humans and, in support of an endosymbiotic origin of mitochondria, evolved from prokaryotic ancestors: the PIM1/Lon protease is active in the matrix of mitochondria, while the i-AAA protease and the m-AAA protease mediate the turnover of inner membrane proteins. Most of the knowledge concerning the biogenesis and the physiological role of ATP-dependent proteases comes from studies in the yeast Saccharomyces cerevisiae. Proteases were found to be required for mitochondrial stasis, for the maintenance of the morphology of the organelle and for mitochondrial genome integrity. ATP-dependent proteolysis is crucial for the expression of mitochondrially encoded subunits of respiratory chain complexes and for the assembly of these complexes. Hence, mitochondrial ATP dependent proteases exert multiple roles which are essential for the maintenance of cellular respiratory competence. PMID- 11212343 TI - Glycine: a new anti-inflammatory immunonutrient. AB - The mechanism of the immunosuppressive effects of glycine and its pathophysiological applications are discussed in this review. Glycine has been well characterized in spinal cord as an inhibitory neurotransmitter which activates a glycine-gated chloride channel (GlyR) expressed in postsynaptic membranes. Activation of the channel allows the influx of chloride, preventing depolarization of the plasma membrane and the potentiation of excitatory signals along the axon. Glycine has recently been shown to have similar inhibitory effects on several white blood cells, including hepatic and alveolar macrophages, neutrophils, and lymphocytes. Pharmacological analysis using a GlyR antagonist strychnine, chloride-free buffer, and radiolabeled chloride has provided convincing evidence to support the hypothesis that many white blood cells contain a glycine-gated chloride channel with properties similar to the spinal cord GlyR. Molecular analysis using reverse transcription-polymerase chain reaction and Western blotting has identified the mRNA and protein for the beta subunit of the GlyR in total RNA and purified membrane protein from rat Kupffer cells. Dietary glycine is protective in rat models against endotoxemia, liver ischemia reperfusion, and liver transplantation, most likely by inactivating the Kupffer cell via this newly identified glycine-gated chloride channel. Glycine also prevents the growth of B 16 melanomas cell in vivo. Moreover, dietary glycine is protective in the kidney against cyclosporin A toxicity and ischemia-reperfusion injury. Glycine may be useful clinically for the treatment of sepsis, adult respiratory distress syndrome, arthritis, and other diseases with an inflammatory component. PMID- 11212344 TI - Cell surface heparan sulfate proteoglycans and lipoprotein metabolism. AB - Cell surface heparan sulfate proteoglycans are involved in several aspects of the lipoprotein metabolism. Most of the biological activities of these proteoglycans are mediated via interactions of their heparan sulfate moieties with various protein ligands, including lipoproteins and lipases. The binding of lipoproteins to heparan sulfate is largely determined by their apoprotein composition, and apoproteins B and E display the highest affinity for heparan sulfate. Interactions of lipoproteins with heparan sulfate are important for the cellular uptake and turnover of lipoproteins, in part by enhancing the accessibility of lipoproteins to lipoprotein receptors and lipases. Apoprotein B may interact with receptors without involving heparan sulfate. Heparan sulfate has been further implicated in presentation and stabilization of lipoprotein lipase and hepatic lipase on cell surfaces and in the transport of lipoprotein lipase from extravascular cells to the luminal surface of the endothelia. In atherosclerosis, heparan sulfate is intimately involved in several events important to the pathophysiology of the disease. Heparan sulfate thus binds and regulates the activity of growth factors, cytokines, superoxide dismutase and antithrombin, which contribute to aberrant cell proliferation, migration and matrix production, scavenging of reactive oxygen radicals and thrombosis. In this review we discuss the various roles of heparan sulfate proteoglycans in vascular biology, with emphasis on interactions of heparan sulfate with lipoproteins and lipases and the molecular basis of such interactions. PMID- 11212345 TI - The rat beta (b miny)-globin promoter: nuclear protein factors and erythroid specific induction of transcription. AB - We show that the rat adult beta (b miny)-globin gene is transcriptionally active. The - 100-bp promoter region contains control elements that are important for the induction of transcription in rat erythroleukemia (REL) cells. By using DNaseI footprinting and gel mobility shift assays, we have shown that the CCAAT box, a regulatory element from an analyzed promoter region, binds NF-Y and GATA-1 transcription factors. Another regulatory element from this region, betaDRE, binds erythroid-specific and ubiquitous factors from REL cells. Although both the CCAAT box region and betaDRE element bind the same protein factors before and after induction of REL cells, we show by South-Western blot analysis that the concentrations of 150-kDa, 70-kDa and 60-kDa factors binding to the betaDRE are increased in DMSO-induced REL cells. PMID- 11212346 TI - The diversity of molecular motors: an overview. AB - Rapid progress has recently been made in the identification and characterization of a large number of kinesin and myosin motor proteins. Recent work has uncovered roles for these motors in processes such as vesicle trafficking, cytoskeletal organization, and chromosome movements, to name a few. A series of reviews describing some of the significant advances in our understanding of the structure and function of myosins and kinesins is presented. PMID- 11212347 TI - Three-dimensional structure of motor molecules. AB - Images, calculated from electron micrographs, show the three-dimensional structures of microtubules and tubulin sheets decorated stoichiometrically with motor protein molecules. Dimeric motor domains (heads) of kinesin and ncd, the kinesin-related protein that moves in the reverse direction, each appeared to bind to tubulin in the same way, by one of their two heads. The second heads show an interesting difference in position that seems to be related to the directions of movement of the two motors. X-ray crystallographic results showing the structures of kinesin and ncd to be very similar at atomic resolution, and homologous also to myosin, suggest that the two motor families may use mechanisms that have much in common. Nevertheless, myosins and kinesins differ kinetically. Also, whereas conformational changes in the myosin catalytic domain are amplified by a long lever arm that connects it to the stalk domain, kinesin and ncd do not appear to possess a structure with a similar function but may rely on biased diffusion in order to move along microtubules. PMID- 11212348 TI - Kinesins in the nervous system. AB - Both the development and the maintenance of neurons require a great deal of active cytoplasmic transport. Much of this transport is driven by microtubule motor proteins. Membranous organelles and other macromolecular assemblies bind motor proteins that then use cycles of adenosine 5'-triphosphate hydrolysis to move these 'cargoes' along microtubules. Different sets of cargoes are transported to distinct locations in the cell. The resulting differential distribution of materials almost certainly plays an important part in generating polarized neuronal morphologies and in maintaining their vectorial signalling activities. A number of different microtubule motor proteins function in neurons; presumably they are specialized for accomplishing different transport tasks. Questions about specific motor functions and the functional relationships between different motors present a great challenge. The answers will provide a much deeper understanding of fundamental transport mechanisms, as well as how these mechanisms are used to generate and sustain cellular asymmetries. PMID- 11212349 TI - Kinesin-II, the heteromeric kinesin. AB - The kinesins constitute a large family of motor proteins which are responsible for the distribution of numerous organelles, vesicles and macromolecular complexes throughout the cell. One class of these molecular motors, kinesin-II, is unique in that these proteins are typically found as heterotrimeric complexes containing two different, though related, kinesin-like motor subunits, and a single nonmotor subunit. The heteromeric nature of these kinesins appears to have resulted in a class of combinatorial kinesins which can 'mix and match' different motor subunits. Another novel feature of these motors is that the activities of several kinesin-II representatives are essential in the assembly of motile and nonmotile cilia, a role not attributed to any other kinesin. This review presents a brief overview of the structure and biological functions of kinesin-II, the heteromeric kinesin. PMID- 11212350 TI - Myosins from plants. AB - Molecular cloning and sequence analysis of myosin genes from Arabidopsis thaliana and electron microscopic observation of a myosin from characean alga have revealed that overall structure of plant unconventional myosins is similar to that of the class V myosins. These plant unconventional myosins have two heads, a coiled-coil tail of varied length and a globular tail piece at the end. The tail piece is probably a site for membrane interaction. Characean myosin is of special interest because it can translocate actin filaments at a velocity several times faster than muscle myosin, which must have evolved to support the quick movement of animals in the struggle for their lives. PMID- 11212351 TI - Myosin-V: head to tail. AB - The myosin-V family is the most extensively studied of the unconventional myosin families. Most organisms examined have at least one member of the myosin-V family: many have multiple members. The wide range of species in which myosin-V has been identified suggests that myosin-V is a fundamental component of organelle transport in all higher eukaryotes. Possible cargoes for myosin-V range from melanosomes and synaptic vesicles in mammals to vacuoles and messenger RNA in yeast. In this review, we discuss the current state of research on the cellular function of myosin-V as described by the actions of the head, neck and tail domains. PMID- 11212352 TI - Tails of unconventional myosins. AB - In addition to the conventional myosins (class II) required for processes such as muscle contraction and cytokinesis, the myosin superfamily of actin-based motor proteins includes at least 14 'unconventional' classes. These unconventional myosins are defined by myosin-like head (motor) domains attached to class specific tail domains that differ greatly from those of myosin-II. The unconventional myosins account for almost two-thirds of the 28 or more myosin genes currently believed to be expressed in humans and 80-90% of the approximately 10 or more myosin genes expressed in a typical nonmuscle cell. Although these members of the myosin superfamily have not been as intensively investigated as the conventional myosins, unconventional myosins are known or believed to power many forms of actin-based motility and organelle trafficking. The presence of signaling domains such as kinase domains, SH3 domains, PH domains or GTPase-activating domains in the tails of unconventional myosins indicates that these proteins can also be components of signal transduction pathways. Since several classes of the myosin superfamily have been found only in lower eukaryotes or plants (VIII, XI, XIII and XIV), in this review we will focus on the structures and properties of the unconventional myosins found in multicellular animals (excluding classes I and V, which have been reviewed elsewhere recently). Special attention will be focused on the three classes of unconventional myosins that can cause deafness in mouse or humans when mutated. In addition, we discuss the discovery of a pair of intriguing domains, the Myosin Tail Homology 4 (MyTH4) and FERM (band 4.1, Ezrin, Radixin, Moesin) domains, that are present in the tails of otherwise very different myosins as well as a plant kinesin-like protein. Recent progress in the identification of novel unconventional myosins will also be summarized. PMID- 11212353 TI - Molecular genetics of Usher syndrome. AB - The Usher syndrome, an autosomal recessive deafness and blindness, is genetically and clinically heterogeneous. In the past 4 years, genes mutated in Usher syndrome type Ib and type IIa have been described. The Usher Ib gene encodes the motor protein myosin VIIa and was identified as the human homolog of the mouse shaker-1 gene. The Usher type IIa gene was identified by positional cloning and encodes a protein with homology to extracellular matrix proteins and cell adhesion molecules. This review summarizes the current knowledge regarding both the genetic and molecular aspects of Usher syndrome in the context of recent scientific advances in the areas of sensorineural deafness and retinitis pigmentosa. PMID- 11212354 TI - Molecular pathogenesis of apolipoprotein E-mediated amyloidosis in late-onset Alzheimer's disease. AB - Apolipoprotein E (apoE) epsilon4 allele is a genetic risk factor for late-onset familial and sporadic Alzheimer's disease (AD). In the central nervous system, apoE is secreted mainly by astrocytes as a constituent of high-density lipoproteins. A recent study using apoE knockout mice provided strong evidence that apoE promotes cerebral deposition of amyloid beta protein (Abeta). However, no clear explanation of the pathogenesis of apoE-induced AD has been provided. Here we discuss two possible mechanisms by which apoE might enhance Abeta deposition. One is the intracellular pathway in which apoE is internalized by neurons and induces lysosomal accumulation of Abeta and amyloidogenic APP (amyloid precursor protein) fragments, leading to neuronal death. The other is the extracellular pathway in which apoE-containing lipoproteins are trapped by Abeta1-42 deposits mobilizing soluble Abeta peptides and consequently enlarge amyloid plaques. These two mechanisms may operate at different stages of AD pathogenesis and suggest a chaperone-like function for the apoE molecule PMID- 11212355 TI - Oxazolidinones: a novel class of antibiotics. AB - Oxazolidinones are a novel class of synthetic antimicrobial agents which have now entered phase III clinical trials. The most promising feature of these compounds is their oral activity against multidrug-resistant Gram-positive bacteria which have created tremendous therapeutic problems in recent years. In addition, development of resistance in vitro has so far remained below detectable levels. Different from many antibacterial agents used in the treatment of human infections, oxazolidinones do not block bacterial protein synthesis at the level of polypeptide chain elongation but rather seem to interfere with initiation of translation. Both binding of formylmethionine-transfer RNA to initiation complexes as well as release of formylmethioninepuromycin from initiation complexes have been reported to be targets for oxazolidinones. The major binding sites of oxazolidinones are the large (50S) ribosomal subunits. PMID- 11212356 TI - Immunoglobulin-binding proteins in ticks: new target for vaccine development against a blood-feeding parasite. AB - Humans have a long history of trying to control ticks. At first, attempts focused on modifying the habitat, whereas later efforts relied heavily on the use of chemicals. Current research is directed at finding a vaccine against ticks. A strategy of targeting 'concealed antigens' succeeded with the first commercialised vaccine against the cattle tick Boophilus microplus. However, vaccine development against other tick species appears unsatisfactory to date. Vaccination depends on a specific antibody-mediated immunoreaction that damages the parasite. Immunoglobulin molecules of vertebrate hosts can pass through gut barriers into the haemolymph of ectoparasites while retaining antibody activity. Research on the ixodid tick Rhipicephalus appendiculatus revealed that host immunoglobulin-G in the parasite was excreted via salivation, during feeding. Immunoglobulin-binding proteins in tick haemolymph and salivary glands are thought to be responsible for such excretion. The discovery of an immunoglobulin excretion system in ticks indicates that they have a highly developed mechanism to protect themselves from their host's antibody attack. Such a mechanism questions whether immunization strategies will be effective against ticks, unless they circumvent or disable the ticks' immunoglobulin excretion system. PMID- 11212357 TI - Role of the inositol 1,4,5-trisphosphate receptor in early embryonic development. AB - There is now considerable literature on the importance of phosphatidylinositol cycle activation in transducing information of various types across the plasma membrane. Though much of the data derives from studies on somatic cells, there is increasing evidence for crucial events related to development, including fertilization, cell cycle progression and dorsoventral axis formation. In this review, focus is directed mainly to the molecular basis of the inositol 1,4,5 triphosphate receptor expressed in oocytes and early embryos of Xenopus. Recent progress in studies concerning the role of this receptor in early embryonic development is discussed. PMID- 11212358 TI - The pleiotropic functions of aspirin: mechanisms of action. AB - Recent studies have suggested that aspirin and aspirin-like compounds have a variety of actions in addition to their well-studied ability to inhibit cyclooxygenases. These actions include inhibition of the uncoupling of oxidative phosphorylation, decreases in adenosine triphosphate stores. increases in extracellular adenosine, downregulation of the expression and activity of inducible nitric oxide synthetase, inhibition and/or stimulation of various mitogen-activated protein kinase activities and inhibition of nuclear factor binding kappaB site (NF-kappaB) activation. Moreover, aspirin-like compounds have recently been shown to have previously unappreciated clinical and biological effects, some apparently independent of cyclooxygenase. In this review we discuss the various mechanisms of action of aspirin-like compounds and their relevance to clinical disease and therapy. PMID- 11212359 TI - Geminivirus DNA replication. AB - Geminiviruses are DNA viruses which infect plants. They have a small genome and encode only a few proteins. Therefore, their DNA replication cycle relies largely on the use of cellular DNA replication proteins. The strategy used by geminiviruses to replicate their single-stranded DNA (ssDNA) genome consists of a first stage of conversion of ssDNA into double-stranded DNA (dsDNA) intermediates and, then, the use of dsDNA as a template to amplify viral dsDNA and to produce mature ssDNA genomes by a rolling-circle replication mechanism. In addition, the accumulating evidence indicates that viral DNA replication is somehow coupled to the cell cycle regulatory network of the infected cell. For these reasons, geminiviruses are excellent model systems to understand the regulation of DNA replication and cell cycle in plant cells. Recent years have witnessed significant progress in the identification of cis-acting signals and their interaction with trans-acting factors that contribute to geminivirus origin function. These and other aspects of the geminivirus DNA replication cycle will be reviewed. PMID- 11212360 TI - Chlorophyll breakdown in higher plants and algae. AB - Leaf senescence is accompanied by the metabolism of chlorophyll (Chl) to nonfluorescent catabolites (NCCs). The pathway of Chl degradation comprises several reactions and includes the occurrence of intermediary catabolites. After removal of phytol and the central Mg atom from Chl by chlorophyllase and Mg dechelatase, respectively, the porphyrin macrocycle of pheophorbide (Pheide) a is cleaved. This two-step reaction is catalyzed by Pheide a oxygenase and RCC reductase and yields a primary fluorescent catabolite (pFCC). After hydroxylation and additional species-specific modifications, FCCs are tautomerized nonenzymically to NCCs inside the vacuole. Different subcellular compartments participate in Chl catabolism and, thus, transport processes across membranes are required. This review focuses on the catabolites and the individual reactions of Chl breakdown in higher plants. In addition, the pathway is compared to Chl conversion to red catabolites in an alga, Chlorella protothecoides. Finally, the significance and regulation of Chl degradation are discussed. PMID- 11212361 TI - Picroliv modulates the expression of insulin-like growth factor (IGF)-I, IGF-II and IGF-I receptor during hypoxia in rats. AB - The insulin-like growth factors (IGFs), IGF-I and IGF-II, play important roles in normal growth and differentiation. In recent studies, IGFs have been implicated in tissue repair and regeneration after hypoxicischemic injury. The growth effects of these genes are exerted primarily through IGF-I receptor (IGF-IR). We have earlier shown that picroliv, obtained from the roots of Picrorhiza kurrooa, reduces cellular damage caused by hypoxia in vitro. We have now studied the modulation of IGF-I, IGF-II and IGF-IR in hypoxia and the ability of picroliv to modify their expression in vivo. Male Sprague-Dawley rats, placed in 10% oxygen for 4 days, were sacrificed, and the expression of IGF-I, IGF-II and IGF-IR was determined by immunohistochemistry, in situ hybridization and reverse transcriptase polymerase chain reaction (RT-PCR) in brain, liver and lung. One group of animals was pretreated with picroliv and the other served as control. IGF-I and IGF-IR were expressed in distinct regions of the brain but not in liver or lung. IGF-I was mainly expressed in the hippocampus and cerebellum, whereas IGF-IR expression was also observed in the cortex. A significant reduction in the messenger RNA (mRNA) level of these genes was observed in response to hypoxia. Pretreatment with picroliv not only prevented such downregulation but more importantly resulted in increased levels of IGF-I and IGF-IR. These observations correlated with reduced neuronal cell death observed in these animals. The mRNA of IGF-II was constitutively expressed and was not altered by hypoxia. Modulation of IGF-I and IGF-II expression by picroliv, a novel pharmacological agent, could benefit in similar clinical settings such as myocardial ischemia and certain cerebral injuries. PMID- 11212363 TI - In vivo effect of sodium valproate on mouse liver. AB - The in vivo effect of sodium valproate (SV) on the activity of uridine diphosphate glucuronosyltransferase (UDP-GT) and hepatotoxicity in the mouse liver was studied. Mice were injected intraperitoneally (IP) with SV at doses varying from 50 to 800 mg/kg per day, for six consecutive days (dose-response group) or at a standard dose of 300 mg/g per day for 2-10 days (time-response group), whereas the controls were injected with normal saline. Valproic acid levels had a positive correlation to the dose (P < 0.001) and duration of drug administration (P = 0.006). A gradual increase in UDP-GT activity was observed in doses of up to approximately 400 mg/kg per day, whereas in higher doses the enzyme activity gradually decreased. The time course of UDP-GT activity at the standard dose of 300 mg/kg per day increased progressively, with a maximum up to the sixth day and then had a gradual reduction. Hepatic necrosis (which was unrelated to the dose or the duration of drug administration) was found in 13% of the SV-treated animals and in none of the controls. We conclude that at an optimal dose (300-400 mg/kg per day) and at a time course of 6 days, SV causes liver UDP-GT induction, whereas in higher doses and longer duration of administration, UDP-GT activity is gradually reduced. SV also causes hepatotoxicity unrelated to dose and time course. PMID- 11212362 TI - Detection of HLA-E and -G DNA alleles for population and disease studies. AB - HLA-E and -G genes show a restricted polymorphism encoding for molecules whose variability is limited at the peptide binding site. Fourteen alleles that give rise to only three productive proteins for HLA-G (*0101, *0103 and *0104) and five alleles with three different proteins for HLA-E (*0101, *0102 and *0103) have been described. Expression of these molecules is low and found in many tissues for HLA-E: HLA-G protein is expressed in extravillous trophoblast cells and thymic epithelium. Molecular studies have shown how HLA-G and HLA-E bind to natural killer (NK) cells immunoglobulin and lectin-type inhibitory receptors. HLA-E may act as a sentinel of the cell; if classical class I and HLA-G are being expressed, HLA-E molecules may reach the cell surface and inhibit the lysis by NK cells. Most findings are consistent with the hypothesis that HLA-E and -G proteins may be tolerogenic molecules at either the T-cell receptor (TcR) (inflammation, graft rejection) or NK level, switching off cells which usually attack foreign (including foetus) or self (autoimmune) antigens. A low HLA-E and G polymorphism is observed in humans, and their allele frequencies are mostly homogeneous in the populations tested so far. Many studies to detect these alleles are now being performed in isolated populations and also in pregnancy associated pathologies. In the present paper, standard and detailed techniques to detect HLA-E and -G DNA polymorphism are reported and discussed. PMID- 11212364 TI - Reconstruction of MR images from data acquired on a general nonregular grid by pseudoinverse calculation. AB - A minimum-norm least-squares image-reconstruction method for the reconstruction of magnetic resonance images from non-Cartesian sampled data is proposed. The method is based on a general formalism for continuous-to-discrete mapping and pseudoinverse calculation. It does not involve any regridding or interpolation of the data and therefore the methodology differs fundamentally from existing regridding-based methods. Moreover, the method uses a continuous representation of objects in the image domain instead of a discretized representation. Simulations and experiments show the possibilities of the method in both radial and spiral imaging. Simulations revealed that minimum-norm least-squares image reconstruction can result in a drastic decrease of artifacts compared with regridding-based reconstruction. Besides, both in vivo and phantom experiments showed that minimum-norm least-squares image reconstruction leads to contrast improvement and increased signal-to-noise ratio compared with image reconstruction based on regridding. As an appendix, an analytical calculation of the raw data corresponding to the well-known Shepp and Logan software head phantom is presented. PMID- 11212365 TI - Optimal k-space sampling in MRSI for images with a limited region of support. AB - Magnetic resonance spectroscopic imaging requires a great deal of time to gather the data necessary to achieve satisfactory resolution. When the image has a limited region of support (ROS), it is possible to reconstruct the image from a subset of k-space samples. Therefore, we desire to choose the best possible combination of a small number of k-space samples to guarantee the quality of the reconstructed image. Sequential forward selection (SFS) is appealing as an optimization method because the previously selected sample can be observed while the next sample is selected. However, when the number of selected k-space samples is less than the number of unknowns at the beginning of the selection process, the optimality criterion is undefined and the resulting SFS algorithm cannot be used. In this paper, we present a modified form of the criterion that overcomes this problem and develop an SFS algorithm for the new criterion. Then we develop an efficient computational strategy for this algorithm as well as for the standard SFS algorithm. The combined algorithm efficiently selects a reduced set of k-space samples from which the ROS can be reconstructed with minimal noise amplification. PMID- 11212366 TI - Brain tissue classification of magnetic resonance images using partial volume modeling. AB - This paper presents a fully automatic three-dimensional classification of brain tissues for Magnetic Resonance (MR) images. An MR image volume may be composed of a mixture of several tissue types due to partial volume effects. Therefore, we consider that in a brain dataset there are not only the three main types of brain tissue: gray matter, white matter, and cerebro spinal fluid, called pure classes, but also mixtures, called mixclasses. A statistical model of the mixtures is proposed and studied by means of simulations. It is shown that it can be approximated by a Gaussian function under some conditions. The D'Agostino-Pearson normality test is used to assess the risk alpha of the approximation. In order to classify a brain into three types of brain tissue and deal with the problem of partial volume effects, the proposed algorithm uses two steps: 1) segmentation of the brain into pure and mixclasses using the mixture model; 2) reclassification of the mixclasses into the pure classes using knowledge about the obtained pure classes. Both steps use Markov random field (MRF) models. The multifractal dimension, describing the topology of the brain, is added to the MRFs to improve discrimination of the mixclasses. The algorithm is evaluated using both simulated images and real MR images with different T1-weighted acquisition sequences. PMID- 11212367 TI - Modeling the haemodynamic response in fMRI using smooth FIR filters. AB - Modeling the haemodynamic response in functional magnetic resonance (fMRI) experiments is an important aspect of the analysis of functional neuroimages. This has been done in the past using parametric response function, from a limited family. In this contribution, we adopt a semi-parametric approach based on finite impulse response (FIR) filters. In order to cope with the increase in the number of degrees of freedom, we introduce a Gaussian process prior on the filter parameters. We show how to carry on the analysis by incorporating prior knowledge on the filters, optimizing hyper-parameters using the evidence framework, or sampling using a Markov Chain Monte Carlo (MCMC) approach. We present a comparison of our model with standard haemodynamic response kernels on simulated data, and perform a full analysis of data acquired during an experiment involving visual stimulation. PMID- 11212368 TI - An active contour model for measuring the area of leg ulcers. AB - Leg ulcers are chronic skin wounds that affect many people and take a long time to heal. The progress of wound healing and the effect of clinical treatments can be monitored partly by measuring the area of the wound. Measurements taken via manually based methods, such as using a computer pointing device to delineate the wound boundary in a digitized image, suffer from variations due to manual dexterity and differences of opinion between observers. An active contour model is presented that models the contour using piecewise B-spline arcs and uses the minimax principle to adaptively regularize the contour according to the local conditions in the wound image. The model makes use of the existing manual delineation process in order to initialize the solution and is shown to reduce the effect of the inherent variations upon the repeatability and consistency of area measurements in many cases. PMID- 11212369 TI - Edge-guided boundary delineation in prostate ultrasound images. AB - Accurate detection of prostate boundaries is required in many diagnostic and treatment procedures for prostate disease. In this paper, a new paradigm for guided edge delineation is described, which involves presenting automatically detected prostate edges as a visual guide to the observer, followed by manual editing. This approach enables robust delineation of the prostate boundaries, making it suitable for routine clinical use. The edge-detection algorithm is comprised of three stages. An algorithm called sticks is used to enhance contrast and at the same time reduce speckle in the transrectal ultrasound prostate image. The resulting image is further smoothed using an anisotropic diffusion filter. In the third stage, some basic prior knowledge of the prostate, such as shape and echo pattern, is used to detect the most probable edges describing the prostate. Finally, patient-specific anatomic information is integrated during manual linking of the detected edges. The algorithm was tested on 125 images from 16 patients. The performance of the algorithm was statistically evaluated by employing five expert observers. Based on this study, we found that consistency in prostate delineation increases when automatically detected edges are used as visual guide during outlining, while the accuracy of the detected edges was found to be at least as good as those of the human observers. The use of edge guidance for boundary delineation can also be extended to other applications in medical imaging where poor contrast in the images and the complexity in the anatomy limit the clinical usability of fully automatic edge-detection techniques. PMID- 11212370 TI - A novel approach to extract colon lumen from CT images for virtual colonoscopy. AB - An automatic method has been developed for segmentation of abdominal computed tomography (CT) images for virtual colonoscopy obtained after a bowel preparation of a low-residue diet with ingested contrast solutions to enhance the image intensities of residual colonic materials. Removal of the enhanced materials was performed electronically by a computer algorithm. The method is a multistage approach that employs a modified self-adaptive on-line vector quantization technique for a low-level image classification and utilizes a region-growing strategy for a high-level feature extraction. The low-level classification labels each voxel based on statistical analysis of its three-dimensional intensity vectors consisting of nearby voxels. The high-level processing extracts the labeled stool, fluid and air voxels within the colon, and eliminates bone and lung voxels which have similar image intensities as the enhanced materials and air, but are physically separated from the colon. This method was evaluated by volunteer studies based on both objective and subjective criteria. The validation demonstrated that the method has a high reproducibility and repeatability and a small error due to partial volume effect. As a result of this electronic colon cleansing, routine physical bowel cleansing prior to virtual colonoscopy may not be necessary. PMID- 11212371 TI - Rapid 3-D cone-beam reconstruction with the simultaneous algebraic reconstruction technique (SART) using 2-D texture mapping hardware. AB - Algebraic reconstruction methods, such as the algebraic reconstruction technique (ART) and the related simultaneous ART (SART). reconstruct a two-dimensional (2 D) or three-dimensional (3-D) object from its X-ray projections. The algebraic methods have, in certain scenarios, many advantages over the more popular Filtered Backprojection approaches and have also recently been shown to perform well for 3-D cone-beam reconstruction. However, so far the slow speed of these iterative methods have prohibited their routine use in clinical applications. In this paper, we address this shortcoming and investigate the utility of widely available 2-D texture mapping graphics hardware for the purpose of accelerating the 3-D algebraic reconstruction. We find that this hardware allows 3-D cone-beam reconstructions to be obtained at almost interactive speeds, with speed-ups of over 50 with respect to implementations that only use general-purpose CPUs. However, we also find that the reconstruction quality is rather sensitive to the resolution of the framebuffer, and to address this critical issue we propose a scheme that extends the precision of a given framebuffer by 4 bits, using the color channels. With this extension, a 12-bit framebuffer delivers useful reconstructions for 0.5% tissue contrast, while an 8-bit framebuffer requires 4%. Since graphics hardware generates an entire image for each volume projection, it is most appropriately used with an algebraic reconstruction method that performs volume correction at that granularity as well, such as SART or SIRT. We chose SART for its faster convergence properties. PMID- 11212372 TI - X-ray CT metal artifact reduction using wavelets: an application for imaging total hip prostheses. AB - Traditional computed tomography (CT) reconstructions of total joint prostheses are limited by metal artifacts from corrupted projection data. Published metal artifact reduction methods are based on the assumption that severe attenuation of X-rays by prostheses renders corresponding portions of projection data unavailable, hence the "missing" data are either avoided (in iterative reconstruction) or interpolated (in filtered backprojection with data completion; typically, with filling data "gaps" via linear functions). In this paper, we propose a wavelet-based multiresolution analysis method for metal artifact reduction, in which information is extracted from corrupted projection data. The wavelet method improves image quality by a successive interpolation in the wavelet domain. Theoretical analysis and experimental results demonstrate that the metal artifacts due to both photon starving and beam hardening can be effectively suppressed using our method. As compared to the filtered backprojection after linear interpolation, the wavelet-based reconstruction is significantly more accurate for depiction of anatomical structures, especially in the immediate neighborhood of the prostheses. This superior imaging precision is highly advantageous in geometric modeling for fitting hip prostheses. PMID- 11212373 TI - A perspective on needle artifacts in MRI: an electromagnetic model for experimentally separating susceptibility effects. AB - A thorough understanding of artifacts caused by metallic instruments is essential for the guidance of interventional procedures by magnetic resonance imaging (MRI), because the accurate localization of each instrument is mandatory for this. In the past, this problem has been addressed by several groups, using theoretical, as well as experimental approaches. The artifacts associated with MRI are caused by geometry distortion and intravoxel dephasing. Usually, both effects mingle in the image, and depending on the pulse sequences and its parameters used for data acquisition, these effects are reflected in the image with different magnitude. In this paper we shortly present the well-known mathematical background of the two underlying effects. Mathematically, both can be treated separately. Here, we propose a new electromagnetic model which also allows to experimentally separate the effects better than by comparing spin-echo and gradient-echo images of the same object. With this new model, both effects geometry distortion and intravoxel dephasing-are demonstrated separately using the same gradient-echo pulse sequence for all scans and adjusting the fields of the model properly. Furthermore, as this model allows to adjust both effects independently, it is used to study different weightings of both effects when they appear simultaneously in the image. PMID- 11212374 TI - AM-FM texture segmentation in electron microscopic muscle imaging. AB - This paper describes the application of an amplitude modulation-frequency modulation (AM-FM) image representation in segmenting electron micrographs of skeletal muscle for the recognition of: 1) normal sarcomere ultrastructural pattern and 2) abnormal regions that occur in sarcomeres in various myopathies. A total of 26 electron micrographs from different myopathies were used for this study. It is shown that the AM-FM image representation can identify normal repetitive structures and sarcomeres, with a good degree of accuracy. This system can also detect abnormalities in sarcomeres which alter the normal regular pattern, as seen in muscle pathology, with a recognition accuracy of 75%-84% as compared to a human expert. PMID- 11212375 TI - A Jini service to reconstruct tomographic data. AB - Distributed computing that uses dynamic networks will change the way we work and communicate thanks to the interaction of devices and services, that are automatically added and removed from the network as needed. The Jini technology, which is built atop the Java programming language, provides a homogenous view of the network and extends the ability of code to migrate in Java. This software design model simplifies the configuration and access to hardware devices and software services in a network. Thus, it becomes possible to execute new services without pre-installing software on client machines. This new programming paradigm is especially important in medical applications, where the reliable transmission of information is essential. This paper demonstrates how single photon emission computerized tomography data can be iteratively reconstructed using a Jini service. PMID- 11212376 TI - Evaluation of the adaptive speckle suppression filter for coronary optical coherence tomography imaging. AB - During the last few years, optical coherence tomography (OCT) has demonstrated considerable promise as a method of high-resolution intravascular imaging. The goal of this study was to apply and to test the applicability of the rotating kernel transformation (RKT) technique to the speckle reduction and enhancement of OCT images. The technique is locally adaptive. It is based on sequential application of directional masks and selection of the maximum of all outputs. This method enhances the image features by emphasizing thin edges while suppressing a noisy background. Qualitatively, the RKT algorithm provides noticeable improvement over the original image. All processed images are smoother and have better-defined borders of media, intima, and plaque. The quantitative evaluation of RKT performance showed that in terms of average contrast-to-noise ratio, there is a significant improvement in image quality between original and enhanced images. The RKT image enhancement technique shows great promise in improving OCT images for superior boundary identification. PMID- 11212377 TI - Estimating the keratoconus index from ultrasound images of the human cornea. AB - The keratoconus index (KI) is a new biometric parameter to make diagnosis and to follow the development of the keratoconus in human eyes. Using images from an ultrasound biomicroscope, we show a semi-automatic method to speed up the computation of the KI. PMID- 11212379 TI - Polymorphism of the D12S66 system in the Japanese population and its detection using degraded DNA. AB - The short tandem repeat (STR) polymorphism of the locus D12S66 was amplified by PCR and analyzed by denaturing polyacrylamide gel electrophoresis followed by silver staining. Among 190 DNA samples from the Japanese population, six alleles were observed. The genotypic distribution meets Hardy-Weinberg expectations, and the heterozygosity was 52.7%. When sequences of the allelic products were compared, each allelic segment was 153-173 bp in size, and contained 9 to 14 GATA tetranucleotide repeat motifs. Amplification of the locus using 27 tooth and blood stain samples as sources of degraded DNA resulted in low backgrounds and reproducible patterns, suggesting the usefulness of the application of this locus for material examination. PMID- 11212378 TI - Characteristics of event related potentials elicited by trains of teeth clenching in humans. AB - Event related potentials were recorded on the human scalp during a foot pedal task, a hand gripping task, and a teeth clenching task. These were carried by targeting four trains of clicks, each at an interval of 1 sec, which were repeated 20 times at random frequencies. The brain potentials were recorded from midline-frontal (Fz), -central (Cz) and -parietal (Pz) sites using surface electrodes. Positive potentials like P3 were elicited predominantly at the frontal site (Fz); those for the clenching task were slower and smaller. The magnitudes of the P3 potentials showed rough facilitation with trains of movement of the tasks. If it is assumed that the observed potentials involve an inhibition or reset of motor neurons referring to the tasks, the facilitation might be expedient for the neurons to recover the potential condition more quickly, which is important in preparing for the next action. PMID- 11212380 TI - Primary insertion of implants in the zygomatic bone following subtotal maxillectomy. AB - A case of maxillary carcinoma treated with primary insertion of Branemark implants into the zygomatic bone following subtotal maxillectomy is reported. This method has several advantages. First, early detection of postoperative recurrence is easier than with closing the flap. Second, when the implant is inserted into the midfacial region, zygomatic bone can be useful because of thickness. In addition, applying a maxillary prosthesis in the early stages avoids contracture of facial soft tissue. This primary reconstructive method is effective in cases of preserved zygoma after total maxillectomy. PMID- 11212381 TI - Assessing the image quality of a CCD-based digital intraoral radiography system: application of perceptibility curve test. AB - The perceptibility curve test is a method for evaluating the psychophysical properties of radiographic systems. The concept of the perceptibility curve is based on the minimum perceptible exposure differences that are recorded by a particular imaging system. The perceptibility curve test was applied to a Charge Coupled Device (CCD)-based digital intraoral radiography system in this study. A test object was made of a square aluminum block, 28 mm in both height and length and 10 mm in thickness. The test object had ten contrast details in the form of round holes with diameters of 1.5 mm. The depths of the holes ranged from 0.05 mm to 0.5 mm in steps of 0.05 +/- 0.01 mm. An X-ray unit was used that operated in the range of 60 to 90 kVp. Test radiographs were shown to observers in random order. Six observers were asked to rate them regarding the number of spots representing holes that they could perceive. The smallest perceptible difference in gray level on the computer monitor, a 15-inch cathode-ray tube (CRT), was then found. The minimum difference in gray level between a perceptible detail and the background was determined. Dose response functions were employed to determine exposures corresponding to these gray levels. For each case, delta logE as a function of the number of object details was calculated. Finally the reciprocal of all values of (delta logE)min were calculated. The number of details which the observers perceived decreased linearly with decreasing delta logE values. The maximum number of details that observers perceived was eight or nine. The perceptibility curves showed that their peaks shifted slightly with a change of the kVp but that their shapes were similar at different kVp settings. PMID- 11212382 TI - Apical microsurgery for failed endodontics. AB - The operating microscope allows the surgeon unparalleled visualization of the root end structures for periapical surgery. The ultrasonic root end preparation tips enable debridement of the resected root end 2 to 4 mm in the long axis of the root. These advances have allowed periapical surgery to be performed at a new level of excellence with, we believe, more predictable healing. PMID- 11212383 TI - Necrotizing fasciitis and mediastinitis. AB - Necrotizing fasciitis and mediastinitis are two rare but grave complications of orofacial infections. The clinical presentation, diagnostic modalities, anatomic pathways, microbiologic make-up, surgical management, and the use of adjuvant HBO therapy for both entities have been discussed. PMID- 11212384 TI - Infections of the jaws, including infected fractures, osteomyelitis, and osteoradionecrosis. PMID- 11212385 TI - Surgical treatment of periodontal infections. PMID- 11212386 TI - Peri-implant infections. AB - The most judicious way to address peri-implant disease is to take steps to avoid it from the beginning of each implant restoration case. This involves treatment planning with a priority placed on biomechanically overengineering the case, using sound surgical techniques, enhancing keratinized tissue prior to placing the implants when appropriate, and placing an emphasis on rigorous follow-up and hygiene instruction. In the long run, the benefits of adhering to such methods outweigh the disadvantages. Careful attention to these guidelines leads to a less stressful practice and fewer cases of peri-implantitis. It should also increase our dental implant success rates and predictability of outcome even further. PMID- 11212387 TI - Team approach for closure of oroantral and oronasal fistulae. AB - Oroantral and oronasal fistulas present with a broad range of causation, size, duration, and extent of infection involving the nose and paranasal sinuses. Accurate diagnosis of the extent of the disease with appropriate radiographic evaluation will guide the surgeon to select an approach that addresses all of the infected sites. When significant sinus disease is found, an endoscopic approach to restoring drainage in all of the involved sinuses can promote predictably successful closure of oroantral and oronasal fistulas. The multispecialty team approach to this disease, with the concomitant management of the sinusitis and fistula closure, is a significant advance in the successful management of this chronic condition. PMID- 11212388 TI - Surgical management of orofacial infections. AB - This overview of the surgical management of orofacial odontogenic infections is designed as a practical guide for the oral and maxillofacial surgeon. Fortunately, the incidence of serious odontogenic infections is decreasing. This decreased frequency, however, necessitates diligent study and mental preparation in advance of the emergent situations in which such cases present. PMID- 11212389 TI - The fifth commandment: honor your father and your mother. PMID- 11212390 TI - Juggling hats. PMID- 11212391 TI - Difficult parents, desperate children. PMID- 11212392 TI - Another look at long-term care insurance. PMID- 11212393 TI - [Cytotoxic and cytostatic effect of avermectines on tumor cells in vitro]. AB - Effect of natural avermectin complex (aversectin C) and separate avermectins A1, A2, B1 and B2 in the cell culture of murine myeloma Ns/o, Erlich carcinoma ascites and human larynx carcinoma Hep-2 was investigated. It was shown that aversectin C within the concentrations of 0.1 to 1.0 mcg/ml inhibited proliferation of tumor cells and induced their death. Proliferation inhibition was due to the delay of the cells cycle start (lag-phase prolongation) and blocking of mitotic cycle. Ns/o cells death had apoptosis signs: chromatin condensation and fragmentation, DNA fragmentation. It was demonstrated that only avermectin A1 has cytotoxic activity within the concentrations used, avermectins A2 and B2 had cytostatic activity, avermectin B1 showed no activity under the experimental conditions. PMID- 11212394 TI - [Microbiological evaluation of antibiotics for empirical therapy of community acquired infections of the lower respiratory tract]. AB - During first 3 days after patient hospitalization with pneumonia or chronic obstruction pulmonary disease (COPD) pathogens in sputum were studied according NCCLS standards (for 1999 year). Among 93 pathogens isolated in pneumonia the most frequent were S. pneumoniae (41.9%), H. influenzae (21.5%). Among 232 pathogens isolated in COPD the most frequent were S. pneumoniae (35.5%), H. influenzae (16.8%). Other pathogens were staphylococci, moraxella, gram-negative bacteria. No penicillin-resistant S. pneumoniae, were isolated, the strains with moderate penicillin resistance were less than 3% in both groups. Among H. influenzae isolated from patients with pneumonia 25% were beta-lactamase producers, from COPD patients 21% strains produced beta-lactamase. Totally among all studied pathogens only 58% were sensitive to ampicillin in pneumonia groups and 48% in COPD groups, for azithromycin 70.7% and 71% respectively, for cefuroxime 84.5% and 85% respectively. Ampicillin efficacy for empirical treatment of community-acquired low respiratory tract infections was substantially less than that of modern antibiotics. PMID- 11212395 TI - [Fluorine level in the bone and cartilage in children treated with ciprofloxacin (data obtained from the femur distal part]. AB - Comparative data on the content of fluorine in various sections of the left femur distal part, i.e. spongy bone, process zone and articular cartilage are presented. The examination was performed on postmortem sections from 10 pediatric cases (the average age of 9.5 years) with mucoviscidosis or aplastic anemia treated before the death for up to 12 months with ciprofloxacin in a dose of 20 to 40 mg/kg body weight. The control postmortem sections were from 10 practically healthy children (the average age of 10.4 years) killed in a car accident. The sections were subjected to 2-stage dry ashing with ionometric determination of the fluorine ions. The results were treated according to the V.Yu. Urbach procedure. It was shown that the content of fluorine in the sponge bone and process zone in both the groups did not significantly differ. A comparatively high content of fluorine was detected only in the postmortem sections of the articular cartilage from the children of the main group who however had no chondrotoxic symptoms while alive. That means that the difference is statistically and clinically insignificant. PMID- 11212397 TI - [Azithromycin (sumamed)--basic properties and therapy of community-acquired pneumonia]. PMID- 11212396 TI - [Disruption of microbiocenosis of the large intestine and the immune and interferon status in children with bacterial complications of acute viral infections of the respiratory tract and their correction by high doses of bifidumbacterin forte]. AB - One hundred and twenty-nine children with acute viral and bacterial infection of the respiratory tract were examined and disturbance of the large intestine microflora was detected. It was characterized by significant reduction of lactobacilli, moderate growth of opportunistic bacteria and higher contents of Candida. Changes in T- and especially B-cellular immunity were observed in 35 per cent of the patients. In patients with decreased avidity of the immunoglobulins G in the peripheral blood the changes were observed in 82-100 per cent of the cases. In the majority of the patients the capacity for interferon genesis was suppressed. A shorten course (5 days) of the bifidumbacterin forte therapy in a dose of not less than 10(9) CFU/ml. normalized the intestinal microflora, improved the indices of the B- and T-cellular immunity (including the subpopulation of the T-helper cells but not the T-suppressor cells), stimulated NK and improved the ability to induce alfa- and gamma-interferons of the peripheral blood leukocytes. The experience with using high doses of bifidumbacterin forte was evident of its good tolerance and possible value in increasing the patient resistance to infection. PMID- 11212398 TI - [Prospects of development of drugs for therapy of gram-positive bacterial infections]. PMID- 11212400 TI - [Biosynthesis of the non-polyene antibiotic imbricin in the medium containing the producer culture filtrate]. AB - Imbricin (macrolide nonpolyen antibiotic) biosynthesis conditions was investigated in the medium containing culture filtrate of its producer- Streptomyces imbricatus. It was demonstrated that filtrate contains some regulator substance affecting the antibiotic biosynthesis and metabolism processes of actinomycetes S. imbricatus. Maximum of regulator accumulation coincides with maximum of antibiotic biosynthesis, and amount of synthesized imbricin is proportional to the amount of the culture filtrate added to the medium. When low active mutant of S. imbricatus was grown in the medium with added regulator its activity achieved the control level. It was shown that stimulating activity of the producer's culture filtrate is not connected with pH changes or with supplement with some additional nutritional substrates. PMID- 11212399 TI - [General trends in design of drugs for chemotherapy of AIDS]. PMID- 11212402 TI - [Prolonged hypothermia refractory to active warming with air convection]. PMID- 11212401 TI - [Locoregional anesthesia for external ear surgery and postoperative analgesia]. AB - OBJECTIVES: To evaluate a change in the classical technique for local-regional anesthesia (periauricular "V" infiltration) for surgery on the outer ear, specifically adding a new infiltration of the osteocartilaginous juncture of the external acoustic meatus and the auditory foramen, as an alternative to general anesthesia in adults, including assessment of postoperative analgesia. PATIENTS AND METHODS: The new technique was used in 45 operations on 23 patients. We analyzed pain during and after surgery on a simple verbal scale. RESULTS: After modifying the technique it was possible to perform surgery on the outer ear without causing pain, patients reporting "0" pain on a scale of 0 to 10. Eight patients reported "0" for postoperative pain, while one assessed pain as "4" and one as "2". No signs of emesis or cardiac events were observed. CONCLUSIONS: The described local-regional blockade of the outer ear used as the only anesthetic method, is indicated for both cosmetic surgery and repair of outer ear injuries, given its excellent analgesia during and after surgery. The characteristics of this type of block of the pavilion make it ideal for major outpatient surgery and a valid alternative to general anesthesia in adults. PMID- 11212403 TI - [Eisenmenger syndrome in a patient with persistent ductus arteriosus and septic shock]. PMID- 11212404 TI - [Combined subarachnoid-epidural anesthesia technique using a double catheter in lower limb revascularization surgery]. PMID- 11212405 TI - [Early detection of hyperkalemia caused by reperfusion during liver transplantation using neuromuscular block monitoring]. PMID- 11212406 TI - [Anesthesia considerations in West syndrome]. PMID- 11212407 TI - Blurred relationship between periodontist and the general practitioner. PMID- 11212408 TI - Smile-maxilla, maxilla in the mouth, and other interdisciplinary design guidelines: helpful hints for the esthetic dental team. PMID- 11212409 TI - Advantages and limitations of nonsurgical periodontal therapy in the management of chronic periodontitis. PMID- 11212410 TI - Initial preparation: anti-infective therapy. AB - The primary aim of anti-infective therapy is to eliminate or reduce the subgingival plaque and to arrest tissue breakdown associated with chronic or progressive periodontitis. Four to six weeks following anti-infective therapy, initial healing is usually complete, and the clinical status should be re evaluated. After assessing the reduction in probing depths, bleeding on probing and clinical attachment levels, the clinician must decide whether the anti infective therapy has arrested the disease. If it is determined that maximum healing has occurred, the initial phase of therapy is complete, and the patient is placed into the maintenance program. In sites that remain > or = 6 mm following anti-infective therapy, surgical debridement may be indicated to increase visualization of the roots for deposit removal because the evidence points to better calculus removal in an open versus closed environment. During surgical root preparation, fine diamonds or finishing burs produce the smoothest root surface followed by manual and power-driven scalers. Endoscopic cameras that enable the clinician to see subgingival calculus without benefit of surgical access may prove to be a valuable diagnostic tool for sites that do not respond to therapy. Diamond-coated ultrasonic inserts are available from some manufacturers and have been shown to be efficient and effective in surgical root preparation. New designs and finer grits may enable clinicians to use these instruments in nonsurgical applications in the future. Finally, new evidence from one group in Belgium has shown that significantly more attachment gain and probing depth reduction is achieved when scaling and root planing is done in one or two visits within 24 hours compared with the traditional method of scaling quadrant by quadrant over four visits. These preliminary results need to be confirmed by others but hold a great deal of promise for improving the outcomes from nonsurgical root preparation in the future. PMID- 11212411 TI - Regenerative materials: an overview. AB - Periodontal reconstructive therapies have demonstrated the ability to reverse the destruction due to periodontitis provided that they are implemented according to their individual indications. By properly evaluating a site, one can employ an evidence-based approach to effectively and predictably treat intrabony defects and furcation involvements. It also should be emphasized that a thorough evaluation of the therapeutic outcome should be continuously performed on all sites in order to determine treatment success and the possible need for further intervention. This is based on the long-term follow-up of cases treated with regenerative therapies, which have shown maintenance of results if the patient had good oral hygiene and was enrolled in a proper maintenance program. With respect to the preceding discussion: 1. The main periodontal reconstructive therapies employed by periodontists are GTR, bone replacement grafts and biologic mediators. 2. It is possible to achieve regeneration when using barriers, autografts, allografts, bovine-derived xenografts and EMDs. 3. Currently, regenerative techniques can be used for the treatment of intrabony defects and furcation involvements given the proper evaluation of each individual site. 4. Various regenerative materials are capable of achieving similar results in intrabony defects and are very predictable when employing evidence-based treatment. 5. A combination of regenerative materials such as barriers and grafts in intrabony defects has not demonstrated any improvement over their use alone. 6. A combination of regenerative materials such as barriers and grafts in mandibular class II furcations has demonstrated improvement over the use of the graft or barrier alone. 7. A combination of regenerative materials such as barriers and grafts in maxillary class II furcations has some limited evidence to support improvement over the use of the graft or barrier alone, but the predictability should not be considered high. 8. A combination of regenerative materials such as barriers and grafts in class III furcations has very limited evidence to support improvement over the use of the graft or barrier alone and should not be considered predictable. 9. Beyond the initial healing phase postsurgically, maintenance and oral hygiene play the largest role in long-term therapeutic success. PMID- 11212412 TI - Worldwide advancement of anesthesia in dentistry. PMID- 11212414 TI - Simulation technology in anesthesiology. PMID- 11212413 TI - Sevoflurane and isoflurane reduce oxygen saturation in infants. AB - Volatile anesthetics are generally known to exert several influences on the respiratory system, but their direct effect on oxygen saturation as measured by pulse oximetry (SpO2) in infants remains unknown. In this study, 70 infants under 2 years of age who received general anesthesia were examined to determine the effects of several volatile anesthetics and nitrous oxide on SpO2. After endotracheal intubation, the subjects were ventilated using a Jackson-Rees circuit with oxygen, nitrous oxide, and either sevoflurane, enflurane, or isoflurane adjusted to twice the adult minimum alveolar concentration (MAC) for the agents when used in combination with 67% nitrous oxide. In all cases, the end tidal carbon dioxide tension (PetCO2) was maintained within the same range (28-35 mm Hg). Significantly lower SpO2 values (paired t test, P < .05) were observed when the subjects were ventilated with oxygen, 67% nitrous oxide, and sevoflurane or isoflurane--but not with oxygen, 67% nitrous oxide, and enflurane--than when they were administered oxygen, 50% nitrous oxide, and the original concentration of each volatile anesthetic. These results suggest that sevoflurane and isoflurane have different effects from enflurane on gas exchange systems. PMID- 11212415 TI - "Read and understand" vs. "a competency-based approach" to designing, evaluating, and validating SOP training. PMID- 11212416 TI - Comparative hemolytic activity of undiluted organic water-miscible solvents for intravenous and intra-arterial injection. AB - In humans, nonaqueous solvents are administered intravascularly in two kinds of situations. They have been used in subcutaneous or intramuscular pharmaceutical formulations to dissolve water-insoluble drugs. The need for these vehicles had increased in recent years, since the drug development process has yielded many poorly water-soluble drugs. The use of water-miscible nonaqueous solvents in therefore one of the approaches for administering these products as reference solutions useful in formulation bioequivalence studies. The intravascular use of organic solvents has also gained importance owing to a new approach for the treatment of cerebral malformations using precipitating polymers dissolved in water-miscible organic solvents. At present, the solvent most commonly used for the liquid embolics to solubilize the polymers is dimethyl sulfoxide, which exhibits some local and hemodynamic toxicities. In order to find new, less toxic vehicles for pharmaceutical formulations for the intravenous and intra-arterial routes and for embolic materials, 13 water-miscible organic solvents currently used (diluted with water) for pharmaceutical applications, were evaluated in this study. Their hemolytic activity and the morphological changes induced when mixed with blood (1:99, 5:95, 10:90 solvent:blood) were estimated in vitro. From these data, the selected organic solvents could be subdivided into four groups depending on their hemolytic activity: very highly hemolytic solvents (ethyl lactate, dimethyl sulfoxide), highly hemolytic solvents (polyethylene glycol 200, acetone), moderately hemolytic solvents (tetrahydrofurfuryl alcohol, N-methyl-2 pyrrolidone, glycerol formal, ethanol, Solketal, glycofurol) and solvents with low hemolytic activity (propylene glycol, dimethyl isosorbide, diglyme). PMID- 11212417 TI - Chemical sterilization with peracetic acid: permeation risks inside parenteral infusion fluid. PMID- 11212418 TI - One-way distribution system for water for injection: process management, microbiological quality control, and meeting regulatory requirements. AB - The specifications for pharmaceutical water, the qualification and validation of water preparation facilities, strategies to prevent contamination by water-borne bacteria and lastly, the monitoring of microbiological purity are the topics of frequent seminars on Pharma Water Total Quality Management. The same subdivisions are used in the following paper on the process management and microbiological control of a one-way distribution system for Water for Injection. Since 1990, such a system has been in use in the production department of Pharma Hameln GmbH, a contract manufacturer of parenterals. Using this system as an example, the twin needs for flawless microbiological process control and for suitable measures to monitor water quality are discussed, which, together with extensive documentation of the qualification of the production and distribution system, ultimately led to acceptance of the system by regulatory authorities. PMID- 11212420 TI - A validated calibration method for hydrogen peroxide vapour sensors. AB - A method of calibrating hydrogen peroxide vapour sensors is described which is based on the well-defined saturated vapour pressures of hydrogen peroxide over its aqueous solutions at fixed temperatures. The calibration technique was developed for use with amperometric gas sensors but could be applied to other sensor types. The method can be used over the entire range of vapour pressures that are likely to be of practical interest in the context of isolator sterilisation and has been reliably validated by quantitative volumetric analysis. The method depends not only on the well understood underlying principles but also on the solution of practical problems associated with ensuring full saturation of the carrier gas stream and, simultaneously, the elimination of aerosol droplets which might otherwise interfere with the calibration. PMID- 11212419 TI - Activities of the USP Microbiology Subcommittee of Revision during the 1995-2000 revision cycle. AB - This article is a comprehensive review of the published activities of the Microbiology Subcommittee of the USP Committee of Revision for the 1995-2000 revision cycle. The activities of this revision cycle were designed to position USP activities in microbiology that will be useful as technology advances. In addition to reviewing the changes accomplished, this article discusses the rationale for many of the changes and some background information on new initiatives underway. Where appropriate, changes in the USP that did not fall under the direct purview of the MCB Subcommittee but of interest to the microbiology community are also discussed. PMID- 11212422 TI - Case report: successful use of rectally administered levodopa-carbidopa. PMID- 11212423 TI - National Family Medicine Resident Survey. Part 1: Learning environment, debt, and practice location. PMID- 11212421 TI - Diagnosing and managing delirium in the elderly. AB - OBJECTIVE: To outline current approaches to diagnosing and managing delirium in the elderly. QUALITY OF EVIDENCE: A literature review was based on a MEDLINE search (1966 to 1998). Selected articles were reviewed and used as the basis for discussion of diagnosis and etiology. We planned to include all published randomized controlled trials regarding management but found only two. Consequently, we also used review articles and recent practice guidelines for delirium published by the American Psychiatric Association. MAIN FINDINGS: Clinical diagnosis of delirium can be aided by using DSM-IV criteria, the Delirium Symptom Interview, or the confusion assessment method. Management must include investigation and treatment of underlying causes and general supportive measures. Providing optimal levels of stimulation, reorienting patients, education, and supporting families are important. Pharmacologic management of delirium should be considered only for specific symptoms or behaviours, e.g., aggression, severe agitation, or psychosis. Only one randomized controlled trial of tranquilizer use for delirium in medically ill people has been published. Findings support the current belief that neuroleptics are superior to benzodiazepines in most cases of delirium. Most authorities still consider haloperidol the neuroleptic of choice. Controlled trials of the new atypical neuroleptics for treating delirium are not yet available. Benzodiazepines with relatively short half-lives, such as lorazepam, are the drugs of choice for withdrawal symptoms. CONCLUSION: Delirium is frequently underdiagnosed in clinical practice. It should be suspected with acute changes in behaviour. Careful investigation of the underlying cause permits appropriate management. PMID- 11212424 TI - Drug interactions with St John's wort. PMID- 11212425 TI - Hypothesis: the Research Page. Welcome to the Research Page. PMID- 11212426 TI - Primary care and population health promotion. Collaboration between family physicians and public health units in Ontario. PMID- 11212427 TI - Drug information needs clarification. PMID- 11212428 TI - Time to fess up, authors! PMID- 11212429 TI - Josee and Richard. PMID- 11212430 TI - Cancer chemotherapy during pregnancy. Consortium of cancer in pregnancy evidence. AB - QUESTION: I have an 8-weeks' pregnant patient who was diagnosed with stage III Hodgkin's disease last week. The oncologist suggests delaying chemotherapy until the second trimester. What are the effects of chemotherapy on a fetus after the first trimester? Where can I find reliable information on the subject? ANSWER: Available data suggest that exposure to chemotherapy during the first trimester of pregnancy is associated with increased risk of major malformations. Exposure during the second and third trimesters does not result in major malformations, but could have nonteratogenic effects, such as low birth weight. The brain develops throughout pregnancy, and it could be affected later in pregnancy. PMID- 11212431 TI - Deep vein thrombosis. PMID- 11212432 TI - Forced treatment. PMID- 11212433 TI - Pharmacologic management of refractory depression. PMID- 11212434 TI - Good-quality medical advice on the Internet. PMID- 11212435 TI - Canadians without regular medical doctors. Who are they? AB - OBJECTIVE: Because having a regular medical doctor is associated with positive outcomes, this study attempted to determine the characteristics of Canadians without regular doctors so that alternative methods of delivering care to people with those characteristics can be studied. DESIGN: Secondary data analysis of the National Population Health Survey using bivariate analyses and logistic regression. PARTICIPANTS: A total of 15,777 respondents older than 20 years. MAIN OUTCOME MEASURES: Responses to the question "Do you have a regular medical doctor?" and analysis of 11 variables covering demographics, health status, and lifestyle factors. RESULTS: One in seven respondents did not have a regular doctor. Younger respondents, men, single people, poorer respondents, respondents who perceived themselves in better health, recent immigrants, those without confidants, and smokers were more likely not to have regular doctors. Comparing provinces, participants from Quebec were least likely to have regular doctors. CONCLUSION: Primary care reform might need to consider alternative ways of providing care to certain people. Future primary care programs could be targeted to improve coverage of relatively underserviced people, particularly men, people on low incomes, those without confidants, and recent immigrants. PMID- 11212436 TI - Does having regular care by a family physician improve preventive care? AB - OBJECTIVE: To assess whether regular care from a family physician is associated with receiving preventive services. DESIGN: Secondary analysis of the 1994 National Population Health Survey. SETTING: Cross-sectional sample of the Canadian population. PARTICIPANTS: A total of 15,731 non-institutionalized adults. MAIN OUTCOME MEASURES: Reported visits to general practitioners and specialists in the previous year and reports of having had blood pressure measurements, mammography, and Pap smears. RESULTS: A graded relationship was observed between level of regular care by a family physician in the previous year (none, some, regular) and receiving preventive services. Those without regular doctors and those reporting only some care by a family physician were less likely to have ever had their blood pressure checked than adults receiving ongoing care from a regular family physician. Women reporting some or no care were less likely to have had mammography within 2 years or to have ever had Pap smears. CONCLUSION: Adults who receive regular care from a family physician are more likely to receive recommended preventive services. PMID- 11212437 TI - Vitamin B12 injections versus oral supplements. How much money could be saved by switching from injections to pills? AB - OBJECTIVE: To estimate savings, using a third-party payer perspective, if all elderly patients currently receiving vitamin B12 (cobalamin) injections were switched to high-dose oral therapy. DESIGN: We modeled high-dose oral B12 supplement costs to include drugs, pharmacists' fees, and one-time conversion costs consisting of two physician visits and laboratory monitoring. The number of vitamin-injection visits avoided by switching to oral therapy was predicted using a multivariate model that considered covariates for overall patient illness. SETTING: Ontario family physicians' and internists' practices. PARTICIPANTS: Population-based administrative databases for Ontario were used to identify all people between 65 and 100 years who received parenteral vitamin B12 during 1995 and 1996. MAIN OUTCOME MEASURES: The cost of parenteral vitamin B12 for each patient, including drugs, injections, pharmacists' fees, and injection-associated physician visits, was measured directly from the databases. RESULTS: The annual cost of parenteral vitamin B12 therapy averaged $145.88 per person and totaled a maximum $25 million over 5 years. Converting all patients to high-dose oral B12 and treating them for 5 years would cost $7.4 million. Depending on how many vitamin-injection visits are avoided by switching to oral therapy, between $2.9 million and $17.6 million would be saved. Switching to oral B12 administration saved costs as long as 16.3% of injection-associated visits were avoided. CONCLUSION: Switching all patients from B12 injections to oral cobalamin therapy could result in substantial savings. PMID- 11212438 TI - Andropause. Testosterone replacement therapy for aging men. AB - OBJECTIVE: To review the rationale for treating symptomatic aging men whose testosterone levels are mildly reduced or low-normal with testosterone replacement therapy. QUALITY OF EVIDENCE: Large-scale multicentre prospective studies on the value of treating andropausal men with hormone therapy do not exist because the whole area of hormone therapy is barely 10 years old. Evidence presented is based on physiologic studies, particularly studies in which treatment has been assessed. These were largely uncontrolled open studies. Studies to date report positive responses to testosterone treatment with very few serious side effects. MAIN MESSAGE: Physicians should consider hypoandrogenism if male patients complain of loss of libido, erectile dysfunction, weakness, fatigue, lethargy, loss of motivation, or mood swings. Less obvious associations with reduced levels of testosterone are anemia and osteoporosis. The main cause of reduced testosterone production is primary gonadal insufficiency, but secondary causes, such as hypothalamic-pituitary disease, should be considered. Evidence shows that most men treated with testosterone will feel better about themselves and their lives. CONCLUSION: Andropause is a term of convenience describing a complex of symptoms in aging men who have low testosterone levels. Physicians should be aware of its existence, should consider ordering tests for men who have symptoms, and should treat carefully selected patients whose serum testosterone levels are low. PMID- 11212439 TI - Hunterian Lecture. What can we learn about mechanisms of mutation from a study of craniosynostosis? AB - Mutation may be defined simply as structural change affecting the genetic material. The generation of genetic variety by spontaneous mutational events has been the driving force behind evolution--without such mutation our complex human genome could not have evolved. However, as doctors, we more frequently encounter mutation in the context of human disease, whether in somatic cells as a cause of cancer, or in the germline as a cause of inheritable disease. In these contexts, the processes of mutagenesis are relevant to every field of medicine. Scientific study of mutational mechanisms has logically been founded in the relatively simple genetic systems of the prokaryotes and such lowly eukaryotes as the fruit fly. The study of human clinical genetics approaches the problem from quite the opposite direction--from that of the most highly evolved genetic system. Whilst this approach may be dependent less on logical progression and more on phenomenology, it nevertheless provides a complementary avenue for the observation and study of mutational mechanisms. The genetic research described in this article is firmly rooted in such phenomenology, based as it is on rare craniosynostosis syndromes. Over the past decade, there has been a deluge of molecular discoveries in the field of craniosynostosis. This promises improvements in classification, prognostication, pre-natal diagnosis, and perhaps ultimately for potential avenues for cure. However, exciting as these clinical prospects are, the research presented here has a different focus: it investigates the mechanistic basis underlying the craniosynostosis mutations, in the hope that such study may lead to insights applicable generally to the field of mutagenesis. PMID- 11212441 TI - A simple, effective and safe method for central venous catheter replacement. AB - With the possible exception of pulmonary artery catheters, central venous catheters (CVCs) have the highest rates of infection of all intravascular catheters, accounting for up to 90% of all vascular catheter-related bloodstream infections. The frequency of CVC-related infections is between 10-30%. PMID- 11212440 TI - Contrast-enhanced helical computerised tomography in the investigation of thoracic aortic injury. AB - Aortic angiography is widely considered the 'gold standard' for the diagnosis of traumatic thoracic aortic injury. Unfortunately, thoracic aortic angiography has many disadvantages: the technique is invasive but, more importantly, it is not routinely available in all hospitals, necessitating transfer of critically ill patients. Contrast-enhancement helical computerised tomography (CEHCT) of the thorax is rapidly becoming available, especially in more district general hospitals, and has been shown to be as sensitive and specific in detecting aortic trauma as angiography. This technique has the advantage of being non-invasive and is able to demonstrate injuries other than thoracic aortic disruption. We present four cases of traumatic thoracic disruption initially diagnosed using CEHCT in whom surgical repair was performed on the basis of the CEHCT findings. The surgical findings of aortic injury were correlated with CEHCT features. PMID- 11212442 TI - A stratified response system for the emergency management of the severely injured. AB - A decade ago, there were justifiable criticisms of the delivery of emergency care for injured patients in accident and emergency departments in the UK. To address this, a trauma management system was developed in 1991 at Alder Hey Hospital, Liverpool. This includes a trauma team, communication system, management guidelines and quality assurance. On admission to the accident and emergency department, injured patients are triaged to one of three levels of injury severity, and a multidisciplinary team lead by a paediatric surgeon or senior accident and emergency department physician is activated. The level of injury severity determines the composition of the trauma team. A care pathway based on ATLS/APLS principles has been developed. The response process as well patient management are documented and reviewed at a monthly audit meeting. Currently, more than 80% of eligible patients are managed using the trauma system, with an over-triage rate of about 25%. Regular modifications to the trauma system since its inception in 1991 have resulted in an efficient and effective management structure. Stratification of the trauma response has minimised unnecessary use of the multidisciplinary trauma team and ensures that mobilisation and use of hospital staff and resources are tailored to the needs of the injured patient. Although developed in a specialist children's hospital, the system could be adapted for any acute hospital. PMID- 11212444 TI - All basic surgical trainees should rotate through an accident and emergency post. AB - A 6-month post in accident and emergency is no longer compulsory for basic surgical training. Meanwhile, trauma teams have emerged in many UK hospitals to receive seriously injured patients, often with no involvement of basic surgical trainees (BSTs). This may lead to the appointment of surgical specialist registrars (SpRs) who have had little exposure to the initial management of seriously injured patients. This study documents the experience of a senior house officer undertaking a 6-month post in the accident and emergency department of a district general hospital. METHODS: Data concerning the nature of cases seen were collected retrospectively from all patient record cards signed by the author during the placement. RESULTS: During the period studied, the author was present in the resuscitation room on 41 occasions, of which 10 episodes involved the management of a multiply injured patient. A total of 159 fractures and significant soft tissue injuries in the upper limb and 122 such cases in the lower limb were seen. There were 25 head injuries, 17 spinal injuries, 5 significant cases of chest trauma, 4 of abdominal trauma and 5 significant urinary tract injuries. Some 86 practical procedures were carried out during the placement. DISCUSSION: The 6-month post in accident and emergency provided the BST with significant exposure to the care of seriously injured patients. Such a post should be compulsory to ensure that SpRs on appointment have already received exposure to managing the seriously injured. The post provided additional benefit in terms of performing practical procedures and exposure to other acute surgical conditions. PMID- 11212443 TI - The impact of trauma teams on basic surgical training. AB - An analysis of the number of trauma teams and the extent of involvement of basic surgical trainees in these teams in the South-West region is presented. PMID- 11212445 TI - Patients with acute skin loss: are they best managed on a burns unit? AB - Patients who are critically ill and have large areas of skin loss or breakdown present a difficult management problem. They require the combination of intensive therapy facilities to support failing organs and specialized skin care, sometimes including extensive debridement and reconstruction. The expertise required for both aspects of treatment are found uniquely on a burns unit. We present five patients with large areas of cutaneous loss or damage secondary to a variety of non-burn aetiologies who were managed on a burns unit. We suggest that a burns unit may be the most appropriate place for such patients to be treated during both the acute phase of their illness and the later stages of surgical reconstruction and physical rehabilitation. PMID- 11212446 TI - Oesophagogastric cancer and surgical subspecialisation: how much work? AB - The aim of this study was to assess the volume of work generated by one consultant (out of a surgical unit of seven) managing all the upper gastrointestinal malignancy in a district general hospital serving a population of 480,000. A 3-year period was prospectively audited and the volume of out patient and in-patient workload assessed with particular reference to resource management and levels of surgical staffing. Oesophagogastric cancer accounted for a mean of 61 new cases per year, representing 5.3% of new patient referrals. Assuming that a complex major operation for an oesophagogastric cancer equates to four intermediate equivalent values (IEVs), then this translated to a mean operative workload of 186 IEVs per year, representing 16.7% of the total elective operative workload of 1140 IEVs per year. Thus, all the oesophagogastric cancer was managed by a single firm as a speciality in a district general hospital over this 3-year period, though a relatively small proportion of new patients with oesophagogastric cancer translated into a significantly greater burden on the resources of consultant manpower and operating theatre time. PMID- 11212447 TI - Arthroscopy of the elbow for loose bodies. AB - This retrospective study confirms the benefit of arthroscopic removal of loose bodies from the elbow, and documents the accuracy of history and plain radiographs. In contrast to previous reports, patients with a diagnosis of osteoarthritis had a similar outcome to those with an alternative diagnosis. PMID- 11212448 TI - A study of waiting time for surgery in elderly patients with hip fracture and subsequent in-patient hospital stay. AB - OBJECTIVE: To establish whether increased waiting time to operation in elderly patients with hip fracture significantly affects postoperative time to discharge. METHODS: Combined prospective and retrospective analysis of theatre logbooks and in-patient data to determine the type, time and date of operation and subsequent in-patient stay. SETTING: A busy district general hospital in the South East Thames Valley area with changing availability of a dedicated trauma list. PATIENTS: 441 elderly patients undergoing hip surgery between May 1995 and March 1997. MAIN OUTCOME MEASURES: Waiting time from booking of operation to surgery and length of postoperative hospital stay. RESULTS: Increased pre-operative wait for emergency hip surgery in elderly patients significantly increases postoperative stay. Roughly doubling pre-operative wait increases postoperative stay by 19% (P < 0.01). PMID- 11212449 TI - Small bowel obstruction due to postoperative adhesions: treatment patterns and associated costs in 110 hospital admissions. AB - The workload and costs of the emergency admissions and treatment of adhesive small bowel obstruction (ASBO) are unclear. This review details and costs the admission workload of ASBO. All admissions over a 2-year period for ASBO at two district general hospitals were identified through ICD10 diagnostic codes. Diagnostic investigations, treatment patterns, ward stay and outcome information for admissions were detailed from clinical records to develop mean cost estimates and assess the associated workload. Of the 298 admissions identified, 188 were not due to ASBO and were excluded from analysis. Of the 110 admissions detailed, 41 (37%) were treated surgically and 69 (63%) conservatively. Most admissions occurred through general practitioner referral (86.4%) to accident and emergency (90.0%). Mean (SD) length of stay was 16.3 days (11.0 days) for surgical treatment and 7.0 days (4.6 days) for conservative treatment. In-patient mortality was 9.8% for the surgical group and 7.2% for the conservative group. Costs were based on the mean values from both centres for surgical and conservative admissions and detailed according to the cost of referral and follow up (100.98 Pounds surgical versus 102.61 Pounds conservative), hospital ward and ICU stay (3,327.48 Pounds versus 1,267.92 Pounds), theatre time (832.32 Pounds surgical only), investigations (282.73 Pounds versus 207.33 Pounds) and drug costs (133.90 Pounds versus 28.29 Pounds). Total treatment cost per admission for ASBO was 4,677.41 Pounds for surgically treated admissions and 1,606.15 Pounds for conservatively treated admissions. The impact of admissions for ASBO is considerable in terms of both costs and workload. Bed stay for these admissions represents the equivalent of almost one surgical bed per year and at least 2 days theatre time, impacting on surgical capacity and waiting lists. Adhesion prevention strategies may reduce the workload associated with ASBO. The review provides useful information for planning resource allocation. PMID- 11212450 TI - Ecthyma gangraenosum--a trap for the unwary. AB - Neutropaenic patients are at particular risk of developing a pseudomonal fasciitis known as ecthyma gangraenosum. Despite the similarities with necrotising fasciitis, Fournier's gangrene has a very different aetiology and management. PMID- 11212451 TI - Help of the fire brigade in a case of a strangulated penis. PMID- 11212452 TI - Is transurethral resection of the prostate safe and effective in the over 80-year old? AB - OBJECTIVE: To assess the safety and effectiveness of transurethral resection of the prostate (TURP) in patients over 80 years old. PATIENTS AND METHODS: The records of all patients over 80 years old undergoing TURP at one institution over a 3.5-year period were studied retrospectively. RESULTS: 31% of patients underwent TURP for symptoms and 68% for urinary retention. The early complication rate was 41%. The late complication rate was 22%. There were no deaths within 30 days of surgery. Of all patients, 80% were satisfied with the outcome of their operation. Of all patients with retention, 80% were able to void with small residual volumes by 6 weeks after operation. CONCLUSIONS: Although TURP in the over 80-year-old male is associated with significant morbidity, it is an effective treatment for urinary symptoms or retention. The majority of patients are able to void afterwards and are satisfied with the outcome of their surgery. PMID- 11212453 TI - Paediatric day-case surgery in a district general hospital: a safe option in a dedicated unit. AB - Currently, there is a trend towards the centralisation of paediatric surgery in specialist regional units. This study reports the results of 4 years' experience of paediatric day-case surgery in a dedicated unit within a district general hospital. Since its inception in 1993, data have been collected on all individuals undergoing surgery. Between 1993-1997, 804 operations were performed with 80% of procedures being undertaken by a consultant. There were 7 (< 1%) known complications and 7 (< 1%) patients required admission postoperatively. These results compare favourably with those of specialist institutions. PMID- 11212454 TI - Audit of referral practice to a fast-access breast clinic before the guaranteed 2 week wait. AB - Currently in the fast-access breast clinic at Eastbourne District General Hospital, the specialist determines the level of urgency of a referral. With the new '2-week wait' imposed by the Government since 1 April 1999, the determination of urgency has transferred to the general practitioner. Therefore, we decided to audit the current situation to see whether the guidelines were adequate for this change of emphasis. A total of 100 consecutive patients referred to the fast access breast clinic were evaluated to assess the quality of referrals and the effectiveness of the clinic. Only 80% of the referrals adhered to the guidelines; 73% of the referrals were deemed by the specialist to be urgent and seen within the 2-week time period. All patients who were subsequently diagnosed as having breast cancer were seen within 2 weeks. The audit indicates that further specific changes could be made to the guidelines to improve the referral practice. PMID- 11212456 TI - The CRABEL score--a method for auditing medical records. AB - Medical record keeping has become increasingly important particularly for research, audit and medico-legal purposes. The authors present a protocol, the CRABEL score, that is quick and easy to use for the assessment of the quality of medical record keeping with the purpose of standardizing the audit of medical records and improving their quality. PMID- 11212455 TI - An audit of general dental practitioners' referral practice following the distribution of third molar guidelines. AB - Oral and maxillofacial surgery waiting lists are amongst the longest of any surgical specialty. The majority of patients on these waiting lists have been referred for removal of their third molars (wisdom teeth). With increasing pressure to reduce the size of both out-patient and surgical waiting lists, it is important to ensure that only those patients with a recognised clinical need are referred and accepted for treatment. In April 1998, local general dental practitioners were issued guidelines for the management of patients with impacted third molars. This paper describes an audit that assessed the impact of this intervention. The results suggest that referral guidelines are an effective means of changing general dental practitioners' referral practice and that, used along with other strategies, could be effective in reducing oral and maxillofacial surgery out-patient and surgical waiting lists. PMID- 11212457 TI - The assessment of surgical skills and a simple knot-tying exercise. AB - Basic surgical skills courses are mandatory for all surgical trainees taking the MRCS examination. An important aspect of these courses is the level of practical skill achieved by junior surgeons attending them. We present a simple knot-tying exercise, which may be used to assess the baseline skill level of trainees at the outset of the course and against which their progress can be judged after tuition and practice. PMID- 11212458 TI - A short history of the dispensary movement in London from 1675 to 1948. PMID- 11212459 TI - Measles, mumps, rubella vaccine: through a glass, darkly. PMID- 11212460 TI - Genetic polymorphism and outcomes with azathioprine and 6-mercaptopurine. PMID- 11212462 TI - Accreditation: a two-edged sword. PMID- 11212461 TI - Profile of hospital admissions following acute poisoning--experiences from a major teaching hospital in south India. AB - This study was conducted to determine the incidence of hospital admissions following acute poisoning, nature of agents involved and change in pattern of poisoning over a 5-year period. Data from hospital records of all admissions to emergency department following acute poisoning collected prospectively were analysed for the period January 1993 to January 1998. A steady increase in deliberate poisoning using pesticides, particularly among young adults, was noted. Kerosene (paraffin) was the commonest poison in children and plant poisons were also common. There were 52 deaths (3.3%) among the 1584 admissions. The majority of deaths were due to pesticides. Poisoning and mortality followed ingestion of readily-available and commonly used agents. Measures to increase public education, counselling and awareness could prevent a number of these admissions. PMID- 11212463 TI - Visual hallucinations: a prevalence study among hospice inpatients. AB - The aim of the study was to determine the prevalence of visual hallucinations among hospice inpatients, and the prevalence of a number of possible associated risk factors. One hundred consecutive admissions to St. John's Hospice in Wirral were screened for visual hallucinations in a semi-structured interview. The prevalence of opioid administration, other drugs known to cause hallucinations, brain tumours, liver metastases, bone metastases, lung metastases, known renal failure, eye disease, Alzheimer's disease, Parkinson's disease, other neurodegenerative disorder, psychiatric disorder and epilepsy were also recorded. Subjects were screened for cognitive function using the Folstein mini-mental state examination (MMSE). Survival times from assessment to death were calculated. The results were analysed using arithmetical means with 95% confidence intervals (CI) and odds ratios with 95% confidence intervals. Almost half (47%) the patients had experienced visual hallucinations within the previous month. Hypnagogic or hypnopompic hallucinations of a person standing by the bedside were the commonest type. Median survival time for hallucinators was 15 days (range 0-50 days) and for non-hallucinators was 11 days (range 0-89 days). There was no significant difference in cognitive scores between hallucinators and non-hallucinators. Hallucinations were associated with multiple possible risk factors in every case. Hallucinators were more likely to be taking opioids, although the association was not strong (odds ratio 4.48, 95% CI = 1.6-12.19), and were taking larger numbers of potentially hallucinogenic drugs. It is not clear why some patients on opioids hallucinate and others do not. Data on the prevalence of various possible risk factors yielded ample material for the planning of future studies. PMID- 11212464 TI - Retrospective study of the use of hydromorphone in palliative care patients with normal and abnormal urea and creatinine. AB - An uncontrolled retrospective study was conducted looking at the use of oral controlled-release hydromorphone in palliative care patients. Over a 2-year period 55 patients were switched to hydromorphone therapy, and the efficacy and outcomes were assessed. Urea and electrolyte measurements were also recorded at the time of opioid switch and renal impairment defined as urea > 10.5 mmol/l and/or creatinine > or = 101 mmol/l. This group of 29 patients with abnormal urea and/or creatinine (Group 1) was compared with the remaining 26 patients (Group 2) who had normal urea and creatinine. The major reasons for change to hydromorphone were side-effects (cognitive/drowsiness/nausea) on previous therapy. Following a switch to hydromorphone these side-effects improved in over 80% of patients (n = 55). Comparison between Group 1 and 2 demonstrated a significant difference in renal function but no significant differences in reasons for change, dose of opioids or response to change (over 80% improvement following opioid switch). We conclude that hydromorphone is a flexible second-line alternative to morphine that is particularly useful when intolerable side-effects are experienced with other opioids. In renal impairment (including two patients with end-stage renal failure) we found hydromorphone to be safe and effective. Further clinical and pharmacokinetic studies are required. PMID- 11212465 TI - A prospective survey of the use of dexamethasone on a palliative care unit. AB - One hundred and six consecutive patients started on glucocorticosteroids (steroids) according to a defined prescription policy were surveyed each week to document the indications for use, any beneficial effect, any toxicity incurred and the reason for stopping. All patients had advanced malignant disease and survived for a median of 40.5 days (range 1-398+ days) from the start of steroid treatment. Fifty-seven per cent of patients completed three or more assessments. The most common specific indications for starting steroids were spinal cord compression, cerebral metastases, lymphangitis carcinomatosa and intestinal obstruction. The most common non-specific indications were anorexia, nausea, low mood, pain and vomiting. The median duration of steroid use was 21.5 days (range 1-89 days). The most common reason for the discontinuation of steroids was death or deteriorating condition. Symptom scores improved at some stage for the majority of patients started on steroids for anorexia, nausea, pain, low mood, vomiting and weakness but not in patients complaining of dyspnoea or poor mobility. The most common side-effects that were most probably attributable to steroid therapy were oral candidosis and proximal myopathy. The benefits of steroids when used according to defined guidelines were thought to outweigh toxicity. PMID- 11212466 TI - Diagnosis disclosure in a Portuguese oncological centre. AB - The disclosure of a diagnosis of cancer to patients is a controversial matter. There have been major differences in practice concerning this issue through time and between cultures. A questionnaire was sent to the doctors of the Oporto Centre of the Portuguese Institute of Oncology in order to assess their attitudes. We received 45 responses (40%) from the 113 questionnaires sent. Of these, 32 (71%) said that they disclose the diagnosis as a general policy or at the patients' request, and 13 (29%) disclose it rarely or not at all. The most frequent reason indicated by these 13 physicians was that the disclosure might damage the patients psychologically. Forty-four (98%) doctors inform the family of the diagnosis. Thirty-nine (87%) think that patients are satisfied with the information provided. This study was carried out in one oncological centre only, so it is inappropriate to conclude that this is what happens throughout Portugal. As far as we know, this is the first study in Portugal addressing this area of practice. This subject is a very important topic of research both in Portugal and in other countries, as many published recommendations are not research based. PMID- 11212467 TI - Palliative care and nursing homes: where next? AB - Specialist palliative care providers are seeking to transfer the principles of palliative care to more general care settings in order to meet the needs of people with diseases other than cancer. To prepare nursing home staff to provide palliative care increasing numbers of educational initiatives are now being offered. This paper explores some of the assumptions that underpin these initiatives. Recommendations are made that recognize the expertise already held within nursing homes and propose a collaborative approach to promote the appropriate integration of palliative care with nursing home practice. PMID- 11212468 TI - Is videotaping of consultations acceptable to patients attending a hospice day centre? AB - The use of a videotape recorder to analyse consultations in UK general practice is accepted, well established and has been extensively researched. The technique has potential in palliative medicine for training and the continuing assessment of communication skills as part of peer review. However, there have been no published studies on whether or not videotaping of consultations would be acceptable to a hospice population. Using a semi-structured questionnaire, we interviewed 31 patients who had agreed to have their consultation with a doctor videotaped. Although 30 (97%) did not regret having given permission and would 'definitely' or 'possibly' agree to another recording in the future, three (10%) felt that the procedure had been inadequately explained to them, six (19%) felt that they were 'possibly' or 'definitely' not given sufficient notice of the recording and one patient felt under pressure to agree to the recording. These findings suggest that if videotaping of consultations in the hospice setting is to be undertaken, more advanced notice than that usually given in general practice is required and strict safeguards should be in place to protect vulnerable patients. PMID- 11212469 TI - Determining the decision-making capacity of a patient who refused food and water. AB - A terminal patient expressed the wish to hasten her death and refused nutrition. The psychiatrist asked to render an opinion relevant to her competence employed questions in a semi-structured interview derived from a new instrument originally designed to determine competence to create 'Advance Directives'. Although the patient ultimately demonstrated her resolve by totally ceasing fluid intake, the complexity of the case--including the question of the stability of her choice- illustrates the need for specific patient safeguards. PMID- 11212470 TI - Can euthanasia be safely legalized? PMID- 11212471 TI - Interdisciplinary working: a Greek perspective. PMID- 11212472 TI - Describing the subjects in a study. PMID- 11212473 TI - Syringe driver drug compatibility database and patient information leaflets on the Internet. PMID- 11212474 TI - Use of a subcutaneous syringe driver in epidermolysis bullosa. PMID- 11212475 TI - The prevalence of episodic pain in cancer: a survey of hospice patients on admission. AB - Pain that varies with time, referred to here as episodic pain, is a commonly encountered but under-investigated clinical problem. Previous studies of cancer patients have found that a significant proportion of their pains are episodic. To establish the prevalence and characteristics of episodic pains in hospice in patients we assessed 245 consecutive admissions to four hospices in Yorkshire. The admitting doctor completed a questionnaire, detailing the characteristics of all pains experienced by the patient in the previous 24 h. Two hundred and forty two questionnaires were entered into the study. One hundred and thirty-two patients reported pain in the preceding 24 h, of these 93% had at least one episodic pain. In total, 228 pains were described, of which 211 were episodic with a wide variation in their temporal characteristics, intensities and limitation. One hundred and fifty-two episodic pains had a precipitating factor; movement and weight bearing being the most frequent precipitants. One hundred and sixty-eight episodic pains had a relieving factor, medication improving 54%. Ninety-five pains were related to the malignancy and 47 to concurrent illness. The study confirms that episodic pain is extremely common in cancer patients referred for in-patient hospice care and highlights the need for further evaluation of its management. PMID- 11212476 TI - Transplantation of fibula with vascular pedicle for fusion of ankle in leprotic drop-foot. AB - Devascularized bone grafts are pieces of dead bone and they simply serve as scaffolds for new bone to grow and fill the gap, taking a long time when they succeed in doing so. In contrast, vascularized grafts being living tissues have short healing time, great vitality and strong infection-resisting capacity. We report here the successful use of vascularized grafts of the lower end of fibula for fusing the ankle in five leprosy patients. PMID- 11212477 TI - Assessment of viability by normal mouse foot-pad and bacillary ATP bioluminescence assay in multibacillary cases treated with an MDT regimen using conventional as well as newer drugs like minocycline and ofloxacin. AB - The therapeutic effect of a drug regimen of conventional drugs as well as newer drugs like ofloxacin and minocycline in smear-positive multibacillary (MB) leprosy cases was assessed by mouse foot-pad and ATP bioluminiscence methods. Biopsies were taken before starting treatment and after one year of treatment. They were processed for viability assessment by normal mouse foot-pad inoculation and bacillary ATP assay techniques. The test regimen was quite effective in its anti-bacterial effect as it was found to result in loss of bacillary viability in all the cases, as assessed by both methods. PMID- 11212478 TI - Bacteriological study of pus isolates from neuropathic plantar ulcers associated with acute inflammatory phase. AB - In this retrospective study, sensitivity of organisms cultured from ulcers of leprosy patients without and with diabetes mellitus, diabetic patients without leprosy and patients with ulcers from other causes was examined. The profile of organisms grown from these groups of patients did not differ significantly. However, there was a high prevalence of organisms like Proteus, E. coli and Enterococcus in the ulcers of leprosy patients indicating faecal contamination of the ulcers. Co-trimaxazole and tetracycline were of little value in the treatment of these ulcers. We therefore recommend that in situations where there is no culture facility, the patients be started on a course of penicillin and gentamycin. If these antibiotics fail, it would be necessary to use more advanced antibiotics like norfloxacin, amikacin and ciprofloxacin. PMID- 11212480 TI - The use of pentoxifylline in the treatment of type 2 reactional episodes in leprosy. AB - It has been suggested that erythma nodosum leprosum (ENL) is associated with enhanced production of TNF-alpha resulting in increased inflammation of the skin and nerve function impairment. Thalidomide and steroids are the major drugs used in the treatment of ENL, but due to the serious problems associated with their use, alternative therapeutic interventions are being considered. In the present retrospective study, the authors report their clinical observations on the effect of pentoxifylline (PTX) in the treatment of ENL. Parameters, such as the clinical involution of reactional lesions, the regression of the inflammatory symptoms associated with the lesions, and the impact on the systemic symptoms common to ENL were assessed at regular intervals during PTX therapy. It was found that PTX therapy led to total elimination of systemic symptoms within the first week of treatment. This improvement was maintained until the end of the study (60 days of treatment). Moreover, the evolution of nodular lesions showed a 100% improvement within the first 14 days of treatment. However, by the 60th day, worsening of the lesions was noted in 20% of the cases. The impression is that PTX is well tolerated, and it may be used for improving patient's clinical condition during ENL reaction. Nevertheless, a randomized, double blind, controlled trial to compare the effects of the widely-accepted thalidomide and the yet untested pentoxifylline for treatment of type 2 reaction is still necessary. PMID- 11212479 TI - Intranasal administration of fusidic acid cream in leprosy. AB - The effect of local treatment of nostrils with fusidic acid cream was investigated in 30 previously untreated lepromatous leprosy patients. The cream was applied in the nostrils after flushing the nostrils with normal saline, twice a day for a period of four weeks. It was found that 20 mg/gm of sodium fusidate was effective in reducing the morphological index of the nose-blow smear to zero in two weeks in majority of the patients. No untoward side effect was seen in any of the patients. Such nasal treatment along with multidrug therapy may help in reducing the patient's level of infectiousness to their contacts, since the nose is recognized to be an important portal of exit of M. leprae. PMID- 11212481 TI - Status of long absentees among multibacillary leprosy patients admitted to a controlled clinical study. AB - Of 210 multibacillary leprosy patients who were admitted to a trial of two drug regimens, fifty-seven were excluded from efficacy analysis at 120 months for various reasons. Thirty-three of these patients were identified as long absentees. Efforts were made to contact these patients through letters and home visits to assess their clinical and bacteriological status and to find out the reasons for default. Twenty-one patients were thus retrieved. Only one patient was found to be having active disease requiring treatment; the rest were clinically inactive and bacteriologically negative. PMID- 11212482 TI - Multidrug therapy--the pathway for global leprosy elimination. AB - Introduction of dapsone therapy paved the way for better and more humanitarian way of dealing with the leprosy victims who, prior to 1943, were simply rejected and segregated from society. Emergence of dapsone-resistant M. leprae and mycobacterial persistence provoked our quest for another solution. More drugs were discovered for treatment of leprosy. But the real breakthrough was the recommendation of regimens of multidrug therapy (MDT) for the treatment of leprosy by the WHO Study Group on Chemotherapy of Leprosy in October 1981. Subsequent world wide development of leprosy control activities was phenomenal. The impact of MDT has led to the cure of over eight million leprosy sufferers and the saving of one million patients from becoming crippled. Leprosy prevalence has decreased by 80% in ten years. By the end of May 1999 the leprosy burden remained concentrated in only 12 countries of the world. These achievements are mainly attributed to the development and worldwide adoption of the MDT programme. PMID- 11212483 TI - Histoid leprosy--an unusual presentation. PMID- 11212484 TI - Lepromatous leprosy masquerading as molluscum contagiosum. PMID- 11212485 TI - Primary penile tuberculoid leprosy. PMID- 11212486 TI - [Problems in clinical use of immunomodulators in surgery]. PMID- 11212487 TI - [Trends in adjuvant pathogenetic therapy of infectious and autoimmune diseases]. PMID- 11212488 TI - [Autoimmune disorders in pregnant women with mixed urogenital infections. Interferon therapy in prophylaxis of obstetric and perinatal complications]. PMID- 11212489 TI - [Pathogenetic therapy in newborn from mothers with autoimmune disorders and mixed urogenital infections]. PMID- 11212490 TI - [Recombinant human erythropoietin--blood transfusion alternative]. PMID- 11212491 TI - [Modern concepts of stimulation of anti-infectious immunity with immunomodulators]. PMID- 11212492 TI - [Immunity in candidosis and immune correction]. PMID- 11212493 TI - [Cephalosporins of the third generation in therapy of children with severe infections]. PMID- 11212494 TI - [Therapeutic efficacy of the new drug Pharingal in acute inflammations of pharynx and tonsils in children]. PMID- 11212495 TI - [Clinical and laboratory efficacy of the novel difluoroquinolone Sparflo (sparfloxacin) in therapy of skin and soft tissue infections]. AB - Results of clinical trial of new difluoroquinolone--Sparflo (sparfloxacin, Dr. Reddy's Laboratories Ltd) are presented. Sparfloxacin was used in the treatment of 24 patients at the Department of Wounds and Wounds infections (11 patients) and at the Department of burn wounds (13 patients) of the A.V. Vishnevsky Institute of Surgery. After the treatment with sparfloxacin pathogen eradication was stated in 18 patients, eradication with superinfection--in 13 patients, persistence--in 3 patients. Thus bacteriological efficacy amounted to 87.5 per cent. Pharmacokinetic data demonstrates long-term sparfloxacin circulation in the organism of patients with burns--elimination half-life amounted to 20 hours. Overall after the sparfloxacin use the favourable clinical effect was stated in 100 per cent patients--18 patients (75%) had clinical cure and 6 (25%)--clinical improvement. The drug tolerance was good. It is concluded that clinical and laboratory investigation demonstrated high efficacy of sparfloxacin (Sparflo, Dr. Reddy's Laboratories Ltd) in the treatment of patients with skin and tissue wounds of different localization and genesis, complicated with infections. PMID- 11212496 TI - [Discussions on problems in chemotherapy at the VII National Russian Congress "Man and Drug"]. PMID- 11212497 TI - [Origin and evolution of mammalian sex chromosomes]. AB - Mammals present an XX/XY system of chromosomal sex determination, males being the heterogametic sex. Comparative studies of the gene content of sex chromosomes from the major groups of mammals reveal that most Y genes have X-linked homologues and that X and Y share homologous pseudoautosomal regions. These observations, together with the presence of the two homologous regions (pseudoautosomal regions) at the tips of the sex chromosomes, suggest that these chromosomes began as an ordinary pair of homologous autosomes. Birds present a ZW/ZZ system of chromosomal sex determination where females are the heterogametic sex. In this case, avian sex chromosomes are derived from different pairs of autosomes than mammals. The evolutionary pathway from the autosomal homomorphic departure to the present-day heteromorphic sex chromosomes in mammals includes suppression of X-Y recombination, differentiation of the nascent non-recombining regions, and progressive autosomal addition and attrition of the sex chromosomes. Recent results indicate that the event marking the beginning of the differentiation between the extant X and Y chromosomes occurred about 300 million years ago. PMID- 11212499 TI - Post-translational modifications of the regulatory subunits of cAMP-dependent protein kinases during G1/S progression. AB - During the G1/S transition of the cell cycle variations in the labelling by 8-N3 [32P]cAMP of the protein kinase A regulatory subunits RI and RII, used as a probe to monitor post-translational modifications that may regulate cAMP binding, were observed in synchronized HeLa cells. A decrease in 8-N3-[32P]cAMP labelling of RI, RII and RII phosphorylated by the catalytic subunit of PKA was correlated with the increased percentage of cells in phases G1. An increase in 8-N3 [32P]cAMP incorporated into the 54-kDa RII subunit during progression from G1 to S was correlated with an increase in intracellular cAMP. A transient increase in Mn-SOD activity was detected in cells arrested at the G1/S transition using two different techniques, suggesting that oxidative modulation of regulatory subunits by free radicals may modify cAMP binding sites during the cell cycle. Decreased photoaffinity labelling by 8-N3-[32P]cAMP of RI, RII and autophosphorylated RII subunits was found to be an inherent characteristic of PKA in the G1/S transition. PMID- 11212498 TI - [Transition metals and nitric oxide production in human endothelial cells]. AB - The bioavailability of endothelial nitric oxide (NO) is regulated by transition metals but their mechanisms of action on NO synthesis and degradation are not clearly understood. Using differential pulse amperometry and NO microelectrodes, local NO concentration was measured at the surface of cultured human umbilical vein endothelial cells (HUVECs) stimulated by histamine or thrombin in the presence of transition metal chelators. The agonist-activated NO release required both extracellular Ca2+ and transition metals. In the presence of 1 mM external Ca2+, a low concentration of EGTA (5 microM) inhibited by 40% the NO release from stimulated HUVECs. In the presence of extracellular L-arginine, the inhibitory effect of EGTA was even more marked and, in its absence, it was suppressed by adding exogenous superoxide dismutase. The decrease in NO release induced by the copper chelators, cuprizone and DETC, suggests that extracellular traces of Cu2+ could regulate NO availability. PMID- 11212500 TI - Noradrenergic modulation of tactile responses in rat cortex. Current source density and unit analyses. AB - This study describes the noradrenergic modulation of tactile afferent information in the sensorimotor cortex of urethane-anesthetized rats. Synaptic and spike responses to a mechanical stimulation of the hand palm were evaluated by means of current source-density analysis and unit activity recording in all cortical layers. Results showed that activation of the locus coeruleus decreased and shortened afferent synaptic excitation in supragranular, but not in deep layers. On the average, unit responses exhibited facilitated latency, moderately increased amplitude, enhanced postexcitatory inhibition and synchronization of responses across layers. The apparent paradox of this global phasic facilitation correlated with a decrease in input synaptic currents was discussed according to hypotheses which might explain its functional significance. PMID- 11212501 TI - [Skeletal configurations of cervical column during rest to motion transition: generalization that underlie the motor repertoire in rodents]. AB - During forward locomotion, guinea pigs adopted a posture which, although different, was as stereotyped as at rest. The whole extent of the vertebral column was extended, parallel to the earth-horizontal plane. This result supports the hypothesis that, in mammals, gaze and postural control by the central nervous system would be simplified by the adoption of a limited number of skeletal configurations. They would be optimized for energy saving, biomechanical efficacy and limitation of the number of degrees of freedom of the skeletal apparatus. Transition between rest and forward locomotion displayed two prominent characteristics: the head was stabilized versus space throughout the whole transition and the modifications of the skeletal geometry were confined to the median plane and to two major articular regions. Such an organization revealed a fourth characteristic of the guinea pig postural control: the skeletal configurations retained by evolution would ensure that smooth transitions take place between rest and the various activities of its motor repertoire. Finally, our purely descriptive data shed new light on the architecture of the neuronal network which underlies the vestibular control of gaze and posture. PMID- 11212502 TI - Productivity and carbon isotope discrimination in durum wheat organs under a Mediterranean climate. AB - For durum wheat, we promote the use of carbon isotope discrimination (delta) as an indirect selection criterion for transpiration efficiency and grain yield (GY), and we identify the most effective organ for characterising delta genotypic variation. A field experiment was conducted in the South of France on 144 accessions, with a drought period occurring from February to June. Harvest index (HI), GY and delta (delta L, flag leaf; delta A, awn, delta G grain) were measured. Significant positive genetic correlations were noted between delta and both GY and HI. A larger genotypic variation and a higher broad-sense heritability were noted for delta G compared to delta L and delta A. delta G correlated better with GY and HI than delta L and delta A, showing that delta G could provide a better assessment of genotypic behaviours under drought during grain filling. Moreover, the indirect selection based on delta G (even when evaluated with one replicate) appeared more efficient than the direct selection for grain yield. This result emphasised the potential value of grain carbon isotope discrimination as a criterion for grain yield improvement under stressed Mediterranean conditions. PMID- 11212504 TI - Evidence from DNA that the mysterious 'linh duong' (Pseudonovibos spiralis) is not a new bovid. AB - In 1993, several horns of an unknown mammal were collected in the south of Vietnam. Due to the unusual characteristics of its horns, the 'linh duong', as named by Vietnamese hunters, was quickly described as belonging to a new monospecific genus of bovid, i.e. Pseudonovibos spiralis Peter & Feiler, 1994. The taxonomic status of Pseudonovibos was a highly controversial subject, and it has been suggested that this enigmatic species may be related to three different groups of Bovidae: Antilopini (gazelles), Bovini (cattle, bisons, buffaloes), and Caprini sensu lato (goats, sheep and allies). To assess the phylogenetic relationships of the linh duong within the family Bovidae, two different DNA markers, the nuclear lactoferrin and the mitochondrial cytochrome b genes, were sequenced from bone samples of four trophies collected during 1925 in Indochina. Results show that the mysterious horns of linh duong belong to domestic cattle (Bos taurus). Thus, the linh duong is not a new mammal and the scientific name Pseudonovibos spiralis should be abandoned. PMID- 11212503 TI - [Humus functioning types in evergreen coniferous forests of the French Inner Alps]. AB - Three humus forms that are widespread in the Inner Alps, a dysmull below Pinus sylvestris, an oligomull below Abies alba and a mor below Pinus cembra, were studied by following mineral nitrogen production and uptake and by a characterization of the pedofauna. Due to the production and uptake of nitrogen, mainly as nitrates and also due to the dominance of Lumbricids versus Arthropods, the oligomull was the sole humus form that functioned as a mull. Nevertheless relatively weak mineral nitrogen production and the dominance of endogeic soil dwelling earthworms versus anecic earthworms demonstrated the moderate activity of this mull, which is representative of humus forms of old growth forests and cold climates. There was a discrepancy between the very low biological activity of the dysmull and its status of mull, while an observed bifunctioning between the different layers of this humus also differentiated it from the mor. PMID- 11212505 TI - The enigmatic new Indochinese bovid, Pseudonovibos spiralis: an extraordinary forgery. AB - In 1993, the discovery of several pairs of lyre-shaped horns with corrugations was recorded in Vietnam and regarded as evidence for a new, large bovid, later referred to as Pseudonovibos spiralis Peter & Feiler, 1994. Despite numerous field investigations made since 1994 in Vietnam and Cambodia, no new anatomical evidence has ever been found, except for two frontlets with their horn cores and horn sheaths. A new investigation has been carried out on six frontlets and based on a histological analysis of the keratin. It shows that the horns of P. spiralis are merely a skillful forgery made by carving and distorting ordinary cow horns. The horns of Pseudonovibos spiralis were, in some cases, positioned back onto the corresponding horn cores of domestic cow frontlets. The name Pseudonovibos spiralis is thus a junior synonym of Bos taurus, yet it remains valid and available. PMID- 11212506 TI - [Heterochronia via procrustean superimposition: application to the skulls of Homonidae primates]. AB - The procrustes superimposition method is well adapted to heterochronic studies in the field of evolutionary biology. 1) The procrustes method gives a precise and mathematical definition of two of the three heterochronic variables: size and shape. 2) It allows us to describe complex anatomical structures and thus to analyse the whole structure and not just to proceed trait by trait. 3) The approach is statistical and the different hypotheses and results may be statistically tested. 4) When applied to heterochronies the method allows us to test if there is a common shape change related to allometry. In the present study of three species of Hominoid primates, the procrustes superimposition reveals that various heterochronic processes are simultaneously present. Size-age-shape dissociations between species, already present in the first ontogenetic stage, are amplified with growth until adult stage. As compared with that of the chimpanzee, the growth of the gorilla skull is accelerated in terms of size-shape covariation and size alone. The growth of the human skull is neotenic as compared with that of the apes. PMID- 11212507 TI - [Lateralisation of the brain injury in female Wistar rats determines the immune and neurological status in offspring]. AB - The T-cell immune deficiency was found to be more obvious in offspring of rats with a right-side brain injury. The EMG pattern changed in accordance with the brain injury lateralisation in the muscles responsible for posture asymmetry. The offspring EMG disorders were more obvious in cases of a right-side brain injury in mothers. The right-side brain injury in mothers led to a higher negative emotionality and a diminished tentative-research behaviour in "open-field" tests in 30-day old offspring. PMID- 11212509 TI - [Cardiac pump function in rats of different ages during muscle training and hypokinesia]. PMID- 11212508 TI - [Comparative characteristics of myogenic responses in pial arterioles in normotensive and spontaneously hypertensive rats]. AB - In acute experiments on SHR and WKY rats, the pial arterioles' myogenic responses to a drop in systemic blood pressure (SBP) were studied. The SHR seem to be more capable of keeping the myogenic activity in low SBP. It might depend on structural changes in the vascular wall under these conditions wall in the SHR. PMID- 11212510 TI - [Effect of the body antiorthostatic posture on various circulation and respiration parameters in anesthetised cats]. AB - In anaesthetised cats, antiorthostatic posture of the body with an inclination angle of 30 degrees increased pressure in the vena cava superior and in jugular vein. The rest of the cardio-respiratory parameters were changed insignificantly. Physical and physiological mechanisms of the blood regional redistribution in alteration of the body gravitation orientation, are discussed. PMID- 11212511 TI - [Involvement of nitrogen oxide in the cerebral vasoconstriction during respiration with high pressure oxygen]. AB - High pressure oxygen evokes a cerebral vasoconstriction and diminishes cerebral blood flow with the aid of mechanisms which are not yet sufficiently studied. We were checking a hypothesis that the hyperbaric oxygen (HBO2) inactivates cerebral nitrogen oxide (NO), interrupts its basal relaxing effect, and evokes a vasoconstriction. In our experiments, HBO2 decreased cerebral blood flow depending on the pressure. Inhibiting the NO-synthase weakened basal vasorelaxation in breathing with atmosphere air and eliminated the vasoconstriction in exposure to the HBO2. Inactivation of O2 prevented the HBO2 induced vasoconstriction. The data obtained reveal that diminishing of cerebral blood flow in HBO is related to the NO inactivation and weakening of its basal vasorelaxing effect. Possible mechanisms of the NO inactivation may involve its reaction with oxygen and superoxide anion which lead to diminishing of the tissue NO concentration and weakening of its vasorelaxing effect. PMID- 11212512 TI - [Time correlation of the cardiac electric field on the body surface and depolarization sequences in the pigeon heart ventricle epicardium]. AB - Multifocal depolarisation of the pigeon ventricle's epicardium was revealed. A time inversion correlation was found between cardiac electrical field's positive and negative areas on the body surface and the multifocal depolarisation of the ventricle epicardium, during the period of initial ventricular activity. PMID- 11212514 TI - [Effect of cooling rate and intensity on the immune response and corticosterone blood level in rats]. AB - Changes in the rat antigen-induced immune activity were shown to depend on cooling depth: slight cooling activated the immune response whereas deep cooling inhibited it. Involvement of the skin cold receptors' dynamic activity in responses to rapid cooling attenuated the effect of cold exposure on the immune response as well as the corticosterone elevation in plasma. PMID- 11212513 TI - [Changes in the venous vessels capacitance in the cat forepaw in response to neurohumoral stimuli]. AB - The trend in changes of the cat forepaw vessels' capacity was found to practically not differ from the trend in shifts in the vena cava anterior basin's capacity: in both areas the capacity decreases in response to pressor neurogenic stimuli and decreases or increases under the effects of pressor and depressor humoral stimuli. The data obtained suggest that the trend in shifts of the vena cava anterior basin's capacity under the effects of pressor humoral stimuli mainly depends on the skin-muscular area's vessels, whereas the trend in shifts of the vena cava anterior basin's capacity under the effects of depressor humoral stimuli depends, apparently, on the shifts in the brain vessels' capacity function. PMID- 11212515 TI - [Functional activity and mechanical properties of blood leukocytes during heating in rats]. AB - Different phasic changes induced by exogenous hyperthermia in leukocytes correlated with the latter adhesion and resistance properties as well as osmotic factors. The changes seem to be related to unspecific reactions. Phagocytes' and migratory activity increased along with the time of heating exposure. Activation of protective reactions seems to be caused by humoral factors the amount of which increases in the blood along with the heating temperature. PMID- 11212516 TI - [Effect of cross-fostering on various physiological and behavioral features in Wistar and genetically cataleptic rats]. AB - In the GC rats reared by their natural mothers the plasma corticosterone concentration and open field locomotion were lower than in Wistar rats whereas the startle-reflex amplitude was higher. Cross-fostering did not affect the plasma corticosterone concentration or the startle-reflex amplitude. A negative correlation between these parameters was found. An open field test yielded lower results in Wistar rats reared by foster mothers belonging to the GC strain whereas the reverse cross-fostering did not affect the locomotion in GC rats. The data suggest that fostering affects the open field behaviour whereas cross fostering effects depend on the genotype of fostered litter. PMID- 11212517 TI - [Changes in the hormonal function of the hypophysis-adrenal system by administration of cortisol in 'fixed' phases of the postnatal ontogenesis in rats]. AB - Administration of cortisol on the 13th, 15th, and 17th days of postnatal ontogenesis was shown to exert a long-lasting modifying effect upon the hypophysis-adrenal system's (HAS) stress reactivity in the rat litter. The effect involved a longer duration of hormonal response to immobilisation stress: a longer-lasting elevation of the corticosterone level in the blood plasma suggesting a diminished sensitivity of the HAS to feed-back signal. In hippocampus, frontal cortex and hypothalamus of the experimental rats, a decrease in receptor binding of labeled corticosterone was revealed. PMID- 11212518 TI - [Delay inhibition of the active avoidance reflex and intertrial responses in rats in the shuttle box]. AB - A diminished probability of avoidance response in early phases of a warning signal was revealed with salient signals given after short intertrial intervals. The inhibition of the delay in avoidance response is due to an interaction of the safety state conditioning and the excitation elicited by onset of warning signal. PMID- 11212519 TI - [Electrophysiological pacemaking properties of the ureter peribladder area in cats and rats]. AB - The rhythm generated by the peribladder area was found to be slower than that generated by the basis perirenal pacemaker in cats and rats. The antiperistaltic waves' frequency of the peribladder area was the lowest within the range of all the recorded rhythms. PMID- 11212520 TI - [Hydrolases in the large intestine in rats with various experimental pathologies]. AB - In the colon mucous membrane, activity of a wide range of membrane and mainly intracellular enzymes was studied in the organism at different conditions. The data obtained suggest participation of digestive hydrolases in the colon not only on postdigestive processes but, in certain states of the organism, in digestive processes too. PMID- 11212522 TI - [Long-term potentiation of glutamatergic transmission and epileptiform activity induced by short-term episodes of anoxia in the CA1 field of the rat hippocampal slices]. PMID- 11212521 TI - [Effects of acetylcholine and histamine on leukocyte and neutrophil numbers in the endometrium of rats in various phases of the estrous cycle (by imprints)]. AB - Administration of the acetylcholine esterase antagonist aminostigmin increased the number of neutrophils in the estrus phase and the number of lymphocytes in the diestrus phase in rats. Histamine decreased both the neutrophils and lymphocytes at all stages of the estrus cycle in the uterus endometrium. PMID- 11212523 TI - [Effect of physical load on glucocorticoid binding in the fatty tissue cytosol]. PMID- 11212524 TI - [Effect of pH on the osmotic water flow stimulated by arginine vasopressin added to the solution at the bladder mucosa from the frog Rana temporaria]. PMID- 11212525 TI - [Lev Germanovich Leibson (1900-1996) (on his 100th birthday)]. PMID- 11212526 TI - [Centennial of the birth of Lev Germanovich Leibson]. PMID- 11212527 TI - [Hypothesis of the key coordinating role of adenylate cyclase signal mechanism and cAMP in regulatory effect of insulin superfamily peptides on fundamental cellular processes: cell growth, apoptosis, metabolism (Development of the L. G. Leibson's works)]. PMID- 11212528 TI - [STAT pathway of the intracellular signaling]. PMID- 11212529 TI - [Progress in studies on effect of leptin on the hypothalamus neurons]. PMID- 11212530 TI - [Hormonal regulation of metabolism and exotrophy in fishes. Polyfunctionality and polypotentiality]. PMID- 11212531 TI - [Internal symmetry of the mirror type in the primary structure of proteins: identification and the functional role]. PMID- 11212532 TI - [Ontogenesis of human islets of Langerhans. Review of light and electron microscopic data, immunohistochemical and functional data on fetal development of the endocrine pancreas]. PMID- 11212533 TI - [Binding of insulin-like growth factor I (IGF-1) in skeletal muscles of Lampetra fluviatilis dominates over insulin binding and increases during spawning migration]. PMID- 11212534 TI - [Primary structure of insulin from the Black Sea Scorpaena porcus]. PMID- 11212535 TI - [Adenylate cyclase signaling mechanism of the relaxin function]. PMID- 11212536 TI - [The role of mitogen-activated protein kinases in stimulation of the smooth muscle cell migration by urokinase]. PMID- 11212537 TI - [Tyrosine hydroxylase and/or aromatic L-amino acid decarboxylase-expressing neurons in the mediobasal hypothalamus of Wistar rats in ontogenesis: topographic interrelations and axonal projections to the medial eminence]. PMID- 11212538 TI - [Interaction of distant mechanoreceptor systems during presentation of the interspecies acoustic signals to intact and allatectomized male crickets Gryllus bimaculatus]. PMID- 11212539 TI - [Intestinal regulatory systems in invertebrates and their evolution in multicellular animals]. PMID- 11212540 TI - [Some elements of a portrait of Lev Germanovich Leibson]. PMID- 11212541 TI - [History of science in works of L. G. Leibson]. PMID- 11212542 TI - Contamination of animal feed and food from animal origin with mineral oil hydrocarbons. AB - Oils and fats used for the production of animal feed can become contaminated with mineral oil material originating from gas oils (C18-C35) or synthetic oils (poly alpha olefins, C25 to beyond C45). An important cause is assumed to be the discharge of waste oils, such as motor oil and hydraulic oils. Mineral oil material was analysed by on-line LC-GC-FID directly in the fat or in a raw extract from animal feed or foodstuffs. In Switzerland in summer/autumn 1999 concentrations in oils and fats for feed production were often found to be between 100 and 1000 mg/kg. In the feeds, the average concentration was around 100 mg/kg with values ranging up to a maximum of 1000 mg/kg; few samples were free of contamination. In animal body fat, the average concentration determined in summer 1999 was 25 mg/kg, with a maximum of 150 mg/kg, although in samples from December 1999, contamination was substantially lower. In the fat phase of eggs, the average concentration was 30 mg/kg, with a maximum of 80 mg/kg. Paraffin oil is used for feed production, which may account for part of the contamination problem (e.g. eggs). PMID- 11212543 TI - Development of an ELISA for sulfachlorpyridazine and investigation of matrix effects from different sample extraction procedures. AB - The development of an enzyme-linked immunosorbent assay (ELISA) for the detection of residues of sulfachlorpyridazine (SCP) is described for the first time. The assay is highly specific for SCP, is simple to perform and has a lower detection limit of 0.65 ng/ml in assay buffer. In potential application of the assay to detect residues of SCP at the 0.1 mg/kg level in eggs, milk, beef, lamb, pork, chicken, turkey, porcine kidney, porcine liver and pig feedstuffs is discussed with regard to the effects of sample extracts on the standard curves. The antibody exhibits a rare stability in assay buffers containing up to 30% methanol. It is concluded that the ELISA for SCP has the appropriate characteristics for development into a robust method for the detection of this sulphonamide in agri-food materials. PMID- 11212544 TI - A comparison of techniques for preparing fish fillet for ICP-AES multielemental analysis and the microwave digestion of whole fish. AB - Four catfish fillet homogenate treatments before multielemental metal analysis by simultaneous inductively coupled plasma/atomic emission spectroscopy were compared in triplicate. These treatments were: nitric acid wet-ashing by Parr bomb digestion; nitric acid wet-ashing by microwave digestion; tetramethylammonium hydroxide/nitric acid wet digestion; and dry-ashing. The tetramethylammonium hydroxide/nitric acid method was imprecise (coefficients of variation > 20%). The dry-ashing method was fast and sensitive but had low recoveries of 50% for spiked Pb and Al and was not as precise as the Parr bomb or microwave treatments. The Parr bomb method was the most precise method but was less sensitive than the microwave method which had nearly the same precision. The microwave method was then adapted to homogenates of small whole fish < or = 3 cm in length. The whole fish homogenate required more vigorous digestion conditions, and addition of more acid after the evaporative step because of the presence of less oxidizable and acid-soluble components than fillet. The whole fish homogenate was also more heterogeneous than catfish fillet. A quality assurance protocol to demonstrate homogenate uniformity is essential. The use of a non specialized microwave oven system allowed precise results for fillet and whole fish homogenates. PMID- 11212545 TI - Copper, zinc, tin and lead in canned evaporated milk, produced in Lithuania: the initial content and its change at storage. AB - The study has been carried out to elucidate what contents of heavy metals were typical for canned milk products--evaporated (TS 25.5-28.5%) sterilized milk and condensed sweetened milk, produced in Lithuania in the period 1983-1997. The influence of storage time upon the level of Sn, Pb, Cu and Zn in the products has also been determined. The results show that the most considerable changes occurred in Cu concentration, which gradually decreased from the maximum level in 1983-1985 (2.23 +/- 0.18 mg/kg) to the minimum level in the latest years (0.44 +/ 0.01 mg/kg). Such variation of copper content in canned milks can be closely connected with its changes in raw milk. Zinc content in canned milk products also was in good agreement with raw milk. The content of tin and lead in the canned products many times exceeded their concentration in raw milk and ranged from 28 +/- 2 and 0.093 +/- 0.005 to 114 +/- 4 and 0.29 +/- 0.01 mg/kg, respectively. It has been determined that the dependence of the concentration of tin and lead on the storage time of concentrated (or evaporated) sterilized milk is nearest to the parabolic, and in sweetened condensed milk to the exponential function, whereas the small increase of copper and zinc concentrations can be described by straight-line function. The functional dependence obtained enables one to predict the Sn and Pb level in canned evaporated milk products after storage and to foresee the safe initial concentration of these metals in freshly produced evaporated milk, assigned for storage. PMID- 11212546 TI - A survey of zearalenone in corn using Romer Mycosep 224 column and high performance liquid chromatography. AB - A survey of zearalenone (ZEA) in corn from various regions of Brazil was carried out by the analysis of 380 corn samples, of which 30 samples (7.8%) were found to be contaminated in the range of 46.7-719 micrograms/kg. ZEA was extracted with acetonitrile-water (84:16, v/v), cleaned-up on a Romer Mycosep 224 column, separated, detected and quantified by high performance liquid chromatography (HPLC). The in-house method characteristics of linearity, accuracy, precision, and detection limit were defined by means of recovery tests with spiked corn samples in the range of 35.8-716 micrograms/kg and the analysis of a naturally contaminated sample (n = 7). The mean recovery for ZEA was 99.4% and the relative standard deviation (RSD) varied from 0.7 to 26.6% in the range studied. The method has been shown to be accurate, quick and reliable for determination of zearalenone in corn. PMID- 11212547 TI - Absorption, distribution and excretion of aflatoxin-derived ammoniation products in lactating cows. AB - Peanut meal naturally contaminated with 3.5 mg/kg aflatoxin B1 (AFB1) was spiked with radiolabelled AFB1 (meal 14C-I0) and decontaminated by a small-scale copy of an industrial ammoniation process (meal 14C-I1). During the process 15% of the radioactivity was lost, whereas 90% of the remaining radiolabel could not be extracted from the meal. In the extractable part, AFB1 accounted for 10% of the radiolabel, consistent with a total AFB1 reduction of more than 99%. No degradation products were observed in the extracts. Four lactating cows were fed with a diet containing 15% of either meal 14C-I0 or 14C-I1 for 10 days. On day 9 of this treatment, respectively 23 and 67% of the radiolabel was excreted in the urine and faeces of cows fed meal 14C-I0, as compared with 2 and 101% in the case of cows fed meal 14C-I1. Milk contained respectively 1.35 (meal 14C-I0) and 0.25% (meal 14C-I1) of the radiolabel. Milk samples taken during the equilibrium stage contained respectively 5 and 0.5 ng/ml of AFB1-derived compounds. Aflatoxin M1 (AFM1) accounted for 50-80% of these compounds in the case of milk from cows fed 14C-I0, as compared with 6-20% in the case of 14C-I1. AFB1 to AFM1 carry-over rates for 14C-I0 or 14C-I1 were estimated to be respectively 0.5 and 5.9%. Only liver and kidney samples contained detectable levels of the radiolabel, being respectively 260 and 37 micrograms/kg for cows fed meal 14C-I0, and 10 and 3 micrograms/kg for those fed meal 14C-I1. In the latter case, more than 55% of the radiolabel in the liver could not be extracted, as compared with 90% in the group fed meal 14C-I1. A small part of the extractable radiolabel in the livers of cows fed meal 14C-I0 could be attributed to AFB1 and AFM1 (less than 1% of total radioactivity). In the case of the animals fed 14C-I1 there were indications for the presence of AFB1 and AFM1 (6% of total radioactivity). Decontamination of the highly contaminated (non-radiolabelled) peanut meal by two different industrial ammoniation processes, resulted in a similar reduction of the initial AFB1 levels of 3.5 mg/kg to 15 micrograms/kg. Feeding of diets containing 15% of the non treated and two treated peanut meals to cows for a period of 10 days, resulted in AFM1 levels in milk of respectively 2.1, 0.04 and 0.07 ng/ml. AFB1 to AFM1 carry over rates were calculated to be respectively 0.5, 2.0, and 3.6%. It is concluded that the efficient reduction of aflatoxin levels by ammoniation of contaminated peanut meal results in a strong reduction of aflatoxin-related residues in milk and meat of cows, most likely caused by a decreased bioavailability of the degradation products. PMID- 11212548 TI - Comparison of different extraction and clean-up procedures for the determination of fumonisins in maize and maize-based food products. AB - In order to optimize the analytical method for the determination of fumonisin B1 (FB1) and fumonisin B2 (FB2) in different maize products, five materials (maize flour, corn flakes, extruded maize, muffins and infant formula) were investigated under a variety of experimental conditions organized in a ruggedness test according to a factorial design. The influence of five factors (extraction solvent, extraction mode, volume of extraction solvent, test sample size and clean-up) on method performances was tested by four laboratories using spiked materials (0.5 microgram/g and 1.5 micrograms/g FB1 + FB2) and naturally contaminated materials (ca 1.5 micrograms/g with FB1 + FB2). The end determination step was performed by high-performance liquid chromatography analysis of the o-phthaldialdehyde derivatized extracts. The ruggedness test permitted identification of two critical factors in the analysis of fumonisins in the above products, namely 'extraction solvent' and 'clean-up procedure'. In particular, the use of acetonitrile (ACN)-water (1 + 1, v + v) as extraction solvent and immunoaffinity column for clean-up provided better recovery of fumonisins and chromatographic resolution as compared with methanol (MeOH)-water (3 + 1, v + v) and strong anion exchange (SAX), respectively. However, phase separation occurring after extraction with ACN-water may have given incorrect results. Based on the information obtained with the present study it was possible to develop a new method horizontally applicable to all the above mentioned maize based food matrices. PMID- 11212549 TI - Determination of bisphenol A in canned vegetables and fruit by high performance liquid chromatography. AB - A high performance liquid chromatography (HPLC) method was developed for the determination of bisphenol A (BPA) that had migrated into canned fruit and vegetables. BPA was extracted with acetonitrile from the solid portion of canned food, and with an OASIS HLB cartridge from the aqueous portion, respectively. Both extracts were cleaned up on a Florisil cartridge. The HPLC separation was carried out on a Wakosil II 3C18 RS column (4.6 x 150 mm) with acetonitrile-water (40:60, v/v) as a mobile phase with a flow rate of 0.8 ml/min. BPA was detectable by UV detector at 228 nm and determined with the similarity of chromatographic peak spectrum by multiwavelength detector (similarity index was 0.99 or above). The quantification limits were 10 ng/g for the solid portion and 5 ng/ml for the aqueous portion, respectively. BPA was mainly detected in the solid portion of canned food and found at the maximum level of 11 micrograms per can. To verify migration into the solid portion of canned food, a partitioning experiment was carried out. PMID- 11212550 TI - Investigation of migration from paper and board into food--development of methods for rapid testing. AB - A range of paper and board materials including carton board, corrugated board, napkins and paper towels intended for contact with food have been solvent extracted and substances present at the highest levels identified and quantified by GC/MS. Dibutyl phthalate, and diisopropylnaphthalene (DIPN) were selected to study migration to food and potential food simulants with the aim of developing a simple quick test that will give an equivalent or higher result. Tenax was found to be a suitable food simulant for dry foods and dry 'fatty foods' such as pastry and cake and was also found to be a suitable simulant for pizza base tested at higher temperatures for short contact times. The percentage migration values from corrugated and carton boards were generally in the range 15-40%, with the highest percentage being 49% for rice using conditions representing ambient storage. Quick tests were developed using Tenax under accelerated conditions of 4 h at 80 degrees C to cover room temperature storage with dry foods and fatty dry foods. These tests are suitable for compliance testing of paperboard samples if migration limits are applied in future legislation. Migration from tissues, napkins and paper towels was found to be at very low or not detectable levels, even when the levels of DIPN and DBP were significant. It is strongly suspected that this finding is due to a combination of short contact time, low grammage and the fact that the tissues absorb fat and moisture from foods, thus minimizing extraction from the paper. In all cases, the results from migration experiments into food and Tenax indicate that for the substances found at highest concentrations in the paper, currently accepted safety limits were not exceeded where they exist in EU legislation or in working documents applying to plastics. PMID- 11212552 TI - Esthetic analysis of the cervicofacial region. AB - For many patients the primary motivating factor for orthognathic surgery is improvement of their facial appearance. In order to achieve a satisfactory esthetic result and satisfy the patients' concerns, a systematic, thorough evaluation should be performed. Because the face is a complex anatomic unit, it is best to evaluate each distinct region of the face separately, taking care to relate the various parts to the whole. During this examination it is important that the patient be in natural head position with the lips in repose and the teeth lightly touching in a centric relationship. Direct measurements from the patient are always more accurate than those obtained from photographs or radiographs. The surgeon should keep in mind that the proper relationships between the various regions of the face are more important than specific angles or numbers. PMID- 11212551 TI - Volatile and non-volatile compounds in irradiated semi-rigid crystalline poly(ethylene terephthalate) polymers. AB - In this study two different semi-rigid crystalline and oriented polyethylene terephthalate materials were used and were irradiated at 25-kGy dose at room temperature by using a caesium137 radiator. Volatile and non-volatile compounds present in the irradiated materials were identified and quantified. The qualitative results obtained from HS/GC/TCD/FID analysis at room temperature showed volatiles could not be identified. The HS/GC/MSD analysis performed at 106 degrees C showed that the irradiation generated 668-742 micrograms/kg formic acid, 868-922 micrograms/kg acetic acid, 17-32 micrograms/kg 1,3-dioxolane, and 47-71 micrograms/kg 2-methyl-1, 3-dioxolane based on PET weight. The results obtained from the thermal desorption and GC/MSD performed at 200 degrees C showed that 10-12 mg/kg acetaldehyde, 479-975 micrograms/kg 1,3-dioxolane, and 6.6-11.2 mg/kg methyl-1, 3-dioxolane were detected after irradiation. The concentrations of the two dioxolanes found from thermal desorption were much higher than those observed in the HS, although formic and acetic acids were not detected. It is possible that the formic and acetic acids produced by irradiation underwent further reactions with ethylene glycol during thermal desorption to form the dioxolanes. The soluble solid extracted from various PET specimens before and after irradiation were in a range of 0.67-0.78%. PET cyclic trimer is the major component and is present at 0.41-0.50%, accounting for more than 50% of the percent total solid in PET. Statistically, irradiation did not increase the soluble solid and cyclic trimer. The overall results suggest that 25-kGy irradiation had a significant effect on increasing the volatile but not the non volatile compounds detected in the PET specimens. PMID- 11212553 TI - Considerations for esthetic facial surgery in the African-American patient. AB - Due to the diverse ethnic nature of most communities, the perception of beauty is not homogeneous. Beauty is a perception of good balance, symmetry, harmony, and features that are pleasing to the eye. It is not possible to quantitate beauty. Many attempts have been made to standardize what is and is not beautiful by establishing the ethnic norms. Surgeons commonly attempt to achieve these ideal norms, but they may not necessarily be considered beautiful by the individual patient. Therefore, it is imperative for the surgeon to completely understand the patients' goals for surgery, which may not fit the ideal norms published in studies for that specific ethnic community. It also has become essential for patients to be made aware of the limitations of surgery, especially if their goals are unrealistic, to avert future distress and medicolegal problems. Thus, what is "normal" is not necessarily beautiful, and perhaps it would be better to strive for what is considered beautiful to the individual patient, rather than normal. Within the African-American population, the concept of what is beautiful can be extremely diverse. The number of African Americans who seek cosmetic or esthetic facial surgery is limited. As the number of esthetic procedures performed in the African-American population increases, however, the more educated this population will become regarding these procedures, and the more comfortable the surgeon will become regarding his or her own sense of "African American beauty" and specific esthetic facial considerations for this population. It should be mentioned that as the number of African-American surgeons increases, their influence within the African-American population regarding the availability of esthetic procedures will also be felt. PMID- 11212554 TI - Alloplastic augmentation of the face. AB - The previously presented facial augmentation techniques can be used in conjunction with orthognathic procedures or may be performed as separate procedures. When performed properly, they can enhance facial esthetics and improve patient satisfaction. Alloplastic augmentation, when properly planned and performed, is predictable, stable, and generally accepted by the patient. PMID- 11212556 TI - The influence of maxillary osteotomy design on esthetic outcome. PMID- 11212555 TI - Soft tissue changes associated with orthognathic surgery. PMID- 11212557 TI - Techniques to control nasal features. PMID- 11212558 TI - Techniques to preserve or modify lip form during orthognathic surgery. PMID- 11212559 TI - Adjunctive cervicofacial liposuction. AB - Submental liposuction is an adjunctive surgical procedure that allows for the relatively predictable soft tissue recontouring of the cervicofacial region (Figs. 13 to 17). It may be performed independently as an outpatient procedure under intravenous sedation or as an adjunctive procedure during orthognathic surgery. Surgical complications are rare and are usually preventable with appropriate patient selection and surgical technique. Submental liposuction is a useful tool for enhancing the esthetic benefits of orthognathic surgery. PMID- 11212560 TI - Adjunctive rhinoplasty. PMID- 11212561 TI - Our magnificent obsession. PMID- 11212562 TI - Reflections on the astonishing 20th century. PMID- 11212564 TI - Periodontal prosthesis: a 50-year perspective. PMID- 11212563 TI - Discoveries of importance in restorative dentistry over the past 40 years. AB - The advancements in restorative dentistry over the past several decades have been impressive. It is now possible to prevent dental caries on a predictable basis. If prevention is not carried out in early life and teeth are lost, it is now possible to restore mutilated or missing teeth with high efficiency and effectiveness. The future for restorative dentistry is extremely bright and has never been better in its history. PMID- 11212565 TI - Children's dental health: the past is the present and the gateway to the future. PMID- 11212566 TI - Oral and maxillofacial surgery: a century of progress. PMID- 11212567 TI - Endodontics: controversial past, exciting present, incredible future. PMID- 11212568 TI - Evolution of orthodontic bracket design. PMID- 11212569 TI - Retrospective look at notable advances in periodontics in the 20th century. PMID- 11212570 TI - Alveolar ridge augmentation using mandibular block grafts: clinical update. PMID- 11212571 TI - Cosmetic and functional aspects of orthognathic surgery: a primer for dentists. PMID- 11212572 TI - Bone grafting the jaws in the 21st century: the use of platelet-rich plasma and bone morphogenetic protein. AB - The use of PRP and rhBMP-2 in facial skeletal reconstruction is supported by theoretical and practical human and animal data that represent exciting prospects for the 21st century. Although the use of PRP in conjunction with autogenous grafting of the maxillofacial complex increases the already impressive predictability of this technique, it is possible that improvement of the clinical use of rhBMP-2 may one day obviate the need for a donor site harvest of bone. PMID- 11212573 TI - Surgical removal of wisdom teeth and associated pathology. PMID- 11212574 TI - Cosmetic soft-tissue enhancement for dental implants. PMID- 11212575 TI - Evaluation and treatment of temporomandibular disorders: considerations for the general dentist. AB - Temporomandibular disorders are only one of a host of different conditions that may result in orofacial pain. Hence, due to this multifactorial etiology, it is imperative to adopt a multidisciplinary approach when treating these patients. Listed in Table 3 are some of the conditions that must be considered when a dentist faces the dilemma of orofacial pain of unknown etiology in clinical practice. PMID- 11212577 TI - A small-conductance Ca(2+)-activated K+ current and Cl- current in rat dental pulp cells. AB - We characterized a voltage-dependent ionic current in dental pulp cells on dental pulp slices using a nystatin perforated-patch recording configuration. The outward currents in dental pulp cells were inhibited by the following channel blockers: 1) Ca(2+)-free extracellular solution containing 10 mM Ba2+, 2) extracellular 400 nM apamin and 3) extracellular 300 nM 4,4' diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). On the other hand, 15 mM tetraethylammonium (TEA) did not inhibit the outward currents. The inhibitory effects of Ca(2+)-free extracellular solution, apamin and DIDS had voltage dependency. These results indicated that dental pulp cells expressed a small conductance Ca(2+)-activated K+ current (SK current) and a DIDS-sensitive Cl- current. The functional significance of these channels is discussed. PMID- 11212576 TI - Angiotensin II-induced depolarizations in hamster submandibular ganglion neurons. AB - Angiotensin II acts as an excitatory neurotransmitter of the sympathetic ganglia. In the parasympathetic neurons, however, angiotensin II (angio II)-induced responses have not been recorded. In this study, we investigated the effects of angio II in the hamster submandibular ganglion (SMG) neurons using a intracellular recording technique. Approximately 70% of these ganglion cells responded with persistent depolarization (3-6 mV, 5-9 min) at a concentration of 10 microM. The angio II-induced depolarizations were caused by the combination of an increase in Na+ conductance and a decrease in K+ conductance. An involvement of K+ channels such as M channels and SK channels in the electrogenesis mechanism was suggested by an inhibitory effect of Ba2+ ion on the component of the increased membrane input resistance during the angio II-induced depolarization. In addition, the angio II-induced depolarizations were mediated through angio II type I (AT1) receptors. Thus angio II is probably a neurotransmitter that increases their excitability in most of the neurons in parasympathetic ganglia. PMID- 11212578 TI - Effect of Er:YAG laser irradiation on acid resistance to bovine dentin in vitro. AB - Resin bond strength to Er:YAG laser irradiated dentin has been reported to be lower than that of unlased dentin. The reasons have been much discussed, but not clarified. One hypothetical cause has been discussed that lased dentin is acid resistant, therefore, the etching effect of acid conditions decreases. The purpose of this study was to evaluate the acid resistance of laser-irradiated dentin and compare it with the dissolved mineral of Er:YAG laser irradiated dentin and unlased dentin. This experiment was a pilot study to assess the etching effect of pre-conditioner for resin bonding to lased dentin. Bovine dentin was irradiated by Er:YAG laser and immersed in 0.1 M lactic buffer solution (pH 4.0). The dissolved Ca and P in the solution were then both measured. Dissolved Ca from lased dentin was not significantly different from that coming from unlased dentin (p > 0.05). The molar ratio of Ca/P did not differ significantly between lased and unlased dentin, either (p > 0.05). Under FE-SEM view before immersion, the dentin surface was covered with a smear layer in unlased dentin, but this layer was not clearly observed in lased dentin. These results suggested that the lased dentin had little or no resistance to lactic buffer solution. PMID- 11212579 TI - Influence of finishing on the electrochemical properties of dental alloys. AB - Dental alloy surface finishing procedures of may influence their electrochemical behavior, which is used to evaluate their corrosion resistance. We examined the polarization resistance and potentiodynamic polarization profile of the precious metal alloys, Type 4 gold alloy and silver-palladium alloy, and the base-metal alloys, nickel-chromium alloy, cobalt-chromium alloy, and CP-titanium. Three types of finishing procedure were examined: mirror-finishing using 0.05 micron alumina particles, polishing using #600 abrasive paper and sandblasting. Dissolution of the alloy elements in 0.9% NaCl solution was also measured and compared with the electrochemical evaluation. The corrosion resistance of the dental alloys was found to relate to finishing as follows: The polarization resistance and potentiodynamic polarization behavior revealed that the corrosion resistance improved in the order of sandblasting, #600-abrasive-paper polishing, and mirror-finishing. While the corrosion potential, critical current density and passive current density varied depending on the type of finishing, the transpassive potential remained unchanged. The influence of finishing on the corrosion resistance of precious-metal alloys was less significant than on that of base-metal alloys. A mirror-finishing specimen was recommended for use in evaluation of the corrosion resistance of various dental alloys. PMID- 11212580 TI - Influence on myoelectric discharges of anteroposterior displacement of the mandibular position near the tapping point. AB - The purpose of this study was to examine the influence that the anteroposterior mandibular displacement near the tapping point exerts on the myoelectric activity of masseter and temporal muscles at a specific occluding force and to clarify the possibility of judging the mandibular position by measuring the amount of myoelectric discharge. Eight dentulous subjects were selected for the study. Surface electrodes were placed over the anterior, middle and posterior regions of the masseter muscle and over the anterior, middle and posterior bundles of the temporal muscle. Independently of the measurement region, the changes in the masseter and temporal muscle myoelectric activity which accompanied the anteroposterior mandibular displacement, were low. Moreover, when the mandible was displaced anteroposteriorly, the total amount of the myoelectrical discharge from all the recorded places, as well as the amounts of myoelectrical discharge over the middle part of the masseter muscle and the anterior bundle of the temporal muscle reached their lowest values in those mandibular positions which included the tapping point in less than half of the subjects. Therefore, this study indicates that the possibility of judging anteroposterior mandibular displacement by masseter and temporal muscle electromyography is quite low. PMID- 11212581 TI - Surgical simulation of Class III edentulous patient using a 3D craniofacial model: report of a case. AB - A case of edentulous prognathism in a 46-year-old Japanese male is presented. We described the outcome of the patient who underwent simultaneous sagittal splitting ramus osteotomy of the edentulous mandible, interpositional bone graft of severely atrophic edentulous jaws, and delayed placement of titanium implants for reconstruction. We highly recommend performing a surgical simulation using a craniofacial model of the patient's anatomy created using CT image data. The procedure provides almost ideal maxillary and mandibular contours. PMID- 11212582 TI - Significance of detection of Porphyromonas gingivalis, Bacteroides forsythus and Treponema denticola in periodontal pockets. AB - The relationship between the detection of Porphyromonas gingivalis, Bacteroides forsythus and Treponema denticola in subgingival plaque samples of periodontal pockets and periodontal status was evaluated using the polymerase chain reaction (PCR). A total of 165 sites in 60 periodontitis patients were examined, and the relationships between the detection of each of the three bacterial species and the pocket depth and bleeding on probing (BOP) were analyzed. The detection ratios of P. gingivalis, B. forsythus, and T. denticola in samples from adult periodontitis lesions were 75.5%, 69.8%, and 72.6%, respectively. It was found that all sites where all three microorganisms were detected were BOP positive and had greater pocket depths than those where only one or two species were found. The detection rate of B. forsythus and T. denticola decreased with age in the sites in which PD was less than 4 mm. The present study indicates that detection of a mixed infection by P. gingivalis, B. forsythus, and T. denticola strongly correlated with adult periodontitis. PMID- 11212583 TI - Histological study of masseter muscle in a mouse muscular dystrophy model (mdx mouse). AB - Histological changes in the masseter muscle were observed over time in mdx mice, a muscular dystrophy model. It was found that marked necrosis occurs about the time of weaning at around 4 weeks of age; then the tissue actively regenerates at 8 weeks and stabilizes as regenerated muscle with centronuclei at 15 weeks old. This study examined the centronucleus in regenerated muscle. The process from necrosis to regeneration in muscle fibers occurs a little later in the masseter muscle than in other limbic muscles. Regenerated muscles observed around 15 weeks after birth showed a moth-eaten appearance. Transmission Electron Microscope (TEM) observation of transverse sections of muscle fibers revealed that myofibrils surrounded lost regions in the area showing a moth-eaten appearance. Thus, some defensive mechanism may affect the ability of muscle fibers to maintain a function close to normal in mdx mice even though the muscle fibers develop muscular dystrophy. The function of the masseter muscle drastically changes from sucking to mastication behavior at around 4 weeks, and this was considered to influence the morphological changes in the muscle tissue. The moth eaten appearance seen at 15 weeks may represent an appropriate myofibril reconstruction preventing invasion of the lost regions. PMID- 11212585 TI - Survey of dental treatments for pediatric patients referred to the pediatric dental clinic of a dental school hospital. AB - This survey was conducted to clarify which dental treatments in children are regarded as difficult by general dentistry practitioners. The subjects were 615 children who first visited Tokyo Dental College Chiba Hospital from January 1995 to August 1999 with reference letters. There were 615 children in the study; 571 (92.8%) came from Chiba City where our hospital is located and the 11 regions surrounding Chiba City. The prime reasons for referral in the order of frequency were treatments of dental caries, malalignment/malocclusion, traumatized teeth, supernumerary teeth, retarded eruption/impacted teeth, abnormal direction of erupted teeth, congenitally missing teeth, prolonged retention of deciduous teeth, and abnormal frenulum. Patients with dental caries or traumatized teeth in the deciduous dentition period and those with malalignment/malocclusion, supernumerary teeth, or retarded eruption/impacted teeth in the mixed dentition period were often referred to medical organizations specializing in pediatric dentistry because of the difficulties in controlling the patients' behavior and in providing adequate treatment. The information about pediatric dental treatments considered difficult by general dentists revealed by this survey appears to be useful and needs to be incorporated in the programs for clinical training of undergraduate students and education of postgraduate students. PMID- 11212584 TI - Adsorption of oral bacteria to porous type calcium carbonate. AB - The purpose of this study was to investigate the adsorption of [3H]-thymidine labeled oral microorganisms to porous type calcium carbonate (PCC) beads in a buffer containing human parotid saliva and to PCC combined chewing gum sheets. Adsorption rates of Streptococcus sobrinus B13 and 6715, Streptococcus mutans MT8148R and Actinomyces naeslundii T14V with PCC were significantly higher than those with calcium carbonate (CC) beads (p < 0.01). Adsorption rates of S. sobrinus, S. mutans and A. naeslundii with PCC combined chewing gum were significantly higher than those with CC combined chewing gum (p < 0.01). The present results suggested that the chewing gum containing PCC may be able to exclude oral bacteria, including cariogenic and periodontopathic bacteria, for prevention of dental caries and periodontal disease. PMID- 11212586 TI - Differences in TNF-alpha producing activity from murine peritoneal macrophages induced by lipopolysaccharides of Prevotella heparinolytica and Porphyromonas gingivalis. AB - We compared the effects of LPSs from P. gingivalis and P. heparinolytica on the induction of tumor necrosis factor-alpha (TNF-alpha) production by murine peritoneal macrophages. The lipopolysaccharide (LPS) preparation from P. gingivalis showed a typical ladder pattern in SDS-PAGE, whereas that from P. heparinolytica formed several stained bands without a ladder pattern. When the macrophages from C3H/HeJ mice were incubated with P. gingivalis LPS, the level of TNF-alpha released in the culture supernatants was significantly higher than that with P. heparinolytica. All tested reagents except genistein strongly inhibited the production of TNF-alpha by the macrophages after induction by either LPS. These results suggested the following possibilities, i) the induction level of TNF-alpha by P. heparinolytica is similar to that of Salmonella minnesota, ii) tyrosine phosphorylation is not the only pathway for the TNF-alpha production induced by these LPSs, iii) different regulatory mechanisms are involved in TNF alpha production in P. gingivalis LPS stimulated and P. heparinolytica LPS stimulated cells. PMID- 11212587 TI - Contrast-enhanced conventional CT in patients after surgery for malignant tumors: evaluation of the optimal method of the administration of the contrast medium. AB - Patients after ablative surgery for malignant tumors require computed tomography (CT) examination of a wide area on the head and neck to follow-up for recurrence and lymph metastasis. The aim of this study was to determine a more effective method for the infusion of the contrast medium into post-operative patients undergoing conventional CT, based on the relationship between the method of administering the contrast medium and the contrast-enhancing effect in the internal jugular vein. First eleven images were selected from the existing contrast-enhanced and plain CT images in a manner such that the CT values of the internal jugular vein were distributed evenly in a range of 50-180. Seven experienced observers evaluated the contrast-enhancing effect of each image set at a window value of 40 and window widths of 120, 200, and 280. Secondly, the CT values of the right internal jugular vein were measured in a total of 10 CT images from the thyroid to maxillary sinus level from each of 60 post-operative patients. The injection needles and contrast-enhancing techniques used in the 60 patients were drip infusion using an 18G injection needle in 20, drip infusion using a 21G injection needle with bolus intravenous injection immediately before scanning in 20, and drip infusion using a 23G injection needle with bolus intravenous injection immediately before scanning in 20. A CT value of 100 or above, preferably 120 or above, in the internal jugular vein was needed for the contrast-enhancing effect of a CT image to be judged as clinically significant. Our results found that, when a conventional CT was used in patients after surgery for malignant tumors, drip infusion using a 21G or 23G injection needle should be combined with bolus injections immediately before the beginning of scanning, and at the glottis or submandibular gland level during the scanning. A sufficient contrast-enhancing effect can also be obtained by drip infusion using an 18G injection needle without bolus injection. PMID- 11212588 TI - Antidepressant use during pregnancy. PMID- 11212589 TI - Antidepressants as analgesics: an introduction. PMID- 11212590 TI - Antidepressants as analgesics: an overview of central and peripheral mechanisms of action. AB - Antidepressants, given systemically, are widely used for the treatment of various chronic and neuropathic pain conditions in humans. In animal studies, antidepressants exhibit analgesic properties in nociceptive, inflammatory and neuropathic test systems, with outcomes depending on the specific agent, the particular test, the route of administration and the treatment method used. Although early studies focused on central (i.e., supraspinal, spinal) actions, more recent studies have demonstrated a local peripheral analgesic effect of antidepressants. These peripheral actions raise the possibility that topical formulations of antidepressants may be a useful alternative drug delivery system for analgesia. Antidepressants exhibit a number of pharmacological actions: they block reuptake of noradrenaline and 5-hydroxytryptamine, have direct and indirect actions on opioid receptors, inhibit histamine, cholinergic, 5-hydroxytryptamine and N-methyl-D-aspartate receptors, inhibit ion channel activity, and block adenosine uptake. The involvement of these mechanisms in both central and peripheral analgesia produced by antidepressants is considered. Data illustrating the preclinical peripheral analgesic actions of antidepressants are presented, as are some aspects of the mechanisms by which these actions occur. PMID- 11212592 TI - Putative mechanisms of action of antidepressant drugs in affective and anxiety disorders and pain. AB - An enhancement of neurotransmission of serotonin (5-HT), noradrenaline, or both, underlies the antidepressant response associated with most agents presently available to treat major depression. With respect to the 5-HT system, antidepressant drugs exert immediate effects on some neuronal elements controlling overall transmission, but it is the gradual changes in neuronal responses to such treatments that are ultimately responsible for producing their therapeutic benefits. In major depression, an increase in 5-HT1A transmission is thought to be a crucial determinant of the antidepressant response, whereas an enhancement of 5-HT2 transmission in the orbitofrontal cortex may mediate the therapeutic effect of 5-HT reuptake inhibitors in obsessive-compulsive disorder (OCD). The doses of medication and the durations of treatment necessary to obtain these alterations in 5-HT transmission in various brain structures of laboratory animals are fully consistent with the conditions in the clinic necessary to attenuate symptoms in depression and OCD. It is also possible that the relief of chronic pain produced by some antidepressants may be mediated, in part, by the blockade of peripheral 5-HT2A receptors. These observations emphasize the notion that the 5-HT system is endowed with different adaptive properties in various parts of the body, which, in addition to the multiplicity of 5-HT receptors, makes this chemospecific network important in many disorders. PMID- 11212591 TI - Antidepressants as analgesics: a review of randomized controlled trials. AB - This review provides an overview of 59 randomized placebo-controlled trials that examined the analgesic effect of antidepressants. To summarize, there is significant evidence that the tricyclic group of antidepressants is analgesic and that trazodone is not; the data regarding selective serotonin reuptake inhibitors are conflicting. To date, there are no randomized controlled trials examining the potential analgesic action of nefazodone or venlafaxine, but on the basis of initial clinical reports and its structural similarity to other analgesics, venlafaxine shows promise as an analgesic. PMID- 11212593 TI - Abrupt discontinuation of psychotropic drugs during pregnancy: fear of teratogenic risk and impact of counselling. AB - OBJECTIVE: To assess the consequences to mother and baby of abruptly discontinuing antidepressant or benzodiazepine medication during pregnancy and to assess the impact of our counselling. PARTICIPANTS: All women who consulted the Motherisk Program between November 1996 and December 1997 and who stopped taking antidepressant or benzodiazepine medication when pregnancy was confirmed agreed to participate in the study. DESIGN AND INTERVENTIONS: Subjects were interviewed, received counselling, and completed a questionnaire 1 month after their initial call and after the birth of their baby. RESULTS: Of 36 women who completed the study, 34 discontinued their medication abruptly for fear of harming the fetus, 28 on the advice of their physician; 26 (70.3%) women reported physical and psychological adverse effects, 11 reported psychological effects only, and 11 reported suicidal ideation (4 were admitted to hospital). After counselling, 22 of 36 (61.1%) women resumed taking their medication, and 4 found that they no longer required it. One woman had a therapeutic abortion and 2 experienced spontaneous abortions; there were therefore 35 healthy babies (including 2 sets of twins) born to 33 women; 14 of 21 mothers breast-fed their babies while taking their psychotropic medication, with no adverse effects reported. CONCLUSIONS: When assessing the risks and benefits of taking psychotropic medication during pregnancy, women and their physicians should be aware that the abrupt discontinuation of psychotropic drugs can lead to serious adverse effects. Counselling is effective in reassuring women to adhere to therapy. PMID- 11212594 TI - Does sex influence the relation between symptoms and neurocognitive functions in schizophrenia? AB - OBJECTIVE: A secondary analysis of our data to investigate if sex influences the specificity of the relationship between each of the 3 clinical syndromes (i.e., reality distortion, disorganization and psychomotor poverty) in schizophrenia and the neurocognitive functions that are thought to represent regional brain functions. PATIENTS AND DESIGN: Fifty-seven male and 30 female patients with a DSM-III-R diagnosis of schizophrenia were rated on the Scale for Assessment of Negative Symptoms and the Scale for Assessment of Positive Symptoms to derive scores for psychomotor poverty, disorganization, and reality distortion syndromes. All subjects completed a battery of neuropsychological tests purported to assess functioning of left temporal, right temporal, left basal frontal, right basal frontal, and dorsolateral prefrontal cortex. RESULTS: Correlation coefficients between syndrome scores and neuropsychological measures showed only word fluency (left frontal functioning) to have a statistically significant association with psychomotor poverty in women (p < 0.01). This relation was specific to psychomotor poverty syndrome. No relations between neurocognitive measures and symptoms were seen in men. CONCLUSIONS: The lack of specific relations between symptom dimensions in schizophrenia may be influenced by the fact that the neuronal circuitry associated with particular symptom dimensions may differ in men and women. PMID- 11212595 TI - Quetiapine and obsessive-compulsive symptoms (OCS): case report and review of atypical antipsychotic-induced OCS. AB - The atypical antipsychotics have advanced the treatment of schizophrenia and have proved to be effective agents in treating other disorders with or without psychotic features. We review the literature concerning an increasingly reported and interesting adverse effect, atypical antipsychotic-induced obsessive compulsive symptoms (OCS). The first known report of quetiapine exacerbating OCS in a 43-year-old man with obsessive-compulsive disorder (OCD), trichotillomania, delusional disorder and bipolar II disorder is presented. Mechanisms, including 5 HT2A and 5-HT2C antagonism, serotonergic regulation of dopamine systems and putative dopaminergic subtypes of OCS and OCD, are discussed. Given the paradoxical efficacy of the atypical antipsychotics in pure OCD, the neurobiology and comorbidity of OCD and schizophrenia, as well as the increasing use of atypical antipsychotics, a cautious and rational pharmacotherapeutic treatment approach is recommended. PMID- 11212596 TI - Hallucinations and the cerebral hemispheres. PMID- 11212597 TI - What is the best approach to treating interferon-induced depression in people with multiple sclerosis? PMID- 11212598 TI - Distribution and characterization of proliferative cells in the rat mandibular condyle during growth. AB - Distribution of proliferative cells and localization of types I and II collagen were examined in the rat mandibular condylar cartilage of 36 long-Evans/Turku strain rats during normal postnatal growth using an immunohistochemical method combined with histomorphometry. There were considerable differences in the thickness of the proliferative cell layer in the condylar head, with most mitoses occurring in the postero-superior area. It was found that the extracellular matrix of the proliferative cells does not stain for type II collagen in 20-day old and older rats, and that besides the subchondral bone, the strongest intensity for type I collagen stain was always localized in the articular surface of the condylar head. Statistically significant overlapping of the proliferative cell layer and the one secreting type II collagen occurred during the earlier stages of development, particularly in the postero-superior area of the condylar head. As type II collagen is considered to be a marker for identification of typical cartilage cells, the findings indicate that, in addition to undifferentiated cells, a portion of the proliferative cells can be characterized as chondroblasts during the early postnatal period in rats, but not in the later stages of development. The developmental phase of the condylar cartilage should therefore be taken into consideration when the effect of various biomechanical and humoral/hormonal factors on growth of the condylar cartilage is examined. PMID- 11212599 TI - Proliferative response of cells of the dentogingival junction to mechanical stimulation. AB - The aim of this research was to study the proliferative response of junctional epithelium (JE) and gingival connective tissue (GCT) to mechanical stimulation in vivo with regard to the potential occurrence of apical migration of JE and loss of GCT attachment during orthodontic tooth movement. Elastic bands were inserted between the maxillary first and second molars of male rats aged 8 weeks, which were pulse-labelled with 3H-thymidine and subsequently killed in groups, together with labelled control animals (a total of 98 rats) after periods of 1-168 hours. Autoradiographs were prepared from plastic mesiodistal sections, and parameters of cell proliferation for JE and GCT of the papilla between the second and third molars were determined. Although the distance between the apical limit of JE and the most coronal periodontal ligament (PDL) fibres decreased on the pressure and increased on the tension sides of mechanically stimulated animals, the total cross-sectional area of JE remained unchanged compared with controls. In the basal and suprabasal layers of JE, cell proliferation was reduced on the pressure side and showed no change on the tension side. In the apical JE compartments on both sides, mechanical stressing resulted in lower proliferative activity. Cell proliferation in GCT adjacent to JE in stimulated animals did not differ from the corresponding controls. JE rapidly adapted to mechanical stimulation by means of differential local adjustments of cell proliferation without an occurrence of apical migration or hyperplasia. GCT cells in the vicinity of JE maintained their steady-state proliferative activity. These results do not support the concept that orthodontic tooth movement might per se have detrimental effects on the stability of the dentogingival junction. PMID- 11212600 TI - Computer tomographic and radiographic changes in the temporomandibular joints of two young adults with occlusal asymmetry, treated with the Herbst appliance. AB - Two young patients, one female and one male, with asymmetric occlusal deviation and extreme Angle Class II division 1 malocclusions were treated with the Herbst appliance after cessation of endochondral growth (union of the radius epiphysis). During treatment, computer tomographic (CT) scanning and orthopantomograms of the temporomandibular joints (TMJs) revealed, as a result of bone modelling, asymmetrical new bone formation as a double contour on the distocranial part of the condyles. The treatment results were followed for more than 2 years and the new bone was found to be stable. PMID- 11212601 TI - Root resorption after orthodontic treatment in high- and low-risk patients: analysis of allergy as a possible predisposing factor. AB - The development of excessive root resorption during orthodontic tooth movement is an adverse side-effect, which is of great concern. The aim of this investigation was to analyse factors that might be associated with orthodontically induced root resorption. After buccal movement of maxillary premolars in 96 adolescents, the experimental teeth were extracted and subjected to histological analysis and measurement of resorbed root area. Fifty individuals, 18 boys and 32 girls, mean age 13.4 years, were selected and divided into two equal groups: the high-risk group based on measurements of the most severe root resorptions, and the low-risk group on measurements of mild or no root resorptions. After a preliminary screening of possible risk factors regarding root resorption, i.e. root morphology, gingivitis, allergy, nail-biting, medication, etc., only those subjects with allergy showed an increased risk of root resorption, but this was not statistically significant. PMID- 11212602 TI - A radiographic comparison of apical root resorption after orthodontic treatment with a standard edgewise and a straight-wire edgewise technique. AB - The purpose of this study was to compare the severity of apical root resorption occurring in patients treated with a standard edgewise and a straight-wire edgewise technique, and to assess the influence of known risk factors on root resorption incident to orthodontic treatment. The sample consisted of 80 patients with Angle Class II division 1 malocclusions, treated with extraction of at least two maxillary first premolars. Variables recorded for each patient included gender, age, ANB angle, overjet, overbite, trauma, habits, invagination, agenesis, tooth shedding, treatment duration, use of Class II elastics, body build, general factors, impacted canines, and root form deviation. Forty patients were treated with a standard edgewise and 40 with a straight-wire edgewise technique, both with 0.018-inch slot brackets. Crown and root lengths of the maxillary incisors were measured on pre- and post-treatment periapical radiographs corrected for image distortion. Percentage of root shortening and root length loss in millimetres were then calculated. There was significantly more apical root resorption (P < 0.05) of both central incisors in the standard than in the straight-wire edgewise group. No significant difference was found for the lateral incisors. Root shortening of the lateral incisors was significantly associated with age, agenesis, duration of contraction period (distalization of incisors), and invagination, while root shortening of the central incisors was related to treatment group and trauma. PMID- 11212603 TI - Dental follicle cell-conditioned medium enhances the formation of osteoclast-like multinucleated cells. AB - An influx of mononuclear cells and the subsequent increase of osteoclasts around tooth germs suggests that the dental follicle (DF) regulates or influences bone resorption required for tooth eruption. In order to study the effects of DF cell products on osteoclast formation during tooth eruption, a conditioned medium (CM) was created in which DF cells were added to mouse bone marrow cultures. Tartrate resistant acid phosphatase (TRAP)-positive osteoclast-like multinucleated cells were formed in the presence of 10 nM 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. The CM, dose-dependently, stimulated the formation of TRAP-positive cells in the presence of 1,25(OH)2D3 for 14 days culture. The number of these cells decreased due to degradation in the control culture. A semi-solid methylcellulose assay in the presence of CM showed little expression of colony-stimulating activity. These results suggest that the DF cells of a developing tooth produce factor(s) that enhance osteoclast formation and bone resorption necessary for tooth eruption. PMID- 11212604 TI - A comparative analysis of distal maxillary molar movement produced by a new lingual intra-arch Ni-Ti coil appliance and a magnetic appliance. AB - The aim of the study was to evaluate cephalometrically the dental and skeletal treatment effects of a new lingual intra-arch Ni-Ti coil appliance for molar distalization and to compare these with those of an established intra-arch appliance that uses repelling magnets for distal molar movement. Two groups of 21 adolescents, all girls, participated in this retrospective study. One group was treated with the new lingual Ni-Ti coil appliance for 6.5 months and the other with the magnetic appliance for 5.8 months. The treatment effects were analysed by measurements on lateral head radiographs at the start of treatment and after the molar distalization was completed. The mean amount of distal molar movement was 2.5 mm (SD 0.69) in the lingual coil group and 2.6 mm (SD 0.51) in the magnet group. A significantly higher degree of distal molar tipping was found in the magnet group, -8.8 degrees, compared with -2.2 degrees for the lingual coil group. Due to anchorage loss, the maxillary incisors moved forwards, and the overjet was increased by an average of 1.2 mm in the lingual coil group and 1.7 mm in the magnet group. The results indicate that the new lingual Ni-Ti coil appliance was better choice than the magnet appliance for distal bodily movement of maxillary molars. The benefits of the new Ni-Ti appliance were due to the design preventing molar tipping and its single activation. PMID- 11212606 TI - Open bite: stability after bimaxillary surgery--2-year treatment outcomes in 58 patients. AB - Stability after bimaxillary surgery to correct open bite malocclusion and mandibular retrognathism was evaluated on lateral cephalograms before surgery, 8 weeks post-operatively, and after 2 years. The 58 consecutive patients were treated to a normal occlusion and good facial aesthetics. Treatment included the orthodontic alignment of teeth by maxillary and mandibular fixed appliances, Le Fort I osteotomy, and bilateral sagittal split ramus osteotomy. Twenty-six patients also had a genioplasty. Intra-osseous wires or bicortical screws were used for fixation. Twenty-three patients had maxillo-mandibular fixation (MMF) for 8 weeks or more, six for 4-7 weeks, 14 for 1-3 weeks, and 15 had no fixation. At follow-up 2 years later, the maxilla remained unchanged and the mandible had rotated on average 1.4 degrees posteriorly. Seventeen patients had an open bite. Among them, eight patients had undergone segmental osteotomies. The relapse was mainly due to incisor proclination. The most stabile overbite was found in the group with no MMF after surgery. PMID- 11212605 TI - The congenitally missing upper lateral incisor. A retrospective study of orthodontic space closure versus restorative treatment. AB - Orthodontic treatment for patients with uni- or bilateral congenitally missing lateral incisors is a challenge to effective treatment planning. The two major alternatives, orthodontic space closure or space opening for prosthetic replacements, can both compromise aesthetics, periodontal health, and function. The aim of this retrospective study was to examine treated patients who had congenitally missing lateral incisors and to compare their opinion of the aesthetic result with the dentists' opinions of occlusal function and periodontal health. In this sample, 50 patients were identified. Thirty had been treated with orthodontic space closure, and 20 by space opening and a prosthesis (porcelain bonded to gold and resin bonded bridges). The patient's opinion of the aesthetic result was evaluated using the Eastman Esthetic Index questionnaire and during a structured interview. The functional status, dental contact patterns, periodontal condition, and quality of the prosthetic replacement was evaluated. In general, subjects treated with orthodontic space closure were more satisfied with the appearance of their teeth than those who had a prosthesis. No significant differences in the prevalence of signs and symptoms of temporomandibular dysfunction (TMD) were found. However, patients with prosthetic replacements had impaired periodontal health with accumulation of plaque and gingivitis. The conclusion of this study is that orthodontic space closure produces results that are well accepted by patients, does not impair temporomandibular joint (TMJ) function, and encourages periodontal health in comparison with prosthetic replacements. PMID- 11212607 TI - Tensile bond strength of a light-cured glass ionomer cement when used for bracket bonding under different conditions: an in vitro study. AB - The purpose of this study was to investigate the tensile bond strength of a new light-cured resin reinforced glass ionomer cement (Fuji Ortho LC), following the bonding of stainless steel brackets to 40 extracted human premolar teeth under four different enamel surface conditions: (1) non-etched, moistened with water; (2) etched, moistened with water; (3) etched, moistened with human saliva; and (4) etched, moistened with human plasma. The etched surface produced a higher bond strength than the non-etched surface when contaminated with distilled water. Contamination with human saliva resulted in a further increase in bond strength whilst plasma contamination produced an even higher strength. However, one-way analysis of variance showed no statistically significant difference between the various groups. After debonding, enamel and bracket base surfaces were examined for residual adhesive. The location of the adhesive also indicated improved bonding to etched enamel. This investigation shows that regardless of enamel surface pretreatment or environment, Fuji Ortho LC provides an adequate strength for bonding of orthodontic brackets. PMID- 11212608 TI - Public relations: it starts with you. PMID- 11212609 TI - The roots of EMS (getting back to your roots). PMID- 11212610 TI - Leveling the playing field for EMS services. AB - Pinellas County's emergency medical services system is a public utility model EMS system where as the purchaser of services, the EMS Authority can achieve the highest-quality, most cost-effective and most reliable EMS services. Pinellas County's use of an absolute level-playing-field, non-political bidding process that isolated quality and pricing issues has raised the bar for government purchasing. The entire EMS industry has seen how contract services can be evaluated fairly, in a non-political atmosphere, for the betterment of the citizens of the community. Our EMS Authority voted to award the contract to the best overall proposal based on fact and merit. The new agreement allows us to provide significantly improved paramedic ambulance services to our citizens at a substantial cost reduction to the county. PMID- 11212611 TI - How to conduct a DUI reenactment. PMID- 11212614 TI - [Morphological and karyotypic analysis of five blackfly species of the genus Cnetha (Diptera: Simulidae): description of the novel species from the Dzhrvezhskii canyon in Armenia]. AB - Morphological and karyotypical features of a new blackfly species Cnetha akopi sp. n. from Armenia are described. Comparative analysis of the new species and four closely related endemic species from Caucasus is performed. Photographic maps of polythene chromosomes are provided. PMID- 11212613 TI - [Seasonal dynamics of population of the feather mite Monojoubertia microphylla (Astigmata: Analgoidea: Proctophyllodidae) in the chaffinch Fringilla coelebs]. AB - The seasonal dynamics of the Monojoubertia microphylla micropopulations in different sex and age groups of the chaffinch Fringilla coelebs (Passeriformes: Fringillidae) have been studied during the nest and migration periods in the North-West of Russia. Three bird groups were determined within the chaffinch population during the study: adult males, adult females, immature chaffinches. Total number of bird specimens examined--353. In all chaffinch groups, the mean mite numbers and age structure of mite micropopulations were similar during the spring migration. The number of mites gradually increased from April to May. During the nest and autumn migration periods the seasonal dynamics of M. microphylla micropopulations were quite different on adult males and females of the chaffinch, because of different roles of male and female in the process of infestation the young bird generation. On the adult chaffinch males, the mite number continued to increase during the breeding period (June) and began to decrease significantly in July because of the postbreeding plumage moult. The mite number slowly decreased in the end of summer and the autumn migration. On the adult chaffinch females, the mite number decreased abruptly during the nest period. During this period, the chaffinch female sits together with nestlings for a long time, and the great number of its mites (about 60% of mite micropopulation) moves from the female onto the nestlings. The mite micropopulation migrated onto nestling is represented mainly by males, females (about 25% each) and tritonymphs (38%). Total mite number on the chaffinch females continued to decrease in July under the influence of postbreeding moult and slightly increased up to the autumn migration only. On the young chaffinches, the number of M. microphylla quickly increased during the second part of summer. It is the result of the great quota of mite instars being ready for the reproduction (imago, tritonymphs) within the micropopulation migrated from the chaffinch female onto the nestlings. The decrease of the M. microphylla micropopulation on the young birds was observed in the autumn only. In the end autumn migration (October), the mean numbers of mites on all chaffinch groups became approximately similar, but did not reach the mean rate observed in the beginning of the spring migration. During both migration periods, the imago and all preimaginal instars of M. microphylla were active, the diapause was not observed. In the beginning of spring migration and the end of autumn migration the main part of the mite micropopulations was represented by females, while in all other periods of chaffinch's stay in the North-West of Russia the immature instars predominated. PMID- 11212615 TI - [A catalog of mosquito species (Culicidae family) from the Asian region of Russia]. AB - A new checklist of mosquitoes (Culicidae) recorded in the Asian part of Russia includes 79 species. The checklist is provided with taxonomic comments and compared with ones compiled by previous authors. In a comparison to the checklist of Kukharchuk (1980) including 73 species, 10 species are added into the present checklist and 6 species mentioned by this author are excluded, as far they were not actually found in Asian part of Russia. The names of 9 species are chanced according to the International Code of Zoological Nomenclature (1966). In the checklist of Stojanovich and Scott (1995) including 64 species, 5 species were included erraneously and 21 species were missed. The classification and valid species names are listed according to the Catalog of the Mosquitoes of the World (Knight, Stone, 1977) and its supplements (Knight, 1978; Ward, 1984, 1992; Gaffigan, Ward, 1985), except 5 species. These species (Aedes implicatus, Ae. esoensis, Ae. rossicus, Ae. albescens, Ae. subdiversus) are considered in the comments to the checklist. PMID- 11212616 TI - [Genetic heterogeneity in natural populations of Microphallus piriformes and M. pygmaeus parthenites (Trematoda: Microphallidae)]. AB - The random amplified polymorphic DNA (RAPD) technique was applied for the studies of genetic heterogeny between several natural populations of trematodes belonging to the Microphallida family. Initially, the metacercariae from the daughter sporocysts infestating Littorina saxatilis and Littorina littorea periwinkles were used. Comparison of the banding patterns obtained for the different metacercariae within one sporocyst gave an unpredicted results. For two of three studied species (M. pygmaeus and M. pseudopygmaeus), the considerable differences in RAPD patterning was detected. According to the classical point of view, the process of cercariae (metacercariae in case of the "pygmaeus" group of microphallides) formation does not include DNA recombination. Because of that, all metacercariae within one single sporocyst should be genetically identical. However, data obtained clearly shows that at least in some cases it is not so. We can hardly believe that such result could be a methodological artifact, for not single difference in a RAPD patterns was recorded between the metacercariae within sporocysts of M. piriformes. Moreover, even the 100 fold dilution of the total DNA used for PCR amplification does not change the banding patterns. Hence, our results can not be explained by slight fluctuations in the DNA concentrations between the samples. The most evident conclusion is that we came across yet strange, but real phenomenon--some degree of genetic difference within the progeny of each of the sporocysts--metacercariae. However, the detailed study is needed to understand and interpret these observations correctly. Amplification of the total DNA extracted from the whole sporocysts (containing metacercariae) never showed any differences in RAPD patterns between the parasites been derived from one infestated snail (local parasite hemipopulation). That allowed us to compare different parasite populations referring the RAPD pattern of one sporocyst from a snail to as a representative of one local hemipopulation. Analysis of the RAPD-loci frequencies showed a considerable genetic differences between the subpopulations of M. piriformes, infestating different paraxenic intermediate hosts--L. saxatilis and L. obtusata. This phenomenon was statistically significant for 2 localities of 3 studied. No heterogeny within populations was recorded for M. pygmaeus. Both M. piriformes and M. pygmaeus are characterized by the genetic differentiation in the microgeographic scale (within the Chupa bay of the White sea, the longest distance between the analyzed localities is 20 km). According to the frequencies of the RAPD-loci, parasites from the sheltered locality differ significantly from the parasites of other two localities exposed to the open sea. For both species the degree of genetic similarity between the populations correlates positively with the distance between the localities. We can suppose that the population structure of microphallids depended mainly upon the population structures of their intermediate hosts, definitive hosts and geographical structure of the areal. However, taking into consideration the low motility of snails, we believe that the distribution, migration and species composition of the definitive hosts play the key role in the genetic structuring of M. pygmaeus and M. piriformes hemipopulations. As an addition, the RAPD analysis of the parasite populations from the Barents Sea (East cost of Murman peninsula) and North Sea (Western cost of Sweden) revealed no significant genetic differences between the worms from those places and from the White Sea. However in case of this macrogeographic comparison, insufficient number of samples does not allow us to draw any final conclusions. PMID- 11212618 TI - [Structure of the epithelium of the parasitic turbellaria Notenera ivanovi (Turbellaria: Fecampiida)]. AB - The ultrastructure of the epithelium in Notentera ivanovi (Turbellaria, Fecampiida) has been studied. Notentera ivanovi lacks the digestive system but has a pad of the epidermal cells on the dorsal side of the body, which seems to be similar to the digestive epidermis on LM. Both the ventral and dorsal epithelium are cellular, ciliated and not insunk (fig. 1, a). The ultrastructure of the ventral and dorsal epithelium is similar in essential features. The cells bear abundant microvilli, cilia and are very rich in mitochondria, but the cytoplasm does not contain lysosomes and shows no other indications of phago- or pinocytosis. The basal membrane of epithelial cells forms deep invaginations (fig. 1, [symbol: see text]), partly with dilations (fig. 1, a; 2, a) containing the lamellated material (3, [symbol: see text]). In the basal part of the cells the numerous Golgi apparatus and rare cysternae of the smooth endoplasmic reticulum were observed (fig. 2, a, [symbol: see text]). The epithelium consists of several types of cells, which differ in the structure of secretory granules. The most abundant type of cells contains the granules with the rough-fibrillated content (fig. 1, a; 2, [symbol: see text]; 3, a). The cells of this type cover most part of the body. In some cells the content of such granules becomes condensed and electron-dense granules appear (fig. 3, a, [symbol: see text]). Another type of cells contains the giant granules with the rough-fibrillated content (fig. 3, [symbol: see text]). Third type of the secret is the granules with the finely fibrillated content which is ejected by exocytosis. The cells of the second and third types form a separate areas of the epithelium of the dorsal side of the body but occasionally were observed in the ventral epithelium too. The epithelium of N. ivanovi differs from that in Kronborgia by the abundance and diversity of secretory contents. The role of the epithelium in the digestion remains conjectural. It seems to be mainly the suckering tissue transporting the low molecular nutrients. PMID- 11212617 TI - [Comparative morphofunctional analysis of the gastropod-trematode interactions]. AB - A morphofunctional aspect of pathogenesis in various mollusc--trematode combinations is very different. To evaluate the level of antagonism between the host and parasite, it is reasonable to use a summarized parameter of general physiological state of infected individuals. The somatic growth of the host could be used for that purpose. Analysis of original and reference data has shown, that the gastropod growth response to the trematode infection depends on the longevity of molluscs. The growth acceleration (gigantism) in infected individuals is common for snails with the intermediate longevity (3-4 yr), such as Hydrobia, Onobia and Bithynia (Prosobranchia: Rissoacea). As an exception, the gigantism is observed in the short-living species, which do not change the growth rate when they are parasitized: Biomphalaria, Bulinus, Helisoma and Lymnaea (Pulmonata: Basomathophora). Earlier, it was assumed that the single trend manifested in the infected long-living species (6-27 yr), such as Littorina (Prosobranchia: Littorinacea) and Cerithidea (Prosobranchia: Cerithiacea), in the decrease of the growth rate. The only case of the growth acceleration within the long-living molluscs was detected in the Littorina littorea from the White Sea infected with low pathogenic partenits of Cryptocotyle lingua (Heterophyidae). Based on the groups of snails with different longevity and being phylogenetically distant from each other, we can presume that the growth response to the infection correlates with the morphological peculiarities of hosts. The morphofunctional distinction in the system formed by trematodes and molluscs of different taxa are expressed in the parthenit localization in the host body and in the degree of digestive gland and/or gonad destriction. From the viewpoint of general physiological status of the host organism, the results of disfunctions in these organs are not similar. The destruction of digestive system ("energy power station" of organisms) is more fatal for infected individuals than a parasitic castration. Therefore, the localization of parasites in the mollusc gonad can be recognized as a parasitic adaptation to decrease the probability of a premature host's death and respectively to prevent the elimination of parasites. Phylogenetically distant gastropods with different life cycles use a diverse reproduction strategy, which implies a different proportion of gonad and digestive gland volume. Thus, snail species from different taxa are not similar in relation to the life space, which could be "granted" to the parasite without any risk to reduce a viability of the host. The space lack forces the parthenits parasitizing in the molluscs with the longer life span to occupy the digestive gland tissues, that increases their pathogenicity and decreases the host's growth rate. PMID- 11212619 TI - [Distribution of coccidians (Sporozoa: Coccidiida) in various systematic groups of fishes]. AB - There are about 250 coccidian species associated with fishes. They belong to 8 genera (Calyptospora, Cryptosporidium, Crystallospora, Eimeria, Epieimeria, Goussia, Isospora, Octosporella) and 3 families (Calyptosporidae, Cryptosporidiidae, Eimeriidae). Two genera are represented by great number of species associated with fishes: Eimeria--157 and Goussia--69 species. Most diverse fauna of coccidians was found in fishes of the class Actinopterigii; fishes of the class Elasmobranchii have significantly less number of coccidians. These parasites have never been recorded on the class Holocephali. Coccidian have been recorded in 55 orders of fishes. Within the Actinopterigii, the richest coccidian fauna is recorded from Cypriniformes and Perciformes. Accumulated data on host associations proves that coccidian species have mainly a restricted hosts specificity. PMID- 11212620 TI - [First record of the mite genus Neharpyrhyncuhus (Acari: Harpirhynchidae) in the Russian fauna]. AB - The mites of genus Neharpyrhynchus Fain, 1972 (Acari: Harpirhynchidae) are recorded from Rissia for first time. Two species, N. hippolae sp. n. from Hippolais icterina (Passeriformes: Sylviidae) and N. plumaris (Fritsch) from Fringilla coelebs (Passeroformes: Fringillidae) from N. W. Russia was found. N. hippolae sp. n., female holotype (all measurements in mkm, abbreviations--see Fain e.a., 1999): L 517, W 382, LS 179, WS 325, PA 27, thicker than PI 49 and PE 24, pts smooth, vi, ve [symbol: see text] sci are subequal, about 94, l5 247; propodosomal shield not divided; anterior region of pronotum with rounded verrucosites; venter without scales; legs I-II with 2 free segments and strongly developed lobes at their bases; legs III-IV with one segment, bears 4 and 5 setae respectively (in paratypes number of these setae is variable, 4-5). Male: L 227 254, W 210-219, LS 129-134, WS 170-183, pts are smooth, ve 78-87, sci 83-90, sce 89-95, h 90-110; penis 49-56 long; legs III with 2 free segments, basal segment bears seta, apical segment with 5-6 setae; legs IV with one free segment, it bears 4-5 setae. The new species is closely related to N. pilirostris (Berlese et Trouessart, 1889) and distinguished by characters as follows. N. hippolae sp. n. (female): the setae PI about 2 times are longer than PA and PE; the apical segment of legs III-IV bears 4-5 setae. N. pilirostris: setae PA, PI [symbol: see text] PE are subequal; the apical segment of legs III-IV bears 4 setae only. N. plumaris differs from closely related species N. novoplumaris Moss e.a., 1968 by characters as follows. In female of N. plumaris, the setae PA are subequal to PE and 1.6-1.8 times shorter than PI. In N. novoplumaris, the setae PA shorter than PI and PE. PMID- 11212622 TI - A global perspective on statutory Social Security programs for the sick. AB - Statutory sickness benefit programs have been adopted in 129 countries. Most have an employment-based strategy, social insurance, that restricts coverage to those in paid formal employment. The cash entitlements provided are predominantly earnings-related. Funding comes overwhelmingly from employer and employee contributions, with only a minority of countries providing government subsidies. A comparative-evaluative assessment methodology is used to assess national statutory intentions with respect to statutory social security provision for the sick. The best-designed statutory program is found in Sweden followed closely by France and then Australia, Austria and Germany. Algeria clearly leads the African rankings, as does Peru in Latin America, Iraq in the Middle East, and Nauru in the Pacific Islands. Turkmenistan has the best-designed statutory program in Asia, by a very small margin. In North America, Canada is well ahead of the United States. PMID- 11212621 TI - Difficulty or dependency? Effects of measurement scales on disability prevalence among older Americans. AB - This study examines how the prevalence of disability among subgroups of older persons is influenced by the activity of daily living (ADL) scale selected. Using the 1993 Survey of Asset and Income Dynamics of the Oldest Old, we construct four disability scales, ranging from difficulty performing an ADL to receiving help with an ADL, or dependency. In all instances, the difficulty scales produce substantially higher estimates of disability than the dependency scales. Larger percentages of women, Blacks, and less educated persons are classified disabled under all scales compared with men, Whites, and more educated persons. Specific subgroups are more sensitive to the scale used. The policy implications of using ADL scales to establish program eligibility are discussed. PMID- 11212623 TI - Quality, CQI, and reengineering in health services organizations. AB - Quality in health care is defined with a focus on satisfying customer needs. The contemporary management philosophies of continuous quality improvement (CQI) and reengineering are defined; attributes and applications of each are described. Criticism of reengineering appearing in the literature is presented. It is likely that CQI will remain a predominate management philosophy in health services, while reengineering may not endure in its form of radical change. PMID- 11212624 TI - Family health: an emerging paradigm for social workers. AB - The profession of social work has, since its inception, stressed the importance of the family system in social treatment. Even though the family has always been central to effective social work intervention, the framing of the family system from a family health perspective is new to the field. The goal of this paper is to present the empirical grounding of family health and the implications of this emerging paradigm for social policy. Family health is built on the biopsychosocial model and emphasizes the importance of the role of the family system in the social functioning of individuals. Family health is defined (Pardeck and Yuen, 1999, p. 1) "as a state of holistic well-being of the family system. Family health is manifested by the development of, and continuous interaction among, the physical, mental, emotional, social, economic, cultural and spiritual dimensions of the family which results in the holistic well-being of the family and its members." PMID- 11212625 TI - The Morton-Massaro law of information integration: implications for models of perception. AB - Information integration may be studied by analyzing the effect of 2 or more sources (e.g., auditory and visual) on participants' responses. Experiments show that ratios of response probabilities often factorize into components selectively influenced by only 1 source (e.g., 1 component affected by the acoustic source and another 1 affected by the visual source). This is called the Morton-Massaro law (MML). This article identifies conditions in which the law is optimal and notes that it reflects an implicit assumption about the statistics of the environment. Adherence to the MML can be used to assess whether the assumption is being made, and analyses of natural stimuli can be used to determine whether the assumption is reasonable. Feed-forward and interactive models subject to a channel separability constraint are consistent with the law. PMID- 11212626 TI - Perception and preference in short-term word priming. AB - Responding optimally with unknown sources of evidence (ROUSE) is a theory of short-term priming applied to associative, orthographic-phonemic, and repetition priming. In our studies, perceptual identification is measured with two alternative forced-choice testing. ROUSE assumes features activated by primes are confused with those activated by the target. A near-optimal decision discounts evidence arising from such shared features. Too little discounting explains the finding that primed words were preferred after passive viewing of primes. Too much discounting explains the findings of reverse preference after active processing of primes. These preference changes highlight the need to use paradigms (like the present ones) capable of separating preferential and perceptual components of priming. Evidence of enhanced perception was found only with associative priming and was very small in magnitude compared with preference effects. PMID- 11212627 TI - Signal-detection analysis of group decision making. AB - How effectively can groups of people make yes-or-no decisions? To answer this question, we used signal-detection theory to model the behavior of groups of human participants in a visual detection task. The detection model specifies how performance depends on the group's size, the competence of the members, the correlation among members' judgments, the constraints on member interaction, and the group's decision rule. The model also allows specification of performance efficiency, which is a measure of how closely a group's performance matches the statistically optimal group. The performance of our groups was consistent with the theoretical predictions, but efficiency decreased as group size increased. This result was attributable to a decrease in the effort that members gave to their individual tasks rather than to an inefficiency in combining the information in the members' judgments. PMID- 11212628 TI - DRC: a dual route cascaded model of visual word recognition and reading aloud. AB - This article describes the Dual Route Cascaded (DRC) model, a computational model of visual word recognition and reading aloud. The DRC is a computational realization of the dual-route theory of reading, and is the only computational model of reading that can perform the 2 tasks most commonly used to study reading: lexical decision and reading aloud. For both tasks, the authors show that a wide variety of variables that influence human latencies influence the DRC model's latencies in exactly the same way. The DRC model simulates a number of such effects that other computational models of reading do not, but there appear to be no effects that any other current computational model of reading can simulate but that the DRC model cannot. The authors conclude that the DRC model is the most successful of the existing computational models of reading. PMID- 11212629 TI - A Bayesian model for implicit effects in perceptual identification. AB - Retrieving effectively from memory (REM; R. M. Shiffrin & M. Steyvers, 1997), an episodic model of memory, is extended to implicit memory phenomena, namely the perceptual identification studies reported in R. Ratcliff and G. McKoon (1997). In those studies, the influence of prior study was greatest when words were presented most briefly and when forced-choice targets and foils were most similar. R. Ratcliff and G. McKoon use these data to argue against models in which prior study changes a word's representation. A model in which prior study changes a word's representation by adding context information is fit to their data; at test, the model uses a Bayesian decision process to compare the perceptual and context features associated with the test flash to stored traces. The effects of prior study are due to matching extra context information and are larger when alternatives share many features, thereby reducing noise that attenuates these effects. PMID- 11212630 TI - Is it time to pull the plug on the hostile versus instrumental aggression dichotomy? AB - Psychologists have often categorized human aggression as hostile or instrumental. Hostile aggression is "hot," impulsive behavior that is motivated by a desire to hurt someone; instrumental aggression is "cold," premeditated behavior used as a means to some other end. This dichotomy was useful to the early development of aggression theories and continues to capture important features of nonhuman aggression, but it has outlived its usefulness as a descriptor of fundamentally different kinds of human aggression. It is confounded with the automatic controlled information-processing dichotomy, and it fails to consider aggressive acts with multiple motives. Knowledge structure models of aggression easily handle these problems. Taking extreme measures to preserve the hostile instrumental dichotomy will delay further advances in understanding and controlling human aggression. Therefore, this seems a proper time to "pull the plug" and allow the hostile-instrumental aggression dichotomy a dignified death. PMID- 11212631 TI - Cognitive emissions of 1/f noise. AB - The residual fluctuations that naturally arise in experimental inquiry are analyzed in terms of their time histories. Although these fluctuations are generally relegated to a statistical purgatory known as unexplained variance, this article shows that they may harbor a long-term memory process known as 1/f noise. This type of noise has been encountered in a number of biological and physical systems and is theorized to be a signature of dynamic complexity. Its presence in psychological data appears to be associated with the most elementary aspect of cognitive process, the formation of representations. PMID- 11212632 TI - A modern learning theory perspective on the etiology of panic disorder. AB - Several theories of the development of panic disorder (PD) with or without agoraphobia have emerged in the last 2 decades. Early theories that proposed a role for classical conditioning were criticized on several grounds. However, each criticism can be met and rejected when one considers current perspectives on conditioning and associative learning. The authors propose that PD develops because exposure to panic attacks causes the conditioning of anxiety (and sometimes panic) to exteroceptive and interoceptive cues. This process is reflected in a variety of cognitive and behavioral phenomena but fundamentally involves emotional learning that is best accounted for by conditioning principles. Anxiety, an anticipatory emotional state that functions to prepare the individual for the next panic, is different from panic, an emotional state designed to deal with a traumatic event that is already in progress. However, the presence of conditioned anxiety potentiates the next panic, which begins the individual's spiral into PD. Several biological and psychological factors create vulnerabilities by influencing the individual's susceptibility to conditioning. The relationship between the present view and other views, particularly those that emphasize the role of catastrophic misinterpretation of somatic sensations, is discussed. PMID- 11212633 TI - Time scales in motor learning and development. AB - A theoretical framework based on the concepts and tools of nonlinear dynamical systems is advanced to account for both the persistent and transitory changes traditionally shown for the learning and development of motor skills. The multiple time scales of change in task outcome over time are interpreted as originating from the system's trajectory on an evolving attractor landscape. Different bifurcations between attractor organizations and transient phenomena can lead to exponential, power law, or S-shaped learning curves. This unified dynamical account of the functions and time scales in motor learning and development offers several new hypotheses for future research on the nature of change in learning theory. PMID- 11212634 TI - Do infant rats cry? AB - In the current revival of interest in the emotional and mental lives of animals, many investigators have focused attention on mammalian infants that emit distress vocalizations when separated from the home environment. Perhaps the most intensively studied distress vocalization is the ultrasonic vocalization of infant rats. Since its discovery, this vocalization has been interpreted both as a communicatory signal for the elicitation of maternal retrieval and as the manifestation of emotional distress. In contrast, the authors examined the cardiovascular causes and consequences of the vocalization, and on the basis of this work, they hypothesized that the vocalization is the acoustic by-product of the abdominal compression reaction (ACR), a maneuver that results in increased venous return to the heart. Therefore, the vocalization may be analogous to a sneeze, serving a physiological function while incidentally producing sound. PMID- 11212635 TI - Hyperbolic value addition and general models of animal choice. AB - Three mathematical models of choice--the contextual-choice model (R. Grace, 1994), delay-reduction theory (N. Squires & E. Fantino, 1971), and a new model called the hyperbolic value-added model--were compared in their ability to predict the results from a wide variety of experiments with animal subjects. When supplied with 2 or 3 free parameters, all 3 models made fairly accurate predictions for a large set of experiments that used concurrent-chain procedures. One advantage of the hyperbolic value-added model is that it is derived from a simpler model that makes accurate predictions for many experiments using discrete trial adjusting-delay procedures. Some results favor the hyperbolic value-added model and delay-reduction theory over the contextual-choice model, but more data are needed from choice situations for which the models make distinctly different predictions. PMID- 11212636 TI - Making more by working less. PMID- 11212637 TI - Your career guide. Solving the midcareer puzzle. Make your practice more profitable. PMID- 11212638 TI - My other career: how the military enriches my practice. PMID- 11212639 TI - Your career guide. Solving the midcareer puzzle. Do you have the right stuff to go solo? PMID- 11212640 TI - "We've proved that David can compete with Goliath". PMID- 11212641 TI - Your career guide. Solving the midcareer puzzle. Knowing when it's time to move on. PMID- 11212642 TI - Your career guide. Surveying the landscape. Where the jobs are. PMID- 11212643 TI - Your career guide. Surveying the landscape. What they're paying. PMID- 11212644 TI - Your career guide. Surveying the landscape. Are you cut out to be a country doc? PMID- 11212645 TI - The big step: starting a small-town practice. PMID- 11212646 TI - Your career guide. Surveying the landscape. Knowing who you are and what you want. PMID- 11212647 TI - At your service. PMID- 11212648 TI - Your career guide. Landing the job you want. Job search strategies that really work. PMID- 11212649 TI - The frantic job search of an IMG. PMID- 11212650 TI - Your career guide. Landing the job you want. Shape a contract you'll be glad you signed. PMID- 11212651 TI - Your career guide. Solving the midcareer puzzle. Can you find happiness where you are? PMID- 11212652 TI - My cure for burnout: job sharing. PMID- 11212653 TI - [BLNK deficiency]. PMID- 11212654 TI - [Surrogate light chain deficiency]. PMID- 11212655 TI - [Primary combined immunodeficiency due to a defect in interleukin 2 production]. PMID- 11212656 TI - [Primary CD4 deficiency]. PMID- 11212657 TI - [Primary CD7 deficiency]. PMID- 11212658 TI - [Primary immunodeficiency associated with defective signal transduction in T cells]. PMID- 11212659 TI - [Primary combined immunodeficiency due to defective transcription of multiple T cell cytokine genes]. PMID- 11212660 TI - [CD8 deficiency]. PMID- 11212661 TI - [Idiopathic CD4+ T lymphocytopenia]. PMID- 11212662 TI - [DiGeorge anomaly (DiGeorge syndrome)]. PMID- 11212663 TI - [Wiskott-Aldrich syndrome]. PMID- 11212664 TI - [Ataxia-telangiectasia(AT), Louis-Bar syndrome]. PMID- 11212665 TI - [Chediak-Higashi syndrome]. PMID- 11212666 TI - [Kostmann syndrome, hereditary neutropenia]. PMID- 11212667 TI - [Pelger-Huet anomaly]. PMID- 11212668 TI - [Shwachman syndrome]. PMID- 11212669 TI - [Deficiency of leukocyte glutathione reductase, deficiency of leukocyte glutathione peroxidase]. PMID- 11212670 TI - [Neutrophil cytoskeletal disease]. PMID- 11212672 TI - [Neutrophil glucose-6-phosphate dehydrogenase deficiency]. PMID- 11212671 TI - [MHC class I deficiency]. PMID- 11212673 TI - [Tuftsin deficiency]. PMID- 11212674 TI - [Chronic benign neutropenia(CBN)]. PMID- 11212675 TI - [Chronic idiopathic neutropenia]. PMID- 11212676 TI - [Cyclic neutropenia]. PMID- 11212677 TI - [Lazy-leukocyte syndrome]. PMID- 11212678 TI - [Neutrophil secondary granule deficiency]. PMID- 11212679 TI - [Leukocyte adhesion deficiency, type I]. PMID- 11212680 TI - [Leukocyte adhesion deficiency, type II]. PMID- 11212681 TI - [Neutrophil pyruvate kinase deficiency]. PMID- 11212683 TI - [MHC class II deficiency (CIITA/RFX deficiency)]. PMID- 11212682 TI - [Chronic granulomatous disease]. PMID- 11212684 TI - [Myeloperoxidase deficiency]. PMID- 11212685 TI - [C1q deficiency]. PMID- 11212686 TI - [C1r/C1s deficiency]. PMID- 11212687 TI - [C2 deficiency]. PMID- 11212688 TI - [C3 deficiency]. PMID- 11212689 TI - [C4 deficiency]. PMID- 11212690 TI - [C5 deficiency/dysfunction]. PMID- 11212691 TI - [C6 deficiency]. PMID- 11212692 TI - [C7 deficiency]. PMID- 11212693 TI - [Nezelof's syndrome]. PMID- 11212694 TI - [C8 alpha-gamma chain/beta chain deficiency]. PMID- 11212695 TI - [C9 deficiency]. PMID- 11212696 TI - [C1 inhibitor deficiency]. PMID- 11212697 TI - [Factor H deficiency]. PMID- 11212698 TI - [Factor D deficiency]. PMID- 11212699 TI - [Properdin deficiency]. PMID- 11212700 TI - [C4 binding protein deficiency]. PMID- 11212701 TI - [HRF20(CD59, MACIF) deficiency]. PMID- 11212702 TI - [Omenn syndrome]. PMID- 11212703 TI - [CR1 deficiency]. PMID- 11212704 TI - [CR3/4 deficiency]. PMID- 11212705 TI - [Paroxysmal nocturnal hemoglobinuria]. PMID- 11212706 TI - [CD46 deficiency]. PMID- 11212707 TI - [C5a inhibitor deficiency]. PMID- 11212708 TI - [Mannose-binding lectin(MBL) deficiency]. PMID- 11212709 TI - [Factor I deficiency]. PMID- 11212710 TI - [Diseases associated with C1q abnormalities]. PMID- 11212711 TI - [Bloom syndrome]. PMID- 11212712 TI - [Fanconi anemia]. PMID- 11212713 TI - [ICF syndrome]. PMID- 11212714 TI - [T cell activation defects]. PMID- 11212715 TI - [Nijmegen breakage syndrome]. PMID- 11212716 TI - [Seckel syndrome]. PMID- 11212717 TI - [Down's syndrome]. PMID- 11212718 TI - [Turner syndrome]. PMID- 11212719 TI - [Xeroderma pigmentosum]. PMID- 11212720 TI - [Abnormal condensation of the heterochromatin of chromosomes 1, 9 and 16]. PMID- 11212721 TI - [Deletions and rings of chromosome 18]. PMID- 11212722 TI - [Dubowitz syndrome]. PMID- 11212723 TI - [Familial intestinal polyatresia(FIPA)]. PMID- 11212724 TI - [Immunodeficiency and partial albinism, Griscelli syndrome]. PMID- 11212725 TI - [Asplenia syndrome(Ivemark syndrome)]. PMID- 11212726 TI - [Netherton syndrome]. PMID- 11212727 TI - [Papillon-Lefevre syndrome]. PMID- 11212728 TI - [Schimke immuno-osseous dysplasia]. PMID- 11212729 TI - [Hutchinson-Gilford progeria syndrome]. PMID- 11212730 TI - [Adenosine deaminase deficiency]. PMID- 11212731 TI - [Dyskeratosis congenita]. PMID- 11212732 TI - [Short-limb skeletal dysplasia with immunodeficiency]. PMID- 11212733 TI - [Acrodermatitis enteropathica]. PMID- 11212734 TI - [Short-limbed dwarfism with immunodeficiency, cartilage-hair hypoplasia, metaphyseal chondrodysplasia, Gutti-Lux syndrome]. PMID- 11212735 TI - [Dysgenesis of the corpus callosum]. PMID- 11212736 TI - [Growth retardation, facial anomalies and immunodeficiency]. PMID- 11212737 TI - [Anhidrotic ectodermal dysplasia]. PMID- 11212738 TI - [Mannosidosis]. PMID- 11212740 TI - [Hereditary transcobalamin II deficiency]. PMID- 11212739 TI - [Hereditary orotic aciduria]. PMID- 11212741 TI - [Glycogen storage disease type Ib]. PMID- 11212742 TI - [Reticular dysgenesis]. PMID- 11212743 TI - [Biotin-responsive multiple carboxylase deficiency]. PMID- 11212744 TI - [Methylmalonic acidemia]. PMID- 11212745 TI - [Hyper IgE syndrome]. PMID- 11212746 TI - [Familial hypercatabolic hypoproteinemia]. PMID- 11212747 TI - [Myotonic dystrophy]. PMID- 11212748 TI - [Intestinal lymphangiectasia]. PMID- 11212749 TI - [Chronic mucocutaneous candidiasis (CMCC)]. PMID- 11212750 TI - [HIV infection and AIDS]. PMID- 11212751 TI - [Severe combined immunodeficiency]. PMID- 11212752 TI - [Extrahepatic manifestations of viral hepatitis]. PMID- 11212753 TI - [Immunologic disorders associated with herpesvirus infection]. PMID- 11212754 TI - [Immunologic disorders associated with virus infections]. PMID- 11212755 TI - [Brill-Zinsser disease]. PMID- 11212756 TI - [Spirochetal infection]. PMID- 11212757 TI - [Protozoan diseases]. PMID- 11212758 TI - [Helminth infection and immunodepression]. PMID- 11212759 TI - [Malignant lymphoma]. PMID- 11212760 TI - [Acute myelogenous leukemia]. PMID- 11212761 TI - [Multiple myeloma]. PMID- 11212762 TI - [Chronic myelogenous leukemia]. PMID- 11212763 TI - [Acute lymphoblastic leukemia and chronic lymphocytic leukemia]. PMID- 11212764 TI - [Myelofibrosis]. PMID- 11212765 TI - [Immunodeficiency in autoimmune diseases]. PMID- 11212766 TI - [Purine nucleoside phosphorylase deficiency]. PMID- 11212767 TI - [Immunodeficiency induced by antineoplastic agents]. PMID- 11212768 TI - [Drug induced immunodeficiency]. PMID- 11212769 TI - [Immunodeficiency induced by immunosuppressive agents]. PMID- 11212770 TI - [D-penicillamine-induced immune deficiency]. PMID- 11212771 TI - [Cushing's syndrome]. PMID- 11212772 TI - [Febrile neutropenia]. PMID- 11212774 TI - [Altered immunity in patients with alcoholism]. PMID- 11212773 TI - [Werner syndrome]. PMID- 11212775 TI - [Common variable immunodeficiency(CVID)]. PMID- 11212776 TI - [Malnutrition, essential trace element deficiency, vitamin deficiency]. PMID- 11212777 TI - [Post-thymectomy syndrome]. PMID- 11212778 TI - [Post-splenectomy syndrome]. PMID- 11212779 TI - [Stress]. PMID- 11212780 TI - [Autoimmune disorders in diabetes mellitus]. PMID- 11212781 TI - [Nephrotic syndrome]. PMID- 11212782 TI - [Immunological response to severe burn]. PMID- 11212783 TI - [Good syndrome, immunodeficiency with thymoma]. PMID- 11212784 TI - [Radiation injury]. PMID- 11212785 TI - [Chronic renal failure, uremia]. PMID- 11212786 TI - [Acquired disorders of the complement system]. PMID- 11212787 TI - [Antibody-mediated thrombosis]. PMID- 11212788 TI - [Castleman's disease]. PMID- 11212789 TI - [Ankylosing spondylitis]. PMID- 11212790 TI - [Reactive arthritis(Reiter's syndrome)]. PMID- 11212791 TI - [Psoriatic arthritis]. PMID- 11212792 TI - [Arthropathies of inflammatory bowel diseases]. PMID- 11212793 TI - [HTLV-I associated arthropathy (HAAP)--a review]. PMID- 11212794 TI - [X-linked lymphoproliferative syndrome (XLP)]. PMID- 11212795 TI - [Hermans syndrome]. PMID- 11212796 TI - [Chronic fatigue syndrome]. PMID- 11212797 TI - [Secondary neutrophil dysfunction]. PMID- 11212798 TI - [Compromised host syndrome]. PMID- 11212799 TI - [Histiocytic necrotizing lymphadenitis]. PMID- 11212800 TI - [Inflammatory abdominal aortic aneurysm]. PMID- 11212802 TI - [Kimura's disease(eosinophilic lymphfolliculoid granuloma]. PMID- 11212801 TI - [Granular lymphocyte-proliferative disorders, lymphoproliferative disease of granular lymphocytes]. PMID- 11212803 TI - [Familial hemophagocytic lymphohistiocytosis(FHL)]. PMID- 11212804 TI - [Malignant tumor-associated hemophagocytic syndrome(MAHS)]. PMID- 11212805 TI - [Hyper IgM syndrome]. PMID- 11212806 TI - [Virus-associated hemophagocytic syndrome(VAHS)]. PMID- 11212807 TI - [Bacteria-associated hemophagocytic syndrome(BAHS)]. PMID- 11212808 TI - [Autoimmune-associated hemophagocytic syndrome(AAHS)]. PMID- 11212809 TI - [Postmyocardial infarction syndrome]. PMID- 11212810 TI - [Postcardiotomy syndrome]. PMID- 11212811 TI - [Idiopathic myocarditis and pericarditis]. PMID- 11212812 TI - [Kawasaki vasculitis]. PMID- 11212813 TI - [X-linked agammaglobulinemia]. PMID- 11212814 TI - [Langerhans cell histiocytosis(LCH)]. PMID- 11212815 TI - [Crow-Fukase (POEMS) syndrome]. PMID- 11212816 TI - [Monoclonal gammopathy of undetermined significance(MGUS)]. PMID- 11212817 TI - [Disseminated eosinophilic collagen disease]. PMID- 11212818 TI - [Mastocytosis]. PMID- 11212819 TI - [Orbital myositis]. PMID- 11212820 TI - [Immunoblastic lymphadenopathy]. PMID- 11212821 TI - [Alloimmune disease]. PMID- 11212822 TI - [Tuberculosis and Legionella infection on immunocompromised host]. PMID- 11212823 TI - [Fungal infection in immunocompromised hosts]. PMID- 11212824 TI - [Autosomal recessive agammaglobulinemia]. PMID- 11212826 TI - [X-linked hypogammaglobulinemia with growth hormone deficiency]. PMID- 11212825 TI - [Antibody deficiency with normal(or elevated) immunoglobulins]. PMID- 11212827 TI - [Transient hypogammaglobulinemia of infancy]. PMID- 11212828 TI - [Ig heavy-chain gene deletions]. PMID- 11212829 TI - [Selective deficiency of IgA subclass]. PMID- 11212830 TI - [Deficiency of secretory IgA]. PMID- 11212831 TI - [Selective IgA deficiency]. PMID- 11212832 TI - [Selective IgG deficiency]. PMID- 11212833 TI - [IgG subclass deficiency]. PMID- 11212834 TI - [CD3 subunit deficiencies]. PMID- 11212836 TI - [Isolated IgE deficiency]. PMID- 11212835 TI - [Selective IgM deficiency]. PMID- 11212837 TI - [IgA-IgM deficiency]. PMID- 11212838 TI - [Light-chain deficiency(kappa-chain deficiency, lambda-chain deficiency]. PMID- 11212839 TI - Characterization of glyoxalase I (E. coli)-inhibitor interactions by electrospray time-of-flight mass spectrometry and enzyme kinetic analysis. AB - Potential inhibitors of the enzyme glyoxalase I from Escherichia coli have been evaluated using a combination of electrospray mass spectrometry and conventional kinetic analysis. An 11-membered library of potential inhibitors included a glutathione analogue resembling the transition-state intermediate in the glyoxalase I catalysis, several alkyl-glutathione, and one flavonoid. The E. coli glyoxalase I quaternary structure was found to be predominantly dimeric, as is the homologous human glyoxalase I. Binding studies by electrospray revealed that inhibitors bind exclusively to the dimeric form of glyoxalase I. Two specific binding sites were observed per dimer. The transition-state analogue was found to have the highest binding affinity, followed by a newly identified inhibitor; S-(2 [3-(hexyloxy)benzoyl]-vinyl)glutathione. Kinetic analysis confirmed that the order of affinity established by mass spectrometry could be correlated to inhibitory effects on the enzymatic reaction. This study shows that selective inhibitors may exist for the E. coli homologue of the glyoxalase I enzyme. PMID- 11212840 TI - Microscopic analysis of polymerization and fragmentation of individual actin filaments. PMID- 11212842 TI - Murine retroviral vector producer cells survival and toxicity in the dog liver. AB - To develop a safe method to target gene delivery into intrahepatic tumors, we examined the toxicity of intrahepatic (IH) injection of retroviral vector producer cells (VPC) into the canine liver. VPC have been demonstrated to effectively transfer genes in vivo. To evaluate for adverse effects form xenogeneic cell transplantation, mongrel dogs were injected IH with 1 x 10(9) murine LTKOSN.2 VPC divided into three aliquots. The animals were then monitored for acute toxicity induced by the VPC. The intraoperative IH injections of the cells were tolerated without difficulty. Starting 7 days after IH injection, the dogs then received intravenous ganciclovir (GCV) twice daily (5 mg/kg) for 7 days. GCV treatment did not cause significant toxicities. Dogs underwent serial blood tests to evaluate bone marrow, renal, liver and immunological function. Complete blood counts, electrolytes, liver function and renal function tests remained normal except for mild elevations of alkaline phosphatase. Histologic examination of liver tissues from the IH injection site revealed no apparent normal tissue destruction induced by the VPC. Two of the four treated dogs underwent liver biopsy on day 3. These biopsy specimens were cultured and persistent, viable VPC were recovered. The dogs mounted an antibody response to the murine VPC that was first demonstrated 5 days post injection. PCR analysis demonstrated low level gene transfer into dog liver tissue. Overall, our results demonstrate that IH xenogeneic VPC injections are not accompanied by significant adverse effects over a 1 month period following administration into the canine liver. These data support the safety aspects of using murine VPC in Phase I clinical trials. PMID- 11212841 TI - Murine retroviral vector producer cells survival and toxicity in the peritoneal cavity of dogs. AB - Retroviral vector producer cells (VPC) can effectively transfer genes in vivo. To develop a safe method to target gene delivery into intraperitoneal tumors, we have examined the toxicity of intraperitoneal (i.p.) infusion of retroviral VPC in a xenogeneic canine model. Mongrel dogs were injected intraperitoneally (i.p.) with 2 x 10(9) murine LTKOSN.2 VPC. The animals did not demonstrate acute toxicity and tolerated the i.p. infusion of the cells without difficulty. Starting 7 days after i.p. injection, the dogs received intravenous injections of ganciclovir (GCV) twice daily (5 mg/kg) for 7 days. The treatment dogs underwent peritoneal washings on days 3, 7 and 14 after their initial infusion of cells to study the persistence of the VPC. GCV treatment did not cause significant toxicities. Dogs underwent serial blood tests to evaluate bone marrow, renal, liver and immunological function. Complete blood counts, electrolytes and renal function remained normal throughout the study. Although, transient mild elevations occurred of serum alkaline phosphate, the remaining hepatic enzymes remained normal. Histologic examination of tissues from animals sacrificed after the i.p. administration of the VPC revealed no tissue destruction of the normal peritoneal lining. The dogs mounted an antibody response to the murine VPC that was first observed 7 days post injection. PCR analysis of selected tissues after GCV administration did not reveal persistent vector sequences. These results demonstrated that the injection of xenogeneic VPC is not accompanied by significant adverse effects over a 1 month period following administration into the canine peritoneal cavity. These data support the potential clinical application of the VPC in Phase I clinical trials in humans. PMID- 11212843 TI - Prognostic significance of matrix metalloproteinase expression in colorectal carcinomas. AB - The matrix metalloproteinases (MMPs) are a family of enzymes that degrade the extracellular matrix (ECM) and are considered to be important in neoplastic cell invasion and metastasis. Structural changes in the extracellular matrix are necessary for cell migration during tissue remodeling and neoplastic cell invasion. Histochemical expression of MMP-2, -3, -9, -10, and -13 was observed in 19 human colorectal carcinomas (CCs) employing an indirect alkaline phosphatase (AP) conjugated antigen detection technique. Evaluation of the results was based on (a) the percent of neoplastically transformed cells that reacted positively and (b) a measure of staining intensity [graded from A (highest) to D]. The two forms of stromelysin (SL), types 1 (MMP-3) and 2 (MMP-10), share 82% sequence homology, but exhibit differences in cellular synthesis and inducibility by cytokines and growth factors in vitro. Strong overall expression of MMP-3 and -10 was found in all CC cases observed, especially in the ECM adjacent to blood vessels. Positive immunoreactivity could be seen for these two MMPs in the ECM surrounding over 90% of the neoplastically transformed cells, and the staining intensity was also the strongest possible (A,B). Weak (surrounding anywhere between 10% and 90% of the neoplastically transformed cells, and of strong A,B intensity) expression of MMP-2 (gelatinase A) and MMP-9 (gelatinase B), two cytokine-induced MMPs, was also observed in CCs. Expression of collagenase-3 (MMP 13), an endopeptidase characterized by a potent degrading activity against a wide spectrum of substrates, was not defined in the CCs cases observed by us. It is clear that the activation of MMPs and their inhibitors occurs in a very well orchestrated manner. The necessity of these same enzymes for the extravasation and infiltration of lymphocytes into regions of chronic local inflammation, as associated with neoplastically transformed masses of cells, may aid the transformed cells which have already acquired a metastatic immunophenotype to enter the peripheral circulation. Further characterization of the expression and utilization of MMPs and their inhibitors in the progression of solid human neoplasms should lead to the development of novel anti-cancer therapies. PMID- 11212844 TI - Matrix metalloproteinase expression in childhood medulloblastomas/primitive neuroectodermal tumors. AB - The matrix metalloproteinases (MMPs) are a family of enzymes that degrade the extracellular matrix (ECM) and are considered to be important in neoplastic cell invasion and metastasis. Structural changes in the extracellular matrix are necessary for cell migration during tissue remodeling and neoplastic invasion. Expression of MMP-2, -3, -9, -10, and -13 was investigated in human childhood medulloblastomas (MEDs)/primitive neuroectodermal tumors (PNETs) employing an indirect alkaline phosphatase conjugated immunohistochemical antigen detection technique. Evaluation of the results was based on (a) the percent of neoplastically transformed tissue that reacted positively and (b) a measure of immunoreactivity or staining intensity [graded from A (highest) to D (negative)]. Strong overall expression of MMP-3 and -10 was found in MEDs/PNETs, especially in the ECM adjacent to blood vessels. Positive immunoreactivity was identified for these two MMPs in the ECM surrounding over 90% of the neoplastically transformed cells with the staining intensity being also the strongest possible (A,B). These two forms of stromelysin (SL), types 1 (MMP-3) and 2 (MMP-10), share 82% sequence homology, but exhibit differences in cellular synthesis and inducibility by cytokines and growth factors in vitro. Focal (surrounding less than 10% of the neoplastically transformed cells) but strong (A,B) immunoreactivity was determined for collagenase-3 (MMP-13), an endopeptidase characterized by a potent degrading activity against a wide spectrum of substrates. Weak (surrounding anywhere between 10% and 90% of the neoplastically transformed cells, and of B and B,C intensity) expression of MMP-2 (gelatinase A) and MMP-9 (gelatinase B), two cytokine-induced MMPs, was also observed. It is clear that the activation of MMPs and their inhibitors occurs in a very well orchestrated manner. The necessity of these same enzymes for the extravasation and infiltration of lymphocytes into regions of chronic local inflammation, as associated with neoplastically transformed masses of cells, may aid the transformed cells which have already acquired a more aggressive, metastatic immunophenotype (IP) to enter the peripheral circulation. Further characterization of the expression and utilization of MMPs and their inhibitors in the progression of solid human malignancies should lead to the development of novel anti-cancer therapies. PMID- 11212846 TI - 1st International Workshop on Coronary MR and CT Angiography. Lyon, France, 1-3 October 2000. Abstracts. PMID- 11212845 TI - Significant differences in the matrix metalloproteinase expression profiles of spontaneous medulloblastomas/primitive neuroectodermal tumors as compared with their xenografted, established tumor cell line derived counterparts. AB - Matrix metalloproteinases (MMP) are a family of zinc-dependent enzymes which degrade various components of the extracellular matrix (ECM) and play an important role in facilitating neoplastic cell invasion and metastasis. Structural changes in the extracellular matrix are necessary for cell migration during tissue remodeling and tumor invasion. Expression of MMP-2, -3, -9, -10, and -13 was investigated in both spontaneous and xenografted (cells derived from an established cell-line [DAOY#3]) childhood medulloblastomas (MEDs)/primitive neuroectodermal tumors (PNETs) employing an indirect alkaline phosphatase conjugated immunocytochemical technique. Evaluation of the results was based on (a) the percent of neoplastically transformed tissue that reacted positively and (b) a measure of staining intensity [graded from A (highest) to D]. The two forms of stromelysin (SL), types 1 (MMP-3) and 2 (MMP-10), share 82% sequence homology, but exhibit differences in cellular synthesis and inducibility by cytokines and growth factors in vitro. Strong overall expression of MMP-3 and -10 was found only in the spontaneous MEDs/PNETs, especially in the ECM adjacent to blood vessels. Positive immunoreactivity could be seen for these two MMPs in the ECM surrounding over 90% of the neoplastically transformed cells in the spontaneous cases, and the staining intensity was also the strongest possible (A,B). Focal (surrounding less than 10% of the neoplastically transformed cells) but strong (A,B) immunoreactivity for collagenase-3 (MMP-13) was also only detected in spontaneous MEDs/PNETs, an endopeptidase characterized by a potent degrading activity against a wide spectrum of substrates. Weak (surrounding anywhere between 10% and 90% of the neoplastically transformed cells, and of B and B,C intensity) expression of MMP-2 (gelatinase A) and MMP-9 (gelatinase B), two cytokine-induced MMPs, was also observed in the spontaneous cases. Staining for MMP-2 was negative in the xenografted MEDs/PNETs. The only positive immunoreactivity in the xenografted MEDs/PNETs was observed in the case of MMP-9, with expression of strong intensity in the ECM surrounding over 90% of the neoplastically transformed xenografted MED/PNET cells (++++; A,B). It is clear that the activation of MMPs and their inhibitors occurs in a very well orchestrated manner. The data presented here suggest that there are significant differences in the pathophysiology of spontaneous and xenografted human neoplasms, which further establishes the already detected limitations of such models in preclinical cancer research. PMID- 11212847 TI - Review of publications. PMID- 11212848 TI - [Reverse transcriptase polymerase chain reaction and immunocytochemistry of bone marrow aspiration specimen and peripheral blood for detection of microdisseminated prostatic carcinoma. A comparative analysis]. AB - Reverse transcriptase-polymerase chain reaction (RT-PCR) assay for prostate specific antigen and immunocytochemistry for cytokeratin-18 (CK-18) are tests for the detection of microdisseminated carcinoma of the prostate. Bone marrow aspirates and peripheral venous blood from 50 patients with clinically organ confined prostate cancer were examined. The rate of positive results was independent of the pT stage, serum PSA, and previous antiandrogen treatment. RT PCR and immunocytochemistry have to be tested under standardized conditions in prospective trials, and the results have to be compared to the serum PSA follow up. PMID- 11212849 TI - [Surgical procedures for patients with hyperparathyroidism]. PMID- 11212850 TI - [Survey on attitudes of sentinel clinicians in Yokohama about infectious diseases surveillance system]. PMID- 11212852 TI - [Symptomatic cluster headache. Expression of multiple sclerosis relapse with magnetic resonance tomography detection of pontomedullary lesion in the ipsilateral trigeminal nucleus area]. AB - We describe a 25-year-old male who developed, in the course of an acute exacerbation of his multiple sclerosis, cluster headache-like attacks which responded to oxygen therapy. Magnetic resonance imaging revealed a lesion in the area of the ipsilateral pontomedullary trigeminal nuclei. This symptomatic case and other published cases are most probably explained by an activation of the trigeminovascular system as it is assumed for primary headache syndromes. PMID- 11212851 TI - Correlates of self-efficacy in diabetes self-care among Hispanic adults with diabetes. AB - PURPOSE: The purpose of this study was to examine factors associated with increased diabetes self-efficacy among insulin-requiring Hispanic adults with diabetes. METHODS: A cross-sectional survey design was used to obtain self reported data on a nonrandom sample of 97 insulin-requiring Hispanic adults with diabetes. The Insulin Management Diabetes Self-Efficacy Scale (IMDSES) was translated into Spanish and administered with a demographic questionnaire by trained bilingual/bicultural interviewers in each respondent's own home. Factor analysis of the IMDSES revealed 4 subscales that corresponded with major diabetes self-care management behaviors. RESULTS: Respondents gave low to average self efficacy ratings on their ability to manage all aspects of their disease. Behaviors that required problem solving in changing circumstances received the lowest scores. Attending diabetes classes and having home nursing visits were associated with an increased sense of self-efficacy, particularly as it related to diet and insulin. English-speaking ability was associated with a general sense of self-efficacy in managing diabetes care. CONCLUSIONS: The model tested was able to explain modest levels of self-efficacy, particularly in 2 of the most important diabetes management areas, insulin and diet management. PMID- 11212853 TI - Congress close to finalizing Medicare relief package for SNFs, other providers. PMID- 11212854 TI - New perspectives in the treatment of breast cancer. Introduction. PMID- 11212855 TI - What's all this talk about randomized, double blind, clinical trials? PMID- 11212856 TI - Prophylaxis against fungal infections and cytomegalovirus disease after bone marrow transplantation. AB - Among the serious complications associated with bone marrow transplantation are invasive fungal infections caused by organisms such as Candida and Aspergillus species and end-organ disease caused by cytomegalovirus (CMV). Successful prevention of these complications can have a significant impact on morbidity and mortality. The primary option for prophylaxis against fungal infections is fluconazole (Diflucan). Low doses of intravenous amphotericin B may be useful where there is a higher rate of aspergillosis. Itraconazole (Sporanox) and nasal amphotericin B are other options that have been less well studied. The development of fluconazole-resistant candidiasis may become problematic. Ganciclovir (Cytovene) is useful for the prevention of end-organ disease caused by CMV but carries a significant risk for neutropenia. New techniques for the early detection of CMV infection should allow prophylaxis to be targeted to patients at highest risk of developing CMV disease. It is critical to clearly define the risk factors for fungal and CMV disease in the individual patient in order to minimize adverse effects and provide the optimal prophylactic benefit. PMID- 11212857 TI - Spontaneous neoplastic regression: the significance of apoptosis. AB - In mammalian cells, neoplastic transformation has a direct relationship with the expression of oncogenes, the production of certain growth factors and with the mutation, loss or simple inactivation of the function of tumor suppressor genes. Genes for suppression of the development of the malignant immunophenotype, as well as inhibitory growth factors have regulatory functions within the normal processes of cell division and differentiation. Telomerase (a ribonucleoprotein polymerase) activation is frequently observed in various types of neoplastic cell transformation. Telomerase activation is regarded as essential for cell immortalization and its inhibition may result in spontaneous regression (SR) of neoplasms. SR of neoplasms occurs when the malignant tumor mass partially or completely disappears without any treatment or as a result of a therapy considered inadequate to influence systemic neoplastic disease. This definition makes it clear that the term SR applies to neoplasms in which the malignant disease is not necessarily cured, and to cases where the regression may not be complete or permanent. A number of possible mechanisms of SR are reviewed, with the understanding that no single mechanism can completely account for this phenomenon. The application of the newest immunological, molecular biological and genetic insights for more individualized anticancer immunotherapy (biotherapy) is also discussed. In conclusion, of all the possible mechanisms of SR of neoplasms, programmed cell death (PCD) or apoptosis is involved in each. The immunological mechanism is probably the main effector mechanism of SR in human neoplasms with its trigger being apoptosis. The treatments of the tumor, such as with various anti-neoplastic drugs or radiation or immunotherapy, all include the basic mechanism of programmed cell death or apoptosis. Without apoptosis, there is practically no tumor regression, none of any kind. PMID- 11212858 TI - Systolic heart failure: practical implementation of standard guidelines. AB - Congestive heart failure (CHF) is being described as an epidemic of the next decade. Despite significant advances in the treatment of systolic heart failure, community mortality remains high, which is partly due to a failure to implement standard guidelines. The purpose of this article is to describe the scope of the problem, advances in pathophysiology, common clinical scenarios, and practical implementation of standard therapies for CHF. PMID- 11212859 TI - Rickets on the rise. PMID- 11212860 TI - Zona thinning with noncontact diode laser in patients aged < or = 37 years with no previous failure of implantation: a prospective randomized study. AB - PURPOSE: Zona thinning (ZT) is a technique used to improve pregnancy rates among patients > or = 38 years old and/or patients presenting previous implantation failure. The objective of the study was to determine whether ZT has a beneficial effect on patients younger than 37 years who are undergoing the first ICSI attempt. METHODS: A total of 103 patients submitted to ICSI for the first time and those aged < or = 37 years were divided in a prospective and randomized manner into two groups: group I, patients submitted to ZT (n = 51) (a laser diode with 1.48-micron wavelength (Fertilaser) was used for the procedure); group II, patients with no ZT (n = 52). In both groups, embryo transfer was performed on the second day. RESULTS: The age of group I patients (31.8 +/- 3.6) did not differ (P = 0.53) from that of group II patients (31.4 +/- 3.6). The number of metaphase II oocytes was similar (P = 0.76) for the two groups (group I = 9.12 +/ 5.27; group II = 8.67 +/- 5.02). The average number of embryos available per transfer of group I (6.14 +/- 4.02) did not differ (P = 0.69) from that of group II (5.75 +/- 3.83). The number of embryos transferred was similar (P = 0.61) for the two groups (group I = 2.76 +/- 0.9; group II = 2.87 +/- 0.79). The thickness of the zona pellucida of group I embryos (16.6 +/- 2.2 microns) did not differ (P = 0.08) from that of group II embryos (17.1 +/- 1.7 microns). The rate of embryo implantation (20.8%) and the rate of clinical pregnancy per embryo transfer (40.3%) were higher for group II than for group I (17.7% and 33.3%, respectively), but the difference was not significant (P = 0.55 and P = 0.54). CONCLUSIONS: These results suggest that ZT in the population aged < or = 37 years and with no previous failure of implantation may have no impact on intracytoplasmic sperm injection success rates. PMID- 11212861 TI - [GM2-activator protein and vesicular transport in the connecting cells of kidney collecting tubules]. PMID- 11212862 TI - [In memoriam Professor Dr. Hans Gunter Goslar, 1918-2000]. PMID- 11212863 TI - Expression of neural cell adhesion molecule in spinal cords following a complete transection. AB - Neural cell adhesion molecule (NCAM) regulates tissue organization during development and in the adult. NCAM upregulation occurs after an injury to brains and sciatic nerves. However, little is known about NCAM expression after spinal cord injury (SCI). By using a complete spinal cord transection with a 5 mm tissue removal, an increase in the NCAM level is detected in spinal cord stumps proximal and distal to the transection site at 1 d and 3 d post injury, while its expression at 8 d is declined to a lower level than that observed in sham operated spinal cords. The strong NCAM expression is present in motor neurons at 3 d post transection whereas the intensive NCAM immunostaining is localized in dorsal sensory and corticospinal fiber tracts at 8 d following injury. Collectively, NCAM level is elevated and strongly expressed in dorsal fiber tracts after SCI, implying that the endogenous process for spinal cord regeneration may take place after SCI. PMID- 11212865 TI - Intracerebroventricular injection of streptozotocin in rats produces both oxidative stress in the brain and cognitive impairment. AB - Recent reports suggest the involvement of free radicals in the pathophysiology of Alzheimer's disease [AD]. Streptozotocin [STZ] injection in the brain is known to cause cognitive impairment in rats and is likened to sporadic AD in humans. Though STZ is known to cause impairment in glucose and energy metabolism, it is not known whether this is associated with free radical generation. The present study was designed to investigate if the changes in learning and memory by intracerebroventricular administration of STZ are associated with changes in the markers of oxidative stress. Adult male Wistar rats [330-340 g] were injected with intracerebroventricular STZ [3 mg/kg] bilaterally stereotaxically under ketamine anesthesia [70 mg/kg]. The rats were treated with STZ twice, on day 1 and on day 3. The learning and memory behavior was analyzed using passive avoidance paradigms, elevated plus maze and the closed field activity test while the parameters of oxidative stress assessed were malondialdehyde [MDA] and glutathione. The behavioral tests were performed on day 17, 18 and 19. The rats developed significant deficits in learning, memory and cognitive behavior, indicated by deficits in passive avoidance paradigm and elevated plus maze as compared to sham rats. On day 21, the rats were sacrificed under ether anesthesia and the brains were analyzed for biochemical studies. There was a development of oxidative stress in the brain as indicated by significant elevations in malondialdehyde [MDA] levels and decreased levels of glutathione. The study demonstrates that intracerebroventricular STZ may be appropriate model for investigations of antioxidants as potential treatment in Alzheimer's dementia. PMID- 11212864 TI - Role of endogenous opioid peptides in protection of ischemic preconditioning in rat small intestine. AB - This study investigated the protective effects of ischemic preconditioning on intestinal ischemic injury and the role of endogenous opioid peptides (EOP) in these effects. Ischemia-reperfusion (I/R) induced by 30-min of ischemia and 60 min of reperfusion significantly increased the levels of malondialdehyde (MDA) and lactate dehydrogenase (LDH) and resulted in serious intestinal edema (wet weight/dry weight). The ischemic preconditioning (PC) elicited by three 8-min occlusion periods interspersed with 10-min reperfusion markedly attenuated intestinal injury caused by ischemia-reperfusion. Pretreatment with morphine (300 microg x kg(-1), i.v.) 10-min before ischemia and reperfusion mimicked the protection produced by PC. Naloxone (3 mg x kg(-1), i.v.) abolished the protection of morphine-induced preconditioning and ischemic preconditioning in rat intestine. However, there were no changes between naloxone alone and control groups. Treatment with naloxone before ischemia-reperfusion had no effect on animals compared with the I/R group. In addition, we also measured the content of endogenous opioid peptides (Leu-enkephalin) in the effluent which was collected before and during preconditioning. It was shown that the release of leu enkephalin was markedly increased during preconditioning. These results suggested that EOP might play an important role in PC in rat small intestine. PMID- 11212867 TI - Increase in hypoxanthine-guanine phosphoribosyl transferase gene mutations by exposure to electric field. AB - Previously, we reported that exposure to extremely low frequency magnetic field (400 mT) increased in hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene mutations. However, it is unclear these mutations were induced by magnetic field (MF), electric field (EF), or both. To explore this question, a new exposure apparatus for EF was manufactured. We observed an increase in HPRT gene mutations in Chinese hamster ovary (CHO) cells after exposure to EF (10 V/m, 60 Hz) for 10 h. The mutant frequency by EF-exposure was an approximate 2-fold of that by sham exposure. Our data suggest that the mutations induced by exposure of cells to the variable magnetic field at 400 mT may be, in part, due to the induced EF. PMID- 11212866 TI - The localization of dopamine D2 receptor mRNA in the human placenta and the anti angiogenic effect of apomorphine in the chorioallantoic membrane. AB - While there are some reports indicating that dopamine (DA) and D2-like receptors (Rc) are detected in human placenta, there is little evidence available regarding the function of DA or the precise localization of its receptors in this organ. In the present study, we confirmed the placental expression of DA D2 Rc transcripts by Northern blot analysis. Using in situ hybridization, we also first revealed that DA D2 Rc mRNA was expressed in cytotrophoblasts, syncytial trophoblasts, vascular endothelial cells, Hafbauer cells, and fibroblasts in the chorionic villi of the human placenta. The expression sites of DA D2 Rc mRNA led us to suspect other functions of DA in the placenta besides the regulation of human placental lactogen. Since the cells expressing DA D2 Rc mRNA are related to proliferation and remodeling of placental tissue, we tried to evaluate a possible involvement of DA in the regulation of placental angiogenesis. To this end, we used the chicken chorioallantoic membrane (CAM) assay. In CAM assay, apomorphine, a potent nonselective agonist of DA, has an anti-angiogenic effect. These results suggest that DA may regulate the vascularization of human placenta through its receptors present in the chorionic villi. PMID- 11212868 TI - Effect of ovarian hormones on intestinal mast cell reactivity to substance P. AB - Evidence exists to support the concept that ovarian hormones influence mast cell functioning and related events. Here, we evaluated the constitutive gender difference and the influence of ovarian status on rat mast cell (MC) distribution in jejunum and colon, histamine synthesis and/or its release elicited by Substance P (SP). Higher mast cell (MC) number and histamine release were found in female compared with male. In female rats, hormonal status did not affect the density of resident MC neither in the jejunum nor in the colon. Interestingly, histamine levels released after SP stimulation of jejunal segment was reduced in ovariectomized (OVX) compared with sham OVX rats, and restored in OVX female receiving progesterone. In the colon, OVX resulted in a significant increase in histamine levels released after SP stimulation and a treatment with progesterone did not restore basal histamine levels. Thus, ovarian steroid hormones do not affect jejunal and colonic mast cell number. However, the hormonal status differently influences jejunal and colonic MC sensitivity to SP. PMID- 11212869 TI - Vasomotion in rat mesentery during hemorrhagic hypotension. AB - Although vasomotion has been considered a feature of the microvascular bed under physiological conditions, it has also been observed following hypotension in several tissues. In this work, 158 mesenteric microvessels of 36 rats were investigated quantitatively in normovolemic and hemorrhaged animals, focussing on diameter changes, particularly vasomotion incidence and characteristics. The femoral arteries of Wistar rats (body weight BW = 188 +/- 23 g, mean +/- SD) anesthetized with pentobarbital were cannulated for arterial pressure (AP) monitoring and blood withdrawal. The protocol consisted of 15 min control and 30 min of hemorrhagic hypotension (AP = 52 +/- 5 mmHg, hemorrhaged vol. = 17 +/- 4 ml/kg BW). During control normovolemic conditions, analysis of mesenteric microcirculation using intravital videomicroscopy revealed neither arteriolar nor venular vasomotion. During hemorrhagic hypotension (HH) microvascular blood flow reduced to 25% of control. While venules did not show diameter changes during HH, arterioles contracted to 85 +/- 20% of control and arteriolar vasomotion appeared in 42% of the animals and 27% of the arterioles. The amplitude of arteriolar diameter change during HH relative to mean diameter and to control diameter averaged 65 +/- 24% (range: 32-129%) and 41 +/- 10% (range: 25-62%), respectively. Vasomotion analysis showed two major frequency components: 1.7 +/- 0.8 and 7.0 +/- 5.2 cycles/min. Arterioles showing vasomotion had a mean control diameter larger than the remaining arterioles and showed the largest constriction during HH. We conclude that hemorrhagic hypotension does not change venular diameter but induces arteriolar constriction and vasomotion in rat mesentery. This activity is expressed as slow waves with high amplitude and fast waves with low amplitude, and is dependent on vessel size. PMID- 11212870 TI - Regulation of bronchoalveolar lavage fluids cell function by the immunomodulatory agents from Cordyceps sinensis. AB - Cordyceps sinensis (C. sinensis) is one of the well known fungi used in traditional Chinese medicine for treatment asthma and bronchial and lung inflammation. In this study, effects of C. sinensis methanolic extracts on bronchoalveolar lavage fluids (BALF) cells proliferation, inflammatory cytokines production, and genes expression were evaluated. The proliferative response of BALF cells to lipopolysaccharide (LPS) was determined by the tritiated thymidine uptake method. The cell-free supernatants were harvested then tested for interlukin-1beta (IL-1beta), interlukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-12 (IL 12), and interferon-gamma (IFN-gamma) by the enzyme immunoassay. The results indicated that the CS-19-22 fraction dose dependently suppressed BALF cells proliferation activated by LPS. The CS-19-22 fraction also reduced IL-1beta, IL 6, IL-8, IL-10 and TNF-alpha production in LPS activated BALF cell cultures. Furthermore, the IL-12 and IFN-gamma production in activated BALF cells were enhanced by CS-19-22 treatment. The CS-19-22 fraction did not affect IL-1beta, IL 6, TNF-alpha, and IL-8 mRNAs expression in BALF cells detected by reverse transcription-polymerase chain reaction (RT-PCR). By contrast, the CS-19-22 fraction increased IL-12 and IFN-gamma mRNAs expression and decreased IL-10 mRNA expression in the BALF cells activated with LPS. These results indicated the CS 19-22 fraction suppressed IL-1beta, IL-6, TNF-alpha, and IL-8 cytokines production in BALF cells through other than inhibition of mRNAs expression pathway. These results also demonstrate that the therapeutic activity of C. sinensis in Chinese medicine may be related to modulation of TH1 and TH2 cells functions in bronchial airway. PMID- 11212871 TI - The effect of ketamine hydrochloride anesthesia on basal and N-methyl-D,L aspartate induced plasma prolactin secretion in the adult male rhesus monkey. AB - The excitatory amino acids (EAAs), glutamate and aspartate, acting predominantly on N-methyl-D-aspartate (NMDA) receptor, have been shown to be involved in the central regulation of the secretion of several anterior pituitary hormones including prolactin (PRL), whereas ketamine hydrochloride (KH), a widely used anesthetic, has been reported to antagonize a variety of NMDA receptor mediated actions of these EAAs. In the present study, the effect of KH on basal PRL levels as well as on N-methyl-D,L-aspartate (NMA), an agonist of NMDA receptor, induced plasma PRL secretion was investigated in the adult male rhesus monkey. The values were compared to those obtained from the same animals restrained in primate chairs. The plasma PRL concentrations were higher in animals receiving KH administered either intramuscularly (2.5 mg/kg BW at 30 min intervals) or intravenously (10 mg/kg BW) as compared to those observed in the unanesthetized chair-restrained monkeys. NMA induced an unequivocal increase in plasma PRL concentrations in both conscious chair-restrained and KH anesthetized monkeys, but the response was greater in anesthetized animals than the conscious monkeys. The present findings suggest that KH has stimulatory effects on both basal and NMA induced plasma PRL secretion. PMID- 11212872 TI - Significance of glutamate and dopamine neurons in the ventral pallidum in the expression of behavioral sensitization to amphetamine. AB - To explore the significance of ventral pallidum (VP) during the amphetamine sensitization, we first investigated if there are neurochemical alterations in the VP during amphetamine withdrawal period. Chronic amphetamine-treated (5 mg/kg x 14 days) rats displayed an apparent locomotion sensitization as compared with saline controls when challenged with 2 mg/kg amphetamine at withdrawal days 10 14. A microdialysis analysis revealed that output of the dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, in the VP of amphetamine sensitized rats increased approximately two-fold as compared to controls at both pre- and post-amphetamine challenge period. On the other hand, the in vivo glutamate output in the VP increased upon amphetamine challenge in the behaviorally sensitized rats, but not in the controls. To evaluate if drug manipulation in the VP would affect the behavioral sensitization, we treated both groups of rats with NMDA receptor antagonist, MK-801 (5 microg/microl for 5 days; bilateral) in the VP during withdrawal days 6-10. Animals were challenged with 2 mg/kg amphetamine at withdrawal day 11. The behavioral profile exhibited that MK 801 pre-treatment significantly blocked the locomotion hyperactivity in amphetamine-sensitized rats. Taken together, the current results suggest that the excitatory amino acid in the VP plays a significant role during the expression of behavioral sensitization to amphetamine. PMID- 11212873 TI - Viral neuroinvasion as a marker for BBB integrity following exposure to cholinesterase inhibitors. AB - Exposure to the nerve agent soman, an irreversible cholinesterase (ChE) inhibitor, results in changes in blood-brain barrier permeability attributed to its seizure-induced activity. However, smaller BBB changes may be independent of convulsions. Such minor injury may escape detection. A nonneuroinvasive neurovirulent Sindbis virus strain (SVN) was used as a marker for BBB permeability. Peripheral inoculation of mice with 2 x 10(3) plaque forming units (PFU) caused up to 10(5) PFU/ml viremia after 24 hours with no signs of central nervous system (CNS) infection and with no virus detected in brain tissue. Intra cerebral injection of as low as 1-5 PFU of the same virus caused CNS infection, exhibited 5-7 days later as hind limb paralysis and death. Soman (0.1-0.7 of the LD50) was administered at peak viremia (1 day following peripheral inoculation). Sublethal soman exposure at as low as 0.1 LD50 resulted in CNS infection 6-8 days following inoculation in 30-40% of the mice. High virus titer were recorded in brain tissue of sick mice while no virus was detected in healthy mice subjected to the same treatment. No changes in the level of viremia or changes in viral traits were observed in the infected mice. The reversible anticholinesterases physostigmine (0.2 mg/kg, s.c.) and pyridostigmine (0.4 mg/kg, i.m.) injected at a dose equal to 0.1 LD50, induced similar results. Thus, both central and peripheral anticholinesterases (anti-ChEs) induce changes in BBB permeability sufficient to allow, at least in some of the mice, the invasion of this otherwise noninvasive but highly neurovirulent virus. This BBB change is probably due to the presence of cholinesterases in the capillary wall. SVN brain invasion served here as a highly sensitive and reliable marker for BBB integrity. PMID- 11212874 TI - Generation of polyclonal antiserum against the growth hormone secretagogue receptor (GHS-R): evidence that the GHS-R exists in the hypothalamus, pituitary and stomach of rats. AB - Growth hormone (GH) secretagogues (GHSs), which stimulate GH secretion, are synthetic compounds that act through the GHS receptor (GHS-R) which has been recently cloned. We raised an antiserum in a rabbit against a synthetic peptide corresponding to amino acid residues 248-260 of the third intracellular loop of the rat GHS-R. A competitive immunoassay showed that the antiserum had a specific affinity for the target peptide. To confirm the specificity of the antiserum, the GHS-R cDNA was stably expressed in COS-7 cells. In Western blot analysis, the band was detected at 44 kDa in the extracts from COS-7 cells expressing GHS-R (COS-7/tf3-2) but not in those from wild-type COS-7 cells. Furthermore, while COS 7/tf3-2 cells were strongly immunostained for GHS-R, no GHS-R-like immunoreactivity was observed in wild-type COS-7 cells. Immunoreactive bands were also observed at approximately 46 kDa in the extracts from rat hypothalamus, pituitary and stomach by Western blot analysis. These studies are the first to show the existence of GHS-R protein in the stomach. The antiserum for the GHS-R is sensitive and specific, and it would be useful for clarifying the roles of GHS/ghrelin. PMID- 11212875 TI - Linoleamide, a brain lipid that induces sleep, increases cytosolic Ca2+ levels in MDCK renal tubular cells. AB - Linoleamide is an endogenous lipid that has been shown to induce sleep in cats, rats and humans. However, its physiological function remains unclear. In this study the effect of linoleamide on cytosolic free Ca2+ concentrations ([Ca2+]i) in Madin Darby canine kidney (MDCK) tubular cells was examined, by using fura-2 as a Ca2+ probe. In a concentration-dependent manner, linoleamide induced increases in [Ca2+]i between 10-500 microM with an EC50 of 20 microM. The signal comprised a slow rise and a persistent phase, and was a result of internal Ca2+ release and external Ca2+ influx because it was partly inhibited by external Ca2+ removal. In Ca2+-free medium, depletion of the endoplasmic reticulum Ca2+ store with 1 microM thapsigargin abolished 100 microM linoleamide-induced internal Ca2+ release, and conversely, pretreatment with linoleamide prevented thapsigargin from releasing internal Ca2+. This demonstrates that the internal source of linoleamide-induced [Ca2+]i increase is located in the endoplasmic reticulum. This discharge of internal Ca2+ caused capacitative Ca2+ entry because after incubation with 100 microM linoleamide in Ca2+-free medium for 8 min readmission of 3 mM CaCl2 induced increases in [Ca2+]i. After the formation of inositol-1,4,5 trisphosphate (IP3) was blocked by the phospholipase C inhibitor U73122 (1 microM), linoleamide still induced an increase in [Ca2+]i but the shape of the increase was altered. Similar results were found for another sleep-inducing lipid 9,10-octadecenoamide. Together, the present study shows that the endogenous sleep inducing lipid linoleamide was able to cause significant increases in [Ca2+]i in renal tubular cells, by releasing the endoplasmic reticulum Ca2+ store and triggering capacitative Ca2+ entry in a manner independent of IP3. PMID- 11212876 TI - Hyperthermia in oncology. AB - The purpose of this article is to provide an overview on the current clinical application of hyperthermia combined with conventional treatment modalities (e.g. ionizing radiation, chemotherapy) in the treatment of malignant disease. The clinical application of hyperthermia with increase of tissue temperatures (range 40-44 degrees C) has been integrated in multimodal anti-cancer strategies. This review describes selected phase I or II (n = 17) and phase III trials (n = 16) investigating the effect of hyperthermia combined with radiotherapy (n = 10 trials), chemotherapy (n = 15 trials), or both (n = 8 trials) in a total of more than 2200 patients. The trials were performed in a variety of solid tumours (e.g. melanoma, head and neck cancer, breast cancer, cancer of the gastrointestinal or urogenital tract, glioblastoma, sarcoma) in paediatric or adult patients. Profound research has produced a scientific basis for the simultaneous application of hyperthermia in combination with ionizing radiation and/or systemic chemotherapy. Hyperthermia is becoming more accepted clinically, due to the substantial technical improvements made in achieving selected increase of temperatures in superficial and deep-seated tumours. At present, the combination of hyperthermia and chemotherapy or radiochemotherapy is further tested within clinical protocols (phase II/III) in order to improve local tumour control and relapse-free survival in patients with high-risk or advanced tumours of different entities. PMID- 11212877 TI - Whole-body hyperthermia with water-filtered infrared radiation: technical physical aspects and clinical experiences. AB - Among the different methods of whole-body hyperthermia (WBH), the energy transfer with infrared radiation seems to have established itself as a relatively simple procedure. The infrared systems differ with regard to the used spectrum of radiation. In the case of water-filtered infrared radiation, infrared A (760-1400 nm) is the focal point of heat radiation. This radiation penetrates deep into the skin up to the capillary area of the corium. Eighty treatments of patients in an advanced stage of cancer (40 male, 40 female, April 1998-April 1999) were performed with a WBH device with water-filtered infrared radiation, IRATHERM 2000. Extreme WBH was combined with induced hyperglycaemia and relative hyperoxaemia, and for 83% of the patients with chemotherapy as well. The body core temperature was measured rectally (85%) or vesically. The objectives of the thermal control were a low rate of side-effects and a quick rise of the body-core temperature with regard to the condition of the patient's skin. The mean duration of the rising phase (37.5-41.5 degrees C) was 87 +/- 19 min. A correlation between lamp power and rising time (r = 0.08) was not found. Moreover, no correlation could be found between the appearance of thermal lesions > or = WHO 2nd degree and the lamp power. Thermal lesions according to WHO 1st, 2nd and 3rd degrees appeared in the case of 20, 15 and one treatment, respectively. Their area amounted in 2nd-degree cases to 0.08% of the body surface, on average. The highest mean temperature over 60 min (T60) was 42.1 +/- 0.1 degrees C, and the mean of maximum temperature (Tmax) was 42.3 +/- 0.1 degrees C. The mean thermal isoeffect dose EM43 was 35.8 +/- 6.3 min. WBH with water-filtered infrared radiation in combination with induced hyperglycaemia and relative hyperoxaemia (procedure of systemic Cancer Multistep Therapy) is a safe and practicable procedure with good tolerability in the case of experienced application. It permits a rapid rise of body-core temperature and a high thermal constancy in the plateau phase. An all-around access to the patient is possible in all therapy phases. PMID- 11212878 TI - Feasibility and patient tolerance of a novel transrectal ultrasound hyperthermia system for treatment of prostate cancer. AB - This report describes patient tolerance and toxicity of a transrectal ultrasound hyperthermia system used with external beam radiation therapy in treatment of locally advanced prostate cancer. Nine patients with clinical T2B-T3B (4th edition AJCC criteria) disease received external beam radiation therapy, with two hyperthermia treatments scheduled at least 1 week apart during the first 4 weeks of radiation. Five patients also received hormonal therapy. Interstitial and anterior rectal wall thermometry were performed. Median temperature for each treatment (T50) was 40.8 degrees C and mean CEM T90 = 43 degrees C was 3.4 min. Rectal wall temperature was maintained at < or = 40 degrees C. Treatment duration was limited in three of 17 sessions due to positional discomfort which was alleviated with light IV sedation and use of a 'New Life' mattress (Comfortex, Inc. Winoba, MN, USA). Acute toxicity was limited to NCI common toxicity criteria grade 1 and no excess toxicity was noted with full course radiation therapy +/- hormonal therapy. These findings are consistent with those reported in a previous phase I trial assessing this device. Given the favourable toxicity profile demonstrated to date, modification of treatment parameters for this ongoing phase II study have been instituted that should further the efficacy of transrectal ultrasound hyperthermia for treatment of prostate cancer. PMID- 11212879 TI - Adenoviral p53 gene therapy promotes heat-induced apoptosis in a nasopharyngeal carcinoma cell line. AB - BACKGROUND: It has previously been demonstrated that Ad5CMV-p53 gene transfer, either used alone or delivered concomitantly with ionizing radiation, resulted in cytotoxicity mediated by apoptosis in nasopharyngeal carcinoma (NPC) cell lines. In this study, a novel approach was evaluated of combining Ad5CMV-p53 gene therapy with hyperthermia (HT), in the CNE-1 NPC cell line, which harbours a mutation in codon 249 of the p53 gene. MATERIALS AND METHODS: CNE-1 cells were infected using either Ad5CMV-p53 or Ad5CMV-B-gal, followed, 24 h later, by HT (43 degrees C x 0-2 h). Protein was extracted for Western blot analysis, and apoptosis was evaluated using acridine-orange ethidium bromide staining, followed immediately by fluorescent microscopy examination for the proportion of cells displaying morphologic features of apoptosis. RESULTS: Ad5CMV-p53 gene therapy combined with HT resulted in a dose-dependent cytotoxicity with less than 1% clonogenic survival when 10 pfu/cell of Ad5CMV-p53 was combined with 2 h heating at 43 degrees C. Western blotting demonstrated that treatment with Ad5CMV-p53 resulted in the rapid expression of p53, which was minimally affected by HT. The inducible form of hsp70 was maximally expressed at 48 h post-HT, with minimal effect when cells were additionally treated with Ad5CMV-p53. Clonogenic cytotoxicity was associated with the development of apoptosis, with up to 70% of CNE-1 cells displaying morphologic features of apoptosis after the combination treatments. CONCLUSION: Based on the shapes of the clonogenic survival curves, Ad5CMV-p53 gene therapy and HT appear to interact in an additive manner, suggesting the therapeutic potential of this combined treatment approach for patients with NPC. PMID- 11212880 TI - Dosimetry and techniques for simultaneous hyperthermia and external beam radiation therapy. AB - An increased biological effect is realized when hyperthermia and radiation therapy are combined simultaneously. To take advantage of this effect, techniques have been developed that combine existing hyperthermia devices with a linear accelerator. This allows concomitant delivery of either ultrasound or microwave hyperthermia with photon radiation therapy. Two techniques have been used clinically: the orthogonal technique, in which the microwave or ultrasound beam and the radiation beam are orthogonal to one another, and the en face technique, in which the ultrasound or microwave beam and the radiation beam travel into the tumour through the same treatment window. The en face technique has necessitated the development of special attachments so that the hyperthermia device can be mounted to the linear accelerator and so that non-uniform portions of the hyperthermia device can be removed from the radiation beam. For microwave therapy, applicators are mounted onto the linear accelerator using the compensating filter tray holder. For ultrasound, special reflector devices are mounted to a frame that is mounted onto the compensating filter tray holder of the linear accelerator. Because the linear accelerator is an isocentric device, the height of the radiation source is fixed, and this has necessitated specially designed devices so that the ultrasound support system is compatible with the linear accelerator. The treatment setups for both the en face technique and the orthogonal technique require the interaction of both hyperthermia and radiation therapy personnel and equipment. The dosimetry and day-to-day operations for each technique are unique. The simulation for the en face technique is much different from the simulation of a normal radiation treatment and requires the presence of a hyperthermia physicist. Also, for the en face technique, the attenuation of the microwave applicator and the thickness and attenuation of the ultrasound reflector system are taken into account for radiation dosimetry. This paper presents details of the dosimetry and logistics of the techniques for simultaneous thermoradiotherapy based on 7 years of experience treating more than 50 patients. PMID- 11212881 TI - RF hyperthermia array modelling; validation by means of measured EM-field distributions. AB - The accuracy of a hyperthermia treatment simulation determines its role in prospective treatment planning and dosimetry for the individual patient. Of importance are (1) the accuracy of the numerical simulation method, and (2) the numerical description of the hyperthermia treatment system. The accuracy of the numerical method is generally determined by analysis of a problem that is analytically solvable. The validity of the description of the hyperthermia system is to be investigated by comparison of the simulated and measured EM-field amplitude and phase of the clinical operational hyperthermia system. In this paper, the numerical description of the AMC-4 waveguide phased array for which treatment planning is performed by the Weak Form of the Conjugate Gradient FFT method is investigated. The accuracy of the description is analysed for four set ups, varying the bolus size and the number of waveguides attached to a phantom. The comparison of experimental and numerical data has demonstrated the ability of the Weak Formulation of the Conjugate Gradient FFT method to predict the EM-field of the AMC-4 waveguide array hyperthermia system, including effects due to bolus size variations. However, based on the comparison of the measured EM-field distributions and those obtained from simulations, the accuracy of the planning system is found to be insufficient for quantitative SAR dosimetry for individual patients. Qualitative SAR dosimetry can be applied in cases where the accuracy is of minor importance, e.g. for the retrospective analysis of problematic hyperthermia treatments. Prospective applications of the treatment planning system include the (qualitative) determination/simulation of a set of starting points giving a 'close to optimal' amplitude and phase setting, the prediction of possible problem areas and the analysis of the performance of new/improved hyperthermia devices. PMID- 11212882 TI - Theoretical comparison of the SAR distributions from arrays of modified current sheet applicators with that of lucite cone applicators using Gaussian beam modelling. AB - The technical comparison of Current Sheet Applicator (CSA) and Lucite Cone Applicator (LCA) arrays covering an area of approximately 20 x 20 cm2 is investigated based on Gaussian beam (GB) predicted SAR distributions. The comparison is made in muscle equivalent tissue at 1 cm depth (maximum SAR normalized to 100%) and over a volume of 3 cm depth under the aperture of the antennae. The planar SAR distribution is tested on field sizes (FSx: area covering x% SAR), penetration depth (PD) and homogeneity coefficient (HC = FS75/FS25). From the SAR volume, a SAR-Volume histogram (volume enclosing y% SAR/total volume) is calculated as well as the volumetric HC. First, the prototype CSA (aperture 58 x 67 mm2, FS50 = 21 cm2) is technically modified to assure clinical safety and load independence. The modified CSA, the D-CSA, has an aperture of 66 x 75 mm2 with an FS50 = 28 cm2 and a PD of 10 mm, the LCA (aperture 105 x 105 mm2) has an FS50 = 76 cm2 and PD = 12 mm. The HC equals 0.21 (D-CSA), respectively 0.22 (LCA). Secondly, a 3 x 3 D-CSA array is compared with a 2 x 2 LCA array. The FS50s equals 72% (D-CSA), respectively 75% (LCA). The SAR volume histograms, planar and volumetric HC show no significant difference; however, the planar HCs for D-CSA and LCA increase from 0.2-0.3, indicating that incoherently powered arrays from these antennae build SAR distributions constructively. PMID- 11212883 TI - Demystified...adhesion molecule deficiencies. AB - The basic physiology of leucocyte emigration from the intravascular space into the tissues is now known to be dependent on a class of cell surface molecules that have come to be known as adhesion molecules. Many cell-cell interactions are dependent on adhesion and signal transduction via the various adhesion molecules, particularly the integrins. The study of the functions of these molecules has been enhanced by the development of blocking and activating monoclonal antibodies, knockout mice, and by the rare "experiments of nature" in the human population, in whom there is absence or dysfunction of one of the adhesion molecules. This review describes these leucocyte adhesion defects and discusses how they have provided important insights into the function of these molecules. PMID- 11212884 TI - Correlation between apoptosis microarray gene expression profiling and histopathological lymph node lesions. AB - AIMS: Microarray technology has recently led to the identification of molecular prognostic subgroups in non-Hodgkin's lymphomas. To determine the usefulness of ready made macroarrays as routine diagnostic tools in haematopathology, lymph node biopsies were analysed using a cDNA macroarray containing genes involved in apoptosis, including caspases. METHODS: Nine biopsy specimens were analysed using total frozen tissues: four samples of B cell follicular lymphoma, two of B cell diffuse large cell lymphoma, and three of non-neoplastic lymph nodes from benign lymphadenitis. Nine cell populations were sorted from fresh tissues: malignant B cells from two patients with follicular lymphoma and two with diffuse large cell lymphoma, reactive B cells from two benign lymph nodes, reactive T cells from one benign lymph node, and virgin (mantle zone) B cells and germinal centre B cells from benign tonsils. Immunohistochemistry (IHC) on paraffin wax sections was performed for the localisation of caspases 2, 3, 4, 7, 8, and 9. RESULTS: In the clustered array data, sorted cells from samples sharing common histological lesions were grouped together, whereas the array/histology correlation was less satisfactory for tissues. The expression profiles of both the array and IHC methods correlated for most caspases and samples. CONCLUSIONS: Variations in array profiles of sorted cell populations can be associated with specific histological features, suggesting a possible diagnostic application of ready made apoptosis macroarrays in haematopathology. PMID- 11212885 TI - Rapid real time PCR to distinguish between high risk human papillomavirus types 16 and 18. AB - AIMS: To assess the validity and practicality of real time polymerase chain reaction (PCR) for human papillomavirus (HPV) testing in combination with liquid based cytology samples for cervical screening. METHODS: Real time PCR using consensus (GPS+/6+) and type specific primers was developed to detect genital HPV types. This provides rapid, efficient amplification followed by denaturation of the product and computer analysis of the kinetics data that are generated. Liquid based cytology samples were obtained from patients attending routine cervical screening clinics. DNA was extracted from the residual cellular suspension after cytology using spin columns. RESULTS: Real time PCR successfully distinguished between HPV-16 and HPV-18 on the basis of amplification with consensus primers followed by DNA melting temperature (Tm) analysis. Sensitivities of one to 10 copies of HPV-16 (mean Tm = 79.4 degrees C; 2 SD, 0.8) and four to 40 copies of HPV-18 (mean Tm = 80.4 degrees C; 2 SD, 0.4) were obtained. In a mixed population of SiHa and HeLa cells containing known copy numbers of HPV-16 and HPV-18 genomes, HPV-16 and HPV-18 products were clearly separated by Tm analysis in mixtures varying from equivalence to 111000. Together with detailed melt analysis, type specific primers from the same region of the L1 gene confirmed the differential ability of this system. The method was applied to 100 liquid based cytology samples where HPV status using conventional GP5+/6+ PCR was already known. There was 95% agreement between the methods, with 55 positives detected by conventional PCR and 59 with real time PCR. The method was then tested on 200 routine liquid based cytology samples. Approximately 10% were positive by real time PCR, most of which were classified as HPV-16 by detailed melt analysis. Thirteen (6.8%) HPV positives were identified in 189 samples showing no evidence of cervical cytological abnormality. CONCLUSIONS: Real time PCR is a rapid, efficient method for the detection of HPV with the separation of HPV-16 and HPV 18 on the basis of differential Tm. Preliminary results suggest it could prove PMID- 11212886 TI - Insulin-like growth factors I and II induce cell death in Wilms's tumour cells. AB - AIM: To study the effects of insulin-like growth factors (IGFs) on the growth phenotype of a Wilms's tumour cell line (WCCS-1). METHODS: WCCS-1 cells were cultured in vitro and exposed to IGF-I and IGF-II, as well as their antagonists, IGF binding protein 2 and the type I receptor blocking antibody IGF-IRalpha. The effects on proliferation and cell cycle parameters were assayed by assessing cell numbers, autoradiography after labelling with tritiated thymidine, and flow cytometry after double staining with fluorescein isothiocyanate (FITC) labelled annexin V and propidium iodide. RESULTS: The addition of IGF-I as well as IGF-II in physiological doses induced cell death in Wilms's tumour cells. Cell numbers decreased most dramatically on the fifth to sixth day after growth factor addition. The occurrence of apoptosis as well as necrosis was confirmed by annexin-V staining of cell cultures. S-phase indices were comparable, irrespective of whether the cells were exposed to IGFs or not, which suggests that WCCS-1 cells undergo cell death at random during the cell cycle rather that from the prereplicative phase. To exclude any influences of the IGF binding proteins (IGFBPs), all results were repeated with Des(1-3)IGF-I, which is unable to bind to any of the IGFBPs. However, this peptide was equally potent in inducing cell death. Finally, the addition of IGFBP-2 or the type 1 receptor blocking antibody IGF-IRalpha partly abrogated the death inducing effects of IGF I and IGF-II. CONCLUSIONS: Insulin like growth factors induce cell death- apoptosis as well as necrosis--in cultured Wilms's tumour cells. Furthermore, it is proposed that this effect is mediated by the type 1 receptor. PMID- 11212887 TI - The University of Halle through the centuries. PMID- 11212888 TI - Microarrays under the microscope. AB - Microarray technology is a rapidly advancing area, which is gaining popularity in many biological disciplines from drug target identification to predictive toxicology. Over the past few years, there has been a dramatic increase in the number of methods and techniques available for carrying out this form of gene expression analysis. The techniques and associated peripherals, such as slide types, deposition methods, robotics, and scanning equipment, are undergoing constant improvement, helping to drive the technology forward in terms of robustness and ease of use. These rapid developments, combined with the number of options available and the associated hyperbole, can prove daunting for the new user. This review aims to guide the researcher through the various steps of conducting microarray experiments, from initial strategy to analysing the data, with critical examination of the benefits and disadvantages along the way. PMID- 11212889 TI - Meeting report: Dictyostelium 2000: a conference on the cell and developmental biology of a social amoeba, Dundee, Scotland, July 30-August 4, 2000. PMID- 11212890 TI - Meeting report: XIIIth meeting of the International Society for Evolutionary Protistology, Ceske Budejovice, Czech Republic, July 31-August 4, 2000. PMID- 11212891 TI - Opinion: long branch attraction and protist phylogeny. PMID- 11212892 TI - Bacterial orthologues indicate the malarial plastid gene ycf24 is essential. AB - ycf24 is a well conserved gene found in all major groups of bacteria, as well as on red algal plastid genomes and the vestigal plastid genome of apicomplexan pathogens like the malaria parasite Plasmodium falciparum (ORF470). Some database annotations describe Ycf24 as an ABC transporter subunit, but we find the level of significance is low. To investigate ycf24's function we disrupted it in the cyanobacterium Synechocystis sp., strain PCC6803 which has a multi-copy genome. This showed ycf24 is essential, partial loss producing a terminal phenotype of chlorosis, reduced cell size, loss of DNA, and a striking arrest in cytokinesis. Attempts to disrupt the single copy of ycf24 in E. coli failed to give stable transformants. When Ycf24 was over-expressed in E. coli as a soluble fusion protein, it localized mostly as a band on either side of the nucleoid and nucleoid partitioning was aberrant. We propose the relict plastid organelle of apicomplexans retains its capacity for protein synthesis because Ycf24 is essential. PMID- 11212893 TI - Molecular phylogeny of Besnoitia and the genetic relationships among Besnoitia of cattle, wildebeest and goats. AB - Knowledge on parasites of the genus Besnoitia is sparse, which are classified in the subfamily Toxoplasmatinae of the phylum Apicomplexa. This arrangement hypotheses that Besnoitia represents the sister group to species such as Toxoplasma gondii and Hammondia hammondi. In order to test this hypothesis, phylogenetic analyses of 18S ribosomal DNA (rDNA) from Besnoitia, Hammondia, Isospora, Frenkelia, Eimeria, Neospora, Sarcocystis and Toxoplasma were performed. The 18S rDNA of Besnoitia besnoiti, Besnoitia jellisoni and Eimeria alabamensis were amplified by PCR and sequenced. Phylogenetic analyses by parsimony and maximum-likelihood methods showed Besnoitia to be reproducibly the sister group to a clade containing Hammondia, Neospora and Toxoplasma. Furthermore, Besnoitia of cattle, wildebeest and goats had identical ITS1 rDNA sequences, which questions the use of the taxon Besnoitia caprae to describe the Besnoitia found in goats. PMID- 11212894 TI - Phylogenetic position of Cryothecomonas inferred from nuclear-encoded small subunit ribosomal RNA. AB - The systematic position of the genus Cryothecomonas has been determined from an analysis of the nuclear-encoded small subunit ribosomal RNA gene of Cryothecomonas longipes and two strains of Cryothecomonas aestivalis. Our phylogenetic trees inferred from maximum likelihood, distance and maximum parsimony methods robustly show that the genus Cryothecomonas clusters within the phylum Cercozoa, and is related to the sarcomonad flagellate Heteromita globosa. Morphological data supporting the taxonomic placement of Cryothecomonas near the sarcomonad flagellates has been compiled from the literature. The high number of nucleotide substitutions found between two morphologically indistinguishable strains of Cryothecomonas aestivalis suggests the possibility of cryptic species within Cryothecomonas aestivalis. PMID- 11212895 TI - Complete gene map of the plastid genome of the nonphotosynthetic euglenoid flagellate Astasia longa. AB - Astasia longa is a colourless heterotrophic flagellate closely related to the photoautotrophic Euglena gracilis. A circular 73 kb plastid DNA (ptDNA) has been isolated from A. longa that is about half the size of the chloroplast DNA of E. gracilis (143 kb). We have determined the complete sequence of the ptDNA of A. longa and established a complete gene map. All chloroplast genes for photosynthesis-related proteins are completely absent from the A. longa plastid DNA except for rbcL, the gene for the ribulose-1,5-bisphosphate carboxylase large subunit. Identified genes encode components of the plastid transcriptional and translational machinery: genes for three subunits of a chloroplast RNA polymerase, 20 chloroplast ribosomal protein genes, a gene for a plastid elongation factor Tu, 27 plastidic tRNA genes and three tandemly arranged repeats of 16S, 23S and 5S rDNA. Transcripts of a number of genes were detected by Northern hybridisation. The ribulose-1,5-bisphosphate carboxylase large subunit protein has been identified by immunoblotting. PMID- 11212896 TI - A problem cannot be solved unless one sees it (F. Schmitz 1883). Lothar geitler (1899-1990) and the endosymbionts: revolutionary as a twen, conservative till ripe old age. PMID- 11212897 TI - Frequent loss of heterozygosity at the 19p13.3 locus without LKB1/STK11 mutations in human carcinoma metastases to the brain. AB - Inactivating germline mutations of the novel putative tumor-suppressor gene LKB1/STK11 at 19p13.3 have been shown to cause Peutz-Jeghers syndrome (PJS), an autosomal dominantly inherited disease characterized by a predisposition to mucocutaneous pigmentations, as well as various benign and malignant neoplasms. To elucidate the role of LKB1/STK11 in the carcinogenesis of primary and secondary human brain tumors, a total of 309 tumors were analyzed for loss of heterozygosity (LOH) at microsatellite loci D19S886, DI9S878, and D19S565. Low LOH rates were observed for glioma (17.3%, n = 139), meningioma (5.3%, n = 57), schwannoma (0%, n = 21), pituitary adenoma (18.8%, n = 16), primary CNS lymphoma, neuroblastoma, plasmocytoma, medulloblastoma, germinoma, and papilloma of the choroid plexus (6.6%, n = 15). In contrast, brain metastases exhibited a mean LOH frequency of 42.6% (n = 61), with breast (56.3%) and lung cancer metastases (58.3%) being most frequently affected. Genomic DNA sequencing of the complete coding region of LKB1/STK11 was performed in all brain metastases exhibiting LOH (n = 26); no mutation was revealed, but we did find a germline mutation in a PJS patient. Despite high LOH fiequencies at the 19p13.3 locus in carcinoma metastases to the brain and occasional mutations reported for certain primary carcinomas, there are no mutations in LKB1/STK11. This fact suggests that alterations of LKB1/STK11 occur relatively early in tumorigenesis and are rarely involved in the development of carcinoma metastases. Based on these findings, the genes adjacent to LKB1/STK11 may be relevant for the development of metastases to the brain from certain carcinomas. PMID- 11212898 TI - Analysis of mdm2 and p53 gene alterations in glioblastomas and its correlation with clinical factors. AB - Malignant gliomas are the most frequent primary brain tumors. Recent studies defined several genetic markers, which might characterize molecular-biological subsets of glioblastomas with probably prognostic implications. To elucidate the involvement of murine-double-minute (mdm)2 gene amplifications and mutations of the tumor suppressor gene p53 in the tumorigenesis of malignant gliomas we analyzed a series of 75 glioblastomas. The p53 mutations occur in one-third of glioblastomas, mdm2 amplifications were found in 13% of cases. Our analysis revealed a hot spot in the p53 gene locus in codon 156, the same point mutation was detected in 4 tumor samples. None of the mdm2 amplified tumors had p53 mutations, supporting the hypothesis, that mdm2 amplifications are alternative mechanisms for p53 inactivation. Patients with p53 mutated tumors were significantly younger characterized by a mean age of 44 years. Additionally association with longer overall survival could be detected for this subgroup of patients. In our study, survival estimation revealed a significant correlation of mdm2 gene amplification with shorter survival time, and support the hypothesis, that mdm2 oncogene activation appears to occur late in tumor progression and may be characteristic as negative prognostic marker. PMID- 11212899 TI - Cranial nerve root entry zone primary cerebellopontine angle gliomas: a rare and poorly recognized subset of extraparenchymal tumors. AB - With the exception of patients with neurofibromatosis type II, pediatric extraparenchymal cerebellopontine angle (CPA) tumors of any sort are extremely rare. Most gliomas encountered in the CPA in either children or adults involve the CPA as exophytic extensions of primary brain stem and/or cerebellar tumors. We encountered an unusual case of a giant CPA pilocytic astrocytoma arising from the proximal trigeminal nerve, completely separate from the brain stem. A nine year-old girl with no evidence for any neurocutaneous syndrome, presented with headaches, mild obstructive hydrocephalus, trigeminal hypesthesia and a subtle peripheral facial paresis. Pre-operative neuroimaging suggested a petroclival meningioma. The tumor was completely resected via a right pre-sigmoid, retro labyrinthine, subtemporal, transtentorial ('petrosal') approach, using intraoperative neurophysiological monitoring, with minimal morbidity. This appears to be the first reported case of a pediatric primary CPA glioma and the seventh reported case of primary CPA glioma, overall. It represents the second reported case of a primary CPA pilocytic astrocytoma. Given the findings in this case and the six other cases of primary CPA gliomas reported in the literature, as well as the results of histological studies of normal cranial nerves, we hypothesize that the point of origin of these rare and unusual tumors is the root entry zone of the involved cranial nerves. The differential diagnosis of primary CPA tumors should be expanded to include cranial nerve root entry zone primary CPA gliomas. PMID- 11212900 TI - A phase II study of nimustine hydrochloride, cisplatin, and etoposide combination chemotherapy for supratentorial malignant gliomas. AB - Twenty-eight patients who were previously treated by aggressive surgery and radiation and were diagnosed with supratentorial malignant gliomas received a combination of nimustine hydrochloride; 1-(4-amino-2-methyl-5-pyrimidinyl) methyl 3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), cisplatin and etoposide (ACE therapy) as primary treatment. Cisplatin and etoposide were given at doses of 20 and 60 mg/m2/day for 5 days, respectively, ACNU doses 80 mg/m2/day on the first day. Treatment was repeated at 4-week intervals for up to 3 cycles. Seventeen patients (60.7%) complained of nausea. Grade 3 or 4 hematological toxicity occurred in 11 patients (39.3%), and grade 3 or 4 renal toxicity occurred in 2 patients. The percentage of patients who showed complete or partial response was 28.6% (8/28). The median time of tumor progression was 40 weeks, and the median survival time was 146 weeks. There were some long-surviving patients who may have benefited from ACE combination. This study demonstrated the effects of ACE combination in patients with supratentorial malignant gliomas. PMID- 11212902 TI - Treosulfan chemotherapy for recurrent malignant glioma. AB - Treosulfan is a bifunctional alkylating prodrug with activity against various solid tumors. To improve the outcome for patients with recurrent malignant glioma, we assessed the efficacy of intravenous treosulfan (6-10 g/m2 4-weekly) as salvage therapy for patients with recurrent or progressive glioblastoma (GB, n = 14) or anaplastic astrocytoma (AA, n = 2). All patients had prior involved field radiotherapy and adjuvant nitrosourea-based chemotherapy. A total of 56 cycles were administered. Tumor responses were assessed radiologically and clinically prior to each cycle. All patients were assessable for toxicity, response and survival. There were no complete or partial responses (CR, PR). Two patients progressed after the first cycle, 14 patients had initially stable disease (SD). Median progression-free survival was 3.25 months for the GB patients. Five patients were progression-free at 6 months (30%), including the 2 AA patients. The 2 AA patients are stable at 22 months. Myelosuppression was the dose-limiting toxicity in this cohort of nitrosourea-pretreated patients. Treosulfan has modest activity in patients with recurrent malignant glioma. Further evaluation of treosulfan in chemonaive malignant glioma patients is warranted. PMID- 11212901 TI - Angiolipomas of the central nervous system. AB - Angiolipomas are neoplasms composed of mature adipocytes admixed with abnormal vascular elements. They are most commonly found in the subcutaneous tissue of the trunk and extremities, but other sites have been reported. The craniospinal axis is an uncommon but significant site. An extensive review of the literature is conducted. We summarize 94 cases of angiolipomas in the central nervous system (CNS) in 92 patients, including five in our own series, to highlight the most prominent features of these tumors. The increasing number of cases of CNS angiolipoma in the era of magnetic resonance imaging raises the question of the rarity of these lesions. PMID- 11212903 TI - Allocentric visuospatial processing in patients with cerebral gliomas: a neurocognitive assessment. AB - Visuospatial function is a central neuropsychological domain which has been neglected in brain tumor studies. This study examined visuospatial function in 4 groups of brain tumor patients. The investigation involved 27 adult tumor subjects, 25 of whom had undergone resection and radiotherapy. Ten normal adults acted as controls. The 4 tumor groups were based on neuroanatomic locus - focal lesions were localized to clearly defined visuospatial areas in the left or right posterior parietal cortex or prefrontal cortex. Neuroanatomic and visuospatial assessment parameters were specified: only allocentric ('mental' or 'conceptual') operations were examined. A theoretical framework outlined the role of the posterior parietal and prefrontal cortices in allocentric spatial processing. Six visuospatial tests involving allocentric operations were applied to patients in whom tumors involved these cortical areas. In numerous analyses, the 4 tumor groups showed no significant differences with the control group on the allocentric tests. Between-group comparisons were also not significant. Analyses by gender revealed significant differences on shape rotation and line orientation tests, especially in the right hemisphere and parietal groups. Comparisons between focal radiation subgroups and 'nonradiation' subgroups produced unclear results. The main conclusions are that despite the presence of frontal or parietal tumors, (1) allocentric processing is hardly compromised, and (2) females show lower spatial performance than males due to tumor-related effects on a pre-existing pattern of cerebral lateralization. The study emphasizes the need to address visuospatial function in the neuropsychological study of brain tumor patients, particularly the role of intact spatial processing in this patient group. PMID- 11212904 TI - Intracranial low-grade chondrosarcoma with hyperostosis of the skull: a case report. AB - We describe a case of intracranial chondrosarcoma in a 46-year-old woman. The preoperative diagnosis was meningioma as plain radiography and computed tomography of the head revealed a tumor with discrete calcifications predominantly in the right frontoparietal region and hyperostosis of the inner table of the skull overlying the tumor. However, the tumor was histologically composed of cartilaginous tissue without meningiomatous differentiation and the final diagnosis was a low-grade chondrosarcoma based on its histological appearance and size, together with the radiologic images. Intracranial chondrosarcoma occurring above the skull base is extremely rare and 19 cases were found in our literature review. Intracranial chondrosarcoma showing hyperostosis of the skull has not been reported in the cases. The discussion includes its differential diagnosis, origin, and clinical behavior. PMID- 11212905 TI - A randomized phase II and pharmacokinetic study of dacarbazine in patients with recurrent glioma. AB - We conducted a randomized phase II study to determine the efficacy of dacarbazine (DTIC) in recurrent gliomas. Patients were randomly assigned to receive either DTIC 750 mg/m2 IV day 1 every 28 days (Arm A) or DTIC 200 mg/m2 IV days 1-5 every 28 days (Arm B). Pharmacokinetics were studied in 6 patients on each arm using HPLC analysis. Thirty-nine patients (30 male, 9 female), ages 27-67 years (median 53) were entered on the study (20 on Arm A, 19 on Arm B). No objective responses were seen. Median time to progression was 3 months. Median survival was 8 months. Treatment was generally well tolerated. Major toxicities were grade 1-2 nausea (33%). lethargy (28%), diarrhea (15%), alopecia (15%), and grade 3 neutropenia (8%). Four patients on Arm A had mild self-limited episodes of intravascular hemolysis occurring immediately after drug infusion, the mechanism of which is unknown. Mean AUC for DTIC, HMMTIC (5-[3-hydroxymethyl-3-methyl-1-triazeno] imidazole-4-carboxamide), and MTIC (5-[3-methyl-1-triazenol imidazole-4 carboxamide), in Arm A were 14.8, 0.17, and 1.15 mM min, respectively. Corresponding values for Arm B (on day 1 of 5) were 1.7, 0.06, and 0.29 mM min, respectively. The predicted HMMTIC and MTIC exposure over 5 days for Arm B, based on the day 1 data, is higher than with Arm A. We conclude that DTIC is well tolerated but does not have activity in patients with recurrent gliomas. The 5 day schedule appears less toxic, and pharmacokinetic studies show that it provides greater exposure to MTIC and HMMTIC compared to the one-day schedule. PMID- 11212906 TI - Evidence of therapeutic efficacy of CCNU in recurrent choroid plexus papilloma. AB - A pregnant 33-year old woman developed nystagmus and cerebellar ataxia. A tumor in the roof of the fourth ventricle was diagnosed. The tumor was subtotally removed using microneurosurgical techniques. The histopathological diagnosis was choroid plexus papilloma (CPP). Twenty-one months later, the tumor recurred and was reoperated. Histologically the tumor displayed now increased mitotic activity and pleomorphism. Radiation therapy of the neuroaxis was performed. Within 59 months, the CPP recurred 3 more times with neuroradiological evidence of extensive spinal seeding. After several palliative irradiations, including 2 gamma-knife boosts, the patient was referred to chemotherapy. She was treated with CCNU (Lomustin) 100 mg/m2 orally (12 cycles, cumulative dosis 1440 mg/m2). Within 42 months, there was no new local recurrence and spinal seeding showed significant regression. Clinically the patient improved and stabilized, but needs continuous support because of persisting severe gait ataxia. The course of disease in our patient provides evidence for therapeutic efficacy of CCNU in recurrent CPP. PMID- 11212907 TI - Functional complementation between mutations at two distant positions in Escherichia coli RNA polymerase as revealed by second-site suppression. AB - Subunit-subunit interactions are critical for the assembly of the core of Escherichia coli RNA polymerase. The mutant alpha-subunit C131A is unable to complement the temperature-sensitive alpha-R45C mutant strain, which is defective for binding of the beta-subunit. In vitro reconstitution experiments, however, indicate that the alpha-C131A variant is able to form the intermediate alpha2beta, but is defective in contacting the beta'-subunit. We used this alpha C131A mutant to isolate a suppressor mutation in the beta'-subunit. Genetic and biochemical characterization of the beta' suppressor indicates the allele specific nature of its effect. Sequence analysis of the suppressor revealed a single substitution of Gly at position 333, an evolutionarily conserved position in the conserved region C of the beta'-subunit, by Asp. However, the crystal structure of the bacterial RNA polymerase indicates that the primary mutation (alpha-C131A) and its suppressor lie far apart. Thus, we propose that long-range interactions, as in this case, may play an important role in the functional assembly of E. coli RNA polymerase. PMID- 11212908 TI - The complete DNA sequence of the mitochondrial genome of Physarum polycephalum. AB - The complete sequence of the mitochondrial DNA (mtDNA) of the true slime mold Physarun polycephalum has been determined. The mtDNA is a circular 62,862-bp molecule with an A+T content of 74.1%. A search with the program BLAST X identified the protein-coding regions. The mitochondrial genome of P. polycephalum was predicted to contain genes coding for 12 known proteins [for three cytochrome c oxidase subunits, apocytochrome b, two F1Fo-ATPase subunits, five NADH dehydrogenase (nad) subunits, and one ribosomal protein], two rRNA genes, and five tRNA genes. However, the predicted ORFs are not all in the same frame, because mitochondrial RNA in P. polycephalum undergoes RNA editing to produce functional RNAs. The nucleotide sequence of an nad7 cDNA showed that 51 nucleotides were inserted at 46 sites in the mRNA. No guide RNA-like sequences were observed in the mtDNA of P. polycephalum. Comparison with reported Physarum mtDNA sequences suggested that sites of RNA editing vary among strains. In the Physarum mtDNA, 20 ORFs of over 300 nucleotides were found and ORFs 14 19 are transcribed. PMID- 11212910 TI - The Rhizobium leguminosarum glnB gene is down-regulated during symbiosis. AB - Symbiotic nitrogen fixation involves the development, on the legume plant root, of specialised organs called nodules, within which plant photosynthates are exchanged for combined nitrogen of bacterial origin. The glnB gene encodes a signal transduction protein (P(II)) which is a component of the bacterial nitrogen regulation (Ntr) system and an essential regulator of ammonium assimilation. We demonstrate that in Rhizobium leguminosarum the glnB promoter is strongly regulated by nitrogen and NtrC, but still shows a significant level of activity in conditions of nitrogen excess. Expression of genes involved in nitrogen assimilation has been shown to be absent in nitrogen-fixing bacteroids, and, in agreement with this, we find that the glnB promoter is down-regulated during bacteroid differentiation at a time coincident with the arrest of bacterial division in the nodule. This pattern is common to other bacterial genes involved in nitrogen assimilation and it is noteworthy that the zone where the glnB promoter is active is coincident with the region in which NtrC is expressed. PMID- 11212909 TI - The Aspergillus nidulans bncA1 mutation causes defects in the cell division cycle, nuclear movement and developmental morphogenesis. AB - Wild-type Aspergillus nidulans conidia are uninucleate. The mutation bncA1 (binucleated conidia) was first described as a single mutation located on chromosome IV that caused formation of approximately 25% binucleate and 1% trinucleate conidia. In this study, we show that bncA1 conidia exit G1 arrest earlier than the wild type. Germlings have hyphal elements with abnormal morphology, elevated numbers of randomly distributed nuclei and an irregular septation pattern. Older hyphal elements undergo mitotic catastrophe, suggesting the nuclear division cycle of internal (nonterminal) elements is not arrested. The bncA1 mutation also causes aberrant morphogenesis of the asexual reproductive structure, the conidiophore. Metulae and phialides are elongated and have incorrect numbers of nuclei. Phialides also have internal septation that appears to delineate hyphal-like elements. Heterokaryon analysis using strains with contrasting auxotrophic markers showed that the bncA1 mutation resulted in a higher frequency of diploid and multinucleated prototrophic conidia than control heterokaryons. These results suggest that in bncA1 strains multiple nuclei can move from the conidiophore vesicle to the metulae and/or from the phialide to the conidium. The bncA1 mutant also showed hypersensitivity to the anti-microtubule drugs thiabendazole and nocodazole, which is consistent with the defects in cell cycle regulation and nuclear movement. We propose that bncA has an important role in correctly regulating both the cell division cycle and nuclear movement. PMID- 11212911 TI - Comparative analyses of the distribution of various transposable elements in Pyricularia and their activity during and after the sexual cycle. AB - We examined the distribution and activity of six transposable elements found in the blast fungus, Pyricularia spp. Sixty-eight isolates from various gramineous plants were used for the survey, and the elements were plotted on a dendrogram constructed on the basis of their rDNA-ITS2 sequences. MGR586 and Pot2 (Class II elements), Mg-SINE (SINE-like element) and MGR583 (LINE-like retrotransposon) were widely distributed among the Pyricularia isolates, suggesting that they are old elements which arose in, or invaded, the Pyricularia population at very early stages in its evolution. By contrast, the distribution of the LTR retrotransposons MAGGY and Grasshopper was limited or sporadic, suggesting that they are relatively new elements which recently invaded the Pyricularia population by means of horizontal transfer events. The activity of these elements was evaluated by Southern analysis in progenies derived from a cross between a Setaria isolate and a Triticum isolate. Many new MAGGY signals were observed, which were absent in the parental isolates, at various stages of the sexual cycle and following vegetative growth. In contrast, the other elements yielded few, if any, such signals. Analysis of the sequences flanking the new MAGGY insertions revealed that they were each associated with a 5-bp target-site duplication at both ends of the insertion. These data suggested that MAGGY was the most active of the elements tested for transposition in Pyricularia. PMID- 11212912 TI - A study of protein-protein interactions in living cells using luminescence resonance energy transfer (LRET) from Renilla luciferase to Aequorea GFP. AB - We have previously reported that Escherichia coli and mammalian cells containing a fusion protein consisting of the Renilla luciferase linked to Aequorea GFP exhibited luminescence resonance energy transfer (LRET) from luciferase to GFP in the presence of coelenterazine. In this paper, we describe the construction of two gene fusions in which the cDNA for insulin-like growth factor II (IGF-II) is connected to the cDNA for a "humanized" GFP, and the cDNA for insulin-like growth factor binding protein 6 (IGFBP-6) is linked to a cDNA encoding the Renilla luciferase (RUC). The expression of the fusion gene constructs in CHO cells resulted in single polypeptides with the molecular weights expected for IGF-II GFP and IGFBP-6-RUC, respectively, based on the use of antibodies against GFP and Renilla luciferase. The secretion of IGF-II-GFP from CHO cells was verified by fluorescence microscopy and the presence of IGFBP-6-RUC in the culture medium was confirmed by luminometry. The interaction between the two known binding partners, IGF-II and IGFBP-6, was monitored by measuring LRET from the IGFBP-6-RUC protein to IGF-II-GFP in the presence of coelenterazine, using a low-light imaging system and spectrofluorometry. Based on these data, luciferase-to-GFP LRET holds great promise for the study of protein-protein interactions in eukaryotic cells in real time. PMID- 11212913 TI - The endogenous Drosophila melanogaster retrovirus gypsy can propagate in Drosophila hydei cells. AB - The endogenous Drosophila melanogaster retrovirus gypsy (mdg4) forms virus-like particles (VLPs) which are found as extracellular particles in the medium used to culture D. melanogaster cells. The D. hydei somatic cell line DH14, which does not harbour gypsy sequences, was exposed to D. melanogaster VLPs. Subsequent PCR and Southern analysis revealed that gypsy elements had penetrated into the D. hydei cells, suggesting interspecific transmission of the retrovirus. A D. hydei cell line containing gypsy sequences was established and grown in a mixed culture together with the G418-resistant D. hydei cell line DH33, and gypsy was shown to be transmitted from cell to cell. The proportion of cells carrying gypsy increased with time. The rate of gypsy invasion of the lines DH14 and DH33 was 10(-3) and 10(-2) per cell per generation, respectively. The results demonstrate the possibility of interspecific horizontal transfer of gypsy in the form of its VLPs. PMID- 11212914 TI - Variation in sequence and RNA editing within core domains of mitochondrial group II introns among plants. AB - The 3' regions of several group II introns within the mitochondrial genes nad1 and nad7 show unexpected sequence divergence among flowering plants, and the core domains 5 and 6 are predicted to have weaker helical structure than those in self splicing group II introns. To assess whether RNA editing improves helical stability by the conversion of A-C mispairs to A-U pairs, we sequenced RT-PCR amplification products derived from excised intron RNAs or partially spliced precursors. Only in some cases was editing observed to strengthen the predicted helices. Moreover, the editing status within nad1 intron 1 and nad7 intron 4 was seen to differ among plant species, so that homologous intron sequences shared lower similarity at the RNA level than at the DNA level. Plant-specific variation was also seen in the length of the linker joining domains 5 and 6 of nad7 intron 3; it ranged from 4 nt in wheat to 11 nt in soybean, in contrast to the 2-4 nt length typical of classical group II introns. However, this intron is excised as a lariat structure with a domain 6 branchpoint adenosine. Our observations suggest that the core structures and sequences of these plant mitochondrial introns are subject to less stringent evolutionary constraints than conventional group II introns. PMID- 11212915 TI - Molecular control of copper homeostasis in filamentous fungi: increased expression of a metallothionein gene during aging of Podospora anserina. AB - The lifespan of the ascomycete Podospora anserina was previously demonstrated to be significantly increased in a copper-uptake mutant, suggesting that copper is a potential stressor involved in degenerative processes. In order to determine whether changes in copper stress occur in the cells during normal aging of cultures, we cloned and characterized a gene coding for a component of the molecular machinery involved in the control of copper homeostasis. This gene, PaMt1, is a single-copy gene that encodes a metallothionein of 26 amino acids. The coding sequence of PaMt1 is interrupted by a single intron. The deduced amino acid sequence shows a high degree of sequence identity to metallothioneins of the filamentous ascomycete Neurospora crassa and the basidiomycete Agaricus bisporus, and to the N-terminal portion of mammalian metallothioneins. Levels of PaMt1 transcript increase in response to elevated amounts of copper in the growth medium and during aging of wild-type cultures. In contrast, in the long-lived mutant grisea, transcript levels first increase but then decrease again. The ability of wild-type cultures to respond to exogenous copper stress via the induction of PaMt1 transcription is not affected as they grow older. PMID- 11212917 TI - RpoN of Rhizobium leguminosarum bv. viciae strain VF39SM plays a central role in FnrN-dependent microaerobic regulation of genes involved in nitrogen fixation. AB - The rpoN gene, which codes for the alternative transcription factor sigma54, was cloned and sequenced from Rhizobium leguminosarum strain VF39SM. Construction of a rpoN mutant allowed analysis of the role of RpoN as a transcriptional regulator of genes carrying lacZ reporter fusions. Analysis of a rpoN::lacZ transcriptional fusion in the rpoN background revealed that this gene was negatively autoregulated. Site-directed mutagenesis was used to demonstrate that this autoregulation was dependent on a reverse complement RpoN binding site located upstream of the rpoN gene. rpoN was shown to be required for full microaerobic expression of both copies of fixGHIS, as well as of fixNOQP, despite the absence of apparent rpoN binding sites upstream of fixG. Moreover, rpoN was found to be required for full microaerobic expression of fnrN, which in turn is absolutely required for microaerobic induction of fixGHIS. This suggests that the reduced fixG::lacZ expression seen in the rpoN background is due to the dependence of fnrN expression on RpoN. PMID- 11212916 TI - Transcriptional regulation of the Saccharomyces cerevisiae amino acid permease gene BAP2. AB - Uptake of branched-chain amino acids by Saccharomyces cerevisiae from media containing a preferred nitrogen source is mediated by the permeases encoded by BAP2, BAP3, and VAP1/TAT1. The transcriptional activity of the BAP2 promoter is affected by a number of genes, including SSY1, which encodes an amino acid permease homologue that is necessary for transcription of BAP2. Other genes that control BAP2 encode known (Leu3p, Tup1p) and putative (Stp1p, Stp2p) transcription factors. We present evidence that the zinc-finger proteins Stp1p and Stp2p bind directly to the BAP2 promoter. Binding of Stplp to the BAP2 promoter in vivo and in vitro indicates that the STP gene family indeed encodes transcription factors. The presence of a Leu3p binding site in the BAP2 promoter is required for full promoter activity on synthetic complete medium. The capacity of Leu3p to activate BAP2 transcription correlates with conditions that affect the level of alpha-isopropyl malate. The effect of a tup1 deletion on BAP2 transcription depends on SSY1. In an ssy1 strain, the phenotype of tup1 conforms to the well-established role of Tup1p as part of a repressor complex, but in the SSY1 strain deletion of TUP1 causes a decrease in transcription, indicating that Tup1p may also have an activating role at the BAP2 promoter. Our results thus suggest a complex interplay between several transcription factors in the expression of BAP2. PMID- 11212918 TI - Integrated structures of the linear plasmid SCP1 in two bidirectional donor strains of Streptomyces coelicolor A3(2). AB - The linear plasmid SCP1 is integrated into the central region of the chromosome of Streptomyces coelicolor A3(2). The integrated structures of SCP1 in two bidirectional donor strains, 2612 and A634, were analyzed by cloning and sequencing of the junctions between the SCP1 DNA and the chromosomal DNA. In the NF (normal fertility) strain 2612, SCP1 is integrated in a right-handed direction into ORF-X at the left end of the IS cluster in AseI fragment E. An almost intact left end of SCP1 is retained, while the right terminal inverted repeat (TIR-R) of SCP1 and a 33-kb chromosomal DNA segment including the IS cluster are deleted. In the NF-like strain A634, SCPI is also integrated into AseI fragment E in a left handed direction. The left junction is composed of IS466 with complete deletion of TIR-R of SCP1, and the right junction is located at the left end of IS468A* with half of TIR-L being deleted. During the integration event, a 5.4-kb chromosomal DNA segment including IS468A, IS468B, IS469 and IS466A was duplicated so that this sequence is now present on both sides of SCP1. Since 2612 and A634 exhibit a similar bidirectional gradient of gene transfer, it is surprising that their chromosomal structures are so different. PMID- 11212919 TI - Multiple isoforms of the Drosophila Spatzle protein are encoded by alternatively spliced maternal mRNAs in the precellular blastoderm embryo. AB - The spatzle gene is required for proper specification of positional information along the dorsal-ventral axis of the Drosophila embryo and for induction of the innate immune response to fungal infection. It has been shown to encode a precursor of a Nerve Growth Factor-like ligand which is also a member of the cysknot protein superfamily. In dorsal-ventral patterning, the most widely accepted model of the pathway places Spatzle at the end of a ventrally restricted protease cascade that results in the proteolytic processing of the precursor form of Spatzle to an active ligand which is thought to bind to the Toll receptor. Here we show that the spatzle gene encodes at least ten different protein isoforms as a result of complex alternative splicing in precellular blastoderm embryos. Multiple transcripts are clearly present up until the time of cellularization, at which point most transcripts can no longer be detected. Nine isoforms were expressed and at least five are efficiently secreted in a heterologous protein expression system. RNA microinjection experiments demonstrate that three isoforms completely rescue embryos from spatzle null mothers, while most of the others rescue to a lesser extent. The phenotypic rescue activities of several isoforms and the relevance of these isoforms to the generation of the ventralizing signal are discussed. PMID- 11212920 TI - Transposition of the maize transposable element Ac in barley (Hordeum vulgare L.). AB - Transposition of the maize autonomous element Ac (Activator) was investigated in barley (Hordeum vulgare L.) with the aim of developing a transposon tagging system for the latter. The Ac element was introduced into meristematic tissue of barley by microprojectile bombardment. Transposon activity was then examined in the resulting transgenic plants. Multiple excision events were detected in leaf tissue of all plant lines. The mobile elements generated empty donor sites with small DNA sequence alterations, similar to those found in maize. Reintegration of Ac at independent genomic loci in somatic tissue was demonstrated by isolation of new element-flanking regions by AIMS-PCR (amplification of insertion-mutagenized sites). In addition, transmission of transposed Ac elements to progeny plants was confirmed. The results indicate that the introduced Ac element is able to transpose in barley. This is a first step towards the establishment of a transposon tagging system in this economically important crop. PMID- 11212921 TI - Molecular characterization of co-transcribed genes from Streptomyces tendae Tu901 involved in the biosynthesis of the peptidyl moiety and assembly of the peptidyl nucleoside antibiotic nikkomycin. AB - Six genes (nikP1, nikP2, nikS, nikT, nikU, and nikV) from Streptomyces tendae Tu901 were identified by analysis of the nucleotide sequence of the nikkomycin gene cluster. These genes, together with the previously described nikQ and nikR, span 9.39 kb and are transcribed as a polycistronic mRNA in a growth-phase dependent manner. The nikP1 gene encodes a non-ribosomal peptide synthase consisting of an adenylation domain, a thiolation domain, and an N-terminal 70 residue segment of unknown function. The amino acid sequence encoded by the nikP2 gene displays similarity to the sequences of thioesterases, and the nikS product belongs to a superfamily of proteins characterized by a specific ATP-binding fold. The N-terminal 70 amino acids of the predicted nikT gene product show significant sequence similarity to acyl carrier proteins, and the C-terminal 330 amino acids to aminotransferases. The sequences of the deduced proteins NikU and NikV exhibit similarity to components S and E, respectively, of glutamate mutase from Clostridium. Disruption of the nikP1, nikS, nikT, or nikV gene by insertion of a kanamycin resistance cassette abolished formation of nikkomycins I, J, X, and Z, all of which contain hydroxypyridylhomothreonine as the peptidyl moiety. The nikP1 mutants, and the nikS and nikT mutants accumulated the nucleoside moieties nikkomycin Cz, and nikkomycins Cx and Cz, respectively. The nikV mutants formed nikkomycins Ox and Oz, which contain 2-amino-4-hydroxy-4-(3'-hydroxy-6' pyridyl) butanoic acid as the peptidyl moiety. The nikP2 mutants synthesized nikkomycins I, J, X, and Z, but amounts of nikkomycins I and X, which contain formylimidazolone as the base, were lower. Feeding formylimidazolone to nikP2 mutants restored the ability to form nikkomycins I and X. Our results indicate that nikU and nikV are required for the synthesis of hydroxypyridylhomothreonine, the genes nikP1, nikP2 and nikS are required for the assembly of nikkomycins, and nikT is required for both pathways. The putative activities of each of their products are discussed. PMID- 11212922 TI - Two novel genes encoding SNF-1 related protein kinases from Arabidopsis thaliana: differential accumulation of AtSR1 and AtSR2 transcripts in response to cytokinins and sugars, and phosphorylation of sucrose synthase by AtSR2. AB - We searched for genes encoding members of the group-3 SNF1-related protein kinase (SnRK3) family in the Arabidopsis thaliana database, and seven independent sequences were identified. Transcripts of two of them were found to accumulate differentially upon treatment with light, cytokinins and sugars. Full-length cDNAs were isolated and designated as AtSR1 and AtSR2; they encode polypeptides of 442 and 429 amino acids with relative molecular masses of 50.3 kDa and 48.2 kDa, respectively. In etiolated seedlings, no transcripts of either gene were observed. However, upon exposure to light or cytokinins, transcripts of AtSR1 but not AtSR2 began to accumulate. The induction with light was greatly reduced in the presence of a cytokinin antagonist, suggesting that cytokinins are involved in light-signaling pathways. In contrast, transcription of AtSR2, but not of AtSR1, was greatly increased by sucrose, as well as glucose and fructose. AtSR2 expressed in E. coli efficiently phosphorylated sucrose synthase in the presence of manganese ions. These results suggest that, although SnRK3 proteins may generally be involved in sugar metabolism, expression of AtSR1 and AtSR2 is differentially and distinctly regulated by various external signals, and AtSR2 may function in the regulation of sucrose synthase by specific phosphorylation. PMID- 11212923 TI - Comparison of psbK operon organization and group III intron content in chloroplast genomes of 12 Euglenoid species. AB - A novel mixed operon has been identified in the photosynthetic protist E. gracilis. The genes for psbK, ycf12, psaM, and trnR are co-transcribed. The resulting tetracistronic transcripts are processed through endonucleolytic cleavage of the intergenic spacers and intron splicing to form three mature monocistronic mRNAs and a tRNA. A group III twintron and a group III intron are located in psbK. Another group III intron is found in ycf12. The psbK operon has been cloned by PCR amplification from nine related Euglenoid species. In each species, the gene order and content of the psbK operon is conserved. The psbK operons contain phylogenetically conserved eubacterial promoter, translational, and 3' processing elements. Intron content varies significantly from species to species. Based on a comparison of the intron content with the results of phylogenetic analysis, group III intron evolution within the Euglenoid lineage is much more complex than previously believed. PMID- 11212924 TI - DNA circle formation in Neisseria gonorrhoeae: a possible intermediate in diverse genomic recombination processes. AB - An important attribute that contributes to the virulence of Neisseria gonorrhoeae is its phenotypic variability, which is based on recombination within complex gene families in the genome. In this study we report on the in vivo amplification of large segments of the genome and the existence of circular DNA intermediates in the cell, which might help to explain the evolution of these gene families and provide possible clues as to how genetic variability is maintained. Using an inserted chromosomal marker (cat) in the N. gonorrhoeae MS11 genome that confers low-level resistance to chloramphenicol (Cm), we isolated variants that express resistance to high levels of Cm. Genetic analysis revealed that virtually all variants harboured single or multiple tandem amplifications of the respective genome segments carrying the cat insert. This process occurred independently of both the location of the cat insertion site and of the presence of a functional recA gene. Analysis of the genetically well characterised pilC region revealed a head-to-tail orientation of the amplified segments, with the junctions being located within direct repeats. Identical junctions were detected in extra chromosomal circular DNA molecules isolated from non-selected wild-type and recA strains, suggesting that both types of structure arise by related processes. The existence of DNA circles was shown by their banding behaviour in caesium chloride/ethidium bromide density centrifugation and their resistance to digestion by exonuclease. The possible roles of such circles in processes such as pilin gene recombination, chromosomal gene amplification and genetic transformation are discussed. PMID- 11212925 TI - Involvement of SGS1 in DNA damage-induced heteroallelic recombination that requires RAD52 in Saccharomyces cerevisiae. AB - The SGS1 gene of Saccharomyces cerevisiae is homologous to the genes that are mutated in Bloom's syndrome and Werner's syndrome in humans. Disruption of SGS1 results in high sensitivity to methyl methanesulfonate (MMS), poor sporulation, and a hyper-recombination phenotype including recombination between heteroalleles. In this study, we found that SGS1 forms part of the RAD52 epistasis group when cells are exposed to MMS. Exposure to DNA-damaging agents causes a striking, Rad52-dependent, increase in heteroallelic recombination in wild-type cells, but not in sgs1 disruptants. However, in the absence of DNA damage, the frequency of heteroallelic recombination in sgs1 disruptants was several-fold higher than in wild-type cells, as described previously. These results imply a function for Sgs1: it acts to suppress spontaneous heteroallelic recombination, and to promote DNA damage-induced heteroallelic recombination. PMID- 11212926 TI - An Aspergillus nidulans uvsC null mutant is deficient in homologous DNA integration. AB - The Aspergillus nidulans uvsC gene was identified as a homolog of RAD51 and recA of Saccharomyces cerevisiae and Escherichia coli, respectively, whose role in genetic recombination and recombinational repair has been extensively studied. Like many other filamentous fungi, A. nidulans shows no bias towards either homologous or ectopic integration of exogenous DNA. Therefore it is a unique and useful organism for the study of the mechanisms of DNA integration. Homologous integration of a 1.7-kb argB gene was not detected in 50 transformants obtained from a uvsC null mutant. In contrast, the frequency of homologous integration in uvsC+ control strains varied from 41 to 86%. Another feature observed with the uvsC null mutant was that an increased number of transformants had undergone ectopic integrations at multiple sites in the genome. These results are consistent with the established function of Rad51/RecA, and further indicate the involvement of redundant pathways in integration of exogenous DNA. This study provides direct evidence for the involvement of uvsC in exogenous DNA integration and should contribute to the improvement of genetic manipulations in general, but particularly in fungi. PMID- 11212927 TI - Growth and recombination of phage lambda in the presence of exonuclease V from Bacillus subtilis. AB - When expressed in Escherichia coli, the AddAB exonuclease/recombinase from Bacillus subtilis blocks the growth of phage lambda. Mutants of lambda that are deleted for ea47, a gene of unknown function which is expressed early in the lytic cycle, are not blocked for growth. The blocked-growth phenotype of lambda ea47+ in the presence of AddAB is expressed only when phage DNA replication is permitted. PMID- 11212928 TI - Transposition of autonomous and engineered impala transposons in Fusarium oxysporum and a related species. AB - The impala transposon of Fusarium oxysporum is an active element. We demonstrated that the imp160 copy, transposed into the gene encoding nitrate reductase, is an autonomous element, since it excises from this gene and reinserts at a new genomic position in backgrounds free of active elements. An element in which the transposase gene was replaced by a hygromycin B resistance gene was used (1) to demonstrate the absence of endogenous transposase in several F. oxysporum strains and (2) to check the ability of different genomic copies of impala to transactivate this defective element. This two-component system allowed the identification of autonomous elements in two impala subfamilies and revealed that transactivation can occur between highly divergent elements. We also demonstrate that the autonomous copy transposes in a closely related species complex, F. moniliforme, in a fashion similar to that observed in F. oxysporium. The ability of impala to function as a two-component system and to transpose in a heterologous host promises further advances in our understanding of the factors that modulate transposition efficiency and demonstrates the potential of impala as a means of establishing a transposon tagging system for a wide range of fungal species. PMID- 11212929 TI - A brief historical review of research achievements by the OVI during the 20th century against the background of socioeconomic and political developments in South Africa. PMID- 11212930 TI - Bone, blood and faecal response to an acidogenic lick for range cattle using different concentrations of ammonium chloride. AB - Thirty Brahman-Angus cross heifers at breeding age on extensive grazing were used to test the effectiveness of NH4Cl as an acidogenic agent at 15,18, 21 and 26 % of a dicalcium phosphate lick (A+), compared to a lick of 5 parts dicalcium phosphate and 3 parts salt (A-). Blood and faecal phosphorus (P), faecal calcium (Ca) and faecal magnesium (Mg) were significantly (P<0.05) higher in A+ compared to A-animals at different stages of the experiment. Bone P did not increase in response to NH4Cl but bone Ca was significantly (P<0.05) higher in A+ animals offered 18% NH4Cl and significantly (P<0.05) lower at 15 and 26%. Bone Mg in A+ animals was significantly (P<0.05) higher at 15 and 18% NH4Cl and lower at 26% NH4Cl compared to A- animals. Percentage ash in bone increased linearly from 62.5 to 64.9% in A+ animals as NH4Cl was increased in the lick from 15 to 21% and then decreased to 63.3% but was significantly (P<0.05) greater than the percentage ash in A-animals when the NH4Cl was increased to 26%. Bone mineral status was only marginally improved by adding NH4Cl to the lick in this study but blood P was significantly (P<0.05) improved in A+ compared to A- animals when the lick contained 15, 21 and 26% NH4Cl. Based on bone mineral results reported here, it is recommended that, when NH4Cl is used as an acidogenic agent in licks for range cattle, the amount in the lick should not exceed 21%. PMID- 11212931 TI - Control of immature stages of the flea Ctenocephalides felis (Bouche) in carpets exposed to cats treated with imidacloprid. AB - Fleas cause allergic dermatitis in cats and dogs and therefore warrant control. It has been demonstrated previously that there is marked inhibition of the development of the immature stages of the cat flea Ctenocephalides felis on fleece blankets exposed to cats treated with imidacloprid. This study reports on the efficacy of imidacloprid in suppressing adult flea emergence in carpet exposed to treated cats. Circular discs of carpet pre-seeded with flea eggs and larvae were exposed to 6 untreated control and 6 topically treated (imidacloprid 10% m/v) cats 1 to 2 days after treatment and subsequently fortnightly for 6 weeks. Exposure times on alternate days were either 1 or 6 hours. Adult flea yield from carpets was determined 35 days after exposure. Differences between flea yield on control carpets and those exposed for 1 hour were significant only for days +1 and +14. For the 6-hour exposure, differences were significant at all times except on Day +43. The ability of imidacloprid to suppress the yield of adult fleas on carpets (6-hour exposure) steadily declined from 82 % (Day +2) to 12% (Day +43). For the 1-hour exposure it varied inconsistently between 0 and 83% over the 6-week study period. PMID- 11212932 TI - A survey of feline babesiosis in South Africa. AB - South Africa appears to be the only country where feline babesiosis is a significant clinical entity in domestic cats. Little is known about its epidemiology or the clinical challenges facing practitioners. A questionnaire posted to 1760 South African veterinarians was returned by 16%, representing approximately 40% of practices. Just over half reported seeing feline babesiosis, with most cases occurring in the coastal areas of the Western Cape, Eastern Cape and KwaZulu-Natal Provinces. Overall incidence is highest in summer, but seasonality is less pronounced in non-seasonal and winter rainfall areas. No age, breed or sex predisposition was identified. Weight loss, weakness, anaemia, fever and icterus are common clinical findings. Complications include hepatopathy, renal failure, pulmonary oedema, cerebral signs, immune-mediated haemolytic anaemia and concurrent infections. The antibabesial drug of choice is primaquine phosphate. Response to therapy is generally good, but recurrence and chronic infections were identified as problems. The average mortality rate was 15%. Approximately 3000 cases are seen annually by the respondents, at an estimated cost of R750 000 to the owners. Feline babesiosis is a significant problem in South Africa, and further investigations of taxonomic status, concurrent infections, chemotherapy, complications and management of refractory cases are warranted. PMID- 11212933 TI - Effects of xylazine on acid-base balance and arterial blood-gas tensions in goats under different environmental temperature and humidity conditions. AB - The effects of acute exposure to 3 different temperature and humidity conditions on arterial blood-gas and acid-base balance in goats were investigated after intravenous bolus administration of xylazine at a dose of 0.1 mg/kg. Significant (P<0.05) changes in the variables occurred under all 3 environmental conditions. Decreases in pH, partial pressure of oxygen and oxyhaemoglobin saturation were observed, and the minimum values for oxygen tension and oxyhaemoglobin saturation were observed within 5 min of xylazine administration. The pH decreased to its minimum values between 5 and 15 min. Thereafter, the variables started to return towards baseline, but did not reach baseline values at the end of the 60 min observation period. Increases in the partial pressure of carbon dioxide, total carbon dioxide content, bicarbonate ion concentration, and the actual base excess were observed. The maximum increase in the carbon dioxide tension occurred within 5 min of xylazine administration. The increase in the actual base excess only became significant after 30 min in all 3 environments, and maximal increases were observed at 60 min. There were no significant differences between the variables in the 3 different environments. It was concluded that intravenous xylazine administration in goats resulted in significant changes in arterial blood-gas and acid-base balance that were associated with hypoxaemia and respiratory acidosis, followed by metabolic alkalosis that continued for the duration of the observation period. Acute exposure to different environmental temperature and humidity conditions after xylazine administration did not influence the changes in arterial blood-gas and acid-base balance. PMID- 11212934 TI - Acute pancreatitis: a newly recognised potential complication of canine babesiosis. AB - This retrospective study describes 4 cases of canine babesiosis with histologically confirmed acute pancreatitis. In addition, 16 dogs with babesiosis are reported with serum amylase (>3500 U/l) and/or lipase (>650 U/l) activity elevations of a magnitude that would support a diagnosis of probable acute pancreatitis, although extra-pancreatic sources of the enzymes could not be excluded in these cases. Median time of pancreatitis diagnosis was 2.5 days post admission, with primarily young (median age 3 years), sexually intact dogs affected. The development of pancreatitis was unrelated to the degree of anaemia at time of admission. In addition to pancreatitis, 80% of cases suffered from other babesial complications, namely icterus (13), acute respiratory distress syndrome (6), immune-mediated haemolytic anaemia (6), renal failure (3), haemoconcentration (2) and cerebral syndrome (2). Acute respiratory distress syndrome, renal failure and cerebral syndrome were associated with a poor prognosis, with 4 of the 5 dogs included in the overall 26% mortality rate having at least 1 of these complications. Haemolytic anaemia with ischaemia-reperfusion injury to the pancreas is proposed as a possible primary pathophysiological mechanism in babesial pancreatitis. Hypotensive shock, immune-mediated haemolytic anaemia, haemoconcentration and possibly altered lipid metabolism in babesiosis may also be involved. The previously postulated pro-inflammatory cytokine milieu of complicated babesiosis may underlie the progression, if not the primary initiation, of pancreatic pathology. Acute pancreatitis may represent the previously reported 'gut' form of babesiosis. PMID- 11212935 TI - The use of herbal preparations for tick control in western Ethiopia. AB - Information on the traditional tick control methods used in Keffa, Illubabor and Wellega Provinces in western Ethiopia was obtained from 86 veterinary clinics and 865 peasant farmers through a questionnaire survey. Latexes of Euphorbia obovalifolia and Ficus brachypoda, juice of crushed leaves of Phytolaca dodecandra and Vernonia amygdalina, fruit juice of Solanum incanum, crushed seeds of Lepidium sativum mixed with fresh cattle faeces, juice of crushed leaves and bark of Calpurnea aurea and commercially available spice of Capsicum spp. mixed with butter, were used by peasant farmers to control ticks. Preliminary in vitro efficacy tests of these plant preparations were performed on engorged female Boophilus decoloratus. Preparations of Capsicum spp., E. obovalifolia, S. incanum and F. brachypoda were found to have 30-100% killing effects. Subsequently, in vivo treatment trials of these preparations were conducted using indigenous Bos indicus cattle naturally infested with ticks. Results indicate that treatments at the rate of once per day for 5 consecutive days with the latexes of E. obovalifolia and F. brachypoda can reduce tick burdens by up to 70% on cattle. PMID- 11212936 TI - Effect of dietary concentrate level on body immune response in calves fed a wheat straw-based diet. AB - Twenty 9-month-old crossbred calves were divided into 2 equal groups (A and B; n = 10). The feeding trial was conducted for 119 days to study the effect of concentrate supplementation on body immune response and blood metabolites in calves. The concentrate and roughage (wheat straw) ratio in the diet of Groups A and B was 60:40 and 30:70, respectively. Daily dry matter intake was significantly (P<0.01) higher in Group A than in Group B, which also resulted in significantly higher (P<0.01) total body weight gain in the former group. Protein, albumin, globulin, total and differential leukocyte count in blood were similar in the 2 groups but blood glucose level was higher (P<0.05) in the calves of Group A. There was no difference in body immune response between the groups, which indicated that body immune response of animals is not significantly influenced by restricted concentrate feeding. PMID- 11212937 TI - Isoflurane anaesthesia in an African wild dog, Lycaon pictus. AB - Anaesthesia was required in a captive female African wild dog (Lycaon pictus) for surgical wound treatment. After it was immobilised with a medetomidine-ketamine combination, bradycardia, hypothermia, systolic hypertension and metabolic acidosis were observed. Surgical anaesthesia was maintained with a 1% end-tidal isoflurane concentration. A decrease in the arterial blood pressure, rectal temperature and pH occurred during maintenance of anaesthesia. PMID- 11212938 TI - Helminth parasites of indigenous chickens in Oodi, Kgatleng District, Botswana. AB - Thirteen adult indigenous chickens from Oodi, Kgatleng district, Botswana, were examined for helminth parasites. Two species of nematodes, Ascaridia galli and Heterakis gallinarum, and species of the cestode genus Raillietina, were recovered. A. galli and H. gallinarum were the most commonly seen parasites. The nematode A. galli occurred concurrently with Raillietina spp. PMID- 11212939 TI - Parasites of domestic pigeons (Columba livia domestica) in Sebele, Gaborone, Botswana. AB - The following parasites were found in apparently healthy pigeons kept in Sebele: a haemoprotozoan, Haemoproteus columbae (80%); endoparasite metazoan nematodes, Ascaridia columbae (30%) and Dispharynx spiralis (10%); a cestode, Raillietina sp. (80%) and coccidian oocysts (40%); 2 ectoparasites, namely the pigeon fly, Pseudolynchia canariensis (50%) and the louse, Columbicola columbae (30%). The pigeons also had highantibody titres, (1:256) to the protozoan parasite Toxoplasma gondii (100%). The latter infection in these domestic pigeons has public health implications. PMID- 11212940 TI - Gastric Ollulanus tricuspis infection identified in captive cheetahs (Acinonyx jubatus) with chronic vomiting. AB - Gastritis, vomition and weight loss are common in captive cheetahs (Acinonyx jubatus). Gastric spiral bacteria (Helicobacter spp.) and the very small, viviparous nematode Ollulanus tricuspis, a stomach worm of cats, are believed to be important causes. Three sibling cheetahs at Wellington Zoo, New Zealand, developed chronic vomiting, diarrhoea and debility. Their parents were both South African-born. Response to antibacterial treatment was poor. Endoscopic examinations revealed chronic lymphoplasmacytic gastritis and Ollulanus infection. Treatment with oxfendazole and pyrantel embonate resulted in clinical improvement; however, 1 cheetah, which died 7 months later as a result of a ruptured liver due to hepatic amyloidosis, still had Ollulanus worms present in her stomach. Ollulanus tricuspis is a significant cause of gastritis and vomiting in captive cheetahs, lions and tigers, as well as wild cougars and tigers. The parasite has not yet been found in sub-Saharan Africa. Because of the unusual characteristics of this parasite, the literature on its life history and techniques for diagnosis is reviewed. PMID- 11212941 TI - Vulvovaginectomy and neo-urethrostomy for treatment of haemangiosarcoma of the vulva and vagina. AB - Vulvovaginectomy and neo-urethrostomy were performed in a 9-year-old German shepherd dog following a diagnosis of infiltrative vulvar and vestibulovaginal haemangiosarcoma. The dog was presented for intermittent vulvar haemorrhage over a 3-month period. On examination the vulva and vestibulovagina were distended and firm. Vaginal discharge and fine needle aspiration cytology detected anaplastic cells. Haemangiosarcoma was diagnosed on biopsy. A new urethral opening was created in the floor of the vagina allowing resection of the vulva and caudal vestibulovagina. Urinary continence was preserved and healing was without complications. PMID- 11212942 TI - Molecular structure-based prediction of human abdominal skin permeability coefficients for several organic compounds. AB - Mechanistically based predictions of skin permeability coefficients (Kp) derived solely on the basis of molecular structure information of organic compounds have not been reported previously. The objective of the present study was to predict the human abdominal Kp of structurally unrelated organic compounds using a mechanistic equation that takes into account compound-specific and species specific determinants of Kp and relates the compound-specific determinants directly to molecular structure information. The method consisted of obtaining predictions based on a modified form of the conventional equation used to describe Kp (= P x D/L, where P, D, and L represent the stratum corneum:water partition coefficient, diffusion coefficient, and path length of diffusion). The value of P was predicted from the n-octanol:water partition coefficient (Po:w) computed from molecular structure information as well as the lipid, protein, and water contents in stratum corneum. The value of D was predicted according to the conventional Einstein-Stoke equation using the molar volume (Vmolar) of compounds computed from molecular structure information as well as data on viscosity of the stratum corneum components. Finally, the value of L was estimated in accordance with the characteristics of the diffusion pathways in the stratum corneum (i.e., transcellular and intercellular pathways). The average ratio of predicted Kp to the corresponding mean experimental values obtained from the literature was 1.25 (SD = 0.68, r = .95) for 47 structurally unrelated organic compounds (volatile organics and drugs), which were characterized by the presence of less than 2 hydrogen bonding groups and Vmolar < 231 cm3/mol. The present study is the first initiative that permits prediction of the human Kp of organic compounds by using molecular structure information as the sole chemical-specific input in a mechanistic equation. PMID- 11212943 TI - Correlation of blood cholinesterase levels with toxicity of sarin in rats. AB - The dose-mortality response curve for sarin when administered to pregnant rats is extremely steep. The pregnant animal either died during the treatment or survived with no observable fetal toxicity. Animals that died displayed many symptoms characteristic of anticholinesterase toxicity. The present study was conducted to determine whether the maternal deaths, clinical observations, and/or weight loss could be correlated with baseline blood cholinesterase levels in individual animals. Cholinesterase levels (plasma and erythrocyte) were obtained prior to, during, and following treatment of nonpregnant rats by gavage with 380 microg/kg/d sarin for 10 d. After the first dose, there was a drop in the plasma cholinesterase levels, which then remained low throughout the dosing period. There was a statistically significant correlation between body weight loss and plasma cholinesterase levels of the sarin dosed animals. The surviving animals also had lower plasma cholinesterase levels and lower body weights, both of which recovered on the cessation of dosing. The erythrocyte cholinesterase levels were not different between treated and nontreated rats. Neither plasma or erythrocyte baseline cholinesterase levels nor relative or absolute cholinesterase decline values could be used as predictors of mortality from sarin administration in rats. PMID- 11212944 TI - Quantitative modeling of suppression of IgG1, IgG2a, IL-2, and IL-4 responses to antigen in mice treated with exogenous corticosterone or restraint stress. AB - Exposure to toxic chemicals often induces a neuroendocrine stress response leading to increased concentrations of a variety of potentially immunomodulatory mediators. Corticosterone is a major stress-induced mediator that can be immunosuppressive. However, the quantity of corticosterone exposure required to produce particular decrements in particular immunological parameters is not known. Mice treated with various dosages of exogenous corticosterone were compared to mice exposed to a psychogenic stressor (restraint). Cumulative corticosterone exposure in these mice, expressed as the area under the curve (AUC) of corticosterone concentration versus time, was used to develop quantitative models of the effects of corticosterone on the immunoglobulin (Ig) G1 and IgG2a responses to keyhole limpet hemocyanin (KLH) and sheep erythrocytes (sRBC). The production of interleukin (IL)-2 and IL-4 by splenocytes stimulated with KLH in culture was also evaluated. Linear regression models were derived that describe the relationship between the IgG1 and IgG2a responses to KLH. Restraint had a greater effect (at equivalent corticosterone AUC values) than exogenous corticosterone, suggesting that mediators in addition to corticosterone are important in suppression of the IgG1 and IgG2a response to KLH. The production of IL-2 and IL-4 by cultured splenocytes was mostly, but not always, consistent with the changes in IgG1 or IgG2a. For example, the regression lines for IgG2a (a Th1-driven response) and IL-2 (a Th1 cytokine) were not significantly different. The relationships between corticosterone AUC and the IgG1 and IgG2a responses to sRBC were nonlinear and characterized by enhanced responses at low to moderate AUC values. The quantitative models developed here have implications for risk assessment in immunotoxicology. PMID- 11212945 TI - Effects of PCB 126 on thymocyte surface marker expression and immune organ development in chicken embryos. AB - Previous studies have shown that chicken (Gallus domesticus) embryos are sensitive to the immunotoxic effects of Ah receptor agonists. These chemicals cause atrophy of the thymus gland and bursa of Fabricius, the sites of T- and B lymphocyte maturation, respectively. The objectives of this study were (1) to evaluate the effects of 3,3,4,4',5-pentachlorobiphenyl (PCB 126) on thymocyte phenotypes (CD4-CD8-, CD4+CD8+, CD4+CD8-, CD4-CD8+, TCRalphabeta+, and TCRgammadelta) in chicken embryos, and (2) to compare phenotype alterations with masses and cellularity of lymphoid organs. To simulate exposure in wild avian embryos, chicken eggs were injected with PCB 126 (sunflower oil carrier) into the air cell before incubation. Doses ranged from 0.051 to 0.8 ng/g egg with carrier injected and noninjected control groups. The thymus and bursa were removed, weighed, and homogenized on d 20 of egg incubation (1 d before hatch). Thymocyte phenotypes were quantified by flow cytometry using monoclonal antibodies for CD4, CD8, TCRalphabeta (Vbeta1), and TCRgammadelta. Right thymus mass declined with dose, decreasing significantly between 0.32 and 0.8 ng/g to a size 28% lower than controls. Live lymphoid cell numbers in the right thymus dropped markedly (21% lower than controls) between 0.051 and 0.13 ng/g, with a further decrease (35% lower than controls) at higher doses. There was no significant change in the percentage of thymocytes expressing TCRalphabeta. The total number of TCRalphabeta+ thymocytes decreased with dose as a function of the declines in TCRalphabeta+ percentages and total thymocyte numbers. The percentages of all other measured phenotypes were unaltered by PCB 126. The total number of CD4+CD8+ cells, and to a lesser degree CD4-CD8+ cells, decreased in a dose-dependent manner following the pattern of total live thymocytes. The number of viable lymphoid cells in the bursa decreased to 45% lower than controls at 0.13 ng/g and fell to 76% lower than controls at 0.8 ng/g. Lymphoid atrophy occurred at doses that were 8- to 12-fold lower with full-term incubation as compared to exposure only during later stages of incubation, and the lymphoid atrophy was associated with decreased TCRalphabeta+ thymocytes at higher doses. These immunological effects were observed at concentrations of PCB 126 comparable to those found in Great Lakes herring gull eggs, after correcting for interspecies differences in sensitivity to PCB 126. PMID- 11212946 TI - Effects of sodium diethyldithiocarbamate on type II pulmonary epithelial cells in vitro. AB - Dithiocarbamates (DDTC) are chemicals widely used in the form of pesticides, therapeutic and chelating agents, and scavengers. Since DDTC interfere with SH, Cu, and Zn enzymes due to chelating properties, it was of interest to clarify, in primary culture of type II alveolar pneumocytes, the effect of this compound upon enzymes of glutathione cycle, Cu, Zn-superoxide dismutase, and the membrane structure of cells. DDTC significantly inhibited the activity of superoxide dismutase and the activity of gamma-glutamyl transpeptidase, glutathione reductase, and alkaline phosphatase, whereas an increase in the activity of glutathione peroxidase was found. The membranes of pneumocytes type II were injured. Data show that DDTC adversely affected type II pneumocyte function and structure. PMID- 11212947 TI - Numerical simulation and experimental validation of blood flow in arteries with structured-tree outflow conditions. AB - Blood flow in the large systemic arteries is modeled using one-dimensional equations derived from the axisymmetric Navier-Stokes equations for flow in compliant and tapering vessels. The arterial tree is truncated after the first few generations of large arteries with the remaining small arteries and arterioles providing outflow boundary conditions for the large arteries. By modeling the small arteries and arterioles as a structured tree, a semi analytical approach based on a linearized version of the governing equations can be used to derive an expression for the root impedance of the structured tree in the frequency domain. In the time domain, this provides the proper outflow boundary condition. The structured tree is a binary asymmetric tree in which the radii of the daughter vessels are scaled linearly with the radius of the parent vessel. Blood flow and pressure in the large vessels are computed as functions of time and axial distance within each of the arteries. Comparison between the simulations and magnetic resonance measurements in the ascending aorta and nine peripheral locations in one individual shows excellent agreement between the two. PMID- 11212948 TI - Method for assessing the need for case-specific hemodynamics: application to the distribution of vascular permeability. AB - A common approach to understanding the role of hemodynamics in atherogenesis is to seek relationships between parameters of the hemodynamic environment, and the distribution of tissue variables thought to be indicative of early disease. An important question arising in such investigations is whether the distributions of tissue variables are sufficiently similar among cases to permit them to be described by an ensemble average distribution. If they are, the hemodynamic environment needs be determined only once, for a nominal representative geometry; if not, the hemodynamic environment must be obtained for each case. A method for classifying distributions from multiple cases to answer this question is proposed and applied to the distributions of the uptake of Evans blue dye labeled albumin by the external iliac arteries of swine in response to a step increase in flow. It is found that the uptake patterns in the proximal segment of the arteries, between the aortic trifurcation and the ostium of the circumflex iliac artery, show considerable case-to-case variability. In the distal segment, extending to the deep femoral ostium, many cases show very little spatial variation, and the patterns in those that do are similar among the cases. Thus the response of the distal segment may be understood with fewer simulations, but the proximal segment has more information to offer. PMID- 11212949 TI - Finite element modeling of diffusion and partitioning in biological systems: the infinite composite medium problem. AB - Four methods are proposed for modeling diffusion in heterogeneous media where diffusion and partition coefficients take on differing values in each subregion. The exercise was conducted to validate finite element modeling (FEM) procedures in anticipation of modeling drug diffusion with regional partitioning into ocular tissue, though the approach can be useful for other organs, or for modeling diffusion in laminate devices. Partitioning creates a discontinuous value in the dependent variable (concentration) at an intertissue boundary that is not easily handled by available general-purpose FEM codes, which allow for only one value at each node. The discontinuity is handled using a transformation on the dependent variable based upon the region-specific partition coefficient. Methods were evaluated by their ability to reproduce a known exact result, for the problem of the infinite composite medium (Crank, J. The Mathematics of Diffusion, 2nd ed. New York: Oxford University Press, 1975, pp. 38-39.). The most physically intuitive method is based upon the concept of chemical potential, which is continuous across an interphase boundary (method III). This method makes the equation of the dependent variable highly nonlinear. This can be linearized easily by a change of variables (method IV). Results are also given for a one dimensional problem simulating bolus injection into the vitreous, predicting time disposition of drug in vitreous and retina. PMID- 11212950 TI - Delayed activation and retrograde propagation in cardiac muscle: implication of virtual electrode effects. AB - Point cathodal stimulation of cardiac tissue was shown previously to produce both a dog-bone shaped virtual cathode transverse to the muscle fibers and two longitudinal virtual anodes. We hypothesize that virtual anodes can cause a region of delayed activation, separating two regions of early activation caused by the virtual cathode. Using a high-density electrode array in 42 superfused epicardial slices from 14 canine left ventricles, we observed regions of early and delayed activation and different pathways of retrograde propagation corresponding to the earlier patterns. Retrograde propagation was seen from the transversely located early activation area through areas of delayed activation toward the cathode, and from the early activation area toward the cathode directly. These pathways caused a wide dispersion in the direction of retrograde propagation (2 degrees +/- 31 degrees, n = 179, relative to the fast axis of threshold activation; radial velocity: 0.5 +/- 0.2 m/s, n = 95, in 12 slices from 8 hearts with stimuli of 330 micros, 0.8-30 mA). Delayed activations were observed 0 degrees +/- 6 degrees (n = 32) from the axis in 23 maps (at differing stimulation strengths) recorded in 13 slices from 10 hearts. We conclude that point cathodal stimulation induce delayed activation along the fiber axis and retrograde propagation both along and transverse to the axis. PMID- 11212951 TI - Anisotropic mechanisms for multiphasic unipolar electrograms: simulation studies and experimental recordings. AB - The origin of the multiple, complex morphologies observed in unipolar epicardial electrograms, and their relationships with myocardial architecture, have not been fully elucidated. To clarify this problem we simulated electrograms (EGs) with a model representing the heart as an anisotropic bidomain with unequal anisotropy ratio, ellipsoidal ventricular geometry, transmural fiber rotation, epi endocardial obliqueness of fiber direction and a simplified Purkinje network. The EGs were compared with those directly recorded from isolated dog hearts immersed in a conducting medium during ventricular excitation initiated by epicardial stimulation. The simulated EGs share the same multiphasic character of the recorded EGs. The origin of the multiple waves, especially those appearing in the EGs for sites reached by excitation wave fronts spreading across fibers, can be better understood after splitting the current sources, the potential distributions and the EGs into an axial and a conormal component and after taking also into account the effect of the reference or drift component. The split model provides an explanation of humps and spikes that appear in the QRS (the initial part of the ventricular EG) wave forms, in terms of the interaction between the geometry and direction of propagation of the wave front and the architecture of the fibers through which excitation is spreading. PMID- 11212953 TI - Relations between components of impedance cardiogram analyzed by means of finite element model and sensitivity theorem. AB - The main aim of the study is to establish a relation between different sources of Impedance cardiogram (ICG) as function of spatial distribution of conductivity. A three-dimensional model of a human thorax using the finite element method has been constructed. The model includes 35 horizontal layers consisting of up to 519 pentahedral elements that are automatically divided into tetrahedral ones before calculating the potential distribution. Electrode array configuration proposed by Kubicek et al. (Aerosp. Med. 37: 1208-1212, 1996) has been studied. A relationship proposed by Geselowitz (IEEE Trans. Biomed. Eng. 18: 38-41, 1971) has been used to calculate the sensitivity of the examined electrode array to conductivity changes inside the thorax. This relationship has allowed for the calculation of the contributions to ICG from spatially separated sources when modeling all changes in conductivity simultaneously. It has been confirmed that the main contributions to ICG signal come from ventricles, atria, aorta, and lungs. The relations between these components have been found to be dependent nonlinearly on spatial conductivity distribution. As a result, reliable and reproducible measurements of stroke volume (SV) using ICG are impossible. Nevertheless, ICG can be used to monitor relative changes of SV in all cases where the spatial distribution of conductivity and geometry of the subject, during the examination, is preserved. However, it does not mean that the accuracy of SV measurement will be the same in all these cases. PMID- 11212952 TI - Ectopic activity in ventricular cells induced by early afterdepolarizations developed in Purkinje cells. AB - The development of early afterdepolarizations (EADs) in Purkinje fibers and their propagation to ventricular muscle cells are studied by computer modeling. The Purkinje-ventricular system has been simulated by a two-dimensional model of a Purkinje fiber (PF) connected to a thin sheet of ventricular muscle tissue (VMT). EADs are induced in the PF by enhancing the fast second inward current, iCa,f, and blocking the delayed K+ current, iK, while the VMT is kept under physiological conditions. Different phenomena are observed depending on the EAD conditions applied. For 70% iK blockade and iCa,f enhancement greater than 60%, a single phase 3 EAD developed in the PF propagates to the VMT generating an ectopic beat. For 80% iK blockade and iCa,f enhancement in the range from 0% to 70%, multiple ectopic beats appear in the VMT. However, for iK blockades over 80%, action potentials in PF cells do not repolarize and the ectopic activity in the VMT disappears. In our simulations, the ionic mechanism underlying phase 3 EAD development is the reactivation of the fast sodium current in the PF. Our results demonstrate that there exists a critical range of EAD conditions that favor the development of EADs in the PF and their propagation to the VMT as ectopic activity. This phenomenon could underlie the genesis of some triggered arrhythmias. PMID- 11212954 TI - EEG spike detection with a Kohonen feature map. AB - Artificial neural networks are widely used for pattern recognition tasks. For spike detection in electroencephalography (EEG), feedforward networks trained by the backpropagation algorithm are preferred by most authors. Opposed to this, we examined the off-line spike detection abilities of a Kohonen feature map (KFM), which is different from feedforward networks in certain aspects. The EEG data for the training set were obtained from patients with intractable partial epilepsies of mesiotemporal (n=2) or extratemporal (n=2) origin. For each patient the training set for the KFM included the same patterns of background activity and artifacts as well as the typical individual spike patterns. Three different-sized networks were examined (15 x 15 cells, 25 x 25 cells, and 60 x 60 cells in the Kohonen layer). To investigate the quality of spike detection the results obtained with the KFM were compared with the findings of two board-certified electroencephalographers. Application of a threshold based on the partial invariance of spike recognition against translation of the EEG provided an average sensitivity and selectivity of 80.2% at crossover threshold (71%-86%) depending on the networksize and noise. Multichannel EEG processing in real time will be available soon. In conclusion, pattern-based automated spike detection with a KFM is a promising approach in clinical epileptology and seems to be at least as accurate as other more-established methods of spike detection. PMID- 11212955 TI - Effect of supraglottic mechanoreceptors on spatial mapping of respiratory related evoked responses using wavelet and Laplacian methods. AB - Respiratory related evoked potentials (RREPs) were recorded from eight normal subjects in response to brief pressure pulses of -10 cm H2O with a duration of 200 ms to identify the contribution of supralaryngeal mechanoreceptors to the evoked responses by constraining application of the stimulus to the larynx and sublaryngeal regions through insertion of a laryngeal mask airway (LMA). Wavelet decomposition of RREP responses from 30 electrodes on the right side of the scalp was performed for eight frequency scales in time. The RREPs at each wavelet scale were enhanced by eliminating the wavelet coefficients due to artifacts and noise. After denoising, the third (125-150 Hz), fourth (62.5-125 Hz), fifth (31.25-62.5 Hz) and sixth (13.62-31.25 Hz) wavelet scales were used for estimation of the Laplacian. In addition, the global field power was calculated to quantify the wavelet-filtered RREP activity and to extract features for statistical analysis. Our results show that estimates of the global field power at the fourth and fifth wavelet scales are more significantly decreased after the insertion of the LMA than was true for scales 3 and 6. Further, after the LMA was inserted, the Laplacian showed reduced activity in the posterior-lateral region in four subjects and reductions in other places in the rest. PMID- 11212956 TI - A spherical rotation coordinate system for the description of three-dimensional joint rotations. AB - Three-dimensional joint rotations in human movement analysis have been mainly described by Euler/Cardan angles. Due to sequence dependence, each combination of three Euler/Cardan angles defines a single pattern of joint rotation. When the rotation pattern is unknown, it needs to be considered using a particular sequence of Euler/Cardan angles to represent joint rotations. In this paper a spherical rotation coordinate system is developed for describing three dimensional joint rotations using a method of rotation involving two steps: a long axis rotation and a pure axial rotation. Two angles of the classical spherical coordinate system--longitude and latitude--are used to describe long axis rotations in this newly proposed coordinate system. The spherical rotation coordinate system uses a radial rotation angle to describe pure axial rotation of a limb segment whereas the classical spherical coordinate system uses a radial displacement to describe motion of a point. An application of the spherical rotation coordinate system is given to define three-dimensional rotations of the glenohumeral joint. A mathematical proof shows that the long axis rotation and axial rotation are sequence independent. Two numerical examples are investigated which demonstrate that the spherical rotation angles can be uniquely determined in both forward and inverse kinematics without considering sequences rotations. PMID- 11212957 TI - Comparison of particle image velocimetry and laser Doppler anemometry measurements in turbulent fluid flow. PMID- 11212958 TI - Arterial hypertension and cardiac arrhythmias. AB - PURPOSE AND DATA IDENTIFICATION: One of the main clinical problems of patients with arterial hypertension is the presence of arrhythmias, especially if left ventricular hypertrophy exists. Recent results from our group and all data available via Med-Line-search have been analysed. The analysis was focused on atrial and ventricular arrhythmias and arrhythmic risk prediction, using non invasive markers. RESULTS OF ANALYSIS AND CONCLUSION: Arterial hypertension is a major cause of non-rheumatic atrial fibrillation and other supraventricular arrhythmias. The prevalence of ventricular arrhythmias is increased in hypertensive patients without left ventricular hypertrophy, compared to normotensives. If left ventricular hypertrophy is present, the risk for ventricular tachycardias is quadrupled. The presence of left ventricular hypertrophy is associated with an increase in all-cause mortality by a factor of seven in men and nine in women. In particular, patients with hypertrophy, increased rate of ventricular extrasystoles up to non-sustained ventricular tachycardia and ST-depression in long-term ECG are threatened by sudden cardiac death. At present, it is not possible to safely identify patients with increased risk. Regression of hypertrophy exists along with a decreased rate of ventricular extrasystoles. We hypothesize that by the regression of hypertrophy, the prevalence of sustained ventricular tachycardia decreases and therefore the prognosis of those patients can be improved, although controlled studies are not yet available. PMID- 11212959 TI - Usefulness of home blood pressure measurements in assessing the effect of treatment in a single-blind placebo-controlled open trial. AB - OBJECTIVES: Reproducibility of home blood pressure measurements (HBP), and the placebo effect on HBP, were examined to establish the number of subjects required in order to observe a significant antihypertensive effect of a drug for a comparative study between placebo and active treatment. METHODS: Reproducibility of HBP (n = 172 for systolic blood pressure and n = 137 for diastolic blood pressure) and the placebo effect on HBP (n = 35 for systolic and n = 42 for diastolic blood pressure) were examined using a semi-automatic electronic device on untreated hypertensive subjects during 21 consecutive days of measurements. From these two studies, the number of subjects required in order to observe a significant antihypertensive drug effect was assessed. In both studies, measurements from the first 3 days were excluded from the analysis. RESULTS: Reproducibility, defined as the difference between the initial 5 day average (days 4-8) and the last 5 day average (days 17-21) was -1.9 +/- 7.0/-1.4 +/- 4.8 mmHg (mean +/- SD), indicating high reproducibility with a minimal regression to the mean effect. A placebo was administered after the 8 day run-in period. The difference between the initial 5 day average (days 4-8) and the last 5 day average (days 17-21) was compared. The mean difference was 1.1 +/- 6.2/0.2 +/- 5.7 mmHg, suggesting that there was a minimal, if any, placebo effect. As determined by the power calculations, based on the standard deviations of the tests for reproducibility and the placebo effect, nine of 13 subjects are required to show that a 9/5 mmHg decrease in systolic HBP/diastolic HBP (50% of estimated effective decrease in systolic HBP/diastolic HBP according to the guidelines for clinical trials in Japan) is statistically significant CONCLUSIONS: The results suggest that the HBP measurement is highly reproducible and that there is a minimal, if any, placebo effect. These characteristics of HBP contribute to minimizing the number of subjects necessary for assessment of antihypertensive drug effects in comparative studies between an active treatment and placebo. PMID- 11212960 TI - Risks of smoking in treated and untreated older Chinese patients with isolated systolic hypertension. AB - OBJECTIVES: To examine the health risks associated with smoking and blood pressure in Chinese hypertensive patients and to compare the benefit of antihypertensive drug treatment with the risk attributable to smoking. METHODS: We used multiple Cox regression to correlate outcome with blood pressure and smoking status in 2284 older (aged > or = 60 years) patients enrolled in the Systolic Hypertension in China (Syst-China) Trial (systolic/diastolic blood pressure > or = 160/< 95 mmHg). RESULTS: Median follow-up was 3.0 years. After adjustment for sex, age, active antihypertensive treatment and various entry characteristics, the relative hazard rates associated with smoking more than 20 cigarettes per day were 2.04 (P = 0.04), 4.66 (P < 0.001) and 4.74 (P = 0.002) for all-cause, noncardiovascular and cancer mortality, respectively. With similar adjustments applied, the relative hazard rates for total (fatal and non-fatal) stroke associated with smoking 10-20 and more than 20 cigarettes per day were 1.78 (P = 0.04) and 2.23 (P = 0.03), respectively. Furthermore, both smoking and systolic blood pressure were associated with higher risk of stroke. Compared with the overall risk in the whole group, treating 1,000 patients for 5 years prevented 40 [95% confidence interval (CI), 5-75] strokes in smokers as well as never smokers. Prognosis in never smokers and past smokers was similar. Quitting smoking had the potential to prevent 51 (95% CI, -21 to 122) strokes in untreated hypertensive patients and to prevent 45 (95% CI, - 14 to 104) additional strokes in treated patients, over and above the effects of antihypertensive treatment. If, in addition to stroke, non-cardiovascular mortality was also accounted for, the estimated absolute benefit of quitting smoking increased to 69 (95% CI, -18 to 155) and 97 (95% CI, 23-171) events in the untreated and the treated group, respectively. CONCLUSIONS: In elderly Chinese patients, smoking was a risk factor for all-cause, non-cardiovascular and cancer mortality, as well as fatal and non fatal stroke. The potential benefits of antihypertensive treatment and quitting smoking were approximately similar. In our view, these findings are important in terms of public health policies and health economics. PMID- 11212961 TI - Involvement of erythropoietin-induced cytosolic free calcium mobilization in activation of mitogen-activated protein kinase and DNA synthesis in vascular smooth muscle cells. AB - BACKGROUND/OBJECTIVE: Human recombinant erythropoietin (rHuEPO) induces cytosolic free calcium ([Ca2+]i) mobilization, an activation of mitogen-activated protein (MAP) kinase and DNA synthesis in several tissues. We explored the mechanism of rHuEPO-induced [Ca2+]i mobilization and its role in the activation of MAP kinase and DNA synthesis in vascular smooth muscle cells (VSMC). METHODS: [Ca2+]i concentrations were measured by fura-2. MAP kinase activation was analyzed using an immunocomplex kinase assay and Western blotting. DNA synthesis was measured as an incorporation of 5-bromo-2'-deoxyuridine. RESULTS: Although addition of rHuEPO significantly increased [Ca2+]i, either in the presence or absence of extracellular Ca2+, the peak level and sustained elevation of [Ca2+]i were significantly reduced in the absence of extracellular Ca2+. Pretreatment with genistein completely blocked the elevation of [Ca2+]i in both conditions. Calphostin C and staurosporine did not completely block the elevation of [Ca2+]i. Staurosporine reduced its peak level in a dose-dependent manner, whereas calphostin C reduced its peak level at concentrations over 1 nmol/l in the presence of extracellular Ca2+. Similar results to those with staurosporine were observed with nifedipine. In the absence of extracellular Ca2+, their dose dependent effects disappeared even though rHuEPO increased [Ca2+]i. rHuEPO activated MAP kinase and DNA synthesis, both of which were significantly suppressed by the chelation of intracellular Ca2+. CONCLUSION: These findings suggest that rHuEPO increases [Ca2+]i by both Ca2+ influx and Ca2+ release from intracellular stores. Tyrosine phosphorylation is critical in the regulation of [Ca2+]i, but protein kinase C activation is important only in the regulation of Ca2+ influx. Dihydropyridine-sensitive L-type Ca2+ channels seem to be involved in rHuEPO-induced Ca2+ influx. In addition, increase of [Ca2+]i by rHuEPO stimulates MAP kinase activation and DNA synthesis in VSMC. PMID- 11212962 TI - Inhibition of vascular smooth muscle cell proliferation by DNA-RNA chimeric hammerhead ribozyme targeting to rat platelet-derived growth factor A-chain mRNA. AB - BACKGROUND: Spontaneously hypertensive rats (SHR)-derived vascular smooth muscle cells (VSMC) show exaggerated growth and increasingly express platelet-derived growth factor (PDGF) A-chain mRNA compared to VSMC from normotensive Wistar-Kyoto (WKY) rats. OBJECTIVE: To investigate the effects of designed DNA-RNA chimeric hammerhead ribozyme to rat PDGF A-chain on exaggerated growth of VSMC from SHR. DESIGN AND METHODS: We designed and synthesized a 38-base DNA-RNA chimeric hammerhead ribozyme with two phosphorothioate linkages at the 3' terminal to cleave rat PDGF A-chain mRNA at the GUC sequence at nucleotide 921. We confirmed the cleavage activity of designed ribozyme by in vitro cleavage reaction and by lipofectin-mediated transfection of ribozyme into VSMC. RESULTS: Doses of 0.1 and 1 micromol/l DNA-RNA chimeric ribozyme dose-dependently inhibited basal DNA synthesis in VSMC from SHR. A dose of 1 micromol/l DNA-RNA chimeric ribozyme time dependently inhibited basal DNA synthesis in VSMC from SHR. However, the same doses of all-RNA ribozyme had no effects on DNA synthesis in VSMC from SHR. Fluorescein isothiocyanate-labeled DNA-RNA chimeric ribozyme was recognized in cytosol at 30 min, and in nucleus at 60 min after lipofectin transfection. A dose of 1 micromol/l DNA-RNA chimeric ribozyme significantly inhibited expressions of both PDGF A-chain mRNA and PDGF-AA protein in VSMC from SHR, but not from WKY rats. CONCLUSION: These results indicated that the designed DNA-RNA chimeric ribozyme to PDGF A-chain mRNA effectively and specifically inhibited the exaggerated growth of VSMC from SHR at low concentrations, which were mediated by the reduction of PDGF A-chain mRNA and PDGF-AA protein expressions. PMID- 11212963 TI - Peripheral arterial vascular function at altitude: sea-level natives versus Himalayan high-altitude natives. AB - OBJECTIVES: Regulation of the vascular system may limit physical performance and contribute to adaptation to high altitude. We evaluated vascular function in 10 Himalayan high-altitude natives and 10 recently acclimatized sea-level natives at an altitude of 5,050 m. METHODS: We registered electrocardiogram, blood flow velocity in the common femoral artery, and blood pressure in the radial artery using non-invasive methods under baseline conditions, and during maximal vasodilation after 2 min leg occlusion. Vascular mechanics were characterized by estimating pulse wave velocity and input impedance. RESULTS: Pulse wave velocity and parameters of input impedance did not differ between groups under baseline conditions. In the post-ischemic period, the ratio between maximal hyperemic and baseline blood flow velocity was significantly higher in the high-altitude than in the sea-level natives (5.7 +/- 2.5 versus 3.8 +/- 1.2, P < 0.05). The leg vascular resistance decreased in the post-occlusive period without differences between groups. Characteristic impedance decreased in the post-ischemic period by about one third of the baseline level without differences between groups. The post-ischemic decrease of input impedance modulus was more marked in the high altitude than in the sea-level natives at low frequencies (28 +/- 12 versus 6.4 +/- 20% at 2 Hz, P < 0.01). CONCLUSIONS: Our results demonstrate a superior ability to increase blood flow velocity as a response to muscular ischemia in high-altitude natives compared to sea-level natives. This phenomenon may be associated with a more effective coupling between blood pressure and blood flow which is probably caused by differences in conduit vessel function. PMID- 11212964 TI - Angiotensin converting enzyme protects acetylcholine-induced relaxation from its attenuation by formyl-methionyl-leucyl-phenylalanine in rat aorta. AB - OBJECTIVE: A chemotactic tripeptide formyl-methionyl-leucyl-phenylalanine (fMLP) attenuated acetylcholine (ACh)-induced relaxation. Because angiotensin converting enzyme (ACE), which inactivates fMLP, is rich in vascular endothelial cells, we examined whether endothelial cell ACE inhibits the attenuating effect of fMLP on ACh-induced relaxation. DESIGN AND METHODS: ACh-induced relaxation was evaluated in aortic rings from 9-week-old Sprague-Dawley rats. We examined the effects of ACE, the ACE inhibitor captopril and/or fMLP on ACh-induced relaxation in aortas from rats with or without dexamethasone treatment, which enhances ACE activity. RESULTS: Pre-treatment with ACE did not alter ACh-induced relaxation in control aortas but abolished the inhibitory effect of fMLP on ACh-induced relaxation [maximal relaxation (Emax): 95.4 +/- 1.2 versus 75.5 +/- 1.9%, P < 0.05]. Conversely, captopril enhanced the attenuation of ACh-induced relaxation by fMLP (Emax: 62.5 +/- 3.3 versus 74.0 +/- 2.2%, P < 0.05), although captopril did not affect ACh-induced relaxation in control aortas. In addition, fMLP did not attenuate ACh-induced relaxation in aortas from dexamethasone-treated rats (Emax: 89.7 +/- 3.7 versus 85.2 +/- 3.8%, NS), which enhanced ACE activity of aortas (3.37 +/- 0.25 versus 2.70 +/- 0.20 IU/mg protein, P < 0.05). CONCLUSION: Endothelial-cell ACE attenuates the effect of fMLP on ACh-induced relaxation, possibly by its cleavage. PMID- 11212965 TI - Identification of endogenous ouabain in culture supernatant of PC12 cells. AB - OBJECTIVE: Ouabain-like factor (OLF), assayed as ouabain-like immunoreactivity (OLI), is thought to represent an endogenous digitalis-like factor. We found increased plasma OLI during the surgical removal of a pheochromocytoma. The elution volume of the OLI extracted from plasma and the pheochromocytoma tissue was the same as that for authentic ouabain, using reverse phase high-performance liquid chromatography. The present study was performed to characterize OLF from the culture supernatant of a rat pheochromocytoma cell line, PC12 cells. DESIGN: OLI from culture supernatant and chromatographic fractions were assayed by a sensitive enzyme-linked immunosorbent assay for ouabain. PC12 cells, subcultured in RPMI 1640 with 10% horse serum and 5% fetal bovine serum, were washed, and then cultured in Iscove's modified Dulbecco's medium (Life Technologies, Rockville, Maryland, USA) with 0.4% bovine serum albumin (without serum). Progesterone was added to augment the production or secretion of OLI. The conditioned medium was acidified to dissociate the binding protein, and OLI was purified by five steps of octadecylsilane (ODS) column chromatography. The structural identity of this OLI was determined by liquid chromatography and mass spectrometry (LC/MS). RESULTS: OLI in the culture medium increased after addition of progesterone in a dose-dependent manner. The concentration in the culture medium was approximately double of that in homogenized PC12 cells. After five rounds of ODS column chromatography, approximately 100 ng of OLI was purified from 21 of culture supernatant, without fetal calf serum, in the presence of progesterone. The molecular size of purified OLI was found to be identical to authentic ouabain, based on analysis by LC/ MS. CONCLUSION: Mammalian cells originating from a rat pheochromocytoma cell line were found to produce and/or secrete OLF by the addition of progesterone. PMID- 11212966 TI - A novel assay for determination of diadenosine polyphosphates in human platelets: studies in normotensive subjects and in patients with essential hypertension. AB - OBJECTIVE: Diadenosine polyphosphates (APnAs, n = 3-6) are a family of endogenous vasoactive purine dinucleotides which have been isolated from thrombocytes. Diadenosine pentaphosphate (AP5A) and diadenosine hexaphosphate (AP6A) are more potent than diadenosine tetraphosphate (AP4A) and diadenosine triphosphate (AP3A) and cause skeletal muscle vasoconstriction in rats. Little is known about their physiological and pathophysiological significance in humans. The aims of the present study were to compare thrombocyte APnA concentrations in patients with essential hypertension (HYP) and in healthy normotensive humans (CON) using a novel quantitative assay and to assess a possible relationship between thrombocyte APnA concentrations and skeletal muscle vascular resistance. DESIGN AND METHODS: We describe a novel assay for quantification of APnAs in human platelets, involving platelet isolation from human blood, a solid-phase extracting procedure with a derivatized resin, desalting and quantitative determination of the substances with an ion-pair reversed-phase high-performance liquid chromatography (HPLC) system. The structural integrity of the isolated APnAs was confirmed by mixed assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) measurements and co-elution with added standards. The detection threshold for all four APnAs was 1 pmol/l and the inter-assay coefficients of variation were < 11% (n = 12). After venous blood sampling, mean arterial blood pressure (MAP) and forearm blood flow (FBF, using venous occlusion plethysmography) were measured in HYP and CON. Forearm vascular resistance (FVR) was calculated as MAP/FBF. significantly differ in platelet AP3A and AP4A content, but HYP had significantly higher thrombocyte concentrations of AP5A (56 +/- 7 versus 32 +/- 3 ng/microg beta-thromboglobulin, P = 0.003) and AP6A (10 +/- 1 versus 6 +/- 1 ng/microg beta-thromboglobulin, P = 0.015) than CON. HYP had significantly elevated FVR (50 +/- 6 versus 33 +/- 2 arbitrary units, P = 0.01) compared to CON. Significant correlations were found between AP5A and FVR (p = 0.38, P = 0.04) as well as between AP6A and FVR (p = 0.42, P = 0.02). In contrast, there were no significant correlations between APnAs and MAP. CONCLUSIONS: The study shows that thrombocyte concentrations of AP5A and AP6A are elevated in patients with essential hypertension. Vasoconstriction caused by release of AP5A and AP6A from thrombocytes may contribute to the increase of vascular resistance in hypertensive patients. PMID- 11212967 TI - Relative deficiency of nitric oxide-dependent vasodilation in salt-hypertensive Dahl rats: the possible role of superoxide anions. AB - OBJECTIVE: The contribution of major vasoactive systems (renin-angiotensin system, sympathetic nervous system and nitric oxide) to blood pressure maintenance and the possible involvement of superoxide anions in the reduced efficiency of nitric oxide (NO)-dependent vasodilation to counterbalance sympathetic vasoconstriction were studied in salt-hypertensive Dahl rats. DESIGN AND METHODS: We used Dahl salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) female rats kept on a low-salt (0.3% NaCl) or high-salt diet (8% NaCl) for 6 weeks since weaning. Mean arterial pressure (MAP) was measured in conscious animals subjected to acute consecutive blockade of the renin-angiotensin system (RAS) [captopril, 10 mg/kg intravenously (i.v.)], the sympathetic nervous system (SNS) (pentolinium, 5 mg/kg i.v.) and NO synthase (Nomega-nitro-L-arginine methyl ester (L-NAME), 30 mg/kg i.v.). Before the consecutive blockade of vasoactive systems one-half of the animals in each experimental group was pre-treated with a stable membrane-permeable mimetic of superoxide dismutase (tempol, 25 mg/kg i.v.) which functions as a superoxide scavenger. RESULTS: Compared to normotensive SR/Jr animals, salt-hypertensive SS/Jr rats were characterized by an enhanced blood pressure (BP) fall after ganglionic blockade (-104 +/- 8 versus -62 +/- 5 mm Hg, P < 0.001) and by higher residual blood pressure recorded after the blockade of both RAS and SNS (70 +/- 3 versus 43 +/- 3 mmHg, P < 0.01), but there was only a borderline elevation of their BP response to acute NO synthase inhibition (67 +/- 6 versus 49 +/- 4 mmHg, P < 0.05). The acute tempol pre treatment elicited the most pronounced reduction of basal BP (-13 +/- 1 mmHg, P < 0.001) in the salt-hypertensive SS/Jr group in which the BP rise after L-NAME administration was augmented by about 50%. On the contrary, tempol pre-treatment did not affect norepinephrine- or angiotensin II-dependent vasoconstriction. CONCLUSIONS: The NO system is not able to counterbalance effectively the hyperactivity of the sympathetic nervous system in salt-hypertensive Dahl rats. The predominance of sympathetic vasoconstriction over NO-dependent vasodilation could be explained partially by enhanced NO inactivation due to augmented superoxide anion formation in hypertensive animals. PMID- 11212968 TI - Differential expression and synthesis of natriuretic peptides determines natriuretic peptide receptor expression in primary cultures of human proximal tubular cells. AB - INTRODUCTION: The natriuretic peptides and natriuretic peptide receptors may play a beneficial role in hypertension and heart failure and possibly in opposing associated detrimental cellular changes in the heart, vasculature and kidney. These responses may be, in part, modulated by the natriuretic peptide clearance receptor rather than the natriuretic peptide receptors (NPR-A or NPR-B). OBJECTIVE: To investigate the expression of the natriuretic peptide receptors (NPR-A,-B,-C) and the natriuretic peptides (ANP, BNP, CNP) in primary cultures of human proximal tubular cells and the role played by endogenously released natriuretic peptides in natriuretic peptide receptor expression. RESULTS: Northern analysis demonstrated that freshly isolated human proximal tubular cells express the NPR-C only. However, at confluence mRNA transcripts for both the NPR A and -B were expressed, accompanied by a significant cyclic guanosine monophosphate (cGMP) response to ANP and CNP, indicating the development of functionally active receptors. A significant increase in immunoreactive ANP, BNP and CNP in the cell supernatant accompanied the appearance of these receptors. Incubation of freshly isolated cells with exogenous ANP, BNP, CNP or with the NPR C specific ligand C(4.23)ANF induced similar changes in receptor expression, suggesting that these changes were mediated via the NPR-C rather than the NPR-A or -B. CONCLUSIONS: Significant changes in peptide and receptor expression occur during cell culture and may be integrally linked, with functionally active NPR-A and -B occurring in response to an increase in the expression of the natriuretic peptides possibly acting at the NPR-C. PMID- 11212969 TI - Effects of oral L-arginine on plasma nitrate and blood pressure in cortisol treated humans. AB - OBJECTIVE: The aim of this study was to determine whether cortisol-induced hypertension can be reversed by co-administration of oral L-arginine. STUDY DESIGN: Three studies were undertaken in healthy male human subjects. The first study addressed the effect of oral L-arginine loading on plasma arginine concentration. Study 2 addressed the effect of co-administration of cortisol with L-arginine on plasma L-arginine concentrations. Study 3 was a randomized placebo crossover control comparing the effects of cortisol 80 mg/day co-administered with a placebo to cortisol 80 mg/day co-administered with L-arginine 21 g/day. METHODS: Blood pressure was measured by a random Hawksley sphygmomanometer. Plasma nitrate/nitrite concentrations were measured by a modified Greiss reaction. Plasma arginine and citrulline concentrations were measured by an automated amino acid analyser. RESULTS: Plasma arginine concentrations were doubled by oral doses of 15 g/day and 21 g/day of L-arginine (study 1). Co administration of cortisol did not alter plasma arginine concentrations in subjects taking 21 g of L-arginine per day (study 2). Co-administration of L arginine 21 g/day with cortisol 80 mg/day did not prevent cortisol-induced increases in blood pressure or cortisol-induced falls in plasma nitrate/nitrite concentrations. CONCLUSION: Cortisol-induced hypertension is accompanied by a fall in plasma nitrate/nitrite concentrations. Oral L-arginine administration does not prevent cortisol-induced falls in plasma nitrate/nitrite concentrations or increases in blood pressure. We propose that cortisol-induced reductions in nitrate/nitrite production occur at a point distal to L-arginine availability in the nitric oxide synthase pathway. PMID- 11212970 TI - Hormone replacement improves hemodynamic profile and left ventricular geometry in hypertensive and normotensive postmenopausal women. AB - BACKGROUND: Postmenopausal estrogen replacement, with or without progestins, has been related to lower cardiovascular risks. OBJECTIVE: We investigated whether the actions of estrogen on vascular resistance contribute to this cardioprotective effect. DESIGN AND METHODS: In a 6-month double-blind study, pre and post-treatment blood pressure, cardiac index, total vascular resistance index and plasma catecholamine responses during baseline and mental stressors were compared in 69 women (including 19 with mild hypertension but no history of heart disease). Women were randomized to receive either conjugated estrogens alone, estrogens plus medroxyprogesterone, or placebo. RESULTS: Both groups on active hormone replacement showed similar decreases in vascular resistance and modest blood pressure reductions, which differed from the unchanged responses of those on placebo (P< 0.05) after 3 and 6 months of treatment. Hypertensive women showed greater reductions in vascular resistance than normotensives (P< 0.05) and their blood pressure reductions tended to be larger. Women receiving hormone replacement showed increased stroke volume and cardiac index at 6 months, particularly among hypertensives and those receiving medroxyprogesterone (P < 0.05). Hormone replacement was also related to decreases in plasma norepinephrine. Finally, in 33 women receiving hormone replacement, significant 5 and 3% decreases in echocardiographic measures of left ventricular mass index and relative wall thickness were evident at 6 months (P < 0.05), while 20 placebo treated women showed no reliable echocardiographic improvements (P= NS). CONCLUSIONS: These findings suggest that estrogen-mediated reductions in hemodynamic load on the heart may contribute to the reduced risk of cardiovascular events in relatively healthy postmenopausal women who use hormone replacement. PMID- 11212972 TI - Left ventricular hypertrophy and nocturnal hypoxemia in hemodialysis patients. AB - OBJECTIVE: Nocturnal hypoxemia has recently been proposed as a cardiovascular risk factor in patients with chronic renal failure. In this study we have tested the hypothesis that this disturbance is associated with left ventricular hypertrophy (LVH) in dialysis patients. METHODS: During a mid-week non-dialysis day, 38 hemodialysis patients underwent continuous monitoring of arterial O2 saturation (SaO2) during night-time as well as 24 h ambulatory blood pressure monitoring and echocardiography. RESULTS: Eighteen patients had one or more episodes of O2 desaturation during night-time (average: 21 episodes; range 1 to 120) while the other 20 had no episode. Neither day-time arterial pressure nor heart rate were significantly associated with nocturnal hypoxemia. However there was a significant correlation between the night/day systolic ratio and the severity of hypoxemia during night-time (r = 0.36, P = 0.03). On multivariate analysis, nocturnal hypoxemia proved to be the stronger independent predictor of relative wall thickness, mean wall thickness and left ventricular mass index, suggesting that nocturnal O2 desaturation is linked to concentric hypertrophy and to concentric geometry of the left ventricle. Accordingly, the proportion of patients with such geometric alteration was higher (chi2 = 4.1, P = 0.04) in patients with a pulse oximetry severity score > 50th percentile [15 of 19 (79%)] than in those below this threshold [nine of 19 (47%)]. CONCLUSIONS: Nocturnal hypoxemia is an important correlate of LVH in hemodialysis patients. Such an association is largely independent of arterial pressure. These data further underscore the importance of disturbed respiratory control as a cardiovascular risk factor in dialysis patients. PMID- 11212971 TI - Comparative effects of mibefradil and nifedipine gastrointestinal transport system on autonomic function in patients with mild to moderate essential hypertension. AB - BACKGROUND: L-type dihydropyridine calcium channel blockers (CCBs) have been implicated in increased cardiovascular events in patients with hypertension, perhaps due to adverse effects on autonomic nervous system (ANS) function. Blockade of T-type calcium channels may limit ANS dysfunction by inhibition of T channel-mediated neuroendocrine effects. OBJECTIVE AND DESIGN: This double-blind, parallel group study compared the effect of nifedipine gastrointestinal transport system (GITS) (L-type CCB) versus mibefradil (T-type CCB) on ANS function in patients with mild-moderate essential hypertension. METHODS: Sixteen patients (10 male, 6 female; age 57.2 +/- 2.3 years), diastolic blood pressure (DBP) < 95 mmHg were randomized to nifedipine 30 mg daily or mibefradil 50 mg daily (2 weeks), then nifedipine 60 mg daily or mibefradil 100 mg daily (4 weeks). Sympathetic nervous system activity (SNSA) was assessed using norepinephrine kinetics. Parasympathetic nervous system activity (PSNA) was assessed from 24 h Holter recordings of heart rate variability (HRV). Non-invasive baroreflex sensitivity (BRS) provided integrated assessment of ANS. RESULTS: Patient groups were well matched at baseline. Achieved DBP was lower in patients treated with mibefradil compared with nifedipine, (83.4 +/- 1.7 versus 95.25 +/- 3.3 mmHg). There were no significant differences in SNSA and BRS between groups, however the root mean square of successive differences and high frequency power (HFP) were increased in mibefradil compared with nifedipine-treated patients [(+ 1.07 +/- 1.6 versus 3.36 +/- 1.2 ms, P < 0.05) and (+ 0.28 +/- 0.1 versus -0.23 +/- 0.1 ms2, P < 0.01), respectively]. Furthermore, Ln HFP/Ln total power was increased from week 0 to week 6 in the mibefradil-treated group, (0.71 +/- 0.02 versus 0.74 +/- 0.03, P = 0.046). CONCLUSION: No differences existed between effect of L- and T-type CCBs on SNSA and BRS. However, T-type CCBs increased PSNA, independent of achieved changes in heart rate. PMID- 11212973 TI - Increased incidence of myocardial infarction and stroke in hypertensive men with reduced lung function. AB - BACKGROUND AND OBJECTIVE: Although hypertension is associated with increased cardiovascular risk, many individuals remain free from disease. This study is aimed to investigate whether this variation in individual susceptibility is associated with lung function. DESIGN: Population-based prospective cohort study. PARTICIPANTS: 'Men born in 1914', Malmo, Sweden. Subjects (n = 639) were examined and considered free from prevalent cardiovascular disease at age 55 years. MAIN OUTCOME MEASURES: Mortality, fatal and non-fatal stroke and cardiac events (fatal or non-fatal myocardial infarction) during 28-years follow-up. RESULTS: Of the men, 467 had normal blood pressure and 172 (27%) had hypertension (> or = 160/95 mmHg or treatment for hypertension). Hypertensive men with height-adjusted forced expiratory volume during 1 s (FEV1.0) below median had significantly higher rates of stroke (13.4 versus 5.8/1,000 person-years), cardiac events (27.1 versus 12.8/1,000 person-years) and all cause mortality (52.5 versus 28.6/1,000 person years) than hypertensive men with high FEV1.0. These differences remained statistically significant after adjustment for potential confounders. Men with normal blood pressure and FEV1.0 below median had higher rates of stroke (5.4 versus 4.2/1,000 person-years), cardiac events (13.3 versus 11.6/1,000 person years) and all cause mortality (29.9 versus 21.2/1,000 person-years) than men with normal blood pressure and high FEV1.0. After adjustments for potential confounders, FEV1.0 was significantly associated with mortality among men with normal blood pressure, whereas the associations with stroke and cardiac events did not reach significance. CONCLUSION: The incidence of cardiovascular disease and death associated with hypertension is increased among men with reduced lung function. The synergistic interaction between hypertension and lung function was independent of smoking and other potential confounders. PMID- 11212975 TI - Left ventricular mass is not related to insulin sensitivity in never-treated primary hypertension. AB - OBJECTIVE: Insulin has been suggested to promote myocardial cell growth and the development of left ventricular (LV) hypertrophy. This study examines the possible relationship between LV mass and insulin sensitivity. DESIGN: Previously untreated non-diabetic hypertensive patients. PATIENTS: Fifty-one patients with mean age 51 +/- 8 years, body mass index (BMI) 25.9 +/- 3.2 kg/m2 and blood pressure 158/102 mmHg were included. LV mass was determined by echocardiography. Glucose metabolism was assessed by an euglycemic insulin clamp (40 mU/m2 body surface area/min). RESULTS: Insulin sensitivity index (MI) and insulin clearance were inversely related to LV mass (r = -0.37, P < 0.01 and -0.33, P < 0.05, respectively) and LV mass indexed to height (r = -0.33, P < 0.05 and -0.29, P < 0.05, respectively). C-peptide and fasting insulin were related to LV mass (r = 0.33, P < 0.05 and r = 0.36, P < 0.01, respectively) and LV mass indexed to height (r = 0.30, P < 0.05 and r = 0.34, P < 0.05, respectively). In contrast, when LV mass was indexed by body surface area there was no longer a relation to MI, insulin clearance, C-peptide or fasting insulin. When adjusting for BMI in a multiple regression analysis, MI and LV mass no longer showed a relation. Indeed, MI, insulin clearance, C-peptide and insulin were all strongly related to weight and BMI. CONCLUSION: Insulin sensitivity is related to body size in untreated hypertension. However, insulin sensitivity is not related to LV mass, if adjusting for body size. This does not support a direct growth-promoting effect of insulin on the myocardium. Insulin does not appear to be strongly involved in development of hypertensive LV hypertrophy. PMID- 11212974 TI - Long-term effects of amlodipine and lisinopril on left ventricular mass and diastolic function in elderly, previously untreated hypertensive patients: the ELVERA trial. AB - OBJECTIVE: To compare the effects of a calcium antagonist (amlodipine) and an angiotensin converting enzyme inhibitor (lisinopril) on left ventricular mass and diastolic function in elderly, previously untreated hypertensives. DESIGN: A double-blind randomized parallel group trial. Effects of amlodipine and lisinopril on left ventricular mass and diastolic function (E/A Ratio) (The ELVERA trial). SETTING: Rural northern Netherlands: population screening new diagnosed hypertensive subjects. PATIENTS: The study population comprised 166 newly diagnosed hypertensive (aged 60-75) with diastolic blood pressure between 95-115 mmHg and/or systolic blood pressure between 160-220 mmHg. INTERVENTION: Patients were randomly allocated to receive 5-10 mg amlodipine or 10-20 mg lisinopril for 2 years. MAIN OUTCOME MEASURES: Prior and after 1 and 2 years of treatment left ventricular mass, indexed by body surface (LVMI) was estimated by 2-D mode echocardiography according to Devereux with use of Penn convention. Early to atrial filling ratio (E/A) was assessed by transmitral flow. Change from baseline of LVMI and E/A ratio was evaluated by repeated measurement analysis of the treatment effect in an intention-to-treat analysis. RESULTS: Both amlodipine and lisinopril led to equivalent reduction in systolic and diastolic blood pressure. At the end of the study the amlodipine group led to LVMI decrease by 21.8 g/m < or = [95% confidence interval (CI), 18.3-25.3] and E/A ratio increased by 0.08 (95% CI, 0.05-0.11). In the lisinopril group LVMI decreased by 22.4 g/m < or = (95%, CI, 19.0-25.8) and E/A ratio increased by 0.07 (95% CI, 0.04-0.10). No statistically significant differences were found in changes in LVMI and E/A ratio between amlodipine and lisinopril. CONCLUSION: A long-term study, the ELVERA trial proves that amlodipine and lisinopril reduce left ventricular mass and improve diastolic function to a similar extent in elderly newly diagnosed hypertensive patients. PMID- 11212976 TI - Frequency and determinants of microalbuminuria in mild hypertension: a primary care-based study. AB - OBJECTIVE: To evaluate the frequency of microalbuminuria and its relationship with several risk factors and left ventricular mass in a population of mildly hypertensive subjects attended in a primary-care setting. DESIGN: Cross-sectional study. SETTING: Eight primary-care centres. PATIENTS: Two hundred and twenty three non-diabetic patients recently diagnosed with mild hypertension were included in the study. None of them had clinical evidence of target-organ damage or had received prior antihypertensive treatment. INTERVENTIONS: Subjects included in the study underwent clinical interview, measurement of blood pressure (BP) on three visits, blood analysis, measurement of albumin by immunonephelometry in three overnight urine collections, 24 h BP monitoring and M mode and Doppler echocardiography. MAIN OUTCOME MEASURES: Tobacco habit, clinic BP, body mass index, serum lipids and uric acid, glycaemia, urinary albumin excretion (UAE), ambulatory BP and left ventricular mass index. RESULTS: The frequency of microalbuminuria was 7.2%. Microalbuminuric patients were more likely to be men and to be characterized by higher ambulatory BP, body mass index and uric acid levels. Regression analysis demonstrated that male sex and 24 h systolic BP were determinants of UAE. Patients with white-coat hypertension showed lower UAE than did subjects with sustained hypertension. Although a certain relationship between UAE and left ventricular mass index was found, these variables were not significantly correlated. CONCLUSIONS: A low proportion of mildly hypertensive patients attended in a primary care setting are microalbuminuric. In this population, UAE is an expression of BP values over 24 h and correlates with several risk factors. PMID- 11212977 TI - Glomerular hypertension and hyperfiltration in adrenocorticotrophin-induced hypertension in rats: the role of nitric oxide. AB - OBJECTIVE: To determine the effects on pre- and post-glomerular vascular resistance of adrenocorticotrophin (ACTH)-induced hypertension in rats, before and after blockade of nitric oxide formation. DESIGN: Four groups of Sprague Dawley rats were studied. Measurements were made in ACTH- (Synacthen Depot, 0.25 mg/kg twice daily for 8 days) and sham-treated anaesthetized rats, before and after either Nomega-nitro-L-arginine (L-NNA, 6 mg/kg) or vehicle. METHODS: Whole kidney and single-nephron haemodynamics and function were measured. Glomerular capillary pressure was estimated from tubular stop-flow pressure measurements. RESULTS: Blood pressure (P < 0.001), renal blood flow (RBF, P < 0.05) and glomerular filtration rate (P < 0.01) were increased following ACTH treatment compared with sham. There were no differences in either total renal, or pre- or post-glomerular vascular resistances, but stop-flow-estimated glomerular capillary pressure was elevated (P < 0.001) as was single-nephron glomerular filtration rate (SNGFR) (P < 0.001) and single-nephron blood flow (P < 0.01 ) in the ACTH- compared to the sham-treated rats. L-NNA treatment increased blood pressure by a similar extent in both ACTH- and sham-treated rats, but reduced RBF (P < 0.05) and glomerular filtration rate (GFR) (P < 0.05) more in the ACTH group; similar changes were seen in single-nephron values. L-NNA increased pre- and post-glomerular resistances to a greater extent in the ACTH group. CONCLUSIONS: ACTH-induced hypertension produced glomerular hypertension and hyperfiltration, which may be due to nitric oxide-related vasodilatation of the renal vasculature. PMID- 11212978 TI - Electronic compliance monitoring in resistant hypertension: the basis for rational therapeutic decisions. AB - OBJECTIVE: Incomplete compliance is one of several possible causes of uncontrolled hypertension. Yet, non-compliance remains largely unrecognized and is falsely interpreted as treatment resistance, because it is difficult to confirm or exclude objectively. The goal of this study was to evaluate the potential benefits of electronic monitoring of drug compliance in the management of patients with resistant hypertension. METHODS: Forty-one hypertensive patients resistant to a three-drug regimen (average blood pressure 156/ 106 +/- 23/11 mmHg, mean +/- SD) were studied prospectively. They were informed that for the next 2 months, their presently prescribed drugs would be provided in electronic monitors, without any change in treatment, so as to provide the treating physician with a measure of their compliance. Thereafter, patients were offered the possibility of prolonging the monitoring of compliance for another 2 month period, during which treatment was adapted if necessary. RESULTS: Monitoring of compliance alone was associated with a significant improvement of blood pressure at 2 months (145/97 +/- 20/15 mmHg, P < 0.01). During monitoring, blood pressure was normalized (systolic < 140 mmHg or diastolic < 90 mmHg) in one-third of the patients and insufficient compliance was unmasked in another 20%. When analysed according to tertiles of compliance, patients with the lowest compliance exhibited significantly higher achieved diastolic blood pressures (P = 0.04). In 30 patients, compliance was monitored up to 4 months and drug therapy was adapted whenever necessary. In these patients, a further significant decrease in blood pressure was obtained (from 150/100 +/- 18/15 to 143/94 +/- 22/11 mmHg, P = 0.04/0.02). CONCLUSIONS: These results suggest that objective monitoring of compliance using electronic devices may be a useful step in the management of patients with refractory hypertension, as it enables physicians to take rational decisions based on reliable and objective data of drug compliance and hence to improve blood pressure control. PMID- 11212979 TI - A comparison of indapamide SR 1.5 mg with both amlodipine 5 mg and hydrochlorothiazide 25 mg in elderly hypertensive patients: a randomized double blind controlled study. AB - OBJECTIVE: To analyse the efficacy of indapamide sustained-release (SR) 1.5 mg in reducing blood pressure versus amlodipine 5 mg and hydrochlorothiazide 25 mg, in elderly hypertensive patients. DESIGN: Double-blind, randomized, 12 week study using three parallel groups. SETTING: European teaching hospitals and general practices. PATIENTS: Randomized patients, (n = 524) including 128 patients with isolated systolic hypertension (ISH); mean age: 72.4 years; mean systolic/diastolic blood pressures (SBP/DBP): 174.5/97.9 mmHg. MAIN OUTCOME MEASURES: Clinic systolic and diastolic blood pressure variations. RESULTS: Indapamide SR 1.5 mg demonstrates a similar efficacy to that of amlodipine 5 mg, as well as to that of hydrochlorothiazide 25 mg (equivalence P < 0.001); the mean decreases in SBP/DBP were -22.7/-11.8 mmHg, -22.2/-10.7 mmHg and -19.4/-10.8 mmHg, respectively. In the ISH subgroup, indapamide SR 1.5 mg tends to have greater efficacy than hydrochlorothiazide 25 mg in reducing the SBP (-24.7 versus -18.5 mmHg, respectively; equivalence P = 0.117), while similar results are obtained with amlodipine 5 mg (-23 mmHg, equivalence P < 0.001). The normalization rate was relatively high for indapamide SR 1.5 mg (75.3%), when compared with amlodipine (66.9%) and hydrochlorothiazide (67.3%), especially in the subgroup of isolated systolic hypertensive patients: 84.2 versus 80.0% for amlodipine, and versus 71.4% for hydrochlorothiazide. CONCLUSIONS: Indapamide SR 1.5 mg shows similar antihypertensive efficacy to amlodipine 5 mg and hydrochlorothiazide 25 mg in elderly hypertensive patients, while in patients with isolated systolic hypertension, indapamide SR 1.5 mg shows a similar efficacy to amlodipine 5 mg but a greater efficacy than hydrochlorothiazide 25 mg. PMID- 11212980 TI - Assessment of arterial and cardiopulmonary baroreflex gains from simultaneous recordings of spontaneous cardiovascular and respiratory variability. PMID- 11212981 TI - Epidural analgesia for labour and instrumental vaginal delivery: an anaesthetic problem with an obstetric solution? PMID- 11212982 TI - The frequency of significant pathology in women attending a general gynaecological service for postcoital bleeding. AB - OBJECTIVES: To document the frequency of pathology in women who complain of postcoital bleeding. To determine whether negative cervical cytology excludes serious pathology in women with postcoital bleeding. To determine whether postcoital bleeding increases the risk of serious pathology in women with an abnormal smear. DESIGN: A retrospective study. SETTING: A university teaching hospital. POPULATION: 314 women with postcoital bleeding seen in the gynaecology service from first January 1988 to 31 December 1994. METHODS: Women were identified from the computerised records of the colposcopy service and copies of correspondence, which was routinely retained on computer. The latter was searched for the text strings coital and intercourse. MAIN OUTCOME MEASURE: Histopathological diagnosis. RESULTS: Twelve women (4%) had invasive cancer: 10 were cervical or vaginal cancers and two endometrial cancers. Eight of the 10 cervical or vaginal cancers were clinically apparent. Four women of these 10 had had a normal smear before being referred for further investigation of postcoital bleeding. Two of these cancers were visible only with the aid of the colposcope. Thus, 0.6% of women attending a gynaecology service with postcoital bleeding, a normal looking cervix and a normal smear had invasive cancer of the cervix. Cervical intraepithelial neoplasia were found in 54 women (17.%) and 15 women (5%) had cervical polyps. Nineteen of the 63 women (30%) with significant pathology had a normal or inflammatory cervical smear. No explanation for the postcoital bleeding was found in 155 women (49 %). CONCLUSIONS: Although invasive cancer is rare in women with postcoital bleeding, it is much commoner than in the general population. It seems likely that cervical intraepithelial neoplasia is also associated with postcoital bleeding, perhaps because the fragile cervical epithelium becomes detached during intercourse. Postcoital bleeding should continue to be regarded as an indication of high risk for invasive cervical cancer and for cervical intraepithelial neoplasia. Prompt referral to a colposcopy clinic is indicated, but most women with postcoital bleeding will have no serious abnormality. PMID- 11212983 TI - Evaluating ambulatory urodynamics: a prospective study in asymptomatic women. AB - OBJECTIVE: To identify abnormal detrusor contractions in asymptomatic women undergoing ambulatory urodynamics, to standardise the investigation technique for women with urinary symptoms for clinical practice. DESIGN: Prospective observational study. SETTING: Two tertiary referral urogynaecology units: one in London, UK and one in Varese, Italy. METHODS: Women without urinary symptoms were recruited into the study. Ambulatory urodynamics was performed according to the King's College Hospital protocol. All the traces were analysed in four different ways: 1. without the second bladder transducer measurements displayed on the screen and without the diary; 2. as in 1. but with the diary; 3. with the second bladder sensor displayed on the screen but without the diary; 4. as in 3. but with the diary. The diary was always interpreted at the end of the test with the woman present. For each method we reported the total number of detrusor contractions and whether the woman would have been diagnosed as having abnormal detrusor contraction. Cochran's Q test was used for statistical analysis. RESULTS: Twenty-six women (mean age 31.7 years) were recruited. Ambulatory urodynamic testing lasted an average of 3.57 hour. The diagnosis of abnormal detrusor contraction varied by 65.4% depending on the method of analysis used. The diary and the women's symptoms during the test were the most discriminating factors. A significant difference between the diagnoses was obtained when comparing the four different ways of analysis. According to our protocol only three women (11.5%) had abnormal detrusor contractions. CONCLUSIONS: Using our protocol almost 90% of asymptomatic women have a stable bladder on ambulatory urodynamics. This is similar to the results of labouratory urodynamic testing of asymptomatic women but is in contrast to previous reports of ambulatory urodynamics of asymptomatic women. The technique used during ambulatory urodynamics determines the tests ability to detect detrusor instability with an accurate symptom diary being the most important. PMID- 11212984 TI - Non-surgical treatment of uterovaginal prolapse using double vaginal rings. AB - A new technique of using double vaginal ring pessaries to treat uterovaginal prolapse in a group of elderly women is described. Eighteen women with a mean age of 82 years and advanced Stage III or IV uterovaginal prolapse had double vaginal rings inserted. All of them previously had used single vaginal ring pessaries or had undergone pelvic floor repair surgery. Double ring pessaries were successful in 13 of the 18 women. They are a useful treatment of advanced prolapse in women unsuitable for surgery. PMID- 11212985 TI - Medical education with the Internet: a pilot training programme in reproductive medicine. AB - Following a detailed information technology survey in the South West Deanery, an Internet educational programme in reproductive medicine was constructed, delivered and assessed. The course followed a problem-based approach using case studies, using an education website and electronic mail (e-mail) to communicate between trainees and trainers. Independent evaluation revealed a high level of satisfaction for both trainees and trainers with an increase in trainees' confidence to deal with patients following the course. This study suggests that the Internet may be used effectively to deliver postgraduate medical education, if the training programme is designed appropriately to computer infrastructure and the computer literacy of the users. PMID- 11212986 TI - Conservative anterior exenteration with preservation of fertility potential and continent urinary diversion. PMID- 11212987 TI - Malignant rhabdoid tumour of the uterine cervix. PMID- 11212988 TI - Ureteric obstruction with mucocoele of the appendix due to endometriosis. PMID- 11212989 TI - Association of cerebral perfusion pressure with headache in women with pre eclampsia. PMID- 11212991 TI - Can diagnostic laparoscopy be avoided in routine investigation for infertility? PMID- 11212990 TI - Puerperal sepsis: a disease of the past? PMID- 11212992 TI - Randomised comparison of Burch colposuspension versus anterior colporrhaphy for patients with stress urinary incontinence. PMID- 11212993 TI - Guidelines in gynaecology: in menorrhagia and in urinary incontinence. PMID- 11212994 TI - Fertility following radical, conservative-surgical or medical treatment for tubal pregnancy: a population-based study. PMID- 11212995 TI - Decision to delivery for assisted vaginal vertex delivery. PMID- 11212996 TI - Decision to delivery for assisted vaginal vertex delivery. PMID- 11212997 TI - Fibroid embolisation: a technique not without significant complications. PMID- 11212998 TI - Collaboration in maternity care: a randomised controlled trial comparing community-based continuity of care with standard hospital care. AB - OBJECTIVE: To test whether a new community-based model of continuity of care provided by midwives and obstetricians improved maternal clinical outcomes, in particular a reduced caesarean section rate. DESIGN: Randomised controlled trial. SETTING: A public teaching hospital in metropolitan Sydney, Australia. Sample 1089 women randomised to either the community-based model (n = 550) or standard hospital-based care (n = 539) prior to their first antenatal booking visit at an Australian metropolitan public hospital. MAIN OUTCOME MEASURES: Data were collected on onset and outcomes of labour, antenatal, intrapartum and postnatal complications, antenatal admissions to hospital and neonatal mortality and morbidity. RESULTS: There was a significant difference in the caesarean section rate between the groups, 13.3% (73/550) in the community-based group and 17.8% in the control group (96/539). This difference was maintained after controlling for known contributing factors to caesarean section (OR = 0.6, 95% CI 0.4-0.9, P = 0.02). There were no other significant differences in the events during labour and birth. Eighty babies (14.5%) from the community-based group and 102 (18.9%) from the control group were admitted to the special care nursery, but this difference was not significant (OR 0.75, 95% CI 0.5-1.1, P = 0.12). Eight infants died during the perinatal period (four from each group), for an overall perinatal mortality rate of 7.3 per 1000 births. CONCLUSION: Community-based continuity of maternity care provided by midwives and obstetricians resulted in a significantly reduced caesarean section rate. There were no other differences in clinical outcomes. PMID- 11212999 TI - A comparison of oral and vaginal misoprostol for induction of labour at term: a randomised trial. AB - OBJECTIVE: To compare the efficacy of oral with vaginal misoprostol for induction of labour at term. DESIGN: Randomised trial. SETTING: Tertiary Care hospital. PARTICIPANTS: One hundred and sixty-seven women requiring induction of labour. METHODS: The women were randomised to receive 50 microg of misoprostol orally or vaginally every 6 h until the cervix was favourable for amniotomy, spontaneous rupture of membranes, or active labour occurred. Sample size was calculated with a two-tailed alpha of 0.05 and a power of 95% to detect a 5 h difference in induction-to-delivery time. Student's t test was used for comparison of normally distributed continuous variables and the Mann-Whitney U test was used for non Gaussian distributed continuous variables. Fisher' s exact and chi2 tests were used for comparison of categorical variables. The main outcome measure was induction to delivery time. RESULTS: The median induction to delivery time was significantly shorter with vaginal misoprostol (15.7 h range 4.3-55.7), compared with oral misoprostol (23.0 h range 3.2-141.7, P = 0.0013). The median number of doses was also significantly less in the vaginal misoprostol group, 1 (range 1 3), compared with the oral group, 2 (range 1-8), (P < 0.0001). The significant differences in outcome held true when nulliparous and multiparous women were analysed separately. There were no differences between the two routes of administration with respect to rates of hyperstimulation or neonatal asphyxia. There were more caesarean sections in the vaginal misoprostol group, but the difference was not statistically significant. CONCLUSIONS: Compared with oral misoprostol, vaginal misoprostol for induction of labour at term results in a shorter induction-to-delivery time, with fewer doses required per patient. Vaginal misoprostol may be associated with higher rates of caesarean section than oral misoprostol. PMID- 11213000 TI - A randomised controlled trial of epidural compared with non-epidural analgesia in labour. AB - OBJECTIVES: To investigate possible short and long term side effects of epidural analgesia, compared with non-epidural analgesia for pain relief in labour. DESIGN: Randomised controlled study, with long term follow up by questionnaire. Analysis by intention-to-treat. SETTING: Busy maternity unit within a district general hospital in England. PARTICIPANTS: Three hundred and sixty nine primigravid women in labour were included (randomised allocation: epidural n = 184, non-epidural n = 185). MAIN OUTCOME MEASURES: Backache at three and twelve months after delivery, instrumental delivery rates and maternal opinion of pain relief in labour. RESULTS: No significant differences were found in the reported incidence of backache between the groups at three months: middle backache [22% vs 20%, chi2 = 0.057, P = 0.81; odds ratio (95% CI) 1.4(0.9-2.3)]; low backache [35% vs 34%, chi2 = 0.009, P = 0.92; odds ratio (95% CI) 1.0(0.6-1.6)]. Nor were there significant differences at 12 months: [middle backache 16% vs 16%, chi2 = 0.013, P = 0.91; odds ratio (95% CI) 1.0(0.5-1.8)]; or low backache [35% vs 27%, chi2 = 1.91, P = 0.17; odds ratio (95% CI) 1.4(0.9-2.3)]. The incidence of instrumental delivery was somewhat higher in the epidural group [30% vs 19%, odds ratio (95% CI) 1.77(1.09-2.86)]. Maternal satisfaction was not significantly different between the groups. CONCLUSIONS: This study provided no evidence to support the suggestion of a direct association between the use of epidural anaesthesia in labour and the incidence of long term backache. Despite a significant proportion of women in each group not receiving their allocated analgesia, a significant difference in terms of instrumental delivery rates remained. Satisfaction in both groups of women was high. PMID- 11213001 TI - The long-acting progestogen-only contraceptive injections: an update. PMID- 11213002 TI - The Ipswich childbirth study: one year follow up of alternative methods used in perineal repair. AB - OBJECTIVE: To assess the long term implications of four alternative approaches to postpartum perineal repair. DESIGN: A stratified randomised controlled trial using a 2x2 factorial design. SETTING: Original recruitment at the Maternity Unit at Ipswich Hospital NHS Trust, a district general hospital, between 1992 and 1994. SAMPLE: Seven hundred and ninety three women who had participated in the Ipswich Childbirth Study--a trial among women who had required repair of episiotomy or first or second degree tears--at least one year previously. METHODS: Self-completed postal follow up at least one year after recruitment to trial comparing 1. two-stage repair leaving the skin unsutured with standard three-stage repair, and 2. polyglactin 910 with chromic catgut as suture material for the repair. MAIN OUTCOME MEASURES: Failure to resume pain-free intercourse; persistent perineal pain; perineum feeling different; resuturing; time to resume pain-free intercourse; and dyspareunia. RESULTS: Fewer women allocated two-stage repair reported that the perineum felt different (30% versus 40%; RR 0.75; 95% CI 0.61 to 0.91; 2P < 0.01); otherwise there were no clear differences between the two methods. Women allocated polyglactin 910 were less likely to have dyspareunia (8% versus 13%; RR 0.59, 95% CI 0.39 to 0.91; 2P = 0.02) and less likely to fail to resume pain-free intercourse (8% versus 14%; RR 0.57, 95% CI 0.38 to 0.87; 2P < 0.01). CONCLUSION: Two-stage repair of perineal trauma leaving the skin unsutured appears to reduce the likelihood of the perineum feeling different from before delivery, in addition to less pain and dyspareunia initially; there were no apparent disadvantages. Polyglactin 910 reduces dyspareunia long term, indicating that the short term benefits of this material over chromic catgut persist. PMID- 11213003 TI - Postpartum intrauterine pressure studies of the uterotonic effect of oral misoprostol and intramuscular syntometrine. AB - OBJECTIVES: To investigate the effect of oral misoprostol in dosages varying from 200 microg to 800 microg on postpartum uterine contractility and to establish their side effects. DESIGN: A prospective descriptive study. PARTICIPANTS: Fifty seven women who delivered vaginally after spontaneous labours not requiring augmentation. METHODS: Within 5 minutes of delivery of the placenta, a calibrated Gaeltec catheter with an intrauterine pressure transducer at its tip was inserted transcervically into the uterine cavity. Cumulative uterine activity was recorded for 30 minutes in each woman before administering the oral misoprostol tablets and continued for a further 90 minutes after its administration. Thus each woman acted as her own control regarding changes in uterine contractility. Uterine activity was recorded on a Sonicaid Meridian fetal monitor, which measures active contraction area automatically. The incidence of side effects was also recorded. RESULTS: There was no statistical difference (P = 0.887) in the adjusted mean difference in cumulative uterine activity following all the doses of oral misoprostol, compared with intramuscular syntometrine, the largest difference being seen in oral misoprostol 200 microg (adjusted mean difference -2282 kPas s, 95% CI -7954 to 3390 kPas s). The mean onset of action of oral misoprostol (6.1, SD 2.1 min) was significantly slower than that of intramuscular syntometrine (3.2, SD 1.5 min; P = 0.002), but their durations of action were similar (P = 0.637). In the misoprostol group the commonest side effects were shivering (36%) and a rise in body temperature above 38 degrees C (40%). In the syntometrine group, the most commonly observed side effect was moderate uterine pain (nine out of ten women) and a rise in diastolic blood pressure of 20 mmHg (two out of ten women). CONCLUSION: The results of this study show that oral misoprostol has a definite uterotonic effect on the postpartum uterus. At doses of 200 microg to 400 microg, oral misoprostol has a similar uterotonic effect to intramuscular syntometrine. Higher doses of oral misoprostol are associated with significantly more side effects. PMID- 11213004 TI - Trends in risk factors for caesarean sections in France between 1981 and 1995: lessons for reducing the rates in the future. AB - OBJECTIVE: To assess the effects of the characteristics of mothers, fetuses and maternity units on the trends in caesarean section use, especially for primiparae. DESIGN: Cross sectional surveys. SETTING: Maternity units. POPULATION: Two representative national samples of births including 5410 newborns in 1981 and 13318 in 1995. METHOD: Univariate analysis and logistic regression analysis. RESULTS: The overall rate of caesarean section rose from 10.7% in 1981 to 15.3% in 1995. This trend is mainly attributable to the increases in the proportion of previously sectioned women (from 4.1% to 8.2%) and in caesarean sections for primiparae (from 12.6% to 17.8%). Among primiparae several maternal risk factors such as late childbearing and obesity before pregnancy were more frequent in 1995 than in 1981. The increase in caesarean sections affected both the high risk group (25.4% to 32.4%) and the low risk group (8.1% to 12.0%). CONCLUSION: A significant reduction in the overall rate cannot be achieved without regulating caesarean section use for primiparae. Strategies to change delivery patterns should be aimed at both high and low risk women. PMID- 11213005 TI - Venous thromboembolism in pregnancy and the puerperium: incidence and additional risk factors from a London perinatal database. AB - OBJECTIVE: To determine the incidence of venous thromboembolism in pregnancy and the puerperium and to identify risk factors for pregnancy-related venous thromboembolism. DESIGN: Cohort study and case-control study. SETTING: London, UK. POPULATION: 395,335 women with live births or pregnancies of 24 or more weeks of gestation between 1988 and 1997. METHODS: Data extraction from the St Mary's Maternity Information System database. Random sample of 5% for case-control study. MAIN OUTCOME MEASURES: Incidence of venous thromboembolism; odds ratios for variables associated with venous thromboembolism. RESULTS: The incidence of venous thromboembolism was 85/100,000 maternities. There were approximately twice as many postpartum as antepartum events. Blood group A, multiple pregnancy, caesarean section, cardiac disease, delivery at gestational age of < 36 weeks, a body mass index of > or = 25, or more and maternal age of 35 or over were all found to increase incidence of venous thromboembolism. CONCLUSIONS: Although venous thromboembolism is the leading cause of maternal deaths in the UK, it is still a rare event. Most of these events are deep vein thromboses occurring in the postpartum period. Antenatally multiple birth is an important risk factor. Postnatally women who have had a caesarean section, premature delivery or history of cardiac disease should be assessed carefully for venous thromboembolism. PMID- 11213006 TI - Is maternal underweight really a risk factor for adverse pregnancy outcome? A population-based study in London. AB - OBJECTIVE: To determine the maternal and fetal risk of adverse outcome during pregnancy in relation to low maternal body mass index in an unselected population. DESIGN: Retrospective analysis. METHODS: Information for the years between 1988 and 1997 was extracted from a validated maternity database, including all but one of the maternity units in the North West Thames Region; 215,105 completed singleton pregnancies were studied. Comparison of pregnancy outcome was made on the basis of maternal body mass index at booking. There were 176,923 with a normal weight body mass index ( = 20 < 25). There were 38,182 with an underweight body mass index (< 20). Comparisons included antenatal complications (e.g. gestational diabetes, pre-eclampsia); intervention in labour, maternal morbidities (e.g. infection, postpartum haemorrhage, pulmonary thromboembolism); and neonatal outcome (admitted to special care baby unit at 24 hour of age, gestation at delivery, birthweight, stillbirth). Data are presented as percentages of outcomes in the normal and underweight groups with adjusted odds ratios and confidence intervals according to body mass index group. RESULTS: In the underweight group only antenatal anaemia, preterm delivery and birthweight below the 5th centile were more frequent than in women of normal body mass index. The prevalence of certain complications, including development of gestational diabetes mellitus, pre-eclampsia, obstetric intervention and postpartum haemorrhage, were significantly lower in those with low body mass index. CONCLUSION: Low maternal body mass index is associated with increased prevalence of some pregnancy complications, notably preterm delivery and low birthweight, but overall the outcome is favourable and several adverse outcomes are less common in this group of women. PMID- 11213007 TI - Effects at age nine of maternal smoking in pregnancy: experimental and observational findings. AB - OBJECTIVES: To compare long term outcomes of a randomised controlled trial of anti-smoking education in pregnancy and to examine the same outcomes according to maternal pregnancy smoking behaviour. DESIGN: Follow up of the population included in the randomised controlled trial nine years later and of ex-smokers and non-smokers within the same hospital population. SETTING: A maternity hospital in Birmingham with follow up of children in schools and mothers at home. POPULATION: 1218 smokers recruited to the trial; also 191 ex-smokers at booking and 414 non-smokers throughout pregnancy. METHODS: Children were assessed individually by psychologists in schools, and mothers interviewed at home to obtain additional information relevant to cognitive development and growth. Information on smoking during pregnancy was obtained from mothers and obstetric data from computerised case-notes, both recorded immediately following delivery. MAIN OUTCOME MEASURES: Height, weight, IQ and neurological soft signs at 9.4 years. RESULTS: Differences in birthweight and length between the intervention and control groups were confirmed but no intervention-control differences were found at age 9.4 for weight, height, IQ or neurological soft signs. Differences were found for height and IQ according to mothers pregnancy smoking behaviour, but smoking did not remain an independent predictor after taking account of confounding factors. Alternative classifications of smoking behaviour, taking account of the gestation at stopping and mean cigarette consumption throughout pregnancy likewise showed no effect. CONCLUSIONS: The well established early hazards of smoking during pregnancy seem to be resolved by later childhood, with no evidence of direct long term effects on growth or cognitive functioning. PMID- 11213008 TI - The effectiveness of the levonorgestrel-releasing intrauterine system in menorrhagia: a systematic review. AB - OBJECTIVE: To determine whether the levonorgestrel-releasing intrauterine device (LNG-IUS), licensed at present for contraceptive use, may reduce menstrual blood loss with few side effects. If effective, surgery could be avoided with consequent resource savings. METHODS: A systematic review addressing the effectiveness and cost effectiveness of the LNG-IUS for menorrhagia was undertaken. RESULTS: Five controlled trials and five case series were found which measured menstrual blood loss. Nine studies recorded statistically significant average menstrual blood loss reductions with LNG-IUS (range 74%-97%). Another showed reduction in menstrual disturbance score. The LNG-IUS was more effective than tranexamic acid, but slightly less effective than endometrial resection at reducing menstrual blood loss. In one study, 64% of women cancelled surgery at six months, compared with 14% of control group women. In another, 82% were taken off surgical waiting lists at one year. No cost effectiveness studies were found. DISCUSSION: Small studies of moderate quality indicate the LNG-IUS is an effective treatment for menorrhagia. Costs may be less than for tranexamic acid in primary and secondary care. Although its use may reduce surgical waiting lists, cost effectiveness assessment requires longer follow up. CONCLUSION: Effectiveness and cost effectiveness relative to other treatments and the effect on surgical waiting lists can only be established in larger trials measuring patient-centred outcomes in women with menorrhagia. PMID- 11213009 TI - The effect of an intrauterine application of two percent lignocaine gel on pain perception during Vabra endometrial sampling: a randomised double-blind, placebo controlled trial. AB - OBJECTIVE: To determine whether two percent lignocaine gel can reduce the perception of pain during Vabra endometrial aspiration. DESIGN: Randomised, double-blind placebo-controlled trial. SETTING: Women's Health Directorate, Warrington Hospital NHS Trust. POPULATION: Women were referred to the endometrial sampling clinic for the investigation of pre and postmenopausal vaginal bleeding. METHODS: Randomisation to either pre-sampling intrauterine two percent lignocaine gel or an inert gel. Patients, recruiters and assessors were blinded to the gel used. MAIN OUTCOME MEASURES: The difference between the study groups in the proportion of women who, after Vabra sampling, recorded a pain score of > or = 6 out of 10 on a visual analogue scale. RESULTS: Three hundred and eight women were randomised, 284 (92%) completed a pain scale before and immediately after the procedure. After the procedure, 84 women (30%) recorded a pain score of > or = 6, 38 (26%) received anaesthetic and 46 (33%) an inert gel. The difference in the proportion of women recording a pain score of 6 or above between the two study groups was not significant (relative risk (RR) for the anaesthetic gel = 0.79 95% CI, 0.55, 1.14). CONCLUSIONS: Intrauterine application of 2% lignocaine gel did not significantly reduce the frequency with which women experienced unacceptable levels of pain or anxiety during endometrial aspiration compared with placebo. PMID- 11213010 TI - Randomised, double-blind, placebo-controlled trial of corticosteroids for the treatment of hyperemesis gravidarum. AB - OBJECTIVE: To assess the efficacy of corticosteroids in the treatment of severe hyperemesis gravidarum refractory to conventional management. DESIGN: Multicentre, double-blind, randomised, placebo-controlled trial. SETTING: Inpatient gynaecology wards in eight collaborating centres. POPULATION: Twenty five women with severe hyperemesis of which 24 completed the one- week study period. METHODS: Twenty-five women were randomised to receive either 40 mg prednisolone daily in two divided oral doses, or equivalent placebo tablets. If, after three days, a woman was still vomiting, medication was changed to the equivalent intravenous alternative (hydrocortisone 100 mg twice daily or normal saline injections) MAIN OUTCOME MEASURES: Frequency of vomiting and the dependence on intravenous fluid replacement therapy after one week of treatment. RESULTS: There was a non-significant trend towards improved nausea and vomiting and reduced dependence on intravenous fluids. However, steroid therapy led to an improved sense of wellbeing (P = 0.021), improved appetite (P = 0.039) and increased weight gain (P = 0.025) compared with placebo. There was no difference in pregnancy outcome between the treatment and placebo groups. CONCLUSIONS: This study supports a beneficial role for steroids in severe hyperemesis, but did not validate the hypothesis that they lead to rapid and complete remission of symptoms. The study was not large enough to demonstrate a significant improvement in the primary outcome measures. PMID- 11213011 TI - Excision of mature teratoma using culdotomy, with and without laparoscopy: a prospective randomised trial. AB - OBJECTIVE: To compare the results of removing mature teratoma with laparoscopy or without laparoscopy. DESIGN: A prospective, randomised trial. SETTING: Medical centre. PARTICIPANTS: Seventy-nine women with mature teratomas identified using results of ultrasound examinations and biochemical markers. INTERVENTION: Cystectomy with laparoscopic approach or without laparoscopic approach through a culdotomy. METHODS: Patients were randomly assigned to have their cysts removed via vaginal cystectomy without laparoscopy (n = 37, Group A) or laparoscopic cystectomy via culdotomy opening (n = 42, Group B). Inclusion criteria were history of vaginal delivery, no previous abdominal surgery, no history of pelvic inflammatory disease, no medical illness, and no presenting symptoms. Eight women randomised to Group A withdrew before surgery. The laparoscopically resected tumours were each put into a cellulose bag, and tumours without laparoscopic assistance were removed directly via the vagina. RESULTS: Blood loss in Group A (88 +/- 37 ml) was significantly more than that in Group B (64 +/- 20 ml, P = 0.000). The post-operative recovery times were 20 and 17 hours, respectively (P = 0.030). The rates of successful surgery were 58.6 and 97.6%, respectively (P = 0.002). The spillage rates were 44.8% and 19.0%, respectively (P = 0.006). There were no significant differences in tumour size, patient age, and operative time between groups. CONCLUSION: Cystectomy without assistance of laparoscopy could be applied to manage mature teratoma of the ovary; however, because of the difficulty of this technique, we had high percentages of tumour spillage and more blood loss during operation and a high percentage of patients who required conversion to laparotomy compared with laparoscopic cystectomy. We favoured laparoscopically assisted cystectomy to manage mature teratoma. PMID- 11213012 TI - Oestrogen deficiency causes DNA damage in uterine leiomyoma cells: a possible mechanism for shrinkage of fibroids by GnRH agonists. AB - OBJECTIVE: To examine whether gonadotrophin-releasing hormone agonist or oestradiol can directly affect DNA in leiomyoma cells. DESIGN: In vitro explant culture of leiomyoma cells. SETTING: University research group. SAMPLE: Leiomyoma cells were cultured from the specimens of four premenopausal women at myomectomy. METHODS: The presence of gonadotrophin-releasing hormone receptor in leiomyoma cells was determined by reverse transcriptase-olymerase chain reaction. Leiomyoma cells were treated with gonadotrophin-releasing hormone agonist or cultured in different concentrations of oestrogen, progesterone or fetal calf serum for one, four or seven days. MAIN OUTCOME MEASURES: Cell number, expression of proliferating cell nuclear antigen, and DNA damage after one, four or seven days of treatment. RESULTS: Gonadotrophin-releasing hormone receptor messenger ribonucleic acid was detected on cultured leiomyoma cells. Leiomyoma cell growth was not affected by the addition of gonadotrophin-releasing hormone agonist or progesterone, but increased with oestrogen or fetal calf serum supplementation. Overexpression of proliferating cell nuclear antigen was prevented in cultures added with oestrogen or fetal calf serum, but not related to gonadotrophin releasing hormone agonist treatment. Significant decreases in DNA damage as indicated by decreased comet number were found in the leiomyoma cultures treated with oestrogen or fetal calf serum for four and seven days but not with gonadotrophin-releasing hormone agonist or progesterone. Furthermore, 5% fetal calf serum supplementation was more growth supporting and more significantly reduced the comet number than 250 pM 17 beta-oestradiol. CONCLUSION: Cell growth, proliferating cell nuclear antigen expression and DNA damage are dependent on oestrogen or fetal calf serum, but independent of gonadotrophin-releasing hormone agonist or progesterone. Our findings suggest that gonadotrophin-releasing hormone agonist-induced leiomyoma shrinkage may be due in part to a mechanism involving DNA damage, and support the hypothesis that gonadotrophin-releasing hormone agonist exerts its action indirectly through oestrogen action on the tumour level. PMID- 11213013 TI - Involvement of specific chromosomes in radiation-induced rearrangements detected by fluorescence in situ hybridization (FISH). AB - We investigated the involvement of chromosomes in dicentrics and translocations in human peripheral blood lymphocytes exposed to X-rays in vitro. Chromosomes 2, 4, 8, 13, 15, 16, and 22 were analyzed in three cocktails of different combinations using whole chromosome probes (WCP) with the fluorescence in situ hybridization (FISH)-painting technique. The results showed overexpression of chromosomes 2, 8, and 22 in translocation, the majority being of the complete type. Chromosome 4 was underrepresented in translocation formation in both combinations, that is, 2 + 4 + 8 in cocktail I and 4 + 13 + 22 in cocktail II. Its participation in dicentric production was in good agreement with its DNA content in association with 2, 4, and 8, whereas it was underexpressed in the combination of 4 + 13 + 22. DNA-proportional involvement was noticed with chromosomes 13 and 16 in all exchange aberrations. Underexpression of chromosome 15 was observed in translocation, which is contradictory to its overexpression in dicentric formation. The participation of chromosome 22 was predominant for both translocations and dicentrics, compared with its DNA content. The overall observation of our study supports the assumption of DNA-proportional distribution of Lucas et al. However, more data are required for chromosomes 4, 8, 15, and 22 in combination with other chromosomes. PMID- 11213014 TI - Role of antioxidant enzymes in radiosensitivity of human blood cells. AB - The marked variability in radiation response among individuals of the same age group prompted us to investigate the role of antioxidative enzyme activity. Micronuclei (MN) and enzyme assays were performed on blood samples of healthy male volunteers. The procedure consisted of micronucleus analysis and measurement of the superoxide dismutase (SOD) activity in harvested blood samples irradiated in vitro with 2 Gy gamma-rays and in unirradiated control samples for each individual. We found that the yield of radiation-induced micronuclei was in the range of 112 to 378 micronuclei per 1000 binucleated cells. The activity of cytosol superoxide dismutase (CuZnSOD) was reduced, whereas the activity of manganese superoxide dismutase (MnSOD) was markedly elevated in the blood samples harvested in lymphocyte cultures after irradiation. The analysis of our results showed that MnSOD plays the most important role in radiation-induced cellular damage. The results of this investigation showed that measurement of micronuclei and the activities of SOD in harvested human blood cells can serve as a rapid predictive assay of radiosensitivity in a clinical setting. PMID- 11213015 TI - Nontoxic, mutagenic, and clastogenic activities of Mate-Chimarrao (Ilex paraguariensis). AB - Aqueous extracts of Ilex paraguarariensis (mate-chimarrao), a species that belongs to the Aquifoliaceae family, were analyzed for the presence of genotoxic, mutagenic, and clastogenic activities through bacterial trials based on the induction of the SOS functions, as well as in human lymphocytes in vitro and in mammalian cells in vivo. The extracts of mate-chimarrao were genotoxic, as assessed by lysogenic induction in Escherichia coli, and they also induced mutagenesis in Salmonella typhimurium. They addition of S9 microsomal fraction, catalase, thiourea, or dipyridyl counteracted the genotoxic activity of mate chimarrao, suggesting that oxygen reactive species play an essential role in the genotoxicity of mate-chimarrao extracts. The extracts were not clastogenic in vivo (bone marrow cells of rats) in our experimental conditions, but we have observed an increased frequency of chromosomal aberrations in mate-chimarrao treated human peripheral lymphocytes. Our results suggest that a high consumption of mate-chimarrao can potentiate carcinogenesis in the human oropharynx and esophagus. PMID- 11213016 TI - Cytogenetic toxicity of vincristine. AB - The anticancer drugs vincristine sulphate (VCR) and cyclophosphamide (CTX) were tested for their cytogenetic effects in the bone marrow cells of Swiss mice. The end points investigated were chromosomal aberrations and mitotic index at 24 hours posttreatment and micronuclei (MN) at 30 hours posttreatment in bone marrow cells of male and female mice after a single intraperitoneal exposure. The doses tested were VCR 0.25, 0.5, and 1.0 mg/kg and CTX 40 mg/kg b.w. of mice. Significant percentages of chromosomal aberrations and significant numbers of micronuclei per thousand polychromatic erythrocytes (PCEs) that were induced were recorded from bone marrow of each of the VCR-treated groups of mice. There were no significant differences between the percentages of dividing cells in the VCR treated group and the vehicle control groups of mice. Peculiarly, in the chromosomal aberration study, the male mice were found to be more responsive to VCR than the females, and the aberrations per hundred metaphases were found to be decreased when the dose of VCR was increased. The percentage of dividing cells was also higher with the lowest dose of VCR tested. However, there was a dose dependent, but nonlinear, increase in MN per thousand PCEs. The results were compared with the already available fragmentary and self-contradictory data on the genotoxicity of VCR in mice and in other mammalian test systems. PMID- 11213017 TI - Toxicity of aflatoxin: effects on spermatozoa, oocytes, and in vitro fertilization. AB - Aflatoxin B1 has been reported to have a deleterious effect on the reproductive capacity of laboratory and domestic animals. We wanted to elucidate the mechanistic aspect of this phenomenon by determining the toxic potential of aflatoxin B1 on the in vitro fertilizing ability of oocytes and epididymal sperm in albino rats. In vitro fertilization medium (IVFM) containing aflatoxin B1 at concentrations of 2.0, 4.0, 8.0, and 16.0 ppb was cultured with oocytes obtained from superovulated healthy fertile female rats and exposed to sperm cells. Epididymal sperm capacitated in IVFM, with or without aflatoxin B1, were exposed to oocytes, and the rates of fertilization in the two experiments were assessed. Aflatoxin B1 significantly reduced the mean number of ova fertilized, even at the lowest concentration. Exposure to aflatoxin caused a significant reduction in the motility of sperm cells. These results demonstrate the adverse effects of aflatoxin B1 on oocytes, spermatozoa, and in vitro fertilization. PMID- 11213018 TI - Morphometric analysis of rat testis following chronic exposure to cigarette smoke. AB - PURPOSE: To assess the effect of chronic exposure to cigarette smoke on spermatogenesis in Sprague-Dawley rats. MATERIALS AND METHODS: Twenty 5-day-old Sprague-Dawley rats were exposed daily to cigarette smoke by the Walton smoking machine for a period of 15, 30, and 45 days. Age-matched Sprague-Dawley rats exposed to room air with the smoking machine served as controls. Rats were sacrificed from each group at 15, 30, and 45 days and the testes were removed. Fifty seminiferous tubules were assessed in each group. Morphometric and histopathologic analyses of the testes were carried out. The following parameters were studied: (1) Number of germ cells (step 7 spermatids), (2) seminiferous tubule diameter, (3) height of germinal epithelium, (4) presence of degenerating or sloughed cells, (5) failure of release of spermatids into the tubular lumen, and (6) degeneration of Leydig cells. Statistical analysis was performed using ANOVA followed by the t test. RESULTS: There was a significant decrease in the germ cell count (step 7 spermatids) in the rats exposed to cigarette smoke for 30 days (93.19 versus 98.15 step 7 spermatids in the control animals (p < 0.001). This decrease persisted in the rats exposed to cigarette smoke for 45 days (82.47 versus 103.01 step 7 spermatids in control animals, p < 0.001). The mean seminiferous tubule diameter was significantly reduced only in the rats exposed to cigarette smoke for 45 days (0.283 microm versus 0.299 microm in the control animals, p < 0.001). There was no significant difference in the height of the germinal epithelium, and no degenerating cells were noted in either group. CONCLUSIONS: Cigarette smoke adversely affects spermatogenesis in pubertal Sprague-Dawley rats. PMID- 11213019 TI - Chronic cigarette smoking induces an oxidantantioxidant imbalance in the testis. AB - OBJECTIVES: We have previously demonstrated the harmful effect of chronic inhalation of cigarette smoke on the testis in Sprague-Dawley rats. The aim of the present study was to investigate the role of free oxygen radicals and reactive oxygen species in inducing testicular damage in Sprague-Dawley rats following exposure to cigarette smoke. MATERIALS AND METHODS: Sprague-Dawley rats, 25 days old, were exposed daily to cigarette smoke by the Walton smoking machine for a period of 15, 30, and 45 days. Age-matched Sprague-Dawley rats were exposed to room air with the smoking machine and served as controls. Rats were sacrificed from each group at 15, 30, and 45 days and the testes were removed. The testicular tissue levels of glutathione and lipid peroxidation product malonaldehyde (MDA) were measured colorimetrically using the Bioxytech GSH-400 and LPO-586 kits, respectively. The activity of glutathione peroxidase was assessed colorimetrically using the Bioxytech GPx-340 kit. Statistical analysis was performed using ANOVA followed by the t test. RESULTS: There was a 47.8% increase in the MDA in the treated rat testis compared with the control rat after 45 days of exposure to cigarette smoke or air, respectively (p < 0.05). This was associated with a parallel significant decrease in the level of glutathione and glutathione peroxidase activity in the treated rat testis, 38.2% and 29.1%, respectively, after 45 days of cigarette smoke exposure (p < 0.05). No significant difference was noted in the levels of glutathione, glutathione peroxidase, and lipid peroxidation end products after 15 and 30 days of treatment. CONCLUSIONS: Chronic cigarette smoke inhalation is associated with an increase in the level of oxidants and a simultaneous decrease in the level of antioxidants in the rat testis. This abnormality of the oxidant-antioxidant balance may be one of the mechanisms leading to testicular tissue damage and abnormal spermatogenesis in the rat testis following chronic inhalation of cigarette smoke. PMID- 11213020 TI - Potentiation of docetaxel antitumor activity by batimastat against mouse forestomach carcinoma. AB - Docetaxel is a chemical compound belonging to the taxoid class of anticancer agents. Batimastat (BB-94) is the first matrix metalloproteinase inhibitor entering clinical trials. To improve the treatment of tumors, we studied the combined effects of docetaxel and batimastat on mouse forestomach carcinoma (MFC), and compared them with doxorubicin. In vitro growth curve analysis, MTT assay, and clonogenic assay were used to determine the cytotoxic effect of docetaxel or/and BB-94 on MFC. They showed that docetaxel, but not BB-94, had a significant cytotoxicity and that the effect of docetaxel was not enhanced by BB 94. In an early stage MFC tumor model, an obvious antitumor effect of docetaxel or doxorubicin given iv at maximum tolerated dose (MTD) was observed. Tumor growth inhibition was greater for docetaxel + BB-94 (96.0%) than for doxorubicin + BB-94 (88.0%), docetaxel (89.0%), doxorubicin (68.0%), and BB-94 (33.0%). Docetaxel showed activity against advanced stage MFC tumor in a dose-dependent manner and was more effective at MTD than doxorubicin, with 4/5 regression, 46.5 days tumor growth delay, and 2.8 log10 tumor-cell kill. Our results suggest that docetaxel is an effective new cytotoxic drug against MFC tumor and that BB-94 enhances the antitumor activity of docetaxel in the dose and schedule used. PMID- 11213021 TI - Effects of nitric oxide donors on energy metabolism of rat erythrocytes. AB - It is known that nitric oxide (NO) influences the activities of glycolytic enzymes, resulting in alteration of glycolysis rate. We investigated the effect of NO donors on the energy metabolism of rat erythrocytes. Rat erythrocyterich blood suspensions were aerobically incubated for 2 hours (1) as controls or (2) with different concentrations of NO donors: nitroglycerin (NTG), isosorbide dinitrate (ISDN), molsidomine (MO), and sodium nitroprusside (SNP). NTG, ISDN, MO, and SNP significantly (p < 0.05) increased glucose consumption and lactate accumulation in rat erythrocytes in a dose-dependent manner, indicating stimulation of glycolysis. The increased rate of glycolysis was accompanied by elevation of energy production (p < 0.05), but no changes in ATP levels were observed. The dose-dependent increase of glycolytic ATP production and the unaltered levels of ATP resulted in considerably shortened ATP-turnover time with the maximal experimental doses of NO donors used, indicating the stimulation of the ATP-consuming process in rat erythrocytes. The metabolic effects of NTG, ISDN, MO, and SNP were not mimicked by exogenous 8-Br-cGMP, NaNO2, or NaNO3, suggesting that the NO donor-induced stimulation of glycolysis and abbreviation of ATP-turnover time in rat erythrocytes was mediated by NO as an effector molecule, irrespective of the irreversible scavenger effect of hemoglobin. The implications of the NO effect on energy metabolism of erythrocytes is discussed. PMID- 11213022 TI - In vivo experimental model for silicosis. AB - The selection of an experimental model for silicosis requires a thorough understanding of many pulmonary parameters specific to the experimental animal (e.g., clearance time, penetration curves, anatomical differences), as well as the strain's sensitivity to different conditions. The pulmonary response of three rat strains (i.e., Fischer 344, Sprague-Dawley, and Wistar) to silica dust was compared using two methods of exposure: intratracheal injection and inhalation. The test period lasted 3 months for injection and 6 and 12 months for inhalation. The histological study of the lung revealed a distinct nodular reaction in Sprague-Dawley and Wistar strains. Intratracheal injections led to the development of fibrotic nodules in Wistar rats, whereas such silicotic nodules were infrequent in injected Fischer 344 rats, and almost absent when exposure was by inhalation. Sprague-Dawley and Fischer 344 rats showed frequent thickening and metaplasia of the alveolar walls near the terminal bronchioles. This tendency was particularly pronounced in rats exposed by inhalation (especially Fischer 344 rats). Macroscopic examination (wet lung weight) and biochemical dosing (lung silica, hydroxyproline, and lipid content) revealed an increase in the various parameters examined in Sprague-Dawley rats relative to the other two strains, regardless of the type of exposure. The histological examination, however, leads us to conclude that the Wistar rats offer the best experimental model for silicosis, because their pulmonary reaction is more characteristic of the human condition than that of the other two strains. PMID- 11213023 TI - Antimutagenesis studies of magnesium and calcium salts. AB - Magnesium is a microelement that is essential for biological functions and particularly for cellular metabolism. It has a central role in protein, lipid, carbohydrate, and nucleic acid synthesis, and it is important for muscular physiology and nerve excitability. Magnesium has an important role in the stability of biological membranes, it controls immune phenomena, and it activates over 300 enzymes. However, the mechanism of action of magnesium salts has not been well investigated and, in particular, its antimutagenesis properties and its effects in the detoxification of free radicals need further study. We investigated the effect of magnesium chloride, sulphate, carbonate, and oxide on the yeast Saccharomyces cerevisiae D7 strain, to evaluate their ability to protect against genotoxic damage. We found that magnesium salts induced antimutagenic effects in the cells harvested in the logarithmic phase by decreasing the induction of hydrogen peroxide. This, however, did not occur in the stationary phase. We also studied calcium salts of the type corresponding to those of magnesium and their protective role against the oxidative damage of free radicals and enzymatic activities, such as catalase, glutathione peroxidase, and superoxide dismutase, which are involved in antioxidative defenses. PMID- 11213025 TI - The effects of short-term blood pressure variability and nighttime blood pressure levels on cognitive function. AB - We investigated the relationship between 24-h blood pressure (BP) and cognitive function. We performed the Hasegawa Dementia Scale Revised (HDSR), the Mini Mental State Examination (MMSE), and the Raven's Coloured Progressive Matrices Test (RCPM) in 88 subjects (71+/-9 years) with no history of stroke. Ambulatory BP was non-invasively measured using a TM2421 for 24 h in all patients. Whereas 90% of the scores converged into a narrow range between 25 and 30 points in the HDSR and the MMSE tests, the RCPM score was widely distributed, ranging from 9 to 36 points. The subjects were therefore divided into three groups of > or =25, 26 30, and 31-36 according to their RCPM scores. Subjects with lower scores were significantly associated with increased short-term BP variability during the daytime (p<0.05) and had a tendency toward higher nighttime SBP (p=0.05) compared with those with higher scores. Increased short-term variability of daytime BP and high nighttime systolic BP were associated with cognitive impairment as assessed by the RCPM. The RCPM, which can assess the capacity for judgment through visual information processing, may detect earlier stages of cognitive impairment related to high BP. To prevent a deterioration of cognitive function, strict control of nighttime BP and suppression of short-term BP variability are thus necessary. PMID- 11213024 TI - Clinical usefulness of duplex ultrasonography for the assessment of renal arteriosclerosis in essential hypertensive patients. AB - The present study was carried out to investigate whether the renal resistive index (RRI), obtained by ultrasonic duplex scanning, is useful for the evaluation of renal arteriosclerosis in essential hypertensive patients. We also studied the relationships between RRI and other kinds of hypertensive target-organ damage, including carotid atherosclerosis. One hundred and two patients (56.4+/-9.4 years) with untreated mild or moderate essential hypertension were examined. The normal range of RRI was determined for 12 normal age-matched volunteers (55.0+/ 6.6 years). Hypertensive organ damage was evaluated by funduscopy, electrocardiograms, and carotid B-mode imaging. Based on the mean and distribution of RRI in normal volunteers (0.60+/-0.05), the normal upper limit of RRI was found to be 0.7. RRI was correlated with creatinine clearance (CCr) (r= 0.61, p<0.05), and blood urea nitrogen (r=0.46, p<0.05), but not with serum creatinine. In addition, the incidence of abnormal RRI (>0.7) was higher in patients with left ventricular hypertrophy and in those with advanced carotid atherosclerosis (p<0.01, respectively). Thus, RRI appears to be more strongly associated with CCr than with serum creatinine, and it increases in patients with hypertensive end-organ damage. The assessment of RRI may be useful for the evaluation of early renal damage in essential hypertension. PMID- 11213026 TI - Influence of night shift work on psychologic state and cardiovascular and neuroendocrine responses in healthy nurses. AB - Night shift work has often been associated with increasing degree and frequency of various psychologic complaints. The study examined whether psychologic states after night work are related to adaptive alterations of the cardiovascular and neuroendocrine systems. We studied 18 healthy nurses (age 29+/-2 years) engaged in a modified rapid shift rotation system (day work, 8:15-17:15; evening work, 16:00-22:00; night work, 21:30-8:30). Blood pressure, heart rate, RR interval variability (L/H and HF power spectrum for sympathetic and vagal activities), and physical activity were measured using a multibiomedical recorder for 24 h from the start of work during the night and day shifts. Plasma ACTH and cortisol concentrations were measured at the end of each shift and at 8:30 AM on a day of rest. Each subject's psychologic state was assessed using a validated questionnaire. Among the parameters measured, scores for confusion, depression, anger-hostility, fatigue and tension-anxiety were highest, and scores for vigor lowest, after a night shift. Systolic blood pressure and heart rate during work were lower during night shift than during day shift (119+/-2 vs. 123+/-1 mmHg, p<0.05 and 75+/-1 vs. 84+/-2 bpm, p<0.001, respectively). Both parameters were lower still (p<0.005 and p<0.05) when measured outside of the hospital under waking conditions following a night shift than following a day shift, even though the levels of physical activity were similar. The HF power spectrum of RR interval variability was greater not only during work (24.2+/-2.1 vs. 18.5+/-1.8 ms, p<0.005) but also during the awake period (29.1+/-2.5 vs. 24.4+/-2.6 ms, p<0.005) after the night shift compared with the day shift. Plasma ACTH and cortisol concentrations were lower after night work than in the day of rest (7.3+/-1.2 vs. 11.5+/-2.3 pg/ml, p<0.1 and 11.1+/-1.1 vs. 14.4+/-1.1 mg/dl, p< 0.05). Systolic and diastolic blood pressures during night shift work and the subsequent awake period correlated positively with scores for vigor and negatively with scores for confusion (p<0.05). Plasma ACTH and cortisol concentrations did not correlate with any psychologic scores. We conclude that psychologic disturbances after night work were associated with altered cardiovascular and endocrine responses in healthy nurses. Some of the psychologic complaints may be attributable to lower waking blood pressure. PMID- 11213027 TI - Risk factors and predictors of coronary arterial lesions in Japanese hypertensive patients. AB - The morbidity rate of coronary artery disease has recently increased in Japan. This is attributable to changes from traditional to more westernized lifestyles. In this study, we therefore examined the risk factors and predictors of coronary arterial lesions in Japanese patients with essential hypertension. Coronary angiography was performed in 109 consecutive essential hypertension patients (57 men and 52 women; 66 +/- 8.0 years of age) with either angina pectoris or atypical chest pain, who were chosen from 485 consecutive hypertensive patients in a hypertension clinic in Sendai, Japan. Coronary arterial stenosis of greater than 50% was defined as significant and used as a dependent variable for the multiple regression analysis. Risk factors were defined as factors confirmed to have a causal relationship with coronary arterial lesions, whereas arteriosclerotic complications and hypertensive target organ damage were defined as predictors. Multiple logistic regression analysis was performed using these parameters as independent variables. Of 109 patients, 25 had a coronary arterial stenosis greater than 50%. A smoking habit (odds ratio (OR): 4.48; 95% confidence interval (CI): 1.13-17.82; p<0.05), hypercholesterolemia (OR: 5.34; 95% CI: 1.52 18.73; p<0.05), and 24-h diastolic blood pressure (OR: 2.33; 95% CI: 1.06-5.16; p<0.05) were significant risk factors, whereas carotid intima-media thickness (OR: 5.85; 95% CI: 1.48-23.2; p<0.05) was a significant predictor of coronary arterial lesion. When two of the major risk factors (a smoking habit, hypercholesterolemia, or impaired glucose tolerance including diabetes mellitus) were clustered in addition to the hypertension, the risk of coronary arterial lesions increased by 6.7 to 10.1 times. These findings indicate that the major risk factors established in Caucasians, i.e., a smoking habit, hypercholesterolemia and blood pressure level, are also risk factors for coronary arterial lesions in Japanese with essential hypertension. The presence of two or more risk factors increases the risk of coronary arterial lesions synergistically in the presence of hypertension. PMID- 11213028 TI - 11beta-hydroxysteroid dehydrogenase activity in human aortic smooth muscle cells. AB - 11beta-Hydroxysteroid dehydrogenases (11beta-HSD) interconvert cortisol, the physiological glucocorticoid, and its inactive metabolite cortisone in humans. There are two isoforms. The type 1 isoform (11beta-HSD1) catalyzes both 11beta dehydrogenation (cortisol to cortisone) and the reverse oxoreduction (cortisone to cortisol), but the type 2 isoform (11beta-HSD2) catalyzes only 11beta dehydrogenation. The diminished dehydrogenase activity has been demonstrated in resistance vessels of genetically hypertensive rats. However, the isoform(s) that plays a significant role in conferring the dehydrogenase activity on vasculature has not been determined. We investigated 11beta-HSD activities in human vascular smooth muscle cells by manipulating 11beta-HSD expressions with antisense oligonucleotides. The results showed that 11beta-HSD2 dominates functioning in the dehydrogenase mode in these cells. This indicates that impairment of 11beta HSD2 activity in vascular wall may be related to the pathogenesis of hypertension. PMID- 11213029 TI - Role of the central nervous system in the development of hypertension produced by chronic nitric oxide blockade in rats. AB - We examined the role of the central nervous system, and particularly the renin angiotensin (RA) system, in the development of hypertension produced by chronic inhibition of NO synthesis. In experiment 1, Wistar rats drank either nitro-L arginine-methyl ester (L-NAME) or tap water. Before L-NAME treatment rats were divided into 6 groups. Four of them were administered either losartan or artificial cerebroventricular fluid (a-CSF) intracerebroventricularly (i.c.v.) for 1 week using an osmotic mini pump. The other two groups were administered the same amount of losartan intravenously (i.v.). In experiment 2, cardiovascular responses to acute i.c.v. losartan and muscimol, a GABA(A) agonist, were examined in conscious L-NAME-treated rats. Finally, in experiment 3, effects of ablation of the AV3V (anteroventral third ventricle) area, known to be one of the centers of cardiovascular control, were tested in the development of L-NAME hypertension. The development of hypertension by L-NAME treatment was attenuated with chronic i.c.v. losartan in a dose-dependent manner, while i.v. losartan had no effect. One week after cessation of i.c.v. losartan, blood pressure was elevated to the same level as in a-CSF-infused, L-NAME-treated rats. Acute i.c.v. losartan produced no cardiovascular changes in either L-NAME-treated or control rats. On the other hand, although i.c.v. muscimol elicited depressor effects in both groups, these responses were significantly larger in L-NAME-treated rats. Cardiovascular responses to i.v. hexamethonium were similar in both groups. The existence of prior lesions in the AV3V area significantly attenuated the development of L-NAME-induced hypertension. These results indicate that the central RA system plays an important role in the development of hypertension produced by chronic inhibition of NO synthase. Moreover, disorder of the central GABA system, rather than that of the RA system, might be important in the maintenance of hypertension in this model. PMID- 11213030 TI - Hypothermia on NO-mediated neurogenic relaxation and on hypoxic inhibition in the response of canine cerebral arteries. AB - Cerebral arteries are innervated by nitric oxide (NO)-mediated vasodilator nerves, and hypoxia has been shown to attenuate neurogenic vasorelaxation. The present study examines the effects of hypothermia on neurogenic vasorelaxation and on the hypoxia-induced inhibition of the neurogenic vasorelaxation response. In isolated canine cerebral arteries, relaxant responses to transmural electrical stimulation (5 Hz for 40 s), mediated via NO synthesized from L-arginine, were not influenced by lowering the bathing media temperature from 37 degrees C to 30 degrees C but were attenuated at 25 degrees C. On the other hand, relaxations caused by nicotine and exogenous NO were not significantly attenuated but were prolonged by cooling to 25 degrees C. The responses associated with nerve stimulation by electrical pulses or nicotine were depressed by hypoxia (from about 500 mmHg of partial O2 pressure to about 45 mmHg) under normothermia. However, hypothermia at 25 degrees C prevented the inhibition by hypoxia of the neurogenic relaxation. It is concluded that the hypothermia-induced inhibition in the response to electrical nerve stimulation is not associated with a decreased synthesis and release of NO in vasodilator nerves nor with a reduced ability of smooth muscle to relax in response to NO. Interference with the propagation of action potentials might be involved in the inhibition via a fall of temperature. The fact that the hypoxia-induced impairment of vasodilator nerve function was prevented by cooling may partially explain the efficacy of hypothermia in protecting against ischemic neuronal injury in the brain. PMID- 11213031 TI - Effects of TCV-116 on endothelin-1 and PDGF A-chain expression in angiotensin II induced hypertensive rats. AB - Angiotensin II (Ang II) has been shown to stimulate cardiac growth and collagen synthesis in cultured vascular smooth muscle cells and to increase fibroblast proliferation. Chronic infusion with Ang II increases blood pressure and activates growth mechanisms to produce hypertrophy of the heart. This study investigated the effects of an Ang II type 1 receptor antagonist, TCV-116, on preproendothelin-1 (preproET-1), ETA receptor and platelet-derived growth factor (PDGF) A-chain expression in the left ventricle of Wistar-Kyoto rats treated for 2 weeks with Ang II (200 ng x kg(-1) x min(-1)), and the relation of these effects to myocardial remodeling. Rats given Ang II alone (ANGII-V) were compared with rats also receiving TCV-116 (ANGII-TCV). In both groups, blood pressure was similar and significantly higher than in control rats. The preproET-1, ET(A) receptor and PDGF A-chain expressions in the left ventricle were significantly increased in ANGII-V compared with control rats, and were significantly suppressed in ANGII-TCV compared with ANGII-V rats. ANGII-V rats showed a significant increase of the type I collagen expression, wall-to-lumen ratio, perivascular fibrosis, and myocardial fibrosis, with all these parameters being significantly improved by TCV-116. Myocardial remodeling in Ang II-induced hypertensive rats was significantly ameliorated by a subdepressor dose of TCV 116, which may have been due to a decrease in ET-1 and PDGF A-chain expression in the left ventricle. PMID- 11213032 TI - Acute effects of E-3174, a human active metabolite of losartan, on the cardiovascular system in tachycardia-induced canine heart failure. AB - The aim of this study was to evaluate the acute effects of E-3174, a human active metabolite of the AT1 receptor antagonist, losartan, on hemodynamic functions in dogs with severe heart failure (HF). In dogs, insignificant plasma levels of E 3174 are present following administration of losartan, and therefore, the effects of these two drugs can be studied independently in the dog. HF was established by rapid pacing of the right ventricle (250-270 beats/min) for 4 weeks. We examined changes in cardiovascular functions after acute intravenous administration of losartan (1 mg/kg) and E-3174 (0.3 and 1 mg/kg), as well as an ACE inhibitor, enalapril (0.3 and 1 mg/kg), under condition of HF. The HF before treatment was characterized by increases in pre- and after-load of the left ventricle (LV), consequent low cardiac output, and LV dilatation. E-3174 at 0.3 and 1 mg/kg reduced pulmonary artery pressure (-13+/-6% and -22+/-3% from baseline, respectively, p<0.05), pulmonary capillary wedge pressure (-18+/-4% and -36+/ 10%, p<0.05) and mean arterial pressure (-24+/-2% and -36+/-7%, p<0.05), increased stroke volume (SV: +12+/-7% p>0.05; +36 +/-19%, p<0.05), and reduced peripheral resistance (-23+/-5% and -41+/-9%, p<0.05), but had no effect on the first derivative of left ventricular pressure (dP/dt/P) or the time constant for relaxation. Effects of losartan at 1 mg/kg were similar to those of 0.3 mg/kg of E-3174. Enalapril at 1 mg/kg caused changes comparable to those seen after E-3174 administration (1 mg/kg), except that the increase in SV (+16+/-8%, p<0.05) with enalapril was not as great as that with E-3174. Both losartan at 1 mg/kg and E 3174 at 0.3 and 1 mg/kg increased fractional shortening to a similar extent (FS: +52+/-12%, +47+/-8% and +56+/-8%), while enalapril at 0.3 and 1 mg/kg had no significant effects on FS. Reflex elevation of plasma renin activity induced by 1 mg/kg of E-3174 was similar to that caused by 1 mg/kg of enalapril, suggesting that the two drugs achieved similar inhibition of the endogenous renin angiotensin system. Our study demonstrated that acute blockade of the AT1 receptor with E-3174 reduced elevated pre- and after-load and consequently increased stroke volume in a canine HF model. With the exception of changes in stroke volume, these effects of E-3174 were comparable to those produced by enalapril, and were 3 times stronger than those by losartan. PMID- 11213033 TI - Coronary capillary remodeling in non-insulin-dependent diabetic rats: amelioration by inhibition of angiotensin converting enzyme and its potential clinical implications. AB - Using Otsuka Long Evans Tokushima Fatty (OLETF) rats, a model of human non insulin-dependent diabetes mellitus (NIDDM) that exhibits hypertension, obesity, hyperglycemia and hyperlipidemia, the role of local angiotensin II in cardiovascular complications at early stages of NIDDM was characterized. OLETF rats were given an angiotensin converting enzyme (ACE) inhibitor, cilazapril (10 mg/kg/day) or vehicle from the age of 5 weeks to 20 weeks. Arteriolar, intermediate and venular capillary proportions were determined by the double staining method and levels of collagen and non-collagenous proteins were determined by the selective dye-binding method in heart tissues. In OLETF rats at 20 weeks of age, capillary network remodeling (i.e., an increase in arteriolar portions and a decrease in venular portions) and an increase in collagen content were detected. Cilazapril not only exerted favorable effects on markers of diabetes, but also prevented capillary network remodeling and ameliorated the increase in collagen content. These results suggest that 1) capillary network remodeling and increase in extracellular matrix protein levels precede the onset of overt NIDDM in OLETF rats, and 2) angiotensin II may be involved in the pathogenesis of cardiac complications in the early stages of NIDDM. PMID- 11213034 TI - A case of renovascular hypertension due to bilateral renal artery microaneurysm who succeeded in baby delivery. AB - We report the case of a young pregnant woman with bilateral renovascular hypertension due to renal microaneurysms from an unknown cause, who had a successful delivery. Pregnancy did not affect the disease activity even in the postpartum period. Her blood pressure was maintained within the normal range by administration of labetalol. Although the angiographic appearance of the symmetrical aneurysms in both renal artery beds from the interlobular to arcuate artery levels suggested polyarteritis nodosa of multiple microaneurysms in the bilateral interlobular arteries, the clinical features suggested other causes of renovascular hypertension, such as fibromuscular dysplasia and/or congenital microaneurysms. We were thus unable to reach a definitive diagnosis. PMID- 11213035 TI - Endoscopic subtotal thyroidectomy for patients with Graves' disease. AB - Endoscopic thyroidectomy performed via the precordial approach leaves no scarring of the neck, and thus provided excellent results from a cosmetic viewpoint. We applied this technique to perform subtotal thyroidectomy in 12 patients with Graves' disease. Three trocars were inserted in the precordial region, and endoscopic surgery was performed with carbon dioxide insufflation. Vessel management and thyroidectomy were carried out using ultrasonic coagulation devices. The mean operative time was 259.8 min, and the mean blood loss was 90.2ml. There were no postoperative complications such as subcutaneous emphysema or hemorrhage, although hypoparathyroidism and recurrent laryngeal nerve paralysis occurred in one patient. Cosmetically esthetic results were achieved in all patients. These findings indicate that this surgical technique represents an effective method of treating Graves' disease that provides excellent cosmetic results. PMID- 11213036 TI - Pneumatic stabilization for flail chest injury: an 11-year study. AB - The use of prolonged mechanical ventilation in the treatment of flail chest injury may increase the incidence of pulmonary morbidity. The aim of this study was to examine the results of performing internal pneumatic stabilization in our hospital. A retrospective review of the medical records of 59 patients with flail chest injury who presented within an 11-year period was conducted. During the second half of the period examined, we routinely adopted three characteristic procedures in the treatment of flail chest injury, namely, pressure support on spontaneous breathing, continuous positive airway pressure via a mask, and respiratory physical therapy by physical therapists. We compared the background, prognosis, and methods of treatment for flail chest injury before and after the introduction of these three procedures. A marked decline in the duration of endotracheal intubation and controlled mechanical ventilation, and in the frequency of pulmonary morbidity, was evident following the introduction of the above procedures. PMID- 11213038 TI - Annuloaortic repair in the treatment of aortic regurgitation and aortic root pathology. AB - We developed a new technique of aortic root repair which may be able to eliminate the potential problem of leaflet damage, resulting from the direct contact of the aortic leaflets with synthetic vascular grafts during systole. This report describes our technique of annuloaortic repair and the operative results. Between February 1995 and October 1998, 13 patients underwent annuloaortic repair. The patients included 8 males and 5 females (mean age 50 years). Four patients had grade IV/IV aortic regurgitation (AR), 5 had III/IV AR, 2 had II/IV AR, and 1 had no AR preoperatively. Regarding the preoperative functional status, 1 patient was classified as New York Heart Association class IV, 5 were class III, 6 class II, and 1 class I. Concomitant cardiovascular procedures were performed in 12 cases. Aortic valvuloplasty or annuloplasty was performed in 7 patients. Both operative and short-term postoperative results with pre- and postoperative echocardiographic findings were studied retrospectively. The mean total cardiopulmonary bypass time was 212 min. The mean aortic cross-clamp time was 130 min. Circulatory arrest was induced in 5 patients. Postoperatively, 7 patients had no AR. Three patients had grade I/IV AR and 3 had grade II/IV AR. Perioperative changes in aortic annulus, mid-sinus portion, and sinotubular junction diameters were determined echocardiographically in 5 patients. The preoperative diameters were 2.7 +/- 0.4, 5.4 +/- 0.5, and 4.7 +/- 1.0 cm, respectively. The postoperative diameters were 2.3 +/- 0.5, 4.2 +/- 0.5, and 3.5 +/- 0.5cm, respectively. Ten patients were class I and 2 were class II. This technique of annuloaortic repair with or without aortic valvuloplasty is applicable to a certain subset of patients with aortic root disease and AR. Both the indications for this procedure and the long-term results should be confirmed. PMID- 11213037 TI - Treatment for aortic graft infection. AB - Nine patients with an aortic graft infection presented after undergoing aortic grafting. Seven of 9 patients underwent an initial aortic reconstruction in our hospital. The incidence of aortic graft infection was 1.5% (7/456). There were 6 cases of paraprosthetic infection and 3 cases of aortointestinal fistulas. The treatments consisted of a complete graft excision and an axillofemoral bypass in 6 patients, a complete graft excision alone, a partial graft excision and a femorofemoral bypass, and the preservation of the graft with omental wrapping and irrigation in 1 each. Broad-spectrum antibiotics were intravenously administered to all patients and were then replaced by selective antibiotics for the responsible organisms. All surviving patients received antibiotics orally for 3-6 months. The early postoperative mortality rate was 11.1%. Aortoduodenal fistula occurred in 1 patient with graft excision alone. Graft thrombosis occurred in 2 patients with an axillofemoral bypass. No late graft infection or stump blowout occurred in any patient. We believe that a complete excision of the infected graft as well as the maintenance of distal tissue perfusion is necessary. However, based on the condition of the patient, the appearance of the operating field, and the difficulty of a repeat operation, we would like to stress the importance of selecting the best and safest treatment plan for each case. PMID- 11213039 TI - Penetrating atherosclerotic ulcer. AB - The pathogenesis of penetrating atherosclerotic ulcer (PAU) in aortic disease remains controversial. Between January 1995 and April 1999, five patients underwent treatment for a PAU in our hospital. All were men, ranging in age from 46 to 74 years, with a mean age of 66.2 years. The PAU was located on the thoracic descending aorta in three patients and on the abdominal aorta in two. Preoperative diagnosis was established by contrast-enhanced computed tomographic scan and aortogram. Surgery was performed in four patients, as graft replacement in three, and patch plasty in one. The remaining patient is being carefully observed on antihypertensive therapy. No connective tissue disorder, trauma, dissection, or infection was seen in any of the patients who underwent surgery, all of whom had uneventful postoperative courses with no perioperative complications or enlargement of the aorta. We conclude that surgical treatment should be performed for patients with PAU to prevent an aortic catastrophe caused by rapid development of the lesion. This report might provide further evidence of the importance of PAU. PMID- 11213040 TI - Management of esophageal perforation. AB - Despite recent advances in thoracic surgery, the management of esophageal perforation remains problematical and controversial. Thirty-one patients were treated for an esophageal perforation between 1986 and 1998. The esophageal perforation was iatrogenic in 25 cases, spontaneous in 2, traumatic in 2, and caused by a tumor and tuberculous lymphadenitis in 2 patients. There were 10 cervical, 19 thoracic, and 2 abdominal perforations. The interval from perforation to operation was less than 24h in 12 patients and more than 24h in 19 patients. The surgical procedures included a primary repair in 12 patients, a resection in 8, and conservative treatment with minor surgical approaches in 11. The mortality rate was 20% (4/20 patients) in the surgical treatment group and 45.5% (5/11 patients) in the conservative treatment with minor surgery group. The overall mortality was 29% (9/31 patients). The prognosis is thus concluded to depend on the cause and location of the perforation, the presence of underlying esophageal diseases, and the surgical procedure chosen. PMID- 11213041 TI - A new procedure of percutaneous microwave coagulation therapy under artificial hydrothorax for patients with liver tumors in the hepatic dome. AB - Percutaneous microwave coagulation therapy (PMCT) has been widely used as an effective minimal invasive therapy for small liver tumors. The occurrence of a sonographic masked space due to the presence of the lung, however, has become a major obstacle to visualizing the whole tumor in the hepatic dome. To facilitate the use of PMCT for liver tumors in the hepatic dome, we developed PMCT in combination with the artificial hydrothorax method (percutaneous transdiaphragmatic MCT: PTD-MCT). Our new approach for PMCT to the hepatic tumors located in Couinaud's segments VIII or VII just under the diaphragm resulted in a successful treatment. The separation of the lung from the diaphragm by the infusion of saline into the pleural cavity enabled us not only to visualize the whole tumor in the hepatic dome to accurately target the tumor, but also helped us to avoid injuring the lung. PTD-MCT is therefore strongly recommended for the treatment of liver tumors in the hepatic dome. PMID- 11213042 TI - The role of endoscopic procedures in the management of postcholecystectomy and posttraumatic biliary leak. AB - Endoscopic retrograde cholangiopancreatography (ERCP) is an important tool in the evaluation of the biliary system. It not only diagnoses the site of biliary leak following bile duct injury, but it also acts as a therapeutic modality to allow interventional procedures such as sphincterotomy, nasobiliary drainage, or stent placement to be performed. The present study was carried out to evaluate the role of endoscopic management of biliary leak, following either liver trauma or cholecystectomy. Of a total 21 patients with bile leak following liver trauma and biliary surgery, 20 were managed by various endoscopic procedures. In the postcholecystectomy group, ERCP revealed a cystic duct leak in 9 patients and common bile duct injury in 6 patients. These complications were managed by sphincterotomy alone in 2 patients, by nasobiliary drainage alone in 4 patients, by sphincterotomy and nasobiliary drainage in 8 patients, and by sphincterotomy and stent placement in 1 patient. Posttraumatic biliary fistula was successfully managed by performing sphincterotomy followed by the placement of nasobiliary drainage in all of five patients who had suffered trauma injury. PMID- 11213043 TI - Diaphragmatic injuries in childhood. AB - The early detection and surgical repair of diaphragmatic injury is vital for saving the life of symptomatic children suffering from trauma. Furthermore, an accurate diagnosis may be difficult, particularly in right-sided diaphragmatic injuries. Fifteen children with diaphragmatic injury treated at our department between 1977 and 1998 were evaluated retrospectively. They included 9 boys and 6 girls, and consisted of 8 left- and 6 right-sided injuries, and 1 midline retrosternal injury, due to a blunt (n = 13) or penetrating (n = 2) trauma. The most frequent symptoms were dyspnea (86.6%), and abdominal pain and vomiting (13.4%). The diagnosis was confirmed preoperatively in 13 patients based on chest X-ray (n = 7), gastrointestinal series (n = 3), barium enema (n = 1), and computed tomography and/or ultrasonography findings (n = 2). Among these, a diagnostic delay occurred in 3 patients with right-sided injuries. A primary repair was performed through a laparotomy (n = 14) or thoracotomy (n = 1). Postoperative intussusception was the most frequent complication (n = 2). Diaphragmatic injury must be considered in any child who has sustained a thoracoabdominal trauma. Serial chest X-rays should be taken especially in right sided injuries in which a considerable diagnostic delay may occur. Further radiological methods may be necessary to confirm the diagnosis. In addition, postoperative intussusception may be encountered following diaphragmatic repair. PMID- 11213045 TI - Successful surgical removal of an intrapulmonary aberrant needle under fluoroscopic guidance: report of a case. AB - We describe herein the successful surgical removal of an intrapulmonary aberrant needle. An asymptomatic 47-year-old woman underwent a routine chest X-ray which revealed a needle located in the right S8 area. We first tried to extract the needle; however, fluoroscopic examination confirmed that it had broken into two pieces and therefore, partial resection of the right S8 was performed. To avoid rethoracotomy, the operation was done under fluoroscopic guidance. An intrathoracic aberrant needle should always be removed surgically as soon as possible, even if the patient is asymptomatic, due to the possibility of its migration into the vessels and the development of lung abscess or pyothorax. PMID- 11213044 TI - Intrathoracic aneurysm of the innominate and right subclavian arteries: report of a case. AB - Aneurysms of the innominate and subclavian arteries are uncommon but associated with high mortality rates. We report herein the case of a 45-year-old man who presented with facial anhidrosis that developed several years after blunt thoracic trauma, in whom an aneurysm involving the innominate and subclavian arteries was revealed by preoperative examinations. Resection of the aneurysm and reconstruction from the ascending aorta to both the subclavian and common carotid arteries using a bifurcated graft was successfully performed without brain perfusion. Although the left posterior cerebral artery, which was not manipulated during surgery, became occluded, it was recanalized by thrombolysis. The patient was discharged in good health and has remained well since. PMID- 11213046 TI - Laryngotracheo-esophageal cleft in a neonate with esophageal atresia and tracheo esophageal fistula: report of a case. AB - Laryngotracheo-esophageal cleft (LTEC) is a congenital anomaly, rarely found in neonates with esophageal atresia (EA) and tracheo-esophageal fistula (TEF), that poses diagnostic and treatment dilemmas for the attending surgeon. In most cases previously reported, the diagnosis of this association was made either at surgery or at autopsy. We present herein the case of a neonate with EA and distal pouch (type C) TEF who was also found to have a LTEC (Evans type III) at the time of surgery. The salient clinical and radiological features of this association are highlighted to increase awareness of the possibility of this rare association and to help promote its early detection. PMID- 11213047 TI - Complete cure of malignant lymphoma of the stomach with a huge adrenal lesion achieved by preoperative chemotherapy and surgery: report of a case. AB - We report herein the case of a 53-year-old woman with malignant lymphoma of the stomach who was successfully treated by preoperative chemotherapy and surgery. The patient consulted our hospital with the chief complaint of upper abdominal pain. Endoscopy demonstrated a protruding lesion at the antral posterior wall of the stomach, and a post-biopsy pathological diagnosis of diffuse large cell type B-cell lymphoma was established. Moreover, abdominal ultrasonography, computed tomography, and magnetic resonance imaging demonstrated a tumor measuring approximately 10cm in diameter in the left adrenal gland. A total of three courses of chemotherapy using the CHOP regimen were given preoperatively. The CHOP regimen consisted of 100mg of prednisolone administered for 8 days together with 1.9mg of vincristine, 1,000mg of cyclophosphamide, and 60mg of epirubicin administered intravenously on the first day. This resulted in tumor shrinkage, and a distal gastrectomy, lymph node dissection, and left adrenalectomy were subsequently performed. Since the pathological findings of the resected tissue specimen demonstrated complete elimination of the malignant lymphoma, this combination of procedures was defined as having resulted in a complete response. The postoperative course of this patient was uneventful. She is still alive without any sign of tumor recurrence 6 years after her operation, and is being followed up at the outpatient clinic. PMID- 11213048 TI - Penetration of the duodenum by an ingested needle with migration to the pancreas: report of a case. AB - A case of a penetration of the duodenum by a needle with migration to the pancreas in a 50-year-old man is reported herein. The patient was referred to us with a chief complaint of diarrhea. An abdominal plain roentgenogram showed a needle in the upper abdominal area. An abdominal computed tomography scan and contrast X-ray revealed the foreign body to be located outside of the duodenum and in the head of the pancreas. An emergency operation was therefore performed on the first day and the needle in the head of the pancreas was thus extirpated safely. A perforation of the gastrointestinal tract by an ingested foreign body is difficult to accurately and quickly diagnose when no peritonitis or abscess formation is observed. Therefore, the use of contrast X-ray is considered to be useful in the diagnosis of such a perforation. PMID- 11213049 TI - Cystic duplication of the cecum with segmental dilatation of the ileum: report of a case. AB - Duplication cyst and segmental dilatation are rare congenital anomalies of the gastrointestinal tract, both of which are known to result in intestinal obstruction. We describe herein a case of intestinal obstruction in a neonate, caused by a duplication cyst in the cecum. A small dilated segment of ileum was also present at the site where Meckel's diverticulum would be expected, which was not causing obstruction to the luminal contents. Although it is well known that either of these conditions may coexist with a number of congenital malformations, their concurrent occurrence has never been reported before. PMID- 11213050 TI - Pneumoperitoneum following the spontaneous rupture of a gas-containing pyogenic liver abscess: report of a case. AB - We report herein the case of a ruptured liver abscess that resulted in pneumoperitoneum. A patient with diabetes mellitus presented with symptoms of acute abdomen. The plain abdominal radiograph and computed tomography findings revealed abdominal free air and a gas-containing liver abscess, whereby a diagnosis of a ruptured liver abscess was made. An emergency operation was performed, and the abscess was drained followed by peritoneal lavage and the administration of appropriate antibiotics. To the best of our knowledge, very few cases of spontaneous pneumoperitoneum occurring secondary to the rupture of a gas containing liver abscess have been encountered in Japan. PMID- 11213051 TI - Malignant pheochromocytoma with hepatic metastasis diagnosed 10 years after a resection of the primary incidentaloma adrenal lesion: report of a case. AB - A 40-year-old woman developed hepatic tumors 10 years after a resection of pheochromocytoma of the left adrenal gland. Computed tomography showed a round tumor measuring about 35mm in diameter at segment V of the liver (Couinaud's classification), and magnetic resonance imaging showed another tumor measuring about 5mm at segment V-VIII of the liver. The results of the endoscopic examination of her upper gastrointestinal tract and barium enema were normal. Owing to a suspected hepatic metastasis of malignant pheochromocytoma, a right lobectomy of the liver was performed. Postoperatively, [131I]metaiodobenzylguanidine scintigram and computed tomography showed no other residual tumors nor metastasis. The present case suggests that a long-term follow up only by endocrinological examinations is insufficient to find newly developed metastatic foci, while routine diagnostic imaging at frequent intervals is necessary in cases of pheochromocytoma. PMID- 11213052 TI - Ruptured dissecting aneurysm in bilateral iliac arteries caused by Ehlers-Danlos syndrome type IV: report of a case. AB - Ehlers-Danlos syndrome (EDS) is an inherited disorder of connective tissue characterized by hyperextensible skin, hypermobile joints, and abnormalities of the cardiovascular system. Ten types and several subtypes of EDS have so far been recognized based on genetic, clinical, and biochemical characteristics. The spectrum of the disorder varies from mild to life-threatening vascular complications. EDS type IV is a particularly dangerous form with a lethal spontaneous rupture of the major arteries and aneurysmal formation. We present herein a case of a ruptured dissecting aneurysm in the bilateral iliac arteries caused by EDS type IV. A previously healthy 33-year-old man without any physical features of this connective tissue disorder experienced a metachronous vascular rupture two times. Successful synthetic bypass grafting was performed with great difficulty. The diagnosis of EDS type IV was made afterwards based on an electrophoresis analysis of a skin biopsy specimen which revealed a lack of type III collagen. Surgical intervention in cases of arterial complications in EDS type IV patients have been reported to be both difficult and frequently unsuccessful. The early clinical recognition of this syndrome is therefore of great importance due to the hazards of such surgical therapies. PMID- 11213053 TI - Billroth I gastrectomy using a circular stapler to treat gastric cancer. AB - We describe herein our technique of performing gastrectomy followed by side-to end gastroduodenostomy. Because the clamp is removed at the resection line of the greater curvature, there is no need to perform an additional gastrotomy for insertion of the instrument. This feature differentiates our technique from previous methods of anastomosis using the circular stapler. We believe that our technique is superior in simplicity and security to the traditional hand-sewn anastomosis. Moreover, it allows for a shorter operative time. This technique is recommended for practical surgery over conventional techniques. PMID- 11213054 TI - Laparoscopic right hemicolectomy with radical lymph node dissection using the no touch isolation technique for advanced colon cancer. AB - The treatment of advanced right-sided colon cancer presents numerous challenges for the surgeon who must aim to minimize the invasiveness of surgery, achieve curative resection, and prevent port-site recurrences. To overcome these issues, we performed a totally intra-abdominal laparoscopic right hemicolectomy with radical lymph node dissection based on a no-touch isolation technique. To perform this no-touch technique, we initially dissected the lymph nodes along the surgical trunk, then transected the transverse colon, terminal ileum, and mesentery without tumor manipulation. Finally, the right side of the colon was freed retroperitoneally. We performed this surgical technique on three patients and no intraoperative complications were encountered. Curative resection was achieved in all three patients, as curability A according to the Japanese Classification of Colorectal Carcinoma, and their postoperative courses were uneventful. Therefore, this novel technique proved to be both feasible and safe. Furthermore, it enabled us to minimize the invasiveness of surgery, while providing clear access to resect the right-sided advanced colon cancer. PMID- 11213055 TI - Could inducible nitric oxide synthase inhibitors improve the survival and long term function of intraportal islet grafts? PMID- 11213056 TI - Prevention of early islet graft failure by selective inducible nitric oxide synthase inhibitors after pig to nude rat intraportal islet transplantation. AB - BACKGROUND: Clinical and experimental data indicate that early failure of intraportally grafted islets is caused by inflammation including secretion of cytokines and nitric oxide. Direct inducible nitric oxide synthase suppression may avoid detrimental effects associated with steroid administration. We compared the efficiency of selective and unselective inducible nitric oxide synthase inhibitors with dexamethasone to suppress nitric oxide generation after intraportal islet xenotransplantation into nude rats. METHODS: Nonfasting serum glucose levels were daily evaluated after intraportal transplantation of 4000 freshly isolated pig islets into diabetic nude rats (85 mg/kg streptozotocin) either sham-treated with saline (n=21) or continuously infused for 7 days with L NG-monomethyl-arginine (n=7), S-methyl-isothiourea (n=15), or S-(2-aminoethyl) isothiourea (n=19) in a dosage of 240, 100, or 50 mg/kg/day, respectively. Dexamethasone was injected i.p. twice as a daily bolus of 20 mg/kg (n=10) starting 1 day pretransplant. The nitrate/nitrite serum level was quantified colorimetrically 0, 24, and 48 hr posttransplant. RESULTS: Saline treatment partially resulted in graft function (4/21) throughout the observation period (21 days). L-NG-monomethyl-arginine-treated rats showed sustained hyperglycemia (0/7) not different from diabetic controls. Normoglycemia was observed after treatment with dexamethasone (6/10, P<0.05 versus saline and L-NG-monomethyl-arginine), S methyl-isothiourea (10/15, P<0.01), or S-(2-aminoethyl)-isothiourea (15/19, P<0.001). Graft function was associated with complete suppression of nitric oxide generation after S-methyl-isothiourea and S-(2-aminoethyl)-isothiourea treatment (P<0.001 versus saline) and partial suppression after dexamethasone treatment (P<0.05). CONCLUSIONS: Our observation of long-term function of xenogeneic islets in an inflammatory environment without interference of reactive T cells revealed the potency of highly selective isothioureas to completely suppress inducible nitric oxide synthase making reduction of islet-toxic immunosuppression feasible. PMID- 11213057 TI - Protection against gas exchange abnormalities by pre-aerosolized PGE1, iloprost and nitroprusside in lung ischemia-reperfusion. AB - BACKGROUND: Development of severe gas exchange abnormalities and respiratory failure is a major threat in lung transplantation. METHODS: We used a model of ischemia-reperfusion injury in buffer-perfused rabbit lungs, with gas exchange conditions being analyzed in detail by the multiple inert gas elimination technique. A total of 150 min of warm ischemia was performed, and anoxic ventilation and a positive intravascular pressure were maintained throughout the ischemic period. RESULTS: Reperfusion provoked a transient, mostly precapillary pulmonary artery pressure elevation and progressive lung edema formation attributable to increased capillary permeability. Severe ventilation-perfusion mismatch with predominance of shunt flow became apparent within minutes after onset of reperfusion. 5 min-aerosolization maneuvers for alveolar deposition of prostaglandin E1, the long-acting prostacyclin analogue iloprost or the nitric oxide donor agent sodium nitroprusside were undertaken at the onset of ischemia. All preaerosolized vasodilator agents markedly reduced the pulmonary artery pressure elevation and the leakage response upon reperfusion. Most impressively, maintenance of physiological ventilation-perfusion matching was achieved by these maneuvers, and the development of shunt flow was largely suppressed. CONCLUSIONS: Preischemic alveolar deposition of PGE1, iloprost, and sodium nitroprusside by aerosol technique is highly effective in conserving normal pulmonary hemodynamics, microvascular integrity, and physiological gas exchange conditions upon reperfusion. This approach may offer as new strategy for maintenace of pulmonary function in lung transplantation. PMID- 11213058 TI - V-PYRRO/NO: an hepato-selective nitric oxide donor improves porcine liver hemodynamics and function after ischemia reperfusion. AB - BACKGROUND: The role of nitric oxide (NO) in ischemia reperfusion (I/R) injury is controversial as both beneficial and harmful effects have been reported. We explored the potential role of a pharmacological agent recently shown to generate NO metabolically in the liver in an animal model of transplantation. METHODS: The effect of a selective hepatic NO donor, O2-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium 1,2-diolate (V-PYRRO/NO), on hepatic hemodynamics and biliary function was evaluated in both the in situ and I/R pig liver. RESULTS: V-PYRRO/NO significantly reduced in situ hepatic vascular resistance (HVR) without altering systolic blood pressure. Portal vein flow was essentially unchanged during in situ infusions while hepatic artery flow nearly doubled (P=0.03). After I/R, V PYRRO/NO infusions significantly reduced both portal vein pressure (PVP) and HVR (P=0.04). Also, serum bile acid clearance increased from 15% when taurocholate (TC) was infused alone to 46% (P=0.007) when infused simultaneously with V PYRRO/NO. Aqueous bile production tripled with TC and V-PYRRO/NO as compared to TC alone (P=0.04). Analysis of bile outputs revealed a significant increase in biliary cholesterol, biliary phospholipid, and biliary bile acid (P<0.05) with V PYRRO/NO infusion. CONCLUSIONS: The hepato-selective nitric oxide donor, V PYRRO/NO, reduced hepatic resistance parameters of the pig liver both before and after I/R and improved the plasma clearance of bile acid and biliary outputs of bile acid-dependent compounds. The augmented function observed after I/R may be due to improvements in hepatic blood flow secondary to altered hepatic hemodynamics. PMID- 11213059 TI - Transplantation of infantile bladder in rats: an alternative procedure for bladder augmentation. AB - BACKGROUND: Our purpose was to evaluate whether bladder transplantation (BTx) can be used for bladder augmentation (BA). METHODS: Bladders from infantile Brown Norway rats (less than 21 days old) were excised and each transplanted into a pouch created in the distal omentum of a 6-week-old Lewis rat (fully allogeneic BTx). No immunosuppressant was used in group I (n=12). Intramuscular FK506 was used daily from the day of BTx in group II (n=16; 0.2 mg/kg), group III (n=22; 0.6 mg/kg), and group IV (n=16; 1.2 mg/kg) until harvesting 3, 4, 5, or 6 weeks after BTx. FK506 was used for only 2 weeks in group V (n=12; 0.6 mg/kg/day) and group VI (n=12; 1.2 mg/kg/day). Syngeneic bladder transplants acted as controls (n=16). Hematoxylin and eosin staining was used to examine all grafts. In six rats from group III, BA was performed by anastomosing the graft to the recipient bladder 10 days after BTx. RESULTS: Each successfully transplanted graft appeared macroscopically as a thin-walled cyst. Rejection was seen in all grafts from groups I, II, V, and VI, and was minimal or absent in groups III and IV. On medium to long-term follow-up the only side effect of FK506 observed was reduced weight gain. Graft survival in the control group was 100%. BA was successful in all six cases, and the mucosa was normal throughout each augmented bladder. CONCLUSIONS: This is the first report of the successful transplantation of infantile tissue without vascular anastomosis. Because of the efficient, safe immunosuppression possible with FK506, our BTx technique could find clinical application for creating viable vesical tissue that could be used for BA. PMID- 11213060 TI - Islets in alginate macrobeads reverse diabetes despite minimal acute insulin secretory responses. AB - BACKGROUND: Encapsulation of islets has been widely investigated as a treatment for diabetes. The characteristics and dynamics of insulin secretion by encapsulated islets in response to glucose and other secretagogues are not well understood. METHODS: In our study, macroencapsulated syngeneic islets at 3-4 wk after transplantation were studied for insulin release in response to i.v. glucose (hyperglycemic clamps at 250 or 350 mg/dl plasma glucose), arginine (i.v. bolus, 100 mg/kg), glucagon-like peptide-1 (i.v. infusion for 20 min, 2.2 pmol/kg/min), and meal challenge. Syngeneic islets (6000 islets) were encapsulated in alginate macrobeads (2-3 mm diameter) with or without poly-L lysine coating and transplanted into the peritoneal cavity of STZ-diabetic Lewis rats. Normal (nontransplanted) and diabetic Lewis rats transplanted with "naked" islets under the kidney capsule served as controls. RESULTS: Animals transplanted with macrobeads displayed subnormal insulin responses to glucose, arginine, and glucagon-like peptide-1 despite achieving normoglycemia faster than animals with renal subcapsular islet transplants. Plasma insulin responses to meal challenges were blunted in animals with macrobeads resulting in increased plasma glucose excursions. CONCLUSIONS: We conclude that, after transplantation into diabetic Lewis rats, macroencapsulated islets have significantly impaired insulin secretion despite achieving normal fed glycemic levels. PMID- 11213061 TI - The use of the endothelin receptor antagonist, tezosentan, before or after renal ischemia protects renal function. AB - BACKGROUND: Utilization of organs subjected to ischemia/reperfusion (I/R) injury could expand the donor pool. Endothelin (ET) is implicated in renal I/R injury. Therefore, our study compared the effectiveness of pre- and postischemic administration of the ET receptor antagonist, Tezosentan, in preserving renal function. METHODS: In a rat model, a kidney was subjected to 45 min of ischemia along with a contralateral nephrectomy. After 24 hr of reperfusion, renal function was assessed by serum creatinine (Scr), inulin clearance (glomerular filtration rate; GFR), and histology. ET-1 peptide expression was localized using immunohistochemistry. Three groups were studied: I/R untreated (n=17), I/R pretreated (n=11), and I/R posttreated (n=13) with Tezosentan (15 mg/kg, i.v.). RESULTS: Tezosentan significantly decreased (P<0.05) the rise in Scr from I/R injury (2.0+/-0.4 mg/dl, before and 2.9+/-0.4 mg/dl, after treatment) compared with untreated animals (4.2+/-0.4 mg/dl). GFR was significantly increased (P<0.05) from 0.13+/-0.03 ml/min (untreated animals) to 0.74+/-0.16 and 0.47+/ 0.14 ml/min (pre- and posttreated animals). Untreated animals had significant cortical acute tubular necrosis, which was almost completely prevented by pretreatment with Tezosentan and markedly reduced by posttreatment. Increased ET 1 peptide expression was noted in the renal vasculature and in the cortical tubular epithelium of kidneys exposed to I/R. CONCLUSIONS: The purpose of this study was to optimize the function of kidneys exposed to I/R injury. Pretreatment as well as posttreatment with Tezosentan successfully decreased Scr, increased GFR, and maintained renal architecture in kidneys after ischemia. Therefore, ET receptor antagonists may be useful to preserve renal function in the transplantation setting. PMID- 11213062 TI - Heart and liver xenotransplantation under low-dose tacrolimus: graft survival after withdrawal of immunosuppression. AB - BACKGROUND: The hamster-to-rat xenotransplantation model is a useful model to investigate the features of extended host response to long-surviving xenografts. Early xenoantibody responses are T-cell independent and resistant to tacrolimus. Treatment with the combination of mofetil mycophenolate plus FK506 avoids acute xenograft rejection completely, but after withdrawal of immunosuppression hamster grafts are rejected by a process called late xenograft rejection (LXR). METHODS: Hamster hearts and livers were transplanted into Lewis rats. Grafted rats were treated with mofetil mycophenolate (25 mg/kg/day) for 8 days and FK506 (0.2 mg/kg/day) for 31 days. Serum IgM and IgG levels were determined by flow cytometry and interferon-gamma levels by ELISA. IgM, IgG, and C3 deposits were measured in tissue by immunofluorescence, and leukocyte infiltration was measured by immunoperoxidase staining. Results. Survival of heart and liver xenografts in the rats was 48+/-4 days and 63+/-8 days, respectively. After cessation of all immunosuppression, hearts were rejected in 18+/-4 days and livers in 33+/-8 days. Production sequences of xenoantibodies in the two organs differed substantially, especially 7 days after transplantation and at the moment of rejection. Quantification of interferon-gamma levels indicated that there were no significant changes after transplantation. Histological and immunohistochemical studies showed signs of humoral mechanism of LXR in rats undergoing heart transplantation and cellular mechanism of LXR in those that received a liver transplant. Conclusions. These observations suggest that rejection in the hamster to-rat heart xenotransplantation model is mediated by a T cell-independent B-cell response to which a T cell-dependent B-cell response is added in LXR. In the liver xenotransplantation model, our hypothesis is that LXR is mediated by a mixed cell mechanism, involving lymphocytes CD4+ CD45RC+, macrophages, and cytotoxic T lymphocytes. In summary, we have demonstrated and compared the peculiar features of LXR in two different organs. PMID- 11213064 TI - Ethnic differences in clinical response to corticosteroid treatment of acute renal allograft rejection. AB - BACKGROUND: Limited in vitro data suggest that African-Americans exhibit greater resistance to corticosteroids than do non-African-American transplant recipients. However, ethnic differences in clinical response to corticosteroids for treatment of acute rejection have not been investigated previously. The purpose of this study was to evaluate the clinical response to corticosteroid treatment for acute rejection in both African-American and non-African-American renal allograft recipients. METHODS: We retrospectively reviewed the medical records of 497 consecutive renal allograft recipients to identify patients who had received corticosteroids as initial treatment of acute rejection. One hundred and twenty patients who received corticosteroids for treatment of acute rejection were evaluated in this analysis. The study population was divided into two groups: the African-American group (n=73) and non-African-American group (n=47). All acute rejection episodes were documented by biopsy and were classified as mild-moderate histologically. Corticosteroid therapy consisted of either methylprednisolone, 500 mg intravenously for 3 days, or oral prednisone, 2 mg/kg/day rapidly tapered over 3 weeks. RESULTS: Twenty-six percent (26%) of African-Americans were considered corticosteroid treatment failures compared to an 8.0% failure rate among non-African-Americans (P<0.05). One-year graft survival was 78% in African American versus 96% in non-African-American (P<0.05). Among African-American and non-African-American recipients, 1-year patient survival rates were 97% and 100, respectively (P=NS). CONCLUSIONS: African-American patients exhibit higher failure rates with corticosteroid treatment of acute rejection. Alternative anti rejection therapies may need to be considered for this "high-risk" patient population to improve long-term graft survival. PMID- 11213063 TI - Use of mycophenolate mofetil as rescue therapy after pediatric liver transplantation. AB - BACKGROUND: Mycophenolate mofetil (MMF) has been increasingly used after liver transplantation (LT) in adults. We report our preliminary experience with MMF as rescue therapy after pediatric LT. METHODS: A total of 19 children received MMF for 21 indications. Median age at LT was 30 months (range 7-149). The median initial oral dose of MMF was 23 mg/kg/day (range 12-43) orally. Median follow-up after initiation of MMF therapy was 642 days (range 229-1606). RESULTS: 1) EFFICACY: MMF was indicated for rejection or insufficient immunosuppression in 16 cases, with normalization of both liver function tests and liver histology in 10 (62%). MMF was successfully used in one patient with post-LT immmune hepatitis and one patient with corticodependence. In three patients with renal function impairment, MMF allowed reduction of cyclosporine A or tacrolimus blood levels, without subsequent rejection. 2) Tolerance: Six patients (32%) experienced eight side effects, mainly gastrointestinal and hematological, which resolved after cessation of MMF in five cases and dose reduction in three. One case of posttransplant lymphoproliferative disease (PTLD) occurred under MMF therapy (5.2%). Four patients had EBV primary infection, while under MMF therapy, without subsequent PTLD. Three patients had CMV primary infection, and five CMV reactivation, under MMF therapy. Seven remained asymptomatic, and one presented with CMV enteritis. CONCLUSIONS: These preliminary results suggest that MMF is an effective and safe immunosuppressant in pediatric LT recipients. Its use is hampered by frequent gastrointestinal and hematological side-effects. MMF does not seem to increase the risk of PTLD nor CMV disease. PMID- 11213065 TI - Live donor renal allograft in end-stage renal failure patients from immunoglobulin A nephropathy. AB - BACKGROUND: The purpose of this study was to attempt to resolve two important issues, i.e. to determine (1) whether the course of recurrent immunoglobulin A nephropathy (IgAN) is benign, and (2) whether it is advisable to use a related donor. METHODS: We evaluated the long-term outcome, in terms of recurrence and graft survival, after live related or unrelated donor renal transplantation, and assessed the validity of the use of related donors in 90 grafts in 89 IgAN patients. RESULTS: Ten-year graft survival for IgAN patients was 66%, compared with 84% for 107 reference recipients who had other kinds of glomerulonephritis (GN), and with 69% in 90 other recipients who had non-GN renal failure (P=0.27). In 43 grafts, 54 event graft biopsies were performed, documenting the presence of mesangial IgA deposits in 19 of those grafts. In eight grafts, lesions were accompanied by chronic rejection (CR). Ten-year cumulative recurrence was 44%. Ten grafts were lost: by CR (n=3) or acute rejection (n=1) in 24 recurrence-free recipients, by CR (n=2) or recurrence (n=2) in 19 recurrent patients, and by patient death (n=2) in 46 patients devoid of graft biopsy. We found no difference in 10-year graft survival between the recurrent and recurrence-free patients (63% vs. 74%, P=0.98), or the proportion of related donors (68% vs. 83%, P=0.25). The presence or matching of HLA B12, B35, or DR4 did not affect the recurrence. CONCLUSIONS: Recurrence increased to 44% with longer follow-up, but this did not limit the graft outcome. Recurrence was not affected by the kind of live donor. We conclude that live related or unrelated kidneys should be offered to IgAN patients. PMID- 11213066 TI - Herbal supplements: a potential for drug interactions in transplant recipients. AB - BACKGROUND: Herbal dietary supplements represent a potential and possibly an overlooked cause for drug interactions in transplant recipients. METHODS: Two patients are reported which suggest that St. John's Wort (SJW) may induce cytochrome P-450 3A4 activity and/or P-glycoprotein expression. Both of these mechanisms are significantly involved in the metabolism and absorption of cyclosporine (CSA) and other immunosuppressants. RESULTS: After two renal transplant recipients started self-medicating with SJW, their CSA concentrations were consistently documented to be subtherapeutic. While on SJW, one patient developed acute graft rejection due to low CSA concentrations. In both patients, termination of SJW returned their CSA concentrations to therapeutic values. CONCLUSIONS: Patients taking SJW concomitantly with CSA or other medications whose absorption and metabolism are mediated by cytochrome P-450 and/or P glycoprotein should require close monitoring. Potential herb-prescription drug interactions are not just limited to SJW. Inquiries regarding the usage of herbal supplements should be an integral component of a transplant recipient's medication history. PMID- 11213067 TI - Hypogammaglobulinemia in lung transplant recipients. AB - BACKGROUND: Infectious complications continue to represent a significant source of morbidity and mortality in lung transplant recipients. Identifying specific, remediable immune defects is of potential value. After one lung transplant patient with recurrent infections was noted to be severely hypogammaglobulinemic, a screening program for humoral immune defects was instituted. The objectives were to define the prevalence of hypogammaglobulinemia in lung transplant recipients, assess levels of antibody to specific pathogens, and correlate infectious disease outcomes and survival with immunoglobulin levels. METHODS: All lung transplant recipients followed at a single center between October 1996 and June 1999 underwent a posttransplant humoral immune status survey as part of routine posttransplant follow-up. This survey consists of total immunoglobulin levels (IgG, IgM, IgA), IgG subclasses (IgG1-4), and antibody titers to Pneumococcus, diphtheria, and tetanus. Since February 1997, this survey has been incorporated into the pretransplant evaluation as well. Humoral survey results for October 1996 through July 1999 were recorded, and clinical information on major infectious disease outcomes was obtained from chart reviews, discharge summaries, the Cleveland Clinic Unified Transplant Database, and review of all microbiological studies and pathology results for each patient. RESULTS: Of 67 patients with humoral immune surveys drawn posttransplant, 47 (70%) had IgG levels less than 600 mg/dl (normal 717-1410 mg/dl), of which 25 (37%) had IgG levels less than 400 mg/dl ("lowest IgG group") and 22 (33%) had IgG levels between 400 and 600 mg/dl ("moderately low IgG group"). A total of 20 patients (30%) had IgG levels of more than 600 mg/dl ("normal IgG group"). Infections that were significantly more common in the lowest IgG group, and more common in the moderately low IgG group than the normal IgG group, included: number of pneumonias (P=0.0006), bacteremias (P=0.02), total bacterial infections (P=0.002), tissue-invasive cytomegalovirus (P=0.01), invasive aspergillosis (P=0.001), total fungal infections (P=0.001), and total infections (P=0.006). Median hospital days per posttransplant year was significantly different in the three groups (11.0 vs. 7.4 vs. 2.8 days, P=0.0003.) Invasive aspergillosis occurred in 44% of the lowest IgG group, 9% of the moderately low IgG group, and 0% of the normal IgG group (P<0.001). Survival was poorest in the lowest IgG group and intermediate in the moderately low IgG group. IgG subclass deficiencies occurred in a variety of patterns. Hypogammaglobulinemic patients lacked protective responses to Pneumococcus in 14/47 (30%), diphtheria in 15%, and tetanus in 19%. In a group of 48 patients screened pretransplant, 90% had normal immunoglobulin levels. CONCLUSIONS: Hypogammaglobulinemia in lung transplant recipients is more common than has been previously recognized. An IgG level of less than 400 mg/dl identifies a group at extremely high risk of bacterial and fungal infections, tissue-invasive cytomegalovirus, and poorer survival. Immunoglobulin monitoring may offer an opportunity for intensive surveillance, tapering of immunosuppression, and preemptive therapy for infection. PMID- 11213068 TI - The effect of aprotinin on renal function in orthotopic liver transplantation. AB - BACKGROUND: In the European Multicenter Study on the Use of Aprotinin in Liver Transplantation (EMSALT), a randomized, double-blind, placebo-controlled, prospective study, we demonstrated that aprotinin significantly reduces intraoperative blood loss during orthotopic liver transplantation (OLT). Aprotinin is metabolized in the kidney and potentially nephrotoxic at high concentrations. Renal insufficiency is a common and serious complication after OLT. It is unknown whether aprotinin increases the risk of renal failure after OLT. METHODS: We analyzed intraoperative urine output, need for postoperative dialysis, perioperative serum creatinine levels, and creatinine clearance in 93 patients enrolled in EMSALT, receiving a high dose of aprotinin, a regular dose, or placebo. RESULTS: Peak increase in serum creatinine exceeding 0.5 mg/dl during one of the postoperative days occurred in 11 (35%) patients in the placebo group, in 11 (34%) patients in the high-dose group, but only in 1 (3%) patient in the regular-dose group (P=0.007). Furthermore, a perioperative decrease in creatinine clearance was seen in the placebo group (-23.9+/-10.1 ml/min) but not in both high-dose (-1.6+/-13.3 ml/min) and regular-dose (9.7+/-10.3 ml/min) groups (P<0.02 comparing regular-dose and placebo group). CONCLUSIONS: Despite its potential nephrotoxicity, the use of aprotinin for reducing blood loss during OLT does not lead to a higher incidence of postoperative renal insufficiency. In combination with the observed reduction in blood loss, these findings support the prophylactic use of regular-dose aprotinin during OLT. PMID- 11213069 TI - Posttransplant diabetes mellitus in pediatric thoracic organ recipients receiving tacrolimus-based immunosuppression. AB - BACKGROUND: Posttransplantation diabetes mellitus (PTDM) is a well-known complication of tacrolimus-based immunosuppression in both adult and pediatric solid organ recipients. The "natural history" of diabetes in the pediatric thoracic transplant population has not yet been described. METHODS: We identified all pediatric thoracic transplant patients receiving tacrolimus-based immunosuppression who developed PTDM. Medical records were reviewed, with a particular focus on the clinical course of PTDM and its relationship to drug weaning. RESULTS: Diabetes developed in 24 of 143 (17%) 30-day survivors of heart (12/96, 13%) and heart-lung/lung (12/ 47, 26%) transplantation. In 17 (71%) patients, the immunosuppressive regimen at the onset of PTDM also included maintenance corticosteroids. Seventeen patients demonstrated glucose intolerance before the onset of diabetes. Nine patients (38%) developed diabetes during pulsed corticosteroid therapy. Median time of onset after transplantation was 9.0 months. All patients required s.c. insulin for glucose control. The median follow up from transplant was 49.9 months. There was a significant decrease in mean tacrolimus dosage (P<0.01), tacrolimus level (P<0.04), and steroid dosage (P<0.02) from onset of PTDM to most recent follow-up. Despite this significant reduction in immunosuppression, only 3/24 (13%) patients were successfully weaned off insulin. CONCLUSIONS: Diabetes mellitus is a common complication in pediatric thoracic transplant patients receiving tacrolimus-based immunosuppression. Insulin dependence in our population rarely resolved, even after lowering tacrolimus and steroid doses. Discontinuation of steroids did not guarantee resolution of diabetes. PMID- 11213070 TI - Evaluation of renal function in potential living kidney donors. AB - BACKGROUND: Most transplant centers in the United States, including our own, use creatinine clearance (Ccr) to estimate glomerular filtration rate (GFR) in potential living kidney donors. The purpose of this study was to evaluate our experience with estimation of donor GFR by Ccr and to explore other potential strategies for evaluation of renal function in donors. METHODS: Potential donors performed one to three outpatient urine collections for Ccr measurement. Those with low or inconsistent results underwent measurement of GFR by a radionuclide method not dependent upon urine collection (rGFR). The ability to determine adequacy of urine volume by creatinine excretion rate (UVcr) was examined. GFR was also predicted from serum creatinine (Scr) by using two prediction equations [Cockcroft-Gault and that from the Modification of Diet in Renal Disease Study (MDRD)]. The effect of indexing GFR by height, as opposed to body surface area (BSA) was explored. RESULTS: Over a 5-year period, 22 potential donors (approximately 10% of total evaluated) had inconsistent or low Ccr. Most had normal rGFR and, presumably, undercollected their urine. However, several female donors had truly low GFR by rGFR. The accuracy of Ccr (compared with rGFR) was not predicted by UVcr in a clinically useful way. The prediction equations did not have sufficient accuracy or precision to replace rGFR in this population. Indexing GFR estimates by BSA introduced a bias toward lower values in females; this was largely overcome by indexing GFR by height. CONCLUSIONS: Evaluation of GFR in potential living donors by Ccr is not very useful. A more promising strategy could be developed predicting GFR from Scr and indexing the results by height rather than BSA. The optimum method for evaluation of renal function in kidney donors deserves further study. PMID- 11213071 TI - Daily interferon therapy for hepatitis C virus infection in liver transplant recipients. AB - BACKGROUND: Hepatitis C virus infection persists after liver transplantation and causes recurrent liver injury in the majority of patients. Standard dose interferon therapy has been largely unsuccessful for hepatitis C in transplant recipients. METHODS: Twelve patients, at least 7 months posttransplant, with detectable hepatitis C virus RNA in serum and features of hepatitis C on liver biopsy were randomized to interferon-alpha2a, 3 mU daily for 12 months (n=8) or no treatment (n=4). The tolerability of daily interferon dosing in liver transplant recipients was evaluated and effects on hepatitis C virus RNA level, quasispecies evolution, and liver histology were studied. RESULTS: Treated patients had an improvement in histological activity index at the end of therapy relative to controls (median reduction of 2 versus median increase of 1.5) (P=0.04). Four treated patients had a virological response (all bDNA negative, one qualitative polymerase chain reaction negative) compared with none of the untreated patients. Only two of six treated patients tested had evidence of quasispecies diversification on therapy. Seven of eight patients in the treatment group required dose reduction for fatigue and/or depression. They tolerated 1.5 mU of interferon-alpha2a daily. Two treated patients developed graft dysfunction, one of who had histological evidence of rejection and subsequent graft loss. CONCLUSIONS: Low daily doses of interferon were tolerated by liver transplant recipients and provided histological benefit without associated quasispecies diversification in most cases. These findings provide a rationale to study low dose daily or pegylated interferon maintenance therapy for the management of hepatitis C posttransplant. PMID- 11213072 TI - Kidney transplantation for end-stage renal failure in liver transplant recipients with hepatitis C viral infection. AB - BACKGROUND: End-stage renal failure after successful liver transplantation (LTx) has been described in up to 5% of patients. Kidney transplantation (KTx) has been the treatment of choice in these cases. However, in recipients infected with hepatitis C virus (HCV), the augmentation of immunosuppression after KTx may result in an increased viral load. This, in turn, may adversely affect the liver allograft. METHOD: The present study retrospectively examined the outcome in 17 patients (3 females and 14 males, mean age 51.1+/-11.3 years) who received KTx after LTx. The mean interval from LTx to KTx was 57.6+/-32.1 months. The mean follow-up was 41.7+/-20.5 months after KTx, and 99.6+/-37.7 months after LTx. Sixteen of the 17 patients received tacrolimus-based immunosuppression at the time of KTx. RESULTS: During the follow-up period, one patient underwent combined liver and kidney retransplantation 3.7 years after KTx and 12.7 years after LTx. She subsequently died secondary to primary nonfunction. Four other patients died, two of lung cancer, one of pancreatitis/sepsis, and one of severe depression leading to noncompliance. A total of 29 episodes of biopsy-proven acute renal allograft rejection (1.7 episodes/ patient) were encountered and treated with steroids. Seven patients experienced a rise in liver function tests during the period of increased steroid dosage. Four patients received no treatment, and their liver function returned to baseline. The remaining three were treated with interferon. Overall 1- and 3-year actuarial patient and liver allograft survival was 88% and 71% (after renal transplantation); corresponding 1- and 3-year actuarial graft survival was 88% and 61%. Twelve patients are alive with normal liver function. One patient is on dialysis, because of renal allograft loss to noncompliance. CONCLUSION: In this series, LTx recipients with HCV infection were able to undergo KTx with a reasonable degree of success. KTx should be offered for end-stage renal failure after LTx, even in the presence of HCV infection, to individuals with stable liver function and no signs of liver failure. PMID- 11213073 TI - A worldwide, phase III, randomized, controlled, safety and efficacy study of a sirolimus/cyclosporine regimen for prevention of acute rejection in recipients of primary mismatched renal allografts. AB - BACKGROUND: Despite the various immunosuppressive regimens presently in use, acute rejection in the early postoperative period continues to occur in 20 to 40% of renal transplant patients. In a double-blind, multicentred study, we investigated the ability of two different doses of sirolimus (rapamycin, RAPAMUNE), a new class of immunosuppressant that blocks cell cycle progression, to prevent acute rejection in recipients of primary mismatched renal allografts when added to a regimen of cyclosporine (cyclosporin A, CsA) and corticosteroids. METHODS: Between October 1996 and September 1997, 576 recipients of primary mismatched cadaveric or living donor renal allografts were randomly assigned in a 2:2:1 ratio (before the transplant operation) to receive an initial loading dose of either 6 or 15 mg of orally administered sirolimus, followed by a daily dose of either 2 or 5 mg/day, or to receive a matched placebo. All groups received cyclosporine (microemulsion formula, CsA) and corticosteroids. The primary endpoint was a composite of first occurrence of biopsy-confirmed acute rejection, graft loss, or death during the first 6 months after transplantation. Safety data were monitored by an independent drug safety monitoring board. RESULTS: Based on an intention-to-treat analysis of 576 patients, there were no significant differences in patient demographic or baseline characteristics among treatment groups. The overall rate of the primary composite endpoint for the 6-month period after transplantation was 30.0% (68/227) in the 2 mg/day sirolimus group and 25.6% (56/219) in the 5 mg/day sirolimus group, significantly lower than the 47.7% (62/130) in the placebo group (P=0.002, P<0.001, respectively). During this period, the incidence of biopsy-confirmed acute rejection was 24.7% (56/227) in the 2 mg/day sirolimus group and 19.2% (42/219) in the 5 mg/day sirolimus group, compared with 41.5% (54/130) in the placebo group (P=0.003, P<0.001, respectively), representing a significant reduction in acute rejection of 40.5 and 53.7%, respectively. The need for antibody therapy to treat the first episode of biopsy-confirmed acute rejection was significantly reduced in the 5 mg/ day sirolimus group (3.2%) compared to the placebo group (8.5%; P=0.044). The results 1 year after transplantation were similar for the efficacy parameters studied. Adverse events and infections occurred in all groups. CONCLUSIONS: The addition of either 2 mg/day sirolimus or 5 mg/day sirolimus to CsA/corticosteroid therapy significantly reduces the incidence of acute rejection episodes in primary mismatched renal allograft recipients, without an increase in immunosuppressant related side effects, including infections and malignancy, at 6 months and at 1 year after transplantation. PMID- 11213074 TI - U.S. nephrologists' attitudes towards renal transplantation: results from a national survey. AB - BACKGROUND: Renal transplantation is the optimal treatment for persons with end stage renal disease (ESRD). A shortage of kidneys in the U.S. has focused increasing attention on the process by which kidneys are allocated. A national survey was undertaken to determine the relative importance of both clinical and nonclinical factors in the recommendation for renal transplantation by U.S. nephrologists. METHODS: We conducted a national random survey of 271 U.S. nephrologists using hypothetical patient scenarios to determine their recommendation for renal transplantation based on demographic, clinical, and social factors. Specifically, eight unique patient scenarios were randomly distributed to each survey respondent. RESULTS: According to responding nephrologists (response rate 53%), females were less likely than males to be recommended for renal transplantation [adjusted odds ratio (OR)=0.41; confidence interval (CI) 0.21, 0.79; for whites]. Asian males were less likely than white males to be recommended for transplantation (OR=0.46, CI 0.24, 0.91). Black-white differences in rates of recommendation were not found. Other factors associated with low rates of recommendation for renal transplantation included history of noncompliance (OR=0.17, CI 0.13, 0.23), <25% cardiac ejection fraction (OR=0.15, CI 0.10, 0.21), HIV infection (OR=0.01, CI 0.00, 0.01), and being >200 lbs (OR=0.73, CI 0.56, 0.95). CONCLUSIONS: Female gender, and Asian but not black race, were associated with a decreased likelihood that nephrologists would recommend renal transplantation for patients with end stage renal disease. The well-documented black-white disparities in use of renal transplantation may be due to unaccounted for factors or may arise at a subsequent step in the transplantation process. PMID- 11213075 TI - Fatal primary infection due to human herpesvirus 6 variant A in a renal transplant recipient. AB - We describe a fatal primary human herpesvirus 6 (HHV-6) variant A infection in a kidney transplanted adult woman. On day 20 post transplantation (TX), after rejection therapy, the patient presented an acute hemophagocytic syndrome with hepatitis and central nervous system involvement. HHV-6 IgG and IgM antibodies seroconversion was demonstrated. HHV-6 variant A was the sole pathogen detected by nested PCR and/or culture in blood, bone marrow aspiration, liver biopsy, cerebrospinal fluid and bronchoalveolar lavage. The graft was HHV-6 seropositive and the patient was not transfused before day 28 post TX, suggesting that the virus was transmitted by the graft. Despite immunoglobulins, ganciclovir and foscarnet therapy, the HHV-6 infection progressed and led to severe aplasia. The patient developed Aspergillus fumigatus pneumonia and died from fulminant candidemia. This case demonstrated for the first time that HHV-6 variant A primary infection can cause life-threatening disseminated infection in immunosuppressed patients. PMID- 11213076 TI - Transforming growth factor-beta inhibits lymphokine activated killer cytotoxicity of bone marrow cells: implications for the graft-versus-leukemia effect in irradiation allogeneic bone marrow chimeras. AB - BACKGROUND: We have previously shown that allogeneic bone marrow (BM) chimeras preconditioned with total lymphoid irradiation and low-dose total body irradiation (TLI/TBI) develop a stronger graft-versus-leukemia (GVL) effect than chimeras preconditioned with high-dose total body irradiation only (TBI). Here, we report on the possible role of cytokines in the mechanism underlying this GVL effect. METHODS: Splenic mRNA levels of the cytokines interleukin (IL)-1, IL-2, IL-4, IL-6, IL-7, IL-10, IL-12, IL-15, interferon-gamma, tumor necrosis factor alpha, and transforming growth factor-beta (TGF-beta), and of inducible nitric oxide synthetase were determined by reverse transcription-polymerase chain reaction in TLI/TBI- or TBI-conditioned C3H/AKR BM chimeras challenged with AKR type BW5147.3 leukemia cells. Ex vivo TGF-beta protein production by splenocytes was determined using ELISA. The possibility that cytokines influence the GVL effect by modulating the activity of IL-2-activated lymphocytes (LAK cells) was investigated by in vitro assays on donor-type BM cells. RESULTS: Of all cytokine mRNA levels studied, those of TGF-beta and IL-7 were different between groups; both were significantly more elevated in TBI- than in TLI/ TBI-conditioned or normal mice. Differences were apparent after conditioning and were not influenced by additionally injected BM or leukemia cells. Cultured splenocytes of TBI conditioned animals produced significantly more TGF-beta protein than those of TLI/TBI-conditioned ones or normal controls. r-TGF-beta but not r-IL-7 suppressed in vitro LAK activity of donor-type BM cells against BW5147.3 cells in a dose dependent way. CONCLUSIONS: High-dose TBI-induced, host-derived splenic TGF-beta may inhibit generation of LAK cells from subsequently transplanted donor BM cells, suppressing their capacity to generate cytotoxicity upon injection of leukemia cells. The cytokine profile, induced by irradiation in host hematopoietic organs, can significantly modify posttransplant immunological processes such as the GVL effect and graft-versus-host disease (GVHD). PMID- 11213077 TI - Lung preconditioning with N-acetyl-L-cysteine prevents reperfusion injury after liver no flow-reflow: a dose-response study. AB - BACKGROUND: Circulating xanthine oxidase activity and the generated oxidants have been linked to lung reperfusion injury from no flow-reflow conditions in other organs after organ transplantation or surgery. N-acetyl-1-cysteine (NAC), an oxidant scavenger, promotes glutathione in its reduced form (GSH) that is depleted during ischemia. We have recently demonstrated its efficacy in protecting lungs from reperfusion injury if administered during reperfusion of postischemic liver. We now investigated whether preconditioning of lungs with NAC could attenuate lung respiratory or vascular derangement after no flow-reflow (ischemia-reperfusion, IR) and if this depends on lung GSH levels. METHODS: Rat isolated livers were stabilized and perfused with modified Krebs-Henseleit solution (KH) (control, n=12) or made ischemic (no flow, IR-0, n=12) for 2 hr. Meanwhile, lungs were isolated, ventilated, and stabilized (KH+bovine albumin 5%). Serial perfusion (15 min) of liver+lung pairs took place followed by lung only recirculation (45 min) with the accumulated solution. Another three controls and three ischemic groups included lungs treated during stabilization with NAC at 100 mg x kg(-1), 150 or 225 mg x kg(-1) (in 2.5, 3.7 or 5.5 mmol solutions, respectively). Results. Ischemic liver damage, expressed by circulating hepatocellular constituents, was associated with pulmonary artery and ventilatory pressure increases by 70-100% of baseline, abnormal wet-to-dry weight ratio, and abnormal bronchoalveolar lavage volume and content in the IR-0 (nontreated) and the IR-100 and IR-225 pretreated lungs. NAC-150 pretreatment afforded preservation for most parameters. GSH content in the IR-150 lung tissue was only 11% higher than that of IR-225, but 2-fold that in IR-0 and IR-100 GSH lungs. CONCLUSION: Lung preconditioning with NAC prevents reperfusion injury but not in a dose-related manner. Although enhanced GSH tissue content explains lung protection, GSH-independent NAC activity is another possibility. PMID- 11213078 TI - Tubulitis after renal transplantation: demonstration of an association between CD103+ T cells, transforming growth factor beta1 expression and rejection grade. AB - BACKGROUND: Tubulitis is a defining feature for the diagnosis and management of acute renal allograft rejection. Lymphocytes extracted from rejecting renal tissue are known to express the alphaEbeta7-integrin (CD103), a receptor for E cadherin expressed on epithelial cells. In this study, expression of CD103 was examined in situ in tubulitis associated with acute rejection. METHODS: Immuno labeling detected CD8+ and CD103+ lymphocytes and E-cadherin on epithelial cells in cryostat sections from 34 diagnostic biopsy specimens and a limited number of transplant nephrectomies. CD8+ and CD103+ intratubular cells were enumerated as mean numbers per tubular crosssection and median values were compared between rejection grades as were median ratios of CD103+ to CD8+ cells. Active transforming growth factor (TGF) beta1 was quantified in paraffin sections by immunofluorescence and confocal microscopical analysis. A parallel in vitro study quantified CD103+ T cells after allospecific activation with and without exogenous TGFbeta1. RESULTS: CD8+ T cells were present in tubules and tubular interstitium in acute rejection. CD103+ T cells were restricted exclusively to the tubules. The numbers of intratubular CD8+ and CD103+ cells and the ratio of intratubular CD103+ to CD8+ cells increased significantly with tubulitis score (P values 0.005, 0.009, and 0.02, respectively). TGFbeta1 expression was wide-spread in tubules also increasing significantly with tubulitis score (P=0.034). In chronic rejection, CD103+ T cells and TGFbeta1 were present within both tubules and interstitial cell populations. The in vitro study demonstrated that addition of TGFbeta1 to activated, alloantigen-specific T cells increased the proportion of CD8+ cells that also expressed CD103. CONCLUSIONS: These data indicate that specific upregulation of the alphaEbeta7-integrin by activated, intratubular T cells in acute renal allograft rejection could be a consequence of exposure to high local concentrations of TGFbeta1. The capacity of CD103+ T cells to bind E cadherin on tubular epithelial cells may be an important factor in the pathogenesis of specific tissue damage observed in acute renal allograft rejection. PMID- 11213079 TI - Antigen expression in xenotransplantation: how low must it go? AB - BACKGROUND: Acute vascular rejection (AVR) is an important immunological barrier to xenotransplantation. Thought to be initiated by xenoreactive antibodies, acute vascular rejection might, in principle, be avoided by engineering animals to express low levels of antigen. The extent to which antigen expression would have to be decreased to achieve such a goal is unknown. METHODS: We estimated the decrease in expression of a xenogeneic antigen, Galalpha1-3Gal, which might be needed to avert acute vascular rejection of xenotransplants based on the decrease in antibody binding to endothelium that would prevent tissue damage. RESULTS: The level of decrease needed in Galalpha1-3Gal expression needed to avoid acute vascular rejection was estimated to exceed 96% of baseline. The extent of the decrease needed reflected, in part, a substantial "excess" of Galalpha1-3Gal on porcine endothelial cell surfaces. CONCLUSIONS: Although the change in antigen expression required to avoid acute vascular rejection might be conditioned by various factors, the very large magnitude of this change necessitates application of highly efficient approaches to antigen modification. PMID- 11213080 TI - Rat xenograft survival in mice treated with donor-specific transfusion and anti CD154 antibody is enhanced by elimination of host CD4+ cells. AB - BACKGROUND: Treatment with a donor-specific transfusion (DST) and a brief course of anti-mouse CD154 (anti-CD40-ligand) monoclonal antibody (mAb) prolongs the survival of both allografts and rat xenografts in mice. The mechanism by which allograft survival is prolonged is incompletely understood, but depends in part on the presence of CD4+ cells and the deletion of alloreactive CD8+ T cells. Less is known about the mechanism by which this protocol prolongs xenograft survival. METHODS: We measured rat islet and skin xenograft survival in euthymic and thymectomized mice treated with combinations of DST, anti-CD154 mAb, anti-CD4 mAb, and anti-CD8 mAb. Recipients included C57BL/6, C57BL/6-scid, C57BL/6 CD4null, and C57BL/6-CD8null mice. RESULTS: Pretreatment with a depleting anti CD4 mAb markedly prolonged the survival of both skin and islet xenografts in mice given DST plus anti-CD154 mAb. Comparable prolongation of xenograft survival was obtained in C57BL/6-CD4null recipients treated with DST and anti-CD154 mAb. In contrast, anti-CD8 mAb did not prolong the survival of either islet or skin xenografts in mice treated with DST and anti-CD154 mAb. Thymectomy did not influence xenograft survival in any treatment group. Adoptive transfer of splenocytes from C57BL/6-CD4null recipients treated with DST and anti-CD154 mAb and bearing long-term skin xenografts revealed the presence of residual xenoreactive cells. CONCLUSIONS: These data suggest that treatment with DST and anti-CD154 mAb induces a state of "functional" transplantation tolerance. They also support the hypothesis that both the induction and maintenance of graft survival based on this protocol depend on different cellular mechanisms in allogeneic and xenogeneic model systems. PMID- 11213081 TI - Simplified technique of orthotopic liver transplantation in pigs. AB - BACKGROUND: Pig models have become common in transplantation immunological research. However, in pigs, clamping of the venous splanchnic system during orthotopic liver transplantation (OLT) is responsible for high morbidity and mortality rates; therefore, the use of venovenous bypass (VVB) is advocated. Because venous bypass can also cause specific complications, a simplified method for OLT in pigs has been developed and evaluated in terms of morbidity and mortality. METHODS: Twenty-three OLTs were performed between pairs of inbred miniature swine. Donor and recipient pairs (weighing 20-35 kg) were selected at 3 6 months of age. In the donor, the portal vein, infrahepatic vena cava, and suprahepatic vena cava were dissected, whereas the hepatic artery was preserved in continuity with the coeliac trunk and the abdominal aorta up to the iliac bifurcation. In situ cold perfusion was then performed. The recipient was prepared simultaneously by another surgical team. After total hepatectomy and complete portal and caval clamping, the suprahepatic vena cava and portal vein were sutured; VVB was not used. After completion of both venous sutures, the liver graft was reperfused. The infrahepatic vena cava was then anastomosed and unclamped. The donor aorta conduit was implanted end-to-side to the recipient infrarenal aorta, and the biliary reconstruction consisted of a cholecystojejunostomy with a Roux-Y loop. RESULTS: Twenty of 23 (87%) animals survived more than 1 week (7-483 days). The mean anhepatic time was 29.6+/-4.12 min. Although severe hypotension was noted during the anhepatic phase, the hemodynamic status rapidly recovered and stabilized after graft reperfusion. CONCLUSION: Simplified technique without VVB is appropriate for successfully achieving OLT in pigs. PMID- 11213082 TI - Vitamin E inhibits renal mRNA expression of COX II, HO I, TGFbeta, and osteopontin in the rat model of cyclosporine nephrotoxicity. AB - BACKGROUND: In a rat model of cyclosporine (CsA) nephrotoxicity, vitamin E preserves renal function and reduces free radicals, vasoconstrictive thromboxanes, and tubulointerstitial fibrosis. We examined the effect of vitamin E on tubule gene expression in this model. METHODS: In two of three groups, rats were treated with either CsA, or CsA plus vitamin E, whereas the control group received vehicles. We pooled purified tubules or whole kidney tissue in a novel manner to represent each treatment group, harvested RNA, and performed rigorously controlled qualitative reverse transcription-polymerase chain reaction. RESULTS: Cyclooxygenase (COX) I mRNA was detectable in control animals, was increased by CsA, but was unchanged by vitamin E. COX II mRNA was detected in controls, was inhibited in the CsA group, and was further inhibited with vitamin E. Hemeoxygenase I and TGF-beta and osteopontin mRNA were increased in the CsA treated group and were inhibited by vitamin E. CONCLUSIONS: Our data support the involvement of free radicals, COX pathways, and pro-fibrotic genes in cyclosporine nephrotoxicity and suggest that the salutary effect of vitamin E involves the suppression of some of these genes. PMID- 11213083 TI - Chronic diarrhea as a result of intestinal microsposidiosis in a liver transplant recipient. AB - BACKGROUND: Microsporidia are common pathogens among patients infected with human immunodeficiency virus. They account for a substantial proportion of chronic diarrhea and malabsorption in acquired immune deficiency syndrome, but their appearance after solid organ transplantation has only rarely been reported. Methods. We report what we believe is the first case of documented Enterocytozoon bieneusi infection in a liver transplant recipient. Results. Our patient presented with chronic diarrhea and colicky abdominal pain. Although symptoms were severe, only mild microscopical mucosal changes were found in the intestinal tract. A modified trichrome stain of stool specimens revealed microsporidial spores, and species differentiation by restriction fragment length polymorphism polymerase chain reaction identified Enterocytozoon bieneusi. Albendazole therapy brought symptomatic relief but no microbiological clearance. CONCLUSIONS: Enterocytozoon bieneusi may cause chronic diarrhea not only in immunosuppression as a result of human immunodeficiency virus infection but also among patients with therapeutic immunosuppression after organ transplantation. Therefore, microsporidial infection should be considered in immunosuppressed patients with otherwise unexplained diarrhea. PMID- 11213084 TI - Primary fibroblast cell cultures from transbronchial biopsies of lung transplant recipients. AB - BACKGROUND: Survival after lung transplantation is limited by the development of bronchiolitis obliterans (BO) that is a fibroproliferative process and regarded as the histological marker of chronic rejection. To study further the pathogenesis of BO we attempted to establish primary fibroblast cell cultures from transbronchial lung biopsies (TBBs)of lung transplant recipients. METHODS: One to two TBB samples from each patient were collected in sterile phosphate buffered saline. Biopsies were cut into small pieces and placed onto 25-cm2 culture flasks for cell culture and kept under standard cell culture conditions (21% O2, 5% CO2, 37 degrees C). Culture medium consisted of RPMI 1640, 10% fetal calf serum, L-glutamine, HEPES, and antibiotics. After reaching confluence, fibroblasts were passaged into 75-cm2 flasks. RESULTS: The success rate of establishing fibroblast cultures from transbronchial lung biopsies was 54% (27/50). Cell growth was independent of patient age, transplant type, underlying lung disease, indication for transbronchial lung biopsies, grade, or type of re jection and infection. CONCLUSIONS: We have established a novel method of culturing fibroblasts from lung transplant recipients. We consider this method as an unique human in vitro model to study the pathogenetic mechanisms leading to BO. PMID- 11213085 TI - Retention of organs after necropsy. PMID- 11213086 TI - Role of antibody response in outcome of antibiotic-associated diarrhoea. PMID- 11213087 TI - Prospects for improving staging of ovarian cancers. PMID- 11213088 TI - Anticipation of epileptic seizures from standard electro-encephalographic recordings. PMID- 11213089 TI - Regulation of the cholesterol efflux gene, ABCA1. PMID- 11213090 TI - Effects of volcanic air pollution on health. PMID- 11213091 TI - Review of first 5 years of screening for familial hypercholesterolaemia in the Netherlands. AB - BACKGROUND: Familial hypercholesterolaemia is a common lipid disorder that predisposes for premature cardiovascular disease (CVD). We set up a screening programme in the Netherlands in 1994 to: establish the feasibility of active family screening supported by DNA diagnostics; assess whether or not active identification of these patients with familial hypercholesterolaemia would lead to more cholesterol-lowering treatment; and compare diagnosis by DNA analysis with that by cholesterol measurement. METHODS: Both DNA analysis and measurement of cholesterol concentrations were used to screen families in which a functional mutation in the LDL-receptor gene had been detected. FINDINGS: In the first 5 years, 5442 relatives of 237 people with familial hypercholesterolaemia were screened; 2039 individuals were identified as heterozygous by LDL-receptor gene mutation analysis. At the time of examination, 667 of these adults with familial hypercholesterolaemia (39%) received some form of lipid-lowering treatment; 1 year later, this percentage had increased to 93%. In addition, laboratory analysis showed that for carriers as well as non-carriers 18% would have been misdiagnosed by cholesterol measurement alone, with sex-specific and age-specific 90th percentiles of the general Dutch population as diagnostic criteria. INTERPRETATION: Targeted family screening with DNA analysis proved to be highly effective in identifying patients with hypercholesterolaemia. Most of the identified patients sought treatment and were successfully started on cholesterol lowering treatment to lower the risk of premature CVD. Our findings could have wider relevance for the screening of other prevalent genetic disorders in the population at large. PMID- 11213092 TI - Clinical picture: paravertebral abscess. PMID- 11213093 TI - Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales. Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS). AB - BACKGROUND: We have undertaken a large unselected, community-based neuropathology study in an elderly (70-103 years) UK population in relation to prospectively evaluated dementia status. The study tests the assumption that dementing disorders as defined by current diagnostic protocols underlie this syndrome in the community at large. METHODS: Respondents in the Medical Research Council Cognitive Function and Ageing Study were approached for consent to examine the brain at necropsy. Dementia status was assigned by use of the automated geriatric examination for computer-assisted taxonomy algorithm. Neuropathological features were standardised by use of the protocol of the Consortium to Establish a Registry of Alzheimer's Disease, which assesses the severity and distribution of Alzheimer-type pathology, vascular lesions, and other potential causes of dementia. A statistical model of dementia risk related predominantly to Alzheimer type and vascular pathology was developed by multivariate logistic regression. FINDINGS: We report on the first 209 individuals who have come to necropsy. The median age at death was 85 years for men, and 86 years for women. Cerebrovascular (78%) and Alzheimer-type (70%) pathology were common. Dementia was present in 100 (48%), of whom 64% had features indicating probable or definite Alzheimer's disease. However, 33% of the 109 non-demented people had equivalent densities of neocortical neuritic plaques. Some degree of neocortical neurofibrillary pathology was found in 61% of demented and 34% of non-demented individuals. Vascular lesions were equally common in both groups, although the proportion with multiple vascular pathology was higher in the demented group (46% vs 33%). INTERPRETATION: Alzheimer-type and vascular pathology were the major pathological correlates of cognitive decline in this elderly sample, as expected, but most patients had mixed disease. There were no clear thresholds of these features that predicted dementia status. The findings therefore challenge conventional dementia diagnostic criteria in this setting. Additional factors must determine whether moderate burdens of cerebral Alzheimer-type pathology and vascular lesions are associated with cognitive failure. PMID- 11213094 TI - Prognostic importance of degree of differentiation and cyst rupture in stage I invasive epithelial ovarian carcinoma. AB - BACKGROUND: Previous studies on prognostic factors in stage I invasive epithelial ovarian carcinoma have been too small for robust conclusions to be reached. We undertook a retrospective study in a large international database to identify the most important prognostic variables. METHODS: 1545 patients with invasive epithelial ovarian cancer (International Federation of Gynaecology and Obstetrics [FIGO] stage I) were included. The records of these patients were examined and data extracted for univariate and multivariate analysis of disease-free survival in relation to various clinical and pathological variables. FINDINGS: The multivariate analyses identified degree of differentiation as the most powerful prognostic indicator of disease-free survival (moderately vs well differentiated hazard ratio 3.13 [95% CI 1.68-5.85], poorly vs well differentiated 8.89 [4.96 15.9]), followed by rupture before surgery (2.65 [1.53-4.56]), rupture during surgery (1.64 [1.07-2.51]), FIGO 1973 stage Ib vs Ia 1.70 [1.01-2.85]) and age (per year 1.02 [1.00-1.03]). When the effects of these factors were accounted for, none of the following were of prognostic value: histological type, dense adhesions, extracapsular growth, ascites, FIGO stage 1988, and size of tumour. INTERPRETATION: Degree of differentiation, the most powerful prognostic indicator in stage I ovarian cancer, should be used in decisions on therapy in clinical practice and in the FIGO classification of stage I ovarian cancer. Rupture should be avoided during primary surgery of malignant ovarian tumours confined to the ovaries. PMID- 11213095 TI - Anticipation of epileptic seizures from standard EEG recordings. AB - BACKGROUND: New methods derived from non-linear analysis of intracranial recordings permit the anticipation of an epileptic seizure several minutes before the seizure. Nevertheless, anticipation of seizures based on standard scalp electroencephalographical (EEG) signals has not been reported yet. The accessibility to preictal changes from standard EEGs is essential for expanding the clinical applicability of these methods. METHODS: We analysed 26 scalp EEG/video recordings, from 60 min before a seizure, in 23 patients with temporal lobe epilepsy. For five patients, simultaneous scalp and intracranial EEG recordings were assessed. Long-term changes before seizure onset were identified by a measure of non-linear similarity, which is very robust in spite of large artifacts and runs in real-time. FINDINGS: In 25 of 26 recordings, measurement of non-linear changes in EEG signals allowed the anticipation of a seizure several minutes before it occurred (mean 7 min). These preictal changes in the scalp EEG correspond well with concurrent changes in depth recordings. INTERPRETATION: Scalp-EEG recordings retain sufficient dynamical information which can be used for the analysis of preictal changes leading to seizures. Seizure anticipation strategies in real-time can now be envisaged for diverse clinical applications, such as devices for patient warning, for efficacy of ictal-single photon emission computed tomography procedures, and eventual treatment interventions for preventing seizures. PMID- 11213096 TI - Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea. AB - BACKGROUND: We have reported that symptom-free carriers of Clostridium difficile have a systemic anamnestic immune response to toxin A. The aim of this study was to determine whether an acquired immune response to toxin A, during an episode of C. difficile diarrhoea, influences risk of recurrence. METHODS: We prospectively studied 63 patients with nosocomial C. difficile diarrhoea. Serial serum IgA, IgG, and IgM concentrations against C. difficile toxin A, toxin B, or non-toxin antigens were measured by ELISA. Individuals were followed for 60 days. FINDINGS: 19 patients died (30%). Of the 44 who survived, 22 had recurrent C. difficile diarrhoea. Patients with a single episode of C. difficile diarrhoea (n=22) had higher concentrations of serum IgM against toxin A on day 3 of their first episode of diarrhoea than those with recurrent diarrhoea (n=22, p=0.004). On day 12, serum IgG values against toxin A were higher in patients who had a single episode of diarrhoea (n=7) than in those who subsequently had recurrent diarrhoea (n=9, p=0.009). The odds ratio for recurrence associated with a low concentration of serum IgG against toxin A, measured 12 days after onset of C. difficile diarrhoea, was 48.0 (95% CI 3.5-663). INTERPRETATION: A serum antibody response to toxin A, during an initial episode of C. difficile diarrhoea, is associated with protection against recurrence. PMID- 11213097 TI - Emphysematous pyelonephritis: a rare cause of pneumaturia. PMID- 11213098 TI - Efficacy of meningococcal serogroup C conjugate vaccine in teenagers and toddlers in England. AB - The UK was the first country to use meningococcal serogroup C conjugate (MCC) vaccines, which were licensed on the basis of immunogenicity and safety data but without a formal efficacy study. Increased surveillance during the first 9 months since introduction has shown that short-term efficacy of the MCC vaccine in England was 97% (95% CI 77-99) for teenagers and 92% (65-98) for toddlers. These early results confirm the superiority of MCC over plain C polysaccharide vaccines, which are ineffective in young children. PMID- 11213099 TI - Prevention of hepatocellular carcinoma in patients with chronic active hepatitis C and cirrhosis. AB - In a prospective randomised controlled study, 90 patients with chronic active hepatitis C and compensated cirrhosis were assigned symptomatic treatment or interferon alfa (IFN-alpha). We report data on decompensation, detection of hepatocellular carcinoma, and mortality rates. IFN-alpha gave a sustained response in only a small proportion of patients, but worsening of compensated cirrhosis was prevented and development of hepatocellular carcinoma was inhibited, increasing the survival rate. The risk ratio of IFN-alpha versus symptomatic treatment decreased by 0.250 for progression to Child-Pugh grade B, 0.256 for detection of hepatocellular carcinoma, and 0.135 for a fatal outcome. PMID- 11213101 TI - Eclipse burns: a prospective study of solar retinopathy following the 1999 solar eclipse. AB - Looking at the sun can cause focal burns to the retina. We prospectively followed up all patients who presented to Eye Casualty of Leicester Royal Infirmary having observed the solar eclipse of August, 1999. 45 patients attended, of whom 20 had visual symptoms and five had visible changes in the retina; four patients were still symptomatic after 7 months. PMID- 11213100 TI - The evolution of human group B rotaviruses. AB - The largest reported rotavirus epidemic affected well over a million people in China during 1982-83 and was caused by the adult diarrhoea rotavirus (ADRV), a serogroup B rotavirus. However, ADRV has not been reported outside China since the last recorded small outbreak there in 1987. Here we present evidence that offers an explanation for the sudden appearance and disappearance of the epidemic ADRV strain. PMID- 11213102 TI - NATO doctors question "Balkan war syndrome". PMID- 11213103 TI - New vaccines for mycobacterial infections "desperately needed". PMID- 11213104 TI - Making new connections--preventing the brain drain. PMID- 11213105 TI - Good health news spares UK government from media onslaught. PMID- 11213106 TI - Child activist's critical condition is wake-up call for nation. PMID- 11213107 TI - Family-practice doctors seek to reawaken US health-care debate. PMID- 11213108 TI - Germany's Health and Agriculture ministers resign over handling of BSE. PMID- 11213109 TI - UN sanctions imposed against Afghanistan while thousands flee. PMID- 11213110 TI - Primary, secondary, and tertiary prevention of pre-eclampsia. AB - Pre-eclampsia remains one of the major obstetrical problems in less-developed countries. The causes of this condition are still unknown, thus effective primary prevention is not possible at this stage. Research in the past decade has identified some major risk factors for pre-eclampsia, and manipulation of these factors might result in a decrease in its frequency. In the early 1990s aspirin was thought to be the wonder drug in secondary prevention of pre-eclampsia. Results of large trials have shown that this is not the case: if there is an indication for using aspirin it is in the patient at a very high risk of developing severe early-onset disease. The calcium story followed a more or less similar pattern, with the difference that existing evidence shows that women with a low dietary calcium intake are likely to benefit from calcium supplementation. Proper antenatal care and timed delivery are of utmost importance in tertiary prevention of pre-eclampsia. There is evidence to suggest that the intrinsic direct effect of moderate degrees of maternal hypertension is beneficial to the fetus. Severe hypertension needs treatment. If antihypertensive is indicated, there is no clear choice of a drug. Hydralazine should no longer be thought of as the primary drug, most studies show a preference for calcium channel blockers. PMID- 11213111 TI - Neuropsychological effects of epilepsy and antiepileptic drugs. AB - Epilepsy and its treatment can have deleterious cognitive and behavioural consequences. Affected individuals have a higher prevalence of neuropsychological dysfunction than the general population because of complex interactions among several multifaceted and overlapping influences--for example, underlying neuropathologies, ictal and interictal neuronal discharges, a plethora of antiepileptic drugs, and numerous psychosocial issues. Research into the clinical relevance of these factors has been dogged by a range of methodological pitfalls including lack of standardisation of neuropsychological tests, small numbers and multiple testing, and statistical failure to appreciate differential effects of interactive elements in individual patients. Although antiepileptic drugs can impair neuropsychological functioning, their positive effect on seizure control might improve cognition and behaviour. Each person should be assessed individually with respect to factors unique to his or her seizure disorder and its treatment. PMID- 11213112 TI - What can be achieved with an HIV vaccine? PMID- 11213113 TI - Term breech trial. PMID- 11213114 TI - Term breech trial. PMID- 11213115 TI - Term breech trial. PMID- 11213116 TI - Term breech trial. PMID- 11213117 TI - Term breech trial. PMID- 11213118 TI - Term breech trial. PMID- 11213119 TI - Term breech trial. PMID- 11213120 TI - Term breech trial. PMID- 11213121 TI - Syndrome X in testicular-cancer survivors. PMID- 11213122 TI - Follicle-stimulating-hormone receptor and twinning. PMID- 11213123 TI - Follicle-stimulating-hormone receptor and twinning. PMID- 11213124 TI - Follicle-stimulating-hormone receptor and twinning. PMID- 11213125 TI - HIV-1 infection and malaria parasitaemia. PMID- 11213126 TI - HIV-1 infection and malaria parasitaemia. PMID- 11213127 TI - HIV-1 infection and malaria parasitaemia. PMID- 11213128 TI - Heparin and aspirin in stroke. PMID- 11213129 TI - The gender gap in autoimmune disease. PMID- 11213130 TI - Wound botulism in the UK. PMID- 11213131 TI - African malaria vectors in European aircraft. PMID- 11213133 TI - Drug development for tuberculosis: the missing ingredient. PMID- 11213132 TI - African malaria vectors in European aircraft. PMID- 11213134 TI - Declaration of Helsinki. PMID- 11213135 TI - Tip-of-the-tongue experiences. PMID- 11213136 TI - A clinical trial. PMID- 11213137 TI - Sourdough, homoeopathy, and evidence-based medicine. PMID- 11213138 TI - A relative risk-based, disease-specific definition of sexual abstinence failure rates. AB - Sexual abstinence programs have the potential to reduce the incidence of unplanned pregnancies and sexually transmitted diseases (STDs) among adolescents. Effectiveness measures are needed to help researchers assess the impact of sexual abstinence promotion programs on STD and pregnancy rates and to enable comparisons of abstinence effectiveness with other contraception and STD prevention methods. Abstinence "failure rates" have been proposed as one measure of program effectiveness. However, the concept of abstinence failure rates has not been adequately operationalized. The present study examines a novel mathematical framework for estimating abstinence failure rates, both theoretically and empirically. Examples are provided, and the advantages and disadvantages associated with the mathematical model-based approach are discussed. PMID- 11213139 TI - Disease-specific sexual abstinence user rates: the role of science in policy making. PMID- 11213140 TI - Factors associated with Army obstetricians-gynecologists' practice of HIV prevention education during routine gynecologic care. AB - The authors evaluate obstetricians-gynecologists' (OB-GYNs') anxiety about clinical uncertainty and patient, physician, and organizational factors associated with their selection of HIV-related educational activities for high risk and low-risk written case simulations. A total of 117 U.S. Army OB-GYNs completed a mailed, anonymous questionnaire. Overall, informants were much less likely to educate in response to the low-risk simulation; however, more informants who were anxious about uncertainty were more likely to do so in a model that included supportive institutional policies, willingness to educate despite patient barriers, and comfort with the topic. OB-GYNs were more likely to educate in response to the high-risk simulation given greater willingness to discuss HIV despite organizational barriers, supportive policies, and comfort. Findings suggest a need to better understand the role that anxiety about uncertainty plays in HIV prevention and the need to promote organizational policies that support and remove barriers to clinically based education. PMID- 11213141 TI - Sources influencing patients in their HIV medication decisions. AB - The authors surveyed 202 patients (54.5% male; 62.4% African American) enrolled at St. Louis HIV clinics to identify the importance of various sources of influence in their HIV medication decisions. Physicians were the most important source for 122 (60.4%) respondents, whereas prayer was most important for 24 respondents (11.9%). In multivariate tests controlling for CD4 counts, Caucasian men were more likely than Caucasian women and African Americans of both genders to select a physician as the most important source. African Americans were more likely than Caucasians to mention prayer as the most important source. Caucasians and those rating physicians as the most important source were more likely to be using antiretroviral medications. Respondents identified multiple important influences-hence the potential for conflicting messages about HIV medications. These findings have implications for health education practices and behavioral research in the medical setting. PMID- 11213143 TI - Hispanic cultural norms for health-seeking behaviors in the face of symptoms. AB - This study examines factors that contribute to the delayed use of medical care among Hispanics when chronic disease-related symptoms (warning signs) occur. As an adjunct to a larger project funded by the National Cancer Institute, this study accessed a population of primarily Hispanic, mostly male employees at public work sites in two Arizona counties. Through focus groups and a survey of employees, a model describing the factors underlying health care use was tested. Seriousness of symptoms has the most effect on visits to doctor, with more serious symptoms leading to prompter visits. Faith in God and seriousness of symptoms both are related to the search for a doctor one can trust. Also, a cluster of variables describing past bad experiences, practical barriers, and emotional avoidance are related to the desire to get advice or medical help from someone who is close; these influence the search for a trusted doctor, which in turn leads to prompter visits to doctor. PMID- 11213142 TI - Selected ethical issues in research and publication: perceptions of health education faculty. AB - A national random sample of 195 university health education faculty at graduate degree-granting programs completed a 31-item survey with regard to their perceptions of ethical issues in research and publishing. Most respondents were male (57%), tenured (75%), had graduate faculty status (92%), had presented original research at conferences (85%), and had published articles in health education journals (89%). Faculty members were requested to assess whether 21 scenarios dealing with ethical issues in research and publishing were ethical, unethical, questionable, or not an ethical issue. Of the scenarios, 3 were considered ethical and 7 unethical by the majority of respondents. The perceptions of how ethical the remaining 11 scenarios were varied considerably. Perceptions of the ethical scenarios did not differ among respondents by sex, academic rank, years taught as a faculty member, whether the department taught units/classes on research ethics, or whether the respondents were from doctoral level versus master's-level programs. PMID- 11213144 TI - When the perpetrator gets killed: effects of observing the death of a handgun user in a televised public service announcement. AB - This study evaluates the cognitive effects of an anti-handgun violence public service announcement (PSA) on sixth-, seventh-, and eighth-grade students (N = 294). Participants were randomly assigned to a treatment group, which viewed a PSA depicting the death of an aggressive handgun user, or a comparison group, which viewed identical content except that the PSA showed no negative consequence for the handgun user. Logistic regression analysis, adjusting for race and gender, revealed that the treatment group was more likely to report negative expected outcomes for aggressively using a handgun and lower behavioral intentions to aggressively use a handgun compared with the comparison group. These findings suggest that observing handgun violence on television that depicts death as a negative physical consequence for the perpetrator may produce lower handgun-encouraging beliefs compared with observing no consequence for the perpetrator--the norm for most televised violence today. PMID- 11213145 TI - Peer and parent influences on smoking and drinking among early adolescents. AB - Social influences can promote or discourage adolescent substance use. The authors surveyed 4,263 sixth- to eighth-grade students to assess the effect of peer and parent influences on adolescent substance use. The authors conducted separate multiple logistic regression analyses for smoking and drinking, controlling for grade, sex, and race. Positive independent associations with smoking and drinking were found for direct peer pressure and associating with problem-behaving friends. Independent negative associations with smoking and drinking were also found for parent involvement, parent expectations, and parent regard. In an analysis of interactions, peer pressure was positively associated with drinking for girls but not for boys and problem-behaving friends was positively associated with drinking for both boys and girls. The findings are consistent with the hypothesis that associating with deviant peers promotes and that authoritative parenting protects against smoking and drinking. PMID- 11213146 TI - Hydatid disease--continuing serious public health problem: introduction. PMID- 11213147 TI - Laboratory diagnosis of cystic hydatic disease. AB - The main purpose of this article is to answer the questions about which test to perform for hydatic diagnosis and when. Several techniques for biologic diagnosis and follow-up of human cystic hydatidosis are reviewed. The specificity and sensitivity of immunologic reactions are reported. The differential diagnosis between Echinococcus granulosus and E. multilocularis is examined. The characteristics of the immunologic diagnosis according to the stage and the treatment of hydatidosis disease is discussed. Laboratory diagnosis of cystic hydatic disease is complementary to the clinical data. A judicious association of the usual techniques (indirect immunofluorescence assay, indirect hemagglutination assay, immunoelectrophoresis, co-electrophoresis with antigen 5 identification) confirms the diagnosis in 80% to 94% of hepatic hydatidosis cases and in 65% of pulmonary hydatidosis cases. Special techniques (enzyme-linked immunosorbent assay, Western blot, polymerase chain reaction) must be used for other localizations or when cysts are calcified. A serologic survey is necessary for the follow-up of operated medically treated patients. Despite poor standardization, purified antigens can distinguish between E. granulosus and E. multilocularis infections, although false-positive results are observed during other helminthiases, such as cysticerocosis. PMID- 11213148 TI - Fiberoptic bronchoscopy of intubated patients with life-threatening hemoptysis. AB - Bleeding in the tracheobronchial tree in intubated patients on an intensive care unit is a potentially life-threatening incident. The antecedent state of disease and frequent respiratory failure require immediate and effective therapeutic measures to avoid further respiratory and cardiocirculatory depression. We present our bronchoscopic management of endobronchial bleeding. Cardiorespiratory function must be maintained by modification of the mechanical ventilation and drug therapy owing to the patient's condition. Seven consecutive patients with acute endobronchial bleeding were treated with fiberoptic bronchoscopy and instillation of cold epinephrine-saline solution (1:10,000-100,000) during the period of July 1997 to December 1997. Control of bleeding was achieved after 1 to 20 (mean +/- SEM: 5.86 +/- 0.93) bronchoscopic interventions during a period of 0.5 hours to 10 days. One control bronchoscopy was performed additionally in every patient. Cardiocirculatory instability was observed in five patients. Six patients survived; one patient died of uncontrolled bleeding caused by severe pulmonary aspergillosis. Fiberoptic endobronchial epinephrine instillation is an effective therapy for life-threatening hemoptysis in critically ill patients. Widespread use of flexible bronchoscopy makes this procedure immediately applicable in critical situations. Intubated and mechanically ventilated patients with life-threatening hemoptysis especially benefit from this rapidly feasible procedure. PMID- 11213149 TI - Determining which patients require evaluation for blunt cardiac injury following blunt chest trauma. AB - The objective of this study was to determine prospectively which risk factors require cardiac monitoring for blunt cardiac injury (BCI) following blunt chest trauma. All patients who sustained blunt chest trauma had an electrocardiogram (ECG) on admission to our urban level I trauma center. Those with ST segment changes, dysrhythmias, hemodynamic instability, history of cardiac disease, age > 55 years, or a need for general anesthesia within 24 hours (group 1) were admitted to the intensive care unit (ICU) for 24 hours where they were subjected to serial ECGs, creatinine phosphokinase (CPK) assays, and echocardiography (ECHO). Those with only mechanism for BCI, i.e., none of the above risk factors (group 2), were admitted to a nonmonitored bed and had a follow-up ECG 24 hours later. A series of 315 patients were admitted with blunt chest trauma during a 17 month period; 144 patients were in group 1 and 171 in group 2. Overall, 22 patients were diagnosed as BCI (+BCI), defined as evolving ST segment changes, dysrhythmias, a CPK-MB index of > 2.5, or hemodynamic instability. Of the 18 +BCI patients in group 1, all were symptomatic (i.e., none was included solely for a cardiac history, age, or need for general anesthesia). Six of these patients required treatment for dysrhythmias, hypotension, or pulmonary edema; one of whom died. Four patients with +BCI were in group 2 and had ECG changes at 24 hours; none of these four had any sequelae from their +BCI. None of the ECHOs demonstrated abnormal wall motion. Patients who sustain blunt chest trauma with a normal ECG, normal blood pressure, and no dysrhythmias on admission require no further intervention for BCI. Patients with ST segment changes, dysrhythmias, or hypotension following blunt chest trauma should be monitored for 24 hours, as this subgroup occasionally requires further treatment for complications of BCI. ECHO adds nothing as a screening test. PMID- 11213150 TI - Teaching hospital perspective of the quality of trauma care in Lagos, Nigeria. AB - Information including respiratory rate, blood pressure, Glasgow Coma Scale, and anatomic injuries were obtained for all injured patients consecutively admitted to the Lagos University Teaching Hospital (LUTH) during the 9-month period from September 1995 to May 1996. The data were analyzed using the UK Major Trauma Outcome Study (MTOS) methodology. The Revised Trauma Score (RTS), the Injury Severity Score (ISS), and the Probability of Survival (Ps) were calculated for each patient. In addition, the "M," "z," and "w" scores were calculated for blunt injuries. Of the 253 patients (median age 28 years; male/female ratio 4:1) studied, 85% suffered blunt trauma, 75% of which were due to RTA. About 60% of RTA victims were pedestrians. Only 8% of nonpedestrian victims wore protective devices. The mean ISS was 10, the mean RTS 6.98, and the mean Ps 0.96. The "m" statistic for blunt trauma was 0.91, and there were 122 survivors compared to the 163 predicted. The "z" and "w" scores were -18.49 and -24.55, respectively. Altogether, 42.7% of patients with ISS > 15 and 40.7% with RTS < 7.5 died. According to these results, the severity of injuries encountered in Lagos is comparable to those reported from the United Kingdom and the United States, but the death rate is higher. PMID- 11213151 TI - Medical treatment of liver hydatidosis. AB - There are currently three treatment options for liver hydatidosis: urgery, which remains the mainstay of radical treatment; ultrasound-guided aspiration (puncture/aspiration/injection/reaspiration--PAIR); and chemotherapy with benzimidazole compounds (albendazole and mebendazole). Chemotherapy is a noninvasive treatment and is less limited by the patient's status than surgery or PAIR but is not ideal when used alone. Albendazole, the drug most often used, appears to have the greatest efficacy of any agent used so far; nevertheless, apparent cure (shrinkage or disappearance of cysts) ranges only between 20% and 30% of cases. The possible contribution of perioperative chemotherapy offers the prospect of preventing recurrent disease, but it requires more clinical trials to establish that pre- or postoperative chemotherapy does prevent recurrence. The main adverse events are related to changes in liver enzyme levels and bone marrow suppression. About 10% to 20% of patients develop self-limited, reversible rises in transaminase levels; clinically severe pancytopenia or agranulocytosis is exceptional. Alopecia is observed during long-term treatment with albendazole. In all cases these events disappear once treatment is interrupted. According to the World Health Organization guidelines, chemotherapy is the preferred treatment when the disease is inoperable, when surgery or PAIR is not available, or when the cysts are too numerous. Another important indication for chemotherapy is the prevention of secondary echinococcosis. There is not yet formal consensus, as the efficacy and safety of some of the methods require further evaluation before we can establish comprehensive guidelines for the medical treatment of hydatidosis. PMID- 11213152 TI - Diagnosis and treatment of uncomplicated hydatid cyst of the liver. AB - Hydatid disease of the liver is still endemic in certain parts of the world. The diagnosis of noncomplicated hydatid cyst of the liver depends on clinical suspicion. Ultrasonography and computed tomography, the most important diagnostic tools, are helpful for determining the complications and planning treatment. The modern treatment of hydatid cyst of the liver varies from surgical intervention to percutaneous drainage or medical therapy. Surgery is still the treatment of choice and can be performed by the conventional or laparoscopic approach. Percutaneous drainage and treatment of the cyst with hypertonic saline or alcohol seems to be a good alternative to surgery in selected cases. Currently, we treat types I and II by ultrasound-guided percutaneous drainage and types IV and V (excluding totally calcified cysts) surgically. Type III cysts can be managed either way depending on the presence of drainable content. We believe that the laparoscopic approach should be limited to noncomplicated cysts. PMID- 11213153 TI - Management of liver hydatid cysts with a large biliocystic fistula: multicenter retrospective study. Tunisian Surgical Association. AB - The large biliocystic fistula (> 5 mm) encountered with hydatic cyst of the liver produces clinical manifestations only when it allows the hydatic cyst content to pass into the common bile duct. Various therapeutic problems occur. The aim of this study was to evaluate the results of the therapeutic methods used by 14 Tunisian centers to treat this specific aspect of the hydatic cyst of the liver associated with a large biliocystic fistula. This study concerned a period of 5 years between January 1988 and December 1992, and it included 244 cases associated with hydatic content in the common bile duct (158 cases) and with cholelithiasis and choledocholithiasis (2 cases); 127 patients underwent an emergency operation (52%). The surgical procedures performed consisted in radical procedures (24 cases, 9.8%) and conservative procedures (220 cases, 90.2%). The latter included 52 cases of internal transfistulary drainage, 140 unroofing procedures associated in 20 cases with the fistula, in 93 cases with suture of the fistula, and in 27 cases with direct fistulization. In the 28 remaining cases, through the choledoctomy evacuation of the parasite was performed. The common bile duct was approached in 180 cases (73.7%). The postoperative course was uneventful in 57% of the cases and complicated in 38.5% others. The mortality rate was 4.5%. In conclusion, the presence (or not) of hydatic material in the common bile duct did not seem to be a determinant of the surgical procedure choice and did not influence the results. The only difficulty with treatment was the large biliocystic fistula itself. The internal transfistulary drainage on one part, and the unroofing procedure associated with suturing healthy fistula tissue and to omentoplasty or capitonnage of the remaining cavity on the other part, were easily performed and constituted efficient methods. Radical methods constituted operations that had excellent results, but they were feasible in only 10% of the cases. PMID- 11213154 TI - Hydatidosis: dynamics of transmission. AB - Hydatidosis is a widespread zoonosis infecting a large number of animals and humans. Echinococcus granulosus has the smallest taenia adult of the cestodes but with the largest larva. Its morphologic and biologic features were identified with DNA analysis. Different strains were separated according to the intermediate hosts: sheep, cattle, pigs, horses, camels. Definitive host are canids, mostly dogs, where the worm grows to adulthood in several months. The eggs are scattered in the pasture by wind and water and are ingested by various hosts. The larvae migrate through the intestinal wall and penetrate the organs, mostly liver and lungs. The eggs survive several days outside, depending on the temperature, but numerous eggs die in nature because they cannot resist desiccation and extreme temperatures. Dissemination is accomplished by dogs. In Turkana (Kenya) the incidence of hydatidosis is high because of the close relationship between the population and dogs and the habit of leaving their dead bodies in the grasslands. In rural areas, the custom of slaughtering sheep at home, among the dogs, is an important dissemination factor. The circumstances of transmission vary according to the country. In Europe the natural life cycle of E. granulosus granulosus involves dogs as the definitive host and sheep as the intermediate host. In northern Europe E. granulosus borealis infects the canids and deer. E. granulosus canadensis infects wolves and reindeer, but there are no human cases. In the endemic Mediterranean area, sheep and dromedaries are the intermediate hosts. In South America, the life cycle of E. granulosus develops among several definitive and intermediate hosts. Hence the dynamics of transmission vary according to the countries with different hosts. PMID- 11213155 TI - Hydatid disease of the liver with thoracic involvement. AB - Hydatidosis, caused by Echinococcus granulosus, is an endemic parasitic disease in Mediterranean countries. The most frequent anatomic locations are liver and lung. Intrathoracic rupture of hydatid cysts situated in the hepatic dome is a serious complication resulting in damage to the pleura, pulmonary parenchyma, and bronchi. From January 1984 to December 1997 we operated on 40 patients with intrathoracic rupture of a hepatic hydatid cyst. Chest roentgenograms showed a shadow of varying size at the base of the hemithorax. Hepatic and thoracic ultrasonography was performed in all cases. The diagnosis of intrathoracic rupture of a liver cyst was confirmed preoperatively in 30 of the 40 cases. Posterolateral thoracotomy was performed in all patients. This transthoracic approach allowed adhesiolysis and treatment of the pleural lesions, pulmonary lesions, and hepatic cyst. Treatment of the diaphragmatic gap is easily done. We performed 15 lobectomies, 10 wedge resections, 16 decortications, and in one patient simple drainage of a voluminous pleuropulmonary and hepatic purulent hydatic collection. The postoperative course was uneventful in 26 cases, but 14 patients had complications, from which 3 patients died. The therapeutic approach depends on ultrasonographic findings. We believe ultrasonography to be the best examination for assessing biliary, hepatic, diaphragmatic, and pleuropulmonary lesions. When an intrathoracic collection is present, thoracotomy must be performed and is sufficient if the biliary tract is safe. An abdominal approach is necessary when biliary duct drainage is required, and it may be sufficient in cases of direct rupture into the bronchi. PMID- 11213156 TI - Hydatid cyst of the lung: diagnosis and treatment. AB - Hydatid infestation of the lung can be primary or secondary. In three of four cases the cyst is a single one. Hydatidosis of a different location, particularly the liver, may be associated. The period of initial growth of primary hydatidosis is frequently asymptomatic. Bronchial fistulization is an important event in the evolution of the cyst. Intrapleural rupture constitutes a rare eventuality, but it is often as characteristic as it is severe. Secondary, metastatic hydatidosis, due to breaking of a primary visceral cyst in a vein or heart, is rare. A special form is so-called multiple malignant pulmonary hydatidosis, which causes progressive respiratory deficiency and right ventricular failure. There are a variety of radiographic images. Ultrasonography, computed tomography, and magnetic resonance imaging can recognize certain details of the lesions and discover others that are not visible by conventional radiography. For a specific serologic diagnosis, our experience favors the immunoglobulin G enzyme-linked immunosorbent assay and immunoelectrophoresis. Treatment is essentially surgical. In general, chemotherapy is used as a complement to operative treatment to avoid recurrence. Surgery has two objectives: to remove the parasite and to treat the bronchipericyst pathology and other associated lesions. The prognosis has changed during the last few years, and results are now commonly satisfactory. The most frequent complications are pleural infection and prolonged air leakage. Operative mortality does not exceed 1% to 2%. Despite the low mortality and the limited recurrence rate, it is necessary to remember the invading character of pulmonary hydatid disease, which sometimes makes therapy difficult and questionable. Prophylaxis is essential to eradicate the disease completely. PMID- 11213157 TI - Cardiopericardial hydatid cysts. AB - Cardiac hydatic cyst is a rare parasitic disease. We reported 45 patients with cardiac hydatid cysts; 33 of the 45 had a primitive, unique cardiac cyst. Altogether, 18 patients of our series were asymptomatic, and 27 patients complained of symptoms (dyspnea, chest pain, palpitations). In 11 cases the cyst was revealed by an acute complication; 3 of the 11 had pulmonary metastatic hydatidosis. The diagnosis was based on a series of test results in which hydatid serology and imaging (echocardiography, computed tomography, magnetic resonance imaging) played a predominant role. Cystopericystectomy is the gold standard procedure but is sometimes unsuitable for particular sites. In that case, a conservative approach (partial pericystectomy) is mandatory to preserve organ function. The operative mortality rate is 5.5%. Two pericardial recurrences were reported during follow-up. PMID- 11213158 TI - Hydatid cyst of the kidney: diagnosis and treatment. AB - Renal echinococcosis is relatively uncommon compared to liver and lung localizations. Kidney involvement represents 4% of confirmed cases of hydatid disease. We reviewed the clinical findings of a personal series of renal hydatidosis with emphasis on diagnostic and therapeutic issues. A total of 178 renal cysts were collected over a period of 33 years from 1963 to 1996. Clinical, radiologic and laboratory data are analyzed. Radiologic exploration has had an interesting evolution, with the appearance of ultrasonography and computed tomography. Diagnostic accuracy has been greater since the availability of ultrasonography and immunologic studies. Their contribution to the diagnosis of renal hydatid disease is important. We try, with our experience of ultrasonography in the matter of renal hydatid cysts, to underline the role of this exploration. The treatment of hydatid cyst of the kidney is surgical. Renal sparing surgery, cystectomy plus pericystectomy, is possible in most cases (75%). Nephrectomy (25% of cases) must be reserved for destroyed kidneys resulting from aged cysts opening into the excretory cavities and complicated by renal infection. Whether conservative or radical, the first surgery performed is cystectomy, with germinate membrane removal after controlled evacuation and opening of the cyst, making the subsequent steps of surgery easier. PMID- 11213159 TI - Hydatid cyst of bone: diagnosis and treatment. AB - Osseous hydatidosis is a rare occurrence of hydatid disease. Anatomoclinical changes are, however, peculiar to this localization. From the anatomopathologic standpoint, this localization marks the torpid, insidious progression of the parasite into bone tissue, leading to an immediate diffuse, extensive, invasion process, so complete surgical eradication is rarely possible. From the clinical standpoint, whatever the localization may be, we are surprised by the latency of this affection, the patient being treated at an advanced stage, when radiologic lesions are already extensive, and the complications, especially in the spinal area, are severe. Owing to the poor biologic findings, the diagnosis of osseous hydatidosis is still primarily based on roentgenographic findings. Sometimes, however, the diagnosis is established only after surgery. Treatment of osseous hydatidosis is closer to oncologic therapy than to the usual surgical treatment of visceral hydatid cysts. Because of the poor results with medical treatment, osseous hydatidosis must be treated by a radical operation with wide excision, adapted to each localization. In the main, the prognosis of osseous hydatidosis remains poor, especially with spinal and pelvic localizations, which are the most frequent ones. The prognosis and treatment of osseous hydatidosis belong in the same category as a locally malignant lesion. PMID- 11213160 TI - Recurrence of hydatid disease. AB - Surgical management of hepatic hydatid disease has been associated with an overall local recurrence rate of approximately 10%. Local recurrence is rarely seen following complete resection of an intact cyst and is usually the result of spillage of live parasites or leaving a residual cyst wall containing germinal epithelium, daughter cysts, or protoscolices during surgery. Recurrence is frequently asymptomatic, so the diagnosis depends on dedicated follow-up of treated patients with serology and either ultrasonography or computed tomography. The management of locally recurrent disease should include administration of albendazole followed by the appropriate application of interventional radiotherapy or operation. As with the treatment of primary disease, the preservation of liver function and minimizing the risk to the patient remain the guiding principles of therapy of local recurrence. PMID- 11213161 TI - Evolution of surgery for liver hydatidosis from 1950 to today: analysis of a personal experience. AB - Hydatid disease (echinococcosis) remains a complex worldwide problem in rural areas. Medical treatment does not definitively cure hydatid cysts, and surgical management aims to eliminate the parasite, favoring rapid disappearance of the residual cavity, preventing complications and recurrence, and shortening the hospital stay. In this consecutive series, 298 patients with liver hydatidosis were treated surgically by the authors from 1950 to 1987 in various hospitals in Rome, Italy. Surgery comprised conservative methods (marsupialization and partial cystopericystectomy) and radical methods (total pericystectomy and liver resection). Liver resection was used only if unavoidable. Complications were exudate from the residual cystic cavity, cholerrhagia, and nonspecific incisional fistula. In the entire series, morbidity was 8.7% of which 12.6% was seen with conservative methods and 5.5% with radical methods (p < 0.05); mortality was 3.6%, of which 5.9% was seen with conservative methods and 1.8% with radical methods (p = NS). Over the 37 years, as medical science and complementary therapies progressed, the use of conservative operations diminished and radical treatments increased. Long-term follow-up showed that hydatid disease relapsed more frequently in patients who underwent conservative or subtotally radical treatment than in those who underwent radical surgery: eight patients (11.2%) versus one (0.9%) (p < 0.01). Hence surgical treatment that removes all of the pericyst and preservation of the nonpathologic liver are important. PMID- 11213162 TI - Evaluation of S-100b as a specific marker for neuronal damage due to minor head trauma. AB - Management of patients with minor head trauma (MHT) continues to be debated in the literature. Measurement of S-100b in serum has been introduced into the discussion as an additional screening tool for intracerebral injuries because routine cranial computed tomography (CCT) of a large number of patients causes logistic difficulties, and the neurologic examination is often impaired by a high frequency of coincidental intoxication. The aim of our study was to determine the diagnostic value of measuring S-100b in the serum of MHT patients to identify risk groups. Additional validity should be aquired by a comparison with plasma levels of polymorphonuclear neutrophil (PMN) elastase an established general trauma marker. A series of 52 patients with MHT were included in the prospective study. At admission the patients underwent a routine CCT scan to detect intracerebral lesions, and blood samples were drawn to investigate circulating levels of S-100b and PMN elastase. For comparison, data for a positive control group of 10 severe head trauma patients (initial Glasgow Coma Scale score < 8) and for a negative control group with 20 healthy volunteers were obtained. The interval between MHT and admission to our hospital was 73.4 +/- 47.0 minutes. The initial S-100b serum levels of MHT patients were 0.470 +/- 0.099 ng/ml, those of the positive control group were 7.16 +/- 3.77 ng/ml, and those of the negative control group were 0.05 +/- 0.01 ng/ml. Relevant pathologic CCT scans were detected in 28.8% of MHT patients; one patient of that group was subjected to immediate surgical intervention (1.9%). At a cut-off point of 0.1 ng/ml, the sensitivity of positive S-100b levels reached 100% and the specificity 40.5%. Plasma levels of PMN elastase reached 60.52 +/- 10.75 ng/ml in the MHT group, 66.4 +/- 14.92 ng/ml in the severely head-injured group, and 23.26 +/- 1.53 ng/ml in the negative control group. Serum levels of S-100b seem to be a highly sensitive but not very specific marker for isolated neurotrauma. Measurement of this parameter may be helpful as an additional screening tool to identify high risk groups in the cohort of MHT patients. PMID- 11213163 TI - Indicators of fatigue and of prolonged weaning from mechanical ventilation in surgical patients. AB - Indicators of weaning success have been tested primarily in patients who have been ventilated for short periods of time, and they may not be as accurate in cases where support has been required for longer than a few days. In patients requiring longer periods of support it is difficult to estimate the likelihood of successful liberation. Therefore we evaluated established weaning indices for their accuracy in surgical patients who required > or = 72 hours of mechanical ventilation. Surgical patients who required mechanical ventilation for > or = 72 hours were prospectively followed (over 6 months). We obtained standard indices of ventilatory function daily once patients were ready to wean. These indices included the respiratory rate/tidal volume ratio (RSBI), the maximal inspiratory pressure, and the minute ventilation. The duration of weaning and explicitly defined episodes of fatigue were the outcomes of interest. Statistical analyses evaluated the multiple factors that might influence the duration of weaning. Ninety-five patients (66% trauma; 34% surgery) survived to begin weaning, and 93% were liberated. The median duration of mechanical ventilation prior to weaning was 4 days (range 3-16 days), and the median duration of weaning was 3 days (range 0-56 days). Fatigue occurred in 36 patients and was not reliably predicted by any of the weaning measurements. However, a RSBI of > 105 on the first day of weaning was associated with prolonged weaning. By multivariate analysis, an RSBI of > 105 on the first day of weaning predicted prolonged weaning (hazard ratio 1.9; p = 0.03). After 72 hours of mechanical ventilation, clinical fatigue and successful liberation are not reliably predicted by standard indices of respiratory muscle strength and reserve. However, an RSBI of >105 observed once the patient is ready to wean is associated with prolonged weaning. PMID- 11213164 TI - Contents of minerals in green leafy vegetables cultivated in soil fortified with different chemical fertilizers. AB - Content of selected minerals in spinach (Spinacea oleracea) and ambat chuka (Rumex vesicarius) cultivated in soil fortified with different chemical fertilizers was determined in a pot experiment. Addition of NPK (Nitrogen, Phosphorus and Potassium) fertilizer along with micronutrients, iron and zinc, enhanced the concentration of zinc, iron and magnesium in selected green leafy vegetables markedly (p < 0.05), while the concentration of copper was not altered significantly (p > 0.05). Potassium content in the green leafy vegetables was not affected (p > 0.05) by the addition of chemical fertilizers to soil. Spinach and ambat chuka differed remarkably in their mineral contents. Contents of potassium, zinc and copper were significantly high in spinach, while the contents of magnesium and iron were markedly high in ambat chuka (p < 0.05). PMID- 11213166 TI - Survey of fura production in some northern states of Nigeria. AB - The objective of this research was to conduct a survey related to the production process for fura. Fura is a staple food for the Fulanis and Hausas. The single most important cereal grain for fura production is millet. A significant difference exists among respondents on the variety of millet chosen for fura production. A significantly (p = 0.05) greater proportion indicated that 'gero' is the variety in common use. Spices are indispensable as an ingredient in fura production with ginger being the single most important spice (p = 0.01). The traditional pounding method for processing millet into flour is still very much used. The implication of this is highlighted and a possible solution of optimizing the fura production process is recommended. Strictly speaking, fura is distributed with a minimum of packaging. The choice of suitable packaging provided protection during a generally short shelf-life and for local distribution. With increasing influence of advertising upon customers, small food processing enterprises making fura will have to improve the packaging and preservation of their products if they are to survive the competition. PMID- 11213165 TI - Effect of dietary fiber on the activity of intestinal and fecal beta glucuronidase activity during 1,2-dimethylhydrazine induced colon carcinogenesis. AB - The effects of fiber isolated from black gram (Phaseolus mungo) and coconut (Cocos nucifera) kernel on the metabolic activity of intestinal and fecal beta glucuronidase activity during 1,2-dimethylhydrazine induced colon carcinogenesis were studied. The results indicated that the inclusion of fiber from black gram and coconut kernel generally supported lower specific activities and less fecal output of beta-glucuronidase than did the fiber free diet. This study suggests that the fibers isolated from coconut or black gram may potentially play a role in preventing the formation of colon tumors induced by the carcinogen 1,2 dimethylhydrazine by reducing the activity of the intestinal as well as fecal beta-glucuronidase. PMID- 11213167 TI - Biological evaluation for protein quality of supplementary foods based on popped cereals and legumes suitable for feeding rural mothers and children in India. AB - Eight different formulations of supplementary foods (FS) based on popped cereals (wheat, ragi, bajra and sorghum) and legumes (soy and bengalgram) were prepared. Four of the FS were produced with cereals, soy flour (SF) and bengalgram (BG) dhal and the other four were prepared with combinations of cereals and SF. These blends were evaluated for food efficiency ratio (FER), protein efficiency ratio (PER) and net protein utilization (NPU) using growing albino rats. Skim milk powder (SMP, standard reference protein) was used in the control diet. In general the FER (0.28 to 0.34), PER (2.7 to 2.9) and NPU (62 to 68) results of the FS were not significantly (p > 0.05) different among the FS groups or compared with FER (0.36), PER (3.0) and NPU (73.5) of the control SMP. It is evident from the results that all eight FS were nutritionally and biologically as good as SMP with regard to proximate composition, PER and NPU. PMID- 11213168 TI - Serum and liver lipids in rats fed diets containing corn oil, cottonseed oil, or a mixture of corn and cottonseed oils. AB - Previous research has demonstrated that the total replacement of corn oil (CO) with cottonseed oil (CSO) in the diets of growing male rats results in a lowering of the total cholesterol (TC) concentration in the serum. It is not, however, known if a partial replacement of dietary CO with CSO would be sufficient to lower TC levels, nor is the effect of replacing dietary CO with CSO on other indices of cholesterol status (e.g., the levels of high-density lipoprotein cholesterol [HDL-C], non-HDL-C [i.e., very-low and low-density lipoprotein cholesterol], or the TC/HDL-C ratio). Growing male rats were fed diets having CO, CSO, or a CO/CSO (1:1, w/w) oil mixture (OM) as the source of dietary oil (diet groups CO, CSO, and OM, respectively). There were no differences between CO and OM groups for TC, HDL-C, non-HDL-C, or the TC/HDL-C ratio. However, TC was significantly lower (p < or = 0.05) for the CSO group than the CO group (2.85 vs. 3.23 mmol/l, or 110 vs. 125 mg/dl, respectively) as was HDL-C (1.83 vs. 2.13 mmol/l, or 71 vs. 82 mg/dl, respectively), but there were no differences between these groups for non-HDL-C or the TC/HDL-C ratio. Diet had no effect on serum triglycerides (TGs) or on total liver content of either cholesterol or TGs. Thus, partial (50%) replacement of CO with CSO was without effect on any of these serum indices of cholesterol status, but total replacement resulted in lower TC and HDL C, without affecting non-HDL-C or the TC/HDL-C ratio. Because, relative to CO, CSO has higher levels of saturated fatty acids but lower levels of monounsaturated and polyunsaturated fatty acids, the cholesterol-lowering effect of CSO appears to be unrelated to its fatty acid composition, and may be caused by a component of its nonsaponifiable fraction. PMID- 11213169 TI - Evaluation of selected food attributes of four advanced lines of ungerminated and germinated Nigerian cowpea (Vigna unguiculata (L.) Walp.). AB - The chemical composition and functional properties of ungerminated and germinated seeds of four advanced lines of cowpeas (IT81D-699, IT82E-18, IT84S-2246-4 and TVx 3236) were investigated. Ungerminated seeds contained 20.1 to 25.8% crude protein, 2.0 to 2.2% lipid, 115.1 to 210.0 mg phytic acid/100 g and 8.9 to 9.6 mg iron/100 g. The polyphenol contents of the brown- and cream-colored beans were similar (192.0 to 196.0 mg/100 g) but were significantly (p < 0.05) higher than the amount (99.8 mg/100 g) found in the white beans. Germination increased the crude protein content, total phosphorus content, nitrogen solubility, fat absorption capacity and foam capacity but decreased ether extract, polyphenol and phytic acid contents, water absorption capacity, bulk density and foam stability of all cowpea lines. Incorporation of up to 0.2 M NaCl improved foam volume. Ungerminated seeds had high water (2.3-3.2 g/g) absorption capacities, while germinated seeds had high fat (3.1-3.6 g/g) absorption capacities. TVx 3236 and IT81D-699 might be selected for combining such characteristics as high crude protein, low phytic acid content and good foaming properties into a single cowpea line through breeding. PMID- 11213170 TI - Diplazium sammatii: Athyraceae ('Nyama idim'): age-related nutritional and antinutritional analysis. AB - Tender and mature leaflets and leaves of Diplazium sammatii ('Nyama idim'), were separately investigated for their nutritional and antinutritional properties. Results showed little difference in proximate nutritional contents between tender and mature leaves, except for crude fat, which was present in levels 1.5 times higher in younger than in older leaves. Crude fiber levels were low. Zinc (Zn) and copper (Cu) were higher in younger leaves (6.8 and 3.5 mg/100 g dry matter, respectively, compared to 4.5 and 2.5 mg/100 g dry matter, respectively in older leaves). Older leaves contained higher levels of iron (Fe): 6.7 mg/100 g dry matter, in comparison to 4.3 mg/100 g dry matter, in young leaves. Oxalate levels were slightly higher in younger than older leaves. However, the reverse was true for tannin content. Both antinutritional compounds were present in levels which should be safe. PMID- 11213171 TI - Chemical composition of walnuts (Juglans regia L.) grown in New Zealand. AB - Walnuts (Juglans regia L.) were collected during the 1997 harvest from 12 different cultivars of trees grown in a replicated trial in an experimental orchard at Lincoln University. Two US commercial cultivars (Tehama and Vina), three European commercial cultivars (Esterhazy, G139, G120) and eight New Zealand selections (Rex, Dublin's Glory, Meyric, Stanley, 150, 151, 153) were evaluated. The total oil content ranged from 62.6 to 70.3% while the crude protein ranged from 13.6 to 18.1%. Dietary fiber ranged from 4.2 to 5.2% while the starch content made up no more than 2.8% of the remaining portion of the kernel. The amino acid content of the walnuts was similar between cultivars and the patterns of essential amino acids were characteristic of a high quality protein. PMID- 11213172 TI - Bioavailability trials of beta-carotene from fresh and dehydrated drumstick leaves (Moringa oleifera) in a rat model. AB - Male albino rats (Charles Foster, n = 40) were fed a synthetic diet deficient in vitamin A for 4 weeks. Six rats died during the depletion period. Of the 34 surviving, 5 rats were continued on the vitamin A deficient diet for 4 more weeks and 24 were repleted with vitamin A (4000 IU/kg diet) in the form of vitamin A acetate (group A, n = 8), fresh drumstick leaves (group B, n = 8) or dehydrated drumstick leaves (group C, n = 8) for 4 weeks. The remaining 10 rats were continued on the vitamin A adequate diet for 4 (n = 5) and 8 weeks, respectively (n = 5). A marked reduction in food intake, body weight, accompanied by clinical signs of vitamin A deficiency and a decline in serum vitamin A (29.2 to 19.1 microg/dL) and liver vitamin A (3.7 to 2.0 microg/dL) were seen at the end of 4 weeks of feeding a vitamin A deficient diet. On repletion significant improvements in clinical signs, food intake and body weights were noted in the three groups compared to the baseline (n = 5) and at the end of 4 weeks of depletion. The gain in body weight was highest for the group repleted with dehydrated drumstick leaves. Among the repleted groups, the serum vitamin A was highest for group A (34.7 microg/dL) given synthetic vitamin A, compared to group B (25.8 microg/dL) and group C (28.2 microg/dL) given drumstick leaves. All these were significantly higher than the serum vitamin A values seen at the end of 4 weeks of depletion (19.1 microg/dL). A significant improvement was also observed in the liver retinol levels on repletion for 4 weeks in the three groups, compared to the vitamin A depleted rats. These results imply that beta-carotene from drumstick leaves was effective in overcoming vitamin A deficiency although serum vitamin A levels remained somewhat lower compared to the group repleted with vitamin A acetate. In terms of growth parameters, the fresh and dehydrated drumstick leaves were better than the synthetic vitamin A. It is therefore concluded that in the developing countries like India, sources of vitamin A such as drumstick leaves are valuable in overcoming the problem of vitamin A deficiency. PMID- 11213173 TI - Harmonisation and quality assurance in pre-analytical steps of soil contamination studies--conclusions and recommendations of the CEEM Soil project. AB - The paper summarises the project's results and consequences including expert's statements. Based on sampling strategies and methodological details which have been recognised to be critical for the comparability of the results of soil contamination studies, recommendations are given towards harmonisation of soil sampling guidelines, improvement of quality assurance of pre-analytical steps and inclusion of soil sampling into accreditation systems. Recommended approaches to improve QA and QC in soil sampling are: harmonised guidelines; specified SOPs; written sampling (strategy) plans; defined qualification and experience of sampling personnel; sampling records; regular interlaboratory comparisons (proficency tests) for sampling; and inclusion of sampling and sample preparation into accreditation procedures. Needs for further research in the field of pre analytical phases of soil contamination studies are outlined and further R&D projects are encouraged. PMID- 11213174 TI - Quantifying uncertainty of the reference sampling procedure used at Dornach under different soil conditions. AB - The reference sampling procedure, used in the CEEM soil project on a single test area at Dornach, had been applied under different soil conditions in a sampling proficiency test and in the Swiss national soil-monitoring network related to pollution (NABO). Methods of analysis of variance (ANOVA) were used to quantify sampling and analytical uncertainty. The soil sampling procedure and the chemical analysis were considered as two parts of the same measurement process and the so called 'top-down' approach was used to quantify their combined contribution to the uncertainty. By this approach a systematic error of one sampler or of one laboratory becomes a random error when assessed as part of a multi-sampler or multi-laboratory comparison. PMID- 11213175 TI - Of the necessity of knowledge of the natural pedo-geochemical background content in the evaluation of the contamination of soils by trace elements. AB - In order to evaluate the contamination of the Dornach (Switzerland) site within the framework of the CEEM-Soil project, each participating team was allowed to take a maximum of 15 samples. The French team's sampling was organized in such a way as to answer the following questions: (i) what is the natural concentration of the soils at this site (local pedo-geochemical background content)?; (ii) what are the levels of Cd, Cu, Pb and Zn contamination of the soil?; (iii) what is the depth reached by the surface contamination that is derived from atmospheric fallout?; (iv) how is the contamination spread along the longest axis of the area under study? The relationships between total Fe and the trace metals have allowed local variations in the natural pedo-geochemical background content to be detected and thus permitted the anthropogenic contamination to be estimated. There would appear to be a low level of Pb contamination over all the site investigated (an increase of the order of 5-10 mg kg(-1) on the background level), limited to the surface humus-bearing layers. There is also a significant contamination by Cu over all of the site (an increase of the order of 30-40 mg kg(-1)). This contamination has remained in the surface horizons (0-20 cm). Very high Zn and Cd concentrations have been found in the four surface (0-4 cm) and deep horizons (15-70 cm) taken under the forest and very much lower values in the samples taken from cultivated soils. The most likely explanation is an unequal inheritance between the upper part of the site (wooded with thinner very clayey soils) and the lower cultivated part of the site (with thicker less clayey soils developed in a loamy material). For various reasons, it seems unlikely that a contamination of the wooded part should be so much higher than the cultivated part due to the interception of atmospheric dust by the trees. The local pedo geochemical background Cd and Zn content of the upper wooded part proved to be clearly higher than that which would be encountered in most soils of Switzerland and France. Given this evaluation of the background content, it seems that only the surface horizons have been affected by Zn contamination (an addition of approx. 60-100 mg kg(-1)). In the case of Cd, the increase in concentrations is only 0.5-1 mg kg(-1) for the ploughed horizons, as well as the for the A horizons. PMID- 11213176 TI - A soil sampling strategy for mapping trace element concentrations in a test area. AB - A sampling strategy, based on previous knowledge of a test area, was compared with a Reference Sampling in the frame of the EU-funded CEEM project. The aim was a comparison of sampling strategies for the drafting of concentration maps for a set of trace elements (Cd, Pb, Cu and Zn), with three-dimension information that can be used for risk assessment. The main constraint was that only 15 soil samples were to be analysed. The test area (in Dornach, Switzerland) included different soil types and land uses (forest, arable land and permanent grasslands). The sampling strategy proposed defined strata on the basis of land use, then applying a systematic regular sampling within each stratum. A composite sample was formed from each individual sample. In forests, H and Ah horizons were taken separately. In arable lands, a depth within the ploughed layer (0-15 cm) was analysed. In grasslands, samples were taken at two depths (0-10 and 10-20 cm) to provide information on the vertical variability. The comparison of the results obtained with those derived from the Reference Sampling allowed us to estimate if the information obtained from the proposed sampling strategy was sufficiently representative for an assessment of the level of elements considered. It was concluded that recommendations on sampling strategy depend on the interaction pattern of the element. In this case, for mobile trace elements, such as Cd, the information derived from sampling of two soil layers was not as important as that for the rest of metals studied that accumulated in the upper layer. If the H horizons in forests was not considered this led to unreliable predictions of the concentration levels, since the concentrations in H and Ah horizons differed irrespective of whether they were expressed in mg kg(-1) (the H horizon was enriched in those trace elements, except for Cd) and in mg m(-2) (the low bulk density of the H horizon led to a lower trace element level than in Ah horizon). Finally, in undisturbed systems such as grasslands, sampling 0-10 cm instead of 0 20 cm is recommended to prevent dilution of the concentration of trace elements. PMID- 11213178 TI - Sampling and pre-treatment--some observations from the United Kingdom. AB - This paper arises from the current discussion in the United Kingdom to develop, under the auspices of the British Standards Institution a 'code of practice for investigation of potentially contaminated sites'. Within this code of practice a key element in the analysis is the sampling strategy for the collection of samples and characterisation of the site. The paper briefly summarises the current status of the development of the ideas on the sampling and pre-treatment of potentially contaminated sites, and emphasises the importance which must be attached to the sampling phase of any investigation if the outcomes are to be valid. A brief reference is made to other studies which have addressed the problem of sampling contaminated sites. These studies have considered both the design of the sampling scheme and the number of samples to be taken in relation to the costs of sampling, the nature of the potential hazard, the potential risks involved and the statistical requirements if samples are to be used to predict within given confidence limits. PMID- 11213177 TI - A flexible methodology for the characterisation of soils: a case study of the heavy metal status of a site at Dornach. AB - The sampling scheme devised to study the site at Dornach was successful in identifying most of the features and element distributions in the site using only 15 composite samples. The scheme was based on dividing the area into six individual sampling units each of which represented a different combination of land use and soil type. The three-dimensional information was obtained by taking samples at different depths, either on a fixed depth basis for cultivated soils or according to soil horizons for undisturbed soils. In each sampling unit the composite samples were bulked from 12 individual samples. The sampling point for each individual sample was chosen according to a stratified random plan. Key features of the scheme were the flexibility which required the use of experienced personnel and the fact that the sole task of the sampling exercise was to characterise the site with no preconceptions of possible outcomes. The results showed that the high concentrations of Cd in the soil probably resulted from the high concentrations of Cd in the underlying limestone and not primarily from atmospheric inputs. Higher levels of copper were found in soils close to fruit trees probably as a result of using sprays on the trees. The concentrations of Pb and Zn were relatively uniform throughout the site although there was some evidence of increased Zn concentrations with depth analogous to the Cd distributions. The fact that these findings were in agreement with the known characteristics of the site indicates the successful application of the chosen methodology in this study. PMID- 11213179 TI - An overview of the present state of standardization of soil sampling in Spain. AB - There are no national standard soil sampling guidelines at present in Spain, although a strong need for standardization of sampling activities is evident. Some relevant publications dealing with sampling subjects are cited, and common practices in sampling and sample pre-treatment carried out in Spain for basic soil maps, soil fertility and soil contamination are briefly described. The need to standardize sampling protocols and guidelines in Spain and to harmonize them with those of the EU countries is emphasized. PMID- 11213180 TI - Description of the test area and reference sampling at Dornach. AB - The selected test area for the comparative evaluation of European methods on sampling and sample preparation of soils (CEEM Soil) at Dornach near Basel (Switzerland) is located at approximately 400 m a.S.l. on the north-west rolling footslope of the Jura mountain chain that has a temperate climate. The area is known to be airborne polluted by emissions of a non-ferrous metal recycling plant. The geology is dominated by Jurassic limestone and (decarbonated) loess loam. The land use is deciduous forest (beech, oak) in the upper part and traditional cherry orchards with permanent grassland which have mostly been converted into arable land. The detailed soil survey distinguishes four different soil mapping units in the test area of 0.61 ha. The reference sampling was performed in a 190-m-long and 20-40 m large transect area following four devices: (1) composite samples (0-10 cm and 0-20 cm), each from 25 stratified single samples of 61 squares of 10 x 10 m; (2) hypotheses and soil horizon-based composite samples at nine locations; (3) horizon-related samples from the four described soil profiles representing the mapping units; and (4) three soil cores with 5-cm interval samples taken in the major land use units. Altogether 301 reference soil samples were taken. PMID- 11213181 TI - The Austrian soil sampling procedure tested in a field study (CEEM-project). AB - The Austrian soil sampling procedure requires sampling from representative, uniform areas. For chemical analyses a composite sampling procedure is proposed in which 15-25 single samples should be distributed evenly over the area. Sampling depth for top soils varies between 5 and 30 cm depending on land use. In a field experiment, the suitability and reliability of this sampling method for the determination of trace elements in soil was tested. A high degree of accordance with the results of the extensive and systematic CEEM-Reference Sampling Method was found; therefore the Austrian sampling procedure is recognized as a simple but valid method which can be also proposed as a basis for corresponding ISO- or CEN-Standards. PMID- 11213182 TI - Comparative evaluation of European methods for sampling and sample preparation of soils--the Portuguese contribution. AB - The main purpose of this work was to prepare a Portuguese sampling strategy, according to the existing Portuguese recommendations, for the soil sampling exercise at Dornach in the framework of the CEEM soil project of the SMT Programme of the EU. Within this project, the results obtained from the Dornach study were compared with the results obtained by other European participants and also with the reference sampling. The objective of this comparison was to validate the method used and to evaluate possible factors of uncertainty that may arise from the application of our national guideline as well as possible advantages. Another objective, also important, was to provide information regarding the need for a harmonised procedure within the European Union related to soil sampling and sample preparation of soils. The results obtained were consistent with the results obtained by other participants, however, in the Portuguese recommendations there is a general lack of specific information that may complicate its application to polluted scenarios. In fact, those guidelines are valuable to detect the average contamination of the soil, but they are not useful to identify hot spots or the edge influence in a contaminated land. As a conclusion, the results obtained by the CEEM soil project helped to evaluate the Portuguese sampling plan. This may provide a basis for further standardisation of soil sampling for specific purposes, e.g. contaminated land, and to establish a technical support for criteria used in the accreditation of laboratories for soil sampling. PMID- 11213183 TI - Guidelines for sampling in Flanders (Belgium). AB - In Flanders, sampling guidelines for investigations on contamination of soils are in development. One detailed sampling guideline is currently available with respect to the prospective investigation in the frame of the decree related to soil sanitation. Four strategies for sampling may be followed as a function of available information about pollution sources. Guidelines indicate what has to be sampled (top soil, deeper soil, soil water), how sampling points must be determined, how the number of samples and analyses is determined and what parameters need to be analysed. The example given shows that sampling guidelines will strongly depend on the ultimate goal of a particular sampling. A sampling procedure should be developed with close consideration of practical aspects and limitations, in order to be practical, realistic and cost-effective. PMID- 11213184 TI - Requirements for soil sampling in the context of ecosystem research. AB - Soils are important compartments of ecosystems which are characterized by self regulation within specific limits and different spatial and temporal heterogeneities. Soil sampling has to take into account the sampling strategy, pre-analytical sample processing, extraction and analysis and the interpretation of data as well as quality controls. Some examples from different investigations illustrate special sampling problems under different circumstances. PMID- 11213185 TI - Accreditation and recognition of soil sampling evidence of competence for testing laboratories in Germany. AB - Quality assurance is an essential requirement in many areas of soil testing. Soil sampling plays an important role in soil investigation. One important quality assurance measure is evidence of the competence of institutions offering sampling services (testing laboratories) to carry out appropriate sampling. A special quality assurance procedure has been developed in the course of the investigation and assessment of suspected and contaminated sites on federal property. Testing laboratories are granted official recognition by an independent competent institution, based on well-defined criteria with regard to testing methodology and the qualifications held by the personnel. A prerequisite for such recognition is an effective accreditation procedure. Currently only testing laboratories with recognised status are commissioned for work on contaminated sites on federal property. PMID- 11213186 TI - Analytical aspects of the CEEM soil project. AB - In the past, exercises aiming at an assessment of data uncertainty in environmental analysis were usually restricted to the analysis step, while sampling and pre-analytical sample treatment was largely ignored. Collaborative studies on the quantification of sampling errors require, besides a suitable and well characterized test site, the availability of a reference laboratory for the analysis of all of the samples taken in the context of the study by all participants and also test methods which do not contribute large and variable uncertainties due to long and complex analytical methodologies. Here we summarize the major analytical aspects of a European project on the identification and quantification of sampling influences on the determination of lead, cadmium, copper and zinc in soil. The participant group included the leading soil analysis laboratories in Europe; the test site at Dornach (CH) was well suited for the purpose and showed high metal gradients and differentiated land use. The analytical methods (wavelength-dispersive X-ray fluorescence spectrometry and solid-state Zeeman AAS) used in the study showed stable performance characteristics within the confidence interval of the certified reference materials used for the measurement quality control over the entire project period. Additionally, double-blind tests on split samples showed agreement of data in very narrow limits thus demonstrating the reliability of the reference database. PMID- 11213187 TI - Objectives, concept and design of the CEEM soil project. AB - Within the member countries of the European Union, different strategies and guidelines for the sampling and the preparation of soils are used to investigate soil contamination. As a consequence, there is reasonable doubt that the results gained by applying these different strategies and methods are comparable. In general, the relative contribution of sampling and sample preparation to the total uncertainty in soil contamination studies is a subject of speculation than of knowledge. For this purpose, the first European soil sampling inter-comparison test was organised as a project under the Standards, Measurement and Testing Programme of the European Commission. The aim of this project was to analyse and to compare the existing guidelines, the degree and the state of standardisation in this field in the European countries, and to compare their results when applied on the same test area under comparable conditions by representative sampling teams. The results of the project in general demonstrate that sampling and sample preparation errors reach about the same order of magnitude as errors caused in the chemical analysis. However, there are great differences depending on the elements investigated and their concentration ranges, as well as on pedological and land-use conditions in the test area. Consequently, sampling and sample preparation require the same attentiveness and equivalent measures for quality assurance (QA) and quality control (QC) as the chemical analysis, which has not been the case up to now. Insufficient comparability of the results is illustrated by the fact that different participants arrive at different conclusions for up to 61% of tested soil quality criteria (e.g. threshold levels). The methods and results of the project are presented in detail in the six following papers within this volume. The following 13 papers present some key studies and specific contributions of the participants, as well as synoptical papers of the invited experts in standardisation and accreditation. PMID- 11213188 TI - European soil sampling guidelines for soil pollution studies. AB - The soil sampling guidelines used in European countries (ESSG), as kindly provided by the national institutions which participated in the project, have been recorded, studied, evaluated and presented in this paper. The aim has been to ascertain what soil sampling guidelines exist in Europe; to detect similarities and differences (comparable results), advantages and deficiencies; to identify incompatible strategies and evaluate how methodologies might affect data quality; to investigate sources of deviations or uncertainties; to improve comparability and representativeness of soil sampling; to investigate the need for harmonised sampling guidelines; and to develop suggestions for standard operating procedures (SOP). Soil sampling guidelines throughout Europe differ as to whether they are applied by law, or used throughout the country. In some countries these are ISO/DIS related or based (ISO 10381-1, 1995; ISO 10381-2, 1995), or are produced by a scientific society or a standardisation body. As far as sampling strategy is concerned, not all sampling guidelines clearly describe the sampling scale, the specifications for contamination risk precautions, the sampling plan and protocol structure and the pre-analysis treatment of the soil samples. The purpose for sampling, in descending order of frequency, is soil pollution, soil fertilisation, general soil monitoring, background risk assessment, or else it is not specified. The majority of countries do not sample the top organic matter separately. Sampling depth is either related to the morphogenetic horizon or to ad hoc sampling depth, which is not specified in all cases. They suggest mass- and volume-related soil sampling, while the sampling pattern is not presented in all national guidelines. The criteria for area, site, unit, sub-unit, and point selection are mainly based on pedology and land use, following the history and pre-screening information or geology, or is site related. Some guidelines suggest the division of sampling units into sub-units. The sampling pattern is mainly grid sampling, grid and random sampling, or not mentioned. Sampling density inside the sampling unit either varies greatly or it is not mentioned, while the size of the sampling unit varies widely. Most guidelines require the collection of composite instead of simple samples, while some prefer sampling soil profiles. In the European SSG many technical details and steps are either not defined or vary, while in the pre-analysis treatment quality assurance (QA) and quality control (QC) approaches are used either both in the lab and in the field, or only in the field, or are not mentioned. The common points and the points in which harmonisation could be started or achieved are discussed. PMID- 11213189 TI - Comparative soil sampling in the Dornach site (Switzerland) for soil three dimensional pollution description. AB - Fifteen institutions from 13 European countries and Switzerland participated in a comparative test sampling at the Dornach site, near Basel in Switzerland. They received the site description and were asked to develop their own sampling plans, based on their national guidelines for a three-dimensional description of the Pb, Zn, Cu and Cd pollution, with a maximum of 15 samples. The comparative sampling test took place in late August 1997. The sampling plans and records, provided by the participants, were compared and evaluated in terms of sampling strategy throughout the site, the sampling strategy inside the sampling unit, strategy at the sampling point and last minute alteration of the sampling plans in the field. The object of this was to define the similarities and the differences in the sampling plans and identify the crucial steps inducing error or uncertainty which should be harmonized throughout Europe. The number of the total composite samples varied from 4 to 16, while the number of sampling points varied from 4 to 224 and the sampling density varied from 0.25 to 16 single samples per 100 m2. The number of 10 x 10 m2 quadrats from which samples were taken varied from 3 to 56, out of the total 61. The number of sampling units varied between 3 and 12. The criteria in descending order of frequency were: both land use and pedology, land use, pedology. The majority of the national participants divided the sampling units into two or three sub-units, while seven participants collected replicate composite samples from the same sampling unit. Only one sampled from the existing profiles, eight national representatives ignored the plough depth. The sampling pattern inside the sampling unit was in descending order of frequency: random, point sampling, regular, 'W' and 'X' shaped sampling. The number of single samples in the composite varied from 1 to 20. Most of the national participants sampled to pre-defined (ad-hoc) sampling depths, while others sampled soil horizons and others both. The maximum soil depth sampled also varied from 20 to 117 cm. Most participants mixed in the top organic matter horizon while others sampled it separately. Most sampled separately the top Ah horizon in the forest while the rest mixed it with the underlying soil horizon. The last-minute sampling plan alterations were in: the sampling depth (nine), the movement of sampling points (five), the reduction of sub-samples in the composite sample (four), changes in the number of sampling units (three), ignoring the bottom sample (three), not sampling the L/H layer (three) although this was planned, unplanned sampling of the L/H layer (two) and changing the number of planned samples (two). This study has highlighted the need for soil sampling harmonization throughout Europe for pollution and soil quality determination. PMID- 11213190 TI - Quantitative evaluation of the CEEM soil sampling intercomparison. AB - The aim of the CEEM soil project was to compare and to test the soil sampling and sample preparation guidelines used in the member states of the European Union and Switzerland for investigations of background and large-scale contamination of soils, soil monitoring and environmental risk assessments. The results of the comparative evaluation of the sampling guidelines demonstrated that, in soil contamination studies carried out with different sampling strategies and methods, comparable results can hardly be expected. Therefore, a reference database (RDB) was established by the organisers, which acted as a basis for the quantitative comparison of the participants' results. The detected deviations were related to the methodological details of the individual strategies. The comparative evaluation concept consisted of three steps: The first step was a comparison of the participants' samples (which were both centrally and individually analysed) between each other, as well as with the reference data base (RDB) and some given soil quality standards on the level of concentrations present. The comparison was made using the example of the metals cadmium, copper, lead and zinc. As a second step, the absolute and relative deviations between the reference database and the participants' results (both centrally analysed under repeatability conditions) were calculated. The comparability of the samples with the RDB was categorised on four levels. Methods of exploratory statistical analysis were applied to estimate the differential method bias among the participants. The levels of error caused by sampling and sample preparation were compared with those caused by the analytical procedures. As a third step, the methodological profiles of the participants were compiled to concisely describe the different procedures used. They were related to the results to find out the main factors leading to their incomparability. The outcome of this evaluation process was a list of strategies and methods, which are problematic with respect to comparability, and should be standardised and/or specified in order to arrive at representative and comparable results in soil contamination studies throughout Europe. Pre-normative recommendations for harmonising European soil sampling guidelines and standard operating procedures have been outlined in Wagner G, Desules A, Muntau H, Theocharopoulos S. Comparative Evaluation of European Methods for Sampling and Sample Preparation of Soils for Inorganic Analysis (CEEM Soil). Final Report of the Contract SMT4-CT96-2085, Sci Total Environ 2001;264:181-186. Wagner G, Desaules A, Munatu H. Theocharopolous S, Quevauvaller Ph. Suggestions for harmonising sampling and sample pre-treatment procedures and improving quality assurance in pre-analytical steps of soil contamination studies. Paper 1.7 Sci Total Environ 2001b;264:103-118. PMID- 11213191 TI - Application of waste ashes to agricultural land--effect of incineration temperature on chemical characteristics. AB - Incineration is one of the most important methods of municipal waste disposal. During incineration, various reactions of composition and decomposition may occur; the physical and chemical properties of municipal wastes may change to a great extent. In the present study, 15 samples, including food scraps (FS), animal wastes (AW) and sewage sludges (SS) were collected from various places in Japan, incineration treatments at 500 degrees C, 850 degrees C and 1000 degrees C were conducted in laboratory, and pH, EC, P content, various P forms, anions and soluble metals were determined. The results indicated that average pH increased by 1.09, 1.84, 2.27 and EC decreased by 4.6, 4.6, 5.6 ds m(-1) at 500 degrees C, 850 degrees C, 1000 degrees C, respectively, pH increased in the sequence of AM > SS > FS, and the decrease rate of EC was in the order of FS > SS > AM. Compared with no treatment (NT), water-soluble P decreased greatly at all three temperatures; available P increased at 500 degrees C, but decreased to the original level at 850 degrees C and 1000 degrees C; the amount of Ca-P, Fe-P and Al-P decreased and residual insoluble P increased greatly at 850 degrees C and 1000 degrees C; no significant change of total P was found at all three temperatures. However, water-soluble HPO4(2-) and Cl- decreased greatly, the decrease ratio of Cl- was in the sequence of SS > FS > AM at 500 degrees C, and FS > SS > AM at 850 degrees C and 1000 degrees C; no significant difference was found for HPO4(2-) among all three treatment temperatures; water-soluble SO4(2-) decreased at 1000 degrees C, but there was no significant change at 500 degrees C and 850 degrees C. Moreover, water-soluble Na, Mg, K, Ti, Mn, Fe, Ga, Cd, Zn, Ba, Pb, Sr, W and 0.1 M HNO3 soluble Al, K, Cr, Mn, Fe, Zn, Sr, Ba, Pb, Be, Ga, Rb, Cd, Sn, Sb, Ta, Tl, Bi, Na, Co, Ni, Sc, Cs decreased, but water-soluble Ca, Cr, Co, Ni and 0.1 M HNO3 soluble Cu, Ca, V, Mo, W, Th, U, Hf increased at 500 degrees C, 850 degrees C or 1000 degrees C. PMID- 11213192 TI - Paleonutritional analysis of the pre-Hispanic population from Fuerteventura (Canary Islands). AB - In this study, from histological and chemical perspectives, we analyse the human remains belonging to the pre-Hispanic inhabitants from Fuerteventura (one of the Canary Islands) and compare the results with those obtained on a sample of pre Hispanic inhabitants from Gran Canaria (Canary Islands). We observe that trabecular bone mass was normal in the samples from Fuerteventura except for an elderly woman; this result is in sharp contrast with the decreased bone mass observed in the population from Gran Canaria. The pre-Hispanic population from Fuerteventura showed lower bone strontium, Sr/Ca ratio, and bone barium, but slightly higher bone copper, than that from Gran Canaria. All these data indicate a greater consumption of marine products by the population of Fuerteventura. The high prevalence of osteoporosis observed in the population from Gran Canaria may be interpreted as a consequence of protein-calorie malnutrition, a condition which seemed to be not so prevalent in the population of Fuerteventura. PMID- 11213193 TI - Further evidence for a marine dinoflagellate cyst as an indicator of eutrophication in Yokohama Port, Tokyo Bay, Japan. Comments on a discussion by B. Dale. PMID- 11213194 TI - Marine dinoflagellate cysts as indicators of eutrophication and industrial pollution: a discussion. AB - The results from an investigation of dinoflagellate cysts as indicators of eutrophication in Tokyo Bay, Japan, by Matsuoka [Sci Total Environ 231 (1999) 17] are discussed with reference to other pertinent literature not discussed in the original article. Both the Japanese study and previous work from Norwegian fjords show that pollution (including cultural eutrophication) may produce changes in the phytoplankton reflected by a shift from more autotrophic--to more heterotrophic--dominance of cyst assemblages. However, this is a proportional change that seems likely to result from reduced autotrophic production rather than the increased heterotrophic production suggested by Matsuoka. This is not unequivocal evidence of eutrophication, since Tokyo Bay is impacted also by heavy industrial pollution, the possible effects of which cannot be distinguished, and the quantitative method used for estimating changes in cyst productivity is flawed. PMID- 11213195 TI - A model for determination of motor vehicle emission factors from on-road measurements with a focus on submicrometer particles. AB - The multiplicity of parameters that influence traffic-related emissions and that are often very difficult to measure or predict, makes the assessment of traffic emissions a very complicated process, strongly dependent on local conditions and usually associated with a high degree of error. The aim of this paper was to develop, calibrate and test a simple model for 'on-road' measurements of traffic emission factors as part of a major program focussed on the assessment of traffic contribution to fine and ultrafine emissions to the whole air shed and to local areas in south-east Queensland, Australia. A mathematical model developed was based on the mass balance concept for on-road assessment of traffic-related emission rates. The model requires fewer experimental data points as input and is more applicable to the common on-road testing situation, when no more than two monitors of a specific pollutant can be used. The model was tested and calibrated using experimental data on particle number concentration collected at a road monitoring site using the scanning mobility particle sizer, and was applied to assess the emission factors of submicrometer particles emitted by traffic. The average emission factor obtained using the box model and the experimental data from road measurements was 1.75 x 10(14) particles km(-1) vehicle(-1), with a standard error of 67.6%. While the emission factor obtained was comparable with some results obtained from dynamometer studies and applied to the vehicle mix at the sampling site, they were significantly higher than the factors reported by other studies. PMID- 11213196 TI - Occupational exposure to trihalomethanes in indoor swimming pools. AB - The study evaluated occupational exposure to trihalomethanes (THMs) in indoor swimming pools. Thirty-two subjects, representing the whole workforce employed in the five public indoor swimming pools in the city of Modena (Northern Italy) were enrolled. Both environmental and biological monitoring of THMs exposure were performed. Environmental concentrations of THMs in different areas inside the swimming pools (at the poolside, in the reception area and in the engine-room) were measured as external exposure index, while individual exposure of swimming pool employees was estimated by THMs concentration in alveolar air. The levels of THMs observed in swimming pool water ranged from 17.8 to 70.8 microg/l; the mean levels of THMs in ambient air were 25.6+/-24.5 microg/m3 in the engine room, 26.1+/-24.3 microg/m3 in the reception area and 58.0+/-22.1 microg/m3 at the poolside. Among THMs, only chloroform and bromodichloromethane were always measured in ambient air, while dibromochloromethane was detected in ambient air rarely and bromoform only once. Biological monitoring results showed a THMs mean value of 20.9+/-15.6 microg/m3. Statistically significant differences were observed according to the main job activity: in pool attendants, THMs alveolar air were approximately double those observed in employees working in other areas of the swimming pools (25.1+/-16.5 microg/m3 vs. 14.8+/-12.3 microg/m3, P < 0.01). THMs in alveolar air samples were significantly correlated with THMs concentrations in ambient air (r = 0.57; P < 0.001). Indoor swimming pool employees are exposed to THMs at ambient air levels higher than the general population. The different environmental exposure inside the swimming pool can induce a different internal dose in exposed workers. The correlation found between ambient and alveolar air samples confirms that breath analysis is a good biological index of occupational exposure to these substances at low environmental levels. PMID- 11213197 TI - Concentrations and patterns of organochlorine contaminants in white whales (Delphinapterus leucas) from Svalbard, Norway. AB - Blubber was collected from live-captured, adult male white whales (Delphinapterus leucas) from Svalbard, Norway, and analysed for levels and patterns of organochlorine (OC) contaminants. The OC compounds analysed were HCB, dieldrin, sigmaHCH (alpha-HCH, beta-HCH and gamma-HCH), sigmaChl (heptachlor epoxide, oxychlordane, cis-chlordane, trans-nonachlor, and cis-nonachlor), sigmaDDT (pp' DDT, pp'-DDE and pp'-DDD) and sigmaPCB (27 PCB congeners). The major OC compounds detected in the blubber were sigmaPCB (5103+/-1874 ng/g l.w.) and sigmaDDT (5108+/-1089 ng/g l.w.), which made up 70% of the sigmaOC. These compounds were followed in prevalence by sigmaChl (2872+/-1177 ng/g l.w.), which contributed 20% of the sigmaOC burden. SigmaHCH, HCB and dieldrin were present, but at low concentrations. This OC pattern is typical of top predators in Arctic marine food chains. OC levels in white whales from Svalbard are lower than white whales from the St Lawrence River in Canada and are generally similar to values reported previously for other Arctic white whale stocks. Some geographic patterns in relative prevalence of various OC compounds appear to be quite consistent among various marine mammal species in the Arctic. PCB and DDT concentrations in Svalbard's white whales are below the levels that are thought to have negative effects on reproduction or the immune system. PMID- 11213198 TI - Airborne emission of enriched uranium at Tokai-mura, Japan. AB - A new strategy for characterisation of airborne uranium contamination based on elemental/isotopic analysis of tree bark is described. Bark samples collected at Tokai-mura (Japan) were subjected to high sensitivity ICP mass spectrometric analysis; for control purposes, samples from the remote Yakushima island (Southern Japan) and central Tokyo were also analysed. The uranium contents of tree bark for Tokyo and Yakushima were of similar magnitude to that at Tokai-mura (U, 0.01-1.0 microg/g - all samples), however, there were marked differences in isotope ratio values between the sites. Whereas natural uranium isotope ratio values (235U/238U, 0.0072) were observed for Yakushima and Tokyo, non-natural and natural signatures (235U/238U, 0.00697-0.01448) were realised at Tokai-mura. These findings are consistent with the release of enriched uranium at Tokai-mura. PMID- 11213199 TI - A review of the family Enenteridae Yamaguti, 1958 (Digenea), with descriptions of species from Australian waters, including Koseiria huxleyi n. sp. AB - The family Enenteridae is reviewed, with keys to the genera and species and diagnoses of the family and genera, based on a cladistic analysis utilising 44 characters. Subfamilies are not recognised. Descriptions of the following taxa from Australian marine teleosts are given: Enenterum mannarense from Kyphosus sydneyanus, SW Australia, E. elongatum from Kyphosus sydneyanus, SW Australia (these two species are distinguished by the number of oral lobes and the ovary to anterior testis distance), Koseiria huxleyi n. sp. from Chaetodontoplus meredithi, Great Barrier Reef (this new species is distinguished by the vitellarium reaching into the forebody, the infundibuliform terminal oral sucker, the unlobed ovary and the distinct post-oral ring), Koseiria xishaense from Kyphosus cinerascens and K. vaigiensis, Great Barrier Reef, Cadenatella isuzumi from Kyphosus cinerascens and K. vaigiensis, Great Barrier Reef, and C. pacifica (Yamaguti, 1970) n. comb. [was Jeancadenatia] from Kyphosus cinerascens and K. vaigiensis, Great Barrier Reef. The genus Jeancadenatia is considered a synonym of Cadenatella, and the new combination C. dollfusi (Hafeezullah, 1980) is formed. Members of the family are parasitic mainly in herbivorous fishes with a few genera and species from non-herbivorous fishes. PMID- 11213200 TI - A technique for preserving pigmentation in some capsalid monogeneans for taxonomic purposes. AB - A technique is described to preserve the pigment found in the bodies and the intestine of some brightly coloured and darkly pigmented benedeniine capsalid monogeneans. Previous studies of these pigmented capsalids have proven difficult because the pigmentation usually disappears when the worms are fixed using preservatives containing concentrations of formalin over 5% and/or ethanol, acetic acid, chromic acid, picric acid and mercuric chloride. The technique developed here uses a fixative comprising glycerol, acetone and formalin (GAF). After fixation under light coverslip compression for three minutes, specimens are transferred to absolute acetone for three minutes and cleared in a mixture of nine parts cedar wood oil and one part absolute acetone before mounting in Canada balsam. Processing must be carried out quickly, as these chemicals will cause the pigments to fade if the specimens are exposed to them for too long. Pigmented benedeniines processed using this technique retain the distribution, intensity and colour observed in live worms. The colour and distribution of pigmentation in monogeneans may be of taxonomic importance and this technique aids preparation of whole-mounts suitable for registration as type-material. PMID- 11213201 TI - Allassogonoporus callosciuri n. sp. (Digenea: Allassogonoporidae) from the plantain squirrel Callosciurus notatus (Boddaert) (Rodentia: Sciuridae) in Borneo. AB - A new digenean, Allassogonoporus callosciuri n. sp. from the plantain squirrel Callosciurus notatus from the Malaysian state of Sarawak, Borneo, is described. The new species differs from: A. amphoraeformis by the size of the ventral sucker and the position of the vitellarium and uterus; and from A. marginalis by the smaller oral sucker, the position of the testes and vitellarium; from A. vespertilionis by the position of the vitellarium, testes and ovary; from A. asymmetrica by the position of the testes and uterus. Gilford's (1955) and Dubois' (1963) opinions on the synonymy of Allassogonoporus and Myotitrema is supported. No representatives of the family Allassogonoporidae have been reported previously from sciurids or South-East Asia. PMID- 11213202 TI - Salsuginus neotropicalis n. sp. (Monogenea: Ancyrocephalinae) from the pike killifish Belonesox belizanus (Atheriniformes: Poeciliidae) from southeastern Mexico. AB - Salsuginus neotropicalis n. sp. is described from the gills of Belonesox belizanus (Kner), the pike killifish (Poeciliidae), from the southeastern Mexico. S. neotropicalis is distinguished from all other congeners by the morphology of the haptoral sclerites, especially by the presence of a ventral bar with notably enlarged ends, and by possessing overlapping gonads. The diagnosis of Salsuginus is amended based on the position of gonads in this species. This is the first known Salsuginus species occurring in a freshwater fish from the Neotropical Region. PMID- 11213203 TI - A new species of Isospora Schneider, 1881 (Apicomplexa: Eimeriidae) from the Bali (Rothschild's) mynah Leucopsar rothschildi (Passeriformes: Sturnidae), and comments concerning the genera Atoxoplasma Garnham, 1950 and Isospora. AB - A new species of isosporan (Apicomplexa: Eimeriidae) is reported from the Bali mynah Leucopsar rothschildi (Passeriformes: Sturnidae). Oocysts of Isospora rothschildi n. sp. are spherical to subspherical, 22.3 x 21.6 (20-26 x 19-23) microm, with a shape index (length/width) of 1.03 (1.00-1.15). A micropyle and oocyst residuum are absent, but one to many polar granules are present. Sporocysts are ovoidal, 15.9 x 10.6 (15-18 x 9.5-11) microm, with Stieda and substieda bodies and a shape index of 1.50 (1.39-1.65). Each sporocyst contains an ellipsoidal sporocyst residuum, 8.0 x 5.8 (6-11 x 5-8), and each sporozoite contains two refractile bodies. No correlation was found between the presence of coccidian oocysts in the faeces of some of the birds and Atoxoplasma in blood smears. PMID- 11213204 TI - Pterospora floridiensis, a new species of acephaline gregarine (Apicomplexa) from the maldanid polychaete Axiothella mucosa in St. Andrew Bay, Florida. AB - Pterospora floridiensis, a new species of acephaline gregarine from the body cavity of the bamboo worm Axiothella mucosa (Polychaeta: Maldanidae), is described. The gamont stage is distinctive and possesses a central cytoplasmic mass and two elongate trunks that bifurcate repeatedly and comprise approximately 60% of the total cell length. The gamont averages 198 (50-545) x 71 (25-180) microm (N= 45, 43) from the tip of the trunks to the anterior (the junctional site with the other gamont in syzygy). Gametocysts average 402 (297-545) x 304 (149-495) microm (N = 37). The oocysts measure 22.5 (20.5-23.5) x 8.3 (7.0-10.0) microm (N = 30) and possess an internal capsule (average length = 13.9 microm, N = 30) containing the sporozoites and aliform wings on the epispore. PMID- 11213205 TI - Polystoma macrocnemis n. sp. (Monogenea: Polystomatidae) from the Iranian longlegged wood frog Rana macrocnemis (Ranidae) in Turkey. AB - Polystoma macrocnemis n. sp. (Polystomatidae) is described from the urinary bladder of Rana macrocnemis (Ranidae) in Turkey. Its general morphology is similar to that of other members of the genus, but it is distinguished from closely related species by numerical parameters of the hamuli and also by its host species and geographical range. PMID- 11213206 TI - Monogenea of Chinese marine fishes. XIV. Two new species of Microcotylidae from fishes of the South China Sea. AB - Two new species of microcotylid monogeneans are described. Solostamenides platyorchis n. sp. was obtained from the gills of Mugil cephalus (Mugilidae) and Polylabroides guangdongensis n. sp. from the gills of Sparus macrocephalus, S. berda and Acanthopagrus latus (Sparidae). Solostamenides platyorchis is morphologically similar to S. mugilis (Vogt, 1878) Unnithan, 1971 and S. pseudomugilis (Hargis, 1956) Unnithan, 1971 in the structure of the copulatory organ, but differs from them in the number, arrangement and shape of the testes. Features of P. guangdongensis distinguishing it from other species of the genus include a copulatory organ lacking small spines and an extremely long polar filament on the egg. In view of this species, we suggest omitting the presence of small spines on the copulatory organ as a diagnostic character of the genus Polylabroides Mamaev & Parukhin, 1976. PMID- 11213207 TI - Argulus izintwala n. sp. (Crustacea: Branchiura) from Lake St Lucia, South Africa. AB - During surveys of the fish parasites of Lake St Lucia on the coast of northern KwaZulu-Natal, specimens of an hitherto undescribed argulid were found on the skin of the kelee shad Hilsa kelee (Cuvier). This, only the fourth argulid species to be found in South African coastal waters, is here described as Argulus izintwala n. sp. PMID- 11213208 TI - A pattern correlation model of vestibulo-ocular reflex habituation. AB - Through the process of habituation, the response of the vestibulo-ocular reflex (VOR) is decreased by prolonged, sinusoidal stimulation at lower frequencies (< or =0.1 Hz). Research on goldfish has uncovered frequency-specific and nonlinear behaviors associated with habituation of the goldfish VOR, which include phenomena that cannot be explained using dynamic linear and static nonlinear models. The unexplained phenomena are abrupt decreases at peak response, gain decreases far in excess of linear predictions based on phase, and violation of superposition. Their existence was attributed to a hypothetical switch that closed in the appropriate context. The pattern correlation model provides a new perspective on the process of VOR habituation. Rather than treat the stimulus as a continuous sinusoid, the pattern correlation model breaks it up into a number of discontinuous patterns. The pattern most closely correlated with the current stimulus then decreases the VOR response by the amount of that correlation times a pre-assigned weight. The pattern correlation model explains how the frequency specific and the nonlinear behaviors may be related, and how the apparent switching phenomena may occur. PMID- 11213209 TI - A synthesis procedure for associative memories based on space-varying cellular neural networks. AB - In this paper, we consider the problem of realizing associative memories via space-varying CNNs (cellular neural networks). Based on some known results and a newly derived theorem for the CNN model, we propose a synthesis procedure for obtaining a space-varying CNN that can store given bipolar vectors with certain desirable properties. The major part of our synthesis procedure consists of solving generalized eigenvalue problems and/or linear matrix inequality problems, which can be efficiently solved by recently developed interior point methods. The validity of the proposed approach is illustrated by a design example. PMID- 11213210 TI - The Bifurcating Neuron network 1. AB - The Bifurcating Neuron (BN), a chaotic integrate-and-fire neuron, is a model of a neuron augmented by coherent modulation from its environment. The BN is mathematically equivalent to the sine-circle map, and this equivalence relationship allowed us to apply the mathematics of one-dimensional maps to the design of BN networks. The study of symmetry in the BN revealed that the BN can be configured to exhibit bistability that is controlled by attractor-merging crisis. Also, the symmetry of the bistability can be controlled by the introduction of a sinusoidal fluctuation to the threshold level of the BN. These two observations led us to the design of the BN Network 1 (BNN-1), a chaotic pulse-coupled neural network exhibiting associative memory. In numerical simulations, the BNN-1 showed a better performance than the continuous-time Hopfield network, as far as the spurious-minima problem is concerned and exhibited many biologically plausible characteristics. PMID- 11213211 TI - Optimal control by least squares support vector machines. AB - Support vector machines have been very successful in pattern recognition and function estimation problems. In this paper we introduce the use of least squares support vector machines (LS-SVM's) for the optimal control of nonlinear systems. Linear and neural full static state feedback controllers are considered. The problem is formulated in such a way that it incorporates the N-stage optimal control problem as well as a least squares support vector machine approach for mapping the state space into the action space. The solution is characterized by a set of nonlinear equations. An alternative formulation as a constrained nonlinear optimization problem in less unknowns is given, together with a method for imposing local stability in the LS-SVM control scheme. The results are discussed for support vector machines with radial basis function kernel. Advantages of LS SVM control are that no number of hidden units has to be determined for the controller and that no centers have to be specified for the Gaussian kernels when applying Mercer's condition. The curse of dimensionality is avoided in comparison with defining a regular grid for the centers in classical radial basis function networks. This is at the expense of taking the trajectory of state variables as additional unknowns in the optimization problem, while classical neural network approaches typically lead to parametric optimization problems. In the SVM methodology the number of unknowns equals the number of training data, while in the primal space the number of unknowns can be infinite dimensional. The method is illustrated both on stabilization and tracking problems including examples on swinging up an inverted pendulum with local stabilization at the endpoint and a tracking problem for a ball and beam system. PMID- 11213212 TI - Signal estimation and denoising using VC-theory. AB - Signal denoising is closely related to function estimation from noisy samples. The same problem is also addressed in statistics (non-linear regression) and neural network learning. Vapnik-Chervonenkis (VC) theory has recently emerged as a general theory for estimation of dependencies from finite samples. This theory emphasizes model complexity control according to Structural Risk Minimization (SRM) inductive principle, which considers a nested set of models of increasing complexity (called a structure), and then selects an optimal model complexity providing minimum error for future samples. This paper applies the framework of VC-theory to signal estimation/denoising. There are three factors important for accurate signal estimation from finite samples: (1) the type of (orthogonal) basis functions used (i.e. Fourier basis, wavelets etc.). (2) The choice of a structure, i.e. ordering of the basis functions according to their 'importance' for accurate signal estimation. This corresponds to the choice of a 'structure' under SRM formulation. (3) Selecting an optimal number of terms (basis functions) from the ordered sequence of basis functions (2), aka model selection or complexity control (in statistics). We propose a methodology for specifying appropriate orderings (2) and an analytic expression for model selection (3) for signal processing applications. We also present empirical comparisons between the proposed methodology and current state-of-the-art wavelet thresholding methods for univariate signals. These comparisons suggest that the prudent choice of a structure (2) and the use of VC-based model selection (3) are critical for accurate signal estimation with finite samples. PMID- 11213213 TI - Incremental projection learning for optimal generalization. AB - In many practical situations in neural network learning, it is often expected to further improve the generalization capability after the learning process has been completed. One of the common approaches is to add training data to the neural network. In view of the learning methods of human beings, it seems natural to build posterior learning results upon prior results, which is generally referred to as incremental learning. Many incremental learning methods have been devised so far. However, they provide poor generalization capability compared with batch learning methods. In this paper, a method of incremental projection learning in the presence of noise is presented, which provides exactly the same learning result as that obtained by batch projection learning. The effectiveness of the presented method is demonstrated through computer simulations. PMID- 11213214 TI - Properties of incremental projection learning. AB - We proposed a method of incremental projection learning which provides exactly the same generalization capability as that obtained by batch projection learning in the previous paper. However, properties of the method have not yet been investigated. In this paper, we analyze its properties from the following aspects: First, it is shown that some of the training data which is regarded as redundant in most incremental learning methods have potential effectiveness, i.e. they will contribute to better generalization capability in the future learning process. Based on this fact, an improved criterion for redundancy of additional training data is derived. Second, the relationship between prior and posterior learning results is investigated where effective training data is classified into two categories from the viewpoint of improving generalization capability. Finally, a simpler representation of incremental projection learning under certain conditions is given. The size of memory required for storing prior results in the representation is fixed and independent of the total number of training data. PMID- 11213215 TI - Error correcting memorization learning for noisy training examples. AB - In order to avoid overfitting, we propose error correcting memorization learning. This method is derived from minimization of error between outputs of a trained neural network and correct values for noisy training examples, although the correct values are unknown. We show that noise is adequately suppressed by error correcting memorization learning. The noise suppression mechanism is theoretically clarified. It is found that redundancy plays an essential role for noise suppression and depends on a set of training inputs. We give the condition for the training inputs to provide the redundancy. Moreover, by clarifying the relationships between the proposed method and the weighted least squares estimation with the Mahalanobis norm, we reveal effectiveness of the weighted least squares estimation on noise suppression. PMID- 11213216 TI - A real-coded genetic algorithm for training recurrent neural networks. AB - The use of Recurrent Neural Networks is not as extensive as Feedforward Neural Networks. Training algorithms for Recurrent Neural Networks, based on the error gradient, are very unstable in their search for a minimum and require much computational time when the number of neurons is high. The problems surrounding the application of these methods have driven us to develop new training tools. In this paper, we present a Real-Coded Genetic Algorithm that uses the appropriate operators for this encoding type to train Recurrent Neural Networks. We describe the algorithm and we also experimentally compare our Genetic Algorithm with the Real-Time Recurrent Learning algorithm to perform the fuzzy grammatical inference. PMID- 11213217 TI - A review of molecular recognition technologies for detection of biological threat agents. AB - The present review summarizes the state of the art in molecular recognition of biowarfare agents and other pathogens and emphasizes the advantages of using particular types of reagents for a given target (e.g. detection of bacteria using antibodies versus nucleic acid probes). It is difficult to draw firm conclusions as to type of biorecognition molecule to use for a given analyte. However, the detection method and reagents are generally target-driven and the user must decide on what level (genetic versus phenotypic) the detection should be performed. In general, nucleic acid-based detection is more specific and sensitive than immunological-based detection, while the latter is faster and more robust. This review also points out the challenges faced by military and civilian defense components in the rapid and accurate detection and identification of harmful agents in the field. Although new and improved sensors will continue to be developed, the more crucial need in any biosensor may be the molecular recognition component (e.g. antibody, aptamer, enzyme, nucleic acid, receptor, etc.). Improvements in the affinity, specificity and mass production of the molecular recognition components may ultimately dictate the success or failure of detection technologies in both a technical and commercial sense. Achieving the ultimate goal of giving the individual soldier on the battlefield or civilian responders to an urban biological attack or epidemic, a miniature, sensitive and accurate biosensor may depend as much on molecular biology and molecular engineering as on hardware engineering. Fortunately, as this review illustrates, a great deal of scientific attention has and is currently being given to the area of molecular recognition components. Highly sensitive and specific detection of pathogenic bacteria and viruses has increased with the proliferation of nucleic acid and immuno-based detection technologies. If recent scientific progress is a fair indicator, the future promises remarkable new developments in molecular recognition elements for use in biosensors with a vast array of applications. PMID- 11213218 TI - Simultaneous detection of six biohazardous agents using a planar waveguide array biosensor. AB - Recently, we demonstrated that an array biosensor could be used with cocktails of fluorescent antibodies to perform three assays simultaneously on a single substrate, and that multiple samples could be analyzed in parallel. We extend this technology to demonstrate the simultaneous analysis of six samples for six different hazardous analytes, including both bacteria and protein toxins. The level of antibody cross-reactivity is explored, revealing a possible common epitope in two of the toxins. A panel of environmental interferents was added to the samples; these interferents neither prevented the detection of the analytes nor caused false-positive responses. PMID- 11213219 TI - Single-pad scheme for integrated optical fluorescence sensing. AB - A new scheme for integrated optical fluorescence sensing is presented. The principle is based on a planar waveguide containing multiple sensing units, each consisting of a single-pad grating coupler structure. Single-pad means that all the following functions are incorporated in one single pad: laser light input, excitation of the labeled analyte molecules, efficient collection of the emitted fluorescent light into the waveguide, background suppression, and coupling the guided wave out to the detector. The results demonstrate a high efficiency of the fluorescence light excitation and collection, as well as a good suppression of the volume background. PMID- 11213220 TI - Optical chip immunoassay for hCG in human whole blood. AB - We report on the development of an integrated optic chip sensor for performing rapid and sensitive immunoassays with human whole blood using human chorionic gonadotropin (hCG) as the model system. The optical chip is based on the Hartman interferometer, which uses a single planar lightbeam to address multiple interferometers, each comprising a signal/reference pair of sensing regions. The binding of antigen to specific capture antibodies on the signal sensing region causes a change in the refractive index of the surface layer, which is detectable by its effect on the evanescent field of the guided lightbeam. The reference sensing region is coated with an irrelevant antibody, which optically cancels a large fraction of the non-specific adsorption that occurs on the specific-sensing region when the sensor is tested with clinical specimens. This work extends previous experiments with buffer and human serum to measurements in undiluted whole human blood. Optical chips were stored dry after surface functionalization, and rehydrated with blood. Colloidal gold nanoparticles conjugated to a second anti-hCG monoclonal antibody were used to provide signal amplification, thereby enhancing assay sensitivity, in a one-step procedure with the gold conjugate added to the test sample immediately prior to measurement. Background signals due to non-specific binding (NSB) in blood were found to be higher than those previously reported with human serum. In addition, a high level of background signal was found with the gold conjugate, which had not been observed in experiments with either buffer or serum. Nevertheless, hCG could be detected at 0.5 ng/ml within 10 min of sample application. The sensor response was linear over the concentration range 0.5-5 ng/ml hCG, as compared with the clinically relevant range 0.3-1.5 ng/ml. Detection at higher concentrations was affected by scattering from large amounts of bound gold nanoparticles. However, initial binding rate measurements could be used to maintain assay quantitation. PMID- 11213221 TI - Comparison of surface plasmon resonance and quartz crystal microbalance in the study of whole blood and plasma coagulation. AB - The coagulation of blood plasma and whole blood was studied with a surface plasmon resonance (SPR) based device and a quartz crystal microbalance instrument with energy dissipation detection (QCM-D). The SPR and QCM-D response signals were similar in shape but differing in time scales, reflecting differences in detection mechanisms. The QCM-D response time was longer than SPR, as a physical coupling of the sample to the substrate is required for molecules to be detected by the QCM-method. Change of sample properties within the evanescent field is sufficient for detection with SPR. Both the SPR signals and the QCM-D frequency and dissipation shifts showed dependency on concentrations of coagulation activator and sensitivity to heparin additions. The ratio of dissipation to frequency shifts, commonly considered to reflect viscoelastic properties of the sample, varied with the concentration of activator in blood plasma but not in whole blood. Additions of heparin to the thromboplastin activated whole blood sample, however, made the ratio variation reoccur. Implications of these observations for the understanding of the blood coagulation processes as well as the potential of the two methods in the clinic and in research are discussed. PMID- 11213222 TI - Evaluation of antibody immobilization methods for piezoelectric biosensor application. AB - The immobilization of anti-Salmonella antibodies by two methods were studied and evaluated for their potential use in a piezoelectric biosensor. The optimum temperature-time combinations for the highest immobilization yields were determined for both methods. Protein A binding was found to be 67.4+/-3.8% on the gold surface which then allowed an immobilization of 42.1+/-2.09% antibody. The degree of antibody immobilization via surface aldehyde groups of glutaraldehyde (GA) on a precoated quartz crystal with polyethylenimine (PEI) was 31.6+/-0.3%. A piezoelectric probe was designed and used in dry assays to observe the frequency change due to addition of mass by the immobilization layers. The frequency changes recorded showed a better reproducibility and less added mass for the Protein A method. The frequency decrease due to microg of added antibodies was compared to frequency decrease calculated by the Sauerbrey equation. The experimental data was found to be only approximately 8% of theoretical data. The functionality of the immobilized antibodies with the Protein A method was tested with S. typhimurium in a wet chamber and the frequency decrease was compared to results of a similar system activated with PEI-GA immobilization. The frequency decreases with S. typhimurium concentration of approximately 1.5 x 10(9) CFU/ml were 50+/-2 Hz and 44+/-3 Hz for the Protein A method and PEI-GA method, respectively. It was concluded that although both methods resulted in comparable activities in terms of % immobilized protein and frequency decreases due to Salmonella binding, the Protein A method was favorable due to stability and better reproducibility of the immobilization layers. PMID- 11213223 TI - Preparation of spatially ordered multilayer thin films of antibody and their binding properties. AB - Spatially ordered multilayer thin films containing anti-fluoresceinisothiocyanate (anti-FITC) were prepared on the surface of a quartz slide to study the binding properties of the multilayer films. A quartz slide was treated in solutions of avidin and biotin-labeled anti-FITC alternately and repeatedly to form multilayer thin films through a strong affinity between avidin and biotin. A spectrophotometric study revealed explicitly that the thin films thus prepared consisted of alternate monomolecular layers of avidin and biotin-labeled anti FITC. The antibody retained its binding activity to antigen in the multilayer thin film, though the antigen could not access the antibody embedded deep in the multilayer film. Only the outermost four or five layers of antibody were involved in the binding of antigen. PMID- 11213224 TI - Piezoelectric quartz crystal based label-free analysis for allergy disease. AB - This work presents a piezoelectric (Pz) quartz crystal based label-free quantification of total IgE and allergen-specific IgE in human sera for allergy testing. An evaluation of the different brands of crystals was first initiated with respect to variability in mass sensitivity, frequency measurement reliability and stability, and surface roughness. Thereafter, for total IgE quantification. a direct assay format was adopted. By means of thioctic acid (TA) and coupling reagents, anti-human IgE antibodies were immobilized on AT-cut Pz crystals (10 MHz). The modified crystals could detect serum IgE directly corresponding to a downward frequency shift. The results showed that silver coated crystals as compared with their gold-coated counterparts provided approximately 1.5 times higher mass detection sensitivity for total IgE in the range of 5-300 IU/ml with a linear regression line, y = 1.8957 x + 1.5603, R2 = 0.995. For the detection of allergen-specific IgE, a sandwiched assay format was used. As the allergen-modified sensor surface captured various classes of associated antibodies (IgE, IgG, etc) and interfering serum proteins as well, the initial frequency shift downwards caused by sera sample incubation would not be proportional to specific IgE levels. Thus, following sample incubation, a second incubation step with secondary anti-human IgE was added to recognize IgE from other bound substances. The frequency shift after secondary antibody binding reflected the amount of allergen-specific IgE proportionally. Compared with 10 MHz crystals, the 20 MHz counterparts provided approximately four times higher mass detection sensitivity for allergen specific IgE in the range of 0.15-17.5 IU/ml with a linear regression line, y = 50.525 x + 107.777, R2 = 0.954. Total IgE and allergen specific IgE assay results of real patients' sera using the Pz sensors agreed well with those obtained by commercially available test kits with correlation coefficient 0.96-0.98. The possibility of regenerating the quartz crystals for further re-use was also dealt with. PMID- 11213225 TI - A comparison of protocols for the optimisation of detection of bacteria using a surface acoustic wave (SAW) biosensor. AB - A dual channel surface acoustic wave (SAW) device has been used as a biosensor to detect two different microorganisms, Legionella and Escherichia coli, simultaneously. A series of experiments was conducted to optimise the use of the SAW for bacterial detection using a novel protocol of coating bacteria on the sensor surface prior to addition of the antibody. Results were compared with an experiment in which a conventional protocol was utilised, where antibody was coated on the sensor surface prior to exposure to bacteria. The concentration of bacteria that attached to the surface of the SAW device was related to the antibody that specifically bound to it and therefore to frequency in a dose dependent fashion. Unlike conventional microbiological techniques quantitative results can be obtained for Legionella and E. coli down to 10(6) cells per ml within 3 h. In addition E. coli was detected down to 10(5) cells per ml in a modified protocol using sheep IgG as a blocking agent. PMID- 11213226 TI - Analyte-receptor binding and dissociation kinetics for biosensor applications: a fractal analysis. AB - A fractal analysis of confirmative nature only is presented for analyte-receptor binding and dissociation kinetics for biosensor applications. Data taken from the literature may be modeled, in the case of binding using a single-fractal analysis or a dual-fractal analysis. The dual-fractal analysis represents a change in the binding mechanism as the reaction progresses on the surface. Relationships are presented for the binding and dissociation rate coefficients as a function of their corresponding fractal dimension, Df or the degree of heterogeneity that exists on the surface. When analyte-receptor binding or dissociation is involved, an increase in the heterogeneity on the surface (increase in Df) leads to an increase in the binding and in the dissociation rate coefficient. It is suggested that an increase in the degree of heterogeneity on the surface leads to an increase in the turbulence on the surface owing to the irregularities on the surface. This turbulence promotes mixing, minimizes diffusional limitations, and leads subsequently to an increase in the binding and in the dissociation rate coefficient (Martin S.J., Granstaff, V.E., Frye, G.C., Anal. Chem., 65, (1991) 2910). The binding and the dissociation rate coefficient are rather sensitive to the degree of heterogeneity, Df,bind and Df,diss respectively, that exists on the biosensor surface. For example, the order of dependence on Df,bind is 19.2 for the binding rate coefficient, kbind for the binding of 0.03-1.0 microM SH-2Ld in solution to 2C TCR immobilized on a surface plasmon resonance (SPR) biosensor (Corr, M., Salnetz, A.E., Boyd, L.F., Jelonek, M.T., Khilko, S., Al-Ramadi, B.K., Kim, Y.S., Maher, S.E., Bothwell, A.L.M., Margulies, D.H., Science, 265, (1994) 946). The order of dependence on Df,diss is -6.22 for the dissociation rate coefficient, kdiss for the dissociation of 250-1000 nM Sophora japonica agglutinin (SJA)-lactose complex from the SPR surface. In general, the technique is applicable to other reactions occurring on different types of surfaces, such as cell-surface reactions. PMID- 11213227 TI - Silver electrodeposition catalyzed by colloidal gold on carbon paste electrode: application to biotin-streptavidin interaction monitoring. AB - A new electrochemical method to monitor biotin-streptavidin interaction on carbon paste electrode, based on silver electrodeposition catalyzed by colloidal gold, was investigated. Silver reduction potential changed when colloidal gold was attached to an electrode surface through the biotin-streptavidin interaction. Thus, the direct reduction of silver ions on the electrode surface could be avoided and therefore, they were only reduced to metallic silver on the colloidal gold particle surface, forming a shell around these particles. When an anodic scan was performed, this shell of silver was oxidized and an oxidation process at + 0.08 V was recorded in NH3 1.0 M. Biotinylated albumin was adsorbed on the pretreated electrode surface. This modified electrode was immersed in colloidal gold-streptavidin labeled solutions. The carbon paste electrode was then activated in adequate medium (NaOH 0.1 M and H2SO4 0.1 M) to remove proteins from the electrode surface while colloidal gold particles remained adsorbed on it. Then, a silver electrodeposition at -0.18 V for 2 min and anodic stripping voltammetry were carried out in NH3 1.0 M containing 2.0 x 10(-5) M of silver lactate. An electrode surface preparation was carried out to obtain a good reproducibility of the analytical signal (5.3%), using a new electrode for each experiment. In addition, a sequential competitive assay was carried out to determine streptavidin. A linear relationship between peak current and logarithm of streptavidin concentration from 2.25 x 10(-15) to 2.24 x 10(-12) M and a limit of detection of 2.0 x 10(15) M were obtained. PMID- 11213228 TI - An integrated NAD+-dependent enzyme-functionalized field-effect transistor (ENFET) system: development of a lactate biosensor. AB - An integrated NAD+-dependent enzyme field-effect transistor (ENFET) device for the biosensing of lactate is described. The aminosiloxane-functionalized gate interface is modified with pyrroloquinoline quinone (PQQ) that acts as a catalyst for the oxidation of NADH. Synthetic amino-derivative of NAD+ is covalently linked to the PQQ monolayer. An affinity complex formed between the NAD+/PQQ assembly and the NAD+-cofactor-dependent lactate dehydrogenase (LDH) is crosslinked and yields an integrated biosensor ENFET-device for the analysis of lactate. Biocatalyzed oxidation of lactate generates NADH that is oxidized by PQQ in the presence of Ca2+-ions. The reduced catalyst, PQQH2, is oxidized by O2 in a process that constantly regenerates PQQ at the gate interface. The biocatalyzed formation of NADH and the O2-stimulated regeneration of PQQ yield a steady-state pH gradient between the gate interface and the bulk solution. The changes in the pH of the solution near the gate interface and, consequently, the gate potential are controlled by the substrate (lactate) concentration in the solution. The device reveals the detection limit of 1 x 10(-4) M for lactate and the sensitivity of 24+/-2 mV dec(-1). The response time of the device is as low as 15 s. PMID- 11213229 TI - Inhibitive determination of mercury and other metal ions by potentiometric urea biosensor. AB - The biosensor with urease entrapped in PVC layer at the surface of pH-sensitive iridium oxide electrode was applied for testing of mercury and other metal ions inhibition on enzymatic reaction. The calculation of inhibition effect was based on the measurement of initial rate of decrease of biosensor potential (proportional to the initial rate of enzymatic reaction) after addition of substrate after inhibition step. Some differences of inhibition extent were observed for various mercury forms (Hg(NO3)2, HgCl2, PhHgCl and Hg2(NO3)2) as well as for other heavy metal ions investigated as potential interferents. Because the method was not specific, it was applied for the determination of total inhibition effect caused by heavy metal ions in water samples. In the case of most cations tested the total recovery of enzyme activity was possible using Tris buffer solution with EDTA and thioacetamide after less than 10 min regeneration time. PMID- 11213230 TI - Society for Vascular Medicine and Biology: a vision for the future. PMID- 11213231 TI - Basis and implications of change in arterial pressure with age. PMID- 11213232 TI - Non-invasively determined ambulatory venous pressure. AB - In view of the resemblance of exercise-induced plethysmographic changes with those obtained by direct venous pressure measurement, we decided to use a combination of photoplethysmography (PPG) and hydrostatic pressure calibration to determine the PPG/pressure relationship. A standard foot dorsiflexion exercise involving stepwise position changing was performed which induced hydrostatic pressure changes that were recorded as the heart-probe distance. A logarithmic PPG/pressure relationship was identified and the resulting ambulatory venous pressure (AVP) was obtained from the PPG/pressure curve. Simultaneous direct AVP was recorded in 14 patients scheduled for venous surgery. 'Non-invasive AVP only' was determined in 24 normal control subjects with a mean value of 19.24 mmHg (+/ 8.79 SD). In the patient group, the direct AVP values were 40.00 mmHg (+/-10.83 SD) compared with the PPG values of 33.07 mmHg (+/-12.94 SD). The resulting correlation was r = 0.8850. By utilizing stepwise leg elevation, a reliable PPG/pressure curve can be established which, in turn, permits AVP determination. It is suggested that this non-invasive AVP determination may serve as a screening test to evaluate non-invasively venous hemodynamics. PMID- 11213233 TI - Therapy of unstable angina with the low molecular weight heparins. AB - Unstable angina is in most cases caused by partial or complete coronary artery occlusion due to the disruption of an atherosclerotic plaque and to thrombus formation. An immediate antithrombotic approach is essential to prevent fatal and non-fatal myocardial infarction, and the combination of aspirin and unfractionated heparin has played a pivotal role in the past years. Low molecular weight heparins have improved pharmacokinetic and pharmacodynamic properties over unfractionated heparin that have resulted in greater efficacy and safety in the field of venous thromboembolism. Low molecular weight heparins can be administered by once or twice daily subcutaneous injections at fixed, weight adjusted doses without the need for monitoring. Because of their potential, many recent clinical trials have evaluated their efficacy and safety in the management of patients with unstable angina. Three low molecular weight heparins have so far been tested: nadroparin, dalteparin and enoxaparin. The results of the published trials confirm that the newer compounds are at least as safe and effective as unfractionated heparin, and offer considerable therapeutic advantages. Nevertheless, the different properties of the three compounds and perhaps the different designs of the clinical trials have led to not entirely comparable findings. PMID- 11213234 TI - Multiple skeletal muscle mitochondrial DNA deletions in patients with unilateral peripheral arterial disease. AB - Peripheral arterial disease (PAD) is associated with metabolic derangements and accumulation of the common 4977 bp mitochondrial DNA (mtDNA) deletion mutation. The current study was undertaken to test the hypothesis that PAD is associated with multiple mtDNA deletions. Gastrocnemius biopsies were obtained from nine patients with unilateral PAD. DNA extracted from the biopsies was analyzed for mtDNA deletions using a primer-shift PCR strategy. Multiple primers and strict, prospective criteria were used to identify deletions. PAD was associated with multiple mtDNA deletions (average of 8.2 distinct deletions in muscle from the hemodynamically affected limb). mtDNA injury was present in both the worse- and less-affected limbs of the unilateral PAD patients, and the estimated degree of mtDNA injury was strongly correlated in the two limbs on an intra-subject basis. The 4977 bp deletion was frequently identified, but was not always the deletion of highest frequency in individual samples. The estimated relative frequency of the 4977 bp deletion was correlated with the overall mtDNA injury in the biopsies. In summary, PAD is associated with mtDNA injury as reflected by multiple deletion mutations. As the mutations are not limited to the ischemic limb in unilateral patients, they are unlikely to contribute to the pathophysiology of claudication. PMID- 11213235 TI - Trial of a novel prostacyclin analog, UT-15, in patients with severe intermittent claudication. AB - Prostacyclin is an endothelially derived vasodilator and inhibitor of platelet aggregation. Despite its therapeutic potential for peripheral arterial disease, the short half-life and chemical instability are barriers to routine therapy. Accordingly, prostacyclin analogs are being evaluated in patients with peripheral arterial disease. State-of-the-art non-invasive ultrasonography allows for serial testing of the hemodynamic effects of vasoactive drugs. The safety, efficacy and hemodynamic effects of UT-15, a novel, long-acting prostacyclin analog, were studied in patients with severe intermittent claudication. A total of eight patients with stable severe intermittent claudication, Fontaine classes IIb-III, were admitted to the hospital for intravenous infusion of UT-15. A symptom limited, dose-escalation protocol was instituted, beginning with placebo and then with increasing dosage at 60-min intervals, followed by a 2-h period of maintenance dose at the maximum well-tolerated infusion rate. The hemodynamic response in the lower limbs was assessed with serial ultrasonography, segmental arterial pressures and pulse volumes. Blood flow in the common femoral artery increased 29% (p = 0.003) by the end of the maintenance period and remained above baseline throughout the washout period (p = 0.044). Blood velocity in the lower limb increased in most of the peripheral arteries. These increases achieved statistical significance in the common femoral artery (p = 0.025) and anterior tibial artery (p = 0.019), and approached significance in the popliteal artery (p = 0.062). In two of four patients in whom blood flow was undetectable before the infusion, arterial blood flow at the ankle level became apparent on ultrasonography during maintenance infusion. UT-15 infusion improved the pulse volume recording (p = 0.016) but the ankle/brachial index did not change significantly. Common side effects at peak dose included headache and nausea. There were no serious adverse events attributable to UT-15 treatment. In most patients, the optimal infusion rate was 10-20 ng/kg per min. In conclusion, ultrasonography is a novel approach for assessing the hemodynamic response to vasoactive agents. UT-15 is well tolerated when given for up to 2 h and increases arterial blood flow and velocity in patients with severe intermittent claudication. PMID- 11213236 TI - Hirudin therapy during thrombolysis for venous thrombosis in heparin-induced thrombocytopenia. AB - Heparin-induced thrombocytopenia (HIT) is the most common drug-related thrombocytopenia. Thromboembolic complications occur in approximately 50% of patients with HIT and result in limb amputation and death in up to 20% and 30% respectively. Because patients with a history of HIT may require future intravenous anticoagulation but have a high-risk of thromboembolism if re challenged with heparin, alternative therapies are necessary when further anticoagulation is indicated. The use of direct thrombin inhibitors in HIT patients who also require thrombolytic therapy offers unique challenges to anticoagulant monitoring and safety. We present a case of progressive ileofemoral deep venous thrombosis in a patient with a history of HIT in order to review the combined use of hirudin and thrombolysis in this setting. PMID- 11213238 TI - Low molecular weight heparins for arterial thrombosis. AB - The use of low molecular weight heparin (LMWH) for the prevention and treatment of venous thromboembolism has been validated by numerous clinical trials and meta analyses over the past 25 years. More recently, the possibility of extending treatment with LMWH to the arterial disease where thrombosis is a prominent feature has led to the planning of many clinical trials, several of which have been already published. LMWH has been tested in settings such as acute coronary syndromes, including myocardial infarction, surgery or percutaneous revascularization for coronary and peripheral arteries, and stroke. In most indications, LMWH has proved to be superior to or at least as effective as unfractionated heparin and it is also easier to administer. PMID- 11213237 TI - Adenosine and chronic ischemia of the lower limbs. AB - Adenosine is an endogenous nucleoside with multiple biological properties which plays a central role in the pathophysiology of tissue ischemia. Adenosine signals an imbalance between oxygen demand and supply, and it initiates responses to redress such a discrepancy. Besides its vasodilating properties, adenosine possesses anti-platelet and anti-neutrophil activities and provides cytoprotection. Adenosine is presumably the main mediator of the preconditioning phenomenon. During ischemia of the lower limbs, adenosine plays a physiological role by inducing vasodilatation and by preventing microcirculatory failure. Exercise training prolongs claudication distance possibly by inducing pulse increases of adenosine and consequently skeletal muscle preconditioning. Moreover, the adenosine increase which follows the administration of some drugs, such as buflomedil and propionylcarnitine, opens new perspectives in the management of leg ischemia. In fact, the concept arises of an ischemic (exercise dependent) or pharmacologic preconditioning in the treatment of patients with claudication. PMID- 11213239 TI - Images in vascular medicine. Mycotic aneurysm. PMID- 11213240 TI - Images in vascular medicine. Elephantiasis nostras verrucosa. PMID- 11213242 TI - Efficacy of adjunctive cricopharyngeus myotomy in supraglottic laryngectomy. AB - This study investigates prospectively the effect of concurrent cricopharyngeus myotomy (CPM) on swallowing following horizontal supraglottic laryngectomy (SL) using fiberoptic, radiographic, and manometric evaluations and suggests possible mechanisms regarding the role of CPM following SL. Six patients undergoing horizontal SL between 1995 and 1997 were enrolled in a prospective evaluation with a followup of 0.5-2.25 years. Three patients underwent concurrent CPM and three did not. Fiberoptic, radiographic. and manometric assessments were performed postoperatively. Although mean resting pressures at the upper esophageal sphincter were reduced significantly by myotomy (12 mm Hg) compared with nonmyotomized patients (57 mm Hg), p < 0.01, no rehabilitative advantage was observed in the former group. In fact, of the myotomized patients, two required feeding gastrostomy tubes with resumption of an oral diet in one year and in two months, respectively, while the nonmyotomized patients were all capable of resuming a full oral diet within four weeks. It appears that CPM provides no rehabilitative advantage in patients undergoing SL. PMID- 11213241 TI - Accuracy of bedside clinical methods compared with fiberoptic endoscopic examination of swallowing (FEES) in determining the risk of aspiration in acute stroke patients. AB - This prospective study was undertaken to determine the accuracy of bedside clinical methods compared with fiberoptic endoscopic examination of swallowing (FEES) for detecting aspiration in acute stroke patients. Fifty patients underwent an examination of their ability to swallow 50 ml of water in 10-ml aliquots. Later their oxygen saturation levels before and after swallowing 10 ml of water were measured using a pulse oximeter. Oxygen desaturation of more than 2%, was considered to be clinically significant. All patients then underwent a FEES assessment by a speech therapist and were followed up during their inpatient stay for evidence of aspiration pneumonia. The oxygen desaturation test had a sensitivity of 76.9% and specificity of 83.3% (chi2 = 18.154, p = 0.00002), while the 50-ml water swallow test had a sensitivity of 84.6% and specificity of 75.0% (chi2 = 18.001, p = 0.00002). However, when these two tests were combined into one test called "bedside aspiration," the sensitivity rose to 100% with a specificity of 70.8% (chi2 = 27.9, p = 0.000001). Five (10%) patients developed pneumonia during their inpatient stay. The relative risk (RR) of developing pneumonia, if there was evidence of aspiration on FEES, was 1.24 (1.03 < RR < 1.49). We conclude that the oxygen desaturation test combined with the 50-ml water swallow test is suitable as a screening test to identify all acute stroke patients at risk of aspiration for further evaluation and management. PMID- 11213243 TI - Oropharyngeal dysphagia in esophageal cancer before and after transhiatal esophagectomy. AB - Although dysphagia is the predominant symptom of esophageal cancer, the nature of the swallowing deficit remains unclear, particularly regarding an oropharyngeal motor component. The present study examined the oropharyngeal swallow in patients with esophageal cancer before and following transhiatal esophagectomy. Videofluoroscopic data were obtained from ten patients with esophageal cancer before and following transhiatal esophagectomy as they swallowed 2-, 5-, and 10 cc aliquots of liquid and puree, and 0.5 and 1 tsp of solid. Each swallow was rated on 36 parameters by three independent judges. Swallow-related hyoid bone movement, computed from digitized segments of the videofluoroscopic data, was compared pre- and postsurgically. All patients showed at least mild abnormality of the oropharyngeal swallow preoperatively. Abnormalities involved all stages of swallowing in nine of the ten patients; however, the oral preparatory/oral stage was relatively more impaired than the pharyngeal stage in the majority of patients. Postsurgically, all patients exhibited at least a mild oropharyngeal swallowing impairment. New or increased postoperative deficits involved the pharyngeal stage of swallowing, whereas oral stage abnormalities were generally improved or unchanged following surgery. Swallow-related hyoid kinematics were highly variable both before and following surgery. Anterior hyoid bone excursion was significantly reduced postoperatively in one patient and significantly increased in one patient. Patients with esophageal cancer exhibit oropharyngeal dysphagia, with different profiles of abnormality before and following esophagectomy. PMID- 11213244 TI - Teaching speech pathology students the interpretation of videofluoroscopic swallowing studies. AB - This article examines a teaching package that was designed to cover the progression of skills agreed to by clinicians and educators as being pertinent to interpreting Videofluoroscopy Swallowing Studies (VFSSs). Sessions taught included knowledge of anatomy and physiology of swallowing, examination and identification of structures and landmarks from radiographs, and the use of an assessment scale such as the Bethlehem Assessment Scale (BAS) to interpret VFSSs. The ability to interpret eight VFSSs using the BAS was used as the final assessment. ANOVA for repeated measures and post hoc tests using Tukey's HSD statistic revealed that there was a statistically significant correlation between students' knowledge of anatomy and physiology and their knowledge of radiographic anatomy. There was a statistically significant correlation between their knowledge of radiographic anatomy and their ability to interpret videofluoroscopic examinations, as assessed using the BAS. There was also a statistically significant correlation between their knowledge of anatomy and physiology and their ability to interpret videofluoroscopic examinations using the BAS. PMID- 11213245 TI - Voluntary and reflex influences on the initiation of swallowing reflex in man. AB - The electrophysiological features of voluntarily induced and reflexive/spontaneous swallows were investigated. In normal subjects, swallows were elicited by infusing water either into the mouth (1-3 ml) or directly into the oropharyngeal region through a nasopharyngeal cannula (0.3-1 ml). For water infused orally, subjects were either requested to swallow voluntarily or instructed to resist swallowing and maintain the horizontal head position until swallowing occurred reflexively. Spontaneous saliva swallowing was investigated in patients with severe dysphagia who had a prominent clinical picture of suprabulbar palsy. Comparisons between different swallowing types were made by measuring the time interval between the onset of submental electromyographic activity (SM-EMG) and the onset of the upward movement of the larynx recorded by a movement sensor. This interval was less than 100 ms, even frequently less than 50 ms, in reflexive/spontaneous swallows, while in voluntarily induced swallows it was substantially longer. The rising time of submental muscle's excitation was also shorter in reflexive/spontaneous swallows. It was suggested that the triggering of voluntarily induced swallows commences more than 100 ms before the onset of swallowing reflex and that this mechanism is under the control of corticobulbar-pyramidal pathways. If the swallowing reflex is triggered within such a short period of time following the onset of SM-EMG, the central control by the bulbar swallowing center should be effective until the end of oropharyngeal swallowing. PMID- 11213246 TI - Effects of age, gender, disease, and multisystem involvement on oxygen saturation levels in dysphagic persons. AB - The purpose of this study was to examine the effects of age, gender, disease, and multisystem involvement on SpO2 levels of 104 dysphagic patients and 77 nondysphagic persons. Results indicated that solid aspirators had lower SpO2 levels than liquid aspirators, penetrators, and nondysphagics. In addition, SpO2 levels varied by age, with older persons having lower levels than younger persons among dysphagics but not among nondysphagics. Patients with COPD had lower SpO2 levels than dysphagics with other disorders. Significant interactions were found among age, gender, and disease. Multisystem involvement was found not to be a factor in SpO2 levels. It was concluded that although normal aging processes reduce swallowing and pulmonary functioning, it became a significant factor only when combined with an assault to the system, such as CVA or COPD. PMID- 11213247 TI - Quantitative evaluation of infant's nonnutritive and nutritive sucking. AB - Two important aspects of the clinical feeding evaluation of infants are the assessment of their nonnutritive and nutritive sucking skills. Nonnutritive sucking is monitored routinely by using a gloved finger and nutritive sucking by observing infants' sucking while bottle feeding. This approach, however. provides only a subjective and descriptive evaluation. In this study, we developed a finger pressure device that allows for quantification of specific measures of nonnutritive sucking. We are proposing that its use, in combination with the nipple/bottle system developed for the monitoring of nutritive sucking. will allow therapists to conduct objective and quantitative evaluations of infants' nonnutritive and nutritive sucking. The suction and expression components of sucking are monitored via two catheters placed at the tip of the index finger of a disposable glove and at the tip of a bottle nipple. The observations made from the standard clinical feeding evaluation and from these two instruments were compared. In addition to providing quantitative measures of sucking, the latter techniques allowed the review/reassessment of data, the monitoring of the maturation of oral motor skills over time, and the comparison of these measures between infants. It is proposed that the concurrent use of these devices will allow therapists to conduct more objective and detailed evaluations of infants' feeding skills than can be obtained at present. PMID- 11213248 TI - Foreign body ingestion in children with severe developmental disabilities: a case study. AB - Dysphagia is common in children with severe developmental disabilities. The nature of these difficulties can predispose them to foreign body ingestion. This article presents a case that highlights the need for vigilance in diagnosing dysphagia in children with multiple and complex developmental disabilities where severe cognitive impairment and an inability to communicate may mask the presence of underlying problems. PMID- 11213249 TI - Screening for dysphagia and aspiration in acute stroke: a systematic review. AB - Stroke is a common problem, producing a variety of neurological problems that affect eating. Dysphagia is a particular concern because of its potential for airway obstruction, malnutrition, and aspiration pneumonia. With chest infection reported in up to 32% of stroke patients, this is a major clinical issue. The following research questions are raised: (1) What are the incidence and outcomes of dysphagia and aspiration in acute stroke? (2) What screening interventions are available to detect dysphagia in patients with acute stroke and what effect have they on patient outcomes? A systematic review was carried out using methods and quality criteria of the NHS Centre for Reviews and Dissemination (1996), focusing on studies of adults with acute stroke. Data were extracted, collated, and presented descriptively. Two hundred forty-eight articles were retrieved with 26 meeting inclusion and quality criteria. Clinical dysphagia is common, associated with a range of deleterious outcomes and clearly linked to development of chest infection. Interpretation of aspiration on videofluoroscopy is not as straightforward but probably also confers additional risk. Further work is required on the relationship between aspiration and pneumonia, and pneumonia prevention. This will include exploration of the effects of screening, and the further development and validation of screening methods. While studies indicate current "best practice," in this important area of patient care further work is urgently required. PMID- 11213250 TI - Case management challenges in pediatric dysphagia. PMID- 11213251 TI - Why are there so many sensory brain maps? PMID- 11213252 TI - The plasminogen activator system: biology and regulation. AB - The regulation of plasminogen activation involves genes for two plasminogen activators (tissue type and urokinase type), two specific inhibitors (type 1 and type 2), and a membrane-anchored urokinase-type plasminogen-activator-specific receptor. This system plays an important role in various biological processes involving extracellular proteolysis. Recent studies have revealed that the system, through interplay with integrins and the extracellular matrix protein vitronectin, is also involved in the regulation of cell migration and proliferation in a manner independent of proteolytic activity. The genes are expressed in many different cell types and their expression is under the control of diverse extracellular signals. Gene expression reflects the levels of the corresponding mRNA, which should be the net result of synthesis and degradation. Thus, modulation of mRNA stability is an important factor in overall regulation. This review summarizes current understanding of the biology and regulation of genes involved in plasminogen activation at different levels. PMID- 11213253 TI - A structural view of microtubule dynamics. AB - The essential microtubule property of dynamic instability is based on the binding, hydrolysis and exchange of GTP in each tubulin dimer. The recent high resolution structures of tubulin and the microtubule have given us the first view at atomic level of properties such as nucleotide exchangeability, the linkage between polymerization and nucleotide hydrolysis. and the origin of microtubule destabilization, as well as the mode of action of antimitotic agents such as taxol. PMID- 11213254 TI - Dual Valpha T cells. AB - The assumption that T cells can only express a single receptor for antigen has in recent years been shown to be incorrect. However, the finding that a substantial number of T cells express two distinct antigen receptors at the cell surface raises a number of questions. In particular, it has been suggested that cells expressing low levels of a self-reactive T cell receptor may escape self tolerance mechanisms and in certain situations trigger the onset of autoimmune disease. Such a hypothesis in turn raises questions central to the understanding of the nature of T cell recognition and the process of thymocyte maturation. PMID- 11213255 TI - Regulation of plant ferritin synthesis: how and why. AB - Plant ferritins are key iron-storage proteins that share important structural and functional similarities with animal ferritins. However, specific features characterize plant ferritins, among which are plastid cellular localization and transcriptional regulation by iron. Ferritin synthesis is developmentally and environmentally controlled, in part through the differential expression of the various members of a small gene family. Furthermore, a strict requirement for plant ferritin synthesis regulation is attested to by alterations of the photosynthetic apparatus and of iron homeostasis in transgenic tobaccos overexpressing these proteins. Plant ferritin gene regulation appears to consist of a complex interplay of transcriptional and posttranscriptional mechanisms, involving cellular relays such as plant hormones, oxidative steps and Ser/Thr phosphatase. PMID- 11213256 TI - Arachidonic acid release by ionomycin and phorbol ester is similar in C127 epithelial cells expressing wild-type or mutated (delta F508) cystic fibrosis transmembrane conductance regulator. AB - The Ca2+ ionophore ionomycin induced cytosolic [Ca2+ ]i elevation as well as strong activation of Cl- efflux in mouse mammary epithelial cell lines expressing wild-type or mutated (deletion of phenylalaline 508) cystic fibrosis transmembrane conductance regulator (CFTR) or vector. Ionomycin-induced Cl- efflux was abolished by the intracellular Ca2+ chelator 1,2-bis(2 aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, whereas both activators and inhibitors of phospholipase A2 had no effect, indicating the involvement of Ca2+ dependent Cl- channels. Stimulation of arachidonic acid release by ionomycin and phorbol ester was not significantly different between wild-type or mutated cell lines, whereas vector-transfected cells exhibited a significant higher release, which was shown to be due to larger amount of immunoreactive cytosolic phospholipase A2. These results indicate that phospholipase A2 activity of C127 cells was not influenced by the presence of wild-type or mutated CFTR. PMID- 11213257 TI - Spleen antibacterial peptides: high levels of PR-39 and presence of two forms of NK-lysin. AB - Antibacterial peptides were isolated from porcine spleen by acetic acid extraction, ion exchange chromatography and reverse-phase high-performance liquid chromatography. C-terminal ladder sequence analysis of a bioactive peptide with matrix-assisted laser desorption/ionization mass spectrometry after digestion with carboxypeptidases P and Y showed that it is identical to the antibacterial proline/arginine-rich intestinal peptide PR-39. It is present at high levels in granulocytes of the spleen, and peptides with C-terminal proline amide and internal adjacent Pro residues can be analyzed with this method. In addition, two forms of NK-lysin (NKL) were found. One, NKLi, is identical to that isolated from pig intestine, and the other, NKLbw, to a mature peptide deduced from a clone from a porcine bone marrow cDNA library. PMID- 11213258 TI - Small nucleolar RNAs. AB - Many small RNA species associate with the nucleolar structure. Some of these small nucleolar RNAs (snoRNAs) are required for cleavage processing of ribosomal RNA precursors. There are many pseudouridine residues and methylated riboses in mature ribosomal RNA. For most, if not all, of these modifications, each site is selected by base pairing with a specific snoRNA species. Some snoRNAs are needed for the 2'-O-ribose methylation of at least one spliceosomal small nuclear RNA. Many snoRNAs, particularly in yeast, are generated from independent transcription units. Most vertebrate snoRNAs are produced by processing of introns from protein coding transcripts. Some snoRNAs are made by processing of introns from non protein-coding transcripts. PMID- 11213259 TI - Epithelial antimicrobial peptides: innate local host response elements. AB - Multicellular organisms have to survive in an environment laden with numerous microorganisms, which represent a potential hazard to life. Different strategies have been developed to ward off infections by preventing microorganisms from entering surfaces and by preventing the attack of microorganisms that have already entered the epithelia. Therefore, it is not surprising that epithelia are equipped with various antimicrobial substances that act rapidly to kill a broad range of microorganisms. This review summarizes our present knowledge about epithelial peptide antibiotics produced in plants, invertebrates, and vertebrates including humans. There is now strong evidence that in addition to constitutively secreted peptide antibiotics, others are induced upon contact with microorganisms or by proinflammatory cytokines. beta-Defensins represent one family of vertebrate antimicrobial peptides, members of which are inducible and have recently been identified in humans. The defensin-characteristic local expression pattern may indicate that specialized surfaces express a characteristic surface antimicrobial peptide pattern that might define the characteristic microflora as well as the density of microorganisms present on the surface. PMID- 11213260 TI - Botulinum toxin as a carrier for oral vaccines. AB - Botulinum toxin is an unusually potent substance that acts on the nervous system to produce the clinical outcome of flaccid paralysis. To produce this effect, the toxin ordinarily proceeds through two separate but essential sequences of events. During the first, the toxin is ingested, it traverses a portion of the gastrointestinal system and then it is transcytosed from the lumen of the gut to the general circulation. During the second, circulating toxin binds to peripheral cholinergic nerve endings, it is endocytosed and then it acts as a metalloendoprotease to cleave polypeptides that are essential for exocytosis. Although botulinum toxin is antigenic, it ordinarily does not evoke an immune response during or after cases of oral poisoning. This is due to the fact that the dose of toxin that produces flaccid paralysis-and potentially death-is less than the dose needed to evoke an antibody response. In the recent past, the techniques of molecular biology have been used to generate an expression product of botulinum toxin that retains the ability to escape the gut and reach the general circulation, retains the ability to evoke an immune response, but has lost the ability to produce neurotoxicity. This modified toxin may have two clinical applications. The expression product itself may have utility as an oral vaccine against botulism. Beyond this, the modified toxin, or a truncation mutant of the toxin, may have utility as a carrier in the construction of other oral vaccines. Both potential applications could lead to the expression of oral vaccines in common foods. PMID- 11213261 TI - Antigen-specific T cells in autoimmune diseases with a focus on multiple sclerosis and experimental allergic encephalomyelitis. AB - Although the pathogenesis of autoimmune diseases remains poorly understood, the current view is that autoaggresive antigen-specific T cells play a central role in the cascade of events leading to most autoimmune diseases. A major event in the development of autoimmune diseases is the activation of antigen-specific T cells-how, when and where does this activation take place? This review addresses questions concerning the occurrence of unique autoantigens triggering autoimmune diseases, the factors influencing the balance between self-tolerance and autoaggresive immunity, and the mechanisms by which dendritic cells mediate immunity and tolerance to antigen-specific T cells. Knowledge of how antigen specific T cells are activated is now being used to develop therapeutic approaches to control autoimmune diseases. We discuss tolerance to antigen specific T cells and tolerance induction as treatment of T-cell-mediated autoimmune diseases. Therapeutic modalities have been established which selectively target the pathogenic T cells. leaving the remainder of the immune system intact. PMID- 11213262 TI - Netrins and netrin receptors. AB - The formation of precise connections between neurons and their targets during development is dependent on extracellular guidance cues that allow growing axons to navigate to their targets. One family of such guidance molecules. conserved across all species examined, is that of the netrin/UNC-6 proteins. Netrins act to both attract and repel the growing axons of a broad range of neuronal cell types during development and are also involved in controling neuronal cell migration. These actions are mediated by specific receptor complexes containing either the colorectal cancer (DCC) or neogenin protein, in the case of the attractive receptor, or UNC-5-related proteins, in the case of the repellent receptor. Recent work has identified a key role for intracellular cyclic nucleotide levels in regulating the nature of the response of the growing axon to netrins as either attractive or repulsive. Netrin-DCC signaling has also been shown to regulate cell death in epithelial cells in vitro, raising the interesting possibility that netrins may also regulate cell death in the developing nervous system. PMID- 11213263 TI - Memory T lymphocytes. AB - Immunological memory protects organisms from recurrent challenge by pathogens. The persistence of a heightened reactive state initiated by antigenic challenge is mediated by long-lived memory lymphocytes. The survival of memory T cells is thought to require stimulation through the T cell receptor (TCR), sometimes by persistent antigen. However, memory T cells can survive in the absence of antigen, in which case TCR stimulation provided by cell surface self-peptide/ major histocompatibility complex (MHC) molecules and cytokines are required to sustain memory T cells. Recent work using mouse models has provided insights into the origin of memory T cells. Understanding the mechanisms that underlie the differentiation and persistence of memory T cells may improve the effectiveness of vaccines through the induction of T cell memory. PMID- 11213264 TI - alpha-Endosulfine, a new entity in the control of insulin secretion. AB - ATP-dependent potassium (K ATP) channels occupy a key position in the control of insulin release from the pancreatic beta cell since they couple cell polarity to metabolism. These channels close when more ATP is produced via glucose metabolism. They are also controlled by sulfonylureas, a class of drugs used in type 2 diabetic patients for triggering insulin secretion from beta cells that have lost part of their sensitivity to glucose. We have demonstrated the existence of endogenous counterparts to sulfonylureas which we have called 'endosulfines.' In this review, we describe the discovery, isolation, cloning, and biological features of the high-molecular-mass form, alpha-endosulfine, and discuss its possible role in the physiology of the beta cell as well as in pathology. PMID- 11213265 TI - Evolution of the genetic code, protein synthesis and nucleic acid replication. AB - A better definition of the structural and thermodynamic determinants of the interaction of nucleic acids with proteins is shedding light on the origin of the genetic code, protein synthesis, and nucleic acid replication. This is also allowing to show a consistent biochemical framework for the appearance of these fundamental synthetic mechanisms. This article reviews recent significant developments in the field, and discusses an integrated model for a biochemically plausible evolution of these fundamental mechanisms of synthesis. This model is based on sequence-specific interactions between abiotically synthesized polynucleotides and polypeptides, and can account for a coordinate evolution of the genetic code, protein synthesis, and nucleic acid replication in living cells. PMID- 11213266 TI - Evolutionary diversification of the mammalian defensins. AB - Defensins are cysteine-rich cationic peptides that function in antimicrobial defense in both invertebrates and vertebrates. Three main groups of animal defensins are known: insect defensins; mammalian alpha-defensins and vertebrate beta-defensins. It has been difficult to determine whether these molecules are homologous or have independently evolved similar features, but overall the evidence favors a distant relationship. The best evidence of this relationship is structural, particularly from their overall three-dimensional structure and from the spacing of half-cystine residues involved in intra-chain disulfide bonds. Some evidence favors a closer relationship between vertebrate beta-defensins and insect defensins than between the two groups of vertebrate defensins. Examination of nucleotide substitutions between recently duplicated mammalian defensin genes shows that the rate of nonsynonymous (amino-acid-altering) substitution exceeds that of synonymous substitution in the region of the gene encoding the mature defensin. This highly unusual pattern of nucleotide substitution is evidence that natural selection has acted to diversify defensins at the amino acid level. The resulting rapid evolution explains why it is difficult to reconstruct the evolutionary history of these molecules. PMID- 11213267 TI - Interpretation, design, and analysis of gene array expression experiments. AB - Experiments using arrays of cDNA targets to compare patterns of gene expression are beginning to play a prominent role in biogerontology, but drawing reliable conclusions from the resulting data sets requires careful application of statistical methods that discriminate chance events from those likely to reflect real differences among the samples under study. This essay discusses flaws in the logic of studies that base their conclusions on ratio calculations alone, reviews the multiple comparison traps inherent in high throughput systems that test a very large number of mRNAs simultaneously, and advocates a two-stage design in which significance testing applied to exploratory data is used to guide a second round of hypothesis-testing experiments conducted in a separate set of experimental samples. PMID- 11213268 TI - Age, fatigue, and excitation-contraction coupling in masseter muscles of rats. AB - The purpose of this study was to determine if masseter muscle endurance changes with increasing age and, if so, to examine mechanisms of fatigue. Characteristics of fatigue were measured under isometric conditions using high-frequency stimulation of anterior deep masseter (ADM) muscles of male Fischer 344 rats, 5 to 24 months old, and fed a hard (HD) or a soft (SD) diet. Potentiating effects of caffeine on ADM muscle performance in vitro were also examined. Fatigability increased by 48% with age in muscles of HD rats. Muscles of SD rats were highly fatigable at all ages. Increased HD fatigability was associated with significantly decreased concentrations of Na+/K+-adenosine triphosphatase (22%) and decreased responsiveness to caffeine postfatigue (29%). The pH levels decreased similarly in fatigued muscles of all groups. We conclude that the age related increase in fatigability is associated with alterations in excitation contraction coupling mechanisms. However, differences between SD and HD on ADM muscles represent possible fiber-type transitions. PMID- 11213269 TI - Age-related differences in hippocampal extracellular fluid glucose concentration during behavioral testing and following systemic glucose administration. AB - Recent evidence indicates that the level of glucose in the brain's extracellular fluid (ECF) is not constant, as traditionally thought, but fluctuates. We determined the effect of aging on hippocampal ECF glucose before, during, and after spatial memory testing. Fischer-344 rats (24 months old) showed a greater decrease in ECF glucose than 3-month-old rats (48% vs 12%); the decrease seen in 24-month-old rats persisted for much longer following testing. These changes were associated with an age-related deficit in spontaneous alternation performance. Following systemic glucose administration, the decrease in ECF glucose was reversed in both aged and young rats, and performance in aged versus young rats following glucose administration did not differ. These findings suggest that increased susceptibility to depletion of ECF glucose in aged rats may contribute to age-related deficits in learning and memory and that administration of glucose may enhance memory by providing additional glucose to the brain at times of increased cognitive demand. PMID- 11213270 TI - Array-based expression analysis of mouse liver genes: effect of age and of the longevity mutant Prop1df. AB - Ames dwarf mice, homozygous for the df allele at the Prop1 locus, live 40% to 70% longer than nonmutant siblings and represent the first single-gene mutant that extends life span in a mammal. To gain insight into the basis for the longevity of the Ames dwarf mouse, we measured liver mRNA levels for 265 genes in a group of 11 df/df mice, (three to four mice per age group), at ages 5, 13, and 22 months, and in 13 age- and sex-matched control mice. The analysis showed seven genes where the effects of age reach p < .01 in normal mice and six others with possible age effects in dwarf mice, but none of these met Bonferroni-adjusted significance thresholds. Thirteen genes showed possible effects of the df/df genotype at p < .01. One of these, insulin-like growth factor 1 (IGF-1), was statistically significant even after adjustment for multiple comparisons; and genes for two IGF-binding proteins, a cyclin, a heat shock protein, p38 mitogen activated protein kinase, and an inducible cytochrome P450 were among those implicated by the survey. In young control mice, half of the expressed genes showed SDs that were more than 58% of the mean, and a simulation study showed that genes with this degree of interanimal variation would often produce false positive findings when conclusions were based on ratio calculations alone (i.e., without formal significance testing). Many genes in our data set showed apparent young-to-old or normal-to-dwarf ratios above 2, but the large majority of these proved to be genes where high interanimal variation could create high ratios by chance alone, and only a few of the genes with large ratios achieved p < .05. The proportion of genes showing relatively large changes between 5 and 13 months, or from 13 to 22 months of age, was not diminished by the df/df genotype, providing no support for the idea that the dwarf mutation leads to global delay or deceleration of the pace of age-dependent changes in gene expression. These survey data provide the foundation for replication studies that should provide convincing proof for age- and genotype-specific effects on gene expression and thus reveal key similarities among the growing number of mouse models of decelerated aging. PMID- 11213271 TI - Interleukin-6 production does not increase with age. AB - Investigators have reported an increase, decrease, or no effect of age on interleukin-6 (IL-6) production. Differences in experimental conditions and the health status of subjects may explain these contradicting results. Because the subjects used in most of the previous studies were not carefully screened for health, we investigated the effect of age on IL-6 production in healthy young and elderly subjects. Twenty young (aged 20-30 years) and 26 elderly (>65 years) men completed the study. Each subject was screened for good health, undergoing physical examinations and laboratory tests. Circulating IL-6 levels were not significantly different between young and elderly subjects. A subgroup of subjects representing both young and elderly volunteers had high (>1000 pg/ml) circulating levels of IL-6. However, circulating IL-6 levels were low (<100 pg/ml) in the majority of subjects in both age groups. Peripheral blood mononuclear cells (PBMC) were cultured for IL-6 production in the presence or absence of phytohemagglutinin (PHA) or concanavalin (Con)A for 48 hours. Unstimulated secretion of IL-6 by PBMC cultured in autologous plasma (AP) or fetal bovine serum (FBS) was detectable in the majority of cultures. Age did not influence this spontaneous secretion of IL-6. PBMC stimulation with PHA or ConA significantly increased IL-6 production, but age did not affect the ability of PBMC to secrete IL-6 after stimulation when cultured in FBS. IL-6 production by PBMC cultured in AP and stimulated with PHA was not affected by age. However, when stimulated with ConA, PBMC from the elderly subjects produced less IL-6 than PBMC from the young subjects. Because IL-6 has been suggested to contribute to the age-related increase in prostaglandin (PG)E2 and nitric oxide (NO) production, we investigated the effect of age on the production of IL-6 by murine peritoneal macrophages (Mphi) as well as the effect of IL-6 on the production of other Mphi inflammatory products. Similar to the findings in humans, mouse age did not influence the level of IL-6 produced by Mphi. These data suggest that in healthy subjects, increased production of IL-6 is not a normal consequence of aging. Previously reported higher IL-6 levels in elderly subjects might reflect an underlying, undiagnosed disease state. PGE2 and NO production were not affected by the addition of IL-6 to Mphi from young mice or anti-IL-6 antibody to Mphi from old mice. Thus, IL-6 does not appear to influence the Mphi production of selected inflammatory molecules. PMID- 11213273 TI - The effects of a collaborative model of primary care on the mortality and hospital use of community-dwelling older adults. AB - BACKGROUND: This study evaluates the ability of a model of collaborative primary care practice to reduce mortality and hospital use in community-dwelling elderly persons. METHODS: Four rural and four urban clinic sites in east central Illinois were randomized to form treatment and comparison clinics from which patients were enrolled and followed prospectively for 2 years. Patients from the practices of participating physicians were eligible if they were aged 65 and older, were living in the community, and had at least one risk factor as determined prior to the study. Medicare hospital data were obtained from the Health Care Financing Administration. Demographic and health status measures were obtained by telephone interview every 12 months throughout the study. RESULTS: The treatment group experienced a 49% reduction in all-cause mortality during the second year of the study (odds ratio, 0.51, 95% confidence interval, 0.29-0.91, p = .02). There were no significant differences between treatment and comparison patients in percentage of persons hospitalized, hospital length of stay, or Medicare payments. Although measures of health status indicated that the treatment group was significantly sicker at baseline at the end of 1 year, these differences disappeared by the end of 2 years. CONCLUSIONS: The collaborative primary care model evaluated in this study significantly reduced mortality in the second year, without increasing hospital use. These findings suggest that a collaborative primary care team that enhances primary care practice can result in better patient outcomes. PMID- 11213272 TI - Female sensitivity to diet and irradiation treatments underlies sex-mortality differentials in the Mediterranean fruit fly. AB - Large-scale experiments on medflies that were subjected to sterilizing doses of ionizing radiation (plus intact controls) and maintained on either sugar-only or full, protein-enriched diets revealed that, whereas the mortality trajectories of both intact and irradiated male cohorts maintained on both diets are similar, the mortality patterns of females are highly variable. Mean mortality rates at 35 days in male cohorts ranged from 0.2 to 0.3 but in female cohorts ranged from 0.09 to 0.35, depending on treatment. The study reports three main influences: (a) qualitative differences exist in the sex-mortality response of medflies subjected to dietary manipulations and irradiation; (b) the female mortality response is linked to increased vulnerability due to the nutritional demands of reproduction; and (c) female sensitivity to environmental changes underlies the dynamics of the sex-mortality differential. PMID- 11213274 TI - Sildenafil citrate (VIAGRA) improves erectile function in elderly patients with erectile dysfunction: a subgroup analysis. AB - BACKGROUND: The prevalence of erectile dysfunction (ED) increases with advancing age, with a particularly high prevalence of ED in elderly patients with diabetes. In the United States it is estimated that approximately 45% of men aged 65 to 69 years have moderate or complete ED. The efficacy and safety of oral sildenafil (VIAGRA) for treating ED in elderly men (aged > or = 65 years or older) were assessed. METHODS: We analyzed data obtained from five double-blind, placebo controlled studies of the efficacy and tolerability of oral sildenafil taken as required (but not more than once daily) over a 12-week to 6-month period. Two subgroups were evaluated: (i) elderly patients with ED of broad-spectrum etiology (n = 411), and (ii) elderly patients with ED and diabetes (n = 71). Efficacy was assessed using a global efficacy question, questions 3 and 4 of the International Index of Erectile Function (IIEF). and the five sexual function domains of the IIEF. RESULTS: All efficacy assessments indicated that sildenafil significantly improved erectile function both in elderly patients with ED of broad-spectrum etiology and in elderly patients with ED and diabetes. The most common adverse events were mild-to-moderate headache, flushing, and dyspepsia. The rates of discontinuation due to adverse events were low and were comparable to the rates with placebo. CONCLUSIONS: Sildenafil is an efficacious and well-tolerated treatment for ED in elderly men. PMID- 11213275 TI - Infections in nursing homes: assessing quality of care. AB - BACKGROUND: Each year more than 25% of nursing home patients are taken to the hospital emergency room or hospitalized for the evaluation and treatment of infections. These transfers may have an adverse impact on the quality and the cost of patient care. METHODS: Using both Medicare and Medicaid records from a sample of dually eligible elderly people in Ohio, we identified patients receiving antibiotic prescriptions in the nursing home and measured the frequency of nursing home physician visits and the hospital transfer rate. RESULTS: Among the study sample (N = 1306), two thirds experienced a total of 3685 episodes of infections. Just under 5% of the sample were hospitalized as a result of the infection. In one third of the episodes, physicians saw the resident in person within 5 days (before or after) of the initiation of the medication. The hospital transfer rate was slightly higher (7% vs 3.5%) for those patients directly evaluated by a physician before receiving the prescription. CONCLUSIONS: A majority of prescriptions were written without direct physician examination, raising key questions about practice patterns and the effect on patient care and costs. PMID- 11213276 TI - Aging-related growth hormone (GH) decrease is a selective hypothalamic GH releasing hormone pulse amplitude mediated phenomenon. AB - BACKGROUND: Aging is accompanied by declining growth hormone (GH) and insulin like growth factor-I (IGF-I) levels. The neuroendocrine mechanisms of this decline have been studied previously, but the interpretation of the data was confounded by the imprecision in GH measurements and by the intervening variables of altered body composition and decreased gonadal steroid milieu in the elderly subjects of both sexes. METHODS: To study the contribution of aging per se, we evaluated discrete parameters of GH pulsatility in young (n = 8 women, n = 8 men) and elderly (n = 11 women, in 10 men) subjects closely matched for body mass index. Blood samples for GH were obtained every 10 minutes for 24 hours. Plasma GH was measured by a sensitive chemiluminescent assay. GH pulsatility was assessed using cluster analysis. RESULTS: The elderly subjects had plasma IGF-I levels and integrated GH concentrations that were 32% to -56% of their sex matched younger counterparts. The age-associated attenuation in GH was due to a decrease in GH pulse amplitude, whereas pulse frequency and nadir levels were unchanged. The majority of the young subjects (81%) reached their peak GH during the "lights off" period, whereas the majority of the elderly subjects (62%) peaked during the "lights on" period (p = .01). CONCLUSIONS: We conclude that aging in both sexes is accompanied by profound decreases in GH output and in plasma IGF-I concentrations. This effect is separate from the alterations in body mass index that accompany the normal aging process. Attenuation of GH output associated with aging is related solely to the lower GH and, by inference, GH releasing hormone (GHRH) pulse amplitude. PMID- 11213277 TI - Genetic and phenotypic markers among centenarians. PMID- 11213278 TI - What do the serum proteins tell us about our elderly patients? PMID- 11213279 TI - Longevity and the epsilon2 allele of apolipoprotein E: the Finnish Centenarians Study. AB - BACKGROUND: Whether and which genetic factors affect human longevity is unclear. This study assesses the association between the epsilon2 allele of apolipoprotein E (APOE), a putative longevity gene, and extremely old age. METHODS: This study is based on all centenarians living in Finland in 1991. Subjects were 179 persons (28 men and 151 women) aged 100 years and older (response rate, 97%). RESULTS: The percentages of epsilon2-allele carriers in persons aged 100 to 101, 102 to 103, and 104 years and older were 9% (10/117), 21% (9/42), and 25% (5/20; gender adjusted p for trend = .01), respectively. The effect was particularly strong in women: 8% (8/100), 18% (6/33), and 28% (5/18; p for trend = .01) by age group, respectively. Low cell numbers prevented clear conclusions being drawn for men. Seventeen percent (30/179) of the adult Finnish population were carriers of the epsilon4 allele, a figure lower than expected, and stable by age group. CONCLUSIONS: Carriers of the epsilon2 allele of APOE might be predisposed to reach extremely old age. PMID- 11213280 TI - Serum insulin-like growth factor-1 in centenarians: implications of IGF-1 as a rapid turnover protein. AB - BACKGROUND: It is well documented that serum insulin-like growth factor 1 (IGF-1) levels as well as growth hormone secretion decline with advancing age. Low levels of IGF-1 are shown to be associated with low activity of growth hormone, low lean mass, and high body fat mass; however, in the elderly, the relationship has not been confirmed. METHODS: We studied serum IGF-1 levels in 49 centenarians, who are at the ultimate stage of physiological senescence, and investigated the possible relationship between IGF-1 and body mass index, lipid parameters, nutritional indices, physical and cognitive function, and frequency of hip fracture. As nutritional indices, serum levels of albumin, prealbumin, transferrin, and retinol binding protein were measured. Cognitive function of the centenarians was assessed by clinical dementia rating. RESULTS: In the centenarians, the mean levels of IGF-1 were relatively low, indicating that there is an age-associated decline in IGF-1 even in the extremely old age. We demonstrated a strong association of IGF-1 with prealbumin and retinol binding protein (r2 = .192, .195, respectively); however, there was no association with albumin, transferrin, or body mass index. Interestingly, centenarians with lower IGF-1 levels had a higher prevalence of definitive dementia. CONCLUSIONS: These data suggest that serum IGF-1 levels in the centenarians appeared to reflect their short-term nutritional status as a rapid turnover protein. It is also suggested that low levels of serum IGF-1 may be involved in the progression of dementia in the oldest old. PMID- 11213281 TI - Searching for human longevity genes: the future history of gerontology in the post-genomic era. AB - Over the last 30 years, a number of genetic and environmental factors that lead to decreased length of life have been identified. Unfortunately, much less progress has been achieved in identifying genes associated with longevity that protect from common diseases or slow the aging process. Recent compelling evidence supports a role for important genetic and environmental interactions on longevity in lower organisms. Although less is known in humans, commonality in molecular and biological processes, evolutionary arguments, and epidemiological data would strongly suggest that similar mechanisms also apply. The completion of the Human Genome Project and the rapid innovations in technology will make possible the identification of human longevity-assurance genes. This article reviews such evidence, its implications for the identification of human longevity assurance genes, and the significance of finding longevity genes to human health and disease. PMID- 11213282 TI - Heart failure in the 21st century: a cardiogeriatric syndrome. AB - Chronic heart failure (CHF) is principally a cardiogeriatric syndrome, and it has become a major public health problem in the 21st century due largely to the aging population. Age-related changes throughout the cardiovascular system in combination with the high prevalence of cardiovascular diseases at older age predispose older adults to the development of CHF. Features that distinguish CHF at advanced age from CHF occurring during middle age include an increasing proportion of women, a shift from coronary heart disease to hypertension as the most common etiology, and the high percentage of cases that occur in the setting of preserved left ventricular systolic function. Although the pharmacotherapy of CHF is similar in older and younger patients, the presence of multiple comorbidities in older patients mandates a multidisciplinary approach to care. Manifest CHF is associated with a poor prognosis, especially in elderly persons, and there is an urgent need to develop more effective strategies for the prevention and treatment of this increasingly common disorder to reduce the individual and societal burden of this devastating illness in the decades ahead. PMID- 11213283 TI - Effects of housing relocation on immunocompetence and psychosocial functioning in older adults. AB - BACKGROUND: The psychological and physical response to moderate life stressors among older adults has not been well characterized. This research examines effects of voluntary housing relocation on distress and immune function in healthy older adults as a model for studying the effects of moderate life stress. METHODS: Thirty older adults moving to congregate living facilities were assessed 1 month premove, 2 weeks postmove, and 3 months postmove. Twenty-eight nonmoving control subjects were assessed at similar time points. Subjects completed psychosocial questionnaires and had early morning blood draws in their homes. Blood samples were assayed for natural killer cell cytotoxicity (NKCC), interleukin-6 (IL-6), and IgG antibody titers to the Epstein Barr virus (EBV) viral capsid antigen. RESULTS: Movers demonstrated decreased vigor and elevated thought intrusion 1 month premove and 2 weeks postmove. By the 3-month follow-up, vigor increased, and intrusion decreased to levels commensurate with the controls. Averaged across all time points, movers showed lower NKCC than controls; however, post-hoc analyses indicate that by the 3-month follow-up time point, these differences were no longer significant. There were no differences between groups in IL-6 or in EBV antibody titers. Independent of the effects of group, higher levels of vigor were associated with greater NKCC at all assessments and with lower EBV titers at 2 weeks postmove. CONCLUSIONS: Findings suggest that in general, healthy older adults recover well psychologically from moderate. temporary life stressors such as moving. Whereas movers showed generally lower NKCC than controls, IL-6 and EBV antibody titers appeared not to be strongly affected by the stress of moving. PMID- 11213285 TI - Quinolactacins A, B and C: novel quinolone compounds from Penicillium sp. EPF-6. II. Physico-chemical properties and structure elucidation. AB - Three novel quinolone compounds, quinolactacins A (1), B (2) and C (3), have been found from the fermentation broth of Penicillium sp. EPF-6, a fungus isolated from the larvae of mulberry pyralid (Margaronia pyloalis Welker). The molecular formulas of 1, 2 and 3 were determined to be C16H18N2O2, C15H16N2O2 and C16H18N2O3, respectively by FAB-MS and NMR spectral analyses. The structures of these compounds have a novel quinolone skeleton with a gamma-lactam ring consisting of C12H8N2O2 as the common chromophore. PMID- 11213284 TI - Quinolactacins A, B and C: novel quinolone compounds from Penicillium sp. EPF-6. I. Taxonomy, production, isolation and biological properties. AB - Quinolactacins A (1), B (2) and C (3), novel quinolone antibiotics have been found from the cultured broth of a fungal strain isolated from the larvae of the mulberry pyralid Margaronia pyloalis Welker). The fungal strain, EPF-6 was identified as Penicillium sp. from its morphological characteristics. Quinolactacins were obtained from the culture medium by solvent extraction and chromatographic purification. Compound 1 showed inhibitory activity against tumor necrosis factor (TNF) production induced by murine peritoneal macrophages and macrophage-like J774.1 cells stimulated with lipopolysaccharide (LPS). PMID- 11213286 TI - Biosynthetic intermediates of the tetradehydro cyclic dipeptide albonoursin produced by Streptomyces albulus KO-23. AB - The cell-free extract of an albonoursin-producing strain Streptomyces albulus KO 23 catalyzes the conversion of cyclo(L-Leu-L-Phe) (1) to albonoursin (2). At the early stage of this conversion, two compounds were newly formed prior to albonoursin synthesis in the reaction mixture. These compounds were isolated and identified as (Z)-3-benzylidene-6-isobutyl-2,5-piperazinedione (4) and (Z)-3 benzyl-6-isobutylidene-2,5-piperazinedione (3). The cell-free extract also catalyzed the conversion of compound 3 or 4 to albonoursin. From these results, albonoursin was found to be biosynthesized via these compounds from cyclo(L-Leu-L Phe). These didehydro diketopiperazines exhibited no inhibitory activity toward the first cleavage of sea urchin embryo in contrast to the higher cytotoxicity for albonoursin, indicating that dehydrogenation at alpha,beta-positions of both amino acid residues in diketopiperazines is required for cytotoxicity. PMID- 11213287 TI - Blasticidin A as an inhibitor of aflatoxin production by Aspergillus parasiticus. AB - Blasticidin A, an antibiotic, showed strong inhibitory activity toward aflatoxin production by Aspergillus parasiticus. Its structure was characterized by NMR and chemical degradation experiments as 1, which is a tetramic acid derivative with a highly oxygenated long alkyl chain similar to aflastatin A (2). Absolute configurations of the eight chiral centers at C-4, 6, 31, 32, 33, 34, 35 and 37 of 1 were chemically determined. Blasticidin A almost completely inhibited aflatoxin production at 0.5 microM. PMID- 11213288 TI - Discovery of RWJ-54428 (MC-02,479), a new cephalosporin active against resistant gram-positive bacteria. AB - The discovery of RWJ-54428 (MC-02,479), a new cephalosporin displaying promising activity against sensitive and resistant Gram-positive bacteria, is described. Progressive structural modification from the previously reported 3 phenylthiocephem MC-02,331 afforded an overall increase in potency against MRSA while retaining other key properties such as acceptable solubility and serum binding. Evaluation of the in vitro potency and in vivo efficacy of a series of closely related compounds resulted in selection of RWJ-54428 (MC-02,479) for further studies. PMID- 11213289 TI - Synthesis and activity of analogues of SB-219383: novel potent inhibitors of bacterial tyrosyl tRNA synthetase. AB - SB-219383 is a naturally occurring antibiotic, which acts by inhibition of tyrosyl tRNA synthetase. Semi-synthetic derivatives of SB-219383 were prepared with the objective of elucidating the key features required for inhibition of tyrosyl tRNA synthetase in order to improve the antibacterial activity. Some ester and amide derivatives as well as monocyclic analogues exhibited sub nanomolar inhibitory activity against tyrosyl tRNA synthetase. PMID- 11213290 TI - Aureoquinone, a new protease inhibitor from Aureobasidium sp. PMID- 11213291 TI - Waol B, a new trihydrofuran derivative with cytocidal activity, isolated from Myceliophthora lutea. PMID- 11213292 TI - Biosynthesis of the fungal polyketide antibiotics TMC-151s: origin of the carbon skeleton. PMID- 11213293 TI - Synthesis and antibacterial activities of novel C(3)-aminopyrimidinyl substituted cephalosporins. PMID- 11213295 TI - Laccaridiones A and B, new protease inhibitors from Laccaria amethystea. PMID- 11213294 TI - Reblastatin, a novel benzenoid ansamycin-type cell cycle inhibitor. PMID- 11213296 TI - Argimicin A, a novel anti-cyanobacterial compound produced by an algae-lysing bacterium. PMID- 11213297 TI - Adolf Windaus--Nobel Prize for research on sterols. PMID- 11213298 TI - Reducing the health burden of tobacco use: what's the doctor's role? PMID- 11213299 TI - Residential (inpatient) treatment compared with outpatient treatment for nicotine dependence. AB - OBJECTIVE: To compare smoking abstinence outcomes between smokers treated in a residential (inpatient) program and those treated in an outpatient program to determine if residential treatment was superior to outpatient treatment in smokers with moderate to severe nicotine dependence. PATIENTS AND METHODS: Patients treated in the residential nicotine dependence program at the Mayo Clinic, Rochester, Minn., between May 1, 1992, and January 31, 1996, were selected for this study. Each patient in the residential treatment group (n=146) was matched to 2 patients who received an outpatient nicotine dependence consultation by a trained counselor (n=292). Each patient was matched on age, sex, year seen, number of cigarettes smoked per day, longest previous abstinence, education, and marital status. Abstinence at 6 and 12 months was determined by self-report. For the purposes of analysis, each patient with missing outcome data was considered to be smoking. RESULTS: The 6-month abstinence rates for the residential group compared with the outpatient group were 45% and 26%, respectively (P<.001), and the 12-month abstinence rates were 45% and 23%, respectively (P<.001). After adjusting for matching variables that were not exactly matched (age, baseline number of cigarettes smoked per day, and longest previous abstinence) and the baseline variables, including education, age when started smoking, and degree of nicotine dependence, there was a significant effect of residential treatment on 6- and 12-month abstinence rates (P<.001). Odds ratio of 6-month abstinence in the residential group was 2.74 (95% confidence interval, 1.60-4.71; P<.001) and at 12 months was 3.03 (95% confidence interval, 1.74-5.27; P<.001). CONCLUSION: Residential treatment for tobacco dependence is superior to outpatient treatment in some smokers who are moderately to severely nicotine dependent. PMID- 11213300 TI - Attitudes of Olmsted County, Minnesota, residents about tobacco smoke in restaurants and bars. AB - OBJECTIVE: To determine the attitudes of Olmsted County, Minnesota, adults about environmental tobacco smoke in restaurants, bars, and nightclubs. SUBJECTS AND METHODS: In this population survey,2014 adults were contacted by random digit dial methods between February 28 and May 5, 2000, and asked to participate in a telephone survey; 1224 (61%) consented. RESULTS: For the 57% (95% confidence interval [CI], 54%-60%) of the study population that reported exposure to environmental tobacco smoke, the most frequently reported sites of exposure were restaurants (44% [95% CI, 41%-48%]), work (21% [95% CI, 18%-24%]), and bars (19% [95% CI, 16%-22%]). Seventy-two percent (95% CI, 69%-74%) of respondents said that they would select a smoke-free restaurant over one where smoking is permitted, and 70% (95% CI, 67%-72%) said that they would select a smoke-free bar over one where smoking is permitted. The majority of respondents said that they would not dine out or visit bars or nightclubs more often or less often if all restaurants, bars, and nightclubs were smoke-free. CONCLUSIONS: Olmsted County residents prefer smoke-free restaurants, bars, and nightclubs. PMID- 11213301 TI - Patient satisfaction and discussion of smoking cessation during clinical visits. AB - OBJECTIVE: To learn whether patients who smoke and who receive smoking cessation information during medical office visits were less likely to be satisfied with the smoking cessation help they received than patients who smoke but who did not receive such information. PATIENTS AND METHODS: A total of 3703 current cigarette smokers were identified by a mailing in November 1998 to 163,596 members of 2 Minnesota health plans, and 2714 (77.3%) responses to a 44-item questionnaire were available for analysis. Using hierarchical analysis to control confounding variables, we assessed the relationship between patient-reported smoking cessation support actions at the last physician visit and satisfaction "with the help received from your doctor about quitting smoking." RESULTS: Smokers were very satisfied (12.0%), satisfied (25.3%), neutral (48.6%), and dissatisfied or very dissatisfied (13.5%) with physician help. After controlling for other characteristics, the 1898 patients who reported that they had been asked about tobacco use or advised to quit during the latest visit had 10 percentage point greater satisfaction ratings and 5 percentage point less dissatisfaction than those not reporting such discussions (P<.001). Smokers reporting no interest in quitting at the time of the latest visit also demonstrated greater satisfaction in association with these actions. CONCLUSION: Smoking cessation interventions during physician visits were associated with increased patient satisfaction with their care among those who smoke. This information should reduce concerns of physicians or nurses about providing tobacco cessation assistance to patients during office visits. PMID- 11213302 TI - A free smoking intervention clinic initiated by medical students. AB - OBJECTIVE: To describe a medical student-run smoking intervention clinic, report initial outcomes, and assess medical student competence in smoking intervention counseling. PATIENTS AND METHODS: Volunteer medical students of Mayo Medical School in Rochester, Minn, staffed a free smoking intervention clinic in conjunction with the Salvation Army Free Acute Care Clinic between December 1997 and January 1999. Patients received a comprehensive intervention for smoking that comprised counseling, frequent follow-up contact, and pharmacologic therapy, including bupropion and nicotine replacement. Eighty-eight patients seen during the first 13 months of the clinic's operation and 30 medical student volunteer counselors were included in the study. Patients were contacted via telephone to assess 6-month self-reported smoking abstinence. Medical student counselors completed a self-assessment questionnaire surveying competence before and after working in the clinic. RESULTS: The 6-month self-reported smoking abstinence rate was 18% (95% confidence interval, 11%-28%). Twelve of 14 medical students completing the survey reported improved competence in smoking intervention counseling. CONCLUSIONS: A comprehensive smoking intervention program provided by medical students yielded smoking abstinence rates comparable to other treatment programs. Medical students believed they improved their smoking cessation counseling skills. PMID- 11213303 TI - Doppler hemodynamics of 51 clinically and echocardiographically normal pulmonary valve prostheses. AB - OBJECTIVE: To determine the normal Doppler hemodynamics of various pulmonary valve prostheses (PVPs). PATIENTS AND METHODS: We retrospectively analyzed comprehensive Doppler echocardiographic examinations of 51 patients (mean age, 27.8 years; range, 1-59 years) with PVPs that were normal on clinical and 2 dimensional echocardiographic examinations to establish the normal hemodynamics of various types and sizes of PVPs. The earliest complete postoperative transthoracic echocardiogram was identified for each patient. Doppler examinations were analyzed for peak instantaneous velocity, right ventricular outflow tract velocity, and peak and mean systolic gradient. The frequency of prosthetic regurgitation was also noted. RESULTS: The average +/- SD peak instantaneous velocity for all PVPs was 2.24+/-0.6 m/s, with an average peak systolic gradient of 20.4+/-10.4 mm Hg and an average mean systolic gradient of 11.0+/-5.1 mm Hg. The mean right ventricular outflow tract velocity was 1.0+/-0.2 m/s. Pulmonary homografts were found to have significantly lower peak velocities (average, 1.8+/-0.6 m/s) than all heterografts combined (average, 2.4+/-0.5 m/s; P=.002). Prosthetic regurgitation was more common in pulmonary homografts (88%) than in heterografts combined (29%; P<.001). CONCLUSION: This study establishes the normal range for Doppler hemodynamics of various PVPs, specifically homografts and heterografts, in both pediatric and adult patients. PMID- 11213304 TI - Adrenal hemorrhage: a 25-year experience at the Mayo Clinic. AB - OBJECTIVE: To characterize the clinical course of adrenal hemorrhage (AH) by using a systematic review of the presentation, associated conditions, and outcomes in patients with AH seen at our institution between 1972 and 1997 (a 25 year period). PATIENTS AND METHODS: A computer search of recorded dismissal diagnoses identified 204 patients with a diagnosis of AH, but only 141 fulfilled our study criteria. Their records were analyzed systematically by presentation, bilateral or unilateral hemorrhage, corticosteroid treatment, and survival. RESULTS: AH is a heterogeneous entity that occurs in the postoperative period, in the antiphospholipid-antibody syndrome, in heparin-associated thrombocytopenia, or in the setting of severe physical stress and multiorgan failure. Standard laboratory evaluation is not helpful in establishing the diagnosis. Of the 141 cases of AH, 78 were bilateral, and 63 were unilateral. Corticosteroid treatment in situations of severe stress or sepsis had little effect on outcome (9% vs. 6% survival with and without corticosteroid treatment, respectively). This is in sharp contrast to AH occurring postoperatively (100% vs. 17% survival with or without treatment, respectively) or in the antiphospholipid-antibody syndrome (73% vs. 0% survival, respectively). CONCLUSIONS: A high index of suspicion is required to make a timely diagnosis of AH. Fever and hypotension in the appropriate clinical setting necessitate further investigation. Although the diagnosis of AH is infrequently made while the patient is alive, appropriate imaging techniques are useful for establishing a timely diagnosis. In severe physical stress or sepsis, AH may be a marker of severe, preterminal physiologic stress and poor outcome. PMID- 11213305 TI - Characteristics of patients with upper respiratory tract infection presenting to a walk-in clinic. AB - OBJECTIVE: To profile patients with upper respiratory tract infection (URI) presenting to a walk-in clinic, to quantify their perspectives on the need for antibiotic therapy, and to find out their predictions of future behavior for similar illnesses. PATIENTS AND METHODS: In the spring of 1998, previsit and postvisit questionnaires were distributed at the clinic to patients 18 years of age or older with URI symptoms. RESULTS: Based on 210 completed previsit questionnaires, 161 respondents (77%) had been ill 5 or more days, 200 (95%) had cough, 177 (84%) had phlegm, 132 (63%) had sinus pain, and 79 (38%) had fever. Additionally, 54 patients (26%) reported a history of chronic obstructive pulmonary disease, asthma, or chronic sinusitis, and 37 (18%) were smokers. Most patients were between 18 and 40 years of age. The 210 patients were categorized into 2 groups: those who believed that antibiotics were necessary (157 [75%]) and those who believed antibiotics were unnecessary (53 [25%]). The only statistically significant difference between the 2 groups was in patients with sinus pain: 109 (69%) wanted antibiotics compared with 23 (43%) who did not (P<.001). Of the 210 patients, 130 completed postvisit questionnaires, 129 (99%) of whom reported satisfaction with the clinic visit. All patients who either desired or received antibiotics indicated they would likely seek medical care for future URIs. CONCLUSIONS: The majority of patients with presumed URI presenting to this walk-in clinic expect to receive treatment with antibiotics. Of our 130 study patients, 83 (64%) received antibiotics regardless of their desire for antibiotic treatment. Satisfaction with the office visit was independent of patients' initial beliefs about antibiotics and whether antibiotics were prescribed. PMID- 11213306 TI - Acute and chronic seizures in patients older than 60 years. AB - As the number of older adults continues to increase, the population at risk for neurologic illnesses also rises. Acute and chronic seizures are commonly seen in adults older than 60 years; however, no consensus exists on the best way to diagnose and treat seizures and epilepsy in this age group. Several new medical and surgical therapies are now available for all epilepsy patients, some of which may be especially helpful for older patients. This article reviews the current literature on the diagnosis and management of seizures in older adults. Unique aspects of the epidemiology, etiology, diagnosis, and medical and surgical treatments of acute and chronic seizures in patients older than 60 years are discussed. PMID- 11213307 TI - Narcolepsy: new understanding of irresistible sleep. AB - Recently, low levels of a newly identified neuropeptide, hypocretin 1, were described in the cerebrospinal fluid of patients with narcolepsy. This neurochemical finding furthers our understanding of this enigmatic sleep disorder typically characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, and hypnagogic hallucinations. Narcolepsy appears to be fundamentally related to abnormally regulated rapid eye movement sleep. The diagnosis of this disorder remains challenging because of multiple other conditions that can cause daytime sleepiness and the difficulties in recognizing cataplexy based on patient report. The role of hypocretins in narcolepsy is unclear but intriguing because the cell bodies are restricted to the lateral hypothalamus, a brain region long associated with sleep regulation, with neuronal widespread projections to areas including the locus ceruleus, ventral tegmental area, amygdala, and dorsal raphe. Hypocretins potentially modulate the activity of monoamines and acetylcholine, and therefore their absence leads to the multiple symptoms of narcolepsy. This article reviews the current understanding of the diagnosis and treatment of narcolepsy and discusses the possible implications of the hypocretin discovery. PMID- 11213309 TI - 87-year-old man with macrocytic anemia. PMID- 11213308 TI - Primary esophageal motility disorders. AB - Esophageal motility disorders often manifest with chest pain and dysphagia. Achalasia is a disorder of the lower esophageal sphincter and the smooth musculature of the esophageal body. In achalasia the lower esophageal sphincter typically fails to relax with swallowing, and the esophageal body fails to undergo peristalsis. In contrast to spastic disorders of the esophagus, achalasia can be progressive and cause pronounced morbidity. Pseudoachalasia mimics achalasia in terms of symptoms but can be caused by infectious disorders or malignancy. Treatment for achalasia is nonstandardized and includes medical, endoscopic, and surgical options. Spastic disorders of the esophagus, such as diffuse esophageal spasm and nutcracker esophagus, and nonspecific esophageal motility disorder are benign and nonprogressive, with similar findings on esophageal manometry. Although the exact cause remains unknown, these disorders may represent a manifestation of gastroesophageal reflux disease. Treatment of spastic disorders includes medical and surgical approaches and is aimed at symptomatic relief. PMID- 11213310 TI - Metastatic carcinoma of the breast resembling early gastric carcinoma. AB - We describe a case of gastric metastasis from a lobular carcinoma of the breast in a 45-year-old woman who had undergone a left mastectomy with axillary dissection 7 years earlier. At the current presentation, she had been experiencing progressive epigastric discomfort for 3 months. The initial diagnosis was early gastric carcinoma, diffuse type, based on gastric biopsy findings and ultrasonographic endoscopy. A definitive diagnosis of metastatic breast cancer was confirmed after subtotal gastrectomy of a presumed primary early gastric carcinoma. Although gastrointestinal metastases from breast cancer are not rare, the early stage of the gastric lesion and the absence of further disease dissemination make this case unusual. The onset of gastrointestinal symptoms in a patient with a history of breast carcinoma should prompt the physician to rule out the possibility of gastric metastases. PMID- 11213311 TI - Pulmonary Langerhans cell histiocytosis presenting as a solitary nodule. AB - Solitary pulmonary nodules are an uncommon manifestation of pulmonary Langerhans cell histiocytosis (PLCH). We describe a 45-year-old male cigarette smoker who presented with an asymptomatic solitary pulmonary nodule that showed histologic and immunophenotypic characteristics of PLCH. Twenty-one years after excision of the nodule, at the age of 66 years, he is asymptomatic with a new contralateral lung nodule but no evidence of interstitial disease. The new nodule has remained unchanged after 36 months of observation. This case affirms that PLCH can occasionally cause solitary lesions, which should not be interpreted as a harbinger of interstitial lung disease. Isolated PLCH should be included in the differential diagnosis of unusual solitary pulmonary nodules. PMID- 11213312 TI - Acute renal vein thrombosis, oral contraceptive use, and hyperhomocysteinemia. AB - Oral contraceptive use and hyperhomocysteinemia are considered to be relatively weak risk factors for venous thromboembolism. We report a case of acute renal vein thrombosis, a rare and aggressive form of thromboembolism, that occurred in a 21-year-old woman taking oral contraceptives, who was subsequently found to have marked hyperhomocysteinemia. This case suggests that the oral contraceptive and hyperhomocysteinemia may interact in a synergistic manner in the pathogenesis of thrombosis. In oral contraceptive users who develop venous thrombosis in the absence of other risk factors, clinicians should consider investigations for an underlying prothrombotic biochemical disorder. PMID- 11213313 TI - Reversible galactorrhea and prolactin elevation related to fluoxetine use. AB - Fluoxetine, an antidepressant of the selective serotonin reuptake inhibitor class, may stimulate prolactin release by pituitary lactotrophs. A 71-year-old woman taking estrogen replacement therapy developed galactorrhea after initiation of fluoxetine for depression and was found to have an elevated prolactin level. Fluoxetine was discontinued with resolution of the patient's galactorrhea and normalization of her prolactin level. PMID- 11213314 TI - Endoscopic and histologic diagnosis of Barrett esophagus. AB - Endoscopy plays an important role in the identification, diagnosis, and treatment of Barrett esophagus. Short-segment (<2-3 cm) and traditional long-segment (>2-3 cm) Barrett esophagus are distinguished solely on the length of metaplastic tissue above the esophagogastric junction. The histologic hallmark of intestinal metaplasia is required to confirm diagnosis. Biopsy specimens obtained from tissue of presumed Barrett esophagus or an irregular Z line confirm metaplastic glandular mucosa and permit evaluation of dysplastic or neoplastic changes. In the appropriate clinical setting, the use of adjunctive diagnostic techniques may facilitate the diagnosis of Barrett esophagus and sequelae such as dysplasia. Chromoendoscopy with high-resolution or magnified endoscopy is simple, safe, and desirable for surveillance but requires additional procedural time. The use of light-induced fluorescence endoscopy and light-scattering spectroscopy (i.e., optical biopsy) is appealing for the diagnosis and characterization of suspicious lesions. Adjunctive endoscopic techniques and adherence to a protocol for performing biopsies facilitate the early detection and subsequent surveillance of Barrett esophagus. PMID- 11213315 TI - Pathogenesis of gastroesophageal reflux and Barrett esophagus. AB - Barrett esophagus is a metaplastic condition that affects the lower esophagus and is a complication of gastroesophageal reflux disease (GERD). Under normal circumstances, the reflux of gastric contents into the esophagus is prevented by a complex barrier at the esophagogastric junction. Dysfunction of the lower esophageal sphincter and the presence of a hiatal hernia lead to failure of this barrier. Esophageal mucosal damage results from the chronic exposure of the esophageal mucosa to gastroduodenal contents and the lack of an effective mucosal defense. This article is an overview of the dysfunction of the esophagogastric junction that leads to GERD. The role of the contents of the reflux and that of Helicobacter pylori infection in the pathogenesis of Barrett esophagus are also summarized. PMID- 11213316 TI - Single subject research designs for disability research. AB - PURPOSE: The objective of this article is to offer an overview of single subject designs and provide clinicians with information regarding the components of single subject designs and how they can be used in clinical and other rehabilitation environments. METHOD/RESULT: Three basic designs in single subject research are presented, with corresponding examples illustrating each design. A review of visual and statistical analysis techniques commonly used in single subject designs is provided, and the advantages and limitations of each are noted. CONCLUSION: Single subject designs are ideally suited for research in the rehabilitation practice environment. If properly applied, these designs can help establish the efficacy of rehabilitation practice and contribute to rehabilitation science. PMID- 11213317 TI - The paradox of changing the service delivery system in the field of rehabilitation. PMID- 11213318 TI - Commentary on: Community-based service delivery in rehabilitation: the promise and the paradox. PMID- 11213319 TI - Community based service delivery: power and pathology: or, social rehabilitation is still a 'commie plot'. AB - Service delivery in the broad field of rehabilitation has been declining in quantity and quality for people with disabilities, the dispossessed, and others. The context, that is, our communities, has similarly been weakened. Meanwhile, the world's resources and wealth and talent flow freely up the hierarchies to the powers-that-be, the wealthy and the elite. In turn, these powerful people regard social action efforts to redress the underlying social, economic, and political imbalances as a 'Commie plot'. More, not less, social rehabilitation is needed to make human communities fit again. PMID- 11213320 TI - Commentary on 'community based service delivery in rehabilitation: the promise and the paradox' by Kendall, Buys and Larner. PMID- 11213321 TI - Every solution has a problem. PMID- 11213322 TI - Stroke rehabilitation: application and analysis of the modified Barthel index in an Arab community. AB - PURPOSE: The primary aim was to provide experience with a functional evaluation instrument (modified Barthel index MBI) that assures the quality of work and identify its deficiencies, familiarize our staff with the feasibility of its application on our local inpatients and educate our personnel in the field of stroke rehabilitation. The secondary aim was to collect data that are measurable and reproducible, identify specific local factors that adversely affect outcomes and serve as a feedback system to our national organizations. METHODS: In this prospective/retrospective study we evaluated 80 hemiplegic patients with completed stroke, admitted to hospital during the year 1989 1990. They were assessed by a neurologist, physiatrist and physiotherapist on admission and discharge using the MBI. All patients received comprehensive inpatient rehabilitation. The study was interrupted at the beginning of the Gulf crisis. However, the data were revived and retrospectively studied in the year 1994-1995. RESULTS: The MBI proved to be fully acceptable and easily applicable in our community. The rehabilitation staff became rapidly familiarized with its application and the reproduction of its data. The goals of rehabilitation were achieved through the reduction in the number of individuals in the more severe MBI scores and the increase in the number of individuals in the less severe ones. Significant improvements occurred in dressing of the upper and lower body, washing, grooming, care of perineum, transfer chair, toilet and walking on a level of 50 yards (p < or = 0.0005). CONCLUSIONS: We conclude that MBI is simple, convenient, efficient, gives exact and accurate information about daily activities and ambulation and could be used in inpatient follow up sittings, in the Arab and culturally similar Middle East countries. PMID- 11213323 TI - Disability awareness training for disability professionals. AB - PURPOSE: This article describes work at the Virginia School of the Deaf and Blind in Hampton, Virginia, USA. Disability sensitivity training in businesses and government organizations has become a more important activity in the United States since the Americans with Disability Act (ADA) of 1992 was published. That act of the US Congress required organizations to hire and make reasonable accommodations for the disabled. ISSUE: Lack of sensitivity or awareness of the plight of the disabled in business and government continues to be a distinct problem requiring attitude changes and training, but this problem can become acute even for professionals in organizations dedicated to the care and education of the disabled. CONCLUSION: Professionals tend to become inured to the hardships of others and lose sight of the need for both verbal and non-verbal sensitivity in the workplace. PMID- 11213324 TI - Work profile and functional capacity of formwork carpenters at construction sites. AB - PURPOSE: This study established a work profile and functional capacity for formwork carpenters (FCs) working at construction sites. METHOD: Thirty male FCs aged 19-45 were recruited by convenient sampling from the construction training centres. All FCs participated in an interview/questionnaire and a standardized functional capacity evaluation (FCE) using the Baltimore Therapeutic Equipment Primus (BTE Primus) and Valpar Component Work Sample (VALPAR19). Thirty male adults (office workers) aged 19-45 participated in the exact FCE for comparison. RESULTS: The results of the questionnaire indicated that the job demands of formwork carpenters were frequent lifting (46.7%), carrying (50.0%) and handling (60.0%). Significantly higher lifting and carrying capacities were revealed among the FCs, but not in their isometric strengths and the endurance of the upper limbs (chi2 = 6.48, df = 2, p < 0.05). CONCLUSIONS: The dynamic and repetitive sub-maximal nature of the work of formwork carpentry induced an elevation of job specific lifting and carrying capacities among the FCs. The job and functional capacity profiles would be useful for formulating guidelines for the rehabilitation of injured workers and the training of new workers in the trade. PMID- 11213326 TI - Vive la difference. PMID- 11213325 TI - Heart of the matter. PMID- 11213327 TI - Women in dentistry. PMID- 11213328 TI - Dental strategy. PMID- 11213329 TI - Routine check-ups. PMID- 11213331 TI - Cartoon cover. PMID- 11213330 TI - Oral cancer knowledge. PMID- 11213332 TI - Tooth notations. PMID- 11213333 TI - Special care dentistry. PMID- 11213334 TI - Oral temazepam. PMID- 11213335 TI - Antibiotic cover. PMID- 11213336 TI - Dentists register on the Internet. PMID- 11213337 TI - Factors associated with oral health: a multivariate analysis of results from the 1998 Adult Dental Health survey. PMID- 11213338 TI - Clasp design. PMID- 11213339 TI - Introducing safety syringes into a UK dental school--a controlled study. AB - AIM: How an appropriate safety syringe was chosen, how the change-over to it was achieved and what outcome measures were used to measure the effectiveness of this change. INTRODUCTION: One third of all reported sharps injuries in dental practice are due to the use of non disposable dental syringes with most injuries being sustained during removal and disposal of the disposable needle from the non disposable syringe. METHOD: After evaluation of all available disposable safety syringes they were introduced into a dental school after appropriate education of all staff and students. Risk management provided data on all reported needle stick injuries in the dental school and a control unit using non disposable syringes for a period of two years. RESULTS: Avoidable needle stick injuries reduced from an average of 11.8 to 0 injuries per 1,000,000 hours worked per year as compared with a control unit who reduced their frequency from 26 to 20 injuries per 1,000,000 hours worked. The cost of safety syringes is comparable to non-disposable syringes but the reduction in cost of management of needle stick injuries including the psychological effects are significant. CONCLUSION: Education plays a vitally important role in the effective implementation of the change to safety syringes which is advocated for all dentists. PMID- 11213340 TI - The provision of dental implants in the National Health Service Hospital dental services--a national questionnaire. AB - OBJECTIVE: To assess the activity of consultants in restorative dentistry in the United Kingdom in the provision of osseointegrated dental implants within the National Health Service Hospital service and to evaluate their attitudes concerning the relevant medical and oral factors considered in patient selection for implant treatment. DESIGN/SETTING: Anonymous postal questionnaire in the United Kingdom. SUBJECTS: Consultants in restorative dentistry. RESULTS: Out of the sample of 145, 109 consultants (75%) completed the questionnaire in 1999. 54 of the 109 consultants (49.5%) are involved in the provision of osseointegrated implant treatment, treating an average of 29 cases/year (range 2-150). However, over one third of the respondents treated 10 or less cases/year. 89% worked with oral surgeons as an implant team. 68% used Branemark (Nobel Biocare) implants as their main system. The majority of consultants felt that smoking, psychoses and previous irradiation were the most important medical factors that contra indicated implant retained restorations whilst untreated periodontitis, poor oral hygiene and uncontrolled caries were the most important oral contra-indications. Many centres were experiencing significant problems with the funding of implant treatment with one centre receiving no funding. The implications for patient care and specialist training are discussed. CONCLUSIONS: There is a marked variation in the number of patients treated with endosseous dental implants within the United Kingdom National Health Service hospitals. Many consultants treat 10 or fewer patients each year. In the main, there is agreement about the factors that contra-indicate implant treatment; these are in line with national guidelines. PMID- 11213342 TI - The in vitro colony assay: a predictor of clinical outcome. AB - PURPOSE: To determine the predictive power of an in vitro colony assay on the clinical normal-tissue complication rate. MATERIAL AND METHODS: Primary skin fibroblasts from 88 individuals were generated from the skin biopsies of patients who received a standardized radiotherapy. Tissue was cultured for three to six passages, irradiated with doses between 1 and 8 Gy under defined conditions, seeded and finally the colonies were stained and counted after 10-14 days. The survival curves were fitted by the L-Q model and the SF2, alpha/beta and plating efficiency were calculated. RESULTS: The parameters SF2 and plating efficiency were stable throughout the 4-year test period. Intra-individual differences between repeated experiments were significantly lower than inter-individual test results. For the observed acute skin and late normal-tissue reactions other than skin the in vitro parameter SF2 correlated significantly (p<0.005). For late skin reactions this correlation was not found. DISCUSSION: In contrast to other publications, a clear correlation was found between the in vitro test results and clinically observed early reactions. The lack of correlation for late skin reactions suggests that the combination of intrinsic radiation sensitivity and exogenous factors may alter the clinically observed reaction of certain tissues to a different extent. PMID- 11213341 TI - Radiation sensitivity and apoptosis in human lymphoma cells. AB - PURPOSE: The impact ofapoptosis on radiation-induced eradication of clonogenic tumour cells is uncertain. The aim was to analyse the relationship of different functional stages during the apoptotic process to cell death and clonogenic cell eradication. MATERIALS AND METHODS: Apoptosis in Jurkat T-cells was studied by morphology, light scatter and caspase activation. Mitochondrial integrity was determined by the mitochondrial membrane potential (delta(phi)m). Cell death was quantified using propidium iodide exclusion. Clonogenic cell death was determined using a dilution survival assay. The influence of Bcl-2 was tested using a Bcl-2 transfected Jurkat clone. RESULTS: Irradiation induced profound apoptosis within 48 h associated with caspase activation and breakdown of delta(phi)m. Inhibition of caspases abrogated the apoptotic morphology with no influence on breakdown of delta(phi)m and survival. Over-expression of Bcl-2 abrogated all hallmarks of apoptosis; delayed cell death, however, had no influence on clonogenic survival after irradiation. CONCLUSION: Based on Bcl-2 as a positional marker, radiation induced apoptosis can be divided into two stages: the initiation/decision phase, characterized by a breakdown of the mitochondrial membrane potential, and the execution phase, characterized by caspase activation. The execution phase had no influence on survival, whereas the initiation/decision phase controls immediate survival. However, abrogation of both phases did not influence radiation sensitivity. PMID- 11213343 TI - A cluster of childhood leukaemias near two neighbouring nuclear installations in Northern Germany: prevalence of chromosomal aberrations in peripheral blood lymphocytes. AB - PURPOSE: Between 1990 and 1991 a leukaemia cluster was observed in children living close to the combined site of a nuclear power plant and a nuclear research facility in Elbmarsch, a region in Lower Saxony (Germany). We aim to investigate the prevalence of presumably radiation-induced chromosomal aberrations in peripheral blood lymphocytes of children in Elbmarsch and children of a control region in order to find out whether there was an uncontrolled release of radioactive material which resulted in a substantial exposure. MATERIALS AND METHODS: The frequency of dicentric and ring chromosomes in lymphocytes of the peripheral blood in 42 children in Elbmarsch and 30 children in Plon was investigated. Children in both groups had been permanent residents of the study area. RESULTS: The mean frequency of dicentric and ring chromosomes in Elbmarsch was 14/32580 cells (=0.430 x 10(-3); 95% CI 0.24-0.70 x 10(-3) cells), and in Plon it was 17/24065 cells (=0.706 x 10(-3); 95% CI 0.42-1.10 x 10(-3) cells). CONCLUSIONS: No difference in the frequency of dicentric and ring chromosomes was observed between children in Elbmarsch living close to a combined site of a nuclear power plant and a nuclear research facility and children living in the control area Plon. The power of the study to detect a threefold or higher increase in the aberration frequency was at least 0.86. PMID- 11213344 TI - Physical heights of children with prolonged low dose-rate gamma-radiation exposure in radiocontaminated buildings. AB - PURPOSE: To evaluate low dose-rate radiation effects on the physical heights of children staying in apartments with 60Co-contaminated steel construction. MATERIALS AND METHODS: Children who once resided in radiocontaminated apartments since early 1983 were examined for height and body weight status from age 1 month to 18 years and before they moved out of the apartments. The physical heights and body weights of 21 898 age- and sex-matched non-exposed children from a nationwide school surveillance in 1997-98 were taken as controls. The physical height data were shown as height percentiles (HP) compared with reference children and age-specific relative height differences (RHD). RESULTS: HP and RHD in 48 exposed boys and 37 girls were analysed using generalized estimating equations (GEE), which accounted for multiple measurements and correlation between these measurements in the same individuals during this period. After adjusting for effects from parental heights and body mass index (BMI), clear dose related decreases in HP and RHD were observed in the exposed boys with a cumulative exposure > 60 mSv. CONCLUSIONS: Prolonged low dose-rate y-radiation exposure was associated with adverse effects on the physical heights of growing boys, but were less apparent in the exposed girls. PMID- 11213345 TI - Cellular effects of high-intensity focused continuous wave ultrasound alone and in combination with X-rays. AB - PURPOSE: To investigate the cellular effects of 1.1 MHz high-intensity focused continuous wave (CW) ultrasound alone and in combination with X-rays. MATERIALS AND METHODS: V79 cells were exposed to ultrasound of different intensities for 30s (non-hyperthermic conditions). In the combined treatments, cells were exposed to ultrasound (63 W/cm2) either before or after 2 Gy X-irradiation. Cellular effects studied were clonogenic survival, DNA strand breaks (pulsed-field gel electrophoresis, DNA precipitation assay) and membrane integrity (morphological analysis). RESULTS: With increasing ultrasound intensity, cell survival decreased in a dose-dependent manner as the induction of DNA strand breaks, the fraction of cells with lost membrane integrity and cell lysis increased. In the treatments with combined exposures, the regimen with X-rays before ultrasound had a nearly additive effect on cell kill, whereas the reverse regimen with ultrasound exposure before X-irradiation resulted in a synergistic effect (p<0.012). CONCLUSIONS: High-intensity focused CW ultrasound induces an intensity-dependent reduction in clonogenic survival in V79 cells, which seems to depend on both DNA and membrane damage. Combined exposures of ultrasound and X-rays resulted in a synergistic reduction in cell survival when cells were exposed to ultrasound before X-rays but not for the reverse regimen. Thus, a larger fraction of the repairable sublethal cell damage induced by an initial ultrasound exposure was rendered non-repairable by a subsequent X-ray exposure than if the reverse treatment order was used. PMID- 11213346 TI - Threshold effect for teratogenic risk of radiation depends on dose-rate and p53 dependent apoptosis. AB - PURPOSE: To obtain evidence that the p53 gene is indispensable for reduction of high teratogenic risk of radiation at a high dose-rate to zero risk by lowering the dose-rate. MATERIALS AND METHODS: Wild-type p53(+/+), heterozygous p53(+/-) and null p53(-/-) mice were exposed to gamma-rays at high or low dose-rates during days 9.5-10.5 of gestation. The incidence of malformations and prenatal deaths was studied. Frequencies of cells dying by apoptosis were measured during or after protracted irradiation. RESULTS: After irradiation with 2 Gy, the frequency of apoptotic cells increased to 20% for p53(+/+) mice and did not increase at all for p53(-/-) mice. For p53(+/+) mice, 2 Gy y-rays induced 70% malformations when given at 1.06 Gy/min, but no malformations above the control when given at 1.2 mGy/min. In contrast, after irradiation of p53(-/-) foetuses with 2 Gy at 1.2mGy/min, the incidence of malformations increased 12% above control levels. CONCLUSION: Foetal irradiation with 2 Gy at 1.2 mGy/min was not teratogenic for p53(+/+) mice but teratogenic for p53(-/-) mice. This indicates that the p53 gene is indispensable for a threshold effect in the risk of radiation at low doses or dose-rates. PMID- 11213347 TI - Susceptibility to radiation-induced leukaemia/lymphoma is genetically separable from sensitivity to radiation-induced genomic instability. AB - PURPOSE: To determine whether there is a relationship between the genetics underlying the susceptibility to radiation-induced leukaemia in CBA/H (acute myeloid leukaemia, AML) and C57BL/6 (thymic lymphoma, TL) mice, and the genetics underlying the sensitivity of CBA/H (sensitive) and C57BL/6 (resistant) mice to radiation-induced chromosomal instability. MATERIALS AND METHODS: CBA/H, (CBA/H x C57BL/6)F1, F1 x CBA/H, F1 x C57BL/6 and F1 x F1 mice were exposed to a single acute dose of 3.0 Gy X-rays. AML and TL were diagnosed over the subsequent 30 months. RESULTS: There was no statistically significant difference in the incidence of AML in F1, F1 x F1, F1 x CBA/H and F1 x C57BL/6 mice, which was approximately 50% that in CBA/H mice. AML susceptibility is therefore a dominant polygenic trait, and both susceptibility and resistance (variable penetrance) CBA/H and C57BL/6 loci are involved. The incidence of TL in the FM and F1 x CBA/H mice was negligible, indicating that TL susceptibility is a recessive trait. As the TL incidence in the F1 x C57BL/6 mice was about half that in C57BL/6 mice, one recessive locus is probably involved. CONCLUSIONS: AML susceptibility in CBA/H mice is a dominant trait in contrast to the recessive inheritance of CBA/H sensitivity to radiation-induced chromosomal instability. TL-susceptibility in C57BL/6 is a recessive trait in contrast to the dominant inheritance of C57BL/6 resistance to radiation-induced chromosomal instability. PMID- 11213348 TI - Oncoprotein expression in human breast epithelial cells transformed by high-LET radiation. AB - PURPOSE: The aim of the present work was to analyze the expression of oncoproteins that are frequently altered in breast cancer with specific phenotypic stages in the neoplastic process. MATERIALS AND METHODS: Expression of c-myc, c-jun, c-Ha-ras and the tumor suppressor gene p53 oncoproteins were examined by immunohistochemical staining coupled with confocal microscopy in transformed and tumorigenic human breast epithelial cells induced by high-LET alpha-particles (150 kcV/microm). RESULTS: MCF-10F cells, irradiated with single and double doses of 60 cGy alpha-particles and subsequently treated with cstrogen, showed gradual phenotypic changes including altered morphology, increased cell proliferation relative to control, anchorage-independent growth, invasive capabilities and tumorigenicity in nude mice. MCF-10F cells irradiated with a second dose of 60 cGy alpha-particles after estrogen treatment (60 cGy+ E/60 cGy+E) showed tumorigenicity both in SCII) and nude mice. Alterations in the protein expression of several oncogenes including c-myc, c-jun, c-Ha-ras and the tumor suppressor gene p53 were detected in alpha-particle-irradiated cells and in those cells subsequently cultured in the presence of estrogen. The expression level of these oncoproteins correlated with the progressive nature of the neoplastic process. CONCLUSION: These studies suggest that overexpression of several oncoproteins is important in the neoplastic transformation of human breast epithelial cells induced by high-LET radiation. In addition, use of endocrine factors such as estrogen allows the examination of various aspects of protein expression providing the basis for understanding the complex interactions of hormones and genes. PMID- 11213350 TI - Mutagenic effects of 5-formyluracil on a plasmid vector during replication in Escherichia coli. AB - PURPOSE: 5-Formyluracil (5-foU) is a major derivative of thymine produced in DNA by ionizing radiation and various chemical oxidants. It has been previously shown that 5-foU in template DNA directs misincorporation of nucleotides by DNA polymerases during in vitro DNA synthesis. The present experiments were designed to understand the biological effects of5-foU in vivo. MATERIALS AND METHODS: The modified base was incorporated site-specifically into the recognition site of restriction endonuclease SalI (5'-GTCGAC) or AflII (5'-CTTAAG) in vector plasmid pSVK3 and introduced the plasmid into Escherichia coli. RESULTS: When the plasmids were replicated in E. coli, 5-foU caused mutations at the target sites. The induced mutation frequencies were 0.038-0.049%. Sequence analysis revealed that 5-foU preferentially caused T:A-->C:G and T:A-->A:T base substitutions and 1 deletions at the 5-foU site. 5-FoU also caused mutations at sites near the 5 foU. The alkA mutation did not affect the frequency of mutations in 5-foU containing plasmids. CONCLUSIONS: The present experiments demonstrated that 5 formyluracil in DNA caused mutations in E. coli. PMID- 11213349 TI - Induction of osteosarcoma and acute myeloid leukaemia in CBA/H mice by the alpha emitting nuclides, uranium-233, plutonium-239 and amercium-241. AB - PURPOSE: To compare tumour induction in CBA/H mice, principally osteosarcoma and acute myeloid leukaemia, resulting from exposure to the alpha-emitting nuclides, uranium-233, plutonium-239 and americium-241, and to relate differences between the three nuclides to the pattern of dose delivery within tissues. MATERIALS AND METHODS: Each nuclide was administered intraperitoneally in citrate solution to three groups of adult male CBA/H mice at levels of activity which gave estimated life-time average skeletal doses of about 0.25-0.3 Gy, 0.5-1 Gy and 1-2 Gy. Animals were carefully monitored and sacrificed as soon as they showed signs of ill health; tumours were identified by standard histopathological techniques. RESULTS: Statistical modelling by Cox regression showed that, considering all three nuclides together, there was a highly significant increase in risk of death from osteosarcoma or myeloid leukaemia with increasing dose rate. For osteosarcoma, the effect was significantly greater for 239Pu than 241Am, while separate analysis for 233U showed no significant increase with increasing dose rate. For example, the increase in relative risk of death from osteosarcoma for an increase in life-time average dose rate to bone of 1 mGyd(-1) was 4.2 (2.7 6.5) for 239Pu, 2.3 (1.4-3.4) for 241Am and 1.1 (0.4-3.1) for 233U. For myeloid leukaemia, there was no significant difference between 239Pu and 241Am in the effect of dose rate. The increase in relative risk from myeloid leukaemia for an increase in average dose rate of 1 mGyd(-1) was 1.8 (1.1-2.8) for 239Pu, 2.0 (1.4 2.9) for 241Am and 1.5 (0.8-2.7) for 233U. Significant increases in renal and hepatic carcinomas were also recorded in animals exposed to 233U and 241Am, respectively. Studies of the distribution of the nuclides within the skeleton, published separately, have shown differences in their retention in individual bones and within bone. The proportions of decays occurring near to endosteal bone surfaces and throughout bone marrow were in the order: 239Pu> 241Am>233U. CONCLUSIONS: For osteosarcoma, the relative effectiveness of the nuclides in terms of average bone dose, in the order 239Pu>241Am>233U, is consistent with the proportion of dose delivered near to endosteal surfaces. For myeloid leukaemia, the greater effectiveness of 239Pu and 241Am than 233U is consistent with their accumulation in marrow. PMID- 11213351 TI - Analysis of Ar-ion and X-ray-induced chromatin breakage and repair in V79 plateau phase cells by the premature chromosome condensation technique. AB - PURPOSE: The premature chromosome condensation technique has been used to compare chromatin breakage and repair in noncycling V79 cells following high and low LET radiation. MATERIALS AND METHODS: Plateau-phase V79 cells were exposed to graded doses of low energy Ar ions (LET 1233 keV/microm) and X-rays. Cells were fused to mitotic V79 cells immediately after exposure to examine initial chromatin breakage or after various time intervals of post-irradiation incubation to investigate the kinetics of chromatin break rejoining as well as the fraction of unrejoined fragments. RESULTS AND CONCLUSIONS: For both radiation qualities an average initial number of about 2.4 excess PCC fragments per cell per Gy was found increasing linearly with dose. The distributions of PCC chromosomes plus excess fragments among cells followed Poisson statistics after X-ray irradiation, while an overdispersion of the frequencies was observed after Ar-irradiation indicating that a single particle traversal through a cell nucleus can produce multiple chromatin lesions. Moreover, for both radiation types the rejoining of excess fragments has been examined. Both data sets could be fitted well to first order kinetics with a single component. Despite similar rates of rejoining cellular repair was noticeably less effective for Ar ions than for X-rays. While after 10 h of post-irradiation incubation 60% of Ar ion induced excess fragments remained unrejoined, only 14% of X-ray-induced lesions were not rejoined. Furthermore, comparison of the residual number of excess PCC fragments with recently published data on the yield of chromosome aberrations in first post irradiation metaphases shows that for both radiation types more aberrations are detected in interphase than in metaphase cells. Yet, for comparable doses this difference is more pronounced for Ar ions indicating that scoring of high LET induced aberrations in metaphase cells might result in a significant underestimation of the produced damage. PMID- 11213352 TI - In utero radiation-induced apoptosis and p53 gene expression in the developing rat brain. AB - PURPOSE: This study addressed the question of the role of the p53 gene in prenatal low-dose radiation-induced apoptosis in the neuroepithelium, in an effort to elucidate molecular mechanisms involved in the extreme radiosensitivity of the developing brain. MATERIALS AND METHODS: Pregnant Wistar rats were exposed to a single dose of 10, 20 or 40 cGy of X-rays on day 15 or 17 of gestation. Animals were sacrificed 4 or 24h after exposure. Apoptosis was studied by gel electrophoresis of isolated DNA and in situ by the TUNEL reaction. Expression of the p53 gene was studied by immunocytochemistry and Western analysis, as well as Northern analysis, for the detection of the protein and mRNA respectively. RESULTS: In utero low-dose irradiation led to apoptosis and an increase of p53 gene expression in the developing rat brain. Apoptotic as well as p53 immunopositive cells were detected among proliferating, migratory and post mitotic neurones in the developing neuroepithelium following prenatal irradiation, even after only l0 cGy. In addition to the p53 protein, p53 mRNA brain levels were also increased following prenatal irradiation. CONCLUSIONS: Low dose prenatal irradiation of the developing brain led to p53 induction and cell death by apoptosis. PMID- 11213353 TI - In utero radiation-induced changes in growth factor levels in the developing rat brain. AB - PURPOSE: To investigate the role of growth factors in the compensatory response to radiation injury during development of the brain. Levels of gene expression in the embryonic rat brain were assessed for IGF-I, IGF-II, BDNF and NT-3. MATERIALS AND METHODS: Pregnant Wistar rats were exposed to a single dose of 10, 20 or 40 cGy X-rays on day 15 or 17 of gestation. Animals were sacrificed 4 or 24 h after exposure. IGF-I, BDNF and NT-3 proteins were detected by immunocytochemistry, while IGF-I and IGF-II mRNA by in situ hybridization, and Northern analysis respectively. RESULTS: In utero low dose X-irradiation led to a decrease in IGF-I gene expression and a compensatory increase in the expression of IGF-II, BDNF and NT-3 in the developing rat brain. IGF-I, BDNF and NT-3 immunopositive cells were detected among proliferating, migratory and post-mitotic neurones in the developing neuroepithelium. CONCLUSIONS: Low dose prenatal irradiation of the developing brain results in down-regulation of IGF-I, which could lead to cell death by apoptosis. On the other hand, IGF-II, BDNF and NT-3 gene expression is increased following irradiation, possibly as a compensatory mechanism. PMID- 11213354 TI - Inflammatory response to abdominal irradiation stimulates hemopoiesis. AB - PURPOSE: The connection between inflammation and hemopoiesis was studied in the context of abdominal irradiation. MATERIALS AND METHODS: Male C57BL6/J mice received localized irradiation of 20 Gy either to 70% of the liver or to the intestine (most of ileum and caecum). RESULTS: Irradiation of liver induced a rapid increase in intercellular adhesion molecule-1 mRNA expression in the liver. In serum/plasma, an increase in positive acute phase proteins (serum amyloid-P and fibrinogen) and a decrease in albumin occurred during the second and third week following liver irradiation. Similarly, intestinal irradiation induced an increase in plasma fibrinogen level. A transient elevation in neutrophil and platelet counts was observed that was maximal during the second and third week with similar kinetics for intestinal and liver irradiation. Moreover, intestinal irradiation enhanced hemopoietic progenitors in bone marrow. IL-6, which is known to be an agonist in the regulation of acute phase protein expression as well as hemopoietic cell production, was increased in plasma from intestinal- and liver irradiated mice. Administration of an anti-IL-6 mAb to intestinal-irradiated mice abrogated the elevation of fibrinogen and the increase in hemopoietic progenitors. CONCLUSIONS: Abdominal irradiation provokes an inflammatory response which in turn stimulates hemopoiesis. IL-6 may play a major role in controlling these events. PMID- 11213355 TI - The inhibitory effects of lead on steroidogenesis in MA-10 mouse Leydig tumor cells. AB - Lead is an environmental and occupational pollutant. It has been reported that lead affects the male reproductive system in humans and animals. However, the cellular mechanism of the adverse effect of lead on Leydig cell steroidogenesis remains unknown. To clarify whether lead has a direct effect on Leydig cells and how lead affects Leydig cells, MA-10 cells, a mouse Leydig tumor cell line, were exploited in this study. Lead acetate significantly inhibited hCG- and dbcAMP stimulated progesterone production in MA-10 cells at 2 h. Steroid production stimulated by hCG or dbcAMP were reduced by lead. The mechanism of lead in reducing MA-10 cell steroidogenesis was further investigated. The expression of Steroidogenic Acute Regulatory (StAR) protein and the activities of P450 side chain cleavage (P450scc) and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) enzymes were detected. Cells were treated with dbcAMP, 22R-hydroxycholesterol or pregnenolone alone or in combination with lead acetate ranging from 10(-8) to 10( 5) M for 2 h. The expression of StAR protein stimulated by dbcAMP was suppressed by lead at about 50%. Progesterone productions treated with 22R hydroxycholesterol or pregnenolone were reduced 30-40% in lead-treated MA-10 cells. These data suggest that lead directly inhibited steroidogenesis by decreasing StAR protein expression and the activities of P450scc and 3beta-HSD enzymes with a dose-response trend in MA-10 cells. Moreover, cadmium, a calcium channel blocker, abolished inhibitory effect of lead on MA-10 cell steroid production. This indicates that lead might act on calcium channel to regulate MA 10 cell steroidogenesis. PMID- 11213356 TI - Human chorionic gonadotropin beta-core fragment is directly produced by cancer cells. AB - The present study was undertaken to investigate whether hCG beta-core fragment (hCGbeta cf) was directly produced by cancer cells. Fifteen cell lines, including four choriocarcinoma and five ovarian cancer cell lines, were tested, and immunoreactivity of hCGbeta cf was present in the culture media of five of the cell lines. It was also present in the culture media of Chinese hamster ovary (CHO) cells transfected with hCGbeta gene. In addition to hCGbeta cf, gel chromatography and Western blot analysis of the culture media showed the presence of an hCGbeta cf immunoreactive material with a molecular weight of approximately 40 kDa. In an in vivo study, hCGbeta cf immunoreactivity was detected in the sera of the mice transplanted with NaUCC-3 choriocarcinoma cells, although the ratios of hCGbeta cf/hCG and hCGbeta cf/free hCGbeta were lower than those in the culture medium. Incubation experiments of purified hCGbeta cf in the serum showed no substantial decrease in its values, ruling out the possibility that formation of a macromolecule with serum components may mask hCGbeta cf immunoreactivity in the serum. Taken together, these results indicate that hCGbeta cf immunoreactive materials are directly produced by cancer cells and hCGbeta cf is not a urinary metabolite of hCG or hCGbeta alone. Also, reduced levels of hCGbeta cf in the serum compared with that of intact hCG or free hCGbeta are likely due to its short half-life. PMID- 11213357 TI - Modulation of serotonin transporter function by interleukin-4. AB - Serotonin (5-HT) is an important mediator of interactions between the nervous and immune systems. 5-HT signaling is regulated by the 5-HT transporter (5-HTT), which determines the magnitude and duration of serotonergic responses. Due to this important role, regulation of the 5-HTT by cytokines has been the focus of recent interest. A number of proinflammatory cytokines, including interleukin 1beta, tumor necrosis factor-alpha, and interferon-gamma, have been shown to upregulate the 5-HTT. In the present study we investigated the influence of interleukin-4 (IL-4), which acts as an anti-inflammatory cytokine in the central nervous system, on the 5-HTT. As a model system we used immortalized B lymphocytes, which not only express the 5-HTT, but also allow testing the co modulatory influence of a recently described polymorphism in the 5-HTT gene promoter (5-HTTLPR) that is associated with anxiety- and depression-related behavioral traits. The results show that IL-4 induces a dose-dependent reduction of 5-HT uptake. This effect is preferentially seen in cell lines homozygous for the long, high-activity allele of the 5-HTTLPR. In conclusion, a picture of differential modulation of the 5-HTT by proinflammatory and anti-inflammatory cytokines is emerging, which may represent a fine-tuned mechanism to communicate the state of an immune response to the central nervous system. PMID- 11213358 TI - Influence of estradiol and progesterone on the sensitivity of rat thoracic aorta to noradrenaline. AB - The aim of this study was to investigate the effects of low and high doses of estradiol, and of progesterone on the response to noradrenaline in rat thoracic aorta. Two weeks after bilateral ovariectomy, female rats received a s.c. injection of vehicle (corn oil, 0.1 mL/day), estradiol (10 microg/kg/day or 4 mg/kg/day) and/or progesterone (20 mg/kg/day), for eight days. On the ninth day, the rats were sacrificed and aortic rings, with or without endothelium, were used to generate concentration-response curves to noradrenaline. Aortic rings with intact endothelium from the high-dose (4 mg/kg/day) estradiol group were supersensitive to noradrenaline compared to the vehicle or low-dose (10 microg/kg/day) estradiol groups (pD2 values = 7.86+/-0.09, 7.30+/-0.11 and 7.35+/ 0.04, respectively). Endothelium-intact aortic rings from high-estradiol rats were supersensitive to noradrenaline when compared to vehicle-, progesterone- and progesterone + high-estradiol-treated rats (pD2 values = 7.77+/-0.12, 7.21+/ 0.13, 6.93+/-0.04 and 7.22+/-0.18, respectively). There were no significant differences among the pD2 values for noradrenaline in aortic rings without endothelium. In conclusion, at high but not low doses, estradiol increased the sensitivity to noradrenaline and this was prevented by progesterone. Both of these effects were endothelium-dependent. PMID- 11213359 TI - Effects by doxorubicin on the myocardium are mediated by oxygen free radicals. AB - We hypothesized that doxorubicin (DOX) induces cardiotoxicity of myocardium via oxygen radicals. The present study is aimed at examining the membrane alterations by oxygen radicals generated by DOX in adult rats and cultured neonatal myocytes. Our results showed that DOX 1) decreased beta-adrenoceptor (BAR) density in the cell membrane, 2) increased the membrane permeability of cultured neonatal rat myocytes and 3) altered the ultrastructure of myofibrils and subplasmalemmal actin networks. These effects were reproducible by exogenous hydrogen peroxide. The antioxidant melatonin (MLT) inhibited enzyme leakage and peroxidation in a concentration-dependent manner. It is concluded that DOX induces cardiotoxicity through lipid peroxidation and melatonin is an effective antioxidant against the reactive oxygen intermediates generated by DOX. PMID- 11213360 TI - Magnesium tanshinoate B (MTB) inhibits low density lipoprotein oxidation. AB - Danshen, a Chinese herbal medicine has been widely used for the treatment of cardiovascular diseases. Magnesium tanshinoate B (MTB) is an active compound purified from Danshen. The objective of this study was to investigate the effect of MTB on the susceptibility of low density lipoproteins (LDL) to oxidative modification as well as on the accumulation of lipids in THP-1 derived macrophages. Aliquots of LDL were incubated with copper sulfate in the absence or presence of MTB. The degrees of oxidative modification of LDL were assessed by examining the relative gel electrophoretic mobility, by measuring the amount of thiobarbituric acid reactive substances (TBARS), and by continuous monitoring of the formation of conjugated dienes upon the increase in absorbency at 234 nm. MTB at concentrations of 1-10 microM significantly inhibited oxidative modification of LDL. Such inhibitory effect resulted in a decrease in the uptake of LDL by THP 1 derived macrophages. Taken together, these results clearly demonstrate that MTB inhibits oxidative modification of LDL and hence prevents the uptake of LDL by cultured macrophages. Such effect may be therapeutically relevant in protecting cells from lipid peroxidation in vascular disorders. PMID- 11213361 TI - Effects of nitric oxide on matrix metalloproteinase-2 production by rheumatoid synovial cells. AB - Nitric oxide (NO) is a multifunctional messenger molecule generated from L arginine by a family of enzymes, including nitric oxide synthase (NOS). This study was performed to examine whether NO modulates the production of matrix metalloproteinases (MMPs), which degrade all components of extracellular matrix (ECM), in rheumatoid synovial cells. We investigated the effects of exogenously generated NO by a NO donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP), on the MMPs production by rheumatoid synovial cells. Culture media conditioned by SNAP treated synovial cells were examined by gelatin zymography and immunoblot analysis. Incubation of synovial cells with SNAP resulted in gelatinase A production in a dose-dependent fashion. Furthermore, RT-PCR analysis demonstrated that MMP-2 mRNA expression was induced in SNAP-treated synovial cells. In contrast, SNAP did not influence the production of TIMP-1 and TIMP-2, which preferentially inhibit MMP-2, by rheumatoid synovial cells. Our data indicate that NO could modulate MMP production by rheumatoid synovial cells and therefore contribute to ECM degradation of articular components in RA. PMID- 11213362 TI - Inhibition of inducible nitric oxide synthase and cyclooxygenase-2 expression by flavonoids in macrophage J774A.1. AB - The present study focuses on the effect of various naturally occurring flavonoids (apigenin, galangin, morin, naringenin, quercetin, and silymarin) on nitric oxide (NO) and prostaglandin E2 (PGE2) production induced by lipopolysaccharide (LPS) in the macrophage cell line J774A.1. Moreover, we evaluated flavonoid modulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) enzyme expression by western blot analysis. Apigenin and quercetin (0.5-50 microM) were the most potent inhibitors of NO production and this effect was concentration dependent and significant at 5 and 50 microM. These data were consistent with the modulation of iNOS enzyme expression. A similar pattern was observed considering the inhibitory effect of flavonoids on LPS-induced PGE2 release and COX-2 expression. Quercetin, galangin, apigenin, and naringenin markedly decreased PGE2 release and COX-2 expression in a concentration-dependent manner. This study suggests that inhibition of iNOS and COX-2 expression by flavonoids may be one of the mechanisms responsible for their anti-inflammatory effects. PMID- 11213363 TI - Uptake by vascular smooth muscle cells plays an important role in targeting of lipid microspheres incorporating prostaglandin E1 into a thickened intima. AB - A study was done to determine how lipid microspheres (LM) containing prostaglandin E1 (lipo PGE1) accumulate in injured arterial tissue. After administration of lipo PGE1 labeled with a fluorescence probe, 1,1'-dioctadecyl 3, 3, 3',3'-tetramethyl-indocarbocyanine perchlorate (DiI-lipo PGE1) to rats 14 of days after balloon injury of the carotid artery, localization into the injured site was examined using a fluorescence confocal laser scanning microscope (CLSM). In contrast with the normal carotid artery, DiI-lipo PGE1 accumulated remarkably in neointima of the injured site which was occupied mainly by the migration of the proliferating and quiescent vascular smooth muscle cells (SMC). In vitro cellular uptake of DiI-lipo PGE1 was semi-quantitatively measured using CLSM, regarding differentiated and proliferative phenotypes of human vascular SMC, compared with the human endothelial cells (EC) and mouse fibroblasts. The differentiated SMC incorporated DiI-lipo PGE1 to equal or a higher level of the proliferative phenotype, and was significantly higher than EC and fibroblasts. The uptake of DiI-lipo PGE1 by both SMC and EC was inhibited at 4 degrees C, by dansylcadaverine and excessive LM, but was unaffected by cytochalasin B. These results suggest that the uptake of DiI-lipo PGE1 by SMC plays an important role in localization of DiI-lipo PGE1 at the injured site, and that the uptake seems to be a receptor mediated endocytosis. PMID- 11213364 TI - Effects of melatonin, morphine and diazepam on formalin-induced nociception in mice. AB - The possible analgesic effect of melatonin was investigated in young male ICR mice. The formalin test which elicits typically 2 phases of pain response, the acute (first) phase and tonic (second) phase, was used. The test was performed in the late light period when the mice have been reported to be more sensitive to pain. Compared to control mice, no significant difference in nociceptive response was observed when melatonin was injected intraperitoneally at doses of 0.1, 5, and 20, mg/kg body weight. The combined effects of melatonin with diazepam and/or morphine, were also investigated. Melatonin, injected at 20 mg/kg 15 min before formalin test, significantly increased the antinociceptive response of diazepam (1 mg/kg) or morphine (5 mg/kg) in the second phase. In addition, when melatonin was given at 20 mg/kg together with diazepam and morphine, antinociceptive responses in both the first and second phase were increased. These data indicate the synergistic analgesia effect of melatonin with morphine and diazepam and suggest the possible involvement of melatonin as an adjunct medicine for pain patients. PMID- 11213365 TI - Endothelium-independent vasorelaxation by leonurine, a plant alkaloid purified from Chinese motherwort. AB - Leonurine, a plant alkaloid present in Chinese motherwort, induced concentration- dependent and endothelium-independent relaxation of phenylephrine (PE)- pretreated rat aortic arterial rings. The IC50 values for leonurine were 86.4+/ 10.4 and 85.9+/-17.2 microM in the presence and absence of endothelium respectively. It inhibited the responses of aortic smooth muscle to PE in Ca2+ free medium containing 100 microM EGTA, suggesting a possible action on the release of intracellular Ca2+. Leonurine is not a specific alpha-adrenoceptor blocker, since it also caused a concentration-dependent inhibition of vascular contractile responses to KCl with an IC50 value of 96.4+/-13.4 microM, suggesting that leonurine also blocks the L-type Ca2+-channel. In addition, leonurine relaxed the aortic contraction induced by prostaglandin F2alpha (PGF2alpha). These inhibitory effects of leonurine were reversible and did not affect the resting tension. In conclusion, these findings suggest that leonurine is an effective inhibitor of vascular smooth tone, probably acting by inhibiting the Ca2+ influx and the release of intracellular Ca2+. PMID- 11213366 TI - Angelica sinensis modulates migration and proliferation of gastric epithelial cells. AB - A crude extract from Angelica sinensis (ASCE), which mainly consists of polysaccharides, prevents ethanol- or indomethacin-induced gastric mucosal damage and promotes ulcer healing. The aim of this study was to test the hypothesis that ASCE has a direct stimulating effect on gastric epithelial cells for wound healing. We found that ASCE significantly promoted the migration of epithelial cells over an artificial wound on the surface of an RGM-1 monolayer. The extract also stimulated DNA synthesis in a dose-dependent manner and concomitantly increased EGF mRNA expression. Co-incubation of ASCE with anti-EGF antibody reduced the speed of migration and the DNA synthesis, which however were still higher than the control without ASCE. These results strongly suggest that ASCE has a direct wound healing effect on gastric mucosa, and this is acting partially through an EGF-mediated pathway. PMID- 11213367 TI - Biological properties of Phe(o)-opioid peptide analogues. AB - Biological properties of new analogues, which represent Phe(o)-propeptides of a variety of opioid peptides, are described. All Phe(o)-opioid analogues expressed both receptor binding affinities and in vitro biological activities at least at the level of the primary opioid peptides. Surprisingly, some of the propeptides expressed slightly higher activity than the primary opioid peptides. Nevertheless, no significant shift in receptor selectivity was observed, which indicate that these Phe(o)-analogues undoubtedly are propeptides. The possible role of membrane proteolytic enzymes associated with opioid receptors in transformation of propeptides is discussed. PMID- 11213368 TI - Marketplace. With workers' compensation outlays set to rise there's renewed interest in how to contain costs. PMID- 11213369 TI - Perspectives. Burgeoning technology will strain Medicare more than previously admitted, says panel. PMID- 11213370 TI - Current practice in assessment and treatment of bronchial asthma in young males in Italy. AB - The aim of the study was to evaluate, in a sample of young asthmatics in Italy, the current practice in assessment and treatment of asthma after the publication of guidelines. Young soldiers who declared bronchial asthma at the beginning of the compulsory military service were evaluated. One-hundred and thirty-eight subjects with confirmed asthma were selected. Sixty-seven subjects (48.5%) had had at last one spirometry, and only one subject had underwent peak flow monitoring at home; most of the subjects (96.8%) had had prick tests. More of the 50% of the subjects with bronchial obstruction or with severe bronchial hyperresponsiveness, with clinical moderate or severe asthma, had used only bronchodilators or no therapy at all in the preceding year. In this sample of young asthmatics, the lung function tests were still underutilized for the diagnosis and follow-up of bronchial asthma; moreover, the inhaled anti inflammatory drugs were still underutilized. PMID- 11213371 TI - Perception of methacholine-induced airway obstruction in asthmatics. AB - The main objective of this study was to examine the perception of the first symptom during methacholine bronchoconstriction as soon as it occurred, and in the second instance to quantify the intensity of the breathlessness by means of the Borg Scale performed at the end of challenge so to not determine any difficulties for identification of the first symptom. A methacholine challenge test was carried out in 139 symptom-free asthmatics with a normal pulmonary function. When the first symptom was reported by the subject, the forced expiratory volume in one second (FEV1) was measured immediately. FEV1 was expressed as a percentage of the best personal value (FEV1%BPV). The intensity of the breathlessness was rated using a modified Borg Scale at the end of the challenge test so as not to confuse the patient. Seven subjects felt nothing during challenge. The first symptoms varied: constriction behind the breastbone (49%), inspiratory shortness (16.5%), coughing (10%), wheezing, throat constriction, general chest tightness, pain behind the sternum, and a sensation of rheum behind the sternum. FEV1%BPV at the first symptom was 80.5 +/- 10 (range 41-99). No symptom was perceived by 42% of the subjects within the 80-100 range of FEV1%BPV. FEV1%BPV at the first symptom was related to the log of the provocative dose causing a 20% fall in FEV1 (r = 0.2, p < 0.05). An inverse correlation between Borg Score and final FEV1%BPV (r = -0.25, p < 0.01) was found at the end of challenge. A subgroup of 39 subjects with similar final FEV1%BPV values (68-72) showed a correlation between the Borg Score at end of challenge and FEV1%BPV at the first symptom (r = 0.59, p < 0.001). The first symptom of the methacholine-induced bronchoconstriction varies in asthmatics and may be atypical, the bronchoconstriction level at which it is felt also varies among individuals, highly methacholine-responsive subjects perceive the bronchoconstriction later, while late perceivers of the first symptom show less intense breathlessness at the end of challenge. The measurement of the patient's ability to perceive asthmatic symptoms during the methacholine challenge test could be used to single out poor perceivers. PMID- 11213372 TI - Accuracy of indirect estimation of oxyhaemoglobin saturation in patients with respiratory failure. AB - The indirect estimate of oxyhaemoglobin saturation (Sa,O2) is largely used in the management of patients with respiratory failure. The aim of this study was to evaluate the accuracy of the Sa,O2 values calculated by using both the Siggaard Andersen (SA) and the Severinghaus (SE) equation, in comparison with the real Sa,O2 values measured by a co-oximeter. A total of 558 arterial blood samples were analysed. On average, only a slight overestimation was found for Sa,O2 estimated by the SA (2.35 +/- 5.75%) and the SE (2.37 +/- 5.65%) equations in comparison with the real values. However, a difference higher than 5% between estimated and real Sa,O2 values was demonstrated in more than 20% of the blood samples evaluated. This difference was higher than 10% in 9% of the samples, with similar results obtained with the two equations. The discrepancy between real and estimated values, probably due, at least in part, to errors in measurement of arterial oxygen tension (Pa,O2) and pH, was maximally evident for Sa,O2 values lower than 70%. An indirect estimate of Sa,O2 is not homogeneously accurate, and the clinical consequence of this finding might be especially dangerous in monitoring patients with severe respiratory failure. PMID- 11213373 TI - Bronchial atresia with mucocele in an adolescent girl: an uncommon cause of lobar emphysema. AB - Congenital bronchial atresia (CBA) is a congenital anomaly but is seldom diagnosed in children. They are usually asymptomatic and are found during screening chest radiographs in young adults. The characteristic chest radiographs of CBA consist of a hyperlucent lung, central branching but contrast non enhancing mass and air-fluid lesion. Most of the cases reported in the past were managed surgically. The present study reported an 11-yr-old presenting with chest pains, exercise intolerance, and refractory wheezing. It is of utmost importance to consider the possibility of CBA in children with lobar emphysema in order to achieve early diagnosis and avoid unnecessary exploratory surgery. PMID- 11213374 TI - Sarcoidosis in a patient with 5q-myelodysplasia. A possible pathogenetic link between the two diseases. AB - This study describes the occurrence of sarcoidosis with lung and skin involvements in a 56-yr-old woman who suffered from 5q-myelodysplastic syndrome since the age of 50. The 5q-myelodysplastic syndrome is marked by deletion of the long arm of chromosome 5, which carries the genes coding for T-helper cell 2 cytokines, such as interleukins-3, -4 and -5, and granulocyte-macrophage colony stimulating factor. Although the aetiology of sarcoidosis remains unclear, sarcoid granulomatous inflammation is marked by predominant expression of T helper cell 1 cytokines, with reduced expression of T-helper cell 2 cytokines. The authors suggest that 5q-abnormality may have predisposed to sarcoidosis through an imbalance in the cytokine network, caused by the deletion of genes coding for T-helper cell 2 cytokines. PMID- 11213375 TI - Mycobacterium tuberculosis and HIV co-infection in the lung: synergic immune dysregulation leading to disease progression. AB - There is evidence that Mycobacterium tuberculosis (Mtb) impacts on human immunodeficiency virus (HIV) infection and that HIV promotes mycobacterial diseases. Epidemiological and clinical studies demonstrate the detrimental effect of tuberculosis (TB) on the progression of HIV infection, that is an increased risk of death among Mtb-HIV co-infected patients. Pulmonary TB may occur very early during HIV infection, whereas extrapulmonary or atypical manifestations are associated with more profound immunodeficiency, showing features like mycobacteraemia and multi-drug resistance, much more severe than in immunocompetent hosts. During the last decade, many efforts have been focused on the immunological aspects of Mtb-HIV co-infection. The host protective response to TB is mediated by cell immunity, which, mainly supported by interleukin (IL) 12 and interferon (IFN)-gamma production, leads to granuloma formation. Perturbations in the cytokine expression, that is a reduced type-1-like response, have been suggested in HIV-infected patients to contribute to their susceptibility to TB. Indeed, an impaired balance between pro-inflammatory and anti-inflammatory cytokines and apoptosis-induced depletion of immune effector cells account for the dissemination of both the pathogens and for a poor granulomatous reaction in Mtb-HIV co-infected patients. However, the recently elucidated role of chemokines and their receptors in immune regulation opens new questions on the pathogenesis of Mtb-HIV co-infection. PMID- 11213376 TI - New therapeutic approach to persistent asthma. AB - The goal of asthma treatment has moved from achieving symptom relief alone to overall disease control. The latest guidelines propose that first-line treatment of mild persistent asthma requires the introduction of anti-inflammatory agents, preferably inhaled corticosteroids at low dose. In patients in whom control of disease is not achieved with this treatment, it was demonstrated that addition of a long-acting beta 2-agonist is more effective than increasing the dose of inhaled corticosteroid. Addition of a long-acting beta 2-agonist to an inhaled corticosteroid not only improves symptoms and lung function but also reduces the risk of asthma exacerbations, suggesting complementary therapeutic activity. Therefore, use of long-acting bronchodilators with inhaled corticosteroids is a prerequisite for optimal management of the disease. For this reason, the logical development in asthma management would be a combination of these two classes of drug in a single inhaled formulation. Fixed combinations of the long-acting beta 2-agonist salmeterol and the inhaled corticosteroid fluticasone propionate were launched recently. Results from recent clinical trials have demonstrated that the combination of salmeterol and fluticasone propionate improves control of asthma in the majority of patients with moderate-to-severe asthma and enhances compliance by virtue of both drugs being in the one inhaler. The possibility to treat asthma of differing severity is provided by the flexibility to choose between three different doses of fluticasone propionate in the fixed combination devices. Another obvious advantage of the combination is cost savings, as the fixed combination inhaler is cheaper than giving the two drugs separately. The introduction of combination preparations is an important step forward in asthma management, which is expected to be a popular choice with both patients and physicians. PMID- 11213377 TI - What is liquid breathing and ventilation? AB - Liquid ventilation is a rapidly growing ventilation technique. In spite of the large number of scientific and technical papers on the argument, the general concepts, particularly useful for the non-specialist physician, are not easy to acquire. The scope of this simple review is to explain the present general aspects and uses of liquid ventilation, analysing their chronological development. PMID- 11213378 TI - Contribution of upper airway reflexes to apnoea reversal, arousal, and resuscitation. AB - Cardiorespiratory decompensation or even death may result from dysfunction of upper airway reflexes during sleep. This could manifest, for example, as a lack of pharyngeal dilation in obstructive sleep apnoea or failure of autoresuscitation by gasping in sudden infant death syndrome. Data obtained from experiments in anaesthetized cats suggest several clinicophysiological applications for upper airway reflexes possessing important pathogenetic and therapeutic potentials. Such reflex effects include: 1. Pharyngeal dilation as additional treatment in obstructive sleep apnoea. 2. Bronchodilation after deep nasal breathing in asthmatic attacks. 3. Oesophageal sphincter relaxation alleviating gastro-oesophageal reflux. 4. Provocation of sniff- and gasp-like aspiration for reversal of central apnoea. 5. Arousal from sleep increasing the general reactivity. 6. Increase in muscle tone underlying behavioural defence reactions. 7. Increase in sympathetic activity contributing to powerful cardiopulmonary-cerebral resuscitation. 8. Adrenergic reaction mediated by catecholamine secretion. PMID- 11213379 TI - Sleep apnoea syndrome: the health economics point of view. AB - This review analyses the available literature on the economic aspects of obstructive sleep apnoea, including the indirect medical costs, the indirect nonmedical costs, the direct costs of diagnosing and treating the disease, and the utilities as perceived by patients. The philosophical context of health economics is also considered. The literature available on the economic aspects of obstructive sleep apnoea is scarce, and frequently incomplete, so that only tentative conclusions can be reached. Obstructive sleep apnoea seems to lead to measurable (about two-fold) increases in indirect medical costs. Moreover, this excess cost seems to be reduced in the first years following the institution of treatment with nasal continuous positive airway pressure (nCPAP). There are also indirect nonmedical costs linked to the disease, for example traffic, domestic and workplace accidents. The exact extent of these costs is, however, impossible to ascertion from the available literature. Cost/utility analysis has shown full night polysomnography to be the diagnostic approach with the higher cost/utility ratio, because diagnostic errors (greater with other approaches) carry a disproportionate weight. The cost of treating the disease has not been thoroughly assessed but appears as quite reasonable, and certainly not excessive. Finally, one study has shown in patients with severe sleep apnoea that treatment with nCPAP has a favourable effect when measured as quality adjusted life years. It is concluded that obstructive sleep apnoea leads to an excess in health-related expenditure, that treatment with nasal continuous positive airway pressure reduces this excess cost and thus makes sense in economic terms, and that patients believe nasal continuous positive airway pressure treatment to be worth considering for economic reasons. It is further concluded that medical decisions should be guided by medical (not economic) considerations, even if it is acknowledged that, for the time being, economic analysis is necessary to to convince health managers that obstructive sleep apnoea is also worth considering from the economic point of view. PMID- 11213380 TI - Potential usefulness of inhibiting neural mechanisms in asthma. AB - The airway innervation consists of a cholinergic system, an adrenergic system, and a non-adrenergic, non-cholinergic (NANC) system. Anticholinergic drugs have long since been used in the treatment of asthma and chronic obstructive pulmonary disease (COPD). The new anticholinergic drug, tiotropium bromide, causes long lasting bronchodilatation (> or = 24 h) in patients with COPD. The sensory airway neuropeptides, substance P (SP) and neurokinin A (NKA), are potent contractors of smooth muscle, vasodilators and have important proinflammatory effects. Their airway effects are mediated by tachykinin NK1 and NK2 receptors. Antagonists for these receptors are currently being developed as a possible treatment of obstructive airway diseases. PMID- 11213381 TI - Acute exacerbations in chronic obstructive pulmonary disease (COPD)--microbial patterns and risk factors. AB - Around 25% of patients with stable chronic obstructive pulmonary disease (COPD) show some evidence of tracheobronchial colonization. It is, however, probable that the vast majority of patients become colonized at some time during the course of the disease. A variety of factors including current smoking and viral infections predispose to bacterial colonization and subsequently acute exacerbations. In fact, infectious aetiologies account for around 50-75% of acute COPD exacerbations. Bacterial pathogens are present in around 50% of patients, Haemophilus influenzae and Streptococcus pneumoniae being the most frequently encountered pathogens. Pseudomonas aeruginosa and probably also Gram-negative enteric bacilli are more frequently found in patients with more severe airflow limitation. Viral infections are present in around 10-20%, with Influenzavirus representing the most frequent viral pathogen. Only recently, evidence for infection by Chlamydia pneumoniae has been found in 5-20% of patients. Predictors of distinct aetiologies have only infrequently been studied so far. Thus, it currently remains difficult to make adequate predictions on clinical grounds in the individual patient. Nevertheless, we would advocate to tentatively stratify the initial antimicrobial treatment according to the severity of the acute exacerbation episode and the presence of individual risk factors. The validation of such an approach may result in significant progress in our understanding of the role of infection and infectious agents in different subgroups of patients with acute exacerbations. PMID- 11213382 TI - Complementary investigations in bronchiectasis in children. AB - The different modalities suitable for image-guided diagnosis of bronchiectasis in children are described. Plain chest radiography is still the most important imaging method of respiratory disease in children, but when it comes to ascertaining the diagnosis of bronchiectasis, high-resolution computed tomography (CT) is currently the method of choice. Ultrafast computed tomography and multislice computed tomography have increased the value of computed tomography as a diagnostic tool by reducing the need for sedation or anaesthesia. Bronchography is as a rule no longer necessary to perform on this indication alone. If modern, high-quality computed tomography is not readily available, however, bronchography may still be necessary preoperatively. PMID- 11213383 TI - Tidal breathing at all ages. AB - Measurement of lung function during tidal breathing may be performed regardless of the age and respiratory state of the patient. This is particularly advantageous in young children in whom forced respiratory manoeuvres cannot be performed, but has also been found useful in adults with various chest diseases. The most frequently reported tidal breathing parameters are mathematical expressions of the shape of the tidal flow/volume (TFV) loop or tidal flow/time traces, as the ratio of the time or volume taken to reach peak expiratory flow to total expiratory time or volume (tPTEF/tE or VPTEF/VE, respectively). However, new parameters have been suggested, focusing on the shape of the latter portion of the curve. Standardization of measurements is important, and more studies are required to settle some of the issues regarding, for instance, how many curves to evaluate, which parameter to report and how to perform challenge or reversibility tests. Intra-individual variation should be kept to a minimum, preferably performing measurements under the same conditions on each occasion. The issue of whether to sedate is a subject of debate. However, with experience, reproducible TFV measurements may be obtained in most subjects in the awake state, regardless of age, provided the setting is friendly and calm. TFV measurements have provided important information in research as well as clinical settings. Reduced tPTEF/tE has been demonstrated in newborn term and premature babies born to smoking mothers, and is a risk factor for recurrent wheeze within the first 3 yrs of life. Also, tPTEF/tE is clearly reduced in subjects with acute bronchial obstruction (BO) (such as occur in bronchiolitis), but also in asymptomatic children with BO for other reasons, such as asthma. Significant response to histamine and methacholine as well as to bronchodilator has been demonstrated in preschool children, adults and animals (horses, dogs and cats). The present paper discusses various practical issues concerning and possible uses of tidal flow/volume measurements. In conclusion, tidal flow/volume measurements may be important supplementary tools in the investigation of respiratory disease in both research and clinical work in subjects who for any reason cannot cooperate with more conventional lung function measurements. PMID- 11213384 TI - [Quality control in hemodialysis: quality assurance process]. AB - The development of a quality assurance step in hemodialysis replies to the needs of the accreditation process defined in the hospital reform and the related ordinances edited in April 1996. This global concept is set to continuously improve the quality care and the outcomes of the hemodialysis patients. The thought behind this work has two objectives: provide guidelines to guaranty quality and adequacy of hemodialysis treatment schedule in ESRD patients; anticipate standard rules edited by regulatory authorities for quality indices and control process in hemodialysis. The final aim of this work is also to demonstrate that the quality assurance process in hemodialysis should not be perceived as an extra administrative burden but rather as a new opportunity to establish good medical practice rules in the peculiar domain of renal replacement therapy. PMID- 11213385 TI - [Renal osteodystrophy (3); its treatment in dialysis patients]. AB - The prevalence and the clinical gravity of the various histopathological varieties of renal osteodystrophy in dialysis patients depends on the severity of both the aluminium intoxication and that of hyperparathyroidism. The prevalence of bone pains, fractures and hypercalcemias are the highest in adynamic bone diseases (ABD) with severe aluminium intoxication, then in osteitis fibrosa and mixed osteopathy, in the ABD with moderate aluminium intoxication and rare in the mild lesion in spite of similar moderate aluminium intoxication. In the absence of aluminium intoxication, hypercalcemia and hyperphosphatemia prevalence is higher only when intact PTH is more that 4 times the upper limit of normal. When PTH is between 1 and 2 folds the ULN this prevalence is null and bone mineral density is the highest. 2. The low turnover aluminic bone diseases (osteomalacic or adynamic) will be cured by long term deferoxamine treatment. The hazards of such treatment justify the performance of a bone biopsy to ensure the diagnosis. Their prevention relies on adequate treatment of tapwater and definitive exclusion of long term administration of aluminum phosphate binders. 3. Non aluminic osteomalacia will be treated according to the same guidelines given for the uremic patients before dialysis. 4. Non aluminic adynamic bone disease will be cured by means aiming at stimulating PTH secretion as discontinuing 1 alpha hydroxylated vitamin D derivatives, and, if there is no hyperphosphatemia by discontinuation of calcium supplement. In case of hyperphosphatemia in dialysis patients CaCO3 doses have to be nevertheless increased after the dialysate calcium concentration (DCa) has been decreased in order to induce a negative perdialytic calcium balance for PTH secretion stimulation. In the near future substitution of CaCO3 by non calcemic non aluminic phosphate binders will suffice. 5. Osteitis fibrosa due to hyperparathyroidism will be treated first by securing an optimal vitamin D repletion (bringing plasma 25OH vitamin D around 30 and 60 ng/ml or 75-150 nmol/l) and by correcting hypocalcemia and hyperphosphatemia by CaCO3 at high doses (3-12 g/day) taken with the meals. In case of hypercalcemia dialysate calcium concentration will be decreased to correct it or, in a near future, CaCO3 will be decreased to 3 g/day and hyperphosphatemia will be controlled by non calcemic, non aluminic phosphate binders. When hyperphosphatemia is controlled whereas plasma calcium is normal or low, 1 alpha hydroxylated vitamin D derivatives can be administered. 6. Instrumental parathyroidectomy should be considered when plasma levels of intact PTH remain above 7 folds the upper limit of normal whereas hyperphosphatemia persists and hypercalcemia occurs in order to prevent thining of the corticals and subsequent fracture risk. In case of previous exposition to aluminum, a deferoxamine test and/or a bone biopsy will be performed to decide a long term DFO treatment before the parathyroidectomy in order to prevent the transformation of a mixed osteopathy into an aluminic adynamic bone disease. 7. The difficulty of hyperparathyroidism control in dialysis patients is due to poor compliance to phosphate binders and to irreversible parathyroid hyperplasia with occured before the dialysis stage. This stress the primary importance if its early prevention without iatrogenia by first CaCO3 and vitamin D repletion, as soon as the creatinine clearance decreases below 60 ml/min/1.73 m2. PMID- 11213386 TI - [Selective inhibitors of type 2 cyclooxygenase: less renal effects than the classical non-steroidal anti-inflammatory agents]. AB - Prostaglandins play an important role in the regulation of renal hemodynamics and sodium excretion. Thus, the administration of non-steroidal anti-inflammatory drugs (NSAIDs) induces a renal vasoconstriction and sodium and potassium retention. In some high risk patients, this may lead to acute renal failure. The anti-inflammatory and renal effects of conventional NSAIDs are mediated by the non-selective inhibition of two cyclo-oxygenases, COX-1 and COX-2. Recently, highly selective COX-2 inhibitors have been developed such as celecoxib (Celebrex) and rofecoxib (Vioxx). These drugs were designed to preserve the analgesic and anti-inflammatory properties of NSAIDs while reducing their gastro intestinal and renal side effects. Selective COX-2 inhibitors have indeed less gastro-intestinal side-effects. However, their renal profile is comparable to that of non-selective inhibitors as they induce a decrease in glomerular filtration rate and a sodium and potassium retention. Thus, despite the good gastro-intestinal safety profile of selective COX-2, one should be careful with the use of these agents in high risk patients as they may induce similar renal complications as non-selective NSAIDs. PMID- 11213387 TI - [Value of an end-stage renal failure registry. Experience of the Champagne Ardenne region]. AB - Since 1992, a registry gathering all the patients with end-stage renal failure is established in Champagne-Ardenne. It is based upon demographic data and allocation of dialysis treatment. It is supported by regional nephrologists. It is exhaustive and has been validated by the regional health administration. It is the only data base considered for the regional scheme of sanitary organization. In 1999 the incidence of terminal renal failure was 119 pmp and, at 1 January 2000, prevalence of uremic patients treated with supportive therapy, except transplantation, was 426 pmp. Our registry may be used as a regional registry awaiting to participate into built the national program project REIN (Renal Epidemiology and Information Network) and to help better health care policy and costs containment. PMID- 11213389 TI - [The "Ana Rosa syndrome" in scientific literature]. PMID- 11213388 TI - [Diffuse colitis associated with mycophenolate mofetil treatment: apropos of 1 case]. AB - Mycophenolate mofetil (MMF) or Cellcept is a potent immunosuppressor that inhibits purin synthesis used to prevent human allograft rejection. The most important secondary effects include haematological and intestinal disorders. Among them, diarrhea is the most common. It is dose-dependant and appears commonly during the first 2 months of treatment. Its physiopathology remains unclear. We reported a case of colitis, 6 months after a kidney transplantation. The patient was treated since day 2 with 2 grams per day of MMF. Morphological analysis showed a diffuse colitis from the coecum to the rectum. Histological samples confirmed a colitis with atrophic crypts but with mucosal secretions and some cryptic abscesses. No granuloma or CMV inclusion was founded. Histochemical immunostaining for CMV was negative. Finally, symptoms regressed within 5 days after tapering down MMF dose in association with metronidazole treatment. The role of MMF in inducing colitis is discussed. PMID- 11213390 TI - [Recovery of circumcision as medical practice in Miguel Servet's literature]. PMID- 11213391 TI - [Analysis of 83 urethroplasties for urethral stenosis]. AB - OBJECTIVE: To determine the appropriate technique for each case of urethral stricture, according to its length, depth, localization, etiology and age of the patient. METHODS: 83 urethroplasties for urethral stricture performed from 1992 1998 were reviewed. The strictures involved different levels of the urethra. The techniques utilized were analyzed (substitution urethroplasty with pedicle skin graft and free grafts using buccal mucosa and extragenital skin, excision and anastomotic repair, regeneration techniques with internal urethrotomy and placement of intraluminal prosthesis, and two-stage repair procedures). RESULTS: The overall functional results were good in 93% of the cases (78 good, 5 poor), but the morphological results demonstrated by the radiological findings were not as good in 24% of the cases, which corresponded to those that had received preputial pedicle grafts and buccal mucosa free grafts. CONCLUSION: Using the appropriate urethroplasty technique is essential to achieve good functional results. The substitution techniques require well-vascularized grafts and/or recipient sites. The foregoing must be taken into account in the selection of the appropriate graft and deciding on the stricture length and localization. PMID- 11213392 TI - [Immunotherapy in superficial bladder carcinoma]. AB - OBJECTIVE: To review the current status of superficial bladder cancer treatment with several immune response modifiers. METHODS: A review of the advances in the treatment of superficial bladder cancer with BCG, interferon, interleukin-2, bropirimine and keyhole-limpet hemocyanin was performed. RESULTS: Treatment with BCG has been demonstrated to be superior to intravesical chemotherapy and other immune response modifiers in the trials reviewed. BCG therapy, however, carries a higher toxicity. Several trials have demonstrated that in low and medium risk patients, it is better to administer low BCG doses to reduce the toxicity. Furthermore, the trials confirm the utility of maintenance schedules with BCG. CONCLUSION: The Calmette-Guerin Bacillus is the most effective adjuvant treatment in superficial bladder cancer, especially in the high risk patients. The other immune response modifiers are an alternative to this treatment. PMID- 11213394 TI - [Characteristics of prostatic cancer undetected in the first assessment of a screening program. Quality control]. AB - OBJECTIVE: To study the results of the second round in the subjects with negative tests in the first round of a prostate cancer screening program and to analyze the characteristics of the tumors that were not detected in the first round. METHODS: Of 5188 males evaluated in a prostate cancer screening program, 976 with negative tests in the first round (804 with PSA < or = 4 ng/ml; 172 with PSA > 4 ng/ml and a negative biopsy) accepted to undergo subsequent tests. During the second round, 163 biopsies were indicated. The biopsy results and the characteristics of the tumors detected were analyzed. RESULTS: The biopsy yield was higher (but not significantly) in the first round (80 cancers/481 biopsies; 16.6%) than in the second round (13 cancers/115 biopsies; 11.3%). Of the 163 biopsies indicated in the second round, 115 were performed and 13 cancers were detected (10 of these patients had a high PSA in the first round). The univariate analysis showed no differences for age, PSA, PSA density, prostate volume, transrectal US findings, or Gleason score in the cases diagnosed in the first round and those detected in the second round. However, there was a higher proportion of tumors with abnormal DRE in the cancers detected in the first round than in the second round, (31.3% vs 7.7%, respectively; p = 0.02). There was a higher proportion of tumors clinically detected in the second round than in the first round (100% vs 75%, respectively; p = 0.043). The multivariate analysis only showed differences for the DRE findings (p = 0.045). CONCLUSION: A significant number of tumors are undetected in prostate cancer screening programs. Although the biopsy yield may be slightly lower in subsequent rounds, there is a strong trend of detecting more localized tumors (and therefore potentially curable). We have found no correlation between a greater prostate volume and tumors that were undetected in the first round. PMID- 11213395 TI - [Laparoscopic approach through optic trocars]. AB - OBJECTIVE: Laparoscopy has not reached the same levels of development in Urology as it has in other surgical specialties. Consequently, the average urologist is not sufficiently accustomed to using laparoscopic trocars, a difficulty which becomes even more noteworthy since treatment is occasionally preferably by the extraperitoneal approach (preperitoneoscopy and retroperitoneoscopy). Our experience with different visualizing trocars is presented. METHODS: We reviewed our experience with different visualizing trocars. The advantages and inconveniences of each type, utilized in different approaches, are discussed. RESULTS: Active visualizing trocars are preferred because they are safe and permit pre and retroperitoneal blunt dissection without difficulty. However, cost is the major disadvantage of these instruments because they are not reusable. CONCLUSION: Lately, we are more inclined to utilize the reusable visualizing trocars with the helicoidal cannula, which are very safe for the transperitoneal and perhaps slightly less for the extraperitoneal approach. These instruments cause less injury when they go through the abdominal wall and, furthermore, they cost less. PMID- 11213393 TI - [Studer-type orthotopic urinary bladder: our experience]. AB - OBJECTIVE: To analyze the outcome, complications and functional results in patients undergoing bladder substitution with the Studer continent urinary pouch. METHODS: The clinical records of 6 male patients who underwent radical cystectomy for invasive bladder cancer and bladder substitution with the Studer reservoir at our hospital from January 1996 to February 2000 were reviewed. Patient mean age was 54.2 years and mean follow-up was 14 months. Follow-up evaluation included abdominopelvic CT, chest x-ray, urinalysis, blood biochemistry, venous gasometry and ultrasonography with evaluation of postvoid residual urine. RESULTS: Transitional cell carcinoma was found to be the most frequent histopathological type. Distribution by grade and pathological stage showed they were all high grade infiltrating tumors localized to the bladder. Four patients are free of disease, one died from metastatic disease and one patient with tumor progression and multiple lung metastases at two months' follow-up is currently on chemotherapy. The mean operating time was significantly longer for this procedure than for the non-continent Bricker urinary diversion (mean 7.2 hours vs 3.5 hours, respectively). The immediate postoperative complications were: ileus (> 7 days) in two patients, diarrhea (> 3 days) in two, occlusive ileus due to fecaloma in one, metabolic acidosis in one, wound seroma in one, and wound infection in two patients. The early and late postoperative complications were: incontinence for up to one month after removing the urethral catheter in three patients (two of these patients are still incontinent at two months' follow-up), wound infection in two and impotence in 6 patients. CONCLUSION: Reservoir function in the medium-term is good; spontaneous urethral micturition and continence are maintained. To achieve good results, patients should be followed carefully and should be given detailed information about postoperative care and management. PMID- 11213396 TI - [Diagnosis and therapeutic options for prolonged erection and priapism: up-date review]. AB - OBJECTIVE: To review the pathophysiology, diagnostic methods and treatments of priapism, with special reference to alternative treatment options. METHODS: The different surgical options are presented and discussed, with special emphasis on the oral drugs and intracavernous therapy for priapism. The advantages and inconveniences of the different agents and surgical techniques are discussed. The publications in MEDLINE 1980-2000, our experience and the results of our studies previously reported in the literature were reviewed. RESULTS/CONCLUSIONS: Complete detumescence and recovery of normal arterial blood flow can be achieved in a majority of the cases by systematic and standardized management. Sedatives, alpha-adrenergic agents or oral ketamine hydrochlorate can be utilized. However, due to the importance of the time factor, intracavernosal therapy should be the priority for persistent erection, using alpha-adrenergic agonists or other alternatives, such as methylene blue, which do not have the well-recognized risks of the conventional agents. The etiology of the priapism should be clearly established by metabolic and hemodynamic studies, since treatment will be based on the underlying disorder. In veno-occlusive low flow priapism, surgical shunting should be performed if aspiration of intracavernosal blood and other treatments are not successful. Arterial embolization and surgical ligation should be performed for high flow persistent priapism. PMID- 11213397 TI - [Low-flow priapism associated with systemic lupus erythematosus and nephrotic syndrome]. AB - OBJECTIVE: To present a case of priapism associated with systemic lupus erythematosus and nephrotic syndrome. METHODS: A 29-year-old male patient with a history of multiple pathologies consulted at the emergency services with painful priapism of 12 hours' duration. The intracavernosal aspirated blood had a venous appearance. Among the risk factors analyzed, systemic lupus erythematosus and nephrotic syndrome are recognized to cause hypercoagulability, a condition that can lead to low flow priapism. RESULTS: There was no response to lavage aspiration or intracorporeal administration of an alpha-adrenergic agonist. The high surgical risk of the patient advised against surgery. The priapism gradually diminished until complete remission on the sixth day. The patient has remained without spontaneous erection. CONCLUSION: Systemic lupus erythematosus and nephrotic syndrome can cause low flow priapism. The best treatment is by prevention with adequate antithrombotic prophylaxis. PMID- 11213398 TI - [Isolated primary hyperaldosteronism caused by adrenocortical carcinoma]. AB - OBJECTIVE: To report a case of adrenocortical carcinoma and primary aldosteronism as the sole endocrine manifestation. METHODS/RESULTS: A 39-year-old male with adrenocortical carcinoma and primary aldosteronism is presented. Following complete hormonal and radiological evaluation, right adrenalectomy and nephrectomy were performed (pT2pN0M0, stage II). Blood pressure, serum potassium and aldosterone levels returned to normal. The patient received adjuvant therapy with carboplatin and etoposide. After 15 months' disease-free interval, lung metastasis was diagnosed, without evidence of local recurrence until 5 months later, when hypertension and primary hyperaldosteronism reappeared. There were no other endocrine disorders. Treatment with spironolactone, 5-FU and adriamycin was instituted with no tumor response and the patient died 3 years later from complications of endobronchial metastasis. CONCLUSION: Adrenocortical carcinoma with isolated primary hyperaldosteronism is uncommon and consequently there is no wide experience in regard to its diagnosis and treatment. Although randomized studies are not available, adjuvant therapy using other agents instead of mitotane (o,p-DDD), such as the combination of cisplatin and etoposide (VP-16), seems reasonable in the locally advanced stages. Mitotane may be useful when hypercortisolism is present, but its efficacy as an antitumor agent has been controversial. PMID- 11213399 TI - [Leiomyoma of the bladder]. AB - OBJECTIVE: To report a case of leiomyoma of the bladder, a benign tumor that accounts for 0.43% of bladder tumors. The literature is briefly reviewed. METHODS/RESULTS: A 64-year-old male with prostatic syndrome is described. The preoperative evaluation showed bladder lithiasis and signs compatible with prostatic hypertrophy, but no evidence of a bladder tumor. Endoscopic evaluation, however, revealed a tumor in the bladder neck. Transurethral resection of the tumor, prostate and endoscopic lithotripsy of the bladder were performed. The anatomopathological findings showed leiomyoma of the bladder. The postoperative course was unremarkable. CONCLUSION: Leiomyoma of the bladder does not present specific symptoms and is frequently an incidental finding. The diagnosis is based on the results of the anatomopathological analysis of the specimen. PMID- 11213400 TI - [Epidermoid carcinoma of the scrotum]. AB - OBJECTIVE: To analyze the therapeutic approach in epidermoid or squamous cell carcinoma of the scrotum, a rare tumor that is of interest for clinical and historical reasons. METHODS/RESULTS: A case of epidermoid carcinoma of the scrotum is described. The patient had undergone urethroplasty in 1972, using preputial free graft, according to the technique of Ben Johnson. Right scrotectomy and orchidectomy were performed and partial urethrectomy with inguinal lymphadenectomy 6 weeks later. At 24 months' follow-up, the patient has no tumor recurrence. CONCLUSION: Malignant tumors of the scrotum are rare. Squamous cell carcinoma is the most frequent tumor type. Radical surgery with inguinal lymphadenectomy is the treatment of choice. It must be distinguished from verrucous carcinoma, a tumor that requires a different therapeutic approach and for which radical surgery is not indicated. PMID- 11213401 TI - [Giant fibroepithelial polyp of the ureter]. AB - OBJECTIVE: To report a case of giant fibroepithelial polyp of the ureter and review the literature with special reference to the diagnosis and treatment of this benign condition. METHODS: A young male patient with a nonfunctioning left kidney caused by a giant fibroepithelial polyp of the ureter is presented. The diagnostic methods and treatment options are discussed. RESULTS: Following the diagnosis of obstructive uropathy with loss of left renal unit function, a left nephroureterectomy was performed which revealed a giant polypoid mass. CONCLUSION: Fibroepithelial polyp of the ureter is a benign condition that is difficult to diagnose with current endoscopic techniques. Endoscopy should be the first therapeutic option if loss of renal function is not irreversible. PMID- 11213402 TI - [Leiomyoma of the bladder]. AB - OBJECTIVE: To present an additional case of leiomyoma of the bladder, a rare tumor that is frequently discovered incidentally, and to review the few cases reported in the Spanish literature, with special reference to the clinical aspects, complementary tests and treatment. METHODS: A case of leiomyoma of the bladder in a patient who had come to deliver after a full-term pregnancy is presented. Routine physical examination on admission revealed a tumor in the anterior aspect of the vagina. Ultrasound, radiological and endoscopic studies were performed. The Spanish literature is reviewed with special reference to the clinical aspects, complementary tests and treatment. RESULTS: After the diagnosis of a bladder tumor had been confirmed and the effects on the adjacent structures determined, TUR biopsy was performed. The anatomopathological analysis demonstrated leiomyoma of the bladder. CONCLUSION: The ultrasound and radiological images of leiomyoma localized to the bladder are sufficient to suspect the nature of the lesion, but the definitive diagnosis is based on the anatomopathological findings. The choice of the type of surgery, open or endoscopic, is based on tumor localization and size. PMID- 11213403 TI - Intraoperative penile erection. AB - OBJECTIVE: Penile erection following epidural anesthesia is an infrequent occurrence of unclear etioogy. It is very troublesome to perform the procedure during penile erection and attempting it leads to various complications. Three such cases are reported herein. The literature on the pathophysiology and management of intraoperative penile erection is discussed. METHODS: Eighteen hundred patients who received epidural anesthesia for various transurethral procedures like cystoscopy, ureterorenoscopy, transurethral resection of prostate and bladder tumors form the clinical material. RESULTS: Out of 1800 cases, we have encountered penile erection only in three cases. Two cases were managed with local application of cold saline and cold sponging followed by terbutaline. The third case could be managed with local application of cold saline and cold sponging of scrotum and penis. Afterwards the procedure could be performed safely. CONCLUSION: The pathophysiology and management of intraoperative penile erection is poorly understood. With the onset of erection during an operative procedure, the anesthesiologist must quickly initiate the therapy, as duration of erection is the critical factor in the detumescence of the penis. PMID- 11213404 TI - Equivocal mammographic findings. A pictorial essay. PMID- 11213405 TI - [Some thoughts about the ethics of radioprotection]. PMID- 11213406 TI - [CT findings in fire arm injuries of the pelvis. Personal experience]. AB - PURPOSE: We investigated the yield of CT in firearms wounds with pelvis involvement by evaluating the CT features of pelvis, bone walls, and associated injuries, if any. CT plays a major role, while conventional radiography remains an important integration in the workup of pelvis bone injuries. MATERIAL AND METHODS: We report a retrospective series of pelvis gunshot wounds studied with CT in a 5-year period; the patients were all men, with a mean age of 38 years (range 18-56). When only the pelvis was involved, CT was performed from the transverse umbilical plane to the pubis, in order to include the continuous abdomen. We used an intravenous contrast agent to study the aorta and its iliac branches, pelvic vessels, active hemorrhagic effusions and bladder filling. RESULTS: Penetrating firearms wounds were found in 21 cases and perforating ones in 7. In the penetrating wounds, the bullet course was most frequently (75%) stopped by the pelvic bones, with retention and CT visualization within muscular and bone structures. The incidence of bone injuries, especially crash wounds, was high, with 18 cases (64%). In both types of wounds with anterior course, we demonstrated bladder perforation in 2 cases, vascular damage in 2 and perforation of intestinal loops in 6. DISCUSSION AND CONCLUSION: Paradoxically, pelvic bone fractures may be "protective" for the pelvic content; however the involvement of large arteries and veins and multiple perforations of intestinal loops are no less dangerous than the upper abdominal wounds. CT is an important diagnostic tool that permits accurate and prompt evaluation of pelvic organs such as intestine, bladder and bone structures. Thus, CT permits prompt assessment of pelvic structures involvement by firearms wounds, which provides the clinician with useful imaging findings of bullet damage. PMID- 11213407 TI - [The current state of the diagnostics of breast diseases in Lombardy]. AB - PURPOSE: The SIRM study group for senology in Lombardy set the following goals: to quantify the number of radiologist working in public radiology centers and in private credited hospitals in Lombardy; to quantify the number of radiologists working in diagnostic senology and the mean time they devote to this field; to survey the diagnostic equipment used for senology purposes and check its adequacy. MATERIAL AND METHODS: We considered 58 centers of senology diagnostic imaging in the radiology departments of general hospitals in 8 Lombardy provinces. First we evaluated the screening programs for early breast cancer detection carried out with clinical mammography. All data were evaluated with reference to female residents aged 40 to 69, to the average adherence rates reported in the literature, to the protocols adopted in different centers relative to the examination frequency. Mammography was always associated with a physical examination and then the patient was submitted to radiological investigations to make the final diagnosis. The form we used for data report is summarized in Table I. RESULTS: In the centers for diagnostic senology we surveyed in 1998, in all 182,724 mammograms, 58,686 breast US examinations and 7,097 needle biopsies for cytology or microhistology were performed; 35.5% of the female population which should have been screened actually underwent the examination and 32.6% of them was also submitted to breast US, while 3.88% underwent FNAB. Sixty-three mammographic units and 62 US units were operated by 152 radiologists. An average 2,900 radiographic investigations per mammographic unit were performed yearly. Each radiologist reported an average 1,202 mammograms a year. Refer to the tables for detailed data reporting by province. Thirty-six per cent of radiologists presently reads more than 1,500 breast examinations a year. The radiologists working in diagnostic imaging in senology devote an average 20% of their working time to this field. As for the technical adequacy of mammographic and US equipment relative to some reference levels reported in detail in the paper, only 42% of the former and 48% of the latter were up to standards. DISCUSSION AND CONCLUSIONS: Despite the massive work done in the field of senology, the estimated needs of the female population have not been met yet, given the increased demand for senologic examinations and women's growing awareness of the need of early breast cancer diagnosis. The answer to this problem lies in a political health care policy that should promote the current clinical programs increasing both instrumental and human resources. Alternatively screening programs could be planned on a regional basis, with the pro of reaching a larger female population and that of a more homogeneous methodological approach. Our data indicate that breast cancer detection is best achieved with clinical and screening tools: the former can be easily promoted in a short time and could thus make our first goal, while the latter, which is more complex, could be implemented later. Thus, a growing clinical activity could make a very good basis for high quality breast screening programs. Finally, it is necessary to guarantee high quality standards for equipment, methods and training of medical and nonmedical staff. PMID- 11213408 TI - [Radiologic analysis of interval cancers in the screening program called Florence Woman Project]. AB - PURPOSE: The aim of the present study was to provide data on interval cancer incidence after the first round of the screening program in the city of Florence, and to provide and discuss the results of the review of previous screening mammograms. MATERIAL AND METHODS: The screening program "Progetto Firenze Donna" involves all women age 50 to 69 years resident in the city of Florence. In the interval from the end of the first and the start of the second screening round 51 interval cancers were identified, of which 41 were available for radiological review. Films were reviewed by expert screening radiologists, not involved in the program and blinded to the final diagnosis, according to the review criteria recommended by the UK Guidelines for radiologists (blind and informed review). RESULTS: Sensitivity (screening errors/total) was different among blind reviewers (reader A = 7.3%, reader B = 14.6%), as well as specificity which shows an inverse pattern (reader A = 98.4%, reader B = 97.6%). Informed review classified 5 cases as "screening error" (12.2%), 11 as "minimal sign" (26.8%) and 25 as "occult" (61%). Informed review classified a higher proportion of cases as "minimal sign" (minimal abnormalities are better perceived with the knowledge of the site and the pattern of subsequent cancer). DISCUSSION AND CONCLUSIONS: Analysis of interval cancers is fundamental for the quality control of a screening program. According to this experience, informed review tends to overestimate "minimal signs" in the cancer site and should not be used (or "minimal signs" should be anyhow assumed as negative). Identification of interval cases as "minimal signs" may be influenced by individual variability. Standard criteria should be adopted to identify and review/classify interval cancers to allow comparisons between different programs. PMID- 11213409 TI - [Pleural and parenchymal lung diseases from asbestos exposure. CT diagnosis]. AB - INTRODUCTION: We report the CT findings of parenchymal and pleural diseases in a group of patients with a history of asbestos exposure, excluding lung cancer (which is not typical in this subjects) and asbestosis (which is a parenchymal fibrosis). MATERIAL AND METHODS: We retrospectively reviewed a series of CT examinations (conventional, helical and high resolution scans) of 21 patients examined from 1995 to 1999. They had pleural plaques (10), round atelectasis (2) and malignant pleural mesothelioma (9). All patients had a history of direct or indirect asbestos exposure, except one with malignant pleural mesothelioma. We evaluated the following CT findings: nodular, plaque or uniform pleural thickening; pleural calcifications; pleural thickening less or greater than 1 cm; pleural margins (regular, polycyclic, spiculated); localization (uni/bilateral hemithorax); distribution (upper, medium or lower region); pulmonary, mediastinal and diaphragmatic involvement; fissural involvement; pleural effusion; lymph node enlargement; lung mass with the comet-tail sign; lung volume (normal, reduced, increased). RESULTS: Pleural plaques were always bilateral and less than 1 cm thick, with calcifications in 80% of the cases. Margins were always regular, polycyclic in 40% of the patients and never irregular. The pulmonary pleura in the mid-chest was involved in cell cases the diaphragmatic pleura in the 50% of the cases and the upper and lower regions in 60% and 80% of the patients, respectively. Round atelectasis (3 cases in 2 patients) was always shown as a parenchymal mass in the lower lobes, posteriorly or posteromedially, with adjacent pleural thickening; its diameter ranged 4.4-6 cm and there was the comet tail sign. In malignant pleural mesothelioma we always found pleural effusion, with unilateral pleural effusion being the only sign in 2 patients. Other findings were pleural nodules (77.7%), with spiculated (22.2%) and polycyclic (77.7%) margins, more than 1 cm in diameter. The disease was always unilateral. The parenchymal pleural was involved in 77.7% of the cases while the mediastinal and diaphagmatic pleura were involved in 44.4% of the patients. Fissural involvement was demonstrated in 66.6% of the patients. Lymph nodes were enlarged in 66.6% of the cases. The volume of the affected hemithorax was increased (22.2%), decreased (44.4%) or normal (33.3%). DISCUSSION AND CONCLUSIONS: The presence of pleural plaques is a specific sign of asbestos exposure. Round atelectasis may also indicate asbestos exposure, but it can be found in many diseases with pleural inflammation, such as tuberculous effusion, trauma, pulmonary infarct, congestive heart failure, coronary artery bypass. The CT patterns of these two diseases are typical and no other finding is necessary to confirm the diagnosis. CT-guided needle biopsy is needed only if the round atelectasis has an atypical appearance on CT images, that is without the comet tail sign. Malignant pleural mesothelioma is strongly associated with previous occupational exposure and presents typical CT findings only in an advanced stage (irregular and nodular pleural thickening, pleural effusion, mediastinal and pulmonary contraction for tumor encasement, parenchymal and lymph node metastases), but the differential diagnosis with pleural metastatic disease can be difficult. CT plays an important role in tumor assessment but biopsy is necessary for lesion characterization. PMID- 11213410 TI - [Radionuclide imaging in oral implantations. Personal experience in maxillary sinus elevation]. AB - PURPOSE: Presently nuclear medicine techniques are not very popular in oral implantology, but they can play an interesting role in this surgical field too. In particular bone scan with 99mTc-MDP allows to evaluate the function of oral implants and the survival of bone grafts. We report our experience with skull bone scan in maxillary sinus lifting. MATERIAL AND METHODS: We performed a three year follow-up on 13 patients treated with inlay-one stage uni- or bilateral sinus lifting with a mixture composed of 90% bovine bone powder and of 10% small bone splinters and autogenous fibrin glue. We performed imaging studies and quantitated implant MDP uptake from the mean values at the surgical site to the 5th neck vertebral ratio (M/V index). The M/V index was also statistically compared with the one measured in 13 patients with severe resorption of distal upper dental arches (bone height less than 0.5 cm) and in 63 patients with normal dental status. Scintigraphic data were interpreted in the light of clinical, radiological and histologic findings. RESULTS: All oral implants appeared to be fixed and radiographs showed good positioning and bone adhesion; bone height exceeded 1 cm. Peri implant biopsy material was formed by normal mature bone tissue without bovine bone granules, necrotic areas and inflammatory cells. The highest bone activity (M/V index: 1.54-2.57) was observed 1-4 months after sinus lifting. Then MDP uptake decreases and 18 months after surgery radionuclide uptake in maxillary arches is homogeneous, with M/V values of 0.81-0.88. The average M/V value in the 18 surgical sites was clearly higher than in the resorbed (1.44 vs 0.64; Kruskall-Wallis ANOVA test; Dunn's method; p < 0.05) and normal (1.44 vs 0.73; p < 0.05) maxillary arches. DISCUSSION AND CONCLUSIONS: 99mTc-MDP can show the transformation of newformed into mature bone and then allows in vivo visualization of implant osteointegration. The importance of our work lies in the use of radionuclide imaging to assess both the function of oral implants inserted by a complex surgical technique and the expected bioactive properties of the filling mixture. Nevertheless the strong active autogenous compounds do not permit to detect the real agent of local bone induction. An interesting finding is that implant stability is biologically gained 18 months after intervention and that the uptake index facilitates comparison of sequential scans and confirmation of local bone growth. Therefore high MDP uptake by the implant 2-3 years after surgery can suggest mechanical or septic bone injury which can lead to implant failure if not treated promptly. In conclusion we believe that quantitative bone scan is a valid diagnostic tool in the follow-up of oral implants inserted with sinus lifting, though our experience needs confirmation on larger series and new research is warranted to understand the real mechanisms of assisted bone regeneration. PMID- 11213411 TI - [Abdominal pain and bowel dysfunction: the diagnostic role of ultrasonography]. AB - PURPOSE: To evaluate the role of intestinal ultrasound (US) in differentiating organic from functional bowel disease. MATERIAL AND METHODS: We examined with abdominal and intestinal US 313 consecutive outpatients presenting abdominal pain and bowel dysfunction, lasting more than 3 months, with no symptoms or signs of alarm and with no previous diagnosis of organic disease. Our population consisted of 191 women and 122 men, with average age at diagnosis of 36.5 years; 236 of these patients had irritable bowel syndrome, 61 Crohn's disease, and 16 ulcerative colitis. Intestinal wall thickness exceeding 7 mm was considered diagnostic for inflammatory bowel diseases. We compared US findings with the diagnosis made with the conventional diagnostic workup of radiological and endoscopic examinations. RESULTS: Sensitivity of intestinal US for diagnosis of inflammatory bowel diseases was 74% and specificity 98% (respectively 84% and 98% for the diagnosis of Crohn's disease and 38% and 98% for ulcerative colitis), and positive and negative predictive values were both 92%; efficacy was also 92%. The likelihood ratio was 35 if US was positive for inflammatory bowel diseases and 0.26 if bowel wall thickness was less than 7 mm. Diagnostic efficacy was 95% for Crohn's disease and 94% for ulcerative colitis. DISCUSSION: Intestinal US proved to be a valuable tool in diagnosing Crohn's disease. As the first step examination US can show the disease site and suggest further instrumental tests. CONCLUSIONS: In our experience intestinal US is an important diagnostic examination for the approach to young patients without symptoms or signs suggestive of organic diseases and can help avoid invasive instrumental examinations. PMID- 11213413 TI - [Radiologic investigation of external rectal prolapse. Assessment in 48 patients with defecography, seven of them also with dynamic CT of the pelvis]. AB - PURPOSE: To report our personal experience in 48 patients with external rectal prolapse examined with defecography, evaluating radiological signs and the indications for surgical treatment. We also report the results of 7 patients with severe prolapse submitted to dynamic CT of pelvis. MATERIAL AND METHODS: The findings relative to 48 patients suffering from external prolapse, 27 women and 21 men, (mean age 58 years), were retrospectively reviewed. In our study protocol the patient is made to sit on a defecographic commode with the pelvis in lateral projection and radiographic images are acquired at rest, on contraction and on evacuation. Dynamic CT of pelvis with axial and coronal scans of the pelvic floor was carried out in 7 patients with severe prolapses. Twenty-six of 48 patients underwent rectopexy. RESULTS: The main symptoms were anorectal and perineal weight sensation (93%), perineal disturbance in the sitting position (91%) and anorectal pain extended to sacral area (83%). Manometry, which was performed in 36 cases, showed a rectoanal inhibitory reflex evokable at high volumes of air, especially in incontinent subjects. Defecography demonstrated external rectal prolapse in all cases; rectal intussusception in 32, mucosal prolapse in 30, abnormal widening of the anorectal angle in 24 (16 of them were incontinent), rectocele in 22 and perineal descent syndrome in 16 cases. DISCUSSION AND CONCLUSIONS: External rectal prolapse is sometimes a dynamic progression of a rectal intussusception. In anorectal intussusceptions, the invaginatum involves the anal canal, thus causing the external prolapse. Defecography clearly shows the continuation of invagination out of the anus, with the formation of prolapse. Dynamic CT proved accurate in detecting the rectum morphology, but added no further information to defecography, except for the diastasis of anosphincterial muscles. Therefore, we conclude that defecography is the method of choice, though complementary to other instrumental techniques such as manometry, electromyography and endoscopy, in the diagnostic workup of these patients. Moreover, it can recognize other alterations, such as incontinence and rectocele, which can be submitted to surgical correction with rectopexy. PMID- 11213412 TI - [Gastric tumors with fatty components. CT findings and differential diagnosis]. AB - PURPOSE: To assess the role of CT in diagnosing and characterizing gastric fatty tumors. MATERIAL AND METHODS: We reviewed the CT scans of 16 patients (8 men, 8 women, mean age 52 years) with gastric fatty tumors (11 lipomas, 3 liposarcomas, 1 angiolipoma, 1 teratoma) examined from 1990 to 1999. The differential diagnosis considered primary and secondary lipomatosis, carcinoma engulfing the perivisceral fat and thus mimicking a liposarcoma, mesenchymal gastric and primary peritoneal tumors. RESULTS: Lipomas involved the fundus (7/11), the body (3/11), the antrum (1/11). Multifocality was found in one case. Lesions size ranged 25 to 65 mm (mean 35 mm). All the lipomas showed homogeneous structure with negative (-30 -100) HU values. A pseudocapsule was demonstrated in 7/11 cases. No infiltrative growth was demonstrated. The angiolipoma located in the fundus showed a vascular component with strong contrast enhancement. All the liposarcomas were bigger than 10 cm and there was a strong correlation between pathologic specimen and CT findings. The differentiated liposarcomas showed the classic heterogeneous fatty density; on the contrary the myxoid and the pleomorphic types showed an aspecific structure with necrotic/cystic changes, mostly demonstrated in the myxoid type. The teratoma was a solid mass with fatty, solid, necrotic and calcified components. CONCLUSION: CT allows the diagnosis and characterization of gastric fatty tumors. The preoperative diagnosis of lipomas plays a major clinical role because it often makes surgery unnecessary. PMID- 11213414 TI - [Nonobstructive residual mucocele of the cystic duct. Reassessment of complications in our 13 years' experience with liver transplantation]. AB - PURPOSE: We reassessed the incidence of mucocele of the residual cystic duct in our series of orthotopic liver transplantation (OLT) patients. MATERIAL AND METHODS: We examined a series of 283 liver transplants with end-to-end choledocho choledocal anastomosis (263 patients, 163 men and 80 women, 24-65 years old), performed at the II Surgical Department of the University of Bologna from May 1986 to April 1999 and subsequently followed-up in our Institute. All patients were examined with gray-scale and color Doppler US and some also underwent CT and CT cholangiography. RESULTS: An anechoic ovoidal structure just before the portal vein and in proximity of the main bile duct was found in 13 patients. US and CT findings, the latter when available, led us to make a diagnosis of nonobstructive mucocele of the cystic duct. The radiological diagnosis was eventually confirmed by clinical and surgical findings. DISCUSSION AND CONCLUSIONS: In our series the incidence of this complication was 4.5%, a slightly higher value than those reported in the literature. Cystic duct mucocele cannot be considered an uncommon complication and should thus be more carefully searched for by operators. In our experience this complication never required reoperation for cholestasis. PMID- 11213415 TI - [Renal arteriovenous fistulas after renal biopsy. Percutaneous embolization]. AB - PURPOSE: We report our experience relative to transcatheter percutaneous embolization of post-biopsy renal intraparenchymal arteriovenous fistulas in patients with chronic renal insufficiency. MATERIAL AND METHODS: We observed 5 patients affected with post-bioptic fistulas for possible embolization. In three cases the symptoms were represented by intermittent macro-microhematuria; one patient had hypertension of nephrovascular origin and one patient was asymptomatic. In all cases we performed angiography and it was possible to catheterize the peripheral afferent branch of the fistula with a superselective technique using a hydrophilic guide of 0.035 F and a hydrophilic Cobra catheter of 4-5 F. The occlusion was obtained by the positioning of Granturco metal coils: in 1 case we adapted a coil of 3 mm diameter and 1 cm length; in 3 cases 2 coils of 3 mm and in 1 case 2 coils of 3 mm and 1 coil of 5 mm diameter and 1 cm length were necessary. The success of the procedure was always checked with an immediate angiogram and color Doppler US after 48 hrs. RESULTS: The diagnosis of arteriovenous fistulas was always confirmed by a preliminary angiography that demonstrated the normal anatomic disposition of the renal arteries except in one case in which the fistula was fed by a peripheral branch originating from an inferior polar artery. All the lesions were localized in the inferior pole, the site of biopsy, and ranged from 3 mm to 2.5 cm in diameter. We never had any difficulties in the positioning and placement of the coils. The arterial occlusion and exclusion of the fistula was accomplished in all cases. The induced parenchymal loss ranged from 10 to 30% of the renal volume. There was a complete disappearance of symptoms in 3 of the patients, with hematuria without any modification of the blood pressure values in the patient with hypertension. Considering the patient status renal function did not worsen after the embolization. Each patient was followed-up with color Doppler US every two months. CONCLUSIONS: The intrarenal arteriovenous fistula represents a relative frequent complication of renal needle biopsy in patients with arterial hypertension and nephroangiosclerosis as risk factors. Embolization is a valid alternative therapeutic option to surgical treatments. The use of small size catheters permits the successful embolization also of peripheral lesions, reducing the induced parenchymal ischemia. We believe that among the embolization material available metal coils represent a valid solution as they are easily positioned and permit definitive occlusion without any risks of systemic venous microembolization. PMID- 11213416 TI - Correlation between pretreatment prognostic factors and lymph node metastases in endometrial adenocarcinoma. Clinical application. AB - PURPOSE: To evaluate the prognosis of stage I endometrial adenocarcinoma, which differs by various prognostic factors. Some of them (tumor grading, histotype, myometrial infiltration, the latter evaluated with Magnetic Resonance Imaging) can be assessed before surgery. These prognostic factors correlate with patient survival and the presence of lymph node metastases. MATERIAL AND METHODS: We used tumor grading, histotype, myometrial infiltration for the preoperative and prospective classification into a low- and a high-risk group of 80 patients with endometrial adenocarcinomas stage I. Low-risk patient [group A: G1-G2, pure adenocarcinoma involving the inner portion of the myometrium (M0-M1)] underwent surgery without lymph node resection, while high-risk patients [group B: G3, pure adenocarcinoma with deep infiltration of the myometrium (M2) and/or clear cell, serous papillary, adenosquamous carcinomas] had pelvic and lumboaortic lymphadenectomy. The minimum 36 months' follow-up (median: 61 months) was requested for all patients. RESULTS: Histotype evaluated by dilatation and curettage and hysteroscopic and/or office biopsy, had 100% agreement with tumor histotype. Tumor grading was in agreement in 72/80 patients (81%). The grade of myometrial infiltration was confirmed in 72/80 cases (81%). Eight misdiagnoses were divided in over--(4 cases) and under--(4 cases) estimated infiltration. All 16 mistakes resulted in 10 inclusion in the wrong risk group (8 in the low-risk and two in the high-risk group). Surgical-pathological staging did not change the prognosis but only staging in 6 preoperatively high-risk group. CONCLUSIONS: This initial study confirms the importance of prognostic factors in the treatment of endometrial adenocarcinoma, as well as that of the different surgical choices which can be made after correct pretreatment prognosis. PMID- 11213417 TI - [Optimization of lymphoscintigraphy in sentinel node biopsy in the staging of malignant melanoma]. AB - PURPOSE: To optimize the lymphoscintigraphic procedure in the staging of malignant cutaneous melanoma. MATERIAL AND METHODS: Fifty-five patients (21 men and 34 women) were enrolled. Breslow thickness of the lesions ranged 0.75-1 mm (Clark III-IV) to 1-4 mm. Lymphoscintigraphy was performed with a large-view gamma camera equipped with a low-energy general purpose collimator, two weeks after melanoma excision. A single perilesional dose of 30-50 MBq nanocoll-Tc99m (volume 0.2-0.3 mL) was injected 18 hours before surgery (6 hours in head localizations). After injection a gentle local massage was applied. A planar static scintigraphy (matrix 512 x 512, pre-set time 5 min) in anterior and/or oblique view(s) was obtained 5-10 min after radiotracer injection. The skin projection of the first node was stained with an external radioactive marker. Fifteen minutes before surgery a blue-vital dye was injected around the lesion. A radioguided biopsy of the sentinel node was performed. RESULTS: The site of the sentinel node was typical in 80% of patients. Two or three nodes were identified in 20% of patients. An unexpected node site was detected in 9% of patients. The total rate of micrometastasis to the sentinel node was 14.7% but significant differences were observed relative to the melanoma thickness. CONCLUSIONS: Preoperative scintigraphy increases the accuracy of sentinel node identification in unusual lymphatic drainage pathways, in unexpected sites and in fast lymphatic drainage. Radioguided biopsy reduces surgical time, requires only local anesthesia and permits shorter hospitalization. PMID- 11213418 TI - [A method for quantitative evaluation of the physical quality of radiologic devices]. AB - INTRODUCTION: The evaluation of the quality of a radiological device depends on both clinical judgement about diagnostic imaging and physical judgement about technical performance. The latter is the final result of a set of measurements of several physical quantities. The aim of the present paper is to make a synthesis of such measurements through a parameter whose comparison with a threshold value would allow to establish whether a given radiological machine is acceptable from the point of view of physical quality. MATERIAL AND METHODS: The parameter, which we called quality index, was obtained by considering, for each operating condition, the values of physical quantities which exceed their limits and by giving them a different weight, depending on their influence on image quality, patient dose, or both. Further analysis led to assign a gravity index to such quantities as a function of the extent of the discrepancies with respect to their limits. RESULTS AND DISCUSSION: The method was illustrated through the example of a simple radiological equipment with two separate hypothetical cases corresponding to different degrees of fault gravity. The method gave very different values of quality index, according to the extent of discrepancies found in the two cases. We gave suggestions about the way to follow in order to determine a proper threshold value for each kind of equipment. The invariance of the method with respect to the choice of the physical quantities and their limits was also shown. CONCLUSIONS: The proposed method appears to be useful because it makes a synthesis, through a single parameter, of a series of measurements of several physical quantities and allows to discriminate, through direct comparison with a threshold value, about the physical quality of a radiological device; in addition, it may be easily implemented into programs for the automated analysis of quality controls. The quality index may contribute, together with some other parameters to be defined in a forthcoming paper, in establishing a quantitative criterion in order to define equipment replacement priorities within the context of the technological improvement requested by the laws currently in force. PMID- 11213419 TI - [Unusual location of villonodular tenosynovitis. Three case reports and review of the literature]. PMID- 11213420 TI - [Ossifying pleural metastases from osteosarcoma. CT evidence in two cases]. PMID- 11213421 TI - [Comprehensive imaging of hepatic adenoma simulating focal nodular hyperplasia. A case report]. PMID- 11213422 TI - [Renal adenocarcinoma in childhood. A case report]. PMID- 11213423 TI - [Idiopathic retroperitoneal fibrosis diagnosed with color Doppler echography and ultrasonography-guided fine needle biopsy, a case report]. PMID- 11213424 TI - [Thyroid gland involvement in acute leukemia. Ultrasonographic aspects of a case]. PMID- 11213425 TI - [Lymphoma of the breast: contrast agent transit time in color-Doppler ultrasonography. A case report]. PMID- 11213426 TI - Comparative in vitro evaluation of nimesulide-containing preparations on the Italian market. AB - Nimesulide is a quite popular non-steroidal anti-inflammatory drug (NSAID), which has been demonstrated to preferentially inhibit cycloxygenase-2 (COX-2), thus exerting milder gastrointestinal and renal side effects. Apart from the original products (Aulin and Mesulid), several copy and generic nimesulide-containing preparations are presently available on the Italian market. Generics are defined by the World Health Organization (WHO) as interchangeable multi-source pharmaceutical products and, according to international regulatory issues, their bioequivalence to an already marketed reference product has to be proven. Due to its physico-chemical properties, and in particular to the low solubility, nimesulide appears to be a critical molecule from a biopharmaceutical point of view. On the basis of these premises, the aim of the present work was to perform a comparative evaluation of tablets in vitro behaviour for the best-selling copy (Sulidamor) and generic (Nimesulide Dorom) in reference to the original products. The results provided by the dissolution test pointed out statistically significant differences in the in vitro behaviour displayed by the original products on one hand and by the copy as well as generic preparations in exam on the other. PMID- 11213427 TI - Effect of dissolution fluid and presence of hog intestinal barrier on the dissolution of theophylline from bioadhesive granules. AB - The effect of dissolution fluid and the presence of a natural barrier (hog intestine) on the release of theophylline from some bioadhesive granules is presented. A higher quantity of the drug was released in simulated intestinal fluid (SIF) than O. IN HCl. When a hog intestine was used as the diffusion barrier, the availability of the drug through the barrier into the sink solution was low, ranging from 20-35%. PMID- 11213429 TI - The compliance of the community and private pharmacies' patients. AB - This issue is an attempt to expose the extent of compliance, respectively of non compliance among the patients of the community and private pharmacies in Sofia. The authors make an attempt to elucidate the factors that influence upon the non compliance of the patients in order to increase the rate of compliance among them. The results of the analysis of the received data show that the level of the compliance is 69% among the studied patients. Despite the presented adequate level of compliance among the patients, there are possibilities for the individualisation of the treatment, for supply with more information and for improvement of the patient-physician and patient-pharmacist interrelations. PMID- 11213428 TI - The absorption of protein hormones through rabbit rhinal mucosa. AB - The absorptions through rabbit rhinal mucosa of the following hormones with a protein-peptide structure: thyrotropin-releasing hormone, insulin, and prolactin, were compared. A very high negative correlation between the molecular weight of the hormones and the total amount of the hormones molecular weight of hormones absorbed through the rhinal mucosa (r = 0.973) was found. Within 2 hours of the experiment, 33.94% TRH, 23.96% INS, and only 11.01% PRL, were absorbed from the administered dose. PMID- 11213430 TI - A comparative study of modified starches in direct compression of a water soluble drug-chloroquine phosphate. AB - Some in vitro properties of chloroquine phosphate tablets formulated with four modified starches were investigated. The drug was formulated as tablets containing 250 mg of chloroquine phosphate and produced by the direct compression technique. The starches were isolated from maize, zea mays, rice, Oryza sativa, cassava, Manihot esculenta and cocoyam, Zanthosoma sagittifolium. They were modified through physicochemical process, Sta-Rx 1500, a directly compressible starch was used as basis for comparison. The hardness of the chloroquine tablets generally decreased to a minimum with all the modified starches at concentration level of 40% and with maximum hardness obtained when their concentrations were increased to 80%. The least hardness values were obtained with modified cocoa yam starch while the highest hardness values were obtained with modified rice starch. Modified rice and cassava starches produced chloroquine tablets that exhibited higher mechanical properties than those of modified maize starch, cocoayam starch and Sta-Rx 1500. On the basis of dissolution profile of chloroquine phosphate tablets, the modified starch samples were ranked in order of increasing dissolution as modified cocoayam maize Sta-Rx 1500 cassava rice starch sample. The release rate of chloroquine was found to be dependent on the physico-chemical properties of the individual modified starch granules such as particle size and degree of gelatinization. PMID- 11213431 TI - Assay of fluoxetine hydrochloride by titrimetric and HPLC methods. AB - Two alternative methods were proposed to assay Fluoxetine Hydrochloride: a titrimetric method and another by HPLC using as mobile phase water pH 3.5: acetonitrile (65:35). These methods were applied to the determination of Fluoxetine as such or in formulations (capsules). The titrimetric method is an alternative for pharmacies and small industries. Both methods showed accuracy and precision and are an alternative to the official methods. PMID- 11213432 TI - Chromatographic detection of cimetidine and famotidine using chloranilic acid as a spray reagent. AB - Qualitative determination of cimetidine and famotidine by TLC using chloranilic acid as the detecting spray reagent was carried out in different elution systems. On spraying, coloured spots corresponding to the drugs were formed which were stable for over three hours. In a particular solvent system, a commercial sample gave the same Rf value as its corresponding pure reference sample without any interference from the excipient. PMID- 11213433 TI - Synthesis and biological activity of 6-substituted-3-[2-(5-substituted-2 furfurylidenehydrazino)-4-thiazolyl] coumarins. AB - A series of coumarin-derivatives (5) were synthesized by the reaction of 5 substituted-2-furfuraldehyde thiosemicarbazones with 3-bromoacetyl-6-substituted coumarins. The structures of newly synthesized compounds were confirmed on the basis of their elemental analysis, NMR and mass spectral data. Some selected compounds were screened for their antibacterial activity employing disc diffusion technique. PMID- 11213434 TI - Lipid peroxidation in human blood platelets during unstable angina and myocardial infarction. AB - A comparative study on the levels of lipid peroxidation in human platelets has been undertaken in patients of unstable angina and reperfused acute myocardial infarction and matched healthy individuals. Lipid peroxidation increases in these patients, most marked increase were in the patients of reperfused myocardial infarction. PMID- 11213435 TI - A comparative study of aminophylline and acepifylline on reversal phenomenon of anticonvulsant drug efficacy in electroshock model of seizures in rats. AB - The study was designed to compare the proconvulsive activity of two theophylline containing bronchodilating agents, aminophylline and acepifylline and their antagonistic effects to diazepam, phenytoin, MK-801 and carbamazepine in electroshock seizure model in rats. Graded intensity (30-150 mA for 0.2 s) of electroshock was applied to different groups of rats pretreated either with normal saline (0.5 ml, i.p.), graded doses (25-150 mgkg-1, i.p.) of aminophylline, graded doses (70-560 mgkg-1, i.p.) of acepifylline, graded doses of the antiseizure drugs or to rats pretreated with aminophylline (25 mgkg-1, i.p.) + antiseizure drugs or acepifylline (70 mgkg-1, i.p.) + antiseizure drugs. CI 50 +/- s.e.m. value was 88.41 +/- 2.14 mA in saline treated rats. In aminophylline pretreated rats the values were 84.14 +/- 2.03, 68.06 +/- 1.24, 54.28 +/- 1.96 and 39.58 +/- 2.31 mA at 25 mgkg-1 (0.06 mmolekg-1), 50 mgkg-1 (0.12 mmolekg-1), 100 mgkg-1 (0.24 mmolekg-1) and 150 mgkg-1 (0.36 mmolekg-1), i.p. doses respectively. The values were 85.73 +/- 1.09, 64.86 +/- 2.37, 61.58 +/ 1.37 and 60.62 +/- 2.41 mA at 70 mgkg-1 (0.125 mmolekg-1), 140 mgkg-1 (0.25 mmolekg-1), 280 mgkg-1 (0.50 mmolekg-1) and 560 mgkg-1 (1.0 mmolekg-1), i.p. doses respectively for the acepifylline pretreated groups of rats. Diazepam, MK 801, phenytoin and carbamazepine significantly antagonized electroshock-induced seizure in a dose-dependent manner. Subsensitizing dose of aminophylline (25 mgkg 1, i.p.) but not that of acepifylline (70 mgkg-1, i.p.) pretreatment significantly antagonized the efficacy of all the antiseizure drugs. The study highlighted that acepifylline might be safely used in epileptic patients well controlled on antiepileptic drugs. Aminophylline, on the other hand, should be avoided since it might produce breakthrough seizure attacks due to its greater proconvulsive and anti-antiseizure drug effects. PMID- 11213436 TI - Investigation of antimicrobial activity of essential oils of several Macedonian Thymus L. species (Lamiaceae). AB - Antimicrobial activity of twenty specimens of essential oils of eleven Thymus species, naturally occurring in the Macedonian flora, was investigated by agar diffusion and broth dilution methods. Inhibition of growth and microbicidal action was examined on three Gram positive bacteria (Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae). In spite of wide variability in essential oil composition, ranging from traces of thymol to the amount of about 50% thymol in oils, all examined samples of Thymus essential oil possessed strong antibacterial activity. Zones of inhibition of growth (for 25% dilution of oils) was from 10-54 mm in diameters. MICs ranging from 0.012-0.1% while MMCs were from 0.025-0.4% for essential oils that contained large amounts of phenols and 0.2-1.6% for those which contained traces of phenols and large amounts of geraniol, linalool and (Z + E)-citral. PMID- 11213437 TI - Some emulsifying and suspending properties of the mucilage extracted from kernels of Irvingia gabonensis. AB - The mucilage extracted from the kernels of Irvingia gabonensis was evaluated for use as suspending and emulsifying agent. The rheological behaviour of the mucilage was studied and compared to that of tragacanth. As a suspending agent, Irvingia mucilage was compared to tragacanth at various concentrations (0.5, 1.0, 1.5 and 2.0% w/v) in the formulation of sulphanilamide suspensions. At all concentrations the formulated suspensions with Irvingia mucilage gave higher Hu (final sedimentation height) and F (sedimentation volume) values. As an emulsifying agent, the properties of Irvingia mucilage was compared to tragacanth and acacia gum. The emulsions prepared with 0.6, 1.0, and 1.5% tragacanth and Irvingia 'cracked' within six days while that with 12.5% w/v acacia started showing signs of creaming at the tenth day. The emulsion prepared with 2.0% w/v Irvingia mucilage was however stable throughout the six weeks of study. The results indicate that Irvingia mucilage performed better than acacia and tragacanth even at lower concentrations in the formulation of emulsions and suspensions. PMID- 11213438 TI - Eudragit matrices for sustained release of ketorolac tromethamine: formulation and kinetics of release. AB - Matrix type formulations with dicalcium phosphate dihydrate (DCPD) using a polymeric binder (Eudragit RSPM) to obtain controlled release of Ketorolac tromethamine (KT) has been investigated. The drug, DCPD and Eudragit RSPM were granulated using isopropyl alcohol with and without a plasticizer (Diethyl phthalate, DEP). Addition of Eudragit appear to affect the release profile. However, addition of a plasticizer had a significant effect on the rate of release. The release appears to follow first order kinetics and the rate constant decreased linearly with increasing DEP concentration. A directly compressible mixture was also formulated by coating DCPD particles with DEP with and without Eudragit RSPM. PMID- 11213439 TI - [Production and characterization of an atenolol-reticulated povodone tablet]. AB - The production of polymeric complexes in many active drugs with reticulated povidone increased dissolved component percentage. In this work made use a coevaporation technique. Complex formation has been tested by X Ray Diffractometry and Differential Scanning Calorimetry. The percentage of dissolution was determined to the USP XXIII Edition methodology. As can be seen from the results, the Atenolol-reticulated Povidone complexes has greater solubility than the Atenolol mixed with Lactose as excipient. PMID- 11213440 TI - Synthesis of some new phenylthiocarbamoyl 2-pyrazolin-5-ones of pharmaceutical interest. AB - Thiocarbamoylation reaction of 3-methyl-2-pyrazolin-5-one (1a) with two equivalents of PhNCS, resulted in the formation of 1,4-di(alpha phenylthiocarbamoyl)-3-methylpyrazolone 3, which underwent cleavage of the thiocarbamoyl group at position 4 when coupled with aromatic diazonium salts affording 4-arylhydrazono-1-phenylthiocarbamoylpyrazolone (4a-j). Reactions of 4a with chloroacetyl chloride, benzenesulphonyl chloride, piperidine and hydrazine hydrate, resulted in the formation of 8. PMID- 11213441 TI - Syntheses of new 5,6,7,8-tetrahydropyrrolo [2,3-d]azepine ring system. AB - A first synthesis of pyrrolo[2,3-d]azepine ring system starting from pyrrole and perhydroazepine derivatives was reported. In addition, Lansbury's reaction is developed through the use of para-toluene sulphonic acid (p-TsOH) as a new catalyst for this reaction. PMID- 11213442 TI - Distribution and pharmacokinetics of the gonadotrophin releasing hormone analogue (Gn-RH analogue) dalarelin in rats. AB - The dynamics of concentration changes for dalarelin in the blood as well as in organs and tissues at different times from its administration to female rats as a single subcutaneous injection, was observed. Also, the basic pharmacokinetic parrameters were determined. The maximum concentration of dalarelin in the blood (Cmax), which was 261.5 pg/cm3, was observed at the maximum time (tmax) 30 min, after its subcutaneous administration. The simplest equation describing the observed concentration changes for dalarelin in the blood is a tri-exponential equation of an open two-compartment model. The obtained results indicate that dalarelin is selectively captured by the pituitary as well as by the non-specific organs: heart, brain and uterus. It allows us to conclude that it has a wider spectrum of activity. PMID- 11213443 TI - In vitro anti-mycotic activity of some medicinal plants containing flavonoids. AB - Aqueous, ethanolic and petroleum ether extracts of Citrus sinensis L. (Osbeck), Euphrasia officinalis L., Glycyrrhiza glabra L., Matricaria recutita L., Rosa canina L. and Ruta graveolens L. have been studied. The antimycotic activity was evaluated "in vitro" on strains of Candida albicans isolated from clinical samples obtained in the course of acute vaginitis. PMID- 11213444 TI - Investigation of alkylating, antineoplastic and anti-HIV potentials of the chalcones: 2-(3-arylpropenoyl)benzimidazole and their corresponding N1-methyl derivatives. AB - A series of 2-(3-Arylpropenoyl)benzimidazole, 3a-d, and their corresponding N1 methyl analogues, 3e-h, were synthesized from p-substituted benzaldehyde and 2 acetylbenzimidazole or 2-acetyl-1-methylbenzimidazole, respectively. The in vitro alkylating activities of these alpha-beta-unsaturated ketones were investigated using L-cysteine as a model of cellular thioles at pH 7.4 and 37 degrees C. No significant difference between the alkylating activities of 3a-d and 3e-h as expressed from the pseudo first-order rate constants of the reactions of these derivatives with L-cysteine monitored by HPLC. However, significant variations in the rates of alkylation among these derivatives relative to the p-substituted group on the aryl moiety were observed, which is attributable to the electronic parameters of the substituted groups. The in vitro cytotoxic activity provided that the p-nitro derivative; 3d has some selectivity for cell lines of leukemia, renal cancer and breast cancer. The compounds were completely inactive as anti HIV agents. Molecular modeling for all derivatives was undertaken. PMID- 11213445 TI - [Scientific cooperation in the area of criminologic techniques in Europe]. AB - Due to an increased trend toward professionalism on the part of criminals and the globalization of crime the demands on forensic science have increased. These demands can only be met by international co-operation. A priori all areas of forensic science can be recommended as fields where working together is adequate. Co-operation--depending for example on the amount of work required for planned research and development, on the need for harmonization of methods and techniques or on the complexity of the task--is certainly necessary to a varying extent. In institutionalizing co-operation it is not so much a mere increase in the relevant activities that is offered but much more variety of (new) ideas. In doing this, as will be shown in a couple of examples, the use of new information and communication technology in particular should be increased. PMID- 11213446 TI - [Combined suicide by drinking acetic acid with subsequent hanging]. AB - Three late emigrants of German origin from Russia (1 man, 2 women) drank 70- and 86% acetic acid respectively before hanging themselves. In one of the suicides the hanging noose was running across the face. None of the cases presented showed any perioral chemical burns. At autopsy an intense odor of acetic acid was noticeable. The mucosa of the upper digestive tract showed a whitish, grey, brown or black discoloration and was partially detached. In two cases intravascular clotting of blood was discernible in the area affected by the acid; in one case the vessels were imbibed with haemoglobin due to haemolysis. Highly concentrated acetic acid is generally available in the successor states of the former USSR and its use in suicides is thus not uncommon. The legal regulations applying in Germany to the sale of acetic acid and the toxicological data are briefly described. PMID- 11213447 TI - [Criminal and suicidal death with bolt gunshot weapons. An experimental and case contribution]. AB - Authors report on two cases of homicide and another case of suicide, all committed with captive-bolt livestock-stunners. The investigation of skull caps revealed roundish holes at the entry sites which were beveled-out in a paraboloid like manner on the inner aspect. These defects were reproducible in test shots with various strengths of ammunition and different materials as targets. PMID- 11213448 TI - [Discovery of externally unremarkable case of homicide of an infant]. AB - The court-ordered autopsy of an infant who had died 26 days after delivery unexpectedly revealed a fatal head injury. As external inspection of the body had not shown any traces of violence sudden infant death had at first been assumed. At autopsy a linear fracture of the skull and a subdural haematoma was found. Subsequent investigations showed that the father had thrown the baby into the air while playing with it, that he had failed to catch it and that it had fallen downwards heavily hitting the wooden armrest of a couch with the parietal region. As an example of a manslaughter without any external signs of trauma the case illustrates the importance of forensic autopsies in all cases of unexpected death. PMID- 11213450 TI - Culture of the bacterium responsible for Whipple's disease. PMID- 11213449 TI - [Misinterpretation of fetal high voltage and lightning accidents]. AB - From medicolegal practice it is known that in deaths caused by low voltage, electric marks may be absent or inconspicuous so that they may remain undetected during the scene examination. That this may happen even in fatal high-voltage accidents is demonstrated by 4 examples from our own autopsy material. The cases reported shared the following features: The decedents were found outdoors under a high-voltage line with a several metres long conductive object being in the immediate vicinity of the body; no extensive burns as those seen after the impact of an electric arc; inconspicuous electric marks on the hands; clearly visible electrothermal skin lesions limited to body regions covered by clothing (especially soles of the feet). Another case report demonstrates that even fatal lightning accidents are not always recognized correctly. PMID- 11213451 TI - [History of oxygen therapy]. PMID- 11213452 TI - [Biliary epithelium, hepatocytes and oval cells]. AB - Two types of epithelial cells derived from a unique embryonic stem cell coexist in the liver: hepatocytes, which form the liver parenchyma, and cholangiocytes which line intrahepatic bile ducts. Both cell types represent more than 70% and around 3% of hepatic cells, respectively. Initially secreted in the canalicular space formed by the apical domain of hepatocytes, bile is subsequently collected and modified in bile ducts. Both types of epithelia can regenerate as a result of differentiated cell proliferation. However, massive or chronic injury may induce the emergence and proliferation of oval cells, a heterogeneous population of small cells expressing embryonic markers that may subsequently differentiate into hepatocytes or cholangiocytes. Oval cells may also give rise to hepatocellular or cholangiocellular carcinomas. They may derive not only from hepatic cells (including hepatocytes and cholangiocytes themselves), but also from extrahepatic haematopoietic stem cells. PMID- 11213453 TI - [Epidemiology and natural history of cholelithiasis]. AB - Gallstone disease is relatively common, affecting approximately 15% of the population in Europe and North America, but it is benign since its natural history remains asymptomatic in nearly 80% of cases. The stones are predominantly cholesterol derived in 80% and pigmentary in 20% of cases. Recent epidemiologic studies using ultrasound examination have determined the factors favouring lithogenesis, in addition to those that are already wellknown, such as age, obesity, female gender, high blood triglyceride levels and multiparity, the risk is correlated with high, frequent variations in weight, with intake of certain drugs and with alimentary habits. In addition, physical exercise plays a protective role against the development of symptomatic gallstone disease. PMID- 11213454 TI - [Gallstones and their complications]. AB - Gallbladder stones are present in more than 10% of the population in Europe, particularly in women. Most patients are and will remain asymptomatic. No treatment is required. Patients with gallstones and biliary colics should have elective laparoscopic cholecystectomy which can be performed in almost every case. Acute gall-stone cholecystitis is the most severe complication. It should prompt urgent cholecystecomy that can be done by laparoscopy. Other complications such as biliobiliary fistulas have become unfrequent. PMID- 11213455 TI - [Common bile duct stones and their complications]. AB - At the time of cholecystectomy for symptomatic cholelithiasis, 7-20% of patients have common bile duct stones. Nearly one third of them are asymptomatic. Routine cholangiography during cholecystectomy allows the diagnosis and treatment of common bile duct stones during the same operation. Selective indication for the diagnosis of common bile duct stones based on the positive predictive value of indicators limits treatment to symptomatic cases. No single indicator is however completely accurate in predicting common bile duct stones and the natural history of asymptomatic cases is uncertain. Endoscopic stone extraction preceding cholecystectomy is not superior to one-stage surgical treatment. Diagnosis and treatment of common bile duct stones are feasible laparoscopically. Complications of common bile duct stones are cholangitis and acute pancreatitis; if severe, they require specific therapeutic approaches. PMID- 11213456 TI - [Biliary tract cancers]. AB - Biliary tract cancer is the second most common primary hepatobiliary cancer, after hepatocellular carcinoma. The most frequent localisation is the gallbladder. Mean age of diagnosis is 65 years. The exact cause remains unknown despite well documented risk factors. The majority of these tumours are adenocarcinomas. Symptoms, frequently non specific, are occasionally typical including jaundice, right upper quadrant mass or fatigue and weight loss. Magnetic resonance imaging is becoming the main diagnostic tool, replacing retrograde or transhepatic cholangiography. Surgical resection remains the only treatment that may allow long term survival. However, it is possible in only one third of patients. PMID- 11213457 TI - [Cystic dilatation of the biliary tract]. AB - Cystic dilatations of the biliary tree are defined by cysts which communicate with the biliary channels. Caroli's disease is characterized by macroscopic dilatations of segmental bile ducts (who drain the segments of the liver). It is not familial. Kidneys are usually normal. The main symptom is cholangitis. Complications are intrahepatic stones and cholangiocarcinoma. Treatment of cholangitis is antibiotics. In resistant cases, partial hepatectomy (if cysts are localized in one part of the liver) or hepatic transplantation (if cysts are diffuse) should be considered. Congenital hepatic fibrosis is characterized by microscopic dilatations of interlobular bile ducts and portal fibrosis. It is an autosomal recessive disease associated with renal abnormalities. The major clinical manifestation is digestive haemorrhage due to portal hypertension. Caroli's syndrome is the association of Caroli's disease and congenital hepatic fibrosis. Choledocal cyst is characterized by a cystic dilatation of the common bile duct or hepatic duct. The main manifestations are jaundice and cholangitis. Cholangiocarcinoma may occur. Treatment is surgical resection. PMID- 11213458 TI - [Congenital disorders of the biliary ducts]. AB - Congenital disorders of the bile ducts manifesting as neonatal cholestasis, are: biliary atresia, Alagille syndrome and neonatal sclerosing cholangitis. Biliary atresia must be considered as a neonatal surgical emergency: diagnosis and therapeutic intervention should be completed before one month of age. Survival at 10 years is about 70%, 14% without and 56% with liver transplantation. The cause of the disease is unknown. Alagille syndrome is defined by the association of bile duct paucity, pulmonary stenosis, butterfly-like vertebrae, peculiar facies and posterior embryotoxon. JAGGEDI gene mutations have been identified allowing prenatal diagnosis. The diagnosis of neonatal sclerosing cholangitis can only be performed by cholangiography. PMID- 11213459 TI - [Primary sclerosing cholangitis]. AB - Primary sclerosing cholangitis is an uncommon disease, characterized by the progressive destruction of intra and extrahepatic bile ducts. The disease mainly affects males below 40 years of age. Main consequences of the disease are cholestasis, cholangitis, intrahepatic lithiasis, and secondary biliary cirrhosis. In 5-10% of the patients, cholangiocellular carcinoma develops. Diagnosis is based on retrograde cholangiography. There is no specific medical treatment. Liver transplantation must be considered in the end-stage of the disease. PMID- 11213460 TI - [Quantifying quality: the patient's perspective]. PMID- 11213461 TI - [Epithelial skin cancers. Epidemiology, etiology, anatomic pathology, diagnosis, treatment principles]. PMID- 11213462 TI - [Diffuse goiter and thyroid nodule]. PMID- 11213463 TI - [Workplace accidents and occupational diseases. Definitions]. PMID- 11213464 TI - [Mumps. Epidemiology, diagnosis, etiology, prevention]. PMID- 11213465 TI - [T cells and cellular immunity; T receptors (structure, diversity, repertory); differentiation antigens (CD4, CD8); activation; auxillary T cells and immunoregulation; lymphokines (interferons, TNF, IL-1, IL-2, IL-4) and cytotoxicity; concept of cellular immunity deficit]. PMID- 11213466 TI - [Manic syndrome. Diagnostic approach and treatment principles]. PMID- 11213467 TI - Evolution of thioredoxin and redox signaling research: viewpoint. PMID- 11213468 TI - Effect of cAMP on inducible nitric oxide synthase gene expression: its dual and cell-specific functions. AB - The effects of some cAMP-elevating agents on the induction of nitric oxide synthase II (NOS II) were investigated for a macrophage-derived cell line, RAW264.7, stimulated with lipopolysaccharide (LPS) or interferon-gamma (IFN gamma) and the results were compared for the case of vascular smooth muscle cells (VSMC) stimulated with interleukin-1 beta (IL-1 beta). Forskolin, dibutyryl cAMP, and a phosphodiesterase inhibitor, 3-isobutyl-1-methyl xanthine, resulted in an elevated production of nitrite and nitrate, NOS II activities, NOS II mRNA accumulation, and the protein level in RAW264.7 cells stimulated with LPS or IFN gamma. However, the addition of combinations of these reagents decreased these levels in RAW264.7 cells, but enhanced them in VSMC that had been stimulated with IL-1 beta. When intracellular cAMP levels in VSMC were measured, they were elevated by about 100 times more in the forskolin-treated cells, compared to the untreated cells. Stimulated RAW264.7 cells, on the other hand, produced much lower levels of cAMP than VSMC. It is likely that cAMP functions in two opposing directions in terms of NOS II gene induction in RAW264.7 cells in a dose dependent manner. The effects of cAMP-elevating agents on promoter activities of the 5'-flanking region of the mouse NOS II gene were then examined. The promoter activities were enhanced in RAW264.7 cells, even in the presence of all three cAMP-elevating agents. Although the binding of NF-kappa B to responsive elements is essential for the induction of the NOS II gene, cAMP-elevating agents had no effect on NF-kappa B binding to the element, thus eliminating the involvement of NF-kappa B in the suppression of the NOS II gene by high concentrations of cAMP. These data suggest that a putative responsive element to high levels of cAMP is present outside of the region examined in this study. The inhibitory effects of cAMP in RAW264.7 cells would be due to the presence of a negative regulatory factor that is absent in VSMC. PMID- 11213469 TI - Efficiency of selenocysteine incorporation in human thioredoxin reductase. AB - Thioredoxin reductase (TR) is a flavoenzyme, containing one selenocysteine (Sec) residue at the penultimate carboxyl-terminus, that catalyzes the NADPH-dependent reduction of oxidized thioredoxin. Sec is encoded by the UGA stop codon in the open reading frame of the mRNA, and the conserved stem-loop structure in 3' untranslated regions functions as the determinant of Sec incorporation instead of termination of translation. The efficiency of Sec incorporation in Sec-containing enzymes in physiological or selenium (Se)-deficient condition remains unclear. To clarify this, we have developed monoclonal antibodies to human TR, and established a sandwich enzyme-linked immunosorbent assay to determine TR protein content. We observed that the specific activity of cytosolic TR in NCI-H441 cells increased with increasing concentrations of Se in a serum-free medium. The specific activity of TR purified from each cytosol was essentially equal to the calculated specific activity of each cytosolic TR. The Se content of TR increased with increasing concentration of Se in the medium, from 0.32 mol/mol of TR subunit (no SE) to 0.98 mol/mol of TR subunit (500 nM Se), and was directly correlated with the specific activity of TR. When calculated from the cytosolic TR specific activity of human peripheral mononuclear cell, the theoretical efficiency of Sec incorporation in physiological conditions is assumed to be 87%. PMID- 11213470 TI - Immunohistochemical localization of thioredoxin and glutaredoxin in mouse embryos and fetuses. AB - Although oxygen is essential for promoting energy metabolism and for enhancing cell proliferation, early mouse embryos are very sensitive to high oxygen concentration. Because the tissue-specificity and sequential changes of the expression of antioxidative enzymes in rodent embryos have not been investigated systematically, we examined the ontogenesis of thioredoxin (TRX) and glutaredoxin (GRX) in mouse embryos and fetuses by using immunohistochemical methods. These compounds were found to be localized in most tissues examined, with some tissue specificity and temporal sequence. In many tissues, both TRX and GRX began to be expressed at embryonic day 11 (E11) or E13 and appeared to increase later in development, but the heart and great vessels of E8.5 embryos were already positive for their immunoreactivity. The stage at which the antioxidative enzymes begin to be expressed seems to coincide with the stage at which rodent embryos acquire the capacity of aerobic energy metabolism. Although TRX and GRX were co localized in many tissues and showed similar sequential changes of expression, their expression patterns were different in the fetal cartilage, suggesting that they may play different roles in endochondral ossification. Their immunoreactivity was not homogeneous in the liver and the epithelium of uriniferous tubules, probably because their expression is associated with the proliferating and metabolic activities of the cell, as suggested by previous investigators. These results suggest that TRX and GRX play some tissue-specific roles in mammalian morphogenesis as well as general roles as antioxidant enzymes. PMID- 11213471 TI - Molecular cloning and expression of human xCT, the light chain of amino acid transport system xc-. AB - Transport of system xc- is an exchange agency with high specificity for anionic form of cystine and glutamate. The protein mediating this transport is a disulfide-linked heterodimer of a light chain named xCT and a heavy chain previously known as 4F2hc. We have isolated two cDNAs encoding xCT from the human cDNA library. One clone coded for a protein of 501 amino acids with 12 putative transmembrane domains. When functionally expressed in Xenopus oocytes together with the human 4F2hc, human xCT induced the transport activity whose characteristics are similar to those of system xc-. Another clone seemed to contain a partial human xCT and a long 3' untranslated region. The human xCT gene was localized at chromosome 4q28-31. Analysis of the 5'-flanking region of the human xCT gene revealed several sites for potentially binding of transcriptional factors, including NF-E2 and AP-1. Transport of cystine via system xc- has been known as a regulatory factor for the intracellular glutathione level, and its transport activity is induced in response to the oxygen tension in culture. Northern blot analysis demonstrated that the expression of both xCT and 4F2hc was significantly enhanced by oxygen. The results suggest that oxygen regulates the activity of system xc- by modulating the expression of both xCT and 4F2hc mRNAs. PMID- 11213472 TI - Nitric oxide induces a decrease in the mitochondrial membrane potential of peripheral blood lymphocytes, especially in natural killer cells. AB - Increased levels of nitric oxide (NO) at an inflammatory site may affect the biological activity of lymphoid cells. To investigate the effects of NO on the immune system, we measured the mitochondrial membrane potential (delta psi m) of the peripheral blood lymphocytes (PBL) cultured with a chemical NO donor. PBL from healthy volunteers were cultured with NOC18, a NO-generating compound, at various concentrations. The delta psi m of the PBL was measured by flow-cytometry using 3,3-dihexyloxacarbocyanine iodide (DiOC6(3)). NOC18 induced a decrease in the delta psi m of the PBL in a dose-dependent fashion, induced an increase in the levels of reactive oxygen species (ROS), and caused these cells to undergo apoptosis. Dual-color staining of the delta psi m and lymphocyte surface markers demonstrated that CD3-CD56+ natural killer (NK) cells were responsive to NO. Trolox, a vitamin E analog, partially reversed the NO-induced decrease in the delta psi m of the PBL. We showed that the delta psi m of peripheral NK cells were decreased by NO, which suggests that abundant NO at an inflammatory site may impair NK cell function. PMID- 11213473 TI - Serum 4-hydroxy-2-nonenal-modified albumin is elevated in patients with type 2 diabetes mellitus. AB - 4-Hydroxy-2-nonenal (HNE) is one of the major lipid peroxidation products with cytotoxic and mutagenic activity. It further reacts with protein residues such as histidine to generate stable Michael adducts. To evaluate the status of oxidative stress in the serum of type 2 diabetes mellitus, we constructed a sandwich enzyme linked immunosorbent assay to measure serum HNE-modified albumin by the use of a specific monoclonal antibody (HNEJ-2) against HNE-histidine adducts as well as an antibody against human serum albumin. Serum of type 2 diabetes outpatients revealed significantly higher levels of HNE-modified albumin (736.1 +/- 34.2 pmol/ml, n = 54) than the matched nondiabetics (611.4 +/- 39.1 pmol/ml, n = 30; means +/- SEM; p = 0.018). However, no significant correlation was observed in diabetic outpatients between the levels of HNE-modified albumin and clinical parameters such as fasted blood glucose, HbA1c, diabetes duration, or complications. Our data demonstrated the increased formation of serum HNE modified albumin in type 2 diabetic outpatients in the milieu between liver and vascular lumina, indicating the presence of oxidative stress. PMID- 11213474 TI - Thioredoxin levels in the sera of untreated viral hepatitis patients and those treated with glycyrrhizin or ursodeoxycholic acid. AB - Thioredoxin (TRX), a thiol-containing protein, is induced by various oxidative stresses. Serum TRX levels were measured with a sandwich enzyme-linked immunosorbent assay kit in 210 hepatitis C virus (HCV)-infected patients, 39 hepatitis B virus (HBV)-infected patients, and 17 healthy volunteers. The effects of hepatoprotective drugs on TRX levels were also examined. The median TRX levels were significantly higher in HCV-infected patients than in controls (34.2 vs. 23.5 ng/ml, respectively; p < 0.005), but were not elevated in HBV-infected patients (26.7 ng/ml). The TRX levels were significantly correlated with serum lipid peroxide levels and indocyanine green exclusion test values, and were markedly decreased following treatment with Stronger Neo-Minophagen C or ursodeoxycholic acid. In conclusion serum TRX levels, a marker of oxidative stress, were higher in patients with HCV infection than those with HBV infection and healthy controls. The therapeutic efficacy of hepatoprotective drugs may be connected with the decrease in oxidative stress in hepatitis patients. PMID- 11213475 TI - Secretion of thioredoxin enhances cellular resistance to cis diamminedichloroplatinum (II). AB - Thioredoxin (TRX) is a redox-active protein induced by a variety of stress and secreted from cells. Collecting evidence revealed that extracellular TRX shows cytokine- and chemokine-like activities. In the present study, we studied the role of secreted TRX on cellular resistance to cis-diamminedichloroplatinum (II) (CDDP). The CDDP-resistant variants of HeLa cells not only have enhanced expression of intracellular TRX, but also show increased secretion of TRX into the culture medium, compared to the parental cells. The CDDP-resistant cells also exhibit an enhanced L-cystine uptake capability, which results in a significant increase in the intracellular sulfhydryl content, including glutathione (GSH). Exogenous administration of recombinant TRX (rTRX) increases cellular resistance to CDDP and augments the L-cystine uptake in the parental HeLa cells. Moreover, depletion of L-cystine from the culture medium or combined treatment with L cystine uptake inhibitors increases cellular sensitivity to CDDP in the CDDP resistant cells. These findings suggest that secreted TRX may play an important role in the acquisition of cellular CDDP resistance through enhancement of the L cystine uptake activity, and that the L-cystine transport system, as well as the TRX system, may be a novel therapeutic target in CDDP-resistant cancer cells. PMID- 11213476 TI - Thioredoxin blood level increases after severe burn injury. AB - We have investigated the thioredoxin (TRX) levels in severely burned patients and the possible origin of TRX, based on the recent understanding that TRX is a potent antioxidant with cytoprotective functions. Serum and plasma samples from burns patients and healthy blood donors were collected during the first 10 post burn days and analyzed in a sandwich TRX enzyme-linked immunosorbent assay (ELISA). The TRX levels found were correlated to a panel of blood tests. The presence of TRX in platelets was investigated by immunoelectron microscopy and Western blotting. TRX serum levels of the severely burned patients showed a significant increase, with a mean serum TRX concentration on the day of injury of 76.5 +/- 19.5 ng/ml (mean +/- SD) and on post-burn day one 122.6 +/- 66.9 ng/ml, compared to control blood donor levels of 22.7 +/- 12.2 ng/ml (p = 0.0041 and 0.0117, respectively). A second peak of increase was found on post-burn days 7 to 9 with a four- to five-fold rise in concentration compared to controls. TRX elevation correlated well with increased platelet (p = 0.007) and leukocyte counts (p = 0.002). We also demonstrated by immunoelectron microscopy and Western blotting the presence of TRX in platelets. In conclusion, our demonstration of TRX release in burn injuries indicates that the TRX system is involved in a rapid antioxidant defense, coagulation processes, cell growth, and control of the extracellular peroxide tone intimately linked to cytoprotection and wound healing in burns. One of the cell types that delivers TRX promptly and efficiently into the blood may be the platelet. PMID- 11213477 TI - Secretion of 10-kDa and 12-kDa thioredoxin species from blood monocytes and transformed leukocytes. AB - Thioredoxins (TRX) are ubiquitous, small redox-active proteins with multiple functions, including antioxidant, cytoprotective, and chemoattractant activities. In addition to a 12-kDa intracellular form, extracellular 10-kDa and 12-kDa TRX have been defined. The biological activities of the 10-kDa TRX were previously measured as eosinophil cytotoxicity enhancing activity or B-cell stimulatory activity. Cytotrophoblastic cell lines also release a 10-kDa TRX form. To study the biological role of 10-kDa TRX, we established two highly sensitive enzyme linked immuno-spot assays (ELISPOT), which detect secreted truncated 10-kDa and full-length 12-kDa TRX at the single cell level. TRX secretion was investigated in several cell lines including the T-helper cell hybridoma MP6, the Jurkat T cell leukemia, the U-937 myelomonocytic leukemia, and the 3B6, EBV-transformed, lymphoblastoid B-cell line. The highest number of secreting cells was found in 3B6 cultures, median = 34 (quartiles, 27-39) per well (10(5) cells). Peripheral blood monocytes isolated from healthy donors secreted significantly more TRX after stimulation with ionomycin, phorbol myristate acetate (PMA), fMLP, and lipopolysaccharide (LPS), compared to unstimulated cells. Oxidative stress induced by thioloxidant diamide also induced the secretion of both truncated and full-length TRX measured in ELISPOT (p = 0.047 and p = 0.031, respectively). The biological activity of the truncated and full-length forms was tested in a cell migration assay. Truncated TRX was devoid of protein disulfide reductase activity, but retained strong chemoattractant activity for human monocytes, in the same range as full-length TRX, as previously reported (Bertini et al., 1999). PMID- 11213478 TI - Enhanced invasion of Tax-expressing fibroblasts into the basement membrane is repressed by phosphorylated ascorbate with simultaneous decreases in intracellular oxidative stress and NF-kappa B activation. AB - Invasion of rat fibroblastic cells Rat-1 through Matrigel was shown to be promoted by transfection with tax gene of human T-cell leukemia virus type 1. We found that an oxidation-resistant type of vitamin C (Asc), Asc-2-O-phosphate (Asc2P), inhibited the invasion of the tax-transfected Rat-1 cells (W4 cells). Intracellular Asc (Ascin), after enzymatic dephosphorylation of administered Asc2P, was more abundant in W4 cells than in Rat-1 cells, and the ratio of dehydroascorbic acid versus Asc was increased in W4 cells but scarcely in Rat-1 cells, according to the enhanced level of intracellular reactive oxygen species (ROSin) in W4 cells. Asc2P notably repressed the increases in both ROSin and secretion of matrix metalloproteases (MMPs), but did not affect Tax protein expression in tax-transfectants. NF-kappa B activation, as evidenced by its translocation to the nucleus in W4 cells, was also repressed by Asc2P. Thus, the tax-promoted invasion together with the enhanced production of MMPs occurred with NF-kappa B activation and the increase in ROSin, both of which were effectively reduced by Asc2P. These findings indicate the therapeutic efficacy of Ascin enriching agents for the prevention against tumor invasion in which ROSin plays a major role. PMID- 11213479 TI - Role for copper in transient oxidation and nuclear translocation of MTF-1, but not of NF-kappa B, by the heme-hemopexin transport system. AB - Heme-hemopexin (2-10 microM) is used as a model for intravenous heme released in trauma, stroke, and ischemia-reperfusion. A transient increase in cellular protein oxidation occurs during receptor-mediated heme transport from hemopexin which is inhibited by the nonpermeable Cu(I) chelator, bathocuproinedisulfonate. Thus, participation of surface redox process involving Cu(I) generation are proposed to be linked to the induction of the protective proteins heme oxygenase 1 (HO-1) and metallothionein-1 (MT-1) by heme-hemopexin. The region (-153 to -42) in the proximal promoter of the mouse MT-1 gene responds to heme- and CoPP hemopexin in transient transfection assays and contains metal-responsive elements for MTF-1 and an antioxidant-responsive element (ARE) overlapping a GC-rich E-box to which USF-1 and -2 bind. No decreases in DNA binding of the diamide-oxidation sensitive USF-1 and -2 occur upon exposure of cells to heme-hemopexin. MTF-1 and the ARE-binding proteins are relatively resistant to diamide oxidation and are induced approximately eight- and two-fold, respectively, by heme-hemopexin. BCDS prevents the nuclear translocation of MTF-1 by both heme- and CoPP-hemopexin complexes as well as MT-1 mRNA induction by CoPP-hemopexin. Thus, copper is needed for the surface oxidation events and yet the nuclear translocation of MTF 1 in response to hemopexin occurs via copper, probably Cu(I),-dependent signaling cascades from the hemopexin receptor rather than the oxidation per se. PMID- 11213480 TI - Cell-surface events for metallothionein-1 and heme oxygenase-1 regulation by the hemopexin-heme transport system. AB - A model has been developed for the hemopexin receptor-mediated heme transport system based on iron uptake in yeast. Two steps are required: reduction followed by oxidation by a multi-copper-oxidase. Furthermore, in the hemopexin system, the surface redox events have been linked with gene regulation. The impermeable Cu(I) chelator bathocuproinedisulfonate (BCDS) is shown here to abrogate heme oxygenase 1 (HO-1) mRNA induction by heme-hemopexin. A role for Cu(I) in the regulation of HO-1 and MT-1 (Sung et al., 1999) by hemopexin supports the participation of electron transport processes at the cell surface as does competition by the reductase activator, ferric citrate, which inhibits the induction of MT-1 and HO 1 mRNA by heme-hemopexin. There is a key role for the hemopexin receptor because neither ferric citrate nor iron-transferrin alone regulates MT-1 or HO-1. Cell surface copper is the first molecule to link the concomitant regulation of HO-1 and MT-1 by the hemopexin receptor. In addition, cytochrome b5 and cytochrome b5 reductase are implicated here in the response of cells to heme-hemopexin. Reduction of one or more electron donors of the reductase and oxidation of the electron acceptor, b5 heme, leads to gene regulation, but only when heme hemopexin is bound to its receptor. Protein kinase cascades, including JNK, are activated by the hemopexin receptor itself upon ligand binding but are modulated by a Cu(I)-dependent process likely to be heme uptake. PMID- 11213482 TI - Evidence for a NADH/NADPH oxidase in human umbilical vein endothelial cells using electron spin resonance. AB - A growing body of evidence has suggested that a membrane-bound NADH/NADPH oxidase is the predominant source of reactive oxygen species (ROS) in vascular cells. Prior studies have used indirect assessments of superoxide including lucigenin enhanced chemiluminescence, cytochrome c, and fluorescent dye techniques. The present study was performed to determine if NADH/NADPH oxidase function could be detected human endothelial cells using electron spin resonance. Human umbilical vein endothelial cells (HUVEC) were homogenized and fractionated into cytosolic and membrane components. Cell fractions were incubated in buffer containing either NADH or NADPH (100 microM for each) and the spin trap 5 (diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide (DEPMPO). EPR signals were obtained in a Bruker EMX spectrometer. Cytoplasmic fractions were devoid of activity. In contrast, incubation of membrane fractions with NADH produced a signal with a total peak intensity of 1,038 +/- 64, which was significantly greater than that observed with NADPH (540 +/- 101). The signal was completely inhibited by either manganese superoxide dismutase (MnSOD, 100 U/ml) or the flavoprotein inhibitor diphenylene iodinium (DPI, 100 microM). Rotenone (100 microM) did not significantly alter the signal intensity, (833 +/- 88). These data demonstrate direct evidence for a functional NADH/NADPH oxidase in human endothelial cells and show that electron spin resonance is a useful tool for study of this enzyme system. PMID- 11213481 TI - Glutathione-dependent regulation of nitric oxide production in isolated rat hepatocyte suspensions. AB - Freshly isolated suspensions of rat parenchymal liver cells (hepatocytes) spontaneously produce large amounts of nitrite following collagenase isolation. Our previous studies indicate that nitrite production is associated with the expression of inducible nitric oxide synthase (iNOS) and reflects NO production. Depletion of glutathione (GSH) with diethylmaleate (DEM) inhibited nitrite production, and this inhibition was time-dependent. DEM was more effective in blocking nitrite production if it was added within the first 1 hr of the start of the incubation. The reducing agent dithiothreitol (DTT) and the alkylating agent ethyl methanesulfonate (EMS) also inhibited hepatocyte nitrite production, and this inhibition was also greatest if they were added within 1 hr of initiating the incubation. However, EMS added at 3 hr still reduced 6-hr nitrite production by about 70%. This reduction in nitrite production by EMS added at 3 hr may be due to the direct modification of thiol groups on the iNOS protein because we have determined that iNOS activity is inhibited by the sulfhydryl modifying reagent N-ethylmaleimide (NEM). Western blots also indicate that the iNOS protein is expressed when EMS is added at 3 hr. The addition of DEM, DTT, or EMS at 0 time greatly reduced the levels of cellular iNOS mRNA relative to controls as determined by quantitative RT-PCR. Based on our results with mRNA levels, both DTT and depletion of cellular GSH appear to inhibit the early signaling events leading to iNOS expression and suggest that the control of iNOS induction in hepatocytes is sensitive to the thiol redox status of the cell. PMID- 11213483 TI - Anethole dithiolethione regulates oxidant-induced tyrosine kinase activation in endothelial cells. AB - Interaction between neutrophils and endothelial cells is one of the first steps in the functional response of polymorphonuclear neutrophils (PMN), and is necessary for their migration toward damaged tissues. PMN activation, leading to their adhesion to and migration between endothelial cells, is part of a complex phenomenon that can be altered in pathological situations such as the ischemia reperfusion syndrome, in which large numbers of PMN are recruited to the tissue and release reactive oxygen species (ROS) near the vessel wall. ROS have been implicated in the pathogenesis of various inflammatory diseases. The increased adhesion of PMN to ROS-stimulated endothelial cells involves an increase in tyrosine phosphorylation of a tyrosine kinase focal adhesion kinase (p125FAK) and several cytoskeleton proteins, including paxillin and p130 cas. We examined the role of glutathione (GSH) in the regulation of this adhesion phenomenon and in the increased tyrosine phosphorylation induced by ROS. For this purpose we used anethole dithiolthione (ADT), which increases the glutathione synthesis by activating gamma-glutamyl-cysteine synthetase. We found that ADT reduced both PMN adhesion to ROS-stimulated human umbilical vein endothelial cells (HUVEC) and tyrosine phosphorylation of p125FAK and paxillin. ADT increased redox status by increasing intracellular GSH content in oxidized cells. These results show that GSH can reverse the effect of oxidation on tyrosine kinase activation and phosphorylation, and thus plays an important role in cell signaling. They also confirm the antioxidant activity of ADT. PMID- 11213484 TI - The mitochondrial thioredoxin system. AB - Eukaryotic organisms from yeast to human possess a mitochondrial thioredoxin system composed of thioredoxin and thioredoxin reductase, similar to the cytosolic thioredoxin system that exists in the same cells. Yeast and mammalian mitochondrial thioredoxins are monomers of approximately 12 kDa and contain the typical conserved active site WCGPC. However, there are important differences between yeast and mammalian mitochondrial thioredoxin reductases that resemble the differences between their cytosolic counterparts. Mammalian mitochondrial thioredoxin reductase is a selenoprotein that forms a homodimer of 55 kDa/subunit; while yeast mitochondrial thioredoxin reductase is a homodimer of 37 kDa/subunit and does not contain selenocysteine. A function of the mitochondrial thioredoxin system is as electron donor for a mitochondrial peroxiredoxin, an enzyme that detoxifies the hydrogen peroxide generated by the mitochondrial metabolism. Experiments with yeast mutants lacking both the mitochondrial thioredoxin system as well as the mitochondrial peroxiredoxin system suggest an important role for mitochondrial thioredoxin, thioredoxin reductase, and peroxiredoxin in the protection against oxidative stress. PMID- 11213485 TI - Antioxidant function of thioredoxin and glutaredoxin systems. AB - Selenium is an essential trace element with known antioxidant properties. Cytosolic thioredoxin reductase from mammalian cells is a dimeric flavin enzyme comprising a glutathione reductase-like equivalent elongated with 16 residues including the conserved carboxy-terminal sequence, Gly-Cys-SeCys-Gly, where SeCys is selenocysteine. Replacement of the SeCys residue by Cys in rat cytosolic thioredoxin reductase using site-directed mutagenesis and expression in Escherichia coli resulted in a functional mutant enzyme having about one percent activity with thioredoxin as a substrate through a major loss of Kcat and a shift in the pH optimum from 7 to 9. The truncated enzyme expected in selenium deficiency by the UGA mRNA codon for SeCys acting as a stop codon was also expressed. This enzyme lacking the carboxy-terminal SeCys-Gly dipeptide contained FAD but was inactive because the SeCys selenol is in the active site. These results show that selenium is essential for the activity of thioredoxin reductase, explaining why this trace element is required for cell proliferation by effects on thioredoxin-dependent control of the intracellular redox state, ribonucleotide reductase production of deoxyribonucleotides, or activation of transcription factors. The selenazol drug ebselen (2-phenyl-1,2 benzisoselenazol 3 (2H)-one) is a known glutathione (GSH) peroxidase mimic with antioxidant properties. The hydrogen peroxide reductase activity of human thioredoxin reductase was stimulated 15-fold by 2 microM ebselen. Glutaredoxins protect against oxidative stress by catalyzing reduction of protein mixed disulfides with GSH. The mechanism of glutaredoxins as efficient general GSH-mixed disulfide oxidoreductases may protect proteins from inactivation as well as play a major role in general redox signaling. PMID- 11213486 TI - Vitamin E and leukocyte-endothelial cell interactions. AB - Leukocyte-endothelial cell interactions are mediated by adhesion molecules, expression of which is modulated by cytokines and chemical mediators in the early phase of inflammatory and immunologic reactions, including the development of atherosclerosis. Vitamin E is a lipid-soluble antioxidant that is present in all cell membranes at a low concentration and is reported to be an anti-atherogenic agent. Recently, it was reported that vitamin E inhibits the activation of protein kinase C and nuclear factor-kappa B (NF-kappa B). We demonstrated that vitamin E can prevent leukocyte-endothelial cell adhesion by inhibiting signal transduction involved in the surface expression of adhesion molecules by leukocytes and endothelial cells. These results suggest that vitamin E may have a protective effect against the progression of inflammation and atherosclerosis. PMID- 11213487 TI - Molecular views of redox regulation: three-dimensional structures of redox regulatory proteins and protein complexes. AB - The last decade has witnessed the explosion of research on redox-controlled cellular and biochemical processes. Whereas the vast majority of these studies have centered on clinical, genetic, and biochemical aspects of redox signaling and regulation inside and outside the cell, a significant number of nuclear magnetic resonance (NMR) and crystallographic studies have been undertaken to obtain an atomic-level understanding of the mechanisms of the redox regulation. This review highlights the recent progress of three-dimensional structure determination of key proteins and protein complexes involved in redox regulation. An increased list of such class of protein structures and their complexes with ligands will provide invaluable insight into the molecular basis of redox regulatory processes and may be useful for the future development of therapeutic agents for redox-related diseases. PMID- 11213489 TI - Redox control of protein degradation. AB - This review summarizes evidence that most of cell protein degradation is maintained by pathways transferring energy from glucose to reduction of enzymic and nonenzymic proteins (redox-responsive). In contrast, a major subcomponent of proteolysis is simultaneously independent of the cell redox network (redox unresponsive). Thus far, direct and indirect redox-responsive proteolytic effector mechanisms characterized by various investigators include: several classes of proteases, some peptide protease inhibitors, substrate conjugation systems, substrate redox and folding status, cytoskeletal-membrane kinesis, metal homeostasis, and others. The present focus involves redox control of sulfhydryl proteases and proteolytic pathways of mammalian muscle; however, other mechanisms, cell types, and species are also surveyed. The diversity of redox responsive catabolic mechanisms reveals that the machinery of protein turnover evolved with fundamental dependencies upon the cell redox network, as observed in many species. The net redox status of a reversible proteolytic effector mechanism represents the balance between combined oxidative inactivating influences versus reductive activating influences. Similar to other proteins, redox-responsive proteolytic effectors appear to be oxidized by mixed disulfide formation, nitrosation, reactive oxygen species, and associations or reactions with metal ions and various pro-oxidative metabolites. Systems reducing the proteolytic machinery include major redox enzyme chains, such as thioredoxins or glutaredoxins, and perhaps various reductive metabolites, including glutathione and dihydrolipoic acid. Much of mammalian intracellular protein degradation is reversibly responsive to noninjurious experimental intervention in the reductive energy supply-demand balance. Proteolysis is reversibly inhibited by diamide or dehydroascorbic acid; and such antiproteolytic actions are strongly dependent on the cell glucose supply. However, gross redox-responsive proteolysis is not accompanied by ATP depletion or vice versa. Redox-responsive proteolysis includes Golgi-endoplasmic reticulum degradation, lysosomal degradation, and some amount of extravesicular degradation, all comprising more than half of total cell proteolysis. Speculatively, redox-dependent proteolysis exhibits features expected of a controlling influence coordinating distinct proteolytic processes under some intracellular conditions. PMID- 11213490 TI - Detection and imaging of endogenously produced nitric oxide with electron paramagnetic resonance spectroscopy. AB - Nitric oxide (NO) represents a new paradigm for second messengers in regulation. Despite the numerous physiological and pathophysiological functions of NO, its importance as an endogenous second messenger and a cytostatic and/or cytotoxic agent was unknown until 1987. Recent developments in detection methods for endogenous NO produced directly or indirectly from NO synthases (NOSs) have enabled major advances in our understanding of the role of NO in biological systems. The spin-trapping technique combined with electron paramagnetic resonance (EPR) spectroscopy is a method for analyzing NO production directly both in vivo and in vitro. Iron complexes with dithiocarbamate derivatives are noteworthy among the spin-trapping reagents for NO because NO has a high affinity for iron complexes. The resultant stable nitrosyl iron complexes exhibit an intense three-line signal at room temperature and an axial signal at low temperature. Besides the facility and wide applicability of this method, its outstanding feature is that noninvasive in vivo measurements are available by using a low-frequency EPR spectrometer. In this article, we review on previous and recent developments of in vitro, in vivo, and ex vivo EPR detection and imaging of endogenously produced NO. PMID- 11213488 TI - Molecular mechanism of activation and superactivation of Ret tyrosine kinases by ultraviolet light irradiation. AB - The catalytic activities of Ret tyrosine kinases as the products of oncogene RET with multiple endocrine neoplasia type 2A (Ret-MEN2A) or 2B (Ret-MEN2B) mutations and the hybrid gene from c-RET and RFP (Rfp-Ret) were higher than those of c-Ret. We demonstrated that ultraviolet light (UV) irradiation induced activation of c Ret and superactivation of genetically mutated, and thereby constitutively activated, Ret-MEN2A, Ret-MEN2B, and Rfp-Ret. We found that small proportions of c-Ret and Ret-MEN2B and a large proportion of MEN2A were dimerized due to disulfide bonds and that high kinase activity resided in these fractions. The UV induced activation of c-Ret and superactivation of Ret-MEN2A and Ret-MEN2B were then shown to be closely associated with promotion of the disulfide bond-mediated dimerization of the Ret proteins. Furthermore, we showed that a large proportion of Rfp-Ret was dimerized or polymerized and that almost all kinase activities resided in the highly polymerized but not dimerized fraction. The UV-induced superactivation of Rfp-Ret was also found to be closely associated with promotion of polymerization but not with dimerization of Rfp-Ret. Further experiments revealed that UV induced intracellular dimerization and activation of the extracellular domain-deleted mutant Ret (Ret-PTC-1). Most importantly, the levels of basal kinase activity and dimerization of Ret-TPC-1-C376A, in which cysteine 376 in the tyrosine kinase domain of Ret-TPC-1 was replaced with alanine, were low and were not increased by UV irradiation. These results suggest that the cysteine at this position works as the primary target of dimerization of Ret proteins inside the cell for both the maintenance of the basal kinase activity and its promotion by UV, possibly in co-operation with the cysteine(s) in the extracellular domain of Ret-MEN2A and Rfp-Ret, which is the target of dimerization and polymerization outside the cell. The potential biological significance of the UV-mediated superactivation of mutant Ret through the newly proposed mechanism in oncogenesis is discussed. PMID- 11213491 TI - Oxidants and antioxidants in breast cancer. AB - Although a number of risk factors have been identified for breast cancer, mechanisms by which they increase risk of the disease are not clear. Breast cancer etiology could, in part, be related to oxidative stress. Recognized risk factors for breast cancer include a family history of the disease. BRCA1 is needed for post-transcriptional repair of oxidative damage, indicating that oxidative stress may be an important risk factor for women with a family history of the disease. Reproductive and hormonal factors that result in greater exposure to circulating estrogens also increase risk, and steroid hormones are metabolized to reactive quinones and hydroquinones, which can directly damage DNA. Alcohol consumption is associated with increased risk, and the metabolism of alcohol results in production of DNA-damaging reactive oxygen species (ROS). Finally, the inverse relationship noted with consumption of fruits and vegetables could be related to their being a source of antioxidant vitamins. Endogenous factors may play an equally important role in the effects of oxidative stress on breast carcinogenesis. Genetic variability in enzymes that result in increased production of ROS and those that protect the cell from oxidative stress could also have an impact for risk of the disease. In this review, a rationale is given for linking breast cancer risk factors to oxidative stress. The possible role of genetic polymorphisms in a number of enzymes that may be important in affecting levels of ROS to which the cell is exposed, as well as those that protect the cell from oxidative stress, is discussed. PMID- 11213492 TI - Redox control of vascular nitric oxide bioavailability. AB - NO is an important component of vascular homeostasis and abnormal NO bioactivity has been implicated in number of disease states with important public health implications. One clear mechanism of impaired NO bioactivity and vascular disease is excess vascular oxidative stress. There is now a wealth of developing data that manipulation of vascular antioxidant stress is the considerable influence of the biologic activity of endothelium-derived NO. It remains to be seen if this influence can be exploited in a manner that truly alters the course of human disease. PMID- 11213493 TI - Antioxidants and redox signaling: Internet resources. PMID- 11213494 TI - Hospital not responsible for physician's death. Campo v. St. Luke's Hospital. PMID- 11213495 TI - Home health nurses may be paid on a "per visit" basis and still be exempt. Fazekas v. the Cleveland Clinic Foundation Health Care Ventures, Inc. PMID- 11213496 TI - Immunity provisions: they must be read carefully. Ironside v. Simi Valley Hospital. PMID- 11213497 TI - Usefulness of intraoperative cytology for the diagnosis of primary pancreatic lymphoma. PMID- 11213498 TI - Adult rhabdomyosarcoma with skin metastases: diagnosis by fine needle aspiration biopsy. PMID- 11213499 TI - Characterizing subpopulations of neoplastic cells in serous effusions. The role of immunocytochemistry. AB - OBJECTIVE: To analyze the role of immunochemistry in serous effusions. STUDY DESIGN: We analyzed cell blocks of 18 pleural and 18 peritoneal effusions diagnosed as malignant (18), benign (14) and suspicious (4). They were immunostained by the avidin-biotin complex method with a panel of four monoclonal antibodies--CEA, Ber-EP4, LeuM1 (CD15) and p53--and, for lectins (Ulex europaeus) UEA-l, ConA and ConBr. RESULTS: Seventeen of the 18 cases of adenocarcinoma were positive for CEA (95%), 12 (66.6%) for Ber-EP4, 11 (61%) for CD15 and 11 (61%) for p53. Twelve of the 18 (66.6%) were positive for UEA-1, CEA, Ber-EP4 and CD15. UEA-1 did not react with mesothelial cells. p53 Gave a positive reaction in only one case, reactive mesothelial cells. ConA and ConBr reacted indiscriminately with benign and malignant cells; thus, it was not useful in distinguishing between these cells. CONCLUSION: In this context no antibody used alone is reliable for corroborating a diagnosis, but the selective use of a small panel of three markers (CEA, Ber-EP4 and LeuM1) can be very useful in solving diagnostic difficulties in the cytodiagnosis of serous effusions. PMID- 11213500 TI - Repeat cervical cytology at the time of colposcopy. Is there an added benefit? AB - OBJECTIVE: To determine if repeating the Pap smear (PS) at colposcopy offers added benefit in the detection of cervical squamous intraepithelial lesions (SILs). STUDY DESIGN: Eight hundred fifty-two women were subjects of this study. Patients with cervical SIL were defined as women with SIL on the repeat PS, or SIL on the colposcopic cervical biopsy (bx) or a negative repeat PS and bx but confirmed SIL on both the previous and follow-up PS or bx. The sensitivities of repeat PS and bx in detecting SIL were calculated. The chi 2 test was used to assess statistical significance. The total cost of repeating the PS was calculated by multiplying the total number of patients (852) by the estimated cost of a single PS ($25). RESULTS: The sensitivities of repeat PS, bx and PS/bx combined were .89, .69 and .92 for low grade SIL (LSIL) and .74, .77 and .98 for high grade SIL (HSIL), respectively (P < .0001). Sixteen percent of the HSIL and 28% of the LSIL cases were diagnosed on repeat PS only (negative bx). If repeat PS was omitted, $21,300 would have been saved. PMID- 11213501 TI - Cost analysis of PAPNET-assisted vs. conventional Pap smear evaluation in primary screening of cervical smears. AB - OBJECTIVE: To assess the difference in costs between PAPNET-assisted and conventional microscopy of cervical smears when used as a primary screening tool. STUDY DESIGN: We performed time measurements of the initial screening of smears by four cytotechnologists in one laboratory. Time was measured in 816 conventionally screened smears and in 614 smears with PAPNET-assisted screening. Data were collected on the components of initial screening, clerical activities and other activities in the total work time of cytotechnologists in the routine situation and on resource requirements for both techniques. RESULTS: PAPNET saved an average of 22% on initial screening time per smear. Due to costs of processing and additional equipment, the costs of PAPNET-assisted screening were estimated to be $2.85 (and at least $1.79) higher per smear than conventional microscopy. The difference in costs is sensitive to the rate of time saving, the possibility of saving on quality control procedures and the component of the initial screening time in the total work time of cytotechnologists. CONCLUSION: Although PAPNET is time saving as compared with conventional microscopy, the associated reduction in personnel costs is outweighed by the costs of scanning the slides and additional equipment. This conclusion holds under a variety of assumptions. Using PAPNET instead of conventional microscopy as a primary screening tool will make cervical cancer screening less cost-effective unless the costs of PAPNET are considerably reduced and its sensitivity and/or specificity are considerably improved. PMID- 11213502 TI - Molecular biomarker-based screening for early detection of cervical cancer. AB - OBJECTIVE: To evaluate the effectiveness of a molecular biomarker-based screening method for early detection of cervical cancer. STUDY DESIGN: Fluorescent immunochemical labeling was used to classify cervical cytology specimens as probably normal or probably abnormal. These specimens were then Papanicolaou stained and evaluated twice by a cytotechnologist and by a pathologist when appropriate. The first evaluation was performed as conventional Pap screening to assign a reference per-specimen diagnosis. The second evaluation assigned a cytologic diagnosis to each cell in the specimen. The fluorescence results were correlated with those from each of the two morphologic evaluations to determine the sensitivity and specificity of the method on a per-specimen and a per-cell basis. Where available, in cases of positive morphologic analysis, biopsy was compared to fluorescence results. RESULTS: The per-specimen sensitivity and specificity were 87.5% and 81.8%, respectively, when using atypical squamous cells of undetermined significance and "above" as the decision threshold. For the same specimens evaluated on a cell-by-cell basis, the corresponding sensitivity and specificity were 71.4% and 66.3% when the same threshold was used. The per specimen sensitivity for high grade squamous intraepithelial lesions was 100% under these conditions. CONCLUSION: This method appears to be a robust and reliable means of detecting cervical dysplasia and is now being evaluated in additional clinical studies. PMID- 11213503 TI - Nuclear grooves. How specific are they? AB - OBJECTIVE: To study the significance of nuclear grooves in thyroid and extrathyroid benign and malignant lesions. STUDY DESIGN: In this retrospective study, 26 cases were selected randomly, consisting of papillary carcinoma of the thyroid (7), papillary adenocarcinoma (9), normal cervical smear (5) and benign bronchioalveolar lavage (BAL) (5). In all cases hematoxylin and eosin- and Papanicolaou-stained smears were studied for nuclear grooves. RESULTS: Except for one case of papillary adenocarcinoma, nuclear grooves were discernible in all cases. The highest number of nuclear grooves was seen in normal cervical smears, followed by papillary carcinoma of the thyroid, papillary adenocarcinoma and BAL smears. CONCLUSION: The number of grooves did not correlate with either benign or malignant conditions. These findings cast serious doubt about the diagnostic significance of nuclear grooves. Probably nuclear grooves are nonspecific findings and should be considered only in association with other diagnostic features. PMID- 11213504 TI - Benign cellular changes in Pap smears. Causes and significance. AB - OBJECTIVE: We reviewed consecutive cases classified as benign cellular changes (BCC) over a four-month period. STUDY DESIGN: Cases classified as BCC were retrieved from the cytology files. A search was carried out to identify the previous Pap smears and concomitant cervical biopsies. RESULTS: One thousand one hundred three cases (23% of our gynecologic smears) were classified as BCC. Ninety-two patients (8.3%) underwent concurrent cervical biopsies. Specific infections accounted for 8% of BCC cases; reactive changes accounted for 92%. Of the biopsy specimens, 8.3% had no significant pathologic change. The most common biopsy diagnoses were cervicitis (31.5%), immature squamous metaplasia (16.3%) and reserve cell hyperplasia (10.8%). Miscellaneous benign diagnoses accounted for 21.7%. Cervical intraepithelial neoplasia (CIN) 1/human papillomavirus (HPV) was present in 14% of cases. All patients with biopsy diagnoses of CIN 1 had at least two previous abnormal Pap smears. Previous biopsy reports were available for review in 127 (12%) of the 1,103 patients. Of these 127 cases, 53.5% had a previous diagnosis of CIN/HPV; 9.4% had invasive carcinoma. A benign diagnosis was reported in 36.5%. CONCLUSION: The majority of BCC cases are due to reactive and inflammatory processes. In patients with a previous history of CIN, BCC may be of some significance. In patients with no significant prior cervical abnormalities, a Pap smear classified as BCC represents a reactive process. PMID- 11213505 TI - Cerebrospinal fluid cytologic findings in multiple sclerosis. A comparison between patient subgroups. AB - OBJECTIVE: To compare cytologic findings in cerebrospinal fluid (CSF) in various subgroups of multiple sclerosis (MS) patients. STUDY DESIGN: CSF from 77 patients with clinically definitive or probable MS was examined by means of qualitative cytology. After the cell count was determined in a Fuchs-Rosenthal chamber, slides were prepared by the cytosedimentation method and stained with May Grunwald-Giemsa stain and oil red O and, whenever possible, with Papanicolaou stain and toluidine blue. In addition to the differential cell count, the lymphocyte/monocyte ratio, percentage of activated forms in the lymphocytic and monocytic series, presence and percentage of lymphoplasmacytes and mature plasma cells, presence of lipophages, lymphophages and presence of mitotic figures were evaluated. RESULTS: The following statistically significant differences were found between the various MS subgroups: (1) higher prevalence of mitotic figures in the primary progressive MS subgroup; (2) higher prevalence of foam cells and lymphophages and lower prevalence of CSF pleocytosis in more severely disabled patients; (3) lower cell count, lower prevalence of CSF pleocytosis, lower lymphocyte/monocyte ratio and lower prevalence of lymphoplasmacytes in treated patients; and (4) higher prevalence of mature plasma cells and lipophages in MS patients with disease of longer duration. CONCLUSION: The differences observed in the various MS subgroups may reflect certain aspects of MS pathogenesis. Qualitative CSF cytology may therefore be useful for both clinicians and neuroimmunologists. Qualitative cytology of CSF is an important diagnostic method that should never be omitted from an examination of CSF from patients with MS. PMID- 11213506 TI - Routine air drying of all smears prepared during fine needle aspiration and intraoperative cytology studies. An opportunity to practice a unified protocol offering the flexibility of choosing a variety of staining methods. AB - OBJECTIVE: To evaluate the possibility of routine use of air-dried smears (ADS) instead of wet-fixed smears (WFS). STUDY DESIGN: Intraoperative cytology (IC) smears from 293 specimens and fine needle aspiration cytology (FNAC) smears from 118 cases were studied. Cytomorphology of ADS processed with our protocol for hematoxylin-eosin (HE) and Papanicolaou (PAP) staining after saline rehydration and postfixation in 95% ethanol with 5% acetic acid were compared with respectively stained WFS. Additional ADS were stored up to 72 hours at room temperature prior to HE, PAP and Diff-Quik (DQ) staining to evaluate the effects of postponing rehydration and postfixation. Special stains for fungi were also studied in four cases. RESULTS: ADS were easy to prepare without air-drying artifact in the final HE- and PAP-stained smears. ADS were more cellular than WFS. Erythrocyte interference was frequent in WFS. HE and PAP staining of ADS stored up to 72 hours showed cytomorphology comparable to that of the similarly stained fresh smears. However, DQ staining was better if ADS were processed before 24 hours. ADS stained with special stain for fungi showed good morphology, similar to that in WFS. CONCLUSION: All ADS showed results comparable to or better than WFS. ADS could be stored up to 72 hours before staining with HE and PAP. ADS offers the flexibility of selecting a variety of staining methods and is a practical alternative to WFS. PMID- 11213507 TI - Infantile cartilaginous hamartoma of the rib. A case report. AB - BACKGROUND: Infantile cartilaginous hamartoma of the rib is a rare condition occurring in newborn infants, with an incidence of 1 in 3,000 (0.03%) among primary bone tumor cases. Reports of this condition so far have presented the clinical, radiologic and histopathologic features. To the best of our knowledge, reports of the cytopathologic features have not been documented. In the present case report, clinical, radiologic and cytopathologic features and differential diagnosis are enumerated. CASE: A 1-month-old, male infant presented with a chest wall mass with a clinical diagnosis of osteochondroma. On fine needle aspiration cytology, a diagnosis of infantile cartilaginous hamartoma of the rib was suggested; it was supplemented by the clinical history and radiologic findings. CONCLUSION: Although rare, this condition ought to be kept in mind while dealing with infantile chest wall masses to avoid an erroneous diagnosis of malignancy, owing to its ominous cytopathologic features. PMID- 11213508 TI - Cytologic features of pleural effusion in apocrine sweat gland carcinoma. A case report. AB - BACKGROUND: Carcinoma arising in the apocrine sweat glands is very rare, and there are few reports of the cytologic features. We encountered a case of metastatic apocrine carcinoma in a pleural effusion. CASE: A 46-year-old male had a dark reddish nodule in the right axillary region that was diagnosed as apocrine carcinoma of skin appendage origin. Three years after wide resection and chemotherapy, widespread metastases developed with a massive pleural effusion. Needle aspiration fluid cytology contained clusters of adenocarcinoma. Some tumor cells had abundant cytoplasm or periodic acid-Schiff-positive, coarse granules. Decapitation secretion was occasionally found on the cell surface. Immunohistochemically, the tumor cells were often positive for BRST-2 and BRST-3. CONCLUSION: Cytologic features of metastatic apocrine sweat gland carcinoma show some characteristics of adenocarcinoma. Moreover, its definitive diagnosis in a pleural effusion can be made because of retaining the characteristics of apocrine sweat gland. PMID- 11213509 TI - Paracoccidioides brasiliensis in a postpartum Pap smear. A case report. AB - BACKGROUND: There are several reported cases that describe female genital tract infections with opportunistic fungi, such as Blastomyces dermatitidis, Coccidioides immitis, Aspergillus flavus, Cryptococcus neoformans and Mucor. We describe a case of paracoccidiodomycosis limited to the uterine cervix. To the best of our knowledge, no such case has been described before in the English language literature. CASE: A 27-year-old, healthy female, gravida 3, para 2, abortion 1, presented for a routine gynecologic examination at six weeks' postpartum. Her past medical history was unremarkable. A routine cervical/endocervical smear revealed the presence of multiple fungal forms at different stages of development with a characteristic "pilot's wheel" appearance consistent with Paracoccidioides brasiliensis. Detailed medical examination of the patient did not reveal the presence of the primary infection in any other system. Cultures of the endometrium revealed no growth of the fungal organisms. The patient was asymptomatic, and therefore no therapy was initiated. Repeat Papanicolaou smears were negative for organisms. CONCLUSION: Paracoccidioidomycosis can present as a limited form, involving the cervix only. Identification and recognition of the infection are important in cytopathology. PMID- 11213510 TI - Intraabdominal desmoplastic small cell tumor mimicking adenocarcinoma. A case report. AB - BACKGROUND: Fine needle aspirates and washings from intraabdominal desmoplastic small cell tumors (IADSCTs) are rarely encountered by pathologists. Immunocytochemical examination of histologic material is usually necessary for a definitive diagnosis. CASE: A 23-year-old man presented with abdominal pain, ascites and bilateral pleural effusion. Examination of ascitic fluid suggested adenocarcinoma, but histologic and immunocytochemical examination of surgically resected tissue showed features of an IADSCT. CONCLUSION: This case is a reminder that IADSCT should be included in the differential diagnosis of intraabdominal neoplasms and that its diagnosis in cytologic preparations requires a high index of suspicion. In particular, this case appears to be the first reported example of IADSCT mimicking adenocarcinoma. PMID- 11213511 TI - Fine needle aspiration cytology of soft tissue chondroma. A case report. AB - BACKGROUND: Soft tissue chondroma, though rare, is well known to histopathologists and radiologists. Cytologic features of soft tissue chondroma mimic those of its malignant counterpart to a considerable extent. To our knowledge, this is the first case in which the aspiration cytology of soft tissue chondroma is described as an aid to definitive diagnosis. CASE: A 54-year-old male presented with a 6 x 5-cm swelling on his right forearm that had existed for 20 years. Its extraskeletal location was confirmed. Aspiration cytology showed myxofibrillary material and pleomorphic cells. CONCLUSION: The clinical, radiologic and cytologic triad is important for the correct cytologic diagnosis of soft tissue chondroma despite worrisome cell atypia. PMID- 11213512 TI - Peritoneal effusion in a dog secondary to visceral mast cell tumor. A case report. AB - BACKGROUND: Mast cell tumor, one of the most common skin tumors in dogs, may also be found in visceral sites (mainly spleen and liver). When a visceral mast cell tumor is present, neoplastic mast cells may be found in any effusion secondary to the tumor. Therefore, the diagnosis may be made by cytologic analysis of the effusion. CASE: An 8-year-old, spayed, female Siberian husky presented with a peritoneal effusion secondary to a visceral mast cell tumor. Seven months earlier, the dog had presented with a cutaneous nodule diagnosed as a well differentiated mast cell tumor. The peritoneal fluid was classified as a transudate. Numerous neoplastic mast cells were found in the effusion. Although the mast cell tumor presented with characteristics of the well-differentiated tumor, its biologic behavior was that of a malignant tumor. CONCLUSION: Care should be taken to evaluate the prognosis of mast cell tumors in dogs since their biologic behavior is extremely variable. PMID- 11213513 TI - Fine needle aspiration of gastrointestinal stromal tumors. AB - OBJECTIVE: Gastrointestinal stromal tumors (GISTs) are uncommon mesenchymal tumors of the gastrointestinal tract. Fine needle aspiration (FNA) is one option for diagnosing GISTs before surgery. This study was designed to evaluate the clinical utility of FNA in the diagnosis of GISTs. STUDY DESIGN: FNAs from 19 GISTs originating in the stomach, small bowel and colon obtained from 1988 to 1998 were studied. Immunocytochemistry was performed on 12 cases. The GISTs were classified as benign, borderline and malignant, according to location, size, mitotic activity and clinical outcome. RESULTS: Benign (three) and borderline (five) GISTs were all spindle cell type; malignant GISTs included five spindle cell type and six epithelioid type. Most smears contained abundant cellular material. Benign and borderline GISTs of spindle cell type tended to have cells arranged in tightly cohesive clusters, while malignant GISTs were more likely to exhibit loosely cohesive groups with many single cells, occasional nuclear pleomorphism, hyperchromasia and irregular nuclear contours. Epithelioid-type GISTs mimicked adenocarcinoma. Mitoses were seldom observed in either type. CD117 (KIT protein product) was demonstrated by immunocytochemistry in 9 cases, CD34 in 11, desmin in 3, S-100 protein in 2 and smooth muscle actin in 6 cases. CONCLUSION: FNA can be used to diagnose GISTs as spindle cell and epithelioid types, but cytomorphology alone cannot be used to assess malignant potential. Immunocytochemical staining for CD117 is helpful in confirming the diagnosis. Care must be taken to differentiate epithelioid-type GISTs from adenocarcinoma. PMID- 11213514 TI - Spindle cell lipoma of the oral cavity. Report of a rare intramuscular case with fine needle aspiration findings. AB - BACKGROUND: Spindle cell lipoma (SCL) is a benign neoplasm characterized by a mixture of mature fat, bland spindle cells and wiry collagen in a variably myxoid background. Oral SCLs are rare, and only four cases of intramuscular SCL exist in the literature. We report the first case of intramuscular SCL of the oral cavity with fine needle aspiration (FNA) findings. CASE: A 61-year-old woman presented with a 3-cm mass in the right gingivobuccal sulcus. Papanicolaoustained FNA smears were hypocellular and contained loose collections of spindle cells in a myxoid background, numerous mast cells, rare capillary fragments and portions of skeletal muscle. The spindle cells had mild nuclear enlargement, focal nuclear irregularities, rare intranuclear inclusions and occasional small nucleoli. No lipoblasts or mitoses were identified. There was intermingling of the spindle cells with the skeletal muscle fragments. CONCLUSION: Intraoral SCL is a rare lesion but should be considered in the differential for a benign spindle cell neoplasm in the oral cavity. Clues to diagnosis on cytology include mature fat, bland spindle cells, a myxoid background and mast cells. PMID- 11213516 TI - Adolescent medicine: a resident's perspective. PMID- 11213515 TI - Understanding the adolescent with developmental disabilities. PMID- 11213517 TI - The pediatrician's adolescent children. PMID- 11213518 TI - The resilient adolescent: implications for the pediatrician. PMID- 11213519 TI - Treating the adolescent who might be "out of control". PMID- 11213520 TI - How many more Columbines? What can pediatricians do about school and media violence? PMID- 11213521 TI - Why today's adolescents behave differently from those of earlier generations. PMID- 11213522 TI - Cervicogenic headache (CEH): notes on some burning issues. PMID- 11213523 TI - R3 nociceptive reflex in multiple sclerosis patients with paroxysmal symptoms treated with gabapentin. AB - Gabapentin (GBP) is a new, well-tolerated antiepileptic drug found to be effective for painful paroxysmal symptoms (PS) in multiple sclerosis (MS). The aim of this study was to obtain a neurophysiological evaluation of the effects of GBP on the nociceptive system of MS patients suffering PS. We studied 10 MS patients, 6 males, 4 females (mean age 47.3 years), suffering PS (3 had trigeminal neuralgia, 1 painful tonic spasms and 6 dysesthetic or paresthetic symptoms). Three patients were, at the same time, also being treated with carbamazepine. Pain was evaluated by means of the Visual Faces Scale. R3 nociceptive reflex was recorded after 2 weeks' treatment. R3 thresholds and latencies were evaluated and a statistical analysis was performed. A significant variation was found in R3 thresholds between the values recorded before and during GBP treatment; no significant variation was observed in R3 latencies. PMID- 11213524 TI - Abnormal H-Tfam in a patient harboring a single mtDNA deletion. AB - We report on a patient suffering from a progressive mitochondrial disorder characterized by ocular myopathy, exercise intolerance, and muscle wasting. Morphological examination of muscle biopsy showed increased variability in fiber size and scattered ragged-red fibers. Analysis of muscle mitochondrial DNA by Southern blot and PCR revealed a heteroplasmic single deletion of 4100 base pairs, located between nucleotide positions 8300 and 12,400. Western blot analysis showed high levels of the human mitochondrial transcription factor A (Tfam). Interestingly, we also detected an additional Tfam product, of approximately 22 kDa. This is the first case in which a qualitatively abnormal Tfam has been found to be associated with a mitochondrial disorder in humans. PMID- 11213525 TI - Case-control study on the epidemiology of cluster headache. II: Anthropometric data and personality profile. AB - Several papers have been published on the possible risk factors and conditions associated with CH which may provide clues to its underlying etiopathogenesis, including a typical physical appearance and peculiar psychological characteristics. The aim of the present study was to evaluate the presence of peculiar somatic and psychological features in CH patients by means of a case control study. One hundred and twenty CH patients and as many gender- and age matched controls completed the Minnesota Multiphasic Personality Inventory and underwent 20 cranial and body measurements. The photographs of 71 male subjects (38 cases and 33 controls) were examined by two experienced neurologists who had to decide which subjects were affected by CH. Both cases and controls showed normal personality profiles, without any significant difference emerging between them. None of the head, facial or body measurements differed between cases and controls, except for midface height. The sensitivity and specificity of the patients' pictures for the diagnosis of CH were found by examiner 1 to be 0.71 and 0.67 respectively, and by examiner 2 to be 0.63 and 0.58 respectively. CH patients do not seem to have a peculiar personality profile. While their physiques do not seem to differ substantially from those of the general population, certain skull and/or skin characteristics could lend some patients a typical face appearance. PMID- 11213526 TI - Mechanism of cell death in experimental models of Parkinson's disease. PMID- 11213528 TI - Possible cellular mechanism accounting for the cell type-specific vulnerability in Huntington's disease. PMID- 11213527 TI - Animal models of Huntington's disease: from basic research on neuronal death to assessment of new therapeutic strategies. PMID- 11213529 TI - Animal models of dystonia. PMID- 11213530 TI - Mapping neuronal activity of the basal ganglia in experimental models of Parkinson's disease: contributions of the [14C]2-deoxyglucose method. PMID- 11213531 TI - Risk factors for the development of diabetes. PMID- 11213532 TI - Factors related to the development of diabetes during a 20-year follow-up. A prospective study in a homogeneous group of middle-aged men. AB - BACKGROUND AND AIMS: To investigate factors associated with the development of type 2 diabetes mellitus (DM) during a 20-year follow-up in a homogeneous group of initially healthy middle-aged men with similar socioeconomic status. METHODS AND RESULTS: We studied 1802 executives and businessmen, born 1919-34, without type 2 DM at baseline and with coronary heart disease (CHD) risk factor measurements in 1974-75. Diagnosis of type 2 DM during the follow-up was based on entitlement to re-imbursement for type 2 DM medication during 1975-1995, retrieved from national registers, self-report of type 2 DM or fasting blood glucose (> or = 6.7 mmol/L) in 1985-1986 (72% of the initial cohort re evaluated). During the follow-up (up to 1995) type 2 DM was diagnosed using the above criteria in 94 men (5.2%). At baseline, men who later developed type 2 DM smoked more (p = 0.01), and had significantly higher body mass index (BMI), systolic and diastolic blood pressure, pulse pressure, serum triglycerides, and fasting and one-hour blood glucose. In a subset of high-risk men, those who developed type 2 DM also showed signs of white-coat effect on blood pressure (p = 0.008). Already at baseline, the CHD risk score was 23% higher in future type 2 DM subjects (p = 0.008). Re-evaluation in 1985-1986 showed essentially similar results for risk factors, but in addition, LDL cholesterol without lipid lowering drugs was significantly lower (p = 0.0018) in type 2 DM subjects. During the follow-up, 23.4% of the men with type 2 DM developed CHD as compared to 13.4% of those without (p = 0.008). CONCLUSIONS: During a 20-year follow-up, several cardiovascular risk factors, including smoking, pulse pressure and the white-coat effect, predicted the development of type 2 DM in initially healthy middle-aged men. However, despite the higher incidence of CHD, development of type 2 DM was associated with lowered LDL cholesterol. PMID- 11213533 TI - L-carnitine reduces plasma lipoprotein(a) levels in patients with hyper Lp(a). AB - BACKGROUND AND AIMS: Elevated Lp(a) levels are a significant cardiovascular risk factor, particularly for young individuals and for subjects with concomitant high LDL cholesterol. Increased Lp(a) is believed to be linked to an enhanced production of the lipoprotein, controlled by genetic factors; it can be reduced by agents such as nicotinic acid, lowering free fatty acid inflow to the liver. METHODS AND RESULTS: L-carnitine, a natural compound stimulating fatty acid oxidation at the mitochondrial level, was tested in a double blind study in 36 subjects with Lp(a) levels ranging between 40-80 mg/dL, in most with concomitant LDL cholesterol and triglyceride elevations. L-carnitine (2 g/day) significantly reduced Lp(a) levels (-7.7% vs baseline and -11.7% vs placebo treatment), the reduction being more dramatic in the subjects with the more marked elevations. In particular, in the L-carnitine group, 14 out of 18 subjects (77.8%) had a significant reduction of Lp(a) vs only 7 out of 18 (38.9%) in the placebo group (chi 2 = 4.11, p = 0.0452). In a significant number of subjects the reduction of Lp(a) resulted in a return of this major cardiovascular risk parameter to the normal range. CONCLUSIONS: L-carnitine offers a potentially useful therapeutic agent for atherogenic conditions characterized by high Lp(a) levels, also in view of the excellent tolerability and essential lack of major side effects. PMID- 11213534 TI - Lipid-altering efficacy and safety of simvastatin 80 mg/day: worldwide long-term experience in patients with hypercholesterolemia. AB - BACKGROUND AND AIM: Clinical data suggesting that larger decreases in low density lipoprotein cholesterol (LDL-C) result in greater reductions in coronary heart disease events have led to the establishment of aggressive LDL-C targets for the treatment of hypercholesterolemia. In view of this, the efficacy and safety of a new maximum dose of simvastatin, 80 mg, were evaluated in 9 studies involving 2819 hypercholesterolemic patients. This report focuses on the combined results from the 4 main or Pivotal studies in which a total of 1936 patients received simvastatin 40 or 80 mg for 36 to 48 weeks. METHODS AND RESULTS: The Pivotal studies had similar randomized, multicenter, controlled, double-blind, parallel group designs. Their combined results demonstrated a significant advantage in the LDL-C-lowering effect for the 80 mg dose. At week 24, the mean percentage reductions (95% confidence intervals) from baseline in LDL-C for the 40 and 80 mg groups were -39.8% (-40.9, -38.7) and -45.7% (-46.5, -45.0) respectively (p < 0.001, between groups), and larger reductions in total cholesterol and triglycerides were also observed in the 80 mg group. Both doses were well tolerated. No new or unexpected adverse events were observed and the overall clinical event profiles were similar in the two groups. Clinically significant hepatic transaminase increases (> 3 times the upper limit of normal/ULN) and myopathy (muscle symptoms plus creatine kinase increase > 10 times ULN) occurred infrequently with both doses. Simvastatin 80 mg had a comparable efficacy and safety profile in women and men as well as in non-elderly and elderly patients. CONCLUSIONS: Simvastatin 80 mg provides additional LDL-C and triglyceride reductions compared to the 40 mg dose and has an excellent safety and tolerability profile. PMID- 11213535 TI - Helicobacter pylori infection in type 2 diabetic patients. AB - BACKGROUND AND AIM: A high prevalence of Helicobacter pylori (Hp) infection in diabetic patients has been described in recent years. This study investigates its prevalence in type 2 diabetics and its correlation with the degree of metabolic control and the presence of chronic complications. METHODS AND RESULTS: Forty-one consecutive type 2 diabetics (21 males, 20 females aged 46-78, mean 62) and 31 age-matched controls participated. Hp infection was assessed by means of the 13C urea breath test. Fasting glucose and glycated haemoglobin (HbA1c) levels were measured to evaluate metabolic control. Chronic complications were assessed by means of albumin excretion rate (AER), fundoscopy, vibratory perception threshold (VPT), ECG, clinical history of coronary, cerebral or peripheral arteriopathy, foot examination and cardiovascular autonomic function tests. A higher prevalence of Hp infection was found in diabetic than in control women (80% vs 37.5%; p < 0.05), whereas there was no difference between males. A higher prevalence correlated with macroangiopathy and neuropathy and higher BMI, blood pressure, fasting glucose and HbA1c values. By contrast, microangiopathy was significantly more prevalent (p < 0.05) in Hp negative (85%) than in Hp positive patients (48%). CONCLUSIONS: There is a high prevalence of Hp infection in type 2 diabetic women. The absence of microangiopathy may be a predisposing factor: microvascular changes in the gastric mucosa may create an unfavourable environment for the establishment or survival of Hp. PMID- 11213536 TI - Prevention of coronary heart disease in post-menopausal women. PMID- 11213538 TI - Obesity hypertension, salt sensitivity and insulin resistance. AB - AIM: To review human and animal data describing the complex interrelation between obesity hypertension, salt-sensitivity and insulin resistance. DATA SYNTHESIS: The first part of the article reviews the information available in the literature defining obesity hypertension as a salt sensitive form of hypertension and that links obesity hypertension to the presence of insulin. The second part reviews the four factors frequently cited as possible causes for this sodium retention: insulin resistance, alteration in the renin-angiotensin system, altered vascular responsiveness and alterations in the sympathetic nervous system. Special emphasis is given in an attempt to explain how each of these four factors can change pressure-natriuresis. CONCLUSIONS: There is clearly a strong relationship between obesity hypertension, sodium sensitivity and insulin resistance. The exact mechanism responsible for linking these three conditions is still unknown. However, there is ample evidence to suggest that insulin resistance, altered vascular responsiveness, altered function of the renin-angiotensin aldosterone system and altered function of the sympathetic nervous system are important in these three conditions. Further investigation is warranted to completely elucidate the complex relationship between insulin resistance, obesity hypertension and sodium sensitivity. PMID- 11213537 TI - Insulin resistance in essential hypertension: a psychophysiological approach to the "chicken and egg" question. AB - AIMS: High levels of plasma insulin have frequently been found in patients with high blood pressure. The causal role of insulin resistance in essential hypertension, however, is still debated. Epidemiological and clinical studies have not provided complete responses to the original pathophysiological speculations, while the suggestion that enhanced sympathetic tone may induce both insulin resistance and hypertension is gaining ground. DATA SYNTHESIS: Many studies indicate that the high sympathetic drive in hypertensive patients originates within the brain, while other studies show that insulin resistance is associated with reduced vasodilatory capacity and increased vasoconstrictive functional responses ascribed to endothelial impairment. The sympathetic overdrive and enhanced cardiovascular reactivity, detectable since the earliest stages of hypertension lead to endothelial damage and, hence, impair the vasodilatory response, peripheral blood flow and flow-dependent metabolism. Thus, the link between hyperinsulinemia and high blood pressure might lie in the vascular abnormalities secondary to elevated sympathetic tone and exaggerated hemodynamic stress response. CONCLUSIONS: Examination of the literature and the results of recent pilot studies of the stress systemic and regional hemodynamic reactivity in the present paper suggests that behavioral characteristics and cardiovascular stress responses play a pivotal role in determining the hyperinsulinemic state in hypertensive patients. High sympathetic tone, with consequent vascular impairment and altered functional responses, may be the primary event causing hyperinsulinemia and start very early in patients with high blood pressure. In turn, hyperinsulinemia further contributes to vascular damage and aggravates the metabolic and hypertensive disease. PMID- 11213539 TI - [Behavior of the pulp after dental trauma: diagnosis, sequelae, therapy]. PMID- 11213540 TI - [Early and late intraoral sequelae after radiotherapy]. PMID- 11213541 TI - [Severe sepsis, inflammation and coagulation: a close connection between physiological anticoagulants and improved prognosis] . PMID- 11213542 TI - [Antithrombin III concentrates in the treatmetn of sepsis and septic shock: indictions, limits and future prospects] . AB - Sepsis and septic shock are the most frequent cause of mortality in non cardiologic intensive care units. Mortality of the severe form is still elevated in spite of the progress in the antibiotic therapy and in the hemodynamic and respiratory support. The most frequent cause of death is the Multi Organ Dysfunction Syndrome (MODS). The excessive inflammatory reaction and the damage of the microvascular bed secondary to the inflammation and to the disseminated intravascular coagulation (DIC) are important pathogenetic factors. In the sepsis a complex system of cellular activation initiates the release and the interaction of activators and inhibitors of the inflammation (cytokines), the activation of the enzymatic cascade systems (coagulation, fibrinolytic and complement systems) and the synthesis of proteases and anti proteases. The activation of the coagulation system, uncontrolled by the fibrinolytic system with formation of fibrin in the micro vascular bed, has an important role in the MODS. Experimental data and clinical observations suggest a possible therapeutic role of antithrombin III (AT) in sepsis; its plasma concentration is constantly decreased in patients with sepsis or septic shock and the entity of the decrease is correlated with the severity of the clinical picture and the outcome. At has a double function: regulation of the coagulation system and anti inflammatory properties. The anti inflammatory properties depend in part on the binding to the glycosaminoglycans of the endothelial cells and the consequent release of prostacyclin (PGI2). The anti inflammatory effect is independent from the anticoagulant one. The preliminary studies on the clinical use of AT were carried out in small groups of patients with DIC associated with pathologies of different etiology and often in very critical conditions. In general the evaluation criteria were the improvement or the normalization of the laboratory data. The interpretation of the therapeutic effect of AT is difficult because the dysomogeneity of these studies. The effect on mortality is controversial. Recently three prospective, randomized, double blind studies have been published in patients with severe sepsis and septic shock. The results of the single studies are inconclusive but the limited number of patients included in each study may explain the results. A meta-analysis of the data referring to the patients with severe sepsis and septic shock evidenced an odd ratio (OR) of 0.43 with 95% confidential interval of 0.20-0.92 (p = 0.029). The preliminary analysis of the results of a phase III study is unconclusive. Time, dosage and duration of treatment are still open to question. In perspective AT may be used in other clinical conditions associated with activation of the hemostatic system (cardiac surgery, stem cell transplantation, burns) even though the preliminary results must be confirmed by prospective studies. All these data suggest severe sepsis and septic shock as main criteria for treatment. PMID- 11213543 TI - Measuring neuropathic pain. PMID- 11213544 TI - What about primary and secondary ARDS. PMID- 11213545 TI - [Sufentanyl in balanced anesthesia for neurosurgery. Comparative study with fentanyl] . AB - BACKGROUND: The aim of this study was to evaluate the effects of sufentanil in comparison with those of fentanyl during balanced anesthesia in patients undergoing neurosurgery. METHODS: EXPERIMENTAL DESIGN: prospective randomized study. SETTING: operating room in a neurosurgery University department. PATIENTS: 50 patients, ASA I and II with age ranging from 18 to 77 years were divided in two groups randomly. INTERVENTIONS: 25 patients received sufentanil as single bolus dose of 0.2 microgram/kg i.v. as premedication and supplemental bolus doses of 0.15 microgram/kg during the maintenance of anesthesia while the remainders received fentanyl 2.0 micrograms/kg as premedication and supplemental boluses of 1.5 micrograms/kg. All patients were induced with propofol 2.5 mg/kg, were intubated after cisatracurium 0.15 mg/kg for muscle relaxation, then were ventilated with sevoflurane and O2:N2O (1:1). MEASUREMENTS: heart rate, SAP, DAP and MAP were recorded at different times and ECG, ETCO2 and pulsoximetry were monitored continuously. Furthermore postoperative analgesia by VAS, recovery time and inspiratory concentrations of the volatile anesthetic were evaluated. Statistical analysis was carried out using ANOVA for repeated measures and Bonferroni "t"-test; a value of p < 0.05 was considered to be significant. RESULTS: Significant changes in MAP (at IOT and 1 and 2 min after IOT), in HR (at IOT) and in RPP (at IOT and 1, 2 and 3 min after IOT) were recorded in group F. Recovery time was shorter in group S than in group F and postoperative analgesia was more prolonged in group S. Inspiratory concentrations of volatile agent were lower in patients treated with sufentanil than in those treated with fentanyl. CONCLUSIONS: In patients treated with sufentanil a better cardiocirculatory stability was achieved with lower inspiratory concentrations of volatile agent and a well relaxed brain. Sufentanil can be considered a valid alternative to fentanyl as analgesic agent in balanced anesthesia for neurosurgery. PMID- 11213547 TI - [Anesthesiologic considerations in Cornelia de Lange syndrome]. AB - BACKGROUND: Retrospective study in pediatric patients with Cornelia de Lange syndrome undergoing different surgical operations, in order to critically evaluate the anesthesiologic aspects of this syndrome. METHODS: Between January 1997 and December 1998, 42 patients undergoing diagnostic examinations (esophagogastroscopy, oculistic visit) or surgery (total exodontia, fundoplicatio for esophageal reflux, correction of labiopalatoschisis) have been studied. The anaesthesiologic technique has been similar for all the cases. RESULTS: Any particular difficulty or inconvenience in comparison with patients with the same range of age, or particular intraoperative difficulties have been observed. In only one patient the McCoy laryngoscope was used due to difficult intubation (Cormack and Lehane III). CONCLUSIONS: Short neck, ogive palatum, cleft palate, micrognatia, urogenital and gastroenteric anomalies, esophageal reflux, together with heart defects (15% of cases), can complicate the peri and postoperative period in these patients. A careful preoperative evaluation and a careful perioperative management, may decrease anesthetic complications in Cornelia de Lange syndrome to the same range of normal patients. PMID- 11213546 TI - [The effects of remifentanil on hemodynamic response to intubation. A comparative study with fentanyl] . AB - BACKGROUND: The aim of this study was to evaluate the effects of remifentanil in comparison with those of fentanyl on the hemodynamic response to orotracheal intubation. METHODS: EXPERIMENTAL DESIGN: prospective comparative and randomized study. SETTING: operating room in a neurosurgery department at University. PATIENTS: 50 patients, ASA I or II with age ranging from 32 to 64 years were divided in two groups randomly. INTERVENTIONS: 25 patients received fentanyl as single bolus dose of 2.0 micrograms/kg and atropine 0.01 mg/kg i.v. as premedication while the remainders received atropine 0.01 mg/kg i.v. and remifentanil 0.2 microgram/kg/min as infusion. All patients were induced with propofol 2.0 mg/kg and cisatracurium 0.15 mg/kg for muscle relaxation and were intubated 4 min after induction of anesthesia. MEASUREMENTS: Heart rate, SAP, DAP, MAP and RPP were recorded at different times: baseline, induction, intubation, 1, 2, 3 and 4 min after intubation; ECG and pulsoximetry were monitored continuously. Statistical analysis was carried out using ANOVA for repeated measures and Bonferroni t-test a value of p < 0.05 was considered to be significant. RESULTS: Significant increases in PAS were recorded, at intubation and at 1 min after in patients treated with fentanyl; in the remifentanil group significant decreases in SAP at induction and at 4 min after intubation were recorded. HR increased significantly at intubation and at 1, 2 and 3 min after in the fentanyl group. RPP showed a significant decrease at induction in the remifentanil group and significant increases at intubation and at 1, 2 and 3 min after in patients treated with fentanyl. CONCLUSION: In conclusion remifentanil was found to properly control the hemodynamic response to intubation in comparison with fentanyl. PMID- 11213548 TI - [Anesthesia with sevoflurane and orotracheal intubation for pediatric ophthalmic surgery of medium length in day hospital] . AB - BACKGROUND: The aim of this study was to evaluate the discharge rate of children undergoing ophthalmic surgery of medium length (69-120') in a day-hospital regime under general anesthesia with orotracheal intubation and using Sevoflurane as the only anesthetic agent. METHODS: EXPERIMENTAL PROTOCOL: prospective study. SETTING: the study was carried out in the operating theatre of the Ophthalmic Clinic at Florence University. PATIENTS: 58 pediatric patients aged 2-10 years, ASA I-II, 13-34 kg. OPERATIONS: correction of strabismus, cataract, glaucoma, palpebral ptosis and intubation of lacrimal tracts. Parameters measure: Any signs of reactivity in the airways to Sevoflurane on induction or reawakening (cough, bronchospasm, laryngospasm and psychomotor agitation), hemodynamic variables (heart rate and NIBP); reawakening time (from turning off the vaporiser to extubation), discharge time from recovery room (SatO2 > or = 97% in ambient atmosphere), discharge time from hospital (stable vital signs, response to simple and complex commands). RESULTS: The mean reawakening time was 7 min, discharge time from the recovery room was 20 min, discharge time from the hospital 80% after four hours, 100% after six hours. No respiratory and/or cardiovascular complications were reported nor psychomotor agitation. CONCLUSIONS: General anesthesia with Sevoflurane and Atracurium was found to be a realistic and reliable technique in pediatric ophthalmic surgery of medium length performed in day hospital. PMID- 11213550 TI - Cost analysis of an Italian ICU. AB - BACKGROUND: Cost reduction is an important issue in medicine today, especially when considering ICUs, since they account for a large percentage of all hospital expenditure. Through a retrospective analysis of the data regarding the expenses incurred during the years 1996-97, we have been able to evaluate the total costs of our ICU and the influence that each component had on the final costs, thus gathering the necessary information for the improvement of the unit itself. METHODS: Retrospective analysis of a 5-bedded multidisciplinary ICU activity over a two-year period (1996-1997). Cost-related data have been supplied by the Hospital Administration as to wages, infrastructures, equipment buying and maintenance; by Hospital Pharmacy as to drugs and devices supplies; and by Laboratory and Radiology as to diagnostic investigations. RESULTS: According to our experience, physicians and non-medical staff account for more than 50% of the total expenditure--the latter slightly prevailing. Furthermore, we have assessed that the cost distribution is hardly comparable to that reported by other authors. CONCLUSIONS: It is useful to analyse the total distribution and to evaluate their nature only to gain the necessary data that will lead to a more effective management of the unit. Nevertheless, this methodology is valid within the cost analysis of our ICUs but the ICUs of other countries show great differences in the way they are structured and some of the use more reliable activity-based costing methodology. PMID- 11213549 TI - Italian experience with the cuffed oropharyngeal airway (COPA). A prospective, observational study. AB - BACKGROUND: The cuffed oropharyngeal airway (COPA) has been recently introduced into the market, but few is known about its clinical use in Italy. We therefore conducted a prospective, observational investigation to evaluate the use of this new extra-tracheal airway in clinical practice. METHODS: Anesthesiologists participating in the study received a simple questionnaire where data concerning anthropometric variables, surgical procedure, type and doses of drugs used to induce and maintain general anesthesia, type of ventilation during the procedure, and occurrence of untoward events during either COPA placement, general anesthesia maintenance, or postoperative period were prospectively recorded. The number of previously placed COPA, and the adequacy of airway control (subjective four point scale: excellent, good, fair, and poor) were also assessed. RESULTS: A total of 210 patients (139 female and 71 male) were prospectively studied. General anesthesia was induced with propofol in 204 patients (98%), sodium thiopental in 3 patients (1.5%), and midazolam in 1 patient (0.5%); while only one patient received muscle relaxants (0.5%); 126 patients (64%) were spontaneously breathing while 71 patients (36%) received positive pressure mechanical ventilation. No differences in the incidence of untoward events was reported between spontaneously breathing and mechanically ventilated patients. No differences in the incidence of untoward events were reported according to the number of previously placed COPA. Difficulties in COPA placement were reported in 7 patients with normal dentiture (5%) and 9 patients (39%) with dental prosthesis (p = 0.003), (Odds Ratio: 5.1; Cl95%: 3.0-8.7). Furthermore, airway obstruction was more frequently reported in patients with dental prosthesis (8% vs 0%; p = 0.002). The seal pressure was higher in mechanically ventilated (17 +/- 10 cm H2O) than spontaneously breathing patients (10 +/- 8 cm H2O), (p = 0.0005), while a sealing pressure higher than 12 cm H2O was associated with an increased risk for postoperative sore throat (Odds ratio: 4.3; Cl95%: 2.6-7.1; p = 0.002). Airway control was graded as excellent in 61.4% of cases by physician previously placing more than 50 COPA, compared with only 26.5% when less than 50 COPA had been previously placed (p = 0.0005). CONCLUSIONS: COPA provided as safe and effective airway management in mechanically ventilated patients as that observed during spontaneous breathing. Experience with COPA placement had no effects on the placement success rate or incidence of untoward events, but improved the quality of airway control. PMID- 11213551 TI - SCS in intractable angina. AB - Despite a wide range of therapeutic choice in the treatment of angina pectoris, there is a small but increasing population of patients that doesn't benefit of conventional therapy and whose life is invalidated by frequent attack of anginal pain. For this population, nonresponders to drug therapy not suitable for revascularization (coronary bypass surgery, angioplasty), neurostimulation of dorsal column has been described as an effective and safe therapy. The mechanism of action is not completely known, but is safety is sufficiently established. It may become a useful choice in the treatment of patients with intractable angina. PMID- 11213552 TI - [Bioethical interpretation of intensive care] . AB - The bioethical interpretation concerns both those receiving intensive care (IC) and the nature of the treatment itself. The principle of autonomy expressed in the doctor-patient relationship is achieved through the use of informed consent and may also be used in the unique context of patients in IC. Organ-function replacement treatment raises the ethical question of the definition and management of the limit to treatment. The appropriateness of IC can be defined by clinical and ethical criteria and aims to avoid inappropriately excessive treatment. In order to improve the decision-making process involving bioethical questions, the authors outline a number of working approaches: the use of informed consent even in IC, the possible role of Advanced Directives in IC, epidemiological studies, operator training. PMID- 11213553 TI - Total intravenous anaesthesia without muscle relaxants in a child with diagnosed Duchenne muscular dystrophy. AB - The case of a 3 year old child, affected by Duchenne muscular dystrophy, who underwent adenoidectomy and bilateral myringotomy, is reported. Total intravenous anaesthesia (propofol 1% infusion (160 micrograms kg-1min-1) and remifentanil (0.55 microgram kg-1min-1) without any muscle relaxants was used. The postoperative period was uneventful. PMID- 11213554 TI - [Italian version of "The Neuropathic Pain Scale"] . PMID- 11213555 TI - Histochemistry and cytochemistry of nuclear receptors. AB - Receptors of steroid hormones, thyroid hormones and several kinds of vitamins have been shown to act as nuclear transcription factors and to form a nuclear receptor (NR) family. Histochemical techniques including autoradiography using radio-labeled ligands, immunohistochemistry and in situ hybridization histochemistry, have displayed that target cells of these receptors are distributed not only in the classical target organs but also widely in a variety of tissues; these techniques can demonstrate the presence of receptor proteins and mRNAs, even though they are expressed in a small cell population of tissues. On the other hand, many studies have been performed to demonstrate the interaction between NRs and nuclear and cytoplasmic proteins, and to clarify the mechanism of transcriptional regulation through NRs in artificial conditions which are created in gene transfer experiments or under cell-free conditions. Some data coincide with those obtained from histochemical techniques, however, some histochemical data do not support the results of studies in vitro. This review focuses on the following topics: histochemical methodologies to detect NRs, the distribution and function of NRs in the tissues, the intracellular and intranuclear localization of NRs, roles of gonadal steroid receptors and their ligands on developing tissues including cell communications such as mesenchymal stromal interaction, and the interaction between other cellular components and NRs. In addition, the agreement and disagreement between the results of histochemical studies and those from the experiments in the model systems or in vitro are discussed. PMID- 11213558 TI - [Index 1857-2000 on cd-rom; Dutch Journal of Medicine may be ordered on its own web page]. PMID- 11213556 TI - [Congenital infection: diagnostic serology of the mother not always definitive]. AB - In 2 infants, a girl and a boy, congenital viral infection was diagnosed in the neonatal period. The prenatal examination (serologic investigation for Toxoplasma gondii, rubella virus, cytomegalovirus, herpes simplex virus and syphilis (TORCHES)) was negative. In both cases prenatal ultrasonography was abnormal and suggested intrauterine infection. The infants were born with typical symptoms of multisystem disease, known as symptomatic congenital cytomegalovirus infection (jaundice, petechiae, hepatosplenomegaly, intrauterine growth retardation, microcephaly and cerebral calcifications) and congenital rubella syndrome (intrauterine growth retardation, congenital heart disease, cataract, hepatosplenomegaly and cerebral calcifications), respectively. Both had severe cerebral damage. To diagnose severe congenital infection in the first trimester of pregnancy in presence of congenital anomalies in utero there are other possible methods than TORCHES investigation, such as polymerase chain reaction and virus culture in amniotic fluid or in foetal blood obtained by cord puncture. PMID- 11213559 TI - [Roaming through methodology. XXX. The capture-recapture method]. AB - The capture-recapture method is useful for the estimation of the incidence and prevalence of a disease if there exist multiple lists that can be linked. Some assumptions have to be fulfilled for the estimate to be adequate. For example, for every list every individual should have the same probability to be on the list, and the lists should be independent. In case of two lists one has to assume that these are independent in order to get an estimate. When three or more lists are available this strong assumption may be mitigated. PMID- 11213560 TI - [Roaming through methodology. XXXI. Estimating partially hidden populations: heroin addicts in Amsterdan]. AB - To estimate the size of a partly hidden population the capture-recapture method can be used. The estimation is based on analysis of the overlap between several samples of the population of interest. The quality of this capture-recapture estimation highly depends on whether the assumptions of the method are or are not met: samples should be independent, the population should be closed, the overlap should be recognised, and samples should contain only individuals originating from the population of interest. Violation of these assumptions may lead to a serious underestimation or (more often) overestimation. The number of problematic heroin addicted people in Amsterdam was estimated on the basis of registered numbers in the easily accessible methadone programme of the municipal health organisation, in the police station methadone treatment programme, and in the hospital registration in the first quarter of 1997: 4130 (95% confidence interval: 3750-4570). PMID- 11213561 TI - [Drug treatment of erection disorders in patients with cardiovascular disease]. AB - Erectile dysfunction is a frequent condition in cardiovascular patients. Since the arrival of oral erection-supporting medication, patients want to know how safe sexual activity is in cardiovascular disease in general and during use of erection-supporting medication in particular. Sexual intercourse with a steady partner causes no more cardiovascular risk than normal daily activities such as ironing, 2 kilometers of walking without climbing, paperhanging, playing golf or gardening. The relative risk of myocardial infarction during sexual activity is not significantly higher than for healthy persons. The incidence of cardiovascular morbidity and mortality is not higher among users of sildenafil. Sildenafil is contraindicated in patients using long-acting nitrates or who may need to use short-acting nitrates, because the combination may cause a sharp fall of the blood pressure. No interactions have been observed with beta-receptor blockers, calcium antagonists, thiazide and loop diuretics and ACE inhibitors. Before prescribing a symptomatic (pharmaceutical) treatment for patients with an erection disorder, attention should be given tot the sexological, psychological and medical backgrounds of the disorder. Secondary prevention of atherosclerotic risk factors is also important: regulation of blood pressure and blood sugar level, hyperlipidaemia and obesity, as well as a change of lifestyle (giving up smoking, adapting of diet and more physical exertion). Patients with a very low cardiac capacity should be advised to refrain from treatment of the erection disorder. PMID- 11213562 TI - [Diagnostic image (22). Partial torsion of ovarian tumor]. AB - In a 28-year-old woman recurrent abdominal pain was caused by a partially torded cystic teratoma of the ovary. PMID- 11213563 TI - [From gene to disease; from polycystines to polycystic kidney disease]. AB - Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease that results in multiple cysts in the kidneys and other organs and leads to endstage renal failure relatively late in life. The disease results from mutations in one of two independently segregating genes that under normal conditions produce polycystines. Polycystines are membrane proteins that form a complex involved in signal transduction in epithelial cells. Genetic heterogeneity explains in part the various ADPKD phenotypes. PMID- 11213564 TI - [Considerable underreporting of malaria in the Netherlands; a capture-recapture analysis]. AB - OBJECTIVE: To estimate the completeness of notification of malaria by physicians and laboratories in the Netherlands. METHOD: Capture-recapture analysis was applied to three incomplete, partially overlapping registers of malaria cases in 1995 and 1996: a laboratory survey, the Notification Office and the hospital admission registration. RESULTS: The average response of the 107 laboratories approached was 83.6% over both years. In 1995 and 1996 581 and 535 malaria cases respectively were microscopically diagnosed. In each year physicians officially notified 311 patients. 350 and 330 patients respectively were admitted to hospital. Capture-recapture analysis estimated the total number of new malaria cases at 933 (95% confidence interval: 849-1072) in 1995 and at 774 cases (740 821) in 1996. The estimated completeness of notification in 1995 and 1996 was therefore 33.3% and 40.2% for physicians and 62.3% and 69.1% for the laboratories. CONCLUSION: Laboratory-based notification, introduced in the Infectious Diseases Act, can considerably increase the number of officially reported malaria cases as compared with notification by physicians. However, approximately one-third of the estimated number of cases may still go unreported. PMID- 11213565 TI - [Diagnostic value of prenatal MRI in fetus with intracranial anomalies diagnosed by ultrasonography]. AB - OBJECTIVE: To determine the value of prenatal MRI in the third trimester in the foetus with intracranial lesions established by ultrasonography. DESIGN: Descriptive. METHOD: During a period of one year, prenatal MRI was performed in 12 patients after ultrasonography had revealed intracranial lesions in the foetus. Postnatally, ultrasonography, MRI or postmortem examination of the brain was performed in 11 children. The MRI examination was carried out in a 1.5 Tesla field. Rapid, T2-weighted images were obtained. To immobilize the child, the pregnant women were sedated. RESULTS: In 5 cases, prenatal ultrasonography and prenatal MRI resulted in the same diagnosis. In seven cases, MRI provided more information. Postnatal examination confirmed the prenatal diagnosis in 10 of the 11 cases. In one case, maceration rendered supplementary examination impossible. CONCLUSION: MRI may be regarded as a valuable alternative diagnostic aid if prenatal ultrasonography is incomplete or the findings are uncertain or limited. PMID- 11213566 TI - [Fever and chills due to leptospirosis after travel to Thailand]. AB - Two weeks after rafting on a river in Thailand a Dutch 54-year-old male experienced chills and high fever. While rafting he had wounded his hand. Because of the history (water contact, the wound, high fever with chills), of the findings at examination (fever, conjunctivitis) and of the laboratory findings (leukocytosis, albuminuria, disturbance of liver enzymes), a clinical diagnosis of 'leptospirosis' was made. This was confirmed by serological tests and culturing of Leptospirae from the blood. Leptospirosis is a zoonosis, in man associated with certain occupations, water sports and inundations. The clinical picture varies from a mild febrile disease (sometimes pyrexia of unknown origin) to a severe condition with kidney and liver failure, bleeding tendency, lung oedema (Weil's syndrome). In travellers with fever, water contact, leukocytosis and neutrophilia, leptospirosis must be considered and specific diagnostic tests applied. PMID- 11213567 TI - [Clinical thinking and decision-making in practice. A pregnant Turkish woman with a liver tumor]. PMID- 11213568 TI - [Stereotaxic irradiation of vestibular schwannoma (acoustic neurinoma)]. PMID- 11213569 TI - [Diagnostic imaging in vascular diagnosis]. AB - Previously, vascular imaging was done exclusively using angiography (X-ray projectional imaging of vessels opacified by iodinated contrast media). Recently angiography especially is used in combination with angioplasty (percutaneous enlargement of a closed or stenotic vessel). There has been a change from invasive to non invasive procedures. New developments in computed tomography (CT), magnetic resonance imaging (MR) and ultrasound have reduced the indications for the invasive digital subtraction angiography (DSA). Further improvement especially im MR-angiography and colour-coded dopplersonography will cover all primary diagnostic vascular examinations. PMID- 11213570 TI - [Treatment of peripheral arterial occlusive disease]. AB - The choice of therapy for peripheral artery occlusive disease depends on functional stage, site and extent of vascular lesion, pathogenesis, and the individual needs of the patients. In stage I (according to Fontaine) the risk factors are sought and treated. In stage II walking exercise is the main pillar besides vasoactive drugs and secondary drug prevention. Transluminal angioplasty is recommended if vascular lesions are suitable (short stenoses or occlusions in iliac a/o femoro-popliteal arteries). Surgery may be performed in aorto-iliac arteries but only exceptionally in femoro-popliteal disease. In stage III/IV or chronic critical ischemia every possibility for revascularisation must be considered. In acute stages immediate therapy is necessary. In our hands catheter techniques (thrombolysis a/o aspiration) are the first line approach on the femoro-popliteal level while occlusions on aorto-iliac level are left to surgery. PMID- 11213572 TI - [Comment on Hermann Feldmeier: West Nile virus ante portas]. PMID- 11213573 TI - [Risk factors for arteriosclerosis]. AB - The arteriosclerotic damage of the arterial endothelium is initiated by risk factors like dyslipidemia, hypertension, diabetes mellitus, and smoking, which account for the majority of vascular morbidity and mortality. Interventional studies confirmed the causative role of hyperlipidemia, particularly of the modified LDL-cholesterol. A large number of epidemiological and interventional studies identified hypertension as another risk factor and showed the correlation between lowering blood pressure and the reduction in micro- and macrovascular complications. Diabetes mellitus decreases the life expectancy on average by 10 years, mainly due to cardiovascular disease. However, intensive control of blood glucose and blood pressure achieved a significant and clinically important reduction in death and complications related to diabetes. Smoking is a main risk factor for peripheral arterial disease and causes advanced arterial lesions in the younger people. Novel risk factors have been identified and contribute to the elucidation of the atherogenic process. PMID- 11213571 TI - [Surgical therapy of acute and chronic arterial occlusions below the inguinal ligament]. AB - The history and physical examination are extremely important in the management of vascular surgical patients because a correct diagnosis can usually be made on the basis of information obtained from these two modalities. The severity of the chronic occlusive process leads to characteristic symptoms in the extremity: claudication, rest pain, skin ulcerations and gangrene. Chronic progressive lesions permit enlargement of collateral blood supply which, for a time, minimizes the severity of symptoms. Milde degrees of arterial insufficiency (claudication) can be treated conservatively. Unreconstructed chronic critical ischemia predicts a poor outcome in terms of survival and limb salvage. The outlook with arterial reconstructive surgery is by far better. Arteriography ist the most reliable diagnostic test for occlusive lesions. It ist essential for the operative planning. Vein-bypass procedures are, if feasible, very effective in most cases. Acute embolic occlusion: Sudden occlusion of a previously patent artery is usually a dramatic event producing severe ischemia of the distal tissue. The characteristic symptoms and signs are the 5 P's: pallor, pain, paresthesia, paralysis, pulselessness. Emergent restoration of blood flow by operation may be essential to prevent limb loss. Milder forms of ischemia (acute thrombosis--acute or chronic disease) can be treated initially with intravenous heparin if the extremity is not threatened (minimal sensory loss, no muscle weakness). Elective surgery at a later date is highly successful. PMID- 11213574 TI - [Diagnosis of arterial occlusive disease: what does angiology have to offer?]. AB - Peripheral arterial disease is common in the elderly patient. The clinical symptoms are varied from claudication to the acute ischemic syndrome. The diagnosis can be suspected from history and clinical examination. Additional investigations like leg pressure measurements, oscillography and duplex sonography confirm the diagnosis. These investigations further quantify the extent and the localisation of the occlusive disease and are needed to choose the treatment. Treatment modalities are conservative, interventional by catheters and surgical. Further angiographic examinations are rarely needed. The interdisciplinary approach together with surgeons and radiologists is most important. PMID- 11213575 TI - [Some comments about hemochromatosis]. PMID- 11213576 TI - [Prevalence of hereditary hemochromatosis among healthy workers. Diagnostic value of transferrin saturation assay]. AB - AIM: Hereditary hemochromatosis is the most common inherited disorder in white population (2-8 cases per 1000 habitants). Hemochromatosis is characterized by increased intestinal absorption of iron leading to its deposition into multiple organs. An early diagnosis and proper management with frequent phlebotomies are known to improve life expectancy and quality of life. Diagnosis is suggested by an elevated Transferrin saturation (TS) (more than 60%). METHOD: Prospective study of the level of TS among 1131 healthy workers, who came to the Security and Hygiene Official Centre for their annual revision had been undertaken. RESULTS: Twenty-wo workers had high TS; in 10 of them the increase of TS was confirmed on repeated determinations. Liver biopsy was performed in six (and refused by the other four), eventually a diagnosis of hemochromatosis was confirmed in three (in group prevalence of 2.6 per 1000 people). CONCLUSIONS: In our experience, TS is the most appropriate initial screening test for detecting hereditary hemochromatosis in a normal population. PMID- 11213577 TI - [Correlation between mantoux and tuberculin's fraction from delayed hypersensitivity skin test, in a cohort from HIV-1 positive patients, in function of immunodeficiency level, and active tuberculosis incidence]. AB - OBJECTIVES: The aim of this work was to assess cellular immunity using the multitest CMI and relate its results with lymphocyte CD4 counts, and the risk to developed active tuberculosis if the multi-test's tuberculosis papula was positive. METHODS: Prospective longitudinal follow-up of 342 IDU patients, 210 infected with HIV-1 and seronegative 132 patients. The cohort study was 165 IDU HIV-1 positive patients (128 men, 37 female). Ages was 18 to 45 years. Study time were 25 months (8-25). Tuberculin skin tests and multitest IMC were performed at baseline and each three months, and screening from active tuberculosis were performed all study when necessary was considered. RESULTS: Actived tuberculosis developed in 9.25 cases per one hundred persons and year from follow-up in the ranges with better immunologic status (Score from PHR > 10 mm). There are an significative correlation between tuberculosis skin test diameter and PHR tuberculin fraction papula. CONCLUSIONS: PHR performed with Multitest IMC is an useful test to evaluate cellular immune system, and HIV-1 positive patients with energy in this test or positive tuberculine fraction must be considered to isoniazid (9 months) prophylaxis. PMID- 11213578 TI - [Extrapulmonary tuberculosis in our area. Forms of presentation]. AB - OBJECTIVE: To analyse the distribution of the extrapulmonary forms of presentation of tuberculosis (EFP) in our health district. MATERIALS AND METHODS: The medical records of patients diagnosed with extrapulmonary tuberculosis attending the Tuberculosis Prevention and Control Unit of the Santiago Health District were reviewed over a three years period. The classification of EFP was: extrapulmonary forms (EF), disease outside the lung; mixed forms (MF), the presence of both pulmonary and extrapulmonary tuberculosis; disseminated forms (DF), the presence of two or more extrapulmonary locations; and miliary TB, which was defined by a diffuse pulmonary radiographic pattern or diagnosis was undertaken by necropsy. RESULTS: A total of 921 tuberculosis infected patients were observed, of which 370 (40.2%) were extrapulmonary forms; of these, 199 were men and 171 women (mean age was 36.9 years, range 19-68). The distribution of EFP was: 307 EF (83%) of which 140 (45.6%) were pleural, 87 (28.3%) ganglionary, 16 (5.2%) intestinal, 14 (4.5%) bone and joint, 11 (3.6%) genitourinary, 11 (3.6%) cutaneous, 10 (3.3%) meningeal, and other locations 18 (5.9); MF 38 cases (10.3%); DF 8 cases (2.1%) and miliary TB 1 cases (4.6%). In HIV infected patients 17 EF (77.3%), which were mainly ganglionary (64.7%); 4 DF (18.2%); and 1 miliary TB (4.5%) cases were observed. CONCLUSIONS: Our findings confirm the high incidence of extrapulmonary TB, similar to the number of pulmonary forms. Our experience shows a significant modification to the classical presentation of the disease, and thus the need for sensitivity in locating the disease. PMID- 11213579 TI - [Value of the detection of serum thyroglobin and I-131 scintigraphy in the follow up of differentiated thyroid cancer]. AB - OBJECTIVES: The objective of this work has been to know the sensitivity of serum thyroglobulin and I-131 scintigraphy in the detection of thyroid remnants or metastases, and to evaluate the predictive value of serum thyroglobulin in the follow-up of differentiated thyroid cancer patients. METHODS: We have carried out a retrospective study of 218 patients with differentiated thyroid cancer, with detection of serum thyroglobulin levels and I-131 scintigraphy in clinical status of hypothyroidism, after to perform thyroidectomy and between six and nine months later. We have rejected 16 and 14 patients who have had presented high serum levels of thyroglobulin, or an incomplete follow-up. RESULTS: Our results showed a good correlation of both parameters (92%). The sensitivity of TG and I-131 scan was 85% and 90% respectively, and superior to 90% for both procedures in the diagnosis of the osseous and lung metastases. The sensitivity of I-131 scan and TG was 100% and less to 70% in the detection of thyroid remnants and regional lymphatic nodes. The positive and negative value of TG was 99% and 91%, respectively, with a total of 24 false negative results. CONCLUSIONS: Considering this study, we believe that both techniques are complementary, with a lower sensitivity of serum TG in the detection of thyroid remnants and regional lymphatic involvement, and a negative predictive value that does not permit to accomplish the follow-up of differentiated thyroid cancer patients, considering exclusively the results of this tumoral marker. PMID- 11213580 TI - [Cytomegalovirus diarrhea as a diagnostic index for AIDS]. AB - We report a case of a male 49 years old, without clinical history, excepting rape in 1996, that was admitted to the Emergency Room of HGUGM because of diarrhea 6 months duration, plus fever (39 degrees C) in the last 2 months. He was diagnosed of infection by the Human Immunodeficiency Virus (HIV), with serum antigenemia (70 cells), and colonic biopsy positives for Cytomegalovirus, and a normal colonoscopy. Cytomegalovirus colitis is the major etiologic infectious agent in patients with AIDS-associated diarrhea, although it can be the diagnostic index for AIDS in a few cases. PMID- 11213581 TI - [Listeriosis: an infrequent infection in patients with HIV]. AB - Although resistance to Listeria monocytogenes infection requires intact T-cell mediated immunity, listeriosis is an infrequent problem in patients with HIV infection and only about 50 patients have been reported to date. Only two patients with HIV and L. monocytogenes have been attended in our hospital since the beginning of aids epidemic in 1981. Case 1: a man with HIV and 364 CD4+ cells/mm3 presented fever and occipital headache. The cerebral scan was normal and L. monocytogenes grew in licuor culture. He was outcome after treatment with ampicillin and tobramycin. Case 2: a 47 years old man with HIV, 44 CD4+ cells/mm3 and hepatic virus C cirrhosis was admitted to the hospital because fever and abdominal distension. He was on menstrual pentamidine prophylaxis for Pneumocystis carinii pneumonia (PCP). Bacterial peritonitis was diagnosed and the patient begun treatment with ceftriaxone. The patient dead 72 hours later with hepatic encepholopathy. Postmortem L. monocytogenes grew. Listeriosis is an infrequent disease in patients with HIV that causes difficult diagnostic problems, principally in patients without prophylaxis with cotrimoxazole for PCP. PMID- 11213582 TI - [Repeated hemoptysis for foreign body bronchial aspiration: presentation of a case and review of literature]. AB - The foreign body aspiration is more frequent in children. The most usual etiology is the foreign bodies of vegetable nature, which can not be observed in the chest radiograph. The clinic signs are varied, including shortness of breath, cough and wheezing. Hemoptysis is a rare symptom, whose arising is generally connected with the existence of bronchiectasis. We present the case of a child who showed repeated hemoptysis and focal neumonitis due to Eikenelle corrodens three years after the aspiration of a spike. The diagnosis of the bronchial aspiration obtained after The most unusual in this case is the clinic manifestation of repeated hemoptysis, together with the long connected to the existence of foreign body inside the bronchus. PMID- 11213583 TI - [Spontaneous pneumomediastinum and idiopathic pulmonary fibrosis]. AB - The association between pulmonary fibrosis and pneumomediastinum is infrequent. Computed tomography is the suited method for the detection of small pneumomediastinum, which is difficult to detect by chest radiography. A case of idiopathic pulmonary fibrosis, with frequent and violent cough, with pneumomediastinum and cervical subcutaneous emphysema, without pneumothorax, probably caused by rupture of bullae is presented. The outcome was favourable with symptomatic treatment. PMID- 11213584 TI - [Pyogenic liver abscess as a complication of Crohn's disease]. AB - Pyogenic liver abscess in patients with Crohn's disease is not common, but the mortality has been reported to be high if diagnosis and treatment is delayed. Intra-abdominal abscesses, fistulous disease, and steroid therapy have all been reported to be important predisposing factors in the pathogenesis of this entity. We present a patient with Crohn's disease in whom multiple abscesses were encountered in the right lobe of the liver. The diagnosis of liver abscess was established by abdominal computed tomography and the patient was treated by percutaneous catheter drainage. Awareness of this rare complication is important because diagnosis is difficult to make and a high index of suspicion is required. Once suspected, aggressive diagnostic workup and treatment is indicated. Most patients with liver abscess can be successfully managed by percutaneous catheter drainage combined with antibiotic therapy if it is diagnosed before extensive necrosis has occurred. PMID- 11213585 TI - [Evidence-based medicine tratment of chronic viral hepatitis B and C]. AB - Worldwide, viral hepatitis is the most common cause of jaundice, chronic liver disease, cirrhosis and hepatocellular carcinoma. Although mayor advances have been made in the field of treatment and prevention, there is not a totally satisfactory treatment for each of both diseases. They account for a high percentage of the etiology of viral hepatitis and have a tendency towards chronicity and developing cirrhosis, resulting in a tremendous waste of medical resources. On the other hand, their treatments are long-term ones and the drugs, which are employed, are expensive. Thus, it is necessary to make an evidence based medicine approach in this particular kind of illness to obtain the best benefit/cost ratio. In this current review, we analyzed the different drugs and therapeutic schedules, which are used in the chronic viral hepatitis B and C, and as well as their obtained response. PMID- 11213586 TI - [Monoclonal gammapathy IgG kappa in patients with Sjogren syndrome. Apropos of a case]. PMID- 11213587 TI - [Alteromona putrefaciens pleural empyema]. PMID- 11213588 TI - [Hypovolemic shock by aortoenteric fistula]. PMID- 11213589 TI - [Patient with HIV infection and acromegaly]. PMID- 11213590 TI - [Myasthenia gravis after tetrazepam treatment]. PMID- 11213591 TI - [Pulmonary embolism in the Internal Medicine Service (1992-97)]. PMID- 11213592 TI - [Severe thrombocytopenia related to granulocyte-macrophage colony-stimulating factor (rHU-GM-CSF)]. PMID- 11213593 TI - [Pneumocystis carinii pneumonia in patients with HIV infection. Review of 70 cases]. PMID- 11213594 TI - Multiple risk factor intervention in type 2 diabetes: an opportunity not to be missed. PMID- 11213595 TI - Clustering of cardiovascular risk factors in type 2 diabetes mellitus: prognostic significance and tracking. AB - AIM: Little attention has been paid to the prognostic significance and tracking effect of risk factor clusters characteristic of type 2 diabetes mellitus. We studied the clustering of eight cardiovascular risk factors (smoking, high body mass index, elevated systolic blood pressure, high serum, low density lipoprotein (LDL) cholesterol, high serum LDL triglycerides, low serum, high density lipoprotein (HDL) cholesterol, high fasting blood glucose and high plasma insulin concentration) and their effect on the prognosis and the tracking effect. METHODS: This study is a population-based prospective follow-up of newly diagnosed type 2 diabetic subjects (n = 133, aged 45-64 years) in Eastern Finland. The following end points were used: all-cause mortality, cardiovascular mortality, and incidences of first myocardial infarction and first stroke. Furthermore, we studied the 'tracking effect' of the risk factor clusters during the 10-year follow-up period. RESULTS: When the clustering of risk factors typical of type 2 diabetes mellitus was taken into account, all-cause mortality increased from 28.6% to 50.0% (p < 0.05) and cardiovascular disease mortality increased from 14.3% to 50.0% (p < 0.01) depending on the number of risk factors present. The incidence of first myocardial infarction increased from 0% to 40.0% (p < 0.05) as the number of risk factors increased from 0 to 5. In survivors, the proportion of individuals with no risk factors decreased and the proportion on individuals with three to four risk factors increased during the 10-year follow up period despite the high mortality among the group with many risk factors. CONCLUSIONS: The risk factor clusters among type 2 diabetic subjects are of great predictive value and when not aggressively treated, show a relentless increase despite selective mortality. PMID- 11213596 TI - Impaired glucose metabolism and obesity in Swedish patients with borderline isolated systolic hypertension: Skaraborg Hypertension and Diabetes Project. AB - AIM: To assess the prevalence of borderline isolated systolic hypertension (borderline ISH), and to examine its association with other cardiovascular risk factors. METHODS: A cross-sectional community-based study was carried out in 1993 1994 in Skara, Sweden, including 1109 randomly chosen subjects > or = 40 years old. Normotension (NT) was defined as systolic blood pressure (SBP) < 140 and diastolic blood pressure (DBP) < 90 mmHg, borderline ISH as SBP 140-159 and DBP < 90 mmHg and hypertension (HT) as SBP > or = 160 or DBP > or = 90 mmHg or ongoing treatment. RESULTS: The prevalence of borderline ISH (n = 203) by age was 4% in ages 40-49 years, 15% in ages 50-59 years, 28% in ages 60-69 years and 25% in ages 70-79 years. With borderline ISH as reference, normotensive subjects less often had fasting blood glucose > 5.5 mmol/l (odds ratio (OR): 0.4, 95% CI: 0.26 0.75), BMI > 27 kg/m2 (OR: 0.6, 95% confidence intervals (CI): 0.42-0.85) and known diabetes (OR: 0.4, 95% CI: 0.16-0.95). Hypertensive subjects more often had high density lipoprotein (HDL) cholesterol < 1.0 mmol/l (OR: 2.0, 95% CI: 1.35 2.99), a history of previous cardiovascular disease (CVD) (OR: 1.7, 95% CI: 1.01 2.72), known diabetes (OR: 2.4, 95% CI: 1.29-4.58) and microalbuminuria (men) (OR: 1.9, 95% CI: 1.15-3.11). CONCLUSION: Borderline ISH is a common condition. It is associated with a more unfavourable risk factor profile than that of normotensive subjects concerning primarily glucose metabolism and obesity. The prevalence of known diabetes increased with the degree of hypertension. PMID- 11213598 TI - Dyslipidaemia in African Americans, Hispanics and whites with type 2 diabetes mellitus and hypertension. AB - AIM: To study the pattern of dyslipidaemia in African American, Hispanic, and White patients with type 2 diabetes mellitus and/or hypertension. METHODS: The data were collected retrospectively on 6450 patients followed in the Harris County Hospital District Community Clinics. The information collected from review of the charts included each patient's age, sex, race, body mass index (b.m.i.), duration of type 2 diabetes mellitus and hypertension, medications, fasting plasma glucose, haemoglobin A1c, and fasting lipid profile. Mean lipid and haemoglobin A1c levels in the three ethnic groups were compared. The risk of abnormal cholesterol and triglyceride levels was assessed with logistic regression analysis. RESULTS: The results show that in patients with type 2 diabetes mellitus after correcting for age, sex and b.m.i., African Americans have the lowest serum triglyceride concentrations and Whites have the highest values. This trend holds true even in patients with hypertension and in patients with both hypertension and type 2 diabetes mellitus. The risk of having abnormal triglycerides is 74% lower in African Americans, and 42% lower in Hispanics than Whites based on logistic regression model. Despite better glycaemic control, Whites have a greater increase in serum triglyceride concentrations than Hispanics and African Americans. CONCLUSIONS: Although African Americans are known to be at higher risk for cardiovascular complications than Whites or Hispanics, they appear to have lower triglyceride concentrations than Whites or Hispanics in the presence of type 2 diabetes mellitus. This suggests that an increased prevalence of other adverse factors must contribute to their heightened cardiovascular risk. PMID- 11213597 TI - Effect of treatment with acarbose and insulin in patients with non-insulin dependent diabetes mellitus associated with non-alcoholic liver cirrhosis. AB - AIM: Non-insulin-dependent diabetes mellitus (type 2 diabetes) not responding to dietary treatment alone in patients with non-alcoholic liver cirrhosis is characterized by high postprandial hyperglycaemia. The control of postprandial hyperglycaemia in such patients, is generally achieved by the means of progressively higher doses of insulin, with an increasing risk of hypoglycaemia in the late postprandial period. The aim of this study was to evaluate the use of acarbose for the control of postprandial hyperglycaemia in 100 patients with well compensated liver cirrhosis and type 2 diabetes treated with insulin. METHODS: The study was double blind with randomization of treatments into acarbose (52 patients) vs. placebo (48 patients) with parallel branches over a period of 28 weeks. RESULTS: All patients tolerated the treatments well and no significant variations in liver function tests were observed (< 5% vs. pretreatment). A significant reduction of several parameters was observed only after acarbose treatment: fasting glycaemia (173 +/- 28 vs. 146 +/- 19 mg/dl; p < 0.01), postprandial glycaemia (230 +/- 24 vs. 148 +/- 20 mg/dl; p < 0.01), mean glycaemia (206 +/- 20 vs. 136 +/- 13 mg/dl; p < 0.01), mean variation (180 +/- 14 vs. 51 +/- 10 mg/dl; p < 0.01), HbA1c (8.9 +/- 0.8 vs. 7.2 +/- 0.5; p < 0.05), C peptide 2 h after a standard meal (4.5 +/- 1.9 vs. 2.8 +/- 1.7 ng/ml; p < 0.05), whereas the parameters did not change significantly after the placebo. After acarbose treatment a significant increase of intestinal voiding/week (+116% vs. +10%; p < 0.01) and a parallel reduction of blood ammonia levels (-52 +/- 9% vs. 9 +/- 5%; P < 0.01) were observed. CONCLUSIONS: The results clearly document the good tolerability and the absence of toxic effects of acarbose on liver, due to the lack of both intestinal absorption and hepatic metabolism of the drug at doses in the therapeutic range. In fact, acarbose increases the peristalsis movements of the gut, stimulates the proliferation of the saccarolytic bacteria and simultaneously reduces the proliferation of proteolytic bacteria, thus resulting active in the reduction of blood ammonia levels. These effects of acarbose may be advantageously exploited in the treatment of type 2 diabetic patients with well-compensated non-alcholic liver cirrhosis. PMID- 11213599 TI - Beta 3-adrenergic receptor gene polymorphism and type 2 diabetes in a Caucasian population. AB - AIM: The beta 3-adrenergic receptor (beta 3-AR) is suspected to play a key role in the regulation of energy balance by increasing lipolysis and thermogenesis. A mutation in the beta 3-AR gene (Trp64Arg) has been associated with the capacity of weight gain and with early onset of noninsulin dependent diabetes mellitus (type 2 diabetes). In this study we investigated the prevalence of the two beta 3 AR alleles in a Caucasian population and studied the association between the beta 3-AR genotype and metabolic disorders (obesity and type 2 diabetes). METHODS: Genomic DNA extracted from peripheral blood leucocytes of 200 Caucasian subjects (137 subjects with and 63 subjects without type 2 diabetes). The MvaI polymorphism of beta 3-AR, which detects the Trp64Arg mutation, was determined by polymerase chain reaction (PCR). We studied the correlation between the Trp64Arg mutation and the body mass index (b.m.i. kg/m2). RESULTS: There was no significant difference between the patients with type 2 diabetes and control subjects in the frequency of the Arg64 allele (5.5% and 4.8%, respectively). Within the group of type 2 diabetes patients were 14 subjects with the Trp64Arg mutation (b.m.i., mean +/- s.d.: 31 +/- 8.5 kg/m2) and 123 without the mutation (b.m.i. 29 +/- 4.8). There was no association between the beta 3-AR gene polymorphism and sex, obesity, blood pressure, glycohaemoglobin concentration, proteinuria. CONCLUSION: Our results suggest that the Trp64Arg mutation is not a major determinant of metabolic disorders (type 2 diabetes, obesity) and chronic complications of type 2 diabetes in a Dutch population. PMID- 11213600 TI - Recent developments and future prospects in pancreatic and islet transplantation. PMID- 11213602 TI - Spinal cord injuries. PMID- 11213603 TI - Latex-allergy concerns. PMID- 11213605 TI - Patient puzzle. Use systematic assessment to detect & correct patient conditions. AB - Medic 27 responds to a report of a fall victim at 27 West Pinnacle Lane. En route, the crew learns from dispatch that the patient fell approximately 25 feet from the roof of a three-story structure onto the roof of an adjacent garage. The caller reports the patient "going in and out of consciousness." The EMS crew requests the dispatch of a rescue unit and ladder company to assist on scene and the placement of a medical helicopter on standby. On scene, the patient's wife reports her husband accidentally disturbed a hornets' nest as he secured a weather vane to the top of the family home. She says the hornets stung her husband repeatedly. In his attempt to avoid the stings, his movements jarred the ladder, causing him to fall to the roof below. As you walk to the side of the patient's home, his wife adds that her husband has a cardiac condition and now complains of chest pain and trouble breathing. You wonder what you'll find when you reach the victim. Is he a medical patient with traumatic injuries or a trauma patient with medical complications? PMID- 11213604 TI - As the stomach turns.... PMID- 11213607 TI - JEMS 2001 resource directory. Need-to-know info at your fingertips. PMID- 11213606 TI - On the write track. 21 strategies to prepare clear & accurate documentation. PMID- 11213608 TI - HIPAA: where do providers stand? Roundtable discussion. PMID- 11213609 TI - PKI (public key infrastructure)--how and why it works. PMID- 11213610 TI - Beyond the buy-it button. PMID- 11213611 TI - Reducing medication errors. PMID- 11213612 TI - Making the leap to avoid medication errors. PMID- 11213613 TI - Mobile computing. PMID- 11213615 TI - Power plays and protection. PMID- 11213614 TI - Calling for a higher standard of service. PMID- 11213617 TI - ASPs (application service providers): a better tool. PMID- 11213616 TI - GIS technology helps pinpoint patients. PMID- 11213618 TI - What works. Calling all caregivers. PMID- 11213619 TI - What works. Documents on demand. PMID- 11213620 TI - Put a lock on security. PMID- 11213622 TI - Consultants hotlist. PMID- 11213621 TI - Backing up business. PMID- 11213623 TI - HIPAA to accelerate change in healthcare landscape. PMID- 11213624 TI - [Influence of tumor drug resistance phenotype on the dynamics of cisplatin induced changes of rat peripheral lymphocyte chromatin structure in Guerin's carcinoma]. AB - The correlation between the tumor drug sensitivity and the degree of lymphocyte interphase nuclei chromatin damages induced by cisplatin in rats was found using sensitive and resistant to cisplatin variants of Guerin's carcinoma. Increased optical density of lymphocyte chromatin in first minutes after cisplatin injection both in rats without Guerin's carcinoma and with sensitive to cisplatin variants of this tumor was observed. Lymphocyte chromatin structure remains unchanged in rats with cisplatin resistant carcinoma. Normal blood cells are suppose to change their sensitiveness to cisplatin under the humoral influence of the growing tumor in according with its phenotype. PMID- 11213626 TI - [Population genetics research in the Lerik region of Azerbaijan]. AB - The results of populational, clinic-genealogical and genetic-demographic research for six villages in Lerik region of Azerbaijan Republic are presented. The frequency of consanguineous marriages according to pedigrees was 62.3% with 32.4% of marriages between cousins. Inbreeding coefficient F = 0.0486 is considerably higher that the mean value for population of the Republic (F = 0.0063). The register of patients with congenital and inherited pathologies in the population of the studied villages has been set up. Genetic screening of glucose-6 phosphatedehydrogenase erythrocyte enzyme deficiency in schoolchildren revealed high frequency of pathologic gene (36.4%) previously unregistered for the population of the Republic. PMID- 11213625 TI - [Distribution of the 32 base pair deletion of the CCR5 chemokine receptor gene in different regions of Ukraine]. AB - The results of the analysis of 32 b.p. deletion in the CCR5 macrophage chemokine receptor gene in regional populations of Ukraine are presented. The frequency of this mutation ranged from 9.1% to 11% in the Slavs populations but in the population of Crimea Tartars the frequency of mutation was only 5%. PMID- 11213627 TI - [Comparison of the possibilities of micronuclear and chromosomal aberration tests for evaluation of the effects of radiation of different intensities]. AB - The comparative evaluation of sensitivity and specificity of the micronucleus and chromosome aberration tests for human lymphocytes at the delayed terms after acute exposure to high-dose as well as during constant exposure to low-dose gamma radiation has been done. Accordance between these tests registered only in the cases of acute radiation sickness of second and third degrees of severity (irradiation doses above 200 cGy). Unspecificity of micronucleus test for estimation of the radiation load under constant low-intensity irradiation was found. PMID- 11213628 TI - [Phylogeny of Finnish-Ugric populations]. AB - Genetic distances of 18 Finnish-Ugric and other populations of Europe, Asia and America by 28 alleles of 12 loci of proteins, enzymes and blood groups were calculated. The data of matrix of genetic distances and dendrogramme constructed by paired clusterisation method suggested that there was the relationship of Finnish-Ugric populations and some Caucasoids and North Mongoloid populations. These data give new approaches to the problem of Finnish-Ugric phylogenesis. PMID- 11213629 TI - [Creation of maize lines inducing maternal haploids with high frequency]. AB - The new inducers of maternal haploids have been created. The results on their inducing capacity in crossing with MK01u and A619 lines and MK01u x A619 hybrid are presented. Pollination with pollen of the new inducers allowed to obtain in average 6.5% of haploids among the three maternal genotypes. The ZMS and KMS initial lines induced 2.3% and 2.0% of haploids respectively. The frequency of haploids was studied in different parts of ears. It was found that in the higher part of an ear where the egg cells are the youngest during flowering the frequency of haploids was almost three times higher than in the lower part of an ear and more than twice higher than in the middle part of an ear. It was assumed that early pollination may increase frequency of obtaining haploids. PMID- 11213630 TI - [Development of Triticale and soft wheat forms with substituted wheat and rye chromosomes]. AB - During hybridization between winter forms of hexaploid (6x) triticale and soft wheat varieties the intergenomic substitution of alian chromosomes occurs. As a result of these crosses the forms of 6x-triticale with D(R)-substitution of chromosomes in R-rye genome by wheat ones of D-genome and wheat revertants with rye chromosomes replacing the wheat ones are originated. This is the simplest and the most effective technique for developing of selected lines of triticale and soft wheat with alien substituted chromosomes and valuable genes transfer. PMID- 11213631 TI - [Mutagenic effect of the herbicide Titus in maize]. AB - Mutagenic effect of the new herbicide titus has been studied by the tests of chromosome aberration and gene mutations in maize. It has been shown that the preparation in question possesses a definite mutagenic activity, which sometimes 5-7 times exceeded the level of spontaneous mutating. Therefore, when recommending it for application in agriculture it is necessary strict following recommended doses, because even slight excess may result in considerable genetic consequences. It is also of great importance to apply this herbicide during the recommended stage. The application of titus for maize in hybridization plots as well as in nurseries for reproduction of elite and super elite lines is not recommended. PMID- 11213632 TI - [Genetic diversity of isoenzymes in mountain pine (Pinus mugo Turra) in natural populations in the Ukrainian Carpathian mountains]. AB - Electrophoretic spectra of GOT, GDH, DIA, MDH, SOD, FDH, ADH, ACP, IDH enzymes in the megagametophytes of seeds of 69 mountain pine (Pinus mugo Turra) trees from natural populations of the Ukrainian Carpathian mountains have been described. 19 loci products had efficient electrophoretic separation. The analysis of alleles segregation of the heterozygous trees on the whole confirms monogenic inheritance of the discovered variants. PMID- 11213633 TI - [Morpho-functional characteristics of hemoglobinopathies]. AB - The approaches to the problems of primary diagnostics of the hereditary hematoglobinopathias caused by unbalanced synthesis of alpha and beta chains, as well as modern state of screening of hereditary thalassemic hematoglobinopathias are considered. The result of the available information analysis takes into account numerous peculiarities of this problem, including economic ones. Experience of an estimation of the displays of unbalanced synthesis of globin chains concerning the morphology of red blood cells is presented in the generalized form. The latter is a very important for preliminary diagnostics the hematoglobinopathias because, for the first, it may be realized at primary units of public health system service, for the second, it allows to narrow to an acceptable level the group of persons whose blood requires more complex and expensive researches. PMID- 11213634 TI - [Structure and function of thyroid hormone receptors]. AB - The new data concerning the structure of nuclear receptor of thyroid hormone and peculiarities of its functioning as a ligand-dependent transcriptional factor are reviewed. Considerable attention is concentrated on the analysis of mechanisms of receptor interactions with specifical DNA regions which mediate iodothyronine influence on the gene expression and factors that participate in regulation of these mechanisms. PMID- 11213635 TI - Physician practices. Slowing the flow of red ink. PMID- 11213636 TI - Nurse shortage. An eBay for RNs. PMID- 11213637 TI - Suicide prevention. Death-defying acts. PMID- 11213638 TI - Medical schools. Changing course. PMID- 11213639 TI - Hopkins HealthCare. Home-grown TPAs. PMID- 11213641 TI - Back to basics. PMID- 11213642 TI - Wired & waiting. AB - Disease management was supposed to be the next big thing in health care, thanks largely to the breathtaking pace of advances in technology. But so far reports of a disease management revolution have been premature. While technology vendors promise that their devices can save millions and keep patients healthier longer, providers have been reluctant to make the large investments necessary until they have proof of a payoff. Formal studies and reliable statistics to provide such proof are sorely lacking, although anecdotal evidence appears to signal high hopes for the future. PMID- 11213644 TI - Short supply. PMID- 11213645 TI - [Organ donation, retrieval, and transplantation in Italy, in 1994-98]. AB - Organ donation and transplantation activity in Italy have been always characterised by two contrasting features: first the constant positive trend in the improvement of the number of organ donors and transplants which allowed the country to exceed the value of 12 donors per million population in 1998; second the difficult situation in southern regions, so that the national distribution of the activity is highly and steadily non homogeneous. Herein we report the data regarding donation, retrievals and transplant activity in Italy in the years 1994 98, focusing on the activity of each region and the three interregional centres which encompass the majority of the national territory. PMID- 11213646 TI - [Organ transplantation: results and perspectives]. AB - Nowadays organ transplantation is a life-saving procedure, or anyhow it can considerably improve the life quality of patients suffering from irreversible organ impairment. Monitoring transplantation outcome is the last step of a long process that starts with cadaver donor identification, selection and clinical management, and continues with organ allocation, patient evaluation, surgical operation and clinical follow-up. The National Transplantation Committee has been discussing many of these items and, in 1995, it set up two protocols, one on liver exchange for urgent patients and the other on transplantation in the pediatric patient. The protocols application has met many difficulties, mainly due to the uneven behaviours of the different inter-regional organizations. In this paper we comment on the two main aspects to be submitted to the next National Committee: organ allocation and transplantation outcome. As far as the last point is concerned, the enclosed data are based on the experience of the North Italy Transplant program (NITp), and on that of the major international registries. Without any doubt these data demontrate that organ transplantation is to be ascribed among the successes of medicine in the just closed century. PMID- 11213647 TI - [Transplantation collaborative networks]. AB - The collaborative networks in Italy are described, with their objectives and the geographical areas covered. Their main features are: function of the reference centres, waiting lists, criteria for organ assignment, common programmes for some patients, services offered to the network members, organ procurement activity. The analysis of the activities performed included organ exchanges within and outside the network, common activities for tasks that could not be satisfactorily attained by a single centre or region, the collaborative studies. Finally, the role of the networks and of a national coordination, in order to better develop transplants nationwide, is discussed. PMID- 11213648 TI - [Planning of transplantation centers]. AB - Health policies are correlated with the economics resources invested in each specific field. The planning of organ transplant centres depends on the relationship between health demand and health offer. The health demand is due to the number of the patients which are waiting for a transplant, while the health offer is represented by all the specific resources: number of cadaver donors and transplant centres. The analysis of transplant activity performed in Italy during the period 1996-1998 suggests that it is not necessary to increase the number of transplant centres but that of organ donors. PMID- 11213649 TI - [Tissue-typing laboratories for organ transplantation]. AB - The tissue typing laboratory performs genetic analysis: the safety and the reproducibility of results are mandatory, because HLA typing can be crucial both in donor-recipient compatibility assessment for organ transplantation and for the diagnosis of immune related disease. The HLA laboratory should perform analysis, as quickly as possible, in order to define donor-recipient matching and to assess the presence of anti-donor specific antibodies in recipient's serum to prevent iperacute rejection. The aim of this report is to define the guidelines that should be followed in all laboratories for each specific transplantation in order to acquire national and international accreditation, and to obtain the best clinical results. PMID- 11213650 TI - [Statistical bases and models for the selection of kidney transplant recipients]. AB - The thesis of this study is that the use of discrete simulations is the most appropriate instrument to support the definition of a kidney allocation procedure. We first furnished a general description of what it means to run a simulation to solve the problems related to the study of the statistical characteristics of any population. In the second part of the paper we mathematically formalized the subject of our study: the statistical properties of waiting lists, allocation algorithm and transplants. The third part reported the results of several simulations we have done with the aim to show the potential of these methods at assessing the most appropriate adjustments for the optimization of any allocation scheme. PMID- 11213652 TI - [Italian patients who received transplants from foreign countries]. AB - The article analyzes the procedures for patient transferal to foreign countries presently adopted in Italy, with a particular insight in organ transplantation. All the legal and sanitary regulations that, from 1970 on, have regulated this issue for the European Community (now European Community) and extracommunitary countries are reviewed. The present legislation is reported and the guidelines for transferal to foreign countries is illustrated. The role of the specialistic regional referral centers in the concession of the authorization is examined in detail. The few available official sources have been reviewed to illustrate the migratory fluxes of transplant candidates in the recent years. Finally, the procedures that could make the system more efficient and uniform on the whole territory are reported. PMID- 11213651 TI - [The national program of pediatric transplantation]. AB - The national programme for paediatric transplants currently implemented at the Istituto Superiore di Sanita is one of the first results of the efforts devoted to the definition of an efficient co-ordination policy of the transplantation activity in Italy. Since 1997 the programme has allowed all transplant centres throughout Italy to share unified waiting lists for kidney, heart, lung and liver, which gives paediatric patients a much better possibility than with local waiting lists. We present the regulations, criteria and operative solutions adopted to make the programme work, and the analysis of the data collected in these three years. The analysis gives statistical information on the composition and evolution of waiting lists and transplants done, which may be useful in the continuous process of revision and improvement of the criteria for recipient selection. PMID- 11213653 TI - [Waiting lists for transplantation in Italy]. AB - To plan health services it is essential to gauge the needs. In transplant field in Italy, the first suitable data for waiting lists were collected in 1998. The data collected by Istituto Superiore di Sanita gave us a shot of patients field in waiting list at that time. We here analyse more significant data about heart, liver and kidney waiting lists. The situation is very different among north, centre and south of Italy: in South, where transplant activity is low, we found rare transplant centres, and most of patients prefer north centres. In kidney waiting list we found 1100 patients living in southern regions but registered in the waiting list of a different region. These data can help in planning development lines in Italy. PMID- 11213654 TI - [Psychological assistance in organ transplantation]. AB - The aim of this report is introducing with a series of psychological, psychiatric and psychosocial problems, that can arise, at every point, in the procedure of organ transplantations. Different areas of intervention are considered: the assistance to the patients and their families during the pre- and post-operative periods; the evaluation of transplant recipients' quality of life; ethical and psychological problems of living kidney donation; psychosocial support to donors' families; the training of the intensive therapy units to entertain relationships with donors' relatives; the delicate psychological aspects of transplantation during childhood. The sense of awareness about these matters is growing in Italy too, and many initiatives of psychological and psychiatric help are being developed in collaboration with several transplantation centres. PMID- 11213655 TI - [The transplant coordinator]. AB - Spain was the first European country adopting a strategy of organ procurement based on a specific health professional named transplant coordinator, who was first established in Catalunya in the middle eighties. In principle, the transplant coordinator is a doctor with hospital experience who is involved full time in organ procurement. The transplant coordination activity is available without interruption, due to a team work. Transplant coordination is based on four main functions: clinical, research, training and communication, management. The principles of transplant coordination according to the Spanish model are reported in the recently approved Italian law on transplantation (law 91/1999), indicating the coordinator's specific functions: a) communication to the regional reference centre of the data concerning the possible organ donors, b) preparation of the documents needed, c) relationship with the donors' family, d) information and education of the population on transplantation issues. PMID- 11213656 TI - Endoscopic retrograde cholangiopancreatography: what role does it have in primary care? AB - Endoscopic retrograde cholangiopancreatography (ERCP) is a unique specialty tool used for the diagnosis and treatment of biliary and pancreatic disease. The procedure is much more available now and can be used in place of surgery or in conjunction with surgery. This article reviews the indications, applications, and personal experiences with the procedure in a rural referral hospital. Discussion includes the risks and complications of ERCP. Also included are explanations of therapeutic interventions. After reading this article, primary care physicians should have greater familiarity with the utility of this endoscopic tool. PMID- 11213657 TI - A primary care approach to pediatric gastroesophageal reflux. AB - Gastroesophageal reflux is a common problem that occurs in the pediatric population. Gastroesophageal reflux refers to the retrograde passage of gastric contents into the esophagus. Current thinking implicates transient lower esophageal sphincter relaxations as a major cause for reflux. Infants generally present with symptoms of regurgitation, whereas symptoms of esophagitis are more common in older children. When there are dangerous consequences secondary to gastroesophageal reflux, it is termed gastroesophageal reflux disease (GERD). GERD has been shown to manifest with respiratory symptoms and a pathologic process. A variety of diagnostic procedures are available for the assessment of GERD which include barium swallow, pH probe, scintigraphy, and endoscopy with esophageal biopsy. Medical management of GERD primarily involves prokinetic agents and acid suppression therapy. Surgical therapy, albeit less common, now still has its role in the treatment of GERD. PMID- 11213658 TI - Acute gastrointestinal bleeding: clinical essentials for the initial evaluation and risk assessment by the primary care physician. AB - Acute gastrointestinal bleeding is a common medical emergency that frequently results in hospitalization. Rapid initial assessment of clinical parameters such as estimated volume of blood lost, appearance of expelled blood, hypotension, mental status changes, and coagulopathy should all be evaluated as part of the outcomes prediction equation. For upper gastrointestinal bleeding, early endoscopy of the upper gastrointestinal tract will also provide important information to aid in efforts to predict risk. Endoscopic evidence of ongoing rapid bleeding or the presence of a "visible vessel" or adherent clot on the ulcer base are findings that are associated with a high likelihood of continued bleeding or recurrent bleeding. Endoscopic therapy can reduce the rates of recurrent bleeding, surgery, and length of hospital stay in patient with these "stigmata of recent bleeding." Other endoscopic ulcer appearances such as brown or black pigment in the ulcer base or a clean ulcer base do not require endoscopic therapy, as rates of recurrent bleeding are very low for these lesions. Use of these clinical and endoscopic outcome predictors can also be useful in refining triage decisions as to which patients need to be in the intensive care unit, which need to be admitted to the hospital, and which can have early oral feeding and expedited hospital discharge or outpatient care. PMID- 11213659 TI - Sleep-related gastroesophageal reflux. AB - Although we spend approximately one third of our lives sleeping, rarely do we consider that sleep may contribute to medical conditions. For gastroesophageal reflux, sleep or physiologic changes associated with the sleep state often promote or increase the likelihood of reflux and aspiration. These changes include the assumption of the supine position, a decrease in the arousal threshold, mechanical effects of the abdomen, and disorders associated with sleep. Of the sleep disorders, obstructive sleep apnea is associated with a high frequency of gastroesophageal reflux, probably due to the generation of negative intrathoracic pressures and obesity associated with the disease. Obstructive sleep apnea in patients with gastroesophageal reflux can lead to difficult-to treat or refractory gastroesophageal reflux, predominantly nocturnal or early morning symptoms, and unusual or uncommon manifestations that do not appear to reflect the underlying pathologic process. Under most circumstances, aggressive treatment regimens must be instituted for both disorders in order to effectively control symptoms. This article reviews the major information that is currently available on the relationship between obstructive sleep apnea and gastroesophageal reflux. PMID- 11213660 TI - Fair hearing/peer review: truth or oxymoron? PMID- 11213661 TI - Time for Medicare reform is now. PMID- 11213662 TI - Questioning of OCF should rouse osteopathic response. PMID- 11213663 TI - Hardship deferment saves residents' money. PMID- 11213664 TI - Spirituality in medicine. PMID- 11213666 TI - Minor depression in primary care. AB - Minor depression is defined as a mood disturbance of at least 2 weeks' duration, with between two and five symptoms of depression, including depressed mood, diminished interest, weight change, sleep disturbance, psychomotor changes, fatigue, feelings of worthlessness, poor concentration, and recurrent thoughts of death. Patients with this condition may have fewer vegetative symptoms (appetite, diurnal mood variation) and more subjective symptoms (self-blame, worry, irritability, lethargy). Minor depressive disorder is more prevalent in primary care than major depressive disorder. Failure to adequately treat this condition may have far-reaching impact on the health, functional status, quality of life, and cost of care for patients who have it. The notion that minor depression requires minor treatment is misleading. Cognitive-behavioral modes of therapy and selective serotonin reuptake inhibitor antidepressants have demonstrated efficacy for primary care patients who have minor depression. PMID- 11213665 TI - Benefits of osteopathic manipulative treatment for hospitalized elderly patients with pneumonia. AB - While osteopathic manipulative treatment (OMT) is thought to be beneficial for patients with pneumonia, there have been few clinical trials--especially in the elderly. The authors' pilot study suggested that duration of intravenous antibiotic use and length of hospital stay were promising measures of outcome. Therefore, a larger randomized controlled study was conducted. Elderly patients hospitalized with acute pneumonia were recruited and randomly placed into two groups: 28 in the treatment group and 30 in the control group. The treatment group received a standardized OMT protocol, while the control group received a light touch protocol. There was no statistical difference between groups for age, sex, or simplified acute physiology scores. The treatment group had a significantly shorter duration of intravenous antibiotic treatment and a shorter hospital stay. PMID- 11213667 TI - Re-expansion pulmonary edema following puncture of a giant bulla. AB - Ipsilateral pulmonary edema may occur in a lung that has been rapidly reinflated after a period of collapse. The syndrome of re-expansion pulmonary edema is associated with variable degrees of hypotension and hypoxemia. In its extreme form, it may result in cardiac arrest and death. The initial cause of uninflated pulmonary parenchyma described with re-expansion pulmonary edema has typically been either a large undrained pleural effusion or a pneumothorax. The authors describe a patient in whom re-expansion pulmonary edema developed when inadvertent puncture of large emphysematous bullae released previously atelectatic lung. PMID- 11213668 TI - Collaboration between pharmacy and osteopathic medicine to teach via the Internet. AB - This article describes the results of a survey from graduate pharmacy students who completed a neurology/psychiatry course taught by a pharmacist and an osteopathic physician via the Internet. Seventeen practicing pharmacists completed the 11-week course, and thirteen students completed the survey provided at the end of the course. Results indicated that students were pleased with the course. Mean evaluation scores ranged from 4.31 to 4.77 on a five-point scale. Additionally, students indicated that the collaboration of medicine and pharmacy provided an educational model that should be duplicated for future courses. PMID- 11213669 TI - Government control of medicine. PMID- 11213670 TI - Plasma exchange in myasthenia gravis and multiple sclerosis. AB - During the last twenty-year period therapeutic plasma exchange (TPE) was used in the treatment of 68 patients with myasthenia gravis and 61 patients with multiple sclerosis. The therapeutic effects were evaluated on the basis of neurologic deficit changes, electrophysiological findings, necessary laboratory analyses and patient's general conditions. It was shown that the therapeutic effects mosty depended on the nature and stage of the basic disease, adequate selection of the patients and timely applied therapeutic procedure. Significant positive effects of the TPE treatment applied with the anti-inflammatory and immunosuppressive therapy were observed in patients with myasthenia gravis and multiple sclerosis upon clinical findings and some paraclinical tests. PMID- 11213671 TI - [Blood transfusion therapy at the Military Medicine Academy--present possibilities]. AB - Blood component therapy refers to the transfusion of the specific part of blood that a patient needs, as opposed to the routine transfusion of whole blood (WB) in the past. This not only maintains blood resources, but also provides the optimal method of transfusing patients who require large amounts of a specific blood component. Since this concept have been accepted, the Institute of Transfusiology of Military Medical Academy (MMA) possess appropriate equipment for blood collection and processing of WB in components. Mainly, all kind (except frozen) of packed red cells (RBCs), platelet concentrates (random-donor buffy coat or apheresis donation), single-donor (apheresis) or random-donor (buffy coats) granulocytes, fresh frozen plasma (FFP), single-donor cryoprecipitate are prepared. Recently, fibrin glue (obtained by recycled cryoprecipitation from single-donor or autologous plasma), and some of new generation of blood components: hematopoietic stem and progenitor cells (fresh or cryopreserved), collected from bone marrow or harvested from peripheral blood after mobilization and donor-specific mononuclear cells for cell therapy, i.e. immunomodulation during relapse of leukemia after bone marrow transplantation, have become the routine. Analysis of blood component therapy done at the MMA during the past 11 years (1989-1999) showed that: a) participation of WB transfusion in the group of surgical clinics was permanently decreased (from 59.60% in 1989 to 0.37% in 1999); b) WB transfusion (in the last few years) practically was not used in the group of internal medicine clinics (0.82% in 1993 and 0.45% in 1999); c) overall WB transfusion in MMA is extremely rare (0.37%). PMID- 11213672 TI - [Biochemical changes in thrombocyte concentrates stored for 5 days]. AB - The purpose was to evaluate biochemical and functional changes in platelet concentrates prepared from buffy-coat (PC-BC), stored up to five days at temperature of 20 +/- 2 degrees C. Forty-two PC-BC units from random blood donors were examined. In order to determine the biochemical changes we studied the release of lactate dehidrogenase (LDH), changes in pH value, pCO2, pO2, glucose and lactate concentrations. In addition, the aggregation of platelets with adenosine diphosphate (ADP), and hypotonic shock response were examined. The concentration of LDH markedly increased from 138.8 IU/l (day 1st) up to 234 IU/l (day 5th). The lactate concentration increased significantly (p < 0.001) from 2.1 to 8.6 mmol/l, and consequently pH decrease was observed (from 7.31 to 7.13). The level of glucose decreased gradually from 22.8 to 19.4 mmol/l. The pCO2 decreased progressively from 36.8 mmHg to 24 mmHg during first two days of storage and after that gradually to 20 mmHg. In contrast, pO2 fluctuated between 108 and 133 mmHg during five day of storage. Recovery of hypotonic shock response was 70% on day 1st and 35.7% on day 5th, respectively (p < 0.001). Platelet aggregation using ADP showed significant increase from 6.6 sec (day 1st), to 11.2 sec (day 4th) and 14.6 sec (day 5th), too. Significant differences in biochemical parameters and platelet functions, with confirmed relationship between changes obtained during five days stored PC-BC did not affect the efficacy of applied platelets. PMID- 11213674 TI - [Advantages of polyethylene glycol in comparison to bovine serum albumin in the indirect antiglobulin test in pregnant women]. AB - Results of indirect antiglobulin test (IAT) adding polyethylene glycol (PEG) were compared with conventional IAT performed using bovine serume albumin (BSA) with the aim of prenatal protection of Rh(D) negative pregnant women. Investigation enrolled 986 samples of pregnant women sera and confirmed that the use of PEG-IAT increased the degree of detection of clinically significant antierythrocyte antibodies. Above all, form the Rhesus blood groups system (using exclusively PEG IAT) was detected by one antibody of anti-D, anti-C, anti-e and two anti-E), while by using BSA, anti-e was not detected at all. Besides, the need for additional serologic techniques has been reduced (treating of erythrocytes by enzymes) and the work of laboratories for prenatal protection has been alleviated, and at the same time the quality of analyses was not diminished, which gave the preference to PEG-IAT compared to BSA-IAT in prenatal testing. PMID- 11213673 TI - [Significance of blood transfusion in the development of cytotoxic antibodies in patients on hemodialysis]. AB - The aim was to evaluate the influence of red blood cells (RBC) transfusion on the development of cytotoxic antibodies (C-Ab) in patients subjected to hemodialyses (HD) and planned for the kidney transplantation. The group of 71 HD patients, of mean age 42 years (19-65), 48 males and 23 females, planned for the kidney information was examined. Out of 71 HD patients, only 42 (59.19%) HD patients (group I) received subcutaneously recombinant human erythropoietin--rhuEPO (Eprex -epoetin-alpha or Recormon SE--epoetin-beta in dosage of 4,000 IU during every HD; i.e. one to three times a week) and they were not treated by RBC transfusion. The other 29 (40.85%) HD patients (group II) received RBC transfusion: 18 (62.07%) HD patients received < 10 units 18 of RBC, 8 (27.59%) HD patients received 10-20 units of RBC; 3 (10.35%) HD patients received > 20 units of RBC. Testing of C-Ab was done in all patients every three months by standard lymphocytotoxicity test on the panel from 20 different lymphocyte donors with definite class I phenotype of antigen HLA. C-Ab was not found in HD patients who were not treated by RBC transfusion. Out of 18 HD patients who received < 10 units of RBC only 3 (16.67%) HD patients developed C-Ab; out of 8 HD patients who received 10-20 units of RBC, in 4 (50%) patients was proved C-Ab; and C-Ab was proved in all 3 HD patients who received > 20 units of RBC. RhuEPO administration is very important for the transfusiologic treatment of HD patients; especially those who are planned for the kidney transplantation. Development of C-Ab is in direct correlation with the number of transfunded units of RBC. HD patients who received 10 or more units of RBC were at great risk to develop C-Ab. PMID- 11213675 TI - [Detection of anti-HCV antibodies in patients on long-term hemodialysis]. AB - Hepatitis C virus (HCV) infection is highly prevalent among chronic dialysis patients and is the most common cause of chronic liver disease. Ninety six patients on chronic hemodialysis in our institute of transfusiology at the Military Medical Academy were evaluated for the presence of HCV infection. There was a significant relationship between presence of anti-HCV antibodies and number of blood transfusion received by examined patients. We concluded that hepatitis C is a common problem among patients on chronic hemodialysis in our institution: HCV infection is proved in about 48.95% of all patients on hemodialysis. PMID- 11213676 TI - [Aspects of transfusion-infusion therapy during war conditions]. PMID- 11213677 TI - [Treatment of Hodgkin's disease with high-dose chemotherapy and autologous stem cell transplantation]. AB - High dose chemotherapy (HDC) with autologous stem cell transplantation (SCT) was applied for the treatment of 13 patients (pts) with Hodgkin's disease (HD) (10 with relapsed form and 3 with conventional chemotherapy resistant form) in the Clinic for Hematology, Military Medical Academy, from May 1997 to October 1999. After the initial treatment for the reduction of tumor, burden stem cells were mobilized by cyclophosphamide 2.5-7.0 g/m2 with G-CSF 5-12 micrograms/kg body mass (BM). The average number of colected mobilized mononuclear cells (MNC) was 2.99 (1.66-5.9) x 10(8)/kg BM by the apheresis large volume from peripheral blood. All patients received BEAM (BCNU, etoposide, Cyto-Ara, and melfalan) conditioning regimen with adequate supportive therapy. Good engraftment (100%) was observed at postransplantation period: number of polymorphonuclear cells was > 0.5 x 10(9)/l, on day 13th (10-21) and number of platelets > 20 x 10(9)/l, on day 17th (11-28). One patient (7.6%) died due to infective complications at day 98th after transplantation, 9 (69.2%) patients achieved complete and 3 (23.1%) patients partial remission of the disease. Out of three patients with partial remission, one relapsed, seven months after autologous SCT, with conventional chemotherapy resistant form and two, after the applied conventional locoregional radiotherapy reached remission. One patient (7.6%) developed secondary malignancy of acute myeloid leukemia form with threelinage displasy 27 months after autologous SCT. HDC with autologous SCT contributes to more successful treatment of early relapsed and standard chemotherapy resistant forms of HD and gives the opportunity for successful quality of living for those patients. PMID- 11213678 TI - [Cytomegalovirus infection in patients with kidney diseases]. AB - Cytomegalovirus (CMV) has a prominent position as the cause of severe cytomegalovirus infection (CMVI) in immunocompromised persons, such as: patients with primary or secondary immunodeficiency (risk group), blood/hemoproducts recipients, especially recipients of tissue and organ transplants, which have implications for difficult providing of CMV-seronegative (safe) blood. However, CMV-disease is manifested in the minority of immunocompetent persons. Sera of patients from the Center for Hemodialysis of the Clinic of Nephrology of the Military Medical Academy (MMA) were tested on the presence of CMVI markers. All patients belonged to the risk group considering the chronicity of the main disease, receiving of the large quantities of blood and as the possible potential recipients of kidney transplants. Testing was performed by commercial serologic enzyme-immune tests (Abott--USA, Behring--Germany) for CMV antibodies of IgG and IgM classes by which was determined serologic state of patients. Test results: out of 106 tested sera samples, 100 (99.33%) were CMV-seropositive (CMV-IgG), 27 (25.47%) were positive on recent CMVI (CMV-IgM), 99 (93.39%) received the blood previously, the majority of patients were with the diagnosis of primary glomerulopathy--68 (64.15%) and tubulointerstitial nephropathy--32 (30.18). Such results indicate the potentional possibility of reactivation of latent CMV and development of CMVI, and in transplant recipients--its rejection. It can occur if appropriate measures of prevention from CMVI are not timely undertaken, which includes the providing of CMV-seronegative-safe blood/hemoproducts, as well as the appropriate application of combined medicamentous therapy by chemical agents and immunomodulators-specific hyperimmune anti-CMV immunoglobulins. PMID- 11213679 TI - [Therapeutic use of blood products and their recombinant analogs in patients with disorders of hemostasis]. PMID- 11213680 TI - [Flow cytometry in quality control of the new generation of blood products prepared for use in stem cell transplantation]. PMID- 11213681 TI - Donor leukocyte infusion--the effect of mutual reactivity of donor's and recipient's peripheral blood mononuclear cells on hematopoietic progenitor cells growth. AB - Donor leukocyte infusions are an effective therapy for patients who relapse with leukemia after bone marrow transplantation. We report the case of 14-year-old boy who relapsed 34 months after sibling donor bone marrow transplant for Philadelphia-positive chronic myeloid leukemia. Subsequently, he received three infusions of donor mononuclear cells (DMNC) harvested in steady state hematopoiesis and one G-CSF mobilized-peripheral blood mononuclear cells (PBMC) infusion. Simultaneously, test named as--"Test of Mixed Progenitors" (TMP) was performed for the assessment whether the outcome of donor leukocyte infusion treatment could be predicted. Prior to DMNC infusions, the CFU-GM and BFU-E colony assays were performed for donor's and recipient's PBMC individually, as well as for the mixture of these cells at 1:1 ratio. The cells were plated either directly in the semisolid medium or after 24 h preincubation treatment. Significantly lower values for CFU-GM derived colonies were determined in TMP in comparison to the CFU-GM values obtained for the recipient's cells. The reduced number of CFU-GM was determined both in TMP performed without preincubation treatment, app. 80% and after the 24 h preincubation, app. 55%. The reduced number of BFU-E derived colonies (app. 44%) was observed only related to recipient's cells and after the preincubation treatment of the cells. The patient did not develop GVHD and currently (40 months after the first infusion). He remained well in complete hematological, cytogenetic, molecular and clinical remission, which was the most direct evidence of the GVL effect. The novel in vitro TMP test in which the specific contribution of donor's leukocytes to the growth of recipient's hematopoietic precursor cell growth was determined, correlated with the clinical outcome. PMID- 11213682 TI - [Second allogenic bone marrow transplantation after late graft rejection in a patient with severe aplastic anemia]. AB - Allogeneic bone marrow transplantation (BMT) is the treatment of choice in young patients (pts) with severe aplastic anemia (SAA) who have an HLA identical sibling donor. Late graft rejection to following allogeneic BMT for SAA is a significant clinical problem and is associated with a high risk of mortality. The optimal treatment strategy for patients with late graft rejection after first BMT is still an open question. We report 12-year-old patient with acquired SAA who underwent BMT from his HLA identical sister. BMT was first-line treatment within 3 months of diagnosis. Preparative therapy was Cyclophosphamide (Cy) 200 mg/kg body mass (BM) during 4 days. Graft versus host disease (GVHD) was prevented with Methotrexate (MTX), Methylprednisolone (MPDN) and Cyclosporin A (CsA). After 17 months, during which patient was with normal blood counts and full donor chimaerism, graft rejection occurred. The patient was re-engrafted from the same donor after conditioning with Cy 200 mg/kg BM plus horse antithymocyte globulin (ATG)--2 vials (a 25 mg)/10 kg BM over 4 days. Before the collection, donor's bone marrow was activated with low dose rhGM-CSF (3 micrograms/kg one day). Following a secondary BMT engraftment has sustained. The patient is alive with full donor chimaerism 26 months from secondary transplantation, without acute or chronic GVHD. PMID- 11213683 TI - [Secondary myelodysplastic syndrome after autologous transplantation of hematopoietic stem cells in a female patient with Hodgkin's disease]. AB - Secondary acute myeloid leukemia with threelineage displasy (sAML/MDS) has been described as a complication of therapeutic approach with high-dose chemotherapy and autologous stem cell transplantation (SCT) in the patients with Hodgkin's disease (HD). It is not yet clear whether the sAML/MDS is a consequence of a standard therapeutic regimen, applied before transplantation, or a high-dose chemotherapy. In a female patient with initially resistant form of HD at III-B-b clinical stadium (bulky disease in neck and mediastinum) after the initial treatment (MOPPx4; ABVDx3; BEA-COPPx2), high-dose chemotherapy has been applied according to BEAM protocol with autologous SCT. In a period after transplantation, radiotherapy (RT) has been applied at initial region of the disease and a patient reached complete remission (CR), which lasted for a 27 months. After that period sAML/MDS has been observed. Application of more standard therapeutic cycles and characteristic cytogenetic findings are the facts that support the opinion that sAML/MDS is a consequence of standard treatment before transplantation, rather than high-dose chemotherapy. That finding implies the need for correct choice of the HD patients suitable for early SCT therapeutic approach. PMID- 11213684 TI - Managing in the whitespace. AB - The assumption today is that new value in a company can be created only when people shed their suits, don khakis and Hawaiian shirts, and think and act like the most passionate entrepreneurs. The problem is, they're rarely told when it makes sense to do those things--or how to do them. With help from a team of ethnographers and senior organization specialists, authors Mark Maletz and Nitin Nohria recently conducted a unique research project that attempted to full those gaps. Their project focused on whitespace: the large but mostly unoccupied territory in every company where rules are vague, authority is fuzzy, budgets are nonexistent, and strategy is unclear--and where entrepreneurial activity that helps reinvent and renew an organization most often takes place. The researchers shadowed entrepreneurial managers operating in the whitespace and met with top managers about their efforts to oversee whitespace activities. Using examples from the financial services, computer, and e-commerce industries, the authors explain when it's imperative to operate in the whitespace--and when it's wiser to stay in the traditional blackspace. They describe how effective whitespace managers subtly and resourcefully lead successful efforts, and how senior executives nurture whitespace projects by putting aside their traditional planning, organizing, and controlling techniques. Finally, they examine the ultimate issue for any successful whitespace project: should it be moved into the blackspace, kept in the whitespace indefinitely--or, despite its apparent success, killed off? If companies leave this valuable territory to the scattershot whims and talents of individual managers, the authors say, they are likely to miss out on many of the opportunities that come from exploring the next frontier. PMID- 11213685 TI - The business against case revolution. An interview with Nestle's Peter Brabeck. Interview by Sue Wetlaufer. AB - One of the world's most enduring companies, Nestle epitomizes everything that today's high-flying, headline-grabbing companies are not. It respects technology but doesn't consider it central to strategy. It values growth but prefers it controlled. It seeks talented professionals but wants only those who are modest in word and deed. Nestle CEO Peter Brabeck is skeptical of the relentless push for radical transformation heard from every quarter. He believes, instead, in continuous improvement through slow and steady change. Big, dramatic change is fine for a crisis, Brabeck says, but not every company is in crisis all the time. Many companies are like Nestle--performing well, growing and innovating, without frenzy, without bloodshed. While he acknowledges that every company must change in order to compete in today's turbulent marketplace, Brabeck makes the focus of his work identifying and strengthening those aspects of Nestle that should stay the same. For example, Nestle eschews the noise and energy swirling around technology. Many companies make technology the focal point of strategy, Brabeck says, but Nestle is about people, products, and brands. The company uses technology to create better products but keeps it in its right place--the background. Brabeck also talks candidly about how to fight complacency in a successful company, how to institutionalize collaboration in a decentralized organization, and how to resist pressure from analysts and money managers and focus on long-term, sustainable and profitable growth--in short, how to win the war without the revolution. PMID- 11213686 TI - Price smarter on the Net. AB - Companies generally have set prices on the Internet in two ways. Many start-ups have offered untenably low prices in a rush to capture first-mover advantage. Many incumbents have simply charged the same prices on-line as they do off-line. Either way, companies are missing a big opportunity. The fundamental value of the Internet lies not in lowering prices or making them consistent but in optimizing them. After all, if it's easy for customers to compare prices on the Internet, it's also easy for companies to track customers' behavior and adjust prices accordingly. The Net lets companies optimize prices in three ways. First, it lets them set and announce prices with greater precision. Different prices can be tested easily, and customers' responses can be collected instantly. Companies can set the most profitable prices, and they can tap into previously hidden customer demand. Second, because it's so easy to change prices on the Internet, companies can adjust prices in response to even small fluctuations in market conditions, customer demand, or competitors' behavior. Third, companies can use the clickstream data and purchase histories that it collects through the Internet to segment customers quickly. Then it can offer segment-specific prices or promotions immediately. By taking full advantage of the unique possibilities afforded by the Internet to set prices with precision, adapt to changing circumstances quickly, and segment customers accurately, companies can get their pricing right. It's one of the ultimate drivers of e-business success. PMID- 11213687 TI - Are the strategic stars aligned for your corporate brand? AB - In recent years, companies have increasingly seen the benefits of creating a corporate brand. Rather than spend marketing dollars on branding individual products, giants like Disney and Microsoft promote a single umbrella image that casts one glow over all their products. A company must align three interdependent elements--call them strategic stars--to create a strong corporate brand: vision, culture, and image. Aligning the stars takes concentrated managerial skill and will, the authors say, because each element is driven by a different constituency: management, employees, or stakeholders. To effectively build a corporate brand, executives must identify where their strategic stars fall out of line. The authors offer a series of diagnostic questions designed to reveal misalignments in corporate vision, culture, and image. The first set of questions looks for gaps between vision and culture; for example, when management establishes a vision that is too ambitious for the organization to implement. The second set addresses culture and image, uncovering possible gaps between the attitudes of employees and the perceptions of the outside world. The last set of questions explores the vision-image gap--is management taking the company in a direction that its stake-holders support? The authors discuss the benefits of a corporate brand, such as reducing marketing costs and building a sense of community among customers. But they also point to cases in which a corporate brand doesn't make sense--for instance, if you are a product incubator, if you've recently experienced M&A activity, or if you are expecting fallout from risky ventures. PMID- 11213688 TI - Retention through redemption. AB - Corporate America and the U.S. Navy share one big problem: employee retention. Today's knowledge workers hop from start-up to start-up. And 40% of the navy's new recruits leave the service before their four-year tours of duty are up. D. Michael Abrashoff came face to face with the navy's retention problem when he took command of the USS Benfold. Before he became captain, sailors couldn't get away from the ship fast enough. Today the vessel is the pride of the Pacific fleet, and sailors from other ships are clamoring to join its crew. In this firsthand account, Abrashoff explains how he got the ship and its crew back on course by breaking bad habits--personal and professional ones--and jettisoning old attitudes. During his 21 months aboard the Benfold, Abrashoff came to realize that in today's technology-intensive U.S. Navy, the traditional command-and control style wouldn't work. And it hadn't--the Benfold's 310 sailors had cheered derisively when Abrashoff's predecessor had left the ship. So he defied 225 years of navy tradition in his quest to engage the sailors in their work, increase their performance, and keep them around for their entire tours of duty. He retained his crew by redeeming them--showing them how to be not just better sailors but better people, too. That meant breaking them down when they were at their worst and then building them up to reach their best. It also meant personal redemption for Abrashoff; he resolved to really listen to what his sailors were saying. The result? Cost-saving ideas for the entire navy and surging confidence and commitment among crew members. PMID- 11213689 TI - Will disruptive innovations cure health care? PMID- 11213690 TI - Will disruptive innovations cure health care? PMID- 11213691 TI - Will disruptive innovations cure health care? PMID- 11213692 TI - Cheetah teams. AB - Your crucial new product is on the fast track, when suddenly a problem develops that threatens to derail it. Time to bring in the cheetah team. PMID- 11213693 TI - A better way to manage risk. AB - Through an innovative new policy forged with a single insurer, Honeywell is consolidating risks as diverse as fire protection and currency fluctuations--and saving a bundle. PMID- 11213694 TI - The law of the pack. AB - The value of the Internet lies in its connections, but some connections are more valuable than others. Which matter most? Reed's Law can tell you. PMID- 11213695 TI - Competing for supply. AB - The Internet was supposed to make it possible for anybody anywhere to get anything anytime. Instead, it's magnified suppliers' miscalculations into global shortages. But if the Net caused these supply chain woes, it's also the solution, says the CEO of a supply-chain software manufacturer. PMID- 11213696 TI - Marketing rules. AB - New research shows that the top-performing dot-coms aren't necessarily the ones with the best business models--they're the ones with the quickest, most responsive marketing. PMID- 11213697 TI - How we built a strong company in a weak industry. AB - When Roger Brown and Linda Mason decided to start a child care and early education company 15 years ago, they knew about the challenges inherent in the industry: no barriers to entry, low margins, few economies of scale, heavy regulatory oversight--to name just a few. But that didn't stop them. They eventually built Bright Horizons Family Solutions, a company that now has more than 340 high-quality child care centers, serving 40,000 children and employing 12,000 people. How did they do it? Sheer determination helped. But even more important, they developed a business model that took advantage of industry weaknesses. When the couple sat down to hash out a plan for the company, they realized that the key to achieving profitability and creating barriers to entry was to partner with companies. They could achieve higher returns by having those companies build and outfit the centers and, at the same time, boost customer loyalty. Indeed, Bright Horizon's corporate clients came to see the state-of-the art centers as a way to distinguish themselves in the eyes of current and prospective employees. The high-quality child care attracted the best employees and raised retention rates. Brown's first-person account describes the difficulties the couple and their company faced along the way, including the struggle for funding and a board that questioned Bright Horizons' business model and basic philosophy of good child care. But, Brown says, the commitment to a singular business model and the determination to make strengths out of weaknesses made the impossible possible. PMID- 11213698 TI - When to trust your gut. AB - Many top executives say they routinely make big decisions without relying on any logical analysis. Instead, they call upon their "intuition," "gut instinct," "hunches," or "inner voice"--but they can't describe the process much more than that. What exactly is gut instinct? In this article, author Alden Hayashi interviews top executives from companies such as America Online and Johnson and Johnson to find out how they make decisions. Hayashi also presents the research of leading scientists who suggest that our emotions and feelings might not only be important in our intuitive ability to make good decisions but may actually be essential. Specifically, one theory contends that our emotions help us filter various options quickly, even if we're not consciously aware of the screening. Other research suggests that professional judgment can often be reduced to patterns and rules; indeed, truly inspired decisions seem to require an ability to see similar patterns across disparate fields. A CEO who possesses that ability can craft a perfect strategy by detecting patterns that others either overlook or mistake for random noise. But various traits of human nature can easily cloud our intuitive decision making. One potential pitfall is our tendency to see patterns where none exist. Thus, continual self-checking and feedback are crucial, and some organizations have made these processes part of their corporate culture. PMID- 11213699 TI - Enlightened experimentation. The new imperative for innovation. AB - The high cost of experimentation has long put a damper on companies' attempts to create great new products. But new technologies are making it easier than ever to conduct complex experiments quickly and cheaply. Companies now have an opportunity to take innovation to a whole new level--if they're willing to rethink their R&D from the ground up. PMID- 11213700 TI - Finally, a way to put your Internet portfolio in order. AB - Eager to capitalize on the Internet's potential, many companies have allowed scores of on-line projects to bubble up throughout their organizations. The result? More harm than good, as companies find themselves confusing customers, aggravating employees, and wasting bushels of money. In this article, consultant Anthony Tjan explains how companies can do better. By adapting classical portfolio strategy to the digital age, executives can coordinate their Internet initiatives to avoid the needless headaches and spending, he says. Much of the market and industry data that underpin traditional portfolio analysis is unavailable for the Internet space, so Tjan replaces the two criteria used in traditional portfolio analysis--market position and industry attractiveness--with business viability and business fit. Viability captures the available quantitative data about an investment's likely payoff. Fit is qualitative; it measures the degree to which an investment dovetails with a company's existing processes, capabilities, and culture. Using viability and fit to assess their online initiatives, companies can then plot these efforts onto a simple matrix, called an Internet portfolio map. Their location on the matrix will suggest whether each initiative should be invested in, redesigned, sold or spun out, or killed. As Tjan notes, the process of organizing and evaluating new investment options against coherent, meaningful criteria isn't new. In the digital era, what is new are the tools you use. Internet portfolio planning is one such tool. PMID- 11213701 TI - Breakthrough bargaining. AB - Unspoken, subtle parts of a bargaining process--also known as the shadow negotiation--can set the tone for a successful negotiation. Deborah Kolb and Judith Williams, whose book The Shadow Negotiation was the starting point for this article, say there are three strategies businesspeople can use to guide these hidden interactions. Power moves are used when two negotiating parties hold unequal power--for instance, subordinates and bosses; new and existing employees; and people of different races, ages, or genders. These strategies, such as casting the status quo in an unfavorable light, can help parties realize that they must negotiate: they will be better off if they do and worse off if they don't. Process moves affect how negotiation issues are received by both sides in the process, even though they do not address substantive issues. Working outside of the actual bargaining process, one party can suggest ideas or marshal support that can shape the agenda and influence how others view the negotiation. Appreciative moves alter the tone or atmosphere so that a more collaborative exchange is possible. They shift the dynamics of the shadow negotiation away from the adversarial--helping parties to save face--and thus build trust and encourage dialogue. These strategic moves don't guarantee that all bargainers will walk away winners, but they help to get stalled negotiations moving--out of the dark of unspoken power plays and into the light of true dialogue. PMID- 11213702 TI - [Honestly--did you read the Helsinki declaration? A new version of the fundamental basis of medical research ethics]. PMID- 11213703 TI - [Routine use of placebos is questioned. Clear standpoint in the Helsinki declaration]. PMID- 11213704 TI - [Still a small problem with the mad cow disease? Creutzfeldt-Jakob disease and other prion diseases: current status]. AB - This review is based on recent published research on the BSE/CJD/vCJD problem mainly from UK, Germany and France. The situation in Sweden seems to be fortunate for several reasons. The use of meat and bonemeal as animal fodder was forbidden in this country 13 years ago. Sweden has not had any sheep with scrapie for many years. No animals with BSE have so far been found in our country. The incidence of sporadic CJD in this country followed retrospectively from 1985 to 1996 and prospectively from 1997 to 1999 has been around 1.2 per million per year with no significant increase. Only few cases of familial CJD are known. No patient with iatrogenic CJD has ever been found. The use of growth hormone derived from human pituitary glands was abandoned in 1985 when recombinant human growth hormone became available. So far there is no indication that any of the CJD cases diagnosed in Sweden has been of the vCJD type, the one linked to BSE. However, as the incubation period for prion diseases is very long and the Swedes are frequent travellers there is a risk that people from our country could have contracted vCJD through consuming meat products in countries with BSE. As a precaution the consumption of brain, spinal cord, lymphatic tissue, lungs, and gastrointestinal tract should be avoided. Human pituitary derived growth hormone is still available in some countries and might be illegally imported into Sweden. PMID- 11213705 TI - [Patient based care registries as a tool to follow up services]. AB - The Federation of Swedish County Councils and six medical specialties are working together in a project aiming to support and stimulate the development of patient based case registers as a tool to follow up, evaluate, develop and manage medical units. The project is based on participation on the part of the medical professions in a process-oriented way. Each case register shall be based on the individual patient, and will integrate inpatient and outpatient care, all medical professions and important procedures. In hematology the project also seeks to merge case costing data with the patient based case registers in order to facilitate more comprehensive cost analysis and comparison. This episodic perspective is useful for providers per se as well as in discussions between purchasers and providers as a method for understanding and analyzing medical services. The six specialties are hematology, obstetrics and gynecology, ophthalmology, otorhinolaryngology, dermatology and sexually transmitted diseases, and lastly psychiatry. PMID- 11213706 TI - [Family therapy appropriate even in somatic care. Study review of medically oriented family therapy]. AB - By observing and analyzing the influence of the therapist on the family as well as interactions between family members, the encounter with a family in a medical setting can serve to improve the health of its members, by improving their ability to use their own resources. This method of focusing on the interaction between individuals in a family or other systems has been a valuable addition to medical treatment of chronic disease. Family therapy has been shown to effectively improve treatment of diabetes, asthma and obesity. A review of the literature is presented. PMID- 11213707 TI - [How Hippocrates became the father of medicine]. PMID- 11213708 TI - [Meniere and lemology--comments and a reply]. PMID- 11213709 TI - [Difficult heart-questions: pacemaker, prolapse and downgrade]. PMID- 11213710 TI - [Craig Venter: higher intelligence is not always related to bigger genome]. PMID- 11213711 TI - [Role of the genetic code for public disease and behavior]. PMID- 11213712 TI - [Laughter is nothing to joke about. A quality of value for survival]. PMID- 11213713 TI - [Comment to the opinion-based campaign against neuropsychiatry]. PMID- 11213714 TI - [Urgent with an interdisciplinary conference on DAMP/ADHD]. PMID- 11213715 TI - [Scrutinize and diagnose the public environment of children, also]. PMID- 11213716 TI - [Seven criteria for clinical research ethics. Useful when used with love for medicine and patients]. PMID- 11213717 TI - [An appeal to support Christopher Gillberg's research and fight for children with neuropsychiatric disabilities]. PMID- 11213718 TI - [Physicians and psychiatrists in school health services in Stockholm: we know how important a correct diagnosis is for children with neuropsychiatric problems ]. PMID- 11213719 TI - [Shortage of psychotherapeutic methods in neuropsychiatric functional disorder]. PMID- 11213721 TI - [The myth about water]. PMID- 11213720 TI - [The National Board of Health and Welfare: 25 percent of general practitioners in other specialties]. PMID- 11213722 TI - Delaware's medicolegal investigation of death. Part 1. AB - In 1194, the coroner system was formally established in England with the original interest in death to protect the financial interest of the crown. This coroner system was brought to the United States during the early 1600s where the first recorded autopsy was performed in Massachusetts in 1647. Significant changes were made to improve upon the coroner system. In 1877, the first medical examiner system was established in the state of Massachusetts requiring that the coroner be supplanted by a physician known as a medical examiner. Using the system established in Massachusetts as a model, New York City developed an improved medical examiner system in 1915. The improvements made by New York City, under the leadership of men such as Drs. Charles Norris and Alex Gettler, essentially laid down the foundation for medical examiner systems and forensic toxicology throughout the country. Part II of this series will begin in Maryland. Maryland soon followed in New York City's footsteps and in 1939 developed the first statewide medical examiner system in the U.S. Influenced by systems such as Maryland's and New York City's, Delaware established a medical examiner system in 1955 to work alongside of the pre-existing coroner system. It was not until about a decade later in 1964 that the system became successful under the leadership of Dr. All Z. Hamell. In 1970, after 15 years of uphill battles with supporters of the antiquated coroner system, it was abolished, resulting in a statewide medical examiner system. Today, Delaware's medical examiner system has one of the best medicolegal investigative facilities in the country, complete with its own forensic sciences laboratory under the jurisdiction of a Chief Medical Examiner. Delaware's Office of Chief Medical Examiner will try to continue its tradition to serve as a model for other states and possibly other countries to follow. PMID- 11213723 TI - Litigation run amuck. PMID- 11213724 TI - Voluntary Initiative Program II. PMID- 11213725 TI - [Ultrastructure and elemental composition of frog bladder granular epithelial cells in normal state and upon stimulation of water transport]. AB - Changes in the frog urinary bladder granular cell ultrastructure were analysed in parallel with those in element composition of these cells after induction of water transport across the urinary bladder wall. Two ultrastructural (ultrathin section and freeze-fracture) methods were used in addition to two methods of object preparation for electron microprobe analysis--freeze-drying and freeze substitution. It has been shown that arginin-vasotocin stimulation of osmotic water flow across the urinary bladder wall causes certain morphological changes in the granular cells: decrease in electron density of the cytoplasm, depolymerization of the apical submembrane layer of actin microfilaments, increase in the number of sites of specific granules and apical membrane fusion, emergency of intramembrane particle aggregates in the apical membrane P-face. The quantitative electron microprobe analysis made it possible to reveal a statistically significant increase in sodium and calcium concentration and fall in that of potassium and chlorine in granular cells after water transport stimulation. A concentration gradient of sodium and potassium ions was seen to appear along the apical-basal axis in the cytoplasm of granular cells. Possible association between the obvious morphological transformations in granular cells and changes in their elemental composition has been discussed, in addition to some regulatory significance of calcium concentration increase in granular cells after arginin-vasotocin-induced osmotic water transport. PMID- 11213726 TI - [Stereologic analysis of vacuolization of the T-system of frog muscle fibers, detected using confocal fluorescence microscopy]. AB - The confocal fluorescence microscopy has been used for quantitative evaluation of the T-system reversible vacuoles produced by efflux of 80-120 mM glycerol from frog skeletal muscle fibers. The fibers were stained by membrane probe RH414 and by water-soluble dye fluorescein dextran that marks the vacuolar lumen. Using morphometrical and stereological methods the volume and surface densities of vacuoles were measured on single optical sections and Z-series during a 30 min glycerol efflux. Various methods of measurements (three-dimensional reconstruction of vacuoles, computer morphometry, point counting method) applied to the same Z-series provide similar results. The vacuolar membranes stained by RH414 look like bright rings 0.3-0.4 micron in width. It is concluded that the real position of vacuolar membrane corresponds to the middle of the vacuolar envelope. The measurements of the external dimensions of the envelope overestimate the stereological parameters up to 50%. The volume density of vacuoles reaches 10% within 20-30 min of glycerol efflux. It means that the volume of the T-system may increase by 25-30 times compared to the control value (0.3-0.4%). The surface density of vacuoles during reversible vacuolation is equal to 0.20-0.35 micron-1 and does not exceed the surface density of normal T system. The sufficiency of membrane material for the T-system reversible vacuolation is discussed in addition to the role of geometrical factor in this phenomenon. PMID- 11213727 TI - [Electrophoretic forms of glucose-6-phosphate dehydrogenase, acid phosphatase and esterase in Amoeba species amoebas]. AB - Glucose-6-phosphate dehydrogenase (G6PD), acid phosphatase and esterases in free living amoebae of 7 Amoeba species were investigated with the use of disc electrophoresis in polyacrylamide gel. The evidence provided is suggestive that the electrophoretic isoenzyme patterns of acid phosphatase and esterases (and G6PD in some cases), in addition to a few morphological characters, can serve as a taxonomic criterion for species identification within this genus, as well as for revealing erroneously classified species and strains. It is suggested that A. indica is an independent species whose preliminary diagnosis has been given in this paper. It is concluded that A. discoides and A. lescherae are strains of A. proteus, rather than two independent species. A and As-102 amoebian strains, kept in the collection of protozoan strains and species of the Institute of Cytology RAS and referred to as strains of A. proteus, belong in reality to another Amoeba species and even to another genus within the family Amoebidae. This conclusion has been documented by results of our analysis of electrophoretic patterns of acid phosphatase and esterases in these strains. PMID- 11213728 TI - [Effect of cytomedins on development of organotypic culture of various tissues from the internal organs of rats]. AB - Some natural peptides, referred to as cytomedines, were isolated from different organs: cortexin and epithalamin (both from the brain), cordialin (heart), hepalin (liver) and thymalin (thymus),--to test their stimulating effects on the growth in organotypic culture of different tissue explants taken from 3 day old rats. It has been found that these peptides exerted their obvious stimulating effects on the growth of the cultured explants, compared to the control, if taken in the respective concentrations: 100, 50, 50, 100 and 5 ng/ml. Thus, these cytomedins can be used in the clinical practice for stimulating reparative processes in the appropriate tissues. PMID- 11213729 TI - [Function of an inhibitor of cyclin-dependent kinase p27/Kip in cells transformed by E1A + E1B19 kDa + E1A + cHa-Ras, differing in their ability to realize a G1 block during serum starvation]. AB - We studied the capability of E1A + cHa-ras and E1A + E1B19kDa transformants to undergo the G1/S arrest of the cell cycle following depletion of serum growth factors. It has been shown that serum starvation induced the G1/S arrest both in normal rat embryo fibroblasts (REF) and in E1A + E1B19kDa transformants, whereas E1A + cHa-ras transformed cells lost this feature. To analyse the mechanisms underlying these differences, we studied the expression of p27/KIP, its intracellular distribution and association with E1A oncoproducts. The content of the p27/KIP inhibitor of cyclin-dependent kinases was found to change a little upon transformation by two complementary oncogene pairs. However, serum starvation for 24 h led to a significant increase in the content of p27/KIP in E1A + E1B19kDa transformants, while E1A + cHa-ras cells accumulated p27/KIP less markedly. According to the immunofluorescence study, the p27/KIP inhibitor is located in the nucleus of both normal and transformed cells. Moreover, serum starvation did not lead to its inhibition due to redistribution to the cytoplasm in both cell lines. Also, we were unable to detect association of p27/KIP with E1A oncoproducts in immunoprecipitated complexes. The obtained data indicate that, in contrast to E1A + cHa-ras transformants, in E1A + E1B19kDa cells the p27/KIP inhibitor is functional and it is capable of inducing the G1/S block after serum starvation. PMID- 11213731 TI - [Disruption of male meiosis in transgenic line tobacco res91]. AB - The course of meiosis in male-sterile trasgenic tobacco line res91 has been analysed. Cytological analysis included visualization of the spindle and phragmoplast. Abnormal meiosis was characterized with 1) cytomixis; 2) deformation of nuclei at prophase 2 in part of the cells, and lack of spindle formation in such cells at M2; 3) desorientation of spindles in meiosis 2. This set of abnormalities allows to suppose certain disturbancies of cytoskeleton during male meiosis in res91. PMID- 11213730 TI - [Both alpha1- and beta-adrenergic receptors participate in generation of a Ca2+ response to noradrenaline in murine brown preadipocytes]. AB - It has been shown that in Ca(2+)-signal generation, at the addition of norepinephrine (NE) to a suspension of freshly isolated brown preadipocytes, beta receptors participate alongside with alpha 1-adrenoreceptors. The amplitude of cell response to 10(-5)-10(-8) M NE is approximately equal to the sum of effects of alpha 1-specific agonists (oxymetazoline or cirazoline) and beta-selective agonist isoproterenol. beta-Selective antagonist nadolol practically completely prevented the effect of NE on the intracellular Ca2+ level, while phentolamine, an antagonist of alpha-receptors, caused only a approximately 25% inhibition of the cellular response. PMID- 11213732 TI - [Effect of age on frequency of heteroploidy in human oocytes]. AB - Human oocytes that failed to be fertilized in vitro were fixed for cytogenetic analysis. Successful karyotyping was achieved in 157 oocytes. Among women aged 23 35 years, 34% of oocytes were aneuploid and 8.6% diploid, while for women aged 36 39 years, these values exceeded 41 and 11.8%, respectively. The proportion of aneuploid and diploid oocytes increased significantly as the maternal age advanced. The rate of chromosomal abnormalities with age was analysed using methods of mathematical modelling. PMID- 11213733 TI - Vascular hamartoma of the orbit. AB - The aim of this presentation is to report a combined form of vascular malformation of the orbit. A 2-year-old girl had a four-month history of severe proptosis in the right eye. The patient had intermittent proptosis in association with a common cold. The globe was displaced downward and extraocular motility was markedly limited. Multiple intraconal and some extraconal cysts were removed with transcutaneous transseptal anterior orbitotomy. Histological examination showed several characteristics of vascular anomaly. There were malformatively dilated veins intermingled with dilated lymphatic channels, focal cavernous and capillary hemangiomatous features. This combined form of vascular anomaly can be presented as a venous lymphatic malformation associated with hemangiomatous features. PMID- 11213734 TI - Two cases of orbital infarction syndrome. AB - Orbital infarction syndrome is defined as ischemia of all intraorbital and intraocular structures. It is a rare disease caused by rich anastomotic vascularization of the orbit. It can occur secondary to different conditions, such as, acute perfusion failure, systemic vasculitis, orbital cellulitis and vasculitis. It results in orbital and ocular pain, total ophthalmoplegia, anterior and posterior segment ischemia, and acute blindness. We report here upon two cases of orbital infarction with similar presentations but with different causes, namely, mucormycosis and as a postoperative complication of intracranial aneurysm, discuss the possible mechanisms of orbital infarction, and present a review of the literature on the topic. The prompt recognition of clinical pictures and rapid diagnosis is essential for the early treatment of orbital infarction, since its progression is very rapid and it can be even fatal. PMID- 11213735 TI - Effect of zinc on the visual sensitivity of the bullfrog's eye. AB - There is a high concentration of zinc in ocular tissue, especially the retinachoroids, and the presence of physiological levels of zinc in these tissues seems essential for their normal function. The purpose of our study was to clarify this point using electroretinogram (ERG) recordings and spectrophotometer measurements before and after zinc treatment in a bullfrog's eye. The optimal zinc concentration used in this experiment was 1 microM ZnCl2, 100 microliters/6 ml ringer solution, with the result that the total zinc concentration in the ringer solution was 16.4 nM. To determine the effects of zinc on the retinal function, the changes of ERG parameters, such as threshold, a-, b- and c-waves and absorption spectra were observed before and after zinc treatment. It is noteworthy that high concentrations of zinc are present in the retina and the retinal pigment epithelium. Our results indicate that zinc treatment elevated the dark-adapted ERG threshold, all of the peak amplitudes of ERG were increased and rhodopsin regeneration was accelerated during visual adaptation. In spectral scans, absorbance increment due to zinc treatment was shown over the whole range of spectral scanning (300 nm-750 nm). We believe that zinc, which is abundant in the retina and the retinal pigment epithelium particularly, is an essential factor for the visual process and may be required to improve visual sensitivity during visual adaptation. PMID- 11213736 TI - Feeder vessel laser photocoagulation of subfoveal choroidal neovascularization. AB - We performed laser photocoagulation for extrafoveal feeder vessels in a series of 10 eyes with subfoveal choroidal neovascular membranes (CNVMs) in which feeder vessels could be detected by means of indocyanine green angiography using scanning laser ophthalmoscope. On the follow up indocyanine green angiograms performed within one week after treatment, successful occlusion of the feeder vessels with nonperfusion of the corresponding CNVMs was observed in 8 eyes (80%). Four eyes showed improved visual acuities with resolution of the exudative manifestation. But within 3 months, recanalization of the feeder vessels or further proliferation of the CNVMs developed in 7 eyes. We confirmed the possibility of infarction and regression of the CNVM by feeder vessel photocoagulation, which could improve the visual acuity. But it was rarely possible to maintain them. PMID- 11213737 TI - Axial length in branch retinal vein occlusion. AB - To determine the effects of axial length on the development of branch retinal vein occlusion (BRVO), determination of the affected eye, development of surgical complications, and visual prognosis, axial length was measured in 27 eyes each in surgical, non-surgical and control group and in 54 eyes each in occlusion (surgical + non-surgical group), non-affected eye (non-affected eyes of occlusion group), and non-occlusion group (both eyes of the control group). The average axial length was 22.61 mm in surgical, 22.48 mm in non-surgical, 23.09 mm in control, 22.55 mm in occlusion, 22.56 mm in non-affected eye, and 23.11 mm in non occlusion group. The axial length showed a statistically significant difference between surgical and control group (p = 0.018), between non-surgical and control group (p = 0.002), and between occlusion and non-occlusion group (p < 0.001); however, no statistically significant difference was seen between surgical and non-surgical group, between non-affected eyes of surgical and non-surgical group, and between occlusion and non-affected eye group. Also, in such as BRVO groups as surgical, non-surgical, and occlusion groups, no correlation was present between axial length and degree of visual acuity recovery and final visual acuity. Although the possibility of developing BRVO is higher in those with short axial length, the axial length may have no relationship with the determination of the affected eye, visual prognosis and development of surgical complications. PMID- 11213738 TI - Biomicroscopic vitreous observation using a 3 CCD video camera and a personal computer for image capture and archiving. AB - The purpose of this study is to evaluate the clinical usefulness of a newly developed biomicroscopic vitreous observation system. Vitreous observation was performed in 300 eyes with age- or disease-related vitreous changes using a 3 CCD video camera mounted on a slit-lamp biomicroscope and connected to a personal computer for real-time observation and especially for the capture and archiving of images. Various types of fundus lenses were used to scan the vitreous status systemically from the posterior pole to the vitreous base. This system allowed us to obtain and immediately review the images of the vitreoretinal relationship. The image quality was sufficient for clinical evaluation of the vitreous status. We were able to identify some variations of posterior vitreous detachments and clarify the changes of the vitreoretinal interface in the study eyes. This system is very useful for the dynamic observation and documentation of vitreous images in order to determine the role of vitreous in many vitreoretinal disorders. Furthermore it is more convenient and affordable than previous methods. PMID- 11213739 TI - Management of posteriorly dislocated intraocular lens using pars plana vitrectomy. AB - In order to evaluate the results of pars plana vitrectomy (PPV) for the treatment of posteriorly dislocated intraocular lens (PC-IOL), we retrospectively examined and analyzed the hospital records of patients who had undergone PPV to exchange or reposition a PC-IOL dislocated into the vitreous cavity. Of 20 eyes in 20 patients, IOL exchange was performed in 6 eyes, and IOL repositioning in 14 eyes. Posteriorly dislocated IOL occurred in 14 eyes during or within 2 days, and in 6 eyes 6 months after the IOL implantation. Thirteen eyes were surgically treated early after the occurrence, within 3 days, while 7 eyes were treated later, between 5 to 7 days. Compared with preoperative best-corrected visual acuity, the final visual acuity improved more than 2 lines in 12 eyes. With no significant difference on the statistics, earlier visual rehabilitation seemed to be shown in late-treated patients than in early-treated. Accordingly, a posterior dislocation of IOL can be successfully treated with PPV, and barring any serious complications such as retinal detachment, there is no need for surgery immediately following the occurrence. PMID- 11213740 TI - Telomerase activity in pterygeal and normal conjunctival epithelium. AB - All pterygia have similar histologic features of solar degeneration seen in the skin such as acanthosis, keratosis, or hyperkeratosis. Although the pathogenesis of pterygia is still unclear, an association with solar exposure, in particular with UV radiation, has been reported. Telomerase activity has been found to be higher in some degenerative, precancerous, and cancerous skin lesions. We investigated telomerase activity in the epithelium and the stromal tissues of the pterygium. Pterygeal tissues were obtained from 30 patients. Telomerase activity was measured with TRAPeze-ELISA kit. Three of the 28 (10.7%) pterygeal stromal tissues demonstrated positive telomerase activity. Fourteen of the 27 (51.9%) epithelial tissues were positive in telomerase activity, whereas telomerase activity was positive in only 3 of 9 normal epithelia (33.3%). Telomerase activity in the pterygium-covered epithelium was increased as compared with that seen in the normal epithelium, but the increase was not statistically significant. In conclusion, telomerase activity was somewhat increased in pterygeal tissues. Telomerase activity may be involved in the pathogenesis of pterygium. PMID- 11213741 TI - Congenital nasolacrimal duct obstruction: irrigation or probing? AB - The authors investigated the efficacy of antibiotic irrigation as the therapeutic option in congenital nasolacrimal duct obstruction. We retrospectively reviewed the medical record of 76 patients' eyes in whom congenital nasolacrimal duct obstruction had been diagnosed. In 50 of these patients, the colonizing microorganism was identified and, irrigation through canaliculi was performed using antibiotics of suitable sensitivity. Nasolacrimal system probing was performed on 26 patients as the control group. Treatment was regarded successful when over a 4 week period epiphora or mucous discharge disappeared and when saline passed without resistance on irrigation. 96.0% of patients in the irrigation group and 84.6% of patients in probing group were treated successfully. There was no statistical difference in the success rate between the two groups (P = 0.173). The recovery period based on culture results was 3.22 +/- 0.37 months in the group in which microorganisms were isolated and 2.39 +/- 0.35 months in the group in which no organisms were isolated. There were no statistically significant differences in the success rates between the group in which there was growth and the group in which there was no growth (P = 0.1308). Thus a similar result was obtained using nasolacrimal probing and canaliculus antibiotic irrigation in congenital nasolacrimal duct obstruction. Antibiotic irrigation is a safe and simple therapeutic option in congenital nasolacrimal duct obstruction. PMID- 11213742 TI - Hepatocellular carcinoma metastatic to the orbit. AB - Orbital metastases of hepatocellular carcinoma are rare. The authors report a case of hepatocellular carcinoma metastatic to the orbit. A 56-year-old woman with hepatitis B infection as confirmed serologic test for hepatitis B surface antigen (HBsAg) demonstrated superior displacement of the left eyeball. The clinical appearance of the patient demonstrated an inferior displacement of the right eye. MRI disclosed an orbital mass that extended toward the lower eyelid and into the temporal fossa with destruction of the lateral orbital wall. Upon subsequent abdominal computed tomographic scans, the primary tumor was found in the liver. A biopsy specimen of the orbit showed trabecular structures with eosinophilic cytoplasm. Bile canaliculi and sinusoids were also seen. The tumor cells showed vesicular nuclei with mitoses. Immunohistochemical markers such as high-molecular-weight keratin and alpha-fetoprotein showed a positive response. However, immunohistochemical markers such as low-molecular-weight keratin and polyclonal carcinoembryonic antigen showed as negative. We diagnosed the tumor as a hepatocellular carcinoma metastatic to the orbit. A review of the pertinent literature disclosed relatively few occurrences of hepatocellular carcinoma metastasizing to the orbit. PMID- 11213743 TI - Web sites, portals, and channels: e-strategies for consumer relationship management. PMID- 11213744 TI - A realistic outlook for Web strategy. PMID- 11213745 TI - Ten Internet strategies for connecting with health consumers. PMID- 11213746 TI - Retaining good employees in tough times. Part II: Six strategies for retention. PMID- 11213747 TI - Aggressive nutrition intervention. Staff training is key to ensuring positive outcomes. PMID- 11213748 TI - Assessment of patients (PE). PMID- 11213749 TI - Enhancing working conditions and patient safety. PMID- 11213750 TI - CDC looks to update HIV guidelines. PMID- 11213751 TI - Conflict to cooperation: integrating social work into your CM model. AB - Ann Marie Distasio, RN, BSN, MSA, became acutely aware of the turf battle between RN case managers and social workers when she began work as the director of case management at Memorial-Hermann Memorial City Hospital in Houston. She saw a real fear in her social workers that their importance to the department was compromised. But a common goal among hospitals is a revised approach to case management that negates the fear. It enforces a sharing philosophy, making sure that each discipline's expertise is used most appropriately to advance the best patient management. PMID- 11213752 TI - Reclaim your denials to help save bottom line. AB - Johns Hopkins Hospital in Baltimore provides an excellent real-life example of how to manage claims denials for increased reimbursement. Hopkins gained more than $2 million when it revised its policies and procedures regarding claims denials. Jon Mayer, RN, FNP, MBA, a management consultant with Chicago-based Milliman and Robertson Inc., suggests getting case management involved early, at the contract negotiation stage. PMID- 11213753 TI - Cultural competence is a must for all hospitals. AB - It makes sense to move your facility to an attitude of cultural competency, not only because there are certain minimum requirements from the Joint Commission on Accreditation of Healthcare Organizations in Oakbrook Terrace, IL, and other watchdogs, but also because it's the right thing to do, according to Beth Remus, an expert in the field of cultural awareness and competency in health care. PMID- 11213754 TI - Pathway achieves first steps toward improvement. AB - In 1999, Pomona Valley Hospital in Claremont, CA, saw a real need to revise its treatment of community-acquired pneumonia. After a thorough chart review and development of a new pathway, the case management team has taken an important step toward a standard of care. PMID- 11213755 TI - Higher risk of re-admits when patient can't read. PMID- 11213756 TI - Hiring how-to: use the Internet as supplement. AB - Although the Internet generally is the first place people look for job opportunities these days, Elaine Cohen, EdD, RN, director of case management at the University of Colorado Health Services Center in Denver, does not see a real need to go on-line for qualified case manager candidates. However, Cohen acknowledges that the Internet is a good tool to contact and interact with potential employees. PMID- 11213757 TI - Special report: building a successful CM career. Directory of the top 12 CM credentials. PMID- 11213758 TI - A preliminary functional brain study on amputees. AB - The purpose of this study was to verify whether brain activation could be used to modulate the movements of an artificial limb. This approach was begun 20 years ago with the fitting of prostheses immediately following lower-limb amputations. We studied 9 unilateral amputees and 9 control participants using functional MRI, electroneuromyography, gait laboratory, and neuropsychological assessments. The results demonstrated that brain activation is analogous when participants in the control group are asked to mentally move a foot, compared with amputees who are asked to move a nonexistent foot. The brain has not been damaged and maintains its areas of command. This can be applied in rehabilitation. PMID- 11213759 TI - Multiple imputation and posterior simulation for multivariate missing data in longitudinal studies. AB - This paper outlines a multiple imputation method for handling missing data in designed longitudinal studies. A random coefficients model is developed to accommodate incomplete multivariate continuous longitudinal data. Multivariate repeated measures are jointly modeled; specifically, an i.i.d. normal model is assumed for time-independent variables and a hierarchical random coefficients model is assumed for time-dependent variables in a regression model conditional on the time-independent variables and time, with heterogeneous error variances across variables and time points. Gibbs sampling is used to draw model parameters and for imputations of missing observations. An application to data from a study of startle reactions illustrates the model. A simulation study compares the multiple imputation procedure to the weighting approach of Robins, Rotnitzky, and Zhao (1995, Journal of the American Statistical Association 90, 106-121) that can be used to address similar data structures. PMID- 11213760 TI - Symmetrically dependent models arising in visual assessment data. AB - Given data from bilateral visual assessments on N subjects at k occasions, we consider inference for contralateral correlations (C) between fellow eyes and lateral correlations (L) among p different assessments of the same eye. Under permutation symmetric dependence structure between observations from fellow eyes and among observations from the same eye, we obtain maximum likelihood estimates of L, C, and L-C. Based on the large-sample estimates of the corresponding covariance structures, we test the hypothesis that the association between fellow eyes is constant across time and the hypothesis that lateral and contralateral associations between any two occasions are the same. PMID- 11213762 TI - OIG to target ineligible SNF stays, duplicative payments in fiscal 2001. PMID- 11213761 TI - A diagnostic for Cox regression with discrete failure-time models. AB - Changes in maximum likelihood parameter estimates due to deletion of individual observations are useful statistics, both for regression diagnostics and for computing robust estimates of covariance. For many likelihoods, including those in the exponential family, these delete-one statistics can be approximated analytically from a one-step Newton-Raphson iteration on the full maximum likelihood solution. But for general conditional likelihoods and the related Cox partial likelihood, the one-step method does not reduce to an analytic solution. For these likelihoods, an alternative analytic approximation that relies on an appropriately augmented design matrix has been proposed. In this paper, we extend the augmentation approach to explicitly deal with discrete failure-time models. In these models, an individual subject may contribute information at several time points, thereby appearing in multiple risk sets before eventually experiencing a failure or being censored. Our extension also allows the covariates to be time dependent. The new augmentation requires no additional computational resources while improving results. PMID- 11213763 TI - Paying the piper: HCFA guidance on survey revisits raises concerns about continuation of penalties. PMID- 11213764 TI - What to do when Medicare asks for its money back. Part I: The top reasons for post-payment denials. PMID- 11213765 TI - Small employers give coverage a big boost. PMID- 11213766 TI - Who'll get soaked if Medicare covers drugs? PMID- 11213767 TI - E-health, your workforce and you. PMID- 11213768 TI - Retiree benefits just fading away. PMID- 11213769 TI - Union Pacific ... on the right track. PMID- 11213771 TI - DataWatch. Premiums rise while employee share drops. PMID- 11213770 TI - Blocked laws and bad language. PMID- 11213772 TI - Words for the wise. To make your message heard, it's best to paint a verbal picture. PMID- 11213773 TI - The fear factor. PMID- 11213774 TI - Synthesis of new pyridoquinoxalines, thienopyridoquinoxalines and pyrimidothienopyridoquinoxalines. AB - Synthesis of 3-chloro-2-cyanoquinoxaline (1) and its reactions with sodium azide, guanidine hydrochloride, semicarbazide and thioheterocycles have been investigated (2-7). Also, the reaction of the chloro compound 1 with cyanoacetamide or cyanothioacetamide gave the pyrido[2,3-b]quinoxaline derivatives 8, 9. Compound 9 was used as a key intermediate to produce the more polyheterocyclic systems 10-18. PMID- 11213775 TI - Perceived need for and use of mental health services by women living with or at risk of human immunodeficiency virus infection. AB - OBJECTIVES: To determine prevalence of and factors associated with perceived need for and use of mental health services and use of psychotherapeutic medications among women in the Human Immunodeficiency Virus Epidemiology Research Study (HERS). METHODS: We interviewed 871 HIV-seropositive and 439 demographically and behaviorally similar seronegative women at baseline regarding demographics, psychosocial measures, substance use, medical history, and use of health care services and medications. RESULTS: Thirty-eight percent of HIV-seropositive women and 35% of seronegative women (p = 0.33) reported needing mental health services in the prior six months. Women who were older, were white or Latina (compared with African American), had some college education, had less social support, and reported recent negative life events or had CES-D scores higher than 15 (suggesting depression) were more likely to report needing mental health services. Sixty-seven percent of seropositive and 65% of seronegative women who reported needing services (p = 0.69) reported obtaining services. Women who were white (compared with Latina or African American) and had more education, more social support, and health insurance were more likely to obtain services. Eighteen percent of seropositive and 13% of seronegative women (p = 0.006) reported current use of psychotherapeutic medications, especially antidepressants and antianxiety medications. Women who reported use of medications were more likely to report recent negative life events; were older, white, or Latina; had more education, less social support, CES-D scores higher than 15, and health insurance. CONCLUSION: Women both living with or at risk of HIV perceived a need for and used mental health services in association with negative life events, social isolation, and depressive symptoms. Need for and use of services differed by race/ethnicity, education, and availability of social support. PMID- 11213776 TI - Use of cyclosporin A as a steroid sparing agent in cystic fibrosis. PMID- 11213777 TI - Survey of criteria used to diagnose allergic bronchopulmonary aspergillosis in cystic fibrosis. PMID- 11213778 TI - Subnormal growth in children with Helicobacter pylori infection. PMID- 11213779 TI - Growth monitoring. PMID- 11213780 TI - Detecting outbreaks of E coli O157 infection in nurseries. PMID- 11213781 TI - Meningococcal disease due to W135: fresh public health concerns. PMID- 11213782 TI - Prevention and treatment of cow's milk allergy. PMID- 11213783 TI - Pyridoxine dependent and pyridoxine responsive seizures. PMID- 11213784 TI - Are sleep studies worth doing? PMID- 11213785 TI - Data presented do not justify pessimistic conclusions. PMID- 11213786 TI - Spacers and holding chambers: not the last word, we hope. PMID- 11213787 TI - The Collaborative Longitudinal Personality Disorders Study: reliability of axis I and II diagnoses. AB - Both the interrater and test-retest-retest reliability of axis I and axis II disorders were assessed using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and the Diagnostic Interview for DSM-IV Personality Disorders (DIPD-IV). Fair-good median interrater kappa (.40-.75) were found for all axis II disorders diagnosed five times or more, except antisocial personality disorder (1.0). All of the test-retest kappa for axis II disorders, except for narcissistic personality disorder (1.0) and paranoid personality disorder (.39), were also found to be fair-good. Interrater and test-retest dimensional reliability figures for axis II were generally higher than those for their categorical counterparts; most were in the excellent range (> .75). In terms of axis I, excellent median interrater kappa were found for six of the 10 disorders diagnosed five times or more, whereas fair-good median interrater kappa were found for the other four axis I disorders. In general, test-retest reliability figures for axis I disorders were somewhat lower than the interrater reliability figures. Three test-retest kappa were in the excellent range, six were in the fair-good range, and one (for dysthymia) was in the poor range (.35). Taken together, the results of this study suggest that both axis I and axis II disorders can be diagnosed reliably when using appropriate semistructured interviews. They also suggest that the reliability of axis II disorders is roughly equivalent to that reliability found for most axis I disorders. PMID- 11213789 TI - [Secondary hyperparathyroidism]. PMID- 11213788 TI - The Collaborative Longitudinal Personality Disorders Study: development, aims, design, and sample characteristics. AB - This paper describes the aims, background, design, and methods used in a collaborative longitudinal study of Axis II personality disorders (PDs). This study examines the putative stability of selected PD diagnoses and criteria, what factors affect their course, and whether their stability and course distinguishes them from a representative Axis I disorder. This article also describes the acquisition and demographics of the sample on whom the study is being done. A prospective, repeated measures investigation of the stability of PDs is now underway at multiple clinical settings in four collaborating urban sites in Boston. New Haven, New York, and Providence. Diagnostic assignments are based on semistructured interview assessments (by clinically trained raters) and confirmed by at least one additional contrasting diagnostic method. The sample consists of 668 treatment seeking and reliably diagnosed adults recruited from a broad range of clinical sites. By design, patients in the sample met standards for one of five diagnostic subgroups: (a) schizotypal (N = 86); (b) borderline (N = 175); (c) avoidant (N = 157); (d) obsessive-compulsive (N = 153) personality disorders or a control group having (e) major depressive disorder without personality disorder (N = 97). PMID- 11213791 TI - Preformulation experiences and in vitro model studies with spironolactone containing suppositories. AB - The optimal suppository base for the formulation of rectal suppositories containing diuretic spironolactone was selected experimentally. Model studies were carried out about the effect of solubility-increasing additives on the release of the drug from the suppositories. During the in vitro examinations acceptor phases of different pH values were used, and both diffusion time and the number of samplings were changed. Among the lipophilic and hydrophilic suppository bases studied the hydrophilic Macrogolum 1540 was found to be optimal. The release and diffusion of spironolactone was the most favourable from these suppositories. During storage these suppositories remained stable and the values of release did not decrease significantly (p < 0.05). PMID- 11213790 TI - Tobacco use among high school students in Buenos Aires, Argentina. AB - OBJECTIVES: This study assessed the prevalence and correlates of tobacco use among high school students in Buenos Aires, Argentina. METHODS: Anonymous, self administered questionnaires were given to 3909 8th and 11th graders in a stratified random sample of 49 public and private schools. The instrument included items from American surveys, translated and validated among Argentinean teens. Multiple logistic regression analysis was used to estimate possible effects on smoking behavior of environment, students' personal characteristics, and their knowledge, beliefs, and attitudes regarding smoking. RESULTS: Of 8th and 11th graders, 20% and 43%, respectively, were classified as current smokers. Overall, 29% of males and 32% of females were current smokers. Students attending public schools were more likely to smoke than those in private schools (P < .05). Current smoking was associated with having a best friend who smokes, reporting that more than 50% of friends of the same sex smoke, having positive attitudes and beliefs toward smoking, and having a positive intention to smoke within the next year (all P < .001). CONCLUSIONS: Over 20% of the 8th graders in our sample were current smokers; prevention efforts must therefore start early. PMID- 11213792 TI - Influence of curing tip distance on composite Knoop hardness values. AB - The purpose of this paper was to study the influence of curing tip distance on Knoop hardness values, at different depths, of two composites, Z100 and Silux Plus. Specimens (5 mm in diameter and 2.5 mm in height) were prepared in a copper mold, covered with mylar strip and polymerized for 40 s, at 3 tip-to-composite surface distances: 0 mm (surface contact), 6 and 12 mm, utilizing an XL 3000 curing unit, with 750 mW/cm2 power. The specimens were then stored at 37 degrees C for 24 h. Knoop hardness values were measured using a microhardness tester, with a load of 50 g for 30 s for each indentation. Four specimens were made for each distance and composite and eighteen indentations were made of each specimen. The results were submitted to analysis of variance and Tukey test at 5% significance level. The results indicated that 1) composite Z100: the larger the curing tip distance in relation to the composite, the lower the Knoop hardness values; 2) Silux Plus: increasing the curing tip distance did not produce a statistically significant difference in the Knoop hardness values; however, at 6 and 12 mm, the deeper layers showed lower Knoop hardness values in relation to the surface; 3) Z100: statistically superior in relation to Silux Plus at all three curing tip distances and at all depths (P < 0.05). PMID- 11213793 TI - A clinical evaluation of materials for interocclusal registration in centric relation. AB - Four techniques for interocclusal registrations of centric relation based on materials or combinations of materials usually utilized were tested by means of mounting of casts for a patient with partial lower edentulousness, without a free end saddle. To ensure the correct position of centric relation a Lucia jig was utilized. The following conditions for the record of posterior section were tested: registrations with wax, wax plus zinc oxide-eugenol paste, wax plus Duralay acrylic resin, and condensation silicone (putty). The evaluation was made by the measure of vertical distance between reference points in the base of the casts and calculation of variations occurring with each material. The combinations of wax plus zinc oxide-eugenol paste and wax plus Duralay acrylic resin showed the smallest variations in centric relation position. PMID- 11213794 TI - Tooth wear and loss: symptomatological and rehabilitating treatments. AB - The authors report a clinical case that presented tooth wear and absence, with painful muscular and articular symptomatology, and also alteration in deglutition, mastication and speech. The clinical procedures used were re establishment of vertical dimension of occlusion, mandibular centric relations, and occlusal contacts through therapeutic removable partial dentures. The condyle position was analyzed in habitual occlusion and in occlusion with dentures, through transcranial radiographs of the temporomandibular joints. Oral rehabilitation was achieved with dental restoration and removable partial dentures. PMID- 11213795 TI - Wiskott-Aldrich syndrome protein and platelets. AB - Wiskott-Aldrich syndrome (WAS) and X-linked thrombocy topenia (XLT) are caused by mutations of the WAS protein (WASP) gene. The manifestations of the classic WAS phenotype consist of immunodeficiency, eczema and thrombocytopenia. However, thrombocytopenia and small platelets are the only consistent features of WAS and XLT. The exact mechanisms of the development of thrombocytopenia in patients with WAS or XLT are unknown. To date, platelets are the only primary cells in which inducible tyrosine phosphorylation of WASP has been consistently demonstrated. This review focuses on the recent progress in dissecting the causes of thrombocytopenia and the emerging understanding of WASP phosphorylation. PMID- 11213796 TI - The Wiskott-Aldrich syndrome: disordered actin dynamics in haematopoietic cells. AB - The Wiskott-Aldrich syndrome protein (WASp) is a member of a unique family whose members share similar domain structures and are responsible for the transduction of signals from the cell membrane to the actin cytoskeleton. For WASp, the interactions with Rho family GTPases and the cytoskeletal organising complex Arp2/3 are critical to these functions, which when disturbed translate into abnormalities of haematopoietic cell signaling, polarisation, migration and phagocytosis. This review discusses the evidence for regulation of highly dynamic cytoskeletal structures by WASp and the consequences of disturbed function on some of these processes. PMID- 11213797 TI - Human interferon-gamma-mediated immunity is a genetically controlled continuous trait that determines the outcome of mycobacterial invasion. AB - Individuals with inherited disorders of interferon gamma (IFN-gamma)-mediated immunity appear to be specifically vulnerable to mycobacterial infections. The severity of clinical features of affected individuals differs between cases. Some patients die of mycobacterial infection in early childhood, whereas others have long asymptomatic periods in childhood and as adults. This rare syndrome also shows high allelic and non-allelic genetic heterogeneity. Mutations in IL12B, encoding the interleukin (IL)-12 p40 subunit, and in IL12RB1, encoding the beta1 chain of the IL-12 receptor, result in impaired IFN-gamma production. Mutations in IFNGR1 and IFNGR2, encoding the two IFN-gamma receptor chains, and mutations in STAT1, encoding an essential signaling component, result in impaired cellular responses to IFN gamma. Different types of mutation define two types of complete and two types of partial IFNgammaR1 deficiency. Complete and partial IFNgammaR2 deficiency have also been described. We herein compare the genotypes, cellular phenotypes, and clinical phenotypes of healthy individuals and patients with the seven known genetic disorders impairing cellular responses to IFN-gamma. Patients with defective IFN-gamma production were not considered in this study. The mutations and clinical features of patients with IFNgammaR1, IFNgammaR2, and STAT 1 deficiency are reviewed. Selected cell lines from each of the eight groups were tested for their response to IFN-gamma. We find that individuals may be classified into four broad groups based on genotype, cellular phenotype, and clinical phenotype (normal individuals and patients with mild, intermediate, or severe disease). This correlation suggests that IFN-gamma-mediated cell activation is a genetically controlled quantitative trait and that it determines the outcome of mycobacterial invasion in man. PMID- 11213798 TI - Gene therapy of severe combined immunodeficiencies. AB - Primary immunodeficiency diseases (PID) are attractive candi dates for a gene therapy approach because many of these disorders convey a poor prognosis while a number of the genes mutated in these conditions have been identified. Gene transfer into hematopoietic stem cells (HSC) should, in theory, lead to a cure of the disease. There are, however, a number of limitations mostly related to the failure of clinically available vectors to enable transgene integration into HSC. Nevertheless PID due to a gene defect leading to failure of cell development could be amenable to gene therapy given the selective advantage conferred to transgene expression in progenitor cells. Terminally differentiated cells are, however, long lived, as is the case for T lymphocytes. This concept led to the first gene therapy trials for adenosine deaminase (ADA) deficiency several years ago. Results were in part disappointing mostly because of the concomitant substitutive treatment by polyethylene glycol-ADA. However, recent application to X-linked severe combined immunodeficiency (gamma(c) deficiency) turned out to be efficient at least on a relatively short term basis (i.e. one year so far). These results demonstrate that this concept is valid and can be the basis for the treatment of other forms of severe T-cell immunodeficiencies. Obviously, development of vectors (lentiviruses) able to efficiently target HSC could in the future considerably enlarge the field of PID treatable by gene transfer. PMID- 11213799 TI - Leukocyte adhesion deficiency II-from A to almost Z. AB - Leukocyte adhesion deficiency (LAD) type II is the second human disorder identified which involves the adhesion cascade. While in LAD I the integrin family is defective, in LAD II the selectin system is involved. The syndrome has been described in only five patients and is transmitted as an autosomal recessive trait. The infectious episodes and the severity are much milder than those observed in LAD I, and the only persistent clinical symptom is chronic severe periodontitis. Delay separation of the umbilical cord, which is a hallmark for LAD I, was not observed in any of the LAD II patients. The exact defect in the system is absence of the SLeX, which is an important ligand for the selectin on the leukocyte lead ing to a profound defect in leukocyte rolling, the first step in the adhesion cascade. This causes a marked decrease in chemotaxis accompanied by pronounced neutrophilia. Apart from the leukocyte defect, these patients suffer from severe growth and mental retardation and exhibit the rare Bombay blood group type. The primary defect in the syndrome is in fucose metabolism, with the absence of all fucosylated glycans on cell surface membranes. Recently, it is was found that the defect is in a specific transporter of GDP fucose into the Golgi apparatus, and thus no fucosylation process takes place, and no surface expression can be detected. The exact genetic defect in the transporter is still unknown. Four of the patients were of Arabic origin while the fifth was of Turkish origin. It seems that the primary defect is somewhat different and, therefore, fucose administration was effective in the Turkish child, but did not show any beneficial results in the patients of Arabic origin. PMID- 11213800 TI - Lessons from the bare lymphocyte syndrome: molecular mechanisms regulating MHC class II expression. AB - Major histocompatibility complex class II (MHCII) molecules drive the development, activation and homeostasis of CD4* T-helper cells. They play a central role in key processes of the adaptive immune system, such as the generation of T-cell-mediated immune responses, the regulation of antibody production and the development and maintenance of tol erance. It is thus not surprising that the absence of MHCII expression results in a severe primary immunodeficiency disease (the bare lymphocyte syndrome (BLS)). The genetic defects responsible for BLS do not lie within the MHCII locus, but in genes encoding transcription factors required for MHCII expression. A great deal of our current knowledge about the mechanisms regulating expression of MHCII genes has been derived from the study of BLS. Four different MHCII regulatory genes have been identified. These genes encode RFXANK, RFXS, RFXAP and CIITA. The first three are subunits of RFX, a ubiquitously expressed factor that binds to the promoters of all MHCII genes. RFX binds co-operatively with other factors to form a highly stable multiprotein complex referred to as the MHCII enhanceosome. This enhanceosome serves as a landing pad for the co-activator CIITA, which is recruited via protein-protein interactions CIITA is the master control factor for MHCII expression. The highly regulated expression pattern of CIITA ultimately dictates the cell type specificity, induction and level of MHCII expression. PMID- 11213801 TI - Complement: a critical test of its biological importance. AB - The biological activities of the more than 30 proteins that comprise the complement system have been elucidated in parallel lines of investigation that resulted in the purification of the proteins and studies of their function in vitro. Twenty years ago, the first complement cDNA clones were generated. Subsequently the structure and chromosomal localization of the complement genes and the primary sequences of their gene products were revealed. For some, even their higher order structure was solved. This work, coupled with studies of complement gene expression, biosynthesis, post-synthetic processing and secretion, contributed to an analysis of the relatively rare naturally occurring genetic deficiencies of complement proteins discovered fortuitously in humans sand experimental animals. Not until the past 5 years, with the application of methods for manipulating genes in vivo (targeted deletion and overexpression), has it been possible to definitively assign specific functions to complement proteins and to assess their importance in the intact organism. These relatively recent studies have confirmed the in vitro work or revealed unexpected roles for complement effector and regulatory proteins in host defenses, specific immunity, immunopathology, metabolism and reproductive biology This work is reviewed and the implications for understanding human diseases and the design of novel pharmaceutical agents are discussed. The promise of this line of investigation is certain but the context imposed by gender, developmental stage, other genes and environment must be taken into account before the practical implications of this deeper understanding of complement biology are fully realized. PMID- 11213802 TI - Novel immunodeficiency data servers. AB - The Internet contains scientific information in increasing amounts. It is possible to obtain the latest information, and Web services can easily be maintained and updated. We have set up three Internet services on immunodeficiencies. Immunodeficiency-related mutation infor mation is available in immunodeficiency mutation databases (IDbases). Currently 14 registries are distributed, including information about Bloom syndrome (BLMbase), X-linked agammaglobulinemia (BTKbase), X-linked and autosomal recessive chronic granulomatous diseases (CYBBbase for X-linked CGD, CYBAbase for p22(phox) deficiency, NCF1base for p47(phox) deficiency, NCF2base for p67(phox) deficiency), CD3gamma and CD3epsilon deficiencies (CD3Gbase, CD3Ebase), X-linked hyper-IgM syndrome (CD40Lbase), T-B+ severe combined immunodeficiency (JAK3base), V(D)J recombination defects (RAG1base, RAG2base), X-linked lymphoproliferative syndrome (SH2D1Abase), and ZAP-70 deficiency (ZAP70base). Information on laboratories analysing the genetic defects is collected to IDdiagnostics registry. Due to the rareness of immunodeficiencies there are very few laboratories performing genetic diagnostics. Such laboratories are listed in IDdiagnostics and physicians can use the registry to find a suitable laboratory for their diagnostic needs. Immunodeficiency Resource (IDR) is a comprehensive integrated knowledge base for all the information on immunode ficiencies, including clinical, biochemical, genetic, structural and computational data and analyses. All three services are available at http: //www.uta.fi/imt/bioinfo/. PMID- 11213803 TI - X-linked lymphoproliferative disease is caused by deficiency of a novel SH2 domain-containing signal transduction adaptor protein. AB - X-linked lymphoproliferative disease (XLP) is an inherited immunodeficiency, involving primarily T and natural killer (NK) cells, which in the majority of cases exacerbates following exposure to Epstein-Barr virus (EBV). Prior to EBV infection, most boys with the defective XLP gene appear to be clinically healthy EBV infection in males with the defective XLP gene leads to three main phenotypes: severe and mostly fatal infectious mononucleosis (58%), lymphoproliferative disorders mostly of B-cell origin (30%) and/or dysgammaglobulinemia (31%). Later in life, dysgammaglobulinemia and malignant lymphoma may also develop in about 53% and 56% of EBV-negative XLP males, respectively This fact suggests that EBV may only act as a potent trigger of the earliest and most serious clinical phenotype of XLP, i.e. fatal infectious mononucleosis. XLP has an unfavorable prognosis. Successful transplanta tion of hematopoietic stem cells can cure this immunodeficiency In the future, gene therapy may eventually become an additional option to prevent XLP. The gene responsible for XLP, SH2-domain containing gene 1A (SH2D1A) has recently been identified and sequenced. SH2D1A encodes a polypeptide of 128 amino acids containing a single SH2 domain. Until now, 45 different SH2D1A gene mutations have been identified in patients with XLP SH2D1A is thought to play an important role in signal transduction in T and NK cells. In vitro, SH2D1A has been shown to interact as an adaptor protein with the signaling pathways through SLAM, a T-cell co-stimulatory molecule, and 2B4, an NK-cell-activating receptor. Further functional studies of the SH2D1A protein will probably provide new insights into the pathogenesis of severe infectious mononucleosis, malignant lymphomas and immunodeficiency in patients with XLP. PMID- 11213804 TI - Hematopoietic stem cell gene therapy: towards clinically significant gene transfer efficiency. AB - Early clinical gene therapy and gene marking trials using retroviral vectors to transduce hematopoietic stem cells (HSC) revealed two major shortcomings of this new treatment modality. One was insufficient expression or even silencing of the integrated vector sequences, and the second was the low gene transfer efficiency achieved to in vivo repopulating cells. It became clear that neither rodent models nor human in vitro surrogate assays for stem cells were predictive of in vivo transgene levels in human target cells. Using the rhesus monkey model we have focused on improving gene transfer efficiency into HSC. Immune rejection of trans duced cells has been shown to occur in mature peripheral target cells such as lymphocytes or myocytes. Our studies and those from other investiga tors suggest that transgenes introduced via HSC induces immunologic tolerance towards the foreign product. In vivo priming of target cells, i.e. mobilization of HSC into the circulation with granulocyte colony stimulating factor and stem cell factor, as well as optimization of the in vitro transduction conditions, now allow a stable in vivo gene transfer efficiency of up to 10-15% in both lymphoid and myeloid circulating cells in non-human primates, levels that would be adequate for many clinical applications. PMID- 11213805 TI - Of genes and phenotypes: the immunological and molecular spectrum of combined immune deficiency. Defects of the gamma(c)-JAK3 signaling pathway as a model. AB - Cytokines play a major role in lymphoid development. Defects of the common gamma chain (gamma(c)) or of the JAK3 protein in humans have been shown to result in a severe combined immune deficiency (SCID), with a profound defect in T and natural killer (NK)-cell development, whereas B-cell generation is apparently unaffected (T-B+NK-SCID). While extensive molecular and biochemical analysis of these patients has been instrumental in understanding better the biological properties of the gamma(c) and JAK3 protein, an unexpected phenotypic heterogeneity of gamma(c) and JAK3 deficiency has emerged, indicating the need for appropriate and extensive investigations even in patients with atypical presentations. At the same time, characterization of the defects has been instrumental in the development of novel therapeutic approaches, from in utero hematopoietic stem cell transplantation to gene therapy. PMID- 11213806 TI - The cellular phenotype conditions Btk for cell survival or apoptosis signaling. AB - Bruton's agammaglobulinemia tyrosine kinase (Btk) was identified as the gene mutated in X-linked agammaglobulinemia. Btk is involved in B-cell receptor signaling and B cell ontogeny as the disease is characterized by a block in B cell development. Cell proliferation and apoptosis are integral parts of B-cell development. We have demonstrated that overexpression of Btk in HeLa cells led to apoptosis, whereas in B cells, en dogenous levels of Btk protected the cells from apoptosis. We suggest a dual role for Btk in apoptosis and cell survival. We further propose that the phenotype of the cell may direct Btk for either cell survival or apoptosis. Our model is in line with the general feature of mammalian cells that have the inherent property to die unless the survival signals are triggered. The interplay between survival and apoptotic signaling is regulated by cell sur face receptors, cytoplasmic and nuclear regulatory molecules. These regu latory molecules may be simple unidirectional regulators or bidirectional regulators such as Btk. The different molecules involved in these pathways bring about an orchestrated signal depending on the phenotype of the cell, and a cell type-specific biological response is achieved that decides the fate of the cell. PMID- 11213807 TI - Experiments of nature: primary immune defects deciphered and defeated. PMID- 11213808 TI - The genetic and biochemical basis of Omenn syndrome. AB - Omenn syndrome (OS) is a peculiar, autosomal recessive severe combined immunodeficiency (SCID) associated with early-onset, generalized, exudative erythrodermia; lymphoadenopathy; hepato- and splenomegaly; hypereosinophilia; elevated serum IgE; and normal to high activated, yet non-functional, oligoclonal T cells. Recent investigations have shown that the primum movens of all these puzzling features lies in a defect of the lymphoid-specific V(D)J recombination process. Abnormalities in both alleles of either Rag-1 or -2 genes are found in all OS patients. At variance with T B- SCID, whose Rag mutations represent null alleles, OS mutations maintain a residual recombination activity, allowing limited T-cell receptor gene rearrangements to occur in the thymus. The gene rearrangements are subsequently expanded in the periphery after environmental antigen exposure. Missense mutations detected in OS have been examined in a number of biochemical assays and have contributed to dissect the various functional domains of both Rag-1 and Rag-2 proteins. The examination of a set of mutations occurring in the Rag-1 N-terminal portion has demonstrated that this region plays a fundamental role in vivo. The elucidation of the molecular basis of OS has allowed us to perform early prenatal diagnosis and could be the basis for trials of in utero bone marrow transplantation or gene therapy approaches. PMID- 11213809 TI - Defects in early B-cell development: comparing the consequences of abnormalities in pre-BCR signaling in the human and the mouse. AB - Patients with genetic defects in B-cell development provide an unusual opportunity to dissect the requirements for normal B-cell maturation. It is striking that all of the known genetic defects that result in a failure of B-cell development involve signaling through the pre-B-cell receptor (pre-BCR). Approximately 85% of affected patients are males with mutations in the X chromosome-encoded cytoplasmic tyrosine kinase Btk. Preliminary experiments using stem cell transplants and retroviral-mediated gene therapy in Btk-deficient mice suggest that it may be relatively easy to correct serum immunoglobulins but harder to correct antibody production to T-cell-independent antigens in this disorder. About 3-6% of patients with defects in B-cell development have deletions or critical base pair substitutions in the mu constant region gene. Patients with defects in Igalpha, lambda5 and B-cell linker protein (BLNK) have also been described. All of these patients have a block at the pro-B to pre-B cell transition. Defects in Btk, lambda5 and BLNK result in a more severe phenotype in the human compared to the mouse. These findings suggest that requirements for signaling through the pre-BCR are more stringent in the human compared to the mouse. Possible explanations for this observation are discussed. PMID- 11213810 TI - A brief history of immunodeficiency disease. PMID- 11213812 TI - Molecular basis of IgG subclass deficiency. AB - IgG subclass deficiency was recognized as a separate disease entity in the early seventies and was shown to be associated with an increased susceptibility to infections. Although deletions of the corresponding gamma genes have been demonstrated in a few cases, a majority of patients suffer from a regulatory dysfunction, and the deficiencies are most often relative rather than absolute. Some of the molecular mechanisms underlying the disorder have been unraveled recently. In this review we will touch upon the deletions described within the IGHC locus but mainly concentrate on the regulatory aberrations involved in IgG subclass deficiency. PMID- 11213811 TI - Autosomal primary immunodeficiencies affecting human bone marrow B-cell differentiation. AB - Since the initial report of X-linked agammaglobulinemia by Bruton, numerous autosomal primary immune deficiencies affecting early B-cell differentiation have been described in humans. The identification of these autosomal mutations has been facilitated by phenotype comparison with knockout mice. In mice, defects in B-cell development have been observed after disruption of genes encoding transcription factors, the interleukin-7 pathways as well as structural or signaling components of the pre-B-cell receptor. In general, the phenotypes of primary immune deficiencies in humans correlate with those observed in mutant mice, validating the use of the mouse model approach. In addition, we report a follow-up analysis of an autosomal primary deficiency in a young female patient born from consanguinous parents and characterized by the absence of pre-B and B cell compartments. The patient's gene defect was identified as a cytosine insertion at the beginning of the CH1 exon of the Ig(mu) gene, resulting in a stop codon at position 48 and the absence of Ig(mu) chain expression. The precise phenotype of this patient is compared to other autosomal primary immunodeficiencies affecting humans and mice. PMID- 11213813 TI - Abnormal levels of urokinase plasminogen activator protein and tissue plasminogen activator activity in human aortic aneurysms. AB - OBJECTIVE: To measure the concentrations and activities of plasminogen activators and plasminogen activator inhibitors in human abdominal aneurysms. DESIGN: Laboratory study. SETTING: University hospital, Sweden. MATERIAL: Biopsy specimens from 12 abdominal aortic aneurysms and 8 normal aortas (controls). INTRERVENTIONS: Tissues were homogenised and eluted. The supernatants were assayed for antigens of tissue and urokinase plasminogen activator and plasminogen activator inhibitor 1 and 2. The activities of tissue plasminogen activator and plasminogen activator inhibitor-1 were assayed by ELISA. Frozen sections were immunostained for tissue and urokinase plasminogen activators and for plasminogen activator inhibitor-1. MAIN OUTCOME MEASURES: Concentrations and activities of these activators and inhibitors. RESULTS: The concentration of urokinase plasminogen activator antigen was higher in aneurysmal walls than in normal aortas; it was detected immunohistochemically in aneurysmal but not in normal aortas. The concentration (and the detection immunohistochemically) of tissue plasminogen activator was equal in aneurysmal and normal aortas, but its activity was reduced in the aneurysmal wall. Plasminogen activator inhibitor-1 did not differ significantly between the groups. CONCLUSIONS: Urokinase plasminogen activator may be responsible for the digestion of the media of the aorta and the development of an aneurysm. Reduced activity of tissue plasminogen activator may be responsible for thrombosis in the aneurysm. PMID- 11213814 TI - Advanced breast biopsy instrumentation for the evaluation of impalpable lesions: a reliable diagnostic tool with little therapeutic potential. AB - OBJECTIVE: To assess the potential of advanced breast biopsy instrumentation (ABBI) to clarify the diagnosis of impalpable mammographic lesions and to remove the entire malignant lesions with clear margins. DESIGN: Prospective assessment in a consecutive series of patients. SETTING: University hospital, Basel, Switzerland. SUBJECTS: 139 patients presenting with 144 impalpable microcalcifications or solid nodular densities evident on screening and follow-up mammograms that were suspicious of malignancy. MAIN OUTCOME MEASURES: Feasibility, sensitivity, efficiency in obtaining definitive diagnoses in an outpatient clinic under local anaesthesia, feasibility of complete removal of a primary malignancy, and intervention-related morbidity. RESULTS: The ABBI procedure was successful in 135/144 (94%); an accurate diagnosis was made in 129/130 patients followed up (99%), sensitivity for malignant lesions was 31/32 (97%) and there were 2 complications (2%). Margins of the biopsy cylinder contained a malignant lesion in 26/31 (84%). CONCLUSIONS: Excisional biopsy using the ABBI system is a reliable diagnostic tool with a low morbidity. As in other published series margins were often not clear of tumour and therefore the therapeutic use of the ABBI procedure is limited. PMID- 11213815 TI - Endoscopic sentinel node detection with a gamma probe combined with minimally invasive axillary lymph node dissection: a preliminary study. AB - OBJECTIVE: To investigate the efficacy of videoendoscopic axillary lymph node dissection combined with endoscopic sentinel node detection by gamma probe and preoperative sentinel node imaging. DESIGN: Open study. SETTING: University hospital, Germany. SUBJECTS: Four patients with breast cancer. INTERVENTION: Injection of 99mTc-nanocolloid around the tumour. RESULTS: In three patients axillary sentinel nodes were detected both before and after operation. In the remaining one it was not found. In two patients the minimally invasive approach had to be converted to conventional open surgery because of anatomical restrictions. CONCLUSION: We describe a new approach that uses a minimally invasive technique and endoscopic radioguided sentinel node biopsy in patients with breast cancer. The results of this preliminary study warrant further investigation. PMID- 11213816 TI - Clinical and quality of life outcomes of laparoscopic and open splenectomy for haematological diseases. AB - OBJECTIVE: To study the outcome of open and laparoscopic splenectomy for haematological diseases in terms of quality of life and haematological measures. DESIGN: Prospective non-randomised study. SETTING: Tertiary care hospital, USA. PARTICIPANTS: 44 patients, 27 treated laparoscopically and 17 by open splenectomy. MAIN OUTCOME MEASURES: Quality of life judged by the SF-36 and adequacy of control of the haematological disease. RESULTS: Both quality of life and haematological disease were significantly improved by operation; laparoscopically treated patients had less pain. CONCLUSION: In properly selected patients laparoscopic splenectomy is preferable to open splenectomy. PMID- 11213817 TI - Use of absorbable mesh in the treatment of parenchymal liver injuries during orthotopic liver transplantation. AB - OBJECTIVE: To find out whether packing or wrapping with polyglactin 910 mesh was more effective in stopping bleeding in livers that had been damaged during transplantation. DESIGN: Retrospective study. SETTING: University hospital, Austria. SUBJECTS AND INTERVENTIONS: 15 of 27 livers that had been damaged during transplantation bled sufficiently to warrant either packing (n = 6) or wrapping (n = 9). MAIN OUTCOME MEASURES: Arrest of bleeding; other complications. RESULTS: Both packing and wrapping succeeded in stopping the bleeding, and neither caused infections. Packing may theoretically cause an increase in intra-abdominal pressure and impair organ function. CONCLUSION: It is preferable to wrap rather than pack a bleeding liver that has been damaged during transplantation. PMID- 11213818 TI - Operative treatment of acute complications of diverticular disease: primary or secondary anastomosis after sigmoid resection. AB - OBJECTIVE: To assess the comparative effects of two surgical regimens on the outcome of acute complicated diverticular disease. DESIGN: Retrospective study. SETTING: Teaching hospital, The Netherlands. SUBJECTS: 60 patients who presented with acute complicated diverticular disease. INTERVENTIONS: 28 patient were treated by sigmoid resection and a Hartmann operation, and 32 by resection with primary anastomosis and defunctioning stoma. MAIN OUTCOME MEASURES: Morbidity and mortality. RESULTS: The severity of peritonitis and the amount of faecal contamination were similar in the 2 groups. 12 patients died (7 in the Hartmann group and 5 in the primary anastomosis group). There were 3 radiological leaks with no clinical implications in the primary anastomosis group. 6 patients in the Hartmann group and 5 in the primary anastomosis group required reoperations for intra-abdominal abscess or infection. 7 and 3 patients, respectively, developed dysfunction of their stomas, and 9/21 and 3/27, respectively, required a permanent stoma (p = 0.02, 95% confidence interval of difference 0.07 to 0.56). 3 patients in the Hartmann group developed anastomotic leaks after closure of their stomas, 1 of whom required reoperation but died. No patient developed an anastomotic leak after closure of the stoma in the primary anastomosis group. CONCLUSION: Both regimens are accepted treatments for patients with acute complicated diverticular disease, but because of the higher morbidity after the Hartmann procedure we prefer primary anastomosis with covering stoma. PMID- 11213819 TI - Production of free radicals measured by spin trapping during operations for stenosis of the carotid artery. AB - OBJECTIVES: To analyse production of free radicals during operations for stenosis of the internal carotid artery. SETTING: University hospital, Sweden. SUBJECTS: 10 patients operated on for carotid artery stenosis. INTERVENTIONS: Blood samples were repeatedly drawn from the sigmoid sinus through a catheter in the internal jugular vein on the same side, before, during, and after clamping of the internal carotid artery. OXANOH was added to the blood samples in vitro and the radical production calculated from the amount oxidised to OXANO as electron spin resonance. MAIN OUTCOME MEASURES: The relation between radical production and certain clinical variables investigated by partial least squares regression analysis. RESULTS: There were several significant relations. High systolic blood pressure and advanced age were associated with low, and severe degree of stenosis with increased, free radical production. Certain anaesthetic drugs as well as blood variables also influenced the production of radicals. CONCLUSIONS: The technique used seems to offer the possibility to find and study methods to reduce free radical production during this kind of operation. PMID- 11213820 TI - Morbidity and functional outcome after restorative proctocolectomy for ulcerative colitis. AB - OBJECTIVE: To find out whether a threefold increase in follow up (median 108 compared with 36 months) influenced major morbidity and functional outcome between the first 32 and the last 32 patients consecutively operated on with J pouch ileoanal anastomosis for ulcerative colitis from 1984 to 1997. DESIGN: Retrospective and prospective study. SETTING: University hospital, Norway. PATIENTS: 64 patients with ulcerative colitis who had proctocolectomy and ileal pouch-anal anastomoses. INTERVENTIONS: The pouches were mainly hand anastomosed (n = 61) to the dentate line after mucosectomy or anastomosed by double stapling technique without mucosectomy (n = 3). The 58 patients who still had their pouches responded to a questionnaire on functional outcome and satisfaction. MAIN OUTCOME MEASURES: Morbidity, functional outcome, and patients' satisfaction. RESULTS: Major morbidity in these 64 patients comprised pelvic sepsis in 3 (5%), operation for intestinal obstruction in 5 (8%), pouchitis in 12 (19%), fistulas in 7 (11%) and pouch excision in 6 (9%). Thirteen patients (20%) had 35 reoperations and 11 patients (17%) had 22 re-laparotomies. There were more complications among the first 32 patients with the longest follow up than among the last 32 patients, but this difference was significant only concerning the rate of reoperations (31% compared with 9%) because of the higher number of pouch excisions (5 compared with 1) in this group. There were no significant differences in the functional outcome and degree of patient satisfaction between the first 29 and the last 29 patients. Respective values for 24 hour median stool freqency were 7.0 and 6.3, leakage of stool 48% and 38%, ability to defer defaecation 86% and 97%, perineal irritation 59% and 48%, use of antidiarrhoeal medication 55% and 52%, and wearing of pad 28% and 38%. Sexual life (n = 57) was improved in 11 (19%) and reduced in 7 (12%). Potency was reduced in 5 (15%) and ejaculation in 4 (12%), one of whom (3%) had retrograde ejaculation. Three (5%) received disability pensions and five (9%) had reduced workload. After the pouch operation 48 (91%) felt better and 3 (6%) felt worse because of frequent bowel emptying, perineal eczema, or pouch fistula. CONCLUSION: Continence-preserving proctocolectomy carries considerable morbidity, but the long term functional outcome is satisfactory and does not seem to deteriorate substantially. PMID- 11213822 TI - Monitoring of p53 autoantibodies after resection of colorectal cancer: relationship to operative curability. AB - OBJECTIVE: To investigate the clinical use of p53 autoantibodies as a marker in the postoperative monitoring of colorectal cancer. DESIGN: Retrospective study. SETTING: Teaching hospital, Japan. SUBJECTS: 40 patients with colorectal cancer who had p53 autoantibodies in their serum preoperatively. INTERVENTIONS: Serial assay of p53 autoantibodies by ELISA before and after resection. MAIN OUTCOME MEASURES: Interpretation by a qualitative analysis. RESULTS: A significant correlation was observed between curability by surgical resection and postoperative disappearance of p53 autoantibodies. Twenty-seven (96%) of 28 patients, who had p53 autoantibodies and whose cancer was completely removed, had no such antibodies after resection and no recurrence after 7 to 26 months. CONCLUSIONS: Postoperative assays of p53 autoantibodies are potentially useful for predicting recurrence of colorectal cancer in patients who have p53 autoantibodies preoperatively. PMID- 11213821 TI - Trimethoprim-sulphamethoxazole and metronidazole as prophylaxis in colorectal surgery: a study of bioavailability after an oral single dose. AB - OBJECTIVE: To evaluate oral single dose prophylaxis in colorectal surgery. DESIGN: Prospective study. SETTING: University hospital, Sweden. SUBJECTS: 24 patients (13 women; 11 men; mean age 57 years, range 27-81) listed for elective colorectal operations. INTERVENTION: At 0630 on the day of the operation all patients were given an oral dose of trimethoprim-sulphamethoxazole (TMP 160 mg and SMZ 800 mg) and metronidazole (2 g). The serum concentrations of TMP and SMZ were analysed in venous samples taken at the start and end of each operation. RESULTS: The earliest operation started at 0830 and the last finished at 1700. The median (range) serum concentrations of TMP were 1.4 (0.7-2.6) mg/L (start) and 1.3 (1.0-2.8) mg/L (end), and of SMZ 35 (15-65) mg/L (start) and 33 mg (13 70) mg/L (end). The individual values were above or equal to the minimal inhibitory concentration (TMP 0.8 mg/L; SMZ 15.2 mg/L) for relevant gram-negative species. CONCLUSION: Oral TMP/SMZ in the morning gives satisfactory serum concentrations independently of when the operation is done during the day. The regimen is simple and has the potential for being an effective alternative to intravenous prophylaxis. PMID- 11213823 TI - Somatostatin blockade improves the proliferative response but not intestinal morphological growth after small bowel resection in rats. AB - OBJECTIVE: To find out whether or not blockade of somatostatin improves intestinal adaptation after small bowel resection. DESIGN: Laboratory experiment. SETTING: Teaching hospital, Spain. SUBJECTS: Eighty adult Wistar rats. INTERVENTIONS: Animals underwent intestinal resection or sham operation (n = 40 each) and were treated with a somatostatin antagonist either intermittently or continuously in three different doses (n = 8 each). MAIN OUTCOME MEASURES: Bowel mucosal thickness, proliferation and concentrations of cAMP, somatostatin, insulin-like growth factor 1. RESULTS: Intestinal resection induced a proliferative and morphometric increase of the mucosa; however, the antagonist increased proliferation only in those animals given the highest dose. Intermittent doses induced a proliferative effect that was stronger than that in the three continuous groups. There was no relationship between trophic stimulus and insulin-like growth factor 1 or cAMP, but somatostatin concentrations increased after the intermittent course. CONCLUSIONS: Somatostatin receptor blockade with an antagonist does not cause in normal rats an intestinal morphological adaptation process or increase it after resection; however, it did promote a proliferative stimulus in the crypts. PMID- 11213824 TI - Mass closure technique: an experimental study on separation of wound edge. AB - OBJECTIVE: To study separation of wound edges in midline laparotomy incisions closed with either a mass stitch or a stitch incorporating only aponeurosis. DESIGN: Experimental study in pig. SETTING: University hospital, Norway. ANIMALS: 8 domestic pigs. METHODS: Steel sutures were used and metallic clips were placed in the aponeurosis. After increasing the intra-abdominal pressure the distance between the lateral edge of stitches and between pairs of clips was measured on sequential radiographs. RESULTS: After three hours with raised intra-abdominal pressure the lateral edge of stitches became separated by a mean (SD) of 5.6 (1.3) mm with a mass stitch and by 0.5 (0.6) mm with stitches placed only in the aponeurosis (p < 0.001). Corresponding figures for separation of clips was 3.6 (1.5) mm and 0.1 (0.3) mm (p < 0.001). The suture cut through the muscle by more than 3mm in 25 out of 36 mass stitches. Muscle and peritoneum included in the mass stitch was compressed, darkly discoloured, and there were signs of haemorrhage. CONCLUSIONS: Wound edges become separated with a mass stitch but not with stitches placed only in the aponeurosis when the intra-abdominal pressure is raised after closure of midline laparotomy incisions. This results from sutures compressing or cutting through subcuticular fat, muscle, and peritoneum enclosed in a mass stitch. PMID- 11213825 TI - Internal jugular vein invasion by thyroid carcinoma. PMID- 11213826 TI - Surgical management of pancreatic sarcoid. PMID- 11213828 TI - Umbilical herniorrhaphy in cirrhotic patients: a safe approach. PMID- 11213827 TI - Splenic salvage by superselective embolisation after blunt abdominal trauma. PMID- 11213829 TI - Laparoscopic management of common bile duct stones. PMID- 11213830 TI - Gastrointestinal stromal tumors--definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. AB - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. They are defined here as KIT (CD117, stem cell factor receptor)-positive mesenchymal spindle cell or epithelioid neoplasms primary in the GI tract, omentum, and mesentery. GISTs typically present in older individuals and are most common in the stomach (60-70%), followed by small intestine (20-25%), colon and rectum (5%), and esophagus (<5%). Benign tumors outnumber the malignant ones by a wide margin. Approximately 70% of GISTs are positive for CD34, 20-30% are positive for smooth muscle actin (SMA), 10% are positive for S100 protein and <5% are positive for desmin. The expression of CD34 and SMA is often reciprocal. GISTs commonly have activating mutations in exon 11 (or rarely exon 9 and exon 13) of the KIT gene that encodes a tyrosine kinase receptor for the growth factor named stem cell factor or mast cell growth factor. Ligand-independent activation of KIT appears to be a strong candidate for molecular pathogenesis of GISTs, and it may be a target for future treatment for such tumors. Other genetic changes in GISTs discovered using comparative genomic hybridization include losses in 14q and 22q in both benign and malignant GISTs and occurrence in various gains predominantly in malignant GISTs. GISTs have phenotypic similarities with the interstitial cells of Cajal and, therefore, a histogenetic origin from these cells has been suggested. An alternative possibility, origin of pluripotential stem cells, is also possible; this is supported by the same origin of Cajal cells and smooth muscle and by the common SMA expression in GISTs. GISTs differ clinically and pathogenetically from true leiomyosarcomas (very rare in the GI tract) and leiomyomas. The latter occur in the GI tract, predominantly in the esophagus (intramural tumors) and the colon and rectum (muscularis mucosae tumors). They also differ from schwannomas that are benign S100-positive spindle cell tumors usually presenting in the stomach. GI autonomic nerve tumors (GANTs) are probably a subset of GIST. Other mesenchymal tumors that have to be separated from GISTs include inflammatory myofibroblastic tumors in children, desmoid, and dedifferentiated liposarcoma. Angiosarcomas and metastatic melanomas, both of which are often KIT-positive, should not be confused with GISTs. PMID- 11213831 TI - The association between tumour progression and vascularity in myxofibrosarcoma and myxoid/round cell liposarcoma. AB - Angiogenesis is an important factor in the morphological progression and metastasis of many solid tumours. We studied two homogeneous series of myxofibrosarcoma (MFS) and myxoid/round liposarcoma (MRLS), characterised by distinct vascular patterns and correlated the intratumoral microvessel density (IMD) with morphologic progression in both types of sarcoma. In our study, 43 cases of MFS and 42 cases of MRLS were graded according to established diagnostic criteria. For evaluation of IMD, representative sections were stained immunohistochemically for CD31. After selection of "neovascular hot spots", IMD was calculated by measuring the endothelial surface within twenty 200x fields in relation to the total analysed area. In addition to the correlation of IMD with histological grades of malignancy, a correlation of IMD with the inflammatory infiltrate in MFS was done. To determine whether vascular endothelial growth factor (VEGF) and its receptors, KDR and flt-1, may play a role in the progression of both types of sarcomas, we used mRNA in situ hybridisation (ISH) to study VEGF, KDR and flt-1 expression in selected cases. In addition, the expression of thrombospondin-1, which has been reported to inhibit angiogenesis, and of collagen type I was studied using mRNA ISH. Cases of MFS varied histologically from hypocellular, mainly myxoid, neoplasms (low-grade malignant, 18 cases) to intermediate-grade malignant lesions with increased cellularity and mitotic activity (13 cases), and high-grade malignant cases with marked pleomorphism, high proliferative activity and areas of necrosis in many cases (12 cases). Cases of purely low-grade myxoid liposarcoma (16 cases) were characterised by low-cellularity, mucin pooling and plexiform vasculature. In combined MRLS, these hypocellular areas were admixed with hypercellular, round cell areas (5-80% of the analysed tumour area; 23 cases), and in round cell liposarcoma (three cases) rounded tumour cells predominated (>80% of the analysed tumour area). The average IMD in intermediate and high-grade malignant MFS (4.03 and 4.09, respectively) was significantly higher than in low-grade malignant MFS (2.73). Correlation of vascularity with the inflammatory infiltrate in MFS showed increased IMD only in cases with abundant neutrophils; most of these cases were high-grade malignant neoplasms. In contrast, no statistical correlation between morphological progression and IMD was seen in myxoid liposarcoma (6.08), MRLS (6.57) and round cell liposarcoma (4.07). VEGF mRNA was expressed by tumour cells in all histological grades of MFS and MRLS. VEGF receptor mRNA was weakly expressed by endothelia of newly formed blood vessels in both entities. Interestingly, tumour cells of all analysed cases of MFS strongly expressed collagen type I and thrombospondin-1, while these proteins were not detected in tumour cells of MRLS. In conclusion, morphologic tumour progression in MFS is associated with increased IMD, whereas, in MRLS, no such correlation is seen. Whereas VEGF and VEGF receptor mRNA were expressed in both entities, a characteristic expression profile of collagen type I and thrombospondin-1 in MFS emerged. Further studies are necessary to correlate vascularity and clinical course in MFS and MRLS. PMID- 11213832 TI - Expression of cadherins and their undercoat proteins (alpha-, beta-, and gamma catenins and p120) and accumulation of beta-catenin with no gene mutations in synovial sarcoma. AB - E-cadherin, the major intercellular adhesion molecule of epithelial cells, is important in determining the architecture of sarcomas, especially those showing epithelioid features. In addition to its role in cell adhesion, beta-catenin, a cadherin undercoat protein, has been shown to function as a downstream transcriptional activator of the Wnt/Wingless signaling pathway. In order to evaluate the significance of the cadherin cell adhesion system and the Wnt/Wingless signaling pathway in the morphogenesis and/or tumorigenesis of synovial sarcoma (a major type of sarcoma with epithelioid features), immunoreactivity for pan-cadherin, E-cadherin, and their undercoat proteins (alpha-, beta-,and gamma-catenins and p120) was evaluated in 15 synovial sarcomas. Immunoreactivity for pan-cadherin, E-cadherin, alpha-catenin, beta catenin, and p120 was observed in all 15 specimens. Immunoreactivity for pan cadherin was stronger than that for E-cadherin. Expression of gamma-catenin was detected in ten specimens. Although beta-catenin was observed only at the cell cell boundaries in four specimens, it was present in the nucleus and cytoplasm and at the cell-cell boundaries in the other 11, suggesting constitutional activation of the Wnt/Wingless signaling pathway in synovial sarcoma. Direct sequencing for exon 3 of the beta-catenin gene, however, revealed no mutations in any of the 15 specimens. In conclusion, other types of cadherin besides E cadherin, together with cadherin undercoat proteins, may play a role in cell adhesion in synovial sarcoma. Furthermore, mechanisms other than mutation of exon 3 of the beta-catenin gene may activate the Wnt/Wingless signaling pathway in this type of tumor. PMID- 11213833 TI - Evidence for two modes of allelic loss: multifocal analysis on both early and advanced gastric carcinomas. AB - To assess the extent and the timing of allelic loss required for the progression of gastric carcinoma, the intratumoral distribution of loss of heterozygosity (LOH) was compared in early and advanced tumors: early loss is uniformly observed in all tumor areas and late loss is localized in parts of tumor tissue. Tumor sites (167 sites) obtained from 42 gastric carcinoma tissues (26 advanced cancers and 16 early cancers) were examined for LOH on chromosomes 5q, 9p, 13q, 17p, and 18q. By using two or three microsatellite markers for each chromosome arm, it was shown that of 29 tumors showing LOH in at least one tumor site, 15 (51.7%, 12 advanced and three early cancers) harbored multiple losses on three or more chromosome arms, and 89.4% (84 of 94) of these losses was uniformly found in all tumor sites tested. In the remaining 14 tumors (48.3%, eight advanced and six early tumors) with sporadic losses on one or two chromosome arms, 44% (11 of 25) of the losses were commonly shared among the sites tested. Such marked difference (P<0.001, Fisher's exact test) in the intratumoral distribution of multiple and sporadic LOH patterns proposes two distinct LOH subtypes: multiple losses (high LOH), occurring at an early stage with a few additional losses, and sporadic losses (low LOH), taking place relatively late during tumor progression. The multifocal LOH findings imply that, rather than being gradual, the allelic losses take place in two manners that are already determined at an early stage. PMID- 11213834 TI - Immunohistochemical pattern of hMSH2/hMLH1 in familial and sporadic colorectal, gastric, endometrial and ovarian carcinomas with instability in microsatellite sequences. AB - Alterations of DNA mismatch repair (MMR) genes are involved in carcinogenesis of sporadic and inherited human cancers characterised by instability of DNA microsatellite sequences (MSI). MSI tumours are usually identified using molecular analysis. In the present investigation, hMLH1 and hMSH2 immunohistochemistry was tested in order to evaluate the utility of this method in predicting MMR deficiency. Colorectal (72), gastric (68), endometrial (44) and ovarian (17) carcinomas were independently evaluated for familial history, histological type of tumour, MSI status and immunohistochemical results. Loss of expression of either hMLH1 or hMSH2 was observed in 51 of 55 (92.8%) MSI tumours, while 145 of 146 microsatellite stable (MSS) tumours expressed both the hMLH1 and hMSH2 gene products. Independently of tumour site, an overall agreement between immunohistochemical and molecular results was observed in 15 hereditary non polyposis colorectal cancer-related tumours. Among sporadic tumours, only 2 of 60 colorectal and 2 of 66 gastric carcinomas, displaying MSI, expressed both hMLH1 and hMSH2 gene products. All 39 endometrial and 16 ovarian tumours presented a concordant molecular and immunohistochemical profile. These data show that immunohistochemistry is an accurate and rapid method to predict the presence of defective DNA MMR genes and to identify both sporadic and familial MSI tumours. PMID- 11213835 TI - Time-dependent expression of intestinal phenotype in signet ring cell carcinomas of the human stomach. AB - Signet ring cell carcinomas of the stomach are thought to arise from the proper gastric mucosa without intestinal metaplasia. It was recently reported that intestinal phenotypes appear along with tumor progression. In this study, we performed several experiments to reconsider the significance of this intestinalization in the growth of signet ring cell carcinoma. We applied mucin histochemistry with monoclonal antibodies MUC2 (Ccp58) and M1 (45M1), and paradoxical concanavalin A staining for class III mucin [PCS(III)] reaction to 29 intramucosal and 25 deeply invasive carcinomas of this type and correlated the phenotypic expression with the size of the mucosal spread and the depth of tumor invasion. It was found that the larger the size of the mucosal lesion, the more frequently the intestinal phenotypes were demonstrated. There was no significant increase in the expression of the intestinal phenotype as the tumor invaded the deeper part of the mucosa or as the intestinal metaplasia increased in the background mucosa. The intestinal expression appeared to be suppressed in the earlier phase of deep invasion. In the mucosal part of the tumor, the intestinal phenotype was often expressed regionally and incompletely, coexisting with gastric phenotypes at the cellular and the tissue levels. These findings indicate that the expression of the intestinal phenotype is a time-dependent and unstable phenomenon probably based on the accumulation of genetic changes and plays a neutral role in progression of signet ring cell carcinomas. PMID- 11213836 TI - Gains of 12q13-14 and overexpression of mdm2 are frequent findings in intimal sarcomas of the pulmonary artery. AB - The characterization of clinical, histopathological, immunohistochemical, and genetic features of intimal sarcomas arising in the pulmonary artery is presented in this study. Four resected lungs, one endarterectomy specimen and three biopsies from eight patients (four males and four females; median age 41 years) suffering from intimal sarcomas of the pulmonary artery using conventional stains, immunohistochemistry, and comparative genomic hybridization (CGH) were analyzed. The predominant clinical presentation was dyspnea (all eight patients) and febrile pulmonary disease (six of eight). Signs of embolic lung disease were present in all patients. One patient died postoperatively, six patients died of disease 8-35 months after presentation, and one patient was alive 6 months after surgery. Histopathological examination of the submitted material showed spindle cell, partially myxoid and pleomorphic sarcomas. Metastases were histologically confirmed in three patients (lung, pleura, and skull). Immunohistochemically, vimentin was strongly expressed in all tumors. Focal positivity was observed for alpha smooth muscle actin, CD117, CD68, p53, and bcl2. No reaction could be obtained for endothelial markers. The proliferation index Ki-67 was between 5% and 80%. Six examined tumors were positive for mdm2. In the CGH analysis, gains and amplifications in the 12q13-14 region were found in six of eight tumors (75%). Other, less consistent alterations, were losses on 3p, 3q, 4q, 9p, 11q, 13q, Xp, and Xq, gains on 7p, 17p, and 17q, and amplifications on 4q, 5p, 6p, and 11q. Intimal sarcomas of the pulmonary artery are tumors with an unfavorable prognosis and poorly differentiated morphology. A majority of tumors show a consistent genetic alteration (gains and amplifications in the 12q13-14 region) and overexpression of mdm2, implicating the mdm2/p53 pathway as a possible mechanism in the tumor pathogenesis. PMID- 11213837 TI - Angiomyxolipoma shares cytogenetic changes with lipoma, spindle cell/pleomorphic lipoma and myxoma. AB - Angiomyxolipoma is a rare variant of lipoma, two cases of which have recently been described. We report on the hitherto unreported clonal chromosomal changes of a third case of angiomyxolipoma. The karyotype showed a 46,XX,t(7;13)(p15;q14),t(8;12)(q13;p13)[17]/46,XX[3]. The involvement of 13q14, 12p13, and 8q13 supports a relationship with other types of benign lipomatous and myxoid tumors. PMID- 11213838 TI - Expression of monocyte chemoattractant protein-1 in peritoneal endometriotic cells. AB - It is well known that the number of peritoneal macrophages is increased in patients with pelvic endometriosis. We measured the concentration of monocyte chemoattractant protein-1 (MCP-1) using an enzyme-linked immunosorbent assay (ELISA) in the peritoneal fluid of women with and without endometriosis. The expression of MCP-1 in pelvic endometriotic lesions obtained from the peritoneum was also examined using immunohistochemistry and nonradioactive in situ hybridization. The mean concentration of MCP-1 in the peritoneal fluid was significantly higher in the patients with endometriosis (P<0.05). The most significant elevation, compared with non-endometriosis patients, was found in stage I of the disease (P<0.05). However, no statistically significant difference was found among endometriosis stages I, II, III, and IV. Immunohistochemical staining revealed that MCP-1-positive cells were localized in the glandular epithelium of the endometriotic lesions and in the stromal macrophages distributed in those lesions, but normal peritoneal cells were negative. The in situ hybridization method demonstrated expression of MCP-1 mRNA on the endometriotic glandular epithelium and stromal macrophages. These findings suggest that MCP-1 may be involved in the histogenesis and early development of peritoneal endometriosis. PMID- 11213839 TI - Alteration of CD44 and cadherins expression: possible association with augmented aggressiveness and invasiveness of endometrial carcinoma. AB - Cadherins and CD44 isoforms are transmembrane glycoproteins with diverse functions in cell-cell and cell-matrix interactions and may be a determinant of invasive and metastatic behavior in carcinomas. The immunohistochemical expression of cadherins and CD44 in tissue samples from 15 normal endometrium and 33 endometrial adenocarcinomas were examined. The immunohistochemical analysis was performed using the monoclonal antibody HECD-1 against E-cadherin and the polyclonal antibody against N-cadherin. In addition, the monoclonal antibodies 2C5, which binds to CD44s and all of the variants encoded by exons 3-10; 3G5, which is specific for CD44v3; and 2F10, which is specific for CD44v6 were used. E cadherin (P=0.0001) and N-cadherin (P<0.001) expressions were statistically lower in endometrial adenocarcinoma than in normal endometrium. In contrast, an overexpression of CD44 isoforms (P<0.01) and CD44v3 (P<0.01) expressions was found in endometrial adenocarcinomas compared with normal endometrium. No difference was noted for CD44v6. An association was found between a decrease in E cadherin expression and the occurrence of local recurrent and nodal metastasis. An association was found between CD44 overexpression, lymph space involvement, and myometrial invasion. Our results suggest that cadherin and CD44 expressions in endometrial carcinomas may have a prognostic value. Alteration of CD44 seems to be related to local invasion, while alteration of E-cadherin seems to be associated with dissemination of the disease. PMID- 11213840 TI - Immunohistochemical analysis of the proliferative activity of neuroendocrine tumors from various organs. Are there indications for a neuroendocrine tumor carcinoma sequence? AB - Small-cell neuroendocrine carcinomas (NECs) of the prostate are believed not to derive from benign orthotopic NE epithelial cells. Instead, an origin from a putative stem cell is actually the most favored concept. Whether this concept can also be applied to neuroendocrine tumors (NETs) of other organs, especially whether there are indications for well-differentiated NET-NEC sequence, is subject of the present study. A double-labeling technique for the proliferation marker MIB-1 and the NE markers chromogranin A (ChrA) and synaptophysin (SNP) was used for the immunohistochemical analysis of 45 well-differentiated NETs, 16 well differentiated (low-grade) NECs, and 63 high-grade NECs of the esophagus, stomach, small intestine, appendix, colon, lung, prostate, and urinary bladder. The lowest proliferative activity was found in NETs (0.85% of tumor cells), and the highest activity was found in high-grade NECs (72.5%). The expression of ChrA was highest in NETs and lowest in high-grade NECs. None of the NETs and only sporadic cells in low-grade NECs showed double labeling (up to 0.05%). Up to 50% of the tumor cells in high-grade NECs were positive for MIB-1 and SNP. The percentage of double-labeled cells ranged between 0.9 and 39.6 (mean 9.7). No double-labeled cells were found in the normal epithelium adjacent to the tumors. Transitions from NET to NEC could not be observed. NETs and low-grade NECs differ in their proliferative activity from high-grade NECs, suggesting that they may arise from different precursor cell populations. PMID- 11213841 TI - Volume-weighted mean nuclear volume and numerical nuclear density in the cardiomyocyte following enalapril and verapamil treatment. AB - The estimation of the volume-weighted mean nuclear volume, nu(nu), and the numerical nuclear density in the plane, N(A), was used to analyze cardiomyocyte nuclei in the condition of cardiac hypertrophy caused by nitric oxide (NO) synthesis blockade and simultaneous antihypertensive treatment for 40 days (four groups of ten rats each: control, L-NAME, L-NAME+enalapril, L-NAME+verapamil). The blood pressure (BP) increased 71% in the L-NAME group. In the L NAME+enalapril and L-NAME+verapamil groups, the BP did not show any alteration when compared with the respective controls. In comparison with the control group, nu(nu) was 250% greater, and the N(A) was 25% smaller in the L-NAME animals, while no difference occurred in the other two groups. With respect to cardiomyocyte nuclear size, the present results suggest a beneficial effect of the angiotensin-converting enzyme inhibitor enalapril and the calcium channel blocker verapamil when NO synthesis is blockaded. PMID- 11213842 TI - Personality disorders in the community: a report from the Australian National Survey of Mental Health and Wellbeing. AB - BACKGROUND: The first set of aims of the present study was to determine the prevalence of personality disorders (PDs) in a nation, and gender differences in the types and numbers of PDs endorsed. The second set of aims was to establish the relationship of PD to other, non-PD disorders, physical conditions, and disability. METHOD: Data were obtained from the Australian National Survey of Mental Health and Wellbeing, conducted between May and August 1997. A stratified random sample of households was generated, from which all those aged 18 or over were considered potential interviewees. There were 10,641 respondents to the survey, and this represented a response rate of 78%. Each interviewee was asked 59 questions indexing specific ICD-10 PD criteria. RESULTS: Of the total survey sample, 704 persons had at least one PD. Using weighted replicate weights, it was estimated that approximately 6.5% of the adult population of Australia have one or more PDs (lifetime prevalence). Persons with PD were more likely to be younger, male, and not married, and to have an anxiety disorder, an affective disorder, a substance use disorder, or a physical condition. They were also more likely to have greater disability than those without PD. CONCLUSION: The study is the first nationwide survey of mental disorders conducted within Australia. It provides an estimate of the prevalence of the various types of PD. The survey has considerable limitations, however, and these are discussed. PMID- 11213843 TI - Prevalence of alcohol consumption, abuse and dependence in a country with high per capita consumption: findings from the German TACOS study. Transitions in Alcohol Consumption and Smoking. AB - BACKGROUND: The aim of the Transitions in Alcohol Consumption and Smoking (TACOS) project is to investigate substance use and use disorders in the adult general population in a region of the under-researched north of Germany, focussing on smoking and alcohol consumption. In this study, the design and quality assurance provisions of the baseline cross-section of the longitudinal project are described. Prevalence rates of alcohol use disorders, consumption pattern, and the nature of their association are also analysed with regard to preventive strategies. METHOD: A random sample of 4075 participants, aged 18 to 64 and drawn from residents registration office files, was interviewed with a DSM-IV adapted version of WHO CIDI. Fieldwork resulted in a response rate of 70.2% and an unbiased database with regard to demographic characteristics. RESULTS: Low lifetime prevalence of alcohol use disorders (4.5% abuse, 3.8% dependence) and hazardous consumption (13.2% lifetime; 6.0% 12-month) was found compared to southern regions of Germany and US American data. In contrast, we found a comparatively high percentage of moderate alcohol uses. Male subjects are more affected by lifetime alcohol use disorders (abuse OR 8.3, 95% CI 5.3-13.2; dependence OR 4.3, 95% CI 2.8-6.4). The association between alcohol use disorders and alcohol consumption pattern revealed a weaker relation for alcohol abuse compared to dependence. CONCLUSION: National and regional drinking habits and norms have to be considered as a significant source of variance, supporting the need for European epidemiological research on substance use in addition to US American activities, and emphasising the advantages of community-based preventive measures. An evaluation of public recommendations for safe limits of alcohol consumption and prevention targets referring to average consumption is indicated. There is also a need for a clear distinction between alcohol abuse and dependence. PMID- 11213844 TI - Al Ain Community Survey of Psychiatric Morbidity III. The natural history of psychopathology and the utilization rate of psychiatric services in Al Ain. AB - BACKGROUND: We evaluated the natural history of psychopathology in a stratified sample (n = 245) comprising subjects with no DSM-III-R psychiatric disorder, subthreshold disorder and threshold (DSM-III-R) psychiatric disorder, respectively, over a 12-months period, using the Structured Clinical Interview for DSM-III-R mental disorders (SCID) as an assessment tool. METHODS: A representative sample categorized 1 year earlier into DSM-III-R psychiatric disorder, subthreshold disorder and no DSM-III-R psychiatric disorder were reassessed with SCID 1 year on. The incidence, recovery rates and the percentage of subthreshold disorders which become DSM-III-R disorders were calculated. The utilization rate of psychiatric services was also assessed. RESULTS: The incidence rate of new cases was 10.4%. The recovery (remission) rate was 41.5%, and approximately 20% of subthreshold disorders became definitive disorders (DSM III-R) after 1 year. Anxiety disorders tend to have a higher magnitude of temporal stability in comparison with depressive disorders. Male sex and contact with psychiatric services were found to affect the recovery rate. Approximately 13% of the sample had made contact with psychiatric services with no gender differences, but men were significantly more often hospitalized than women. CONCLUSION: Our findings indicate that mental disorders are relatively common. The high incidence rate found in this study is attributed in part to the high negative rate at baseline assessment. Approximately 60% of psychiatric disorders in the community are persistent, and patients with emotional disorder under utilize existing services. PMID- 11213845 TI - Continuity of contact with psychiatric services: immigrant and Australian-born patients. AB - BACKGROUND: Under-representation of ethnic minority groups in psychiatric services has been widely reported in Western nations. The present study examined whether there were differences between immigrant and Australian-born patients in their maintenance of contact with a statewide psychiatric service system. METHODS: Groups were selected on the empirical grounds that they are differently represented in this service system. Employing a form of case-control design, four groups of patients were compared: those born in Australia, the United Kingdom, Southern Europe, and South East/East Asia respectively (n = 79 for each). Groups were identically matched on sex, age, diagnosis (either schizophrenia or bipolar illness) and locality of service. The groups did not differ as to the timing of their first appearance in the 3-year period in which their psychiatric contact was examined. RESULTS: Despite their different representation in the psychiatric service system, the four groups did not differ on measures of continuity of contact. Measures included number of contacts with mental health community services, number of admissions to inpatient wards, length of stay in hospital and the longest interval between any two successive service contacts. CONCLUSIONS: The commonly reported underrepresentation of immigrant groups in the psychiatric service system does not appear to be due to greater discontinuation of contact with services. If the assumption of equal community prevalence of disorder is made, then the observed under-representation may be due to differential rates of access to (that is, initial contact with) psychiatric services. PMID- 11213846 TI - Increasing use of Dutch mental health care: an investigation. AB - BACKGROUND: In the Netherlands, a previous study has shown an increase in the 1 year prevalence of patients in mental health care during the 1990s. Though the number of inpatients decreased, this decrease was far outweighed by a large increase of patients in community care, causing an increase in total year prevalence. The current study aimed at an explanation. METHODS: The Groningen psychiatric case register was used to determine treated incidence and prevalence over a 9-year period for different age groups. RESULTS: Incidence rates proved fairly stable. The increased prevalence was primarily caused by the growing number of existing cases. People had their first encounter with mental health care at an earlier age and remained in care for a larger part of their life. CONCLUSIONS: Results indicate that the accessibility of Dutch mental health care was increased by the implementation of community care. In contrast to other countries, Dutch community care lowered the threshold for mental health care utilization without broadening the target group of mental health services. PMID- 11213847 TI - A trans-cultural comparison of four psychiatric case-finding instruments in a Welsh community. AB - BACKGROUND: Case-finding instruments have been developed for different purposes and in different cultural settings. Four instruments designed to detect psychiatric morbidity in community-based populations were studied in order to compare the performance of instruments from differing sources in a common setting. METHODS: The study was undertaken in a Welsh primary care setting. The Revised Clinical Interview Schedule (CIS-R) was used to define caseness. The instruments studied were the General Health Questionnaire (GHQ), the Mental Health Index (MHI), the Self Reporting Questionnaire (SRQ), and the Shona Symptom Questionnaire (SSQ). Performance was assessed by standard test indices, kappa values, and receiver operating curve analysis. The content of the four instruments was also compared. RESULTS: Sixty-nine adults completed the study. The prevalence of CIS-R caseness in this sample was 45%. No significant differences in case-recognition were found and all instruments had misclassification rates of 10% or less. The instruments showed wide variation in content. Half the items were unique to a single instrument and only three items (sleep, unhappiness and decision making) were shared by three instruments. The most frequent symptom within the total sample, and among cases, was the Zimbabwean concept of 'thinking too much'. CONCLUSIONS: Etic instruments (SRQ and SSQ) performed as well as emic ones (GHQ and MHI) in this setting, despite the wide variation in instrument structure. PMID- 11213848 TI - Interrelationships among mortality rates, drug costs, total cost of care, and length of stay in United States hospitals: summary and recommendations for clinical pharmacy services and staffing. AB - We evaluated interrelationships and associations among mortality rates, drug costs, total cost of care, and length of stay in United States hospitals. Relationships between these variables and the presence of clinical pharmacy services and pharmacy staffing also were explored. A database was constructed from the 1992 American Hospital Association's Abridged Guide to the Health Care Field, the 1992 National Clinical Pharmacy Services database, and 1992 Health Care Finance Administration mortality data. A severity of illness-adjusted multiple regression analysis was employed to determine relationships and associations. Study populations ranged from 934-1029 hospitals (all hospitals for which variables could be matched). The only pharmacy variable associated with positive outcomes with all four health care outcome measures was the number of clinical pharmacists/occupied bed. That figure tended to have the greatest association (slope) with reductions in mortality rate, drug costs, and length of stay. As clinical pharmacist staffing levels increased from the tenth percentile (0.34/100 occupied beds) to the ninetieth percentile (3.23/100 occupied beds), hospital deaths declined from 113/1000 to 64/1000 admissions (43% decline). This resulted in a reduction of 395 deaths/hospital/year when clinical pharmacist staffing went from the tenth to the ninetieth percentile. This translated into a reduction of 1.09 deaths/day/hospital having clinical pharmacy staffing between these staffing levels, or 320 dollars of pharmacist salary cost/death averted. Three hospital pharmacy variables were associated with reduced length of stay in 1024 hospitals: drug protocol management (slope -1.30, p=0.008), pharmacist participation on medical rounds (slope -1.71, p<0.001), and number of clinical pharmacists/occupied bed (slope -26.59, p<0.001). As drug costs/occupied bed/year increased, severity of illness-adjusted mortality rates decreased (slope 38609852, R(2) 8.2%, p<0.0001). As the total cost of care/occupied bed/year increased, those same mortality rates decreased (slope -5846720642, R(2) 14.9%, p<0.0001). Seventeen clinical pharmacy services were associated with improvements in the four variables. PMID- 11213849 TI - Epidemiology, resistance, and outcomes of Acinetobacter baumannii bacteremia treated with imipenem-cilastatin or ampicillin-sulbactam. AB - STUDY OBJECTIVE: To evaluate epidemiology, resistance, and treatment outcomes of Acinetobacter baumannii bacteremia treated with imipenem-cilastatin or ampicillin sulbactam for 72 hours or longer. DESIGN: Retrospective analysis. SETTING: University teaching hospital. PATIENTS: Forty-eight patients with A. baumannii bacteremia. INTERVENTION: Evaluation of susceptibility and clinical data from 48 patients treated with either ampicillin-sulbactam or imipenem-cilastatin from 1987-1999. MEASUREMENTS AND MAIN RESULTS: Comparing ampicillin-sulbactam and imipenem-cilastatin, there were no differences between days of bacteremia (4 vs 2 days, p=0.05), days to resolution of temperature or white blood cell count, success or failure during or at end of treatment, or intensive care unit total or antibiotic-related length of stay (13 vs 10 days, p=0.05). Patients treated with ampicillin-sulbactam had significantly decreased antibiotic treatment costs (1500 dollars vs 500 dollars, p=0.004). CONCLUSION: Ampicillin-sulbactam is at least as effective as imipenem-cilastatin based on clinical response at days 2, 7, and end of treatment and is a cost-effective alternative for treatment of A. baumannii infections. PMID- 11213850 TI - Influence of coadministration of fluoxetine on cisapride pharmacokinetics and QTc intervals in healthy volunteers. AB - STUDY OBJECTIVE: To evaluate the effect of fluoxetine on the pharmacokinetics and cardiovascular safety of cisapride at steady state in healthy men. DESIGN: Open label, three-phase, sequential study. SETTING: Clinical research center. SUBJECTS: Twelve healthy male volunteers. INTERVENTIONS: Each subject was treated according to the following sequence: baseline; phase 1 (days 1-6): cisapride 10 mg 4 times/day; washout (days 7-13); phase 2 (days 14-44): fluoxetine 20 mg/day; and phase 3 (days 45-52): cisapride 10 mg 4 times/day (days 45-51) plus fluoxetine 20 mg/day (days 45-52). MEASUREMENTS AND MAIN RESULTS: Blood samples were drawn and 12-lead electrocardiograms performed at specified time points after the last morning dose of cisapride in phases 1 and 3. Blood samples also were taken before morning doses on the 3rd, 4th, and 5th days of phases 1 and 3. Electrocardiograms were done at baseline and on the last day of the washout period and phase 2. Coadministration of fluoxetine significantly decreased cisapride plasma concentrations. There were no clinically significant changes in corrected QT intervals during administration of cisapride alone or with fluoxetine. Cisapride was well tolerated when administered alone or with fluoxetine. CONCLUSION: Cisapride can be administered safely to patients receiving low therapeutic dosages of fluoxetine. PMID- 11213851 TI - Relative bioavailability of lamotrigine chewable dispersible tablets administered rectally. AB - STUDY OBJECTIVE: To determine the relative bioavailability of lamotrigine (LTG) chewable dispersible tablets after rectal administration. DESIGN: Two-period, crossover study with a 2-week washout between dosing periods. SETTING: Clinical research center. PATIENTS: Twelve healthy adult volunteers. INTERVENTION: One hundred milligrams of a LTG chewable dispersible tablet was administered by oral and rectal routes. MEASUREMENTS AND MAIN RESULTS: Plasma samples were collected before and up to 120 hours after drug administration. The samples were analyzed for LTG by high-performance liquid chromatography, and the relative bioavailability was determined. Drug concentrations were lower after rectal than after oral administration. The relative bioavailability (F = AUC(rectal)/AUC(oral)) was 0.52 +/- 0.23 (SD). CONCLUSION: Drug prepared from LTG chewable dispersible tablets is absorbed rectally, although not to the same extent as when given orally. Rectal administration of suspension of these tablets can be an acceptable route of administration. PMID- 11213852 TI - Lack of effect of a single dose of ketoconazole on the pharmacokinetics of citalopram. AB - STUDY OBJECTIVE: To determine whether the pharmacokinetics of the antidepressant citalopram are affected by ketoconazole, a potent inhibitor of cytochrome P450 (CYP) 3A4. DESIGN: Single-center, double-blind, randomized, three-way crossover trial. SETTING: Research facility. PARTICIPANTS: Eighteen healthy male and female volunteers. INTERVENTION: Subjects received three treatments with a 14-day washout period: single dose of ketoconazole 200 mg plus placebo, single dose of citalopram 40 mg plus placebo, and single dose of ketoconazole 200 mg plus single dose of citalopram 40 mg. MEASUREMENTS AND MAIN RESULTS: Pharmacokinetic parameters were determined after each treatment. The pharmacokinetic profile of citalopram administered alone was essentially identical to that when administered with ketoconazole. Similarly, the pharmacokinetics of the metabolite desmethylcitalopram were unaltered by ketoconazole. CONCLUSION: No changes in pharmacokinetics of citalopram were observed after coadministration of ketoconazole, suggesting that ketoconazole and other CYP3A4 inhibitors may be administered safely with citalopram. Furthermore, no adjustment of citalopram dosage should be necessary in most patients who receive the drug in combination with a CYP3A4 inhibitor. PMID- 11213853 TI - The pharmacokinetics of subcutaneous enoxaparin in end-stage renal disease. AB - STUDY OBJECTIVE: To evaluate the pharmacokinetics of enoxaparin in end-stage renal disease (ESRD), and determine if dosage reduction is necessary to maintain antifactor Xa activity concentrations within the therapeutic range. DESIGN: Prospective, single-dose pharmacokinetic study. SETTING: University-affiliated general clinical research center. PATIENTS: Eight nonthrombosed patients with ESRD requiring hemodialysis. INTERVENTION: All subjects received a single dose of enoxaparin sodium 1 mg/kg subcutaneously and had serial plasma antifactor Xa activity concentrations measured over 24 hours. MEASUREMENTS AND MAIN RESULTS: The pharmacokinetics of enoxaparin were determined from plasma antifactor Xa activity concentrations, and various multiple-dose regimens were simulated. After administration of the drug, total body clearance was 14.6 ml/minute and there was a 2-fold prolongation in antifactor Xa activity half-life compared with values reported in healthy subjects. All other pharmacokinetic parameters were similar to those in healthy subjects and patients with chronic renal insufficiency. An accumulation ratio of 1.6 was estimated for a dosing interval of every 12 hours based on single-dose pharmacokinetics. When various therapeutic regimens were simulated to predict average steady-state antifactor Xa activity, standard enoxaparin dosages of 1 mg/kg subcutaneously every 12 hours and 1.5 mg/kg every 24 hours resulted in average steady-state concentrations within the therapeutic range. CONCLUSIONS: Based on antifactor Xa activity, ESRD has little effect on the pharmacokinetics of enoxaparin, and dosing adjustments are unnecessary. PMID- 11213854 TI - Evaluation and survey of intravenous vitamin K1 for treatment of coagulopathy in critically ill patients. AB - STUDY OBJECTIVES: To determine patient factors associated with coagulopathy, to assess variables affecting response to vitamin K1, to describe vitamin K1 associated adverse reactions, and to survey Canadian tertiary care hospitals about vitamin K1 practice patterns in their intensive care units (ICUs). DESIGN: Retrospective chart audit and prospective survey. SETTING: Medical-surgical ICU with a 23-bed complement in a tertiary care, university-affiliated hospital, and 47 Canadian tertiary care hospitals. PATIENTS: Forty-eight critically ill patients with nonconsumptive coagulopathies. INTERVENTION: Intravenous vitamin K1 utilization over 4 months. MEASUREMENTS AND MAIN RESULTS: The only independent risk factor for elevated baseline international normalized ratios (INRs) was Acute Physiologic and Chronic Health Evaluation (APACHE) II score (r2 = 0.51, p<0.05). The INR values decreased after two doses of vitamin K1 10 mg for patients grouped as a whole (2.14 +/- 0.96 to 1.61 +/- 0.62, p<0.0001) and when patients were stratified according to APACHE II scores below 23 (1.83 +/- 0.44 to 1.34 +/- 0.18, p<0.05). The INRs were not significantly reduced for patients with APACHE II scores of 23 or greater (2.44 +/- 1.23 to 1.82 +/- 0.66). No variables were associated with response, and adverse events were not observed. Of 47 Canadian tertiary care hospitals surveyed, 27 (55%) responded. Twenty-four (89%) indicated that vitamin K1 was administered intravenously, and no adverse events resembling anaphylaxis were reported. CONCLUSION: Administration of two doses of intravenous vitamin K1 10 mg was associated with reversal of coagulopathies, but variable responses may be expected for patients with high APACHE II scores. Randomized, placebo-controlled studies are necessary to confirm the effectiveness of vitamin K1. PMID- 11213855 TI - Factors associated with the risk of liver enzyme elevation in patients with type 2 diabetes treated with a thiazolidinedione. AB - STUDY OBJECTIVE: To characterize frequency of liver enzyme elevation in patients with type 2 diabetes mellitus receiving troglitazone. DESIGN: Retrospective study. SETTING: Hospital-affiliated medical center. PATIENTS: Two hundred ninety one patients with type 2 diabetes mellitus. INTERVENTION: Data from patients with an average troglitazone exposure of 412.7 +/- 255.6 days were studied. MEASUREMENTS AND MAIN RESULTS: Enzyme elevations more than 1.5 times the upper limit of normal (ULN) occurred in 17 patients (5.8%) and more than 3-fold elevations in 6 (2.1%). The relationship among enzyme elevation events, demographic factors, duration of troglitazone exposure, frequency of monitoring, and concurrent drugs (limited to glucose and lipid-lowering agents) was assessed by multiple logistic regression. Age was an independent predictor of risk (p=0.009), and concurrent insulin therapy approached statistical significance (p=0.051) for 1.5-fold ULN elevation in liver enzymes. Age and concurrent therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors were the only significant predictors of 3-fold ULN elevations (p=0.03 and p=0.04, respectively). CONCLUSION: Several factors appear to increase the risk of enzyme elevation events in patients treated with troglitazone. PMID- 11213856 TI - Improved health-related quality of life with SSRIs and other antidepressants. AB - STUDY OBJECTIVE: To document the health-related quality of life (HRQOL) of depressed patients receiving antidepressant drugs. DESIGN: Cross-sectional study. SETTING: Community pharmacy-based setting. PATIENTS: Fifty-seven depressed patients. INTERVENTION: Independent pharmacist members of the Community Pharmacists Research Network in Georgia administered the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) to subjects. MEASUREMENTS AND MAIN RESULTS: Sixty-one percent of patients were treated with a selective serotonin reuptake inhibitor (SSRI) and 38.6% were treated with a non-SSRI. Those receiving SSRIs scored higher on the mean physical (PCS) and mental (MCS) health summary scores of the SF-36 than those not receiving the drugs. No significant differences were seen in PCS or MCS scores of men and women. CONCLUSION: Community pharmacists documented better HRQOL in patients receiving SSRIs than in those given other antidepressants. PMID- 11213857 TI - A review of budesonide inhalation suspension in the treatment of pediatric asthma. AB - Asthma is recognized as an inflammatory disease, and inhaled corticosteroids are the mainstay of treatment in patients with persistent disease. Until recently, no inhaled corticosteroid was approved in the United States for children aged 4 years and younger, and no practical dosage form was available for infants and young children unable to use metered-dose inhalers effectively. Budesonide inhalation suspension (BIS) is a glucocorticoid with high topical and low systemic activity. In children aged 12 months-8 years, BIS improves asthma symptoms and lung function and decreases the need for breakthrough bronchodilators. Long-term follow-up studies in children concluded that BIS is well tolerated, with little or no effect on growth and hypothalamic-pituitary adrenal axis function. Thus it is a valuable therapeutic alternative to systemic corticosteroid therapy in infants and young children. PMID- 11213858 TI - A review of available fibrin-specific thrombolytic agents used in acute myocardial infarction. AB - Thrombolytic agents are a first-line therapeutic option for establishing coronary artery patency in acute myocardial infarction. Three fibrin-specific thrombolytics--alteplase, reteplase, and tenecteplase--are available in the United States and have undergone preliminary patency trials and large randomized, comparative, survival studies. Patency rates differ among them, although overall mortality benefit is similar. Because of this fact and the economic impact of the drugs, competition in this market is significant. Distinguishing features of the drugs will likely influence selection. Reteplase and tenecteplase offer ease of administration with bolus dosing. Increased fibrin specificity appears to play a significant role in separating them. Tenecteplase, the most highly fibrin specific, is associated with decreased risk of noncerebral bleeding and reduced need for blood transfusions in all patients, as well as longer survival in those with late presentation acute myocardial infarction. Current trials will reveal the role of these agents in combination with glycoprotein lIb-IIIa receptor antagonists. PMID- 11213859 TI - Dosing and monitoring of low-molecular-weight heparins in special populations. AB - As a result of numerous clinical trials and meta-analyses supporting the superior efficacy and relative safety of low-molecular-weight heparins (LMWHs) compared with unfractionated heparin (UFH), LMWHs are emerging as the antithrombotic agents of choice for the prevention and treatment of deep vein thrombosis and pulmonary embolism. In addition, data indicate that enoxaparin given with low dosage aspirin is more effective than UFH in treating acute coronary syndromes. Anti-Xa activity can be used as a biologic marker of LMWH activity. Because of the more predictable anticoagulant response to subcutaneous administration of LMWHs compared with UFH, routine monitoring of anti-Xa activity in clinically stable adults with uncomplicated disease is not recommended. Because the optimal dosage of LMWHs has not been established for patients with renal insufficiency or extremes of body weight, during pregnancy, or for children, anti-Xa activity monitoring may be warranted in these subsets. PMID- 11213860 TI - Implications of cytochrome P450 2C9 polymorphism on warfarin metabolism and dosing. AB - Warfarin is an anticoagulant available as a racemic mixture. The R- and S-isomers differ with respect to relative plasma concentrations, clearance, potency, sites of metabolism, and cytochrome P450 (CYP) isoenzymes responsible for metabolism. S Warfarin, the more potent isomer, is metabolized primarily by CYP2C9. Genetic polymorphisms resulting from single amino acid substitutions reduce the metabolic capability of 2C9. A reduction in warfarin metabolism due to genetic polymorphism may explain the increased warfarin response and bleeding episodes in some patients. Clinical studies showed an increased plasma level of S-warfarin, decreased clearance of S-warfarin, increased frequency of bleeding, and prolongation of hospitalization in patients with variant CYP2C9 alleles. Adverse outcomes associated with warfarin possibly could be avoided by identifying patients with variant alleles before therapy and starting therapy at low dosages. PMID- 11213861 TI - Results of a community pharmacy-based breast cancer risk-assessment and education program. AB - We tested the hypothesis that an education program addressing breast cancer screening schedules and modalities coupled with a breast cancer risk assessment provided by community pharmacists can increase women's confidence in performing screening practices endorsed by the American Cancer Society (ACS). This randomized, paired, pre-post study was conducted in six community pharmacies and two health-screening fairs; subjects were 140 women over 18 years of age. The pharmacist-administered program used the Breast Cancer Risk-Assessment Tool (Gail model) software provided by the National Cancer Institute of the National Institutes of Health. In addition, pharmacists provided education and training on breast self-examination (BSE), clinical breast examination (CBE), and mammography. Adherence to ACS guidelines for monthly BSE increased from 31% to 56% (p<0.001) for all women 6 months after the program. Performance of monthly BSE by women considered at high risk for developing breast cancer increased from 20% to 60% (p<0.005). The mean number of BSEs performed over 6 months increased from 2.69 to 4.09 (p<0.001). Women's confidence performing correct BSE improved from 6.41 to 7.04 (p<0.001) on a scale of 0-10. Adherence to ACS guidelines for CBE and mammography did not reveal statistically significant improvements except for better adherence to CBE in women aged 40-49 years (81% to 97%, p<0.025). The strength of the pharmacists' intervention may not appear as manipulation of high risk patients' behavior but as improvement of self-directed behaviors, such as BSE, across all age groups. PMID- 11213862 TI - Successful management of prolonged gamma-hydroxybutyrate and alcohol withdrawal. AB - A 27-year-old man was admitted with tremulousness, diaphoresis, tachypnea (28 breaths/min), full-body rigidity, irritability, paranoia, and auditory and visual hallucinations 2 days after stopping long-term gamma-hydroxybutyrate (GHB) and 8 hours after stopping alcohol intake. He received intravenous fluids and tapering dosages of lorazepam to control agitation and rigidity, and recovered with no significant sequelae after 8 days. Abrupt cessation of GHB after high-dosage abuse can precipitate a clinically significant withdrawal syndrome. Lorazepam should be considered for treatment of GHB withdrawal. Concomitant alcohol abuse may mask early GHB withdrawal symptoms and exacerbate withdrawal. PMID- 11213863 TI - Photosensitivity associated with fluorouracil, prochlorperazine, and topical tretinoin. AB - A woman newly diagnosed with colon cancer began chemotherapy with fluorouracil and leucovorin. Chemotherapy was given daily for 5 days with prochlorperazine premedication and was well tolerated. The patient continued her previous drug regimen during and after chemotherapy, which consisted of hormone replacement therapy, chloroquine, insulin, multivitamin, and tretinoin topical cream. Several days after the end of the first cycle of chemotherapy she experienced a dramatic photosensitivity reaction. Tretinoin application was discontinued, and she recovered. All other drugs remained unchanged. The patient was treated with five additional cycles of chemotherapy. She did not experience the reaction with any potentially photosensitizing agents again; only when the specific sequence and drug combination was administered in the first cycle. PMID- 11213864 TI - Aspirin therapy in diabetes is underutilized. PMID- 11213865 TI - Aspirin use among adults with diabetes: estimates from the Third National Health and Nutrition Examination Survey. AB - OBJECTIVE: Since 1997, the American Diabetes Association has recommended that aspirin therapy be considered for adults with diabetes who have cardiovascular disease (CVD) or CVD risk factors. We examined the prevalence of regular aspirin use among adults in the U.S. with diagnosed diabetes. RESEARCH DESIGN AND METHODS: The Third National Health and Nutrition Examination Survey (1988-1994) used a probability sample of the U.S. population and included an interview, physical examination, and laboratory studies. Among the survey participants were 1,503 adults (age > or =21 years) with self-reported diabetes. We defined regular aspirin use as reported having taken aspirin > or = 15 times in the previous month. CVD conditions were self-reported heart attack and stroke and symptoms of angina and claudication. CVD risk factors included smoking, hypertension, obesity, albuminuria, lipid abnormalities, and family history of heart attack. RESULTS: An estimated 27% of adults with diabetes had CVD, and an additional 71% had one or more CVD risk factors. Aspirin was used regularly by 37% of those with CVD and by 13% of those with risk factors only Adjusted odds of regular aspirin use were significantly greater for individuals with CVD than for those with one CVD risk factor (odds ratio [OR] = 4.3); for non-Hispanic whites than for blacks, Mexican-Americans, and others (OR = 2.5); and for individuals age 40-59 years than for those <40 years (OR = 33.3). CONCLUSIONS: Nearly every adult in the U.S. with diabetes has at least one risk factor for CVD and thus may be considered a potential candidate for aspirin therapy. During 1988-1994, only 20% (95% CI 16 23) took aspirin regularly Major efforts are needed to increase aspirin use. PMID- 11213866 TI - Impact of automated calls with nurse follow-up on diabetes treatment outcomes in a Department of Veterans Affairs Health Care System: a randomized controlled trial. AB - OBJECTIVE: We evaluated automated telephone disease management (ATDM) with telephone nurse follow-up as a strategy for improving diabetes treatment processes and outcomes in Department of Veterans Affairs (VA) clinics. We also compared the results with those of a prior ATDM trial conducted in a county health care system. RESEARCH DESIGN AND METHODS: A total of 272 VA patients with diabetes using hypoglycemic medications were randomized. During the 1-year study period, intervention patients received biweekly ATDM health assessment and self care education calls, and a nurse educator followed up with patients based on their ATDM assessment reports. Telephone surveys were used to measure patients' self-care, symptoms, and satisfaction with care. Outpatient service use was evaluated using electronic databases and self-reports, and glycemic control was measured by HbA1c and serum glucose testing. RESULTS: At 12 months, intervention patients reported more frequent glucose self-monitoring and foot inspections than patients receiving usual care and were more likely to be seen in podiatry and diabetes specialty clinics. Intervention patients also were more likely than control patients to have had a cholesterol test. Among patients with baseline HbA1c levels > or =8%, mean end-point values were lower among intervention patients than control patients (8.7 vs. 9.2%, respectively; P = 0.04). Among intervention and control patients with baseline values > or =9%, mean end-point values were 9.1 and 10.2%, respectively (P = 0.04). At follow-up, intervention patients reported fewer symptoms of poor glycemic control than control patients and greater satisfaction with their health care. CONCLUSIONS: This intervention improved the quality of VA diabetes care. Intervention effects for most end points replicated findings from the prior county clinic trial, although intervention-control differences in the current study were smaller because of the relatively good self-care and health status among the current study's enrollees. PMID- 11213867 TI - The potentially poor response to outpatient diabetes care in urban African Americans. AB - OBJECTIVE: HbA1c levels can be reduced in populations of diabetic patients, but some individuals may exhibit little improvement. To search for reasons underlying differences in HbA1c outcome, we analyzed patients managed in an outpatient diabetes clinic. RESEARCH DESIGN AND METHODS: African-Americans with type 2 diabetes were categorized as responders, intermediate responders or poor responders according to their HbA1c level after 1 year of care. Logistical regression was used to determine baseline characteristics that distinguished poor responders from responders. Therapeutic strategies were examined for each of the response categories. RESULTS: The 447 patients had a mean age and disease duration of 58 and 5 years, respectively, and BMI of 32 kg/m2. Overall, the mean HbA1c level fell from 9.6 to 8.1% after 12 months. Mean HbA1c levels improved from 8.8 to 6.2% in responders, and from 9.5 to 7.9% in intermediate responders. In poor responders, the average HbA1c level was 10.8% on presentation and 10.9% at 1 year. The odds of being a poor responder were significantly increased with longer disease duration, higher initial HbA1c level, and greater BMI. Although doses of oral agents and insulin were significantly higher among poor responders at most visits, the acceleration of insulin therapy did not occur until late in the follow-up period. CONCLUSIONS: Clinical diabetes programs need to devise methods to identify patients who are at risk for persistent hyperglycemia. Whereas patient characteristics explain some heterogeneity of HbA1c outcome (and may aid in earlier identification of patients who potentially may not respond to conventional treatment), insufficient intensification of therapy may also be a component underlying the failure to achieve glycemic goals. PMID- 11213868 TI - A foot care program for diabetic unilateral lower-limb amputees. AB - OBJECTIVE: To assess the efficacy of a specialist foot care program designed to prevent a second amputation and to assess peripheral vascular disease (PVD) and peripheral neuropathy in diabetic unilateral lower-limb amputees. RESEARCH DESIGN AND METHODS: Investigations were carried out in 143 diabetic lower-limb unilateral amputees referred to a subregional rehabilitation center for prosthetic care from a catchment area of approximately 3 million people. Peripheral vascular and nerve assessment, education, and podiatry were provided for each patient. RESULTS: For the patients referred to the foot care program, there were no baseline differences between the patients who proceeded to a bilateral amputation (n = 22) and those who remained as unilateral amputees (n = 121) in their level of foot care knowledge and mean neuropathy scores. Mean ankle brachial pressure index was significantly lower for the bilateral amputees (0.75 +/- 0.04) compared with the unilateral amputees (0.90 +/- 0.03, mean +/- SEM, P < 0.05), but there was no difference in the level of oxygen in the skin. However, the level of carbon dioxide was significantly lower in patients with bilateral amputation (24.21 +/- 2.16 vs. 31.20 +/- 0.85 mmHg, P < 0.03). Overall, the establishment of a specialist foot care program made no impact on contralateral limb amputation (22 of 143, 15.4%) compared with matched patients without the program (21 of 148, 14%) over a 2-year outcome period for each patient. CONCLUSIONS: PVD is more closely associated with diabetic bilateral amputation than neuropathy or level of foot care knowledge. Preventative foot care programs for diabetic unilateral amputees should therefore place greater emphasis on peripheral vascular assessment to identify patients at risk and on the development of timely intervention strategies. PMID- 11213869 TI - Teaching subjects with type 2 diabetes how to incorporate sugar choices into their daily meal plan promotes dietary compliance and does not deteriorate metabolic profile. AB - OBJECTIVE: To determine whether teaching free-living subjects with type 2 diabetes how to incorporate added sugars or sweets into their daily meal plan results in a greater consumption of calories (fat or sugar) and deteriorates their glycemic or lipid profiles but improves their perceived quality of life. RESEARCH DESIGN AND METHODS: In an 8-month randomized controlled trial, 48 free living subjects with type 2 diabetes were taught either a conventional (C) meal plan (no concentrated sweets) or one permitting as much as 10% of total energy as added sugars or sweets (S). Mean individual nutrient intake was determined using the average of six 24-h telephone recalls per 4 months. Metabolic control and quality of life were evaluated every 2 months. Quality of life was assessed using the Medical Outcome Survey and the Diabetes Quality of Life questionnaire. RESULTS: The S group did not consume more calories (fat or sugar) and in fact ate significantly less carbohydrate (-15 vs. 10 g) and less starch (-7 vs. 8 g) and had a tendency to eat fewer calories (-77 vs. 81 kcal) than the C group. Weight remained stable, and there was no evidence that consuming more sugar worsened metabolic profile or improved their perceived quality of life. CONCLUSIONS: Giving individuals with type 2 diabetes the freedom to include sugar in their daily meal plan had no negative impact on dietary habits or metabolic control. Health professionals can be reassured and encouraged to teach the new "sugar guidelines," because doing so may result in a more conscientious carbohydrate consumption. PMID- 11213870 TI - Beneficial effects of a soy-based dietary supplement on lipid levels and cardiovascular risk markers in type 2 diabetic subjects. AB - OBJECTIVE: Consumption of soy protein has recently been shown to improve the blood lipid levels in nondiabetic subjects. The purpose of this study was to evaluate if a dietary supplement of soy protein, isoflavones, and cotyledon fiber (Abalon) affects cardiovascular risk markers, blood glucose, and insulin levels in type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: Twenty type 2 diabetic subjects participated in a crossover trial. They were randomized to double-blind supplementation for 6 weeks with Abalon (soy protein [50 g/day] with high levels of isoflavones [minimum 165 mg/day] and cotyledon fiber [20 g/day]) or placebo (casein [50 g/day] and cellulose [20 g/day]), separated by a 3-week wash-out period. RESULTS: The results are expressed as means +/- SD. The percentage mean treatment difference between Abalon and placebo demonstrated significantly lower mean values after Abalon for LDL cholesterol (10 +/- 15%, P < 0.05), LDL/UHDL ratio (12 +/- 18%, P < 0.05), apolipoprotein (apo) B100 (30 +/- 38%, P < 0.01), triglycerides (22 +/- 10%, P < 0.05), and homocysteine (14 +/- 21%, P < 0.01), whereas the total cholesterol value tended to be less significant but still lower (8 +/- 15%, P < 0.08). No change occurred in HDL cholesterol, apo B100/apo A1 ratio, plasminogen activator inhibitor 1, factor VIIc, von Willebrand factor, fibrinogen, lipoprotein(a), glucose, HbA1c, or 24-h blood pressure. CONCLUSIONS: These results indicate beneficial effects of dietary supplementation with Abalon on cardiovascular risk markers in type 2 diabetic subjects. This improvement is seen even in individuals with near-normal lipid values. PMID- 11213871 TI - Comparison of single-mother and two-parent families on metabolic control of children with diabetes. AB - OBJECTIVE: To understand the impact of family structure on the metabolic control of children with diabetes, we posed two research questions: 1) what are the differences in sociodemographic, family, and community factors between single mother and two-parent families of diabetic children? and 2) to what extent do these psychosocial factors predict metabolic control among diabetic children from single-mother and two-parent families? RESEARCH DESIGN AND METHODS: This cross sectional study included 155 diabetic children and their mothers or other female caregivers. The children were recruited if they had been diagnosed with diabetes for at least 1 year, had no other comorbid chronic illnesses, and were younger than 18 years of age. Interviews and self-report questionnaires were used to assess individual, family, and community variables. RESULTS: The findings indicate that diabetic children from single-mother families have poorer metabolic control than do children from two-parent families. Regression models of children's metabolic control from single-mother families indicate that age and missed clinic appointments predicted HbA1c levels; however, among two-parent families, children's ethnicity and adherence to their medication regimen significantly predicted metabolic control. CONCLUSIONS: This study suggests that children from single-mother families are at risk of poorer metabolic control and that these families have more challenges to face when raising a child with a chronic illness. Implications point to a need for developing strategies sensitive to the challenges of single mothers. PMID- 11213872 TI - Factors influencing glycemic control in young people with type 1 diabetes in Scotland: a population-based study (DIABAUD2). AB - OBJECTIVE: To evaluate differences in HbA1c concentrations between centers and to assess the factors associated with glycemic control in young people with type 1 diabetes in Scotland. RESEARCH DESIGN AND METHODS: Data on 1,755 patients (94% of those registered) were collected from 18 centers providing care to children <15 years of age. At every clinic visit, a duplicate HbA1c sample was measured in a reference laboratory, and clinical information was collected prospectively. RESULTS: Average HbA1c concentration was 9.1% (range 5.0-15.0). The following significant associations with HbA1c level were identified: age, insulin regimen, BMI, season, social circumstances, and family history. HbA1c concentrations were significantly worse in older children (age 10-15 years 9.5% vs. other ages 8.8%, P < 0.001), those using two injections per day (2/day 9.1% vs. 3/day 8.8%, P < 0.01), children without both parents at home (9.4 vs. 9.0%, P < 0.001), a sibling with diabetes (9.7% vs. no family history 9.1%, P < 0.001). HbA1c concentration ranged from 8.1 to 10.2% between centers, after adjustment for factors associated with poor HbA1c (P < 0.001). CONCLUSIONS: The overall glycemic control of diabetic young people in Scotland is equivalent to a Diabetes Control and Complications Trial HbA1c concentration of 8.7%, placing the majority at a high risk of the complications of diabetes in adulthood. Although factors were significantly associated with poor HbA1c adjustment for these did not explain the differences between centers. We suggest that factors not analyzed in DIABAUD2 (e.g., deployment of resources, organization of the clinical structure, strategies of care, and clinic philosophy) are the determinants of HbA1c. We speculate that the style of utilization of optimum resources is the key to achieving good glycemic control. PMID- 11213873 TI - Limited value of the homeostasis model assessment to predict insulin resistance in older men with impaired glucose tolerance. AB - OBJECTIVE: Insulin resistance (IR) in older individuals is associated with risk factors for coronary artery disease. The glucose clamp measures IR directly, but the homeostasis model assessment (HOMA) of IR, referred to here as HOMA-IR, is based on fasting glucose and insulin and is less invasive and labor intensive. This method requires validation in the elderly. RESEARCH DESIGN AND METHODS: We assessed the validity of HOMA-IR as an index of IR by comparing it to glucose infusion rates (GIRs) measured by a glucose clamp (600 pmol x m(-2) x min(-1)) in 45 obese men (61 +/- 8 years of age, mean +/- SD) with normal glucose tolerance (NGT) (n = 21) or impaired glucose tolerance (IGT) (n = 24). We also evaluated relationships between body composition, exercise capacity, and IR. RESULTS: Subjects with NGT had lower BMI (28 +/- 3 vs. 31 +/- 3 kg/m2), waist circumference (97 +/- 9 vs. 105 +/- 9 cm), waist-to-hip ratio (WHR) (0.93 +/- 0.06 vs. 0.97 +/- 0.05), and percent body fat (25 +/- 6 vs. 30 +/- 6) than subjects with IGT. Subjects with NGT also had lower areas above basal during the 2-h oral glucose tolerance test for glucose (274 +/- 95 vs. 419 +/- 124 mmol x min/l) and insulin (38,142 +/- 18,206 vs. 58,383 +/- 34,408 pmol x min/l) and lower HOMA-IR values (2.2 +/- 0.8 vs. 4.2 +/- 2.6) than subjects with IGT. GIR (micromol x kg(-1) FFM x min(-1)) was higher in subjects with NGT than in subjects with IGT (53 +/- 11 vs. 43 +/- 14). HOMA-IR correlated with GIR in subjects with NGT (r = -0.59), but not in subjects with IGT (r = -0.13). GIR correlated with VO2max in subjects with NGT (r = 0.58) and IGT (r = 0.42), but with WHR only in subjects with NGT (r = -0.53). HOMA-IR correlated with VO2max (r = -0.57) and waist circumference (r = 0.54) in subjects with NGT, but with percent body fat in subjects with IGT (r = 0.54). CONCLUSIONS: These findings indicate that HOMA-IR should not be used as an index of IR in older individuals who may be at risk for IGT, and suggest that lifestyle changes that increase VO2max and decrease body fat may reduce IR in older people. PMID- 11213874 TI - Simple screening tests for peripheral neuropathy in the diabetes clinic. AB - OBJECTIVE: The utility of rapid and reliable sensory tests appropriate for the diagnosis of neuropathy in the diabetes clinic, rather than as prognostic tools for the prediction of foot complications, has been unclear because of limitations inherent in previous studies. Although clinical practice guidelines recommend annual screening for neuropathy, they are unable to support specific recommendations for screening maneuvers because of a lack of evidence for the validity of screening tests in the medical literature. The objective of this study was to assess the operating characteristics of four simple sensory screening maneuvers as compared with standardized electrophysiological tests in the diagnosis of distal symmetrical polyneuropathy. RESEARCH DESIGN AND METHODS: We assessed four simple tests (the 10-g Semmes-Weinstein monofilament examination [SWME], superficial pain sensation, vibration testing by the on-off method, and vibration testing by the timed method) in 478 subjects with independent blinded evaluations compared against the criterion standard of nerve conduction studies. We present receiver-operating characteristic (ROC) curves, positive and negative likelihood ratios, and sensitivity and specificity values for each test. RESULTS: The four simple screening maneuvers reveal similar operating characteristics. Cutoff points by ROC curve analyses reveal that a positive or abnormal test is represented by five incorrect responses of eight stimuli applied. A negative or normal test is represented by one or fewer incorrect responses of eight stimuli applied. By these criteria, the point estimates of the positive likelihood ratios for vibration testing by the on-off method, vibration testing by the timed method, the SWME, and superficial pain sensation test are 26.6, 18.5, 10.2, and 9.2, respectively. The point estimates of the negative likelihood ratios are 0.33, 0.51, 0.34, and 0.50, respectively The screening tests showed comparable sensitivity and specificity results. The 10-g SWME, superficial pain test, and vibration testing by the on-off method are rapid, each requiring approximately 60 s to administer. The timed vibration test takes longer, and the interpretation is more complicated. The combination of two simple tests (e.g., the 10-g SWME and vibration testing by the on-off method) does not add value to each individual screening test. CONCLUSIONS: Annual screening for diabetic neuropathy should be conducted using superficial pain sensation testing, SWME, or vibration testing by the on-off method. The reported operating characteristics for each sensory modality can be applied to positive findings on the physical examination of individual patients to predict the likelihood of neuropathy. PMID- 11213875 TI - Productivity losses associated with diabetes in the US. AB - OBJECTIVE: The objective of this study was to estimate the cost of productivity losses in the U.S. attributable to diabetes, with regard to specific demographic and disease-related characteristics in the U.S.. RESEARCH DESIGN AND METHODS: We used the 1989 National Health Interview Survey, a random survey of individuals in the U.S. that included a diabetes supplement. Data on individuals were obtained for labor force participation, hours of work, demographic and occupational characteristics, self-reported health status, and several variables that indicated the presence, duration, and severity (complications) of diabetes. Using multivariate regression analyses, we estimated the association of independent variables (e.g., demographics, health, and diabetes status) with labor force participation, hours of work lost, and the economic value of lost work attributable to diabetes and its complications and duration. RESULTS: In general, the presence of diabetes and complications were found to be related to workforce participation variables. The magnitude of the lost-productivity costs depended on personal characteristics and on the presence and status of diabetes. In general, the loss of yearly earnings amounted to about a one-third reduction in earnings and ranged from $3,700 to $8,700 per annum. CONCLUSIONS: Diabetes has a considerable net effect on earnings, and the complications and duration of diabetes have compound effects. Our findings have implications for the cost effectiveness of diabetes control; the presence of complicating factors is the single most important predictive factor in lost productivity costs attributable to diabetes, and thus the avoidance or retardation of complications will have an impact on indirect health-related costs. PMID- 11213876 TI - The Oregon Health Plan: predictors of office-based diabetic quality of care. AB - OBJECTIVE: In 1994, the Oregon Health Plan (OHP) expanded basic Medicaid insurance to residents under the federal poverty limit, adopted a prioritized limited benefits package, and converted to managed care. The quality of care in predominantly Medicaid populations with diabetes has not been previously described. In OHP enrollees, we examined predictors of diabetes care based on American Diabetes Association guidelines and described OHP diabetes care compared with national benchmarks. RESEARCH DESIGN AND METHODS: Chart abstraction and Medicaid data for 1995-1996 yielded 996 nonpregnant diabetic patients who were 18 64 years of age. Using HbA1c, lipid panel, and urine protein/microalbumin documentation ordered during the study year, we constructed a standard care (SC) index: SC for all three tests, mixed care (MC) for one to two tests, or no tests documented (NTD). RESULTS: Our sample was predominantly white, 48 +/- 11 years of age, 63% women, with 8 +/- 5 provider visits. Providers ordered HbA1c (70%), urine microalbumin/protein (57%), and lipid panel (41%) tests. Patients distributed into SC (22%), MC (62%), or NTD (16%). Thirteen variables predicted SC. Patients had a higher likelihood of SC if they were 18-24 years of age, had more clinic visits, were on insulin daily, were in several comorbid groups, were enrolled in salaried or capitated health plans, or lived in counties with more hospital beds. Four studies were used as comparable national benchmarks. CONCLUSIONS: Care provided to OHP patients with diabetes compares favorably with national benchmarks. Yet, most OHP patients with diabetes are still not achieving optimal care. Examining predictors of SC may play an important role in further policy development. PMID- 11213877 TI - Barriers to providing diabetes care in community health centers. AB - OBJECTIVE: We aimed to identify barriers to improving care for individuals with diabetes in community health centers. These findings are important because many such patients, as in most other practice settings, receive care that does not meet evidence-based standards. RESEARCH DESIGN AND METHODS: In 42 Midwestern health centers, we surveyed 389 health providers and administrators about the barriers they faced delivering diabetes care. We report on home blood glucose monitoring, HbA1c tests, dilated eye examinations, foot examinations, diet, and exercise, all of which are a subset of the larger clinical practice recommendations of the American Diabetes Association (ADA). RESULTS: Among the 279 (72%) respondents, providers perceived that patients were significantly less likely than providers to believe that key processes of care were important (overall mean on 30-point scale: providers 26.8, patients 18.2, P = 0.0001). Providers were more confident in their ability to instruct patients on diet and exercise than on their ability to help them make changes in these areas. Ratings of the importance of access to care and finances as barriers varied widely; however, >25% of the providers and administrators agreed that significant barriers included affordability of home blood glucose monitoring, HbA1c testing, dilated eye examination, and special diets; nonproximity of ophthalmologist; forgetting to order eye examinations and to examine patients' feet; time required to teach home blood glucose monitoring; and language or cultural barriers. CONCLUSIONS: Providers in health centers indicate a need to enhance behavioral change in diabetic patients. In addition, better health care delivery systems and reforms that improve the affordability, accessibility, and efficiency of care are also likely to help health centers meet ADA standards of care. PMID- 11213878 TI - The metabolic syndrome in the West Bank population: an urban-rural comparison. AB - OBJECTIVE: To compare the prevalence of components of the metabolic syndrome, including hypertension, abnormal glucose metabolism, dyslipidemia, central obesity, and overall obesity, between a rural and an urban Palestinian West Bank community. RESEARCH DESIGN AND METHODS: A total of 500 rural and 492 urban men and women aged 30-65 years participated in a community-based cross-sectional survey Diabetes and impaired glucose tolerance were diagnosed using the oral glucose tolerance test. BMI, waist-to-hip ratio, and blood pressure were measured, and blood samples were taken from each subject. Sociodemographic characteristics were investigated using a questionnaire. RESULTS: Hypertriglyceridemia, low HDL cholesterol, overall obesity, and smoking were significantly more prevalent in the urban population, whereas central obesity was more prevalent in the rural population. Prevalence of hypertension was not significantly different between the rural and urban populations (25.4 and 21.5%, respectively; P = 0.15). The age-adjusted prevalences of diabetes were high: 11.3% (8.5-14.1 95% CI) and 13.9% (10.8-17.0) in the rural and urban populations, respectively, but not significantly different. In each community, the age adjusted prevalence of the metabolic syndrome as defined by the World Health Organization was 17%. CONCLUSIONS: Although no significant differences were found in the prevalences of hypertension and diabetes between the two populations, other components of the metabolic syndrome, namely elevated triglycerides, low HDL cholesterol, and overall obesity, were more prevalent in the urban population. Given the rapid urbanization of the Palestinian population, the implications for a rise in noncommunicable diseases should be a major public health concern. PMID- 11213879 TI - African-American women have higher initial HbA1c levels in diabetic pregnancy. AB - OBJECTIVE: African-American women with diabetes are at greater risk for poor glycemic control outside of pregnancy. We evaluated the effect of race on glycemic control in a racially mixed population of women with diabetes entering prenatal care. RESEARCH DESIGN AND METHODS: HbA1c levels along with demographic data were collected at the first prenatal visit from a group of 234 women with preexisting diabetes. We applied logistic multivariate analysis to identify factors associated with HbA1c levels above the median for the group. RESULTS: The median HbA1c level for the group was 8%. HbA1c levels were 8.7 +/- 2.0% in African-Americans and 7.7 +/- 1.5% in Caucasians (P < 0.001). African-American racial designation was significantly and independently associated with high HbA1c when controlled for maternal age, parity, White classification, diabetes type, education, marital status, obesity, insurance type, and first trimester entry into care. The effect of race was confined to the nonobese patients, for whom the adjusted odds ratio for African-American race as a predictor of high HbA1c was 8.15 with a 95% CI of 2.41-27.58 (P = 0.001). CONCLUSIONS: We found a clear racial disparity in glycemic control among women entering prenatal care with preexisting diabetes. This study demonstrates that there generally is need for better glycemic control among reproductive-age women with diabetes, but especially among those who are African-American. PMID- 11213880 TI - Markers of insulin resistance are strong risk factors for retinopathy incidence in type 1 diabetes. AB - OBJECTIVE: To determine the incidence of retinopathy and the relative importance of its risk factors in type 1 diabetes. RESEARCH DESIGN AND METHODS: This is a 7.3-year follow-up of 764 of 1,215 (63%) people with type 1 diabetes across Europe, aged 15-60 years at baseline with no retinopathy (the EURODIAB Prospective Complications Study). Retinal photographs were taken at baseline and follow-up and risk factors were assessed to a standard protocol. RESULTS: Retinopathy incidence was 56% (429/764, 95% CI 52-59%). Key risk factors included diabetes duration and glycemic control. We found no evidence of a threshold effect for HbA1c on retinopathy incidence. Univariate associations were observed between incidence and albumin excretion rate, cholesterol, triglyceride, fibrinogen, von Willebrand factor, gamma-glutamyltransferase, waist-to-hip ratio, and insulin dose. No associations were observed for blood pressure, cardiovascular disease, or smoking. Independent risk factors, as assessed by standardized regression effects, were HbA1C (1.93, P = 0.0001), duration (1.32, P = 0.008), waist-to-hip ratio (1.32, P = 0.01), and fasting triglyceride (1.24, P = 0.04). CONCLUSIONS: Retinopathy incidence in type 1 diabetes remains high. Key risk factors include diabetes duration and glycemic control, with no evidence of a threshold for the latter. Other independent risk factors, such as waist-to-hip ratio and triglyceride levels, both markers of insulin resistance, were strongly related to incidence. PMID- 11213881 TI - Graftskin, a human skin equivalent, is effective in the management of noninfected neuropathic diabetic foot ulcers: a prospective randomized multicenter clinical trial. AB - OBJECTIVE: We assessed in a randomized prospective trial the effectiveness of Graftskin, a living skin equivalent, in treating noninfected nonischemic chronic plantar diabetic foot ulcers. RESEARCH DESIGN AND METHODS: In 24 centers in the U.S., 208 patients were randomly assigned to ulcer treatment either with Graftskin (112 patients) or saline-moistened gauze (96 patients, control group). Standard state-of-the-art adjunctive therapy, which included extensive surgical debridement and adequate foot off-loading, was provided in both groups. Graftskin was applied at the beginning of the study and weekly thereafter for a maximum of 4 weeks (maximum of five applications) or earlier if complete healing occurred. The major outcome of complete wound healing was assessed by intention to treat at the 12-week follow-up visit. RESULTS: At the 12-week follow-up visit, 63 (56%) Graftskin-treated patients achieved complete wound healing compared with 36 (38%) in the control group (P = 0.0042). The Kaplan-Meier median time to complete closure was 65 days for Graftskin, significantly lower than the 90 days observed in the control group (P = 0.0026). The odds ratio for complete healing for a Graftskin-treated ulcer compared with a control-treated ulcer was 2.14 (95% CI 1.23-3.74). The rate of adverse reactions was similar between the two groups with the exception of osteomyelitis and lower-limb amputations, both of which were less frequent in the Graftskin group. CONCLUSIONS: Application of Graftskin for a maximum of 4 weeks results in a higher healing rate when compared with state-of the-art currently available treatment and is not associated with any significant side effects. Graftskin may be a very useful adjunct for the management of diabetic foot ulcers that are resistant to the currently available standard of care. PMID- 11213882 TI - Comparison of the soluble basal insulin analog insulin detemir with NPH insulin: a randomized open crossover trial in type 1 diabetic subjects on basal-bolus therapy. AB - OBJECTIVE: Insulin detemir (NN304) is a soluble basal insulin analog developed to cover basal insulin requirements. This trial aimed to compare the blood glucose lowering effect of insulin detemir with that of NPH insulin (NPH) and to evaluate the two treatments with regard to intrasubject variation of fasting blood glucose, incidence of hypoglycemia, dose requirements, and safety. RESEARCH DESIGN AND METHODS: This multicenter open randomized crossover trial in 59 type 1 diabetic subjects comprised a 2-week run-in period on a basal-bolus regimen with NPH insulin once daily, followed by two 6-week periods of optimized basal-bolus therapy with either once-daily insulin detemir or NPH insulin. RESULTS: The area under the curve, in the time interval 23:00-8:00, derived from 24-h serum glucose profiles, was not statistically significantly different for the two treatment periods (insulin detemir:NPH ratio 89.2:83.5, P = 0.59). The intrasubject variation in fasting blood glucose during the last 4 days of treatment was lower for insulin detemir compared with NPH (P < 0.001). Mean dose requirements of insulin detemir were 2.35 times higher (95% CI 2.22-2.48) compared with NPH. During the last week of treatment, fewer subjects experienced hypoglycemic episodes on insulin detemir (60%) compared with NPH treatment (77%) (P = 0.049). CONCLUSIONS: Insulin detemir was as effective as NPH in maintaining glycemic control when administered at a higher molar dose. The results indicate that insulin detemir may provide more predictable fasting blood glucose with lower intrasubject variation and reduced risk of hypoglycemia compared with NPH. PMID- 11213883 TI - Macrophage activation in type 1 diabetic patients with catheter obstruction during peritoneal insulin delivery with an implantable pump. AB - OBJECTIVE: The purpose of this study was to evaluate the activation of macrophages in type 1 diabetic patients during peritoneal insulin delivery with an implantable pump against two types of insulin: that which was collected from the pump reservoir and that which came straight fromn the bottle (i.e., vial insltlin). Macrophage activation was studied in patients with and without cathcter obstruction and compared with activation in healthy subjects. RESEARCH DESIGN AND METHODS: Human insulin (21 PH, 400 U/ml; Hoescht) was collected from the pump reservoir (Minimed) of diabetic patients with (n = 3) or without (n = 7) catheter obstruction, as assessed by histological examination of the catheter tip. Monocytes were obtained from venous blood samples from both kinds of diabetic patients and from healthy subjects (n = 5) and were differentiated into monocyte-derived macrophages in culture. Their chemotaxis and tumor necrosis factor-alpha (TNF-alpha) release were studied with respect to both types of insulin, as previously stated. Formyl-methionyl-leucyl-phenylalanine (fMLP) and lipopolysaccharide (LPS) were used as controls. RESULTS: Neither insulin recovered from the pump reservoir nor vial insulin proved chemotactic to macrophages from either healthy subjects or those diabetic patients with and without catheter obstruction. The migration toward fMLP of macrophages from patients presenting a catheter obstruction was significantly higher than that observed with macrophages from either diabetic patients without obstruction or healthy subjects, the chemotactic index (mean +/- SD) was 3.81 +/- 0.36 vs. 2.30 +/- 0.89 and 2.60 +/- 0.80, respectively (P < 0.05). LPS significantly stimulated the TNF-alpha secretion of macrophages from diabetic subjects with a catheter obstruction, whereas both native and reservoir-recovered insulin had no effect on this release (144.83 +/- 67.25 vs. 5.15 +/- 2.93 and 5.27 +/- 2.43 pg/ml, P < 0.001). CONCLUSIONS: The human insulin used in implantable pumps, regardless of how long it had remained in the pump reservoir, did not induce macrophage activation in diabetic patients treated through intraperitoneal insulin delivery. In some of these diabetic patients, catheter obstruction could be explained by their high capacity of macrophage chemotaxis. PMID- 11213884 TI - Once- and twice-daily dosing with rosiglitazone improves glycemic control in patients with type 2 diabetes. AB - OBJECTIVE: To determine the efficacy of rosiglitazone compared with placebo in reducing hyperglycemia. RESEARCH DESIGN AND METHODS: After a 4-week placebo run in period, 959 patients were randomized to placebo or rosiglitazone (total daily dose 4 or 8 mg) for 26 weeks. The primary measure of efficacy was change in the HbA1c concentration. RESULTS: Rosiglitazone produced dosage-dependent reductions in HbA1c of 0.8, 0.9, 1.1, and 1.5% in the 4 mg o.d., 2 mg b.i.d., 8 mg o.d., and 4 mg b.i.d. groups, respectively, compared with placebo. Clinically significant decreases from baseline in HbA1c were observed in drug-naive patients at all rosiglitazone doses and in patients previously treated with oral monotherapy at rosiglitazone 8 mg o.d. and 4 mg b.i.d. Clinically significant decreases from baseline in HbA1c were also observed with rosiglitazone 4 mg b.i.d. in patients previously treated with combination oral therapy. Approximately 33% of drug-naive patients treated with rosiglitazone achieved HbA1c < or =7% at study end. The proportions of patients with at least one adverse event were comparable among the rosiglitazone and placebo groups. There was no evidence of hepatotoxicity in any treatment group. There were statistically significant increases in weight and serum lipids in all rosiglitazone treatment groups compared with placebo. For LDL and HDL cholesterol, the observed increase appeared to be dose related. CONCLUSIONS: Rosiglitazone at total daily doses of 4 and 8 mg significantly improved glycemic control in patients with type 2 diabetes and was well tolerated. PMID- 11213885 TI - Relationship between plasma sialic acid concentration and microvascular and macrovascular complications in type 1 diabetes: the EURODIAB Complications Study. AB - OBJECTIVE: To test the hypothesis that an increased plasma concentration of sialic acid, a marker of the acute-phase response, is related to the presence of diabetic micro- and macrovascular complications in type 1 diabetes. RESEARCH DESIGN AND METHODS: We investigated the relationship between plasma sialic acid concentration and nephropathy, retinopathy, neuropathy, and coronary heart disease (CHD) in a cross-sectional survey of 1,369 people with type 1 diabetes. Subjects were participants in the EURODIAB IDDM Complications Study, which involved 31 centers in 16 European countries. RESULTS: There was a significantly increasing trend of plasma sialic acid with severity of retinopathy (P < 0.001 in men) and with degree of urinary albumin excretion (P < 0.001 men, P < 0.01 women). Plasma sialic acid correlated with increasing plasma creatinine concentration (P < 0.009 men, P < 0.0002 women), and men with neuropathy had a higher plasma sialic acid concentration than those without (P < 0.006). There was no significant correlation between plasma sialic acid and CHD in either sex. Elevated plasma sialic acid concentrations were also associated with several risk factors for diabetic vascular disease: diabetes duration, HbA1c, plasma triglyceride and cholesterol concentrations, waist-to-hip ratio, hypertension and smoking (in men), and low physical exercise (in women). In multiple logistic regression analysis, plasma sialic acid was independently related to proliferative retinopathy and urinary albumin excretion rate in men. CONCLUSIONS: We conclude that an elevated plasma sialic concentration is strongly related to the presence of microvascular complications in type 1 diabetes, especially retinopathy and nephropathy. Further study of acute-phase response markers and mediators as indicators or predictors of diabetic microvascular complications is therefore justified. PMID- 11213886 TI - Plasma levels of cellular fibronectin in diabetes. AB - OBJECTIVE: Cellular fibronectin is an endothelium-derived protein involved in subendothelial matrix assembly. Elevated plasma levels of cellular fibronectin therefore reflect loss of endothelial cell polarization or injury to blood vessels. Consequently, elevated plasma levels of circulating cellular fibronectin have been described in clinical syndromes with vascular damage, although not in diabetes or atherosclerosis. RESEARCH DESIGN AND METHODS: We determined fibronectin levels in 52 patients with type 1 diabetes, 50 patients with type 2 diabetes, 54 patients with a history of ischemic stroke, 23 patients with renal artery stenosis, and 64 healthy subjects. RESULTS: Circulating cellular fibronectin was significantly elevated in patients with diabetes (4.3 +/- 2.8 microg/ml) compared with patients with ischemic stroke (2.0 +/- 0.9 microg/ml), patients with renovascular hypertension (1.7 +/- 1.1 microg/ml), and healthy subjects (1.4 +/- 0.6 microg/ml). Patients with diabetes and at least one cardiovascular risk factor had an almost 2.5-fold increase in cellular fibronectin compared with diabetic subjects without such a risk factor. In multivariate regression analysis, higher triglycerides, current or past cigarette smoking, and higher urinary albumin excretion were independently associated with an increase in circulating cellular fibronectin in diabetes. CONCLUSIONS: These results suggest that circulating cellular fibronectin may be a marker protein for endothelial cell activation, especially in diabetes. Prospective studies are needed to explore this possibility PMID- 11213887 TI - Plasma levels of tumor necrosis factor-alpha, angiotensin II, growth hormone, and IGF-I are not elevated in insulin-resistant obese individuals with impaired glucose tolerance. AB - OBJECTIVE: To investigate the relationship between insulin resistance and plasma concentrations of free fatty acids (FFAs), leptin, and potential agonists of the insulin receptor substrate (IRS) system, including tumor necrosis factor-alpha (TNF-alpha), IGF-I, growth hormone (GH), and angiotensin II in individuals with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: Because glucose toxicity per se leads to insulin resistance, the determination of the primary metabolic alterations leading to insulin resistance is best accomplished in individuals who are at an increased risk to develop type 2 diabetes. Therefore, 48 subjects with IGT and insulin resistance (IR), characterized by hyperinsulinemic-euglycemic clamps, were compared with 52 healthy insulin sensitive (IS) control subjects with respect to the relationship between the plasma levels of TNF-alpha, IGF-I, GH, angiotensin II, FFA, leptin, and insulin resistance. RESULTS: Between the IR and the IS groups, there were no significant differences in the plasma concentrations of TNF-alpha, GH, angiotensin II, IGF-I, and leptin. However, plasma FFA levels were significantly elevated in the IR group compared with the IS group after matching for BMI. CONCLUSIONS: The plasma concentrations of FFA, but not TNF-alpha, IGF-I, GH, and angiotensin II, are elevated in patients at an early stage of insulin resistance, suggesting that FFAs, but not the other modulators of the IRS system, may be a primary metabolic abnormality leading to insulin resistance. PMID- 11213888 TI - Increased prevalence of significant coronary artery calcification in patients with diabetes. AB - OBJECTIVE: Coronary artery disease is the major cause of morbidity and mortality in patients with diabetes. Detection of coronary artery disease before the first myocardial infarction and before anginal symptoms will allow for strategies designed to reduce the cardiovascular event rate in this group of patients. Electron beam-computed tomography (EBCT) is a noninvasive technology for evaluating the extent of coronary artery atherosclerosis that relies on the detection of coronary artery calcium (CAC). We used EBCT to detect significant coronary artery atherosclerosis in diabetic patients without symptoms of heart disease. RESEARCH DESIGN AND METHODS: We used EBCT to evaluate calcium in the coronary arteries of 139 consecutive diabetic patients scanned over a 20-month period. The CAC scores in this group were compared with a randomly selected nondiabetic control group and a control group that was selected to match a number of established cardiovascular risk factors. RESULTS: Patients with diabetes had a significant increase in the prevalence of CAC scores > or =400 (25.9%) compared with the randomly selected (7.2%) and matched (14.4%) nondiabetic control groups. Scores in this range have been reported to be highly predictive for abnormal stress myocardial perfusion tomography and subsequent coronary events. CONCLUSIONS: Our results, therefore, indicate a substantial prevalence of significant coronary artery disease in an asymptomatic diabetic patient population compared with nondiabetic control subjects. They also suggest that EBCT may be a useful approach for selecting a group of diabetic subjects who would benefit most from additional evaluation for subclinical coronary artery disease. PMID- 11213889 TI - Predictive value of cardiac autonomic neuropathy in diabetic patients with or without silent myocardial ischemia. AB - OBJECTIVE: The aim of this study was to determine the predictive value of silent myocardial ischemia (SMI) and cardiac autonomic neuropathy (CAN) in asymptomatic diabetic patients. RESEARCH DESIGN AND METHODS: We recruited 120 diabetic patients with no history of myocardial infarction or angina, a normal 12-lead electrocardiogram (ECG), and two or more additional risk factors. SMI assessment was carried out by means of an ECG stress test, a thallium-201 myocardial scintigraphy with dipyridamole, and 48-h ECG monitoring. CAN was searched for by standardized tests evaluating heart rate variations. Accurate follow-up information for 3-7 years (mean 4.5) was obtained in 107 patients. RESULTS: There was evidence of SMI in 33 patients (30.7%). CAN was detected in 33 of the 75 patients (38.9%) who were tested, and a major cardiac event occurred in 11 of them. Among these 75 patients, the proportion of major cardiac events in the SMI+ patients was not significantly higher than that in the SMI- patients (6 of 25 vs. 5 of 50 patients), whereas it was significantly higher in the CAN+ patients than in the CAN- patients (8 of 33 vs. 3 of 42 patients; P = 0.04), with a relative risk of 4.16 (95% CI 1.01-17.19) and was the highest in the patients with both SMI and CAN (5 of 10 patients). After adjusting for SMI, there was a significant association between CAN and major cardiac events (P = 0.04). CONCLUSIONS: In asymptomatic diabetic patients, CAN appears to be a better predictor of major cardiac events than SMI. The risk linked to CAN appears to be independent of SMI and is the highest when CAN is associated with SMI. PMID- 11213890 TI - Contribution of nerve-axon reflex-related vasodilation to the total skin vasodilation in diabetic patients with and without neuropathy. AB - OBJECTIVE: To examine the contribution of nerve-axon reflex-related vasodilation to total acetylcholine-induced vasodilation in the skin of normal and diabetic subjects. RESEARCH DESIGN AND METHODS: The skin microcirculation was evaluated at the forearm level in 69 healthy subjects and 42 nonneuropathic diabetic patients and at the foot level in 27 healthy subjects and 101 diabetic patients (33 with neuropathy, 23 with Charcot arthropathy, 32 with peripheral vascular disease and neuropathy, and 13 without complications). Two single-point laser probes were used to measure total and neurovascular vasodilation response to the iontophoresis of 1% acetylcholine, 1% sodium nitroprusside, and deionized water. RESULTS: The neurovascular response to acetylcholine was significantly higher than the response to sodium nitroprusside and deionized water (P < 0.01). At the forearm level, the contribution of neurovascular response to the total response to acetylcholine was 35% in diabetic patients and 31% in control subjects. At the foot level, the contribution was 29% in diabetic patients without neuropathy and 36% in control subjects, while it was significantly diminished in the three neuropathic groups. A significantly lower nonspecific nerve-axon-related vasodilation was observed during the iontophoresis of sodium nitroprusside, which does not specifically stimulate the C nociceptive fibers. CONCLUSIONS: Neurovascular vasodilation accounts for approximately one-third of the total acetylcholine-induced vasodilation at both the forearm and foot levels. The presence of diabetic neuropathy results in reduction of both the total vasodilatory response to acetylcholine and the percentage contribution of neurovascular vasodilation to the total response. Acetylcholine and sodium nitroprusside cause vasodilation in the skin microcirculation through different pathways. PMID- 11213891 TI - Differential influence of LDL cholesterol and triglycerides on lipoprotein(a) concentrations in diabetic patients. AB - OBJECTIVE: To evaluate the relationship between plasma lipid profiles and lipoprotein(a) [Lp(a)] concentrations in diabetic patients, taking into account the Lp(a) phenotype. RESEARCH DESIGN AND METHODS: We included 191 consecutive diabetic outpatients (69 type 1 and 122 type 2 diabetic patients) in a cross sectional study Serum Lp(a) was determined by enzyme-linked immunosorbent assay, and Lp(a) phenotypes were assessed by SDS-PAGE followed by immunoblotting. The statistical methods included a stepwise multiple regression analysis using the Lp(a) serum concentration as the dependent variable. The lipid profile consisted of total cholesterol, HDL cholesterol, LDL cholesterol, corrected LDL cholesterol, triglycerides, and apolipoproteins AI and B. RESULTS: In the multiple regression analysis, LDL cholesterol (positively) and triglycerides (negatively) were independently related to the Lp(a) concentration, and they explained the 6.6 and 7.8% of the Lp(a) variation, respectively. After correcting LDL cholesterol, the two variables explained 3.8 and 6.4% of the Lp(a) variation, respectively. In addition, we observed that serum Lp(a) concentrations were significantly lower in patients with type IV hyperlipidemia (mean 1.0 mg/dl [range 0.5-17], n = 16) than in normolipidemic patients (6.5 mg/dl [0.5-33.5], n = 117) and in type II hyperlipidemic patients (IIa 15.5 mg/dl [3.5-75], n = 13; IIb 9 mg/dl [1-80], n = 45); P < 0.001 by analysis of variance. CONCLUSIONS: Lp(a) concentrations were directly correlated with LDL cholesterol and negatively correlated with triglyceride levels in diabetic patients. Therefore, our results suggest that the treatment of diabetic dyslipemia may indirectly affect Lp(a) concentrations. PMID- 11213892 TI - Renin-angiotensin system gene polymorphisms, blood pressure, dyslipidemia, and diabetes in Hong Kong Chinese: a significant association of tne ACE insertion/deletion polymorphism with type 2 diabetes. AB - OBJECTIVE: In Chinese populations, hypertension is common and is a major risk factor for cerebrovascular and coronary heart disease, particularly when associated with diabetes. The clustering of these disorders and dyslipidemia and obesity is termed the metabolic syndrome and is increasing in prevalence in the populations of modernizing Asian nations. The renin-angiotensin system (RAS) helps maintain blood pressure and salt homeostasis and may play a role in the pathogenesis of aspects of the metabolic syndrome. We investigated three RAS gene polymorphisms--the ACE insertion/deletion (I/D), angiotensinogen (AGT) M235T, and angiotensin II type 1 receptor (AT1R) A1166C polymorphisms--for a possible role in modulating these disorders in 853 Chinese subjects with varying components of the metabolic syndrome. RESEARCH DESIGN AND METHODS: The three gene polymorphisms of this cross-sectional study were detected using polymerase chain reaction-based protocols. The genotype frequencies were compared between the controls (n = 119) and both overlapping and nonoverlapping groups of patients with type 2 diabetes, hypertension, and dyslipidemia using chi2 test. Differences in levels of the biochemical parameters between the genotypes were determined using analysis of variance. RESULTS: No significant relationship was identified between these polymorphisms and blood pressure in this population. Although the AT1RA1166C polymorphism was not associated with any aspect of the metabolic syndrome examined, there was limited evidence to suggest that the AGT M235T polymorphism may be associated with cholesterol levels. The ACE I allele was significantly more frequent in each group comprising subjects with type 2 diabetes/glucose intolerance (GIT), and the I allele was associated with higher fasting plasma glucose levels. CONCLUSIONS: These findings suggest that these polymorphisms are unlikely to be involved in the pathogenesis of hypertension. The ACE I/D polymorphism was associated with the metabolic syndrome, having a higher frequency of I allele-containing genotypes in those groups, but this appeared to result predominantly from the relationship with type 2 diabetes/GIT in this population of Chinese subjects. PMID- 11213893 TI - Homeostasis model assessment is a reliable indicator of insulin resistance during follow-up of patients with type 2 diabetes. AB - OBJECTIVE: To investigate the usefulness of the homeostasis model assessment as an index of insulin resistance (HOMA-IR) for evaluating the clinical course of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: The usefulness of HOMA-IR and its relationship with insulin resistance assessed by the hyperinsulinemic-euglycemic clamp study (clamp IR) were evaluated in 55 Japanese patients with type 2 diabetes before and after treatment. The patients were subjected to diet (approximately 1,440-1,720 kcal/day) and exercise therapy (walking 10,000 steps daily) for 6 weeks during their hospitalization. RESULTS: Univariate regression analysis disclosed a significant correlation between log transformed HOMA-IR and log-transformed clamp IR before (r = -0.613, P < 0.0001) and after ( = -0.734, P < 0.0001) treatment. Neither the slopes (-0.71 +/- 0.12 vs. -0.79 +/- 0.09, F = 0.25, P = 0.61) nor the intercepts (y-intercept = 1.67 vs. 1.70, x-intercept = 2.36 vs. 2.15, F = 0.02, P = 0.88) of the regression lines between HOMA-IR and clamp IR were significantly different before and after treatment. There was a significant correlation between the decrease in log transformed HOMA-IR and the increase in clamp IR during treatment (r = -0.617, P < 0.0001). CONCLUSIONS: HOMA-IR may constitute a useful method not only for diagnosing insulin resistance, but also for follow-up during the treatment of patients with type 2 diabetes. PMID- 11213894 TI - Changes in cognitive abilities over a 4-year period are unfavorably affected in elderly diabetic subjects: results of the Epidemiology of Vascular Aging Study. AB - OBJECTIVE: To compare 4-year changes in cognitive performance among elderly subjects according to category of fasting blood glucose (FBG) using American Diabetes Association criteria. RESEARCH DESIGN AND METHODS: Subjects without any detectable cognitive dysfunction were selected from the Epidemiology of Vascular Aging (EVA) Study, a cohort of community-dlwelling people aged 59-71 years at baseline. They were classified into glucose categories (normal, impaired fasting glucose [IFG], or diabetic) based on FBG values or known diabetes. Their cognitive abilities were assessed by a global test (Mini Mental Status Examination [MMSE]) and eight domain-specific tests, and they were reassessed 4 years later. Serious cognitive worsening was defined as a score evolution into the worst 15% of the sample's distribution of score differences (4-year score minus baseline score) for each test. RESULTS: At baseline, age-, sex-, and education-adjusted scores for all cognitive tests except one were similar across glucose categories. After 4 years, diabetic subjects had a lower performance on all tests except the MMSE, with differences reaching statistical significance on four tests. Adjusted odds ratios for serious worsening over 4 years in diabetic subjects, with reference to normal subjects, were >2 for four tests (P < 0.05) and bordering this value for two others (P < 0.09). Further adjustment for blood pressure or potential cognition-affecting substances (alcohol, tobacco, and medications) did not modify these results. CONCLUSIONS: Despite similar high initial cognitive function, diabetic subjects tended to have an unfavorable evolution of cognitive performance over 4 years compared with subjects who had normal glucose or IFG. PMID- 11213895 TI - Relationships of upper gastrointestinal motor and sensory function with glycemic control. AB - Acute changes in the blood glucose concentration have a major reversible effect on esophageal, gastric, intestinal, gallbladder, and anorectal motility in both healthy subjects and diabetic patients. For example, gastric emptying is slower during hyperglycemia than euglycemia and accelerated during hypoglycemia. Acute hyperglycemia also affects perceptions arising from the gastrointestinal tract and may accordingly, be important in the etiology of gastrointestinal symptoms in diabetes. Elevations in blood glucose that are within the normal postprandial range also affect gastrointestinal motor and sensory function. Upper gastrointestinal motor function is a critical determinant of postprandial blood glucose concentrations by influencing the absorption of ingested nutrients. Interventions that reduce postprandial hyperglycemia, by modulating the rate of gastric emptying, have the potential to become mainstream therapies in the treatment of diabetes. PMID- 11213896 TI - Renal gluconeogenesis: its importance in human glucose homeostasis. AB - Studies conducted over the last 60 years in animals and in vitro have provided considerable evidence that the mammalian kidney can make glucose and release it under various conditions. Until quite recently however, it was generally believed that the human kidney was not an important source of glucose except during acidosis and after prolonged fasting. This review will summarize early work in animals and humans, discuss methodological problems in assessing renal glucose release in vivo, and present results of recent human studies that provide evidence that the kidney may play a significant role in carbohydrate metabolism under both physiological and pathological conditions. PMID- 11213897 TI - Control of vascular cell proliferation and migration by PPAR-gamma: a new approach to the macrovascular complications of diabetes. AB - Compared with nondiabetic subjects, type 2 diabetic individuals are at an increased risk for coronary artery disease and coronary restenosis after angioplasty or stenting. Increased proliferation and migration of vascular smooth muscle cells (VSMCs) contribute importantly to the formation of both atherosclerotic and restenotic lesions. Therefore, pharmaceutical interventions targeting proteins that regulate VSMC growth or movement are a promising new approach to treat diabetes-associated cardiovascular disease. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of the nuclear receptor superfamily that, when activated by thiazolidinedione (TZD) insulin sensitizers, regulates a host of target genes. All of the major cells in the vasculature express PPAR-gamma, including endothelial cells, VSMCs, and monocytes/macrophages. PPAR-gamma is present in intimal macrophages and VSMCs in early human atheromas. In an animal model of vascular injury; PPAR-gamma levels are substantially elevated in the neointima that forms after mechanical injury of the endothelium. Recent experimental studies provide evidence that PPAR-gamma may function to protect the vasculature from injury. Cell culture studies have shown that TZD PPAR-gamma ligands inhibit both the proliferation and migration of VSMCs. These antiatherogenic activities of PPAR-gamma may also occur in vivo, because TZDs inhibit lesion formation in several animal models. PPAR-gamma ligands may also protect the vasculature indirectly by normalizing metabolic abnormalities of the diabetic milieu that increase cardiovascular risk. Activation of PPAR-gamma, newly defined in vascular cells, may be a useful approach to protect the vasculature in diabetes. PMID- 11213898 TI - Proposed guidelines on screening for risk of type 1 diabetes. PMID- 11213899 TI - American Diabetes Association 60th Scientific Sessions, 2000: cardiovascular disease in diabetes. PMID- 11213900 TI - Reduction in foot ulcer incidence: relation to compliance with a prophylactic foot care program. PMID- 11213901 TI - Depression among African-Americans with diabetes: a dearth of studies. PMID- 11213902 TI - Evidence of autoimmunity in male twins with neonatal diabetes. PMID- 11213903 TI - Does pioglitazone, like troglitazone, increase serum levels of lipoprotein(a) in diabetic patients? PMID- 11213904 TI - Efficacy of oral sildenafil in the treatment of erectile dysfunction in diabetic men with positive response to intracavernosal injection of alprostadil. PMID- 11213905 TI - Treatment with human analog (GlyA21, ArgB31, ArgB32) insulin glargine (HOE901) resolves a generalized allergy to human insulin in type 1 diabetes. PMID- 11213906 TI - The continuing increase of diabetes in the US. PMID- 11213907 TI - Cost-free prevention to asymptomatic bacteriuria in diabetic women: two hands, two towels. PMID- 11213908 TI - Catch-22. PMID- 11213910 TI - Studies on the biological effects of ozone: 11. Release of factors from human endothelial cells. AB - BACKGROUND: Empirical observations have shown that ozonated autohemotherapy markedly improves the symptoms of chronic limb ischemia (muscular pain at rest, intermittent claudication, etc) in atherosclerotic patients, but mechanisms of action remain unclear. AIMS: Human endothelial cells (HUVECs) are known to release nitrogen monoxide (NO) and we investigated the biological effects of human ozonated serum on HUVECs in culture. METHODS: We assessed the relevance of peroxidation, the release of NO as nitrite and of three classical cytokines. RESULTS: The treatment of HUVECs with ozonated serum yields a dose dependent increase of thiobarbituric acid reactive substances (TBARS) and of hydrogen peroxide (H2O2) and a decrease of protein thiol groups (PTG). Concomitantly, in comparison to either the control or the oxygenated sample, there is a significant and steady increase of nitric oxide (NO) production; this is markedly enhanced by the addition of L-arginine (20 microM) and inhibited in the presence of the NO inhibitor, L-NAME (20 mM). The main mediator of ozone action is H2O2 as it has been shown either after its direct measurement or by the addition of 20, 40 and 100 microM. Moreover, during 24 hours incubation we have investigated the production of endothelin 1 (ET-1), E-selectin and Interleukin 8 (IL-8) and it appears that ozonation enhances IL-8, inhibits E-selectin and hardly modifies ET 1 production. CONCLUSIONS: It appears that reinfusion of ozonated blood, by enhancing release of NO, may induce vasodilation in ischemic areas and reduce hypoxia. PMID- 11213909 TI - Role of cytokines and nitric oxide in the induction of tuberculostatic macrophage functions. AB - The aim of this study was to determine phenotypic differences when BCG invades macrophages. Bacilli prepared from the same BCG primary seed, but produced in different culture media, were analysed with respect to the ability to stimulate macrophages and the susceptibility to treatment with cytokines and nitric oxide (NO). Tumour necrosis factor (TNF) activity was assayed by measuring its cytotoxic activity on L-929 cells, interleukin-6 (IL-6) and interferon-gamma (IFN gamma) were assayed by enzyme-linked immunosorbent assay (ELISA), whereas NO levels were detected by Griess colorimetric reactions in the culture supernatant of macrophages incubated with IFN-gamma, TNF or NO and subsequently exposed to either BCG-I or BCG-S. We found that BCG-I and BCG-S bacilli showed different ability to simulate peritoneal macrophages. Similar levels of IL-6 were detected in stimulated macrophages with lysate from two BCG samples. The highest levels of TNF and IFN-gamma were observed in macrophages treated with BCG-S and BCG-I, respectively. The highest levels of NO were observed in cultures stimulated for 48 h with BCG-S. We also found a different susceptibility of the bacilli to exogenous treatment with IFN-gamma and TNF which were capable of killing 60 and 70% of both bacilli, whereas NO was capable of killing about 98 and 47% of BCG-I and BCG-S, respectively. The amount of bacilli proportionally decreased with IFN gamma and TNF, suggesting a cytokine-related cytotoxic effect. Moreover, NO also decreased the viable number of bacilli. Interestingly, NO levels of peritoneal macrophages were significantly increased after cytokine treatment. This indicates that the treatment of macrophages with cytokines markedly reduced bacilli number and presented effects on NO production. The results obtained here emphasize the importance of adequate stimulation for guaranteeing efficient killing of bacilli. In this particular case, the IFN-gamma and TNF were involved in the activation of macrophage bactericidal activity. PMID- 11213911 TI - ATP induced MUC5AC release from human airways in vitro. AB - BACKGROUND: Chronic airway diseases are often associated with marked mucus production, however, little is known about the regulation of secretory activity by locally released endogenous mediators. AIM: This investigation was performed to determine the release of MUC5AC mucin from human bronchial preparations using the purinergic agonists adenosine 5'-triphosphate (ATP) and uridine 5' triphosphate (UTP). METHODS: Immunohistochemical and immunoradiometric assays (IRMA) were used to detect the MUC5AC mucin. Immunohistochemical analysis were performed using individual 1-13 M1 and 21 M1 MAbs recognizing a recombinant M1 mucin partially encoded by the MUC5AC gene. IRMA measurments were performed using a mixture of eight anti-M1 mucin MAbs (PM8), which included both 1-13 M1 and 21 M1 MAbs. Lysozyme and protein were also measured in the biological fluids derived from human bronchial preparations obtained from patients who had undergone surgery for lung carcinoma. RESULTS: The anti-M1 monoclonal antibodies labelled epithelial goblet cells. After challenge of human bronchial preparations with ATP, the goblet cells exhibited less staining. In contrast, UTP did not alter the immunolabelling of goblet cells. MUC5AC mucin in the bronchial fluids derived from ATP-challenged preparations was increased while UTP had no effect on release. ATP did not alter either the quantities of lysozyme or protein detected in the biological fluids. CONCLUSION: These results suggest that ATP may regulate epithelial goblet cell secretion of MUC5AC mucin from human airways in vitro. PMID- 11213912 TI - Sera from patients with sepsis induce nitric oxide production in vascular smooth muscle cells. AB - BACKGROUND: Nitric oxide (NO) is an important physiological mediator of vascular tone and is involved in pathophysiology of septic shock. Although plasma nitrite is a stable end product of NO oxidation derived from endogenous NO, the plasma nitrite level is also easily affected by the intake of various foods, bacterial products and renal functional status. AIMS: We propose an excellent alternative assay technique for measuring endogenous NO production. METHODS: We measured the nitrite level in cultured vascular smooth muscle cells (SMC) treated with serum obtained from patients with sepsis (4 patients), by means of a chemiluminescence detector. RESULTS: The nitrite concentrations in such cells were significantly higher as compared to those in the cells treated with normal serum. Moreover, the increased nitrite levels in the SMC treated with the sera obtained from patients with sepsis were completely inhibited by L-nitroarginine (1 mmol/L), a nitric oxide synthase inhibitor. CONCLUSION: These data suggest that this assay method enable us to know the ability of endogenous NO production in each patient. PMID- 11213914 TI - Diagnostic ultrasound should be performed without upper intensity limits. PMID- 11213913 TI - IL-12, IL-6 and IFN-gamma production by lymphocytes of pregnant women with rheumatoid arthritis remission during pregnancy. AB - BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease with progressive activity. The RA remission was observed in women during pregnancy, but the mechanism responsible for remission is hypothetical only and concerns mechanisms of immune regulation such as lymphocyte subpopulations and interleukin production. AIMS: The lymphocyte subpopulations and interleukin production in vitro in a group of healthy non-pregnant women, healthy pregnant women and pregnant women suffering from RA may help towards a better understanding of regulation of the immune processes. METHODS: The investigations were performed in trimester III--2 days after delivery and 6 weeks after delivery. Peripheral blood lymphocytes were isolated on Gradisol gradient and analysed immediately or after having been cultured for 72 hours in RPMI medium supplemented with 10% FCS. The cultures were terminated after 72 h, supernatants stored at -72 degrees C for interleukin evaluation. The concentrations of IFN-gamma, IL-2, IL-6, IL-12, TNF alpha and its soluble receptors R-I, R-II were estimated in non-stimulated and PHA (Sigma, 5 microg/ml) stimulated culture supernatants using ELISA Endogen kits according to the manufacturer's instructions. RESULTS: The general pattern of T cell subpopulation distribution was similar in all analysed groups. Decreased IFN gamma, IL-12 and increased IL-6 production by lymphocytes after PHA stimulation was found in trimester III in pregnant women with RA as compared to healthy pregnant woman. CONCLUSION: The obtained results suggest that in pregnant women with RA the TH1 cell response predominates, contrary to healthy pregnant women with TH2 type functional response. These phenomena were not observed after delivery. PMID- 11213915 TI - Control of interstitial thermal coagulation: comparative evaluation of microwave and ultrasound applicators. AB - This study presents a comparative evaluation of the control of heating and thermal coagulation with microwave (MW) and ultrasound (US) interstitial applicators. Helical coil MW antennas (17 mm and 25 mm length radiating antennae) were tested using an external implant catheter (2.2 mm o.d.) with water-cooling. US applicators with tubular transducers (2.2 and 2.5 mm o.d., 10 mm length, single-element and 3-element) were utilized with a direct-coupled configuration and internal water-cooling. Measurements of E-field distributions (for MW) and acoustic beam distributions (for US) were used to characterize the applicator energy output. Thermal performance was evaluated through multiple heating trials in vitro (bovine liver) and in vivo (porcine thigh muscle and liver) at varied levels of applied power (20-40 W for microwave, 15-35 W for ultrasound) and heating times (0.5-5 min). Axial temperature distributions in the tissue were recorded during heating, and dimensions of the resulting lesions of thermal coagulation were measured. Both MW and US applicators produced large volumes of tissue coagulation ranging from 8 to 20 cm3 with singular heating times of 5 min. Radial depth of lesions for both MW and US applicators increased with heating duration and power levels, though US produced notably larger lesion diameters (30 42 mm for US vs 18-26 mm for MW, 5 min heating). Characteristic differences between the applicators were observed in axial energy distribution, tissue temperatures, and thermal lesion shapes. MW lesions increased significantly in axial dimensions (beyond the active applicator length) as applied power level and/or heating duration was increased, and lesion shapes were generally not uniform. US provided greater control and uniformity of heating, with energy deposition and axial extent of thermal lesions corresponding to the length of the active transducer(s). The improved ability to control the extent of thermal coagulation demonstrated by the US applicators provides greater potential to target a specific region of tissue. PMID- 11213916 TI - Threshold contrast detail detectability measurement of the fluoroscopic image quality of a dynamic solid-state digital x-ray image detector. AB - Solid-state digital x-ray imaging detectors of flat-panel construction will play an increasingly important role in future medical imaging facilities. Solid-state detectors that will support both dynamic (including fluoroscopic) and radiographic image recording are under active development. The image quality of an experimental solid-state digital x-ray image detector operating in a continuous fluoroscopy mode has been investigated. The threshold contrast detail detectability (TCDD) technique was used to compare the fluoroscopic imaging performance of an experimental dynamic solid-state digital x-ray image detector with that of a reference image intensifier television (IITV) fluoroscopy system. The reference system incorporated Plumbicon TV. Results were presented as a threshold detection index, or H(T)(A), curves. Measurements were made over a range of mean entrance air kerma (EAK) rates typically used in conventional IITV fluoroscopy. At the upper and mid EAK rate range (440 and 220 nGy/s) the solid state detector outperformed the reference IITV fluoroscopy system as measured by TCDD performance. At the lowest measured EAK rate (104 nGy/s), the solid-state detector produces slightly inferior TCDD performance compared with the reference system. Although not statistically significant at this EAK rate, the difference will increase as EAK is lowered further. Overall the TCDD results and early clinical experiences support the proposition that a current design of dynamic solid-state detector produces image quality competitive with that of modern IITV fluoroscopy systems. These findings encourage the development of compact and versatile universal x-ray imaging systems based upon solid-state detector technology to support R & F and vascular/interventional applications. PMID- 11213917 TI - Comparison of in-phantom dose distributions for coronary angiography using an x ray machine and synchrotron radiation. AB - Coronary cineangiography using synchrotron radiation is anticipated, owing to the high intensity and availability of monoenergy. To investigate allowable dose levels in clinical application, absorbed dose distribution in a tissue substitute phantom for a conventional x-ray machine was measured with thermoluminescent dosimeters at the University of Tsukuba under the practical conditions used for digital angiography. The dose rate at a 0.5-cm depth was 0.145 Gy/s, and the dose per frame was 0.725 mGy for the irradiation period of 5 ms per frame. For synchrotron radiation, the dose distribution measurement was made at a 5-GeV AR (Accumulation Ring) of the High Energy Accelerator Research Organization, in which a polymethylmethacrylate (PMMA) phantom was irradiated with the strongest beam available at the facility, which was 33.32 keV, 5.2 x 6.2 cm2 beam. Using this beam, a 1-mm-diameter coronary artery has been visualized at 1% iodine concentration at the AR. Nonhomogeneous strength distribution in the beam was observed in the vertical direction. The maximum dose rate was 0.556 Gy/s, and it attenuated to 1/3000 at a 30-cm depth in the beam center. At the deep positions, the doses were influenced by the high harmonics, which was confirmed with an EGS4 Monte Carlo calculation. Outside the beam, beam contamination on both sides of the main beam affected the doses. For comparison to the x-ray machine, the measured dose was analytically converted to that needed for a 5.2 x 16 cm2 beam that is used for clinical application. The dose rate at 0.5-cm depth was found to be 0.215 Gy/s, which is 1.48 times larger than that for x-rays. Moreover, the attenuation rate in the phantom was significantly greater than that of the x-ray machine, because of the difference of the energy spectra between the x-rays and synchrotron radiation used. PMID- 11213918 TI - Processing of medical images using real-time optical Fourier processing. AB - Optical image processing techniques are inherently fast in view of parallel processing. A self-adaptive optical Fourier processing system using photoinduced dichroism in a bacteriorhodopsin film was experimentally demonstrated for medical image processing. Application of this powerful analog all-optical interactive technique for cancer diagnostics is illustrated with two mammograms and a Pap smear. Microcalcification clusters buried in surrounding tissue showed up clearly in the processed image. By playing with one knob, which rotates the analyzer in the optical system, either the microcalcification clusters or the surrounding dense tissue can be selectively displayed. Bacteriorhodopsin films are stable up to 140 degrees C and environmentally friendly. As no interference is involved in the experiments, vibration isolation and even a coherent light source are not required. It may be possible to develop a low-cost rugged battery operated portable signal-enhancing magnifier. PMID- 11213919 TI - Fast acceleration-encoded magnetic resonance imaging. AB - Direct acceleration imaging with high spatial resolution was implemented and tested. The well-known principle of phase encoding motion components was applied. Suitable gradient switching provides a signal phase shift proportional to the acceleration perpendicular to the slice in the first scan of the sequences. An additional scan serving as a reference was recorded for compensation of phase effects due to magnetic field inhomogeneities. The first scan compensated for phase shifts from undesired first- and second-order motions; the second scan was completely insensitive to velocity and acceleration in all directions. Advantages of the proposed two-step technique compared to former approaches with Fourier acceleration encoding (with several phase encoding steps) are relatively short echo times and short total measuring times. On the other hand, the new approach does not allow us to assess the velocity or acceleration spectrum simultaneously. The capabilities of the sequences were tested on a modern 1.5 T whole body MR unit providing relatively high gradient amplitudes (25 mT/m) and short rise times (600 micros to maximum amplitude). The results from a mechanical acceleration phantom showed a standard deviation of 0.3 m/s2 in sequences with an acceleration range between -12 and 12 m/s2. This range covers the expected maximum acceleration in the human aorta of 10 m/s2. Further tests were performed on a stenosis phantom with a variable volume flow rate to assess the flow characteristics and possible displacement artifacts of the sequences. Preliminary examinations of volunteers demonstrate the potential applicability of the technique in vivo. PMID- 11213920 TI - Device-dependent activity estimation and decay correction of radionuclide mixtures with application to Tc-94m PET studies. AB - Multi-instrument activity estimation and decay correction techniques were developed for radionuclide mixtures, motivated by the desire for accurate quantitation of Tc-94m positron emission tomography (PET) studies. Tc-94m and byproduct Tc isotopes were produced by proton irradiation of enriched Mo-94 and natural Mo targets. Mixture activities at the end of bombardment were determined with a calibrated high purity germanium detector. The activity fractions of the greatest mixture impurities relative to 100% for Tc-94m averaged 10.0% (Tc-94g) and 3.3% (Tc-93) for enriched targets and 10.1% (Tc-94g), 11.0% (Tc-95), 255.8% (Tc-96m), and 7.2% (Tc-99m) for natural targets. These radioisotopes have different half-lives (e.g., 52.5 min for Tc-94m, 293 min for Tc-94g), positron branching ratios (e.g., 0.72 for Tc-94m, 0.11 for Tc-94g) and gamma ray emissions for themselves and their short-lived, excited Mo daughters. This complicates estimation of injected activity with a dose calibrator, in vivo activity with PET and blood sample activity with a gamma counter. Decay correction using only the Tc-94m half-life overestimates activity and is inadequate. For this reason analytic formulas for activity estimation and decay correction of radionuclide mixtures were developed. Isotope-dependent sensitivity factors for a PET scanner, dose calibrator, and gamma counter were determined using theoretical sensitivity models and fits of experimental decay curves to sums of exponentials with fixed decay rates. For up to 8 h after the end of bombardment with activity from enriched and natural Mo targets, decay-corrected activities were within 3% of the mean for three PET studies of a uniform cylinder, within 3% of the mean for six dose calibrator decay studies, and within 6% of the mean for four gamma counter decay studies. Activity estimation and decay correction for Tc-94m mixtures enable routine use of Tc-94m in quantitative PET, as illustrated by application to a canine Tc-94m sestamibi study. PMID- 11213921 TI - Scanning microwave-induced thermoacoustic tomography: signal, resolution, and contrast. AB - Scanning thermoacoustic tomography was explored in the microwave region of the electromagnetic spectrum. Short microwave pulses were used to induce acoustic waves by thermoelastic expansion in biological tissues. Cross sections of tissue samples were imaged by a linear scan of the samples while a focused ultrasonic transducer detected the time-resolved thermoacoustic signals. Based on the microwave-absorption properties of normal and cancerous breast tissues, the piezoelectric signals in response to the thermoacoustic contrast were investigated over a wide range of electromagnetic frequencies and depths of tumor locations. The axial resolution is related to the temporal profile of the microwave pulses and to the impulse response of the ultrasonic transducer. The lateral resolution is related to the numerical aperture of the ultrasonic transducer as well as to the frequency spectra of the piezoelectric signals in the time window corresponding to the axial resolution. Gain compensation, counteracting the microwave attenuation, was applied to enhance the image contrast. PMID- 11213922 TI - Reference dosimetry in clinical high-energy photon beams: comparison of the AAPM TG-51 and AAPM TG-21 dosimetry protocols. AB - Task Group 51 (TG-51) of the Radiation Therapy Committee of the American Association of Physicists in Medicine (AAPM) has recently developed a new protocol for the calibration of high-energy photon and electron beams used in radiation therapy. The formalism and the dosimetry procedures recommended in this protocol are based on the use of an ionization chamber calibrated in terms of absorbed dose-to-water in a standards laboratory's 60Co gamma ray beam. This is different from the recommendations given in the AAPM TG-21 protocol, which are based on an exposure calibration factor of an ionization chamber in a 60Co beam. The purpose of this work is to compare the determination of absorbed dose-to water in reference conditions in high-energy photon beams following the recommendations given in the two dosimetry protocols. This is realized by performing calibrations of photon beams with nominal accelerating potential of 6, 18 and 25 MV, generated by an Elekta MLCi and SL25 series linear accelerator. Two widely used Farmer-type ionization chambers having different composition, PTW 30001 (PMMA wall) and NE 2571 (graphite wall), were used for this study. Ratios of AAPM TG-51 to AAPM TG-21 doses to water are found to be 1.008, 1.007 and 1.009 at 6, 18 and 25 MV, respectively when the PTW chamber is used. The corresponding results for the NE chamber are 1.009, 1.010 and 1.013. The uncertainties for the ratios of the absorbed dose determined by the two protocols are estimated to be about 1.5%. A detailed analysis of the reasons for the discrepancies is made which includes comparing the formalisms, correction factors and quantities in the two protocols, as well as the influence of the implementation of the different standards for chamber calibration. The latter has been found to have a considerable influence on the differences in clinical dosimetry, even larger than the adoption of the new data and recommended procedures, as most intrinsic differences cancel out due to the adoption of the new formalism. PMID- 11213923 TI - Modeling the extrafocal radiation and monitor chamber backscatter for photon beam dose calculation. AB - A simple analytical approach has been developed to model extrafocal radiation and monitor chamber backscatter for clinical photon beams. Model parameters for both the extrafocal source and monitor chamber backscatter are determined simultaneously using conventional measured data, i.e., in-air output factors for square and rectangular fields defined by the photon jaws. The model has been applied to 6 MV and 15 MV photon beams produced by a Varian Clinac 2300C/D accelerator. Contributions to the in-air output factor from the extrafocal radiation and monitor chamber backscatter, as predicted by the model, are in good agreement with the measurements. The model can be used to calculate the in-air output factors analytically, with an accuracy of 0.2% for symmetric or asymmetric rectangular fields defined by jaws when the calculation point is at the isocenter and 0.5% when the calculation point is at an extended SSD. For MLC-defined fields, with the jaws at the recommended positions, calculated in-air output factors agree with the measured data to within 0.3% at the isocenter and 0.7% at off-axis positions. The model has been incorporated into a Monte Carlo dose algorithm to calculate the absolute dose distributions in patients or phantoms. For three MLC-defined irregular fields (triangle shape, C-shape, and L-shape), the calculations agree with the measurements to about 1% even for points at off axis positions. The model will be particularly useful for IMRT dose calculations because it accurately predicts beam output and penumbra dose. PMID- 11213924 TI - Leaf position error during conformal dynamic arc and intensity modulated arc treatments. AB - Conformal dynamic arc (CD-ARC) and intensity modulated arc treatments (IMAT) are both treatment modalities where the multileaf collimator (MLC) can change leaf position dynamically during gantry rotation. These treatment techniques can be used to generate complex isodose distributions, similar to those used in fix gantry intensity modulation. However, a beam-hold delay cannot be used during CD ARC or IMAT treatments to reduce spatial error. Consequently, a certain amount of leaf position error will have to be accepted in order to make the treatment deliverable. Measurements of leaf position accuracy were taken with leaf velocities ranging from 0.3 to 3.0 cm/s. The average and maximum leaf position errors were measured, and a least-squares linear regression analysis was performed on the measured data to determine the MLC velocity error coefficient. The average position errors range from 0.03 to 0.21 cm, with the largest deviations occurring at the maximum achievable leaf velocity (3.0 cm/s). The measured MLC velocity error coefficient was 0.0674 s for a collimator rotation of 0 degrees and 0.0681 s for a collimator rotation of 90 degrees. The distribution in leaf position error between the 0 degrees and 90 degrees collimator rotations was within statistical uncertainty. A simple formula was developed based on these results for estimating the velocity-dependent dosimetric error. Using this technique, a dosimetric error index for plan evaluation can be calculated from the treatment time and the dynamic MLC leaf controller file. PMID- 11213925 TI - Experimental validation of dose calculation algorithms for the GliaSite RTS, a novel 125I liquid-filled balloon brachytherapy applicator. AB - This paper compares experimentally measured and calculated dose-rate distributions for a novel 125I liquid-filled brachytherapy balloon applicator (the GliaSite RTS), designed for the treatment of malignant brain-tumor resection cavity margins. This work is intended to comply with the American Association of Physicists in Medicine (AAPM) Radiation Therapy Committee's recommendations [Med. Phys. 25, 2269-2270 (1998)] for dosimetric characterization of low-energy photon interstitial brachytherapy sources. Absolute low dose-rate radiochromic film (RCF) dosimetry measurements were performed in coronal planes about the applicator. The applicator was placed in a solid water phantom, machined to conform to the inflated applicator's surface. The results were used to validate the accuracy of Monte Carlo photon transport (MCPT) simulations and a point source dose-kernel algorithm in predicting dose to water. The absolute activity of the 125I solution was determined by intercomparing a National Institute of Standards and Technology (NIST) 125I standard with a known mass of radiotherapy solution (Iotrex) in an identical vial and geometry. For the two films not in contact with applicator, the average agreement between RCF and MCPT (specified as the mean absolute deviation in successive 4 mm rings) was found to be within +/ 5% at distances 0.2-25 mm from the film centers. For the two films touching the catheter, the mean agreement was +/-14.5% and 7.5% near the balloon surface but improving to 7.5% and 6% by 3.5 mm from the surface. These errors, as large as 20% in isolated pixels, are likely due to trim damage, 125I contamination, and poor conformance with the balloon. At larger distances where the radiation doses were very low, the observed discrepancies were significantly larger than expected. We hypothesize that they are due to a dose-rate dependence of the RCF response. A 1%-10% average difference between a simple one-dimensional path length semiempirical dose-kernel model and the MCPT calculations was observed over clinically relevant distances. PMID- 11213926 TI - Dose rate constant and energy spectrum of interstitial brachytherapy sources. AB - In the past two years, several new manufacturers have begun to market low-energy interstitial brachytherapy seeds containing 125I and 103Pd. Parallel to this development, the National Institute of Standards and Technology (NIST) has implemented a modification to the air-kerma strength (S(K)) standard for 125I seeds and has also established an S(K) standard for 103Pd seeds. These events have generated a considerable number of investigations on the determination of the dose rate constants (inverted V) of interstitial brachytherapy seeds. The aim of this work is to study the general properties underlying the determination of dose rate constant and to develop a simple method for a quick and accurate estimation of dose rate constant. As the dose rate constant of clinical seeds is defined at a fixed reference point, we postulated that dose rate constant may be calculated by treating the seed as an effective point source when the seed's source strength is specified in S(K) and its source characteristics are specified by the photon energy spectrum measured in air at the reference point. Using a semi-analytic approach, an analytic expression for dose rate constant was derived for point sources with known photon energy spectra. This approach enabled a systematic study of dose rate constant as a function of energy. Using the measured energy spectra, the calculated dose rate constant for 125I model 6711 and 6702 seeds and for 192Ir seed agreed with the AAPM recommended values within +/-1%. For the 103Pd model 200 seed, the agreement was 5% with a recently measured value (within the +/-7% experimental uncertainty) and was within 1% with the Monte Carlo simulations. The analytic expression for dose rate constant proposed here can be evaluated using a programmable calculator or a simple spreadsheet and it provides an efficient method for checking the measured dose rate constant for any interstitial brachytherapy seed once the energy spectrum of the seed is known. PMID- 11213927 TI - A dose texture plot in a moving frame as a new planning tool for single-plane implants in HDR brachytherapy. AB - A dose-texture plot is a print of dose values on the points of interest in a super-plane. The super-plane is a moving frame across the treatment depth surface(s) with a fixed distance from surgical bed. The moving frame has an axis tangent to the midline of two neighboring catheters and the other axis perpendicular to the midline. By setting the scales of the two axes in units of the dwell step-size and the local distance between the two catheters, we can easily locate the basal-dose points with pairs of integers. A dose-texture plot on the basal-dose points in the super-plane provides the dose and location information in one picture. Such a picture can concisely represent the dose distribution in the treatment depth and allows us to quickly and quantitatively evaluate the effect of the source-dwell times and positions. This treatment planning-evaluation tool has been used for development of an iteration optimization algorithm. The results of the iteration optimization on clinical cases demonstrated significant improvements over the optimization algorithms used in a commercial planning system. PMID- 11213928 TI - The nontoxic tripeptide glycyl-prolyl-glycine amide inhibits the replication of human immunodeficiency virus type 1. AB - OBJECTIVE: To determine whether short peptides corresponding to the RGPGR motif of the V3 loop of gp 120 have anti-human immunodeficiency virus type 1 (anti-HIV 1) activity. DESIGN/METHODS: Short peptides were tested against the HIV-1 laboratory strains and clinical isolates. RESULTS: The tripeptide glycyl-prolyl glycine amide (GPG-NH2) inhibited the replication of both laboratory strains and 47 clinical isolates, including 19 strains that were resistant to other drugs or that were from patients with failing therapy. The 50% inhibitory concentrations values were 2.7 to 37 microM. Phenotypic change of two isolates from nonsyncytia inducing to syncytia-inducing did not change their sensitivity to GPG-NH2. The tripeptide added to the antiviral effect of both zidovudine and ritonavir. CONCLUSIONS: The tripeptide GPG-NH2 is a nontoxic compound that inhibits the replication of HIV-1 by an apparently new mode of action. Glycyl-prolyl-glycine NH2 might prove useful by itself or as a lead compound for the treatment of drug resistant HIV-1. Glycyl-prolyl-glycine-NH2 is currently undergoing phase I/II human clinical trials in Sweden. PMID- 11213929 TI - Differences in perinatal transmission among human immunodeficiency virus type 1 genotypes. AB - OBJECTIVE: To determine whether genotypes from human immunodeficiency virus type 1 (HIV-1) subtypes A, C, or D or intersubtype recombinants have the same probability of being transmitted from mother to child. METHODS: We determined the HIV-1 genetic subtype and maternal risk factors of 51 matched transmitting and nontransmitting mothers from Tanzania. The HIV-1 gag (p24-p7) and env (C2-C5) nucleotide sequences were used for genotype classification, and matched logistic regression analysis was used to assess differences among genotypes. RESULTS: Mothers infected with HIV-1 subtype A (odds ratio, 3.8; 95% CI, 0.8-24.7%), HIV-1 subtype C (odds ratio, 5.1; 95% CI, 1.3-30.8%), or HIV-1 intersubtype recombinant viruses (odds ratio, 5.3; 95% CI, 1.2-33.4%) were more likely to transmit HIV-1 to their infants than mothers infected with HIV-1 subtype D. Lower CD4 cell counts at enrollment were associated with transmission, but CD4 cell counts within each genotype did not explain differences in transmission among HIV-1 genotypes. CONCLUSION: We have shown that HIV-1 genotypes might be associated with differential risk for vertical transmission. These findings provide the first evidence that HIV-1 genetic subtypes may play a role in rates of vertical transmission in an African setting. PMID- 11213930 TI - The product of human cytomegalovirus UL73 is a new polymorphic structural glycoprotein (gpUL73). AB - OBJECTIVES: This work focuses on human cytomegalovirus (HCMV) UL73, which encodes for a putative transmembrane glycoprotein that is highly conserved among herpesviruses. STUDY DESIGN: pUL73 expression was analyzed both in transiently transfected and in HCMV-infected cells using a pUL73-specific antiserum by immunoblot and immunofluorescence. Sequencing analysis from several clinical isolates and laboratory-adapted strains was also performed. RESULTS: pUL73 expressed in transiently transfected cells consists in a polypeptide of the expected size (15-18 kd) with cytoplasmic localization. In infected cells, pUL73 is expressed with true-late kinetics and localizes both in perinuclear granular formations and on the cell surface. A broad band (39-53 kd), sensitive to O glycosidase digestion was detected in purified virus. In addition, sequence analysis showed that the N-terminal portion of pUL73 from clinical isolates is highly polymorphic. CONCLUSIONS: UL73 encodes for a new structural glycoprotein (gpUL73) expressed on the cell surface of infected cells and highly polymorphic among clinical isolates. PMID- 11213931 TI - Prevalence of drug resistance mutations in B, non-B subtypes, and recombinant forms of human immunodeficiency virus type 1 in infected individuals in Spain (Galicia). PMID- 11213932 TI - Human immunodeficiency virus (HIV)-specific immune responses are generated with the simultaneous vaccination of a gp120-depleted, whole-killed HIV-1 immunogen with cytosine-phosphorothioate-guanine dinucleotide immunostimulatory sequences of DNA. AB - OBJECTIVES: We compared the effect of priming with a synthetic oligodeoxynucleotide (ODN) immunostimulatory DNA sequence followed by vaccination with human immunodeficiency virus type 1 (HIV-1) in incomplete Freund's adjuvant (IFA) or HIV-1 antigen alone to the simultaneous administration of immunostimulatory sequences (ISS) with HIV-1 in IFA. METHODS: We examined immune function involving interferon-gamma (IFN-gamma) production, RANTES (regulated upon activation, normal T cell expressed and secreted) production, and lymphocyte proliferation, all of which appear to be augmented in HIV-1-exposed, but uninfected, individuals. RESULTS: We demonstrate that similar levels of antigen specific IFN-gamma were produced from lymph node cells of the animals immunized with HIV-1 antigen in IFA containing the CpG ODN 1826 (ISS; mean +/- SE = 450.8 +/- 224.3 pg/mL) and the group of animals primed with the ODN before injection with the HIV-1 in IFA (mean +/- SE = 377.7 +/- 294.8 pg/mL) or HIV-1 antigen alone (IFN-gamma = 0 pg/mL). However, the group that received the HIV-1 in IFA plus ISS mounted a stronger lymphocyte proliferation (mean net +/- SE = 29,180 +/ 1,932 cpm) compared to the group primed with the ODN before injection with HIV-1 in IFA (mean net +/- SE = 8,575 +/- 2,978 cpm). Furthermore, the group that received the HIV-1 in IFA plus ISS also mounted stronger beta-chemokine production measured as RANTES (mean +/- SE = 1,217 +/- 267.4 pg/mL) compared to the group that received the ODN before injection with HIV-1 in IFA (mean +/- SE = 129.1 +/- 48.5 pg/mL). Antibody responses from the group that received the HIV-1 in IFA plus ISS also showed a higher p24-specific response that was predominantly of the immunoglobulin G IgG2b isotype. CONCLUSION: These results suggest that the simultaneous administration of the ISS in the HIV-1 in IFA emulsion may be a condidate for testing in non-human primates and in human studies as a therapeutic and preventative vaccine. PMID- 11213933 TI - A bereavement support group intervention affects plasma burden of human immunodeficiency virus type 1. Report of a randomized controlled trial. AB - OBJECTIVES: This study investigates the potential impact of a bereavement support group on plasma viral load. METHODS: A randomly selected subsample of human immunodeficiency virus type 1 (HIV-1)-positive homosexual men participating in a controlled clinical trial of a bereavement support group intervention was studied. The intervention consisted of one 90-minute group session per week for 10 weeks. The plasma HIV-1 RNA copy number was measured at baseline and after intervention (10 weeks) by the Roche AMPLICOR assay. RESULTS: There was a significant effect of the intervention on the change on the plasma HIV-1 RNA copy number (limited control model, beta = -0.49, p = 0.02; extended control model, beta = -0.37, p = 0.01), independent of antiretroviral therapies; prophylactic therapies against potentially lethal HIV-1 associated conditions; CD4 cell count; viral load; and Centers for Disease Control and Prevention clinical disease stage at baseline. CONCLUSIONS: Bereavement support group interventions may prove to be not only a primary therapy for psychologic distress after bereavement but also an adjunctive therapy for sustained control of plasma viral load in conjunction with highly active antiretroviral therapy in this population. PMID- 11213934 TI - The tripeptide glycyl-prolyl-glycine amide does not affect the early steps of the human immunodeficiency virus type 1 replication. AB - OBJECTIVE: To determine whether the peptide glycyl-prolyl-glycine amide (GPG-NH2) corresponding to a conserved motif in the tip of the third hypervariable region of gp120 affected the early events in the human immunodeficiency virus type 1 (HIV-1) replication. DESIGN/METHODS: Glycyl-prolyl-glycine amide was tested for its effect on HIV-1 adsorption, co-receptor usage, proviral DNA synthesis, messenger RNA (mRNA) synthesis and splicing, translation, tat/TAR transactivation, and virus protease activity. RESULTS: Glycyl-prolyl-glycine amide did not appear to affect the early events of the virus replication. HIV-1 having glycine-leucine-glycine instead of GPG in the V3 loop and the mutants deleted of the GPG motif were still inhibited by the peptide. Glycyl-prolyl glycine-NH2 had no discernible effect on any of the other steps in the virus replication cycle tested. The only effect observed was an increased sodium dodecyl sulfate polyacrylamide amide gel electrophoresis mobility of gp160/120 at high concentrations of GPG-NH2. CONCLUSIONS: The tripeptide GPG-NH2 is a nontoxic compound that inhibits the replication of HIV-1 by an apparently new mode of action. PMID- 11213935 TI - Generic substitution: issues for problematic drugs. AB - The methodology and criteria for bioequivalence testing have been firmly established by the Food and Drug Administration (FDA). For certain drugs with a narrow therapeutic index (e.g., digoxin, levothyroxine, warfarin), generic substitution may not be advisable or even allowable, depending on the substitution laws of individual states. Digoxin and levothyroxine tablets are examples of drugs for which no New Drug Applications (NDAs) currently exist. However, commercially available generic products for both of these drugs have not been determined by the FDA to be therapeutically equivalent to the innovator products. Generic versions of warfarin have been approved by the FDA as being therapeutically equivalent to the innovator products, as have generic versions of the rescue inhaler albuterol. Yet, misinformation and myths persist regarding the adequacy and proven reliability of the FDA's determination of bioequivalence for these products. PMID- 11213936 TI - Psoas abscess: a primer for the internist. AB - Psoas abscess is a rare condition with vague clinical presentation. In this article, its epidemiology, etiology, bacteriology, diagnosis, and treatment are discussed. Common diseases that may be erroneously diagnosed in patients with psoas abscess are presented. PMID- 11213937 TI - Information about age-related macular degeneration on the Internet. AB - BACKGROUND: A great deal of health information has become available on the Internet over the past several years. Some of this information is inaccurate or misleading to patients. We attempted to determine the accuracy of information on the Internet concerning age-related macular degeneration (ARMD). METHODS: The term "macular degeneration" was entered in each of seven Internet search engines, and the subsequent links were followed and categorized. The number of sites that discussed treatment inconsistent with the peer-reviewed standard of care for ARMD was tabulated. RESULTS: Of the 80 unique sites regarding ARMD that we identified, 17 (21%) featured nonconventional information. CONCLUSIONS: Many Internet sites feature unproven and costly nonconventional information about ARMD. Each physician should be prepared to address these sites and to suggest reliable sites concerning health information on the Internet. PMID- 11213938 TI - Evolutionary approach to medicine. AB - A new discipline in the medical field, called Darwinian (or evolutionary) Medicine, has arisen to study how natural selection could shape a machine as complex as the human body without eliminating its vulnerability to diseases. It asserts that systems and organs that form our bodies result from millions of years of evolutionary advances and are designed to survive in order to reproduce. According to this principle, Nature does not strive for complexity or perfection it is blind and random. Using the scientific knowledge that has revolutionized biology, Darwinian Medicine seeks to provide an explanation for diseases based on the evolutionary process. This new discipline, in short, can undoubtedly help physicians in their medical practice, though further research is necessary to improve understanding of the range of its clinical application. PMID- 11213939 TI - 'It was the best of times, it was the worst of times...'. PMID- 11213940 TI - Multicenter trial of prolonged infusions of rocuronium bromide in critically ill patients: effects of multiple organ failure. AB - BACKGROUND: This study was done to determine the safety, efficacy, dosing requirements, and spontaneous recovery profiles of prolonged infusions of rocuronium bromide in the critically ill. METHODS: This multicenter, prospective, nonrandomized, open label trial enrolled 32 patients at two university-based medical centers. Patients who were determined to require neuromuscular blockade for at least 24 hours received a bolus of 0.6 mg/kg of rocuronium. After subsequent recovery of two responses (T2) to the TOF stimulation, an infusion of rocuronium was begun at 10 microg/kg/min and continued for 24 to 120 hours as required by the patients' clinical status. RESULTS: Patients were divided into multiple organ failure (MOF) and non-multiple organ failure (non-MOF) groups on enrollment. The mean infusion rates for the MOF and non-MOF groups were 0.2 and 0.5 mg/kg/hour, respectively. CONCLUSION: The mean infusion rate of rocuronium that provides approximately 90% blockade is less for critically ill patients with MOF. Spontaneous recovery was prolonged in patients with MOF. PMID- 11213941 TI - Early experience with laparoscopic antireflux surgery in the rural setting. AB - BACKGROUND: Gastroesophageal reflux (GERD) affects a significant portion of the population, and refractory or untreated disease can have serious long-term complications. Antireflux procedures are now done more frequently because of advances in laparoscopic technique. It has been reported in the literature that the quality of care is better in larger urban hospitals than in smaller facilities. We report our experience with laparoscopic antireflux surgery in a 35 bed rural county hospital. METHODS: We reviewed the charts of 26 patients who had a laparoscopic antireflux procedure in our facility during a 2-year period. Data from the preoperative evaluation, the operative procedure, and the postoperative period were recorded. The patients had office follow-up after the procedure and also were contacted at the time of the study to evaluate their outcome. RESULTS: Ninety-five percent of the patients had excellent symptomatic relief from heartburn and required no medication at follow-up. There was no mortality. Our complication rate was 7%, and the conversion rate to laparotomy was 7%. Most patients were discharged on the day after the procedure. CONCLUSION: Laparoscopic antireflux procedures can effectively relieve symptoms of GERD with minimal morbidity and mortality. The outcome of our initial experience in a small rural facility is analogous to results previously published in the literature. PMID- 11213942 TI - Sexually transmitted diseases during pregnancy: screening, diagnostic, and treatment practices among prenatal care providers in Georgia. AB - BACKGROUND: Sexually transmitted diseases (STD) during pregnancy are associated with adverse outcomes. We conducted a prenatal care provider survey to determine STD screening, diagnosis, and treatment practices. METHODS: Standard questionnaires were mailed to Georgia-licensed obstetrician/ gynecologists, family practitioners, and nurse-midwives (N = 3,082) in 1998. RESULTS: Of the 1,300 care providers who returned the survey, 565 (44%) provided prenatal care, 390 (57%) were male, and 396 (70%) were obstetrician/ gynecologists. Overall, 553 prenatal care providers (98%) reported screening all pregnant patients for syphilis, 551 (98%) for hepatitis B, 501 (89%) for trichomonas, 474 (84%) for human immunodeficiency virus (HIV), 401 (71%) for gonorrhea, 403 (71%) for chlamydia, 475 (84%) for group B streptococci, and 130 (23%) for bacterial vaginosis (BV) (high risk). Less than 10% used amplification tests for chlamydia or gonorrhea. Most providers used appropriate regimens to treat STD in pregnant women. A written office policy on testing for BV or HIV was associated with increased screening. CONCLUSIONS: Provider education is needed about diagnosis and treatment of STD during pregnancy. PMID- 11213943 TI - Ultrasound detection of free intraperitoneal fluid associated with hepatic and splenic injuries. AB - BACKGROUND: The objective of this study was to compare the sensitivity and specificity of 5 abdominal views for detecting free intraperitoneal fluid in trauma patients later diagnosed with hepatic or splenic injuries. METHODS: This retrospective study conducted over a 17-month period enrolled patients with trauma. A Focused Abdominal Sonogram for Trauma (FAST) examination was done using 5 abdominal views. Exploratory laparotomy or computed tomography (CT) confirmed the presence of intraperitoneal fluid and associated injuries. The sensitivity and specificity were determined. RESULTS: Of the 245 study patients, 29 had injuries to the liver or spleen or both. The 5-view FAST examination's sensitivity for detecting free intraperitoneal fluid associated with hepatic, splenic, or combined injuries was 77%, 90%, and 100%, respectively. The sensitivity of the single Morison's pouch view in detecting free intraperitoneal fluid associated with hepatic, splenic, or combined injuries was 38%, 20%, and 67%, respectively. CONCLUSION: For identifying free intraperitoneal fluid associated with hepatic or splenic injuries, no single view of the FAST examination could match the sensitivity provided by the 5-view technique. PMID- 11213944 TI - Vitamin D: balancing cutaneous and systemic considerations. AB - BACKGROUND: Vitamin D insufficiency may lead to various health problems. By encouraging sun protection to prevent skin cancer, physicians may be limiting a major source of vitamin D for many individuals. METHODS: We did a literature review on issues related to vitamin D inadequacy, particularly those relevant to various racial/ethnic groups. RESULTS: Vitamin D is an important hormone with many physiologic roles beyond those related to bones, including blood pressure regulation and acting as a tumor suppressant. The recommended amount of vitamin D has recently increased for adults over age 50. Moreover, some researchers are urging higher doses for the entire population to prevent osteoporotic fractures. CONCLUSIONS: Previous studies that have found serum levels of vitamin D in their sun-protected subjects to be in the normal range may need to be reevaluated. In concert with counseling sun protection, physicians should consider discussing vitamin D intake, typically in the form of supplements. PMID- 11213945 TI - Ventriculitis due to Cryptococcus uniguttulatus. AB - Infections due to non-neoformans cryptococci are rare. We report the first case of a human infection caused by Cryptococcus uniguttulatus. Ventriculitis caused by this organism developed in a 65-year-old woman who had had repair of an internal carotid aneurysm. In vitro sensitivity testing showed the Cryptococcus species sensitive to amphotericin B and itraconazole. Treatment with amphotericin led to resolution of the infection. PMID- 11213946 TI - Influenza A pneumonia with rhabdomyolysis. AB - Influenza A pneumonia accounts for a significant number of the community-acquired pneumonias in the United States. While myalgia is a common complaint in influenza A infection, few cases of rhabdomyolysis associated with this virus have been described. Although it has been recently recognized that rhabdomyolysis complicating certain bacterial pneumonias has important prognostic implications, rhabdomyolysis in the setting of influenza A pneumonia does not appear to carry the same prognostic significance. PMID- 11213947 TI - Chemoprevention of breast cancer. AB - We critically examined the literature regarding tamoxifen and raloxifene for breast cancer chemoprevention, a controversial topic of interest to all providers of health care services for women. The National Surgical Adjuvant Breast and Bowel Project showed that tamoxifen decreased the incidence of breast cancer in women at increased risk. Two European studies did not confirm this benefit. Although well-tolerated, tamoxifen chemoprevention continues to be associated with an increased risk of endometrial cancer. Raloxifene is a promising agent that has not been established to reduce the incidence of breast cancer in women at increased risk and currently should not be considered an alternative to tamoxifen outside of clinical trials. Tamoxifen results in a decreased risk of causing breast cancer in women at increased risk for having the disease. Women at increased risk are encouraged to participate in the ongoing clinical trial comparing tamoxifen and raloxifene for breast cancer prevention. PMID- 11213948 TI - Echolalia as a novel manifestation of neuropsychiatric systemic lupus erythematosus. AB - "That tongue of yours, by which I have been tricked, shall have its power curtailed and enjoy the briefest use of speech." With these words, Hera, of Greek mythology, deprived the nymph Echo of spontaneous speech, constraining her instead to merely repeating the words of others. Echolalia, which derives from the word "echo," is disordered speech in which an individual persistently repeats what is heard. Echolalia has been described in patients with a number of neuropsychiatric illnesses including autism and Tourette's syndrome. Neuropsychiatric systemic lupus erythematosus (NPSLE) is a heterogeneous disease with protean manifestations that may occur in approximately 25% to 50% of patients with systemic lupus erythematosus (SLE). Although the most common manifestations include cognitive dysfunction (50%) and seizures (20%), NPSLE may also present as peripheral neuropathy (15%), psychosis (10%), or other central nervous system abnormalities. We report the case of a 57-year-old woman with SLE and echolalia. PMID- 11213949 TI - Transvaginal ultrasonographic identification of appendicitis in a setting of chronic pelvic pain and endometriosis. AB - Our patient had a history of chronic endometriosis and pelvic pain and complained of recent onset of right-sided abdominal pain, nausea, and vomiting. Transvaginal ultrasonography revealed a thick-walled mass superior and medial to the right ovary, which was thought to be an inflamed appendix. The woman was not pregnant, and the structure appeared to be anatomically separate from the uterus. Subsequent laparoscopy confirmed the diagnosis of acute appendicitis; uncomplicated laparoscopic appendectomy followed. In the setting of chronic endometriosis, other nongynecologic sources of acute pelvic pain must be considered. Surgical intervention is appropriate whenever clinical suspicion for an acute abdomen is high, and the a priori diagnosis of endometriosis should not result in operative delay. PMID- 11213950 TI - Sarcoidosis and opportunistic infections. AB - Two patients receiving steroid therapy for sarcoidosis had a potentially fatal opportunistic infection that was difficult to differentiate from the underlying illness, but was successfully treated after the diagnosis was made. The effects of sarcoidosis on the immune system and the additional effects of steroid therapy on cell-mediated immunity seem to be of real clinical significance, rather than being of theoretical interest alone, because of the risk of infection with intracellular infecting organisms, even if such infections occur relatively infrequently. PMID- 11213951 TI - Pancreatitis due to Ascaris lumbricoides: second occurrence after 2 years. AB - Pancreatitis is a common disease in the United States, with the most likely etiologies being biliary tract disease and alcohol use. Infections with parasites such as Ascaris lumbricoides comprise a small percentage of pancreatitis cases in the United States, but they are a common etiology in developing countries. In the United States, the incidence of pancreatic and biliary ascariasis has been increasing because of the migration of people from endemic countries, as well as increased travel by Americans to such countries. Patients treated for this roundworm can have reinvasion for the same reasons. We report the case of a patient with two episodes of pancreatitis due to A. lumbricoides 2 years apart. PMID- 11213952 TI - Strangulated obturator hernia: still deadly. AB - The case of an elderly, emaciated female patient with recurrent lower abdominal and hip pain associated with nausea and vomiting due to an incarcerated obturator hernia is described. The presence of a Howship-Romberg sign and a tender mass on digital rectal examination in this thin, elderly woman with a small bowel obstruction led to the rapid diagnosis of an obturator hernia by computed tomography (CT). The high mortality rate associated with this most lethal of all abdominal hernias requires a high index of suspicion to facilitate rapid diagnosis and surgical intervention if the survival rate is to be improved. PMID- 11213953 TI - Physicians, firearm counseling, and legal liability. AB - To explore the potential legal consequences to physicians of counseling their patients about gun violence, I consider the question: If a patient divests herself of a firearm upon the advice of her physician and is subsequently the victim of a rape, robbery, aggravated assault, or homicide, could she or her survivors argue convincingly that her physician was negligent? In attempting to answer this question, the four elements that a patient must establish to prevail in a malpractice action against a physician are discussed, and possible strategies for establishing them in the hypothetical case are explored. I conclude that plausible arguments can be made against the hypothetical physician engaged in firearm counseling as described. Conversely, physicians not engaging in discussions of gun safety face substantially lower liability risks. PMID- 11213954 TI - Cerebrospinal fluid shunt infection: a prospective study of risk factors. AB - OBJECT: Hydrocephalus is a common condition of childhood that usually requires insertion of a cerebrospinal fluid (CSF) shunt. Infection is one of the most devastating complications that may arise from the presence of CSF shunts. In this study, the authors prospectively analyzed perioperative risk factors for CSF shunt infection in a cohort of children. METHODS: Between 1996 and 1999, 299 eligible patients underwent CSF shunt operations (insertions and revisions) that were observed by a research nurse at a tertiary care pediatric hospital. Several perioperative variables were recorded. All cases were followed postoperatively for 6 months to note any development of CSF shunt infection. A Cox proportional hazards model was used to analyze the relationship between the variables and the development of shunt infection. Thirty-one patients (10.4%) experienced shunt infection. Three perioperative variables were significantly associated with an increased risk of shunt infection: 1) the presence of a postoperative CSF leak (hazard ratio [HR] 19.16, 95% confidence interval [CI] 6.96-52.91); 2) patient prematurity (< 40 weeks' gestation at the time of shunt surgery: HR 4.72, 95% CI 1.71-13.06), and 3) the number of times the shunt system was inadvertently exposed to breached surgical gloves (HR 1.07, 95% CI 1.02-1.12). CONCLUSIONS: Three variables associated with an increased incidence of shunt infection have been identified. Changes in clinical practice should address these variables, as follows. 1) Great care should be taken intraoperatively to avoid a postoperative CSF leak. 2) Alternatives to placement of a CSF shunt in premature infants should be studied. 3) Surgeons should minimize manual contact with the shunt system and consider the use of double gloves. PMID- 11213955 TI - Predicting shunt failure on the basis of clinical symptoms and signs in children. AB - OBJECT: In evaluating pediatric patients for shunt malfunction, predictive values for symptoms and signs are important in deciding which patients should undergo an imaging study, whereas determining clinical findings that correlate with a low probability of shunt failure could simplify management. METHODS: Data obtained during the recently completed Pediatric Shunt Design Trial (PSDT) were analyzed. Predictive values were calculated for symptoms and signs of shunt failure. To refine predictive capability, a shunt score based on a cluster of signs and symptoms was derived and validated using multivariate methods. Four hundred thirty-one patient encounters after recent shunt insertions were analyzed. For encounters that took place within 5 months after shunt insertion (early encounters), predictive values for symptoms and signs included the following: nausea and vomiting (positive predictive value [PPV] 79%, likelihood ratio [LR] 10.4), irritability (PPV 78%, LR 9.8), decreased level of consciousness (LOC) (PPV 100%), erythema (PPV 100%), and bulging fontanelle (PPV 92%, LR 33.1). Between 9 months and 2 years after shunt insertion (late encounters), only loss of developmental milestones (PPV 83%, LR 36.7) and decreased LOC (PPV 100%) were strongly associated with shunt failure. However, the absence of a symptom or sign still left a 15 to 29% (early encounter group) or 9 to 13% (late encounter group) chance of shunt failure. Using the shunt score developed for early encounters, which sums from 1 to 3 points according to the specific symptoms or signs present, patients with scores of 0, 1, 2, and 3 or greater had shunt failure rates of 4%, 50%, 75%, and 100%, respectively. Using the shunt score derived from late encounters, patients with scores of 0, 1, and 2 or greater had shunt failure rates of 8%, 38%, and 100%, respectively. CONCLUSIONS: In children, certain symptoms and signs that occur during the first several months following shunt insertion are strongly associated with shunt failure; however, the individual absence of these symptoms and signs offers the clinician only a limited ability to rule out a shunt malfunction. Combining them in a weighted scoring system improves the ability to predict shunt failure based on clinical findings. PMID- 11213956 TI - Patient-assessed outcomes after excision of acoustic neuroma: postoperative symptoms and quality of life. AB - OBJECT: The aim of this study was to assess whether outcomes from excision of acoustic neuroma vary among patients and have a material impact on their quality of life (QOL). METHODS: A questionnaire concerning postoperative symptoms and the Short Form 36 (SF-36) QOL instrument were mailed to 97 consecutive patients who had undergone acoustic neuroma surgery via the translabyrinthine approach. The survey response rate was 78% and the symptomatology was consistent with other reports, supporting the representativeness of the sample. The respondents' QOL was rated significantly below published norms and their work capacity was reportedly reduced. Specifically, the following SF-36 dimensions were reduced: physical functioning and role-physical, together with vitality, general health, and social functioning. Greater numbers of postoperative symptoms and larger tumors were associated with a worse rating of physical functioning. More severe balance problems were associated with lower ratings of social functioning. The disparity between the patient's self-estimate and self-measurement and the clinician's assessment of the patient's facial functioning raises doubts about the validity of subjective reports and assessment. CONCLUSIONS: The present study supports the use of generic QOL measures to assess outcome and to draw comparisons between different populations. PMID- 11213957 TI - Cerebrospinal fluid leak after acoustic neuroma surgery: influence of tumor size and surgical approach on incidence and response to treatment. AB - OBJECT: The aims of this study were to review the incidence of cerebrospinal fluid (CSF) leakage complicating the removal of acoustic neuroma and to identify factors that influence its occurrence and treatment. METHODS: Prospective information on consecutive patients who underwent operation for acoustic neuroma was supplemented by a retrospective review of the medical records in which patients with CSF leaks complicating tumor removal were identified. This paper represents a continuation of a previously published series and thus compiles the authors' continuous experience over the last 24 years of practice. In 624 cases of acoustic neuroma the authors observed an overall incidence of 10.7% for CSF leak. The rate of leakage was significantly lower in the last 9 years compared with the first 15, most likely because of the abandonment of the combined translabyrinthine (TL)-middle fossa exposure. There was no difference in the leakage rate between TL and retrosigmoid (RS) approaches, although there were differences in the site of the leak (wound leaks occurred more frequently after a TL and otorrhea after an RS approach, respectively). Tumor size (maximum extracanalicular diameter) had a significant effect on the leakage rate overall and for RS but not for TL procedures. The majority of leaks ceased with nonsurgical treatments (18% with expectant management and 49% with lumbar CSF drainage). However, TL leaks (especially rhinorrhea) required surgical repair significantly more often than RS leaks. This has not been reported previously. CONCLUSIONS: The rate of CSF leakage after TL and RS procedures has remained stable. Factors influencing its occurrence include tumor size but not surgical approach. The TL-related leaks had a significantly higher surgical repair rate than RS-related leaks, an additional factor to consider when choosing an approach. The problem of CSF leakage becomes increasingly important as nonsurgical treatments for acoustic neuroma are developed. PMID- 11213958 TI - Basal ganglia hematomas in severely head injured patients: clinicoradiological analysis of 37 cases. AB - OBJECT: The authors analyzed the clinicoradiological presentation of traumatic basal ganglia hematomas (TBGHs) in severely head injured (SHI) patients. METHODS: The records of 37 patients (28 male and nine female patients with a mean age of 28 years) in whom computerized tomography (CT) scans revealed TBGHs 2 ml or more in volume were retrospectively reviewed. These cases represented 2.4% of the total series of 1526 SHI patients admitted to the authors' institution between 1979 and 1998. Thirty-five patients (94%) were involved in traffic accidents and only two exhibited a period of lucidity. Associated extracranial injuries were seen in 21 patients (57%) and coagulation disorders in 32 (86%). Skull fracture was present in 10 (43%) of the 23 patients in whom skull x-ray films were obtained. Computerized tomography findings indicated diffuse axonal injury in 27 patients (73%), intraventricular hemorrhage in 22 patients (59%), and subarachnoid hemorrhage in 16 patients (43%). In all but two patients, the TBGHs were visible on the initial CT scan, and in 28 cases (76%) these hematomas were contralateral to the side of impact. Hematoma enlargement over the first few posttraumatic days was noted in 65% of the patients in whom control CT scans had been obtained (22 of 34 patients). Four patients (11%) underwent surgery to remove their TBGHs. Final outcomes were poor: 22 patients (59%) died, two (5%) became vegetative, seven (19%) experienced severe disabilities, and only six patients (16%) made a favorable recovery. CONCLUSIONS: Traumatic basal ganglia hematomas are dynamic lesions that tend to enlarge during the acute posttraumatic period. The overall prognosis in this series was poor. Patients in whom the volume of the hematoma was larger than 25 ml and those in whom hematoma volume enlargement or raised intracranial pressure occurred had the worst outcomes, perhaps indicating the need for a more aggressive surgical treatment. PMID- 11213959 TI - High-field magnetic resonance imaging in patients with moyamoya disease. AB - OBJECT: The purpose of this study was to assess the utility of high-field magnetic resonance (MR) imaging as a quantitative tool for estimating cerebral circulation in patients with moyamoya disease. METHODS: Eighteen patients with moyamoya disease who were scheduled to undergo revascularization surgery and 100 healthy volunteers were examined using T2-reversed MR imaging performed using a 3 tesla system. Ten of the 18 patients underwent a second study between 1 year and 3 years after revascularization. Magnetic resonance images obtained in the patients with moyamoya disease were statistically analyzed and compared with those obtained in healthy volunteers. The MR imaging findings were also correlated with results of single-photon emission computerized tomography and conventional cerebral angiography studies. Transverse lines in the white matter (medullary streaks) were observed in almost all persons. In healthy volunteers, the diameter sizes of the medullary streaks increased significantly with age (p < 0.001). Multiple logistic regression analysis revealed that age-adjusted medullary streak diameters were significantly larger in patients with moyamoya disease (p < 0.001). Diameter sizes also increased significantly with the increased severity of cerebral hypoperfusion (p < 0.001) and a higher angiographically determined stage of the disease (p < 0.001). Diameter sizes decreased significantly after surgery (p < 0.001). CONCLUSIONS: The increases in medullary streak diameters observed in patients with moyamoya disease appear to represent vessels dilated due to cerebral hypoperfusion. High-field T2-reversed MR imaging is useful in estimating cerebral circulation in patients with moyamoya disease. PMID- 11213960 TI - Rupture of intracranial aneurysms during treatment with Guglielmi detachable coils: incidence, outcome, and risk factors. AB - OBJECT: The aim of this study was to assess the incidence and outcome of procedure-related rupture of intracranial aneurysms in patients treated with Guglielmi detachable coils (GDCs) and to identify risk factors for this complication. METHODS: Procedure-related rupture occurred in seven of 264 treated aneurysms in 239 consecutive patients. Aneurysm size, history of previous subarachnoid hemorrhage (SAH) caused by the treated aneurysm, timing of treatment after SAH, and the use of a temporary occlusion balloon in the seven procedures in which rupture occurred were compared with the remaining 257 procedures, and these findings were correlated with data from 13 studies in the literature, in which results of 2030 aneurysm treatments were reported. CONCLUSIONS: Procedure related rupture of intracranial aneurysms during GDC treatment occurs in 2.5% of cases and is responsible for 1% of treatment-related deaths. Risk factors are as follows: small aneurysm size, previous SAH, and probably the use of a temporary occlusion balloon. PMID- 11213961 TI - Health-related quality of life after aneurysmal subarachnoid hemorrhage: impacts of bleeding severity, computerized tomography findings, surgery, vasospasm, and neurological grade. AB - OBJECT: Based on the results of earlier studies it is agreed that the significance of aneurysm location and surgery for neuropsychological impairments after subarachnoid hemorrhage (SAH) is secondary to the effects of the bleeding itself. Therefore, the present study was performed to evaluate whether bleeding, acute clinical course, and surgery have persistent effects on health-related quality of life (QOL) after SAH. METHODS: A series of 116 patients was examined for 4 to 5 years (mean 52.2 months) after aneurysmal SAH by means of a QOL questionnaire. Eighty-six patients (74.1%) had undergone surgery early (< or = 72 hours post-SAH). There were 77 women (66.4%) and 39 men (33.6%) in the study group, and the mean age of the patients was 50.3+/-13.3 years (range 30-69 years). Patients who had undergone surgery for a left-sided middle cerebral artery (MCA) aneurysm complained of significantly more impairments in social contact, communication, and cognition than those treated for a right-sided MCA aneurysm. No other effects of aneurysm location (including the anterior communicating artery) emerged. Multiple aneurysms, intraoperative aneurysm rupture, and partial resection of the gyrus rectus had no adverse effects on later daily life. Only temporary clipping was associated with increased complaints in some QOL areas. Disturbances of the circulation of cerebrospinal fluid and the presence of intraventricular hemorrhage led to more impairments in daily life. Specific effects of the anatomical pattern of the bleeding could be identified, but no adverse effects of vasospasm were found. Multivariate analyses revealed, in particular, that patient age and admission neurological status (Hunt and Hess grade) are substantial predictors of the psychosocial sequelae of SAH. CONCLUSIONS: In contrast to the mild effects of aneurysm surgery, patient's age, initial neurological state on admission, and the bleeding pattern substantially influence late QOL after SAH. PMID- 11213962 TI - Increase and uncoupling of adrenomedullin from the natriuretic peptide system in aneurysmal subarachnoid hemorrhage. AB - OBJECT: Natriuresis is a common systemic manifestation of aneurysmal subarachnoid hemorrhage (SAH). Natriuresis and its accompanying hypovolemia may be a major contributing factor in the pathophysiology of symptomatic cerebral vasospasm. METHODS: The authors studied 14 consecutive patients with aneurysmal SAH and compared levels of adrenomedullin (ADM), a novel endogenous natriuretic peptide that possesses additional profound vasodilatory properties, with the natriuretic peptide system by using radioimmunoassay. The mean ADM values on admission were 24.8 pg/ml, a twofold increase over control values, but no correlation was found with atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C natriuretic peptide (CNP) from the natriuretic peptide system. At Day 5 post-SAH, ADM levels were significantly elevated in patients with vasospasm documented angiographically or on transcranial Doppler studies as compared with those who suffered no vasospasm (mean 61.9 pg/ml compared with 15.3 pg/ml, p < 0.01). CONCLUSIONS: The authors conclude that an elevation of ADM in plasma may indicate a physiological regulatory attempt to induce cerebral vasodilation. The regulation of ADM is uncoupled from ANP, BNP, and CNP. PMID- 11213964 TI - Cerebral blood flow alterations in progressive communicating hydrocephalus: transcranial Doppler ultrasonography assessment in an experimental model. AB - OBJECT: In many cases communicating hydrocephalus is the result of impairments in cerebrospinal fluid absorption in the arachnoid villi at the cranial convexity. Reported methods of creating experimental hydrocephalus have not sought to produce an arachnoidal adhesion in the cranial convexity. In this study the authors investigate alterations in cerebral blood flow (CBF) in experimental communicating hydrocephalus induced by the injection of kaolin into the subarachnoid space at the convexity in neonatal rats. METHODS: In neonatal rats, kaolin was injected into the subarachnoid space at the cranial convexity. Assessment of CBF alterations was performed using transcranial Doppler ultrasonography preinjection and at 10 days, 4 weeks, and 8 weeks postinjection. Light microscopy examination was also performed at 4 weeks and 8 weeks postinjection. Conspicuous lateral ventricle enlargements of different dimensions were observed in kaolin-injected rats at 4 to 8 weeks postinjection. The third and fourth ventricles were dilated to a lesser extent. Resistance to CBF and increased mean CBF velocity were apparent 8 weeks after kaolin injection. Further, destruction and even loss of ependymal layers were more prominent at the chronic stage. CONCLUSIONS: The present model may be considered a progressive communicating hydrocephalus because of marked changes in blood flow dynamics and destruction of the ependymal layer at the chronic stage. PMID- 11213963 TI - Transcerebellomedullary fissure approach with special reference to methods of dissecting the fissure. AB - OBJECT: The purpose of the present study was to refine the transcerebellomedullary fissure approach to the fourth ventricle and to clarify the optimal method of dissecting the fissure to obtain an appropriate operative view without splitting the inferior vermis. METHODS: The authors studied the microsurgical anatomy by using formalin-fixed specimens to determine the most appropriate method of dissecting the cerebellomedullary fissure. While dissecting the spaces around the tonsils and making incisions in the ventricle roof, the procedures used to expose each ventricle wall were studied. Based on their findings, the authors adopted the best approach for use in 19 cases of fourth ventricle tumor. The fissure was further separated into two slit spaces on each side: namely the uvulotonsillar and medullotonsillar spaces. The floor of the fissure was composed of the tela choroidea, inferior medullary velum, and lateral recess, which form the ventricle roof. In this approach, the authors first dissected the spaces around the tonsils and then incised the taenia with or without the posterior margin of the lateral recess. These precise dissections allowed for easy retraction of the tonsil(s) and uvula and provided a sufficient view of the ventricle wall such that the deep aqueductal region and the lateral region around the lateral recess could be seen without splitting the vermis. The dissecting method could be divided into three different types, including extensive (aqueduct), lateral wall, and lateral recess, depending on the location of the ventricle wall and the extent of surgical exposure required. CONCLUSIONS: When the fissure is appropriately and completely opened, the approach provides a sufficient operative view without splitting the vermis. Two key principles of this opening method are sufficient dissection of the spaces around the tonsil(s) and an incision of the appropriate portions of the ventricle roof. The taenia(e) with or without the posterior margin of the lateral recess(es) should be incised. PMID- 11213965 TI - Anticonvulsant effects of gamma surgery in a model of chronic spontaneous limbic epilepsy in rats. AB - OBJECT: The management of intractable epilepsy remains a challenge, despite advances in its surgical and nonsurgical treatment. The identification of low risk, low-cost therapeutic strategies that lead to improved outcome is therefore an important ongoing goal of basic and clinical research. Single-dose focal ionizing beam radiation delivered at necrosis-inducing and subnecrotic levels was investigated for its effects on seizure activity by using an established model of chronic recurrent spontaneous limbic seizures in rats. METHODS: A single 90 minute period of repetitive electrical stimulation (inducing stimulus) of the hippocampus in rats elicited a single episode of status epilepticus, followed by a 2- to 4-week seizure-free period. Spontaneous recurrent seizures developed subsequently and persisted for the duration of monitoring (2-10 months). Simultaneous computerized electroencephalography and video recording were used to monitor the animals. After the establishment of spontaneous recurrent seizures, bilateral radiation centered in the ventral hippocampal formation was administered with the Leksell gamma knife, aided by a stereotactic device custom made for small animals. A center dose of 10, 20, or 40 Gy was administered using a 4-mm collimator. Control animals were subjected to the same seizure-inducing stimulus but underwent a sham treatment instead of gamma irradiation. In a second experiment, the authors examined the effects of gamma irradiation on the proclivity of hippocampal neurons to display epileptiform discharges. Naive animals were irradiated with a single 40-Gy dose, as already described. Slices of the hippocampus were prepared from animals killed between 1 and 178 days postirradiation. Sensitivity to penicillin-induced epileptiform spiking was examined in vitro in slices prepared from control and irradiated rat brains. CONCLUSIONS: In the first experiment, single doses of 20 or 40 Gy (but not 10 Gy) reduced substantially, and in some cases eliminated, behaviorally and electrographically recognized seizures. Significant reductions in both the frequency and duration of spontaneous seizures were observed during a follow-up period of up to 10 months postradiation. Histological examination of the targeted region did not reveal signs of necrosis. These findings indicate that single-dose focal ionizing beam irradiation at subnecrotic dosages reduces or eliminates repetitive spontaneous seizures in a rat model of temporal lobe epilepsy. In the second experiment, synaptically driven neuronal firing was shown to be intact in hippocampal neurons subjected to 40-Gy doses. However, the susceptibility to penicillin-induced epileptiform activity was reduced in the brain slices of animals receiving 40-Gy doses, compared with those from control rats that were not irradiated. The results provide rational support for the utility of subnecrotic gamma irradiation as a therapeutic strategy for treating epilepsy. These findings also provide evidence that a functional increase in the seizure threshold of hippocampal neurons contributes to the anticonvulsant influence of subnecrotic gamma irradiation. PMID- 11213966 TI - Augmentation of endothelial function by endothelin antagonism in human saphenous vein conduits. AB - OBJECT: Cerebral revascularization with saphenous vein (SV) conduits is used in the management of hard-to-treat lesions that require deliberate arterial occlusion and in selected patients with occlusive vascular disease. Endothelial dysfunction is thought to contribute to acute perioperative vasospasm and chronic graft atherosclerosis. In the present study the authors examined the contribution of the potent vasoconstrictor endothelin-1 (ET-1) to endothelial dysfunction in human SVs. METHODS: The effects of an ET(A/B) receptor antagonist (bosentan), an ET(A) receptor antagonist (BQ-123), and an ET(B) receptor antagonist (BQ-788) on in vitro endothelium-dependent and -independent responses were studied in human SVs. Vascular segments were obtained in 34 patients who had undergone revascularization procedures, and isometric dose-response curves (DRCs) were constructed using the isolated tissue bath procedure as follows: 1) cumulative DRCs to norepinephrine; and 2) DRCs to acetylcholine (ACh) and sodium nitroprusside in the absence and presence of bosentan, BQ-123, or BQ-788. Maximal vasodilatory responses and sensitivity were compared between groups. In the presence of bosentan (Experiment 1) and BQ-123 or BQ-788 (Experiment 2), ACh responses were significantly augmented (percent maximum relaxation values: 7+/-2 [control] compared with 17+/-3 [bosentan], p < 0.002 [Experiment 1]; and 12+/-2 [control] compared with 29+/-2 [BQ-123] and 25+/-2 [BQ-788], p < 0.003 and p < 0.002, respectively [Experiment 2]). The sensitivity of SVs to ACh was unaffected by treatment. These beneficial effects were specific for the endothelium. CONCLUSIONS: Blockade of ET receptors significantly improves endothelial function in SVs. Furthermore, these effects appear to be independently and maximally mediated by antagonism of either ET(A) or ET(B) receptors. Interventions aimed at improving endothelial function may serve to counter perioperative vasospasm and impede atherosclerosis in SVs used for revascularization procedures. PMID- 11213967 TI - Immunogene therapy with interleukin-2-secreting fibroblasts for intracerebrally metastasizing breast cancer in mice. AB - OBJECT: Breast cancer is the second leading cause of cancer-related death in American women. Brain metastases occur in 15 to 30% of patients with breast cancer, and this usually results in death. Despite the availability of surgery, radiotherapy, and chemotherapy, the prognosis for patients with breast cancer that has metastasized to the intracerebral region remains poor. This study was designed to determine if an intracerebrally metastasizing breast tumor could be treated successfully with a cellular vaccine consisting of allogeneic fibroblasts (H-2K) modified to secrete interleukin (IL)-2. METHODS: The authors used EO771 breast cancer cells, derived from a spontaneously arising breast-cancer tumor in C57BL/6 mice. The authors first determined the length of survival of C57BL/6 mice that had been injected with varying numbers of EO771 cells into the right frontal lobes and found that 100% of those animals that received a dose of 10(4) cells died within 41 days, whereas 100% of the group that received 10(3) cells died within 23 days. Based on these results, 5 x 10(4) EO771 cells were injected into the right frontal lobe of C57BL/6 mice and the animals were treated intracerebrally with a single intratumoral injection of 10(6) allogeneic fibroblasts genetically engineered to secrete IL-2. The allogeneic fibroblasts transfected with the IL-2 gene formed large quantities of IL-2 as measured by an enzyme-linked immunosorbent assay. Control groups of animals were treated with either allogeneic fibroblasts transfected with the retroviral vector, but not the IL-2 gene, or with media. The effects of this treatment on the animal's survival and the tumor's histopathological characteristics were investigated. The results indicate a significant prolongation (p < 0.005) of survival in animals with intracerebrally metastasizing breast cancer treated only with IL-2-secreting allogeneic fibroblasts. Tumor did not develop in four of 10 animals in the IL-2 treated group, and these animals were rechallenged at 90 days by intracerebral injection of tumor, but no treatment cells, and compared with four naive animals receiving intracerebral tumor. Again, animals that previously had been treated with IL-2-secreting fibroblasts had a markedly prolonged survival (p < 0.05) compared with control animals following a second challenge with tumor cells. Histopathological examination revealed smaller tumors associated with lymphocytic infiltrations in the treated animals. CONCLUSIONS: This work represents a new treatment for breast cancer that has metastasized to the brain in which a cellular vaccine consisting of allogeneic fibroblasts genetically engineered to secrete cytokines is used as a novel means for delivery of immunogene therapy and demonstrates the induction of long-term immunity against tumor. PMID- 11213968 TI - Evidence for mitogen-associated protein kinase activation and transduction of mitogenic signals by platelet-derived growth factor in human meningioma cells. AB - OBJECT: Coexpression of platelet-derived growth factor (PDGF)-BB and activated PDGF-beta receptor in meningioma cells indicates that this cytokine may act as an autocrine or paracrine stimulant of meningioma growth. The intracellular events transducing signals from PDGF-beta receptor tyrosine kinases are unknown. In this study the authors evaluated whether or not mitogen-activated protein kinases (MAPKs) are expressed in meningiomas, regulate their growth, and transduce mitogenic signals of PDGF-BB. METHODS: Ten human meningioma tumors as well as cells cultured from two normal leptomeninges and 10 additional human meningiomas were evaluated using Western blot analysis to determine the presence of MAPK and phosphorylated (activated) MAPK. The effects of PD098059, a selective inhibitor of MAPK phosphorylation/activation, on proliferation of meningioma cells stimulated with 10% fetal bovine serum was also evaluated. Last, the authors evaluated whether PDGF-BB stimulation of meningioma cells was associated with activation of MAPK. Western blots of lysates from meningiomas and from cultured leptomeningeal and meningioma cells demonstrated MAPK and phosphorylated MAPK. Treatment with PD098059 produced a 52 to 84% (x = 69.8) loss in [3H]thymidine incorporation, which was associated with a partial or complete loss of phosphorylated MAPK after 3 days of treatment. The PDGF-BB produced a significant increase in [3H]thymidine incorporation and phosphorylation of MAPK at 1 and 3 days. Coadministration of PD098059 completely blocked PDGF-BB's stimulation of [3H]thymidine incorporation and cell proliferation concomitant with reduced MAPK phosphorylation. CONCLUSIONS: The findings indicate that MAPK is constitutively expressed in leptomeningeal and meningioma cells and transduces mitogenic signals of PDGF, contributing to the growth of human meningiomas. PMID- 11213970 TI - Delayed onset of hemidystonia and hemiballismus following head injury: a clinicopathological correlation. Case report. AB - The authors report the case of a young man who suffered multiple injuries in a motor vehicle accident, the most significant of which arose in the brain, creating an unusual clinical syndrome. After experiencing an initial coma for several days, the patient was found to have a right-sided homonymous hemianopsia and a right hemiparesis, which was more marked at the shoulder and was accompanied by preservation of finger movement. Dystonic movements appeared 2 months later and progressed, along with increased spasticity on volition, to severe uncontrolled arm movements at 2 years postinjury. This motor disorder continued to worsen during the following 6 years prior to the patient's death. At autopsy, the left side of the brain was observed to have marked atrophy of the optic tract, a partial lesion of the posterior portion of the medial segment of the globus pallidus (GP), and a reduction in the size of the internal capsule at the level of the GP, suggesting impaired circulation to these areas at the time of injury. The isolated lesion of the internal segment of the GP was the presumed cause of the dystonia, acting through an alteration in thalamic inhibition. The atrophic subthalamic nucleus was the probable cause of the hemiballismus. The authors speculate that this and other delayed and progressive features of this case were the result of an active, but disordered, adaptive process that failed to compensate and, instead, caused even greater problems than the original injury. PMID- 11213969 TI - Establishment and characterization of a novel malignant astrocytoma cell line derived from a tumor removed in a patient with neurofibromatosis type 1. AB - OBJECT: Patients with neurofibromatosis Type 1 (NF1) have a predisposition to development of a variety of benign and malignant tumors including neurofibromas, astrocytomas, pheochromocytomas, and malignant peripheral nerve sheath tumors. The availability of an astrocytoma cell line derived from NF1 would be useful in studies in which sporadic astrocytomas could be compared with NF1-derived astrocytomas. In this article the authors describe a novel astrocytoma cell line, TM-31, that they established from a tumor removed in a 42-year-old woman with NF1. METHODS: The TM-31 cell line was prepared from a surgical specimen of malignant astrocytoma and was serially subcultured over 250 times throughout a 6 year period without showing any sign of cell senescence. Immunocytochemical analyses demonstrated that TM-31 cells are negative for glial fibrillary acidic protein but positive for vimentin and S-100 protein. The TM-31 cells display little neurofibromin expression when subjected to immunoblotting, indicating that there is an NF1 gene mutation. Polymerase chain reaction-single-strand conformational polymorphism analysis revealed that TM-31 cells harbor a p53 point mutation in exon 7, codon 238. Chemosensitivity testing of TM-31 cells revealed a resistance to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3 nitrosourea, although they are sensitive to cisplatin and etoposide. In addition, TM-31 cells displayed no morphological differentiation after all-transretinoic acid and dibutyryl cyclic adenosine monophosphate treatments. Pharmacological inhibition of farnesyltransferase of the Ras oncoprotein led to decreased proliferative activity and inhibition of anchorage-independent growth of TM-31 cells in soft agar. CONCLUSIONS: The TM-31 cell line is an immortalized astrocytoma cell line derived from a tumor obtained in a patient with NF1. Ras activation may be the major event of proliferative activity and of the transformed phenotype of TM-31 cells, and the farnesyltransferase inhibitor may be potentially important as a novel antiproliferative therapy for NF1-derived astrocytomas. PMID- 11213971 TI - Experience with the high occipital transcortical approach in the treatment of intraventricular hemorrhage. Report of two cases. AB - Two patients with intraventricular hemorrhage (IVH) were treated by direct removal of their intraventricular hematomas via a high occipital transcortical approach with successful results. This approach lies between the parietooccipital transcortical approach and the occipital transcortical approach. The patients were a 90-year-old woman with idiopathic IVH and a 60-year-old man with hemorrhage caused by bleeding in the thalamus. In both cases, the hematoma was tightly packed in the lateral ventricle. In the former case, the inferior horn of the lateral ventricle was extremely swollen, and the patient was at risk for development of uncal herniation. With the goals of complete elimination of the hematoma in the inferior horn and identification of the source of bleeding, a high occipital transcortical approach was applied, and the hematoma was removed under direct vision. With the patient in the lateral position, a minor craniotomy of approximately 3 cm was performed around the puncture site of the posterior horn (8 cm craniad from the inion and 3 cm lateral from the midline). A 1-cm cortical incision was made and the posterior horn was reached. First, the portion of hematoma at this site was removed, and then the remainder was completely removed from the interior horn and corpus. Using this method, the entire region of the lateral ventricle, including the inferior horn, corpus, and posterior horn, can be covered in a single operative field, and it is also possible to have sufficient working space for the operation. PMID- 11213972 TI - Cerebral dissection from syringomyelia demonstrated using cine magnetic resonance imaging. Case report. AB - A 16-year-old boy presented at the authors' emergency department with a sudden deterioration of respiration. He had been paraparetic for 3 years and had become quadriplegic 2 days previously. Magnetic resonance images revealed a Chiari I malformation and a hydromyelic cavity extending from C-1 to T-11. Rostrally, a small cylindrically shaped lesion extended from the cervicomedullary junction to the left semioval center. The patient made a dramatic neurological recovery following suboccipital craniectomy and upper cervical laminectomies with augmentation duraplasties followed by placement of a syringoperitoneal shunt. PMID- 11213973 TI - Symptomatic solitary xanthogranuloma occupying the cavernous sinus. Case report. AB - The authors report the first case of a solitary xanthogranuloma of the cavernous sinus without systemic manifestation. A 43-year-old woman experienced decreased visual acuity on the right side in association with papilledema and a visual field defect. She was alert and no other neurological sign was observed. She had no family history of hyperlipoproteinemia and no cutaneous and/or systemic xanthomatous lesions. Skull x-ray films showed an enlarged right superior orbital fissure. Computerized tomography revealed a low-density oval mass 2 x 3 cm in diameter in the right cavernous region that was compressing the right optic nerve in the lateral to medial direction. This mass exhibited isointensity on T1 weighted and mixed-pattern hyperintensity on T2-weighted magnetic resonance images with diffuse contrast enhancement. Cerebral angiography demonstrated fine staining in the margin, originating from the right middle meningeal artery. These neuroimaging findings closely mimicked those associated with trigeminal neuroma. The lesion was partially removed via a right-sided zygomatic approach, and her symptoms improved. Clinical characteristics and histopathological features of this rare case are discussed. PMID- 11213974 TI - Gamma knife surgery for treatment of central neurocytomas. Report of four cases. AB - The authors investigated the use of gamma knife surgery (GKS) in the treatment of central neurocytoma, a usually benign primary brain tumor of the lateral and third ventricles. Four patients with subtotally resected or recurrent central neurocytomas were retrospectively studied. The prescription isodose was 9 to 13 Gy to the 30 to 50% peripheral isodose line. Pre- and postoperative magnetic resonance (MR) images were compared to determine the volume reduction following GKS. Follow-up review included annual MR imaging and clinical evaluation by a neurosurgeon. Follow-up periods ranged from 12 to 99 months. Marked reduction in tumor size was seen in all four patients; the decrease in tumor volume for each was 48%, 72%, 81%, and 77%, respectively, at the last follow-up review. None of the four patients required additional treatment and none experienced a decline in neurological function during the follow-up period. No complications have been noted in any of these patients to date. Even though there have been few observations and follow-up time has been limited, because of the consistency of the response and the lack of observed side effects, GKS may be the treatment of choice for subtotally resected and recurrent central neurocytomas. PMID- 11213975 TI - Giant chondroma arising from the dura mater of the convexity. Case report and review of the literature. AB - Chondromas arising from the dura mater are rare intracranial tumors. The authors present a case of intracranial giant chondroma originating from the dura mater of the convexity. Neuroimaging and surgical findings are described. The diagnostic clues are discussed and similar cases from the literature are reviewed. PMID- 11213976 TI - Secondary abscess formation in pituitary adenoma after tooth extraction. Case report. AB - The presence of an abscess in a pituitary tumor is a very rare finding. The authors report the case of a 69-year-old man with a pituitary adenoma confirmed by neuroimaging results, in whom a high fever, meningismus, and left-sided ophthalmoplegia developed 4 days after tooth extraction. The results of serial cranial magnetic resonance imaging were highly indicative of an abscess formation within the pituitary adenoma. During surgery the tumor was approached transsphenoidally and removed. Histological examination confirmed the presence of an abscess formation within the pituitary adenoma. It is most likely that the tooth extraction caused a bacteremia, which led to an inflammation with abscess formation within the pituitary adenoma. The authors conclude that invasive dental procedures should be avoided before planned resection of a pituitary adenoma. PMID- 11213977 TI - Supracerebellar transtentorial approach to posterior temporomedial structures. AB - The supracerebellar transtentorial (SCTT) approach, a modification of the infratentorial supracerebellar approach, facilitates simple and minimally invasive access to posterior temporomedial structures without requiring retraction of the temporal or occipital lobe. The SCTT approach was used in 16 patients over a 3-year period. Eleven patients harbored tumors confined to, or located mainly within, the posterior hippocampal formation, three patients harbored aneurysms (one ruptured posterior cerebral artery [PCA] aneurysm at the P2-P3 junction, one ruptured giant PCA [P2] aneurysm, and one giant basilar artery-superior cerebellar artery aneurysm), one patient had juvenile-type moyamoya disease, and one patient suffered from medically intractable epilepsy. In these patients, the SCTT approach enabled tumor removal, aneurysm clipping, and vascular bypass procedures. The authors' experience suggests that this approach can be used routinely in treating lesions in the posterior temporomedial region. PMID- 11213978 TI - Astrocytoma cell line. PMID- 11213979 TI - Closing the gender gap. PMID- 11213980 TI - A prospective electromyographic and computer-aided thermal sensitivity assessment of nerve lesions after sagittal split osteotomy and Le Fort I osteotomy. AB - PURPOSE: The purpose of this study was to determine the incidence of temporary and permanent sensory disturbance of the inferior alveolar nerve (IAN) after bilateral sagittal split osteotomy (BSSO) of the mandible and of the infraorbital nerve (ION) after Le Fort I osteotomy, as well as the rate of recovery of sensory function using subjective and objective measures. PATIENTS AND METHODS: Preoperatively and after 1 week, and 1, 3, 6, and 12 months postoperatively, sensibility in the distribution of 36 IONs after Le Fort I osteotomy and 24 IANs after BSSO in 19 patients were investigated by using sharp-blunt testing, 2-point discrimination, electromyographic recording, and thermal sensitivity (Pain and Thermal Sensitivity Test Device [PATH]) tests of the Adelta and C nerve fibers. RESULTS: With conventional clinical sharp-blunt and 2-point discrimination tests, the incidence of temporary impairment was 81% for the ION (29 of 36) and 83% for the IAN (20 of 24). The rate of permanent sensibility disturbance with conventional clinical testing was 6% for the ION and 15% for the IAN. Obvious recovery was found after 1 to 3 months for the ION, but it took 6 to 12 months for the IAN. In contrast, electromyography (EMG) testing showed lower rates of temporary sensory disturbance, namely, 54% (13 of 24) for the ION and 68% (15 of 22) for the IAN. Permanent sensory losses were not found. The results of the EMG test was confirmed by the PATH test. CONCLUSIONS: Objective tests for sensory disturbances show lower rates than the conventional tests. For quality control, preoperative and postoperative measurement and documentation of postoperative recovery of sensation is recommended. PMID- 11213981 TI - Vascularized free fibular flap for mandibular reconstruction: a report of 26 cases. AB - PURPOSE: Mandibular reconstruction represents a challenge to the oral and maxillofacial surgeon and has been revolutionized by the modern microvascular techniques. Rehabilitation using techniques such as reconstruction plates frequently produce a functional and cosmetic defect. The primary objective of the current study was to evaluate the usefulness of the osteomuscular free fibular flap for this purpose. PATIENTS AND METHODS: The results of 26 vascularized free fibula flaps with or without a skin paddle that were used for mandibular reconstruction is presented. The "double barrel" technique was used in 6 cases. The donor site was closed directly in 2 cases and with an abdominal full thickness skin graft in 24 cases. RESULTS: All flaps except 1 were viable. There was partial necrosis of the skin island in 1 patient. The average length of the fibula graft was 10.96 cm, and the number of osteotomies ranged from 0 to 3. In the donor site, the most significant problem was unsatisfactory scarring related to the use of a skin graft. There were no long-term functional complications in the lower leg. Two patients have been secondarily rehabilitated with osseointegrated implants. CONCLUSION: The fibula flap provides a successful bone graft for mandibular restoration with an acceptably low complication rate. This method meets most of the requirements for oral and mandibular replacement. PMID- 11213982 TI - Thermographic imaging of postoperative inflammation modified by anti-inflammatory pretreatment. AB - PURPOSE: The aim of this study was to assess the usefulness of thermography in detecting the postoperative inflammatory reaction after third molar removal. PATIENTS AND METHODS: Thermographic images (NovaTherm; Novamedix Ltd, Hampshire, England) of both cheeks were obtained on the first and seventh postoperative days after removal of impacted mandibular third molars under local anesthesia in 30 patients (15 men, 15 women). The unoperated contralateral side served as a control. One of the following pretreatments was given immediately before the operation: diclofenac (Voltaren; Novartis, Espoo, Finland) 150 mg orally (rapid release 50 mg and prolonged-release 100 mg, n = 15), diclofenac 100 mg orally (prolonged-release) and 50 mg intramuscularly (n = 11), or placebo (n = 4). RESULTS: The postoperative skin surface temperature on the operated side was significantly higher than that on the unoperated side. The thermal difference was 0.9 degrees C +/- 0.1 degrees C on the first postoperative day and declined significantly by the seventh day to 0.3 degrees C +/- 0.1 degrees C (both P < .001). The thermal difference in patients receiving diclofenac preoperatively was significantly smaller (0.8 degrees C +/- 0.1 degrees C at day 1 and 0.2 degrees C +/- 0.1 degrees C at day 7) than in patients receiving placebo (1.6 degrees C +/- 0.1 degrees C at day 1 and 0.8 degrees C +/- 0.3 degrees C at day 7, P < .001). However, with equal doses of diclofenac, the combination of rapid-release and prolonged-release tablets orally was more effective in reducing skin temperature than an orally administered prolonged-release tablet combined with intramuscular injection (P < .001). CONCLUSION: Thermography is a suitable method to measure the inflammatory reaction related to third molar removal. Thermal changes are significant and are decreased by the nonsteroidal anti-inflammatory drug diclofenac. PMID- 11213983 TI - Soft tissue changes of the upper lip associated with maxillary advancement in obstructive sleep apnea patients. AB - PURPOSE: This retrospective study evaluated the horizontal and vertical soft tissue changes that occur with maxillary advancement surgery with a Le Fort I osteotomy with concomitant anatomic reorientation of the nasolabial musculature. SUBJECTS AND METHODS: Fifteen OSA patients who underwent maxillary advancement with a Le Fort I osteotomy without adjunctive nasal soft tissue procedures were studied after a minimum of 8 months of follow-up. The V-Y technique was used to close the maxillary vestibular incision. Only cases with minimal vertical movement (< 3.5 mm) in which no orthodontics were used were included. The average maxillary advancement was 8.0 +/- 2.5 mm, measured at the upper incisor (UPI) and the average vertical movement was 0.7 +/- 1.8 mm. The horizontal and vertical soft tissue change in subnasale (SN), labrale superiorus (LS), superior stomion (SS), nasal tip (NT), nasolabial angle (NLA), and lip length were measured in each patient and correlated with hard tissue measurements at anterior nasal spine (ANS) and UPI. The effect of lip thickness on these soft tissue changes also was evaluated. RESULTS: Using mean data, the horizontal soft-to-hard-tissue ratio for LS to UPI was 0.80:1, with a concomitant vertical (superior) soft tissue change to hard tissue advancement of 0.16:1. Lip length did not change significantly. All patients except 1 showed a slight decrease in nasolabial angle. The average decrease was 5 (range, -10 to +7 ). There was no statistically significant correlation between the degree of change in NLA and the amount of maxillary advancement. CONCLUSION: This study showed that advancement of the maxilla when controlling vertical movement resulted in the a hard-to-soft-tissue ratio of LS:UPI of 0.80:1. NLA did not change significantly. PMID- 11213984 TI - Craniofacial fibrous dysplasia of the fronto-orbital region: a case series and literature review. AB - PURPOSE: Craniofacial fibrous dysplais (CFD), involving the fronto-orbital region often is challenging to treat because of the proximity of neurovascular and ocular structures. This article presents the surgical experience with 6 patients. PATIENTS AND METHODS: Six patients ranging in age from 7 to 23 years, who had undergone surgery for CFD of the orbital region, were retrospectively reviewed. All patients had progressive complaints of deformity, pain, paresthesia or visual disturbances. Surgery generally involved extensive tumor excision and immediate orbital reconstruction with autogenous bone grafts. Two patients also were reconstructed with resected and treated autogenous bone, which then was immediately reimplanted, using rigid fixation. Three patients also had intracranial microsurgical optic canal decompression. All patients received perioperative corticosteroids. RESULTS: Five patients experienced partial relief of their sensory and visual disturbances. These patients also felt that there had been improvement in facial appearance. One patient with very extensive circumferential optic canal involvement, and who underwent 2-wall decompression, suffered visual loss. CONCLUSION: Early surgery to address progressive sensory disturbances is recommended so as to avoid the hazards of late-stage decompression. The risks of surgery must be weighed against the benefits of achieving a more functional and aesthetic result. Long-term neuro-ophthalmologic monitoring is essential. PMID- 11213985 TI - Tissue-engineered mucosa graft for reconstruction of the intraoral lining after freeing of the tongue: a clinical and immunohistologic study. AB - PURPOSE: This article describes the use of tissue-engineered mucosal grafts instead of split-thickness skin grafts after freeing of the tongue in patients who had previous resection of an oral squamous cell carcinoma and initial primary wound closure. PATIENTS AND METHODS: Tissue-engineered mucosal grafts, up to 75 cm2 in size, were cultured from biopsy specimens of the hard palate in 6 patients, starting 3 to 4 weeks before the operation. After freeing of the tongue, the engineered mucosa was implanted on the wound surface by using vaseline gauze as carrier and fixed with an intraoral gauze wound dressing. RESULTS: A good glossoalveolar sulcus was formed in 5 patients, resulting in good mobility of the tongue and a satisfactory denture-bearing surface. In 1 patient, there was a disturbance of wound healing, leading to severe shrinkage of the glossoalveolar sulcus and very limited improvement in tongue mobility. Preoperative bromodeoxyuridine (BrdU) labeling of the graft and postoperative immunohistochemical staining of biopsy specimens from the grafted areas with anti BrdU showed that the cultured cells are integrated into the newly formed mucosal epithelium. Postoperative histologic investigations showed a differentiation process in the grafted mucosal epithelium, with a change in the expression of cytokeratins. At 6 months postoperatively, the typical pattern of normal nongrafted mucosa was regained. CONCLUSIONS: This investigation provides evidence that tissue-engineered mucosal cells can serve as a graft for large intraoral wounds. Complete intraoral lining is quickly reestablished, and normal epithelial differentiation is seen in the graft area within a 6-month postoperative period. PMID- 11213986 TI - The course of the temporal branch of the facial nerve in the periorbital region. AB - PURPOSE: This study identified the terminal temporal and zygomatic branches of the facial nerve as they enter the orbicularis oculi muscle and related these branches to identifiable surface markings. MATERIALS AND METHODS: The temporal and zygomatic branches of the facial nerve were dissected from 5 preserved cadavers (10 sides). The most superior temporal branch entering the orbicularis oculi muscle was identified and related to the lateral canthus of the eye. A vertical line was passed through this point so that the line was equidistant from the nasal tip and chin point. A line perpendicular to the vertical line through the lateral canthus served as the horizontal scale. Vertical and horizontal lines through the lateral canthus were used to establish the anatomic relationship between the lateral canthus and the branch of the temporal nerve entering the orbicularis oculi muscle. RESULTS: The temporal branch was an average of 2.85 +/- 0.69 cm superior to the lateral canthus and an average of 2.54 +/- 0.43 cm lateral to the lateral canthus as it courses into the orbicularis oculi muscle. At the lateral border of the orbicularis oculi muscle, where the temporal and zygomatic nerves insert into the muscle, the mean vertical distance between the temporal and zygomatic nerves was 1.72 +/- 0.62 cm. CONCLUSION: Incisions superior or inferior and parallel to the course of the facial nerve, can provide access to the fronto zygomatic suture and the superior and lateral orbit without damaging its branches. PMID- 11213987 TI - Tissue-engineered composites of bone and cartilage for mandible condylar reconstruction. AB - PURPOSE: This study evaluated the feasibility of creating a tissue-engineered adult human mandible condyle composite of bone and cartilage. MATERIALS AND METHODS: A polymer template composed of polyglycolic acid (PGA) and polylactic acid (PIA), and formed in the shape of the human mandible condyle, was seeded with osteoblasts isolated from a bovine periosteum suspended in calcium alginate. Chondrocytes isolated from the same calf suspended in 30% pluronic were then "painted" onto the articular surface of the scaffold, and it was then implanted into subcutaneous pockets on the dorsum of athymic mice. Animals were divided into 3 groups: group I (n = 6) received a PGA/PLA scaffold saturated with hydrogels not containing cells; group II (n = 6) received scaffolds seeded with both cell types suspended in saline rather than hydrogels; and group III (n = 6) received scaffolds seeded with both cell types suspended in hydrogel composites. Constructs were harvested after 12 weeks and evaluated grossly and microscopically by using histologic stains. RESULTS: In group I, the constructs formed a small mass without evidence of new bone or cartilage. In group II, the constructs were small and irregular. Microscopically they contained scattered islands of bone and cartilage. All specimens in group III retained their original condylar shape and were quite firm. Microscopic evaluation indicated trabecular bone interfacing with hyaline cartilage on the articulating surface. CONCLUSION: These findings show that the composites of bone and cartilage can be engineered to serve as condylar substitutes. The interdigitation of bone and cartilage at their interface is similar to the normal interface of these composite tissues seen in articulating joints. PMID- 11213988 TI - Preliminary investigation of the biomechanics of internal fixation of sagittal split osteotomies with miniplates using a newly designed in vitro testing model. AB - PURPOSE: This article reports a preliminary study undertaken to investigate the biomechanics of internal fixation systems for sagittal split ramus osteotomy of the mandible with advancement, using a newly designed 3-point bovine rib testing model. MATERIALS AND METHODS: After 1 of 5 different miniplates internal fixation systems was placed, a vertical load was applied just below the superior border of sagittal split osteotomy gaps in bovine ribs positioned in a custom-made cradle using a compound cantilered bar device. Load/displacement data were gathered, and the mean elastic limits of the 5 miniplate designs were compared by using a 1-way analysis of variance (ANOVA) with Tukey multiple comparisons. RESULTS: The elastic limit of the rigid fixation system was higher when using a curved plate design than with a straight plate design. CONCLUSION: The 3-point bovine rib model used in this study is an inexpensive, discriminating, and reproducible method for testing internal fixation systems on sagittal ramus osteotomies under conditions that more accurately represent the human mandible in function. PMID- 11213989 TI - Maxillary sinusitis after augmentation of the maxillary sinus floor: a report of 2 cases. PMID- 11213990 TI - An unusual postextraction hemorrhage associated with Klippel-Trenaunay-Weber syndrome. PMID- 11213991 TI - Intramuscular hemangioma of the temporalis muscle. PMID- 11213992 TI - Gastric mucosal choristoma of the tongue and floor of the mouth. PMID- 11213993 TI - Interface analysis of titanium implants in a human vascularized fibula bone graft. PMID- 11213994 TI - Treatment of obstructive sleep apnea syndrome by mandibular elongation using osseous distraction followed by a Le Fort I advancement osteotomy: case report. PMID- 11213995 TI - Treatment of mandibular malignant fibrous histiocytoma during pregnancy. PMID- 11213996 TI - Ganglion of the temporomandibular joint: case report. PMID- 11213998 TI - Castleman disease (giant lymph node hyperplasia) in the maxillofacial region: a report of 3 cases. PMID- 11213999 TI - Solitary intraosseous neurofibroma of the inferior alveolar nerve: report of a case. PMID- 11214000 TI - Use of bone rongeur to aid in splitting the ascending ramus during mandibular sagittal split ramus osteotomy. PMID- 11214001 TI - A modified mandibular ramus osteotomy for orthognathic surgery. PMID- 11214002 TI - "Insuring" against allegations of discrimination. PMID- 11214003 TI - Management of the paranasal sinus mucocele. PMID- 11214004 TI - The heart of the matter--new insights into the genetics of cardiomyopathy. PMID- 11214005 TI - S100-B in blood: a marker of brain damage or simply a covariate? PMID- 11214006 TI - Neurologic injury in cardiac surgery: aortic atherosclerosis emerges as the single most important risk factor. AB - With older and sicker patients undergoing cardiac surgery, neurologic injury has emerged as an increasingly important cause of rising costs, morbidity and mortality. Several studies investigating the relationship between atherosclerotic aortic disease and subsequent adverse clinical outcomes have demonstrated that the single most important risk factor for neurologic injury following cardiac surgery is the presence of aortic atheromatous disease. The results of these studies suggest that atheroemboli are correlated with neurologic injury following cardiac surgery. Surgical techniques to avoid and prevent particulate debris during cardiac surgery may be a major step in preventing severe neurologic injury. PMID- 11214007 TI - A novel missense mutation, Leu390Val, in the cardiac beta-myosin heavy chain associated with pronounced septal hypertrophy in two families with hypertrophic cardiomyopathy. AB - OBJECTIVE: An examination of the genetic background and phenotypic presentation of familial hypertrophic cardiomyopathy (FHC) with respect to specific mutations in the MYH7-gene encoding the cardiac beta-myosin heavy chain. SETTINGS: Two families (n = 22) from a cohort of 67 families with FHC were studied at the National University Hospital, Rigshospitalet, Copenhagen. METHODS: Clinical, non invasive examinations of all included family members followed by molecular genetic analysis including PCR-single strand conformation polymorphism/heteroduplex (SSCP/HD) analysis and sequencing of exon 3-23 of the MYH7-gene. RESULTS: We found FHC associated with a missense mutation in two families, i.e. a C > G transversion at position g10124 and a G > T transversion at position g10126 causing the change of a leucine residue at codon 390 to a valine residue. The mutation is located in the actin-binding region of the beta myosin heavy chain. The leucine residue is evolutionarily conserved in vertebrate myosins. In the two families, the phenotypic presentations in the clinically affected were characterized by asymmetric septal hypertrophy (septum diameter 18.8 (5.0) mm (mean (SD)) with only minor involvement of the left ventricular free wall (posterior wall diameter 11.0 (2.2) mm). Furthermore, the left ventricular systolic and diastolic functions were well preserved, even at a high age. The symptomatic status of the clinically affected patients depended on the presence or absence of a concomitant left ventricular outflow tract gradient. CONCLUSIONS: We report a novel missense mutation associated with FHC caused by a double nucleotide transversion. The penetrance of the mutation was not complete, but in clinically affected patients the mutation gives rise to an echocardiographic phenotype, predominantly characterized by pronounced septal hypertrophy. PMID- 11214008 TI - Outcome of septal myectomy in patients with hypertrophic obstructive cardiomyopathy. AB - OBJECTIVES: To study the outcome of septal myectomy in patients with hypertrophic obstructive cardiomyopathy. DESIGN: Septal myectomy in patients with hypertrophic cardiomyopathy with obstruction of the left ventricular outflow tract (HOCM) is symptomatically effective, and complication rates have been found to be low in large centres performing the procedure routinely. Representing a small centre we studied the outcome after septal myectomy in 11 consecutive patients, aged 44 +/- 21 (mean +/- SD) years with HOCM myectomized at our institution from 1991 to 1998. The patients were evaluated preoperatively using echocardiography and left sided heart catheterization. RESULTS: Eight patients were operated on after medical treatment had failed and three after sudden deterioration of cardiac function. A Morrow myectomy was performed in 10 patients and a modified Konno procedure in one. Significant reductions were observed in left ventricular outflow tract gradients (77 +/- 29 to 10 +/- 7 mmHg, p < 0.01; n = 11), the degree of mitral valve regurgitation (grades 0-3) (1.7 +/- 1.0 to 0.8 +/- 0.7, p < 0.01; n = 11), NYHA functional classification score (2.4 +/- 1.0 to 1.5 +/- 0.7, p < 0.01; n = 11) and all five patients with angina preoperatively had an improved CCS angina classification score. There were no operative or early postoperative (30 days) deaths. One patient operated on with the modified Konno procedure was reoperated for a septal patch suture leak. During follow-up (43 +/- 24 months, range 11-83), the linearized mortality rate was 3.6% per year. One patient died from a pancreas cancer, one probably from coronary artery disease and one suddenly of unknown cause. CONCLUSION: We conclude that septal myectomy efficiently relieves symptoms in HOCM patients, possibly reflecting the direct as well as secondary effects of left ventricular outflow tract gradient reduction. The present results, obtained at a smaller centre for this procedure, should be considered when choosing from available therapeutic alternatives when medical therapy fails: dual chamber pacemaker implantation, percutaneous transluminal septal myocardial ablation or myectomy. PMID- 11214009 TI - Serum S-100beta protein predicts brain injury after hypothermic circulatory arrest in pigs. AB - OBJECTIVE: Serum S-100beta protein is suggested to be a neurobiochemical marker of brain injury after cardiac and aortic arch surgery. The aim of the present study was to investigate the predictive value of S-100beta protein with respect to histopathological analysis of the brain after a prolonged period of hypothermic circulatory arrest (HCA). METHODS: Eighteen pigs (21 to 31 kg) underwent a 75 min period of HCA at 20 degrees C. Serum concentrations of S 100beta were assayed in mixed venous blood before and 2, 4, 7 and 20 h after HCA. A semiquantitative post-mortem histopathological analysis scoring all main regions of the brain was carried out in every animal. RESULTS: All animals were stable during and after cardiopulmonary bypass (CPB) and survived at least to the first postoperative day. Ten of the 18 animals survived 7 days after surgery and were electively sacrificed. Animals with severe histopathological injury showed higher serum S-100beta protein levels at every time point after HCA. The strongest correlation between the total histopathologic score and serum S-100beta levels was found at 7 h after HCA (tau = 0.422 and p = 0.023). CONCLUSION: Serum S-100beta protein levels correlate with histopathological injury after a prolonged period of HCA in pigs. This finding supports the results of previous studies suggesting the potential accuracy of S-100beta in the prediction of brain injury after cardiac surgery. PMID- 11214010 TI - Bundle branch block and acute myocardial infarction. Treatment and outcome. AB - OBJECTIVE: To study early diagnosis, treatment and outcome in patients with bundle branch block and clinically suspected acute myocardial infarction. DESIGN: A prospective multicenter study including 14 Swedish coronary care units. The study included 257 consecutive patients with bundle branch block and clinical suspicion of acute myocardial infarction. RESULTS: Left bundle branch block was present in 62% of patients and right bundle branch block in 38%. Thrombolytic treatment of acute myocardial infarction in the left and right bundle branch block was 16% and 36%, respectively. Of those undergoing thrombolytic therapy, 20% of patients with left and 13% with right bundle branch block did not develop an acute myocardial infarction. Patients with left bundle branch block had higher mortality rates than those with right bundle branch block. After one year there was no difference in mortality rates between patients with and those without acute myocardial infarction on admission. CONCLUSION: Patients with bundle branch block and suspected acute myocardial infarction receive suboptimal treatment. Thus better diagnostic regimes are needed to identify those patients with bundle branch block and acute myocardial infarction who are suitable for thrombolytic treatment. PMID- 11214011 TI - Depression after coronary heart disease events. AB - OBJECTIVE: To study the prevalence of depression at least 6 months after various coronary heart disease (CHD) events (bypass grafting, coronary angioplasty, myocardial infarction, myocardial ischaemia without infarction) and the associations between depression and clinical variables. DESIGN: In the course of the study 414 (284 males, 130 females) patients younger than 71 years (mean age for men 60.9 years and for women 63.6 years) were interviewed and examined. Smoking habits, body mass index, lipid levels and diabetic status were recorded. The New York Heart Association (NYHA) class was assessed. Depression was screened using a self-rated depression scale. RESULTS: In the four diagnostic categories, one-sixth of the patients (14-19%) suffered from depression. Depression was associated with smoking (OR 1.7, 95% CI 1.2; 2.4) and poor NYHA class (OR 1.9, 95% CI 1.4; 2.6). CONCLUSION: Depression is common after CHD events, and is associated with smoking and poor NYHA class. The identification and treatment of depression should be one of the elements in the rehabilitation of cardiac patients. PMID- 11214012 TI - Inverse association between birth weight, birth length and serum total cholesterol in adulthood. AB - OBJECTIVES: To investigate whether impaired fetal growth, measured by low birth weight and short birth length, is linked with raised levels of serum lipids and increased risk and mortality of coronary heart disease. DESIGN: The association between birth length, birth weight, Ponderal Index and total serum cholesterol was examined in 545 Danish men and women aged 31 to 51 years who participated in the Ebeltoft Health Promotion Project in Denmark. RESULTS: No associations were found in women. For men, a negative association was found between birth weight and serum total cholesterol, with a fall in mean serum total cholesterol from 6.03 mmol/l at birth weight below 3300 g to 5.64 mmol/l at birth weight above 4000. A similar association was found between birth length and serum cholesterol, with a mean value of 6.23 mmol/l at birth length below 51 cm and a mean value of 5.56 mmol/l at birth length above 54 cm. No associations were found for Ponderal Index. Between 3% and 8% of the variance in serum total cholesterol could be explained by the statistical models used in this study. CONCLUSION: Our findings support the hypothesis of a negative association between birth weight, birth length and elevated serum cholesterol in adult life, but only in men. PMID- 11214013 TI - Influence of glutaraldehyde fixation on the detection of SLA-I and II antigens and calcification tendency in porcine cardiac tissue. AB - OBJECTIVE: Immunological effects have been addressed as key factors for the long term results of biological porcine aortic prostheses. In this study we investigated the influence of glutaraldehyde fixation on the expression of SLA (swine leucocyte antigens) and the calcification of porcine cardiac tissue. DESIGN: Deparaffinized sections obtained from porcine aortic tissue were fixed in a buffered glutaraldehyde solution for 1, 2, 3, 24 and 72 hours, respectively, and finally immunostained with monoclonal anti-SLA class I antibody 2.27-3a and anti-SLA-II antibody MSA3. Sixteen samples from fixed porcine cardiac tissue and, for comparison, 8 samples from leaflets of Toronto-SPV and Freestyle valves were implanted subcutaneously in 10 Wistar rats for 12 weeks and their calcium content was measured by atomic absorption spectrophotometry. RESULTS: SLA-I epitopes were no longer detectable using anti-SLA-I antibodies after fixation for 3 h. The SLA II antigens remained detectable after longer fixation period. Short-time fixation resulted in marked calcification of the porcine cardiac tissue and to destruction of the SLA-I epitopes, whereas, even after longer fixation time, the epitopes of the SLA-II antigen remain unaffected. CONCLUSION: Chelate formation due to glutaraldehyde treatment provides protection against calcification. Short-time fixed porcine cardiac tissue has a tendency towards a greater degree of calcification than longer fixation periods. Based on the present results, it is pointless to set the length of fixation to switch off the immunogenicity. PMID- 11214014 TI - Effect of allopurinol on myocardial oxygen free radical production in coronary bypass surgery. AB - OBJECTIVES: Allopurinol protects the heart from reperfusion injury. The aim of this study was to investigate myocardial free radical production during reperfusion with and without allopurinol treatment in coronary artery bypass grafting patients randomized into allopurinol (n = 14) or placebo (n = 13) groups. DESIGN: Allopurinol (1 g) was given blind prior to cardiopulmonary bypass and prior to opening the aorta. Oxygen free radicals were measured before anesthesia in arterial blood, before cross-clamping and 1 and 10 min after reperfusion in arterial and coronary sinus blood. Levels were measured as relative concentrations by the electron spin resonance method. RESULTS: One minute after reperfusion the level of spin-trapped radicals in arterial blood was elevated significantly (p = 0.016) in the allopurinol group, from 7.7 (SE: 0.8) to 8.6 (1.4) and non-significantly (p = 0.074) in the placebo group, from 7.3 (0.7) to 8.3 (0.8). Ten minutes after reperfusion the arterial values were 8.6 (1.5) in the allopurinol and 7.6 (0.7) in the placebo group, the sinus values being 7.6 (1.3) and 8.3 (0.8), respectively. Myocardial free radical production was -0.94 (1.21) in the allopurinol and +0.79 (0.96) in the placebo group after 10 min reperfusion, the difference being significant (p = 0.043). CONCLUSIONS: All patients in both groups had an increasing tendency to free radical production during early reperfusion. Patients treated with allopurinol showed less myocardial production of free radicals, indicating that its protective effect may be due to its antioxidative properties. PMID- 11214015 TI - Middle cerebral artery circulation during carotid surgery. A transcranial Doppler study. AB - OBJECTIVE: Perioperative carotid cross-clamping might induce low stump pressures as well as hypoperfusion of the middle cerebral artery. In this study blood flow velocities in the middle cerebral artery were compared with intraoperative measurements of the poststenotic carotid blood pressure. DESIGN: Forty-one patients with internal carotid artery stenosis were operated on without shunting, under general anesthesia. Poststenotic carotid pressures and middle cerebral artery flow velocities were measured before and during cross-clamping. The hemodynamic responses to preoperative carotid compressions and intraoperative cross-clamping were evaluated. RESULTS: In seven patients the poststenotic carotid blood pressure decreased on clamping despite unchanged or even increased middle cerebral artery blood flow velocities. In all other patients, pressure changes were significantly correlated to the decrease in middle cerebral artery blood flow velocities. Autoregulatory blood flow velocity responses after preoperative common carotid artery compression were not reproducible by cross clamping. CONCLUSIONS: Stump blood pressure measurements may not reflect middle cerebral artery perfusion in about 20% of thrombendarterectomies performed under general anesthesia. A possible explanation might be dimished cerebral autoregulation and changes in collateral flow distributions. PMID- 11214016 TI - Aggressive surgical treatment of multiple primary lung cancers. AB - A case of triple primary lung cancers--squamous cell carcinoma, adenocarcinoma and large-cell carcinoma--is presented. Surgical treatment comprised, respectively, left pneumonectomy, partial resection of the right upper lobe and completion right upper lobectomy. The postoperative courses were uneventful and the patient remains well, with no sign of recurrence, 20 months after the third operation. PMID- 11214017 TI - Primary lymphoma of the heart. AB - Primary tumors of the heart are rare. Most patients have very few clinical manifestations and present with uncharacteristic symptoms, often misdiagnosed as heart failure. As investigation techniques such as echocardiography, computed tomography and magnetic resonance imaging become more widespread, the clinician will be confronted with the diagnosing of cardiac masses. Early identification is essential for optimum treatment. We present a case of malignant lymphoma of the heart, where treatment led to remission from cardiac growth of the tumor. PMID- 11214018 TI - Implications and refinements of the establishing operation concept. AB - In this paper I discuss (a) three steps in the development of establishing operation (EO) terminology, (b) my early neglect of its possible relevance to applied behavior analysis, (c) the importance of functional analysis methodology for increasing awareness of EO issues, and (d) three comprehensive reviews that clarify the role of EOs in applied work. I then review and further analyze seven topics that require further clarification or that have been raised since my 1982 and 1993 articles: the EO evocative effect, deprivation and satiation, problem behavior maintained by attention, decreasing behavior evoked by a transitive conditioned establishing operation, EOs in the context of escape and avoidance, academic demand, and decreasing behavior evoked by a reflexive conditioned establishing operation. PMID- 11214019 TI - Current research on the influence of establishing operations on behavior in applied settings. AB - This article provides commentary on research published in the special section of the Journal of Applied Behavior Analysis devoted to establishing operations (EOs). Three major themes are highlighted: (a) identification of the influence of EOs on behavior in applied settings, (b) the use of EO manipulation as an assessment tool, and (c) the development of interventions based on the alteration of EO influences. Methodological issues pertaining to research on EOs are addressed, and suggestions for future investigation are provided. PMID- 11214020 TI - A method for identifying satiation versus extinction effects under noncontingent reinforcement schedules. AB - We evaluated one method for determining whether response suppression under noncontingent reinforcement (NCR) is a function of satiation or extinction. Three individuals with developmental disabilities who engaged in self-injurious behavior (SIB) or aggression participated. Results of functional analyses indicated that their problem behavior was maintained by social-positive reinforcement. NCR procedures, individualized for each participant, were implemented in a multiple baseline across subjects design and were associated with decreases in all participants' problem behavior. Identification of the mechanism by which NCR produced these effects was based on examination of cumulative records showing response patterns during and immediately following each NCR session. Satiation during NCR should lead to a temporary increase in responding during the post-NCR (extinction) period due to a transition from the availability to the unavailability of reinforcement (satiation to deprivation). Alternatively, extinction during NCR should reveal no increase in responding during the extinction period because the contingency for the problem behavior would remain unchanged and the transition from satiation to deprivation conditions would be irrelevant. Results suggested that the operative mechanisms of NCR were idiosyncratic across the 3 participants and appeared to change during treatment for 1 of the participants. PMID- 11214021 TI - Effects of noncontingent reinforcement on problem behavior and stimulus engagement: the role of satiation, extinction, and alternative reinforcement. AB - This study examined the effects of noncontingent reinforcement (NCR) with and without extinction on problem behavior and stimulus engagement (consumption of reinforcement) of 4 participants. Reductions in problem behavior using NCR have frequently been attributed to both satiation of the reinforcer and extinction. In the current study, aspects of the NCR treatment effects were difficult to explain based solely on either a satiation or an extinction account. Specifically, it was found that stimulus engagement remained high throughout the NCR treatment analysis, and that problem behavior was reduced to near-zero levels during NCR without extinction. The implications of these findings are discussed with respect to the satiation and extinction hypotheses frequently described in the applied literature. Findings from basic studies examining the effects of response independent schedules are presented, and are used as the basis for a matching theory account of NCR-related effects. It is proposed that reductions in problem behavior observed during NCR interventions may be a function of the availability of alternative sources of reinforcement. PMID- 11214022 TI - Relative influences of establishing operations and reinforcement contingencies on self-injurious behavior during functional analyses. AB - In the typical functional analysis in which the antecedent and consequent events associated with problem behavior are manipulated, the control condition involves elimination of both the relevant establishing operation (EO) and its associated contingency through a schedule of noncontingent reinforcement (usually fixed-time [FT] 30 s). In some functional analyses, however, antecedent events are manipulated in the absence of differential consequences, and a common test condition in such analyses also involves the delivery of reinforcement on an FT 30-s schedule. Thus, the same schedule of reinforcement (FT 30 s) is not considered to be an EO in the former type of analysis but is considered to be an EO in the latter. We examined the relative influences of EOs and reinforcement contingencies on problem behavior by exposing 6 individuals who engaged in self injurious behavior (SIB) to four combinations of functional analysis conditions: EO present/contingency present, EO absent/contingency present, EO present/contingency absent, and EO absent/contingency absent. Results indicated that the only condition in which high rates of SIB were observed consistently was one in which the EO and the reinforcement contingency were both present. Implications of these results for the design of functional analysis test and control conditions are discussed. PMID- 11214024 TI - Escape behavior during academic tasks: a preliminary analysis of idiosyncratic establishing operations. AB - The presence or absence of idiosyncratic stimuli has been demonstrated to predictably alter the occurrence of problem behavior. By specifying stimuli related to negatively reinforced behavior during academic tasks, it may be possible to identify methods of instruction that decrease the occurrence of problem behavior. The current study used a four-step procedure that involved a functional analysis, descriptive assessment, establishing operations (EO) analysis, and follow-up evaluation (a) to identify the operant function of destructive behavior and (b) to evaluate the effects of idiosyncratic features of academic task demands and related methods of instruction on the occurrence of negatively reinforced destructive behavior of 3 boys with developmental disabilities and autism in a classroom setting. The data suggest that the four step procedure was effective in identifying methods of instruction that decreased the likelihood of destructive behavior without disrupting the maintaining contingencies for destructive behavior. Results are discussed in terms of establishing operations for negatively reinforced destructive behavior during academic tasks and related methods of instruction in classroom settings. PMID- 11214023 TI - The effects of presession exposure to attention on the results of assessments of attention as a reinforcer. AB - The effects of presession exposure to attention on responding during subsequent assessments of attention as a reinforcer were evaluated across three behavioral assessments. In Experiment 1, a contingent attention assessment condition was preceded by either a noncontingent attention condition (free play) or a contingent escape condition. In Experiment 2, a diverted attention with extinction condition was preceded by either an alone or a free-play condition. In Experiment 3, a two-choice preference assessment was preceded by either 10 min of free play or 10 min of playing alone. In each experiment, the participant responded differentially within the test condition according to the presence or absence of dense schedules of attention immediately prior to that condition. The results of this study show that events occurring immediately prior to an assessment condition can influence behavior within the assessment. PMID- 11214025 TI - Effects of deprivation on engagement in preferred activities by persons with developmental disabilities. AB - This study examined the effects of deprivation on engagement in activities for 3 adult men with developmental disabilities. First, an assessment was conducted to identify a high- and a low-preference activity for each participant. Second, the high-preference activity was made available following three amounts of deprivation of the activity (15 min, 2 hr, and 1 to 4 days); the low-preference activity was made available following the schedule of deprivation that produced the highest level of engagement by each participant in the high-preference activity. The results were that 1 to 4 days of deprivation produced the highest average amounts of engagement in the high-preference activity for each participant; this amount of deprivation did not produce high engagement in the low-preference activities. Third, the deprivation procedures and results were replicated when high-preference activities were presented by teachers during the participants' daily activities when their engagement had been quite low. PMID- 11214026 TI - "Transitional objects" as establishing operations for thumb sucking: a case study. AB - This study examines the effects of a "transitional object" (surgical cloth) on the thumb sucking of a 3-year-old boy in two conditions: while sitting in the lap of his physical therapist and while alone in his crib. Sucking occurred when the cloth was present and did not occur when it was absent, regardless of condition. These results are discussed in terms of establishing operations, object attachment, and application. PMID- 11214027 TI - Assessment of the influence of background noise on escape-maintained problem behavior and pain behavior in a child with Williams syndrome. AB - We examined the influence of background noise on levels of problem behavior and pain behavior under functional analysis conditions for a child with a diagnosis of Williams syndrome and hyperacusis. Background noise was associated with increases in escape-maintained problem behavior and increases in pain behavior such as clasping ears and crying. When the child was fitted with earplugs, there were substantial reductions in both problem and pain behavior under the background noise condition. PMID- 11214028 TI - Recombinative generalization of within-syllable units in prereading children. AB - This study demonstrates recombinative generalization of within-syllable units in prereading children. Three kindergarten children learned to select printed consonant-vowel-consonant words upon hearing the corresponding spoken words. The words were taught in sets; there were six sets, presented consecutively. Within sets, the four words that were taught had overlapping letters, for example, sat, mat, sop, and sug. Tests for recombinative generalization determined whether the children selected novel words with the same components as the trained words (e.g., mop and mug). Two children demonstrated recombinative generalization after one training set, and the 3rd demonstrated it after two training sets. In contrast, 2 other children, who received tests but no training, showed low accuracy across six sets. The 3 experimental children then demonstrated highly accurate printed-word-to-picture matching, and named the majority of the printed words. These findings are a promising step in the development of a computerized instructional technology for reading. PMID- 11214029 TI - Preference for unreliable reinforcement in children with mental retardation: the role of conditioned reinforcement. AB - We examined the effects of conditioned reinforcement on children's choice between reliable (100%) and unreliable (50%) reinforcement under various stimulus conditions in a concurrent-chains procedure. The study was conducted across three experiments. Experiments 1 and 2 were conducted under conditions similar to basic laboratory work and consisted of participants selecting from one of two black boxes (placed on a table) that were correlated with different reinforcement schedules. In Experiment 3, we assessed a participant's preference for unreliable reinforcement during conditions in which the target responses were aggression and mands. Results of the three experiments showed that the participants preferred unreliable reinforcement under certain conditions. Findings are discussed regarding the role of specific stimuli (i.e., items correlated with a reinforcement schedule, adult reactions) as conditioned reinforcers and how they may influence children's preference for a response (e.g., aggression, self injury) that produces reinforcement on a leaner schedule than a socially desirable response (e.g., mands). PMID- 11214030 TI - Variable-time reinforcement schedules in the treatment of socially maintained problem behavior. AB - Noncontingent reinforcement (NCR) consists of delivering a reinforcer on a time based schedule, independent of responding. Studies evaluating the effectiveness of NCR as treatment for problem behavior have used fixed-time (FT) schedules of reinforcement. In this study, the efficacy of NCR with variable-time (VT) schedules was evaluated by comparing the effects of VT and FT reinforcement schedules with 2 individuals who engaged in problem behavior maintained by positive reinforcement. Both FT and VT schedules were effective in reducing problem behavior. These findings suggest that VT schedules can be used to treat problem behavior maintained by social consequences. PMID- 11214031 TI - Analyzing the multiple functions of stereotypical behavior for students with autism: implications for assessment and treatment. AB - We studied behavioral functions associated with stereotypical responses for students with autism. In Study 1, analogue functional analyses (attention, demand, no-attention, and recreation conditions) were conducted for 5 students. Results suggested that stereotypy was multiply determined or occurred across all assessment conditions. For 2 students, stereotypy was associated with positive and negative reinforcement and the absence of environmental stimulation. For 2 other students, stereotypy occurred at high levels across all experimental conditions. For the 5th student, stereotypy was associated with negative reinforcement and the absence of environmental stimulation. In Study 2, the stereotypy of 1 student was further analyzed on a function-by-function basis. Within a concurrent-schedules procedure, alternative responses were taught to the student using functional communication training. The results of Study 2 showed that similar topographies of stereotypy, based on qualitatively different reinforcers, were reduced only when differential reinforcement contingencies for alternative forms of communication were implemented for specific response reinforcer relations. Our results suggest that the causes of stereotypy for students with autism are complex and that the presumed association between response topography and behavioral function may be less important than previously realized. PMID- 11214032 TI - Effects of methylphenidate on sensitivity to reinforcement in children diagnosed with attention deficit hyperactivity disorder: an application of the matching law. AB - The behavior of children diagnosed with attention deficit hyperactivity disorder (ADHD) has been hypothesized to be the result of decreased sensitivity to consequences compared to typical children. The present study examined sensitivity to reinforcement in 2 boys diagnosed with ADHD using the matching law to provide more precise and quantitative measurement of this construct. This experiment also evaluated the effects of methylphenidate (MPH) on sensitivity to reinforcement of children with ADHD. Subjects completed math problems to earn tokens under four different variable-interval (VI) schedules of reinforcement presented in random order under both medicated and nonmedicated conditions. Results showed that, in the medicated condition, the matching functions for both subjects resulted in higher asymptotic values, indicating an overall elevation of behavior rate under these conditions. The variance accounted for by the matching law was also higher under the medicated conditions, suggesting that their behavior more closely tracked the changing rates of reinforcement while taking MPH compared to placebo. Under medicated conditions, the reinforcing efficacy of response-contingent tokens decreased. Results are discussed with respect to quantifying behavioral changes and the extent to which the drug interacts with prevailing contingencies (i.e., schedule values) to influence behavioral variability. PMID- 11214033 TI - Testing the ability of children with attention deficit hyperactivity disorder to accurately report the effects of medication on their behavior. AB - Children with attention deficit hyperactivity disorder (ADHD) are often treated with central nervous system stimulants, making the evaluation of medication effects an important topic for applied behavior analysts. Because assessment protocols emphasize informant reports and direct observations of child behavior, little is known about the extent to which children themselves can accurately report medication effects. Double-blind placebo-controlled procedures were used to examine whether 6 children with ADHD could recognize the effects of their medication. The children were given math worksheets to complete for 15 min during each of 14 sessions while on medication and placebo. Children completed a self evaluation form at the end of each session, and ratings were compared to observed behavior and academic performance. Results indicated that 3 children were able to accurately report their medication status at levels greater than chance, whereas the accuracy of reports by all children was related to dosage level, differences in behavior, and the presence of adverse effects. The implications of these results for placebo-controlled research, self-monitoring of dosage levels, and accuracy training are discussed. PMID- 11214034 TI - Teaching self-control to small groups of dually diagnosed adults. AB - The present study examined the use of a progressive delay procedure to teach self control to two groups of dually diagnosed adults. When given a choice between an immediate smaller reinforcer and a larger delayed reinforcer, both groups chose the smaller reinforcer during baseline. During treatment, progressive increases in work requirements for gaining access to a larger reinforcer resulted in both groups selecting larger delayed reinforcers. The results are discussed with respect to increasing cooperative work behavior and self-control. PMID- 11214035 TI - Treatment of covert food stealing in an individual with Prader-Willi syndrome. AB - Covert food stealing is common among individuals with Prader-Willi syndrome. We found that verbal reprimands, delivered contingent upon eating prohibited foods, were sufficient to decrease the food stealing of a girl with Prader-Willi syndrome. Warning stimuli were then used to help her discriminate between permitted and prohibited foods during sessions in which food stealing was not directly observed. This procedure resulted in decreases in food stealing from containers labeled with the warning stimuli. PMID- 11214036 TI - The effects of a vitamin supplement on the pica of a child with severe mental retardation. AB - The effects of a common multiple vitamin on the pica of a child with severe mental retardation and anemia were evaluated. A BAB design revealed that pica was decreased by the vitamin. The results suggest that pica can be effectively treated by implementation of a simple nutritional or biological intervention. Further research investigating the generality of this finding and the effects of combining biological and behavioral interventions are discussed. PMID- 11214037 TI - The effects of noncontingent access to single- versus multiple-stimulus sets on self-injurious behavior. AB - The automatically reinforced self-injury of a girl with autism was treated by providing noncontingent access to a single set of preferred toys during 30-min sessions. The reductive effects of the intervention waned as the session progressed. Rotating toy sets after 10 min or providing access to multiple toy sets resulted in reductions that lasted the entire 30 min. PMID- 11214038 TI - Teaching children with autism to ask questions about hidden objects. AB - We taught 2 4-year-old children with autism to ask questions of an adult who held a closed box with a toy inside. The treatment package (modeling, prompting, and reinforcement) was evaluated with a multiple baseline design across the three question forms during training, generalization, and follow-up evaluations. The first question form ("What's that?") produced the name of the hidden item. The second form ("Can I see it?") produced sight of it, and the third form ("Can I have it?") produced the item itself. Both children learned to ask questions about hidden objects. PMID- 11214039 TI - Partial remediation of speaker and listener behaviors in people with severe dementia. AB - We investigated the effects of contingent reinforcement (Intervention 1) and contingent reinforcement with modeling (Intervention 2) on speaker and listener behaviors in 5 people with severe dementia. Intervention 1 generally increased listener behavior; there was no clear effect on tacting, but echoic behavior increased in the one case investigated. Given the weak baseline repertoires of these clients and the paucity of other effective interventions, even the small increases in verbal behaviors found here are important. Further gains may be achieved, for example, if reinforcement opportunity per trial type were to be increased from one to several per day or if participants were trained to echo the listener stimulus in mand compliance tasks. PMID- 11214040 TI - Motivating signage prompts safety belt use among drivers exiting senior communities. AB - Senior drivers are vulnerable to automobile crashes and subsequent injury and death. Safety belts reduce health risks associated with auto crashes. Therefore, it is important to encourage senior drivers to wear safety belts while driving. Using an AB design, replicated five times, we evaluated the short- and long-term effects of a sign with the message "BUCKLE UP, STAY SAFE" attached to a stop sign at the exits of five different senior communities. Safety belt use was stable during two pretreatment assessments averaged across the five sites and 250 drivers (72% and 68% usage), but significantly increased following installation of these signs (94% usage). Six months after installation of the signs, the effect persisted (88% usage). Use of such signs may be a cost-effective way of promoting safety belt use. PMID- 11214041 TI - Embedded evaluation of preferences sampled from person-centered plans for people with profound multiple disabilities. AB - We investigated a brief, embedded assessment for evaluating preferences sampled from person-centered plans. After developing person-centered plans for individuals with multiple disabilities, systematic assessments were conducted with preferences sampled from the plans. An assessment of sampled preferences was then embedded within the participants' daily routines. The two assessments identified similar preferences based on participant approach responses. Both assessments also indicated inconsistencies with reported preferences in the person-centered plans. Overall, results suggested the embedded assessment may be an alternative means of evaluating some preferences reported through person centered planning. PMID- 11214043 TI - Palatal fistulas: rare with the two-flap palatoplasty repair. AB - The purpose of this study was to examine the palatal fistula rate after repair with the two-flap palatoplasty technique. This is a retrospective review of 119 consecutive cleft-palate repairs performed over a 5-year interval by a single surgeon. The two-flap palatoplasty technique was used to provide tension-free, multilayer repairs. The age of these children at the time of repair ranged from 7 to 84 months (mode, 9 months). The initial follow-up visit occurred 2 to 12 weeks after the repair operation (mean, 4 weeks). The postoperative follow-up duration ranged from 7 to 48 months. This review of 119 cleft-palate repairs revealed a fistula rate of 3.4 percent (four fistulas in 119 repairs). This experience demonstrates the lowest reported palatal fistula complication rate with use of the two-flap palatoplasty technique. PMID- 11214042 TI - Repair of bilateral complete cleft lip: intraoperative nasolabial anthropometry. AB - Synchronous repair of bilateral complete cleft lip and nasal deformity requires conception of three-dimensional form and fourth-dimensional changes with growth, as distorted by the malformation. The aim is to obviate typical postoperative nasolabial stigmata. The strategy is to construct fast-growing features on a smaller scale and slow-growing features on a normal or slightly larger scale. In this study, intraoperative alterations in nasolabial dimensions were documented by anthropometry in 46 consecutive infants with bilateral complete cleft lip. These values were averaged and compared with measures from normal Caucasian infants at ages 0 to 5 months and 6 to 12 months. Nasal height (n-sn) and nasal width (al-al), both fast-growing features, were set smaller (88 percent and 96 percent, respectively) than those of age-matched normal infants. In contrast, the slow-growing features, nasal protrusion (sn-prn) and columellar length, were constructed longer than normal (130 percent and 167 percent, respectively). Because all labial features grow rapidly, they were made diminutive in this study, with the exception of central vermilion-mucosal height (median tubercle), which was purposively made full. These maneuvers resulted in a normal, average overall upper-lip height (sn-sto). Two technical refinements also are described: (1) construction of deepithelialized bands flanking the philtral flap to improve surface contour; and (2) positioning and fixation of the dislocated alar cartilages, performed entirely through superiomedial nostril rim incisions. PMID- 11214044 TI - The thersites complex in plastic surgical patients. AB - Body dysmorphic disorder describes the preoccupation with an imagined defect of appearance. A subgroup of patients suffer from the so-called Thersites complex, in which a minimal physical deformity causes excessive psychological disturbances and distress. Patients with body dysmorphic disorder tend primarily to visit a plastic surgeon for relief with distinct plans for surgical correction of their "deformity." Psychotherapy is generally refused or ineffective. The plastic surgeon should be familiar with this mental disorder and recognize these patients during consultation. Most of these patients should be excluded from surgery; however, patients of the Thersites complex category might be candidates for plastic surgical correction after careful selection. Only the experienced plastic surgeon should make the decision to operate in this situation. A successful treatment can relieve the patient from his or her distress and improve the quality of life substantially. A surgical result that is not accepted by the patient can end in a tragedy for either the patient or the doctor. PMID- 11214045 TI - Type A botulinum toxin for the treatment of hypertrophy of the masseter and temporal muscles: an alternative treatment. AB - The treatment of hypertrophy of the masseter and temporal muscles has to date been dominated by conservative and surgical measures. Local therapy with type A botulinum toxin permits an alternative method of treatment. After targeted, sometimes electromyographically controlled, intramuscular injection of the affected muscles, marked inactivity atrophy occurred in the muscles of seven patients over the course of 3 to 8 weeks. This atrophy remained constant over a follow-up period of up to 25 months, and no side effects were observed. Because of its minimal invasiveness, this technique seems to have an advantage over conventional surgical therapy. Consequently, treatment with type A botulinum toxin can be regarded as a sensible alternative to surgery in cases of hypertrophy of the masseter and/or temporal muscles. PMID- 11214046 TI - Endoscopic correction of pectus excavatum. AB - Endoscopic surgery is minimally invasive and can be used to achieve superior cosmetic results. Conventional correction of pectus excavatum results in a long scar. Correction by use of endoscopic surgery involves a smaller skin incision. In this study, endoscopic correction of pectus excavatum was performed in 20 cases. A small transverse skin incision was made above the xyphoid process. A wide area beneath the pectoralis major muscle was dissected under endoscopic visualization. Subperichondrial resection was performed under direct visualization when possible. Subperichondrial resection of the third or fourth rib was performed under endoscopic visualization. Ravitch's chondrotomy of the second or third rib was performed under endoscopic visualization. Endoscopy was also useful for sternal elevation, with minimal risk of pleural perforation. Kirschner wire was inserted percutaneously under the sternum to prevent postoperative paradoxical respiration. In all cases, the postoperative course was uneventful. The advantages of endoscopic pectus excavatum correction are a short scar, control of bleeding, safe dissection of the pleura from the sternum without the risk of pleural perforation, and ease of sternal elevation without injury to the intramammary vessels. However, the endoscopic operation is long and is not useful in adults because subperichondrial resection in adults is difficult to perform. PMID- 11214047 TI - Postoperative morphine requirements of free TRAM and DIEP flaps. AB - In a review of the charts of 158 patients who had undergone breast reconstruction with free transverse rectus abdominis musculocutaneous (TRAM) or deep inferior epigastric perforator (DIEP) flaps and who were treated for postoperative pain with morphine administered by a patient-controlled analgesia pump, the total dose of morphine administered during hospitalization for the flap transfer was measured. Patients whose treatment was supplemented by other intravenous narcotics were excluded from the study. The mean amount of morphine per kilogram required by patients who had reconstruction with DIEP flaps (0.74 mg/kg, n = 26) was found to be significantly less than the amount required by patients who had reconstruction with TRAM flaps (1.65 mg/kg; n = 132; p < 0.001). DIEP flap patients also remained in the hospital less time (mean, 4.73 days) than did free TRAM flap patients (mean, 5.21 days; p = 0.026), but the difference was less than one full hospital day. It was concluded that the use of the DIEP flap does reduce the patient requirement for postoperative pain medication and therefore presumably reduces postoperative pain. It may also slightly shorten hospital stay. PMID- 11214048 TI - Complications of postmastectomy breast reconstructions in smokers, ex-smokers, and nonsmokers. AB - Smoking results in impaired wound healing and poor surgical results. In this retrospective study, we compared outcomes in 155 smokers, 76 ex-smokers, and 517 nonsmokers who received postmastectomy breast reconstructions during a 10-year period. Ex-smokers were defined as those who had quit smoking at least 3 weeks before surgery. Transverse rectus abdominis musculocutaneous (TRAM) flap surgery was performed significantly less often in smokers (24.5 percent) than in ex smokers (30.3 percent) or nonsmokers (39.1 percent) (p < 0.001). Tissue expansion followed by implant was performed in 112 smokers (72.3 percent), 50 (65.8 percent) ex-smokers, and 304 nonsmokers (58.8 percent) (p = 0.002). The overall complication rate in smokers was 39.4 percent, compared with 25 percent in ex smokers and 25.9 percent in nonsmokers, which is statistically significant (p = 0.002). Mastectomy flap necrosis developed in 12 smokers (7.7 percent), 2 ex smokers (2.6 percent), and 8 nonsmokers (1.5 percent) (p < 0.001). Among patients receiving TR4AM flaps, fat necrosis developed in 10 smokers (26.3 percent), 2 ex smokers (8.7 percent), and 17 nonsmokers (8.4 percent). Abdominal wall necrosis was more common in smokers (7.9 percent) than in ex-smokers (4.3 percent) or nonsmokers (1.0 percent). In this large series, tissue expansion was performed more often in smokers than was autogenous reconstruction. Complications were significantly more frequent in smokers. Mastectomy flap necrosis was significantly more frequent in smokers, regardless of the type of reconstruction. Breast reconstruction should be done with caution in smokers. Ex-smokers had complication rates similar to those of nonsmokers. Smokers undergoing reconstruction should be strongly urged to stop smoking at least 3 weeks before their surgery. PMID- 11214049 TI - Incidence of hematoma associated with ketorolac after TRAM flap breast reconstruction. AB - Ketorolac is frequently used as an adjunct for postoperative pain relief, especially by anesthesiologists during the immediate postoperative period. It can be used alone as an analgesic but is more often used to potentiate the actions of narcotics such as morphine or meperidine in an attempt to reduce the total dose and side effects of those drugs. The manufacturer of ketorolac cautions against its use in patients who have a high risk of postoperative bleeding, for fear of increasing the risk of hematoma, but the risk in transverse rectus abdominis musculocutaneous (TRAM) flap patients has never been reported. In a study of 215 patients who had undergone TRAM flap breast reconstruction, it was determined that patients who received intravenous ketorolac (n = 65) as an adjunct to their treatment with morphine administered by use of a patient-controlled analgesia device required less morphine (mean cumulative dose, 1.39 mg/kg) than did patients who did not receive ketorolac (n = 150; mean cumulative dose, 1.75 mg/kg; p = 0.02). There was no increase in the incidence of hematoma in patients who were treated with ketorolac. The data presented in this study suggest that the use of intravenous ketorolac does reduce the need for narcotics administration in patients undergoing TRAM flap breast reconstruction, without significantly increasing the risk of hematoma. PMID- 11214050 TI - Calcification properties of saline-filled breast implants. AB - Three patients requested explantation of their saline-filled breast implants. Bilateral calcification had occurred in all six implants. Four of the implants were manufactured by McGhan Corporation (Santa Barbara, Calif.), and two, by the Simaplast Company (Toulon, France). All implants had been inserted in the subglandular plane and had been in place for 7 to 23 years. At the time of explantation, patients were 32, 34, and 44 years old. Calcification on the surface of the implants and capsules was analyzed. Implant surface calcification was clinically evident on all six implants, appearing as ivory-colored, tenaciously adherent deposits, only on the anterior surface of the implant. Capsular calcification, which was observed only microscopically, was characterized by poorly organized, irregularly shaped, calcified agglomerates; this calcification also occurred only on the anterior surface of the capsule, adjacent to the area of calcification on the implant. Ultrastructural analysis of scrapings from the implant surface showed large, electron-dense aggregates of crystals, with individual crystals measuring approximately 40 x 10 x 10 nm. In contrast, capsular calcification was characterized by two patterns of deposition, spherulitic aggregates of needle-shaped crystals and areas of metaplastic bone. The individual crystals were approximately 40 x 10 x 10 nm. Energy-dispersive x ray spectroscopy of specimens from the areas of calcification on the implant and capsule surfaces demonstrated calcium and phosphorus. Electron diffraction of crystals from the implant and capsule surfaces demonstrated the D-spacings characteristic of calcium apatite. There were many differences between the calcification properties of these six saline implants and those of silicone gel implants. For example, mineralization has not been observed on the surface of gel implants, but in these saline implants it occurred primarily on the implant surface. Also, capsular calcification has been observed clinically in gel implants across the surface of the capsule (except at the site of attachment of a Dacron patch), but in this study it was observed only microscopically and was located on the anterior surface of the capsule, adjacent to the area of calcification on the implant. In addition, crystals 100 times larger than those observed on the six saline implant capsules have been observed on the surface of gel implant capsules. A model is presented to explain the mechanism of calcification associated with breast implants and to explain the observed differences between saline-filled and gel-filled implants. PMID- 11214051 TI - The use of muscle flaps to treat left ventricular assist device infections. AB - Left ventricular assist devices have become an important adjunct in the therapeutic armamentarium for patients with end-stage heart failure. Although they may provide a bridge to transplantation, they are prone to certain problems, expecially infection. Because these are life-sustaining devices, changing the device or simple explantation may be a risky, if not impossible, option. Therefore, we evaluated the effectiveness of a surgical alternative, namely, coverage of infected devices with muscle or myocutaneous flaps. Eighty-two consecutive patients who underwent the insertion of 88 left ventricular assist devices at our institution over a 6.5-year period were evaluated. Follow-up was provided for all patients and ranged from 1 to 7.5 years. The duration of ventricular support ranged from 0 to 434 days. All patients who demonstrated clinical evidence of infection were identified. Overall, 54 patients (66 percent) had infections locally at the device site, at distant sites, or systemically during support. Cultured organisms included gram-positive and -negative bacteria, fungi, and viruses. Of the 56 infections in these 54 patients, 21 (38 percent) were device-related, i.e., in the pocket created by the device, in the device itself, or from the driveline. Thus, 24 percent (21 of 88) of all ventricular support devices inserted demonstrated device infection during use. Therapeutic modalities used to combat device-related infection included both nonsurgical management with antibiotics alone and surgical procedures such as device change or relocation, device explant, and flap coverage. Eight of the 20 patients in whom the 21 device-related infections occurred underwent surgical intervention. Four of these eight patients undenwent local flap coverage of their infected left ventricular assist devices. All four patients also had evidence of systemic infection, or "device endocarditis." Coverage was successfully achieved in all cases with pedicled rectus abdominis flaps. There were no perioperative complications. Two patients later underwent successful transplantation; the other two died from causes unrelated to the flap. In conclusion, the treatment of infected left ventricular assist devices currently includes both nonsurgical and surgical alternatives. Of the latter, muscle flaps should be considered a first line intervention to assist in eradicating infection by providing well vascularized tissue. Although there were no perioperative complications, the 50 percent mortality rate is consistent with that reported for patients with "device endocarditis." It may be that flap coverage of infected ventricular assist devices, if instituted at an earlier stage in the therapeutic process, could help prevent systemic infection in these patients and, therefore, improve their overall outcome. PMID- 11214052 TI - The thin latissimus dorsi perforator-based free flap for resurfacing. AB - The authors present their experience with "thin" latissimus dorsi perforator based free flaps for resurfacing defects. Perforator-based free flaps have been used for various kinds of reconstruction by presenting important donor structures. The thin latissimus dorsi perforatorbased free flap included only the skin and superficial adipose layer to reduce its bulkiness by dissection through the superficial fascial plane. This flap was used in 12 clinical cases, without flap necrosis or other serious postoperative complications. All of the patients were examined by preoperative power Doppler ultrasound in the spectral Doppler mode to search for the most reliable perforator. This noninvasive ultrasound technique determines the exact location and course of and ensures the reliable flow of the perforators; therefore, it greatly assists microsurgeons in saving operation time and in selecting the most suitable design for perforator flap reconstruction. We used perforators that were identified several centimeters from the lateral border of the latissimus dorsi muscle. The thin flap dimensions could be safely designed for flaps measuring up to 20 cm in length and 8 cm in width for primary closure of the donor site. Generally, a long pedicle is not required for resurfacing reconstructions, where small recipient arteries in the bed are acceptable for anastomosis with pedicles. However, pedicle dissection to the proximal vessels through the latissimus dorsi muscle was required when it was necessary to match the recipient vein for anastomosis. The authors conclude that this thin latissimus dorsi perforator-based free flap has great potential for resurfacing because of its constant thickness, easy elevation with the help of power Doppler ultrasound information, and proper flap size for moderate defects caused by scar contracture release, superficial tumor ablation, and so on. PMID- 11214053 TI - Comparative study of two series of distally based fasciocutaneous flaps for coverage of the lower one-fourth of the leg, the ankle, and the foot. AB - Skin defects over the lower one-fourth of the leg and over the foot are difficult to cover. Two types of pedicled fasciocutaneous flaps used to cover such defects were studied: the lateral supramalleolar flap and the distally based sural neurocutaneous flap. The series consisted of 27 and 36 cases, respectively. The lateral supramalleolar flap was used 27 times: for skin defects over the ankle (4), foot (16), and leg (7). The distally based sural neurocutaneous flap was used 42 times: over the foot (24), ankle (13), and leg (5). Fourteen of these patients were 65 years of age or older, and local vascularity was diminished in 16 cases. The flaps were evaluated clinically twice: in the immediate postoperative period for survival or for partial or total flap necrosis, and again to determine the presence of pain at the donor or recipient sites and the cosmetic appearance. Thirty-nine patients (62 percent) were reviewed subsequently, with a mean follow-up of 5 years for the supramalleolar flap and 2 years for the sural neurocutaneous flap. The results were evaluated for the presence or absence of pain, the appearance of the flap, the disability due to the insensate nature of the flap, and the presence or absence of secondary ulceration. Painful neuromata were noted in three cases with the sural neurocutaneous flap, whereas complete necrosis of the supramalleolar artery flap occurred in three patients. The distally based sural neurocutaneous island flap is very reliable, even in debilitated patients. Though the lateral supramalleolar artery flap offers the possibility of covering the same areas as the sural neurocutaneous flap, it is much less reliable in the presence of diminished local vascularity (18.5 percent failure rate as compared with 4.8 percent for the sural neurocutaneous flap). Because the procedure can cover extensive defects and is easy to perform, the distally based sural neurocutaneous flap was the method of choice for covering skin defects over the foot, heel, ankle, and the lower one fourth of the leg. The lateral supramalleolar artery flap is indicated only when the sural neurocutaneous flap is contraindicated. PMID- 11214054 TI - Do not use epinephrine in digital blocks: myth or truth? AB - The purpose of this study was to examine the role for epinephrine augmentation of digital block anesthesia by safely prolonging its duration of action and providing a temporary hemostatic effect. After obtaining approval from the review board of the authors' institution, 60 digital block procedures were performed in a prospective randomized double-blinded study. The digital blocks were performed using the dorsal approach. All anesthetics were delivered to treat either posttraumatic injuries or elective conditions. Of the 60 digital block procedures, 31 were randomized to lidocaine with epinephrine and 29 to plain lidocaine. Of the procedures performed using lidocaine with epinephrine, one patient required an additional injection versus five of the patients who were given plain lidocaine (p = 0.098). The need for control of bleeding required digital tourniquet use in 20 of 29 block procedures with plain lidocaine and in 9 of 31 procedures using lidocaine with epinephrine (p < 0.002). Two patients experienced complications after plain lidocaine blocks, while no complications occurred after lidocaine with epinephrine blocks (p = 0.23). By prolonging lidocaine's duration of action, epinephrine may prevent the need for an additional injection and prolong post-procedure pain relief. This study demonstrated that the temporary hemostatic effect of epinephrine decreased the need for, and thus the potential risk of, using a digital tourniquet (p < 0.002). As the temporary vasoconstrictor effect is reversible, the threat of complication from vasoconstrictor-induced ischemia is theoretical. PMID- 11214055 TI - Salvage of ischemic digits using a lateral arm fascial flap. AB - Four patients underwent microvascular transfer of a lateral arm fascial flap to salvage severely ischemic digits by means of induction of neovascularization. The cause of the digital ischemia was direct trauma (crush injury) in one patient and chronic embolic phenomena (proximal arterial occlusion) in three patients. None of the patients had responded to traditional therapy, including treatment with one or more of the following: anticoagulation, lytic therapy, oral vasodilators, digital sympathectomy, and vein bypass grafting. Each patient underwent noninvasive (Doppler ultrasound, digital pressures, digital temperatures, vascular refill) and invasive (angiogram) vascular assessment preoperatively. After microvascular transfer of the lateral arm fascial flap, all patients reported symptomatic relief, and objective improvements were documented by both noninvasive and invasive assessment criteria. One patient developed a seroma at the donor site; another experienced a late complication of thrombosis of the flap after his wound dehisced. A 6-month follow-up evaluation demonstrated neovascular collateralization and stable improvement without regression in the remaining patients. The authors present their clinical experience and propose a treatment algorithm for patients with chronic digital ischemia. PMID- 11214056 TI - A phase II trial of intraluminal irrigation with recombinant human tissue factor pathway inhibitor to prevent thrombosis in free flap surgery. AB - A multicenter, multinational, blinded, randomized, parallel-group, phase II study was conducted to investigate the use of recombinant human tissue factor pathway inhibitor (rhTFPI; SC-59735) as an antithrombotic additive to the intraluminal irrigating solution during microvascular anastomosis in free flap reconstructive surgery. A total of 622 patients undergoing free flap reconstruction were randomly assigned to three groups. For each group, a different intraluminal irrigating solution was administered at completion of the microvascular arterial and venous anastomoses and before blood flow to the flap was reestablished: rhTFPI at a concentration of 0.05 or 0.15 mg/ml (low-dose or high-dose group, respectively) or heparin at a concentration of 100 U/ml (current-standard-of practice group). There were no other differences in treatment among the groups. Patient characteristics, risk factors, and surgical techniques used were similar among all three groups. Flap failure was lower (2 percent) in the low-dose rhTFPI group than in the high-dose rhTFPI (6 percent) and heparin (5 percent) groups, but this difference was not statistically significant (p = 0.069). There were no significant differences in the rate of intraoperative revisions of vessel anastomoses (11 percent, 12 percent, and 13 percent) or postoperative thrombosis (8 percent, 8 percent, and 7 percent) among the low-dose rhTFPI, high-dose rhTFPI, and heparin groups, respectively. The rate of postoperative wound hematoma was significantly lower in the low-dose rhTFPI group (3 percent) than in the high-dose rhTFPI (8 percent) and heparin (9 percent) groups (p = 0.040). There were no differences in blood chemistry or coagulation values among the three study groups. Other than hematomas, there were no differences in the incidence or severity of adverse reactions among the three groups. It is concluded that use of rhTFPI as an intraluminal irrigant during free flap reconstruction is safe, well tolerated, and as efficacious as use of heparin for preventing thrombotic complications during and after the operation. Furthermore, the lower dose of rhTFPI (0.05 mg/ml) may reduce the occurrence of postoperative hematoma and help prevent flap failure. PMID- 11214057 TI - Reconstruction of the nose damaged by cocaine. AB - Nasal snorting of cocaine crystals causes destruction of the septal and nasal mucosa, which eventually provides exposure of the septal cartilage and nasal bones. This exposure eventually leads to septal chrondritis and nasal bone osteomyelitis. As this process continues, the severe loss of cartilage and bone allows gradual to total collapse of the nose. Correction of this deformity is best achieved by supplying new lining; this is possible by turning nasolabial flaps into the nasal vestibule to replace the lost and released lining. Once this has been accomplished, costal cartilage grafts can be inserted along the bridge and alae to maintain the structural integrity of the reconstruction. PMID- 11214058 TI - Inhibition of apoptosis: a potential mechanism for syndromic craniosynostosis. AB - The biologic pathogenesis of syndromic craniosynostosis remains unknown. The purpose of this investigation was to determine whether specific biologic differences exist between normal calvarial osteoblasts and osteoblasts derived from patients with syndromic craniosynostosis. This study (1) examined the apoptotic rate and cell cycle of osteoblasts derived from patients with syndromic craniosynostosis, and (2) investigated for the presence of soluble factors released from syndrome-derived osteoblasts. Osteoblast cell lines were established from calvarial specimens of patients with clinically diagnosed syndromic synostosis and from normal controls. A co-culture technique was used to investigate for the presence of elaborated soluble factors. Apoptotic rate and cell cycle analyses were performed by using flow cytometry after staining with annexin V-fluorescein isothiocyanate and propidiumiodide, respectively. The apoptotic rate was significantly reduced in syndrome-derived osteoblasts as compared with control osteoblasts. Control osteoblasts co-cultured with syndromic osteoblasts demonstrated a dramatic reduction in their apoptotic rate as compared with those co-cultured with control osteoblasts. These results indicate that osteoblasts derived from patients with syndromic craniosynostosis display a lower apoptotic rate, a normal DNA synthetic rate, and the capability to reduce the apoptotic rate in normal calvarial osteoblasts through the elaboration of soluble factors. PMID- 11214059 TI - In vitro redifferentiation of culture-expanded rabbit and human auricular chondrocytes for cartilage reconstruction. AB - To construct an autologous cartilage graft using tissue engineering, cells must be multiplied in vitro; they then lose their cartilage-specific phenotype. The objective of this study was to assess the capacity of multiplied ear chondrocytes to re-express their cartilage phenotype using various culture conditions. Cells were isolated from the cartilage of the ears of three young and three adult rabbits and, after multiplication in monolayer culture, they were seeded in alginate and cultured for 3 weeks in serum-free medium with insulin-like growth factor 1 (IGF-1) and transforming growth factor-beta2 (TGF-beta2) in three different dose combinations. As a control, cells were cultured in 10% fetal calf serum, which was demonstrated in previous experiments to be unable to induce redifferentiation. Chondrocytes from the ears of young, but not adult, rabbits, synthesized significantly more glycosaminoglycan when serum was replaced by insulin-like growth factor-1 and transforming growth factor-beta2. The number of collagen type II-positive cells was increased from 10 percent to 97 percent in young cells and to 33 percent in adult cells. Using human ear cells from 12 patients (aged 7 to 60 years), glycosaminoglycan synthesis could also be stimulated by replacing serum with insulin-like growth factor and transforming growth factor-beta. Although the number of collagen type II-positive cells could be increased under these conditions, it never reached above 10 percent. Data from five patients showed that further optimization of the culture conditions by adding ITS+ and cortisol significantly increased (doubled or tripled) both glycosaminoglycan synthesis and collagen type II expression. In conclusion, this study demonstrates a method to regain cartilage phenotype in multiplied ear cartilage cells. This improves the chances of generating human cartilage grafts for the reconstruction of external ears or the repair of defects of the nasal septum. PMID- 11214060 TI - Rat mandibular distraction osteogenesis: part III. Gradual distraction versus acute lengthening. AB - Distraction osteogenesis is a well-established method of endogenous tissue engineering. This technique has significantly augmented our armamentarium of reconstructive craniofacial procedures. Although the histologic and ultrastructural changes associated with distraction osteogenesis have been extensively described, the molecular mechanisms governing successful membranous distraction remain unknown. Using an established rat model, the molecular differences between successful (i.e., osseous union with gradual distraction) and ineffective (i.e., fibrous union with acute lengthening) membranous bone lengthening was analyzed. Herein, the first insight into the molecular mechanisms of successful membranous bone distraction is provided. In addition, these data provide the foundation for future targeted therapeutic manipulations designed to improve osseous regeneration. Vertical mandibular osteotomies were created in 52 adult male Sprague-Dawley rats, and the animals were fitted with customized distraction devices. Twenty-six animals underwent immediate acute lengthening (3 mm; a length previously shown to result in fibrous union) and 26 animals were gradually distracted (after a 3-day latency period, animals were distracted 0.25 mm twice daily for 6 days; total = 3 mm). Four mandibular regenerates were harvested from each group for RNA analysis on 5, 7, 9, 23, and 37 days postoperatively (n = 40). Two mandibular regenerates were also harvested from each group and prepared for immunohistochemistry on postoperative days 5, 7, and 37 (n = 12). In addition to the 52 experimental animals, 4 control rats underwent sham operations (skin incision only) and mandibular RNA was immediately collected. Control and experimental specimens were analyzed for collagen I, osteocalcin, tissue inhibitor of metalloproteinase-1, and vascular endothelial growth factor mRNA and protein expression. In this study, marked elevation of critical extracellular matrix molecules (osteocalcin and collagen I) during the consolidation phase of gradual distraction compared with acute lengthening is demonstrated. In addition, the expression of an inhibitor of extracellular matrix turnover, tissue inhibitor of metalloproteinase-1, remained strikingly elevated in gradually distracted animals. Finally, this study demonstrated that neither gradual distraction nor acute lengthening appreciably alters vascular endothelial growth factor expression. These results suggest that gradual distraction osteogenesis promotes successful osseous bone repair by regulating the expression of bone-specific extracellular matrix molecules. In contrast, decreased production or increased turnover of bone scaffolding proteins (i.e., collagen) or regulators of mineralization (i.e., osteocalcin) may lead to fibrous union during acute lengthening. PMID- 11214061 TI - Effect of isolation of periosteum and dura on the healing of rabbit calvarial inlay bone grafts. AB - Little is understood about the role of the recipient site in the revascularization and incorporation of autogenous inlay bone grafts in the craniofacial skeleton. Clinical experience demonstrates that secondary complex cranial vault reconstruction performed with scarred avascular dura or poor soft tissue coverage may undergo significant resorption, thus compromising the aesthetic outcome. This study was designed to determine the effect of isolating autogenous orthotopic inlay calvarial bone grafts from the surrounding dura and/or periosteum on graft revascularization, healing, and volume maintenance in the adult rabbit. Adult rabbits were randomized into four groups (n = 10 per group); in each rabbit, the authors created a circular, 15-mm in diameter, full thickness cranial defect followed by reconstruction with an autogenous calvarial bone graft, which was replaced orthotopically and held with microplate fixation. Silicone sheeting (0.5 mm thickness) was used to isolate the dura (group II), the periosteum (group II), or both dura and periosteum (group IV) from the graft interface. No silicone was placed in group I. Animals were killed 10 weeks postoperatively, and calvaria were harvested to assess graft surface area, morphology, quantitative histology, fluorochrome staining, and revascularization. Grafts isolated from both the dura and periosteum exhibited significant decreases in total bone (cortical and trabecular) surface area, blood vessel count, and interface healing compared with nonisolated control grafts. Isolation of either the dura or periosteum significantly (p < 0.05) decreased blood vessel count but had no significant effect on interface healing. Isolation of the dura alone was associated with a significant (p < 0.05) decrease in graft cross-sectional surface area and dural cortical thickness compared with nonisolated control grafts, but this effect was not observed when the periosteum alone was isolated. Quantitative histology performed 10 weeks after surgery indicated that graft isolation was associated with increased marrow fibrosis and necrosis compared with nonisolated controls; it also demonstrated evidence of increased activity in bone remodeling (osteoblast and osteocyte count, new trabecular bone, and surface resorption). Triple fluorochrome staining suggested increased bone turnover in the nonisolated grafts compared with isolated grafts at 1 and 5 weeks postoperatively. This study demonstrates that isolating a rabbit calvarial inlay autogenous bone graft from the dura and/or periosteum results in significantly (p < 0.05) decreased revascularization, interface healing, and cross-sectional areas of amount of mature bone compared with nonisolated control grafts 10 weeks after surgery. At this time point, histologic examination demonstrates a paradoxical increase in bone remodeling in isolated bone grafts compared with controls. It is possible that the inhibition of revascularization results in a delayed onset of the remodeling phase of graft incorporation. However, in the model studied, it is not known whether the quantitative histologic and morphometric parameters measured in these isolated grafts exhibit a "catch-up" phenomenon at time points beyond 10 weeks after surgery. The results of this study emphasize the importance of a healthy recipient site in the healing and incorporation of calvarial bone grafts but stress the need for further investigation at later time points. PMID- 11214062 TI - Eversion with four sutures: an easy, fast, and reliable technique for microvascular anastomosis. AB - In this study, a microvascular anastomosing technique called "eversion with four sutures" is introduced. For microvascular anastomosis, this technique requires fishmouth incisions at both vessel ends and the completion of four sutures. In 120 Wistar-Albino rats, 120 eversion and 120 conventional anastomoses were done in 240 femoral arteries. Each rat received both treatments. Operating time, bleeding time, number of sutures used, patency rates, and pseudoaneurysm formation were analyzed statistically; healing was evaluated with both light and electron microscopy. When compared with the conventional technique using nine sutures, the eversion with four sutures technique was found to be a faster and easier method of anastomosis and as reliable as the conventional technique. Without compromising patency rates, bleeding time, or rates of pseudoaneurysm formation, anastomosis time and amount of suture material exposed to the lumen were significantly reduced when using this technique. In conclusion, the authors think that eversion with four sutures is a reliable alternative to the conventional suturing technique, especially for emergency cases that require multiple microvascular anastomoses. PMID- 11214064 TI - Dynamic rectus abdominis muscle sphincter for stoma continence: an acute functional study in a dog model. AB - Fecal stomal incontinence is a problem that continues to defy surgical treatment. Previous attempts to create continent stomas using dynamic myoplasty have had limited success due to denervation atrophy of the muscle flap used in the creation of the sphincter and because of muscle fatigue resulting from continuous electrical stimulation. To address the problem of denervation atrophy, a stomal sphincter was designed using the most caudal segment of the rectus abdominis muscle, preserving its intercostal innervation as well as its vascular supply. The purpose of the present study was to determine whether this rectus abdominis muscle island flap sphincter design could maintain stomal continence acutely. In this experiment, six dogs were used to create eight rectus abdominis island flap stoma sphincters around a segment of distal ileum. Initially, the intraluminal stomal pressures generated by the sphincter using different stimulation frequencies were determined. The ability of this stomal sphincter to generate continence at different intraluminal bowel pressures was then assessed. In all cases, the rectus abdominis muscle sphincter generated peak pressures well above those needed to maintain stomal continence (60 mmHg). In addition, each sphincter was able to maintain stomal continence at all intraluminal bowel pressures tested. PMID- 11214063 TI - Vanadate ingestion increases the gain in wound breaking strength and leads to better organized collagen fibers in rats during healing. AB - Repair of incision wounds closed by suturing is evaluated by the progressive gain in wound breaking strength. Previously the closure of open wounds in rats ingesting vanadate, an inhibitor of tyrosine phosphate phosphatases, was shown to occur with deposition of more uniformly organized collagen fiber bundles. The hypothesis of this study was that deposition of more uniformly organized collagen fibers would enhance the gain in wound breaking strength of incisional wounds. Six adult rats received vanadate-supplemented saline drinking water for 1 week before placement of two 6-cm, parallel, suture-closed wounds on their backs. Six control rats received identical wounds and were given saline drinking water. The drinking water regimen was continued for 1 week after wounding, and then wound strength was tested with a tensiometer and tissue samples were obtained for histologic evaluation. Wound breaking strength doubled in vanadate-treated rats compared with controls. Bright-field and polarized light microscopy showed that the connective tissue matrix of granulation tissue from control rats was oriented perpendicular to the surface of the skin. In contrast, the connective tissue matrix of granulation tissue from vanadate-treated rats was oriented parallel to the skin surface. The gap in granulation tissue between the edges of the wounds in the vanadate-treated rats was greater than that in controls. Electron microscopy showed that wounds in the vanadate-treated contained uniform collagen fibers that were 20 percent greater in diameter and more evenly spaced than they were in controls. It is proposed that these changes in the organization of collagen fibers within incisional wounds were responsible for the increased wound breaking strength observed in rats ingesting vanadate. PMID- 11214066 TI - Heterotopic brain tissue in the scalp. PMID- 11214065 TI - Tissue engineering of peripheral nerves: A comparison of venous and acellular muscle grafts with cultured Schwann cells. AB - Bioengineering is considered to be the laboratory-based alternative to human autografts and allografts. It ought to provide "custom-made organs" cultured from patient's material. Venous grafts and acellular muscle grafts support axonal regeneration only to a certain extent because of the lack of viable Schwann cells in the graft. We created a biologic nerve graft in the rat sciatic nerve model by implanting cultured Schwann cells into veins and acellular gracilis muscles, respectively. Autologous nerve grafts and veins and acellular muscle grafts without Schwann cells served as controls. After 6 and 12 weeks, regeneration was assessed clinically, histologically, and morphometrically. The polymerase chain reaction analvsis showed that the implanted Schwann cells remained within all the grafts. The best regeneration was seen in the control; after 12 weeks the number of axons was increased significantly compared with the other grafts. A good regeneration was noted in the muscle-Schwann cell group, whereas regeneration in both of the venous grafts and the muscle grafts without Schwann cells was impaired. The muscle-Schwann cell graft showed a systematic and organized regeneration including a proper orientation of regenerated fibers. The venous grafts with Schwann cells showed less fibrous tissue and disorganization than the veins without Schwann cells, but failed to show an excellent regeneration. This might be attributed to the lack of endoneural-tube-like components serving as scaffold for the sprouting axon. Although the conventional nerve graft remains the gold standard, the implantation of Schwann cells into an acellular muscle provides a biologic graft with basal lamina tubes as pathways for regenerating axons and the positive effects of Schwann cells producing neurotrophic and neurotropic factors, and thus, supporting axonal regeneration. PMID- 11214067 TI - Computer-Assisted sensorimotor testing documents neural regeneration after ulnar nerve repair at the wrist. PMID- 11214068 TI - Bipedicled fronto-occipital flap for reconstruction of postoncologic defects of the lateral scalp. AB - Presented here are two clinical cases of extensive defects of the scalp secondary to surgical resection of invasive basal cell carcinoma on the parietal region, successfully treated by means of very large, bipedicled fronto-occipital flaps, based anteriorly on the supratrochlear-supraorbital vessels and posteriorly on the occipital and posterior auricular vessels. Considering both the location and the large size of the scalp defects, different surgical techniques are discussed and the potential use of bipedicled scalp flaps is considered, designed either sagittally or coronally as fronto-occipital or temporo-temporal flaps. The bipedicled fronto-occipital scalp flap is believed to represent a simple, secure, and useful reconstructive procedure for cutaneous coverage of extensive defects located on the lateral scalp. PMID- 11214069 TI - A contemporary correction of inverted nipples. PMID- 11214070 TI - Distal arteriovenous fistula to maintain patency of the venous drainage of a latissimus dorsi flap following subclavian vein repair. AB - Successful reconstructive surgery with muscle flaps depends on adequate arterial supply and undisturbed venous drainage. Combining such surgery with reconstructive vascular surgery of a large-caliber vein that is responsible for the venous drainage of the flap poses an additional challenge--the repaired vein's susceptibility to thrombosis. Every attempt must be made to prevent venous outflow obstruction following muscle flap surgery. Data from the vascular surgery literature demonstrate a low success rate for subclavian vein repair. The success rate with venous reconstructive surgery has been greater when a distal arteriovenous fistula accompanied the repair. The present case described the use of a temporary distal cephalic-brachial arteriovenous fistula to maintain the patency of the venous drainage of a pedicled latissimus dorsi muscle flap, following subclavian vein repair, for one-stage coverage of a large chest wall defect. PMID- 11214071 TI - The leech pond: a translation and commentary on the notes of Professor Luigi Zersi. PMID- 11214072 TI - New developments in cranial suture research. PMID- 11214073 TI - Breast cancer: advances in surgical management. AB - The surgical management of breast cancer has changed dramatically from a deforming ablative procedure to an approach that for the majority of breast cancer patients can preserve the breast and axillary anatomy. The current approach to the diagnosis of breast cancer and the evolution of the more limited approach to surgical resection are discussed. The technique of sentinel lymph node biopsy, originally developed for melanoma patients, has now been adopted for use in the treatment of breast cancer. The methodology and advantages of this approach to the axillary lymph nodes in both tumor recognition and reduced risk to the patient are detailed. PMID- 11214074 TI - A lifelong journey and passion: maintaining clinical competence in plastic surgery. PMID- 11214075 TI - AlloDerm for dorsal nasal irregularities. AB - After nasal surgery, thinning of the nasal skin, bony irregularities, or adhesions of dorsal skin to underlying bone can all occur. These problems can be solved by using either alloplastic materials or various autogenous tissues. In this study, AlloDerm, a dermal replacement derived from cadaveric skin, has been used to cover the osseocartilaginous framework of the nose in an attempt to achieve a smooth contour and a natural feel in secondary rhinoplasties. Fifteen patients were treated and observed for a minimum of 24 months. Clinically palpable or visible bony irregularities were successfully covered, and adhesions of dorsal skin to nasal bones were diminished. Prolonged but not socially unacceptable dorsal nasal swelling, which resolved during the first 4 months, seemed to be the only problem related to its use. With this limited experience, AlloDerm was found to be useful in secondary nasal surgery to cover osseocartilaginous irregularities, to eliminate the adhesions between nasal bones and overlying skin, and to create a smooth nasal dorsum. PMID- 11214076 TI - The use of alloderm for the correction of nasal contour deformities. AB - What rhinoplasty surgeon has not been frustrated by unmet expectations from unreliable graft materials? The quest for an ideal graft continues. Septal cartilage is not always adequate in amount or substance. Ear cartilage may cause unsightly irregularities over time. Cranial bone or rib harvest sites add to the complexity of the procedure and can be intimidating for many operators. This article describes the authors' successful experience with AlloDerm onlay grafts for the correction of nasal contour deformities in 58 primary and secondary rhinoplasty cases by means of the open and endonasal approaches. Forty-two patients received an open-approach procedure; the remaining 16 received grafting through an endonasal or closed approach. Thirty-seven of the patients were secondary rhinoplasty patients, and some underwent multiple nasal corrections. The indications, intraoperative surgical technique of graft placement, and representative results will be discussed. Long-term follow-up showed good results, though partial graft resorption occurred in some patients. Overall, this experience with AlloDerm for nasal augmentation was encouraging. PMID- 11214077 TI - The sit-up position in breast surgery. AB - Breast shape is best evaluated while the patient is in an upright position. However, many surgeons are reluctant to have a patient sit upright during surgery because of concerns over the patient's hemodynamic instability. Therefore, the purpose of this study was to prospectively measure cardiovascular parameters, including heart rate and mean arterial pressure, in a series of 30 patients who were placed upright during various aesthetic and reconstructive breast procedures. Data regarding the number of times the patient was placed upright and the amount of time spent in the upright position were also recorded. Measurements were obtained immediately before and after elevating the head of the bed to 80 to 90 degrees during the procedure. The average supine mean arterial pressure was 73 +/- 3 mmHg and that for an upright position was 70 +/- 3 mmHg. The average supine heart rate was 73 +/- 4 beats per minute and that for an upright position was 76 +/- 4 beats per minute. Although the difference between these results is statistically significant (p < 0.05), there was no clinical significance to placing patients in an upright seated position in this study, and no patient had to be laid back down because of hemodynamic instability. Therefore, the upright seated position is strongly advocated for intraoperative evaluation of breast shape, and a safe and effective method to accomplish this is described. PMID- 11214078 TI - The "Nordstrom suture" to enhance scalp reductions. AB - The authors compared the results of 10 scalp reductions using the "Nordstrom suture" with the earlier published results of scalp reductions without a device to prevent stretch-back and of reductions with extenders. At 1 month postoperatively, the Nordstrom suture eliminated the stretch-back of 8.3 mm seen in earlier studies and, in fact, it shrank the bald area. The average shrinking achieved with the Nordstrom suture was 16.9 mm (i.e., 143 percent improvement over scalp reductions alone). Scalp extenders shrank the bald area, but the Nordstrom suture shrank the area about three times more than extenders at 1 month postoperatively. PMID- 11214079 TI - Combined erbium:YAG laser resurfacing and face lifting. AB - Facial aging occurs secondary to gravity-induced tissue ptosis and photoaging. Combined face lifting and carbon dioxide laser resurfacing provides a comprehensive one-stage approach to facial rejuvenation but is condemned by many plastic surgeons due to the nonspecific thermal effects of the laser and risk of skin necrosis. Newer high-energy erbium:YAG lasers allow precise tissue ablation with minimal thermal effect. In this study, various facial rejuvenation techniques were combined with simultaneous erbium:YAG laser resurfacing to assess results and complications. A total of 257 patients from Florida, Melbourne, Australia, and Tel Aviv, Israel, underwent combined erbium:YAG laser resurfacing and surgical facial rejuvenation. Various face-lift methods were used, including endoscopic, deep plane, and subcutaneous. Simultaneous, full-facial laser resurfacing was performed using a variety of erbium:YAG lasers. It was found that combined laser resurfacing and face lifting was successful in greater than 95 percent of patients with minimal morbidity. Two patients (1 percent) (both heavy smokers) developed small areas of skin necrosis that healed with minor pigment changes. Five patients (2 percent) developed synechia that was treated with no residual effect. Two additional patients (1 percent) developed temporary ectropion. There were no other cases of scarring, infection, or cosmetically obvious hypopigmentation. Although larger studies are necessary, it seems that the lack of thermal injury from the erbium:YAG laser makes it possible to safely perform laser resurfacing with surgical facial rejuvenation in nonsmokers. However, the authors caution that familiarity with the nuances of erbium:YAG laser resurfacing be obtained before performing combined laser resurfacing and face lifting. PMID- 11214080 TI - A novel device for the simple and efficient refinement of liposuctioned tissue. AB - In short, our device allows a surgeon who is harvesting adipose tissue for autologous fat transplantation to immediately, easily, efficiently, and sterilely isolate adipose tissue from the unwanted waste components that are associated with primary liposuction effluent. It does so by "trapping" the fat tissue contained within raw liposuction effluent. Once the tissue fraction has been separated, the device design then allows for direct implantation or subsequent washing/rinsing of the tissue with saline/buffer of choice in preparation for tissue reimplantation. PMID- 11214081 TI - A lesson from the high-tech economic boom: use the competitive advantage of plastic surgery. PMID- 11214082 TI - Corrugator supercilii resection through blepharoplasty incision. PMID- 11214083 TI - Sucking fat: an 18-year statistical and personal retrospective. PMID- 11214084 TI - Coblation: an emerging technology and new technique for soft-tissue surgery. PMID- 11214085 TI - Progressive tension sutures to reduce complications in abdominoplasty. PMID- 11214086 TI - Technique for isolating ruptured extensor pollicis longus tendon. PMID- 11214087 TI - The distally based dermo-adipofascial flap. PMID- 11214088 TI - Aspirin and elective surgery. PMID- 11214089 TI - A missed opportunity? PMID- 11214090 TI - Amnion tube for nerve regeneration. PMID- 11214091 TI - External device for adipose tissue. PMID- 11214092 TI - Tail bone in the rat. PMID- 11214093 TI - In-vivo sensitivity of Plasmodium vivax isolates from Rond nia (western Amazon region, Brazil) to regimens including chloroquine and primaquine. AB - Seventy-nine adults with Plasmodium vivax malaria, from the Porto Velho area of Rond nia (western Amazon region, Brazil), gave informed consent to participate in a blind, clinical study of two regimens of treatment with chloroquine (CQ) and primaquine. The effectiveness of the 'classical' regimen (CQ for 3 days, followed by primaquine for 14 days) was compared with that of a 'short' regimen in which the two drugs were given simultaneously for 5 days. There were no cases of recrudescence indicative of CQ resistance (i.e. within 30 days of the first treatment dose) among the 73 patients who each completed a full, supervised course of treatment. However, 10 cases of apparent relapse were observed (all > 60 days after first treatment dose), representing 6.5% (2/31) of the patients who completed 60 days of follow-up after the classical treatment and 26.7% (8/30) of the short-regimen patients who completed the same period of follow-up. PCR-based comparison of parasitic DNA collected pre- and post-treatment was successful for eight of the 10 cases of apparent relapse and indicated that two such cases, both given the short regimen of treatment, were, in fact, probable cases of re infection rather than of relapse. The results indicate that the classical schedule of treatment with chloroquine and primaquine was more effective at preventing relapses than the short regimen. However, since prolonged treatment with primaquine often produces side-effects that are severe enough to reduce compliance, the short schedule could be a useful alternative for malaria control in endemic areas of the Amazon region. PMID- 11214094 TI - Chloroquine prophylaxis, iron/folic-acid supplementation or case management of malaria attacks in primigravidae in western Uganda: effects on congenital malaria and infant haemoglobin concentrations. AB - A randomized, double-blind, placebo-controlled trial, which compared the effects of three interventions (weekly chloroquine prophylaxis, daily iron and weekly folic-acid supplementation, and case management of malaria) on congenital malaria, maternal haemoglobin (Hb) and foetal outcome, was conducted among primigravidae resident in Hoima district, Uganda. Among 473 babies examined at birth or within 7 days of birth, 198 (42%) were parasitaemic, the level of parasitaemia in an infant being strongly correlated with those of placental (P< 0.01) and maternal, peripheral parasitaemia (P < 0.01). However, 33 (17%) of the parasitaemic babies were born to mothers who had placental but not peripheral parasitaemia, 22 (11%) to mothers who had peripheral but not placental parasitaemia, and 12 (6%) to mothers with neither peripheral nor placental parasitaemia. Overall, 163 babies were each examined for malarial parasites at birth and 1 month later. Of the 76 (47%) found to have parasitaemia at birth, 37 (23%) appeared aparasitaemic at the 1-month follow-up but 28 (17%) were still parasitaemic at that time. Among the babies born to the mothers who only received case management of malaria during pregnancy, parasitaemia at birth was associated with infant anaemia at birth (i.e. < 140 g Hb/litre; P = 0.03). Infants found to be parasitaemic at the 1-month follow-up had lower mean concentrations of Hb at that time than their aparasitaemic counterparts (P= 0.03). Parasitaemia at birth was not significantly associated with low birthweight, in any of three intervention groups. The intervention given to the mother had no significant effect on the parasitaemia of her baby, either at birth or at the age of 1 month. Congenital malaria per se may have little influence on birthweight but may have an impact on infant anaemia. In conclusion, congenital parasitaemia was not associated with birthweight, but was related to anaemia at birth in infants born to women who had only received active case management during their pregnancies. PMID- 11214095 TI - Incidence and management of malaria in two communities of different socio economic level, in Accra, Ghana. AB - Two adjacent communities of differing socio-economic levels were selected, in Accra, Ghana, for the study of the home management of malaria. The youngest child in each selected household, each of which had a child aged < 5 years, was recruited for weekly follow-up, following informed consent. Malaria was the most common condition reported by the 'caregivers' (mothers of the subjects and others caring for the subjects) in each community, with 2.0 episodes of clinical malaria/child during the 9-month study. Most (89%) of the caregivers in the better-off community had been educated beyond primary-school level, but 55% of the caregivers in the poorer community had either received no formal education or only primary-school education. This difference was also reflected by the educational facilities provided to the children studied: 52% of the those in the better-off community attended nurseries, kindergartens or creches, compared with 8% of the children investigated in the poorer community. The proportion of caregivers who purchased drugs without prescription or used left-over drugs to treat clinical malaria in the children was higher in the poorer community (82% v. 53%), and a child from the poorer community was less likely to have been taken to a clinic or hospital to be treated for malaria than a child from the better-off community (27% v. 42%). During the follow-up period two children died, one from each community. Treatment of malaria in young children is likely to be less effective in the poorer community, where a lack of economic access to health services was demonstrated. PMID- 11214096 TI - Cutaneous leishmaniasis in Guatemala: people's knowledge, concepts and practices. AB - Ten rural communities in the northern area of Guatemala where cutaneous leishmaniasis (CL) is endemic were investigated to determine the residents' knowledge of the disease, their related concepts and practices, and their treatment preferences, and to identify the communication channels they use to acquire information. Of 425 heads of household interviewed, 96.7% could accurately describe a typical CL lesion. CL was found to be the fourth most frequently mentioned disease (in studies based on a free list format) and to be considered the sixth most serious (in studies based on paired comparisons). A series of three-way comparisons, used to analyse the subjects' concepts about the similarities of various discases, indicated that CL was considered to be most closely related to skin problems and to be different from any other group of diseases. All interviewees believed that it was necessary to receive treatment for CL, because without treatment the disease would progress, reach the bone, and take years to heal. More than half (55%) of the respondents knew about meglumine antimonate (Glucantime), the most commonly prescribed drug for treating CL in Guatemala. Only a few communication channels that were used by respondents to receive information were identified; the use of radio broadcasts and direct communication via the community leaders appeared to be the most effective. PMID- 11214097 TI - Effects of itraconazole and terbinafine on Leishmania major lesions in BALB/c mice. AB - The effects of two antifungal compounds, the azole itraconazole and the allylamine terbinafine, on Leishmania major infections in mice are reported. Sixty BALB/c mice were each inoculated subcutaneously with metacyclic promastigotes of L. major at the base of the tail. From 4 weeks post-inoculation, 40 of the mice were treated for 4 weeks (20 with itraconazole and 20 with terbinafine) and the rest were left untreated. Lesion sizes were estimated weekly for 10 weeks post-infection. Both drugs appeared effective in treating the cutaneous lesions but response to itraconazole was faster and, at the end of the experiment, the mean size of the lesions on the mice treated with itraconazole was smaller than that of the lesions on the terbinafine-treated mice. PMID- 11214098 TI - Clinical and parasitological aspects of itching caused by onchocerciasis in Morogoro, Tanzania. AB - A clinical and parasitological assessment of onchodermatitis was conducted in a rural area of Morogoro district, Tanzania. The study population consisted of 1,005 individuals aged > or = 5 years: 749 from a hyper-endemic community and 256 from a hypo-endemic. The prevalence of troublesome itching was 67.0% in the hyper endemic community but only 5% (13/256) in the hypo-endemic. The corresponding prevalences of nodules among the adult male subjects were 77.7% (171/220) and 2.3% (2/86). The most common onchocercal skin lesion in the hyper-endemic community was chronic papular onchodermatitis (CPOD) manifested by itching, which was often very severe. There was a strong association between skin itching and endemicity (r = 0.75; P < 0.001). The prevalence of CPOD in the hyper-endemic community was significantly higher in males than females (P< 0.001). CPOD was only observed in subjects aged > or = 7 years. Many of the subjects were checked for microfilaridermia, by skin-snipping. The prevalence of microfilaridermia [58.2% (393/675) v. 6.2% (3/48)] and its geometric mean intensity (8.9 v. 1.0 microfilariae/mg skin snip) were both higher in the hyper-endemic community than the hypo-endemic. Itching appears to be related to reactive onchodermatitis. PMID- 11214099 TI - Antibiotics and Wolbachia in filarial nematodes: antifilarial activity of rifampicin, oxytetracycline and chloramphenicol against Onchocerca gutturosa, Onchocerca lienalis and Brugia pahangi. AB - The activity against filarial parasites of the antibiotics rifampicin, oxytetracycline and chloramphenicol was examined. In addition, transmission electron microscopy was used to study the effects of rifampicin and oxytetracycline on filarial tissues and on the endosymbiont bacterium, Wolbachia. When tested in vitro at a concentration of 50.0 microM, each of the three antibiotics significantly reduced the motility levels of male Onchocerca gutturosa. Rifampicin, however, was the most active, virtually immobilizing the parasite by the end of the 40-day trial and producing an 84% reduction in viability (as measured by formazan-based colorimetry). In tests against O. lienalis microfilariae (mff) in CBA mice, the numbers of mff recovered after treatment with oxytetracycline at 100, 25 or 6.5 mg/kg daily, for 15 days, were 56% (P < or = 0.03), 38% (P> 0.05) and 45% (P = 0.05) less than that recovered from the untreated controls, respectively. In another trial in mice, rifampicin (100 mg/kg daily for 15 days) was found to be the most active (causing a 74% reduction in the number of mff recovered--approximately equal to that achieved with the positive control of a single dose of ivermectin at 2 microg/kg), with chloramphenicol also showing significant activity (39% reduction). In further, in vivo trials, at three dose levels (100, 25 or 6.25 mg/kg daily, for 15 days), all three antibiotics were tested against adult Brugia pahangi in the peritoneal cavities of jirds. None of the antibiotics produced a significant reduction in the numbers of live worms recovered, although a marginal effect was observed in eight of the nine antibiotic-treated groups. A further extended trial with rifampicin and oxytetracycline resulted in 43% and 38% reductions in worm recoveries, respectively (not statistically significant but consistent with a marginal effect); some of these worms appeared less motile and qualitatively in poor condition compared with those recovered from untreated jirds. Ultrastructural studies of these treated worms revealed that virtually all of the endosymbiont bacteria had been cleared from the parasite tissues. The tissues of the adult worms appeared to be largely intact but with a granulomatous response of host cells adhering to some specimens. However, developing uterine forms appeared to be abnormal and extensively damaged, showing an abrogation of embryogenesis. In contrast, worms recovered from control animals contained large numbers of Wolbachia, had no adherent host cells, and showed normal ultrastructure; the female worms exhibited a full range of intra-uterine developing stages from eggs to stretched mff. It is likely that the activity of these antibiotics against the endosymbiont Wolbachia causes the observed antifilarial activity, although some direct effect of each drug on filarial viability cannot be ruled out. PMID- 11214100 TI - Morbidity and mortality among Egyptian neonates and infants: rates and associated factors. AB - Among 2,128 women residing in two Egyptian governorates with differing socio economic backgrounds, who were interviewed after giving birth between 1994 and 1996, 181 experienced an early foetal death, 34 had stillbirths, and 1,908 each had a live birth. Among the live births, there were 35 neonatal deaths and 42 post-neonatal deaths. A high percentage of the women sought prenatal care, beginning early in pregnancy, from both government health facilities (GHF) and private physicians. Problem-based care was typically directed to private physicians whereas routine care was largely directed to GHF. Diagnostic procedures were not routinely performed at GHF. The women recognized symptoms which may be associated with adverse outcomes, but health-seeking based on this recognition was inconsistent. Most deliveries were conducted by Egyptian traditional birth attendants, in homes. Anaesthesia and medications to accelerate labour were commonly administered by all types of practitioners in home deliveries. Perinatal mortality was mid-range by global standards, with most deaths occurring at home rather than in hospitals. Although care was sought for most infants with diarrhoea, respiratory infections and fever, neonates with these symptoms were rarely given oral rehydration therapy or antibiotics. PMID- 11214101 TI - Clinical and biological evolution of human trypanosomiasis in C te d'Ivoire. PMID- 11214102 TI - Human infections with Moniliformis moniliformis (Bremser 1811) Travassos 1915 in south-eastern Nigeria. PMID- 11214104 TI - International training of doctors in maritime health. PMID- 11214103 TI - The present state and prospects of development of maritime medicine in Ukraine. AB - In this article the present situation, tasks, and prospects of development of maritime in Ukraine are reviewed. Some information about morbidity and mortality among seafarers is also provided. PMID- 11214105 TI - The seafarers' opinions on the increasing influence of their administrative work on ship safety. PMID- 11214106 TI - Maritime health services in the Ivory Coast. PMID- 11214107 TI - Deaths due to disease of seafarers on board Singapore ships. AB - Based on records kept in the Singapore Mercantile Marine Office, the paper presents the results of a study on deaths due to disease of seafarers on board Singapore ships. Out of a total of 373 deaths, altogether 69 fatalities were attributed to diseases. More than 65% (n=45) of theses deaths were due to circulatory diseases commonly associated with life-style factors, but only 24 cases had a specific and 9 cases had an unspecific diagnosis confirmed by a medical, practitioner. A total of 32 seafarers (46.4%) died of a sudden death and were found dead by their shipmates whereas 17 seafarers (24.6%) died on board after a short illness. In only two cases was it reported that Radio Medical advice had been sought indicating either a lack of interest of the ship's management or a lack of knowledge or information on the availability of such services. Eight of the fatalities who died on board had seen a doctor and been declared fit to stay on board, pointing to deficiencies in the port medical services or pressures on port doctors to avoid a costly repatriation. The mean annual mortality rate for deaths due to all causes was 26.5 per 10,000 seafarers and due to disease was 4.9 per 10,000 seafarers. PMID- 11214108 TI - Liver injury in the course of malaria. AB - 121 malaria cases treated in the Ward of Tropical Diseases of the Clinic of the Institute of Maritime and Tropical Medicine in Gdynia in the years 1993-1999 were analysed. About 37% of the patients showed symptoms of parenchymal liver injury manifested by increased bilirubin concentration, elevated transaminase, alkaline phosphatase and GGTP levels. Histopathological examination of the liver revealed the activation of cells of mononuclear phagocyte system, Kupffer's cells in particular, with the presence of granules of browny-black ,,malarial" pigment and iron deposits. In one fatal tropical malaria case, symptoms of disseminated intravascular coagulation were found along with a few lymphocytic infiltrations in portal spaces, and focal necrosis of hepatocytes. In some patients with the so called ,,untypical" secondary liver lesions present in the histopathological examination, the toxic effect of antimalarial drugs should be taken into account. A liver biopsy is justified in patients manifesting multiple courses of malaria. It is indispensable in cases of suspected polyetiological changes in the liver and in cases of recompensation payment claims. PMID- 11214110 TI - Travel medicine in Poland an overview. PMID- 11214109 TI - Evaluation of methods of sewage treatment on board of vessels on the basis of surveys in 1994-1999. AB - The purpose of the present study was to show in what degree the ships of the Polish merchant fleet observe the obligations provided for Poland by acts of good will of nations, i.e. International Convention for the Prevention of Pollution from Ships -MARPOL 73/78 - Annex IV, and the Helsinki Convention. The examinations involved ships equipped with sewage treatment and disinfection plants, the surveys were performed during their normal operation. The tests were made in accordance with the resolution MEPC-2(VII) and encompassed: determination of residual available chlorine (on board vessel, immediately after sampling), determination of faecal coli index and suspended solids, determination of biochemical oxygen demand (in laboratory conditions). Results of the tests were evaluated according to the above mentioned Resolution. From 1994 to 1999, the total of 245 surveys were made, 177 sewage treatment plants were evaluated, 173 certificates were issued (in that number 125 permanent and 48 temporary). It was stated that Polish ships were properly equipped and well prepared to comply with the obligations provided by international conventions. A conclusion was formulated that the curriculum of higher maritime schools should be broadened in respect of environment protection issues. PMID- 11214111 TI - Diagnosing and treatment of skin filariases based on own observations. AB - 7 cases of Mansonella perstans filariasis and 9 of Loa loa invasion were diagnosed and treated in the clinic of the Institute of Maritime and Tropical Medicine in Gdynia in the years 1993-1999. The study group comprised 7 women aged 15-45 and 19 men aged 32-49. The most frequently occurring symptoms and signs of the disease, results of laboratory tests, diagnostic methods, ways of treatment and their efficacy were discussed. The diagnosis was made on the basis of the presence of filaria larvae in peripheral blood and, in part, on positive serological reactions. The most frequently reported and observed in our patients were Calabar swellings, allergic lesions of the skin and general symptoms. In the laboratory tests the most characteristic were elevated white blood cells counts with marked eosinophilia and a rise in immunoglobulin E during the active phase of the disease. In doubtful cases, Mazzotti's test was applied. In spite of the treatment with DEC lasting for 3-4 weeks and a combined therapy with levamisole and albendazole, relapses occurred in 5 cases in the period from 2 months to 2 years after the completion of the therapy. In 3 patients treated with ivermectin the period of observation was still too short (2 and 5 months) to draw conclusions as to the efficacy of such treatment. PMID- 11214112 TI - Diseases, accidents and injuries among travelers in Poland. AB - A survey was conducted among a group of people who traveled from Poland abroad, and who were insured before leaving the country, and in case of illness or injury claimed the costs of treatment providing medical documentation. The risk of disease and injury among these travelers was estimated. Among 336,254 travelers, there were 2,411 cases of disease and 789 cases of injury, during their mean period of travels and stay abroad of about 3 weeks (20,63 days). In the surveyed group, there were 24 cases of fatal disease and 7 cases of fatal injuries recorded. The incidence per 100,000 was calculated. PMID- 11214113 TI - Drowning among Polish boat and cutter fishermen as a specific cause of death at sea. PMID- 11214114 TI - Recreational diving--an overview of selected medical aspects. AB - Recreational diving has become very popular in Croatia. Selected medical aspects of it are reviewed in this article. PMID- 11214115 TI - Health examinations of seafarers--whose interests are we taking care of? PMID- 11214116 TI - The International Radio Medical Centre (C.I.R.M.): an organization providing free medical assistance to seafarers of any nationality world wide. AB - The International Radio Medical Centre (Centro Internazionale Radio Medico, C.I.R.M.) was founded in 1935 with the purpose of giving radio medical advice to ships on any nationality navigating on all seas of the world. The Centre has its headquarters in Rome, and its medical services are completely free of charge. They also include arrangements for the transfer, if necessary, of a patient to a ship with a doctor on board or if the distance allows it, to evacuate the patient for hospitalization. Requests for medical advice reaching C.I.R.M. are handled by doctors on continuos duty at the C.I.R.M. headquarters. These doctors advice on the appropriate treatment and keep in contact with every ship that has asked for assistance, following up the progress of the patient until his recovery or evacuation to the hospital on shore. PMID- 11214117 TI - Health care for seafarers in Indonesia. PMID- 11214118 TI - The Research Unit of Maritime Medicine Esbjerg, Denmark. PMID- 11214119 TI - World trade rules and cheaper drugs. PMID- 11214120 TI - Toxicity of depleted uranium. PMID- 11214121 TI - Relation between colitis and colon cancer. PMID- 11214122 TI - Glusoamine for osteoarthritis: dawn of a new era? PMID- 11214123 TI - Hyperplastic callus and osteogenesis imperfecta. PMID- 11214124 TI - Towards a genomic-based diagnosis. PMID- 11214125 TI - To blow or not to blow? PMID- 11214126 TI - Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. AB - BACKGROUND: Treatment of osteoarthritis is usually limited to short-term symptom control. We assessed the effects of the specific drug glucosamine sulphate on the long-term progression of osteoarthritis joint structure changes and symptoms. METHODS: We did a randomised, double-blind placebo controlled trial, in which 212 patients with knee osteoarthritis were randomly assigned 1500 mg sulphate oral glucosamine or placebo once daily for 3 years. Weightbearing, anteroposterior radiographs of each knee in full extension were taken at enrolment and after 1 and 3 years. Mean joint-space width of the medial compartment of the tibiofemoral joint was assessed by digital image analysis, whereas minimum joint-space width- ie, at the narrowest point--was measured by visual inspection with a magnifying lens. Symptoms were scored by the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index. FINDINGS: The 106 patients on placebo had a progressive joint-space narrowing, with a mean joint-space loss after 3 years of 0.31 mm (95% CI -0.48 to -0.13). There was no significant joint-space loss in the 106 patients on glucosamine sulphate: -0.06 mm (-0.22 to 0.09). Similar results were reported with minimum joint-space narrowing. As assessed by WOMAC scores, symptoms worsened slightly in patients on placebo compared with the improvement observed after treatment with glucosamine sulphate. There were no differences in safety or reasons for early withdrawal between the treatment and placebo groups. INTERPRETATION: The long-term combined structure-modifying and symptom-modifying effects of gluosamine sulphate suggest that it could be a disease modifying agent in osteoarthritis. PMID- 11214127 TI - Comparison of formoterol and terbutaline for as-needed treatment of asthma: a randomised trial. AB - BACKGROUND: Asthma guidelines recommend that long-acting inhaled beta-agonists should be used as maintenance therapy for patients with asthma inadequately controlled on an inhaled corticosteroid. We studied the safety and efficacy of the long-acting beta-agonist formoterol compared with terbutaline, each taken as needed, in patients with moderate to severe asthma. METHODS: Patients were taking an inhaled corticosteroid (mean dose 870 microg daily) and had a forced expiratory volume in 1 s (FEV1) of at least 50% predicted (mean 74%). Those requiring an inhaled beta-agonist three to eight times a day during the study run in period (362 of 621 who started) were randomly assigned formoterol 4.5 microg or terbutaline 0.5 mg as needed by Turbuhaler in daily doses up to 54 microg and 6 mg, respectively, for 12 weeks in a double-blind, parallel-group study. Analyses were by intention to treat. FINDINGS: The 362 randomised patients (157 men, 205 women) had a mean age of 47 years. Patients taking formoterol had a longer time to their first severe asthma exacerbation (relative-risk ratio 0.55 [95% CI 0.34-0.89]), took fewer inhalations of study drug, and had larger increases in FEV1 (5%) and morning and evening peak expiratory flow (mean difference in increase 11 L/min and 8 L/min) than those taking terbutaline. No safety issues were identified. INTERPRETATION: When taken as needed, formoterol 4.5 microg provided better asthma control than terbutaline 0.5 mg in patients requiring moderate doses of relief medication despite inhaled corticosteroid treatment. Safety studies should be extended to a wider population of patients with asthma. PMID- 11214128 TI - Colorectal cancer rates among first-degree relatives of patients with inflammatory bowel disease: a population-based cohort study. AB - BACKGROUND: Inflammatory bowel disease (IBD) and colorectal cancer might share a common cause and, therefore, relatives of patients with IBD could be at increased risk of this malignant disease. We aimed to assess cancer rates among first degree relatives of patients with IBD to try to determine whether an association between the two diseases exists. METHODS: In a population-based study, we identified 114,102 first-degree relatives by registry linkage and followed them up for cancer occurrence. We used standardised incidence ratio (SIR) of cancer as relative risk. FINDINGS: 560 colorectal cancers were identified among relatives. First-degree relatives of patients with Crohn's disease or ulcerative colitis were not at increased risk of cancer (SIR 0.90, 95% CI 0.82-0.97). The relative risk was 0.96 (0.87-1.06, n=379) for colon cancer and 0.78 (0.68-0.91, 181) for rectal cancer. The SIRs were not affected by age, relation to patient, or type or extent of IBD in the patient. Relatives of patients with both IBD and colorectal cancer had an 80% increased risk of colorectal cancer. INTERPRETATION: Our results do not endorse a common cause of IBD and colorectal cancer. The slightly decreased relative risk for colorectal cancer among relatives could indicate the proportion of all colorectal cancer cases attributable to IBD. PMID- 11214129 TI - Clinical picture: thrombus in the left atrial appendage. PMID- 11214130 TI - Charcot-Marie-Tooth disease and sleep apnoea syndrome: a family study. AB - BACKGROUND: Charcot-Marie-Tooth (CMT) disease is a genetically heterogeneous group of hereditary motor and sensory polyneuropathies in which sleep apnoea has rarely been reported and no causal relation shown. We looked for an association between the most common subtype of CMT disease (CMT1A) and sleep apnoea syndrome. METHODS: Having diagnosed sleep apnoea and CMT in one family member (index case), we prospectively investigated 13 further members not previously suspected of having neuropathy or apnoeas. All had a neurological examination, electroneuromyography, polysomnography, and genetic testing for CMT disease. FINDINGS: 11 of the 14 family members had the autosomal dominant demyelinating form of CMT disease with PMP22 gene duplication on chromosome 17. Whatever their neurological disability, all 11 individuals had sleep apnoea syndrome with a mean (SD) apnoea-hypopnoea index of 46.6/h (28.5) of sleep (normal value <15/h). The remaining three family members were free from neuropathy and sleep apnoea syndrome. Sleep apnoea and neuropathy severity were highly correlated; the compound muscle action potential (CMAP) amplitude of the median nerve was inversely correlated with the apnoea-hypopnoea index (r=-0.69, p=0.029). The severity of neuropathy and sleep apnoea were higher in male CMT individuals and were correlated with age and body mass index. No wake or sleep diaphragmatic dysfunction was shown. INTERPRETATION: We think that sleep apnoea syndrome is related to a pharyngeal neuropathy. Upper airway dysfunction, previously described in the CMT2C subtype, might be a clinical expression of the CMT1A subtype, to which familial susceptibility could predispose. PMID- 11214131 TI - Quality of life and cost-effectiveness of levonorgestrel-releasing intrauterine system versus hysterectomy for treatment of menorrhagia: a randomised trial. AB - BACKGROUND: Heavy menstrual blood loss is a common reason for women to seek medical care. The levonorgestrel-releasing intrauterine system (IUS) is an effective medical treatment for menorrhagia. We report a randomised comparison of this approach with hysterectomy in terms of the quality of life of women with menorrhagia and cost-effectiveness. METHODS: Of 598 women referred with menorrhagia to five university hospitals in Finland, 236 were eligible and agreed to take part. They were randomly assigned treatment with the levonorgestrel releasing IUS (n=119) or hysterectomy (n=117). The amount of menstrual blood loss was objectively measured. The primary outcome measure was health-related quality of life at 12-month follow-up. Analyses were by intention to treat. FINDINGS: In the group assigned the levonorgestrel-releasing IUS, 24 (20%) women had had hysterectomy and 81 (68%) continued to use the system at 12 months. Of the women assigned to the hysterectomy group, 107 underwent the operation. Health-related quality of life improved significantly in both the IUS and hysterectomy groups (change 0.10 [95% CI 0.06-0.14] in both groups) as did other indices of psychological wellbeing. There were no significant differences between the treatment groups except that women with hysterectomy suffered less pain. Overall costs were about three times higher for the hysterectomy group than for the IUS group. INTERPRETATION: The significant improvement in health-related quality of life highlights the importance of treating menorrhagia. During the first year the levonorgestrel-releasing IUS was a cost-effective alternative to hysterectomy in treatment of this disorder. PMID- 11214132 TI - A confused uraemic woman. PMID- 11214133 TI - Myoblast transplantation for heart failure. AB - Intramyocardial skeletal muscle transplantation has been shown experimentally to improve heart function after infarction. We report success with this procedure in a patient with severe ischaemic heart failure. We implanted autologous skeletal myoblasts into the postinfarction scar during coronary artery bypass grafting of remote myocardial areas. 5 months later, there was evidence of contraction and viability in the grafted scar on echocardiography and positron emission tomography. Although this result is encouraging, it requires validation by additional studies. PMID- 11214135 TI - Hyponatraemia as a complication of colonoscopy. AB - A case of colonoscopy-induced hyponatraemic encephalopathy led us to study the risk of hyponatraemia after gastrointestinal endoscopy. We assessed 40 patients before and after colonoscopy. 20 gastroscopy patients served as controls. Our findings show a high incidence (7.5%) of hyponatraemia after colonoscopy, in association with raised serum concentrations of arginine vasopressin. Physicians should be aware of this complication, since it may contribute to psychological and neurological symptoms after colonoscopy. PMID- 11214134 TI - Increased mitochondrial toxicity with ribavirin in HIV/HCV coinfection. AB - In two of 15 patients coinfected with HIV and hepatitis C virus who received interferon-alpha plus ribavirin in addition to HAART, we observed multiorgan dysfunction and lactic acidaemia. As ribavirin is a nucleoside analogue, an increased risk of mitochondrial toxicity can be induced in HIV-infected patients already treated with nucleoside analogues, leading to clinical deterioration in some cases. PMID- 11214136 TI - Oral mature teratoma containing epididymal tissue in a female neonate. AB - We describe a female neonate with an oral teratoma showing bone, teeth, and epidermis, but also epididymal (male) tissue. PCR amplification of Y-chromosomal DNA clearly showed male DNA from paraffin-embedded tumour tissue. The girl had a normal female karyotype without abnormalities of the genital organs. There are at least three hypotheses for the origin of teratomas: parthenogenesis, incomplete twinning, and totipotent somatic-cell origin. This case supports the hypothesis of an included dizygotic twin, and might contribute to the elucidation of the pathogenesis of extragonadal teratomas. PMID- 11214137 TI - Biocomplexity: look at the whole, not the parts. PMID- 11214138 TI - The doctor who broke rules of engagement with Pyongyang. PMID- 11214139 TI - Prevention fails to halt South Africa's well-treated cholera epidemic. PMID- 11214140 TI - UK starts campaign to reassure parents about MMR-vaccine safety. PMID- 11214141 TI - UK government overhauls nationwide cancer health care. PMID- 11214142 TI - FDA wants more disclosure of gene-therapy and xenotransplantation risks. PMID- 11214143 TI - Uterine fibroids. AB - Uterine leiomyomas (fibroids or myomas), benign tumours of the human uterus, are the single most common indication for hysterectomy. They are clinically apparent in up to 25% of women and cause significant morbidity, including prolonged or heavy menstrual bleeding, pelvic pressure or pain, and, in rare cases, reproductive dysfunction. Thus, both the economic cost and the effect on quality of life are substantial. Surgery has been the mainstay of fibroid treatment, and various minimally invasive procedures have been developed in addition to hysterectomy and abdominal myomectomy. Formation of new leiomyomas after these conservative therapies remains a substantial problem. Although medications that manipulate concentrations of steroid hormones are effective, side-effects limit long-term use. A better approach may be manipulation of the steroid-hormone environment with specific hormone antagonists. There has been little evidence based evaluation of therapy. New research into the basic biology of these neoplasms may add new treatment options for the future as the role of growth factors and genetic mutations in these tumours are better understood. PMID- 11214144 TI - The fourth disease, 1900-2000. AB - Measles and scarlet fever were differentiated from one another in the 17th century. Rubella was accepted as the third distinct paediatric exanthem in 1881. Nil Filatow in 1885 and Clement Dukes in 1894 described two distinct forms of rubella, and in 1900 Dukes proposed that one of these forms of rubella was a separate entity which he called the fourth disease. For the past five decades, fourth disease has been considered a non-entity, perhaps a mild form of scarlet fever, but certainly not a distinct disease. In 1979 Keith Powell resurrected the idea of the fourth disease and argued that it was caused by exotoxin-producing Staphylococcus aureus. We present additional arguments for the existence of fourth disease, as well as information to link the disease to S. aureus. PMID- 11214145 TI - Japan's "comfort women". PMID- 11214146 TI - Supporting local efforts to document human-rights violations in armed conflict. PMID- 11214147 TI - Responding to rape. PMID- 11214148 TI - Sexual violence in Sierra Leone. PMID- 11214149 TI - Breast-conserving surgery. PMID- 11214150 TI - Acute radiation proctitis. PMID- 11214151 TI - Acute radiation proctitis. PMID- 11214152 TI - Human herpesvirus as a sexually transmitted agent. PMID- 11214153 TI - Use of medication in Zanzibar. PMID- 11214154 TI - Adult growth-hormone deficiency. PMID- 11214155 TI - Rats and risk. PMID- 11214156 TI - Prenatal identification of fetal genetic traits. PMID- 11214157 TI - Cause of otitis media. PMID- 11214158 TI - Choroidal abnormalities and mental retardation in neurofibromatosis type 1. PMID- 11214159 TI - Pre-eclampsia. PMID- 11214160 TI - Pre-eclampsia. PMID- 11214161 TI - Care after cure in leprosy. PMID- 11214162 TI - Risk of asthma. PMID- 11214163 TI - Catalase deficiency, diabetes, and mitochondrial function. PMID- 11214164 TI - Changes in trial parameters. PMID- 11214165 TI - Does lung cancer need a lapel ribbon? PMID- 11214166 TI - Does lung cancer need a lapel ribbon? PMID- 11214167 TI - The Joy of health. PMID- 11214168 TI - The Joy of health. PMID- 11214169 TI - The Joy of health. PMID- 11214170 TI - Keats's notebook. PMID- 11214171 TI - Viewing the ribosome and visiting the nucleolus at Lake Tahoe. PMID- 11214172 TI - Tethered-function analysis reveals that elF4E can recruit ribosomes independent of its binding to the cap structure. AB - The cap-binding complex elF4F is involved in ribosome recruitment during the initiation phase of translation and is composed of three subunits: elF4E, -4G, and -4A. The m7GpppN cap-binding subunit eIF4E binds the N-terminal region of eIF4G, which in turn contacts eIF4A through its central and C-terminal regions. We have previously shown, through a tethered-function approach in transfected HeLa cells, that the binding of eIF4G to an mRNA is sufficient to drive productive translation (De Gregorio et al., EMBO J, 1999, 18:4865-4874). Here we exploit this approach to assess which of the other subunits of elF4F can exert this function. eIF4AI or mutant forms of eIF4E were fused to the RNA-binding domain of the lambda phage antiterminator protein N to generate the chimeric proteins lambda4A, lambda4E-102 (abolished cap binding), and lambda4E-73-102 (impaired binding to both, the cap and eIF4G). The fusion proteins were directed to a bicistronic reporter mRNA by means of interaction with a specific lambda-N binding site (boxB) in the intercistronic space. We show that lambda4E-102, but neither the double mutant lambda4E-73-102 nor lambda4A, suffices to promote translation of the downstream gene in this assay. Coimmunoprecipitation analyses confirmed that all lambda-fusion proteins are capable of interacting with the appropriate endogenous eIF4F subunits. These results reveal that eIF4E, as well as eIF4G, can drive ribosome recruitment independent of a physical link to the cap structure. In spite of its interaction with endogenous eIF4G, lambda4A does not display this property. eIF4A thus appears to supply an essential auxiliary function to eIF4F that may require its ability to cycle into and out of this complex. PMID- 11214174 TI - The stem-loop binding protein forms a highly stable and specific complex with the 3' stem-loop of histone mRNAs. AB - Replication-dependent histone mRNAs end in a highly conserved 26-nt stem-loop structure. The stem-loop binding protein (SLBP), an evolutionarily conserved protein with no known homologs, interacts with the stem-loop in both the nucleus and cytoplasm and mediates nuclear-cytoplasmic transport as well as 3'-end processing of the pre-mRNA by the U7 snRNP. Here, we examined the affinity and specificity of the SLBP-RNA interaction. Nitrocellulose filter-binding experiments showed that the apparent equilibrium dissociation constant (Kd) between purified SLBP and the stem-loop RNA is 1.5 nM. Binding studies with a series of stem-loop variants demonstrated that conserved residues in the stem and loop, as well as the 5' and 3' flanking regions, are required for efficient protein recognition. Deletion analysis showed that 3 nt 5' of the stem and 1 nt 3' of the stem contribute to the binding energy. These data reveal that the high affinity complex between SLBP and the RNA involves sequence-specific contacts to the loop and the top of the stem, as well the base of the stem and its immediate flanking sequences. Together, these results suggest a novel mode of protein-RNA recognition that forms the core of a ribonucleoprotein complex central to the regulation of histone gene expression. PMID- 11214173 TI - A novel protein-RNA binding assay: functional interactions of the foot-and-mouth disease virus internal ribosome entry site with cellular proteins. AB - Translation initiation on foot-and-mouth disease virus (FMDV) RNA occurs by a cap independent mechanism directed by a highly structured element (approximately 435 nt) termed an internal ribosome entry site (IRES). A functional assay to identify proteins that bind to the FMDV IRES and are necessary for FMDV IRES-mediated translation initiation has been developed. In vitro-transcribed polyadenylated RNAs corresponding to the whole or part of the FMDV IRES were immobilized on oligo-dT Dynabeads and used to deplete rabbit reticulocyte lysate (RRL) of IRES binding proteins. Translation initiation factors eIF4G, eIF4A, and eIF4B bound to the 3' domain of the FMDV IRES. Depletion of eIF4G from RRL by this region of the FMDV IRES correlated with the loss of translational capacity of the RRL for capped, uncapped, and FMDV IRES-dependent mRNAs. However, this depleted RRL still supported hepatitis C virus IRES-directed translation. Poly (rC) binding protein 2 bound to the central domain of the FMDV IRES, but depletion of RRL with this IRES domain had no effect on FMDV IRES-directed translation initiation. PMID- 11214175 TI - Yeast U1 snRNP-pre-mRNA complex formation without U1snRNA-pre-mRNA base pairing. AB - Base pairing between the 5' end of U1 snRNA and the conserved 5' splice site of pre-mRNA is important for commitment complex formation in vitro. However, the biochemical mechanisms by which pre-mRNA is initially recognized by the splicing machinery is not well understood. To evaluate the role of this base pairing interaction, we truncated U1 snRNA to eliminate the RNA-RNA interaction and surprisingly found that U1 snRNP can still form a nearly normal RNA-protein complex and maintain sequence specificity. We propose that some feature of U1 snRNP, perhaps one or more protein factors, is more important than the base pairing for initial 5' splice site recognition. In addition, at least five sets of interactions contribute to complex formation or stability. Only one of these is base pairing between the 5' splice site and the 5' end of U1 snRNA, without which the U1 snRNP-pre-mRNA complex is less stable and has a somewhat altered conformation. PMID- 11214176 TI - Two alternating structures of the HIV-1 leader RNA. AB - In this study we demonstrate that the HIV-1 leader RNA exists in two alternative conformations, a branched structure consisting of several well-known hairpin motifs and a more stable structure that is formed by extensive long-distance base pairing. The latter conformation was first identified as a compactly folded RNA that migrates unusually fast in nondenaturing gels. The minimally required domains for formation of this conformer were determined by mutational analysis. The poly(A) and DIS regions of the leader are the major determinants of this RNA conformation. Further biochemical characterization of this conformer revealed that both hairpins are disrupted to allow extensive long-distance base pairing. As the DIS hairpin is known to be instrumental for formation of the HIV-1 RNA dimer, the interplay between formation of the conformer and dimerization was addressed. Formation of the conformer and the RNA dimer are mutually exclusive. Consequently, the conformer must rearrange into a branched structure that exposes the dimer initiation signal (DIS) hairpin, thus triggering formation of the RNA dimer. This structural rearrangement is facilitated by the viral nucleocapsid protein NC. We propose that this structural polymorphism of the HIV-1 leader RNA acts as a molecular switch in the viral replication cycle. PMID- 11214177 TI - Replicating satellite RNA induces sequence-specific DNA methylation and truncated transcripts in plants. AB - Tobacco plants were transformed with a chimeric transgene comprising sequences encoding beta-glucuronidase (GUS) and the satellite RNA (satRNA) of cereal yellow dwarf luteovirus. When transgenic plants were infected with potato leafroll luteovirus (PLRV), which replicated the transgene-derived satRNA to a high level, the satellite sequence of the GUS:Sat transgene became densely methylated. Within the satellite region, all 86 cytosines in the upper strand and 73 of the 75 cytosines in the lower strand were either partially or fully methylated. In contrast, very low levels of DNA methylation were detected in the satellite sequence of the transgene in uninfected plants and in the flanking nonsatellite sequences in both infected and uninfected plants. Substantial amounts of truncated GUS:Sat RNA accumulated in the satRNA-replicating plants, and most of the molecules terminated at nucleotides within the first 60 bp of the satellite sequence. Whereas this RNA truncation was associated with high levels of satRNA replication, it appeared to be independent of the levels of DNA methylation in the satellite sequence, suggesting that it is not caused by methylation. All the sequenced GUS:Sat DNA molecules were hypermethylated in plants with replicating satRNA despite the phloem restriction of the helper PLRV. Also, small, sense and antisense approximately 22 nt RNAs, derived from the satRNA, were associated with the replicating satellite. These results suggest that the sequence-specific DNA methylation spread into cells in which no satRNA replication occurred and that this was mediated by the spread of unamplified satRNA and/or its associated 22 nt RNA molecules. PMID- 11214178 TI - A ribozyme selected from variants of U6 snRNA promotes 2',5'-branch formation. AB - In vitro selection was used to sample SnRNA-related sequences for ribozyme activities, and several 2',5'-branch-forming ribozymes were isolated. One such ribozyme is highly dependent upon an 11-nt motif that contains a conserved U6 snRNA sequence (ACAGAGA-box) known to be important for pre-mRNA splicing. The ribozyme reaction is similar to the first step of splicing in that an internal 2' hydroxyl of an unpaired adenosine attacks at the 5'-phosphate of a guanosine. It differs in that the leaving group is diphosphate rather than a 5' exon. The finding that lariat formation can be accomplished by a small RNA with sequences related to U6 snRNA indicates that the RNA available in the spliceosome may be involved in RNA-catalyzed branch formation. PMID- 11214179 TI - Thermodynamics of 2'-ribose substitutions in UUCG tetraloops. AB - The ribose 2'-hydroxyl group confers upon RNA many unique molecular properties. To better appreciate its contribution to structure and stability and to monitor how substitutions of the 2' hydroxyl can alter an RNA molecule, each loop pyrimidine ribonucleotide in the UUCG tetraloop was substituted with a nucleotide containing either a fluorine (2'-F), hydrogen (2'-H), amino (2'-NH2), or methoxy (2'-OCH3) group, in the context of both the C:G and G:C loop-closing base pair. The thermodynamic parameters of these tetraloop variants have been determined and NMR experiments used to monitor the structural changes resulting from the substitutions. The modified riboses are better tolerated in the G[UUCG]C tetraloop, which may be due to its increased loop flexibility relative to the C[UUCG]G loop. Even for these simple substitutions, the free-energy change reflects a complex interplay of hydrogen bonding, solvation effects, and intrinsic pucker preferences of the nucleotides. PMID- 11214180 TI - Evidence that phosphorylation of human Upfl protein varies with intracellular location and is mediated by a wortmannin-sensitive and rapamycin-sensitive PI 3 kinase-related kinase signaling pathway. AB - Human Upf1 protein (p), a group 1 RNA helicase, has recently been shown to function in nonsense-mediated mRNA decay (NMD) in mammalian cells. Here, we demonstrate that the estimated 3 x 10(6) copies of hUpf1 p per exponentially growing HeLa cell are essentially equally distributed among polysomal, subpolysomal, and ribosome-free fractions. We also demonstrate that hUpf1p binds RNA and is a phosphoprotein harboring phosphoserine and phosphothreonine. hUpf1p is phosphorylated to the highest extent when polysome-associated and to the lowest extent when ribosome free. We find that serum-induced phosphorylation of hUpf1p is inhibited by wortmannin at a concentration that selectively inhibits PI 3-kinase related kinases and, to a lesser extent, by rapamycin. These and other data suggest that phosphorylation is mediated by a wortmannin-sensitive and rapamycin-sensitive PI 3-kinase-related kinase signaling pathway. Comparisons are made of hUpf1p to Upf1p and SMG-2, which are the orthologs to hUpf1p in Saccharomyces cerevisiae and Caenorhabditis elegans, respectively. PMID- 11214181 TI - Interactions between 23S rRNA and tRNA in the ribosomal E site. AB - Interactions between tRNA or its analogs and 23S rRNA in the large ribosomal subunit were analyzed by RNA footprinting and by modification-interference selection. In the E site, tRNA protected bases G2112, A2392, and C2394 of 23S rRNA. Truncated tRNA, lacking the anticodon stem-loop, protected A2392 and C2394, but not G2112, and tRNA derivatives with a shortened 3' end protected only G2112, but not A2392 or C2394. Modification interference revealed C2394 as the only accessible nucleotide in 23S rRNA whose modification interferes with binding of tRNA in the large ribosomal subunit E site. The results suggest a direct contact between A76 of tRNA A76 and C2394 of 23S rRNA. Protections at G2112 may reflect interaction of this 23S rRNA region with the tRNA central fold. PMID- 11214182 TI - Functional mapping of ribosome-contact sites in the ribosome recycling factor: a structural view from a tRNA mimic. AB - Ribosome recycling factor (RRF) is required for disassembly of the posttermination complex of the ribosome after release of polypeptides. The crystal structure of RRF resembles a tRNA shape, with an architecturally different flexibility compared with tRNA, but its structure-and-function relationships are unknown. We here found that an RRF variant defective in ribosome binding regains the binding capacity through 20 independent secondary changes occurring in three topologically distinct regions of RRF. Because two of these regions are equivalent to the tip of the anticodon stem and the upper surface of the acceptor stem of tRNA, RRF may interact with the ribosome in a way similar to tRNA, spanning 30S and 50S subunits, to exert its action for splitting the ribosome. PMID- 11214183 TI - Arrangement of the central pseudoknot region of 16S rRNA in the 30S ribosomal subunit determined by site-directed 4-thiouridine crosslinking. AB - The 16S rRNA central pseudoknot region in the 30S ribosomal subunit has been investigated by photocrosslinking from 4-thiouridine (s4U) located in the first 20 nt of the 16S rRNA. RNA fragments (nt 1-20) were made by in vitro transcription to incorporate s4U at every uridine position or were made by chemical synthesis to incorporate s4U into one of the uridine positions at +5, +14, +17, or +20. These were ligated to RNA containing nt 21-1542 of the 16S rRNA sequence and, after gel purification, the ligated RNA was reconstituted into 30S subunits. Long-range intramolecular crosslinks were produced by near-UV irradiation; these were separated by gel electrophoresis and analyzed by reverse transcription reactions. A number of crosslinks are made in each of the constructs, which must reflect the structural flexibility or conformational heterogeneity in this part of the 30S subunit. All of the constructs show crosslinking to the 559-562, 570-571, and 1080-1082 regions; however, other sites are crosslinked specifically from each s4U position. The most distinctive crosslinking sites are: 341-343 and 911-917 for s4U(+5); 903-904 (very strong), 1390-1397, and 1492 for s4U(+14); and 903-904 (moderate) for s4U(+17); in the 1070-1170 region in which there are different patterns for each s4U position. These results indicate that part of the central pseudoknot is in close contact with the decoding region, with helix 27 in the 885-912 interval and with part of domain III RNA. Crosslinking between s4U(+14) and 1395-1397 is consistent with base pairing at U14-A1398. PMID- 11214184 TI - The mechanism of RNA binding to TRAP: initiation and cooperative interactions. AB - The trp RNA-binding Attenuation Protein (TRAP) from Bacillus subtilis is an 11 subunit protein that binds a series of 11 GAG and UAG repeats separated by two to three-spacer nucleosides in trp leader mRNA. The structure of TRAP bound to an RNA containing 11 GAG repeats shows that the RNA wraps around the outside of the protein ring with each GAG interacting with the protein in nearly identical fashion. The only direct hydrogen bond interactions between the protein and the RNA backbone are to the 2'-hydroxyl groups on the third G of each repeat. Replacing all 11 of these guanosines with deoxyriboguanosine eliminates measurable binding to TRAP. In contrast, a single riboguanosine in an otherwise entirely DNA oligonucleotide dramatically stabilizes TRAP binding, and facilitates the interaction of the remaining all-DNA portion with the protein. Studies of TRAP binding to RNAs with between 2 and 11 GAGs, UAGs, AAGs, or CAGs showed that the stability of a TRAP-RNA complex is not directly proportional to the number of repeats in the RNA. These studies also showed that the effect of the identity of the residue in the first position of the triplet, with regard to binding to TRAP, is dependent on the number of repeats in the RNA. Together these data support a model in which TRAP binds to RNA by first forming an initial complex with a small subset of the repeats followed by a cooperative interaction with the remaining triplets. PMID- 11214185 TI - The intramolecular stem-loop structure of U6 snRNA can functionally replace the U6atac snRNA stem-loop. AB - The U6 spliceosomal snRNA forms an intramolecular stem-loop structure during spliceosome assembly that is required for splicing and is proposed to be at or near the catalytic center of the spliceosome. U6atac snRNA, the analog of U6 snRNA used in the U12-dependent splicing of the minor class of spliceosomal introns, contains a similar stem-loop whose structure but not sequence is conserved between humans and plants. To determine if the U6 and U6atac stem-loops are functionally analogous, the stem-loops from human and budding yeast U6 snRNAs were substituted for the U6atac snRNA structure and tested in an in vivo genetic suppression assay. Both chimeric U6/U6atac snRNA constructs were active for splicing in vivo. In contrast, several mutations of the native U6atac stem-loop that either delete putatively unpaired residues or disrupt the putative stem regions were inactive for splicing. Compensatory mutations that are expected to restore base pairing within the stem regions restored splicing activity. However, other mutants that retained base pairing potential were inactive, suggesting that functional groups within the stem regions may contribute to function. These results show that the U6atac snRNA stem-loop structure is required for in vivo splicing within the U12-dependent spliceosome and that its role is likely to be similar to that of the U6 snRNA intramolecular stem-loop. PMID- 11214186 TI - Old and new targets of antibacterial therapy. AB - Currently available antibiotics target bacterial cell wall synthesis, protein synthesis, or DNA replication. Antibiotics that are structurally unrelated sometimes have common targets. Mutations in these common targets frequently give rise to bacteria that are resistant to multiple antibiotics. The impact of these bacteria in clinical situations is increasing whereas development of effective antibiotics for their treatment is not keeping pace. This emerging crisis in clinical care has led to intense efforts in new antibiotic development. Both improvements in currently available classes of antibiotics as well as discovery of completely novel ones are being aggressively sought. In this review, the mechanisms of action of available antibiotics will be discussed with emphasis on newly developed drugs. Also, some of the potential new targets of antibiotic therapy in the future will be highlighted. PMID- 11214187 TI - Optimizing clinical outcomes by the use of pharmokinetic and pharmacodynamic principles. AB - Since the advent of antimicrobial chemotherapy, considerable controversy has existed as to the most appropriate method to administer antibiotics to maximize the killing of microorganisms, while minimizing toxicity to the patient. Over the past decade, data gained from animal models of infection, in vitro pharmacodynamic studies, volunteer studies and human clinical trials have enabled us to establish the best mode of drug administration to achieve these goals. The clinician should be aware that appropriate antibiotic selection and dosing depends on pharmacodynamic concepts where there is an integration of the drug's microbiological activity, pharmacokinetic properties and mode of bacterial killing. PMID- 11214188 TI - Mechanisms of bacterial resistance to antimicrobial agents. AB - The 20th century has been considered the antimicrobial era--whereas the 21st century may well represent the post-antimicrobial era. The reason for this dramatic change, should it come to pass, is the development of bacterial resistance to antimicrobial agents. This emerging resistance is now challenging the clinical utility of many antimicrobial agents such that the chemotherapy of hospitalized patients with serious infections has been compromised. If the problem with resistance is to be successfully dealt with by clinicians, the mechanisms of such resistance must be known and understood. This paper thus reviews the most important mechanisms of resistance as well as some of the most important pathogens having these mechanisms. An understanding of these important microbial resistance mechanisms will help the clinician identify circumstances in which resistance may be a problem as well as evaluating the potential usefulness of an alternate antimicrobial agent against resistant microbes. PMID- 11214189 TI - Available laboratory tests to guide antimicrobial therapy. AB - Physicians are encountering more difficulties in treating and managing patients with infectious diseases due to the continued emergence of single and multi-drug resistant organisms. This emphasizes the need of laboratory tests that are of help in predicting or monitoring response to therapy. Several conventional, special, automated and molecular antimicrobial susceptibility tests are available including the disk diffusion test, determination of the minimal inhibitory concentration, the E test, serum bactericidal titers, and determination of antimicrobial levels in blood. This article addresses these and other antimicrobial tests to update and enlighten the physicians in selecting the most relevant test(s) that will help guiding the therapy of infections caused by different bacterial etiologic agents. PMID- 11214190 TI - Molecular diagnosis of antimicrobial resistance. AB - Advances in molecular technology have helped in better understanding of mechanisms and diagnosis of diseases in many medical fields. Several molecular techniques are available for determining the genotypic drug-resistance and monitoring epidemic spread of a particular antimicrobial resistance gene in a hospital or patient population. The molecular (genotypic) testing has several advantages over conventional (phenotypic) testing in being faster and unambiguous, more accurate, able to detect masked resistance and can serve as a "gold" or "reference" test for detecting antibiotic resistance genes. This article addresses these molecular tests with their application and limitations and provide examples of their use especially in Mycobacterium tuberculosis and methicillin resistant Staphylococcus aureus. PMID- 11214191 TI - Common bacteria whose susceptibility to antimicrobials is no longer predictable. AB - The widespread use of antibiotics has been responsible for the development of numerous problems including the emergence of multidrug resistant bacteria, increased number of nosocomial- and community-acquired infections, less than optimal patient outcome, and increased health care costs. Of equal concern is the emergence of resistance in clinical isolates to antibiotics that were once considered "standard" with predictable in vitro susceptibility patterns. Such resistance has been especially notable in organisms that are commonly encountered in a variety of infections including, Streptococcus pneumoniae, Staphylococcus aureus. Enterococci, Klebsiella pneumoniae, and Escherichia coli. It is important for the clinical microbiology laboratory to provide the practicing clinician with accurate and timely antimicrobial susceptibility information which requires the application of standardized and approved in vitro testing methods. The laboratory also serves as a sentinel by maintaining an active monitoring and surveillance program in which current in vitro susceptibility patterns can be compared with local, regional, and national data bases. PMID- 11214192 TI - The impact of antimicrobial resistance on empiric antibiotic selection and antimicrobial use in clinical practice. AB - The prevalence of antimicrobial resistance may vary dramatically between countries and regions and even among different patient populations and between hospitals in the same community. In light of these variations, physicians in practice must make a clinical judgment about the likely pathogen(s) involved in the infectious process. They should have access to up-to-date data on the antimicrobial resistance pattern of commonly encountered pathogens. Such data should be subdivided and analyzed for isolates from community as opposed to hospitalized patients. The data on intensive care units patients and from special groups of patients, such as those undergoing dialysis, organ transplant recipients, or cancer patients receiving chemotherapy, should also be made available to practicing physicians. When antimicrobial resistance is considered to be probable or highly likely, or if empirical therapy has failed, a concerted effort should be made to make a microbiologic diagnosis which will ultimately reduce the cost, simplify therapy and improve the outcome over treatment that is solely empirically based. PMID- 11214193 TI - Current status and changing trends of antimicrobial resistance in Lebanon. AB - Antimicrobial resistance among microorganisms has been on the rise worldwide including Lebanon. Several surveillance programs have been initiated to monitor the patterns of resistance due to the deleterious consequences on patients management. Thus, knowledge about the local antimicrobial resistance patterns is essential for epidemiologic aspects as well as clinical practice. In this context, the current status and changing trends of antimicrobial resistance in Lebanon are addressed covering the most relevant bacterial, mycobacterial and fungal pathogens. PMID- 11214194 TI - Current status and changing trends of antimicrobial resistance in Saudi Arabia. AB - Due to modern travel and ease of spread of infections, it is desirable to widen knowledge of susceptibility of common bacterial isolates from different parts of the world for optimal clinical management and control programs. Over the past decades, antimicrobial resistance has emerged in all kinds of micro-organisms worldwide including Saudi Arabia. This phenomenon is primarily due to increasing antibiotic use and misuse in humans, animals and agriculture. Additionally, the presence of a large expatriate population and a significant number of visitors to the Kingdom annually for pilgrimage and/or work from all over the world may have also facilitated the importation to Saudi Arabia of drug resistant micro organisms from other countries. Saudi Arabia has witnessed an increase of drug resistant Mycobacterium tuberculosis, Streptococcus pneumoniae, Staphylococcus aureus and some Enterobacteriaceae in the last decade. We describe the status of antimicrobial resistance in Saudi Arabia which is an important focus of antimicrobial resistance for the Gulf Region. PMID- 11214195 TI - Transitional (intravenous to oral) antibiotic therapy. AB - Most clinicians feel the best clinical outcome occurs when patients are treated for serious infections with injections for the entire illness. Unfortunately, this type of prescribing style results in considerable indirect costs such as those involved in increased labor (nursing, pharmacy, intravenous technician time), supplies (needles, syringes, intravenous solutions, administration sets, infusion pumps) and nosocomial bacteremia. It now appears from pharmacodynamic and pharmacoeconomic information that this traditional prescribing behavior should change in the management of many infectious diseases, particularly in those clinically stable patients who can ingest or digest a medication. With the presence of numerous antibiotics with high bioavailability, many infections in such patients can now be successfully treated with an oral agent. This review provides examples of common infections (such as community- and hospital-acquired pneumonias, intra-abdominal infections, urinary tract infections, and skin, soft tissue, and bone infections) in which oral therapy can replace parenteral agents. PMID- 11214196 TI - Antibiotic prophylaxis. AB - The use of antibiotic prophylaxis has long been established to prevent the development of invasive infections. In many settings, it is currently considered to be the standard of care to administer antibiotics prior to surgical procedures. The aim is to decrease the load of organisms at the site of manipulation and therefore minimize the appearance of local as well as distant infection. With the increasing number of antimicrobial agents available on the market, physicians are often faced with a dilemma when trying to decide which agent to use. This review addresses the current recommendations of antimicrobial prophylaxis in surgical procedures, in the prevention of infective endocarditis, as well as the prophylaxis required following exposure to highly infective bacteria. PMID- 11214197 TI - Mycobacteria: treatment approaches and mechanisms of resistance. AB - First-line drugs for tuberculosis treatment include isoniazid, rifampin, ethambutol, streptomycin, and pyrazinamide. Molecular mechanisms for resistance to each of these drugs have been elucidated. In every case, resistance is conferred by mutations in existing genes, not by the acquisition of new genetic material. Drug resistance is a major problem worldwide, but the rates vary widely among countries and within countries. Acquired resistance in previously-treated patients is much more common than primary resistance in patients with no previous treatment. High rates of acquired resistance have been reported from referral centers in Saudi Arabia and Lebanon. Successful TB treatment requires prolonged therapy with at least two active drugs. Directly-observed therapy (DOT) improves success rates and reduces the risk of acquired resistance. TB due to susceptible strains can be cured in over 95% of cases. PMID- 11214198 TI - Treatment of human brucellosis. AB - Human brucellosis is a multisystem disease that may present with a broad spectrum of clinical manifestations. The primary goals of therapy for brucellosis are to improve the symptoms, reduce complications and prevent relapses. The choice of a regimen and duration of antimicrobial therapy should be based on the location of the disease and the underlying conditions. The regimen of choice is a combination therapy with doxycycline for 45 days and streptomycin for 14 days. A second choice consists of a combination of doxycycline and rifampin for 45 days. Children under 8 years old and pregnant women should not be treated with tetracyclines. In children under 8 years old, the preferred regimen is rifampin with cotrimoxazole or gentamicin. Rifampin (900 mg once daily for 6 weeks) is considered the drug of choice for treating brucellosis in pregnant women. Surgery should be considered for patients with endocarditis, cerebral, epidural or splenic abscess or other abscesses, which are resistant to antibiotics. PMID- 11214199 TI - Community-acquired respiratory infections: spectrum of organisms and treatment. AB - The respiratory infections addressed in this paper include otitis media, sinusitis, and community-acquired pneumonia. The morbidity and mortality of respiratory infections are assessed from the American standpoint ; their worldwide significance is even greater. The emphasis is on specific diagnosis. Treatment options vary from country to country. Therapeutic decisions are usually easy once a specific etiologic organism is isolated. Since in many of these common respiratory infections a specific microorganism is not documented and empiric therapy is designed based on past clinical studies, resistance patterns need to be known for each country. PMID- 11214200 TI - Infectious diarrhea: pathogens and treatment. AB - Infectious diarrhea is the most common infectious disease syndrome worldwide resulting in more than five million deaths annually. The greatest morbidity and mortality is seen among children younger than two years of age. A variety of bacterial, viral and parasitic pathogens are responsible for the various syndromes. A combination of host susceptibility and organism virulence factors is responsible for disease. Most episodes of gastroenteritis are self-limited. The hallmark of patient management is strict attention to fluid and electrolyte disturbances. Antimotility agents should be used with caution if at all in children, but may be helpful in adults with travelers' diarrhea. Antimicrobial therapy may shorten the duration of diarrhea in some illnesses, but use is restricted due to emergence of resistance or due to lack of availability in some countries. Newer strategies for prevention include vaccine development. PMID- 11214201 TI - Management of urinary tract infections. AB - Urinary tract infections (UTIs) are commonly encountered in medical practice and range from asymptomatic bacteruria to acute pyelonephritis. Enterobacteriaceae with E. coli being the most prevalent, are responsible for most commonly acquired uncomplicated UTIs and usually respond promptly to oral antibiotics. In contradistinction, more resistant pathogens cause nosocomially acquired infections which often require parenteral antibiotic therapy. Patients with acute bacterial prostatitis, usually caused by Enterobacteriaceae present with a tender prostate gland and respond promptly to antibiotic therapy. Chronic bacterial prostatitis on the other hand, is a subacute infection characterized by recurrent episodes of bacterial UTI where the patient presents with vague symptoms of pelvic pain and voiding problems. Treatment is protracted and may be frustrating. Nonbacterial prostatitis and chronic pelvic pain syndrome produce symptoms similar to those of chronic bacterial prostatitis. Treatment is not well defined due to their uncertain etiologies. Most episodes of catheter associated bacteruria are asymptomatic, where less than 5% will be complicated by bacteremia. The use of systemic antibiotics for treatment or prevention of bacteruria is not recommended, particularly in the geriatric age group, since it helps select for resistant organisms. Prevention thus remains the best option to control it. Few patients without catheters who have asymptomatic bacteruria develop serious complications and therefore routine antimicrobial therapy is not justified with only two exceptions : before urologic surgery and during pregnancy. PMID- 11214202 TI - Loneliness and fear of intimacy among adolescents who were taught not to trust strangers during childhood. AB - This study explored feelings of loneliness and fear of intimacy among adolescents as a function of whether they were taught not to trust strangers during childhood. Eighty college students and their parents completed the Revised UCLA Loneliness Scale, both versions of the Fear of Intimacy Scale (FIS-D and FIS-F), and a background information questionnaire. It was found that students whose parents taught them not to trust strangers during childhood had greater fear of intimacy. Further, females who were taught to distrust strangers also experienced more loneliness than did their male counterparts, as well as females and males who were not taught to distrust strangers. PMID- 11214203 TI - High-risk behavior among gay adolescents: implications for treatment and support. AB - This article contrasts the experiences of most adolescents during social and psychological development with the special challenges faced by those developing an awareness of their homosexuality. Emphasis is placed upon the interplay between societal prejudices and discrimination toward homosexuality and personal development and risk-taking behavior in gay adolescents. The implications of these life stressors for gay adolescents are also discussed in terms of their consequences for mental health policy and treatment. PMID- 11214204 TI - Revisiting the imaginary audience and personal fable constructs of adolescent egocentrism: a conceptual review. AB - Adolescents are thought to believe that others are always watching and evaluating them, and that they are special and unique, labeled the imaginary audience and the personal fable, respectively. These two constructs have been fixtures in textbooks on adolescent development, and have been offered as explanations for self-consciousness and risk-taking. However, their characterization of adolescent social cognition as biased has not been supported empirically, the measures used to assess them lack construct validity, and alternative explanations for both ideation patterns have not been explored. Despite these issues, the imaginary audience and personal fable constructs continue to be considered prototypical representations of social cognitive processes during adolescence. This paper (1) reviews theoretical models of the imaginary audience and the personal fable, and the empirical data pertaining to each model, (2) highlights problems surrounding the two most commonly used measures, and (3) outlines directions for future research, so that a better understanding of the imaginary audience and personal fable, and their roles in adolescent development, may be achieved. PMID- 11214205 TI - Angry adolescents who worry about becoming violent. AB - In the present study, 31 of 89 adolescents responded affirmatively to the following statement: "Sometimes I get so angry that I worry I will become violent." These adolescents (the anger group) were compared with the nonanger group, and several differences were found. The anger group (1) reported less intimacy with parents, received less support from them, and was less close to siblings; (2) had more opposite-sex friends, dated more frequently, and more frequently had a boyfriend or girlfriend; (3) had a lower grade point average; (4) were more depressed; and (5) used marijuana more frequently. Results of a regression analysis revealed that depression and dating were the only significant predictors of anger, explaining 17% of the variance. PMID- 11214206 TI - Adolescent victimization and associated suicidal and violent behaviors. AB - This study examined the relationship between victimization and both suicidal and violent behaviors among 1,569 public high school students in New York State (excluding New York City). They had participated in the 1997 Youth Risk Behavior Survey and, based on their responses, were divided into four groups: no suicidal or violent behavior, suicidal behavior only, violent behavior only, and both suicidal and violent behaviors. Males reported significantly more victimization, less suicidal behavior, and more violent behavior compared with females. Logistic regression analyses indicated that all categories of suicidal/violent behaviors were more frequent among those who had been victimized compared with the nonvictimized, for both males and females. In addition, victimized males were over two times more likely than victimized females to report violent behavior only. Gender differences were not significant for victimized students in two groups, suicidal behavior only and both suicidal and violent behaviors, although the results were in the hypothesized direction for suicidal behavior (e.g., females were more prone to suicidal behavior only). It was concluded that identifying and treating the victims of violence should be an integral component of suicide prevention programs and interventions aimed at reducing interpersonal violence in schools. PMID- 11214207 TI - Punishments adolescents find justified: an examination of altitudes toward delinquency. AB - The purpose of this study was to examine adolescents' attitudes toward delinquency, specifically the degree to which they find norm violations acceptable in various circumstances. A total of 1,914 Dutch youths participated: 1,046 reported having committed no crimes in the past year, 578 reported having committed only nonviolent offenses, and 290 reported having committed both violent and nonviolent offenses. It was hypothesized that, in general, delinquents would prescribe less severe punishments for deviant behavior, irrespective of the circumstances. This hypothesis was rejected. It was found, however, that violent delinquents were significantly more tolerant of violent behavior as compared with nondelinquents, with one important exception: when injury was inflicted on someone they knew, they were as little inclined to excuse the perpetrator as were nondelinquents. Violent delinquents discriminated most strongly between friends and strangers as both victims and perpetrators. PMID- 11214208 TI - The relationship between barriers to birth control use and actual birth control use among Mexican-American adolescents. AB - This study examined the relationship between barriers to using birth control and actual use of birth control among a national sample of Mexican-American adolescents. Participants were either over age 15 or sexually active (regardless of age). They responded to survey items on birth control use. Chi-square analysis and t tests were used to investigate whether barriers to using birth control were related to actual use during first intercourse and most recent sexual intercourse. It was found that nonusers had significantly higher barrier scores compared with users of birth control. The results indicate that attitudes toward birth control are associated with actual birth control use among Mexican-American adolescents. Additionally, males and females may have distinct barriers to using birth control. It was concluded that a better understanding of the sexual attitudes and beliefs associated with birth control is needed in order to improve programs seeking to increase the use of birth control among this rapidly expanding, high-risk population. PMID- 11214209 TI - Knowledge about the deleterious effects of smoking and its relationship to smoking cessation among pregnant adolescents. AB - Smoking cessation among pregnant adolescents remains a complex and unresolved issue. The purpose of this study was to examine adolescents' knowledge of the detrimental effects of smoking on pregnant women and fetuses and its relationship to efforts to quit smoking. The sample consisted of 71 pregnant adolescents, and a three-group randomized intervention design-Teen FreshStart (TFS), Teen FreshStart with buddy (TFSB), and usual care control (UCC)-was used. Instruments included a demographic questionnaire, a smoking history questionnaire, and an 11 item scale measuring knowledge of the effects of smoking during pregnancy. For the entire sample, knowledge scores increased significantly (p = .000) from T1 (preintervention) to T2 (postintervention), and the adolescents who quit smoking had significantly higher knowledge at T2 (p = .028) and greater increases (T1 to T2) in their knowledge (p = .019) than did those who did not quit. Together, the TFS and TFSB groups had significantly higher knowledge at T2 (p = .017) and a significantly greater increase in knowledge from T1 to T2 (p = .005) than did the UCC group. This also held true when the TFS and TFSB groups were examined individually. Each had significantly higher knowledge at T2 (TFS, p = .029; TFSB, p = .008) and a significantly greater increase in knowledge from T1 to T2 (TFS, p = .007; TFSB, p = .009) than did the UCC group. Furthermore, despite the small sample sizes, within-group comparisons showed (a) no significant differences between quitters and nonquitters in the UCC group, (b) significantly higher knowledge at T2 (p = .052) and a trend indicating greater increases in knowledge from T1 to T2 (p = .092) for the quitters compared with the nonquitters in the TFS group, and (c) a trend for adolescents in the TFSB group who quit smoking to have greater increases in knowledge compared with those who did not quit (p = .158). These results indicate the need for continued inquiry into the relationship between pregnant teenagers' health knowledge and decisions to stop smoking. PMID- 11214210 TI - "You have to have somebody watching your back, and if thats God, then thats mighty big": the church's role in the resilience of inner-city youth. AB - This study was designed to explore Freeman's (1986) finding that the institution that made the greatest contribution to male African-American youths' socioeconomic success was the church. Thirty-two African-American, Haitian American, and Latino male and female teenagers--16 drawn from inner-city Protestant churches and 16 comparison teenagers from the same communities-were interviewed. The interviews revealed that churched teenagers were less stressed and less likely to have psychological problems than were teenagers in the comparison group. They also appeared more likely to be living with both biological parents, less likely to have a family member on welfare, and more likely to have a job when compared with the other teenagers. They described the church as being central to their lives and as having multiple functions, many of which have been identified in the resilience literature as contributing to positive developmental outcomes. Results are interpreted in light of the transactional model, and recommendations are made, such as expanding the role of the church within these ethnic communities. PMID- 11214211 TI - Fathering and children's sex role orientation in Korea. AB - The purpose of this exploratory study was to examine variation in aspects of contemporary Korean fathering, such as warmth and involvement (frequency and task share), and its relationship to children's sex role development. One hundred and twenty-nine Korean families (fathers, mothers, and their 11- to 13-year-old children) completed standardized questionnaires addressing child-rearing practices, parental involvement, spousal support, and sex role orientations. Statistical analyses of the data revealed that warmth of fathering and father involvement (frequency and task share) were not significantly associated with children's sex role orientations. However, girls' femininity was significantly related to fathers' masculinity. PMID- 11214212 TI - Fitting in: exploring the emotional dimension of adolescent peer pressure. AB - The general public and academic researchers alike have long recognized the importance of peer relations in the lives of young people. However, three issues are notably absent from the dominant models of peer influence. First, these models neglect the affective dimension of a youth's experiences. Second, the models tend to ascribe a passive role to the youth, a stance also reflected methodologically by the absence of the youth's voice. Third, the motivational component remains unspecified; that is, why does a youth conform to peer influence? Using a framework drawn from recent social psychological work on shame and related feelings, the present study collected qualitative data from twelve college students. The findings indicate that negative emotions play a role in peer influence, particularly feelings of inadequacy and isolation, as well as feeling ridiculed, all of which may be indicative of shame. Thus, shame-related feelings may be instrumental in motivating individuals to conform. A variety of directions for future research are suggested. PMID- 11214213 TI - What every professional who works with adolescents needs to know about firesetters. AB - The number of adolescent firesetters has been growing each year, along with the psychological and financial damage they create. It is therefore essential that mental health professionals who work with adolescents be aware of the characteristics of firesetters. This study describes the individual and environmental factors that relate to the etiology and levels of firesetting. Specifically, it discusses different types of firesetters and their aggressive tendencies, internalizing problems, family dynamics, and sociability. Further, it explores the treatment of adolescent firesetters. PMID- 11214214 TI - Interpersonal relationship quality in young adulthood: a gender analysis. AB - This study explored gender differences in the degree to which parent-child dyads and family system variables are associated with relationship quality in late adolescence and early adulthood. It was hypothesized that the quality of mother child and father-child relationships, as well as family adaptability and family cohesion, would be positively correlated with the quality of intimate relationships in late adolescence and young adulthood. Further, it was hypothesized that correlations would vary according to gender. The sample was composed of 50 males and 48 females between the ages of 18 and 24. The results indicated that the relationship of family factors to the intimate relationships of young adults was similar for males and females. Specifically, a positive relationship with mother and greater adaptability in the family system during adolescence were related to more positive intimate relationships in young adulthood. PMID- 11214215 TI - Understanding dysfunctional and functional family behaviors for the at-risk adolescent. AB - At-risk adolescents and their impact on families and society, as well as characteristics of both healthy and maladaptive families, are discussed. Cognitive distortions of dysfunctional adolescents and their effect on family members, along with methods for intervention and creating more healthy environments, are delineated from a systemic viewpoint. PMID- 11214216 TI - Moderate involvement in sports is related to lower depression levels among adolescents. AB - Sports involvement has been found to be related to social and psychological well being in Icelandic adolescents. The present study investigated whether similar relationships exist for American adolescents. A group of 89 high school seniors completed a questionnaire that gathered data on sports involvement, depression, intimacy with parents and friends, and grade point average. It was found that the moderate sports involvement group (3 to 6 hours per week) had lower depression scores than did the low sports involvement group (2 hours or less per week). The findings are discussed. PMID- 11214217 TI - Adolescent sex and mass media: a developmental approach. AB - Media critics point to adolescents' exposure to "sexy" television and popular music. Developmental transitions lead to increased information seeking, and developmental tasks force adolescents to find information sources other than their parents, implying a link between sexy media and adolescent development. Media research informed by knowledge of adolescent development may be able to clarify this connection, and model development is discussed here. PMID- 11214218 TI - Elevated plasma factor VIII levels--a novel risk factor for venous thromboembolism. AB - An association between elevated plasma levels of FVIII:C and arterial thrombosis was first described 20 years ago. More recently a growing literature has centered on the potential role for elevated FVIII:C in venous thromboembolic disease. 25% of patients have plasma FVIII:C levels greater than 1500 IU/l six months following venous thrombosis. This increased FVIII:C appears unrelated to any ongoing acute phase reaction, and reflects a true increase in circulating FVIII protein. Furthermore the increase in FVIII:C is sustained in the vast majority of subjects for years following the thrombotic episode. Multivariate analysis of the Leiden thrombophilia study has demonstrated that increased FVIII is an independent risk factor for venous thromboembolism. Individuals with FVIII:C exceeding 1500 IU/l had a six-fold increased risk, compared to those with FVIII:C levels less than 1000 IU/l. Also, prospective follow-up has shown that patients with high FVIII:C levels are at increased risk for episodes of recurrent venous thrombosis. These findings support the theory that increased plasma levels of FVIII:C represent a constitutional prothrombotic tendency. However the mechanism underlying the elevation in FVIII remains unknown. PMID- 11214219 TI - Recombinant single chain cardiac troponin I-C polypeptides: superior calibration and control materials for cardiac troponin I immunoassays. AB - There has been a need to create stable and reproducible calibration and control materials for cardiac troponin I assays. Free troponin I, native or recombinant, has been known to be unstable, while troponin CI complex can be easily dissociated in low concentrations or in the presence of chelating agents. In order to overcome these difficulties, two single chain troponin I-C polypeptides have been engineered and expressed separately in Escherichia coli. One consists of a full-length of human cardiac troponin I and C, termed as ScTnI-C and the other consists of a stable fragment (aa28-110) of human cardiac troponin I and a full-length troponin C, termed as ScTnI-C-2. Both ScTnI-C and ScTnI-C-2 were purified to homogeneity by affinity chromatography using anti-cTnI monoclonal antibodies. ScTnI-C and ScTnI-C-2 have apparent molecular weights of 45 kD and 30 kD by SDS-PAGE, respectively. Stability studies by Stratus showed that ScTn I-C and ScTnI-C-2 were stable for 4 months at 2-8 degrees C and at least one year at 20 degrees C. When incubated in human serum at 37 degrees C, ScTnI-C-2 was more resistant to proteolysis than ScTnI-C. ScTnI-C can be recognized by all commercial TnI immunoassays with excellent activity. ScTnI-C-2 can be recognized by all immunoassays that target the stable region of cardiac troponin I. Judging by their performances, ScTnI-C and ScTnI-C-2 are both superior materials to be used as calibrators and controls in clinical laboratories. PMID- 11214220 TI - B-type natriuretic peptide (BNP)--validation of an immediate response assay. AB - B-type natriuretic peptide, a proteohormone secreted by the left ventricle in response to wall-tension, is a promising laboratory parameter for the detection and follow-up of heart failure. In this report analytical validation data of a non-isotopic point-of-care testing system for the quantitative determination of BNP (Triage BNP, Biosite, USA) are given. Despite a very short turn-around time of about 10 minutes the assay proved to be reproducible (interassay coefficient of variation (n=10) of 8.4% and 8.0% at concentrations of 19.3 ng/l and 392 ng/l, respectively), linear (r=0.998, from 5 ng/l to 818 ng/l), and rugged with respect to common interferents; compared to the widely used SHIONORIA BNP assay (CIS, France) higher results were found (Triage-BNP = 1.52 x SHIONORIA BNP - 7.0 ng/l; n=70) with a relatively close correlation of the results (r=0.935). It is concluded that the Triage BNP assay meets the analytical requirements for further clinical validation and may allow a more widespread clinical use of BNP determination in contrast to competing assays with long turn-around times. PMID- 11214221 TI - Evaluation of the Dade Behring Dimension RxL clinical chemistry analyzer. AB - The performance of the Dade Behring Dimension RxL clinical chemistry analyzer was evaluated according to the guidelines of the European Committee for Clinical Laboratory Standards. The following analytes were tested: glucose, urea, creatinine, albumin, phosphorus, cholesterol, triglyceride, uric acid, magnesium, sodium, potassium, chloride, calcium, iron and total bilirubin. The Dade Behring Dimension RxL was compared with the Hitachi 704, Bayer RA-1000, Ektachem 250 and Chiron 865 depending on available tests on these analyzers. Coefficients of correlation showed high correlation between compared analyzers. Other performances (intra- and inter-assay variation, carry-over and interferences) of the analyzer were satisfactory. PMID- 11214222 TI - Serodiagnosis of Lyme borreliosis using detection of different immunoglobulin (sub)classes by enzyme-linked immunosorbent assay and Western blotting. AB - To improve the performance of enzyme-linked immunosorbent assays for the serodiagnosis of Lyme borreliosis, the prevalence of several immunoglobulin classes and subclasses against various antigens of Borrelia burgdorferi was investigated by Western blotting. The sera of 40 early Lyme borreliosis patients (ELB), 27 late Lyme borreliosis patients (LLB), 62 healthy controls and 140 non Lyme borreliosis patients were used. Detection of IgG1 versus total IgG was found to be more sensitive in detecting Borrelia burgdorferi antigens, especially flagellin (41 kD) protein, but did not improve the performance of Western blotting. The use of IgG1 detection showed an increase in sensitivity and specificity for the early Lyme borreliosis patient group compared to the standard IgG and IgM detection method by enzyme immunoassays using purified Borrelia burgdorferi flagellum. However, in an enzyme immunoassay using a total sonicate, sensitivity in detecting early Lyme borreliosis and late Lyme borreliosis with IgG1 remained lower compared to the detection of early Lyme borreliosis by IgM antibodies and late Lyme borreliosis by total IgG antibodies. PMID- 11214223 TI - Hepatitis B--an important public health issue. AB - Hepatitis B is one of the most common infectious diseases in the world. It has been estimated that 350 million people worldwide are chronic hepatitis B virus (HBV) carriers. The global prevalence of chronic HBV infection varies widely, from high ( > 8%, e.g., Africa, Asia and the Western Pacific) to intermediate (2 7% e.g., Southern and Eastern Europe) and low (< 2%, e.g., Western Europe, North America and Australia). The predominant routes of transmission vary according to the endemicity of the HBV infection. In areas of high endemicity, perinatal transmission is the main route of transmission, whereas in areas of low endemicity, sexual contact amongst high-risk adults is predominant. Between one third and one-quarter of people infected chronically with HBV are expected to develop progressive liver disease (including cirrhosis and primary liver cancer). Although mass vaccination programs have begun to control the spread of HBV infection, therapeutic intervention is the only option for those with established chronic HBV-associated liver disease. Until recently, the only treatment for chronic hepatitis B was the immune modulator, interferon (IFN) alpha. However, IFN alpha treatment has several disadvantages; it is expensive, it must be administered by injection, there are side-effects, and IFN alpha is poorly tolerated. Lamivudine, a nucleoside analogue, is the first effective, and well tolerated, oral treatment for chronic hepatitis B. In conclusion, although we are still some way from eradicating or curing chronic hepatitis B, the advent of lamivudine allows new populations to benefit from therapy and helps to address the global public health problem of hepatitis B. PMID- 11214224 TI - Changing clinicians' laboratory test requesting behaviour: can the poacher turn gamekeeper? AB - A major reason for the dramatic increase in laboratory costs is the increased number of laboratory investigations, many of which are perceived to be a waste of time and money. In consequence, several strategies, reviewed below, for curtailing clinicians' laboratory usage have been proposed but none has been universally successful. It is clear, however, that a combination of several strategies is likely to be more successful than any single approach. There may be several reasons why no single strategy has been widely adopted in routine practice. We suggest that modern computers have the ability to overcome these obstacles. We propose, therefore, that expert systems at the clinical-laboratory interface utilising a multifactorial approach within a framework of commitment from clinicians and laboratorians offer the best prospect for reducing inappropriate laboratory usage. PMID- 11214225 TI - Hypercalcemia of malignancy--new insights into an old syndrome. AB - Hypercalcemia is a common paraneoplastic syndrome. Tumors induce hypercalcemia by a local mechanism associated with the tumor's production of various cytokines increasing bone osteolysis. In addition, many tumors release humoral factors, mainly parathyroid hormone (PTH)-related protein (PTHrP), which stimulates bone resorption and/or tubular calcium reabsorption leading to hypercalcemia. Interaction of PTHrP with other tumor-elaborated cytokines might explain some nonPTH-like features associated with the hypercalcemia of malignancy syndrome. Using assays recognizing various PTHrP epitopes, the majority of hypercalcemic cancer patients have higher immunoreactive PTHrP levels in either plasma or urine than normal subjects. Present data support the concept that PTHrP might also be a factor which promotes tumor growth and also the development of osteolytic metastasis. A variety of therapeutic approaches are available to lower serum calcium in hypercalcemic cancer patients. The pathophysiological mechanisms of hypercalcemia appear to be a determinant of the efficacy of different antihypercalcemic treatments. PMID- 11214226 TI - Reference ranges for analytes in extravascular body fluids. AB - Interpreting analytes measured in extravascular body fluids can be problematic as the only suitable literature reference, the Geigy Scientific Tables (1), is almost 20 years old, dating back to the year 1981. It is not always possible to apply the values indicated therein to modern analytical procedures since many of these determinations were developed in the 1940es, 1950es and 1960es and measured with methods that have since lost their significance. We therefore did some extensive literature searches to compile an updated list for the most essential extravascular body fluids. The number of analytes featured in the list has been limited to the most relevant substances. A critical examination of the published data revealed that only 10-20% of the papers could actually be used because of insufficient statistical data, too small number of test subjects, or a lack of plausibility. PMID- 11214227 TI - The DSL analog free testosterone assay: serum levels are not related to sex hormone-binding globulin in normative data throughout childhood and adolescence. AB - In this study we tested the performance of easy-to-use and rapid, commercially available immunoassays to measure free testosterone (fT) and sex hormone-binding globulin (SHBG). We asked whether fT and SHBG serum levels are age-dependent and whether or not there is a gender dependence of fT and SHBG in this age group. Finally, by measuring fT and SHBG in sera of a cohort of healthy children and adolescents using commercially available immunoassays, we established normative data for fT and SHBG in this age group: in boys fT levels increased significantly (r=0.83, p<0.0001) from 0.63 pmol/l (median) in the age group below 5 years to 56.9 pmol/l in the age group 16-20 years. In girls fT levels also increased with age (r=0.66, p<0.0001): from 0.72 pmol/l (median) in the age group below 5 years to 3.34 pmol/l in the age group 16-20 years. In contrast, SHBG serum concentrations significantly decreased with age in boys (r=-0.62, p<0.0001) but remained constant in girls (r=0.04, n.s.). Importantly, fT values were independent of SHBG levels as determined by our methods. In conclusion, fT can be measured in an acceptable quality using the DSL analog tracer-based immunoassay and normative data are now available. In addition, SHBG levels in healthy children and adolescents are also given and may permit for studies of pathophysiologic states in this age group. PMID- 11214228 TI - Improved methods for the quantification of free and linked spacer in conjugate vaccine process. AB - In polysaccharide (PS)-protein conjugate vaccine process, indirect coupling via derivatization of the antigenic PS by diamino spacer molecules is widely used. Such a conjugation technology requires the accurate determination of both the degree of PS-amino substitution (linked spacer) and the removal of residual unlinked (free) diamino spacer. We report two methods for the microdetermination of the spacer primary amino groups, based on their fluorescent labelling. In the first developed assay, activated PS is derivatized with 6-aminoquinolyl-N hydroxysuccinimidyl carbamate (AQC) and the free spacer is separated and detected as its AQC derivative by RP-HPLC with fluorescence detection (lambda(Ex,Em) 246/396 nm). In the second assay, activated PS is derivatized with 3-(2 furoyl)quinoline-2-carboxaldehyde (FQ) and its FQ derivative is separated by capillary zone electrophoresis (CZE) with laser-induced-fluorescence (LIF) detection (lambda(Ex/Em) 488/590 nm). Compared to the traditional gel filtration and colorimetric assays, these two methods show major advances in terms of sensitivity, reduced analysis time and small sample requirements. PMID- 11214229 TI - Simultaneous evaluation of molecular size and antigenic stability of PNEUMOVAX 23, a multivalent pneumococcal polysaccharide vaccine. AB - A technique using high performance size exclusion chromatography (HPSEC) with rate nephelometry (RN) detection has been developed to simultaneously measure the relative molecular size and antigenicity of the bacterial polysaccharide components in a multivalent pneumococcal vaccine, PNEUMOVAX 23. This assay was used to establish stability profiles for each of the 23 pneumococcal polysaccharide serotypes in this vaccine formulation, based on concurrent analyses of vaccine lots up to nine years of age. The exceptional inter-assay precision (<1% RSD) permitted detailed analysis of the data and a more accurate measure of the stability of this product that heretofore has not been available. While 21 of the 23 serotypes in the vaccine show essentially no change in molecular size over several years, serotypes 19A and 19F show changes in relative molecular size of approximately 2% per year. Similar decreases in relative molecular size for serotypes 19A and 19F stored in aqueous formulation have also been observed in other commercially available pneumococcal vaccine products. Additionally, stability profiles of relative antigenicity for nine of the 23 serotypes are reported based on information that is simultaneously obtained in the HPSEC/RN analysis. Of the nine serotypes examined, only serotypes 1, 9V and 18C demonstrate antigenic lability over time, in each case showing a decrease in antigenicity on the order of 5% to 10% per year. Overall, this method is a precise and efficient means of providing data on relative molecular size and relative antigenicity for each polysaccharide component of a multivalent vaccine product. Application of this method in stability studies of such vaccines provides critical information for evaluating time-dependent changes in these products. PMID- 11214230 TI - Characterization of multivalent pneumococcal conjugate vaccines. AB - A new heptavalent pneumococcal conjugate vaccine, designed to protect against disease due to serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F, was formulated with aluminium phosphate adjuvant and analysed before testing in infants. Analyses were complicated by the presence of the adjuvant, and by the low level of each antigen; for example, all serotypes were formulated at 2 microg of saccharide /dose (except 6B which was formulated at 4 microg). Type specific analyses were performed on the formulated vaccine, and included determination of immunogenicity and antigenicity; the former was measured by ELISA following immunization of rabbits, the latter was measured by rate nephelometry. Non serotype specific information was also collected, and included total and adsorbed saccharide (by Anthrone assay), and total and adsorbed protein (by Lowry assay). These preclinical data supported the use of the vaccine in infants in a large randomized double-blinded clinical trial in a multiethnic population. The results of this trial show that the vaccine is safe and efficacious. Collectively, the data will be used to support licensure of the heptavalent vaccine, and documents successful scale-up of the formulation process to manufacturing level. PMID- 11214231 TI - Spectroscopic studies of the structure and stability of glycoconjugate vaccines. PMID- 11214232 TI - Monitoring stability of meningococcal group C conjugate vaccines; correlation of physico-chemical methods and immunogenicity assays. AB - Two meningococcal C-CRM197 conjugates differing in oligosaccharide chain length, number of conjugation sites, conjugation chemistry and process were monitored for stability at various temperatures or after repeated freeze-thawing by physico chemical assays. The results were compared with assessment of immunogenicity in mice, previously shown to correlate with performance of the vaccine in clinical trials. The structural stability of the oligosaccharide chains and the protein carrier varied between the two types of conjugates. Neither was adversely affected by repeated freeze-thawing but one developed conformational changes in the protein carrier, detected by optical (CD, fluorescence) and NMR spectroscopy, when incubated at 23 degrees C or above, although integrity of the oligosaccharide structure was maintained. This was not associated with any reduction in primary IgM or IgG antibody responses to meningococcal C polysaccharide. Exposure to more extreme conditions resulting in release of a substantial proportion of free saccharide from the other conjugate sample was accompanied by significant reduction in both IgG and IgM antibody responses. In conclusion, FPLC-SEC, HPAEC-PAD and NMR spectroscopy were found useful for monitoring the stability of meningococcal C-CRM197 conjugates. Although optical spectroscopy was a sensitive method for detecting modification of the protein carrier, the results did not correlate with reduced immunogenicity. PMID- 11214233 TI - Structure activity studies on group C meningococcal polysaccharide-protein conjugate vaccines: effect of O-acetylation on the nature of the protective epitope. AB - A series of group C meningococcal polysaccharide-tetanus toxoid (GCMP-TT) conjugates were prepared as vaccines with varying percentages of O-acetylation at the C-7 and C-8 positions of sialic acid residues in the polysaccharide (PS). The immune response in mice was highly dependent on the degree of O-acetylation. Less O-acetylation resulted in higher serum bactericidal activity (SBA) towards the O acetylated (OA) meningococcal strain, C11. In addition, since an unconjugated de O-acetylated (dOA) GCMP vaccine was previously shown to be highly immunogenic in humans, we had chosen this dOA form to couple with TT by reductive amination for clinical evaluation. This conjugate vaccine was shown to be well-tolerated and highly immunogenic in adults, children, and infants in the UK. To understand the nature of the GCMP protective epitope, a series of spectroscopic and serological studies were conducted, using high resolution H-NMR spectroscopy at 500 MHz and competitive inhibition SBA assays. The dOA GCMP was 10-1000 times better at inhibiting the SBA for an OA strain than the OA GCMP, suggesting that the GCMP based protective epitope on the bacterium exists in a dOA form. In addition, SBA for an OA strain is highly correlated with dOA GCMP-specific IgG. NMR data on freshly isolated GCMP indicated that, on the surface of the organism, most of the O-acetylation exists at position C-8, with some regions containing dOA or OA C-7 sialic acid. After extraction of PS and storage in solution, most of the O-acetyl groups migrate to C-7, leaving an epitope that is conformationally related, but not quite identical (due to the presence of the O-acetyl group), to the one contained in the dOA PS. We speculate that the role of the O-acetyl group at the C-8 position of the PS on the organism is to form less immunogenic epitopes, or mask the protective epitope, and thus escape immune surveillance. The dOA form of the vaccine may therefore provide better protection against group C meningococcal disease than the OA form by eliciting a greater proportion of functional antibodies that are directly aimed at the protective epitope. PMID- 11214234 TI - Characterization of a recombinant outer surface protein A (OspA) vaccine against Lyme disease. AB - Lyme disease, the most prevalent tick-borne disease in the United States, results from infection with Borrelia burgdorferi sensu stricto. Early studies of Borrelia burgdorferi sensu stricto identified outer surface protein A (OspA), a lipoprotein on the surface of spirochetes that could be the target of protective antibodies to this agent. Pasteur Merieux Connaught has developed a Lyme vaccine, ImuLyme, using recombinant OspA protein (rOspA). Methods were developed to routinely assess the identity, quantity, structure, purity, biological activity, heterogeneity, stability, and potency of rOspA. In addition, several methods were performed on a series of lots to support the routine testing methods and further our understanding of the physicochemical characteristics of rOspA. These tests were electrospray mass spectrometry, circular dichroism, two-dimensional gel electrophoresis, amino acid analysis, peptide mapping with peptide sequencing, and the application of proteomic methodology to identify trace contaminant host cell proteins. The results of these methods indicate that the rOspA lots are composed of highly purified and properly processed and folded rOspA with trace amounts of E. coli host cell proteins. PMID- 11214235 TI - Physicochemical characterisation of the pertussis vaccine. AB - The characterisation of an acellular pertussis vaccine composed of a genetically modified pertussis toxin, filamentous haemagglutinin and pertactin is described. The three antigens are submitted to a mild treatment with formaldehyde in the presence of lysine before their use in vaccine formulation. Characterisation is performed by amino acid analysis, SDS-PAGE, analytical size exclusion chromatography and, in the case of pertactin, isoelectrofocusing. The effect of some variables on pertactin formaldehyde treatment has been studied by means of isoelectrofocusing and mouse immunogenicity. PMID- 11214236 TI - Biophysical validation of Epaxal Berna, a hepatitis A vaccine adjuvanted with immunopotentiating reconstituted influenza virosomes (IRIV). AB - Inactivated vaccines usually contain an adjuvant which potentiates the immune response to the antigen. During the last 70 years aluminium salts have been the only adjuvant licensed for human use. The adjuvanting activity is based on their serving as an antigen depot and inducing a localized inflammatory response. Our efforts to develop a potent and well tolerated adjuvant has focussed on the use of immunopotentiating reconstituted influenza virosomes (IRIV). The IRIV base is a liposome with a mean diameter of 150 nm, comprising phosphatidylcholine (PC) and phosphatidylethanolamine (PE). These mammalian phospholipids are virtually non-immunogenic and have enjoyed a long history of use in human pharmaceutical preparations. The haemagglutinin (HA) and trace quantities of viral neuraminidase and phospholipids from the A/Singapore 6/86 virus strain are intercalated within the phospholipid bilayer. The presence of the HA is necessary to enhance the immunopotentiating effect to antigen associated with IRIV The excellent characteristics of IRIVs as adjuvants have been demonstrated in several systems. IRIVs as alternative adjuvant system for human use are registered by most European, Asian and American countries in commercial hepatitis A and influenza vaccines. IRIVs were first used in the manufacture of a hepatitis A vaccine. This contains formalin-inactivated and highly purified hepatitis A virus (HAV) of strain RG-SB, cultured in human diploid cells, which is coupled to the IRIV vesicle. For a new influenza vaccine the surface spikes (HA and NA) of three currently circulating influenza strains were jointly inserted into the vesicle membrane of the IRIVs and successfully tested clinically. In Epaxal Berna, the first commercially available liposomal vaccine is expected to be the inactivated hepatitis A virus adsorbed to IRIV particles. In the virosomal hepatitis A vaccine, the antigen is believed to be attached to the IRIV by interacting with phospholipids which are considered to correspond to its natural receptor on hepatocytes. The present investigation includes data based on light scattering measurements which show the binding of the virions to vesicles. PMID- 11214237 TI - Properties of recombinant HtrA: an otitis media vaccine candidate antigen from non-typeable Haemophilus influenzae. AB - Non-encapsulated or non-typable Haemophilus influenzae (NTHi) is a major cause of middle ear infections in young children. HtrA has been identified as a vaccine candidate antigen from NTHi; therefore physicochemical characterization of this antigen is important for vaccine development. Recombinant NTHi HtrA has been expressed in E. coli and shown to have serine protease activity. Several mutant, recombinant HtrA proteins were expressed and purified to obtain suitable vaccine antigens lacking protease activity. Two mutants with alterations at the putative active site His91 and Ser197, designated H91A and S197A were examined by circular dichroic spectropolarimetry (CD) to evaluate secondary structure. The S197A mutant had a more random secondary structure compared to wild-type rHtrA or H91A. It is likely that improper folding of S197A accounts for its lack of immunoprotective properties in a chinchilla model of otitis media. PMID- 11214238 TI - Physicochemical analysis of purified diphtheria toxoids: is toxoided then purified the same as purified then toxoided? AB - Diphtheria toxin can be converted into a highly immunogenic and irreversibly detoxified vaccine either using the conventional process in which the crude toxin is formalinised and subsequently purified (DTxd(conv)) or by detoxification of the highly purified toxin (DTxd(new)). In this study, both DTxd(new) and DTxd(conv) were evaluated by use of physico-chemical methods. For some methods, results were also compared to those obtained for cross-reacting material (CRM197), which is a non-toxic mutant of diphtheria toxin. DTxd(new) was assayed to have a specific purity of at least 2300 LF/mg protein N, thereby exceeding Pharm. Eur. requirements by up to 35%. Superior purity of DTxd(new) could also be demonstrated by size exclusion HPLC experiments and by amino acid composition studies. Far-UV circular dichroism spectroscopy revealed that the secondary structure of DTxd(new) almost resembled that of CRM197, suggesting only minor molecular changes during detoxification. This study worked out differences between purified diphtheria toxoids. Physico-chemical means revealed the advantages of DTxd(new) being the purer and more defined product, thus making it highly efficient for its use as a vaccine carrier as well as a component of vaccine combinations. PMID- 11214239 TI - Characterization of aluminium-containing adjuvants. AB - The approved aluminium-containing vaccine adjuvants have been shown to be poorly crystalline aluminium oxyhydroxide (AIO(OH)) and amorphous aluminium hydroxyphosphate of varying phosphate content. Adsorption of the antigen by the adjuvant is implied in many proposed mechanisms of antibody production enhancement caused by the adjuvants. The World Health Organization recommends adsorption of 80% or more of tetanus and diphtheria toxoid by the aluminium containing adjuvants. Thus, one objective in the preparation of vaccines containing these adjuvants is to optimize adsorption of the antigen on the adjuvant. Production of a consistent adjuvant effect in vaccines would be facilitated by the thorough characterization of aluminium-containing adjuvants with reference to properties that affect adsorption and other colloidal behaviour. Such properties include surface area, surface charge, chemical composition, structure, and morphology. Techniques and measurements such as X-ray diffraction, infrared spectroscopy, transmission electron microscopy, energy dispersive spectrometry, Doppler electrophoretic light scattering analysis, dissolution rates, and adsorption isotherms provide a basis for understanding and predicting interactions and behaviour in monovalent as well as multivalent vaccines. Such characterization would be crucial in vaccine standardization and quality control. PMID- 11214240 TI - Synthesis and characterization of respiratory syncytial virus protein G related peptides containing two disulphide bridges. AB - Respiratory Syncytial Virus (RSV) is the most important cause of bronchiolitis and viral pneumoniae in infants and young children. Approximately 100,000 children are hospitalized in the USA each year as a result of RSV infections. During the research and development of subunit human RSV vaccines, we have produced numerous synthetic peptides and recombinant proteins containing the four cysteines of the highly conserved central region of the G attachment protein. For several of these disulphide bridges containing peptides, all possible oxidizing isomers were synthesized using various oxidising conditions, resulting in different ratios of isomers. Each isolated isomer was fully characterized by RP HPLC, FZCE and ES-MS after purification by preparative RP-HPLC. The different cysteine pairings were unambiguously established after enzymatic digestion, LC-MS analysis and peptide microsequencing. These synthetic and analytical methods were developed for the characterization of recombinant fusion protein BBG2Na which is currently investigated in clinical phase II and seems to be as a very promising vaccine candidate, and for peptides which were synthesized to be evaluated as conjugate vaccines or as immunochemical tools, after covalent coupling to carrier proteins. Furthermore, these studies allowed us to determine which of the different possible isomers was the most stable and probably the preferred form in native conditions. Finally, the different oxidising and analysis conditions, should be useful for disulphide pairing studies of other peptides and proteins having the same "xCxxCxxxxxCxxxCx" framework, such as G proteins of non-human RSV strains, developed for example as veterinary vaccine candidates. PMID- 11214241 TI - Direct biophysical characterization of protein antigens in ISCOM formulations. PMID- 11214242 TI - Absolute molecular-size and molar-mass analysis of meningococcal and pneumococcal conjugates and polysaccharide intermediates by size-exclusion chromatography with detection by multiangle light-scattering photometry and differential refractometry. PMID- 11214243 TI - Measurement of kinetic binding constants of pneumococcal polysaccharide antibodies using plasmon surface resonance. PMID- 11214244 TI - Physico-chemical characterization and immunogenicity studies of peptide and polysaccharide conjugate vaccines based on a promising new carrier protein, the recombinant Klebsiella pneumoniae OmpA. PMID- 11214245 TI - Capillary electrophoretic analysis of meningococcal polysaccharide-diphtheria toxoid conjugate vaccines. AB - Protein-polysaccharide conjugate vaccines are large, complex molecules that present challenges in terms of characterization. Free solution capillary electrophoresis using alkaline (pH 9-10) borate or glycine/NaOH buffers permitted electrophoresis of diphtheria toxoid (Dt) or meningococcal polysaccharide-Dt conjugates as well-formed, relatively broad peaks. Resolution was observed between the conjugate and the Dt peaks for some serotypes; however, overlap between Dt and one or more conjugate peaks was observed with both buffers. Inclusion of SDS in the separation buffer at a level above the critical micelle concentration allowed separation of Dt and Dt-conjugates of meningococcal serotypes A, C, Y and W135. Using borate/SDS, a linear relationship between peak area and Dt concentration was observed between approximately 2 mg/ml and 20 microg/ml. A linear relationship between Dt peak area and injection times from 10 to 50 seconds was also observed. Capillary electrophoresis may therefore be a useful method for quantifying free protein level in meningococcal-Dt conjugate vaccines. PMID- 11214246 TI - Quantification of free polysaccharide in meningococcal polysaccharide-diphtheria toxoid conjugate vaccines. AB - A precipitation method using deoxycholate/HCI has been applied successfully to separate unconjugated free polysaccharide from carrier protein-bound material in meningococcal polysaccharide-diphtheria toxoid conjugate vaccines. The method effectively separated free and bound polysaccharide in conjugate vaccines prepared from Neisseria meningitidis serotypes A, C, W135 and Y. Free polysaccharide remained in the supernatant after deoxycholate treatment while protein-bound polysaccharide was fully precipitated. Testing by both colorimetric assay and high performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) has confirmed the selective loss of protein-bound polysaccharide in samples of conjugate vaccine or conjugate vaccine mixed with known amounts of free polysaccharide. This rapid separation method requires minimum sample handling and is specific, reproducible, and allows assessment of free polysaccharide levels in vaccines at final container concentration. PMID- 11214247 TI - Preliminary physical and chemical characterisation of Salmonella typhi VI polysaccharide. PMID- 11214248 TI - Physical and chemical parameters for the characterisation of the group C polysaccharide of the Cuban meningococcal BC vaccine. PMID- 11214249 TI - Determination of C-polysaccharide in pneumococcal polysaccharides using 1H and 31P NMR. PMID- 11214250 TI - Quantification of C-polysaccharide in Streptococcus pneumoniae polysaccharides by high-performance anion-exchange chromatography with pulsed amperometric detection. AB - A sensitive method, using high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD) has been developed for measurement of the C-polysaccharide contamination in Streptococcus pneumoniae capsular polysaccharides, which are part of the polysaccharides based vaccines for the prevention of pneumococcal infections. This method, based on the quantification by HPAEC-PAD of the ribitol released by aqueous hydrofluoric acid (HF) followed by trifluoro acid hydrolysis (TFA) of the pneumococcal polysaccharides is simple and provides both a qualitative and quantitative method for control of the polysaccharides. PMID- 11214251 TI - Physico-chemical characterization of polysaccharide vaccines. AB - An increasing number of sophisticated analytical techniques, including NMR spectroscopy, are currently being applied to the quality control of polysaccharide and polysaccharide-based vaccines. These methodologies are providing more precise and more detailed profiles of these vaccines. NMR spectroscopy also provides a convenient and powerful technique to monitor alterations of the polysaccharide in the production of protein conjugate vaccines. PMID- 11214252 TI - Physicochemical characterisation of the oligosaccharide component of vaccines. AB - Glycoconjugate vaccines are being developed against Haemophilus influenzae (Hib) and meningococcal Type A and C micro-organisms; they consist of oligosaccharides of intermediate chain length conjugated to the carrier protein CRM (a non-toxic diphtheria toxin mutant). The oligosaccharides can be quantified using specific composition analyses and their structure and identity (and pattern of acetylation) evaluated by use of NMR spectroscopy. The average molecular-size (degree of polymerisation) can be determined using colorimetric assays, qualified by analysis of authentic standards. The molecular-size distribution of these anionic oligosaccharides can be achieved using ion exchange chromatography or application of the rapid and sensitive analytical HPAEC-PAD system (high performance anion-exchange chromatography with pulsed amperometric detection). Preparative ion exchange chromatography permits the isolation of purified oligomers, which can be well-characterised using the methods described above. Molecular size can be confirmed by use of mass spectrometry. These vaccines are semi-synthetic products and therefore their preparation involves several steps of chemical reaction, the detailed physicochemical characterisation of the oligosaccharide-components permits the consistent production of these well defined glycoconjugate vaccines. PMID- 11214253 TI - Monitoring of diphtheria, pertussis and tetanus toxoids by circular dichroism, fluorescence spectroscopy and size-exclusion chromatography. AB - A combination of spectroscopic and chromatographic methods has been used to monitor the quality and integrity of diphtheria, pertussis and tetanus toxoids (DTxd, PTxd and TTxd) which have been prepared from the toxins by formaldehyde treatment. Different processes for detoxifying all three toxins have yielded toxoids varying in their molecular size, including oligomers (associated monomers) and aggregates (high molecular weight complexes of non-specifically associated monomers). Changes in the intrinsic fluorescence spectra of the polypeptides have been observed in some sized fractions of DTxd and PTxd. Some physico-chemical changes have been observed to correlate with a loss of antigenicity. Spectroscopic and chromatographic methods are useful not only in monitoring the stability and consistency of vaccine starting materials, but can also be used to dissect heterogeneous toxoid preparations. PMID- 11214254 TI - Characterization of post-translationally modified recombinant protein using liquid chromatography/mass spectrometry. AB - Post-translational modification plays an important role in the biological functions of many proteins. Characterization of such modifications is crucial in the development of recombinant protein-based vaccines. Liquid Chromatography coupled with Mass Spectrometry (LC/MS) provides a powerful tool with high resolution and accuracy to characterize proteins and their post-translational modifications. The technique was applied to characterization of a Lyme vaccine protein rOspA (recombinant Outer surface protein A). The results demonstrate that LC/MS could be used to resolve and characterize various forms of post translational lipidation of the protein. It was this detailed structural information that made it possible to validate a method for quantitative determination of the lipidation forms of rOspA. PMID- 11214255 TI - Binding measurements as surrogate biological assays: surface plasmon resonance biosensors for characterizing vaccine components. AB - There is considerable interest in the possibility of using surrogate physico chemical assays for the quality control of vaccine components. Since biological activity always depends on a first binding step, the primary criterion for assessing biological activity is the ability of a vaccine component to bind specifically in a binding assay. Biosensor instruments that measure binding kinetics with considerable ease and precision are used increasingly to assess the quality of antigens intended for vaccination as well as the binding affinity of antibodies elicited by vaccination. The most widely used biosensor instrument is the BIACORE and its mode of operation is briefly described. The use of biosensors for measuring the active concentration of biomolecules and for assessing the probable effectiveness of vaccine-induced antibodies is described. PMID- 11214256 TI - Selection of putative immunogenic peptides by molecular modelling of the urease of Helicobacter pylori. AB - Computational methods such as molecular modelling are becoming an increasingly useful means of rationalising experimental data and creating a hypothesis that can suggest new experiments. In this report we discuss the application of molecular modelling methods to aid the selection of feasible peptide epitopes of the urease enzyme from Helicobacter pylori, an important vaccine candidate. Surface exposure was chosen as a criterion for the selection of three peptides which each had different levels of accessibility according to the 3D model. Antibodies raised against these peptides were analysed for their immunoreactivity with the holo enzyme. Only one anti-peptide antibody showed good reactivity with the urease. Our findings emphasise that surface exposure of peptide is not the only important criterion for the selection of immunogenic peptides. PMID- 11214257 TI - Mining genomes and mapping proteomes: identification and characterization of protein subunit vaccines. AB - Currently, there is an extensive and unprecedented effort to obtain the complete nucleotide sequence of the complex genomes of many micro-organisms. In this post genomic era, based on the availability of the entire genome sequence of an organism, three new disciplines of molecular biology have emerged: genomics, transcriptional profiling and proteomics. All these technologies have the potential to accelerate the process of identifying protective protein antigens as subunit vaccine targets as well as validating and extending the range of available candidate antigens. The progress of these technologies has led to the origination of the science of bioinformatics for management and critical evaluation of the large amount of information generated. Although genomics, transcriptional profiling and proteomics are each based on different principles, there is considerable synergy between them. Appropriate application of any one, or a combination of two or more of these approaches, coupled with bioinformatics, would allow identification of a short-list of vaccine candidates from the entire list of several hundreds to thousands of proteins encoded by the genome. These candidates would then require usual channelling through the subsequent process involving recombinant expression, purification and testing for immunogenicity and protective efficacy. PMID- 11214259 TI - On becoming a virtual editor. PMID- 11214258 TI - Characterization of saccharide-CRM197 conjugate vaccines. AB - A seven-valent pneumococcal conjugate and a Group C Meningococcal conjugate are at the late stage of development. Clinical studies have demonstrated the efficacy and safety of these vaccines and licensure of these vaccines will be approved in the near future. Several new techniques have been proposed for characterizing polysaccharide-protein conjugates and their production intermediates. We are evaluating some of these new techniques, particularly NMR and MALLS, to determine whether or not they provide useful information for conjugate production. In the production of polysaccharide protein conjugates, the degree of saccharide activation, location of activation site, and the molecular weight of activated saccharides may typically be determined. In our evaluation, techniques such as NMR and MALLS may have a limited applicability for testing polysaccharides and activated saccharides. PMID- 11214260 TI - Continuous cardiac output monitoring system. AB - A continuous cardiac output monitoring system has been developed in the laboratory to allow the real-time measurement of the cardiac output. This form of continuous cardiac output measurement allows the doctor to view the beat-to-beat cardiac output and can be employed to measure artery constrictions as well. The sensor comprises a laser Doppler velocimeter and an impedance measurement unit. The laser Doppler velocimeter is capable of measuring bi-directional blood flow within the vessel while the impedance measurement unit determines the cross sectional area of the vessel. In laboratory tests, it was demonstrated on a heart lung machine that the product of the two parameters measured is proportional to the actual flow volume of up to 6 lmin(-1) with a mean percentage error of 12.4% and a mean square error of 0.09 (using the lmin(-1) scale) were obtained. This is significantly more accurate than the measurement made using the thermodilution cathether. PMID- 11214261 TI - A knowledge-based technique for automated detection of ischaemic episodes in long duration electrocardiograms. AB - A novel method for the detection of ischaemic episodes in long duration ECGs is proposed. It includes noise handling, feature extraction, rule-based beat classification, sliding window classification and ischaemic episode identification, all integrated in a four-stage procedure. It can be executed in real time and is able to provide explanations for the diagnostic decisions obtained. The method was tested on the ESC ST-T database and high scores were obtained for both sensitivity and positive predictive accuracy (93.8% and 78.5% respectively using aggregate gross statistics, and 90.7% and 80.7% using aggregate average statistics). PMID- 11214262 TI - Circadian rhythm changes in heart rate variability during chronic sound stress. AB - To study the circadian rhythm changes of the heart rate variability (HRV) during chronic sound stress, Wistar rats were implanted with telemetry transmitters and exposed to chronic ultrasound stress for 14 days. The heart rate, mean R-R intervals (mean R-R) and body temperature were monitored hourly. The spectra of five-minute heart rate variability were plotted on a log-log scale of frequency versus power spectral density, and the spectral exponent beta of the regression line of this plot was calculated. The exponent beta, heart rate (HR) and body temperature recorded hourly were plotted and fitted to sine curves to observe the circadian rhythm of these parameters. The correlation coefficient of the fitted sine curves in beta decreased from 0.644 in the control period to 0.105 in the stress period, indicating that the rhythm of beta deceased during stress. This did not occur in the other two parameters, demonstrating that the HRV exponent can assess chronic stress. PMID- 11214263 TI - Compact long-term recorder for the transabdominal foetal and maternal electrocardiogram. AB - Foetal heart rate (FHR) monitoring is a proven means of assessing foetal health during the antenatal period. Currently, the only widely available instrumentation for producing these data is based on Doppler ultrasound, a technology that is unsuitable for long-term use. For nearly a century, it has been known that the foetal electrocardiogram (FECG) can be detected using electrodes placed on the maternal abdomen. Although these signals suggest an alternative means of FHR derivation, their use has been limited owing to problems of poor signal-to-noise ratio. However, the eminent suitability of the transabdominal FECG for long-term FHR monitoring has suggested that perseverance with the technique would be worthwhile. The paper describes the design, construction and use of a compact, long-term recorder of three channels of 24 h antenatal transabdominal data. Preliminary use of the recorder in around 400 short recording sessions demonstrates that FHR records of equivalent quality to those from Doppler ultrasound-based instruments can be extracted from such data. The success of FHR derivation is, on average, around 65% of the recording period from around 20 weeks gestation (although this figure is reduced from around 28-32 weeks, and the success rates exhibit a wide range when individual subjects are considered). These results demonstrate that the technique offers, not only a means of acquiring long-term FHR data that are problematic to obtain by other means, but also a more patient-friendly alternative to the Doppler ultrasound technique. PMID- 11214264 TI - Temperature and perfusion responses of muscle and lung tissue during chronic heating in vivo. AB - For the first time, both temperature and perfusion responses have been obtained from in vivo studies of chronically heated lung and muscle tissue of calves. In each tissue, the spatial temperature distribution was measured by thermistors placed in needles at several distances from an implanted heated disc. A perfusion parameter was defined for a bioheat transfer model that describes temperature dynamics with distance from the heated disc. Estimates of perfusion were obtained by a least-squares fit of the model output to a step change in heat flux. Except for short transient experiments several times a week, a constant heat flux of 0.04, 0.06 or 0.08 Wcm(-2) was maintained at the disc surface for up to seven weeks. At the higher heat fluxes, the steady-state tissue temperature decreased with heating duration. Also, the characteristic time constants of the tissues decreased with heating duration. Muscle perfusion showed a statistically significant increase during chronic heating. Tissue adapts to chronic heating above 42 degrees C by allowing more capillary blood flow that increases heat loss to reduce tissue temperature. PMID- 11214265 TI - Otoacoustic emissions and improved pass/fail separation using wavelet analysis and time windowing. AB - A new method is presented for the purpose of improving pass/fail separation during transient evoked otoacoustic emission (TEOAE) hearing screening. The method combines signal decomposition in scales using the discrete wavelet transform, non-linear denoising and scale-dependent time windowing. The cross correlation coefficient between two subaveraged, processed TEOAE signals is used as a pass/fail criterion and assessed in relation to the pure-tone, mean hearing level. The performance is presented in terms of receiver operating characteristics for a database of 5,214 individuals. The results show that the specificity improves from 68% to 83% at a sensitivity of 90% when compared with the conventional wave reproducibility parameter. PMID- 11214266 TI - Microprocessor-based gait analysis system to retrain Trendelenburg gait. AB - A microprocessor-based gait analysis system is described that uses two electromyogram (EMG) amplifiers, two foot switches and an audio feedback device to allow the retraining of one type of improper gait, where the hip abductors (gluteus medius muscles) are weak on one side of the body, causing the opposite hip to drop during the swing phase of gait (Trendelenburg gait). As the abnormality is strictly on one side of the body in most people, the circuitry is minimised, as gait can be analysed by only comparing muscle activity in the affected gluteus medius muscle with that in the unaffected gluteus medius muscle, through the EMG. Two foot contact switches are used to help assess timing of the step cycle. If gait is different on the two sides of the body, an audio cue directs the patient to correct the abnormality by increasing activity on the affected side. The device is tested on five patients. Trendelenburg gait is reduced by an average of 29 degrees through the use of the device. The average stride length at the beginning of the study is 0.32 +/- 0.3 m. By the end of the study, the stride length is increased to 0.45 +/- 0.2 m for the entire group of five subjects. The speed of gait has increased from 1.6 +/- 0.4 kmh(-1) to 3.1 +/ 0.5km h(-1). PMID- 11214267 TI - Electric current generated by ultrasonically induced Lorentz force in biological media. AB - The ions of solutions exposed to the propagation of ultrasound in the presence of a magnetic field experience Lorentz force. Their movement gives rise to a local electric current density, which is proportional to the electric conductivity of the medium. In vitro assessment of this current is performed using simple models of biological media. A constant magnetic field of 0.35 T and 500 kHz pulsed ultrasound are used. The sensing electrodes are exposed to neither the pressure wave nor the magnetic field, thus ensuring that the signal is not due to any undesirable electrode effect. The experimental results confirm that the current is proportional to the electrical conductivity of the medium. The changes in the measured current against the width of the measurement chamber show that the electrodes only collect a fraction of the current created within the medium. The magnitude of the measured current is 50nA in a saline solution of 0.5 S/m conductivity. The technique enabled the determination of the conductivity of a porcine blood sample against haematocrit. It is concluded that this type of measurement has the potential to allow the electrical conductivity of a medium to be determined using ultrasound. PMID- 11214268 TI - Image analysis of quick phase eye movements in nystagmus with high-speed video system. AB - There are several methods of measuring horizontal, vertical and torsional nystagmus for the diagnosis of vertigo. Using Frentzel glasses, electronystagmography (ENG) and video-oculography (VOG) are common methods for observing nystagmus. In this study, a high-speed video camera is used to analyse high-speed eye movements, including three components of nystagmus, in order to monitor precisely the amplitude and velocity of the quick phase of nystagmus. To confirm the accuracy of the analysis, images of optokinetic nystagmus (OKN) evoked by a stimulating device were analysed. We obtained a high linearity with regard to the relation between the horizontal nystagmus amplitude detected with the high-speed video system and ENG (R2= 0.99). On comparison of the maximum velocities detected with 30Hz and with 250 Hz at each amplitude, the velocities calculated at 30Hz were smaller than those calculated at 250 Hz. At an amplitude of 5 degrees , the 30 Hz velocity decreased by 50%, while a decrease of 35% was observed at 15 degrees. The vertical nystagmus data obtained using high-speed VOG was different in appearance to that obtained using ENG. The torsional component of nystagmus was also measured, and was recorded in the form of a large number of sampling points. PMID- 11214269 TI - A method for detecting myocardial abnormality by using a total current-vector calculated from ST-segment deviation of a magnetocardiogram signal. AB - A simple method to determine the state of ischaemia or fibrosis of myocardial cells has been developed. This method uses the ST wave of 64-channel magnetocardiogram (MCG) signals to calculate three parameters from the current arrow map of the normal component signal of the MCG. One parameter is a total current vector that is obtained through summation of all current arrows. Another is a variance current vector calculated from the differential vector of two total current vectors at different times. The third is a flatness factor between the magnitude of the total current vector and the variance current vector. The three parameters are independent of the distance between the heart and the gradiometers. We measured the MCG signals of 29 healthy subjects, twenty patients with coronary artery disease (ten with previous myocardial infarction (MI) and ten with angina pectoris (AP)), and eight patients with cardiomyopathy (four with hypertrophic cardiomyopathy (HCM), three with dilated cardiomyopathy (DCM), and one with restrictive cardiomyopathy (RCM)). With our method, none of the healthy subjects tested positive for myocardial abnormalities, while 80% of the MI patients, 50% of the AP patients, and 100% of the cardiomyopathy patients tested positive. Although further testing is needed, we feel this simple technique enables easy diagnosis of myocardial damage. PMID- 11214270 TI - A method for detecting myocardial abnormality by using a current-ratio map calculated from an exercise-induced magnetocardiogram. AB - A method for making a current-ratio map to determine the ischaemic area of angina pectoris (AP) patients has been developed. This method uses a current-arrow map calculated using a ORS wave from 64-channel magnetocardiogram (MCG) signals. The current-ratio map can be calculated from the ratio of an exercise-induced current vector to an at-rest current vector. The MCG signals of eight patients with angina pectoris (AP) (six patients with effort AP and two patients with variant AP) and four healthy volunteers were measured before and after a two-step exercise test. The current-ratio maps of the six patients with effort AP showed three distinct patterns: a left-circumflex-artery (LCX) pattern; a right-coronary artery (RCA) pattern; and a left-anterior-descending (LAD) pattern. The maximum current ratios of these three patterns differed from those of normal patterns. The patterns of two patients with variant AP were similar to normal patterns. Furthermore, a comparison of the current-ratio map before and after percutaneous transluminal-coronary-angioplasty (PTCA) treatment indicated that the cardiac ischaemia was reduced in all patients. An appropriate criterion to diagnose abnormality in a patient with an ischaemic myocardial area seems to be a maximum current ratio exceeding 0.4 to 0.5. Based on these preliminary results, it is believed that the location of an ischaemic area (the coronary artery part) can be estimated by using the ischaemic current-ratio map pattern. PMID- 11214272 TI - Modelling the sampling volume for skin blood oxygenation measurements. AB - The absolute quantified measurement of haemoglobin skin blood saturation from collected reflectance spectra of the skin is complicated by the fact that the blood content of tissues can vary both in the spatial distribution and in the amount. These measurements require an understanding of which vascular bed is primarily responsible for the detected signal. Knowing the spatial detector depth sensitivity makes it possible to find the best range of different probe geometries for the measurements of signal from the required zones and group of vessels inside the skin. To facilitate this, a Monte Carlo simulation has been developed to estimate the sampling volume offered by fibre-optic probes with a small source-detector spacing (in the current report 250 microm, 400 microm and 800 microm). The optical properties of the modelled medium are taken to be the optical properties of the Caucasian type of skin tissue in the visible range of the spectrum. It is shown that, for a small source-detector separation (800 microm and smaller), rough boundaries between layers of different refractive index can play a significant role in skin optics. Wavy layer interfaces produce a deeper and more homogeneous distribution of photons within the skin and tend to suppress the direct channelling of photons from source to detector. The model predicts that a probe spacing of 250 microm samples primarily epidermal layers and papillary dermis, whereas spacings of 400-800 microm sample upper blood net dermis and dermis. PMID- 11214271 TI - Volume conductor effects on the spatial resolution of magnetic fields and electric potentials from gastrointestinal electrical activity. AB - An analysis of the relative capabilities of methods for magnetic and electric detection of gastrointestinal electrical activity is presented. The model employed is the first volume conductor model for magnetic fields from GEA to appear in the literature. A mathematical model is introduced for the electric potential and magnetic field from intestinal electrical activity in terms of the spatial filters that relate the bioelectric sources with the external magnetic fields and potentials. The forward spatial filters are low-pass functions of spatial frequency, so more superficial external fields and potentials contain less spatial information than fields and potentials near the source. Inverse spatial filters, which are reciprocals of the forward filters, are high-pass functions and must be regularised by windowing. Because of the conductivity discontinuities introduced by low-conductivity fat layers in the abdomen, the electric potentials recorded outside these layers required more regularisation than the magnetic fields, and thus, the spatial resolution of the magnetic fields from intestinal electrical activity is higher than the spatial resolution of the external potentials. In this study, two smooth muscle sources separated by 5cm were adequately resolved magnetically, but not resolved electrically. Thus, sources are more accurately localized and imaged using magnetic measurements than using measurements of electric potential. PMID- 11214273 TI - Evaluation of the ability to make non-invasive estimation of muscle contractile properties on the basis of the muscle belly response. AB - The histochemical and biomechanical relationships of limb muscles are examined in two groups of 15 men aged between 17 and 40 years. Seven muscles are chosen: biceps brachii, triceps brachii (TB), flexor digitorum superficialis, extensor digitorum, biceps femoris, tibialis anterior and gastrocnemius caput mediale (GCM). The aim of the preliminary study is to evaluate an alternative method based on a tensiomyographic (TMG) non-invasive measurement technique. The percentage of type I muscle fibres obtained with the histochemical method is 2.2 times higher for the slowest measured muscle (GCM) than for the fastest (TB). The contraction time of a muscle belly twitch response measured by TMG is 1.9 times higher for GCM than for TB. Statistical analysis of the data obtained by tensiomyographic and histochemical techniques shows a significant correlation between the contraction time of muscle response measured by TMG and the percentage of type I muscle fibres (correlation coefficient equals 0.93). Results of the study suggest using the TMG measuring technique as a basis for the estimation of the percentage of type I muscle fibres. PMID- 11214274 TI - Systematic methodology for the design of a flexible keel for energy-storing prosthetic feet. AB - An effective design method is suggested for a flexible keel design for energy storing prosthetic feet (ESPF). The basic, two-dimensional shape of the keel is based on anthropometric data and normal gait analysis available in the literature. Cost function is defined for the performance evaluation of the keel. Five factors and five levels of their effect on the performance of the keel are established. By use of an orthogonal array table, 25 trials of dynamic simulations of prosthetic walking are designed, from among 3,125 possible combinations, dramatically reducing the number of total simulations needed to examine sufficiently the contribution of each factor to cost function. A prosthetic walking model is built, and a dynamic simulation of prosthetic walking is performed using the finite element method. The contribution of each factor to cost function is investigated by an analysis of variance (ANOVA), and the average main effects of factors for cost function are calculated. The optimum combination of factor levels is obtained by minimisation of cost function. To examine the structural safety of the keel, the deformation and stress distribution of the keel are investigated by static analysis, and failure indices are calculated by three failure criteria. Finally, the optimum flexible keel is designed with increased energy storage capacity, without failure, and suitable for more active prosthetic walking; the recoverable strain energy stored in the optimum ESPF keel is 25.8J. PMID- 11214275 TI - Automatic recognition of vertebral landmarks in fluoroscopic sequences for analysis of intervertebral kinematics. AB - Intervertebral kinematics closely relates to the functionality of the spinal segments. Direct measurement of the intervertebral kinematics in vivo is very problematic. The use of a fluoroscopic device can provide continuous screening of the lumbar tract during patient spontaneous motion, with an acceptable, low X-ray dose. The kinematic analysis is intended to be limited to planar motion. Kinematic parameters are computed from vertebral landmarks on each frame of the image sequence. Landmarks are normally selected manually in spite of the fact that this is subjective, tedious to perform and regarded as one of the major contributors to errors in the computed kinematic parameters. The aim of this work is to present an innovative method for the automatic recognition of vertebral landmarks throughout a fluoroscopic image sequence to provide an objective and more precise quantification of intervertebral kinematics. The recognition procedure is based upon comparing vertebral features in two adjacent frames by means of a cross-correlation index, which is also robust despite the low signal to-noise ratio of the lumbar fluoroscopic images. To provide a quantitative assessment of this method a calibration model was used which consisted of two lumbar vertebrae linked by a universal joint. The reliability and accuracy of the kinematic measurements have been investigated. The errors are of the order of a millimetre for the localisation of the intervertebral centre of rotation and tenths of a degree for the intervertebral angle. Error analysis suggests that this method improves the accuracy of the intervertebral kinematic calculations and has the potential to automate the selection of anatomical landmarks. PMID- 11214276 TI - A fast method for calibrating video-based motion analysers using only a rigid bar. AB - Video-camera systems are widely used in biomechanics and clinical fields to measure the 3D kinematic measurements of human motion. To be used, they need to be calibrated, that is the parameters which geometrically define the cameras have to be determined. It is shown here how this can be achieved by surveying a rigid bar in motion inside the working volume, and in a very short time: less than 15 s on a Pentium III. The exterior parameters are estimated through the coplanarity constraint, the camera focal lengths through the properties of epipolar geometry and the principal points with a fast evolutionary optimisation which guarantees convergence when the initial principal points cannot be adequately estimated. The method has been widely tested on simulated and real data. Results show that its accuracy is comparable with that obtained using methods based on points of known 3D coordinates (DLT): 0.37 mm RMS error over a volume with a diagonal approximately 1.5 m. A preferential absolute reference system is obtained from the same bar motion data and is used to guide an intelligent decimation of the data. Finally, the role that the principal points play in achieving a high accuracy, which is questioned in the computer vision domain, is assessed through simulations. PMID- 11214277 TI - Automatic segmentation algorithm for the extraction of lumen region and boundary from endoscopic images. AB - A new segmentation algorithm for lumen region detection and boundary extraction from gastro-intestinal (GI) images is presented. The proposed algorithm consists of two steps. First, a preliminary region of interest (ROI) representing the GI lumen is segmented by an adaptive progressive thresholding (APT) technique. Then, an adaptive filter, the Iris filter, is applied to the ROI to determine the actual region. It has been observed that the combined APT-Iris filter technique can enhance and detect the unclear boundaries in the lumen region of GI images and thus produces a more accurate lumen region, compared with the existing techniques. Experiments are carried out to determine the maximum error on the extracted boundary with respect to an expert-annotated boundary technique. Investigations show that, based on the experimental results obtained from 50 endoscopic images, the maximum error is reduced by up to 72 pixels for a 256 x 256 image representation compared with other existing techniques. In addition, a new boundary extraction algorithm, based on a heuristic search on the neighbourhood pixels, is employed to obtain a connected single pixel width outer boundary using two preferential sequence windows. Experimental results are also presented to justify the effectiveness of the proposed algorithm. PMID- 11214278 TI - A new approach to mechanical simulation of lung behaviour: pressure-controlled and time-related piston movement. AB - A mechanical lung simulator is described (an extension of a previous mechanical simulator) which simulates normal breathing and artificial ventilation in patients. The extended integration of hardware and software offers many new possibilities and advantages over the former simulator. The properties of components which simulate elastance and airway resistance of the lung are defined in software rather than by the mechanical properties of the components alone. Therefore, a more flexible simulation of non-linear behaviour and the cross-over effects of lung properties is obtained. Furthermore, the range of lung compliance is extended to simulate patients with emphysema. The dependency of airway resistance on lung recoil pressure and transmural pressure of the airways can also be simulated. The new approach enables one to incorporate time-related mechanics such as the influence of lung viscosity or cardiac oscillation. The different relations defined in the software can be changed from breath to breath. Three simulations are presented: (1) computer-controlled expiration in the artificially ventilated lung; (2) simulation of normal breathing; and (3) simulation of viscoelastance and cardiac influences during artificial ventilation. The mechanical simulator provides a reproducible and flexible environment for testing new software and equipment in the lung function laboratory and in intensive care, and can be used for instruction and training. PMID- 11214280 TI - Greece should abandon a short-sighted policy. PMID- 11214281 TI - Post-genomic cultures. PMID- 11214282 TI - Ethics watchdog to oversee drugs trials in Third World. PMID- 11214279 TI - Neural morphological effects of long-term implantation of the self-sizing spiral cuff nerve electrode. AB - The paper reports on the histological effects of chronic implantation of self sizing spiral cuff nerve electrodes on the cat sciatic nerve. The implantation period is about 4.4 months. Four different experimental conditions are evaluated: control, sham, bare cuff (cuffs without contacts and leads) and full cuff. The total number of axons in the nerves of the control group is compared with the three other groups. The surface occupied by collagen fibres in the nerve section, perineurium thickness, fibre diameter and myelin thickness are also measured. The average number of axons in the control nerves is found to be 16,416 (+/- 1,509) and does not differ significantly from the three other groups (p > 0.1). Collagen measurements show an extrafascicular epineurial fibrosis in the two implanted groups that is found to be significantly different (p < 0.05). No differences are encountered in the perineurium thickness analysis. Fibre diameter distributions show a regular bimodal pattern for all groups. Centrality (mean and Pm) and dispersion statistics (P25 and P75) extracted from fibre diameter distributions do not reveal significant differences. Myelin thickness distributions are also similar for all groups, as well as centrality and dispersion statistics. The present morphometrical results suggest that the effects produced by a chronic spiral cuff implant on this animal model are negligible. PMID- 11214284 TI - Weapons labs escape FBI action. PMID- 11214283 TI - Hughes Institute will put down roots to develop research tools. PMID- 11214285 TI - Journal will publish accused scientist's work. PMID- 11214286 TI - Canada pours funds into health research. PMID- 11214287 TI - BSE crisis sinks German public biotech programme. PMID- 11214288 TI - Poor coordination 'wastes US research into global change'. PMID- 11214289 TI - Bank raids malaria centre in dispute over landlord's debt. PMID- 11214290 TI - Designer rice to combat diet deficiencies makes its debut. PMID- 11214291 TI - Commercial sector scores success with whole rice genome. PMID- 11214292 TI - Bill Gates provides funding boost to AIDS vaccine. PMID- 11214294 TI - Informatics. Digital history. PMID- 11214293 TI - Hazard management. Taming Africa's killer lake. PMID- 11214295 TI - Changing patent laws could be a healthy move to combat resistance. PMID- 11214296 TI - We need both computer models and experiments. PMID- 11214298 TI - Back to the future from 1888. PMID- 11214297 TI - Why Pauling didn't solve the structure of DNA. PMID- 11214299 TI - A never-ending story. PMID- 11214301 TI - Fluid dynamics. That sinking feeling. PMID- 11214300 TI - Fusion needs more than SNAREs. PMID- 11214303 TI - A laser that turns down the heat. PMID- 11214302 TI - Functional genomics. Silent genes given voice. PMID- 11214304 TI - Structural biology. Pumping DNA. PMID- 11214305 TI - Ultrafast colour displays. PMID- 11214306 TI - Oceanography. The Rossby rototiller. PMID- 11214307 TI - Vascular biology. Targeted delivery of nitric oxide. PMID- 11214308 TI - A fern that hyperaccumulates arsenic. PMID- 11214309 TI - Neuroperception. Superior auditory spatial tuning in conductors. PMID- 11214310 TI - Trans-complex formation by proteolipid channels in the terminal phase of membrane fusion. AB - SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) and Rab-GTPases, together with their cofactors, mediate the attachment step in the membrane fusion of vesicles. But how bilayer mixing--the subsequent core process of fusion--is catalysed remains unclear. Ca2+/calmodulin controls this terminal process in many intracellular fusion events. Here we identify V0, the membrane-integral sector of the vacuolar H+-ATPase, as a target of calmodulin on yeast vacuoles. Between docking and bilayer fusion, V0 sectors from opposing membranes form complexes. V0 trans-complex formation occurs downstream from trans SNARE pairing, and depends on both the Rab-GTPase Ypt7 and calmodulin. The maintenance of existing complexes and completion of fusion are independent of trans-SNARE pairs. Reconstituted proteolipids form sealed channels, which can expand to form aqueous pores in a Ca2+/calmodulin-dependent fashion. V0 trans complexes may therefore form a continuous, proteolipid-lined channel at the fusion site. We propose that radial expansion of such a protein pore may be a mechanism for intracellular membrane fusion. PMID- 11214311 TI - Rapid collisional evolution of comets during the formation of the Oort cloud. AB - The Oort cloud of comets was formed by the ejection of icy planetesimals from the region of giant planets--Jupiter, Saturn, Uranus and Neptune--during their formation. Dynamical simulations have previously shown that comets reach the Oort cloud only after being perturbed into eccentric orbits that result in close encounters with the giant planets, which then eject them to distant orbits about 10(4) to 10(5) AU from the Sun (1 AU is the average Earth-Sun distance). All of the Oort cloud models constructed until now simulate its formation using only gravitational effects; these include the influence of the Sun, the planets and external perturbers such as passing stars and Galactic tides. Here we show that physical collisions between comets and small debris play a fundamental and hitherto unexplored role throughout most of the ejection process. For standard models of the protosolar nebula (starting with a minimum-mass nebula) we find that collisional evolution of comets is so severe that their erosional lifetimes are much shorter than the timescale for dynamical ejection. It therefore appears that collisions will prevent most comets escaping from most locations in the region of the giant planets until the disk mass there declines sufficiently that the dynamical ejection timescale is shorter than the collisional lifetime. One consequence is that the total mass of comets in the Oort cloud may be less than currently believed. PMID- 11214312 TI - Two coexisting vortex phases in the peak effect regime in a superconductor. AB - The critical current in the vortex phase of a type-II superconductor such as NbSe2 displays a striking anomaly in the vicinity of the superconductor-to-normal metal transition. Instead of going to zero smoothly, it rebounds to a sharp and pronounced maximum, just before vanishing at the transition. This counter intuitive phenomenon, known as the peak effect, has remained an unsolved problem for 40 years. Here we use a scanning a.c. Hall microscope to visualize the real space distribution of the critical current in NbSe2. We show that in the peak effect regime two distinct vortex-matter phases with intrinsically different pinning strengths coexist on a macroscopic scale. The composition of the two phase mixture and the transformation of one phase into another are responsible for the history effects and anomalous voltage response commonly seen when external parameters such as temperature, magnetic field or transport current are varied. We argue that the observed phase coexistence is, in fact, the hallmark of a disorder-driven non-thermal phase transition. PMID- 11214313 TI - An effective gravitational temperature for sedimentation. AB - The slow sedimentation of suspensions of solid particles in a fluid results in complex phenomena that are poorly understood. For a low volume fraction (phi) of particles, long-range hydrodynamic interactions result in surprising spatial correlations in the velocity fluctuations; these are reminiscent of turbulence, even though the Reynolds number is very low. At higher values of phi, the behaviour of sedimentation remains unclear; the upward back-flow of fluid becomes increasingly important, while collisions and crowding further complicate inter particle interactions. Concepts from equilibrium statistical mechanics could in principle be used to describe the fluctuations and thereby provide a unified picture of sedimentation, but one essential ingredient--an effective temperature that provides a mechanism for thermalization--is missing. Here we show that the gravitational energy of fluctuations in particle number can act as an effective temperature. Moreover, we demonstrate that the high-phi behaviour is in fact identical to that at low phi, provided that the suspension viscosity and sedimentation velocity are scaled appropriately, and that the effects of particle packing are included. PMID- 11214314 TI - Pumping of nutrients to ocean surface waters by the action of propagating planetary waves. AB - Primary productivity in the oceans is limited by the lack of nutrients in surface waters. These nutrients are mostly supplied from nutrient-rich subsurface waters through upwelling and vertical mixing, but in the ocean gyres these mechanisms do not fully account for the observed productivity. Recently, the upward pumping of nutrients, through the action of eddies, has been shown to account for the remainder of the primary productivity; however, these were regional studies which focused on mesoscale (100-km-scale) eddies. Here we analyse remotely sensed chlorophyll and sea-surface-height data collected over two years and show that 1,000-km-scale planetary waves, which propagate in a westward direction in the oceans, are associated with about 5 to 20% of the observed variability in chlorophyll concentration (after low-frequency and large-scale variations are removed from the data). Enhanced primary production is the likely explanation for this observation, and if that is the case, propagating disturbances introduce nutrients to surface waters on a global scale--similar to the nutrient pumping that occurs within distinct eddies. PMID- 11214315 TI - Aerogeophysical measurements of collapse-prone hydrothermally altered zones at Mount Rainier volcano. AB - Hydrothermally altered rocks can weaken volcanoes, increasing the potential for catastrophic sector collapses that can lead to destructive debris flows. Evaluating the hazards associated with such alteration is difficult because alteration has been mapped on few active volcanoes and the distribution and severity of subsurface alteration is largely unknown on any active volcano. At Mount Rainier volcano (Washington, USA), collapses of hydrothermally altered edifice flanks have generated numerous extensive debris flows and future collapses could threaten areas that are now densely populated. Preliminary geological mapping and remote-sensing data indicated that exposed alteration is contained in a dyke-controlled belt trending east-west that passes through the volcano's summit. But here we present helicopter-borne electromagnetic and magnetic data, combined with detailed geological mapping, to show that appreciable thicknesses of mostly buried hydrothermally altered rock lie mainly in the upper west flank of Mount Rainier. We identify this as the likely source for future large debris flows. But as negligible amounts of highly altered rock lie in the volcano's core, this might impede collapse retrogression and so limit the volumes and inundation areas of future debris flows. Our results demonstrate that high-resolution geophysical and geological observations can yield unprecedented views of the three-dimensional distribution of altered rock. PMID- 11214316 TI - Unexpected diversity of small eukaryotes in deep-sea Antarctic plankton. AB - Phylogenetic information from ribosomal RNA genes directly amplified from the environment changed our view of the biosphere, revealing an extraordinary diversity of previously undetected prokaryotic lineages. Using ribosomal RNA genes from marine picoplankton, several new groups of bacteria and archaea have been identified, some of which are abundant. Little is known, however, about the diversity of the smallest planktonic eukaryotes, and available information in general concerns the phytoplankton of the euphotic region. Here we recover eukaryotes in the size fraction 0.2-5 microm from the aphotic zone (250-3,000 m deep) in the Antarctic polar front. The most diverse and relatively abundant were two new groups of alveolate sequences, related to dinoflagellates that are found at all studied depths. These may be important components of the microbial community in the deep ocean. Their phylogenetic position suggests a radiation early in the evolution of alveolates. PMID- 11214317 TI - Oceanic 18S rDNA sequences from picoplankton reveal unsuspected eukaryotic diversity. AB - Picoplankton--cells with a diameter of less than 3 microm--are the dominant contributors to both primary production and biomass in open oceanic regions. However, compared with the prokaryotes, the eukaryotic component of picoplankton is still poorly known. Recent discoveries of new eukaryotic algal taxa based on picoplankton cultures suggest the existence of many undiscovered taxa. Conventional approaches based on phenotypic criteria have limitations in depicting picoplankton composition due to their tiny size and lack of distinctive taxonomic characters. Here we analyse, using an approach that has been very successful for prokaryotes but has so far seldom been applied to eukaryotes, 35 full sequences of the small-subunit (18S) ribosomal RNA gene derived from a picoplanktonic assemblage collected at a depth of 75 m in the equatorial Pacific Ocean, and show that there is a high diversity of picoeukaryotes. Most of the sequences were previously unknown but could still be assigned to important marine phyla including prasinophytes, haptophytes, dinoflagellates, stramenopiles, choanoflagellates and acantharians. We also found a novel lineage, closely related to dinoflagellates and not previously described. PMID- 11214318 TI - Parallel adaptive radiations in two major clades of placental mammals. AB - Higher level relationships among placental mammals, as well as the historical biogeography and morphological diversification of this group, remain unclear. Here we analyse independent molecular data sets, having aligned lengths of DNA of 5,708 and 2,947 base pairs, respectively, for all orders of placental mammals. Phylogenetic analyses resolve placental orders into four groups: Xenarthra, Afrotheria, Laurasiatheria, and Euarchonta plus Glires. The first three groups are consistently monophyletic with different methods of analysis. Euarchonta plus Glires is monophyletic or paraphyletic depending on the phylogenetic method. A unique nine-base-pair deletion in exon 11 of the BRCA1 gene provides additional support for the monophyly of Afrotheria, which includes proboscideans, sirenians, hyracoids, tubulidentates, macroscelideans, chrysochlorids and tenrecids. Laurasiatheria contains cetartiodactyls, perissodactyls, carnivores, pangolins, bats and eulipotyphlan insectivores. Parallel adaptive radiations have occurred within Laurasiatheria and Afrotheria. In each group, there are aquatic, ungulate and insectivore-like forms. PMID- 11214319 TI - Molecular phylogenetics and the origins of placental mammals. AB - The precise hierarchy of ancient divergence events that led to the present assemblage of modern placental mammals has been an area of controversy among morphologists, palaeontologists and molecular evolutionists. Here we address the potential weaknesses of limited character and taxon sampling in a comprehensive molecular phylogenetic analysis of 64 species sampled across all extant orders of placental mammals. We examined sequence variation in 18 homologous gene segments (including nearly 10,000 base pairs) that were selected for maximal phylogenetic informativeness in resolving the hierarchy of early mammalian divergence. Phylogenetic analyses identify four primary superordinal clades: (I) Afrotheria (elephants, manatees, hyraxes, tenrecs, aardvark and elephant shrews); (II) Xenarthra (sloths, anteaters and armadillos); (III) Glires (rodents and lagomorphs), as a sister taxon to primates, flying lemurs and tree shrews; and (IV) the remaining orders of placental mammals (cetaceans, artiodactyls, perissodactyls, carnivores, pangolins, bats and core insectivores). Our results provide new insight into the pattern of the early placental mammal radiation. PMID- 11214320 TI - Horsetails and ferns are a monophyletic group and the closest living relatives to seed plants. AB - Most of the 470-million-year history of plants on land belongs to bryophytes, pteridophytes and gymnosperms, which eventually yielded to the ecological dominance by angiosperms 90 Myr ago. Our knowledge of angiosperm phylogeny, particularly the branching order of the earliest lineages, has recently been increased by the concurrence of multigene sequence analyses. However, reconstructing relationships for all the main lineages of vascular plants that diverged since the Devonian period has remained a challenge. Here we report phylogenetic analyses of combined data--from morphology and from four genes--for 35 representatives from all the main lineages of land plants. We show that there are three monophyletic groups of extant vascular plants: (1) lycophytes, (2) seed plants and (3) a clade including equisetophytes (horsetails), psilotophytes (whisk ferns) and all eusporangiate and leptosporangiate ferns. Our maximum likelihood analysis shows unambiguously that horsetails and ferns together are the closest relatives to seed plants. This refutes the prevailing view that horsetails and ferns are transitional evolutionary grades between bryophytes and seed plants, and has important implications for our understanding of the development and evolution of plants. PMID- 11214321 TI - Export by red blood cells of nitric oxide bioactivity. AB - Previous studies support a model in which the physiological O2 gradient is transduced by haemoglobin into the coordinate release from red blood cells of O2 and nitric oxide (NO)-derived vasoactivity to optimize oxygen delivery in the arterial periphery. But whereas both O2 and NO diffuse into red blood cells, only O2 can diffuse out. Thus, for the dilation of blood vessels by red blood cells, there must be a mechanism to export NO-related vasoactivity, and current models of NO-mediated intercellular communication should be revised. Here we show that in human erythrocytes haemoglobin-derived S-nitrosothiol (SNO), generated from imported NO, is associated predominantly with the red blood cell membrane, and principally with cysteine residues in the haemoglobin-binding cytoplasmic domain of the anion exchanger AE1. Interaction with AE1 promotes the deoxygenated structure in SNO-haemoglobin, which subserves NO group transfer to the membrane. Furthermore, we show that vasodilatory activity is released from this membrane precinct by deoxygenation. Thus, the oxygen-regulated cellular mechanism that couples the synthesis and export of haemoglobin-derived NO bioactivity operates, at least in part, through formation of AE1-SNO at the membrane-cytosol interface. PMID- 11214322 TI - Scabrous complexes with Notch to mediate boundary formation. AB - The mechanisms that establish and sharpen pattern across epithelia are poorly understood. In the developing nervous system, the first pattern elements appear as 'proneural clusters' In the morphogenetic furrow of the immature Drosophila retina proneural clusters emerge in a wave as a patterned array of 6-10-cell groups, which are recognizable by expression of Atonal, a basic helix-loop-helix transcription factor that is required to establish and pattern the first cell fate. The establishment and subsequent patterning of Atonal expression requires activity of the signalling transmembrane receptor Notch. Here we present in vivo and biochemical evidence that the secreted protein Scabrous associates with Notch, and can stabilize Notch protein at the surface. The result is a regulation of Notch activity that sharpens proneural cluster boundaries and ensures establishment of single pioneer neurons. PMID- 11214323 TI - Polarity controls forces governing asymmetric spindle positioning in the Caenorhabditis elegans embryo. AB - Cell divisions that create daughter cells of different sizes are crucial for the generation of cell diversity during animal development. In such asymmetric divisions, the mitotic spindle must be asymmetrically positioned at the end of anaphase. The mechanisms by which cell polarity translates to asymmetric spindle positioning remain unclear. Here we examine the nature of the forces governing asymmetric spindle positioning in the single-cell-stage Caenorhabditis elegans embryo. To reveal the forces that act on each spindle pole, we removed the central spindle in living embryos either physically with an ultraviolet laser microbeam, or genetically by RNA-mediated interference of a kinesin. We show that pulling forces external to the spindle act on the two spindle poles. A stronger net force acts on the posterior pole, thereby explaining the overall posterior displacement seen in wild-type embryos. We also show that the net force acting on each spindle pole is under control of the par genes that are required for cell polarity along the anterior-posterior embryonic axis. Finally, we discuss simple mathematical models that describe the main features of spindle pole behaviour. Our work suggests a mechanism for generating asymmetry in spindle positioning by varying the net pulling force that acts on each spindle pole, thus allowing for the generation of daughter cells with different sizes. PMID- 11214324 TI - Normal human mammary epithelial cells spontaneously escape senescence and acquire genomic changes. AB - Senescence and genomic integrity are thought to be important barriers in the development of malignant lesions. Human fibroblasts undergo a limited number of cell divisions before entering an irreversible arrest, called senescence. Here we show that human mammary epithelial cells (HMECs) do not conform to this paradigm of senescence. In contrast to fibroblasts, HMECs exhibit an initial growth phase that is followed by a transient growth plateau (termed selection or M0; refs 3 5), from which proliferative cells emerge to undergo further population doublings (approximately 20-70), before entering a second growth plateau (previously termed senescence or M1; refs 4-6). We find that the first growth plateau exhibits characteristics of senescence but is not an insurmountable barrier to further growth. HMECs emerge from senescence, exhibit eroding telomeric sequences and ultimately enter telomere-based crisis to generate the types of chromosomal abnormalities seen in the earliest lesions of breast cancer. Growth past senescent barriers may be a pivotal event in the earliest steps of carcinogenesis, providing many genetic changes that predicate oncogenic evolution. The differences between epithelial cells and fibroblasts provide new insights into the mechanistic basis of neoplastic transformation. PMID- 11214325 TI - The bacterial conjugation protein TrwB resembles ring helicases and F1-ATPase. AB - The transfer of DNA across membranes and between cells is a central biological process; however, its molecular mechanism remains unknown. In prokaryotes, trans membrane passage by bacterial conjugation, is the main route for horizontal gene transfer. It is the means for rapid acquisition of new genetic information, including antibiotic resistance by pathogens. Trans-kingdom gene transfer from bacteria to plants or fungi and even bacterial sporulation are special cases of conjugation. An integral membrane DNA-binding protein, called TrwB in the Escherichia coli R388 conjugative system, is essential for the conjugation process. This large multimeric protein is responsible for recruiting the relaxosome DNA-protein complex, and participates in the transfer of a single DNA strand during cell mating. Here we report the three-dimensional structure of a soluble variant of TrwB. The molecule consists of two domains: a nucleotide binding domain of alpha/beta topology, reminiscent of RecA and DNA ring helicases, and an all-alpha domain. Six equivalent protein monomers associate to form an almost spherical quaternary structure that is strikingly similar to F1 ATPase. A central channel, 20 A in width, traverses the hexamer. PMID- 11214326 TI - Three key residues form a critical contact network in a protein folding transition state. AB - Determining how a protein folds is a central problem in structural biology. The rate of folding of many proteins is determined by the transition state, so that a knowledge of its structure is essential for understanding the protein folding reaction. Here we use mutation measurements--which determine the role of individual residues in stabilizing the transition state--as restraints in a Monte Carlo sampling procedure to determine the ensemble of structures that make up the transition state. We apply this approach to the experimental data for the 98 residue protein acylphosphatase, and obtain a transition-state ensemble with the native-state topology and an average root-mean-square deviation of 6 A from the native structure. Although about 20 residues with small positional fluctuations form the structural core of this transition state, the native-like contact network of only three of these residues is sufficient to determine the overall fold of the protein. This result reveals how a nucleation mechanism involving a small number of key residues can lead to folding of a polypeptide chain to its unique native-state structure. PMID- 11214327 TI - Molecular characterization of the Smyth chicken sublines and their parental controls by RFLP and DNA fingerprint analysis. AB - The Smyth line (SL) chicken, a model for autoimmune human vitiligo, is characterized by a spontaneous posthatch epidermal pigment loss (vitiligo). Even though the immunological and morphological changes accompanying the vitiligo process have been well studied, the genetics of this phenomenon remains elusive. The SL lines have been maintained by nonpedigreed matings since their inception, and therefore, the inbreeding status is unknown. The present study was designed to provide an estimate of the inbreeding coefficients and the molecular genetic profiles of the SL sublines, each homozygous for a different MHC haplotype and their MHC-matched parental control (BL) sublines. The DNA fingerprint analysis revealed that there is a moderate level of inbreeding within the SL and BL parental sublines. Of the two SL sublines studied, SL101 had the highest level of inbreeding (0.948). Similarly, its parental control line (BL101) was more inbred than the parental subline of SL102 (BL102). The very high level of similarity between the SL sublines and their respective parental control lines is shown further by the similarity index (SI) estimates (SI between SL101 and BL101 was 0.949 and that between SL102 and BL102 was 0.932). Restriction fragment length polymorphism (RFLP) analysis of the endogenous viral genes (avian leukosis virus subgroup E, ALVE) showed that five ALVE-related BamH1 fragments were present in the SL101 and four in SL102 sublines, whereas the parental BL101 and BL102 sublines had five and six fragments, respectively. SL101 and SL102 shared two fragments, but the frequencies were different. Similarly, BL101 and BL102 shared two fragments. SL101 and BL101 shared three fragments, and SL102 and BL102 also shared three fragments. PMID- 11214328 TI - Acceptance of fresh chicken meat presented under three light sources. AB - The effect of using incandescent (INC), fluorescent (FL), and metal halide (MH) light sources on consumer preference of three different chicken cuts was investigated. For whole chicken and skinless thigh meat, INC was the preferred light source (P < 0.05). For the skinless breast meat, FL light was significantly preferred over MH but not over INC. Panelists indicated that they would buy thigh meat presented under INC and MH light but not under FL. Light reflectance data indicated that the reason was a lack of red light in the bulb output of FL light. PMID- 11214329 TI - Formation of cholesterol oxides in irradiated raw and cooked chicken meat during storage. AB - The objective of this study was to determine the effect of electron-beam irradiation on the oxidation of cholesterol in raw and cooked chicken meats with different packaging and storage times. Patties were prepared with skinless chicken breasts and legs. Half of the patties were used for raw meat study and the other half for cooked meat work. For cooked samples, patties were cooked in an electric oven to an internal temperature of 70 C. Raw and cooked meat patties were either aerobically or vacuum-packaged before irradiation. Irradiated patties were stored at 4 C up to 2 wk, and the amounts of cholesterol oxides in the patties were analyzed at 0, 7, and 14 d of storage. In raw chicken meat with vacuum packaging, 7beta-hydroxycholesterol and beta-epoxide were the only two cholesterol oxides present in significant amounts. In raw chicken meat with aerobic packaging, 7alpha-hydroxycholesterol and 7-keiocholesterol, which were not detected in vacuum-packaged raw chicken meat, were found. 7beta Hydroxycholesterol in raw chicken meat was increased by irradiation and storage time, regardless of packaging. The kinds of cholesterol oxides found in cooked meat were basically the same as those found in raw chicken, but the levels in cooked meats at all storage time were higher than those of the raw meats. With vacuum packaging, irradiation had no consistent effect on the amount of beta epoxide, 7alpha-hydroxycholesterol, or 7-ketocholesterol, but storage significantly influenced the amount of 7-ketocholesterol, 7beta hydroxycholesterol, and total cholesterol oxides in cooked chicken meat. With aerobic packaging, irradiation significantly increased the formation of 7alpha hydroxycholesterol, 7beta-hydroxycholesterol, and 7-ketocholesterol in cooked meat stored for 0 and 7 d. After 14 d of storage, however, irradiation had minor effects on the formation of cholesterol oxides in aerobically packaged cooked chicken. PMID- 11214330 TI - Effect of deboning time, muscle tensioning, and calcium chloride marination on texture characteristics of chicken breast meat. AB - Tenderness is the most important organoleptic characteristic of meat, and various methods have been developed to improve it. The purpose of this experiment was to evaluate the effect of different conditioning treatments of broiler carcasses on pH, cooking losses, shear values, R-values, and sensory tenderness of breast meat. All measurements were collected for breast muscle as follows: after 24 h of carcass aging (T1); after 24 h of carcass aging with muscle tensioning (T2); after 24 h of carcass aging with muscle tensioning, followed by muscle collection and marination in CaCl2 (T3); after hot-boning 15 min following slaughter (T4); after hot-boning 15 min following slaughter and marination in CaCl2 (T5). pH values in meat treated with CaCl2 were significantly lower than those in untreated meat from the aged carcass group (T3) or the hot-boning group (T5). Breasts from carcasses aged for 24 h (T1, T2, and T3) showed lower cooking loss than breasts harvested immediately after slaughter (T4 and T5). CaCl2 marination produced meats with cooking losses significantly higher than those observed for untreated meats. Regardless of muscle tensioning or marination treatments, aging of the carcass for 24 h (T1, T2, and T3) produced meats with lower shear values than those from hot-boned carcasses (T4 and T5). Hot-boned breasts treated with CaCl2 (T5) were judged less tender by panelists than breasts aged under muscle tensioning (T2 and T3). PMID- 11214331 TI - Evaluation of between-line variation for within-line selection against ascites in broilers. AB - Within-line opportunities for selection against ascites were studied in a data set comprising a 10-line comparison. The study attempted to reveal whether contrasts between lines provide reliable candidate traits for within-line selection. Mortality was chosen as the reference trait. As no pedigree information was available, a trait was required that related mortality to the nonmortality data. By principal component analysis, such a trait (ASC_INDIC = ascites indicator) was developed from pathology data. The composite trait ASC_INDIC ranked lines well for their mortality figures (r = 0.96), from which it was concluded that ASC_INDIC represents an underlying continuous ascites trait. Between lines, blood gas traits seemed to be the most promising traits. Within lines, performance traits appeared to be highly correlated to ascites. Comparison of within-line variation to between-line contrasts revealed considerable differences. The high correlation of the blood gas traits with mortality was not present within lines. However, although the magnitude was considerably reduced, the nature of the blood gas traits in their relationship to ascites was similar within and between lines. The study primarily demonstrates that contrasts between lines carry systematic but limited information for within-line coherence. Therefore, line contrasts must be interpreted with care when aiming to study genetic variation and coherence within lines. PMID- 11214332 TI - DNA microsatellites linked to quantitative trait loci affecting antibody response and survival rate in meat-type chickens. AB - Selection for immune response parameters may lead to improved general disease resistance. Because disease resistance and immune response are hard-to-measure quantitative traits with low to moderate heritability, they may respond more efficiently to marker-assisted selection (MAS) than to phenotypic selection. To detect DNA markers linked to quantitative trait loci (QTL) associated with immune response, a resource half-sib family of 160 backcross (BC1) and intercross (F2) birds was derived from a cross between two meat-type lines divergently selected for high or low antibody (Ab) response to Escherichia coli. By using 25 microsatellite DNA markers covering approximately 25% of the chicken genome, initial genotyping of 40% of the resource family was followed by complete genotyping of the entire family with four suggestive markers. Three of these markers exhibited significant association with immune response: (1) ADL0146 on Chromosome 2 associated with Ab to SRBC and Newcastle disease virus (NDV), (2) ADL0290 on linkage group 31 affecting Ab to NDV, and (3) ADL0298 on linkage group 34 associated with Ab to E. coli and survival. The family was also genotyped with five linked markers from two of the suggested regions, and interval mapping was applied. The results confirmed the significant effects, suggested the location of the QTL, and confirmed the genetic association between immune responses and disease resistance. These findings support the idea of improving poultry immunocompetence by MAS. PMID- 11214333 TI - Early age thermal conditioning and a dual feeding program for male broilers challenged by heat stress. AB - The effects of early age thermal conditioning (TC) and dual feeding on responses of male broilers to a thermal challenge at 34 d of age are reported. Three hundred chicks were randomly divided into two equal groups. One group was exposed to thermal conditioning (38 C, 42% relative humidity for 24 h) at the age of 5 d, and the other group was not exposed. From 11 to 41 d of age, temperature was diurnally cyclic: 26 C (1600 to 0900 h) and 30 C (0900 to 1600 h). From Day 19, a factorial (2 x 2, TC x diet) experiment was conducted using eight pens of six broilers per treatment. Diets were control diet and dual feeding of a high protein fraction (1600 to 0900 h) and an energy-rich fraction (0900 to 1600 h). Growth and feed efficiency were slightly enhanced (+4%) by thermal conditioning and slightly reduced (-4%) by dual feeding. Mortality during thermal challenge was reduced by both factors. [In not conditioned chicks (N), 31 fed a control grower diet (NG) and 12 on a dual feeding program (NDF) died; in thermal conditioned chicks (T), 18 fed a control grower diet (TG) and 11 on a dual feeding program (TDF) died.] Before the thermal challenge period, body temperature (Tb) was consistently reduced in T. During the thermal challenge period, Tb was reduced by thermal conditioning and dual feeding. Measured at the age of 32 d, Tb gave an estimation of the ability of the chickens to cope with heat stress 2 d later. Pectoral mass was increased in TG, whereas the liver and the gizzard were significantly heavier in TDF and NDF. These results suggest that thermal conditioning at 5 d of age induces a consistent metabolic change in broiler males. The dual feeding program might have induced transitory effects on heat production during the heat stress. PMID- 11214334 TI - Carcass traits, ovarian morphology and egg laying characteristics in early versus late maturing strains of commercial egg-type hens. AB - Three hundred commercial Single Comb While Leghorn (SCWL) pullets of two strains differing in age at first oviposition (early maturing = EARLY; later maturing = LATE) were reared and photostimulated at 18 wk. Selected birds of each strain were killed at weekly intervals from 17 to 23 wk, at sexual maturity, or at 68 wk of age for the study of carcass and reproductive organ traits. Egg production was recorded for surviving hens to 68 wk of age. The two strains differed in age at sexual maturity (EARLY, 137.5 d; LATE, 142.1 d). The EARLY strain birds appeared to allocate a greater proportion of nutrients to reproductive development (oviduct) from 19 to 22 wk of age than did the LATE group, which showed greater breast muscle development during this same period. The LATE strain hens were significantly heavier than the EARLY hens at sexual maturity, and this difference in BW persisted to the end of the laying period. Although total egg production did not differ between strains, the LATE strain hens had a longer prime egg laying sequence length (LATE, 70.2 d; EARLY, 52.6 d) as well as a longer mean sequence length (LATE, 12.8 d; EARLY, 8.7 d). Egg weight did not differ between strains. These data suggest that LATE lines of egg-type hens offer equivalent production efficiency due to improved rates of lay, albeit starting later. PMID- 11214335 TI - Effects of photostimulatory light intensity on ovarian morphology and carcass traits at sexual maturity in modern and antique egg-type pullets. AB - The effects of light intensity during sexual maturation on ovarian and carcass morphology at first oviposition [sexual maturity (SM)] were examined in two Single Comb White Leghorn (SCWL) strains. A modern commercial layer strain (COMM; Shaver Starcross 288) and an antique randombred control strain (ANT) were used to compare the effects of changes in laying stock on their response to varying light intensities from photostimulation (PS) until SM. Two hundred pullets from each strain were reared following COMM breeder guidelines. At 18 wk of age, 32 COMM and 32 ANT pullets were individually caged in individually lit cages and photostimulated with light intensities of 1, 5, 50, and 500 lx. Each bird was processed when it reached SM, and carcass and ovarian morphology were assessed. The ANT birds came into production 9.1 d later than the COMM birds, on average. The ANT pullets consumed 7.0% more feed per day than COMM pullets but gained at a slower rate (ANT = 12.9 g/d; COMM = 15.0 g/d). The ANT birds reached SM at a greater weight and with a smaller ovary than did COMM birds. Although the number of large yellow follicles (LYF) was similar between strains (mean = 6.72), both LYF weight and first egg weight were lower in ANT birds than in COMM birds. The COMM layer strain was more growth efficient and had a greater emphasis on ovary maintenance. Light intensity had no effect on the timing of SM or on BW at SM, indicating that all intensities used were effectively able to stimulate the sexual maturation process. However, ovary weight and number of LYF exhibited an increasing dose response to light intensity, particularly in the COMM birds. Overall, the birds photostimulated with 1 lx of light had reduced ovary development and were heavier than their counterparts exposed to 50 and 500 lx. Within the ANT strain, LYF numbers were not significantly affected by light intensities, whereas, within the COMM strain, LYF numbers were 4.88, 6.63, 7.88, and 8.13 for the 1-, 5-, 50-, and 500-lx intensity groups, respectively. Although light intensity did not affect the rate of sexual maturation, it altered ovarian morphology and carcass lipid stores. A light intensity of 1 lx was limiting to ovarian follicle formation and caused increased carcass weight compared with birds on higher light intensity treatments. The COMM birds were more negatively affected by low light intensity than were the ANT birds, indicating that light intensity may be a more critical environmental factor with modern, highly efficient SCWL strains than has previously been thought. Light intensity can affect the reproductive development and likely the associated egg production potential of modern layer stocks. PMID- 11214336 TI - Recovery and characterization of by-products from egg processing plant wastewater using coagulants. AB - The effectiveness of precipitation or coagulation technology to treat commercial egg processing plant wastewater, using such coagulants as lignosulfonate, bentonite, carboxymethylcellulose, and ferric chloride, was evaluated. For simulated and industrial waste-water, chemical oxygen demand, turbidity, and total solids were reduced over 90, 97, and 95%, respectively, for all coagulants tested. Protein and fat recoveries were over 95% for all coagulants. The optimal coagulant concentration for maximum by-product recovery depended on initial wastewater concentrations of protein, total solids, and fat. The dried by products contained high concentrations of protein (30 to 50%) and fat (30 to 40%) and had similar essential amino acid profiles as standard proteins from the United Nations Food and Agricultural Organization (FAO). The relative protein digestibilities of each recovered solid (carboxymethycellulose, lignosulfonate, bentonite, and ferric chloride) and corn meal relative to a liquid whole egg standard were approximately 80, 90, 60, 30, and 56%, respectively. These compositional and in vitro digestibility studies suggest that the recovered by products could be useful as livestock feed ingredients or for other applications. PMID- 11214337 TI - Screening for highly heterozygous chickens in outbred commercial broiler lines to increase detection power for mapping quantitative trait loci. AB - Two commercial broiler lines were used in an experiment to map quantitative trait loci (QTL) affecting disease resistance. Chickens from these lines were genotyped with 27 microsatellite markers to estimate heterozygosity and polymorphism information content (PIC), the probability that one parent is heterozygous at a marker locus and the other has a different genotype. Heterozygosity estimated from allelic frequencies was 0.52 for the two lines; however, heterozygosity calculated from actual counts of heterozygous loci was much lower (0.36) than the estimated heterozygosity. The PIC was 0.45 in these lines, and average allele number per marker locus was about 3.5. Twenty-five males produced from a cross between these two lines were screened with the DNA markers to select birds with high heterozygosity at marker loci. Mating simulation showed that uninformative matings could be reduced by about 5% if 12 pairs of males and females with the highest heterozygosity at marker loci were selected, which was about a 25% reduction in total uninformative matings. This experiment demonstrated that the heterozygosity and PIC in commercial broiler lines were low and selection for the birds with high heterozygosity at marker loci could increase informative content in chickens used in the experiments of QTL mapping, thus increasing detection power for QTL mapping. PMID- 11214338 TI - Farm and management variables linked to fecal shedding of Campylobacter and Salmonella in commercial squab production. AB - A cross-sectional study was performed to determine the relationship of farm variables and management practices to fecal shedding of Campylobacter or Salmonella on commercial squab (young pigeon) farms. A detailed survey provided information on biosecurity, cleaning and disinfection, bird health, vector control, and loft and pen. Twenty pigeons on each of 12 farms were cultured before and after the producers completed a voluntary quality assurance training program (QAP), based on principles of hazard analysis critical control point (HACCP). The prevalence of positive samples for Salmonella and C. jejuni was 1/480 (0.21%) and 19/480 (3.96%), respectively. Campylobacter was present on one farm during both visits; three farms during the first visit, and three farms during the second visit. Analysis by fixed-effects logistic regression showed the probability of having a positive C. jejuni culture was increased by not using dry manure in the nesting material, not cleaning shipping crates, cleaning landing boards, and by increased frequency of chemical disinfection of water. Having a positive parent and higher numbers of squab per pen (density) were also associated with higher odds of being positive for C. jejuni. Factors not associated with a positive C. jejuni culture included, other avian species on the farm, type of shipping crate, covered drinkers, fly problems, bird age, level of nest box within the loft, and QAP training. Prevalence of food safety pathogens was extremely low on the squab facilities tested as compared with reports from commercial broiler or turkey flocks. This observation suggests that one or more farm variables or management practices were effectively reducing infection, or possibly a species-related difference existed in carriage rates and shedding of pathogens. These results emphasize critical control points for food safety pathogens may vary widely, and the formulation of effective QAP programs are dependent on science-based knowledge of diverse animal production systems. PMID- 11214339 TI - Dietary fatty acid profile modifies abdominal fat deposition in broiler chickens. AB - An experiment was conducted to study the effect of different dietary fatty acid profiles on abdominal fat deposition in broilers. Diets with four types of fats (tallow, olive oil, sunflower oil, and linseed oil), at two levels of fat inclusion (either 6 or 10%), were administered to males from 21 to 42 d and to females from 21 to 49 d of age. The sexes were studied separately. Performance parameters, abdominal fat, muscle fat and cholesterol, and fatty acid profile of thigh, breast, and abdominal fat were determined. Broilers fed sunflower and linseed oils presented better values of feed efficiency. Abdominal fat and cholesterol content of thigh muscle were significantly lower in animals fed sunflower and linseed oils than in those fed tallow or olive oil (P < 0.001). In females, abdominal fat increased with level of fat inclusion only in birds fed tallow or olive oil, whereas it remained constant in birds fed sunflower or linseed oil. Muscle fat content was lower for birds fed tallow or olive oil but not significantly. The fatty acid profile of the different tissues reflected dietary fatty acid profile. Monounsaturated fatty acids were higher in abdominal fat, whereas polyunsaturated fatty acids were higher in muscle fat. These results suggest that polyunsaturated fatty acids produce lower abdominal fat deposition than saturated or monounsaturated fatty acids. PMID- 11214340 TI - Indicators of nutritional value of hydrolyzed feather meal. AB - Processing pressure and time were evaluated for their effects on feather meal protein quality. Feathers were collected from a commercial broiler plant and hydrolyzed with saturated steam in an experimental batch hydrolyzer. A constant time series (36 min) was completed to evaluate the effect of increasing pressure (207 to 517 kPa) on nutritional value. Feather meal processed at the lowest pressure had the highest nutritional value, and vice versa. True amino acid availability determined with force-fed White Leghorn cockerels demonstrated that increasing pressure decreased true available (TA) cystine (P < 0.05) more than any other amino acid. Sulfur content and acid detergent fiber were positively correlated with TA sulfur amino acid content; bulk density, 0.2% pepsin digestible protein, and acid detergent soluble protein were negatively correlated with TA sulfur amino acid content. Increased steam pressure also resulted in decreased, undegraded intake protein. Various combinations of time (106 to 4.5 min) and pressure (207 to 724 kPa) were used to prepare a constant density series (483 kg/m3). In this series, feather meals were similar in nutritional value. There was no indication that high hydrolysis pressure was detrimental to feather meal quality, if the appropriate time was used. These results suggest that sulfur content and bulk density can be used to monitor feather meal quality. PMID- 11214341 TI - Zinc bioavailability in tetrabasic zinc chloride and the dietary zinc requirement of young chicks fed a soy concentrate diet. AB - Three chick assays were conducted to determine a bioavailable Zn requirement and to establish a Zn relative bioavailability (RBV) value for tetrabasic Zn chloride [TBZC, i.e., Zn5Cl2(OH)8]. In Assay 1, 8-d-old chicks were fed a Zn-deficient soy concentrate diet (8.8 mg/kg bioavailable Zn) supplemented with 0, 5.81, 10.81, 15.10, and 20.25 mg Zn/kg from ZnSO4.7H2O for 14 d to establish a linear response range and estimate a bioavailable Zn requirement. Weight gain of chicks increased linearly (P < 0.01; r2 = 0.99) when the first three levels of Zn were fed. Broken line analysis of the weight gain data indicated a bioavailable Zn requirement of 22.4 mg/kg. In Assay 2, RBV of Zn in TBZC was determined by multiple-linear regression slope-ratio methodology. The Zn-deficient basal diet was supplemented with 0, 5.81, and 10.81 mg Zn/kg from ZnSO4.7H2O to produce a linear growth response as determined in Assay 1. The same basal diet was supplemented with 5.38 and 10.81 mg Zn/kg from TBZC. The RBV of Zn in TBZC was found to be 102%, which was not different (P > 0.10) from 100%. A third assay was conducted as described for Assay 2, and the RBV of Zn in TBZC was 111%, which was not different from 100%. In summary, the RBV of Zn in TBZC was not different from that of ZnSO4.7H2O, and the minimal bioavailable Zn requirement for chicks 1 to 3 wk of age fed a soy concentrate diet was estimated at 22.4 mg/kg. PMID- 11214342 TI - The influence of drinking water containing sodium chloride on performance and eggshell quality of a modern, colored layer strain. AB - Hubbard ISA IsaBrown pullets were purchased from a commercial supplier at 16 wk of age and kept at a constant 18 C or a constant 30 C in temperature-controlled rooms. The purpose of our experiment was to determine the effect of ambient temperature on the eggshell quality responses of laying hens receiving saline drinking water with or without simultaneous supplementation of the diet with ascorbic acid or Zn methionine. Four treatments were investigated: 1) a basal layer diet (C) and local drinking water, 2) diet C and local drinking water containing 2 g NaCl/L, 3) diet C containing 200 mg ascorbic acid/kg and local drinking water containing 2 g NaCl/L, and 4) diet C with 360 mg Zinpro 100 (Zn methionine)/kg and local drinking water containing 2 g NaCl/L. The local drinking water contained <1 mmol Cl/ L. The pullets received a continuous daily photoperiod of 16 h from fluorescent lighting, and production measures were made between 20 and 60 wk of age. Production and eggshell quality were significantly reduced at 30 C compared with 18 C but were not significantly affected by the dietary and water treatments. The results indicated that the IsaBrown hens were relatively insensitive to intakes of NaCl from the drinking water at concentrations of 2 g/L. This lack of sensitivity in eggshell quality contrasts with the majority of published reports, including earlier work with local Australian layer strains. It is suggested that this contrasting sensitivity may relate to the concentration of dietary NaCl used during the selection of layer genotypes. PMID- 11214343 TI - Temporal characteristics and incidence of photorefractoriness in turkey hens. AB - We conducted experiments to determine the incidence and temporal components of photorefractoriness (PR) in first-year turkey breeder hens after photostimulation. In turkey hens, PR may be defined as a lack of responsiveness to photoperiods that previously induced or maintained egg production and is characterized by a spontaneous cessation of lay, usually followed by molt, as well as an absence of nesting behavior. In one experiment, groups of hens were photostimulated with 18 h of light (L):6 h darkness (D) for 12, 16, 19, or 22 wk and then were exposed to 13L:11D photoperiods to induce a change in egg laying that allowed an evaluation of the photoresponsive state of each group of hens. In two other experiments individual hens were photostimulated continuously with 16L:8D for 24 or 45 wk, and the onset of PR was evaluated by the spontaneous cessation of lay. Data were collected for time to onset of PR, percentage incidence, duration of PR, and the time required for the transition from the photosensitive to the PR state. The earliest onset of PR occurred 7 wk after photostimulation, and the mean onset occurred at about 18 wk of photostimulation. Hens that expressed PR did so within an 18-wk period ending at 25 wk of photostimulation, but not all of these first-year hens expressed PR. Incidence of PR was variable at 59 and 89% in Experiments 2 and 3, respectively. The transition from a photosensitive state to an overt PR state, and therefore a laying to nonlaying state, occurred abruptly within a 2-wk period. Photorefractoriness was permanent during 45 wk of photostimulation for 11% of the PR hens. In the remaining 89% of hens, PR persisted for at least 14 wk (mean of 20.0+/-0.9) but it was not permanent, because they subsequently spontaneously recrudesced. That is, they spontaneously terminated PR. It was concluded that most, but not all, first-year turkey hens become PR and that the incidence is highly variable; PR may be relative or absolute, and absolute PR occurs abruptly but with a highly variable onset time. In most hens, PR is not permanent. PMID- 11214344 TI - HIPAA special report: final privacy rules affect all of health care. PMID- 11214345 TI - Survey shows medical errors, malpractice now leading public quality indicators. PMID- 11214346 TI - Spatial and temporal performance of the miniface (free air CO2 enrichment) system on Bog Ecosystems in northern and Central Europe. AB - The Bog Ecosystem Research Initiative (BERI) project was initiated to investigate, at five climatically different sites across Europe, the effects of elevated CO2 and N deposition on the net exchange of CO2 and CH4 between bogs and the atmosphere, and to study the effects of elevated CO2 and N deposition on the plant biodiversity of bog communities. A major challenge to investigate the effects of elevated CO2 on vegetation and ecosystems is to apply elevated CO2 concentrations to growing vegetation without changing the physical conditions like climate and radiation. Most available CO2 enrichment methods disturb the natural conditions to some degree, for instance closed chambers or open top chambers. Free Air CO2 Enrichment (FACE) systems have proven to be suitable to expose plants to elevated CO2 concentrations with minimal disturbance of their natural environment. The size and spatial scale of the vegetation studied within the BERI project allowed the use of a modified version of a small FACE system called MiniFACE. This paper describes the BERI MiniFACE design as well as its temporal and spatial performance at the five BERI field locations. The temporal performance of the MiniFACE system largely met the quality criteria defined by the FACE Protocol. One minute average CO2 concentrations measured at the centre of the ring stayed within 20% of the pre-set target for more than 95% of the time. Increased wind speeds were found to improve the MiniFACE system's temporal performance. Spatial analyses showed no apparent CO2 gradients across a ring during a 4 day period and the mean differences between each sampling point and the centre of the ring did not exceed 10%. Observations made during a windy day, causing a CO2 concentration gradient, and observations made during a calm day indicated that short term gradients tend to average out over longer periods of time. On a day with unidirectional strong winds, CO2 concentrations at the upwind side of the ring centre were higher than those made at the centre and at the downwind side of the ring centre, but the bell-shaped distribution was found basically the same for the centre and the four surrounding measurement points, implying that the short term (1 sec) variability of CO2 concentrations across the MiniFACE ring is almost the same at any point in the ring. Based on gas dispersion simulations and measured CO2 concentration profiles, the possible interference between CO2-enriched and control rings was found to be negligible beyond a centre-to-centre ring distance of 6 m. PMID- 11214347 TI - The importance of leaching from litter collected in litterfall traps. AB - Litterfall (LF) is usually collected by means of open traps. However, this litter will be subject to leaching by the throughfall which passes through the accumulated litter in the traps. The nutrients lost during this leaching are not taken into account in the calculation of LF nutrient fluxes. We report the results from a 2-month (August-September) study carried out in 8 northern coniferous forest stands to assess the possible importance of leaching from litter in LF traps. Compared to throughfall (TF), the litterfall leachate (LFLgross), which includes a throughfall component, had significantly (p < 0.05) higher concentrations and fluxes of Ca, Mg, Na and S. The average net LFL (i.e., LFLnet = LFLgross - TF) fluxes were 21 (Ca), 7 (Mg), 57 (K), 10 (Na), 10 (N), and 19 (S) mg m-2 mo-1. LFLnet accounted for 42%, 37% and 50% of the LFLgross flux, and for 91%, 51% and 49% of the total litterfall flux (i.e., LF + LFLnet) of Na, S and K, respectively. For Ca, Mg and N, the LFLnet flux accounted for 64%, 58% and 29% of the LFLgross flux, and for < 14% of the total litterfall flux. Compared to TF, LF was the dominant return pathway for Ca, Mg and N to the forest floor regardless of whether LFLnet was included or not. However, for K and S, taking LFLnet into account determined whether TF or LF was the dominant pathway. TF remained the dominant pathway for Na even when LFLnet was included. PMID- 11214348 TI - Distribution of heavy metals in surface sediments from an Antarctic marine ecosystem. AB - The concentrations of lead, cadmium, copper, chromium, iron, manganese and zinc in surface sediments collected from Potter Cove, in the 25 de Mayo Island (King George Island), Antarctica, and its drainage basin, were measured by atomic absorption spectroscopy. The obtained results were use to determine the areal and vertical distribution of the metals of in the Cove and potential sources of these metals to this environment. The geochemical data suggest that most of the metals found in Potter Cove constitute a redistribution of autochthonous materials within the ecosystem. Therefore, the metal concentrations can be considered to be present at natural background levels in surface sediments. PMID- 11214349 TI - A watershed-based cumulative risk impact analysis: environmental vulnerability and impact criteria. AB - Swine Concentrated Animal Feeding Operations (CAFOs) have received much attention in recent years. As a result, a watershed-based screening tool, the Cumulative Risk Index Analysis (CRIA), was developed to assess the cumulative impacts of multiple CAFO facilities in a watershed subunit. The CRIA formula calculates an index number based on: 1) the area of one or more facilities compared to the area of the watershed subunit, 2) the average of the environmental vulnerability criteria, and 3) the average of the industry-specific impact criteria. Each vulnerability or impact criterion is ranked on a 1 to 5 scale, with a low rank indicating low environmental vulnerability or impact and a high rank indicating high environmental vulnerability or impact. The individual criterion ranks, as well as the total CRIA score, can be used to focus the environmental analysis and facilitate discussions with industry, public, and other stakeholders in the Agency decision-making process. PMID- 11214350 TI - Assessment of water pollution and suitability to fish life in six Italian rivers. AB - This paper reports the results of a monitoring programme of six rivers (Serchio, Cecina, Cascina, ERa, Elsa and Pavone) that drain north-west Tuscany (Italy). In this area, agricultural, industrial and urbanization pressures affect water quality, also in terms of suitability for the survival of aquatic organisms. The river waters were monitored for several physico-chemical parameters (temperature, dissolved oxygen, suspended solids, total ammonia, nitrites, Cu, Cd, Cr, Ni and Pb) in order to assess the anthropogenic impact on the environmental conditions of these watercourses and their suitability for fish life. Statistical data handling was performed for each river and the percentage of physico-chemical parameters that, according to the E.C. law, were over the limits that must not be exceeded to protect fish life, was calculated and a classification was made of the six rivers in this sense. Concerning the metals, inter-element relationships (between chromium and nichel, lead and copper, nichel and lead and copper, copper and lead) were found which allow some remarks on the origins of the anthropogenic impacts, and comparisons were made with two metal-polluted watercourses in northern Italy, the Po and Lambro rivers. From the comparison, the Tuscan rivers showed generally lower metal contamination, especially with respect to the Lambro. PMID- 11214351 TI - Plasma and breast milk vitamin A as indicators of vitamin A status in pregnant women. AB - Breast milk vitamin A is not well characterized as an indicator of vitamin A status in women with infections. A controlled trial of vitamin A, 3 mg retinol equivalent/day, was conducted among 697 pregnant women with human immunodeficiency virus (HIV) infection in Malawi which allowed comparison of plasma versus breast milk vitamin A as indicators of vitamin A status. Retinol concentrations were measured in plasma at baseline (18-28 weeks) and 38 weeks gestation and breast milk at 6 weeks post-partum. Plasma alpha 1-acid glycoprotein (AGP) and C-reactive protein (CRP) were measured at baseline. Plasma retinol (geometric mean, SD) at 38 weeks was 0.72 (0.44, 1.18) and 0.61 (0.38, 0.98) mumol/L (P < 0.0002) and breast milk retinol was 1.32 (0.71, 2.43) and 0.95 (0.49, 1.82) mumol/L (P < 0.0001) in vitamin A and placebo groups, respectively. Women with elevated acute phase protein (AGP > 1 gm/L and/or CRP > 5 mg/L) at baseline who received vitamin A had significantly higher plasma and breast milk vitamin A at follow-up compared with placebo. Elevated acute phase proteins did not distinguish women with low body stores of vitamin A. Breast milk retinol appears to be a better indicator of vitamin A status than plasma retinol in women with infections. PMID- 11214352 TI - Effects of supplemental vitamin A on retinoic acid concentrations in the plasma of preruminant calves. AB - Neonatal calves are fed frequently milk replacers with vitamin A concentrations exceeding those recommended by the National Research Council. The vitamin A metabolite, retinoic acid (RA), affects profoundly cellular differentiation and homeostasis. For this reason, effects of dietary vitamin A on plasma concentrations of RA isomers in milk replacer-fed calves were examined. Male, Holstein calves (n = 24) were fed colostrum within 12 hours after birth and, thereafter, a custom-formulated low vitamin A milk replacer providing 0, 1700 [National Research Council (NRC) daily requirement for young growing calves] (controls), 34,000 (industry standard in the United States) or 68,000 IU of vitamin A daily. Concentrations of retinol and RA isomers in plasma samples collected from birth to 27 days of age were determined by HPLC. Retinol was affected by dietary vitamin A with higher concentrations occurring in calves supplemented with > or = 34,000 IU of vitamin A/day than in control (1700 IU of vitamin daily) and unsupplemented calves. Relative to controls, concentrations of all isomers of RA were higher in calves supplemented with > or = 34,000 of vitamin A daily during the experimental period. The predominant isomer in all calves was 9,13-dicis-RA. In control calves, 9,13-dicis-RA and 9-cis-RA were maximal at 1 to 6 days of age and then decreased progressively. In calves fed > or = 34,000 IU of vitamin A daily, concentrations of these isomers were markedly higher at 6 days of age, relative to controls, and remained elevated for the duration of the study. In all calves, retinol was correlated positively with 9,13 dicis- and 9-cis-RA from 9 to 27 days of age. 9,13-cis-Retinoic acid was correlated positively with 9-cis- and 13-cis-RA from 13 to 27 days of age. It is concluded that supplementing milk replacer-fed calves with vitamin A at levels exceeding current NRC recommendations by > or = 20-fold causes an elevation in plasma concentrations of retinol and retinoic acids. 9,13-dicis- and 9-cis Retinoic acids were most affected by supplemental vitamin A. Physiologic consequences of increased plasma RA concentrations induced by high dietary levels of vitamin A warrant investigation. PMID- 11214353 TI - Serum parathyroid hormone in healthy Japanese women in relation to serum 25 hydroxyvitamin D. AB - The aim of this work was to clarify levels of serum parathyroid hormone (PTH) in healthy adult women and to study the relationship between PTH and 25 hydroxyvitamin D [25(OH)D]. One hundred sixty-nine healthy women aged 40 years or older in a community were studied. The average age of the subjects was 65.3 years (SD 8.2). All subjects had normal serum creatinine levels. Serum intact PTH and 25(OH)D were measured in these subjects. The mean intact PTH concentration was 2.19 pmol/l (SD 1.02). High intact PTH levels above the reference range were observed in four women (2.4%), all of whom were aged 70 years or older. Intact PTH increased with age with a correlation coefficient of 0.192 (p = 0.013). However, there was no correlation (r = -0.125, p = 0.105) between intact PTH and 25(OH)D whose concentrations were more than 37.5 nmol/l. In conclusion, PTH levels of healthy adult Japanese women are lower than previous reports from Western countries, which may be due to the high 25(OH)D levels of the present subjects and/or an ethnic difference. In addition, there is no association between serum 25(OH)D and PTH levels in this Japanese population, supporting a cutoff level of 25(OH)D less than 37.5 nmol/l for the elevated PTH level. PMID- 11214354 TI - Vitamin E deficiency fails to affect myocardial performance during in vivo ischemia-reperfusion. AB - Vitamin E content of cardiac tissue has been proposed to play a major role in the damage caused by myocardial ischemia-reperfusion (I-R). Previous studies using in vitro models have examined vitamin E deficiency and I-R-induced myocardial damage with equivocal results. The purpose of this study was to use an in vivo model of myocardial I-R to determine the effects of vitamin E deficiency on myocardial I-R induced damage. Female Sprague-Dawley rats (4-mo old) were assigned to either: 1) control diet (CON), or 2) vitamin E deficient diet (VE-DEF). The CON diet was prepared to meet AIN-93M standards, which contains 75 IU vitamin E/kg diet. The VE-DEF diet was the AIN-93M diet prepared with tocopherol stripped corn oil and no vitamin E. Following a 14-week feeding period, significant differences (p < 0.05) existed in mean myocardial VE levels between groups (mean values +/- SEM: CON = 48.2 +/- 3.5; VE-DEF = 12.4 +/- 1.4 micrograms VE/g wet weight). Animals from both experimental groups were subjected to an in vivo I-R protocol consisting of 25 minutes of left coronary artery occlusion followed by 10 minutes of reperfusion. No group differences (p > 0.05) existed in cardiac performance (peak arterial pressure or ventricular work) or the incidence of ventricular arrhythmias during the I-R protocol. VE-DEF animals had significantly higher (p < 0.05) levels of myocardial lipid peroxidation and lower (p < 0.05) protein thiols following I-R compared to the CON animals. These data suggest that although vitamin E deficiency increases oxidative damage resulting from myocardial I-R, it does not affect cardiac performance during the insult. PMID- 11214355 TI - Comparative effects of vitamin K2 and estradiol on experimental arteriosclerosis with diabetes mellitus. AB - In order to further investigate the radical scavenging and anti-arteriosclerotic activities of vitamin K2 and estradiol, the comparative effects of vitamin K2 and estradiol on aortic calcium (Ca) and inorganic phosphorus (P) levels in the aorta and the elastin fraction (fr.) were investigated in male rats after experimental arteriosclerosis with diabetes mellitus was induced by vitamin D2 and radical producing substance, streptozotocin (STZ). Pharmacological dose of vitamin K2 (100 mg/kg b.w.) and medical dose of estradiol (83 micrograms/kg b.w.) suppressed the increased serum glucose, and vitamin K2 and estradiol increased the decrease in serum insulin. Moreover, vitamin K2 and estradiol inhibited the increase of Ca and P in the aorta and the elastin fr. Vitamin K2 and estradiol decreased the increase in serum lipid peroxide (LPO). It is suggested that both the pharmacological dose of vitamin K2 and medical dose of estradiol suppressed the development of arteriosclerosis associated with diabetes mellitus, owing to radical scavenging activity of vitamin K2 and estradiol. PMID- 11214356 TI - Beta-carotene, retinol and alpha-tocopherol status in calves fed the first colostrum at 0-2, 6-7, 12-13 or 24-25 hours after birth. AB - Effects on beta-carotene, retinol and alpha-tocopherol status of feeding 1st colostrum at 0-2, 6-7, 12-13 and 24-25 h after birth were studied in calves. beta carotene, retinol and alpha-tocopherol concentrations decreased in colostrum during the first 2.5 d of lactation. Plasma beta-carotene, retinol and alpha tocopherol concentrations in newborn calves were very low. Plasma beta-carotene concentrations increased up to d 3 after the 1st meal and during the 1st month were higher in calves fed 1st colostrum at < 6-7 h than at > 12-13 h after birth. Plasma retinol concentrations increased up to d 5 after the 1st meal and were higher during the 1st month in calves fed 1st colostrum at < 12-13 h than at > 24 25 h after birth, whereas hepatic concentrations increased up to d 5 independent of time of 1st colostrum feeding. Plasma alpha-tocopherol concentrations increased after the 1st meal except in calves fed 1st colostrum at 24-25 h after birth and were higher during the 1st month in calves fed the 1st colostrum at 6-7 h than at 24-25 h after birth. In conclusion, delaying 1st colostrum intake by more than 12-13 h after birth impaired the plasma beta-carotene, retinol and alpha-tocopherol status during the 1st month of life, but did not negatively influence hepatic retinol concentrations. PMID- 11214357 TI - Bioavailability of water- and lipid-soluble thiamin compounds in broiler chickens. AB - The bioavailability of thiamin mononitrate, thiamin chloride-hydrochloride and benfotiamin was compared in broiler chickens. A thiamin-deficient diet was supplemented with either 1.8 and 1.5 mg/kg thiamin equivalent as water-soluble salts, or with 1.5 and 1.2 mg/kg thiamin equivalent as benfotiamin, respectively, and fed to 3 replicate groups/treatment for 21 days. Weight gain, feed consumption and feed conversion rate were not significantly affected by solubility or dietary level of thiamin. Likewise, using biochemical indices of thiamin status (erythrocyte transketolase activation coefficient, and thiamin concentrations in blood and liver), no differences were found between the water soluble thiamin salts, indicating that they have identical potency. In contrast, biochemical indices of thiamin status showed a significantly higher bioavailability for benfotiamin than for the water-soluble sources. PMID- 11214358 TI - Thiamin status of gravidas treated for gestational diabetes mellitus compared to their neonates at parturition. AB - Since thiamin plays a role in glucose metabolism we wanted to know if blood thiamin influx from gravida to neonate was influenced by treatment of gravidas having gestational diabetes mellitus (GDM). In this study we found thiamin hypovitaminemia in 19% of the 77 pregnancies despite vitamin supplementation and treatment for GDM; neonates born to mothers with hypovitaminemia were also thiamin hypovitaminemic. All neonatal blood had significantly higher thiamin concentration than gravidas. Indeed, cord blood from neonates born to mothers treated with insulin for GDM had significantly higher thiamin concentration than other neonates in the study. A significant weight depression was noted in neonates born to treated GDM mothers. Healthy gravidas giving birth to macrosomia neonates, had significant thiamin hypovitaminosis, but only macrosomic neonates of treated diabetic mothers had significantly depressed blood thiamin concentrations. We noted that subclinical thiamin hypovitaminemia is prominent during pregnancy despite vitamin supplementation. Perhaps increased thiamin supplementation during pregnancy seems warranted to avoid metabolic stress in mother and fetus due to thiamin hypovitaminemia. PMID- 11214359 TI - Lipid peroxidation in nicotinamide-deficient and nicotinamide-supplemented rats. AB - Supplementation or deficiency of nicotinamide in rats may interfere with the oxidative balance, with excess leading to greater lipid peroxidation, measured by TBARS, and deficiency causing a greater consumption of antioxidants such as vitamin E and glutathione. Urinary N-methylnicotinamide excretion was much more marked in the supplemented group, whereas the difference between deficient and control animals was nonsignificant. PMID- 11214360 TI - [Strength training in patients after myocardial infarct]. AB - The objective of the work was to evaluate the suitability and safety of resistance training in patients after myocardial infarction (IM), in older patients and to assess the suitable time for including resistance exercise into the rehabilitation programme. The group comprises a total of 74 patients after IM aged 27-76 years (57 +/- 9). The group included 65 men and 9 women. The authors divided the whole group into two sub-groups by age. The first group is formed by patients under 65 years and the second one by those aged > 65 years. The authors included resistance training from the third week of the rehabilitation programme. During the resistance exercise none of the patients suffered from impaired rhythm or stenocardia. The total muscular strength during the initial tests was in the first group (< 65 years) 105 +/- 26 kg and 93 +/- 26 kg in the group of older patients. At the end of the rehabilitation programme in both groups a statistically significant increase of the total strength was recorded. In the first group it was 120 +/- 20 kg and in the older patients 108 +/- 23 kg, i.e. an increase by 14 and 16%. The mean value of the ejection fraction (EF) was at the onset of rehabilitation 58 +/- 7% and did not differ substantially in the two groups. The mean EF value at the end of rehabilitation was 59 +/- 9% in the first group and 58 +/- 10% in the second group (n.s.). The body weight expressed as the body mass index was initially significantly lower in the older patients (25.5 +/- 2.6 kg/m2 vs. 27.4 +/- 3.3 kg/m2, p < 0.01). During the rehabilitation programme in both groups a slight but statistically significant decline of body weight was recorded. In the first group (< 65 years) to 27.0 +/- 3.2 kg/m2 and in the group of older patients to 25.2 +/- 2.4 kg/m2 (p < 0.01). It can be concluded that the application of resistance exercise as a supplement of classical aerobic training is a suitable, beneficial and safe extension of the regabilitation programme. The use of resistance exercise is suitable even in older patients, it is well tolerated and is not associated with cardiovascular complications. Resistance exercise can be applied already after two weeks of the aerobic programme. PMID- 11214361 TI - [Dehydrdoepiandrosterone, dehydroepiandrosteron-sulfate and insulin in acute myocardial infarct]. AB - The authors discuss the relationship between dehydroepiandsoterone, its sulphate conjugate and insulin and ischaemic heart disease in patients with acute myocardial infarction. In the examined group of patients they found lower values of dehydroepiandosterone and its sulphate in men, lower values of dehydroepiandosterone in women as compared with mean values with regard to age and a close inverse correlation of insulin and dehydroepiandrosterone and insulin and dehydroepiandrosterone sulphate. Whether dehydroepiandosterone is the "missing link" of hyperinsulinaemia and arterosclerosis is so far only a theoretical issue. PMID- 11214362 TI - [Helicobacter pylori and nonspecific intestinal inflammation]. AB - In 50 subjects with non-specific inflammations of the gut the total prevalence of Helicobacter pylori positive antibodies was 28%, while in the control group of blood donors its was 54% Patients with ulcerative colitis had lower antibodies- 18%, in Crohn's disease the serum positivity was 33%. The lowest value of antibodies was found in patients taking Sulfasalazine--11%. The serum positivity was substantially higher in inactive ulcerative colitis and Crohn's disease--35% than in patients with signs of high activity--13%. In 28 patients with non specific inflammations of the gut endoscopy was performed, in 60% with a pathological outcome. Histologically confirmed gastritis was in the majority Helicobacter pylori negative. It may be stated that in patients with non-specific inflammations of the gut there is a lower incidence of Helicobacter pylori than in the general population, in particular those subjects who were or are treated with Sulfasalazine. The explanation of this fact is however only speculative. PMID- 11214363 TI - [The role of ergometric testing in diagnosis of latent long QT syndrome]. AB - BACKGROUND: The long QT syndrome is a genetically determined disease based on mutations of ion membrane channel genes. The resulting prolongation of repolarization increases a risk of malignant ventricular arrhythmias and sudden death. The diagnosis is problematic in individuals with borderline or even normal corrected QT interval value. Ventricular arrhythmias in this syndrome are often provoked by exercise, therefore exercise testing is considered as a useful differential diagnostic method. METHODS: In a 24-member family an occurrence of the long QT syndrome was established clinically in 7 patients. In other 3 members borderline corrected QT interval values were found (0.44-0.46 s). In these individuals a stress testing by bicycle ergometry was performed. RESULTS: During exercise in a 28-year old man (patient III/6) the corrected QT interval prolonged to 0.53 s, in a 27-year old man (patient III/2) and in a 20-year old woman (patient III/9) physiological QT interval shortenings were observed (0.4 s during peak exercise). The diagnosis was confirmed by molecular genetic investigation. In patient III/6 (along with other symptomatic family members) a mutation in exon 7 of KCNQ1 (previously called KVLQT1) gene was found. In patients III/2 and III/9 no signs of KCNQ1 gene pathology were present. CONCLUSIONS: In families with clinically established diagnosis of long QT syndrome occurrence the exercise testing reveals previously asymptomatic individuals, at least in LQT1 type (which is the most common). In general stress testing and measurement of QT interval dynamics is a necessary part of arrhythmological investigation especially in young individuals with history of syncope. PMID- 11214364 TI - [Echocardiography and sonography of the carotid arteries in diabetics with cerebrovascular stroke]. AB - The incidence of cerebrovascular attacks (CVA) in diabetics is 2-3 times higher as compared with the non-diabetic population. The objective of the present work was to evaluate etiological factors by means of echocardiography and sonography of the carotid arteries. The authors evaluated retrospectively findings of these examinations in 253 patients with CVA in a group of diabetic and non-diabetic patients as well as in a group of patients with atrial fibrillations or sinus rhythm. In patients with a sinus rhythm the presence of diabetes was associated with a more frequent finding of atherosclerotic changes, significant stenoses of the carotid vessels (2% as compared with 8%, p < 0.05) as well as thickness of the intima in the carotid bulbus (0.78 as compared with 0.96 mm, p < 0.05). Conversely when evaluating signs of thromboembolic risk, i.e. the size of the left ventricle (42 vs. 40 mm, n.s.) and ejection fraction of the left ventricle (55% vs. 50%, n.s.) no statistical significance in the difference of parameters was found. In the sub-group of patients with atrial fibrillation, who accounted for 28% of the group, the authors did not find when comparing diabetic and non diabetic patients, any difference as regards the presence of significant stenoses in the carotid arteries nor in the thickness of the intima. There was no statistically significant difference in the size of the left atrium and left ventricular function. The findings suggest the possibility that the increased risk of ischaemic CVA in diabetic patients is caused by the atherosclerotic process in the carotid vessels and not a higher risk of embolism of cardiac origin. PMID- 11214365 TI - [Catheter therapy in patients with stable angina pectoris. Results of 662 coronary angioplasties]. AB - Coronary angioplasty supplemented by implantation of a stent has become a standard therapeutic method in patients with stable angina pectoris. The authors analyzed the spectrum of patients indicated for this treatment, its successfulness and complications of catheterizations. In the course of a two-year period the authors implemented 662 catheterizations in 602 patients with stable angina. 58% patients indicated for coronary angioplasty on account of stable angina had a history of myocardial Q infarction, 93% had angina grade II or III according to CCS. Affection of one artery was diagnosed in 56% patients, complete revascularization was achieved in 59% of the operations. The clinical rate of success of catheterization was 97% in stenoses of the coronary arteries and 61% in coronary occlusions. In 57% of the treated lesions a coronary stent was implanted. Serious clinical complications developed in 1% of the interventions, none of the patients died. Catheterization treatment of stable angina is very successful and safe. PMID- 11214366 TI - [Experimental study of resveratrol and flavonoids in red wine with regard to their possible hypolipemic effects]. AB - Resveratrol (trans-3,5,4'-trihydroxystilben) is a polyphenol (phytoalexin) naturally found in wine and different therapeutic plants. It is a substance with an antioxidant and estrogenic effect and the ability to inhibit the growth of some tumours. Some studies mention its possible antiaggregation, neuroprotective and antiallergic effect. In the submitted pilot study the authors investigated the effect of resveratrol and flavonoids (anthocyanins, catechins) on serum lipid levels, in particular total cholesterol and liver enzymes in the laboratory rat. In the experiments healthy animals were used (fed a standard diet) as well as hypercholesterolemic animals (fed a special sugar diet) and treated animals. The investigated parameters were total cholesterol, HDL-cholesterol, aminotransferase aspartate (AST) and alanine aminotransferase (ALT). The conclusions of the investigation indicate that resveratrol and flavonoids (anthocyanins, catechins) found in red wine significantly reduce the total cholesterol level in the hypercholesterolemic rat. The resultant effect of resveratrol and flavonoids on liver enzymes in our experiment is not unequivocal. PMID- 11214367 TI - [Therapy of vasovagal syncope (nonpharmacologic therapy and pharmacotherapy)]. AB - Recurrent vasovagal syncope is a frequent clinical problem. Provisions regarding the regimen, non-pharmacological treatment and pharmacotherapy are the basic principles of management of patients with vasovagal syncope. Regimen provisions involve avoidance of predisposing factors and immediate horizontalization during initial presyncopal manifestations. Endurance training, tilt training, autogenous training and increased intake of salt and fluids are possible ways of non pharmacological treatment. According to the relatively extensive number of published reports on pharmacological treatment of vasovagal syncope four preparations proved effective in randomized placebo controlled trials--atenolol, midodrin, paroxetin and enalapril. The author gives an account of non pharmacological and pharmacological treatment of vasovagal syncope, whereby he concentrates on the validity and clinical importance of different trials. PMID- 11214368 TI - [Therapy of vasovagal syncoope (cardiostimulation therapy)]. AB - Cardiostimulation in used less frequently than pharmacotherapy in the treatment of vasovagal syncope. It proves useful in treatment of vasovagal associated with bradycardia. Cardiostimulation of both cavities is more effective than of one cavity. The optimal cardiostimulation algorithm for treatment of vasovagal syncope which ensures and adequate start of cardiostimulation and has an optimal effect on haemodynamic parameters is still sought. The rate drop response algorithm seems promising. The algorithm was used so far only in one randomized study which was to verify the effect of cardiostimulation in the treatment of vasovagal syncope--Vasovagal Pacemaker Study. The study proved a marked risk reduction of relapses of syncope in highly bradycardia during the tilt test. The Vasovagal Pacemaker Study II with is under way at present compares the effect cardiostimulation and placebo and the effect of cardiostimulation with the rate drop response algorithm. PMID- 11214369 TI - [Clinical characteristics of pulmonary embolism]. AB - Pulmonary embolism is nearly always a complication of deep venous thrombosis. The evaluation of risk factors for venous thromboembolism not only aids diagnosis but also guides decisions about the intensity of prophylactic measures. As both the extent and chronicity of pulmonary vascular obstruction vary widely, pulmonary embolism can produce widely differing clinical pictures. From the clinical, pathophysiological and therapeutical point of view, it is convenient to classify pulmonary embolism into four types: acute minor embolism (dyspnoea with or without pleuritic pain or haemoptysis), acute massive embolism (hemodynamic instability), subacute massive embolism (mimicking heart failure or indolent pneumonia), and chronic thromboembolic pulmonary hypertension (slowly progressing dyspnoea). This classification is of importance not only for the rational diagnosis and differential diagnosis, but also for the institution of adequate therapy. Because the disease has many nonspecific manifestations but no pathognomonic symptoms or signs, it is impossible to prove the diagnosis of pulmonary embolism alone on the basis of clinical presentation. PMID- 11214370 TI - [Diagnosis of pulmonary embolism]. AB - Accurate diagnosis of pulmonary embolism is essential to minimize morbidity and mortality caused by failure to treat when necessary or by inappropriate treatment. Because clinical symptoms and signs are nonspecific, it is impossible to prove the diagnosis solely on clinical grounds. The diagnosis requires high level of suspicion, estimation of the pretest clinical likelihood of embolism, and judicious use of objective investigations (scintigraphy, computed tomography, or angiography) to confirm or refute the suspicion. The choice of tests depends on the availability of these tests, the hemodynamic state of the patient, and the presence of other cardiopulmonary diseases. Despite the availability of most accurate tests, pulmonary embolism will continue to be missed if not first considered by the physician. PMID- 11214371 TI - [Adrenomyeloneuropathy as the cause of Addison's disease]. AB - The authors describe adrenoleukodystrophy and adrenomyeloneuropathy found in one family. This disease is a less frequent cause of Addison's disease, but it is very serious from the prognostic aspect. The authors recommend therefore to examine very long chain fatty acid plasma levels in patients with adrenal insufficiency. PMID- 11214372 TI - Canada's first-ministers' conference: health care without strings. PMID- 11214373 TI - Perilous partnerships: the UN's corporate outreach program. PMID- 11214374 TI - Health inequities in the United States: prospects and solutions. AB - An overview of the role that social determinants of health play in influencing health is provided. Emphasis is on the impact of economic inequality in creating health inequities among Americans. Economic inequality is seen as impacting health in three ways: increasing economic inequality weakens population health by creating poverty; weakening communal social structures that support health such as social and health services; and decreasing social cohesion and civil commitment. Documentation is provided of the growing degree of economic inequality in the USA and complicating issues of racial segregation are considered. Specific recommendations for addressing economic inequality, from USA, British, and Canadian sources, are presented. These recommendations indicate the need to move from epidemiologic research to public health action, from demonstrating the major impact of economic inequality on community health to the development and implementation of specific policies and programs to reverse the continuing increase in economic inequality. PMID- 11214375 TI - Using social indicators to inform community drug and alcohol prevention policy. AB - In recent years, the federal government has begun to require state agencies to allocate drug prevention resources according to the needs of local communities. The methods by which this is to be accomplished have not been described, and most published social indicator studies in the field of drug abuse research have used county-level data which are too insensitive to local needs to be of use in resource allocation decisions. The present study describes a needs assessment in drug abuse prevention in the state of New Jersey using municipal-level social indicator data. In addition, it examines the extent to which the resource allocation of one state prevention agency can be predicted by the municipal-level social indicators. Thirty-six social indicators pertaining to 508 municipalities were used in the study, and data were analyzed using principal component analysis and hierarchical regression analysis. Five factors were extracted from the principal component analysis, two of which clearly describe "high risk" municipalities and one of which clearly describes "low risk" municipalities. The regression analysis showed that these factors explained very little of the variance in the state agency's drug prevention spending. The study shows that social indicators can be used to distinguish between different levels of need for drug prevention services at a municipal level, and that these data can be used to inform decisions concerning resource allocation. PMID- 11214376 TI - The ethics of alternative medicine therapies. AB - It is estimated that 42% of the American public is using some form of alternative medicine, which reflects the changing needs and values in our society. Unfortunately, Western medicine has failed to see alternative medicine as complementary and integrative with conventional medicine. This is due to the fact that there is very little scientific data available regarding the safety, efficacy, optimal dosage and side-effects or interactions of these alternative medicine therapies. Many physicians dismiss a patient's questions concerning alternative medicine because the physician believes it is "quackery," without any proof to support this claim. This violates the patient's right to full disclosure of all possible treatment options and encourages patients to use these therapies without their physician's knowledge. As a result, it is estimated that 46% of those using alternative medicine do so without the supervision of their primary care physicians or alternative medicine practitioners. At the present time there is no regulatory process to ensure the safety and efficacy of these alternative medicine therapies. Manufacturers do not have to prove that their product works, but they must ensure that their product is not harmful. The combination of failure to inform physicians of usage and the possibility of adverse reactions with prescription drugs is placing the lives of many Americans in jeopardy. Ethically, consumers have the right to use alternative medicine therapies as a matter of autonomy, but they also have the duty not to harm themselves. To ensure their safety, alternative medicine therapies must be evaluated in regards to safety and efficacy so that they can be integrated into conventional medicine. The Federal Drug Administration has the ethical responsibility to take the lead in this area. To protect the common good, there is a need to know not only what alternative medicine can do for us but what it can do to us. PMID- 11214377 TI - The greening of engineers: a cross-cultural experience. AB - Experience with a group of mechanical engineering seniors at the University of Colorado led to an informal experiment with engineering students in India. An attempt was made to qualitatively gauge the students' ability to appreciate a worldview different from the standard engineering worldview--that of a mechanical universe. Qualitative differences between organic and mechanical systems were used as a point of discussion. Both groups were found to exhibit distinct thought and behavior patterns which provide important clues for sensitizing engineers to environmental issues in future educational initiatives. Cross-cultural and global dimensions of these initiatives are discussed. PMID- 11214378 TI - "Nature and human values" at the Colorado School of Mines. PMID- 11214379 TI - Engineering education for sustainability: reflections on "the greening of engineers". PMID- 11214380 TI - Overcoming the barriers of insularity. Commentary on: "the greening of engineers: a cross-cultural experience". PMID- 11214381 TI - "Sherry's secret". Case study and commentary on research ethics. PMID- 11214382 TI - Transforming animal species: the case of 'oncomouse'. AB - In this paper I deal with ethical implications arising from animal biotechnology. I analyse some general questions surrounding the production of transgenic animals through a specific case study: the oncomouse. In particular, I explore ethical factors involved in the production of oncomice. This is because biologists genetically modify animals' germ cells and refuse to modify human germ cells. I will underline how the international community has thus far justified this 'ethical difference'. PMID- 11214384 TI - Genes in court. PMID- 11214383 TI - DNA patents and scientific discovery and innovation: assessing benefits and risks. AB - This paper focuses on the question of whether DNA patents help or hinder scientific discovery and innovation. While DNA patents create a wide variety of possible benefits and harms for science and technology, the evidence we have at this point in time supports the conclusion that they will probably promote rather than hamper scientific discovery and innovation. However, since DNA patenting is a relatively recent phenomena and the biotechnology industry is in its infancy, we should continue to gather evidence about the effects of DNA patenting on scientific innovation and discovery as well the economic, social, and legal conditions relating to intellectual property in biotechnology. We should give the free market, the courts, researchers, and patent offices a chance to settle issues related to innovation and discovery, before we seek legislative remedies, since new laws proposed at this point would lack adequate foresight and could do more harm than good. However, we should be open to new laws or regulations on DNA patents if they are required to in order to deal with some of the biases and limitations of the free market. PMID- 11214386 TI - Research practices in need of examination and improvement. PMID- 11214385 TI - The 'redefinition of death' debate: western concepts and western bioethics. AB - Biomedicine is a global enterprise constructed upon the belief in the universality of scientific truths. However, despite huge scientific advances over recent decades it has not been able to formulate a specific and universal definition of death: In fact, in its attempt to redefine death, the concept of death appears to have become immersed in ever increasing vagueness and ambiguity. Even more worrisome is that bioethics, in the form of principlism, is also endeavouring to become a global enterprise by claiming neutrality. It appears that the discourse within both disciplines have similarly manipulated the boundaries of death to include the "dying". This paper argues that the redefinition of death debate in biomedicine reveals a concept of personhood which is profoundly western in origin and which is in accordance to the concept adhered to within principlism. Biomedicine and bioethics do not appear to acknowledge the limitations of their own world view and hence lack an understanding of their applicability and appropriateness in diverse social and cultural contexts; a situation which adds credence to claims as to the hegemonic and imperialistic nature of all such global enterprises. PMID- 11214387 TI - Suppression of scientific research: bahramdipity and nulltiple scientific discoveries. AB - The fairy tale The Three Princes of Serendip can be taken to be allegorical of not only chance discovery (serendipity) but of other aspects of scientific discovery as well. Just as Horace Walpole coined serendipity, so can the term bahramdipity be derived from the tale and defined as the cruel suppression of a serendipitous discovery. Suppressed, unpublished discoveries are designated nulltiples. Several examples are presented to make the case that bahramdipity is an existent aspect of scientific discovery. Other examples of non-ideal scientific research and discovery are provided in order to contrast and clarify the meaning and use of bahramdipity. Additional allegories of scientific discovery are taken from the tale and a hope for the strengthening of scientific integrity is expressed. PMID- 11214388 TI - Current trends in the management of deep venous thrombosis and postthrombotic syndrome. PMID- 11214389 TI - Compliance programs. PMID- 11214390 TI - Pediatrics. 1915. PMID- 11214391 TI - AMA agrees in principle with privacy effort; cautions that "the devil is in the details". PMID- 11214392 TI - Principles of observation medicine. AB - The defining characteristic of emergency medicine is "time," or the acuity of disease presentation. Observation, like resuscitation, involves the management of time-sensitive conditions. In the ED there is a continuum of time-sensitive conditions. This continuum extends from resuscitation on one end to observation on the other. When performed well, observation services have been shown to improve diagnostic accuracy, improve treatment outcomes, decrease costs, and improve patient satisfaction. For the subset of ED patients who would have been inappropriately discharged or unnecessarily admitted, the OU has become a safety net of the ED itself. Like EDs, OUs have progressed from being poorly managed areas of the hospital to the cutting edge of acute health care. The principles developed through past experience and research provide a framework for future developments in emergency medicine. PMID- 11214393 TI - Management of patients with syncope and cardiac arrhythmias in an emergency department observation unit. AB - Syncope is an ideal condition for the emergency observation setting because of its difficulty in diagnosis, many causes, high liability, and variable diagnostic approaches. Hospital admissions can be averted with appropriate patient selection for a short-term observation period. Atrial fibrillation is a common presenting condition in the emergency department. With aggressive management, the appropriately selected patient can have restoration of sinus rhythm and be safely discharged home. PMID- 11214394 TI - Abdominal pain and emergency department evaluation. AB - By approaching the abdominal pain patient in a systematic fashion, the physician can improve his or her performance in evaluating the patient in a safe and efficient manner without extensive or redundant tests. PMID- 11214395 TI - Management of traumatically injured patients in the emergency department observation unit. AB - An EDOU may be an ideal setting for the short-term monitoring and treatment of certain acutely injured patients. The patients choosen for observation, and the diagnostic studies used, will be specific to a particular institution's availability and expertise. Pathways should be developed in conjunction with all services caring for these patients. PMID- 11214396 TI - Emergency department observation for toxicologic exposures. AB - Most toxicologic exposures resolve within 24 hours, yet catastrophic outcomes may occur if patients are directly discharged from the emergency department (ED). These cases are, perhaps, the ideal candidates for observation unit (OU) management. This article reviews the criteria for admission and discharge as well as clinical management strategies in the OU for the most common toxicologic exposures. Special attention is given to the multidisciplinary interactions among the ED physician, the medical toxicologist, the physiatrist, and the specialty laboratory. PMID- 11214397 TI - Asthma therapy in the observation unit. AB - The management of asthma is a commonly encountered clinical problem. There have been major advances in the treatment of asthma, including an increase in the drugs available for treatment, as well as in knowledge of the pathophysiology of the disease. Despite these advances, however, the prevalence, morbidity, and mortality for asthma have shown a disturbing upward trend over the past few decades. Experience with the OU management of asthma has shown many advantages: decreased inpatient hospitalization, better quality of life for patients, higher patient satisfaction, cost-effectiveness, and effective patient care. It is estimated that 60% to 70% of asthmatic patients could be treated in an ED observation unit instead of in an inpatient hospital ward. There is a tremendous opportunity for the OU management of asthma to improve patient care, as well as decrease costs, thereby reducing asthma morbidity and mortality. PMID- 11214398 TI - Management of patients with infectious diseases in an emergency department observation unit. AB - Pneumonia, cellulitis, and pyelonephritis are discussed in this review because they are the most common infections requiring hospital care, and they all have significant death or complication rates and broad differential diagnoses. They also demonstrate many of the considerations that could be applied to other infections appropriate for OU care. Table 11 lists additional infections that are good candidates for OU care. A key to successful OU management of infection is early consultation with the primary care physicians and appropriate specialists when one is setting up the unit, designing its guidelines, and when treating specific patients. Because individual patient outcomes are not predictable, increasing the absolute numbers treated and successfully discharged from observation can necessarily increase the percentage of OU patients that are hospitalized. In essence, a group who would be hospitalized from the ED is transferred to observation status, where most avoid hospital admission. Because some patients fail to respond, develop complications, or demonstrate alternative diagnoses, many troubles can be avoided when the primary care and specialist physicians have collaborated in the observation treatment decisions. These guidelines have been presented as a starting point. It is clear that more research targeted at this group of patients is required to refine current practice. As for everything else in medicine, there is no doubt that many of the specific recommendations made here will become obsolete in no time. PMID- 11214399 TI - Economic issues in observation unit medicine. AB - Emergency department observation units are the rational choice for improving the utilization of health care resources and at the same time improving the quality of patient care. Potential pitfalls can be avoided by flexibility on both the part of the observation unit and the hospital administration staff. The continued growth of observation medicine throughout the country is evidence that most have been successful in designing creative solutions to accommodate this new health service. PMID- 11214400 TI - Observation unit management of heart failure. AB - The acute exacerbation of HF can be treated successfully in the OU. There are significant benefits, such as admission avoidance, decreased 90-day readmissions, and decreased costs. HF requires a comprehensive management program with extensive involvement from a multidisciplinary team committed to improving care for this population, however. PMID- 11214401 TI - Extended emergency care for painful conditions. AB - Painful conditions are a common cause for visits to emergency departments. Appropriate therapy often consists of sedating medications followed by a period of observation that is beneficial in assessing their effect. The cause of abdominal pain is frequently elusive, requiring prolonged testing and re examination. Observation is particularly beneficial in assessing this condition, while certain other painful conditions are not suitable for emergency observation because of the need for prolonged treatment. PMID- 11214402 TI - Pediatric observation medicine. AB - Observing pediatric patients in an OU (whether a pediatric or combined or hybrid unit) has many advantages: better patient care, a decrease in missed diagnoses and acuity, better risk management, decreased malpractice liability, cost effectiveness, increased patient and family satisfaction, and psychosocial benefits. Key principles of observation medicine (purpose, time frame, general patient inclusion and exclusion criteria, administration, CQI, and so forth) are equivalent for pediatric and adult observation patients, but there are important differences. Unique characteristics of pediatric observation patients include specific diagnosis, decreased length of stay, less need for cardiac monitoring, a highly variable admission rate, and a decreased percentage or admission rate to the OU from the ED. Whereas the adult OU is primarily a cardiac-monitoring unit, the pediatric OU is a respiratory and infectious disease unit with a frequent need for an i.v. therapy and hydration. Types of pediatric patients commonly treated in an OU include respiratory illnesses (asthma, croup, bronchiolitis, pneumonia), gastrointestinal disorders (gastroenteritis, abdominal pain), dehydration, infections (fever, cellulitis, lymphangitis, pyelonephritis or UTI), overdoses or poisonings, and seizures. PMID- 11214403 TI - Identification of chest pain patients appropriate for an emergency department observation unit. AB - There are no perfect tests or algorithms to exclude ACI. Because acute coronary occlusion often occurs in patients with low-grade coronary stenosis, the diagnostic goal of a chest pain diagnostic protocol is not to identify patients with CAD, but rather to identify patients who may be safely discharged home without the development of complications such as MI, unstable angina, death, shock, or CHF over the next 1 to 6 months. There is an advantage to evaluating patients at the time of their symptoms. Patients who have a small plaque that is ruptured, leading to intracoronary thrombosis and ischemia, will manifest ischemia on diagnostic testing that could missed in routine outpatient testing when their plaque were stable. The diagnosis and risk stratification of acute coronary ischemia in the ED depends on a careful history and interpretation of the ECG. Multiple regression models using readily available data (e.g., history, physical examination, and ECG) provide the best tools for risk stratification. If one is deciding how to select patients for an EDOU chest pain evaluation, diagnostic tools that have previously been tested and validated in this setting are preferable. These include the Multicenter Chest Pain Study derived tools (i.e., Goldman, Lee), the ACI and ACI-TIPI tools, and sestamibi risk stratification tools. This is not to say that other tools may not play a role at individual institutions. It is probably better to select a consistent approach and evaluate its performance, rather than to allow random variation to dictate practice. The future direction probably will involve standardization of the ED chest pain population. This allows outcome and cost-effectiveness comparative research of various strategies for patients with normal or nondiagnostic ECGs and normal biomarkers. Although this approach allows more precise stratification, the risk will never be zero, meaning that there will never be a substitute for good clinical judgment and close follow-up care. PMID- 11214404 TI - Cardiac markers protocols in a chest pain observation unit. AB - The use of cardiac markers to identify high-risk patients in the observation unit is undeniable. As the literature reviewed here reveals, the history and ECG miss a significant portion of patients with acute cardiac ischemia. It appears that acute MI and some high-risk "unstable angina" observation unit patients can be identified within 6 hours of hospital presentation using a combination of cardiac markers. Testing these patients soon after symptom onset or on arrival in the ED for myoglobin, CK-MB subforms, or CK-MB delta appears to provide the best diagnostic usefulness. For testing later in the clinical course, CK-MB troponin I, or troponin T are of clear diagnostic and prognostic value. The markers currently used are unable to identify the significant subset of patients with "non-AMI" coronary syndromes, however. These patients require further testing with appropriate noninvasive or invasive diagnostic studies. PMID- 11214405 TI - Stress testing for risk stratification of patients with low to moderate probability of acute cardiac ischemia. AB - In summary, this article focused on the use of stress testing to risk-stratify patients at the conclusion of their emergency evaluation for ACI. As discussed, those patients in the probably not ACI category require additional risk stratification prior to discharge. It should be kept in mind that patients in this category are heterogeneous, containing subgroups at both higher and lower risk of ACI and cardiac events. The patients with lower pretest probability for ACI may only need exercise testing in the ED. Patients with higher pretest probability should undergo myocardial perfusion or echocardiographic stress testing to maximize diagnostic and prognostic information. Prognostic information is the key to provocative testing in the ED. Prognostic information is the component that will help emergency physicians identify the patients who may be discharged home safely without having to worry about a 6% annual cardiac death rate and a 10% overall death rate over the next 30 months. Stress testing provides this key prognostic data, and it can be obtained in short-stay chest pain observation units in a safe, timely, and cost-effective fashion. PMID- 11214406 TI - Psychiatric school consultation. An organizing framework and empowering techniques. AB - As the myriad biopsychosocial factors contributing to school success become better understood, opportunities will expand for child psychiatrists to contribute to schools. More collaborative roles with school staff will improve both the individual student's success and also the redefinition of schools as they better address the future needs of their students. Psychiatric consultation, including techniques that empower school staff, will become increasingly valuable. PMID- 11214408 TI - School-based prevention of problem behaviors. AB - Sex and violence are the major sources of morbidity and mortality among American youth. Problem-behavior prevention programs based in schools have been found to be feasible, acceptable, and desirable to school personnel, parents, and students for improving students' health status and educational outcomes. PMID- 11214407 TI - High school consultation. AB - High schools painstakingly plan their academic standards, curricula, instructional approaches, technology, and facilities. Also essential to the vision is a systematic plan for developmental guidance, prevention, at-risk services, intervention, crisis responding, and postvention. The consultant, working in partnership with a caring school staff, can promote safety and well being and reduce risk-taking behaviors so that adolescents can get the most benefit from school experiences. Several protocols have been described that may guide a consultant in helping school personnel. PMID- 11214409 TI - Consultation about violent students. AB - Violence in the schools is a growing problem. Psychiatrists consulting to schools can play an important role in helping school-based professionals with early identification, diagnostic evaluations, program planning, and prevention. They can also serve as educators and child advocates and help to coordinate and to organize a team approach. PMID- 11214410 TI - Emerging models. AB - In all these models, the potential of child psychiatrists and other mental health professionals in decreasing student barriers to learning is promising. While expanding the traditional client service model, child psychiatrists can serve as advocates for identifying student's unmet mental health needs, encourage schools to build capacity for effective responses, be vigilant for quality assurance, develop and initiate new programs that systematically respond to needs of the school community, and provide training opportunities that demystify the psychiatric concepts that can help administrators and teachers. Relatively few child psychiatrists are active in the school setting or have developed a presence in the national movement to provide mental health services in schools. In recognition of the fact that traditional models of psychiatric care such as outpatient clinics and hospital-based programs do not reach many children and adolescents, it is hoped that child psychiatrists will be more motivated to have a more active and rewarding presence in the school setting. Even with the variety of responses to the need for increasing mental health services to children, there are a lot of unanswered questions. With only 8000 child psychiatrists in the United States and 80,000 schools, it is clear that we need to be strategic about how best to utilize our resources. The big question is whether there are predictable and alterable characteristics, mechanisms, and interactive processes that enable high-risk students to attain educational and personal success, despite seemingly poor odds. Emerging models have the potential to begin answering this question. PMID- 11214411 TI - Consultation and therapy in the boarding high school setting. AB - The tasks of a psychiatric consultant in the boarding high school setting are complex and require a particular set of tools. A thorough familiarity and comfort with the psychology and psychopathology of adolescence are necessities. In my view a psychodynamic point of view is most helpful. I have emphasized that students attending boarding schools are different from all other high school students in that they are experiencing a radical and more or less permanent separation from their homes a full developmental epoch earlier than their nonboarding peers. Whether this separation is helpful and growth promoting or traumatic and disruptive needs to be evaluated for each individual whose family seeks psychiatric opinion about such matters. Broad generalization is not possible. What is required is a careful evaluation of the developmental state of the particular teenager and an assessment of the psychologic meaning of the experience in terms of that child's psychic reality. To this formulation I add that a knowledge of the particular boarding schools under consideration, their cultures, mores, personnel, and administrative and academic styles can be of great additional help in making a decision. In addition to their radical and early separation from home, boarding students find themselves integrated into tightly knit school communities, each with its own unique group and institutional dynamics. The best consultation work will include an understanding of what is occurring at the interface between individual and school community. These interactions can be as critical in determining the fate of a boarding student as can be the interactions between a student living at home and interacting with his or her family. Separated from home and emotionally hungry for new objects to replace the ones left behind, the boarding student may have passionate and intense interactions with the institutions and members of the school community. In this article I have provided a recent example (Ted) of such an intense interaction, albeit one with a terrible and tragic outcome. Such anatomies of suicides as the one I have tried to reconstruct in this case can provide a realistic basis for optimism that a future recurrence can be prevented. Another case (Bob, discussed first) illustrated the potential for profound and far reaching positive results of the consultation and treatment processes. PMID- 11214412 TI - Developing school mental health in a rural state. The New Mexico School Mental Health Initiative. AB - Enhancing the effectiveness of intervention in addressing barriers to development and learning requires collaboration among agencies, schools, families, and communities. Inadequate policy support related to any of these matters decreases the likelihood of enhancing intervention effectiveness on a large scale. PMID- 11214413 TI - Psychiatric consultation to schools on remote islands. AB - This article describes psychiatric consultation to schools with a diverse cultural group of youngsters in a geographically unique area. Collaborative aspects among the child psychiatrist, the sponsoring agency, and other community agencies are described. PMID- 11214414 TI - Consultation in the classroom. AB - The advantages of classroom, playground, and hallway observation are that the diagnosing child and adolescent psychiatrist can directly observe the difficulties the child is having. When the psychiatrist is an employee of the school district, there can be easier access and quicker help for challenging students. PMID- 11214415 TI - Opportunities within a large metropolitan school district. AB - As a school district employee, the child psychiatrist can offer valuable school consultations at multiple levels as an "insider." The access to teamwork within the district system is particularly empowering and advantageous. This article outlines the richness and variety of school consultative opportunities within the school district. PMID- 11214416 TI - Consultation to administrators. AB - Mental health specialists can contribute to improvements in children's school experience when they work with administrators to incorporate up-to-date mental health knowledge into educational practice. Effective consultation is not simply a knowledge dissemination exercise. The impact of the consultant's input is determined by how responsive the consultation process is to the needs and assets of faculty, students, and the broader community. PMID- 11214417 TI - The benefits of a clinician consulting in schools of education. AB - A psychiatric clinician was available to lecture and discuss behavior of children and adolescents. Faculty in four schools of education in Los Angeles requested this service. These were (1) a university graduate school teacher training program; (2) a school psychologist training program; (3) an undergraduate education program; and (4) an administrator training program. In the last program, experiences providing mental health consultation to administrators were presented. In the first program, an evaluation was conducted. It emerged that the teachers-in-training were able to feel more permission to see their role as counselor as an appropriate part of the teacher role. Their increased knowledge and understanding of psychopathologic behavior, especially in adolescents, seemed to increase their comfort and ability to handle these behaviors. PMID- 11214418 TI - A retrospective view of school mental health consultation. AB - General principles of mental health consultation as written about by Coleman and Maddux are enumerated. Historically, the refinement of these principles for school consultation was described in detail in the literature by Gerald Caplan and Irving Berlin. Common methods define the consultees' problems as work problems; the consultant views the consultees' difficulties as due to intrapsychic conflicts. Resolution of the consultees' difficulties requires the consultant to use methods that enhance the consultee's self-esteem and indirectly provide the consultee insight into the genesis of his or her problems. Thus, consultees are gradually better able to help the client with his or her difficulties. Training of child psychiatry residents in school consultation historically occurred in three divisions of child psychiatry. Training methods were quite similar. The history of consultation to school administrators at various levels, the issues that emerged, and methods of helping administrators to deal with these problems are elucidated. Special problems in dealing with school consultation on two American Indian reservations, especially that of gaining entrance into the school, are discussed. PMID- 11214419 TI - Mental health consultations in the preschool daycare center. AB - This article explores some of the challenges to children's emotional and social development inherent in the all-day childcare programs for children aged 3 to 5 years. The psychoanalytically oriented child development community has offered ongoing assistance, information, and support to teachers, parents, and children in preschools and preschool daycare sites in a number of communities across the country. The process and results of a long-term preschool daycare consultation are presented. PMID- 11214420 TI - School crisis consultation. AB - School crisis consultations are services necessary to assist school communities recover from disruptions that interfere with a learning environment. Child and adolescent psychiatrists are ideal participants in such consultations owing to their knowledge of child development, familiarity with school systems, family dynamics, stress reactions in children, and crisis intervention skills. The exciting challenge is to tailor a consultation based on a needs assessment, degree of impact of event, and other resources. Every consultation is a unique and stimulating learning experience. Those who develop expertise in this area will be poised to lead future consultation efforts. These consultations are now informed by an increasing body of research on children's stress reactions and various types of interventions. PMID- 11214421 TI - Consultation interactions between special education teachers and child psychiatrists. AB - Characteristics were investigated for 169 special education students referred to a child psychiatrist consultant. There was a common occurrence of learning or language disorders, predominance of attention deficit/hyperactivity disorder, severity and complexity of psychopathology, and undertreatment. The teachers especially asked about diagnosis, behavioral management, and medication and also about issues involving learning and language disorders. PMID- 11214422 TI - Training programs in school consultation. AB - The need to train psychiatrists in school consultation is important to approach mental health and psychosocial concerns from the broad perspective of addressing barriers to learning and promoting healthy development. There is a major national impetus to improve academic achievement and literacy, which can be amplified by addressing the social, emotional, and mental health needs of children and youth. Training in school consultation allows the psychiatrist to better understand a critical institution in each child's life and also provides technical assistance and training to school personnel, which facilitates networking between programs and individuals involved in or interested in school mental health. Each of the described programs approaches consultation from a specific focus that varies in time commitment, placement options, and frequency and order of didactic presentations. There is no conclusive available evidence as to which program is most effective, since such evaluation depends on the overall goals of the consultation program itself. PMID- 11214423 TI - Evaluations of outcome in mental health consultation in schools. AB - Outcome evaluation should be a part of every consultation with before-and-after measurements and a control group, if possible. Unfortunately, these are not often available. Eight examples of outcome evaluations are described, for behavioral (child-centered), consultee-centered, and administrative consultations. Evaluation can be statistical or verbal. Behavioral consultations often can have systemic influences. Comparison is made with outcome in a SBHC. PMID- 11214424 TI - Quantification of venous reflux by means of some duplex scanner and light reflection rheography parameters and its correlation with chronic venous insufficiency symptoms. AB - BACKGROUND: The quantification of venous reflux is rarely made but it is valuable for studying the natural history of CVI, its prognostic implications and the therapy effectiveness. We have evaluated some parameters of chronic venous insufficiency, caused by valvular incompetence, by means of duplex scanner and light reflection rheography searching for a better correlation with the clinical stages of vein disease. METHODS: We have examined 107 patients (35 males, 72 females; aged 22-78, mean 61.5 +/- 14.3) with long saphenous insufficiency in different clinical stages and measured the venous reflux, the reflux duration, the reflux grade, the vein diameter near the saphenofemoral junction with the duplex scanner and the refilling time with the light reflection rheography. The reproducibility of the studied techniques has been determined by examining 20 legs four times each in the same day or on different days. Statistical analysis of the data was performed by means of the variance analysis followed by the Waller-Duncan test. RESULTS: The venous reflux, the venous diameter and the refilling time can easily range between mild and severe insufficiency: reflux is 6.3 +/- 2.5 ml/sec at stage I; 27.5 +/- 10.1 at stage III; venous diameter is 6.04 +/- 1.4 at stage I; 10.6 +/- 2.2 at stage III; refilling time is 23.6 +/- 9.6 at stage I; 5.4 +/- 2.4 at stage III. The reflux time and reflux grade are unable to separate the various CVI stages. CONCLUSIONS: The measurement of venous reflux, venous diameter and refilling time is simple, quick, reproducible; these indices are able to differentiate mild from severe CVI but unable to separate patients at the second stage of the venous disease from those at the third stage and then ineffective in the ulcer risk assessment but the reflux is highly predictable. The ulcer risk is practically absent for reflux < 12 ml/sec; highly probable for reflux > 15 ml/sec (20/46 cases; 43.4%). PMID- 11214425 TI - Elective coronary and valve surgery without blood transfusion in patients treated with recombinant human erythropoietin (epoetin-alpha). AB - BACKGROUND: This study evaluates the real effectiveness of epoetin-alpha associated with ferrous sulphate, in reducing blood transfusion in patients undergoing elective open heart surgery not treated with autologous donation. METHODS: Sixty patients had been divided into 2 groups: group A (30 patients) treated with 525 mg ferrous sulphate three time a day per os for 3 weeks; group B (30 patients) treated with epoetin-alpha 10,000 UI twice a week and 525 mg ferrous sulphate 3 times a day. Grouping of patients has been randomized. In both groups hemoglobin, hematocrit, reticulocytes, iron values, ferritine, transferrine, and serological values, have been evaluated sequentially before treatment, before surgery, day of operation, 1st, 2nd, 3rd, 7th postoperative days and at discharge. RESULTS: In group A 86% patients needed blood transfusion (26 out of 30); in group B only 3% of patients needed blood transfusion (1 patient). One year follow up didn't show side effects related to epoetin-alpha. CONCLUSIONS: This study confirms the real effectiveness of epoetin-alpha in reducing the postoperative need for homologous blood transfusion. No side effects due to epoetin-alpha treatment have been proved. The conclusion is drawn that epoetin-alpha can be used as an alternative to blood transfusion or in association with predeposit and in the treatment of basal anemia. PMID- 11214427 TI - [Type "A" aortic dissection. Surgical technique, caseload, and follow-up]. AB - BACKGROUND: The authors analyse the indications for the various surgical strategies through a retrospective study of the morbility and mortality rates in their own series of cases and during follow-up. METHODS: 107 patients were operated for type A aortic dissection between 1978 and 1998: 69 using a technique performed under moderate hypothermia (Group A) and 38 in deep hypothermia (Group B). All patients who survived from 1978 to 1994 underwent an accurate follow-up. RESULTS: The mortality rate in Group A was 21.7% and 26.3% in Group B. 61.9% patients in Group B presented thrombosis of the false lumen, compared to 30.6% in Group A. Patients with a false perfused lumen underwent re-do surgery in 9.5% compared to 3.5% in those with thrombosed false lumen, and 16.6% showed an aortic dilatation rate of over 5 cm compared to 7.1%. CONCLUSIONS: From an analysis of these data, and in line with the data reported in the literature, although it is impossible lo indicate an ideal surgical strategy for this severe pathology, it is extremely important to achieve thrombosis of the false lumen. PMID- 11214426 TI - Prognostic significance of markers of thrombin generation in the acute and chronic phases of non cardioembolic ischemic stroke. AB - BACKGROUND: Previous studies have shown there is activation of the hemostatic system, with thrombin generation, in the acute phase of stroke. Such an activation has unfavourable effects. It is still not known whether there is also a persistent hypercoagulability state in these patients as well as in subjects affected by acute coronary syndromes. METHODS: To know more about the issue, we measured plasma levels of the prothrombin fragment 1 + 2 (F1 + 2) and the thrombin-antithrombin III complex (TAT) in 40 consecutive patients with first ischemic non-cardioembolic stroke; 16 matched involutive cardiomyopathy patients served as the control group. TATs and F1 + 2 were also assessed six months after the onset of stroke symptoms. RESULTS: At baseline stroke patients had higher values than controls of both F1 + 2 and TAT (F1 + 2: 2.38 +/- 2.30 nmol/l vs 1.20 +/- 0.50; p < 0.03; TAT 16.11 +/- 19.60 ng/ml vs 5.51 +/- 4.29; p < 0.05) and these measurements were not related to the typical acute phase reactants. After 6 months F1 + 2 levels in stroke patients were still higher than controls (F1 + 2: 1.68 +/- 0.80 nmol/l vs 1.20 +/- 0.50; p < 0.05), but there were no differences from the baseline levels of F1 + 2 and TAT. According to survival curves mortality was significantly higher in patients with hypercoagulability (defined as F:1 + 2 and TAT levels more than two standard deviations above the mean). CONCLUSIONS: These data confirm that for stroke patients there is sustained activation of the blood coagulation system like in unstable angina and myocardial infarction these abnormalites may have unfavourable prognostic significance. PMID- 11214428 TI - Primary pulmonary hypertension. AB - Primary Pulmonary Hypertension (PPH) is a rare disease that progressively increases pulmonary arterial pressure and pulmonary vascular resistance to the point of right heart failure, in the absence of secondary causes of the disease. The following specific risk factors that can trigger PPH have been identified and examined: appetite depressant drugs, oral contraceptives and hyperuricaemia. Familial PPH transmitted by an incomplete penetrance dominant autosomic mechanism is responsible for about 6% of PPH cases. Recent research groups have identified the gene responsible for familial PPH. Since pulmonary vasoconstriction is the prime cause of PPH, vasodilation of the pulmonary arterial circulation system (using prostacyclin in the form of epoprostenol or iloprost) is the main aim of treatment. PMID- 11214429 TI - Cardiovascular diseases and nitric oxide in humans. AB - The production of nitric oxide is impaired in patients with clinical and instrumental signs of arteriosclerosis (chronic coronary heart disease, stable and unstable angina, myocardial infarction); the NO deficiency is assessed through the vascular response to the infusion of stimulating (acetycholine) or inhibiting (N-mono-methylarginine) substances upon NO synthesis. Also in hypertensive subjects a weak endothelium-dependent vascular relaxation was documented, but this phenomenon is not constant and is still to be confirmed. In hypercholesterolemic patients a hyporesponsive endothelium-dependent vasodilation has been well documented, lipid lowering agents (drugs, apheresis) improve endothelium function. In heart failure low NO levels are found proportionally to the severity of disease: the expression of No is depressed, but cytokine mediated i NOS expression is enhanced, causing exaggerated amounts of NO and producing myocyte damage or death. Interesting findings indicated NO inhalation as a useful tool for reducing pulmonary hypertension and congestive heart failure. PMID- 11214430 TI - Digital necrosis in a woman over eighty. AB - Chronic vascular disorders of the upper limbs are not frequently encountered in women; in addition, advanced age of onset tends to suggest the presence of common diseases such as arteriosclerosis or microembolization. Nonetheless, diagnosis is not always straightforward and in some cases both-laboratory and instrumental findings can do no more than arouse a diagnostic suspicion. We present a case of acro-localized disorder, which proved difficult to diagnose and which we believe may be attributed to a slowly progressing form of scleroderma of the extremities which, in our case, determined positivity of anticentromere autoantibodies. PMID- 11214431 TI - Different impact of carvedilol and transdermal scopolamine on cardiovascular performance of mild-moderate chronic heart failure patients: evidence of useful effects of scopolamine on tolerance to work load. AB - OBJECTIVES: To verify and compare the effects respectively exercised in chronic heart failure patients by transdermal, slow release scopolamine patch and by the beta and alfa adrenoreceptor blocker carvedilol upon the main indexes derived from maximal cardiopulmonary stress test, as well as from analysis of heart rate variability. METHODS: In each of 14 patients suffering from NYHA class II chronic heart failure, admitted to study, the maximal cardiopulmonary test and heart period power spectrum assessment were performed, firstly during usual therapy, then after 7 days of continuous adjunctive treatment with scopolamine patch, and, finally after 3 months of regular administration of oral carvedilol, added to the basal therapy. The need of time enough to the adaptation of the cardiovascular system against the carvedilol pharmacodynamics, together with the need of slow, progressive dose titration, caused that the onset of therapy with carvedilol was separated from assessment of its effects on ergometric and spectral parameters by an interval period of 3 months. RESULTS: During administration of low doses of scopolamine, the values of VO2max, exercise time and double product were respectively 24 +/- 5.3 ml/kg/min, 12 +/- 3 min and 23630 +/- 3760, and resulted significantly higher than basal (p < 0.05 in all cases) and carvedilol-related readings (p < 0.01 by comparisons with VO2max and double product; p < 0.05 by comparison with exercise time). Again during scopolamine, the total variance, LF and HF powers exhibited the values reported as follows: 1255 msec2 and, respectively, 430 and 250 msec2, thus exceeding significantly the basal levels (p < 0.05 from comparison with total power, p < 0.01 from comparisons with LF and HF bands) as well as the levels reached during adrenergic blockade with carvedilol (LF scopolamine vs LF carvedilol: p < 0.01; total power and HF scopolamine vs corrispective carvedilol values p < 0.05). Compared to the basal findings, the carvedilol induced a significant reduction in VO2max (p < 0.05), double product (p < 0.01), peack of heart rate (p < 0.05) and LF power (p < 0.05), and elicited no significant decreases in exercise time; similarly a weak, not significant surge was product by carvedilol in total and HF powers. CONCLUSIONS: Therefore, in patients with left ventricle asymptomatic dysfunction, the low doses of scopolamine potentiate simultaneously the spontaneous heart rare variability and cardiopulmonary maximal testing; whereas, the carvedilol acts upon LF oscillatory component only, the effects upon total variance and HF band being negligible; moreover, this drug depress the myocardial functional capability; in fact, the carvedilol has been demonstrated to produce a remarkable fall in VO2max, this significant reduction in O2 maximal uptake involving the poor rise in cardiac output during the effort or less effective O2 removal from capillary beds or both. PMID- 11214432 TI - Sonographic assessment of hepatic transplants. AB - Liver transplantation has become a standard treatment for end-stage liver disease, with survival rates for liver transplant patients increasing steadily. Several imaging techniques are used to evaluate patients for possible complications of liver transplantation. This article focuses on the role of ultrasound and color flow and spectral Doppler in evaluating complications such as fluid collections and vascular or biliary obstructions. PMID- 11214433 TI - Doctorally prepared R.T.s: a professional profile. AB - Registered radiologic technologists holding doctoral degrees were surveyed to establish demographic and professional profiles. In addition, the scholarly production of this unique group was quantified by self-reports. A majority of respondents (67%) were not employed in the radiologic sciences and most had not authored journal articles, books or submitted grant proposals. Doctorally prepared technologists reported several professional and personal benefits in earning the degree, including self-fulfillment, respect and advanced occupational opportunities. PMID- 11214434 TI - Nuclear medicine infection imaging. AB - This Directed Reading introduces the reader to basic immunological processes related to infection scintigraphy and describes the radiopharmaceuticals used in this type of imaging. Following a discussion of radiation safety and infection control, the article explains various applications of nuclear medicine for detecting and assessing infection. PMID- 11214435 TI - Benign breast disease. AB - When faced with a suspicious clinical or mammographic finding, patients may be anxious about the possibility of breast cancer. Because many of these findings are benign, clinicians attempt to make a rapid and accurate diagnosis to definitively rule out carcinoma. Imaging plays a key role in diagnostic strategies. This article addresses some of the more common benign breast diseases and their differential diagnosis from malignant breast disease. PMID- 11214436 TI - How computers will change education. PMID- 11214437 TI - Acute epiglottitis. PMID- 11214438 TI - Double take. PMID- 11214439 TI - Expanding boundaries. PMID- 11214440 TI - Electronic medical records. PMID- 11214441 TI - Eco-toxicology: traditional and post-normal interpretations of the Great Lakes Water Quality Agreement. AB - Eco-toxicology is a potentially useful fusing of the two distinct disciplines of ecology and environmental toxicology. However, in applying an ambiguous "ecosystem approach," since the late 1970s, to the implementation of the Great Lakes Water Quality Agreement, there have been difficulties in delimiting the Great Lakes issues to be addressed under the Agreement and in ensuring that general biological resource management and conservation issues are dealt with separately under other existing mandates. There is a priority need for managers involved in the implementation of the Great Lakes Water Quality Agreement to decide whether the purpose remains one of maintaining and restoring Great Lakes water quality or whether it has already been transformed into a broad program to maintain and restore ecosystem integrity throughout the entire Great Lakes basin. Parts of this ambiguity may have arisen as a result of this fusing of ecology and environmental toxicology. PMID- 11214442 TI - Field research for the authorisation of pesticides. AB - On request of the Dutch government a committee of the Health Council of the Netherlands has reviewed the role that results of field research in its broadest sense (i.e., including multi-species toxicity tests in the laboratory, research on model ecosystems et cetera) can play in ecotoxicological risk assessment for the authorisation of pesticides. The Committee believes that field research can provide valuable additional data about the exposure of non-target organisms and the resultant effects at population, community and ecosystem level. However, it frequently is unclear how these data might be used in reaching a decision about authorisation. To solve this problem, it is necessary to specify what is understood by "unacceptable damage". Both more clearly formulated protection goals of the government and a better understanding of the ecological significance of effects are needed to clarify this. Furthermore, the Committee points out that the statistical power of field trials must be sufficient to allow for the detection of changes that might be regarded as ecologically relevant. Finally, it recommends keeping a finger on the pulse in relation to authorised pesticides by monitoring their presence in environmental compartments and by investigating their role in suddenly occurring mortality among conspicuous animal species, such as birds, fish and honeybees. This kind of research forms a safety net for substances that have been wrongly authorised. PMID- 11214443 TI - Effects of endocrine disruptors on prosobranch snails (Mollusca: Gastropoda) in the laboratory. Part I: Bisphenol A and octylphenol as xeno-estrogens. AB - The effects of suspected endocrine disrupting chemicals on freshwater and marine prosobranch species were analysed in laboratory experiments. In this first publication, the responses of the freshwater snail Marisa cornuarietis and of the marine prosobranch Nucella lapillus to the xeno-estrogenic model compounds bisphenol A (BPA) and octylphenol (OP) are presented at nominal concentration ranges between 1 and 100 micrograms/L. Marisa was exposed during 5 months using adult specimens and in a complete life-cycle test for 12 months. In both experiments, the xeno-estrogens induced a complex syndrome of alterations in female Marisa referred to as "superfemales" at the lowest concentrations. Affected specimens were characterised by the formation of additional female organs, an enlargement of the accessory pallial sex glands, gross malformations of the pallial oviduct section resulting in an increased female mortality, and a massive stimulation of oocyte and spawning mass production. The effects of BPA and OP were comparable at the same nominal concentrations. An exposure to OP resulted in inverted U-type concentration response relationships for egg and spawning mass production. Adult Nucella from the field were tested for three months in the laboratory. As in Marisa, superfemales with enlarged accessory pallial sex glands and an enhancement of oocyte production were observed. No oviduct malformations were found probably due to species differences in the gross anatomical structure of the pallial oviduct. A lower percentage of exposed specimens had ripe sperm stored in their vesicula seminalis and additionally male Nucella exhibited a reduced length of penis and prostate gland when compared to the control. Because statistically significant effects were observed at the lowest nominal test concentrations (1 microgram BPA or OP/L), it can be assumed that even lower concentrations may have a negative impact on the snails. The results show that prosobranchs are sensitive to endocrine disruption at environmentally relevant concentrations and that especially M. cornuarietis is a promising candidate for a future organismic invertebrate model to identify endocrine-mimetic test compounds. PMID- 11214445 TI - Metals, boron, and selenium in Neosho Madtom habitats in the Neosho River in Kansas, U.S.A. AB - In 1991 and 1992 we determined the levels of metals, arsenic, boron, and selenium in the Neosho River drainage in southeastern Kansas, the primary habitat for the threatened Neosho madtom (Noturus placidus). We evaluated concentrations in sediments, mussels (Quadrula pustulosa and Q. metanevra), and fish (Percina phoxocephala, Cyprinus carpio, and Ictiobus bubalus) from three sites on the Neosho River and one site on the Cottonwood River. We also evaluated contaminant concentrations in C. carpio composite samples collected by the Kansas Department of Health and Environment (KDHE) at two additional locations on the Neosho River in 1990-92. Sediments were contaminated by lead. Concentrations of selenium, boron, and most metals in mussels were low to normal for biota. Arsenic levels in mussels and fish suggest low-level contamination of biota. Aluminum, barium, manganese and strontium concentrations were much higher in mussels than in fish. Five fish composite samples had cadmium concentrations that indicate chronic deleterious effects on biota. Lead concentrations in six fish samples were elevated. Mercury concentrations in most large fish composites exceeded concentration for protection of animals that might consume them. We believe that reductions in cadmium, lead, and mercury contamination, in particular, would benefit aquatic life in the river. PMID- 11214444 TI - Effects of endocrine disruptors on prosobranch snails (Mollusca: Gastropoda) in the laboratory. Part II: Triphenyltin as a xeno-androgen. AB - In laboratory experiments the effects of suspected endocrine disrupting chemicals on freshwater and marine prosobranch species were analysed. In this second of three publications the responses of the freshwater ramshorn snail Marisa cornuarietis and of two marine prosobranchs (the dogwhelk Nucella lapillus and the netted whelk Hinia reticulata) to the xeno-androgenic model compound triphenyltin (TPT) are presented. Marisa and Nucella were exposed via water (nominal concentrations 5-500 ng TPT-Sn/L) and Hinia via sediments (nominal concentrations 50-500 micrograms TPT-Sn/kg dry wt.) for up to 4 months. Female ramshorn snails but not the two marine species developed imposex in a time and concentration dependent manner (EC10 4 months: 12.3 ng TPT-Sn/L) with a comparable intensity as described for tributyltin. TPT reduced furthermore the fecundity of Marisa at lower concentrations (EC10 4 months: 5.59 ng TPT-Sn/L) with a complete inhibition of spawning at nominal concentrations > or = 250 ng TPT-Sn/L (mean measured +/- SD: > or = 163 +/- 97.0 ng TPT-Sn/L). The extension of the pallial sex organs (penis with accessory structures and prostate gland) of male ramshorn snails and dogwhelks were reduced by up to 25% compared to the control but not in netted whelks. Histopathological analyses for M. cornuarietis and H. reticulata provide evidence for a marked impairment of spermatogenesis (both species) and oogenesis (only netted whelks). The test compound induced a highly significant and concentration independent increase in the incidence of hyperplasia on gills, osphradia and other organs in the mantle cavity of N. lapillus indicating a carcinogenic potential of TPT. The results show that prosobranchs are sensitive to endocrine disruption at environmentally relevant concentrations of TPT. Also, M. cornuarietis is a promising candidate for a future organismic invertebrate system to identify endocrine-mimetic test compounds. PMID- 11214446 TI - On developing bioindicators for human and ecological health. AB - Risk assessors and risk managers generally either examine ecological health (using bioindicators) or human health (using biomarkers of exposure or effect). In this paper we suggest that it is possible and advantageous to develop bioindicators that can be used to assess exposure and effect for both human and non-human receptors. We describe the characteristics of suitable bioindicators for both human and ecological health, using mourning doves (Zenaida macroura), raccoons (Procyon lotor), and bluefish (Pomatomus saltatrix) as examples, and list the general characteristics of other species that would make them useful indicators for assessing both human and ecological health. Bioindicators can be used cross-sectionally to assess the status of ecosystems and risk as well as longitudinally for monitoring changes or evaluating remediation. For both human and ecological risk assessment, there are three sets of characteristics to consider when selecting bioindicators: biological relevance, methodological relevance, and societal relevance. An indicator which fails to fulfill these is not likely to be considered cost-effective and is likely to be abandoned. The indicator should be readily measured and must measure an important range of impacts. For long-term support of a bioindicator, the indicator should be easily understood, and be cost effective. We suggest that bioindicators that can also be used for both ecological and human health risk assessment are optimal. PMID- 11214447 TI - Precipitation and aerosol studies in India. AB - In India, rain water and atmospheric aerosols are observed to be alkaline in nature due to the influence of soil-derived particles which are rich in components like Ca and Mg. These components increase the neutralization potential of rain water and have a greater influence at rural site compared to urban site. However, if there are continuous rains, the concentration of crustal components becomes lower resulting in lower pH of rain water. Unlike the characteristics of rain water on continent, the pH of rain water has been observed to be acidic in all the events over the Indian Ocean during Pre-campaigns of Indian Ocean Experiment (INDOEX). The possible reason for acidic rains over Indian Ocean could be the anthropogenic contribution from continent transported by NE winds coming towards the ocean during this period. PMID- 11214448 TI - Ambient air quality monitoring network design for assessing human health impacts from exposures to airborne contaminants. AB - Existing methods of establishing ambient air quality monitoring networks typically evaluate only parameters related to ambient concentrations of the contaminant(s) of interest such as emission source characteristics, atmospheric transport and dispersion, secondary reactions, deposition characteristics, and local topography. However, adverse health risks from exposures to airborne contaminants are a function of the contaminant and the anatomic and physiologic characteristics of the exposed population. Thus, ambient air quality monitoring networks designed for the protection of public health or for epidemiological studies evaluating adverse health impacts from exposures to ambient air contaminants should account for both contaminant characteristics and human health parameters. A methodology has been established which optimizes ambient air quality monitoring networks for assessments of adverse human health impacts from exposures to airborne contaminants by incorporating human health risk assessment techniques. The use of risk assessment techniques as the basis for designing ambient air quality monitoring networks will help to target limited financial and human resources to evaluate human health risks from exposures to airborne contaminants. PMID- 11214449 TI - Spatio-temporal variations of sulphur dioxide patterns with wind conditions in central Taiwan. AB - Sulphur dioxide (SO2) is one of the main atmospheric pollutants in central Taiwan. This article analyses the SO2 concentration seasonal variations and spatial distribution using data obtained from ten air quality monitoring stations and the Taiwan Weather Bureau. It reveals that SO2 concentration is high in winter and low in summer and that high concentration centers are located south of the Taichung coal-fired power plant, the main source of SO2 emissions in the region. The location of high concentration centers changes with different prevailing winds. SO2 variations due to wind direction are not unique. During short periods, when meteorological conditions are constant, variation in the pollution sources cause variations in the spatial distribution. This has been deduced by appreciation of 'Intervention analysis' to time series of hourly data. PMID- 11214450 TI - Is private health insurance in trouble? PMID- 11214451 TI - Hospital managers of the future--what are their needs? AB - In the course of conducting a review of the international Hospital Management MA course at the Nuffield Institute for Health, Leeds University, the reviewers conducted a survey of international health care trends, especially in developing countries, and considered their implications for hospital and health managers. The demands on managers are becoming more complex and require new expertise in working autonomously, financial planning, organisation development, risk management in physical resource use, and quality of clinical care. The course has been restructured to take account of the identified needs. This article discusses the development needs of hospital managers in the context of changing international health trends, and how they can be met. It arises from a review of the Hospital Management course at Leeds University, which has been restructured to enable managers to meet these challenges. The account may interest not only health management development practitioners, but also hospital managers worldwide who reflect on their working environment, and how to respond to it. PMID- 11214452 TI - [Risk management in hospitals: update and prospect]. AB - Recently introduced in Europe, the concept of risk management is now recognised in hospitals. The end of the 90s was noted in particular for the social emergence of nosocomial risks. Tolerated or accepted in the past as just bad luck, they are no longer acceptable today: hospitals must be safe. If hospitals cannot guarantee the total safety of health care, they must manage as far as possible the risks incurred by the patients within the hospital. Risk management is the insurer's job. It is also a new hospital profession and a future concern to meet tomorrow's ever increasing patient demands for safe health care. PMID- 11214453 TI - A quality approach for conducting training needs assessments in the Ministry of Health, State of Bahrain. AB - In health care organizations around the world, Training Needs Assessments (TNAs) have generally followed a professions-based approach. For example, the training needs of doctors, nurses, each allied health profession, and distinct support staff have been analyzed separately--individualized TNAs conducted for each speciality and functional area. Although a professions-based TNA model can provide useful information to human resource development (HRD) professionals, there are two major drawbacks: (1) it is possible that important training needs might be overlooked because of lack of information sharing among professions and (2) such an approach does not encourage an interdisciplinary, team orientation to service provision. This paper proposes an improved method of conceptualizing TNAs, using an approach that builds on the quality management literature (TQM, CQI, etc.) which stresses the importance of customer- and service-orientations to organizing and measuring organizational and individual performance. PMID- 11214454 TI - [Accreditation: the outcome is worth the time and money]. AB - When the Canadian Council on Health Services Accreditation adopted the Client centered Accreditation Program (CCAP), we had to assess our methods and results and encourage the staff at all levels and the users to be involved. A complete change, considerable benefits: improved staff knowledge of the organisation, support and understanding within the teams, improved training through team meetings, more room for the patients and their families. Is accreditation costly? One cannot put a price on the degree of satisfaction experienced by the staff within a team who listens to their opinions and strives to make the daily routine as rewarding as possible. PMID- 11214456 TI - Children in hospital: a design question. AB - Holistic medicine is the global trend in medical care. It involves not only the highest possible standard of diagnosis and treatment, but also designing the whole experience of being ill and that of hospitalization. In such a frame, planning and designing for children has to be considered in such a way that a child will be helped to withstand the effects of illness, the separation from home and family and the entrance into an unusual, unfamiliar and strange world. Although the wellbeing and happiness of children in hospital is the concern of the nursing staff and of the parents, many other factors have to be satisfied also. A young ill child who has to be treated in hospital has to adjust to a number of environmental and treatment conditions which may be upsetting and may have far-reaching effects. Because of all these, much effort has been made, over the last fifty years, to develop planning and design aspects, which will make a child's life in hospital less unnatural. Furthermore, it will reduce the unavoidable and inevitable discomfort, disease, pain and misery experienced by children. These aspects include avoidance of admission of children into hospital whenever possible, operations on a daily basis, unrestricted visits, encouraging of parents to visit or to stay with their children, the provision of suitable playing facilities, materials, equipment etc. This paper will seek to explore and develop: a change in philosophy in child care, its influence on the various types of facilities, the importance of the family, the psychological needs as design factors such as security, social contacts, personal space, movement, comfort, independence, outdoor spaces and others. Factors relating to design parameters and standards will also be explored. The meaning and importance of scale is highlighted since it is felt that children are not miniature adults, but individuals with their own particular capacities. PMID- 11214457 TI - Health care systems: the emperor has no clothes. AB - Stand-alone hospitals are becoming something of a rarity on the American landscape. While hospital boards have repeatedly voted to form systems in the last 10 to 20 years, they have been just as likely to neglect to identify specific, measurable benefits that a merger would bring to their institution. An even if they did, they frequently discontinued evaluating whether system formation brought the hoped-for benefits, thereby justifying ongoing system participation. It is an incumbent fiduciary obligation to continually ask the question: Does continued participation make sense; that is, are we appropriately exercising stewardship over the hospitals' or system's assets by participating in this system? In a sense, boards are in danger of becoming like the emperor in the children's fairy tale, believing they have done the right thing without taking a hard look at today's reality. PMID- 11214459 TI - Learning lessons. PMID- 11214458 TI - Creating knowledge structures in the pharmaceutical industry: the increasing significance of virtual organisation. AB - This paper explores the specific trend and challenges facing the pharmaceutical industry regarding the exploitation of Internet e-commerce technology and virtual organisation to develop and maintain competitive advantage. There are two important facets of the current trend. One is the rapid development of a complex network of alliances between the established pharmaceutical companies and the specialised biotechnology company start-ups. The other is the rapid growth of internet e-commerce companies dedicated to developing specialised technological platforms for acquiring and selling genetic and biochemical knowledge. The underlying challenge is how big pharmaceutical companies can emulate some of the innovation processes of smaller biotechnology company start-ups, and how they can appropriate and applied new technological knowledge on the development of new drugs. Pharmaceutical companies in order to retain competitive advantage need to continuously monitor all aspects of knowledge management with regard to the R&D and manufacturing process (as well as customer management and marketing). Technological change and organisational restructuring should be aimed at boosting the capacity of large firms to innovate rapidly. PMID- 11214460 TI - Managing technology in developing countries. PMID- 11214461 TI - A clear view of structural glazing. AB - An ideal building skin, which has simplicity, flexibility and planarity, bolted systems provide an efficient barrier against weather ingress and can be designed to be aesthetically pleasing structures. It is an ideal system for roof or wall glazing, since drainage and cleaning is made easy by the totally flush exterior. Many innovative applications of bolted systems can be glazed at only 3-4 degrees from the horizontal, making it a multi-purpose facade solution for building designers. Working together, architect, fenestration engineer, structural engineers and glass manufacturer, make up the facade team and each skill is highly specialised. As our knowledge of facade technology develops with every new building challenge, the most complicated external walls can now be constructed with confidence. PMID- 11214462 TI - Sustainable construction: the next 40 years. PMID- 11214463 TI - Managers and nurses. Going to the devil. PMID- 11214464 TI - Managers and nurses. Level crossings. PMID- 11214465 TI - Managers and nurses. Without prejudice. PMID- 11214466 TI - Care to talk? PMID- 11214467 TI - Fractal self-organization of the molluscan (Mizuhopecten yessoensis) hemolymph cells capable of aggregation in vitro. PMID- 11214468 TI - Soliton-like mode in two-dimensional excitable medium: echo effects induced by collision of excitation waves with local nonconductive medium elements. PMID- 11214469 TI - Low-frequency oscillations of bacteriochlorophyll and coherent dynamics of nuclei in the primary processes of photosynthesis. PMID- 11214470 TI - Spontaneous mobility of a lipid layer in a system composed of three immiscible liquids. PMID- 11214471 TI - Ascorbic acid and nitric oxide production in Escherichia coli. PMID- 11214472 TI - Phenotypic dissociation in an Escherichia coli population. PMID- 11214473 TI - Picosecond absorption spectroscopy of cytochrome c oxidase: excited states and relaxation processes in heme groups of cytochromes a and a3. PMID- 11214474 TI - Mechanisms of vibrational mobility of lipid layer in a thermomechanical oscillator composed of three immiscible liquids. PMID- 11214475 TI - The role of peroxyredoxin in the antioxidant system of respiratory organs. PMID- 11214476 TI - Linkage disequilibrium in MNSs blood group system in population of south Backa. AB - Linkage disequilibrium is a characteristic of MNSs blood group system which performs more frequent association of linked alleles than it is expected in comparison with their allelic frequencies. Measure of linkage disequilibrium is the difference between expected and actual genotypic frequencies which is stated in coefficient of linkage disequilibrium. The purpose of this study was to fortify existence of linkage disequilibrium phenomenon inside MNSs blood group system in population of South Backa in comparison with calculated allelic frequencies. Blood group typing in MNSs system included 1,000 healthy nonrelated persons where allelic frequencies, expected and actual genotype frequencies had been calculated, as well as the differences between them. Results of investigation showed that allele has the highest allelic frequency (0.672), S allele has the lowest frequency (0.33), the highest expected frequencies are calculated for Ms/Ns (Ms/NS) (0.218) and Ms/Ns (0.2235) genotypes, while the actual frequencies are highest for MS/NS (Ms/NS) (0.184), Ms/Ns (0.193) and Ns/Ns (0.153) genotypes. Statistically significant difference between expected and actual genotypic frequencies occurs for Ms/MS and Ns/Ns genotypes, which means that S and M and N and s alleles are more frequently associated and prove the existence of linkage disequilibrium phenomenon in population of South Backa. PMID- 11214478 TI - [Arrhythmogenic right ventricular dysplasia]. AB - INTRODUCTION: Arrhythmogenic right ventricular dysplasia (ARVD), disease of uncertain etiology, is characterized by fibrofatty collections in the right ventricular myocardium, premature ventricular complexes with left bundle branch block (LBBB) morphology, ventricular tachycardia and fibrillation. GOALS: To point out diagnostic methods for this progressive disease and to analyze differential diagnosis and significance of arrhythmogenic right ventricular dysplasia in young, active athletes. RESULTS: Arrhythmogenic right ventricular disease can be asymptomatic or manifested (syncope). It is not uncommon that the first evidence of the disease is ventricular tachycardia/fibrillation or sudden cardiac death. Results of electrocardiography, echocardiography, invasive and other methods can, even after few years, be negative for ARVD. The most significant ECG features are inverese T wave in precordial V1-V3 leads and widened QRS complex (> 120 ms) in V1 lead. Significant echocardiographic features and data obtained by invasive hemodynamic examinations are: dilated right ventricle, left and right ventricular end-diastolic diameter ratio less then 0.5, hypokinetic/akinetic areas involving the wall of the right ventricle, predominantly inferobasal, apical and wall of the left ventricular outflow tract. Findings may also include deep fissures among hypertrophied trabeculae. Biopsy may reveal fibrofatty tissue in hypo/akinetic regions of the right ventricular myocardium. DISCUSSION AND CONCLUSION: Since arrhythmogenic right ventricular dysplasia is diagnosed in predominantly young population, not uncommonly athletes, and since it may be cause of sudden cardiac death, there must be a high degree of suspicion in cases with activity related VT/VF and positive family history (it is proposed that it is a hereditary disease). PMID- 11214479 TI - [The modern approach to wound treatment]. AB - INTRODUCTION: Wound healing is a complex process involving interactions among a variety of different cell types. The normal wound repair process consists of three phases--inflammation, proliferation, and remodeling that occur in a predictable series of cellular and biochemical events. Wounds are classified according to various criteria: etiology, lasting, morphological characteristics, communications with solid or hollow organs, the degree of contamination. In the last few years many authors use the Color Code Concept, which classifies wounds as red, yellow and black wounds. This paper presents conventional methods of local wound treatment (mechanical cleansing, disinfection with antiseptic solutions, wound debridement--surgical, biological and autolytic; wound closure, topical antibiotic treatment, dressing), as well as general measures (sedation, antitetanous and antibiotic protection, preoperative evaluation and correction of malnutrition, vasoconstriction, hyperglycemia and steroid use, appropriate surgical technique, and postoperative prevention of vasoconstriction through pain relief, warming and adequate volume resuscitation). THE ROLE OF PHYSIOLOGICAL FACTORS AND ANTIMICROBIAL AGENTS IN WOUND HEALING: Growth factors play a role in cell division, migration, differentiation, protein expression, enzyme production and have a potential ability to heal wounds by stimulating angiogenesis and cellular proliferation, affecting the production and the degradation of the extracellular matrix, and by being chemotactic for inflammatory cells and fibroblasts. There are seven major families of growth factors: epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), interleukins (ILs), and colony-stimulating factor (CSF). Acute wounds contain many growth factors that play a crucial role in the initial phases of wound healing. The events of early wound healing reflect a finely balanced environment leading to uncomplicated and rapid wound healing. Chronic wounds, for many reasons, have lost this fine balance. Multiple studies have evaluated the effect that exogenously applied growth factors have on the healing of chronic wounds. In the study conducted by Knighton and colleagues, topical application of mixture of various growth factors (PDGF, TGF-beta, PDAF, PF4, PDEGF) demonstrated increased wound healing over controls. Brown and associates demonstrated a decrease in skin graft donor site healing time of 1 day using topically applied EGF. Herndon and ass. used systemic growth hormone in burned children and reduction in healing time made a significant clinical difference by allowing earlier wound coverage and decreasing the duration of hospitalization. The TGF family of growth factors is believed to be primarily responsible for excessive scar formation, especially the beta 1 and beta 2 isoforms. TGF-beta 3 isoform has recently been described and may have an inhibitory function on scar formation by being a natural antagonist to the TGF-beta 1 and TGF-beta 2 isoforms. Cytokines, especially interferon-alpha (INF-alpha), INF-alpha, and INF-alpha 2b, may also reduce scar formation. These cytokines decrease the proliferation rate of fibroblasts and reduce the rate of collagen and fibronectin synthesis by reducing the production of mRNA. Expression of nitric oxide synthase (NOS) and heat shock proteins (HSP) have an important role in wound healing, as well as trace elements (zinc, copper, manganese). Applications of some drugs (antioxidants- asiaticoside, vitamin E and ascorbic acid; calcium D-pantothenate, exogenous fibronectin; antileprosy drugs--oil of hydnocarpus; alcoholic extract of yeast) accelerate wound healing. Thymic peptide thymosin beta 4 (T beta 4R) topically applicated, increases collagen deposition and angiogenesis and stimulates keratinocyte migration. Thymosin alpha 1 (T alpha 1R), peptide isolated from the thymus, is a potent chemoattractant which accelerates angiogenesis and wound healing. On the contrary, steroid drugs, hemorrhage and denervation of wounds have negative effect on the healing process. PMID- 11214477 TI - [Therapeutic approach and results in the treatment of subglottic tracheal stenosis]. AB - INTRODUCTION: We had the opportunity to treat upper respiratory tract stenosis, so the aim of this paper was to present results of treatment of subglottic and upper tracheal stenosis in our clinical material. MATERIAL AND METHODS: Retrospective study included a period of 5 years (1990-1995), and evaluated results of treating 11 patients with subglottic laryngeal stenosis--with stenosis of proximal tracheal part. There were 6 females and 5 males ranging from 2-65 years of age. Nine patients had postintubational stenosis, one patient had corrosive injury, and one had congenital stenosis which occurred in older age. Apart from two patients, the rest were already treated in other institutions in our country (1-6 times) where they underwent laser (6 patients) or open surgical resection (3 patients). Diagnosis of stenosis was based on laryngotracheoscopy, laryngotracheal tomography, and CT. RESULTS: The patient with congenital subglottic stenosis underwent resection with laryngomicroscopy. Two weeks later, she was decannulated, having good breathing and voice. Two youngest patients, aged 2 and 10 years, underwent dilatation of upper tracheal part and subglottic stenosis, followed by Montgomery T tube placement. The two-years-old boy had the tube for 26 months. During that period, his tube was once replaced with wider one, and after that, he was decannulated. He has a good voice with preserved mobility of vocal cords, but he still has stenosed subglottic level, which partly narrows the lumen, so his tracheotomy is still present. We successfully decannulated a 10-year-old boy, who had the tube for 18 months after stenosis dilatation. In eight patients stenosis of proximal tracheal part and subglottic part of larynx was diagnosed. It was 2.5 to 4 cm long. In three patients we diagnosed tracheal malacia, and in one of them also cricoid malacia with luxation of one arytenoid and ankylosis of the other. In all patients we performed resection of proximal tracheal part with excision of half of cricoid ring. What was left of laryngeal stenosis was cut out and covered with distal tracheal mucosa or Thiersch grafting. In two patients after resection of proximal part of the trachea and part of cricoid ring, end-to-end anastomosis was performed without tube placing, with excellent results. In six patients Montgomery T tube was placed, and in four of them it stayed for 6 to 12 months. These four patients were later decannulated with good functional results. In the rest of two patients, we did not resolve the stenosis of proximal part of trachea and subglottic space of the larynx. DISCUSSION: In etiology of chronic subglottic stenosis postintubational stenoses are dominate. Methods we used were successful in solving high tracheal and subglottic stenosis if the stenotic part was at cricoid level. In higher subglottic stenosis, other techniques are to be used. CONCLUSION: We presented cases of 11 patients with high tracheal and/or subglottic laryngeal stenosis. In one patient stenosis was solved by laryngomicroscopy, in two with subglottic stenosis dilatation. Eight patients were operated using segmental resection of proximal tracheal part and part of cricoid ring, using end-to-end method. In our opinion this method gives good results in stenosis which does not spread higher than upper cricoid cartilage. Some patients can be operated without tracheotomy. For higher stenoses, this method is not recommended. PMID- 11214480 TI - [What do we know today about diaminodiphenylsulfone?]. AB - INTRODUCTION: Diaminodiphenylsulfone or dapsone is a chemical analogue of sulfapyridine, synthesized in 1908. Dapsone is a bacteriostatic agent that proved to be efficient in treating leprosy and malaria, but today it is used in treating dermatologic noninfectious inflammatory diseases. PHARMACOLOGY: Dapsone is orally used in a dose of 50-400 mg per day in treatment of dermatologic diseases, and also in a dose of 50-100 mg per day in leprosy treatment. Dapsone is mainly eliminated from the body by urine and smaller part by faeces. Pharmacological interaction was reported when it is used with rifampicin and probenecid. MECHANISM OF ACTION: The bacteriostatic effect of dapsone is well known. It involves inhibition of folic acid synthesis in susceptible organisms. The anti inflammatory effect of dapsone, which proves to be efficient in treating noninfectious inflammatory diseases, has not been explained completely yet. There are some pieces of evidence that anti-inflammatory action is not connected with its antibacteriological action. CLINICAL USE: Based on previous studies about therapy efficiency of dapsone in treating some diseases, there are two groups of diseases: the group responding well to dapsone (leprosy, malaria, DH, linear IgA dermatosis, erythema elevatum diutinum, bullous systemic lupus erythematosus) and a group responding with average good response to dapsone (pyoderma gangrenosum, bullous and cicatricial pemphigoid, acne conglobata, discoid cutaneous lupus erythematosus, subcorneal pustulosis dermatosis, granuloma faciale, rheumatoid arthritis, polychondritis, leucocytoclastic vasculitis). ADVERSE EFFECTS: Adverse effects depend on the dose and they rarely occur at doses less than 100 mg per day. They are mainly shown on skin, nervous system, digestive system, hepatobiliary system, and kidney and hematologic system. The most important adverse effects are hemolytic anaemia and methemoglobinemia. Hemolysis usually occurs at doses of 200 mg and more per day. In patients with glucose-6-phosphate dehydrogenase deficiency, hemolysis may be provoked by a dose less than 50 mg per day. For prevention, before using dapsone in therapy, clinical examination with history, blood parameters, liver and renal parameters and determination of glucose-6-phosphate dehydrogenase level are recommended. CONCLUSION: The use of dapsone is absolutely indicated in DH treatment and erythema elevatum diutinum. Because of anti-inflammatory effects, dapsone can also be used in treating other inflammatory noninfectious dermatoses when one should take care about "therapy efficiency/adverse effect" balance using the correct dose, monitoring relevant clinical and laboratory parameters and educating patients. PMID- 11214481 TI - [Late results of myocardial revascularization in patients with coronary artery endarterectomy]. AB - INTRODUCTION: The aim of this study was to evaluate long-term results after myocardial revascularization in patients with diffuse and distal coronary disease, and to compare this procedure with the classical approach--indirect myocardial revascularization (revascularization without endarterectomy). MATERIAL AND METHODS: This retrospective study was done in the period of three years, and includes patients operated between January 1, 1985 and December 31, 1990 at the University Clinic of Cardiovascular Surgery, Novi Sad. 500 patients were included and two groups were made. The investigated group consisted of 251 patients with endarterectomy and control group of 249 patients without endarterectomy. Other parameters (age, gender, preoperative hemodynamic parameters etc.) were practically the same. RESULTS: Postoperative mortality (PM) during immediate 30 postoperative days was 4.64% in the investigated group, and 1.97% in the control group (total PM = 2.66%). The main causes of death were cardiac (3.74%), and the rest of them were respiratory, renal and cerebral. The highest postoperative mortality according to the localization of endarterectomy was left artery descendent (LAD) in the position of the first septal artery (36.36%). The follow up study included 500 operated patients. The mean follow-up period was 9 years (0 13 years). Cumulative survival curve and postoperative myocardial infarction curve made by Wilcocxon (Gehan) and Kaplan-Meier methods showed no statistically significant difference between groups after 13 years of follow up. Lower incident of new angina was found in the investigated group (p < 0.01). Most of patients show good physical condition, well toleration of the stress test (Bruce protocol) and no significant impairment of ejection fraction. DISCUSSION: Despite its long history and development, endarterectomy of coronary arteries is one of the most controversial methods in cardiac surgery. Application of this method was very restrictive mostly because its complexity and very controversial results from one institution to another. Endarterectomy of the first septal artery has the highest operative risk, but it is the method of choice in full revascularization of this region. Despite higher operative mortality, the immediate and long term results of this study show that endarterectomy of the coronary arteries is a method with very acceptable operative risk. CONCLUSION: Endarterectomy is a good and effective method for direct myocardial revascularization in cases with diffuse coronary disease. It is the best procedure for revascularization of the septum. The number of endarterectomies and low ejection fraction are independent predictors for early and long-term mortality. Endarterectomy is also a method of choice in patients with low ejection fraction and poor coronary bed. Frequent and repeated application of angioplasty, higher incidence of diffuse and distal coronary disease and no available donors for heart transplantation will increase the application of this method. In the future we expect further improvement and complete affirmation of endartrectomy of coronary arteries. PMID- 11214482 TI - [Premalignant and malignant lesions of the uterine cervix--personal experience]. AB - INTRODUCTION: Cervical pathology represents the most frequent cause of mortality and morbidity in regard to female genital diseases in Serbia. The aim of this study was to establish the occurrence and grade of histopathologic lesions by examination of cervical biopsy specimens taking into consideration the patient's age and knife conization as a diagnostic-therapeutic procedure. The study included a period of 1993-1997 at the Department of Gynecology and Obstetrics of the Health Center in Sremska Mitrovica. MATERIAL AND METHODS: Criteria for biopsy were: colposcopic or naked eye evaluation of lesions and Papanicolaou smear grade III or higher. Conization was not performed in cases with: low grade squamous intra-epithelial lesion (L-SIL) with HPV (human papillomavirus) and high grade squamous intra-epithelial lesion (H-SIL) or microinvasive Ca (< 5 mm without distribution by lymph or blood). None of the patients had undergone biopsy before. RESULTS AND DISCUSSION: Our results show high occurrence of malignancy, mainly of invasive type. In elder patients all grades of pathologic lesions were established, whereas knife conization showed high efficacy. Although patients might be exposed to risk factors predominantly in their older age, it is evident that public knowledge is poor, while physician-patient relationship is unsatisfactory. CONCLUSION: In accordance with reported, it can be concluded that there is a great need for public health education as well as improvement of secondary health care in the long run. PMID- 11214483 TI - [Cardiovascular disease risk factors in product quality control workers at the AD Neoplant facility in Novi Sad]. AB - INTRODUCTION: Monitoring the health status of the employed in the meat industry "Neoplanta", a high prevalence of cardiovascular risk factors was observed. It was also observed that workers employed in the meat industry have specific dietary habits as a result of working practice. Their hypercaloric diet is with high dietary animal fat and protein intake. This particularly refers to the group of workers in charge of the quality control of meat products who, besides regular hot meal and frequent business lunches, consume certain quantities of these products on a daily basis. A common characteristic shared by members of this group is that they very seldom or never have preventive medical examination. OBJECTIVE: The objective of this paper was to determine cardiovascular risk factors in this group of workers and to evaluate educational program effects on the prevalence of risk factors. MATERIAL AND METHODS: Cardiovascular risk factors were examined in 39 workers (28 men and 11 women) involved in the daily control of meat products and performing executive jobs of different complexity levels in the meat industry "Neoplanta". Cardiovascular risks and lipid status were examined before and after a nine-month-long educational program. Occurrence of increased risks and lipid status elements were tested, p < 0.05. RESULTS: According to obtained results hypercholesterolemia is present in 94.87%, obesity in 82.05%, positive family cardiovascular anamnesis in 74.48%, physical inactivity in 69.33%, continuous alcohol consumption in 69.23%, excessive consumption of black coffee in 61.54%, hypertension in 51.28%, "stress alleviation" with food in 46.15%, hypertriglyceridemia in 46.15% and cigarette smoking in 46.15% of examinees. Cigarette smoking, chi 2 = 1.85, alcohol consumption, chi 2 = 0.26, black coffee drinking, chi 2 = 0.22, preparation of the meals on the fat, chi 2 = 0.10 has remained unchanged after educational program. The number of patients "alleviating" stress with food, chi 2 = 5.26 and physically inactive patients, chi 2 = 1.06 has significantly increased. Body mass, chi 2 = 0.06 and hypertension, chi 2 = 1.42, has not reduced, hyperholesterolemia has remained unchanged, chi 2 = 2.22, LDL-cholesterol has decreased insignificantly, chi 2 = 0.60, while HDL-cholesterol has decreased significantly, chi 2 = 4.27. Atherosclerosis index has increased significantly, chi 2 = 4.47. Thus, poor effects of the educational program can be attributed to unchanged lifestyle habits of the examined workers. CONCLUSION: It can be concluded that cardiovascular risk factors as well as lipid status elements have not decreased in this group of workers after educational program and therefore continuous medical educational program is suggested with purpose to increase the motivation of workers. PMID- 11214484 TI - [The CO2 laser and verruca vulgaris]. AB - INTRODUCTION: Verruca vulgaris, or a common wart, is a benign epithelial contagious tumour. It is usually flesh-coloured hyperkeratotic papule of a small size (few millimetres in diameter) although sometimes it may reach up to 2 cm in diameter. Milder, more conservative chemical therapy often requires weeks or months and is often unsuccessful. More aggressive therapy (e.g. electrodesiccation and curettage) may result in significant morbidity, tissue damage, and scarring. Plantar warts are particularly problematic. CO2 laser has numerous applications in dermatology and dermatologic surgery. It is versatile, being either a vaporising tool or a light scalpel. CO2 laser is an excellent modality for treating problematic or recurrent warts. In our experience it has now become the method of choice for warts. The aim of the present investigation was to evaluate the efficacy of the laser treatment in comparison to more conventional forms of treatment. MATERIAL AND METHODS: Surgical laser was used at 15 W power at superpulsating, pulsating and continuous beam. The wavelength was 10,600 nm and the laser was used at infrared spectrum. Active substance was CO2 in combination with nitrogen and helium at following proportion: CO2:N2:He = 4.5%:13.5%:82%. It was used under the pressure of 20-80 mbars. Lesions are treated with laser in a focused mode at low to medium-power density in a series of brief pulses (0.05-0.1 sec). Treatment was carried out under magnified vision (2.5x magnifying loupes) in order to see all small satellite warts and to judge more precisely when all wart tissue has been vaporized. All interventions were performed under local anaesthesia with either carticaine-chloride or 2% lidocaine chloride. All interventions were performed between 1992-1996 in an outpatient clinic. Warts were excised with a combination of vaporization and resection of the wart root. RESULTS: The laser beam promptly sterilized the operative field more efficiently than any other commonly used disinfectant. Healing was by granulation and the post-operative period was relatively painless for the patient. Healing resulted in either no scar or a supple flexible scar which was asymptomatic. DISCUSSION: Verruca vulgaris most often occurs on fingers and hands of children and teenagers (most commonly between ages 18 to 20). Resistance to therapy is common, and recurrences are frequent. Carbon dioxide laser is a high precision, bloodless light scalpel used for incising and excising tissues with sealing of small blood vessels. It is the treatment of choice for local destruction of intraephithelial neoplastic lesions. The carbon dioxide beam may be used to remove tissue in one of two ways. First, the lesion may be vaporized until a bed of healthy tissue is reached. The second and better technique is to use the beam as a scalpel to excise a lesion with appropriate margins. Post operative morbidity and complications are low, and long-term results appear to be excellent. CONCLUSION: Laser therapy of common warts is a novel form of treatment of these papillomavirus-induced skin tumours. Our results show that this method has numerous advantages over more conventional forms of treatment. PMID- 11214485 TI - [Postpartum anemia--incidence and etiology]. AB - INTRODUCTION: Anemia is the most common puerperal complication which increases the risk of maternal morbidity in postpartal period with incidence of up to 56% of women. In 90% cases the etiology of postpartal anemia is decreased serum iron level. Postpartal hemorrhage (loss of blood more than 0.5 L during labor) is the cause of anemia in 5-10% of women. MATERIAL AND METHODS: This prospective study included 4009 postpartal women with normal pregnancy and delivery who gave birth during the year 1997 at our Department. There were 3305 women with vaginal delivery and 704 women who had cesarean section. Anemia was diagnosed when the hemoglobin serum concentrations were less than 100 g/L (6.21 mmol/L) and hematocrit less than 0.31. RESULTS AND DISCUSSION: Although about three quarters of pregnant women had 8 and more obstetrical controls and 3 and more ultrasound examinations during pregnancy, only half of them had blood count control 3 or more times. Blood count was checked 3 or more times during pregnancy in 54.98% women and 32.9% of all women took iron medication during pregnancy but no longer than 12 weeks. Before pregnancy 0.6% of women had anemia, and after the delivery that number increased to 25.41% with no significant differences between those who had vaginal delivery and those with cesarean section. The incidence of newborns with anemia was 5.11% in both groups. These results show that anemia of mother has no influence on anemia of the newborn who has its own mechanisms of compensation. The etiology of puerperal anemia was in 79.18% women caused by low serum iron levels with no differences between both groups, but infection caused anemia was more frequent in women with cesarean section (11.8%) than in women with vaginal delivery (0.36%). CONCLUSION: Although one third of pregnant women take iron medication during pregnancy, every third woman has anemia after delivery, both vaginal delivery and cesarean section. Women who had cesarean section had anemia more frequently caused by infection. Anemia is 5 times more frequent in the mother than in her newborn. Prophylactic iron medications during pregnancy are not recommended, but more frequent control of blood count during pregnancy is required, as well as adequate therapy of anemia. PMID- 11214486 TI - [Acute meningococcemia in a 4-month-old infant]. AB - INTRODUCTION: What causes meningococcial diseases (MD) is a Gramm-negative diplococcus Neisseria meningitidis (meningococcus). Most frequently it manifests itself in the form of meningitis and meningococcemia. The mortality rate of those suffering from MD has not significantly changed for three decades and ranges from 7% to 19%, and for meningococcemia from 18% to 53%. According to the data presented by domestic authors, of the total of the diseased with bacterial meningitis 75% are children with mortality rate from 6% to 15%. Severe forms of meningococcemia sometimes have extremely rapid development and lethal outcome within a few hours. Key elements for establishing the diagnosis of meningococcemia are presence of hemorrhagic rash with high fever, loss of interest in the environment, loss of consciousness and paleness. CASE REPORT: The boy was admitted to hospital as an emergency case on 29 December 1988 at 11:45. The disease manifested abruptly the day before. He burst into tears easily, would take very little food and in the evening his temperature rose T degree 40.8 degrees C. Before midnight, in the village he was given injections of: lincomycin 300 mg and lasdol 250 i.m. During admittance the infant was agitated, kept moaning. His skin was pail gray with dot-like and spot-like hematoma which were more numerous and intense on the left ear, lower part of the body, scrotum and legs. The infant breathed heavily and fast (FR: 100/min) Cardiologist's finding showed: tahicardia over 200/min, buffled tones, gallop rhythm, pulsating neck veins and edema point to acute heart failure. Large fontanelles remained swollen even after lumbar puncture (LP) and extraction of 15 ml of clear cerebro-spinal fluid. Soon after admittance the boy stopped moaning but didn't cry when pricked and slipped deeper into coma. During the third hour of treatment generalized convulsions began which lasted approximately 10 minutes and stopped after i.v. administered diazepam. The boy remained in coma the second day in lethargy and with swollen fontanelles on the third day, so the first subdural puncture was then performed bilaterally. On that occasion only from the right side 8 ml of reddish liquid was obtained. Right after he was admitted we began permanent transfusion, which lasted 17 days. On the first day he received fresh blood transfusion. He was administered benzinpenicilline, chloramphenicol-succinate, lanatoside, human albumins, dexamethasone.... Blood oxygenation was carried out in the first few days of illness during the exhibited cardio-respiratory failure. DISCUSSION: Among risk factors, which contribute to occurrence of meningococcemia, is also artificial infant food. The reported boy was incorrectly fed with overdiluted cow milk. That and apparent hemostasis brake-down only worsened anemia and increased susceptibility to infections. Although LP was performed when the boy was admitted and the nutritious foundation was soaked with cerebro-spinal fluid, no bacteria were isolated or their presence confirmed in cerebro-spinal fluid colored after Gramm's method, because the child was given linkomycin the previous night. CONCLUSION: On the basis of clinical findings, hemorrhagic rush, convulsions, coma and acute heart failure as well as the laboratory findings it was concluded that it was a case of severe meningococcemia, meningitis and subdural effusion. Listed therapy and six subdural punctures led to full recovery of the patient. Further examination by a pediatrician and a psychologist eliminated the possibility of mental deficiency. The boy is now a good fifth grade elementary school pupil. PMID- 11214487 TI - [Importance of self-assessment of functional and communication abilities on the outcome of rehabilitation in patients with hemiplegia after cerebrovascular stroke]. AB - INTRODUCTION: Cerebrovascular insult causes focal damage of the central nervous system structures consequently causing loss or disturbance of their functions. Motor deficit is often associated with personality alterations generally speaking, as well as changes in behavior and loss of numerous neuropsychological functions. Rehabilitation of such patients should be defined by all members of the team, including the patient himself and members of his family. MATERIAL AND METHODS: This is a case report on a male patient 49 years of age with rightsided paralysis accompanied by aphasia. Thirty days after cerebrovascular insult he was transferred from the Clinic of Neurology in Novi Sad to the Clinic of Medical Rehabilitation. Functional disability assessment was made using Barthel Index, whereas communication was assessed by Boston Diagnostic Aphasia Examination. The rehabilitation program included, apart from the usual team, the patient himself and members of his family. The patient became the center of the team and was informed about the disease. Personal assessment of the patient on his functional and communication abilities and their importance for further progress was used to set the objectives of the rehabilitation program. The rehabilitation program was performed by a speech therapist and a psychologist, including kinesis, work activities, occupational therapy, individual and group therapy. RESULTS: The outcome of the rehabilitation program in this patient was significantly better than expected. DISCUSSION AND CONCLUSION: This case report shows that being the center of the rehabilitation team the patient takes an active part in setting objectives of the rehabilitation program, whereas involvement of the family, knowledge on necessary medical issues about the disease, contribute to better motivation and better outcome of the rehabilitation program in patients with hemiplegia caused by cerebrovascular insult. PMID- 11214488 TI - [Simultaneous extracranial and intracranial otogenic complications]. AB - INTRODUCTION: Chronic otitis media is the most common cause of otologic complications. A simultaneous occurrence of extracranial and intracranial otologic complications is rare in clinical practice. In this paper, we are presenting a patient with exacerbation of chronic otitis media and associated otologic complications: peripheral facial nerve palsy and subdural cerebral abscess. CASE REPORT: A patient aged 56 who has suffered from chronic otitis media during the past 37 years, was admitted at the Clinic of Otorhinolaryngology due to worsening of the underlying disease. The clinical examination revealed chronic otitis media with granulation in the external auditory canal, pulsatile discharge and extracranial otologic complication--facial nerve paralysis. The preoperative diagnostic procedure included: cochleovestibular investigations (hearing disorder of mixed type on the left side with normal labyrinthine function), temporal bone radiography (sclerotic cell alteration of mastoid on the left), topodiagnosis of facial nerve). The laboratory finding confirmed increased number of leukocytes (21.7 x 10(9)/l), increased erythrocyte sedimentation rate (25/58 mm/h), increased fibrinogen (5.0 g/l) and presence of protein in urine. Chest and heart X-ray findings were normal. Staphylococcus aureus was isolated from ear discharge by microbiological investigation. Signs of meningitis were negative, the liquor was colorless, slightly stirred up with total number of cells 384 x 10(6)/l, sugar 2.7 mmol/l and total proteins from 0.82 g/l. Bacteriological liquor culture was negative. The ophthalmologic examination confirmed normal finding of the eye fundus and absence of increased cranial pressure. For further diagnostics CT (computerized tomography) and MRI of head (magnetic resonance imaging) were performed. The findings confirmed subdural abscess and suspected encephalitic foci of the left cerebral lobe. According to findings, surgery involving radical trepanation of the temporal bone, decompression of facial nerve, denudation of sigmoid sinus dural sinus and angle area and incision of dura mater of the cranial fossa posterior with drainage of subdural abscess (meningitis surgery) was performed. CONCLUSION: A simultaneous occurrence of extracranial and intracranial otologic complications accompanied by subdural abscess is rare in clinical practice. The mechanism of development and spreading of subdural abscess is very interesting. In this case, subdural abscess caused the reaction of dura mater, which has prevented spreading of the disease by cerebrospinal liquid at the onset. However, there is a possibility of its further spreading by blood vessels into the brain white substance, where encephalitic foci may develop and later brain tissue abscesses as well. The clinical course of subdural abscess may be atypical, without headache and increased cranial pressure. This kind of disease demands a complex diagnostic procedure, sufficient otosurgical and neurosurgical interventions, cooperation with infectologist and administration of antibiotic therapy. PMID- 11214489 TI - Smallpox vaccination in Senta County in the early 19th century. AB - The objective of this paper was to report data on vaccination against smallpox in the first decades of the 19th century in the documentation of the historical archives of Senta. The most important documents regulating smallpox vaccination, its control and way of conducting it are presented in complete. One of the most important documents is a poster proclamation from 1814 by which vaccination of children against smallpox was requested. Another document from 1817 was found and it certifies, with great certainty that at that time (or since that time) vaccination against smallpox was present at the territory of Senta. Authors consider that these documents are of utmost importance and that they represent documents enriching history of medicine in our regions. PMID- 11214490 TI - [News in oral therapy of diabetes mellitus]. AB - INTRODUCTION: Recent interest in regard to therapy of diabetes mellitus has focused on novelties in the field of insulin and other kinds of therapies disregarding the contemporary achievements in oral therapy. DIETARY PLANT FIBER: Dietary habits and food preferences in developed countries reveal lack of dietary plant fiber associated with the epidemiologic expansion of widespread noninfectious diseases (metabolic, cardiovascular and some malignant neoplasms). INHIBITORS OF INTESTINAL ALPHA-GLYCOSIDASES: These are substances which competatively and reversibly inhibit the intestinal alpha-glycosidases. The best known among them is acarbose, already in clinical usage for some time. Its wide application has been limited due to fairly distressing side effects. NEW ORAL HYPOGLYCEMIC AGENTS: Although metformin is not a new agent, it deserves attention because it is a novelty in our country. It is extremely useful in therapy of obese diabetics with insulin resistance and hyperinsulinemia. Furthermore, glimepiride--a new sulphonyluretic agent is also at disposal, being better than the previous due to not inhibiting vasodilatory reaction and so it can be used in treatment of some heart diseases. A completely new group of oral hypoglycemics is represented by thiazolidine agents which represent the so-called insulin sensitisers. Apart from that, they have a favourable effect on some lipid fractions and arterial blood pressure. SOME OTHER HYPOGLYCEMIC AGENTS: Among numerous substances with hypoglycemic effect it seems that in the future sulphonyluretic agents might be replaced by benzoic acid preparations. PMID- 11214491 TI - Superstition vs science. More sinned against than sinning. PMID- 11214492 TI - The origins and nature of the cognitive paradigm: an overview. AB - Although cognitive science, the 'science of mind' is generally regarded as of relatively recent vintage, its origins can actually be traced back to ideas from the 1930s. The purpose of this paper is to offer a view of the essential nature of what has come to be called the cognitive paradigm--the framework around which cognitive science has come to be constructed--and about its origins and development. Of particular note is the interdisciplinarity of the field, with its strong links to psychology, linguistics, neurobiology, computer science and philosophy. As will be explained below, this interdisciplinary character is rooted in the historical development of the science itself, and can only be understood in such a context. Thus, the present article is strongly historical in spirit and content. PMID- 11214493 TI - Cardiovascular responses to head-down-body-up postural exercise (Sarvangasana). AB - Sarvangasana (SVGN) is a head-down-body-up postural exercise in a 'negative g' condition. Though highly recommended as one of the three best of all the asanas it has not yet been studied for its very obvious effects on the cardiovascular (CV) functions. This paper reports the results of the first systematic investigation on SVGN employing echocardiographic analysis in eight healthy male subjects before and after a practice of this asana twice daily for two weeks. The resting heart rate (HR) and left ventricular end-diastolic volume (LVEDV) were significantly reduced (P < 0.02, P < 0.01 respectively) after practising this asana. A tendency toward a mild regression of the left ventricular mass was noticed, though it was not statistically significant. The CV responses to acute 45 degrees head-down tilt (HDT) in a tilt table was not altered after practising this asana. Also there was no orthostatic intolerance during the 3-5 min period of 70 degrees head-up tilt (HUT). These results strongly indicate that further studies of this asana performed for a longer period is most likely to yield very significant observations of applied value. PMID- 11214494 TI - Effects of exogenous vitamin C on ethanol toxicity in rats. AB - The effect of a mega dose of ascorbic acid (200 mg/100 g body wt.) on alcohol induced toxicity in rats was evaluated. In rats administered alcohol and ascorbic acid, malondialdehyde (MDA), hydroperoxide and conjugated dienes decreased in comparison with that given alcohol alone. The reduced activities of scavenging enzymes, e.g. superoxide dismutase (SOD) and catalase, in ethanol-administered rats were also enhanced by the co-administration of ascorbic acid and ethanol. Co administration of ethanol and ascorbic acid reduced phospholipids and MDA levels of the erythrocyte membrane in comparison with that of the ethanol fed rats. The reduction in the activities of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), gamaglutamyl transpeptidase (GGT) and the decrease in triglycerides levels also clearly showed the protective action of ascorbic acid in reducing ethanol induced toxicity. PMID- 11214495 TI - Comparative profiles of sodium valproate and ethosuximide on electro-behavioural correlates in gamma-hydroxybutyrate and pentylenetetrazol induced absence seizures in rats. AB - Sodium valproate (VPA) and ethosuximide (ESM) were compared on behavioural and EEG changes in gamma-hydroxybutyrate (GHB) and pentylenetetrazole (PTZ) rat models of Absence Seizures (AS). Both GHB, 100 mg/kg i.p. and PTZ, 20 mg/kg i.p., produced repetitive episodes of staring and immobility with concomitant 6 to 9 Hz spike and wave discharges (SWDs) in the EEG. The parameters used for drug evaluation were the number and duration of SWDs/hour. Though the number of SWDs/hour produced by GHB and PTZ were not significantly different, the duration of SWDs was significantly longer in GHB treated rats (P < 0.001) VPA and ESM, at 200 mg/kg i.p., reduced SWD number and duration in GHB pretreated rats, whereas ESM, 50 mg/kg i.p., was four times more effective than VPA, 200 mg/kg i.p., in the PTZ model. Phenytoin (PHY) 20 and Carbamazepine (CBZ) 10 mg/kg i.p., worsened AS, a feature which has also been reported clinically. Both rat models of experimental AS can be used to defect potential anti-absence activity in new chemical entities. PMID- 11214496 TI - Lipid peroxidation and antioxidant enzyme levels of intestinal renal and muscle tissues after a 60 minutes exercise in trained mice. AB - To investigate the effect of blood perfusion difference on oxidant status, mice were trained by a 7-week running program. Two days after the last training session, mice were exercised for 60 minutes at the same training intensity. Changes in the concentration of thiobarbituric acid reactive substance (TBARS), as an index of lipid peroxidation, in intestine, kidney and muscle, were studied in trained mice immediately (0 h), 3 h and 24 h after the running exercise and in unexercised control group. The activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and xanthine oxidase (XO) were determined in these tissues. Tissue SOD activities were unaffected by the exercise. Muscle GPx activity increased after exercise (0 h and 3 h group, P < 0.01) and returned to control levels at 24 h, but there was not any significant difference in intestinal and renal tissues. Renal tissue XO activity could not be determined. There was not any significant difference among groups in intestinal tissue XO activity. The activity of XO was decreased only in skeletal muscle at 0 h (P < 0.05). TBARS levels of exercised groups were higher than control in muscle (P < 0.01). Intestinal TBARS levels decreased at 0 h (P < 0.05), than reached to control level. Renal TBARS levels of 0 h and 24 h group was higher than control (P < 0.01, P < 0.01 respectively). The results show that a long distance running exercise may cause lipid peroxidation damage in skeletal muscle and kidney. PMID- 11214497 TI - The effect of delta sleep-inducing peptide on the EEG and power spectra in rat. AB - The effects of delta sleep-inducing peptide (DSIP) on the EEG and power spectra of adult male Wistar rats (b.w. 180-220 g) were studied by power spectra analyses of EEG wave forms recorded continuously for 12 h after DSIP administration. The animals were given DSIP i.p. (1 mg/kg). Saline-injected rats served as the corresponding control. Recorded bursts of high amplitude EEG in the 1-9 Hz range (delta and theta) were found to be more frequent in DSIP-treated animals, while power spectra and (delta) wave activity were enhanced in comparison with the control and a statistically significant increase was registered in all experimental points after DSIP (2 h P < 0.05; 4 h P < 0.05; 5 h P < 0.05; 6 h P < 0.05; 7 h P < 0.01; 11 h P < 0.05). In addition, DSIP significantly elevated both the EEG output in the (delta) range and sleep activity. These results suggest that DSIP should be considered as a potential agent for the treatment of sleep disturbances in human medicine. PMID- 11214498 TI - Experimental evaluation of Bocopa monniera on rat gastric ulceration and secretion. AB - The anti-ulcerogenic effect of fresh juice from the whole plant of Bocapa monniera Wettst. (BMJ) commonly known as Brahmi in Hindi was examined using gastric ulcer models induced by ethanol, aspirin, 2 h cold restraint stress and 4 h pylorus ligation. Bocapa monniera juice (BMJ) at doses of 100 and 300 mg/kg and sucralfate at a dose of 250 mg/kg were given orally, twice daily for 5 days. BMJ 100-300 mg/kg produced significant antiulcer activity in all the experimental gastric ulcer models except in case of ethanol-induced ulcers where 100 mg/kg was not found to decrease it significantly. BMJ (100-300 mg/kg) was found to have little or no effect on the offensive acid-pepsin secretion, while cell shedding (microgram DNA/mg of protein) and mucin secretion in terms of total carbohydrates:protein ration (TC:P), the two important parameters of defensive factors were significantly decreased and increased respectively indicating enhancement of protective mucosal factors. Both BMJ (300 mg/kg) and SF showed tendency to increase the mucosal glycoproteins in terms of TC:P, though individual carbohydrates and total carbohydrates were either increased or showed a tendency to increase. Thus, ulcer protective effect of BMJ may be due to its effect on mucosal defensive factors like enhanced mucin secretion, mucosal glycoprotein and decreased cell shedding rather than on offensive factors such as acid and pepsin. PMID- 11214499 TI - Status of pulmonary function tests in adolescent females of Delhi. AB - Progesterone is known to cause hyperventilation and hypercapnia in the luteal phase of a normal menstrual cycle. Viewing this fact lung functions were measured in 71 girls with a mean age of 14.5 years during their follicular and luteal phase of menstrual cycle. Subjects were grouped into I, II and III depending on the age range. Respiratory functions comprising of FVC, FIVC, TLC, RV/TLC, FEV1, FEV1/FVC, FRC, PEFR, FEF 25%, FEF 50%, FEF 75%, PIFR, RAW and KST respectively were performed using Spiro 232 of PK Morgan under standardized laboratory settings. The anthropometric parameters such as height, weight and arm span were also recorded. The majority of pulmonary functions reflect better values in luteal phase as compared with follicular phase however, a statistically significant higher results of FVC, FIVC, FEV1, and TLC were noticed in group I and group III. These observations suggest a possible role in increased level of progesterone in luteal phase on respiratory system. PMID- 11214500 TI - Effect of nimodipine on male reproductive functions in rats. AB - Nimodipine, a dihydropyridine calcium channel blocker, was administered orally using two different doses (40 mg and 60 mg/kg/day) to rats. Both short term (2 weeks) and long term (6 weeks) effects of the drug were observed. The drug administration resulted in a marked decrease in sperm density, sperm motility and acrozomal reaction. Zona-pellucida penetration by the sperm obtained from drug treated animals was significantly lower when compared with sperm from normal animals. Nimodipine stimulated Ca2+ ATPase activity in isolated plasma membrane of rate spermatozoa. In conclusion, short term and long term administration of nimodipine has deleterious effect on male reproductive functions in rats. PMID- 11214501 TI - Relationship of seminal plasma transferrin with seminal parameters in male infertility. AB - This study was undertaken to investigate whether there is relationship between seminal plasma transferrin and seminal parameters which included sperm count, motility and morphology. The study included 100 male subjects in the age group of 23-41 yrs including 7 proven fertility, 6 post-vasectomised and 87 subjects were of idiopathic infertility. Estimation of seminal plasma transferrin concentration was done by using Mancini's single radial immunodiffusion technique. Study of the seminal parameters (Sperm count, Motility and Morphology) was done by using guidelines of WHO Manual. Mean seminal plasma transferrin concentration in proven fertility subject was 5.35 mg/dl (+/- 2.07) and in normozoospermic subject was 4.63 mg/dl (+/- 2.50) which was significantly higher (P < 0.001) than those of oligozoospermic, azoospermic and post-vasectomised subjects. Coefficient of correlation between seminal plasma transferrin concentration and sperm count was statistically significant (r = 0.3087, P < 0.001). The seminal plasma transferrin concentration was correlated with the percentage of motile sperms and was statistically significant. However no correlation could be demonstrated with various grades of motility. Statistically significant correlation was not found between transferrin and sperm morphology. The present study demonstrates that seminal plasma transferrin concentration is correlated with sperm count and percent motile sperms. Thus sertoli cell secretion-transferin has a positive influence over spermatogenesis and can be used as a marker of testicular function. PMID- 11214502 TI - Event related evoked potential responses in epileptic patients. AB - The effect of epilepsy on cognitive functions has been investigated in this study. The P300 auditory event related potentials (AERP), Wechsler Adult Performance Intelligence Scale (WAPIS--Indian Adaptation) & Digit Span Test (DST) have been used to assess the cognitive status. Twenty primary generalised epilepsy patients and 20 normal controls were subjected to WAPIS & DST testing and their AERP recorded. On comparative statistical analysis, epileptic subjects were found to have significantly higher N2 & P300 latencies and lower P300 amplitude, WAPIS-IQ scores & DST scores. These findings suggest that there is a general decline of cognitive functions in epileptics especially the memory, attention, concentration and speed of mental processing and as also corroborated by P300 and that P300 can be used as an additional sensitive parameter to assess the cognitive status. PMID- 11214503 TI - Effect of head-up tilt on cardiovascular responses in normal young volunteers. AB - Since the cardiovascular effects of tilting are influenced by degree as well as duration of the tilt, we planned to study the time course of blood pressure and heart rate (HR) responses during 30 degrees, 60 degrees, 80 degrees head up tilt (HUT). The study was conducted on 20 volunteers aged 18-20 y who were tilted on a tilting table. Blood pressure was determined by sphygmomanometer and HR was calculated from R-R interval of ECG. 30 degrees HUT produced an insignificant decrease in systolic pressure (SP) and pulse pressure (PP) while diastolic pressure (DP), mean pressure (MP) and rate-pressure-product (RPP) registered an insignificant rise. The changes produced by 60 degrees and 80 degrees HUT were more marked than those produced by 30 degrees HUT. While SP and PP decreased significantly, HR and RPP increased significantly. In conclusion, 30 degrees HUT produces insignificant changes while 60 degrees and 80 degrees HUT produce significant changes in SP, PP and RPP. PMID- 11214504 TI - Long-term effects of postnatal aluminium exposure on acetylcholinesterase activity and biogenic amine neurotransmitters in rat brain. AB - The long-term effects of early postnatal exposure to aluminium on acetyl choline esterase (AChE) activity and on biogenic amines were studied in different brain regions. The subjects were eight days old male Wistar rat pups. They were grouped into normal control and aluminium exposed groups. For aluminium exposure, the pups were gastric intubated with aluminium chloride (40 mg/Kg body weight) for two weeks. Control rats were given equal volumes of distilled water. After the treatment, they were rehabilitated for forty days. On the sixtieth day, the rats from both the groups were sacrificed and AChE activity, levels of dopamine, noradrenaline and serotonin were estimated in the cerebral cortex, hippocampus, septum, brainstem and striatum. In the aluminium exposed group: the AChE activity was significantly decreased in the hippocampus, septum, striatum and brainstem; serotonin levels were reduced by 20% in the cortex, hippocampus, septum and striatum; in brain stem, the serotonin level was decreased by 40%. A 60% reduction in noradrenaline levels was observed in the striatum whereas it was reduced by 25% in other regions except in hippocampus. Though dopamine levels were not altered in the cortex, septum and brainstem, they were reduced by 40% in the striatum. The study documents the long-term consequences of exposure to aluminium during the developmental periods. PMID- 11214505 TI - Minimum muscular fitness in school children. AB - Two hundred and fifty school boys from Lonavla were randomly selected and tested with Kraus-Weber tests for their minimum muscular fitness. The results revealed that 20.8 per cent boys failed in the tests. Multiple failures were 4.8 percent while flexibility failures alone were 11.6 percent. Boys at the age of 15 years failed more in flexibility test. Boys at the age of 10 years had the maximum percentage of failures to the extent of 38.5. Inclusion of Yogasanas in the programme of physical activities of the school is suggested for the improvement of the status of the failures. PMID- 11214506 TI - Changes in fibrinolytic activity of blood after prostatectomy. AB - After prostatectomy, hypofibrinogenemia and bleeding were reported earlier. The objective of present study is to find out, of blood, after prostatectomy. Blood samples of patients posted for operations were studied by following tests before and after operation along with controls. 1. Euglobulin lysis time. 2. Plasminogen assay. 3. Fibrinogen estimation. The results showed clearly that there is decrease in euglobulin lysis time indicating increased plasminogen activator level, increased plasminogen level and decreased fibrinogen level after the operation. This suggests that there is significant increase in fibrinolytic activity of blood after prostatectomy leading to hypofibrinogenemia and clotting defects. PMID- 11214507 TI - Some biochemical changes in heme synthesis in iron deficiency. AB - Some enzymes and intermediates of heme synthesis were determined in blood and urine of 26 women with severe iron deficiency anemia (IDA). Erythrocyte free protoporphyrin was almost doubled and delta-aminolevulinate dehydrase significantly raised. But urinary excretion of delta-aminolevulinic acid and reticulocyte ferrochelatase were significantly reduced in iron deficiency anemia. Hence these could serve as useful indices of iron deficiency and consequent anemia. PMID- 11214508 TI - Effect of alcohol dependence on the levels of duodenal disaccharidases in human subjects. AB - BACKGROUND: The aim of the study was to detect the duodenal enzyme activity in patients of alcohol dependence and to compare with non-alcoholic patients of non ulcer dyspepsia. METHODS: Disaccharidases (lactase, sucrase, maltase) were estimated in 20 non alcoholic patients of non-ulcer dyspepsia and 20 alcoholics admitted to the drug de-addiction and treatment centre of PGIMER, Chandigarh, India. RESULTS: No significant influence of alcohol on enzyme levels in patients of alcohol dependence when compared to patients of non-ulcer dyspepsia was observed. However, a significant decrease in lactase level was noted in patients consuming more than 125 gm/day of alcohol. CONCLUSION: Amount of consumption of alcohol showed decrease in lactase enzyme, but not in maltase and sucrase. There was no effect of duration of alcohol consumption on dissacharidases in the two groups. PMID- 11214509 TI - Increase in circulating products of lipid peroxidation (malonaldehyed) in streptozocin induced diabetic mice. PMID- 11214510 TI - Unipolar depression and serum electrolytes. PMID- 11214511 TI - Effect of examination stress on some metabolic parameters. PMID- 11214512 TI - Antidepressant activity of some phenylaceticacid hydrazones and 2-chlorophenyl semicarbazones. PMID- 11214513 TI - PEFR in relation to phases of pregnancy. PMID- 11214514 TI - Infertility and psychosexual disorders: relationship in infertile couples. AB - 175 consecutive infertile couples were interviewed together and individually in accordance with a 25 point questionnaire. Amongst the males, premature ejaculations 66% was most common problem followed by erectile dysfunction 15%, decreased libido 11% and orgasmic failure 8%. Amongst females dyspareunia 58%, decreased libido 28% and orgasmic failure 14% were most common problems. Various type of misconceptions were also observed in the infertile couples. Lack of sexual awareness and education formed an important part of observations. Psychosexual dysfunction and infertility was found to occur, in a large number of couples, together in association. Most common cause for this problem seems to be ignorance and lack of sex education. PMID- 11214515 TI - Foreign body in injury--an important evidence. AB - In the present paper, a complete case is discussed, that is from the crime upto judgement in the court of law, from the Forensic point of view. The postmortem examination was conducted by the author in which a metallic fragment of size of a mustard seed was found in a incised wound. On chemical analyzers examination, the metal fragment matched with the suspected weapon, in respect of spectrochemical contents. This evidence became an important part in the investigation for conviction of the accused in the court of law. This indicates that when-ever any foreign body, whatever it may be or of whatever size, should not be neglected while examining the injury before death of after death, since it can become an important piece of evidence. PMID- 11214516 TI - Transient asceptic arthritis of knees in a patient with melioidosis. AB - Osteomyelitis and septic arthritis are known manifestations of melioidosis. Whether reactive arthritis can occur as a sequele to B. pseudomallei infection, is yet to be seen. As more and more cases of melioidosis will be reported in future, this aspect has to be kept in mind. PMID- 11214517 TI - Levels of lactic acid, normal level & its relation to food, glucose, cholesterol, raised blood urea and phenformin therapy. AB - 1. The level of lactic acid was found to be 25 mg percent in 95 percent of 186 normal Indians. There was no difference due to sex and age. 2. Level of lactic acid was estimated in blood of normal persons and diabetics Type II patients to observe the effects of food and glucose. There was no change except the level of lactic acid was in higher but in normal range. 3. Hyperglycemia of over 300 mg raised the blood lactic acid in 25 percent of patients. 4. Lactic acid was not affected by hypercholesteremia but was raised in 60 percent of cases with raised blood urea. 5. Lactic acid was found to remain within normal limits in 48 type II diabetics treated with phenformin dose varying from 50 mg to 225 mg per day. The duration of treatment varied from one year to seven years. PMID- 11214518 TI - Memory 'photographed' for the first time. PMID- 11214519 TI - Leprosy elimination moves a step nearer. PMID- 11214521 TI - Hyperkalemia. PMID- 11214520 TI - Adolescent's sexual and reproductive health, behavioural change and the application of psychosocial theories. PMID- 11214522 TI - EMS under the new Medicare fee schedule. PMID- 11214523 TI - Enhancing patient care during interhospital transport. PMID- 11214524 TI - A is for airway: needle techniques to the neck. AB - The purpose of this article is only to introduce these procedures. More extensive review of the procedures and instruction by a qualified professional are mandatory before proceeding further. The three procedures are very similar, using the same anatomic location and many of the same techniques. They allow you to establish a secure airway rapidly; however, the skills needed to do them must be practiced on a regular basis and performed by people who are familiar with ACLS procedures, are intimately aware of airway anatomy and are skilled at doing endotracheal intubation. Since these techniques are probably used infrequently, a regular training schedule should be established, along with competency testing. Whichever procedure is used will enable appropriately trained and competent personnel to get a patient through a life-threatening situation quickly. PMID- 11214525 TI - EMS for the masses. Preplanning your EMS response to a major event. PMID- 11214526 TI - When leaders lead ... employees commit. PMID- 11214527 TI - Making the money match. PMID- 11214528 TI - 21st century EMS: are you ready for the challenge? PMID- 11214529 TI - Disease transmission by mouth-to-mouth resuscitation. PMID- 11214530 TI - Stats & facts. Growth of ambulatory surgery centers continues. PMID- 11214531 TI - Thinking through e-health care return on investment. PMID- 11214532 TI - Revisiting the "ideal" health care system: what happened to the Rochester model? PMID- 11214533 TI - Health care resource evaluation. PMID- 11214534 TI - Selection criteria and external validity. PMID- 11214535 TI - In search of ... connectivity. PMID- 11214536 TI - The management of hypercholesterolemia revisited. AB - Coronary artery disease (CAD) is the major cause of death in the United States. This disease places a large economic burden on society stemming from both loss of productivity and use of health care resources. The primary factor that has been extensively correlated with risk for CAD is elevated cholesterol levels. The lack of efficacy with dietary restriction alone and the limitations, adverse effects, and drug interactions associated with current lipid-lowering therapies have caused health care providers to search for safer and more efficacious agents. PMID- 11214537 TI - Effect of sumatriptan on health care resource use among patients with migraine. AB - Previous investigations examining health care resource utilization in patient populations have shown patients with migraine to consume significantly higher health care resources compared with individuals without migraine. The purpose of this study was to compare health care resource and narcotic use in migraineurs prescribed sumatriptan (oral, subcutaneous, or nasal) with those not prescribed sumatriptan. PMID- 11214538 TI - The board's role in diagnosing organizational performance. PMID- 11214539 TI - Being a good environmental neighbor. PMID- 11214540 TI - Executive coaching: a new demand. PMID- 11214541 TI - Benchmarking in HR: ask the right questions. PMID- 11214542 TI - From the assembly line to the emergency room: GM enhances quality improvement in the health care industry. PMID- 11214543 TI - The lean team. PMID- 11214544 TI - Two become one through collaboration. PMID- 11214545 TI - Contract management: management's tool for better operating results. PMID- 11214546 TI - Medical malpractice coverage: a look back and a look forward. PMID- 11214547 TI - We cannot get there from here. PMID- 11214549 TI - Michigan hospitals exceedingly efficient. PMID- 11214548 TI - Sustaining our calling and cause. PMID- 11214551 TI - Revisions to Medicare coverage appeals procedures issued. PMID- 11214550 TI - Optimizing performance is no longer an option. PMID- 11214552 TI - Getting the most from receivable-support vendor agreements. PMID- 11214553 TI - [Teleradiology. The experience in Panama]. AB - The technological advances have brought today procedures, that were not possible a few years ago. Telemedicine is one of them. Teleradiology in particular is one of the specialty where this application has been more important. PMID- 11214554 TI - [Myasthenia gravis in Santo Tomas Hospital 1990-1997]. AB - Myasthenia Gravis is an infrequent disease. Diagnosis and treatment must be done early to avoid high morbidity that can compromise patients lives. Nine cases were identified during the eight year 1990-1997 at the Santo Tomas Hospital of Panama city but one had to be excluded because he refused treatment. Most of the patients (7/8) had symptoms for more than 3 months. The diagnosis of Myasthenia Gravis requires a high index of suspicion and the clinical impression must be confirmed by various diagnostic studies that include the edrophonium test, the repetitive stimulation test, the therapeutic test with pyridostigmine, the determination of acetylcholine anti-receptor antibodies and a CT Scan of the thorax. Medical treatment consists mainly of anticholinesterase agents and surgical treatment consists of thymectomy by means of an extended transternal ablation. Operative results were excellent, seven out of eight improved. PMID- 11214555 TI - [Psychosomatic medicine and gastroenterology]. AB - The possible relationship between psychosomatic medicine and gastroenterology is described and more specifically in the question of peptic ulcer which gave rise to the psychosomatic theory, prevalent in 1950-85. The infectious theory (H. pylori), that arose within the last decade, was discussed and the question was posed in the direction that one theory was not exclusive of the other but in fact were probably complementary of each other. PMID- 11214556 TI - [Correlation between myocardial perfusion and coronary angiography]. AB - Determining the severity of coronary heart disease is of great importance to the cardiologist. There is a very good correlation between the severity of coronary heart disease and perfusion abnormalities to the myocardium as determined by radioisotope studies. We present our experience with forty (40) cases of ischemic heart disease diagnosed with sestamibi and its correlation with the obstruction of the coronary arteries by angiography. There is good correlation between the sestamibi findings and the coronary artery angiography obstructions and our findings concur with those published in the literature, which is between 75-85%. PMID- 11214557 TI - [Importance of Mycoplasma pneumoniae and Chlamydia pneumoniae in children with community-acquired pneumonia]. AB - OBJECTIVES: To determine the importance of Mycoplasma pneumoniae and Chlamydia pneumoniae in community-acquired pneumonia (CAP) of children from different latitudes and to compare clinical outcome using azithromycin (AZM) versus either amoxicillin-clavulanate (A-C) or erythromycin estolate (EE). METHODS: Ambulatory patients with CAP were identified at either the Children's Medical Center of Dallas, Texas or the Hospital del Nino of Panama City, Panama. Children 6 months to 15 years of age were enrolled and randomized to receive either AZM for 5 days or a 10 day course of either A-C or EE, for those younger or older than 5 years of age, respectively. Mycoplasma pneumoniae and C. pneumoniae were identified by measuring acute and convalescent serum antibody titers and by performing nasopharyngeal (NP) and oropharyngeal (OP) swabs for culture and polymerase chain reaction (PCR) testing. RESULTS: Overall 335 patients (168 in Dallas and 167 in Panama) were evaluated from February 1996 through December 1997. Acute M. pneumoniae infection was detected in 12 (7%) patients each in Dallas and Panama. Acute C. pneumoniae infection was observed in 10 (6%) children at each site. Infection caused by these "atypical" microorganisms occurred more frequently in children older than 5 years of age (23% vs 9%, P = 0.001, RR 2.5, 95% CI 1.4 4.3). No distinctive pattern of clinical or radiologic abnormalities was seen in relation to etiology. Clinical cure was achieved in 43 of 44 children infected by these bacteria regardless of treatment assignment. CONCLUSION: Mycoplasma pneumoniae and C. pneumoniae are common etiologic agents of CAP in older children from different latitudes. Children with CAP present with similar clinical and radiologic findings to those caused by other etiologic agents. Outcome was excellent for the three treatment regimens studied. PMID- 11214558 TI - [Comparative study in postmenopausal women with osteoporosis (sodium alendronate, calcium and HRT vs sodium alendronate and calcium]. AB - In 1995 Alendronate was approved by the FDA for the treatment of Post-Menopause Osteoporosis. Their use for the preventive treatment on Osteopenic patients is approved in 1996. Calcium is a very important element in the treatment of Osteoporosis, because it is the only one that acts in the mineralization phase. It is well known that the first line to stop the loss of DMO in Post-Menopausic women are Estrogens. If we add TRH to the therapy, the effects of Alendronate will raise significantly. The first group (A) of 32 patients received Alendronate, Calcium and TRH. In the second group (B), there were 35 patients and they received Alendronate and Calcium. The groups were statistically compared and selected. In both groups the lumbar column was more affected than the hips. The use of TRH associated with Alendronate for the lumbar column significantly raised the percentage of change of DMO in 24 months. The change percentage was of 9% of DMO for group A and 5.25% for group B, giving a significant difference of 3.75% of DMO. For the hips the use of TRH associated with Alendronate did not have any difference in raise between both groups. In the next twelve months there was a change of 3.2% of DMO more in group A than in group B. In 24 months the change of DMO in the hips was of 7.95% in group A and 4.75% for group B. The TRH decrease the vasomotor symptoms, and improves the hormonal levels (FSH and Estradiol) keeping their benefits effective (Cardioprotectors, Neuroprotectors, etc.) but it potentiates the decrease of the bone reabsorption shown by the Alendronate. This significantly increases the change of percentage of DMO, obtaining densiometrics and clinical improvements in less time than using only Alendronate and Calcium. Also decreases the price of the treatment and the risk of fracture in less time, offering in that way a better quality of life to our patients. PMID- 11214559 TI - [Cardiac insufficiency and B-blockers]. AB - This article summarise our experience with the Beta-Blocker in the management of congestive heart failure, which did not respond to the usual medical treatment. PMID- 11214560 TI - EBRI research highlights: retirement and health data. PMID- 11214561 TI - [Sensitivity and specificity of physical examination]. PMID- 11214562 TI - [The circulatory system]. PMID- 11214563 TI - [The cranial nerve system]. PMID- 11214564 TI - [The digestive system]. PMID- 11214565 TI - [The respiratory system]. PMID- 11214566 TI - [The endocrine system]. PMID- 11214567 TI - [Collagen diseases]. PMID- 11214568 TI - [Infections]. PMID- 11214569 TI - [Kidney and urologic system]. PMID- 11214570 TI - [Breast and lymph nodes]. PMID- 11214571 TI - [Fundus oculi]. PMID- 11214572 TI - [Examination of patients in coma]. PMID- 11214573 TI - [Needs and importance of physical examination: discussion]. PMID- 11214574 TI - [Secondary amyloidosis and crescentic glomerulonephritis in a patient with rheumatoid arthritis]. PMID- 11214575 TI - [Familial tumor forming chronic pancreatitis of juvenile onset]. PMID- 11214576 TI - [Protein-losing gastroenteropathy effectively treated by prednisolone]. PMID- 11214577 TI - [Type I homocystinuria associated with megaloblastic anemia]. PMID- 11214578 TI - [An autopsy case of polyarteritis nodosa with myeloperoxydase-antineutrophil cytoplasmic antibody (P-ANCA) and clinical features of microscopic polyangiitis]. PMID- 11214579 TI - [Current status of the treatment of Alzheimer's disease]. PMID- 11214580 TI - [The forefront of arrhythmia therapy: progress in the management of atrial fibrillation]. PMID- 11214582 TI - The Parasitological Society of Southern Africa 26th Annual Scientific Meeting. 9 11 September 1998. Mont-aux-Sources, South Africa. Abstracts. PMID- 11214581 TI - [Muscular dystrophy: recent progress]. PMID- 11214583 TI - Selected topics from Food Micro '99. 17th International Conference of the International Committee on Food Microbiology and Hygiene. September 13-17, 1999. Veldhoven, The Netherlands. PMID- 11214584 TI - Proceedings of the 2nd International Symposium on the Developmental Aspects of Androgen Excess Disorders. Toronto, Canada, June 20, 2000. PMID- 11214585 TI - Professor Andre Delmas. PMID- 11214586 TI - B1 Lymphocytes in B Cell Neoplasia. Proceedings of the 16th Workshop on the Mechanisms of B Cell Neoplasia. Bethesda, Maryland, USA. October 28-29, 1999. PMID- 11214587 TI - Brain Energy Metabolism: Relationship to Development and Disease. Proceedings of the 4th International Conference on Brain Energy Metabolism. Oxford, United Kingdom, August 14-18, 1999. PMID- 11214588 TI - Peritoneal dialysis catheter infections and peritonitis in children: a report of the North American Pediatric Renal Transplant Cooperative Study. AB - Peritonitis and catheter-related infections remain the two most-common causes of peritoneal dialysis (PD) treatment failure. To define the frequency and risks associated with exit site/tunnel infections (ESI/TI), as well as peritonitis, in pediatric patients on PD, we undertook a retrospective cohort study of patients initiated on PD in the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). We examined demographic data and PD catheter characteristics of 1,258 patients, aged < or = 21 years, initiated on PD from 1992 to 1997. We examined the frequency and complications of ESI/TI occurring within 30 days, 6 months, and 1 year of follow-up. For peritonitis episodes, we examined patient risk factors for peritonitis. Almost 11% of patients had an ESI/TI at 30 days, 26% between 30 days and 6 months, and 30% between 6 months and 1 year of follow up. There was no increased risk of ESI/TI associated with patient age, race, or catheter characteristics. Peritonitis occurred in dialysis patients at a rate of 1 episode per 13.2 patient months. Proportional hazards regression analysis demonstrated that black race, single-cuffed catheters, and upward pointing exit sites were independent risk factors for peritonitis in the pediatric PD population. Patients with ESI/TI had twice the risk of those without these infections of developing peritonitis or needing access revision, and an almost threefold increased risk of hospitalization for access complications/malfunction. ESI/TI occurs commonly in pediatric PD patients. These infections cause significant morbidity, through risk of peritonitis, access revision, and hospitalization for catheter complications. Further study of potentially modifiable risk factors for ESI/TI in pediatric end-stage renal disease patients is warranted. PMID- 11214589 TI - Apoptosis parallels ceramide content in the developing rat kidney. AB - Ceramide is emerging as an important hydrophobic sphingolipid involved in cell differentiation and apoptosis. Since apoptosis plays a significant role in cellular remodeling during renal morphogenesis, we measured ceramide content and apoptosis in the fetal (18 days gestation), neonatal (3, 7, and 14 days postnatal), and adult rat kidney. In addition, to determine whether developmental changes in ceramide content are tissue-specific, we compared renal ceramide content with that in lung and liver. Ceramide was measured by the diacylglycerol kinase assay, and apoptosis was determined by the TUNEL technique. Renal ceramide content fell over 100-fold from the fetus to the 7th postnatal day. Renal apoptosis paralleled ceramide content, with a greater than 300-fold decrease in apoptosis from fetal to adult life. Ceramide content of the lung and liver was significantly less than that of the kidney, and changed less with maturation. We conclude that maturational changes in ceramide content are tissue-specific, and that the high rate of apoptosis in the developing kidney may be related to the elevated ceramide content. PMID- 11214590 TI - [Proceedings of the Joint Congress of the SIAPEC-IAP. Italian Society of Pathologic Anatomy and Diagnostic Cytology. Bolzano, Italy, 24-27 May 2000. Abstracts]. PMID- 11214591 TI - The Healthy Home Summit: The Significance of Cleanliness and Disinfection in the Home and its Link to Infection Control. Proceedings of a conference. New York, New York, USA. November 6, 1999. PMID- 11214592 TI - Alterations in the proliferative response of peripheral lymphocytes in tick-borne encephalitis. PMID- 11214593 TI - Reversed sequence of repolarization in the rabbit ventricular epicardium under hypothermia. PMID- 11214594 TI - Functional state of the circulatory and external respiratory systems under hyperbaric oxygenation. PMID- 11214595 TI - Growth and survival of cyanobacteria in water from blooming and nonblooming ponds under experimental conditions. PMID- 11214597 TI - Role of the ecdysteroid system in the regulation of Drosophila reproduction under environmental stress. PMID- 11214596 TI - The role of p-aminobenzoic acid in DNA protection against oxidants. PMID- 11214598 TI - Cadaverine as a signal of heat shock in plants. PMID- 11214599 TI - A 55-year-old man with right-sided weakness. PMID- 11214600 TI - Protein kinase C suppresses spontaneous, transient, outwards K+ currents through modulation of the Na/Ca exchanger in guinea-pig gastric myocytes. AB - The effect of protein kinase C (PKC) on the Ca2+-activated K+ current (IK,Ca) in guinea-pig gastric myocytes was studied using the whole-cell voltage-clamp technique. At a holding potential of 0 mV, IK,Ca, recorded as spontaneous, transient, outwards currents (STOCs), was markedly inhibited, both in mean amplitude (54 +/- 5%) and frequency (60 +/- 8%) by 1 microM phorbol 12, 13 dibutyrate (PDBu, n = 6). These effects were antagonized by pretreatment with 10 nM bisindolylmaleimide I (n = 5), a selective inhibitor of PKC. The possibility that the inhibition of STOCs was due to direct channel inhibition by PKC was addressed using inside-out or open-cell-attached patch-clamp techniques, the latter established using beta-escin. PDBu did not alter the conductance or open probability of the KCa channel in any mode, suggesting that PKC does not inhibit the KCa channel directly. To study the involvement of the Na/Ca exchanger in the inhibition of STOCs by PDBu, its operation was prevented by replacing Na+ in the internal solution by tris(hydroxymethyl)aminomethane (TRIS) and external Na+ by equimolar K+ and Ca2+-activated inwards K+ currents recorded at a holding potential of 0 mV. Neither the mean amplitude (96 +/- 8%) nor the frequency of these currents was inhibited significantly by 1 microM PDBu (n = 5). Like PDBu, 5 microM 2-(2-[4-(4-nitrobenzyloxy)phenyl]ethyl) isothiourea methanesulphonate (KB R7943), a selective inhibitor of the reverse mode Na/Ca exchanger, also inhibited the mean amplitude (45 +/- 6%) and frequency (26 +/- 2%) of STOCs at the holding potential of 0 mV (n=6). The results suggest that the suppression of STOCs by PKC is mediated by inhibition of the Na/Ca exchanger. PMID- 11214602 TI - Dr Hanns Pacy. From turmoil to tea gardens. PMID- 11214601 TI - Symptom profiles in children with ADHD: effects of comorbidity and gender. AB - OBJECTIVE: To examine ratings and objective measures of attention deficit/hyperactivity disorder (ADHD) symptoms to assess whether ADHD children with and without comorbid conditions have equally high levels of core symptoms and whether symptom profiles differ as a function of comorbidity and gender. METHOD: Four hundred ninety-eight children from the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA) were divided into comorbid groups based on the parent Diagnostic Interview Schedule for Children and assessed via parents' and teachers' Swanson, Nolan, and Pelham (SNAP) ratings and a continuous performance test (CPT). Comorbidity and gender effects were examined using analyses of covariance controlled for age and site. RESULTS: CPT inattention, impulsivity, and dyscontrol errors were high in all ADHD groups. Children with ADHD + oppositional defiant or conduct disorder were rated as more impulsive than inattentive, while children with ADHD + anxiety disorders (ANX) were relatively more inattentive than impulsive. Girls were less impaired than boys on most ratings and several CPT indices, particularly impulsivity, and girls with ADHD + ANX made fewer CPT impulsivity errors than girls with ADHD-only. CONCLUSIONS: Children with ADHD have high levels of core symptoms as measured by rating scales and CPT, irrespective of comorbidity. However, there are important differences in symptomatology as a function of comorbidity and gender. PMID- 11214603 TI - [Locoregional neuraxial anesthesia and vascular surgery: the benefits]. AB - PURPOSE: To assess the advantages of neuraxial blockade (NB) during and after vascular surgery and to confront them with the risk of epidural or spinal hematoma. MAIN FINDINGS: NB may reduce the risk of thrombotic occlusion following lower extremity vascular reconstruction. This effect of NB may be attributed to reduced hypercoagulability, decreased peripheral resistance and increased graft flow. In patients under general anesthesia, only those authors using an aggressive perioperative management (pulmonary artery catheter monitoring, intensive care unit admission) were able to report grafts patency rates similar to those obtained with NB. NB facilitates the modulation of the hemodynamic and hormonal stress responses during the perioperative period. It also produces superior postoperative analgesia. Still, the impact of NB on cardiac morbidity following aortic reconstructive surgery remains open to debate. Only very few cases of epidural hematomas associated to NB following vascular surgery have been reported. They implicated patients who received either fibrinolytic medication, continuous heparin infusion, or both. Low molecular weight heparins may increase the risk or epidural hematoma and, should their administration become more frequent during vascular surgery, the safety of NB would then have to be reassessed. CONCLUSION: NB during vascular surgery is a safe and well-established practice. It offers many theoretical and demonstrated advantages. NB is particularly beneficial and economical for lower extremity vascular reconstruction. Still, NB may not be the best approach if the administration of fibrinolityc medication or prolonged heparin infusion is contemplated. PMID- 11214604 TI - [Locoregional neuraxial anesthesia as used in vascular surgery]. AB - OBJECTIVES: Neuraxial blockade (spinal or epidural anesthesia) is still widely used in patients undergoing vascular surgery. However, the combined administration of anticoagulants and antiplatelet agents may compromise the safety of this technique with regards to the potential occurrence of a spinal or of an epidural hematoma. We review the benefits and risks of neuraxial blockade in light of the evolution of anticoagulation for vascular surgery. MAIN FINDINGS: Vascular surgery generally requires a high level of intraoperative anticoagulation. An increasing number of patients are also treated pre and post operatively with antiplatelet agents. Their administration cannot be interrupted without serious risks to the patients' cardiovascular system and, further their continued use during surgery may improve graft permeability. Recent reports have emphasized the danger of neuraxial anesthesia in patients receiving low dose anticoagulation. So, high doses of heparins should carry an ever higher risk of serious complications in patients undergoing neuraxial blockade. Furthermore, no published data has ever demonstrated convincingly the benefit of either epidural or spinal anesthesia over general anesthesia. No differences have ever been documented in terms of cardio-vascular morbidity, graft patency, and mortality. CONCLUSION: Routine neuraxial blockade cannot be recommended in patients undergoing vascular surgery. The decision to perform a neuraxial block in such a patient may only be taken on a case by case basis, after careful consideration of expected benefits and potential risks. PMID- 11214605 TI - Global challenges of cervical cancer prevention. PMID- 11214606 TI - Is there a place for molecular biology markers and other prognostic factors in staging gynaecological tumours? PMID- 11214607 TI - The making of a gynecologic oncologist. PMID- 11214608 TI - Evolution in cervical pathology and cytology: a historical perspective. PMID- 11214609 TI - Third generation aromatase inhibitors in metastatic breast cancer patients failing tamoxifen. Randomized comparisons with megestrol acetate: a critical review. PMID- 11214610 TI - Perioperative development of a thrombogenic risk profile in patients with carcinomas of the breast: a cause of increased thrombosis. AB - Within the context of a prospective study we investigated the influence of malignant and benign breast disease on the coagulation systems both prior to and after surgery. In addition we also investigated to what extent individual risk factors aid the formation of a thrombophiliac risk profile. Altogether 50 patients with carcinomas of the breast and 12 patients with benign breast disease were included in the study. The coagulation investigations took place prior to surgery and on the 1st, 3rd, 7th and 10th day following the operation. The results have already revealed that prior to surgery a clear activation of the haemostasis takes place among patients with a carcinoma of the breast. When compared to patients with benign breast conditions there was a far greater plasma level of factor VIII vWF, fibrinogen, thrombin-antithrombin III complex, D-dimer fibrin degradation products, tissue-type plasminogen activator and the activity and the antigen of plasminogen activator inhibitor 1. Also during the postoperative period the malignant tumour was a stimulus for additional increased activity of blood coagulation and fibrinolysis. Individual risk factors such as age, menopausal status, obesity and smoking lead to a thrombogenic risk profile which could provide a possible explanation for the observed increased incidence of thrombosis in breast cancer patients. For the clinical work there is a need for intensive pre- and postoperative monitoring in the cases of patients with malignant tumours including angiological examinations, intensive physiotherapy and a risk-adapted prophylactic anticoagulation. PMID- 11214611 TI - Combined prognostic importance of CA 125, histopathologic grade and DNA-index in advanced ovarian cancer. AB - PURPOSE: To analyse the possible prognostic importance of a combination of serum CA 125 levels, tumor cell DNA distribution and histopathologic grade in patients with epithelial ovarian cancer. METHOD: The study included 41 patients with ovarian cancer stages II-IV. CA 125 was measured before the start of chemotherapy and after every course. The DNA distribution was analysed by flow cytometry in biopsy specimens from the primary tumour. The histopathologic grading was performed according to WHO criteria. RESULTS: The CA 125 level was of major prognostic significance. All patients with an abnormal value (> 35 U/ml) after three courses died within 16 months. The DNA distribution did not add significant prognostic information, but the histopathologic grade was of significant prognostic importance as investigated by Cox analysis. CONCLUSION: CA 125 is an important prognostic marker in epithelial ovarian cancer. The value after three courses of chemotherapy is significant. The histopathologic grade adds further prognostic information. PMID- 11214612 TI - Comparison of endometrial carcinoma coexisting with and without endometrial hyperplasia. AB - OBJECTIVE: It has been reported that endometrial carcinoma has two pathogenic types; one with and the other without endometrial hyperplasia. The present study was done to clarify whether this was true in our series of a large number of Japanese patients. METHODS: Three hundred and twenty-eight patients with endometrial carcinoma were classified into two groups, one coexisting endometrial hyperplasia (group 1; 182 cases) and the other having normal endometrium without endometrial hyperplasia (group 2; 107 cases). The clinical and pathological observations of the two groups were compared. RESULTS: The ages of the patients were significantly lower in group 1 (30-83; mean 50.7) than in group 2 (34-81; mean, 57.2). The incidence of the carcinoma with invasion limited to less than 1/3 of the myometrium, with surgical stage I, lower grade endometrioid type and higher levels of progesterone receptor, and without lymph node metastasis were significantly higher in group 1 than in group 2. The cumulative survival rate for stage I was also significantly higher in group 1 patients. CONCLUSION: A significant difference was found between groups 1 and 2 in age distribution, degree of progress and pathological observations. Stage I patients in the former group had a better prognostic than the latter. PMID- 11214613 TI - Primary carcinoma of the fallopian tube. A report of 19 cases with literature review. AB - Primary carcinoma of the fallopian tube is the rarest cancer of the female genital tract with an incidence of 0.5% of all gynecologic tumors. Since the first report in 1847 about 1,500 cases have been published. Due to similarity of the clinical presentation the staging and therapeutic management have been adapted to that of ovarian cancer. We retrospectively evaluated all the 19 patients who had been diagnosed with primary carcinoma of the fallopian tube at the Department of Obstetrics and Gynecology of the University of Zurich between 1977 and 1998. All lesions were staged according to the rules of FIGO adopted in 1991. At the time of diagnosis the median age was 62 (46-87) years. Twelve (63%) women revealed FIGO stage III-IV, whereas four (21%) and three (16%) patients were diagnosed in stage I and stage II, respectively. Eight (42%) women were nullipara. Histology showed serous-papillary carcinoma, in ten (53%) cases. The 5 year survival rate was 22% for all FIGO stages and 80% for stage I. None of the patients with stage III and IV survived 5 years. Ovarian cancer and primary carcinoma of the fallopian tube are similar in many aspects. Both carcinomas have a similar age distribution, show an increase among nulliparous women, are often of serous papillary histology, have a poor prognosis with stage and residual tumor size as important prognostic factors, and respond initially well to platinum-based chemotherapy. Nevertheless, there appears to be a difference between the two diseases: primary carcinoma of the fallopian tube is more often diagnosed in an earlier stage. This many be due to lower abdominal pain resulting from tubal dilatation and to abnormal bloody-watery discharge. PMID- 11214614 TI - Artificial neural networks and survival prediction in ovarian carcinoma. AB - The standard use of known survival predictors for ovarian cancer in clinical practice are primarily based on disease stage. This does not permit a real individualization of a patient's potential outcome. This study assessed the value of neural networks to refine the prediction of survival based only on information gleaned at primary surgery. The possibility exists that such methods may permit further elucidation of outcome and influence management. PMID- 11214615 TI - Usefulness of PCR in situ hybridization as a technique for morphological detection of human papillomavirus in uterine cervical neoplasia. AB - This study was designed in order to devise fitting conditions in polymerase chain reaction (PCR)-in situ hybridization (ISH) for observing human papillomavirus (HPV) infection morphologically in uterine cervical neoplasias and to compare the detection rates of HPV by PCR-ISH and solution phase PCR (S-PCR) as well as fluorescence ISH (FISH). Tissues were obtained from 23 patients with cervical intraepithelial neoplasia 3, who visited our hospital between 1994 and 1997. To detect HPV-16, a HPVpF forward primer and a HPVp 16 reverse primer were used. Compared with the traditional methods, the PCR-ISH technique performed in this study was contrived as follows. To prevent detachment, the specimens were attached to silane-coated slides at 90 degrees C and successively left at room temperature for 36 hours. In proteopepsis, pepsin was used. PCR products were fixed with 4% paraformaldehyde. PCR-ISH, S-PCR, and FISH showed HPV-16 positivity in 52.2%, 56.5% and 21.7%, respectively. The positive rate of HPV-16 detected by PCR-ISH as well as S-PCR was significantly higher than that by FISH (p<0.01, respectively). There was no significant difference between the positive rates of HPV-16 detected by PCR-ISH and S-PCR. HPV-16 was detected by S-PCR in all 12 specimens in which HPV-16 expression was judged as positive using PCR-ISH. Similarly, HPV-16 was found by PCR-ISH in all five specimens in which HPV-16 expression was regarded as positive using FISH. While the FISH technique detected HPV-16 signals only in the superficial and middle layers of squamous cells, the PCR-ISH technique demonstrated them in all the layers including the parabasal and basal layers. The PCR-ISH technique contrived in this study has a high sensitivity to HPV-16 equal to that of S-PCR. The difference in detection rate and distribution of HPV DNA between PCR-ISH and FISH might suggest that HPV does not infect the superficial layer but rather the parabasal layer. PMID- 11214616 TI - Malignant fibrous histiocytoma of the uterus. AB - A 56-year-old menopausal woman was admitted to hospital because of vaginal spotting of several months duration. The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and omentectomy. On divalving, the uterus showed an ulcerated nodule 8 cm in diameter, protruding into the uterine cavity from the posterior wall. Histologically the tumor had a typical morphology of malignant fibrous histiocytoma (MFH). Multinucleated giant cells were strongly positive for CD 68 alpha antichymotripsin and alpha antitrypsin. Mononuclear cells also showed the same immunohistochemical pattern though less intensive than the giant cells. The cells were uniformly negative for S-100 protein, myoD1, myogenin desmin and actin. Electron microscopical investigation disclosed ultrastructural features compatible with the histiocytic nature of the tumor. Thirty-three months later the patient was free of disease. PMID- 11214617 TI - Differential diagnosis of breast lesions by use of biomagnetic activity and non linear analysis. AB - PURPOSE: Breast cancer mortality rates have not changed during the past 60 years despite significant advances in screening methods. It is tempting therefore to use novel technology in order to better understand breast oncology. In this study we investigated the biomagnetic activity obtained in benign and malignant breast lesions using a single channel biomagnetometer SQUID (Superconducting Quantum Interference Device) in order to assess the method's efficacy in the differential diagnosis of these two types of lesions and its establishment as a screening technique. METHOD: Magnetic recordings were obtained from 21 patients with palpable breast lumps. Of these 11 were invasive carcinomas and 10 were benign breast lesions. We used non-linear analysis to investigate whether there is any biological differentiation in the dynamics in these two types of lesions. RESULTS: High amplitudes characterized the waveform of a malignant breast lesion whereas in benign breast lesions the corresponding amplitudes were low. Using the application of non-linear analysis we observed a clear saturation value for the dimension of malignant breast lesions and no saturation for benign ones. DISCUSSION: Biomagnetic measurements with the SQUID and the application of non linear analysis are promising procedures in assessing and differentiating breast tumors. PMID- 11214618 TI - Invasive condylomatous vulvar carcinoma associated with multifocal low genital tract neoplasia. A case report. AB - Squamous cell carcinoma is a morphologically heterogenous neoplasm of specific histologic entities involved in human papillomavirus infection. The condylomatous types of squamous cell vulvar carcinoma, caused by HPV-16, most often manifest as exophytic papillary tumors mimicking condylomas. PMID- 11214619 TI - Correlations of serum CA125 level and computerized tomography (CT) imaging with laparotomic findings following intraperitoneal chemotherapy in patients with ovarian cancer. AB - The aim of this study was to evaluate the role of serum CA125 levels and computerized tomography (CT) scans in predicting pathologic response of intraperitoneal chemotherapy in patients with ovarian cancer. We prospectively analyzed serum CA125 levels and abdominopelvic CT scans obtained after the completion of intraperitoneal chemotherapy in 52 patients with ovarian cancer and compared the results with subsequent laparotomic findings, which served as the gold standard for statistical analysis. Laparatomy revealed either microscopic or macroscopic residual disease in 20 patients, while 32 patients were completely tumor-free. CA125 levels correlated significantly with laparotomic findings (p=0.003, u=1405). Median CA125 values in patients with residual tumors and in tumor-free patients following intraperitoneal chemotherapy were 14.6 (1-775) and 7.2 (1-37) U/ml, respectively. Although CT-imaging and CA 125 levels had a high specificity (100% and 96.9%, respectively), they showed a low sensitivity rate (50% and 40%, respectively). Similarly, despite high positive predictive values (100% and 88.9%, respectively), the negative predictive values were 76.2% and 72.1%, respectively. CONCLUSION: Although highly specific, CT scans and CA125 levels do not accurately indicate the presence of disease. Due to a high false negative rate, a normal CT scan or a normal CA125 value is not sufficient to replace a laparotomy. PMID- 11214620 TI - A rare case of angiosarcoma of the breast in a man: case report. AB - This is a case report of a 57-year-old man who had primary angiosarcoma of the left breast. Five months after detecting a mass in his breast, he underwent mastectomy with biopsy of the ipsilateral axillary lymph nodes. Three years later, he is still alive without any recurrence. Angiosarcoma of the female breast is rare and exceptional in males. It is a condition with a poor prognosis and there are as yet no established chemotherapeutic regimens. PMID- 11214621 TI - Conservative surgical management of malignant ovarian germ cell tumors: the experience of the Gynecologic Oncology Unit at Ain Shams University. AB - PURPOSE: To evaluate the role of extended surgical staging in patients with malignant ovarian germ cell tumors in the presence of cisplatinum-based combination chemotherapy. MATERIALS & METHODS: 16 patients aged between 13 and 40 years (mean 20.5) diagnosed and treated for malignant ovarian germ cell tumors at the Gynecologic Oncology Unit. Ain Shams University, during the period from May 1994 to October 1999. RESULTS: Six patients were diagnosed with dysgerminoma, six with immature teratoma and four with endodermal sinus tumor. Only seven cases were primarily managed at the unit and were subjected to proper surgical staging as required by FIGO (two in each of the stages IC, IIC and IIIA and one in stage IV). However, the remaining nine cases were referred to the unit, six after having unilateral salpingo-oophorectomy and no surgical staging, one patient after total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH+BSO), and one with recurrent dysgerminoma in the retroperitoneum and mediastinum following suboptimal treatment. None of these cases were surgically re-explored and all including the first six cases were given the standard BEP chemotherapy for 4-6 courses (mean 5.8). Follow-up ranged from 7-72 months (mean 30.5). All patients are alive without any evidence of disease recurrence except for one patient with a stage IIIA immature teratoma who had a local and distant recurrence and is undergoing second-line chemotherapy. All patients have their menstrual function preserved except for three patients; one having 46,XX pure gonadal dysgenesis with a preoperative FSH level of 120 U/l and the eldest two patients having a TAH+BSO as they had completed their families. Three patients are currently pregnant. CONCLUSION: In view of the high chemosensitivity and curability of ovarian germ cell tumors and their occurrence in young patients, every effort should be made to preserve one ovary and the uterus for future reproduction even in advanced cases. The role of revisional surgical staging, in particular retroperitoneal lymphadenectomy in light of these data and those of others should be redefined in the future. PMID- 11214622 TI - Phase II study of high-dose paclitaxel in platinum-refractory epithelial ovarian cancer. AB - The purposes of this study were to determine the efficacy of paclitaxel, using a dose of 200 mg/m2 intravenous continuous infusion over 24 hours every three weeks in the treatement of platinum-refractory epithelial ovarian cancer (EOC) and to evaluate the toxicities. Eligibility criteria included: histologically proven EOC, platinum resistance, measurable disease, Zubrod performance status grade 0 2, expected survival of > 3 months and adequate hematological function. Response was assessed at three-cycle intervals or earlier if required. Twenty-one patients were recruited in this study. The response rate was 52% (2 CR, 9 PR) with a median duration of response of six months. The median progression-free interval was eight months and the median survival was 12 months. Leukopenia was the predominant toxic effect. Eighty-six percent of patients required granulocyte colony stimulation factor (G-CSF). All patients had alopecia grade 3. In conclusion, high-dose paclitaxel is active in platinum-refractory EOC with manageable toxicities. PMID- 11214623 TI - Comparison of granulocyte-colony, stimulating factor and granulocyte macrophage colony stimulating factor in the treatment of chemotherapy extravasation ulcers. AB - The results of perilesional granulocyte macrophage-colony stimulating factor and granulocyte-colony stimulating factor application in a patient with chemotherapy extravasation ulcers are reported. A 64-year-old patient with recurrent ovarian carcinoma was admitted to our department in February 1999. In June 1998, six cycles of chemotherapy were applied to the patient after surgery. At the first cycle, two ulcers appeared on both lower arms related to doxorubicin extravasation despite all interventions. When the patient was admitted to in our department, we observed an ulcer on the distal part of the right lower arm with a dimension of 1.5x2 cm and another on the proximal portion of the left lower arm with a dimension of 2.5x3 cm. Of those ulcers, the bigger and deeper one on the left was treated with weekly 400 mcg granulocyte macrophage-colony stimulating factor subcutaneously for three weeks. The lesion completely disappeared in the fourth week. The other ulcer that was left for control on the right arm was treated with weekly 48 M.U. granulocyte-colony stimulating factor for four weeks. This ulcer did not reduce in size. As a result granulocyte-colony stimulating factor did not affect the healing of chemotherapy extravasation ulcers, as did granulocyte macrophage-stimulating factor. PMID- 11214624 TI - Primary malignant lymphoma of the ovary: an unusual presentation of a rare disease. AB - Because the outcome of patients with primary ovarian non-Hodgkin's lymphoma (NHL) is controversial, we present the incidental finding of a primary malignant lymphoma of the ovary in a 50-year-old patient. Three and a half years following ablative surgery and adjuvant chemotherapy, the patient is alive and disease free. Ovarian lymphoma is a disease of reportedly poor prognosis. However, many previously reported cases of ovarian lymphoma actually represented ovarian involvement by a more diffuse lymphomatous process. If stringent criteria are used for case selection, true primary ovarian lymphoma is a very rare disease and usually carries a favorable prognosis. PMID- 11214625 TI - Thalamic astrocytomas: surgical anatomy and results of a pilot series using maximum microsurgical removal. AB - Deep-seated astrocytomas within the basal ganglia and the thalamus are considered unfavourable for microsurgical removal since the circumferential neighbourhood of critical structures limits radical resection. On closer assessment, the thalamus has a unique configuration within the basal ganglia. Its tetrahedric shape has 3 free surfaces and only the ventrolateral border is in contact with vital and critical functional structures, e.g. the subthalamic nuclei and the internal capsule. The purpose of the present study was to investigate the feasibility of maximum microsurgical removal in a series of intrinsic thalamic astrocytomas. 14 patients with intrathalamic astrocytomas grades I to 4 as diagnosed by previous stereotactic biopsy or intra-operative frozen section were selected for maximum microsurgical removal. The infratentorial supracerebellar approach from the contralateral side was used for 4 limited neoplasms of the pulvinar. For the other 10 larger and more extensive processes a parieto-occipital transventricular approach was chosen. Final histology gave the result of astrocytoma grade 1 or 2 in 4 patients, and of astrocytoma grade 3 or 4 in 10 patients. Postoperative MRI confirmed reduction of the tumor mass by 80 to 100% in 11 of 14 cases. Regional ancillary radiotherapy with 60 Gy was administered postoperatively for astrocytomas grades 3 and 4. Two patients operated on via the posterior transventricular approach had new postoperative partial hemianopia. Five of the 14 patients finally needed a ventriculo-peritoneal shunt. During the follow-up time of 6 to 52 months, tumor progression/recurrence was observed in 6 of the 10 high grade and none of the low grade neoplasms. The present pilot series demonstrates the feasibility of the microsurgical concept. Comparison with other treatment modalities, such as brachytherapy, requires future consideration. PMID- 11214626 TI - Multiple pituitary hormone gradients from cavernous sinus sampling in patients with Cushing's disease. AB - OBJECTIVE: Cavernous sinus sampling in patients with adreno-corticotropic-hormone (ACTH) secreting pituitary adenomas has been used to identify directly ACTH hypersecretion from the pituitary and to predict the lateralization of a microadenoma. In our previous series, cavernous sinus sampling provided a sufficient central/peripheral (c/p) ratio of ACTH and the correct laterality of the pituitary lesion in all microadenomas situated in the lateral wing. To clarify the diagnostic value of other anterior pituitary hormones in relation to ACTH gradients, we evaluated multiple pituitary hormone gradients between a cavernous sinus and a peripheral vein and between both cavernous sinuses in patients with Cushing's disease. METHODS: Cavernous sinus sampling was done in 11 patients with clinical and biochemical features of ACTH-dependent Cushing's syndrome. In 9, pituitary adenoma was detected during trans-sphenoidal surgery and histologically confirmed, while 2 others were suspected of having ectopic lesions. Serum ACTH, prolactin (PRL), thyroid stimulating hormone (TSH), growth hormone (GH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) from catheters in both cavernous sinuses and from a peripheral vein were measured. The c/p ratios of each hormone and the intercavernous gradients were evaluated. RESULTS: The c/p ratio of ACTH indicated the presense of pituitary lesions in all 9 patients with ACTH-secreting microadenomas. In addition, the intercavernous gradients of ACTH indicated the correct localization of microadenomas in all 6 patients with lateralized lesions. As for other hormones, the c/p ratios of GH, PRL, TSH and LH were significantly high in number 7, 6, 6 and 3 patients, respectively. In contrast, the significant step up of FSH was observed only in one patient. The intercavernous gradients of GH and PRL were significantly high in number 5 and 4 patients, respectively. CONCLUSIONS: The intercavernous gradients of GH and PRL tend to indicate the lateralization of a microadenoma. The measurement of GH and PRL during cavernous sinus sampling may provide additional information, in the lateralization of ACTH-secreting microadenomas. PMID- 11214627 TI - Proliferation, vascular endothelial growth factor expression and cavernous sinus invasion in growth hormone secreting pituitary adenomas. AB - Surgical cure of growth hormone producing pituitary adenomas (GHomas) becomes difficult when they invade the cavernous sinus (CS). Tumour proliferative activity and angiogenesis are thought to be required for tumour growth and invasion, and vascular endothelial growth factor (VEGF) activates neovascularization around tumours. In this study, the mechanism and clinical significance of CS invasion is analysed. In 25 surgically treated GHomas, the extent of CS invasion was classified as high (Knosp's grade 3 and 4), and low (grade 0, 1 and 2) MR grades, and the MR grades were compared with tumour proliferative potential (Ki-67 expression), angiogenetic demand (VEGF expression), volume of adenomas and serum hormone levels. The Ki-67 index of high MR grade adenomas (1.17 +/- 0.62%) was significantly higher than that of low MR grade adenomas (0.55 +/- 0.42%, p = 0.027), whereas VEGF expression showed no significant correlation with MR grades (p > 0.999). Tumour volume also showed a significant correlation with MR grade (p = 0.002). VEGF expression was not correlated with serum hormone level and volume, but was correlated with tumour proliferative potential. Proliferative potential and tumour volume were two independent factors related to CS invasion. Although VEGF expression was not a direct factor related to CS invasion, it may indirectly play a role in activation of tumour aggressiveness, which is required in CS invasion. Our results show that high MR grade adenomas have higher proliferative ability. In order to improve the surgical outcome, preoperative medical debulking is indicated, particularly, in such adenomas. PMID- 11214628 TI - Closure of recurrent frontal skull base defects with vascularized flaps -- a technical case report. AB - Techniques for vascularized reconstruction of the anterior cranial fossa floor defects causing recurrent cerebrospinal fluid fistula are discussed in this report. The closure employs the use of local random- or axial-pattern vascularized flaps in simple cases. In complicated cases (for instance, status after repeated exploration) the tissue of the cranial base is severely compromised and shows low potential for healing. Non-vascularized grafts only add avital scars to the already present ones leading to recurrent fistulas. Free vascularized flaps show more mechanical strength and less scar contraction, resistance to infections and survive better in a compromised surrounding, thus leading to long term sealing in such cases. The technical issues of vascularized closure of defects of the frontal skull base are discussed in this report. PMID- 11214629 TI - Surgical treatment of glossopharyngeal neuralgia as vascular compression syndrome via transcondylar fossa (supracondylar transjugular tubercle) approach. AB - OBJECTIVE: These are the first reported cases in whom the transcondylar fossa approach was applied for the treatment of glossopharyngeal neuralgia (GPN) as a vascular compression syndrome. CASES PRESENTATION: All three cases presented with severe paroxysmal pharyngeal pain which could not be controlled by medical treatment. The patients all underwent microvascular decompression surgery (MVD) via transcondylar fossa approach. The posterior inferior cerebellar artery or the anterior inferior cerebellar artery was clearly verified to be compressing the glossopharyngeal nerve and then was safely and completely moved and fixed to the dura mater by the sling retraction technique to effect decompression. No patient has since experienced any further pain or permanent neurological deficit after surgery. TECHNICAL ADVANTAGE: The transcondylar fossa approach is one of the lateral approaches which is different from the transcondylar approach. In this approach, the posterior part of the jugular tubercle is extradurally removed without injuring the atlanto-occipital joint. The entire course of the cisternal portion of the glossopharyngeal nerve can be sufficiently seen with gentle retraction of the cerebellar hemisphere, when using this approach. CONCLUSION: This approach makes the MVD for GPN both effective and safe. PMID- 11214630 TI - Haemorrhagic complication following percutaneous transluminal angioplasty for carotid stenosis. AB - We report 2 cases with haemorrhagic complications following percutaneous transluminal angioplasty (PTA) for carotid stenosis. Computed tomography (CT) scanning of these cases demonstrated diffuse subarachnoid haemorrhage in 1 case, and intracerebral haemorrhage in the other case on the next day after PTA. In the latter case, we measured cerebral blood flow velocity and mean transit time with transcranial doppler (TCD) and dynamic CT scan, which demonstrated remarkable increases in the blood flow velocity and peak height, respectively. From these results, postoperative hyperperfusion was suggested to have caused haemorrhagic complications. PMID- 11214631 TI - Central lumbar disc herniation. AB - A follow-up study which describes the experience of the Department of Neurosurgery in Berne in the treatment of patients with central lumbar disc herniation (CLDH). BACKGROUND DATA: The anatomical position of lumbar disc herniation, in general, does not seem to affect postoperative outcome. However, according to other studies a subgroup of patients with central lumbar disc herniations appears to have poorer results. OBJECTIVES: The aim of the present study was to assess clinical outcome in a recent cohort of patients, to investigate whether there is a difference in outcome with regard to the surgical approach (unilateral vs bilateral) and to compare the postoperative results between the subcategories of CLDH: central massprolaps (CMP) and central contained disc herniation (CCDH). METHODS: Between 1990 and 1997, 40 out of 3150 patients operated on for lumbar disc herniation were diagnosed with CLDH (1.2%). The patients were operated on through unilateral or bilateral fenestrations with microdiscectomy. Recent follow-up studies were obtained by standardized questionnaires. The retrospective investigation was performed by an unbiased observer. RESULTS: Long-term follow-up was available for 34 of the 40 patients (85%) at a mean of 3.3 years. Eight patients had an excellent result (24%), 15 patients a good result (44%), 8 patients a fair (24%) and 3 patients had a poor result (9%). Overall, the operation was considered successful in 68% of patients. There was no statistically significant difference in outcome in patients with CMP as compared with those with CCDH (75% versus 64%). There was also no significant difference for better outcome between bilateral as compared with unilateral approaches. CONCLUSIONS: Postoperative outcome of central lumbar disc herniation (CLDH) is poorer as compared with other types of lumbar disc herniation. The reason seems to be the anatomical position of the disc herniation with a peculiar derangement of the disc architecture. The surgical approach itself or the subcategories of CLDH appear to have only minor impact on postoperative outcome. Interlaminar fenestrations, in general, are appropriate for removal of the disc fragments. PMID- 11214632 TI - External ventricular drainage catheters: effect of surface heparinization on bacterial colonization and infection. AB - Surface heparinization of central venous catheters has earlier been shown to reduce the frequency of bacterial colonization and septicaemia. The present study was undertaken to investigate the benefit of surface heparinization of external ventricular drainage (EVD) catheters in relation to bacterial colonization, as measured by bacterial growth and examination by a 16S-rRNA PCR assay, of catheters and of samples of cerebrospinal fluid (CSF). Ninety-eight heparinized and one hundred unheparinized EVD catheters from the same batch of catheters were used. Twenty point five percent of the heparinized and 22.8% (p = 0.63) of the unheparinized EVD catheters were colonized with bacteria. Culture of CSF, which is the definition of clinical infection in this study, yielded growth in 10.3% of patients with heparinized and in 6.3% (p = 0.18) of those with unheparinized catheters. PCR examination yielded positive signal in 31.3% of patients with heparinized catheters and in 37.7% (p = 0.061) of patients without (CSF and catheters). In the subgroup of patients with subarachnoid haemorrhages, there was a tendency, though not statistically significant, towards a lowered frequency of colonization with 23.1% for heparinized and 33.3% (p = 0.31) for unheparinized catheters. PCR examination did not contribute any further to the diagnostic procedure in the patients concerned. The EVD catheters are skin-penetrating devices and contamination from the skin flora is common. Skin cultures, obtained after skin disinfection and insertion of catheters, showed growth of bacteria in 62% of the patients. PMID- 11214633 TI - Virtual pointer projection of the central sulcus to the outside of the skull using frameless neuronavigation -- accuracy and applications. AB - BACKGROUND: The purpose of this prospective study was to localize the central sulcus by frameless neuronavigation and to project this anatomical structure to the outside of the skull on the skin. This method was analyzed in respect to its practicability, accuracy, and potential applications. METHOD: In 27 patients investigated (28 unaffected hemispheres), the central sulcus was virtually projected to the outside of the skull using frameless neuronavigation and a virtual pointer elongation of 15 or 20 mm. The following parameters were measured on the scalp: 1. the distance between the bregma and the midline junction of the central sulcus, and 2. the angle between the central sulcus and the midline. These dada were compared with measurements based on the original axial MR images of these patients. Finally, a laboratory phantom study was designed in analogy to a patient's examination for estimation of the overall accuracy of the neuronavigation system in the experimental setup used in this study. FINDINGS: Virtual pointer projection of the central sulcus to the outside of the skull using frameless neuronavigation was found to be easily possible. The distance between the bregma and the midline junction of the central sulcus amounted to a mean of 55 mm on the left and 56 mm on the right. The angle between the central sulcus and the midline reached a mean of 63 degrees on the left and 60 degrees on the right. These data confirmed results of other studies with no frameless neuronavigation devices. The phantom study revealed a mean overall inaccuracy of 0.9 mm at a virtual pointer elongation of 15 mm. At a virtual pointer elongation of 20 mm, the mean overall inaccuracy of our study was 1.1 mm. These results correspond to the inaccuracy of frame based stereotaxy. INTERPRETATION: It is easily possible, valid, and reliable to virtually project the central sulcus to the outside of the skull with an acceptably low inaccuracy using frameless neuronavigation. This is important for research studies that correlate and integrate different functional imaging methods with the aid of frameless neuronavigation. PMID- 11214634 TI - From anaesthesia for neurosurgery to neuroanaesthesia: a historical note. PMID- 11214635 TI - Scanning electron microscopic evaluation of nonocclusive excimer laser-assisted anastomosis in rabbits. AB - BACKGROUND: The nonocclusive Excimer laser-assisted bypass technique has been described in previous studies and proved to be a promising bypass operation in vascular brain surgery. Little is known about the morphological regeneration process of the laser-assisted anastomosis in time. By way of a scanning electron microscopic study we examined the way in which the anastomosis site created by the nonocclusive Excimer laser-assisted anastomosis technique becomes endothelialized. METHODS: In 14 rabbits the internal jugular vein was placed in a loop on the abdominal aorta. The distal anastomosis was made using the nonocclusive Excimer laser-assisted technique. The proximal anastomosis was made either laser-assisted or conventional end-to-side. After clipping of the aorta between the two anastomoses sites the vein served as a bypass. To evaluate the endothelialization at the laser-assisted anastomosis site in time, a scanning electron microscopic study was performed. RESULTS: In the first hours after the bypass operation a new intimal surface is formed by fibrin and activated platelets. Some leukocytes are seen during the first days. The endothelialization process of the laser-assisted anastomosis site begins one day after the operation. The gradual endothelialization process evolved along two lines. First, endothelial cells grow from the side of the aorta to the bypass. Second, after one day solitary (blood-borne) endothelial cells deposit on the laser edge and the sutures, covering the platelet aggregates. CONCLUSIONS: The endothelialization of the Excimer laser-assisted anastomosis is more or less completed 9 days after the operation. The edge created by the laser becomes smoother after a few days and is gone for the most part after 9 days. PMID- 11214636 TI - Endothelin-1 initiates the development of vasospasm after subarachnoid haemorrhage through protein kinase C activation, but does not contribute to prolonged vasospasm. AB - Endothelium plays a role in the regulation of vascular tone. Endothelin is a family of potent vasoconstrictive peptides, and endothelin-1 (ET-1) produced in the endothelium induces a tonic contraction via specific receptor ET(A). ET-1 has been postulated as an important factor in the development of vasospasm after subarachnoid haemorrhage (SAH). We have previously shown that protein kinase C (PKC) of the cerebral artery plays a pivotal role in the pathogenesis of vasospasm. The purpose of this study is to clarify the relationship between ET-1 and PKC in the development and maintenance of vasospasm. Using a "two haemorrhage" canine model, chronological changes of angiographic progression of vasospasm, PKC activation, and ET-1 level of the basilar artery were assessed. In an isometric tension study with a control artery, the effects of ET(A)- and ET(A)/ET(B)-antagonists on the tonic contraction induced by ET-1 were examined. The effects of ET-1, ET-1 and an ET(A)-antagonist, and ET-1 and an ET(A)/ET(B) antagonist on PKC activation were also evaluated. ET-1 level temporarily increased, then decreased to the control level in a later stage of vasospasm. ET 1 induced a tonic contraction and enhancement of PKC activation, but both were inhibited either by an ET(A)- or an ET(A)/ET(B)-antagonist. These results indicate that ET-1 initiates the development of vasospasm through PKC activation, but does not contribute to prolonged vasospasm. PMID- 11214637 TI - Central neurocytoma: 2 case reports and review of the literature. AB - Central neurocytoma is a rare benign tumor of the central nervous system occuring in young adults and typically located in the ventricles. The tumor is composed of small round cells with neuronal differentiation and has a favourable prognosis. We report two cases of giant central neurocytomas with a triventricular extension in two young women. The first case concerned a 26 years old righthanded woman in whom an intraventricular mass was discovered, after a car accident with head trauma. Skull radiography showed an enlargment of the sella turcica. A CT scan performed in order to examine the pituitary gland revealed a voluminous and heterogenous intraventricular tumor with calcification. The second case concerned a 26 years old righthanded woman, presenting with a 4 Glasgow Coma Scale Score preceded by an acute onset of headache with projectile vomiting. A CT scan performed in emergency revealed a voluminous intraventricular mass with significant hydrocephalus. We review the different pathological and topographical patterns of previously published neurocytomas and discuss surgical management, effectiveness of radiation therapy and biological behavior. PMID- 11214638 TI - Haemorrhagic nonsecreting pituitary adenoma associated with persistent primitive trigeminal artery. PMID- 11214639 TI - Ruptured intracranial aneurysms in infancy. Diagnostic difficulties and overall reflections associated with the surgical treatment and the treatment of vasospasm. PMID- 11214640 TI - Growth of a meningioma induced by implantation of a foreign body into an arachnoid cyst. PMID- 11214641 TI - Research, publication and ethics. PMID- 11214642 TI - Leptomeningeal contrast enhancement in moyamoya: its potential role in postoperative assessment of circulation through the bypass. AB - Leptomeningeal contrast enhancement (LMCE) is one of the MRI features of moyamoya. Its clinical significance, however, is not elucidated. Our purpose was to characterise LMCE on MRI and to evaluate its role in the assessment of circulation through a surgically established bypass in moyamoya. We studied 16 patients with idiopathic moyamoya (seven males, nine females, includingt four children, aged 7 to 54 years, mean 24 years) who underwent T1-weighted MRI before and after intravenous contrast medium. The presence of LMCE, its intensity and anatomical distribution, catheter angiographic findings, and relation of LMCE to the bypass surgery were assessed. More LMCE was seen in the cerebrum in most patients with moyamoya than in normal controls. LMCE in the brain stem and cerebellum was minimal, similar to that seen in the controls. LMCE was less prominent following surgery than before operation or in patients who did not undergo surgery. In three patients examined both before and after operation LMCE became less prominent following bypass surgery. As LMCE becomes less prominent after "effective" bypass surgery, this may be used for evaluation of effectiveness of surgery in moyamoya. PMID- 11214643 TI - Continuous administration of contrast medium for transcranial colour-coded sonography. AB - Since the introduction of contrast media, transcranial colour-coded sonography (TCCS) has become increasingly important for examination of the intracranial vessels. However, the widely practised bolus injection of these agents leads to initial blooming artefacts and thereafter the level of contrast enhancement decreases rapidly, reducing the effective time of enhancement. It was our aim to investigate the effect of continuous administration of contrast medium at a defined infusion rate. We performed 28 TCCS examinations of the intracranial vessels in 26 patients using a 2.25 MHz phased-array transducer during administration of 4 g Levovist (Schering, Berlin, Germany) 300 mg/ml with a constant infusion rate of 60 ml/h into an antecubital vein. The degree of enhancement was graded over time in a subjective analysis by two independent observers. During continuous administration, a constant level of contrast enhancement was reached after 60.1+/-26.2 s and this lasted 663.4+/-55.8 s as assessed by the first observer (66.6+/-26.2 s and 664.3+/-55.9 s according to the second observer). The limits of inter-observer agreement ranged from -10.1% to 9.9%. No major blooming effect was seen in the initial phase of the examination. PMID- 11214644 TI - Primary central nervous system lymphoma in AIDS: a wider spectrum of CT and MRI findings. AB - Diagnosis of primary central nervous system lymphoma (PCNSL) in patients with AIDS based on radiological findings is still a challenging problem. Our purpose was to review the CT and MRI findings in PCNSL in our patients with AIDS and compare them with those reported in the literature. CT and MRI of 28 patients with AIDS and pathologically confirmed PCNSL were analysed retrospectively for the number of lesions, their site, size, density, signal intensity, contrast enhancement, oedema and mass effect. We found 82 lesions. On CT 45 lesions were found in 22 patients, whereas MRI revealed 66 in 20 patients. The lymphoma was solitary in 20 patients (29 %) and multiple in 20 (71%). Spontaneous haemorrhage was seen in 7 patients. Contrast-enhanced MRI showed no enhancement in 27.3 % (18/66) of the lesions. In one patient diffuse signal abnormalities in the white matter were seen on T2-weighted images. Our findings suggest that the previously described spectrum imaging characteristics of PCNSL has widened. Neuroradiologists should be aware of the variable appearance in patients with AIDS. Spontaneous haemorrhage, a non-enhancing lesion, or diffuse white matter changes do not exclude lymphoma in an immunocompromised patient. PMID- 11214645 TI - Primary brain lymphoma presenting as Parkinson's disease. AB - Neoplasm is an uncommon cause of a parkinsonian syndrome. We report a woman with primary brain B-cell lymphoma presenting as Parkinson's disease. After 1 year of the illness, CT and MRI showed lesions without mass effect in the basal ganglia and corpus callosum. The patient did not respond to levodopa and right cerebellar and brain-stem signs appeared, which prompted further neuroimaging, showing an increase in size of the lesions and a right cerebellar and pontine mass. Stereotactic biopsy of the basal ganglia showed high-grade B-cell lymphoma. Despite the basal ganglia frequently being involved in lymphoma of the brain, presentation with typical or atypical parkinsonism is exceptional. PMID- 11214646 TI - Traumatic atlanto-occipital dislocation: MRI and CT. AB - CT and MRI were employed to help characterize an atlanto-occipital dislocation injury, providing useful information for planning surgical stabilization and directing rehabilitation. PMID- 11214648 TI - Cyst of the ligamentum flavum. AB - We report the case of a patient with sciatica resulting from a cyst of the ligamentum flavum. PMID- 11214647 TI - Trans-sphenoidal encephalocele in association with Dandy-Walker complex and cardiovascular anomalies. AB - We present a case of trans-sphenoidal encephalomeningocele in association with a posterior cranial fossa malformation which fulfils the criteria for the Dandy Walker complex [1]. Congenital cardiovascular defects were also present. An abnormality of neural crest development may be responsible for the combined occurrence of these anomalies. PMID- 11214649 TI - MRI of unusual lesions in the internal auditory canal. AB - We report the MRI findings of six unusual lesions of the internal auditory canal: three haemangiomas, one lipoma, one metastasis and one traumatic neuroma. We compare the findings to those of 20 intracanalicular schwannomas. We noted the site and size of the tumour, its signal intensity, borders and the homogeneity of enhancement were studied on T1-weighted images before and after intravenous contrast medium and T2-weighted images. Most schwannomas were homogeneous lesions, isointense on T1- and T2-weighted images, and strongly enhancing. Spontaneous high signal on T1-weighted images, heterogeneous contrast enhancement and extranodular enhancement were helpful for recognising lesions other then schwannomas; site, size and signal on T2-weighted images were not. All the haemangiomas had a specific pattern of contrast enhancement, with an anterior core intensely enhancing portion and a posterior portion which enhanced moderately or not at all. PMID- 11214650 TI - MRI and CT of adenomatous tumours of the middle ear. AB - We report three adenomatous middle-ear tumours, an adenoma, an adenocarcinoma and a semimalignant adenomatous tumour, with special attention to CT and MRI findings. In all cases we found small intratympanic masses in which the ossicles were embedded. All showed contrast enhancement and similar signal intensity as brain tissue on T1- and T2-weighted images. The biological nature of the tumours was not reflected by the imaging or operative findings. PMID- 11214651 TI - 1H MR spectroscopy evidence for the varied nature of asymptomatic focal brain lesions in neurofibromatosis type 1. AB - We present the MRI and 1H MR spectroscopy findings in six patients with neurofibromatosis type 1 (NF1) and asymptomatic focal brain lesions. Variations in imaging appearances were seen, including regression of a previously identified lesion. MR spectra for the lesions and corresponding areas of normal brain show significant differences. The lesions could be separated into two groups, one demonstrating only slight metabolite ratio changes relative to normal brain and the other group showing significant increase in choline and decrease in N-acetyl aspartate. The lesion which regressed fell into the second group. These findings are not in agreement with those previously reported and provide evidence for the varied and possibly transient nature of these asymptomatic lesions. The spectroscopy findings suggest that metabolite changes may be present without visible changes on MRI. PMID- 11214652 TI - Fetal germinal matrix and intraventricular haemorrhage diagnosed by MRI. AB - Subependymal germinal matrix haemorrhage and intraventricular haemorrhage (GMIVH) is a common complication of delivery in preterm neonates but has rarely been observed in the fetus. We report two cases of GMIVH in fetuses of 36 weeks gestation, clearly demonstrated by antenatal MRI. In both cases progressive ventriculomegaly was observed, and ventriculoperitoneal shunts were placed at 19 and 6 months of age, respectively. Prenatal GMIVH may be a cause of congenital hydrocephalus, for which no aetiology has yet been found. PMID- 11214653 TI - Monitoring cerebral perfusion after subarachnoid hemorrhage using CT. AB - The aim of this prospective study was to assess the feasibility and diagnostic relevance of repetitive dynamic (contrast-enhanced) CT measurements of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) in the first 3 weeks after aneurysmal subarachnoid hemorrhage (SAH). In 15 patients with SAH, 59 dynamic CT studies including 944 regions of interest (ROI) were analyzed. The results were correlated with the clinical course and time after the event and the occurrence of vasospasm. Values for the entire series were 33.8+/-19.3 ml/100 g/min (CBF), 3.3+/-1.3 ml/100 g (CBV), and 7.3+/-3.9 s (MTT). Significant differences in CBF and CBV were found between ROI in grey and white matter, with time after the event, between patients with significant and absent or minor vasospasm, and between patients with and without a presumed vasospasm-related infarct. PMID- 11214654 TI - Dysembryoplastic neuroepithelial tumour and cerebellar atrophy: case report. AB - Dysembryoplastic neuroepithelial tumours (DNET) are mainly benign cortical lesions. DNET in the caudate nucleus, thalamus, hypothalamus, pons and cerebellar hemispheres has also been reported. We describe a fronto-temporo-parietal DNET extending to the ipsilateral thalamus and internal capsule, associated with cerebellar lobe atrophy. Involvement of the internal capsule and complication of DNET with cerebellar atrophy have not been reported previously. We emphasise the importance of early diagnosis and treatment of this rare condition. PMID- 11214655 TI - The mechanism of thallium-201 accumulation. PMID- 11214656 TI - Guidelines for the diagnosis of dementia and Alzheimer's disease. The Dementia Study Group of the Italian Neurological Society. PMID- 11214657 TI - Transesophageal echocardiography for identifying potential cardiac sources of embolism in patients with stroke. AB - Pathologies of cerebral circulation are one of the most frequent causes of mortality and morbidity among the populations of Western countries. The incidence of ischemic events presumed to have a cardioembolic origin varies from 13% to 34% in the largest international multi-center studies. However, some authors have reported an incidence of general cardiogenic stroke ranging from 23% to 36% in younger patients. Transesophageal echocardiography (TEE) is a useful investigation for identifying cardiac sources of embolism in patients without vascular alterations involving the carotid and vertebral districts. This study comprised 73 patients with unexplained stroke who were investigated by both transthoracic echocardiography (TTE) and TEE. Vascular echocolor sonography had been performed in all of them with negative results. TEE demonstrated: atrial or ventricular thrombosis in 6 patients (8%), intracavitary neoplasm in 2 (2%), spontaneous echocontrast in 11 (13%), valve strands in 6 (7%), complex aortic plaque in 10 (11%), patency of the foramen ovale in 17 (19%), atrial septal aneurysm in 9 (11%), dystrophy and mitral calcifications in 9 (11%). In the other 18 patients, TEE did not reveal any anomalies. Definite sources of stroke (clots and tumors) were identified in 14% of all the lesions; however, the majority (86%) were potential sources. A comparison of the two echocardiographic techniques demonstrated a greater sensitivity and specificity of TEE. Although TEE was superior to TTE for identifying and evaluating potential embolic sources, we found both methods to be useful and would advise performing TTE before TEE. While TTE is not capable of identifying the majority of anomalies, it does provide useful information to guide subsequent transesophageal investigations. PMID- 11214658 TI - Conventional external radiotherapy in the management of clivus chordomas with overt residual disease. AB - Cranial chordomas are uncommon tumors accounting for less than 1% of all intracranial neoplasms. Although they are slowly growing, rarely metastasizing tumors, cranial chordomas are challenging to treat due to their critical location, invasive nature and aggressive recurrence. The aim of this retrospective study was to evaluate the role of conventional irradiation in the treatment of clival chordomas with overt residual disease after incomplete surgery. Between January 1979 and December 1997, 18 patients with histologically confirmed clival chordoma were treated with radiotherapy. Median age at the time of diagnosis was 32 years. The mean duration of the symptoms before diagnosis was 33.9 months. Median tumor diameter at initial presentation was 5 cm (range, 3-7 cm). The type of surgical procedure was subtotal excision in 11 patients and biopsy in 7. Radiation treatment was delivered with megavoltage units, and total doses between 50 Gy and 64 Gy (median, 60 Gy) were administered with conventional daily fractions. One patient received additional 12.50 Gy with linear accelerator based stereotactic radiosurgery after subtotal excision and external irradiation. The mean follow-up time was 43.2 months. Overall survival at 5 years was 35%. Eleven patients showed progression after radiotherapy. The median time to progression after radiotherapy was 40.8 months (38.4-43.2) with a 5-year progression-free survival of 23%. Five patients (29.4%) showed symptomatic relief after radiotherapy while persistent symptoms were recorded for 6 patients. Incomplete surgery and conventional external radiotherapy with a dose of around 60 Gy seem to be inadequate in the treatment of clival chordomas. PMID- 11214659 TI - Leucopenia induced by low dose clozapine in Parkinson's disease recedes shortly after drug withdrawal. Clinical case descriptions with commentary on switch-over to olanzapine. AB - Four patients affected by severe Parkinson's disease developed leucopenia (900 1200 WBC) during treatment of psychosis (3) or untreatable insomnia (1) with clozapine (37.5-75 mg/day). Clozapine withdrawal was followed by recovery of leucopenia (4000-6000 WBC) in two weeks with no need for the administration of leucokines. After 1-6 months olanzapine was administered (increasing the dose from 2.5 to 10 mg/day) to treat persisting disturbances, but the drug induced severe worsening of parkinsonism and also this drug had to be withdrawn. PMID- 11214660 TI - EDSS correlated analysis of median nerve somatosensory evoked potentials in multiple sclerosis. AB - Median nerve somatosensory evoked potentials (SEP) were recorded in 30 patients with multiple sclerosis. The examined patients had an expanded disability status scale (EDSS) between 0 and 6. The primary cortical potential N20, the subcortical potentials P14, N13b, N13a and the peripheral potential P9 were recorded simultaneously. In 5 patients normal SEP were observed (group 1), and in 6 patients there were consecutive disturbances of the somatosensory pathway (group 3). In 19 patients subcortical potentials were abnormal or absent while the following potentials were normal or identified which pattern corresponds to amplification within CNS structures (group 2). The EDSS of groups 1 and 2 were similar and lower than the EDSS of group 3, which indicates that amplification mechanisms could represent a positive prognostic factor in SEP diagnosis of multiple sclerosis. PMID- 11214661 TI - Length of hospitalization of patients with transient ischemic attacks. AB - OBJECTIVE: To investigate factors that influence length of stay (LOS) in patients hospitalized for transient ischemic attacks (TIAs). This may help to reduce unnecessary days of hospitalization. DESIGN: Retrospective study. SETTING: A large, non-academic general hospital. PATIENTS: All patients hospitalized for TIAs during the years 1996-1998 were retrospectively studied. We analyzed the relationship between demographic, clinical and management features and LOS. RESULTS: We studied 157 patients. Median LOS was 8 days (range, 1 to 21 days). Statistical analysis showed that female sex, being hospitalized in 1996, hospitalization from Wednesday through Saturday, and second-level cardiological, neuroradiological and miscellaneous investigations significantly increased LOS. CONCLUSIONS: The LOS of patients with TIAs may be reduced through measures that accelerate the diagnostic work-up and by scheduling the admission to the first days of the week, when this is possibile. PMID- 11214662 TI - Guillain-Barre syndrome: an Italian multicentre case-control study. Guillain Barre Syndrome Study Group. AB - Various diseases are described as antecedents of Guillain-Barre syndrome (GBS), particularly gastroenteritis and respiratory infectious diseases, but epidemiological surveys are rare. This paper details a multicentre matched case control study carried out within a well-defined Italian population. For each GBS case fulfilling the Asbury and Cornblath criteria, one control was recruited from a neurological (NC) ward and another from a non-neurological (NNC) ward, matched for age, sex, season of disease onset and area of residence. All cases and controls were administered a semistructured questionnaire. The OR was calculated according to the Mantel-Haenszel equation for triplets. Between 1 October 1996 and 30 September 1998, 75 triplets were included in the case-control study. The OR for flu-like syndrome was 7.14 (CI 95%, 3.28-15.52) and for gastroenteritis 3.57 (CI 95%, 1.31-9.72); no other factor reached significance. Our results, based on the clinical and anamnestic features of triplets of patients, support the possible role as risk factors for GBS of infectious diseases, particularly flu-like syndrome and gastroenteritis. PMID- 11214663 TI - Plasma levels of coagulation and fibrinolysis markers in acute ischemic stroke patients with lone atrial fibrillation. AB - Atrial fibrillation (AF) is a well-defined risk factor for ischemic stroke. Patients with lone AF represent a subgroup of AF patients with the lowest lifelong stroke risk. Nonvalvular atrial fibrillation (NVAF) confers a hypercoagulable state resulting in an increased risk of thromboembolism. This study was performed to determine the contributory role of alteration in the hemostatic markers of thrombin generation and fibrinolysis in patients with lone AF during acute ischemic stroke episode. We studied thrombin-antithrombin complexes (TAT), prothrombin fragments 1+2 (F1+2), tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor type-1 (PAI-1) concentrations in patients with acute middle cerebral artery ischemic stroke due to atherosclerotic large artery disease (n=50), lone AF (n=24) and cardioembolism (n=21). The values were compared with those of age-matched control subjects with lone AF and sinus rhythm (n=21 and 15, respectively). The mean F1+2 concentration was higher in the control subjects with lone AF in comparison with those without AF (p=0.014). Patients with stroke due to possible cardioembolism, from lone AF or other causes, had higher TAT (and marginally higher F1+2) concentrations than those with atherosclerotic stroke (p<0.001). tPA concentrations were not different among groups (p=0.89). PAI-I levels were marginally higher in stroke patients with lone AF and atherothrombotic large artery disease compared to the controls without AF (p=0.05). These results suggest that in the acute period of ischemic stroke secondary to lone AF, enhancement of the coagulatory activity occurs as a result of increased thrombin generation, similar to other possible sources of cardioembolism. Observed hemostatic alterations in acute ischemic stroke associated with lone AF may indicate some therapeutic and prognostic implications. PMID- 11214664 TI - Brachial plexus neuropathy as unusual onset of diffuse neurolymphomatosis. AB - We present a patient with a large B cell gastric lymphoma in total remission who, after 4 months, developed a fatal progressive peripheral neuropathy with an unusual early involvement of the right brachial plexus. No evidence of lymphoma was found at whole body computed tomography, magnetic resonance imaging of the head, cervical spine and right brachial plexus, bone marrow biopsy or repeated lumbar punctures. The diagnosis of neurolymphomatosis was made only at postmortem examination. PMID- 11214665 TI - Eyelid myoclonia with absences in three subjects with mental retardation. AB - Eyelid myoclonia with absences is a rare epileptic syndrome, characterized by eyelid myoclonia, absences, and photosensitivity. On the basis of its clinical and EEG features, this syndrome has been classified as a specific new entity among the idiopathic generalized epilepsies. We report three subjects, aged 4, 16, and 31 years, respectively, with eyelid myoclonia, and absences, mental retardation and other abnormalities of the central nervous system. Our findings suggest that, at least in some cases, eyelid myoclonia and absences can represent a peculiar phenomenon of symptomatic epilepsies. PMID- 11214666 TI - The insomnia plague: a Gabriel Garcia Marquez story. AB - "All the great writers have good eyes" is a sentence by V. Nabokov that is very suitable for G.G. Marquez and his One Hundred Years of Solitude. The novel, published in 1967, introduces among many others, the character of little Rebeca, whose frailness and greenish skin revealed hunger "that was older than she was". The girl, because of a pica syndrome, only liked to eat earth and the cake of whitewash. But her fate appears to be determined by the lethal insomnia plague, whose most fearsome part was not the impossibility of sleeping but its inexorable evolution toward a loss of memory in which the sick person "sinks into a kind of idiocy that had no past". Rebeca's lethal insomnia looks quite similar to the "peculiar, fatal disorder of sleep" originally described by Lugaresi et al. in 1986. One Hundred Years (of Solitude shows that G.G. Marquez was gifted not only with good eyes, but has the seductive power of changing reality into fantasy, while transforming his visions into reality. PMID- 11214667 TI - Biochemical characterization of Mycoplasma bovirhinis, Mycoplasma dispar and recent bovine isolates of Mycoplasma canis. AB - The pattern and kinetics of substrate utilization by the type strains of Mycoplasma canis, M. bovirhinis and M. dispar and ten recent M. canis isolates from cattle were determined. Metabolism of a range of sugars and organic acids by M. dispar was detectable by measurement of oxygen uptake. Organic acids were not utilized by M. bovirhinis or M. canis, and there was no oxygen uptake during metabolism of glucose or other sugars, as monitored by a pH-change method. The M. canis strains varied in their ability to metabolize sugars; seven of the isolates from cattle had the distinctive ability to metabolize sucrose, and one isolate, plus the type strain (from a dog), metabolized N-acetylglucosamine. The M. bovirhinis strain metabolized maltose. However, all the test strains oxidized glycerol at high rates and with a high affinity. Oxidation of glycerol has been reported for other mycoplasmas from the bovine respiratory tract and leads to the production of hydrogen peroxide, a potential virulence factor. PMID- 11214669 TI - Reduction in serum lecithin:cholesterol acyltransferase activity in natural cases of pneumonia in calves. AB - In experimental calf pneumonia induced by inoculations of Pasteurella haemolytica or bovine herpesvirus-1, lipoprotein lipid concentrations and lecithin:cholesterol acyltransferase (LCAT) activity decrease. The purpose of this study was to examine whether similar changes in lipoproteins occur in natural cases of calf pneumonia. When monitored in a time-course study, the activity of LCAT, and the concentrations of free cholesterol, cholesteryl esters, phospholipids and triglycerides were steadily decreased. No significant decreases in LCAT activity or lipid concentrations were detected in sera from cows with mastitis. These results, coupled with the previous findings on experimental calf pneumonia, indicate that, while decreases in LCAT activity and the LCAT-related lipid concentrations are involved in the pathogenesis of calf pneumonia, this is not the case for all inflammatory diseases. PMID- 11214668 TI - Occurrence and characterization of Escherichia coli O157 isolated from cattle in Norway. AB - Faecal samples from 504 imported beef cattle were screened to investigate the occurrence of Escherichia coli O157. The results were compared with those from a previous screening of Norwegian dairy cattle, and the occurrence was found to be higher in the imported beef cattle. The E. coli O157 isolates from the previous and present studies were characterized for the genes encoding for shigatoxin 1 (stx1), shigatoxin 2 (stx2), the intimin protein (eae) and the flagellar protein H7 (fliC) using PCR analysis, pulsed-field gel electrophoresis (PFGE) with the restriction enzyme XbaI, and bacteriophage lambda RFLP analysis using the PvuII restriction enzyme. The isolates from the dairy and beef cattle could be distinguished by the profiles of the toxin genes and by PFGE patterns. Whether the importation of animals in itself should be regarded as a risk factor for the occurrence of E. coli O157, or whether other management factors contribute to the differences in carrier rates compared to the previous study on domestic cattle, is discussed. PMID- 11214670 TI - Glycoconjugate histochemistry in the duodenum of fetal and adult fallow deer. AB - This work aimed to characterize the complex carbohydrates in the duodenum of fetal and adult fallow deer. The proximal parts of the duodenum were removed from the intestine of 12- and 16-week-old fetuses and of adult fallow deer. Sections were assessed by conventional carbohydrate histochemistry combined with glycosidase digestions and treatment with KOH. During development, there was an increase in the acid carboxylated components of the glycoconjugates in goblet cells, while the duodenal glands expressed high quantities of sulphated glycoconjugates at the beginning of development but, in the adult. mainly secreted neutral and carboxylated glycoconjugates containing sialic acid. Sulphated components, probably represented by chondroitin sulphate B-like and heparan sulphate-like glycosaminoglycans may play a role in the morphofunctional differentiation of the duodenum. PMID- 11214671 TI - Antibody response in sheep following immunization with Streptococcus bovis in different adjuvants. AB - Recent studies have shown that immunization with Streptococcus bovis using Freund's complete adjuvant (FCA) may confer protection against lactic acidosis in sheep. The major objective of this study was to compare the antibody responses to S. bovis in a practically acceptable adjuvant (Freund's incomplete adjuvant (FIA); QuilA; dextran sulphate (Dex); Imject Alum; or Gerbu) and in FCA. Thirty five sheep were randomly allocated to 7 treatment groups. Six groups were immunized with S. bovis in an adjuvant; the other group served as the non immunization control. The primary immunization was administered intramuscularly on day 0. followed by a booster injection on day 28. Immunization with FCA induced the highest saliva and serum antibody responses. The saliva antibody concentrations in the FIA and QuilA groups were significantly higher than those in the Alum, Dex and Gerbu groups (p < 0.01). The serum antibody concentration in the FIA group was significantly higher than those in the QuilA, Alum. Dex and Gerbu groups (p < 0.01). Immunization enhanced the antibody level in faeces (p < 0.05), but there was no significant difference between the different adjuvant groups (p > 0.05). Seven and 14 days following booster immunization, the saliva antibody levels induced by QuilA and/or FIA were comparable with the level stimulated by FCA (p > 0.05). There was a strongly positive correlation (R2 = 0.770, p < 0.01) between the antibody concentrations in salival and serum. Compared with the controls, a higher faecal dry matter content was observed in the animals immunized with either FCA or QuilA. The change in faecal dry matter content was positively associated with the faecal antibody concentration (R2 = 0.441, p < 0.05). These results indicate that FIA and QuilA were effective at inducing high levels of antibody responses to S. bovis, and suggest that either Freund's incomplete adjuvant or QuilA may be useful for preparing a practically acceptable vaccine against lactic acidosis. PMID- 11214672 TI - Enhanced lipid peroxide levels in the erythrocytes of calves with haemoglobinuria. AB - Eight 6-9 month old calves, showing clinical signs of intermittent haemoglobinuria, even after treatment with an antipiroplasmal drug (4,4 diamidinodiazaminobenzene diaceturate), were examined for oxidative damage to their erythrocytes and the presence of hemoprotozoa in blood smears. Four calves without signs of haemoglobinuria served as controls. The blood smears from three of the eight calves contained piroplasms for Theileria annulata. Irrespective of the presence of piroplasms in their blood smears, the calves with haemoglobinuria had significantly (p < 0.01) lower haemoglobin concentrations (Hb) and packed cell volumes (PCV). The lipid peroxide level in the erythrocytes, but not in the plasma, of calves with red urine was significantly (p <0.05) higher than that for the controls. It is concluded that haemoglobinuria, irrespective of the presence of piroplasms in blood smears, is associated with oxidative stress to erythrocytes and peroxidation of polyunsaturated fatty acids of cell membrane. PMID- 11214673 TI - A preliminary study on the anthelmintic activity of Calotropis procera latex against Haemonchus contortus infection in Najdi sheep. AB - The anthelmintic activity of Calotropis procera latex was investigated in sheep that had been infected with single oral doses of 12000 infective Haemonchus contortus larvae. Inappetence, dullness, erosive abomasitis, decreased haemoglobin concentration and increased eosinophils were the main features of haemonchosis in the sheep. In the sheep treated with single oral doses of 0.01 ml or 0.02 ml/kg body weight of C. procera latex, egg production was significantly reduced, but not completely suppressed, and fewer adult Haemonchus worms were found in the abomasum. Although the appetite improved, the haemoglobin concentration and serum copper, iron and zinc levels were still reduced after therapy with Calotropis latex. Calotropis latex showed a concentration-dependent larvicidal activity in vitro within 20 min of application. PMID- 11214674 TI - Ethnoveterinary medicine in the Northern Provinces of Cameroon. PMID- 11214675 TI - Detection and differentiation of CAV-1 and CAV-2 by polymerase chain reaction. AB - Canine adenovirus type 1 (CAV-1) and type 2 (CAV-2) can be categorized in the laboratory by haemagglutination and neutralization tests, but they are difficult to differentiate from each other in specimens, especially when infection occurs in the digestive tract. The object of this study was to develop a simple method of detecting and differentiating them. One pair of common primers was designed and synthesized according to the sequences of the E3 and flanking regions and a polymerase chain reaction (PCR) assay was established using these two primers to amplify the virus-specific DNA fragment from clinical specimens as well as from cell cultures. After elecctrophoresis, under the same amplification conditions, 508 bp and 1030 bp PCR products were observed for CAV-1 and CAV-2, respectively. These were further shown to be adenovirus specific by dot hybridization and sequencing. As only one pair of primers was involved in the PCR procedure, it was faster and easier to perform than any of the other assays used for detecting canine adenovirus, making it applicable in the rapid confirmation of diagnosis and differentiation of the two types of canine adenoviruses. PMID- 11214676 TI - Hepatic veno-occlusive disease in children undergoing bone-marrow transplantation: usefulness of sonographic findings. AB - BACKGROUND: Reports of the usefulness of ultrasonography in the diagnosis of hepatic veno-occlusive disease (HVOD) have presented conflicting results. OBJECTIVE: To determine the usefulness of gray-scale or Doppler ultrasonographic measurements in the diagnosis of HVOD in pediatric patients undergoing BMT. MATERIALS AND METHODS: We prospectively obtained 202 serial sonograms on 48 patients and examined the association between the clinical diagnosis of HVOD (McDonald criteria) and eight ultrasound parameters, including the hepatic artery resistive index (HARI), direction and velocity of portal venous flow, and thickness of the gall bladder wall. RESULTS: HVOD developed in 29 of the 48 patients. The portal venous velocity increased after BMT in the group without HVOD and decreased in the group with HVOD; this difference was significant (P = 0.01). However, there was a great deal of variability in velocity measurements for individual patients. The mean HARI was 0.64 in the group with HVOD and 0.63 in the group without HVOD, and there was no difference between the two groups in the pattern of change in HARI relative to the day of BMT (P = 0.4). There was also no significant difference in thickness of the gallbladder wall between the two groups (P = 0.6). CONCLUSION: No ultrasound parameter studied was as useful as the McDonald criteria for diagnosing HVOD. PMID- 11214677 TI - Imaging diagnosis of retroperitoneal ganglioneuroma in childhood. AB - PURPOSE: To demonstrate the typical appearance of retroperitoneal ganglioneuromas on CT and MRI. MATERIALS AND METHODS: Retrospective analysis of diagnostic imaging (five CT scans, three MRI scans) in five children aged 3-15 years with the histological diagnosis of ganglioneuroma. RESULTS: The scans showed large (maximum 11 cm diameter), round or oval tumours with sharply defined margins. Intraspinal tumour involvement occurred in two cases. Comparing CTwith MRI, MRI was more accurate in defining the intraspinal involvement. The ganglioneuromas were hypodense on unenhanced CT and showed moderate enhancement with administration of contrast medium. In three patients, CT demonstrated tumour calcification with a disseminated speckled pattern. On T1-weighted MRI the tumours were homogeneous and hypointense, showing marked enhancement after gadolinium administration. On T2-weighted scans the tumours were hyperintense. CONCLUSION: At the time of diagnosis, retroperitoneal ganglioneuromas are generally large tumours that can be shown well by CT and MRI. The appearance on CT more readily suggests the diagnosis, but MRI is superior for documenting local or intraspinal tumour extension and lacks radiation load. PMID- 11214678 TI - Symptomatic splenic hamartoma with renal, cutaneous, and hematological abnormalities. AB - BACKGROUND: There is a rare association between splenic hamartomas and hematological abnormalities with, to our knowledge, only 24 reported cases in the English literature. PATIENTS AND METHODS: We report a case of a splenic hamartoma in a 14-year-old boy associated with membranoproliferative glomerulonephritis, multiple lobular capillary hemangiomas of the skin, hypertension, and anemia. Following imaging with ultrasonography, MRI, and nuclear scans, a hamartoma was suspected, but malignancy could not be excluded. The lesion was removed by partial splenectomy, and pathological examination confirmed the presence of a red pulp splenic hamartoma. RESULTS: The renal, hematological, and dermatological abnormalities resolved following removal of the splenic hamartoma. This is the first reported case of a splenic hamartoma associated with renal, cutaneous, and hematological abnormalities and only the second reported case of a symptomatic splenic hamartoma treated by partial splenectomy. PMID- 11214679 TI - Mucormycosis resulting in a pseudoaneurysm in the spleen. AB - Mucormycosis is an uncommon and frequently fatal fungal infection. It characteristically affects patients with diabetes mellitus or patients with severe immunosuppression. The hallmark of mucormycosis infection is tissue infarction and vascular invasion. We present clinical data and imaging studies of a 16 year-old child with acute lymphoblastic leukemia complicated by disseminated mucormycosis resulting in a pseudoaneurysm of the spleen. This was successfully managed by a combination of systemic antifungal therapy (Amphotericin B) and surgery (splenectomy). This entity has not been described in the literature. PMID- 11214680 TI - Peripheral primitive neuroectodermal tumour of the kidney: CT findings. AB - Peripheral primitive neuroectodermal tumour in the kidney is a rare entity with high malignant potential. The distinctive demographic, clinical and radiological findings, as described in the present case, should suggest this aggressive tumour in the differential diagnosis of renal neoplasms in adolescents. PMID- 11214682 TI - Moyamoya disease and sagittal sinus thrombosis in a child with Down's syndrome. AB - A girl with Down's syndrome, moyamoya disease and sagittal sinus thrombosis is described. She was diagnosed after acute neurological deterioration by MRI and angiography. Recombinant tissue plasminogen activator (r-TPA) was injected locally to recanalise the thrombus. The patient's condition significantly improved and she was discharged. After 2 years of follow-up the child remains asymptomatic. Moyamoya syndrome and cerebral venous thrombosis should not be overlooked as a cause of acute neurological deterioration in a child with Down's syndrome. MRA appears to be a safe and accurate alternative to traditional angiography for the diagnosis of moyamoya disease. Local fibrinolysis with r-TPA is the treatment of choice for cerebral venous thrombosis due to its safety and efficacy. PMID- 11214681 TI - Extrinsic ureteropelvic junction obstruction from a crossing renal vessel: demography and imaging. AB - BACKGROUND: The increase in the use of prenatal ultrasound has revolutionized the detection of hydronephrosis and has had an unanticipated consequence. OBJECTIVE: To describe the new demographics of symptomatic ureteropelvic junction (UPJ) obstruction and the characteristic imaging findings, when the obstruction is extrinsic, from a crossing renal vessel. MATERIALS AND METHODS: From a uroradiology database (1994 through 1999) we identified children with surgically corrected UPJ obstruction from intrinsic and extrinsic causes. RESULTS: One hundred children had symptomatic UPJ obstruction treated by surgery. In 51 (49 %), obstruction was due to a crossing vessel. One hundred and one had UPJ obstruction detected by prenatal sonography. Only 11 (11%) were due to a vessel. Two clinical and imaging findings were strongly suggestive of obstruction from a vessel: (1) in 5 of the 100 children the symptoms (pain, nausea, and vomiting) were intermittent. Only when symptoms were present were there hydronephrosis and obstruction; (2) in 51 of the 100 children a short segment of ureter, just below the UPJ, was filled with contrast or urine (on renal sonography, intravenous urography, or retrograde/antegrade ureterography). CONCLUSIONS: Extrinsic UPJ obstruction caused by a vessel is an uncommon cause of obstruction when all patients are considered. However, in symptomatic older patients whose hydronephrosis was not first identified on prenatal sonography, a vessel was the cause of obstruction in one half. PMID- 11214684 TI - Additional cases of pseudotumoral eosinophilic cystitis. PMID- 11214683 TI - Asymptomatic intraventricular lipid leak from a primary pineal teratoma. AB - We present a case of pineal teratoma in a symptomatically stable 6-year-old child in which MRI revealed intraventricular lipid accumulation in the absence of any primary tumour growth, metastatic disease or tumour degeneration. PMID- 11214685 TI - Internal jugular vein phlebectasia and duplication: case report with magnetic resonance angiography features. PMID- 11214686 TI - Three-dimensional MR microscopy of a transgenic mouse model of dilated cardiomyopathy. AB - BACKGROUND: Scientists are now able to alter the genetics of vertebrate embryos routinely to produce animal models of human developmental diseases. However, our understanding of structural changes in these animal models is limited by current methodologies. Histological techniques, although providing great anatomic detail, display only "static" data (one time point only) in two dimensions. Ultrasound may be used to generate continuous time course data, but is limited by interobserver variation, limited acoustic windows, and relatively low resolution. OBJECTIVE: To apply the high resolution, non-destructive, and three-dimensional acquisition capabilities of magnetic resonance (MR) microscopy to compare the hearts of normal mice versus an established transgenic mouse model of dilated cardiomyopathy. MATERIALS AND METHODS: Transgenic mice exhibiting dilated cardiomyopathy were developed via the introduction of a mutated, heart-specific gene (myosin light chain). Postmortem cardiac imaging was performed on the transgenic mice and normal controls. MR imaging was performed on a Bruker 3T imaging magnet using a custom radiofrequency coil following contrast perfusion of the atrial and ventricular chambers. Image resolution was 156 microm isotropic voxels. MR images were compared to gross pathologic specimens. Imaging data were post-processed using custom software to calculate the volumes of the atria and ventricles and to display the three-dimensional morphology of the chambers and myocardium. RESULTS: Of the seven mice scanned, four exhibited normal right atrial (average = 14.8 microl +/- 1.4), left atrial (average = 8.5 microl +/ 0.3), right ventricular (average = 12.9 microl +/-2.7), and left ventricular (average 3.3 microl +/-0.5) volumes. Three mice exhibited dilatation of the right and left cardiac chambers (RA average = 23.9 microl +/-5.6; LA average = 15.9 microl +/-4.8; RV average = 32.5 microl +/- 6.8; LV average 24.0 microl +/-1.4). The gross morphology was verified upon autopsy of the animals and correlated with the animal's genotype. The differences in volumes between the normal and dilated cardiomyopathy mice were statistically significant (P values ranged from 0.001 to 0.024 for the different chambers). CONCLUSION: MR microscopy is a potentially useful tool for developmental biology research. The imaging of mouse hearts is feasible, and these methods provide quantitative and qualitative morphologic data of a mouse model of dilated cardiomyopathy not available using traditional methods. PMID- 11214687 TI - Complications of limb-sparing procedures using endoprosthetic replacements about the knee for pediatric skeletal sarcomas. AB - Ninety-five percent of bone tumors are now managed with limb-sparing techniques. For pediatric patients with bone cancer, such limb reconstruction techniques often involve the placement of large endoprosthetic devices with the goal of improving survivors' quality of life. Nevertheless, few radiologic publications discuss the use of these techniques in children and adolescents. This pictorial essay describes the imaging characteristics of the complications associated with endoprosthetic devices and discusses the conditions that may simulate them. PMID- 11214688 TI - Vertebral osteoid osteoma masquerading as a malignant bone or soft-tissue tumor on MRI. AB - PURPOSE: Four pediatric patients were sent to our institution with the diagnosis of soft-tissue/malignant bone tumor. In all cases an MRI was the initial study performed for neck or back pain. All were surgically proven to have an osteoid osteoma/osteoblastoma (OO) as a final diagnosis. The MRI findings are reviewed. METHODS: Four patients, three boys and one girl, ranging in age from 5 to 17 years, presented with symptoms of neck or back pain for 2 months to 2 years. Two had neurological findings. All patients underwent MRI. RESULTS: All MRIs demonstrated decreased T1 signal and increased T2 signal in the soft tissues and bone surrounding the lesions consistent with edema. Enhancement was observed in the adjacent soft tissues and in the lesion nidus retrospectively. CONCLUSION: Investigating neck or back pain with an initial MRI may lead to misleading diagnoses unless the radiologist is aware of the typical MRI appearance of vertebral osteoid osteoma. PMID- 11214689 TI - Spondylar dysplasia in type X collagenopathy. AB - BACKGROUND: The type X collagen gene (COL10A1) is currently known as the disease causing gene of metaphyseal dysplasia type Schmid (MDS), whereas a mutation of COL10A1 has been reported to cosegregate with a disease phenotype of mild spondylometaphyseal dysplasia (SMD) in a Japanese family. OBJECTIVE: To elucidate whether or not spondylar dysplasia is common in patients with mutations of COL10A1. MATERIALS AND METHODS: We re-evaluated the radiological manifestations in six patients with mutations of COL10A1, who had been previously reported as having MDS. RESULTS: Two of six patients showed mild platyspondyly in infancy and early childhood. In both patients, the spondylar dysplasia tended to normalize with age, but mild alterations of the vertebral bodies persisted, even into late childhood. The other radiological manifestations of both patients were identical to those of MDS. CONCLUSION: Our observation suggests that mild spondylar dysplasia may not be uncommon in MDS. PMID- 11214690 TI - Patterson-Lowry rhizomelic dysplasia: a potentially lethal bone dysplasia? AB - We report a Japanese boy, who is considered as having Patterson-Lowry rhizomelic dysplasia, a rare, as yet undefined, skeletal dysplasia. The diagnosis was warranted by the constellation of skeletal abnormalities - mild platyspondyly, hypoplastic ilia, broad proximal femora with prominent lesser trochanters, mild brachymetacarpalia and, most importantly, rhizomelic shortening of the upper limbs with lateral bowing, medial cortical thickening, and medial metaphyseal notching of the humeri. Our patient, unlike previously reported patients, had respiratory distress and died suddenly of unknown cause in late infancy. Our experience may imply the heterogeneity or phenotypic variability of Patterson Lowry rhizomelic dysplasia. PMID- 11214691 TI - CT findings of descending necrotising mediastinitis via the carotid space ('Lincoln Highway'). AB - A 3-year-old girl with fever and neck swelling showed widening of the superior mediastinum on chest radiographs. Contrast-enhanced CT of the neck revealed ill defined low-attenuation areas with a thick, enhanced rim adjacent to the hypertrophied palatine tonsil. The abscess extended inferiorly within the carotid sheath between the carotid artery and the internal jugular vein into the anterior mediastinum. The carotid space is considered an important conduit of descending necrotising mediastinitis and is called the 'Lincoln Highway' as previously suggested. PMID- 11214692 TI - The significance of recurrent lung opacities in neonates on surfactant treatment for respiratory distress syndrome. AB - PURPOSE: To determine the significance of recurrent opacities in chest radiographs of neonates on surfactant therapy for respiratory distress syndrome (RDS) after an initial period of improvement. MATERIALS AND METHODS: Serial pre and post-surfactant chest radiographs on 94 preterm infants with RDS were analyzed and the pattern of chest radiographic response was classified as (a) clear, (b) recurrent opacities, and (c) no response. Their clinical characteristics were also recorded. RESULTS: In 34 infants the RDS changes cleared within 3 days. 31 infants developed lung opacities within 10 days after an initial period of improvement. Twenty-nine infants failed to respond to the surfactant. The corresponding mean birth weights for the three groups were 1.74, 1.19, and 0.76 kg and the mean gestation ages 32.6, 27.7, and 25.4 weeks. The incidence of bronchopulmonary dysplasia (BPD) was highest among the slumping infants (72% vs. 50% in no responders, P<0.001) CONCLUSIONS: The pattern of chest radiographic response is primarily affected by gestation age and birth weight. Recurrent lung opacity after an initial positive response to surfactant therapy may be caused by such factors as edema from barotrauma and patent ductus arteriosus. Infants with intraventricular hemorrhage may demonstrate neurogenic edema. Other contributory factors include pneumonia and abnormal consumption of surfactant. Recurrent lung opacities after surfactant may be a predictor of chronic lung disease in the preterm infant. PMID- 11214693 TI - MRCP in the evaluation of pancreaticobiliary disease in children. AB - BACKGROUND: Radiologic assessment of pancreaticobiliary ductal disease (PBDD) in children currently consists of physiologic tests (radionuclide examinations) or invasive anatomic studies (ERCP and PTC). An accurate noninvasive and reproducible examination that can direct the subsequent need for more invasive studies would be helpful in this patient group. OBJECTIVE: To determine the effectiveness of MRCP as a screening tool for PBBD in the pediatric population. MATERIALS AND METHODS: Over the last year, 33 patients ranging from 7 months to 20 years of age were prospectively evaluated with MRCP on a 1.5 T magnet. One patient was examined twice, several months apart. Thirteen patients had liver transplants. Coronal SPGR and heavily T-2W FSE cross-sectional images were obtained. Standard and oblique 2- to 6-cm-thick slab SSFSE (single-shot fast spin echo) acquisition and 3D MIP reconstruction of 2D FSE images were obtained in the planes of the CBD and pancreatic duct. Nine studies were performed with the patient under sedation with chloral hydrate or nembutal and fentanyl with quiet respiration, and the non-sedated patients were assessed with single breath hold or quiet respiration. Three patients received secretin. MRCP results were correlated with ERCP (9), PTC (7), liver biopsy (13), clinical information (6), surgery (3), and autopsy (2). RESULTS: All 34 studies performed were considered diagnostic. Periportal fluid, proximal bowel fluid, and gallbladder distention did not significantly diminish the diagnostic information in any cases. Motion artifact did not cause serious degradation in image quality. MRCP depicted abnormalities including stones, stricture, intraductal tumor, and extrinsic compression, all of which were confirmed at ERCP, PTC ( two unsuccessful in patients with non-dilated ducts by MRCP), surgery, liver biopsy, and autopsy. There were no false-negative examinations. Normal pancreatic studies performed to exclude pancreas divisum were followed without additional clinical or laboratory evidence of pancreatitis. Secretin administration increased the conspicuity of the pancreatic duct in two of three patients. CONCLUSION: MRCP is a fast non invasive method of evaluating the pancreatic duct and biliary tree in children. A normal MRCP may obviate the need for PTC or ERCP. Abnormalities detected on MRCP can direct the type of intervention. PMID- 11214694 TI - Treatment of oesophageal strictures in children: a comparison of fluoroscopically guided balloon dilatation with surgical bouginage. AB - PURPOSE: To compare the technical feasibility and procedural complications of fluoroscopically guided balloon dilatation with conventional surgical bouginage for the treatment of oesophageal strictures in children. MATERIALS AND METHODS: A retrospective analysis of 125 balloon dilatations in 37 children with oesophageal strictures of varying aetiology. Twenty-four of the 37 children also underwent 88 procedures of surgical bouginage and comparison was made between the methods. RESULTS: Fluoroscopic balloon dilatation had fewer technical failures (0/125 vs. 4/88, P<0.02) and fewer iatrogenic perforations (2/125 vs. 5/88 P = 0.1) than surgical bouginage. CONCLUSION: Fluoroscopically guided balloon dilatation is safer and has fewer technical failures than surgical bouginage and should be considered the first line of treatment for oesophageal strictures in children. PMID- 11214695 TI - The relationship between wine consumption and cardiovascular risk: from epidemiological evidence to biological plausibility. AB - Epidemiological studies have suggested that cardiovascular disease morbidity and mortality can be decreased by moderate alcohol consumption. Several recent studies have also separately assessed the relative risk associated with different types of alcoholic beverages. The evidence obtained strongly suggests, although does not prove, that there is a major beneficial effect from drinking a low moderate amount of wine. A meta-analysis has recently been performed on 19 of these studies, selected on the basis of the availability of specific information on the relative risk associated with wine consumption. The results indicate a negative association of moderate (up to 300 ml per day) wine consumption with the risk of cardiovascular events. Although some cardioprotective effects of alcoholic beverages are probably due to ethanol-induced elevation of HDL cholesterol, lowering of fibrinogen plasma levels and, perhaps, of platelet aggregation, it is reasonable to speculate that the cardiovascular protective effects of wine, observed in French and in other populations, may be attributed in part to the antioxidant, vasorelaxant, and antithrombotic properties of its polyphenolic components. PMID- 11214696 TI - Echo-Doppler evaluation of left ventricular diastolic dysfunction during acute myocardial infarction: methodological, clinical and prognostic implications. AB - Left ventricular (LV) diastolic dysfunction has been reported in the subacute and late phase after myocardial infarction and it is becoming increasingly clear that abnormalities of diastolic function during acute myocardial infarction (AMI) have a major role in affecting the prognosis. However, until recent years the study of patients with diastolic dysfunction has suffered from the substantial difficulties inherent in diagnosing, measuring, quantitating and in following it over time. Moreover, the complexity of events encompassed by diastole, which are often difficult to control in the clinical arena, and the lack of data available to guide therapy, have hampered the widespread application of diastology in the clinical setting of AMI. The advent of Doppler echocardiography and its complementary techniques have provided a bedside tool which yields reliable and useful measures of diastolic performance during AMI, placing such an assessment well within the grasp of every clinical echocardiographic laboratory. Determination of the pattern of LV filling by Doppler echocardiography provides important information about LV diastolic function in AMI patients. Clinical data gathered so far demonstrate that Doppler-derived LV filling, specifically the restrictive filling pattern, is a powerful independent predictor of late LV dilation and, most importantly, of cardiac death in patients with AMI and clearly indicate the need for evaluating and monitoring LV diastolic function in these patients. Large scale studies, utilizing simple and easy to measure Doppler indexes of LV filling are needed to assess the efficacy of medical therapy in patients with acute LV diastolic dysfunction during AMI. PMID- 11214697 TI - Surgical and percutaneous myocardial angiogenesis induction. Part II- neoangiogenesis. AB - Coronary artery bypass surgery and angioplasty provide symptomatic relief in patients with ischemic heart disease, but despite advancement in technique and devices, these methods are not applicable to a subset of patients with angina refractory to medical treatment. Bypass surgery might not be feasible because of lack of suitable conduits, diffuse coronary disease or poor distal run-off, and coronary angioplasty is sometimes not applicable due to chronic total occlusion, diffuse disease or extreme tortuosity. We have previously reviewed the available experience with laser-induced direct myocardial revascularization, one of the new potential treatment modalities for this patient subset. One of the potential mechanisms of action for laser treatment is the induction of neoangiogenesis. In the second part of our article we review the available experience with the induction of myocardial angiogenesis using different growth factors or the genes encoding for them. PMID- 11214698 TI - Spinal cord stimulation in patients with refractory anginal pain and normal coronary arteries. AB - BACKGROUND: Spinal cord stimulation (SCS) has been shown to be effective in patients with refractory angina and coronary artery disease. No previous study assessed the clinical effects of SCS in patients with refractory angina who present angiographically normal coronary arteries. METHODS: SCS was performed in 7 patients (4 men, 3 women, mean age 59.3 +/- 11 years) with refractory angina and normal coronary arteries. Clinical status was assessed 1 month after SCS device implantation and at a mean follow-up of 11 months (range 2-17 months) by: 1) an estimate of the number of anginal attacks and nitrate consumption in the 2 weeks prior to implantation and to follow-up visits; 2) a score of quality of life by a visual analogic scale; 3) a five-item questionnaire assessing effort angina and satisfaction with treatment; 4) treadmill exercise testing. RESULTS: At the last follow-up the number of anginal episodes (p < 0.001) and nitrate consumption (p < 0.004) were both reduced by SCS. Visual analogic scale score improved from 2.1 +/- 0.98 to 9.0 +/- 0.9 (p < 0.001) at 1 month and to 6.4 +/- 2.3 (p < 0.01) at the last follow-up. Questionnaire analysis showed that mild (p = 0.006) and moderate (p = 0.000) physical activity, as well as patient satisfaction with anginal status (p = 0.000) and with current treatment (p = 0.000) all improved by SCS. Finally, time to 1 mm ST segment depression, time to angina, and exercise duration were all prolonged by SCS. CONCLUSIONS: Our data point out that SCS may considerably improve anginal symptoms and exercise tolerance in a significant number of patients with refractory angina and normal coronary arteries and therefore it should be considered as a valuable treatment option in this group of patients. PMID- 11214699 TI - Effect of intermittent subdiastolic pressure in thigh cuffs on human arterial baroreflex. AB - BACKGROUND: We investigated the effects of subdiastolic variations of the pressure inside the thigh cuffs on cardiovascular oscillations and arterial baroreflex sensitivity in humans. METHODS: During 10 min of controlled breathing at low (0.1 Hz) and high (0.25 Hz) frequencies, 30 healthy subjects underwent variations of the pressure inside the thigh cuffs (from 0 to 40 mmHg) at 0.25 and 0.1 Hz respectively; the periods of controlled breathing without cuff pressure modulation were used as a control. The frequency responses of cardiovascular signals were assessed using spectral analysis, and baroreflex sensitivity by the sequence method. RESULTS: Cuff pressure modulation at 0.25 Hz did not affect the RR interval, arterial pressure, or baroreflex sensitivity; at 0.1 Hz it did not change the RR interval and arterial pressure, but engaged (0.76 +/- 0.2 of coherence) and increased the low frequency oscillations of the RR interval (from 5.6 +/- 1 to 6.1 +/- 0.9 ln ms2, p < 0.05) and improved baroreflex sensitivity by 25% (from 14.2 +/- 9 to 17.7 +/- 10 ms/mmHg, p < 0.01). CONCLUSIONS: Subdiastolic thigh cuff pressure modulation at 0.1 Hz improved the low frequency oscillations of heart rate and baroreflex sensitivity. This approach represents a new and simple non-pharmacological strategy for acutely improving baroreflex sensitivity in humans. PMID- 11214700 TI - Prevalence and correlates of syncope-related traumatic injuries in tilt-induced vasovagal syncope. AB - BACKGROUND: Vasovagal syncope represents the most common form of syncope in the general population and is usually considered as a benign affection. However, syncope-related traumatic injuries may represent a major complication of such a condition in a relevant percentage of cases. The aim of this study was to assess the prevalence and clinical correlates of syncope-related trauma in a cohort of consecutive patients with recurrent vasovagal syncope. METHODS: Three hundred and forty-six consecutive patients were studied in whom a diagnosis of vasovagal syncope was established. All subjects were interviewed with a standard questionnaire in order to collect all possible information about their clinical history and the occurrence of trauma during syncopal spells. RESULTS: Ninety-four of the 346 patients (27.2%) reported at least one syncope-related traumatic injury. In 31/346 cases (8.9%) the severity of trauma had determined hospital admission and surgical treatment. When compared to the rest of the study population, patients with syncope-related trauma showed a higher prevalence of male gender (p < 0.01), a higher absolute number (p < 0.01) and frequency (p < 0.01) of syncopal episodes in their history. Patients with trauma also reported a shorter duration of warning symptoms preceding syncope (p < 0.01), while showing a higher prevalence of positive cardioinhibitory response to tilt table testing (p < 0.01). Moreover, the number of syncope-related injuries was found to correlate significantly with the number of syncopal spells (r = 0.64, p < 0.01). CONCLUSIONS: Most practicing physicians consider vasovagal syncope as simply a benign affection in young people. However, such a clinical view should be partially revised, as recurrent vasovagal syncope is associated with significant trauma-related morbidity. PMID- 11214701 TI - Gated blood pool tomography for the evaluation of global and regional left ventricular function in comparison to planar techniques and echocardiography. AB - BACKGROUND: Multigated radionuclide ventriculography (MUGA) is a simple and reliable tool for the assessment of global systolic and diastolic function and in several studies it is still considered a standard for the assessment of left ventricular ejection fraction. However the evaluation of regional wall motion by MUGA is critical due to two-dimensional imaging and its clinical use is progressively declining in favor of echocardiography. Tomographic MUGA (T-MUGA) is not widely adopted in clinical practice. The aim of this study was to compare T-MUGA to planar MUGA (P-MUGA) for the assessment of global ejection fraction and to transthoracic echocardiography for the evaluation of regional wall motion. METHODS: A 16-segment model was adopted for the comparison with echo regional wall motion. For each one of the 16 segments the normal range of T-MUGA ejection fraction was quantified and a normal data file was defined; the average value 2.5 SD was used as the lower threshold to identify abnormal segments. In addition, amplitude images from Fourier analysis were quantified and considered abnormal according to three different thresholds (25, 50 and 75% of the maximum). RESULTS: In a study group of 33 consecutive patients the ejection fraction values of T-MUGA highly correlated with those of P-MUGA (r = 0.93). The regional ejection fraction (according to the normal database) and the amplitude analysis (50% threshold) allowed for the correct identification of 203/226 and 167/226 asynergic segments by echocardiography, and of 269/302 and 244/302 normal segments, respectively. Therefore sensitivity, specificity and overall accuracy to detect regional wall motion abnormalities were 90, 89, 89% and 74, 81, 79% for regional ejection fraction and amplitude analysis, respectively. CONCLUSIONS: T MUGA is a reliable tool for regional wall motion evaluation, well correlated with echocardiography, less subjective and able to provide quantitative data. PMID- 11214703 TI - Healing of acute myocarditis with left ventricular assist device: morphological recovery and evolution to the aspecific features of dilated cardiomyopathy. AB - Dilated cardiomyopathy may result from an acute myocarditis. Little is reported in vivo documenting the progression from the acute inflammatory disease to the healing phase. We describe the consecutive light and electron microscopy studies performed on five myocardial sample series in a 47-year-old female patient who was referred to our hospital with acute myocarditis. She was sustained with left ventricular assist device (LVAD) for 63 days, and then she died of cerebral hemorrhage. The first three consecutive endomyocardial biopsies (days 2, 4, 36 from onset) documented the acute and early healing phase of the inflammatory disease. In the last two biopsies (days 50 and 64 from onset) active inflammation and myocyte necrosis were absent. The histopathological features were those commonly observed in most patients diagnosed with dilated cardiomyopathy, namely myocyte hypertrophy, nuclear size and shape irregularities, and interstitial fibrosis. Overall, the myocyte morphology significantly improved and LVAD support likely contributed to the structural recovery. The major conclusions to be drawn from this case are: 1) the aspecific pathologic findings of dilated cardiomyopathy patients may result from an acute myocardial inflammation; 2) immediate endomyocardial biopsy in patients with clinically diagnosed myocarditis minimizes the risk of missing the diagnosis of inflammatory disease; to this aim a precise definition of "early onset" is especially needed; 3) LVAD support may contribute to the morphological recovery of severely damaged myocytes. PMID- 11214702 TI - Estrogen derivative relaxes rabbit aorta via the endothelial receptor system. AB - BACKGROUND: It is well known that sexual hormones, in particular estrogens, may influence the cardiovascular system. Experimental and clinical studies have shown that estrogen directly or indirectly modulates the reactivity of vascular smooth muscle but at present the mechanism of action of this hormone has yet to be clarified. The aim of this study was to evaluate the vascular effects of a synthetic non-steroid estrogen, diethylstilbestrol, and the possible involvement of endothelial function. METHODS: We investigated, on aortic strips of a female rabbit, the inhibitory effects of diethylstilbestrol on the contractions induced by different spasmogenic agents, noradrenaline (10(-6) M), angiotensin II (10(-6) M), serotonin (10(-6) M), and KCl (10(-1) M). Some experiments were performed in high K+, Ca++-free solution. In some experiments endothelial function was abolished by mechanical ablation. Another series of experiments was incubated (30 min) with N(G)-monomethyl-L-arginine, which inhibits nitric oxide synthase or with tamoxifen, a specific antagonist of estrogen receptors. RESULTS: At doses from 10(-6) M to 10(-4) M, diethylstilbestrol showed an evident spasmolytic action on contractions induced by noradrenaline, angiotensin II and serotonin but no significant effect was observed on KCl spasm. The inhibitory response of diethylstilbestrol to increased vascular tone induced by noradrenaline disappeared when the endothelial function, validated by the acetylcholine test, was abolished by mechanical ablation. When tested in high K+, Ca++-free solution, diethylstilbestrol did not significantly shift the cumulative dose-response curve of calcium. In the experiments performed with N(G)-monomethyl-L-arginine, diethylstilbestrol failed to induce vasodilation suggesting that its action may be related to synthesis of nitric oxide. Moreover, in the presence of tamoxifen, diethylstilbestrol was unable to induce vasodilation. CONCLUSIONS: The early occurrence of vasodilation is in favor of a direct effect and seems to exclude a regulation of gene expression. These results suggest that estrogens may directly regulate vascular tone interacting with its specific endothelial cell receptors through the release of nitric oxide. PMID- 11214704 TI - Dynamic left ventricular outflow tract obstruction: an unusual mechanism mimicking anterior myocardial infarction with cardiogenic shock. AB - Cardiogenic shock is a frequent and threatening complication in the course of acute myocardial infarction. Besides the well known causes (left ventricular failure, acquired interventricular defect, papillary muscle rupture, free wall rupture) other less frequent mechanisms recognize a functional substrate. The recognition of such mechanisms makes us to revert to the treatments with completely different prognostic implications. In our Coronary Care Unit we encountered, in a period of 12 months, 4 patients who presented clinical, electrocardiographic and/or echographic signs and symptoms of acute myocardial infarction, with different degrees of heart failure up to cardiogenic shock. Only 1 patient showed a severe stenosis of the left anterior descending coronary artery and a significant creatine kinase reduction. Left ventriculography, performed at admission, was unable to disclose the true mechanism of clinical presentation. Only a thorough echographic examination disclosed the presence of a dynamic left ventricular outflow tract obstruction as the cause of heart failure culminating in cardiogenic shock. Once recognized, pathophysiological treatment (administration of beta-blockers and withdrawal of vasodilators, inotropic drugs and intra-aortic balloon pump) led to a dramatic improvement, with an almost complete left ventricular function recovery. Left ventricular outflow tract obstruction is a mechanism that can lead to severe heart failure as a complication of an acute myocardial infarction. Conversely such a mechanism can be precipitated by other causes (hypotension, hypovolemia, especially in hypertensive patients) and can mimic an acute myocardial infarction. Its incidence is not negligible: in our Coronary Care Unit it accounted for about 15% of all cases of myocardial infarction requiring inotropic support. An accurate echocardiographic examination is mandatory even after coronary angiography, and always permits the physician to select the appropriate therapy. PMID- 11214705 TI - Images in cardiovascular medicine. Double is better: type IV dual left anterior descending coronary artery and superimposed atherosclerosis. PMID- 11214706 TI - Images in cardiovascular medicine. An unusual case of in-stent restenosis. PMID- 11214707 TI - Development of heart failure in bradycardic sick sinus syndrome. AB - Mounting evidence shows that elevated resting sinus rate is an independent predictor of cardiovascular morbidity and mortality in the general population, in elderly subjects, and in patients with myocardial infarction or hypertension. Therefore, a rather slow sinus rate appears to be a protecting factor acting through several mechanisms. The present contribution focuses on the relationship between sinus rate and heart failure. Its major objectives are to discuss whether in patients with heart failure a rather slow heart rate is advisable and whether a sinus bradycardia secondary to sinus node dysfunction can facilitate the development of heart failure. It has been reported that among patients with left ventricular dysfunction, increased sinus rate was a predictor of cardiovascular death at univariate analysis; however, a multivariate analysis to verify whether sinus rate was an independent predictor of mortality was not performed. Randomized trials carried out by utilizing beta-blockers or amiodarone in patients with heart failure showed that heart rate reduction by these drugs was a marker of their ability to reduce mortality. However, beta-blockers and amiodarone have additional pharmacological effects which interfere with the disease substrate. So, at present, though the results of these trials show that a rather slow sinus rate is advisable, we do not know whether in patients with heart failure sinus rate represents an independent predictor of mortality as in patients with myocardial infarction or hypertension and whether the reduction of sinus rate per se is beneficial. The results of the recent randomized THEOPACE trial showed, for the first time, that in a patient population with symptomatic sinus bradycardia (sinus rate < 50 b/min), an increase in heart rate, induced by DDD pacing or oral theophylline, reduced the incidence of overt heart failure. Therefore, sinus bradycardia seems to play a role in the genesis of heart failure. In a post-hoc analysis of the results of this trial it emerged that in the control (not treated) group, the subjects with sinus bradycardia more prone to develop heart failure were those of old age, about 80 years, with organic heart disease and severe chronotropic incompetence. However, this conclusion needs further validation. PMID- 11214708 TI - Regulation of von willebrand factor of human endothelial cells exposed to laminar flows: an in vitro study. AB - The effect of laminar flow on the regulation of von Willebrand Factor (vWF) of cultured human umbilical vein endothelial cells (HUVECs) was studied. Confluent endothelial monolayers were exposed to shear stresses (0.2 and 1.0 Pa) from 2 to 24 h. vWF was labelled with indirect immunofluorescence method and observed with 3D fluorescence microscopy. The distribution of vWF and the cytoskeleton organization were observed simultaneously by double fluorescence labelling. More actin stress fibers and an increased release of vWF appeared in the cells exposed to flow at the same time. The qualitative and quantitative results showed that there was not only a shear-dependent regulation but also a time-dependent modification. For a short-time shear stimulation, both 0.2 Pa and 1.0 Pa shear stresses induced a release of vWF from the endothelial cells. In contrast, after 24 h exposure to 1.0 Pa shear flow, vWFs were much more in the cells than that in the cells exposed to 0.2 Pa for 24 h (p < 0.01) or that in the control cells (p < 0.05). TNF-alpha caused a decrease of vWF and Weibel-Palade bodies in the cells. PMID- 11214709 TI - Exposure of human erythrocytes to oxygen radicals causes loss of deformability, increased osmotic fragility, lipid peroxidation and protein degradation. AB - The effects of two oxygen radical generating systems (H2O2 and ascorbate/Fe+2) on erythrocyte deformability, osmotic fragility, lipid peroxidation and protein degradation were studied. Incubation of erythrocytes with different concentrations of H202 (5-20 mM) or ascorbate/Fe+2 (10/0.1-40/0.4 mM) caused a loss of deformability and increased osmotic fragility. The loss of deformability has occurred in a dose-dependent fashion and was proportional to the extent of malonyldialdehyde (an indicator of lipid peroxidation) and alanine production (an indicator of protein degradation). Prior exposure of the erythrocytes to carbon monoxide (known to inhibit heme-protein degradation) prevented almost completely the loss in deformability caused by H2O2, indicating that the loss in deformability was due mainly to protein degradation rather than to lipid peroxidation. Erythrocytes incubated with either of the two systems have also shown morphologic changes characterized by a dose-dependent increase in echinocyte formation. The results indicate the importance of oxidatively damaged proteins in compromising the rheologic behaviour of the erythrocytes, particularly when the free radicals are involved. PMID- 11214710 TI - Evaluation of different methods used to measure malonyldialdehyde in human erythrocytes. AB - Malonyldialdehyde (MDA), a secondary product of lipid peroxidation is widely used as an indicator of lipid peroxidation. Eight of the most frequently used methods for measuring MDA have been evaluated with regard to their sensitivity and reproducibility. The sensitivity of these methods for pure MDA solution was in the order: Satoh's > Stocks and Dormandy's >> Buege and Aust's > Dresel's >> Slater's > Yoshioka's et al. > Yagi's > Jain's method. Whereas the sensitivity of the first four methods for erythrocyte MDA was in the order: Stocks and Dormandy's >> Buege and Aust's > Satoh's > Dresel's method. The reproducibility (expressed as coefficient of variation) of these four methods for erythrocyte MDA were: 3.5%, 17.9%, 31.5% and 16.1%, respectively. These results indicate that Stocks and Dormandy's method has the highest sensitivity and an excellent reproducibility for erythrocyte MDA. Also, it was found to be simple and many samples can be treated in a relatively short time. When standard MDA (0.1-15 nmol/ml) was incubated with erythrocytes, the percentage recovery of MDA (using Stocks and Dormandy's method) has ranged from 50-85%. This result indicates that a considerable amount of MDA formed in erythrocytes probably reacts with other cell components and becomes undetectable. Despite this, the determination of MDA level remains a useful indicator of lipid peroxidation and correlates well with the degree of oxidative stress. PMID- 11214711 TI - Validation of a test of the red cell membrane osmotic resistance. AB - The aim of the present work was to validate a new technique for the measurement of resistance of the red blood cell membrane using an automated apparatus called a Fragilimeter. Its principle lies in the measurement of the extinction of a laser beam projected through a red blood cell suspension subjected, by diffusion, to a variation of salinity from an isotonic equilibrium (154 mM NaCl) to, a hypotonic one, 25 mM NaCl. The variation of osmotic pressure induces on the cells a progressive lysis and a modification of the extinction of the transmitted light. The validation of the method was based on the comparison between results obtained with the Fragilimeter and those obtained using the reference DACIE technique. Analyses were based on blood samples from healthy donors. The determination of the initial, the 50% and the full haemolysis thresholds allowed observation of the fragility of the cell, through its membrane resistance. The physical phenomenon measured in these cells when subjected to various ionic strengths is discussed on the basis of observations realised by means of an optical microscope. PMID- 11214713 TI - Influence of neuraminidase on the characteristics of microrheology of red blood cells. AB - Surface charge was removed from RBC (erythrocyte) membrane to different degrees with biochemical methods, i.e., treatment of RBCs with neuraminidase, either using different doses for the same incubation time (1 hour) or using the same dose (75 milli-unit) for different incubation time. Several rheological properties of the RBCs with surface charge removal were observed, including the deformation index DI (using traditional ektacytometry) orientation index (DI)or and small deformation index (Dl)d (using new ektacytometry), the viscosity at low and high shear rates (using a cone-plate rotating viscosimeter). In addition, photographs of RBCs aggregation under a microscope and the histograms of RBC aggregate size after treatment with neuraminidase were obtained. It is found from these experiments that the decrease of the surface charge of RBCs leads to the decrease in the deformation and orientation indices as well as the increase in blood viscosity. PMID- 11214714 TI - Hemorheology in asymptomatic HIV-infected patients. AB - Although cardiac and vascular complications have been recognized among patients infected with the Human Immunodeficiency Virus-1 (HIV-1), their vascular biology and rheology have not been studied. Rheology of red blood cells (RBC) was assessed with an erythroaggregometer in 22 HIV-1 infected asymptomatic patients (pts) and 17 healthy HIV negative controls (C). All participants were normotensive, nondiabetics, had normal lipid levels and had an hematocrit ranging from 37 to 44% and hemoglobin levels > or = 12 g/100 ml. Patients had a shorter RBC aggregation characteristic time than controls (1.49 +/- 0.17 vs. 2.04 +/- 0.41 s, p = 0.001) and an increased disaggregation shear rate (166 +/- 34.9 vs. 122 +/- 25.4 s(-1), p = 0.001). This hyperaggregation tendancy was associated with increased gamma-globulin (18.3 +/- 3.3 vs. 13.7 +/- 1.9 g/l, p = 0.01) and fibrinogen (3.52 +/- 0.57 vs 3.03 +/- 0.48 g/l, p = 0.003) levels and with an increased erythrocyte sedimentation rate (ESR) (25 +/- 14.3 vs. 12.3 +/- 7.5 mm, p = 0.02). Even in patients with ESRs ranging within normal values (< or = 20 mm), the aggregation characteristic time was found lower in patients than in controls (p = 0.004). There was no correlation between these rheological changes and the CD4+ T-cell count. The 17 patients receiving an antiviral therapy had lower CD4+ T-cell counts than their 5 untreated counterparts (244.7 +/- 167 vs. 410 +/- 106/mm3, p = 0.025), and a higher disaggregation shear rate (177.4 +/- 38.2 vs. 127 +/- 25.4, p = 0.01). Thus, an impairment of rheological characteristics is observed in asymptomatic HIV-I infected patients in association with changes in plasma proteins. PMID- 11214712 TI - Importance of measurement temperature in detecting the alterations of red blood cell aggregation and deformability studied by ektacytometry: a study on experimental sepsis in rats. AB - It is well known that RBC rheological parameters are affected by temperature. Usually, the measurement temperature of these parameters is kept constant throughout a given study, however it can be seen that different temperatures are used by different groups, during the measurement of a given parameter. It is assumed that the data should not be qualitatively different when measured at different temperatures, although significant quantitative differences exist. This study revealed that the selected temperature for RBC elongation index measurements by ektacytometry is important in detecting a given impairment in RBC deformability induced by experimental sepsis. RBC elongation indexes were found to be significantly different in septic and normal rats, only if measured at 37 degrees C. The differences in RBC aggregation parameters for septic and normal rats were also affected by the measurement temperature, however statistically significant differences were present in a wider range of temperatures between 25 37 degrees C. Therefore, it is strongly recommended that the measurement of RBC deformability and aggregation be performed using a controlled-temperature device, set to 37 degrees C. PMID- 11214715 TI - High and low molecular weight heparins do not modify red blood cell aggregability in vitro. AB - The usefulness of heparins as anticoagulants has been demonstrated, but their effects on hemorheological parameters, such as erythrocyte aggregability, are under discussion. If the heparins had adverse effect on erythrocyte aggregability, its use would be especially undesirable in patients with pathologies involving red blood cell hyperaggregability as is the case of cardiac disease. In the present study we examine the in vitro effect of unfractionated and fractionated heparins on red blood cell aggregability. The results show that heparins do not increase this rheological parameter but show a slight tendency to lower it. PMID- 11214716 TI - Students with disabilities: a national survey of participation in school activities. AB - INTRODUCTION: The policies of integration and full inclusion in school activities have been enacted to promote the independence and social participation of students with disabilities. This study examined the nature and extent of participation in schools by students with disabilities in the context of the physical, social and psychological features of the school environment. METHOD: A national survey was completed by 1180 teachers of students with disabilities in the US describing student participation in school activities encompassing involvement in social activities, sports, academic and artistic/creative endeavours. RESULTS/CONCLUSIONS: Multivariate analysis revealed that school life in elementary, middle and high school could be defined by six distinct factors describing individual and group roles. Structural equation modelling yielded a second order latent variable that captured the complex and multi-dimensional aspect of participation, accounting for availability, eligibility, student characteristics/status, and student choice within a larger framework of participation. PMID- 11214717 TI - Evaluation of the quality of life in Brazilian women with fibromyalgia, through the medical outcome survey 36 item short-form study. AB - PURPOSE: The purpose of this study is to assess the impact of Fibromyalgia (FM) on the female patient's quality of life who attended the Rheumatology Outpatient Unit of Sorocaba Hospital Complex and compare it to the quality of life of healthy control group, through the Medical Outcome Study Short-form 36 item Survey (SF36). SUBJECTS: 32 women who fitted the American College of Rheumatology Classification Criteria for Fibromyalgia and 28 healthy women. MATERIALS AND METHODS: The groups were submitted to 'Medical Outcome Study 36 Item Short-form Survey' (SF36). This questionnaire is composed of 8 scales about several aspects of the quality of life. RESULTS: The SF36 scales in the Fibromyalgia group presented the following results: general health--43.3; functional ability--39.4; bodily pain--26.5; physical functioning--14.8 (0-75); vitality--38.5 (5-85); emotional functioning--32.2; mental health--44.2; social functioning--45.1. The SF36 scales in the control group presented the following results: general health- 73.2; functional ability--86.6; bodily pain--68.9; physical functioning--82.4; vitality--59.6; emotional functioning--78.5; mental health--67.4; social functioning--77.9. Significant statistics variations in all evaluated scales were presented by the survey group. CONCLUSION: Fibromyalgia has had a negative impact on the quality of life. PMID- 11214718 TI - Development of an ADL instrument targeting elderly persons with age-related macular degeneration. AB - BACKGROUND: In order to estimate the needs of early intervention in a health education program, an ADL instrument measuring feelings of (in)security was needed. The instrument was intended to detect early signs of decline and to evaluate ADL performance among persons with AMD. An evaluative instrument must have a high level of responsiveness, which is the ability to detect true changes over time but must also show a high level of intra-individual agreement in a test retest assessment. PURPOSE: The purpose of this study was to develop an ADL instrument for evaluative purposes and to establish the reliability and the responsiveness of the instrument. METHOD: The target group comprised all persons referred by an ophthalmologist for low vision rehabilitation, 65 years and older, living at home, with aged-related macular degeneration as the primary diagnosis and with distance visual acuity of the better eye with best correction not lower than 0.1. A non-parametric statistical method that is developed for paired ordered parametrical data was applied in order to measure the systematic and occasional intra-rater disagreement separately and to measure the responsiveness. CONCLUSION: The test-retest study showed that the ADL-instrument had a high level of test-retest stability, which is a condition for responsiveness. The instrument was found to be responsive. It could therefore detect true longitudinal changes and be used for evaluative purposes targeting elderly with AMD. PMID- 11214719 TI - Non-traumatic lower limb older amputees: a database survey from a geriatric centre. AB - PURPOSE: The purpose of this survey was to examine the characteristic of a geriatric population admitted for amputation of a lower limb and to explore some of the factors that may affect the course of their hospital stay. METHOD: The study took place in the geriatric division of a tertiary general hospital and included a close geriatric-orthopaedic liaison. Two-hundred and forty-one patients were included in the final analysis. RESULTS: Many above knee amputations were performed, which correlated with advanced age. Rates of in hospital mortality and systemic complications were 16% and 19%, respectively. Thirty-three percent of the patients were discharged back home, and only 6% were supplied with an artificial limb. The general condition of most patients remained poor. CONCLUSION: We conclude that despite a team approach to the care of the geriatric amputee a poor functional result was obtained. By encouraging earlier referrals from the community it is postulated that a reduction in the costly provision of antibiotics would be beneficial and that perhaps lower levels of amputation could be performed thereby enhancing the possibilities for ambulation. PMID- 11214720 TI - An investigation into the predictive ability of rehabilitation clinicians. AB - PURPOSE: There is increasing pressure by providers, purchasers and recipients of service within the United Kingdom for a more accurate prediction of rehabilitation outcomes. The purpose of this research was to investigate how accurately clinicians were predicting rehabilitation outcomes. METHOD: The study was carried out among 47 patients admitted to a general rehabilitation unit. The Functional Independence Measure and Functional Assessment Measure (FAM) were used as the outcome measure. RESULTS: The results showed a statistically significant positive correlation between goal scores and discharge scores as a total population using Spearmans correlation co-efficient. When breaking the sample into an orthopaedic and CVA population, the predictive ability for the orthopaedic population was consistently higher than for the CVA population. CONCLUSIONS: The results of this study suggest that the predictive ability of clinicians is good for the rehabilitation population although the prediction is consistently better with the orthopaedic population than the CVA population. PMID- 11214721 TI - Rehabilitation of a quadruple amputee subsequent to electrical burns sustained whilst hang gliding. AB - PURPOSE: The purpose of this article is to describe the management, difficulties encountered and level of independence achieved during the initial stage of a quadruple amputee's rehabilitation. METHOD: This is a case study of the rehabilitation of the first known person losing all four limbs due to electrocution whilst hang gliding. RESULTS: The patient became a successful upper limb prosthetic user and returned to work six hours a day. Full independence in activities of daily living was not achieved nor considered practical. Independent walking was accomplished in physiotherapy. however an electric wheelchair remains the only functional means of mobility. CONCLUSION: The rehabilitation is described in detail to assist those managing such a rare and complex case. PMID- 11214723 TI - Variation in molecular species of polar lipids from thermoplasma acidophilum depends on growth temperature. AB - Five types of molecular species of C40 isoprenoid chains, having different numbers of cyclopentane rings, were detected in the ether core lipid of Thermoplasma acidophilum. The average cyclization number of the hydrocarbon chains in the lipids increased with increasing growth temperatures. PMID- 11214722 TI - Effect of a low-fat diet enriched with oleic acid on postprandial lipemia in patients with type 2 diabetes mellitus. AB - The aim of the present study was to compare the effects of a low-fat diet enriched with oleic acid to those of a low-fat diet enriched with linoleic acid on fasting lipids, postprandial lipemia, and oxidative susceptibility of low density lipoprotein (LDL) in patients with type 2 diabetes mellitus (DM). In a 3 wk randomized crossover study, eight patients with type 2 DM were given an experimental low-fat diet enriched with either oleic acid or linoleic acid. The oleic-acid-enriched diet contained 5, 15, and 5%, energy from saturated, monounsaturated, and polyunsaturated fatty acids, and the linoleic-acid-enriched diet contained 5, 5, and 15% energy from saturated, monounsaturated, and polyunsaturated fatty acids, respectively. In addition to evaluating the fasting lipids and oxidative susceptibility of LDL, we evaluated postprandial lipemia using an oral fat load at the end of each 3-wk dietary phase. There were no significant differences in fasting lipid profile or lag time of LDL oxidation between the two experimental dietary phases. The average and maximal increments of remnant-like particle (RLP) cholesterol levels during oral fat load were significantly higher after the oleic-acid-enriched dietary phase than after the linoleic-acid-enriched dietary phase. The area under the curve of RLP cholesterol was also significantly larger after the oleic-acid-enriched dietary phase than after the linoleic-acid-enriched dietary phase. These results suggest that the oleic-acid-enriched diet was associated with increased formation of postprandial chylomicron remnants compared with the linoleic-acid-enriched diet. PMID- 11214724 TI - The composition of saturated fatty acids in plasma phospholipids changes in a way to counteract changes in the mean melting point during pregnancy. AB - It has been demonstrated that in pathological conditions with an increase in the calculated mean melting point (MMP) of phospholipid (PL) fatty acids (FA) there are changes in the composition of the saturated FA (SFA), which partially counteract this effect: shorter-chain SFA with lower melting points are increased, while longer-chain less fluid SFA are suppressed. The aim of this study was to determine whether there are differences in MMP during pregnancy and in the newborn and, if so, whether similar adaptive changes occur in the composition of the SFA. The FA composition of plasma PL was determined in healthy women (n = 16) twice during pregnancy (15-24 wk and 29-36 wk) and at delivery and in umbilical venous blood obtained at birth. The MMP of maternal PL was significantly higher at delivery compared to mid-gestation, due to a loss of highly unsaturated FA (HUFA) which were replaced by SFA. In addition, changes in the SFA occurred: 16:0 with lower melting point was higher while 18:0 with higher melting point was lower at delivery. MMP of PL FA in umbilical plasma was lower than in maternal plasma at delivery, which was due to higher HUFA content. In contrast to maternal plasma, 16:0 was lower while 18:0, 20:0, and 24:0 were higher in umbilical plasma resulting in a higher MMP of SFA, tending to raise the overall MMP. It can be concluded that, during pregnancy and in the newborn, the FA composition of SFA changes in a way to counteract changes in MMP induced by reduced and increased HUFA, respectively. PMID- 11214725 TI - Influence of fatty alcohol and other fatty acid derivatives on fatty acid uptake into rat intestinal epithelial cells. AB - We investigated the influence of various substrates on the uptake of long-chain fatty acid into IEC-6, rat intestinal epithelial cell line. The uptake of [3H]oleic acid into IEC-6 cells was a saturable function of the oleic acid concentration. Long-chain fatty acids significantly inhibited the oleic acid uptake into IEC-6 cells and shorter-chain fatty acids had little or no effect. Various fatty acid esters suppressed the oleic acid uptake into IEC-6. Fatty alcohols also inhibited oleic acid uptake into IEC-6 and the length of the carbon chain played an important role. These results suggest that long-chain fatty acid uptake was inhibited by the substrates which had a structure similar to long chain fatty acids, especially those with a long carbon chain. At least two molecules, fatty acid translocase and fatty acid transport protein type 4, which are considered to be involved in the long-chain fatty acid transport into the cell, were expressed on IEC-6 cells, supporting the existence of the carrier mediated system of long-chain fatty acid transport on IEC-6 cells. PMID- 11214726 TI - Modulation of apolipoprotein E-mediated plasma clearance and cell uptake of emulsion particles by cholesteryl ester. AB - Cholesteryl ester, along with triglyceride (TG), is the major core component of plasma lipoproteins. We investigated the effect of core composition on the physical state and metabolic behavior of lipid emulsions, as model particles of lipoproteins. Fluorescence studies using 1,6-diphenylhexatriene analogs showed that although cholesteryl oleate (CO) significantly decreased core mobility, the surface rigidity of phosphatidylcholine (PC) monolayers was independent of core composition. When intravenously injected into rats, the increased amount of core CO tended to retard TG emulsion removal from plasma, and the initial clearance rate was correlated with the amount of apolipoprotein E (apoE) bound from plasma. In addition, PC liposomes with a similar emulsion particle size showed negligible binding of apoE and were cleared at a slower rate compared to all emulsions. Furthermore, the effect of CO on the binding behavior of apoE to the emulsion surface and the emulsion uptake by hepatocytes was assessed in vitro. Replacing core TG with CO was found to decrease the apoE binding capacity to emulsions markedly without changing the binding affinity and thereby to reduce the cell uptake of emulsion particles by HepG2 cells. These results indicate that the physical state of core lipids, which can be modulated by CO content, plays a role in emulsion metabolism through the alteration in apoE binding. PMID- 11214727 TI - In vitro behavior of marine lipid-based liposomes. Influence of pH, temperature, bile salts, and phospholipase A2. AB - To deliver polyunsaturated fatty acids (PUFA) by the oral route, liposomes based on a natural mixture of marine lipids were prepared by filtration and characterized in media that mimic gastrointestinal fluids. First the influence of large pH variations from 1.5-2.5 (stomach) to 7.4 (intestine) at the physiological temperature (37 degrees C) was investigated. Acidification of liposome suspensions induced instantaneous vesicle aggregation, which was partially reversible when the external medium was further neutralized. Simultaneously, complex morphological bilayer rearrangements occurred, leading to the formation of small aggregates. These pH- and temperature-dependent structural changes were interpreted in terms of osmotic shock and lipid chemical alterations, i.e., oxidation and hydrolysis, especially in the first hours of storage. Besides, oxidative stability was closely related to the state of liposome aggregation and the supramolecular organization (vesicles or mixed micelles). The effects of bile salts and phospholipase A2 (PLA2) on the liposome structures were also studied. Membrane solubilization by bile salts was favored by preliminary liposome incubation in acid conditions. PLA2 showed a better activity on liposome structures than on the corresponding mixed lipid-bile salt micelles. As a whole, in spite of slight morphological modifications, vesicle structures were preserved after an acid stress and no lipid oxidation products were detected during the first 5 h of incubation. Thus, marine lipids constituted an attractive material for the development of liposomes as potential oral PUFA supplements. PMID- 11214728 TI - Alpha- and gamma-tocotrienols are metabolized to carboxyethyl-hydroxychroman derivatives and excreted in human urine. AB - Limited information is available regarding metabolism of vitamin E forms, especially the tocotrienols. Carboxyethyl-hydroxychromans (alpha- and gamma-CEHC) are human urinary metabolites of alpha- and gamma-tocopherols, respectively. To evaluate whether tocotrienols are also metabolized and excreted as urinary CEHC, urine was monitored following tocotrienol supplementation. Complete (24 h) urine collections were obtained for 2 d prior to (baseline), the day of, and 2 d after human subjects (n = 6) ingested tocotrienol supplements. The subjects consumed 125 mg gamma-tocotrienyl acetate the first week, then the next week 500 mg; then 125 mg alpha-tocotrienyl acetate was administered the third week, followed by 500 mg the fourth week. Urinary alpha- and gamma-CEHC were measured by high performance liquid chromatography with electrochemical detection. Urinary gamma CEHC levels rose about four- to sixfold in response to the two doses of gamma tocotrienol and then returned to baseline the following day. Significant (P < 0.0001) increases in urinary alpha-CEHC were observed only following ingestion of 500 mg alpha-tocotrienyl acetate. Typically, 1-2% of alpha-tocotrienyl acetates or 4-6% of gamma-tocotrienyl acetates were recovered as their respective urinary CEHC metabolites. A gamma-CEHC excretion time course showed an increase in urinary gamma-CEHC at 6 h and a peak at 9 h following ingestion of 125 mg gamma tocotrienyl acetate. In summary, tocotrienols, like tocopherols, are metabolized to CEHC; however, the quantities excreted in human urine are small in relation to dose size. PMID- 11214729 TI - Mechanisms of dimer and trimer formation from ultraviolet-irradiated alpha tocopherol. AB - Alpha-Tocopherol (alpha-TH) undergoes ultraviolet (UV)-induced photooxidation on the surface of mouse skin to produce a dihydroxydimer, a spirodimer, and trimers as the major products. To study the photochemistry involved, we UV-irradiated alpha-TH in a thin film on a glass petri dish. Photooxidation yielded a mixture of dihydroxydimer, spirodimer, and trimers. In the time-course studies, the dihydroxydimer accumulated and then was further oxidized, whereas the spirodimer and trimers accumulated more gradually. Reaction of two tocopheroxyl radicals forms the dihydroxydimer, whereas the spirodimer may be formed either by photooxidation of alpha-TH to an orthoquinone methide (o-QM) followed by a Diels Alder reaction or by photooxidation of alpha-TH to the dihydroxydimer, followed by two-electron oxidation. Irradiation of a mixture of d10-labeled and unlabeled (d0) dihydroxydimer produced a mixture of labeled and unlabeled spirodimers as detected by positive atmospheric pressure chemical ionization-mass spectrometry. The absence of mixed label spirodimers among products indicated that direct oxidation of the dihydroxydimer is a facile route to the spirodimer and is probably the major spirodimer-forming reaction in alpha-TH photooxidations. Trimer formation from the dihydroxydimer and the spirodimer was observed, however, and requires an o-QM intermediate. Photooxidation of dl0-labeled and unlabeled (d0) dihydroxydimers yielded mixed isotopomers of the trimer products, thus demonstrating that the dihydroxydimer and spirodimers underwent conversion to o-QM intermediates. Photochemical conversion of alpha-TH to UV-absorbing dimer and trimer products may contribute to photoprotection by topically applied alpha TH. PMID- 11214730 TI - Effects of ascorbate on membrane phospholipids and tocopherols of intact erythrocytes during peroxidation by t-butylhydroperoxide: comparison with effects of dithiothreitol. AB - Peroxidation of intact human erythrocytes by t-butylhydroperoxide (tBHP)) was studied. By incubation of the erythrocytes with 1 mM tBHP, reduced glutathione (GSH) was exhausted within 1 min, and tocopherols (Toc) and phospholipids (PL) decreased to nearly their lowest levels (in this study) within 5 min. The rate of decrease of alpha-Toc was faster than that of gamma-Toc, but alpha-Toc was never exhausted. The rates of decrease of Toc were faster than that of PL. Malondialdehyde increased slowly to reach a maximal value at 30 min. Methemoglobin (metHB) reached a maximum at 15 min. The maximal levels of these substances were maintained until 90 min incubation, which indicated that the peroxidation by tBHP had stopped spontaneously until at least 90 min. By the incubation with tBHP for 30 min, phosphatidylethanolamine (PE) and alpha-Toc decreased to about 70 and 30% of control levels, respectively, and gamma-Toc and GSH were almost exhausted. Ascorbate (0.1 mM) afforded protection of 92% to PE, 50% to alpha-Toc, and 65% to gamma-Toc against peroxidation, but ascorbate had no preventive effect at all on the formation of metHB and the decrease of GSH. These results may indicate that ascorbate-mediated protection of the membrane PL against the peroxidation depends primarily on Toc. On the other hand, dithiothreitol (DTT) (5 mM) almost completely prevented the formation of metHB, and DTT completely protected the PL and Toc against peroxidation, indicating the importance of sulfhydryl groups in erythrocytes. PMID- 11214731 TI - Cacao liquor polyphenols reduce oxidative stress without maintaining alpha tocopherol levels in rats fed a vitamin E-deficient diet. AB - The effect of crude polyphenols (CLP) from cacao liquor on vitamin E-deficient rats was examined. The CLP fraction contained 49.8% antioxidative polyphenols such as catechins and their oligomers. Supplementation of the vitamin E-deficient diet with CLP for 7 wk did not prevent the decrease in alpha-tocopherol levels in the liver, kidney, heart, brain, and plasma. The lipid peroxide levels in these tissues increased in the group fed the vitamin E-deficient diet compared with the control group. However, these changes were inhibited in a dose-dependent manner as a result of supplementation of the vitamin E-deficient diet with 0.25, 0.5, or 1.0% CLP. The lipid peroxide levels in plasma increased in the group fed the vitamin E-deficient diet. This change tended to be suppressed as a result of supplementation of the diet with CLP, but the difference was not significant. There was no evidence of absorption and distribution of CLP to the tissues; however, CLP intake resulted in a decrease in oxidative stress without maintaining vitamin E levels in the plasma and the tissues. PMID- 11214732 TI - A long-term seal- and cod-liver-oil supplementation in hypercholesterolemic subjects. AB - In this long-term study, we wanted to explore the effect of dietary supplementation of seal oil (SO) as compared cod-liver oil (CLO) on subjects with moderate hypercholesterolemia. The test parameters included fatty acid composition in serum, blood lipids, platelet aggregation, and the activity of blood monocytes. After a run-in period of 6 mon, 120 clinically healthy hypercholesterolemic (7.0-9.5 mmol/L; 270-366 mg/dL) subjects were randomly selected to consume either 15 mL of SO or CLO daily for 14 mon followed by a 4 mon wash-out period. A third group was not given any dietary supplement (control). Consumption of marine oils (SO and CLO) changed the fatty acid composition of serum significantly. Maximal levels were achieved after 10 mon. No further changes were seen after 14 mon. A wash-out period of 4 mon hardly altered the level of n-3 fatty acids in serum. Addition of SO gave 30% higher level of eicosapentaenoic acid, as compared to CLO. Subjects taking SO or CLO had lower whole-blood platelet aggregation than the control group. Neither SO nor CLO had any effects on the levels of serum total cholesterol, high-density lipoprotein cholesterol, postprandial triacylglycerol, apolipoproteins Al and B100, lipoprotein (a), monocyte function expressed as monocyte-derived tissue factor expression, and tumor necrosis factor. PMID- 11214734 TI - Biosynthesis of eicosapentaenoic acid in the sea urchin Psammechinus miliaris. AB - The sea urchin Psammechinus miliaris (Gmelin) (Echinodermata: Echinoidea) was shown by using a deuterated tracer (D5-18:3n-3) and quantitation by negative chemical ionization gas chromatography-mass spectrometry to convert 18:3n-3 to 20:5n-3. The rate of conversion was very slow, corresponding to 0.09 microg/g tissue/mg 18:3n-3 eaten over 14 d. Deuterated arachidonic acid (D8-20:4n-6) was also included in the diet to give a measure of the relative amounts of diet eaten by the different animals. The recovery of this fatty acid in tissue lipids was 33.7% compared with only 0.95% recovery of D5-18:3n-3 and its anabolites, indicating that the majority of the D5-tracer was catabolized. Considerable elongation of D5-18:3n-3 into 20:3n-3 and a trace of 22:3n-3 was found, and these were accompanied by minor amounts of the intermediates 18:4n-3 and 20:4n-3. No deuterated 22:6n-3 was found. PMID- 11214733 TI - Removal of fat from cow's milk decreases the vitamin E contents of the resulting dairy products. AB - The present study was undertaken to determine whether decreases in fat contents result in lower vitamin E contents. Milk samples of varying fat contents (half and half, whole milk, reduced-fat milk, low-fat milk, and nonfat milk) were obtained from a local dairy on six different occasions. alpha-Tocopherol was the major form of vitamin E (>85%); gamma-tocopherol and alpha-tocotrienol were present to a lesser extent. As the fat contents of milk products decreased from 11 to 0.3%, the vitamin E contents decreased. For example, raw milk as compared to nonfat milk had both higher (-tocopherol contents (45.5 +/- 4.6 vs. 4.5 +/- 0.5 microg/100 g; P < or = 0.0001) and higher total lipids (3.46 +/- 0.49 vs. 0.30 +/- 0.07 g/100 g; P < or = 0.0001). Vitamin E, cholesterol, and total lipids increased as cream was added back to nonfat milk during production. For every 1 mg cholesterol increase, there was an increase of approximately 4 microg of alpha tocopherol; for every 1 g total lipids increase, the alpha-tocopherol content increased by 17 microg. These data demonstrate that removal of milk fat markedly decreases the vitamin E content of various milk products. PMID- 11214735 TI - The first naturally occurring alpha-methoxylated branched-chain fatty acids from the phospholipids of Amphimedon complanata. AB - The phospholipid fatty acid composition of the sponge Amphimedon complanata was reinvestigated, and the 2-methoxy-13-methyltetradecanoic acid, 2-methoxy-14 methylpentadecanoic acid, and 2-methoxy-13-methylpentadecanoic acid were identified for the first time in nature. Structure characterization was accomplished by means of gas chromatographic retention times and gas chromatography-mass spectrometry. These acids could have originated from bacteria in symbiosis with the sponge. PMID- 11214736 TI - A fast and reliable spectroscopic method for the determination of membrane--water partition coefficients of organic compounds. AB - Partition coefficients (Kp) between egg yolk phosphatidylcholine multilamellar vesicles and water were determined for two nonsteroidal anti-inflammatory drugs (indomethacin and acemetacin) using two independent methodologies: derivative spectrophotometry and variation of the experimental acidity constant in the presence of increasing vesicle concentration. Second-derivative spectrophotometry allowed for total elimination of background signal effects arising from lipid vesicles, without the need for separation techniques that may disturb equilibrium states. By using a model based on a simple partition, the values of K(T)p can be obtained directly; furthermore, by performing determinations at two different pH values it is possible to calculate partition coefficients for the neutral and negatively charged forms of the drugs (K(AH)p and K(A)p). In the other methodology, values of apparent acidity constants (K(app)) were determined by spectrophotometry at different pH values and different lipid concentrations, and an increase in K(app) with decreasing lipid concentration was observed for both drugs, and from this dependence it was possible to calculate K(AH)p and K(A-)p for each drug. These values were used as a check for those obtained by derivative spectroscopy, which has proven to be a reliable and more expeditious method to obtain K(AH)p and K(A-)p . PMID- 11214737 TI - A novel assay method for glycosphingolipid deacylase by enzyme-linked immunochemical detection of lysoglycosphingolipid. AB - Lysoglycosphingolipids consist of a sphingoid long-chain base and monosaccharide or complex sugar, and they lack the fatty acyl group present in native glycosphingolipids. Less than 1 pmol of lyso-Forssman glycolipid and lysoganglioside GM1 were detected on a thin-layer chromatogram by an enzyme linked immunochemical coloration method with anti-Forssman glycolipid antibody (FOM-1) and cholera toxin B subunit, respectively. Each spot between 1 and 100 pmol lyso-Forssman glycolipid was immunostained as densely as that of the same amount of native Forssman glycolipid. The density of the lyso-Forssman glycolipid spots increased proportionally with increment in the amount of lysoglycolipid. The density of spots of 0.2-100 pmol lysoganglioside GM1 was also proportional to the amount of each lyso-GM1 spot. These results indicated that less than 1 to 100 pmol of deacylated glycosphingolipid was quantifiable by the immunochemical coloration method with sugar chain-specific antibodies. Glycosphingolipid deacylase, which cleaved an amide bond between the sphingoid long-chain base and fatty acyl chain in ceramide of glycosphingolipid, was assayed by detecting the lyso-Forssman glycolipid produced. Lipophilic compounds, recovered from an aliquot of the reaction mixture of Forssman glycolipid and crude enzyme at appropriate times, were analyzed by thin-layer chromatography. It was found that lyso-Forssman glycolipid was produced in the first 1-2 h by the enzyme and production increased with incubation time. This coloration method is more sensitive and specific than the visualization method with a nonspecific reagent such as orcinol-sulfuric acid reagent. PMID- 11214738 TI - End organ protection by calcium-channel blockers. AB - In recent years, much attention has been given to end organ protection by antihypertensive, anti-heart failure, and anti-ischemic medications. This review describes the available information on end organ protection by calcium-channel blockers (CCBs). In normotensive patients and patients with hypertension treated with long-acting dihydropyridines, medial thickness was thinner than in patients treated with atenolol or in untreated hypertensive patients. Long-term treatment was associated with significant reduction in left ventricular mass. Calcium channel blockers also improved endothelial-dependent relaxation and reversed the vasoconstrictive response to nitric oxide inhibitors. In diabetic patients, CCBs were effective in preserving kidney function and microalbuminurea. The combination of angiotensin-converting enzyme (ACE) inhibitors and CCBs was more effective than ACE inhibitors alone in preserving kidney function. In animal experiments, CCBs prevented development of coronary atheroschlerosis; however, in humans only limited data are available on their antiatherogenic effect. Some studies suggest that CCBs exert antiplatelets properties and may therefore be beneficial in patients with coronary artery disease. PMID- 11214739 TI - Prognosis following acute myocardial infarction in patients with ST-T abnormalities on electrocardiograms obtained before myocardial infarction. AB - BACKGROUND: Many studies have examined the relationship between prognosis after myocardial infarction (MI) and electrocardiographic (ECG) findings at the time of or after the onset of MI. However, little work has been done concerning the association between ECG findings obtained before the onset of MI (pre-MI) and the prognosis after MI. HYPOTHESIS: The study was undertaken to determine whether ST T segment and T-wave morphology on pre-MI ECGs provides useful information for prognosis after acute MI. METHODS: Pre-MI ECGs of 212 patients recorded within the 6-month period before MI were studied for the presence of high-voltage R waves, ST-segment depression, and negative T waves. The Kaplan-Meier method and multivariate analysis were used to determine the relationship between these ECG findings and in-hospital cardiac death. RESULTS: In-hospital cardiac death occurred in 32 (15.1%) patients. The in-hospital mortality rate was 38.5% (5/13) for the patients with high-voltage R waves, 54.5% (6/11) for patients with ST segment depression, and 45.6% (15/33) for patients with negative T waves. The in hospital mortality rate was 13.6% (27/199) for patients without high-voltage R waves, 12.9% (26/201) for patients without ST-segment depression, and 9.5% (17/179) for those without negative T waves. Multivariate analysis identified age and negative T waves as independent risk factors for cardiac death, with a hazard ratio for negative T waves of 3.1. CONCLUSION: Negative T waves on pre-MI ECGs represent an independent predictor of in-hospital cardiac death in patients with MI. PMID- 11214740 TI - Intervention to improve adherence to ACC/AHA recommended adjunctive medications for the management of patients with an acute myocardial infarction. AB - BACKGROUND: The most recent published guidelines regarding management of patients surviving an acute myocardial infarction (AMI) advocate the administration of aspirin (ASA), beta blockers (BB), and angiotensin-converting enzyme inhibitors (ACEi) and discourages the use of calcium-channel blockers (CCB). Previous data collected in our region from the National Registry (NR) showed a dismal compliance with these guidelines. In an attempt to increase physician awareness and to optimize implementation of recommended guidelines, a cardiac and pharmacy steering committee was created. METHODS: The pharmacist assigned to the project identified all patients admitted with an AMI using troponin-I and creatine kinase MB (CK-MB) reports. The pharmacist then contacted physicians to make recommendations if an adjunctive medication was not prescribed for a patient with no apparent contraindications. Administration rates for ASA, BB, ACEi, and CCB were then assessed and compared with the previously obtained baseline data from the NR. RESULTS: At admission, the use of ASA increased from 70 to 72%, BB from 45 to 72%, and ACEi from 12 to 44%. In terms of medications at discharge, ASA use increased from 74 to 88%, BB from 55 to 76%, and ACEi from 30 to 40%. In addition, the prescription rates for CCB at discharge decreased from 36 to 21%. CONCLUSIONS: An interdisciplinary approach for disease management is an effective method for improving adherence to treatment guidelines simply with pharmacy intervention. The percentage of patients receiving the recommended adjunctive medications increased significantly. We propose that these guidelines should be periodically inserviced to physicians. Furthermore, patient counseling sessions should also be instituted to help reinforce the importance of compliance with the medications after discharge, as well as lipid management and smoking cessation. PMID- 11214741 TI - Reduced incidence of clinical restenosis with newer generation stents, stent oversizing, and high-pressure deployment: single-operator experience. AB - BACKGROUND: Over the last 4 years, several newer generation stents have become available, promising to change the scenery of coronary angioplasty (PTCA) with its attendant restenosis rate. HYPOTHESIS: The aim of this study was to review prospectively the results of a single operator adopting a uniform approach with approximately 0.5 mm stent oversizing and high-pressure (> or = 12-16 bar) deployment and compare them with conventional PTCA in a series of 244 consecutive patients. METHODS: The study included 203 men and 41 women, aged 59 +/- 11 years, who presented with stable angina and/or positive exercise testing (n = 75), unstable angina (n = 161), or acute myocardial infarction (n = 8). Dilated vessels included the left anterior descending artery (n = 139), the right coronary artery (n = 86), the left circumflex artery (n = 47), the ramus branch (n = 4), or venous grafts (n = 2). Stents were implanted for dissection, suboptimal PTCA result, and electively. Two groups were compared: 83 patients who underwent balloon PTCA alone and 161 patients who also received stent(s). RESULTS: The two groups had similar demographics, age (58 +/- 10 vs. 59 +/- 11 years), initial vessel stenosis (92 +/- 7 vs. 93 +/- 6%), and left ventricular ejection fraction (51 +/- 9 vs. 51 +/- 8%). Procedural success was also similar (97.6 vs. 99.4%), but as expected the residual stenosis was much lower in the stent group (< or = 0 vs. 17%). The following stents were employed: J & J (n = 1), NIR (n = 117), ACS (n = 59), AVE (n = 9), Inflow GoldFlex (n = 9), Crossflex (n = 5), Wictor (n = 1), Jostent (n = 16), R stent (n = 9), Seaquence (n = 2) and Wallstent (n = 1). Single stents were used in 118 patients, two stents in 31 patients, three in 6 patients, and four in 6 patients. There was one in-hospital death at 3 days unrelated to the procedure. There were no events of subacute stent thrombosis; all patients in the stent group received combined therapy with aspirin and ticlopidine, the latter for 1 month. During 18 +/- 14 months, the clinical restenosis rate was significantly lower in the stent group (6.9%) than in the PTCA group (28.4%) (p = 0.001). CONCLUSION: In a series of 244 consecutive patients, newer generation stents and a consistent approach of stent oversizing and high-pressure stent deployment by a single operator resulted in high procedural success (99%), lack of stent thrombosis (0%), and a very low clinical restenosis rate (7%). PMID- 11214742 TI - Angioplasty decreases prolonged QT dispersion in patients with angina pectoris but not in patients with prior myocardial infarction. AB - BACKGROUND AND HYPOTHESIS: Prolonged QT dispersion (QTd) is shortened by successful percutaneous transluminal coronary angioplasty (PTCA) in patients with ischemic heart disease. Particularly, QTd plays an important role in the prognostication in patients with prior myocardial infarction (MI). However, whether the effect of PTCA on QTd differs in patients with and without prior MI is not clear, and this study sought to clarify this question. METHODS: In 41 consecutive patients with ischemic heart disease, we measured QTd from a routine 12-lead electrocardiogram taken at 72 h before and after successful PTCA. Patients were divided into two groups based on the presence or absence of prior MI: Group 1 consisted of 24 patients with angina (61 +/- 11 years old) without prior MI and Group 2 was comprised of 17 patients (69 +/- 10 years old) with prior MI. QTd was calculated as the difference between the maximum and minimum QT and QT corrected for heart rate (QTc), using Bazett's formula for calculating QTcd. All measurements were obtained manually and blindly. RESULTS: In Group 1, 15 of 24 patients (63%) demonstrated multivessel disease and 16 of 24 (67%) patients had high QTd > 60 ms. Percutaneous transluminal coronary angioplasty decreased QTd and QTcd in Group 1 (QTd, from 83 +/- 35 to 57 +/- 19 ms, p < 0.05 ; QTcd, from 89 +/- 37 to 63 +/- 33 ms, p < 0.05), whereas no changes were observed in Group 2 (QTd, from 73 +/- 25 to 69 +/- 22 ms, NS; QTcd, from 80 +/- 30 to 79 +/- 28 ms, NS). QTd is more sensitive to decrease by successful PTCA in patients with angina than in patients with prior MI. CONCLUSIONS: The effect of successful PTCA on inhomogeneity of ventricular repolarization reflected by QTd in patients with prior MI is different from that in patients without prior MI. PMID- 11214744 TI - Accelerated dobutamine stress testing: safety and feasibility in patients with known or suspected coronary artery disease. AB - BACKGROUND: Dobutamine pharmodynamics require approximately 10 min to reach steady state. Despite this, standard dobutamine stress echo typically uses 3-min stages of advancing dobutamine doses because of safety concerns. HYPOTHESIS: In patients with a high pretest probability of coronary artery disease (CAD), a continuous infusion of high-dose dobutamine is a feasible and safe method for performing a dobutamine stress test. METHODS: Forty-seven consecutive patients (mean age 64 +/- 11 years) with 3.0 +/- 1.4 cardiac risk factors underwent dobutamine stress testing utilizing a single, high-dose (40 mcg/kg/min), continuous dobutamine infusion. The 40 mcg/kg/min infusion was continued for up to 10 min or until a test endpoint had been reached. If a test endpoint was not achieved, atropine (up to 1.0 mg) was added. RESULTS: Heart rate rose from 71 +/- 12 to 137 +/- 18 beats/min at peak (p<0.0001) with a concomitant change in systolic blood pressure (143 +/- 35 vs. 167 +/- 38 mmHg; p = 0.001) but no change in diastolic blood pressure (74 +/- 19 vs. 75 +/- 18 mmHg; p = NS). Target heart rate was achieved in 20 of 47 (43%) patients with accelerated dobutamine alone and in 34 of 47 (72%) with the addition of atropine. An average of 11.6 +/- 3.7 min was required to obtain target heart rate. Subjective sensations from the dobutamine occurred in 49% of patients (palpitations 21%, nausea 6%, chest pain 6%, headache 6%, dizziness 13%), mild arrhythmia in 48% of patients (ventricular premature beats 38%, supraventricular tachycardia 10%), and one patient had nonsustained ventricular tachycardia. CONCLUSION: A single, high-dose (40 mcg/kg/min) dobutamine-atropine protocol provides an efficient means of performing dobutamine stress echocardiography with a similar symptom profile as conventional dobutamine infusion protocols in patients with a high pretest probability of CAD. Randomized, controlled studies will be necessary to assess the sensitivity and specificity of this accelerated dobutamine echo protocol. PMID- 11214743 TI - Clinical characteristics of acute pulmonary thromboembolism in Japan: results of a multicenter registry in the Japanese Society of Pulmonary Embolism Research. AB - BACKGROUND: Although the incidence of acute pulmonary thromboembolism (APTE) has been increasing in Japan, patient characteristics, management strategies, and outcome have not yet been assessed in large series. HYPOTHESIS: The present study was designed to investigate the current status of APTE in Japan. METHODS: Of a total of 533 registry patients with pulmonary thromboembolism, 309 with APTE were analyzed with respect to clinical symptoms and signs, predisposing factors, diagnostic procedures, estimation of deep venous thrombosis, treatment, and clinical course. RESULTS: Main risk factors were recent major surgery, cancer, prolonged immobilization, and obesity; only a few patients had coagulopathy and 36% were in cardiogenic shock at presentation. The majority of registry patients underwent lung scans or pulmonary angiography; 30% were diagnosed only by lung scanning. Venous ultrasonography was used in only 34 patients, while 188 patients underwent at least one diagnostic procedure for deep venous thrombosis. Thrombolysis was more frequently performed in patients with cardiogenic shock, and only a few patients received thromboembolectomy. In-hospital mortality rate was 14%. In patients with cardiogenic shock, the mortality rate was reduced by thrombolysis. The predictors of in-hospital mortality were male gender, cardiogenic shock, cancer, and prolonged immobilization. CONCLUSIONS: The patients in this registry had almost the same findings as those in Western patients, except for some points that had the possibility of demonstrating a difference between Westerners and Japanese in the development of APTE. These results can prove especially helpful in planning prospective, randomized trials that will clarify the impact of widely used treatment modalities on the outcome of patients with APTE. PMID- 11214745 TI - Sleep-Disordered breathing in patients referred for angina evaluation- association with left ventricular dysfunction. AB - BACKGROUND: Clinical observations have linked sleep-disordered breathing to cardiovascular morbidity and mortality, and especially to coronary artery disease. HYPOTHESIS: The study was undertaken to determine the prevalence of sleep-disordered breathing in consecutive patients referred for angina evaluation, and analyzed the parameters influencing the severity of sleep disordered breathing. METHODS: In all, 68 consecutive patients (53 men, 15 women, aged 63.4 +/- 10.0 years) referred for angina evaluation were studied. Coronary angiography, selective left ventriculography, and a polygraphic study with a validated six-channel monitoring device were performed. Full-night polysomnography was used to reevaluate patients with an apnea/hypopnea index > or = 10/h. RESULTS: Sleep-disordered breathing as defined by an apnea/hypopnea index > or = 10/h was found in 30.9% of patients; its prevalence was not increased in patients with and without coronary artery disease (26.5 vs. 42.1%). Multiple stepwise linear regression analysis revealed that the severity of sleep disordered breathing was significantly and independently associated with left ventricular ejection fraction (r = -0.38; p = 0.002), but not with age, body mass index, gender, diabetes mellitus, hypertension, hyperuricemia, hypercholesterolemia, smoking habits, or coronary artery disease. In this group of patients, multiple logistic regression analysis could not demonstrate sleep disordered breathing to be an independent predictor of coronary artery disease. CONCLUSIONS: Sleep-disordered breathing is common in patients referred for angina evaluation. The degree of sleep-disordered breathing is mainly determined by the extent of left ventricular dysfunction. PMID- 11214746 TI - Effects of stent coating on platelets and endothelial cells after intracoronary stent implantation. AB - BACKGROUND: Adhesion molecules are known to be important in the regulation of endothelial cell and platelet functions. Increased platelets P-selectin expression is a marker of stent thrombosis after uncoated stent placement. HYPOTHESIS: The aim of this study was to compare the effects of intracoronary placement of phosphorylcholine (PC)-coated, versus heparin-coated, versus uncoated stents on platelets and endothelial activity. METHODS: Thirty patients (age 55 +/- 10, 27 men) with significant proximal left anterior descending coronary artery stenoses were randomized to elective implantation of PC-coated, versus heparin-coated, versus uncoated stents. Following stent placement, intravenous heparin and aspirin plus ticlopidine were administered. Venous plasma soluble E-selectin, sP-selectin, and intercellular adhesion molecule-l levels were measured before the procedure and 24 and 48 h thereafter as markers of platelet and endothelial cell activation. Patients were excluded if they had a disease known to influence platelet and endothelial cell function. RESULTS: Plasma sP-selectin levels decreased significantly after implantation of PC- and heparin-coated stents (p = 0.04), but remained unchanged in patients randomized to uncoated stents. Plasma sE-selectin levels increased significantly after uncoated stent placement (p = 0.04) and remained unchanged after coated stent implantation. CONCLUSION: In patients treated with combined antiplatelet therapy, implantation of PC- and heparin-coated stents decreased platelet activity without activating endothelial cells, whereas placement of uncoated stents led to endothelial activation without changing platelet activity. These results suggest that PC-coated and heparin-coated stents may be advantageous in limiting thrombotic complications. PMID- 11214747 TI - Electrocardiographic changes of acute cervical spinal cord trauma. PMID- 11214748 TI - Native aortic valve tissue systemic embolization complicating bacterial endocarditis. AB - Systemic embolic events are known complications of bacterial endocarditis. Embolization of prosthetic valves has previously been reported in the literature. We report a case of embolization of native aortic valve tissue to the popliteal artery as the presenting event in a patient with subacute bacterial endocarditis. To our knowledge, this rare complication has not been previously reported. PMID- 11214749 TI - Profiles in cardiology. Sir Leonard Erskine Hill. PMID- 11214750 TI - Determining prognosis after acute myocardial infarction. PMID- 11214751 TI - Peptide and protein PEGylation: a review of problems and solutions. AB - The paper discusses general problems in using PEG for conjugation to high or low molecular weight molecules. Methods of binding PEG to different functional groups in macromolecules is reported together with their eventual limitations. Problems encountered in conjugation, such as the evaluation of the number of PEG chains bound, the localisation of the site of conjugation in polypeptides and the procedure to direct PEGylation to the desired site in the molecule are discussed. Finally, the paper reports on more specific methods regarding reversible PEGylation, cross-linking reagents with PEG arms, PEG for enzyme solubilization in organic solvent and new polymers as alternative to PEG. PMID- 11214752 TI - Nuclear magnetic imaging of an osmotic water uptake and delivery process. AB - The water absorption of NH4F-doped silicone cylinders was studied by spin-echo Fourier nuclear magnetic resonance imaging, in conjunction with gravimetric (mass uptake) and ionic concentration (release of NH4F) measurements. The addition of NH4F greatly increases the water uptake as the inclusions are surrounded by droplets of water when wetted by water diffusing in the polymer. These droplets then expand due to the osmotic pressure difference between the internal droplet and external solution; this expansion is opposed by an elastic restraining force. The rate of ingress into the polymer will depend on the relative chemical potential of water associated with the polymer and the droplet, as well as the diffusion coefficient. Later stages of the absorption process are dominated by the droplets. The dilution of the droplets (from water diffusing into the droplets) slowly reduces the chemical potential driving the process. Hence, the later stages occur without any notable concentration gradient but a slight chemical potential gradient. If the droplet expansion exceeds that which can be restrained by the material, failure around the droplet occurs resulting in the release of the salt and the solution within the droplet. PMID- 11214753 TI - Human preadipocytes seeded on freeze-dried collagen scaffolds investigated in vitro and in vivo. AB - Currently, there is no adequate implant material for the correction of soft tissue defects such as after extensive deep burns, after tumor resection and in hereditary and congenital defects (e.g. Romberg's disease, Poland syndrome). The autologous transplantation of mature adipose tissue has poor results. In this study human preadipocytes of young adults were isolated and cultured. 10(6) preadipocytes were seeded onto collagen sponges with uniform 40 microm pore size and regular lamellar structure and implanted into immunodeficient mice. Collagen sponges without preadipocytes were used in the controls. Macroscopical impression, weight, thickness, histology, immunohistochemistry (scaffold structure, cellularity, penetration depth of the seeded cells) and ultrastructure were assessed after 24 h in vitro and after explantation at 3 and 8 weeks. Preadipocytes penetrated the scaffolds 24 h after seeding at a depth of 299+/-55 microm before implantation. Macroscopically after 3 and 8 weeks in vivo layers of adipose tissue accompanied by new vessels were found on all preadipocyte/collagen grafts. The control grafts appeared unchanged without vessel ingrowth. There was a significant weight loss of all grafts between 24 h in vitro and 3 weeks in vivo (p < 0.05), whereas there was only a slight weight reduction from week 3 to 8. The thickness decreased in the first 3 weeks (p < 0.05) in all grafts. The preadipocyte/collagen grafts were thinner but had a higher weight than the controls at this point in time. The histology showed adipose tissue and a rich vascularisation adherent to the scaffolds under a capsule. The control sponges contained only few cells and a capsule but no adipose tissue. Human-vimentin positive cells were found in all preadipocyte/collagen grafts but not in the controls, penetrating 1188+/-498 microm (3 weeks) and 1433+/-685 microm (8 weeks). Ultrastructural analysis showed complete in vivo differentiation of viable adipocytes in the sponge seeded with preadipocytes. Formation of extracellular matrix was more pronounced in the preadipocyte/collagen grafts. The transplantation of isolated and cultured preadipocytes within a standardised collagen matrix resulted in well-vascularised adipose-like tissue. It is assumed that a pore size greater than 40 microm is required, as preadipocytes enlarge during differentiation due to incorporation of lipids. PMID- 11214754 TI - Tethered-TGF-beta increases extracellular matrix production of vascular smooth muscle cells. AB - Biomaterials developed for tissue engineering and wound healing applications need to support robust cell adhesion, yet also need to be replaced by new tissue synthesized by those cells. In order to maintain mechanical integrity of the tissue, the cells must generate sufficient extracellular matrix before the scaffold is degraded. We have previously shown that materials containing cell adhesive ligands to promote or improve cell adhesion can decrease extracellular matrix production (Mann et al., Modification of surfaces with cell adhesion peptides alters extracellular matrix deposition. Biomaterials 1999;20:2281-6). Such decreased matrix production by cells in tissue engineering scaffolds may result in tissue failure. However, we have found that TGF-beta1 can be used in scaffolds to dramatically increase matrix production. Matrix production by vascular smooth muscle cells grown on adhesive ligand-modified glass surfaces and in PEG hydrogels containing covalently bound adhesive ligands was increased in the presence of 0.04 pmol/ml (1 ng/ml) TGF-beta1. TGF-beta1 can counteract the effect of these adhesive ligands on matrix production; matrix production could be increased even above that observed in the absence of adhesive peptides. Further, TGF-beta1 covalently immobilized to PEG retained its ability to increase matrix production. Tethering TGF-beta1 to the polymer scaffold resulted in a significant increase in matrix production over the same amount of soluble TGF-beta1. PMID- 11214755 TI - Synthetic polymers alter the structure of cervical mucus. AB - Mucosal sites have an innate defense system--which includes immune cells, antibodies, and mucus--to protect the body from opportunistic pathogens. Some sexually transmitted diseases (STDs), such as HIV, utilize host defense mechanisms to evade detection by infecting motile immune cells present at the site. The infected cells migrate through the mucus layer and penetrate the epithelium undetected. A new strategy for preventing STDs could involve inhibiting cell migration through the mucus. One method for inhibiting migration is to alter the barrier property of mucus by modifying its gel structure. Mucin, the structural component of mucus, is a high molecular weight anionic molecule, which forms an entangled fiber network through non-covalent interactions. The addition of nonionic or cationic polymers, such as poly(ethylene glycol) (PEG) or poly(vinyl pyridine) (PVP), altered the overall gel structure as revealed by scanning electron microscopy (SEM), while anionic poly(acrylic acid) had little effect on the structure. Acid residues on mucin associate with PEG through hydrogen bonds to form regions of coalesced fibers within the mucus. PVP, however, interacts with mucin via electrostatic bonds, forming a gel that had areas of aggregated fibers adjacent to regions with virtually no fibers. These results suggest that addition of small amounts of certain synthetic polymers will modify mucus structure; these changes should alter the barrier properties of mucus. PMID- 11214756 TI - Triggered release of calcium from lipid vesicles: a bioinspired strategy for rapid gelation of polysaccharide and protein hydrogels. AB - The bioinspired strategy of triggered release of Ca2+ from liposomal compartments was used to induce rapid gelation of polysaccharide and protein-based hydrogels. Thermally triggerable liposomes were designed by entrapping CaCl2 within liposomes constructed of 90% dipalmitoylphosphatidylcholine and 10% dimyristoylphosphatidylcholine. These liposomes released greater than 90% of entrapped Ca2+ when heated to 37 degrees C. A precursor fluid containing liposomes suspended in aqueous sodium alginate remained fluid for several days at room temperature but gelled rapidly when heated to 37 degrees C, as a result of Ca2+ release and formation of crosslinked Ca-alginate. Alternatively, thermally triggered Ca2+ release from liposomes was used to activate enzyme-catalyzed crosslinking of proteins to form hydrogels. A mixture of Ca-loaded liposomes, fibrinogen, and a Ca2+-dependent transglutaminase enzyme (either human recombinant FXIII or guinea pig liver transglutaminase) remained fluid indefinitely when stored at room temperature, but gelled rapidly when heated to 37 degrees C. SDS-PAGE of the reaction mixture revealed that gelation was due to enzymatic crosslinking of the alpha and gamma chains of fibrinogen, and oscillating rheometry revealed gel formation within 10 min of heating to 37 degrees C. This new approach may be useful for developing rapidly gelling injectable biomaterials that can be stored at room temperature and injected in a minimally invasive manner into a body tissue or cavity, upon which rapid solidification would occur. This versatile bioinspired strategy could be utilized for the delivery of biomaterials for tissue repair and reconstruction, and local site-directed drug delivery. PMID- 11214757 TI - Coating of Dacron vascular grafts with an ionic polyurethane: a novel sealant with protein binding properties. AB - The purpose of this study was to develop a novel sealant that would seal prosthetic vascular graft interstices and be accessible for protein binding. Crimped knitted Dacron vascular grafts were cleaned (CNTRL) and hydrolyzed in boiling sodium hydroxide (HYD). These HYD grafts were sealed using an 11% solids solution of a polyether-based urethane with carboxylic acid groups (PEU-D) via a novel technique that employs both trans-wall and luminal perfusion. Carboxylic acid content, determined via methylene blue dye uptake, was 2.3- and 4.2-fold greater in PEU-D segments (1.0+/-0.27 nmol/mg) as compared to HYD and CNTRL segments, respectively. Water permeation through PEU-D graft (1.1+/-2 ml/cm2 min( 1)) was comparable to collagen-impregnated Dacron (9.8+/-10 ml/cm2 min(-1)). Non specific 125I-albumin (125I-Alb) binding to PEU-D segments (18+/-3 ng/mg) was significantly lower than HYD and CNTRL segments. 125I-Alb linkage to PEU-D using the crosslinker EDC resulted in 5.7-fold greater binding (103+/-2 ng/mg) than non specific PEU-D controls. However, covalent linkage of 125I-Alb to PEU-D was 4.9- and 5.9-fold less than CNTRL and HYD segments with EDC, respectively. Thus, ionic polyurethane can be applied to a pre-formed vascular graft, seal the interstices and create "anchor" sites for protein attachment. PMID- 11214758 TI - Poly(ethylenimine)-mediated gene delivery affects endothelial cell function and viability. AB - Poly(ethylenimine) (PEI) was used to transfect the endothelial cell line EA.hy 926, and the secreted levels of three gene products, tissue-type plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), and von Willebrand Factor (vWF), were assessed via ELISA. We found that the levels of these gene products in cell supernatants increased by factors up to 16.3 (tPA), 8.3 (PAI-1), or 6.7 (vWF) times the levels recorded for untreated cells, and roughly correlated with the percentage of cells that expressed the reporter plasmid. Transfections carried out using promotorless constructs of the same reporter plasmid also yielded increases in tPA, PAI-1, and vWF to similar extents. Additionally, data regarding cell viability were gathered and found to inversely relate to both the effectiveness of the PEI used for transfection and the secreted levels of the three mentioned products. There appeared to be two distinct types of cell death, resulting from the use of either free PEI (which acts within 2 h) or PEI/DNA complexes (which cause death 7-9 h after transfection). Cells were also transfected by poly(L-lysine) and liposomal carriers, and increases in secreted tPA similar to those seen with PEI-mediated transfection were observed for positively transfected cells. The results of these investigations indicate that non-viral gene delivery can induce a state of endothelial cell dysfunction, and that PEI-mediated transfection can lead to two distinct types of cell death. PMID- 11214759 TI - Surface characteristics and in vitro biofilm formation on glass ionomer and composite resin. AB - In the initial stages of dental plaque formation, early colonizing bacteria bind to receptor structures in the pellicle, a proteinaceous film formed instantly after cleaning of the tooth surface. Dental restorative materials with surface characteristics different from the tooth might affect pellicle formation and the ability of bacteria to colonize the oral cavity. In this study (i) roughness and chemical composition of glass ionomer and composite resin surfaces before and after polishing, and (ii) the adsorption of salivary proteins and bacterial adherence to the pellicle-coated surfaces were examined. Compared with unpolished composite resin, unpolished glass ionomer had higher surface roughness, contained more inorganic, positively charged components, collected more proteins, and promoted better bacterial adherence. Polishing had the most pronounced effect on the composite resin, giving an enlarged and a rougher surface with a more inorganic character. Polishing the composite resin also led to increased biofilm formation. PMID- 11214761 TI - Investigation of thermal parameters and crytallisation in a ternary CaO-Na2O-P2O5 based glass system. AB - This paper presents the results of a study of the thermal properties of a range of phosphate-based glasses in the system CaO-Na2O-P2O5. The glasses had a fixed P2O5 content of 45 mol% and the CaO:Na2O ratio was varied. The glasses were produced and ground and their thermal properties measured using a Setaram differential thermal analyser (DTA). Initial data showed that for the high Na2O containing glass, NaPO3 forms and a second unidentified phase that is probably calcium rich. In the middle compositional region, multiple phases precipitated out and were identified as NaPO3 and Na4Ca(PO3)6. For the high CaO content glasses, Na4Ca(PO3)6 was the only phase formed. Further studies were carried out to examine whether the phases were bulk or surface nucleating, by grinding the samples to different particle sizes. From this data, it is evident that the NaPO3 forms via a bulk nucleation mechanism and that Na4Ca(PO3)6 forms via surface nucleation. The factors controlling this precipitation process are discussed and ionic radius as a controlling factor is hypothesised. PMID- 11214760 TI - Treatment of tooth fracture by medium-energy CO2 laser and DP-bioactive glass paste: the interaction of enamel and DP-bioactive glass paste during irradiation by CO2 laser. AB - Acute trauma or trauma associated with occlusal disturbance can produce tooth crack or fracture. Although several methods are proposed to treat the defect, however, the prognosis is generally poor. If the fusion of a tooth fracture by laser is possible, it will offer an alternative to extraction or at least serve as an adjunctive treatment in the reconstruction. We have tried to use a continuous-wave CO2 laser and a newly developed DP-bioactive glass paste (DPGP) to fuse or bridge tooth crack or fracture lines. Both the DP-bioactive glass paste and tooth enamel have strong absorption bands at the wavelength of 10.6 microm. Therefore, under CO2 laser, DPGP and enamel should have an effective absorption and melt together. The interface between DPGP and enamel could be regarded as a mixture of DPGP and enamel (DPG-E). The study focused on the phase transformation, microstructure, functional group and thermal behavior of DPG-E with or without CO2 laser irradiation, by the analytical techniques of XRD, FTIR, DTA/TGA, and SEM. The results of XRD showed that the main crystal phase in the DPG-E was dicalcium phosphate dihydrate (CaHPO4.2H2O). It changed into CaHPO4, gamma-Ca2P2O7, beta-Ca2P2O7 and finally alpha-Ca2P2O7 with increasing temperature. In the FTIR analysis, the 720 cm(-1) absorption band ascribed to the P-O-P linkage in pyrophosphate rose up and the intensities of the OH- bands reduced after laser irradiation. In regard to the results of DTA/TGA after irradiation, the weight loss decreased due to the removal of part of absorption water and crystallization water by the CO2 laser. SEM micrographs revealed that the melted masses and the plate-like crystals formed a tight chemical bond between the enamel and DPGP. We expect that DPGP with the help of CO2 laser can be an alternative to the treatment of tooth crack or fracture. PMID- 11214762 TI - Prevention of surface encrustation of urological implants by coating with inhibitors. AB - The encrustation of materials used for urological implants is as yet an unresolved problem. The crystallisation-inhibiting effect of the glycosaminoglycan heparin was used to reduce encrustation. Heparin was covalently bound to the surface of slotted-tube stents of tantalum and stainless steel using a spacer molecule. To verify the inhibition of crystallisation processes, reproducible in vitro tests and in vivo tests using the rat as animal model were carried out. The in vitro and in vivo experiments showed that the heparin coating has a significant influence on the encrustation of the surface. After 7 days in vitro and 120 days in vivo, heparin coated stents were free of encrustation, whereas the uncoated reference stents were extensively covered. PMID- 11214763 TI - A review of factors affecting fat absorption in hot chips. AB - Consumption of hot chips is a convenience food in most countries. Unfortunately, these are high in fat and contribute to fat-related diseases in societies with a high fat consumption. There is substantial scope through best-practice deep frying techniques for producing lower fat, high-quality chips. From a review of the literature, the main factors associated with a lower-fat content of chips are thick (>12 mm), straight cut chips; cryogenic freezing methods; low moisture content of potatoes (specific gravity >1.1); frying fat: chip volume ratio of 6:1; frying at optimal temperature (180 to 185 degrees C) during cooking and turning the temperature down (approximately 140 degrees C) and covering the vats during slack periods; vigorously shaking the basket and hanging it over the deep fryer to drain after frying; maintaining the quality of the frying fat by regularly skimming the cracklings, filtering the fat, and topping up the fryer with fresh fat; keeping the fat turnover <5 days; regular cleaning of frying equipment. It is important that all deep frying operators are adequately trained in these techniques. It is also important that the frying medium is low in saturated and trans fatty acids (<20%) because of their effects on blood lipids and low in linolenic acid (<3%) because it is readily degraded. The widespread implementation of best-practice deep-frying would reduce fat content of hot chips and thus lower overall fat consumption. PMID- 11214764 TI - A review on grain and nut deterioration and design of the dryers for safe storage with special reference to Turkish hazelnuts. AB - Turkey produces about 80% of the total hazelnut crop of the world. About 75% of the production are exported. In Turkey hazelnuts are traditionally sun dried, and may be subject to mold growth and subsequent mycotoxin formation due to prolonged drying time under humid and rainy weather conditions. Drying hazelnuts in a reasonable time after harvest is necessary for mycotoxin-free, high-quality products. In general, nuts and cereals contaminated by the toxins pose a potential hazard not only to the people of the producer countries, but also to people of the importing countries, if they should be regarded as safe by inefficient sampling plans, therefore preventing toxin formation actually benefits very large populations. Deterioration and health hazards associated with toxin contaminated hazelnuts and other nuts and cereals have similar causes and consequences; therefore, deterioration of the nuts and cereals in storage has been reviewed by considering as many grains and nuts as possible, then special reference was made to hazelnuts. Proper preharvest practices followed by proper drying and safe storage reduces the hazards associated with contamination by the toxins. This article reviews the pre- and post-harvest practices, and the grain- and nut-drying systems required for toxin-free products. Because drying is the major unit operation involving this process, the drying systems and the mathematical models required for their design is also discussed. PMID- 11214765 TI - Interaction between angiotensin-converting enzyme inhibitors and aspirin: a review. AB - Aspirin and angiotensin-converting enzyme inhibitors (ACEIs) are often associated for the treatment of coronary disease and/or chronic heart failure, but conclusions of some prospective and retrospective studies show a possible negative interaction between aspirin and ACEIs. ACEIs inhibit the conversion of angiotensin I to angiotensin II and also the catabolism of bradykinin, which results in increased synthesis of vasodilatory agents [prostaglandins and nitric oxide (NO)], whereas aspirin inhibits prostaglandin synthesis. Thus, a potential interaction from the opposing effects of aspirin and ACEIs could affect the metabolism of bradykinin. We conducted an extensive Medline search, as well as a manual search, of published literature including pharmacodynamic studies and clinical trials concerning the impact of aspirin on the effect of ACEIs in hypertension, coronary disease and chronic heart failure. A review of this literature shows five studies in hypertension (all prospective and using blood pressure as the main criterion of assessment), five in coronary disease (three retrospective and two prospective trials, four of which use mortality as the criterion of assessment) and 13 in chronic heart failure (eight using haemodynamic measurements of which seven are prospective--one prospective study using pulmonary tests, four using clinical events including mortality as criterion of assessment of which two are prospective). The counteraction of ACEI efficacy by aspirin is demonstrated in one out of five studies in hypertension, one out of four of studies in coronary disease and nine out of thirteen in chronic heart failure. This counteraction is more often observed with high dosages of aspirin (greater than 250 mg/day, four out of six studies) and less often with lower dosages (less than or equal to 250 mg/day, three out of 11 studies). These studies are retrospective analyses or use haemodynamic end points, so there is as yet no methodological argument strong enough to contraindicate the aspirin-ACEI association or to prove the clinical relevance of this interaction. In conclusion, prospective studies using mortality as a criterion of assessment are needed to offer the practitioner the answer to the question of ACEI-aspirin association. PMID- 11214766 TI - Inhibition of puerperal lactation with 2-mercaptopropionyl-glycine. AB - OBJECTIVES: Thiols (sulfydryl compounds) have a prolactin-lowering effect in animals. The purpose of our study was to evaluate the effects of orally administered N-2-mercaptopropionyl-glycine (tiopronin) on suppression of lactation and plasma prolactin (PRL) levels in a group of women in the puerperium. METHODS: One hundred women aged 17-37 years were studied. We divided our population in four groups (25 patients in each group). In group I, no medication was administered but only conservative measures were taken (restriction of fluid intake, ice-bags applied on the breasts, tight breast binders). Subjects in group II received tiopronin (200 mg/day) for 14 days. In group III, tiopronin (500 mg/day) was administered for 14 days. Subjects in group IV, took bromocriptine (5 mg/day) for 14 days. Assessment of suppression of lactation was performed clinically and laboratory determinations were obtained before and after 1, 2, 3, 4, and 14 days of treatment. Furthermore, in seven healthy women plasma PRL responses to thyrotropin-releasing hormone (TRH) before and after one week of tiopronin therapy (500 mg/day) were studied. RESULTS: Statistically significant higher percentages of success of lactation suppression were obtained with tiopronin (84% and 88%) and bromocriptine (96%) compared to conservative treatment (60%). In the four groups a significant decrease of PRL was observed. However, in women who received tiopronin and bromocriptine, the levels of PRL after 14 days of therapy were lower compared to the conservative treatment group. Moreover, in the tiopronin groups and the bromocriptine group, lactation was stopped earlier. In the first group (conservative measures) the lactation was suppressed after 13.3+/-5.4 days of treatment. In the groups who received tiopronin (200 mg/day and 500 mg/ day) lactation was suppressed after 4.4+/-1.7 and 4.3+/-1.6 days of treatment. In the bromocriptine group the lactation was stopped after 1.2+/-0.4 days. Bromocriptine treatment was associated with more frequent side effects than the tiopronin. CONCLUSION: Administration of tiopronin in low to moderate doses is effective in suppression of puerperal lactation. PMID- 11214767 TI - Assessment of the systemic effects of beclomethasone dipropionate inhaled via Easyhaler or via Diskhaler in healthy male volunteers. AB - OBJECTIVE: The objective of this study was to compare the systemic effects of a moderate dose (800 microg/day) with the highest recommended dose (1600 microg/day) of beclomethasone dipropionate (BDP) inhaled via either Easyhaler or Diskhaler in 15 healthy adult male volunteers. METHODS: This was an open, placebo controlled, randomised study conducted according to a crossover design and consisting of a 1-week baseline period and five 1-week treatment periods, each separated by a 1-week washout period. Subjects received in randomised order 800 microg/day BDP via Easyhaler, 1600 microg/day BDP via Easyhaler, placebo via Easyhaler, 800 microg/day BDP via Diskhaler and 1600 microg/day BDP via Diskhaler. Subjects inhaled BDP twice daily at 0800 hours and 2000 hours. The last dose of each period was inhaled at the study site. Venous blood samples were drawn prior to and at 2-hour intervals for 20 h after the last dose. Serum cortisol area under the curve (AUC0-20) and morning serum cortisol values were determined using radioimmunoassay. Urine for analysis of urine cortisol/creatinine ratios (UCC) was collected over a 12-h period after the last dose of each treatment period. RESULTS: According to serum cortisol values, no systemic effects were detected with BDP 800 microg/day inhaled via Easyhaler. The mean (+/-SD) change in serum cortisol AUC0-20 was +118.3+/-1391 nmol h/l compared with placebo. Mean (SD) changes from placebo in serum cortisol AUC0-20 values after BDP 1600 microg/day were--546.3+/-1004 nmol h/l with Easyhaler and -769.3+/ 596 nmol h/l with Diskhaler. However, there were no statistically significant differences in systemic bioactivity between the active treatments. Morning serum cortisol levels and UCC ratios were consistent with the serum cortisol AUC0-20 data. CONCLUSIONS: In conclusion, BDP 800 microg/day inhaled via Easyhaler did not reduce serum cortisol AUC0-20 compared with placebo. Although the decrease in hypothalamic pituitary-adrenal (HPA) axis function after BDP 1600 microg/day was statistically significant compared with placebo, the reduction was small and similar with both devices. PMID- 11214768 TI - Efficacy of combination of atorvastatin and micronised fenofibrate in the treatment of severe mixed hyperlipidemia. AB - OBJECTIVES: In patients with mixed lipid disorders, monotherapy may not effectively control all lipid abnormalities. We undertook this study to assess the efficacy of fenofibrate in combination with atorvastatin in patients with severe mixed dyslipidemia. METHODS: This was an 18-week, open-label study conducted in our lipid clinic. After a 6-week dietary baseline phase, patients received 200 mg/day micronised fenofibrate for 6 weeks. At the end of this period the subjects discontinued this treatment and received 40 mg/day atorvastatin for 6 weeks. Finally 200 mg/day of micronised fenofibrate was added to the statin therapy. RESULTS: Administration of micronised fenofibrate reduced serum triglycerides (P < 0.01) and total cholesterol and low-density lipoprotein (LDL) cholesterol (P < 0.05 for both parameters), while it evoked a significant increase in serum high-density lipoprotein (HDL) cholesterol levels (P < 0.05). Atorvastatin monotherapy induced a more pronounced decrease of total and LDL cholesterol. However, plasma triglycerides, although significantly lower than baseline values (P < 0.05), were higher than the values observed during treatment with fenofibrate. Moreover, serum HDL cholesterol concentrations were higher during fibrate therapy than during the statin one. During the combination therapy, the decrease in triglycerides was greater than that observed with fenofibrate alone, while the decrease in LDL cholesterol was more pronounced than that observed with atorvastatin alone. CONCLUSION: The combination of atorvastatin with micronised fenofibrate in patients with severe mixed dyslipidemia may have a favourable effect on some major coronary artery disease risk factors. PMID- 11214769 TI - Blood pressure responses to whole-body cold exposure: effect of carvedilol. AB - OBJECTIVE: The aim of this study was to test the effects of carvedilol on blood pressure (BP) and heart rate (HR) during whole-body cold exposure in hypertensive and normotensive subjects. METHODS: Ten hypertensive and twelve normotensive subjects were exposed to cold (-15 degrees C, wind 3.5 m/s) three times for 15 min with a 1-week interval between the exposures. The study design was made according to a randomised double-blind, crossover method. Before the cold exposures the subjects ingested carvedilol or placebo once a day (carvedilol 12.5 mg/day for 2 days and then 25 mg/day for 5 days) for 1 week. The systolic (SBP) and diastolic (DBP) blood pressure and HR were measured every 3 min during the test procedures using an indirect ambulatory blood pressure monitor device (ABPM 02, Meditech Co.). RESULTS: In the hypertensive group, the cold exposure increased SBP/DBP from 119/75 mmHg to 143/96 mmHg during carvedilol treatment (P<0.001) and from 132/85 mmHg to 159/106 mmHg during placebo (P<0.001). In the normotensive group the cold exposure increased SBP/DBP from 112/72 mmHg to 142/93 mmHg during carvedilol treatment (P<0.001) and from 121/75 mmHg to 147/98 mmHg during placebo (P<0.001). In the hypertensive group, the levels of SBP, DBP and MAP (mean arterial pressure) were significantly lower with carvedilol than with placebo during the cold exposure although carvedilol did not affect the cold induced rise of the BP. The BPs were lower also with carvedilol in the normotensive group than the placebo during the cold exposure, but the differences were smaller than in the hypertensive group. Carvedilol decreased the BP more the higher the initial mean SBP/DBP was with placebo during the cold exposure. CONCLUSION: Carvedilol reduced the BP during the cold exposure, especially in the hypertensive subjects but also in normotensive ones, without effect on the cold induced rise of the BP. PMID- 11214770 TI - Effects of grapefruit juice on the stereoselective disposition of nicardipine in humans: evidence for dominant presystemic elimination at the gut site. AB - OBJECTIVES: To assess relative roles of the intestinal and hepatic stereoselective metabolism of nicardipine in an oral first-pass disposal with and without grapefruit juice intake. METHODS: The kinetic profiles of (+)- and (-) nicardipine were studied in the six normal healthy male volunteers who received oral (40 mg) and intravenous (2 mg) racemic nicardipine, first with water and second with grapefruit juice. Both the enantiomers were determined by the stereoselective high-performance liquid chromatographic method, and hemodynamic parameters (arterial blood pressure, heart rate, and electrocardiogram) were assessed when each blood sample was taken. RESULTS: Grapefruit juice compared with water intake caused a significant (P < 0.05) increase in the mean oral (+)- and (-)-nicardipine bioavailability (Fobs) (48.6+/-5.0% and 105.6+/-7.8%) and dose-absorbed (Fabs) available fraction unmetabolized at the gut (Fg) (48.2+/ 5.6% and 110.9+/-8.8%, respectively) with no significant change in the hepatic first-pass effect. However, all of the mean kinetic parameters of both the enantiomers after the intravenous dosing of racemic nicardipine did not differ between the grapefruit juice- and water-intake trial phases. The mean percentage changes in oral AUC (43.1+/-3.4% in [+]-nicardipine and 90.9 6.4% in [-] nicardipine, or Fobs) and Fabs Fg by grapefruit juice tended to be greater for ( )-nicardipine than for (+)-nicardipine and the mean oral (+)/(-)-nicardipine AUC ratio was significantly reduced by grapefruit juice (from 2.25+/-0.37 to 1.75+/ 0.28) (P < 0.05). Except for heart rates, which were greater with grapefruit juice (P < 0.05) at 1 and 2 h after the oral dose of nicardipine, the mean hemodynamic variables did not differ between the two trial phases. CONCLUSION: We conclude that the gut is the major presystemic disposal site of racemic nicardipine in humans. Grapefruit juice appears to affect this metabolic disposal of (-)-nicardipine to a somewhat greater extent compared with that of (+) nicardipine, with an early postdose transient tachycardia after the oral dosing of racemic nicardipine. PMID- 11214771 TI - In-vivo indices of CYP2D6 activity: comparison of dextromethorphan metabolic ratios in 4-h urine and 3-h plasma. AB - OBJECTIVES: Dextromethorpan (DM) is widely used as a probe drug to assess in vivo the activity of the cytochrome P450 2D6 (CYP2D6). The aim of the study was to compare metabolic ratios (MRs) of DM to dextrorphan (DEX) in plasma and urine. We examined, separately in urine and plasma, the relationships between the MRs which are based on DEX and those involving the sum of DEX and a secondary metabolite hydroxymorphinan (HM). Furthermore, we compared the MRs in plasma obtained with and without hydrolysis of DEX glucuronides. METHODS: Concentrations of DM and metabolites in urine and plasma were determined by HPLC after a single oral dose of 30 mg DM hydrobromide to 101 healthy Caucasian subjects. Urine was collected over the time interval 0-4 h after the dose and plasma was obtained from 95 subjects 3 h after administration. RESULTS: Six subjects (5.9%) were of poor metaboliser (PM) phenotype (urinary DM:DEX ratio >0.3). A good correlation (r2 = 0.777, P < 0.00001) was observed between the metabolic ratios of DM:DEX in plasma and urine. There was an excellent correlation, both in plasma and urine, between the log-transformed ratios of DM:DEX and of DM to the sum of molar concentrations of DEX and HM (r2 > 0.996, P < 0.00001). Plasma samples of 89 subjects (83 EM and 6 PM) were analyzed without deconjugation of DEX glucuronide also. The correlation between the plasma ratios of DM:DEX based on unconjugated DEX and those involving glucuronide (r2 = 0.793, P < 0.00001) was comparable to that reported by other authors on urine. CONCLUSION: In healthy Caucasian subjects, the MRs of DM to DEX in plasma obtained at 3 h correlated reasonably well with those in urine collected over the time interval 0-4 h after the dose. Nevertheless, repeatability of this plasma index should be determined before its wide use can be recommended. Finally, the interindividual variation in DEX metabolism to HM (catalyzed by CYP3A) contributes only minimally to the interindividual variability of the MRs. PMID- 11214773 TI - Pharmacokinetics of esomeprazole after oral and intravenous administration of single and repeated doses to healthy subjects. AB - OBJECTIVE: To study the pharmacokinetics of esomeprazole, one of the optical isomers of omeprazole, after 20 mg or 40 mg single and repeated oral and intravenous administration to healthy subjects. The main metabolites of esomeprazole were also assessed after the 40-mg oral dose. METHODS: In two separate studies, 16 healthy male subjects and 16 healthy male and female subjects received intravenous doses of 20 mg and 40 mg esomeprazole, respectively, on the first investigation day. After a washout period of 5-14 days, the same doses (20 mg as a solution and 40 mg as a capsule) were given orally for 5 days and then again intravenously on day 6. Blood samples for determination of esomeprazole and its metabolites were collected 12 h or 24 h post-dose and were analysed using normal-phase liquid chromatography with ultraviolet (UV) detection. Pharmacokinetic parameters of esomeprazole and its metabolites were estimated using non-compartmental analysis. Geometric means and ratios of the geometric means together with 95% confidence intervals (CI) of the pharmacokinetic parameters were calculated using analysis of variance (ANOVA). RESULTS: Plasma clearance (CL) of esomeprazole decreased from 22 l/h to 16 l/h and from 17 l/h to 9 l/h following repeated dosing of 20 mg and 40 mg, respectively. Total area under the plasma concentration-time curve (AUC) increased (from 1.34 micromol x h/l to 2.55 micromol x h/l) with absolute bioavailability (F) being 50% on day 1 and 68% on day 5 after the 20-mg oral dose. AUC increased (from 4.32 micromol x h/l to 11.21 micromol x h/l) with F being 64% on day 1 and 89% on day 5 after the 40-mg oral dose. The plasma levels for esomeprazole sulphone were substantially higher on day 5 than on day 1, while those for 5-hydroxy esomeprazole were marginally higher on day 5 than on day 1 following repeated oral dosing of 40 mg esomeprazole. No side effects attributable to esomeprazole were noticed. CONCLUSION: The increased AUC of esomeprazole with repeated dosing is probably due to a combination of a decreased first-pass elimination and a decreased systemic clearance. PMID- 11214772 TI - Mycophenolic acid glucuronidation and its inhibition by non-steroidal anti inflammatory drugs in human liver and kidney. AB - OBJECTIVE: The aims of this investigation were to study the glucuronidation of mycophenolic acid (MPA) in human liver and kidney and to search for a compound that inhibits MPA glucuronidation among the non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: A sensitive and reproducible radiometric assay was developed to measure the rate of MPA glucuronidation in human liver and kidney microsomes. The assay employed uridine 5'-diphosphate-[U-14C]-glucuronic acid (UDPGA) and MPA glucuronide was isolated by TLC. The final concentrations of UDPGA and MPA necessary were 1 mM (liver), and MPA concentration was 0.5 mM (kidney). The inhibition of MPA glucuronidation was studied with 18 NSAIDs and tacrolimus. RESULTS: Glucuronosyl transferase activity followed Michaelis-Menten kinetics and the Km (mean +/- SD; mM) was 0.31+/-0.06 (liver; n = 5) and 0.28+/-0.07 (kidney; n = 5; P = 0.555); the Vmax (mean SD; nmol/mg per minute) was 5.2+/-1.4 (liver; n = 5) and 10.5+/-1.2 (kidney; n = 5; P = 0.0005). The MPA glucuronidation rates (mean +/- SD; nmol/min/mg) were 3.3+/-0.9 (liver; n = 10) and 7.8+/-1.5 (kidney; n = 10; P = 0.0002). The rate of MPA glucuronidation ranged between 2.0 and 5.1 nmol/ mg per minute with a 2.5-fold variation (liver) and between 5.7 and 9.8 nmol/mg per minute with a 1.7-fold variation (kidney). The inhibition study was performed in liver and revealed that the percentage of control ranged from 8%+/ 3% (niflumic acid) to 119%+/-16% (Ketoralac). The inhibition curves for MPA glucuronidation rate were determined with the four most effective inhibitors: niflumic acid, flufenamic acid, mefenamic acid and diflunisal. Their IC50 estimates (microM) were 8+/-1, 19+/-9, 63+/-8 and 109+/-15, respectively (liver), and 8+/-2, 13+/-2, 49+/-4 and 122+/-18, respectively (kidney). The IC50 estimate for niflumic acid was eightfold lower than the peak plasma levels after a single oral dose of 250 mg of this drug. CONCLUSION: The human liver and kidney are important sites of MPA glucuronidation. MPA glucuronidation was inhibited to various extents by different NSAIDs and the four most effective inhibitors were niflumic acid, flufenamic acid, mefenamic acid and diflunisal. These drugs have similar molecular structures consisting of two aromatic rings bearing a carboxylic group. PMID- 11214774 TI - Influence of continuous veno-venous haemodiafiltration and continuous veno-venous haemofiltration on the pharmacokinetics of fluconazole. AB - OBJECTIVE: To compare the elimination of fluconazole by continuous veno-venous haemodiafiltration (CVVHD) and continuous veno-venous haemofiltration (CVVH) at different dosages. INTERVENTION: Patients received doses of 400 mg (n=3), 600 mg (n=1) or 800 mg (n=2) fluconazole as a short-time infusion once a day. Patients underwent CVVHD the first day and CVVH the second day. CVVHD and CVVH were performed using an acrylonitrile hollow-fibre filter at a constant blood flow of 90 ml/min and a substitution flow of 1000 ml/h (predilution). During CVVHD, the dialysate flow was 1000 ml/h. Ultrafiltration rates were 1158+/-90.5 ml/h during CVVHD and 1167+/-81.6 ml/h. Serum and ultrafiltrate/dialysate concentrations of fluconazole were determined on nine occasions over 24 h. PARTICIPANTS: Six critically ill patients with acute renal failure (ARF) and serious fungal infection. RESULTS: Extracorporeal clearance (CVVHD 30.5+/-6.0 ml/min, CVVH 17.5+/-4.0 ml/min) and total clearance of fluconazole (CVVHD 37.9+/-4.4 ml/min, CVVH 25.3+/-6.5 ml/min) were significantly higher during CVVHD (P < 0.05). During CVVHD, the sieving coefficient (S(CVVHD)) was 0.88 (range 0.54-1) and the elimination half-life (t1/2) was 14.8-35.1 h. During CVVH, the S(CVVH) was 0.96 (range 0.56-1.02) and t1/2 was 24.0-51.6 h. CONCLUSIONS: A daily dosage of 400 800 mg fluconazole is recommended in the treatment of life-threatening fungal infections in critically ill patients undergoing CVVHD since the clearance of CVVHD may considerably exceed the clearance in patients with normal renal function, which is about 20 ml/min. Drug monitoring is highly recommended for these patients. PMID- 11214776 TI - Consideration of endogenous backgrounds in pharmacokinetic analyses: a simulation study. AB - OBJECTIVE: The pharmacokinetic analysis of biologic compounds is frequently disturbed by the presence of endogenous levels, which cannot be discerned from exogenous levels. The frequently used method of subtracting baseline levels from subsequent measurements was compared to a fully adjusted regression model in a simulation study. METHODS: Simulations (5,000 each) were carried out for a standard one-compartment model with rich (n = 10) and poor (n = 6) postdose sampling, using unweighted as well as two-weighted types of non-linear regression. RESULTS: Whereas the fully adjusted model performed properly across various scenarios, the subtraction method showed a noteworthy bias (up to 14%) for area under the curve (AUC) and elimination half-life with weighted non-linear regression. For estimation of the Cmax parameter using any weighting scheme, and of any parameter using unweighted non-linear regression, the two methods performed equally well. As expected, poor in contrast to rich sampling resulted in larger coefficients of variation, but also in increasing failures (4.4%) of the regression algorithm (failure to converge, negative Cmax or half-life) for the subtraction method when it was combined with the weighting scheme giving highest weight to small concentrations. CONCLUSION: The risk of biased results may result from the subtraction method, which may also affect the analysis of dose linearity, bioequivalence and population kinetic studies with biologic compounds. When background endogenous levels are not negligible, a fully adjusted model is recommended. PMID- 11214775 TI - CYP2D6 genotype and antipsychotic-induced extrapyramidal side effects in schizophrenic patients. AB - OBJECTIVE: In order to evaluate whether poor metabolizers (PM) of debrisoquine are overrepresented among patients with acute dystonic reactions and chronic movement disorders associated with the administration of antipsychotic drugs, the CYP2D6 genotype was determined in schizophrenic patients. METHODS: Allele status for CYP2D6*3, CYP2D6*4, CYP2D6*5, and CYP2D6*6 as well as gene duplication was determined by allele-specific PCR, long-PCR and restriction fragment length polymorphism analysis (RFLP) in 119 schizophrenic patients (99 males and 20 females). All subjects were treated with antipsychotics metabolized, at least partially, by this isozyme. Sixty-three of the patients (52.9%) had a history of extrapyramidal side effects (EPS), while 56 (47.1%) had not experienced such problems (controls). RESULTS: Sixty-five patients (54.6%) were homozygous for a functional CYP2D6*1 allele, 44 (37.0%) were heterozygous for detrimental alleles, and 4 (3.4%), who carried two detrimental alleles, were classified as PM. In six patients (5.0%) duplication of a functional CYP2D6 gene was found, and they were consequently classified as ultrarapid metabolizers (UM). Homo- and heterozygous extensive metabolizers (EM) as well as UM were equally distributed between patients with and without EPS, whereas all the PM had a history of EPS. No significant differences in allele frequencies between the two groups were found. CONCLUSION: Although the results cannot be considered conclusive due to the small number of PM patients in our study, the PM genotype may be a predisposing factor for antipsychotic-induced EPS. Knowledge of the CYP2D6 genotype, before starting antipsychotic therapy, might be useful in identifying subjects at risk of developing EPS. PMID- 11214777 TI - Correlation between acetylation phenotype and genotype in Chinese women. AB - OBJECTIVE: The acetylation polymorphism is a common inherited variation in human drug and carcinogen metabolism. Because N-acetyltransferase (NAT2) is important for the detoxification and/or bioactivation of drugs and carcinogens, this polymorphism has important implications in therapeutics and cancer susceptibility. A high correlation between acetylation phenotype and genotype has been demonstrated in several studies. However, no such data exist for Chinese females. The aim of the present study was to compare acetylation phenotype with NAT2 genotype in a population of primarily non-smoking Chinese females. METHODS: In the present study, the correlation between N-acetyltransferase activity and NAT2 genotype was evaluated in 103 unrelated Chinese female controls derived from a hospital-based case-control study of lung cancer in Singapore. Acetylation phenotype and genotype were respectively determined using caffeine and an allele specific polymerase chain reaction (PCR). RESULTS: The proportions of rapid and slow phenotypes were 78% and 22%, respectively, while the distribution of rapid (heterozygotes and homozygotes combined) and slow acetylator genotypes was 76% and 24%, respectively. The distribution of the various NAT2 genotypes did not differ significantly (chi2 = 1.45, P > 0.05) from that predicted by the Hardy Weinberg Law. All slow acetylators were accurately predicted (100%), whereas 2 of 80 rapid acetylators were erroneously predicted as slow (2.5%). The overall prediction rate of the PCR-based test for the acetylation phenotype was at 98.1% in our Chinese population. CONCLUSION: Our results suggest that genotyping with PCR may well become the preferred method for the determination of acetylation polymorphism in epidemiological studies in this Asian population. PMID- 11214778 TI - Effect of grapefruit juice on pharmacokinetics and pharmacodynamics of verapamil enantiomers in healthy volunteers. AB - OBJECTIVES: To determine the effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of S- and R-verapamil (given as racemates) at steady state. METHODS: Nine healthy male volunteers followed a randomised cross-over study comprising two treatment periods. Pretreatments of 200 ml orange juice (control) or grapefruit juice twice daily for 5 days and 120 mg verapamil (orally) twice daily for 3 days were given. On the study day, the subjects received the morning dose of verapamil with either orange juice (control) or grapefruit juice. Plasma and urine samples were collected for measurement of S- and R-verapamil and the metabolites S- and R-norverapamil. Blood pressure (BP), heart rate (HR) and PR interval were monitored. RESULTS: During the grapefruit juice period, the steady state peak and trough concentrations of S-verapamil were moderately increased (peak 41+/-25 ng ml(-1) versus 26+/-13 ng ml(-1), trough 14+/-7 ng ml(-1) versus 12+/-6 ng ml(-1), P=0.08). Grapefruit juice significantly increased the area under the plasma concentration-time curve during the 12-h dose interval (AUC0-12 h) of S-verapamil by 36% (292+/-146 ng h ml(-1) versus 215+/-102 ng h ml(-1), P=0.04). Similar results were obtained for peak and trough concentrations of R verapamil. The AUC0-12 h of R-verapamil was increased by 28% (1022+/-412 ng h ml( 1) versus 800+/-316 ng h ml(-1), P=0.04). Elimination half-life and renal clearance of both S- and R-verapamil were not affected. Considerable inter subject variability in interaction was shown. There were no significant differences in the pharmacodynamic parameters (BP, HR and PR-interval). CONCLUSIONS: The present study has demonstrated an interaction between verapamil and grapefruit juice, which is likely due to an inhibition of intestinal metabolism resulting in increased oral bioavailability. PMID- 11214779 TI - Citalopram pharmacokinetics in patients with chronic renal failure and the effect of haemodialysis. AB - OBJECTIVE: To study the effects of severe renal failure and haemodialysis on the pharmacokinetics of citalopram. METHODS: Four patients with renal failure undergoing haemodialysis and eight healthy controls were given a single dose of citalopram. The concentrations of citalopram and its metabolites desmethylcitalopram and didesmethylcitalopram were measured in serum and urine. On a different day, the four patients undergoing haemodialysis were given another single dose of citalopram, and the drug concentrations were measured in serum from the artery leading to the dialyser and in the dialysate. In addition, one anuric patient treated with citalopram on a regular basis was included in the study. RESULTS: There were no significant differences between the two groups in any of the pharmacokinetic parameters with the exception of the renal clearance of citalopram, which was significantly lower in the renal failure group than in the control group (1.70 ml/min versus 66.2 ml/min, P<0.001). Oral clearance of citalopram was almost identical in the two groups (452 ml/min versus 456 ml/min). The process of haemodialysis cleared about 1% of the dose as citalopram and 1% as desmethylcitalopram only. CONCLUSION: Severe renal failure does not affect the pharmacokinetics of citalopram and modification of the usual citalopram dose does thus not seem to be necessary. The contribution of haemodialysis to the total elimination of citalopram is negligible. PMID- 11214780 TI - Pharmacokinetic and pharmacodynamic interactions between the novel calcium sensitiser levosimendan and warfarin. AB - OBJECTIVE: To study the effects of possible interactions between levosimendan and warfarin on pharmacokinetics and pharmacodynamics. Furthermore, the effects of levosimendan on blood coagulation were investigated. METHODS: Open, randomised cross-over design with two treatment phases was used. During one phase, levosimendan (0.5 mg four times daily) was given orally to ten healthy subjects for 9 days. On the fourth treatment day with levosimendan, a single oral dose of warfarin (25 mg) was given. Pharmacokinetic parameters of levosimendan from the third and fourth treatment days were compared with each other. During the other treatment phase the subjects received only a single dose of warfarin. Pharmacokinetic parameters of warfarin alone were compared with those determined after concomitant administration of levosimendan. Changes in blood coagulation parameters were evaluated after levosimendan and warfarin alone and after concomitant administration. RESULTS: Warfarin did not change the pharmacokinetics of levosimendan. The distribution volume of warfarin was higher and elimination half-life shorter after concomitant levosimendan administration than after warfarin alone. However, concomitant levosimendan administration did not potentiate the effects of warfarin on blood coagulation assessed using activated partial thromboplastin time (APTT) and thromboplastin time (TT-SPA). Levosimendan alone for 3 days did not change APTT or TT-SPA values. There were no changes in the protein binding of levosimendan or warfarin upon concomitant administration. Continuous treatment with oral levosimendan caused headache, which was probably due to cerebral vasodilation. CONCLUSIONS: Concomitant levosimendan administration did not potentiate the effect of warfarin on blood coagulation after a single dose. Levosimendan itself had no effects on blood coagulation. PMID- 11214781 TI - Effects and pharmacokinetics of oral glibenclamide and glipizide in Caucasian and Chinese patients with type-2 diabetes. AB - The effects and kinetics of oral glibenclamide (Gb) and glipizide (Gz) were studied in Caucasian and Chinese patients (ten in each group) with type-2 diabetes. In randomised order, 2.5 mg Gb, 2.5 mg Gz or placebo was given orally before the administration of 75 g oral glucose. Concentrations of insulin and proinsulin were determined using radioimmunoassay (RIA) without cross reactivities, and sulphonylurea concentrations were determined using high performance liquid chromatography (HPLC). There were no significant interethnic differences in Gb or Gz effects whether on glucose, insulin or proinsulin/insulin ratio at any time point. Following Gz, however, Chinese patients had greater increments of serum proinsulin at 10-30 min compared with Caucasians. Apart from the maximum plasma concentration (Cmax) and area under the plasma concentration time curve (AUC) of Gz being higher among the Chinese, no significant interethnic differences in pharmacokinetics were found. It appears that the same dosage principles could be used for Caucasian and Chinese patients with type-2 diabetes when Gb or Gz are prescribed. PMID- 11214782 TI - Steady-state dispositions of valproate and diflunisal alone and coadministered to healthy volunteers. AB - OBJECTIVE: The effects of coadministration of the non-steroidal anti-inflammatory drug diflunisal (DF) on glucuronidation and beta-oxidation of the antiepileptic agent valproic acid (VPA), and of VPA on DF glucuronidation, were studied in human volunteers. METHODS: Seven healthy male volunteers received sodium valproate (NaVPA, 200 mg) orally twice daily for 7 days, after which all drug intake ceased for 1 month. The volunteers then took DF (250 mg) orally twice daily for 7 days. Both drugs were then taken (at the same doses as previously) twice daily for 7 days. On day 7 of each dosing phase, serial blood samples and all urine passed over the 12-h inter-dosing interval were collected. VPA, DF and selected metabolites were analysed using validated methods. Statistical comparisons of pharmacokinetic parameters were made using paired Student's t tests. RESULTS: Mean plasma concentrations of total VPA were lower and apparent plasma clearances significantly higher during DF coadministration. This was associated with a significant 20% increase in the unbound fraction of VPA (from 6.6+/-1.3% to 7.9+/-1.8%). The apparent clearance of unbound VPA was not different. There was no evidence of any significant effect of DF coadministration on VPA metabolism: urinary recoveries of and formation clearances to urinary VPA glucuronide, E-2-en-VPA, 3-oxo-VPA and 4-en-VPA were not significantly altered. However, there was a highly significant 35% increase in the area under the plasma concentration-time curve from 0-12 h (AUC0-12h) of 3-oxo-VPA and its renal clearance was lower, though not significantly so. VPA coadministration had no effect on DF pharmacokinetics or formation clearances of DF to its acyl glucuronide (DAG), phenolic glucuronide (DPG) or sulfate (DS) conjugates. However, plasma AUC0-12h values of the glucuronides were significantly lower and their renal clearances higher (though significantly so only in the case of DPG) during VPA coadministration. CONCLUSIONS: Steady-state coadministration of VPA and DF leads to a significant displacement of VPA from plasma protein binding sites. There was no evidence of competition for glucuronidation capacity or other metabolic interactions. Rather, the interactions detected appeared to be renal in nature, with renal clearance of 3-oxo-VPA being reduced by DF coadministration, and renal clearance of DPG and perhaps DAG being increased by VPA coadministration. PMID- 11214783 TI - Different versions of the anatomical therapeutic chemical classification system and the defined daily dose--are drug utilisation data comparable? AB - OBJECTIVE: To investigate whether published drug utilisation studies contain satisfactory references to the ATC/DDD version applied and thus are usable for comparative purposes. METHODS AND RESULTS: A literature survey of drug utilisation studies was made. Seventy-three articles were identified by two Medline searches, one in 1996 and another in 1998. The articles were classified into four different groups. Groups 1 and 2 give proper references to the defined daily doses (DDDs) used in the studies, either by full reference to the version of the ATC Index with DDDs or by listing the actual DDDs used. The articles in groups 1 and 2 represent 46% of the articles in the survey. The articles classified in groups 3 and 4 give references only to general articles about the anatomical therapeutic chemical classification (ATC)/DDD system or no references at all. Fifty-four percent of the articles in the survey were classified in these groups. In these articles it is not possible to identify which DDDs have been used in the presentation of drug consumption data. CONCLUSIONS: According to the results from our literature survey, it is not common practice to include the ATC codes and the DDD values used or to make reference to the versions of the ATC/DDD index used when results from drug utilisation studies are published. One possible reason for this might be little or no knowledge about the ATC/DDD system as a dynamic system in which alterations are made annually. The lack of references to the actual DDDs used in the studies make comparisons between different data sets difficult and misleading. PMID- 11214784 TI - Attitudes to reporting adverse drug reactions in northern Sweden. AB - OBJECTIVES: This study was designed to investigate attitudes of general practitioners (GPs) and hospital physicians in Sweden towards spontaneous reporting of adverse drug reactions (ADRs). METHOD: Two areas in the northern region of Sweden were selected for the study. A knowledge and attitude questionnaire followed by a reminder letter 2 weeks later was addressed to all GPs and hospital physicians in the study areas. RESULT: The total response rate from the study areas was 748 of the 1274 questionnaires sent out (58.7%). Of those who responded, 236 were GPs, 433 were hospital physicians and 79 had other positions. Of the responders, 252 stated that they had never reported any ADR and 488 that they had reported at least once in their career. Issues that came out as important in the decision to report or not to report were whether the reaction was considered well-known or not, the severity of the reaction, hesitance to report only on suspicion, lack of knowledge of existing rules, giving priority to other matters and lack of time to report ADRs. Only minor differences in these regards were observed between male and female physicians. CONCLUSION: Our investigation shows that the physicians in northern Sweden have a fairly good knowledge about the existing rules for reporting ADRs in Sweden. However, the attitudes leave room for considerable under-reporting due to matters related mainly to the medical impact of the reaction and of reporting it, but also to the scientific "paradox" of reporting only on suspicion and of course due to lack of time in the health care setting. PMID- 11214785 TI - Detecting drug-drug interactions using a database for spontaneous adverse drug reactions: an example with diuretics and non-steroidal anti-inflammatory drugs. AB - OBJECTIVE: Drug-drug interactions are relatively rarely reported to spontaneous reporting systems (SRSs) for adverse drug reactions. For this reason, the traditional approach for analysing SRS has major limitations for the detection of drug-drug interactions. We developed a method that may enable signalling of these possible interactions, which are often not explicitly reported, utilising reports of adverse drug reactions in data sets of SRS. As an example, the influence of concomitant use of diuretics and non-steroidal anti-inflammatory drugs (NSAIDs) on symptoms indicating a decreased efficacy of diuretics was examined using reports received by the Netherlands Pharmacovigilance Foundation Lareb. METHODS: Reports received between 1 January 1990 and 1 January 1999 of patients older than 50 years were included in the study. Cases were defined as reports with symptoms indicating a decreased efficacy of diuretics, non-cases as all other reports. Exposure categories were the use of NSAIDs or diuretics versus the use of neither of these drugs. The influence of the combined use of both drugs was examined using logistic regression analysis. RESULTS: The odds ratio of the statistical interaction term of the combined use of both drugs was increased [adjusted odds ratio 2.0, 95% confidence interval (CI) 1.1-3.7], which may indicate an enhanced effect of concomitant drug use. CONCLUSION: The findings illustrate that spontaneous reporting systems have a potential for signal detection and the analysis of possible drug-drug interactions. The method described may enable a more active approach in the detection of drug-drug interactions after marketing. PMID- 11214786 TI - Predictors for prophylactic antithrombotic prescribing in ischaemic heart disease and the impact of national guidelines. AB - OBJECTIVES: Assessment of predictors for initiating prophylactic antithrombotic prescribing for patients newly diagnosed with ischaemic heart disease (IHD) and the impact of the introduction of national guidelines. DESIGN AND SETTING: A retrospective case-control study was performed using pharmacy prescription data from 120,000 Dutch patients over a 5-year period. IHD patients were identified using as a marker multiple nitrate prescriptions [anatomical-chemical-therapeutic (ATC) code CO1D] indicating chronic use. Initiation of antithrombotic therapy was likewise identified using ATC codes B01AA and B01AC (oral anticoagulants and thrombocyte aggregation inhibitors), prescribed within 6 months following the first nitrate prescription. Statistically significant (P<0.05) predictors were assessed using multivariable analysis considering patient, prescriber and medication characteristics. RESULTS: Of the 2598 patients who met specified inclusion criteria for newly diagnosed IHD, approximately 35% was not prescribed any type of antithrombotic therapy. Male patients [odds ratio (OR) 2.4, 95% confidence interval (CI) 2.0-2.9], patients with cardiovascular (other than IHD) and diabetic co-morbidity (OR 6.4, 95% CI 4.8-7.9 and OR 1.6, 95% CI 1.1-2.1, respectively) and patients using isosorbide mononitrate rather than isosorbide dinitrate as anti-ischaemic main therapy (OR 2.1, 95% CI 1.3-2.5) were most likely to be prescribed antithrombotic therapy. Furthermore, initiating antithrombotic prescribing was more likely after the introduction of national guidelines (OR 1.4, 95% CI 1.1-1.7). CONCLUSIONS: Initiating antithrombotic prescribing in newly diagnosed IHD patients can be predicted by patient gender, certain co-morbidity and main type of nitrate therapy. The introduction of national guidelines has resulted in an increase of prophylactic antithrombotic prescribing in accordance with their contents. PMID- 11214787 TI - Influence of physician's education, drug information and medical-care settings on the quality of drugs prescribed. AB - OBJECTIVE: To identify factors associated with low prescription quality in primary care. METHODS: We carried out a cross-sectional study on a sample of 405 primary care physicians in Galicia (Northwest Spain). The following independent variables were collected through a mail questionnaire survey: physician's education and speciality, physician's perception of the quality of available drug information sources, type of practice and number of patients. We constructed multiple regression models using as dependent variables four indicators of the quality of drugs prescribed. RESULTS: The response rate was 75.2%. The quality of drugs prescribed was found to be associated with regulated physician training (P = 0.001), perceived credibility of information sources (P = 0.013) and environmental characteristics of the practice (reform model and number of patients' cards). CONCLUSION: Study results suggest that in order to improve the quality of drugs prescribed, physician education and training must be improved and the role of pharmaceutical companies in physician training should be limited, emphasising more objective sources of information, such as therapeutic guidelines. Our results also underline the need to complete the reform of our primary care system and promote better relationships among physicians and between physicians and patients. PMID- 11214788 TI - A study of drug utilisation and cost of treatment in patients hospitalised with unstable angina. AB - OBJECTIVE: The current study was designed to investigate drug utilisation in the management of unstable angina in India and to calculate the costs incurred by patients in the treatment of a single episode of unstable angina. METHODS: We conducted a prescription survey to examine the use of antianginal drugs in patients with unstable angina in a tertiary care Indian hospital. The use of concurrent medications such as antidiabetic, antihypertensive and lipid-lowering agents was also examined. Data on the cost of treatment, investigations, income, and family size were collected from the case histories or direct interviews with the patients/relatives. RESULTS: A total of 336 consecutive prescriptions were evaluated. Aspirin was the most frequently prescribed drug (98%) followed by nitroglycerin infusion (90%) and enoxaparin (52%). One of the heparins was used by 89% of all patients and beta-blockers by up to 62% of the patients. Besides antianginals, antihypertensive (49%) and antidiabetic (16%) drugs were commonly coadministered. The mean (+/- SD) cost of treatment of a single episode of unstable angina in the hospital was US $494 (+/- 271) against an annual per capita income of US $245. The mean (+/- SD) cost incurred by the patients due to drugs alone during the hospital stay was US $70 (+/- 18) and enoxaparin accounted for 60% of the expenditure due to drugs. CONCLUSIONS: The results of our study show that low-molecular-weight heparin, enoxaparin, is replacing unfractionated heparin in the treatment of unstable angina. In view of the use of costly new drugs, there is an urgent need for carrying out pharmacoeconomic analysis in developing countries as the treatment of a single episode of unstable angina imparts a considerable economic burden on the patient. PMID- 11214789 TI - Agranulocytosis associated with calcium dobesilate clinical course and risk estimation with the case-control and the case-population approaches. AB - OBJECTIVE: Calcium dobesilate is used in the treatment of diabetic retinopathy, chronic venous insufficiency, haemorrhoids and other ill-defined vascular conditions. It has been associated with agranulocytosis in anecdotal reports. We describe the clinical course of a series of patients who developed agranulocytosis while taking this drug, and we estimate the risk by means of both a case-control and a case-population strategy. METHODS: All cases of agranulocytosis meeting strict predefined diagnostic criteria in an area of 3.3 to 3.9 x 106 inhabitants in the period 1980-1998 were identified. Cases and age-, gender- and hospital-matched controls were interviewed with a structured questionnaire including a detailed drug history. Each case was reviewed and confirmed by a haematologist, who was blind with respect to drug exposures. Consumption data were used to estimate the risk of agranulocytosis associated with calcium dobesilate using a case-population approach in which the incidence of agranulocytosis among users of calcium dobesilate was compared with that among the non-exposed population. RESULTS: After a follow up of 68.55 x 10(6) person years, 345 cases of agranulocytosis (242 community cases) were assembled. Reliable information was obtained from 216 cases. Two patients exhibited positive rechallenge. Twelve cases (5.6%) and 5 of 1380 controls (0.4%) had taken calcium dobesilate in the week before. With the case-control approach, the odds ratio was 23.66 [95% confidence interval (CI), 7.54-74.24], the attributable risk was 5.3% (95% CI, 3.0-9.4), and the number of cases attributable to dobesilate in the study area during the study period was 12.8. The case-population estimates were an incidence of 121.03 cases per 10(6) patient-years, a relative risk of 39.55 (95% CI, 17.96-77.49), an attributable risk of 6.73% (CI 3.4-12.9), and 16.30 cases attributable to dobesilate in the study area during the study period. DISCUSSION: This study adds to evidence indicating that the case-population method is adequate for the study of rare type B adverse drug reactions. An additional advantage of this approach is that the incidence of the disease of interest among those exposed to the drug can be estimated. The risk of agranulocytosis associated with calcium dobesilate should be considered in relation to poor evidence of its clinical efficacy. PMID- 11214790 TI - Candesartan and acute liver injury. PMID- 11214792 TI - Microbiology of the 'G-bacteria' in activated sludge. AB - This review discusses a group of bacteria, the 'G-bacteria', which have a distinctive morphology of cocci in tetrads, sheets or clusters, that are seen in large numbers in many activated sludge biomass samples. Isolates of 'G-bacteria' that have been grown axenically are phylogenetically diverse. The Gram-negative members include several alpha- and beta-proteobacteria, among which is the genus Amaricoccus, while the Gram-positive 'G-bacteria' contain several members of the actinobacteria. It is probable that other, as yet uncharacterized, 'G-bacteria' exist in activated sludge. The hypothesis that these 'G-bacteria' are detrimental to the process of enhanced biological phosphate removal by competing for substrates anaerobically with the phosphate-accumulating bacteria in such systems, based as it is largely on mixed-culture studies, receives little support from studies using those available in pure culture. The evidence on which these conclusions are founded is discussed, as are the arguments used to explain why these 'G-bacteria' all appear to thrive under conditions found in certain activated sludge systems. PMID- 11214791 TI - Prolonged sedation due to an accumulation of midazolam in an intensive care patient with hypothyroidism. PMID- 11214793 TI - Population genetics of Escherichia coli in a natural population of native Australian rats. AB - Escherichia coli, a normal inhabitant of the intestinal tract of mammals and birds, is a diverse species. Most studies on E. coli populations involve organisms from humans or human-associated animals. In this study, we undertook a survey of E. coli from native Australian mammals, predominantly Rattus tunneyi, living in a relatively pristine environment in the Bundjalung National Park. The genetic diversity was assessed and compared by multilocus enzyme electrophoresis (MLEE), sequence analysis of the mdh (malate dehydrogenase) gene and biotyping using seven sugars. Ninety-nine electrophoretic types were identified from the 242 isolates analysed by MLEE and 15 sequences from the mdh genes sequenced from 21 representative strains. The Bundjalung isolates extend the diversity represented by the E. coli reference (ECOR) set, with new MLEE alleles found in six out of 10 loci. Many of the Bundjalung isolates fell into a discrete group in MLEE. Other Bundjalung strains fell into the recognized E. coli ECOR set groups, but tended to be at the base of both the MLEE and mdh gene trees, implying that these strains are derived independently from ancestral forms of the ECOR groups and that ECOR strains represent only a subset of E. coli adapted to humans and human-associated animals. Linkage disequilibrium analysis showed that the Bundjalung population has an 'epidemic' population structure. The Bundjalung isolates were able to utilize more sugars than the ECOR strains, suggesting that diet plays a prominent role in adaptation of E. coli. PMID- 11214794 TI - Isolation and characterization of a chromium-reducing bacterium from a chromated copper arsenate-contaminated site. AB - A Gram-negative bacterium (CRB5) was isolated from a chromium-contaminated site that was capable of reducing hexavalent chromium to an insoluble precipitate, thereby removing this toxic chromium species from solution. Analysis of the 16S rRNA from the isolate revealed that it was a pseudomonad with high similarity to Pseudomaonas synxantha. CRB5 was tolerant to high concentrations of chromate (500 mg l(-1)) and can reduce Cr(VI) under aerobic and anaerobic conditions. It also exhibited a broad range of reduction efficiencies under minimal nutrient conditions at temperatures between 4 degrees C and 37 degrees C and at pH levels from 4 to 9. As reduction increased, so did total cellular protein, indicating that cell growth was a requirement for reduction. Under low nutrient conditions with CRB5 or when using non-sterile contaminated groundwater from the site, reduction of Cr(VI) was followed by a increase in solution turbidity as a result of the formation of fine-grained Cr(III) precipitates, most probably chromium hydroxide mineral phases such as Cr(OH)3. Chromium adsorption and precipitation, as observed by transmission electron microscopy coupled with energy dispersive X ray spectroscopy (TEM/EDS), revealed that the surfaces of the cells were uniformly stained with bound Cr(III) and amorphous precipitates (as determined by selected area electron diffraction; SAED). A mass balance of chromium in a batch bioreactor revealed that up to 30% of the total Cr was as settable precipitates or bound to cells. PMID- 11214795 TI - Variations in antibiotic resistance profile in Enterobacteriaceae isolated from wild Australian mammals. AB - We carried out a retrospective analysis of 946 strains of Enterobacteriaceae isolated from wild Australian mammals between 1993 and 1997. The prevalence of resistance to fixed concentrations of 32 antimicrobial agents was determined, and the respective roles that taxonomic family of the host, state of origin and bacterial species play in defining prevalence and range of resistance were investigated. Our results demonstrated a low but widespread prevalence of antimicrobial resistance in wild isolates. Only amikacin, ciprofloxacin, meropenem and gentamicin inhibited growth in all 946 samples. There was extensive variation in the combination of antibiotics to which isolates were resistant, and multiple antibiotic resistance was common. Geographical location and host group significantly influenced the antibiotic resistance profile of an isolate, whereas bacterial species influenced both the resistance profile of an isolate and the number of antibiotics it was resistant to. The role of these factors in determining observed antibiotic resistance profiles suggests that any study measuring resistance in wild isolates should include the broadest possible range of bacterial species, host species and sampling locations. As such, this study provides an important new baseline for future measurements of antibiotic resistance in the Australian environment. PMID- 11214796 TI - Comparison of microbial populations in model and natural rumens using 16S ribosomal RNA-targeted probes. AB - A model rumen system, dual-flow continuous culture fermenters, was evaluated by two comparative criteria in two experiments using ribosomal (r)RNA-targeted DNA probes to compare key microbial groups in samples. The initial experiment measured temporal changes in population structure during adaptation of ruminal microbial populations in fermenters over 240 h. The fermenter inoculum contained 34.9% Bacteria, 60.1% Eukarya and 6.8% Archaea measured as a fraction of total small subunit (SSU) rRNA quantified using a universal probe. The cellulolytic bacterial genus Fibrobacter comprised 9.5% of total SSU rRNA in the inoculum. After 240 h of fermenter operation, the average abundance was 80.9% Bacteria, 6.1% Eukarya, 5.1% Archaea and Fibrobacter genus accounted for 6.6% of the total SSU rRNA. Divergence between ruminal and fermenter population structure was evaluated in the second experiment and samples were classified as ruminal, inoculum or fermenter (96, 120, 144 and 168 h of fermenter operation). Fermenter samples had higher relative abundances of Bacteria (84.5%) and Archaea (2.1%) and lower relative abundances of Eukarya (1.8%) than ruminal samples (average 48.0% Bacteria, 1.3% Archaea and 61.5% Eukarya). The relative abundance of Fibrobacter was similar in all samples, averaging 2.5%. The ruminal and fermenter samples had similar proportions of F. succinogenes and F. succinogenes subgroup 3 (as a percentage of Fibrobacter SSU rRNA). Fibrobacter succinogenes subgroup 1 and F. intestinalis proportions of Fibrobacter were lower in fermenter samples (8.2% and 0.7% respectively) than in ruminal samples (28.4% and 2.2% respectively). Fermenters were able to maintain a core prokaryotic community structure similar to the native microbial community in the rumen. Although protozoa populations were lost, maintenance of Fibrobacter and archaeal populations indicated that the model system supported a functional community structure similar to the rumen. This model rumen system may serve as a suitable tool for studying aspects of ruminal microbial ecology and may resolve some of the relationships between microbial community structure and function by providing control of experimental conditions. PMID- 11214797 TI - Novel forms of ring-hydroxylating dioxygenases are widespread in pristine and contaminated soils. AB - Ring-hydroxylating dioxygenases (RHDs) are of central importance to bacterial recycling of aromatic hydrocarbons, including anthropogenic pollutants. The database of presently characterized RHDs is biased towards those from organisms readily isolated on anthropogenic substrates. To investigate the extent to which RHDs from extant organisms reflect the natural diversity of these enzymes, we developed a polymerase chain reaction (PCR) method for retrieval of RHD gene fragments from environmental samples. Gene libraries from two contaminated and two pristine soil samples were constructed. None of the inferred peptides from clones examined were identical to previously described RHDs; however, all showed significant sequence homology and contained key catalytic residues. On the basis of sequence identity, the environmental clones clustered into six distinct groups, only one of which included known RHDs. One of the new sequence groupings was particularly widespread, being recovered from all soil samples tested. Comparison of inferred peptide sequences of the environmental clones and known RHDs showed the former to have greater sequence variation at sites thought to influence accessibility of the active site than that seen between currently known RHDs. We conclude that presently characterized RHDs do not adequately represent the diversity of function found in in situ forms. PMID- 11214798 TI - Bacterial chromosomal painting for in situ monitoring of cultured marine bacteria. AB - We previously described a new method, bacterial chromosomal painting (BCP), for the in situ identification of bacterial cells. Here, we describe the application of this technique to study the ecology and physiology of cultured marine pelagic bacteria from the western Sargasso Sea (WSS). A total of 86 bacteria were isolated from seawater collected from near the surface, at a depth of 250 m and from nutrient-amended seawater incubations. The 10 bacterial isolates that were best represented in environmental genomic DNA from the WSS were selected using reverse genome probing. BCP hybridization cell counts were used to determine the depth-specific distribution of one of the alpha proteobacterial isolates, B5-6, in the WSS during two thermal stratification regimes: stratified and partially mixed. The maximum cell count measured for B5-6 at the summer deep chlorophyll maximum was approximately 4% of the total cell count. This study is the first application of BCP to natural environments. PMID- 11214799 TI - Effects of O2 and CH4 on presence and activity of the indigenous methanotrophic community in rice field soil. AB - The activity and distribution of methanotrophs in soil depend on the availability of CH4 and O2. Therefore, we investigated the activity and structure of the methanotrophic community in rice field soil under four factorial combinations of high and low CH4 and O2 concentrations. The methanotrophic population structure was resolved by denaturant gradient gel electrophoresis (DGGE) with different PCR primer sets targeting the 16S rRNA gene, and two functional genes coding for key enzymes in methanotrophs, i.e. the particulate methane monooxygenase (pmoA) and the methanol dehydrogenase (mxaF). Changes in the biomass of type I and II methanotrophic bacteria in the rice soil were determined by analysis of phospholipid-ester-linked fatty acid (PLFA) biomarkers. The relative contribution of type I and II methanotrophs to the measured methane oxidation activity was determined by labelling of soil samples with 14CH4 followed by analysis of [14C] PLFAs. CH4 oxidation was repressed by high O2 (20.5%), and enhanced by low O2 (1%). Depending on the CH4 and O2 mixing ratios, different methanotrophic communities developed with a higher diversity at low than at high CH4 concentration as revealed by PCR-DGGE. However, a prevalence of type I or II populations was not detected. The [14C]-PLFA fingerprints, on the other hand, revealed that CH4 oxidation activity was dominated by type I methanotrophs in incubations with low CH4 mixing ratios (1000 p.p.m.v.) and during initiation of CH4 consumption regardless of O2 or CH4 mixing ratio. At high methane mixing ratios (10 000 p.p.m.v.), type I and II methanotrophs contributed equally to the measured CH4 metabolism. Collectively, type I methanotrophs responded fast and with pronounced shifts in population structure and dominated the activity under all four gas mixtures. Type II methanotrophs, on the other hand, although apparently more abundant, always present and showing a largely stable population structure, became active later and contributed to CH4 oxidation activity mainly under high CH4 mixing ratios. PMID- 11214800 TI - Microenvironments and distribution of nitrifying bacteria in a membrane-bound biofilm. AB - The distribution of nitrifying bacteria of the genera Nitrosomonas, Nitrosospira, Nitrobacter and Nitrospira was investigated in a membrane-bound biofilm system with opposed supply of oxygen and ammonium. Gradients of oxygen, pH, nitrite and nitrate were determined by means of microsensors while the nitrifying populations along these gradients were identified and quantified using fluorescence in situ hybridization (FISH) in combination with confocal laser scanning microscopy. The oxic part of the biofilm which was subjected to high ammonium and nitrite concentrations was dominated by Nitrosomonas europaea-like ammonia oxidizers and by members of the genus Nitrobacter. Cell numbers of Nitrosospira sp. were 1-2 orders of magnitude lower than those of N. europaea. Nitrospira sp. were virtually absent in this part of the biofilm, whereas they were most abundant at the oxic-anoxic interface. In the totally anoxic part of the biofilm, cell numbers of all nitrifiers were relatively low. These observations support the hypothesis that N. europaea and Nitrobacter sp. can out-compete Nitrosospira and Nitrospira spp. at high substrate and oxygen concentrations. Additionally, they suggest microaerophilic behaviour of yet uncultured Nitrospira sp. as a factor of its environmental competitiveness. PMID- 11214802 TI - Antigen 43 facilitates formation of multispecies biofilms. AB - Antigen 43 (Ag43) is a surface-displayed autotransporter protein of Escherichia coli. By virtue of its self-association characteristics, this protein is able to mediate autoaggregation of E. coli cells in static cultures. Here, we show that Ag43 can be expressed in a functional form on the surface of Pseudomonas fluorescens. Ag43 expression dramatically enhances the biofilm-forming potential of both E. coli and P. fluorescens to abiotic surfaces in simple microtitre well assays and in flow chambers. Importantly, Ag43-expressing E. coli and P. fluorescens cells tagged with Gfp and Rfp were shown to form interwoven biofilms in flow chambers. The three-dimensional structures of the biofilms were analysed by laser-confocal microscopy. Heterogeneous expression of Ag43 induced interspecies cell-to-cell contact that generated multispecies biofilm formation. Our data indicate that this versatile molecular tool can be used for the rational design of multispecies biofilms. More specifically, this novel technology offers opportunities for the design of multispecies consortia in which the concerted action of several bacterial species is required, e.g. waste treatment and degradation of pollutants. PMID- 11214801 TI - Enhancing desulphurization by engineering a flavin reductase-encoding gene cassette in recombinant biocatalysts. AB - Biological desulphurization of petroleum feedstocks and products may offer an attractive alternative to reduce sulphur oxide emissions that cause serious environmental pollution. Dibenzothiophene (DBT) desulphurization via the Dsz pathway of Rhodococcus erythropolis IGTS8 is an energetically expensive process that consumes reducing equivalents. We have shown in this work that the HpaC oxidoreductase from Escherichia coli W is able to supply the required FMNH2 to the Dsz monooxygenases. The cloning and expression of the hpaC gene in Pseudomonas strains bearing the dszABC gene cluster significantly enhanced DBT desulphurization efficacy of the recombinant biocatalysts in a resting-cell process, thus indicating that overexpression of a heterologous flavin reductase in the host cell is critical for a high rate of sulphur removal in vivo. The hpaC and dszABC genes have been engineered as a single transcription unit under control of broadhost-range regulatory signals in a mobilizable DNA cassette that can be used to confer a DBT desulphurization phenotype to a wide variety of bacteria regardless of the expression of putative housekeeping flavin reductases within the host cells. This cassette will be very useful in exploring the biotechnological potential of novel biocatalysts for developing an efficient desulphurization process. PMID- 11214803 TI - Monitoring of Desulfitobacterium frappieri PCP-1 in pentachlorophenol-degrading anaerobic soil slurry reactors. AB - Anaerobic biodegradation of pentachlorophenol (PCP) was studied in rotative bioreactors containing 200 g of PCP-contaminated soil and 250 ml of liquid medium. Reactors were bioaugmented with cells of Desulfitobacterium frappieri strain PCP-1, a bacterium able to dehalogenate PCP to 3-chlorophenol. Cells of strain PCP-1 were detected by quantitative PCR for at least 21 days in reactors containing 500 mg of PCP per kg of soil but disappeared after 21 days in reactors with 750 mg of PCP per kg of soil. Generally, PCP was completely removed in less than 9 days in soils contaminated with 189 mg of PCP per kg of soil. Sorption of PCP to soil organic matter reduced its toxicity and enhanced the survival of strain PCP-1. In some non-inoculated reactors, the indigenous microorganisms of some soils were also able to degrade PCP. These results suggest that anaerobic dechlorination of PCP in soils by indigenous PCP-degrading bacteria, or after augmentation with D. frappieri PCP-1, should be possible in situ and ex situ when the conditions are favourable for the survival of the degrading microorganisms. PMID- 11214804 TI - Web alert. Thermophilic bacteria. PMID- 11214805 TI - Sample selection bias, is misleading. PMID- 11214806 TI - Treatment practices for childhood posttraumatic stress disorder. AB - OBJECTIVE: This study surveyed practices in treating childhood PTSD among child psychiatrists and non-M.D. therapists with self-identified interest in treating traumatized children. METHOD: An anonymous survey was mailed to 207 child psychiatrists ("medical") and 460 nonphysician ("non-medical") therapists inquiring about current interventions used to treat children with PTSD. RESULTS: Two hundred and forty-seven responses were received: of 77 medical and 82 nonmedical respondents who currently treat children with PTSD, a wide variety of modalities are used. Most preferred modalities among medical responders were pharmacotherapy, psychodynamic, and cognitive-behavioral therapy. Most preferred modalities among nonmedical respondents were cognitive-behavioral, family, and nondirective play therapy. Ninety-five percent of medical respondents used pharmacotherapy for this disorder; most preferred medications to treat childhood PTSD were selective serotonin reuptake inhibitors and alpha-adrenergic agonists. Several significant differences between medical and nonmedical practices were identified. CONCLUSIONS: There is little clinical consensus regarding the effectiveness of the many modalities used to treat traumatized children who have PTSD symptoms; empirical research is particularly needed to evaluate the efficacy of pharmacotherapy and EMDR. PMID- 11214807 TI - Play and social skills in maltreated and non-maltreated preschoolers during peer interactions. AB - OBJECTIVE: The goal of the study was to investigate whether maltreated children differ from nonmaltreated children with regard to their social skills and play behaviors. METHOD: The social skills and free-play behaviors of 30 3- to 5-year old maltreated and nonmaltreated children were compared. Fifteen children with a range of maltreatment experiences drawn from a hospital-based therapeutic nursery treatment program and 15 demographically similar children drawn from a home-based Head Start program participated in the study. All children were of low socioeconomic status. Children's free-play peer interactions were videotaped during the first 3 months of attendance in either program and analyzed along social and cognitive dimensions. Teachers and therapists rated children's social skills in peer interactions. RESULTS: Maltreated children were found to have significantly poorer skill in initiating interactions with peers and maintaining self-control, as well as a greater number of problem behaviors. Significant differences were not found between groups with regard to social participation or cognitive level of play. Significant correlations of moderate strength were found between social participation in play and social skills for the sample as a whole: total social skills score was positively related to interactive play, and negatively related to solitary play. CONCLUSION: The results suggest that the experience of maltreatment has a negative impact on children's developing interpersonal skills above and beyond the influence of factors associated with low socioeconomic status and other environmental stressors. PMID- 11214808 TI - Childhood sexual abuse, adolescent sexual coercion and sexually transmitted infection acquisition among homeless female adolescents. AB - OBJECTIVE: To examine the relationship between childhood experiences of sexual abuse, sexual coercion during adolescence, and the acquisition of sexually transmitted infections (STIs) in a population of homeless adolescents. METHOD: Homeless adolescent females (N = 216) from a northwestern United States city were recruited by street outreach workers for a longitudinal study of STI epidemiology. Baseline data on childhood abuse and recent history of sexual coercion were used to predict physiologically confirmed STI acquisition over the subsequent 6 months. RESULTS: About 38% of all girls reported a history of childhood sexual abuse (CSA). Girls with a history of CSA were more likely to report recent sexual coercion. In turn, sexual coercion in the last three months was significantly associated with a higher number of sexual partners (but not with a greater frequency of intercourse or with lower rates of condom use). Number of sexual partners significantly predicted the future acquisition of an STI within 6 months. CONCLUSIONS: Interventions to reduce risky sexual behaviors in homeless adolescent females may need to consider the impact of CSA, particularly on the number of sexual partners during adolescence. However, it also should be noted that engagement in intercourse often results from coercion and is not voluntary in this population. PMID- 11214809 TI - Examining child sexual abuse evaluations: the types of information affecting expert judgment. AB - OBJECTIVE: There were two aims: First, to determine to what extent four variables, disclosure, doll play, affect and collateral information, affect the decision-making processes of child sexual abuse experts and lay persons when confronted with an abuse allegation, and second, to see how these two groups of raters might differ from one another. METHOD: A randomized block partially confounded factorial design was used. Participants made abuse likelihood and confidence ratings in response to six hypothetical cases of child sexual abuse, four of which had varying combinations of the four types of information and two of which were constant across all raters. Participants also completed attitudes and knowledge questionnaires. RESULTS: Disclosure and collateral information both had large effects on both rater groups. Doll play and affect had little or no effect on the decisions of either group. Experts were slightly more conservative in their judgments over all than students were. Experts also displayed more knowledge of the sexual abuse literature and more child-believing attitudes than their student counterparts. CONCLUSION: Concrete information such as disclosure statements and collateral information affected abuse decisions while inferential data such as doll play and affect did not. The goal of these evaluations may be the clarification of such concrete information and the inferential data may be used only to guide one's inquiry. This conclusion argues against the concern that experts might jump to conclusions of abuse merely based upon suggestive, symbolic material. PMID- 11214810 TI - Factors predicting PTSD, depression, and dissociative severity in female treatment-seeking childhood sexual abuse survivors. AB - OBJECTIVE: Two main questions were asked: (1) what abuse characteristics relate to PTSD, depressive, and dissociative severity in adult survivors of child sexual abuse (CSA); and (2) what abuse characteristics influence the severity of dissociation during CSA. METHOD: 89 female CSA survivors' current symptoms of PTSD, depression, and dissociation were assessed with standardized measures. Additionally, abuse characteristics (e.g., age of onset, peritraumatic dissociation) were assessed with a structured interview. RESULTS: Correlational analyses indicated that peritraumatic dissociation was most strongly related to all three types of symptom severity. Additional posthoc correlational analyses revealed that women who experienced penile penetration, believed someone/thing else would be killed, and/or were injured as a result of the abuse exhibited more severe peritraumatic dissociation. Regression analyses indicated that peritraumatic dissociation was the only variable to significantly predict symptom severity across symptom type or disorder. Furthermore, different abuse characteristics predicted adult symptom severity and peritraumatic dissociation. CONCLUSIONS: The relation between peritraumatic dissociation and adult symptomatology was most intriguing and has two main clinical implications: (1) teaching engagement strategies to some CSA survivors in hopes of containing dissociative symptoms immediately following the abuse and (2) the inclusion of exposure-based interventions in the treatment of some adult CSA survivors where indicated. PMID- 11214811 TI - Perceived and actual academic competence in maltreated children. AB - OBJECTIVE: The aims were twofold: 1) to determine whether maltreated and nonmaltreated children differed in the accuracy of their self-assessments of academic achievement; and 2) to determine whether discrepancies between perceived and actual academic competence were related to perceptions of social support from mothers, teachers, and peers. METHOD: A sample of 195 maltreated children known to a state protective service agency was compared to a control group of 179 nonmaltreated children. The groups were matched on child's gender, age, ethnicity, and birth order; socioeconomic ranking of neighborhood; and family structure. RESULTS: Although maltreated children had significantly lower achievement scores than did nonmal-treated children, the two groups did not differ on perceived academic competence. With regard to discrepancies between perceived and actual competence, maltreated children were more likely than nonmaltreated children to overestimate their level of competence, particularly for reading and arithmetic. Overall, children who reported low maternal support were more likely to overestimate reading competence than were those who reported average or high maternal support. When maltreatment status was considered, maltreated children with low support seemed likely to overestimate abilities, whereas nonmaltreated children with low support seemed likely to underestimate competence. CONCLUSIONS: Maltreated children may overestimate their academic abilities in order to compensate for self-perceptions of low self-worth. Efforts to improve academic performance in maltreated children should focus not only on increasing academic skills but also on enhancing self-esteem. PMID- 11214812 TI - Parental features and quality of life in the decision to remove children at risk from home. AB - OBJECTIVES: The study examined the associations between the decisions of child protection officers to remove children at risk from home and a) the features of the children's parents and b) the quality of life the parents make it possible for their children to have. METHOD: 194 child protection workers completed a parental features questionnaire, child injury questionnaire, and Shye's Systemic Quality of Life Questionnaire on two children, one removed from home, the other remained. RESULTS: Parental cooperation with the worker, relationship with the child, addiction, and cleanliness were related to both the decision and the assessment of enabling quality of life. Parents' poverty, criminality, psychological problems, and cognitive impairment were related only to the workers assessment of parents enabling quality of life. Family status was related only to the decision. While injury to the child was associated with the decision, it added virtually nothing to the explanation of the decision beyond parental features and enabling. CONCLUSIONS: The variables related to the workers' assessment of the parents' enabling overlapped only partially with those related to the decision. The parents' features and enabling made only a modest contribution to explaining the workers' decisions. The findings suggest that the quality of life measure used in this study encompasses injury. PMID- 11214813 TI - Patterns of interactions in multidisciplinary child protection teams in New Jersey. AB - OBJECTIVE: The objective of this study was to gain an understanding of how multidisciplinary team members in child protection worked together within the team, meeting to provide assessments of, and services to, children and families. METHOD: Fifteen multidisciplinary child-protection teams in New Jersey were observed during one meeting of each team. The interaction among team members was recorded and analyzed using a structured observation method, Bales' Interaction Process Analysis. RESULTS: There was a wide variation in participation among team members, with some contributing nothing to the meeting and others contributing a great deal. In some teams, participation by members was more equal than others. Some professional groups and agencies contributed very little to any meeting while others contributed a great deal to many meetings. CONCLUSIONS: Professionals are members of multidisciplinary teams because they are expected to contribute to the investigation of child maltreatment cases and to the planning for further work with cases. However, the findings from this study suggest that there is a considerable degree of inequality in levels of participation in multidisciplinary meetings. It is particularly noticeable that staff from the prosecutor's offices participate in every meeting and either the agency as a whole or individual members of it dominate many of the meetings. PMID- 11214814 TI - Sample selection bias and racial differences in child abuse reporting: once again. PMID- 11214815 TI - Child abuse reporting: teachers' perceived deterrents. AB - OBJECTIVE: There are three general objectives: First, to determine the number of reports of abuse made by teachers, their knowledge of child abuse laws and reporting procedures, and their perceived deterrents in reporting abuse; second, to determine if there were gender or ethnic differences in reporting; and third, to evaluate teachers responses to case vignettes. METHOD: A survey of 197 teachers was conducted. They were given a questionnaire that included demographic information, knowledge of child abuse laws and procedures, and two scenarios of legally reportable child abuse. RESULTS: Seventy-three percent of this sample reported that they had never made a report of child abuse, while those who had made reports made an average of one report. Only 11% of teachers reported that there were instances in which they believed abuse may have occurred, but failed to report. Additionally, these teachers felt that their pre- and post-service training did not adequately prepare them for abuse reporting. The most common reasons cited for not reporting abuse were fear of making an inaccurate report, feeling as though child protective services do not help families, and no apparent physical signs of abuse. There were no gender differences in reporting. The teachers' responses to the case vignettes were not consistent with their previous reports. CONCLUSIONS: In general, most teachers reported having never made a child abuse report. Although only a small percentage of teachers reported failing to report abuse, when presented with legally reportable case vignettes, many failed to report. The majority of teachers report receiving inadequate training in child abuse signs, symptoms, and reporting procedure. There is an obvious need for more education for teachers that addresses their perceived deterrents and aids them in feeling more confident in making reports of child abuse. PMID- 11214816 TI - Childhood physical abuse, early social support, and risk for maltreatment: current social support as a mediator of risk for child physical abuse. AB - OBJECTIVE: The study investigated whether perceptions of social support in adulthood partially mediated the associations between childhood experiences (i.e., receipt of physical abuse and levels of early social support) and adult risk for child physical abuse. METHOD: Participants included 598 general population adults who completed self-report measures designed to assess childhood physical abuse, perceptions of early and current social support, and risk factors for child physical abuse. Structural equation modeling was used to test and cross validate a model that included the direct effects of child physical abuse and early social support on child physical abuse risk, as well as mediated effects through an influence on adult perceptions of social support. RESULTS: Childhood physical abuse and early social support covaried, such that receipt of physical abuse was associated with lower levels of perceived early social support. Early support, but not child physical abuse, had an indirect effect (i.e., through current support) on child physical abuse risk. More specifically, levels of early support were directly related to adult perceptions of support, and adult perceptions of support were inversely associated with child physical abuse risk. Childhood physical abuse was directly related to child physical abuse risk. CONCLUSIONS: Low levels of early support may impact risk for child physical abuse by affecting perceptions of others as supportive in adulthood. The receipt of physical abuse in childhood, however, does not appear to impact perceptions of support in adulthood. Research is needed to identify additional factors that may explain the association between receipt of physical abuse in childhood and increased risk of child physical abuse in adulthood. PMID- 11214817 TI - Sexual behavioural risks of married men in Oyo State, Nigeria. PMID- 11214818 TI - SM5-1: a new monoclonal antibody which is highly sensitive and specific for melanocytic lesions. AB - Antibodies such as HMB-45 and anti-S100 protein have been widely used as markers of malignant melanoma despite evidence that HMB-45 has a sensitivity of only 67 93% and S100 is nonspecific for melanoma. Using a subtractive immunization protocol in a mouse model of human melanoma, we have generated several monoclonal antibodies with putative specificity for melanoma. After initial screenings, the antibody SM5-1 was chosen because of its intriguing reactivity with melanocytic tumors in both frozen and paraffin sections. The immunohistochemical staining of SM5-1 was studied in paraffin-embedded specimens of 401 melanomas (n = 401; 250 primary melanomas, 151 metastases), melanocytic nevi of the skin (n = 16), nonmelanocytic neoplasms (n = 84). The results were compared with HMB-45 and anti S100 staining. All antibodies reacted with nevi and 97-99% with primary melanomas. Whereas both SM5-1 and anti-S100 stained 96% (146/151) of melanoma metastases, HMB-45 correctly identified only 83% (126/151). All HMB-45-negative metastases were positive for SM5-1. Whereas neither SM5-1 nor HMB-45 stained any of 84 specimens from 40 different nonmelanocytic neoplasms, anti-S100 was positive in 21/84 (25%). While the staining pattern of SM5-1 was mostly homogeneous, small tumor areas in some metastases remained unstained. Staining with SM5-1 was also observed in perivascular dendritic cells, in plasma cells, some myofibroblasts and the secretion of eccrine sweat glands. Nonactivated epidermal melanocytes, keratinocytes, endothelial cells, smooth muscle cells and peripheral nerves were all negative for SM5-1. These results suggest that SM5-1 is highly specific, as well as sensitive, for melanocytic lesions and is useful in the immunohistochemical evaluation of melanoma. PMID- 11214819 TI - Involvement of insulin-like growth factor-I in psoriasis as a paracrine growth factor: dermal fibroblasts play a regulatory role in developing psoriatic lesions. AB - To investigate the contribution of dermal fibroblasts to the development of psoriasis, we examined the expression of mRNA for insulin-like growth factor-I (IGF-I) and its regulator IGF-I binding proteins (IGFBPs) in psoriatic fibroblasts by RT-PCR. We also studied the effect of inflammatory cytokines including interferon gamma (IFN-gamma), tumor necrosis factor alfa (TNF-alpha), and IFN-alpha on the expression of IGF-I and IGFBPs in the fibroblasts. Semiquantitative analysis revealed that IGF-I mRNA expression in psoriatic fibroblasts (PF) was significantly higher than in control fibroblasts (CF). However, no significant difference in IGF-I mRNA was shown between nonlesional psoriatic fibroblasts (NF) and CF. Treatment with IFN-alpha in vitro upregulated IGF-I mRNA in PF and in CF. TNF-alpha appeared to downregulate IGF-I mRNA in PF but had no effect on CF. IFN-gamma did not show a significant effect on IGF-I mRNA levels in any type of fibroblast. IGFBP-3 mRNA was expressed equally in PF and CF, and was not affected by cytokines. The expression of IGFBP-5 mRNA in PF was downregulated by IFN-gamma and TNF-alpha. Taken together, these results indicate that dermal fibroblasts may contribute to the epidermal hyperplasia of psoriasis by promoting keratinocyte proliferation through IGF-I, whose secretion could be modulated by inflammatory cytokines. PMID- 11214820 TI - Role of androgens in female-pattern androgenetic alopecia, either alone or associated with other symptoms of hyperandrogenism. AB - The roles of androgen hypersecretion, in situ enzyme activity, and androgen receptors in androgenetic alopecia in women are still a matter of debate. We studied 187 women with alopecia, which we graded I, II, or III, according to Ludwig's classification, and 21 healthy control women. All participants were subjected to full basal and 1 h post-beta-1-24 corticotropin stimulation endocrine profiles. Abnormal hormone profiles were observed in 67% of the patients with alopecia alone (group A, n = 110) and in 84% of the patients with alopecia plus other symptoms of hyperandrogenism including acne, hirsutism, and menstrual cycle disturbances (group B, n = 77). Mean serum 5alpha-androstane 3alpha,17beta-diol glucuronide (3alpha-AdiolG) levels in all three patient groups (6.50+/-4.10, 8.90+/-5.80, and 14.70+/-8.90 nmol/l, respectively) correlated with the grade of alopecia (I-III) and were significantly higher than in the control group (4.80+/-2.05 nmol/l, P < 0.005). Mean serum sex hormone-binding globulin (SHBG) levels were inversely correlated with the grade of alopecia (I-III) and were significantly lower in all three patient groups (50.55+/-23.50, 40.00+/ 17.65, and 38.80+/-14.10 nmol/l, respectively) than in the control group (61.15+/ 17.65 nmol/l, P < 0.05). Mean serum levels of delta4-androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and 3alpha-AdiolG were higher in group B than in group A, and higher in group A than in the control group. The significant correlations found between adrenal secretion - either positive (with 3alpha-AdiolG levels and the body mass index) or negative (with SHBG levels) - might reflect the important contribution of secretory and metabolic components in the development of alopecia, the severity of which has been shown to be very closely related to observed levels of two of these parameters (3alpha-AdiolG and SHBG). PMID- 11214821 TI - Functional analysis of the stratum corneum of scalp skin: studies in patients with alopecia areata and androgenetic alopecia. AB - Because of the presence of thick long hairs on the scalp, little information is available concerning the functional characteristics of the stratum corneum (SC) of scalp skin. We therefore conducted a functional study of the SC of lesional scalp skin of patients with alopecia areata and of patients with androgenetic alopecia. We compared the scalp with the cheek and the flexor surface of the forearm (volar forearm). The water barrier function of the scalp SC of both patient groups, in terms of transepidermal water loss (TEWL), was almost comparable to that of the volar forearm, and was far better than that of facial skin. However, hydration of the scalp skin surface, as evaluated by measurement of high-frequency conductance, was markedly higher than that of facial skin, and showed significantly higher values than the volar forearm. These characteristics seem to be dependent, at least to some extent, on the amount of sebum-derived skin surface lipids because these were abundant on the scalp skin. Moreover, removal of skin surface lipids led to a significant decrease in skin surface hydration. The superficial corneocytes, the size of which reflects the proliferative activity of the epidermis, were substantially smaller on the scalp than on the volar forearm but significantly larger than on the cheek. These findings suggest that the rate of turnover of the scalp epidermis is intermediate between that of the facial and volar forearm epidermis. We conclude that the SC of the scalp skin in humans is functionally distinct from that of the face and extremities. PMID- 11214822 TI - Biological effects and metabolism of 9-cis-retinoic acid and its metabolite 9,13 di-cis-retinoic acid in HaCaT keratinocytes in vitro: comparison with all-trans retinoic acid. AB - 9-cis-Retinoic acid (9cRA), a geometric isomer of all-trans-retinoic acid (atRA), is an endogenous high-affinity ligand for retinoid X receptors and retinoic acid receptors activating them with high potency. 9,13-di-cis-Retinoic acid (9,13dcRA) has been described as a major plasma metabolite of 9cRA. In this study, the biological activity and the metabolism of 9cRA and 9,13dcRA were investigated and compared with those of atRA in a retinol-free culture system of HaCaT keratinocytes. 9cRA exhibited a slightly weaker activity overall than atRA in inhibiting cell proliferation, inducing cellular retinoic acid binding protein II (CRABP II) mRNA levels and upregulating cytokeratin 19 expression. 9,13dcRA regulated HaCaT keratinocyte activity only at the highest concentration tested (10(-6) M). In cultures of HaCaT keratinocytes with atRA and 9cRA, rapid intracellular accumulation of atRA was observed within 2 h, and atRA levels were higher with atRA treatment than with 9cRA treatment. 9,13dcRA remained relatively stable in the medium with intracellular 9,13dcRA levels below the level of detection. Taken together, 9cRA seems to be slightly less potent than atRA in regulating the biological activity of HaCaT keratinocytes, while its metabolite 9,13dcRA is effectively inactive at biologically relevant concentrations. Our data suggest a prodrug/drug relationship between 9cRA and atRA in human keratinocytes. 9,13dcRA seems to be a weaker prodrug of atRA or an inactive metabolic derivative. PMID- 11214823 TI - N-acetylcysteine downregulates vascular endothelial growth factor production by human keratinocytes in vitro. AB - The present study was designed to evaluate the action of various antioxidants including N-acetylcysteine (NAC) and the flavonoids resveratrol and quercetin on the production of VEGF by human keratinocytes (HKC). NAC, resveratrol, and quercetin dose-dependently suppressed the incorporation of 3H-thymidine into HKC. Values of median inhibitory concentration for NAC, resveratrol, and quercetin were 10 mM, 55 microM, and 15 microM, respectively (P < 0.01). RT-PCR demonstrated VEGF 121 and VEGF 206 expression in all HKC samples. HKC showed baseline expression and a progressive gradual time-dependent increase in VEGF secretion (510+/-75 pg/ml at 24 h), and EGF (2.5-100 ng/ml) enhanced the secretion of VEGF in a dose-dependent fashion. HKC were incubated with NAC (2.5 20 mM) for 2 h prior to the addition of EGF (5 ng/ml) or PMA (10 ng/ml), and a significant decrease (P < 0.01) was found after 24 h of incubation with 2.5 mM NAC. However, neither resveratrol nor quercetin reduced the synthesis of this cytokine. In summary we conclude that NAC and the flavonoid antioxidants resveratrol and quercetin inhibit HKC proliferation regardless of the stage of differentiation and that NAC significantly inhibits VEGF secretion in basal and EGF- or PMA-treated HKC. PMID- 11214824 TI - The patterns of late deterioration in patients with transitional lipomyelomeningocele. AB - INTRODUCTION: Tethering is assumed to be the primary cause of deterioration seen in children with transitional lipomyelomeningocele as they age. The inevitability of deterioration has led to recommendations for prophylactic interventions to stabilize or prevent further clinical deterioration. OBJECTIVE: Determine the frequency and patterns of functional deterioration observed after successful untethering in patients with transitional lipomyelomeningocele and compare functional outcomes with what is known regarding untreated patients. METHODS: Fifty patients having transitional LMMC, treated at a single institution and followed in a multidisciplinary clinic were retrospectively reviewed to determine their clinical status prior to untethering, and the time to development of new symptoms or signs following untethering. RESULTS: 82% of patients were diagnosed and 78% underwent untethering prior to one year of age. All patients had a cutaneous lumbosacral lipoma, 22 patients were considered normal at presentation and 28 showed abnormalities on clinical examination. Forty-nine patients were untethered successfully and all were available for follow-up ranging from 2 to 138 months (mean 39 months). Acute morbidity was limited to transient neurogenic bladder dysfunction and minor wound complications. Late clinical deterioration occurred in the majority of patients. Orthopedic and neurological deterioration occurred over the first 60 months following untethering and urological deterioration occurred thereafter. CONCLUSIONS: Functional loss after untethering is common and the pattern of loss is likely a reflection of the ability to detect abnormalities in this infant population. Untethering does not usually result in permanent acute morbidity, and does not prevent longer-term functional deterioration. The ratio of asymptomatic to symptomatic patients at follow-up in this operative series is similar to age-matched historical series of untreated patients. PMID- 11214825 TI - Prevalence of the Chiari/hydrosyringomyelia complex in adults with spina bifida: preliminary results. AB - AIM: To establish the prevalence of Chiari malformations and hydrocephalus (HS) in adults with spina bifida (SB). INTRODUCTION: Adults with SB have recently been shown to be at risk from significant deterioration arising from the C/HS complex. Little is known about the prevalence of these malformations in adulthood, their natural history, risk factors for deterioration and optimum management. MATERIALS AND METHODS: Patients are recruited from a clinic for adults with SB and hydrocephalus, routinely questioned about recent changes in neurological symptoms and a full neurological examination performed. Functional assessments include: Barthel Index; Nottingham EADL; Nine Hole Peg Test; 10 metre timed walk test. Sagittal T1 and TSE (turbo spin-echo) magnetic resonance images (MRI) of the cranio-cervical junction and spinal cord are obtained using a 1.0-T MRI system with a phased-array surface coil. Scans are reported blindly. RESULTS: 76 patients have been assessed, 40 female, 36 male, mean age 27.5 years. Of these, 48 (63.2%) have symptoms +/- signs compatible with C/HS, but only 18 (23.7%) have reported new, potentially relevant, neurological symptoms over the previous 12 months. Of 25 patients undergoing MRI so far, 19 (76%) have had Chiari malformations and 12 (48%) have had HS. None of those with a negative scan have had signs/symptoms suggestive of the C/HS complex but a negative clinical evaluation has been unable to exclude such pathology. CONCLUSIONS: These early results suggest that the prevalence of the C/HS complex is high in adults with SB and cannot be predicted by neurological examination alone. Given past experience, the need for continued neurological follow up in a large proportion of the SB population throughout adulthood is likely to be essential. PMID- 11214826 TI - Can prognostic indicators be identified in a fetus with an encephalocele? AB - Encephaloceles, like other congenital malformations of the brain diagnosable in utero, can be either complicated (there being an associated chromosomal abnormality, abnormalities in the remainder of the central nervous system (CNS) and/or other organs), or isolated (no abnormalities in the chromosomes, the remainder of the CNS or other organs). Complicated cases invariably have a poor prognosis but amongst those with isolated lesions the outcome is variable with some affected children having poor mental and physical development but others who are only mildly or moderately disabled. To be able to make an informed decision about how to manage their pregnancy parents need to know what the prognosis is likely to be for their fetus with an encephalocele. To see if the necessary information could be reliably gathered by prenatal assessment of affected fetuses, a review was carried out of the medical records and ultrasound scans of 31 fetuses with encephaloceles referred to the Fetal Management Unit at St. Mary's Hospital in Manchester between January 1991 and December 1997. Eighteen of the cohort were classified as having a complicated encephalocele. Thirteen of the pregnancies were terminated; there were three intrauterine deaths, and one neonatal death. There is only one surviving child who is severely disabled. Thirteen fetuses were classified as having isolated encephaloceles, six had a mass of neural tissue in the encephalocele sac and were terminated, one died in utero and six had a cystic lesion or only a nubbin and have survived with few or no abnormalities. This study has shown that it is possible to identify fetuses with an encephalocele with a favourable outcome. PMID- 11214827 TI - Day-care ultrasound avoids urodynamics. AB - BACKGROUND: Post-voiding residual urine is a common problem underlying urinary symptoms in many children often associated with infection. Tertiary referral is often made to exclude a neurological aetiology. This review reports the experience of clinician-performed ultrasound examinations in the Day-Care Unit on 50 children during a 9-month period, with various aetiologies of urinary incontinence avoiding urodynamic studies in 34. METHODS: From March 1999 tertiary referral patients with urinary incontinence with or without infection and secondary referrals not responding to 'standard' management regimes, underwent clinician-performed bladder ultrasound scans in the day-care ward. A standard renal tract ultrasound examination had been reported as normal in 19 patients. In general referral had been made to exclude a neuropathic aetiology. In addition 5 patients were studied who were known to have a neurogenic bladder, 3 with an anorectal anomaly, 3 were post cystoplasty and 2 had undergone surgery for ureteric reflux. RESULTS: In 34 patients it was considered that a urodynamic study had been avoided, while in one results from a urodynamic study were refuted. By means of directly visualising the bladder on real time scanning, 12 children and families achieved a significantly better understanding of the relevance of residual urine in relation to symptoms, or were shown to have normal detrusor function (7), excluding a neuropathic aetiology. The three who had undergone cystoplasty were shown to have adequate bladder volumes in spite of persisting wetness. CONCLUSION: Real-time ultrasound examination of the bladder performed by a clinician in a patient-friendly environment (day-care ward) can provide significant information regarding detrusor function, often avoiding urodynamic studies. The test does not replace formal scanning for anomalies but may provide information that is masked by the more rigid environment of a radiology department, sometimes correcting results from standard urodynamic studies. PMID- 11214828 TI - Decision-making for a successful bowel continence program. AB - Bowel continence is one of the most difficult challenges for patients with spina bifida. Incontinence acts as a social stigma for children and a barrier for adults seeking employment. We present an algorithm for stepwise decision-making in construction of personalized continence programs for greater likelihood of success. The protocol contains 13 assessment points including; stool consistency, frequency and amount; mobility; level of paraplegia: diet; medication; anal/rectal canal tone; prior programs attempted; family routines; age; accessibility; and learning issues. Based on outcomes of these assessments, an individualized bowel program is constructed. The algorithm helps the practitioner and patient decide on components and indicators of a successful continence program. The recommended program might include timed toileting, suppository, continence enema, and ACE procedure, or a combination. Evaluation and patient education address adequate fluid/fiber, appropriate toileting equipment, and use of stool softeners/laxatives. Descriptions are available. Key elements in monitoring a continuing plan for continence include: the degree of constipation and its etiology; changing age; family availability for assistance until interdependence is optimal; wheelchair accessibility of the toilet; and ability to transfer to and from the toilet. Use of the algorithm allows for careful decision-making based on information from the patient and family. This has led to greater success in bowel continence in children with spina bifida. PMID- 11214829 TI - Why do adults with spina bifida and hydrocephalus die? A clinic-based study. AB - AIM: To establish the death rate and factors contributing to death among attenders at a clinic for adults with spina bifida and hydrocephalus (CASBAH). INTRODUCTION: Due to improvements in medical care in the past 40 years, increasing numbers of spina bifida patients go on to prosper in adult life. Despite this, levels of morbidity are high and services for such patients are uneven and unpredictable. MATERIALS AND METHODS: Since 1990 there has been a CASBAH service in Belfast operating on a regional basis. Led by a consultant in rehabilitation medicine, it provides a multidisciplinary approach to patient care. Between 1990 and 1999 there have been 280 referrals to the clinic. Charts were reviewed regarding current health status and mode of death where relevant. RESULTS: There have been 18 deaths during the term of the clinic (6.4%). There were four deaths due to renal failure and two due to cardiac failure. Two deaths occurred following surgery for a Chiari/hydrosyringomyelia complex and one patient died due to shunt malfunction. Three deaths were presumed related to infection. Two deaths were attributable to malignancy (carcinoma of a renal conduit and transitional cell carcinoma of the kidney) and other terminal events in one patient each were: basilar artery aneurysm rupture, post-partum pulmonary embolism, peptic ulcer disease, myocardial infarction and status epilepticus. CONCLUSIONS: Although certain deaths were unpredictable during the period of review and not directly attributable to spina bifida, the majority reflect many of the related secondary health issues of the condition and indicate the need for organised, medically co-ordinated follow-up of adult patients. PMID- 11214830 TI - Longevity of patients born with myelomeningocele. AB - There are limited data concerning the life expectancy for individuals born with myelomeningocele (MM), with and without hydrocephalus. To ascertain such data was our first purpose. We have selected all patients with MM in our computer database, The Patient Data Management System (PDMS/fx). Data were transferred to Excel for primary and SPSS/PC for final analysis by Kaplan-Meier life survival curves. Of the 1,054 patients with MM in the Birth Defects Clinic and the University of Washington Medical Center (UWMC) of Seattle, 505 are now over the age of 21 (391) or have died (114). Follow-up information was available since 1994 for 132, 62% of whom we have had contact within the past 2 years. The second purpose was to identify potential health factors associated with long-term outcome of patients with MM. Patient variables chosen as relevant to survival included hydrocephalus, treatment before or after 1975, and health maintenance determined by outcome for those receiving care within the last 5 years or those last seen before. Age at last appointment and reason for visit were determined in order to identify age-specific health care needs of the adult population. Survival and medical needs were obtained from the UWMC's computer database, Mindscape, and by telephone survey for adult patients not seen in the last 2 years. Death is more frequent earlier in life for those MM patients with hydrocephalus. Ordinary degenerative disorders affect MM patients earlier in life than normals. Our data extend life expectancy for patients with MM and hydrocephalus to age 40 years with some reliability for those treated from 1957 to 1974, but only 24 years for those treated with modern techniques after 1974. More data is needed to determine long-term survival. PMID- 11214831 TI - Beyond multidisciplinary care: a new conceptual model for spina bifida services. AB - Medical care for people who are born with spina bifida (myelodysplasia) is complex and challenging, but the goal of such care is to optimize health and function for people with this condition. Despite years of expert agreement that multidisciplinary care is the medical standard for individuals with spina bifida, this model does not seem to go far enough towards accomplishing the goal of improved function as well as health for all people with spina bifida. Advances in the medical and surgical management of people with spina bifida and society's increased desire to include those with disabilities in family and community life has heightened our expectations for functional/participatory improvement for people with this condition. Some large spina bifida programs have added a separate rehabilitation component to the comprehensive package of services offered to people with spina bifida. The problem with adding further services to the traditional multidisciplinary spina bifida program is the increased complexity and potential for fragmentation that it presents, particularly for the patient and family. We performed a MEDLINE literature search to find information on integrating these services. Although several articles address the importance of either the multidisciplinary spina bifida clinic or a rehabilitation approach, there is little information about integration of medical and rehabilitation services. We propose a new model for spina bifida services throughout the lifespan that integrates the medical and functional/rehabilitative perspectives. Our model for conceptualizing spina bifida services builds on the WHO framework for coding disability (ICIDH-2). This framework includes not only health and functional perspectives, but a participation dimension as well. Furthermore, our new model emphasizes the importance of anticipatory guidance and transitional planning as an integrating dimension applicable across the lifespan. The model is based on three main conceptual dimensions--comprehensiveness, coordination and longitudinality. We are using the model to create standards of care, integrate services and improve their efficiency, and to develop policies regarding spina bifida services. Through this effort we hope to provide better medical and rehabilitation services to those with spina bifida and meet the complex challenge the condition presents throughout the lifespan. PMID- 11214832 TI - Possible role of CSF in a developmental abnormality associated with early-onset hydrocephalus. PMID- 11214833 TI - Early management of meningomyelocele. PMID- 11214834 TI - Suggested goals for intrauterine surgery for the repair of myelomeningoceles. PMID- 11214835 TI - Effect of folic acid fortification in Chile: preliminary results. PMID- 11214836 TI - Infections after cerebrospinal fluid shunting. PMID- 11214837 TI - Growth factor modulation of CSF formation by isolated choroid plexus: FGF-2 vs. TGF-beta1. PMID- 11214838 TI - Percutaneous endoscopic recanalization of catheter. PMID- 11214839 TI - Visual evoked potentials and brainstem auditory evoked potentials in experimental hydrocephalus. PMID- 11214840 TI - Search for the peptide mimics of the antigen produced in ventriculo-peritoneal (VP) shunt infection. PMID- 11214841 TI - The antegrade continence enema (ACE) surgical procedure: patient selection, outcomes, long-term patient management. PMID- 11214842 TI - 44 years experience with management of myelomeningocele: presidential address, Society for Research into Hydrocephalus and Spina Bifida. PMID- 11214843 TI - The ACE procedure--problems behind the success. PMID- 11214844 TI - Self-care skills in young children with myelomeningoceles. PMID- 11214845 TI - The ASPINE study: preliminary results on sex education, relationships and sexual functioning of Dutch adolescents with spina bifida. PMID- 11214846 TI - A community-based model for serving persons with spinal cord disabilities. PMID- 11214847 TI - The study of neural tube defects after the Human Genome Project and folic acid fortification of foods. AB - The implementation of folic acid fortification will eliminate a proportion of neural tube defects (NTD). As a result, the etiologic and clinical profiles of the developmental disorder may both change. In the assessment of NTD as it evolves, the bioinformatics structure and content of the Human Genome Project will find vital application. One important development will be an enhanced understanding of the role of folic acid in global regulation of gene expression through epigenetic processes. In addition, bioinformatics will facilitate coordination of research in the basic sciences with clinical investigations to better define remaining etiologic factors. PMID- 11214848 TI - Service-learning: isn't that what nursing education has always been? PMID- 11214849 TI - Teaching undergraduate nursing research: a narrative review of evaluation studies and a typology for further research. AB - Before knowledge about strategies for teaching undergraduate nursing research can be synthesized, it must be demonstrated that studies evaluating teaching outcomes are valid. A narrative review using Cook and Campbell's validity framework for experimental and quasi-experimental studies was done to appraise the validity of the eight studies in which teaching strategies for undergraduate research have been evaluated. Although the studies sampled had evidence of uncontrolled threats to validity, the research reports emphasized the teaching strategy's "contextual validity" rather than the study's internal or external validity. This insight stimulated questions about the appropriateness of a traditional perspective on validity for research designed to evaluate teaching strategies. Accordingly, a "typology for research on strategies for teaching research," loosely based on Beer and Bloomer's schema for evaluation research, was proposed. The typology consists of four categories of evaluation studies that vary according to purpose, methodological assumptions, types of validity emphasized, and student sample size. The four categories, which are minimally represented in the current literature, are complementary approaches for further evaluation studies of teaching strategies in undergraduate nursing research. PMID- 11214850 TI - The effects of the problem-based Alcohol Early-Intervention Education Package on the knowledge and attitudes of students of nursing. AB - The profession of nursing is seeking to establish its unique professional identity by developing discipline-focused research and clinical practice supported by university education. However, according to refereed literature, educating undergraduate nurses in alcohol-related problems is lacking. The literature reveals that nurses in general lack the necessary knowledge, attitudes, and skills to work with problem drinkers. Alcohol early intervention is advocated as a strategy compatible with contemporary nursing practice. This paper reports a study that commenced with the development of a problem-based, five-week Alcohol Early Intervention Education Package (AEIEP). This package became an intervention around which the knowledge and attitudes of a sample of 212 students of nursing were evaluated. A comprehensive instrument was developed to measure the respondent's knowledge and attitude regarding alcohol-related problems in general and specifically in early intervention. The effects of the education intervention on the different strata of students, were examined in a quasi-experimental, pre-post test design. The findings demonstrated it had a significant effect on the knowledge and attitudes of students enrolled in an integrated bachelor of nursing curriculum. PMID- 11214851 TI - A new module in caring for older adults: problem-based learning and practice portfolios. AB - It is not often that educators have the chance to design a new educational program on the basis of up-to-date and locally relevant research findings. We describe the process by which we designed a new module, aimed at registered nurses who care for older adults in the community. The content of the new module was derived from an analysis of educational needs of the potential student population. The mode of delivery was strongly student-centered, using problem based learning. Assessment was through the building up by students of a practice portfolio. This paper focuses on a description of the new module and how it relates to the findings of the educational needs analysis. The National Board for Nursing, Midwifery and Health Visiting for Scotland put out a tender in 1995 for a community research project on "Educational Provision for Evolving Roles in Community Health Care" (Nursing Times, June, 9, 1995) with the aim of piloting and evaluating an "innovative program which meets changing needs in community health care." A joint bid by Napier University and the University of Glasgow not only proposed to pilot and evaluate the educational program, but also first to develop the content of the program itself through an educational needs analysis. In this paper, we will first provide an outline of the research that underpinned the educational program. Then, we will describe how the results of the needs analysis were implemented into an innovative educational module. Finally, we will give a brief summary of the new module. PMID- 11214852 TI - Assessing the value of the follow-through family project for students and families. AB - Although not a new teaching strategy, the follow-through family assignment is receiving renewed attention from maternity nursing faculty in light of shorter hospital stays and increased competition for clinical sites. The purpose of this evaluation study was to assess the project's value as a learning experience for students and to determine its benefits for participating families. The findings indicate that students enjoyed establishing therapeutic relationships with their families and helping child-bearing families answer health care questions. Students developed primary care skills, increased their self-confidence, and developed an appreciation of childbearing as a transition event for the family. Families appreciated students' educational support and individualized assistance. Families also enjoyed feeling that they had helped their student nurses learn. Overall, the benefits of the follow-through family project appear to outweigh the costs for both students and families. PMID- 11214853 TI - Effects of a modified version of Feeley's Campus Wellness Vacation on baccalaureate registered nurse students' knowledge of and attitudes toward older adults. PMID- 11214854 TI - Using popular culture to teach nursing leadership. PMID- 11214855 TI - Using personal accounts of mental illness as a teaching tool. PMID- 11214856 TI - The role of flow cytometry in the study of cell growth in the rat anterior pituitary gland. AB - Flow cytometry is a suitable technique for studying in vivo and in vitro the cell cycle kinetics of different animal and human tissues, both in normal and tumoral conditions. The rat anterior pituitary gland is a model to investigate cell growth and replication of differentiated, neuroendocrine cells, and we report current evidence on its cell cycle kinetics as well as on the role played by flow cytometry in this type of study. The proliferation potential of normal anterior pituitary cells is related to a number of different conditions, including heterogeneity of cell types, age and sex of donors, and circadian influences. In addition, the trend of cell proliferation in both in vivo and in vitro studies is similar, suggesting that cultured anterior pituitary elements may, at least in part, retain growth features analogous to those of the intact gland. Sorting of selective cell types and analysis of the relation between proliferating anterior pituitary cells and the light-dark cycle have shown that flow cytometry may be useful to investigate the replication process of the gland. By using a combination of flow cytometry, light microscopic immunocytochemistry and morphometry, we have reported a peculiar trend of proliferation in primary monolayer cultures of rat anterior pituitary gland, characterized by a non-linear reduction in their proliferation rate with advancing age, primarily dependent on a reduced transition of cells from the G0/G1- to the early S-phase pool. These studies indicate that flow cytometry offers insights into cell cycle check points of anterior pituitary cells, and suggest that it might be applied to the study of growth of selective pituitary elements, both in normal and tumoral conditions. PMID- 11214857 TI - Characterization of leptin intracellular trafficking. AB - Leptin is produced by adipose tissue, and its concentration in plasma is related to the amount of fat in the body. The leptin receptor (OBR) is a member of the class I cytokine receptor family and several different isoforms, produced by alternative mRNA splicing are found in many tissues, including the hypothalamus. The two predominant isoforms includes a long form (OBR) with an intracellular domain of 303 amino acids and a shorter form (OBR) with an intracellular domain of 34 amino acids. Since OBR, is mainly expressed in the hypotalamus, it has been suggested to be the main signalling form. The peripheral production of leptin by adipocyte tissue and its effects as a signal of satiety in the central nervous system imply that leptin gains access to regions of the brain regulating in energy balance by crossing the blood-brain barrier. In an attempt to characterize the intracellular transport of leptin, we have followed binding internalization and degradation of leptin in HEK293 cells. We have also monitored the intracellular transport pathway of fluorescent conjugated leptin in HEK293 cells. Phenylarsine oxide, a general inhibitor of endocytosis, as well as incubation at mild hypertonic conditions, prevented the uptake of leptin, confirming a receptor mediated internalization process. When internalized, 125I-leptin was rapidly accumulated inside the cells and reached a maximum after 10 min. After 70 minutes about 40-50% of total counts in each time point were found in the medium as TCA soluble material. Leptin sorting, at the level of early endosomes, did not seem to involve recycling endosomes, since FITC-leptin was sorted from Cy3-transferrin containing compartments at 37 degrees C. At 45 minutes of continuos internalization, FITC-leptin appeared mainly accumulated in late endocytic structures colocalizing with internalized rhodamine coupled epidermial growth factor (EGF) and the lysosomal marker protein lamp-1. The transport of leptin was also shown to engage a monensin and bafilomycin sensitive degradation process in lysosomes. Together, our results provide novel data concerning the uptake, intracellular localization and transport of leptin. PMID- 11214858 TI - Different patterns of collagen-proteoglycan interaction: a scanning electron microscopy and atomic force microscopy study. AB - The extracellular matrix of unfixed, unstained rat corneal stroma, visualized with high-resolution scanning electron microscopy and atomic force microscopy after minimal preliminary treatment, appears composed of straight, parallel, uniform collagen fibrils regularly spaced by a three-dimensional, irregular network of thin, delicate proteoglycan filaments. Rat tail tendon, observed under identical conditions, appears instead made of heterogeneous, closely packed fibrils interwoven with orthogonal proteoglycan filaments. Pre-treatment with cupromeronic blue just thickens the filaments without affecting their spatial layout. Digestion with chondroitinase ABC rids the tendon matrix of all its interconnecting filaments while the corneal stroma architecture remains virtually unaffected, its fibrils always being separated by an evident interfibrillar spacing which is never observed in tendon. Our observations indicate that matrix proteoglycans are responsible for both the highly regular interfibrillar spacing which is distinctive of corneal stroma, and the strong interfibrillar binding observed in tendon. These opposite interaction patterns appear to be distinctive of different proteoglycan species. The molecular details of proteoglycan interactions are still incompletely understood and are the subject of ongoing research. PMID- 11214859 TI - The role of the Golgi apparatus during terminal differentiation of mouse urothelial surface cells. AB - The development of the Golgi apparatus in the surface cells of mouse urinary bladder during embryonic development was investigated by electronmicroscopic cytochemistry. The distributions of NADPase and TPPase activities were studied in the urinary bladder during day 15 to day 18 of gestation. At the early embryonic stage, the products of the NADPase and TPPase reactions were visible exclusively in 1 to 2 medial and/or trans Golgi saccules. The strongest increment of NADPase and TPPase positive Golgi cisternae was detected at day 17 when the activity of the urothelial cells was very prominent. At this age, NADPase activity was detected also in lysosomes and on the apical surface of the urothelial cells. The highest distribution pattern of NADPase and TPPase activities observed at this stage rapidly decreases at day 18 of fetal life. The results suggest that the organization of the Golgi apparatus reflected the intensity of the processes occuring in the urothelial cells during gestation. PMID- 11214860 TI - Immunohistochemical observation of actin filaments in epithelial cells encircling the taste pore cavity of rat fungiform papillae. AB - Epithelial cells are connected to each other around taste pores in rat fungiform papillae. Cytoskeletal components are responsible for the maintenance of intracellular adhesion, and we investigated the identification and localization of actin filaments around taste pores. On the basis of observations made by immunohistochemical transmission electron microscopy comparing with confocal laser scanning microscopy using actin-lectin double staining, actin filaments were found to be localized, encircling the squeezed taste pore cavity, in epithelial cells a few micrometers below the papilla surface. In addition, these observations suggest that the organization of actin filaments around taste pores might be involved in the constriction of taste pores. PMID- 11214861 TI - Expression of Tn, sialosyl-Tn and T antigens in human foetal large intestine. AB - Tn, sialosyl-Tn and T antigens are simple mucin-type carbohydrate antigens that may be expressed in human neoplasies due to alteration of the glycoprotein biosynthetic pathway. Utilising specific monoclonal antibodies (HB-Tn1, HB-STn1 and HB-T1), we have investigated the expression of these simple mucin-type carbohydrate antigens in large intestine of 8 human foetuses at early gestational age (9-10 weeks), obtained after therapeutic abortion. In all cases the expression of Tn antigen was mainly localised as a thin rim at the cell membrane and occasionally in the supranuclear region of epithelial cells, while sialosyl Tn antigen was documented in some goblet cell vacuoles and occasionally in the cytoplasm of columnar cells. T antigen was not expressed in any case. These results indicate that Tn and sialosyl-Tn antigens are expressed as early as nine weeks of gestation, further supporting the notion that they may be considered as oncodevelopmental cancer-associated antigens in the large intestine. PMID- 11214862 TI - Cytology of large neurons in the guinea pig dorsal cochlear nucleus contacting the inferior colliculus. AB - Large neurons in the dorsal cochlear nucleus of the guinea pig which project to the inferior colliculus were identified after injections of the neural tracer WGA HRP. Retrograde labelled cells (pyramidal and giant neurons) in the dorsal cochlear nucleus were glycine and GABA immunonegative and showed a similar ultrastructure. Between 30 and 60% of their perimeter was covered by axo-somatic boutons, most of which (>50%) contained pleomorphic synaptic vesicles. Other boutons (about 40% of total) contained flat vesicles and few (5-6%) contained round vesicles, a characteristic of the excitatory cells innervating the inferior colliculus. Immunogold-cytochemistry, coupled to silver intensification, showed that more than 50% of axo-somatic pleomorphic boutons and over 90% of boutons containing flat and pleomorphic vesicles store glycine. Rare WGA-HRP labelled axo somatic boutons containing flat-pleomorphic vesicles were seen on pyramidal and giant neurons. This suggests that a few inhibitory collicular terminals contact the excitatory large neurons in the dorsal cochlear nucleus. PMID- 11214863 TI - Expression of peptidergic and nitrergic structures in dorsal root ganglia of the rabbit. AB - In this study we have demonstrated the presence of neuropeptide substance P (SP)and nonpeptide neurotransmiter NO (nitric oxide) in the dorsal root ganglia (DRG) of rabbits. NADPH-diaphorase histochemical staining was used for detection of NO and an immunohistochemical method for detection of substance P. A number of DRG cells were stained by SP- and NADPH-d reactions. The presence of SP and NADPH diaphorase positive cells varied depending upon the spinal level of the DRG. Positively stained neurons were only small and intermediate in size. Cells of large diameter profiles showed no staining. Substance P immunoreactive cells were of brown and dark brown colour, the intensity of NADPH-d staining varied from light to very dark blue. In some DRG cells, there was very significant neuronal co-localization of immunoreactivity for SP and reactivity for NADPH-d. In summary, DRG cells appear to express diaphorase and substance P activity, and some of them show the presence of both neurotransmitters. Recent studies on the participation of NO in the regulation of SP release in the spinal cord suggest, that also in the DRG neurons there may be a close interaction between NO and SP. PMID- 11214864 TI - Immunohistochemical evidence of seasonal changes of gonadotropes in male ruin lizard (Podarcis sicula campestris De Betta). AB - The pars distalis from the pituitary gland of adult male ruin lizards (Podarcis sicula campestris De Betta), captured during the five periods of the annual sexual cycle (emergence from hibernation, reproductive period, summer regression, autumnal recrudescence, winter arrest), was studied immunohistochemically using specific antibodies against hFSHbeta, hLHbeta, oFSHbeta, and oLHbeta with the avidin-biotin complex (ABC) procedure to monitor the seasonal changes in shape, size and percentage area taken up from gonadotropes. FSH containing cells were specifically identified with anti-hFSHbeta and anti-oFSHbeta sera, whereas the LH cells were localized by anti-hLHbeta. The anti-oLHbeta serum showed cross reactivity with the cells immunostained by the three above antisera (anti hFSHbeta, anti-oFSHbeta, and anti-hLHbeta). None of the cells contained both gonadotropic hormones as shown by the double-immunostaining procedure. Generally, FSH cells were larger and more numerous than LH cells. FSH cells were elongated or pyriform in shape from spring to autumn, whereas they were round or oval during the winter stasis and until the emergence from hibernation. The size and the percentage area occupied by FSH cells showed an annual pattern with two distinct peaks in the reproductive and in the autumnal recrudescence periods. LH cells did not show seasonal changes in shape, being round or oval throughout the reproductive cycle, whereas their size and the area they occupied underwent seasonal variations. The LH cells reached the largest size during the reproductive period and the smallest size during the summer regression. The percentage area occupied by LH cells in the pars distalis peaked at the emergence from hibernation and during the summer refractory period, when FSH cells displayed their lowest values. PMID- 11214865 TI - Immunohistochemical detection of ACTH and MSH cells in the hypophysis of the hermaphroditic teleost, Diplodus sargus. AB - Hypophyseal ACTH and MSH cells were immunohistochemically characterised in the teleost fish, Diplodus sargus, using anti-ACTH (1-24) and anti alpha-MSH polyclonal antisera. ACTH cells were found both in the pars distalis and in the pars intermedia. In the former region, they appeared small, round-shaped and clustered; in the latter, they were either small or large and elongated. Moreover, a few ACTH-immunoreactive cells resembling microglia were present in the neurohypophysis. Conversely, MSH cells were found only in the pars intermedia, and were similar to the larger ACTH cells of the same region. In the pars intermedia, co-localisation of ACTH and MSH immunoreactivity in the same cell was revealed by double immunostaining, though the two hormones were also observed in distinct cell types. The distribution of ACTH cells appeared quite uniform, without any marked difference between the specimens tested. Conversely, MSH cell amount varied according to the stage of the sexual cycle of this teleost fish, which is characterised by protandrous hermaphroditism. In fact, a lower amount of MSH cells were observed in females, whereas no significant difference was found between immature and male specimens. PMID- 11214866 TI - Expression of N-CAM-180 and N-cadherin during development in two South-American anuran species (Bufo arenarum and Hyla nana). AB - Cadherins and N-CAM are Ca++-dependent and Ca++-independent cell adhesion molecules respectively. These molecules play a key role in morphogenesis and histogenesis. We determined the spatiotemporal pattern of N-cadherin and N-CAM 180 kDa expression by immunohistochemistry during development in two South American anuran species (Bufo arenarum, toad and Hyla nana, frog). Both N cadherin and N-CAM were not detectable during early developmental stages. Expression of N-cadherin appeared between the inner and the outer ectoderm layers at stages 19-20. At stages 24-25, N-cadherin was expressed in the neural tube and the heart. In early tadpoles, N-cadherin expression increased along with the central nervous system (CNS) morphogenesis, and reached its maximum level at metamorphic climax stage. N-Cadherin expression was not uniformly distributed. At stage 42, olfactory placodes and retina expressed N-cadherin. Contrary to N-CAM, the strongly myelinated cranial nerves were not labeled. N-Cadherin was present in several mesoderm derivatives such as the notochord, heart and skeletal muscle. The non-neural ectoderm and the endoderm were always negative. Expression of N CAM appeared first in the neural tube at stages 24-25 and the level of expression became uniform from pre-metamorphic to metamorphic climax tadpoles. At this latter stage, a clear N-CAM immunolabeling appeared in the nerve terminals of pharynx and heart. N-Cadherin and N-CAM were found mainly co-expressed in the CNS from early tadpole to metamorphic climax tadpole. Our results show that the expression of N-CAM and N-cadherin is evolutionary conserved. Their increased expression during late developmental stages suggests that N-CAM and N-cadherin are involved in cell contact stabilization during tissue formation. PMID- 11214867 TI - Wavelength dependence of the time course of fluorescence enhancement and photobleaching during irradiation of ethidium bromide-stained nuclei. AB - The variation of fluorescence during irradiation of ethidium bromide-stained nuclei with the 458 nm argon laser line was measured at different wavelengths throughout the emission spectrum. When glycerol was used as a mountant, photoenhancement of fluorescence was observed at all wavelengths, but was greater at the shorter wavelengths. Fluorescence increased by almost one order of magnitude at 500 nm after 40 s of irradiation, compared with only about 10% at wavelengths longer than 600 nm after 2-3 s. In nuclei mounted in phosphate buffer, an initial photoenhancement of fluorescence was detected only at the shorter wavelengths, while continuous photobleaching was observed in the rest of the emission spectrum. When the spectra are normalized to maximum, so as to eliminate the effect of the concurrent photobleaching, it appears that the difference between the time course of fluorescence variation in buffer and glycerol depends largely on the lower photobleaching rate in glycerol. The photoenhancement of fluorescence at shorter wavelengths was found to consist of a band peaking at 485-491 nm in glycerol and at 495-496 nm in buffer. Attenuation of the inner-filter effect contributes minimally to the enhancement of fluorescence at shorter wavelengths. Since the dimer is known to be non fluorescent, the light-induced disaggregation of dimers to monomers cannot be an explanation for the large increase of fluorescence at the shorter wavelengths. The same laser beam that was used to excite the fluorescence of stained nuclei was also used for monitoring the concomitant variation of transmitted light, from which the variation of absorptance during irradiation was computed. While the expected decrease of absorptance was observed in glycerol, reflecting the photodestruction of the fluorophore, in buffer solution an unexpected initial increase was found, which may reflect the accumulation of an absorbing photoproduct. PMID- 11214868 TI - Sorption characteristics of zinc(II) by calcareous soil-radiotracer study. AB - 65Zn was used as a radiotracer to study the sorption characteristics of zinc by two calcareous soils from Gansu Province (China). The sorption and desorption isotherms of Zn on two untreated calcareous soils and on two soils treated to remove CaCO3 were determined at 20 +/- 2 degrees C, pH 7.8 +/- 0.2 in the presence of 0.001 mol/l CaCl2. The contribution of CaCO3 to the Zn sorption by the two calcareous soils was approximately 70% of the total amount sorbed and the sorption-desorption hysteresis was definitely demonstrated, thus the CaCO3 in calcareous soil is undoubtedly the most significant sink for zinc at high pH range. PMID- 11214870 TI - Purification of recovered tellurium dioxide for re-use in iodine radioisotope production. AB - In the production of radioiodine via charged particle activation of isotopically enriched TeO2 and subsequent heating of the irradiated target, some TeO2 is lost. Again, use of recovered TeO2 for radioiodine production showed that impurities are present, which prevent complete volatilization of radioiodine from the heated target. An effective purification procedure for recovered TeO2 has been developed, resulting in a yield of 95-97%. The procedure developed may also be used to purify Te metal. PMID- 11214869 TI - Matrix effects during potassium and calcium determinations in rice saplings using X-ray spectrometery. AB - For selectively excited calcium K X-rays in rice saplings, the relations alpha = N(KR)[1 + A gamma + B beta/(1 + alpha)] and 1/N(Ca) = alpha/beta + b + c beta are found to support the enhancement of potassium K X-rays and N(Ca) calcium K X-ray counts during potassium and calcium determinations, respectively. Here alpha, beta and gamma are weight fractions of potassium, calcium and the matrix substrate, respectively, N(KR) is the relative potassium K X-ray counts of the sample to that of pure potassium and A, B, a, b and c are constants. Tests of these relations, using eight known mixtures of CaCO3, KNO3 and Na2B4O7 10H2O (borax), have further supported the findings. PMID- 11214871 TI - Lyoluminescence characteristics of trehalose dihydrate. AB - Lyoluminescence (LL) of trehalose dihydrate showed a linear gamma ray sensitivity in the dose range 0.1-5 x 10(2) Gy. At increased sample weight dissolved, the LL/mg showed a reduction when the microcontroller based integrated measurement system was used. The LL/mg was found to be independent of the sample weight when the instantaneous peak output observed by the electrometer amplifier on dissolution of the phosphor was taken as a measure of LL yield. The LL spectral measurement of trehalose dihydrate in luminol solution (LL sensitizer) confirms an energy transfer from the radiation induced free radicals to luminol molecule to produce light. PMID- 11214872 TI - Radiological impacts of the amang processing industry on neighbouring residents. AB - The processing of amang (one of a number of tin-tailing products) for its valuable minerals has associated with the radiological and environmental problems. The processing and stockpiling of amang and ilmenite in open-air spaces, subject as it is to environmental influences, gives rise to a potential for affecting residents in adjacent area. A case study was carried out in a residential area neighbouring a typical amang plant to investigate the radiological impact to the residents. The average Effective Dose rates, calculated based on the contributions of Effective Dose rates from inhaled suspended radioactive dust, radon-thoron and their progeny, and external gamma radiation, were determined for selected houses. Results show that the occupants of those houses received Effective Dose rate, which cannot be differentiated from background. The major contributor to the average Effective Dose rate came from external radiation sources. Inhaled radon and its progeny was the second major contributor. PMID- 11214873 TI - Direct radiolabeling of monoclonal antibodies with rhenium-188 for radioimmunotherapy of solid tumors--a review of radiolabeling characteristics, quality control and in vitro stability studies. AB - 188Re is one of the radioisotopes expected to emerge as useful for therapy. Development of new radiopharmaceuticals based on 188Re depends on the radiolabeling methods used, which would give stable complexes having predefined radiochemical properties and in vitro and in vivo stability. This paper has attempted to provide a perspective of 188Re-labeled monoclonal antibodies, their radiolabeling characteristics, methods for quality control of radioimmunoconjugates and in vitro stability for radioimmunotherapy of solid tumors. The direct method of 188Re radiolabeling of antibodies by reductive attachment of 188Re in which free sulfhydryl groups have been generated by reduction of the intramolecular S-S disulfide bonds has been shown to be a promising approach in particular. Moreover, excellent methods have been developed to test the radionuclide, radiochemical purity and stability of 188Re radioimmunoconjugates using high performance liquid chromatography (HPLC) and paper chromatography. PMID- 11214874 TI - Synthesis of a [18F]labeled chelidonine derivative as a possible antitumor agent. AB - [(+/-)-[5bRS-(5b alpha, 6beta, 12b alpha)]-5b,6,7,12b,13,14-hexahydro-13 methyl[1,3]benzodioxolo[5,6-c]-1,3-dioxolo[4,5-1] phenanthridin-6-yl]-4 [18F]fluorobenzoate (6b) an aromatic ester of chelidonine was prepared as a possible PET radiotracer. Compound (6b) was prepared in no-carrier-added (n.c.a) form from the 4-N,N,N-trimethylanilinium triflate derivative (5) in one step. The best results were obtained using Kryptofix(2.2.2)/[18F] and DMSO as the solvent at 90 degrees C. Column chromatography afforded the desired compound in overall radiochemical yield of 65-70% (EOS) with a specific activity of about 3000 Ci/mmole and radiochemical purity greater than 95% in 15 min. PMID- 11214876 TI - Automation of the synthesis of highly concentrated 188Re-MAG3 for intracoronary radiation therapy. AB - We have developed an efficient method and an automated synthetic system for the preparation of highly concentrated 188Re-MAG3. Routine production of 188Re-MAG3 for use in intracoronary radiation therapy was performed by compressed air driven semi-automated shielded system. 188Re-MAG3 was prepared with a commercial kit and reducing agents, purified and concentrated by C18 Sep-Pak cartridges to desired radioactivity and volume. Using this automated system, reproducible radiolabeling yields of 80-85% were obtained. PMID- 11214875 TI - Uptake of the 188Re(V)-DMSA complex by cervical carcinoma cells in nude mice: pharmacokinetics and dosimetry. AB - The uptake of the rhenium-188 (188Re(V)-DMSA) complex of dimercaptosuccinic acid by cervical carcinoma cells in nude mice was evaluated. The pharmacokinetics and dosimetry calculations in normal rats were also evaluated. The images obtained in mice did not show significant accumulation in metabolic organs and the biodistribution studies showed that 3.52 +/- 0.76% of the injected activity per gram (n = 4) was taken up by the tumor. This percentage produces a cumulated activity of 35.63 +/- 8.40 MBq h and an equivalent dose per injected activity of 260 +/- 8.91 mSv/MBq. Pharmacokinetics and dosimetry of the 1887e(V)-DMSA complex indicate that this radiopharmaceutical could be evaluated in patients with soft tissue tumors, since the risk of radiation damage to the kidney or red bone marrow could not be an obstacle for its application in therapeutic nuclear medicine. PMID- 11214877 TI - Synthesis, characterization and biological evaluation of a novel "3 + 1" mixed ligand 99mTc complex having an aliphatic thiol as coligand. AB - A novel "3 + 1" mixed ligand 99mTc complex with N,N-bis(2-mercaptoethyl)-N'N' diethyl-ethilenediamine as ligand and 1-octanethiol as coligand was prepared and evaluated as potential brain radiopharmaceutical. Preparation at tracer level was accomplished by substitution, using 99mTc-glucoheptonate as precursor and a coligand/ligand ratio of 5. Under these conditions the labeling yield was over 80% and a major product with radiochemical purity >80% was isolated by HPLC methods and used for biological evaluation. Chemical characterization at carrier level was developed using the corresponding rhenium and 99gTc complexes. Results were consistent with the expected "3 + 1" structure and X-ray diffraction study demonstrated that the complex adopted a distorted trigonal bipyramidal geometry. All sulphur atoms underwent ionization leading to the formation of a neutral compound. Biodistribution in mice demonstrated early brain uptake, fast blood clearance and excretion through hepatobiliary system. Although brain/blood ratio increased significantly with time, this novel 99mTc complex did not exhibit ideal properties as brain perfusion radiopharmaceutical since brain uptake was too low. PMID- 11214878 TI - Labelling of Re-ABP with 188Re for bone pain palliation. AB - Etidronate and medronate have been labelled with technetium-99m (99mTc-HEDP, 99mTc-MDP) for bone scanning and, with rhenium-188 (188Re-HEDP) to palliate the pain resulting from bone metastases. The objective of this study was to label alendronate, ABP, a new bisphosphonate, with SnF2-reduced-188Re. The reagents for the 5 mg ABP kit were SnF2, KReO4 and gentisic acid at acid pH. The chemical, spectroscopic and microscopic characteristics, quality control, rat bone uptake of [188Re]Re-ABP and similarities with 99mTc-ABP are presented. We conclude that this is a promising new radiopharmaceutical for bone metastases pain palliation. PMID- 11214879 TI - Measurement of the gamma-ray probability per decay of 42K. AB - In the present work, the gamma-ray emission probabilities per decay of 42K transitions have been measured. The activity measurement was carried out in a 4pi (PC)beta-gamma coincidence system. The gamma-ray measurements were performed in a HPGe system. All the uncertainties involved were treated rigorously, by means of covariance analysis. The value of the 1524 keV gamma-ray intensity per decay of 42K obtained in the present work was (0.1813+/-0.0014). This result is compared to the data from other authors. PMID- 11214880 TI - Free parameter, figure of merit and ionization quench in liquid scintillation counting. AB - A statistical study of the detection process demonstrates that the free parameter is essential to compute the counting efficiency in both CIEMAT/NIST and TDCR methods. An analysis of the computed counting efficiencies shows the uselessness of old definition of the figure of merit. A new definition is required and we adopt the idea of taking quantities related with the output of the photomultiplier. In addition, we justify the application of the chemical quenching simulation with the electronic variation of the photomultiplier gain. Finally, we describe a new procedure to determine the figure of merit and the optimum ionization-quenching factor from the pulse spectrum of different radionuclides. The robustness of the new procedure is tested with three different sets of stopping power for low-energy electrons. PMID- 11214881 TI - Total L-shell X-ray production cross sections by 400-700 keV proton impact for elements with 34 < or = Z < or = 53. AB - Total L-shell X-ray production cross sections induced by protons with energies between 400 and 700 keV were measured for elements with atomic number Z between 34 and 53. The ECPSSR theory describes appropriately the results. This model modifies the plane wave born approximation by considering projectile energy loss (E), Coulomb deflection of the incoming ion (C), polarization and change in electron binding energies through a perturbed stationary states method (PSS) and relativistic values of target electron mass (R). A comparison is given with previously published data for proton energies below 1 MeV and 26 < or = Z < or = 53, based on a scaling obtained from a reduced velocity parameter zeta(L)R. The results show that the scaling for these atomic numbers and energy ranges is adequate and a semi-empirical expression to calculate those cross sections is proposed. PMID- 11214882 TI - Dose distributions at extreme irradiation depths of gamma knife radiosurgery: EGS4 Monte Carlo calculations. AB - The accuracy of the dose planning system (Leksell GammaPlan), used in Gamma Knife (type B) radiosurgery at extreme irradiation depths, was verified using the Monte Carlo technique. EGS4 Monte Carlo calculations were employed to calculate the dose distribution along the x, y and z axes for an irradiation relatively shallow in a spherical bony cavity water phantom. Two different sizes of the collimator helmets, 8 and 18 mm, of the Leksell Gamma Knife Unit were studied. The results of GammaPlan showed good consistency with the Monte Carlo results. Furthermore, small dose enhancements were observed in the skull bone where accurate dose measurements are difficult due to the presence of the air-phantom interface. Therefore, the results of this project can promote confidence to all Gamma Knife centres in the world when using the Leksell GammaPlan. PMID- 11214883 TI - Determination of 222Rn emanation fraction and diffusion coefficient in concrete using accumulation chambers and the influence of humidity and radium distribution. AB - In this paper we present a laboratory method for the determination of diffusion coefficient, D, as well as the 222Rn emanation fraction, f, in concrete core samples. It is based either on the analyses of the growth curves of the radon in the air volume surrounding a sample enclosed in an accumulation chamber (Lucas cell or RADIM device) or using the charcoal adsorption method. Samples used have a special geometry allowing the assumption of a one-dimensional diffusion of radon in material. Radium was enhanced in the concrete samples by adding radium bromide solution or uranium ore. A strong dependence of the emanation fraction on the enhancing method was observed. For the sample enhanced with uranium ore the specific exhalation rate was about ten times smaller. A marked dependence of radon exhalation on the water content was also observed. PMID- 11214884 TI - Application of concentrated TiO2 sols for gamma-ray radiation dosimetry. AB - Upon exposure to gamma-radiation, a concentrated TiO2 sol changes from colorless to deep blue with an absorption maximum at 540 nm. The absorption has been assigned to trapped electrons or Ti3+ states in the solid matrix based on its spectroscopic similarity to the samples irradiated with UV light. Unlike the conduction-band electrons generated from direct excitation by UV radiation, the origin of the trapped electrons during gamma-ray irradiation may be traced to a series of reducing species produced by the high energy electrons, which in turn, are the direct result of gamma-irradiation. As the absorption intensity is linearly related to the duration of exposure to gamma-radiation, it may have an application in gamma-ray dosimetry. The sensitivity of its dosage response has been found to be influenced by the semiconductor particle concentration and the dispersing solvent. PMID- 11214885 TI - Absolute measurements of photon emission probabilities of 169Yb. AB - A solution of 169Yb was absolutely standardized by the 4pi(EC,X)-gamma coincidence counting method and the result was used to obtain direct measurements of gamma-ray emission probabilities with a coaxial HPGe detector. The empirical relation proposed by (Vano, F., Gonzalez, L., Gaeta R., Gonzalez, J.A., 1975. An empirical function which relates the slope of the Ge efficiency curves and the active volume Nucl. Instr. Meth. 123, 573) was tested using the gamma spectral response above 200 keV. The half-life of 169Yb was also measured with a 4pi gamma ionization chamber. PMID- 11214887 TI - Evaluation of airborne gamma-ray spectrometric data for the Missikat uranium deposit, Eastern Desert, Egypt. AB - The examination of gamma-ray spectrometric data of the Missikat area was found to be useful in locating areas worth exploring for uranium occurrence. The statistical treatment of these data shows that the uranium threshold level is 13 ppm. Such a value represents indirectly the presence of uranium mineralization and identifies anomalous areas on the eU contour map in the northern border of the Missikat-Ria El Gerra granitic plutons. This area should be of prime concern in uranium exploration of these plutons. The interpretation of the variation in the eU/eTh ratio with eU and eTh suggests that uranium redistribution has occurred within the Missikat-Ria El Gerra granitic plutons. Uranium may be reconcentrated in silicification, sericitization and kaolinization alterations which are geologically evident. eU, eTh and their ratio eU/eTh for the Missikat Ria El Gerra granites exhibit a lognormal distribution which is in agreement with the general distribution of trace elements, whereas the K content tends towards a normal distribution. PMID- 11214886 TI - Intercomparison of 131I and 99mTc activity measurements in Brazilian nuclear medicine services. AB - This work outlines the quality assurance program for the activity measurements of the most used radionuclides at Brazilian Nuclear Medicine Services (NMS). The program aims to guarantee that the patient is given the correct prescribed amount of activity in diagnostic or therapeutic applications. This accurate administration depends upon proper use and calibration of the activity meters by the NMS. Underestimation of administered activity in diagnostic practices could delay correct diagnosis disturbing the value of the investigation. On the other hand, the overestimation would be worse, mainly in therapeutic applications, because an unnecessarily high absorbed dose would be delivered to the patient. The preliminary results of intercomparison for 131I and 99mTc showed that many activity meters used at NMS's present problems giving results up to 41% greater than the reference values determined at the National Metrology Laboratory for Ionizing Radiation (LNMRI) which is recognized as the Brazilian authorized metrology laboratory for ionizing radiation. These results have demonstrated that the NMS should improve the accuracy of the activity measurements of the radionuclides administered to the patients and establish the traceability to the national standards of measurements. These standards are based on a pressurized well-type ionization chamber installed at LNMRI and calibrated with reference sources standardized by absolute methods. The protocol of the intercomparison and recommendations made in order to minimize errors in measuring procedures are described and results are discussed. PMID- 11214888 TI - The effect of heterogeneity in gamma-ray albedo analysis of mineral raw materials. AB - The influence of heterogeneity on the results of a gamma-ray albedo analysis of heterogeneous raw materials has been considered. The heterogeneity error components, caused by dispersing the defined element in the bulk under study and by the direct influence of the particles dimension (grain size) on the intensity of the scattered gamma-rays, have been determined. Mathematical models to describe the dependence of the error on the chemical composition of the raw material under study, the component densities, the particles dimensions and the primary gamma-radiation energy have been suggested. PMID- 11214889 TI - Application of PGNAA for bulk coal samples in a 4pi geometry. AB - A 4pi geometry bulk coal analyser using the Prompt gamma neutron activation analysis (PGNAA) technique was tested in the laboratory. The volume of the bulk samples was 270 litres. A 1.5 microg 252Cf neutron source and a 75 mm x 35 mm dia BGO detector were used for the measurements. The ash, Fe, Si and Al content of coal were determined with good accuracy. PMID- 11214890 TI - The subsoil gamma-ray intensity distribution in the Oriental Region of the Republic of Paraguay. AB - Subsoil gamma-ray intensity measurements are used in uranium prospecting and in the classification of lithologies. This work charts the subsoil gamma-ray intensity distribution in the Oriental Region of the Republic of Paraguay, a centrally located country in South America. Gamma-ray count rates were obtained at depths of 5, 10, 50, and 100 m in 158 wells and count rate contour maps were generated for each of the depths. Three regions of gamma-ray anomalies were identified. PMID- 11214891 TI - Cluster analysis of radionuclide concentrations in beach sand. AB - This paper presents a method in which natural radionuclide concentrations of beach sand minerals are traced along a stretch of coast by cluster analysis. This analysis yields two groups of mineral deposit with different origins. The method deviates from standard methods of following dispersal of radionuclides in the environment, which are usually based on the construction of lines of equal concentrations. The paper focuses on the methodology of quantitatively correlating activity concentrations of natural radionuclides in two groups of minerals. The methodology is widely applicable, but is demonstrated for natural radioactivity in beach sands along the coast of South West Australia. PMID- 11214892 TI - Geophysical natural gamma-ray well logging and spectrometric signatures of south AL-Abter phosphatic deposits in Syria. AB - A combination of several exploration techniques was carried out in AL-Abter region, aiming at outlining the main characteristics of the phosphatic layers in this region. The techniques used in this research are natural 7-ray well logging, gamma and alpha-spectrometry. It is shown that uranium concentrations in the samples taken from the wells studied vary between 42.8 and 112.5 ppm with a standard deviation of 15.2 ppm. The P2O5 content varies between 20.5% and 28.31% with a standard deviation of 3.11% and the radioactive intensities vary between 150 and 275 counts per second (cps) with a standard deviation of 31 cps. The ratio of 234U/238U in the analyzed samples indicates that the study region is in radioactive equilibrium. The affinity of uranium and P2O5 to some trace elements, such as V, Sr, Cu and Ni has been verified through studying the correlation matrix of these elements. PMID- 11214893 TI - Elemental analysis of two Egyptian iron ores and produced industrial iron samples by neutron activation analysis. AB - Elemental analysis of two iron ores and initial industrial iron production prepared by the Egyptian Iron and Steel Company of Helwan near Cairo were performed by the instrumental neutron activation analysis technique. Five samples of each type were irradiated for 48 h in a thermal neutron flux of 4 x 10(12) n/cm2 s in the first Egyptian research reactor ET-RR-1. Also, the Pneumatic Irradiation Rabbit System (PIRS), attached to the reactor ET-RR-1 in Inshass, was used to measure short-life elements. The gamma-ray spectra were obtained with a hyper pure germanium detection system. The concentration percentage values of major, minor and trace elements are presented. Implications of the elemental concentration values obtained are presented. PMID- 11214894 TI - Determining soil contamination profiles from intensities of capture-gamma rays using above-surface neutron sources. AB - Four methods are presented to estimate contaminant concentration profiles in soil from the intensities of neutron-induced capture-gamma photon intensities measured at the soil surface. In particular, the method of linear regularization with and without an iterative positivity constraint, the Backus-Gilbert method, and the maximum entropy method are applied to the soil contamination problem. Example results obtained with the four methods are given for photon intensities calculated for idealized test contaminant profiles in soil irradiated by neutron sources above the surface. PMID- 11214895 TI - Cognitive performance and muscle activation in workers with chronic shoulder myalgia. AB - The present study determined whether workers with chronic shoulder myalgia exhibit impaired cognitive performance and elevated muscle activation. Ten workers with and 10 without shoulder myalgia performed three sessions, each consisting of three different cognitive tasks. Subjective pain was reported on visual analogue scales (VAS). Surface electromyography was recorded bilaterally from the trapezius and forearm extensor muscles. Speed and error rates of the cognitive work were almost the same in the two groups, but the myalgia subjects reported more stress during the work. In two of the cognitive tasks, both groups increased their speed of performance to the same extent from the first to the third session, despite pain increase in the myalgia subjects. In the biomechanically demanding task, the speed fell from the first to the third session in both groups. Muscle activation was equal in the two groups and constant throughout the protocol despite changes in speed of performance and pain. It is concluded that localized chronic muscle pain does not significantly alter cognitive performance, or muscle activation level during cognitive work. However, the perceived burden of work is larger, as indicated by the higher stress reported during cognitive work in the myalgia subjects compared with their pain-free controls. PMID- 11214896 TI - Pattern recognition for road traffic accident severity in Korea. AB - An increasing number of road traffic accidents (RTA) in Korea has emerged as being harmful both for the economy and for safety. An accurately estimated classification model for several severity types of RTA as a function of related factors provides crucial information for the prevention of potential accidents. Here, three data-mining techniques (neural network, logistic regression, decision tree) are used to select a set of influential factors and to build up classification models for accident severity. The three approaches are then compared in terms of classification accuracy. The finding is that accuracy does not differ significantly for each model and that the protective device is the most important factor in the accident severity variation. PMID- 11214897 TI - Theories of musculoskeletal injury causation. AB - Based on the scientific evidence in published literature about precipitation of musculoskeletal injuries in the workplace, four theories have been proposed to explain these afflictions. Central to all theories is the presupposition that all occupational musculoskeletal injuries are biomechanical in nature. Disruption of mechanical order of a biological system is dependent on the individual components and their mechanical properties. These common denominators will be causally affected by the individual's genetic endowment, morphological characteristics and psychosocial makeup, and by the occupational biomechanical hazards. This phenomenon is explained by the Multivariate Interaction Theory. Differential Fatigue Theory accounts for unbalanced and asymmetric occupational activities creating differential fatigue and thereby a kinetic and kinematic imbalance resulting in injury precipitation. Cumulative Load Theory suggests a threshold range of load and repetition product beyond which injury precipitates, as all material substances have a finite life. Finally, Overexertion Theory claims that exertion exceeding the tolerance limit precipitates occupational musculoskeletal injury. It is also suggested that while these theories may explain the immediate mechanism of precipitation of injuries, they all operate simultaneously and interact to modulate injuries to varying degrees in different cases. PMID- 11214898 TI - Can accelerometry accurately predict the energy cost of uphill/downhill walking? AB - To evaluate whether an activity monitor based on body acceleration measurement can accurately assess the energy cost of the human locomotion, 12 subjects walked a combination of three different speeds (preferred speed +/- 1 km/h) and seven slopes (-15 to +15% by steps of 5%) on a treadmill. Body accelerations were recorded using a triaxial accelerometer attached to the low back. The mean of the integral of the vector magnitude (norm) of the accelerations (mIAN) was calculated. VO2 was measured using continuous indirect calorimetry. When the results were separately analysed for each incline, mIAN was correlated to VO2 (average r = 0.87, p<0.001, n = 36). VO2 was not significantly correlated to mIAN when data were globally analysed (n = 252). Large relative errors occurred when predicted VO2 (estimated from data of level walking) was compared with measured VO2 for different inclines (-53% at +15% incline, to +55% at -15% incline). It is concluded that without an external measurement of the slope, the standard method of analysis of body accelerations cannot accurately predict the energy cost of uphill or downhill walking. PMID- 11214899 TI - Change in pattern of absenteeism as a result of workplace intervention for personnel support. AB - The aim was to investigate whether a preventive intervention carried out in a predominantly female workplace, that of hospital cleaners (consisting of a group of 97 women), had any effect on patterns of absenteeism. As a background, a model for analysing complex patterns of absenteeism, including sickness absences, was also developed. A further aim was to study the interactions between different forms of absenteeism. Comparison was made with a reference group consisting of employees in the same job category who only received the customary personnel support. For individuals in the intervention group who were < 42 years of age, total absence due to sickness decreased. In a multiple regression analysis, the contribution from the intervention to the decrease was significant at the 5% level. This change was particularly obvious in those who had a previous history of high absence due to sickness. No clear relationship was shown between short term absenteeism and the interventions applied. For those who were > 42 years, short-term absence decreased for those who had been in the same jobs for a long time. The combination of increased age and experience showed a tendency to enhance this decline in short-term absenteeism due to sickness. For those > 42 years, and who at the same time have a previous history of high absenteeism, long term absenteeism due to sickness seemed to be increasing. Increased experience tended to reduce this increase in long-term sickness absence. This combination of different effects possibly indicated the presence of a process of selection which determined who remained in the job as opposed to those who did not. An important conclusion is that different forms of absenteeism need to be looked at in parallel, and at the same time multivariate statistical analysis needs to be carried out to determine the different interactions between the factors. PMID- 11214900 TI - Vigilance on the civil flight deck: incidence of sleepiness and sleep during long haul flights and associated changes in physiological parameters. AB - The study investigated sleepiness and sleep in aircrew during long-haul flights. The objectives were to identify loss of alertness and to recommend a practical approach to the design of an alerting system to be used by aircrew to prevent involuntary sleep. The flights were between London and Miami, covering both day- and night-time sectors, each with a duration of approximately 9 h. The subjects were 12 British Airways pilots. Various physiological variables were measured that could potentially be used to indicate the presence of drowsiness and involuntary sleep: brain electrical activity (electroencephalogram, EEG), eye movements via the electro-oculogram (EOG), wrist activity, head movements and galvanic skin resistance. The EEG and EOG identified sleepiness and sleep, as well as being potential measures on which to base an alarm system. Ten pilots either slept or showed evidence of sleepiness as assessed by the EEG and EOG. Many of the episodes of sleepiness lasted < 20 s, which could mean that the subjects were unaware of their occurrence and of the potential consequences on performance and vigilance. All physiological parameters showed changes during sleep, although only the EEG and EOG were modified by sleepiness. During sleep, skin resistance was increased, and wrist activity and head movements were absent for long periods. The study indicated that the measurement of eye movements (either alone or in combination with the EEG), wrist activity or head movement may be used as the basis of an alarm system to prevent involuntary sleep. Skin resistance is considered to be unsuitable, however, being related in a more general way to fatigue rather than to sleep episodes. The optimal way to monitor the onset of sleep would be to measure eye movements; however, this is not feasible in the flight deck environment at the present time due to the intrusive nature of the recording methodology. Wrist activity is therefore recommended as the basis of an alertness alarm. Such a device would alert the pilot after approximately 4-5 min of wrist inactivity, since this duration has been shown by the present study to be associated with sleep. The possibility that sleep inertia (reduced alertness immediately after awakening from sleep) could follow periods of sleep lasting 5 min needs to be considered. The findings reported here might be applicable to other occupational environments where fatigue and sleepiness are known to occur. PMID- 11214901 TI - The human olfactory subgenome: from sequence to structure and evolution. AB - Olfactory receptors (ORs) constitute the largest multigene family in multicellular organisms. Their evolutionary proliferation has been driven by the need to provide recognition capacity for millions of potential odorants with arbitrary chemical configurations. Human genome sequencing has provided a highly informative picture of the "olfactory subgenome", the repertoire of OR genes. We describe here an analysis of 224 human OR genes, a much larger number than hitherto systematically analyzed. These are derived by literature survey, data mining at 14 genomic clusters, and by an OR-targeted experimental sequencing strategy. The presented set contains at least 53% pseudogenes and is minimally divided into 11 gene families. One of these (no. 7) has undergone a particularly extensive expansion in primates. The analysis of this collection leads to insight into the origin of OR genes, suggesting a graded expansion through mammalian evolution. It also allows us to delineate a structural map of the respective proteins. A sequence database and analysis package is provided (http://bioinformatics.weizmann.ac.il/HORDE), which will be useful for analyzing human OR sequences genome-wide. PMID- 11214902 TI - A silent mutation induces exon skipping in the phenylalanine hydroxylase gene in phenylketonuria. AB - An A-->T substitution in cDNA nucleotide 1197 (c.1197A/T) of the human phenylalanine hydroxylase (PAH) gene has been regarded as a silent mutation, because both the wild-type (GUA) and the mutant (GUU) alleles encode a valine residue at codon 399 (V399 V). The nucleotide c.1197 is located at the 3'-end of exon 11at position -3 of the exon-intron junction. To explore whether the substitution exerts any effects on the processing of the PAH mRNA, illegitimate PAH transcripts from lymphoblast cultures of a phenylketonuria (PKU) patient heterozygous for c.1197A/T were analyzed by the polymerase chain reaction following reverse-transcription (RT-PCR). mRNAs with an exon 11 deletion were revealed. Furthermore, by using an R408 W mutation in the paternal allele as a marker, sequence analysis of the RT-PCR products indicates that virtually all PAH transcripts from the maternal allele with the c. 1197A/T substitution do not contain exon 11. To address whether this substitution is the main determinant for exon skipping, PAH minigenes with or without the substitution were constructed and transfected to a human hepatoma cell line. Analysis of the transcription products by S1 nuclease mapping clearly indicated that such exon 11 skipping was directly associated with the c.1197A/T substitution. Thus, this study demonstrates that the c.1197A/T substitution in the PAH gene is not just a neutral polymorphism but a mutation that induces post-transcriptional skipping of exon 11 leading to a PKU phenotype. PMID- 11214903 TI - Patterns of haplotype diversity within the serpin gene cluster at 14q32.1: insights into the natural history of the alpha1-antitrypsin polymorphism. AB - The levels of haplotype diversity associated with different alpha1-antitrypsin (PI) alleles were assessed by the analysis of three microsatellites located within or close to corticosteroid-binding globulin (CBG), alpha1-antitrypsin [PI (TG)n] and protein C inhibitor [PCI-(TG)n] loci in three populations with different historic backgrounds: Portugal, the Basque Country and Sao Tome Principe (Gulf of Guinea). Unlike the more distant PCI-(TG)n repeat, allelic variation at PI-(TG)n reflected distinct phases of mutational recovery of microsatellite diversity around different founder alleles and showed a considerable differentiation between alpha1-antitrypsin protein variants. In accordance with population history, the Basque sample presented overall reduced levels of microsatellite variation. The African sample, although presenting the highest PCI-(TG)n diversity, showed a lineage-specific reduction in PI-(TG)n heterozygosity within the oldest M1Ala213 variant that could have been caused by (1) selection at a closely linked locus or (2) biases in the microsatellite mutation process leading to a stable equilibrium distribution. Age estimates of alpha1-antitrypsin variants based on microsatellite variation suggest that the Z deficiency allele appeared 107-135 generations ago and could have been spread in Neolithic times. The S mutation has an older 279- to 470-generation age, indicating that its high frequencies in Iberia did not result from a recent bottleneck and that PI*S could have originated in this region. M2 and M3 types had lower age estimates than would be expected from their wide geographical distributions, suggesting that their dispersion in Europe might have been preceded by important bottlenecks. PMID- 11214904 TI - Transmission ratio distortion in offspring of heterozygous female carriers of Robertsonian translocations. AB - Robertsonian translocations are the most common structural rearrangements of human chromosomes. Although segregation of Robertsonian chromosomes has been examined in many families, there is little consensus on whether inheritance in the balanced progeny conforms to Mendelian ratios. To address this question, we have compiled previously reported segregation data, by sex of parent, for 677 balanced offspring of Robertsonian carriers from 82 informative families and from a prenatal diagnosis study on the risk of unbalanced offspring in carriers of chromosome rearrangements. Care was taken to avoid any source of ascertainment bias. Our analysis supports the following conclusions: (1) the transmission ratio is not independent of the sex of the carrier; (2) the transmission ratio distortion is observed consistently only among the offspring of carrier females; (3) the transmission ratio distortion does not appear to be dependent on the presence of a specific acrocentric chromosome in the rearrangement. The sex-of parent-specific origin of the non-Mendelian inheritance, the finding that the rearranged ("mutant") chromosomes are recovered at significantly higher frequency than the acrocentric ("normal") chromosomes, and the similarities between these observations and the segregation of analogous rearrangements through female meiosis in other vertebrates strongly support the hypothesis that the transmission ratio distortion in favor of Robertsonian translocations in the human results from the preferential segregation of chromosomes during the first meiotic division. This non-Mendelian inheritance will result in increased overall risk of aneuploidies in the families of Robertsonian translocation carriers, independently of the origin of the transmission ratio distortion. PMID- 11214905 TI - Human type I hair keratin pseudogene phihHaA has functional orthologs in the chimpanzee and gorilla: evidence for recent inactivation of the human gene after the Pan-Homo divergence. AB - In addition to nine functional genes, the human type I hair keratin gene cluster contains a pseudogene, phihHaA (KRTHAP1), which is thought to have been inactivated by a single base-pair substitution that introduced a premature TGA termination codon into exon 4. Large-scale genotyping of human, chimpanzee, and gorilla DNAs revealed the homozygous presence of the phihHaA nonsense mutation in humans of different ethnic backgrounds, but its absence in the functional orthologous chimpanzee (cHaA) and gorilla (gHaA) genes. Expression analyses of the encoded cHaA and gHaA hair keratins served to highlight dramatic differences between the hair keratin phenotypes of contemporary humans and the great apes. The relative numbers of synonymous and non-synonymous substitutions in the phihHaA and cHaA genes, as inferred by using the gHaA gene as an outgroup, suggest that the human hHaA gene was inactivated only recently, viz., less than 240,000 years ago. This implies that the hair keratin phenotype of hominids prior to this date, and after the Pan-Homo divergence some 5.5 million years ago, could have been identical to that of the great apes. In addition, the homozygous presence of the phihHaA exon 4 nonsense mutation in some of the earliest branching lineages among extant human populations lends strong support to the "single African origin" hypothesis of modern humans. PMID- 11214906 TI - A detailed analysis of the MECP2 gene: prevalence of recurrent mutations and gross DNA rearrangements in Rett syndrome patients. AB - Mutations in the X-linked methyl-CpG-binding protein 2 gene (MECP2) have been found to be a cause of Rett syndrome (RTT). In order to provide further insights into the distribution and the spectrum of mutations, we investigated, in addition to the whole coding sequence, a phylogenetically conserved sequence within the 3' untranslated region (3' UTR) of the MECP2 gene for 55 sporadic RTT, including 47 typical and 8 nonclassical cases. We have developed an approach based on conformation-sensitive gel electrophoresis, sequence analysis and, for the first time, Southern blot analysis. Mutation detection, including unreported gross DNA rearrangements, was achieved in 79% of classical RTT and 25% of nonclassical RTT patients. The high prevalence of recurrent mutations allows us to propose a molecular diagnosis strategy for RTT. PMID- 11214907 TI - Diverse prevalence of large deletions within the OA1 gene in ocular albinism type 1 patients from Europe and North America. AB - Ocular albinism type 1 (OA1) is an X-linked disorder mainly characterized by congenital nystagmus and photodysphoria, moderate to severe reduction of visual acuity, hypopigmentation of the retina, and the presence of macromelanosomes in the skin and eyes. We have previously isolated the gene for OA1 and characterized its protein product as melanosomal membrane glycoprotein displaying structural and functional features of G protein-coupled receptors. We and others have identified mutations of various types within the OA1 gene in patients with this disorder, including deletions and splice site, frameshift, nonsense, and missense mutations. However, different prevalences of large intragenic deletions have been reported, ranging from 10% to 50% in independent studies. To determine whether these differences might be related to the geographic origin of the OA1 families tested, we performed a further extensive mutation analysis study leading to the identification of pathogenic mutations in 30 unrelated OA1 patients mainly from Europe and North America. These results, together with our earlier mutation reports on OA1, allow us to resolve the apparent discrepancies between previous studies and point to a substantial difference in the frequency of large intragenic deletions in European (<10%) compared with North American (>50%) OA1 families. These observations and our overall refinement of point mutation distribution within the OA1 gene have important implications for the molecular diagnosis of OA1 and for the establishment of any mutation detection program for this disorder. PMID- 11214908 TI - The relationship between Y chromosome DNA haplotypes and Y chromosome deletions leading to male infertility. AB - Microdeletions on the short arm of the Y chromosome have defined three non overlapping regions (AZFa, b, c) recurrently deleted among infertile males. These regions contain several genes or gene families involved in male germ-cell development and maintenance. Even though a meiotic origin for these microdeletions is assumed, the mechanisms and causes leading to microdeletion formation are largely unknown. In order to assess whether some Y chromosome groups (or haplogroups) are predisposed to, or protected against, deletion formation during male meiosis, we have defined and compared Y chromosome haplogroup distribution in a group of infertile/subfertile males harbouring Yq deletions and in a relevant Northwestern European control population. Our analyses suggest that Y chromosome deletion formation is, at least in the study populations, a stochastic event independent of the Y chromosome background on which they arise and may be caused by other genetic and/or environmental factors. PMID- 11214909 TI - AFLP fingerprinting of the human genome. AB - Elucidation of the genetic basis of complex traits and diseases in humans includes the use of genome-wide association studies that depend on the analysis of a large number of diallelic markers. We describe the application of the amplified fragment length polymorphism (AFLP) technique as an efficient approach for rapidly identifying and scoring multiple variants in the human genome. Using a commercially available kit, we found that AFLP yields reproducible DNA fingerprints consisting of 42-132 fragments, 8% of which show variability between individuals. These variant markers appear to be from different chromosomes, and the majority of them is diallelic. Based on the information obtained in this study, it is possible to approximate the minimum number of selective AFLP primer combinations needed to approach a desired coverage density of all chromosomes. To our knowledge, this is the first study showing the general applicability of AFLP in humans and providing a constructive guide for the design of genomic studies in Homo sapiens with this robust methodology. PMID- 11214910 TI - Novel missense mutations outside the allosteric domain of glutamate dehydrogenase are prevalent in European patients with the congenital hyperinsulinism hyperammonemia syndrome. AB - The hyperinsulinism-hyperammonemia syndrome (HHS) has been shown to result from 'gain-of-function' mutations of the glutamate dehydrogenase (GlDH) gene, GLUD1. In the original report, all mutations were found in a narrow range of 27 base pairs within exons 11 and 12 which predicted an effect on the presumed allosteric domain of the enzyme and all these mutations were associated by a diminished inhibitory effect of guanosine triphosphate (GTP) on GlDH activity. We have investigated 14 patients from seven European families with mild hyperinsulinism. In four families, more than one member was affected. In eight cases hyperammonemia was documented, and eight cases had signs of significant leucine sensitivity. In one of the families, a novel heterozygous missense mutation in exon 6 [c.833C>T (R221C)] was detected, and in all other cases from six unrelated families the novel heterozygous missense mutation c.978G>A (R269H) was found in exon 7. When GIDH activity was measured in lymphocytes isolated from affected patients, both mutations were shown to result in a normal basal activity but a diminished sensitivity to GTP. It is the first time that this effect is reported for mutations located in the presumed catalytic site and outside the GTP allosteric domain of the enzyme. The observation of the high prevalence of the exon 7 mutation both in familial and sporadic cases of HHS suggests a mutation hot spot and justifies a mutation screening for this novel mutation by mismatch PCR-based restriction enzyme digestion in patients with hyperinsulinism. PMID- 11214911 TI - The Frequency of Inherited Disorders Database. PMID- 11214912 TI - A transgenic model of a familial prion disease. AB - We have generated lines of transgenic mice that express a mutant prion protein containing 14 octapeptide repeats whose human homologue is associated with an inherited prion dementia. These mice develop an ataxic illness that begins at 65 days of age when the transgene array is homozygous, and results in death by 115 138 days. Starting from birth, mutant PrP is converted into a protease-resistant and detergent-insoluble form that resembles PrP(Sc), and this form accumulates dramatically in many brain regions throughout the lifetime of the mice. As PrP accumulates, there is massive apoptosis of cerebellar granule cells, as well as astrocytosis and deposition of PrP in a punctate pattern. These results establish a new transgenic animal model of an inherited human prion disease, and provide important insights into the molecular pathogenesis of these disorders. PMID- 11214913 TI - Transgenic models of prion disease. AB - There is growing concern that bovine spongiform encephalopathy (BSE) may have passed from cattle to humans, resulting in approximately 70 cases of an atypical, variant CJD (vCJD) in teenagers and young adults. We report here that transgenic (Tg) mice expressing full-length bovine (Bo) PrP serially propagate BSE prions and that there is no species barrier for transmission from cattle to Tg(BoPrP) mice. Surprisingly, these same mice were also highly susceptible to vCJD and natural sheep scrapie. The incubation times (approximately 250 d), neuropathology, and PrP(Sc) isoforms in Tg(BoPrP) mice inoculated with vCJD and BSE brain extracts were indistinguishable and differed dramatically from those seen in these mice injected with natural scrapie. In efforts to identify PrP sequences required for prion formation, we found that a redacted prion protein of only 106 amino acids (PrP106) containing two large deletions supported prion propagation. In Tg(PrP106) mice, an artificial transmission barrier for the passage of full-length mouse prions was diminished by the coexpression of full length wt MoPrP(C), suggesting that wt MoPrP acts in trans to accelerate the replication of "miniprions" containing PrP(Sc)106. Following a single passage (approximately 300 d) in Tg(PrP106) mice, the miniprions efficiently transmitted disease to Tg(PrP106) mice after only approximately 66 days. Our findings with Tg(BoPrP) mice provide compelling evidence that prions from cattle with BSE have infected humans and caused fatal neurodegeneration, the unique features of miniprions offer new insights into the mechanism of prion replication, and the trans-acting effects of full-length PrP coexpression suggest a new approach to the development of even more efficient animal models for prion diseases. PMID- 11214914 TI - Surveillance of BSE. AB - The current method used to identify suspect BSE cases is based on reporting cattle displaying clinical signs compatible with BSE. The reporting of such cases is dependent on the ability of farmers and veterinarians to recognise the disease symptoms and on the willingness to report such cases. Furthermore, it depends on the stage of the disease, because early clinical signs of BSE are not always typical. Histology and immunohistochemistry are established and reliable to confirm BSE in cattle, but the procedure is cumbersome, time consuming and therefore not suited for mass testing of animals. A targeted surveillance system using the Prionics-Western-Blot Test was initiated in Switzerland in 1999. Prionics-positive results are confirmed by histology or immunohistochemistry by the BSE-reference laboratory. This surveillance scheme has confirmed fallen stock and cows subjected to emergency slaughter as the major risk groups. Currently all cattle from these two categories are tested. As a further measure a random sample of cows from regular slaughtering is tested. This enables to determine the BSE status independent of the inaccuracies of a clinical case reporting system. This approach may be helpful to reliably assess the BSE situation in countries with low incidence in order to verify their BSE status and in countries which want to prove their BSE-free status. PMID- 11214915 TI - Follicular dendritic cells in scrapie pathogenesis. AB - Scrapie pathogenesis was studied in chimaeric mice that carried the prion protein (PrP) gene only in particular cells of the immune system. These mice were produced by grafting bone marrow from PrP expressing donors into PrP deficient recipients and vice versa. As follicular dendritic cells are not replaced significantly from the bone marrow in adult mice, this procedure resulted in a mismatch in PrP genotype between these cells and bone marrow derived cells such as lymphocytes. Using these models we obtained strong evidence that follicular dendritic cells produced high levels of the normal form of PrP in uninfected mice. Furthermore, the replication of a mouse-passaged scrapie strain in the spleen depended only on the presence of PrP expressing follicular dendritic cells. PrP expression by lymphocytes or other bone marrow derived cells had no influence on replication in spleen or on neuroinvasion in these models. These results indicate that the follicular dendritic cell is a potential target for prophylactic or therapeutic intervention in transmissible spongiform encephalopathies. PMID- 11214916 TI - Histopathology and immunohistochemistry of human transmissible spongiform encephalopathies (TSEs). AB - Neuropathological examination has remained the most important tool to give a definite diagnosis of human transmissible spongiform encephalopathies (TSEs). In recent years, immunohistochemistry (IHC) for the disease-associated prion protein (PrP) has emerged as an indispensable adjunct to the neuropathological confirmation of TSEs, especially in cases with equivocal histopathological changes. The clinico-pathological phenotype including histopathology and IHC for PrP depends upon PrPres fragment size and codon 129 genotype in the PrP gene, PRNP. However, some TSEs have little or no spongiform change or detectable PrP, such as fatal familial insomnia (FFI). IHC for PrP requires appropriate technique, has some pitfalls and thus should be interpreted by experienced observers. The amount and distribution of PrP deposits do not always correlate with type and severity of local tissue damage. PrP deposition occurs only where neuronal parenchyma is present; in pre-existing tissue lesions such as scarred infarctions with prominent gliosis, PrP does not accumulate. Most recently, new patterns of granular ganglionic and tiny adaxonal PrP deposits were described in the peripheral nervous system in rare human TSE cases and experimental scrapie. There is early, severe and selective loss of a peculiar parvalbumin-expressing subset of inhibitory GABAergic neurons both in human and experimental TSEs. PMID- 11214917 TI - Pathology of variant Creutzfeldt-Jakob disease. AB - Variant Creutzfeldt-Jakob disease (vCJD) is a novel prion disease in man which was first described in 1996 in the UK. There is substantial evidence to indicate that vCJD represents the effects of the bovine spongiform encephalopathy (BSE) agent in man. The neuropathology of vCJD is characterised by the florid plaque, composed of a central amyloid core with a fibrillary periphery, surrounded by a rim of spongiform change in an intact neuropil. Unique patterns of PrP accumulation in vCJD are revealed by immunocytochemistry in the cerebral and cerebellar cortices, the basal ganglia, thalamus and brainstem. The neuropathology of the thalamus and midbrain is also characterised by severe neuronal loss and gliosis. vCJD is distinct from other human prion diseases in that disease-associated PrP accumulates within follicular dendritic cells in lymphoid tissue, and consistently in peripheral sensory ganglia. All vCJD patients so far have been methionine homozygotes at codon 129 in the PrP gene. There is no evidence to indicate that cases of BSE infection have occurred in individuals in the UK who are MV or VV at codon 129 in the PrP gene. It is conceivable that BSE incubation periods in these groups may be longer than in methionine homozygotes, hence the precise numbers of future cases of vCJD are difficult to estimate at present. PMID- 11214918 TI - Clinical and differential diagnosis of Creutzfeldt-Jakob disease. AB - Until recently, the clinical diagnosis of CJD relied mainly on three criteria. These include patient history (rapidly progressive dementia), neurological findings (ataxia, pyramidal/extrapyramidal signs, myoclonus, akinetic mutism) and typical electroencephalographic (EEG) findings. These criteria are fulfilled in typical cases. The occurrence or increase of certain proteins in cerebrospinal fluid (CSF; 14-3-3, neuron-specific enolase) now provide important adjuncts in recognizing variant forms. Although these proteins can be detected in other neurological diseases accompanied with substantial brain damage such as encephalitis, they are also characterized by their high sensitivity and specificity with regard to other dementing processes (Alzheimer and vascular dementia). The increase in the number of positive cases during the last years in Germany reflects an improved case ascertainment rather than the appearance of the variant CJD (vCJD). Although several recent cases with a long duration of the disease were actually recognized, they did not reveal the typical florid plaques at autopsy. They were revealed as a rare variant of sporadic CJD, which is characterized by homocygosity for valine at codon 129 and PrP(Sc) type 1. This variant is positive for the 14-3-3 protein in CSF. Further subtypes described by Parchi et al. can also be characterized by a certain pattern of clinical symptomatology, EEG- and 14-3-3-findings. In addition, differential diagnosis revealed some treatable dementias among the most common diseases (Alzheimer and vascular dementia) such as herpes encephalitis, multiple sclerosis and Hashimoto encephalitis, particularly in the younger age group. PMID- 11214919 TI - Putting prions into focus: application of single molecule detection to the diagnosis of prion diseases. AB - Prion diseases are characterized by the cerebral deposition of an aggregated pathological isoform of the prion protein (PrP(Sc)) which constitutes the principal component of the transmissible agent termed prion. In order to develop a highly sensitive method for the detection of PrP(Sc) aggregates in biological samples such as cerebrospinal fluid (CSF), we used a method based on Fluorescence Correlation Spectroscopy (FCS), a technique which allows detection of single fluorescently labeled molecules in solution. Within the FCS setup, fluorescent photons emitted by molecules passing an open volume element defined by the beam of an excitation laser focussed into a diffraction-limited spot are imaged confocally onto a single photon counting detector. Aggregates of PrP(Sc) could be labeled by co-aggregation of probe molecules such as monomeric recombinant PrP or PrP-specific antibodies tagged with a fluorescent dye. In addition to slow diffusion, labeled aggregates are characterized by high fluorescence intensity, which allows detection and quantification by analysis of fluorescence intensity distribution. To improve detection of rare target particles, the accessible volume element was increased by scanning for intensely fluorescent targets (SIFT). To further improve sensitivity and specificity, two different probes were used simultaneously in a two-color setup. In a diagnostic model system of CSF spiked with purified prion rods, dual-color SIFT was more sensitive than Western blot analysis. In addition, a PrP(Sc)-specific signal was also detected in a number of CSF samples derived from CJD patients but not in controls. PMID- 11214920 TI - Detection of PrP(Sc) in subclinical BSE with the paraffin-embedded tissue (PET) blot. AB - The appearance of a new variant of CJD (vCJD) in young patients has caused considerable public concern and there is evidence that this novel disease is caused by the same agent as BSE. BSE is a prion disease that became epidemic in the UK, with a peak incidence in January 1993. New test systems should aim to identify BSE-infected cattle early in the incubation period. We compared the established histological and immunohistochemical methods and the Western blot method used by Prionics with the PET blot method that detects prion PrP(Sc) deposits in formalin-fixed and paraffin-embedded tissue. Investigating the obex region with the PET blot, all BSE cases were detectable and no false positive cases occurred. From the Swiss culling program, five clinically healthy cattle out of 1761 were identified as incubating BSE. With the PET blot method four of them showed the same PrP(Sc) deposition pattern that was seen in clinical BSE, though less conspicuous. In one of the five cases, PrP(Sc) was restricted to two brain stem nuclei, a pattern that was reported to be the first manifestation of PrP(Sc) deposits in the brain after peripheral infection and one that occurs after half of the incubation time. In this case, histology and Western blot were negative. PMID- 11214921 TI - Sheep and goats: natural and experimental TSEs and factors influencing incidence of disease. AB - The major factor influencing incidence of disease following challenge with transmissible spongiform encephalopathies (TSEs) in sheep is the allotype at amino acid numbers 136, 154 and 171 of the PrP protein. There are at least two groups of TSEs, one which targets the amino acid encoded at position 136 and the other which is more influenced by the amino acid at codon 171. Within these groups of TSE types, there may additionally be sub-types, as resistance to some, but not all, "136-type" TSEs can also be affected by the amino acid at codon 154. In goats, there are also PrP polymorphisms which apparently influence incubation period of TSE disease, however, this has not found to be true for cattle and BSE incidence. Sheep PrP amino acid codons 136, 154 and 171 do not explain everything about, for example, natural scrapie occurrence in sheep flocks, and attention is now turning to the flanking regions of the PrP gene looking for sequence differences in gene expression control motifs which may also have an influence on disease development. The sheep PrP gene produces two mRNAs in peripheral tissues, the result of alternative polyadenylation in the 3' untranslated region of the gene. Results from transfection assays of murine neuroblastoma cells with constructs expressing different regions of ovine PrP mRNA have revealed the presence of sequences in the 3' untranslated region that modulate protein synthesis and have therefore the potential to affect disease progression. PMID- 11214922 TI - Application of Prionics Western blotting procedure to screen for BSE in cattle regularly slaughtered at Swiss abattoirs. AB - Disease-specific PrP (PrP(Sc)) is at least part of the infectious particle (prion) causing bovine spongiform encephalopathy (BSE) or scrapie in sheep. Digestion with protease allows a distinction between normal PrP (PrP(C)) and PrP(Sc) i.e. PrP(C) is completely digested while PrP(Sc) is cleaved at the N terminus leading to a fragment of reduced molecular weight (PrP 27-30). Detection of this fragment by Western blotting has been described more than a decade ago for rodent PrP. We have now optimized the technique in order to allow rapid analysis of hundreds of samples per day. Here we report the application of this technique to the analysis of 3000 regularly slaughtered cattle from Swiss abattoirs. For comparison all the animals were subsequently examined by classical methods (i.e. histology and immunohistochemistry). All but one animal were negative for BSE by all methods. The Western blot positive animal was confirmed to be a BSE case and the carcass was removed from the food chain. We conclude that it is feasible to examine slaughtered cattle on a routine basis without causing delays to the meat processing industry. PMID- 11214923 TI - Specific determination of the proteinase K-resistant form of the prion protein using two-site immunometric assays. Application to the post-mortem diagnosis of BSE. AB - The aim of this work was to establish an immunological test suitable for specifically detecting PrPres in tissues from animals or humans developing TSEs. We chose to use as detection method a conventional two-site immunometric assay (sandwich immunoassay) because over the last 20 years this technique has clearly been shown to be more sensitive and specific than other tests. We have established numerous two-site immunometric assays based on the use of monoclonal antibodies and suitable for measurement of PrPsen in various mammalian species (human, bovine, ovine, mouse and hamster). A detection limit below 100 pg/ml was estimated from standard curves established using ovine recombinant PrP. PrPres was selectively detected by processing samples (currently brain homogenates) to enable specific purification and concentration of PrPres, which was finally solubilized by a strong denaturing treatment. This sample-processing procedure can be achieved within 30 minutes. The capacity of this test to detect bovine PrPres was estimated in the framework of an evaluation study organized by the Directorate-General XXIV of the European Commission during May 1999. On this occasion, a blind test on 1400 brain stem samples taken from either healthy (1000) or BSE-infected (300) cows demonstrated 100% sensitivity and specificity. In addition, dilution experiments showed that the test can significantly detect PrPres in homogenates diluted 1/300 and was at least as sensitive as a conventional bioassay performed on mice. PMID- 11214925 TI - Characterization of BSE and scrapie strains/isolates. AB - Following the BSE epidemic in cattle and the emergence of a variant form of Creutzfeldt-Jakob disease in humans, the question was raised whether BSE has been transmitted to small ruminants by the inadvertent feeding of infectious meat and bone meal. Such infections could easily be concealed in countries where scrapie is endemic. To address this issue by immuno-chemically analyzing the PrP(Sc) fragments, we have developed two lines of research. Firstly we have focused on the development of criteria for the differential characterization of experimental BSE and scrapie strains/isolates in rodents. To date, three criteria have been identified: quantification of the relative banding intensities of PrP(Sc) glycotypes using a photoimaging technique; the non-uniform kinetic of proteinase K degradation of PrP(Sc); and differences in the molecular masses of their non glycosylated PrP(Sc) fragments after PK cleavage in immunoblot. The second line of research focused on the implementation of the criteria described above to representative samples from scrapie diseased Irish sheep. Using these three criteria, no evidence was found for the presence of a BSE infection in these animals. However, the final conclusion must take into account the results of mouse incubation time and mouse lesion profile data which are currently being generated. PMID- 11214924 TI - PrP(Sc) typing by N-terminal sequencing and mass spectrometry. AB - The heterogeneity of the clinicopathological phenotype in human prion diseases is associated with the presence of the different forms of the abnormal prion protein, PrP(Sc). We have previously shown that PrP(Sc) in FFI and a subtype of familial CJD linked to the D178N mutation can be distinguished by their difference in gel mobility following proteinase K (PK) treatment. To further characterize the structural difference of PrP(Sc) in familial prion diseases, N terminal sequencing and mass spectrometry were used to identify the protease cleavage sites in PrP(Sc) extracted from affected brains. We found that the main PK cleavage sites of PrP(Sc) are located at residue 97 in FFI, and residue 82 in both CJD178 and a GSS subtype linked to the P102L mutation. The differential accessibility to protease in the native PrP(Sc) suggests that PrP(Sc) exist as distinct conformers in different disease states. PMID- 11214926 TI - Quantitative traits of prion strains are enciphered in the conformation of the prion protein. AB - Variations in prions, which cause different disease phenotypes, are often referred to as strains. Strains replicate with a high degree of fidelity, which demands a mechanism that can account for this phenomenon. Prion strains differ by qualitative characteristics such as clinical symptoms, brain pathology, topology of accumulated PrP(Sc), and Western blot patterns of glycosylated or deglycosylated PrP(Sc). Since none of these qualitative features can directly explain quantitative strain traits such as incubation time or dose response, we analyzed conformational parameters of PrP(Sc) and the rate of accumulation in different prion strains. Using the conformation-dependent immunoassay (CDI), we were able to discriminate among PrP(Sc) molecules from eight different prion strains propagated in Syrian hamsters. CDI quantifies PrP isoforms by simultaneously following antibody binding to both the denatured and native forms of a protein. In a plot of the ratio of antibody binding to denatured/native PrP graphed as a function of the concentration of PrP(Sc), each strain occupied a unique position, indicating that each strain accumulated different concentrations of particular PrP(Sc) conformers. This conclusion was supported by a unique pattern of equilibrium unfolding of PrP(Sc) found within each strain. By comparing the PrP(Sc) levels before and after limited proteinase K digestion, we found that each strain produces a substantial fraction of protease-sensitive PrP(Sc). We asked whether this fraction of PrP(Sc) might reflect those PrP(Sc) molecules that are most readily cleared by cellular proteases. When the protease sensitive PrP(Sc) fraction was plotted as a function of the incubation time, a linear relationship was found with an excellent correlation coefficient (r = 0.94). Combined with the data on time courses of prion infection in Tg(MHu2M) and Tg(SHaPrP) mice, the results argue that different incubation times of various prion strains may arise predominantly from distinct rates of PrP(Sc) clearance rather than from different rates of PrP(Sc) formation. PMID- 11214927 TI - Cellular and sub-cellular localisation of PrP in the lymphoreticular system of mice and sheep. AB - Using immunocytochemistry or immunogold electron microscopy, abnormal PrP accumulation was found in lymphoreticular tissues of Suffolk sheep naturally exposed to scrapie and in the spleens of ME7 infected C57 BL mice at 70 days after infection and at the terminal stage of disease at 170 days. Clinically diseased scrapie affected sheep show widespread PrP accumulation within tingible body macrophages (TBMs) and follicular dendritic cells (FDCs) of secondary lymphoid follicles. Serial tonsillar biopsies taken from 171 ARQ/ARQ sheep at 4 months of age did not contain abnormal PrP accumulations but 80% of biopsies were positive by 14 months. In contrast, whole body necropsies of sheep not previously biopsied failed to detect PrP in the tonsil of sheep at 4, 8, 12 or 16 months of age. These findings suggest that the biopsy procedure of susceptible sheep but not resistant sheep may induce tonsillar infection. In spleen of mice both at 70 and 170 dpi, accumulations of PrP were found within lysosomes of TBMs and also at the plasma-lemma of FDCs. In the light zone of follicles of terminally diseased mice, all FDC dendrites were arranged in the form of highly reactive or hyperplastic labrynthine glomerular complexes. PrP was consistently seen between FDC dendrites in association with abundant electron dense antigen-antibody complexes. At 70 days after challenge, labrynthine complexes were rare and invariably labelled for PrP. However, sparse PrP labelling was also seen on simple FDC dendrites at this stage. These observations suggests that scrapie infected FDCs continually release PrP from the cell surface where it accumulates in excess in association with trapped immune complexes and dendritic extension. It is likely that TBMs acquire lysosomal PrP following phagocytosis of effete FDC processes or from the extracellular space. We suggest that the normal function of PrP may involve cell process extension or immune complex trapping. PMID- 11214928 TI - Function of PrP(C) as a copper-binding protein at the synapse. AB - The prion protein (PrP(C)) shows cooperative copper binding of the N-terminal octarepeat (PHGGGWGO) x4. In brain homogenates, PrP(C) is found in highest concentration in synaptosomal fractions. Mice devoid of PrP(C) (Prnp0/0 mice) show synaptosomal copper concentrations diminished by 50% as compared to normal mice. PrP(C) in the synaptic cleft may serve as a copper buffer. Alternatively it may play a role in the re-uptake of copper into the presynapse or may be of structural importance for the N-terminus and thus may influence binding of PrP(C) to other proteins. PMID- 11214929 TI - The prion protein globular domain and disease-related mutants studied by molecular dynamics simulations. AB - In humans, familial forms of transmissible spongiform encephalopathies (TSE; "prion diseases") have been shown to segregate with the exchange of individual amino acids in the prion protein (PrP) sequence. We used the NMR structure of the globular domain of mouse PrP in the cellular form (PrP(C)) as a starting point for investigations by long-time molecular dynamics (MD) simulations at ambient temperature of likely impacts of such mutations on the PrP(C) structure, making use of the fact that species-related amino acid replacements between mouse PrP and human PrP are spatially well separated from the disease-related mutations in human PrP. In the MD simulations these amino acid substitutions were found to have a variety of different effects on the protein structure, with some species showing altered packing of regular secondary structure elements, while other mutants showed no or only strictly localized changes of the structure near the variant amino acid. The fact that some of the disease-related amino acid exchanges cause no measurable change of the PrP(C) structure indicates that their influence on the conformational transition to the scrapie form of PrP may be due to modified intermolecular interactions during the aggregation process. PMID- 11214930 TI - Neurotoxicity but not infectivity of prion proteins can be induced reversibly in vitro. AB - Prion diseases include Creutzfeldt-Jakob disease in humans, scrapie in sheep and bovine spongiform encephalopathy. The hallmark of prion diseases is the accumulation of an abnormal isoform (PrP(Sc)) of the cellular prion protein accompanied by neuronal cell death and astroglial proliferation. To characterize the correlation between PrP secondary and quarternary structure and their biological effects we assayed soluble and aggregated forms of PrP 27-30, the N terminal truncated form of PrP(Sc), as well as the corresponding recombinant PrP(90-231) for their neurotoxicity and infectivity. PrP was kept soluble in 0.2% SDS and subsequently re-aggregated either by diluting the SDS or by adding acetonitril. The neurotoxicity of the re-aggregated states were comparable to that of prion rods (PrP 27-30) whereas the soluble forms had no neurotoxic effects. The solubilized PrP 27-30 showed no significant infection upon re aggregation as determined by bioassays in Syrian golden hamsters. The recombinant PrP did not exhibit infectivity in any state. PMID- 11214932 TI - The use of monoclonal antibody epitopes for tagging PrP in conversion experiments. AB - The key event in the pathogenesis of spongiform encephalopathies is a conformational transition of a normal cellular protein, PrPsen, to its pathological isoform, PrPres. The mechanism of PrPres formation is unknown but is likely to involve a direct interaction between PrPsen and PrPres. The molecular basis of PrPres formation has been studied extensively using transgenic mice and scrapie-infected tissue cultures that express heterologous PrP molecules. However, these experiments are dependant on the discrimination of endogenous host PrP and exogenous PrP molecules. Here we give a short review on the PrP-specific epitopes that have been used for tagging exogenous PrP molecules and present a novel PrP-specific epitope that is well suitable for in vivo and in vitro conversion experiments. PMID- 11214931 TI - Inhibition of formation of protease-resistant prion protein by Trypan Blue, Sirius Red and other Congo Red analogs. AB - Five compounds related to Congo Red were found to inhibit generation of protease resistant prion protein in a cell-free system. In this assay Trypan Blue, Evans Blue, Sirius Red F3B, Primuline and Thioflavin-S were all more inhibitory than Congo Red itself. In scrapie-infected mouse neuroblastoma cells one compound, Sirius Red F3B, was capable of blocking the formation of protease-resistant prion protein to a similar extent as Congo Red; however, the other four compounds were less effective. Some of these compounds should be considered for testing in TSE disease models in live animals. PMID- 11214933 TI - Prions: from neurografts to neuroinvasion. AB - Spongiform encephalopathies are infectious neurodegenerative diseases caused by pathogens that seem to be devoid of any informational nucleic acids. Histopathologically, these diseases are characterized by spongiform degeneration of the central nervous system. Although the main pathological changes during the course of the disease occur in the brain, the infectious agent accumulates early in lymphoid tissue. The consecutive development of clinical disease depends on the presence of an intact immune system including mature B-cells and follicular dendritic cells. In this article we review the state of knowledge on the routes of neuroinvasion used by the infectious agent in order to gain access to the central nervous system upon entry into extracerebral sites. PMID- 11214935 TI - Pathogenesis of natural scrapie in sheep. AB - Although scrapie has been known for a long time as a natural disease of sheep and goats, the pathogenesis in its natural host still remains unclear. To study the pathogenesis of natural scrapie, we used immunohistochemistry to monitor the deposition of PrP(Sc) in various tissues, collected during a natural scrapie infection from sheep with the PrP(VRQ)/PrP(VRQ) genotype which were purposely bred for their short incubation period for natural scrapie. PrP(Sc) was present in the lymphoid tissues of all animals from the age of 5 months onwards. At this age, PrP(Sc) was detected in the neural tissues only in the enteric nervous system (ENS) at the level of the duodenum and ileum. At the age of 10 months, PrP(Sc) was not only found in the ENS but also in the ganglion mesentericum cranialis/coeliacum, the dorsal motor nucleus of the vagus, and the intermediolateral column of the thoracic segments T8-T10. PrP(Sc) was detected for the first time in the nucleus tractus solitarius and ganglion nodosus at 17 months of age and in the ganglion trigeminale and several spinal ganglia at 21 months of age. Since the scrapie agent consists largely, if not entirely of PrP(Sc), these results indicate that the ENS acts as a portal of entry to the neural tissues for the scrapie agent followed by centripetal and retrograde spread through sympathetic and parasympathetic efferent fibers of the autonomic nervous system to the spinal cord and medulla oblongata respectively. PrP(Sc) accumulation in sensory ganglia occurs after infection of the CNS and is therefore probably due to centrifugal and anterograde spread of the scrapie agent from the CNS through afferent nerve fibers. PMID- 11214934 TI - Pharmacological manipulation of early PrPres accumulation in the spleen of scrapie-infected mice. AB - In most experimental models of scrapie and in some naturally infected species, the lymphoreticular system and the spleen in particular play a major role in the pathogenesis of the disease. Previous studies demonstrated scrapie infectivity in peripheral organs from the day of infection up to the terminal stage. The discovery of the abnormal prion protein, PrPres, as a specific molecular hallmark of scrapie should permit enhanced study of scrapie pathogenesis and has some pharmacological applications. In this study, PrPres accumulation was followed day by day in peripheral organs. Four different phases were identified: the circulation of scrapie inoculum, a clearance phase, the peripheral accumulation of PrPres and a plateau phase. This kinetics was then pharmacologically modified (i) by applying the macrophage "suicide" technique to unveil the cellular types involved in scrapie pathogenesis and (ii) with anti-scrapie drugs such as polyene antibiotics, polyanions and Congo red to investigate their mode and site of action. PMID- 11214936 TI - Detection of cattle-derived BSE prions using transgenic mice overexpressing bovine PrP(C). AB - In interspecies transmissions of transmissible spongiform encephalopathies, the agent has to overcome a species barrier that is largely influenced by the rate of homology between the prion proteins (PrP(C)) of the two involved species. Generating transgenic mice expressing PrP(C) of a foreign species is an approach to develop TSE models that are at least partly devoid of a species barrier. The availability of such animals would enable the detection of low doses of infectivity in tissues or bodily fluids derived from other species. We generated transgenic mice that overexpress bovine PrP(C) (Tgbov XV mice) for the development of an improved detection assay for cattle derived BSE prions. These mice succumbed to the disease 250 days after inoculation with a brain homogenate from BSE diseased cattle. Diagnosis of BSE in transgenic mice was confirmed using Western blot, as well as histological and immunohistochemical methods. In contrast, transgenic mice overexpressing murine PrP(C) (tga20 mice) did not display shorter incubation times than nontransgenic RIII mice infected with the same inoculum. The expression of a chimaeric PrP of murine and bovine sequences rendered such mice partly, if not entirely resistant to an infection with the BSE agent. PMID- 11214937 TI - Analyzing the influence of PrP primary structure on prion pathogenesis in transgenic mice. AB - Expression of prion protein (PrP) genes in transgenic (Tg) mice has been an extremely effective means of studying human and animal prion diseases. Indeed, much of what we currently understand about the molecular basis of prion pathogenesis derives from such studies. Despite these advances, the emergence of a new variant of Creutzfeldt-Jakob disease (vCJD), apparently the human manifestation of bovine spongiform encephalopathy (BSE), demonstrates that our understanding of the factors controlling prion transmission is far from complete. We review studies in Tg mice that have addressed issues of prion strains and species barriers and have provided insights into mechanisms of prion propagation. The goal of future investigation will be to determine the interplay between PrP primary structure and conformation in determining prion transmission barriers and we discuss some ongoing transgenic studies designed to address these issues. PMID- 11214938 TI - A single amino acid alteration in murine PrP dramatically alters TSE incubation time. AB - In order to investigate mutations linked to human TSEs, we have used the technique of gene targeting to introduce specific mutations into the endogenous murine PrP gene which resulted in a P101L substitution (Prnp(a101L)) in the murine PrP gene. This mutation is equivalent to the 102L mutation in the human PrP gene which is associated with Gerstmann-Straussler syndrome. Since the mutated gene is in the correct chromosomal location and control of the mutant gene expression is identical to that of the wild type murine PrP gene, the precise effect of the 101L mutation in the uninfected and TSE infected mouse can be investigated in this transgenic model. Mice homozygous for this mutation (101LL) while showing no spontaneous TSE disease were more susceptible to TSE disease than wild type mice following inoculation with GSS infectivity. Disease was transmitted from these mice to mice both with and without the Prnp(a101L) allele. The 101L mutation does not therefore produce spontaneous genetic disease in mice but does dramatically alter incubation periods following TSE infection. Additionally, a rapid TSE transmission was demonstrated associated with extremely low amounts of PrP(Sc). PMID- 11214939 TI - Homocysteine and human reproduction. AB - Homocysteine is an amino acid that is capable of disturbing the proper growth of cells. Hyperhomocysteinemia can lead to a non-closure of the neural tube. The underlying basis is a derangement of homocysteine metabolism due to a missense mutation of the MTHFR enzyme that has to catalyze the folate metabolic cycle furnishing sufficient methyl groups for DNA and tRNA synthesis. Folate can overcome the dysfunction of the mutation and the decreased activity of the thermolabile MTHFR. Homocysteine is also recognized as an independent risk factor for obstetrical vascular disease that can manifest itself in maternal veins (thrombosis), arteries (preeclampsia) or spiral arteries supplying the placenta (placental abruption). Low vitamin status (folic acid, vitamin B6 and B12), hyperhomocysteinemia, the MTHFR gene mutation C677T, and thrombotic factors like Protein C, Protein S. antithrombin III, factor V Leiden and Activated Protein C, are alone or in combination high risk factors for obstetrical vascular disease. Their values can be modulated by B-vitamin status and could be able to prevent disease from occurring or recurring. Placebo-randomized trials have been done in neural tube defects but are urgently needed in the vascular area. The common denominator of the effect of homocysteine on the embryo and the blood vessels (endothelium) could be sited in the process of proliferation of cells that need proper methyl groups for proper function. PMID- 11214940 TI - The presence of small uterine fibroids not distorting the endometrial cavity does not adversely affect conception outcome following embryo transfer in older recipients. AB - PURPOSE: To determine if uterine fibroids have a negative impact in older patients having embryo transfer (ET). METHODS: Comparison of clinical and viable pregnancy rates, implantation rates, and spontaneous abortion rates in older (>35) oocyte or embryo recipients with uterine leiomyomata compared to comparable patients without fibroids. RESULTS: The clinical pregnancy rate per transfer was 56% in the fibroid group vs 64% for the controls. Implantation rates were also very similar (33 vs 32%7). There were no spontaneous abortion or preterm deliveries <32 weeks in the fibroid group and the average term of pregnancies was also similar. CONCLUSION: Small fibroids not distorting the uterine cavity do not seem to negatively affect conception outcome even in older women. PMID- 11214941 TI - Successful pregnancy despite advanced age and elevated serum follicle stimulating hormone levels--a case report. AB - PURPOSE: To determine if a woman over age 45 with elevated serum follicle stimulating hormone (FSH) levels in the early follicular phase could still successfully conceive. METHODS: Female partner was treated with guaifenesin to improve cervical mucus quality and vaginal progesterone in the luteal phase. Careful monitoring of follicular maturation was performed. RESULTS: A successful pregnancy after 14 months of progesterone therapy was achieved. CONCLUSIONS: It is possible for a 46-year-old infertile woman with elevated serum FSH to achieve a pregnancy even when the male partner is taking calcium channel blockers for heart problems. PMID- 11214942 TI - Comparable implantation rates with fresh vs frozen embryo transfer suggests that controlled ovarian hyperstimulation has an adverse effect on conception outcome. AB - PURPOSE: A retrospective comparison of fresh vs frozen embryo pregnancy rates. METHODS: All frozen embryos transferred used in the analysis including deselected embryos from the oocyte retrieval cycle, and twice-frozen embryos. RESULTS: Pregnancy and implantation rates following fresh or frozen embryo transfers were similar. CONCLUSION: The similar outcomes despite the obvious disadvantages for the frozen-thawed embryo suggests that some other factor reduces the chance of embryo implantation on oocyte-retrieval cycles. An adverse affect of controlled ovarian hyperstimulation on the uterine environment is a strong possibility. PMID- 11214943 TI - A morphologic and morphometric study of the vesical mucosa and urethra of castrated female rats following estrogen and/or progestogen replacement. AB - PURPOSE: The aim of this study was to analyze the morphologic and morphometric changes in the urethra and vesical mucosa following hormonal replacement METHODS: We analyzed the changes in the urethra and vesical mucosa of 35 castrated adult female rats that had been subjected to estrogen and/or progestogen replacement. RESULTS: Estrogen replacement, whether or not accompanied with progestogen replacement, provoked metaplasia, hyperplasia and an increased occurrence of stratified epithelia. In the proximal urethra hypoestrogenism caused a higher occurrence of pseudo-stratified and transition epithelia, whereas in the urethral vesical junction it caused a higher frequency of pseudo-stratified epithelia. The thickness of the epithelium increased following estrogen replacement whereas only a trend towards an increase of the propria lamina thickness was identified. Nuclear volume was only altered in the bladder epithelium. CONCLUSION: Estrogen replacement acted both morphometrically and morphologically on the lower urinary tract. PMID- 11214944 TI - Additive antioxidative effect of hormone replacement therapy combined with a statin. AB - In treating postmenopausal women both statins and estrogens have been shown to elicit favourable effects on lipids and lipoproteins. In addition direct beneficial effects of these substances on the vascular wall are discussed. However, progestin addition to estrogen replacement therapy, which is mandatory in women with an intact uterus. is thought to deteriorate at least partly estradiol-induced direct effects on the vasculature. Oxidation of LDL, which mainly takes place in the vessel wall, seems to be a crucial step in the development of atherosclerosis. Therefore, for the first time, the effect of a statin and an estrogen/progestin combination on the in vitro oxidation of human LDL was investigated comparing the monosubstances fluvastatin. 17beta-estradiol and norethisterone acetate (NETA) as well as the effect of the combination. LDL was isolated from human female serum and oxidation was initiated by copper(II) chloride. The progression of LDL oxidation was monitored spectrometrically at 234 nm for 300 min. Fluvastatin significantly delayed the onset of LDL oxidation (controls = 85 min) by 21 min at 1 microM, by 99 min and by 210 min at 5 and 10 microM. respectively. 17beta-estradiol significantly reduced the onset by 73 min at 1 microM and by more than 300 min at 5 and 10 microM. NETA had no significant effect. The combination of I microM 17beta-estradiol and 1 microM fluvastatin with 1, 5 and 10 microM NETA showed an additive antioxidative effect of estradiol and fluvastatin and no deterioration by the addition of NETA even at high dosages. It can be concluded that treatment of postmenopausal women with fluvastatin and a combination of 17beta-estradiol with NETA may have not only beneficial effects on lipid disorders but may also elicit a direct potent antiatherosclerotic action on the vasculature. PMID- 11214945 TI - Adrenalin versus terlipressin: blood loss and cardiovascular side-effects in the vaginal part of laparoscopically-assisted vaginal hysterectomy or vaginal hysterectomy. AB - The purpose of the study was to compare blood loss and cardiovascular side effects in the course of the vaginal part of laparoscopically-assisted vaginal hysterectomy (LAVH) or single vaginal hysterectomy (VH) [1]. Blood loss was evaluated in relation to local application of two haemostatic agents, e.g. adrenalin as a gold standard versus terlipressin. The investigation was designed as a prospective randomised study. A prospective group of 40 patients selected for LAVH or VH was randomised into two groups, e.g. 20 patients in each group. In both of these groups, the blindly selected haemostatic agent was applied locally immediately before circular colpotomy, the surgeon not being aware which agent was being used. Because of the claimed delayed effect of terlipressin a third group of another 20 patients was randomly selected. For comparison in this group terlipressin was locally already applied before the laparoscopic part of LAVH, e.g. 20-25 minutes before performing circular colpotomy. Thus, this particular group could not be made blind to the surgeon. The study confirmed a significantly superior haemostatic effect of adrenalin. On the other hand after the adrenalin application a higher frequency of hypertensive reactions and mild arrythmias were observed but without any clinical seguelae. PMID- 11214946 TI - At term pregnancies in transfusion-dependent beta-thalassemic women. AB - The health background management and outcome of five pregnancies in women affected by Cooley Disease are described and the preconceptual guidance and care are considered. The patients were selected from a group of 103 thalassemic women divided into three subgroups according to their first and successive menstruation characteristics. Only one woman needed induction of ovulation. A precise and detailed pre-pregnancy assessment was done before each conception. All the women were in labour at 38 weeks' gestation, and five healthy babies were born at term, weighing between 2,600 and 3,200 g. The improvement in current treatments will result in a continuous increase in pregnancies in thalassemic women, making pregnancy a real eventuality for them. Furthermore, we are studying the possibility of collecting foetus umbilical cord blood after delivery, with the aim of obtaining complete marrow reconstitution in an attempt at heterologous transplantation to the mother. PMID- 11214947 TI - Homocysteinaemia during pregnancy and placental disease. AB - OBJECTIVE: Hyperhomocysteinaemia, due to enzymatic defects or to the lack of some vitamin cofactors (vit. B6, vit. B12, folic acid), could be associated with obstetric disease. The aim of this study was to investigate placental disease in women with mild-moderate hyperhomocysteinaemia. MATERIALS AND METHODS: Blood samples of seven pregnant women with severe early onset preeclampsia were assessed for hyperhomocysteinaemia. The obtained values were compared with those of a control group. In all cases, tissue samples obtained from the placenta, umbilical cord and membranes were studied. One of the patients was treated empirically with folic acid during a subsequent pregnancy. RESULTS: Patient homocysteine plasma levels were higher than in the control group. In all cases several placental abnormalities were found. The patient treated with folic acid had a good pregnancy outcome. CONCLUSION: Hyperhomocysteinaemia during pregnancy could be responsible for placental abnormalities. Treatment with folic acid could improve pregnancy outcome in women with homocysteine metabolism abnormalities. PMID- 11214948 TI - Infertility treatment by in vitro fertilization in patients with minimal or mild endometriosis. AB - PURPOSE: To estimate the clinical effectiveness of in vitro fertilization treatment in patients with minimal or mild endometriosis (stages I and II) in comparison to the patients with tubal infertility in terms of fertilization, pregnancy and livebirth rates. METHODS: Retrospective analysis of the outcome of IVF-ET in 612 cycles of the patients with endometriosis (389 stimulated with HMG/HCG and 223 co-treated with GnRH-a) and in 7,339 cycles of the patients with tubal infertility (5,520 stimulated with HMG/HCG and 1,819 co-treated with GnRH a). RESULLTS: Regardless of the type of ovarian stimulation, the fertilization rate per treated cycle was practically the same in both groups (endometriosis 81.4% vs tubal infertility 84.2%; p = 0.07). However, in the endometriosis group the pregnancy rate was higher (25.3% vs 18.9%; p = 0.000), and so was the livebirth rate (19.0% vs 14.2%; p = 0.003). Considering the type of ovarian stimulation, the fertilization rate in the endometriosis group was almost the same in the HMG/HCG (81.2%) and in the GnRH-a co-treated cycles (81.6%), and did not differ from that in the tubal infertility group (83.6% in the HMG/HCG vs 85.9% in the GnRH-a cycles). In the GnRH-a co-treated cycles the pregnancy rate and the livebirth rate were not significantly higher in the endometriosis group than in the tubal infertility group (27% and 20.2% vs 22.2% and 17.5%). In the HMG/HCG stimulated cycles the pregnancy rate was significantly higher in the endometriosis than in the tubal infertility group (24.3% vs 17.7%; p = 0.004), and so was the livebirth rate (18.4% vs 13.0%; p = 0.008). CONCLUSION: In patients with minimal or mild endometriosis the IVF-ET procedure is at least as effective as in patients with tubal infertility. PMID- 11214949 TI - Multiple ovarian biopsy in the treatment of women with polycystic ovary syndrome (PCOS). AB - BACKGROUND: Ovarian electrocautery has been used with success in the treatment of PCOS women. However, unipolar coagulation carries the risk of serious injuries to pelvic organs. In an effort to avoid this potential risk, the efficacy of multiple ovarian biopsy was evaluated in our study. METHODS: Eleven PCOS patients were enrolled to the study. Four to eight biopsies were taken from both ovaries. The levels of LH, FSH, androgens and the reactivity of ACTH test were evaluated at standard intervals. The occurrence of ovulation was determined by ultrasound. RESULTS: Laparoscopy was followed by non-significant changes of endocrine parameters only. The ovulatory cycle was restored in only three women of the whole group. CONCLUSIONS: Our study did not prove the efficacy of multiple ovarian biopsy in the treatment of PCOS women. The procedure caused only minor changes in endocrine parameters and rarely restored ovulation. PMID- 11214950 TI - The emergency department gynaecologist and emergency postcoital contraception. AB - The emergency department gynaecologist is often faced with requests for emergency postcoital contraception. The physician on duty is usually very busy and does not always have enough time to perform a complete evaluation of the woman's state of health. The emergency gynaecologist who prescribes postcoital contraception also has a number of other problems to cope with in regard to the pharmacological preparations on the market, the efficacy of various methods, the monitoring of side-effects which are not, always, tolerated by all patients and the outcome of his therapeutic prescription. All these aspects should be emphasized in the "first aid" counselling offered to the patients. In conclusion, we consider that any women who decides to use postcoital contraception should have the right to receive assistance of guaranteed quality throughout the period that elapses between taking the drug and the subsequent menstrual cycle. This is not strictly guaranteed by an emergency gynaecological service. PMID- 11214951 TI - Ureteral drainage by double-J-catheters during pregnancy. AB - PURPOSE: To access the safety and effectiveness of Double-J-stents in treating symptomatic hydronephrosis during pregnancy. MATERIAL AND METHODS: From 1994 to 1999, 21 women were hospitalized in the Urology Clinic at the University Hospital of Crete. Fourteen patients presented acute pyelonephritis, six painful hydronephrosis and one spontaneous renal rupture. In four cases the hydronephrosis was caused by calculus in the upper 3rd quadrant of the ureters. In 13 out of 14 cases of urinary febrile infection and one with spontaneous renal rupture, the dilatation resulted from direct compression of the ureters by the gravid uterus. Using ultrasound guidance, 21 ureteral stents were successfully placed under local ane- sthesia. RESULTS: In 14 out of 21 patients with urinary infection, we observed remission of fever during the first 24 hours after the placement of the ureteral stents. In the patient with spontaneous renal rupture the remission of symptoms was observed a few hours after the ureteral drainage. Complications were reported in six cases, such as, voiding symptoms and discomfort. CONCLUSION: Double-J-ureteral stenting is an effective, simple and safe method in treating symptomatic hydronephrosis during pregnancy. PMID- 11214952 TI - A comparative study of a gonadotropin-releasing hormone agonist and finasteride on idiopathic hirsutism. AB - OBJECTIVE: To compare the efficacy of finasteride and GnRH agonist in the treatment of idiopathic hirsutism. METHODS: Sixty women with hirsutism were randomly assigned to receive either 5 mg of finasteride or long-acting GnRH agonist (depot leuprolide 3.75 mg) intramuscularly monthly for six months. MAIN OUTCOME MEASURES: Hirsutism scores were measured according to the Ferriman Gallway scoring system, and side-effects were monitored for six months of treatment. Blood samples were taken at each visit for assessment of endocrine (FSH, LH, estradiol, progesterone, total and free testosterone, androstenedione, DHEAS-S, 17-OH-P. SHBG), biochemical, and hematologic para- meters. RESULTS: All of the patients treated with finasteride or GnRH agonist showed neither menstrual abnormalities nor side-effects. The mean percent change (+/- SD) in hirsutism scores in the GnRH and finasteride groups was 36% +/- 14% and 14% +/- 11% at six months, respectively. Serum total testosterone, free testosterone, androstenedion and DHEA-S showed a meaningful decrease in patients treated with GnRH agonist. On the other hand, only serum total testosterone and free testosterone levels decreased with finasteride treatment (p < 0.05 and p < 0.0001, respectively). PMID- 11214953 TI - The evaluation of misoprostol-related tachysystole in normal and high risk pregnancies. AB - OBJECTIVE: To determine whether misoprostol-related tachysystole is due to the cumulative effect of the drug. METHODS: A group of preeclamptic patients were chosen and data were compared to non-preeclamptic patients to prove the hypothesis. Among 90 patients evaluated, 45 were preeclamptic while 45 were non preeclamptic. Six out of 43 preeclamptic patients were diagnosed as having HELLP syndrome. All patients were induced by 50 microg of misoprostol applied to the posterior vaginal fornix with 4-hour intervals for a maximum of three times. RESULTS: Two patients from both groups were left out of the study leaving 86 patients to evaluate. The number of misoprostol tablets used in the preeclamptic group was significantly higher (2.32 +/- 0.64 preeclamptic vs 1.81 +/- 0.76 tablets non-preeclamptic group; [p = 0.001]) while the number of women giving birth after only one tablet of misoprostol was significantly lower (2/24 preeclamptic vs. 14/32 non-preeclamptic group [p = 0.006, OR 0.116; 95% CI 0.02 0.58]). Although the frequency of tachysytolic patterns observed was different between the two groups, (35% preeclamptic vs 16% non-preeclamptic) this difference was not statistically significant (p = 0.082). It is important to note that an increase of only one case having tachysystole in the preeclamptic group would have converted this difference to significant. CONCLUSION: Relatively hard induction of labor in preeclamptic patients leads to an increase in the amount of misoprostol used and hence to an increased incidence of tachysystole secondary to the cumulative effect of the drug. These findings seem to support our hypothesis and prove the presence of the cumulative effect of misoprostol. PMID- 11214954 TI - Changes of glucose tolerance after delivery in women with gestational diabetes. AB - We investigated glucose tolerance after cesarean section in 24 women with gestational-onset diabetes (group A), in 18 women with an adverse pregnancy outcome (group B), and in 19 healthy pregnant women (group C). Glucose tolerance was performed within six days as well as six weeks after delivery. Eleven (45.8%) women in group A, five (27.8%) in group B and one (5.2%) in group C showed glucose intolerance immediately after delivery. Six weeks after delivery, 18 (75%) women in group. A showed normal glucose tolerance (NGT), four (16.6%) impaired glucose tolerance (IGT) and two (8.3%) diabetes according to WHO criteria. NGT showed 16 (88.8%) women in group B, and 19 (100%) in group C, while two (11.1%) women in group B presented with IGT. We conclude that a glucose tolerance test both immediately and six weeks after delivery is useful not only in women who have gestational diabetes but also in women with an adverse pregnancy outcome. PMID- 11214955 TI - Pseudoxanthoma elasticum and pregnancy: a case report. AB - BACKGROUND: Pseudoxanthoma elasticum (PXE) is a rare hereditary disease characterised by systemic degeneration of elastic tissue. Calcification of elastic fibres seen histologically is pathognomonic for the disorder. Most pseudoxanthoma elasticum patients show no serious complications during pregnancy. CASE: We report a case of a 29-year-old white woman with pseudoxanthoma elasticum, who delivered a healthy infant at the 35th week by cesarean section after an uneventful pregnancy. Sonographic and histological placental findings are described. CONCLUSION: Pregnancy in a patient with pseudoxanthoma elasticum presents some problems such as the evolution of the disease in the soon to be mother and the influence of the disease on the pregnancy. In our case there were no fetal-maternal complications related to the disease except skin lesion aggravation. PMID- 11214956 TI - Effects of unilateral uterine artery ligation on skin development. AB - BACKGROUND: It has been previously demonstrated that intrauterine growth retardation (IUGR) due to vascular insufficiency in humans results in newborn infants with marked loss of subcutaneous fat and decreased content of differentiation-specific epidermal structural proteins. OBJECTIVE: In this study, the teratogenic effects of impaired maternal blood flow were investigated histologically on rat skin. MATERIALS & METHODS: Twenty Spraque-Dawley female rats were separated into two groups (n = 10), a control (sham-operated) and an experimental group. The experimental group of fetal rats were subjected to IUGR by unilateral ligation of the maternal uterine artery on the 18th day of pregnancy. The maternal rats were subjected to cesarean hysterectomy on the 21st day of pregnancy and a skin biopsy was taken from the respective litters of both groups. RESULTS: In histopathological examination, normal epidermis and dermis were observed in the control group of litters and littermate rats from the opposite uterine horn (non-ligated side). A statistically significant reduced body weight and height were noted in the ligated side of the litters. CONCLUSION: Our findings give further evidence to the concept that normal maternal blood flow is essential for fetal growth and decreased maternal blood flow may create an impairment in skin development. PMID- 11214957 TI - Misoprostol in uterine atony: a report of 2 cases. PMID- 11214958 TI - Eighteen years of maternity care in a new teaching hospital. AB - A new maternity hospital was inaugurated in Trinidad in 1981 to provide access for pregnant women to specialist antenatal care and to trained attendants during childbirth. As an academic tertiary-care institution, it also became a referral centre for high-risk pregnancies and obstetric emergencies. The efficacy of the services provided since inception was evaluated by measurement of mortality statistics, which are the most sensitive indices of maternal care. Over a period of 18 years, there were almost 100,000 births. Although the caesarean section rate was low, the perinatal and maternal mortality rates suggest that there is still a wide gap in obstetric standards between the developed world and this country. Improved vigilance for high-risk groups is required to identify potentially preventable deaths. PMID- 11214959 TI - Fetal echocardiography: a comparison of different techniques. AB - There is great availability on the market of echocardiographic instruments that have innovative technological systems which use second harmonic imaging. The true usefulness and applicability of these instruments in fetal echocardiography have yet to be verified. The objective of the present study was to verify the impact of this echographic technology in the diagnostic evaluation of the fetal cardiovascular system. Thus, an Acuson Sequoia echograph which uses native tissue harmonic imaging (NTHI) was used to examine 30 pregnant women between the 28th and 32nd week of gestation. The b-mode and m-mode images were acquired and recorded by the conventional method and by the second harmonic imaging method without contrast medium. Two experts in the field analyzed and compared the images recorded by the two methods and made diagnostic and qualitative judgements. The 30 cases examined were unanimously determined to have no visible echo pathologies. The morpho-biometric evaluation obtained by the two methods did not show any significant differences and the quality of the images obtained by the traditional method was found on average to be higher. In conclusion we believe that the use of second harmonic imaging for studies of the fetal heart does not seem to offer any advantages with respect to the conventional method. PMID- 11214960 TI - Hepatic and renal effects of azidothymidine and acyclovir on pregnant rats. AB - The antiviral effect of azidothymidine (AZT) can be potentiated by acyclovir (ACV), and this drug association has been used in the management of HIV-infected patients. In the present study we examined the effects of this association on the livers and kidneys of both pregnant rats and their concepts. Previous data from this laboratory suggested that the deleterious effects of ACV on rat pregnancy are due to its extraplacental actions and these are, at least in part, counteracted by concomitant treatment with AZT. Kidneys and livers of pregnant rats were noticed to be much more sensitive to the toxic action of the drugs than those of their concepts, ACV eliciting much more evident morphological alterations than did AZT. Contrary to what was expected, in the group of rats treated with both drugs AZT was not able to diminish the severity of the alterations evoked by ACV. The proposed "protective" action of AZT against the abortive effect of ACV on rat pregnancy does not seem to be exerted through a renal or hepatic pathway. PMID- 11214961 TI - The effects of sialoadenectomy & flutamide on skin development. AB - BACKGROUND: Epidermal growth factor is a low molecular weight polypeptide with 53 amino acids and is known to stimulate cell proliferation and differentiation in a wide range of tissues. The submandibulary gland in the mouse is a rich source of epidermal growth factor and decreased plasma epidermal growth factor levels have been observed after sialoadenectomy (removal of the submandibular glands). Furthermore. there is evidence that epidermal growth factor stimulates spermatogenesis and reverses antiandrogen induced cryptorchidism. OBJECTIVE: In the present study, the teratogenic effects of sialoadenectomy and antiandrogen (flutamide) administration on rat skin were investigated histologically. MATERIALS & METHODS: Thirty Spraque-Dawley female rats were separated into three groups (n = 10), a control (sham-operated) and two experimental groups. The first experimental group of rats were subjected to sialoadenectomy in order to create maternal EGF deficiency one month before copulation. The second experimental group of rats were given flutamide (10 mg/100 g) for ten days during pregnancy. Three months after birth, a penile skin biopsy was taken from respective offspring in all groups. RESULTS: A statistically significant reduced body weight and length were noted in the first group of litters (maternal EGF deficient) and in the flutamide administered group when compared to the control group. Atrophic epidermis and dermal adnexa were observed histologically as the teratogenic effects of sialoadenectomy and flutamide administration on rat skin development. CONCLUSION: Epidermal growth factor is a key hormone for skin development and antiandrogen administration may insult this process by interfering with epidermal growth factor metabolism. PMID- 11214962 TI - Teratogenic effects of propineb on rat skin. AB - The dithiocarbamates are known to cause dermatitis, conjunctivitis, rhinitis, pharyngitis and bronchitis in humans. The experimental group received Propineb (obtained from Bayer) concentrations of 400 ppm in distilled water five days a week (treatment time three weeks) administered orally by gasric pit. Acute oral LD50 for male rats has been found to be 8,500 mg/kg (Worthing, 1983). The control group (n = 10) received only distilled water. At ultrasonographical examination, there were no resorbed fetuses or stillborns during or after propineb administration. It can be clearly seen that the body weights of the experimental group of litters are lower than those of the control group (p < 0.001). However, the mean length of the experimental litters was identical to the control group of litters (p > 0.05). Under microscopical examination, increased keratinization and hyperplasia were observed in the epidermal cells. PMID- 11214963 TI - Effects of clomiphene citrate on neonatal rat skin. AB - BACKGROUND: Clomiphene citrate is chemically related to non-steroidal estrogens, and has antiestrogenic properties. It is used in the treatment of anovulatory female infertility and its therapeutic effect mainly depends on inhibiting the negative feedback effects of endogenous estrogen by stimulating the gonadotropin releasing hormone. Today, it is also used in the treatment of male infertility. OBJECTIVES: In this study the effects of clomiphene citrate on skin maturation in neonatal rats were investigated. METHODS: Forty Spraque-Dawley female newborn rats were separated into two control and two experimental groups (n = 10). One day after birth. experimental newborn rats were given clomphene citrate subcutaneously in a dosage of 100 mg/kg/day for five days. The first experimental group of rats were anesthetised at 21 days whereas the second experimental group of rats were then anestetised on day 28. Biopsies were taken immediately from the perineal skin. Histopathological assessments were made and compared with their control groups. RESULTS: In both the experimental groups of newborn rats, increased keratinization and irregular hypertrophy were observed in the epidermal cells. Disorganization of the basal layer cells and hyperplasia were found to be more prominent in the first experimental group and dermal fibrosis and lymphohistiocytic inflammatory cell infiltration were especially prominent around the sebaceous glands in the second experimental group. CONCLUSION: The administration of clomiphene citrate in newborn rats showed impaired skin maturation. PMID- 11214964 TI - Teratogenic effects of nicotine on rat skin. AB - BACKGROUND: Nicotine is a well-known toxic alkaloid substance with several teratogenic effects. In animal studies it has been observed that nicotine led to intrauterine growth retardation and intrauterine growth abnormalities including anancephaly, neonatal death and low birth weight. However, the teratogenic effects of nicotine have not previously been observed on skin. OBJECTIVE: We performed a study in order to observe histologically the teratogenic effects of nicotine on rat skin. MATERIALS & METHODS: Ten female Wistar-albino rats were separated into two groups, a control and an experimental group (n = 5). After the first week of pregnancy, the experimental group of rats were given nicotine intraperitoneally in a dosage of 2 mg/kg for two weeks. RESULTS: Striking teratogenic effects were observed in the experimental group of neonatal rats. Increased mitotic activity was noticed in the basal cells and hypertrophic epithelial cells were prominent in the epidermis. Chronic inflammatory cell infiltrate, fibrosis and extravasation of the erythrocytes were found in the dermis and hair follicles. CONCLUSION: Considerable teratogenic effects of nicotine were observed histologically on newborn rat skin. PMID- 11214965 TI - The effect of abdominal surgery on serum CA-125 levels. PMID- 11214966 TI - The size and sequence organization of the centromeric region of arabidopsis thaliana chromosome 5. AB - We have determined the size of the centromeric region of Arabidopsis thaliana chromosome 5, which corresponds to the genetically defined centromere by Copenhaver et al. (Science, 286, 2468-2474, 1999) on the basis of restriction analysis. As a large clone gap was present in the previously constructed contig map of the centromeric region, the restriction map of this region was constructed using Asc I, Not I, Apa I and Pme I and genomic DNA from a hypomethylated strain. The size of the centromeric region finally estimated by combination with the sequence data of cloned regions at both sides was 4.35 megabases (Mb). This value is over 2 Mb longer than those estimated in our previous work and also by Copenhaver et al. Combing this centromeric region with the physical map previously constructed, the entire length of chromosome 5 becomes 31 Mb. Although the internal moiety of the centromeric region has not been sequenced yet because of extremely high repetition, the result of sequence analysis from both sides toward the inside strongly suggests that the centromeric region is composed of the central 2.9-Mb domain consisting of mainly 180-bp repeats and Athila retrotransposons and flanking regions containing various types of transposons. On the basis of these observations, a structural model for the centromeric region is discussed. PMID- 11214967 TI - Complete structure of the chloroplast genome of a legume, Lotus japonicus. AB - The nucleotide sequence of the entire chloroplast genome (150,519 bp) of a legume, Lotus japonicus, has been determined. The circular double-stranded DNA contains a pair of inverted repeats of 25,156 bp which are separated by a small and a large single copy region of 18,271 bp and 81,936 bp, respectively. A total of 84 predicted protein-coding genes including 7 genes duplicated in the inverted repeat regions, 4 ribosomal RNA genes and 37 tRNA genes (30 gene species) representing 20 amino acids species were assigned on the genome based on similarity to genes previously identified in other chloroplasts. All the predicted genes were conserved among dicot plants except that rpl22, a gene encoding chloroplast ribosomal protein CL22, was missing in L. japonicus. Inversion of a 51-kb segment spanning rbcL to rpsl6 (positions 5161-56,176) in the large single copy region was observed in the chloroplast genome of L. japonicus. The sequence data and gene information are available on our World Wide Web database at http://www.kazusa.or.jp/en/plant/database.html. PMID- 11214968 TI - Complete genome structure of the nitrogen-fixing symbiotic bacterium Mesorhizobium loti. AB - The complete nucleotide sequence of the genome of a symbiotic bacterium Mesorhizobium loti strain MAFF303099 was determined. The genome of M. loti consisted of a single chromosome (7,036,071 bp) and two plasmids, designated as pMLa (351,911 bp) and pMLb (208, 315 bp). The chromosome comprises 6752 potential protein-coding genes, two sets of rRNA genes and 50 tRNA genes representing 47 tRNA species. Fifty-four percent of the potential protein genes showed sequence similarity to genes of known function, 21% to hypothetical genes, and the remaining 25% had no apparent similarity to reported genes. A 611-kb DNA segment, a highly probable candidate of a symbiotic island, was identified, and 30 genes for nitrogen fixation and 24 genes for nodulation were assigned in this region. Codon usage analysis suggested that the symbiotic island as well as the plasmids originated and were transmitted from other genetic systems. The genomes of two plasmids, pMLa and pMLb, contained 320 and 209 potential protein-coding genes, respectively, for a variety of biological functions. These include genes for the ABC-transporter system, phosphate assimilation, two-component system, DNA replication and conjugation, but only one gene for nodulation was identified. PMID- 11214969 TI - Cloning and genomic organization of the mouse gene slc23a1 encoding a vitamin C transporter. AB - Vitamin C is known to exist in particularly high concentrations in brain tissue, and its free radical scavenging function is thought to represent a major antioxidative defense system. We have cloned, sequenced and analyzed the genomic structure of a mouse sodium-dependent vitamin C transporter gene, Slc23a1 (also known as Svct2). The mouse Slc23a1 cDNA is 6.4 kb long and was cloned directly from a mouse brain RNA preparation. Hybridization screening of a mouse genomic BAC library identified BAC 53L21 which contains at least the entire coding sequence of the mouse Slc23a1 gene. Determination of the exon-intron structure of the gene revealed 17 exons ranging from 58 bp to 4407 bp extending over 50 kb of the mouse genome, with the translation start codon located in exon 3. Its 1944 nucleotide open reading frame encodes a polypeptide of 647 aa, which is highly similar to rat and human orthologs. The mouse gene was assigned to chromosome 2qG2 by fluorescence in situ hybridization analysis. Expression of this gene was demonstrated in a wide range of tissues, with especially high levels in brain. Neurodegenerative diseases with an established role for oxidative stress in the cytoplasm may therefore be conditions of SLC23A1 dysfunction. Key words: gene structure; Vitamin C; transporter; oxidative stress PMID- 11214970 TI - Prediction of the coding sequences of unidentified human genes. XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. AB - As an extension of our human cDNA project for accumulating sequence information on the coding sequences of unidentified genes, we here present the entire sequences of 100 cDNA clones of unidentified genes, named KIAA1673-KIAA1772, from three sets of size-fractionated cDNA libraries derived from human adult whole brain, hippocampus, and fetal whole brain. The average sizes of the inserts and corresponding open reading frames of cDNA clones analyzed here were 4.9 kb and 2.7 kb (corresponding to 895 amino acid residues), respectively. By computer assisted analysis of the deduced amino acid sequences, 44 predicted gene products were classified into five functional categories of proteins relating to cell signaling/communication, nucleic acid management, cell structure/motility, protein management, and metabolism. Furthermore, the expression profiles of the genes were also studied in 10 human tissues, 8 brain regions, spinal cord, fetal brain and fetal liver by reverse-transcription-coupled polymerase chain reaction, the products of which were quantified by enzyme-linked immunosorbent assay. PMID- 11214971 TI - Characterization of long cDNA clones from human adult spleen. AB - As an extension of our analysis of long cDNAs, we here report the characterization of cDNA clones from human adult spleen. From 2000 cDNA clones randomly sampled from a size-fractionated human spleen cDNA library (average size 4.5 kb), 97 clones were selected for sequencing according to their ability to code for protein at the 5'-end sequences and the novelty of their end sequences. The sequence data of these clones demonstrated that 87 out of 97 cDNA clones were derived from independent human genes. The average sizes of the inserts and corresponding open reading frames of these 87 cDNAs reached 4.5 kb and 1.4 kb (corresponding to 468 amino acid residues), respectively. In addition to these sequence analyses in silico, the expression profiles of the genes were also studied in ten human adult tissues by reverse transcription-coupled polymerase chain reaction, products of which were quantified by enzyme-linked immunosorbent assay. The results indicated that spleen could be used as an additional source of human long cDNAs to complement the list of human genes. PMID- 11214972 TI - Embarking on rice functional genomics via cDNA microarray: use of 3' UTR probes for specific gene expression analysis. PMID- 11214973 TI - Gene list on a plant tumor-inducing plasmid, pti-SAKURA in Agrobacterium tumefaciens MAFF301001. PMID- 11214974 TI - Complete genome structure of the nitrogen-fixing symbiotic bacterium Mesorhizobium loti (supplement). PMID- 11214975 TI - Effects of monaural versus binaural stimulation on P300 scalp topography in elderly listeners. AB - The P300 event-related potential was recorded from groups of young and elderly listeners in response to monaural and binaural stimulation. An oddball stimulus paradigm was used to record responses from 19 scalp locations. When listening to binaural stimuli, the young group showed midline and central P300 amplitude maxima, whereas the elderly group exhibited maximal responses in the midline and parietal regions. With monaural stimulation, the young group's responses were similar to those obtained with binaural stimulation. The elderly group, however, showed evidence of a greater contralateral hemisphere response to monaural stimulation during the early part of the P300 response. These findings support the possibility that the P300 neural generators may change with age with respect to temporal onset characteristics or their orientation and strength. PMID- 11214976 TI - Clinical application of the SADL scale in private practice II: predictive validity of fitting variables. Satisfaction with Amplification in Daily Life. AB - Predictive validity of 44 independent variables and their interactions with Satisfaction with Amplification in Daily Life (SADL) scores was assessed. SADL scores were influenced by patient age, years of hearing aid experience, hours of use per day, perceived hearing difficulty, pure-tone average, hearing aid style, processor type, and manufacturer's invoice cost. The relative importance of these variables to SADL measures was complex and very small, but the variables and their squares and interactions improved r2 predictions of SADL Global and subscale scores in a separate stepwise multiple linear regression procedure by 12 to 33 percent compared to SADL norms alone. More research with additional variables is needed to develop a clinically useful model for predicting wearer satisfaction. Clinically, SADL scores yield subscale-specific patterns of satisfaction and dissatisfaction that help in intervention planning and serve as graphic "snapshots" of satisfaction status. A series of patient profiles are presented illustrating the potential usefulness of the SADL in predicting hearing aid satisfaction. With its good construct and psychometric properties, the SADL could serve as a gold standard for satisfaction outcomes and a basis for development of a predictive model of hearing aid fitting success. PMID- 11214977 TI - NAL-NL1 procedure for fitting nonlinear hearing aids: characteristics and comparisons with other procedures. AB - A new procedure for fitting nonlinear hearing aids (National Acoustic Laboratories' nonlinear fitting procedure, version 1 [NAL-NL1]) is described. The rationale is to maximize speech intelligibility while constraining loudness to be normal or less. Speech intelligibility is predicted by the Speech Intelligibility Index (SII), which has been modified to account for the reduction in performance associated with increasing degrees of hearing loss, especially at high frequencies. Prescriptions are compared for the NAL-NL1, desired sensation level [input/output], FIG6, and a threshold version of the Independent Hearing Aid Fitting Forum procedures. For an average speech input level, the NAL-NL1 prescriptions are very similar to those of the well-established NAL-Revised, Profound procedure. Compared with the other procedures, NAL-NL1 prescribes less low-frequency gain for flat and upward sloping audiograms. It prescribes less high-frequency gain for steeply sloping high-frequency hearing losses. NAL-NL1 tends to prescribe less compression than the other procedures. All procedures differ considerably from one another for some audiograms. PMID- 11214978 TI - Effects of exercise and noise on auditory thresholds and distortion-product otoacoustic emissions. AB - Differences in auditory thresholds and distortion-product otoacoustic emission (DPOAE) levels were investigated as a function of gender, ear, frequency, and experimental condition: quiet sedentary activity, exercise, noise, and exercise and noise combined. In general, participants displayed significant elevations in auditory thresholds of approximately 6 to 13 dB following the two conditions employing noise exposure. There were no significant differences in either auditory threshold differences before and following the quiet and exercise conditions or between the noise-alone and combined exercise and noise conditions. Participants also displayed significant reductions in DPOAE levels of approximately 6 to 7 dB following the two conditions employing noise exposure. The findings also showed no gender or ear effects on auditory threshold or DPOAE level differences. Further, there was no evidence of a synergistic combination of exercise and noise on auditory function as revealed by changes in hearing threshold or DPOAE levels. PMID- 11214979 TI - Relation between slopes of word recognition psychometric functions and homogeneity of the stimulus materials. AB - This tutorial paper examines the relation between the slope of a mean word recognition function and the homogeneity or variability (with respect to recognition) of the individual stimulus items that compose the test materials. This was studied in terms of both the location (Cartesian) and slope of the psychometric functions of the individual words that compose the materials. Word recognition performances were measured for 100 CID W-22 (Hirsh) words and 100 PB 50 (Rush Hughes) words in quiet (0 to 56 dB HL in 8-dB steps) on 12 subjects with normal hearing. The functions for the individual W-22 words were more homogeneous (less variable) than were the functions for the individual PB-50 words. The mean function for the W-22 words was steeper (3.1%/dB) than the function for the PB-50 words (1.9%/dB). This evaluation of the individual words demonstrates the direct relation between variability of the test items and the slope of the mean psychometric function. The more homogeneous performance is on the individual test items with respect to both location and slope, the steeper the slope of the mean psychometric function. PMID- 11214980 TI - Diagnosis and management of foodborne illnesses: a primer for physicians. AB - This primer is directed to primary care physicians, who are more likely to see the index case of a potential food-related disease outbreak. It is a teaching tool to update primary care physicians about foodborne illness and remind them of their important role in recognizing suspicious symptoms, disease clusters, and etiologic agents, and reporting cases of foodborne illness to public health authorities. PMID- 11214982 TI - Program budgeting and marginal analysis: a priority-setting framework for Canadian Regional Health Authorities. AB - Health regions in Canada are responsible for meeting the needs of local populations with limited resources. However, relatively little attention has been given to this within-region resource allocation problem. An economic approach to needs assessment, namely program budgeting and marginal analysis, may be of benefit. Its potential for use in Canada is examined, in particular with examples from two Alberta health regions, the Calgary Regional Health Authority and the Chinook Health Region. PMID- 11214981 TI - Organizational justice principles and large-scale change: the case of program management. AB - Many of the barriers to implementation of large-scale change in healthcare organizations seem to be related to a lack of attention to the human change that needs to occur. One element of this human dimension that change agents overlook is the role that perception of fairness to employees plays in implementing large scale organizational change. This article uses program management (an organizational design that has been implemented in many healthcare facilities across Canada) as an example of large-scale structural change and demonstrates the importance of applying procedural and interactional justice principles to enhance the implementation of organizational change. PMID- 11214983 TI - The electronic health record: a destination or a journey? PMID- 11214984 TI - Differentiating among research, evaluation and measures to assure quality. AB - This article explores the similarities, differences and overlaps among research, evaluation and quality measurement. Criteria for determining the differences are offered as a quick guide to differentiating among them. These criteria are the purpose of the project, generalizability, intended use of the findings, intended subjects and intent to prove causation. Determining the key differences among research, evaluation and quality measurement facilitates the choice of restrictions, supports and reporting process that should be applied to each. PMID- 11214985 TI - Initiating regional quality management. AB - In June 1999, the Eastern Regional Health Board began to structure a regional quality management program that included quality, satisfaction and risk management initiatives. A regional plan for our two programs (Addiction Services and Public Health) and nine acute care facilities was needed. All had internal quality programs in place, at varying levels of maturity. Synthesis into a regional quality management plan was required. This article describes how one region planned and implemented this task over 10 months. Suggestions are included relating to required resources, a workable timeline and a communication strategy. PMID- 11214987 TI - Changing ourselves to help change our teams and organizations. Interview by Matthew D. Pavelich. PMID- 11214986 TI - Going beyond triage in Tajikistan. Health reform in the former Soviet Union. AB - Tajikistan is among the few countries where life expectancy diminished during the 1990's. To rebuild a health system fractured by economic collapse, political disintegration and civil war, the Essential Hospital Services Project was initiated to restore essential hospital services, encourage structural reform and build the health system's capacity to sustain itself. The article provides an overview of these reform efforts, outlines some of the challenges of health reform in Tajikistan and illustrates the benefits global partnerships can achieve when sharing creative new approaches to health reform. PMID- 11214988 TI - Hospitals taking second look at systems for thwarting infant kidnapping. PMID- 11214989 TI - Security and risk management coordination at a large medical center. PMID- 11214990 TI - Surveys: income of healthcare security directors continues to rise. PMID- 11214991 TI - Johnny Melles on replacing an older CCTV system with modern surveillance. PMID- 11214992 TI - How two major health systems are employing 'doing more with less' and 'value added' approaches to hospital security. AB - In efforts to achieve greater productivity from their security departments in the face of cutbacks, mergers, and other economic developments, a number of buzzwords have become popular recently that, in effect, call on security personnel to effectively provide additional services without increased funding or, in fact, with reduced budgets. Talking about such approaches is one thing, but achieving desired results is another. In this report, we'll present details on how security directors of two of the county's largest health operations have put concept into action. PMID- 11214993 TI - Dealing with census spikes at a state psychiatric facility. PMID- 11214994 TI - Ziegler: factors to be aware of in meeting JCAHO EOC requirements. PMID- 11214995 TI - Taking management of sickle cell disease to a new level. PMID- 11214996 TI - Patient, provider education targeted in efforts to curb antibiotic resistance. AB - Curb the overuse and misuse of antibiotics during the cough and cold season. Overuse is feeding the growing problem of antibiotic resistance. The result is billions spent to find new drugs and new cures for bugs that used to respond to front-line agents. Experts suggest the best way to address the problem is through patient and provider education. See how some regional efforts are faring, and take steps to address the problem in your organization. PMID- 11214997 TI - Patient empowerment touted as next step toward better preventive care. AB - Boost quality and outcomes through patient empowerment. How? By making claims information available to health plan members as well as physicians. At least one organization is making it happen with the help of a Web-based communications strategy. PMID- 11214998 TI - New guideline: step up efforts to prevent and treat diabetic foot disorders. AB - Prevent and treat diabetic foot disorders before complications multiply. They're the most common reason for hospitalization among diabetic patients, and such problems are costing billions each year to treat. However, some simple preventive steps at the primary care level could go a long way toward preventing or alleviating the more serious complications of diabetic foot disorders. Check out these new guidelines and new strategies for dealing with this costly issue. PMID- 11214999 TI - [In vitro antibacterial activity of prulifloxacin, a new oral quinolone, and comparative susceptibility rate at clinical breakpoint MIC]. AB - In vitro drug sensitivity of clinically isolated bacteria against prulifloxacin (PUFX), which is a new quinolone, was investigated, and the antibacterial activity and susceptibility rate at clinical breakpoint were compared with those of norfloxacin, ofloxacin (OFLX), ciprofloxacin, tosufloxacin, fleroxacin, sparfloxacin and levofloxacin (LVFX). The following results were obtained. 1) PUFX showed a broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacteria. 2) MIC80 of PUFX was 0.25 and 1 microgram/ml, against methicillin susceptible Staphylococcus aureus and Streptococcus pneumoniae, respectively and below 0.125 microgram/ml against Gram-negative Enterobacteriaceae. MIC90 of PUFX against Pseudomonas aeruginosa, which has MIC not exceeding 4 micrograms/ml to OFLX, was 0.5 microgram/ml. 3) PUFX was judged as active against the bacteria under the criteria proposed presented by "the Sensitivity Determination Committee for Antibiotics, Japan Society of Chemotherapy: Break Point for Respiratory Infectious Diseases and Sepsis". It is suggested that the sensitivity of each bacterial species to PUFX was high. 4) From the correlation analysis of MIC, PUFX was shown to have two to eight times higher antibacterial acitivity than LVFX for Citrobacter freundii, Serratia marcescens and Pseudomonas aeruginosa. 5) PUFX showed potent short-time bactericidal activity against S. aureus and P. aeruginosa. PMID- 11215000 TI - [Concentration of isepamicin sulfate in bone marrow blood]. AB - Fifteen patients who were performed a rotator cuff repair were subjected for the determination of a concentration of isepamicin sulfate (ISP), which was infused intravenously, in venous blood and bone marrow blood. The concentrations were measured at 0, 30, 60 minutes after the injection. There was no statistically significance between ISP concentrations in venous and bone marrow blood. This study revealed that the transference of ISP to the bone marrow was excellent. PMID- 11215001 TI - Journal transition points to a bright future for its contribution to public health. PMID- 11215002 TI - Diabetes in Victoria, Australia: the Visual Impairment Project. AB - OBJECTIVES: To establish the prevalence and characteristics of self-reported diabetes in a representative sample of Victorian residents aged 40 years and older, and to compare the vision between people with and without self-reported diabetes. DESIGN: Cross-sectional survey. SETTING: Nine randomly selected suburban Melbourne clusters and four randomly selected rural Victorian clusters. PARTICIPANTS: 4,744 subjects (86% participation rate) aged > or = 40 years. MAIN OUTCOME MEASURES: Subjects answered a detailed questionnaire which provided demographic details, body mass index, and the duration and treatment of any diagnosis of diabetes. Refraction was performed and best-corrected visual acuity was measured. RESULTS: The prevalence of self-reported diabetes was 5.1%. In a multivariate analysis, self-reported diabetes was positively associated with age (p < 0.01), male sex (p = 0.01), higher body mass index (p = 0.01), Mediterranean ethnicity (p = 0.01), unemployment (p = 0.05) and lack of private health insurance (p < 0.05). People with self-reported diabetes were more likely to have mild or moderate levels of visual impairment than people who reported no previous diagnosis of diabetes (p < 0.01). CONCLUSIONS: Diabetes in Victoria is more prevalent among men and among people of Mediterranean origin. When planning educational programs and health service delivery, it is also important to consider that, compared with the general population, people with diabetes are less likely to be employed or to have private health insurance, and are more likely to have impaired vision. PMID- 11215003 TI - Body mass index in aboriginal Australians in remote communities. AB - OBJECTIVES: To describe the distribution of body mass index (BMI) and estimate the prevalence of potential chronic energy deficiency (CED) and obesity in Aborigines in remote communities (ARC) in the Top End of the Northern Territory, Australia. METHODS: Centile charts were constructed for BMI from 1,631 sets of measurements from 1,138 Aborigines, aged five to 77 years, in three remote communities on the Tiwi Islands, using Cole's LMS method. These were compared with European, American white and American black reference charts. The prevalences of CED and obesity were also compared to the corresponding values from a national Indigenous sample. RESULTS: The BMI centiles change with age. Compared with reference populations, BMIs are lower in ARC children and adult males. Young adult females have similar BMIs to American black and higher BMIs than American white and French counterparts up to 45 years. Aborigines older than 50 years are 'thinner'. Compared with a national sample of Indigenous Australians, our sample has a higher prevalence of CED and a lower prevalence of obesity. CONCLUSIONS: The BMI centile curves describe the contemporary nutritional status in the remote communities. Nutritional status measured by BMI is different in ARC than in other populations. IMPLICATIONS: The difference in nutritional status between ARC and other populations should be considered when planning nutritional intervention strategies. The centile charts will allow health workers to determine the relative ranking of BMI for individual Aborigines in the remote communities. PMID- 11215004 TI - The Anti Cancer Council of Victoria FFQ: relative validity of nutrient intakes compared with weighed food records in young to middle-aged women in a study of iron supplementation. AB - OBJECTIVE: To assess the validity of the Anti Cancer Council of Victoria food frequency questionnaire (ACCVFFQ) relative to seven-day weighed food records (WFRs) in 63 women of child-bearing age. METHOD: 63 women completed WFRs to assess iron intake as part of a study on iron deficiency. These women also completed the ACCVFFQ. Nutrient intakes were computed independently for the WFRs and FFQs. Intakes were compared as group means, by correlation and by quintile classification, adjusting for day-to-day variation in intakes, and for energy intake. Individual differences in results were also examined. RESULTS: The strongest associations between WFR and FFQ results were energy-adjusted, log transformed and adjusted for day-to-day variability in intake. Correlation coefficients ranged from 0.28 for vitamin A to 0.78 for carbohydrate. Mean intakes from the WFRs and FFQs were within +/- 20% for 21 of 27 nutrients. Poor agreement between FFQs and WFRs for retinol intake was due to the inclusion of liver in two WFRs, an item which is not included in the FFQ. CONCLUSION: The ACCVFFQ performs as well as other FFQs for which validation data are available. The relatively poor measurement of retinol is consistent with other data, and with the limited number of foods in which this nutrient is abundant. IMPLICATIONS: The availability of an optically scannable valid instrument for assessing dietary intake will facilitate epidemiological studies of diet and disease, an area of current research priority. PMID- 11215005 TI - Neural tube defects in Victoria, Australia: potential contributing factors and public health implications. AB - OBJECTIVES: To measure population prevalence and determine potential predictors of neural tube defects. METHOD: Analysis of all births reported to a mandated collection of perinatal data, and terminations prior to 20 weeks' gestation that have been reported to a data collection of birth defects in Victoria from 1983 to 1997. Prevalence at birth and risk ratios of infant and maternal characteristics associated with neural tube defects were calculated. RESULTS: Prevalence of spina bifida has remained steady for 15 years and was 8.8/10,000 in 1997. Anencephaly increased to 7.9/10,000 in 1997. After exclusion of pregnancy terminations, the 1997 birth prevalence was 4.5/10,000 for spina bifida and 2.4/10,000 for anencephaly. Neural tube defects are identified in 1 in 1600 fetuses, the risk being significantly higher for epileptic women (Adjusted Odds Ratio (AOR) = 3.70, 95% CI 2.25-6.07), multiple births (AOR = 4.56, 95% CI 3.46-6.02), teenage mothers (AOR = 1.47, 95% CI 1.09-2.00) compared with those aged 25-29, and women with three or more previous pregnancies (AOR = 1.40, 95% CI 1.10-1.78). The risk was lower for women of East Asian (AOR = 0.70, 95% CI 0.49-1.00) and Middle Eastern origin (AOR = 0.60, 95% CI 0.35-1.02) and these differences were approaching statistical significance. CONCLUSION: Total prevalence of neural tube defects did not decline up to 1997. IMPLICATIONS: It is unlikely that targeting 'at risk' groups identified in this study would make a difference to neural tube defect incidence. However, consideration could be given to identifying larger 'at risk' groups such as those with homocysteine metabolism defects. PMID- 11215006 TI - What do women feel about community-based antenatal care? AB - OBJECTIVE: This study evaluated women's perceptions of a new community-based model of continuity of antenatal care, the St George Outreach Maternity Project (STOMP). The model was established in an attempt to address some of the ongoing concerns and criticisms regarding antenatal care in Australia: lack of continuity of care and caregiver; prolonged waiting times; and inaccessible clinics. METHODS: A randomised controlled trial was conducted with 1,089 women (550 in the experimental group and 539 in the control group). The experimental group (the STOMP group) received antenatal care from small teams of midwives and an obstetrician in community-based settings. Data were collected using a questionnaire administered at 36 weeks' gestation, with a response rate of 75%. RESULTS: Women in the STOMP group reported waiting significantly less time for antenatal visits with easier access to care. STOMP group women also reported a higher perceived 'quality' of antenatal care compared with the control group. STOMP group women saw slightly more midwives and fewer doctors than control group women did. CONCLUSION AND IMPLICATIONS: This model of care has implications for the planning and provision of antenatal services within the Australian public health system, which is increasingly moving towards a community-based emphasis. Antenatal care is a service that can be successfully transferred into community based settings with benefits for women. PMID- 11215007 TI - Cannabis use among Australian adolescents: findings of the 1998 National Drug Strategy Household Survey. AB - OBJECTIVE: To describe the prevalence, context and recent trends in cannabis use among Australian adolescents. METHOD: Data was collected from 1,581 adolescents aged 14-19 years as part of the 1998 National Drug Strategy Household Survey, and comparisons were made with data from 350 adolescents who participated in the 1995 survey. RESULTS: Among 14-19 year olds, 47.8% have had the opportunity to use cannabis in the past year and 45.2% have used cannabis at least once in their lifetime. Substantial increases have occurred since 1995 in the prevalence of use among young females. While most cannabis use was fairly infrequent, a minority of 14-19 year olds (9.4%) used cannabis at least weekly. Cannabis use was associated with regular tobacco and alcohol use, and other illicit drug use. Regular cannabis users had lower levels of health on the general health and vitality dimensions of the SF-36. IMPLICATIONS: These results show that cannabis availability and use is common among Australian adolescents, and confirm that there has been an increase in use between 1995 and 1998, although only among young females. Future research is required to understand why this recent increase has occurred, and trends in cannabis uptake and use patterns among this group should be carefully monitored. Interventions may need to be developed and made available to the group of young people who are using cannabis heavily. PMID- 11215008 TI - Impact of increasing the re-supply interval on the seasonality of subsidised prescription use in Australia. AB - OBJECTIVE: To evaluate the impact of increasing the minimum re-supply period for prescriptions on the Pharmaceutical Benefits Scheme (PBS) in November 1994. The intervention was designed to reduce the stockpiling of medicines used for chronic medical conditions under the PBS safety net. METHODS: Interrupted times series regression analyses were performed on 114 months of PBS drug utilisation data from January 1991 to June 2000. These analyses assessed whether there had been a significant interaction between the onset of the intervention in November 1994 and the extreme levels of drug utilisation in the months of December (peak utilisation) and January (lowest utilisation) respectively. Both serial and 12 month lag autocorrelations were controlled for. RESULTS: The onset of the intervention was associated with a significant reduction in the December peak in drug utilisation; after the introduction of the policy there were 1,150,196 fewer prescriptions on average for that month (95% CI 708,333-1,592,059). There was, however, no significant change in the low level of utilisation in January. The effect of the policy appears to be decreasing across successive post-intervention years, though the odds of a prescription being dispensed in December remained significantly lower in 1999 compared to each of the pre-intervention years (11% vs. 14%). CONCLUSION: Analysis of the impact of increasing the re-supply period for PBS prescriptions showed that the magnitude of peak utilisation in December had been markedly reduced by the policy, though this effect appears to be decreasing over time. Continued monitoring and policy review is warranted in order to ensure that the initial effect of the intervention be maintained. PMID- 11215009 TI - Dying to go on holiday. AB - OBJECTIVE: The Christmas period road toll is a highly publicized 'summary' of the number of road deaths that occur each year during New Zealand's summer holiday period. Our aims were to identify significant changes in the Christmas road toll during 1968-98, highlight the ability to detect changes and determine if focusing on the changes in the Christmas road toll provided a useful insight into trends in fatal crashes. METHODS: Regression modelling of the number of fatalities was used to examine trends in the Christmas road toll in New Zealand over time. A power analysis was used to investigate the ability to detect significant reductions in the Christmas road toll. RESULTS: The Christmas road toll has not decreased significantly in the past 30 years and has not improved significantly in contrast to the rest of the year. The number of deaths in any given year can be expected to vary 'naturally' between 10 and 39. The statistical power to detect a hypothetical 19% reduction in the Christmas road toll is minimal. CONCLUSIONS: Stochastic fluctuations in the Christmas road toll make it extremely difficult to identify underlying trends, even if substantial. Little insight can be gained from yearly comparisons of road tolls considered over short periods. More focus should be placed on road tolls that are calculated over longer periods, e.g. the previous six months. IMPLICATIONS: Natural fluctuations arising in small counts will make it difficult to highlight real improvements in road tolls. PMID- 11215010 TI - Socio-demographic correlates of screening intention for colorectal cancer. AB - OBJECTIVE: To assess the relationship between socio-demographic factors and screening intention for colorectal cancer (CRC). METHODS: A cross-sectional survey of a random sample of 884 Queenslanders aged 40-80 years was conducted using a computer-assisted telephone interviewing system. The factors measured included socio-demographic characteristics, personal history of CRC, knowledge of others with CRC and perceived symptom status. Chi-squared and Monte Carlo estimates of Fisher Exact Tests were performed to determine the associations between socio-demographic factors and screening intention. In multivariate analyses, multinomial logistic regression (MNLR) was utilised to examine potential determinants of screening intention. RESULTS: 77.5% (95% CI 74.0% 80.7%) of the respondents indicated their intention to participate in CRC screening if it were recommended by their doctor or health authorities. The likelihood ratio chi-squared tests in the MNLR analyses show that age (chi(df = 6)2 = 15.0; p = 0.02), education (chi(df = 8)2 = 19.4; p = 0.01), perceived symptom status (chi(df = 4)2 = 22.9; p = 0.00), sex (chi(df = 2)2 = 4.5; p = 0.11), income (chi(df = 14)2 = 19.6; p = 0.14) and personal history of CRC (chi(df = 2)2 = 4.3; p = 0.12) were potential determinants of screening intention. Other socio-demographic factors, including country of birth, private health insurance status, Socio-economic Index for Areas, and Rural and Remote Areas Classification codes, were not associated with screening intention. CONCLUSIONS AND IMPLICATIONS: The results indicate that a variety of socio demographic factors are associated with screening intention and need to be considered in the future development of a population-based screening program for CRC. PMID- 11215012 TI - How well does a telephone questionnaire measure drinking water intake? AB - BACKGROUND: Few studies have assessed the validity or reliability of drinking water intake estimations. In studies investigating potential waterborne disease, this is very important. METHODS: We carried out a validity and reliability study to evaluate water intake estimations. The validity part of the study compared a telephone questionnaire to a diary. The reliability part of the study compared two telephone questionnaires. RESULTS: 253 participants were recruited. The most commonly consumed water intake categories were plain and boiled tap water. For persons aged less than 12 years, the median volume of plain water consumption was 2.9 glasses/day according to the diary. For persons aged 12 years and over, the median volume of plain water consumption was 3.0 glasses/day and for boiled water 3.0 glasses/day according to the diary. There was negligible systematic over or under reporting by participants for the telephone questionnaire in comparison to the diary and for the comparison of both telephone questionnaires. Water intake estimates were converted to categorical variables and the per cent agreement and weighted kappa statistics were calculated. For both the validity and reliability parts of the study the per cent agreement was 57-78% and the weighted kappa was 0.57-0.81. CONCLUSION: Water intake estimates show only moderate levels of validity and reliability when using a telephone questionnaire in comparison to a diary. IMPLICATIONS: Investigators of potential waterborne disease or nutritional research should exercise some caution in drawing conclusions from minor differences in drinking water intake that are obtained from a telephone questionnaire. PMID- 11215011 TI - Participation of older males in a study on photography as an aid to early detection of melanoma. AB - OBJECTIVE: To examine the acceptability of photography as an aid to skin examinations in men over 50 years of age. METHODS: A randomised trial of men selected from the electoral roll. All participants were photographed, but only half received their photographs. Skin examinations by GPs at years one and two. RESULTS: 55% of men consented to have photographs taken and 51% did so. 86% of respondents had risk factors for melanoma (compared to 68% of non-responders) and 47% had two or more risk factors (compared to 23% of non-responders). At year one, 91% of participants remaining in study regions had been examined. Photographs were lost by only six participants. CONCLUSIONS: Men over 50 years of age respond to personalised health messages about melanoma and respondents include a high proportion of males with risk factors for melanoma. IMPLICATIONS: These initial results suggest that photography may be a logistically acceptable approach for assisting in the early detection of melanoma. PMID- 11215013 TI - Aspects of tooth decay in recently arrived refugees. AB - OBJECTIVE: To measure and compare the prevalence and distribution of tooth decay among two refugee groups recently arrived in Australia. METHOD: The study included refugees aged 15-44 years from Iraq and the former Yugoslavia and random, age-matched social security recipients attending for emergency dental care in 1996. RESULTS: In younger persons, former Yugoslavian refugees had significantly greater decay experience than Iraqis and emergency care recipients. Refugees had significantly more untreated decay than emergency care recipients and a similar distribution of untreated decayed teeth, with only 15% having none and more than 10% having high decay levels. More than 33% of emergency care recipients had no untreated decay and less than 5% had high levels. CONCLUSION: Significant differences were found between refugees and emergency dental care recipients, with refugees having a higher prevalence and more uniform distribution of untreated decay. IMPLICATIONS: Consistent with public health objectives, the finding that refugees had significantly more untreated decay than other disadvantaged Australians provides support for improved access to dental care during the settlement period. PMID- 11215014 TI - The establishment of an industry-based education program in public health. AB - Commonwealth reforms have led to staff of the Department of Health and Aged Care needing a greater knowledge of public health, to more effectively evaluate evidence and to quickly acquire competence in new emerging areas. The department's requirements of a training program could not be met by existing university-based public health courses. A consortium of five universities and the department worked together to develop an industry-based course that would meet the Commonwealth's needs. The course was constituted within university regulations; had an incremental and articulated structure with exit points at certificate, diploma and Masters levels; was relevant to the work of staff; offered subjects which complemented the staff's existing skills, training and career aspirations; drew upon expertise across the universities; and was flexible in its delivery. The Commonwealth's and universities' experience has been sufficiently positive to conclude that a corporate public health postgraduate program has a place alongside university-based programs. PMID- 11215015 TI - Impacts of climate and climate change on medications and human health. AB - OBJECTIVE: To examine impacts of climate and climate change on medications and human health. METHODS: Literature review and analysis of MIMS. RESULTS: Changed climate associated with the enhanced Greenhouse Effect (e.g. increased temperature) may lead to medication-related health impacts through deterioration of storage conditions, increased heat stress from medication-induced heat intolerance, and by influencing pharmacokinetics. Increases in UV radiation from stratospheric ozone depletion may increase the significance of medications that can lead to an increased sensitivity to the damaging effects of UV radiation (i.e. photosensitivity). CONCLUSIONS AND IMPLICATIONS: Raising awareness of the impacts of climate on medications, and of climate-related side-effects, among both health care professionals and the public, should modify behaviour and therefore reduce the risks of such adverse impacts. PMID- 11215016 TI - Accidents in older people living at home: a community-based study assessing prevalence, type, location and injuries. AB - OBJECTIVES: To assess the prevalence, type, location of and injuries from home accidents, including falls and other accidents, and to explore whether variables including socio-demographic characteristics, medication use and home hazards were associated with all home accidents and falls. METHOD: 657 older people were interviewed about accidents in the previous four weeks. For a subsample (n = 425), a home hazard check was completed. RESULTS: Of the 101 accidents reported, 51% (n = 51) were falls and 50% (n = 50) were other accidents. The most common location for all accidents was outside (30%). Most resulted in minor injury to the legs (43%) or arms (39%). Medical treatment was sought for 14% of accidents. Having more than five hazards and infrequent home visits by healthcare providers were associated with having at least one accident and at least one fall. Use of a walking aid was also associated with falling. CONCLUSION: Rates of falls and other accidents are considerable. IMPLICATIONS: Work is required to confirm the importance of the relationships suggested and to provide data on the burden of injury associated with non-fall accidents. PMID- 11215017 TI - Cannabis: a Trojan horse for nicotine? PMID- 11215018 TI - Re: 'Birthweights and growth of infants in five aboriginal communities'. PMID- 11215019 TI - Just who is 'wrong' about the implications of heroin trials? PMID- 11215020 TI - Overwhelming support for smoking bans. PMID- 11215021 TI - The prevalence, incidence and distribution of human urinary schistosomiasis in Edo State, Nigeria. PMID- 11215022 TI - Digital architect . Self-service design. PMID- 11215024 TI - Surgeon General focuses on children with mental illnesses. PMID- 11215023 TI - Soothing the pain of soaring power prices. PMID- 11215025 TI - Dangers of psychoactive medication use in the elderly. PMID- 11215026 TI - Potential alternative to electroconvulsive therapy: pacemaker for the brain. PMID- 11215027 TI - Using structured writing experiences to promote mental health. AB - 1. Structured writing activities can be used in a therapeutic context for diverse purposes. 2. Selecting a particular writing modality should be based on individual clients' needs and abilities. 3. Therapeutic goals for writing interventions should be defined clearly prior to implementation. PMID- 11215028 TI - Dysphagia in psychiatric patients. AB - 1. Psychiatric patients in acute and long-term care settings may be at high risk for dysphagia and its sequelae. 2. The prevalence of dysphagia in the psychiatric population is higher than commonly believed. 3. Routine screening is essential for the safety and management of psychiatric patients at risk for dysphagia. PMID- 11215029 TI - Philosophical basis and practice of self-awareness in psychiatric nursing. AB - 1. Reflection on one's reasoning and judgments to become cognizant of what is in the unconscious mind, not what should be there according to a belief system, theory, or teachings, is necessary for the development of self-awareness. 2. The process of self-awareness compels nurses to examine their own value positions so these biases and prejudices are not projected onto others, and so nurses do not reject others who do not share similar values. 3. Seeking answers to the questions generated through self-awareness can make interpersonal work with clients dynamic, living experiences, which can bring a sense of satisfaction and meaning to nurses' work. PMID- 11215030 TI - Japanese expert public health nurses empower clients with schizophrenia living in the community. AB - 1. Home visiting psychiatric public health nurses are integral to expanding community-based mental health services for Japanese citizens living with schizophrenia and other mental illnesses. 2. Interviews with experienced psychiatric public health nurses revealed empowerment as the basic social process that guides their practice. Five empowering practice domains foster client autonomy. 3. Psychiatric public health nurses work with families, neighbors, educators, and employers to enable their clients' healthy living in the community. PMID- 11215032 TI - The definition of the situation is the situation. PMID- 11215031 TI - Listening. PMID- 11215033 TI - New ruling more than a bonus. HHS' approval of limited gain-sharing arrangement may lead to national trend. PMID- 11215034 TI - 2001 Trustees of the Year. Beth Israel's ironman rescues hospital from fiscal implosion. PMID- 11215035 TI - 2001 Trustees of the Year. Chairman's negotiating skills bring success to rural hospital. PMID- 11215036 TI - Patient-safety evangelism. Allina CEO Sprenger preaches importance of executive involvement. PMID- 11215037 TI - Blessed with a healthy bottom line. Bon Secours has avoided losses despite BBA, other operational challenges. PMID- 11215038 TI - For-profits take root in Pa. Many hospitals need cash, and big chains have it. PMID- 11215039 TI - More revenue, at a cost. Hospitals' price hikes imperil additional federal Medicare, Medicaid relief. PMID- 11215040 TI - Quantification of porcine follicle-stimulating hormone receptor messenger ribonucleic acid by reverse transcription-competitive polymerase chain reaction. AB - An easy and reliable method was developed for construction and quantification of competitive templates, which shared the same sequence as the amplified target DNA except for a 20-bp insertion in the middle by recombinant polymerase chain reaction (PCR). Among the advantages of competitive PCR is that any predictable or unpredictable variable that affects amplification has the same effect on both target and competitor species and that the final ratio of amplified products reflects exactly the initial targets. The utilization of a thermostable reverse transcriptase in the RT step was proposed to overcome the problem of the efficiency of target cDNA synthesis. In addition, to obtain reliable measurements, it was recommended to perform four PCR with amounts of competitive template flanking the concentration of the target mRNA. PMID- 11215041 TI - Influence of single base change in Shine-Dalgarno sequence on the stability of B. subtilis plasmid PSM604. AB - B. Subtilis expression plasmids generally require a stringent Shine-Dalgarno Sequence (SDS). Site-directed-mutagenesis was explored to change the Shine Dalgarno Sequence from AAAAATGGGG (mutant type) to AAAAAGGGGG (wild type) in recombinant plasmid PSM604. The single base substitution made the plasmid with wild SDS unstable in structure and segregation. The interaction of SDS with subtilisin leader sequence of PSM604 might be responsible for the instability of plasmid. PMID- 11215042 TI - Construction and identification of recombinant adenovirus vector containing the hVEGF165 gene. AB - To construct the recombinant adenovirus vector containing the cDNA for human vascular endothelial growth factor (hVEGF165), the cDNA for hVEGF165 was subcloned into pACCMV.pLpA. Subsequently, this recombinant pACCMV.hVEGF was co transfected into 293 cells together with pJM17 to obtain the replication deficient recombinant adenovirus containing hVEGF gene--AdCMV.hVEGF. The VEGF gene expression was detected by using RT-PCR and Western blot in rabbit aorta vascular smooth muscle cells (VSMC) infected with AdCMV.hVEGF. Cultured human umbilical vein endothelial cells (HUVEC) were incubated with the conditioned medium (CM) from above mentioned VSMC infected with AdCMV.hVEGF to observe the effect of VEGF on proliferation of HUVEC. 48 h after the infection with AdCMV.hVEGF, VSMC demonstrated VEGF expression, and the expressed VEGF could stimulate the proliferation of HUVEC in vitro. Successfully prepared AdCMV.hVEGF165 could express biologically active VEGF in infected VSMC, and stimulate proliferation of HUVEC. PMID- 11215043 TI - Effect of polypeptide CH50 on macrophage activation in vivo and anti-tumor function. AB - The main features of CH50, a recombinant polypeptide of human fibronectin, activating macrophages in vivo and its anti-tumor function were investigated. After injection of CH50 and(or) transfection of IFN-gamma gene in vivo, several kinds of factors produced by macrophages were determined and the growth of tumor in vivo was measured. CH50 could enhance the production of such factors as NO, TNF and IL-1 by macrophages, but the activation of macrophages was relatively slow when CH50 was used in vivo alone. CH50 and IFN-gamma could synergistically activate macrophages rapidly in vivo no matter whether the injection of CH50 or the transfection of IFN-gamma gene was performed first. Injection of CH50 alone inhibited the formation of tumor nodes in a dose-dependent manner. Low dose of CH50 could strongly inhibit the formation of tumor nodes less than 1 mm, while high dose of CH50 could inhibit those more than 1 mm. A stronger inhibition on the growth of tumor in vivo was obtained by the synergistic effect of CH50 and IFN-gamma. CH50 and IFN-gamma, as double-signal factors for activation of macrophages, will be potentially useful in tumortherapy. PMID- 11215044 TI - Effect of c-myc antisense oligodeoxynucleotides on hypoxia-induced proliferation of pulmonary vascular pericytes. AB - To study the effect of c-myc antisense oligodeoxynucleotides (ODNs) on proliferation of pulmonary vascular pericytes (PC) induced by hypoxia, cell culture, dot hybridization using probe of digoxigenin-11-dUTP-labeled cDNA, 3H thymidine incorporation, immunocytochemical technique and image analysis methods were used to observe the effect of c-myc antisense ODNs on expression of c-myc gene and proliferating cell nuclear antigen (PCNA), and 3H-thymidine incorporation of PC induced by hypoxia. The results showed that hypoxia could significantly enhance the expression of c-myc and PCNA (P < 0.01), and elevate 3H thymidine incorporation of PC (P < 0.01), but antisense ODNs could significantly inhibit the expression of c-myc and PCNA (P < 0.05), and 3H-thymidine incorporation of PC (P < 0.01). It was suggested that hypoxia could promote the proliferation of PC by up-regulating the expression of c-myc gene, but c-myc antisense ODNs could inhibit hypoxia-induced proliferation of PC by downregulating the expression of c-myc gene. PMID- 11215045 TI - Effects of prostaglandins and leukotrienes on hypoxic pulmonary vasoconstriction in rats. AB - To investigate the effects of prostaglandins (PGs) and leukotrienes (LTs) on hypoxic pulmonary vasoconstriction (HPV), in vivo rats experiment and in vitro perfused lung experiment were conducted. The effect of hypoxia on hemodynamics, concentrations of TXB2 and 6-keto-PGF1 alpha in serum and lung tissue during hypoxia and effects of PGs and LTs on HPV were observed. The results showed that pulmonary arterial pressure (Ppa) and pulmonary vascular resistance were increased during hypoxia, but cardiac output and systemic arterial pressure were decreased. There were increases of the concentrations of TXB2 and 6-keto-PGF1 alpha and their ratio in serum and lung tissue during hypoxia. After use of cyclooxygenase inhibitor (indomethacin) in vivo and in vitro, HPV was augmented respectively, but after use of lipoxygenase inhibitor (diethylcorbamazine) or leukotriene receptor blocker (LY-171883), HPV was attenuated. It was suggested that LTs mediated pulmonary vasoconstriction, PGs inhibited pulmonary vasoconstriction and they played a modulating role during hypoxia. PMID- 11215046 TI - The change of interleukin-6 and tumor necrosis factor in patients with obstructive sleep apnea syndrome. AB - The levels of lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) expression in culture of peripheral blood mononuclear cells (PBMC) and the plasma levels of IL-6 and TNF-alpha in the patients with obstructive sleep apnea syndrome (OSAS) were measured and the relationship between OSAS and IL-6 or TNF-alpha expression studied. Both IL-6 and TNF-alpha were detected by using ELISA in 22 patients with OSAS and 16 normal controls. The levels of LPS-induced IL-6 (787.82 +/- 151.97 pg/ml) and TNF-alpha (4165.45 +/- 1501.43 pg/ml) expression in the supernatant of the culture of PBMC and plasma level of IL-6 (50.67 +/- 4.70 pg/ml) and TNF-alpha (299.09 +/- 43.57 pg/ml) in the patients with OSAS were significantly higher than those in the normal controls (in the supernatant of the culture of PBMC: 562.69 +/- 197.54 pg/ml and 1596.25 +/- 403.08 pg/ml respectively; in the plasma; 12.69 +/- 2.75 pg/ml and 101.88 +/- 21.27 pg/ml respectively). There were significantly positive correlation between the levels of IL-6 and TNF-alpha and the percentage of time of apnea and hyponea, as well as the percentage of time spending at SaO2 below 90% in the total sleep time. It was concluded that LPS-induced IL-6 and TNF-alpha levels as well as plasma IL-6 and TNF-alpha levels in the patients with OSAS were up-regulated, which may be associated with the pathogenesis of OSAS. PMID- 11215047 TI - Study on the correlation of plasma NO, ET-1 and ALT in the patients with chronic hepatitis and cirrhosis. AB - The levels of plasma nitric oxide (NO), endothelin-1 (ET-1) and ALT in the patients with chronic hepatitis B and active cirrhosis and the correlation among them were observed and analyzed. NO3- was restored by using cadmium column assay and NO2- measured by heavy nitrogen assay. The primitive NO3- and total restored NO2- (NO3-/NO2-) in plasma of the patients with chronic hepatitis and cirrhosis. Plasma ET-1 and ALT levels were determined by using radioimmunological assay and Lai's assay, respectively. Compared with normal control group, the plasma levels of NO2-/NO2- and ET-1 in the patients with chronic active hepatitis and active cirrhosis were significantly increased (P < 0.05-0.01). There was a positive correlation between NO and ALT, and ET-1 and ALT in the patients with chronic active hepatitis and active cirrhosis respectively. It was suggested that elevation of both NO and ET-1 levels were closely related with injury severity of liver function. PMID- 11215049 TI - Methodological study of cell separation with domestic immunomagnetic beads. AB - To establish the method of cell separation with domestic immuomagnetic beads, three methods were investigated. Direct method, SPA method and Biotin-Avidin method were applied to separate cell strain Hut-78 and CD4 positive cells. Separation rate of strain Hut-78 was more than 90% in direct method. Detachment rate with papain was over 95%. Cell activity was well retained. SPA method and Biotin-Avidin methods were also effective, but the direct method was superior to the other two techniques. Before separated by the direct method, CD4 positive cells constituted 46.4% +/- 6.4% of mononuclear cells (MNC), but in eliminated suspension there was only 6.2% +/- 2.3% CD4 positive cells left. In the separated part, 80.6% +/- 7.2% of the cells combined with the beads. It is concluded that the direct method in separating cells had high sensitivity and specificity. PMID- 11215048 TI - Experimental study on the effect of ligustrazine in the prevention of intimal proliferation of deendothelial artery. AB - To evaluate the possibility of employing ligustrazine in the prevention of restenosis, the effects of ligustrazine on the intimal thickening of air-injured carotid artery of rats were investigated, and the effects of ligustrazine on the proliferation of rabbit aortic median smooth muscle cells (SMCs) cultivated in vitro were examined. Artery injury model of 18 rats of about 3 months old was established by Fishman air-dry method. Fourteen days after operation, the maximal artery intimal and medial thickness of the control and ligustrazine group was measured on the image analysis system. Using cell counting and thymidine (3H-TdR) up-take method, we also examined the effects of ligustrazine on the proliferation of aortic median SMC from 4 rabbits. Ligustrazine was found to inhibit the proliferation and 3H-TdR up-take of SMC in a dose-dependent manner in vitro (P < 0.05 or P < 0.01 vs control). It also inhibited the intimal thickening of rat arteries after deendothelialization. The maximal intimal thickness of ligustrazine group was much thinner than that of the control (35.9 +/- 3.8 microns vs 80.2 +/- 23.4 microns, P < 0.01). It was showed that ligustrazine could be used for prevention of restenosis in clinical practice. PMID- 11215050 TI - Study on P16 gene in acute leukemia. AB - To study the change of suppressing cancer gene P16 in acute leukemia, the P16 antigen expression of leukemia cell surfaces in 61 cases were investigated with ABC assay and gene structural defects in 51 cases of acute leukemia were examined with multiple comparative PCR method. It was found that antigen expression of P16 in leukemia was obviously lower than that innormal subjects (P < 0.001). At the same time, antigen expression in All was lower than that AML (P < 0.05). No significant difference was found between the complete remission (CR) and non remission (NR) subjects from AML and ALL groups (P > 0.05). THe exon 2 of P16 gene showed homozygous deletion only inn 4 cases out of 30 cases in ALL. No structural defect was revealed in 21 cases of AML. It was suggested that expression defect of P16 gene was a main cause in development and progression of acute leukemia, and structural defect of exon 2 was not a primary molecular event. PMID- 11215051 TI - Clinical and biochemical characteristics of growth hormone-secreting pituitary tumors. AB - To investigate the difference of biochemical characteristics on gsp-positive and gsp-negative growth hormone (GH)-secreting pituitary tumors, 18 GH-secreting pituitary tumors were examined for their clinical characteristics and gsp oncogenes. All patients received the pituitary function combinative stimulating test. It was found that there were no difference in the sex, age, tumor size, course of disease and plasma basal GH levels with gsp-positive and gsp-negative patients. The plasma levels of PRL were increased in most patients (11/18), and the plasma levels of TSH in gsp-positive patients were higher than those in gsp negative patients (P < 0.05). There was no significant difference in the responses to pituitary combinative stimulating test in gsp-positive and gsp negative patients. It was concluded that there was little difference in the clinical biochemical characteristics of gsp-positive with gsp-negative GH secreting pituitary tumors. PMID- 11215052 TI - Preliminary study on the relationship between cAMP level and gsp expression in cultured human pituitary somatotrophinomas. AB - In order to investigate the relationship between abnormal intracellular signal transduction and tumorgenesis of human pituitary somatotrophinomas, the effects of protein kinase A (PKA)-dependent growth hormone (GH) releasing hormone (GHRH) and protein kinase C (PKC)-dependent GH-releasing peptide (GHRP-6) on cAMP production were observed by using cell culture and biochemical methods, and the expression of the gsp oncogene was detected by using PCR and direct sequence assay methods in 11 patients with human pituitary somatotrophinomas. It was found that GHRP-6 exerted significant stimulatory effect on cAMP production by 2 gsp positive tumors and no effect on the gsp-negative tumors. GHRP-6 could enhance the stimulation of cAMP production induced by GHRH in tumor without gsp oncogenes. It was suggested that both GHRH and GHRP-6 exert identical effects on human pituitary soamtotrophinomas, which was contributed to the cross-talk between the two intracellular signal transduction pathways in pituitary cells. PMID- 11215053 TI - The regulatory effects of protein kinase C on the proliferation of cultured human low-passage meningioma cells. AB - The potential role of the protein kinase C (PKC)-mediated signal transduction pathways in growth regulation was evaluated and the effects and the possible mechanism of PKC inhibitor on low-passage human meningioma cells in vitro investigated. Freshly resected meningiomas obtained from the operation were placed into cell cultures. Cells from early-passage were used for the following experiments. The numbers of the cultured meningioma cells were counted to evaluate the effect of the PKC inhibitor staurosporine on proliferation of meningioma cells. The basal phosphatidylinositol (PI) turnover rate and the inhibitory rate of starosporine on the proliferation of the meningioma cells were detected. It was found that the proliferation of the low-passage human meningioma cells was inhibited by staurosporine in a dose-dependent manner. The inhibitory rate of staurosporine was positively correlated with the basal PI turnover rate (r = 0.58, P < 0.01). It was suggested that PKC-mediated signal pathway is involved in the proliferation of the low-passage human meningioma cells. The procedure that PKC regulated the proliferation of human meningioma cells is a complex procedure. It is necessary to make more research in order to explore a non-operation therapy or an adjuvant therapy. PMID- 11215054 TI - Expression of p53 and p21 protein in transitional mucosa adjacent to rectal carcinoma and its clinical implication. AB - To study the biopathological characteristics of the transitional mucosa adjacent to rectal carcinoma, 34 cases were subjected to mucin histochemical and immunohistochemical study to observe the expression of p53 and p21 protein in distal mucosa adjacent to rectal carcinoma and its relationship to the mucin change. The expression of p53 protein was found in 29.4% (10/34) of distal transitional mucosa in the cytoplasm of goblet cells, and its positive staining was within 4 cm from carcinoma margin. All p53 positive mucosa was transitional mucosa. Overexpression of p21 protein was found in 26.5% (9/34) of distal transitional mucosa in cytoplasm of crypt cells, and its positive staining was within 2 cm from carcinoma margin. There was no relationship between the expression of p53 and p21 protein in carcinoma and that in transitional mucosa (P > 0.05). These findings indicated that there was aberrant alteration of p53 and p21 genes in transitional mucosa adjacent to colorectal carcinoma, which provided further evidence that transitional mucosa was an unstable pre-cancerous change. The aberrant mucin change and genetic alteration in distal mucosa of rectal cancer is within 4 cm. PMID- 11215055 TI - The relationship between apoptosis and the expression of proliferating cell nuclear antigen and the clinical stages in gastric carcinoma. AB - The relationship between the apoptosis and the expression of proliferating cell nuclear antigen (PCNA) and the clinical stages in gastric cancers was studied. By using terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) technique and PCNA immunohistochemical staining, the apoptosis and the expression of PCNA in tissue of gastric carcinoma were assayed in situ, the index of apoptosis (AI), index of PCNA (PI) and the rate of AI/PI were calculated. AI and PI in gastric cancer tissues were (6.5 +/- 3.7)% and (49.8 +/- 15.9)% respectively, and the rate of AI/PI was 0.13 +/- 0.05, which were obviously different from those of normal gastric mucosa in paragastric cancer (P < 0.01). With the advanced TNM stages of gastric carcinoma, the AI was decreased, PI was increased and the rate of AI/PI decreased in gastric carcinoma. There was significant difference in them between the gastric cancer tissues and normal gastric mucosa in pericarcinoma in TNM stage II to IV (P < 0.05). It was suggested that the decreased apoptotic cells and the increased proliferating cells were obviously related to the tumor genesis and tumor progression in gastric carcinoma. The AI, PI and the rate of AI/PI would become the prognostic factors in advanced gastric carcinoma. PMID- 11215056 TI - Variation of perioperative blood cTnT levels in patients undergoing cardiopulmonary bypass and its clinical implication. AB - The clinical value of cardiac Troponin T (cTnT) as a marker in assessing myocardial cell damage in the patients undergoing open heart surgery was studied. Serum cTnT and CK-MB levels were measured in serial blood samples from 20 patients undergoing open heart surgery before operation, at aorta clamping, aorta opening, the end of CPB and the operation, and subsequently one h, one day, 3 days and one week after operation respectively. Ten patients receiving thoracic surgery were also subjected to the measurement of cTnT and CK-MB before and 24 h after operation. The results showed that peak concentrations were reached earlier in cTnT than in CK-MB, and the circulation cTnT remained high when CK-MB had already decreased to normal. In 10 patients receiving thoracic surgery, cTnT level was normal and CK-MB was increased in 4 patients after surgery. It was concluded that the sensitivity and specificity of cTnT was more than those of CK MB and cTnT could be used as a routine indicator for myocardiac protection. PMID- 11215057 TI - Study on angiogenesis factor of human osteosarcoma. AB - Angiogenesis factor of human osteosarcoma was partially purified and its biological features were studied. The active peptide with 8000 to 10,000 u molecular weight in the conditioned medium obtained from the cultivation of human osteosarcoma cells were partially purified by ultrafiltration, chromatography and dialysis. The angiogenic effects of the fractions were assessed by proliferation assay of human umbilical vein and pig aorta thoracic endothelial cells. The results showed that the chromatography fractions of 4 to 6 could significantly promote the proliferation of the endothelial cells. It was suggested that the human osteosarcoma cells could synthesize and secrete angiogenesis factor with a molecular weight of 8000 to 10,000 u. PMID- 11215058 TI - The effect of different interventional treatment on P-Glycoprotein in different histopathological types and grades of primary hepatocellular carcinoma. AB - To study the effect of the different interventional treatment on P-Glycoprotein (Pgp) in different histopathological types of primary hepatocellular carcinoma (PHC), 98 surgically and histologically verified PHC specimens were obtained. The patients included 57 patients treated by surgical resection alone and 41 patients receiving second-stage surgical resection after four kinds of interventional treatment. SABC immunohistochemical staining with a monoclonal antibody against human Pgp was used to observe the Pgp in all specimens. The positive rate of Pgp was 100% in group of chemotherapy alone (P < 0.05), 62.5% in group of chemotherapy combined with iodized oil (P > 0.05), 46.6% in group of chemotherapy combined with iodized oil and spongia gelatini absorbens (Sga) (P > 0.05), 18.18% in group of chemotherapy combined with Ethanol-iodized-oil and Sga (P < 0.05) and 52.63% in group of surgical resection alone. The positive rate of Pgp varied with different histopathological types, with rate of clear cell PHC being the lowest, and that of poorly differentiated or undifferentiated PHC the highest. The positive rate of Pgp was increased as pathological grades increased. Overexpression of Pgp may be responsible for the intrinsic and acquired drug resistance of PHC. Multidrug resistance (MDR) varied with different histological types. Therapy of PHC should be tailored according to individual. Local chemotherapy combined with ethanol-iodized-oil and Sga embolization may become a new way to overcome MDR of PHC. PMID- 11215059 TI - Effect of vagotomy on acute pancreatitis in rats. AB - One hundred and eighty-two SD rats were randomly divided into the normal control group, fast operating group and food-intake operating group. The experimental model of acute pancreatitis (AP) in rats was established by injecting 5% sodium taurocholate into the pancreatic duct of rat according to Aho's method. The sandostatin was used for positive contrast. The concentrations of serum amylase, calcium, C reaction protein (CRP) and interleukin-6 (IL-6) were assayed respectively at different time points. The pathological sections were observed. Each operating group contained 10 rats. The mortality of the operating groups was observed during the 24 h. The serum amylase level in the AP rats was reduced after receiving vagotomy (VG, P < 0.05). Although the serum calcium level in most groups was decreased, the reduction in the group with VG plus sandostatin was not obvious (P > 0.05). The increase of CRP and IL-6 was not obvious after VG (P > 0.05). The change of mortality was not significant (P > 0.05). The pathological sections showed that the AP pathological change was mild after VG. The disease condition of food-intake operating group was more serious than that of fast operating group. It was suggested that VG had some influence on the prognosis of AP in rats. PMID- 11215060 TI - Isolated pelvic hyperthermochemotherapeutic perfusion--an experimental study on isolating efficacy. AB - Hyperthermochemotherapeutic perfusion model through isolated pelvic vessels was developed to evaluate the leakage of hyperthermia and drugs (such as adriamycin) from the isolated pelvic circulation to systemic circulation and its associated side/toxic effects. The isolated pelvic circulation was perfused through a femoral artery catheter with hyperthermic (48 degrees C to 55 degrees C) adriamycin solution (50 micrograms/ml) for 30 min. The efflux was drained through a femoral vein catheter. And the pelvic temperature was kept at the level of 43 +/- 0.5 degrees C. The temperature of pelvic circulation was kept at 4 degrees C to 5 degrees C greater than the systemic/core temperature. The adriamycin concentration of pelvic efflux was 12 to 46 folds of that of systemic serum. The difference between them was very significant (P < 0.001). As the perfusion pressure was increased, which kept lower than the mean systemic artery pressure, the leakage of the adriamycin from the isolated pelvic circulation to systemic circulation was increased, but there was no significant difference between them (P > 0.05). During isolated perfusion, the systemic blood dynamics remained stable and there were no organic injuries on the important organs. It was suggested that the isolating efficacy of the modality of isolated pelvic hyperthermochemotherapeutic perfusion through vessels was rather high. The hyperthermia and drugs could be effectively limited in the isolated pelvic region with minor side effects on the systemic circulation and important organs. PMID- 11215061 TI - Bovine calcined bone for the repair of radial defect in a rabbit model. AB - In order to investigate the bovine calcined bone's ability of repairing segmental bone defect and seek a new artificial bone substitute material, the bovine calcined bone (450 degrees C, 32 h) was implanted into the 10-mm middle radial defect of rabbits with tricalcium phosphate ceramics as the control. By using the methods of histology, radiology and biomechanics their osteogenic ability were measured. It was found that the bovine calcined bone's ability of repairing bone defect was better than that of tricalcium phosphate ceramics. The histological Nilsson's scores at 3rd, 5th, 9th week after operation were significantly increased (P < 0.01). At 12th week after operation the bending strength of radius in experimental group was much higher than that of control group and turned normal. It was suggested that bovine calcined bone is an ideal artificial bone substitute material with good ability of repairing segmental bone defect and some degree of mechanical strength. PMID- 11215062 TI - The role of neutrophil activation in pathogenesis of preeclampsia. AB - To investigate the effect of neutrophil activation on pathogenesis of pre eclampsia, neutrophil activation was examined by using flow cytometry to assess the CD11b expression and the levels of plasma endothelin-1 (ET-1) and serum NO2- were also measured by using non-equilibrium radioimmunoassay and by Griess assay in 29 pregnant women with pre-eclampsia and 31 normal pregnant women at third trimester. The expression of neutrophil CD11b was significantly elevated in women with pre-eclampsia as compared with that of normal pregnant women at third trimester. The mean fluorescence index of CD11b was 438.38 +/- 179.91 and 326.97 +/- 170.14 respectively (P < 0.05). The plasma ET-1 level and serum NO2- concentration in pre-eclampsic women (63.69 +/- 48.33 pg/ml and 20.03 +/- 4.77 mumol/L, respectively) were both significantly increased as compared with those in the normal pregnancy women (29.98 +/- 20.25 pg/ml and 15.47 +/- 5.47 mumol/L, respectively, P < 0.01). The neutrophil CD11b expression was significantly elevated in pre-eclampsia. The increased neutrophil activation may cause the damage of vascular endothelium and result in NO release compensatory increase in endothelial cells, suggesting that the neutrophil activation may play a key role in pathogenesis of pre-eclampsia. PMID- 11215063 TI - Pre-clinical experimental studies of indomethacin-releasing copper intrauterine device. AB - Effects of two types of intrauterine device (IUD) on the prostaglandins and endothelin (ET) in uterus and on the endometrial morphology in rats and rabbits, and Cu2+ releasing amounts of both IUDs in vitro were observed. The results showed that the inhibiting action of the indomethacin-releasing copper IUD (FICu IUD) on the PGI2 was stronger than that on the TXA2, the ratio of 6-keto-PGF1 alpha/TXB2 was reduced with the increase of the doses. There were significant differences between the groups. The FICu-IUD could inhibit the rising of the ET level and lighten the endometrial impairment caused by the FCu-IUD, and promote copper ion release. It was suggested that indomethacin released by FICu-IUD could effectively reduce abnormal uterine bleeding. PMID- 11215064 TI - Metabolism of dauricine and identification of its main metabolites. AB - To study the metabolism of dauricine in vivo and in vitro and identify the structure of its main metabolites, urine of rats after drug administration as the samples of dauricine metabolism in vivo was studied. Rat liver S9 fraction was prepared and the oxygenation metabolism system reconstituted to perform phase I reaction of dauricine in vitro. TLC, HPLC-DAD and MS were used to analyze and identify dauricine and its main phase I metabolites in the samples. The results showed that besides the untransformed dauricine, in the urine samples there was little product of X' which had the same features of TLC, HPLC-DAD and MS as those of N-desmethyl dauricine (N-ddau). Part of dauricine could be transformed to a main metabolite X after incubating with S9 fraction in appropriate conditions. The molecular ion peak of X was m/z 611. The full scan MS2 spectrum of m/z 611 peak from S9 sample were m/z 580, m/z 566, m/z 552, m/z 206, which were same as those of N-ddau. Liver is the major organ for dauricine metabolism and part of dauricine is biotransformed by liver. The major metabolite is considered to be N ddau. PMID- 11215065 TI - Preliminary studies on the application of retinal thickness analyzer in the diagnosis of glaucoma. AB - The patients with glaucoma underwent the examination of retinal thickness analyzer (RTA) to explore the diagnostic value of RTA in glaucoma. The retina of 6 mm x 6 mm size (approximately 20 degrees, centered on the macula) at the posterior pole was scanned by using RTA to obtain the images in 35 eyes of 22 patients with glaucoma. The images were processed by using SAS software package. The retinal thickness in the patients with glaucoma showed diffuse or local thinning. Twenty-seven eyes was definitely diagnosed as having glaucoma. There was a very significant difference in retinal thickness measurements by RTA between normal group and glaucomatous group (P = 0.0012). Except the measurements at the detected point 6 having no difference, the measurements at the detected point 3 showed a significant difference and the remaining 7 detected points presented a very significant difference between the two groups. Of the detected 9 points, the changes at the points 4, 8, and 9 were the most obvious. The discrete analysis was performed on the glaucomatous patients by a discriminant function established through the data at the detected points 4, 8 and 9 and the accurate estimate rate for the diagnosis of glaucoma was up to 80.77%. The measurements of RTA examination was consistent with the results of the vision field test. It was suggested that diffuse or local thinning of retinal thickness exists in the patients with glaucoma. The temporal inferior arcuate fibers and the papillomacular bundle between the macular and optic nerve heads showed a serious damage. The sensitivity of RTA examination was higher than visual field test. PMID- 11215066 TI - Toxicity of magnetic albumin microspheres bearing adriamycin. AB - Magnetic albumin microspheres bearing adriamycin (ADM-MAM) is a novel chemotherapeutic compound with site-specific drug delivery characteristics. The acute and subacute toxic tests of the compound, local irritating test and anaphylactic test were performed on mice and guinea pigs. The results showed there was no macroscopically and microscopically direct cytotoxic injuries of the compound to the animal organs or to the cells. The LD50 value of the compound was higher than that of the single used adriamycin, indicating that the compound was less toxic than the single adriamycin and quite safe in its therapeutic dosage. Furthermore, there was also no side effects or toxic reactions to be observed on clinical patients with advanced carcinoma or gastric cancer. PMID- 11215067 TI - Change of coagulation factor VIII and antithrombin III activity in bank-stored blood. AB - Coagulation factor VIII and antithrombin III activity were detected in 15 health donors. It was found that antithrombin III activity decreased obviously 12 h after blood drawing. It lost 56% of the activity at the 3rd day, and 70% of the activity at the 7th day. FVIII:c showed no obvious change after 24 h, until the 3rd day. It lost 40%-60% of the activity after 36 h and was reduced to the 30% of the original activity at the 5th day. Our results suggested that at the 3rd day coagulation factor VIII of bank-stored blood can be used to replenish antithrombin III, while bank-stored blood in one day can be used to replenish F VIII. PMID- 11215068 TI - Measuring up. Analyzing control and comparison charts. PMID- 11215069 TI - Protocols for information-driven surveys. PMID- 11215070 TI - Random unannounced surveys in 2001. PMID- 11215071 TI - Survey ready. Brushing up on competence assessment. PMID- 11215072 TI - Ask the experts. How behavioral restraint standards don't apply in your organization. PMID- 11215073 TI - Safety watch. Preventing fatal falls. PMID- 11215074 TI - Private healthcare. Let's drink to that. AB - The Commission for Health Improvement will have authority to monitor private hospitals treating NHS patients. The private sector will be subject to the NHS complaints procedure. The issue of medical staffing for private hospitals needs to be addressed. The uneven spread of private facilities across the country undermines the partnership. Arrangements to cut NHS waiting lists will reduce demand for private medical insurance. PMID- 11215075 TI - More frills than skills. PMID- 11215076 TI - US healthcare. Small add. PMID- 11215077 TI - Commissioning. When push comes to shove. AB - A study of four HAs in three regions found that they had little influence on encouraging trusts to implement the recommendations of the Changing Childbirth report over the period 1993-98. Where changes had been introduced this was often through the influence of an opinion leader in the trust, such as directors of midwifery. The results suggest healthcare professionals providing services have substantial influence over the fate of strategic change initiatives. PMID- 11215078 TI - Caring for diverse populations of HIV-infected patients. PMID- 11215079 TI - New bedfellows? PMID- 11215080 TI - When HIV is not the only diagnosis. PMID- 11215081 TI - Influenza vaccination does not accelerate HIV infection. PMID- 11215082 TI - Scientists at the Children's Hospital, Los Angeles, begin HIV gene therapy trial [news]. PMID- 11215083 TI - HIVMA recruiting health professionals dedicated to HIV. PMID- 11215084 TI - AIDS-related Kaposi sarcoma trial is under way. PMID- 11215085 TI - Women's health. The role of gender in HIV progression. AB - Recent studies have examined the experience of women and the potential for gender differences with respect to HIV progression and the acceptance, tolerance, adherence, and response regarding HAART. Differences in CD4 cell count and viral load have not been reported in all studies. For any given CD4 cell count, women may be at a higher risk of HIV progression. Women appear to have an increased risk of progression to AIDS compared with men with the same viral load. They have lower initial viral loads than men in early-stage disease, but these catch up in advanced-stage disease. Because of depression and other psychological factors, women may be in greater need of supportive services, and this can affect the success of antiretroviral therapy. Women also have an increased risk of adverse drug reactions from HAART. Gender should be considered when prescribing therapy. PMID- 11215086 TI - HIV clinical trials in correctional settings: right or retrogression? AB - The right of incarcerated prison and jail inmates to health care is protected by the 8th and the 14th amendments of the Constitution, respectively. Does the right to health care include access to clinical trials? At the time of this writing, clinical trials have become part of the fabric of HIV/AIDS care, allowing patients to participate in studies of new and often lifesaving treatments. Participation in trials can also be dangerous, as illustrated by the recent death of a subject in a gene therapy trial. This danger is compounded by ethical dilemmas that can arise from the large amount of financial support for clinical trials (greater than 75%) that is derived from for-profit corporations. Indeed, clinical trials are the subject of grave concern on the part of the United States Government, which has recently taken steps to shore up human subject safeguards. Following a conference on the conduct of clinical trials in correctional settings, the Office for Human Research Protections suspended prison research conducted by 4 prestigious academic institutions. PMID- 11215087 TI - IRB/FDA requirements relevant to HIV/AIDS clinical trials in correctional settings. AB - Federally funded research involving inmates in US correctional facilities requires the approval of the Office for Protection from Research Risks (now called the Office for Human Research Protections [OHRP] and located in the Office of the Secretary of the Department of Health and Human Services). Trials that are carried out by pharmaceutical companies (not federally funded) fall under the jurisdiction of the FDA. This article reviews OHRP and FDA guidelines relevant to the conduct of HIV/AIDS clinical trials in correctional settings. PMID- 11215088 TI - Diagnostic and therapeutic dilemmas of a large scrotal lesion in an AIDS patient. AB - In the setting of HIV infection, chronic genital ulcerations may be challenging both diagnostically and therapeutically. The differential diagnosis of these lesions is very broad, and the causes can be multifactorial. We present a case of a chronic, extensive, ulcerating scrotal mass and review the salient clinical, diagnostic, and therapeutic considerations. PMID- 11215089 TI - World AIDS Day 2000: commentary by US United Nations Ambassador. PMID- 11215090 TI - Public perceptions. The generation claim. AB - There is a growing perception that support for the NHS is falling off among the young. The evidence for this is not conclusive. Dissatisfaction with the NHS is more likely to be linked to increased expectations rather than lack of social solidarity. PMID- 11215091 TI - Mental health. Eye off the ball? PMID- 11215092 TI - Cross-border care. Travellers' checks. AB - Interest in the costs of non-emergency operations in different countries is likely to growas movement increases between European Union countries. There are huge variations in the cost to the state of the same operation in different countries. These may influence where services are purchased in the future. PMID- 11215093 TI - Data briefing. Outpatient waiting. PMID- 11215094 TI - Cleaning. In a domestic vacuum? PMID- 11215095 TI - Procurement. Let's spend the cash together. PMID- 11215096 TI - Catering. Fancy that. PMID- 11215097 TI - Bedside TV/telephones. Pillow talk. PMID- 11215098 TI - [Molecular diagnosis and new gene engineering in hematological malignancies]. AB - Advancement molecular diagnostics in hematological malignancy has provided us with a broad menu of new assays and techniques. By integrating the data gleaned from these techniques we can formulate a more rational broad-based diagnosis. Hematological malignancies have traditionally been classified by morphological criteria. However, molecular advances have provided new insights in the genetic backbone of chimeric genes. These malignancies have shown chromosome abnormalities of translocation with chimeric genes, and revealed the rearrangement of chimeric genes by PCR analysis and quantitative PCR system. This review summarized the recent technology for detecting chimeric genes along with concepts of laboratory performance. PMID- 11215099 TI - [Quality assurance of the molecular diagnostic tests in hematological malignancies]. AB - Analyses of nucleic acid sequences in hematological malignancies are now essential in managing patients with hematological malignancies. Because of the impact of the test on decision-making in patient care, its accuracy is quite important. Detection of BCR-ABL mRNA by polymerase chain reaction, one of the most popular molecular diagnostic tests for hematological malignancies, has been used for diagnosis of Philadelphia-positive leukemias. Quality of the test must be assured in the process of diagnostic plan, sampling, measurement(nucleic acid isolation, amplification, detection), report and interpretation. Risk of false positive results due to contamination of in vitro nucleic acid amplification reactions can be decreased through the use of protocols for contamination control. False-negative results may be caused by variability in BCR breakpoint, and loss or degradation of RNA due to inappropriate procedures as well as an insufficient detection sensitivity. Presence of inhibitors of amplification is also to be considered as a cause of false-negative results. Thus, quality control techniques such as internal standards are mandatory to ensure efficient amplification as well as RNA extraction. For the precise evaluation of minimal residual diseases, accurate and sensitive quantitative analyses are required. For quality assurance of assays in the present status of no commercially available kits, it is particularly important to monitor the clinical validation of the results by correlating them with the patient's status to prove clinically relevant. Staffs need to be trained to be familiar with both molecular pathogenesis and technology so that they can provide informative test results with a high quality. PMID- 11215100 TI - [A report on staff development in advanced knowledge and technology of gene diagnosis for medical technologists by the Japanese Association of Medical Technologists: the view of medical technologists]. AB - With advancement of the molecular biology, gene diagnosis is widely utilized in clinical application of medicine. For medical technologists, it is necessary to receive continued education to practice such advanced scientific trends. The Japanese Association of Medical Technologists established a working group for a staff development program of gene diagnosis and chromosome analysis in 1996, and has continued its activities in making inquiries about the present conditions, publishing a textbook, and providing seminars. The internal laboratory utilization of gene diagnosis was 8.7%(213 of 2437 hospitals). Based on the fact that about half of the hospitals use external laboratory, staff development for the internal utilization of gene diagnosis is an urgent issue. We have been providing seminars to meet the educational needs of our members. In addition to those activities, we have continued our efforts in providing a manual with clinically useful information, standardizing methods, establishing an information network, and conducting a controlled survey. The role of the working group is now shared by the local prefecture to further increase the numbers of those with expertise in gene diagnosis. We, medical technologists, need to have a global view of professional growth, and also to cooperate with academic societies related to gene diagnosis to establish a certification system. PMID- 11215101 TI - [Past, present and future of optical cards for medical use]. AB - In the hospital, the chart is an important medical information record. However, it is not easy to refer to chart records. Although a computer is useful in referring to the chart, the most critical defect is the lack of exchangeability between hospitals. An optical card is a new medium for medical use. It has a large capacity for electronic storage, low price and high security. Therefore, the author considers this card a second medical chart. As another card, there is the IC card, which has some limitations in medical use. Although both systems are being examined experimentally, there is no actual practice in the medical field. The reason for this lack of wide use, it is thought that these systems are not yet supported by national health insurance. PMID- 11215102 TI - [Development of perinatal management system using optical card and regional health information network]. AB - In Kagawa Prefecture, a perinatal management system using the optical medical card and the information network has been introduced since October 1998. Four hospitals(Kagawa Medical University, Sakaide Municipal Hospital, Uchinomi Town Hospital and Tsuda Prefectural Hospital) are connected with each other through the health information network(Kagawa Health and Welfare Information Network) organized by Kagawa Prefecture. (http://www.hw.kagawa-swc.or.jp/net/) Patients' clinical data are described on the optical card based on the "standard format of the Japan Association of Obstetricians and Gynecologists(JAOG). (http://www.jaog.or.jp/JAPANESE/MEMBERS/JOUHOU/H10/index.htm). Clinical information including the fetal heart rate(FHR) and sonography (JPG) can be easily transmitted through this network(on line). Without the network, patient data can also be transmitted using the optical card(off line). There are still many technical and social problems to be solved in the future, research into the use of medical information network should be continued. PMID- 11215103 TI - [On standardization of optical memory cards]. AB - An optical card optimizes recording of medical data since it has a large memory capacity, data cannot be interpolated by the addition method, and data are protected from disruption by magnetic force or static electricity. Now that international standards have been established for the card, reader/writer control, and data management, a highly-compatible optical card system for medical use can be fabricated. The optical card is expected to play an important role in the social system as a promising medium for recording or exchanging individual health data, which is anticipated to grow in the near future. PMID- 11215104 TI - [Digital filling system for medical image data]. PMID- 11215105 TI - [What should a laboratory physician expect from a microbiology laboratory?]. AB - Remarkable changes are affecting the discipline of Clinical Pathology/Laboratory Medicine in Japan. Laboratories are changing from revenue centers to cost centers that have many serious problems(ex. closure of the clinical laboratories in the hospitals and outsourcing of laboratory tests due to restructuring in response to economic aspect, limited numbers of certified laboratory physicians, and other factors). And many clinicians in university hospitals do not know what they should expect correctly from the microbiology laboratory. Therefore, we, laboratory physicians and medical technologists must modify our behavior effectively and establish a good collaborative partnership with physicians, nurses and other health care professionals. The microbiology laboratory should provide information that will affect clinical management guidelines for obtaining specimens, microbial identification, antimicrobial susceptibilities, reporting of data and educational updating. Leadership and management skills must be increasingly critical to the success of laboratory physicians in and outside of academic centers. PMID- 11215106 TI - [Results of a questionnaire survey about "standardization" of connection methods in Laboratory Automation System or Laboratory Information System by the National University Hospital Clinical Laboratory Divisions]. AB - "Standardization" is very important in the field of clinical laboratory medicine. Enzyme reference materials(ERM) and standard plasma proteins(CRM470) have already been developed. Reference methods for some clinical chemical tests have also been developed. We are studying "standardization" of electric communication methods between computers and automatic analyzers in Laboratory Automation System(LAS) or Laboratory Information System(LIS). We present the results of a questionnaire survey of 73 LAS or LIS making Companies in this paper. Although "standardization" of electric communications or local area network in LAS or LIS has been done in only 22 companies(34.9%), we are planning more functional standard electric communication methods such as Health Level 7(HL7) or American Society for Testing and Materials(ASTM). PMID- 11215107 TI - [Pathophysiological roles of angiotensin in the pathogenesis of hypertension and cardiovascular remodeling]. AB - Angiotensin(Ang) II plays an important role in regulating cardiovascular hemodynamics and structure. Multiple lines of evidence have suggested the existence of Ang II receptor subtypes, and at least two distinct receptor subtypes have been defined on the basis of their differential pharmacological and biochemical properties and designated as type-1(AT1) and type-2(AT2). Most of the known effects of Ang II in adult tissues are attributable to the AT1 receptor. Recent cloning of the AT2 receptor contributes to reveal its physiological functions. Accumulating evidence demonstrates that the function and signaling mechanism of these receptor subtypes are quite different, and these receptors may exert opposite effects in terms of cell growth and blood pressure regulation. Growth inhibitory effects of AT2 receptor are unique in that this receptor activates a variety of phosphatases and cross talks with the signaling of other seven-transmembrane, G protein-coupled receptors as well as other classes of growth factor receptors. To further examine the role of the AT2 receptor, we generated the AT2 receptor knockout mouse using homologous recombination. Here, we review recent advances in the roles of AT1 and AT2 receptors in the pathogenesis of hypertension and the cardiovascular remodeling. PMID- 11215108 TI - [Positional cloning of the gene(WFS1) for Wolfram syndrome]. AB - Wolfram syndrome(DIDMOAD syndrome) is an autosomal recessive neurodegenerative disorder characterized by juvenile-onset, insulin-requiring diabetes mellitus and optic atrophy. Other symptoms including diabetes insipidus, neurosensory deafness, urinary tract and neurological abnormalities are often accompanied. In patients, beta-cells are selectively lost from their pancreatic islets of Langerhans. The gene was previously mapped to 4p16.1. By haplotype analysis and recombination mapping in 5 families, we localized the gene within a region less than 250 kb on chromosome 6p. In the region, we identified a novel gene(WFS1) encoding a putative transmembrane protein. Mutations were identified in all affected members of the families and these mutations were associated with disease phenotype. This finding was further confirmed by other investigators and to date, more than 50 mutations were identified in the WFS1 gene from the patients with Wolfram syndrome. The WFS1 gene encodes a protein of 100.3 kDa with 9 to 10 putative transmembrane domains. The protein appears to be important in the survival and maintenance of normal pancreatic beta-cells and neurons. Physiological function of the WFS1 protein and mechanisms by which defective WFS1 lead to the development of Wolfram syndrome need to be clarified. PMID- 11215109 TI - [Technology and application of DNA array]. AB - Recently DNA macro and micro array has just begun to use for analysis of DNA expression. The array technique allows us to analyze expression pattern of several hundreds and thousands of genes simultaneously. The array method enables us to analyze gene expression levels of each gene among different samples, however it does not provide comparative analysis of the expression level of multiple genes in a single array. Because intensity of each signal on the array is normalized by the expression intensity of several standard house keeping genes, intensity of signals of each genes among different array can be compared by the number of relative intensity based on normalization. Such characteristic feature of array allows us to analyze potential function of the genes even though function of genes are not known or well characterized. PMID- 11215110 TI - [Habitual abortion and high frequency of low frequent X chromosome monosomy mosaicism: detection by interphase FISH analysis of buccal mucosa cells and lymphocytes]. AB - FISH analysis using X alpha satellite probe was performed to the nuclei of lymphocytes obtained from fourteen women with having a history of habitual abortion for unknown causes(WHA) and from 65 normal control women(NW), in order to determine whether low frequency X monosomy mosaicism is one of the factors of habitual abortion. In parallel, the nuclei of buccal mucosa from 8 of WHA and 65 NW were also examined. Five hundreds of the interphase nuclei in each sample were observed. As results, the frequency of X monosomy in NW found in the lymphocytes or buccal mucosa was ranged from 0-3.2%(mean 1.59%, SD 0.69%) or from 0-3.2%(mean 1.24%, SD 0.85%), respectively. However, the occurrence of X monosomy in WHA was significantly higher compared with that of NW; i.e., 0.8-5.8%(mean 3.21%, SD 1.67) for lymphocytes, and 1.8-7.4%(mean 4.45%, SD 1.73%) for buccal mucosa. These results allowed us to define the reference intervals to discriminate WHA from NW were less than 2.97% or 2.94% for lymphocytes or buccal mucosa, respectively. Based on the reference intervals defined above, the high frequency of X monosomy mosaicism was actually found in 9 of 14 WHA. These results altogether strongly suggested that the low frequency X monosomy mosaicism was one of the factors of habitual abortion. PMID- 11215111 TI - [Epidemiological evaluation of Serratia marcescens isolates in one Japanese hospital during the two years from April 1997 to March 1999]. AB - One hundred fourteen isolates of Serratia marcescens from different patients in Showa University Fujigaoka Hospital during the 2 years from April 1997 to March 1999 were investigated in this study. The isolation frequency(37%, 43 of the isolates) of O-serotype 14(O14) was highest among the 16 different serotypes, and that(24%, 27 of the isolates) of O2 was secondarily highest, while these types were frequently isolated from patients in the surgical ward. O14 with major bacteriocin types 4 and 9(B4 and B9, respectively) showed resistance to piperacillin, the third and fourth generation cephems, new quinolones and aminoglycosides except gentamicin tested. However, O2 with major B1 and B5 showed much greater sensitivity to the antimicrobial agents tested than O14. Furthermore, O2 and O14 were frequently isolated from patients' sputa(41%, 11 of the 27 isolates) and urine(72%, 31 of the 43 isolates), respectively. These findings suggested that S. marcescens O14 with B4 and B9, more resistant to various agents, and O2 with B1 and B5, more sensitive to various agents, show a tendency to inhabit the urinary and respiratory tracts in the hospital patient's body, respectively, having a high risk of hospital infection. PMID- 11215112 TI - [Positive rate of anti-mitochondrial antibody in Japanese corporate workers]. AB - Anti-mitochondrial antibody(AMA) has been reported to be detectable in approximately 85% of patients with primary biliary cirrhosis(PBC). Therefore, a test for AMA is acceptable to be essential for diagnosing PBC. However, the positive rate in Japanese general population has not yet been determined. We tested sera from 1,145 corporate workers who took an annual health check and evaluated the liver of AMA-positive subjects. An indirect immunofluorescence method was used for screening AMA. ELISA and immunoblotting method were used for detecting anti-M2 in AMA-positive cases. AMA was detected in 5 of 1,145(0.44%) corporate workers. AMA positive rate was higher in females than in males(0.91% and 0%, respectively) and the AMA-positive people are all females over age 40. All of the AMA-positive sera are also positive for Anti-M2. Liver biopsy was performed in two AMA-positive cases and the histology was compatible with PBC in both cases. PMID- 11215113 TI - [A Warthin's tumor showing extensive necrosis]. AB - Warthin's tumors are one of the most easily recognizable tumors using light microscopy. However, histopathological diagnosis is difficult in a few cases when characteristic cystic cavities with papillary walling and underlying lymphoid stroma are obscured by reactive changes. We describe a case of an extirpated Warthin's tumor of the right parotid gland which demonstrated extensive necrosis, squamous metaplasia and xanthomatous inflammation. No characteristic structure for this tumor was noticed in a section of an initially sampled specimen. As a result, a destroyed fistula was suspected. An additional sampling was performed to confirm the diagnosis and the sampled specimen fortunately demonstrated the diagnostic structure of a Warthin's tumor excluding malignancy. An awareness of the morphological variation seen in this tumor should lead to additional sampling of specimens, thereby preventing erroneous interpretation. PMID- 11215114 TI - [B precursor lymphoblastic leukemia/lymphoma manifested at onset as hemophagocytic syndrome]. AB - A 20 year-old male patient was admitted to our department for the treatment of recurrence of fever and pancytopenia developed despite of temporal remission of hemophagocytosis syndrome that had been treated with large doses of methylprednisolone in our hospital. Superficial lymph nodes were not palpable. CT scan and echography revealed neither findings of splenohepatomegalia or enlargement of intraabdominal lymph nodes. Bone marrow aspiration showed an increase of histiocytes, the cells phagocytizing erythrocytes and platelets, and a negative test for peroxidase stain. Analysis of surface antigens showed that 11.3% of cells were blast cells positive for CD10, CD19, CD20, CD34 and TdT. Bone marrow biopsy revealed a localized increase in tumor cells positive for L26, CD10 and negative for UCHL-1. Because of the absence of detectable tumor masses and the difficulty in differentiating between malignant lymphoma and lymphatic leukemia, we diagnosed the condition as B precursor lymphoblastic leukemia/lymphoma. If diagnosed with malignant lymphoma preceded by hemophagocytic syndrome(LAHS), he might have a rare type of LAHS-associated malignant lymphoma since histological examination did not reveal diffuse large cell lymphoma, a condition found in most patients with LAHS-associated malignant lymphoma. Whereas if diagnosed as ALL, he was the first adult patient with ALL with HPS at onset as far as we know. In any of these possibilities, the case was considered rare. PMID- 11215115 TI - [On bone and joint diseases]. PMID- 11215117 TI - [Pathoetiology of chronic rheumatoid arthritis--from inflammation to bone destruction. 1) from the viewpoint of clinical genetics]. PMID- 11215116 TI - [Molecular mechanism of bone metabolism]. PMID- 11215118 TI - [Pathoetiology of chronic rheumatoid arthritis--from inflammation to bone destruction. 2) From the viewpoint of immunology]. PMID- 11215119 TI - [Pathoetiology of chronic rheumatoid arthritis--from inflammation to bone destruction. 3) From the viewpoint of pathology]. PMID- 11215120 TI - [Physiopathological interpretation and progress in diagnosis and therapy. 1. Osteoarthrosis]. PMID- 11215121 TI - [Physiopathological interpretation and progress in diagnosis and treatment. 2) Gout and pseudogout]. PMID- 11215122 TI - [Physiopathological interpretation and progress in diagnosis and treatment. 3. Infectious arthritis]. PMID- 11215123 TI - [Physiopathological interpretation and progress in diagnosis and treatment. 4. Psoriatic arthritis and ankylosing spondylitis]. PMID- 11215124 TI - [Physiopathological interpretation and progress in diagnosis and treatment. 5. Relapsing polychondritis]. PMID- 11215125 TI - [Physiopathological interpretation and progress in diagnosis and treatment. 6. RS3PE syndrome]. PMID- 11215126 TI - [Pathophysiological interpretation and progress in diagnosis and treatment. 7. Steroid-induced osteoporosis]. PMID- 11215127 TI - [Physiopathological interpretation and progress in diagnosis and treatment. 8. Steroid-induced osteonecrosis]. PMID- 11215128 TI - [New therapeutic approaches. 1. Non-steroidal anti-inflammatory agents and selective COX-inhibition]. PMID- 11215129 TI - [New therapeutic approaches. 2. New anti-rheumatic drugs: with special reference to methotrexate]. PMID- 11215130 TI - [New therapeutic approaches. 3. Current status and overview of biological products]. PMID- 11215131 TI - [Diagnosis and treatment of diseases with the major symptoms involving the bone and joints: discussion]. PMID- 11215132 TI - [Lemierre syndrome with extensive cervical venous thrombosis and multiple pulmonary embolisms]. PMID- 11215133 TI - [Salmonella infection with endophthalmitis and arthritis]. PMID- 11215134 TI - [An autopsy case of intravascular malignant lymphomatosis treated with combination chemotherapy]. PMID- 11215135 TI - [Recurrent retroperitoneal fibrosis associated with hyperglobulinemia]. PMID- 11215136 TI - [Successful rescue from fatal pulmonary thrombo embolism by percutaneous thrombectomy: a report of two cases]. PMID- 11215137 TI - [Adrenal incidentaloma (including Cushing's syndrome)]. PMID- 11215138 TI - [Mechanism for bile acid transport--recent progress]. PMID- 11215139 TI - [The proposal of the activities of daily living (ADL) index for institutionalized older adults]. AB - The purpose of this study was to propose the ADL index constructed with a unidimensional scale based on item difficulty for institutionalized older adults. Six hundreds and three subjects (159 males and 444 females) were divided into the following four groups based on assisting devices for movement: G1 did not use assisting devices for movement; G2 used a stick or a walker; G3 used a wheelchair; G4 could not move. As the results of examinations from the points of the approximation of proportions, non-answer rates and agreement rates of each item according to 74 ADL items representing 9 ADL domains, the 27 ADL items were selected as utility items. The reliability and unidimensionality of the ADL index consisting of 27 items were considered to be high. As the results of examining the difficulty of items and ADL ability characteristics of each group, the ADL concerning movement and other lower limb activity in G1 and G2, and concerning changes of posture and manual activity in G3 and G4 were considered to reflect the individual differences of ADL ability, respectively. The numbers of ADL items which should first be assessed in each group were as follows: 20 items in G1; 21 items in G2; 21 items in G3; 11 items in G4. PMID- 11215140 TI - [Effects of low concentration of styrene monomer vapor on pregnancy]. AB - To investigate the effects of exposure to styrene vapor on pregnancy, mice proved to be pregnant were exposed to 0, 2, 20 and 100 ppm styrene continuously for 24 hours during the period from day 0 to day 15 of gestation. A special small exposure chamber which can accurately maintain a constant low concentration of styrene vapor was made and used in the experiment. 1) In the 100 ppm group, hyperkinesis was presented in the chamber during the exposure period and inhibition of body weight gain was found (p < 0.01). No deaths occurred in any of the groups. 2) At necropsy of dams, no significant difference was found between the styrene exposed groups and the control group in any of the fertility indices, number of implantations, number of live fetuses, percentage of resorptions, or in the percentage of dead fetuses. The 100 ppm group showed lower fetal and placental weights (p < 0.01). 3) Gross necropsy of dams in the 100 ppm group showed significantly decreased adipose tissue. The liver, kidney and spleen weights were also low (p < 0.01). 4) When exposed to 100 ppm, which corresponds to 5 times the permissible concentration, i.e., 20 ppm, for 24 hours, non pregnant dams showed no abnormality, while pregnant dams showed inhibition of body weight gain and significantly lower fetal and placental weights and maternal organ weights. Therefore, careful consideration should be given to exposure of women of childbearing age to styrene. PMID- 11215141 TI - [A study on the trend of tuberculosis in an area of Shanghai City using mathematical model]. AB - A widely-used mathematical model (compartmental model) in epidemiological studies was utilized to analyze the tuberculosis situation in area Y of Shanghai from 1971 till 1994. In this model, the whole population was divided into 5 groups, (susceptible, latent, prevalent, healed and immune). Six parameters (effective BCG coverage, immune loss rate, infection rate, disease risk, cure rate and heal loss rate) were introduced and discussed to describe the transmission of tuberculosis. The computed tuberculosis data from this model agree quite well with the observed data. The results show that the susceptible group is the largest among all groups. In 1994, the annual risk of infection was estimated to be 0.26%. It is predicted that elderly people will comprise an increasing percentage of tuberculosis patients in the future. It is also found that it will still take a long time to eliminate tuberculosis under current medical situations. PMID- 11215142 TI - [Smoking behaviors among medical doctors in Fukui, Japan]. AB - This study was conducted in order to identify the smoking prevalence among all doctors (N = 874) belonging to the medical associations in Fukui Prefecture and factors that might possibly indicate causal smoking habits. A survey was conducted from December of 1996 to February of 1997, using a self-administered questionnaire, and the response rate for the survey was 91%. The main results of this survey were as follows: The prevalence of smoking among male and female medical doctors was 28% and 8% respectively, which was lower than that of adults in the general population, but higher than that of doctors in the developed countries. The prevalence of smoking among doctors was almost highest when they were 20 to 29 years old, and that among medical practitioners with their own institution was higher than doctors employed by an institution. In particular, medical practitioners who did not smoke were more likely to restrict or ban smoking in their hospitals or clinics. PMID- 11215144 TI - [Telomere heterochromatin in yeast]. PMID- 11215143 TI - [Serotonin transporter]. PMID- 11215145 TI - [Oxidized galectin-1 is a new type factor to promote nerve regeneration]. PMID- 11215147 TI - [DNA replication mechanism in Archaeal cells]. PMID- 11215146 TI - [Malignant transformation and regulation of cell division by a Rho exchange factor ECT2]. PMID- 11215149 TI - [beta-D-xyloside-initiated oligosaccharides in cultured cells]. PMID- 11215148 TI - [Juxtacrine and matricrine--the other ways of growth factor actions]. PMID- 11215150 TI - [Biogenesis of iron-sulfur clusters]. PMID- 11215151 TI - [Molecular mechanism of biological clock: for chronobiological approach to stress]. AB - Recent progress in molecular chronobiology revealed that the clock genes control intracellular feedback loops. CLOCK protein and BMAL1 protein, first discovered as components of the circadian clock in mammals, are known to function as transcriptional activators in the circadian feedback loop of drosophila. PERIOD and TIMELESS proteins work as inhibitors for these activators in drosophila and possibly in mammals. The clock genes described above are also expressed in peripheral tissues with circadian rhythmicity. Cultured rat-1 fibroblast shows circadian expression of clock genes after serum shock or forskolin stimulation. These results indicate that the clock genes function not only as components of the endogenous clock, but also as a coordinator of the circadian activity of peripheral tissues. It will be important to study stress from the aspect of circadian rhythm. PMID- 11215152 TI - Functional dissociation of striatal and hippocampal cholinergic systems in egocentric and allocentric localization: effect of overtraining. AB - The effects of overtraining on the retention of egocentric localization (EL) and allocentric localization (AL) tasks using rats injected with 1.8 nmol/12 microliters of ethylcholine mustard aziridinium ion (AF64A) in the striatum or hippocampus were examined. In the EL task, an arm positioning at in same direction of a randomly selected start arm was baited throughout trials. In the AL task, a baited arm was fixed throughout trials regardless of the position of the start arm. The performance of EL retention was disrupted only by intrastriatal AF64A injection. The overtrained striatal lesioned animals showed better performance compared to the non-overtrained striatal lesioned animals. In contrast, hippocampal AF64A injection selectively impaired AL retention. Unlike the effect of overtraining on EL retention in striatal lesioned animals, however, the AL performance of hippocampal lesioned animals was not significantly affected by overtraining. The results support the idea of functional dissociation of striatal and hippocampal cholinergic systems in EL and AL learning and provide further evidence that the striatal cholinergic system may be involved in the memory (consolidation or retrieval) process of EL learning, and the hippocampal cholinergic system in the processing of specific cues necessary for efficient performance in AL learning rather than memory. PMID- 11215153 TI - The effects of zolpidem and zopiclone on daytime sleepiness and psychomotor performance. AB - Zolpidem (ZLP), which has selective affinity to the BZ1 (omega 1) receptor and a short half-life, is a novel hypnotic. The objective of this study is to compare the residual effects of standard clinical doses of ZLP and zopiclone (ZPC), a short-acting hypnotic marginally selective for the BZ1 (omega 1) receptor, given in a single dose on daytime sleepiness and psychomotor function. This study was carried out as a double-blind cross-over study with 10 mg ZLP, 7.5 mg ZPC and a placebo in 12 healthy male adults. In the multiple sleep latency test, sleep latency was not reduced but increased by ZLP and ZPC as well as the placebo when drug plasma levels had nearly reached the peak. Subjects administered ZLP were significantly more feeble, lethargic and antagonistic in mood rating scales than those administered ZPC. The incidence of severe behavioral side effects was higher in the case of ZLP than in the case of ZPC over the same period. Sleep latency the next morning was significantly shorter in the case of ZPC than in the case of ZLP or the placebo. The tapping test performed at the same time demonstrated that the number of taps was significantly less in the case of ZPC than in the case of ZLP or the placebo. The results of the present study suggest that ZLP acts more rapidly than ZPC. On the other hand, ZLP has less residual effect on sleepiness and psychomotor function the next morning. PMID- 11215154 TI - [Formation mechanisms of stress adaptation: role of functional coupling of glucocorticoids and brain serotonergic nervous system]. AB - It is known that the incompetence of stress adaptation mechanisms is a primary factor affecting disorders such as anxiety and depression. Increased clinical evidence indicates that hyperactivity of the hypothalamo-pituitary-adrenal (HPA) axis and dysfunction of the brain serotonin (5-HT) nervous system are risk factors associated with these disorders. Given the high sensitivity of hippocampal 5-HT responses to glucocorticoids, functional changes in the hippocampal 5-HT nervous system induced by chronic hypercorticism are attracting more attention. Repeated exposure to stress stimuli or chronic administration of corticosterone produces hippocampal 5-HT1A receptor dysfunction as well as an imbalance in mineralocorticoid and glucocorticoid receptors. We recently demonstrated that activation of the 5-HT1A receptors facilitates the adaptive responses to stress stimuli by acting on the HPA axis. These findings suggest that abnormal coupling of glucocorticoid-mineralocorticoid/glucocorticoid receptors-5-HT1A receptors in the hippocampus may be one factor disrupting adaptation to stress situations. Moreover, it is shown that activation of the coupling system affects learning and memory processes associated with stress stimuli. These findings suggest that the functional coupling of glucocorticoid mineralocorticoid/glucocorticoid receptors and serotonergic neurons in the brain may play a significant role in the recognition of stress stimuli and induction of stress adaptation, and dysfunction of this coupling system may be related to the onset of affective disorders. PMID- 11215155 TI - [Influence of stress on learning and memory]. AB - This paper describes the influence of stress on learning and memory. The mice receiving inescapable electroshock fail to perform the active conditioned avoidance response of lever-pressing. This is called learned helplessness, which is ameliorated by treatment with antidepressants including one of the selective serotonin reuptake inhibitors (SSRIs). It is of particular interest that posttraumatic stress disease (PTSD) accompanied by memory impairment could be improved by treatment with SSRIs. The different kinds of stress including ischemia, footshock, psychological stress, and forced swimming influence learning and memory as indexed by spontaneous alternation performance as well as passive avoidance learning. In addition, a variety of stresses influence the activity of hormones and neurotransmitters like monoamines, neuropeptides, and excitatory amino acids resulting in changes in learning and memory. Finally, the accumulation of data is necessary to clarify the exact mechanism of stress on learning and memory. PMID- 11215156 TI - [Influences of chronic stress on central nervous systems]. AB - Chronic mild or moderate stress elicits an adaptive change in central nervous systems that function to maintain homeostasis. The principal components of stress response are the extrahypothalamic corticotropin-releasing hormone (CRH) and the locus coeruleus (LC)-norepinephrine (NE) systems. CRH is known to produce various stress-, anxiety- and arousal-associated behaviors in animals. Moreover, CRH causes an increase in the firing rate and activity of tyrosine hydroxylase in the LC, and NE release in LC projection areas. It is thought that chronic inescapable and unpredictable stress can result in a sustained dysregulation of both CRH neuronal activity and LC-NE systems. One may hypothesize that the NE-CRH interaction occurs in the terminal projection of forebrain NE systems, the hypothalamic paraventricular nucleus (PVN), the bed nucleus of the stria terminalis (BNST) and the central nucleus of the amygdala (CeA) where NE stimulates CRH release. Such CRH-NE-CRH feed-forward systems elicit progressive augmentation of stress responsivity with repeated exposure. The beta-adrenergic receptor down-regulation is induced by acute and chronic exposure to moderate and predictable stress, implying an adaptation to stress. However, chronic unpredictable (variable) stress (CVS), a model for depression, up-regulated the beta-AR. In our laboratory, we found that concurrent treatment with the selective serotonin reuptake inhibitor (SSRI) citalopram caused beta-R down-regulation in the frontal cortex of rats treated with CVS for 14 days. As previously reported by the authors, an increase in 5-HT availability plays a role in preserving beta R down-regulation by NE potentiating agents. In depressed patients, hyperactivation of the CRH-NE systems caused by the CRH-NE feed-forward system is thought to be involved in generating anxiety, sympathetic activation and hyperarousal. Moreover, a decrease in the 5-HT turnover in depressed patients has been reported. Accordingly, it is proposed that an increase in 5-HT availability by SSRI might contribute to normalize beta-R down-regulation as an adaptive regulatory mechanism against excessive CRH-NE neurotransmission under a "stressful" situation. PMID- 11215157 TI - [Future trends in the treatment and diagnosis of rheumatoid arthritis]. PMID- 11215158 TI - [Therapeutic efficacy of cyclosporin A in four cases of amyopathic dermatomyositis with rapidly progressive interstitial pneumonia]. AB - OBJECTIVES: We investigated the clinical features of amyopathic dermatomyositis (ADM) with rapidly progressive interstitial pneumonia (IP), and the effectiveness of cyclosporin A (CsA) for IP. METHODS: In our four patients who were accorded with the notion of amyopathic dermatomyositis proposed by Euwer and treated with CsA for IP, and eight reported patients for whom we could obtain details of the clinical course, we investigated the relationship between the clinical features of them at the start of CsA administration and the clinical effectiveness of CsA. RESULTS: When we investigated the effectiveness of CsA in our four patients and eight reported patients, we could judge that effective cases were four and ineffective cases were eight. We compared the PaO2 at the start of CsA administration between effective and ineffective cases, the average PaO2 at the start of CsA administration was 65.7 mmHg in four effective cases, while it was 51.0 mmHg in eight ineffective cases. There was a statistically significant difference between the groups. CONCLUSIONS: Because our results suggested that many ineffective cases were treated with CsA after they had developed severe respiratory failure, we think that CsA should be given to ADM patients with rapidly progressive IP before the progression of respiratory failure. PMID- 11215159 TI - [Interrelationship between disease activity and nutrient intake or serum cytokine in patients with rheumatoid arthritis]. AB - OBJECTIVE: This study was designed to investigate the possibility of nutrition guidance for patients with rheumatoid arthritis (RA). We studied interrelationship between disease activity and nutrient intake or serum cytokine concentration in patients with RA. METHODS: Dietary survey was performed to assess nutrient intake of RA patients. Disease activity parameters, such as weariness index, arthritically index and QOL index were evaluated by self questionnaire. CRP and serum cytokine concentrations were measured. Interactions between these parameters and nutrient intake were analyzed. RESULTS: In comparison of nutrient intake between patients with RA and healthy controls, RA patients indicated lower ratio of polyunsaturated to saturated fatty acid (P/S) than controls. Preceding with the analysis between disease activity parameter and nutrient intake, RA patients were divided into two groups according to their activities. High weariness group indicated higher lipid intake and energy supplies from fat than low group, suggesting the relationship between disease activity and lipid intake in RA patients. From the comparative study of serum cytokine concentration between patients with RA and healthy controls, RA patients indicated higher concentration of IL-1 beta, IL-6 and IL-8. Serum concentrations of these proinflammatory cytokines correlated significantly with some nutrient intakes. CONCLUSION: These results imply the relationship between nutrient intake and disease activity in patients with RA. It is important to develop nutrition guidance to improve symptoms for patients with RA. PMID- 11215160 TI - [A case with juvenile rheumatoid arthritis who developed cerebral vasculitis and venovascular hypertension]. AB - On November, 1997, a 15-year-old boy visited our hospital because of headache, fever and arthralgia. He was treated with 5 mg/day of prednisolone thereafter. On October 21, 1998, he was admitted because of remittent fever and multiple arthralgia and diagnosis of juvenile rheumatoid arthritis (JRA) was made. He was also found to have hypertension of 210/110 mmHg, and soon developed ptosis of the eye, facial paresis and perceptive deafness of the right side. Cerebrospinal fluid showed protein of 98 mg/dl and mildly elevated IgG, IgA and IgM levels with normal cell count. Brain MRI examination revealed multiple cerebral lesions in the frontal, parietal and cerebellar areas on the right, whose cause was thought to be vasculitis. Renal angiography demonstrated a right renal artery stenosis, compatible with renovascular hypertension. He was treated with 60 mg of prednisolone per day, which brought about a satisfactory improvement of the above rheumatic and neurologic signs. On November 17, 1998, he received a follow-up study of MRI, which failed to show any cerebral lesions, supporting the effectiveness of prednisolone. An angiotensin converting enzyme inhibitor successfully normalized hypertension and renin activity in serum, although renal blood flow did not increase. PMID- 11215161 TI - [Improvement of cerebral perfusion with argatroban in a patient with antiphospholipid syndrome]. AB - A 22-year old woman developed erythema in her hands. She also suffered from general fatigue and arthralgia. In July of 1992, she visited the dermatology clinic of Nagoya City University Hospital. We made a diagnosis of subacute cutaneous lupus erythematosus with thrombocytopenia and gave her 30 mg of prednisolone daily. Her conditions were improved and had been stable with 5 mg of prednisolone daily. In the winter of 1993, she developed ulcer in her fingers and soles. These lesions were associated with antiphosholipid syndrome. She complained of mild headache. She was examined by CT, MRI and single photon emission computerized tomography (SPECT) using N-isopropyl-p-[123I] iodoamphetamine (IMP). Low perfusion areas in the bilateral occipital lobes and the right temporal lobe were found in SPECT, although no abnormalities were detected by CT and MRI. Low perfusion areas in antiphospholipid syndrome might be caused by microarterial thrombosis, microvenous thrombosis or spasms, although they could be reversible. Ten mg of argatroban daily for one month improved cerebral low perfusion, headache, and skin lesions. In this case, argatroban was effective for both cerebral low perfusion and skin ulcer, which were related to antiphospholipid syndrome. PMID- 11215163 TI - [Origin of the diversity and similarity of pathological manifestations of collagen disease: lessons from murine models in an aspect of pathogenomics]. PMID- 11215162 TI - [A case of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) related glomerulonephritis associated with systemic sclerosis treated by steroid pulse therapy: a case report]. AB - A 57-year-old woman had been diagnosed as systemic sclerosis (SSc) with Raynaud's phenomenon, acrosclerosis and polyarthritis since 1995. She admitted to our hospital in July 1996 because of general fatigue, hemosputa and progressive renal insufficiency. On admission, the blood pressure was normal and laboratory findings showed elevation of the serum creatinin level and a high titer of the myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) (> 1000 EU). The renal biopsy revealed crescentic glomerulonephritis. Both renal insufficiency and high titers of MPO-ANCA improved remarkably after methylpredonisolone pulse therapy. This case was suggestive of elucidating the pathogenesis of SSc and MPO ANCA related glomerulonephritis. PMID- 11215164 TI - [Rheumatoid arthritis and secondary amyloidosis]. PMID- 11215165 TI - [Should we change some medical terms in rheumatology]. PMID- 11215166 TI - [Dawning of laboratory automation; individually constructed automated systems]. AB - In the early stages of laboratory automation, the first step toward automation was the use of a spectrophotometer equipped with a flow cell system. Then, automated machines were introduced. Furthermore, computing systems, which are necessary for automated machine systems, contributed to advances in laboratory automation. Under these primitive conditions, we devised a data processing system for clinical biochemistry and further advanced the first stage of automated laboratory system. These automated systems have gradually matured in to a total laboratory automation system. As described in this report, we designed and developed an automated system in our laboratory. PMID- 11215167 TI - [Present state and development of the network communication system]. AB - Information technology is a dynamic technology that has sparked the development of many new products and new services and the medical field is not an exception. We would like to introduce our new service which started in December 1999, and is called "SNCS". Connecting Laboratory and Sysmex by a dedicated network, SNCS provides services such as 'On-line QC' and 'On-line Support' to support Laboratory technicians. PMID- 11215168 TI - [Developmental frontier of a modular automated system]. AB - The clinical laboratory is faced with increasing problems such as healthcare reform, cost pressure and increased laboratory regulations. Despite these problems, the users have even higher expectations for laboratory services. To resolve these issues, the clinical laboratory must become more efficient by incorporating creative solutions and adapting to changes. One key word is increased automation of laboratory procedures and integration of automated systems. First, automation will reduce the dependence on manual labor. Second, laboratories could perform a larger menu of tests in-house. This not only reduces expense but also reduces the turn around time for testing. To realize cost reduction and reduce turn around time, we propose the Modular system. PMID- 11215169 TI - [Tele-micro-surgery system]. AB - This paper describes a master-slave type tele-micro-surgical system with an intelligent user interface. To enhance the accuracy and the rigidity of the slave manipulator, multi-circular guides were adopted for the degrees of rotational freedom. To increase the operability of the system, an "anti-shadow" technique was used and the 3D relative information was presented on a 2D display. Furthermore, the anti-shadow was processed using a real-time tracking vision system to guide the slave-manipulator to the target position automatically. Multi axis force information was converted into auditory information to transmit the reality of the surgical field. It took approximately 25 minutes to suture a 1 mm diameter artificial micro-blood-vessel using the system. The carotid artery of a rat with a diameter of 0.3 mm was also successfully sutured. PMID- 11215170 TI - [Advances in the clinical laboratory automation system of Akita University Hospital]. AB - Abstract Clinical laboratory automation, which was widely discussed in the 1960's, was developed in late he 1970's. The computerized automatic analyzing system for clinical laboratories spread nationwide in the 1980's. Akita University Hospital was established in 1971. We have been making efforts to establish the automated clinical laboratory system. The hematological and clinical chemistry divisions were automated in 1981. In 1988, in order to establish a fully automated clinical laboratory, we introduced sample-conveying systems in each division including hematological, clinical chemistry, urinalysis, serological and immunological divisions. In 1998, we connected the sample conveying systems which had been separately established in each division to create a fully automated clinical laboratory with an integrated sample-conveying system. PMID- 11215171 TI - [Investigative application of a laboratory database]. AB - An end user computing system (EUC) is usually part of the laboratory information system. Effective use of this EUC system is described in this article. The first application of this system is for monitoring the turn-around time (TAT) of laboratory work flow. Precise time sequential data were analyzed using this end user computing system. Weekly fluctuations of TAT depended on the cyclic changes in requisition numbers of test samples. Another application of EUC was phenotype screening of genetic abnormalities. Screenings from high triglyceride and low HDL cholesterol were effective for the phenotype screening for genetic lipoprotein lipase abnormalities, and phenotype screening from high albumin cholinesterase ratio was effective for genetic abnormalities causing silent cholinesterase. Investigational application of EUC was demonstrated in two areas of laboratory research. PMID- 11215172 TI - [The new generation of laboratory automation systems]. AB - Laboratory automation is essential to release laboratory technicians from simple routine work, allowing them to make use their time for more skilled tasks. In 1998, we developed a Total Infection Control System called "Dr. Fleming", and would like to introduce it into practical use. This systems is expected to help physicians by providing highly valuable test results and useful information. PMID- 11215173 TI - [Development of blood cell measurement]. AB - Automated blood cell analyzers used in hematology laboratories are required to measure many specimens rapidly and efficiency has been realized through increasing the measurement parameters and throughput volume in one instrument. In the period of 1950's through the early part of 1960's, only red blood cells and white blood cells could be counted. In 1965, Technicon Corporation developed an instrument which can measure the number of blood cells, hemoglobin, hematocrit and calculate corpuscular constants simultaneously. Thereafter, the methodologies for simultaneous platelet measurement and precise determination of blood cell distribution have been developed. Then, the development of new reagents has achieved three part differentials in the distribution of white blood cells. Thanks to this development, microscopic white blood cell differentials has been replaced by blood cell analyzers in screening tests. Though blood cell analyzers may be further improved by expanding of the number of parameters available for simultaneous measurements, meeting social needs in the new era will not be possible without the creation and realization of new concepts employing new technologies such as IT (Information Technology). PMID- 11215174 TI - [Building bridges toward the 21st century]. AB - Just as Rome was not built in a day, there are few great inventions and discoveries that can be made overnight. There are always historical circumstances behind them. Laboratory Automation is not an exception. With the end of World War II in 1945 as a turning point, a large volume of American medicine was introduced all over Japan, and clinical laboratory testing which was imported at the same time has taken root and matured. As a result, we can now carry out prompt and fully automated laboratory testing second to none at many hospital laboratories. In this paper, I recall the development and summarize the expansion by focusing on clinical laboratory automation as it has developed in the latter half of the 20th century in Japan. I would feel amply rewarded for my efforts if this paper proved helpful to the young generation. The clinical laboratory of the 21st century rests on their shoulders. PMID- 11215175 TI - [Recent trends in the standardization of laboratory automation]. AB - Laboratory automation systems have been introduced to many clinical laboratories since early 1990s. Meanwhile, it was found that the difference in the specimen tube dimensions, specimen identification formats, specimen carrier transportation equipment architecture, electromechanical interfaces between the analyzers and the automation systems was preventing the systems from being introduced to a wider extent. To standardize the different interfaces and reduce the cost necessary for the laboratory automation, NCCLS and JCCLS started establishing standards for the laboratory automation in 1996 and 1997 respectively. NCCLS has published five proposed standards which that are expected to be approved by the end of 2000. PMID- 11215176 TI - [Communications among components of automated clinical laboratory systems]. AB - Laboratory Automation Systems has been developed with original specifications from each vender. To construct a system in a multi-vender environment, remodeling of the interface and software had to be done by the user. The standard concerning automated laboratory systems was made by NCCLS in 1997. This standard provides a protocol for communications among Laboratory Automation Systems(LAS), Laboratory Information Systems(LIS), automated instruments (analyzers), and pre- and post analytical automated devices. This document explains the current details and the overall content of the communication standards for automated laboratory systems developed by the NCCLS Subcommittee on Communications between Automation Systems. PMID- 11215177 TI - [Standardization of barcodes used for sample identification]. AB - In the clinical laboratory, they are mainly using one-dimensional barcode (simply, barcode) for the sample identification. It has been proposed an international standard for the barcode by NCCLS with the cooperation of JCCLS and CODE128 was selected for its symbol. Other details for it also can be found in this article. The committee of JSCC has started to discuss a barcode for the next generation so that more information can be conveyed on test tubes. A two dimensional symbol barcode (2D barcode) is one system. NCCLS is interested in this act and therefore cooperation is anticipated in the development of international standards. PMID- 11215178 TI - [Standardization of operation monitoring and control of the clinical laboratory automation system]. AB - Laboratory automation systems showed up in the 1980s and have been introduced to many clinical laboratories since early 1990s. Meanwhile, it was found that the difference in the specimen tube dimensions, specimen identification formats, specimen carrier transportation equipment architecture, electromechanical interfaces between the analyzers and the automation systems was preventing the systems from being introduced to a wider extent. To standardize the different interfaces and reduce the cost of laboratory automation, NCCLS and JCCLS started establishing standards for laboratory automation in 1996 and 1997 respectively. Operation monitoring and control of the laboratory automation system have been included in their activities, resulting in the publication of an NCCLS proposed standard in 1999. PMID- 11215179 TI - [Pursuit of economic efficiency in the hospital laboratory--full automatic re test system of clinical chemistry, hematology, immunology and cost control system]. AB - Further business improvement is requested due to finance-based fluctuation and the influence of the revision in the medical treatment law. Therefore, new laboratories are needed. To achieving this in our hospital, economic efficiency is being pursued. The first issue is the use of space, the second issue is labor saving. The third issue is the simplification of business procedures. There is individual quality control by the zonal verification method that we developed, as well as the quality control of the batch method using controlled substances. The four issue is cost control. By controlling the delivery and use of reagents and materials including the term of validity control, we made an effort to abolition defective stock. The fifth issue is correspondence to circulation style society. The disposal of laboratory garbage is a major issue. We controlled garbage that occurs unnecessarily. Furthermore, we are improving the demand for reagents that exceeds the specification and use reagent containers. PMID- 11215180 TI - [Trial digitalization of analog-data obtained from the AutoAnalyzer]. AB - The AutoAnalzer(Basic Model) manufactured on Technicon corporation was a very useful instrument for clinical laboratory automation, but it was necessary to convert the data obtained from the instrument to digital values used the chart reader. This was very troublesome and there was apprehension that there would be errors in A-D conversion. We tried converting data obtained from the AutoAnalzer to a digital value by on-line connection of the instruments with minicomputers(LINC-8 and FACOM-R). The output of the recorder was converted to voltage(0 to 100 V) using a potentiometer, quantitated(0 to 1.000) by the A-D converter attached to LINC-8, and processed by the minicomputer. The control-box was an experimental device mainly designed for the convenience of users. The functions of the control-box were designated analytical items, No. of A-D converters, start and stop of the AutoAnalzer operation to the minicomputer. Employing the control-box, a technician operated this system freely, without direct computer operation. We established a generally satisfactory system for clinical laboratory automation using the minicomputer. PMID- 11215181 TI - [Modularization by the open standard. (I)]. AB - We are proceeding with the project called "Open LA21 Project" in the course of the clinical laboratory automation toward the 21st century. With the modular system that realizes integration, downsizing, a reasonable price, and is the future course in the clinical testing automation system as well, we aim to establish common standards among manufacturers as the only way to create user friendly market environments where the proper competition exists among the manufacturers. The common standards which are in preparation by the participating companies as "Open module system standards" are the standards which are going to be made public. They are intended to guarantee connection, compatibility of the products in conformity with the standards. In this project, we intend to realize the modular system that integrates each field, such as chemistry, hematology, coagulation/fibrinolysis, immunology, urinalysis in an early stage, and contribute positively to restructuring and upgrading the "raison d'etre" of the 21st century clinical testing. PMID- 11215182 TI - [Modularization by the open standard. (II)]. AB - In recent years, accompanied by the marvelous development and spread of Laboratory Automation System(LAS), the NCCLS is now proposing five international standards for laboratory automation. We have based our laboratory on these "NCCLS standards of laboratory automation", we take these standards ahead first, and we now propose an open standard called "Open LA 21", to establish more detailed standard replacing the NCCLS laboratory automation standards. PMID- 11215183 TI - [Visual backward masking in schizophrenia]. AB - Visual backward masking is used to investigate the function of attention as the initial stage of visual information processing by measuring the shortest stimulus presentation time for accurate cognition. This is achieved by applying a masking stimulus after target stimulus presentation. In this study, 50 controls and 50 schizophrenics (paranoid type) were examined by this method. In the control group, 1) there was a significant decline in correct answers to the target stimulus with age; and 2) there was a significant increase in correct answers with repetition. However, in the schizophrenic group, 1) there was a significantly lower number of correct answers in all age groups compared to that in the controls, along with a greater decline in correct answers with age; and 2) there was no increase in correct answers with repetition; 3) good performers among the schizophrenic patients were young with a short duration of illness and on a low dose of medication. Poor performers showed numerous positive and negative psychotic symptoms, were not on medication, or had positive findings on CTscan; furthermore, 4) longitudinal re-examination of the same subjects showed that even when psychotic symptoms improved and the subjects were able to return to society, their ability to give correct answers remained significantly different compared to that of the controls. These findings seem to reflect the trait-dependence aspect of schizophrenia (paranoid type) on a visual backward masking task. Furthermore, visual backward masking seems to be a convenient and useful measure for this aspect of attention and its trait-dependence in schizophrenia. PMID- 11215184 TI - [Study on pancreatic steatorrhea in patients with chronic pancreatitis]. PMID- 11215185 TI - [Autoimmune pancreatitis]. PMID- 11215186 TI - [Prognostic factors of hepatocellular carcinoma: analysis by the proportional hazard model]. AB - Five hundred fifty patients hospitalized to our hospital during 1990 to 1999 were studied. Subjects consisted of 413 males and 102 females and mean age was 62.1 years. Association with HBV infection, HCV infection and both infection was 11.1%, 78.4% and 2.5% respectively. According to the criteria based in Liver Cancer Study of Japan, 5 year survival rate in clinical stage I, II, III was 42.3%, 38.8% and 17.5%. Tumor morphology was nodular type in 78.9%, massive type in 9.1% and diffuse type in 10.5% of cases. Portal tumor thrombus and distal metastasis were observed in 19.9% and 6.3% of all cases. The 1-, 3- and 5-year survival rate in patients received any therapy was 80.8%, 44.6% and 28.7%, respectively. Analysis by the proportional hazard model showed that HBV infection, advanced clinical stage, multiple tumors, a tumor diameter in excess of 5 cm and AFP positivity were shown as significant factors on poor prognosis. PMID- 11215187 TI - [Signet ring cell carcinoma of the colon with monoclonal gammopathy of undetermined significance]. PMID- 11215189 TI - [A case of upper jejunal gastrointestinal stromal tumor (GIST) accompanied with von Recklinghausen's disease]. PMID- 11215188 TI - [A case of true enterolithiasis with acute appendicitis]. PMID- 11215190 TI - [A case of ileal perforation due to intestinal tuberculosis simulating radiation ileitis]. PMID- 11215191 TI - [A case of inflammatory fibroid polyp of the ileum presenting typical findings of intussusception by ultrasonography and computed tomography]. PMID- 11215192 TI - [A case of arteriovenous malformation of the ileum with repeated bleeding]. PMID- 11215193 TI - [Serum soluble interleukin-2 receptor levels in patients with renal cell carcinoma: a comparison of values before and after surgery]. AB - This study was carried out in order to find out whether soluble interleukin II receptor (sIL-2R) levels were useful as a treatment biomarker in patients with renal cell carcinoma (RCC). The subjects consisted of 17 patients with RCC who had been scheduled for radical or partial nephrectomy. Serum levels of sIL-2R were measured before surgery and 1 and 3 months after surgery. We also analyzed the relationship of preoperative sIL-2R to pathologic TNM-stage, grading and presumptive tumor volume. The mean value of pre-operative sIL-2R in patients with RCC was 496.5 U/ml as compared with 302.7 U/ml in the control group (p = 0.056). Pre-operative sIL-2R values were 411.1 U/ml in stage I (n = 6), 481.4 U/ml in stage III (n = 11) and 1,330 U/ml in stage IV (n = 1). There was no significant difference between stage I and stage III. As compared with pathologic grading, pre-operative sIL-2R levels in patients with grade 2 were significantly higher than those with grade 1 (609.8 U/ml versus 288.7 U/ml, p = 0.016). There existed a significant correlation between preoperative sIL-2R and presumptive tumor volume (r = 0.61, p = 0.008). Three months after surgery, sIL-2R values were significantly higher than before surgery. Serum sIL-2R levels seemed to bear some relationship to the extent of disease in patients with RCC. Values of sIL-2R were significantly higher after than before surgery at least for a three-month postoperative period, suggesting a response to trauma of surgery. Further long term studies were required to clarify if sIL-2R could predict the progression of disease. PMID- 11215194 TI - Extracorporeal shock wave lithotripsy for upper urinary tract stones using the Dornier Lithotripter Compact: an experience in Japan. AB - Between May 1997 and February 1998, 40 cases of renal stones and 40 cases of ureteral stones in 60 males and 20 females were treated with the Dornier Lithotripter Compact. The size of the stones ranged from 5 mm to 80 mm. Three patients required epidural anesthesia and 4 patients required a ureteral stent. Fragmentation of the stones was observed in all patients. After 1 month, the efficacy and stone free rates were 91% and 54%, respectively. After 3 months, they were 91% and 68%, respectively. There were no serious side effects such as pyelonephritis, perirenal hematomas, and massive hematuria. In conclusion, the Dornier Lithotripter Compact proved to be a safe and highly effective lithotripter for the treatment of renal and ureteral stones. PMID- 11215195 TI - [Clinical evaluation of urinary basic fetoprotein and the BTA test for detection of bladder cancer]. AB - We compared the results of urinary basic fetoprotein (BFP) and the BTA test with those of urinary cytology in patients with bladder cancer. We also analyzed the urinary BFP and the BTA test results in patients with benign diseases and postoperative bladder cancer with no evidence of recurrence. The cutoff value for urinary BFP was set at 10 ng/ml. Classes 4 and 5 according to urinary cytology were defined as positive. The sensitivity of urinary BFP for Ta, 1 bladder cancer was significantly higher than that of urinary cytology (p < 0.05). The urinary cytology positive rate for Ta, 1 bladder cancer improved when combined with urinary BFP and the BTA test. The urinary BFP positive rate for benign diseases was significantly higher in patients with pyuria than in patients without pyuria (p < 0.05). The BTA test positive rate for benign diseases was higher in patients with pyuria than in patients without pyuria. The urinary BFP and the BTA test positive rates for postoperative bladder cancer with no evidence of recurrence was significantly higher in patients with urinary diversion than in patients without urinary diversion (BFP: p < 0.01, BTA: p < 0.05). PMID- 11215196 TI - [Long-term clinical results of 5 cases of urachal carcinoma]. AB - Five cases of urachal carcinoma experienced in our hospital during the past 20 years are reported. Surgical resection is considered as the first treatment option of this disease, and other therapies to be less beneficial. Complete surgical extirpation and detection of recurrence in the early stage are considered to be important since local recurrence occurs frequently. We enforced the bladder preserving operation for 4 patients with urachal carcinoma except for 1 case with peritonitis carcinomatosa in the initial diagnosis, and multiple surgical treatment was performed again for 2 patients with recurrence. The bladder was preserved with no evidence of malignancy in three patients for 24, 19 and 5 years, respectively. In the initial management of urachal carcinoma, we believe that bladder-preserving surgery should be considered in selected cases though close follow-up is demanded. Herein, we also report the immunohistochemical study of paraffin-embedded specimens using anti-CEA, CA19-9, CA125 and p53 monoclonal antibodies. The positive reaction was observed in 100% (5/5) for CEA, 80% (4/5) for CA19-9, and 20% (1/5) for CA125. These results suggest that CEA may be a useful marker in the diagnosis of this neoplasm and early detection of its recurrence. Nuclear accumulation of p53 was observed in 80% (4/5), but it did not correlate with the disease progression. PMID- 11215197 TI - [A case of primary renal carcinoid tumor]. AB - The patient was a 44-year-old woman in whom a mass of the right kidney was found when she underwent abdominal ultrasonography in a physical checkup. The computed tomography of abdomen and the magnetic resonance imaging of abdomen revealed a 3 x 3 cm solid mass at the right kidney. Excretory urograms showed a deformity of the right collecting system due to a mass lesion. The specimen of the resected tumor showed a cellular arrangement specific to carcinoid tumor and positive reaction of Grimelius stain. Electron microscopy confirmed the presence of dense core granules in the tumor cells. Gastrointestinal investigation after the operation revealed no particular findings suggesting a carcinoid syndrome. No evidence of metastasis or recurrence was noted for 5 months after the operation. This was a very rare case of primary renal carcinoid tumor, representing the 12th case in the literature in Japan. PMID- 11215198 TI - [A case of peripelvic extravasation related to pregnancy]. AB - A 35-year-old woman was hospitalized at 39 weeks 0 days of gestation because of acute left flank pain. Magnetic resonance imaging (MRI) revealed bilateral hydronephrosis with peripelvic extravasation of contrast material around the left kidney. The pregnancy ended with a cesarean section and after the cesarean section a left double-J-stent was placed cystoscopically. An excretory urogram following the removal of the ureteral stent showed no extravasation or hydronephrosis in either kidney. PMID- 11215199 TI - [Metastatic bladder tumor disseminated lymphogenously from gastric cancer: a case report]. AB - A 59-year-old man was referred to our clinic with a complaint of frequent urination, voiding pain, and macroscopic hematuria. He had undergone total gastrectomy for mucinous adenocarcinoma, 21 months earlier. Pelvic computed tomography revealed a thick bladder wall all around. There were no other metastatic sites except for paraaortic lymph nodes. Transurethral resection of the bladder tumor was performed. The specimen showed signet ring cell carcinoma and revealed the same pathological findings as the primary gastric cancer. We diagnosed him with metastastic bladder tumor lymphogenously disseminated from gastric cancer. Such lymphogenous metastases from gastric cancer at the entire bladder wall without other apparent lesions have rarely been reported in the Japanese literature. PMID- 11215200 TI - [A case of neurogenic bladder due to neuro-Behcet disease]. AB - Behcet disease is a systemic vasculitis of unknown cause with variable clinical features. The central nervous system may also be involved in about 10% of the patients with Behcet disease. Half of them show marked central nervous system symptoms and are diagnosed as neuro-Behcet disease. Voiding symptom is seen in about 5% of the patients with neuro-Behcet disease. We report a case of neuropathic vesico-urethral dysfunction in a 39-year-old man with neuro-Behcet disease. Its radiological and urodynamic features and treatment are also presented with some discussion. PMID- 11215201 TI - Venous hemangioma of the scrotum: a case report. AB - We report a case of intrascrotal hemangioma. A 68-year-old man who had noticed a swelling in his left scrotum over the past 1 year was seen at our hospital. Under a diagnosis of intrascrotal tumor, total excision of the mass was performed. Histopathological examination revealed venous hemangioma of the scrotum. PMID- 11215202 TI - [Fournier's gangrene in a patient with malignant lymphoma: a case report]. AB - We report a case of Fournier's gangrene. An 83-year-old man underwent biopsy of left inguinal tumor as an outpatient. Pathological diagnosis was malignant lymphoma (diffuse large cell type). Three weeks later, he developed reddened scrotal swelling accompanied with high fever (> 39 degrees C). On admission, antibiotic chemotherapy was initiated. Although his general condition was improved, scrotal necrosis had developed. A computed tomography scan demonstrated thickened subcutaneous tissue over the left lumbar region. Excision of necrotic tissue and sequential irrigation using povidone iodine liquid were effective. The patient then underwent chemotherapy for malignant lymphoma at the internal department. Nine months after the operation, the scrotal skin had completely recovered. PMID- 11215203 TI - Acute scrotal swelling in Henoch-Schonlein purpura: a case report. AB - Henoch-Schonlein purpura is a systemic vasculitis and sometimes presents as acute scrotal swelling in children. We report a case of Henoch-Schonlein purpura with acute scrotal swelling, which was correctly diagnosed based upon local physical findings. Scrotal ultrasonography showed normal testes and hydrocele testis around the affected testis 3 hours after the sudden onset of the pain. The scrotal symptoms improved in 2 days with steroid therapy. Scrotal ultrasonography was useful to diagnose Henoch-Schonlein purpura with scrotal involvement. Steroid treatment appeared to be effective for this condition. PMID- 11215204 TI - [MN/CA IX antigen as a potential target for renal cell carcinoma]. AB - MN/CA IX is considered as a carbonic anhydrase isoenzyme expressed in the normal alimentary tract in a tissue-specific manner. This antigen is activated in the majority of renal cell carcinomas (RCC) but not in the normal kidney tissues. Our previous study revealed that increase of malignant potential is related to down regulation of MN/CA9. To investigate the mechanism of MN activation in RCC, we examined the methylation status of this gene (MN/CA9) in RCC cell lines (SKRC-1, 6, 10, 12, 14, 44, 59). Moreover, we analyzed the circulating blood of patients for the presence of RCC cells by RT-PCR, to determine whether detection of circulating RCC cells could be useful as a biomarker. CpG methylation was investigated at 7 CpG sites in the MN/CA9 5' region. Clear mRNA signals were observed in 5 cell lines (SKRC-1, 6, 10, 44, 59), e.g., MN/CA9 positive. These 5 MN-positive cell lines showed hypomethylation in the 5' region. In contrast, all CpG sites were methylated in the remaining 2 lines and 3 normal kidney tissue samples. These results suggest that hypomethylation in the 5' region may play an important role in the expression of MN/CA9 in RCC. RT-PCR analysis of blood samples from RCC patients revealed the presence of circulating MN-positive cancer cells in the blood. Although a significant correlation with tumor stage and grade was not observed, the analysis of blood samples from patients with metastases resulted in a high detection rate of 82%. These findings suggest the usefulness of MN/CA IX as a potential diagnostic marker for detection of RCC. PMID- 11215205 TI - [Significance of chromosome 9 alterations as an initial step in urothelial carcinogenesis]. AB - One of the most important features of urothelial cancers of the bladder and upper urinary tract is metachronous and/or synchronous multifocal occurrence with high frequency. Since such multifocal recurrent tumors are derived from a common transformed cell, the chronological tracing of genetic alterations in such multifocal tumors may reveal the precise timing and role of genetic alterations in urothelial carcinogenesis. In this study, we tested the presence of microsatellite alterations in synchronous and/or metachronous multifocal urothelial cancers to examine the chronological genetic alterations for the presence of hierarchy of genetic alterations in urothelial cancer development. Genetic alterations at 20 microsatellite loci on 8 chromosomal arms (2q, 4p, 4q, 8p, 9p, 9q, 11p, and 17p) were tested. Judging from the patterns of allelic deletion and microsatellite shifts, multifocal tumors in at least 21 (81%) of the 26 evaluable patients were considered to be derived from a single progenitor cell. In patients with multifocal tumors of an identical clonal origin, discordant microsatellite alterations were observed at significantly lower frequencies on chromosome 9 compared with those on the other chromosomes tested. The heterotopic spread and genetic divergence may occur long before the clinical manifestation of multiplicity from a single transformed cell. The data strengthens the previous view that heterotopic spread of transformed progenitor cells and genetic divergence occur after chromosome 9 alterations in most of urothelial cancers. PMID- 11215207 TI - [Clinical role of cell cycle regulators in androgen-dependent cancer cell growth]. AB - The functional and quantitative alterations in cell cycle regulators after androgen depletion in an androgen-dependent cancer cell and the interaction between androgen receptor and cell cycle regulators were examined in order to clarify the initial response of cancer cells to anti-androgen therapy. Fluorescence activated cell sorter analysis (FACS) of androgen-dependent cancer cell line (SC-3) cells cultured with or without 1 nM dihydrotestosterone (DHT) revealed that suppression of cell growth after androgen withdrawal was due to G1 arrest. The protein level of cyclin D1 decreased without any apparent change in the amounts of Cdk2, Cdk4, cyclin E or cyclin A. Among various Cdk inhibitors (CKIs) examined, p27 was upregulated at both mRNA and protein levels 24 h after androgen depletion. On the other hand, cyclin E has been shown to increase the transactivation activity of the human androgen receptor (AR) in the presence of DHT. These results suggest that cell cycle regulators are critical targets in the initial response of androgen-dependent cancer cells to androgen depletion and play a key role in the transcriptional activity of AR. PMID- 11215206 TI - [Human heparanase: roles in invasion and metastasis of cancer]. AB - Heparanase, which is an extracellular matrix degradative enzyme, degrades heparan sulfate and heparan sulfate proteoglycans, which are chief components of extracellular matrix and vascular basement membrane. The gene structure of this enzyme was recently determined. The biological functions of this enzyme in vivo were as follows: 1) this enzyme accelerates cancer cell invasion and metastasis though the degradation of vascular basement membrane and extracellular matrix by cancer cells; 2) this enzyme releases and activates heparin-binding growth factors such as bFGF and VEGF from heparan sulfate proteoglycans, and induces angiogenesis; 3) the degradative products of heparan sulfate proteoglycans by this enzyme suppress the biological function of activated T-lymphocytes. Therefore, heparanase is thought to be a favorable molecule for acceleration of cancer invasion and metastasis. The expression of heparanase is strongly correlated with the metastasis of melanoma and fibrosarcoma. Thus, heparanase may play important roles in invasion and metastasis of cancer. PMID- 11215208 TI - [Role of hepatocyte growth factor in invasion of prostate cancer cell lines through tumor-stromal interaction]. AB - We examined how prostate stromal cell-derived hepatocyte growth factor (HGF) affects invasion of prostate cancer cells through tumor-stromal interaction. The effects of HGF, various growth factors [transforming growth factor (TGF)-alpha, TGF-beta 1, basic fibroblast growth factor, keratinocyte growth factor, and platelet-derived growth factor], and conditioned medium (CM) from prostate stromal cells (PrSC) on prostate cancer cells (LNCaP, PC-3 and DU145) were determined by collagen gel invesion assay. DU145 cells and PrSC were co-cultured for matrigel invasion chamber assay. LNCaP and PC-3 cells did not respond to any of the factors examined. Invasion of DU145 cells into the collagen gel matrix was induced by HGF and TGF-beta 1, but not by any of the other factors tested. When DU145 cells were cultured in CM from PrSC or co-cultured with PrSC, the cells acquired invasive potential, and this invasion was inhibited by an antibody against HGF, but not against TGF-beta 1. Induction activity of CM from cancer cells to stimulate HGF production by PrSC was studied by ELISA method and Western blotting. Native type HGF production in PrSC was enhanced by some unknown inducer(s) produced by cancer cells. In summary, PrSC-derived HGF enhanced invasive activity of the prostate cancer cell line DU145 through tumor-stromal interaction wherein DU145 cells secreted some HGF-inducer(s) for PrSC. PMID- 11215209 TI - [Correlation between expression of metastasis-related genes and lymph node metastasis in testicular cancer]. AB - To investigate the factors related to lymph node metastasis of testicular germ cell tumors, we first established a seminoma orthotopic model with lymph node metastasis in SCID mice by inoculating small fragments from subcutaneous xenografts. Second, we compared the expression patterns of metastasis-related genes of the seminoma xenografts and of the TCam-2 cells which were established as a seminoma cell line from a primary testicular seminoma. Third, we immunohistochemically analyzed human germ cell tumors (25 seminomas, 17 nonseminomas) using monoclonal antibodies to CD34, VEGF, VEGF-C, Flt-4, MMP-2 and E-cadherin. Testicular seminoma xenografts grew in 32/32 (100%) of the inoculated mice, of which 15 (47%) developed macroscopic metastasis to the renal hilar lymph node. Circulating tumor cells were detectable by using a PCR assay for the human beta-globin gene in 25/32 (78%) mice, although metastatic foci were not histologically evident in the visceral organs, including lungs, liver, kidneys and spleen. This may reflect the lymphophilic characteristics of the seminoma cells used. Regarding mRNA expression of metastasis-related genes, an increased expression of MMP-2 and VEGF compared with that in the s.c. xenografts was demonstrated by RT-PCR assay in the testicular seminoma xenografts. In addition, uPAR, MMP-1, MMP-2, MT1-MMP and MT3-MMP showed a a stronger expression and PAI-2 a weaker expression in the seminoma xenografts than did TCam-2 cells. These results suggest a higher metastatic potential of the seminoma xenografts, especially testicular xenografts, as compared with TCam-2 cells. In the immunohistochemical study, a significant correlation was found between MMP-2 expression and lymph node metastasis, which is compatible with the results for the metastasis-related gene expression from the seminoma xenografts. PMID- 11215210 TI - [Methicillin-resistant Staphylococcus aureus infection in the elderly]. PMID- 11215211 TI - [Regeneration of neuronal cells]. PMID- 11215213 TI - [Subcortical dementia in Parkinson's disease]. PMID- 11215212 TI - [Dementia with Lewy bodies]. AB - Dementia with Lewy bodies (DLB), the second most frequent cause of primary degenerative dementias following Alzheimer's disease, has been increasingly recognized since the proposal of the consensus name and clinical diagnostic criteria. Although DLB overlaps in clinical, pathological, and genetic features with Alzheimer's disease and Parkinson's disease, DLB should be understood as an entity with the essential feature of the presence of Lewy bodies in the brain stem and cerebral cortex. From the clinical point of view, DLB is characterized by the presence of progressive dementia without severe memory disorders at the early stage, with significant cognitive fluctuations, well-formed recurrent visual hallucinations, and spontaneous Parkinsonism. This article reviews recent clinical and research findings, including our own, to facilitate clinical recognition of DLB. In addition to the supportive features described in the consortium clinical diagnostic criteria for DLB such as falls and great sensitivity to neuroleptic drugs, our studies found other frequent disorders including disproportionately severe visuoconstructive and visuoperceptual disturbances, transitory alterations in consciousness with reduplication phenomena, misidentification delusions, and non-aphasic misnamings. Neuroimaging features include relatively preserved hippocampal volume on MRI and occipital involvement on metabolic and blood flow imagings. The correct diagnosis of DLB is important to administer adequate treatment, to avoid adverse effects with neuroleptic drugs, and to establish precise prognosis. The present summary of the clinical features is hopefully helpful for clinical diagnosis of DLB. From a therapeutic point of view, cholinesterase inhibitors seemingly show some efficacy in the treatment of cognitive alterations. Further research would result in advances in diagnostic methods and therapeutic approaches in the near future. PMID- 11215214 TI - [Prion diseases]. PMID- 11215215 TI - [Vascular dementia]. PMID- 11215216 TI - [A trial to improve the quality of care in our long-stay chronic care hospital]. PMID- 11215217 TI - [Cooperation of nurse and careworker]. PMID- 11215218 TI - [A focus on activity care]. PMID- 11215219 TI - [End-of-life care in long-term care hospital (facilities)]. PMID- 11215220 TI - [Effect of the level of basic activities of daily living on home caregiver burnout]. AB - To relieve the stress of caregivers, it is critical to identify and classify the burden factors in the elderly patients. In order to determine the factors that exhaust caregivers, a cross sectional survey was done. The study employed a self recording questionnaire form which included the Pines' burnout scale and the level of patient's basic activities of daily living (BADL). Seventy-three caregivers filled in the questionnaire. They reported the difficulty of care for an elderly patient in the home, and the degree of the difficulty correlated well with the burnout score (r = -0.517; p < 0.001). The caregivers' burnout score did not correlate so well with the level of their patient's BADL (r = -307; p = 0.014). Among the factors in BADL, aid for toilet use, feeding, sitting, and transferring raised the burnout scale. On the other hand, assistance for bathing and dressing did not correlate with the burnout score. On multiple regression analysis using the background factors for the burnout score as explanatory variables, aid for feeding and sitting were significant independent contributing factors. Since it became clear that the caregivers in the home were almost burnt out owing to the aid they need to give for the elderly person's BADL, attempts should be done to reduce their burden as soon as possible. PMID- 11215221 TI - [Calcium decreases urinary oxalate]. AB - The effects of calcium supplementation on urinary oxalate excretion was tested in 9 normal subjects, 4 males and 5 females between 23 and 49 years of age. In a crossover study 800 mg calcium was orally administered as active absorbable algal calcium (AAACa) (A) and calcium carbonate (B), and compared with non-calcium containing placebo (C). Calcium, oxalate, osmolality, creatinine and pH were measured in the first three morning urine samples and Ca/osmolality, Ca/osmolality/body weight, Ca/creatinine and oxalate/osmolality were calculated to correct for urine dilution. Ca x oxalate product was also calculated and Ca oxalate crystal in the sediment was microscopically examined and semiquantitatively estimated as -, +, ++, and +++ expressed as 0, 1, 2 and 3 respectively. Urinary Ca excretion was similar in A and B, but significantly larger than C, regardless of the method of correction for dilution. Urinary oxalate excretion tended to be lower in A than in B and C. Urine pH was similar among all three groups. Ca x oxalate product was higher in C than in A and B. AAACa, unlike calcium carbonate, appeared to decrease urinary oxalate excretion and Ca x oxalate product more efficiently than Ca carbonate, suggesting a possibility of inhibiting the formation of Ca x oxalate kidney stones. Formation of calcium oxalate was also tested in vitro by adding oxalate to urine samples and aqueous calcium solution. PMID- 11215222 TI - [Clinical findings of arteriosclerosis and serum lipoprotein(a) concentration in elderly patients]. AB - This study was conducted to evaluate the relationship between arteriosclerosis and lipoprotein(a) [Lp(a)] from the point of view of aging. A total of 354 patients (167 men) aged 60 or more were enrolled and serum Lp(a) levels, vascular risks, and complications were studied. Patients were divided into 3 groups according to age: group I (n = 73: aged 60 to 69), group II (n = 144: aged 70 79), and group III (n = 137: aged 80 or more). Vascular complications were assessed by carotid ultrasonography (US), ECG, and ankle pressure index (API), US findings were stratified according to the distribution of plaque lesions in unilateral and bilateral lesions, while plaque types were subdivided based on the morphology and US echogenicity. Male patients with risk factors (diabetes, hypercholesterolemia, cigarette smoking) as well as stroke were frequent in group I, indicating some selection bias. However, there was no difference in Lp(a) level among the three groups. Carotid lesions, especially bilateral lesions with more thickened plaques, and low API were both significantly frequent in group III. Logistic regression analysis showed that carotid lesions were influenced not only by aging, but also independently by high Lp(a) levels in group III, and by hypertension in group II. A high Lp(a) level was related to hypercholesterolemia and hypoechoic plaque. These findings indicated that atherosclerosis, which developed in both the carotid and peripheral arteries with aging, was related to different risks in each decade of life. Furthermore, it seems that a long period of high Lp(a) levels may promote the formation of hypoechoic plaque. PMID- 11215223 TI - [An autopsy case of anaplastic thyroid carcinoma that transformed from papillary carcinoma within 5 years from initial diagnosis]. AB - An 84-year-old man was admitted to our hospital with right shoulder pain. He had been suffering from well-differentiated papillary thyroid carcinoma since 1994, and had undergone surgery three times, including procedures due to recurrence. Since CT showed a right cervical tumor, recurrence of thyroid carcinoma was diagnosed. He died in September 1999 due to progressive respiratory failure. Autopsy was performed and pathological examination revealed the recurrent tumor and metastatic lesions had totally transformed to anaplastic thyroid carcinoma. Since anaplastic carcinoma is characterized by exceptionally rapid progression with dire prognosis, physicians should be aware of the major risk factors of anaplastic transformation in elderly males aged over 60 years old, with repeated relapses of differentiated carcinoma, and a history of tumor irradiation. PMID- 11215224 TI - [An aged case of bilateral ballistic movement which was thought to be exacerbated by respiratory insufficiency]. AB - We report a 75-year-old man who had shown bilateral ballistic movements. He had suffered from pulmonary emphysema for about 35 years and was treated with oxygen therapy 3 years before. When he was 70 years old, involuntary movements appeared in bilateral limbs. His involuntary movements were ballistic, and become gradually worse. T2-weighted MRI after admission demonstrated high signal intensities in the bilateral pallidum, indicating multiple brain infarcts in the subcortical white matter. Ultrasonography showed 2 plaques in the left common carotid artery. Laboratory studies revealed blood coagulation abnormalities and hypoxia. Medication with clonazepam and tiapride together with oxygen therapy normalized blood gas levels and improved his involuntary movements. But after discharge, he stopped oxygen therapy and involuntary movement became worse again, associated with hypoxia demonstrated by his blood gas analysis. These findings suggest that not only cerebrovascular disease but hypoxia might play an important role in the appearance and exacerbation of involuntary movements. PMID- 11215225 TI - [Relief of subacute herpetic pain and postherpetic neuralgia with repeated application of 10% lidocaine cream]. AB - Analgesic efficacy of repeated application of a lidocaine cream formula was investigated in herpes zoster patients with subacute pain with no further improvement after continued treatment since their acute stage (S-HZ group, n = 23), and in patients to whom past treatments had not provided adequate pain relief (PHN group, n = 28). In both groups, visual analog scale (VAS) values decreased significantly from their corresponding values before the present treatment with few cases of side effects and complete disappearances of the pain in 21.6% of all the patients. The results indicate that the repeated application of the lidocaine cream is a safe and effective treatment method. Significantly higher effectiveness was achieved in the S-HZ group in terms of the difference in the VAS values between before and after the treatment, effectiveness in improving the activities of daily life, and overall efficacy evaluation. PMID- 11215226 TI - [Correlation between prior coronary revascularization and perioperative cardiac events in patients for noncardiac surgery]. AB - We evaluated the influence of interval between prior coronary revascularization and subsequent noncardiac surgery on perioperative cardiac events. We retrospectively identified 162 consecutive patients with previous revascularization procedures who had undergone noncardiac surgery. Postoperative cardiac complications occurred in 10 (6.2%) patients, cardiac death in 1 patient, and significant arrhythmia in 3 patients. These patients had higher rates of unstable angina, myocardial infarction within 3 months, cerebrovascular disease, peripheral vascular disease, renal dysfunction (Cr > or = 1.9 mg.dl-1) and higher preoperative risk scores as described by the Cleveland Clinic (P < 0.05). Also, the incidence of cardiac complications increased when noncardiac surgery was performed within 1 week of previous percutaneous transluminal coronary angioplasty (PTCA) and in more than 5 years after coronary artery bypass grafting or PTCA (P < 0.05). Although PTCA is widely accepted, especially in Japan, early lesion progression was observed during the first several days and atherosclerotic progression was apparent in more than 5 years after the procedure. Therefore, the time between coronary revascularization and noncardiac surgery, as well as atherosclerotic risk factors, is important in evaluating patients with history of previous revascularization procedures. PMID- 11215227 TI - [Anesthetic management of MICS with Port-Access system]. AB - Port-Access system (P-A) is a catheter-based system for minimally invasive cardiac surgery (MICS) characterized by avoidance of full sternotomy with the aid of Endoaortic Clamp Catheter (EAC) for intra-aortic occlusion instead of the conventional external aortic crossclamping. In our hospital, eleven patients underwent MICS using P-A from August in 1998 to the present time. We compared the intra- and post-operative anesthetic management of these patients with that of fifteen patients done by using our conventional MICS method, Saitama Medical School system (SMS). Anesthetic management of these MICS patients is directed toward early extubation, and therefore all patients receive intravenous anesthesia with a small dose of fentanyl combined with inhalational agent or propofol. Without increasing the time of the cardiopulmonary bypass (CPB) and the amount of the intraoperative bleeding, MICS with P-A needs more time to begin CPB than that with SMS because it takes more time to insert these catheters, especially EAC into the suitable position using transesophageal echocardiography (TEE) and fluoroscopy. The time to start CPB must be shortened by skilled cannulation. There is no difference in the postoperative length of ICU and hospital stays between P-A and SMS. In MICS, TEE is the window to the heart for both surgeon and anesthesiologist and used to guide for the placing of the catheters and weaning from CPB, and anesthesiologist should be skillful in using TEE to evaluate the de-airing procedure and assess volume load and contractility of the left ventricle. PMID- 11215228 TI - [Intravenous patient controlled analgesia combined with continuous thoracic epidural analgesia for post-thoracotomy pain]. AB - We compared the efficacy of intravenous patient controlled analgesia of buprenorphine plus continuous thoracic epidural infusion of bupivacaine (IV-PCA group) with the efficacy of continuous thoracic epidural infusion of bupivacaine and buprenorphine (the TEA group). No patient in IV-PCA group required supplemental analgesics, while 90% of TEA group required supplemental intramuscular buprenorphine to relieve post-thoracotomy pain. In TEA group, 94% of the supplemental drugs were administered during night shifts. These results indicate that IV-PCA of buprenorphine combined with continuous thoracic epidural infusion of bupivacaine is more effective analgesic management than continuous TEA with buprenorphine and bupivacaine. PMID- 11215229 TI - [Negative-pressure pulmonary edema associated with transurethral resection syndrome]. AB - We described a patient who had developed negative-pressure pulmonary edema associated with severe transurethral resection syndrome. A relatively healthy, 67 yr-old man (171 cm and 77 kg) with hypertrophic prostate was scheduled for transurethral resection of the prostate under spinal anesthesia. The patient was sedated with continuous propofol infusion because of his anxiety and wish of being asleep. Fifty minutes after starting the operation, electrolyte analysis revealed a decrease in serum Na+ concentration (116 mEq.l-1), and 10 mg of furosemide and hypertonic saline were administered. Thirty minutes later, the arterial oxygen saturation dropped suddenly and arterial blood gas analysis suggested marked pulmonary insufficiency (PaO2: 64 mmHg and PaCO2: 59.4 mmHg). The patient's trachea was intubated and endotracheal release of pinkish foamy sputum was observed. Chest X-ray showed severe lung edema. Massive absorption of the irrigation fluid might have decreased the electrolyte concentration (Na+: 101.0 mEq.l-1) and colloid oncotic pressure. No evidence of cardiac failure was observed immediately after the incidence of pulmonary edema with pulmonary catheter monitoring. The patient's airway was almost intact under spontaneous breathing, but augmented negative-pressure derived from intermittent snoring was considered to be sufficient to break hydrostatic balance of pulmonary capillary vessels and lead to severe pulmonary edema. PMID- 11215230 TI - [Four cases of the anomalous origin of the left coronary artery from the pulmonary artery]. AB - We report perioperative management of 4 patients with anomalous origin of the left coronary artery from the pulmonary artery. This report involves with 3 infant cases and an adult. Two infants underwent coronary reimplantation procedure and Takeuchi's method was performed on the other infant. In all infant cases, mitral valve plasty was performed to correct mitral regurgitation secondary to papillary muscle dysfunction. The adult patient underwent CABG with ligation of LCA. General anesthesia was performed with high doses of fentanyl in all cases. We employed a relatively high PaCO2 and low FIO2 in order to maintain a high pulmonary vascular resistance. It aims to decrease the incidence of left to right shunt. We used epinephrine to wean one infant and the adult from cardiopulmonary bypass. Perioperative course was uneventful with the use of catecholamines and high doses of vasodilators for left ventricular dysfunction and coronary perfusion under mechanical ventilation. PMID- 11215231 TI - [Effect of pre-mixed lidocaine with propofol on propofol injection pain in elderly patients]. AB - The purpose of this study was to compare the younger and older patients in the incidence and the severity of the pain during injection of propofol. Thirty-four, elderly patients (60-80-yr-old) and 52 patients (20-40-yr-old) scheduled to undergo elective surgery were studied. We conducted a prospective, randomized and double-blinded trial. All patients were randomly allocated to one of two groups according to the agents added to 1% propofol 20 ml; Group S, normal saline 2 ml, and Group L, 2% lidocaine 2 ml. The pain on injection was rated as none, mild, moderate, or severe. Seventy percent of patients in the S group of elderly patients experienced pain, while 22% of patients experienced pain in the L group in elderly patients. The incidence of pain on injection in the S group of older patients was comparable with S group of younger patients. The severity of pain in elderly patients was significantly decreased after premixing with lidocaine. There were no significant differences between older and younger patients in the severity of propofol injection pain in both S group and L group. In conclusion, elderly patients suffered the pain on injection of propofol with the same incidence as the younger patients did. Lidocaine premixed with propofol significantly reduces the incidence and the severity of pain associated with propofol in elderly patients. PMID- 11215232 TI - [Anesthetic management of tracheal stent insertion under total intravenous anesthesia--a report of two cases]. AB - Tracheal stent insertion is a useful method for patients with malignant tracheal stenosis. Expandable metal stents were inserted in two patients with severe dyspnea due to tracheal stenosis caused by lung cancer and esophageal cancer. The tracheas were intubated after spraying the pharynx with 4% lidocaine solution. The respiration was assisted. Anesthesia was maintained by intravenous propofol. There were no episodes of coughing during and after the procedure. PMID- 11215233 TI - [Anesthetic management with veno-venous extracorporeal membrane oxygenator (VV ECMO) in a patient with severe tracheobronchial stenosis]. AB - We conducted an anesthetic management to perform tracheostomy and tracheolysis in a 33 year-old female with severe stenosis extending to the lower trachea and right main bronchus. The minimal diameter of the stenotic lesion of the trachea was 3 mm according to the preoperative examinations including tomography, CT scan and magnetic resonance imaging. Since there was a high risk of airway collapse during anesthetic induction that could have made ventilation impossible, we decided to apply VV-ECMO to support gas-exchange prior to anesthetic induction. Blood gas analysis showed good results, and sufficient oxygenation and stable circulation were achieved during surgical procedures. Total intravenous anesthesia with propofol and fentanyl could provide adequate depth of anesthesia during surgery and rapid recovery with good spontaneous respiration after the termination of the infusion. VV-ECMO was a useful method to support gas-exchange in a case not requiring circulatory assistance without uneven oxygenation sometimes observed in VA-ECMO. PMID- 11215235 TI - [Left lung lavage affected the cardiac autonomic nervous activity more than right lung lavage during one lung ventilation in a patient with pulmonary alveolar proteinosis]. AB - A 31-year-old man with pulmonary alveolar proteinosis underwent whole lung lavage using differential lung ventilation under general anesthesia with propofol and fentanyl. Left lung lavage was performed under the differential lung ventilation using extracorporeal lung assist. A month later, right lung lavage was performed under the differential lung ventilation alone. We compared left lung lavage with right one in the effects on heart rate variability and relationships between heart rate and arterial pressure. In the left lung lavage compared with the right one, arterial pressure was maintained higher; sympathetic nervous activity was kept tonic as shown in the power spectral analysis of heart rate variability; coherency showed lower; and a phase relationship analysis indicated a delay of almost 180 degrees. Therefore, we conclude that left lung lavage affected the cardiac autonomic nervous activity more than right one in differential lung ventilation. PMID- 11215237 TI - [Anesthetic management for MIDCAB using the target controlled infusion and the bispectral index]. AB - We report our experience in using the target controlled infusion (TCI) of propofol combined with the bispectral index (BIS) monitoring for anesthetic management of minimally invasive direct coronary artery bypass (MIDCAB) in a 43 year-old-male patient with angina pectoris. After premedication, the patient was connected to the monitor with electrodes for BIS monitor. Then, anesthesia was induced with fentanyl and propofol using TCI technique. When blood concentration of propofol reached 4 micrograms.ml-1, the trachea was intubated. Before starting the operation, we evaluated the relationship between blood concentration of propofol and the value of BIS, and the standard maintenance concentration of propofol was set at 3 micrograms.ml-1. When the concentration of propofol was 3 micrograms.ml-1, the value of BIS was about 60. Anesthesia was maintained with nitrous oxide and oxygen and continuous infusion of propofol using TCI technique. When necessary, we gave additional injection of fentanyl and vecuronium bromide. Furthermore, diltiazem was infused continuously for cardiac rate control, as well as infusion of nicorandil, nitroglycerine for prevention of coronary artery spasms, and prostaglandin. After the operation, the patient was alert in 8 minutes and we could extubate in 12 minutes. The use of TCI combined with BIS monitoring for maintenance of anesthesia for MIDCAB is useful and safe. PMID- 11215234 TI - [Two cases of ischemic changes indicated in the amplitude of motor evoked potentials during thoracoabdominal aortic aneurysm repair]. AB - Monitoring of motor-evoked potentials (MEPs) is employed to examine functional integrity of descending motor pathway during thoracic aortic surgery. We experienced two cases of intraoperative changes in MEPs during thoracic aortic replacement. In one case, MEPs recovered after the intercostal artery reattachment, and in another case after the release of aortic clamping. No postoperative paraplegia was found in both cases. We conclude that monitoring of MEPs is useful not only because we can detect symptoms of the spinal cord injury from ischemia immediately but also because they give us a clue to decide operative procedures. PMID- 11215236 TI - [Anesthetic management for distal aortic arch aneurysm stent grafting]. AB - A 76-year-old woman with thoracic aortic aneurysm involving distal aortic arch was scheduled for graft replacement from ascending to proximal aortic arch with endovascular stent graft to descending aorta. Surgical procedures were performed under median sternotomy with hypothermic systemic circulation arrest and selective cerebral perfusion. The stent graft composed of 30 mm Gianturco Z stent and 27.5 mm woven Dacron graft was introduced into the descending aorta under the guidance of transesophageal echocardiography (TEE) and fluoroscopy. Ascending and proximal aortic arch replacement was then performed with four branched woven Dacron graft. The aortic pathology was confirmed by TEE and the extent of the aneurysmal lesion was defined. TEE was also useful to find the dislodgement of the stent graft after deployment. This surgical technique, being less invasive than conventional thoracotomy, would be indicated for elderly patients with distal aortic arch aneurysm. TEE is the vital imaging technique for placement of the stent graft, as well as for intraoperative cardiac monitoring. PMID- 11215238 TI - [Tracheal tube damage by Harmonic Scalpel during tonsillectomy]. AB - We experienced a case in which a tracheal tube was damaged by a Harmonic Scalpel during tonsillectomy. A 33-year-old man with chronic tonsillitis underwent tonsillectomy under general anesthesia. The trachea was intubated by Polar Preformed Tracheal Tube (Polar tube). About 45 minutes after the start of surgery, sudden massive air leakage in the trachea occurred. Surgery was accomplished under oral suctioning. After extubation, we found that an inflation cuff tube was cut off by the Harmonic Scalpel. The cause of damage was the position of an inflation cuff tube which had been in the dorsal side of the tracheal tube (near the surgical field) in the Polar tube. Anesthesiologists should be aware of the characteristics of the surgical equipment newly introduced. PMID- 11215239 TI - [A case of rectal excision in a patient with cervical spinal cord injury of chronic stage]. AB - A 63-year-old man, scheduled for a Hartmann's procedure, sustained a cervical injury with resultant complete motor and sensory loss below the fourth cervical segment 39 years prior to admission. Anesthesia was induced with propofol 70 mg, vecuronium bromide 5 mg and an endotracheal tube was placed in the trachea. Anesthesia was maintained with nitrous oxide/oxygen and fentanyl. Ventilation was controlled to maintain normocapnea. We did not employ epidual anesthesia due to inability to flex the spine. We administered fentanyl to control hypertension, but it led to hypotension. And about 500 ml of bleeding also caused hypotension. These episodes of hypotension are associated with hypovolemia and instability of vascular tone. To control hypotension, we finally selected continuous intravenous administration of norepinephrine. The manifestations of cardiovascular instability during surgery in chronic stage of cervical spinal cord injury is not only hypertension associated with autonomic hyperreflexia, but also hypotension associated with instability of vascular tone and hypovolemia. PMID- 11215240 TI - [General anesthesia for a patient on hemodialysis with arteriosclerosis obliterans]. AB - A 48-year-old man with arteriosclerosis obliterans was scheduled for axillofemoral bypass. He had chronic renal failure and on hemodialysis (HD) for 22 years. On the morning of the day of surgery he received HD and two hours later anesthesia was induced with fentanyl 300 micrograms and midazolam 6 mg, and maintained with fentanyl, nitrous oxide and intermittent isoflurane. The common carotid artery was cannulated to measure arterial blood pressure because arteries in extremities were not available. Internal jugular vein at the other side of the arterial catheterization was cannulated to measure central venous pressure. Crystalloid and blood transfusion was performed to adjust hemodynamics and central venous pressure. Hemodynamics were stable during surgery and no complication occurred regarding the common carotid arterial line. The common carotid artery was useful for blood pressure monitoring in a patient whose extremities were not available. Midazolam and fentanyl could give stable hemodynamics to a patient with arteriosclerosis obliterans and chronic renal failure. PMID- 11215241 TI - [Airway obstruction after general anesthesia in a patient with the first and second branchial arch syndrome]. AB - A 20-year-old female with the first and second branchial arch syndrome underwent plastic surgery. Due to her mandibular hypoplasia and trismus, tracheal intubation was difficult even with a broncho-fiberscope. Fentanyl 100 micrograms was used for nasal intubation. Anesthesia was maintained with nitrous oxide (4 l.min-1), oxygen (2 l.min-1) and sevoflurane (0.5-3%). There were no troubles during surgery. The trachea was extubated after recovery of consciousness and spontaneous respiration. Five minutes after extubation, airway was obstructed suddenly after massive nasal bleeding. Sudden massive bleeding might have caused airway obstruction. Emergency insertion of an 18 G needle followed by Mini-trach II into the trachea through the cryothyroidal ligament improved her respiratory condition. The case suggests that preparing the instrument for the emergency cryothyroidal ligament puncture (for instance Mini-trach II) is useful for a patient with a risk of bleeding in the airway and with difficult intubation. PMID- 11215242 TI - [Perioperative management of two neonates with severe Ebstein's anomaly with pulmonary atresia]. AB - Ebstein's anomaly appearing during the neonatal period carries a high mortality rate. We report the perioperative management of two neonates with severe Ebstein's anomaly associated with pulmonary atresia. Their chest radiography revealed massive cardiomegaly, with cardiothoracic ratio of 90% and 100%, respectively. Their tracheas were intubated immediately after birth because of severe respiratory distress. The babies were laid in the prone position and one of them was managed with high frequency oscillatory ventilation (HFO) for prevention of pulmonary barotrauma and extensive atelectasis in the preoperative period. On the 4th and 3rd day after birth, respectively, they underwent Starnes procedure which consists of closure of tricuspid valve, enlargement of atrial septal defect, reduction of right atrium and creation of aortopulmonary shunt reported to be a useful palliative treatment for critically ill neonates with Ebstein's anomaly. Case 1 baby could not be weaned from cardiopulmonary bypass because of low cardiac output. Case 2 could not be weaned from extracorporeal membrane oxygenation due to hypoxia. We consider, however, treatment of respiratory failure and lung protection after birth are important for the prognosis. Perioperative use of HFO may be advantageous for the neonate with severe Ebstein's anomaly with pulmonary atresia. PMID- 11215243 TI - [Unexpected difficult intubation caused by a laryngeal web]. AB - We report a case of unexpected difficult intubation in an adult caused by a laryngeal web. A 43-year-old woman with uterine myoma was scheduled for abdominal hysterectomy. After induction of anesthesia, the vocal cords were seen clearly under laryngoscopy. Although intubation was attempted several times, a 6.5 mm internal diameter tracheal tube could not be passed below the level of the vocal cords because of resistance, and we used a laryngeal mask during anesthesia. Next morning after the operation, she developed dyspnea. Bronchoscopy revealed a very narrow airway below the level of vocal cords caused by a laryngeal web. Tracheostomy was performed. Two weeks later, tracheostomy was closed without any sequela. PMID- 11215244 TI - [A case of rhabdomyolysis after open heart surgery in a child]. AB - Rabdomyolysis usually occurs after trauma and release of myoglobin from the damaged muscle, i.e.; after ishchemic myopathy due to arterial occlusion or malignant hyperthermia. We encountered a pediatric case of rhabdomyolysis after Ross-Konnos' operation in an 8-yr-old girl with aortic regurgitation. After the first weaning from cardiopulmonary bypass (CPB), ventricular fibrillation occurred due to an insufficiency in coronary blood flow and CPB was resumed with rapid cooling of body temperature. The total CPB lasted for 5 hr 43 min. After the second weaning from CPB, myoglobinuria was found. Furthermore, blisters and abrasions appeared on her back and CPK levels were abnormally elevated (maximum 19,132 IU.l-1) without any elevation of body temperature in the postoperative course. Rhabdomyolysis due to intraoperative hypoperfusion was suspected and diuretics were administrated with a large amount of crystalloid to maintain urine output. The patient showed a good clinical course without acute renal failure. The course of this case suggests that rhabdomyolysis is one of rare complications of CPB and an early correct diagnosis of rhabdomyolysis and forced diuresis at an early stage are important to avoid acute renal failure. PMID- 11215245 TI - [New study on the history of anesthesiology--(5) and (6). Reevaluation of surgical achievements by Tokumei Takamine]. AB - A half century has passed since K. Higaon-na, a historian from Okinawa, first reported that in 1689 Tokumei Takamine (1653-1738) had performed successfully a hare-lip operation under general anesthesia with mafutsu-san for a royal grandchild Sho-eki of the Ryukyu Dynasty in the Ruykuys, now known as Okinawa. As Higaon-na obtruded his opinion above mentioned without any substantial proof on the public, and many medical historians as well as historians have followed him thereafter. No historical documents are available concerning surgical achievements by Tokumei Takamine to clarify them in detail but it clearly says in the genealogy of the Takamines that Kou Kaiyu ([symbol: see text]) taught his ancestral prescription and surgical technique of hare-lip operation to Tokumei Takamine on his repeated solicitation when they stayed in Fu-chou. Takamine made two scrolls describing the secret prescription and surgical method of hare-lip, and presented them to a magistrate Genzaimon Murao and his physician Doh-yo Isashiki in 1690. In 1986, a scroll has been found in Sendai city of Kagoshima prefecture, which was transcribed by two physicians named Antei Kore-eda and Encho Nagai at Kagoshima in 1754. No information is available about biographies of these two physicians. A careful study of this scroll has revealed that it bears the prescription of an ointment including ten remedies to dress the incision and surgical method of hare-lip. Accordingly it is clearly proven by this newly discovered scroll that Tokumei Takamine did not administer any general anesthetics when he performed surgical operations for hare-lip on several occasions. PMID- 11215246 TI - [HLA-DPB1* 0501-associated opticospinal multiple sclerosis: clinical, neuroimaging and immunogenetic studies]. PMID- 11215247 TI - [Genomic structure of the canalicular multispecific organic anion-transporter gene (MRP2/cMOAT) and mutations in the ATP-binding-cassette region in Dubin Johnson syndrome]. PMID- 11215249 TI - [Mechanism of nitric oxide production in vascular endothelium and the significance as therapeutic target--special reference to the relationship with superoxides]. PMID- 11215248 TI - [Guideline for therapy of patients with hypertension in Japan]. PMID- 11215250 TI - Advantages of high-speed simultaneous electrocardiography: re-evaluation of r waves in V1, the initial forces in V6 and abnormal Q waves. AB - The main aim of this study is to re-evaluate the r wave in V1 (rV1) and the initial forces in V6 with normal QRS duration. A total of 741 high-speed simultaneous electrocardiograms of V1 and V6 with either aVF or aVL as reference lead were recorded in patients with cardiac or noncardiac conditions. Patients with a QS pattern in V1 and/or a wide QRS complex were excluded. The peak of rV1 was beyond the nadir of the q wave in V6 (qV6) in 448 patients but coincided with the nadir of qV6 in 51 patients. The onset of the R wave in V6 (RV6) with absent qV6 was delayed in comparison with the onset of rV1 in 210 patients but coincided with the onset of rV1 in 30 patients. In this study, the nadir of a q wave either in aVL and/or aVF was never beyond the peak of an r wave in V1 except for high lateral and/or inferior infarction. In many cases rV1 appears to represent both septal activation and right ventricular activation. The absence of qV6 with some delay in the onset of RV6 in comparison with the onset of rV1 might indicate a nonpathologic absence of qV6 due to masked septal potential in the isoelectric line in V6, although the absence of qV6 with simultaneous onset of rV1 and RV6 may suggest septal abnormalities. An abnormal Q wave in aVL and/or aVF may be defined as that the nadir of q wave exceeded the peak of r wave in V1. PMID- 11215251 TI - [Current status and role of the Japanese Association of Clinical Toxicology]. AB - Since its foundation in 1983, the Japanese Association of Clinical Toxicology (JACT) has contributed greatly to the progress of intoxication medicine in Japan. It assists toxicologists and other medical experts in sharing clinical experience, including unusual intoxication cases and those found only in certain regions. As a result, toxicologists no longer must rely on intuition and personal experience. Today, the association focuses on disseminating useful intoxication information among toxicologists and the general public through the Japan Intoxication Information Center. With strong support from JACT, the center is developing a database that will provide useful information to physicians who need to identify poisonous chemicals quickly in their toxic patients. It is also building a system for registering intoxication treatment experts which will be publicly accessible, and an Internet Web site to provide intoxication-related information online. JACT itself is also preparing to establish the Japan Intoxication Analysis Center. JACT is committed to improving intoxication medicine in Japan by continuing to help train toxicologists and the medical specialists who support them, making useful information readily available to them, and assisting them to identify toxic materials. PMID- 11215252 TI - [Current activities of the Japan Poison Information Center and Information Network for Poisoning via the Internet]. AB - The current activities of the Japan Poison Information Center and poison information originally collected by it are explained. The Information Network for Poisoning via the Internet in Japan is also introduced, including some useful related sites based abroad. PMID- 11215253 TI - [Role of level-1 trauma and critical care centers in treatment of acute poisoning]. AB - In the summer of 1998, the so-called Wakayama currty poisoning case occurred, and subsequently additional murders took place in which the accusred used sodium aziede and thallium to posison their victims. When the poison victims were admitted to hospital, food poisoning was mistakenly diagnosed. Due to serious concerns that such misdiagnoses might recur, the Japanese Ministry of Health and Welfare equipped 10 level-1 trauma and critical care centers and 66 critical care centers nationwide with high-performance liquid chromotographs, ion chromatographs, gas chromatographs, fluorescence X-ray analyzers, and high frequency plasma mass spectrometers. This equipment will allow the detection of most types of industial and other chemicals as well as most therapeutic drugs. This report describes the current status of poison analysis systems and the role of level-1 trauma and critical care centers in cases of poisoning. PMID- 11215254 TI - [Toxicologic screening in Japan]. AB - What we have learned from the Tokyo subway sarin gas attack on March 20, 1995, and the Wakayama poisoned curry incident on July 25, 1998, is that Japanese system for the analysis of drugs and poisons for medical treatment is extremely poor. The frequent occurrence of crimes involving drugs and poisons has become a serious problem. In response, the government established the Countermeasure Committee for Poisonous and Dangerous Substances, which submitted a report in November 1998. Based on that report, the Ministry of Health and Welfare equipped emergency medical centers with expensive analytical instruments, such as high performance liquid chromatography columns and fluorescence X-ray analyzers, upon request. However, problems in their operation have occurred, and few such facilities work efficiently. In the Wakayama incident, the initial was food poisoning. Only after 11 hours and the deaths of four people was the diagnosis of cyanide poisoning made public. During that process, at least three mistakes were made. We believe that a basic and correct understanding of those mistakes and the development of countermeasures are necessary to analyze drugs and poisons from a medical standpoint. PMID- 11215255 TI - [Diagnosis of acute poisoning]. AB - The discrimination of poisoning from other conditions is essential. When multiple patients with similar clinical findings are seen, deliberate poisoning should be considered along with the possibility of resulting from accidental food poisoning, infection, diseases resulting from extreme circumstances, and mass hysteria. The diagnosis of causal poisoning chemicals based on clinical findings is essential. Breath odors, findings of vomitus, skin color, body temperature, autonomic nervous system findings, and seizures are important physical findings. On the other hand, laboratory findings such as ECG abnormalities, metabolic acidosis, increased serum hepatic enzyme levels, and increased serum blood urea nitrogen and creatinine levels are also useful in obtaining the correct diagnosis. X-ray films are useful in demonstrating several types of radiopaque drugs in the stomach. Rapid tests are valuable in diagnosing poisoning caused by such chemicals as paraquat and cyanides. Therapeutic diagnoses obtained by administering competitive blockers of specific receptors are also valuable when benzodiazepine or opiate poisoning is suspected. The final diagnosis of the causal chemical should be based on both the clinical findings and analytical results. PMID- 11215256 TI - [Poison elimination methods in acute poisoning]. AB - This paper presents current ideas about the application of poison elimination methods in acute poisoning. The methods are divided into two groups: poison elimination before absorption; and enhancement of elimination after drug absorption. The former include washes, emesis, gastric lavage, and administration of activated charcoal and cathartics, while the latter include forced diuresis and extracorporeal toxin elimination such as hemodialysis or hemoperfusion. The indications, contraindications, techniques, and complications, associated with these elimination methods, except for extracorporeal toxin elimination, are discussed. In the treatment of poisoning, early and comprehensive poison elimination is important. PMID- 11215257 TI - [Blood purification in toxicology]. AB - Although toxic substances can be removed by blood purification techniques such as hemodialysis and hemoperfusion, the complete elimination of toxic substances from the whole body is difficult even if clearance values are high. Blood purification over in a limited time sometimes cannot prevent the death of patients, because the volume of distribution of toxic substances is usually very high. It should also be stressed that initial general management of patients is very important whenever blood purification procedures are utilized. PMID- 11215258 TI - [Antidotes for poisoning and medication overdosage]. AB - Supportive therapy is crucial in the treatment of severe intoxication. Furthermore, specific antidotes are available to neutralize or prevent the toxic effects of poisoning and overdosage. Recently it has become possible to determine the probable toxicity precisely by plotting plasma poison or drug levels. This is especially appropriate in severely intoxicated patients. We conclude that the screening of blood using special agents is the most important in the treatment of such patients at present. PMID- 11215259 TI - [Mass-casualties due to chemicals]. AB - Mass casualties due to chemicals and chemical weapons are typical man-made disasters. As they occur without connection to time, place, and occasion, an adequate crisis control system is needed. Although the possibility that chemical weapons will be used in terrorism, as in Matsumoto and the Tokyo sarin attack, has recently increased, mass casualities due to the combustion and leakage of toxic chemicals in the chemical industry and traffic accidents during the transport of chemicals are more likely since about 5000 new chemical substances are synthesized every year. PMID- 11215260 TI - [Continuous monitoring of hepatic venous oxygen saturation (SHVO2) as a new diagnostic indicator of abdominal malperfusion in acute aortic dissection]. AB - A 73-year-old woman was admitted with sudden-onset back and abdominal pain. Computed tomography scanning revealed type B acute aortic dissection with narrowing of the true lumen. We inserted an oximetric catheter into the right hepatic vein and started continuous measurement of ShvO2. The initial value was 20%. Consecutive aortograms showed an intimal tear in the thoracic descending aorta. Endovascular stent graft placement was performed to close the entry, and ShvO2 rose to more than 60% immediately after the stent graft expansion. ShvO2 is an excellent indicator of abdominal blood flow, not only for early diagnosis but also for the evaluation of treatment. PMID- 11215261 TI - [A surgical case of abdominal aortic aneurysm accompanied by hamartomatous changes in the vascular wall]. AB - The current patient was a 22-year-old woman with dyspnea on exertion that had exacerbated over the past two to three years. Chest X-ray indicated pneumothorax in the right lung, and chest computed tomography showed diffuse microcysts in both lungs. The patient was diagnosed with lymphangiomyomatosis based on pleural biopsy by intrathoracic endoscopy. Systemic testing revealed complications of tuberous sclerosis and abdominal aortic aneyrysm, and a prosthetic graft replacement was perfomed following pneumothorax treatment. Aortic wall tissue images showed hamartomatous changes in smooth muscle tissue, similar to the pulmonary lesion, and this was thought to have caused vascular fragility and aneurysmal change. PMID- 11215262 TI - [A case of acute type adult T cell leukemia and human T-lymphotropic virus type I associated myelopathy who presented meningitis and polyradiculoneuropathy and improved with steroid treatment]. AB - We reported a 35-year-old male patient with acute type adult T cell leukemia(ATL) and human T-lymphotropic virus type I associated myelopathy. He presented meningitis and polyradiculoneuropathy and improved with steroid treatment. He presented headache and sensory ataxia and these symptoms responded to steroid treatment. The usual clinical features of ATL were absent at onset. There existed ATL-like cells in the cerebrospinal fluid and HTLV-I proviral DNA in the blood. Therefore, we surmised that there was monoclonal hyperplasia of the infected cells. He presented ATL after 2 years remission. We pointed out that there was acute type of ATL in patients with meningitis and polyradiculoneuropathy, for which steroid treatment could be effective. PMID- 11215264 TI - [Two cases of cranial pachymeningitis presenting only severe continuous headache or convulsion]. AB - In cranial pachymeningitis, headache, cranial nerve palsies, and ataxia were the most common clinical manifestations. We reported two rare cases presenting only headache or convulsion as a main symptom. A 66-year-old man was suffering from severe continuous headache for years with no other clinical symptoms. Laboratory data revealed positive RA test and elevated RAPA. With oral steroid therapy, his headache was subsided. A 39-year-old woman visited us with convulsive attacks as only symptom. Biopsy of the thickened dura revealed granulated epithelioid cells without central necrosis. With antituberculosis therapy, hypertrophy of dura, as well as the symptom, was disappeared. It is difficult to diagnose pachymeningitis when patients manifest only headache or convulsion. We suggest to carry out Gd enhanced MR scan in these cases. PMID- 11215263 TI - [A case of antiphospholipid antibody syndrome with cerebral infarction showing slowly progressive pure motor monoparesis in unilateral upper extremity]. AB - We reported a 68-year-old man with anti-phospholipid antibody syndrome who presented slowly progressive pure motor monoparesis(PMM) in left upper extremity as a sign of cerebral infarction. He had history of hypertension and hyperlipidemia. He first noticed clumsiness in left fingers, then weakness of left fingers with drop hand developing gradually in 2 to 6 weeks. He began to feel difficulty in raising left upper arm in 8 weeks and was admitted to our hospital. On admission, he exhibited severe weakness in distal portion and moderate weakness in proximal portion of left upper extremity. Deep tendon reflexes were slightly hyperactive in left side. Muscle strength of right upper extremity and bilateral lower extremities were normal. There was no sensory and autonomic abnormality. Laboratory examination revealed high titer of anti cardiolipin IgM antibody. Brain MRI demonstrated a small cortical infarction in the right precentral gyrus. Cerebral angiography revealed severe stenosis in right common carotid artery. Other examinations including EMG were unremarkable. PMM in left upper extremity was considered to be caused by the ischemic lesion in the precentral motor cortex. Slowly progressive course might be explained by the hypovolemic factor due to the marked stenosis in right common carotid artery, poor collateral circulation, and abnormal coagulation caused by anti-phospholipid antibody syndrome. PMID- 11215266 TI - [A case of bitemporal epilepsy that was well controlled after unilateral lobectomy]. AB - Here we report a case of bitemporal epilepsy that was well controlled after unilateral temporal lobectomy. The patient was a 31-year-old woman, who was born in an asphyxia state and had a history of a febrile convulsion. Complex partial seizure(CPS) preceded by abdominal aura appeared at the age of three. Despite anticonvulsant medication, the seizures gradually increased in frequency and sometimes developed into secondary generalized convulsions. Her scalp electroencephalogram(EEG) showed interictal spikes and seizure activities arising from the bilateral temporal lobes. No apparent lateralities in regard to the size or blood flow at the hippocampus were detected by MRI and SPECT studies. Intracranial EEG monitoring revealed that 80% of the clinical seizures originated from the left mesial temporal lobe, which was the non-dominant side for speech and memory functions as demonstrated by Wada test. Therefore, we performed a left temporal lobectomy that resulted in the complete disappearance of CPS. The present case exemplified the usefulness of intracranial EEG monitoring to clarify the dominant epileptic focus for surgery. PMID- 11215265 TI - [Relationship between cardiac natriuretic peptide (ANP/BNP) and fluid intake in patients with subarachnoid hemorrhage]. AB - Several authors described elevated natriuretic peptides, atrial natriuretic peptide(ANP) and brain natriuretic peptide (BNP), in patients with subarachnoid hemorrhage(SAH), which were account for inappropriate antidiuretic hormone(SIADH) or cerebral salt wasting syndrome(CSW). Although the secretion of natriuretic peptide depends on the total blood volume, central venous pressure, and cardiac output volume, the volume of fluid intake in patients with SAH had not been taken in consideration in previous report. We here examined the relationship between fluid intake and the natriuretic peptides in two cases without cardiac failure. ANP elevated 2 or 3 days after SAH and remained in normal range for 2 weeks. BNP elevated when the volume of fluid intake was increased, and BNP did not elevate during the periods with lower fluid intake. Several authors proposed the possibility of iatrogenic factor in natriuresis after SAH and these results supported this opinion. PMID- 11215267 TI - [Serial MRI of tuberculous meningitis]. PMID- 11215268 TI - [Surgical therapy for Parkinson's disease]. PMID- 11215269 TI - [Atopic myelitis and related disorders]. PMID- 11215270 TI - [Isolated extensor digitorum brevis involvement in the population of normal systemic nerve conduction velocities]. AB - To investigate the characteristics of isolated atrophy in extensor digitorum brevis(EDB), we analysed 262 patients whose polyneuropathy index(PNI) was 90% or more than the normal mean value. The PNI was determined as the mean percentage of the normal in 12 indices concerning to the velocity or long distance latency in motor nerve conduction studies. Latencies were adjusted to 160 cm height. Amplitude of compound muscle action potential (CMAP) in EDB showed no correlation with the patient's age. Similar result was obtained as well when studied in 115 patients whose PNI level was 95% or more than the mean normal value. In 18(7%) out of 262 patients CMAP amplitude in EDB was 1 mV or less; larger prevalence(p < 0.05) in women(10%) than in men(4%). The number of motor units which innervate EDB decreases along with the age, but this age-related change could be compensated by the magnification of each motor unit. In Western reports isolated EDB palsy has a predilection for emaciated men. Instead, our results showed the predominance in women. We may have some factors other than in Western countries, for example customs to sit directly on the mat for a long time, in the occurrence of isolated EDB palsy. In conclusion, amplitude reduction in EDB CMAP may reflect the following two factors; neuropathy-related factor and another factor independent of age or neuropathy. PMID- 11215271 TI - [A study of reduction of NF 2 protein, mRNA and loss of 22 q in sporadic meningiomas]. AB - Neurofibromatosis 2(NF 2) is one of the tumor suppressor genes, and its disorder has been reported in sporadic meningiomas. We investigated some reduction of expression of NF 2 protein and mRNA in 33 sporadic meningiomas, using immunohistochemistry and in situ hybridization, respectively. Seventeen of 33 (51.5%) meningiomas demonstrated significantly reduced or absent NF 2 protein expression. Its mRNA was also reduced or absent in 11 of 24(45.8%) meningiomas, and some statistically significant correlation was shown between reductions of NF 2 protein and its mRNA. Furthermore, we studied about loss of 22 q in 5 meningiomas with fluorescence in situ hybridization. In the cases with reduction of NF 2 protein and/or mRNA, 22 q telomere signals were observed as loss of heterozygosity. On the other hand, in the cases with expression of NF 2 protein and mRNA, 22 q telomere signals were normal. In conclusion, reduction or absence of NF 2 protein and mRNA may play an important role in the tumorigenesis of about half number of sporadic meningiomas. PMID- 11215272 TI - [Amnesia following herpes simplex encephalitis]. AB - We describe three patients presenting themselves with amnesia following herpes simplex encephalitis. All three patients showed anterograde amnesia. Moreover, one patient showed retrograde amnesia extending about fifty years prior to the onset of the illness. Two patients revealed semantic memory disorder, disinhibitory behaviors and confabulations, which suggested the existence of frontal lobe dysfunction. MRI of all three patients disclosed uni- or bilateral temporal lesions. SPECT images showed decreased uptake not only in the temporal lobes but also in the frontal lobes. Amnesia following herpes simplex encephalitis has been thought to be caused by the temporal lobe disorder. However, we postulate that the frontal lobe dysfunction might contribute to the appearance of amnesia. PMID- 11215273 TI - [An analysis of characters and changes of the blood pressure in 29 cases on recurrence of cerebral infarction]. AB - We investigated changes of the blood pressure in 29 stroke patients before stroke recurrence and after recurrence. Additional antihypertensive drugs were not administered to all patients after stroke recurrence. Twenty-five lacunar infarct patients and 4 atherothrombotic infarct patients were included in this study. A significant difference was observed between the systolic blood pressure(SBP) within 4 weeks before recurrence and that just after recurrence(132.8 +/- 17.2 mmHg vs. 157.4 +/- 21.3 mmHg, Wilcoxon rank sum test, p < 0.001), or between the SBP just after and 2 weeks after stroke recurrence(157.4 +/- 21.3 mmHg vs. 138.0 +/- 18.3 mmHg, Wilcoxon rank sum test, p < 0.001). The similar difference was found in the diastolic blood pressure(DBP) or in the mean arterial blood pressure(MABP). There was no significant difference in the SBP, the DBP or the MABP between the patients before and 2 weeks after the stroke recurrence. These results suggested that the elevation of the blood pressure at recurrence decreased spontaneously to the pre-recurrence level of the blood pressure in about 2 weeks. PMID- 11215274 TI - [rCBF study with 123I-IMP SPECT of dural arteriovenous fistula]. AB - It is important for dural arteriovenous fistula (DAVF) to evaluate venous ischemia in the brain related to venous hypertension, but only a few such studies have been performed. In this study, regional cerebral blood flow(rCBF) in DAVF was examined for venous ischemia by 123I-IMP SPECT. The subjects were eighteen patients with DAVF. Of the eighteen patients, nine had DAVF with low perfusion areas and venous ischemia. The factors affecting rCBF in DAVF are: 1) the presence of retrograde leptomeningeal venous drainage, 2) sinus occlusion, and 3) DAVF with high flow. The presence of retrograde leptomeningeal venous drainage was observed in nine patients, sinus occlusion in four patients, high flow in three patients. In two patients, pure leptomeningeal venous drainage was formed by patent sinus, and blood regurgitated from DAVF on the sinus wall to cortical vein. When DAVF was associated with LMVD, most patients had venous hypertension and concomitant venous congestion in the same areas due to reduced venous circulation, resulting in a decrease in rCBF and an increase in regional cerebral blood volume. These hemodynamics suggest venous ischemia in the brain. 123I-IMP SPECT was useful for evaluating rCBF and as a parameter of the treatment. PMID- 11215275 TI - [A case of tentorial meningioma presented with pure word deafness]. AB - It has been known that an isolation of Wernicke's area from auditory input results in pure word deafness. In this report, a 73-year-old female case with tentorial meningioma suffering from pure word deafness is reported. The patient initially presented with hydrocephalus, and was treated with a ventriculo peritoneal(V-P) shunt. A year after the V-P shunt, she suffered from a symptom of deafness. On admission, her repetition and auditory comprehension were severely impaired, while reading and visual comprehension were almost normal. Auditory brain stem response(ABR) revealed normal latency between wave I and V, while wave VI and VII was disappeared. Middle latency response(MLR) showed no wave peak. On MRI, tentorial meningioma compressed bilateral medial geniculate bodies, but not auditory radiation or temporal lobe. 99mTc-HMPAO single photon emission computed tomography(SPECT) showed hypoperfusion in the left temporal lobe, considered as a diaschisis resulting from the isolation of left temporal lobe from auditory input via bilateral medial geniculate bodies. PMID- 11215277 TI - Diagnosis of gram negative, ventilator associated pneumonia by assaying endotoxin in bronchial lavage fluid. AB - AIM: To investigate the usefulness of assaying endotoxin in non-directed bronchial lavage fluid (NBL), bronchoscopic bronchoalveolar lavage fluid (BAL), and sera as a means of diagnosing Gram negative, ventilator associated pneumonia. METHODS: Samples from 64 patients were investigated. Fifty nine BALs and 92 NBLs were assayed in total including specimens taken during 28 episodes of clinical ventilator associated pneumonia (VAP). RESULTS: The concentration of endotoxin in BAL from patients with VAP developing within four days of commencing ventilation was significantly higher than in those without VAP (p = 0.015). There was no significant difference in endotoxin concentration in NBL or serum when comparing patients with and without VAP. A BAL endotoxin concentration of 6 EU/ml yielded the optimal operating characteristics (sensitivity, 81%; specificity, 87%; positive predictive value, 67%; negative predictive value, 95%). However, Gram stain of BAL provided the same information as quickly as the endotoxin assay and is considerably cheaper. CONCLUSIONS: Despite its accuracy and rapidity, the BAL endotoxin assay must be shown to alter clinical management and patient outcome to be cost effective. PMID- 11215276 TI - Detection of herpesvirus DNA by the polymerase chain reaction (PCR) in vitreous samples from patients with necrotising retinitis. AB - AIMS: Viral uveitis and retinitis, usually caused by herpesviruses, are common in immunosuppressed patients. The diagnosis of viral anterior uveitis and retinitis is usually clinical. The polymerase chain reaction (PCR) has been used for the diagnosis of some viral infections, especially those caused by herpesviruses. This paper reports the use of PCR in the diagnosis of viral retinitis in vitreous samples from Brazilian patients. METHODS: PCR was used for the diagnosis of necrotising retinitis in vitreous samples from patients from the Hospital Sao Geraldo, Universidade Federal de Minas Gerais, Brazil. The vitreous samples were collected by paracentesis and stored until analysis. Samples were analysed by PCR using specific primers designed to amplify herpes simplex virus 1 (HSV-1), varicella zoster virus (VZV), or human cytomegalovirus (HCMV). In a case of anterior uveitis, PCR was performed with a sample from the anterior chamber. RESULTS: Herpesvirus DNA was amplified in 11 of 17 samples. HCVM DNA was detected in nine samples but DNA from HSV-1 and VZV were detected only once each. CONCLUSION: These results strongly suggest that PCR could be used for a rapid complementary diagnosis of viral uveitis and retinitis. A prospective study to evaluate the PCR results, clinical evolution, and treatment is imperative to corroborate the real value of PCR in diagnosis and how it could help the clinicians' approach. PMID- 11215278 TI - Apoptosis in squamous cell carcinoma of the lung: correlation with survival and clinicopathological features. AB - AIMS: Apoptosis is recognised as a physiological mechanism for controlling cell numbers and its subversion is thought to contribute to carcinogenesis. The aims of this study were to measure the apoptotic index (AI) in a series of squamous cell carcinomas (SCCs) of the lung using standard histological staining and confirm this by immunohistology using an antibody to an apoptosis specific protein (ASP), and to seek to correlate the AI with clinicopathological parameters. METHODS: Sections of 134 SCCs were stained by haematoxylin and eosin (H&E) for counting apoptotic bodies of determine the AI (number of apoptotic bodies/10,000 tumour cells); 26 of these were also stained with anti-ASP antibody and the proportion of ASP positive cells counted. Clinical data were obtained from hospital notes. RESULTS: The mean AI obtained by H&E staining of all 134 SCCs was 30.3 (SD, 24.75). Anti-ASP staining allowed easy identification of apoptotic bodies, and generated a somewhat higher index (mean, 51.4; SD 39); this was not a result of the selection of tumours because the AI by H&E in the subset stained with anti-ASP was 31.1. Regression analysis showed that the correlation between the two values of AI was highly significant (Rs = 0.9760; p < 0.001), indicating that the two methods were both reliable measures of apoptosis but that the anti-ASP staining is the more sensitive method. The tumours were grouped into high AI (> 50) and low AI (< 50) and survival analysis was carried out. The mean survival of the high AI group was 109 weeks and of the low AI group 72 weeks (p = 0.036). CONCLUSIONS: Anti-ASP staining is a reliable, easy, and sensitive method for assessing apoptosis in tumour sections and confirms the validity of the AI obtained by H&E staining. AI is a guide to the behaviour of SCCs of the lung. PMID- 11215279 TI - Prognostic value of vascularity and vascular endothelial growth factor expression in non-small cell lung cancer. AB - AIMS: High expression of the angiogenic factor vascular endothelial growth factor (VEGF) in tumours has been found to be associated with poor prognosis in some studies, but not in others. The aims of this study were to determine the prognostic value of VEGF in operable non-small cell lung cancer (NSCLC) and its possible association with vascularity. METHODS: Sections from 81 NSCLC archival specimens were stained with antibodies to von Willebrand factor (vWF) and VEGF. Vascularity was measured by the average density of vWF positive vessels. VEGF expression in tumour cells was assessed by consensus of two independent observers according to three indices, namely: (1) percentage of area stained, (2) intensity of staining, and (3) final score (product of area and intensity). RESULTS: VEGF immunoreactivity was present in all tumours and adjacent normal lung tissue. None of the three VEGF indices was associated with vascularity or the clinical parameters examined. Mean survival times were shorter in patients with high VEGF expression, but the difference was not significant. This applied to the full cohort of patients, or when analysed separately according to tumour type or stage. However, high VEGF expression was associated with poor survival in patients with high vascularity (p = 0.02). VEGF had no discriminant value among patients with low vascularity. Vascularity had no prognostic value, except for late stage patients (UICC stages II and IIIa combined; n = 36), where high vascularity was associated with longer survival (p = 0.01). CONCLUSIONS: VEGF on its own has no prognostic value in NSCLC, but may become a useful indicator when combined with vascularity. VEGF may play a physiological role in the normal lung. PMID- 11215280 TI - The role and histological classification of needle core biopsy in comparison with fine needle aspiration cytology in the preoperative assessment of impalpable breast lesions. AB - AIMS: To investigate the role of needle core biopsy (NCB) in the preoperative assessment of impalpable breast lesions, mainly derived from the NHS Breast Screening Programme (NHSBSP) and to assess our own modifications to a suggested system for the classification of breast NCBs. METHODS: The NCB, fine needle aspiration cytology (FNAC), and radiology scores from 298 women with non-palpable breast lesions presenting between January 1997 and December 1998, together with the open biopsy results (where available) were collated and analysed. RESULTS: The mean follow up period was 15.8 months (range, 5-28). The 298 NCB specimens were categorised as follows: unsatisfactory/non-representative (B1; n = 61; 20.5%), benign but uncertain whether representative (B2r; n = 52; 17.4%), benign (B2; n = 103; 34.6%), lesions possibly associated with malignancy but essentially benign (B3a; n = 9; 3.0%), atypical epithelial proliferations (B3b; n = 10; 3.4%), suspicious of malignancy (B4; n = 7; 2.3%), and malignant (B5; n = 56; 18.7%). Excision biopsy was performed in 43 cases within the B1 (n = 19), B2r (n = 8), B2 (n = 8), and the B3a (n = 8; data unavailable in one case) categories, revealing malignancy in 18 (42.8%) cases and in 65 cases within the B3b, B4, and B5 categories, revealing malignancy in 64 cases (98.5%). The sensitivity of NCB for malignancy was 87.7%, with a specificity and positive predictive value of 99.3% and 98.5%, respectively. FNAC had an inadequacy rate of 58.7%, a complete sensitivity of 34.5% and a specificity of 47.6%. CONCLUSIONS: This study confirms the value of NCB in the preoperative assessment of impalpable breast lesions. Two new categories are suggested for the NCB classification; category B2r for benign breast tissue where representativeness is uncertain, and the subdivision of category B3 into B3a for benign lesions potentially associated with malignancy (for example, radial scars and intraduct papillomas) and B3b for more worrisome atypical epithelial proliferations. These will aid the accurate audit of NCB and identify more clearly the intellectual pathway leading to a particular assessment. PMID- 11215281 TI - Molecular genetic alterations in hamartomatous polyps and carcinomas of patients with Peutz-Jeghers syndrome. AB - AIM: To investigate whether mutations in the STK11/LKB1 gene and genes implicated in the colorectal adenoma-carcinoma sequence are involved in Peutz-Jeghers syndrome (PJS) related tumorigenesis. METHODS: Thirty nine polyps and five carcinomas from 17 patients (from 13 families) with PJS were analysed for loss of heterozygosity (LOH) at 19p13.3 (STK11/LKB1 gene locus), 5q21 (APC gene locus), 18q21-22 (Smad4 and Smad2 gene locus), and 17p13 (p53 gene locus), and evaluated for immunohistochemical staining of p53. In addition, mutational analysis of K ras codon 12, APC, and p53 and immunohistochemistry for Smad4 expression were performed on all carcinomas. RESULTS: LOH at 19p was seen in 15 of the 39 polyps and in all carcinomas (n = 5). Interestingly, six of the seven polyps from patients with cancer had LOH, compared with nine of the 31 polyps from the remaining patients (p = 0.01). In one polyp from a patient without a germline STK11/LKB1 mutation, no LOH at 19p or at three alternative PJS candidate loci (19q, 6p, and 6q) was found. No LOH at 5q was observed. However, mutational analysis revealed an APC mutation in four of the five carcinomas. LOH at 17p was not seen in polyps or carcinomas; immunohistochemistry showed expression of p53 in one carcinoma and focal expression in three polyps. At subsequent sequence analysis, no p53 mutation was found. One carcinoma had an activating K-ras codon 12 mutation and another carcinoma showed 18q LOH; however, no loss of Smad4 expression was seen. CONCLUSIONS: These results provide further evidence that STK11/LKB1 acts as a tumour suppressor gene, and may be involved in the early stages of PJS tumorigenesis. Further research is needed to see whether LOH in PJS polyps could be used as a biomarker to predict cancer. Differences in molecular genetic alterations noted between the adenoma-carcinoma sequence and PJS related tumours suggest the presence of a distinct pathway of carcinogenesis. PMID- 11215282 TI - Evidence of type II pneumocyte apoptosis in the pathogenesis of idiopathic pulmonary fibrosis (IFP)/usual interstitial pneumonia (UIP). AB - BACKGROUND/AIMS: The pathogenesis of idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP), a chronic and incurable human respiratory disease, is not well established. This study was designed to investigate whether the apoptosis of type II pneumocytes could be the precipitating factor in the pathogenesis of IPF. METHODS: Nineteen specimens obtained by retrospective review of the medical and pathological records of 55 patients with IPF, four normal subjects, and 10 disease control lungs were analysed. The selected specimens had normal alveoli with intervening patchy scarring of the lung parenchyma, fulfilling the pathological criteria for UIP. To identify individual cells undergoing apoptosis in the normal alveoli, electron microscopy and in situ end labelling of fragmented DNA were performed on paraffin was embedded sections using digoxigenin-11-dUTP and the enzyme terminal deoxynucleotidyl transferase. RESULTS: Apoptosis was detected in the normal alveoli of 17 of the 19 patients with IPF/UIP and was absent in the controls. Electron microscopy demonstrated apoptotic changes in type II pneumocytes. These results indicate that apoptotic type II pneumocyte death occurs in normal alveoli of IPF/UIP and could be the principal cause of several events that account for the histological, clinical, and functional alterations seen in IPF/UIP. CONCLUSIONS: In conclusion, numerous type II pneumocytes from the normal alveoli of most patients with IPF/UIP actively undergo programmed cell death. This finding may shed new light on the pathogenesis of this disease, with implications mainly for the treatment of affected patients. PMID- 11215283 TI - Age related changes in the tunica media of the vertebral artery: implications for the assessment of vessels injured by trauma. AB - AIMS: To provide an illustrated, detailed semiquantitative analysis of the important degenerative changes along the length of the vertebral artery so that pathologists faced with investigating a fatal arterial injury can identify important pre-existing wall abnormalities. METHODS: Ten transverse annuli were taken along 34 vertebral arteries from 17 subjects and stained sections were prepared using haematoxylin and eosin and the picro-sirius red method. After routine microscopy, the elastic fibres, collagen, and smooth muscle nuclei in the tunica media were quantified using an eyepiece graticule. An estimate of the severity and extent of elastic tissue fragmentation, collagenous scarring, and intimal thickening/atheroma was then undertaken. RESULTS: Smooth muscle counts remained constant along the artery but collagen counts were higher and elastic counts substantially lower within the intracranial segment. Elastic fibre fragmentation was recognised in infancy and was moderately advanced by early adulthood but considerable collagenous scarring developed later in life. Some individuals demonstrated severe fragmentation and scarring before the age of 35 years. The degenerative changes were often focal and spared the intracranial segment almost completely. Atheroma increased with age but was rarely severe and appeared not to worsen appreciably beyond the age of 40 years. An unusual arrangement of the collagenous tissue was described within the upper cervical loops. CONCLUSION: Damaged vertebral arteries need to be sampled extensively to allow a proper histological assessment. The picro-sirius red method was successful in delineating the fine connective tissue structure of the wall and early degenerative changes. An understanding of the age and site specific changes should allow the pathologist to recognise important pre-existing abnormalities more easily. PMID- 11215284 TI - The importance of intracytoplasmic DPAS positivity in fine needle aspirates of breast lesions. AB - AIMS: For many years the presence of strong intracytoplasmic periodic acid Schiff (PAS) positive, diastase resistant (DPAS) staining within atypical cells has been used in this laboratory as a marker for carcinoma in fine needle aspirates from breast lesions. The aim of the current study was to document such DPAS positivity across the spectrum from benign to malignant breast disease and assess its value in the upgrading of cytology reports. METHODS: Over a six month period, 315 aspirates were studied, each having sufficient cellular material for DPAS staining to be carried out on one whole slide. DPAS staining was recorded semiquantitatively as negative, equivocal, or positive (+, ++, or +++). The cytology results were correlated with any subsequent histology performed on these patients. RESULTS: DPAS positive material was seen in both intracellular and extracellular locations. Care was needed in its interpretation. Occasional cells with apparently genuine intracytoplasmic positivity (+) were found in both benign and malignant cases. Frequent or particularly strong intracellular DPAS positivity (++, +++) correlated best with malignancy. Two cases were reliably upgraded from immediate reports suspicious of malignancy to final reports diagnostic of malignancy on the basis of the intracytoplasmic DPAS staining. CONCLUSION: Strict criteria are required for the interpretation of intracytoplasmic DPAS positivity and routine cytological appearances should also be taken into account. Weak positivity in occasional cells, especially in flat epithelial sheets, may be seen in benign lesions and is not reliable as a marker of malignancy. DPAS positivity with internal structure and producing nuclear indentation, especially in dissociated or atypical cells, correlates well with malignant histology and can be reassuring in the cytological diagnosis of malignancy. PMID- 11215285 TI - Anaplastic large cell lymphoma with the t(2;5)(p23;q35) NPM/ALK chromosomal translocation and duplication of the short arm of the non-translocated chromosome 2 involving the full length of the ALK gene. AB - This report describes a case of anaplastic large cell lymphoma with the canonical t(2;5)(p23;q35) translocation in association with duplication of the short arm of the non-translocated chromosome 2, as demonstrated by two colour fluorescence in situ hybridisation. Because the tumour cells were tetraploid, these abnormalities were in duplicate, with four copies of the full length ALK gene and two copies of the t(2;5)(p23;q35) translocation. Despite multiple copies of the normal ALK gene, immunohistochemical, reverse transcriptase polymerase chain reaction, and western blot analysis demonstrated that only the fusion gene NPM/ALK was expressed and that normal ALK genes remained silent. Although based on a single case, these data indicate that structural rather than numerical abnormalities of the ALK gene are implicated in the pathogenesis of anaplastic large cell lymphomas. PMID- 11215286 TI - The appropriateness of examining the entire cervix histologically in hysterectomy specimens from women with a previous history of cervical intraepithelial neoplasia or dyskaryosis. AB - BACKGROUND/AIMS: To investigate the necessity of examining the entire cervix in hysterectomy specimens from women with a previous history of cervical intraepithelial neoplasia (CIN) or dyskaryosis. METHODS: The overall frequency with which squamous CIN was encountered in hysterectomy specimens of women with a previous diagnosis of squamous CIN or dyskaryosis was calculated in a sample of 71 women. The frequencies in women with positive or negative smears or biopsies between the initial diagnosis and hysterectomy, and in women with no intervening smear or biopsy, were also estimated. RESULTS: A persistent CIN lesion was identified in 18 patients (13 high grade cases; five low grade cases). A further eight patients who had high grade CIN also had microinvasive disease (seven cases of FIGO stage 1a1; one case of FIGO stage 1a2). Ten of the 20 patients with a positive smear or biopsy, but none of the 16 patients with a negative smear or biopsy between initial diagnosis and hysterectomy, had an abnormality on the hysterectomy specimen. Sixteen of the 35 patients who did not have an interim smear or biopsy had CIN in the hysterectomy cervix. CONCLUSIONS: These results support continuing the practice of examining the entire cervix in hysterectomy specimens from women with a previous cervical abnormality, regardless of its histological or cytological grade, if there has been a positive interim smear or biopsy or if neither investigation has been performed. PMID- 11215288 TI - The use of the Reflection computer program for facilitating report formulation in the medical microbiology laboratory. PMID- 11215287 TI - Evaluation of CHROMagar candida for rapid identification and Etest for antifungal susceptibility testing in a district general hospital laboratory. PMID- 11215289 TI - Immunology of chronic mucocutaneous candidiasis. PMID- 11215290 TI - Investigation of CMV disease in immunocompromised patients. AB - Cytomegalovirus (CMV) is a recognised cause of morbidity and mortality in immunocompromised individuals. This review will concentrate on recent advances in the understanding of the complex interplay between the host and parasite and the pathological consequences of perturbation of the host immune system. The classic view of CMV as a slowly replicating virus is challenged by recent in vivo findings suggesting that active replication occurs dynamically in the human host, with a doubling time of approximately one day. In addition, CMV load plays a major role in viral pathogenesis, such that increased CMV replication is a significant risk factor for disease in all immunocompromised groups studied to date. These studies focus attention on understanding the virological and immunological determinants of enhanced viral replication and its pathological consequences. PMID- 11215291 TI - Laboratory testing under managed care dominance in the USA. AB - The uncontrolled escalation of total health care expenditure despite the government's endeavours during the past decades in the USA had led to the rapid infiltration of managed care organisations (MCOs). Traditional hospital based laboratories have been placed in a crucial situation with the advent of the managed care era. A massive reduction of in house testing urged them to develop strategies against financial difficulty. Consolidation and networking, participation in the outreach testing market, and emphasis on point of care/satellite laboratory testing in non-traditional, ambulatory settings are major strategies for the survival of hospital laboratories. Several physicians' office laboratories (POLS) have closed their doors in response both to regulatory restrictions imposed by the Clinical Laboratory Improvement Amendments of 1988 and to managed care infiltration. It seems likely that POLs and hospital laboratories will continue to reduce test volumes, whereas commercial reference laboratories will thrive through contracting with MCOs. In the current climate of managed care dominance in the USA, clinical laboratories are changing their basic operation focus and mission in response to the aggressively changing landscape. PMID- 11215293 TI - The use of material from the dead in forensic science research: is it lawful and is it ethical? PMID- 11215292 TI - The histopathological differential diagnosis of gastrointestinal stromal tumours. AB - Gastrointestinal stromal tumours (GISTs), initially presumed to be of "true" smooth muscle origin, encompass a heterogeneous, and as yet incompletely understood, group of mesenchymal tumours with respect to their origin, cellular differentiation, and prognosis. Cellular morphology ranges from predominantly spindle shaped to epithelioid in character, whereas differentiation pathways, as determined primarily by immunohistochemistry and ultrastructure, can vary from indeterminate to myoid and/or neural. Recent work has indicated that the interstitial cells of Cajal, a complex cellular network postulated to act as pacemaker cells of the gastrointestinal tract, which exhibit both myoid and neural features, could be candidates for tumour histogenesis. This would provide a plausible and attractive explanation for the variable differentiation pathways identified in the GIST category to date. Nevertheless, the occasional but undisputed location of GISTs outside the gastrointestinal tract (omentum, peritoneum, and retroperitoneum) might mitigate against such an origin, and their histogenesis remains open to debate. The c-kit proto-oncogene, encoding a growth factor receptor with tyrosine kinase activity, has been postulated to play an important role in tumorigenesis because "gain of function" mutations in this gene, localised to chromosome 4q11-21, are being increasingly identified in hereditary and sporadic cases. Monoclonal and polyclonal antibodies directed at the c-kit gene product expressed on the cell surface (CD117/c-kit) appear to be increasingly helpful in resolving the histopathological differential diagnosis between GISTs and true gastrointestinal smooth muscle neoplasms, schwannomas, and other far less frequently occurring mesenchymal tumours at this site. Although tumours with a clinically benign course appear to be more common than their malignant counterparts, no specific histological criteria have as yet been identified to enable an unambiguous prediction of biological behaviour. Increasing tumour size and mitotic activity favour aggressive tumour behaviour, whereas the prognostic value of germline and somatic mutations within the c-kit proto-oncogene remains to be elucidated further. It is the aim of this synopsis to highlight the relevant fundamental and diagnostic developments with respect to this complex group of neoplasms. PMID- 11215294 TI - A profession? PMID- 11215295 TI - Echo correlation analysis and the acoustic evidence in the Kennedy assassination revisited. AB - A Dallas Police Department recording contemporaneous with the Kennedy assassination contains five impulsive sounds that have the acoustic waveform of Dealey Plaza gunfire. One of the sounds matches the echo pattern of a test shot fired from the Grassy Knoll. The shock wave precedence associated with this pattern is consistent with the muzzle velocity of a .30 calibre rifle. Criticism of the acoustic identifications on statistical grounds is based on erroneous assumptions concerning the assignment of values to the parameters that determine the probability that random noises could resemble gunshot patterns. A conservative estimate of the true value of the probability that the putative Grassy Knoll shot is attributable to random radio noise is no greater than 0.037. Alleged asynchroneity of the sounds with the time of the assassination stemmed from several incorrect assumptions. Whatever their origin, the gunshot-like sounds occur exactly synchronous with the time of the shooting. PMID- 11215296 TI - The New Zealand DNA databank: its development and significance as a crime solving tool. AB - The New Zealand DNA Databank was established following the introduction of legislation in August 1996. Using the Second Generation Multiplex (SGM), DNA profiles from over 13,000 convicted offenders and volunteer donors have been completed to the National DNA Database. Since June 1998, DNA profiles from over 1,400 unsolved crimes have been entered onto the Crime Sample Database. Of all unsolved crimes analysed, 33% are linked to individuals and 21% are linked to other unsolved crimes. Several high profile types of case including homicides, sexual offenses and burglaries are amongst those regularly solved. PMID- 11215297 TI - Glass on clothing and shoes of members of the general population and people suspected of breaking crimes. AB - The outer clothing and footwear of 122 people attending a university gymnasium and a private gymnasium were searched for fragments of glass. Both the surfaces and the pockets of the clothing and the uppers and soles of the footwear were searched. New Zealand forensic glass cases have been reviewed to determine the amount of non-matching glass present on the clothing of people who are suspected of breaking crimes. Data from 114 suspects who had no matching glass on their clothing and shoes were accumulated. Statistical modelling techniques have been applied to the data collected. PMID- 11215298 TI - Level of lung function required to use the Camic Datamaster breath alcohol testing device. AB - In the UK a person who, without reasonable excuse, fails to provide a breath specimen when required to under the 1988 Road Traffic Act, is guilty of an offense. In the past many suspects claim to have experienced difficulty providing breath samples for evidential machines. This paper describes experiments carried out on human subjects, both healthy and suffering a variety of respiratory illness. The experiments were designed to assess the level of respiratory performance required to provide a satisfactory breath sample for the Camic Datamaster. In this study it was found that both actual spirometry values and the percentage of predicted values were both important indicators. PMID- 11215300 TI - California Association of Criminalists. Founders' Lecture. The past, present, and future of criminalistics. PMID- 11215299 TI - Simplified estimation of Widmark "r" values by the method of Forrest. AB - To simplify blood alcohol calculations, tables are presented giving Widmark 'r' values estimated by the method of ARW Forrest (Journal of the Forensic Science Society 1986; 27: 249-252). PMID- 11215301 TI - Death and the maiden. PMID- 11215302 TI - The expert witness. Neither Frye nor Daubert solved the problem: what can be done? AB - Flawed expert scientific testimony has compromised truth finding in American litigation, including in medical malpractice and in product liability cases. The Federal Rules of Evidence and the Supreme Court in Daubert and other cases have established standards for testimony that include reliability and relevance, and established judges as gatekeepers. However, because of lack of understanding of scientific issues, judges have problems with this role, and juries have difficulties with scientific evidence. Professionals and the judiciary have made some advances, but a better system involving the court's use of neutral experts and a mechanism to hold experts accountable for improprieties is needed. PMID- 11215303 TI - Cellular and clinical implications of glutathione. PMID- 11215304 TI - Haem biosynthesis and human porphyria cutanea tarda: effects of alcohol intake. AB - The review describes the structural and biochemical properties of the haem biosynthetic enzyme, uroporphyrinogen decarboxylase (UROD), which sequentially catalyzes the removal of the four carboxyl groups from the acetate side chains of octacarboxylic uroporphyrinogen to form coproporphyrinogen, and the possible biochemical mechanism of the genesis of porphyria cutanea tarda (PCT). The disease is caused when the activity of UROD is significantly reduced. PCT is a multifactorial disease where both inherent and environmental factors such as alcohol, estrogens, halogenated aromatic hydrocarbons and viral infection (mainly hepatitis C) are involved in biochemical and clinical expression. In PCT, hepatic iron plays a key role. Alcohol intake could induce mobilization of iron from protein-bound ferritin. PCT should be managed by avoidance of these toxins and removal of iron by vigorous phlebotomy. Such iron-reduction therapy would provide additional benefit for hepatitis C patients by interferon therapy. PMID- 11215306 TI - Pulmonary histopathology and alteration in cellular pattern of bronchoalveolar lavage fluid in experimental silicosis. AB - Pathogenesis of silicosis is still being evaluated. Cellular and histopathological changes in lung following acute and chronic exposure of quartz in rats have been investigated. Inbred wistar rats were given single intratracheal injection of quartz (10 mg in 0.05 ml saline) in groups of acute model, and inhalation of quartz (40 mg/m3 with air flow 5 l/hr in a simulation chamber, 6 hr/day) in groups of chronic model. The control groups were exposed to vehicles only. Rats were sacrificed on day 3, 5 and 7 of intratracheal injection and after 2, 4 and 8 weeks of inhalation. Total and differential cell counts (TC and DC) were performed in bronchoalveolar lavage fluid (BALF). Histopathology was done in the lungs. There was significant (P < 0.001) increase in TC and significant (P < 0.001) changes in percentage of inflammatory cell counts on DC in the BALF of silicotic rats. Histopathology showed progressive inflammatory and fibrotic response in quartz exposed lungs in both acute and chronic models. The results indicate duration dependent inflammatory changes in lungs of both the models. Changes in cell counts precede the histopathological changes and may serve as early biological marker for detection of silicosis. PMID- 11215305 TI - Cold reactive lymphocytotoxic antibodies in pulmonary tuberculosis: correlation with disease activity and HLA. AB - Cold reactive lymphocytotoxic antibodies (LCA) are more reactive in cold than at 37 degrees C and occur following infection, immunization or vaccination and in various autoimmune diseases. In the present study, LCA activity against T and B lymphocytes has been investigated in patients with pulmonary tuberculosis (PTB), their various clinical sub-groups and consanguineous relatives. Further, the relevance of HLA factors in LCA activity was analyzed. The sera from 144 PTB patients, 52 family contacts and 52 healthy individuals were tested for presence of LCAs by a modified two-stage NIH microlymphocytotoxicity assay. A significant increase in LCA activity against both T (32.6% vs 5.7%, P < 0.0001) and B (59.7% vs 13.4%, P < 0.0000001) cells was observed in PTB patients as compared to healthy controls. There was no correlation between serum LCA activity and sputum acid-fast bacilli status. However, only B cell LCAs revealed significant increase in parallel to disease advancement as assessed by X-ray chest examination. Further, LCA activity was more pronounced in drug responders than drug failure group of patients. No significant difference in the distribution of HLA class I and class II antigens was observed between LCA positive and LCA negative patients. However, panel cells carrying HLA-A1, -A11 and -DR3 were often found reactive in LCA positive patient sera. In household family contacts, LCAs were significantly increased only against B cells as compared to healthy controls (38.4% vs 13.4%, P < 0.01). This study suggests that Mycobacterium tuberculosis infection/exposure could account for the occurrence of LCAs in pulmonary tuberculosis and the strength of these antibodies is related to disease severity and the extent of lung involvement. PMID- 11215307 TI - Polymorphism in heat-shock protein 70-1 (HSP70-1) gene promoter region and susceptibility to tuberculoid leprosy and pulmonary tuberculosis in Asian Indians. AB - Heat shock proteins (HSP) act as immunological target structures either by themselves because of an unusual expression pattern, or they are carrier proteins for immunogenic peptides. A three-allele polymorphism of HSP70-1 promoter region was analysed in random patients with pulmonary tuberculosis (PTB), or with tuberculoid (TT) leprosy and healthy controls from North India. HSP70-1A and HSP70-1C occurred more frequently (> 60%) while HSP70-1B occurred infrequently in this population. Only HSP70-1A allele was significantly increased in TT leprosy as compared to healthy controls (91.8% Vs 71.1%, Pc < 0.03, RR = 4.58). Although a strong association of HLA-DR15 was observed with both of these patient groups in earlier studies, no correlation was found between HSP70-1 promoter alleles with any of the HLA allotypes. Amongst six possible genotype combinations of HSP70-1 promoter allele, only four (A/A, A/B, A/C, C/C) were encountered in Asian Indians. A significant increase of HSP70-1 A/C genotype was observed among DR15 negative PTB patients as compared to DR15 negative controls (87.5% Vs 35.7%, X2 = 8.6, Pc < 0.02) giving highest relative risk of 12.6. These findings suggest that HSP70-1 genes may play a secondary role to HLA-DR in governing susceptibility to mycobacterial infectious diseases. PMID- 11215308 TI - Adrenocorticotropic hormone and growth factor receptors in breast cancer. AB - Tissues from 100 cases of breast cancer were analysed immunohistochemically for the presence of adrenocorticotropic hormone (ACTH) or ACTH-like peptides and expression of c-erbB-2 oncoprotein, epidermal growth factor receptor (EGF-R) as well as oestrogen receptor (ER). Immunopositivity for ACTH was found in 15% cases of infiltrating duct carcinoma of the breast, whereas 38% and 36% breast tumours were positive for c-erbB-2 and EGF-R respectively. While 27% cases were positive for ER. The immunoexpressions of all parameters were higher in breast cancer cases with upper age group (45 years or above) than the patients below 45 years of age. A significant correlation was observed between the tumour grade and the expression of c-erbB-2 oncoprotein. Further, a positive association between the immunoexpression of c-erbB-2 and EGF-R was noticed. Interestingly, a statistically significant relationship was found between the immunopositivity of ACTH and ER. The study reflects a probable association of ACTH or ACTH-like peptides in pathological process of breast cancer. PMID- 11215309 TI - Modification of radiation induced damage in mouse intestine by WR-2721. AB - Intestinal protection in mice against radiation injury by WR-2721 (300 mg/kg body wt, i.p., 30 min before irradiation) was studied after whole body gamma irradiation (0.5, 1.5, 3.0, 4.5, or 6.0 Gy). Crypt survival and induction of apoptosis, and abnormal mitoses in crypt cells in the jejunum were studied on day 1, 3 and 7 after irradiation. Irradiation produced a significant decrease in crypt survival, whereas apoptosis and abnormal mitoses showed a significant increase from sham-treated control animals. Maximum changes in all the parameters were observed on day 1 after irradiation and the effect increased linearly with radiation dose. There was recovery at later intervals, which was inversely related to radiation dose. WR-2721 pre-treatment resulted in a significant increase in the number of surviving crypts, whereas the number of apoptotic cells in the crypts showed a significant decrease from respective irradiated controls on day 1 after exposure. The recovery was also faster in WR-2721 pre- treated animals. It is concluded that WR-2721 protects against gastrointestinal death by reducing radiation induced cell death, thereby maintaining a higher number of stem cells in the proliferating compartment. PMID- 11215310 TI - Anticonvulsant and behavioral actions of triterpene isolated from Rubia cordifolia Linn. AB - Effect of a triterpene isolated from the acetone soluble part of petroleum ether extract of R. cordifolia was studied on convulsions induced by maximum electro shock (MES), electrical kindling and various chemoconvulsants in rats and mice. The effect of triterpene was also investigated on behavior and gamma-aminobutyric acid (GABA) and serotonin (5-HT) content in mouse brain. Triterpene inhibited seizures induced by MES, electrical kindling, pentylenetetrazol (PTZ), and lithium-pilocarpine. However, seizures induced by strychnine were not inhibited. Triterpene reduced locomotion as well as rearing. Pentobarbitone induced sleep was potentiated and amphetamine induced stereotypy was inhibited. The triterpene was found to possess anxiogenic activity. Brain GABA and 5-HT contents were raised by the compound. The study suggests that the triterpene isolated from R. cordifolia bear a potential for further study. PMID- 11215311 TI - Comparative chemotherapeutic efficacy of balhimycin, desgluco-balhimycin against experimental MSSA and MRSA infection in mice. AB - Balhimycin and desglucobalhimycin are glycopeptide antibiotics isolated from an Amycolatopsis spp during the search for novel antibacterials against MRSA from the natural product screening at the Research Centre of formerly Hoechst India Ltd. in Bombay, India. Both compounds show excellent in vitro activity against methicillin sensitive and resistant Staphylococcus aureus (MSSA, MRSA). Both compounds were also found to be active against a number of MRSA strain in the animal studies. The activities were comparable to that of the reference glycopeptides vancomycin and teicoplanin used in these studies. Teicoplanin displayed better in vivo efficacy against S. epidermidis 4929H and Streptococcus pyogenes A77 than either vancomycin or desgluco-balhimycin in the present study. Preliminary studies on pharmacokinetic and acute toxicity were done to get some idea at the early stage of the investigation about the promise of the compounds for development. PMID- 11215312 TI - Effects of a juvenoid, DPE-28, on biology and behaviour of Culex quinquefasciatus, the human filariasis vector. AB - Studies on the effect of a juvenoid, DPE-28 (2,4-dinitrophenyl-2',6'-di tertiarybutyl phenyl ether) on biology and behaviour of Cx. quinquefasciatus showed that the developmental duration, sex ratio, mating success and blood feeding were considerably affected by the exposure of larvae and pupae to the compound. Exposure of fourth instar larvae to 0.007 (EI90) and 0.0019 (EI50) ppm of DPE-28 prolonged the duration of pupation by 58.6 and 52.4 hr and delayed the adult emergence by 35.4 and 17.7 hr in males and 36.8 and 21.1 hr in females respectively. Exposure of freshly ecdysed pupae to 10 and 5 ppm delayed the adult emergence with respect to the control by 54.3 and 32.4 hr in males and 55.2 and 33.2 hr in females respectively. The sex ratio of the adults emerged from treated larvae and pupae was also affected. The female mosquitoes that survived from the exposed fourth instar larvae and pupae exhibited a low blood engorgement ratio. This depression in blood feeding was more pronounced in adults emerged from treated pupae than that of treated fourth instar larvae. A significant proportion of adults emerged from treated larvae and pupae were able to feed only partially. Mating success of the treated populations declined considerably when crosses were made between the males and females emerged from treated fourth instar larvae and pupae. The adults emerged from treated larvae and pupae showed a significant reduction in the oviposition. PMID- 11215313 TI - Teratogenic effects of sinusoidal extremely low frequency electromagnetic fields on morphology of 24 hr chick embryos. AB - To examine the potential teratogenicity of electromagnetic fields (EMF; sinusoidal and rectangular) on development of chick embryos (white leghorn), 221 freshly fertilized chicken eggs (55-65 g) were exposed during first 24 hr of postlaying incubation (38 degrees +/- 0.5 degree C) to 24 different EMFs, with 50Hz repetition rate and 8.007-10.143 mT flux density. Following exposure, the exposed fertilized chicken eggs (n = 8-10) and sham-exposed fertilized chicken eggs (n = 15) were incubated simultaneously for 8 more days and unexposed control fertilized chicken eggs (n = 20) for 9 days in absence of EMFs. The embryos were removed from egg shells and studied blind. All 24 EMF exposed-groups (inside the coil with exposure) showed an increase in the percentage of developmental anomalies compared to sham-exposed (inside the coil with no exposure) and control groups (outside the coil). Further, egg's weight was evaluated on day 9. This variable did not show significant difference between control and exposed-groups. The investigation also covered the measurement of body weight, length of crown to rump, length of tip of the beak to occipital bone, heart and liver weight. Statistical comparison between sham-exposed and control values did not show significant differences, but comparison between 8.007, 8.453 and 8.713 mT exposed groups and control groups showed significant differences; in other exposed groups, the changes were not significant. These results revealed that 50 Hz electromagnetic fields can induce irreversible developmental alterations in 24 hr chick embryos and confirm that its strength could be a determinant factor for the embryonic response to extremely low frequency electromagnetic fields (window effects). PMID- 11215314 TI - Morphogenetic derangements in the reproductive system of Bracon hebetor, a beneficial parasitoid, bred on juvenoid treated host (Corcyra cephalonica) larvae. AB - Effect of juvenoids (hydroprene and methoprene) on the ecto-parasite B. hebetor was investigated by rearing them upon the juvenoid treated ultimate instar host larvae of C. cephalonica. Emerged adultoid wasps of either sexes obtained from treated series showed anatomical deformities in the reproductive systems. Ill developed ovaries with reduced length, terminally free ovarioles and abnormal testicular growth showing non-fusion of lobes were the important abnormal features. Data on measurements of male reproductive system, e.g., width (transverse axis) of testis, length of common vas deferens plus ejaculatory duct and length of accessory gland showed significant difference (P < 0.05) from control. PMID- 11215315 TI - Role of thyroidal and testicular hormones in regulation of tissue respiration in male air-breathing fish, Clarias batrachus (Linn.). AB - In vivo and in vitro effects of thyroidal hormones (MIT, DIT, T3, T4), propyl thiouracil (PTU), testosterone and cyproterone acetate were studied on the rate of tissue (liver, muscle, kidney and brain) respiration of adult male C. batrachus during winter and summer/rainy seasons. Monoiodotyrosine (MIT) and diiodothyrosine (DIT) increased the respiratory rate in a dose-dependent and temperature-independent manner. Triiodothyronine (T3) and thyroxine (T4) stimulated tissue respiration during summer/rainy months but not during winter. PTU decreased tissue respiration during summer/rainy season and also at simulated low temperature. Testosterone invariably stimulated the rate of respiration of the tissues, while in vivo treatment with cyproterone acetate significantly decreased the metabolic rate of all the tissues. The findings suggest that in C. batrachus MIT and DIT may be more important than T3 and T4 at low temperature, endogenous thyroid hormones are involved indirectly in energy metabolism even during winter/at low temperature and testicular hormones are actively involved in the respiration. PMID- 11215317 TI - Epididymal protein secretion and its androgenic control in wall lizards Hemidactylus flaviviridis (Ruppell). AB - The total protein level in different segments of epididymis of normal lizard exhibited noticeable increase from early February to late March of a same reproductive phase. Comparison among the protein level of different epididymal segments showed insignificant variation from anterior to posterior part in early February but in late March, the protein level in posterior segment was appreciably higher than in anterior and middle segments. Further, testosterone induced epididymal protein did not exhibit any significant quantitative variation among different regions. The electrophoretic pattern of luminal fluid from different epididymal regions of normal lizard showed 28 protein bands without any marked regional difference. However, only 16 protein bands could be demonstrated in the epididymal fluid of any region. Unlike molecular size, isoelectric focussing of testosterone induced epididymal proteins revealed that three regions of epididymis differ in their nature of protein. The number of proteins having alkaline pH range in anterior and middle regions were 4 and 3, respectively which increased upto 6 in posterior region. PMID- 11215316 TI - Effects of administration of testosterone on some biochemical correlates in seminal vesicle of Heteropneustes fossilis (Bloch) during preparatory phase: a study correlating changes in plasma testosterone level and testis activity. AB - In the catfish H. fossilis, administration of testosterone (0.25, 0.5, 1 and 2 micrograms/g body weight for 20 days) during mid-preparatory phase (March) increased plasma testosterone, gonadosomatic index, seminal vesicle-somatic index and concentrations of total proteins, fructose and hexosamines in seminal vesicle (SV) and testis in a dose-related manner. In the lowest dosage (0.25 microgram) group, only the hexosamine and SV protein levels were significantly high. Glucose level decreased in a dose-related manner, the decrease being not significant in the 0.25 microgram group. The results indicate that testosterone stimulates SV and testicular secretions of total proteins, hexosamines and fructose in catfish. Decrease in glucose content suggests its conversion into fructose under testosterone stimulation. PMID- 11215318 TI - Hypolipidemic, hypoprostatic and pharmacological activity of oxohexaene polyene antibiotic (HA-1-92). AB - HA-1-92, a new oxohexaene polyene macrolide showed significant hypolipidemic and hypoprostatic activity both in rat and rabbit models. HA-1-92 did not elicit significant effect on blood pressure or respiration in anaesthetized rat or on various isolated tissue preparation studies. PMID- 11215319 TI - In vitro propagation of Acorus calamus Linn.--a medicinal plant. AB - High frequency in vitro propagation protocol was standardized from rhizome explants of A. calamus. Maximum shoot multiplication frequency was obtained on Murashige and Skoog's media supplemented with 4 mg/l 6-benzyl amino purine and 0.5 mg/l indole-3-acetic acid. Regenerated shoots were rooted in vitro or directly transferred to sterile soil and well developed roots were observed within two weeks. The rooted plants were successfully established in the field. PMID- 11215320 TI - Synthesis, free solution capillary electrophoresis separation and toxicity of seven potential impurities of dobutamine. AB - The seven O-methylated analogs of dobutamine [(+/-)-4-[2-[[3-(p-hydroxyphenyl)-1 methylpropyl]amino]ethyl]pyrocatechol, CAS 34368-04-2), a trihydroxy secondary amine, can be considered potential impurities of the latter, the ultimate step of the synthesis of dobutamine being the deprotection of the three phenolic groups. In order to enable the detection and the identification of such a contamination, the di- and the monomethylated derivatives of dobutamine were prepared and their mixture with dobutamine and its trimethoxy precursor completely resolved by Free Solution Capillary Electrophoresis (FSCE). Indeed, the above impurities proved to occur in dobutamine in consequence of improper demethylation conditions and to be significantly more toxic than the latter. PMID- 11215321 TI - Bioavailability and pharmacokinetic profile of dihydroergotoxine from a tablet and from an oral solution formulation. AB - Dihydroergotoxine mesylate (DHETM, CAS 8067-24-1), the combination of the mesylates of four dihydrogenated ergot alkaloid derivatives (dihydroergocornine, dihydroergocristine, alpha-dihydroergocryptine and beta-dihydroergocryptine), is used mainly for age-related cognitive impairment. The bioavailability of DHETM was investigated in a cross-over study on 20 male healthy volunteers to whom two single doses of 9 mg DHETM were administered either in tablets (Orphol spezial) or in oral solution (Orphol forte). DHETM was assayed in serum with a double radioimmunoassay method displaying a satisfactory cross-reactivity with the principal components of DHETM. After administration of tablets the peak of DHETM was (mean +/- SE) 124 +/- 16 pg/ml, the tmax 1.15 +/- 0.21 h, the AUC 790 +/- 93 pg/ml x h and the terminal elimination half-life 7.54 +/- 1.23 h. After oral solution the peak of DHETM was 176 +/- 16 pg/ml, the tmax 0.50 +/- 0.04 h, the AUC 779 +/- 94 pg/ml x h and the terminal elimination half-life 6.13 +/- 0.76 h. The bioavailability of DHETM from tablets vs. that from oral solution differed only by a retard related to the dissolution time of DHETM from the tablets, but not for other pharmacokinetic parameters. The relatively high two single doses of 9 mg DHETM administered to the 20 subjects were well tolerated, causing only known and expected adverse reactions to DHETM (tiredness, headache and vertigo) that did not require discontinuation of the study. PMID- 11215322 TI - Effect of long-term application of Crataegus oxyacantha on ischemia and reperfusion induced arrhythmias in rats. AB - The effect of long-term application of Crataegus oxyacantha on ischemia and reperfusion induced arrhythmias was investigated in Wistar rats on the heart in situ and on Langendorff preparations. Seventeen rats were fed for 8 weeks with 0.5 g/kg b.w. Crataegus extract per day, standardised to 2.2% flavonoids. Twenty age-matched untreated rats served as controls. In the hearts in situ as well as in the Langendorff preparations the left anterior descending coronary artery (LAD) was ligated for 20 min and subsequently reperfused for 30 min. ECG was continuously recorded and the time spent between start of ischemia and onset of arrhythmias was measured. In addition, during ischemia and reperfusion the number of ventricular premature beats and bigemini and the duration of salvos and ventricular flutter and fibrillation were determined. The ischemic area was evaluated in all experiments and coronary flow was measured in Langendorff preparations. In the present experiments, no cardioprotective effects of Crataegus oxyacantha could be detected, neither in the heart in situ nor in the Langendorff preparations. Although the ischemic areas were identical, arrhythmias occurred even earlier in the Crataegus collectives than in the controls. Also the number and duration of ischemia and reperfusion induced arrhythmias tended to occur longer and more frequently in the Crataegus collectives, whilst coronary flow remained unchanged. The phenomenon that Crataegus rather aggravates than prevents arrhythmias may be reduced to a Crataegus induced increase in intracellular Ca(2+)-concentration proven true for the positive inotropic effects of Crataegus. PMID- 11215323 TI - Assessment of skin safety of a new glyceryl trinitrate transdermal patch. Animal and human studies. AB - The experimental models and the studies in man employed to assess the skin and general safety of a newly developed glyceryl trinitrate (GTN, CAS 55-63-0) transdermal patch, hereinafter coded EPI, are described. EPI was found well tolerated by the skin after single or 28-day repeated epicutaneous application on the rabbit, devoid of phototoxicity in the mouse, devoid of skin sensitizing potential in the guinea pig and devoid of photosensitizing effects in the guinea pig. Tested were also, with negative results, the cytotoxic, hemolytic and genotoxic potential, the presence of bacterial endotoxins, the systemic and intracutaneous toxicity, and the possible conjunctival irritant effects. The application of EPI for 14 consecutive days on the thoracic skin of 28 healthy volunteers did not provoke subjective discomfort such as itching, burning or pain, or objective skin lesions. On the application site a light and transient erythema was often found demonstrating the transcutaneous absorption of the vasodilating GTN from the patch. The 14-day application was followed after two weeks by the application of a challenge EPI patch to detect a possible skin sensitization by EPI. No skin reaction was elicited, showing that also in man EPI is devoid of skin sensitizing potential. During the 14-day application of EPI several GTN commonly induced systemic adverse reactions were observed, particularly headache, confirming the systemic bioavailability of GTN from the patch. Headache rapidly disappeared after removal of the patch, in parallel with the decrease of the blood concentrations of GTN and of its active metabolites, consistently with the previous pharmacokinetic findings. This is an advantage of the administration of GTN with the transdermal patch because, in the case of unbearable headache, the patient is relieved by the simple removal of the patch. PMID- 11215324 TI - Hypolipidemic effect of NK-104 and other 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in guinea pigs. AB - Hypolipidemic effects of various HMG-CoA reductase inhibitors (statins) were examined in guinea pigs. After 2-week administration of NK-104 ((+)-monocalcium bis((3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-3, 5-dihydroxy-6 heptenoate), CAS 147526-32-7), simvastatin (SV), pravastatin (PV), fluvastatin (FV), cerivastatin (CV) and atorvastatin (AV) to guinea pigs at various doses, which did not affect body weight, plasma and liver lipids were measured. Liver endoplasmic reticulum (ER) was isolated and measured for lipid content and activity of ER enzymes (NK-104: 3 mg/kg, SV: 30 mg/kg). Each statin except CV dose-dependently lowered total cholesterol (TC), with NK-104 showing the greatest effect. Only NK-104 and AV, long-acting statins, significantly lowered triglycerides (TG). A significant reduction of the liver cholesterol content was observed for NK-104 and AV. The liver TG content increased with dose for SV or PV, but not for NK-104 or AV. The TG content in ER and activity of diacylglycerol acyltransferase of ER, increased with SV and slightly with NK-104. Activity of microsomal triglyceride transfer protein, which is necessary for both apoB particle formation at rough ER and TG droplet production at smooth ER, increased by SV but not by NK-104. It is suggested that statins with prolonged action lower TG by decreasing cholesterol ester supply necessary for very low density lipoprotein formation and by attenuating an increase in TG production at ER after HMG-CoA reductase inhibition. PMID- 11215325 TI - Effects of osutidine (T-593) and its enantiomers on gastric mucosal hemodynamics and mucosal integrity in anesthetized rats. AB - T-593 (osutidine, CAS 140695-21-2) is a new anti-ulcer agent that consists of two enantiomers, (+)-(R)-T-593 and (-)-(S)-T-593. The present study was designed to investigate the effects of T-593, (+)-(R)-T-593 and (-)-(S)-T-593 on ethanol induced gastric damage in rats. Rats were given intraperitoneal administration of vehicle, racemic T-593, (+)-(R)-T-593 or (-)-(S)-T-593. 30 min later, the rats intragastrically received a 1-ml solution of 40% ethanol, and 30 min thereafter, they were sacrificed for assessment of gastric damage. Gastric hemodynamics were assessed by reflectance spectrophotometry and laser Doppler flowmetry during the experiment. Gastric damage was significantly suppressed by racemic T-593 in a dose-dependent manner. While 60 mg/kg of (+)-(R)-T-593 and (-)-(S)-T-593 also suppressed ethanol-induced gastric injury, the same dose of racemic T-593 exerted the most potent anti-ulcerative activity. Both (+)-(R)-T-593 and racemic T-593 increased gastric mucosal blood flow and abolished gastric mucosal blood flow stasis induced by 40% ethanol. Although (-)-(S)-T-593, which antagonizes histamine H2-receptors, exerts an antiulcerative effect, (+)-(R)-T-593 also protects the gastric mucosa from ethanol-induced injury, possibly by influencing gastric mucosal hemodynamics. Thus racemic T-593 may protect the gastric mucosa by antagonizing H2-receptors and by enhancing gastric circulation in rats. PMID- 11215326 TI - General pharmacology of IY-81149, a new proton pump inhibitor. AB - IY-81149 (2-[(4-methoxy-3-methyl)-2-pyridinyl]methylsulfinyl -5-(1H-pyrrol-1-yl) 1H-benzimidazole, CAS 172152-36-2) is a new proton pump inhibitor and expected to be an antiulcer drug. Its general pharmacological effects were studied in this paper. The doses given were vehicle control, 0.3, 1, 3, 100, 300 and 1000 mg/kg and were administered orally. The animals used in this study were mouse, rat, guinea pig and beagle dog. IY-81149 decreased spontaneous locomotor activity at 1000 mg/kg and showed a weak effect in motor performance at 300 and 1000 mg/kg. IY-81149 prolonged the hexobarbital-induced sleeping time dose dependently at 100, 300 and 1000 mg/kg. Oral administration of IY-81149 caused a dose-dependent hypothermic effect up to 300 mg/kg and showed analgesic effect at 1000 mg/kg. IY 81149 produced an antisecretory effect in pylorus ligated rats. The total gastric volume and acidity were significantly decreased at doses ranging from 1 to 3 mg/kg. However, IY-81149 had no effects on general behavior, did not show anticonvulsant activity, and did not affect blood pressure and heart rate, LVP (left ventricular peak systolic pressure), LVEDP (left ventricular end diastolic pressure), LVDP (left ventricular developing pressure), DP (double product), HR (heart rate), CFR (coronary flow rate), smooth muscle contraction, respiration, intestinal transport and renal function. These findings demonstrate that IY-81149 possesses weak central nervous system action and inhibitory effects on microsomal enzymes and gastric secretion after single administration. The results suggest that IY-81149 does not exert any notable pharmacological effects on the cardiovascular system, autonomic nerve system or smooth muscle function at all doses tested. PMID- 11215327 TI - Dose-related effects of controlled release dihydrocodeine on oro-cecal transit and pupillary light reflex. A study in human volunteers. AB - It is well accepted that long-term administration of opioids results in a dose related constipation. No data so far have demonstrated conclusively whether such constipation is also seen after intake of a controlled release formulation. It was therefore of interest to evaluate whether increasing doses of a controlled release formulation of dihydrocodeine (DHC, CAS 125-28-0) after oral administration also induces a dose-related increase in constipation. Additionally, it was of interest to study whether such a peripheral opioid related side effect is also seen in another, central receptor-mediated effect, the constriction of the pupil, at clinically relevant doses. Twelve volunteers were given controlled release DHC (60 and 120 mg, respectively) or placebo orally within a randomized, double-blind cross-over study. In order to determine the degree of constipation, oro-cecal transit time was measured using the H2 exhalation test. Additionally, in order to evaluate a centrally mediated effect, the response of the pupil to light was quantified using the pupillary light reflex technique. Both, peripherally and centrally mediated effects were compared to placebo. DHC at both dosages induced a significant (p < 0.01) prolongation of oro-cecal transit time when compared to placebo. However, prolongation of oro cecal transit was not significantly longer when comparing the lower (60 mg) with the higher dose (120 mg). DHC also induced a significant (p < 0.005) depression of the pupillary light reflex from 53.9 mm (control) to 8.3 and 7.4 mm, respectively. Similar to intestinal transit, the pupillary light reflex was not significantly different among the two doses of DHC. Also, both dosages induced a similar amount of side effects. Tiredness and dry mouth were reported in 80% after both doses while vertigo was reported in 5% and 1% complained of headache. None of the volunteers reported nausea or emesis. It is concluded that opioid receptor sites, which are located in the plexus myentericus of the intestinal wall, are responsible for the delay in propulsion. Because of the controlled release of a fixed amount of DHC over time there is constant binding of the ligand followed by a constant conformational change of peripheral and central receptor sites. Thus constant release induces no dose-related increase in oro cecal transit and inhibition of the pupillary light reflex. PMID- 11215328 TI - Antimicrobial activity of new coumarin derivatives. AB - A preliminary exploration of coumarin analogs as novel antimicrobial agents was carried out to determine the basic features of the structure responsible for the observed biological activity. The substituents ester or carboxylic acid on the coumarin ring were needed to have potent inhibitory activity against both Gram positive and Gram-negative bacteria. The presence of phenolic hydroxyl group and/or carboxylic acid was necessary to possess higher activity against Helicobacter pylori. PMID- 11215329 TI - [Physical chemical, pharmacological and toxicologic properties of fomocaine metabolites] . AB - Fomocaine (4-[3-(4-phenoxymethylphenyl)-propyl]-morpholine, CAS 17692-39-6) is a highly effective local anaesthetic of low toxicity. The drug, which causes no allergic response, was introduced in the German Extrapharmacopoeia (DAC). Fourteen metabolites are formed after oral administration to rat and beagle dog. Less than 5% fomocaine are excreted unchanged. The metabolites were synthesized and their physico-chemical properties were investigated. No metabolite caused a surface or conduction anaesthesia with the exception of 2-hydroxyfomocaine (O/Se 4). After topical and parenteral administration irritation could not be observed. All metabolites except O/Se 10 and O/Se 11 showed a lower toxicity than fomocaine. In both species O/Se 10 and O/Se 11 are formed only in a small amount and are detoxified by conjugation. PMID- 11215330 TI - Antifungal activity of some mono, bis and quaternary Mannich bases derived from acetophenone. AB - The development of resistance to current antifungal therapeutics drives search for new effective agents. Some Mannich bases have antifungal activity, but no information is available regarding the antifungal activity of acetophenone derived Mannich bases. Mono Mannich bases of acetophenone 1-3 were synthesized and converted into their corresponding bis derivatives, 5-7. Representative quaternary derivatives 4 and 8 were also synthesized. Antifungal activities of the compounds were evaluated using some yeasts and dermatophytes in vitro. Mono Mannich base 3 and quaternary compounds 4 and 8 were found to be 2-16 times more potent than the reference compound amphotericin B against dermatophytes: Trichophyton rubrum, Trichophyton mentagrophytes, and Microsporum canis. Compounds 4 and 8 were also found to be 2 times more effective compared with amphotericin B against the yeast Saccharomyces cerevisiae. Quaternization procedure improved the biological activity dramatically, whereas conversion of mono Mannich bases to corresponding bis derivatives generally did not affect antifungal activity. Our results suggest that acetophenone derived mono Mannich base 3 and quaternary derivatives 4 and 8 may serve as leading compounds for further studies to develop new antifungal agents with their highly potent antifungal activity. PMID- 11215331 TI - Immunopharmacological in vitro effects of Eleutherococcus senticosus extracts. AB - The objective of these investigations was to further elucidate the immunopharmacological profile of fluid extracts of Eleutherococcus senticosus and to identify the specific role of its characteristic eleutherosides B and E. An ethanolic dry extract of Eleutherococcus senticosus was used as starting material for the isolation of the eleutherosides B and E. Immunopharmacological studies included expression of major histocompatibility complex class I and II molecules by rat bone marrow-derived mononuclear phagocytes, human lymphocyte marker flow cytometry, and in vitro testing of human lymphocyte functions. In contrast to the isolated eleutherosides B and eleutherosides E and the re-mixed eleutherosides B and E, the whole ethanolic fluid extract of Eleutherococcus senticosus was able to induce and enhance interleukin-1 and interleukin-6 but not interleukin-2 production in vitro. The effective concentration of the whole ethanolic extract ranged from 1.0-0.1 mg/ml for the enhancement of interleuking-1 alpha production and 1.0-0.03 mg/ml for the enhancement of interleukin-6 production. It is concluded that the observed enhancing immunopharmacological activities on acute phase response mediators are best exhibited by the induction with whole ethanolic extracts whereas the species-specific and characteristic eleutherosides B and E are not associated with these activities. PMID- 11215332 TI - Pharmacokinetics and pharmacodynamics of recombinant human erythropoietin in rats. AB - The pharmacokinetics and pharmacodynamics of recombinant human erythropoietin (rh EPO; CAS for EPO: 11096-26-7) after repeated intravenous and subcutaneous administrations in rats were studied. Administration of rh-EPO by both routes caused significant increases in hematocrit. The pharmacokinetics of rh-EPO after intravenous and subcutaneous administration exhibited nonlinearity. The pharmacodynamics of rh-EPO was analyzed using the maximum effect (Emax) and sigmoid maximum effect (sigmoid Emax) models. Both models involved the assumption that rh-EPO in plasma would stimulate the proliferation of erythroid progenitor cells. Akaike's information criterion for the Emax model was lower than that for the sigmoid Emax model, suggesting that the Emax model might be an optimal model. The rh-EPO concentration at which the effect is half of the maximum was 0.383 ng/ml. This pharmacodynamic analysis suggests that the maintenance of effective plasma concentration might be important for the efficacy of rh-EPO. PMID- 11215333 TI - [Are uranium weapons to blame for leukemia cases? A little bit of atomic warfare in the Balkans? (interview by Dr. Beate Schumacher)]. PMID- 11215334 TI - [Child abuse by the parents? Proper response]. PMID- 11215335 TI - [Gastrointestinal reflux. When sour is not happy]. PMID- 11215336 TI - [Sclerosing, coagulating, ligating... Managing hemorrhoids!]. AB - Hemorrhoids are a pathophysiological consequence of hyperplasia of the corpus cavernosum recti, and can be classified into three grades of severity. Clinically, they usually manifest in the form of peri-anal bleeding, a diffuse sensation of discomfort, itching and secretion of mucus. The diagnosis is established on the basis of the dinical presentation. Treatment is mainly conservative, but is likely to be successful only in the early stages. Already second degree symptomatic hemorrhoids require definitive treatment. Although peri anal thrombosis is sometimes a very painful condition, it is usually harmless. If pain is severe, surgical incision is indicated. PMID- 11215337 TI - [Lesions around the rectum. Diagnosing and treatment abscesses and fistulas]. AB - Anorectal abscesses and fistulas are among the most common anorectal lesions. They represent different phases of one and the same condition, the abscess being the acute manifestation, the fistula the chronic form. In the event of a strong suspicion, rapid referral to hospital, preferably one specializing in proctology, is indicated. The treatment of choice of both abscesses and fistulas is surgery. Abscesses are widely incised and decompressed. Fistulas showing signs of fresh secretion may be treated initially by the insertion of a thread, and subsequently undergo definitive surgical treatment. The surgical procedure is determined by the site of the fistula. Attendant risks include recurrence and incontinence. When fistulas occur in Crohn's disease, the indication for surgical treatment must be stringently applied. In the absence of complications, postoperative healing of the wound should be checked regularly. PMID- 11215338 TI - [An end to smearing! Detecting and treating rectal rectal and anal prolapse]. AB - Rectal prolapse is defined as the invagination of the entire wall of the rectum into or through the lumen of the anal canal. In the main it is a disorder of elderly women. The leading symptom is a sensation of incomplete defecation. Patients commonly complain of incontinence of varying severity, tenesmus, unsuccessful straining, and the passage of blood and mucus in the stools. The diagnosis is based on the history and physical examination. Equipment-based diagnostic procedures serve treatment planning. For therapy, a range of possibilities are available. Anal prolapse is categorized as third-degree hemorrhoidal disease, and the diagnosis can be made by simple inspection. Reduction may be attempted during digital examination of the rectum. Treatment is determined by the clinical presentation. PMID- 11215339 TI - [Paths to sexual satisfaction. What will stimulate the tired man?]. PMID- 11215340 TI - [Science or quackery? Complimentary medicine: mental healing]. PMID- 11215341 TI - [Identification record for defibrillator patients. Basic documentation for ICD]. PMID- 11215342 TI - [Disorders of thyroid function. Efficient diagnosis in general practice]. PMID- 11215343 TI - [CD-ROM for malingerers. Deceiving the physician by simulation]. PMID- 11215344 TI - [Instead of benzodiazepines. An antidepressant as sleep aid]. PMID- 11215345 TI - [Diabetes and the heart. Sweet hearts beat for a shorter time]. PMID- 11215346 TI - [Insulin analogs. More precise control for diabetic patients is possible]. PMID- 11215347 TI - [When standard therapy fails. New therapy options in chronic hepatitis C]. PMID- 11215348 TI - [Erectile dysfunction in coronary heart disease. No fear about the blue pill]. PMID- 11215349 TI - [Stomach-saving "Coxibs". No reason for therapeutic risks]. PMID- 11215350 TI - [The aging woman, an asexual being? Erotically more active than previously assumed]. PMID- 11215351 TI - [Pain therapy. Which analgesics for elderly patients?]. PMID- 11215352 TI - Bold approach curtails bronchitis antibiotic use. PMID- 11215353 TI - New outpatient procedures for GERD present alternatives. AB - Heartburn getting serious clinical attention. Gastroesophageal reflux disease, or GERD, can cause inflammation of the vocal cords or even cancer of the esophagus. But even the more prosaic symptoms should be enough to get clinicians to investigate these two new surgical interventions for heartburn. PMID- 11215354 TI - Heart failure intervention cuts return trips to hospital. AB - Hospitals collaborate to cut heart failure readmissions. A consortium of hospitals in New York state collaborate to reduce readmissions among their heart failure patients without compromising quality. The eye-opening part was discovering the cause of readmissions. PMID- 11215355 TI - Sickle cell center provides model for management of chronic disease. AB - Coordination, round-the-clock care reshapes sickle cell care. Sickle cell patients at Grady Health System in Atlanta know what it's like to be kept waiting interminably in the emergency department, sick and in pain. They even know how it feels to be mislabeled as drug addicts. No more. The Sickle Cell Center at Grady brings high quality care to such patients, improving outcomes, lowering costs, and increasing the satisfaction of those who use it. PMID- 11215356 TI - Boost outcomes--add a clinical pharmacist to the team. AB - Add a clinical pharmacist to the heart care team. Duke clinicians did, and found they could lower heart-failure related events as well as lower overall costs. The landmine is reorganizing the referral and care patterns in the hospital. PMID- 11215357 TI - [Therapy of active Crohn disease with Boswellia serrata extract H 15]. AB - BACKGROUND: The purpose of this clinical trial was to compare efficacy and safety of the Boswellia serrata extract H15 with mesalazine for the treatment of active Crohn's disease. PATIENTS AND METHODS: Randomised, double-blind, verum controlled, parallel group comparison for which 102 Patients were randomised. The per protocol population included 44 patients treated with H15 and 39 patients treated with mesalazine. As primary outcome measure the change of the Crohn Disease Activity Index (CDAI) between the status of enrolment and end of therapy was chosen. H 15 was tested on non-inferiority compared to standard treatment with mesalazine. RESULTS: The CDAI between the status of enrolment and end of therapy after treatment with H15 was reduced by 90 and after therapy with mesalazine by 53 scores in the mean. In this non-inferiority-trial the test hypothesis was confirmed by the statistical analysis. The difference between both treatments could not be proven to be statistically significant in favor to H15 for the primary outcome measure. The secondary efficacy endpoints confirm the assessment of the comparison of H15 and mesalazine. The proven tolerability of H15 completes the results of the shown clinical efficacy. CONCLUSIONS: The study confirms that therapy with H15 is not inferior to mesalazine. This can be interpreted as evidence for the efficacy of H15 according to the state of art in the treatment of active Crohn's disease with Boswellia serrata extract, since the efficacy of mesalazine for this indication has been approved by the health authorities. Considering both safety and efficacy of Boswellia serrata extract H15 it appears to be superior over mesalazine in terms of a benefit-risk evaluation. PMID- 11215358 TI - [Diagnosis and therapy of ulcerative colitis--results of an evidence-based consensus conference of the German Society of Digestive and Metabolic Diseases]. PMID- 11215359 TI - [Guidelines of the DGVS. Clinical diagnosis. German Society of Digestive and Metabolic Diseases]. PMID- 11215360 TI - [Guidelines of the DGVS. Histopathological diagnosis. German Society of Digestive and Metabolic Diseases]. PMID- 11215361 TI - [Guidelines of the DGVS. Nutrition. German Society of Digestive and Metabolic Diseases]. PMID- 11215363 TI - [Guidelines of the DGVS. Fulminant process. German Society of Digestive and Metabolic Diseases]. PMID- 11215362 TI - [Guidelines of the DGVS. Acute process. German Society of Digestive and Metabolic Diseases]. PMID- 11215364 TI - [Guidelines of the DGVS. Chronic active course. German Society of Digestive and Metabolic Diseases]. PMID- 11215365 TI - [Guidelines of DGVS. Remission. German Society of Digestive and Metabolic Diseases]. PMID- 11215366 TI - Prospective study comparing human albumin vs. reinfusion of ultrafiltrate-ascitic fluid after total paracentesis in cirrhotic patients with tense ascites. AB - Although, total paracentesis associated with human albumin substitution has shown to be a rapid, effective and safe treatment of diuretic refractory ascites in advanced liver cirrhosis, it implies high costs and has a limited availability. Therefore an alternative procedure the reinfusion of concentrated ascites has gained popularity in recent years (Smart et al. 1990; Grazioto et al. 1997). It was the aim of the study to compare human albumin substitution vs. reinfusion of ascitic-ultrafiltrate after total paracentesis. 35 patients with cirrhosis and tense ascites received total paracentesis associated with either human albumin (5 8 g/l ascites) (= group A) or reinfusion of an ascitic-ultrafiltrate fluid by means of hemofiltration technique (= group B). The mean volume of ascites removed was 9.41 (2.1-20.0) in group A and 11.41 (6.5-21.0) in group B. No significant differences in serum electrolytes, liver and renal function, coagulation profiles and hormones of the renin-angiotensin-aldosterone system were observed during hospitalization. In both groups sodium excretion increased significantly. 43% of the patients in group B developed pyrexia and chill after reinfusion of the ascitic-ultrafiltrate fluid. In one patient an anaphylactic bronchospasm occurred requiring IUC-treatment. The treatment cost in case of human albumin were 326.-DM vs. 290.-DM for each patient treated with ascitic-ultrafiltrate fluid reinfusion. The probabilities of hospital readmission and survival were similar in both groups during follow-up. The results indicate that i.v. infusion of ascitic ultrafiltrate fluid is as effective as total paracentesis and albumin infusion in case of diuretic refractory ascites. However, according to the costs of instruments and staff and due to the significant allergic reactions caused by ascitic fluid it cannot be considered as a real alternative to albumin substitution. PMID- 11215367 TI - [Guidelines of the DGVS. Prevention of carcinoma. German Society of Digestive and Metabolic Diseases]. PMID- 11215368 TI - [Guidelines of the DGVS. Surgical therapy. German Society of Digestive and Metabolic Diseases]. PMID- 11215369 TI - [Guidelines of the DGVS. Pouchitis. German Society of Digestive and Metabolic Diseases]. PMID- 11215371 TI - [Guidelines of the DGVS. Psychosomatic aspects. German Society of Digestive and Metabolic Diseases]. PMID- 11215370 TI - [Guidelines of the DGVS. Extraintestinal manifestations. German Society of Digestive and Metabolic Diseases]. PMID- 11215372 TI - [Ultrasound diagnosis of Meckel diverticulitis in adults]. AB - Meckel's diverticulitis is a rare disease. In addition to physical examination, abdominal ultrasound can help to pinpoint the diagnosis. By presenting a case report we would like to demonstrate the typical ultrasonographic findings in acute Meckel's diverticulitis and differentiate it from acute appendicitis. A 60 year-old patient was admitted to our hospital with the diagnosis of acute appendicitis. Abdominal ultrasound was performed and a blind ending, liquid filled segment of small bowel in the right lower quadrant of the abdomen found. This segment was not compressible, no peristalsis was evident, nor was there any anatomical association with the cecum. Locally we found free fluid and hints of inflamed mesenteric fatty tissue. A perforated Meckel's diverticulum was diagnosed and confirmed intraoperatively. The major ultrasonographic difference between an inflamed Meckel's diverticulum and acute appendicitis is its anatomical location. In contrast to the appendix there is no association with the cecum. A diameter of up to 40 mm and a well-defined wall of small bowel with 3 definite layers visible by ultrasound may help to distinguish between a Meckel's diverticulum and the appendix. PMID- 11215373 TI - [Secondary high-grade MALT lymphoma of the stomach in a 69-year-old patient with gastrocolic fistula]. AB - A 69-year-old man was referred to our department with an exorbitant foetor ex ore, dysphagia and dyspepsia. Upper endoscopy had been performed prior by an outpatient gastroenterologist and the patient had received an eradication therapy for a Helicobacter pylori-induced gastritis. At admission upper endoscopy showed a gastric ulcer which drained a stinking fluid. Endosonography, computed tomography and an upper gastrointestinal series with water soluble media revealed a gastrocolic fistula. Multiple biopsies showed a low-grade gastric MALT lymphoma. Therefore, a surgical reconstruction with Roux-en-Y esophagojejunostomy and transverso-descendostomy was performed. The histology of the completely removed stomach revealed a high-grade Non Hodgkin Lymphoma (NHL) with parts of a low-grade NHL. 3 weeks after surgery chemotherapy was started with the CHOP regime which was well-tolerated by the patient. PMID- 11215374 TI - Oral zinc therapy in patients with supposed mild zinc deficiency--a critical review. AB - The importance of zinc in many processes of diseases remains unclear up today. Nevertheless many biochemical or clinical studies let support a high clinical relevance of trace elements especially zinc in the therapeutic concepts of diseases. Unfortunately the border between severe (or real) and mild (or subclinical) zinc deficiency is not clear defined. In addition methodical problems in determination of trace elements and misinterpretations of study results lead to unjustified assignment from several diseases in the group of zinc deficiency disorders. Another current problem is the consideration of bioavailability of oral commercial trace element products. Especially the regulation of zinc uptake in human under normal conditions and in case of zinc deficiency is not clear at this time. These problems let become tangled the actual literature for the clinical active physician at the field of zinc. In this mini review there is given an overview about published clinical studies with oral zinc supplementation in the past years. PMID- 11215375 TI - [Investigational new drugs among glycoprotein IIb/IIIa-receptor antagonists]. AB - Glycoprotein IIb/IIIa receptors play an important role in platelet aggregation by binding fibrinogen. Drugs that antagonize this binding have been developed for the treatment of thrombotic diseases including acute coronary syndrome. These drugs are of four main types: [1] monoclonal antibody, [2] synthetized peptide, [3] non-peptide, and [4] oral antagonist. Since these drugs inhibit the final step in platelet aggregation, i.e., binding of fibrinogen to the platelet membrane, they were expected to 1) have high specificity for inhibiting platelet aggregation, 2) inhibit any kind of aggregation regardless of stimulation, 3) have high potency in aggregation suppression. As a result of large clinical trials, however, monoclonal antibody alone was revealed to be effective, but non peptide and oral antagonists were ineffective. The possible mechanisms that lead to such inefficiency are: 1) difference in binding duration to platelets, 2) concomitant suppression of other adhesion molecules beside IIb/IIIa, 3) difference in binding site in the receptor and presence of a partial agonist effect, 4) aggregation promotion or induction of apoptosis via caspase-3 activation, 5) modified aggregation by gene polymorphism. New findings on platelet physiology through studying ways to overcome the above problems will lead to the development of new drugs and treatment. PMID- 11215376 TI - [Aggregation of human blood platelets by remnant-like lipoprotein particles]. AB - The action of lipoprotein lipase on chylomicrons (CM) and very low density lipoproteins (VLDL) produces remnant lipoproteins (RLP) that are rich in triglycerides, cholesterol and apolipoprotein E (apo E). Apo E serves as a ligand for the LDL receptor and mediates uptake of RLP by macrophages, vascular wall and other cells that express the LDL receptor. Uptake of RLP can profoundly alter the physiology of cells and promote atherosclerosis and thrombosis. Like RLP, blood platelets also have roles in atherosclerosis and thrombosis; hence it is likely that RLP can influence platelet activity as well. Platelet aggregation was assessed by measuring the loss of single platelets. Apo E3/3-rich RLP derived from normal human plasma VLDL and CM were prepared by an immunoseparation method. At 2.5 to 10 microliters, RLP induced platelet aggregation that increased with the dose of RLP, but decreased it at 25 to 200 microliters. Unlike apo E3/3-rich RLP, apo E4/3 (heterozygous phenotype) rich RLP caused platelet aggregation in a dose-dependent manner, without producing a bell-shape dose-response relationship. Scanning electron microscopy revealed that activated platelets had adhered to and formed aggregates on the red cell membrane. The platelet response was unaffected by aspirin, but was inhibited by apyrase (an ADP scavenger), 2-chloroadenosine (a platelet ADP-receptor antagonist) and cilostazol, a phosphodiesterase type III inhibitor. It is thought that RLP cause leakage of ADP from red cells, which then mediates platelet aggregation. PMID- 11215377 TI - [New anticoagulants]. AB - The quest to develop new antithrombotic agents has been stimulated by clinical needs and by advances in biotechnology that have made it possible to produce drugs that target specific steps in thrombogenesis. Established anticoagulants such as unfractionated heparin and the coumarins are effective, but have two major limitations: narrow therapeutic windows and highly unpredictable dose response relationships. Consequently, these drugs often cause complications such as serious bleeding that require close monitoring of their use by laboratory tests to balance safety and effect. These limitations provided the impetus for the development of new anticoagulants that inactivate thrombin, factor Xa, factor IXa or the factor VIIa/tissue factor complex. Similarly, agents that enhance the protein C anticoagulant pathway have also been developed. Of these, direct thrombin inhibitors, soluble thrombomodulin, protein C, and activated protein C have been evaluated clinically for parenteral administration. However, there is enormous interest in the development of safer and more effective oral anticoagulants. In the future, such orally active direct inhibitors of thrombin and factor Xa, if they can be given safely without the need for laboratory monitoring, may replace the coumarins for the long-term treatment of thromboembolic disorders. To achieve these goals, these compounds need high, consistent oral bioavailability. PMID- 11215379 TI - [Anti-thrombotic effect of activated protein C]. AB - Protein C (PC) is an important anticoagulant protein in blood and converted to its active form, activated protein C (APC), by thrombin bound with thrombomodulin. APC exhibits an anticoagulant effect by the inactivation of FV a and FVIII a. In addition, APC exerts a profibrinolytic effect by inactivation of PAI-1 and inhibition of TAFI activation. APC is strongly anti-thrombotic because of its anticoagulant and profibrinolytic effect. APC has gamma-carboxyglutamic acid residues that bind to acidic phospholipids expressed on activated platelet or injured endothelial cells. Thus APC works only at the site where clots are formed and has a weak effect in primary hemostasis; this means that the use of APC is expected not to have any hemorrhagic risk. In both DIC animal models and clinical studies, we confirmed safer amelioration by APC than heparin. Recently, a specific receptor for PC/APC was found on endothelial cell membrane and anti inflammatory effects of APC were also reported. Thus APC is thought to play an important regulatory role in blood coagulation, fibrinolysis and inflammation, especially in thrombotic diseases. PMID- 11215378 TI - [Thrombomodulin]. AB - Thrombomodulin (TM), a membrane-bound receptor for thrombin on the endothelial cell surface, contributes to the regulation of the coagulation system. TM is known to exist in human plasma and urine as soluble forms. We purified soluble TM from human urine (MR-33) and investigated the anticoagulant effects of MR-33 in vitro and in vivo. In human plasma, MR-33 inhibited not only the procoagulant activity of thrombin, but also the thrombin generation via accelerating the thrombin-catalyzed protein C activation. In rat disseminated intravascular coagulation (DIC) models, intravenous infusion of MR-33 improved the hematological abnormalities without excessive prolongation of APTT and bleeding time. Benefit (dose required for 50% inhibition of fibrinogen decrease: ED50) to risk (minimum dose required for significant prolongation of bleeding time) ratio was 1:27 for MR-33. Furthermore, the anticoagulant activities of MR-33 was independent of AT III activity, and MR-33 was effective on heparin-resistant DIC models with low AT III level in rats. Intravenous injection of MR-33 prevented the endotoxin-induced increases in TAT, TNF-alpha and IL-6 level and pulmonary vascular permeability in mice. These results indicate that MR-33 may be a clinically useful antithrombotic agent with reduced risk for hemorrhage, and this drug also has anti-inflammatory effects. Clinical trials of MR-33 for the treatment of DIC are now in progress in Japan. PMID- 11215380 TI - [Regulatory mechanism of fibrinolysis system by thrombin activatable fibrinolysis inhibitor (TAFI)]. AB - Thrombin-activatable fibrinolysis inhibitor (TAFI) is a 60-kDa plasma protein that has been shown to be identical to plasma carboxypeptidase B (CPB) and carboxypeptidase U (CPU). TAFI is activated by thrombomodulin (TM)-bound thrombin and specifically removes the C-terminal Lys and Arg by its CPB activity. One of its target substrates is the C-terminal Lys residue in the alpha-chain of plasmin digested fibrin, which is critical for plasminogen binding to fibrin. Thus, its removal seems to be the main mechanism through which TAFI inhibits fibrinolysis. In this article, relevance of C-terminal Lys of plasmin-digested fibrin in fibrinolysis is described, and then possible roles of TAFI and TM-bound thrombin in a cross-talk between coagulation and fibrinolysis are discussed. PMID- 11215381 TI - [Pharmacological aspects of mammalian hibernation: central thermoregulation factors in hibernation cycle]. AB - Hibernation in mammalians such as hamsters is a physiological state characterized by an extreme reduction of various functions such as body temperature and metabolism. Under such severe conditions, the central nervous system (CNS) activity is maintained at a functionally responsive level. Although hibernation is an interesting behavioral state, the physiological mechanisms of the introduction to and/or the arousal from hibernation have not been clearly defined. Intracerebroventricularly (i.c.v.) injected adenosine produces hypothermia in various animals. The effect of adenosine is generated by A1 receptors and is caused by the suppression of the thermogenesis center of the posterior hypothalamus. At on ambient temperature of 5, i.c.v. injected N6 cyclohexyladenosine (CHA) adenosine A1-receptor agonist induces profound hypothermia in hamsters. Although the time course of the descent of body temperature coincided with that of entry into natural hibernation, the effect was not antagonized by 8-cyclopentyltheophyllin (CPT), an adenosine A1-receptor antagonist. However, i.c.v. injection of CPT elevated the body temperature and interrupted hibernation, albeit the deep-phase (post-entry 30 h) was unaffected. This result suggests that a different system may suppress the thermogenesis center in the deep hibernation phase. Interestingly, i.c.v. injected thyrotropin releasing hormone (TRH) elevated the body temperature in both hibernation phases in hamsters. These findings suggest that the central adenosine and TRH play important roles in thermoregulation and that the new thermogenesis system, activating in low-body temperature, is induced in naturally hibernating animals. PMID- 11215382 TI - [Delayed emesis induced by the chemotherapeutic agent doxorubicin hydrochloride in dogs]. AB - The occurrence of delayed emesis induced 24 h after the administration of a non platina chemotherapeutic agent, doxorubicin hydrochloride (doxorubicin), as well as behaviors such as feeding, drinking and defecation were examined in dogs. A single intravenous administration of 2 mg/kg doxorubicin induced emesis within 24 h of administration in some dogs, while delayed emesis was observed 24 h after administration in all dogs. This delayed emesis emerged strongly at day 3 or 4 and decreased at day 5. Hypophagia, the decreased frequency of drinking and the increased frequency of defecation were induced shortly after delayed emesis. Twenty-four hours after the administration of doxorubicin, a daily dose of 0.3 and 1 mg/kg/day, p.o. azasetron, a 5-HT3 antagonist, was administered for 4 days. Doxorubicin-induced delayed emesis was observed to decrease by about 30 and 50%, respectively. This result suggests that 5-HT3 receptors play a role in the mechanism of delayed emesis. Azasetron was found to improve the increased frequency of defecation, but exerted no obvious effect on hypophagia or on the decreased frequency of drinking. Taken together, we suggest that doxorubicin induced emesis in dogs is a useful method to study further the mechanisms of delayed emesis and to investigate novel therapeutic agents against delayed emesis. PMID- 11215383 TI - [Legal matters in guardianship of adult patients with mental disorder]. PMID- 11215384 TI - [Future task of the Japanese Society of Juvenile Psychiatry]. PMID- 11215385 TI - [On the importance of the "decision-making model" view of diagnosis as a clinical framework in psychiatry]. AB - After the advent of DSM-III, operational diagnostic criteria, along with the classification of disorders using such criteria, received considerable attention, and many studies on the reliability and validity of psychiatric diagnosis were conducted worldwide. Operational methodology was applied to diagnosis and classification, especially, in the area of research, and has contributed greatly to advances in reliable and refined clinical research. Such methodology, however, has not necessarily been accepted as a guiding principle in the area of clinical practice by all psychiatrists. Rather, some psychiatrists, especially more experienced psychiatrists, took a somewhat negative attitude toward the use of operational methodology. The author contends that one of the causes for the relatively poor acceptance of operational methodology in the area of clinical practice lies in the "classification model" view of diagnosis that forms the implicit background for the methodology. From a clinical perspective, it is not from the "classification model" basis but rather, from the "decision-making model" basis that the actual process of clinical diagnosis in psychiatry is explained properly. This is a very important point, because the latter model is potentially more useful both to psychiatric patients and to researchers in psychiatry than the former model. There have been however, few reports in psychiatry that highlight the importance of this model as the clinical framework. The author analyzes the limitations of the "classification model" view, and then, based on this analysis, lists prerequisites that a model for the framework of clinical practice should possess. The prerequisites listed are: that clinical information not sufficient to meet the disease criteria should be used as effectively as possible, that diseases low in probability but high in seriousness should be considered by clinicians in the differential diagnoses; that diagnosis should be readily changed when necessary; that the component of benefit to the patient should be included in the model; and that the relationship between nosological definition of diseases and practical diagnostic criteria should be explained explicitly. In addition, the author emphasizes that psychiatric diagnosis involves "decision-making under the condition of incomplete information", because most psychiatric diseases are still of unknown etiology. With all these conditions in mind, the author contends that the Bayesian statistical model of decision-making is suited to the frame of reference, and that it should replace the classification model as a guiding principle. This model can integrate various aspects of psychiatric clinical activities systematically and explicitly. A case is presented to illustrate the model in a clinical context. The author points out problems to be solved in current psychiatry from the perspective of the Bayesian model of decision-making. Finally, limitations of the Bayesian model view are discussed. PMID- 11215386 TI - [Retrospective and prospective view of psychiatry in Japan]. PMID- 11215387 TI - [Working plan for the graduate education of psychiatry by committees of Japanese Society of Psychiatry]. PMID- 11215388 TI - [Interdepartmental-rotation training of physicians in Japan--special reference to essentiality of psychiatry training]. PMID- 11215389 TI - [Essentiality of graduate cross training in psychiatry]. PMID- 11215390 TI - [Feasibility of graduate education in community psychiatric hospitals]. PMID- 11215391 TI - [Midterm report on changing terminology of schizophrenia and the international trend]. PMID- 11215392 TI - [Results of patient questionnaires on changing terminology of schizophrenia]. PMID- 11215393 TI - [Clinical professional views on changing terminology of schizophrenia]. PMID- 11215394 TI - [Care management views on changing terminology of schizophrenia]. PMID- 11215395 TI - [Circumstances in changing terminology of mental retardation and the significance]. PMID- 11215396 TI - [Future activities of the Committee for Changing Terminology of Mental Disorders]. PMID- 11215397 TI - [Disruption of prepulse inhibition of acoustic startle as an animal model for schizophrenia]. AB - Disruption of prepulse inhibition (PPI) of acoustic startle in rats has been widely used as an animal model for the sensorimotor gating deficit state usually found in schizophrenia. PPI was reported to be regulated by forebrain circuits, including mesolimbic cortex, nucleus accumbens, ventral pallidum, thalamus, and pedunculopontine tegmentum nucleus. Phencyclidine or dopamine agonists, which causes psychotomimetic symptoms in humans, disrupts PPI in animals. The ED50 value of the drugs to reverse the phencyclidine-induced PPI disruption was significantly correlated with the affinity for the serotonin 2A receptor, but not for the dopamine D2 receptor of each drug (including atypical antipsychotics). In contrast, the ED50 value of the drugs to reverse the apomorphine-induced PPI disruption was significantly correlated with the affinity for the dopamine D2 receptor (including typical antipsychotics). Thus the drug that antagonizes the disruption of PPI caused by PCP or DA agonists would be a candidate for a therapeutic agent for the sensorimotor gating deficit state in schizophrenic patients. Neural mechanisms underlying the disruption of PPI were reviewed. PMID- 11215398 TI - [On the role of glutamate within the locus coeruleus during the development of opioid dependence and on the expression of withdrawal from dependence on opioids]. AB - The development of dependence with repeated use and the expression of withdrawal syndrome are characteristic features of all the opioids represented by morphine. Although many studies regarding several neurotransmitters and receptors have been conducted to define the mechanism involved in the development of dependence on opioids, the definitive evidence has still not been presented. Hyperactivity of noradrenergic neurons within the locus coeruleus has been proposed to play a critical role in the physiological and behavioral responses that comprise opioid withdrawal. Furthermore, much recent interest has been focused on the putative involvement of glutamate within the locus coeruleus, as one member of the excitatory amino acid neurotransmitter family, in the development of dependence on opioids, since several results obtained from a variety of molecular biological, electrophysiological, biochemical, and behavioral studies indicate that glutamate and its receptors participate in both the withdrawal-associated increase in neuronal activity of locus coeruleus and the expression of opioid withdrawal behaviors. Therefore the present review will evaluate a recent trend regarding the role of glutamate within the locus coeruleus during the development of opioid dependence and on the expression of withdrawal from dependence on opioids. PMID- 11215399 TI - [Successful treatment using low-dose carbamazepine for a patient of personality change after mild diffuse brain injury]. AB - A 19-year-old male had a traffic accident while driving his motorbike and suffered an injury to the left frontotemporal part of the head. He remained conscious, had no focal neurological signs, and brain-computed tomography was unremarkable at the prefectural hospital, department of neurosurgery. Six months later he demonstrated a personality change, which was marked by irritability, aggression, labile moods, childishness, irresponsibility, and a lack of motivation. He sometimes made trouble for those around him, and he consulted our hospital 2 years and 9 months after the accident. He was diagnosed as having posttraumatic personality disorder and was treated with clonazepam, a dosage of up to 1.5 mg/day. Although his symptoms were moderately improved, he complained of sleepiness as an adverse effect. Carbamazepine (100 mg/day) was added in expectation of further improvement. Within a few days he improved to his preaccident personality. After the administration of clonazepam was discontinued, he maintained his good mental status. Now about two years after the initiation of therapy, he works in social welfare facilities and has no relapses. Even if a head injury is mild without definite organic signs in brain, it may have a possibility of causing personality change, which may be treatable. PMID- 11215400 TI - [Molecular mechanisms of differentiation and death of human neurons: with special reference to necdin and APP]. AB - To elucidate the mechanisms underlying physiological development and neurodegenerative disorders of the human brain, information about molecular cell biology of human neurons is indispensable. Necdin, which is expressed in postmitotic neurons, binds to viral oncoproteins and the cell-cycle-related transcription factors E2F and p53. Ectopic expression of necdin in proliferative cells suppresses cell division. Necdin is expressed in neurons in phylogenetically old brain areas such as the brain stem and hypothalamus. The human necdin gene, which resides in the chromosome 15q11-q12 region, is not expressed in the Prader-Willi syndrome, suggesting that necdin is responsible for the pathogenesis of this genomic-imprinting-related neurobehavioral disorder. The Alzheimer amyloid precursor protein (APP) is a membrane-bound protein that is abundantly expressed in postmitotic neurons. The proteolytic processing of APP generates A beta, which is deposited in the brains of patients with Alzheimer's disease. APP is strongly expressed in neurons in phylogenetically new brain areas such as human association cortices. When APP is overexpressed in postomitotic neurons differentiated from human embryonal carcinoma by adenovirus-mediated gene transfer, it induces typical apoptosis through caspase-3 activation. Thus APP may be a proapoptotic molecule involved in neuronal death in Alzheimer's disease. PMID- 11215401 TI - [Neuronal cell damage in aceruloplasminemia]. AB - Aceruloplasminemia is a newly recognized autosomal recessive disorder of iron metabolism that causes neurodegeneration of the retina and basal ganglia, as well as diabetes mellitus. The neurological symptoms in affected patients include involuntary movements, ataxia, and dementia reflecting the sites of iron deposition detected by MRI, and the regions of neurodegeneration observed at autopsy. Excess iron functions as a potent catalyst of biologic oxidation. CSF from affected patients revealed a threefold increased iron concentration associated with increased superoxide dismutase activity and lipid peroxidation products. We found that the amount of iron accumulated in various regions of the brain and visceral organs is correlated with the levels of the oxysterols, including 7-hydroxycholesterol, and 7-ketocholesterol, which are directly produced from cholesterol by active oxygen species. Positron emission tomography done on brains of aceruloplasminemia patients showed cortical glucose hypometabolism. Enzyme activities in the mitochondrial respiratory chain of the cerebral cortices of the patients were reduced to approximate 62% and 71%, respectively, for complexes I and IV. These findings suggest that iron-mediated free radicals contribute to lipid peroxidation and the impairment of mitochondrial energy metabolism in aceruloplasminemia. PMID- 11215402 TI - [Corticohistogenesis and Reelin signal cascade]. AB - Corticohistogenesis follows highly regulated spatial and temporal patterns of cell proliferation, neuronal migration and neuronal differentiation to generate the characteristic cortical layers. We gained several insights into the mechanisms of the processes how a class of neurons attains an appropriate layer in developing neocortex. Using a neurological mutant mice reeler, we identified that the extracellular matrix protein Reelin that is specifically secreted from the Cajal-Retzius cells regulates the positioning of the cortical plate neurons. There has identified that Dab1 is one of the intracellular signaling components that respond to Reelin. Recently, three membrane proteins, apoER2, VLDLR and CNR are identified to bind Reelin. The double mutant--apoER2-/-; vldlr-/(-)--shows a phenotype indistinguishable from Reelin deficient mice. The CNRs are originally isolated through the interaction of their intracellular domain with Fyn, a member of the Src kinase family. The antibodies against Reelin or CNR disrupted Reelin CNR binding. These three classes of membrane proteins are thought to act in concert as components of the Reelin receptor. PMID- 11215404 TI - [Treatment of schizophrenia in the acute stage]. PMID- 11215403 TI - [Evolution and update of detoxification techniques for opiate addicts]. PMID- 11215405 TI - [Psychotherapy of delusion]. PMID- 11215406 TI - [Stress coping and cognitive behavior therapy]. PMID- 11215407 TI - [Employment and assistance in independent living]. PMID- 11215408 TI - [Exaggerated expressed emotion, family intervention through psychological education, and drug therapy]. PMID- 11215410 TI - [Regional life support system--practice at "Yadokari no Sato"]. PMID- 11215409 TI - [Activities of the rehabilitation committee and a survey on group workshops]. PMID- 11215411 TI - [Community participation and independence of the mentally handicapped]. PMID- 11215412 TI - [Activities at "Step", a patients' advocacy center and problems in the future]. PMID- 11215413 TI - [Problems related to regional support of patients in daily living]. PMID- 11215414 TI - [The current status of personality disorders in psychiatry]. AB - A growing body of research has elucidated the bio-psycho-social backgrounds and clinical facts of personality disorders defined in DSM-III-IV Axis II, and has endorsed the clinical value of the diagnoses. However, the concept of personality disorder still remains diaphanous, and requires further clarification. One complication is that personality disorder can be seen from either the perspective that is a milder variant of other Axis I disorders, or that it is an abnormally exaggerated form of normal personality traits. That the disorders can be grouped according to these viewpoints indicates that there may be heterogeneity within them, while they have common characteristics: a long duration, extended areas of affected functioning, subtle and marginal severity of symptoms, and "person-near" nature. These features may also account for the difficulty in defining and assessing the disorder. Treatment is another important focus for discussion. Patient-therapist cooperation is essential and of itself is a difficult goal. Most failures of the therapeutic relationship lead to a variety of problems, including legal or ethical ones. Prerequisites for involuntary treatment, remedies for the risk of treatment disruption by violent acting-out and preventing malpractice are issues to be discussed. Inexorably we must return to the principle that our task is to help our patients take ultimate responsibility for decisions about their personality. PMID- 11215415 TI - [On the improvement of everyday life behavior of chronic schizophrenic patients; from the viewpoint of "play-like behavior"]. AB - In this study, the author examined the behavioral patterns of chronic schizophrenic inpatients to follow the process of the amelioration of abulic symptoms such as loss of interest, poverty of thought, lack of sociality, and poor communication. In everyday life in the ward, abulic patients had difficulties in accomplishing not only the basic habitual acts such as getting up or going to bed regularly, exchanging greetings, cleaning teeth, bathing, and washing clothes, but also their assigned duties on the ward. Furthermore, they were unable to behave according to the rules for inpatients, express their emotions appropriately, or build normal interpersonal relationship. The author found that five inpatients achieved some spontaneous behaviors of their own choices in the process of improvement in the above-mentioned habitual acts. As these spontaneous behaviors proceeded through several phases, obvious improvements in their behavioral patterns in everyday life were also observed. The initial phase of transient spontaneous behavior was followed by the second phase of continual spontaneous behavior. Finally, in the interview sessions, the patients became to express pleasurable emotions and physical feelings when they performed their own acts of continual spontaneous behavior. This phenomenon seemed valuable in the therapeutic context because schizophrenic patients are considered seldom capable of having positive feelings toward their own experiences. Therefore, these pleasurable continual spontaneous behaviors may be called "play-like behavior", as confirmed by comparison with the properties of "play" as defined by Caillois. In considering schizophrenic autism, Minkowski described "activite autiste" as an intrinsic quality of the way of life in schizophrenic patients. The manifestation of such quality in spontaneous behaviors can be regarded as having two meanings; an aspect of pathological acting out and a sign of recovery to realistic behaviors. Therapists should consider both aspects when conducting therapies. Although the patients regained the habits and norms of everyday life during hospitalization, the rules involved in "play-like" behavior seemed to contradict some rules in the habitual acts or assigned duties in their daily lives because within "play-like" behavior, freedom predominates over rules. The rules in "play-like" behavior are acquired mostly by mimicking other people. These rules are not fixed laws with penalties but are changeable rules depending on the circumstances of the behavioral process. From this viewpoint, "play-like" behavior allows the patients to acquire practical rules and to understand the relative nature of the rules. Most of the "play-like" behaviors originate from the preferences of the individual patients, which may be something that they have already experienced, something that they have longed for, or something that gives them self-fulfillment. These qualities contribute to the acquisition of experiences that they find pleasurable. For the patients, recalling each "play-like" behavior in the interview sessions enables them to grasp the whole picture of their behaviors, to reinforce their attachment to these behaviors as their own experiences, and to promote the dynamic process between behavior and thought. In this sense, psychotherapy incorporating the aspect of "play-like" behavior seems to prepare the schizophrenic patients to improve their way of thinking. To nurture "play-like" behavior helps the chronic schizophrenic patients to recover will power, independence and sociality, and contributes to the improvement of clinical symptoms and of daily life activities. PMID- 11215416 TI - [A patient with hemorrhage originating from an unknown coagulation pathway inhibitor]. AB - The hemorrhagic disorders associated with circulating anticoagulant are rare but well known as the disease derived from inhibitors(alloantibody or autoantibody), which arise against specific coagulation factors. We encountered a patient with hemorrhage at the lower limbs originating from an unknown coagulation pathway inhibitor. Activated partial thromboplastin time(APTT) prolonged and cross mixing test indicated a coagulation pathway inhibitor. Levels of coagulation factors VIII, IX, XI, and XII were extremely low. Predonine therapy was effective to stop the hemorrhage. To clarify the inhibitor, we treated the patient's plasma with protein A Sepharose, and the factor VIII activity was recovered to a normal level after passing through the column. Gel filtration of the patient's plasma and protein A Sepharose adsorbed fraction of the patient's plasma with Superdex 200 revealed that the inhibitor activity against blood coagulation eluted at the position of IgG, which was detected by the prolongation of APTT of normal pooled plasma. These data indicated that the inhibitor was IgG and its inhibitory spectrum was non-specific and broad. The results of laboratory tests and the clinical features in our patient were similar to those in a previous study by Dahlback(Blood 62, 218-225, 1983). The hemorrhagic abnormality of that patient was derived from the autoantibody to phospholipid, which inhibits the activation of prothrombin. An investigation into the effect of anti-phospholipid antibody in our patient is currently being performed in our laboratory. PMID- 11215417 TI - [Clinical cases of acquired coagulation inhibitors]. AB - The acquired coagulation factor inhibitors are classified into alloantibodies, which appear in association with supplementary treatment for congenital coagulation factor deficiency, and autoantibodies, which are spontaneously produced. We report here 2 cases of acquired factor VIII inhibitor and 1 case of factor V inhibitor. Case 1: A 52-year-old woman noted swelling of the right parotid region in March 1988. Though contrast examination was scheduled, she was admitted for detailed examination due to a markedly prolonged coagulation time. An APTT correction test suggested that decreased factor VIII activity was due to the presence of an inhibitor. Since antinuclear antibody and SS-A antibody were positive and infiltration by lymphocytes in the salivary gland acini in a lip biopsy specimen was detected, Sjogren's syndrome was diagnosed. Case 2: A 33-year old woman had normal delivery of her second child in February 1998. In June 1998, she suffered slight contusion in the left lower limb. The affected site became swollen and painful, making walking difficult. Since both upper limbs became markedly swollen after 1 week, she visited our hospital. Prolonged APTT and a marked decrease in factor VIII activity were observed. Factor VIII inhibitor titer was high at 19 Bethesda units. Case 3: A 64-year-old man had had asymptomatic macroscopic hematuria since the beginning of August 1998 but was placed under observation since no abnormal findings were observed on various imaging tests. However, he was admitted to Osaka City General Medical Center because of vesicular tamponade. Factor V activity was markedly decreased to 1.0%. PT correction test suggested that decreased factor V activity was due to the presence of an inhibitor. The underlying disease could not be determined in this case. In patients with acquired coagulation inhibitors, bleeding symptoms are reported to be mild in many cases, and severe bleeding is rare. However, cases of death without severe bleeding or underlying disease have also been reported, indicating that the prompt diagnosis and treatment of this condition are necessary. PMID- 11215418 TI - [Clinical data obtained through coagulation testing suggests that hypothermia exerts influence on a patient's blood coagulation reaction]. AB - It often takes longer to achieve hemostasis when performing an operation on a patient in cerebral hypothermia therapy than in a normal patient, despite the lack of abnormal clinical blood coagulation findings, and this study was conducted to investigate the cause of delays in coagulation in patients with hypothermia. In this study, 93 samples of plasma were collected at our center from 10 patients(7 men and 3 women; mean age, 33.7) who were in cerebral hypothermia therapy with a urinary bladder temperature maintained at 32-34 degrees C. Each sample was divided into two, and PT(prothrombin time) and APTT(activated partial thromboplastin time) were measured at the normal analysis temperature of 37 degrees C in one sample, and at the hypothermia temperature of 32-34 degrees C in the other sample. The results showed that PT and APTT tended to shorter at 37 degrees C, than those measured at 32-34 degrees C. Thus, we suggest that it is necessary to regulate the temperature of patients with accidental hypothermia or in whom hypothermia therapy is performed. PMID- 11215419 TI - [The examinations for diffuse lung diseases]. AB - Diffuse lung diseases show an abnormal shadow that is widely scattered on the bilateral lung fields in the chest X ray view and includes many respiratory diseases such as the infectious or the non-infectious disease; neoplasms. Among these, idiopathic pulmonary fibrosis(IPF) has been studied extensively because of its high frequency and difficulty of treatment. IPF is defined by the respiratory functions, the radiological findings, which depend on HRCT, and the histopathological evaluation by surgical lung biopsy. In particular, the histopathological appearance of usual interstitial pneumonia(UIP) is essential for the diagnosis of IPF. Most serum examinations such as angiotensin-converting enzyme, anti-nuclear antibodies are applied to rule out other diffuse lung diseases. SP-D or KL-6, which is the marker of the type II epithelial cells, is thought to be very useful for revealing the disease activity, but since it is not increased in the early stages of IPF, it is not applied in the diagnosis of IPF. The definitive serum examinations for the diagnosis or determinations of the therapeutic effect or prognosis of IPF have not been established. Easier, more useful and critical examinations including genetic diagnosis are required to manage patients with IPF. PMID- 11215420 TI - [Clinical examinations for COPD]. AB - The natural history of COPD such as pulmonary emphysema demonstrates that FEV1 rapidly declines in smokers who are susceptible to cigarette smoke. The susceptible smokers who quit smoking do not regain only a little, but the rate of the FEV1 decline is no longer steep. These have been interpreted that early detection of this obstructive impairment is the most important issue to prevent the progression to severe emphysema. Pulmonary function tests, at least a measure of FEV1, in the all middle-aged smokers have been particularly recommended. The smokers with abnormal FEV1 defect should be advised to quit smoking. In moderate and severe cases, after staging of the disease by pulmonary function and exercise tests, assessments of complicated factors such as eosinophilic bronchitis are clinically important for constructing therapeutic strategies. Asthmatic component can be assessed by eosinophil count in the sputum and/or reversibility of the pulmonary function after challenging of bronchodilater inhalations. In the severe stage of the disease, examinations such as arterial blood gas analysis and pulse oxymetric measure are critical because oxygen therapy for the patients with respiratory failure has been known to improve survival prognosis. Portable devices which can assess arterial oxygen saturation during daily activity will be useful to decide its indication or to titrate oxygen. In conclusion, clinical examination in COPD, particularly in pulmonary emphysema in this paper, should appropriately be planned in each stage of the disease, or in each clinical purpose. PMID- 11215421 TI - [Tests for bronchial asthma]. AB - One characteristic feature of bronchial asthma is an allergic inflammation of the airways involving eosinophil activation. Since adhesion molecules, cytokines, and chemokines play a critical role in eosinophil infiltration into the tissues, it is of paramount importance to utilize these inflammation-related factors as clinical parameters to assess the status of asthma. For this reason, we measured the level of RANTES and soluble ICAM-1 in patients with asthma. The concentration of plasma RANTES was significantly elevated in asthmatic patients as compared with normal subjects. Patients with asthma attacks exhibited higher RANTES levels than those in remission. sICAM-1 concentration was also higher in serum and sputum in patients with asthma than in healthy subjects. In order to detect eosinophil activation directly, we studied intracellular EG2 expression in eosinophils using whole-blood flow-cytometric analysis. The number of EG2 positive eosinophils was significantly greater in patients with attacks than in asymptomatic subjects. We measured the temperature of expiratory flow and temperature flux as an alternative approach to assess airway inflammation. This study was based on a concept that inflammation would produce heat resulting in the higher temperature. The coefficient of temperature flux was significantly greater in asthmatic patients than in normal controls. Therefore, these new tests may be useful for the evaluation and treatment of allergic inflammation in asthma. PMID- 11215422 TI - [Recent progress in the diagnosis of respiratory disease: respiratory infection]. AB - In Japan, molecular diagnostic techniques and some other diagnostic tools for respiratory infections have been clinically introduced and their use has spread in recent years. In particular, PCR is now commonly used even at the clinical microbiology laboratory level, because PCR based direct detection of infectious disease from various clinical specimens has some advantages over other diagnostic methods. Since PCR is a highly sensitive, specific, rapid method and suitable for slow-growing or culture-difficult pathogens, we must take care in regard to the risk of contamination, the possibility of false-negative results by various PCR inhibitors in the clinical sample, or unstable sensitivity easily influenced by the quality of samples and DNA extraction step. PMID- 11215423 TI - [Clinical examinations on lung cancer]. AB - The incidence of lung cancer is increasing in Japan and it is important to know whether a patient has a history of primary smoking/second-hand smoking because smoking is the main cause of lung cancer. Lung cancer is often found on chest roentgenography. In order to determine the strategy of the treatment, the stage of the disease can be studied by the examinations of morphology(chest computed tomography), pathology(biopsy under bronchoscopy) and biochemistry(tumor markers and genetic analysis). Most lung cancers are detected in the advanced stage with metastasis. Performance status should be useful for the estimation of the prognosis of patients. In the symposium, we reported two of our clinical cases, in which urinary deoxypyridinoline, a bone absorption marker, facilitated the discovery of the bone metastasis of lung cancers with negative bone scans. We were requested to verify the early diagnosis of lung cancers with a collection of data on morphology, pathology and biochemistry. PMID- 11215425 TI - [Practice and application of evidence-based medicine]. AB - Evidence-based medicine is an approach to clinical practice that aims to solve the patient's problems. EBM includes five steps: identifying patient's problems, searching medical literature efficiently, critically appraising the literature(evidence), applying it to patient care, and self-assessment of these steps. Since September 1999, we have practiced the EBM approach to patient care, in inpatient and outpatient settings at the department of General Medicine of Saga Medical School. We found ourselves more clearly differentiating between the EBM approach and past conventional practice. We found EBM to be more clinically useful and we have enjoyed reading medical literature because of the focus on patient's problems. To improve our use of the EBM approach, we need to study more about clinical epidemiology to evaluate and use medical literature in patient care. PMID- 11215424 TI - [Introducing EBM for postgraduate training]. AB - The introduction of Evidence-based medicine(EBM) for residency training is recommended by the Japanese Society of Internal Medicine. At our hospital, we put the emphasis on learning vital clinical epidemiology through clinical experience. When educating EBM to our residents, we especially focus on the diagnostic process, because the knowledge of clinical epidemiology is useful while making the diagnosis and evaluating the diagnostic hypothesis. In our daily conference among residents and medical educators, the logic of clinical epidemiology is used for evaluating the validity of clinical judgment on diagnosis. We suggest three components upon making a diagnosis: 1. Always suspect a particular disease when ordering a laboratory test 2. Know the sensitivity and specificity of the test 3. Apply the test result in order to reevaluate the pretest hypothesis In this article, interaction among staff and residents are presented and discussed with these components in our minds. By repeating these interactions, the residents will be able to understand the importance of EBM and will be able to apply it in the clinical practice. PMID- 11215426 TI - [Nosocomial infection monitoring system featuring detection of local clustering]. AB - We have developed a nosocomial infection surveillance system making use of data from laboratory information system. The system makes cross-reference table of detected bacteria according to either the site of occurrence(hospital wards) or antibiotic sensitivity. It is capable of listing all the patients or serial changes in frequency for any specified bacterium. Furthermore, we have developed an algorism to detect local clustering. For each ward, the system calculates all combinations of distance between beds of patients with specified bacteria. We named the statistics as DC(degree of cluster) and its significance was judged by a confidence interval of DC obtained by a bootstrap method by randomly assigning the same number of patients to the beds in the same wards. Retrospective analysis of the distribution of 4 major bacteria in the wards proved that DC is a sensitive indicator of local clustering. PMID- 11215427 TI - [Homogenous low-density lipoprotein assay in type III hyperlipoproteinemia]. AB - To investigate whether homogenous analysis of serum low-density lipoprotein cholesterol(LDL-C) was applicable in type III hyperlipoproteinemic subjects, 3 reagents were used to estimate LDL-C in 2 cases with apoE 2/2 phenotype. Each measurements were compared to LDL-C levels by ultracentrifugation(density: 1.019 1.063). LDL-C levels by homogenous analysis with any of the reagents were higher than those by ultracentrifugation, and the difference was varied between the reagents: +14-24% by LDL-EX, +29-55% by Cholestest LDL, and +89-115% by Determiner LDL-C. The cross-reaction by the reagents to intermediate density lipoprotein(IDL) and very low density lipoprotein(VLDL) cholesterol was studied in a case; 22% of cholesterol in these fractions was measured by LDL-EX, 32% by Cholestest LDL, and 110% by Determiner LDL-C. A part of the sample serum was stored at -60 degrees C for several days and melted for re-analysis of homogenous LDL-C levels. After the freezing process, IDL fraction pattern on electrophoresis had been changed and homogenous LDL-C levels by all reagents were different from the measurements of native serum. These results indicated that using reagents with low cross-reaction to IDL and VLDL fractions and careful sample handling are important in homogenous LDL-C analysis in type III hyperlipoproteinemia. PMID- 11215428 TI - [Clinical utility of transcription mediated amplification-hybridization protection method(TMA-HPA) for the detection of HBV DNA: a comparison with the branched DNA probe assay]. AB - The clinical utility of the TMA-HPA method for the detection of HBV DNA was evaluated by comparing results with the branched DNA probe(b-DNA) assay. Sera from 135 biopsy-confirmed HBV carriers were included in the study. Dilution tests with two representative sera revealed the sensitivity of the TMA-HPA method to be 100-fold higher than that of the b-DNA assay. Among the 135 test sera, HBV DNA measurements obtained by the two assays showed a high degree of correlation(r = 0.861, p < 0.0001). Of the 72 sera which tested positive for HBe antigen, 71 and 67 were positive for HBV DNA when tested by TMA-HPA and b-DNA assay, respectively. In contrast, of the 63 which tested negative for HBe antigen, 42 were positive for HBV DNA when tested by TMA-HPA, and only 19 were positive when tested by b-DNA assay(p < 0.05). Among HBe antigen-positive HBV carriers, HBV DNA levels as determined both TMA-HPA and b-DNA assay showed an inverse relationship with pathological stage, but among HBe antigen-negative HBV carriers, no such tendency was observed. Based on these results, it is felt that the detection of HBV DNA by TMA-HPA is useful for the evaluating anti-viral therapeutic effect in HBV carriers, and in estimating a prognosis. PMID- 11215429 TI - [Anesthesiology in the new century]. PMID- 11215430 TI - [Perioperative care for transplantation recipients(discussion)]. PMID- 11215431 TI - [Physiological monitoring in the new century(discussion)]. PMID- 11215432 TI - [Body temperature control in Perioperative period]. PMID- 11215433 TI - [Blood coagulation disorders and anesthesia]. PMID- 11215434 TI - [Basic and clinical studies on chronic pain and the diagnosis with drug challenge test]. PMID- 11215435 TI - [Anesthetic management in great vessel operations]. PMID- 11215436 TI - [Knowledge of drug interactions necessary to anesthetic managements]. PMID- 11215437 TI - [Management of postoperative pain in pediatrics]. PMID- 11215438 TI - [Perioperative care for surgical patients with endocrine disorders]. PMID- 11215439 TI - [Evaluation of intraoperative tissue ischemia and the anesthetic management]. PMID- 11215440 TI - [Opioid and pruritus]. PMID- 11215441 TI - [Postoperative central nervous system disorders and the management]. PMID- 11215442 TI - [Perioperative anesthetic management for surgical patients with respiration disorders]. PMID- 11215443 TI - [Role of vasoconstrictor agents in anesthesiology and the effects on other physiological functions]. PMID- 11215444 TI - [Introduction of bupivacaine as spinal anesthetic agents]. PMID- 11215445 TI - [Balanced anesthesia in the 21st century(discussion)]. PMID- 11215446 TI - [Recent studies in anesthesiology--special reference to respiration(discussion)]. PMID- 11215448 TI - [Medical treatment and medicine in the 21st century: medicine and human beings]. PMID- 11215447 TI - [Women physicians and anesthesiology(discussion)]. PMID- 11215449 TI - [Analgesic management in the new century--special reference to opioids, NSAIDs, and local anesthetics(discussion)]. PMID- 11215450 TI - [Retrospect of anesthesiology in last century and prospects on the future(discussion)]. PMID- 11215451 TI - [Emergency medicine in the new century(discussion)]. PMID- 11215452 TI - [Various tasks suggested for intensive care in the new century(discussion)]. PMID- 11215453 TI - [Recent progress on studies of anesthesiology--cardiovascular circulation(discussion)]. PMID- 11215454 TI - [Epidural anesthesia and spinal anesthesia in the new century(discussion)]. PMID- 11215456 TI - [Liver transplantation in Japan]. PMID- 11215455 TI - [Perioperative care for surgical patients with respiratory tract disease- preparation of the guideline(discussion)]. PMID- 11215457 TI - [Expectation on liver transplantation: discussion]. PMID- 11215458 TI - [Multicentric Castleman's disease with reversible left ventricular diffuse hypokinesis]. PMID- 11215459 TI - [Adult T-cell leukemia/lymphoma following Sjogren's syndrome]. PMID- 11215460 TI - [Multiple cystic adenocarcinoma of the lung]. PMID- 11215461 TI - [Non-producer Multiple myeloma]. PMID- 11215462 TI - [Aortic valve infective endocarditis due to Campylobacter fetus]. PMID- 11215463 TI - [Drug-induced pulmonary diseases and clinical practice]. PMID- 11215464 TI - [Mechanism of the development of fibrosis in dermal and visceral sclerosis]. PMID- 11215465 TI - ["Domino" transplantation]. PMID- 11215466 TI - [Collagen diseases and multiple drug resistance genes]. PMID- 11215467 TI - [Liver transplantation from brain dead patients]. PMID- 11215468 TI - [Primary sclerosing cholangitis]. PMID- 11215469 TI - [Primary biliary cirrhosis]. PMID- 11215470 TI - [Disease conditions and indications for liver transplantation]. PMID- 11215471 TI - [Metabolic liver diseases]. PMID- 11215472 TI - [Type B liver cirrhosis]. PMID- 11215473 TI - [Type C liver cirrhosis]. PMID- 11215474 TI - [Liver transplantation in fulminant hepatitis--from the viewpoint of a transplantation specialist]. PMID- 11215475 TI - [Liver cancer]. PMID- 11215476 TI - [Pathology of liver transplantation]. PMID- 11215477 TI - [Postoperative care and complications]. PMID- 11215478 TI - [Partial liver transplantation from living donors]. PMID- 11215479 TI - [Artificial liver]. PMID- 11215480 TI - [Blood group genes]. AB - Blood group antigens are surface markers on the red blood cell membrane. Biochemical analysis of blood group antigens has shown that these antigens divide into two types of proteins and carbohydrates attached to lipids or proteins. Protein determinants are directly coded on blood group genes, while carbohydrate determinants are controlled through the expression of glycosyltransferase enzymes. For the past ten years, considerable information has been gained from molecular studies of many blood group systems, thereby clarifying several aspects of these genes, genetic backgrounds of variants, and molecular evolution. Additionally, it has become possible to genotype blood groups and to genetically engineer the expression of protein antigens and the activity and specificity of enzymes. ABO system on the carbohydrate and Rh system on the protein are the most important systems in transfusion medicine. In this paper, we will review recent progress in the field of blood grouping; mainly ABO and Rh. PMID- 11215481 TI - [Neuroimaging and electrophysiological study in epilepsy]. AB - There exist various morphological and biochemical changes closely associated with electrophysiological phenomena which cause epileptic seizures in the brains of epilepsy patients. Recent developments in investigation methods, not only electrophysiological(EEG and MEG), but also neuroimaging involving morphological imaging(CT and conventional MRI) and functional imaging(SPECT, PET, functional MRI and MRS) is able to demonstrate these changes. SPECT and PET can particularly clarify the changes of cerebral blood flow and glucose metabolism between interictal and ictal periods. In our experience of 423 patients who underwent epilepsy surgery for intractable seizures, these interventions provide important information to identify the epileptogenic foci. However, in practice, discordance in the results of these presurgical evaluations is recognized, and invasive intracranial recordings are needed in such cases. These problems in diagnosis were shown especially in patients with mesial temporal sclerosis and focal cortical dysplasia. To detect an epileptogenic focus more clearly, a combination of morphological and functional findings, new functional imaging such as neurotransmitter receptor imaging, EEG-triggered or neuropharmacological functional MRI, as well as, statistical parametric analysis may be needed. PMID- 11215482 TI - [Clinical significance of serum LpA-I levels measured by immunoturbidimetric assay in type 2 diabetes mellitus patients]. AB - Previously, we developed an immunoturbidimetric assay method for lipoprotein A I(LpA-I) on sera pre-absorbed with anti-apolipoprotein A-II. In the present study, correlations between serum lipoprotein A-I and other serum parameters levels were examined and LpA-I levels were studied in patients with type 2 diabetes mellitus. The serum levels of LpA-I did not correlate with those of diabetic markers such as fasted blood glucose, glycohemoglobin(HbA1c) and fructosamine, but correlated well with the levels of total cholesterol and HDL cholesterol, phospholipids, apolipoprotein A-I and seemed to correlate inversely with arteriosclerosis index. In patients with type 2 diabetes mellitus, LpA-I levels were significantly lower than those in normal subjects. Especially, LpA-I levels of patients with diabetic complications were significantly lower than those in normal subjects and non-complicated diabetic patients. Then, the measurement of LpA-I levels in patients with type 2 diabetes mellitus was considered to be useful for prevention and management of arteriosclerosis. PMID- 11215483 TI - [The ratios of apoC-III/apoC-II in normal full-term maternal bloods and their umbilical cord bloods]. AB - In this paper, serum concentrations of CII and CIII in MB(n = 12) represented 158% and 237% of those in 20 specimens of normolipidemic venous blood from healthy fasting non-pregnant females(Control), and the CIII/CII ratio of MB(mean +/- SD = 3.6 +/- 0.4) was significantly higher than that of the Control(2.38 +/- 0.42). While the difference between the serum CII level in MB and that of 14 specimens of postmenopausal patients lipid-matched to MB(postM HL) was not significant, serum CIII concentration of MB was significantly higher than that of postM HL. Furthermore, while the difference between the CIII level in apoB containing lipoproteins of MB and that of postM HL was not significant, the CIII concentration in HDL(HDL-CIII) of MB was significantly higher than that of postM HL. It was suggested that the effect of pregnancy on apoC levels which change in parallel with the TGs level might reflect the selective increase in HDL-CIII concentration. In addition, the positive correlation between HDL-CIII and apoA-I concentration in MB was significant. However, it has been reported that the CIII/CII ratio of patients with type III hyperlipidemia treated with estrogens had been successively increased, and it was also reported that estrogens stimulate the synthesis of CIII in hepatocytes. It was thus suggested that maternal CIII as well as apoA-I might be selectively overproduced in the liver by stimulation from increased endogenous estrogens during normal pregnancy. On the contrary, the serum concentrations of CII and CIII in UCB represented 71% and 55% of those in Control, and the CIII/CII ratio of UCB(1.87 +/- 0.5) was significantly lower than those of the Control. In UCB, the positive correlation between CIII and TGs was weak(p < 0.1) and CII did not correlate with markedly decreased TGs. Serum concentrations of CII, CIII and the ratio of CIII/CII in MB did not correlate with those in UCB, respectively. Moreover, birth weight and birth length of neonates positively correlated with concentrations of TGs, CII and CIII in MB, respectively, but not in UCB. In conclusion, the increased maternal CIII/CII ratio is due to the estrogen-induced raise of CIII while the reduced neonatal CIII/CII is related to the decrease in TGs. These observations suggest that fetal TGs-rich lipoprotein metabolism is not affected by maternal lipoprotein metabolism. PMID- 11215484 TI - [Development for the determination of band 5b tartrate-resistant acid phosphatase activity in serum]. AB - Band 5 Tartrate-resistant acid phosphatase(TRACP; EC 3.1.3.2) consists of two isoenzymes, bands 5a and 5b, of which band 5b TRACP, an enzyme expressed in bone resorbing osteoclasts, is secreted into the circulation during bone resorption. Band 5b TRACP was measured kinetically in serum as tartrate-resistant fluoride sensitive heparin-resistant ACP with 2,6-dichloro-4-acetylphenyl phosphate as substrate at pH6.6. The within-run(n = 20) and between-run(n = 20) CVs of band 5b TRACP activity were 3.3-5.8% and 5.0-7.3%, respectively. The reference range of band 5b TRACP activity in males(n = 72) and females(n = 87) 20-39 years of age by this method were 3.7-12.5 U/l and 2.7-9.9 U/l, respectively. The band 5b TRACP value was significantly higher in post-menopausal women compared with the menstruating women. The relationship of band 5b TRACP and ultrasound findings in healthy women aged 31-75 years(n = 139) were inversely correlated with stiffness(r = -0.401), speed of sound(SOS; r = -0.386) and broadband ultrasound attenuation(BUA; r = -0.338). These results suggest that band 5b TRACP may be a useful in the evaluation of bone turnover. PMID- 11215485 TI - [Assay for determination of the serum procalcitonin level: biochemical and clinical evaluation]. AB - In patients with inflammatory conditions such as infection, cytokines induce the production of C-reactive protein(CRP) and serum amyloid A protein(SAA) in hepatic cells. It has been reported that upon viral infection, the serum SAA level increases by a greater degree than the serum CRP level. Procalcitonin (PCT), the precursor of calcitonin, is a new type of inflammatory marker that is specifically induced by bacterial infection, sepsis and lethal multiple organ failure, but not by viral infection, autoimmune diseases, tumors or surgical stress. To evaluate the immunoluminometric assay(LUMI test PCT; Brahms Diagnostics, Berlin, Germany) procedure for determining the PCT level and to study the clinical significance of the serum PCT level, we determined the serum levels of PCT, CRP and SAA in patients with various inflammatory diseases and normal subjects. The serum PCT level in the normal subjects was < 0.3 ng/ml. Among the patients with inflammatory disease who had a high CRP level(CRP > 20000 micrograms/dl), the PCT level was elevated only in those patients with severe bacterial infection. These results suggest that determining the PCT level may be useful in the differential diagnosis of severe bacterial infection. The patients who had a low CRP level(CRP < 150 micrograms/dl), had a PCT level within the normal range. The patients with autoimmune disease, viral infection, and fungal infection did not have an elevated PCT level. PMID- 11215486 TI - [Decreased growth hormone secreting cells of the hypophysis in senile cachexia]. AB - Basic morphometry of the pituitary gland in aged patients with cachexia was performed. In 10 control specimens, growth hormone(GH) cells accounted for 42.9 +/- 3.4% of the total, compared with 33.8 +/- 7.0%(p < or = 0.01) in patients with severe cachexia senilis. ACTH cells accounted for 16.0 +/- 7.4% in the control group and 14.1 +/- 9.0% in the senile cachexia group(p > or = 0.1). The mean pituitary weight was 0.60 g in control cases and 0.46 g in cases of extreme cachexia(p < or = 0.01). In the hypophyses of patients with senile cachexia, atrophy of GH cells and increase of the fibrous stroma were also prominent. The ratio of the summarized value for total GH cells in cachexia senilis patients and controls was 1:2.2. The difference was regarded as sufficiently large to be a causative factor in the establishment of cachexia senilis. PMID- 11215487 TI - [Pathological, cytological and immunohistochemical study of normal-sized ovary carcinoma syndrome]. AB - Normal-sized ovary carcinoma syndrome(NOCS) is characterized by diffuse metastatic malignant disease of the abdominal cavity in females, with normal sized ovaries, and no origin assigned definitively by intraoperative evaluation. To elucidate the characteristics of NOCS arising from ovarian carcinoma, we investigated the immunohistochemical reactivities of keratin, epithelial membrane antigen(EMA), vimentin, and proliferative cell nuclear antigen(PCNA) in 4 cases of ovarian carcinoma with NOCS(NOCS group), including 3 cases of serous surface papillary adenocarcinoma(SSPC) and 1 case of small ovarian primary serous papillary adenocarcinoma(SPC). These cases were compared with 3 cases of ovarian carcinoma without NOCS(non-NOCS group), including 3 cases of SPC. Cytological and histological testing of the NOCS and non-NOCS groups showed the same findings. Similar reactivities for keratin, EMA and vimentin were observed in the NOCS and non-NOCS groups. No significant change of PCNA labeling index between the groups was seen. However, clinical stage of the NOCS group was higher than that of non NOCS group. It was hypothesized that exposure of cancer cells to peritoneal cavity in ovarian SSPC leads to the spread. In NOCS case arising from small-sized ovarian carcinoma, another factor was thought to be involved, such as genetic alteration, but it is not known. PMID- 11215488 TI - [Analysis of unusual late responses of peripheral nerves]. AB - F-waves are routinely evaluated in nerve conduction studies on proximal peripheral nerves. However, unusual late responses other than F-waves that show variation in latency and configuration sometimes confound evaluation of the F waves. The unusual late responses were analyzed in this study. In two patients with cervical radiculopathy, two patients with brachial plexus injury and 9 patients with polyneuropathy, A-waves showing constant latency and configuration were recorded in addition to temporally dispersed F-waves. The A-waves in these patients persisted after supramaximal stimulation of the peripheral nerves, although the A-waves should normally disappear in response to supramaximal stimulation. The supramaximally stimulated A-waves were prominent in polyneuropathy and nerve lesions with demyelinating pathology. A patient with Guillain-Barre syndrome showed unusual repetitive discharges that might be important electrodiagnostic findings in the early stage of illness. In patients with myotonic dystrophy, electrical stimulation elicited repetitive discharges that continued from the M-waves. Recordings with a concentric needle electrode showed characteristics similar to those of myotonic discharges recorded during needle electrode insertion. When the repetitive discharges were mild, the F-waves were recorded. Absence of the F-waves in myotonic dystrophy might be related to the myotonic discharges elicited by electrical stimulation, and may not imply impaired conduction of the peripheral nerves. A patient with myokymia showed repetitive discharges with constant configuration but variable latency, although the F-waves were normal. These repetitive discharges may be evoked by ephaptic transmission resulting from abnormal excitability of the peripheral nerves or muscles of different etiologies. PMID- 11215489 TI - [An autopsy case of primary aortoduodenal fistula complicated by both gastric carcinoma and acute gastric mucosal lesions]. AB - We present an autopsy case of aortoduodenal fistula complicated by both gastric carcinoma and acute gastric mucosal lesions(AGML). A 73-year-old man with a past history of gastric ulcer, myocardial infarction, and arteriosclerosis of the right femoral artery presented to Osaka National Hospital complaining of intermittent claudication of the right lower extremity. After a diagnosis of arteriosclerosis obliterans, percutaneous angioplasty was performed. The postoperative course was initially good. However, two weeks after the angioplasty procedure he suddenly vomited blood. Emergency endoscopy revealed both polypoid gastric carcinoma and AGML, which were considered to be the major cause of his gastrointestinal bleeding. And he died of uncontrollable gastrointestinal bleeding two weeks after this examination. Autopsy showed an atherosclerotic aneurysm of the abdominal aorta that had ruptured into the third part of the duodenum. To our knowledge, there has been no previous autopsy on a primary aortoduodenal fistula from an atherosclerotic abdominal aneurysm complicated by similar hemorrhagic gastric lesions. This case emphasizes the difficulty of making a clinical diagnosis of primary aortoduodenal fistula. PMID- 11215490 TI - [A case of hookworm infestation with dissociation values between FDP-E and FDP-D dimer]. AB - We previously reported a five-year-old girl showing bleeding tendency and transient morphological and functional platelet abnormalities probably due to a hookworm, Necator Americanus, infestation. In this report, we describe the rarely accelerated fibrinogenolysis and/or fibrinolysis in this patient whose value of fibrinogen and/or fibrin degradation products(FDP) determined with an FDP-E assay was much higher than that determined with a D-dimer assay. Namely, on day-1 and day-13 of hospitalization, her D-dimer values were only 10 to 20% of the prospected values from FDP-E values. We speculated this phenomenon was induced by circulating protease(-like) agent(s) produced by hookworm, because the only slightly participation of plasmin and/or granulocyte elastase was evaluated by the determination of enzyme-inhibitor complexes. And the other possibility of fibrinogen degradation by blast- or tumor-associated protease was excluded by the clinical manifestations and primary disorders. In conclusion, we report a very rare case with the accelerated fibrinogenolysis and/or fibrinolysis in a patient with the hookworm infestation. We are interested in the mechanism that manifested the patient's bleeding tendency accompanied with morphological and functional platelet abnormalities. PMID- 11215491 TI - [Molecular biology techniques as clinical laboratory tests]. AB - The quality of results obtained with molecular biology techniques depends on the control of preanalytical and analytical error associated with such techniques. Preanalytical error can be introduced during the isolation of DNA and RNA. The type of detergent used in cell lysis can affect the amplification of DNA by techniques such as the polymerase chain reaction(PCR). Ribonuclease(RNase) contamination is a serious problem in the isolation of undegraded RNA, and, thus, this enzyme should be inhibited. Anticoagulants used for blood collection can affect the quality of results with molecular biology techniques. The control of contamination from the working environment is essential to the minimization of preanalytical, analytical and postanalytical error. Molecular biology techniques for a wide range of clinical laboratory tests have been established in hospitals such as clinical laboratory tests for infections, molecular diagnoses of leukemia and aberrant genes in metabolism. PMID- 11215492 TI - Efficacy of polyvinylpolypyrrolidone in reducing the immunotoxicity of aflatoxin in growing broilers. AB - 1. Protective action of an enzyme-linked polyvinylpolypyrrolidone (PVPP, Mycofix Plus) against the immunosuppressive effect of afatoxins (AF) was evaluated by determination of peripheral blood T-lymphocyte proportions and splenic plasma cell counts. Histological changes in lymphoid organs were also investigated by light microscopy. One-d-old broiler chicks (Hybro) received 2.5 mg/kg diet AF (83.06% AFB1, 12.98% AFB2, 2.84% AFG1, 1.12% AFG2) with or without PVPP (3g/kg diet) until 21 d of age. When compared with controls, AF treatment significantly decreased peripheral T-lymphocyte counts. AF caused a slight decrease in splenic plasma cell counts. The addition of PVPP to an AF-containing diet significantly increased T-lymphocyte counts. Splenic plasma cell counts were numerically intermediate between control and AF groups. 3. The dietary addition of PVPP to AF-free diet did not significantly alter either T-lymphocyte or splenic plasma cell counts. PMID- 11215493 TI - A novel anti-HBeAg homolignan, taiwanschirin D from Kadsura matsudai. AB - A novel C19 homolignan, taiwanschirin D (1), possessing a 3,4-(1-[(Z)-2-methoxy-2 oxoethylidenel)pentano (2,3-dihydrobenzo[b]furan)-3(2-oxoacetate) skeleton, was isolated from the stem of Kadsura matsudai Hayata. Its structure was determined from physical and spectral data including 2D NMR spectra. The Anti-HBeAg test revealed that taiwanschirin D (1) had moderate activity at a concentration of 94.3 microM (50 microg/ml). PMID- 11215494 TI - [Environmental pollution with endocrine disrupting chemicals and the effects to human] . PMID- 11215495 TI - Invertases and life beyond sucrose cleavage. PMID- 11215496 TI - New mutants provide clues into regulation of systemic acquired resistance. PMID- 11215498 TI - Bibliography. Current world literature. PMID- 11215497 TI - Systemic transport of RNA in plants. PMID- 11215499 TI - Information and communication. PMID- 11215500 TI - Stress resistance, heterogeneity, and mortality plateaus: a comment on Drapeau et al. PMID- 11215501 TI - Meeting report: first conference of the EU-supported Thematic Network on Immunology and Ageing in Europe (ImAginE), Schloss Hohentubingen, April, 2000. PMID- 11215502 TI - ImAginE: Immunology and Ageing in Europe--a thematic network of the EU 5th Framework Program. PMID- 11215503 TI - Venture capital. Big biz bets on... . PMID- 11215504 TI - Information technology. rapid hire. PMID- 11215505 TI - Disciplining abusive docs. PMID- 11215506 TI - 2001 benchmarking guide. AB - Our fifth annual guide to benchmarking under managed care presents data that is a study in market dynamics and adaptation. New this year are financial indicators on HMOs exiting the market and those remaining. Hospital financial ratios and details on department performance are included. The physician group practice numbers show why physicians are scrutinizing capitated payments. Overall, hospitals in markets with high managed care penetration are more successful in managing labor costs and show productivity gains in imaging services, physical therapy and materials management. PMID- 11215507 TI - The honorary enzyme haemoglobin turns out to be a real enzyme. PMID- 11215508 TI - Introduction: the selenium conundrum. AB - Selenium was first suspected of being an essential dietary trace element in the 1950s. We now know that indeed it is an essential biological element that serves as an integral component of several enzymes, including those in the families of deiodinases and glutathione peroxidases as well as selenoproteins P and W. The multi-author review that follows this introduction concentrates on the important biological role of selenium in enzymes as well as some of the physiological aspects of selenium as either a potential anticarcinogenic agent or insulin mimetic. What should become clear from these contributed articles is the complex and dynamic role that selenium plays in many biological processes and that the investigations in these areas are at the edge of exciting new frontiers. PMID- 11215509 TI - The glutathione peroxidases. AB - There are several proteins in mammalian cells that can metabolize hydrogen peroxide and lipid hydroperoxides. These proteins include four selenium containing glutathione peroxidases that are found in different cell fractions and tissues of the body. This review considers the structure and distribution of the selenoperoxidases and how this relates to their biological function. The functions of the selenoperoxidases were originally studied in systems where their activity was manipulated by changing dietary selenium levels. More recently, molecular techniques have allowed overexpression of selenoperoxidases in cell lines and animals. Additionally, cellular glutathione peroxidase knockout mice have been used to investigate the functions of this protein. From this work it is clear that the selenoperoxidases are involved in cell antioxidant systems. However, they also have more subtle functions in ensuring the regulation and formation of arachadonic acid metabolites that are derived from hydroperoxide intermediates. The range of biological processes, which are potentially dependent on optimal selenoperoxidase activity in mammals, emphasises the importance of achieving adequate selenium intake in the diet. PMID- 11215510 TI - Selenoprotein P. AB - Selenoprotein P (SeP) is an extracellular, monomeric glycoprotein containing up to 10 selenocysteine residues in the polypeptide chain. It is ubiquitously expressed in mammalian tissues, and in human plasma it accounts for at least 40% of the total selenium concentration. SeP binds to heparin and cell membranes, and is associated with endothelial cells. SeP in human plasma protects against peroxynitrite-mediated oxidation and reduces phospholipid hydroperoxide in vitro, in accordance with the presumption that it has a function as an extracellular oxidant defense. Immunochemical assays have demonstrated that its concentration in plasma varies much with selenium intake, but other factors also have an influence. PMID- 11215511 TI - Selenoprotein W: a review. AB - Purification of selenoprotein W (Se-W) from rat and monkey muscles was shown to exist in multiple forms: with or without reduced glutathione and/or a 41-Da moiety (identity still unknown). TGA is located at coding position 13 in Se-W complementary DNA (cDNA) from all five species studied (rats, mice, sheep, human and monkey). TGA is also the stop codon in the rodents and sheep cDNA, but TAA is the stop codon in primates. There is an 80% homology of the nucleotide sequence in the coding region among the five species of animals, and the predicted amino acid sequences are 83% identical (rodents identical and primates identical). Se-W levels are highest in muscle, heart and brain from sheep and primates, but very low in rodent hearts. Studies with tissue cultures of muscle and brain cells indicated that selenium influenced Se-W levels. Although the metabolic function of Se-W is unknown, preliminary data suggest that it has an antioxidant function. PMID- 11215512 TI - The deiodinase family: selenoenzymes regulating thyroid hormone availability and action. AB - Thyroid hormones control growth, development, differentiation and metabolism in vertebrates. Most of the actions of the active thyroid hormone T3 (3,5,3'-triiodo L-thyronine) are exerted via ligand-activated nuclear T3 receptors. Activation of the secretory product of the thyroid gland, L-thyroxine (3,3',5,5'-tetraiodo-L thyronine), or T4, is catalyzed by two enzymes, iodothyronine-5'-deiodinases type I and type II. Inactivation of T4 and T3 occurs via type III iodothyronine-5 deiodinase and to some extent by type I 5'deiodinase. Complementary DNAs (cDNAs) encoding the substrate-binding selenocysteine-containing subunits of the deiodinases were cloned, though some controversy still exists on the type II 5' deiodinase subunits. Characterization of tissue-specific expression patterns indicates that these selenium-dependent enzymes exert tight control on local and systemic availability of active T3. Thus, deiodinases are envisaged as guardians to the gate of thyroid hormone action mediated by T3 receptors. PMID- 11215513 TI - Anticarcinogenic effects of selenium. AB - Selenium (Se) exerts its anticarcinogenic effects by multiple mechanisms. In the physiological dosage range, Se appears to function as an antimutagenic agent, preventing the malignant transformation of normal cells and the activation of oncogenes. These protective effects of Se seem to be primarily associated with its presence in the glutathione peroxidases, which are known to protect DNA and other cellular components from damage by oxygen radicals. Selenoenzymes are also known to play roles in carcinogen metabolism, in the control of cell division, oxygen metabolism, detoxification processes, apoptosis induction and the functioning of the immune system. Other modes of action, either direct or indirect, may also be operative, such as the partial retransformation of tumor cells and the inactivation of oncogenes. However, the effects of Se in the physiological dosage range are not attributable to cytotoxicity, allowing Se to be defined as a genuine nutritional cancer-protecting agent. The anticarcinogenic effects of Se are counteracted by Se-antagonistic compounds and elements. For maximal utilization of its cancer-protective potential, Se supplementation should start early in life and be maintained over the entire lifespan. In addition, exposure to Se antagonists and carcinogenic risk factors should be minimized by appropriate dietary and lifestyle changes. PMID- 11215514 TI - Selenium: an insulin-mimetic. AB - Insulin or agents that can mimic its action (insulin-mimetics) are necessary to promote the entry of glucose into tissues where the glucose can either be converted into energy or stored for later use. In recent years, selenium has been shown to mediate a number of insulin-like actions both in vivo and in vitro. These insulin-like actions include stimulating glucose uptake and regulating metabolic processes such as glycolysis, gluconeogenesis, fatty acid synthesis and the pentose phosphate pathway. The mechanism by which selenium is capable of mimicking insulin is not clear; however, reports indicate that selenium does activate key proteins involved in the insulin-signal cascade. Various proteins in the insulin-signal cascade have been shown to be necessary for different insulin regulated events, and presumably data will be forthcoming soon that illustrate this similarly for selenium. This review compares the action of selenium to that of insulin and discusses the available evidence in support of selenium as an insulin-mimetic. PMID- 11215515 TI - Biosynthesis of cobalamin (vitamin B12): a bacterial conundrum. AB - The biosynthesis of cobalamin (vitamin B12) is described, revealing how the concerted action of around 30 enzyme-mediated steps results in the synthesis of one of Nature's most structurally complex 'small molecules'. The plethora of genome sequences has meant that bacteria capable of cobalamin synthesis can be easily identified and their biosynthetic genes compared. Whereas only a few years ago cobalamin synthesis was thought to occur by one of two routes, there are apparently a number of variations on these two pathways, where the major differences seem to be concerned with the process of ring contraction. A comparison of what is currently known about these pathways is presented. Finally, the process of cobalt chelation is discussed and the structure/function of the cobalt chelatase associated with the oxygen-independent pathway (CbiK) is described. PMID- 11215516 TI - Alpha-synuclein and Parkinson's disease. AB - The involvement of alpha-synuclein in neurodegenerative diseases was first suspected after the isolation of an alpha-synuclein fragment (NAC) from amyloid plaques in Alzheimer's disease (AD). Later, two different alpha-synuclein mutations were shown to be associated with autosomal-dominant Parkinson's disease (PD), but only in a small number of families. However, the discovery that alpha synuclein is a major component of Lewy bodies and Lewy neurites, the pathological hallmarks of PD, confirmed its role in PD pathogenesis. Pathological aggregation of the protein might be responsible for neurodegeneration. In addition, soluble oligomers of alpha-synuclein might be even more toxic than the insoluble fibrils found in Lewy bodies. Multiple factors have been shown to accelerate alpha synuclein aggregation in vitro. Therapeutic strategies aimed to prevent this aggregation are therefore envisaged. Although little has been learned about its normal function, alpha-synuclein appears to interact with a variety of proteins and membrane phospholipids, and may therefore participate in a number of signaling pathways. In particular, it may play a role in regulating cell differentiation, synaptic plasticity, cell survival, and dopaminergic neurotransmission. Thus, pathological mechanisms based on disrupted normal function are also possible. PMID- 11215517 TI - Ferrochelatase at the millennium: structures, mechanisms and [2Fe-2S] clusters. AB - Ferrochelatase (E.C. 4.99.1.1, protoheme ferrolyase) catalyzes the insertion of ferrous iron into protoporphyrin IX to form protoheme (heme). In the past 2 years, the crystal structures of ferrochelatases from the bacterium Bacillus subtilis and human have been determined. These structures along with years of biophysical and kinetic studies have led to a better understanding of the catalytic mechanism of ferrochelatase. At present, the complete DNA sequences of 45 ferrochelatases from procaryotes and eucaryotes are available. These sequences along with direct protein studies reveal that ferrochelatases, while related, vary significantly in amino acid sequence, molecular size, subunit composition, solubility, and the presence or absence of nitric-oxide-sensitive [2Fe-2S] cluster. PMID- 11215518 TI - Mitochondrial defects and hearing loss. AB - The techniques of human molecular genetics have been rapidly applied to the study of hearing loss. These studies have implicated more than 60 loci as causes of nonsyndromic hearing loss. Mutations at more than a dozen nuclear genes have been demonstrated to cause hearing loss, and these have been covered in recent reviews. However, a perhaps unexpected feature of the molecular characterization of human hearing loss has been the occurrence of mutations in the mitochondrial DNA (mtDNA). The importance of mitochondrial function in hearing is emphasized by the recent discovery of mutations in a nuclear-encoded mitochondrial protein which results in hearing loss. This article reviews the current status of our knowledge of mtDNA mutations that have been shown to cause hearing loss, and the suggestion of potential molecular, cellular and tissue-specific pathophysiological mechanisms by which dysfunction of mitochondria may lead to a loss of hearing. PMID- 11215519 TI - Regulation of the type III InsP3 receptor and its role in beta cell function. AB - The type III inositol 1,4,5-trisphosphate receptor (InsP3R) is an important intracellular calcium (Ca2+) release channel in the pancreatic beta cell. Pancreatic beta cells secrete insulin following a characteristic change in membrane potential that leads to an increase in cytoplasmic Ca2+. Both extracellular Ca2+ and Ca2+ mobilized from InsP3-sensitive stores contribute to this increase. RIN-m5F cells, an insulin-secreting beta cell line, preferentially express the type III InsP3R. These cells have been useful in determining the regulatory properties of the type III InsP3R and the role of this isoform in an intact cell. The type III InsP3R is ideal for signal initiation because high cytoplasmic Ca2+ does not inhibit its activity. Altered insulin secretion, the result of changes in Ca2+ handling by the beta cell, has significant clinical consequences. PMID- 11215521 TI - Polysialic acids: potential in improving the stability and pharmacokinetics of proteins and other therapeutics. AB - Naturally occurring polymers of N-acetylneuraminic acid (polysialic acids) are biodegradable, highly hydrophilic and have no known receptors in the body. Following intravenous injection, polysialic acids exhibit long half-lives in the blood circulation and have therefore been proposed as carriers of short-lived drugs and small peptides. In addition, shorter-chain polysialic acids can be used as a means to increase the circulatory half-life of proteins and thus serve as an alternative to the nonbiodegradable monomethoxypoly(ethylene glycol). Recent work has shown that covalent coupling of a low molecular weight polysialic acid (colominic acid) to catalase and asparaginase leads to a considerable increase of enzyme stability in the presence of proteolytic enzymes or blood plasma. Comparative studies in vivo with polysialylated and intact asparaginase revealed that polysialylation significantly increases the half-life of the enzyme. The highly hydrophilic and innocuous nature of polysialic acids renders them suitable as a means to prolong the circulation of peptides and proteins. PMID- 11215520 TI - The role of ras and other low molecular weight guanine nucleotide (GTP)-binding proteins during hematopoietic cell differentiation. AB - Recent progress in the understanding of signal transduction and gene regulation in hematopoietic cells has shown that many intracellular signalling pathways are modulated by low molecular weight guanine nucleotide (GTP)-binding proteins (LMWGs). LMWGs act as molecular switches for regulating a wide range of signal transduction pathways in virtually all cells. In hematopoietic cells, LMWGs have been shown to participate in essential functions such as growth control, differentiation, cytoskeletal organization, cytokine and chemoattractant-induced signalling events, reduced nicotinamide adenine dinucleotide phosphate oxidase activity, intracellular vesicle transport and secretion. In human leukemias, myelodysplastic syndromes and myeloproliferative disorders, Ras activation occurs by point mutations, overexpression or by alteration of NF-1 Ras-GTPase activating protein (GAP). These are postinitiation events in leukemia but may modulate growth-factor-dependent and independent leukemic growth. Two animal models of mutated N-ras expression resulting in myelodysplastic and myeloproliferative features are discussed. The role of Ras in organ development is discussed in the context of transgenic knockout mice. More LMWG functions will certainly be identified as we gain a better understanding of regulatory pathways modulating myeloid signal transduction. This review will summarize our current understanding of this rapidly advancing area of research. PMID- 11215522 TI - Protein surface similarities: a survey of methods to describe and compare protein surfaces. AB - Many methods have been developed to analyse protein sequences and structures, although less work has been undertaken describing and comparing protein surfaces. Evolution can lead sequences to diverge or structures to change topology; nevertheless, surface determinants that are essential to protein function itself may be mantained. Moreover, different molecules could converge to similar functions by gaining specific surface determinants. In such cases, sequence or structure comparisons are likely to be inadequate in describing or identifying protein functions and evolutionary relationships among proteins. Surface analysis can identify function determinants that are independent of sequence or secondary structure and can therefore be a powerful tool to highlight cases of possible convergent or divergent evolution. This kind of approach can be useful for a better understanding of protein molecular and biochemical mechanisms of catalysis or interaction with a ligand, which are usually surface dependent. Protein surface comparison, when compared to sequence or structure comparison methods, is a hard computational challenge and evaluated methods allowing the comparison of protein surfaces are difficult to find. In this review, we will survey the current knowledge about protein surface similarity and the techniques to detect it. PMID- 11215523 TI - Lysophosphatidic acid: receptors, signaling and survival. AB - Though the mitogenic activity of lysophosphatidic acid (LPA) has been well established through classical studies, its mechanism of action was long obscure. Recent identification and cloning of LPA-specific receptors has led to the elucidation of the G-proteins and signaling pathways through which this molecule functions. In addition to its mitogenic properties, recent reports have suggested that LPA may also promote cell survival. This review will summarize the current literature regarding LPA signaling and its role as an antiapoptotic factor. PMID- 11215524 TI - Effect of plant lectins on Ustilago maydis in vitro. AB - Ustilago maydis is an edible parasitic basidiomycete, which specifically infects corn (Zea mays) and teocintle (Z. diploperennis). To characterise the interaction between the basidiomycete and its host organism, we tested the effect of plant lectins with well-known sugar specificity on the growth and germination of U. maydis spores. Lectins specific for N-acetyl-D-galactosamine, such as those from Dolichos biflorus and Phaseolus lunatus, and the wheatgerm agglutinin specific for N-acetyl-D-glucosamine inhibited spore germination, but were ineffective in modifying U. maydis cell growth. The galactose-specific lectin from the corn coleoptyle inhibited both germination and cell growth, while the lectin concanavalin A (mannose/glucose specific) activated spore germination and growth. Our results suggest that specific saccharide-containing receptors participate in regulating the growth and maturation of U. maydis spores. PMID- 11215525 TI - A morphological study of the expression of the small G protein RhoA in resting and activated MDCK cells. AB - The small G protein Rho subfamily controls several cellular events such as growth, movement, proliferation and differentiation by rearranging actin and cytoskeleton proteins. Most of these effects are mediated by the activation of growth factor and extracellular matrix molecule receptors, suggesting a role for Rho molecules in the transduction pathway of these receptors. Despite the importance of Rho peptides in fundamental cellular events, data on their subcellular immunolocalisation are sparse: here we investigated the expression and subcellular localisation of RhoA in resting (cultured on plastic) and activated (Matri-cell or hepatocyte growth factor) MDCK cells by immunoperoxidase and immunogold techniques. Resting MDCK cells contain detectable amounts of RhoA mainly localised in the cytoplasm; RhoA expression is significantly enhanced by Matri-cell substrates that promote translocation of RhoA at the membrane level. This enhancing effect is reduced after exposure to hepatocyte growth factor. PMID- 11215527 TI - Perfusion-contraction match and mismatch. AB - The present article describes the concept of perfusion-contraction matching originally proposed by Ross, goes on to critically discuss the available techniques to measure both regional myocardial blood flow and function in the experimental and clinical setting, and finally analyzes the available evidence for perfusion-contraction match and mismatch during normoperfusion and various scenarios of myocardial ischemia/reperfusion, including acute and subacute ischemia, coronary microembolization, stunning and hibernation. PMID- 11215526 TI - Tyrosine phosphorylation of cytoplasmic proteins in proliferating, differentiating, apoptotic HL-60 cells and blood neutrophils. AB - Two-dimensional electrophoretic analysis was used to assess quantitative and qualitative changes in the expression and tyrosine phosphorylation of cytoplasmic proteins of proliferating, differentiating HL-60 cells and mature human blood neutrophils. The total tyrosine phosphorylation level of cytoplasmic proteins appeared approximately constant during the pre-commitment period, i.e., 6-24 h after induction of differentiation by 700 nM all-trans retinoic acid. At the time of granulocytic phenotype formation (48-120 h), the total level of tyrosine phosphorylation of cytoplasmic proteins increased significantly. Tyrosine phosphorylation of cytoplasmic proteins in matured blood neutrophils was significantly lower than that of cytoplasmic proteins of HL-60 cells differentiated for 96 h with retinoic acid. Immunoblotting with anti-Erk2 and anti-phosphotyrosine monoclonal IgG2bk antibodies showed that Erk2 was expressed and tyrosine-phosphorylated at different levels in HL-60 proliferating cells and in cells at all stages of differentiation. Our data showed that tyrosine phosphorylation of cytoplasmic proteins in differentiating HL-60 cells changes dramatically during the period of phenotype formation and is accompanied by increasing activity of Erk2. An increasing number of apoptotic cells appeared in the differentiating HL-60 cell population during the granulocyte maturation stage (48-120 h of differentiation). The appearance at this time of differentiation of a new set of tyrosine-phosphorylated cytoplasmic proteins (also distinctive for apoptotic HL-60 cells mediated by etoposide) together with an increasing number of apoptotic cells in the differentiating population strongly suggests that these proteins are associated with the apoptotic process. PMID- 11215528 TI - Apoptosis in the vascular wall and atherosclerosis. AB - Apoptosis, programmed cell death, has emerged as a key element in the complex pathophysiology underlying the development as well as the progression of atherosclerosis. A number of recent reports provided evidence for both in vivo and in vitro occurrence of apoptotic cell death of vascular cells, namely endothelial cells, macrophages, and vascular smooth muscle cells. In addition, functional studies in disease models underscore the relevance of these findings for the understanding of processes which lead to lesion development, plaque rupture, and thrombus formation. Pathomechanistic in vitro investigations provided an increasingly detailed picture of the involved intracellular signaling pathways that regulate onset and execution of apoptosis. These insights offer the potential of therapeutic interventions targeted to interfere with the molecular processes involving apoptotic cell death in the vascular wall. PMID- 11215529 TI - Cardiac isoform of alpha-2 macroglobin, a novel serum protein, may induce cardiac hypertrophy in rats. AB - Earlier studies from this laboratory have identified a novel high molecular weight (182 kDa) serum protein suggested to be involved in the development of cardiac hypertrophy. In the present case the role of this novel serum protein in the development of pressure-induced cardiac hypertrophy and the molecular events associated with it in experimental rats has been investigated. Multiple injections of this purified protein intravenously (through tail vein) into the normal animals lead to the development of cardiac hypertrophy and this is accompanied by an induction of muscle specific genes such as that of MLC2 and beta-MHC characteristic of pressure overloaded heart. Further, the hypertrophy specific serum protein has been found to be identical to rat alpha-2 macroglobulin (alpha-2M) in molecular weight (182 kDa) and in its appearance in blood serum. alpha-2M is an acute phase serum protein that increases markedly after inflammatory stimuli in hepatocytes in liver and gets secreted into the blood. The studies at present suggest that the 182kDa serum protein that appeared during the early stage of development of cardiac hypertrophy in aorta constricted rats is a glycoprotein localized in the heart that showed immunological cross reactivity with alpha-2M and is expressed in the heart as evinced by Northern blot analysis. Further this protein showed certain differences from rat alpha-2M under denaturing conditions in isoelectric focusing and partial peptide mapping. Partial peptide sequencing of the internal peptides of tryptic digest of 182 kDa showed 100% identity of the sequences with alpha-2M sequences. Rat alpha-2M does not, however, have any influence on the development of cardiac hypertrophy and its antibody does not cross react with the 182 kDa protein. These data suggest that the 182 kDa protein that may play an indispensable role in the development of cardiac hypertrophy in experimental rats is cardiac specific, and may be an isoform of liver alpha-2M belonging to macroglobulin family. PMID- 11215530 TI - Interaction between the opposing functional effects of cyclic AMP and cyclic GMP in hypertrophic cardiac myocytes. AB - We tested the hypothesis that in isolated cardiac myocytes, the negative functional effects of cyclic GMP would be blunted when the level of cyclic AMP was increased and that this interaction would be altered in renal hypertensive (One-Kidney-One-Clip, 1K1C) cardiac hypertrophic rabbits. Using isolated control and 1K1C ventricular myocytes, cyclic AMP and cell shortening (%) data were collected: 1) at baseline, 2) after the addition of 8-Br-cGMP 10(-7), -6, -5 M, and 3) after forskolin (10(-6) M), an adenylate cyclase activator, followed by 8 Br-cGMP 10(-7), -6, -5 M. Basal levels of cyclic AMP were similar in control vs. 1K1C myocytes (10.2 +/- 1.6 vs. 11.3 +/- 2.6 pmol/10(5) myocytes). We found that 8-Br-cGMP decreased the percent shortening in a dose related manner in both control myocytes (5.1 +/- 0.6 to 3.2 +/- 0.4%) and hypertrophic myocytes (5.2 +/- 0.4 to 3.6 +/- 0.5). The level of cyclic AMP significantly increased after the addition of 8-Br-cGMP in control myocytes (14.1 +/- 2.1), but not in 1K1C myocytes. Forskolin increased the percent shortening in the control myocytes (3.8 +/- 0.1 to 4.8 +/- 0.4), but no significant increase was noted in the hypertrophic myocytes (3.6 +/- 0.3 to 3.7 +/- 0.3). The level of cyclic AMP significantly increased after the addition of forskolin in both control (13.9 +/- 2.0), and 1K1C cells (14.6 +/- 3.8). Forskolin attenuated the negative functional effects of 8-Br-cGMP in the control (4.8 +/- 0.4 to 3.2 +/- 0.1) and 1K1C myocytes (3.7 +/- 0.3 to 2.7 +/- 0.3). The addition of 8-Br-cGMP did not affect the level of cyclic AMP after forskolin in either control (13.9 +/- 2.0 to 14.8 +/- 2.5) or 1K1C myocytes (14.6 +/- 3.8 to 13.8 +/- 1.9). These data indicated that in hypertrophic cardiac myocytes the negative functional effects of 8-Br cGMP were similar to control, but the positive functional effects of cyclic AMP were blunted. There was an increase in cyclic AMP levels after addition of 8-Br cGMP in control but not 1K1C cells. We conclude that in control and hypertrophic myocytes, the effects of cyclic GMP were blunted after forskolin, but this did not seem to be related to cyclic AMP phosphodiesterase activity. PMID- 11215531 TI - Integrins alphavbeta3 and alphavbeta5 mediate VSMC migration and are elevated during neointima formation in the rat aorta. AB - Neointima formation involves tissue expression of matrix proteins and growth factors. The role of alphavbeta3, but not alphavbeta5 integrin in vascular cells has been sufficiently investigated. The aim of the present study was to determine and compare the function of alphavbeta3 and alphavbeta5 integrins in rat aortic (RASMC) and human coronary vascular smooth muscle cells (HCSMC) and to characterize their expression accompanying neointima formation in vivo. RASMC and HCSMC express alphavbeta3 and alphavbeta5 integrin subunits. The alphavbeta5 integrin predominantly mediated adhesion of RASMCs to vitronectin and spreading on vitronectin via RGD-binding sequences. In contrast, the alphavbeta3 integrin did not contribute to the adhesion and spreading on fibronectin, vitronectin, gelatin or collagen I coated layers. PDGF-directed migration through gelatin coated membranes involved both alphavbeta3 and alphavbeta5 integrins. Selective blocking antibodies for alphavbeta3 and alphavbeta5 inhibited migration of RASMC and HCSMC by more than 60 % (p < 0.01). Integrin expression was studied in vivo in thoracic aorta of Sprague Dawley rats before and after balloon injury. In situ hybridization demonstrated low signals for alphav, beta3 and beta5 mRNA in uninjured aorta, which increased significantly at 14 days, localized predominantly in the neointima. Northern analysis of aorta after 14 days of injury also demonstrated an upregulation of alphav, beta3 and beta5 mRNA compared to uninjured aorta. Consistent with the increase in message levels, increased integrin protein expression was seen in the neointima after 7 and 14 days. This study provides evidence that alphavbeta3 and alphavbeta5 are elevated during neointima formation in the rat and indicates a novel role for alphavbeta5 participating in mechanisms regulating smooth muscle cell migration. PMID- 11215532 TI - Phosphorylation of cytokeratin 8 and 18 in human vascular smooth muscle cells of atherosclerotic lesions and umbilical cord vessels. AB - Expression of cytokeratins (CK) is considered a hallmark of the state of epithelial differentiation. CK also occur in certain vascular smooth muscle cells (VSMC), inferring an association with a less differentiated phenotype. Recently, CK posttranslational modification was shown to occur in epithelial cells in stress, mitosis or apoptosis. The aim of this study was to determine potential CK phosphorylation patterns in human VSMC. Tissue samples of normal peripheral and coronary arteries, atherosclerotic lesions and umbilical cord vessels were evaluated by immunofluorescence microscopy applying antibodies specific for cytokeratins 8 and 18, specific cytokeratin phosphorylation sites, Ki-67-antigen as a proliferation marker and nick end labeling (TUNEL) to detect apoptosis. All samples contained cytokeratin-positive VSMC but diverse phosphorylation patterns. The C-terminal serine 431 of cytokeratin 8 (CK8Ser-431) was phosphorylated in the vast majority of CK-expressing VSMC of coronary artery lesions. Only a subset of these cells demonstrated phosphorylation of CK18Ser-33 or, to an even lesser extent, CK8Ser-73. DNA fragmentation occurred predominantly in samples containing cells with phosphorylated CK8Ser-431 domains. In contrast, occluded peripheral lesions exhibited little or no phosphorylation. Neonatal VSMC in umbilical cord vessels contain abundant phosphorylated CK domains, again predominantly CK8Ser 431, but also CK18Ser-33. Again, only single cells were found to be proliferating or to contain DNA fragmentation. Thus, abundant CK phosphorylation in VSMC of atherosclerotic lesions suggests a specific functional response to cell stress and a possible relation to apoptosis. PMID- 11215533 TI - Serotonin-induced human coronary microvascular contraction during acute myocardial ischemia is blocked by COX-2 inhibition. AB - Since serotonin (5-HT) is implicated in exacerbating acute coronary syndromes, we studied the reactivity of atrial coronary arterioles (70-140 microm) of atherosclerotic patients undergoing cardiac surgery to 5-HT, substance P (Sub P), and sodium nitroprusside by video-microscopy. Before ischemia, 5-HT-induced relaxation was not affected by NS398 (cyclooxygenase inhibitor), H2O2 or U63557A (thromboxane A2 synthase inhibitor), but was reduced by L-NNA. 5-HT elicited a potent contractile response after ischemia that was inhibited by NS398, Indo, and U63557A. While Sub P relaxation was decreased after ischemia, SNP relaxation was unchanged. The mRNA steady-state levels of NOS-3, NOS-2, prostacyclin synthase, and COX- 1 were not altered by ischemia. COX-2 mRNA and protein levels (Westernblotting), however, were increased (mean +/- SEM) 2.4 +/- 0.4 and 3.2 +/- 0.7 fold, respectively, in ischemic atrium corroborating with the immunohistochemistry of atrial tissue. It is concluded that myocardial ischemia enhanced contractile response of coronary arterioles to 5-HT maybe due to the stimulated prostaglandin release (likely thromboxane A2) secondary to induction of COX-2 expression. These findings may have implications regarding the cause of coronary spasm during acute myocardial ischemia. PMID- 11215534 TI - Ischemia-induced ventricular fibrillation in isolated perfused rat heart: role of alpha1A-adrenoceptor mediated activation of protein kinase C. AB - It previously has been reported in ischemic rat hearts that local release of noradrenaline triggers ventricular fibrillation via alpha1A-adrenoceptor stimulation. In order to elucidate the intracellular pathway mediating ventricular fibrillation in this setting, we used inhibitors or activators of protein kinase C in the absence or presence of the alpha1A-adrenoceptor antagonist WB 4101. Regional ischemia was induced in isolated perfused rat heart byligature of the left coronary artery. Pharmacological interventions were tested by addition of drugs to the perfusate 10 min prior to ligature and throughout 30 min of ischemia while the epicardial electrocardiogram was continuously monitored. Blockade of protein kinase C by polymyxin B (1 micromol/l) significantly reduced ventricular fibrillation to 40% (from 87% in controls). Similar effects were seen with the protein kinase C inhibitors staurosporine 10 nmol/l (46% vs. 91%) and cremophor RH 40 100 micromol/l (33% vs. 77%). Activation of protein kinase C by 1,2-dioctanoyl-sn-glycerol (DOG, 10 micromol/l) or phorbol 12-myristate 13-acetate (PMA, 10 nmol/l) did not affect ventricular fibrillation. In the presence of the alpha1A-adrenoceptor antagonist WB 4101 (0.1 micromol/l), which per se suppressed ventricular fibrillation to 17%, both DOG and PMA increased the occurrence of ventricular fibrillation to 73% and 75%, respectively, whereas the inactive phorbol ester 4alpha-phorbol 12,13-didecanoate (4alpha-PDD, 10 nmol/l) revealed no proarrhythmic effect. In summary, during regional ischemia in the isolated perfused rat heart, alpha1A-adrenoceptor stimulation induces ventricular fibrillation mainly by activating protein kinase C. PMID- 11215535 TI - Antiendothelial antibodies in sera of patients with infective endocarditis. AB - Infective endocarditis is characterized by the colonization of endocardium by microorganisms. Except for Staphylococcus aureus, microorganisms are not able to adhere to and grow on endocardial cells; prior damage, e.g., by shear stress or other mechanical factors, is necessary. But other causes may well have a share. This study was, therefore, designed to identify immunological factors, especially antibodies against endothelial cells, which could contribute to the initiation of endocardial injury. Sera of patients with infective endocarditis and healthy controls were investigated for the presence of antibodies against endothelial antigen. As the antigen source human umbilical vein endothelial cells were used. Antibodies against endothelial cells were detected by indirect immunofluorescence, ELISA, immunoblotting, antibody dependent cellular cytotoxicity, and antibody mediated cytotoxicity. Antibodies against endothelial cells were found in seven out of fifteen patients. These antibodies were directed against cytoplasmic structures and only appeared in the course of the disease. A correlation between the presence of these antibodies and disease activity or the outcome of disease was not observed. These antibodies may develop as a consequence of damage to endocardial cells (thereby exposing intracellular antigen to the immune system) and do not seem to play a role in the pathogenesis of infective endocarditis. PMID- 11215536 TI - Atrial L-type Ca2+-channel, beta-adrenorecptor, and 5-hydroxytryptamine type 4 receptor mRNAs in human atrial fibrillation. AB - Molecular and electrical remodeling of ion channels determining action potential duration has been proposed as a major mechanism in chronic atrial fibrillation. We investigated the mRNA expression of the cardiac L-type Ca2+-channel subunits alpha1c, alpha2/delta1, beta1a, and beta1b/c in atrial tissue of patients with chronic atrial fibrillation compared to patients in sinus rhythm. In addition, the mRNA expression of the 5-hydroxytryptamine type 4-, beta1-, and beta2 adrenergic receptors, which are known to stimulate the L-type Ca2+-current in human atrium, was analyzed and the effect of chronic beta-blocker treatment on the mRNA expression of these receptors and of the L-type Ca2+-channel subunits was assessed. Total RNA was isolated from right atrial appendages of patients in sinus rhythm and of patients with chronic atrial fibrillation. Then, semiquantitative RT-PCR using 18S RNA as the "housekeeping gene" was performed. In patients with chronic atrial fibrillation, there were only mild reductions in mRNA expression of the alpha1c-subunit (-15.5 %, p = 0.13), and of the beta1 subunit isoforms a and c (-13.3 %, p = 0.14 and -16.6%, p = 0.18, respectively). However, mRNA expression of the alpha2/delta1-subunit (-31.5 %, p < 0.01) and of the beta1-subunit isoform b (-39.9 %, p < 0.0005) was significantly reduced in patients with chronic AF. Taken together, the mRNA expression of the beta1 subunit isoforms b and c, which are splice variants, was significantly down regulated by 26.5 % (p < 0.05) in these patients. The analysis of the beta1c/beta1b ratio resulted in a significant shift by 39.2 % (p < 0.0001) in favor of beta1c in patients with chronic atrial fibrillation. In the AF patients, the abundance of the 5-HT4-receptor transcript was significantly reduced by 36 % (p < 0.05). The beta-adrenoreceptor transcription was unchanged. In both SR and AF patients, chronic beta-blocker treatment did neither significantly effect the mRNA expression of the L-type Ca2+-channel subunits, the beta-adrenoreceptor subtypes 1 and 2, nor that of the 5-HT4-receptor. Our data show that chronic AF is associated with a decrease in the atrial mRNA amount of auxiliary subunits of the L-type Ca2+-channel and of the 5-HT4-receptor. This supports the hypothesis that the observed alterations in mRNA transcription in AF patients may lead to a decrease in the availability of functional L-type Ca2+-channels and 5-HT4 receptors and/or reduce L-type Ca2+-current amplitude and density, thus, promoting and stabilizing the arrhythmia. PMID- 11215537 TI - Pulmonary beta adrenoceptor density in arrhythmogenic right ventricular cardiomyopathy and idiopathic tachycardia. AB - OBJECTIVE: In recent in vivo studies using positron emission tomography (PET) our group demonstrated that the myocardial beta adrenoceptor (betaAR) density is reduced in arrhythmogenic right ventricular cardiomyopathy (ARVC) and idiopathic right ventricular outflow tract tachycardia (RVO-VT) associated with an increased presynaptic catecholamine washout. It was hypothesised that the reduction of myocardial betaAR density is secondary to an increase of local catecholamines in the myocardium resulting from the presynaptic dysfunction since circulating plasma catecholamines were demonstrated to be unchanged in these conditions. To further prove this hypothesis of an organ-limited adrenergic nervous dysfunction of the heart, this study aimed to investigate betaAR density in another thoracic organ, the lung. METHODS: Pulmonary and myocardial betaAR density was measured in 7 ARVC patients, 8 RVO-VT patients and in a group of healthy controls (n = 13) using the non-selective beta-blocker [11C]-CGP 12177 and PET. RESULTS: Pulmonary betaAR density was similar in controls (12.4 +/- 1.7 pmol/g tissue), ARVC (11.6 +/- 1.7 pmol/g tissue, p = ns) and RVO-VT (12.8 +/- 2.0 pmol/g tissue, p = ns), whereas myocardial betaAR density was significantly reduced in ARVC (6.3 +/- 1.1 pmol/g tissue, p = 0.006) and RVO-VT (6.8 +/- 1.2 pmol/g tissue, p=0.02) as compared to controls (8.8+/-1.5 pmol/g tissue). CONCLUSION: The unchanged pulmonary betaAR density in the presence of a previously described significant reduction in myocardial betaAR density in the same patient principally supports our pathophysiological hypothesis that the myocardial betaAR density may be reduced in ARVC and RVO-VT because of an increase in local synaptic catecholamine levels due to an organ-limited presynaptic adrenergic dysfunction of the heart. Since in the present study only pulmonary betaAR density was measured, future functional studies excluding pulmonary betaAR desensitisation are required to finally prove the unchanged pulmonary sympathetic innervation in ARVC and RVO-VT. PMID- 11215538 TI - Signal characteristics of multichannel epicardial electrograms in chronic ischaemic and scarred myocardium: electromechanical mismatch indicates viability in regions of myocardial dysfunction. AB - BACKGROUND: To predict the outcome after myocardial revascularisation, a clear separation between hibernation and/or repetitive stunning on the one hand and myocardial scarring on the other hand is of importance. METHODS AND RESULTS: A total of 44 patients was included in this study. In 35 patients with chronic myocardial ischaemia and an indication for coronary bypass-surgery, epicardial mapping of local activation was performed. Nine patients with LV aneurysm and an indication for antitachycardia surgery were also included. For simultaneous recording of the local electrograms during sinus rhythm, a sock electrode with 102 bipolar leads was used. The regional myocardial contraction pattern was assessed from preoperative angiograms and regional myocardial metabolism (viability) from 18F-FDG PET, respectively. The results were projected on the grid of the intraoperative position of the sock electrode. This enabled regional comparison of electrogram characteristics to local contraction patterns and viability. For the characterisation of local electrograms, peak-to-peak amplitude and duration of activation were calculated using custom-made automated computer algorithms. Dysfunctional but viable areas showed normal or almost normal electrographic signal characteristics. In contrast, dysfunctional and non-viable myocardium showed a distinct reduction of local amplitudes and prolongation of signal duration. These changes were even more intense in areas of LV aneurysms. CONCLUSIONS: In patients with chronic ischaemic myocardium, a mismatch between mechanical function and local electrogram characteristics was observed in areas with preserved metabolism. Thus, normal epicardial electrograms in regions of myocardial dysfunction may be an indicator for myocardial viability. PMID- 11215539 TI - "Schizotaxia": clinical implications and new directions for research. AB - We sought to show that (1) schizotaxia (Meehl's term for the predisposition to schizophrenia) is a clinically consequential condition, and (2) distinguishing it from schizotypal personality disorder may be useful from both clinical and scientific perspectives. We review the features of schizotaxia that may be relevant in clinical settings and discuss their implications for the diagnosis, psychosocial functioning, family intervention and treatment of people in schizophrenia families. Our review indicates that prior work finds some of the nonpsychotic and nonschizotypal relatives of schizophrenia patients to have a psychiatric syndrome characterized by negative symptoms, neuropsychological impairment, and psychosocial dysfunction. Following Meehl, we call this constellation of clinical and neurobiological features schizotaxia. The studies we review suggest it may be worthwhile to consider schizotaxia as a separate diagnostic class. Doing so would alert clinicians to a neurobehavioral syndrome not adequately covered by current diagnostic criteria and would motivate researchers to develop diagnostic and therapeutic approaches aimed at helping schizotaxic individuals and, perhaps, preventing the onset of schizophrenia. PMID- 11215540 TI - Gender differences in poor outcome patients with lifelong schizophrenia. AB - Gender effects have been reported quite consistently in schizophrenia, with male patients having an earlier age of onset, poorer functional outcome, greater negative symptoms and cognitive impairment, and less severe positive symptoms. Because age of onset, cognitive impairments, and negative symptoms are all correlated with poorer functional status, it is not clear if previously reported gender differences in symptoms are just recapturing gender differences in functional outcome. In this study, 205 geriatric patients with lifelong poor outcome schizophrenia (43% male) were examined for the severity of schizophrenic symptoms, cognitive impairments, and specific deficits in adaptive skills, as well as for demographic differences such as age at first psychiatric admission, premorbid education, and current treatment status. Previously reported gender differences were replicated in these patients with a uniformly poor functional outcome, with male patients having more severe negative symptoms and an earlier age of first psychiatric admission. No differences in cognitive functioning or specific functional deficits were found, however. These findings suggest that negative symptom severity is greater in male patients regardless of functional outcome and that the association of cognitive deficits with gender may be found only in patients with better functional outcome. The study of gender-related differences in brain structure or function and their interaction with overall course of illness might help understand these differences in symptom presentation. PMID- 11215541 TI - Subtyping schizophrenia according to outcome or severity: a search for homogeneous subgroups. AB - There is a growing consensus that current definitions of schizophrenia (SZ) include different disorders, or else different dimensions underlain by different pathophysiologies. This article reviews the evidence for the validity of three novel strategies to subtype SZ according to outcome or severity (deficit vs. nondeficit, Kraepelinian vs. non-Kraepelinian, congenital vs. adult-onset). Medline and bibliographies were used to locate articles. The methodology of the studies was reviewed, and their results were grouped according to seven validating criteria. Several differences were found between subtypes, particularly for the deficit/nondeficit subtypes. However, for most of these differences, replications have yet to be undertaken. Important indicators of etiology from the environmental risk factors and genetic domains have received very little attention. These three subtyping strategies represent promising attempts to address the etiologic heterogeneity of SZ. However, one cannot conclude whether these strategies identify etiologically distinct SZ subgroups. We propose ten methodological and conceptual recommendations for future studies aimed at the identification of valid SZ subtypes according to outcome or severity. PMID- 11215542 TI - Work-related social skills training for people with schizophrenia in Hong Kong. AB - This article describes a prospective blinded outcome study of a vocational social skills training program developed in Hong Kong for people affected by chronic schizophrenia. The aim was to improve their ability to find and keep a job. Participants were randomly assigned to three groups: a social skills training group with followup support, a social skills training group without followup support, and a comparison group who received standard after-care treatment. Participants who had participated in either of the training groups statistically outperformed those in the comparison group. Those receiving the training plus followup were statistically much more successful at finding and keeping a job than participants in either of the other two groups. A comparatively small amount of followup contact (a monthly group meeting or phone call) for 3 months after the training finished had a very significant effect on participants' success rate. PMID- 11215543 TI - Negative symptoms of schizophrenia and compliance with medication. AB - Poor compliance with medication has been reported in up to 40 percent of outpatients with schizophrenia. This study examines the relationship between compliance with depot neuroleptic medication and severity of negative symptoms of schizophrenia. Compliance with depot neuroleptic medication during the preceding year was calculated for 64 patients with a DSM-III-R diagnosis of schizophrenia. The severity of negative symptoms was assessed using the Scale for the Assessment of Negative Symptoms (SANS). Patients who complied poorly with medication had significantly greater severity of negative symptoms of schizophrenia, especially avolition, apathy, and alogia. Duration of illness and duration of prescribed medication were independently associated with compliance, but no other features were associated in the multiple regression model. These findings suggest that negative symptoms are one of the factors of importance in determining whether a patient will attend for depot neuroleptic medication. PMID- 11215544 TI - Working memory in schizophrenia: transient "online" storage versus executive functioning. AB - Working memory has been described as the temporary "online" storage and the subsequent manipulation and retrieval of information. It has been suggested that the prefrontal cortex is a primary site of working memory. Schizophrenia patients, who are thought to have prefrontal cortical dysfunction, have demonstrated inconsistent deficits on a variety of verbal and spatial working memory tests. This has led to questions about how to define and measure working memory, whether these deficits are distinct to one cognitive domain, and what role factors such as intelligence and symptoms play in working memory performance. We compared schizophrenia patients to normal comparison subjects in four separate studies. Based upon the results we recommend that working memory tests be characterized as either transient "online" storage and retrieval tasks (where short-term storage and retrieval of information is required) or executive functioning working memory tasks (where storage, manipulation, and retrieval of information is required). The importance of clearly identifying which distinct aspects of working memory are assessed is discussed. PMID- 11215545 TI - First person account: schizophrenia, medication, and outpatient commitment. AB - The article that follows is part of the Schizophrenia Bulletin's ongoing First Person Account series. We hope that mental health professionals-the Bulletin's primary audience--will take this opportunity to learn about the issues and difficulties confronted by consumers of mental health care. In addition, we hope that these accounts will give patients and families a better sense of not being alone in confronting the problems that can be anticipated by persons with serious emotional difficulties. We welcome other contributions from patients, ex patients, or family members. Our major editorial requirement is that such contributions be clearly written and organized, and that a novel or unique aspect of schizophrenia be described, with special emphasis on points that will be important for professionals. Clinicians who see articulate patients with experiences they believe should be shared might encourage these patients to submit their articles to Schizophrenia Bulletin, First Person Accounts, EEI Communications, 66 Canal Center Plaza, Suite 200, Alexandria, VA 22314.-The Editors. PMID- 11215546 TI - Depressive factors and their relationships with other symptom domains in schizophrenia, schizoaffective disorder, and psychotic depression. AB - Relationships among different symptom domains were investigated in patients with acute exacerbation of schizophrenia with depressive symptoms, psychotic depression, or schizoaffective disorder, depressive subtype. Scores for depression and depressive factors were correlated with positive, negative, and extrapyramidal symptoms within diagnostic categories. No between-group differences in the relationship of different symptom domains could be found, and no substantial relationship between depression and positive symptoms could be revealed in any diagnostic subgroup. Only the retardation factor of depression showed a significant overlap with negative symptoms; depressive core symptoms did not. Core symptoms of depression were independent from other symptoms in all investigated diagnostic groups. Depression seems to represent a heterogeneous symptom domain with unique relationships of components to positive and negative symptoms across nosological borders. A more differentiated assessment, analysis, and treatment of depressive symptoms is therefore recommended for patients with combined depressive and psychotic symptoms. PMID- 11215547 TI - Differences in rates of depression in schizophrenia by race. AB - The purpose of this study was to determine whether demographic and clinical factors are associated with a diagnosis of depression among persons with schizophrenia and to determine the association of depression with subjective quality of life. A consecutively admitted sample of psychiatric inpatients diagnosed with schizophrenia (n = 123) were assessed for depression and quality of life. Logistic regression was used to determine factors associated with a diagnosis of depression. Multiple regression analyses were used to determine the relationship between depression and quality of life. The odds of being diagnosed with depression were seven times greater in Caucasians than in African-Americans, and three times greater in persons who were ever married. Depression was significantly associated with reduced life satisfaction in Caucasians but not African-Americans. This suggests the importance of race as a predictor of a diagnosis of depression in schizophrenia and the possibility of underdiagnosis of depression among African-Americans. The absence of the expected association between depression and quality of life in African-Americans casts doubt on the validity of the depression diagnosis using conventional diagnostic tools. PMID- 11215548 TI - Confirmation of a two-factor model of premorbid adjustment in males with schizophrenia. AB - Because schizophrenia is considered to be a neurodevelopmental disorder, premorbid adjustment is of particular interest. Premorbid adjustment is probably not a unitary construct but rather is expressed across a number of developmental domains. The current investigation examined the validity of a two-factor model that differentiated premorbid adjustment across social and academic domains and evaluated relationships between these premorbid adjustment domains and other variables of interest. Participants with schizophrenia (n = 141) underwent evaluation of premorbid adjustment (using the Premorbid Adjustment Scale), intellectual functioning, and psychiatric symptoms. Using confirmatory factor analysis, a two-factor model of premorbid adjustment was identified that included an academic domain and a social domain. The social domain was associated with symptom variables, while the academic domain was associated with measures of intelligence. Results provide evidence for at least two domains of premorbid adjustment in schizophrenia. Distinguishing between these two premorbid domains may be theoretically important because of potential differences in incidence rates and deterioration courses; some individuals with schizophrenia may exhibit adequate academic adjustment but poor social adjustment, while others may exhibit the opposite pattern. PMID- 11215549 TI - Genetic and environmental influences on schizotypy: a community-based twin study. AB - This study investigated the factor structure and etiology of four self-report schizotypy questionnaires during young adulthood (age 18-27) in 98 monozygotic and 59 same-sex dizygotic twin pairs from the community. A single phenotypic factor was identified that was primarily associated with Perceptual Aberration, Magical Ideation, and the Rust Inventory of Schizotypal Cognitions scales, and less so with Social Anhedonia. Univariate etiologic models suggested that in addition to nonshared environmental influences, Perceptual Aberration and Social Anhedonia were significantly influenced by either genes or shared family environment, whereas Magical Ideation and the Rust Inventory were influenced by shared family environment, but not genes. Multivariate twin analyses detected a common schizotypy factor, primarily defined by Perceptual Aberration, Magical Ideation, and the Rust Inventory scales, that was influenced by genes or shared environment as well as nonshared environment. Contrary to expectations, these results suggest that, at least in community-based samples, these "positive" schizotypy questionnaires are not strongly genetically influenced. PMID- 11215550 TI - Latent class analysis of DSM-IV schizotypal personality disorder criteria in psychiatric patients. AB - The aim of the study was to evaluate the latent structure of DSM-IV schizotypal personality disorder (SPD) diagnostic criteria. The sample consisted of 564 consecutively admitted inpatients and outpatients. Exploratory latent class analysis identified a four-class model as the best fitting model for DSM-IV SPD criteria. The first of the SPD latent classes was mainly characterized by odd thinking, inappropriate affect, and interpersonal features; the second class by cognitive/perceptual difficulties; the third class by paranoid features; and the fourth class by absence of SPD features. The conditional probability pattern of the fourclass solution could be safely replicated across confounder strata. Unlike previous findings, oddness, aloofness, and social withdrawal, rather than positive symptoms, best characterized SPD even in clinical samples. PMID- 11215551 TI - The effect of family interventions on relapse and rehospitalization in schizophrenia--a meta-analysis. AB - Twenty-five intervention studies were meta-analytically examined regarding the effect of including relatives in schizophrenia treatment. The studies investigated family intervention programs to educate relatives and help them cope better with the patient's illness. The patient's relapse rate, measured by either a significant worsening of symptoms or rehospitalization in the first years after hospitalization, served as the main study criterion. The main result of the meta analysis was that the relapse rate can be reduced by 20 percent if relatives of schizophrenia patients are included in the treatment. If family interventions continued for longer than 3 months, the effect was particularly marked. Furthermore, different types of comprehensive family interventions have similar results. The bifocal approach, which offers psychosocial support to relatives and schizophrenia patients in addition to medical treatment, was clearly superior to the medication-only standard treatment. The effects of family interventions and comprehensive patient interventions were comparable, but the combination did not yield significantly better results than did a treatment approach, which focused on either the patient or the family. This meta-analysis indicates that psychoeducational interventions are essential to schizophrenia treatment. PMID- 11215552 TI - Family support and substance use outcomes for persons with mental illness and substance use disorders. AB - This paper explores the relationship between direct support from family members and friends and substance use outcomes for people with co-occurring severe mental illness and substance use disorders. Data are from a 3-year randomized trial of 203 patients in treatment for dual disorders. Informal (family) caregivers for 174 participants were asked about economic assistance and direct care that they provided to participants. Associations between family support and substance use outcomes were examined with bivariate comparisons of abstainers and nonabstainers and with regression models using change in substance use and cumulative substance use as dependent measures. Family economic support was associated with substance abuse recovery in bivariate and regression analyses. Caregiving hours were significantly associated with substance use reduction but not with cumulative substance use. Informal support was not associated with changes in psychiatric symptoms. The findings suggest that direct family support may help people with dual disorders to reduce or eliminate their substance use. Further research is needed to confirm this connection and to establish the mechanisms by which support is useful. PMID- 11215553 TI - Primary sclerosing cholangitis: challenges of a new millenium. PMID- 11215554 TI - Role of Helicobacter pylori infection in pernicious anaemia. AB - BACKGROUND: Pernicious anaemia is associated with atrophic body gastritis and considered an autoimmune disease. Whether Helicobacter pylori is involved in the induction of pernicious anaemia is uncertain. AIMS: To investigate the prevalence of Helicobacter pylori infection in pernicious anaemia patients and to ascertain whether the Helicobacter pylori-positive patients had distinctive clinical and gastric morphofunctional characteristics. PATIENTS AND METHODS: A series of 81 consecutive pernicious anaemia patients underwent serological, functional and endoscopic/histological investigations. RESULTS: A total of 49 (60.5%) patients were Helicobacter pylori-positive (males 61.2% vs females 38.8%). No difference was observed in clinical and morphofunctional characteristics between Helicobacter pylori-positive and negative patients, whereas distinctive functional/histological features between histologically Helicobacter pylori positive (n=8) and serologically Helicobacter pylori-positive (n=41) cases were detected. In the histologically Helicobacter pylori-positive group, Pepsinogen I was higher [13 (058) vs 5 (0-26) ng/ml; p=0.0025)] and positivity for anti parietal cell antibodies was lower [42.9% vs 76.9, p=0.0867]. Antral histological variables of the gastritis score were significantly higher in the histologically Helicobacter pylori-positive than in the serologically Helicobacter pylori positive patients, but this latter group had a higher score of body atrophy (2.63+/-0.12 vs 1.71+/-0.29; p=0.0051). Body inflammation was also significantly higher in the histologically Helicobacter pylori-positive group (chronic inflammation: 1.43+/-0.2 vs 1.05+/-0.06; p=0.0271; inflammation acitivity: 0. 57+/-0.3 vs 0.15+/-0.06, p=0.0220). Antral mucosa was normal in 24/41 (58.5%) of the serologically Helicobacter pylori-positive patients, but only in 1/8 (12.5%) of the histologically Helicobacter pylori-positive patients (p=0.0232). CONCLUSIONS: Almost two thirds of pernicious anaemia patients have evidence of Helicobacter pylori, but only those with an active Helicobacter pylori infection have distinctive functional and histological features. These findings support the hypothesis that Helicobacter pylori infection could play a triggering role in a subgroup of pernicious anaemia patients. PMID- 11215555 TI - Prevalence of Helicobacter pylori resistance to antibiotics in Northeast Italy: a multicentre study. GISU. Interdisciplinary Group for the Study of Ulcer. AB - AIMS: To evaluate prevalence of primary Helicobacter pylori antibiotic resistances in Northeast Italy and to identify risk factors associated with this resistance. MATERIALS AND METHODS: A total of 248 patients undergoing upper gastrointestinal endoscopy were enrolled from 19 Endoscopy Units over a 6-month period. From each patient, 4 gastric biopsies were taken for histology and 2 were sent to the Central Referral Microbiological Laboratory for culture and determination of antibiotic activity against Helicobacter pylori by means of E test. Strains were considered resistant when minimum inhibitory concentration was >8 microg/ml for metronidazole and >1 microg/ml for clarithromycin. No cut-off value was predefined for amoxycillin. RESULTS: Culture of Helicobacter pylori was successfully performed in 167 patients. Primary resistance to metronidazole, clarithromycin or amoxycillin was 14.9%, 1.8% and 0%, respectively Patients infected with Helicobacter pylori strains resistant to antibiotics were more frequently females than males (70.3% vs 41.4%), had a significantly lower coffee intake (66.6% vs 86.6%) and lower body mass index (23.7+/-2.6 vs 25.3+/-3.6) than patients with susceptible Helicobacter pylori strains. Age, smoking, alcohol use, family history of Helicobacter pylori infection, concomitant diseases and treatments, endoscopic diagnoses, Helicobacter pylori density and histological activity of chronic gastritis were not associated with antibiotic resistance. Multivariate analysis confirmed that female gender (odds ratio = 2.74, 95% confidence interval = 1.03-7.27) was the only significant risk factor associated with antibiotic resistance. CONCLUSIONS: In this population, primary Helicobacter pylori resistance to metronidazole was higher than resistance to clarithromycin, and female gender was significantly associated with this resistance. The low prevalence of resistance to metronidazole, clarithromycin and amoxycillin identified in this geographical area suggests that proton pump inhibitor-based triple regimens including these antibiotics may still be used as first line therapies against Helicobacter pylori infection. PMID- 11215556 TI - Oral nutritional supplementation is effective in the maintenance of remission in Crohn's disease. AB - BACKGROUND: Enteral feeding with either elemental or polymeric diets is an established primary therapy for active Crohn's disease. However, the role of supplementing normal food with elemental diet in the long-term management of Crohn's disease has hitherto not been explored. PATIENTS AND METHODS: A series of 39 consecutive patients with Crohn's disease in clinical remission were studied. Of these, 21 patients (Group 1) received oral nutritional supplementation, taken in addition to their normal diet. Their outcome (relapse rate, Crohn's disease activity index, inflammatory markers) was compared with that of 18 patients (Group 2), who were maintained on a normal unrestricted diet over an observation period of 12 months. RESULTS: A total of 17 patients (81%) tolerated the nutritional supplementation. On an intention-to-treat basis, 10 patients (48%) remained in remission for 12 months, compared to 4/18 (22%) patients in Group 2, p<0.0003. Their Crohn's disease activity index and CRP remained stable while their weight and body mass index improved during the period of nutrition therapy Seven patients in Group 1 and 14 in Group 2 relapsed at a mean of 7.4+/-0.9 and 6.2+/-0.4 months, respectively. The response to nutrition supplement was independent of age, sex, disease duration or location. Four patients (19%) were intolerant to enteral feeding. CONCLUSIONS: Nutritional supplementation is safe, well tolerated and effective in the long-term management of patients with quiescent Crohn's disease. PMID- 11215557 TI - Prevalence of silent coeliac disease in atopics. AB - BACKGROUND: Coeliac disease sometimes runs a subclinical/silent course and is often associated with immunologic and non-immunologic diseases. Although atopy is described as one of the most frequently associated conditions, the prevalence of coeliac disease in atopics has not yet been established. AIM: To evaluate the frequency of coeliac disease in an Italian series of atopics. PATIENTS AND METHODS: Sera from 401 consecutive atopics with no clinical evidence of malabsorption were tested for IgA antiendomysial antibodies by indirect immunofluorescence on human umbilical cord and IgA anti tissue transglutaminase by enzyme-linked immunosorbent assay Results. Four patients (1%) were found to be positive for both autoantibodies. Intestinal biopsy confirmed the diagnosis of active coeliac disease. One of the 4 coeliacs was also affected by Down's syndrome, autoimmune thyroiditis and coeliac hepatitis. In another case, a previously unknown severe iron deficiency was detected. CONCLUSIONS: The present study shows, for the first time, that the prevalence of coeliac disease in atopics is 1%, which is significantly higher than that in the general Italian population. Therefore, atopy should be considered a condition at risk and atopic patients routinely screened by means of specific autoantibody testing. PMID- 11215558 TI - Do we have to screen the general population for coeliac disease instead of only patients with so-called associated diseases? PMID- 11215559 TI - Prognostic indicators of successful endoscopic sclerotherapy for prevention of rebleeding from oesophageal varices in cirrhosis: a long-term cohort study. AB - BACKGROUND: Although band ligation is now recommended for prevention of rebleeding from oesophageal varices in cirrhosis, sclerotherapy is still widely used. Patients submitted to chronic sclerotherapy undergo several endoscopies and experience a large number of serious complications. However, long-term outcome is poorly defined. AIMS: To assess the clinical course and prognostic indicators of patients undergoing chronic sclerotherapy for prevention of variceal rebleeding as a basis for future evaluation of long-term band ligation outcome. METHODS: Prospective cohort study; prognostic analysis by the Cox proportional hazards model. RESULTS: A total of 218 consecutive cirrhotic patients (37 Child class A, 154 B, 27 C) were enrolled in the study Varices were obliterated in 139 (64%) patients in a mean of 5 (+/-2.6) sessions and recurred in 58/139 (41.7%) within one year. A total of 132 (60%) patients experienced 283 rebleeding episodes and 73 (33%) died. Bleeding from oesophageal ulcers was the most serious complication causing 14% of all rebleeding episodes. Significant prognostic indicators of sclerotherapy outcome were: Child-Pugh class for variceal obliteration; gastric varices and platelet count for recurrence of varices; failure to obliterate varices, variceal size and gastric varices for rebleeding; blood urea nitrogen and failure to obliterate varices for death. Presence of gastric varices was the only prognostic indicator for death in the 79 patients not achieving variceal obliteration. A mean of 10 endoscopies and of 6 hospital admissions were needed per each patient with an estimated cost of US dollars 7154 per patient during the first two years of therapy. CONCLUSIONS: Sclerotherapy is a very demanding and costly treatment, and is associated with frequent and serious side-effects. The probability of treatment failure is significantly higher in Child C patients with gastric varices. Alternative treatments should be considered for these patients. PMID- 11215561 TI - Hepatic amyloidosis with light chain deposition disease. A rare association. AB - Monoclonal immunoglobulin deposition diseases are due to pathological protein deposition in various tissues and organs. Protein deposits may be found in a single tissue or systemically and the organs most frequently involved are kidney, heart, peripheral nerves and the liver. Depending on the pattern of the deposits and the type of immunoglobulin, these diseases are distinguished as primary amyloidosis, light chain deposition disease. Differential diagnosis is made in tissue specimens: microscopically by the identification of positive Congo red staining of the deposits, by immunohistochemical demonstration of proteins reacting with light chain (lambda or kappa) antisera or by recognition of fibrillar structures on electron microscopy. We report an unusual case of light chain deposition disease associated with amyloidosis, where hepatomegaly was the presenting manifestation and liver failure the cause of death, without any kidney involvement. PMID- 11215560 TI - A girl with severe fistulizing Crohn's disease. AB - We report the case of a girl with a severe perianal fistulizing Crohn's disease who during intravenous infusion of cyclosporine developed headache, general seizures and cortical blindness. Head magnetic resonance imaging showed spread, cortical-subcortical nonenhancing signal changes. Full neurological recovery was achieved in 24 hours. Cyclosporine was stopped and a single dose of infliximab was infused with rapid improvement of the fistula that at 7 months' follow-up is still closed. PMID- 11215562 TI - Liver transplantation for erythropoietic protoporphyria: report of a case with medium-term follow-up. AB - A case of liver transplantation is described in a 35-year-old male with hepatic failure due to erythropoietic protoporphyria. Data regarding protoporphyrin levels in erythrocytes and faeces, before and after transplantation, seem to indicate that, in this case, protoporphyrin overproduction was, in part, due to liver synthesis. Four years after surgery, the patient is completely free of skin photosensitivity. Liver function tests are normal and there are no significant protoporphyrin deposits in the new liver. However, recurrence of the disease in the long-term cannot be excluded, since erythrocyte protoporphyrin levels have remained elevated after liver transplantation. PMID- 11215563 TI - Granular cell tumour of the oesophagus: a rare cause of dysphagia with differential diagnosis of oesophageal neoplastic lesions. AB - Granular cell tumour is a relatively uncommon, typically benign neoplasm of soft tissue. The macroscopic appearance of oesophageal granular cell tumour is a polypoid lesion, which is often asymptomatic and can be found incidentally, but, in some cases, is symptomatic and requires a correct differential diagnosis with malignant neoplasms of the oesophagus. We describe the case of a 28-year-old female who came to our attention due to a six-month history of heartburn and dysphagia. Oesophagogastroduodenoscopy showed the presence of a polypoid lesion 2 cm above the gastro-oesophageal junction. The overlying mucosa was normal and the lesion seemed to be an isolated submucosal nodule with a "submucosal pill" appearance. It was excised completely using a standard diathermic snare, and diagnosis of oesophageal granular cell tumour was made by histological and immunohistochemical staining. The patient's symptoms disappeared immediately after removal of the nodule by endoscopic polypectomy, and no macroscopic or microscopic recurrence of granular cell tumour was noted during follow-up. Likewise, the patient was symptom-free during follow-up. This case shows that endoscopy is very effective, not only in the diagnosis, but also in the treatment of oesophageal lesions which require careful differential diagnosis. PMID- 11215564 TI - Pathogenesis of colorectal cancer. AB - The development of colorectal cancer has been viewed as an ordered process in which three main phases can be identified: initiation, promotion and progression. There is definite proof that stable alterations of the structure or sequence of DNA (mutations) represent the initiating event; these are followed by an uncontrolled expansion of the neoplastic clones which characterizes tumoural growth. Several classes of genes have been identified foncogenes, tumour suppressor genes and "mutator" genes) the alterations of which are important in the initiation as well as in the promotion and progression of tumours. Colorectal cancer, therefore, results from a series of genetic changes which lead to the progressive and irreversible loss of normal control of cell growth and differentiation. Available evidence is consistent with the hypothesis that there are several molecular pathways underlying the passage from normal mucosa to colorectal carcinoma, thus explaining the existence of intestinal tumours with a different biological nature, which may represent specific targets for prevention and cure. Well-defined molecular pathways have been identified for: A) sporadic colorectal cancer ("Loss of heterozygosity pathway"); B) familial adenomatous polyposis and related polyposis syndromes; C) hereditary non-polyposis colorectal cancer ("mutator genes/microsatellite instability pathway"); D) cancer developing in inflammatory bowel diseases; E) familial colorectal cancer. Thus, there is consistent and considerable evidence suggesting the existence of several biological pathways leading to the same phenotypical expression (i.e., colorectal cancer), and it is likely that additional pathways will be clarified in the future. From a practical point of view, tumours with a diverse biology might offer different and more effective preventive and curative approaches. PMID- 11215565 TI - Occult hepatitis B virus infection. AB - Many studies have shown that hepatitis B virus infection may also occur in hepatitis B surface antigen-negative patients. This occult infection has been identified both in patients with cryptogenic liver disease and in patients with hepatitis C virus-related chronic hepatitis, and much evidence suggests that it may be a risk factor of hepatocellular carcinoma development. However several aspects of this occult infection remain unclear such as its prevalence and the factor(s) involved in the lack of circulating hepatitis B surface antigen. Moreover, it is uncertain whether the occult hepatitis B virus infection may contribute to chronic liver damage, considering that it is usually associated with a suppressed viral replication. Evidence and hypotheses concerning this fascinating field of bio-medical research are reviewed. PMID- 11215566 TI - Muscle paralysis produced by botulinum toxin type A injection in treated torticollis patients compared with toxin naive individuals. AB - We sought to determine whether the response to varying doses of botulinum toxin type A (BTX-A) injected in BTX-A-treated torticollis patients differed from the same injections given in toxin-naive individuals. We have developed a technique to objectively measure muscle weakness resulting from BTX injections in humans and have validated the technique in those not previously treated with BTX. We now examine BTX-A-treated torticollis patients to see if their response to BTX-A injection is similar to that of toxin-naive individuals. We injected 11 torticollis patients who had been receiving BTX-A injections with a standard 5 mouse unit (mu) dose into one extensor digitorum brevis (EDB) muscle and a varying dose into the other EDB, measuring muscle paralysis 2 weeks after the injection. Nine of the 11 patients were clinical and electrophysiologic responders. Two patients were non-responders. In the 9 responding patients the dose response curve to increasing doses of BTX-A was very similar to that seen in toxin-naive individuals. The mean muscle paralysis from the standard 5 mu dose was also similar to that previously reported in toxin-naive individuals. Torticollis patients who continue to respond clinically to BTX-A injections demonstrate essentially the same degree of muscle paralysis from the EDB injections as do subjects who have never been exposed to BTX-A. PMID- 11215567 TI - Inherited myoclonus-dystonia: evidence supporting genetic heterogeneity. AB - Inherited myoclonus-dystonia (IMD) is a new term used to describe an autosomal dominant form of myoclonus. Recently a family with IMD was linked to a region on chromosome 11q23 and a possible mutation identified in the D2 dopamine receptor. We have identified a large family with 12 affected individuals. Using linkage analysis and direct sequencing, the D2 receptor gene was excluded as a cause of myoclonus in this family. These results indicate that the Val154Ile D2 receptor substitution is not the universal cause of IMD. This suggests either that it is a rare, family specific polymorphism not causative of IMD, or that IMD is genetically heterogeneous. PMID- 11215569 TI - Re-emergence of childhood stuttering in Parkinson's disease: a hypothesis. AB - OBJECTIVE: To characterize speech patterns in patients with Parkinson's disease (PD) who have a history of childhood stuttering. BACKGROUND: Childhood stuttering usually resolves, but it re-emerges in some patients after stroke or other brain disorders. This phenomenon of recurrent stuttering has not been characterized in childhood stutterers who later develop PD. METHODS/PATIENTS: Twelve patients with a history of childhood stuttering that remitted and subsequently recurred were included in the study. A structured interview was administered to seven patients, and six were able to answer questions about childhood stuttering. The Johnson Severity Scale (JSS) (range 0-7) and a Situation Avoidance Scale (SAS) were used to rate stuttering severity (range 0-15) and avoidance (range 0-15). RESULTS: The mean age at onset of childhood stuttering was 6.2 years (range 5-10); the mean latency from the onset of childhood stuttering to adult stuttering was 46.1 years; and the stuttering recurred on average 5.9 years (range 0-21) after the onset of PD. The stuttering characteristics in childhood and adulthood included repetitions of sounds and syllables at the beginnings of words, blocks and interjections, physical tension, and a worsening of symptoms with stress. The patients rated themselves as having mild-to-moderate childhood stuttering by the JSS (mean 3.0, range 2-4) and mild-to-moderate stuttering and avoidance by the SAS (mean stuttering score 5.3, range 3-7; mean avoidance score 4.2, range 3-6). There was no apparent association between the severity of childhood stuttering and the severity of PD, but those patients who had higher Unified Parkinson's Disease Rating Scale scores tended to have more and worse symptoms of stuttering. CONCLUSION: Our patients provide evidence for the hypothesis that childhood stuttering may re-emerge in adulthood with the onset of PD. PMID- 11215568 TI - Prevalence of homozygous deletions of the parkin gene in a cohort of patients with sporadic and familial Parkinson's disease. AB - Mutation of the parkin gene is a cause of familial Parkinson's disease of the autosomal recessive form; however, its significance in all Parkinson's disease cases is unclear. Deletions in the parkin gene were found in only 2.2% of 184 Japanese patients with Parkinson's disease. However, deletions were present in 25.0% and 40.0% of the patients with juvenile-onset (< 40 y) and with familiality, respectively. On the other hand, deletions were not found in any adult-onset cases (> 40 y). Half of the patients with parkin gene-related Parkinson's disease lacked both heredity and consanguinity. PMID- 11215570 TI - Stroke and idiopathic Parkinson's disease: does a shortage of dopamine offer protection against stroke? AB - Data on the relationship between idiopathic Parkinson's disease (IPD) and stroke are conflicting. In this study, we examined the frequency of IPD in stroke patients registered in the Maastricht Stroke Registry. With the use of three different search strategies, we found eight individuals with IPD amongst a total of 1,516 stroke patients. We had expected to find approximately 30 IPD patients (relative risk 0.27; 95% confidence interval 0.11-0.53), based on IPD prevalence figures from a Dutch population-based study. We speculate that dopamine deficiency may protect against ischaemic brain damage, perhaps by reducing the effects of excitotoxicity. PMID- 11215571 TI - [123I]beta-CIT SPECT demonstrates decreased brain dopamine and serotonin transporter levels in untreated parkinsonian patients. AB - Striatal dopamine transporters (DATs) and serotonin transporters (SERTs) were evaluated in untreated patients with Parkinson's disease (PD) and controls using single-photon emission computed tomography (SPECT) with 2beta-carboxymethoxy 3beta-(4-iodophenyl)tropane ([123I]beta-CIT). The striatal DAT specific to non displaceable uptake ratios of 29, and the SERT uptake measurements of 27, PD patients were compared with those of 21 and 16 controls, respectively. The results were correlated with Unified Parkinson's Disease Rating Scale (UPDRS) scores, the Hoehn & Yahr stage, age, duration of the disease, and the major PD signs. The specific DAT binding in the caudate, the putamen and the caudate/putamen ratio were measured. In all of the PD patients the striatal uptake values were bilaterally reduced, being 36.9% (P < 0.001) lower than those of the controls. In the hemiparkinsonian patients the reduction was greater on the side contralateral to the initial symptoms (33.3% vs. 27.8%) and the uptake ratios indicated a more pronounced deficit in the putamen (39.1%) than in the caudate (27.9%). The DAT uptake correlated with the UPDRS total score and activities of daily living (ADL) and motor subscores, the Hoehn & Yahr stage, and rigidity score. PD patients had significantly higher caudate to putamen ratios than the controls. In the PD patients the SERT values were lower in the thalamic and frontal regions. The SERT uptake ratio of the frontal area correlated with the UPDRS subscore I. [123I]beta-CIT SPECT provides a useful method for confirming the clinical diagnosis of PD with correlation to disease severity. Additionally, this technique allows the simultaneous measurement of SERT uptake and shows that PD patients, interestingly, seem to have decreased SERT availability in the thalamic and frontal areas. PMID- 11215572 TI - Can peripheral trauma induce dystonia? No! PMID- 11215573 TI - Assessment of plasma lactoferrin in Parkinson's disease. AB - Iron may play an important role in the pathogenesis of Parkinson's disease (PD). Recent studies have shown that the iron-transporting glycoprotein lactoferrin (LF) and its receptor are increased in the substantia nigra (SN) in PD. We investigated whether plasma levels of LF are altered in dopa-responsive PD. Plasma LF was not different between patients with PD (n = 23; 306 +/- 116 [mean +/- standard deviation] ng/ml) and age- and sex-matched healthy control subjects (n = 15; 359 +/- 126 ng/ml ). However, LF was inversely correlated with PD severity (r = -0.68, P = 0.002), an association that remained significant after adjustment for treatment with levodopa, monoaminooxidase inhibitors, and dopa agonists (r = -0.53, P = 0.017). Plasma transferrin and ferritin levels were not different between groups and neither correlated with disease severity nor with LF levels. Together with the result of increased nigral lactoferrin, this finding is compatible with the hypothesis of an imbalance between LF levels in blood and SN in progressing PD. Larger and particularly longitudinal studies and measurements of LF in cerebrospinal fluid are warranted to further examine the role of LF in PD. PMID- 11215574 TI - Clozapine for the treatment of drug-induced psychosis in Parkinson's disease: results of the 12 week open label extension in the PSYCLOPS trial. AB - OBJECTIVE: To report the results of the 12-week, prospective, open label extension of the 4-week, multicenter, placebo-controlled, double-blind PSYCLOPS (PSYchosis and CLOzapine in the treatment of Parkinsonism) trial. This extension examined the chronic safety and efficacy of clozapine in the treatment of drug induced psychosis in Parkinson's disease (PD). BACKGROUND: Psychosis is a serious late complication of PD and may be a harbinger to increased mortality. Clozapine, the first atypical antipsychotic, was shown in several small open label studies to improve psychosis without worsening of motor symptoms. This was recently confirmed in the double-blind PSYCLOPS trial. METHODS: The 53 patients who completed the double-blind portion of PSYCLOPS were evaluated on their original randomized treatment (clozapine or placebo), then had study medication stopped. All were started on clozapine. The patients from both treatment groups were evaluated every 4 weeks over a 12-week period using standardized measures for psychosis and PD. RESULTS: The mean dose of clozapine was 28.78 mg/day. Those originally treated with placebo improved significantly in Brief Psychiatric Rating Scale and clinical global scores for psychosis to the same degree as the group originally randomized to clozapine in the double-blind study. Both groups maintained their response to week 16 (end of the combined double-blind and open label portions). There was no worsening of motor features as measured by the Unified Parkinson's disease rating scale. Eighteen patients were either hospitalized or died during the trial. The most common reasons were pulmonary. CONCLUSIONS: Low-dose clozapine is effective in treating drug-induced psychosis without worsening motor features of PD, and the response is maintained for at least 4 months. Patients with psychosis and PD were previously described as a group with high risk for morbidity and mortality. The high risk continues despite antipsychotic therapy. PMID- 11215576 TI - CSF dopamine, serotonin, and biopterin metabolites in patients with restless legs syndrome. AB - PURPOSE: To evaluate the role of CNS dopaminergic systems in Restless Legs Syndrome (RLS), homovanillic acid (HVA), tetrahydrobiopterin (BH4), and neopterin (NEOP), were assayed in CSF from RLS patients. The serotonin metabolite, 5 hydroxyindoleacetic acid (5-HIAA), was also measured. METHODS: CSF was taken from 16 RLS patients after 2 weeks off medication and from 14 control subjects. The CSF metabolites were determined using HPLC techniques. RESULTS: There was no significant difference in HVA or 5-HIAA, but NEOP and BH4 were higher in RLS patients. The RLS group was significantly older than the control group (64.2 +/- 9.2 years vs. 51.4 +/- 6.3 years; P < 0.001). A multiple regression analysis showed a strong correlation between age and 5-HIAA (r = 0.46, P = 0.04) and between age and NEOP (r = 0.61, P < 0.01). To eliminate the potential error created by the age difference between groups, an age-adjusted subgroup of RLS and control subjects were compared. There was still no difference found for HVA; however, 5-HIAA was now significantly lower (P < 0.01) in the RLS subgroup. Age adjustment eliminated the differences previously found for NEOP, (P = 0.12), but BH4 continued to remain higher in the RLS group (P < 0.01). CONCLUSION: Differences in CSF HVA concentrations were not found. The changes in 5-HIAA and BH4 are of unclear clinical significance and require further assessment with appropriate age-matched controls. PMID- 11215575 TI - Comparison of thalamotomy to deep brain stimulation of the thalamus in essential tremor. AB - OBJECTIVE: To compare outcome in Essential Tremor (ET) patients who have undergone either thalamotomy or Deep Brain Stimulation (DBS) of the thalamus. BACKGROUND: Although both thalamotomy and thalamic DBS are effective surgical treatments of tremor, it is not known if one procedure is superior to the other. DESIGN/METHODS: Thirty-five ET patients underwent thalamotomy between 1994-1998. Data on 18 patients were excluded. The remaining 17 patients were matched for age, sex, side of surgery, and tremor severity to 17 ET patients who underwent thalamic DBS. There were nine men and eight women in each group. The mean age of the thalamotomy group was 74.4 years and that of the thalamic DBS group was 73.1 years. RESULTS: There were no significant differences between any efficacy outcome variables comparing thalamotomy to DBS of the thalamus at baseline or follow-up visits. The surgical complications were higher for the thalamotomy group as compared to the DBS group. However, a larger number of DBS patients underwent repeat surgeries due to problems with the device and the leads. CONCLUSION: Although the efficacy is similar for thalamotomy and DBS of the thalamus for ET, thalamotomy is associated with a higher complication rate. DBS of the thalamus should be the procedure of choice for the surgical treatment of ET in most cases. PMID- 11215577 TI - Kainate acid lesions of the pedunculopontine region in the normal behaving primate. PMID- 11215578 TI - The basal ganglia: part 1 of the MDS-sponsored History of Movement Disorders Exhibit, Barcelona, June 2000. PMID- 11215579 TI - The history of Parkinson's disease: part 2 of the MDS-sponsored History of Movement Disorders Exhibit, Barcelona, June, 2000. PMID- 11215580 TI - Negative myoclonus in posthypoxic patients: historical note. PMID- 11215581 TI - Clinical and genetic studies on familial parkinsonism: the first report on a parkin gene mutation in a Taiwanese family. PMID- 11215582 TI - Hardware failure in parkinsonian patients with chronic subthalamic nucleus stimulation is a medical emergency. PMID- 11215583 TI - Delayed intracerebral electrode infection after bilateral STN implantation for Parkinson's disease. Case report. PMID- 11215584 TI - Bilateral thalamic stimulation for Holmes' tremor caused by unilateral brainstem lesion. PMID- 11215585 TI - Unusual tremor associated with a posterolateral thalamic lesion in a drummer. PMID- 11215586 TI - Task-specific dystonia in a horn player. PMID- 11215587 TI - Acute onset dystonic camptocormia caused by lenticular lesions. PMID- 11215588 TI - Asymmetrical blepharospasm associated with a left frontal cortical infarct. PMID- 11215589 TI - Neuroimaging in basal ganglia disorders: perspectives for transcranial ultrasound. AB - Transcranial sonography is a new diagnostic tool, allowing not only the evaluation of cerebral arteries but also the two-dimensional display of the brain parenchyma. In this review we will summarize basics of the application, the ultrasound anatomy of the brain and sonographic findings in some movement disorders. While in normal adults basal ganglia nuclei are hypoechogenic, they are hyperechogenic in certain basal ganglia disorders. In Parkinson's disease, for example, the substantia nigra can be depicted as a distinctly echogenic area. An elevated echogenicity of the lentiform nuclei was noticed in patients with primary adult-onset dystonia. In both disorders the altered echogenicity may arise from higher heavy metal tissue content (i.e. iron in Parkinson's disease and copper in primary dystonia). Our findings converge to the hypothesis that transcranial ultrasound sensitively detects pathological metal accumulation not identified by other neuroimaging techniques (CT and MRI) and therefore provides new insights in the diagnosis of basal ganglia disorders. The implications of these findings for the understanding of the pathogenesis and its usefulness for the early diagnosis of movement disorders are outlined. PMID- 11215590 TI - Discriminating mild parkinsonism: methods for epidemiological research. AB - Methods for the efficient and accurate detection of parkinsonism are essential for epidemiological studies. We sought to determine whether parkinsonism could be detected by a neurologist from a videotaped assessment and whether neurobehavioral methods (motor, cognitive, and sensory) discriminated between patients with Parkinson's disease (PD) and controls. Fifteen patients with mild PD (Hoehn and Yahr I-III) were compared to 15 age-, sex-, and education- matched controls. Each participant underwent a videotaped neurological examination (based on the Unified Parkinson's Disease Rating Scale, UPDRS), administered by a trained technician, and reviewed by a neurologist, as well as a series of neurobehavioral tests. The neurologist identified PD patients with 86% sensitivity and 100% specificity. Among the neurobehavioral tests, finger tapping, combined with one or more among olfaction, visual contrast sensitivity, or Paired Associates Learning, correctly classified 90%, or more, of subjects. Individual psychological tests did not discriminate reliably between groups. We conclude that videotaped assessments of parkinsonism or objective tests of motor and sensory function can accurately detect patients with PD. Both approaches have potential for identifying PD cases, but the latter may be more efficient for screening. PMID- 11215591 TI - Loss of olfaction in de novo and treated Parkinson's disease: possible implications for early diagnosis. AB - Olfactory dysfunction is a common finding in patients with Parkinson's disease (PD). As most studies reported on odor identification in more advanced and treated PD, we administered an odor detection, discrimination, and identification test to a heterogeneous, partly de novo, group of patients. Forty-one non demented PD patients, 24 of whom had untreated early PD, and 18 healthy controls, were examined. Odor identification and discrimination data were corrected for odor detection scores. PD patients scored significantly lower on all olfactory tests. Interestingly, the subgroup of de novo patients with early PD also showed significant olfactory disturbances compared with healthy subjects. Within the PD group, using multiple regression analysis, we found a significant, negative correlation between odor discrimination measures and disease The present study is the first to describe decreased performance of PD patients on odor discrimination, in addition to the already well-established deficits in odor detection and identification. Furthermore, odor discrimination measures were related to disease severity, possibly indicating that at least some aspects of olfactory dysfunction in PD may be secondary to ongoing degenerative processes in PD. As significant olfactory impairments were found in early, de novo PD, olfactory tests may be useful in the early diagnosis of PD. PMID- 11215592 TI - The relation between EMG activity and kinematic parameters strongly supports a role of the action tremor in parkinsonian bradykinesia. AB - The kinematics characteristics of an upper arm extension of large amplitude (90 degrees) performed in the horizontal plane and the simultaneous activity of the shoulder muscles were recorded in 12 parkinsonian patients and in six normal control subjects. The movement, triggered by an acoustic "go" signal, was preceded by an isometric adduction. Within the whole population of individuals (n = 18) a strong, positive correlation was observed between the root mean square value of agonist EMG activity, evaluated during the acceleration phase of the movement, and both peak velocity and acceleration. In six patients tremor bursts at the frequency of 8-14 Hz (action tremor) were observed during the movement phase in the anterior, middle, and posterior deltoid: all these patients showed low root mean square values and were bradykinetic with respect to the control subjects. The remaining six patients did not show this action tremor during the movement phase. All but one had an agonist activation of normal duration and amplitude, showed high root mean square values, and performed well in the range of control subjects. We conclude that the inability to suppress the activity of pathological oscillator(s) responsible for the action tremor plays a fundamental role in the bradykinesia associated with Parkinson's disease. PMID- 11215593 TI - Accelerometric assessment of levodopa-induced dyskinesias in Parkinson's disease. AB - Our objective was to develop parameters for objective ambulatory measurements of levodopa-induced dyskinesias (LID) in patients with Parkinson's disease (PD). Twenty-three PD patients with mild to severe LID were submitted to a standardized protocol of 1-minute recordings during rest, talking, stress, and four activities of daily life (ADL). Patients were simultaneously monitored with portable multi channel accelerometry (four pairs of bi-axial sensors mounted onto the most affected arm, leg, and at the trunk) and recorded by video. LID severity was assessed with a modified Abnormal Involuntary Movement Scale (m-AIMS). The signals were analyzed, and every 1/8-second interval the amplitude was obtained of the dominant frequency within 1-4 Hz and 4-8 Hz frequency bands (Amp1-4 and Amp4-8). For both measures, convergent validity, reproducibility, and responsiveness were determined. In absence of voluntary movements, a significant relation was found between Amp1-4 and Amp4-8 and m-AIMS. Repeated measurements during rest showed a high reproducibility (intraclass correlation coefficient = 0.90 [Amp1-4] and 0.86 [Amp4-8]). The extent to which LID increased with talking and stress correlated significantly (p = 0.02) between the objective and clinical measures (intraclass correlation for differences = 0.67). During ADL, LID occurred in a similar frequency band as voluntary movements and only Amp1-4 and Amp4-8 of the trunk and leg sensor remained highly correlated with m-AIMS. Although objective measures of LID are reliable and responsive, they fail to distinguish LID from voluntary movements. These measures are of value only when obtained during rest (all sensor sites) or during ADL when derived from those body segments that are normally not involved in these ADL tasks (trunk and leg). PMID- 11215594 TI - The auditory startle reaction in parkinsonian disorders. AB - The auditory startle reaction to an unexpected loud stimulus is regarded as a brainstem reflex originating in the nucleus reticularis pontis caudalis and being distributed up the brainstem and down the spinal cord along slowly conducting pathways. Auditory startle responses (ASR) have been reported absent or reduced in progressive supranuclear palsy (PSP), and delayed in Parkinson's disease (PD), but normal in multiple-system atrophy (MSA). For the first time we studied ASR in patients fulfilling the clinical criteria of dementia with Lewy bodies (DLB) (n = 8), a neurodegenerative disorder characterized by cortical and subcortical depositions of Lewy bodies resulting in parkinsonism and progressive cognitive decline. For comparison, we also investigated patients with PD (n = 10), MSA (n = 7), PSP (n = 10), and age-matched healthy controls (n = 10). ASR were elicited by binaural high-intensity auditory stimuli. Surface electromyographic activity was simultaneously recorded from facial, upper, and lower extremity muscles. For each muscle, we assessed response probability and measured latency, amplitude, duration, and habituation rate. Patients with DLB had fewer and abnormally delayed ASR of low amplitude and short duration in extremity muscles compared to healthy controls. Furthermore, we confirm and extend previous findings of abnormal ASR in PSP and PD, and also demonstrate exaggerated ASR in extremity muscles of MSA patients. The different patterns of ASR abnormalities may reflect distinct types of brainstem dysfunction in DLB. PMID- 11215595 TI - Can peripheral trauma induce dystonia and other movement disorders? Yes! PMID- 11215596 TI - Dorsal subthalamotomy for Parkinson's disease. AB - We report our experience of unilateral subthalamotomy in patients with Parkinson's disease (PD). Eleven patients were included in a pilot, open-labeled study to assess the effect of unilateral lesion of the subthalamic nucleus (STN) with a minimum of 12 months of follow-up. The guidelines of CAPIT (Core Assessment Program for Intracerebral Transplantation) were followed for recruitment into the study and follow-up assessment. Levodopa equivalents daily intake (mean 967 mg) were unchanged during the first 12 months in all but one patient who stopped medication. The sensorimotor region of the STN was defined by semimicrorecording and stimulation and a thermolytic lesion was placed accordingly. There was a significant reduction in both UPDRS parts II and III in the "off" state at 1-, 6-, and 12-month follow-up. This effect was maintained in four patients up to 24 months. The dyskinesia score did not change postoperatively. Lesion-induced dyskinesias were not a management problem except in one patient who developed a large infarction several days postsurgery. This initial study indicates that a lesion of the STN is not generally associated with hemiballismus in PD. Subthalamotomy may induce considerable motor benefit and could become another surgical option under specific circumstances. PMID- 11215597 TI - Changes in vocal loudness following intensive voice treatment (LSVT) in individuals with Parkinson's disease: a comparison with untreated patients and normal age-matched controls. AB - This study assessed the impact of the Lee Silverman Voice Treatment (LSVT) on vocal loudness [sound pressure level (SPL)] in a group of dysarthric individuals with idiopathic Parkinson's disease (IPD). Pre- to post-treatment changes in SPL in the treated group were compared with changes in voice SPL during the same time in two control groups: individuals with IPD not treated with the LSVT and in non disordered individuals, age-matched to the patients. All subjects produced the same voice and speech tasks--sustaining vowel phonation, reading the "Rainbow Passage," producing a short monologue, and describing a picture. These tasks were recorded at three different occasions: just prior to treatment, just after treatment, and 6 months following treatment. The individuals treated with LSVT increased voice SPL from baseline to post-treatment by an average of 8 dB and from baseline to 6 months follow-up by an average of 6 dB. These changes were statistically significant and perceptibly audible. No significant changes in SPL were observed in the control groups during the time corresponding to the treatment and follow-up. Differences in SPL between the treated and untreated patients at post-treatment and follow-up were statistically significant for all voice and speech tasks. These findings, along with others, provide additional support for the efficacy of the LSVT. PMID- 11215598 TI - Suppression of harmaline-induced tremor in rats by vagus nerve stimulation. AB - We studied whether vagus nerve stimulation could suppress tremor in the harmaline tremor model in the rat. Animals were chronically implanted with helical leads around the left vagus nerve and a disk-shaped electrode positioned subcutaneously in the dorsal neck. Harmaline-induced tremor was recorded on a physiograph while each animal received a sequence of five 20-minute trials. Each trial consisted of five minutes of pre-stimulation baseline, five minutes of vagus nerve stimulation, and ten minutes of post-stimulation. Vagus nerve stimulation significantly suppressed harmaline-induced tremor. The suppressive effect was present within the first minute of stimulation and was reproducible across the five trials of the study. The results of this study suggest that the central generator or expression of tremor in the harmaline animal model can be suppressed by vagus nerve stimulation. PMID- 11215599 TI - A teaching videotape for the assessment of essential tremor. AB - Teaching videotapes, developed to aid in the evaluation of several movement disorders, have not been used in essential tremor research. As part of the Washington Heights-Inwood Genetic Study of Essential Tremor (WHIGET), we developed a reliable and valid tremor rating scale. Because this rating scale is currently being used by investigators at other centers, we developed a teaching videotape to aid in the consistent application of this scale. OBJECTIVE: To develop a teaching videotape for a revised version of the WHIGET Tremor Rating Scale and to assess the interrater agreement among raters who used this videotape to rate tremor. METHODS: The revised WHIGET Tremor Rating Scale was used to rate action tremor from 0 to 4 during six tests: arm extension, pouring, drinking, using a spoon, finger-to-nose, and drawing spirals. A 22-minute teaching videotape was developed that includes a 29-item educational section and a self assessment section consisting of 20 examples of tremor ratings chosen by the two WHIGET study neurologists. Eight raters, including senior movement disorder specialists, movement disorder fellows, general neurologists, and a movement disorder nurse practitioner, independently viewed the videotape and rated tremor during the self-assessment section. Interobserver reliability was assessed with weighted kappa statistics (kappa(w)). RESULTS: Eight raters each rated 20 items (160 ratings total). Total kappa(w) was 0.97 (nearly perfect agreement). Interrater reliability was as follows: kappa(w) = 0.99 (movement disorder specialists), kappa(w) = 0.98 (movement disorder fellows), and kappa(w) = 0.97 (general neurologists); all kappa(w) were nearly perfect. CONCLUSIONS: This teaching videotape may be used to improve the uniform application of the revised WHIGET Tremor Rating Scale by raters with various levels of experience in movement disorders. PMID- 11215600 TI - Abnormalities of spatial and temporal sensory discrimination in writer's cramp. AB - Clinical observations of patients with writer's cramp suggest that abnormalities of the sensory system may be a frequent finding in this disorder. Neurophysiological data from an animal model of focal dystonia have revealed cells in somatosensory cortex with enlarged and overlapping tactile receptive fields. However, psychophysical studies so far have been unable to document a clinical correlate supporting a similar enlargement of receptive fields in humans. We compared the fingertip discrimination of the orientation of fine spatial gratings between writer's cramp and control subjects and found a significant decrease in grating sensitivity in the patients, consistent with the possibility of enlarged tactile receptive fields. In addition, we duplicated previous experiments showing an abnormality of tactile temporal discrimination. The results provide psychophysical measures which may relate to the development of sensory cortical reorganization in patients with writer's cramp. PMID- 11215601 TI - Disinfection efficacy of contact lens care solutions against ocular pathogens. AB - PURPOSE: Three commercially available products labeled as multi-purpose contact lens solutions, one multi-purpose disinfecting solution, and a hydrogen peroxide system were evaluated for antimicrobial activity according to the current International Organization for Standardization (ISO) and the U.S. Food and Drug Administration (FDA) stand-alone procedure for disinfecting products. One multi purpose solution was selected to assess its antimicrobial activity against two human corneal isolates of Pseudomonas aeruginosa. METHODS: Products were challenged with bacteria and fungi, and following a specified period, aliquots of inoculated test solution were neutralized and plated on validated recovery media. After incubation the number of viable microorganisms was enumerated and mean log reductions determined. RESULTS: ReNu MultiPlus (Bausch & Lomb, Rochester, NY), AOSEPT (CIBA Vision Corporation, Duluth, GA), and Opti-Free Express with Aldox (Alcon Laboratories, Ft. Worth, TX) were the only lens care products that met the stand-alone criteria for all required microorganisms within their minimum recommended disinfection time. Of these, ReNu MultiPlus provided the greatest overall antimicrobial activity. ReNu MultiPlus demonstrated a significantly higher mean log reduction of Staphylococcus aureus and Serratia marcescens than Opti-Free Express. ReNu MultiPlus also gave a higher mean log reduction of S. aureus and S. marcescens than AOSEPT, and a higher mean log reduction of Candida albicans and Fusarium solani than AOSEPT, Complete Comfort Plus (Allergan, Irivine, CA), and Solo-Care (CIBA Vision Corp.) (at 4 hours). Both Complete Comfort Plus and Solo-Care (at 4 hours) met the primary acceptance criteria for bacteria; however, neither product possessed enough antimicrobial activity to meet the minimum criteria for yeast or mold. ReNu Multiplus was effective against corneal isolates of P. aeruginosa. CONCLUSION: ReNu MultiPlus, AOSEPT, and Opti Free Express met the requirements of the stand-alone primary criteria for disinfecting solutions. ReNu MultiPlus demonstrated the greatest overall disinfection efficacy, as well as excellent activity against clinical strains of P. aeruginosa. PMID- 11215602 TI - Evaluation of the spectral transmittance of UV-absorbing disposable contact lenses. AB - PURPOSE: Increasing evidence suggesting deleterious effects of ultraviolet radiation (UVR) on the eye has prompted manufacturers to develop UV-absorbing disposable contact lenses. The spectral transmittances of a sample of these lenses were measured in order to determine if they provide adequate protection from UVR. METHODS: Four types of UV-absorbing disposable lenses were studied (Acuvue [Vistakon, Jacksonville, FL], Precision UV [Wesley-Jessen, Des Plaines, IL], Specialty Sport [Specialty UltraVision, Sunnyvale, CA], and Surevue [Vistakon]). For comparison, a lens without UV-absorbing properties (Acuvue), a conventional soft lens (Permaflex UV [Cooper Vision, San Jose, CA]) and an RGP lens (Boston ES [Polymer Technology, Rochester, NY]) were also evaluated. The tested lens was placed in a silica wet cell filled with saline. Spectral transmittance was measured over the 200-800 nm waveband. RESULTS: Each disposable lens exhibited a transmittance window in the 240-320 nm waveband. Computing indices of protection factor and safe exposure duration allowed for the assessment of the level of protection afforded by each lens. Among disposable lenses studied, the Surevue performed best with a transmittance of less than 1% in the waveband 280-348 nm and the longest safe exposure duration, while the Specialty Sport had the highesttransmittance of UVB (290-315 nm). CONCLUSION: All UV-absorbing lenses studied provided a better level of protection from UVR exposure than lenses without UV absorber. These results will help the eyecare practitioner in prescribing the most appropriate UV-blocking lens for each patient. PMID- 11215603 TI - Bacterial populations on 30-night extended wear silicone hydrogel lenses. AB - PURPOSE: Ocular infection and inflammation during hydrogel lens extended wear is often associated with colonization of the lenses with bacteria. This study compares colonization of a high Dk silicone hydrogel contact lens (lotrafilcon A) worn on a 30-night extended wear basis to a low Dk HEMA-based lens (etafilcon A) worn on a 6-night extended wear schedule. METHODS: The group wearing the low Dk/t soft contact lens (n = 63) replaced their lenses weekly and the group wearing high Dk/t soft contact lenses replaced their lenses monthly (n = 64). Lens allocation was assigned randomly at enrollment. Worn lenses, from one eye only, were collected aseptically and placed in sterile vials. Microbial growth on various media was enumerated and the number of colony forming units (cfu) per lens was calculated in categories of normal ocular microbiota (such as coagulase negative staphylococci and Propionibacterium spp.) and known ocular pathogens (such as Staphylococcus aureus and gram-negative bacteria). The proportion of samples colonized with these bacteria and the extent of colonization were compared between the two groups. The proportion of sterile lenses was calculated, and the types of bacteria on each lens group were compared. RESULTS: No differences between the low and high Dk/t Soft contact lens groups were observed in the proportion of lenses colonized by Propionibacterium spp. (48% vs 43%, P = 0.4) or coagulase-negative staphylococci (47% vs 54%, P = 0.2). Similarly, no differences were found for lenses colonized by S. aureus (0% vs 2%, P = 0.1) or gram-negative bacteria (3% vs 2%, P = 0.8). The types of bacteria isolated from the high and low Dk/t lenses were similar. There were no differences in the number of sterile samples (28% vs 27%, P = 0.8) from each group. CONCLUSIONS: These findings suggest that high Dk/t silicone hydrogel materials are colonized by similar numbers and types of microorganisms during extended wear compared to HEMA-based material. Most lenses were colonized by commensal bacteria during 30 night extended wear with high Dk/t lenses and during 6-night extended wear with low Dk/t lenses. The incidence of sterile samples was the same between the high and low Dk/t soft contact lens groups. PMID- 11215604 TI - Conjunctival histologic findings of dry eye and non-dry eye contact lens wearing subjects. AB - PURPOSE: To determine if contact lens wearers with dry eye (DE CL) have greater histological and inflammatory conjunctival epithelial changes compared to non-dry eye contact lens wearers (CL). METHODS: Fifty-eight myopic subjects were recruited for the study: DE CL group (N=27), CL group (N=11), and control group (N=20). Contact lens groups were matched for proportions of rigid gas permeable (RGP) lenses, disposables, and conventional soft contact lenses. Dry eye was defined by McMonnies dry eye symptom survey score of > or =14, fluorescein break up time (FBUT) of <10 seconds, and the presence of rose bengal staining. Ocular surface samples were taken using conjunctival impression cytology to determine nucleo-cytoplasm ratio, goblet cell density (GCD), and expression of conjunctival antigens to HLA DR and CD23. RESULTS: HLA DR and CD23 expression were significantly greater for the DE CL group compared to the CL group (P=0.0122 and P=0.0072, respectively). The CL group had a significant reduction in GCD (P=0.0001), and greater expression of ocular surface antigens to HLA DR (P=0.04) and CD23 (P=0.04) compared to the control group. CONCLUSIONS: The results of this study support the view that mechanical influences are responsible for the conjunctival squamous metaplasia changes in contact lens wear. Dry eye in contact lens wear is associated with allergic and immune mediated inflammatory processes. PMID- 11215605 TI - Practical experience with a high Dk lotrafilcon A fluorosilicone hydrogel extended wear contact lens in Spain. AB - PURPOSE: Several research studies on high Dk soft contact lens materials have been published, but little has been reported from practical clinical experience with these new materials. This study reports in-practice clinical experience with the lotrafilcon A fluorosilicone hydrogel material from a 6-month study in Spain. METHODS: Eighty-five patients were dispensed lotrafilcon A lenses (Focuse NIGHT & DAY [CIBA Vision Corporation]) for monthly replacement by 13 investigators from eight practices. The recommended wear schedule was daily wear for the first week and then up to 6-night extended wear through the first month and up to 30-night extended wear through 6 months. Follow-up visits were at 1 week, 1 month, 3 months, and 6 months. Clinical and patient subjective data were collected at each visit. RESULTS: Among patients who continued in the study at each visit, Snellen visual acuity (VA) of 20/25 or better was achieved by at least 96% of all eyes at all visits; lens surfaces assessments for front surface deposits, front surface wetting, and back surface debris averaged less than grade 1 (0-4 scale) for all lenses at all visits; biomicroscopy grades averaged well below grade 1 (0-4 scale) for all eyes at all visits; acceptable or optimal fit was assessed for 97% or more of all lenses at all visits. These patients rated the average overall comfort, vision, and handling above 9 (0-10 scale) at 6 months and 98% reported satisfaction with the lenses at 6 months. Eighty-two percent of patients dispensed completed the study. Seven patients were discontinued because of fit, and seven were discontinued because of positive biomicroscopy signs. CONCLUSIONS: The lotrafilcon A lens performed well clinically and it was accepted well by patients, with most practitioners recommending and most patients wearing it for up to 30 nights extended wear. Practitioners should be attentive to fit and discomfort complaints at dispensing and follow-up and may want to recommend lubricating or rewetting drops for those patients with dryness symptoms. PMID- 11215606 TI - Microbiological profile of a shipboard environment and the flora on contact lenses of seamen. AB - PURPOSE: The purpose of this study was to culture and identify the spectrum of organisms (and their sensitivities) that contaminate the extended wear contact lenses of seamen in their working environment. A secondary aim was to identify the most appropriate first-line antibiotic regimen to be used on seamen who sustain contact lens-related corneal keratitis on board ship. METHODS: Twenty pairs of contact lenses of 20 seamen in one group and 24 pairs in another group wearing contact lenses were collected at the end of 1 week of extended wear. Groups one and two differed only in the way lenses were stored prior to culturing. All contact lenses were then brought to the microbiological lab within 24 hours for culture and sensitivity testing. RESULTS: The most common contaminants on the contact lenses in this study were Staphylococcus epidermidis and Staphylococcus aureus, organisms resident on the normal eyelids. Enterobacterand Pseudomonas species, present in a shipboard environment, were also identified as contaminants on the contact lenses. The organisms cultured from the contact lenses correlated well with those of normal lid flora as well as from the ship environment and are probably derived from these sources. Storage in saline-containing preservatives yielded significantly less positive bacterial cultures from the contact lenses in our study. All bacterial isolates were sensitive to ciprofloxacin whereas several bacteria resistant to cefazolin and gentamicin were identified. CONCLUSION: The most common contaminants on the contact lenses in this study were Staphylococcus epidermidis and Staphylococcus aureus, organisms resident on the normal eyelids. Enterobacter and Pseudomonas species, which are normally present in a shipboard environment, were also identified as contaminants on the contact lenses. Ciprofloxacin is effective against all organisms identified as contaminants on the contact lenses in this study. Of all the antibiotics tested, it is probably the most suitable agent against contact lensrelated keratitis under such shipboard circumstances and is thus recommended in these situations. PMID- 11215607 TI - Diagnosis of hemophilia made after intraoperative bleeding during attempted penetrating keratoplasty in an elderly patient. AB - PURPOSE: To report an unusual case where the diagnosis of hemophilia was made after attempted penetrating keratoplasty in an elderly patient. METHODS: A 75 year old white male with a full-thickness corneal scar in the visual axis and a visually significant cataract OD was to undergo penetrating keratoplasty and cataract extraction with lens implantation for visual rehabilitation. There was no history of bleeding diathesis given. RESULTS: During placement of the Flieringa ring, a progressively enlarging 360 degrees subconjunctival hemorrhage was observed. Given the unusual bleeding,the procedure was aborted and the patientwas referred to the hematology service for further evaluation. Laboratory studies revealed a diagnosis of atypical hemophilia of mild severity. CONCLUSIONS: The initial diagnosis of hemophilia in any elderly patient is unusual. This case is even more unusual asthe diagnosis of a bleeding disorder was first considered after excessive subconjunctival hemorrhage developed during attempted penetrating keratoplasty. PMID- 11215608 TI - Comamonas acidovorans keratitis in a hydrogel contact lens wearer. AB - PURPOSE: To present an unusual case of keratitis in a patient who wears hydrogel contact lenses that are replaced on a monthly basis. The agent isolated was Comamonas acidovorans, a species of Pseudomonas. METHODS AND RESULTS: A 40-year old patient who wears hydrogel contact lenses that are replaced on a monthly basis presented with a red eye. The patient reported that the eye had been red for 2 days. A peripheral corneal stromal infiltrate was found and Comamonas acidovorans was isolated in culture. The patient was initially treated with high dose gentamicin. After the results of cultures and sensitivity studies were obtained, she was given ciprofloxacin, leading to the remission of the case. CONCLUSIONS: Comamonas acidovorans should be considered as a possible agent of keratitis in hydrogel contact lens wearers-a culture and sensitivity studies may be indicated. PMID- 11215609 TI - Contact lenses, refractive surgery, and spectacles: competing modalities or something else? PMID- 11215610 TI - Macroscopic water deposits on polycrystalline gold measured by scanning force microscopy. AB - Data of water adsorption on polycrystalline gold show the formation of a multilayer film of several nanometers with the increase of relative humidity. We have measured this adsorption process by scanning force microscopy in both dynamic and jumping modes. We find interesting differences in the adsorption of water on the terraces and at grain boundaries. Measurements of adhesion force are also reported. PMID- 11215611 TI - Quantification of red blood cells using atomic force microscopy. AB - For humans the sizes and shapes of their red blood cells are important indicators of well being. In this study, the feasibility of using the atomic force microscope (AFM) to provide the sizes and shapes of red blood cells has been investigated. An immobilisation procedure has been developed that enabled red blood cells to be reliably imaged by contact AFM in air. The shapes of the red blood cells were readily apparent in the AFM images. Various cell quantification parameters were investigated, including thickness, width, surface area and volume. Excellent correlation was found between the AFM-derived immobilised mean cell volume (IMCV) parameter and the mean cell volume (MCV) parameter used in current haematological practice. The correlation between MCV and IMCV values has validated the immobilisation procedure by demonstrating that the significant cell shrinkage that occurs during immobilisation and drying does not introduce quantification artifacts. Reliable IMCV values were obtained by quantifying 100 red blood cells and this typically required 3-5 AFM images of 100 microm x 100 microm area. This work has demonstrated that the AFM can provide in a single test the red blood cell size and shape data needed in the assessment of human health. PMID- 11215612 TI - Investigation by atomic force microscopy of forces at the origin of cement cohesion. AB - In cement paste, the cohesion results of the interactions between calcium silicate hydrate (CSH) surfaces in an interstitial ionic solution. (N, V, T) Monte Carlo simulations show that the interactions are due to the ion correlation forces influenced by the surface charge density, the ionic concentration and the ion valence. This paper deals with the direct measurement in solutions by atomic force microscopy (AFM) of the forces and the interaction ranges between a probe and an atomically smooth substrate covered by CSH nanoparticles. Different electrolytic solutions (Ca(OH)2, CaCl2, NaCl, NaOH) have been used in order to determine influent parameters permitting to identify the nature of acting forces. Investigations have been rendered possible by selecting appropriate experimental setup and solutions. The selected probe and substrate on which CSH nanoparticles have previously grown are neutral regarding the reactivity during experiments permitting the exchange of solutions. Results show that a force originates from electrostatic nature and differs from Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. Agreement is found between experiments and (N,V,T) Monte Carlo simulations of ionic correlation forces. These forces are at the origin of the cohesion of cement paste. PMID- 11215613 TI - Probing molecular interactions and mechanical properties of microbial cell surfaces by atomic force microscopy. AB - Knowledge of the surface properties of microbial cells is a key to gain a detailed understanding of their functions in the natural environment and to efficiently exploit them in biotechnological processes. In this paper, we present force-distance curves recorded, by atomic force microscopy (AFM) in aqueous solutions, on various microbial samples: reconstituted S-layers, whole fungal spores and several bacterial strains. The approach and retraction curves exhibited important differences--depending on the type of microorganism, on the physiological state (dormancy versus germination) and on the environmental conditions (ionic strength)--which were shown to reflect differences in long range surface forces, adhesion forces and mechanical properties. These data illustrate the great potential of AFM force measurements to elucidate the physical properties of microbial cells and to understand, at the molecular level, biointerfacial phenomena such as cell adhesion and cell aggregation. PMID- 11215614 TI - Comparative studies of bacteria with an atomic force microscopy operating in different modes. AB - Escherichia coli bacterial cells of two strains JM109 and K12 J62 were imaged with atomic force microscopy (AFM) in different environmental conditions. The AFM results show that the two strains have considerable difference in the surface morphology. At the same time after rehydration both strains show the loss of the topographic features and increase in lateral and vertical dimensions. Results obtained in different AFM modes (contact, tapping, MAC) were compared. Imaging in culture medium was applied for direct observation of the surface degradation effect of lysozyme. The treatment of the cells with the enzyme in the culture medium lead to the loss of surface rigidity and eventually to dramatic changes of the bacteria shape. PMID- 11215616 TI - Spin-column isolation of DNA-protein interactions from complex protein mixtures for AFM imaging. AB - Applications of atomic force microscopy (AFM) to investigate structural functional interactions between DNA and proteins, at the molecular level, should prove valuable for gaining a better understanding of gene expression. Specific genomic DNA-protein interactions occur within a sea of intracellular proteins. Successful AFM imaging requires isolating the specific DNA-protein complex free of background protein contamination. Using spin-column chromatography, we report the successful isolation and AFM imaging of transcription factor DNA complexes from DNA molecules incubated with crude cell lysates. This method should be applicable for the isolation and imaging of other specific DNA-protein complexes pertinent to functional genomic research. PMID- 11215615 TI - Recognition force microscopy/spectroscopy of ion channels: applications to the skeletal muscle Ca2+ release channel (RYR1). AB - The skeletal muscle Ca2+ release channel (ryanodine receptor 1, RYR1) plays an important role in the excitation-contraction coupling process. We purified ryanodine receptor type 1 from rabbit white muscle and adsorbed it to mica sheets with the cytoplasmic side facing up. Single receptors of uniformly distributed size and shape of 10-12 nm height and 40-50 nm width, and occasionally some aggregates were seen in contact mode AFM images. These immobilized RYR1 were specifically recognized by rabbit anti-RYR1 (antibody#8) with at least 30% efficiency, as measured by an enzyme immunoassay with goat-anti-rabbit. Single specific antibody-antigen recognition events were detected with AFM tips to which an antibody#8 was tethered. In linear scans, the occurrence of antibody-antigen binding showed significant lateral dependence, which allowed for the localization of binding sites with nm resolution. Variation of the loading rate in force spectroscopy experiments revealed a logarithmic dependence of the unbinding forces, ranging from 42 to 73 pN. From this dependence, a bond width of the binding pocket of L = 0.2 nm and a kinetic off-rate of koff = 12.7s(-1) was determined. PMID- 11215617 TI - The scanning near-field optical microscope as a tool for proteomics. AB - The identification of the entire genetic code of human DNA is more or less completed. With this knowledge, research in identifying the real information lying in the genes, will begin. This information is contained in the proteins, which are the main biological actors in the cell. For this reason proteins will be targeted in biological investigations in the future. The structure, affinity and reactivity of each identified protein has to be determined, which is a primary goal in the field of proteomics. This will require new and better strategies to identify protein-protein interaction. Our approach, based on the detection and visualization of single proteins by scanning near-field optical microscopy (SNOM), has allowed us to visualize various fixed and fluorochrome labelled proteins at the nanometer scale. Subsequently SNOM may then be developed to efficiently detect the specific behavior of a certain protein in response to other biomolecules. PMID- 11215618 TI - Temperature dependence of the topology of supported dimirystoyl-distearoyl phosphatidylcholine bilayers. AB - Topology of fluid and gel domains in the supported bilayer two-component system formed from equimolar mixtures of dimyristoylphosphatidylcholine (DMPC) and distearoylphosphatidylcholine (DSPC) was determined by AFM, at various temperatures corresponding to the gel and the gel + fluid region of the phase diagram. The data show that, in the disconnected fluid part of the DMPC/DSPC gel liquid crystal-phase-separation region, the size of fluid domains markedly exceeds that predicted from spectroscopic experiments or from Monte Carlo simulations. They provide a direct evidence for the transition from the disconnected fluid to the disconnected gel region of the phase diagram, again with gel-phase domains much larger than expected. Finally, images of the gel phase at different temperatures suggest that structural rearrangements of the phospholipids can disrupt the continuity of the supported bilayer. PMID- 11215619 TI - Analysis of protein crystal growth at molecular resolution by atomic force microscopy. AB - High-resolution atomic force microscopy (AFM) studies have been performed to analyze the molecularity of growth steps of the (1 1 0) face of tetragonal lysozyme crystals. Besides a major population of step heights of about 5.5 nm also step heights of about half this size were observed. The latter steps always appeared pairwise. Both surfaces the 1 1 0) face and the (1 0 1) face could be imaged at molecular level. Comparison of the height pattern of the corresponding surface structure indicates that the (1 1 0) face is relatively smooth of less than 0.2 nm compared to the (1 0 1) face of about 1.5 nm. AFM linescan images of the (1 0 1) face indicate the insertion of lysozyme aggregates in solution to the crystal surface rather than lysozyme monomers. This study suggests that insertion of lysozyme aggregates in the solution yields growth steps of the (1 1 0) face of monomolecular as well as of bimolecular unit height. PMID- 11215621 TI - Measuring magnetic susceptibilities of nanogram quantities of materials using microcantilevers. AB - We describe a novel technique for measuring magnetic susceptibilities of nanogram quantities of magnetic materials that utilizes the extreme force sensitivity of microcantilevers. The magnetic force acting on samples attached to the free end of a cantilever can be measured as changes in the resonance response of the cantilever. The shift in resonance frequency of the cantilever is proportional to the field gradient, whereas the deflection of a cantilever is proportional to the magnetic force. The magnetic susceptibility measurement is based on comparison of the forces acting on the sample and a reference material in the same magnetic field and field gradient. We have determined the magnetic susceptibilities of nanogram quantities of many paramagnetic materials. The measured magnetic susceptibilities show excellent agreement with values found in the literature. PMID- 11215620 TI - Chemical sensors and biosensors in liquid environment based on microcantilevers with amplified quality factor. AB - A new technique is presented for bio/chemical sensors, based on microcantilevers, for detection in liquid environment. The low quality factor of the cantilever in liquid is increased up to three orders of magnitude by using Q-control. This enables AC detection that is immune to the long-term drift of the DC cantilever response in liquids, and to temperature variations. This technique has been applied for the detection of ethanol in aqueous solution by using the microbalance method, and for antibody/antigen recognition by the surface stress method. The results show the feasibility and very high sensitivity of these novel devices. PMID- 11215622 TI - Implementation of self-sensing SPM cantilevers for nano-force measurement in microrobotics. AB - Micromanipulation tasks have to be solved in the assembly of microsystems, the handling of biological cells and the handling of specimens for scanning electron microscopy. For these applications, we have developed a flexible micromanipulation station, including direct-driven robots a few cubic centimeters small. The robots are able to perform high-precise manipulation and positioning of microobjects. Force-controlled microgripping strategies are now necessary to develop robust microassembly strategies. Microgripping is different from conventional gripping in two ways. First, microparts with dimensions less than 100 microm are often fragile and can easily be damaged during gripping, thus special grasping techniques are needed. Second, the mechanics of manipulation in the microworld are much different than in the macro-world. Part interactions in the microworld are dominated by adhesive forces making it difficult to release parts during manipulation tasks. Several microgrippers that do not employ force feedback have been developed; force-controlled microgrippers are much less common. Grippers with integrated piezoresistive force sensors and with attached strain gauges have been reported. These approaches, however, are limited in their ability to resolve the gripping force. Hence, we are currently integrating self sensing SPM cantilevers into a gripper of our microrobots. These cantilevers operate by measuring stress-induced electrical resistance changes in an implanted conductive channel in the flexure legs of the cantilever. The real-time force feedback provided by these sensors enables us to better understand the prevailing nano forces and dynamics, what is indispensable for reliable micromanipulation strategies. PMID- 11215623 TI - Fabrication of quantum well microcantilever photon detectors. AB - We have developed a new method for fabricating quantum well microcantilever arrays that can be used in a variety of sensing applications. Microcantilevers with quantum wells allow real-time manipulation of energy states using external stress thus providing photon wavelength tunability. For example, this can result in an effective and rapid change in electron energy levels in photon detection devices. We applied this microfabrication technique to develop InSb microcantilevers and small arrays of GaAs/GaA1As microcantilever quantum wells. Such arrays can be useful in the detection of infrared (IR) radiation at room temperature. PMID- 11215624 TI - Thermomechanical noise of a free v-shaped cantilever for atomic-force microscopy. AB - We have calculated the thermal noise of a v-shaped AFM cantilever (Microlever, Type E, Thermomicroscopes) by means of a finite element analysis. The modal shapes of the first 10 eigenmodes are displayed as well as the numerical constants, which are needed for the calibration using the thermal noise method. In the first eigenmode, values for the thermomechanical noise of the z displacement at 22 degrees C temperature of square root of u2(1) = A/square root of c(cant) and the photodiode signal (normal-force) of S2(1) = A/square root of c(cant) were obtained. The results also indicate a systematic deviation ofthe spectral density of the thermomechanical noise of v-shaped cantilevers as compared to rectangular beam-shaped cantilevers. PMID- 11215625 TI - Intermittent contact AFM using the higher modes of weak cantilever. AB - Employing the higher vibration modes of weak cantilevers enables operating frequencies up to megahertz to be reached, at the same time keeping the force on the sample reasonably low. This allows the interaction time between the tip and the surface to be reduced and should cause the response of surface to be dominated by surface stiffness. The simple distributed mass cantilever model is presented which shows that higher eigenmodes exhibit better sensitivity to surface properties. The images of laser-treated polymer on glass show the ability of the method to distinguish between the material phases with different properties. PMID- 11215626 TI - Modeling of cylindrically tapered cantilevers for transverse dynamic force microscopy (TDFM). AB - In transverse dynamic force microscopy a cylindrically tapered cantilever is mounted perpendicularly to the sample surface and set into transversal oscillation. The dynamics of the cantilever has been studied using the continuum mechanical model with discrete element analysis. A viscoelastic model has been used to describe the tip-sample interaction. In this way an in-phase and an out of-phase component of the force has been extracted from the experimental data. Two different techniques, involving two experimental setups and two corresponding data analysis routines, have been developed to calculate the two components of the force at different tip-sample separations. In one case the change in resonant frequency and corresponding oscillation amplitude is measured whereas in the second case the usual way of recording amplitude and phase signal at a fixed driving frequency is applied. The results from these two methods are shown to be completely consistent and produce almost identical force curves. PMID- 11215627 TI - STM studies of 1-D noble metal growth on silicon. AB - Our scanning tunneling microscopy (STM) studies show that noble metals (Ag, Au) form a wide variety of 1-D structures on the high-index Si(5 5 12) surface. At coverages below 0.25 monolayer (ML), both metals grow as overlayer rows with an inter-row spacing of approximately 5 nm. At higher coverages and annealing temperatures, the underlying Si reconstruction is removed, but periodic row structures persist. Au can also induce faceting to nearby planes, e.g. (7 7 15) and (2 2 5), at temperatures above 500 degrees C. For all coverages and annealing temperatures studied here (0.02-1 ML, 450-800 degrees C), the Si(5 5 12) template initiates 1-D growth of the deposited noble metals. PMID- 11215628 TI - Imaging tip formation in single-mode optical fibres. AB - The formation of probe tips is a crucial step in all forms of scanning probe microscopy (SPM). In this work single-mode optical fibres are chemically etched in a variable temperature bath of etchant solution (HF acid buffered with ammonium fluoride) to produce tips for optical SPM. Tip evolution is monitored by prematurely truncating the etching process and imaging the tip end-structure using atomic force microscopy (AFM). In the case of a visible regime single-mode fibre the AFM images show a remarkable ring structure in the central cladding region and a tip structure in the core with a central depression; this serves to demonstrate the efficacy of chemical etching for converting compositional variation to three-dimensional topography. In the case of a standard, single-mode optical communications fibre the (projected) tip cone angle is assessed from AFM images in the early stages of tip formation. Values of the cone angle thus determined, for different etch conditions, are compared to those predicted by a model in which the independently determined core and cladding etch rates, and core diameter are the sole determinants of the final tip geometry. The model was devised in the context of etching multi-mode fibres and is shown to be valid here for single-mode fibres within the range of experimental accuracy and etch conditions examined. PMID- 11215629 TI - Scaling-index method as an image processing tool in scanning-probe microscopy. AB - The scaling-index method (SIM) is a novel tool for image processing in scanning probe microscopy. Originating from the theory of complex systems, the SIM can be used in order to extract structural information from arbitrary data sets. This method can readily be applied to the analysis of digital atomic-force microscopy (AFM) images. Especially for biomedical diagnostics, where genetic material is investigated by various microscopic methods, a reliable image segmentation based on the SIM algorithm is helpful. As a first application, AFM-images of GTG-banded human metaphase chromosomes (with G bands obtained by Trypsin using Giemsa) are compared with micrographs from conventional light microscopy by means of a scaling-index analysis. While the grey-level distributions of the optical and the AFM-images are largely different from each other, the scaling-index images are remarkably similar. Using this method, a fingerprint of an image can be produced which helps in the classification and interpretation of the measured data. PMID- 11215630 TI - A sample scanning system with nanometric accuracy for quantitative SPM measurements. AB - A sample scanning device operating in a working volume of 30 x 30 x 18 microm with interferometer and capacitance-based controls of displacements, is described. The xy-stage uses plane mirror linear interferometers and fast phase meters for control of displacements of precise ball-bearing stages driven by piezo flexure actuators. The stage operates with a full range bandwidth of 200 Hz, and an estimated accuracy (k = 2) of 3 nm + 1 x 10(-3) L, where L is the lateral displacement. A novel z-stage based on a kinematic coupling between two plates, the upper one being moved by three bimorph plates and the distance being measured by three capacitive sensor, is described. The tilt of the z-stage is kept within fractions of a microrad, leading to a full range estimated accuracy of 2 nm + 2 x 10(-3) h, where h is the vertical displacement. The control bandwidth is of about 1 kHz, thus allowing fast and accurate step-height measurements. In order to test the device used in a scanning probe microscope, micrometric patterned surfaces made using high resolution e-beam lithography and precise metal deposition on silicon are imaged. Results of pitch measurements are discussed and compared with those obtained using optical diffractometry. PMID- 11215631 TI - A model for the hillock formation on graphite surfaces by 246 MeV Kr+ ions. AB - Scanning tunnelling microscopy has been used to study the effect of ion bombardment at different angles of incidence on a graphite surface. The 246 MeV energy of Kr+ ions was selected in the medium energy range, where the electronic and nuclear stopping is nearly balanced. The low dose (1 x 10(12)/cm2) of ions allows the characterization of single features caused by bombardment in perpendicular, at 30 degrees and at 60 degrees incidence. The density of hillocks caused by the ion bombardment is significantly lower than the ion dose and this density depends on the angle of incidence. The hillocks are attributed to knocked on atoms leaving the sample surface. A simple model for the scattering process is presented to enlighten the hillock density differences. Other features produced by the ion bombardment, such as elongated traces and (square root of 3 x square root of 3) R30 superstructures are also reported. PMID- 11215632 TI - Role of ripening and defects in the formation of mesotaxial cobalt-disilicide layers. AB - Previous studies of the formation of buried silicide layers through mesotaxy, i.e., the introduction of the metal component by ion implantation with subsequent annealing of the structure, have shown that high-quality films can be achieved, but at processing temperatures too high to be useful for integration with silicon device technology. Recently, we proposed a modified ripening model to describe the early stages of the formation of a buried film which intentionally excluded the role of defects. In the current study, the predictions of that model are tested by varying sample preparation conditions. We show that the shift of the silicide precipitate layer is correlated with the narrowing of the cobalt profile, thus requiring both processes to be described by the same mechanism. We also show in a TEM study that specific defect morphologies are correlated with specific properties of the forming buried film, requiring an extension of the previous model. PMID- 11215633 TI - Nanotribology of Si oxide layers on Si by atomic force microscopy. AB - Atomic force microscopy (AFM) has been used for tribological studies of Si surfaces covered by oxide layers of various kinds: chemical oxides prepared by the SC1 (NH4OH/H2O2/H2O) and the SC2 (HCl/H2O2/H2O) treatments and a thermal oxide. In the case of the SC1 chemical oxide, the oxide layer was scratched and the underlying Si substrate was ploughed by the Si3N4 AFM tip. On the other hand, no wear of the sample was noted on the other surfaces: the AFM often produced elevated patterns in the shape of the scanned area, which were no longer visible after HF etching. By annealing the SC1-treated surface in N2 gas at above 200 degrees C for 30 min, the oxide layer could not be scratched any more. By soaking the thermal oxide in KOH, the oxide layer was then scratched. It is concluded that the presence of OH bases is the necessary condition for the nano-scratching of the oxide layers. PMID- 11215634 TI - Atomic surface characterisation and modification of the layered compounds Bi2Se3, Bi1.9Sb0.1Se3 and Bi1.6Sb0.4Se3. AB - In this work, we show atomic STM images of the layered compound Bi2Se3. We study the effect in the surface of the substitution of 5% and 20% of the Bi atoms for Sb in Bi1.9Sb0.1Se3 and Bi1.6Sb0.4Se3. The images of the three samples show similar trigonal structures corresponding probably to the van der Waals Se atoms. The distance measured between surface atoms in Bi2Se3 is 4.04 A, in Bi1.9Sb0.1Se3 is 4.16 A and in Bi1.6Sb0.4Se3 is 4.26 A. In Bi1.6Sb0.4Se3 some atomic sites appear brighter than others. The effect is accentuated at higher tunnelling currents and is not observed in the other compounds. Nanoscopic range depressions on the sample might be related to the skeletal crystal structure since the images show atomic corrugations that align slightly in one direction. We explain the results as the effects of the interactions between tip and sample, and discuss two interpretations: on the one hand, localised depression of the individual atomic sites, and on the other the possible elevation of the atoms of the surface due to a phase transition of the compounds induced by STM. PMID- 11215635 TI - Chemical force microscopy of self-assembled monolayers on sputtered gold films patterned by phase separation. AB - Patterned self-assembled monolayers (SAMs) were formed on gold films and observed by friction force microscopy (FFM) and adhesive force mapping with pulsed-force mode atomic force microscopy (PFM-AFM). The substrate gold films were prepared by sputtering gold on flat surfaces of osmium-coated cover glass with surface roughness, Ra, of 0.3 nm. The patterned samples with the CH3 and COOH terminated regions were prepared using the Langmuir-Blodgett (LB) method, partial removal of the LB film by ultrasonication, and SAM formation. The CH3 and COOH terminated regions of the patterned SAMs in air and in water were observed by mapping friction and adhesive forces with FFM and PFM-AFM, respectively, using gold coated AFM tips chemically modified with a thiol compound terminating in CH3 or COOH. The adhesive forces measured in air increased in the order of CH3/CH3, CH3/COOH (or COOH/CH3) and COOH/COOH, while those in water increased in reverse order. The enormous high adhesive force observed in water for CH3/CH3 was attributed to hydrophobic interaction between the CH3 tip and the CH3 terminated sample surface. With CH3 tip, the lower friction force was observed, however, in water on the CH3 terminated region than on the COOH terminated region. This experimental finding raises a question as to what is the effective normal load in friction measurements in water. PMID- 11215636 TI - Study of microcontact printed patterns by chemical force microscopy. AB - Patterned self-assembled monolayers (SAMs) on sputtered gold films prepared by microcontact printing (microCP) were studied by mapping adhesive forces with pulsed-force-mode atomic force microscopy. A stamp for microCP was fabricated by pouring polydimethylsiloxane (PDMS) over a photolithographically prepared master. The patterned SAMs were prepared by two methods. One is called the wet-inking method, in which inking was done by placing a thiol ethanol solution for 30 s on the stamp and then removing the excess ink solution under a stream of nitrogen. The other is called the contact-inking method, in which a pad made of PDMS was dipped overnight in a thiol ethanol solution and then the stamp was placed on the inker pad impregnated with the thiol ethanol solution. The second step for pattern formation was the same for both of the two different microCP methods. Namely, the gold surfaces stamped with alkanethiols were further reacted with a thiol terminating in COOH in ethanol. The resulting patterns with CH3- and COOH terminated regions were analyzed by imaging the adhesive forces with the chemically modified gold coated AFM tips with a SAM of CH3 or COOH terminal functional groups. PMID- 11215638 TI - EGF-stimulated lamellipod extension in adenocarcinoma cells. AB - The extension of lamellipodia has been triggered by the application of epidermal growth factor (EGF). We have used an atomic force microscope (AFM) to investigate this lamellipodial extension. During extension we could detect an increase in height from about 500 nm for the stable lamellipodium to typical values of 600 800 nm for the extending lamellipodium. The AFM was also used to determine the mechanical properties of the lamellipodium where we found a decrease of the elastic modulus by a factor of 1.4 at the same location within the same cell. Both findings are consistent with the cortical expansion hypothesis, suggesting that severing of actin filaments, leading to a swelling of the cytoskeleton, generates the protrusive force during lamellipodial extension. PMID- 11215637 TI - Atomic force microscopy can be used to mechanically stimulate osteoblasts and evaluate cellular strain distributions. AB - In this study, atomic force microscopy (AFM) was used to mechanically stimulate primary osteoblasts. In response to mechanical force applied by the AFM, the indented cell increased its intracellular calcium concentration. The material properties of the cell could be estimated and the membrane strains calculated. We proceeded to validate this technique experimentally and a 20% error was found between the predicted and the measured diameter of indentation. We also determined the strain distributions within the cell that result from AFM indentation using a simple finite element model. This enabled us to formulate hypotheses as to the mechanism through which cells may sense the applied mechanical strains. Finally, we report the effect of the Poisson ratio and the cell thickness on the strain distributions. Varying the Poisson ratio did not change the order of magnitude of the strains; whereas the cellular thickness dramatically changed the order of magnitude of the cellular strains. We conclude that AFM can be used for controlled mechanical stimulation of osteoblasts and that cellular strain distributions can be computed with a good accuracy when the cell is indented in its highest part. PMID- 11215639 TI - Bioremediation of residual fertilizer nitrate: I. Laboratory demonstration of an on-farm in situ pollution control system. AB - This exploratory laboratory study was undertaken to develop and test an in situ bioremediation system intended to point the way toward a possible field application. The proposed method uses a water table management (WTM) system to deliver nutrients or other amendments to subsoil microorganisms for biostimulation and subsequent biodegradation of pollutants in the saturated and unsaturated zones of the soil. The study was carried out on packed soil columns and bioremediation of residual fertilizer nitrate was attempted. Different levels of organic carbon supplement (glucose C) were introduced into these columns via subirrigation in order to supplement the readily available organic carbon levels in the soil. The study was carried out in two experimental setups. The first setup investigated (i) the effect of addition of a high (970 mg L(-1)) and a low (120 mg L(-1)) glucose C level and (ii) the efficacy of using the subirrigation system as a method for nutrient delivery in bioremediation of leached nitrate. This setup was monitored with time, depth, and with reference to the nitrate residue in the soil solution. Leached nitrate was denitrified to less than 10 mg L(-1) nitrate N at both glucose levels. The second setup investigated the effect of a range of low levels of glucose C on nitrate decontamination, soil pH, and total microbial count in order to find out an optimal glucose C level that reduced the most nitrate and maintained the pH homeostasis of soil. PMID- 11215640 TI - Spatial extrapolation of soil characteristics using whole-soil particle size distributions. AB - Soils support ecosystem functions such as plant growth and water quality because of certain physical, chemical, and biological properties. These properties have been studied at different spatial scales, including point scales to satisfy basic research needs, and regional scales to satisfy monitoring needs. Recently, soil property data for the entire USA have become available in the State Soil Geographic Data Base (STATSGO), which is appropriate for regional-scale research. We analyzed and created models of STATSGO data in this study to serve as a research tool, for example, for linking the soil to regional water quality monitoring data in our companion paper. Map units in STATSGO define geographic land areas by soil characteristics (SCs) of similar soil series. We selected 27 SCs that influenced water properties (in varying degrees), aggregated the layer and component SCs to map unit SCs, and used SCs to calculate relationships among map units. The relationships were defined by equations of conditional mean for the qth SC (SCq), while using the remaining 26 SCs as predictors. The relative standard errors for 22 of the 27 SCs were less than 10%, and less than 22% for the remaining five. We conclude that spatial extrapolation of SCs is feasible and the procedures are a first step toward extrapolating information across a region using SC-water property relationships. Although our procedure is for regional scale monitoring, it is also applicable to finer spatial scales commensurate with available soil data. PMID- 11215641 TI - Bioremediation of residual fertilizer nitrate: II. Soil redox potential and soluble iron as indicators of soil health during treatment. AB - The prospect of using wastewater containing high loads of soluble organic matter (OM) for removing residual agricultural chemicals (fertilizer, pesticide, or herbicide) in farm soil, although promising, could have adverse effects on soil agricultural quality as a result of development of redoximorphic features in the soil profile. In this study, the effect of organic carbon supplement for bioremediation of residual fertilizer nitrate on soil properties, redox potential (Eh), pH, and metal ion mobilization was studied using sandy soils packed in columns. The study was included in a general project, described elsewhere (Ugwuegbu et al., 2000), undertaken to evaluate use of controlled water table management (WTM) systems to supply organic carbon for creating a reduced environment conducive to denitrification of residual fertilizer nitrate leaching from the farm to subsurface water. The columns were subjected to subirrigation with water containing soluble organic carbon in the form of glucose. The work was carried out in two experimental setups and the long-term effect of a range of glucose concentrations on the Eh, pH, and soluble levels of Fe and Mn was investigated. From the results obtained, it could be concluded that excessive organic carbon supplement to soil can have adverse effects on soil quality and that Eh and soluble Fe are the two most practical parameters for monitoring soil health during treatment of farm chemicals. PMID- 11215642 TI - Predicting physical and chemical water properties from relationships with watershed soil characteristics. AB - The Surface Waters component of the Environmental Monitoring and Assessment Program (EMAPSW) was developed by the USEPA to evaluate the extent and condition of lakes and streams over national and regional scales. Realistically, chemical or physical water properties (WPs) such as acidity or turbidity can be field sampled for only a small portion of all lakes and streams. However, soil characteristics (SCs) affect WPs and broad-scale soil survey data have become available in the State Soil Geographic Data Base (STATSGO). We developed models relating observed WPs to SCs to extrapolate the sampled WPs to a region, potentially reducing extensive monitoring needs. Our study region consisted of 13 northeastern and Mid-Atlantic states and contained 882 STATSGO soil map units. We used map units as the spatial component of WP analysis. The WPs were sampled in 721 randomly selected EMAPSW study sites. The watersheds of these sites represent 7.1% of the region's total area and spatially intersect 400 of its soil map units. Each intersected map unit was assigned the weighted average WPs from the corresponding watersheds. Conditional expectation models were used to extrapolate sampled WPs to 882 map units. The relative standard errors ranged from low for pH (0.8%), intermediate for total P (12.1%), and very high for chloride (54.8%). The high extrapolation errors indicate outlier conditions from natural, non-soil, or anthropogenic sources. PMID- 11215643 TI - Photodegradation of selected herbicides in various natural waters and soils under environmental conditions. AB - The photochemical degradation of herbicides belonging to different chemical groups has been investigated in different types of natural waters (ground, river, lake, marine) and distilled water as well as in soils with different texture and composition. Studied herbicides and chemical groups included atrazine, propazine, and prometryne (s-triazines); propachlor and propanil (acetanilides); and molinate (thiocarbamate). The degradation kinetics were monitored under natural conditions of sunlight and temperature. Photodegradation experiments were performed in May through July 1998 at low concentrations in water samples (2-10 mg/L) and soil samples (5-20 mg/kg), which are close to usual field dosage. The photodegradation rates of all studied herbicides in different natural waters followed a pseudo-first order kinetics. The half-lives of the selected herbicides varied from 26 to 73 calendar days in waters and from 12 to 40 d in soil surfaces, showing that the degradation process depends on the constitution of the irradiated media. The presence of humic substances in the lake, river, and marine water samples reduces degradation rates in comparison with the distilled and ground water. On the contrary, the degradation in soil is accelerated as the percentage of organic matter increases. Generally, the photodegradation process in soil is faster than in water. The major photodegradation products identified by using gas chromatography-mass spectrometry (GC-MS) techniques were the hydroxy and dealkylated derivatives for s-triazines, the dechlorinated and hydroxy derivative for the anilides, and the keto-derivative for the thiocarbamate, indicating a similar mode of degradation for each chemical category. PMID- 11215644 TI - Behavior of cinosulfuron in paddy surface waters, sediments, and ground water. AB - Cinosulfuron (3-(4,6-dimethoxy-1,3,5-triazin-2-yl)-1-[2-(2-methoxyethoxy) phenylsulfonyl]-urea) is a sulfonylurea herbicide used to control a wide range of broadleaf weeds in rice (Oryza sativa L.). A 2-yr field study was conducted in northwest Italy to determine the effect of cinosulfuron on surface and subsoil waters in rice paddies. Cinosulfuron was applied at 70 g a.i. ha(-1) on 35 ha of flooded rice. After the treatment, the change in herbicide concentration over time was studied by analyzing water and sediment samples in a test paddy field (2.16 ha, located in the treated area), water in a spring and a pond (both located near the test paddy), two wells (up- and downhill to the treated area), and two piezometers (along the test paddy levee). To better understand some of the field study results, cinosulfuron degradation was also evaluated in the laboratory in solutions buffered to different pH values. Two weeks after the treatment, the cinosulfuron concentration in the paddy water decreased by about 60%. No cinosulfuron was detected at about 2.5 mo after the treatment. The concentration in the sediment gradually increased after the treatment, reaching the highest value (13.53 microg kg(-1)) 3 wk later. The maximum cinosulfuron content in the spring and pond were 0.91 and 0.29 microg L(-1), respectively, and these were detected 60 to 90 days after treatment (DAT). The water collected in the piezometers reached the highest concentration (0.99 microg L(-1)) 29 DAT. Cinosulfuron was never detected in the wells. In the degradation study at different pH values, cinosulfuron degraded rapidly at low pH values. PMID- 11215645 TI - Bioavailability of biosolids molybdenum to corn. AB - This study was part of a larger effort to generate field data appropriate to the assessment of biosolids molybdenum (Mo) risk to ruminants. Corn (Zea mays L.) is an important component of cattle diet, and is a logical crop for biosolids amendment owing to its high N requirement. Paired soil and corn stover samples archived from two unique field experiments were analyzed to quantify the relationship (uptake coefficient, UC) between stover Mo and soil Mo load. Both studies used biosolids with total Mo concentrations typical of modern materials. Data from long-term (continuous corn) plots in Fulton County, IL confirm expected low Mo accumulation by corn stover, even at very high biosolids loads and soil Mo loads estimated to be near 18 kg Mo ha(-1). Uptake slopes were actually negative, but USEPA protocol would assign UC values of 0.001. Data from plots in Minnesota also suggested essentially no correlations between stover Mo and soil Mo loads for continuous corn. However, greater Mo accumulation in corn grown following soybean [Glycine max (L.) Merr.] suggests the possibility of enhanced Mo bioavailability to corn in corn-soybean rotations. Nevertheless, molybdenosis risk to cattle consuming corn stover produced on biosolids-amended land is small as stover Mo concentrations were always low and stover Cu to Mo ratios exceeded 2:1, which avoids molybdenosis problems. PMID- 11215646 TI - The relationship between microbial carbon and the resource quality of soil carbon. AB - The biological health of soil is an important aspect of soil quality because of the many critical functions performed by organisms in soil. Various indicators of soil quality have been proposed, but measurements of microbial biomass are most commonly used. During decomposition of plant residues in soil the relative intensities of the O-alkyl-C signal decreases and the alkyl-C signal increases in nuclear magnetic resonance (NMR) spectra. This leads to the suggestion that the alkyl-C to O-alkyl-C ratio of a soil may indicate the degree of decomposition. Consequently, the overall resource quality of soil C as a substrate for heterotrophic microorganisms may be inversely related to the alkyl-C to O-alkyl-C ratio. Our hypothesis is that a relationship exists between the size of the soil microbial community (microbial biomass) and the quality of soil carbon as a resource for microorganisms. New data have been combined with previously published data to show that there was a significant, negative correlation between the biomass C to total C (Cmic, to Corg) ratio and the alkyl-C to O-alkyl-C ratio (p < 0.01), which supports our hypothesis. PMID- 11215647 TI - Modeling pollutant release from a surface source during rainfall runoff. AB - Though runoff from manure spread fields is recognized as an important mode of nonpoint-source pollution, there are no models that mechanistically describe transport from a field-spread manure-type source. A mechanistic, physically based model for pollutant release from a surface source, such as field-spread manure, was hypothesized, laboratory tested, and field-applied. The primary objective of this study was to demonstrate the potential applicability of a mechanistic model to pollutant release from surface sources. The laboratory investigation used stable sources and a conservative "pollutant" (KCl) so that the dynamic effects of source dissolution and chemical transformations could be ignored and transport processes isolated. The field investigation used runoff and soluble reactive phosphorus (SP) data collected from a dairy-manure-spread field in the Cannonsville watershed in the Catskills region of New York State. The model predictions corroborated well with observations of runoff and pollutant delivery in both the laboratory and the field. "Pollutant" release from surface sources was generally predicted within 11% of laboratory KCl measurements and field SP observations. Laboratory flume runoff predictions with 15 and 26% errors for 25 and 15 mm h(-1) simulated rainfall intensity experiments, respectively, represented root mean square errors of less than 0.2 mLs(-1). A 26% error was calculated for overland flow predictions in the field, which translated into approximately a 39 mLs(-1) error. Results suggest that the hypothesized model satisfactorily represents the primary mechanisms in pollutant release from surface sources. PMID- 11215648 TI - Biosolids application in the Chihuahuan desert: effects on runoff water quality. AB - Surface-applied biosolids, the option most often used on range-lands, can increase the concentration of macronutrients and trace elements in the runoff water and can potentially produce eutrophication or contamination of surface waters. In this study, the effects of postapplication age of biosolids (18, 12, 6, and 0.5 mo) and rate of application (0, 7, 18, 34, and 90 Mg ha(-1)) on the quality of runoff water from shrubland and grassland soils were assessed. Between July and October 1996 simulated rainfall was applied to 0.50-m2 plots for 30 min at a rate of 160 mm h(-1). All of the runoff water was collected. The concentration of NH4+ -N, NO3- -N, PO4(3-)-P, total dissolved phosphorus (TDP), Cu, and Mn in the runoff water increased with rate of biosolids application and decreased with time of postapplication on the two soils. The highest PO4(3-)-P and NH4+ -N concentrations, 4.96 and 97 mg L(-1), respectively, were recorded in the grassland soil treated with 90 Mg ha(-1) of biosolids 0.5 mo postapplication. For the same soil, rate, and postapplication age of biosolids, Cu exceeded the upper limit (0.50 mg L(-1) in drinking water for livestock. Ammonium N and PO4(3 )-P should be the main compounds considered when surface-applying biosolids. Ammonium N at concentrations found in all biosolids-treated plots may affect the quality of livestock drinking water by causing taste and smell problems. Orthophosphate can contribute to eutrophication if the runoff from biosolids treated areas enter surface waters. PMID- 11215649 TI - Using zebra mussels to monitor Escherichia coli in environmental waters. AB - Use of the zebra mussel (Dreissena polymorpha) as an indicator of previously elevated bacteria concentrations in a watershed was examined. The ability of the zebra mussel to accumulate and purge Escherichia coli over several days was investigated in both laboratory and field experiments. In laboratory experiments, periodic enumeration of E. coli in mussels that had been exposed to a dilute solution of raw sewage demonstrated that (i) maximum concentrations of E. coli are reached within a few hours of exposure to sewage, (ii) the tissue concentration attained is higher than the concentration in the ambient water, and (iii) the E. coli concentrations take several days to return to preexposure concentrations when mussels are subsequently placed in sterile water. In field experiments conducted in southeast Michigan in the Clinton River watershed, brief increases in E. coli concentrations in the water were accompanied by increases in mussel concentrations of E. coli that lasted 2 or 3 d. The ability of mussels to retain and to concentrate E. coli made it possible to detect E. coli in the environment under conditions that conventional monitoring may often miss. Sampling caged mussels in a river and its tributaries may enable watershed managers to reduce the sampling frequency normally required to identify critical E. coli sources, thereby providing a more cost-effective river monitoring strategy for bacterial contamination. PMID- 11215650 TI - In vitro pesticide degradation in turfgrass soil incubated under open and sealed conditions. AB - Degradation of selected pesticides was conducted in a turfgrass soil from a golf course under open (i.e., allowing gas exchange with atmosphere) and sealed systems. The time required for 50% of the initial dose of fenitrothion (O,O dimethyl O-4-nitro-m-tolyl phosphorothioate), diazinon (O,O-dimethyl O-2 isopropyl-6-methylpyrimidin4-yl phosphorothioate), iprodione [3-(3,5 dichlorophenyl)-N-isopropyl-2,4-dioxo-imidazolidine-1-carboxamide], mecoprop [(RS)-2-(4-chloro-otolyloxy)propionic acid], and asulam (4-aminophenylsulfonyl carbamate) to dissipate (half-life, t 1/2) was less than 2 wk under both conditions. The t 1/2 values of dithiopyr (S,S'-dimethyl 2-difluoromethyl-4 isobutyl-6-trifluoro-methylpyridine-3,5-dicarbothioate) were 324 and 185 d under the open and sealed conditions, respectively. The t 1/2 values of isoprothiolane (di-isopropyl 1,3-dithiolan-2-ylidene-malonate), flutolanil (alpha,alpha,alpha trifluoro-3'-isopropoxy-o-toluanilide), and benefin (N-butyl-N-ethyl alpha,alpha,alpha-trifluoro-2,6-dinitro-p-toluidine) under the open conditions were 154, 336, and 47 d, respectively. The t 1/2 values of these pesticides increased slightly under the sealed conditions. The t 1/2 values of terbutol (2,6 di-tert-butyl-4-methylphenyl N-methycarbamate) and one of the major degradation products, N-demethyl-terbutol (2,6-di-tert-butyl-4-methylphenyl carbamate), were 182 and 291 d under the open conditions and increased by six- and threefold under the sealed conditions, respectively. The degradation system under the sealed conditions could characterize the persistence of terbutol and N-demethyl terbutol, which were the most persistent in the field. PMID- 11215651 TI - Phosphorus transfer in runoff following application of fertilizer, manure, and sewage sludge. AB - Phosphorus (P) transfer in surface runoff from field plots receiving either no P, triplesuperphoshate (TSP), liquid cattle manure (LCS), liquid anaerobically digested sludge (LDS), or dewatered sludge cake (DSC) was compared over a 2-yr period. Dissolved inorganic P concentrations in runoff increased from 0.1 to 0.2 mg L(-1) on control and sludge-treated plots to 3.8 and 6.5 mg L(-1) following application of LCS and TSP, respectively, to a cereal crop in spring. When incorporated into the soil in autumn, runoff dissolved P concentrations were typically < 0.5 mg L(-1) across all plots, and particulate P remained the dominant P form. When surface-applied in autumn to a consolidated seedbed, direct loss of LCS and LDS increased both runoff volume and P transfers, but release of dissolved P occurred only from LCS. The largest P concentrations (>70 mg L(-1)) were recorded following TSP application without any increase in runoff volume, while application of bulky DSC significantly reduced total P transfers by 70% compared with the control due to a reduced runoff volume. Treatment effects in each monitoring period were most pronounced in the first runoff event. Differences in the release of P from the different P sources were related to the amounts of P extracted by either water or sodium bicarbonate in the order TSP > LCS > LDS > DSC. The results suggest there is a lower risk of P transfer in land runoff following application of sludge compared with other agricultural P amendments at similar P rates. PMID- 11215652 TI - Nitrogen fertilization effects on stream water cadmium concentration. AB - High transition metal concentrations were previously unexpectedly observed in soil water extracted by suction lysimeters following forest N fertilization. This observation called for additional measurements to investigate if the finding is a general phenomenon and, if so, whether stream water concentrations of transition metals could increase as a result of N fertilization. The measured levels of Cd in the preliminary findings were well above health limits for drinking water. Hence, the problem could be of major concern. Here we report on soil water and stream water concentrations at two partly fertilized watersheds. All sites were situated in the central part of Sweden. The N application (150 kg N ha(-1) in the form of calcium ammonium nitrate) resulted in increased concentrations of nitrate, and a pulse of acidity through the soil profile, which increased the solubility of transition metals (mainly Cd and Zn) and Al. Stream water concentrations of transition metals, on the other hand, were not affected during the studied period by the increased solubility of transition metals in the soil. The data imply that the solubilized transition metals probably insolubilize further down the soil profile, and that there is no risk from forest N fertilization (at normal soil pH levels) of transition metal levels increasing in nearby surface waters. To our knowledge, this is the first time this side effect of N fertilization has been considered. PMID- 11215653 TI - Field-scale preferential transport of water and chloride tracer by depression focused recharge. AB - A tracer study was initiated in November 1993 to investigate depression-focused recharge and to monitor solute movement through the vadose zone into the shallow ground water in southeastern North Dakota. Granular potassium chloride (KCl) was surface-applied to two areas overlying subsurface drains and to one area instrumented with soil solution samplers, ground water monitoring wells, time domain reflectometry (TDR) probes, and temperature probes. One of the subsurface drain tracer plots was located on level ground while the other two sites were in small topographic depressions. Formation of ground water mounds beneath the depressions indicated that these areas are recharge sites. The applied Cl- tracer was found to move rapidly to the shallow ground water under the depressional areas after infiltration of spring snowmelt in 1994. Excessive rainfall events were also responsible for focused recharge and the rapid transport of the applied Cl- tracer. Water flow through partially frozen soil at the bottom of the depressions during thaw enhanced preferential movement of the tracer. PMID- 11215654 TI - Artificial recharge of humic ground water. AB - The purpose of this study was to investigate the efficiency of soil in removing natural organic matter from humic ground waters using artificial recharge. The study site, in western Denmark, was a 10,000 ml football field of which 2,000 m2 served as an infiltration field. The impact of the artificial recharge was studied by monitoring the water level and the quality of the underlying shallow aquifer. The humic ground water contained mainly humic adds with an organic carbon (OC) concentration of 100 to 200 mg C L(-1). A total of 5,000 mS of humic ground water were sprinkled onto the infiltration field at an average rate of 4.25 mm h(-1). This resulted in a rise in the water table of the shallow aquifer. The organic matter concentration of the water in the shallow aquifer, however, remained below 2.7 mg C L(-1). The organic matter concentration of the pore water in the unsaturated zone was measured at the end of the experiment. The organic matter concentration of the pore water decreased from 105 mg C L(-1) at 0.5 m to 20 mg C L(-1) at 2.5 m under the infiltration field indicating that the soil removed the organic matter from the humic ground water. From these results we conclude that artificial recharge is a possible method for humic ground water treatment. PMID- 11215655 TI - Nutrient movement and removal in a switchgrass biomass-filter strip system treated with dairy manure. AB - Manure use on cropland has raised concern about nutrient contamination of surface and ground waters. Warm-season perennial grasses may be useful in filter strips to trap manure nutrients and as biomass feedstock for nutrient removal. We explored the use of 'Alamo' switchgrass (Panicum virgatum L.) in a biomass production-filter strip system treated with dairy manure. We measured changes in extractable P in the soil, NO3 -N in soil water, and changes in total reactive P and chemical oxygen demand (COD) of runoff water before and after a switchgrass filter strip. Five rates of dairy manure (target rates of 0, 50, 100, 150, and 200 kg N ha(-1) from solid manure in 1995; 0, 75, 150, 300, and 600 kg N ha(-1) from lagoon effluent in 1996 and 1997) were surface-applied to field plots of switchgrass (5.2 by 16.4 m) with a 5.2- by 16.4-m switchgrass filter strip below the manured area. Yield of switchgrass from the manured area increased linearly with increasing manure rate in each year. Soil water samples collected at 46 or 91 cm below the soil surface on 30 dates indicated < 3 mg L(-1) of NO3-N in all plots. Concentrations of total reactive P in surface runoff water were reduced an average of 47% for the 150 kg N rate and 76% for the 600 kg N rate in 1996 and 1997 after passing through the strip. Manure could effectively substitute for inorganic fertilizer in switchgrass biomass production with dual use of the switchgrass as a vegetative filter strip. PMID- 11215656 TI - Rapid methods to determine potentially mineralizable nitrogen in broiler litter. AB - Although broiler (chicken, Gallus gallus domesticus) litter has long been used as a fertilizer, estimating the rate required to supply a desired amount of plant available N is still hampered by the lack of rapid methods to estimate potentially mineralizable nitrogen (PMN). Previous research has suggested that near infrared reflectance spectroscopy (NIRS) and certain poultry litter characteristics, such as water-soluble organic nitrogen (WSON), may be useful for estimating PMN. The objectives of this study were to evaluate NIRS and WSON as tools to estimate PMN in broiler litter. Sixty sieved (2 mm) and freeze-dried broiler litter samples were mixed with Cowarts sandy loam soil (fine-loamy, kaolinitic, thermic Typic Kanhapludult) and incubated at 25 degrees C for 112 d. Cumulative net N mineralized with time was fitted to a single-pool exponential model to determine PMN for each broiler litter sample. The PMN values obtained were regressed against NIRS (780 to 2500 nm) and WSON measurements. We found strong relationships between measured- and NIRS-predicted PMN (R2 = 0.82), and between measured PMN and WSON (R2 = 0.87). These results demonstrate the feasibility of using either of these two methods to estimate PMN in broiler litter. Future work should further test both methods for their ability to estimate mineralizable N in whole, moist broiler litter under field conditions. PMID- 11215657 TI - Effects of sample storage on biosolids compost stability and maturity evaluation. AB - Compost stability and maturity are important parameters of compost quality. To date, nearly all compost characterization has been performed using samples freshly collected because sample storage can affect compost stability and maturity evaluation. However, sample preservation is sometimes necessary, especially for scientific research purposes. There is little information available on the effects of sample storage on compost stability and maturity. Samples of biosolids compost with different levels of stability and maturity were collected from four compost facilities in Florida (referred to as Register, Winslow, Sunset, and Meadow). Comparisons of CO2 evolution, seed germination rate, and water-soluble organic carbon (WSOC) were made between fresh samples with short storage at 4 degrees C for less than 1 wk and air-dried or frozen compost samples stored for 1 yr. The effects of storage (air-dry or frozen) on the measured parameters depended on compost stability and maturity and on the compost material source. Frozen storage reduced the peak CO2 evolution of Register samples by 12 to 29%, while accumulated CO2 evolution was reduced by 43 to 64% and 110 to 277% with air-dry and frozen storage, respectively. The storage effect on CO2 evolution with more stable compost was inconsistent. Storage did not affect compost phytotoxicity, except for samples from the Sunset facility. Air-drying reduced the WSOC by up to 35%, and freezing increased it by up to 34%, while both storage methods had no significant effect on samples of low WSOC. Despite all these variations, WSOC had a significant and consistent relation to CO2 evolution and seed germination rates with R2 of 0.78 and 0.57, respectively, regardless of storage methods. PMID- 11215658 TI - Phosphorus accumulation in cultivated soils from long-term annual applications of cattle feedlot manure. AB - Historically, manure has been recognized as an excellent soil amendment that can improve soil quality and provide nutrients for crop production. In areas of high animal density, however, the potential for water pollution resulting from improper storage or disposal of manure may be significant. The objective of this study was to determine the P balance of cultivated soils under barley (Hordeum vulgare L.) production that have received long-term annual manure amendments. Nonirrigated soils at the study site in Lethbridge, AB, Canada, have received 0, 30, 60, or 90 Mg manure ha(-1) (wet wt. basis) while irrigated plots received 0, 60, 120, and 180 Mg ha(-1) annually for 16 yr. The amount of P removed in barley grain and straw during the 16-yr period was between 5 and 18% of the cumulative manure P applied. There was a balance between P applied in manure and P recovered in crops and soils (to the 150-cm depth) of nonirrigated plots during the 16-yr study. In irrigated plots, as much as 1.4 Mg P ha(-1) added (180 Mg ha(-1) yr(-1) treatment) was not recovered over 16 yr, and was probably lost through leaching. The risk of ground water contamination with P from manure was greater in irrigated than nonirrigated plots that have received long-term annual manure amendments. Manure application rates should be reduced in nonirrigated and irrigated plots to more closely match manure P inputs to crop P requirements. PMID- 11215659 TI - Transport of Escherichia coli in sand columns with constant and changing water contents. AB - Understanding how changes in volumetric water content (theta) affect bacterial adsorption could help reduce transport of pathogenic and indicator bacteria that may be present in infiltrating wastewater. Three flow regimes that simulated infiltration from a household septic system were evaluated: saturated, unsaturated with a constant volumetric water content theta (constant unsaturated flow), and unsaturated with cyclic changes in theta (variable unsaturated flow). Escherichia coli was suspended in artificial sewage (AS) and applied as step inputs to sand columns, with regular interruptions in input for variable unsaturated flow. A transport model was fit to the saturated and constant unsaturated flow breakthrough curves to determine retardation (R), the first order filtration coefficient (mu), and the maximum outflow relative concentration (Cmax). The total cells transported as a fraction of input (tau) in all three flow regimes was calculated. Constant unsaturated flow resulted in a significantly lower Cmax (0.633) in comparison with saturated flow (0.803, P < or = 0.05), although unsaturated mu (0.0693 h(-1)) was not significantly different from saturated mu (0.0259 h(-1)). Constant unsaturated flow also resulted in a significantly smaller tau (0.617) than saturated (0.806) or variable unsaturated flow (0.734). In variable unsaturated flow, cell concentrations were out of phase with theta--as the column drained, cell concentrations in the outflow increased; and when a pulse of suspension was applied, cell concentrations decreased. Constant unsaturated flow is probably the best for removal of pathogenic bacteria because this regime resulted in lower maximum concentrations of E. coli and greater cell removal, in comparison with saturated and variable unsaturated flow. PMID- 11215660 TI - Potential mineralization of four herbicides in a ground water--fed wetland area. AB - Herbicides may leach from agricultural fields into ground water feeding adjacent wetlands. However, only little is known of the fate of herbicides in wetland areas. The purpose of the study was to examine the potential of a riparian fen to mineralize herbides that could leach from an adjacent catchment area. Slurries were prepared from sediment and ground water collected from different parts of a wetland representing different redox conditions. The slurries were amended with O2, NO3-, SO4(2-), and CO2, or CO2 alone as electron acceptors to simulate the in situ conditions and their ability to mineralize the herbides mecoprop, metsulfuron-methyl, isoproturon and atrazine. In addition, the abundance of bacteria able to utilize O2, NO3-, SO4(2-) + CO2, and CO2 as electron acceptors was investigated along with the O2-reducing and methanogenic potential of the sediment. The recalcitrance to bacterial degradation depended on both the type of herbicide and the redox conditions pertaining. Mecoprop was the most readily degraded herbicide, with 36% of [ring-U-14C]mecoprop being mineralized to 14CO2 under aerobic conditions after 473 d. In comparison, approximately 29% of [phenyl U-14C]metsulfuron-methyl and 16% of [ring-U-14C]isoproturon mineralized in aerobic slurries during the same period. Surprisingly, 8 to 13% of mecoprop also mineralized under anaerobic conditions. Neither metsulfuron-methyl nor isoproturon were mineralized under anaerobic conditions and atrazine was not mineralized under any of the redox conditions examined. The present study is the first to report mineralization of meco-prop in ground water in a wetland area, and the first to report mineralization of a phenoxyalcanoic acid herbicide under both aerobic and anaerobic conditions. PMID- 11215661 TI - Chemical characterization of synthetic soil from composting coal combustion and pharmaceutical by-products. AB - Land application of coal combustion by-products (CCBs) mixed with solid organic wastes (SOWs), such as municipal sewage sludge, has become increasingly popular as a means of productively using what were once considered waste products. Although bulk chemical and physical properties of several of these CCB-SOW materials have been reported, detailed information about their synthesis and mineralogy of the CCB-SOW materials has not been reported. In this paper, chemical and mineralogical properties of a soil-like material obtained from composting a mixture of CCBs with a pharmaceutical fermentation by-product (FB) were investigated at the laboratory and field scale. All starting materials and products were characterized by X-ray diffraction (XRD), fourier transform infrared (FFIR) spectroscopy, and elemental analyses. The results showed that the FB was strongly bound to the CCBs and could not be removed by washing. Within 2 wk of the start of a composting study, there was a rapid drop in pH from 12 to 8, an increase in temperature to 70 degrees C, and a reduction in the dissolved oxygen content, attributed to the rapid establishment of a highly active microbial population. Composting produced a soil-like material with high levels of plant nutrients, a high nutrient retention capacity, and metal contents similar to median levels of those metals reported for soils. The levels of boron and soluble salts are such that sensitive plants may initially show toxicity symptoms. However, with adequate rainfall, leaching should rapidly remove most of the B and soluble salts. With care, the material produced is safe for use as a synthetic topsoil. PMID- 11215662 TI - Nitrate removal in a riparian wetland of the Appalachian Valley and Ridge physiographic province. AB - Riparian zones within the Appalachian Valley and Ridge physiographic province are often characterized by localized variability in soil moisture and organic carbon content, as well as variability in the distribution of soils formed from alluvial and colluvial processes. These sources of variability may significantly influence denitrification rates. This investigation studied the attenuation of nitrate (NO3 -N) as wastewater effluent flowed through the shallow ground water of a forested headwater riparian zone within the Appalachian Valley and Ridge physiographic province. Ground water flow and NO3- -N measurements indicated that NO3- -N discharged to the riparian zone preferentially flowed through the A and B horizons of depressional wetlands located in relic meander scars, with NO3- -N decreasing from > 12 to < 0.5 mg L(-1). Denitrification enzyme activity (DEA) attributable to riparian zone location, soil horizon, and NO3- -N amendments was also determined. Mean DEA in saturated soils attained values as high as 210 microg N kg(-1) h(-1), and was significantly higher than in unsaturated soils, regardless of horizon (p < 0.001). Denitrification enzyme activity in the shallow A horizon of wetland soils was significantly higher (p < 0.001) than in deeper soils. Significant stimulation of DEA (p = 0.027) by N03- -N amendments occurred only in the meander scar soils receiving low NO3- -N (<3.6 mg L(-1)) concentrations. Significant denitrification of high NO3- -N ground water can occur in riparian wetland soils, but DEA is dependent upon localized differences in the degree of soil saturation and organic carbon content. PMID- 11215663 TI - Phosphorus flux from wetland soils affected by long-term nutrient loading. AB - Wetland soils play a key role in the cycling of nutrients within an ecosystem. Since soils are potentially a source or a sink for inorganic nutrients, it is important to quantify their influence on overlying water quality in order to understand their importance in overall ecosystem nutrient budgets. Laboratory and field studies were performed in the northern Everglades (WCA-2A) to determine the magnitude of phosphorus (P) flux between the soil and the overlying water column, under various redox conditions. The P flux was estimated using three techniques: intact soil cores, in situ benthic chambers, and porewater equilibrators. There was reasonable agreement between the P flux estimated using intact soil cores and benthic chambers; however, P flux estimates using the porewater equilibrators were considerably lower than the other two techniques. Models of solute flux, based solely on soil physico-chemical characteristics, may substantially underestimate soil-water nutrient exchange processes. Phosphorus flux measured with the intact soil cores varied from 6.5 mg m(-2) d(-1) near nutrient inflow areas to undetectable flux 4 km away from the inflow. Oxygen consumption varied from 4 mg m(-2) d(-1) near the inflow to a constant 1 to 2 mg m(-2) d(-1) at a distance of 4 km from the inflow. Rate of consumption of NO3- -N and SO4(2-) showed no significant trend with respect to distance from inflow. Nitrate N and SO4 consumption rates averaged 120 and 130 mg m(-1) d(-1), respectively. Consumption of O2 was correlated with P flux, whereas NO3- -N and SO4(2-) consumption were not. PMID- 11215664 TI - Alfalfa rapidly remediates excess inorganic nitrogen at a fertilizer spill site. AB - By 19%, standard remediation techniques had significantly reduced the concentration of nitrate nitrogen (NO3- -N) in local ground water at the site of a 1989 anhydrous ammonia spill, but NO3- -N concentrations in portions of the site still exceeded the public drinking water standard. Our objective was to determine whether local soil and ground water quality could be improved with alfalfa (Medicago sativa L.). A 3-yr study was conducted in replicated plots (24 by 30 m) located hydrologically upgradient of the ground water under the spill site. Three alfalfa entries ['Agate', Ineffective Agate (a non-N2-fixing elite germplasm similar to Agate), and MWNC-4 (an experimental germplasm)] were seeded in the spring of 1996. Corn (Zea mays L.) or wheat (Triticum aestivum L.) was seeded adjacent to the alfalfa each year. Crops were irrigated with N-containing ground water to meet water demand. During the 3-yr period, about 540 kg of inorganic N was removed from the aquifer through irrigation of 4.9 million L water. Cumulative N removal from the site over 3 yr was 972 kg N ha(-1) in Ineffective Agate alfalfa hay, compared with 287 kg N ha(-1) for the annual cereal grain. Soil solution NO3- concentrations were reduced to low and stable levels by alfalfa, but were more variable under the annual crops. Ground water quality improved, as evidenced by irrigation water N concentration. We do not know how much N was removed by the N2-fixing alfalfas, but it appears that either fixing or non-N2-fixing alfalfa will effectively remove inorganic N from N affected sites. PMID- 11215665 TI - Accumulation of rare earth elements in corn after agricultural application. AB - Using both pot and plot experiments, the dose-dependent accumulation of rare earth elements (REs) in corn (Zea mays L.) after application of an agricultural REs mixture was measured. In the pot experiment, the dose-dependent accumulation of REs in corn root and stem was observed, but it could not be detected in corn leaf under the dosage of 20 mg REs kg(-1) soil (oven-dry mass). The non-observed effect concentration (NOEC) for accumulation of REs in corn seedling with the pot experiment was 1.0 mg REs kg(-1). In the plot experiment, the dose-dependent accumulation was observed at an early stage after application of REs and the NOEC value of 32 mg REs m(-2) was obtained. At harvest, no dose-dependent accumulation of REs was observed in any part of the corn. These results can be confirmed by the fingerprinting analysis based on the differences between La to RE ratios in the REs mixture and in pot or plot soil. We observed that the plant shows no preference on individual RE and the results of fingerprinting indicated clearly the incorporation of exogenous REs in plant tissues, in a similar manner as that observed in the dose-dependent distribution of RE concentrations. The results indicated also a translocation process of REs from plant root to leaf when applied to soil or from leaf to root when applied to leaf. A homeostatic regulation mechanism for excessive uptake of REs in plants is suggested to regulate the concentrations of REs in the plant. PMID- 11215666 TI - Implementation of sulfate adsorption in the SAFE model. AB - An SO4(2-) adsorption submodel has been implemented in the dynamic soil chemistry model SAFE. The submodel calculates pH-dependent SO4(2-) and H+ adsorption to the soil, as well as the net surface charge development due to uneven adsorption of SO4(2-) and H+, using the empirical equations derived from an electrostatic model (Extended Constant Capacitance Model, ECCM) of SO4(2-) adsorption. The resulting new SAFE model was applied on a roof experiment plot in the Norway spruce [Picea abies (L.) H. Karst.] stand at Solling, Germany, where atmospheric S and N deposition was artificially reduced by the roof construction. The model performance was compared with the previous versions that used a pH-independent Freudlich model of SO4(2-) adsorption or assumed no SO4(2-) adsorption. With the ECCM-based SO4(2-) adsorption submodel, SAFE simulated soil solution SO4(2-) concentration and base saturation better, in comparison with measured data, than with the previous SO4(2-) adsorption formulations. Through the model application, also, need of additional improvement was suggested, such as calibration of mass transfer coefficients. PMID- 11215667 TI - Nitrogen and carbon leaching in agroecosystems and their role in denitrification potential. AB - The drainage of water and leaching of dissolved constituents represent major components of agroecosystem mass budgets that have been exceedingly difficult to measure. Equilibrium-tension lysimeters (ETLs) were used to monitor drainage, nitrogen (N), and carbon (C) leaching through Plano silt loam (fine-silty, mixed, superactive, mesic Typic Argiudoll) for a 4-yr period in a restored prairie and N fertilized no-tillage and chisel-plowed maize (Zea mays L.) agroecosystems. Mean drainage recorded during 4 yr for the prairie, no-tillage, and chisel-plowed ecosystems totaled 461, 1,116, and 1,575 mm and represented 16, 33, and 47% of precipitation plus melting of drifted snow received, respectively. Total inorganic N leaching losses during the 4-yr period for the prairie, no-tillage, and chisel-plowed ecosystems were 0.6, 201, and 179 kg N ha(-1), respectively. Inorganic N leaching represented 26 and 24% of applied fertilizer N additions to the no-tillage and chisel-plowed agroecosystems. Total dissolved C leaching losses were 119, 435, and 502 kg C ha(-1) for the prairie, no-tillage, and chisel plowed ecosystems, respectively. Sufficient dissolved organic carbon (DOC) and nitrate N (NO3- -N) existed in the prairie and agroecosystems to support subsoil denitrification. Potential denitrification, however, was limited by insufficient lengths of saturated soil conditions in all three ecosystems, the supply of DOC in the agroecosystems, and the supply of nitrate N in the prairie. Based on available DOC and nitrate N, the maximum contribution of denitrification below the root zone in the agroecosystems was less than 25% of the total amount of leached nitrate N and the probable contribution of denitrification was much less. PMID- 11215668 TI - Fate of atrazine in sandy soil cropped with sorghum. AB - A field study was conducted to determine the fate of atrazine (6-chloro-N2-ethyl N4-isopropyl-1,3,5-triazine-2,4-diamine) within the root zone (0 to 90 cm) of a sandy soil cropped with sorghum [Sorghum bicolor (L.) Moench] in Gainesville, Florida. Atrazine was uniformly applied at a rate of 1.12 kg ai. ha(-1) to a sorghum crop under moderate irrigation, optimum irrigation, and no irrigation (rainfed), 2 d after crop emergence. Bromide as a tracer for water movement was applied to the soil as NaBr at a rate of 45 kg Br ha(-1), 3 d before atrazine application. Soil water content, atrazine, and Br concentrations were determined as a function of time using soil samples taken from the root zone. Atrazine sorption coefficients and degradation rates were determined by depth for the entire root zone in the laboratory. Atrazine was strongly adsorbed within the upper 30 cm of soil and most of the atrazine recovered from the soil during the growing season was in that depth. The estimated half-life for atrazine was 32 d in topsoil to 83 d in subsoil. Atrazine concentration within the root zone decreased from 0.44 kg ai. ha(-1) 2 days after application (DAA) to 0.1 kg a.i. ha(-1) 26 DAA. Negligible amounts of atrazine (approximately 5 microg kg(-1)) were detected below the 60-cm soil depth by 64 DAA. Most of the decrease in atrazine concentration in the root zone over time was attributed to degradation. In contrast, all applied bromide had leached past the 60-cm soil depth during the same time interval. PMID- 11215669 TI - Cupric ion activity in peat soil as a toxicity indicator for maize. AB - Copper phytotoxicity in soils is difficult to assess because Cu accumulates at and damages roots, and is not readily transferred to shoots. Soil chemical properties strongly influence Cu speciation, so that total soil Cu alone is not a broadly useful indicator of potential toxicity to plants. The present study measured free Cu2+ activity in Cu-enriched peat soils using the ion selective electrode. The soil Cu2+ activity was related to the severity of phytotoxicity as measured by several indicators in a maize (Zea mays L.) bioassay, including leaf chlorosis, root stunting, and reduced shoot growth and Fe concentration. A soil Cu2+ activity of 10(-7.0) to 10(-7.5), corresponding to total Cu of about 275 mg/kg in the peat soil, caused phytotoxicity in maize seedlings. It is proposed that Cu2+ activity is more directly related to phytotoxic effects than other soil tests, such as extractions with strong acids or chelating agents, because it is the free Cu2+ in soil solution that has the most direct toxic effects on roots. There was very limited uptake of Cu into maize shoots, and even when Cu2+ activity and total soil Cu were raised into the extreme toxicity range of 10(-5) and 4,000 mg/ kg, respectively, shoot Cu remained less than 35 mg/kg. These results indicate the inadequacy of the USEPA risk assessment of potential for Cu toxicity to crops amended with sewage sludge, which assumed a no-effect level of maize shoot Cu of 40 mg/kg. PMID- 11215670 TI - Nickel increases susceptibility of a nickel hyperaccumulator to Turnip mosaic virus. AB - Hyperaccumulated Ni can defend plant tissues against herbivores and pathogens. The effectiveness of this defense, however, has not been tested with a viral pathogen. Turnip mosaic virus (TuMV) accumulation was studied in two serpentine species of Streptanthus with different Ni uptake abilities. Plants of a Ni hyperaccumulator, milk-wort jewelflower (S. polygaloides Gray), and a non hyperaccumulator, plumed jewelflower (S. insignis Jepson), were grown on Ni amended and unamended soils. Plants were inoculated with TuMV at three different phenological stages: basal rosette, bolting, and flowering. Susceptibility of experimental plants to TuMV was determined either by the magnitude of TuMV accumulation (measured by indirect enzyme-linked immunosorbent assay [ELISA]) or by plant survival. Streptanthus polygaloides plants grown on high-Ni soil were more susceptible to TuMV than low-Ni S. polygaloides at all three phenological stages. All rosette and pre-bolt S. insignis plants were infected by TuMV, but survival and TuMV accumulation were not significantly affected by soil Ni. At flowering, only high-Ni S. polygaloides plants became infected. For S. polygaloides, elevated tissue Ni concentrations enhanced TuMV infection instead of defending plants from the virus. To reduce risks to nearby agricultural crops, future phytoremed. iation and phytomining operations using this species should incorporate management plans to prevent the creation of artificial reservoirs of TuMV inoculum. PMID- 11215671 TI - Phosphate release from seasonally flooded soils: a laboratory microcosm study. AB - Phosphorus derived from agricultural practices has been targeted as a leading cause of water quality degradation in Lake Champlain. Mobilization of P from seasonally flooded agricultural soils is a concern. Using 14 soils from a research farm in New York's Champlain Valley, we characterized the available P status, extractable Fe and Al, P sorption capacities, and soluble phosphate release in flooded laboratory microcosms. Quantities of NH4-acetate available P ranged from 3 to 100 mg kg(-1) and fluoride-extractable P from 10 to 211 mg kg( 1). Flooding soils induced significant release of phosphate to the porewater over a 60- to 90-d period in 13 of the 14 soils studied. Porewater phosphate increases ranged from 2.2 to 27.0 times the initial phosphate concentrations. However, floodwater phosphate increases were much lower, with a maximum of 3.6 times the initial concentration. Average porewater phosphate concentrations over the flooding period ranged from 0.046 to 7.0 mg L(-1) and average floodwater P from 0.032 to 3.70 mg L(-1). Ammonium-acetate P and the degree of phosphorus saturation (DPS) were highly correlated with the average porewater and floodwater phosphate concentration. Average ratio of porewater to floodwater phosphate concentrations ranged from 1.0 to 3.3. Five soils that were lower in fluoride extractable P had increasing porewater phosphate accompanied by increasing porewater Fe2+ and decreasing floodwater phosphate. Results suggest that P solubility and mobility were a function of both the available P status and redox cycling. PMID- 11215672 TI - "Toxicologic pathology of the reproductive and endocrine systems". PMID- 11215673 TI - Uterine leiomyomas: mechanisms of tumorigenesis. AB - Uterine leiomyomas, also called fibroids, are the most common reproductive tract neoplasm and the leading indication for hysterectomy in premenopausal women. The discovery and development of medicinal therapies for uterine leiomyoma have been hampered by a lack of understanding regarding the etiology and molecular mechanisms underlying the development of these lesions. Although the estrogen responsiveness of uterine leiomyoma is well established, the impact of environmental estrogens and their contribution to the development of these tumors is currently unknown. The Eker rat model of uterine leiomyoma has proven useful for addressing these issues and understanding the pathophysiology of this disease. The Eker rat is the only animal model that develops spontaneous uterine leiomyomas, and these tumors share many characteristics with those found in humans. The availability of tumor-derived cell lines from these rats has made this a valuable in vitro/in vivo model system for experimental studies to investigate molecular mechanisms of disease and to design interventional and preventative strategies for this clinically relevant tumor. PMID- 11215674 TI - Genetically engineered rodent models of mammary gland carcinogenesis: an overview. AB - Breast cancer is a multifactorial disease that develops as a result of interactions among genetic, environmental, and hormonal factors. Multiple genetic derangements are believed to be involved in the pathogenesis of breast cancer, including the inactivation of tumor suppressor genes and/or the disregulation of proto-oncogenes. Age, hormones, and environmental factors further influence these genetic derangements. Spontaneous and chemically induced animal models of breast cancer have been limited in their usefulness. The advent of targeted gene mutations has allowed for a more specific exploration of the pathogenesis of breast cancer by creating mouse models that mimic single or multiple gene alterations found in human mammary tumors. The genes targeted in these models include mouse mammary tumor integration sites and genes that encode for growth regulators, signal transduction proteins, cell cycle proteins, and cell matrix proteinases. In this review, I summarize tumor morphology and the relevance of each model to the pathogenesis and progression of human breast cancer. These models have great potential for elucidating the multistep process of mammary gland carcinogenesis and for contributing to the identification of novel therapeutic targets. PMID- 11215675 TI - Mammary tumor induction and premature ovarian failure in ApcMin mice are not enhanced by Brca2 deficiency. AB - Inherited BRCA2 mutations predispose individuals to breast cancer and increase risk at other sites. Recent studies have suggested a role for the APC I1307K allele as a low-penetrance breast cancer susceptibility gene that enhances the phenotypic effects of BRCA1 and BRCA2 mutations. To model the consequences of inheriting mutant alleles of the BRCA2 and APC tumor suppressor genes, we examined tumor outcome in C57BL/6 mice with mutations in the Brca2 and Apc genes. We hypothesized that if the Brca2 and Apc genes were interacting to influence mammary tumor susceptibility, then mammary tumor incidence and/or multiplicity would be altered in mice that had inherited mutations in both genes. Female and male offspring treated with a single IP injection of 50 mg/kg N-ethyl-N nitrosourea (ENU) at 35 days of age developed mammary adenoacanthomas by 100 days of age. The female Apc-mutant and Brca2/Apc double-mutant progeny had mean mammary tumor multiplicities of 6.7+/-2.8 and 7.2+/-2.7, respectively, compared to wild-type and Brca2-mutant females, which had mean mammary tumor multiplicities of 0.1+/-0.4 and 0.3+/-0.5, respectively. Female ENU-treated Apc mutant and Brca2/Apc double heterozygotes were also susceptible to premature ovarian failure. Thus, the inheritance of an Apc mutation predisposes ENU-treated female and male mice to mammary tumors and, in the case of female mice, to ovarian failure. These results indicate that mammary tumor development in Apc mutant mice can progress independently of ovarian hormones. The Apc mutation driven phenotypes were not modified by mutation of Brca2, perhaps because Brca2 acts in a hormonally dependent pathway of mammary carcinogenesis. PMID- 11215677 TI - Cancer prevention studies in p53-deficient mice. AB - Future progress in mechanism-based cancer prevention research may be facilitated by animal models displaying specific genetic susceptibilities for cancer, such as mice deficient in 1 (+/-) or both (-/-) alleles of the p53 tumor suppressor gene. We observed in p53-/- mice that calorie restriction (CR) increased the latency of spontaneous tumor development (mostly lymphomas) by approximately 75%, decreased serum insulin-like growth factor-1 (IGF-1) and leptin levels, slowed thymocyte cell cycle traverse, and induced apoptosis in immature thymocytes. In p53+/- mice, CR and a 1 d/wk fast each delayed spontaneous tumor development (a mix of lymphomas, sarcomas, and epithelial tumors) and decreased serum IGF-1 and leptin levels, even when begun late in life. In p53+/-Wnt-1 transgenic mice, a mammary tumor model, the same interventions increased mammary tumor latency and reduced mean serum IGF-1 and leptin levels to <50% of those of control mice. We capitalized on the susceptibility of p53+/- mice to chronic, low-dose aromatic amine-induced bladder carcinogenesis to develop a useful model for evaluating bladder cancer prevention approaches. These examples clearly indicate that mice with specific (and humanlike) genetic susceptibilities for cancer are powerful models for testing interventions that may inhibit carcinogenesis in humans. PMID- 11215676 TI - The effect of short intermittent light exposures on the melatonin circadian rhythm and NMU-induced breast cancer in female F344/N rats. AB - We investigated the effects of altered endogenous nighttime melatonin concentrations on mammary tumor production in an N-nitroso-N-methylurea (NMU) induced breast cancer model in female Fischer 344 (F344)/N rats. Experiments were designed 1) to evaluate whether short-duration intermittent exposures to light at night would affect the nocturnal rise of melatonin, resulting in a decrease in nighttime serum melatonin concentrations, 2) to evaluate whether any suppression of nighttime serum melatonin concentrations could be maintained for a period of weeks, and 3) to determine the effects of suppressed serum melatonin concentrations on the incidence and progression of NMU-induced breast cancer. In vivo studies were used to assess serum melatonin concentrations after 1 day and 2 and 10 weeks of nightly administration of short-duration intermittent light exposure at night and incidence of NMU-induced tumors. Five 1-minute exposures to incandescent light every 2 hours after the start of the dark phase of the light: dark cycle decreased the magnitude of the nocturnal rise of serum melatonin concentrations in rats by approximately 65%. After 2 weeks of nightly intermittent light exposures, an average decrease of the peak nighttime serum melatonin concentrations of approximately 35% occurred. The amelioration continued and, at 10 weeks, peak nighttime serum melatonin concentrations were still decreased, by approximately 25%. Because peak endogenous nighttime serum melatonin values could be moderately suppressed for at least 10 weeks, a 26-week NMU mammary tumor study was conducted. Serum melatonin concentrations and incidence, multiplicity, and weight of NMU-induced mammary tumors were assessed. A group of pinealectomized (Px) animals was also included in the tumor study. No effect on the development of mammary tumors in an NMU-induced tumor model in rats occurred when endogenous nighttime serum melatonin concentrations were moderately suppressed by short-duration intermittent light exposures at night. At necropsy, there were no alterations in mammary tumor incidence (28/40 NMU controls, 28/40 NMU + light, 31/40 NMU + Px), multiplicity (2.18 tumors/tumor-bearing NMU control, 1.89 NMU + light, 2.39 NMU + Px), or average tumor weight (1.20 g NMU control, 1.19 g NMU + light, 0.74 g NMU + Px). Tumor burden had no effect on the serum melatonin cycle. At 26 weeks, however, animals exposed to intermittent light at night exhibited approximately 3-fold higher serum melatonin concentrations as compared with controls. Additionally, rats that had been pinealectomized at 4 weeks of age had serum melatonin concentrations that were markedly higher than the expected baseline concentrations for pinealectomized rats (<15 pg/ml), suggesting the reestablishment of a melatonin cycle. This finding was unexpected and suggests that melatonin can be produced by an organ or tissue other than the pineal gland. PMID- 11215678 TI - Naturally occurring and experimental diabetes in cynomolgus monkeys: a comparison of carbohydrate and lipid metabolism and islet pathology. AB - Diabetes is a major health problem of increasing incidence in the United States. Diabetes research has been limited by lack of availability of good animal models, particularly for the study of comorbidities associated with diabetes. We investigated the use of cynomolgus monkeys as an animal model of both type 1 and type 2 diabetes and compared these naturally occurring diseases with streptozotocin-induced diabetes. Both type 1 diabetics and streptozotocin-induced diabetics present with sudden onset of hyperglycemia and are ketosis prone without exogenous insulin. Type 2 diabetics can have a very long period of moderate hyperglycemia and hypertriglyceridemia and only require exogenous insulin therapy if pancreatic islet reserves are depleted. Type 2 diabetes is preceded by a relatively long period of insulin resistance that is associated with obesity and dyslipidemia. As insulin resistance progresses, islet size and insulin content increases initially. However, with sustained periods of insulin resistance, islet amyloid polypeptide (IAPP) is deposited in islets and can replace normal islet architecture, resulting in an insulin-deficient state. Appearance of IAPP also occurs in human type 2 diabetics but not in conventional rodent models. Unlike type 2 diabetes, neither type 1 nor streptozotocin-induced diabetes is associated with IAPP. Rather, islets can appear normal histologically, but have decreased insulin secretion and immunostaining. Further, the amount of insulin present in the islet is correlated with plasma insulin levels following glucose challenge. Studies are ongoing to determine the pathogenic changes associated with the progression of diabetes and to find novel drug treatments for diabetics. PMID- 11215680 TI - Summary of panel discussion: past, present and future of toxicologic pathologists and the contributions to hazard identification and molecular mechanisms of action. AB - One of the major roles for the toxicologic pathologists now and into the future will be to determine the biologic significance of chemically induced biochemical and molecular alterations detected in whole tissue homogenates or cell cultures. The biologically significant effects will then require further analysis to determine their relevance to human health effects. The challenge is to train pathologists for toxicologic and molecular pathology experience without diluting basic pathology skills. Programs and approaches reviewed and suggested during the panel discussion should provide ideas and the impetus for those in a position to engage in similar activities. PMID- 11215679 TI - Role of thyroid hormones in hepatic effects of peroxisome proliferators. AB - Peroxisome proliferators are endocrine disrupting chemicals that cause liver tumors in rodents but not humans. Although the receptor that mediates key hepatic effects, the peroxisome proliferator-activated receptor alpha (PPAR-alpha), and its endogenous ligands have been identified, the mechanism whereby these commonly used chemicals cause liver tumors in rodents has yet to be elucidated. Species differences in PPAR-alpha and DNA response elements may explain some of the variability in response upon exposure to peroxisome proliferators. The possibility that thyroid-modulating effects of peroxisome proliferators may contribute to the hepatic effects of peroxisome proliferators has yet to be fully explored. When the potent peroxisome proliferator, WY-14,643, was given to hypothyroid rats, there was a blunting of the hepatomegaly and hepatocyte proliferative responses seen in thyroid-intact animals. Acyl-CoA oxidase activity was unaltered by changes in thyroid hormone status. In addition, preliminary evidence indicates that peroxisome proliferators increased hepatic thyroid receptor (TRalpha1) expression, but TRalpha1 levels in liver tumors were similar to those in unexposed animals. Significant differences between humans and rodents with respect to thyroid hormone physiology and metabolism, in conjunction with the results of these studies, may be indicative of yet another mechanism to explain differential sensitivity to hepatic effects of peroxisome proliferators. PMID- 11215681 TI - Regulation of xenobiotic metabolism by orphan nuclear receptors. AB - Nuclear receptors control gene transcription by binding to specific promoter regions of DNA in the presence of ligand. Orphan nuclear receptors are nuclear receptors for which the endogenous ligand(s) has yet to be identified. Systematic evaluation of orphan nuclear receptors can elucidate species differences in xenobiotic metabolism in addition to aiding in identification of endogenous ligands. The receptor-binding affinity and specificity of various chemicals, with subsequent determination of the genes controlled by nuclear receptors, are goals of investigations into orphan nuclear receptor structure/function and can provide valuable tools in predicting drug interactions and toxicity. PMID- 11215682 TI - Effects of microsomal enzyme inducers on thyroid follicular cell proliferation and thyroid hormone metabolism. AB - The effects of microsomal enzyme inducers on thyroid hormone homeostasis and the thyroid gland are of concern. We have investigated the effects of microsomal enzyme inducers on thyroid follicular cell proliferation and thyroid hormone metabolism in rats. We have shown that small increases in serum TSH can result in large increases in thyroid follicular cell proliferation. Furthermore, only those microsomal enzyme inducers that increase serum TSH--that is, phenobarbital (PB) and pregnenolone-16alpha-carbonitrile (PCN)-increase thyroid follicular cell proliferation, whereas those microsomal enzyme inducers that do not increase serum TSH--that is, 3-methylcholanthrene (3MC) and Aroclor 1254 (PCB)-do not increase thyroid follicular cell proliferation. Deiodination does not appear to be the reason why serum T3 concentrations are maintained in microsomal enzyme inducer-treated rats. We have also shown that those microsomal enzyme inducers that increase serum TSH increase T3 UDP-glucuronosyltransferase (UGT) activity, whereas those microsomal enzyme inducers that do not increase serum TSH do not increase T3 UGT activity. This finding suggests that induction of T3 glucuronidation, rather than T4 glucuronidation, mediates increases in serum TSH of microsomal enzyme inducer treated rats. PMID- 11215683 TI - Adrenal gland: structure, function, and mechanisms of toxicity. AB - The adrenal gland is one of the most common endocrine organs affected by chemically induced lesions. In the adrenal cortex, lesions are more frequent in the zona fasciculata and reticularis than in the zona glomerulosa. The adrenal cortex produces steroid hormones with a 17-carbon nucleus following a series of hydroxylation reactions that occur in the mitochondria and endoplasmic reticulum. Toxic agents for the adrenal cortex include short-chain aliphatic compounds, lipidosis inducers, amphiphilic compounds, natural and synthetic steroids, and chemicals that affect hydroxylation. Morphologic evaluation of cortical lesions provides insight into the sites of inhibition of steroidogenesis. The adrenal cortex response to injury is varied. Degeneration (vacuolar and granular), necrosis, and hemorrhage are common findings of acute injury. In contrast, chronic reparative processes are typically atrophy, fibrosis, and nodular hyperplasia. Chemically induced proliferative lesions are uncommon in the adrenal cortex. The adrenal medulla contains chromaffin cells (that produce epinephrine, norepinephrine, chromogranin, and neuropeptides) and ganglion cells. Proliferative lesions of the medulla are common in the rat and include diffuse or nodular hyperplasia and benign and malignant pheochromocytoma. Mechanisms of chromaffin cell proliferation in rats include excess growth hormone or prolactin, stimulation of cholinergic nerves, and diet-induced hypercalcemia. There often are species specificity and age dependence in the development of chemically induced adrenal lesions that should be considered when interpreting toxicity data. PMID- 11215684 TI - Overview of male reproductive pathology. AB - An understanding of form and function is important for examination of the male reproductive tract. A basic understanding of spermatogenesis and hormonal function in the reproductive tract is essential for the pathologists in this evaluation. Gross and histologic reproductive changes need to be distinguished from normal variation and correlated with the reproductive status of the animal. This is especially important when correlating histologic changes with organ weight and other reproductive parameters, such as seminal analysis data. Sexual maturity of animals and tissue handing can impact interpretation. Sexual immaturity of preclinical safety animals can present challenges for accurate identification of compound-related changes. Likewise, proper handling of unfixed reproductive tissues and appropriate selection of a fixation protocol are important in avoiding artifacts that may interfere with the microscopic evaluation. The histopathology technician needs to recognize testicular landmarks that allow for correct orientation at trimming so the pathologist can assess not only the morphology of seminiferous tubules but also the outflow tract. For the most effective evaluation of the male reproductive tract, the testes and epididymides should be examined concurrently. Although the term "staging" is often used inappropriately, the pathologist should review testicular tissues in a "stage-aware" manner. This article reviews gross and histologic changes of the male reproductive tract as well as tissue orientation and fixation to assist in accurate interpretation of potential treatment-related changes in male reproduction. PMID- 11215685 TI - Molecular basis of dioxin actions: evidence supporting chemoprotection. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin), a highly publicized environmental contaminant, was shown to be chemoprotective against breast cancer in both rats and mice in bioassays conducted in the late 1970s. This finding went largely unnoticed as investigators focused on animal tumors that were increased by dioxin. The position that dioxin causes human tumors remains a subject for debate; however, recent epidemiological studies of a population highly exposed to dioxin in 1976 as a result of an industrial accident suggest that women with higher dioxin body burdens may have a lower incidence of breast cancer. With the growth of new knowledge about the molecular basis of dioxin actions in humans and animals, it is clear that most of the responses produced by this agent are initiated by a specific recognition protein (designated the Ah receptor) found in almost all animal and human tissues and organs. The recognition event between the Ah receptor and environmental agents like dioxin is due to the formation of a complex. We have observed that in the presence of dioxin, the Ah receptor turns off proliferation in tumor cells and suppresses the ability of these cells to invade normal tissue. We believe that these findings provide a molecular and biochemical basis for understanding the chemoprotective mechanisms suggested by the findings of rodent bioassays and could lead to the development of novel therapeutic agents targeting the Ah receptor. PMID- 11215686 TI - Pathogenesis of male reproductive toxicity. AB - Toxicologic disturbance of male reproductive function can occur at many sites and produce a range of effects, some primary and some secondary to the initial insult. The challenge to the toxicological pathologist is to identify the primary site of damage and provide an insight into the pathogenesis of the morphologic lesion or functional deficit. Target sites include the testis, the epididymis, the mature sperm, and the hormonal regulatory system. Detection of effects at these varied sites requires the measurement of multiple endpoints only 1 of which is histopathology, but once identified, careful microscopic examination of the early changes in lesion development can provide essential information on the probable target cell and possible mechanisms of toxicity. Chemicals that affect different cell types or specific cellular functions generally elicit predictable patterns of pathological changes that can be readily recognized. Understanding the pathogenesis, the likely reversibility and the significance of reproductive tract lesions is aided by a sound knowledge of the physiology of the testis and epididymis and, in particular, an understanding of the timing of sperm production and transport. PMID- 11215687 TI - Reproductive endocrinology and toxicological pathology over the life span of the female rodent. AB - Understanding the pathology of the female reproductive system with respect to toxicology requires a basic understanding of morphology and function of the system over time because the nature of the female reproductive system is cyclical. Thus, the morphology and the endocrinology is dependent on age and time, as form follows function and function follows form. The life span of the rodent is used as an outline to present an overview of key morphological and endocrinological events important for toxicologic pathologists to consider in study evaluations. Environmental and pharmaceutical compounds differentially impact the organs individually and/or the system in its entirety in a time- and dose-dependent way. Examples are used to illustrate the consequences of exposures at different times and with different outcomes. PMID- 11215688 TI - Overview of structural and functional lesions in endocrine organs of animals. AB - The objective of this review is to summarize the pathogenic mechanisms responsible for perturbations of endocrine function and development of structural lesions that result in important diseases in domestic and laboratory animals. For each major category, several specific disease problems have been selected to illustrate the functional and morphologic lesions that are characteristic for either a naturally occurring endocrinopathy or endocrine disturbances induced by the administration of large doses of xenobiotic chemicals. The major pathogenic mechanisms responsible for disruption of endocrine function include primary hyperfunction, secondary hyperfunction, primary hypofunction, secondary hypofunction, endocrine hyperactivity secondary to other conditions, hypersecretion of hormones by nonendocrine tumors, failure of target cells to respond to a hormone, failure of fetal endocrine function, abnormal degradation (increased or decreased rate) of hormone, and iatrogenic syndromes of hormone excess (direct and indirect). Disorders of the endocrine system are encountered in a wide variety of domestic and laboratory animal species and often present challenging diagnostic problems. The development of proliferative lesions, usually hyperplasia and benign tumors, in endocrine organs and hormone-responsive tissues are common findings in chronic studies with high doses of many nongenotoxic xenobiotic chemicals administered to sensitive rodent species and may have limited significance for human safety assessment. PMID- 11215689 TI - Assessment of hormonally active agents in the reproductive tract of female nonhuman primates. AB - Using the ovariectomized macaque model of postmenopausal women's health, we investigated the effects of long-term treatments (5 weeks-3 years) with estradiol, conjugated equine estrogens (CEE), esterified estrogens, progestins such as medroxyprogesterone acetate (MPA) and nomegestrol acetate, CEE + MPA, tamoxifen, soybean phytoestrogens (SPEs), a variety of putative selective estrogen receptor modulators (SERMs), and androgens. Agents tested were selected on the basis of beneficial effects on arteries and/or bone. Doses were scaled on a caloric or serum-concentration basis to approximate human clinical doses. We evaluated endometrial and mammary gland histopathology and morphometry and used immunohistochemistry to evaluate cell proliferation and expression of estrogen receptor alpha and progesterone receptor (PR). Both estradiol and CEE induced endometrial hyperplasia. MPA antagonized epithelial proliferation induced by CEE in endometrium and induced pseudodecidual stromal hyperplasia in some animals. Tamoxifen induced endometrial polyps, cystic hyperplasia, stromal fibrosis, and PR expression but not Ki-67 expression. SPEs were not estrogenic at dietary doses and antagonized estrogen-induced proliferation in the endometrium and breast. Nandrolone induced mucometra and an adenomyosis-like change. The potential SERM 17 alpha dihydroequilenin did not have uterotrophic or mammotrophic effects. In general, experimental findings in macaques have been predictive of outcomes in human clinical trials of the same agents. PMID- 11215690 TI - Ovarian toxicity of 4-vinylcyclohexene diepoxide: a mechanistic model. AB - Female mammals are born with a finite number of ovarian primordial follicles that cannot be regenerated; thus, chemicals that destroy oocytes contained in these follicles can produce premature ovarian failure (early menopuase in women). Exposure of women to known ovotoxicants, such as contaminants in cigarette smoke, is associated with early menopause. Thus, the potential risks posed by ovotoxic chemicals is of concern. Our studies have focused on the environmental chemical 4 vinylcyclohexene (VCH), which is produced during the manufacture of rubber tires, flame retardants, insecticides, plasticizers, and antioxidants. Dosing of female rats and mice with the ovotoxic diepoxide metabolite of VCH, 4-vinylcyclohexene diepoxide (VCD), for 30 days destroyed the majority of ovarian primordial follicles. Using VCD in rats as a generalized model for ovotoxicity, we determined that 1) repeated daily dosing is required, 2) cell death is via apoptosis, and 3) altered expression of specific genes is involved. An integrated approach at the morphologic, biochemical, and molecular level was used to support these conclusions. Studies in isolated rat small preantral follicles (targeted for VCD-induced ovotoxicity) focused on the role of cell death genes, mitochondrion-associated events, and VCD metabolism. We also evaluated how this information relates to human risk for early menopause. These animal research results provide a better understanding of the potential risk of human exposure to environmental ovarian toxicants and greater insight as to the impact of these toxicants on reproductive health in women. PMID- 11215691 TI - Synthetic vitreous fibers: a review of toxicology research and its impact on hazard classification. AB - Because the inhalation of asbestos, a naturally occurring, inorganic fibrous material, is associated with lung fibrosis and thoracic cancers, concerns have been raised about the possible health effects of synthetic vitreous fibers (SVFs). SVFs include a very broad variety of inorganic fibrous materials with an amorphous molecular structure. Traditionally, SVFs have been divided into three subcategories based on composition: fiberglass, mineral wool (rock, stone, and slag wools), and refractory ceramic fiber. For more than 50 years, the toxicologic potential of SVFs has been researched extensively using human epidemiology and a variety of laboratory studies. Here we review the research and its impact on hazard classification and regulation of SVFs. Large, ongoing epidemiology studies of SVF manufacturing workers have provided very little evidence of harmful effects in humans. Several decades of research using rodents exposed by inhalation have confirmed that SVF pulmonary effects are determined by the "Three D's", fiber dose (lung), dimension, and durability. Lung dose over time is determined by fiber deposition and biopersistence in the lung. Deposition is inversely related to fiber diameter. Biopersistence is directly related to fiber length and inversely related to fiber dissolution and fragmentation rates. Inhaled short fibers are cleared from the lung relatively quickly by mobile phagocytic cells, but long fibers persist until they dissolve or fragment. In contrast to asbestos, most of the SVFs tested in rodent inhalation studies cleared rapidly from the lung (were nonbiopersistent) and were innocuous. However, several relativley biopersistent SVFs induced chronic inflammation, lung scarring (fibrosis), and thoracic neoplasms. Thus, biopersistence of fibers is now generally recognized as a key determinant of the toxicologic potential of SVFs. In vitro dissolution of fibers in simulated extracellular fluid correlates fairly well with fiber biopersistence in the lung and pulmonary toxicity, but several exceptions suggest that biopersistence involves more than dissolution rate. Research demonstrating the relationship between biopersistence and SVF toxicity has provided a scientific basis for hazard classification and regulation of SVFs. For a nonhazardous classification, legislation recently passed by the European Union requires a respirable insulation wool to have a low lung biopersistence or be noncarcinogenic in laboratory rats. U.S. fiberglass and mineral wool industries and the Occupational Health and Safety Administration (OSHA) have formed a voluntary Health and Safety Partnership Program (HSPP) that include: a voluntary permissible exposure level (PEL) in the workplace of 1 fiber/cc, a respiratory protection program for specified tasks, continued workplace air monitoring, and, where possible, the development of fiber formulations that do not persist in the lung. RCF manufacturers have implemented a Product Stewardship Program that includes: a recommended exposure guideline of 0.5 fibers/cc; a 5-year workplace air monitoring program; and research into the development of high-temperature-resistant, biosoluble fibers. PMID- 11215692 TI - Paracetamol (acetaminophen)-induced toxicity: molecular and biochemical mechanisms, analogues and protective approaches. AB - An overview is presented on the molecular aspects of toxicity due to paracetamol (acetaminophen) and structural analogues. The emphasis is on four main topics, that is, bioactivation, detoxication, chemoprevention, and chemoprotection. In addition, some pharmacological and clinical aspects are discussed briefly. A general introduction is presented on the biokinetics, biotransformation, and structural modification of paracetamol. Phase II biotransformation in relation to marked species differences and interorgan transport of metabolites are described in detail, as are bioactivation by cytochrome P450 and peroxidases, two important phase I enzyme families. Hepatotoxicity is described in depth, as it is the most frequent clinical observation after paracetamol-intoxication. In this context, covalent protein binding and oxidative stress are two important initial (Stage I) events highlighted. In addition, the more recently reported nuclear effects are discussed as well as secondary events (Stage II) that spread over the whole liver and may be relevant targets for clinical treatment. The second most frequent clinical observation, renal toxicity, is described with respect to the involvement of prostaglandin synthase, N-deacetylase, cytochrome P450 and glutathione S-transferase. Lastly, mechanism-based developments of chemoprotective agents and progress in the development of structural analogues with an improved therapeutic index are outlined. PMID- 11215693 TI - Severe canine hereditary hemolytic anemia treated by nonmyeloablative marrow transplantation. AB - Severe hemolytic anemia in Basenji dogs secondary to pyruvate kinase (PK) deficiency can be corrected by marrow allografts from healthy littermates after a conventional high-dose myeloablative conditioning regimen. The nonmyeloablative conditioning regimen used here, which consisted of a sublethal dose of 200 cGy total body irradiation before and immunosuppression with mycophenolate mofetil and cyclosporine after a dog leukocyte antigen (DLA)-identical littermate allograft, has been found to be effective in establishing stable mixed donor/host hematopoietic chimerism in normal dogs. We explored the feasibility of nonmyeloablative marrow allografts for the treatment of canine PK deficiency and studied the effect of stable allogeneic mixed hematopoietic chimerism on the natural course of the disease. Five affected dogs received transplants, of which 3 dogs had advanced liver cirrhosis and myelofibrosis. Both complications were presumed to be due to iron overload. All 5 dogs showed initial engraftment. Two rejected their grafts after 6 weeks but survived with completeautologous marrow recovery and return of the disease. One died from liver failure on day 27 with 60% donor engraftment. Two dogs have shown sustained mixed donor/host chimerism for more than a year with 85% and 12% donor hematopoietic cells, respectively. Overall clinical response correlated with the degree of donor chimerism. The dog with the low degree of chimerism achieved partial resolution of hemolysis, but the disease symptoms persisted as manifested by increasing iron overload resulting in progression of marrow and liver fibrosis. The dog with the high degree of donor chimerism achieved almost complete resolution of hemolysis with a decrease of marrow iron content and resolution of marrow fibrosis. These observations suggest that mixed hematopoietic chimerism can be relatively safely established in dogs with PK deficiency even in the presence of advanced liver cirrhosis. However, although effective in correcting or delaying the development of myelofibrosis, a low degree of mixed chimerism was not sufficient to prevent continued hemolysis of red blood cells of host origin. Complete donor chimerism appears necessary to achieve a long-term cure. PMID- 11215694 TI - Vbeta spectratype analysis reveals heterogeneity of CD4+ T-cell responses to minor histocompatibility antigens involved in graft-versus-host disease: correlations with epithelial tissue infiltrate. AB - Lethal graft-versus-host disease (GVHD) can be induced after hematopoietic stem cell transplantation between major histocompatibility complex-matched murine strains expressing multiple minor histocompatibility antigen (miHA) differences. In the C57BL/6By (B6)-->C.B10-H2b/LiMcdJ (BALB.B) irradiation model, both CD4+ and CD8+ donor T cells can mediate lethal GVHD, whereas in the B6-->CXB-2/By (CXBE) model, in which the recipient expresses a subset of BALB.B miHA, only the CD8+ T cells are lethal. Phenotypic analysis of CD4+ T cells collected from the thoracic duct lymphocyte pool of recipient mice had indicated expansion of the donor T-cell receptor Vbeta6-9 families in BALB.B recipients, and only Vbeta7 and Vbeta9 populations in CXBE mice. CDR3-size spectratyping, used to further analyze these responses, revealed overlapping oligoclonal expansion of Vbeta4, Vbeta6-10, and Vbeta12-14 families in both BALB.B and CXBE recipients injected with host presensitized B6 T cells. In addition, the B6-->BALB.B CD4+ T-cell response appeared to involve the recognition of unique BALB.B-specific miHA, indicated by additional skewing of Vbeta2 and Vbeta11 families. On the other hand, the B6- >CXBE strain combination exhibited unique skewing of the Vbeta16 and Vbeta18 families. Immunohistochemical staining of lingual epithelial sections from BALB.B recipients of naive B6 CD4+ T cells correlated with the involvement of several of the spectratype-skewed Vbeta families in GVHD lesions. Furthermore, magnetic cell separation techniques were used to positively select the spectratype-skewed Vbeta families from the donor B6 CD4+ T cells; the former were found to have significant GVHD potential upon transplantation into lethally irradiated BALB.B recipients. In contrast, mice that received transplants from the unskewed Vbeta families all survived with minimal symptoms of GVHD. Taken together, these results demonstrate that the expansion of particular Vbeta families, as identified by spectratype analysis, correlates with the induction and pathogenesis of lethal GVHD. PMID- 11215695 TI - Modulation of graft-versus-tumor effects in a murine allogeneic bone marrow transplantation model by tumor-derived transforming growth factor-betaI. AB - Although graft-versus-leukemia effects in allogeneic bone marrow transplantation (alloBMT) are well documented, graft-versus-tumor (GVT) effects are poorly defined. To investigate the latter, we established a murine model of breast cancer using TS/A, a transforming growth factor (TGF)-beta1-secreting breast cancer cell line of BALB/c origin. In the setting of disparate (parent into F1) alloBMT, no appreciable GVT was identified. To assess whether TGF-beta1 secreted by the tumor might inhibit the antitumor response, TGF-beta1 antisense vector was transfected into the TS/A breast cancer cell line. Mice were inoculated with either TGF-beta1 antisense transfected or the mock transfected cell line and underwent syngeneic or alloBMT. No evidence of GVT was appreciated for the mock transfected breast cancer cell line as assessed by an absence of a statistically significant difference in survival between syngeneic and alloBMT groups. However, there was a highly statistically significant survival difference between allogeneic versus syngeneic bone marrow transplantation groups inoculated with the TGF-beta1 antisense-transfected cell line (P = .00001) as well as when comparing the survival of mice that received alloBMT for TGF-beta1 antisense transfected tumor versus mock-transfected tumor (P = .0008). These data suggest that (1) GVT exists against the antisense-transfected breast cancer cells in this experimental model and (2) TGF-beta1 may be involved in suppressing antitumor responses in the setting of alloBMT for breast cancer. PMID- 11215696 TI - The role of disease stage in the response to donor lymphocyte infusions as treatment for leukemic relapse. AB - Between 1991 and 1999, 44 leukemic patients received donor lymphocyte infusions (DLIs) at our center (22 patients with chronic myelogenous leukemia [CML]; 10 with acute myelogenous leukemia; 11 with acute lymphatic leukemia; and 1 with myelodysplastic syndrome). Seventeen patients received graft-versus-host disease (GVHD) prophylaxis with methotrexate (MTX) at the time of DLI. In CML patients, 15 of 22 (68%) re-entered complete remission after DLI. At 3 years post-DLI, patients with cytogenetic (n = 10) or molecular (n = 3) relapse had a current leukemia-free survival (cLFS) rate of 85% compared with 0% for patients with hematologic relapse (P < .001). Among 15 CML patients who initially responded to DLI, 4 patients relapsed within the first 2 years. Four of 16 patients (25%) with acute leukemia had an initial response with complete remission after DLI. Two of them subsequently relapsed within 1 year. Patients with acute leukemia who relapsed within 1 year of hematopoietic stem cell transplantation (n = 9) had 0% cLFS at 18 months; patients with later relapse had 29% cLFS (P = .015). The overall probability of cLFS at 3 years for CML patients was 46%. For other diseases, cLFS was 13% at 18 months after DLI. Patients who developed chronic GVHD secondary to DLI showed a 3-year cLFS of 51% compared with 18% for patients without chronic GVHD (P = .022). This study emphasizes the importance of early disease stage and presence of chronic GVHD for effective DLI. PMID- 11215698 TI - Assessment of barriers to bone marrow donation by unrelated African-American potential donors. AB - African Americans have a lower registration rate for becoming potential bone marrow and stem cell donors. The same attitudes and behaviors are exhibited in regard to solid organ and blood donations, causing a serious under-representation of the African-American population in the donor pool. In our efforts to increase donor availability for African Americans through a project funded by the Medical University of South Carolina, we used a survey to determine the reasons African Americans do not participate as donors for bone marrow. We surveyed 589 African Americans, a great majority of whom were women. Our survey identified major barriers to donation to be the lack of awareness that transplantation can save lives, the cost of donation, and the lack of opportunities to donate. The most effective interventions in increasing donation have been to provide both educational programs preceding marrow drives and the opportunity to donate. Through these efforts, the number of potential African-American donors has increased from 768 (accrued over a period of 12 years) to 1977 in less than 2 years. We conclude that a minority recruitment program targeting African-American volunteers for the National Marrow Donor Program (NMDP) should include an education component addressing the most common barriers before drives. PMID- 11215697 TI - Cyclophosphamide and antithymocyte globulin to condition patients with aplastic anemia for allogeneic marrow transplantations: the experience in four centers. AB - This report summarizes the experience with a conditioning regimen of cyclophosphamide and antithymocyte globulin in patients with severe aplastic anemia given HLA-matched related marrow grafts at 4 transplantation centers. Enrolled were 94 consecutive patients, of whom 87 had received multiple transfusions and 38 had failed immunosuppressive therapy. Their ages ranged from 2 to 59 years. After transplantation, 89 patients received a methotrexate/cyclosporine regimen for graft-versus-host disease (GVHD) prevention. Cyclosporine with or without prednisone was given in 4 patients, and no immunosuppression was given in 1 patient. Ninety-six percent of patients had sustained grafts, whereas 4% rejected grafts between 2 and 7 months after transplantation. Of the 4 rejecting patients, 3 are alive with successful second engraftments. Acute grade II GVHD was seen in 21% of patients, grade III in 7%, and grade IV in 1% of patients. Chronic GVHD was seen in 32% of patients, most of whom responded completely to immunosuppressive therapy. With a median follow-up of 6.0 years (range, 0.5-11.6 years), the survival rate was 88%. No unusual long term side effects have been seen with the regimen. We conclude that the cyclophosphamide/antithymocyte globulin regimen combined with methotrexate/cyclosporine after transplantation is well tolerated and effective in heavily pretreated patients with aplastic anemia. PMID- 11215699 TI - High-dose therapy and autologous hematopoietic cell transplantation in children with primary refractory and relapsed Hodgkin's disease: atopy predicts idiopathic diffuse lung injury syndromes. AB - The use of high-dose therapy (HDT) and autologous hematopoietic cell transplantation (AHCT) for children and adolescents with primary refractory and relapsed Hodgkin's disease is increasing. The purpose of this retrospective analysis was to: (1) evaluate the outcome of HDT and AHCT in pediatric patients with Hodgkin's disease, and (2) identify factors that predispose patients to the development of transplantation-related complications. We describe the experiences of 34 pediatric patients from a single institution with primary refractory or relapsed Hodgkin's disease. HDT regimens consisted of cyclophosphamide and etoposide combined with either carmustine, chloroethylcyclohexylnitrosurea, or fractionated total body irradiation. Kaplan-Meier survival predicts that 67% (95% confidence interval [CI] 47%-87%) of patients will be alive and disease-free at 5 years. Nine patients had disease recurrence, of whom 5 relapsed after 1 year (1.5 6.3 years). Five patients succumbed to treatment-related toxicities, of whom 4 died of pulmonary failure. Fifteen patients (44%) developed post-AHCT idiopathic diffuse lung injury syndrome: acute alveolitis (n = 2); diffuse alveolar hemorrhage (n = 2); acute respiratory distress syndrome (n = 2); delayed interstitial pneumonitis (n = 8); and bronchiolitis obliterans (n = 1). The following factors did not predict for the development of a diffuse lung injury syndrome in univariate analysis: prior treatment with bleomycin, pre-HDT pulmonary function tests, and prior thoracic irradiation. Of the patients in our cohort, 44% had a history of atopy (allergic rhinitis and/or asthma). Multivariate logistic analysis revealed that a preexisting history of atopy was highly predictive of idiopathic pulmonary complications (P = .0001, odds ratio = 21, CI 3.6-125). Our experience shows that HDT followed by AHCT results in durable remissions in two thirds of pediatric patients with refractory and relapsed Hodgkin's disease, and a history of atopy is associated with post-AHCT pulmonary complications. PMID- 11215700 TI - Stress-inducible DNA repair in Saccharomyces cerevisiae. AB - Saccharomyces cerevisiae shows altered radiation response under various stress conditions, such as nutrition depletion, nitrogen starvation, osmotic shock, heat shock, and mild chemical treatments. In general, the cells show higher levels of UV or gamma radiation resistance under the stress. However, not all the stress conditions affect the repair system in the same manner. For example, depletion of nitrogen supply in the growth medium has been shown to enhance the repair of gamma ray-induced DNA damage without significantly affecting the UV response of the cells. On the other hand, a mild treatment with alkali or hydrogen peroxide improves the response to UV light but not to gamma radiation. It has further been shown that the effect of these stresses are not additive, e.g., the alkali and hydrogen peroxide treatments given simultaneously show the same effect as either of them alone. Low levels of gamma and UV radiation exposures are also treated as stress in the present context. Studies show that irradiation of low-dose gamma rays results in enhanced excision repair of UV-induced pyrimidine dimers. However, in all the wild-type strains tested, none showed any effect on gamma rays response. The exposure to low doses of UV light did not show any effect on either the gamma rays or the UV response. It is suggested that the stress-induced enhancement of DNA repair can be of two types: 1) A general response to stress, which prepares the organism to survive in adverse circumstances (some of the proteins produced during this response also take part in the DNA repair), and 2) a particular response involving DNA damage, such as that caused by gamma irradiation. In this case, the DNA damage may act as a signal for enhancement of the DNA repair. PMID- 11215701 TI - Development of a novel plant system as biosensor for detecting environmental hazards and bioactive molecules through distinct responses. AB - Currently, chemicals are used excessively in medicine, industry, and agriculture throughout the world. Because of the current rise in environmental pollutants and hazardous exposures of human beings, there is an imperative need for monitoring the environment for biosafety. In addition, the importance of natural products with novel activity for drug or agrochemical scopes is being more and more realized. We report on a novel test system that can act as biosensors for detecting useful compounds while simultaneously monitoring or forecasting the biohazard exposure of organisms to chemicals as well as to physical factors in a given environment. Using different compounds and factors with known biological and cytotoxic activities, a detail plant test procedure has been developed that can be used in detecting and analyzing the value and/or danger of any given compound or treatment, including cell division inhibition, cytotoxicity, growth inhibition, and anticancer activities. The method provides a highly efficient single biosensor system that can replace several individual biotesting procedures. This plant assay procedure is a highly sensitive system for monitoring physical stress factors in the environment, including ionizing and nonionizing radiation. The procedure can be followed throughout the year because of the rapid growth rate of the plant used and its regeneration in ambient conditions. Therefore, the described system is highly useful to thoroughly monitor the environment and detection of new chemicals/compounds. PMID- 11215702 TI - A common regulator of cold and radiation response in Escherichia coli. AB - High levels of the protein product of gicA/cspE, a member of cspA family of cold stress genes, are known to be associated with several pleiotropic phenotypes in Escherichia coli. These include growth retardation in cold, suppression of rpsL31 mediated streptomycin resistance in cold, suppression of the chromosome partitioning mutation mukB, and cellular resistance to camphor. In this article, we demonstrate that the product of this gene is also involved in regulating UV and gamma radiation sensitivity. When present on a multicopy plasmid, gicA conferred UV sensitivity on those strains of E. coli K-12, in which it produces the cold-dependent growth retardation and streptomycin sensitivity but did not confer any gamma radiation sensitivity. A gicA::cat mutation, that inactivates the chromosomal gicA, made the cells highly sensitive to both UV and gamma radiation. These results indicate that the cellular level of GicA is quite critical in some aspects of DNA metabolism and suggest that this protein is a global regulator of multiple pathways affecting growth and translational fidelity in cold, DNA condensation, and chromosome partitioning during cell division. PMID- 11215703 TI - Molecular basis of UV-sensitive mutant strain MBH3 of Haemophilus influenzae Rd: identification of mutation in the uvrA gene. AB - We have previously reported on cloning a DNA repair gene designated as uvr3 by virtue of its ability to phenotypically complement the UV sensitivity of mutant strain MBH3. Subsequently, we identified the uvr3 gene to be the uvrA gene (gene identification number HI0249) of Haemophilus influenzae Rd. The uvrA gene is a component of the UvrABC excision repair pathway. We studied molecular basis of the UV sensitivity of the MBH3 strain and identified a G-->A transition at nucleotide position 2700 of the uvrA gene, altering the Trp-900 codon (TGG) to a nonsense codon (TGA). Thus, the UvrA protein produced in the mutant strain MBH3 is likely to be truncated and unable to carry out the UV-induced DNA repair, thereby rendering the strain UV sensitive. PMID- 11215704 TI - Expression of p53 and lactate dehydrogenase in murine fibrosarcoma following exposure to gamma-radiation. AB - Radiation-induced alterations in the levels of p53 and lactate dehydrogenase activities were studied in fibrosarcoma, following exposure to different doses of gamma-irradiation (2-10 Gy). The levels of p53 were elevated in the cytoplasm, while the lactate dehydrogenase activity in tumor tissue was considerably decreased. PMID- 11215705 TI - Effect of caffeine on the genotoxic effects of gamma radiation and 4-NQO in diploid yeast. AB - Caffeine is an environmental agent to which people are commonly exposed through medicines, drinks, food items, etc. It has been shown to be mutagenic in a number of test systems. In addition, it has also been shown to modify the mutagenic response of ionizing radiation, UV, and several chemical mutagens in a number of test systems. We have studied the effect of caffeine on gamma radiation and 4 Nitroquinoline 1-oxide (4-NQO)-induced gene conversion in the yeast Saccharomyces cerevisiae D7. Stationary phase cells were either exposed to 100-600 Gy of 60Co gamma radiation or treated with 0.15-0.3 microM 4-NQO (30 degrees C, 1 hour), after which they were plated on synthetic complete or minimal media with or without caffeine. Caffeine concentrations ranged from 5 to 15 mM. The results indicated that caffeine at 5 and 10 mM decreased gamma radiation-induced gene conversion frequencies significantly at 400 and 600 Gy. At 600 Gy, the decrease was about 30% and 50% with caffeine concentrations of 5 and 10 mM, respectively. In contrast, caffeine was found to increase the induced gene conversion frequency when cells treated with 0.15, 0.225, and 0.3 microM 4-NQO were plated on media containing caffeine. The increase with 5, 10, and 15 mM caffeine was approximately 1.5, 2, and 2.5, respectively, times the value of 4-NQO alone. The results indicate that the posttreatment repair processes following gamma irradiation or 4-NQO treatment are modified via different pathways. PMID- 11215706 TI - Retrospective dosimetry based on cytogenetic study of individuals chronically exposed to ionizing radiation. AB - Analysis of chromosomal aberrations (CAA) was carried out in 27 radiation workers with cumulative exposures of approximately 500 mSv received over a period of 2-3 decades. A similar study was carried out in 20 age- and gender-matched healthy individuals who served as controls. The average age of the exposed group was 50 years, and that of the controls was 51 years. The absorbed radiation dose was calculated by using the linear component of the in vitro dose response curve established for 60Co gamma-rays. In the controls we found only 3 dicentrics in 5,500 metaphases analyzed. In the exposed group, we detected 49 dicentrics and 1 centric ring in 13,900 metaphases analyzed. Because of the small number of dicentrics scored in each individual, the dose estimates of our method of study suffers from a large statistical uncertainty. The collective dose calculated from our data was 3.4 Sv. The difference in the physical dose based on personal monitoring and that from biological dosimetry may be attributed to the disappearance of lymphocytes carrying the aberrations from the living system. These results are consistent with the present knowledge of the kinetics of turnover of T-lymphocytes. Most residual damage appears to be from the long-lived component of T-lymphocytes with a mean life of 10 years. PMID- 11215707 TI - Combined effect of radiation and other agents: is there a synergism trap? AB - Most assessments of possible deleterious outcomes from environmental and occupational exposures concentrate on single agents and neglect the potential for combined effects--that is, synergisms or antagonisms. Biomechanistic considerations based on multistep processes, such as carcinogenesis, indicate the potential for highly detrimental interactions if two or more consecutive rate limiting steps are specifically effected by different agents. However, low specificity toward molecular structure or DNA sequence--and, therefore, exchangeability--of many genotoxic agents indicate little functional specificity and, hence, little vulnerability toward synergism in most occupational and environmental exposure situations. It is also evident that a low potential exists for the combined effects of common low-exposure situations wherein nongenotoxic agents with highly nonlinear dose-effect relationships and apparent thresholds are involved. A quantitative assessment of the contribution of synergistic interactions to the total detriment from natural and man-made toxicants based on experimental data is far away. There are important examples of combined exposures shown to lead to health effect risks that differ from those expected from simple addition-for example, the influence of smoking on radon- or asbestos-induced lung cancer and on ethanol-induced esophageal cancer. The existing data on combined effects is rudimentary, mainly descriptive, and rarely covers exposure ranges large enough to make direct inferences to present-day low-dose exposure situations. In view of the multitude of possible interactions among the large number of potentially harmful agents in the human environment, descriptive approaches will have to be supplemented by the use of mechanistic models for critical health endpoints, such as cancer. Finally, considering the shape of dose effect relationships for ionizing radiation, an important question arises from the unresolved question of whether real or apparent thresholds may be used for any genotoxic agent, separately or one time, for an exposed genome. PMID- 11215708 TI - Effects of turmeric on the activities of benzo(a)pyrene-induced cytochrome P-450 isozymes. AB - Turmeric and/or its main coloring component, curcumin (diferuloylmethane), have been shown to inhibit benzo(a)pyrene [B(a)P]-induced forestomach papillomas in mice. However, the mechanisms of turmeric-mediated chemoprevention are not well understood. To study the mechanisms of turmeric-mediated chemoprevention, we investigated the effects of turmeric feeding on the activities of isozymes of cytochrome P-450 (CYP450)--namely, ethoxyresorufin O-deethylase (EROD, CYP1A1) and methoxyresorufin O-demethylase (MROD, CYP1A2)--which are predominantly involved in the metabolism of B(a)P. We determined the activities of EROD and MROD by monitoring the formation of resorufin from respective substrates in the presence of microsomal proteins obtained from tissues of control, 1% turmeric, 1 mg B(a)P, and 1% turmeric + 1 mg B(a)P-fed Swiss mice. The results indicate that the administration of turmeric through diet significantly inhibited the activities of both EROD and MROD in forestomach (target organ), liver, and lung. In vitro studies employing curcumin, demethoxycurcumin, and bis-demethoxycurcumin suggest that curcumins are the inhibitors in turmeric. Inhibition of B(a)P metabolizing phase I enzymes (EROD, MROD) may be at least in part one of the possible modes of chemopreventive action of turmeric/curcumin. PMID- 11215709 TI - Low doses of heavy metals disrupt normal structure and function of rat platelets. AB - Aggregation, an important property of platelets, plays a key role in the coagulation of blood and is potentiated by ADP and adrenaline, whereas cAMP acts as a strong inhibitor. Because of the rise in the heavy metal load in the environment, more studies are necessary to look at its subtle effects in the animal system, wherein platelet structure and function can be targeted. We carried out structural analyses under phase contrast and scanning electronmicroscopy of the platelets prepared from 1/10 LD50 metal-treated rats. After mercury (Hg) and arsenic (As) treatment, the cell margins appeared irregular and wavy, with small pseudopodia-like protrusions from the surface. Cadmium (Cd) treatment caused loss of the general spindle shape, and the platelets assumed a round spongy appearance. All metal treatments effected enhanced collagen-induced aggregation and inhibited ADP- and arachidonic acid induced aggregation, whereas epinephrine accelerated aggregation in Hg and Cd treatment but inhibited aggregation in As treatment. Cd proved a potent inhibitor of phosphodiesterase, increasing the cAMP level in in vitro treatments at equimolar (5, 10, and 20 pmoles) concentrations. The rate of aggregation was enhanced with all the agonists used in in vitro Hg and As treatments, with concomitant reduction in cAMP, while Cd inhibited platelet aggregation. Thus, we can conclude that cytosolic cAMP, which is decreased by the metal-induced inhibition of phosphodiesterase, is a regulator molecule in platelet aggregation. Furthermore, it is also abundantly clear that equimolar doses of metals are not always equitoxic. Therefore, the action of each xenobiotic is not only due to the concentration used but also to the type of xenobiotic depending on its unique mechanism of action. PMID- 11215710 TI - Antimutagenic potential of extracts isolated from Terminalia arjuna. AB - Terminalia arjuna is an important medicinal plants widely used in the preparation of Ayurvedic formulations used against several ailments. The present investigation was aimed at the fractionation of crude extracts from the bark of T. arjuna in order to isolate and purify the antimutagenic factors present. The antimutagenicity assay was performed to check the modulatory effect of these fractions against NPD, sodium azide, and 2AF, using the Ames Salmonella his+ reversion assay. Most of the phenolic fractions exhibited mutagen specificity against direct-acting mutagens, being effective in suppressing the frameshift mutagen NPD but failing to inhibit sodium azide (base pair substitution)-induced his+ revertants. ET-1 fraction triterpenoid diglycoside showed a marked effect against sodium azide but was ineffective against NPD. In the case of the indirect acting mutagen 2AF, all the fractions were found to be quite potent in modulating its mutagenicity in both TA98 and TA100 tester strains of Salmonella typhimurium. The results indicate that the bark of T. arjuna harbors constituents with promising antimutagenic/anticarcinogenic potential that should be investigated further. PMID- 11215711 TI - Fetal magnetic resonance imaging. PMID- 11215712 TI - Magnetic resonance imaging of fetal thoracic abnormalities. AB - Fetal thoracic abnormalities are increasingly being detected using prenatal ultrasound. Prenatal magnetic resonance imaging is an important adjunct in evaluation of fetal chest lesions. It can help differentiate different masses and is most helpful in evaluation of large or atypical masses. It also is very important in planning in utero interventional procedures, delivery, and immediate postnatal surgery. PMID- 11215713 TI - Ultrasound versus magnetic resonance imaging in fetal evaluation. AB - Ultrasound is the screening modality of choice for fetal imaging. However, there are circumstances in which an alternate imaging modality is needed for additional information regarding fetal anatomy or pathology. Fast magnetic resonance imaging (MRI) is increasingly being used as a correlative imaging modality in pregnancy because it uses no ionizing radiation, provides excellent soft-tissue contrast, and has multiple planes for reconstruction and a large field of view. However, sonographic evaluation of the fetus still is important to select the appropriate fetuses for magnetic resonance (MR) examination and to guide the protocol of the examination. Performance of high-quality sonographic and MR examinations as well as interpretation by individuals familiar with prenatal diagnosis are important factors for optimal parental counseling. MRI frequently adds additional information beyond that available with ultrasound. This information commonly changes patient counseling and, at times, patient management. PMID- 11215714 TI - Normal fetal anatomy as visualized with fast magnetic resonance imaging. AB - The development of ultrafast sequences has revolutionized fetal magnetic imaging (MRI). Fetal anatomy can be characterize precisely by MRI. This is particularly true for evaluation of the central nervous system, for which magnetic resonance (MR) evaluation is superior to ultrasound evaluation. MR allows analysis of development of the cerebrum as well as posterior fossa structures. Awareness of the normal sequence of maturation as well as the approximate timing of development of key structures is useful for evaluating the developing fetus. MRI also permits evaluation of the oropharynx, lungs, diaphragm, and intra-abdominal and retroperitoneal structures. Occasionally, beautiful depiction of smaller structures, including extremities and details of the face and neck may be obtained, but this is dependent on the orientation of the fetus and the plane of imaging as well as the section thickness. MRI is useful in assignment of fetal gender as well as in evaluation of the chorionicity of twin gestations. This report illustrates the normal appearance of the developing fetus as seen on fast sequences during the second and third trimesters. PMID- 11215715 TI - Role of magnetic resonance imaging in fetal surgery. AB - Prenatal magnetic resonance imaging (MRI) has several advantages over obstetric ultrasound, including a larger field of view, superior soft-tissue contrast, more precise volumetric measurements, and greater accuracy in the demonstration of intracranial abnormalities. Prenatal MRI has been shown to positively and incrementally influence management in a substantial proportion of patients being considered for fetal intervention. Despite these findings, precise indications for prenatal MRI in the setting of fetal surgery are not yet established, because both prenatal MRI and fetal surgery are relatively new techniques that remain in evolution. Conditions in which prenatal MRI appears to contribute to fetal surgical planning and postoperative evaluation are described in this review. These conditions include congenital diaphragmatic hernia, cystic adenomatoid malformation, sacrococcygeal teratoma, complicated twin pregnancies, upper airway obstruction, and myelomeningocele. PMID- 11215716 TI - Fetal and placental volumetric and functional analysis using echo-planar imaging. AB - Recent and past work using echo-planar imaging (EPI) in pregnancy has allowed important anatomic and physiological information to be obtained, giving advantages over conventional radiological methods such as ultrasound. EPI is a quick, convenient method of measuring organ volumes. The volumetric estimates throughout gestation correlate well with known fetal weight at these gestations. Relaxation time measurements also can be made in the placenta and lungs. By combining the changes in relaxation and volume with gestation in the future, it may be possible to develop an "index of maturity." This could be used to accurately reflect lung maturation. T1 and T2 parameters in the placenta decreased with gestational age and with abnormal placentation. EPI can be used to assess perfusion in the placenta and flow in the uterine arteries because of its rapid acquisition times. These techniques have been applied to assess perfusion within the fetal brain. PMID- 11215717 TI - Fast fetal magnetic resonance imaging techniques. AB - New hardware and software allow for increased magnetic resonance imaging (MRI) speed. This speed is crucial for MRI of the fetus, where motion degrades image quality. Single-shot sequences such as echo-planar and single-shot fast spin echo now are practical with most clinical scanners. This article reviews and illustrates the physics of fast magnetic resonance sequences. PMID- 11215718 TI - Update: outbreak of acute febrile illness among athletes participating in Eco Challenge-Sabah 2000--Borneo, Malaysia, 2000. AB - During September 7-11, 2000, CDC was notified by the Idaho Department of Health, the Los Angeles County Department of Health Services, and the GeoSentinel Global Surveillance Network of at least 20 cases of acute febrile illness in three countries; all ill patients had participated in the Eco-Challenge-Sabah 2000 multisport expedition race in Borneo, Malaysia, during August 21-September 3, 2000. Participants included athletes from 29 U.S. states and 26 countries. This report updates the ongoing investigation of this outbreak through December 2, which suggests that Leptospira were the cause of illness and that water from the Segama River was the primary source of infection. Participants in adventure sports and exotic tourism should be aware of potential exposure to unusual and emerging infectious agents. PMID- 11215719 TI - Health-related quality of life among persons with epilepsy--Texas, 1998. AB - Epilepsy is a central nervous system disorder characterized by unprovoked, recurrent seizures that may affect physical, mental, or behavioral functioning. In 1995, approximately 2.3 million persons residing in the United States had epilepsy. Approximately 181,000 new cases of epilepsy are diagnosed each year, with annual estimated costs of $12.5 billion in medical care and lost productivity. Because epilepsy has a substantial impact on health (e.g., physical and psychosocial difficulties, side effects of anticonvulsant therapy, lifestyle restrictions, and perceived stigmatization), self-reported physical and mental health-related quality of life (HRQOL) measures are useful in gauging the impact of epilepsy on persons with the disorder. Persons with chronic health disorders are at risk for impaired HRQOL. Few studies have examined the HRQOL of persons with epilepsy, and none has used a representative sample of adults residing in the United States. This report examines data from the 1998 Texas Behavioral Risk Factor Surveillance System (BRFSS) that included a question about epilepsy; findings indicate that persons with epilepsy reported substantially worse HRQOL than persons without epilepsy. Community-based interventions such as the Sepulveda Epilepsy Education Program that address medication self-management, psychosocial self-management, and other education interventions can improve the quality of life for persons with epilepsy. PMID- 11215720 TI - Nongranulomatous chronic idiopathic enterocolitis: a primary histologically defined disease. AB - Nongranulomatous chronic idiopathic enterocolitis is characterized by sudden onset of severe watery diarrhea, malabsorption, exudative enteropathy, frequent appearance of shallow ulcerations, and variable degrees of villus atrophy. In the absence of infectious and pharmacologic causes, the presence of a predominantly acute inflammatory infiltrate limited to the lamina propria establishes the diagnosis. No underlying disease appears during prolonged follow-up. The etiology remains unknown. The disease is generally corticosteroid-responsive; low-dose maintenance therapy is frequently required. The long-term prognosis is guarded. Three of 11 patients died of opportunistic infections or resistance to therapy. PMID- 11215721 TI - Low endogenous prostaglandin E2 predisposes to relapsing inflammation in experimental rat enterocolitis. AB - Intramural injection of peptidoglycan-polysaccharide (PG-PS) induces acute enterocolitis that spontaneously relapses in Lewis but not Fischer rats. Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) induce prostaglandin E2 (PGE2) secretion, which inhibits secretion of these cytokines by macrophages, suggesting an inhibitory feedback mechanism. We postulate that Lewis rat susceptibility to relapse is due to an imbalance between protective prostaglandins and cytokines. Female Fischer and Lewis rats were injected with PG PS (37.5 microg/g) or human serum albumin intramurally. Tissue IL-1alpha and PGE2 immunoreactivities and myeloperoxidase (MPO) activity were determined. Relapsing rats had lower PGE2 and PGE2/IL-1alpha ratios than nonrelapsing rats (P < 0.05). In Fischer rats, 2 mg/kg/day of indomethacin potentiated cecal MPO and IL-1alpha concentrations above PG-PS alone (P < 0.05). Misoprostol treatment blocked PG-PS induced IL-1alpha and MPO and inhibited the potentiating effect of indomethacin on MPO and IL-1alpha (P < 0.05). In conclusion, increased endogenous PG may be protective against relapsing inflammation in PG-PS induced enterocolitis, at least partially via inhibition of proinflammatory cytokines. Imbalance between protective prostaglandins and proinflammatory cytokines may be involved in the pathogenesis of chronic relapsing inflammation in genetically susceptible hosts. PMID- 11215722 TI - Somatostatin and octreotide stimulate short-circuit current in human colonic epithelium. AB - In vitro somatostatin is a potent inhibitor of intestinal ion secretion in animal models and cultured human cell lines, providing a rationale for its use in secretory diarrheas. However, the effects of somatostatin on ion transport in native human colonic epithelium have not been reported. In this study the effects of somatostatin and octreotide on the basal short-circuit current and the cAMP- and Ca2+-stimulated short-circuit current were studied in isolated human colonic mucosa mounted in Ussing chambers. Under basal conditions somatostatin and octreotide (1 micromol/liter) stimulated a small, bumetanide-sensitive increase in short-circuit current. Following stimulation of secretion with prostaglandin E2, somatostatin and octreotide further increased the short-circuit current in a dose dependent fashion (ED50 approximately 10 nmol/liter for both). This stimulation of short-circuit current was not affected by pretreatment of the tissue with basolateral tetrodotoxin (1 micromol/liter) or mucosal amiloride (10 micromol/liter). In contrast, somatostatin and octreotide had no effect when secretion was stimulated with 8-bromo-cAMP, and pretreatment of the tissue with somatostatin and octreotide (0.1 micromol/liter) did not alter the secretory response to carbachol. The absence of any inhibitory effect of somatostatin and octreotide on electrogenic secretion in the human colon may explain the variable results obtained when somatostatin or octreotide are used for the treatment of secretory diarrheas. PMID- 11215723 TI - Oxygen diffusive barriers of rat distal colon: role of subepithelial tissue, mucosa, and mucus gel layer. AB - The contributions of subepithelial tissue, mucosa, and mucus gel layer as restraints for oxygen diffusion in rat distal colon in vitro were assessed by comparing oxygen transfer through preparations of isolated submucosa, isolated mucosa with and without the superficial mucus gel layer, and mucosa-submucosa mounted as flat sheets in a diffusion chamber. One side of the chamber was gassed with 95% O2-5% CO2 while the time course of oxygen concentration rise was measured in the continuously stirred opposite side, initially equilibrated with near-zero oxygen solution. The procedure does not affect epithelial viability. Diffusion in isolated mucosa was the same before and after KCN (5 mM) treatment, suggesting that epithelial oxygen consumption does not influence transfer rates. Subepithelial tissue, mucosa, and mucus gel layer are roughly responsible, respectively, for 12%, 56%, and 32% of oxygen diffusive hindrance. Diffusion coefficients range from 13% (mucosa-submucosa) to 54% (isolated submucosa) of that of water. Subepithelial tissue accounts for about 12% of total diffusive restraint. PMID- 11215724 TI - Induction of enlarged intestinal lymphoid aggregates during acute glutathione depletion in a murine model. AB - Glutathione is a nonenzymatic antioxidant synthesized by most animal cells and is depleted in inflammatory bowel disease. The effects of glutathione depletion on intestinal histology and inhibitory neurochemicals was examined in a mouse model. Glutathione depletion in A/J mice involved inhibition of gamma-glutamylcysteine synthetase using L-buthionine-(S,R)-sulfoximine (BSO) for 10 days. Ileum and colon were obtained from saline-control mice, BSO-treated mice, and BSO-treated mice receiving ascorbate or glutathione monoethylester. Glutathione, lipid peroxides, and nicotineamide adenine dinucleotide phosphate diaphorase activity were measured by colorimetric assays. Vasoactive intestinal peptide was measured by radioimmunoassay. Glutathione depletion induced enlargement of mucosal submucosal lymphoid aggregates without germinal centers in ileum and colon. These aggregates were prevented by supplementation with glutathione monoethylester but not ascorbate. Tissue levels of inhibitory neurochemicals were unchanged. Depletion of glutathione appears to induce enlarged lymphoid aggregates by recruitment of lymphocytes from the peripheral circulation. A component of the inflammation that develops in inflammatory bowel disease could be related to depletion of tissue levels of glutathione. PMID- 11215725 TI - Noninvasive in vivo analysis of human small intestinal paracellular absorption: regulation by Na+-glucose cotransport. AB - Activation of intestinal Na+-glucose cotransport increases paracellular movement of inert tracers in cultured monolayers, isolated rodent intestinal mucosae, and in rodents in vivo. However, not all studies have demonstrated comparable effects on human intestinal paracellular absorption. We sought to assess the effects of Na+-glucose cotransport on paracellular absorption in human beings using a simple noninvasive assay. Study subjects drank six 200-ml doses of test solution, composed of 0.8% w/v creatinine (sufficient to overwhelm endogenous creatinine) in 277 mM glucose or mannitol and urine was collected. Intestinal creatinine absorption is paracellular. Once absorbed, creatinine is cleared into the urine. Therefore, urinary creatinine recovery reflects intestinal paracellular creatinine absorption. Total urinary creatinine recovery was 55% +/- 4% of creatinine ingested with glucose and 38% +/- 9% of creatinine ingested with mannitol (p < 0.001). Thus, intestinal paracellular absorption of creatinine is increased by the presence of luminal glucose. Our results are consistent with in vivo human regulation of mucosal permeability by Na+-glucose cotransport. PMID- 11215726 TI - Insecure attachment in a subgroup with ulcerative colitis defined by ANCA status. AB - This study is the first test of the novel hypothesis that perinuclear anti neutrophil cytoplasmic antibody (p-ANCA) marks an etiological division between stress-susceptible and stress-neutral ulcerative colitis. Subjects were 47 UC patients with known p-ANCA status (19 p-ANCA-positive, 28 p-ANCA-absent). Controls were 77 university students. Subjects and controls completed the Reciprocal Attachment Questionnaire. Subjects were categorized as avoidant/nonavoidant and anxious/nonanxious based on scores for compulsive self reliance and compulsive care seeking, respectively. A higher prevalence of avoidant attachment was present in p-ANCA-absent (58.6%) than p-ANCA-positive subjects (22.2%, chi-square = 5.95, P < 0.02). There was no difference in the prevalence of anxious attachment between p-ANCA-absent and p-ANCA-positive subjects. There was no difference in clinical and psychiatric variables between groups. This finding provides support for a psychobiological contribution to UC in a subgroup identified by the absence of p-ANCA. PMID- 11215727 TI - Histoplasmosis capsulatum as a cause of lower gastrointestinal bleeding in common variable immunodeficiency. AB - Infection with Histoplasma capsulatum is the most common systemic fungal infection in the United States, but symptomatic gastrointestinal disease is rare. Gastrointestinal involvement is seen in patients with an established immunosuppressed state that predates any infection. We report a patient presenting with gastrointestinal bleeding ultimately diagnosed with disseminated histoplasmosis. Work-up led to the diagnosis of common variable immunodeficiency, a diagnosis not previously described as associated with gastrointestinal histoplasmosis. Resolution of the colonic ulcer was documented after appropriate antifungal therapy, underscoring the importance of including this infectious process in the differential of a patient without other risk factors for colonic ulceration. PMID- 11215728 TI - Response by Dr. Allen. Anal canal resting tone. PMID- 11215729 TI - Misinterpretation of human electrogastrograms related to inappropriate data conditioning and acquisition using digital computers. AB - Despite the fact that digital techniques for data acquisition and processing were widely used in electrogastrographic (EGG) research during the last decade, inappropriate signal conditioning and digitization are still potential pitfalls threatening the reliability of the experiments. The aim of this paper was to review: (1) the importance of the antialiasing low-pass filtering for reducing recording artifacts and interferences, (2) the advantages brought by the proper choice of filter cutoff frequency and the slope for the decrement of the minimal required sampling frequency, (3) the impact of incorrectly selected sampling frequency on data interpretations, with particular attention to the percent distribution ranges, and (4) the "leakage effect" related to the finite number of samples processed simultaneously in frequency domain representation of the recordings. A model of electrogastrographic (EGG) recording was mixed with a model of electrocardiographic (ECG) artifact. The resulting finite-duration signal was low-pass filtered and then digitized with a sampling frequency of 1 Hz. The cutoff frequency of the first-order low-pass filter was altered from 0.5 to 0.1 Hz. Amplitude frequency spectra of the digitized recordings were investigated. An example with a real human electrogastrogram in which an ECG artifact was present confirmed the simulation results. When a first-order anti aliasing filter is utilized at least a fivefold difference between the filter cutoff frequency and the sampling frequency is recommended for compliance with the Nyquist theorem of digitization. Leakage effects associated with the finite time duration of the recordings and the use of the discrete Fourier transform should be considered when frequency domain analysis is performed. Misinterpretation of the "bradygastric" and "tachygastric" ranges in the percent distribution of EGG frequency components is possible if inappropriate signal conditioning and digitization are employed. PMID- 11215730 TI - Abnormally rapid gastric emptying of an isosmotic liquid meal in patients with megaduodenum. AB - Duodenal resistance to gastric outflow is known to participate in the regulation of gastric emptying of liquids in animals, but the role of this mechanism in humans has not been extensively investigated. In this work we studied the gastric emptying of liquids in patients with megaduodenum, who putatively have increased duodenal receptivity to gastroduodenal transfer of liquids. Subjects included eight patients with megaduodenum and eight healthy volunteers. Since megaduodenum in all cases was associated with Chagas' disease, a further reference group consisting of 11 chagasic patients without megaduodenum was also studied. Fasted subjects ingested 200 ml of an isotonic dextrose solution labeled with 15 MBq of technetium-99m coupled to sulfur colloid, as an unabsorbable marker. Images of the anterior aspect of the stomach were taken immediately after test meal ingestion and thereafter up to 1 hr. Decay-corrected counts over the gastric region along time yield the calculation of early (5 min) and late (60 min) gastric retention as well as gastric emptying half-times (T1/2). Early gastric retention in patients with megaduodenum (median; range: 48%; 18-64%) was significantly lower (P < 0.05) than in both patients without megaduodenum (59%; 40-86%) and controls (82%; 68-99%). T1/2 values in patients with megaduodenum (5 min; 3-17 min) were also significantly lower (P < 0.01) than in patients without megaduodenum (23 min; 4 to >60 min) and controls (29 min; 13-60 min). There were no significant differences between the three groups concerning late gastric retention. We conclude that the early phase of gastric emptying of liquids is abnormally accelerated in patients with megaduodenum, which suggests that increased duodenal receptivity may have a significant effect on the gastroduodenal transfer of liquids in humans. PMID- 11215731 TI - Abnormal propagation pattern of duodenal pressure waves in the irritable bowel syndrome (IBS) [correction of (IBD)]. AB - The propagation pattern of individual pressure waves in the gastroduodenal area in IBS is unexplored. We performed antroduodenojejunal manometry on 26 patients with IBS--13 with diarrhea predominant IBS (IBS-D) and 13 with constipation predominant IBS (IBS-C)--and 32 healthy controls. Neuropathic-like motor abnormalities were found in 38% of the patients with conventional manometric evaluation. With high-resolution analysis additional abnormalities were observed in the majority of the patients, with increased frequency of retrograde pressure waves postprandially in both IBS subgroups and in phase II in IBS-D. A correlation between subjective gastrointestinal symptoms and the frequency of retrograde pressure waves in phase II in IBS-D was demonstrated. Motility indices and the number of long clusters were also higher in patients compared to controls. To conclude, an abnormal propagation pattern of individual duodenal pressure waves in IBS patients was demonstrated and found to be related to symptom severity in diarrhea-predominant IBS. High-resolution analysis adds information to standard manometry. PMID- 11215732 TI - Helicobacter pylori in the oral cavity: high prevalence and great DNA diversity. AB - To test the hypothesis that Helicobacter pylori may be transmitted by the oral oral route, we applied nested PCR and DNA sequencing to detect and analyze H. pylori DNA in the oral cavity of 20 adult patients undergoing endoscopy. Dental plaques of molars, premolars, and incisors and saliva were collected. Additional paraffin-embedded gastric biopsies were analyzed in four patients. Two sets of highly sensitive and specific primers, EHC-U/EHC-L and ET5-U/ET-5L directed to a 860-bp fragment of H. pylori DNA, were used in the nested PCR. Eight patients had an active infection in the stomach determined with the [13C]urea breath test and the other 12 were negative. Nested PCR showed that all 20 subjects (100%) were positive for H. pylori in the oral cavity. DNA sequencing demonstrated that all tested PCR products of the expected size from the oral samples have more than 97% identity with that from H. pylori type strain ATCC 43629. However, sequences differed in oral samples from different subjects as well as between different oral locations and gastric biopsies within the same individuals. In conclusion, the oral cavity may be a permanent reservoir for H. pylori and can harbor multiple H. pylori strains at the same time. PMID- 11215733 TI - Isotope ratio mass spectrometry (IRMS) versus laser-assisted ratio analyzer (LARA): a comparative study using two doses of. AB - This study was carried out to compare the measurements and the diagnostic accuracy of the traditional expensive IRMS and the new economical LARA system using two doses of [13C]urea + two different test meals in patients undergoing upper gastrointestinal endoscopy, both before and after anti-Helicobacter treatment. A total of 354 dyspeptic patients underwent endoscopy with gastric biopsies to diagnose H. pylori infection by CLO-test and histology. No patients had taken antibiotics, bismuth, or antisecretory drugs in the 4 weeks before testing. After overnight fasting, breath samples were collected simultaneously in both plastic and glass tubes at baseline and at 30 and 60 min after urea ingestion. In 237 patients 100 mg [13C]urea + Ensure and in 117 patients 75 mg [13C]urea + citric acid were given. The test was also performed with the two urea dosages and meals in 67 and 64 infected patients, respectively, four weeks after anti-Helicobacter therapy. H. pylori was considered eradicated when both biopsy based tests were negative. A delta value >5 per thousand was considered positive. Breath samples with insufficient CO2 levels at both 30 and 60 min were excluded from final analysis (N = 37 in pre- and N = 8 in posttreatment). There was excellent agreement between overall delta values of the two machines with both [13C]urea 100 mg + Ensure and [13C]urea 75 mg + citric acid. The 95% CI of the difference against the mean was wider with the former (mean -1.3, +6.3, and -9.4) than with the latter urea dosage and test meal (mean -1.2, +5.2 and -8.1). LARA and IRMS were equally effective (P = NS) in distinguishing infected from uninfected patients before therapy using both doses of [13C]urea and test meals (sensitivity ranged from 95% to 99% and specificity from 95% to 97%). This good performance was maintained in the posttreatment phase (sensitivity ranged from 90% to 100% and specificity from 90% to 97%), without any statistical difference among the various combinations (P = NS). The LARA system is a valid alternative to IRMS in the diagnosis of H. pylori infection. Both machines provide highly reliable results after 30 min, so that the 60 min sample can be avoided. The dose of 75 mg + citric acid suffices to ensure an accurate UBT. The test performed with both devices and [13C]urea dosages is very effective also for posttherapy evaluation of H. pylori status. PMID- 11215735 TI - Ambulatory pH monitoring: how to truly test the patient? PMID- 11215734 TI - Role of mucus reduction and luminal acid elevation in increased susceptibility of stomach to nonsteroidal antiinflammatory drug-induced injury in arthritic rats. AB - We investigated the role of gastric mucus and acid secretion in the increase of nonsteroidal antiinflammatory drug-induced gastric lesions in adjuvant-induced arthritic rats. Both aspirin- and indomethacin-induced gastric injury were remarkably worsened in the arthritic rats. In the arthritic rats, the amounts of mucus glycoprotein in both the mucosa and adherent gel layer were respectively decreased to 70% and 34% of those in normal rats, while gastric acid secretion was augmented to 1.5-fold. The gastroprotective antiulcer agent ecabet sodium, which increased the mucus content in the gel layer but did not affect the luminal acid contents, prevented the increase of both lesions induced by aspirin and indomethacin. Cimetidine also inhibited the formation of aspirin- and indomethacin-induced damage as well as the acid secretion in the arthritic rats. In conclusion, an imbalance between gastric defensive and aggressive systems due to the loss of adherent mucus glycoprotein and the elevation of the luminal acid contents seems to account for the increased susceptibility of the lesion-inducing properties of nonsteroidal antiinflammatory drugs in arthritic rats. PMID- 11215736 TI - Enterococcal bactibilia in patients with malignant biliary obstruction. AB - Biliary obstruction due to pancreaticobiliary malignancy is often accompanied by bactibilia. The aims of this study were to clarify the impact of preoperative antibiotic use on bile bacterial flora and to identify the bile bacteria responsible for postoperative septic complications in patients with malignant biliary obstruction. Eighty-four patients with malignant biliary obstruction underwent a biliary decompression procedure before definitive surgery. In 63 patients (75%), preoperative bile culture was positive, with nine species being detected. Only the incidence of enterococcal bactibilia increased after antibiotic use (P = 0.0009), with a 16% incidence before and 63% after antibiotic use. When analyzing the correlation between preoperative bile bacteria and postoperative complications, only the Enterococcus species was associated with the occurrence of complications (P = 0.037). In conclusion, bile bacterial flora changes after preoperative antibiotic use, with a significant increase in the incidence of enterococcal bactibilia. The Enterococcus species is most responsible for postoperative septic complications in patients with malignant biliary obstruction. PMID- 11215738 TI - Immunochemical fecal occult blood test is inadequate for screening test of stomach cancer. AB - The present study was carried out to investigate the diagnostic accuracy of the immunochemical fecal occult blood test in the screening for stomach cancer. In the hospital-based case-control study, the test was positive in 6 (14.3%) subjects with stomach cancer, in 32 (76.2%) subjects with colorectal cancer, and in 10 (7.9%) healthy subjects, respectively, showing a significant difference in detection rate between the subjects with stomach cancer and colorectal cancer (p < 0.01). In the population-based cross-sectional study, detection rate for stomach cancer was 0.13% and 0.15% for negative and positive groups decided by immunochemical fecal occult blood test, indicating no significant difference. These results reveal that the immunochemical fecal occult blood test is inadequate as the screening test for stomach cancer and suggest that examination of the upper digestive tract is unnecessary in cases where the result of fecal occult blood test is positive with no sign of colorectal diseases. PMID- 11215737 TI - No major difference in K-ras and p53 abnormalities in sporadic and hereditary nonpolyposis colorectal adenomas. AB - K-ras and p53 gene mutations are known to occur in high frequencies in sporadic colorectal cancers, but findings are inconsistent in hereditary nonpolyposis colorectal cancer (HNPCC). We compared K-ras codon 12 and 13 gene mutations and p53 protein overexpression in 48 HNPCC (positive for Amsterdam criteria) and 59 sporadic colorectal adenomas, to examine whether they may represent similar or different molecular pathways to cancer. In sporadic adenomas K-ras mutations were detected in 32% and p53 overexpression in 31% of the cases. Similarly, K-ras mutations and p53 overexpression were both found in 25% of HNPCC adenomas. The frequencies of these abnormalities were not significantly different between HNPCC and sporadic adenomas. When taking differences in adenoma size into account, the frequencies were even more similar. In conclusion, these results suggest a similar molecular pathway to adenomas in HNPCC and sporadic carcinogenesis, with respect to involvement of K-ras and p53. PMID- 11215739 TI - Mutations at vicinity of catalytic sites of hepatitis C virus NS3 serine protease gene isolated from hepatocellular carcinoma tissue. AB - The mechanism of hepatitis C virus (HCV) -induced hepatotocellular carcinoma (HCC) is still unknown, but in vitro studies clearly suggest that HCV proteins exert a direct effect on liver carcinogenesis. HCV NS3 serine protease is known to play a key role in the life cycle of the virus and may interact with the host cellular regulatory proteins. The aim of the present study was to conduct a genetic analysis of the HCV NS3 gene coding for the serine protease isolated from serum, tumor, and nontumor tissue of HCC patients. RNA was extracted and HCV cDNA was amplified by nested reverse transcriptase-polymerase chain reaction (RT-PCR). Sequence comparison yielded unique changes at the vicinity of the catalytic sites of the NS3 clones isolated only from HCC tissue. These changes included the insertion of a "large" and charged amino acid, substitution of a polar with a hydrophobic amino acid, and substitution of a charged with a polar amino acid. Those changes affect the electrostatic charge around the active site, and thus the activity and substrate specificity of the serine protease. This is the first study to define significant amino acid changes at the catalytic domain of the NS3 serine protease gene isolated from HCC tissue. PMID- 11215740 TI - Hepatocellular carcinoma associated with adult-type citrullinemia. PMID- 11215741 TI - Early mutation of precore (A1896) region prior to core promoter region mutation leads to decrease of HBV replication and remission of hepatic inflammation. AB - To evaluate the relationship between mutations and clinical courses, we investigated precore (preC) and core promoter (CP) mutations and serum HBV DNA levels in HBe-antibody-positive HBV carriers. Fifty-six asymptomatic carriers (ASC), 29 patients with chronic hepatitis who showed normal ALT levels for more than two years (CH-ASC), 31 patients with chronic hepatitis (CH), and 32 patients with hepatocellular carcinoma (HCC) were studied. Almost all patients (99.2%) had mutations in either CP or preC. Mutation only in preC (A1896) was present in 52.2% with ASC, 25.0% with CH-ASC, 16.1% with CH, and 8.0% with HCC, and was significantly higher in ASC (P < 0.01). The patients with only preC mutation showed low HBV DNA levels in each clinical stage. The mutation of preC (A1896) prior to the mutation of CP might control the replication of HBV, which leads to the remission of hepatitis. PMID- 11215742 TI - Seroepidemiology of TT virus infection and relationship between genotype and liver damage. AB - TT virus (TTV) has been identified in patients with posttransfusion hepatitis of unknown etiology and is thought to be a new hepatitis virus. We determined the extent of TTV infection in the Japanese general population and the relationship between TTV DNA genotype and liver damage. In 1998, we tested 847 serum samples for TTV. TTV DNA was assayed by a nested polymerase chain reaction and classified into three different genotypes and eight subtypes. TTV DNA was detected in 25.3% and 32.4% of the inhabitants of the two areas studied, respectively. The genotype distribution was similar in both areas. G1, G2, and G3 were 60%, 20%, and 5%, respectively. Of the 20 subjects with TTV DNA alone and elevated serum ALT levels, 18 were G1, one was G2, and one was G3. TTV infection is endemic in the Japanese general population studied. The main TTV genotype, G1, may be related to the ensuing liver damage. PMID- 11215743 TI - Liver damage in hemodialysis patients with hepatitis C virus viremia: a prospective 10-year study. AB - Hepatitis C virus (HCV) infection is a major problem associated with hemodialysis. The extent of liver damage in hemodialysis patients with chronic HCV infection has not been thoroughly documented. The aim of this study was to evaluate liver damage of hemodialysis patients infected with HCV. A total of 233 hemodialysis patients were categorized into two groups at entry: group X, 80 positive for serum HCV RNA, and group Y, 153 negative for serum HCV RNA. All were tested for serum alanine aminotransferase (ALT) serially from 1989 to 1998, and serum hyaluronic acid (HA), serum type-IV collagen (IV-C), platelet counts, and ultrasonographic examination of the liver was done in 1998. In group X, 61.3% had continuously abnormal ALT levels for over six months followed by normal ALT levels. Of the group X patients, 11.3% had abnormal ALT levels in 1998, and in three, hepatocellular carcinoma occurred. Mean HA and IV-C levels in group X (648.8 and 188.7 ng/ml, respectively) were significantly higher than in group Y (213.1 and 165.5 ng/ml, respectively) (P < 0.05). Ultrasonographic findings significantly correlated with serum HA level and platelet counts and showed significantly more abnormalities in group X than in group Y (P < 0.05). From these findings, a combined examination with ultrasonography and serum fibrogenesis markers is useful for detection of liver damage in hemodialysis patients with HCV viremia. PMID- 11215744 TI - Correlation of high levels of hyaluronan and cytokines (IL-1beta, IL-6, and TGF beta) in ascitic fluid of cirrhotic patients. AB - Our objective was to investigate the relationship between endotoxin and hyaluronan synthesis and release in serum and ascitic fluid from cirrhotic patients. We studied hyaluronan, endotoxin, albumin, and creatinine levels in ascitic fluid and plasma and cytokine levels (IL-1beta, IL-6, TGF-beta) in ascitic fluid. TGF-beta, IL-6, and IL-1beta correlation analyses indicated a strong dependence of the production of these cytokines on endotoxin levels. Correlation analyses for TGF-beta and IL-6 indicated a strong dependence of the production of hyaluronan on cytokine levels and, to a lesser extent, on IL-1beta levels. Hyaluronan analysis indicated that a certain glycosaminoglycan level is required in ascites before its appearance in plasma. Our results disclosed elevated plasma hyaluronan concentrations. The simultaneous increased hyaluronan levels in ascitic fluid do not seem to be derived from the systemic circulation. In conclusion, the high hyaluronan-ascites/hyaluronan-plasma ratio suggests an intrinsic hyaluronan production from peritoneal cells induced by endotoxins. PMID- 11215746 TI - Paroxysmal nocturnal hemoglobinuria with no evidence of hemolysis presenting as Budd-Chiari syndrome. PMID- 11215745 TI - Parameters of microsomal and cytosolic liver function but not of liver perfusion predict portal vein velocity in noncirrhotic patients with chronic hepatitis C. AB - Our aim was to compare color-coded Doppler sonography (CCDS) and quantitative testing of liver function (QTLF) in patients with chronic hepatitis C. In all, 74 patients with chronic hepatitis C and mild fibrosis underwent QTLF, which included aminopyrine breath test (ABT), galactose elimination capacity (GEC), sorbitol clearance (SC), and indocyanine green clearance (ICG). Hepatic artery velocity and resistance index (HA-V, HA-RI) as well as portal vein velocity (PV V) were measured by CCDS. ABT, GEC, and PV-V were significantly reduced, whereas SC1, ICG, HA-V, and HA-RI showed normal levels. There was a significant correlation between reduction in PV-V only with GEC and ABT. QTLF did not correlate with HA-V and HA-RI. In conclusion, in hepatitis C patients with liver fibrosis, ABT and GEC are decreased significantly, which was paralleled by a reduction of PV-V. Unexpectedly SC1 and ICG, the classical hepatic perfusion parameters, do not correlate with the parameters measured by CCDS. PMID- 11215748 TI - Octreotide treatment in patients with severe acute pancreatitis. AB - We investigated the effect of octreotide in the treatment of severe acute pancreatitis in a case-control study. Experimental and clinical studies on the effect of octreotide in the treatment of acute pancreatitis have shown controversial results. Since January 1992, we have been conducting a prospective randomized study on the effect of octreotide in severe acute pancreatitis, in three hospitals in Israel. The entering criteria included three or more of the Ranson prognostic signs and CT findings of severe pancreatitis. Patients were randomly assigned to conservative treatment either with or without octreotide (0.1 mg subcutaneously three times a day). The end points of the study included: complication rate (ARDS, sepsis, renal failure, pseudocyst, fistula, and abscess), length of hospital stay, and mortality. From January 1992 to December 1996, 60 patients entered the study. After evaluating the files, 10 patients were excluded due to failure to meet the entering criteria, incomplete data, or incorrect diagnosis. Of the remaining 50 patients, 25 were assigned to octreotide (treatment group) and 25 to conservative treatment only (control group). The two groups matched with regard to age, sex, etiology, and severity of the disease. The complication rate was lower in the treatment group with regard to sepsis (24% vs 76%, P = 0.0002) and ARDS (28% vs 56%, P = 0.04). The hospital stay was shorter in the treatment group (20.6 vs 33.1 days, P = 0.04). Two patients died in the treatment group and eight in the control group (P < 0.019). These results suggest that octreotide may have a beneficial effect in the treatment of severe acute pancreatitis. PMID- 11215747 TI - Ki-1 lymphoma with nodular involvement in liver and spleen: possible role of cytokines in systemic manifestation of fever and leukocytosis. PMID- 11215749 TI - Heat shock response is associated with protection against acute interstitial pancreatitis in rats. AB - We recently reported that hyperthermia induces pancreatic expression of heat shock proteins (HSPs), particularly HSP70 isoforms, and protects against cerulein pancreatitis. We have now studied whether a double hyperthermia amplifies these effects and whether hyperthermia also protects against dibutyltin dichloride (DBTC)-induced pancreatitis. A further aim was to examine whether hyperthermia induces changes in transforming growth factor-beta1 (TGF-beta1). Following pretreatment without or with a single or double hyperthermia, pancreatitis was induced by application of cerulein or DBTC. Pancreatic HSP and TGF-beta1 expression were studied by immunoblotting. Pancreas injury was assessed by light microscopy and serum pancreatic enzyme activity. Hyperthermia as well as DBTC induced HSP72, whereas cerulein did not. A double hyperthermia led to a further increase in HSP72 compared to a single heat stress. In both models, hyperthermia significantly reduced pancreatic injury. Although a double hyperthermia slightly decreased the severity of cerulein pancreatitis compared to a single heat treatment, an improved pancreas protection against DBTC cytotoxicity was not achieved. We also found that hyperthermia induces the expression of TGF-beta1. In conclusion, hyperthermia preconditioning exerts protective effects against two pathophysiologically different types of pancreatitis by a mechanism that involves the up-regulation of HSP70 isoforms as well as TGF-beta1. PMID- 11215750 TI - Impaired fecal elastase excretion in uremic pancreopathy. AB - To evaluate pancreatic exocrine function in uremia, 25 patients undergoing regular hemodialysis without clinical evidence of pancreatic disease and 25 healthy control subjects were studied by fecal elastase 1 and chymotrypsin. Abdominal ultrasonography and measurement of serum lipase, calcium, phosphate, and parathormone were also carried out. Fecal elastase was significantly lower (P < 0.001) in patients than in controls. Abnormally low values were found in 12/25 patients of whom six had values <100 microg/g. Fecal chymotrypsin was significantly lower (P < 0.05) in patients than in controls, with lower than normal values found in 10/25 patients. Fecal elastase was not related to the serum calcium, phosphate, or parathormone levels or to the period of dialysis. In patients serum lipase was normal or slightly elevated (<300 units/liter), and there was no evidence of pancreatic disease at ultrasound examination. The results lend further support to the existence of pancreatic function impairment in a significant number of patients with renal failure despite the absence of clinical and morphological evidence of pancreatic disease. PMID- 11215751 TI - Vitamin E protects neurons against oxidative cell death in vitro more effectively than 17-beta estradiol and induces the activity of the transcription factor NF kappaB. AB - Antioxidants can function as powerful protectants for neurons in vitro. Here, the neuroprotective activity of lipophilic free radical scavengers synthetic (+/-) alpha-tocopherol (synthetic vitamin E) and natural (+) alpha-tocopherol (natural vitamin E) against oxidative stress was investigated and compared to the neuroprotective effect of the female sex hormone estradiol. Employing mouse clonal hippocampal HT22 cells and rat cerebellar granule neurons, we found that both types of alpha-tocopherol exerted a higher neuroprotective antioxidant activity than 17-beta estradiol. At concentrations as low as 100 nM, synthetic (+/-) alpha-tocopherol and natural (+) alpha-tocopherol protected neurons effectively against the oxidative cell death caused by the Alzheimer's disease associated amyloid beta protein, hydrogen peroxide, and the excitatory amino acid glutamate. Moreover, vitamin E induced the activity of the redox-sensitive transcription factor NF-kappaB, which is involved in the control of nerve cell survival and, therefore, may play also a role in vitamin E-induced neuroprotection. These results may have implications regarding the prevention and treatment of oxidative stress-related degenerative disorders such as Alzheimer's disease. PMID- 11215752 TI - The novel type B MAO inhibitor PF9601N enhances the duration of L-DOPA-induced contralateral turning in 6-hydroxydopamine lesioned rats. AB - The present study examined the effect of the highly potent and selective MAO B inhibitor PF9601N on L-DOPA-induced rotational behavior in unilateral nigrostriatal 6-hydroxydopamine lesioned rats. Three doses of PF9601N (20, 40 and 60mg/kg) were administered 30 min before an injection of L-DOPA (25mg/kg), and both contralateral and ipsilateral rotational behavior was measured. In addition, we also studied the effect produced by another MAO B inhibitor, deprenyl (20mg/kg), the MAO A inhibitor, clorgyline (20mg/kg), and the dopamine reuptake inhibitor, GBR2909 (7.5 mg/kg) on L-DOPA-induced rotational behavior. The results showed that PF9601N plus L-DOPA significantly enhanced the duration of contralateral rotational behavior with respect to L-DOPA plus vehicle in a dose related manner. At the dose of 40 and 60mg/kg, PF9601N produced significantly more overall contralateral turning than L-DOPA plus vehicle, and at the dose of 60mg/kg, PF9601N produced significantly more turning behavior than L-DOPA plus deprenyl. These results suggest that PF9601N may be used as a novel tool in the treatment of Parkinson's disease. PMID- 11215753 TI - Sexual differences and estrous cycle in methamphetamine-induced dopamine and serotonin depletions in the striatum of mice. AB - Four consecutive doses (10 mg/kg) of methamphetamine, s.c., produced a substantial striatal dopamine depletion in both sexes of BALB/c and C57BL/6J mice. Male C57BL/6J mice exhibited greater dopamine depletions in the striatum compared to female C57BL/6J mice. In contrast, male and female BALB/c mice demonstrated an equivalent magnitude of striatal dopamine depletion. Regardless of sex, C57BL/6J mice demonstrated approximately 1.4 to 2.2 times greater dopamine depletions in the striatum compared to BALB/c mice. Moreover, methamphetamine caused 4 times greater serotonin depletions in male as opposed to female BALB/c mice while sparing either sex of the C57BL/6J mice. Furthermore, female mice of both strains appeared to have the greatest basal dopamine levels during proestrus and the lowest basal dopamine levels during diestrus. Likewise, female mice of both strains exhibited the lowest dopamine depletions in the striatum when the dosing regimen of methamphetamine started at proestrus whereas the greatest dopamine depletions in the striatum occurred when the regimen started during diestrus. These results suggest that sex hormones and other modulating factors may play a role in methamphetamine-induced dopamine and serotonin neurotoxicity. PMID- 11215754 TI - SCH 23390 enhances exogenous L-DOPA decarboxylation in nigrostriatal neurons. AB - Exogenous L-DOPA enhances dopamine metabolism in the intact and denervated striatum, and is the treatment of choice for Parkinsonism. Aromatic L-amino acid decarboxylase (AAAD) converts L-DOPA to dopamine. Blockade of dopamine D1-like receptors increases the activity of AAAD in both intact and denervated striatum. A single dose of SCH 23390, a dopamine D1-like receptor antagonist, increases the activity of AAAD in the striatum and midbrain and induces small changes in dopamine metabolism. When L-DOPA is administered after SCH 23390, there is a significant increase in the formation of 3,4-dihydroxyphenylacetic acid and dopamine turnover in striatum and midbrain compared to L-DOPA alone, suggesting further enhancement of dopamine metabolism. When the studies are repeated in the MPTP mouse model of Parkinson's disease, there is significantly more dopamine metabolism in the striatum of lesioned mice pretreated with SCH 23390 than in a comparison group treated with L-DOPA alone. These studies suggest that it may be possible to enhance the conversion of L-DOPA to dopamine in Parkinson's disease patients by administering substances that augment brain AAAD. PMID- 11215755 TI - Normal cerebrospinal fluid levels of insulin in patients with Parkinson's disease. AB - We compared CSF levels insulin, measured by a Radioimmunoanalysis method, in 24 patients with Parkinson's disease (PD) and 21 matched controls. The CSF insulin levels did not differ significantly between PD patients and controls. CSF insulin levels were not correlated with age, age at onset, duration of the disease, scores of the Unified Parkinson Disease Rating Scale of the Hoehn and Yahr staging in the PD group. Antiparkinsonian therapy did not influence significantly and CSF levels of insulin. These results suggest that CSF insulin concentrations are not a biological marker of PD and its severity. PMID- 11215756 TI - Modulation of APP processing and secretion by okadaic acid in primary guinea pig neurons. AB - Primary cultures of guinea pig neurons were used as a model system to study the influence of the protein phosphatase inhibitor okadaic acid (OA) on the secretion, processing and phosphorylation of the amyloid precursor protein (APP). This primary cell culture system mimics more closely than other cell culture systems the human in vivo condition, as guinea pig APP is 98% homologous to human APP at the protein level, identical regarding the Abeta sequence and is processed in a similar manner as human APP. Both intracellular and secreted APP was upregulated by OA treatment (0.3 nM-10 nM) of 14 days old cultures in a concentration dependent manner while the amount of Abeta in the medium was decreased. OA treatment did not affect cell membrane integrity of primary neurons but induced DNA fragmentation. Phosphorylation of APP was unchanged by the low OA concentration used. These results show that OA treatment of guinea pig primary cultures might be used as a model to study the effects of modulation of signal transduction on secretion and processing of APP. PMID- 11215757 TI - Growth-associated protein GAP-43 in the frontal cortex and in the hippocampus in Alzheimer's disease: an immunohistochemical and quantitative study. AB - We studied the growth-associated protein, GAP-43 (also called neuromodulin and B 50) in post-mortem brain tissue using immunohistochemistry and quantitative Western blotting, from patients with Alzheimer's disease (AD) and age-matched control subjects. By immunohistochemistry, we found a clear reduction of GAP-43 in the frontal cortex, while in the hippocampus, there was a marked reduction in some areas (dentate molecular layer, stratum moleculare and radiale of CA1 and CA4), while not in other areas (stratum lacunosum, pyramidale and oriens of CA1). Moreover, in the hippocampus, neuritic staining was prominent, and was often associated with senile plaques. Quantitative analysis showed that GAP-43 was significantly reduced in AD, both in the frontal cortex (70% of the control value, p < 0.01) and in the hippocampus (81% of the control value, p < 0.05). In the frontal cortex, there was a significant negative correlation between GAP-43 and duration of dementia (r = -0.58; p < 0.02) and a positive correlation between GAP-43 and the synaptic vesicle-specific protein rab3a (r = 0.62; p < 0.05), while no such correlation were found in the hippocampus. In contrast, a significant positive correlation was found between GAP-43 and the number of senile plaques in the hippocampus (r = 0.64; p < 0.05), but not in the frontal cortex. GAP-43 is known to be involved in maintenance of synapses and in neuritic regeneration. Our findings may suggest that in the frontal cortex, GAP-43 levels decline as a consequence of the synaptic degeneration, while in the hippocampus, sprouting processes, involving GAP-43, are active. PMID- 11215758 TI - Haloperidol-induced neurotoxicity--possible implications for tardive dyskinesia. AB - Tardive dyskinesia (TD) is one of the major side effects of long term neuroleptic treatment. The pathophysiology of this disabling and commonly irreversible movement disorder is still obscure. The traditional concept of supersensitivity of striatal dopamine receptors as the mechanism involved in the development of TD is not satisfying, and current studies have focused on the role of neuroleptic induced neuronal toxicity in the development of TD. We performed a series of experiments to gain a better understanding on the mechanisms involved in induction of TD. We have evaluated the direct neurotoxic effect of haloperidol (HP), a widely--used neuroleptic drug, and its three metabolites, in mouse neuronal cultures and in PC-12 cells. We found that the features of HP-induced cell death were apoptotic rather than necrotic, as indicated by different DNA staining methods and specific caspases inhibitors. Moreover, cotreatment with antioxidants such as vitamin E and N-acetylcysteine (NAC) significantly protected the cultures. Further studies on the mechanisms underlying HP-induced toxicity may lead to the development of new neuroprotective therapeutic strategies. PMID- 11215759 TI - An association study between two missense variations of the benzodiazepine receptor (peripheral) gene and schizophrenia in a Japanese sample. AB - The benzodiazepine receptor (peripheral) (BZRP) mainly localized on glial cells plays a role in neurosteroid synthesis, and increases with glial proliferation. We have recently reported a significant decrease in the density of BZRP labeled by [3H] PK 11195 in the postmortem brain of chronic schizophrenics, suggesting that dysfunctions of the BZRP are involved in the pathophysiology of schizophrenia. We screened 11 patients with schizophrenia and 10 controls, which were used in a previous postmortem study, for their genomic sequences of the BZRP gene in order to find DNA sequence variations. One novel missense polymorphism (His162Arg) and another previously reported missense mutation (Ala147Thr) were detected. An association study of the identified variations was then performed in an extended Japanese sample of 304 schizophrenic patients and 369 controls. While there was an increased tendency in the frequency of the 162Arg allele of schizophrenics compared to that of the controls (p = 0.0603), no statistically significant association with schizophrenia was observed in the Ala147Thr allele (p = 0.1016). These results do not suggest that the two missense polymorphisms play a major role in the genetic predisposition of schizophrenia in the Japanese sample. PMID- 11215760 TI - Abnormal protein phosphorylation in post-mortem brain tissue from bipolar patients. AB - Abnormal phosphorylation has been proposed to be involved in the pathogenesis of affective disorders. The present study investigated basal and cAMP-stimulated endogenous protein phosphorylation in human post-mortem brain tissue from bipolar and schizophrenic patients. Furthermore, basal kinase activity and stimulated protein kinase A activity were measured. The frontal and occipital cortex were analysed. Using [gamma-32P]ATP as phosphate donor, basal and cAMP-stimulated phosphorylation of endogenous proteins was measured in the absence or presence of 8-Br-cAMP, respectively. The proteins were separated on SDS-gels and the radioactivity in the individual bands was measured. We observed a significant reduction of 32P incorporation in three protein substrates (15, 16 and 21 kD) in frontal cortex of bipolar patients. However, there were no differences in the PKA activity between any of the groups. The present study demonstrates abnormal phosphorylation of specific proteins in brain tissue obtained from bipolar patients in comparison to schizophrenics and controls. PMID- 11215761 TI - Hair bundle profiles along the chick basilar papilla. AB - Cochlear hair cells play a central role in the transduction of sound into neural output. Anatomical descriptions of these cells, and their protruding hair bundles, are of fundamental interest since hair cell transduction is dependent on hair bundle micromechanics and hair bundle micromechanics depends on hair bundle morphology. In this paper, we describe quantitatively changes in the staircase profile of the hair bundle along the apical portion of the chick's basilar papilla. Images of hair cells from 8 discretely dissected segments of the apical 3rd of the basilar papilla were archived, and the profile contour outlined by the tips of the stereocilia was digitised and curves were fitted by linear and power equations. The hair bundles of tall hair cells exhibited both linear and curvilinear profiles, which were equally distributed along the papilla. All short hair cells in our sample had straight contours. The differences in hair bundle shape among the tall hair cells may lead to differential susceptibility to injury and some variance in the current-displacement transduction curves due to differences in the translation of forces throughout the hair bundle. PMID- 11215762 TI - Separation between the digestive and the respiratory lumina during the human embryonic period: morphometric study along the tracheo-oesophageal septum. AB - An isolated tracheo-oesophageal fistula could be caused by close proximity of the epithelia of both organs (O'Rahilly & Muller, 1984; Kluth et al. 1987) at certain embryonic stages, the most frequent location being the tracheal bifurcation. Thus the relative position and degree of separation between the digestive and the respiratory tubes throughout their development may be relevant to the origin of this anomaly. The aim of this study was to analyse along the different segments of the tracheo-oesophageal septum (TES) where the closest relationship between both lumina occurred and what degree of separation was present at each segment. Computer imaging techniques were applied on cross sections of a graded series of normal human embryos (Carnegie stages (CS) 13-23). In addition, the differentiation of the primitive TES was also studied (from CS 12) by light microscopy. Between CS 13 and 16 both tubes tended to separate (phase of separation), principally at the proximal segments of the laryngopharyngeal and the tracheo-oesophageal portions of the TES. During this phase the separation between the trachea and oesophagus was wider than between the larynx and pharynx. From CS 17 to CS 23 the digestive and respiratory lumina reached their widest separation at different levels of the laryngopharyngeal portion. Below these levels they tended to come closer together, principally at the proximal segment of the tracheo-oesophageal portion, but also at the distal part of the laryngopharyngeal portion. During this phase of approximation they reached their closest relationship at the proximal (CS 17) and the distal (from CS 18) segments of the tracheo-oesophageal portion. When finally the distal segment of the trachea (which includes the bifurcation) comes closest to the oesophagus, the coats of both organs have already undergone an appreciable differentiation. According to these observations, the origin of the most frequent isolated tracheo oesophageal fistula at the bifurcation region could not be explained from the normal development of the TES. PMID- 11215763 TI - The hip joint: the fibrillar collagens associated with development and ageing in the rabbit. AB - The fibrillar collagens associated with the articular cartilages, joint capsule and ligamentum teres of the rabbit hip joint were characterised from the 17 d fetus to the 2-y-old adult by immunohistochemical methods. Initially the putative articular cartilage contains types I, III and V collagens, but when cavitation is complete in the 25 d fetus, type II collagen appears. In the 17 d fetus, the cells of the chondrogenous layers express type I collagen mRNA, but not that of type II collagen. Types III and V collagens are present throughout life, particularly pericellularly. Type I collagen is lost. In all respects, the articular cartilage of the hip joint is similar to that of the knee. The joint capsule contains types I, III and V collagens. In the fetus the ligamentum teres contains types I and V collagens and the cells express type I collagen mRNA; type III collagen is confined mainly to its surface and insertions. After birth, the same distribution remains, but there is more type III collagen in the ligament, proper. The attachment to the cartilage of the head of the femur is marked only by fibres of type I collagen traversing the cartilage; the attachment cannot be distinguished in preparations localising types III and V collagens. The attachment to the bone at the lip of the acetabulum is via fibres of types I and V collagens and little type III is present. The ligament is covered by a sheath of types III and V collagens. Type II collagen was not located in any part of the ligamentum teres. The distribution of collagens in the ligamentum teres is similar to that in the collateral ligaments of the knee. Its insertions are unusual because no fibrocartilage was detected. PMID- 11215764 TI - Fos expression in the midbrain periaqueductal grey after trigeminovascular stimulation. AB - There is an accumulating body of evidence suggesting that the periaqueductal grey (PAG) is involved in the pathophysiology of migraine. Positron emission tomography (PET) studies in humans have shown that the caudal ventrolateral midbrain, encompassing the ventrolateral PAG, has activations during migraine attacks. The PAG may well be involved not only through the descending modulation of nociceptive afferent information, but also by its ascending projections to the pain processing centres of the thalamus. In this study the intranuclear oncogene protein Fos was used to mark cell activation in the PAG following stimulation of the trigeminally-innervated superior sagittal sinus (SSS) in both cats and in nonhuman primates (Macaca nemestrina). Fos expression in the PAG increased following stimulation to a median of 242 cells (interquartile range 236-272) in the cat and 155 cells (range 104-203) in the monkey, compared with control levels of 35 cells (21-50) and 26 cells (18-33), respectively. Activation was predominantly in the ventrolateral area of the caudal PAG suggesting that the PAG is involved following trigeminally-evoked craniovascular pain. PMID- 11215765 TI - A comparative analysis of the differential spatial and temporal distributions of the large (aggrecan, versican) and small (decorin, biglycan, fibromodulin) proteoglycans of the intervertebral disc. AB - This study provides a comparative analysis of the temporal and spatial distribution of 5 intervertebral disc (IVD) proteoglycans (PGs) in sheep. The main PGs in the 2 and 10 y old sheep groups were polydisperse chondroitin sulphate and keratan sulphate substituted species. Their proportions did not differ markedly either with spinal level or disc zone. In contrast, the fetal discs contained 2 slow migrating (by composite agarose polyacrylamide gel electrophoresis, CAPAGE), relatively monodisperse chondroitin sulphate-rich aggrecan species which were also identified by monoclonal antibody 7-D-4 to an atypical chondroitin sulphate isomer presentation previously found in chick limb bud, and shark cartilage. The main small PG detectable in the fetal discs was biglycan, whereas decorin predominated in the 2 and 10 y old IVD samples; its levels were highest in the outer annulus fibrosus (AF). Versican was most abundant in the AF of the fetal sheep group; it was significantly less abundant in the 2 and 10 y old groups. Furthermore, versican was immunolocalised between adjacent layers of annular lamellae suggesting that it may have some role in the provision of the viscoelastic properties to this tissue. Versican was also diffusely distributed throughout the nucleus pulposus of fetal IVDs, and its levels were significantly lower in adult IVD specimens. This is the first study to identify versican in ovine IVD tissue sections and confirmed an earlier study which demonstrated that ovine IVD cells synthesised versican in culture (Melrose et al. 2000). The variable distribution of the PGs identified in this study provides further evidence of differences in phenotypic expression of IVD cell populations during growth and development and further demonstrates the complexity of the PGs in this heterogeneous but intricately organised connective tissue. PMID- 11215766 TI - Cerebellar connections to the dorsomedial and posterior nuclei of the hypothalamus in the rat. AB - The stimulation or ablation of cerebellar structures has produced a variety of visceral responses, indicating a cerebellar role in visceral functions. Studies using anterograde and retrograde tracing methods have revealed connections between the hypothalamus and cerebellar structures. The aim of this study is to investigate the cerebellar connections of the dorsomedial (DMH) and posterior hypothalamic nuclei using retrograde axonal transport of horseradish peroxidase (HRP). In the present study, micro-injection of HRP restricted within the borders of the DMH showed that the projections of this nucleus are not uniform throughout its extent. The posterior DMH receives projections from the cerebellum, whereas the anterior DMH does not. These projections were from the (greatest to least concentration) lateral (dentate), anterior interposed (emboliform), and medial (fastigial) cerebellar nuclei. In addition, both the anterior and posterior DMH receive projections from various areas of the brainstem which confirms earlier studies and provides detailed descriptions. This study also demonstrates the distribution of labelled neurons to cerebellar and brainstem nuclei following HRP injection into the posterior hypothalamic nucleus. It provides clear evidence for a direct cerebellar nuclei-posterior DMH and cerebellar nuclei-posterior hypothalamic nucleus connections. We suggest that the brainstem reticular nuclei and other connections, such as the solitary, trigeminal and vestibular nuclei, of both DMH and posterior hypothalamus may contribute to the indirect cerebellohypothalamic connections. These observations offer a new perspective on the question of how the cerebellum may influence autonomic activity. PMID- 11215768 TI - The structural organisation of sperm head components of the wombat and koala (suborder: Vombatiformes): an enigma amongst marsupials. AB - The sperm head structural organisation of the koala and hairy-nosed wombat, and the effects of varying concentrations of the ionic detergent, Triton X-100, on its component parts, were determined by electron microscopy. Although alike in form between the 2 species, the sperm nucleus of the former, but not the latter, had nuclear vacuoles and appeared to be more easily dispersed by the Triton X 100. The structure of the acrosome of the spermatozoon was similar between the 2 species and, in both, previously undescribed thin posterior and lateral segments were found to be present. It is suggested that this thin segment may facilitate sperm-zona and/or sperm-oolemma binding and fusion. PMID- 11215767 TI - Carbohydrate moieties of the interstitial and glandular tissues of the amphibian Pleurodeles waltl testis shown by lectin histochemistry. AB - The amphibian testis is a useful model because of its zonal organisation in lobules, distributed along the cephalocaudal axis, each containing a unique germ cell type. Sperm empty lobules form the so-called glandular tissue at the posterior region of the gonad. Androgen production is limited to the cells of the interstitial tissue surrounding lobules with spermatozoa bundles and to the cells of the glandular tissue. In this work, we have studied the distribution of terminal carbohydrate moieties of N- and O-linked oligosaccharides in the interstitial and glandular tissue of the Pleurodeles waltl testis, by means of 14 lectins combined with chemical and enzymatic deglycosylation pretreatment. Some differences in glycan composition between the interstitial and the glandular tissue have been detected. Thus in both tissues, N-linked oligosaccharides contained mannose, Gal(beta1,4)GlcNAc, and Neu5Ac(alpha2,3)Gal(beta1,4)GlcNAc, while O-linked oligosaccharides contained Con A-positive mannose, Gal(beta1,3)GalNAc, Gal(beta1,4)GlcNAc, Neu5Ac(alpha2,3)Gal(beta1,4)GlcNAc, and WGA-positive GlcNAc. Fucose was also detected in both tissues. However, GlcNAc on N-linked oligosaccharides and GalNAc and Neu5Ac(alpha2,6)Gal/GalNAc on both N- and O-linked oligosaccharides were found only in the interstitial tissue. As glandular tissue cells arise from the innermost cells of interstitial tissue that surround lobules, the differences in the glycan composition of interstitial and glandular tissue shown in this work may be related to the start of androgen synthesis when steroid hormone (SH)-secreting cells develop. PMID- 11215769 TI - Glial fibrillary acidic protein and vimentin immunoreactivity of astroglial cells in the central nervous system of adult Podarcis sicula (Squamata, Lacertidae). AB - The present immunoperoxidase cytochemical study describes the distribution of glial intermediate filament molecular markers, glial fibrillary acidic protein (GFAP) and vimentin, in the brain and spinal cord of the adult lizard, Podarcis sicula. GFAP immunoreactivity is abundant and the positive structures are mainly represented by fibres of different lengths which are arranged in a rather regular radial pattern throughout the CNS. They emerge from generally immunopositive radial ependymoglia and are directed from the ventricular wall towards the meningeal surface. The glial fibres give origin to endfeet which are apposed to the blood vessel walls and subpial surface where they form the continous perivascular and subpial glia envelopes, respectively. In the optic tectum and spinal cord, star-shaped astrocytes coexist with radial glia. In the spinal cord, cell bodies of immunopositive radial glia are displaced from the ependyma. While vimentin immunoreactive elements are almost completely absent in the brain except for a few diencephalic radial fibres, the spinal cord ependyma exhibits a clearly vimentin positivity and no GFAP staining. In the Podarcis CNS the immunocytochemical response of the astroglial intermediate filaments appears typical of mature astroglia cell lineage since it fundamentally expresses GFAP immunoreactivity. Moreover, this immunocytochemical study shows that the Podarcis fibre pattern with predominant radial glial cells is morphologically more immature than in avians and mammalians, a condition suggesting that reptiles represent a fundamental step in the phylogenetic evolution of vertebrate astroglial cells. PMID- 11215770 TI - The existence of the vomeronasal organ in postnatal chimpanzees and evidence for its homology with that of humans. AB - It is currently thought that New World monkeys, prosimians, and humans are the only primates to possess vomeronasal organs (VNOs) as adults. Recent studies of the human VNO suggest that previous investigations on Old World primates may have missed the VNO. We examined nasal septa from the chimpanzee (Pan troglodytes) grossly and histologically for comparison with nasal septa from humans, Old World monkeys (Macaca fascicularis, M. nemistrina) and prosimian primates (Microcebus murinus, Otolemur garnettii). Grossly, chimpanzees had depressions on the nasal septum similar to fossae reported anterior to the VNO openings in humans. Histologically, chimpanzees and humans had bilateral epithelial tubes which were above the superior margin of the paraseptal cartilages (vomeronasal cartilage homologue). The epithelial tubes had a homogeneous ciliated epithelium. These structures were thus positionally and structurally identical to the human VNO and unlike the well-developed prosimian VNOs which were surrounded by vomeronasal cartilage. Macaques had no structures which resembled the VNO of either the prosimians or humans. The results demonstrate that the VNO is present postnatally in the chimpanzee and is almost identical to the human VNO in its anatomical position and histological structure. This in turn suggests that the reported absence of the VNO in at least some adult Old World primates is artifactual, and that further study may provide evidence for its existence in other species. PMID- 11215771 TI - Semiquantitative analysis of collagen types in the hypertrophied left ventricle. AB - Cardiac fibrosis is a characteristic feature of left ventricular hypertrophy. The aim of this study was to develop a simple and accurate method to analyse collagen accumulation, taking into account the variation in cardiac muscle fibre orientation and nonuniform collagen distribution. This technique was used to determine the amount and types of collagen that accumulate during pressure overload cardiac hypertrophy. These data were correlated with myocyte size, and with the diastolic stress-strain relationship of the intact myocardium. Myocyte size was significantly increased in the hypertrophied hearts, compared with age and sex matched controls (control 363 +/- 25 microm2 vs experimental 244 +/- 12 microm2; mean +/- S.E., P < 0.05). No overall collagen accumulation was observed in the hypertrophied hearts, but a significant increase in collagen I was found with a reduction in the amount of collagen III in experimental animals. Since no increase in diastolic stiffness of the hearts was observed, these results indicate that an increase in the overall collagen content of the heart, rather than the upregulation of a specific type, may be necessary to cause diastolic dysfunction. PMID- 11215772 TI - Actin polymerisation during morphogenesis of the acrosome as spermatozoa undergo epididymal maturation in the tammar wallaby (Macropus eugenii). AB - In the tammar wallaby (Macropus eugenii), post-testicular acrosomal shaping involves a complex infolding and fusion of the anterior and lateral projections of the scoop-shaped acrosome into a compact button-like structure occupying the depression on the anterior end of the sperm nucleus. The present study has generated cytochemical and histological evidence to demonstrate that the occurrence of actin filaments (F-actin, labelled by Phalloidin-FITC) in the acrosome of tammar wallaby spermatozoa is temporally and spatially associated with the process of acrosomal shaping in the epididymis, through a pool of monomeric actin (G-actin, labelled by Rh-DNase I) present in the acrosome throughout all stages of epididymal maturation. F-actin was not detected in the acrosome of testicular spermatozoa, but was found in the infolding and condensing acrosome of caput and corpus epididymal spermatozoa. When the spermatozoa completed acrosome shaping in the cauda epididymidis, F-actin disappeared from the acrosomal area. The strong correlation between the occurrence of F-actin and the events of acrosomal shaping suggested that the post-testicular shaping of the acrosome might depend on a precise succession of assembly and disassembly of F actin within the acrosome as the spermatozoa transit the epididymis. Thus, actin filaments might play a significant role in the acrosomal transformation, as they are commonly involved in morphological changes in somatic cells. PMID- 11215773 TI - Surgical treatment of differentiated thyroid carcinoma in children. AB - INTRODUCTION: A retrospective clinical study was carried out to define the appropriate definitive operation for treating differentiated thyroid carcinoma (DTC) in children. METHODS: During a 24-year period between 1974 and 1997, 18 children younger than 16 years at presentation were histopathologically proven to have DTC in Hacettepe University Children's Hospital, Department of Pediatric Surgery. The clinical characteristics on admission, operative findings, procedures, operative complications, and follow-up results according to definitive operations were compared to find out the appropriate procedure. RESULTS: There were 15 female (83.3%) and 3 male (16.7%) patients yielding a female/male ratio of 5 and the average age being 11.6+/-2.1 years. The definitive operations were near total thyroidectomy, total thyroidectomy, near total thyroidectomy plus excision of the only palpable lymph nodes (EPLN), total thyroidectomy plus EPLN and total thyroidectomy plus modified radical neck dissection (MRND) in 3 (16.7%), 3 (16.7%), 1 (5.5%), 9 (50%), and 2 (11.1 %) patients respectively. Among the patients having undergone near total thyroidectomy, one had recurrences both in the thyroid bed and the cervical lymph nodes. In a patient undergoing almost total thyroidectomy and EPLN, recurrences involving thyroid bed, cervical lymph nodes and lungs were encountered. In 9 patients undergoing total thyroidectomy and EPLN 4 had cervical lymph node recurrences. Complications have included permanent hypoparathyroidism following total thyroidectomy and MRND. Additionally, operations for recurrences resulted in unilateral permanent recurrent laryngeal nerve palsies in two patients. CONCLUSIONS: Total thyroidectomy with evaluation of central compartment, entire jugular chain and region of lower spinal accessory nerve and removal of all identifiable lymph nodes seems to be the most appropriate surgical treatment for DTC encountered in children. PMID- 11215774 TI - The characteristics of mediastinal neuroblastoma. AB - The prognosis of mediastinal neuroblastoma has been reported to be better than for other neuroblastomas. The reason for this is however not clear. Furthermore, a comparison between mediastinal neuroblastoma and the other neuroblastomas has been rarely reported so far. In this study, the characteristics of mediastinal neuroblastoma (84 cases) are investigated and compared with those of other neuroblastomas (440 cases). Regarding clinical factors, the age distribution and the rate of cases detected at mass screening were similar in both groups. According to Evan's staging system, the rates of early stage (I, II) were 62% in the mediastinal neuroblastoma and 38% in the other neuroblastomas (p<0.001). Regarding the biological prognostic factors, a favorable histology based on Shimada's classification was found in 100% (35/35) of the mediastinal neuroblastoma cases and in 85% (112/132) of the other neuroblastoma cases (p<0.05). With regard to N-myc amplification, all of the examined 42 cases in mediastinal neuroblastoma had a N-copy number of less than 10 copies, while 32 of the examined 263 cases (12%) in the other neuroblastomas had an amplification of N-myc of more than 10 copies (p<0.05). The 5-year survival rates were 78% in the mediastinal neuroblastoma and 59% in the other neuroblastomas, respectively. Of the cases who underwent an incomplete resection of primary tumors in localized neuroblastoma, the 5-year survival rate of the mediastinal neuroblastoma cases was significantly more favorable than that of the other neuroblastomas. The majority of mediastinal neuroblastoma cases showed an early stage and favorable prognostic factors. It is likely that the clinical and biological prognostic factors of the tumor are therefore more closely correlated with the outcome of mediastinal neuroblastoma rather than the degree of the surgical resection. Regarding the treatment for mediastinal neuroblastoma, it is most important to evaluate the biology of the tumor after surgical resection. PMID- 11215775 TI - Gastroesophageal reflux and diaphragmatic motility after repair of congenital diaphragmatic hernia. AB - At the Department of Pediatric Surgery in Graz, 31 boys and 23 girls were operated on for congenital diaphragmatic hernia (CDH) from 1978 to 1994. In 49 patients the defect was on the left, in five on the right side. In 46 cases, the hernia was diagnosed within the first week of life; in eight children at a later date. 19 children (35%) died. 25 of the 35 survivors (71%) came to a follow-up examination on average 9.4 (1-17) years after the operation. 24 h pH-monitoring or manometry and Upper G.I. series revealed pathological gastroesophageal reflux (GER) in 16 patients. Nine children were treated conservatively; in seven patients an antireflux procedure was performed. A thoracic position of the stomach or left liver lobe, presence of a hernial sac, gestational age, prenatal diagnosis, use of a patch or severity of lung hypoplasia did not significantly influence the incidence of GER. In three patients, a hiatal hernia was found. The motility of the diaphragm was documented with M-mode sonography (n = 18); a restricted motility could be demonstrated in five patients. GER is very common in patients after repair of CDH. We recommend long-term follow-up with special interest in respect of GER. PMID- 11215776 TI - Long-term investigations after pyloromyotomy for infantile pyloric stenosis. AB - Between 1919 and 1941, 71 infants suffering from pyloric hypertrophy were operated on by Ramstedt performing an extramucosal pyloromyotomy. Of these patients, we could identify and investigate 41. Four out of 31 long-term surviving patients have been Billroth II-resected (BII). One of these needed re resection because of an anastomotic ulcer. None of all the long-term survivors developed a carcinoma. Two patients were treated conservatively because of gastritis and one because of esophagitis. All patients, except the one requiring re-resection and one suffering from maldigestion, were absolutely free of complaints. The average time between operation and re-checking was 57 years. The oldest patient was examined 72 years after the operation. PMID- 11215777 TI - Early biliary pseudolithiasis during ceftriaxone therapy for acute pyelonephritis in children: a prospective study in 34 children. AB - The prolonged biological half-life of Ceftriaxone, allowing once-daily dosing, has contributed to the large diffusion of this third-generation cephalosporin in children. Ceftriaxone is known to induce reversible precipitates in the gallbladder of adults and children. A prospective study was conducted during 1997 in 34 children admitted for the treatment of acute pyelonephritis. Ceftriaxone (intravenous daily single-dose of 50 mg/kg under 2g/day) was initially used. A first gallbladder sonogram, performed before the first or second injection, was normal in all cases. A second evaluation was performed before the fifth and last injection. On this second evaluation the presence of one (n = 3) or two gallstones was recorded in 5 children (15%) on a sonogram made after 3 (n = 4) or 5 (n = 1) injections. Their median age was 7 years (range 4 months to 11 years). All five children remained symptom-free and the normalization of the sonographic patterns was constant on the last sonogram performed 2 (n = 1), 3 (n = 2) and 5 months (n = 2) after discontinuation of Ceftriaxone. This study confirms the possibility of precocious biliary lithiasis under Ceftriaxone therapy in childhood and their spontaneous dissolution after discontinuation of the drug. They seem unpredictable and independent of the age, sex in a cohort homogeneous for the nature of the infection, modality of a short- and low-dose therapy. Clinicians and radiologists should be aware of this complication as an etiology of a so-called primary cholelithiasis and to prevent anxiety or unnecessary cholecystectomy. The antibacterial and pharmacokinetic benefits of Ceftriaxone outweigh the problem of reversible biliary pseudolithiasis with this drug. PMID- 11215778 TI - Carcinoid tumors of the appendix in children--epidemiology, clinical aspects and procedure. AB - INTRODUCTION: Incidental detection of a carcinoid tumor of the appendix after appendectomy is often accompanied by uncertainty about the further procedure. The tumor frequency in our own patient population, the further course in these children and a practicable follow-up protocol have to be determined. PATIENTS AND METHODS: All appendectomies performed between January 1, 1982, and December 31, 1996, were retrospectively evaluated with regard to carcinoids, monitoring the clinical course, and follow-up of the patients involved. RESULTS: A total of 4747 appendectomies were performed, 8 children had a histologically manifest carcinoid (0.169%). All patients were symptom-free in the further course, no metastases or signs of a carcinoid were documented during a mean follow-up period of 6.6 years. CONCLUSION: The youngest patient with a metastasizing carcinoid tumor of the appendix reported in the literature was 19 years old. Nevertheless, all younger patients should undergo regular follow-ups; this is done in our department by serum serotonin and chromogranin A determination. PMID- 11215779 TI - Proximal segment histology of resected bowel in Hirschsprung's disease predicts postoperative bowel function. AB - The authors present an overview of 101 patients operated for Hirschsprung's disease by Rehbein procedure. Special attention is directed to the histomorphological findings in the proximal segment of the resected bowel specimens. A strong link was confirmed between these specific features and postoperative bowel function. A histologically regular proximal bowel segment generally predicted good postoperative bowel function with a constipation rate of 10.5%. In patients with intestinal neuronal dysplasia (IND) of the proximal segment the overall clinical result remained unchanged, although the constipation rate rose to 17.8%. Postoperative bowel function was seriously affected in cases characterized by proximal segment hypoganglionosis with a constipation rate of 23.1% and an additional 7.7% with encopresis. Finally, the distinct group of children with aganglionosis of the proximal segment followed a complicated postoperative course with secondary bowel resections and recurrent episodes of enterocolitis. In addition, the authors state their general observation that histological findings become less important whenever a more extensive resection than left hemicolectomy is required. Discussing the results, guidelines are given to further patient treatment once the particular proximal segment histology is diagnosed. PMID- 11215780 TI - Quantitation of defecation function using radionuclide artificial stool in children with chronic constipation. AB - We aimed to investigate the value of scintigraphically determined evacuation fraction (EVF) as an objective follow-up criterion in medically treated children with chronic constipation, and to evaluate the relation between patients' symptoms and rectal emptying rate. Thirty children (m: 22, f: 8, mean age: 8.9 +/ 0.9 year) suffering from chronic constipation were assessed by scintigraphic evacuation study. All patients underwent anal manometric and scintigraphic examinations before their therapy was started. During 3 months, they received conventional laxative treatment for constipation, and scintigraphic studies were repeated in 20 of 30 patients. Scintigraphic examinations consisted of instillation of artificial stool into the rectum up to the volume impending rectal evacuation, and acquisition of pre- and post-evacuation images. EVF values were then calculated from the images using a fixed region of interest. All of the patients had high resting anal canal pressure (75 +/- 12 mmHg) and had positive rectoanal inhibitory reflex. In 14/20 patients (70%) who benefited from therapy, mean EVF changed from 43.6% to 62.2% (p < 0.001), while decreasing in 6120 who did not benefit. The volume arousing rectal evacuation was significantly lower at the second scintigraphic study (261 +/- 98 ml) than the first study (354 +/- 138 ml) (p < 0.05). As a conclusion: 1) EVF was low in chronically constipated children, 2) it was improved after conventional laxative treatment and, 3) radionuclide EVF determination may be a useful method for follow-up. PMID- 11215781 TI - Type 1-primary cutaneous meningioma of the scalp. AB - Type 1-primary cutaneous meningioma is a rare and often clinically unsuspected lesion of the scalp, forehead or paravertebral region which occurs at birth or during childhood. The pathogenesis of these lesions still remains uncertain. Several authors have emphasized that type 1-cutaneous meningiomas are not real tumors but sequestrated meningoceles or heterotopic meningeal nodules of the skin. Nevertheless, the search for an intracranial or intravertebral connection should be carried out. We describe the clinical and pathological features of a congenital type 1-meningioma of the vertex. No cranial defect or intracranial tumor was found. However, the cutaneous lesion was directly linked to a large cranial vein. The purpose of this study was to illustrate this rare lesion and to indicate the possible surgical risks and the pathological characteristics. PMID- 11215782 TI - Giant-cell fibroblastoma and dermato fibro sarcoma protuberans: the same tumoral spectrum? Report of two cases of association in children. AB - We describe two cases of giant-cell fibroblastoma (GCF) with dermato fibro sarcoma protuberans (DFSP) component, occurring in two children in a chest wall localization. One case recurred 1 year later. The two patients were tumor-free 12 and 8 years later. GCF is a rare mesenchymal cutaneous and subcutaneous tumor reported mostly in the first two decades of life. Dermato fibro sarcoma protuberans, occurring preferentially in adults, is a rare skin tumor with a pronounced tendency to local recurrence. Some cases of association of recurrence of GFC under the form of DFSP have been reported, raising the question of a continuum between the two tumors. The treatment of choice of the two tumors is a wide local excision. PMID- 11215783 TI - Effective percutaneous transhepatic biliary drainage for cystic dilatation of the intrahepatic biliary system in biliary atresia: a case report. AB - We report on a 16-year old girl with postoperative biliary atresia developing cystic dilatation of the intrahepatic biliary system (CDIB) with abdominal pain, which was relieved after percutaneous transhepatic biliary drainage (PTBD). A cyst was detected in segment 4 of the liver at the age of 14 years. She developed severe right hypochondralgia, subfever and liver dysfunction. Percutaneous cholangiogram showed a solitary cyst without communication and a PTBD tube was placed within the cyst. After lavage of the cyst through PTBD, CDIB was re communicated with the intestine and the pain was relieved with reduction of the cyst size. From this experience, PTBD may be a less invasive treatment as the first choice for non-communicating CDIB and may alleviate the symptoms when recommunication with the intestine is obtained. PMID- 11215784 TI - Internal drainage into an Onlay-Roux-en-Y jejunal loop in isolated pancreatic injury with ductal transection: short-term and long-term follow-up in two pediatric cases. AB - Two pediatric cases of isolated pancreatic injury treated by internal drainage into an Onlay-Roux-en-Y jejunal loop are reported. The discussion concerns the difficulties of early diagnosis, the importance of endoscopic retrograde cholangiopancreatography (ERCP) in surgery and the reasons for the choice of internal drainage by Onlay-Roux-en-Y jejunal loop in our two cases. PMID- 11215785 TI - A case of mesenteric cysts caused by abdominal tuberculosis. AB - We report on a 10-year old boy suffering from chronic abdominal pain. Clinical examination and imaging modalities revealed that the patient had mesenteric cysts. Exploratory laparotomy revealed two mesenteric cysts of various size and multiple enlarged mesenteric lymph nodes. M. tuberculosis was identified and histology of the specimens proved the existence of abdominal tuberculosis. PMID- 11215786 TI - Meconium periorchitis: case report and literature review. AB - Meconium periorchitis (MPO) is an uncommon entity associated with healed meconium peritonitis. The typical presentation is soft hydrocele at birth which becomes harder in weeks as the meconium calcifies. It mimics a scrotal mass, and, without knowledge of this rare disease, this may lead to unnecessary surgery. Both the masses and the calcifications have the tendency to resolve spontaneously without compromising the testicle. Sonographic features together with an abdominal plain film are diagnostic, and visualization of the normal testicle may be helpful in differentiating this tumor-like lesion from scrotal tumors. A case of a meconium periorchitis is reported on and the radiological and histological features are discussed with a literature review on the subject. PMID- 11215787 TI - Certification of poliomyelitis eradication--Western Pacific Region, October 2000. AB - On October 29, 2000, the Regional Commission for the Certification of Poliomyelitis Eradication certified that the Western Pacific Region (WPR) of the World Health Organization (WHO) is free of indigenous wild poliovirus transmission. The last known case of indigenous poliovirus transmission occurred in Cambodia in March 1997 in a 15-month-old girl. WPR is the second of the six WHO regions to be certified as poliomyelitis-free; the first was the Region of the Americas in 1994. WPR comprises 37 countries and territories (Figure 1) with an estimated 1.6 billion persons (27% of the world's population). PMID- 11215788 TI - Progress in development of immunization registries--United States, 2000. AB - Immunization registries are confidential, population-based, computerized information systems that attempt to collect vaccination data about all children within a geographic area. Registries are an important tool to increase and sustain high vaccination coverage by consolidating vaccination records of children from multiple providers, generating reminder and recall vaccination notices for each child, and providing official vaccination forms and vaccination coverage assessments. One of the national health objectives for 2010 is to increase to 95% the proportion of children aged <6 years who participate in fully operational population-based immunization registries (objective 14.26). To assess the status of immunization registry development, CDC analyzed self-reported data from 62 immunization grantees on the basis of data from the 2000 Immunization Registry Annual Report (IRAR). This report summarizes the results of this analysis, which indicate that approximately half of the grantees are operating population-based immunization registries that target their entire catchment areas; however, approximately 75% of children aged <6 years still need to be included in an immunization registry to reach the national health objective. PMID- 11215789 TI - Recommended childhood immunization schedule--United States, 2001. AB - Each year, CDC's Advisory Committee on Immunization Practices (ACIP) reviews the recommended childhood immunization schedule to ensure that it remains current with changes in manufacturers' vaccine formulations, revisions in recommendations for the use of licensed vaccines, and recommendations for newly licensed vaccines. This report presents the recommended childhood immunization schedule for 2001 (Figure 1) and documents the changes that have occurred since the January 2000 publication. PMID- 11215790 TI - Association of surfactants and polymers studied by luminescence techniques. AB - Light emission spectroscopy has unique possibilities for the study of central issues of surfactants and associating polymers. With the help of luminescent probes, information may be obtained on matters such as molecular association, microstructure, and molecular dynamics; this constitutes an important contribution to the understanding and control of macroscopic properties, as well as biological function and technical applications. Important aspects of these systems considered in this review are: formation of micelles and hydrophobic microdomains; aggregation numbers of surfactants; shape of molecular aggregates; size of droplets in water or in oil in microemulsions; formation and stability of vesicles; intra- vs. intermolecular association in polymers; conformational changes in polymers; polymer-surfactant association; surfactant organization in adsorbed layers; kinetic aspects regarding the formation and disintegration of self-assembly structures; residence times of molecules in microdomains and migration of active molecules. PMID- 11215791 TI - Diffusing probe measurements in Newtonian and elastic solutions. AB - The diffusion coefficients of polystyrene latex spheres and hematite particles in both Newtonian and elastic liquids have been measured using dynamic light scattering. The diffusion coefficients of the latex particles measured in glycerol/water (Newtonian) solutions obey Stokes-Einstein behaviour over a range of solvent viscosities and temperatures. Two apparent diffusion coefficients for the particles are measured in visco-elastic polyacrylamide and polyacrylate solutions and are designated Dfast and Dslow. The apparent fast diffusion coefficients measured in the elastic solutions show an increase to a maximum, above that measured in the solvent water, with increasing polyelectrolyte concentration. At higher polyelectrolyte concentrations the observed Dfast values decrease below the value obtained in the solvent water. Dfast increases with the scattering vector squared (q2) while Dslow, is independent of q2. PMID- 11215792 TI - Supra-aggregates. AB - Mixtures of oil (isooctane), water, and a double-chained ionic surfactant, Cu(AOT)2 [copper(II) bis(2-ethylhexyl)sulfosuccinate] form equilibrium phases consisting of spontaneous emulsions thermodynamically stable systems. The experimental conditions are such that the head polar group of the surfactant is totally hydrated. The emulsion droplets are comprised of supra aggregates, lamellar spherulites in which interior and exterior are bicontinuous microemulsions. The microstructures and component ratios can be predicted from elementary considerations that require only the notion of local and global packing constraints. The phenomenon of supra aggregation, microphases within any topologically closed container, in equilibrium with an external phase, appears quite general. The results throw some light on the meaning of 'phase' in mesostructured fluids. PMID- 11215793 TI - Aggregation numbers and microstructure characterization of self-assembled aggregates of poly(ethylene oxide) surfactants and related block-copolymers, studied by spectroscopic methods. AB - This review presents typical examples of micellar size measurements and structural characterization of self-assembled systems as determined with spectroscopic methods, selected from our representative results accumulated in recent years of systematic studies. The choice of examples has aimed at emphasizing the potentiality of the methods used in the study of poly(ethylene oxide) (PEO) surfactants. By using the time-resolved fluorescence quenching method aggregation numbers have been determined for direct and reverse micelles as well as for micelle-like clusters formed in (bio)polymer-surfactant solutions. By using specific spectral parameters of a variety of properly chosen molecular probes [fluorescence, UV-VIS and electron spin resonance (ESR) spin probes], problems such as hydration degree and profile of the PEO chains, local viscosity, ordering and packing of surfactant chains have been addressed. The intention was to correlate results obtained from different spectroscopic methods and to refer all polarity data to a common scale, such as Kosower's polarity factor. PMID- 11215794 TI - Various aspects of the constraints imposed on the photochemistry of systems in porous silica. AB - This manuscript briefly reviews the photochemistry of organic molecules on porous silica (or SiO2). To gain an understanding of the chemistry on silica, data are displayed and discussed with respect to studies in homogeneous solution. In particular, the exact dimensionality of kinetic processes on porous SiO2 is a matter for debate. Hence, units of concentration of an adsorbate on the surface are expressed as moles per nanometer squared and as moles per liter, in order to compare with solution. Many studies show that organic molecules adsorb to SiO2 via the surface silanol (or surface hydroxyl OH) groups. The adsorption is heterogeneous, due to various clusters of silanol groups and to charge transfer (CT) sites. Photophysical studies clearly show these effects. The photo-induced reactions on SiO2 may be described by 'fractal' approaches, but a 'Gaussian' approach is often more useful to the photochemist. Photo-induced reactions occur via movement of the reactants on the surface, as in the case of the Langmuir Hinshelwood (LH) mechanism or, as in the case of the Eley-Rideal (ER) mechanism, by bombardment of a surface bound excited state by a gaseous reactant, such as O2. Quenching of excited singlet states by O2 produces excited triplet states, which in turn are quenched to give singlet molecular oxygen. At room temperature the O2 quenching process on silica occurs by both mechanisms to approximately the same extent. However, the LH mechanism is dominant at lower temperatures and the ER mechanism is dominant at higher temperatures. Some quenchers, including carbon tetrachloride and tetranitromethane only quench by the LH mechanism giving rise to static quenching and chloro or nitro derivatives of the excited state. Photo induced electron transfer between excited arenes and amines occurs readily, but the ionic products are short-lived compared to solution. This is due to the limited diffusion of the products on the surface, which in turn promotes back electron transfer. Photoionization of arenes occurs on SiO2 via a two-photon process and gives very long-lived ions compared to solution. This is due to trapping of the photo-produced electrons by the SiO2 itself. Finally, the effects of co-adsorbants, including solvents, surfactants, and polymers, in photoreactions at the SiO2 surface are considered. The review ends with suggestions for future studies. PMID- 11215795 TI - Phase diagrams of systems with cationic alpha-helical membrane-spanning model peptides and dioleoylphosphatidylcholine. AB - Ternary phase diagrams have been constructed of systems with dioleoylphosphatidylcholine (DOPC) and water, and two alpha-helical membrane spanning model peptides, KKLAKK16[KK(LA)6KK] and KKLAKK20[KK(LA)8KK]. It was found that these peptides induced non-lamellar liquid crystalline phases. The amount of peptide needed for this phase transition depended on the water content and the temperature; and for KKLAKK16, a smaller amount of peptide was needed to induce non-lamellar phases than for KKLAKK20. Both peptides were found to induce an isotropic phase, and KKLAKK16 also induced a reversed hexagonal phase. Both peptides may also reside in a lamellar (L(alpha)) phase. When magic angle spinning (MAS) 31P NMR experiments were performed on samples containing the L(alpha) phase and an isotropic phase, four different isotropic chemical shifts were observed. The isotropic chemical shifts could be assigned to the phases, using spinning sidebands to calculate the chemical shift anisotropy (CSA) corresponding to each isotropic shift. MAS 13C NMR also indicated a difference in the aggregational state of the peptides between the L(alpha) and isotropic phases. The phase diagrams were compared to the phase diagram of a similar model peptide, AWW(LA)5WWA in systems with DOPC and water. It was concluded that the phase behaviour was influenced by both electrostatic interactions between the peptides and the lipid headgroups, and the difference between the hydrophobic length of the peptide and the hydrophobic thickness of the lipid bilayer. PMID- 11215796 TI - Solute exchange between surfactant micelles by micelle fragmentation and fusion. AB - Stopped-flow time-scan experiments on both Triton X-100 (TX100) micelle and sodium dodecylsulfate (SDS) micelles, with the pyrene-containing triglyceride 1 as a probe, establish that there are two distinct solute exchange mechanisms with rates on the time scale of milliseconds to minutes. One process exhibits second order kinetics with a rate proportional to the concentration of empty micelles. For TX100 micelles, this process is rapid (k2 approximately 10(6) M(-1) s(-1) at 24.6 degrees C) and is characterized by an activation energy of 160 kJ mol(-1). From the fact that this rate is nearly independent of the structure of the probe we infer that the exchange involves micelle fusion to form a short-lived super micelle, followed by fragmentation to form two normal (or 'proper') micelles. The rate of the first-order process decreases as the size of the probe increases (1 octylpyrene > 1-dodecylpyrene > 1). For SDS, both rates are very sensitive to the salt (NaCl) concentration. All indications point to this exchange process involving rate-limiting fragmentation of the micelle into two sub-micelles, these in turn grow back to normal micelles by addition of surfactant monomers or by collision with other sub-micelles. We explain the dependence of this rate on the nature of the probe by suggesting that only sub-micelles of a certain size are capable of carrying the probe with them as they separate from the original micelle. PMID- 11215797 TI - The dipole potential of phospholipid membranes and methods for its detection. AB - The dipole potential is an electrical potential within phospholipid membranes, which arises because of the alignment of dipolar residues of the lipids and/or water dipoles in the region between the aqueous phases and the hydrocarbon-like interior of the membrane. For a fully saturated phosphatidylcholine membrane, its value is believed to be in the range 220-280 mV, positive in the membrane interior. This results in an enormous electric field strength within the membrane of 10(8)-10(9) Vm(-1). The dipole potential is thus likely to have great significance in controlling the conformation of ion-translocating membrane proteins and so in regulating enzyme function. Because of its location within the membrane, quantification of the dipole potential is extremely difficult and presents a great challenge to the experimentalist and theoretician alike. Both electrical and spectroscopic methods developed for the determination of the dipole potential on lipid bilayers and monolayers are presented and possible causes for differences in the values derived are discussed. PMID- 11215798 TI - Formation of vesicles in diluted aqueous solutions of surfactant investigated by direct analysis of light scattering. AB - Formation of aggregates in the binary systems of double-tailed surfactant, sodium 4-(1-pentylheptyl)benzenesulfonate, and water in the dilute regime was supposed to occur within 5.0-8.5% of surfactant concentration. The size of particles was determined by light scattering. In addition, the samples were observed at room temperature using an Axiovert 35 Zeiss polarized light microscope operated with differential interference contrast optics. The observed aggregates could, in theory, belong a vesicle phase. All the histograms obtained by light scattering showed a bimodal distribution of particles. Weight factors including intensity, volume and number distribution indicate 97-100% of small aggregate sizes, since the peaks for the big sizes indicate only a small number of the aggregate population. Small aggregates have shown monodispersity with diameters of the aqueous core amounting to 38.94 and 54.94 nm relating to the surfactant concentration of 6.0 and 8.0%, respectively. Hydrodynamic radii determined by the Cumulant method, by the inverse Laplace transformation, and using a plot 1/tau vs. q2, showed values within the usual precision limits. PMID- 11215799 TI - The surface pressure effect of pentaoxyethylene and maltoside surfactant head groups. AB - From experimental surface tension data for water solutions of dodecyl-beta maltoside, C12M, and dodecyl-penta-(ethylene oxide), C12EO5, in the range below the CMC, the corresponding head group surface pressure functions vs. packing density were derived. These functions were compared with theoretical expressions based on some different models of the mixed head group/water film. Tentatively, we concluded that the two-dimensional hard fluid approach provides a convenient starting-point in order to account for the observed surface pressures of both the maltoside and EO head groups. PMID- 11215800 TI - Enzymatic degradation of polymer covered SOPC-liposomes in relation to drug delivery. AB - Polyethylenoxide (PEG) covered liposomes are used as lipid-based drug-delivery systems. In comparison to conventional liposomes the polymer-covered liposomes display a long circulation half-life in the blood stream. We investigate the influence of polyethyleneoxide-distearoylphosphatidylethanolamine (DSPE-PEG750) lipopolymer concentration on phospholipase A2 (PLA2) catalyzed hydrolysis of liposomes composed of stearoyloleoylphosphatidylcholine (SOPC). The characteristic PLA2 lag-time was determined by fluorescence and the degree of lipid hydrolysis was followed by HPLC analysis. Particle size and zeta-potential were measured as a function of DSPE-PEG750 lipopolymer concentration. A significant decrease in the lag-time, and hence an increase in enzyme activity, was observed with increasing concentrations of the anionic DSPE-PEG750 lipopolymer lipids. The observed decrease in lag-time might be related to changes in the surface potential and the PLA2 lipid membrane affinity. PMID- 11215801 TI - Transformation of phospholipid membranes by thiyl radicals via cis-trans isomerization of fatty acid residues. AB - Thiyl radical-mediated transformation of unsaturated fatty acid residues are reported. Beside the initiation of lipid peroxidation, thiyl radicals can efficiently cause isomerization of fatty acid residues in a catalytic manner. The latter process is observed in homogeneous solutions as well as in organized assemblies, leading to a denaturation of the natural all-cis-isomers of fatty acid residues of lipid bilayers. The degree of denaturation goes parallel with an increase in the number of double bonds and in the hydrophobicity of thiols. For arachidonic acid methyl ester, a decay of the all-cis-isomer to approximately 30% after a gamma irradiation dose of 1.8 kGy in micelles is observed. The reversibility of the isomerization reaction is demonstrated in liposomes by the fact that the cis/trans-equilibrium is independent of configuration of the starting compound. PMID- 11215802 TI - Mats Almgren and colloid chemistry. AB - His sixtieth birthday provides an opportunity to describe Mats Almgren's impact on colloid chemistry. PMID- 11215803 TI - Spontaneous vesiculation. AB - The thermodynamics of vesicle formation was analyzed by using the elastic bending energy approach. Several different possibilities of spontaneous vesiculation, due to soft bilayers, non-zero spontaneous curvature and Gaussian curvature, respectively, were presented and discussed. Intermediate structures in the closed vesicle-disklike mixed micelle phase transition could be either cup-like particles or open bilayers partially rolled into lipid tubules. PMID- 11215804 TI - Modification of the lyotropic liquid crystalline microstructure of amphiphilic block copolymers in the presence of cosolvents. AB - This article reviews the results of recent investigations on the macroscopic (phase behavior) and microscopic (microstructure) aspects of the role of cosolvents on the self-assembly of amphiphilic copolymers. A comprehensive account of the systematic studies performed in ternary isothermal systems consisting of a representative poly(ethylene oxide)-poly(propylene oxide) poly(ethylene oxide) (PEO-PPO-PEO) block copolymer (Pluronic P105, EO37PO58EO37), water and a polar cosolvent (such as glycerol, propylene glycol or ethanol) is presented. The effect of cosolvents on the copolymer phase behavior is quantified in terms of the highest cosolvent/water ratio able to maintain the liquid crystalline structures. The effect of cosolvents on the microstructure of the lyotropic liquid crystals is quantified in terms of the degree of relative swelling per cosolvent content per copolymer content, a parameter that characterizes the given cosolvent and copolymer. The set of correlations on the cosolvent effects on the phase behavior or microstructure to the cosolvent physicochemical characteristics (such as octanol/water partition coefficient or solubility parameter) have led to the development of a hypothesis that accounts for the cosolvent effects on the self-assembly of PEO-PPO-PEO block copolymers and can be used to predict them. The rich structural diversity and the potential for a precise an convenient modification of the lyotropic liquid crystalline microstructure of the PEO-PPO-PEO block copolymers is discussed in comparison to the phase behavior of the low-molecular nonionic surfactants. PMID- 11215805 TI - Adsorption of liposomes and emulsions studied with a quartz crystal microbalance. AB - The adsorption from phospholipid liposome solutions (1.2%) and phospholipid stabilized oil-in-water emulsions (20% purified soybean oil) with the same phospholipid liposome concentration, has been followed by means of a quartz crystal microbalance allowing the simultaneous determination of changes in resonance frequency and energy dissipation. Both the fundamental resonance frequency and the third overtone were used for following the interfacial processes. The adsorption from the liposome solution resulted in formation of a phospholipid bilayer with an additional and incomplete outer layer of liposomes. The outer layer was removed by dilution leaving a bilayer of phospholipids on the surface. The adsorption process observed from the concentrated emulsion solution was considerably more complex. A slow spreading process that also resulted in some expulsion of material from the interface followed the rapid initial adsorption of emulsion droplets. After rinsing with water a phospholipid bilayer was retained on the surface. PMID- 11215806 TI - On the formation of concentrated stable w/o emulsions. AB - The conditions for the formation of concentrated w/o emulsions based on Aerosol OT and aliphatic hydrocarbons were studied. It was found that high stability is obtained if the attraction between the emulsion droplets is kept to a minimum. This is achieved by matching the refractive index of the dispersed phase and the organic phase. Furthermore, it is shown that the mere presence of salt does not render any stability. Hence, the speculated mechanism that salt stabilises against Ostwald ripening does not hold for these emulsions. PMID- 11215807 TI - Ultrasonic shear wave rheology of weak particle gels. AB - Weak particle gels have attracted increasing attention in the last decade. These gels have a very short region of deformation over which their viscoelastic parameters are constant. They can be broken easily in response to external forces. Therefore the rheological measurements in these systems must be performed at very small deformations, which may frequently be below the accuracy limits of conventional rheological instruments. In the present paper we discuss the application of the thickness shear mode resonator technique for the measurement of viscoelastic parameters of weak particle gels in the MHz frequency range. The technique provides information on the viscoelasticity of weak gels in the time scale 10(-7)-10(-9) s. The length scale of the measurements, determined by the depth of penetration and the wavelength of the shear wave, falls in the submicron and micron range. The displacements in the shear deformations generated in this technique are extremely small, in the order of Angstroms, and the shear strain, approximately 10(-3), corresponds to the low limits in the classical dynamic rheology measurements. Only small volumes, down to 0.1 ml, of sample are required and this is another advantage of this technique. The measurements of the storage, G', and the loss, G'', moduli can be carried out non-invasively and continuously at various frequencies in the same sample during the whole length of the process of gelation. General and specific aspects of the measurements and interpretation of experimental results are discussed in the present paper. PMID- 11215808 TI - The effect of surface active solutes on bubbles exposed to ultrasound. AB - A review of the effects of a range of surface active solutes, aliphatic alcohols, alkyl amines, carboxylic acids and surfactants on bubbles exposed to ultrasound is presented. The solutes are shown to affect the phenomenon of sonoluminescence (SL) in quite a number of different ways. Ionic surfactants have a strong influence on interbubble interactions which at low concentrations (1 mM) results in an enhancement in SL. Alcohols and the neutral forms of the organic acids and amines induce SL quenching. The SL quenching is attributed to the formation and accumulation of decomposition products in the hot core of an oscillating bubble resulting from the evaporation of volatile solute adsorbed at the bubble interface. Some results are presented on the influence of low concentrations of alcohol on the SL generated from a single bubble and on the bubble dynamics, when exposed to ultrasound. These results add support to the interpretation given for solute-induced effects observed in multibubble systems. It is also shown that SL can be used as an internal light source to excite aromatic solutes that subsequently fluoresce, a process referred to as sonophotoluminescence. PMID- 11215809 TI - Synthesis, characterization and potential applications of new materials in the mesoporous range. AB - M41S is the designation of a new type of mesoporous structures. The characteristics of these materials are large surface areas and very narrow pore size distributions, with pore diameters tunable from 15 to 100 A. The M41S family consists of MCM-48, which has a cubic ordered pore structure, MCM-41, which has a hexagonally ordered pore structure and MCM-50, which has an unstable lamellar structure. In this review we cover the synthesis, modification, characterization and potential applications of these materials. PMID- 11215810 TI - Polyelectrolyte and surfactant mixed solutions. behavior at surfaces and in thin films. AB - Dilute mixed solutions of non-surface active anionic polymers (polyacrylamide and polystyrene sulfonate, xanthan) and various surfactants have been studied with several methods: surface tension, ellipsometry, X-ray and neutron reflectivity, thin film balance, surface and bulk rheology. A strong synergistic lowering of the surface tension is found with cationic surfactants in the concentration range where no appreciable complexation of surfactant and polymer occurs in the bulk solution (as seen from viscosity measurements). Despite appreciable differences between surface tension behaviour, the adsorbed layer is very similar for all the polymers: their thickness is small and the polymer chains are stretched along the surface. The surface tension behaviour of these polymers with non-ionic surfactants is also different. When the polymers are confined in thin films, the forces between surfaces are similar, and independent of surfactant nature: oscillatory forces are measured, which reflect the existence of a polymer network with a well defined mesh size. The connection of foam stability with surface and bulk complexation is far from clear. PMID- 11215811 TI - Kinetics of diffusion-assisted reactions in microheterogeneous systems. AB - This review is focused on the basic theory of diffusion-assisted reactions in microheterogeneous systems, from porous solids to self-organized colloids and biomolecules. Rich kinetic behaviors observed experimentally are explained in a unified fashion using simple concepts of competing distance and time scales of the reaction and the embedding structure. We mainly consider pseudo-first-order reactions, such as luminescence quenching, described by the Smoluchowski type of equation for the reactant pair distribution function with a sink term defined by the reaction mechanism. Microheterogeneity can affect the microscopic rate constant. It also enters the evolution equation through various spatial constraints leading to complicated boundary conditions and, possibly, to the reduction of dimensionality of the diffusion space. The reaction coordinate and diffusive motion along this coordinate are understood in a general way, depending on the problem at hand. Thus, the evolution operator can describe translational and rotational diffusion of molecules in a usual sense, it can be a discrete random walk operator when dealing with hopping of adsorbates in solids, or it can correspond to conformational fluctuations in proteins. Mathematical formulation is universal but physical consequences can be different. Understanding the principal features of reaction kinetics in microheterogeneous systems enables one to extract important structural and dynamical information about the host environments by analyzing suitably designed experiments, it helps building effective strategies for computer simulations, and ultimately opens possibilities for designing systems with controllable reactivity properties. PMID- 11215812 TI - Applications and limitations of uranyl ion as a photophysical probe. AB - Uranyl ion has a long-lived luminescent excited state, which can be used as a probe for the aggregation behaviour in a variety of surfactant and polymeric systems. The general spectroscopy and photophysics of this species are discussed, and the applications to specific micellar, microemulsion, vesicular and liquid crystalline systems presented. It is shown that both dynamic and structural information can be obtained from spectral and kinetic data. Examples of applications of uranyl probe studies to technologically important mesoscopic and mesoporous systems involving metal oxides, or their salts, and to humic acids and soils will also be reviewed. Emphasis will be given to both the advantages and restrictions on the use of this useful photophysical probe. PMID- 11215813 TI - Gross cystic disease fluid protein (GCDFP-15) in the breast: past and present. PMID- 11215814 TI - Differential induction of the 200-family proteins in Daudi Burkitt's lymphoma cells by interferon-alpha. AB - Interferon (IFN)-inducible "effector" proteins mediate the biological activities of the IFNs. Therefore, the identification of the functional role(s) of IFN inducible proteins in IFN action is important to elucidate the molecular mechanisms by which IFNs inhibit cell growth. One family (the "200-family") of IFN-inducible proteins includes structurally related murine (p202a, p202b, p203, p204 and D3) and human (MNDA, IFI-16 and AIM2) proteins. However, their role in IFN action remains to be established. Here we report that IFN-alpha treatment of Daudi Burkitt's lymphoma cells resulted in differential induction of MNDA, IFI 16, and a p202-related protein (p202RP). Interestingly, IFN induction of p202RP preceded the induction of MNDA and IFI 16 proteins and the growth inhibition by IFN. Additionally, the induction of these proteins by IFN was accompanied by: (i) a transient increase in p21(WAF1/CIP1) levels; (ii) an increase in the functional form of pRb and p130; (iii) an inhibition of the sequence-specific DNA binding activity of E2F complexes; and (iv) a marked decrease in c-Myc levels. Our observations reported herein provide support to the hypothesis that IFN-inducible p202RP and MNDA proteins from the 200-family contribute to the growth inhibitory activities of the IFNs. PMID- 11215815 TI - TCR and immunophenotype changes in dimethyl sulfoxide-dependent programmed cell death. AB - In the thymus most deleted cells are immature thymocytes and the high rate of cell death within the thymus is involved in the development of the initial T-cell receptor repertoire. Functional T-cell receptor recognition units are created by somatic rearrangements of gene segments, and the expression of successfully assembled TCR complex is the key to molecular events that culminate in T-cell activation, growth and differentiation. Previously, we reported that DMSO induces apoptosis in RPMI-8402 human pre-T cells. Here we examine the fate of pre-T cells undergoing negative selection analysing the responsiveness to DMSO-enforced TCR expression and immunophenotype modulation. Our results demonstrate that DMSO induces cell growth inhibition, cell phenotype changes, with down-regulation of CD2 and CD7, and increases in alpha/beta or gamma/delta TCR chains led by TdT, RAG-1 and RAG-2 activity. These modifications are associated with an apoptotic program. Taken together, these data suggest the existence of an early checkpoint that ensures in vivo the effective intrathymic differentiation supported from another point of view, the linkage between immunophenotypes and TCR regulation in T-cell differentiation and programmed cell death. PMID- 11215816 TI - Serum concentrations of interleukin-18 in early and advanced cancer patients: enhanced secretion in metastatic disease. AB - The recent availability of adequate methods for cytokine measurement could contribute to better understanding the immunophysiopathology of neoplastic disease. Unfortunately, very little data is available about cytokine secretion in cancer patients. At present, IL-2, IL-12 and IL-15 represent the major antitumor cytokines in humans. Preliminary clinical studies have shown a progressive decline in IL-2 levels with cancer progression, whereas IL-12 seems to increase in the advanced disease. IL-18 is the latest cytokine discovered by potential anticancer and anti-angiogenetic activity, and it has effects similar to those of IL-12. This preliminary study was carried out to analyze IL-18 secretion in early or advanced cancer patients. The study included 40 cancer patients (lung cancer, 21; gastrointestinal tumors, 19), 17 of whom had metastatic disease, and 50 healthy controls. Serum levels of IL-18 were measured by ELISA. No significant difference in IL-18 mean levels was seen between controls and non-metastatic patients. In contrast, metastatic patients showed significantly higher IL-18 mean values with respect to both healthy controls and non-metastatic patients. This preliminary study seems to suggest that metastatic disease may be characterized by enhanced IL-18 secretion the biological and prognostic significance to be established by successive clinical investigation. PMID- 11215817 TI - B lymphocyte differentiation antigens. PMID- 11215818 TI - CD37. PMID- 11215819 TI - CDw75. PMID- 11215820 TI - CDw76. PMID- 11215821 TI - CD77. PMID- 11215822 TI - CD84. PMID- 11215823 TI - CD21. PMID- 11215824 TI - CD22. PMID- 11215825 TI - CD74. PMID- 11215827 TI - CD31. PMID- 11215828 TI - CD32 (Fc gammaRII). PMID- 11215829 TI - CD56. PMID- 11215830 TI - CD57. PMID- 11215831 TI - CD87. PMID- 11215832 TI - CD147. PMID- 11215833 TI - The AIDS drug assistance programs and coverage of HIV-related medications. AB - BACKGROUND: AIDS drug assistance programs (ADAPs) have been implemented in each state to facilitate access to medications for low-income, uninsured, and underinsured people with HIV disease. Policies for each ADAP differ, and these differences influence the access people with HIV have to medications. OBJECTIVE: To compare the coverage of medications and sources of program funding for the state ADAPs. DESIGN: A self-administered mailed survey, sent to administrators of the 50 state ADAPs and the District of Columbia ADAP in December 1998. RESULTS: Forty-nine of the 51 ADAPs (96%) responded to the survey. Title II of the Ryan White Comprehensive AIDS Resources Emergency Act provided a large majority of the funding for the ADAPs, with a number of states also using state funds and/or Title I funds for their programs. The formularies of all ADAPs were nearly identical with respect to coverage of antiretrovirals, but differed in the number and types of other medications included. Some states limited access to medications through waiting lists, enrollment caps, and other policies. Sixteen ADAPs reported that the coverage of protease inhibitors resulted in an appropriation of state government funds to their ADAP, while eight states reported an ADAP budget shortfall. In general, ADAPs in poorer and more rural states included a fewer number of medications on their formularies. CONCLUSIONS: Access to antiretrovirals and other medications is available through state ADAPs, but may be limited in some states due to waiting lists, controls on the enrollment of new beneficiaries, and policies on the number and types of medications beneficiaries may receive. PMID- 11215834 TI - The relationship between preadmission indicators and basic math skills at a new school of pharmacy. AB - OBJECTIVE: To examine the relationship between preadmission indicators of 49 PharmD students entering their first professional year at a new school of pharmacy and their scores on a Basic Math Skills Test (BMST). A secondary objective was to determine what factors, if any, contributed to the successful completion of the BMST. METHODS: This cross-sectional investigation used a convenience sample of PharmD students entering the first professional year at a three-year-old, private, southeastern school of pharmacy. All first-year students who took the mandatory BMST, as part of a math mentor plot program, were eligible for enrollment. The BMST covered nine different competencies and was validated at the grade-8 level. Math test scores, the student's Pharmacy College Admissions Test (PCAT), and other demographic and scholastic information was obtained from the student's application file in a retrospective manner. All identifiers were removed before the data were submitted to the investigators. RESULTS: Statistical analysis suggested that two preadmission indicators strongly influenced BMST performance: percentile scores on the quantitative section of the PCAT (POAT-OP) and whether the student attended a private or public university prior to admission to the pharmacy school. In addition, four factors significantiy contributed to successful completion of the BMST: math/science grade point average (MS-GPA), PCAT percentile scores, PCAT-QP percentile scores, and the number of BMST Items left blank. CONCLUSIONS: A relationship exists between preadmission indicators of PharmD students entering their first professional year and their BMST score. In addition, certain identifiable factors impact BMST scores of first-year PharmD students. Admissions committees may find this useful in identifying students who may need remedial math assistance prior to beginning math-intensive courses such as pharmaceutical calculations and pharmacokinetics. PMID- 11215835 TI - Topiramate titration and tolerability. AB - OBJECTIVE: To evaluate the tolerability and efficacy of two titration rates for topiramate initiated as adjunctive therapy in adults with partial-onset seizures, with or without secondary generalization, in a multicenter, double-blindtrial. METHODS: After a two-week baseline phase, 188 patients were randomized to either a 50/50 titration schedule (initial dosage 50 mg/d increased in 50-mg/d increments at weekly intervals; n = 95) or to a 100/200 titration schedule (initial dosage 100 mg/d increased by 100-200 mg/d at weekly intervals; n = 93). The maximum dosage of 400 mg/d was therefore achieved in eight weeks or three weeks, respectively. RESULTS: Compared with the 100/200 titration rate, the 50/50 titration rate significantly reduced the cumulative incidence of treatment emergent adverse events (TEAEs) leading to changes in topiramate therapy (ie., dosage reductions, interruptions or discontinuations of therapy) (p = 0.048) and significantly reduced treatment interruptions or withdrawals due to TEAEs (p = 0.040). Mild or moderate effects involving the central nervous system were the most frequent adverse events. At the final visit, therapeutic responses were comparable in the 50/50 and 100/200 titration groups: median percent seizure reduction was 42% vs. 33%, proportion of patients with 250% seizure reduction was 42% vs. 38%, and proportion of patients with no seizures during double-blind treatment was 14% vs. 10%, respectively. Seizure frequency was substantially reduced from baseline during topiramate titration. At day 22, with the 50/50 titration group receiving 150 mg/d and the 100/200 titration group receiving 400 mg/d, the mean percent seizure reduction was 51% and 54%, respectively. CONCLUSIONS: Gradual initiation of topiramate therapy can significantly enhance patient tolerability without delaying therapeutic response. PMID- 11215836 TI - Possible serotonin syndrome associated with clomipramine after withdrawal of clozapine. AB - OBJECTIVE: To report on the possible development of serotonin syndrome in a patient receiving clomipramine after clozapine was withdrawn from the treatment regimen. CASE REPORT: A 44-year-old white man with a 23-year history of undifferentiated schizophrenia and obsessive-compulsive behavior had been treated with clozapine and clomipramine for several years. He tolerated both agents together well, with the exception of experiencing chronic constipation. Clomipramine was tapered and reduced to 50 mg over a period of 10 days. A worsening of ritualistic behavior was noted, and the clomipramine dosage was increased to 150 mg/d over 14 days. Simultaneously with the clomipramine dosage increase, clozapine was tapered and stopped ever a period of 19 days. The day after clozapine was stopped, while he was still receiving clomipramine 150 mg/d, he began behaving oddly, started sweating profusely, shivering, and became tremulous, agitated, and confused. He was diagnosed with possible serotonin syndrome; his symptoms resolved after clomipramine was stopped but before clozapine was restarted eight days later. DISCUSSION: There are similarities in symptoms between serotonin syndrome and clozapine withdrawal. This article discusses the reasons why this case may represent serotonin syndrome rather than clozapine withdrawal and the possible pharmacologic mechanisms involved. CONCLUSIONS: Clinicians should be aware that removing a serotonin-2a (S-HT2a) antagonist 1mm a treatment regimen including an agent that increases serotonin in the synaptic cleft may worsen clozapine withdrawal or potentially result in serious adverse drug reactions, such as serotonin syndrome. PMID- 11215837 TI - Subtherapeutic INR values associated with a switch to generic warfarin. AB - OBJECTIVE: To discuss the effect on the international normalized ratio (INR) when patients are converted from therapy with Coumadin to generic warfarin. CASE SUMMARY: Two cases at a family medicine center anticoagulation clinic in Oklahoma City, OK, in which subtherapeutic INR values occurred after a switch from Coumadin to generic warfarin, while all other variables were kept consistent demonstrate the need for close monitoring of the INR when patients are switched between brands of warfarin. DISCUSSION: Warfarin is a narrow therapeutic index drug since small changes in systemic concentration can lead to significant variation in phamacodynamic response. In March 1997, the Food and Drug Administration (FDA) approved generic warfare based on the FDA and United States Pharmacopoeia (USP) standards. Due to different specifications between Dupont Pharma and the USP, content uniformity may differ between brand and generic forms of warfarin. United studies have demonstrated bioequivalence between brand and generic. The two cases presented demonstrate the potential for fluctuations in the INR when switching between generic and brand. Thus, these eases illustrate the need for close monitoring if a change is made. CONCLUSIONS: While considered bioequivalent by the FDA, switching between Coumadin and generic warfarin may lead to significant changes in the INR, warranting dose alterations due to different content uniformity specifications between Dupont Pharma and the USP. Patients switching between Coumadin and generic warfarin should have their INR monitored more carefully. PMID- 11215838 TI - Anticoagulation therapy for radiation-induced myelopathy. AB - OBJECTIVE: To report the use of heparin and enoxaparin for radiation-induced myelopathy. CASE SUMMARY: A 48-year-old White woman with presumed metastatic lung cancer presented with worsening numbness and weakness of both legs. The neuro oncology service was consulted and determined that the symptoms were consistent with radiation-induced myelopathy. The patient briefly responded to steroid treatment. A trial of intravenous heparin therapy was initiated by the primary team and managed by the clinical pharmacy services. Her symptoms improved when heparin was begun. She was able to walk and was subsequently discharged home on enoxaparin. DISCUSSION: Spinal cord injury is one of the known adverse effects of radiation. The onset of symptoms can be acute or delayed. The clinical signs and symptoms of delayed neurologic injury are related to the narrowing and occlusion of the vessel lumen, ischemia, edema, and cell death in the surrounding nervous tissue. Treatment often consists of corticosteroids and/or hyperbaric oxygen; however, the outcomes are often disappointing. In addition to the inhibition of serum protein-mediated coagulation, heparin inactivates or prevents the release of mediators of vascular injury inflammation, permeability, and edema. Therefore, patients with radiation-induced spinal cord injury may benefit from anticoagulant therapy. CONCLUSIONS: Heparin and/or enoxaparin may be considered as potential treatments for patients with radiation-induced myelopathy. PMID- 11215839 TI - Probable colchicine-induced neutropenia not related to intentional overdose. AB - OBJECTIVE: To report a case of neutropenia caused by colchicine not associated with intentional overdose or with preceding severe gastrointestinal symptoms. CASE SUMMARY: A 68-year-old white man was admitted to the hospital with intractable pain from an acute attack of gout. The patient was treated with standard doses of oral colchicine for several days. He experienced mild loose stools, but no severe diarrhea or nausea during treatment. The patient then developed severe neutropenia, with an absolute neutrophil count of 240 cells/mm3. His white blood cell count returned to normal after discontinuing colchicine and administering filgrastim. DISCUSSION: Although colchicine is commonly associated with neutropenia in cases of intentional or accidental overdose, the patient developed this adverse effect after being treated with doses commonly used for the acute treatment of gout. In addition, this patient had taken low-dose colchicine for many years without experiencing hematologic adverse effects. CONCLUSIONS: Colchicine is often an attractive alternative to nonsteroidal antiinflammatory agents for the treatment of gout, especially in patients at risk for renal impairment or gastropathy. Our case illustrates that colchicine treatment can cause hematologic adverse effects; the clinician should monitor cell counts in patients receiving this agent, especially at the higher doses used for acute treatment of gout. PMID- 11215840 TI - Idiopathic pneumonia syndrome following myeloablative chemotherapy and autologous transplantation. AB - OBJECTIVE: To report the outcome as well as the clinical, radiographic, and pathologic features of idiopathic pneumonia syndrome (IPS) following autologous peripheral blood stem cell transplantation (aPBSCT). CLINICAL FINDINGS: A total of 271 patients with a variety of underlying malignancies received busulfan containing myeloablative chemotherapy prior to aPBSCT; none of these patients received total body irradiation. Ten individuals developed IPS, with a median time of onset of 102 days after stem cell infusion. The major clinical and radiographic findings included an acute or subacute onset of dyspnea, cough, hypoxemia, and bilateral or unilateral infiltrates with or without pleural effusion. Pathologic findings consisted mainly of diffuse interstitial pneumonitis, organizing alveolitis, and cellular atypia. Nine patients diagnosed with IPS were treated with high doses of glucocorticoids parenterally. Despite heroic measures, eight patients died of IPS. The two remaining individuals recovered without experiencing significant long-term pulmonary sequelae. DISCUSSION: Chronic low-dose busulfan therapy results in lung injury in 4-6% of patients after several years of treatment and once the cumulative dosage begins to approach 3g. High-dose, short-course busulfan (16 mg/kg)-containing conditioning chemotherapy prior to aPBSCT can also be complicated by IPS. IPS differs from lung damage due to chronic busulfan therapy by its earlier onset, an acute or subacute rather than indolent presentation, characteristic clinical and radiographic features, and lack of multinucleated giant cells on pathologic review. The pathophysiology of IPS secondary to high-dose busulfan-containing myeloablative regimens is not known, but cell-mediated immune reactions and release of cytokines may contribute to the lung injury. Mortality is high (80%) despite the use of heroic measures, including mechanical ventilation. Some patients, however, can respond to high doses of parenteral corticosteroid therapy. CONCLUSIONS: IPS following high-dose, short-course busulfan-containing regimens exhibits unique clinical, radiographic, and pathologic features that differ from lung damage characteristic of chronic, low-dose busulfan therapy. Mortality from this complication is 80%, but some patients survive without long term pulmonary sequelae following early treatment with glucocorticoids. PMID- 11215841 TI - Successful use of donepezil for the treatment of dementia with Lewy bodies. AB - OBJECTIVE: To report a case of the successful use of donepezil for treatment of cognitive and noncognitive symptoms in a patient with dementia with Lewy bodies. CASE SUMARY: An 86-year-old white woman with dementia was experiencing early onset significant fluctuation of her cognitive status, functional impairment, visual hallucinations, aggression, and parkinsonism. She was intially diagnosed with Alzheimer disease and Parkinsons disease and prescribed donepezil 5 mg/d and benztropine 1 mg twice daily. On reexamination of the case by a neurologist, the diagnoses were revised to dementia with Lewy bodies. The benztropine was discontinued, and donepezil was increased to 10 mg/d. The patient's cognitive and functional status significantly improved, as did her visual hallucinations. DISCUSSION: This case supports previous reports of the marked responsiveness of patients with dementia with Lewy bodies to acetylcholinesterase inhibitors. This may be explained by the marked cholinergic deficit observed in patients with dementia with Lewy bodies and the evidence linking cognitive as well as noncognitive symptoms to this deficit. CONCLUSIONS: The present case suggests that patients with dementia with Lewy bodies respond well to acetylcholinesterase inhibitors. Controlled trials are necessary to further define the role of these drugs for this disease. PMID- 11215842 TI - Practice guidelines for lipid-based amphotericin B in stem cell transplant recipients. AB - OBJECTIVE: To provide clinicians who practice in the stem cell transplantation (SCT) setting with practical guidelines for the use of lipid-based amphotericin B (AmB) formulations in SCT patients who have documented or probable invasive fungal infections, are experiencing neutropenic fever, or require secondary prophylaxis for fungal infections. DATA SOURCES: Recommendations are based on the results of a two-day consensus meeting that convened clinicians versed in the management of infectious complications in patients undergoing SCT. This meeting, which was held October 21-23, 1998, in Orlando, Florida, was sponsored by an educational grant from The Liposome Company. In addition, primary articles were identified by MEDLINE search (1980-December 1999) and through secondary sources. STUDY SELECTION AND DATA EXTRACTION: All of the articles identified from the data sources were evaluated, and all information deemed relevant was included in this review. DATA SYNTHESIS: Immunocompromised patients, particularly patients undergoing high-dose chemotherapy with SCT, experience a high degree of morbidity and mortality from invasive fungal infections. Historically, treatment for such infections with conventional AmB had been limited primarily by its associated nephrotoxicity. Lipid-based formulations of AmB have helped to advance the management of invasive fungal infections in the SCT population by offering a treatment alternative that allows for administration of adequate amounts of active drug to produce clinical and mycologic responses, compared with conventional AmB, in a delivery system that is less nephrotoxic. Unfortunately, these agents are relatively expensive. Therefore, patients who are candidates for lipid-based products must be selected carefully. CONCLUSIONS: Practical guidelines are provided for the use of lipid-based AmB formulations in SCT patients who have documented or probable invasive fungal infections, are experiencing neutropenic fever, or require secondary prophylaxis for fungal infections. PMID- 11215843 TI - Fluorouracil and the new oral fluorinated pyrimidines. AB - OBJECTIVE: To briefly review the biotransformation and bioavailability of fluorouracil (5-FU); discuss the effects of dihydropyrimidine dehydrogenase (DpD) on the efficacy and toxicity profiles of 5-FU; and review a new class of drugs known collectively as the oral fluorinated pyrimidines, which inhibit or circumvent DpD activity and, when administered with 5-FU, alter its pharmacokinetic and pharmacodynamic properties. DATA SOURCES: A MEDLINE literature search was conducted (1966-March 1999) using the search terms fluoropyrimidines, fluorouracil, 5-FU, fluorinated pyrimidines, capecitabine, eniluracil, uracil-tegafur, uracil-ftorafur, UFT, S1, BMS-247616, and BOF-A2. Reference lists, bibliographies of pertinent articles, and abstracts from the American Society of Clinical Oncology and the San Antonio Breast Cancer Symposium annual meetings were also identified and reviewed. Both preclinical and clinical literature were reviewed and analyzed. DATA SYNTHESIS: The new oral fluorinated pyrimidines appear to produce antitumor activity equivalent or superior to that of intravenously administered 5-FU by achieving higher intratumoral 5-FU concentrations or sustained 5-FU exposure. These agents are generally associated with manageable and non-life-threatening toxicities. The oral route of administration facilitates ease of administration and may reduce total healthcare costs associated with 5-FU-sensitive tumors. More studies are needed to assess the therapeutic and economic benefits of the oral fluorinated pyrimidines. CONCLUSIONS: The bioavailability, efficacy, and toxicity of 5-FU depend on its catabolic rate-limiting enzyme, The new oral fluorinated pyrimidines inhibit or circumvent DpD activity and, when combined with 5-FU, increase 5-FU's bioavailability and cytotoxic effects and decrease its toxicities. Results of Phase I and II studies in patients with a variety of malignancies suggest positive outcomes, including greater efficacy, less drug-related toxicity, lower costs related to drug administration, and greater patient convenience. PMID- 11215844 TI - Ping wei san, a Chinese medicine for gastrointestinal disorders. AB - OBJECTIVE: To describe the dilemma that American pharmacists face when their patient uses a traditional Chinese herbal formula. Ping wei san (PWS), an agent used to treat gastrointestinal disorders, is used to illustrate the problems encountered and to identify resources on Chinese herbal medicines available to pharmacists. DATA SYNTHESIS: In the US, Chinese herbal medicine is making its way into mainstream Western medicine. Patients may discover PWS in their search for a substitute for cisapride, which was partially withdrawn from the US market in July 2000. The pharmacist may be called on to assist in the management of patients who wish to use PWS for treatment of common gastrointestinal disorders like gastritis, esophageal reflux, gastric or duodenal ulcers, and acute or chronic enteritis. As with most other Chinese herbal formulas, English-language literature about PWS is limited and is often difficult to interpret. Pharmacists who are unfamiliar with the basic principles and terminology used in traditional Chinese medical practices will need to identify sources of information about this complementary alternative practice to be able to provide pharmaceutical care for patients taking a Chinese herbal formula like PWS. CONCLUSIONS: To develop a pharmaceutical care plan for patients using a Chinese herbal medicine therapy such as PWS, the pharmacist will need to become familiar with traditional Chinese medical practices and terminology describing indications, therapeutic effects, and risks. Fortunately, resources are available to pharmacists who need assistance in interpreting information on Chinese herbal therapies so that they can appropriately manage patients using them. PMID- 11215845 TI - Do HMG-CoA reductase inhibitors affect fibrinogen? AB - OBJECTIVE: To review commonly used fibrinogen assay methods and the evidence demonstrating an association between fibrinogen and increased risk of coronary artery disease and to review the current literature to determine and assess the impact of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on fibrinogen. DATA SOURCES: Primary and review articles identified from a MEDLINE search (1966-December 1999); references obtained from these publications were subsequently reviewed for additional relevant articles. STUDY SELECTION AND DATA EXTRACTION: All articles were evaluated, and all relevant information was included in this review. DATA SYNTHESIS: The Clauss method is currently the preferred method for determining plasma fibrinogen concentrations, due to its high degree of accuracy and precision. Furthermore, unlike immunologic methods, its reliability is unaffected by change in triglycerides. The effects of four HMG CoA reductase inhibitors (atorvastatin, lovastatin, simvastatin, pravastatin) on fibrinogen have been evaluated. Atorvastatin has been shown to induce significant increases in fibrinogen (22% increase; p <0.05) by using the immunonephelometric method. This method also demonstrated that lovastatin use was associated with a 24.4% increase (p < 0.0001) in plasma fibrinogen concentration. Simvastatin has been shown in multiple studies using the Clauss method to have a neutral effect on fibrinogen. The majority of studies have revealed significant decreases (7 19%) in fibrinogen following treatment with pravastatin. CONCLUSIONS: Future studies need to be performed evaluating the effects of HMG-CoA reductase inhibitors on fibrinogen, but using direct comparisons and clotting assay methodology. PMID- 11215846 TI - Combined therapy with an angiotensin II receptor blocker and an angiotensin converting enzyme inhibitor in heart failure. AB - OBJECTIVE: To evaluate the safety, tolerability, and efficacy of chronic combination therapy with an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II receptor blocker (ARB) in the management of heart failure. DATA SOURCES: Clinical literature was accessed through MEDLINE (January 1966-June 2000). Key search terms included angiotensin-converting enzyme inhibitor; losartan; combined modality therapy; drug effects; heart failure, congestive; and receptors, angiotensin. DATA SYNTHESIS: Heart failure is widely prevalent and continues to be associated with high morbidity and mortality, even with currently recommended care. At the moderate doses studied for patients with mild heart failure in brief trials, combined ACE inhibitor and ARB therapy was well tolerated and had an additive effect in reducing blood pressure and relieving symptoms of heart failure. CONCLUSIONS: An ARB combined with an ACE inhibitor may benefit heart failure patients who are receiving all other recommended therapies. Further trials are needed to evaluate long-term safety effectiveness, quality of life, and survival before the combination can be recommended for routine use. PMID- 11215847 TI - The effect of helicobacter pylori eradication on NSAID-induced gastrointestinal toxicity. AB - OBJECTIVE: To review the data to determine whether Helicobacter pylori eradication alters nonsteroidal antiinflammatory drug (NSAID)-induced gastrointestinal toxicity. DATA SOURCE: Literature accessed through MEDLINE from 1966 to May2000 and abstracts of recently presented data at scientific meetings. DATA SYNTHESIS: NSAID use and H. pylon infection are independent risk factors for the development of gastrointestinal ulcers. An evaluation of the relationship between these two risk factors and the impact of H. pylori eradication on NSAID induced gastrointestinal toxicity was conducted. CONCLUSIONS: H. pylori colonization and NSAID use are independent risk factors for the development of gastrointestinal ulcers. The data regarding the interaction between these two risk factors in the development of gastrointestinal ulcers are conflicting. Eradication of H. pylori does not appear to decrease the risk of NSAID-induced gastrointestinal toxicity in the majority of patients. As there is little evidence to support a clear benefit of eradicating H. pylori in patients requiring NSAID therapy, routine screening for and eradication of H. pylori in these patients is not recommended. PMID- 11215848 TI - Postpartum alopecia. AB - OBJECTIVE: To determine whether there are effective treatments for postpartum alopecia. DATA SOURCES: Clinical literature identified through MEDLINE (January 1966-May 2000), EMBASE (June 1980-March 2000), and International Pharmaceutical Abstracts (January 1970-March 2000). Key search terms included alopecia, puerperium, and postpartum. DATA SYNTHESIS: Postpartum alopecia is a diffuse shedding of scalp hair that can begin two to five months following parturition. Few articles examine the treatment of this condition. Treatments in the form of thyroid supplementation, topical progesterone and estradiol lotions, and an oral contraceptive have been studied. All available studies on this subject have significant limitations, such as small sample size, absence of a control group, or subjective measurement of treatment response. Nondrug therapy for a related type of hair loss has been recommended and includes education about hair cycles and reassurance to minimize anxiety. CONCLUSIONS: From the available studies, no specific treatment has been studied well enough with sufficient treatment justify recommendation or to be termed effective. PMID- 11215849 TI - Dalteparin-induced retroperitoneal bleeding. PMID- 11215850 TI - Development of an intensive care unit bedside sedation scale. PMID- 11215851 TI - GERD and H. pylori: is there a link? AB - The incidence of gastroesophageal reflux disease (GERD) and esophageal adenocarcinoma have increased in recent years as the incidence of peptic ulcer disease and distal gastric cancer have declined. Given the simultaneous decline in Helicobacter pylori infection, it is tempting to propose a relationship between H. pylori infection and these opposing time trends. Although H. pylori infection clearly does not cause GERD, it may protect certain susceptible individuals from developing GERD and its complications. The most likely mechanism in which H. pylori infection protects against GERD is by decreasing the potency of the gastric refluxate in patients with corpus predominant gastritis. A variety of implications of H. pylori infection on GERD treatment have also arisen in recent years. These focus on the risk of gastric atrophy while on proton pump inhibitor therapy and the efficacy of proton pump inhibitors before and after eradication of H. pylori. This article puts into perspective our current understanding of the complex, incompletely understood relationship between H. pylori infection and GERD. PMID- 11215852 TI - Controversies in Barrett's esophagus: management of high grade dysplasia. AB - Barrett's esophagus is the premalignant lesion for adenocarcinoma of the esophagus and the esophagogastric junction. The incidence of esophageal adenocarcinoma has been rapidly rising in the Western world over the last two decades, and Barrett's esophagus is the only known premalignant lesion for this cancer. Esophageal adenocarcinoma develops through the metaplasia-dysplasia sequence with progression from no dysplasia, low grade dysplasia, high grade dysplasia, and ultimately to esophageal adenocarcinoma. The diagnosis and management of high grade dysplasia (HGD) in patients with Barrett's esophagus is extremely controversial. Patients with HGD within Barrett's esophagus are at the highest risk for development of esophageal adenocarcinoma if concurrent adenocarcinoma doesn't already exist. Given the high likelihood of metastatic disease and poor prognosis associated with invasive cancer, detection of HGD within Barrett's esophagus is considered by many as the final endpoint requiring definitive therapy in the form of surgical resection. However, other limited data seem to suggest that a number of patients with HGD may actually regress or persist and not develop cancer, thus suggesting a less aggressive approach for management. Finally with the advent of local endoscopic therapy, reversal therapy is being studied in patients with HGD and may be validated for this major indication. Currently, surgery remains the goal standard and the most definitive therapy for HGD. This articles critically reviews the risks and benefits associated with each approach of managing HGD. PMID- 11215853 TI - Management of GERD: medical versus surgical. AB - Both laparoscopic Nissen fundoplication and proton pump inhibitors are effective modern therapies for reflux disease that have yet to be directly compared in a well-designed clinical trial. In terms of a risk/benefit analysis, the risk of an undesirable outcome or death from laparoscopic Nissen fundoplication exceeds that of maintenance treatment with proton pump inhibitors making the later the preferable therapy. Neither therapy increases or reduces the risk of death from cancer and there are no compelling economic arguments favoring surgical management. Instances in which laparoscopic Nissen fundoplication should be considered include: 1) Individuals who are intolerant of proton pump inhibitor therapy because of side effects, 2) When patients are inadequately responsive to proton pump inhibitor therapy even after dosage and dose interval have been optimized, and 3) When a patient desires a permanent solution to their reflux problem that frees them of the need to chronically consume pharmaceuticals. However, regardless of the motivation for pursuing surgical management, patients must be advised of potential suboptimal results and the irreversibility of the procedure. PMID- 11215854 TI - Nonerosive reflux disease. AB - Until recently, the finding of erosive esophagitis in patients with chronic heartburn was thought to indicate more severe gastroesophageal reflux disease. However, recent data suggests that this is not necessarily true. Seventy-five percent of patient's chronic heartburn have moderate to severe symptoms, regardless of the presence or absence of esophagitis. Nonerosive reflux disease (NERD) is characterized by heartburn symptoms for at least 3 months with no evidence of esophagitis. Patients with NERD are similar to patients with esophagitis in symptom severity, quality of life scores, and response to anti reflux therapy. There are probably 3 distinct groups of NERD patients, those with pathologic reflux, those with a heightened sensitivity to physiologic reflux and those with other medical problems mistaken for reflux. This article discusses the 3 clinical scenarios. PMID- 11215855 TI - Gastroesophageal reflux disease: extraesophageal manifestations and therapy. AB - Gastroesophageal reflux disease (GERD) can present with both typical symptoms such as heartburn and regurgitation as well as atypical symptoms. These symptoms may include chest pain, asthma, chronic cough, hoarseness, otitis media, atypical loss of dental enamel, idiopathic pulmonary fibrosis, recurrent pneumonia, chronic bronchitis and even sudden infant death. The diagnosis of GERD in these patients can often present a challenge and usually requires a combination of selected testing and therapeutic trials. Acid suppression by using proton pump inhibitors remains the treatment of choice in GERD, but some patients will also respond well to antireflux surgery. This article addresses the presentations, diagnostic challenges, and therapeutic opportunities in GERD patients with atypical presentations. PMID- 11215856 TI - Diabetes mellitus in young Thai adults. AB - The purposes of the present study were to 1) find the prevalence of various types of diabetes; 2) determine the prevalence of glutamate decarboxylase autoantibody (anti-GAD) and 3) identify clinical characteristics which may help in predicting insulin deficiency in young Thai adults with diabetes. Subjects consisted of 93 adults with diabetes mellitus aged 15-40 years. In each subject, basal and post glucagon C-peptide levels were determined by radioimmunoassay. Anti-GAD was measured by radioimmunoassay and mitochondrial 3243 tRNA(Leu(UUR)) gene mutation was detected by PCR-RFLP. Data were expressed as mean +/- SEM. The mean age of subjects was 31.0 +/- 0.7 years with age at diagnosis of 25.6 +/- 0.9 years. Thirty nine (41.9%) were males and 54 (58.1%) were females. Pancreatic calcification was found in 7 (7.5%) of the patients while 2 (2.2%) were identified as having Wolfram syndrome. Four (4.3%) had nonketotic diabetes with affected family members in multiple generations consistent with MODY. Mitochondrial 3234 tRNA(Leu(UUR)) gene mutation was detected in only one patient. After excluding 14 subjects with pancreatic calcification, Wolfram's syndrome, MODY or mitochondrial gene mutation, 45 (57.0%) were found to be insulin deficient and 34 (43.0%) were insulin-sufficient based on post-glucagon C-peptide levels. Using stepwise logistic regression analysis, it was found that younger age at diagnosis (p<0.001), smaller waist circumference (p<0.01), previous history of DKA (p<0.01) was significantly associated with insulin deficiency. After excluding patients with DKA, younger age at diagnosis of diabetes (p<0.05) and lower BMI (p<0.01) were related to insulin deficiency. Concerning the role of autoimmunity, it was found that 13 (28.3%) of insulin-deficient subjects were positive for anti-GAD while 4 (11.8%) of those who were insulin-sufficient had positive results. Of the 54 patients currently on insulin, 42 (77.8%) are insulin deficient and 14 (25.9%) have positive anti-GAD. There were 10 (18.5%) who were both insulin sufficient and negative for anti-GAD suggesting that insulin therapy may not be required. We concluded that about half of young Thai adults with diabetes are not insulin-deficient and treatment with insulin may be unnecessary. The prevalence of glutamate decarboxylase antibody and mitochondrial 3234 tRNA(Leu(UUR)) gene mutation is low and as yet undefined factors are accountable for insulin deficiency in a significant number of patients. PMID- 11215857 TI - Food poisoning outbreak from contaminated fish-balls. AB - On February 9th, 1998, a food poisoning outbreak occurred at a boarding school for underprivileged students. An unmatched case-control study was done. An environmental survey, laboratory study of rectal swab culture, fish-balls, water and the cooking utensils were also performed. There were 132 suspect cases, of which the attack rate in teachers was 9.8 per cent (4/41), 16.7 per cent (1/6) in the food handlers and 15.7 per cent (127/810) in the students. The median incubation period was 18 hours. Analysis of food consumption revealed those who ate lunch noodles had the highest risk (OR 3.8, 95% CI 0.6-5.9). In details of food components, those who ate fish-balls in curry had the only significant risk (OR 3.5, 95% CI 1.2-0.8) of becoming ill when compared to those who did not. Fish balls in noodles and curry had a dose response relationship. Bacterial culture from 25 grams of fish-balls was positive for Vibrio parahaemolyticus. The fish balls in noodles and curry were identified as the implicated food. The modes of contamination were uncooked food, cooking utensils and the food handlers. The manufacturer, which had no license to operate and had poor standards of sanitation, was closed by the Food and Drug Administration. PMID- 11215859 TI - Efficacy of intranasal stent with filters for different laser smoke particle concentration. AB - Intranasal, hollow, cylindrical, medical grade, silicone stent with two layers and one layer of half face mask outer filter at each end was tested with different concentrations of laser smoke particles. A single pulse mode of carbon dioxide laser smoke particle created suitable polydisperse atmospheric suspended particulate matter amount. The personal respiratory protective device efficacy was done at the Otolaryngology Department, Ramathibodi Hospital from July to September 1998. The Whatman filter had the same laser smoke particle amount that passed through each filter of the intranasal stent. The cyclical air flow rate of 2 l/min in the nasal model was controlled by a lung model machine and respirometer. The particle deposition in filter materials was counted under a high power optical microscope. The filtration efficacy of an intranasal stent with filters for 5, 10 and 20 shots of laser smoke particle were 90.5, 94.6 and 95.6 per cent respectively with a mean of 93.6 per cent. The device application in a human nasal vestibule depended on acceptable nasal air flow resistant in various highly air-polluted areas. PMID- 11215858 TI - Significance of a widened mediastinum in blunt chest trauma patients. AB - Eighteen blunt chest trauma patients who had mediastinal widening on chest roengenogram were studied for the correlation with traumatic ruptured of the aorta or its major branches. Seventeen patients were male and one was female. The age ranged from 18 to 39 years, mean 26.17+/-6.85SD. The Injury Severity Score (ISS) ranged from 9 to 34, mean 25.5+/-6.49SD. Fourteen patients (77.8%) sustained motorcycle accidents, 3 patients (16.7%) sustained car accidents and 1 patient (5.5%) fell from a 4 storey building. All patients underwent aortography to search for traumatic rupture of the aorta or its major branches. Six patients had computed tomography of the chest before aortography. Nine patients (50%) had normal aortography. The remaining 9 patients who had positive aortography underwent urgent thoracotomies, 8 of them had traumatic rupture of the aorta or its major branches, the remaining 1 patient had normal operative finding. Of the 8 patients who had traumatic rupture of the aorta or its major branches, 1 patient died. The mortality was 12.5 per cent. The rate of traumatic rupture of the aorta or its major branches in patients who had blunt chest trauma and widening of the mediastinum on chest roengenogram in our study was 44.4 per cent. The sensitivity of aortography for diagnosis of traumatic rupture of the aorta or its major branches was 100 per cent and the specificity was 90 per cent. On the basis of this study, we conclude that blunt chest trauma patients with widened mediastinum on chest roengenogram have a significantly high rate of traumatic rupture of the aorta or its major branches. All blunt chest trauma patients who have widened mediastinum on chest reongenogram should undergo further investigations to exclude traumatic rupture of the aorta or its major branches. We recommend aortography as the investigation of choice due to its accuracy and usefulness in management plan. PMID- 11215860 TI - Pharmacokinetic studies of cyclosporin in Thai kidney transplantation patients. AB - Pharmacokinetic studies were performed in 10 Thai patients with kidney transplantation who received microemulsion formulation (Neoral) of cyclosporin A (CsA) twice daily. No agents having pharmacokinetic effect on CsA had been used in these patients. The mean values of 12-h AUC (area under the concentration blood curve) were 4603.63 +/- 344.61 ng x h/ml. CsA concentrations at 2 hours after dosing had the best value of correlation coefficient with the 12-h AUC. Abbreviated AUC could be calculated by stepwise multiple linear regression analysis and linear trapezoidal rule. The latter is more simple and superior to the former one. PMID- 11215861 TI - Development of coagglutination reagents for serological grouping of streptococci. AB - Coagglutination reagents for the rapid serological grouping of groups A, B, C, F and G Streptococcus have been developed. Antisera to groups A, B, C, F and G Streptococcus were raised in rabbits. After absorption with cross-reacting antigens, the specific antibodies were coated on Staphylococcus protein-A and used as group-specific coagglutination reagents. The sensitivity of the reagents for groups A, C and G Streptococcus was 100 per cent and the specificity was 100, 100, and 98.77 per cent, respectively. The sensitivity and specificity of these reagents were consistent up to 12 months, although specificity declined with longer storage. The in-house coagglutination reagents for groups A, C and G streptococcus were also tested in comparison with the commercially available Streptococcus Phadebact test and yielded almost identical results. Sensitivity of the in-house of group B Streptococcus reagent was low, while the group F reagent gave a high incidence of false positive reaction. PMID- 11215862 TI - A multicenter randomized double-blind comparison of remifentanil and alfentanil during total intravenous anaesthesia for out-patient laparoscopic gynaecological procedures. AB - We compared Remifentanil, an esterase-metabolized opioid, with Alfentanil as part of the total intravenous anesthesia with propofol and atracurium for out-patient laparoscopic gynaecological procedures in a multicenter randomized, double-blind study. We chose Remifentanil 1 mg./kg.for bolus injection and a continuous infusion of 0.25-0.5 microg./kg./min, compared to Alfentanil 20 microg./kg. For bolus injection and a continuous infusion of 0.5-1 microg./kg./min. Fifty-nine patients received Remifentanil, and sixty-three received Alfentanil. Patients who received Remifetanil experienced significantly fewer stress responses to surgical stimuli (p < 0.05) and required fewer additional boluses of study drugs and propofol (p < 0.05) than Alfentanil during the intraoperative period. Response time to verbal commands, spontaneous respiration, adequate respiration and tracheal extubation, were not significantly different between these two opioids. Remifentanil patients, required more fentanyl for post operative pain control, 40 from 59 cases in the Remifentanil group and 22 from 63 cases in the Alfentanil group (p < 0.05) but still showed significantly better recovery of psychomotor function by Aldrete score of ten at 50 and 60 min (p < 0.05) than Alfentanil patients. The incidence of intraoperative bradycardia was significantly higher with Remifentanil. Other incidences of nausea, emesis, urinary retention and postural hypotension were similar. All patients were ready to be discharged from the hospital within two hours after extubation except for one patient in the Alfentanil group who needed five hours of hospital stay because of urinary retention, nausea and severe emesis. PMID- 11215863 TI - Genotyping of human platelet antigens in ethnic Northeastern Thais by the polymerase chain reaction-sequence specific primer technique. AB - Human platelet antigens (HPA) are important in neonatal alloimmune thrombocytopenia (NAITP), post-transfusion purpura (PTP), refractoriness to platelet transfusion therapy and population genetics. The distribution of HPA in a Northeast Thai population was studied. 300 healthy, unrelated, and ethnic Northeastern Thais were randomly selected. Using the polymerase chain reaction sequence specific primer technique (PCR-SSP), the frequency of HPA-1, -2, -3, -4, -5 and -6 were determined. The phenotype frequencies were 100 per cent for HPA 1a, 4a, 5a, and 6a. For HPA-1b, 2a, 2b, 3a, 3b, 5b and 6b, the frequencies were 5.7, 99.7, 12.3, 78.0, 71.3, 7.3 and 3.0 per cent, respectively. The HPA-4b was not found. The HPA frequencies in our subjects were quite similar to other Asian populations but were different from Caucasians. The distribution of HPA genotypes encountered in our study indicate that HPA-1a, -4a, -4b, -5a and -6a will not be involved in NAITP, PTP and refractoriness to platelet transfusion therapy in Northeastern Thais. Moreover, HPA-1b, -2a, -2b, -3a, -3b, -5b and -6b may induce alloantibodies in these patients. PMID- 11215864 TI - Radiofrequency catheter ablation in pediatrics: experience at Siriraj Hospital. AB - Tachyarrhythmia is one of the life threatening cardiac electrophysiology problems in children. It also affects quality of life of the patients. Radiofrequency catheter ablation (RFCA) has made a significant impact in the treatment of tachyarrhythmia since 1989. The present report is the first and largest report in Thai children. There have been 24 RFCA procedures in 21 children since it was initially performed at Siriraj Hospital from January 1996 to December 1999. The electrophysiology studies and medical records were analyzed retrospectively. Median age and weight at the time of the procedure were 11 (1.1-13) years old and 38.8 (6.8-78.2) kg respectively. The presenting symptoms were palpitation 66.7 per cent, presyncope 16.7 per cent, congestive heart failure and cardiogenic shock 8.3 per cent, syncope 4.2 per cent, and chest pain 4.2 per cent. Median duration of symptom was 3.5 (0.1-8.0) years. The underlying cardiac arrhythmias were Wolff Parkinson White (WPW) syndrome 50 per cent, concealed accessory pathway 16.7 per cent, atrioventricular node re-entry tachycardia (AVNRT) 16.7 per cent, atrial ectopic tachycardia (AET) 12.5 per cent, and WPW with AVNRT 4.2 per cent. The median fluoroscopy time and procedure time were 25 (4-145) minutes and 125 (60-320) minutes respectively. The median tachycardia cycle length was 332.5 (220-460) seconds. The immediate success rate was 21/24 (87.5%) procedures. The procedural complication was 1/24 (4.2%). Two patients (8.3%) had recurrences of tachycardia and were successfully controlled with antiarrhythmic drugs. CONCLUSION: RFCA is a safe, effective, and curative procedure with high success rate for pediatric tachyarrhythmias. PMID- 11215865 TI - Blood lactate determined by a portable device in critically ill patients. AB - Patients with tissue perfusion deficit usually have lactic acidosis or hyperlactacidemia and blood lactate level has been used to diagnose this condition and to monitor the disease progression. We conducted a study to examine the diagnostic accuracy of capillary and arterial lactate (C LAC and strip A LAC) obtained by using a portable lactate analyzer (Accusport) compared with the standard method (A LAC) in this condition. Forty eight patients were included in the study. Strong correlation between C LAC and A LAC as well as strip A LAC and A LAC were demonstrated (r = 0.89 and 0.98 respectively, p <0.05). When determining agreement between C LAC and strip A LAC with the standard method, all but 2 of C LAC - A LAC differences and 2 of strip A LAC - A LAC differences were within the agreement limits (mean +/- 2SD). We conclude that capillary and arterial lactate determined by the tested device, when used and interpreted cautiously, can substitute arterial lactate in the diagnosis of hyperlactacidemia and monitoring the effectiveness of therapy. PMID- 11215866 TI - Hyperhomocysteinemia in patients with coronary artery disease. AB - Hyperhomocysteinemia has been recognized as a risk factor of atherosclerosis. This study was aimed to measure the risk of coronary artery disease in patients with hyperhomocysteinemia. Age, HDL level, tHcy level and history of DM were independent risk factors for coronary artery disease. The level of tHcy of 11.0 mmol/L provides the best sensitivity and specificity of predicting coronary artery disease. PMID- 11215867 TI - Songkla uterine manipulator. AB - The Songkla Uterine Manipulator (SUM) was developed for laparoscopic procedures. Its shaft consists of two stainless steel rods, which pivot a head and locking system. The obturator has a plate and is connected to the pivot head with a screw. The obturator has a diameter of 4.7 mm with three standard lengths of 6, 8, and 10 cm and there is a spring hook to retain it with the tenaculum. The SUM allows antevertion of the uterus up to 95 degrees and lateral motion of about 45 degrees bilaterally. From December 1996 to December 1999, the SUM was used successfully in 150 laparoscopic procedures, including 51 tubal sterilizations, 42 cases of adnexal surgery, 12 total laparoscopic hysterectomies and 45 laparoscopic assisted vaginal hysterectomies. The visualization of pelvic organs including both adnexae was good in all cases without trauma to the vagina, cervix or uterus. CONCLUSION: The simplified low cost uterine manipulator was developed. Early results were good but more modifications are needed, such as mechanism to retain it to the cervix without the tenaculum and sealing of gas leakage from the vagina during laparoscopic hysterectomy. PMID- 11215868 TI - Tricyclic antidepressants for depressive disorders in children and adolescents: a meta-analysis of randomized-controlled trials. AB - The tricyclic antidepressants (TCAs) are effective for the treatment of adult depression. However, their efficacy of these in the treatment of children and adolescents with depression is equivocal. Therefore, it is necessary to determine the efficacy and acceptability of TCAs in the treatment of depressive disorders in children and adolescents. The databases of MEDLINE (from 1966 to October 1999) and Controlled Clinical Trials Registered (from 1980 to October 1999) were searched for randomized-controlled trials relevant to the use of TCAs for treating depressed children and adolescents. The reviewers also examined the reference lists of identified papers and that of a previous meta-analysis. In each trial, both nonresponse rates and dropout rates were taken into account and extracted on an intention-to-treat basis. The nonresponse-rate and dropout-rate odd ratios (ORs) with 95 per cent confidence intervals (95% CIs) of each trial and the pooled non-response-rate and dropout-rate ORs (95% CIs) of all trials were computed. Nine trials included in this meta-analysis were 2 amitriptyline, 3 desipramine, 2 imipramine, and 2 nortriptyline studies. By using a fixed-effect model, the pooled nonresponse-rate OR (95% CI) and the pooled dropout rate OR (95% CI) of antidepressant-treated group were 0.92 (0.57 to 1.47) and 2.14 (1.12 to 4.09), respectively. In summary, the evidence so far does not support that TCAs are more effective or more acceptable than placebo in the treatment of depressive disorders in children and adolescents. However, the studies of selective serotonin reuptake inhibitors and newer antidepressants for the treatment of these disorders should be further investigated. PMID- 11215869 TI - Nutritional problems in children aged 1-24 months: comparison of hill-tribe and Thai children. AB - A cross-sectional survey was conducted in Maecham district, Chiang Mai. The objective was to determine the magnitude of nutritional problems in children aged 1-24 months, both of hill-tribe and Thai communities, where breast-feeding is highly prevalent. Three hundred and fifty nine children were recruited, 252 were hill-tribe (Karen and Lahu), and 107 were Thai children. Anthropometric measurements were taken and mothers were interviewed. In a group of hill-tribe children, the prevalence of malnutrition (Z score of weight for age < -2) was 25.0 compared with 12.1 per cent for Thai children (p <0.01). The prevalence was highest in children aged between 12-24 months. This corresponded to the time children were weaned. The prevalence of stunting (Z score of height for age < -2) in hill-tribe and Thai children was 25.4 and 12.1 per cent respectively (p <0.01). There was no significant difference of wasting (Z score of weight for height < -2) between hill-tribe and Thai children, 9.1 and 8.4 per cent respectively. The mean (SD) Z scores of weight for age, weight for height, and height for age for both groups declined significantly as the age increased (p <0.001). In conclusion, this study revealed the nutritional problems of young hill-tribe children were more severe than those of Thai children. The factors that could be related with this, were socioeconomic status, as also genetics, as well as cultural beliefs concerning child raising. Such ethnic minorities therefore should be considered as special cases in programs of health and nutrition promotion. PMID- 11215870 TI - A Thai boy with hereditary enzymopenic methemoglobinemia type II. AB - Individuals with methemoglobin exceeding 1.5 g/dl have clinically obvious central cyanosis. Hereditary methemoglobinemia is due either to autosomal dominant M hemoglobins or to autosomal recessive enzymopenic methemoglobinemia. Four types of enzymopenic methemoglobinemia have been described. In addition to methemoglobinemia, individuals with type II, which is the generalized cytochrome b5 reductase deficiency, have severe and progressive neurological disabilities. Here we report a 3-year-old Thai boy with type II hereditary enzymopenic methemoglobinemia. He was born to a second-cousin couple. His central cyanosis was first observed around 10 months of age. His neurological abnormalities were seizures beginning at 1 year of age, microcephaly, and inability to hold his head up. His cardiovascular and pulmonary evaluations were unremarkable. Methemoglobin level by spectral absorption pattern was 18 per cent. A qualitative enzymatic assay confirmed the deficiency of the cytochrome b5 reductase enzyme. With this definite diagnosis, a prenatal diagnosis for the next child of this couple will be possible. PMID- 11215871 TI - Poor physical fitness of adolescents with mental retardation at Rajanukul School, Bangkok. AB - OBJECTIVE: To study the physical condition of adolescents with mild to moderate mental retardation (MR), twenty-eight MR students from Rajanukul school were evaluated for their fitness components compared to 14 normal students. METHOD: Per cent body fat (%BF) was calculated from three sites of skinfold thickness. The cardiorespiratory endurance was assessed using graded exercise testing and Quinton gas analyzer. Isometric leg strength was measured with dynamometer, and flexibility was measured by sit and reach test. RESULTS: Compared between MR and normal subjects, %BF was higher in the MR group without statistic significance. Five MR females had %BF > 30. The mean VO2peak was about 70 per cent of normal. The leg strength and flexibility were very poor. CONCLUSION: The MR adolescents had a significantly lower level of physical fitness and more prevalence of obesity than normal students. Appropriate physical activities should be emphasized for health promotion and disease prevention. PMID- 11215872 TI - Transcatheter oily chemoembolization of the extrahepatic collaterals in hepatocellular carcinoma. AB - Twenty patients with hepatocellular carcinoma who had hepatic artery occlusion from repeated transcatheter oily chemoembolization (TOCE), were treated with additional TOCE through extrahepatic collaterals. Repeated TOCE were performed through the inferior phrenic artery (10 patients), branches of the gastroduodenal artery (6 patients), the internal mammary artery (2 patients), the pancreatico duodenal arcade (1 patient), the accessory hepatic artery (1 patient), the capsular branch of the right renal artery (1 patient) and the 12th intercostal artery (1 patient). The TOCE was unsuccessful in 4 patients with accessory hepatic artery, one patient with cystic artery arising from superior mesenteric artery, one patient with omentoepiploic artery and one patient with left gastric anastomose with right gastric artery. The success rate of TOCE in the extrahepatic arteries was 76.67 per cent while there was a 23.33 per cent failure rate. The overall cumulative survival rates were 80 per cent (6 months), 50 per cent (12 months) and 18.8 per cent (18 months). One patient developed skin necrosis at the right chest wall following TOCE of the right internal mammary artery for HCC. One patient developed hemiplegia following TOCE of the right 12th intercostal artery. The extrahepatic collaterals are important alternative routes for continuous transcatheter management of hepatocellular carcinoma following hepatic artery occlusion. PMID- 11215874 TI - Acute external laryngeal injury. AB - A retrospective study of 35 patients with acute external laryngeal injury who were treated at Maharaj Nakorn Chiang Mai Hospital from January 1989 to 1998 was done. Eighty-six per cent of the patients with blunt trauma had been injured from a motor vehicle accident and the rest had a penetrating injury from a stab wound. The frequent signs and symptoms were hoarseness, skin contusion, pain and subcutaneous emphysema. The severity of the injury was classified into minor and major groups. There were 2 patients in the minor group and 33 in the major group. Both patients in the minor injury group had good result from conservative treatment. All patients in the major injury group, except one with left vocal cord paralysis, required surgical management. No airway problem was found in any patient and only one patient had unintelligible voice after treatment. Twenty three per cent had minor complications and responded well to conventional treatment. Early diagnosis and proper management gave the best outcome of the patient's airway and voice. PMID- 11215873 TI - Immunohistochemistry for intestinal ganglion cells and nerve fibers: aid in the diagnosis of Hirschsprung's disease. AB - Hirschsprung's disease is a disease of congenital abnormalities characterized by absence of the enteric ganglion cell of the colon. To make a definite diagnosis, biopsy of the aganglionic zones of colon is required. A specimen from submucosal biopsy of the colon is very small and difficult to identify submucosal ganglion cells. Our study reports an immunohistochemical technique to detect submucosal ganglion cells. Six antineural markers, peripherin, cathepsin D, PGP 9.5, synaptophysin, chromogranin and S-100 protein, were used. The best antibody for the detection of submucosal ganglion cells in our study was peripherin. The additional measurement of nerve fiber caliber using S-100 protein staining is a valuable aid in the diagnosis of Hirschsprung's disease. It can be applied to the suction submucosal biopsy in a patient suspected of having Hirschsprung's disease, therefore, the complicated full thickness colonic and rectal biopsy can be avoided. PMID- 11215875 TI - Preschool sarcoidosis. AB - Sarcoidosis is a multisystemic granulomatous disorder of unknown etiology, most commonly affecting young adults and presenting most frequently with bilateral hilar lymphadenopathy, pulmonary infiltration, and skin or eye lesions. Sarcoidosis in children under the age of 4, preschool sarcoidosis, is rare and has very different clinical mainfestations characterized by the typical triad of skin, eye and joint involvement without lung disease. Diagnosis is established when compatible clinical findings are supported by histological evidence of widespread noncaseating epithelioid-cell granulomas in more than one organ or a positive Kveim-Siltzbach skin test. This report describes a 2-year-old Thai girl with typical clinical manifestations of preschool sarcoidosis. The histopathological studies of tissue specimens and the laboratory investigations support the diagnosis of sarcoidosis. The patient responded to systemic corticosteroid therapy. PMID- 11215876 TI - Pseudotumor cerebri caused by all-trans-retinoic acid: a case report. AB - Pseudotumor cerebri is a condition characterized by increased intracranial pressure with normal cerebrospinal fluid composition. It is usually associated with many medical conditions and drugs. It has been reported that all-trans retinoic acid can induce pseudotumor cerebri. The authors report a 35-year-old patient diagnosed with acute promyelocytic leukemia who developed pseudotumor cerebri after receiving all-trans-retinoic acid. The patient was treated with 60 mg/day of all-trans-retinoic acid. Two weeks later, she had severe headache and blurred vision. The neurological examination revealed papilledema and decreased visual acuity. Other physical examinations were unremarkable. Brain CT was normal. Additionally, lumbar puncture was performed and the CSF finding was normal except for high CSF pressure. According to modified Dandy criteria, the diagnosis was pseudotumor cerebri. The patient's symptoms disappeared after all trans-retinoic acid was discontinued. To our knowledge, this is the first case report in Thailand. PMID- 11215877 TI - Extensive ossification in a craniopharyngioma. AB - A rare extensive ossification occurred in a suprasellar craniopharyngioma of a man who died at 21 years of age. The tumor produced headache, retarded physical and mental development, visual disturbances, and increased intracranial pressure. The neoplasm recurred after surgical and roentgenological treatments. Differentiation of multipotential mesenchymal cells or mesenchymal type cells within the tumor has been suggested as the mode of occurrence of bone in this craniopharyngioma. PMID- 11215878 TI - Improvement of tardive dyskinesia with risperidone: a case report. AB - This case report illustrates the improvement of tardive dyskinesia (TD) and psychotic symptoms in an elderly Thai female with chronic schizophrenia with a long history of conventional antipsychotic exposure following the treatment with risperidone 2 mg/day. TD disappeared in 9 months and continued to be in remission at her 5-month follow-up visit recently. PMID- 11215879 TI - The speech delivered by Professor Dr. Kasem Suwanagul at the press conference called by Deputy Prime Minister Pichai Ratakul to introduce the National Distinguished Citizen of 1998. PMID- 11215880 TI - Serosurveys for West Nile virus infection--New York and Connecticut counties, 2000. AB - In 2000, 21 persons were reported with acute illness attributed to West Nile virus (WNV) infection; 19 were hospitalized with encephalitis or meningitis. Of the 21, 10 resided in the Staten Island borough (Richmond County) of New York City. Other ill persons resided in nine other counties--Kings (Brooklyn), New York (Manhattan), and Queens counties in New York; Hudson, Passaic, Monmouth, Morris, and Bergen counties in New Jersey; and Fairfield County in Connecticut. Because ill persons represent only a fraction of the persons who are infected, many more persons probably were infected in 2000. To determine the prevalence of recently acquired WNV infection and associated risk factors for infection, random household cluster serosurveys were conducted in Staten Island and portions of Fairfield County, Connecticut, and Suffolk County, New York, during October November 2000. All three areas had intense WNV epizootics as determined by avian mortality and mosquito surveillance systems. This report summarizes the preliminary results of this survey and indicates that in areas with intense epizootic WNV activity, asymptomatic or mildly symptomatic human infections can occur. PMID- 11215881 TI - Influenza activity--United States, 2000-01 season. AB - This report summarizes influenza activity in the United States during November 26, 2000-January 13, 2001. Influenza activity was low to moderate but increasing in the United States. Since October 1, the most frequently isolated viruses were influenza A (H1N1) and were well matched antigenically with the 2000-01 influenza A (H1N1) vaccine strain. PMID- 11215882 TI - Circulation of a type 2 vaccine-derived poliovirus--Egypt, 1982-1993. AB - In 1988, the World Health Assembly resolved to eradicate poliomyelitis globally by 2000. Substantial progress has been achieved toward this goal, and with the circulation of wild poliovirus eliminated in most of the world, attention has focused on examining the potential for vaccine-derived poliovirus to circulate where wild poliovirus has disappeared. During 1999, sequences of historic poliovirus isolates were examined. This report summaries the results of that study, which indicate that oral poliovirus vaccine (OPV)-derived poliovirus type 2 circulated in Egypt during the 1980s and early 1990s and caused widespread infection and paralytic disease. The findings underscore the need for countries using OPV to target communities with low vaccine coverage for intense vaccination activities to prevent circulation of both wild and vaccine-derived polioviruses. PMID- 11215883 TI - Polysaccharide-based chiral stationary phases for high-performance liquid chromatographic enantioseparation. AB - Recent developments of polysaccharide-based chiral stationary phases (CSPs) for the direct separation of enantiomers in high-performance liquid chromatography (HPLC) are mainly reviewed together with the results on mechanistic studies by means of chromatography, NMR and mass spectroscopies, and computational methods. Miscellaneous applications of polysaccharide derivatives to the newly developed, chiral dynamic high-performance liquid chromatography (DHPLC) for obtaining a nonracemic compound are also described. PMID- 11215884 TI - Reversed-phase liquid chromatographic separation of enantiomers on polysaccharide type chiral stationary phases. AB - The direct chiral separation by chiral stationary phases (CSPs) is one of the most important techniques to analyze enantiomeric purity as well as to get enantiomerically pure material quickly. Among various types of CSPs, polysaccharide type CSPs are well known by their versatility and durability. They are not only effective under normal-phase conditions, but also under reversed phase conditions. In order to get a good separation under the reversed-phase conditions, it is the key to choose an appropriate mobile phase. For example, a simple mixture of water/acetonitrile or water/methanol are sufficient for a neutral analyte, while it is necessary to use an acidic solution instead of water for an acidic analyte and a solution of a chaotropic salt (or a basic solution) for a basic analyte, respectively. The paper also presents lists of more than 350 separation examples that include 22 validated methods for drug analyses from serum, plasma, or urine samples on polysaccharide type CSPs under reversed-phase conditions. PMID- 11215885 TI - Covalently bonded polysaccharide derivatives as chiral stationary phases in high performance liquid chromatography. AB - Polysaccharide derivatives have been extensively used as chromatographic chiral selectors in chiral stationary phases (CSPs) for the separation of enantiomers by HPLC. When coated onto a silica matrix, they represent nowadays one of the most popular type of CSPs. However, they are only compatible with a limited choice of solvents. The main drawback of these CSPs is related to the solubility of the chiral selector in a number of solvents, which limits their applicability. The different attempts which have been described up to now to overcome this problem by covalently fixing the chiral selector to a matrix are reviewed in this paper. PMID- 11215886 TI - Regioselectively modified polysaccharide derivatives as chiral stationary phases in high-performance liquid chromatography. AB - This review summarizes several regioselectively modified polysaccharide derivatives which have been prepared in order to be used for chiral separations chromatography. The goal was to combine the effects of the known tris arylcarbamate and tris-arylesters of polysaccharides. The use of new materials as chiral stationary phases (CSPs) in liquid chromatography for enantiomeric discrimination was investigated and compared to the homogeneously substituted polysaccharide derivatives. The different works describing the preparations, the performances and the applications of regioselectively modified polysaccharide derivatives have been resumed. PMID- 11215887 TI - High-performance liquid chromatographic enantioseparation of drugs containing multiple chiral centers on polysaccharide-type chiral stationary phases. AB - Enantioseparation of drugs with multiple chiral centers is challenging. This article describes resolution of some drugs with multiple chiral centers using polysaccharide-type chiral stationary phases. Also, the use of the column switching technique is demonstrated to achieve the resolution of this type of compounds. PMID- 11215888 TI - Unusual effects of separation conditions on chiral separations. AB - Unusual effects in liquid chromatographic separations of enantiomers on chiral stationary phases are reviewed with emphasis on polysaccharide phases. On protein phases and Pirkle phases reversal of the elution order between enantiomers due to variation of temperature and mobile phase composition has been reported. Most of the nonanticipated observations have dealt with the widely used polysaccharide phases. Reversed retention order and other stereoselective effects have been observed by variation of temperature, organic modifier and water content in nonpolar organic mobile phases. PMID- 11215889 TI - Optically active synthetic polymers as chiral stationary phases in HPLC. AB - Synthetic, optically active polymers used as CSP are reviewed. The polymers are classified into three major categories, namely, addition polymers, condensation polymers, and cross-linked gels. The emphasis lies on polymethacrylates having helical conformation belonging to the first category. Helical polymethacrylates are synthesized using asymmetric anionic or radical polymerization techniques and show resolving ability towards a wide range of racemate. PMID- 11215890 TI - Imprinted chiral stationary phases in high-performance liquid chromatography. AB - Polymers imprinted with chiral templates offer a new generation of tailor-made chiral stationary phases (CSPs) with predictable selectivities. This review summarizes the present state of the art of molecular imprinting to generate tailor-made CSPs and provides an overview of the main factors involved in the manufacturing process that are crucial to the chromatographic performance of the phases. PMID- 11215891 TI - Protein-based chiral stationary phases for high-performance liquid chromatography enantioseparations. AB - The enantioseparations of various compounds using proteins as the chiral selectors in high-performance liquid chromatography (HPLC) are considered in this review. The proteins used include albumins such as bovine serum albumin and human serum albumin, glycoproteins such as alpha1-acid glycoprotein, ovomucoid, ovoglycoprotein, avidin and riboflavin binding protein, enzymes such as trypsin, alpha-chymotrypsin, cellobiohydrolase I, lysozyme, pepsin and amyloglucosidase, and other proteins such as ovotransferrin and beta-lactoglobulin. This review deals with the properties of HPLC chiral stationary phases based on proteins, and the enantioselective properties and chiral recognition mechanisms of these stationary phases. PMID- 11215892 TI - Separation of enantiomers by gas chromatography. AB - The separation of enantiomers by gas chromatography is performed on chiral stationary phases (CSPs) via hydrogen bonding, coordination and inclusion. Thus, typical chiral selectors are amino acid derivatives, terpene-derived metal coordination compounds and modified cyclodextrins. In Chirasil-type stationary phases the chiral selector is anchored to a polysiloxane backbone improving gas chromatographic performance. The present review article describes the state-of the-art, scope and limitations, applications and mechanistic considerations at the advent of the millennium incorporating 16 figures and 168 references. PMID- 11215893 TI - Separation of enantiomers: needs, challenges, perspectives. AB - Chiral drugs, agrochemicals, food additives and fragrances represent classes of compounds with high economic and scientific potential. First the present implications of their chiral nature and necessity of separating enantiomers are summarised in this article. In the following a brief overview of the actual approaches to perform enantioseparations at analytical and preparative scale is given. Challenging aspects of these strategies, such as problems associated with data management, choice of suitable chiral selectors for given enantioseparations and enhanced understanding of the underlying chiral recognition principles, are discussed. Alternatives capable of meeting the requirements of industrial processes, in terms of productivity, cost-effectiveness and environmental issues (e.g., enantioselective membranes) are critically reviewed. The impact of combinatorial methodologies on faster and more effective development and optimisation of novel chiral selectors is outlined. Finally, the merits and limitations of most recent trends in discrimination of enantiomers, including advances in the fields of sensors, microanalysis systems, chiroptical methods and chemical force microscopy are evaluated. PMID- 11215894 TI - Enantioseparations in super- and subcritical fluid chromatography. AB - The separation of chiral compounds by sub- and supercritical fluid chromatography has been a field of great progress since the first demonstration of a chiral separation by SFC in 1985. Almost all of the chiral selectors used in gas or liquid chromatography have been successfully applied to sub-/supercritical chromatography. Easier and faster method development, high efficiency, superior and rapid separations of a wide variety of analytes, extended-temperature capability, analytical and preparative-scale equipment improvements and a selection of detection options have been reported. PMID- 11215895 TI - Enantioseparations in capillary electromigration techniques: recent developments and future trends. AB - This review summarizes the current status of enantioseparations using capillary electromigration techniques and gives the authors insights on the selected fundamental aspects and future trends in this field. The most recent developments in the field of chiral separations using capillary electrophoresis (CE) and capillary electrochromatography (CEC) are summarized. The status of chiral electromigration techniques is evaluated tacking into account the most recent developments in related techniques such as chiral HPLC, GC and SFC. PMID- 11215897 TI - Enantioseparations in counter-current chromatography and centrifugal partition chromatography. AB - Examples of chiral separations in counter-current chromatography (CCC) and centrifugal partition chromatography (CPC) are not numerous, due to the difficulty of finding chiral selectors highly selective in the liquid phase as well as a combination of solvents that does not destroy the selectivity and retains the capacity to elute chiral isomers of interest. New ideas and new chiral selectors generally come from other separation techniques, as will be highlighted in this review. PMID- 11215896 TI - High-performance liquid chromatography chiral stationary phases based on low molecular-mass selectors. AB - A review of HPLC chiral stationary phases (CSPs) based on low molecular mass selectors is given. The review is focused on brush- and monomeric-type CSPs obtained by covalent linkage of chiral selectors, with emphasis on those obtained by total synthesis. Emphasis is given to new, emerging aspects like enantioseparations on receptor-like chiral stationary phases and dynamic enantioselective chromatography of stereolabile compounds. PMID- 11215898 TI - Enantioselective chromatography as a powerful alternative for the preparation of drug enantiomers. AB - The preparative separation of enantiomers by chromatography on chiral stationary phases (CSPs) has been recognized as being a useful alternative to the more conventional approaches such as enantioselective synthesis and enzymatically catalyzed transformations. The possible contribution of enantioselective chromatography with respect to the preparation of enantiomerically pure compounds is reviewed in the context of the competitive approaches and depending on the application scale, with a special emphasis on the recent progresses achieved in this particular field of separation. PMID- 11215899 TI - Preparative enantioseparation by simulated moving bed chromatography. AB - Simulated moving bed (SMB) chromatography was invented in the 1960s in the petrochemical industry and has since then been widely used to produce petrochemicals and sugars at the multi-ton scale. In the early 1990s its principle could be successfully adapted to chromatographic enantioseparation, due to developments in system design, chiral stationary phase synthesis and improvements in modelling and simulation of non-linear chromatographic behaviour. Since then a lot of separation systems have been brought into production, which are reviewed. In addition new developments are outlined in the field of system design and stationary phase development. PMID- 11215900 TI - Atomistic modeling of enantioselection in chromatography. AB - A review of atomistic molecular modeling studies related to chromatographic separations of enantiomers is presented. Only those types of calculations where direct interactions between a selector and a selectand are involved are described in this review; omitted are regression models. An emphasis is placed on comparing methods used for sampling potential energy surfaces implementing different methodologies like quantum and molecular mechanics for energy calculations, and molecular dynamics and Monte Carlo sampling strategies for simulations. Type I-V chiral stationary phases and additives for capillary electrophoresis and ion-pair chromatography are covered in this review. PMID- 11215902 TI - Chromatographic and electrophoretic studies of protein binding to chiral solutes. AB - Protein interactions are important in determining the transport, metabolism and/or activity of many chiral compounds within the body. This review examines data that have been obtained on these interactions by various chromatographic and electrophoretic methods, especially those based on either high-performance liquid chromatography or capillary electrophoresis. Zonal elution, frontal analysis and vacancy methods are each considered, as are approaches that employ either soluble or immobilized proteins. There are a variety of different items that can be learned about a solute-protein system through these techniques. This includes information on the binding constants and number of binding sites for a solute protein system, as well as the thermodynamic parameters, rate constants, interaction forces and binding site structure for the protein and solute. Numerous examples are provided throughout this review, as taken from the literature and from work performed within the author's laboratory. PMID- 11215901 TI - Reviewing mobile phases used on Chiralcel OD through an application of data mining tools to CHIRBASE database. AB - During the past decade, thousands of compounds have been resolved on Chiralcel OD (a cellulose-based chiral stationary phase) under diverse eluting conditions. Many researches have documented the effects of mobile phase on enantioselectivity for a given family of samples but today no comprehensive study aimed at identifying the associations between the structural features present on solute and appropriate mobile phase conditions has yet been proposed. In this review of mobile phases used on Chiralcel OD, we try to go far beyond a simple enumeration of eluting conditions and an effort is made to explore the utility of data mining tools for assessing the knowledge contained in CHIRBASE database. We have extracted from CHIRBASE the chemical features of 2363 chiral compounds separated on Chiralcel OD and their corresponding mobile phases. This data set was submitted to data mining programs for molecular pattern recognition and mobile phase predictions for new cases. Some substructural characteristics of solutes were related to the efficient use of some specific mobile phases. For example, the application of CH3CN/salt buffer at pH 6-7 was found convenient for reversed phase separation of compounds bearing a tertiary amine functional group. Furthermore, a cluster analysis allowed the arrangement of the mobile phases according to similarity found in molecular patterns of solutes. A decision tree, which may lead to a more rational choice of the mobile phase under reversed-phase conditions, is also proposed. PMID- 11215903 TI - Chiral chromatographic separations based on ligand exchange. AB - Taking ligand-exchange chromatographic systems as an example, the effect of the stoichiometry of the solute-chiral selector interaction on the efficiency, selectivity and solute peak profile is discussed. Recent achievements and practical applications of chiral ligand-exchange chromatography are also briefly reviewed. PMID- 11215904 TI - Chiral separations using the macrocyclic antibiotics: a review. AB - The macrocyclic antibiotics have recently gained popularity as chiral selectors in CE, HPLC and TLC. The macrocyclic antibiotics used for chiral separations include the ansamycins, the glycopeptides, and the polypeptide antibiotic thiostrepton. Although not strictly considered macrocyclic antibiotics, the aminoglycosides are antibiotics that have been used for chiral separations in CE. More chiral analytes have been resolved using the glycopeptides than with the other macrocyclic antibiotics combined. The glycopeptides vancomycin, ristocetin A and teicoplanin have been used extensively as chiral selectors in CE, with ristocetin A appearing to be the most useful chiral selector followed by vancomycin and teicoplanin, respectively. The macrocyclic antibiotics have also been used as chiral bonded phases in HPLC, and HPLC stationary phases based on vancomycin, ristocetin A and teicoplanin have been commercialized. Ristocetin A seems to be the most useful glycopeptide HPLC bonded phase, but its greater expense can be a drawback. The macrocyclic antibiotics have been used with micelles to improve efficiency, provide unique selectivity, and extend the range of separations to neutral solutes. Changing the macrocyclic antibiotic used in CE or HPLC can significantly alter the enantioselectivity of the separations. In fact, the glycopeptide antibiotics are complementary to one another, where if a partial enantioresolution is obtained with one glycopeptide, there is a high probability that a baseline or better separation can be obtained with another. PMID- 11215905 TI - High-performance liquid chromatographic and capillary electrophoretic enantioseparation of plant growth regulators and related indole compounds using macrocyclic antibiotics as chiral selectors. AB - Enantioseparation of plant growth regulators, such as 3-(3-indolyl)-butyric acid, abscisic acid and structurally related molecules including a variety of substituted tryptophan compounds, has been achieved by HPLC and/or CE. The covalently bonded macrocyclic antibiotics, teicoplanin, ristocetin A and vancomycin, were used as chiral stationary phases (CSPs) in HPLC. Most of the racemates were baseline resolved in the reversed-phase mode (EtOH-H2O) using the teicoplanin CSP. The chiral recognition mechanism is discussed in regard to the structure of the analytes. In CE, the three aforementioned macrocyclic antibiotics were used as chiral additives in a phosphate run buffer. The effect of pH and the concentration of the organic modifiers were considered. The results obtained by HPLC and CE were compared. PMID- 11215906 TI - Immune cell populations within the duodenal mucosa of dogs with enteropathies. AB - The mucosal immune system may play a critical role in the pathogenesis of small intestinal enteropathies. The aim of the current study was to assess mucosal immune cell populations in dogs with inflammatory bowel disease (IBD), idiopathic antibiotic-responsive diarrhea (ARD), and adverse reactions to food (FR). Endoscopic biopsies were performed of the duodenum of dogs with these conditions and from a group of dogs without enteric disease. Additional control samples were collected after death from other dogs that did not have evidence of enteric disease. Immunohistochemistry and computer-aided morphometry were used to assess the distribution of immune cell subsets in both lamina propria and intestinal epithelium. Compared with controls, dogs with ARD had increased numbers of lamina propria immunoglobulin (Ig) A- plasma cells and CD4+ cells. More marked alterations were noted in dogs with IBD, with significant increases in lamina propria IgG+ plasma cells, T cells (CD3+), CD4+ cells, macrophages, and neutrophils, but with reduced mast cell numbers. Increased intraepithelial CD3+ T cells were also present in the dogs with IBD, compared with controls. However, lamina propria and epithelial populations were unaltered in dogs with FR when compared with controls. The altered mucosal immune cell populations observed in dogs with ARD or IBD may reflect an underlying immunologic pathogenesis in these disorders. PMID- 11215907 TI - Subnormal concentrations of serum cobalamin (vitamin B12) in cats with gastrointestinal disease. AB - The present study sought to determine the spectrum of diseases associated with subnormal concentrations of serum cobalamin in cats undergoing investigation of suspected gastrointestinal problems. The solid-phase boil radioassay (RA) for cobalamin employed in the present study was immunologically specific, precise, and accurate, with a sensitivity of 15 pg/mL. The RA yielded results that strongly correlated with those obtained by bioassay (Spearmann rho = .805; P < .0001), although the absolute values were lower for the RA. Forty-nine of 80 serum samples submitted during the period of January 1996-January 1998 had cobalamin concentrations below the reference range for healthy cats (range 900 2,800 pg/mL; mean +/- SD, 1,775 +/- 535 pg/mL; n = 33). Cats with subnormal cobalamin concentrations (mean +/- SD; 384 +/- 272 pg/mL, range 3-883 pg/mL) were middle-aged or older and were presented for weight loss. diarrhea, vomiting, anorexia, and thickened intestines. Definitive diagnoses in 22 cats included inflammatory bowel disease (IBD), intestinal lymphoma, cholangiohepatitis or cholangits, and pancreatic inflammation. Serum concentrations of cobalamin were particularly low in cats with intestinal lymphoma, three-fifths of whom also had subnormal serum concentrations of folate (< 9 ng/mL). The simultaneous presence of disease in the intestines, pancreas, or hepatobiliary system in many cats made it difficult to determine the cause of subnormal cobalamin concentrations. The circulating half-life of parenteral cyanocobalamin was shorter in 2 cats with IBD (5 days) than in 4 healthy cats (12.75 days). The presence of subnormal serum concentrations of cobalamin in 49 of 80 cats evaluated suggests that the measurement of serum cobalamin may be a useful indirect indicator of enteric or pancreatic disease in cats. The rapid depletion of circulating cobalamin in cats suggests that cats may be highly susceptible to cobalamin deficiency. However, the relationship of subnormal serum cobalamin concentrations to cobalamin deficiency and the effect of cobalamin deficiency on cats remain to be determined. PMID- 11215908 TI - Prevalence of enteric zoonotic agents in cats less than 1 year old in central New York State. AB - A prevalence study of several enteric zoonotic bacterial and parasitic infections was conducted in 263 fecal samples from cats that were between 1 and 12 months old, and that were in humane shelters (n = 149) or were presented to primary-care veterinarians (n = 114). Of these samples, 2 (0.8%) were positive for Campylobacter, 2 (0.8%) were positive for Salmonella, and 10 (3.8%) were positive for Cryptosporidium, confirming that these zoonotic agents are relatively rare in cats. Toxocara cati (33.0%) and Giardia (7.3%) were found more commonly. At least 1 zoonotic agent was detected in 105 samples (40.7%). Our results suggest that clinical signs such as diarrhea are not reliable predictors of whether a cat is actively shedding enteric organisms. Therefore, the decision to test a newly adopted cat should be based on the potential risks to the client rather than on the cat's clinical presentation. The high prevalence of T. cati confirms that comprehensive testing or treatment for ascarids is warranted in newly adopted kittens. PMID- 11215909 TI - Long-term clinical management of right-to-left ("reversed") patent ductus arteriosus in 3 dogs. AB - A small number of dogs with patent ductus arteriosus (PDA) have right-to-left flow of blood through the ductus, leading to polycythemia and clinical signs associated with hyperviscosity. Three dogs with right-to-left-shunting PDA are described. Treatment consisted solely of phlebotomy, performed on an outpatient basis when indicated by exacerbation of clinical signs, for a total of 11-68 times on each dog. Each treatment entailed the removal of a mean of 19% (maximum 28%) of circulating blood volume, divided into 2 phlebotomies several hours apart, without intravenous fluid replacement. Subjectively, marked clinical improvement was noted. Intermittent clinical signs decreased in frequency and severity in all dogs. Adverse effects were rare (1 for 98 phlebotomies) and reversible. Dogs lived > 2 to > 8 years during treatment. Outpatient phlebotomy without fluid replacement was safe, and was associated with subjective improvement and prolonged survival in these dogs. PMID- 11215910 TI - Equine basal cell tumors: 6 cases (1985-1999). AB - Basal cell tumors are rare benign tumors in horses. Over a 15-year period, 6 horses were diagnosed with basal cell tumors. The tumors were well-circumscribed. freely moveable, firm, raised papules, nodules, or masses that ranged from 0.6 to 5 cm in diameter. Five of the 6 tumors were ulcerated. Based on gross appearance, the tumors were diagnosed as sarcoids, and 1 was diagnosed as a melanoma. The range of age of affected horses was 6-26 years. The tumors were identified clinically 1 week to 3 years before excision. In 4 horses for which information was available, complete surgical excision was curative with no recurrence 4 months to 2 years after removal. PMID- 11215911 TI - Long-term health and predictors of survival for hyperthyroid cats treated with iodine 131. AB - Two hundred thirty-one cats treated with radioactive iodine at the Texas Veterinary Medical Teaching Hospital were followed for a median of 25 months by means of an ambidirectional (prospective, retrospective) cohort study design. Cox proportional hazards models were used to determine predictors of survival based on data at the time of hyperthyroid diagnosis (collected retrospectively) and found that only age at diagnosis and sex of the cat were predictors of survival. Increasing age (for each year of age, relative risk [RR] = 1.2, 95% confidence interval [CI] = 1.1-1.3) and being male (RR = 0.68, 95% CI = 0.5-0.9) increased likelihood of death. Tables predicting survival after diagnosis and treatment of hyperthyroidism for various age and sex combinations were created. In addition, Cox proportional hazard models were run with all data available at the end of the study (collected retrospectively and prospectively) including number and type of major health problems reported at the time of death or censoring. In this model, significant factors were age at diagnosis, sex, and either type of major health problem or number of health problems. Cats with renal disease or cancer were more likely not to survive and increasing from none to 2 health problems also decreased survival. Renal problems and cancer were the most common health problems at the time of death or censoring. This study provides estimates of duration of survival for cats successfully treated for hyperthyroidism with radioactive iodine, which can be useful in assisting with client treatment decisions. PMID- 11215912 TI - Diarrhea, diet, and diagnostics. PMID- 11215913 TI - Effect of amlodipine on echocardiographic variables in cats with systemic hypertension. AB - Left ventricular hypertrophy signals a poor prognosis in hypertensive humans. Cardiac disease is common in cats with systemic hypertension. The aims of this study were to characterize the echocardiographic findings of cats with systemic hypertension and to determine if reducing the degree of hypertension is associated with resolution of cardiac hypertrophy. Echocardiographic examinations were performed on 19 cats with naturally occurring systemic hypertension. Fourteen of these cats were subsequently studied after a minimum of 3 months of treatment with the antihypertensive agent amlodipine. Hypertensive cats had a significantly thicker interventricular septum in both systole and diastole, thicker left ventricular free wall in both systole and diastole, and larger left atrium compared to the published normal values and 74% (14/19) of the cats met criteria for left ventricular hypertrophy (diastolic septal or free-wall thickness > 0.60 cm). Systolic blood pressure was lower after treatment (217 +/- 25 mm Hg, range: 180-275 mm Hg; and 142 +/- 27 mm Hg, range: 90-200 mm Hg). No difference was found in any of the echocardiographic measurements between the untreated and treated cats, although more cats had ventricular hypertrophy before treatment (11/14) than after initiating amlodipine (6/14; P = .006). Ventricular hypertrophy is common in hypertensive cats and may resolve after the initiation of amlodipine. PMID- 11215914 TI - Common atrium in a dog. PMID- 11215915 TI - Clinical vignette. Von Willebrand disease in a Thoroughbred mare and foal. PMID- 11215916 TI - Food sensitivity in cats with chronic idiopathic gastrointestinal problems. AB - The objectives of this study were to investigate the prevalence of food sensitivity in cats with chronic idiopathic gastrointestinal problems, to identify the food ingredients responsible, and to characterize the clinical features. Seventy cats that presented for chronic gastrointestinal signs underwent diagnostic investigation. Fifty-five cats had idiopathic problems and were entered into the study. Diagnosis of food sensitivity was made by dietary elimination-challenge studies by using commercial selected-protein diets as the elimination diet. Sixteen (29%) of the 55 cats with chronic idiopathic gastrointestinal problems were diagnosed as food sensitive. The clinical signs of another 11 cats (20%) resolved on the elimination diet but did not recur after challenge with their previous diet. The foods or food ingredients responsible for the clinical signs were dietary staples. Fifty percent of affected cats were sensitive to more than 1 food ingredient. The clinical feature most suggestive of food sensitivity was concurrent occurrence of gastrointestinal and dermatological signs. Weight loss occurred in 11 of the affected cats, and large-bowel diarrhea was more common than small-bowel diarrhea. Assay of serum antigen-specific immunoglobulin E (IgE) had limited value as a screening test, and gastroscopic food sensitivity testing was not helpful. In conclusion, adverse reactions to dietary staples were common in this population of cats, and they responded well to selected-protein diets. Diagnosis requires dietary elimination-challenge trials and cannot be made on the basis of clinical signs, routine clinicopathological data, serum antigen-specific IgE assay, gastroscopic food sensitivity testing, or gastrointestinal biopsy. PMID- 11215917 TI - A system for determination of 3D vessel tree centerlines from biplane images. AB - With the increasing number and complexity of therapeutic coronary interventions, there is an increasing need for accurate quantitative measurements. These interventions and measurements may be facilitated by accurate and reproducible magnifications and orientations of the vessel structures, specifically by accurate 3D vascular tree centerlines. A number of methods have been proposed to calculate 3D vascular tree centerlines from biplane images. In general, the calculated magnifications and orientations are accurate to within approximately 1 3% and 2-5 degrees, respectively. Here, we present a complete system for determination of the 3D vessel centerlines from biplane angiograms without the use of a calibration object. Subsequent to indication of the vessel centerlines, the imaging geometry and 3D centerlines are calculated automatically and within approximately 2 min. The system was evaluated in terms of the intra- and inter user variations of the various calculated quantities. The reproducibilities obtained with this system are comparable to or better than the accuracies and reproducibilities quoted for other proposed methods. Based on these results and those reported in earlier studies, we believe that this system will provide accurate and reproducible vascular tree centerlines from biplane images while the patient is still on the table, and thereby will facilitate interventions and associated quantitative analyses of the vasculature. PMID- 11215918 TI - Quantification of 3-D coronary arterial motion using clinical biplane cineangiograms. AB - Speculation that the motion of the coronary arteries might be involved in the pathogenesis of coronary atherosclerosis has generated growing interest in the study of this motion. Accordingly, a system has been developed to quantify 3-D coronary arterial motion using clinical biplane cineangiograms. Exploiting the temporal continuity of sequential angiographic images, a template matching technique is designed to track the non-uniform frame-to-frame motion of coronary arteries without assuming that the vessels experience uniform axial strain. The implementation of the system is automated by a coarse-to-fine matching process, thus improving the efficiency and objectivity of motion analysis. The system has been validated and employed to characterize the in vivo motion dynamics of human coronary arteries; illustrative results show that this system is a promising tool for routine clinical and laboratory analysis of coronary arterial motion. PMID- 11215919 TI - Three-dimensional echocardiographic measurement of left ventricular mass: comparison with magnetic resonance imaging and two-dimensional echocardiographic determinations in man. AB - This study was performed to compare a novel three-dimensional echocardiography (3DE) system to clinical two-dimensional echocardiography (2DE) and magnetic resonance imaging (MRI) for determination of left ventricular mass (LVM) in humans. LVM is an independent predictor of cardiac morbidity and mortality. Echocardiography is the most widely used clinical method for assessment of LVM, as it is non-invasive, portable and relatively inexpensive. However, when measuring LVM, 2DE is limited by assumptions about ventricular shape which do not affect 3D echo. METHODS: A total of 25 unselected patients underwent 3DE, 2DE and MRI. Three-dimensional echo used a magnetic scanhead tracker allowing unrestricted selection and combination of images from multiple acoustic windows. Mass by quantitative 2DE was assessed using seven different geometric formulas. RESULTS: LVM by MRI ranged from 91 to 316 g. There was excellent agreement between 3DE and MRI (r = 0.99, SEE = 6.9 g). Quantitative 2D methods correlated well with but underestimated MRI (r = 0.84-0.92) with SEEs over threefold greater (22.5-30.8 g). Interobserver variation was 7.6% for 3DE vs. 17.7% for 2DE. CONCLUSIONS: LVM in humans can be measured accurately, relative to MRI, by transthoracic 3D echo using magnetic tracking. Compared to 2D echo, 3D echocardiography significantly improves accuracy and reproducibility. PMID- 11215920 TI - Stentless bioprostheses have ideal haemodynamics, even in the small aortic root. AB - OBJECTIVE: To determine normal Doppler and 2D gradients and flow characteristics of the Freestyle stentless aortic bioprosthesis related to valve size. BACKGROUND: The Freestyle stentless aortic bioprosthesis is one of the newer aortic xenografts. Only limited data are available of the echocardiographic flow characteristics during a mid-term follow-up period of this valve. Therefore valve performance related to valve size was measured during a follow-up period of two years. METHODS: 175 consecutive patients with a Freestyle aortic bioprosthesis underwent an echocardiographic and Doppler examination according to a common protocol. Investigations were done within 4 weeks after operation, after 3 to 6 months, and after 1 and 2 years. RESULTS: With a valve size from 19 to 27 mm mean gradients decreased from 8.0 +/- 5.1 mmHg at discharge to 5.8 +/- 3.8 mmHg after 3-6 months (p < 0.001). Thereafter gradients remained stable. The performance index, the ratio of the measured effective orifice area in the patient divided by the effective orifice area measured in vitro increased from 69 +/- 20% at discharge to 79 +/- 29% after one, two and three years. Performance index was especially very high in the smaller sized valves with a performance index of 85 +/- 17% for the 21 mm valve. During follow-up mean gradients remained below 10 mmHg even in the 21 mm valve. CONCLUSION: Stentless xenografts have ideal haemodynamics, even in the small aortic root. PMID- 11215921 TI - Reliability of mechanical and phased-array designs for serial intravascular ultrasound examinations--animal and clinical studies in stented and non-stented coronary arteries. AB - BACKGROUND: Both mechanical and multi-element intravascular ultrasound designs have potential advantages and limitations that may impact on their value for clinical and research purposes. Determination of the reproducibility of measurements is critical before a given system can be used in studies such as regression of atherosclerosis trials. METHODS: We performed serial intravascular ultrasound imaging with catheters using mechanical and phased-array designs in stented and non-stented coronary arteries in dogs and in patients. RESULTS: Both systems correlated well for areas (r > or = 0.90, p < 0.0001) and diameters (r > or = 0.84. p < 0.0001) in dogs and in patients. There was a slight difference between multi-element and mechanical designs for measurements of area (mean difference in dogs and in patients: -0.24 and 0.96 mm2, p < 0.055) and diameter ( 0.08 and 0.16 mm, p < 0.0001). The reproducibility of the multi-element system for reanalysis of the same frames and for analysis of serial pullbacks was similar to the same measurements with the mechanical system (r > or = 0.96 for all measurements). The differences in absolute and relative variability between the mechanical and phased-array designs, both for reanalysis of same frames and serial pullbacks, were very small. CONCLUSIONS: Although multi-element and mechanical intravascular ultrasound designs are not strictly interchangeable, their similar reproducibility and the small differences in measurements demonstrate that both designs are acceptable alternatives for trials of regression of atherosclerosis. Determination of the variability for serial pullbacks of both designs was also important to assess the statistical power of such trials. PMID- 11215922 TI - Cardiac thrombosis in a patient with Behcet's disease: two years follow-up. AB - A 28-year-old man with Behcet's disease was presented with cardiac symptoms in addition to previous complaints of oral and genital ulcers. A diagnosis of thrombosis was made and patient began to receive anticoagulant and immunosuppressive therapy and was followed by echocardiographic examination. Despite medical therapy, thrombosis recurred. Surgical excision was performed and histological findings were consistent with organizing thrombus. Nature of cardiac involvement and review of literature on cardiac thrombosis in Behcet's disease was discussed. PMID- 11215923 TI - A simple single slice method for measurement of left and right ventricular enlargement by electron beam tomography. AB - RATIONALE AND OBJECTIVE: We devised to test the feasibility of measuring the left and right ventricular sizes by non-contrast electron beam tomographic images. METHODS: Ventricular sizes consist of the sum of the intracavitary cavity and myocardial mass for each ventricle. A total of 50-image studies from subjects undergoing contrast-enhanced studies were used to develop the measurement methodology. About 20 contrast studies were used to test the measure. The methodology was then prospectively tested on 75 patients with non-contrast studies to estimate the intra-observer, inter-observer and inter-study reproducibility. RESULTS: Multiple linear regression analysis was completed and the correct regression formulas to calculate ventricular volumes were acquired by using the area and span from the contrast studies. There was excellent correlation between the estimate of LV (r > 0.97, p < 0.001) and RV (r > 0.93, p < 0.001) sizes between measured and calculated (contrast, single slice) left and right ventricular volumes. The intra-observer, inter-observer and inter-study reproducibility demonstrated excellent results with < 7% difference in absolute values and a high correlation (r > 0.89, p < 0.001). CONCLUSION: We conclude that the left and right ventricular sizes can be accurately estimated from a single mid-ventricular slice on non-contrast electron beam tomographic images. PMID- 11215924 TI - Accurate measures of left ventricular ejection fraction using electron beam tomography: a comparison with radionuclide angiography, and cine angiography. AB - BACKGROUND: Quantitative determination of ejection fraction is predicated on precise measurement of end-diastolic and end-systolic volumes of the left ventricle. Contrast enhanced electron beam tomography (EBT), with excellent temporal and spatial resolution, has the potential for highly accurate measures of ejection fraction. METHODS: EBT protocol used a short axis scan of the left ventricle (8-12 levels, apex to base) during infusion of iodinated contrast. To assess the accuracy of the measured left ventricular ejection fraction (LVEF), we compared EBT with first-pass radionuclide angiography (RNA) and cine angiography (CINE). RESULTS: A total of 41 patients (26 men and 15 women) underwent all three tests within 1 week. Resting ejection fraction using each modality was assessed in a linear regression model to assess inter-test correlation with the other two modalities. Correlation between CINE and EBT was high (r = 0.90, intercept 4.67, p < 0.001). Similarly, correlation of CINE and RNA (r = 0.87, intercept -5.48, p < 0.001) and between EBT and RNA (r = 0.87, intercept -4.6, p < 0.001) were high. In a subset of those patients with LVEF < or = 40%, correlation was consistently high between EBT and CINE. However, correlations were poor for the comparisons between RNA and CINE (r = 0.40), and between the RNA and EBT (r = 0.47). The mean differences of measured ejection fractions between each of the imaging modality were small. However, there was only modest agreement between each of the comparisons as measured using 95% confidence interval (CI) on Bland-Altman plots. CONCLUSION: These data indicate that the LVEF results are comparable among EBT, RNA, and CINE and can be used interchangeably to assess ventricular function for LVEF > 40%. For LVEF < or = 40%, we demonstrated some disparate results between cine angiography and RNA and between EBT and RNA, indicating that CINE or EBT may provide more accurate assessment. PMID- 11215925 TI - Safety of EBCT contrast injection studies in severe pulmonary hypertension. AB - PURPOSE: There is considerable literature published on noninvasive contrast enhanced techniques to diagnose pulmonary vascular abnormalities, however little data exists on the safety of contrast injections in patients with elevated pulmonary arterial pressures. We studied the safety of contrast-enhanced electron beam computed tomography (EBCT) in 29 patients with severe pulmonary hypertension. The mean dose of intravenous contrast used was 124 +/- 39 cc. MATERIALS AND METHODS: Subjects underwent EBCT using contrast injected at a rate of 2-4 ml/s. All patients were watched closely for at least 15 min post-procedure prior to being released. Patients had Doppler echocardiograms to estimate pulmonary artery pressure. Right heart catheterization data was collected for patients in which echocardiographic data was unavailable. RESULTS: A total of 29 patients with pulmonary arterial hypertension were studied. There were 17 patients with primary pulmonary hypertension (PPH), and 12 patients with secondary forms of pulmonary hypertension. None of the patients developed complications from their study. CONCLUSION: There is a paucity of data on the safety of contrast injections in patients with severely elevated pulmonary arterial pressures. Contrast-enhanced EBCT was well-tolerated in our diverse series of patients with severely elevated pulmonary arterial pressures. Clinicians concerned about invasive pulmonary angiography should consider contrast-enhanced EBCT as a safe alternative to angiography. PMID- 11215926 TI - Esophageal varices in congenital heart disease with total anomalous pulmonary venous connection. AB - Total anomalous pulmonary venous connection (TAPVC) is an uncommon congenital anomaly in which the anatomical presentations vary widely among patients. We hereby present two newborns with TAPVC associated with asplenia syndrome; both had severe esophageal varices due to infradiaphragmatic pulmonary venous drainage. Ultrafast computed tomography (CT) scanning was superior to color Doppler echocardiography and cardiac catheterization as it provided a detailed portrait of the pulmonary drainage. The remarkable radiographic manifestations are presented. PMID- 11215927 TI - [Nobel Prize in physiology or medicine 2000]. PMID- 11215928 TI - [Darwin in medicine]. PMID- 11215929 TI - [Is it possible to learn empathy?]. PMID- 11215930 TI - [Sons and fathers]. PMID- 11215931 TI - [Physicians as detectives]. PMID- 11215932 TI - [Personal responsibility and public control]. PMID- 11215933 TI - [Norwegian newspapers' presentation of Salmonella]. AB - BACKGROUND: Compared to other microbes, Salmonella gets rather frequent coverage in Norwegian newspapers. METHODS: This article reports a qualitative content analysis of three Norwegian newspapers' coverage of Salmonella in the period January 1996 to July 1998. We focus on aspects of the "risk image" given to Salmonella, with special emphasis on the type of solutions or measures that are associated with the Salmonella problem. RESULTS: The analysis shows that when a newspaper defines Salmonella as a potential risk in Norway, the responsibility and relevant solutions are placed mainly at the political and to some extent at the central administrative level. When Salmonella is defined as a current risk, there seems to be a shift to central and individual levels. With individual solutions the responsibility for Salmonella illness is placed at the consumers and their personal and food hygiene, and a relevant measure seems to be to educate the consumers to cope with the Salmonella risk themselves. INTERPRETATION: In Norway, Salmonella is a minor health problem compared to other countries. With the ongoing harmonisation between Norwegian and EU regulations, the Salmonella situation may change, and the relevant solutions may then imply a transfer of the responsibility for health to the individual. This raises the question of whether solutions based on individuals bearing responsibility for their personal health are desirable when it comes to such aspects as food, microbes and related risks. PMID- 11215934 TI - [Salmonella infection from turtles]. AB - Small turtles are asymptomatic carriers of Salmonella. Infants are particularly at risk of clinical infection. We describe an eight months old boy who became sick with Salmonella. The family had two turtles. Salmonella Abony was found in faeces from the child and in samples from both turtles. Commercial distribution of reptiles is prohibited in Norway. However, illegal import from other countries where no such ban exist is common. There are an estimated 10,000 pet reptiles in the Oslo region, most of them are turtles. More than 90% of turtles may be carriers of Salmonella. Many owners of turtles are not aware of the risk of salmonellosis from their pets. PMID- 11215935 TI - [Skin reaction after St Lucia holiday celebration]. AB - A 37-year-old man developed contact dermatitis on the front head after being exposed to dripping candles. The candles were placed in a crown on his head as he played St. Lucia in the traditional Lucia Day (13th December) pageant, trying to entertain the administrative staff of the University of Bergen where he was employed. Afterwards he washed his head with a soap he normally did not use. Probably the contact dermatitis is a skin reaction to the soap, but it is difficult to say whether the reaction was irritative or allergic. A similar case has not been reported earlier. It is of importance that noone stops celebrating the Lucia Day. However, proper precautions must be taken, with routines for avoiding exposure to stearine or unfamiliar soaps on the head of Lucia. PMID- 11215936 TI - [Fall from high altitude]. AB - BACKGROUND: It is controversial in which way the human body can tolerate mechanical stress and later develop sequelae after deceleration trauma. MATERIAL AND METHODS: A report on a 26-year-old male who survived a free fall of 28 metres from a building. RESULTS: It is accounted for an achieved velocity of 81 kph and accumulated energy of 21,000 Joule. The incident lead to multiple complicated fractures, nerve injuries and an acute head injury. The patient's cognitive function was restored after a few months, and he is satisfied with the outcome. PMID- 11215937 TI - [Are emergency admissions to medical departments dependent on weather?]. AB - BACKGROUND: It is widely believed that patients are more frequently admitted to hospital in bad weather. MATERIAL AND METHODS: We evaluated all 15,060 emergency admissions to the Medical Department of Rogaland Central Hospital during a 17 month period and compared this material with meteorological data. RESULTS: We found no correlation between the number of admissions and "good weather" (as defined by the amount of cloud cover), but we found a significant difference of about two more patients (6.6%) being admitted on days with rain and snow. There was no correlation between the amount of precipitation and the number of admitted patients, but a small, significant inverse relation between temperature and admissions. We have also demonstrated a considerable difference in the number of admissions on the different weekdays, with the highest number on Mondays and the lowest on Saturdays. INTERPRETATION: Both the incidence of disease and doctor availability may partially explain the influence of weather and the daily variation in emergency admissions to hospital. PMID- 11215938 TI - ["Now I am humble. Indeed." From Germany to Norway in 1934]. AB - A huge refugee problem arose when the Nazis came to power in Germany in 1933. The most acute stages were just after 1933 and from the summer of 1938. This refugee drama involved all the western countries, including Norway. This paper describes the fate of the German gynaecologist Hans Saenger (1884-1943), professor in Munich, who in 1933 was dispelled by the Nazis because of his Jewish descent. He fled to Norway in 1934 and settled in Fredrikstad. However, the attitude in Norway to refugees in general and Jews in particular was hostile, mainly because of fear of unemployment. Prejudice and xenophobia were of importance, also in the medical profession. PMID- 11215939 TI - [Help during the paratyfoid-A epidemic in Kirkenes in 1943-44]. AB - Finnmark is the northernmost county in Norway. Kirkenes played a prominent part in the Second World War, and suffered 328 Russian bombing raids. In June 1943, there was an outbreak of paratyphoid A in the town. Its water reservoirs were heavily contaminated from a camp for Russian prisoners of war. In November the situation became disastrous with 208 new cases. Six advanced medical students from Oslo and 16 volunteering Red Cross nurses were sent to Kirkenes for medical support. Their biggest problem turned out to be the large number of convalescent carriers excreting bacilli in the faeces. A provisional bacteriological laboratory was established. Almost the entire population of Sor-Varanger (10,000 inhabitants) was vaccinated with combined typhoid and paratyphoid A and B vaccine (TAB). The children were also vaccinated against diphtheria. Obviously the TAB vaccine did not protect against paratyphoid A. Officially, 254 Norwegian cases of paratyphoid A were registered in the course of the epidemic; the true number, however, was probably about 300. There was only one death, from intestinal perforation. PMID- 11215940 TI - [Smallpox in Telemark in the last part of the 19th century]. AB - Was vaccination the only cause of the decline of smallpox in Norway during the 19th century? This regional study focuses on the history of the disease in Telemark county with special emphasis on the last, extensive epidemic in 1868. In addition to vaccination, other possible causal relations are discussed. In Telemark, smallpox seems to have been relatively mild in the 19th century with the exception of the epidemics at the end of the 1830s and in 1868. In 1868 the disease spread along the main transportation routes northward through the western part and eastward through the more densely populated districts along the coast. The importance of vaccination is apparent from the fact that the municipalities with the lowest annual percentage of newborns vaccinated were most heavily struck by the epidemic. Despite vaccination procedures, both adults and unvaccinated children were groups at risk. Local initiatives--especially isolation and revaccination--largely prevented or restricted outbreaks of smallpox. It seems that the efforts of the district medical officers and local health administrators after 1860 were of decisive importance for the decline in smallpox cases in the period in question. PMID- 11215941 TI - [A matter of heart--two examinations of the same heart with a sixty year interval]. AB - The 20th of May 1869, Professor Emanuel Winge used a human heart as an exhibit at a meeting of The Medical Society in Christiania. This heart was later conserved and kept in the museum of the Institute of Pathology. Sixty years later, one of Winge's successors, Professor Francis Harbitz, used the very same heart, also at a meeting of The Medical Society. Harbitz had then confirmed Winge's hypothesis of 1869, that the endocarditis of this heart was due to a bacterial infection. This article contemplates the disparity between the "scientific gazes" of Winge and Harbitz, and why Harbitz was able to convert Winges hypothesis of 1869 into a scientific discovery in 1929. PMID- 11215942 TI - [Doctor Eyvind Kraft--halfway around the world in the 1880s]. AB - More than every second Norwegian 19th century physician made one or more study trips abroad. Some of them were probably more inspired by love of adventure than by the prospect of gaining new medical insight. This was probably also true of my great-grandfather, Eyvind Kraft. Shortly after completing medical school in 1879, he left Norway on the "Musca", an emigrant vessel, bound for Hawaii. He returned home approximately six years later to establish a sanatorium. In the meantime he worked as a ship's doctor, made a contribution to the understanding of the contagiousness of leprosy, and was among the founding members of the first medical society in the state of Wisconsin. Back in Norway he worked at the sanatorium, but also as a general practitioner and among fishermen during the seasonal fisheries. He had to travel to the Continent in an attempt to cure his "nerve disease". Eyvind Kraft's life tells an exciting story of exotic places and of the view of disease in his time. PMID- 11215943 TI - [Thomas H.Huxley--the naval doctor who became Darwin's bulldog]. AB - Thomas H. Huxley (1825-1895) was an English physician and biologist who had a deep impact on the Victorian age. More than any other at his time he introduced scientifically based values. As a member of London's school board he brought science into the curriculum, encouraging school-children to ask questions and to make their own observations. Huxley came from a lower middle class family with little money. By sheer determination and hard work he managed to get a medical education at Charing Cross Hospital Medical School. He then obtained a posting on H.M.S. Rattlesnake, which gave him a chance to explore the southern seas and to study marine species. The results were published by the Royal Society of which Huxley became a member at the age of 26, and later its president. After several years of uncertainty he secured a position at the Royal School of Mines, which he transformed into the Imperial College of Science. He was a prolific scientist with wide interests, doing valuable work in paleontology, taxonomy and ethnology. Huxley wrote numerous essays on philosophy and scientific subjects. He coined the word agnostic to explain his attitude to Christian dogma. His style was clear and direct, and his essays still read very well. However, Huxley is now mostly, perhaps unfairly, remembered for his defence of Darwin's theory of evolution. In his book Evidence as to man's place in nature, Huxley, in contrast to Darwin, deals with the evolution of humans, mainly based on comparative anatomy. Huxley advocated a firmly held belief that scientific truths will have a liberating effect on the minds of men. His lectures on scientific subjects attracted large audiences of people who had not had the benefit of a higher education. PMID- 11215944 TI - [From The Origin of Species to Artenes Oprindelse]. AB - The Origin of Species, Charles Darwin's most important work, was published in London in 1859. The first presentation in Norway, by P. Chr. Asbjornsen, appeared in the journal Budstikken. About 30 years passed before it was translated into Norwegian, and it took some time before Darwin's theories were debated in Norway. The zoologist Michael Sars introduced them in the Scientific Society in Christiania (i.e., Oslo) in 1869, but he was not met with a great deal of interest. However, a new generation of scientist saw this differently, mainly the botanist Axel Blytt, the zoologist G.O. Sars and the geologist W.C. Brogger. Two prominent professors of medicine were also involved in the debate, on different sides. The Darwinist Gerhard Henrik Armauer Hansen, who discovered the lepra bacillus, wrote several books and articles about Darwinism, while Professor Ernst Ferdinand Lochmann, though admiring Darwin as a prominent naturalist, strongly rejected Darwinism as a scientific theory. PMID- 11215945 TI - [The olfactory sense]. AB - BACKGROUND: In mammals, olfactory stimuli influence various aspects of life including feeding, social behaviour, and reproduction. METHODS: We review the progress in olfactory research in the last decade. RESULTS: In this era of gene based techniques, a breakthrough in our knowledge on odorant and pheromone detection has occurred. Most importantly, a large gene family of odorant receptors expressed in the olfactory epithelium has been discovered. Subsets of receptor cells express one and only one receptor type and send their axons to a corresponding glomerulus in the olfactory bulb, giving rise to an odor-specific map in this structure. Two gene families of pheromone receptors expressed in the vomeronasal organ have also been discovered, and a role of pheromones in mammalian reproduction has been established. INTERPRETATION: Although the crucial steps in odorant binding and transduction to nerve signals have been revealed, the central processing of this sensory information is basically unknown. Moreover, whether pheromones serve a significant role in human behaviour is still an open question. PMID- 11215946 TI - [Arne Thorkildsen and Thorkildsen's surgery]. AB - Arne Torkildsen (1899-1968) studied neurosurgery for one year at Queen Square and for four years (1930-34) with Wilder Penfield in Montreal. He returned to Oslo, Norway, in 1935 and took up responsibility for the neurosurgical section of the Department of Neurology of the National Hospital of Norway. In 1939, he introduced a new technique for operative treatment of hydrocephalus (ventriculocisternostomy, Torkildsen's shunt). His technique was the first successful procedure for shunting of cerebrospinal fluid and soon became internationally known and accepted as the standard operation for obstruction of the aqueduct or posterior third ventricle. In 1950, he defended his doctoral thesis at the University of Copenhagen, describing the technique and the results of the operation. He was professor of neurosurgery at the University of Cairo, Egypt 1951-1954. PMID- 11215947 TI - [Statins and muscular adverse effects]. PMID- 11215948 TI - [The "two cultures" in medicine]. AB - "The two cultures", a concept launched by C.P. Snow in 1959, points to the schism between science and the humanities, two distinct professional cultures which not only has gone separate ways, but also developed deep tensions between them. Historically, medicine is part of the scientific culture as well as that of the humanities. However, contemporary doctors see themselves first and foremost as scientists, and modern medicine leaves little scope for the tradition of the humanities. Including humanities in medical undergraduate, graduate and continuous education does not necessarily make doctors more humane, but insight in these disciplines may stimulate reflection and broaden their perspective on the practice of medicine. Given the expectations and pressures for efficiency to which doctors and other health care workers are subjected, a greater emphasis on the humanities in medicine may be of help to doctors in coping with their patients, society--and themselves. PMID- 11215949 TI - [What is the humanistic medicine?]. AB - At the Karolinska Institute, Stockholm's medical university, a new academic discipline was established in 1998. Humanistic medicine, or medical humanities, is a response to the need in an increasing technological medicine for a humanistic dimension in medical education and clinical practice. The mission of medical humanities is to contribute to the understanding of the scientific and ethical structure of medicine. Medical humanities should focus on clinical practice. At the Karolinska Institute, the discipline has three aspects: medical history, philosophy of medical science, and the "medical meeting", i.e. issues such as: What happens in the relation between patient and caregiver? What is the art of medicine? How is suffering and disease expressed in art and literature? Medical humanities can be a tool for critical reexamination and a radical reorientation of the ethos of medicine. After all, health care is at its very core a moral project. PMID- 11215950 TI - [Humanities and art as a part of medical education]. AB - From superstition and witchcraft, to detailed scientific insight into the human body in health and disease: Stupendous though the development of medical science has been over the last few centuries, it does not in itself give doctors a sufficient basis for meeting their patients and the people around them. In these interpersonal encounters, fundamental, immaterial values are the all-important basis. These values and their place in life are not visible in science itself, hence the humanities and the arts offer approaches and inspiration that are of the greatest value in the education of doctors at all levels. PMID- 11215951 TI - [The best available explanations]. AB - In 1959, C.P. Snow distinguished between the "two cultures"--the cultures of the natural and the human sciences. Medicine, however, does not and cannot belong to only one of these two cultures. It belongs essentially to both. The reason is that medicine is governed by certain ideals about what characterises a human life in dignity. These ideals define certain basic alternatives for action as immoral, for instance not to attempt to cure illness. This being so, there are certain phenomena which medicine cannot permit itself to ignore, thus it must seek the best available explanations of such phenomena where these explanations are to be found. Often the best explanations are to be found in the human sciences. Medicine needs concepts, theories and methods which enable its practitioners to grasp meaning, to describe social relations and to understand history. PMID- 11215952 TI - [The value basis of future medicine]. AB - The aim of this article is to propose a way of structuring the values that should constitute the basis of future medical practice, starting with the values that are common in contemporary medical practice. First, medicine must acknowledge that human worth is inviolable. This leads to activities aimed at strengthening autonomy as well as protecting the weak and vulnerable aspects of human life. Second, medicine must be based on sound professional practice. Medical knowledge should be developed by scientific means, but not only by biomedical methods. The fundamentally stochastic nature of medicine must be acknowledged. The third set of values relates to equity in the access to medical care. Services for the weakest among us should have high priority. Finally, medical practice has to be predictable and transparent. PMID- 11215954 TI - [Have you met Mao?]. AB - What is a clinical discourse, and what elements of the patient-doctor encounter are most important for the outcome in medical practice? I approach these questions by using the notion of narratology and some key concepts from discourse analysis: interaction, transaction and context. Traditionally, clinical discourse is either consultative or psychotherapeutic. I argue for a third approach to the patient-doctor discourse, a "narrative dialogue". In the narrative dialogue, the patient-doctor-interchange is supposed to be less structural, more flexible, more individualistic than what has traditionally been the case. The doctor is supposed to be visible as a person more than as a professional persona, and the patient is encouraged to participate in the dialogue with his or her own personal narrative as a substantial contribution to the consultation. PMID- 11215953 TI - [To see oneself in a context--medicine and historia--the two cultures]. AB - Historians and physicians have different social vantage points and have developed widely different professional cultures. This diversity is a distinct feature of their research, their theoretical approaches, and their scholarly methods. The historian's and the physician's points of view both seem to be necessary parts of medical history. The subject itself as well as the scholars involved may profit from teamwork. The author also asks whether historical knowledge in the field of medicine is useful for today's practitioners. Her answer is yes. Historical insight might contribute to a better understanding of day-to-day problems and the complex structures of which physicians are part. Furthermore, it is suggested that physicians will benefit from insights into why their discipline and their professional position have developed in the ways they have. At its best, historical knowledge can contribute to a deeper understanding of the limitations of medicine, and so may add to physicians' ability to adjust their role in line with the present time. Historical knowledge might even contribute to increased respect for other branches of knowledge and for other people's skills and professional problems. PMID- 11215955 TI - [What does a hospital building tell?]. AB - Hospital architecture may be seen as an artistic expression and interpreted as such. In general, architecture is more dependent than other form of art on external forces: The requested function of the building normally puts important constraints on the implementation of architectural ideas. In addition, buildings are often rebuilt and altered in ways that make a retrospective analysis of the basic ideas behind them difficult. Hospital buildings usually reflect the state of the art of medicine at the time of construction or reconstruction, and their architecture should be interpreted in the light of the medical setting of the time. Other elements and influences, such as general views on health and sickness, religion, economy, style etc. should also be taken into consideration. This article discusses examples that show some of the possible pitfalls when we attempt to give a cultural interpretation of hospital buildings. The conflict between charity and rationality seems to be a basic problem in modern hospitals, an example is given where this conflict is reflected in the architecture. PMID- 11215956 TI - [Pleasure of reading through the forehead mirror]. AB - Doctors need not put aside their scientific curiosity when reading fiction. The search for medical matters in fiction does not put a constraint on the appreciation of literature; it may, in fact, add to the pleasure of reading. This article presents some examples of how novelists use medical matters. Unexpected medical information may be found, and authors' portrayal of doctors as heroes or villains may set off new trains of thought in the reading physician. The pleasures of reading and discovering may benefit doctors as well as patients. PMID- 11215957 TI - [The human face of medicine--the visual art]. AB - This article discusses the role of art in medicine on the background of experience with art lectures for medical students and courses and exhibitions for doctors. From the last half of the 19th century, Norwegian artists have taken an interest in medical themes. Their paintings are an important contribution to medical history in Norway; more generally, they contribute to our understanding of the development of Norwegian society. Visual art is an important element in the decoration of hospitals. The works on display in the new National Hospital buildings in Oslo show how art may successfully be used in indoor as well as outdoor areas. It is important to let artists in on the planning process prior to the building of a new hospital. PMID- 11215958 TI - [Is there a place for humanistic dimension in medical education?]. AB - Inspired by the concept of "two cultures", coined by C.P. Snow, this paper discusses the role of the humanities in relation to the natural sciences in a recently (since 1993) revised medical curriculum at the Faculty of Medicine in Trondheim, Norway. A concept of a "third culture" is identified as well: community medicine in a broad sense, disciplines dealing with health, illness and disease in the context of society and the environment. The implementation of the new curriculum was affected by intended and unintended social forces. The result was a hybrid model rather than the planned "pure" problem-based model. The humanities and "third culture" disciplines tended to yield to the pressure from the basic sciences when numbers of formal lectures were strictly limited, while the basic sciences themselves felt cut short by clinical disciplines. Problem based learning in groups did seem efficient in basic sciences and clinical subjects, but not for the humanities or third culture disciplines. This apparent limitation in the problem-based approach was probably due to contextual factors, rather than inherent in the method itself. PMID- 11215959 TI - [How to teach ballet to a swat?]. AB - There is increasing interest in including humanities subjects in the medical curriculum, as a means of accelerating students' personal development and of helping them in their meeting with patients, in order to counteract a perceived communication deficit in the health care system. Traditionally, medical schools have favoured students who concentrate on what is most relevant for their exams, possibly at the expense of reflection, idealism and empathy. As medical students in the University of Oslo, we do not feel that the situation is as bad as some claim it is. Most medical students have a wide range of ability and show interest and involvement in their own as well as their patients' situation. Humanities subjects are included in the curriculum, but it is tempting to see them as "spice" added for flavour and spread out over the course with no clear logic behind it. We do not necessarily see the need for more humanities courses, but we do see a need for more critical evaluation of what is taught. Humanities in the medical education should aim not just at improving communication skills, they should also include perspectives on how health care professionals can take of themselves, and put medicine into a wider scientific and historical perspective. PMID- 11215960 TI - [Sigmoid Freud and Harald Schjelderup--views on telepathy and parapsychology]. PMID- 11215961 TI - [Oskar Pfister as psychotherapist of the brothers Kristian and Harald Schjelderup]. PMID- 11215962 TI - [The Amish people and the simple life--glimpses from the history, society and health of a religious minority]. PMID- 11215963 TI - [To be on call during the New Year's Eve]. PMID- 11215964 TI - [To commit, to make or to take suicide--changing language norm]. PMID- 11215965 TI - [Legionella pneumonia]. PMID- 11215966 TI - [Oxytocin prevention in labor]. PMID- 11215967 TI - [To get a premature baby]. PMID- 11215968 TI - [Maintenance treatment of opiate addicts]. PMID- 11215969 TI - [You are dead--but your personal integrity is still alive]. PMID- 11215970 TI - [Is the era of general practice over?]. PMID- 11215971 TI - Risk factors for Alzheimer's disease. PMID- 11215972 TI - Alzheimer's. Dispelling the myths (a personal view). PMID- 11215973 TI - Stoma surgery in the older adult. AB - In this article Barbara Stuchfield discusses the care of the older adult undergoing stoma-forming surgery, and outlines the assessments and postoperative care that should be undertaken by nurses. PMID- 11215974 TI - Assessing older people. PMID- 11215975 TI - That was the year that was. PMID- 11215976 TI - Guiding continence care. PMID- 11215977 TI - Skin care for older people with incontinence. PMID- 11215978 TI - Old age in today's Britain. PMID- 11215979 TI - Quality care: the inside story. PMID- 11215980 TI - Enhancing family therapy: the addition of a community resource specialist. PMID- 11215981 TI - Approaches to the study of gender in marriage and family therapy curricula. AB - This study compares two accredited marriage and family therapy programs: One includes a separate course on gender, and the other integrates gender throughout the curriculum. Students from the two programs rated their own and their peers' experience of how gender education effects therapy, program culture, and personal life. Results indicate that students from the integrated program view their peers as incorporating gender ideas in therapy to a significantly greater extent (t = 2.83, p < .05) than do students in the gender course program. However, students from the program that has a gender course leaned more toward agreement with feminist concepts than did students from the integrated program. Overall, students appear to be learning about gender and integrating these concepts into their work as therapists. Discussion is included on how to choose a gender curriculum. PMID- 11215982 TI - Teaching family therapists about sexual attraction in therapy. PMID- 11215983 TI - Clients' views of live supervision and satisfaction with therapy. AB - In this study we examined clients' perceptions of live supervision and their satisfaction with therapy in a university-based training clinic for marriage and family therapists. A total of 108 clients completed the Client Satisfaction Questionnaire-8 and a modified version of the Purdue Live Observation Satisfaction Scale. Clients' comments on the advantages and disadvantages of live supervision were also solicited through short-answer questions. Results indicated that clients were generally satisfied with therapy and found the live-supervision process satisfactory as long as the perceived helpfulness of live supervision outweighed its perceived intrusiveness. The challenge for training clinics is striking a balance between helpfulness and intrusiveness in an effort to both train competent therapists and provide quality treatment. PMID- 11215984 TI - All those in favor of saving the planet, please raise your hand: a comment about "family therapy saves the planet". PMID- 11215985 TI - Healing the world in fifty-minute intervals: a response to "family therapy saves the planet". PMID- 11215986 TI - Saving the planet--or ourselves? PMID- 11215987 TI - Reconstituting racial histories and identities: the narratives of interracial couples. AB - This study explores the process by which interracial spouses construct narratives about their racial histories, identities, and experiences in their relationship together. Ten black-white couples were interviewed individually and conjointly. The results reflected interracial spouses' experience of their life together, their perception of others' perceptions of them, and their unique processes of negotiating racial, gender, and class differences. Black spouses, compared with white spouses, demonstrated a greater awareness of and sensitivity to social resistance to interracial couples, and black spouses' familial and personal histories were sometimes relegated to silence in the couple relationship. I discuss recommendations for marriage and family therapists working with interracial spouses. PMID- 11215988 TI - Family therapy saves the planet: messianic tendencies in the family systems literature. AB - It is not unusual occasionally to hear individual family therapists describe their work as an effort to "save the world." The messianic notion that family therapy should be the world's salvation is not simply a fancy of individual clinicians, but is deeply imbedded in several of our field's most fundamental theories. This article explores messianic arguments in the work of some of family therapy's most important thinkers, including von Bertalanffy, Bateson, and Keeney, and then discusses the implications that these arguments have for the clinical and theoretical development of our field. PMID- 11215989 TI - Developing culturally competent marriage and family therapists: guidelines for working with Hispanic families. AB - As the Hispanic population of the United States continues to grow, so will the need for therapists who have been trained to work with Hispanic families. This content analysis of the available treatment literature generated several specific guidelines that can be used in training and evaluating culturally competent therapists. Guidelines included: Use family therapy, act as advocate for the family, assess immigration experience, assess acculturation, respect father, interview family subsystems separately, do not force changes, provide concrete suggestions, and warmly engage the family. Empirical and conceptual support for each guideline is discussed and several conclusions are made regarding culturally competent therapy with Hispanic families. PMID- 11215990 TI - Mars and Venus: unequal planets. AB - Self-help books, a pervasive and influential aspect of society, can have a beneficial or detrimental effect on the therapeutic process. This article describes a thematic analysis and feminist critique of the best-selling self-help book, Men are from Mars, Women are from Venus. This analysis revealed that the author's materials are inconsistent with significant family therapy research findings and key principles of feminist theories. His descriptions of each gender and his recommendations for improving relationships serve to endorse and encourage power differentials between women and men. PMID- 11215991 TI - The feminist/emotionally focused therapy practice model: an integrated approach for couple therapy. AB - Emotionally focused therapy (EFT) is a well-developed, empirically tested practice model for couple therapy that integrates systems, experiential, and attachment theories. Feminist family therapy theory has provided a critique of biased assumptions about gender at play in traditional family therapy practice and the historical absence of discussions of power in family therapy theory. This article presents an integrated feminist/EFT practice model for use in couple therapy, using a case from practice to illustrate key concepts. Broadly, the integrated model addresses gender roles and individual emotional experience using a systemic framework for understanding couple interaction. The model provides practitioners with a sophisticated, comprehensive, and relevant practice approach for working with the issues and challenges emerging for contemporary heterosexual couples. PMID- 11215992 TI - Methods of feminist family therapy supervision. AB - Although feminist family therapy has been studied and practiced for more than 20 years, writing about feminist supervision in family therapy has been limited. Three supervision methods emerged from a qualitative study of the experiences of feminist family therapy supervisors and the therapists they supervised: The supervision contract, collaborative methods, and hierarchical methods. In addition to a description of the participants' experiences of these methods, we discuss their fit with previous theoretical descriptions of feminist supervision and offer suggestions for future research. PMID- 11215993 TI - Couples therapy for women survivors of child sexual abuse who are in addictions recovery: a comparative case study of treatment process and outcome. AB - Treatment for women who are survivors of child sexual abuse and who have a history of substance abuse has largely involved gender-specific interventions. This study examines the use of conjoint couple therapy with a cohort of women who were survivors of child sexual abuse and who are in addiction recovery and with their partners. A comparative case study analysis incorporated standardized clinical measures with client and therapist interviews. Brief conjoint therapy was found to assist couples in the specific relationship skill areas of communication and mutual problem solving. Further, substantive gains were found in the realm of affective relations. The women reported an increase in support from their male partners, and the men reported a decrease in negative emotional atmosphere in the relationship. PMID- 11215994 TI - The relative buffering capacities of saliva and moist snuff: implications for nicotine absorption. AB - Commercial moist snuff products are used by placing a portion of tobacco inside the mouth between the inner cheek or lip and gum. Nicotine is absorbed into the blood stream via transfer across various oral membranes including the buccal mucosa (cheek lining). The resulting salivary pH when a given moist snuff product is placed in the mouth is an important factor for nicotine absorption because it will affect the proportion of free base nicotine that is readily available for absorption. The resulting salivary pH for a given moist snuff product will be determined in part by the relative acid-base buffering capacities of the saliva and moist snuff, as well as the pHs of the saliva and moist snuff prior to coming in contact with one another. In the current study, the acid-base buffering capacities (mu eq/g) of a series of commercial moist snuff products were determined and compared to the acid-base buffering capacity for unstimulated, whole human saliva. The buffering capacities of the moist snuff products were determined to be 10-20 times higher than the buffering capacity of human saliva. The resulting salivary pH ranges after contact between an artifical saliva and the various moist snuff products were also determined; the results were used to predict the proportion of free base nicotine that can be expected to occur in the mouth during the first few minutes of product use. These studies provide a basis for examining and understanding the effects that moist snuff product pHs and buffering capacities may be expected to have on nicotine absorption. PMID- 11215995 TI - Stability of morphine, morphine-3-glucuronide, and morphine-6-glucuronide in fresh blood and plasma and postmortem blood samples. AB - The present study was designed to determine the stability of morphine and its glucuronides in spiked fresh blood and plasma from live individuals as well as in four authentic postmortem blood specimens for a time interval of up to six months. The samples were stored in glass vials at -20 degrees C, 4 degrees C, and 20 degrees C. Additionally, spiked samples were exposed to light through window glass and subjected to a forced-degradation study at 40 degrees C. Data were established using solid-phase extraction and high-performance liquid chromatography coupled to atmospheric pressure ionization mass spectrometry for isolation and quantitation, providing a sensitive and specific detection method for the parent drug in the presence of its glucuronide metabolites. Morphine and its glucuronide metabolites were found to be stable in both blood and plasma at 4 degrees C for the whole observation period. In postmortem blood the analytes were stable only when stored at -20 degrees C. The thermal decomposition of morphine and morphine-6-glucuronide in spiked blood and plasma could be interpreted using pseudo first-order kinetics. Photodegradation of morphine-3-glucuronide in plasma was consistent with a second-order reaction. In postmortem samples the degradation pattern differed completely from that observed in fresh blood and plasma. The elevated morphine levels observed were primarily due to postmortem hydrolysis of morphine glucuronides. PMID- 11215996 TI - FT-IR breath test in the diagnosis and control of treatment of methanol intoxications. AB - A portable Fourier transform infrared (FT-IR) multicomponent point-of-care analyzer was tested for the diagnosis of methanol intoxications. Breath analysis with FT-IR was fast and easy, and no sample preparation was needed. The analyzer was adequately sensitive and accurate in detecting and quantitating clinically relevant amounts of ethanol and methanol in the breath of seriously ill patients. FT-IR spectrometry was also suitable for nearly on-line monitoring of the exhaled ethanol and methanol during hemodialysis. The breath analysis results correlated well with blood samples. The FT-IR method used also has a traceable calibration to physical properties of the analyte, and the measured spectra can be saved for later analysis. PMID- 11215997 TI - Detection and quantitation of morphine in fixed tissues and formalin solutions. AB - The study reports the results of the detection and quantitation of morphine in tissues fixed in formalin and in the formalin solutions in which the same tissues were fixed. Toxicological analyses were performed on formalin-fixed liver and kidney samples from five cases of opiate poisoning and on the formalin solutions (10% buffered pH 7) in which the samples were preserved. Analyses carried out at the time of autopsy on body fluids and tissues allowed identification of opiate as the cause of death and its quantitation. Tissue samples were preserved in formalin solutions for 12 weeks before analysis. The mean levels of recovery of morphine in fixed tissues were 36.29% in liver, 29.41% in kidney, 74.93% in formalin from liver, and 42.17% in formalin from kidney. Results indicated that this particular toxic substance shows good stability even in biological specimens subjected to chemical fixation. PMID- 11215998 TI - Simultaneous determination of 2,4-D and MCPA in canine plasma and urine by HPLC with fluorescence detection using 9-anthryldiazomethane (ADAM). AB - A method for the simultaneous determination of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2-methyl-4-chlorophenoxyacetic acid (MCPA) in canine plasma and urine has been developed. This method used derivatization of extracted samples with 9 anthrylmethane (ADAM) for analysis by reversed-phase high-performance liquid chromatography with fluorescence detection. Precision and accuracy were within the accepted limits of 15% and 85-115%, respectively, for both analytes in plasma and urine. Calibration curves for 2,4-D and MCPA in plasma were linear (r2 > 0.99) between 0.50 and 5.0 mg/L and 5.0 and 100 mg/L. Calibration curves for 2,4 D and MCPA in urine were linear (r2 > 0.99) between 5.0 and 70.0 mg 2,4-D/L and 10.0 and 70.0 mg MCPA/L. The lower limit of detection was 62.5 ng/mL for both 2,4 D and MCPA. PMID- 11215999 TI - Analysis of methadone and its metabolites in meconium by enzyme immunoassay (EMIT) and GC-MS. AB - An EMIT-ETS d.a.u. immunoassay screening method for methadone in meconium and a gas chromatography-mass spectrometry (GC-MS) method for methadone and its metabolites including 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenylpyrroline (EMDP) in meconium were described. The GC-MS method showed good linearity (r2 > or = 0.998) over a concentration range of 25-2000 ng/g with limits of detection of 10, 25, and 10 ng/g for methadone, EDDP, and EMDP, respectively, and a limit of quantitation of 25 ng/g for all three analytes. Fifty pooled meconium samples were screened using a cutoff of 200 ng/g, and all samples screened negative. GC-MS analysis of all samples showed four samples to contain methadone (35.2 to 79.9 ng/g), EDDP (28.5 to 557.2 ng/g), or both, with no detectable amount of EMDP. The negative results on the four specimens at the cutoff used may be explained by the fact that EMIT-ETS d.a.u. antibody for methadone was specific to the parent drug. The results point to the fact that immunoassays should be directed to EDDP for detection of prenatal exposure of methadone through analysis of meconium specimens. PMID- 11216000 TI - Computer-aided screening for hallucinogenic and stimulant amphetamines with gas chromatography-Fourier transform infrared spectroscopy (GC-FTIR). AB - An expert system applied as a screening test for amphetamine analogues found in recreational-drug exhibits (tablets or powders) is described. The knowledge base defining the reference Fourier transform infrared spectroscopic (FTIR) spectral patterns has been built according to criteria encompassing toxicological, pharmacological, and neurochemical aspects. The class identity of a compound is determined within seconds using soft independent modeling of class analogy (SIMCA). The predictive value of the system, as assessed at a testing accuracy of 95%, is expressed by a total correct classification rate of 93.93% and by a 96.30% rate of true-positive amphetamines. The specificity and the selectivity of the screening test, evaluated by testing 159 toxicologically relevant compounds, are discussed, emphasizing the chemical and physical factors affecting these parameters. Medicinal amphetamines giving cross-reactions with traditional screening techniques produce a negative result. The specificity of the system characterizes the expert system as a highly sensitive, selective, fast, and user friendly screening test that screens for amphetamines with prediction accuracy adequate for investigations in analytical toxicology. PMID- 11216001 TI - Bioanalysis of the enantiomers of (+/-)-sarin using automated thermal cold-trap injection combined with two-dimensional gas chromatography. AB - A fully automated multidimensional gas chromatographic system with thermal desorption injection and alkali flame detection was developed for analysis of the enantiomers of the nerve agent (+/-)-sarin. The chiral stationary phase was CP Cyclodex B on which the sarin enantiomers were completely resolved. The absolute detection limit was 2.5 pg per enantiomer. The method is intended to be used for the analysis of the sarin enantiomers in biological samples. For this purpose, sarin was isolated from guinea pig blood via solid-phase extraction. Deuterated sarin was used as internal standard. Stabilization of sarin in the blood sample by acidification and addition of an excess of a competitive organophosphorus compound (neopentyl sarin) appeared to be essential. The absolute recovery of the extraction procedure was 60%, whereas the recovery relative to the internal standard was 100%. PMID- 11216002 TI - Immunoassay for detection of cocaine/metabolites in oral fluids. AB - There is growing interest in the use of alternate biological fluids for drug testing. An advantage of oral fluids is that collection can be made from individuals under direct observation without undue embarrassment or invasion of privacy. This study evaluated the STC Cocaine Metabolite MICRO-PLATE EIA for use in detection of cocaine and metabolites in oral fluids. Intra- and interassay precision of the EIA was < 10%. The EIA was cross-reactive to benzoylecgonine (100%), cocaine (> 12.9%), and cocaethylene (13.8%), but did not demonstrate detectable cross-reactivity with other commonly encountered medicants. Evaluation of a series of potential adulterants of oral fluids indicated that common household chemicals and foodstuffs did not alter the outcome of EIA testing for cocaine metabolite. Analysis by EIA and by gas chromatography-mass spectrometry (GC-MS) of oral fluids and urine specimens collected from current drug users in treatment programs and subjects participating in research studies involving controlled dosing of cocaine provided assessment of the clinical sensitivity and specificity of the STC Cocaine Metabolite EIA. Analysis of the data by means of receiver operating characteristic (ROC) plot indicated that the optimal cutoff concentration for the oral fluids EIA was 10 ng/mL. In comparison to GC-MS (10 ng/mL combined cutoff concentration for cocaine and benzoyleogonine), the EIA (10 ng/mL cutoff concentration) demonstrated a sensitivity, specificity, and accuracy of 95%, 82%, and 88%, respectively. The oral fluids EIA was slightly less sensitive than the urine EIA (300-ng/mL cutoff concentration) for the detection of cocaine metabolite with a sensitivity, specificity, and accuracy of 73%, 85%, and 88%, respectively. Overall, testing of oral fluids for cocaine metabolite with the STC Cocaine Metabolite MICRO-PLATE EIA appears to offer a viable alternative to urine for detection of recent cocaine use. PMID- 11216003 TI - Rapid confirmation/quantitation of ecgonine methyl ester, benzoylecgonine, and cocaine in urine using on-line extraction coupled with fast HPLC and tandem mass spectrometry. AB - A rapid, rugged, and highly specific assay for the quantitation of cocaine (COC) and especially its primary metabolites benzoylecgonine (BZE) and ecgonine methyl ester (EME) in human urine has been established. Here, we investigated the use of on-line sample extraction coupled to rapid chromatography systems for tandem mass analysis of COC, EME, and BZE in human urine. Using this method, sample preparation consisted of a sole centrifugation step. Combined extraction and chromatographic run times were < 3.5 min. The lower limits of detection were 0.5 ng/mL, 2.0 ng/mL, and 0.5 ng/mL for EME, BZE, and COC, respectively. Linear calibration curves ranging from 7.5 ng/mL to 1000 ng/mL were produced for the test analytes. Within-day and between-day precision and accuracy of the assay were determined using human urine quality-control specimens at 5, 10, or 15; 150; and 1000 ng/mL. The analyses were performed over the course of five days, rendering %CVs < 10% for EME, BZE, and COC. Percent mean accuracy for the three analytes of 97 to 113% were obtained. Our data suggest that on-line sample extraction coupled with rapid high-performance liquid chromatography-tandem mass spectrometry may be a viable alternative for EME, BZE, and COC analyses in human urine. PMID- 11216004 TI - A mass spectrometric method for quantitation of intact insulin in blood samples. AB - An analytical method was developed for the quantitation of intact insulin in blood samples. Solid-phase extraction (SPE) was used to purify and concentrate the protein after the plasma is separated. Analysis is performed by electrospray liquid chromatography-mass spectrometry (LC-MS) using a trifluoroacetic acid mobile phase. The limit of quantitation of the SPE LC-MS method has been determined to be 1.0 ng/mL for endogenous levels of insulin. Base levels of human insulin in plasma have been quantitated, and values ranging from 1.0 to 1.4 ng/mL were observed. In a single analysis, the method can determine human, porcine, and bovine insulin. Reproducibility was tested for both blood samples and aqueous standards and produced relative standard deviations of approximately 10% and lower. Calibration curves were constructed corresponding to plasma levels of 0.4 to 80 ng/mL and found to be linear with R2 values greater than 0.99. Stability studies of human and porcine insulin were performed over a period of 21 days for whole human blood samples stored at both room temperature and 4 degrees C. Hemolyzed blood samples were also analyzed using the developed method and were found to produce quantitatable levels of insulin. The advantage of the application of SPE and LC-MS for the quantitation of insulin is the high specificity compared to other techniques such as radioimmunoassay (RIA). In addition, the developed LC-MS method is not subject to interferences that cause problems with RIA, such as hemolysis. The method is efficient and rapid and produces results more specific than those obtained with RIA. PMID- 11216005 TI - [High rate of recurrence, misplaced surgical mesh. Technical errors in hernia surgery? (interview by Petra Eiden)]. PMID- 11216006 TI - [Botulinum toxin also has an analgesic effect. Nerve poison against headache]. PMID- 11216007 TI - [The best nutrition for the brain. Can one become intelligent by eating?]. PMID- 11216008 TI - [Nodules in the thyroid gland. What is important in suspected carcinoma]. PMID- 11216009 TI - [Thyroid carcinoma. Diagnosis--nonoperative therapy--after care]. AB - Thyroid carcinomas may originate in the thyroid cells (follicular and papillary, carcinoma, so-called differentiated carcinomas, constituting roughly 80-90% of cases), and the calcitonin-producing parafollicular C cells (medullary carcinoma, roughly 10%). The suspected diagnosis is clarified with the aid of ultrasonography, scintigraphy and fine-needle aspiration cytology. Primarily, carcinomas of the thyroid are treated surgically; in the case of differentiated carcinomas, surgery is followed by radio-iodine treatment, and in the follow-up period 131I scintigraphy is performed. During this period, physical examination, ultrasonography of the neck, monitoring of the tumours markers, and treatment with levothyroxine are applied (TSH-suppressive in cases of differentiated carcinoma). In the event of a recurrence showing rapid progression, when surgical and nuclear medical treatment modalities have been exhausted, chemotherapy can be given. PMID- 11216010 TI - [When is total thyroidectomy indicated? What applies in thyroid carcinoma: radical surgery according to findings]. AB - Today, surgical treatment of thyroid carcinoma is oriented to the underlying histology and the extent of the tumourous process. Total thyroidectomy with postoperative radioiodine treatment represents only one of the spectrum of possibilities that ranges from limited to extended radical interventional procedures. Such an individualized operative strategy should be applied not only for the primary intervention, but also for locoregional tumour recurrence and confirmed distant metastases, with the aim of keeping operative morbidity to a minimum. PMID- 11216011 TI - [Ulcer therapy with a new proton pump inhibitor. One week of treatment is enough]. PMID- 11216012 TI - [Not vaccinated--pneumococci become life threatening. Case report of pneumonia requiring artificial respiration]. PMID- 11216013 TI - [Diabetic food syndrome. Angiologic diagnosis and therapy]. PMID- 11216014 TI - [The post-infarction patient. When anxiety handicaps daily life]. PMID- 11216015 TI - [Diagnostic quiz. A sclerosed vertebral body. Paget disease]. PMID- 11216016 TI - [Non-cardiac vascular surgery. Perioperative beta blockade protects the heart]. PMID- 11216017 TI - [Fasting blood glucose has little value. Postprandial glucose indicates risk]. PMID- 11216018 TI - [Germany as an island? Depression: America manages differently]. PMID- 11216019 TI - [Approaching Western scientific standards. Learning acupuncture in Peking]. PMID- 11216020 TI - [Violence against physicians. Colleagues, who are assaulted, are behaving wrong]. PMID- 11216021 TI - Joint replacement. Help for when pain changes your lifestyle. PMID- 11216022 TI - Can telehealth technology be used for the education of health professionals? AB - The purpose of this report is to describe the usefulness and desirability of using telehealth technology in the education of health care professionals. The PC compatible, Windows-based system allowed for both real-time videoconferencing and store-and-forward (sending information from one site and stored at a distant site for access at a later time) functions. Student responses indicated that they thought they would benefit from this type of technology in their clinical education. They were most positive with respect to increasing access to a wider range of clients they may not otherwise access and least positive for the ability to learn from a televideo interaction when compared with a clinic experience. Similarly, faculty were least interested in using videoconferencing for patient rounds and more interested in using telehealth to enhance classroom presentations. PMID- 11216023 TI - The experience of caring for a family member with Alzheimer's disease. AB - The purpose of this phenomenological study was to describe the experience of caring for a family member with Alzheimer's disease or related disorder (ADRD) living at home among a diverse sample of 103 family caregivers. The study involved secondary analysis of in-depth transcribed interview data using van Kaam's rigorous four phase, 12-step psychophenomenological method. A total of 2,115 descriptive expressions were categorized into 38 preliminary structural elements. Eight essential structural elements emerged from an analysis of the preliminary structural elements. The eight elements were then synthesized to form the following synthetic structural definition: Caring for a family member living at home with ADRD was experienced as "being immersed in caregiving; enduring stress and frustration; suffering through the losses; integrating ADRD into our lives and preserving integrity; gathering support; moving with continuous change; and finding meaning and joy." PMID- 11216024 TI - Violence on TV and aggression in children. PMID- 11216025 TI - Evaluation of a home health patient classification instrument. AB - The purpose of this study was to assess reliability and validity of the Revised Easley-Storfjell Patient Classification Instrument (R-ESPCI). Content validity was assessed by expert home health nurses. Interrater reliability was assessed by staff nurse ratings of patients on home visits (N = 34) and by chart review by the investigators (N = 30). Concurrent validity was also assessed. Percentage agreement for staff nurses was 36% (kappa = -.15) and 52% (kappa = .04) in two phases and for investigators 90% (kappa = .63) and 50% (kappa = .02) in two phases. Minimal support for concurrent validity was found. Content validity was established, but revised reimbursement policy eliminated less acutely ill patients, narrowing the acuity range. More discrete rating criteria or scoring changes may be needed, followed by further assessment of the R-ESPCI. Agency stability and adequate resources for staff training are required for additional testing of the instrument. PMID- 11216026 TI - The created environment for physical assessment by case managers. AB - Goals of gerontological nursing include maximizing health and confronting functional impairments. The health of older adults is often fragile because of age-related change, complicated by chronic illnesses. Identification of changes in health status permits responsive care and consultation but requires proficiency in physical assessment. In 1995, research was conducted in Alberta, Canada, on registered nurse case managers' reported use of assessment skills. Nineteen continuing-care facilities in 1 of 17 provincial health regions participated (N = 189). After expert review and pilot testing, questionnaires were distributed to two independent groups: nurse administrators/staff development coordinators and case managers (response rate = 73%). Qualitative data were subjected to descriptive, interpretive, and pattern coding. Reported are factors constraining or facilitating physical assessment in continuing care. Neuman's concept of the created environment provided a factor-organizing framework. A holistic view of environment and data source triangulation increased confidence in the comprehensiveness and credibility of results. PMID- 11216027 TI - Measuring adherence to a women's walking program. AB - The purpose of this study is to demonstrate the use of a self-report exercise log and a heart-rate monitor in the measurement of adherence to the dimensions of an exercise prescription and to propose an alternative way to define adherence to a 24-week home-based women's walking program, which reflects the dynamic process of behavior change. Adherence was measured with exercise logs, Polar Vantage XL Heart-Rate Monitors, and pre- to postintervention change in VO2 max. Of the dimensions of the exercise prescription, frequency of walks documented by both the heart-rate monitor and the exercise log had a higher correlation than duration and intensity of walking, with change in VO2 max suggesting that frequency was potentially the most predictive adherence measure. Examination of the total number of walks and the number and sequence of weeks without walks over the 24-week intervention revealed dynamic patterns of adherence suggesting variation in the degree of behavioral change. PMID- 11216028 TI - Spiritual perception, attitudes about spiritual care, and spiritual care practices among nurse practitioners. AB - The purpose of the nonexperimental study was to examine the relationships among spiritual perception, attitudes about spiritual care, and spiritual care practices in nurse practitioners. Attitudes about providing spiritual care and spiritual care practices have been studied among nurse generalists, but little research has been conducted on nurses in advanced practice. All nurse practitioners registered by the state of Indiana were sent Reed's Spiritual Perspective Scale (SPS) and a modified version of the Nurses' Spiritual Care Perspectives Scale developed by Taylor, Highfield, and Amenta. Pearson correlation techniques were used to test for significant relationships. Statistically positive relationships were between perception of personal spirituality and 9 of the 12 spiritual care practices. Eight of the 13 items describing attitude toward providing spiritual care were statistically significant with the SPS. Implications of the findings are discussed. PMID- 11216029 TI - Vascular skin ulcers. Handle with care. PMID- 11216030 TI - Health tips. Constipation while traveling. PMID- 11216031 TI - New cholesterol-lowering drug is now available. PMID- 11216032 TI - Colon cancer screening may change with DNA test. PMID- 11216033 TI - Sudden cardiac death. Fast action is needed. PMID- 11216034 TI - Laparoscopic hernia repair. A faster, easier way. PMID- 11216035 TI - Chocolate. Your heart's delight? PMID- 11216036 TI - A friend sent me a copy of the Mayo Clinic Diet. It seems to advocate a lot of grapefruit and high protein foods. Is this the "real" Mayo Clinic Diet? PMID- 11216037 TI - I've heard of an herbal alternative to Viagra for impotence. Does it work and is it safe? PMID- 11216038 TI - Staying ahead of the game. PMID- 11216039 TI - A review of Congressional action 2000. PMID- 11216040 TI - Measuring HIPAA's impact. PMID- 11216041 TI - Communication, collaboration, and compliance. PMID- 11216042 TI - Is PKI (public key infrastructure) the solution to HIPAA security? PMID- 11216043 TI - The journey of 1,000 miles: are providers really ready for HIPAA's privacy requirements? PMID- 11216044 TI - Final privacy rule puts health information in national spotlight. PMID- 11216045 TI - The new privacy officer's game plan. AB - The HIPAA-mandated privacy officer role offers a new opportunity for HIM professionals. What skills are required, and what needs to be done first? This article answers these questions. PMID- 11216046 TI - Wrestling the HIPAA security regulations: two experts' advice. Interview by Steven Austin. PMID- 11216047 TI - HIPAA compliance questions for business partner agreements. AB - If your organization is covered by HIPAA, do you know what's expected of you--and of your vendors--with regard to privacy of health information? To make sure your organization is in compliance, contracts with business partners will need careful review. The author offers an overview of the proposed regulations and offers some tips to get started. PMID- 11216048 TI - 10 HIPAA tips for the physician office. PMID- 11216049 TI - New APCs (ambulatory patient classifications) for a new year: more OPPS changes. PMID- 11216050 TI - Remote coding at home: tips for success. PMID- 11216051 TI - Improving performance, managing change. PMID- 11216052 TI - Electronic signatures at work. PMID- 11216053 TI - Practice brief. Verbal/telephone order authentication and time frames. American Health Information Management Association. PMID- 11216054 TI - Helping star performers shine. PMID- 11216055 TI - Another look at home care PPS. PMID- 11216056 TI - Preparing the physician office for HIPAA. PMID- 11216057 TI - Opening a window to a hospital's soul. PMID- 11216058 TI - Is managed care going small? PMID- 11216059 TI - Medical cost offset: do the numbers add up? Yes. PMID- 11216060 TI - Medical cost offset: do the numbers add up? No. PMID- 11216061 TI - Credo for a care manager. Use of clinical principles can improve relations with providers. PMID- 11216063 TI - Using the Internet to really connect. PMID- 11216062 TI - Is generic really the same? PMID- 11216064 TI - Information on the Internet: consumers take the lead. PMID- 11216065 TI - Universal connectivity. The Internet race is on. PMID- 11216066 TI - Congress restores Medicare funding. PMID- 11216067 TI - OSHA's ergonomic standard in the health care workplace. PMID- 11216068 TI - Surviving the survey. Is process hurtful or helpful? PMID- 11216069 TI - Caregiving. Keep aging minds alert. PMID- 11216070 TI - Is liability coverage an endangered species? PMID- 11216071 TI - Unmasking fraud and abuse. The pursuit is on via internal compliance programs. PMID- 11216072 TI - Basic marketing 121. Long term care marketing is as easy as one-to-one. PMID- 11216073 TI - The income statement. The "financial engine" for assisted living. PMID- 11216074 TI - A 'long-term' administrator. Interview by Suzanne Bilyeu. PMID- 11216075 TI - [Use of digitalis in chronic heart failure: an unresolved problem?]. AB - The role of digitalis in the treatment of patients with heart failure is still being debated. The DIG study, a trial which enrolled about 6800 patients with the aim at overcoming the doubts on efficiency and safety of digoxin, showed a neutral effect on mortality but there was a statistically significant decreased risk of hospitalization due to worsening heart failure in the digoxin group compared to the placebo group. The trial disclosed several problems about patient selection (many patients were on digitalis before the start of the trial), digoxin dosage, which seemed to be high, and about the true reported beneficial effects of this therapy. Finally the data available do not permit any evaluation on the use of beta-blockers and the association between digitalis and beta blockers considering the properties of these drugs in suppressing orthosympathetic activation. PMID- 11216076 TI - [Controversies regarding distribution, instrumentation, and competence of hemodynamics laboratories]. AB - In the last few years we have witnessed a substantial growth in the number of catheterization laboratories, especially in the northern regions of Italy, a phenomenon which has met some controversy and has been discussed in a Symposium at the ANMCO National Conference (Florence, May 20-23, 2000). The controversy is essentially between those who believe in the implementation of catheterization laboratories in all cardiology units equipped with a cardiological intensive care unit (and the creation of a functional network with the tutorial centers) and those who refer to the existing guidelines, standards and VRQ which envisage a geographical distribution of laboratories on the basis of a balance between needs of the population and the minimum quantity of procedures performed by each center in order to guarantee the best quality and cost-effectiveness. The aim of the Symposium was to clarify whether the two "innovations" of these last few years, namely the introduction of new portable radiological equipment on the one hand and the effectiveness of primary angioplasty in the treatment of acute myocardial infarction on the other, may influence the redefinition of criteria regarding the distribution of laboratories, taking into account as well the expansion of indications for coronary angioplasty and coronary angiography. After a lively discussion, the proceedings can be summed up as follows: no agreement was reached regarding the role of portable radiological equipment in the decisional process regarding the setting up of a new catheterization laboratory; primary angioplasty should be carried out in centers with an adequate volume of activity and a functioning inter-hospital organizational structure for this demanding activity; otherwise it does not offer any advantages over fibrinolytic therapy; the proposal of a new organizational model is based on the creation of transverse inter-hospital cardiology departments, the size of which is based on the overall size of the user population, with interventional laboratories distributed in the reference hospitals and diagnostic laboratories in hospitals equipped with a cardiologic intensive care unit (where there is a sufficiently large user population to guarantee at least the minimum number of procedures envisaged by the standards); both parts should work in close cooperation. On this last point there was a contrasting opinion and it was not possible to reach a consensus. The Scientific Societies should formally express their views on this controversial topic, so that guidelines, standards and VRQ can be updated rapidly. The latter should constitute the reference for the procedures of accreditation to which all laboratories and cardiology departments are subjected to, and it is likely that this will be the best way to overcome the present controversy. PMID- 11216077 TI - [Need and quality assurance: can the introduction of the new generation mobile systems change the reference standards?]. AB - The new generation of radiological mobile systems, by lowering the installation and depreciation expenses, has led to start new low volume catheterization laboratories. These equipments allow to obtain good quality images, but they are not so reliable for extended performances, so that they are not suitable for interventional procedures. On the other hand, the extension of the indications to coronary angiography and angioplasty, with the related increase in the population needs, leads the resetting of the reference areas to start new catheterization laboratories. Anyhow lowering of expenses and of the extension of the reference areas does not change the need for maintaining high activity levels of centers and first operators in order to guarantee the quality of diagnostic and interventional procedures. The optimal levels of centers in national standards are 800 coronary angiographies and 400 coronary angioplasties per year: these numbers indicate the experience necessary to warrant the quality of procedures, with optimal results and low rate of complications, therefore they should not be changed. The spreading of laboratories due to the new low cost radiological equipments leads to an increase in inappropriate procedures and in the total expenses for the management of cardiac patients, without a proportional advantage in prognosis and quality of life. In order to ensure a quick diagnostic and therapeutic process to all the patients who need invasive procedures, instead of starting new centers, it is worthwhile to perfect the efficiency of links among small and main centers following shared pathways. PMID- 11216078 TI - [Can primary angioplasty result in the increase of the number of hemodynamics laboratories?]. AB - Randomized studies comparing primary angioplasty with fibrinolysis have shown that mechanical intervention is superior to fibrinolytic treatment in terms of effective reperfusion, resulting in a decreased mortality rate and a lower incidence of reinfarction and recurrent ischemia. However, the effectiveness of a primary angioplasty strategy is strongly dependent on logistic models. Survey studies, and the GUSTO IIb trial have shown no clinical benefits of primary angioplasty over pharmacologic treatment in the "real world". Thus, a primary angioplasty program should be considered only if high performance technical and logistic models can be applied. These include surgical back-up, high volume cath lab, and an effective network of patient transportation, and as a consequence, the most cost/effective model may be identified in a tertiary referral center, and in the regionalization of the myocardial infarction centers. PMID- 11216079 TI - [Hemodynamics studies with the new generation portable systems: cost-benefit analysis]. AB - Coronary angiography facilities are usually available only in major medical centers despite an increasing utilization in managing patients with ischemic heart disease. In recent years portable fluoroscopic imaging systems have been developed to reduce costs and bring coronary angiography services closer to patients. Our experience with the OEC Medical System 9600 demonstrates that the portable systems of new generation are reliable both regarding the quality of coronary angiograms and the routine use in a multipurpose cardiac catheterization laboratory. This statement is based on our 1-year experience (1999) with a caseload of 740 studies or procedures: 342 coronary angiographic studies, 159 electrophysiological studies, 74 radiofrequency catheter ablations, 126 pacemaker implantations/replacements, 16 cardioverter-defibrillator implantations/replacements, and 23 other studies or procedures. The mean cost of a coronary angiography was Itl 512,000 (265 Euro) in the in-house laboratory; it would have been Itl 694,000 (359 Euro) in the historical scenario, i.e. with referral to a 25 km distant laboratory, with Itl 182,000 (94 Euro) saved. Our experience is consistent with the accepted criteria of good laboratory performance and cost-effectiveness. PMID- 11216080 TI - [A new organization model for hemodynamic cardiology diagnosis and intervention cardiology]. AB - In centers without hemodynamic laboratories the quality of medical care may be suboptimal since the unavailability of these technologies may reduce medical experience in the treatment of heart disease, mostly in acute coronary syndromes, and may increase the need for referring some patients to other hospitals. The problem will be of great relevance in the case of expansion of the aggressive approach in the treatment of acute ischemic syndromes such as acute myocardial infarction and unstable angina. The impelling need for small centers of improving medical care may promote the spontaneous and uncontrolled proliferation of hemodynamic laboratories. The high number of hemodynamic laboratories may lead to a low institutional volume and, as a consequence, may negatively influence the outcome of coronary intervention and increase health care costs. The experience of operators and the costs are probably more relevant as regards angioplasty than coronary angiography. Therefore we propose the implementation of departments of interventional hemodynamic laboratories including different hospitals: diagnostic laboratories will be allocated in hospitals with coronary care units, while interventional laboratories will be allocated in referring hospitals. PMID- 11216081 TI - [Effectiveness and adequacy of management of acute coronary syndromes]. AB - A rational utilization of resources represents a key issue in modern treatment of cardiac patients. The aim of our study was to highlight a few essential aspects for an efficient and appropriate management of patients with an acute coronary syndrome. Clinical evaluation of the patient's risk (i.e. clinical assessment of the probability of developing a cardiac event), incremental value of the chosen test for risk stratification, value of a strategy in modifying outcome and direct determinants of medical cost of the strategy are selected as the main aspects to be considered in order to optimize management of these patients. PMID- 11216082 TI - [The new limitations of the Italian Regulatory Agency on Drugs]. AB - In Italy the reimbursement of few free-of-charge drugs is limited to subgroups of patients or to one of the approved indications. In February 2001 new rules will become mandatory for Italian physicians. The text of the new rules related to drugs mostly used by cardiologists (levocarnitine, ticlopidine, hypolipemic drugs) is reported. PMID- 11216083 TI - [Effectiveness and side effects of the treatment with propafenone and flecainide for recent-onset atrial fibrillation]. AB - BACKGROUND: The authors report their experience in recent-onset atrial fibrillation treated with intravenous flecainide and propafenone, in comparison with the placebo group. METHODS: We randomized 352 (138 in the flecainide group, 164 in the propafenone group and 50 in the control group) consecutive patients (167 males, 185 females, mean age 59 +/- 12 years) with recent-onset atrial fibrillation. The electrocardiogram of all patients was monitored for at least 24 hours. RESULTS: The restoration of sinus rhythm occurred in 72.5, 80.4, 86.2 and 89.8% of patients in the flecainide group; in 54.3, 68.3, 75 and 92.1% in the propafenone group; in 22.2, 27.8, 35.2 and 46.3% in the control group, at 1, 3, 6 and 24 hours respectively. The occurrence of side effects was the same in all treatment groups, and occurred in about 10% of patients in the flecainide and propafenone groups, and in 4% in the control group. In our study population the treatment of recent-onset atrial fibrillation with flecainide was faster in converting the arrhythmia to sinus rhythm (p < 0.005 at 1 hour, p < 0.05 at 3 hours, p = 0.05 at 6 hours). However within 24 hours the efficacy of either flecainide or propafenone was the same (p = NS at 24 hours). CONCLUSIONS: Side effects were similar in both treatment groups. In particular malignant arrhythmias did not occur in the treatment groups and in the control group. PMID- 11216084 TI - [Criteria for work capacity evaluation, adequacy for specific jobs, attitudes towards physical activity and sports, and insurance eligibility in subjects with congenital cardiopathy]. PMID- 11216086 TI - [Physical activity and mortality in older men with diagnosed coronary heart disease]. PMID- 11216085 TI - [New anti-platelet strategies]. AB - In the 1960s, the platelet inhibitory properties of several drugs were discovered. Like aspirin, they were already in clinical use for other therapeutic indications. Since then, the search for new and more rational antiplatelet strategies has been constant but only moderately successful, although new molecules with high selectivity for platelet function have been developed. The authors briefly review some recent advances in platelet pharmacology and focus their attention on pharmacogenetics, a potential approach to new antiplatelet strategies. Would this approach be successful, individuals rather than epidemiologically defined groups of patients might better benefit from newly targeted antiplatelet drugs. PMID- 11216087 TI - [Plasma homocysteine predicts mortality independently of traditional risk factors and C-reactive protein in patients with angiographically defined coronary artery disease]. PMID- 11216088 TI - [Comparison of vasopeptidase inhibitor, omapatrilat, and lisinopril on exercise tolerance and morbidity in patients with heart failure]. PMID- 11216089 TI - [Effect of amlodipine on the progression of atherosclerosis and the occurrence of clinical events]. PMID- 11216090 TI - [Multiple complex coronary plaques in patients with acute myocardial infarction]. PMID- 11216091 TI - [Risk stratification]. PMID- 11216092 TI - [Evidence-based and everyday medicine: a problem not only Italian]. PMID- 11216094 TI - [Drug administration in tube-fed patients ]. PMID- 11216093 TI - [Evidence-based medicine: several clarifications]. PMID- 11216095 TI - [Metabolic response to stress, can we control it?]. AB - When faced by an external aggression such as shock, sepsis, burns or surgery, the body develops a response, known as stress, comprising hypermetabolism and hypercatabolism related to an alteration in tissue sensitivity to insulin. This alteration seems to be rooted in the transmembrane protein GLUT-4 which takes care of the cell uptake of glucose in skeletal muscle. As a result, there are alterations in the metabolism of carbohydrates, fats and proteins (reduction of immunoglobulins). In the case of surgery, it has been shown that, on the one hand, factors such as rest, pre-operative fasting or the release of inflammatory response factors constrain an even greater alteration in the sensitivity to insulin; and on the other hand that the degree of resistance to insulin depends on the magnitude of the surgery, its duration, bleeding, or on hypothermia and extracorporeal circulation in the case of heart surgery. These metabolic alterations may lead to an increase in the number of infections, mean stay in hospital, and even lead to diabetes mellitus in the long term. Over the last few years, all of this has led several researchers to try to minimize the stress response associated with planned surgery through replacing pre-operative fasting by the administration of carbohydrates, whether or not in association with insulin in perfusion. Beneficial results have been described: control of hyperglycaemia, lower consumption of neoglycogenic amino acids and less alteration of plasma immunity (interleukins, TNF). Future studies will evaluate the influence of these measures on plasma immunity, mean hospital stay and morbidity/mortality. PMID- 11216096 TI - [Feeding and nutrition in Alzheimer's disease]. AB - Dementia is an organic brain disease. The most frequent type of dementia is Alzheimer's and it affects mostly elderly people. Due to the increase in life expectancy and to the ageing of the population, Alzheimer's has recently become an area of research of interest. The eating behaviour and nutrition of elderly people has some special characteristics which become particularly relevant during illness. An Alzheimer's patient suffers a progressive decay in their functional and physical abilities, and these renders them at high nutritional risk. Prevention, rapid intervention and ensuring an adequate nutritional intake is essential in each of the dementia stages. This paper reviews the most important nutrients influencing the development or worsening of dementia and the guidelines for food intake throughout the disease. PMID- 11216097 TI - [Follow-up of drug administration through nasogastric tube: development of a practice guideline]. AB - GOAL: To carry out a study of how medication is administered by catheter in daily practice in our hospital. To prepare a practical guide for the administration of medication by catheter. SCOPE: STUDY POPULATION: in-patients using enteral feeding tubes, except ICU. Study duration: 2 months. INTERVENTIONS: Through a single-dose medication distribution system, the nutrition team's pharmacist prospectively collects the data on the medication of patients subjected to enteral feeding through a catheter and compares these data with the nursing record and, if the medication has been incorrectly handled, makes the pertinent recommendations. Using the information obtained from the pharmaceutical industry and a review of the literature, a guide is drawn up for the medicines used with catheters. RESULTS: The study was carried out with 25 patients receiving enteral nutrition. A total of 55 different pharmaceutical preparations were used. Administration was correct in 116 of the 123 medicines prescribed (91%); the other 5 drugs (9%) were incorrectly handled. A total of 16 alterations were recommended in 25 patients (64 recommendations/100 patients), of which 9 involved a change of pharmaceutical form from solid to liquid, 4 were due to incorrect handling of the solid form, 2 because of interaction between the medication and enteral nutrition and 1 because of interaction between concomitant medications. A guide was drawn up for the administration of medication by catheter, covering a total of 179 active substances and 197 pharmaceutical products. CONCLUSIONS: The presence of a pharmacist in clinical units facilitates the detection and solution of problems associated with the administration of medication via catheters. The preparation of a handbook as a tool for the intra-catheter administration of medicines is a useful starting point for improving the use of medication and facilitating nursing tasks. PMID- 11216098 TI - [Nutritional status of the HIV patient. Description and clinical course of a group of patients over a year]. AB - GOAL: To know the nutritional and immunological status of a sample of patients infected by HIV and their evolution over a one-year period. Relationship between nutritional status, immunological status and clinical evolution. METHOD: Longitudinal descriptive study of 30 HIV-infected patients. Anthropometric evaluation (weight, height, skin folds, arm circumference) and immunological assessment (CD4 and CD4/CD8). STATISTICAL ANALYSIS: means, absolute and relative frequencies, Student's T test. RESULTS: 30 patients, 73.3% males and 27.7% female. Mean age 34.7 years. Initial nutritional assessment: 30% of patients had normal weight, 36.7% presented mild undernourishment, 16.7% moderate undernourishment, 6.7% were overweight and 10% were obese. The evolution of CD4 and CD4/CD8 levels was not significantly influenced by nutritional status. CONCLUSIONS: The patients in the study presented a deterioration of their nutritional status, as assessed by triceps skin fold. The nutritional status of the HIV-infected patients in our study is not dependent on their immunological status. The diagnosis and treatment of their de-nourishment on diagnosis of HIV infection will contribute to the prevention of complications, thus reducing the human and health-care costs. An increase in food intake, on its own, does not improve the condition of the patients, indicating the need to provide them with the necessary dietary supplements from the early stages of illness. PMID- 11216099 TI - [Reversible hypertransaminasemia after diet therapy]. AB - An increase in transaminases may be due to multiple causes. We present a case of reversible hypertransaminasemia following specific dietary therapy. The various potential aetiopathogenies are reviewed to explain the raising of transaminase levels and the improvement in analytical results after the institution of this dietary treatment. PMID- 11216100 TI - Pharmacy immunization partnerships: a rural model. AB - OBJECTIVES: To describe the Pharmacy Immunization Project, a pharmacy/county health department (CHD) partnership model for immunizing infants and adults in rural areas, and to develop service procedures and disseminate lessons learned for adapting the model to different settings. SETTING: Independent community pharmacies in five contiguous rural counties in West Virginia. PRACTICE DESCRIPTION: Participating pharmacies varied markedly in space, prescription volume, and population of service areas. PRACTICE INNOVATION: Childhood and adult immunization service. INTERVENTIONS: Pharmacists partnered with nurses from CHDs to offer year-round immunizations at times when other providers were typically closed. Working under standing orders of the CHD medical directors, nurses also conducted routine well-baby examinations in the pharmacy. Promotions involved direct mailing, posters, fliers, direct communication, and ads in newspapers, radio, and TV. MAIN OUTCOME MEASURES: Pharmacists' and CHDs' continued willingness to participate, use of the service by local citizens, and feedback from participants and other health care providers and the West Virginia Immunization Program (WVIP). RESULTS: All sites except one continued their participation through the life of the project. The one exception was a pharmacy with few infant patients, which discontinued participation during year 4 of the project. Remaining sites were used and well accepted by the community. The WVIP remains a loyal supporter, and no problems arose with local health care providers. CONCLUSION: The model appears adaptable to urban as well as rural practice and to chain as well as independent practice in states not authorizing pharmacists to administer vaccines, for pharmacists who for other reasons prefer not to administer, and for those who prefer to offer adult immunization on a seasonal basis. From the CHD perspective, the partnership model is useful in establishing "satellite" locations to target hard-to-reach patients. Recommendations regarding agreements and responsibilities are available, as are lessons learned during project development. PMID- 11216101 TI - Regulating for outcomes as a systems response to the problem of drug-related morbidity. AB - OBJECTIVE: To describe the evidence that preventable adverse outcomes of drug therapy are prevalent in the United States and Europe, to describe the causes of this problem, to outline a systems response that would correct or improve the problem, to discuss pharmacy's contribution to that solution, and to propose a strategy for implementation. SUMMARY: The causes of the widespread problem of preventable drug-related morbidity (PDRM) that have been identified in the literature constitute system failure. Health professionals can understand an individual patient's care system if they organize their thinking about systems as efficiently as they organize their thinking about medical or pharmaceutical problems. Six essential system characteristics are proposed, based on the PDRM literature. Regulations should mandate regular patient and system performance assessments--specifically, that health professionals (1) identify, resolve, and document specific pharmacotherapy problems; (2) assess system performance and identify recurring root causes of problems; and (3) document assessments, problems found, actions taken, and follow-up. These regulations would, in essence, mandate individual quality improvement (QI) programs. QI and pharmaceutical care require similar processes of decisions and actions, one from a practice (multipatient) perspective and the other from a patient perspective. CONCLUSION: Health care accreditation agencies are moving toward regulation for outcomes. Pharmacy managers should embrace and regulatory boards should participate in this movement. Such regulations would clarify pharmacy's role in support of safe and effective pharmacotherapy and would constitute a commitment to pharmaceutical care as public service. A widely adopted system of measuring and improving the quality of medication use and outcomes could eventually lead to quality benchmarks in the community pharmacy setting, which would more firmly establish the value of the pharmacist in pharmacotherapy. PMID- 11216102 TI - Credentialing in pharmacy. PMID- 11216104 TI - Collaborative practice agreements--further evidence of acceptance and success. PMID- 11216103 TI - Pharmacy-based immunizations--an idea whose time has come. PMID- 11216105 TI - From professional advocacy to patient advocacy: a gambit for pharmacists. PMID- 11216106 TI - Pharmaceutical care: how pharmacy could benefit from regulatory action. PMID- 11216107 TI - The American Practice of Pharmacy, 1902-1952. PMID- 11216108 TI - APhA drug treatment protocols: comprehensive weight management in adults. PMID- 11216109 TI - Pharmacists and immunizations: a national survey. AB - OBJECTIVES: To obtain information about pharmacists' current involvement in and willingness to provide immunization services, and to assess perceived barriers to providing immunization services. DESIGN: Cross-sectional mail survey. SETTING: National. PATIENTS OR OTHER PARTICIPANTS: Random sample of 5,342 pharmacists from chain, independent, mass merchandiser/grocery, primary care clinic, and health maintenance organization settings. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Responses to survey on pharmacy-based immunization services--current involvement, willingness to get involved, perceived obstacles, and patients' interest. RESULTS: Three mailings yielded a response rate of 25.3% (1,348 responses). Only 53.1% of respondents knew correctly whether their state allowed pharmacists to administer immunizations. Although a significant number of pharmacists were involved in immunization activities, such as counseling and promotion, only 2.2% and 0.9% of respondents were involved in actual administration of adult and childhood immunizations, respectively. In general, men, independents, owners/partners, and pharmacists who had attended immunization-related educational programs were more willing to provide immunization services than were women, chain and staff pharmacists, and educational program nonattendees. Pharmacists who had attended immunization-related educational programs also perceived pharmacist- and patient-related factors as less problematic for pharmacy-based immunization services than did nonattendees. CONCLUSION: This survey provides a baseline measure of the nature and extent of pharmacist involvement in immunizations that can be used now and in future years. The profession can use the findings on pharmacists' willingness to provide immunization services and their perception of obstacles to such services as a basis for targeted educational and promotional programs and materials. PMID- 11216110 TI - Payment for pharmaceutical care? PMID- 11216111 TI - People vaccinated by pharmacists: descriptive epidemiology. AB - OBJECTIVE: To describe the demographic, clinical, and attitudinal characteristics of people vaccinated by pharmacists, using a multistate sample of pharmacists and a more extensive set of parameters than previous studies. DESIGN: Cross-sectional survey. PATIENTS AND OTHER PARTICIPANTS: 1,730 adults vaccinated at 21 community pharmacies in 17 cities in 10 states. MAIN OUTCOME MEASURES: Vaccinees' age, sex, and selected demographic characteristics; current medications and prescription use patterns; distance traveled to pharmacy; and opinions about vaccine providers. RESULTS: 60% of respondents were women; average age was 54 +/- 15 years. One-quarter were age 65 years or older. About 9% were younger than 65 and took medication for chronic heart or lung disease or diabetes. Almost half took prescribed medications chronically, and 84% came to the pharmacy intending to be vaccinated. All of the respondents believed they were treated respectfully. Many respondents considered the pharmacy advantageous, compared with other vaccine providers, based on access, proximity, trust, convenience, and/or cost. CONCLUSION: Respondents vaccinated by a community pharmacist were satisfied with the experience and would recommend it to others. PMID- 11216112 TI - Role of CYP3A4 and P-glycoprotein in drug interactions involving the HMG-CoA reductase inhibitors. PMID- 11216113 TI - Patients' acceptance of traditional and nontraditional immunization providers. AB - OBJECTIVE: To examine patients' acceptance and reported use of traditional and nontraditional immunization providers and settings. DESIGN: Survey. SETTING: Stratified sample of private family physician clinics, family medicine residency training programs, community pharmacies that provide immunizations under standing order protocols, and nonimmunizing community pharmacies, all located in Iowa. PATIENTS OR OTHER PARTICIPANTS: Individuals presenting for medical care or pharmacy services. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Sources of past immunizations, 'access to immunizations, importance of immunization records, and future use of different health care providers and settings for immunizations. Univariate and multivariate analyses were performed to examine the relationships between patient demographics and recruitment site on the question responses. RESULTS: 420 surveys were returned (67% response rate). Respondents frequently received immunizations at sites other than physician offices. Younger patients and those living in smaller towns were more likely to report receiving an immunization from a nonphysician. Patients recruited in immunizing pharmacies more often reported previous immunization by a pharmacist (P < .001), most often for influenza. Respondents often reported that it was more convenient to receive an immunization outside a physician office. Greater support was noted for receiving adult immunizations from nonphysicians and in nontraditional settings, whereas traditional settings and providers (physician offices, community health departments) were preferred for childhood immunizations. CONCLUSION: Iowans report accessing different health care providers and settings for their routine immunizations. In general, they are more likely to support using traditional immunization providers and settings for childhood immunizations but are less exclusive about where they receive adult immunizations. Pharmacists should consider focusing initial efforts on administering adult immunizations, due to greater patient acceptance of nontraditional immunizers for adult immunizations. PMID- 11216114 TI - Children and smoking. PMID- 11216115 TI - The emergency contraception collaborative prescribing experience in Washington State. AB - OBJECTIVE: To describe how prescribers and pharmacists view the Emergency Contraceptive Pills (ECP) program, and to evaluate pharmacists' performance through the use of a consumer survey. DESIGN: Self-administered provider satisfaction surveys were mailed 6 months after the program's inception. Consumer satisfaction surveys were distributed at the point of ECP service for return by mail. SETTING: The program encouraged pharmacists and prescribers in western Washington to enter into collaborative prescribing agreements, increasing consumers' access to ECP. PATIENTS OR OTHER PARTICIPANTS: Pharmacists who had attended ECP training sessions, prescribers who had authorized pharmacists to prescribe ECP, and women who had been prescribed ECP by pharmacists. MAIN OUTCOME MEASURES: Providers' reasons for participating, attitudes toward the ECP program, and experiences with ECP as a result of the program; feedback from women receiving ECP from pharmacists. RESULTS: 309 pharmacist surveys and 55 prescriber surveys were sent, of which 159 (51%) and 27 (49%), respectively, were returned. Meeting patient needs and having a professional responsibility to participate were commonly reported reasons for ECP program involvement. Both pharmacists and prescribers (92%) reported being "satisfied" or "very satisfied" with their prescribing agreements. On the 470 consumer surveys returned out of 7,000 distributed (6.5%), pharmacists were rated highly satisfactory for their interactions with patients and the quality of information about ECP use given, but less satisfactory for information about adverse effects, recognition and follow-up of ECP failure, and regular contraceptive methods. CONCLUSION: All participants expressed satisfaction with the ECP program. This example should support the initiation of similar programs in other states. PMID- 11216116 TI - Medication management in primary and secondary schools. AB - OBJECTIVE: To summarize present knowledge about medication management in primary and secondary schools; to place this knowledge in its drug use and organizational contexts; and to provide a foundation for studying the problem and developing policy- and practice-level interventions aimed at alleviating it. To offer recommendations for practitioners, policy makers, and health professions educators aimed at improving the situation. DATA SOURCES: MEDLINE database (1966 1998); International Pharmaceutical Abstracts database (1977-1998); complete Medscape full-text search; contents of the Journal of School Nursing and the Journal of School Health (1966-present). STUDY SELECTION: We reviewed 95% of all articles, books, and reports identified using the search terms elementary school, middle school, junior high school, high school, primary school, secondary school, school nurse, school health, and schoolchildren. DATA EXTRACTION: The literature on this topic includes background material describing the nature of the problem and its political and organizational context and implying its significance; summaries of regulations, guidelines, and recommendations regarding medication management in the schools; and empirical studies. Few articles address pharmacist involvement in medication management in schools. DATA SYNTHESIS: Although approaches to this important problem vary widely, a set of core medication management guidelines is identifiable. Formal research is sparse, but it shows that medication use is widespread in schools and carries significant therapeutic and safety consequences. CONCLUSION: Pharmacists and school nurses must cross professional borders if they wish to play a role in solving this important drug therapy problem. Pharmacists can provide therapeutic and contextual perspectives on the problem, while school nurses can implement solutions within the schools. PMID- 11216117 TI - Drug abuse and dependency: understanding gender differences in etiology and management. AB - OBJECTIVE: To review the etiology, consequences, and treatment needs of drug abuse and dependency, especially in women. DATA SOURCES: Original studies and literature reviews published primarily since 1990. DATA SYNTHESIS: Many studies, conducted mostly during the past 10 years, are providing new information regarding the genesis of two separate drug problems: willful abuse (misuse) of drugs and pathological drug dependency. Recent studies have also highlighted important differences between the sexes in the causes, consequences, and management of drug abuse and dependency. The neurobiologic and genetic contributions to the pathological disease of addiction provide important directions for future treatments, as a supplement to existing self-help and structured behavioral therapies. Pharmacotherapy also has an important role in reducing drug craving and relapse in addicted patients. CONCLUSION: Although the precise causes of drug abuse and dependency continue to challenge researchers, important differences have been identified between men and women in terms of how drug use begins, how it progresses, and effective methods of treatment. Pharmacists and other health care professionals need to understand gender differences in the etiology and management of drug abuse and dependency and develop the capacity to recognize and refer women who may be abusing or dependent on drugs. PMID- 11216119 TI - Dueling forces: I-Med vs. Fed-Med. PMID- 11216118 TI - A tool for corporate decision making about cognitive pharmaceutical services. AB - OBJECTIVE: To present and discuss the models, theories, ideas, and frameworks that corporate decision makers would apply to the implementation of cognitive pharmaceutical services. BACKGROUND: Large chains and integrated delivery networks dominate the pharmacy marketplace. As a result, in many instances implementing cognitive pharmaceutical services, or expanding their delivery, first requires approval of a corporate decision maker, often not a pharmacist, who is schooled in marketing, management, and finance, and who necessarily views proposals for cognitive pharmaceutical services from those frames of reference. This article focuses on the following six marketing and management questions that corporate decision makers likely want answered before approving and funding the implementation of cognitive pharmaceutical services: (1) What is our product? (2) Who will pay, and what is the price? (3) Is there a market, and can it be reached? (4) What procedures must be put in place? (5) Who will deliver the service? (6) Where are the services to be delivered, and how is the facility to be presented? DISCUSSION: For a pharmacy manager charged with bringing cognitive pharmaceutical services to the marketplace, consideration of the issues detailed here meets a reasonable test of due diligence in committing human, financial, and organizational resources. CONCLUSION: It is natural for a pharmacist to look at cognitive pharmaceutical services through a professional lens. It is just as natural for a corporate decision marker to look at cognitive pharmaceutical services through a marketing and management lens. Unless both lenses are put together, one gets only half the picture. PMID- 11216120 TI - CEO performance appraisal: review and recommendations. AB - CEO performance appraisal (PA) is very valuable to an organization, but the chances of obtaining a PA of high quality decrease as executive responsibility increases. The realities of CEO PA are that it: (1) is inevitable; (2) is creative and complex; (3) involves politics; and (4) has a significant effect on the organization and the executive. PA is conducted for legal and social requirements, to enhance communication, to provide opportunities for improvement, and to relate performance to compensation. This article discusses several problems with chief executive officer (CEO) PA and the contemporary approaches that seek to improve it. Three fundamental areas for evaluation are identified: (1) organizational success; (2) areawide health status; and (3) professional role fulfillment. These provide an outline for successful healthcare PA. In addition to a discussion of the strategic considerations behind a successful CEO PA system, several recommendations are offered for the implementation of the annual evaluation process. The final goal of CEO PA is to link its results to CEO incentive compensation. It is strongly recommended that some portion of the CEO's salary directly hinge on his performance in two critical areas: organizational effectiveness and community health status. PMID- 11216121 TI - Interview with John R. Griffith, FACHE, author of the Well-Managed Healthcare Organization. Interview by Kyle L. Grazier. PMID- 11216122 TI - Spirituality and healthcare organizations. AB - In recent years, the place of spirituality in organizations has become increasingly discussed and advocated. On a personal level, this may involve achieving personal fulfillment or spiritual growth in the workplace. In the broader sense, spirituality is considered by many to be essential in an organization's interactions with employees, customers, and the community. This article describes a possible role for greater spirituality in healthcare organizations, whose cultures in recent decades have largely excluded spirituality or religiousness. This is the consequence of an analytical, scientific perspective on human health; a reductionist paradigm in biomedical research; and the inevitable bureaucratization occurring in large healthcare organizations. However, in recent decades, numerous scientific articles supporting a connection between faith or religiousness and positive health outcomes have been published. Because individuals seek meaning when experiencing severe illnesses, and humans universally respond to compassion and caring, spirituality among healthcare workers and managers appears highly appropriate. The article describes organizational barriers to the greater inclusion of spirituality in healthcare and presents several approaches to developing a more caring organization. These include eliciting extensive input from all staff and clinicians in identifying core or common values, ethics, and a philosophy of caring. Programs should ensure that the views of nonreligious staff and patients are respected and that clear guidelines are established for the extent and nature of affective or spiritual support for patients. PMID- 11216123 TI - Better information for the board. AB - Healthcare managers are making quicker, riskier decisions in an increasingly competitive and regulated environment. Questions have been raised regarding the accountability and performance of boards of these organizations, as board members are not always selected based on their competencies to guide such decisions. Adapting mission and strategy and monitoring organizational performance require information that boards get mostly from management. The purpose of this study was to examine the information that boards regularly get to carry out their functions. I obtained board documents from four not-for-profit hospitals and health systems in different boroughs of New York City. At each institution, I conducted one-hour interviews with at least three board members and three top managers. I also attended at least one board or executive committee meeting and one additional meeting, usually of the finance committee. Principal findings were that the boards get too much data, the same data that management gets, and little comparative data on performance of similar benchmarked organizations. Board members and managers are satisfied with the information that board members get and have no plans to improve their system of shaping, or the quality of, information. Key recommendations to boards and managers are: (1) boards must take greater responsibility for identifying the information that they get and how they wish to get it, (2) managers must ensure that measurable objectives are developed, against which organizational performance can be evaluated, (3) boards must get information that is targeted and shaped to better fit board functions, (4) managers must develop information sets for main service lines, (5) boards must get information on the expectations and satisfaction levels of key stakeholders, (6) boards must get better and more focused information on performance of benchmarked institutions, and (7) boards must get less hospital operating data on a monthly basis. PMID- 11216124 TI - Developing an air ambulance service for a remote area of west Texas. PMID- 11216125 TI - Career performance: how are we doing? PMID- 11216127 TI - Self-functioning traits affecting meal compliance in eating disorder patients. AB - The objective of this study was to measure the extent to which self-functioning traits relate to meal compliance in eating disorder patients by using multiple regression analysis. Compliance was the dependent variable. It was recorded on a meal flowsheet during breakfast, lunch and dinner and compiled for the 8 days immediately preceding each patient's discharge. The independent variables were gender, self-esteem (Rosenberg Scale) and 7 subscales of the Eating Disorder Inventory (EDI-2): drive for thinness, body dissatisfaction, ineffectiveness, perfectionism, interpersonal distrust, interoceptive awareness and maturity fears. A random sample of 30 subjects who completed the above instruments before May 1999 were included in the study. The results suggest that close to 50% of their meal compliance can be explained by variations in four explanatory variables: gender, ineffectiveness, interoceptive awareness and distrust. The adjusted r2 was 0.497 and the significance of the equation, measured by the p value, was p = 0.0002. We conclude that multiple regression analysis is a valuable tool to identify patients' traits with the strongest effect in meal compliance. PMID- 11216128 TI - The Eating Disorder Inventory in evaluation of impaired eating behaviour in subjects requesting nutritional consultation. AB - The present study evaluated impaired eating behaviour in women seeking participation in a diet-based programme of weight reduction or achievement of ideal body weight. Forty-seven obese, 42 overweight and 14 normal-weight subjects, attending an Italian university outpatient clinic completed the Eating Disorder Inventory (EDI). Forty-eight mothers of primary school children (25 normal-weight and 23 overweight) were used as controls. The EDI consists of 8 subscales, 3 evaluating psychopathology related to eating disorders (drive for thinness, bulimia, body dissatisfaction) and 5 evaluating general psychopathology (intereoceptive awareness, ineffectiveness, maturity fears, perfectionism, interpersonal distrust). Significantly altered scores in the first three subscales were observed both in normal-weight and overweight outpatients compared to the controls. The overweight outpatients scored higher than the obese patients in terms of drive for thinness and bulimia and higher than the normal-weight women for terms of bulimia, body dissatisfaction and drive for thinness. The overweight controls scored significantly higher than the normal-weight controls in the first three subscales in the remaining subscales, mean values were also higher in the overweight group, though significance was only reached in the interpersonal distrust and interoceptive awareness subscales. Impaired eating behaviour is frequent in subjects seeking participation in weight reduction or ideal body weight achievement programmes. PMID- 11216126 TI - Eating disorders in the Far East. AB - OBJECTIVE: To investigate eating disorders (EDs) prevalence rates among Asian populations and identify characteristics that distinguish them from their Western counterparts. METHOD: Potential references were identified through an English language literature search using Medline, Psychinfo, Dissertation Abstracts (1966 to 1999) and through extensive manual searching of textbooks, reviews and reference lists. RESULTS: The majority of studies related to EDs were conducted in Japan and China and a few were conducted in Singapore, Malaysia, Taiwan, and Korea whereas there was none in the Philippines, Laos, Vietnam, Cambodia, Myanmar, Indonesia and Thailand. Prevalence rates in Japan range from 0.025 to 0.030% for anorexia nervosa (AN) and from 1.9 to 2.9% for bulimia nervosa (BN). Community studies in China have found the AN prevalence to be 0.01% and BN rates ranging from 0.5% to 1.3%. These rates are lower than ED rates in the West (particularly the U.S. and Britain). Body dissatisfaction (BD) and dieting rates, however, were similar to those in the West. BD rates ranged from 68% (Taiwan) to 81% (Korea) and dieting rates ranged from 34% (Taiwan) to 68% (Japan). Sociocultural and developmental risk factors were relevant to this population. CONCLUSIONS: EDs in Asian populations have received little attention because they have been predominantly viewed as associated with Western culture. Classified by many as a "culture-bound syndrome" of the West, they may really be a culture change syndrome. PMID- 11216129 TI - Hospital admission and mortality rates in anorexia nervosa: experience from an integrated medical-psychiatric outpatient treatment. AB - OBJECTIVES: To evaluate the effectiveness of an integrated medical-psychiatric treatment of major eating disorders. DESIGN: Historical cohort study. SETTING: Outpatient Unit for Protein Energy Malnutrition of the Department of Clinical and Experimental Medicine, "Federico II" University of Naples, time of study: January 1994 to December 1997 PARTICIPANTS: 147 female patients with restrictive or bulimic anorexia nervosa (mean age 19.8 +/- 13.7, BMI 14.7 +/- 2.1 Kg/m2) consecutively attending the outpatient unit between January 1994 and December 1997. MAIN OUTCOME MEASURES: Hospitalization and mortality rates were evaluated up to Jan 1999 with a minimum follow-up of 18 months. RESULTS: There were 23 admissions to the Clinical Nutrition ward for 19 patients (i.e. 12.9%) mostly due to severe protein energy malnutrition, and 2 deaths, only 1 strictly related to anorexia (mortality rate 0.7%). CONCLUSIONS: Integrated outpatient medical psychiatric treatment for major eating disorders is an effective and inexpensive procedure that reduces mortality and admissions due to medical complications in the medium term. PMID- 11216131 TI - Interdisciplinary team for the treatment of eating disorders. AB - Eating disorders are pathologies with a complex, multifactorial etiopathogenesis. Their treatment requires an interdisciplinary team. This paper discusses some characteristics and the most common difficulties encountered by such a team (multiple transfers, concealed alliances, role inversion, dissociation). Since their task that is carried out with patients in a critical situation and conflicting families, the team members are exposed to stressing conditions (illustrated by their dreams), and faced with possibilities of withdrawal and/or burn-out. PMID- 11216130 TI - The compliance of hypocaloric diet in type 2 diabetic obese patients: a brief term study. AB - In studies of the effect of diets in obese type 2 diabetic patients, information about the degree of compliance or non-compliance is generally lacking or incomplete, though their poor long-term success rate is widely recognized. We have quantified the degree of short-term compliance with a personalized hypocaloric diet (800-1500 kcal) in 77 obese type 2 diabetic patients (mean age 60, mean BMI 34.4) three months after explaining their dietary schedule and its expected advantages by means of simple but essential nutritional advice lasting about 20 minutes of the type currently used for such patients attending diabetes care institutions or outpatient departments. Even though a mean 14% reduction in daily food intake was achieved, the mean daily energy intake at the interview (assessed by means of the 3-day recall method) still exceeded the prescribed diet by 40-50%. The worst compliance in terms of total excess energy intake or carbohydrate and fat intake was found in the older patients. The greater the excess of food intake, the poorer the metabolic control, as expected. PMID- 11216132 TI - Gastrointestinal complications in a patient with eating disorders. AB - Eating disorders are frequently observed in young people. They can induce major complications involving several organs, either directly or through protein energy malnutrition. Gastrointestinal problems are the most common and somewhat different in restrictive and bulimic anorexia. Delayed gastric emptying prevails in restrictive anorexia, with slower intestinal transit and atrophy of the smooth muscles of the gastrointestinal tract. In bulimic anorexia, vomiting is the cause of several oesophageal and gastric lesions, from oesophagitis to perforation of the oesophagus or stomach. C.G. is a 16-year old boy who weighs 41.8 kg, is 174 cm tall and has a BMI 13.7 (kg/m2). At 14 he started to suffer from restrictive anorexia, then bulimic anorexia for the last two months. The day before admission, the patient ate a large quantity of "sfoglia-telle" in about 2 hours during a bulimic crisis. After 8 hours, he had spontaneous vomiting, malaise, abdominal tension and slight mental confusion. Physical examination showed a tense and tender abdomen with infrequent peristalsis, mental confusion and dehydration. Laboratory evaluation confirmed dehydration (serum albumin 5.7 g/dL); a plain abdomen film showed marked gastrectasia. Instrumental examinations (abdominal CT scan, upper endoscopy) confirmed the diagnosis of gastrectasia with tight pyloric stenosis. PMID- 11216133 TI - Conditions predisposing to maternal mortality in twins and singletons, US birth cohort 1989. AB - Twin pregnancy is one of the most important conditions associated with increased perinatal mortality and morbidity. The consequences of twin pregnancy on the mother have not been explored in great detail. The aim of this study was to analyze the population-based data from the United States and delineate the various conditions of twin pregnancies which predispose to maternal mortality. Results of this study show that multiple pregnancy is strongly associated with maternal mortality and requires further analysis in order to prepare appropriate therapeutic and prophylactic protocols. PMID- 11216134 TI - Zygosity of twins: is it time for a new terminology? AB - The term zygosity reflects the origin of twins--when twins are monozygotic, they are derived from a single fertilized ovum; when twins are dizygotic--the come from two fertilized ova. Zygosity assessment seemed straightforward 50 years ago. Currently, as more information and more technology becomes available, zygosity testing becomes a real problem. It is important to realize the importance of correct zygosity testing not only in the antepartum care of the pregnant mother, but more importantly--during the whole lifetime of twin individuals. This paper discusses revolving around zygosity, methods of assessment, their limitations and proposes new terminology which incorporates the recent knowledge about early human development. PMID- 11216135 TI - Perinatal management and problems of preterm twins less than 32 weeks of gestation in Japan. AB - Between 1983 and 1998 there were 23433 births at Kitasato University Hospital, including 359 births. A retrospective analysis was performed on 320 twin pairs analyzing survivability indexes with respect to fetal age, chorionicity and birth weight discordance. Furthermore, the paper illustrates an analysis of causes of neonatal deaths as well as the rate of various complications of twins delivered before 32 weeks gestation such as twin-twin transfusion syndrome and periventricular leukomalacia. PMID- 11216136 TI - [Possibilities and applications of pulse oximetry during labor]. AB - Fetal pulsoxymetry gives the opportunity of constant registration of oxygen saturation in the fetus during delivery. Important changes of the utilized equipments are crucial for proper assessment of this parameter. Construction of the sensors is of special importance. A good fixation of the sensors is prerequisite for the avoidance of artefacts. So far this procedure has not been used for diagnosing threatened fetal hypoxemia. Recent clinical research shows that the above method reflects a good state of the fetus if only good quality of signal and constant high saturation is maintained. That is why the method helps in the case of suspicious cardiotocographic records. Besides the application in fetal arrhythmias, the method can be used to decrease the number of blood gas analyses. The quality of pulsoxymetry should be confirmed by prospective studies in the nearest future. PMID- 11216137 TI - [Peculiarities of multiple pregnancy: epidemiology]. AB - The epidemiology of multiple pregnancy is complex and depends on various factors including age, race, genetic and environmental factors, season of conception and, more recently, iatrogenic factors. In recent years, twinning rate increased dramatically especially in countries where ovulation induction and assisted reproductive technologies are widely used. Multiple pregnancies are most frequent in Nigeria where majority of them are dizygotic. The lowest frequency of twinning is observed in Japan where almost 70% of multiples are monozygotic. This paper discusses genetic, environmental and sociocultural factors which are related to the "epidemic" of multiples. PMID- 11216138 TI - [Peculiarities of multiple pregnancy: embryology]. AB - Multiple pregnancies are not physiologic in humans and the understanding of the pathogenesis of this phenomenon is not fully established. Embriology of multiple pregnancy has been extensively investigated and this paper presents the phases of embrional development of monozygotic and dizygotic twins. PMID- 11216139 TI - [Peculiarities of multiple pregnancy: diagnosis]. AB - Before ultrasound was aggressively introduced into everyday obstetrical practice, diagnosis, prophylaxis and active pre- and perinatal management were at best inadequate, but more often nonexistent. Twin pregnancies were complicated by high perinatal morbidity and mortality. The use of classical radiography was limited due to proven teratogenic and carcinogenic properties. Introduction of ultrasound dramatically changed the obstetrician's approach to twin pregnancy management. This paper discusses in detail the recent advances in ultrasound diagnosis of twin pregnancy. PMID- 11216140 TI - [Peculiarities of multiple pregnancy: complications]. AB - Multiple pregnancies are considered high risk. This qualification is associated with the multitude of conditions which are known to complicated these pregnancies. Early diagnosis of these complications is the fundamental element of clinical managements. In numerous cases therapeutic protocols are widely known and in many others intensive monitoring and appropriate management may save the fetus from early and late complications. This paper will discuss the most common prenatal and perinatal complications associated with multiple pregnancies as well as the most widely accepted therapeutic protocols. PMID- 11216141 TI - [The influence of infertility treatment and assisted reproduction techniques on multiple pregnancy rates]. AB - It has to be remembered that pregnancies resulting from assisted reproductive technologies are more complicated that spontaneous pregnancies. There are higher rates of spontaneous abortions, ectopic, and multiple pregnancies. This work summarizes the latest year's experiences from the best world's clinics with multifetal pregnancy incidence in assisted reproductive technologies programs. PMID- 11216142 TI - [Maternal weight gain during twin pregnancy. Its relationship to the incidence of preterm delivery]. AB - OBJECTIVES: To determine maternal weight gain curve for twin gestation and to examine the risk of preterm birth associated with rates of weight gain (kg/week) to and from 24 weeks to delivery. PATIENTS: This study involved analysis data collected retrospectively on a cohort of women who received prenatal care from Outpatient Department for Women in Czechow district in Lublin, from 1986 to 1998. The study sample included 39 twin pregnancies. 12 (30.8%) women delivering twins before 37 weeks. METHODS: Gestational age was estimated from first day of last menstrual period. Information on prepregnancy weight was obtained by interview at the first prenatal visit. Weight gain was expressed in several ways: 1) For the descriptive analysis of weight gain by gestational age, the woman's pregravid weight was subtracted from the weight measured at each visit. 2) The weekly rate of weight gain was calculated by dividing the amount of weight gained between visits by the number of weeks during the time interval. Then we calculated the mean weekly rates before and after 24 weeks for each individual. RESULTS: Weight curve in group of women pregnant with twins showed similar linear trends. In women delivering twins before 37 weeks, the rate of weekly gain to and from 24 weeks to delivery was lower (statistically nonsignificant) when compared with mothers delivering at term (0.38 versus 0.53 and 0.58 versus 0.69 kg/week, respectively). CONCLUSION: The results suggested, that spontaneous preterm delivery was associated with lower rate of weight gain before and after 24 weeks. PMID- 11216143 TI - [Analysis of premature twin pregnancies and deliveries]. AB - Preterm labor is the most frequent complication of twin gestation. Between 1988 1998, 123 twin pregnancies complicated by preterm labor were observed. Complications during pregnancy, mode of delivery, neonatal outcomes, mortality and morbidity were presented. We compared our outcomes to data from current literature. PMID- 11216144 TI - [The role of ultrasonographic evaluation of uterine cervix length and dilation for diagnosis and management of twin pregnancy]. AB - OBJECTIVE: This study assesses ultrasonographic parameters concerning cervix length and cervical canal width of women with bigeminal pregnancy. The parameters mentioned proved to be useful while taking a right therapeutical decision i.e. using tocolysis or surgical treatment (cerclage). MATERIALS AND METHODS: This study included 52 women with bigeminal pregnancy. There were 14 women with the first pregnancy and 38 with the second and more pregnancies--ranging from 18 to 35 years of age. The negative obstetrics past and non-invasive treatment as well as surgical treatment were taken into consideration. 43 women were diagnosed using ultrasonographic examination. The cervix length and cervical canal width were checked every 7-14 days. In 9 of them the cerclage was done. RESULTS: In the group of women with cerclage 66.6% of pregnancies ended before the 37th week. The mean pregnancy duration was 29.4 weeks. 46.3% of infants were discharged in satisfactory condition. In the other group (tocolysis) 54.8% of pregnancies ended before 37th week. The mean pregnancy duration was 34.2 weeks. 72.7% of infants were discharged in satisfactory condition. CONCLUSIONS: The assessment of the length of the cervix and the width of the cervical canal in the bigeminal pregnancy by the case examination is performed in order to take proper therapeutical decisions i.e. tocolysis or surgical treatment. PMID- 11216145 TI - [Levels of tumor necrosis factor-alpha and interleukin-2 in sera of twins delivered prematurely and at term]. AB - The concentration of tumor necrosis factor-alpha (TNF-alpha) and interleukin-2 (IL-2) was estimated in first day of live in sera of premature (n = 8 pair) and in term delivered twins (n = 12 pair). One of premature delivered newborns was born vaginally 48 hours after first twin. Concentrations of TNF-alpha were approximately 4-times higher in sera of premature delivered in comparison to term delivered twins and a highest, more than 5-times higher level, was detected in serum of premature newborn born a 48 hours after first twin. Concentrations of IL 2 in sera of premature delivered were approximately 2.5-times higher than in term delivered twins and not significantly variations were observed in delayed delivered twin. PMID- 11216146 TI - [Analysis of twin pregnancies in material from the Department of Obstetrics and Pathology of Pregnancy in Lublin from 1991-1998]. AB - The course of multiple pregnancies and multiple fetus labor were analyzed in 111 women delivered in the Department of Obstetrics, School of Medicine in Lublin in the years 1991-1998. It has been found that the most frequent patients were those aged 25-29 coming from the cities and after the infertility treatment. The aim of this research was to characterize twin pregnant patients, and present the outcome of multiple pregnancy. The studies were performed on 67 women from the cities and 44 women from the villages. It is significant that almost 55% pregnant women underwent the cesarean section and their average birth weight was 2490 g. These results indicate that multiple pregnancy is in high risk pregnancy. PMID- 11216147 TI - [Triplet pregnancies in materials from the Obstetrics and Perinatology AM in Lublin in 1989-1999]. AB - A retrospective analysis of 14 triplet pregnancies at the Department of Obstetrics and Perinatology, University School of Medicine in Lublin, from January 1, 1989 to June 30, 1999 was undertaken. All pregnancies were ended by cesarean section. No difference in Apgar score and in average birth weight between I, II and III foetus was observed. The mean hospitalisation time for mothers was 32.5 +/- 29.01 days and the mean gestational age at delivery was 32.14 +/- 3.44 weeks. The indication for cesarean section in all cases was triplet pregnancy and additional complications: threatened intrauterine infection, threatened intrauterine asphyxia, abruptio placentae, preterm labour. Perinatal mortality rate was 12.82%. PMID- 11216148 TI - [Analysis of prognostic factors in a group of infants from multiple pregnancy and very low birth weight]. AB - Preterm birth remains a major cause of perinatal morbidity and mortality. The purpose of the study was to examine factors influencing on the survival and early prognosis of very low birth weight premature infants in multiple gestation born at the Department of Obstetrics and Perinatology University School of Medicine in Lublin. Congenital malformations were excluded from the study. CONCLUSION: In this retrospective analysis the reduction in the incidence of respiratory distress syndrome in multiple gestation was observed. Survival was significantly correlated to prenatal corticoid prophylaxis, Apgar score and lack of the respiratory distress syndrome. The mortality showed an inverse correlation to birth weight and age of gestation. PMID- 11216149 TI - [Twin pregnancy complicated by "twin reversed arterial perfusion" syndrome]. AB - We have reported twin pregnancy complicated by uncommon "twin reversed arterial perfusion" syndrome. Ultrasound scan at 27th week of gestation revealed one normal foetus and the second one "acardiac" with severe malformations. Since the cardiac failure of the first twin was observed, the digitalis were administered till the end of pregnancy. The pregnancy was terminated at 31st week by caesarean section. We succeed in delivering one healthy newborn, which was possible by appropriate management including elective termination, observation (ultrasonography and cardiotocography) and nonsurgical intervention (digitalis). PMID- 11216150 TI - [Cesarean section for the second twin during the course of delivering twins]. AB - We have analysed 6 cases of twin pregnancies with vertex presentation of the first foetus. In this cases after delivery of the first twin by vaginal route caesarean, section was made. Caesarean section of the second twin was made because of: transversal presentation with fetal distress syndrom (four cases), umbilical cord drop (one case), and premature placenta ablation (one case). We have determined acid base balance and Apgar score. We have noted worse results for the second twin, independently too of the time between deliveries both twins. Caesarean section of the second twin is the rarely clinical situation, but in motivated situation is accepted and reasonable solution. PMID- 11216151 TI - [Multiple pregnancy in the Obstetrics and Perinatology AM in Lublin in 1989 1999]. AB - A retrospective analysis of 400 twin and 14 triplet pregnancies at the Department of Obstetrics and Perinatology, University School of Medicine in Lublin, from January 1, 1989 to June 30, 1999 was undertaken. A number increase of multiply pregnancies was observed--from 124 in the period 1989-1992 to 181 in the period 1996-1999. A percentage increase of cesarean sections was observed--from 52.42% to 77.34% respectively. The most frequent indications for the cesarean sections were non-vertex presentation of the first twin, threatened intrauterine infection and threatened intrauterine asphyxia. PMID- 11216152 TI - [Breast feeding of twins with regard to pre-term infants]. AB - The benefits of breast-feeding for health and development pre-term and full-term infants changed the attitude towards nutrition of twins and higher-order multiples. Mothers of twins are often at risk of unsuccessful initiation of lactation while in hospital. The possibilities to provide appropriate intervention and support when a mother breastfeeds twins are presented. PMID- 11216153 TI - [The significance breast feeding on the course of the adaptation period in neonates from multiple pregnancies]. AB - Neonates from multiple pregnancies were evaluated taking into account their condition in the 1st and 5th minutes after birth, their birth weight, time which they spent in the neonatal department and occurrence of complications during the adaptation period, such as respiratory insufficiency, intrauterine infection and hyperbilirubinaemia. On the basis of our research, we think that multiple pregnancy requires particular diagnostics and individualisation of prenatal care. We believe also that neonates from such pregnancies are particularly exposed to development of a severe form of diverse complications. In our investigations, we observed a beneficial influence of breast-feeding--from the first hours of life- on the course of adaptation of neonates. However, we think that confirmation of these findings requires more detailed investigations. PMID- 11216154 TI - [Delivery of twins by Cesarean section with the Misgav Ladach method]. AB - Between September 1998 and July 1999, 34 patients with twin pregnancy (79.1%) underwent cesarean section with Misgav Ladach method in the Department of Obstetrics and Perinatology of the Medical Academy in Lublin. The aim of this study was to evaluate safety and other advantages of the Misgav Ladach method. Body temperature, usage of antibiotics, analgesics, hematinics, and postoperative complications were evaluated in the postoperative course. No postoperative complications were noted at 32 patients (94.1%). 67.6% of patients did not receive antibiotics. Stitches were removed on the fourth p.o. day at 70.6% of patients. This study highlights the safety of the Misgav Ladach method, and points out some advantages like reduction of postoperative pain, speeded recovery, and no indication for transfusion. PMID- 11216155 TI - [Twin pregnancy and preeclampsia]. AB - INTRODUCTION: Preeclampsia is a pregnancy-specific disorder of humans which rates among one of the major cases of maternal and fetal morbidity and mortality. Etiology of preeclampsia is still largely unraveled and treatment is syndrome specific. OBJECTIVE: Evaluation of the incidence of preeclampsia in twin pregnancies and comparison of selected clinical characteristics among preeclamptic and non-preeclamptic twin pregnancy patients. METHODS: Retrospective analysis of 194 normotensive and 25 preeclamptic patients with twin pregnancies admitted to the Lublin State Hospital Nr 4 between January 1st 1992 and December 31st 1997. Patients were matched for gravidity, parity, maternal age and selected biochemical parameters. RESULTS: Preeclampsia occurred two times more frequently in nulliparous women (68% vs 32%). Gravidas with preeclampsia had significantly higher serum uric acid levels than their non-preeclamptic counterparts (6.7 +/- 0.3 vs 4.3 +/- 0.1; p < 0.001). Hypertension, proteinuria and edema coexisted concomitantly in 52% of preeclamptic patients. CONCLUSIONS: 1. Preeclampsia complicates one tenth of twin pregnancies. 2. In preeclamptic women nulliparas were two times more frequent. 3. In preeclamptic women is significantly higher level of uric acid. PMID- 11216156 TI - [Analysis of the frequency of diseases during twin pregnancy, methods of its completion and complications ascertained in newborns from personal clinical materials]. AB - One analysed course 49 of pregnancies and labours, which one took place in Clinic of Obstetrics Medical Academy in Bialystok in years 1997-1999. Most frequent complication of bigeminal pregnancy was premature labour (53.1%). Considerable percentage of gemellary pregnancies was delivered of caesarean section. In chances of pregnancies finished before term--62% and 57% in pregnancies finished in term. Indication to caesarean section was most often threatening intrauterine infection of embryo at premature departure amniotic fluid in premature delivery and complications of preeclampsia in delivery at term. Labour in operating way was more profitable for new-born child than childbirth ways of nature. PMID- 11216157 TI - [Complications of multiple pregnancy in the 2nd and 3rd trimesters]. AB - Multiple pregnancy contributes to higher maternal and fetal risks than a single one. Complications typical only for multiple pregnancy such as PROM with preterm delivery, intrauterine death or IUGR of one of twins can occur during 2nd and 3rd trimester. Treatment in such situations is usually difficult and often controversial because of simultaneous presence of an alive and/or healthy fetus and possible risk for mother. The paper presents such situations and possible ways of treatment. PMID- 11216158 TI - [Triplet gestation--analysis of pregnancy course, delivery and neonatal outcome, based on personal material]. AB - Triplet gestation appears in 0.1-0.3% of all pregnancies and it is high risk pregnancy for mother and foetus. It appears more frequently in Afroamerican women, rarely in Japan women. In multifetal pregnancy early prenatal diagnosis and management are very important. AIM: Analysing course of pregnancy, way of delivery, condition of newborns, influence of environmental factors, and concomitant diseases in triplets gestation. MATERIAL: 30 women treated between 1989-1998, in Division of Perinatology, University of Medical Sciences in Poznan, Poland. RESULTS: 21 pregnancies were ended by caesarean section, 9 by vaginal delivery. Apgar score for II and III foetus decreases significantly. pH value of umbilical artery was without significant differences. CONCLUSIONS: Almost all triplets have ended preterm. Route of delivery of triplets have to be considered individually. Environment factors could play an important role in multifetal pregnancy. PMID- 11216159 TI - [The influence of delivery methods for twins on obstetric results]. AB - The analysis covered 100 twin gestations over the years 1996-1998 in the material of Gynecology and Obstetrics Clinic in Bydgoszcz. The authors estimated the relations between the mode of delivery and presentations of the twins. Abnormal foetal presentation occurred in 68 pregnancies (68%), and was more often in the second twin (61.8%). The highest percentage of cesarean sections (29%) we have observed in the case of an abnormal presentation of the first twin. The condition of the twins in their first minute after the birth was estimated according to the birth weight, the gestational age, and the mode of surgical procedures performed. Better condition after the birth of the second twin with the birth weight above 1000 g comparing to the first twin was established in cesarean sections, not in other obstetrical procedures. There was no essential difference between the mortality rate of the first and the second twin. Early diagnosis of the twin pregnancy using USG helps us to choose a suitable management during pregnancy and an optimal mode of delivery. PMID- 11216160 TI - [Ultrasonic diagnosis in the first trimester of multiple pregnancy]. AB - Higher rate of morbidity and mortality has been noted in tween pregnancies comparing to singleton pregnancies. Early ultrasound investigation between 6 and 12 week of gestation is useful in determining time of gestation, amniocity and chorionicity (adequacy of diagnosis ranged from 95 to 100%). Determining of chorionicity and amniocity is extremly important in monozygotic twins, because of high risk of complications during next stages of pregnancy. First trimester ultrasound investigation allows to define abnormalities commonly associated with twin pregnancy and is useful in monitoring of fetal well-being. PMID- 11216161 TI - [Multiple pregnancy as a cause of premature delivery]. AB - Authors analysed management, complications and outcome of 13 multifetal pregnancies (11 triplet and 2 quadruplet), their duration, the way of delivery, indications for cesarean section and perinatal mortality rate. A majority of the multifetal pregnancies were diagnosed before the end of 20 weeks gestation, and 69.2% of women had cervical cerclages. Tocolysis was used in 9 cases (69.2%). The mean gestational age at delivery was 32.8 weeks. Cesarean section was performed in nine cases (29 neonates). Of the 41 neonates there were 2 stillbirth (4.88%) and 3 neonatal death (7.31%). In 87.9% of cases, delivery occurred before the end of 37 weeks gestation. The most common maternal complications were toxemia (23.1%) and anemia (46.2%). PMID- 11216162 TI - [Prenatal diagnosis in twin pregnancy]. AB - There are some unique problems of prenatal diagnosis and genetic counselling of twins, although methods of evaluation are similar in multiply and singleton pregnancies. Indications, risk and complications of this techniques were described. Also sensitivity and specificity of biochemic screening examination were compared between singleton and multiply pregnancy. Prenatal diagnosis based on amniopunction and chorionbiopsy seems to be safe and useful method determining aneuploidy. The risk of this methods is higher in twins than in singleton pregnancies. Although, in twin pregnancies, it is related rather to higher complications rate, than to procedures pregnancies losses. PMID- 11216163 TI - [Mode of delivery in twin gestations from material at the Department of Obstetrics in the District hospital of Lublin]. AB - The aim of this study was to review 39 twin deliveries in the Department of Obstetrics in District Hospital in Lublin in 1998. The incidence of twin pregnancies was 2.01%. Eighteen patients (46.15%) were term at delivery whereas 21 (53.8%) were premature (mean gestational age at delivery 35 weeks). Vertex presentation of both twins was the most common with an incidence of 48.7% followed by vertex-nonvertex (25.6%) and non-vertex presentation of first twin (15.4%). Twenty patients (51.28%) delivered vaginally and 19 women (48.7%) underwent cesarean section including 2 cesarean birth of second twin after vaginal delivery of first twin. In our results, we conclude that the techniques of twin delivery, whether vaginal or by cesarean section, would depend on the judgement and expertise of the labour in twin gestations. PMID- 11216164 TI - [Twin pregnancy complicated by intrauterine death of one twin]. AB - In twin pregnancies single intrauterine death of one fetus is associated with significant morbidity and mortality of the surviving infant. The aims of our retrospective study were to review conditions of twin pregnancies complicated with SIUD in Polish Mother's Memorial Hospital in Lodz between 1989-1999 and to assess the fetal outcome when conservative management had undergone. In this study we reviewed 30 twin gestations involving the intrauterine death of one fetus. The incidence of preterm delivery among pregnancies with fetal death was 83.3%; Caesarean section was the method of delivery in 53.3% cases. Monochorionic placentation was found in 60%. Conservative management until there is no risk for the fetus is apt. PMID- 11216165 TI - [Risk of preterm birth in twin pregnancy]. AB - The aim of the study was to analyze the selected risk factors in twin pregnancies. Retrospective analysis was carried out in the Research Institute Polish Mother's Memorial Hospital (ICZMP) in Lodz and covered data from the period of time between 1989-1999. Out of 38,066 deliveries which had place in the ICZMP 538 twin pregnancies were enrolled in the study. We evaluated usual risk factors for preterm birth such as body mass index, short cervical length, beta mimetics admission, presence of bleeding and contractions as well as socio demographical characteristics such as age, parity, martial status and educational level. Univariate analysis and ?2 test were preformed. Odds ratios and 95% confidence intervals were calculated. For multivariate analysis logistic regression model was used. Most of the risk factors for preterm birth were not significantly associated with spontaneous preterm birth of twins. PMID- 11216166 TI - [Perinatal outcome in multiple pregnancy after natural reproduction and ART techniques]. AB - In this study we analysed occurrence of multifetal pregnancy in groups of patients after natural reproduction and after using ART between 1991-1998 in clinical material. We showed the most important complications during pregnancy, occurrence of TTTS, percentage of prematurity, percentage and indications to caesarean sections. We found that above-mentioned manifestations of perinatal care were comparable with reports of Polish and foreign authors. PMID- 11216167 TI - [Term delivery in twin pregnancy]. AB - We analyzed the data on 55,839 births that taken place in 1998 year in the southeast region of Poland. The incidence of twin pregnancy was about 1%. A half of them delivered before 259 day of gestational age, the beginning of birth occurring norm for human. This means that onset of this norm for singleton pregnancies is the mean of 12 weeks births occurring norm (215-303 days of gestational age) for multifetal pregnancies simultaneously. The particular meaning has prevention of preterm delivery and in this case the computer-aided monitoring of pregnancy and prediction of birth date is a very useful invention. PMID- 11216168 TI - [Selective salpingography in cases of proximal tubal occlusion]. AB - The technical performance and results of selective salpingography (SGS) in 28 infertile women with proximal tubal occlusion (PTO) are presented. In 50 cases of PTO, diagnosed first by hysterosalpingography (HSG) and/or laparoscopy, 14 oviducts (28%) were patent during initial HSG using the baloon catheter tightly filling the internal cervical orificium and from remaining 36 tubes 27 (75%) were successfully recanalized by SGS. Three patients after successful SGS became pregnant. One of the pregnancies was ectopic. The SGS should be widely accepted in diagnosing and treatment of PTO as a cheap, simple, noninvasive and very effective method. PMID- 11216169 TI - [The value of computerized topographic evaluation for CIN changes in the cervix of young women based on effectiveness of CO2 laser therapy]. AB - OBJECTIVES: Cervical cancer is one of the commonest neoplasms occurring in the female population of Poland. The discontinuance of radical treatment in CIN (Cervical Intraepithelial Noeplasia) cases for several years now is of particular importance for young women who are still in the reproductive age. DESIGN: The aim of the study was to evaluate early changes in the epithelium of the cervix by means of computer analysis of the fluorocolposcopic pattern. MATERIALS AND METHODS: The study included 164 young women (out of 2,098 women with cervical lesions) aged 18-35 years with a diagnostic of incipient CIN I-III changes in the cervix. The precise topography of the lesions was determined in fluorocolposcopy by the Berthalanffy technique using acridine orange. In the method the fluorocolposcopy made by "Polskie Zaklady Optyczne" was used. The analysis of the picture was made on the basis of a "MicroScan" programme. The florocolposcopic ones was transferred directly to the IBM Pentium II computer by means of a highly sensitive colour CCD OSCAR 35 camera. The image analysis was made simultaneously using a monochromatic camera CCD 6012P basing on a defined scale of greyness that corresponded to the luminescent of the method. The patients were treated exclusively with CO2 laser in the clinical reference centre. RESULTS: Of all the patients treated, a cure after one application of CO2 laser was achieved in 94.6%. 1 women with a pretreatment diagnosis of a CIN III lesions required further therapy. In all the 9 women (5.4%) requiring also further treatment, the degree of progression of the lesions was never greater than that found in the pretreatment evaluation. CONCLUSIONS: Extended colposcopic techniques (especially fluorocolposcopy) give a good insight into the biology of tissues involved in CIN processes. The introduction of computer analysis of fluorocolposcopic patterns permits precise determination of the topography of the lesions; especially to increased the efficacy of destructive treatment by CO2 laser. After the introduction of computer techniques in evaluation patterns of lesions, the efficacy of CO2 laser treatment of CIN lesions in young women is expected to rise to 99%. PMID- 11216170 TI - [The value of serum tissue polypeptide specific antigen TPS concentration in therapeutic monitoring of patients with epithelial malignant ovarian neoplasms]. AB - DESIGN: The aim of this study was compare the concentrations TPS and CA 125 in serum 37 patients with ovarian carcinoma in order to evaluate the usefulness of markers in monitoring therapy. MATERIAL AND METHODS: The concentrations of TPS and CA 125 were determined prior to surgery, 1 week after surgery, prior chemotherapy, after 3 and 6 course chemotherapy next every 3 months for the first year and every 6 month for the next 2 years. RESULTS: The concentration of TPS decreased above cutoff values in all patients with remission after 3 course chemotherapy, CA 125 after 6 course chemotherapy. In patients with remission the increase of TPS preceded 3 to 12 months, of CA 125 1 to 3 month the reoccurence of the disease. In of patients with progressive disease the TPS levels decreased during therapy and next rise. CONCLUSIONS: The current observations demonstrate that serial measurements of TPS appear to be useful for the evaluation of therapy and monitoring of patients. PMID- 11216171 TI - [Analysis of effectiveness for treating endometriosis with a Synarel (acetate naphareline) preparation]. AB - The aim of the work was estimation of effectiveness of Synarel preparation in the treatment of pelvic pain syndrom caused by endometriosis, and assessment of remission of endometriosal focuses, situated in the small pelvis. Examination were performed on 10 cases which were divided into two groups. First of them the group of 6 patients with the intensive premenstrual pain complaints. The second group involved 4 patients with the little subjective pain ailments, which were treated for sterility. The patients were qualified for the 6-months Synarel treatment in according to the grade of intensification of endometriosis. The studies proved that Synare therapy was well-tolerate and effective in the treatment of intermediate and low-advanced cases of endometriosis with pelvic pain complaints. PMID- 11216172 TI - [Abrikosov's tumor of the vagina--clinical case report]. AB - OBJECTIVES: Granular cell myoblastoma (Abricosov's tumor) is an uncommon benign tumor of mesodermal origin of which no more than sixty cases with genital involvement have been reported. Among the genital organs, the labium majus of the vulva are the predilect site. STUDY DESIGN: The authors describe a case of the Abricosov's tumor in woman aged 58 years which became directed to Department of Gynecology & Obstetric in Hospital of Slupsk on account suspicions of vagina tumor. RESULTS: The origin and nature of granular cell myoblastoma have been debated since the original description of a granular cell tumor by Abricosov in 1926. Many cell types have been implicated in its histogenesis, including muscle cells, histiocytes, fibroblasts, neural sheath cells and undifferentiated mesenchymal cells, but the origin of the lesion remains still controversial. It is rarely diagnosed clinically and frequently discovered only as an incidental finding on physical examination. It usually occurs in the tongue, skin, breast, or subcutaneous tissue and very rarely in genital organs. Treatment remains controversial, but most studies suggest surgical or endoscopic resection as the treatment of choice. The prognosis is good but is dependent upon complete removal. PMID- 11216173 TI - [Recommended procedures in cases of suspected fetal/newborn malformation]. PMID- 11216174 TI - [Report from the III Conference on bacterial vaginosis-2000 September 14-17 YSTAD -Sweden]. PMID- 11216175 TI - Psychosocial issues in transplantation. PMID- 11216176 TI - A center-based approach to a transplant employment program. AB - The return to work after transplantation has been actively discussed in the transplant community for years. However, despite the desire for transplant practitioners to have recipients return to being healthy, contributing members of society as well as return to work, practitioners often passively support the sick role. We discovered that patients who are returning to work after transplantation may have been out of the work force for several years, and require assistance that we as healthcare providers were unable or untrained to provide. An employment specialist was added to the transplant staff and became a vital part of our attempts to create a proactive employment atmosphere and enhance our patients' quality of life. Adding an advocate for employment in our center has also facilitated the shift in our thinking and approach to care from the sick role to one of rehabilitation and from reactive to proactive. This change in attitude has assisted in empowering our recipients to feel as if they can truly resume a normal life. PMID- 11216177 TI - Xenotransplantation: the challenge to current psychosocial attitudes. AB - Because of the limited availability of transplantable human organs, xenotransplantation, the use of animal organs as an alternative source, has received considerable attention in recent years. Xenotransplantation would provide an unlimited supply of organs, and these organs would be available whenever required. Although the pig is considered the best source for organs, significant immunologic barriers currently prohibit the implementation of a clinical trial of organ transplantation. However, as medical research gains more insight into the mechanisms underlying rejection of pig organs in primates, therapeutic xenotransplantation is becoming more feasible. Clinical trials of porcine cell transplants are currently underway. Although xenotransplantation will minimize the waiting period for an organ and obviate the feelings of guilt or indebtedness commonly experienced by recipients of human organs, several psychosocial issues may hinder the reintegration of patients into society. For example, concerns that infectious pathogens could be transferred to recipients of pig organs will necessitate life-long monitoring and perhaps even temporary isolation of patients. The possible risk of the spread of a xenozoonosis from the patient to other members of the community may inspire public controversy and even fear, which may have an adverse impact on the patient's emotional state. Additionally, some patients may be psychologically disturbed by the need to incorporate pig organs into their body. This article addresses these and other psychosocial issues that may be associated with clinical xenotransplantation. PMID- 11216178 TI - Personality disorders: a challenge for transplantation. AB - Evidence concerning personality disorders is limited in the transplant literature, but the existence of a personality disorder in a transplant candidate does appear to be a risk factor for poor outcome after transplantation. This article addresses the issue of personality disorders in transplantation, including a definition and diagnostic criteria of personality disorders and the value of possible interventions to treat patients with personality disorders. Directions for treating personality disorders as part of the broader clinical management of transplant recipients are also provided. PMID- 11216179 TI - Adaptation of a weight management program for a potential lung transplant candidate. AB - Obesity is a relative contraindication for heart and lung transplantation at most transplant centers. Surgical risks are higher for obese patients, and 1 study suggests that obesity is significantly correlated with higher posttransplant death rates in cardiac transplantation. Obesity is a restrictive disease that contributes to exercise intolerance in patients with lung disease. A weight management group was formed at a transplant center to help obese patients with heart and/or lung disease lose weight and maintain their goal weight, with the hope of decreasing their waiting time to be listed for transplantation and their incidence of weight-related complications. Some patients experienced symptomatic improvement, which delayed their need for heart or lung transplantation. PMID- 11216180 TI - Social network mapping with transplant recipients. AB - Social support can have great influence on health, well-being, and general quality of life To promote awareness of the social network that surrounds each transplant recipient, transplant social workers are now using the Social Network Map as an intervention. Because perceptions of availability and accessibility of support are key elements in the use of social network resources, awakening an individual's awareness of available resources is a significant first step in enhancing social support and, ultimately, quality of life. The Social Network Map is used to establish dialogue regarding individuals' needs and sources of support, and then how the support system can meet those needs. Transplant social workers thus foster active use of those people in transplant recipients' networks who can meet the particular needs recipients identify. PMID- 11216181 TI - Mentorship programs for transplant patients. AB - The concept of mentoring has been used successfully in numerous settings, but only in the past decade have mentoring programs been used with organ transplant recipients. This paper describes how the Toronto Multi Organ Transplant Mentor Programme works, is administered, augments patient care, is evaluated, and has been adapted to meet the needs of various transplant patient populations. PMID- 11216182 TI - MD $200,000 richer after damning court judgement. PMID- 11216183 TI - Cisapride (Prepulsid): interactions with grapefruit and drugs. PMID- 11216184 TI - Pemoline (Cylert): market withdrawal. PMID- 11216185 TI - Bupropion (Zyban, sustained-release tablets): update. PMID- 11216186 TI - Diabetes in Aboriginal populations. PMID- 11216187 TI - A worthy Web site. PMID- 11216188 TI - Anticoagulant prophylaxis against stroke. PMID- 11216189 TI - Reference-based pricing. PMID- 11216190 TI - Reference-based pricing. PMID- 11216191 TI - Much ado about Furbies. PMID- 11216192 TI - Old ways of treating TB may hold new appeal. PMID- 11216193 TI - A false-positive tuberculin test result. PMID- 11216194 TI - HIV infection and risk behaviours among young gay and bisexual men in Vancouver. AB - BACKGROUND: Young gay and bisexual men may perceive that the consequences of HIV infection have dramatically improved with the availability of highly active antiretroviral therapy. We therefore sought to identify trends in HIV infection rates and associated risk behaviours among young gay and bisexual men in Vancouver. METHODS: Prospective cohort study involving gay and bisexual men aged 18-30 years who had not previously tested HIV positive. Subjects were recruited through physicians, clinics and community outreach in Vancouver. Annually participants were tested for HIV antibodies and asked to complete a self administered questionnaire pertaining to sociodemographic characteristics, sexual behaviours and substance use. Prevalence of HIV infection and risk behaviours were determined for eligible participants who completed a baseline questionnaire and HIV testing as of May 1998. The primary outcome was the proportion of men who reported having protected sex during the year before enrollment and who reported any episode of unprotected sex by the time of the first follow-up visit. RESULTS: A total of 681 men completed a baseline questionnaire and HIV testing as of May 1998. The median duration between baseline and the first follow-up visit was 14 months. The median age was 25 years. Most of the subjects were white and of high socioeconomic status. The majority (549 [80.6%]) reported having sex only with men; 81 (11.9%) reported bisexual activity. Of the 503 men who had one or more regular male partners, 245 (48.7%) reported at least one episode of unprotected anal sex in the year before enrollment; the corresponding number among the 537 who had one or more casual male partners was 140 (26.1%). The prevalence and incidence of HIV seropositivity were 1.8% (95% confidence interval [CI] 0.8% 2.8%) and 1.7 per 100 person-years [95% CI 0.7-2.7], respectively. Fifty-two (26.5%) of the 196 and 55 (29.7%) of the 185 men with regular partners who reported having practiced protected insertive and receptive anal sex in the year before the baseline visit reported engaging in these activities without a condom at the follow-up visit; the corresponding numbers among the 232 and 242 men with causal partners who had practiced protected insertive and receptive anal sex before the baseline visit were 43 (15.5%) and 26 (9.4%) respectively at follow up. INTERPRETATION: The incidence of HIV infection is unacceptably high among this cohort of young gay and bisexual men. Preliminary results suggest a disturbing trend toward increasing levels of unprotected anal intercourse. PMID- 11216196 TI - A quantitative ranking of Canada's research output of original human studies for the decade 1989 to 1998. AB - BACKGROUND: Since 1987 research articles have been catalogued with the author's affiliation address in the 40 databases of the Medical Literature Analysis and Retrieval System (MEDLARS) of the National Library of Medicine, Bethesda, Md. The present study was conducted to examine the Canadian entries in MEDLARS to interpret past and future trends and to combine the MEDLARS demographic data with data from other sources to rank Canadian research output of human studies both nationally and internationally. METHODS: The PubMed Web site of the National Library of Medicine was used to count medical articles archived in MEDLARS and published from Jan. 1, 1989, through Dec. 31, 1998. The articles attributed to Canadian authors were compared by country, province, city, medical school, hospital, article type, journal and medical specialty. RESULTS: During the study period Canadian authors contributed on average 3% (standard deviation [SD] 0.2%) of the worldwide MEDLARS content each year, which translated to a mean of 11,067 (SD 1037) articles per year; 49% were human studies, of which 13% were clinical or controlled trials, and 55% involved people aged 18 years or less. In total, 68% of the articles were by authors affiliated with Canadian medical schools; those affiliated with the University of Toronto accounted for the greatest number (8604), whereas authors affiliated with McGill University had the greatest rate of annual increase in the quantity published (8%). Over one-third (38%) of the articles appeared in Canadian journals. When counted by specialty, 17% of the articles were by authors with clinical specialties, 5% by those with surgical specialties and 3% by those with laboratory specialties. INTERPRETATION: The annual rate of increase in research output for Canada was more than 3 times higher than that seen world wide. Canada is now ranked seventh among countries contributing human studies to MEDLARS. The increase indicates that Canada's medical schools are productive, competitive in making contributions to medical science and are supporting Canadian journals. PMID- 11216195 TI - Development, dissemination, implementation and evaluation of a clinical pathway for oxygen therapy. AB - BACKGROUND: Oxygen is commonly administered to patients in hospital, but prescribing and monitoring of such therapy may be suboptimal. The objective of this study was to develop, disseminate, implement and evaluate a multidisciplinary clinical pathway for the administration of oxygen. METHODS: The authors developed a clinical pathway for the ordering, titration and discontinuation of oxygen, which was disseminated through teaching sessions, in service training sessions and information posters in a medical clinical teaching unit (CTU). Implementation of the pathway was ensured by means of reminders and patient-centred audit and feedback to CTU nurses and house staff. During a 3 month intervention phase, consecutive patients requiring supplemental oxygen were treated according to the pathway. During a 1-month "wash-out" phase followed by a 3-month non-intervention phase, patients were treated at the discretion of the CTU team. Clinical and economic data were collected in both phases. RESULTS: In the 2 phases, patient characteristics, the concentration and duration of oxygen prescribed, the frequency of oxygen saturation monitoring, the frequency of arterial blood gas testing and the clinical outcomes were similar. However, there were more discontinuation orders in the intervention phase (p < 0.001). In the intervention phase, costs were higher for monitoring of oxygen saturation ($44.95/patient v. $36.17/patient, p = 0.048) and for order transcription ($2.71/patient v. $1.28/patient, p < 0.001); total costs, including those for personnel, were also higher in the intervention phase ($76.93/patient v. $56.67/patient, p = 0.02). The cost of education about the oxygen pathway was $45.71/patient. When the education cost was included, the total cost of oxygen therapy during the intervention phase was $122.64/patient; this was significantly higher than the total cost of oxygen therapy during the non-intervention phase ($56.67/patient) (p < 0.001). INTERPRETATION: This multidisciplinary, multimethod oxygen pathway led to changes in oxygen-prescribing behaviour, consumed more resources than standard management and was not associated with changes in patient outcome. Appropriate management of oxygen prescribing and monitoring by physicians and nurses take time and costs money. PMID- 11216197 TI - Hypertension, self-perceived health status and use of primary care services. PMID- 11216198 TI - Stroke thrombolysis: is tissue plasminogen activator a defibrillator for the brain? PMID- 11216199 TI - Food irradiation: let's do it. PMID- 11216200 TI - Beyond polemic. PMID- 11216201 TI - HIV: the millennium bug. PMID- 11216202 TI - Tuberculosis: 12. Global disease and the role of international collaboration. PMID- 11216204 TI - Erythema ab igne: an old condition new again. PMID- 11216205 TI - Managing neuropsychiatric disease with transcranial magnetic stimulation. PMID- 11216206 TI - Reason for hope: the advent of disease-modifying therapies in multiple sclerosis. PMID- 11216203 TI - Causes of Alzheimer's disease. AB - It is now understood that genetic factors play a crucial role in the risk of developing Alzheimer's disease (AD). Rare mutations in at least 3 genes are responsible for early-onset familial AD. A common polymorphism in the apolipoprotein E gene is the major determinant of risk in families with late onset AD, as well as in the general population. Advanced age, however, remains the major established risk factor for AD, although environmental variables may also have some role in disease expression. Some pathogenic factors directly associated with aging include oxidative damage and mutations in messenger RNA. Other factors unrelated to the aging process may, in the future, be amenable to therapeutic intervention by way of estrogen replacement therapy for postmenopausal women, anti-inflammatory drug therapy and reducing vascular risk factors. Older theories, such as aluminum playing a role in the pathogenesis of AD, have been mostly discarded as our understanding of pathogenic mechanisms of AD has advanced. PMID- 11216207 TI - Inhaled nitric oxide for hypoxemic respiratory failure: passing bad gas? PMID- 11216208 TI - Poor penmanship costs MD $225,000. PMID- 11216209 TI - Auditor general slams feds' response to Salmonella outbreak. PMID- 11216210 TI - Caring for sick a strain on families. PMID- 11216212 TI - One HIPAA positive. Hospitals can target marketing based on patients' health background. PMID- 11216211 TI - Anthem takes steps toward IPO. Move provokes yawns from hospitals, concerns from consumers, docs. PMID- 11216213 TI - No silver bullet. Online purchasing company moves slowly in hopes of ensuring success. PMID- 11216214 TI - Chiropractors sue the Blues. Coalition accuses plans of discrimination in payments to practitioners. PMID- 11216215 TI - Turnaround, not runaround. Two systems look internally for fast fiscal fix; no scapegoat in sight. PMID- 11216216 TI - Medicare HMOs first in line. Shorted by $1 billion, health plans will ask Congress for more payment increases. PMID- 11216217 TI - Tupelo bucks the Miss. trends. Local health system provides primary care in clinics to improve public health. PMID- 11216218 TI - New doc databank open to public. $9.95 buys report from the Federation of State Medical Boards. PMID- 11216219 TI - Autopsies R Us. As hospitals, coroners change routines, private companies step in to determine causes of death. PMID- 11216220 TI - Country is king. Congress is singing a rural tune on health spending this year. PMID- 11216221 TI - Wanting more from information technology. But smaller budgets force providers to revise their expectations. PMID- 11216222 TI - The CEO who couldn't slow down retires. McMeekin follows his own principle in making room for fresh leadership. PMID- 11216223 TI - Rebuilding from within. Britain's providers helping to resuscitate public healthcare system. PMID- 11216224 TI - Shake, rattle and disenroll. Membership erodes as HMOs exit markets, but profits begin to stabilize. PMID- 11216226 TI - Why pro-lifers are missing the point. PMID- 11216225 TI - Diversity goal reached. Appointment of minorities to hospital board eases controversy. PMID- 11216227 TI - Ritalin: mom's little helper. A disorder long linked to sons migrates up the family tree. PMID- 11216228 TI - A new "time out". Parents who want to discipline their misbehaving kids should apply the hiatus to themselves. PMID- 11216229 TI - Sticks and stones. Osteoporosis can break your bones, even if you are a man. This disease is not for women only. PMID- 11216230 TI - The 'poor man's heroin'. An Ohio surgeon helps feed a growing addiction to OxyContin. PMID- 11216231 TI - Natural hazards. Tonic or toxic? Americans are gobbling up nature's remedies for everything from obesity to depression. PMID- 11216232 TI - The debt to pleasure. Explaining craving. PMID- 11216233 TI - Heart trouble could come straight from your parents. PMID- 11216234 TI - Unions. Divided they'll fall. PMID- 11216235 TI - Outpatients. A pretty little sum. AB - Achieving the government's target of a maximum wait of 13 weeks for a first outpatient appointment requires a greater appreciation of randomness in the GP referral rate and non-attendance rate. It is possible to analyse what effect randomness will have on waiting times. The number of GP referrals received in December is a critical factor in determining end-of-year performance in meeting the 13-week target. PMID- 11216236 TI - Treating acute pain in addicted patients. PMID- 11216237 TI - Assessing thyroid function with serum tests. PMID- 11216239 TI - Reviewing the nervous system. PMID- 11216238 TI - Safeguarding contrast media injections. PMID- 11216240 TI - Take a look at ginseng. PMID- 11216241 TI - What you should know about managing burn emergencies. PMID- 11216242 TI - Action stat. Neuroleptic malignant syndrome. PMID- 11216243 TI - Is professional liability insurance for you? Before you say no, weigh these considerations. PMID- 11216244 TI - Expanded ECGs: easy as V4, V5, V6. Use these techniques to get a wider view of myocardial damage. PMID- 11216245 TI - What the future holds for gerontology. PMID- 11216246 TI - New drugs 2001. Part I. PMID- 11216247 TI - The child left behind. PMID- 11216248 TI - Managing a pressure ulcer. PMID- 11216249 TI - Applying a condom catheter. PMID- 11216250 TI - Chlamydia trachomatis. PMID- 11216251 TI - Myths & facts ... about kidney stones. PMID- 11216252 TI - What's "professional" work? PMID- 11216253 TI - Actions speak louder than words. PMID- 11216254 TI - "Don't forget me". PMID- 11216255 TI - Breast feeding. PMID- 11216256 TI - Midwives in Victoria, Australia: a survey of current issues and job satisfaction. AB - OBJECTIVE: To describe demographic and work profiles of registered practising midwives, to assess their job satisfaction and their knowledge of and attitudes to the 1990 Victorian Birthing Services review. DESIGN: A questionnaire posted in 1995 to a population-based random sample of registered midwives. PARTICIPANTS: Two hundred and forty midwives currently using their midwifery skills in their work. SETTING: One thousand names and addresses were randomly selected from a database of midwives registered to practise in Victoria, Australia in 1993. FINDINGS: There was a 72% response rate to the postal questionnaire. Two hundred and forty practising midwives returned completed questionnaires. Seventy-three per cent were in full time employment, 49% lived in rural Victoria, 80% were born in Australia, more than half were aged 40 or more years and 72% had at least one child. Twenty-six per cent worked in postnatal wards, 9% in each the labour ward and the neonatal nursery, 2% in birthing centres and 12% in out of hospital settings. Eighty per cent were satisfied with their work and interactions with women were the most important aspect. Satisfaction was associated with working in a labour ward, feeling adequately prepared by midwifery education and training, nursing for more than 15 years and having continuing education. Neonatal and rotating positions were significantly associated with dissatisfaction. Less than one-half of the midwives had read some of the Birthing Services Review, and of these only one-half had changed their attitudes or practice. One-third knew little of the imminent changes to the Midwifery Regulations. CONCLUSION: Although most midwives enjoyed their work there was little evidence of increasing autonomy or involvement in change. PMID- 11216257 TI - Falling by the wayside: a phenomenological exploration of perceived breast-milk inadequacy in lactating women. AB - OBJECTIVE: To provide insight into the lived experience of breast feeding, in primiparous women. The main focus was upon women's perceptions related to the adequacy of their breast milk, for the purpose of exclusively nourishing their babies. DESIGN: A longitudinal, phenomenological study involving in-depth, interactive interviews, conducted at 6, 12 and 18 weeks following the birth of the women's babies. PARTICIPANTS AND SETTING: A convenience sample of ten primiparous women were recruited prior to discharge from a maternity unit, in the north of England, in 1998. FINDINGS: Two groups of participants emerged, three who became increasingly confident and empowered by breast feeding and the remaining seven whose confidence progressively diminished, with six of them expressing concern that their breast milk was inadequate. Four major themes related to the participants' perceptions emerged from the analysis: the quest to quantify and visualise breast milk; anxiety regarding the adequacy of their diet; breast feeding as a challenging journey, with most feeling that they had 'fallen by the wayside' (this related partly to inadequate and conflicting advice given by health professionals); and finally, unmet needs for support, nurturing and replenishment in return for 'giving out'. CONCLUSION: Perceived breast-milk inadequacy is underpinned by a complex and synergistic interaction between socio cultural influences, feeding management, the baby's behaviour, lactation physiology and the woman's psychological state. IMPLICATIONS: Education of midwives and health visitors is required in relation to the needs of breast feeding mothers within a Western industrialised society. Strong social policy is vital in the UK, to initiate socio-cultural changes, which would enable women who commence breast feeding to perceive it as an empowering and fulfilling experience and not one of 'falling by the wayside'. PMID- 11216258 TI - A feminist analysis of women's experiences of perineal trauma in the immediate post-delivery period. AB - OBJECTIVE: To provide an account of women's experiences of perineal trauma in the immediate post-delivery period. DESIGN: Qualitative, using unstructured interviews with broad questions about experiences of childbirth and perineal trauma. SETTING: The South Wales. PARTICIPANTS: A snowball technique was employed to recruit six participants, all of whom were between 25 and 40 years of age, white, British and had had access to further education. FINDINGS: The women identified several factors which informed their experience. Of significance to midwives are the following: the doctor--'patient' relationship, particularly in relation to gender, not feeling heard, the expression of feelings; and a lack of available information and advice. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The study identified some of the reasons why women sufferers find it difficult to get these issues on the health-care agendae and the need for more research. Improvements in care are necessary in the areas of interpersonal skills and perineal suturing. Listening to women is the key to responsive care. PMID- 11216259 TI - To see or not to see? Midwives' perceptions of reduced antenatal attendances for 'low-risk' women. AB - OBJECTIVE: To explore the views of midwives towards traditional and flexible schedules of antenatal attendance for women at low risk. DESIGN: A qualitative approach using focus groups. SETTING: Three NHS Trusts providing maternity care in and around Bristol. SAMPLE: 14 midwives who had provided antenatal care to women participating in the Bristol Antenatal Care Study. FINDINGS: Midwives generally expressed support for a move away from the traditional schedule of antenatal attendances, suggesting that this represented a move towards the acceptance of pregnancy as a normal life event. They recognised that some women would prefer flexible care and the possibility of a reduction in the number of antenatal attendances. However, they suggested that some women would require additional information in order to feel confident in these circumstances. The midwives also recognised that both they and pregnant women have reservations about reducing contact during the antenatal period. Central to these reservations is a concern that women's psychosocial as well as physical needs may go unmet if antenatal contact is reduced. IMPLICATIONS FOR PRACTICE: Although in principle supporting a move away from the traditional schedule of antenatal attendances, the reservations felt by midwives towards a reduction in antenatal attendances are reflected in their practice. These concerns currently impede any radical move away from the traditional schedule of antenatal check-ups and will need to be addressed by midwifery managers prior to the implementation of a more flexible schedule of antenatal attendances, if any such change is to be sustainable. PMID- 11216260 TI - Student midwives' views of 'learning to be a midwife' in Ireland. AB - OBJECTIVE: To explore the opinions, feelings and views of student midwives of their education as they progressed through their two-year programme in Ireland, with the intention of interpreting and understanding the working and learning world of the participants so that future students might be assisted to improve their educational experiences. DESIGN: Quantitative and qualitative methods. A phenomenological approach was used to guide the qualitative section of the study. SETTING: All seven midwifery schools in Southern Ireland. PARTICIPANTS: All students in the first intake of 1995 in every midwifery school in Ireland (n = 125). DATA COLLECTION: Individual and group interviews, diary-keeping and questionnaires. KEY CONCLUSIONS: The findings presented in this paper illustrate the students' views of their education. Students perceived themselves as part of the workforce and believed that their educational needs were denied. They were given little clinical teaching and guidance and were not assisted to learn the skills of decision-making or judgement. Much of their learning took place by trial and error. The 13 weeks allocated for theoretical input in the midwifery education programme in Southern Ireland is far too short and many students thought that time was wasted. Relationships with the teaching staff were good, although some authoritarian attitudes were evident and teaching did not appear to be student-focused. IMPLICATIONS FOR PRACTICE: Theoretical teaching needs to be broadened and thought given to the integration of theory and practice. Clinical teaching is a necessity throughout the two-year programme and opportunities to teach while giving care should be identified and utilised. The use of prepared mentors, sufficient support staff and longer allocations to each area are recommended. PMID- 11216261 TI - A comparison of two methods of antenatal breast-feeding education. AB - OBJECTIVE: To compare a woman-centered antenatal breast-feeding programme based on concepts of peer and husband/partner support with a control group, who received antenatal breast-feeding education led by a midwife childbirth educator. DESIGN: Longitudinal, quasi-experimental study. SETTING: A large private hospital in Sydney. PARTICIPANTS: A convenience sample of 179 primiparous women who attended childbirth education classes were recruited. One hundred and fifty-four participants remained following attrition and the application of selection criteria. There were 86 participants in the control group and 68 in the experimental group. The study population had a mean age of 30.4 years, were all married or living with a partner, were predominantly Australian born citizens (84%), and recorded a higher than average level of education than the population in general (Australian Bureau of Statistics 1997). INTERVENTION: Nursing Mothers Association Australia (NMAA) representatives, their male partners and a mother who was willing to demonstrate breast-feeding, facilitated the experimental group. MEASUREMENTS AND FINDINGS: Maternal perceptions of success using the Maternal Breastfeeding Evaluation Scale (MBFES) (Leff et al. 1994) and breast feeding duration rates up to 25 weeks after birth were the outcome measures. No differences were found between groups in relation to maternal perceptions of success or duration rates. A difference was, however, detected in the qualitative data used to explore questions related to breast-feeding support and are to be reported elsewhere. Overall, breast-feeding duration rates were very high when compared to previously reported breast-feeding duration rates in Australia. There were no differences in breast-feeding duration rates or in maternal perceptions of success between those babies given supplementary feeds in hospital and those who were not, although early supplementation at home appeared to reduce breast feeding duration. IMPLICATIONS FOR PRACTICE: While no differences were found between groups in relation to breast-feeding duration and maternal perceptions of success, the homogeneity of the sample limits its extrapolation. The extraordinary rates of breast-feeding and the lack of research into antenatal breast-feeding education, warrants further investigation of these teaching styles across other populations. Importantly, this research found that a peer-led model of breast-feeding education was as effective as a midwife-led group in producing breast-feeding initiation and duration rates higher than other previously reported breast-feeding rates with the potential to enhance social support networks. PMID- 11216262 TI - Aspects of the preparation of student midwives for autonomous practice. AB - OBJECTIVE: To investigate aspects of the preparation of student midwives for autonomous practice, within the context of the relationship between the student and her supervising midwife. DESIGN: A qualitative research design was used and responses from in-depth interviews were analysed utilising the principles of grounded theory. SETTING: Interactions between the student and supervising midwife in the clinical setting were used to explore preparation for autonomous practice including issues in socialisation, role of the midwife, variations in placements and practice. SUBJECTS: Seven student midwives and their seven identified midwife 'supporters' and four midwives working on night duty. Initially purposeful in nature, the sample developed towards a theoretical sample. FINDINGS: Analysis revealed nine related categories common to this relationship presented within the themes of Recognition, Incorporation and Facilitation. KEY CONCLUSIONS: The findings suggest that students exhibited a fear of independent action through non-assertive behaviour, passive learning and subsequent compliance. Students were observing role conflict as the midwives in the hospital environment aimed to provide women-centred care whilst juggling with the restrictions on their practice, a situation which may be accepted or, at times, challenged by the student. IMPLICATIONS FOR PRACTICE: Midwives need to be aware of factors which influence their ability to be autonomous practitioners and how this relates to educational preparation in midwifery. PMID- 11216263 TI - [Electroconvulsive therapy: indications and contraindications. Nursing care]. PMID- 11216264 TI - Water birth: a safe practice? PMID- 11216265 TI - Nurse prescribing: understanding generic medicines. PMID- 11216266 TI - Recent advances in natural family planning. PMID- 11216267 TI - Postnatal depression: involving partners in promoting recovery. PMID- 11216268 TI - Children's feet: common worries of parents--2. PMID- 11216269 TI - A busman's holiday with PEAK. PMID- 11216270 TI - Menstruation in schoolgirls--2: Early and late puberty. PMID- 11216271 TI - Educating patients and families about solid organ transplantation. PMID- 11216272 TI - Use of arginine vasopressin in the absence of diabetes insipidus: a case study. AB - This case study details the use of arginine vasopressin in a pediatric organ donor. Although arginine vasopressin is primarily administered for its antidiuretic effects in the treatment of diabetes insipidus, the study demonstrates the often overlooked vasoactive effect of arginine vasopressin and its use in a patient without diabetes insipidus. PMID- 11216273 TI - Regulation of coagulation abnormalities and temperature in organ donors. AB - The 3 most common reasons for abnormal coagulation of blood in organ donors result from prior medications, consumption or dilution of coagulation factors and platelets during massive transfusion, and disseminated intravascular coagulation. Evaluation and treatment of these conditions are reviewed, and recommendations are provided for ordering appropriate laboratory tests and blood bank products. PMID- 11216274 TI - Overcoming families' fears and concerns in the donation discussion. AB - Research into the fears and concerns families have about donation and other issues at the time of the donation discussion substantiates that many fears and concerns act as impediments to consent. Twenty fears and concerns voiced by families at the time of the donation discussion have been identified. Specific strategies have been developed to deal with 19 of those concerns. Using gentle probing questions and targeted strategies, trained requestors may successfully address many fears and concerns, thus increasing the likelihood of the family consenting to donation. PMID- 11216275 TI - Clinical risk associated with appointment noncompliance in heart transplant recipients. AB - This study examined the prevalence of appointment noncompliance in 101 heart transplant recipients and how appointment noncompliance is related to patient profile and clinical risk. Appointment noncompliance was defined as patients not showing up at 1 or more planned clinic appointments (at a minimal frequency of every 3 months) during the previous year. Clinical variables were collected from medical files. Psychosocial variables were measured using established instruments. Medication noncompliance was assessed using electronic event monitoring. Paired t test, Wilcoxon 2-sample test, chi-square test, or Fisher exact test were used for statistical analysis as appropriate. The prevalence of appointment noncompliance was 7%. Appointment noncompliers were significantly younger, were less likely to live in a stable relationship with a partner, were more depressed, perceived their health as poorer, experienced more symptom distress, and had significantly more drug holidays. Fifty-seven percent of the appointment noncompliers experienced 1 or more late acute rejection episodes, compared to 2% of the appointment compliers. Appointment noncompliance is a critical behavioral risk factor in the occurrence of late acute rejection episodes in heart transplant patients. Patient profiles allow the identification of patients at risk for appointment noncompliance. PMID- 11216276 TI - Teaching patients about kidney transplantation: documentation. AB - Increasing demands are being placed on transplant nurse coordinators for more precise documentation of their teaching of kidney transplant patients, but the amount of time nurses have for this added documentation remains unchanged or has diminished. After a thorough review of the literature, our transplant team found no patient teaching documentation format that assisted us in overcoming the problem of increased demands. Consequently, following the Joint Commission on Accreditation of Healthcare Organization standards, we developed a Renal Transplant Patient Teaching Record that has assisted our team in documenting the pre- and post-transplant patient teaching that we complete. PMID- 11216277 TI - Hostility toward caregivers as a selection criterion for transplantation. AB - Researchers have focused on hostility and aggression of psychiatric patients but little is known about what effects transplant candidates' hostility toward their caregivers has on the care the candidates receive. Hostility is defined as any verbal, nonverbal, or physical behavior which threatens persons or property. Although hostility may be one of the precipitating factors in the need for an organ transplant, it may also be a response of the patient to his or her condition. This study focused on whether transplant coordinators felt that hostility should be used as a criterion for accepting or rejecting a transplant candidate. A nonexperimental descriptive survey design targeted 559 organ transplant coordinators who were members of the North American Transplant Coordinators Organization. Many coordinators in this study (62%) felt that a hostile candidate should not receive an organ transplant. Different methods of caring for hostile patients should be explored, especially for those who are antagonistic and who exhibit aggressive behaviors. Given the scarcity of donor organs, ethical principles must guide the allocation of these organs and the selection of transplant recipients. PMID- 11216279 TI - Giving carers a choice and a voice. PMID- 11216278 TI - Reliability of ultrasound screening of liver and kidney donors: a retrospective study. AB - The reliability of abdominal ultrasound in screening liver and kidney donors was assessed by correlating ultrasound findings with the suitability of organs for transplantation as determined by direct examination of the organs. We evaluated 100 multiorgan donors (100 livers, 200 kidneys) during a 15-month period. Abdominal ultrasound showed the following results for liver and kidney, respectively: specificity, 95.6% and 98.9%; sensitivity, 62.5% and 66.6%; and accuracy, 93% and 97%. These results show that abdominal ultrasound is a valuable tool for determining suitability of organs for transplantation when the ultrasound findings are normal. When ultrasound findings are abnormal, further studies are necessary to determine the suitability of the organs for transplantation. PMID- 11216280 TI - Audit of emergency detention. PMID- 11216281 TI - Pressure sore prevention in nursing homes. AB - Staff working in nursing homes are caring for ever more dependent residents who are consequently at great risk of developing pressure sores. Mary Clay offers a guide to the essential principles as a teaching aid for all caring staff. PMID- 11216282 TI - We are people, not diseases. PMID- 11216283 TI - A learning organisation. PMID- 11216284 TI - Changes to the RCN membership structure. PMID- 11216286 TI - Assessment of incontinence. PMID- 11216285 TI - A patient's view. PMID- 11216287 TI - Life across three centuries. PMID- 11216288 TI - New guideline represents 'processed-oriented' approach for ISO 9000. AB - Hospitals that have been tracking the development of ISO 9000 in the health care industry should pay close attention to a new guideline about to emerge. According to Laura Preole, health care services manager of SGS International Certification Services based in Rutherford, NJ, the new guideline is the latest step in an effort to establish a more 'process-oriented' method of looking at the health care environment from the moment a patient walks into a facility to the moment he or she is discharged. PMID- 11216289 TI - Final privacy rules create more questions. AB - Buried in the final patient privacy regulations released by the Clinton administration are a host of changes from the proposed regulations that will directly affect quality assurance managers, according to experts who have been sifting through the 1,500-page document since it was released Dec. 21. PMID- 11216290 TI - HHS database is risky source for credentialing. AB - Hospitals are running a considerable risk if they rely too heavily on the National Practitioner Data Bank (NPDB) as a source of information throughout their credentialing process. A report released recently by the General Accounting Office, which found the data bank riddled with problems, only underlines that point. The government watchdog agency says problems of underreporting to the NPDB make it a questionable source of information regarding disciplinary actions taken against health care practitioners by hospitals and other health care providers. PMID- 11216291 TI - Use XmR (individual and moving range) charts to better understand performance. Part 2. PMID- 11216292 TI - JCAHO alert on infusion pumps raises concern. AB - The Joint Commission on Accreditation of Healthcare Organizations issued a Sentinel Event Alert Nov. 30 that says human and medical errors involving the use of infusion pumps have led to several deaths and near-fatal drug overdoses. But industry representatives fault the Joint Commission for failing to provide adequate guidance for ongoing assessment. PMID- 11216293 TI - Going super slow. Lifting weights at a snail's pace can work wonders. Is it the whole key to fitness? PMID- 11216294 TI - The efficacy of communicative fairness and rhetorical aesthetics in contributions to argumentation. AB - This paper deals with the effects of aesthetic quality and argumentational integrity or fairness on the persuasiveness of contributions to argumentation. Contemporary discussions of aesthetics and morality distinguish three possible relationships: (a) superiority of aesthetics in making contributions persuasive, (b) integrity as a necessary precondition for the efficacy of aesthetics, and (c) a compensatory relationship between aesthetics and integrity. Basic argumentative dialogs were varied in aesthetic quality via the use of figurative language and in fairness via the addition of faulty, insincere, or unjust arguments. Materials were presented in a written (Study I) or spoken form (Study II), and followed with questions exploring cognitive, emotional, and conative aspects of persuasive efficacy. Results of both studies strongly support case (b): Only in arguments perceived as fair can persuasive impact be enhanced by aesthetic means. PMID- 11216295 TI - Garden path repair: diagnosis and triage. AB - Meng and Bader (2000b) have shown that for garden-path repair in German, case is a more effective cue than number. They argue that sensitivity to the nature of the cue supports a diagnosis model of garden path repair such as we have proposed. However, in making this argument Meng and Bader introduced a new notion of diagnosis. Retaining the original "basic" diagnosis system, they added a new function that we call triage. Triage determines the probable revisability of a structure, in order to decide whether to make the effort of trying to reanalyze it. To determine whether triage is a feature of human parsing, its scope must be established. We compare four hypotheses about how much work triage could do. A powerful triage component would succeed where the human parser fails. Limited local triage does no work if symptom effectiveness varies within a language. An intermediate hypothesis discriminates better between easy and difficult revisions. However, this variant of triage with the strongest claim to psychological reality is the most difficult to distinguish from no triage at all, since it shares important properties with basic diagnosis. We identify some empirical predictions that differentiate diagnosis with triage from simple basic diagnosis. What little evidence there is at present suggests that the human sentence parser has no triage capability. PMID- 11216296 TI - The effect of cue-enhancement on consonant intelligibility in noise: speaker and listener effects. AB - Our previous work (Hazan & Simpson, 1998) has shown that increasing the salience of perceptually important regions of nonsense word and sentence materials aids speech perception in noise. This study aimed to extend these findings by investigating the robustness of these enhancement techniques in improving consonant intelligibility for a range of different speakers and for groups of listeners with different language backgrounds. In Experiment 1, nonsense vowel consonant-vowel (VCV) tokens produced by two female and two male speakers without phonetic training were annotated to highlight segments of the signal corresponding to the consonant constriction/occlusion and vowel onset/offset regions. These regions were selectively amplified to enhance the cues they contained, then combined with speech-shaped noise at 0 dB SNR and presented to normally hearing listeners. Significant improvements in intelligibility were found for all speakers although the extent of the improvement varied across speakers. In Experiment 2, a subset of these stimuli were presented to two groups of learners of English--a Japanese-L1 group and a Spanish-L1 group--and a new group of native-English controls. Results showed a significant effect of enhancement in all listener-groups and similar speaker effects for the non-native and native English listeners. Error patterns were related to the distance between the phonological systems of listeners' L1 and L2. PMID- 11216297 TI - The Hebrew vowel system: raw and normalized acoustic data. AB - It is well known that different languages use different vowel systems in terms of variety and number. The Hebrew vowel system consists of five vowels /i, e, a, o, u/. The present research identified the acoustic features of the vowels produced by Hebrew speakers differing in age and sex. Ninety speakers (men, women, boys, and girls) were recorded. The vowels were presented in a nonword context that was placed in a meaningful Hebrew sentence. The data included measurements of F0, F1, F2, F3, F4, and vowel duration for the five different vowels produced by the four groups of participants. Conversion of the physical frequency measures of formants into a critical band (bark) scale was performed as well. The results indicated that the F2/F1 ratio is a distinctive feature of all five vowels, keeping with the findings of previous research in other languages. Nevertheless, the values of the F2/F1 ratios led to an overlap between different vowels produced by different groups of speakers. Applying the bark transformation as speaker normalization procedure succeeded in reducing speaker differences while increasing vowel differences. PMID- 11216298 TI - Prosodic variation in southern British English. AB - A neglected aspect of intonation research has been the nature and extent of variability in the use of prosodic features within a speech community. Cross speaker variability in intonation was investigated through analysis of data collected from 90 adult speakers of English from London, England, using a new prosodic test battery (PEPS). PEPS is designed to elicit information about how speakers use prosodic features to realize different types of linguistic and communicative function in their own speech, and also how they perceive and interpret these features. Although there were no significant effects of gender or age in isolation on prosodic performance, there was a small effect of educational level among younger adults. Despite this group homogeneity, qualitative analysis of data from two of the production tasks showed considerable variation across participants in their use of prosodic features, suggesting that speakers' realization of communicative functions through prosody is more variable than has hitherto been assumed. PMID- 11216299 TI - Re-examination of the role of within-compound associations in the retrospective revaluation of causal judgements. AB - We investigated blocking and retrospective revaluation of causal judgements using a scenario in which food cues acted as potential causes of an allergic reaction as the outcome. In the blocking contingency, the treatment cues were either paired or unpaired with the outcome prior to a second stage in which sequential compounds of treatment and target cues were paired with the outcome. The order of this compound and treatment training was reversed in retrospective revaluation contingencies. When the interstimulus interval between the treatment and target cues was unfilled on compound trials (Experiments 1 and 3), both blocking and retrospective revaluation were observed in that the target cue trained in compound with the paired treatment cue attracted lower causal ratings than the target cue trained in compound with the unpaired treatment cue. By contrast, performing a mental arithmetic task using numerals presented during the interstimulus interval had no effect on the magnitude of blocking but rendered retrospective revaluation unreliable (Experiments 2 and 3). These results provide further support for accounts of revaluation based upon within-compound associations. PMID- 11216300 TI - The 28th Bartlett Memorial Lecture. Causal learning: an associative analysis. AB - The concordance between performance and judgements of the causal effectiveness of an instrumental action suggests that such actions are mediated by causal knowledge. Although causal learning exhibits many associative phenomena- blocking, inhibitory or preventative learning, and super-learning--judgements of the causal status of a cue can be changed retrospectively as a result of learning episodes that do not directly involve the cue. In order to explain retrospective revaluation, a modified associative theory is described in which the learning processes for retrieved cue representations are the opposite to those for presented cues, and this theory is evaluated by studies of the role of within compound associations in retrospective revaluation and blocking. However, this modified theory only applies when the within-compound association represents a contiguous rather than a causal cue relationship. PMID- 11216301 TI - Unequal associative changes when excitors and neutral stimuli are conditioned in compound. AB - In four experiments a compound of a previously conditioned excitor and a neutral stimulus was either reinforced with food or nonreinforced. Two experiments used a magazine approach procedure in rats, and two used an autoshaping procedure in pigeons. All experiments employed a novel compound test procedure, which permitted evaluation of the size of the associative change that took place for the excitatory and neutral stimuli. Reinforcement of the compound resulted in greater increments in the associative strength of the neutral stimulus than of the excitor. Nonreinforcement of the compound resulted in greater decrements in the associative strength of the excitor than of the neutral stimulus. These results agree with earlier experiments with compounds of excitors and inhibitors and provide an additional challenge to contemporary error-correction models of conditioning. PMID- 11216302 TI - A differential outcomes effect using biologically neutral outcomes in delayed matching-to-sample with pigeons. AB - The differential outcomes effect (DOE) pertains to enhanced conditional discrimination performance if each correct stimulus-choice sequence is always followed by a different outcome (e.g., food vs. water) compared to when each correct sequence is followed equally often by either outcome. The present experiments sought evidence of a DOE in pigeons, using biologically neutral outcomes. Experiment 1 replicated findings with rats demonstrating that a DOE can occur when one outcome is a biologically neutral light and the other is the absence of that light. Experiment 2 extended these findings by demonstrating a DOE when two biologically neutral outcomes of similar sensory and associative properties were employed. PMID- 11216303 TI - Guidelines for psychologists working with animals. PMID- 11216304 TI - Should antibiotics now be part of routine treatment of coronary heart disease? PMID- 11216305 TI - Malaria, mefloquine and oil-workers. PMID- 11216306 TI - Munchausen files in Scottish A&E Departments: a review of current practice. AB - Our objective was to describe current use of Munchausen files in Scottish Accident and Emergency Departments. A Postal questionnaire survey was sent to lead A&E consultant/clinical directors in each department in Summer 1998. A total of 29 departments replied with 27 saying they kept a Munchausen file, of which only two were updated regularly. Organisation of information was variable or absent. Six departments kept data on other groups such as drug misusers, violent patients, missing persons or children at risk in the same file. Of the 27 replies, only 14 departments would review their own files if suspecting a case; only 11 would report a suspected incident, to a variety of destinations. The majority of Scottish A&E departments do keep a Munchausen file although there appears to be little consistency in the collection, use and dissemination of the information therein. An improved data system may lead to more appropriate patient management. PMID- 11216307 TI - Lithium therapy. AB - Affective (mood) disorders are common in all ages often chronic or recurrent, destructive of personal and social functioning with significant morbidity and mortality. Diagnosis still rests on the clinical skills of interview, observation and a knowledge of the disorders. Lithium is simple, cheap and effective although underused. It is the main pharmacological agent currently used in bipolar disorders and as an adjunct in other affective disorders. While it does have a narrow therapeutic window and can cause serious morbidity itself, it is safe when delivered properly reducing both morbidity and mortality. Lithium therapy should only be started in a specialist psychiatric setting but other clinicians will be involved either in maintenance treatment or in treating patients for separate disorders who happen also to be on lithium. PMID- 11216308 TI - An evaluation of a primary care psychological therapies clinic. AB - The present study evaluates a primary care psychological therapies clinic providing input one day per week to a GP practice in a rural area of Scotland. Routine data was collected over a 17 month period and a rating scale was used to evaluate treatment outcomes by both GPs and therapist. In addition GP satisfaction with the service was also evaluated. No significant differences were found between counselling and psychology cases on any of the variables examined. Treatment outcome evaluation showed an overall rate of improvement following treatment, with a mean score of 7 on a 1-10 scale, with 10 representing 'much better'. Significant agreement was found between therapist and GP on rating outcome and no significant differences were found between ratings given by psychologist and counsellor. The GPs involved also expressed high levels of satisfaction with the service. PMID- 11216309 TI - Trilucent breast implants--a personal review of the current controversies (May 1999). AB - Trilucent ("Soya Bean") breast implants were marketed as a safe alternative to silicon implants. Following their use in the UK for the past four years, a reassessment of this has currently been announced (March 1999) and further implantation has been suspended by the Trilucent company in conjunction with the MDA (Medical Devices Agency). This has been the result of some reports of adverse reactions to the triglyceride filling material when the implant ruptures. All patients with trilucent implants were advised to return to their respective surgeons for review and advice. A personal review has been undertaken by the author of this paper. The results obtained are discussed. The majority of patients were concerned, but were happy with cosmetic results, and did not at present wish their implants removed. None appeared as yet to have had serious complications that could be attributed to the implants. PMID- 11216310 TI - Management of myocardial infarction in the very elderly--impact of clinical effectiveness on practice. AB - The presentation of myocardial infarction in the elderly is often atypical and there is therefore a broad range of clinical presentations where this diagnosis should be actively considered and the appropriate investigations arranged. The early use of aspirin and thrombolytic therapy has revolutionised management and efforts should be made to employ these interventions wherever possible. We present the results of an audit showing how the introduction of local guidelines improved the early management of myocardial infarction in the elderly. We also found that in this group of patients cardiac enzyme assays were more useful in establishing the diagnosis than the electrocardiogram. PMID- 11216311 TI - Tuberculosis revisited or how we nearly conquered tuberculosis. AB - This article recounts the author's experience as a chest physician in the years after the Second World War when Scotland experienced a serious epidemic of tuberculosis. With the discovery of streptomycin, PAS and isoniazid this disease became for the first time eminently treatable, and the team in Edinburgh demonstrated how the routine use of these three drugs in all cases ensured that the patient progressed to cure with virtually no cases of drug resistance. This policy, although fully supported by follow-up studies, was only very slowly adopted elsewhere, and since that time there have been numerous errors and difficulties in treatment regimens in many parts of the world. The result is that a great therapeutic opportunity has been lost and the Worldwide situation is worse than ever, mainly due to increased incidence of TB in the countries of the Third World. PMID- 11216312 TI - Dissociable lexical and phonological influences on serial recognition and serial recall. AB - The impact of the lexicality of memory items on memory performance was compared in two paradigms, serial recall and serial recognition. Experiments 1 to 3 tested 7- and 8-year-old children. Memory accuracy was only mildly impaired in lists containing nonwords compared with words in a serial recognition task involving judgments of whether the items in two sequences were in the same order (Experiment 1), although a substantial advantage for word over nonword items from the same stimulus pool was found in serial recall (Experiment 2). A stronger influence of lexicality on serial recall than serial recognition was further demonstrated in Experiments 3A and 3B, and in 4A and 4B using adult participants. These experiments also established comparable degrees of sensitivity to the phonological similarity of the memory sequences in the two paradigms. The phonological similarity effect in serial recall was found to arise from increased phoneme order errors, whereas the lexicality effect was due principally to the greater frequency of phoneme identity errors for nonwords. It is proposed that the lexicality effect originates in the redintegration of item information just prior to recall, and that this process is largely bypassed in serial recognition. PMID- 11216313 TI - Can actions affect perceptual processing? AB - Previous studies reported impairments in a perceptual task performed during the selection and execution of an action. These findings, however, always raise the question of whether the impairment actually reflects a reduction in perceptual sensitivity or whether it results only from an unspecific reduction in attentiveness given the perceptual task. Recent studies by the authors indicate that actions can also have a specific impact on perception in a dual-task situation. The identification of a left or right arrow is impaired when it appears during the execution of a compatible left or right keypress. In three experiments Signal Detection Theory is applied to test whether this impairment is also found in the sensitivity measure d' or whether it originates only from a response tendency. The results revealed a general lower d' for the identification of arrows that were compatible to simultaneously executed keypresses than for arrows that were incompatible. The bias measure c was small and/or did not differ between conditions. Additional analyses revealed that the impairment is due to a higher mean perceptual degradation of stimuli in the compatible condition and that it is restricted to the point in time when the central movement command is generated. Thus, actions actually seem able to affect perceptual processing. PMID- 11216314 TI - Location and attention. AB - A discrepancy exists in the literature concerning attention and visual localization accuracy. Prinzmetal, Amiri, Allen, and Edwards (1998), and Tsal and Bareket (1999a) found that localization accuracy increases with attention. Using an inattention paradigm, Rock, Linnett, Grant, and Mack (1992) found no difference between localization accuracy in three attention conditions: inattention, divided attention, and control. Using a similar inattention paradigm, the current study addressed this discrepancy. Subjects were instructed to perform a line judgement task, and attention for an additional location task was manipulated. In Experiment 1, location accuracy was worse in the inattention condition than in either the divided-attention or the control condition. There was no difference between the divided-attention and control conditions. Experiment 2 controlled for the possibility that improved location accuracy in the divided and control conditions was due to the expectation of performing a location response, rather than the manipulation of attention. Our results are in agreement with previous findings (Prinzmetal et al., 1998; Tsal & Bareket, 1999a) and suggest that the apparent discrepancy is due to coarse coding of the location responses in the study by Rock et al. (1992). PMID- 11216315 TI - The attentional blink is immune to masking-induced data limits. AB - The attentional blink is the robust finding that processing a masked item (T1) hinders the subsequent identification of a backwards masked second item (T2), which follows soon after the first one. There has been some debate about the theoretically important relation between the difficulty of T1 processing and the ensuing blink. In Experiment 1 we manipulated the difficulty of T1 in such a way as to affect the quality of data without altering the amount of resources allocated to its identification. We found no relation between the accuracy of T1 identification and the blink. In Experiment 2, the same difficulty manipulation was applied to T2, and we observed an additive pattern with the blink. Together, this pattern of results indicates that a data-limited difficulty manipulation does not affect the blink, whether applied to T1 or T2. In Experiment 3 we used an individual differences methodology to show that performance in the traditional "stream"-like presentation (rapid serial visual presentation) was highly correlated with performance in our modified "target mask, target mask" paradigm, thus allowing for comparisons beyond the present methodology to much of the previous literature that has used the stream paradigm. PMID- 11216317 TI - Accessing source information in analogical problem-solving. AB - Several studies showed that people presented with source information fail to apply it to an analogous target problem unless they are instructed to use the source. Seven experiments were carried out to assess whether such a lack of spontaneous transfer occurs because individuals do not activate the source during the target task or because they do not realize the source-target relationship. Experiment 1 compared a condition in which the source was activated with no cue about the source-target connection to conditions in which subjects were informed about this connection. Results suggested that the lack of spontaneous transfer does not depend on failure in activating source information. Experiments 2, 3, and 4 were devised to falsify this finding by activating the source closer and closer to the target and by focusing participants' attention toward the relevant aspects of the source. Experiments 5, 6, and 7 were aimed at stressing source target correspondences by introducing surface similarities. All experiments showed that the mere activation of the source does not facilitate analogical transfer. Results suggested that two processes should be distinguished in the access phase of analogical problem-solving: Source retrieval and identification of the source-target connection. PMID- 11216316 TI - Central tendencies, extreme points, and prototype enhancement effects in ill defined perceptual categorization. AB - In three perceptual classification experiments involving ill-defined category structures, extreme prototype enhancement effects were observed in which prototypes were classified more accurately than other category instances. Such empirical findings can prove theoretically challenging to exemplar-based models of categorization if prototypes are psychological central tendencies of category instances. We found instead that category prototypes were sometimes better characterized as psychological extreme points relative to contrast categories. Extending a classic and widely cited study (Posner & Keele, 1968), participants learned categories created from distortions of dot patterns arranged in familiar shapes. Participants then made pairwise similarity judgments of the patterns. Multidimensional scaling (MDS) analyses of the similarity data revealed the prototypes to be psychological extreme points, not central tendencies. Evidence for extreme point representations was also found for novel prototype patterns displaying a symmetry structure and for prototypes of grid patterns used in recent studies by McLaren and colleagues (McLaren, Bennet, Guttman-Nahir, Kim, & Mackintosh, 1995). When used in combination with the derived MDS solutions, an exemplar-based model of categorization, the Generalized Context Model (Nosofsky, 1986), provided good fits to the observed categorization data in all three experiments. PMID- 11216318 TI - Hypothesis testing in a rule discovery problem: when a focused procedure is effective. AB - We investigated individuals' ability to use negative evidence in hypothesis testing. We compared performance in two versions of Wason's (1960) rule discovery problem. In the original version, a triple of numbers--(2, 4, 6)--was presented as an example of a rule that the experimenter had in mind (i.e., "increasing numbers"). Participants had to discover the rule by proposing new triples. In the other version, the same triple was presented as a counter-example to the experimenter's rule (i.e., "decreasing numbers"). We predicted that, in both conditions, participants would form hypotheses based on the features of the triple, and test only instances of the hypothesized rule. However, in the counter example condition, such focused testing would invariably produce negative evidence. As a consequence, participants would be forced to revise their hypotheses. The reported results corroborated our predictions: Participants solved the counter-example version significantly better than the original problem. PMID- 11216319 TI - Collecting information: optimizing outcomes, screening options, or facilitating discrimination? AB - Collection of information prior to a decision may be integrated into a compensatory choice process; if it is, the information packet that is collected should be the one that produces the highest net gain. Alternatively, information may be collected in order to screen out options that fail to meet minimum standards; if this is the case, people should not choose options on which they have not collected available information. We tested these and other predictions from the two approaches in four experiments. Participants were given specific information about three attributes of each choice option but only probabilistic information about a fourth one. They rated attractiveness of options, decided whether to collect specific information about the fourth attribute of each one, rated options again, and then selected one of them. Data were consistent with neither of the above approaches. Instead they suggested that people collect information in order to facilitate their ability to discriminate between the attractiveness of options. PMID- 11216320 TI - Processing and storage in working memory span. AB - Two experiments are reported that address theoretical assumptions as to the nature of working memory involved in working memory span tasks (Daneman & Carpenter, 1980). Experiment 1 used a version of the sentence span task, and Experiment 2 combined arithmetic verification with recall of presented words. In each experiment, working memory processing span was assessed independently of temporary storage span prior to their combination. Combined task performance under high demand for each component resulted in substantial residual performance for both task elements, particularly in Experiment 2. The results do not challenge the utility of the sentence span task as a measure of on-line cognition, but they raise concerns as to how resource might be allocated to processing and storage elements of the task within a single flexible resource pool, or between different resources of a multiple component working memory system. Although both models lack predictive power regarding resource allocation in these tasks, the multiple resource model appears to offer the better account. PMID- 11216321 TI - Memory discrimination for self-performed and imagined acts: bizarreness effects in false recognition. AB - Two experiments investigated the susceptibility of common and unusual action events to memory distortion under incidental learning and delayed testing conditions. Experiment 1 tested the influence of imaginal and enactment instructions at testing on memory discrimination for self-performed and imagined acts. The influence of hypnotic procedures at testing on memory discrimination for action events was tested in Experiment 2. The results of both experiments suggest that the likelihood of confusing details associated with separate, previously experienced unusual action events is greater than the likelihood of confusing details associated with separate, previously experienced common action events. Based on the results of both experiments, it is concluded that bizarreness has both memory-facilitating and memory-inhibiting qualities. PMID- 11216322 TI - Information and action in punching a falling ball. AB - Lee, Young, Reddish, Lough, and Clayton (1983) reported that the timing control of jumping and vertically punching a dropping ball exploits the inverse of the rate of change of optical expansion, tau(r). We raise a number of methodological and logical criticisms against their experiment and conclusions and attempt to rectify them by examining elbow joint angles only, in seated punchers, under both monocular and binocular conditions, with two ball sizes, dropped from two heights. Differences between the binocular and monocular cases suggest the exploitation of different information. We present several techniques to help determine the operative variable(s) controlling the action. The optical variable used to initiate and guide flexion appeared to be expansion velocity (looming), rather than tau(r); extension appeared to be under the control of different variables in the monocular and binocular cases. Simulations using single variables and single perceptuo-motor intervals were of mixed success. PMID- 11216323 TI - Influence of irrelevant information on human performance: effects of S-R association strength and relative timing. AB - Six experiments examined effects of stimulus-response (S-R) association strength and relative timing on the magnitude of consistency effects for irrelevant information in Stroop-like tasks. Keypresses were made to two-dimensional stimuli (a colour or location word surrounded by a coloured rectangle or arrow), with the irrelevant information presented simultaneously with or prior to the relevant information. With simultaneous presentation, irrelevant information affected performance regardless of whether its S-R association was weak or strong, if the relevant S-R association was weak (e.g., colour word to keypress). However, a weak irrelevant S-R association (location word to keypress) had little effect when paired with a strong relevant S-R association (arrow direction to keypress), except when the stimulus onset asynchrony (SOA) between the irrelevant and relevant information was 300 ms. When the relevant information was colour, the effect of an irrelevant colour word persisted at a 500-ms SOA but that of an irrelevant physical colour did not, reflecting different decay functions for irrelevant verbal and non-verbal information. The persisting effect of an irrelevant colour word was reduced by articulatory suppression and eliminated at extended SOAs of 3 s. The results indicate that whether the consistency effect patterns are symmetric or asymmetric is determined by the relative strengths of the relevant and irrelevant S-R associations, as specified by the criteria of conceptual and mode similarity. The magnitude of the consistency effect is also a function of the temporal overlap of the resulting response activation, which is determined primarily by mode similarity. PMID- 11216324 TI - Psychosocial dysfunction in tuberculosis patients. AB - Tuberculosis continues to be a major health problem in India. It carries social stigma and results in adverse psychological sequelae. In the present study, 50 patients suffering from tuberculosis were examined. There was higher degree of neuroticism and the patients with tuberculosis showed marked to severe psychosocial dysfunctioning in personal, familial, vocational, social and cognitive areas. PMID- 11216325 TI - Genetic analysis of fragile X-syndrome. AB - Fragile X-syndrome is the most common inherited cause of mental retardation. The key clinical features of the fragile X-syndrome in males are mental retardation, a long face with large everted ears and large testes. The disorder is associated with a visible fragile site at Xq27.3 at FMR-1 loucs with the amplification of (CGC) n repeat sequence. The early diagnosis of affected individuals are carriers who are not aware of their high risk of having an affected child is important for proper management and counselling. PMID- 11216326 TI - Critical issues in determining citizen's right to health care in India. PMID- 11216327 TI - Malignant potential of oral submucous fibrosis due to intraoral trauma. AB - It is not very clear why oral submucous fibrosis (OSF) is prone to develop squamous cell carcinoma (SCC). Experimental studies on hamster have shown that wounding of oral mucosa promotes induction of epithelial dysplasia (ED) initiated with carcinogens. Hence, a study was undertaken to find the effect of intraoral traumatic factors (ITF) in OSF. Randomly selected 110 OSF patients were divided into 2 groups: Traumatic group (TG), having tooth/malposed impacted third molar/appliance/calculus; and Non-traumatic group (NTG). Clinico-pathological features of traumatic mucosa of TG were compared with non-traumatized mucosa of NTG. It was found that amongst 60 TG cases there were 8 cases of SCC, 4 cases of leukoplakia and 1 case of lichenoid dysplasia and erythema, erosion and ulcer were mostly observed with sharp tooth (28) cases and malposed impacted tooth (19) cases. Further, various degrees of ED were seen in more cases of TG (23%) than in NTG (8%). This study concludes that traumatised mucosa in OSF due to various ITF may concentrate the carcinogens which by penetrating cause carcinogenesis of susceptible cells. PMID- 11216328 TI - Bacteriological study on pulmonary & extra-pulmonary cases of tuberculosis from central India. PMID- 11216329 TI - Post MTP haematometra--simulating ectopic pregnancy case report. PMID- 11216330 TI - Professional advice and readiness to change behavioral risk factors among members of a managed care organization. AB - OBJECTIVE: To ascertain factors related to readiness to change behavioral risk factors in members of a managed care organization (MCO). STUDY DESIGN: Cross sectional study. PATIENTS AND METHODS: A telephone survey reached 4667 (73%) of 6409 adult members of a Minnesota MCO attending 2 primary care clinics. Of these, 3826 members (82%) completed an interview designed to identify behavioral risk factors (smoking, consuming a high-fat diet, and physical inactivity) and readiness to change these behaviors. RESULTS: Among MCO members consuming a high fat diet, those most ready to change were older, were women, used more preventive services, and reported receiving professional advice about diet. For physical inactivity, those most ready to change were younger, women, and more educated; used more preventive services; and reported receiving professional advice about physical activity. Among smokers, those with higher readiness to change smoked fewer than 15 cigarettes a day, had higher self-efficacy, had no other smokers in the household, and reported receiving professional advice about smoking. After controlling for demographic variables and for use of preventive services, greater readiness to change for smoking (beta = 0.336, odds ratio [OR] = 1.40, P = .056), physical activity (beta = 0.651, OR = 1.92, P < .001), and diet (beta = 0.532, OR = 1.70, P < .001) was associated with having received professional advice to change these behaviors. CONCLUSIONS: Levels of readiness to change behaviors in MCO members who smoke, are inactive, or consume high-fat diets are similar to those reported in other populations. The association of professional advice to change behaviors with increased readiness to change for smoking, physical activity, and diet suggests that receiving professional advice on these topics might assist patients in changing adverse health-related behaviors. PMID- 11216331 TI - Comparison of cesarean section rates in fee-for-service versus managed care patients in the Ohio Medicaid population, 1992-1997. AB - OBJECTIVE: To examine changes over time in the cesarean section rates for fee-for service (FFS) beneficiaries versus enrollees of managed care programs (MCPs) in the Ohio Medicaid population. STUDY DESIGN: Cross-sectional study using linked Ohio birth certificates and Medicaid files. PATIENTS AND METHODS: Study patients were Medicaid-enrolled residents of urban counties who had singleton, live births from 1992 through 1997 (n = 86,459). Changes in primary and repeat cesarean section rates were analyzed in the FFS and MCP groups. The test of homogeneity of odds ratios was used to measure the statistical difference between unadjusted odds ratios. Logistic regression analysis was conducted to adjust for risk factors. RESULTS: From 1992 to 1997, the difference in the rates of primary and repeat cesarean sections between FFS and MCP patients decreased. The unadjusted odds ratio (OR) increased from 0.66 to 0.81 (P = .06) for primary cesarean sections and from 0.67 to 1.04 (P = .03) for repeat cesarean sections; this indicated that the likelihood of undergoing a cesarean section increased over time for MCP enrollees compared with FFS beneficiaries. The results of the multivariate analysis indicated that the interaction term of payment source by year was not significant for primary cesarean sections (adjusted OR = 0.93; 95% confidence interval = 0.83, 1.04), but was highly significant for repeat cesarean sections (adjusted OR = 0.53; 95% confidence interval = 0.44, 0.64). CONCLUSION: We observed a reduction in the difference between the rates of both primary and repeat cesarean sections in FFS and MCP patients over time. The reduction was not statistically significant for primary cesarean sections. For repeat cesarean sections, however, we observed a convergence of the rates for FFS and MCP patients. PMID- 11216332 TI - Predictive power of a risk-assessment questionnaire across different disease states: results in an elderly managed care enrolled population. AB - OBJECTIVE: To examine the predictive power of self-reported assessment questionnaire data to explain changes in healthcare service utilization and expenditures of a population of Medicare health maintenance organization enrollees during a 2-year period. STUDY DESIGN: A prospective cohort study with a 2-year postenrollment follow-up period. Multiple robust regression analyses were conducted to examine associations among self-reported health status variables obtained from responses to the questionnaire. SAMPLE AND METHODS: Participants were administered a voluntary comprehensive questionnaire at enrollment that collected self-reported information on morbidity, health status, perceptions of health, and healthcare service utilization during the preenrollment year. Questionnaire responses were combined with actual 2-year postenrollment claims data. For the complete follow-up period, 4128 patients were available. RESULTS: Participants with such chronic conditions as depression and diabetes were likelier than the average enrollee to have higher healthcare service utilization. Self-reported health status predictors examined in this study explained a larger percentage of the variance (as much as 20%) in such chronic conditions as cancer and depression. Despite evidence of underreporting of preenrollment healthcare service utilization, these variables were highly predictive of actual postenrollment utilization patterns. CONCLUSIONS: Self-reported health status information collected at baseline is as predictive of postenrollment risk as are currently used traditional approaches that require archival healthcare service utilization data. In addition, this approach is sensitive to changes in healthcare service utilization across differing morbidity states in older adults. PMID- 11216333 TI - A satisfaction and return-on-investment study of a nurse triage service. AB - OBJECTIVE: To assess patient satisfaction and a health plan's return on investment associated with a telephone-based triage service. STUDY DESIGN: A pre post study design, with medical claims data, to assess changes in medical service utilization and health plan expenditures associated with members' use of the triage service. PATIENTS AND METHODS: This study is based on data on 60,000 members of a health plan. A telephone survey was conducted to assess member satisfaction and outcomes with the triage service. The plan's medical claims and encounter data were used to calculate medical utilization rates and plan expenditures for those services. The health plan's return-on-investment was evaluated using a pre/post study design to assess changes in medical service utilization between the baseline (December 1995 through November 1996) and program (December 1996 through November 1997) periods. RESULTS: The average nurse response time to a call was just less than 50 seconds, which indicates the service provided ready access to medical advice 24 hours per day, 7 days per week. More than 90% of users were satisfied, and utilization of hospital emergency department (ED) and physician office services decreased significantly after the service was implemented. The changes in medical service utilization resulted in reductions in health plan expenditures that exceeded the plan's costs of providing the service. The plan's estimated return for every dollar invested in the nurse triage service was approximately $1.70. CONCLUSIONS: The telephone based nurse triage service appears to be a cost-effective intervention that improves access to medical advice, thereby encouraging appropriate use of medical services. The service is associated with reductions in utilization of hospital ED and physician office services and with high levels of member satisfaction. PMID- 11216334 TI - Cost-effective treatment of depression with selective serotonin reuptake inhibitors. AB - OBJECTIVE: To compare factors that influence cost of antidepressant therapy between older tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) and among drugs in the SSRI class. STUDY DESIGN: Literature review. RESULTS: Pharmacoeconomic data from the primary care and managed care settings demonstrate that the higher acquisition cost of the SSRIs is offset by reduced medical utilization because of a lower incidence of treatment-related adverse events, drug switching, and dosage adjustments than among patients taking TCAs. Analysis of pharmacy claims data suggests that drug acquisition costs, use of concomitant medications, incidence of dose titration, frequency of multitablet therapy (dose stratification), and duration of therapy are the key factors in determining the cost of SSRI therapy. Among the established SSRIs, drug acquisition costs are lowest for paroxetine and sertraline. Costs for concomitant medications may vary by healthcare plan. Recent reports indicate that paroxetine is associated with a low incidence of dose titration. Paroxetine and sertraline are available in extended dosage forms to reduce the need for multitablet therapy. Duration of therapy with all SSRIs is typically shorter than recommended. CONCLUSION: Antidepressant therapy with SSRIs has been shown to be more cost effective than treatment with TCAs when overall healthcare utilization and expenses are considered. PMID- 11216335 TI - Studies demonstrating improved outcomes in patients with asthma: a 10-year review. PMID- 11216336 TI - What Catholic social teaching says to Catholic sponsors of church plans. PMID- 11216337 TI - Unconstitutional or impossible: the irreconcilable gap between managed care and due process in Medicaid and Medicare. PMID- 11216338 TI - Is there a ceiling cap on your health care? Life after Doe v. Mutual of Omaha. PMID- 11216339 TI - Long-term care after Olmstead v. L.C.: will the potential of the ADA's integration mandate be achieved? PMID- 11216340 TI - Health is a human right: why the U.S. immigration law response to gender-based asylum claims requires more attention to international human rights norms. PMID- 11216341 TI - Legal implications of lay use of automatic external defibrillators in non hospital settings. PMID- 11216342 TI - The viatical settlement industry: betting on people's lives is certainly no "exacta". PMID- 11216343 TI - The Family and Medical Leave Act: well meaning legislation meets the strong arm of the constitution of the United States. PMID- 11216344 TI - Caveat emptor: regulating the online medicine man in the new frontier. PMID- 11216345 TI - Informed consent for neonatal circumcision: an ethical and legal conundrum. PMID- 11216346 TI - Health, heart and mind: the contributions of Richard A. Posner to health law and policy. PMID- 11216347 TI - Leader of the Seventh. PMID- 11216348 TI - Judge Posner through dissenting eyes. PMID- 11216349 TI - Micro and macro approaches to local and global problems. PMID- 11216350 TI - Doctor Janeway and the Cameroon project. PMID- 11216351 TI - The joys of international work. PMID- 11216352 TI - A working visit to a developing country. PMID- 11216353 TI - Doctor Cynthia. PMID- 11216354 TI - Looking back fifty years. PMID- 11216355 TI - Bluebird. PMID- 11216356 TI - A man committed to helping to prevent a nation from dying. PMID- 11216357 TI - Affirmative action in medical school admissions: minority underrepresentation in medicine. PMID- 11216358 TI - Diversity in medicine is key to improving America's health. PMID- 11216359 TI - Occupational therapists and research: lessons learned from a qualitative research course. PMID- 11216360 TI - The future of computer access. PMID- 11216361 TI - Choosing books to guide evidence-based practice. PMID- 11216362 TI - From student to therapist: exploring the first year of practice. AB - OBJECTIVES: The transition from classroom to clinical practice challenges many health professional students. This study used a phenomenological approach to explore the lived experience of rehabilitation students during their final placement and first year of practice. METHOD: Students (n = 6) in occupational therapy and physical therapy wrote reflective journals every 2 weeks during their final fieldwork placement and first year of practice. The researchers independently analyzed the journals for common themes. An independent peer completed a blind analysis of two journals. Data were also compared with published first-person accounts of novice practitioners. RESULTS: The lived experience of the first year of practice included four consecutive stages: Transition, Euphoria and Angst, Reality of Practice, and Adaptation. Themes from the journals included great expectations, competence, politics, shock, education, and strategies. CONCLUSION: Recognizing the stages in the process of transition from student to therapist may assist in educational curriculum development and clinical support and supervision for new graduates. Educators need to continue to make education practice relevant while maintaining a theoretical perspective. PMID- 11216363 TI - Variables affecting the competency maintenance behaviors of occupational therapists. AB - OBJECTIVE: The purpose of this study was to examine the relationship between work environment and the competency maintenance activities of occupational therapists. METHOD: A survey of 121 occupational therapists in three states and interviews with 8 occupational therapists in Ohio were used. RESULTS: Analysis of survey data indicated that workplace support and the degree of competency monitoring are significant determinants of competency maintenance behavior. State continuing education requirements had no impact on reported levels of competency maintenance. Personal motivation of the therapist emerged as a potentially important moderator of the relationship between environment and competency maintenance. CONCLUSIONS: Although environmental factors enhance competency maintenance activities, active participation in competency maintenance is also related to the personal commitment of the individual therapist. Strategies that reduce barriers to effective competency maintenance and promote a culture of continuing competency in the profession merit further investigation. PMID- 11216364 TI - Occupational therapy goal achievement for persons with postacute cerebrovascular accident in an on-campus student clinic. AB - OBJECTIVES: A retrospective study was conducted to determine to what extent persons with postacute cerebrovascular accident (CVA) made progress toward rehabilitation goals during occupational therapy treatment and whether age and time since CVA onset affected the rate of goal achievement. METHOD: Data were collected from the admission and discharge records of persons with CVA who had received occupational therapy at a university clinic, who were at least 8 months post CVA, and who had not received therapy in the community for at least 6 months. The treatment was provided by occupational therapy students under supervision and had a mean length of 12 1-hr sessions over one semester. A sample size of 85 was obtained from 13 years of clinic records. RESULTS: All patients in the sample except one made progress toward at least one of their selected rehabilitation goals. The group mean score for goal progress indicated that as a whole, the patients made significant gains. In addition, independent t tests showed no significant differences in mean scores between younger and older patients, between longer and shorter times since onset, between men and women, or between right and left CVA. There was no significant linear association between mean score and the number of treatments received. CONCLUSION: Patients with CVA showed progress toward rehabilitation goals during postacute treatment. Patients with recent CVA onset or of younger age did not achieve goals at a significantly higher rate than those with less recent onset or of greater age. PMID- 11216365 TI - Clinical interpretation of "occupational therapy goal achievement for persons with postacute cerebrovascular accident in an on-campus student clinic". AB - Occupational therapy practitioners, educators, and researchers can gain important information from Lavelle and Tomlin's study for initiating programs that meet the needs of a population of persons who typically cannot access occupational therapy services. The study provides evidence of the effectiveness of occupational therapy for persons with postacute CVA for clinicians seeking alternative funding for community-based practice. The study also suggests that the free university clinic in which Lavelle and Tomlin's research took place was providing a valuable service to persons living near the university, creating important links between the university and the community in which it resides. Lastly, the study raises intriguing questions that provide research opportunities for occupational therapy practitioners, educators, and students that can enhance our understanding of the impact of occupational therapy services on persons long after a CVA. PMID- 11216366 TI - Training to improve awareness of disabilities in clients with unilateral neglect. AB - OBJECTIVE: Awareness of disabilities is known to be a central problem of rehabilitation among clients with large right cerebrovascular lesions and unilateral neglect. The aim of this study was to evaluate the effect of an intervention program focused on improving the awareness of disabilities in four participants with unilateral neglect. The intervention program developed for this study was based on the assumption that awareness of disabilities is a prerequisite for being able to learn and use compensatory techniques in the performance of activities of daily living (ADL). METHOD: The study followed a single-case experimental ABA design. The Assessment of Awareness of Disability was used to measure awareness of disabilities; the Assessment of Motor and Process Skills was used to measure ADL ability; and neuropsychological tests were used to assess unilateral neglect and sustained attention. The intervention program used meaningful and purposeful occupations as therapeutic change agents to improve awareness of disabilities. RESULTS: Awareness of disabilities and ADL ability improved in all four participants; unilateral neglect decreased in three participants; and sustained attention improved in two participants. CONCLUSION: The preliminary findings indicate that training to improve awareness of disabilities might improve the ability to learn the use of compensatory techniques in the performance of ADL in clients with unilateral neglect. The effects of the intervention strategy need to be evaluated further in future research. PMID- 11216367 TI - The Movement Assessment Battery for Children: a comparison of 4-year-old to 6 year-old children from Hong Kong and the United States. AB - OBJECTIVE: There is little information available on the appropriateness of tests developed in the West for children of different ethnicities. The aim of this study was to examine the suitability of the Movement Assessment Battery for Children (Movement ABC) for use with Hong Kong Chinese preschool children. METHOD: The performance of 255 Hong Kong Chinese children between the ages of 4 years and 6 years was compared with that of the 493 children of the same age from the United States who took part in the most recent standardization of the Movement ABC. RESULTS: The test content was found to be suitable for use with Hong Kong Chinese children. However, cross-cultural differences were found on a number of the test items. Chinese children performed significantly better on items contained in the manual dexterity and dynamic balance sections, whereas American children were better at the projection and reception of moving objects. CONCLUSION: These findings highlight the need to ensure that norms for all tests are appropriate for the specific cultural groups being assessed. PMID- 11216368 TI - The comparison of motor performance between part and whole tasks in elderly persons. AB - OBJECTIVE: When teaching clients a multistep functional task, therapists tend to break down the task into part tasks with discrete movements. The purpose of this study was to compare the kinematic performance between part and whole tasks in elderly persons. METHOD: A counterbalanced repeated-measures design was used. Twenty elderly persons without motor problems (7 men, 13 women) performed a signature task in two conditions. For the part-task condition, the participants did the task in a step-by-step manner: (a) reach for a pen, (b) bring the pen to the paper, and (c) sign the name. For the whole-task condition, the participants performed the task in an integrated continuous flow. Kinematic performances for two movement segments (i.e., reaching for the pen, bringing the pen to the paper) were compared between conditions. RESULTS: Generally, the whole-task condition elicited a more efficient, more forceful, and smoother movement than the part task condition. CONCLUSION: The results suggest the importance of keeping a multistep functional task whole. PMID- 11216369 TI - Changes in health status for persons with wrist or hand impairments receiving occupational therapy or physical therapy. AB - OBJECTIVE: The purpose of this study was to describe changes of health status as perceived by clients with hand or wrist impairments who received rehabilitation in acute, orthopedic outpatient facilities from occupational therapy or physical therapy personnel. METHOD: One thousand three hundred ninety-nine adults with wrist (n = 692) or hand (n = 707) impairments who were treated between July 1996 and June 1997 were selected from the Focus On Therapeutic Outcomes, Inc. (FOTO) national rehabilitation database. Each client completed a health status questionnaire on intake and discharge. Data consisted of number of outpatient visits, duration of treatment episode, and health status scores for six functional scales. Measures of intensity, global health status, global utilization, and client satisfaction were calculated. Outcomes were evaluated across occupational therapists and physical therapists. RESULTS: Clients perceived improvement (p < .05) in their health status over the course of therapy. Number of visits and measures of health status and client satisfaction were similar across type of therapist. Episode duration was longer (p < .05) and intensity was less (p < .05) for clients seen by occupational therapists. CONCLUSION: Clients receiving rehabilitation in acute orthopedic outpatient centers perceived improvement in their functional abilities and health and well being (global health status and individual functional scales) over the time during which treatment was provided. Results confirm the responsiveness of the outcomes instrument to clinical change in the clients' perception of their health status over the course of therapy and support the use of health status as a measure of clinical outcome. PMID- 11216370 TI - The Adult Sensory Profile: measuring patterns of sensory processing. AB - OBJECTIVE: This article describes a series of studies designed to evaluate the reliability and validity of the Adult Sensory Profile. METHOD: Expert judges evaluated the construct validity of the items. Coefficient alpha, factor analysis, and correlations of items with subscales determined item reliability, using data from 615 adult sensory profiles. A subsample of 20 adults furnished skin conductance data. A heterogeneous group of 93 adults completed the revised Adult Sensory Profile, and item reliability was reexamined. RESULTS: Expert judgment indicated that items could be categorized according to Dunn's Model of Sensory Processing. Results suggested reasonable item reliability for all subscales except for the Sensation Avoiding subscale. Skin conductance measures detected distinct patterns of physiological responses consistent with the four quadrant model. Revision of the Adult Sensory Profile resulted in improved reliability of the Sensation Avoiding subscale. CONCLUSION: The series of studies provides evidence to support the four subscales of the Adult Sensory Profile as distinct constructs of sensory processing preferences. PMID- 11216371 TI - Team collaborative practices between teachers and occupational therapists. AB - OBJECTIVE: A descriptive, correlational study using a survey instrument and record review was designed to describe collaboration practices between teachers and occupational therapists in public schools and to explore relationships of these practices to individual education plan (IEP) objectives and teachers' perceptions of occupational therapy contributions to student skill development. METHOD: Forty teachers of students who receive occupational therapy comprised the sample. Descriptive statistics and Spearman rank order correlations were used to describe the practices and to determine associations among the variables. RESULTS AND CONCLUSIONS: The findings indicated that teachers and occupational therapists were using collaborative team practices, such as jointly developing goals and objectives, collaboration within the classrooms, jointly monitoring interventions, and jointly reviewing student progress. However, scheduling team meetings was difficult. The majority of respondents stated that occupational therapy contributed to student skill development, and as collaboration practices increased, the teachers' perceptions of occupational therapy contribution to student skill development increased. A significant negative correlation was found between the percentage of IEP objectives met variable and three collaborative variables--team meetings, reviewing progress, and develop goals and objectives. This finding indicated that as the frequency of these team processes increased, fewer objectives were met. PMID- 11216372 TI - The experience of clinician-researchers in occupational therapy. AB - This study examined the experience of occupational therapy clinicians who do research to illuminate factors that influenced their research, the processes involved, and the outcomes. The qualitative approach of grounded theory was used. Purposive sampling of all research-productive clinicians in acute care hospitals in one Australian city occurred. Fifteen clinicians participated in in-depth interviews that explored their experiences of research. Results were analyzed with the constant comparative method, and six conceptual categories were developed. These categories were further analyzed in terms of their relationships, and a core category that explained and synthesized the data was identified--becoming a clinician-researcher. This category encompassed a process of role change during which the person changed from clinician to clinician researcher. Conditions for this change were identified, and three key concepts were derived to elaborate the core category. In becoming a clinician-researcher, the person was active in (a) identifying research as significant, (b) constructing actions in relation to research, and (c) evaluating the experience. The findings further the understanding of clinician-researchers through the description of their experience and the empirically based theoretical formulation that explains it. PMID- 11216373 TI - Occupation as means to mental health: a single-case study. PMID- 11216374 TI - Building an occupational therapy library collection. PMID- 11216375 TI - Effect of treatment on growth in congenital adrenal hyperplasia. AB - In 22 patients with congenital adrenal hyperplasia (CAH), the effect of treatment on growth was evaluated retrospectively. The degree of control with treatment had generally been assessed by measurements of serum 17-hydroxyprogesterone (17-OHP) and/or urinary pregnanetriol levels. In 20 patients, there were no significant differences in both height SDS for bone age (-2.05 +/- 1.89 vs -1.85 +/- 1.30) and height SDS for chronological age (CA) (0.23 +/- 1.94 vs -0.36 +/- 1.81) in a mean uninterrupted treatment period of 5.80 +/- 3.58 years. Further analysis in salt-losers and nonsalt-losers separately showed that height SDS for bone age had decreased in the salt-losers and had increased in the nonsalt-losers. Six patients had signs of early puberty. In 22 patients, there was a negative correlation between the prednisolone dose on one hand and height velocity SDS for CA and bone age velocity on the other. It was also found that the mean serum levels of 17-OHP did not always reflect the degree of long term control measured by auxological parameters. These findings indicate that our treatment in the patients did not result in a significant improvement in height prognosis. We can conclude that growth prognosis in CAH patients can be improved by relying on auxological parameters rather than serum 17-OHP and urinary pregnanetriol levels for monitoring control. Special attention should be paid to salt-losers in this respect. PMID- 11216376 TI - Intellectual psycho-educational and functional status of low birth weight survivors beyond 5 years of age. AB - To determine the intellectual, psycho-educational and functional status of low birth weight (LBW) survivors (birth weight < or = 2000 gms) beyond 5 years of age and to compare their status with normal birth weight counterparts. This was cross sectional study. On hospital based cohort on longitudinal follow-up at the High Risk and Well Baby Clinics of a teaching hospital. The demographic data of these children was recorded. A detailed physical examination was performed. The tests of cognition included the Stanford Binet and the Raven's Progressive Matrices. Academic achievement was evaluated by the Wide range achievement test-Revised (WRAT-R). Assessment of visuo motor integration was done by the Bender Gestalt Test. The proportion of children having soft neurological signs was determined. Vineland Social Maturity Scale was performed on all children. Fifty-nine LBW children and fifty-seven matched control children participated in the study. 27 of LBW children were examined at a mean age of 7.0 +/- 1.1 years (group I) and 32 were examined at a mean age of 10.6 +/- 1.2 years (group II). The LBW children as a group performed in the normal range on the tests of cognition and academic achievement, but were significantly disadvantaged (p < 0.005) as compared to controls. A higher percentage of LBW children had low scores on the Bender Gestalt. Test as compared to controls but the difference was not significant. A significantly higher proportion of LBW children of both the groups showed the presence of soft neurological signs as compared to controls. The social quotient as assessed by the vineland Social Maturity Scale was significantly lower in the LBW children as compared to controls. Thus, though the LBW children were performing in the normal range on various measures, comparison with the control group showed that they were clearly disadvantaged on nearly every measure tested, emphasizing the need for early detection and referral for special education. PMID- 11216378 TI - Spectrum of respiratory distress in very low birthweight neonates. AB - The incidence, etiology and the outcome of respiratory distress in 243 consecutive liveborn very low birth weight neonates (VLBW) were analysed. One hundred and forty six (60%) VLBW neonates developed respiratory distress. Hyaline membrane disease, congenital pneumonia and transient tachypnea of the newborn were the major underlying causes (35.6%, 28.1%, and 27.4% respectively). The mortality rate was significantly higher in neonates with respiratory distress (72 of 146, 49.3%) than in those without distress (28 of 97, 28.8%) (p < 0.05). This difference was more sharply reflected in the 1000-1249 birth weight group and in the 29-32 weeks gestation group. Respiratory distress is a significant determinant of VLBW mortality. PMID- 11216377 TI - Body proportions in Fanconi anemia heterozygotes. AB - To study the anthropometric ratios in parents (heterozygotes) of children with Fanconi anemia. The study was carried out in the Department of Hematology, Institute of Child Health & Hospital for Children, Chennai. Parents of children with Fanconi anemia were the subjects of the study. Applying standard instruments and methods, various body measurements were recorded. 31 fathers and 37 mothers were included in the study. A hundred male and female controls of the same ethnic group were also studied for the same parameters. The ratios were calculated and statistically analyzed. It was observed that fathers (male heterozygotes) had shorter forearms, the ratio of upper arm: forearm was significantly increased compared to male controls. In mothers (female heterozygotes) the inter-pupillary distance was increased, the ratio of head circumference to inter-pupillary distance was decreased compared to female controls. PMID- 11216379 TI - Oxidative stress, phototherapy and the neonate. AB - Phototherapy is the most widely used form of therapy for unconjugated hyperbilirubinaemia. Its non-invasive nature and few side effects reported earlier have led to the assumption that it is innocuous. Recent research has revealed that phototherapy is a photodynamic stress and can induce lipid peroxidation. There is increasing evidence that many severe diseases of the neonate are caused by oxidative injury and lipid peroxidation. In the present communique, we review the oxidative susceptibility of the neonate and the evidence now available that phototherapy induces oxidative stress. Although intensive phototherapy (up to 40 mwatt/cm2/nm) has been reported to be increasingly effective, a little caution, we believe is warranted, till more definite data in the human neonate, help resolve the issue. PMID- 11216380 TI - Challenges in human genetics in India in the new millennium. AB - This editorial provides information on the first draft of the human genome, and examines the impact this will have on the practice of medicine, with special reference to India. It examines what is currently possible in India, what we should do in the immediate future, and what is in store in the long run. The future is indeed bright and India needs to expand the genetic services and research facilities. PMID- 11216381 TI - Prenatal diagnosis and treatment of steroid 21-hydroxylase deficiency (congenital adrenal hyperplasia). AB - Steroid 21-hydroxylase deficiency congenital adrenal hyperplasia is the most common cause of genital ambiguity in females at birth. Inhibited formation of cortisol causes increase in the release of ACTH in turn leading to overproduction of adrenal androgens. This predisposes the affected female fetus to prenatal development of genital ambiguity. A large number of patients also have aldosterone insufficiency which manifests after birth in form of inability to conserve sodium and to excrete potassium which can lead to adrenal shock and neonatal death, if left untreated. Prenatal diagnosis is possible using several methods like steroid assay of amniotic fluid and, HLA typing. Recently with advancement more accurate direct molecular genetic techniques have been utilized on chorionic villus samples in first trimester of pregnancy. Prenatal treatment is also possible and pregnancies can be managed by administering dexamethasone to the mother as soon as pregnancy is diagnosed. This suppresses fetal androgen production in genetic females preventing virilization and leading to normal development. Prenatal diagnosis and treatment are highly desirable in families with a positive family history towards birth of a child without features of the disease. PMID- 11216382 TI - Diagnostic approach to children with birth defects. AB - Clinical genetics deals with the diagnosis, management and prevention of genetically determined disorders. Our current understanding of the role genes play in the pathogenesis of everything from fetal malformation to neurodegenerative and malignant disorders of late adulthood make it somewhat difficult to draw a clear boundary for this rapidly expanding specialty. With the recent completion of a preliminary draft of the entire sequence of the human genome it is not unreasonable to dream of novel therapeutic approaches such as "gene therapy", to cure disorders heretofore treatable with supportive measures only. Nevertheless, the clinical assessment of the patient will continue to be the cornerstone of good practice of medicine. In this article we review a clinical approach to the diagnostic challenge presented by children with birth defects. The principles we illustrate apply to other aspects of "genetic medicine" as well. PMID- 11216383 TI - Advances in laboratory evaluation of Turner syndrome and its variants: beyond cytogenetics studies. AB - Turner syndrome is a clinically defined phenotype that is characterized by partial or complete X chromosome monosomy. A host of cytogenetic aberrations and mosaicism have been associated with this syndrome. Some individuals, Turner syndrome variants, have cytogenetic findings consistent with Turner syndrome, but exhibit atypical clinical phenotypes. Recently, several molecular tests have been presented to allow for the refined clinical study of Turner syndrome and its variants. PMID- 11216384 TI - Medical genetics in primary health care. AB - Medical genetics has been at the forefront of developments in medicine for the last 50 years. This progress has mainly benefited industrialized countries. Due to continuing improvements in the socio-economic and health indices in developing nations more than half of them have now reached a stage where it has become relevant for them to initiate and develop medical genetic services. The WHO foresaw this eventuality in 1985 and further recognised the need to develop community based medical genetic services that are relevant to and can be incorporated into primary health care. The need for primary health care based medical genetic services has subsequently also been accepted in industrialized nations. This paper summarises those primary health care based interventions that can be undertaken to ensure the control of genetic disorders and birth defects. PMID- 11216386 TI - Radial artery cannulation in neonates: a new method. AB - In neonates arterial cannulation is a relatively difficult procedure without the aid of transillumination. This paper discusses a simple method to make the radial artery prominent in neonates. The principle used is displacement of perivascular interstitial fluid to make the course of the artery visible so that, under direct vision, cannulation of the artery becomes almost as easy as a venous cannulation. PMID- 11216385 TI - Advances in management of meconium aspiration syndrome. AB - Meconium Aspiration Syndrome (MAS) is a leading cause of respiratory distress in the newborn. Antenatal diagnosis of meconium stained amniotic fluid and fetal distress is important to reduce morbidity and mortality in the neonates. Amnioinfusion of saline and tracheal suctioning of meconium are preventive interventions. Babies with MAS who continue to have respiratory distress need to be put on conventional ventilators. Increasing hypoxia, hypercarbia and barotrauma warrants changing to high frequency oscillatory ventilation. Pulmonary hypertension is an important complication which should be promptly recognized. Nitric oxide therapy used with high frequency ventilation has improved the outcome of babies with severe MAS and pulmonary hypertension. Some of these babies who continue to worsen clinically need to be put on ECMO circuit. Surfactant infusion in babies with MAS has been shown to improve gas exchange, resolve pulmonary hypertension and decrease oxygenation index. Total and partial liquid ventilation with perflurocarbon improves oxygenation, increases lung expansion and increases pulmonary blood flow in model studies of animals with MAS. Surfactant infusion and liquid ventilation are newer promising modes of therapeutic interventions in babies with severe MAS. PMID- 11216387 TI - Idiopathic origin of meconium peritonitis. AB - A 26-year-old, gravida 3 presented at 31 weeks of gestation with polyhydramnios. On ultrasound there was marked foetal ascitis with unilateral hydrocele. Patient delivered a 3.15 kg, large-for-date baby at 33 weeks and 3 days of gestation. On basis of clinical, radiological and sonographic features, diagnosis of meconium peritonitis was made. Ascitic tapping was done. Surgery was withheld, as there were no signs of intestinal obstruction. DNA testing for cystic fibrosis was negative. Baby did not deteriorate so he was discharged. Baby was doing well on 2 months follow up. Hydrocele and ascitis were resolving. Rarely meconium peritonitis may occur without an underlying cause when peritonitis may be innocuous and intervention may not be required. PMID- 11216388 TI - Endolaryngeal foreign bodies. AB - Unusual foreign bodies of the larynx viz. a toy gear, a metallic spring, a safety pin, a piece of stone, lodged in the endolaryngeal region are reported. Radiographic documentation with the rare feature of absence of symptoms inspite of lodgement for long duration is recorded. PMID- 11216389 TI - Intrauterine intussusception--a cause for ileal atresia. AB - A case of ileal atresia consequent to intrauterine intussusception is reported. The baby presented with features of neonatal intestinal obstruction but signs of peritonitis were absent. The intussusception was discovered on gross examination of distal atretic ileal segment. The case was managed successfully by resection and end to back anastomosis. This case is reported to highlight intrauterine intussusception as one of the causes of ileal atresia. PMID- 11216390 TI - Askin tumor: a malignant small cell tumor. AB - Malignant tumours of the chest wall are rare in the pediatric age group. Askin tumour, a primitive neuroectodermal tumour with aggressive nature, is extremely rare. Clinico-pathological features make it quite distinct from Ewing's sarcoma. Aggressive nature of the tumour results in short clinical presentation of the patient. Diagnosis of Askin tumour is mainly by histo-pathology. Imaging modalities play only a complimentary role. We present a case diagnosed to have this rare malignant tumour in the thoraco-pulmonary area in a child. PMID- 11216391 TI - Mesenteric leiomyoma in infancy. AB - Leiomyoma of the mesentery is an uncommon tumor. This has been documented in adults and children. However, there is no such case reported in an infant, which is being presented in this report. PMID- 11216392 TI - Familial hyperphosphatasemia. PMID- 11216393 TI - MtDNA haplogroups in the populations of Croatian Adriatic Islands. AB - The number of previous anthropological studies pointed to very complex ethnohistorical processes that shaped the current genetic structure of Croatian island isolates. The scope of this study was limited to the general insight into their founding populations and the overall level of genetic diversity based on the study mtDNA variation. A total of 444 randomly chosen adult individuals from 32 rural communities of the islands of Krk, Brac, Hvar and Korcula were sampled. MtDNA HVS-I region together with RFLP sites diagnostic for main Eurasian and African mtDNA haplogroups were analysed in order to determine the haplogroup structure. The most frequent haplogroups were "H" (27.8-60.2%), "U" (10.2-24.1%), "J" (6.1-9.0%) and "T" (5.1-13.9%), which is similar to the other European and Near Eastern populations. The genetic drift could have been important aspect in history, as there were examples of excess frequencies of certain haplogroups (11.3% of "I" and 7.5% of "W" in Krk, 10.5% of "HV" in Brac, 13.9% of "J" in Hvar and 60.2% of "H" in Korcula). As the settlements on the islands were formed trough several immigratory episodes of genetically distant populations, this analysis (performed at the level of entire islands) showed greater genetic diversity (0.940-0.972) than expected at the level of particular settlements. PMID- 11216394 TI - Microsatellite haplotypes associations with 5 CFTR mutations in "Grande Briere", an isolate located in southern Brittany. AB - The variability at three microsatellites in the Cystic Fibrosis Transmembrane Conductance Regulator Gene (CFTR) locus has been studied for frequent mutations encountered in an isolated population of "Grande Briere", a small region located in Southern Brittany. Fluorescent multiplex PCR of these microsatellites were assayed in 16 Cystic Fibrosis (CF) families carrying 5 different mutations. The four most frequent haplotypes on df508 chromosomes were the same as those found in Northern France and Europe but the distribution of these haplotypes provides new enlightenment on the population origin of this insular community. PMID- 11216395 TI - Characteristics of myotonic dystrophy in Istria: molecular genetic approach. Part II: Analysis of genetic polymorphisms. AB - One of the world highest prevalence estimates of myotonic dystrophy (DM) has been reported in the Croatian region Istria. To analyse the population genetic characteristics of DM locus in Istria, two intragenic and three extragenic polymorphic markers were tested. The Southern blot technique was used for D19S63 locus analysis, whereas PCR analysis was performed for CKMM, Alu polymorphism, DMPK (G/T) intron 9/HinfI polymorphism, and D19S207 genetic markers. The compound haplotypes segregating with DM were established. A complete association between the DM mutation and D19S63, D19S207, intron 9/HinfI polymorphism and Alu polymorphism markers were found. In all DM chromosomes: D19S63 and Alu markers had the allele 1 in common; D19S207 had the allele 3 in common, DMPK (G/T) intron 9/HinfI marker had the allele 2 in common. The analysis of CKMM polymorphism revealed genotype heterogeneity; in DM chromosomes either allele 2 or allele 4 were found. The haplotype analysis in the population of Croatian Istria supports the linkage disequilibrium between the DM mutation and Alu polymorphism, intron 9/HinfI polymorphism, D19S63 and D19S207 markers as reported worldwide. The results of the haplotype analysis suggest a common origin of the mutation in Istrian population. PMID- 11216396 TI - Anthropogenetical analysis of abnormal human alpha-globin gene cluster arrangement on chromosome 16. AB - An earlier study of human globin gene polymorphism in two Adriatic islands of Olib and Silba showed an abnormal arrangement of alpha-globin genes in two different individuals. The next step was to determine the degree of the kinship relationship between the two probands, one with a deleted and another with triplicated alpha-globin gene on the island Silba, and to determine the stability of this disorder through generations. We reviewed the parish registers (Status Animarum) of the island of Silba, dating from the year 1527, and constructed family trees for the two probands. Restriction endonuclease mapping was performed to study the arrangement of the alpha-globin genes in the offspring of our probands. A total of 183 ancestors completed the two family trees. The kinship relationship between them was established in the 5th, 6th, and 7th generation. The analysis of alpha-globin genes in the offspring of our probands showed the triplicated alpha-globin genes in two persons. We also found alpha-globin gene triplication in other three relatives. We did not find any deleted alpha-globin genes. We determined the kinship relationship between the two probands, one with deleted and the other with triplicated alpha-globin genes. This finding enabled us to determine the stability of this gene disarrangement through generations. It also showed new possibilities in anthropogenetic research, by combining the analyses of parish registers with those of modern genetic methods, such as restriction endonuclease mapping. PMID- 11216397 TI - HLA class I polymorphism in the Albanian population. AB - The HLA class I polymorphism was studied in a sample of the Albanian population. Ninety-three unrelated healthy Albanians were typed for HLA-A, -B and -Cw antigens by standard microlyphocytotoxicity test. The antigens with the highest frequencies were: HLA-A2 (34.4%), A3 (14.5%) and A1 (12.4%); B51 (19.3%), B35 (12.4%) and B18 (10.2%); Cw4 (16.2%), Cw7 (16.2%) and Cw6 (10.8%). The HLA haplotypes with high frequency in Albanians included A2-B51 (4.3%), A2-B18 (2.4%), A2-B35 (2.4%), Cw4-B35 (7.6%), and Cw7-B18 (6.5%), which are not significantly different from the other neighboring populations. Low frequency of HLA-A1-B8 haplotype (1.1%) is noted in the Albanian population. The frequency of HLA-B27 antigen (1.1%) is one of the lowest frequencies observed in Caucasians. Such results are important in studies of HLA-A1-B8, HLA-B27 and disease associations. These findings should be also useful in understanding the origin of Albanians, representing a base for future studies about HLA polymorphism in the Albanian population. PMID- 11216398 TI - How many markers or how many alleles per system are appropriate in zygosity testing? AB - Due to the development in DNA-PCR-technique more and more systems with a high number of alleles have been established in twin diagnosis. Because of their high effectiveness in resolving of genetic questions it is not amazing that some authors have postulated the thesis that typing of 5 to 10 DNA-PCR systems can prove monozygosity. For this paper the use of different systems (conventional and PCR systems) has been tested for twin diagnosis and the observed effects are discussed. PMID- 11216399 TI - Anthropological cybernetic model of demography of the island of Hvar. AB - Intentions of the present investigation were to apply a cybernetic model in description of demography on the island of Hvar for a time period from year 1800 till now. The basic idea of the model applied in this anthropological study (LOPI) is that the rate of reproduction is given by the non-linear controller: Y2/Te(1-(Y3/G)). Constant G represents an environmental carrying capacity of a community with respect to the cohort of older people (no longer a part of the pool of reproductive inhabitants; Y3) sharing limited survival resources. The proportional constant 1/Te connected with the pool of reproductive inhabitants (Y2) correspond to the reproduction maximum. The consistency of the model is evaluated through comparison between model data and census. The LOPI model describes incredibly well the demography of the island of Hvar from the year 1800 till 1940. After year 1950 there were more inhabitants on the island then the model would predict. This fact is connected with changes in the migration or also in the increased carrying capacity (G). On the basis LOPI model, population dynamic oscillates in its development. The example of the island of Hvar has proved that population reaches a maximal number of inhabitants every 200 years. The oscillation of population dynamics is influenced by the migration processes. The mere fact that oscillating population size is connected to population genetics and probably also to sociocultural factors suggests that a cybernetics demographic model can be a guide in the holistic anthropological approach. PMID- 11216400 TI - Risk factors in asthmatic patients in Croatia. AB - The aim of this case-control study was to investigate whether some factors, that are associated with development of asthma, are significantly more present in the observed group of asthmatic patients, in comparison to the control group. Participants included 111 cases with asthma, and 108 controls with no asthma. Data obtained from cases and controls were compared according the sex. The study was performed using a specially developed questionnaire and data were collected from medical documentation of cases. Results showed that a significantly high proportion of cases had lower socio-economic status, higher proportion of atopic diseases, and were more exposed to dampness in working environment, and passive smoking, both at home and at work. Cases also exhibited poorer sustainment of physical strains and psychological stresses, and considered their life quality was greatly reduced by asthma. Among asthmatic participants, there were fewer current smokers and non-smokers, and more ex-smokers. PMID- 11216402 TI - Psychosocial characteristics of patients with bronchial asthma and coronary disease: similarities and differences. AB - The authors compare two groups of subjects: patients with bronchial asthma and those with coronary disease, with regard to some social characteristics, abilities and perception of factors which they conceive are important in the etiology of their disease. Data were obtained by means of a questionnaire based on a known calibrated scale. A group of 100 patients with bronchial asthma and a group of 102 patients with coronary disease were examined. The significance of the difference was tested by chi 2, t-test, Wilcoxon's test and multivariate discriminative analysis. The results showed statistically significant differences between the patients with bronchial asthma and those with coronary disease in some social and psychological characteristics and also with regard to perception of potential etiological factors of their disease. However, no difference was found in life style and habits between the coronary and asthmatic patients. PMID- 11216403 TI - Alcoholic drinkers and road safety in the Republic of Slovenia. AB - In this study we were therefore interested in the percentage of road traffic offenses (RTO) and road traffic accidents (RTA) involving inebriated drivers one year before and one year after the passing of the new Law on Road Traffic Safety (LRTS) as well as measures (referrals, punishments and final decisions on the revoking of driver's licenses due to drunk driving). One year before the passing of the new LRTS, there were 40,702 RTA-s in the Republic of Slovenia (12.2% caused by drunk drivers). The average alcohol concentration in exhaled air for those analysed was 1.19 g/kg. One year after the passing of this law there were 36,479 RTA-s (8.6% caused by drunk drivers). The average alcohol concentration in exhaled air for those analysed was 1.32 g/kg (the differences were statistically significant). In 13.8% cases the reason for performing a measurement of the alcohol concentration in exhaled aier was an RTA with an average alcohol concentration in exhaled air of 1.22 g/kg and in 86.2% of cases an RTO with an average alcohol concentration in exhaled air of 1.25 g/kg (the differences were statistically significant). We found it interesting that the number of events minvolving lower concentrations decreased, but the percentage involving higher alcohol concentrations even increased. The results of this study indicate without a doubt that the law was not successful enough with its repressive and preventative measures in the field of drunk drivers. Experts on alcohol believe that punishment cannot make alcoholics and other drivers abandon their behavioural patterns and stop driving under the influence of alcohol. This can be achieved only by treatment, and the present practice (police--misdenveanour counts--repeat general medical check-up) has been ineffective as prevention among alcoholic drivers. We therefore believe that supplements to the LRTS should be adopted urgently, that would contribute, through better medical selection, to a reduction in the number of drunk drivers behind the wheel, both those who are alcohol dependent (and should be referred to treatment). PMID- 11216401 TI - Are respiratory allergic diseases related to atopic dermatitis? AB - The difference of test results between patients with "pure" atopic dermatitis (AD) and "mixed" AD (with concomitant respiratory allergy, RA) was investigated in 30 AD patients. The results showed the onset of disease that mostly occur in the early infancy [15 (50%) patients had developed the disease under the age of 2 2/10 in "pure" AD, and 13/20 in "mixed" AD]. Twenty (66.6%) of them had a history of RA ("mixed" AD) whereas the remaining 10 (33.3%) had "pure" AD. Seventeen (56.6%) AD patients had one concomitant allergic disease, while 3 (10%) patients had two comorbid conditions (AR and AB) each. Family history was positive for atopy in 22 (73.3%) AD patients [in 14 (46.6%) patients in a first-degree relative]. Twenty-four (80%) patients had positive prick test [9/10 (90%) in "pure" AD and 15/20 (75%) in "mixed" AD], mostly for house dust (20). Positive scratch test was observed in 16 (53.3%) patients [4/10 in "pure" AD, and 12/20 in "mixed" AD]. Nineteen (63.3%) AD patients showed positive patch test reaction [5/10 in "pure" AD, and 14/20 in "mixed" AD]. AD patients had higher serum IgE (21/30) than non-atopic ones but similar in "pure" AD, and "mixed" AD [7/10 (70%) in "pure" AD, and 14/20 (70%) in "mixed" AD]. Determination of CD23 marker on B lymphocytes showed normal values in 24, and increased values in six patients [2/10 in "pure" AD, and 4/20 in "mixed" AD]. The values of CD21 were decreased in 16 AD patients [6/10 in "pure" AD, and 10/20 in "mixed" AD]. HLA-DR expression was normal in almost all patients. There were no statistically significant differences (p < 0.05) between the "pure" AD and "mixed" AD patient groups, except for the age at onset, which was younger in the group of patients with concomitant RA. Accordingly, study results pointed to the association between AD and RA. PMID- 11216404 TI - Glaucoma triple procedure: a one-site vs. a two-site approach. AB - The purpose of this study is to describe and evaluate the success rate of combined glaucoma and small cataract surgery by means of a one-site versus two site approach. Fifty-eight eyes of fifty-five patients undergoing combined surgery were operated: thirty-one eyes underwent two-site approach and twenty seven eyes underwent one-site approach. Short term and long term mean intraocular pressure (IOP) was similar in both groups. There was no significant difference in postoperative inflammation and complication rates between two groups. There is no significant difference in the postoperative results in those two different approaches to perform combined operations of cataract and glaucoma. PMID- 11216405 TI - Plasma cholinesterase activity in patients with uterine cervical cancer during radiotherapy. AB - The objectives of this study were to investigate: 1) the activity of pseudocholinesterase (PChE) in patients with uterine cervical cancer in different stages (uterine cervical carcinoma in stages II b and III and recurrent cervical carcinoma in stages III and IV a,b) and to compare it to the enzyme activity in patients with benign tumour of the uterus, and 2) the effects of radiotherapy on enzyme activity in those patients with uterine cervical carcinoma for which the chosen treatment was radical radiotherapy. Thirty patients with uterine cervical carcinoma in stages II b and III (Group A), sixteen patients with recurrent cervical carcinoma in stages III and IV a,b (Group B) and thirty-eight patients with benign tumours of the uterus (control, Group C) were evaluated and their PChE activity was determined prior to any treatment (pre-therapy enzyme activity). All eighty-four patients were free of any liver disease. The results have shown that the patients of Group A had the pre-therapy PChE activity practically identical to those in group C, but patients of Group B had significantly lower values of PChE with respect to enzyme activities of Groups A and C (p < 0.001). That is to say, PChE activity was influenced by the extent to which the malignancy had spread. Radical radiotherapy (up to 8 weeks in doses higher than 50 Gy into point A; average 80 Gy) which was the chosen treatment only for patients from group A did not cause a significant inhibition of PChE activity in any patients in comparison with their control values. With regard to the role of PChE in hydrolysis of succinylcholine, our results about the influence of the malignant disease and the radiotherapy on PChE activity are clinically significant. PMID- 11216406 TI - Safety of simultaneous resections of colorectal cancer and liver metastases. AB - Liver resection is the only potentially curative method for patients with colorectal cancer metastases and 5-year survival rates are 20%-40%. Simultaneous resection of colorectal cancer and synchronous liver metastases has been recommended if minor hepatectomy is indicated. The purpose of this paper is to analyze the treatment of hepatic colorectal secondaries and to assess the safety of simultaneous and delayed liver resections and relations of morbidity to the extensiveness of hepatectomy and perioperative factors. Analyzed were 21 patients with liver metastases from colorectal cancer operated between 1997 and 1999 in the Clinical Hospital "Sestre milosrdnice". Operating time for simultaneous colorectal and liver resections was not significantly longer compared to liver resections alone. No significant difference in complication rate was found after simultaneous procedures and liver resection alone (38% vs. 31%). Complication rate after major liver resections was not significantly greater than after minor resections (38% vs. 31%). No statistically significant differences were found in operation time and blood replacement between patients who developed postoperative complications and those who did not. In conclusion, simultaneous resections of primary colorectal cancer and liver metastases may be considered safe. Morbidity rates are not significantly different from those after liver resections alone, nor depend significantly upon the extensiveness of liver resection, providing that the operation time and blood loss are within the range observed in this study. PMID- 11216407 TI - Early diagnosis and treatment of ectopic pregnancy. AB - During the period from 1995 to 1999, 64 patients were treated for ectopic pregnancy. All patients admitted to the department passed the same procedure including (complete preoperative laboratory findings, Beta HCG, serum progesterone and transvaginal colour Doppler). In patients who had ultrasound finding typical for ectopic pregnancy in combination with positive Beta HCG, conservative treatment was primarily done. In the rest of the patients, Beta HCG was tested every second day and in combination with the clinical and vaginosonographical findings the patients underwent diagnostic or operative laparoscopy. Out of 64 patients 36 had visible ectopic pregnancy when admitted to the clinical department. Three patients had no visible ectopic pregnancy neither at the time of their admission to the department nor at the time of laparoscopy. One of them had cervical pregnancy and the other two had pregnancies in the uterine part of the tube. The patient with cervical pregnancy was treated with metrotrexat (MTX) 12 mg daily in 5 doses. One patient with cornual pregnancy was treated with high doses of oxytocin infusion in combination with MEB intravenously 3 x 1 amp. The other patient with cornual pregnancy underwent laparoscopy with cornual resection and salpingectomy. Four of other tubar pregnancies were treated with metrotrexat 12 mg/day for 5 days. Other ectopic pregnancies were treated as follows: 36 laparoscopic salpingectomies, 10 laparoscopic salpingotomies with ovum expression, 9 adnexectomies by laparotomy, and 2 laparoscopic adnexectomies. PMID- 11216408 TI - Epidemiology of coeliac disease in children in one Croatian county: possible factors that could affect the incidence of coeliac disease and adherence to a gluten-free diet (Part II). AB - Coeliac disease is a life-long disorder characterised by small-intestinal mucosal damage caused by gluten. The treatment, gluten-free diet, leads to mucosal restoration and reduces the risk of malignant and non-malignant complications. According to our recent results, cumulative incidence in Croatian children is 1:519 life-births. Coeliac disease presents early, mostly with typical symptoms. We investigated possible influences of breast-feeding duration and time of gluten introduction on such presentation of the disease. Study included coeliacs born in Medimurje between 1985 and 1994 (N = 31). Patients' adherence to treatment was also studied. Although short breast-feeding (mean 2.9 months) and early gluten introduction (mean 4.9 months) were shown, no correlation was found between those factors and time of the disease presentation. Concerning adherence to gluten-free diet, only 50% of patients maintained it strictly, 23% irregularly, while 27% were on normal diet. In order to improve it, regular follow-ups are recommended. PMID- 11216409 TI - Urban hypothermia and hyperglycemia in the elderly. AB - From December 1993 to March 1999 we treated 18 elderly patients aged 66-87 years, suffering from urban hypothermia: 11 women and 7 men. Ten patients suffered from moderate hypothermia (rectal temperature 32-35 degrees C), and eight from severe hypothermia (rectal temperature < 32 degrees C). Regarding consciousness, in the group suffering from moderate hypothermia, 3 were somnolent and 6 in various degrees of comatose states. In the group suffering from severe hypothermia, 3 patients were somnolent or soporous and 5 in comatose states of various degrees. Values of arterial blood pressure in the group with moderate hypothermia was normal in one, in 3 arterial hypotension was observed and 6 were in a state of shock. In the group with severe hypothermia, 3 presented arterial hypotension and 5 were in a state of shock. In the group with moderate hypothermia the blood glucose level was elevated in six: 9.3-10.2-10.7-17.9-21.3-99.0, and in one patient the blood glucose level was low: 2.3 mmol/L, in correlation with hypoglycemic coma. In the group with severe hypothermia in all eight patients the values were elevated: 6.7-7.4-7.6-8.7-9.1-11.2-12.4-17.9 mmol/L. PMID- 11216410 TI - Overweight and fatness in Dalmatia, Croatia: comparison with the U.S. population reference. AB - Subscapular skinfold, elbow breadth and upper arm indicators of nutritional status were studied in the population of Dalmatia in Croatia. Age- and sex specific percentiles were obtained from 4373 subjects, 18 to 74 years of age, and compared to the U.S. NHANES I and II reference data. There were significant differences between these data sets in all studied variables. The results complement those reported previously for BMI and triceps skinfold and indicate that high prevalence of overweight in Dalmatians largely reflects their muscularity and skeletal robustness rather than excess body fatness. The findings suggest that the U.S. upper percentiles of BMI and skinfolds are inadequate for the assessment of excess body fatness in Dalmatian population. The obtained population-specific percentile distributions should be used provisionally as the reference data for group comparisons in the Dalmatian region. PMID- 11216411 TI - Nutrition, infection and child growth in Papua New Guinea. AB - Growth patterns of populations in Papua New Guinea (PNG) have traditionally shown considerable variation, with the greatest difference lying between coastal and highland populations. While genetic differences in explaining these patterns cannot be excluded, the generally poor growth relative to western growth references is largely due to the complex interactive effects of undernutrition and infection. The effects of diet, nutrition and infection on the nutritional status of a child vary with age, the general disease ecology and the type and extent of exposure to it, patterns of infant and young child feeding, and types of food consumed. There are two possible ways in which the relationship between undernutrition and infection can begin; one in which poor nutritional status leads to impaired immunocompetence and reduced resistance to infection, and the other in which exposure to infectious disease can lead to a range of factors that reduce food intake, absorption of nutrients, or increase nutrient requirements. In PNG prior to, and at early stages of modernisation, primary malnutrition is likely to have been the usual initiating factor in the onset of growth faltering due to undernutrition-infection interactions. However, the possibility that infection may have been the initiating event in some societies cannot be excluded. This would have happened by way of early dietary supplementation of infants with foods of minor nutritional significance, which could have acted as a vehicle for the introduction of infectious disease to the child. With modernisation and adoption of primary health care principles, earlier supplementation of infant diet than was previously the case became common in PNG. This has lead to general improvements in growth and nutritional status. However, in populations where undernutrition is still common, infection has become more important than primary malnutrition as the initiator of growth faltering due to undernutrition-infection interactions. PMID- 11216412 TI - Half-a-century of the "Kormend Growth Study". AB - The authors give a sketch about the "Kormend Growth Study" which is series of cross-sectional growth studies, carried out in Kormend, a small town in Western Hungary. The first investigation was carried out in 1958 (K-58) and it has been repeated every ten years (K-68, K-78, K-88, and K-98). All 3-18 year-old healthy boys and girls in nurseries and schools in Kormend were involved in the study. Twenty-three body measurements were taken. This paper focuses on changes in height, weight, and BMI. Means of these two body measurements show an increase from time to time (as a phenomenon of positive secular trend), however, the secular trend for increasing height and weight is declining. BMI follows a similar pattern. PMID- 11216413 TI - Empirical verification of the weighted system of criteria for the elite basketball players quality evaluation. AB - This article is a continuation of research aimed at formation of a system of criteria for the expert evaluation of the basketball players' actual quality. So far, the external standards for assessing players' performance have been defined and described and the relative importance coefficients of each criterion for the performance evaluation per positions in the game have been established as well. The purpose of this research was to test empirically the latter--the weighted system of criteria for evaluating the actual quality of basketball players proposed by Trninic and Dizdar (2000). Based on the determined descriptive indicators and the coefficients of importance of criteria, and on the degree of the objectivity level (interobservers' agreement) of the expert evaluations, it can be concluded that the measuring attributes (objectivity and sensitivity) for most of the criteria are in accordance with their relative importance coefficients for a particular position in the game. Consequently, the structure of the relevant criteria for each play position in the basketball is proposed. PMID- 11216414 TI - The influences of training on rowers of different age. AB - We measured 14 rowers and divided them into two groups according to age and years of training. Our goal has been to establish the influence of several years of programmed training on the structure of the body, oxygen carrying capacity and oxidation capacity of muscle cells, the chemical composition of blood and characteristics of pulse and lactate curves in rowers. As to the structure of the body, the two groups did not differ if we equalised them according to body height. Differences existed in the determinants of oxygen carrying capacity and oxidation capacity of muscle cells. Older rowers had lower pulse at rest, higher step test index, lower pulse immediately after the step test and in the last minute of the test on a bicycle ergometer and higher maximal oxygen pulse. While at rest, no significant differences between the groups were observed in most of the analysed substances in the blood serum. With the increase of age and training period an increase of the concentration of creatinin and activity of creatine kinase and lessening of the activity of alkaline phosphatase was noted. Length of training period lowers the levels of cholesterol and free fatty acids and increases the level of triglycerides in blood serum. An increase of the activity of creatine kinase and lactate dehydrogenase and the formation of a specific pattern of isoenzymes was observed. The pulse and lactate curve flattened and moved to the right. PMID- 11216415 TI - Terminal hinge axis--Hobo point--Frankfurt horizontal relations. AB - Aim of this investigation was to determine the spatial relations of the terminal hinge axis of the temporomandibular joints toward Frankfurt horizontal. The sample consisted of 50 examinees. Terminal hinge axis was located, using Lauritzen's technique, on the left side of face for each examinee. Arbitrary point, as proposed by Sumiya Hobo, was measured and point Orbital was defined by palpation. On designated points steel pellets 0.25 mm in diameter were stocked. Lathero--latheral cephalogram was obtained for each examinee. Cephalograms were traced down on a transparent foil and points Orbital, THA--terminal hinge axis, Hobo and Porion--as the uppermost point of the metal ear rod of the cephalostat, were designated. Connecting points Orbital and Porion, Frankfurt horizontal was defined, and shortest distance toward points THA and Hobo, as well as between them were measured. Lines parallel and perpendicular to Frankfurt horizontal were drawn through point THA. In a co-ordinate system defined in such a way, upper left quadrant was first, upper right second, lower right third, and lower left was fourth. Observation was made in which quadrant Hobo point was located. Measured values were statistically evaluated. Results revealed that Hobo point is located in first quadrant in 5 cases, in second in 7, third quadrant in 18, and in fourth in 20 cases. That means that Hobo point is located lower to the THA point in majority of our population. Points THA and Hobo were not identical in any case. Mean values of variables showed that investigated points were inferior to the FH. Measures of variability revealed great variability of both points toward FH, as well as for their mutual distance. It could be pointed out that THA point should be defined kinematically during prosthodontic procedures, and that orientation in articulator's space should not be according to the FH. PMID- 11216416 TI - The satisfaction with the removable partial denture therapy in the Croatian adult population. AB - Little is known about the outcomes of treatment and patient's satisfaction with removable partial dentures in adult Croatian population. Therefore patient's satisfaction with their partial dentures in relation to some socio-economic variables was studied. Patient's satisfaction with denture retention, speech, aesthetics, comfort of wearing dentures, chewing ability was also studied in relation to different denture classification, construction, material, denture base shape (major connectors), denture support and the number of missing teeth. A total of 165 patients, 59 males and 105 females between 38 and 87 years took part in this study. A questionnaire, devised for a purpose of the study, was divided into three parts. In the first part, patients answered questions about age, gender, marital status, education, general health, socio-economic status, self supporting life, period of tooth loss and number of previous denture experiences and in the second part, patients graded their partial dentures, depending on the level of satisfaction, by using a scale from 1 to 5. In the third part a dentist determined Kennedy classification and their modifications, denture material and denture support, denture base shape and the number of missing teeth and graded a denture construction. Influence of these factors on patient's satisfaction was analyzed. A majority of the examined patients were satisfied with the partial prosthesis, but a small amount of dissatisfaction existed. More then half of them scored all the examined parameters to the best score category. Considering chewing with lower partial dentures, women were more satisfied than men (p < 0.05). Patients with more missing teeth gave lower grades for the comfort of wearing dentures (p < 0.05). Patients of higher education gave lower grades (p < 0.05) for the aesthetics. Patients were not satisfied with speech if the dentist graded a construction of a lower partial denture low (p < 0.05). Dissatisfaction was related to mastication, aesthetics, number of missing teeth and ability of speech. These findings can aid a clinician in discussing a treatment plan and help a patient understand the risk of dissatisfaction in the presence of certain factors. PMID- 11216417 TI - Ten-year evaluation of conservative and surgical treatment of gingival recession. A case series study. AB - In the last years the treatment of non-inflammatory periodontal diseases has greatly changed. Apico-coronal dimension of gingival tissue is not considered to be of utmost importance, but significance of tissue thickness over each tooth is stressed. Purpose of this study was to show results of conservative and surgical treatment of gingival recession. Sample consisted of two groups of subjects, which have been treated in one of stated ways during ten years. The data was obtained on the beginning and after ten years of recall. Both groups showed increased dimension of keratinized gingiva during observed time with decrease of gingival recession, plaque- and gingival index. It is considered that treatment should start with conservative measures with necessary motivation of the patients. If it does not show improvement, one should consider best surgical method available for each patient. Clinical results show success in both groups, meaning that treatment was properly decided on. PMID- 11216418 TI - Effect of amine fluoride on enamel surface morphology. AB - In this in vitro study, examination of the enamel surface morphology after topical application of an amine fluoride solution with different fluoride (F) content was carried out. Sound human enamel slabs were treated with an amine fluoride solution containing either 1.0, 0.5 or 0.25% F for 3 min. during 3 days. All slabs were examined using scanning electron microscopy and energy-dispersive spectroscopy (SEM/EDS) qualitative analysis. The globular precipitates were revealed in all treated specimens, regardless of F content. The distribution of the deposits was more homogeneous in groups treated with higher concentrations; however, the globules were larger and more cubical in groups treated with lower fluoride concentrations. These larger globules could be less soluble and thus serve as a fluoride reservoir for a more extended period and so they could contribute to the caries preventive effect in professional topical products with lower fluoride concentration. Following the 24-hour treatment with KOH the precipitates could be removed; however, the enamel surfaces covered with the precipitates were less degraded than the untreated enamel. The EDS qualitative analysis showed that the intensities of fluoride signals were increased with the higher concentration of fluoride in an amine fluoride solution, while the intensities of calcium signals were decreased. The enamel surface precipitates were alkali-soluble, but we were not able to demonstrate that they are pure calcium fluoride. PMID- 11216419 TI - Interpopulation differences in acoustic characteristics of phonation. AB - The purpose of this study was to investigate possible differences in acoustic characteristics of phonation between populations of European and African origin. The subjects were 33 adult males divided in two groups. Group One consisted of 17 men of African origin, and Group Two included 16 men of European origin. All subjects were without vocal pathology at the time of the investigation, smokers and non-smokers. Sustained phonation of the vowel /a/ was acoustically analyzed by the Real-time Frequency Analyzer (Bruel and Kjaer, type 2123). Variables included f0, intensity of f0, intensity of harmonics 1-7, jitter and noise level intensity. One-way variance analysis showed statistically significant difference between the two groups in intensity of the second harmonic only. The same analysis has been repeated with non-smokers and showed statistically significant differences in intensities of the second and the third harmonic leading to assumption that there may be fine differences in vocal fold vibration between Group One and Group Two. Factor congruence analysis showed differences between samples in factor structures. It could be possible that these differences reflect psychoacoustic level. PMID- 11216420 TI - Femoral neck anteversion: values, development, measurement, common problems. AB - The femoral neck anteversion angle is an important factor for hip stability and normal walking. It is multifactoral result of evolution, heredity, fetal development, intrauterine position, and mechanical forces. Abnormal FNA sometimes can be associated with many clinical problems ranging from harmless intoeing gait in the early childhood, to disabling osteoarthritis of the hip and the knee in the adults. In most cases is associated with minor functional problems in children during growth, but cause a concern in parents for children future. The child must be examined carefully and an accurate diagnosis must be established. The most important part of care is observation of the children. If abnormal femoral neck anteversion produces severe functional disability, derotational osteotomy should be done, but delayed until late childhood. PMID- 11216421 TI - Morphological and biomechanical analysis of a skeleton from Roman imperial necropolis of Casalecchio di Reno (Bologna, Italy, II-III c. A. D.). A possible case of crutch use. AB - A Roman skeleton (T.130) from the roman necropolis of Casalecchio di Reno has been studied in order to understand if the hypothesis of crutch use, suggested by the severe articular degeneration at the hip joint that caused evident reduction of his locomotory possibilities, could be supported by the morphological alterations of other bones and joints. The pathological changes and muscular development of the upper limbs and shoulder girdle bones suggest that these parts were submitted to a great mechanical stress. The observations are consistent with the hypothesis of crutch use that would have involved a new weight-bearing function of the upper limbs in order to help locomotion, even though it is difficult to assess the number and type of the crutches. The comparison with other possible cases of crutch use reported in literature gives an additional support to the interpretation of the findings. PMID- 11216422 TI - Symbolism in prehistoric man. AB - The aptitude for symbolization, characteristic of man, is revealed not only in artistic representations and funerary practices. It is exhibited by every manifestation of human activity or representation of natural phenomena that assumes or refers to a meaning. We can recognize functional symbolism (tool making, habitative or food technology), social symbolism, (language and social communication) and spiritual symbolism (funerary practices and artistic expressions). On the basis of these concepts, research into symbolism in prehistoric man allows us to recognize forms of symbolism already in the manifestations of the most ancient humans, starting with Homo habilis (or rudolfensis). Toolmaking, social organization and organization of the territory are oriented toward survival and the life of the family group. They attest to symbolic behaviors and constitute symbolic systems by means of which man expresses himself, lives and transmits his symbolic world. The diverse forms of symbolism are discussed with reference to the different phases of prehistoric humanity. PMID- 11216423 TI - Initiation of healers in Ethiopia: a case study. AB - The aim of this study is to see how healers are initiated in Ethiopia. The paper also describes the position of traditional healers in the current situation of Ethiopia. It is found out that most of spiritual healers believed that they are selected by divine power or spirit. The selections are manifested by a single or a combination of ways namely: through dream, escaping mortal accident, and miraculous healing from chronic illnesses. However, secular healers got the initiation through apprenticeship. It is noted that in many cases "spirit selected healers" could also undergo apprenticeship. PMID- 11216424 TI - Genograms of exile and return families in Croatia--a medical anthropological approach. AB - This article presents the most important results of an applied anthropological long-term study of the prolonged exile and return that many families are currently undergoing in Croatia. The results are elaborated with a special reflection upon two important overlapping issues concerning the methodological approach that was applied: firstly, it discusses the crucial questions which motivated the search for a tool that will not distort the experiences, reality and suffering of exile families; and secondly, it critically describes the application of the genogram (a tool borrowed from systemic family therapy) in the exile setting. This tool was not only useful in the clinical sense of psychotherapeutically helping the families, but was also a very flexible part of the methodology orientated towards evoking family history and providing valid knowledge about different family and living circumstances. PMID- 11216425 TI - The impact of traumatic experience on attitude towards future in refugee adolescents. AB - Traumatic experience has overall far reaching consequences on personality. In particular, it has significant impact on teenagers that are just approaching the phase of solving their identity problems. This research examines the relation of traumatic experience and attitude towards the future in two groups of adolescents. The first group consists of 20 adolescents-refugees from the East Slavonia that were settled in Rijeka area with their parents during the last six years. The second group consists of 20 adolescent's local inhabitants that were influenced by the war only indirectly. Results show significant difference between refugees and non-refugees in expressed interpersonal trust, frustration tolerance, and formation of close contacts, adaptability, precaution, bitterness, and social desirability. Both groups show increased depression, pessimism and poor self-control. This might be considered as general characteristic of society in war. PMID- 11216426 TI - Adolescent development and external influences. AB - There are two different approaches to the definition of "normal" in adolescence: psychoanalytic interpretation and empirical research. They are not necessarily at odds but can complement each other if normalcy is viewed as a dependent variable. Its definition depends also on cultural rules, social values and expectancies, professional orientations, personality traits and political climate, which all determine the tolerance level for aberrance. The adolescent development including biological, cognitive and psychosocial changes is related to the existing social formations and processes. It is affected by family, peer groups, neighborhood, work and wider community. The paper describes the adolescent development in particular social contexts. PMID- 11216427 TI - Study on the ethical concepts of the Japanese writer Yukio Mishima, ultra nationalist. AB - After WWII, ultra-nationalism, which was the leading ideology of wartime Japan, seemed to have lost its power to inspire the Japanese. In the 1960s, when the Japanese began to enjoy economic prosperity, Yukio Mishima, deploring that the Japanese were losing the traditional spirit and morality of the nation, was one of those citizens who felt a strong nostalgia for wartime Japan. In an attempt to revive the spiritual exaltation of wartime Japan, Mishima took radical action as an ultra-nationalist, and killed himself by Hara-kiri. Mishima's ethical concepts, which center on the ethos of warriors who dedicate themselves to the defense of their commune, have structural similarities to the ethical structure of the Kanun, which may be called the ethics of "blood". Mishima's theory of ultra-nationalism has a paradoxical logic, which seems to be related to the ethical concepts of a society without state power. PMID- 11216428 TI - [Laparoscopy in differential internal medicine diagnosis]. AB - Diagnostic laparoscopy has still important implications in the differential diagnosis of numerous diseases despite the impact of non invasive imaging procedures. One of the most important indication, besides chronic liver diseases, is staging of malignancies. Laparoscopy improves considerably the predictability whether a distal carcinoma of the esophagus, or a stomach cancer or a pancreatic carcinoma can be resected. Laparoscopy is unbeaten in diagnosing peritoneal metastases. Thus, laparoscopy prevents unnecessary explorative laparotomies. Regarding tumor staging, a comparison is mandatory between minilaparoscopy, conventional laparoscopy in analgosedation performed by the gastroenterologist and laparoscopy in intubation anesthesia performed by the surgeon immediately before planned laparotomy. The significance of minilaparoscopy especially regarding chronic liver diseases and correct diagnosis of liver cirrhosis and hepatocellular carcinoma in cirrhosis will certainly increase. Laparoscopy remains to be an important diagnostic tool in diseases of unknown causes, i.e. fever of unknown origin. Laparoscopic sonography is the most sensitive method to detect small liver tumors, such as metastases or multilocular hepatocellular carcinoma. PMID- 11216429 TI - [Safety and value of minilaparoscopy in high risk patients]. AB - INTRODUCTION: Coagulopathies and thrombocytopenia may constitute contraindications for percutaneous liver biopsy. We investigated the safety and value of visually guided liver biopsy using minilaparoscopy in patients with coagulation disorders. PATIENTS AND METHODS: We studied 50 patients requiring a liver biopsy, but whose risk of severe bleeding complications was considered too high for the following reasons: INR > 1.5 (40%), platelets 50/nl (36%) or both (18%), other coagulopathies (6%). Indications for liver biopsy were: Hepatopathy of unknown etiology (38%), fulminant liver failure (18%), virus induced hepatitis (6%) and evaluation for liver transplantation (38%). Patients underwent minimally invasive diagnostic laparoscopy and liver biopsies were obtained with a Silverman or Menghini needle. Bleeding was stopped or prevented by coagulation with the argon beamer or a monopolar probe or application of fibrin glue. RESULTS: Macroscopical assessment of the liver was possible in all patients. A liver biopsy was performed in 47/50. 46/47 biopsy specimens were large enough to allow reliable histological evaluation. The diagnostic procedure had major therapeutic consequences in 35/40 patients. No relevant bleeding from the liver biopsy site occurred. CONCLUSION: We demonstrated that laparoscopically guided liver biopsy is safe even in patients with a very high risk of bleeding complications because of coagulation disorders. It is therefore an attractive and preferable alternative to transjugular liver biopsy. PMID- 11216430 TI - [Value of minilaparoscopy in comparison with conventional laparoscopy in diagnosis of liver diseases--intermediate term results of a prospective, randomized study]. AB - INTRODUCTION: Laparoscopy plays an essential role in the diagnosis of hepatic diseases. During the past few years, minilaparoscopy (ML) has increasingly emerged as an alternative diagnostic method in this field. We hereby present the preliminary results of a randomized trial comparing ML with conventional laparoscopy (CL). PATIENTS AND METHODS: 92 with suspected hepatic disease were randomized either to undergo CL (n = 47) or ML (n = 45). For CL, we used a Hopkins-laparoscope (O 11 mm, Storz, Tuttlingen) and ML was performed with a 1.9 mm small-diameter optic (Wolf, Knittlingen). RESULTS: Laparoscopy with simultaneous liver biopsy could successfully be performed in 88/92 patients. ML could be performed in a significantly shorter time than CL (25 vs. 28 min, p < 0.05). Liver cirrhosis was diagnosed by laparoscopy in a similar proportion of patients (70% in CL, 56% in ML). In 76% of cases, histology confirmed macroscopic signs of liver cirrhosis. Cirrhosis was found in one patient of each group solely by histologic examination of biopsy specimens. The number of bleeding complications during CL equaled the proportion of hemorrhagias in the ML-group. DISCUSSION: In the workup of hepatic disease, ML is a diagnostic tool comparable with CL. The fact that ML can be performed in significantly shorter time and seems subjectively less invasive might be an argument for a better acceptance by patients. PMID- 11216432 TI - Staging laparoscopy for gastrointestinal malignancies: current indications. PMID- 11216431 TI - [Laparoscopic tumor staging in gastrointestinal carcinomas: significance of internal medicine laparoscopy]. AB - This study was performed to assess the role of additional diagnostic laparoscopy in the preoperative staging of patients with gastric cancer and pancreatic cancer prior to intended curative surgery. Furthermore patients with ascites of unknown origin were evaluated. 127 patients with primary solid abdominal tumors were eligible for evaluation; of those 66 patients had a gastric cancer and 61 a pancreatic cancer. Patients without histologically proven metastases proceeded to laparotomy. Ascites of unknown origin was the indication for performing a diagnostic laparoscopy in 23 patients. Metastases were detectable laparoscopically in 13 of 66 patients (20%) with gastric cancer. Intraoperatively metastases were evident in further 7 cases. In 14 of 61 patients (23%) with pancreatic cancer metastases were detected by laparoscopy and in further 5 patients intraoperatively. A peritoneal carcinosis was diagnosed laparoscopically in 17 of 23 patients with ascites of unknown origin. Preoperative staging by additional diagnostic laparoscopy proved effective in patients with gastric- and pancreatic cancer. PMID- 11216433 TI - [Staging laparoscopy with laparoscopic ultrasound--indications and value in the surgical oncological therapy concept]. PMID- 11216434 TI - [Significance of staging laparoscopy in pancreatic carcinoma: a case report]. AB - Accurate staging of pancreatic malignancy is essential to properly plan appropriate therapy. The purpose of preoperative staging of intraabdominal malignancies is to identify patients in whom malignancies are unresectable and therefore would not be candidates for curative surgery. Routine preoperative evaluation of intraabdominal malignancies typically include abdominal helical computed tomographic (CT) scanning and/or ultrafast magnetic resonance (MR) imaging. In fact both investigations are considered mandatory for intraabdominal malignancies. But despite modern techniques a significant number of false negative results occur (more than 20%). This has led to the investigation of additional staging modalities to better identify patients with unresectable disease. In this purpose we present the case of a patient with pancreatic carcinoma. After preoperative imaging (ultrasound, endosonography and MRI) there was no evidence for metastatic disease (uT3uN1). He underwent laparoscopy and a hepatic lesion was detected, histologically consistent with a liver metastasis. In this patient an unnecessary laparotomy could be avoided. In conclusion laparoscopy is an important tool in the staging of intraabdominal malignancy for patients with locally advanced disease without signs of tumor spread in CT or MRT. It is a relatively simple, well-tolerated and safe procedure and decreases the rate of unnecessary laparotomies. It should be considered in all patients with pancreatic malignancy in whom laparotomy is planned, either to establish the diagnosis or before an attempt at curative resection. PMID- 11216435 TI - What is the future of laparoscopy and can we do without it? PMID- 11216436 TI - [Minilaparoscopy in liver diagnosis--an advantage?]. PMID- 11216437 TI - Performance-based home care for the elderly: the quality of circumstance protocol. AB - The paper introduces a performance-based protocol for use by case managers in home care programs for the elderly. Drawing upon the goal attainment approach to service planning and evaluation, the protocol specifies a set of five observable conditions ranging from the highly desirable to the highly undesirable that correspond to each ADL and IADL dimension plus five other dimensions of importance to community residing frail elders. The conditions documented through the protocol provide a basis for setting explicit expectations of what can be achieved through home care interventions. The paper describes a pilot effort to test the protocol in the Massachusetts state funded home care program. Both the protocol's client assessment form and data collection guide are included as appendices. PMID- 11216438 TI - Additional psychometric evaluation of the Outcomes and Assessment Information Set (OASIS). AB - The OASIS represents a rich opportunity for researchers interested in home health care outcomes. However, little psychometric information has been published. The purpose of this study was to provide additional psychometric data for selected portions of the OASIS using a sub-set of 201 subjects from a previously published study. Conceptual domains were identified-functional, affect, behavioral and clinical. Reliability was evaluated using Cronbach's alpha and the kappa coefficient for intra-rater reliability. Construct validity was evaluated by principal axis factor analysis within each domain. The functional domain had the best reliability and validity. The affect and behavioral domains had adequate kappa scores, but the alphas and the factor analyses were problematic. Two of the clinical items did not perform well with kappa scores. Recommendations and suggestions for use of the OASIS are made. PMID- 11216439 TI - Balancing resources and risk: selecting home care clients in Florida's CARES program. AB - Selecting home care patients who would otherwise go into a nursing home always involves error: serving too many or two few. To clarify the choices program and case managers must make, we propose a risk-based alternative to current selection methods that involves scientifically-derived variable weighting and conscious choice of cut-off score for bestowing home care eligibility. We illustrate our proposal with data from Florida's Comprehensive Assessment and Review of Long term Care Services (CARES) program. Using logistic regression we identify characteristics that distinguish clients recommended for nursing home placement from those referred to the community and use these results to estimate the risk of nursing home recommendation for each client. An approach to using these risk scores to determine eligibility is demonstrated along with assessment of the impact of alternative risk score cut-offs on denying care to as many as half or as few as 5% of clients served. PMID- 11216440 TI - State Medicaid home health licensing and certification. AB - This study collected and analyzed data on the number of licensed and certified home health care agencies and licensed home care/personal care agencies in the US. The study also examined the state laws and regulations pertaining to Medicaid home health agency requirements. There were 14,045 licensed home health agencies and 801 other licensed home care or personal care agencies in the US, but only 59 percent of these agencies were certified in 1998. The percent of certified agencies ranged from 22 percent in Maryland to 100 percent in ten states that only allowed certified agencies to provide home care. There was a wide range in the number of agencies in states with the average being 6.1 agencies per 100,000 population. The 41 states with state licensing of home health agencies had a wide range of policies but most were more lenient than the federal Medicare certification requirements. PMID- 11216441 TI - The bible: truth or legend, fact or fantasy? PMID- 11216442 TI - Resistance to Antimicrobial Agents. Proceedings of a meeting. Monte Carlo, Monaco, 20-23 October 1999. PMID- 11216443 TI - [59th Annual Meeting of the Japanese Cancer Association. Yokohama, October 4-6, 2000. Abstracts]. PMID- 11216445 TI - 5-HT receptors mediating external carotid vasoconstriction in vagosympathectomized dogs. AB - One specific example reflecting the complexity of cardiovascular responses induced by serotonin (5-hydroxytryptamine; 5-HT) and the progress achieved in the pharmacological characterization of the receptors involved can be illustrated by the effects of 5-HT on the canine external carotid artery bed. Within this framework, it has been shown that the external carotid vasoconstrictor response to 5-HT in the dog is mediated by '5-HT1-like' receptors, which being blocked by the 5-HT1B/1D receptor antagonist GR127935, resemble 5-HT1B/1D (previously called 5-HT1D beta/1D alpha) receptors. It was proposed that these receptors could belong to the 5-HT1B, rather than the 5-HT1D, subtype on the basis of their resistance to blockade by a high dose of ritanserin (a potential 5-HT1D receptor antagonist) and the presence of mRNA for 5-HT1B(5-HT1D beta) receptors, but not for 5-HT1D(5-HT1D alpha) receptors, in vascular smooth muscle. With the advent of subtype-selective antagonists it was subsequently shown that external carotid vasoconstriction to 5-HT and sumatriptan is dose-dependently antagonized by the selective 5-HT1B receptor antagonist SB224289 (2,3,6,7-tetrahydro-1'-methyl-5-[2' methyl-4' (5-methyl-1,2,4-oxadiazol-3-yl) biphenyl-4-carbonyl] furo [2,3-f] indole-3-spiro-4'-piperidine hydrochloride), whereas the selective 5-HT1D receptor antagonist BRL15572 (1-(3-chlorophenyl)-4-[3,3-diphenyl (2-(S,R) hydroxypropanyl) piperazine] hydrochloride) was ineffective. These findings represent the first in vivo evidence showing that vascular constriction induced by 5-HT and sumatriptan is mediated primarily via 5-HT1B, but not 5-HT1D receptors. The pharmacological profile of these receptors could be similar (isolated human temporal artery and porcine carotid arteriovenous anastomoses) to other putative 5-HT1B receptors mediating vasoconstrictor responses. In view of the putative pathophysiologic role of external carotid (and extracerebral) vasodilation in migraine, the constriction of these blood vessels by sumatriptan via 5-HT1B receptors may be, at least partly, responsible for its therapeutic efficacy in migraine. PMID- 11216446 TI - CB1 receptor localization in rat spinal cord and roots, dorsal root ganglion, and peripheral nerve. AB - AIM: The localization of CB1 receptors in the spinal cord, spinal roots, dorsal root ganglion (DRG), and peripheral nerve of the rat was determined. METHODS: We studied the distribution of CB1 cannabinoid receptors by immunohistochemistry using an antibody raised against the N-terminal of the receptor. RESULTS: The spinal cord showed numerous transverse fibers labelled for CB1 receptors throughout and concentrated in the dorsal horn. Lightly-stained cells were observed throughout the spinal cord gray matter. The DRG also showed cells and fibers labelled for CB1 receptors. Labelled fibers were observed in both dorsal and ventral roots as well as in peripheral nerves. CONCLUSION: The presence of CB1 receptors in the DRG, the dorsal root, and the dorsal horn is in accordance with the analgesic effects of cannabinoids. The presence of labelled cells and fibers in the ventral horn and ventral root provides a substrate for cannabinoid induced muscle relaxant and antispastic effects. PMID- 11216447 TI - Dopaminergic system does not play a major role in the precipitated cannabinoid withdrawal syndrome. AB - AIM: To determine the dopaminergic system involvement in precipitated cannabinoid withdrawal syndrome. METHODS: The dopamine D1 receptor antagonist SCH23390 or the dopamine D2 receptor antagonist sulpiride was administered to rats chronically treated with either delta 9-tetrahydrocannabinol (THC) or vehicle. Subjects were then injected with either SR141716A or vehicle and behavior was observed for 1 h. RESULTS: Administration of the cannabinoid receptor antagonist SR141716A to animals chronically treated with THC as described by Tsou et al (1995) produced a profound withdrawal syndrome. Treatment with dopamine antagonists did not attenuate cannabinoid precipitated withdrawal syndrome in THC tolerant animals while the agonists increased the syndrome. CONCLUSION: It is unlikely that the dopaminergic system plays a major role in mediating the behavioral aspects of the cannabinoid withdrawal syndrome. PMID- 11216449 TI - Analysis of antibodies raised against soluble and membrane bound proteins of Nosema grylli (Microspora) spores. AB - Microsporidia (M), representatives of the phylum Microspora, make a world-wide distributed group of intracellular protists, parasitic in the vast number of hosts, from Protozoa to Primates. In their morpho-functional organization, both very primitive and extremely specialized features are seen definitely combined. Data available on RNA and DNA sequences suggest that M may be the most ancient eukaryotes. By the present, as many as 13 microsporidian species have been recognized as opportunistic pathogens in AIDS and transplant patients. Information about structural, transport and regulatory proteins of M, as well as on their enzymes is scarce, though it could serve as a basis for understanding pathogenicity of M and indicate some possible sites of relevant suppressive therapy. The present study persuaded two main goals: 1) to examine two ways of antigen preparation (from the infected organ and from the purified spores) and to evaluate their relation to the yield of the resulting antibodies; 2) to identify and localize new proteins with the help of the obtained antibodies by means of IFA, IEM and WB. Mice were immunized: 1) with dissolved proteins of heavily loaded with parasites fat bodies isolated from crickets Gryllus bimaculatus infected with Nosema grylli, and 2) with proteins of the purified spores of N. grylli. As a result two antisera were obtained. Antiserum 1 reacted predominantly with spore walls on IFA slides and ultrathin sections (IEM). It also reacted with a broad spectrum of parasite and host cell proteins on WB. Antiserum 2 recognized polar filaments and walls of discharged spores in IFA and IEM tests. It did not react with undischarged spores or fat bodies of uninfected crickets and gave a comparatively weak reaction with those of the infected hosts. Hybridization of spleen cells of immune mice with murine myeloma cells resulted in several hybridoma clones. They produced Mabs, 5 of which were tested by IFA, IEM and WB. Mab 1BF3 recognized 55 kDa protein connected with polar filaments as it was clearly suggested by IEM and IFA. Mab 1BD9 recognized 25, 34, 43 kDa proteins from the fraction of membrane bound proteins of spore walls, the sites of their interaction with antigens being marked with uneven fluorescence (IFA) and by gold precipitates on spore walls (IEM). Mab 1BB9 reacted with 36, 45, 65 and 75 kDa proteins, which belong mainly to the fraction of membrane-bound spore proteins, and gave a weak fluorescence associated with spores. Mab 2AB3 recognized 44 and 60 kDa proteins from the fraction of soluble spore proteins, and Mab 2AD4 acknowledged a single protein of 55 kDa from the same fraction. The obtained antibodies add to the existing microsporidian antibody bank and can be used for further work of isolation, description and sequencing the microsporidian proteins in order to understand eventually their functions. PMID- 11216448 TI - Intrathecal cannabinoid administration suppresses noxious stimulus-evoked Fos protein-like immunoreactivity in rat spinal cord: comparison with morphine. AB - AIM: To determine whether cannabinoids suppress noxious stimulus-evoked Fos protein-like immunoreactivity (FLI) through direct actions at the spinal level. METHODS: Rats were implanted with intrathecal (ith) catheters at least one week prior to evaluation in the formalin test. Effects of the cannabinoid agonist, CP55,940 (80 micrograms ith) on formalin pain and FLI in rat spinal cord were compared with that of the prototypic narcotic analgesic, morphine (20 micrograms ith). CP55,940 suppressed pain behavior and FLI induced by intraplantar formalin. The cannabinoid suppressed Fos in the neck region of the dorsal horn and in the ventral horn, but not in the nucleus proprius. The efficacy of the cannabinoid in suppressing FLI in these laminae and pain behavior was comparable to morphine administered via the same route. However, only morphine suppressed FLI in the superficial dorsal horn relative to vehicle treatment. CONCLUSION: Cannabinoids suppress nociceptive processing, in part, through actions at the spinal level. However, morphine showed greater potency and efficacy than CP55,940 in suppressing formalin-induced FLI following spinal administration. PMID- 11216450 TI - Proceedings of the 17th International Pigment Cell Conference. Nagoya, Japan. October 30-November 3, 1999. PMID- 11216451 TI - [Proceedings of a symposium on the kidney and lipids. Grenoble, France, 16-17 April 1999]. PMID- 11216452 TI - Reporting of occupational and environmental research: use and misuse of statistical and epidemiological methods. PMID- 11216454 TI - Air pollution research databases. PMID- 11216453 TI - Occupational exposures and pancreatic cancer: a meta-analysis. PMID- 11216455 TI - [Vascular tunnel creation to improve the effect of decompressive craniectomy in severe traumatic cerebral edema]. AB - More than million people/year die after head injury. The cause of death in 50% is the secondary brain swelling with incuneation. Today decompressive craniectomy with durotomy for traumatic brain swelling is performed as second--tier therapy at many clinics and hospitals. The literature mentions this method only as an option. The problem so far existed in the following fact: although the above mentioned method successfully diminished the ICP still despite this result, partial or total lesion occurred in the herniated part of the brain. The actual cause of these symptoms is found in the blockage of the veins and arteries, caused by shearing and compressive forces between the dural edge and brain tissue. Venous congestion induces further edema in the protruding parts of the brain, thus causing lesion by strangulated necrosis and hypoxia. The new surgical technique consists of a stellate manner durotomy and of creating a vascular tunnel by supporting pilasters made of haemostatic sponge around the main cortical veins and arteries of herniated brain. With the help of new technique the authors managed not only to reduce the intracranial pressure significantly but they could avoid further edema and vascular lesion as well. This due to the fact that with this method we assure the blood circulation and venous drainage of the herniated part of the brain. We think, that in this case despite of the initially severe status, the properly indicated combination of craniectomy, durotomy and vascular tunnel creation, could be the main factor of the surprisingly favorable outcome. PMID- 11216456 TI - [[In vitro culture of iris cells]. AB - BACKGROUND: The biological behaviour of iris cells in vitro was not yet completely investigated. For a more detailed study of the scope of cultivation of iris cells in vitro we isolated human iris pigment epithelium (IPE) cells and iris fibroblasts. MATERIALS AND METHODS: For the purpose of this study iris cells were isolated from 19 donor eyes. A method was established for isolation and cultivation of IPE cells by means of fibronectin coating and the use of a special cell culture medium. Additionally, a method was developed for the selection of fibroblasts from iris stroma (IS) in vitro by means of fibronectin coating, passaging and proliferation in cell culture medium. RESULTS: The IPE and IS cells could be cultivated successfully. The IPE cells started to divide after a mean interval of 5.4 +/- 0.7 days in culture. The mitosis of IS cells was observed after 3.3 +/- 0.87 days in culture. Confluency of IPE cells was reached after 14.7 +/- 4.92 days and by IS cells after 8.1 +/- 1.45 days. Immunocytochemical staining using two antibodies for cytoceratin and one for human fibroblast showed that the IPE cell culture was pure and that the IS culture consisted of fibroblasts. Furthermore, electron microscopy of IPE and IS cultures confirmed the results of the immunocytochemical staining. CONCLUSIONS: The use of human IS and IPE cells in vitro has established a novel model for the research on iris cells. The model might possibly be applied in the research of metabolic structures and diseases of the iris. PMID- 11216457 TI - Early establishment of epithelial apoptosis in the developing human small intestine. AB - In the adult small intestine, the dynamic renewal of the epithelium is characterized by a sequence of cell production in the crypts, cell maturation and cell migration to the tip of villi, where apoptosis is undertaken. Little is known about enterocytic apoptosis during development. In man, intestinal architectural features and functions are acquired largely by mid-gestation (18-20 wks); the question whether the establishment of enterocytic apoptotic processes parallels or not the acquisition of other intestinal functional features remains open. In the present study, we approached this question by examining enterocytic apoptosis during development of the human jejunum (9-20 wks gestation), using the ISEL (in situ terminal uridine deoxynucleotidyl nick-end labelling) method. Between 9 and 17 wks, apoptotic enterocytes were not evidenced. However, beginning at the 18 wks stage, ISEL-positive enterocytes were regularly observed at the tip of villi. Since the Bcl-2 family of proteins constitutes a critical checkpoint in apoptosis, acting upstream of the apoptotic machinery, we investigated the expression of six Bcl-2 homologs (Bcl-2, Bcl-X(L), Mcl-1, Bax, Bak, Bad) and one non-homologous associated molecule (Bag-1). By immunofluorescence, we found that all homologs analyzed were expressed by enterocytes between 9 and 20 wks. However, Bcl-2 homologs underwent a gradual compartmentalization of epithelial expression along the maturing crypt-villus axis, to establish gradients of expression by 18-20 wks. Western blot analyses indicated that the expression levels of Bcl-2 homologs were modulated during morphogenesis of the crypt-villus axis, in parallel to their gradual compartmentalization of expression. Altogether, these data suggest that regulatory mechanisms of human enterocytic apoptosis become established by mid gestation (18-20 wks) and coincide with the maturation of the crypt-villus axis of cell proliferation, differentiation and renewal. PMID- 11216458 TI - Mental health, health, and education staff working together in schools. AB - The movement to develop expanded school mental health programs is still in its early stages. For child and adolescent psychiatrists to become involved and effective means negotiating a culture that is novel for many schools and forming and maintaining relationships with diverse staff in mental health, health, and education. PMID- 11216459 TI - Complexes between double-stranded DNA and chitosan can form cholesteric liquid crystalline dispersions. PMID- 11216460 TI - Acceleration of the recombination reaction between photooxidized bacteriochlorophyll and reduced primary quinone in reaction centers of Rhodobacter sphaeroides at T > 300 K. PMID- 11216461 TI - What osteopathists stand for in legislation. 1910. PMID- 11216462 TI - The future in retrospect. 1935. PMID- 11216463 TI - Tendencies in a social, political, and governmental way which may influence doctors. 1937. PMID- 11216464 TI - [Problems of child sexual abuse in Africa or the imbroglio of a double paradox: the example of Cameroon]. AB - OBJECTIVE: This study has investigated the prevalence of sexual abuse cases in Cameroon (Africa) and approached the way these cases are solved. METHOD: 405 medical certificates have been reviewed within a three years period. RESULTS: Over 405 medical certificates, 19 cases of sexual abuse have been identified. All the victims were girls. The great majority of them were aged 10-14 (57.9%) and 15 19 (31.6%). The sexual assaults have been perpetrated out of the family. CONCLUSION: The results show evidence of sexual abuse cases in Africa. Friendly adjustments by private contracts and family interventions with financial amends for the parents of the victims are often preferred to the court of justice, because of poverty, cultural pressures and judicial injunctions. PMID- 11216465 TI - Intermittent facial swelling. PMID- 11216466 TI - 30th Annual Meeting of the AADR (American Association for Dental Research) and the 25th Annual Meeting of the CADR. March 7-10, 2001. Chicago, Illinois, USA. Abstracts. PMID- 11216467 TI - 50th Annual Scientific Session of the American College of Cardiology. Orlando, Florida, USA. March 18-21, 2001. PMID- 11216468 TI - Approach to the patient with unexplained chest pain. AB - Patients with unexplained or noncardiac chest pain continue to present a difficult challenge to the gastroenterologist. Cardiac disease must be ruled out first as the history will not distinguish between coronary artery disease and other causes of substernal chest pain. A systematic approach to evaluation should include reassurance that the heart is normal and attempts to confirm an esophageal etiology. Gastroesophageal reflux disease is the most common esophageal abnormality associated with unexplained chest pain and may be identified by an aggressive trial of anti-reflux therapy or an abnormal prolonged ambulatory pH monitoring study. Endoscopy is almost always normal and of less use in this population than in those with heartburn as the presenting symptom. Judicious use of manometry with provocative testing to evaluate for esophageal motility abnormalities or esophageal sensitivity allows for optimal evaluation of those who do not have gastroesophageal reflux disease. This article reviews the clinical presentation, differential diagnosis, and approach to evaluation and therapy of this complex group of patients. PMID- 11216469 TI - Chemopreventive effects of coffee bean and rice constituents on colorectal carcinogenesis. AB - Polyphenolic compound chlorogenic acid (CGA) known to be much contained in coffee beans was found to have a regressive effect on induced aberrant crypt foci (ACF) as well as on development of ACF in azoxymethane (AOM)-induced colorectal carcinogenesis in rats. Rice germ and gamma-aminobutyric acid-enriched defatted rice germ inhibited AOM-induced ACF formation and colorectal carcinogenesis in rats. Ferulic acid (FA) also known to be contained in coffee beans and rice prevented AOM-induced ACF formation and intestinal carcinogenesis in rats. Both of food factors, coffee and rice may be of benefit to prevention of human colorectal cancers. PMID- 11216470 TI - Inhibitory effects of curcumin and capsaicin on phorbol ester-induced activation of eukaryotic transcription factors, NF-kappaB and AP-1. AB - Recently, considerable attention has been focused on identifying dietary and medicinal phytochemicals that can inhibit, retard or reverse the multi-stage carcinogenesis. Spices and herbs contain phenolic substances with potent antioxidative and chemopreventive properties. Curcumin, a yellow colouring agent from turmeric and capsaicin, a pungent principle of red pepper exhibit profound anticarcinogenic and antimutagenic activities. Two well-defined eukaryotic transcription factors, nuclear factor-kappa B (NF-kappaB) and activator protein 1 (AP-1) have been implicated in pathogenesis of many human diseases including cancer. These transcription factors are known to be activated by a wide array of external stimuli, such as tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), tumor necrosis factor, reactive oxygen species, bacterial lipopolysaccharide, and ultraviolet. In the present study, we found that topical application of TPA onto dorsal skin of female ICR mice resulted in marked activation of epidermal NF-kappaB and AP-1. Curcumin and capsaicin, when topically applied prior to TPA, significantly attenuated TPA-induced activation of each transcription factor in mouse skin. Likewise, both compounds inhibited NF kappaB and AP-1 activation in cultured human promyelocytic leukemia (HL-60) cells stimulated with TPA. Based on these findings, it is likely that curcumin and capsaicin exert anti-tumor promotional effects through suppression of the tumor promoter-induced activation of transcription factors, NF-kappaB and AP-1. PMID- 11216471 TI - Role of antimutagens/anticarcinogens in cancer prevention. AB - Recently it has become increasingly clear that chemicals found in our foods and beverages can prevent the genetic damage that leads to cancer initiation. Such substances may also affect subsequent events in the pathways that lead to cancer, and may have the potential to inhibit the mutations that allow tumor cells to become resistant to antitumor agents. We describe here the antimutagenic potential of Glabrene analogs against EMS-induced mutations utilizing modified Ames tests in S. typhimurium TA 100 and E. coli JC 5088. Results of studies of the ability of well-known antioxidants such as EGCG and related compounds to prevent drug resistance mutations in microorganisms are described, and their possible significance in the prevention of chemotherapeutic drug-resistance in tumor cells is discussed. PMID- 11216472 TI - Prevention of the formation of mutagenic and/or carcinogenic heterocyclic amines by food factors. AB - Introduction of phenolic antioxidants, thiol compounds and reductones into the heated model system composed of glucose/glycine/creatinine was effective to scavenge the intermediary pyrazine cation radical and to reduce the mutagenicity due to imidazoquinoxaline heterocyclic amines. Addition of a reductone, ascorbate or erythorbate, at 0.3% to ground beef effectively reduced the mutagenicity of cooked hamburger. Mutagenicity of cooked hamburger was also decreased by addition of glucose at more than 0.7% to ground beef. PMID- 11216473 TI - COX-2 and iNOS, good targets for chemoprevention of colon cancer. AB - Cyclooxygenase (COX)-2 has been suggested to play an important role in colon carcinogenesis. We found that the COX-2 selective inhibitor, nimesulide, reduces azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rats and colon carcinogenesis in mice, as well as formation of intestinal polyps in Min mice. Thus, selective inhibitors of COX-2, which catalyzes the synthesis of prostanoids, could be good candidates as chemopreventive agents against colon cancer. Examination of the effect of prostanoid receptor deficiency and a selective antagonist of prostanoid receptor on the development of AOM-induced ACF in mice revealed the involvement of the EP1 receptor. Moreover, a selective EP1 antagonist reduced the number of intestinal polyps in Min mice. These results suggest that PGE2 contributes to colon carcinogenesis through binding to the EP1 receptor. Nitric oxide synthase (NOS) is known to be overexpressed in colon cancers of humans and rats, and a NOS inhibitor, L-NG-nitroarginine methyl ester, was found to inhibit the development of AOM-induced ACF in rats. Thus, NOS including iNOS could also be a good target for chemoprevention of colon cancer, as in the COX-2 case. PMID- 11216474 TI - Functional food science in Japan: state of the art. AB - In 1984, a new science related to functional food was initiated by a National Project team under the auspices of the Japan Ministry of Education and Science. It was followed by a great many academic and industrial studies to occupy a central position in the field of food and nutritional sciences. In 1993, the Ministry of Health and Welfare established a policy of "Foods for Specified Health Uses" (FOSHU) by which health claims of some selected functional foods are legally permitted. Up to now (November 22. 1999), 167 FOSHU products have been born. Since the time (1984) when the concept of functional food" was proposed, it seems that the science in Japan has been progressing along, among others, a unique path of development. The uniqueness is seen in the development of functional foods by minimizing undesirable as well as maximizing desirable food factors. Hypoallergenic foods, developed from their materials by removing allergens, offer a good example. Another characteristic may be found in the field of sensory science which aims at elucidating a molecular logic of the senses of taste and smell in reference to their effects on physiological systems in the body. The paper discusses some characteristics of functional food science in Japan, with special emphasis on these topics. PMID- 11216475 TI - Effects of L-lysine deficient diet on the hypothalamic interstitial norepinephrine and diet-induced thermogenesis in rats in vivo. AB - Rats readily recognize an amino acid deficient diet, presumably via central mechanisms that involve hypothalamic circuits. Presently, effects of the essential amino acid L-lysine deficiency on the ventromedial (VMH) and lateral (LH) hypothalamus norepinephrine (NE) release were evaluated in free moving rats. Microdialysis measurement was undertaken once in 48 h (12:00 noon-14:00) in rats that had free access to food and drink. Significant decline in the food intake and VMH NE release were found in rats fed L-lysine diet. No changes were identified in LH NE release. Additionally, no significant differences in diet induced spatial thermogenesis between normal and L-lysine deficient non-stressed rats were found in vivo. The results suggested that the VMH NE release was specifically involved in the integration of signals about amino acid deficiency. However, the decrease in VMH NE was not translated into changes of thermogenic responses to diet. PMID- 11216477 TI - Protein hydrolysates for oral tolerance. AB - To induce oral tolerance in multiple sclerosis treatment, we proposed to use the predigested protein of pig spinal cord. The most biologically active composition was obtained from the hydrolysis of an undenaturated homogenate of proteins digested with pepsin. Feeding the rats with our preparation, before or after immunization with MS antigens, strongly reduced development of the experimental autoimmune encephalomyelitis (EAE). The biological results obtained in animals suggest that the developed method of induction of the oral tolerance should be effective in human treatment, at least as a support mechanism in combination with other treatment methods. PMID- 11216476 TI - Bioactive peptides derived from food proteins preventing lifestyle-related diseases. AB - Many kinds of bioactive peptides which might prevent lifestyle-related diseases are released from food proteins after enzymatic digestion. Inhibitory peptides for angiotensin I-converting enzyme (ACE) having anti-hypertensive effect have been isolated from enzymatic digests of various food proteins. LKPNM, which was isolated from the thermolysin digest of dried bonito was activated 8-fold by ACE itself and showed a prolonged effect after oral administration. Two vasorelaxing peptides, ovokinin and ovokinin(2-7), showing antihypertensive effect after oral administration were obtained from ovalbumin digests. We found that low molecular weight peptides derived from food proteins lowered serum cholesterol without increasing excretion of cholesterol and bile acids. An immunostimulating peptide isolated from an enzymatic digest of soybean protein prevented alopecia induced by cancer chemotherapy. PMID- 11216478 TI - Anticancer activity of hydrophobic peptides from soy proteins. AB - An anticancer peptide from soy protein was purified and isolated. Defatted soy protein was hydrolyzed with thermoase and hydrophobic peptides were extracted with ethanol. The peptide extract was fractionated by XAD-2 hydrophobic, gel filtration chromatography, and different C18 HPLCs. Anticancer activity of each fraction was assayed by measuring in vitro cytotoxicity on P388D1, a mouse monocyte macrophage cell line. IC50 value of a peptide fraction from Sephadex G 25 chromatography was 0.16 mg/ml. This peptide fraction at 1 mg/ml significantly affected cell cycle progression by arresting P388D1 at G2/M phases. Finally purified peptide from analytical C18 HPLC was nonapeptide of which molecular weight was 1157 Da and the sequence was X-Met-Leu-Pro-Ser-Tye-Ser-Pro-Tyr. PMID- 11216480 TI - Development of functional foods based on physiological activity of amino acids and peptides in Japan. PMID- 11216479 TI - Antitumor protein (AP) from a mushroom induced apoptosis to transformed human keratinocyte by controlling the status of prb, c-MYC, cyclin E-cdk2, and p21WAF1 in the G1/S transition. AB - Antitumor protein (AP) from a mushroom, induced the morphological changes typical to apoptosis such as nuclear condensation, aneuploidity, and DNA fragmentation at concentrations as low as 5-20 ng/ml to cancer cells. Molecular alterations related to cell cycle. Molecular alterations related to cell cycle, especially G1/S transition were investigated with a human keratinocyte transformed with oncoproteins, E6 and E7 of human pappiloma virus(HPV)-16. AP didn't alter significantly and oncosuppressor p53 level, but induced hyperphosphorylation of pRb. Time-dependent change of G1 cyclins, cdk2 and cdk4 after addition of AP showed that expression level of cdk inhibitors, INK4 family, and p27KIP1 did not altered, while that of p21WAF1 was downregulated. PMID- 11216481 TI - Respective bioavailability of quercetin aglycone and its glycosides in a rat model. AB - A large number of flavonoids, mostly O-glycosides, are found in foods of plant origin. The bound sugar moiety is known to influence their bioavailability. We examined here the effect of the nature of the sugar on the absorption of the glycosides. Four groups of rats (n = 6) received a meal containing 20 mg of quercetin equivalents supplied as aglycone, quercetin 3-glucoside, quercetin 3 rhamnoside or rutin. Plasma were hydrolysed by a beta-glucuronidase/sulfatase and analyzed by HPLC coupled to UV detection at 370 nm. Four hours after the beginning of the meal, the quercetin metabolites present in plasma were identical in all groups but their total concentrations were quite different. With pure quercetin the circulating levels were 1.7 +/- 1.8 microM, but this level was three fold higher when quercetin was supplied as quercetin 3-glucoside (33.2 +/- 3.5 microM). By contrast, the plasma concentrations of quercetin metabolites was quite low with the rutin meal (about 3 microM) and undetectable after the quercetin 3-rhamnoside meal. These data suggest that the 3-O-glucosylation improves the absorption of quercetin in the small intestine, whereas the binding of a rhamnose or of a glucose-rhamnose moiety to the aglycone markedly depressed its absorption. Additionnal experiments have shown that the higher plasma levels measured after the meal containing quercetin 3-glucoside compared to quercetin were maintained throughout a 24 hour period following the meal. In conclusion, the nature of the glycosylation markedly influences the efficiency of quercetin absorption in rats. Quercetin 3-glucose can be absorbed in the small intestine and is better absorbed than quercetin itself. By contrast, glycosides containing a rhamnose moiety could not be absorbed in the small intestine. PMID- 11216482 TI - Effects of food factors on signal transduction pathways. AB - Consumption of plant-derived foods, especially fruits and vegetables, has been linked to decreased risk of cancer. Laboratory studies with animals and cells in culture have shown cancer preventive activity of chemicals isolated from soy, tea, rice and many green, yellow and orange fruits and vegetables. Using cell culture, transgenic mice and knockout mice models to examine the anti-cancer effects of these dietary factors at the molecular level, we found that (11) (-) epigallocatechin gallate (EGCG), the major active polyphenol in green tea, and theaflavins, the major active components in black tea, inhibit epidermal growth factor (EGF)- or 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced JB6 cell transformation. At the same dose range that inhibited cell transformation, EGCG and theaflavins inhibited activator protein-1 (AP-1) activation. These compounds also inhibited ultraviolet B (UVB)-induced AP-1 and nuclear factor kappa B (NFkappaB)-dependent transcriptional activation; (2) resveratrol, found at high levels in grapes, inhibited cell transformation through the induction of apoptosis, mediated through JNK and p53-dependent pathways; (3) inositol hexaphosphate (InsP6), an active compound from rice and other grains, inhibited TPA- or EGF-induced transformation and signal transduction through its effects on phosphatidylinositol-3 kinase (PI-3) kinase; (4) phenethyl isothiocyanate (PEITC), which occurs as a conjugate in certain cruciferous vegetables, inhibited cell transformation corresponding with the induction of apoptosis. An elevation of p53 is required for PEITC-induced apoptosis. Our studies indicated that the chemopreventive effect of these food factors may be mediated by their effects on different signal transduction pathways; (5) retinoids (vitamin A and its metabolites) inhibited tumor promoter-induced cell transformation and tumor promotion in transgenic mice through the inhibition of AP-1 action but not through the activation of retinoic acid response element (RARE). PMID- 11216483 TI - Factors affecting flavonoids absorption. AB - In experiments on rats, some of the factors affecting flavonoids absorption (solubility, glycosylation and nutritional status: fasted and not-fasted animals) were examined. Administration of quercetin with different solubilization degree showed no direct correlation between the quercetin absorption extent and solubility, i.e. despite 3 orders of difference in solubilization degree, the extent of absorption varied only about 4-fold. Absorption comparison of genistein and its glycoside genistin showed no difference in the extent of absorption; however, aglycone, in contrast to glycoside, was absorbed already from the rat stomach. Conjugation patterns (sulfation and glucuronization) of genistein metabolites demonstrated that the plasma of animals fasted prior to isoflavone administration contained significantly more sulfates and less glucuronides and mixed sulfates/glucuronides conjugates than the plasma of non-fasted animals. PMID- 11216484 TI - Metabolic fate of luteolin and its functional activity at focal site. AB - Luteolin has been shown to possess potent antioxidant and anti-inflammatory/anti allergic activities. In order to evaluate a chemopreventive role of luteolin in inflammatory responses involved in the pathogenesis of atherosclerosis and cancer etc., the metabolic fate of luteolin in rats and humans was investigated by HPLC analysis, and its effect on cell surface expression of adhesion molecules in human umbilical vein endothelial cells(HUVECs) was examined by ELISA. Luteolin monoglucuronide, which was a main metabolite, and free luteolin were detected in rat plasma and human serum. Luteolin monoglucuronide was hydrolyzed to free luteolin by beta-glucuronidase released from neutrophils stimulated with lonomycin and Cytocharasine B. Luteolin suppressed the TNF-alpha induced ICAM-1 expression significantly. Among nine flavonoids (40 microM) examined, chrysin, apigenine, quercetin and galangin also demonstrated suppressive effct on it. These results suggest the posssibility that deconjugation of luteolin monoglucuronide occurs and that free luteolin showed functional acyivities such as suppression of TNF-alpha induced ICAM- 1 expression at inflammation site. PMID- 11216485 TI - Suppressive effects of citrus fruits on free radical generation and nobiletin, an anti-inflammatory polymethoxyflavonoid. AB - Citrus fruit intake is known to be associated with a reduction of cancer incidence. Free radicals, including superoxide (O2-) and nitric oxide (NO), are involved in some epithelial carcinogenesis processes. In the present study, we screened thirty-one citrus fruits for their suppressive activities toward three lines of free radical generating systems: 1) O2- generation by the xanthine (XA) xanthine oxidase (XOD) system; 2) O2- generation induced by 12-O tetradecanoylphorbol-13-acetate (TPA) in differentiated human promyelocytic HL-60 cells; and 3) NO generation in murine macrophage RAW264.7 cells stimulated with lipopolysaccharide (LPS) and interferon (IFN)-gamma. As a result, the inhibitory activities of peel parts were largely found to be higher than those of the corresponding juice sac parts. In particular, the peel portion of Dancy tangerine (Citrus tangerinia) showed marked anti-oxidative activities in these systems. In addition, nobiletin, a polymethoxyflavonoid isolated from C. nobilis, showed a higher anti-inflammatory activity than indomethacin in a TPA-induced edema formation test in mouse ears. These results indicate that citrus fruits could be notable sources of anti-oxidative, anti-inflammatory, and cancer preventive compounds. PMID- 11216487 TI - Suppressive effects of flavonoids on dioxin toxicity. AB - Dioxin type chemicals such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) cause a variety of toxicity. Most of the toxicity of TCDD has been attributed to a mechanism by which TCDD is bound to aryl hydrocarbon receptor (AhR) and transforms the receptor. Thus, suppression of the AhR transformation by food factors can suppress the dioxin toxicity. In this study, flavonoids at various concentrations were treated to a rat cytosolic fraction containing AhR before adding 1 nM TCDD. The transformed AhR was detected by an electrophoretic mobility shift assay with a DNA oligonucleotide consensus to dioxin response element. As the results, flavones and flavonols at dietary levels act as the antagonists for AhR and suppress the transformation. The antagonistic IC50 values were in a range between 0.14 and 10 microM, which are close to the physiological levels in human. These results suggest that a plant-based diet can prevent the dioxin toxicity. PMID- 11216486 TI - Mechanisms involved in the chemoprevention of flavonoids. AB - Flavonoids, widespread in edible plants, have been studied extensively for their anticarcinogenic properties. However, only few studies have been done with these constituents being administered by the dietary route. In our research, the effects of feeding rats with flavone, flavanone, tangeretin, and quercetin were investigated on two steps of aflatoxin B1 (AFB1)-induced hepatocarcinogenesis (initiation and promotion). Nonpolar flavonoids such as flavone, flavanone and tangeretin administered through the initiation period, decreased the number of gamma-glutamyl transpeptidase-preneoplastic foci. In the same conditions of administration, quercetin, a polyhydroxylated flavonoid, showed no protective effect. Moreover, feeding rats with flavanone during the phenobarbital-induced promotion step significantly reduced the areas of placental glutathione S transferase preneoplastic foci. Quercetin, flavone, and tangeretin, administered in the same conditions, caused no significant effect. Therefore flavanone act as an anti-initiator as well as an anti-promotor. Several mechanisms were involved in the anti-initiating effects of flavone, flavanone, and tangeretin: enhancement of enzymes involved in the detoxication of AFB1 (glutathione S-transferase, UDP glucuronyl transferase), increase of the formation of AFB1-glutathione conjugates and inhibition of the binding of AFB1 to DNA. Although the relevance of these data to the human situation remains to be demonstrated, they confirm that several flavonoids administered by the dietary route possess promising chemoprotective effects. PMID- 11216488 TI - Isoflavonoids and chronic disease: mechanisms of action. AB - Soy and its isoflavones are associated with a reduced risk of chronic disease. The mechanisms of action of isoflavones include their roles as weak estrogens, inhibitors of tyrosine kinase-dependent signal transduction processes and as cellular antioxidants. Although estrogen receptor beta binds genistein with an affinity close to that of 17beta-estradiol, it remains to be determined whether it is a mediator of genistein's activity in vivo. Genistein's inhibition of protein tyrosine kinases is not limited to direct effect on these kinases, but may result from alteration in kinase expression. Genistein is not a particularly good scavanger of cellular oxidants; however, it reacts vigorously with the prooxidant hypochlorous acid, produced by neutrophils as part of the inflammatory response. The chlorinated isoflavones may have altered biochemical and biological effects compared to their parent compounds and may provide increased protection against inflammatory disease. PMID- 11216489 TI - Comparison of plasma and urinary phytoestrogens in Japanese and Finnish women by time-resolved fluoroimmunoassay. AB - Time-resolved fluoroimmunoassays (TR-FIA), with europium labeled phytoestrogens as tracers, were developed for the quantitative measurement of genistein, daidzein and enterolactone in plasma and urine for the purpose of screening large populations and studies on possible correlation between the values in biological fluids and the risk of western diseases. The mean values of the three phytoestrogens in plasma as determined by TR-FIA were similar to those obtained by gas chromatography-mass spectrometry (GC-MS). The urinary excretion levels of total individual phytoestrogens were higher than those obtained by GC-MS, with the exception of the daidzein values. However, comparing the assay results obtained by the present method and those obtained by GC-MS, a strong correlation was evident (r = 0.87 - 0.99, p < 0.001). We measured plasma levels of genistein, daidzein and enterolactone in 111 healthy Japanese women The mean and median levels of genistein were 406.8 and 306.3 nmol/l, respectively, and those of daidzein were 118.4 and 76.8 nmol/l, respectively. These levels are higher than those reported for Americans and Western Europeans. Isoflavone intake as calculated from dietary records (genistein: mean, 86.5 mircomol/day and daidzein: mean, 57.4 micromol/day) was correlated with the plasma concentrations observed (genistein: r = 0.287, p < 0.01 and daidzein: r = 0.313, p < 0.01). Plasma enterolactone levels were low in Japanese women (mean, about 10 nmol/l). The levels of urinary excretions of genistein, daidzein were also measured and it was found that, in the majority, the levels ranged between 5-25 and 5-50 micromol/24 h, respectively. In contrast, healthy Finnish women showed very low values of isoflavones (below 10 nmol/l in plasma (n = 87) and below 0.6 micromol/24 h in urine (n = 126) for both compounds) and high levels of enterolactone in both plasma and urine (plasma: mean, 25 nmol/l and urine: majority range, 1-7 micromol/24 h). PMID- 11216490 TI - Antioxidant activity of soya hypocotyl tea in humans. AB - Antioxidative activity of isoflavones has not been shown in humans. Newly developed isoflavone-rich soya hypocotyl tea contains about 12 mg isoflavones per liter. 15 tea drinkers and 23 control young female students were randomly selected from volunteers, and underwent physical examination, blood chemistry and urinary analysis before and after one month of tea drinking. A three-day dietary record was taken before each physical examination. The tea drinkers showed a lower level of phosphatidylcholine hydroperoxide (PCOOH) and phosphatidyl ethanolamine hydroperoxide (PEOOH) in the red blood cells and a significant reduction of 8-hydroxydeoxyguanine (8ohdG) in the urine compared to the controls. PMID- 11216491 TI - Effects of isoflavone supplement on healthy women. AB - Effects of the isoflavone supplement on hormonal states in young premenopausal women were studied by cross-over study design. Administration of 20 mg or 40 mg isoflavones (IF) by tablets, of which 1 g contained 43.5 mg daidzein, 6.0 mg genistein, 24.0 mg glycitein, to 40 young female students for one month caused a prolonged menstruation in 60% of young women, shortened menstruation in 20% of young women, 17% remained unchanged and 3% became irregular. Larger dose tended to elongate more, but 17beta-estradiol levels in both follicular and luteal phages were not different between 20 mg and 40 mg isoflavone intake. Equor excreters tended to show low plasma progesteron level in the luteal phase. Detailed hormonal analysis on 3 of students by a cross over study design showed decreased level of 17beta-estradiol throughout the menstruation cycle. SHBG significantly increased about 10% in all three. DEAS, androstendione, and testosterone showed different responses according to the follicular or luteal phase. T3 and T4 increased as a result of isoflavone tablet administration in the follicular phase, but it decreased in the luteal phase. These changes suggest that isoflavones influence not only estrogen receptor-related functions but the hypothalamo-hypophysis-gonadal axis. PMID- 11216492 TI - Attenuation of neurodegeneration-relevant modifications of brain proteins by dietary soy. AB - Epidemiological studies show that postmenopausal women who undertake estrogen replacement therapy have significantly lower risk for the onset of Alzheimer's disease (AD) than women who do not. Animal behavior studies have shown that ovariectomy results in the development of cognitive dysfunction that is prevented by estrogen-replacement, suggesting that normal mammalian cognitive function is impaired by estrogen reduction. Soy isoflavones in particular genistein have been demonstrated to have weak and selective estrogenic actions in various models of human chronic diseases. A hallmark of several human dementias including AD and fronto temporal dementia with Parkinsonism on chromosome 17 (FTDP-17) is the hyperphosphorylation of the microtubule-associated protein tau. Preliminary experiments are discussed here which show that isoflavones delivered in a soy protein matrix attenuated selected AD-relevant tau phosphorylations in a primate model of menopause. The rationale is discussed for the use of soy-based foods for protection against postmenopausal neurodegeneration. PMID- 11216493 TI - The effects of soy protein in women and men with elevated plasma lipids. AB - Fifty four postmenopausal women with elevated cholesterol were recruited for a randomised, double-blind controlled trial of soy protein containing isoflavones. (ISP+) or a soy protein with a low isoflavone content (ISP-), taken daily for 12 weeks. There was an overall reduction after 12 weeks in total cholesterol (TC), LDL cholesterol (LDL-C), sex hormone binding globulin (SHBG), and luteinizing hormone (LH). There were no significant differences between treatment groups. In a separate study 27 male subjects with a TC > 5.5 mmol/l were given ISP+ for 12 weeks. In this male study there was a significant increase in HDL cholesterol (HDL-C) and SHBG. Soy protein has a cholesterol lowering effect in both women and men. These studies suggest that this effect is independent of isoflavones. Soy protein also reduces SHBG levels in both sexes. PMID- 11216494 TI - Modulation of cell-cell communication in the cause and chemoprevention/chemotherapy of cancer. AB - Chemopreventive or chemotherapeutic agents have been those that either kill cancer cells to a differential degree over the non-cancer cells or those chemicals that either block the induction of tumors in carcinogen-treated animals or retard transplanted tumors in animals. Carcinogenesis is a multi-stage, multi mechanism process, involving the irreversible alteration of a stem cell ("initiation"), followed by the clonal proliferation of the initiated cell ("promotion"). To develop a strategy for intervention with chemoprevention/chemotherapeutic chemicals, the basic mechanism(s) of carcinogenesis must be understood. Gap junction intercellular communication (GJIC) regulates cell growth, differentiation, apoptosis and adaptive functions of differentiated cells. Normal cells have functional GJIC while cancer cells do not. Tumor promoters and oncogenes inhibit GJIC, while anti-tumor promoter and anti-oncogene drugs can reverse the down-regulation of GJIC. Transfection of gap junction genes (connexins) has been shown to reverse the tumorigenic phenotype. If prevention/treatment of cancer is to occur, prevention of the chronic down regulation of GJIC by tumor promoters in non-tumorigenic but initiated cells or the up-regulation of GJIC in stably down-regulated GJIC in tumor cells must occur to prevent or to treat cancers. PMID- 11216496 TI - Anti-tumor polysaccharides from mushrooms during storage. AB - The changes in the contents of an anti-tumor polysaccharide from Lentinus edodes (lentinan) and Grifolafrondosa (GGF) during storage were investigated using by an ELISA inhibition assay. When the mushrooms were stored at low temperature, the contents of their anti-tumor polysaccharides show hardly any changes, but their contents decreased markedly at higher temperature (20 degrees C). Moreover, the effect of the extract from Lentinus edodes stored at different temperatures on tumor necrosis factor (TNF)-alpha and nitric oxide (NO) productions from macrophages was investigated to confirm the influence to the stimulation of macrophages. Because lentinan stimulates macrophages to augment their antitumor activity. Their productions showed little difference between Lentinus edodes stored at low temperature and the fresh mushroom, although the cytokine production decreased significantly in Lentinus edodes stored at 20d egrees C. These results suggest that low-temperature storage is more effective in maintaining not only the quality of the mushrooms but also the contents of anti tumor polysaccharides as health-beneficient foods. PMID- 11216495 TI - Anti-ulcer effects and biological activities of polysaccharides from marine algae. PMID- 11216497 TI - Butyrate as a model for "gene-regulating chemoprevention and chemotherapy.". AB - Recent progress in molecular genetics has facilitated understanding of the mechanisms of carcinogenesis. However, there is not yet any effective therapy or prevention for cancer based on the molecular mechanisms of carcinogenesis. So called "gene therapy" for cancer is expected to become a new method of treatment, but there are still several serious problems with gene therapy. As a matter of fact, it seems impossible to adopt gene therapy for prevention. We therefore tried to develop a different method of cancer prevention or therapy based on the molecular mechanisms of carcinogenesis. For instance, the tumor-suppressor gene p53 is mutated in about 50% of human malignancies. It is known that p53 stimulates the promoter activities of p21/WAF1, gadd45 and bax genes, resulting in cell cycle arrest, DNA repair and apoptosis, respectively. Therefore, chemical compounds that can stimulate these genes should compensate for the function of p53. As a model of this, we found that histone deacetylase inhibitors such as butyrate or trichostatin A dramatically stimulate the p21/WAF1 gene promoter through the Spl sites, resulting in cell cycle arrest. Interestingly, another group has recently reported that phenylbutyrate, which is also known as a histone deacetylase inhibitor, is very effective for leukemia patients. We therefore consider methods of up-regulating p21/WAF, gadd45 or bax genes should be useful for cancer therapy and termed this method "Gene-regulating chemotherapy". Theoretically, the chemicals up-regulating such genes should be also useful for chemoprevention, and we also termed it as "Gene-regulating chemoprevention". In conclusion, we propose that "Gene-regulating chemotherapy or chemoprevention" may be a promising new method for cancer therapy or prevention and histone deacetylase inhibitor is a good candidate for this method. PMID- 11216498 TI - When is dietary fiber considered a functional food? AB - Before answering the question of when dietary fiber can be considered a functional food we must first decide what can be called a dietary fiber. The generally accepted definition of dietary fiber is that of Trowell that dietary fiber consists of the remnants of edible plant cells polysaccharides, lignin, and associated substances resistant to (hydrolysis) digestion by the alimentary enzymes of humans. In Japan the food tables list the dietary fiber content of animal as well as plant tissues, while many countries accept saccharides of less than DP-10 as dietary fiber (inulin, oligofructose, Fibersol-2, polydextrose, fructooligosaccharides, galactooligosaccharides etc.). These shorter chain oligosaccharides do not precipitate as dietary fiber in the standard Association of Official Analytical Chemists (AOAC) method, which is accepted by the US Food & Drug Administration, the US Department of Agriculture and the Food & Agriculture Organization of the World Health Organization for nutrition labeling purposes. In the United Kingdom the term dietary fiber has been replaced in nutrition labeling by nonstarch polysaccharides. Therefore the American Association of Cereal Chemists (AACC) commissioned an ad hoc committee of scientists to evaluate continuing validity of the currently used definition, and if appropriate, to modify and update that definition. Obtaining scientific input from the community of analysts, health professionals, and dietary fiber researchers was considered a high priority. To this end three meetings were held in the space of six months to assure input from all persons knowledgeable in the field with the answer expected sometime before 2000. Dietary fiber can be considered a functional food when it imparts a special function to that food aside from the normal expected function and similarly when the dietary fiber is used as an additive to foods. For example, dietary fiber contributes to colonic health, bifidobacterial or lactobacillus stimulation in the gut, coronary artery health, cholesterol reduction, glucose metabolism, insulin response, blood lipids, cancer etc. The author discusses in detail the functional food properties of dietary fiber. PMID- 11216499 TI - Food allergens and the mucosal immune system. PMID- 11216500 TI - Effects of the administration of wheat bran biscuit: changes in the diet. AB - We developed hard biscuit containing 30% wheat bran (WB biscuit) and administered it to 12 volunteers at 7.5 g/day (7.5 g group) or 15 g/day (15 g group) as wheat bran for 12 weeks. After 12 weeks, the dietary fiber intake from foods other than wheat bran decreased slightly in the both groups, in the 15 g group was the decrease notable especially, after the beginning of WB biscuit administration. We suggest that a closest attention to changes in dietary habit associated with intervention is needed in intervention studies using patients leading a normal life. PMID- 11216501 TI - Going against the grain? Current status of the dietary fiber-colorectal cancer hypothesis. PMID- 11216502 TI - The concept of intracellular-, extracellular- and bone-minerals. AB - A new concept of grouping of minerals, which will be helpful for understanding the actual status of human health, on the basic of elementological biology. PMID- 11216503 TI - Food system-based approaches to improving micronutrient nutrition: the case for selenium. AB - Micronutrient deficiencies affect nearly half the world's population, impairing child development, reducing work productivity, and increasing mortality and morbidity rates by affecting both infectious and chronic diseases. To feed a growing world, it will be necessary to consider agriculture in the broad context of a food system as an instrument of public health and, thus, to address nutrient balance while also seeking sustainability. Such efforts would include increasing cropping system diversity, enhancing micronutrient outputs and promoting environmental sustainability. Example of this approach are presented for the essential trace element selenium (Se), which at high intakes can reduce cancer risks but is deficient in many parts of the world. Food systems-based approaches are discussed for preventing Se deficiency by enhancing intakes of any of several biologically available forms of Se, and for reducing cancer risk by enhancing intakes of forms of the element that support anti-tumorigenic Se-metabolites. PMID- 11216504 TI - Role of diet modification in cancer prevention. AB - Carcinogenesis encompasses a prolonged accumulation of injuries at several different biological levels and include both genetic and biochemical changes in the cells. At each of these levels, there are several possibilities of intervention in order to prevent, slow down or even halt the gradual march of healthy cells towards malignancy. Diet modification is one such possibility. A number of natural foodstuffs, especially fruits and vegetables contain substantial quantities of molecules that have chemopreventive potential against cancer development. Such compounds include vitamins, trace elements and a variety of other molecules with antioxidant properties. Carotenoids, flavanoid polyphenols, isoflavones, catechins, and several other components that found in cruciferous vegetables are molecules that are known to protect against the deleterious effect of reactive oxygen species. A number of epidemiological and experimental studies have shown that vitamin C and E, Beta-carotene and the essential trace element selenium can reduce the risk of cancer. Consistent observations during the last few decades that cancer risk is reduced by a diet rich in vegetables, fruits, legumes, grains and green tea have encouraged research to identify several plant components especially phytochemicals that protect against DNA damage. Many of these substances block specific carcinogen pathways. Dietary supplements are part of an overall health program, along with a high intake of fruits and vegetables that help to combat damage to cells, which in turn may initiate cancer development. This paper will review current knowledge concerning diet modification and cancer prevention with special reference to minerals and trace elements. PMID- 11216505 TI - Chemoprotection against cancer by induction of phase 2 enzymes. AB - Induction of Phase 2 enzymes is an effective and sufficient strategy for achieving protection against the toxic and neoplastic effects of many carcinogens. It is proposed that the concept of Phase 2 enzymes as being responsible only for the conjugation of functionalized xenobiotics with endogenous cellular ligands such as glutathione (glutathione S-transferases) and glucuronic acid (UDP-glucuronosyltransferases) be expanded to include proteins with the following common characteristics: (a) coordinate induction by a broad range of chemical agents that all have the capacity to react with sulfhydryl groups; (b) possible regulation by common promoter elements; and (c) catalysis of reactions that lead to comprehensive protection against electrophile and reactive oxygen toxicities, by a wide variety of mechanisms. These mechanisms include: conjugation with endogenous ligands, chemical modification of reactive features of molecules that can damage DNA and other macromolecules, and generation or augementation of cellular antioxidants. In addition to the above conjugating enzymes, a provisional and partial list of Phase 2 proteins might include: NAD(P)H:quinone reductase, epoxide hydrolase, dihydrodiol dehydrogenase, gamma glutamylcysteine synthetase, heme oxygenase-1, leukotriene B4 dehydrogenase, aflatoxin B1 dehydrogenase, and ferritin. PMID- 11216506 TI - High phosphorus feeding decreases the expression of renal PTH/PTHRP-receptor mRNA in rats. AB - Dietary intake of high phosphorus (P) is well-described to increase serum levels of PTH, however, how this increased serum PTH affects the PTH actions in major target tissues, particularly in kidney, remains uncovered. We therefore undertook to clarify this point in intact animals fed the high-P diet by examining various parameters of the PTH actions. Twelve weanling Wistar male rats were assigned randomly into the groups; a control group Ca: P = 1: 1 and a high-P group (Ca: P = 1: 3) fed the standard AIN 76 diet supplemented with P (0.5 and 1.5 g/100 g diet). After 3 week feeding, in the high-P diet group, we observed that serum Ca is lowered without difference in serum P when compared to those in the control group. Excretion of urine cAMP, an index of the renal PTH action, was also decreased with higher excretion of urine P by feeding the high P diet. In agreement with the decreased cAMP excretion, a clear reduction in the PTH/PTHrP receptor gene expression estimated by Northern blotting was observed in the kidney irrespective of increased levels of serum PTH. Thus, the present study indicated that high P dietary intake rather reduces the PTH actions in kidney though the serum PTH is increased. PMID- 11216507 TI - Influence of food ingredients on iron availability. PMID- 11216508 TI - Zinc deficiency and taste dysfunction; contribution of carbonic anhydrase, a zinc metalloenzyme, to normal taste sensation. AB - The present study was designed to clarify the effect of zinc deficiency on sodium chloride preference, the lingual trigeminal and taste nerves transduction, and carbonic anhydrase (CA) activity of the tongue surface and salivary gland. Male SD rats, 4 weeks old, were divided into four groups, and fed zinc-deficient (Zn Def), low-zinc (Low-Zn), and zinc-sufficient diets with free access (Zn-Suf) and pair-feeding (Pair-fed). After taking part in the preference tests for 42 days, the rats were provided for the chorda tympani and lingual trigeminal nerves recordings, then finally sacrificed and the tongue and submandibular gland excised to measure CA activity. Sodium chloride preference increased only after 4 days of the feeding of zinc-deficient and low-zinc diets, which means that the taste abnormality appears abruptly in zinc deficieny and even though in marginal zinc deficiency. Reduced CA activities of the taste-related tissues in zinc deficient group paralleled well with the decreased taste and lingual trigeminal nerves sensitivities. PMID- 11216509 TI - Prevention of cancer and other chronic diseases worldwide based on sound mechanisms. AB - The transformation of normal cells by DNA reactive, genotoxic carcinogens and the growth promotion and development of mutated cells by enhancing factors is involved in the overall basic mechanism of cancer induction. Thus, discrimination between genotoxic carcinogens and nongenotoxic chemicals is essential. The dose response curves, reversibility, and organ-and species specificity are distinct. Genotoxic carcinogens are mutagenic, form DNA adducts, induce DNA repair, and form hydroxy radicals and inappropriate peroxidation reactions that antioxidants such as those in vegetables, fruits, and tea can decrease. In contrast, promoters do not form DNA adducts, but raise cell duplication rates, among other attributes. In the USA, about 35% of known cancers are associated with tobacco use and about 55% with inappropriate nutritional habits. Cancer induction can be decreased by avoiding the formation of carcinogens, reducing their metabolic activation, or increasing their detoxification. Excessive dietary salt, and heterocyclic arylamines formed in cooking of meats or fish, and high intake of 40% of calories in fats are health risks, but vegetables, fruits, tea, soy products, and fibers are protective. We review nutritional factors involved in cancer and chronic disease causation and prevention. PMID- 11216510 TI - Prevention of colon carcinogenesis and carcinoma metastasis by orally administered bovine lactoferrin in animals. AB - Bovine lactoferrin (bLF), a milk protein known to have bacteriostatic properties was examined for its preventive effects on colon and other organ carcinogenesis and experimental metastasis. (Experiment 1) The influence on colon carcinogenesis was investigated in male rats treated with azoxymethane (AOM), then received 2 or 0.2% bLF for 36 weeks. Significant reduction in the incidence (27% and 46% of the control, respectively) and number of adenocarcinomas of the large intestine was observed. (Experiment 2) In BALB/c mice bearing subcutaneous (s.c.) implants of colon carcinoma 26 (Co 26Lu). bLF demonstrated significant inhibition of spontaneous lung metastasis (approximately 43% of the control). Number of cytotoxic asialoGM1+ and CD8+ cells in white blood cells increased (171% and 122% of control, respectively) after treatment. Results of those experiments indicate that bLF remarkably prevents colon carcinogenesis and lung metastasis of colon carcinoma cells, possibly due to increasing cytotoxic cells in the peripheral blood. PMID- 11216511 TI - Food containing phytoestrogens, and breast cancer. PMID- 11216512 TI - Dietary intake and cancer mortality in Japan. AB - We examined the correlation between the prefectural variation of standardized mortality ratio (SMR) for lung and colon cancer and the consumption of foods using dietary data from National Nutrition Survey in Japan from 1976 to 1995. We found partly the same results on promoting factors and preventing factors of these cancers as the previously reported large scale cohort studies. But, we also found the inconsistent results. This might be partly because of the limitation of data collection method in the National Nutrition Survey. It was thought that the method of National Nutrition Survey should be modified to monitor nutrition and health conditions to correspond the epidemiological study and to prevent chronic diseases. PMID- 11216514 TI - Diastolic dysfunction in patients with systemic sclerosis detected by gated myocardial perfusion SPECT: an early sign of cardiac involvement. AB - Diagnosis of cardiac involvement is important for the management of patients with systemic sclerosis (SSc). This study was undertaken to determine the significance of gated myocardial perfusion SPECT in patients with SSc and whether diastolic function measured by gated SPECT is an early sign of cardiac complications. METHODS: Thirty-four patients with SSc and 16 control patients were studied using exercise nongated and resting gated myocardial perfusion SPECT. The SSc was classified by the modified Rodnan total skin score (TSS) into high-TSS (score > or = 10; n = 18) and low-TSS (score < 10; n = 16) groups. Gated SPECT was performed using 99mTc-methoxyisobutylisonitrile with 16 frames per cardiac cycle and quantitatively analyzed by QGS software and Fourier filtering of the volume curve. The parameters of ejection fraction (EF), peak filling rate (PFR), one third mean filling rate, and time to PFR (TPFR) were calculated. RESULTS: A slight perfusion abnormality was observed in four and five patients in the low TSS and high-TSS groups, respectively (not statistically significant). A decreased resting EF less than 55% was found in no and two patients in the low TSS and high-TSS groups, respectively. TPFR was 166 +/- 22, 168 +/- 38, and 216 +/- 82 ms (P = 0.05, high-TSS group versus low-TSS group; P = 0.04, control group versus high-TSS group) and TPFR/R-R interval was 0.18 +/- 0.02, 0.19 +/- 0.04, and 0.26 +/- 0.09 (P = 0.01, high-TSS group versus low-TSS group; P = 0.005, control group versus high-TSS group) for the control, low-TSS, and high-TSS groups, respectively. CONCLUSION: Diastolic function can be evaluated by gated myocardial perfusion SPECT. Significant diastolic abnormalities were shown even in patients with normal perfusion and systolic function and were related to the severity of SSc. PMID- 11216516 TI - Use of wavelet transforms in analysis of time-activity data from cardiac PET. AB - Because of its intrinsic quantitative properties, PET permits measurement of myocardial perfusion and metabolism in absolute terms (i.e., mL/g/min). However, quantification has been limited by errors produced in image acquisition, selection of regions of interest, and data analysis. The goal of this study was to evaluate a newly developed, novel, wavelet-based noise-reduction approach that can objectively extract biologic signals hidden within dynamic PET data. METHODS: Quantification of myocardial perfusion using dynamic PET imaging with 82Rb, H2(15)O, and 13NH3 was selected to evaluate the effects of the wavelet-based noise-reduction protocol. Dynamic PET data were fitted to appropriate mathematic models before and after wavelet-based noise reduction to get flow estimates. Time activity curves, precision, accuracy, and differentiating capacity derived from the wavelet protocol were compared with those obtained from unmodified data processing. A total of 84 human studies was analyzed, including 43 at rest (18 82Rb scans, 18 H2(15)O scans, and 7 13NH3 scans) and 41 after coronary hyperemia with dipyridamole (17 82Rb scans, 17 H2(15)O scans, and 7 13NH3 scans). RESULTS: For every tracer tested under all conditions, the wavelet method improved the shape of blood and tissue time-activity curves, increased estimate-to-error ratios, and maintained fidelity of flow in regions as small as 0.85 cm3. It also improved the accuracy of flow estimates derived from 82Rb to the level of that achieved with H2(15)O, which was not affected markedly by the wavelet process. In studies of patients with coronary disease, regional heterogeneity of myocardial perfusion was preserved and flow estimates in infarcted regions were differentiated more easily from normal regions. CONCLUSION: The wavelet-based noise-reduction method effectively and objectively extracted tracer time-activity curves from data with low signal-to-noise ratios and improved the accuracy and precision of measurements with all tracer techniques studied. The approach should be generalizable to other image modalities such as functional MRI and CT and, therefore, improve the ability to quantify dynamic physiologic processes. PMID- 11216515 TI - Automated assessment of dipyridamole 201Tl myocardial SPECT perfusion scintigraphy by case-based reasoning. AB - This study evaluated the diagnostic accuracy of case-based reasoning (CBR) to automatically detect significant coronary artery disease from dipyridamole 201Tl myocardial SPECT perfusion scintigrams. METHODS: The study population included 240 patients (182 men, 58 women; mean age +/- SD, 61 +/- 12 y) on whom coronary angiography and perfusion scintigraphy were performed within 6 +/- 11 d of each other. The patients were divided into two groups according to the presence or absence of significant coronary disease in any major coronary vessel. Regional myocardial tracer uptake was observed in 84 segments by polar map analysis. For each scintigraphic image, a CBR algorithm based on a similarity metric was used to identify similar scintigraphic images within the case library. The angiographic results of these similar cases were used to obtain the CBR reading, which was compared with the true angiographic results. Myocardial scintigrams were also analyzed by a first-generation Cedars-Sinai (CS) method, including a comparison with a reference database, and by the visual analysis of an expert reader. RESULTS: By receiver-operating-characteristic analysis, the diagnostic accuracy of CBR was not different from the interpretation by the CS algorithm and from visual interpretation (P = not significant [NS]). For detection of significant coronary disease, the respective sensitivities at 50% and 80% specificity were 90% and 67% for CBR, 88% and 65% for CS polar map analysis, and 91% and 74% for visual interpretation. For the detection of coronary disease in the vascular territories assigned to the left anterior descending and the right coronary arteries, CBR and CS polar map analysis showed similar diagnostic accuracy (P = NS). However, for detection of disease in the circumflex artery, CS polar map analysis was slightly better than CBR (P = 0.03). CONCLUSION: Automated interpretation of dipyridamole 201Tl myocardial SPECT perfusion images by CBR has diagnostic accuracy similar to that of visual interpretation or CS analysis. Thus, use of a case library that includes a variety of normal and abnormal perfusion images does not appear to have greater diagnostic power than use of reference limits. PMID- 11216517 TI - Quantification of myocardial perfusion in human subjects using 82Rb and wavelet based noise reduction. AB - Quantification of myocardial perfusion with 82Rb has been difficult to achieve because of the low signal-to-noise ratio of the dynamic data curves. This study evaluated the accuracy of flow estimates after the application of a novel multidimensional wavelet-based noise-reduction protocol. METHODS: Myocardial perfusion was estimated using 82Rb and a two-compartment model from dynamic PET scans on 11 healthy volunteers at rest and after hyperemic stress with dipyridamole. Midventricular planes were divided into eight regions of interest, and a wavelet transform protocol was applied to images and time-activity curves. Flow estimates without and with the wavelet approach were compared with those obtained using H2(15)O. RESULTS: Over a wide flow range (0.45-2.75 mL/g/min), flow achieved with the wavelet approach correlated extremely closely with values obtained with H2(15)O (y = 1.03 x -0.12; n = 23 studies, r = 0.94, P < 0.001). If the wavelet noise-reduction technique was not used, the correlation was less strong (y = 1.11 x + 0.24; n = 23 studies, r = 0.79, P < 0.001). In addition, the wavelet approach reduced the regional variation from 75% to 12% and from 62% to 11% (P < 0.001 for each comparison) for resting and stress studies, respectively. CONCLUSION: The use of a wavelet protocol allows near-optimal noise reduction, markedly enhances the physiologic flow signal within the PET images, and enables accurate measurement of myocardial perfusion with 82Rb in human subjects over a wide range of flows. PMID- 11216518 TI - Assessment of the clinical significance of asymptomatic lower extremity uptake abnormality in young athletes. AB - This study was undertaken to evaluate our hypothesis that most asymptomatic lower extremity uptake abnormalities are of no clinical consequence and to assess whether these findings should affect patient care. METHODS: One hundred consecutive young athletes referred for bone scintigraphy by a sports medicine clinic because of low back pain were evaluated for the presence of asymptomatic bone scan abnormalities in the lower extremities. The patients were then reexamined by the referring sports medicine physician, who had full knowledge of the bone scan results. Scintigraphic findings were correlated with the clinical evaluation at the time of scintigraphy and on follow-up evaluations ranging from 8 to 14 mo later. RESULTS: Asymptomatic lower extremity abnormalities were present in 34% of patients. There were abnormalities of the feet in 30 patients (focal uptake in 26 patients, diffuse uptake in 10 patients), the tibia in 13 patients (2 focal uptake, 11 diffuse uptake), and the femur in 2 patients (both with diffuse uptake). None of the regions of abnormal lower extremity uptake was symptomatic at the time of initial evaluation. There was no change in the clinical management of any patient because of the scan findings. None of the patients was advised to restrict the activity level because of the asymptomatic scan findings. None of the regions of scan abnormality became symptomatic on follow-up evaluation. CONCLUSION: This study shows that asymptomatic bone scintigraphic abnormalities of the feet, as well as diffuse abnormalities of the tibia, are common in young athletes. These findings are most likely of no clinical consequence and do not require a change in the activity level. Focal abnormalities of the femur or tibia are not commonly seen in asymptomatic young athletes. PMID- 11216519 TI - 64Cu-TETA-octreotide as a PET imaging agent for patients with neuroendocrine tumors. AB - 64Cu (half-life, 12.7 h; beta+, 0.653 MeV [17.4%]; beta-, 0.579 MeV [39%]) has shown potential as a radioisotope for PET imaging and radiotherapy. (111)In diethylenetriaminepentaacetic acid (DTPA)-D-Phe1-octreotide (OC) was developed for imaging somatostatin-receptor-positive tumors using conventional scintigraphy. With the advantages of PET over conventional scintigraphy, an agent for PET imaging of these tumors is desirable. Here, we show that 64Cu-TETA-OC (where TETA is 1,4,8,11-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid) and PET can be used to detect somatostatin-receptor-positive tumors in humans. METHODS: Eight patients with a history of neuroendocrine tumors (five patients with carcinoid tumors and three patients with islet cell tumors) were imaged by conventional scintigraphy with (111)In-DTPA-OC (204-233 MBq [5.5-6.3 mCi]) and by PET imaging with 64Cu-TETA-OC (111 MBq [3 mCi]). Blood and urine samples were collected for pharmacokinetic analysis. PET images were collected at times ranging from 0 to 36 h after injection, and the absorbed doses to normal organs were determined. RESULTS: In six of the eight patients, cancerous lesions were visible by both (111)In-DTPA-OC SPECT and 64Cu-TETA-OC PET. In one patient, (111)In-DTPA-OC showed mild uptake in a lung lesion that was not detected by 64Cu TETA-OC PET. In one patient, no tumors were detected by either agent; however, pathologic follow-up indicated that the patient had no tumors. In two patients whose tumors were visualized with (111)In-DTPA-OC and 64Cu-TETA-OC, 64Cu-TETA-OC and PET showed more lesions than (111)In-DTPA-OC. Pharmacokinetic studies showed that 64Cu-TETA-OC was rapidly cleared from the blood and that 59.2% +/- 17.6% of the injected dose was excreted in the urine. Absorbed dose measurements indicated that the bladder wall was the dose-limiting organ. CONCLUSION: The high rate of lesion detection, sensitivity, and favorable dosimetry and pharmacokinetics of 64Cu-TETA-OC indicate that it is a promising radiopharmaceutical for PET imaging of patients with neuroendocrine tumors. PMID- 11216520 TI - Somatostatin receptor scintigraphy in the initial staging of low-grade non Hodgkin's lymphomas. AB - In this prospective study, somatostatin receptor (SS-R) scintigraphy was compared with conventional staging procedures for the initial staging of patients with low grade non-Hodgkin's lymphoma (NHL). METHODS: Fifty consecutive untreated patients with low-grade NHL underwent SS-R scintigraphy as part of their initial staging. Planar images were obtained 24 and 48 h after intravenous injection of 220 MBq (111)In-pentetreotide. SPECT images of the upper abdomen were obtained from all patients. SS-R scans were evaluated blindly without knowledge of the results of the conventional staging methods. SS-R scintigraphy findings were compared with the results of physical and radiologic examinations. RESULTS: SS-R scintigraphy findings were positive in 42 of 50 patients (84%). In 10 patients (20%), the SS-R scan revealed new lesions that had not been revealed by conventional staging procedures. These 10 patients were all upgraded to a higher stage. Consequently, the treatment plan would have been altered in 5 patients (10%). However, in 19 patients (38%), lesions apparent after conventional staging methods were missed by SS-R scintigraphy. The sensitivity of SS-R scintigraphy varied from 62% for supradiaphragmatic lesions to 44% for infradiaphragmatic lesions. The specificity of SS-R scintigraphy was high (98%-100%). In comparison with CT scanning and sonography, SS-R scintigraphy is inferior for the visualization of NHL lesions in the thorax and abdomen. CONCLUSION: Although SS-R scintigraphy findings are positive in a large proportion of patients with low-grade NHL, in most patients only part of the lesions can be visualized. Because of the limited sensitivity, we recommend SS-R scintigraphy for initial staging of patients with low-grade NHL only in selected conditions and not for the general work-up. PMID- 11216521 TI - Skeletal uptake and soft-tissue retention of 186Re-HEDP and 153Sm-EDTMP in patients with metastatic bone disease. AB - The aim of this study was to introduce a new quantification method for 153Sm ethylenediaminetetramethylenephosphonate (EDTMP) and 186Re-(tin)1,1 hydroxyethylidene diphosphonate (HEDP) to separately measure bone uptake and soft tissue retention of these radiopharmaceuticals. METHODS: Studies were performed on 23 men and 6 women undergoing radionuclide therapy for palliation of bone pain. Whole-body images were acquired at 3 min, 3-4 h, and 24-72 h after injection of 1,295 MBq 186Re-HEDP and 37 MBq 153Sm-EDTMP per kilogram of body weight. The activities for whole body, urinary bladder, and both thighs, as representative of soft tissue, were measured by region-of-interest technique. A background region of interest adjacent to the head was used to correct for bremsstrahlung. Bone uptake was calculated as initial whole-body activity minus urinary excretion and remaining soft-tissue activity. RESULTS: For 186Re-HEDP (n = 11) the mean bone uptake at 3 h after injection was 13.7% +/- 8.6% of initial whole-body activity. The remaining soft-tissue activity was 49.4% +/- 16.9%, and urinary excretion was 36.9% +/- 14.4%. At 24 h after injection, bone uptake reached a value of 21.8% +/- 9.0%. Urinary excretion increased to 65.3% +/- 12.8% according to a decreasing soft-tissue remainder activity of 12.8% +/- 5.4%. The corresponding results for 153Sm-EDTMP (n = 18) at 3 h after injection were 29.2% +/- 15.5% for bone uptake, 32.3% +/- 12.9% for urinary excretion, and 38.4% +/- 14.5% for soft tissue. At 24 h after injection, we calculated values of 47.7% +/- 11.2% for bone uptake, 39.5% +/- 13.8% for urinary excretion, and 12.7% +/- 4.7% for soft tissue. CONCLUSION: Bone uptake and soft-tissue retention for both 186Re HEDP and 153Sm-EDTMP as obtained in this study agree well with the conventional 24-h whole-body retention measurements for these tracers. However, by this new scintigraphic quantification method, bone uptake and soft-tissue retention can be calculated separately, thus providing more detailed kinetic data and potentially improving the dosimetry of these radiopharmaceuticals in, for example, assessment of radiation dosage to bone and bone marrow. PMID- 11216522 TI - Neuroblastoma imaging using a combined CT scanner-scintillation camera and 131I MIBG. AB - High-dose administration of 131I-metaiodobenzylguanidine (131I-MIBG) continues to be a promising treatment for neuroblastoma. However, currently used methods of estimating 131I-MIBG uptake in vivo may be too inaccurate to properly monitor patient radiation exposure doses. To improve localization and uptake measurements over currently practiced techniques, we evaluated different methodologies that take advantage of the correlated patient data available from a combined CT scintillation camera imaging system. METHODS: Serial CT and radionuclide scans of three patients were obtained on a combined imaging system. SPECT images were reconstructed using both filtered backprojection and maximum-likelihood expectation maximization (MLEM). Volumes of interest (VOIs) were defined on anatomic images and automatically correlated to spatial volumes in reconstructed SPECT images. Several radionuclide quantification methods were then compared. First, the mean reconstructed values within coregistered SPECT VOIs were estimated from MLEM reconstructed images. Next, we assumed that reconstructed activity in SPECT voxels were linear combinations of activities present in individual objects, weighted by geometric factors derived from CT images. After calculating the weight factors by modeling the SPECT imaging process with anatomically defined VOIs, least-squares fitting was used to estimate the activities within lesion volumes. We also estimated the lesion activities directly from planar radionuclide images of the patients using similar linearity assumptions. Finally, for comparison, lesion activities were estimated using a standard conjugate view method. RESULTS: Activities were quantified from three patients having a total of six lesions with volumes ranging from 0.67 to 117 mL. Methods that used CT data to quantify lesion activities gave similar results for planar and tomographic radionuclide data. Estimating activity directly from mean VOI values in MLEM-reconstructed images alone consistently provided estimates lower than CT-aided methods because of the limited spatial resolution of SPECT. Values obtained with conjugate views produced differences up to fivefold in comparison with CT-aided methods. CONCLUSION: These results show that anatomic information available from coregistered CT images may improve in vivo localization and measurement of 131I-MIBG uptake in tumors. PMID- 11216523 TI - Quantitative PET studies in pretreated melanoma patients: a comparison of 6 [18F]fluoro-L-dopa with 18F-FDG and (15)O-water using compartment and noncompartment analysis. AB - The purpose of the study was to evaluate the 6-[18F]fluoro-L-dopa (FDOPA) kinetics with PET in patients with treated melanoma metastases and to compare it with the standard tracer 18F-FDG as well as with the perfusion tracer (15)O-water in selected cases. METHODS: The study included 11 patients (22 lesions) with pretreated metastatic melanomas. Dynamic studies with FDG and in selected cases with (15)O-water (eight patients) preceded the FDOPA study. A one-tissue compartment model was used for the evaluation of the FDOPA and (15)O-water studies, and a two-tissue-compartment model and Patlak analysis were used for the FDG data. A noncompartment model based on chaos theory was used for calculating fractal dimension, which is a parameter for heterogeneity. RESULTS: The FDG studies showed a 1.5-fold increased uptake in comparison with surrounding tissue in 19 of 22 metastatic lesions (sensitivity of 86.4%). False-negative FDG results were obtained in 2 patients (three lesions). FDOPA uptake was enhanced in 14 of 22 metastatic lesions (sensitivity of 64%). FDG uptake was 1.5-fold higher than FDOPA uptake in 18 of 22 metastases from melanoma, whereas FDOPA uptake was 1.5 fold higher than FDG uptake in 2 patients with liver metastases. The data did not show a statistically significant correlation between the transport constant (K1) for FDOPA and that for FDG or between the standardized uptake value for FDOPA and FDG in metastases. No statistically significant correlation was found between K1 for FDOPA and that for (15)O-water. The data show that FDOPA uptake is not perfusion dependent and provides different information from FDG. The fractal dimension was similar for all tracers within the tumor region. Detectability of metastases was enhanced when both tracers were used (sensitivity of 95%). CONCLUSION: In patients with negative FDG findings, FDOPA can help to identify viable melanoma metastases and thus may help to select patients who would benefit from further treatment. PMID- 11216524 TI - Combined 18F-FDG-FDOPA tumor imaging for assessing response to therapy. PMID- 11216525 TI - Brain SPECT in clinical practice. Part I: perfusion. AB - Brain perfusion SPECT is a functional neuroimaging technique that allows noninvasive study of physiologic and physiopathologic events in the human brain. With the appropriate technique and careful interpretation of the information provided, brain perfusion SPECT has proven potential for patient management. SPECT has clinical value in the diagnosis, therapeutic management, and follow-up of patients. The diversity of central nervous system diseases and the still incomplete knowledge of the mechanisms that underlie them have contributed to the success of brain perfusion SPECT as a research tool in neurosciences. This article provides fundamental knowledge on how and when to perform brain perfusion SPECT in clinical practice. A general overview of the clinical value of this technique is followed by relevant information on cerebral physiology for proper understanding of brain SPECT images. Practical considerations on quantification and interventional studies are also offered. Finally, step-by-step recommendations for interpreting and reporting brain perfusion SPECT images are provided to obtain the maximum clinical benefit from this technique. PMID- 11216526 TI - Kinetic analysis of 125I-iodorotenone as a deposited myocardial flow tracer: comparison with 99mTc-sestamibi. AB - The goal of this investigation was to assess the accuracy of 7'-Z [125I]iodorotenone (125I-iodorotenone) as a new deposited myocardial flow tracer and compare the results with those for 99mTc-sestamibi. METHODS: The kinetics of these two flow tracers were evaluated in 25 isolated, erythrocyte- and albumin perfused rabbit hearts over a flow range relevant to patients. The two flow tracers and a vascular reference tracer (131I-albumin) were introduced simultaneously as a compact bolus through a port just above the aortic cannula in the absence of tracer recirculation. Myocardial extraction, retention, washout, and uptake parameters were computed from the venous outflow curves using the multiple-indicator dilution technique and spectral analysis. RESULTS: The extraction of 125I-iodorotenone was much higher than the extraction of 99mTc sestamibi (0.84 +/- 0.05 vs. 0.48 +/- 0.10, respectively, P < 0.001). 125I iodorotenone extraction was also less affected by flow than was 99mTc-sestamibi (P < 0.001). Net retention of 125I-iodorotenone was significantly greater than 99mTc-sestamibi net retention at 1 min (0.77 +/- 0.08 vs. 0.41 +/- 0.11, respectively, P < 0.001) and 26 min (0.46 +/- 0.13 vs. 0.27 +/- 0.11, respectively, P < 0.001) after tracer injection. Flow had less effect on 125I iodorotenone net retention than on 99mTc-sestamibi net retention 1 min after tracer injection (P < 0.04). However, at 26 min, flow had an equivalent effect on the retention of both flow tracers (P < 0.4). The relationship between 125I iodorotenone and 99mTc-sestamibi washout was complex and depended on elapsed time after isotope introduction and perfusion rate. Reflecting the favorable extraction and retention characteristics of 125I-iodorotenone, both its maximum myocardial uptake and its 26-min uptake were more closely related to flow than were those of 99mTc-sestamibi (P < 0.001 for both comparisons). CONCLUSION: The extraction and retention of 125I-iodorotenone were greater than those of 99mTc sestamibi, making 125I-iodorotenone the superior flow tracer in the isolated rabbit heart. PMID- 11216527 TI - The quest for the perfect myocardial perfusion indicator...still a long way to go. PMID- 11216528 TI - Serial changes in 14C-deoxyglucose and 201Tl uptake in autoimmune myocarditis in rats. AB - This study was designed to examine the relationships between the uptake of 14C deoxyglucose (DG) and the uptake of 201Tl in a rat model of autoimmune myocarditis. METHODS: Autoimmune myocarditis was induced in normal rats by immunization with pig cardiac myosin. Dual-tracer autoradiography with DG and 201Tl was performed on frozen slices of the animals' hearts 3 wk (acute phase), 8 wk (subacute phase), and 14 wk (chronic phase) (each n = 5) after immunization. The extent of inflammatory damage was classified histologically into three categories on the basis of cell infiltration: mild (Mi), moderate (Mo), and severe (Sv). The regional count in the region of interest set on the autoradiogram was normalized on the basis of that of control rats. The ratio of total cardiac uptake to the injected dose (%ID/g x BW, where ID is injected dose and BW is body weight) was calculated by tissue counting. Expressions of glucose transporters GLUT1 and 4 were evaluated by the enzyme-labeled antibody method. RESULTS: The total cardiac uptake of DG in the acute phase of myocarditis was significantly higher than in normal control rats (3.43% +/- 0.92% vs. 0.97% +/- 0.38%; P < 0.0001); it then decreased in the chronic phase but was still higher than in the controls (1.85% +/- 0.37% vs. 0.97% +/- 0.38%; P < 0.01). The total cardiac uptake of 201Tl in the acute phase of myocarditis was significantly lower than in the controls (7.4% +/- 0.7% vs. 12.0% +/- 3.3%; P < 0.005); it then increased in the chronic phase and reached normal levels (13.0% +/- 3.3% vs. 12.0% +/- 3.3%; not significant [NS]). In the acute phase, the regional uptakes of DG in the Mi, Mo, and Sv regions were 143.1% +/- 107.9%, 169.6% +/- 59.9%, and 317.5% +/- 103.3%, respectively, whereas those of 201Tl were 88.4% +/- 31.9%, 72.1% +/- 34.6%, and 48.4% +/- 21.5%, respectively. GLUT expression was evaluated visually and classified into four grades (0, 1, 2, and 3). In the acute phase, GLUT1 expression was higher in rats in the Sv group than in the controls (2.87 vs. 0.87). GLUT4 was not expressed in the Sv areas but was found in the Mi areas. CONCLUSION: In the acute phase of autoimmune myocarditis in rats, cardiac uptake of DG was accelerated by severe inflammation. Cardiac uptake of 201Tl, on the other hand, was suppressed. Our results suggest that GLUT1 expression accelerates DG uptake by cells in areas of severe inflammation. PMID- 11216529 TI - Early retardation of 99mTc-DTPA radioaerosol transalveolar clearance in irradiated canine lung. AB - The alteration of 99mTc-labeled diethylenetriaminepentaacetic acid (DTPA) transalveolar clearance in an initial phase of radiation lung injury was experimentally investigated. METHODS: Fourteen dogs were irradiated to the hemithorax with a single dose of 20 Gy. A DTPA radioaerosol study was performed before irradiation and on day 12 after irradiation. On day 14, the DTPA study was repeated again, with seven animals undergoing the study after inhalation of an aerosolized synthetic surfactant. The penetration index (P.I.) and clearance half time (T(1/2)) of DTPA were measured in each lung. To evaluate the changes in lung surfactant after irradiation, alveolar lipids were stained in the resected lungs (n = 14), and the amounts of alveolar surfactant phospholipid and protein were measured by a bronchoalveolar lavage study in another six irradiated dogs. RESULTS: In all of the 14 irradiated animals, DTPA radioaerosol distributed uniformly throughout the lungs without significant changes in P.I. The T(1/2) values in irradiated lungs were significantly prolonged compared with the matched baseline values and those in nonirradiated lungs (P < 0.05 and 0.001, respectively). The aerosolized synthetic surfactant retarded the DTPA clearance both in the irradiated and in the nonirradiated lungs (P < 0.001) without significant changes in P.I. The histologic and bronchoalveolar lavage studies revealed an increase of alveolar surfactant materials in the irradiated lungs without substantial histologic changes in the alveolar structures. CONCLUSION: DTPA transalveolar clearance was retarded soon after irradiation. Increased alveolar surfactant may be partly responsible for this retarded DTPA clearance because the aerosolized synthetic surfactant also prolonged the clearance in nonirradiated lungs. A DTPA clearance test is sensitive for the early detection of radiation lung injury and seems helpful for clarifying the association of epithelial integrity changes and lung surfactant in radiation lung injury. PMID- 11216530 TI - Absolute activity quantitation in simultaneous 123I/99mTc brain SPECT. AB - Dual-isotope imaging can allow simultaneous assessment of brain perfusion using a 99mTc-labeled tracer and neurotransmission using an 123I-labeled tracer. However, the images are affected by scatter, cross talk, attenuation, distance-dependent collimator response (DCR), and partial-volume effect. We determined the accuracy and precision of activity quantitation in simulated normal and pathologic studies of simultaneous 123I/99mTc brain SPECT when compensating for all degrading phenomena. METHODS: Monte Carlo simulations were performed using the Zubal brain phantom. Contamination caused by high-energy 123I decay photons was incorporated. Twenty-four 99mTc and 123I activity distributions were simulated on the basis of normal and pathologic patient activity distributions. Cross talk and scatter were corrected using a new method based on a multilayer perceptron artificial neural network (ANN), as well as by the asymmetric window (AW) approach; for comparison, unscattered (U) photons of 99mTc and 123I were recorded. Nonuniform attenuation and DCR were modeled in an iterative ordered-subset expectation maximization (OSEM) algorithm. Mean percentage biases and SDs over the 12 normal and 12 pathologic simulated studies were computed for each structure with respect to the known activity distributions. RESULTS: For 123I, AW + OSEM yielded a bias of 7% in the cerebellum, 21% in the frontal cortex, and 36% in the corpus callosum in the simulated normal population. The bias was increased significantly in the striata of simulated pathologic studies (P < 0.05). The bias associated with ANN was significantly lower (<9% in these brain structures, P < 0.05). For 99mTc with AW + OSEM, the bias was 60% in the corpus callosum, 36% in the striata, and 18% 22% in the cortical lobes in the simulated normal population. This bias was <11% in all brain structures with ANN. In the simulated pathologic population, the bias associated with AW increased significantly in the cortical lobes to 55% (P < 0.05), although it did not change significantly with ANN. CONCLUSION: The accuracy and variability over simulated normal and pathologic studies of both 99mTc and 123I activity estimates were very close with ANN to those obtained with U + OSEM. ANN + OSEM is a promising approach for absolute activity quantitation in simultaneous 99mTc/123I SPECT. PMID- 11216531 TI - Imaging cyclophosphamide-induced intramedullary apoptosis in rats using 99mTc radiolabeled annexin V. AB - Intramedullary apoptosis of hematopoietic tissue is believed to play a major role in the pathophysiology of myelodysplastic syndrome. Annexin V, a specific marker of the early to intermediate phases of apoptosis, has been applied to the in vitro study of bone marrow aspirates. A noninvasive measure of intramedullary apoptosis in vivo that could serially monitor the clinical progression of myelodysplastic syndrome may be helpful. METHODS: We used 99mTc-radiolabeled annexin V and radionuclide gamma camera imaging to serially study the sites, extent, and severity of intramedullary apoptosis induced by cyclophosphamide treatment. RESULTS: Intravenously administered radiolabeled annexin V localized preferentially in the femur, pelvis, vertebrae, and spleen; increased uptake in these organs was easily visualized as early as 8 h after injection of 100 mg/kg cyclophosphamide in 8- to 10-wk-old animals. Higher doses of cyclophosphamide (150 mg/kg) in animals of the same age increased annexin V uptake in the bone marrow and splenic tissue and delayed recovery of these organs as seen histologically compared with lower doses. Older animals, 5-6 mo old, showed a slower response to cyclophosphamide treatment and delayed recovery of bone marrow and splenic tissues. CONCLUSION: Radiolabeled annexin V can be used to detect and directly quantify the degree of intramedullary and splenic apoptosis in a noninvasive fashion using current clinical radionuclide imaging equipment. Annexin V imaging may be useful clinically in the diagnosis and management of myelodysplastic syndrome. PMID- 11216532 TI - Transfer of the human NaI symporter gene enhances iodide uptake in hepatoma cells. AB - The characteristic feature of thyroid cells of taking up iodide enables benign thyroid diseases and differentiated thyroid carcinoma to be successfully treated with radioiodide therapy. The transport of iodide across the cell membrane is mediated by the human NaI symporter (hNIS). We therefore investigated whether the accumulation of iodide may be induced by the retroviral transfer of the hNIS gene in nonthyroid tumor cells. METHODS: With use of a bicistronic retroviral vector for the transfer of the hNIS coding sequence and the hygromycin resistance gene, rat Morris hepatoma (MH3924A) cells were infected with retroviral particles and 32 hNIS-expressing cell lines were generated by hygromycin selection. After incubation of the genetically modified and wild-type hepatoma cells and the rat thyroid cell line FRTL5 with Na125I, the uptake and efflux of iodide were determined. In addition, the iodide distribution in rats bearing wild-type and genetically modified hepatomas was monitored. RESULTS: Genetically modified MH3924A cell lines accumulated up to 235 times more iodide than did noninfected hepatoma cells. The maximal iodide uptake in the cells was observed after 60 min incubation time. Competition experiments in the presence of sodium perchlorate revealed a dose-dependent decrease of iodide uptake (87%-92%). Moreover, carbonyl cyanide p-trifluoromethoxyphenylhydrazone led to a loss of accumulated I- (32%), whereas 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene increased the I- uptake into the cells (22%). However, a rapid efflux of the radioactivity (80%) was observed during the first 10 min after 125I(-)-containing medium had been replaced by nonradioactive medium. In rats, the hNIS-expressing tumors accumulated six times more iodide than did the contralateral wild-type tumor as monitored by scintigraphy. The ex vivo quantitation of the iodide content performed 1 h after tracer administration in 1 g of tumor tissue revealed a 17 fold higher iodide accumulation in the genetically modified tumors. In accordance with the in vitro data, we also observed a rapid efflux of radioactivity from the tumor in vivo. CONCLUSION: The transduction of the hNIS gene per se is sufficient to induce 125I transport in Morris hepatoma cells in vitro and in vivo. With regard to a therapeutic application, however, additional conditions need to be defined that inhibit the iodide efflux from the tumor cells. PMID- 11216533 TI - Glycosylated RGD-containing peptides: tracer for tumor targeting and angiogenesis imaging with improved biokinetics. AB - The alpha(v)beta3 integrin plays an important role in metastasis and tumor induced angiogenesis. Targeting with radiolabeled ligands of the alpha(v)beta3 integrin may provide information about the receptor status and enable specific therapeutic planning. Previous studies from our group resulted in tracers that showed alpha(v)beta3-selective tumor uptake. However, these first-generation compounds predominantly revealed hepatobiliary excretion with high radioactivity found in the liver. In this report, the synthesis and biological evaluation of the first glycosylated RGD-containing peptide (RGD-peptide) for the noninvasive imaging of alpha(v)beta3 expression are described. METHODS: Peptides were assembled on a solid support using fluorenylmethoxycarbonyl-coupling protocols. The precursor cyclo(-Arg-Gly-Asp-D-Tyr-Lys(SAA)-) GP1 was synthesized by coupling 3-acetamido-2,6-anhydro-4,5,7-tri-O-benzyl-3-deoxy-beta-D-glycero-D-gulo-heptonic acid (SAA(Bn3)) with cyclo(-Arg(Mtr)-Gly-Asp(OtBu)-D-Tyr(tBu)-Lys-) and subsequent removal of the protection groups. Iodine labeling was performed by the Iodo-Gen method (radiochemical yield > 50%). The in vitro binding assays were performed using purified immobilized alpha(IIb)beta3, alpha(v)beta5, and alpha(v)beta3 integrins. For in vivo experiments, nude mice bearing xenotransplanted melanomas and mice with osteosarcomas were used. RESULTS: The glycosylated peptide 3-iodo-Tyr4-cyclo(-Arg-Gly-Asp-D-Tyr-Lys(SAA)-) GP2 showed high affinity and selectivity for alpha(v)beta3 in vitro (50% inhibitory concentration = 40 nmol/L). Pretreatment studies indicate specific binding of [125I]GP2 on alpha(v)beta3-expressing tumors in vivo. Comparison of the pharmacokinetics of [125I]GP2 and [125I]-3-iodo-Tyr4-cyclo(-Arg-Gly-Asp-D-Tyr-Val ) [125I]P2 revealed for [125I]GP2 an increased activity concentration in the blood (e.g., 3.59 +/- 0.35 percentage injected dose [%ID]/g vs. 1.72 +/- 0.44 %ID/g at 10 min postinjection) and a significantly reduced uptake in the liver (e.g., 2.59 +/- 0.24 %ID/g vs. 21.96 +/- 2.78 %ID/g at 10 min postinjection). Furthermore, a clearly increased activity accumulation in the tumor was found (e.g., 3.05 +/- 0.31 %ID/g vs. 0.92 +/- 0.16 %ID/g at 240 min postinjection), which remained almost constant between 60 and 240 min postinjection. This resulted in good tumor-to-organ ratios for the glycosylated tracer (e.g., 240-min postinjection osteosarcoma model: tumor-to-blood = 16; tumor-to-muscle = 7; tumor to-liver = 2.5), which were confirmed by the first gamma-camera images of osteosarcoma-bearing mice at 240 min postinjection. CONCLUSION: This study demonstrates that the introduction of a sugar moiety improves the pharmakokinetic behavior of a hydrophobic peptide-based tracer. Additionally, this alpha(v)beta3 selective glycosylated radioiodinated second-generation tracer GP2 shows high tumor uptake and good tumor-to-organ ratios that allow noninvasive visualization of alpha(v)beta3-expressing tumors and monitoring therapy with alpha(v)beta3 antagonists. Finally, the favorable biokinetics make the glycosylated RGD-peptide a promising lead structure for tracers to quantify the alpha(v)beta3 expression using PET. PMID- 11216534 TI - Marking hypoxia in rat prostate carcinomas with beta-D-[125I]azomycin galactopyranoside and. AB - The purpose of this study was to determine, with a rodent tumor model, if microelectrode measurements of unmodulated tumor oxygenation predict for the avidity of hypoxic markers to tumor tissue. METHODS: The rapidly growing, anaplastic variant of the Dunning rat prostate carcinoma cell line (R3327-AT) was implanted subcutaneously on the upper backs of Fischer X Copenhagen rats. Approximately 100 measurements of PO2 were obtained from tumors of 5-10 g in animals that were restrained and then subjected to different anesthetic procedures. Values of median PO2 (in mm Hg) and percentage of measurements <5 mm Hg obtained from individual tumors were used to define tumor oxygenation status. The radiodiagnostic hypoxic markers beta-D-iodinated azomycin galactopyranoside (IAZGP) and [99mTc]HL-91 were simultaneously administered to 26 animals whose tumor oxygen levels had been measured. Six hours after marker administration, the animals were killed; tumor, blood, and muscle tissues were sampled; and percentage injected dose per gram (%ID/g*), tumor/blood ratio (T/B), and tumor/muscle ratio (T/M) parameters were determined. Parameters of marker avidity to individual tumors were linearly correlated with microelectrode measurements of tumor oxygenation to determine the significance of inverse associations. RESULTS: The median PO2 of 41 tumors varied from 2.0 to 20.9 mm Hg, with an average value of 7.5 +/- 1.4 mm Hg. Six tumors had unusually high values; that is, >10 mm Hg, and when these were excluded from the analysis, the average median PO2 of the remaining 35 was 4.3 +/- 0.7 mm Hg. When electrode measurements of tumor oxygenation were obtained under conditions of halothane anesthesia with the animals breathing O2, carbogen, or air, median PO2 values increased significantly (P = 0.001). When animals were deeply anesthetized by intraperitoneal injection of ketamine-xylazine, median PO2 values were not significantly different (P = 0.13) from those obtained while the animals were restrained and breathing air. There was no inverse correlation of significance between the electrode measurements of median PO2 and the avidity of beta-D-IAZGP nor [99mTc]HL-91 in this tumor model. The range of median PO2 values in these tumors was at least 3 mm Hg, and the range of hypoxic marker avidity was less than twofold. CONCLUSION: These data demonstrate that microelectrode measurements of rat tumor oxygenation did not correlate with the avidity of the two hypoxic markers, at least in this tumor model. The larger dynamic range of tumor oxygen measurements obtained with microelectrodes might be biased to low values by their necrotic fractions, the zones within solid tumors that contain dead cells and debris that will not be labeled by bioreducible hypoxic markers. Hypoxic marker avidity to individual tumors will have to be validated by other assays that can predict for their radiosensitivity. PMID- 11216535 TI - Preclinical evaluation of locoregional delivery of radiolabeled iododeoxyuridine and thymidylate synthase inhibitor in a hepatoma model. AB - We report improved incorporation of the radiolabeled-thymidine analog [125I/131I]5-iodo-2'-deoxyuridine ([125I/131I]IdUrd) into DNA by the addition of Thymitaq, a thymidylate synthase inhibitor, as a strategy of molecular radiotherapy for hepatoma treatment. METHODS: The synergistic effect of combination [125I]IdUrd and Thymitaq in clonogenic survival and DNA incorporation was shown on the human hepatoma cell line Hep3B. Radiobiodistribution of intrahepatic arterially injected [125I]IdUrd and Thymitaq was studied in a rat N1S1 hepatoma model. In vivo therapeutic effects of locoregional delivery of both drugs were evaluated in mouse subcutaneous hepatoma and ascitic hepatoma models. RESULTS: In a clonogenic assay, Thymitaq showed a synergistic effect with [125I]IdUrd but not cold IdUrd. Thymitaq had a dose-dependent modulation effect on DNA-[125I]IdUrd incorporation. The biodistribution study indicated a slower clearance rate of [125I]IdUdR in the hepatoma as well as an initially higher uptake of [125I]IdUrd into DNA when the [125I]IdUrd was combined with Thymitaq. In vivo studies showed a superior therapeutic effect of combination Thymitaq and [125I]IdUrd in both subcutaneous and ascites tumor models, but the combination of [131I]IdUrd and [125I]IdUrd may be more effective than Auger electron emitters alone for the treatment of subcutaneous tumor. CONCLUSION: The strategy of locoregional delivery of [125I/131I]IdUrd to a tumor site through an intrahepatic arterial, intratumoral, or intraperitoneal route in combination with Thymitaq is promising and may also have a favorable therapeutic index in vivo. PMID- 11216536 TI - Performance of a dual, solid-state intraoperative probe system with 18F, 99mTc, and (111)In. AB - The use of tracer-avid radiopharmaceuticals and handheld, intraoperative, radiation-sensitive probes to localize areas of tumors promises to improve surgical treatments of cancer. Currently several beta- and gamma-ray-emitting radiopharmaceuticals are proposed for use in these procedures. Therefore, intraoperative-probe systems should be capable of optimum performance with several different radionuclides. The goal of this study was to evaluate the performance of a dual, solid-state probe with three of these radionuclides (18F, 99mTc, and (111)In). METHODS: The detector unit of the intraoperative-probe system used in this investigation consisted of a stack of two ion-implanted silicon detectors separated by 0.5 mm. The system could be operated in two modes: beta optimized, in which the difference between the signals from the two detectors was calculated to correct the beta signal for photon contamination, and photon-optimized mode, in which the signals were summed. Detection sensitivity and an index measuring beta detection selectivity were measured in both acquisition modes with the three different radionuclides. The gamma-ray detection sensitivity of a commercially available probe was measured with 99mTc and compared with the results with a solid-state probe. RESULTS: Beta and photon emissions (gamma-rays and annihilation photons) produced by all three radionuclides were detected by the probe. In beta-optimized acquisition mode, the greatest beta-detection sensitivity was achieved with 18F; photon sensitivity was greatest for measurements with (111)In. The lowest detection sensitivities (beta and photon) were obtained with 99mTc. With the probe system in gamma-optimized mode, the greatest beta and photon sensitivities were achieved with 18F; the lowest were obtained with 99mTc. The gamma-detection sensitivity measured with 99mTc in gamma mode (5.59 +/- 0.41 counts per second [cps]/kBq) compared surprisingly well with the results from the commercial probe (8.75 +/- 0.47 cps/kBq). CONCLUSION: The results from this investigation demonstrate the flexibility and versatility of the dual, solid-state probe system used in this study. These capabilities may be used to improve existing techniques or lead to new methods for performing radionuclide-guided surgeries. PMID- 11216537 TI - Automated stereotactic standardization of brain SPECT receptor data using single photon transmission images. AB - Intra- or intersubject registration of anatomically poorly defined SPECT data, such as in neuroreceptor imaging, is important for longitudinal or group analysis. However, accurate registration is difficult with only emission CT (ECT) data. We investigated fully automated registration using transmission CT (TCT) data as an intermediary image set. METHODS: The accuracy of TCT registration was compared to that of ECT registration for four types of data: gray-matter distribution (with [99mTc]ethylcysteinate dimer (ECD)), neocortical distribution (with [123I]R91150, a highly specific 5-HT2a receptor ligand), and striatal distribution of the D2-receptor ligand (with [123I]iodobenzamide (IBZM)) and the dopamine transporter ligand (with [123I]2beta-carbomethoxy-3beta-(4 fluorophenyl)tropane (CIT)). In total, 10 datasets of the various study types were used, all collected on a Toshiba GCA9300 gamma camera with super-high resolution fanbeam collimators and 3 x 370 MBq of 153Gd transmission sources (4 min sequential TCT scanning for receptor studies and 20-min simultaneous scanning for [99mTc]ECD studies). Per dataset, 15 random misalignments of 9 rigid-body parameters (translation, rotation, and anisotropic scaling) were conducted. All coregistrations were done twice, both to the subject's original scan and to a study-specific template. This was done manually by two independent experienced observers and with three automated voxel similarity algorithms: mutual information (M.I.), count difference (C.D.), and uniformity index (U.I.). As an outcome measure, the impact of misregistration on semiquantification for the various study types was established. RESULTS: TCT matching allowed registration within 3.3 mm, 2.4 degrees, and 1.2% scaling (mean squared values for all directions) with an overall accuracy decrease in the following order: C.D. > M.I. > manual > U.I. For [99mTc]ECD and [123I]IBZM, TCT registration was as accurate as ECT registration, while it was far superior for the other receptor data types, especially for abnormal studies. The automated TCT registration accuracy corresponded to average quantification errors of 2.9% ([99mTc]ECD), 4.2% ([123I]BZM), 5.7% ([123I]R91150), and 6.1% ([123I]beta-CIT). CONCLUSION: Fully automated registration through intermediary TCT images is clinically feasible, fast, and accurate. In addition to nonuniform attenuation correction, TCT scanning therefore allows coregistration for group comparisons of SPECT receptor data on a standardized or pixel-by-pixel basis. PMID- 11216538 TI - Biodistribution and radiation dosimetry of the dopamine transporter ligand. AB - 18F-labeled 2 beta-carbomethoxy-3beta-(4-chlorophenyl)-8-(-2 fluoroethyl)nortropane ([18F]FECNT) is a recently developed dopamine transporter ligand with potential applications in patients with Parkinson's disease and cocaine addiction. METHODS: Estimates of the effective dose equivalent and doses for specific organs were made using biodistribution data from 16 Sprague-Dawley rats and nine rhesus monkeys. PET images from two rhesus monkeys were used to calculate the residence time for the basal ganglia. The computer program MIRDOSE3 was used to calculate the dosimetry according to the methodology recommended by MIRD. RESULTS: The basal ganglia were the targeted tissues receiving the highest dose, 0.11 mGy/MBq (0.39 rad/mCi). The effective dose equivalent was 0.018 mSv/MBq (0.065 rem/mCi), and the effective dose was 0.016 mSv/MBq (0.058 rem/mCi). CONCLUSION: Our data show that a 185-MBq (5-mCi) injection of [18F]FECNT leads to an estimated effective dose of 3 mSv (0.3 rem) and an estimated dose to the target organ or tissue of 19.4 mGy (1.93 rad). PMID- 11216539 TI - Patient dosimetry of intravenously administered 99mTc-annexin V. AB - Annexin V labeled with 99mTc is evaluated as a potential in vivo marker for tissue with increased apoptosis. Promising results in patients have been obtained with 99mTc-(n-1-imino-4-mercaptobutyl)-annexin V (99mTc-i-AnxV). Because information on biodistribution and radiation burden is desired for the application of any radiopharmaceutical, a dosimetric study of 99mTc-i-AnxV was undertaken. METHODS: Eight persons with normal kidney and liver functions were included in this study: six patients with myocardial infarction, one with Crohn's disease, and one healthy volunteer. Approximately 600 MBq 99mTc-i-AnxV were injected intravenously immediately before a dynamic study with a dual-head gamma camera in conjugate view mode. In the next 24 h, two to four whole-body scans were acquired. Patient thickness was determined from a transmission scan with a 57Co flood source. Organ uptake was estimated after correction for background, attenuation, and scatter, using a depth-independent buildup factor and an organ size-dependent attenuation correction. Residence times were calculated from the dynamic and whole-body studies and used as input for the MIRDOSE 3.1 program to obtain organ-absorbed doses and effective dose. RESULTS: Activity strongly accumulated in the kidneys (21% +/- 6% of the injected dose at 4 h postinjection) and the liver (12.8% +/- 2.2%). Uptake in the target tissues (myocardium or colon) was limited and negligible from a dosimetric point of view. The biologic half-life of activity registered over the total body was 62 +/- 13 h. Of the excreted activity, approximately 75% went to the urine and 25% to the feces. The absorbed dose for the more strongly exposed organs was (in microGy/MBq): kidneys, 93 +/- 24; spleen, 22 +/- 6; liver, 17 +/- 2; testes, 15 +/- 3; thyroid, 10 +/- 6; urinary bladder wall, 7.5 +/- 2.6; and red bone marrow, 5.5 +/- 0.8. The effective dose was 9.7 +/- 1.0 microSv/MBq, corresponding to a total effective dose of 5.8 +/- 0.6 mSv for a nominally injected activity of 600 MBq. CONCLUSION: 99mTc-i-AnxV strongly accumulates in the kidneys and to a lesser degree in the liver. The associated effective dose per MBq is in the midrange of values found for routine 99mTc-labeled compounds. From a dosimetric point of view 99mTc-i-AnxV is therefore well suited for the study of apoptosis in patients. PMID- 11216540 TI - Advanced medical imaging project. PMID- 11216541 TI - Hemodialysis in a patient being treated with 153Sm. PMID- 11216542 TI - New algorithm for quantification of myocardial perfusion SPECT. PMID- 11216543 TI - HIPAA: the promise of privacy--at what cost? PMID- 11216544 TI - Managing ultrafiltration failure by peritoneal resting. PMID- 11216545 TI - How should iron be given to peritoneal dialysis patients? PMID- 11216546 TI - Optimization of fill volumes in automated peritoneal dialysis. PMID- 11216547 TI - Optimal volume prescription for children on peritoneal dialysis. PMID- 11216548 TI - Guidelines for the treatment of peritonitis in children. PMID- 11216549 TI - Consensus guidelines for the treatment of peritonitis in pediatric patients receiving peritoneal dialysis. PMID- 11216550 TI - Prevention of peritonitis in children on peritoneal dialysis. AB - We reviewed methods of preventing peritonitis in children. A considerable body of evidence indicates that peritonitis rates are lowest with the use of a double cuffed catheter, with a downward directed tunnel, placed by an experienced surgeon. Evidence in adults, but lacking in children, suggests that exit-site mupirocin will lower Staphylococcus aureus exit-site infections and thus peritonitis rates. The risk of peritonitis due to contamination can be diminished by the avoidance of spiking and by the provision of a long training period. Catheter removal and replacement for catheter-related peritonitis may be done simultaneously in certain circumstances and is useful in decreasing the risk of recurrent peritonitis. Antibiotic prophylaxis at the time of catheter insertion, for contamination, during dialysate leaks, and for invasive procedures appears to be useful in diminishing peritonitis risk. PMID- 11216551 TI - Risk factors responsible for ultrafiltration failure in early stages of peritoneal dialysis. AB - OBJECTIVE: To define risk factors for ultrafiltration failure (UFF) during early stages of peritoneal dialysis (PD). DESIGN: Retrospective analysis of a group of patients whose peritoneal function was prospectively followed. SETTING: A tertiary-care public university hospital. PATIENTS: Nineteen of 90 long-term PD patients required a peritoneal resting period to recover UF capacity: 8 had this requirement before the third year on PD (early, EUFF group) and 11 had a late requirement (LUFF group). The remaining 71 patients, those with stable peritoneal function over time, constituted the control group. MAIN OUTCOME MEASURES: Peritoneal UF capacity under standard conditions (monthly) and small solute peritoneal transport (yearly). RESULTS: None of the conditions appearing at the start of PD or during the observation period could be definitely identified as the cause of UFF. There were no differences in characteristics between the EUFF group and the other two groups, except for the higher prevalence of diabetes in the EUFF group. Residual renal function (RRF) declined in all three groups during the first 2 years, with rapid loss during the third year in the EUFF group. This rapid loss in RRF was coincident with UFF. Peritoneal solute and water transport at baseline was similar in the three groups. After 2 years on PD, individuals in the EUFF group showed a significantly lower UF and higher creatinine mass transfer coefficient values than those in the LUFF group. Diabetic patients in the control group showed remarkable stability in UF capacity over time. During the second year on PD, requirement for increases in dialysate glucose concentration was 3.4 +/- 0.5% in the LUFF group, but as high as 25.5 +/- 24.2% in the EUFF group. The accumulated days of active peritonitis (APID, days with cloudy effluent) were similar for the three groups after 1, 2, and 3 years on PD. Interestingly, diabetic patients in the control group showed an APID index significantly lower than the overall EUFF group. Diabetics in the control group also had significantly lower APID versus nondiabetics in the control group (p = 0.016). CONCLUSIONS: Our findings suggest that certain patients develop early UFF type I. Diabetic state and a higher glucose requirement to obtain adequate UF suggest that glucose on both sides of the peritoneal membrane could be responsible. The mechanisms for this higher requirement remain to be elucidated. The identification of a larger cohort of these early UFF patients should lead to a better exploration of the primary pathogenic mechanisms. PMID- 11216552 TI - High peritoneal permeability predisposes to hepatic steatosis in diabetic continuous ambulatory peritoneal dialysis patients receiving intraperitoneal insulin. AB - OBJECTIVE: To evaluate hepatic fat accumulation in diabetic patients taking intraperitoneal or subcutaneous insulin treatment during continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Cross-sectional study. SETTING: Tertiary-care university hospital. PATIENTS: We studied 16 patients with diabetic end-stage renal disease currently treated with CAPD. Median age was 42 years (range: 34-70 years), duration of diabetes was 27.5 years (range: 17-39 years), and duration of CAPD was 16.5 months (range: 2-59 months). OUTCOME MEASURES: Ultrasound measures of liver steatotic area and thickness, peritoneal equilibration test (PET), weekly Kt/V urea, protein catabolic rate (PCR), hemoglobin A1c (HbA1c), lipoproteins, alanine aminotransferase, alkaline phosphatase, insulin dose, and dialysate glucose load. RESULTS: Focal hepatic fat accumulation was found. The location of steatosis was subcapsular; a negligible amount was periportal. Hepatic subcapsular steatosis was present in 7 of 8 patients taking insulin intraperitoneally and in 0 of 8 patients taking insulin subcutaneously. The maximal thickness of subcapsular steatosis correlated directly with peritoneal transport rate (2-hour dialysate-to-plasma creatinine ratio in PET, r = 0.80, p < 0.05) and inversely with PCR (r = -0.82, p < 0.05). The area of the lesions correlated directly with body weight (r = 0.80, p < 0.05) and inversely with weekly Kt/V urea (r = -0.90, p < 0.01). CONCLUSIONS: Intraperitoneal insulin, together with glucose-based peritoneal dialysate, induces hepatic subcapsular steatosis. The amount of hepatic subcapsular steatosis increases when peritoneal transfer rate and body weight are high. PMID- 11216553 TI - Advanced glycosylation end-products in diabetic rats on peritoneal dialysis using various solutions. AB - OBJECTIVE: To evaluate and compare the effects of glucose-based solutions to those of icodextrin with respect to peritoneal transport characteristics and advanced glycosylation end-product (AGE) formation in the peritoneal membrane in a diabetic rat model of peritoneal dialysis (PD). DESIGN: Thirty-three male Sprague-Dawley rats weighing between 275-300 g were divided into five groups: group C (n = 6), control rats implanted with a catheter but not dialyzed; group D (n = 5), diabetic rats implanted with a catheter but not dialyzed; group G (n = 7), diabetic rats implanted with a catheter and dialyzed with standard 2.5% glucose solution for daytime exchanges and 4.25% glucose solution for overnight exchanges; group H (n = 8), diabetic rats implanted with a catheter and dialyzed with standard 2.5% glucose solution for daytime exchanges and 7.5% icodextrin solution for overnight exchanges; group I (n = 7), diabetic rats implanted with a catheter and dialyzed with 7.5% icodextrin solution for all exchanges. Dialysis exchanges (25 mL per exchange) were performed three times daily for a period of 12 weeks. Tissue sections were stained using a monoclonal anti-AGE antibody. One hour peritoneal equilibration tests (PET) were performed every 4 weeks for comparison of transport characteristics. RESULTS: The level of immunostaining was lowest in group C and highest in group G. Significant differences in immunostaining were seen between group C and group G (p < 0.001), group C and group H (p = 0.001), and group C and group I (p < 0.05). Significant differences were also found between group G and group D (p < 0.05), and between group G and group I (p < 0.05). Over time, the ratio of glucose concentration after 1 hour to glucose concentration at instillation (D/D0) decreased and the dialysate-to plasma ratio (D/P) of urea increased. Significant differences in D/D0 glucose and D/P urea were found between group C and group H (D/D0: 0.40 +/- 0.01 vs 0.35 +/- 0.01, p < 0.05; D/P urea: 0.87 +/- 0.03 vs 0.97 +/- 0.02, p < 0.05). CONCLUSIONS: These results suggest that AGE formation is lower with the use of peritoneal dialysis solution containing icodextrin than with glucose-based solution. We conclude that use of icodextrin may help to slow the deterioration of the peritoneal membrane, prolonging its use for dialysis. PMID- 11216554 TI - Marked variation in peritoneal insulin absorption in peritoneal dialysis. AB - OBJECTIVE: To assess both peritoneal insulin absorption and adsorption of insulin to the plastic delivery system, and to assess whether variation in peritoneal absorption is related to transport status. DESIGN: Eight insulin-dependent diabetic patients on continuous ambulatory peritoneal dialysis were studied. Insulin was added to the dialysate. The amount adsorbed by the bag tubing was determined; peritoneal absorption was measured by complete spent dialysate collection. RESULTS: Only 14% +/- 5% of added insulin was adsorbed onto the dialysate delivery system. Marked variation in peritoneal absorption occurred (38% +/- 14%, range 17%-66%). Variations in membrane transport status did not account for variation in absorption. CONCLUSION: Marked variation in peritoneal absorption of insulin occurs, accounting for some of the variation in intraperitoneal insulin requirements. This is not related to membrane transport status. PMID- 11216555 TI - Intraperitoneal infusion of glucose-based dialysate in the rat--an animal model for the study of peritoneal advanced glycation end-products formation and effect on peritoneal transport. AB - OBJECTIVE: Glucose-based dialysate induces non enzymatic glycation within the peritoneal cavity. To evaluate the relationship between the formation of advanced glycation end-products (AGEs) and peritoneal transfer for small solutes and macromolecules, we developed a model of simulated peritoneal dialysis (PD) in normal rats. METHODS: Male albino rats of the Charles River strain were divided into two sets of 3 groups (15-25 rats in each group). In the experimental (E) group, the rats were intraperitoneally (i.p.) injected daily with a commercially available 4.25% dextrose solution. In the control puncture (CP) group, the peritoneum was punctured daily, but no PD solution infused. In an age-matched control (CC) group, no intervention was given. Two study protocols were used. Protocol A (duration 20 weeks) consisted of a daily i.p. injection of 10 mL PD solution per 100 g body weight. In protocol B, a double volume of PD solution was introduced (20 mL per 100 g body weight). At 9, 16, and 20 weeks in protocol A, and at 9 weeks in protocol B, urea, creatinine, microalbumin [(MAL) measured using specific anti-rat albumin monoclonal antibody], and AGEs (measured by fluorescent assay with excitation at 370 nm and emission at 440 nm) were measured in peritoneal effluent and serum. RESULTS: At no time during the study were AGEs detected in serum from any group in either protocol. In both protocols, no differences were found between the control groups (CP, CC) with respect to all parameters. In protocol A, the dialysate-to-plasma ratio (D/P) of urea was significantly higher in the experimental group as compared with the control groups at 9, 16, and 20 weeks [9 weeks: 0.59 +/- 0.03 (E) vs 0.39 +/- 0.02 (CP) vs 0.46 +/- 0.02 (CC), p < 0.0004 and p < 0.002, respectively; 16 weeks: 0.71 +/- 0.08 (E) vs 0.42 +/- 0.01 (CP) vs 0.46 +/- 0.01 (CC), p < 0.0001 and p < 0.02, respectively; 20 weeks: 0.57 +/- 0.03 (E) vs 0.39 +/- 0.01 (CP) vs 0.41 +/- 0.02 (CC), p < 0.002 and p < 0.004, respectively]. At 16 and 20 weeks, dialysate MAL levels were significantly increased in group E [16 weeks: 354.00 +/- 80.35 microg/mL (E) vs 134.75 +/- 14.36 microg/mL (CP) vs 110.69 +/- 7.83 microg/mL (CC), p < 0.04 and p < 0.03, respectively; 20 weeks: 283.17 +/- 14.71 microg/mL (E) vs 105.14 +/- 12.11 microg/mL (CP) vs 135.50 +/- 19.03 microg/mL (CC), p < 0.00001 and p < 0.0001, respectively]. In protocol B, at completion of the study (week 9), D/P urea, effluent MAL, and AGEs were significantly higher in the experimental group as compared with the control groups [D/P: 0.67 +/- 0.04 (E) vs 0.46 +/- 0.07 (CP) vs 0.41 +/- 0.02 (CC), p < 0.0002 and p < 00001, respectively; MAL: 336.8 +/- 63.30 microg/mL (E) vs 125.71 +/- 16.77 microg/mL (CP) vs 119.00 +/- 39.75 microg/mL (CC), p < 0.008 and p < 0.007, respectively; AGEs: 265.77 +/- 33.49 U/mg creatinine (E) vs 163.10 +/- 21.99 U/mg creatinine (CP) vs 83.17 +/- 22.66 U/mg creatinine (CC), p < 0.02 and p < 0.001, respectively]. Peritoneal effluent AGEs were found to be significantly correlated with D/P urea and dialysate MAL (r = 0.42, p < 0.04, and r = 0.7, p = 0.00001, respectively). CONCLUSIONS: In situ generation of AGEs constitutes the chief origin of peritoneal AGEs. Advanced glycation end-products affect peritoneal permselectivity for both small and large solutes. The rat model of simulated peritoneal dialysis developed in this experiment provides a reliable method for studying peritoneal AGE formation and effect on peritoneal transfer of small solutes and macromolecules. PMID- 11216556 TI - Iron absorption after single pharmacological oral iron loading test in patients on chronic peritoneal dialysis and in healthy volunteers. AB - OBJECTIVE: Oral iron is poorly absorbed in chronic dialysis patients. We tested the hypothesis that a superpharmacologic dose of iron sulfate (260 mg elemental iron) administered on an empty stomach results in significant iron absorption in these patients. DESIGN: A prospective open controlled trial. SETTING: Outpatient department of a university hospital. PATIENTS: Nine stable chronic peritoneal dialysis (PD) patients and seven normal control subjects. METHOD: All subjects ingested a single dose of 4 tablets of iron sulfate (260 mg elemental iron total) in the morning while fasting. OUTCOME MEASURES: Serum iron concentrations at baseline, and at 2 and 4 hours after the oral dose were compared between the two groups. RESULTS: The control group showed a significant rise in mean [standard error (SE)] serum iron concentration, from a baseline value of 76.5 +/- 7 microg/dL to 191 +/- 10.5 microg/dL at 2 hours and to 190 +/- 24 microg/dL at 4 hours. This result represents a percentage rise of 164% +/- 32% at 2 hours and 152% +/- 28.5% at 4 hours. In the PD patients, a significant rise in serum iron concentration was also seen, from a baseline value of 64 +/- 8 microg/dL to 130 +/- 3 microg/dL at 2 hours and 111 +/- 18 microg/dL at 4 hours. This result represents a percentage rise of 105% = 29% at 2 hours and 77% +/- 23.5% at 4 hours. However, the absolute change in serum iron concentration in PD patients at 2 and 4 hours was approximately equal to 50% of the change in control subjects at those time points. None of the PD patients experienced gastrointestinal side effects; 4 control subjects experienced mild side effects. CONCLUSION: Despite impaired oral iron absorption in chronic dialysis patients, a large pharmacologic dose given orally can result in significant iron absorption and may prove to be a more efficient means of oral iron supplementation therapy in these patients. PMID- 11216557 TI - Is absorption of high-dose oral iron sufficient in peritoneal dialysis patients? AB - OBJECTIVE: Iron supplementation plays a major role in erythropoietin-treated end stage renal disease patients. For peritoneal dialysis (PD) patients, oral iron substitution is more convenient than intravenous therapy. However, disturbed iron absorption and adverse effects may be limiting factors for oral treatment. Nevertheless, we compared the response to a high-dose and low-dose oral iron absorption test between PD patients and healthy control subjects. PATIENTS AND INTERVENTIONS: In 34 PD patients and 15 healthy control subjects, blood samples were taken at baseline as well as 2, 4, and 8 hours after oral intake of 4 tablets iron sulfate (105 mg elemental iron per tablet). In a subgroup of 6 PD patients and 6 control subjects, the oral iron absorption test was repeated using 1 tablet iron sulfate. RESULTS: There was no significant difference in the increase in serum iron during the test between the two groups. As known for healthy subjects, iron absorption was significantly better in PD patients with absolute iron deficiency compared to those with functional iron deficiency. Iron repleted PD patients showed the lowest iron absorption, indicating that a high dose of oral iron did not overwhelm the ability of the bowel tract to reject unneeded iron. Increasing the oral iron dose from 1 to 4 tablets was followed by a better response in a small subgroup of PD patients compared to control subjects. Side effects such as nausea and vomiting occurred more frequently during high-dose oral iron in control subjects than in PD patients (20% vs 8.8%). CONCLUSION: High-dose oral iron is well absorbed in iron-depleted PD patients. This kind of oral iron therapy should be considered in some subgroups of PD patients with iron deficiency, particularly in those patients with poor vascularization of arm veins or intolerance to intravenous iron preparations. PMID- 11216558 TI - Incidence of peritonitis in chronic peritoneal dialysis patients infused with intravenous iron dextran. AB - BACKGROUND: The Dialysis Outcomes Quality Initiative (DOQI) guidelines, published in 1997, emphasize the need for careful monitoring of iron stores and for provision of adequate iron replacement therapy to achieve target goals of hemoglobin concentration in end-stage renal disease (ESRD) patients, especially those treated with recombinant erythropoietin (rHuEPO). Intravenous iron dextran (IVID) therapy, which has long been used in hemodialysis patients, is increasingly being used in chronic peritoneal dialysis (CPD) patients. In 1997, we began using this form of iron therapy for our CPD patients. However, because considerable data exists to show a relationship between iron metabolism and acute infections, we questioned whether IVID infusion placed our patients at greater risk for peritonitis, the leading cause of death and patient drop-out from CPD therapy. OBJECTIVE: To evaluate the relationship between iron and infection, we studied episodes of peritonitis in CPD patients who were infused with IVID. DESIGN: In a retrospective study of adult CPD patients who received IVID during 1998, we investigated the occurrence of peritonitis episodes and the spectrum of causative organisms. Patients with a hemoglobin level of < 12.5 g/dL who also had a ferritin level < 100 ng/mL or a transferrin saturation level < 20% (or both) and who did not respond to oral iron therapy, were administered between 0.5 g and 1.0 g of IVID in an outpatient hospital setting. We calculated the expected and observed number of peritonitis episodes in these patients within 30, 60, and 90 days after infusion of IVID. RESULTS: During the study period, 56 patients received 77 doses of IVID, with 14 patients requiring 2 or more infusions. Of the 77 doses, 71 were given as a 1-g bolus. The IVID was well tolerated by all patients. Within 90 days of IVID administration, 14 patients developed peritonitis: 6 episodes occurred within 30 days, 7 episodes occurred between 31 and 60 days, and 1 episode occurred between 61 and 90 days after the IVID dosing. The peritonitis rate for patients not receiving IVID was 1 episode per 13.7 patient-months. Taking this rate as the "expected" rate, the expected number of episodes of peritonitis for the study population was 5.6 episodes within 30 days, 11.2 episodes within 60 days, and 16.8 episodes within 90 days following IVID administration. The difference between the expected and observed rates of peritonitis in patients who were dosed with IVID was not statistically different. The spectrum of organisms seen in the peritonitis episodes in the study population was not significantly different from that seen in the peritonitis episodes in our CPD unit population. CONCLUSIONS: There is evidence that IVID infusion therapy can improve anemia and reduce rHuEPO requirements in CPD patients, usually without adverse reaction and without exposing patients to an increased risk of peritonitis. More research is needed in the area of potential increased risk of infection in ESRD patients who are (1) infused with large doses of IVID, and (2) iron-overloaded. PMID- 11216559 TI - Longitudinal study of peritoneal membrane function in continuous ambulatory peritoneal dialysis: relationship with peritonitis and fibrosing factors. AB - BACKGROUND: The peritoneal equilibration test (PET) is a useful assessment of peritoneal function in continuous ambulatory peritoneal dialysis (CAPD) patients. However, the natural course of longitudinal change in peritoneal transport is not well defined. PATIENTS: We studied 105 unselected CAPD patients. Average age at enrollment was 50.7 +/- 11.3 years. METHODS: A PET was performed at enrollment. Peritoneal transport was expressed as dialysate-to-plasma creatinine ratio at 4 hours (DIP). Fibrosing factors and mesothelial cell markers, including TGFbeta, epidermal growth factor (EGF), platelet-derived growth factor (PDGF), hyaluronan, and cancer antigen 125 (CA125), were measured in overnight peritoneal dialysate effluent (PDE). Patients were followed for two years. Peritonitis episodes were recorded. Severe peritonitis was defined as an episode that required catheter removal or antibiotic therapy for more than 3 weeks. After two years, 75 patients were still alive and on CAPD. RESULTS: The PET was repeated in 64 patients, of whom 35 were male and 9 had diabetes. The change in D/P over two years was represented as AD/P. No significant change in peritoneal transport was seen after two years (D/P: 0.56 +/- 0.12 vs 0.55 +/- 0.13). A centripetal pattern of change in D/P was observed. The deltaD/P had normal distribution and was inversely correlated with D/P at baseline (r = -0.427, p < 0.005). Both results suggest a regression-to-mean phenomenon. The deltaD/P had no significant correlation with the total number of peritonitis episodes (Spearman r = 0.052, p = 0.74), but after severe peritonitis, affected patients had higher deltaD/P than patients who experienced no severe infection (0.040 +/- 0.136 vs -0.032 +/- 0.120, p < 0.05). For patients with no episodes of severe peritonitis (n = 47), deltaD/P was weakly correlated with baseline TGFbeta level (r = -0.506, p < 0.01). No correlation was seen between the levels of other fibrosing factors and change in peritoneal transport. CONCLUSIONS: Our findings suggest that the centripetal change of peritoneal transport probably reflects a regression-to-mean phenomenon. Peritoneal transport increases after severe peritonitis. The role of TGFbeta levels in PDE with regard to longitudinal change in peritoneal transport requires further study. PMID- 11216560 TI - Intermittent intravenous piperacillin pharmacokinetics in automated peritoneal dialysis patients. AB - BACKGROUND: Use of intermittent antibiotic dosing is increasing in the treatment of peritoneal dialysis (PD)-related peritonitis. We studied the pharmacokinetics of intravenous (i.v.) piperacillin in automated PD patients. PATIENTS AND METHODS: Eight patients (3 males, 5 females) were recruited and received a single i.v. dose of piperacillin (35 mg/kg actual body weight). Blood and dialysate samples were collected at the beginning, middle, and end of dwells 1-3 (on cycler), and end of dwells 4-5 (off cycler) for a 24-hour period. Baseline and 24 hour urine samples (nonanuric patients, n = 7) were collected. Pharmacokinetic parameters were calculated assuming a one-compartment model. Glomerular filtration rate (GFR) and piperacillin clearance (CL) values were normalized to 1.73 m2. RESULTS: The patients were 49.5 +/- 10.1 years of age (mean +/- SD) and had been receiving PD for a median of 3 months (range 2-66 months). Dwell times were 2.25 +/- 0.06 hours on cycler and 7.26 +/- 0.14 hours off cycler. Piperacillin half-life was not statistically different on or off the cycler (on cycler 1.99 +/- 0.39 hr, off cycler 4.39 +/- 5.4 hr; p = 0.12) and remained insignificant, even accounting for an outlier (on cycler 2.01 +/- 0.41 hr, off cycler 2.54 +/- 1.48 hr; p = 0.19). Piperacillin total CL (CL(T)) was 31.29 +/- 6.02 mL/minute. Renal CL (CL(R)) and PD CL (CL(PD)) accounted for 8.8% and 16.8% of CL(T); CL(R) correlated well with GFR (CL(R) = 0.86 GFR + 0.1; p < 0.00003). Mean piperacillin serum and dialysate end-of-dwell concentrations were above minimum inhibitory concentration of susceptible organisms (8 microg/mL) for the three cycler exchanges only. Serum and dialysate concentrations predicted using a one-compartment model suggest that i.v. piperacillin 4000 mg would provide adequate concentrations for susceptible organisms over a 12-hour period. CONCLUSION: The current i.v. piperacillin dosing recommendations of 4000 mg every 12 hours for PD-related peritonitis are appropriate for patients on automated PD. Intermittent intraperitoneal piperacillin is not recommended. PMID- 11216561 TI - Correlation of intraperitoneal antibiotic pharmacokinetics and peritoneal membrane transport characteristics. AB - OBJECTIVE: To identify correlations between the pharmacokinetic variables that describe drug disposition in peritoneal dialysis (PD) patients and the measures used to assess dialysis adequacy. DESIGN AND METHODS: This retrospective study re evaluated data collected during previous pharmacokinetic studies for intraperitoneally administered cefazolin, ceftazidime, and gentamicin in continuous ambulatory peritoneal dialysis (CAPD) patients, and intravenous cefazolin and tobramycin in automated PD patients. Pharmacokinetic variables were compared to creatinine clearance (CCr), Kt/V, and peritoneal equilibration test data using the Pearson product correlation coefficient (r). RESULTS: Prominent correlations were found between renal CCr and renal Kt/V, with renal clearances of CAPD cefazolin and ceftazidime, and automated PD tobramycin and cefazolin (r values ranged from 0.698 to 0.986; p < 0.05). CONCLUSION: These findings support current peritonitis treatment recommendations that patients with residual renal function may require higher doses or more frequent drug administration. PMID- 11216562 TI - Chronic peritoneal inflammation by cyanate in rats. AB - OBJECTIVE: During peritoneal dialysis, the peritoneum is exposed to waste products, including urea. Urea forms cyanate spontaneously at body temperature and pH, and cyanate carbamylates amino acids, peptides, and proteins. Cyanate may contribute to peritoneal injury with morphological changes in the peritoneum. To test this hypothesis, we injected cyanate into rats. METHODS: Experiments were performed in two groups of 7 rats each. In the cyanate group, each rat received 1 mL of 1.5 micromol/L potassium cyanate dissolved in 40 mmol/L sodium bicarbonate solution intraperitoneally each experiment day. In the control group, each rat received 1 mL of 1.5 micromol/L potassium bicarbonate instead of potassium cyanate. The rats in both groups were anesthetized and killed at the 85th day after the first injection. After formalin fixation, tissue samples from abdominal walls and livers were sliced, embedded in a standard manner, and stained with hematoxylin and eosin. RESULTS: Parietal peritoneum from rats in the cyanate group showed a mild increase in the number of fibroblasts, with collagen deposits, infiltration by mononuclear cells, vascular congestion, round-shaped transformation of mesothelial cells, widening of submesothelial spaces, and abundant denudation of mesothelial cells. The visceral peritoneum from rats in the cyanate group showed collagen deposits with fibroblastic proliferation. CONCLUSIONS: Cyanate can induce chronic inflammation in the peritoneum, and exposure of the peritoneum to cyanate may contribute to peritoneal injury in patients being treated with peritoneal dialysis. PMID- 11216563 TI - Serum albumin and other serum protein fractions in stable patients on peritoneal dialysis. AB - BACKGROUND: Hypoalbuminemia is common in peritoneal dialysis (PD) patients; but the reduction in serum albumin levels (SAlb) that should be expected in stable PD patients is less clear. OBJECTIVES: To determine prospectively, in a group of stable PD patients without comorbid conditions, the changes in SAlb concentration and in the concentrations of the other serum protein fractions. To investigate the best determinants of a significant decrease in SAlb levels. DESIGN: Prospective observational study. METHODS: Seventeen PD patients in stable clinical condition, with no signs of systemic inflammatory response, were included in the study. SAlb and the electrophoretic pattern of serum proteins were determined immediately before PD start, and after 6, 9, 12, 15, 18, 21, and 24 months on PD. In each study period, clinical characteristics, adequacy parameters, protein catabolic rate (PNPNA: protein equivalent of non protein nitrogen appearance), and protein losses were determined. Patients were divided into two subgroups according to whether SAlb decreased less than 10%, or 10% or more, from baseline values after 24 months on PD. The main differences between the subgroups were investigated. RESULTS: Mean SAlb did not decrease significantly after 24 months on PD (from baseline 3.99 +/- 0.46 g/dL to 3.80 +/- 0.54 g/dL), though percentage SAlb values did (58.36% +/- 5.58% vs 55.15% +/- 5.42%, p < 0.01). A weak increase in alpha2-globulin was observed after 18 months on PD (from 10.62% +/- 2.53% to 12.96% +/- 2.51%, p = 0.001). Alpha-globulin showed a sustained increase from a mean baseline value of 3.51% +/- 1.09% to 6.83% +/- 2.13% after 24 months (p < 0.0001). Seven patients had a reduction in SAlb greater than 10% after 24 months on PD. Kt/V urea and residual renal function tended to be lower in patients whose SAlb decreased. Mean PNPNA was significantly lower in patients who had a reduction in SAlb (0.76 +/- 0.12 g/kg/day vs 0.96 +/- 0.12 g/kg/day, p < 0.0001). However, total protein loss was even greater in patients who had no SAlb reduction. CONCLUSIONS: After 24 months on PD, a mean reduction in SAlb of 10%-15% from baseline values should be expected only in those stable patients whose PNPNA is low. PMID- 11216564 TI - The role of lean body mass as a nutritional index in Chinese peritoneal dialysis patients--comparison of creatinine kinetics method and anthropometric method. AB - OBJECTIVE: To compare, in Chinese continuous ambulatory peritoneal dialysis (CAPD) patients, the creatinine kinetics method (LBM-CK) and the anthropometric method (LBM-AM) for determining lean body mass (LBM). DESIGN: Single-center cross sectional study. PATIENTS AND METHODS: We studied 151 unselected CAPD patients (78 males, 73 females). We calculated LBM-CK and LBM-AM using standard formulas. The results of the two methods were then compared by the Bland and Altman method. Dialysis adequacy and other nutritional indices, including total Kt/V, weekly creatinine clearance (CCr), residual glomerular filtration rate (GFR), protein nitrogen appearance (PNA), subjective global assessment (SGA), and serum albumin, were measured simultaneously. RESULTS: The mean age of the patients was 55.6 +/- 12.2 years, and the mean duration of dialysis was 33.6 +/- 28.5 months. The mean body mass index (BMI) was 22.7 +/- 3.7. The average LBM-AM was 43.6 +/- 8.0 kg; the average LBM-CK was 33.0 +/- 9.3 kg. The difference between the calculated LBM AM and LBM-CK was 10.7 kg, with LBM-AM always giving a higher value; the limits of agreement were -5.8 kg and 27.1 kg. The difference between the two measures correlated with residual GFR (Pearson r = 0.629, p < 0.001). After normalizing for desired body weight, LBM-AM was only modestly correlated with serum albumin level. No correlations were found between overall SGA score or normalized protein nitrogen appearance (nPNA) and LBM-AM or LBM-CK. CONCLUSIONS: In Chinese patients at least, a substantial discrepancy exists between LBM-AM and LBM-CK. The difference is especially marked in patients with significant residual renal function. The optimal method for determining LBM remains obscure in Chinese CAPD patients. Moreover, LBM correlated poorly with other nutritional indices. Multiple parameters should be taken into consideration in an assessment of nutritional status of CAPD patients. PMID- 11216565 TI - Is obesity a favorable prognostic factor in peritoneal dialysis patients? AB - OBJECTIVE: To determine the influence of an elevated body mass index (BMI) on cardiovascular outcomes and survival in peritoneal dialysis (PD) patients. DESIGN: Prospective, observational study of a prevalent PD cohort at a single center. SETTING: Tertiary care institutional dialysis center. PATIENTS: The study included all patients with a BMI of at least 20 who had been receiving PD for at least 1 month as of 31 January 1996 (n = 43). Patients were classified as overweight [BMI > 27.5; mean +/- standard error of mean (SEM): 32.1 +/- 1.1; n = 14] or normal weight (BMI 20-27.5; mean +/- SEM: 23.8 +/- 0.4; n = 29). OUTCOME MEASURES: Patient survival and adverse cardiovascular events (myocardial infarction, congestive cardiac failure, cerebrovascular accident, and symptomatic peripheral vascular disease) were recorded over a 3-year period. RESULTS: At baseline, no significant differences were seen between the groups in clinical, biochemical, nutritional, or echocardiographic parameters, except for a lower dietary protein intake (0.97 +/- 0.10 g/kg/day vs 1.44 +/- 0.10 g/kg/day, p = 0.004) and a higher proportion of well-nourished patients by subjective global assessment (100% vs 72%, p < 0.05) in the overweight group. After 3 years of follow-up, 29% of overweight patients and 69% of normal-weight patients had died (p < 0.05). Using a Cox proportional hazards model, a BMI greater than 27.5 was shown to be an independent positive predictor of patient survival, with an adjusted hazard ratio (HR) of 0.09 [95% confidence interval (CI): 0.01-0.85; p < 0.05]. However, being overweight did not significantly influence myocardial infarction-free survival (adjusted HR: 0.33; 95% CI: 0.07-1.48; p = 0.15) or combined adverse cardiovascular event-free survival (adjusted HR: 0.67; 95% CI: 0.23-1.93; p = 0.46). CONCLUSIONS: Obesity conferred a significant survival advantage in our PD population. Obese patients should therefore not be discouraged from receiving PD purely on the basis of BMI. Moreover, maintaining a higher-than-average BMI to preserve "nutritional reserve" may help to reduce the mortality and morbidity rates associated with PD. PMID- 11216566 TI - Chlamydia pneumoniae DNA in peripheral blood mononuclear cells in peritoneal dialysis patients. AB - OBJECTIVE: The aim of the present study was to examine the association between infection with Chlamydia pneumoniae and symptomatic atherosclerosis in peritoneal dialysis (PD) patients. DESIGN: Cross-sectional study. SETTING: Peritoneal Dialysis Unit of Kingston General Hospital. PATIENTS: Fifty-five prevalent PD patients. OUTCOME MEASURES: (1) Infection with C. pneumoniae diagnosed by detection of DNA in peripheral blood mononuclear cells (PBMCs) using polymerase chain reaction. (2) Symptomatic atherosclerosis involving the coronary, cerebral, or peripheral circulation. RESULTS: The DNA of C. pneumoniae was detected in PBMCs in 33 patients (60.0%). Atherosclerosis was present in 16 of 33 (48%) PBMC C. pneumoniae DNA-positive patients, and in 10 of 22 (45%) PBMC C. pneumoniae DNA negative patients (p = 0.83). Using multiple logistic regression and controlling for a number of known cardiovascular risk factors, PBMC C. pneumoniae DNA status was not predictive of atherosclerosis. The only significant independent predictors of atherosclerosis were diabetes and age. CONCLUSIONS: In prevalent PD patients, a high prevalence of symptomatic atherosclerosis and of Chlamydia pneumoniae DNA in PBMCs were seen; however, the results of the present study do not support the presence of an association between infection with C. pneumoniae and atherosclerosis. PMID- 11216567 TI - Evaluation of several saccharides as osmotic agent for peritoneal dialysate. AB - OBJECTIVE: The carbonyl group of glucose reacts non-enzymatically with the amino group of protein to form advanced glycosylation end-products (AGEs). AGEs are found in the peritoneum of continuous ambulatory peritoneal dialysis patients, and this AGE formation is suspected to be one of the causes of impaired peritoneal function. In order to control AGE formation in the peritoneum, AGE formation and ultrafiltration in rats were examined with peritoneal dialysates using as osmotic agents saccharides that lack a carbonyl group, the saccharic acid lactobionate [molecular weight (MW) 358.30], the sugar alcohol maltitol (MW 344.32), and the nonreducing sugar nistose (MW 666.58). DESIGN: Bovine serum albumin (BSA) (25 mg/mL) was incubated with 18, 36, and 72 mg/mL maltitol, lactobionate, nistose, and glucose at 37 degrees C. After 3 or 6 weeks, amounts of furosine and N-(carboxymethyl) lysine were measured. A 20-mL intraperitoneal injection of a lactate-based dialysate (osmotic pressure 388 mOsm/kg) containing 4.34% maltitol, 4.52% lactobionate, or 8.4% nistose was given to Sprague-Dawley rats and, after 2, 4, or 6 hours, the quantity of effluent and levels of urea nitrogen and creatinine in the effluent and in serum were measured. RESULTS: No increases in furosine or N-(carboxymethyl) lysine were seen with maltitol, lactobionate, or nistose after 3 and 6 weeks of incubation with BSA; AGE formation was not observed. In the study in rats, the quantity of abdominal fluid after a 6-hour dwell was nistose > lactobionate > maltitol > glucose. No differences in dialysate-to-plasma ratios for urea nitrogen or creatinine were seen in any group. CONCLUSIONS: AGE formation in peritoneal tissue might be controlled by using saccharides with a modified carbonyl group as osmotic agents for peritoneal dialysates. Nistose is considered to yield the most efficient dialysis. PMID- 11216568 TI - A comparison between 1.36% and 3.86% glucose dialysis solution for the assessment of peritoneal membrane function. AB - OBJECTIVE: To assess peritoneal membrane function with respect to fluid transport, parameters of low molecular weight solute transport, and estimations of the function of peritoneal water channels, comparing the results from a 1.36%/1.5% glucose solution with those from a 3.86%/4.25% solution in standardized peritoneal function tests. DESIGN: The study was performed in 40 stable continuous ambulatory peritoneal dialysis (CAPD) patients [median age 50 years (range: 22-74 years); duration of CAPD 9 months (range: 2-45 months)] who underwent two standard peritoneal permeability analyses (SPAs) within 1 month. One SPA used 1.36% glucose; the other, 3.86% glucose. Mass transfer area coefficients (MTACs) and dialysate-to-plasma (D/P) ratios were compared for the two solutions. Also, two different methods of estimating aquaporin-mediated water transport were compared: the sieving of sodium (3.86% glucose) and the difference in net ultrafiltration (deltaNUF), calculated as NUF 3.86% SPA - NUF 1.36% SPA. RESULTS: Median NUF in the 1.36% glucose SPA was -46 mL (range: -582 mL to 238 mL); in the 3.86% SPA, it was 554 mL (range: -274 mL to 1126 mL). The median difference in NUF for the two SPAs was 597 mL (range: 90-1320 mL). No difference between the two solutions was seen for the MTAC of creatinine (11.4 mL/min for 1.36% vs 12.0 mL/min for 3.86%) and absorption of glucose (64% vs 65%, respectively). Also, D/P creatinine was not different: 0.77 (1.36%) and 0.78 (3.86%). However, the ratio of dialysate glucose at 240 minutes and at 0 minutes (Dt/D0) was 0.34 (1.36%) and 0.24 (3.86%), p < 0.01. Values of D/P creatinine from the two glucose solutions were strongly correlated. The intra-individual differences were small and showed a random distribution. Patient transport category was minimally influenced by the tonicity of the dialysate. The minimum D/P Na+ (3.86%) was 0.884, and it was reached after 60 minutes. After correction for Na+ diffusion, D/P Na+ decreased to 0.849 after 120 minutes. The correlation coefficient between the diffusion-corrected D/P Na+ and the deltaNUF was 0.49, p < 0.01. An inverse relationship was present between MTAC creatinine and D/P Na+ (p < 0.01) This correlation can be explained by the rapid disappearance of the osmotic gradient owing to a large vascular surface area. Such a correlation was not present between MTAC creatinine and deltaNUF. CONCLUSIONS: We conclude that a standardized 4-hour peritoneal permeability test using 3.86%/4.25% glucose is the preferred method to assess peritoneal membrane function, including aquaporin mediated water transport. The D/P Na+ after correction for Na+ diffusion is probably more useful for the assessment of aquaporin-mediated water transport than is deltaNUF obtained with 3.86%/4.25% and 1.36%/1.5% glucose-based dialysis solutions. PMID- 11216570 TI - Characteristics of peripheral and peritoneal white blood cells in children with chronic renal failure, dialyzed or not. AB - OBJECTIVE: To explore further the mechanisms leading to immune deficiency in chronic renal failure and the role of dialysis treatment in these mechanisms. DESIGN: Cross-sectional and longitudinal analysis. PATIENTS: We studied 39 children treated with peritoneal dialysis (PD), 23 children treated with hemodialysis (HD), 33 children not yet dialyzed [chronic renal failure (CRF)], and 27 healthy children. Peritoneal cells were also obtained from PD children for analysis. METHODS: White blood cells (WBCs) were isolated from blood and peritoneal dialysis effluent by centrifugation. The number of CD2+, CD4+, and CD8+ T cells, B cells, and natural killer cells were measured by flow cytometry. RESULTS: The total peripheral blood lymphocyte count was lower in PD children (2.6 x 10(9)/L), HD children (2.1 x 10(9)/L), and CRF children (2.0 x 10(9)/L) compared with healthy children (3.1 x 10(9)/L, p < 0.05). The B lymphocyte count was also lower in PD children (0.34 x 10(9)/L), HD children (0.22 x 10(9)/L), and CRF children (0.33 x 10(9)/L) compared with healthy children (0.52 x 10(9)/L, p < 0.01). Numbers of CD4+ T cells were not different, but numbers of CD8+ T cells were lower in PD children (0.56 x 10(9)/L), HD children (0.63 x 10(9)/L), and CRF children (0.53 x 10(9)/L) compared with healthy children (0.77 x 10(9)/L, p < 0.05). The count of natural killer cells was lower in PD children (0.21 x 10(9)/L), HD children (0.17 x 10(9)/L), and CRF children (0.18 x 10(9)/L) compared with healthy children (0.50 x 10(9)/L, p < 0.0001). The CD4/CD8 ratio of lymphocytes in peritoneal effluent was 0.8 versus 1.9 in peripheral blood (p < 0.001). The CD2/CD19 ratio was not different. The cell subsets remained stable during the first year of PD treatment. The CD2/CD19 ratio in peritoneal effluent was higher in children with a peritonitis incidence > or = 1 per year. CONCLUSIONS: The reduced numbers of B lymphocytes, CD8+ T cells, and natural killer cells found in CRF children, dialyzed or not, may favor the frequent occurrence of infections. PMID- 11216569 TI - Icodextrin effluent leads to a greater proliferation than glucose effluent of human mesothelial cells studied ex vivo. AB - OBJECTIVE: To compare the effect of glucose (Glu) and icodextrin (Ico) dialysate on in vitro culture of mesothelial cells (MC) from peritoneal dialysis (PD) patients. DESIGN: Prospective, controlled comparative study on the effects of two PD solutions. SETTING: A tertiary-care public university hospital. PATIENTS: Sixteen PD patients regularly using Glu dialysate were asked to collect an 8-hour dwell peritoneal effluent on 2 different days, with an interval shorter than 7 days. In the first collection, 2.27% Glu solution and in the last, 7.5% Ico solution was infused. Human MC were isolated from the nocturnal peritoneal effluent bags and grown ex vivo. MAIN OUTCOME MEASURES: Mesothelial cell proliferative capacity ex vivo. RESULTS: Mesothelial cells were present in all patient dialysates except that of a single patient's Glu dialysate. The number of MC drained was similar with both solutions. After the initial culture reached confluence, MC were identified in 14 and 12 patients receiving Ico and Glu, respectively. However, in 1 patient using Ico and in 2 using Glu, the MC count at this stage was so low that further subculture could not be performed. Cells from Ico-derived solutions exhibited a higher degree of proliferation than cells from Glu-derived solutions. The morphology of MC was also different. Cells from drained effluent were typical in 11 patients using Glu solution in contrast with 14 patients using Ico. At confluence, the percentages of typical appearance were 50% and 92.9% (p < 0.05) in Glu and Ico respectively. CONCLUSIONS: Mesothelial cells taken from icodextrin effluent show a greater proliferation ex vivo than those taken from glucose effluent. PMID- 11216571 TI - A laparoscopic approach under local anesthesia for peritoneal dialysis access. AB - OBJECTIVE: Presented herein is a technical description of a time-proven laparoscopic approach to establishing successful long-term peritoneal dialysis access. DESIGN: Using a two-port technique, the peritoneal catheter is inserted through a paramedian port site while continuously monitoring the implant procedure with a laparoscope from a second port location. A long rectus sheath tunnel created with a nontrocar port device keeps the dialysis catheter oriented toward the pelvis. Helium abdominal insufflation enables full surgical laparoscopy under local anesthesia. Validation of the effectiveness of the technique is made by comparison to previous implantation experience using an open dissection method. PATIENTS: Laparoscopic implantation of peritoneal catheters was performed in 150 patients, and placement by open dissection was accomplished in 63 patients. MAIN OUTCOME MEASURE: The incidence of complications and revision free catheter survival between implantation methods were compared. RESULTS: Catheters implanted laparoscopically had a significantly lower incidence of flow dysfunction (p < 0.05) and better survival (p < 0.001) than those placed by open dissection. CONCLUSIONS: Compared to implantation by open dissection, the laparoscopic approach provides the patient reduced perioperative discomfort. The procedure can be performed safely with the patient under local anesthesia on an ambulatory basis. Laparoscopic implantation significantly reduces the incidence of catheter flow dysfunction and permits simultaneous identification and correction of other problems that could complicate dialysis therapy. PMID- 11216572 TI - Peritoneal homocysteine clearance is inefficient in peritoneal dialysis patients. AB - OBJECTIVES: To investigate the degree and the determinants of peritoneal homocysteine (Hcy) clearance and to compare measured Hcy clearance with the Hcy clearance predicted based on molecular weight (MW). DESIGN: Cross-sectional observational analysis. SETTING: Tertiary care institutional dialysis center. PATIENTS: Sixty-five stable peritoneal dialysis (PD) patients. OUTCOME MEASURES: Fasting blood and 24-hour pooled dialysate effluents were collected for determination of peritoneal clearances of Hcy (CpHcy), urea (CpUr), and creatinine (CpCr). The dialysate-to-plasma creatinine ratio at 4 hours (D/P Cr 4 h) and levels of red cell folate, B12, ferritin, and C-reactive protein (CRP) were measured concurrently. Observed CpHcy was compared with predicted clearance, based on Hcy plasma protein binding and the relative molecular weights of Hcy, urea, and creatinine. RESULTS: Plasma concentrations of Hcy averaged 24.6 +/- 1.1 micromol/L and were elevated above the upper limit of normal in 59 (91%) patients. The mean dialysate concentration of Hcy was 2.9 +/- 0.3 micromol/L, equating to a daily peritoneal elimination of 34.6 +/- 3.6 micromol. Observed CpHcy was closely approximated by predicted CpHcy (8.7 +/- 0.6 L/week/1.73 m2 vs 9.0 +/- 0.3 L/week/1.73 m2 respectively, p = 0.55). Patients maintained on automated PD (n = 5) had a CpHcy similar to that of patients treated with continuous ambulatory peritoneal dialysis (8.9 +/- 1.0 L/week/1.73 m2 vs 8.7 +/- 0.6 L/week/1.73 m2, p = 0.92). The CpHcy was significantly correlated with C reactive protein (CRP), D/P creatinine, CpUr, CpCr, and peritoneal protein loss, but not with plasma Hcy, albumin, B12, ferritin, age, dialysis duration, peritonitis episodes, or daily dialysate effluent volume. By multivariate analysis, the only variables that remained significant independent predictors of CpHcy were CRP and D/P Cr 4 h. High and high-average transporters had a higher CpHcy than low and low-average transporters (9.7 +/- 0.8 L/week/1.73 m2 vs 7.0 +/ 0.7 L/week/1.73 m2, p < 0.05), despite comparably elevated plasma Hcy concentrations [25.2 +/- 1.5 micromol/L vs 23.4 +/- 1.6 micromol/L, p = nonsignificant (NS)]. CONCLUSIONS: Elevated plasma concentrations of Hcy are not efficiently reduced by PD. The relatively low peritoneal clearance of Hcy is largely accounted for by a high degree of plasma protein binding and is significantly influenced by peritoneal membrane permeability. PMID- 11216573 TI - Human peritoneal mesothelial cells produce nitric oxide: induction by cytokines. AB - OBJECTIVE: To investigate the induction of nitric oxide synthase type II (iNOS) in human peritoneal mesothelial cells (HPMC) using cytokines and bacterial lipopolysaccharide (LPS). DESIGN: Confluent monolayers of HPMC were exposed to cytokines [tumor necrosis factor alpha (TNFalpha), interleukin-1 beta (IL-1beta), interferon gamma (IFNgamma)] or LPS, individually or in various double and triple combinations, for 24-72 hours. Concentrations of nitrate and nitrite in the media were quantified using the Griess reaction and used as indirect indices of nitric oxide (NO) production. The expression of iNOS was assessed using reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot. RESULTS: Neither single cytokines nor LPS was able to induce iNOS mRNA or NO production. Both double combinations of TNFalpha + IFNgamma and IL-1beta + IFNgamma were able to induce iNOS mRNA expression, but only TNFalpha + IFNgamma induced significant NO production. The triple combination of TNFalpha + IFNgamma + IL-1beta induced even more NO production than TNFalpha + IFNgamma. There was no constitutive NO synthase type III (eNOS) expression in HPMC. CONCLUSIONS: Certain combinations of cytokines could stimulate cultured HPMC to produce NO, and HPMC might be a source of intraperitoneal NO production during peritonitis. PMID- 11216575 TI - The effect of hemodialysis during break-in period on residual renal function in CAPD patients. PMID- 11216574 TI - Thrombin suppresses matrix metalloproteinase 2 activity and increases tissue inhibitor of metalloproteinase 1 synthesis in cultured human peritoneal mesothelial cells. AB - OBJECTIVE: Recently, high levels of intraperitoneally generated thrombin were found in the effluent of patients treated with continuous ambulatory peritoneal dialysis (CAPD). The aim of the present study was to investigate in human peritoneal mesothelial cells (HMCs) the effect of thrombin on the activity and synthesis of matrix metalloproteinases (MMPs), which regulate the degradation of basement membrane collagen. METHODS: Cultured HMCs were isolated from omental tissue and used at confluence for the experiments. Conditioned media were obtained by incubating cells with serum-free M199 containing the relevant doses of thrombin. Activity of MMP-2 and MMP-9 were determined by an activity assay system. The antigen levels of MMPs and of the specific tissue inhibitor of metalloproteinases 1 (TIMP-1) were measured by ELISA. Northern blot analysis was applied to analyze mRNA expression of MMP-2 and TIMP-1. RESULTS: Incubation of HMCs with increasing doses of thrombin resulted in a concentration- and time dependent suppression of MMP-2 activity. No changes in MMP-9 activity were seen. After a 48-hour stimulation period with thrombin (5 U/mL), MMP-2 activity decreased to 53% of that seen in control conditions. Antigen measurements revealed that this decrease was paralleled by a slight reduction in MMP-2 levels, which became significant at a thrombin dose of 5 U/mL [50.65 +/- 7.5 ng/10(5) cells (48 hours, 5 U/mL) vs 64.6 +/- 10.1 ng/10(5) cells (control)]. Under the same conditions, TIMP-1 levels were considerably increased [3.9 +/- 0.46 microg/10(5) cells (48 hours, 5 U/mL) vs 1.2 +/- 0.14 microg/10(5) cells (control)]. Hirudin (10 U/mL) completely inhibited the thrombin-induced effects on MMP-2 and TIMP-1 synthesis. These results were also reflected by Northern blot hybridization, where a slight decrease in MMP-2 and an increase in TIMP-1 mRNA expression were observed in response to thrombin. CONCLUSIONS: Our results suggest that high thrombin levels suppress MMP-2 activity through decreased MMP-2 and increased TIMP-1 synthesis. Thus, thrombin may promote the accumulation of basement membrane collagen. In addition to fibrin formation, this mechanism may represent a further contribution by thrombin to peritoneal thickening during CAPD. PMID- 11216576 TI - Pruritus and anemia in a patient on peritoneal dialysis--pitfalls in diagnosis for common symptoms. PMID- 11216577 TI - Gastrointestinal transit of an indigestible solid in patients on CAPD. PMID- 11216578 TI - Early postoperative complications of removal of Tenckhoff peritoneal dialysis catheter. PMID- 11216579 TI - Practical aspects of the addition of sodium bicarbonate to peritoneal dialysate. PMID- 11216580 TI - Campylobacter jejuni bacteremia, peritonitis, and exacerbation of chronic pancreatitis in a patient on CAPD: case report and literature review. PMID- 11216581 TI - Reduced 1,2-dicarbonyl compounds in bicarbonate/lactate-buffered peritoneal dialysis (PD) fluids and PD fluids based on glucose polymers or amino acids. PMID- 11216583 TI - Short-term efficacy of tacrolimus ointment in severe uremic pruritus. PMID- 11216582 TI - Spontaneous VEGF production by cultured peritoneal mesothelial cells from patients on peritoneal dialysis. PMID- 11216584 TI - Intensive continuous peritoneal dialysis as treatment of uremic pericarditis. PMID- 11216585 TI - Rate of decline in residual renal fuction is equal in CAPD and automated peritoneal dialysis patients. PMID- 11216586 TI - Endoluminal brush for clearing peritoneal dialysis catheter obstruction. PMID- 11216588 TI - Prolonged periodic intra-abdominal bleeding without serious consequences in a female patient on CAPD. PMID- 11216587 TI - Shigella sonnei peritonitis in a patient on CAPD. PMID- 11216589 TI - Tuberculin and anergy testing in CAPD patients. PMID- 11216590 TI - Uremic anorexia: a consequence of persistently high brain serotonin levels? The tryptophan/serotonin disorder hypothesis. AB - Anorexia is a frequent part of uremic syndrome, contributing to malnutrition in dialysis patients. Many factors have been suggested as responsible for uremic anorexia. In this paper we formulate a new hypothesis to explain the appetite disorders in dialysis patients: "the tryptophan/serotonin disorder hypothesis." We review current knowledge of normal hunger-satiety cycle control and the disorders described in uremic patients. There are four phases in food intake regulation: (1) the gastric phase, during which food induces satiety through gastric distention and satiety peptide release; (2) the post absorptive phase, during which circulating compounds, including glucose and amino acids, cause satiety by hepatic receptors via the vagus nerve; (3) the hepatic phase, during which adenosine triphosphate (ATP) concentration is the main stimulus inducing hunger or satiety, with cytokines inhibiting ATP production; and (4) the central phase, during which appetite is regulated through peripheral (circulating plasma substances and neurotransmitters) and brain stimuli. Brain serotonin is the final target for peripheral mechanisms controlling appetite. High brain serotonin levels and a lower serotonin/dopamine ratio cause anorexia. Plasma and brain amino acid concentrations are recognized factors involved in neurotransmitter synthesis and appetite control. Tryptophan is the substrate of serotonin synthesis. High plasma levels of anorectics such as tryptophan (plasma and brain), cholecystokinin, tumor necrosis factor alpha, interleukin-1, and leptin, and deficiencies of nitric oxide and neuropeptide Y have been described in uremia; all increase intracerebral serotonin. We suggest that brain serotonin hyperproduction due to a uremic-dependent excess of tryptophan may be the final common pathway involved in the genesis of uremic anorexia. Various methods of ameliorating anorexia by decreasing the central effects of serotonin are proposed. PMID- 11216592 TI - Literature: November-December 2000. PMID- 11216591 TI - Intermittent severe abdominal pain with normal peritoneal fluid findings on presentation. PMID- 11216593 TI - Fever in infants and children. PMID- 11216594 TI - What's new with enteroviral infections? PMID- 11216596 TI - Bibliography. Current world literature. Orthopedics. PMID- 11216595 TI - Bibliography. Current world literature. Hematology and oncology. PMID- 11216597 TI - Bibliography. Current world literature. Infectious diseases. PMID- 11216598 TI - The nasomaxillary retractor: a new method to prevent nasoendotracheal tube and vascular injury. PMID- 11216599 TI - The lateral osteotomy in rhinoplasty. PMID- 11216600 TI - Silastic implants for temporomandibular joint disorders. PMID- 11216601 TI - Breast reconstruction using a deepithelialized rectus abdominis musculocutaneous flap. AB - There are many methods for breast reconstruction. Using implants can achieve good results without conspicuous scarring, but this method has disadvantages, such as infection, exposure, and capsular contracture. The rectus abdominis musculocutaneous (RAM) flap has become a standard technique because of its safety and abundant volume, but its main problem is the lack of a color and texture match between the skin paddle and the skin around the flap. To overcome such shortcomings, the authors perform breast reconstruction using tissue expansion and a RAM flap. First a tissue expander is inserted superficially to the pectoralis major muscle at the time of or after mastectomy, and is expanded to a size larger than the contralateral breast. The expander is replaced with the deepithelialized RAM flap. Scar revision is performed if the expander is inflated satisfactorily. The authors used this technique in 11 patients and obtained good results without severe complications. PMID- 11216602 TI - Lower extremity salvage using a free flap associated with the Ilizarov method in patients with massive combat injuries. AB - Nine patients with massive combat injuries of the lower extremities were treated with Ilizarov bone transport in conjunction with free muscle flap coverage. In 4 patients soft-tissue coverage was applied first, and distraction osteogenesis was initiated 4 to 6 weeks later. In 3 patients both methods were applied simultaneously, and in 2 patients soft-tissue coverage occurred after distraction. The bones healed well, and all flaps survived. The segmental defects ranged from 8 to 16.5 cm in greatest dimension. The total disability time from initial injury ranged from 16 to 25.5 months. In all patients, full union of the tibia was achieved, and no osteomyelitis occurred. However, in 2 patients the applied flap became depressed, necessitating another flap operation. Despite late treatment in all 9 patients, successful results were obtained. Maintaining the original length of the tibia and providing timely, definitive treatment offer the best outcome for repair of massive injuries of the lower extremities. The Ilizarov transport method, used in combination with muscle flap coverage, represents an effective therapy for repair of massive injury of the lower extremities. PMID- 11216603 TI - One-stage emergency treatment of open grade IIIB tibial shaft fractures with bone loss. AB - The purpose of this study was to report the authors' experience with emergency reconstruction of severe tibial shaft fractures. Five male patients were admitted to the emergency room with a grade IIIB open tibial shaft fracture with bone loss (average age, 33 years; age range, 18-65 years). Injuries were the result of motorcycle accidents (N = 2), pedestrian accidents (N = 1), gunshot wound (N = 1), and paragliding fall (N = 1). Primary emergent one-stage management for all patients consisted of administration of antibiotics, debridement, stabilization by locked intramedullary nailing, bone grafting from the iliac crest, and coverage using free muscle flaps (four latissimus dorsi and one gracilis). The average follow-up was 21 months (range, 8 months-3.5 years). Partial weight bearing with no immobilization was started at 3 months, and full weight bearing began 5 months after trauma. No angular complications and no nonunions were observed. There was one case of superficial infection without osteitis. All fractures healed within 6 months in 4 patients and within 10 months in 1 patient. At the last follow-up examination, ankle and knee motion was normal and no pain was noted, except for 1 patient who had associated lesions (ankle motion reduced by 50%). Aggressive emergency management of severe open tibial fractures provides good results. It improves end results markedly, not only by reducing tissue loss from infection, but also reducing healing and rehabilitation times. PMID- 11216604 TI - Hand elevation: a new test for carpal tunnel syndrome. AB - Hand elevation can reproduce the symptoms of carpal tunnel syndrome. This phenomenon prompted the idea of developing a simple hand elevation test to diagnose carpal tunnel syndrome. A total of 200 hands in 118 patients diagnosed with carpal tunnel syndrome were tested prospectively from September 6, 1999, to February 3, 2000. Three provocative tests (hand elevation test, Phalen's test, and Tinel's test) were performed on each hand for both the experimental group (200 hands) and the control group (200 hands). McNemar chi-squared analysis was used to compare the sensitivity and specificity of the new hand elevation test with those of Phalen's test and Tinel's test. The sensitivity and specificity of the hand elevation test is 75.5% and 98.5% respectively. Phalen's test had 67.5% sensitivity and 91.0% specificity. Tinel's test had 67.5% sensitivity and 90.0% specificity. The difference in sensitivities between the hand elevation test and Phalen's test was significant (p = 0.05). No significant difference was found in the sensitivity between the hand elevation test and Tinel's test. The comparison of specificity of the hand elevation test and Phalen's test was significant (p = 0.001). Significance was also observed in specificity between the hand elevation test and Tinel's test (p = 0.001). In this study, the sensitivity and specificity of the elevation test were higher than those of Phalen's test and Tinel's test. Statistical analysis confirms the eligibility of the hand elevation test as a useful, provocative test. PMID- 11216605 TI - Severe, traumatic soft-tissue loss in the antecubital fossa and proximal forearm associated with radial and/or median nerve palsy: nerve recovery after coverage with a pedicled latissimus dorsi muscle flap. AB - A total of 6 patients with complex, traumatic wounds of the antecubital fossa and proximal forearm were included in this study. All patients presented with radial and/or median nerve palsies in addition to their soft-tissue defect. Except for 1 patient with a 15-cm defect of the radial nerve, all other traumatized nerves appeared in-continuity at the time of surgery. However, the nerve injury was severe enough to induce Wallerian degeneration (i.e., axonotmesis in traumatized nerves in-continuity). Three patients required brachial artery reconstruction with a reverse saphenous vein graft. Wound coverage was accomplished using a pedicled latissimus dorsi muscle flap, which was covered with a split-thickness skin graft. Successful reconstruction was obtained in all patients. Follow-up ranged from 2 to 6 years. The range of motion at the elbow and forearm was considered excellent in 5 patients and good in the remaining patient who had an intra-articular fracture. Motor recovery of traumatized nerves in-continuity was observed in all but 1 patient who had persistent partial anterior interosseous nerve palsy. The grip strength of the injured hand measured 70% to 85% of the contralateral uninjured hand. Median nerve sensory recovery was excellent in all patients. The versatility of the pedicled latissimus dorsi muscle flap for coverage of these complex wounds with traumatized neurovascular bundles around the elbow is discussed. PMID- 11216606 TI - Triangular mattress suture in abdominal diastasis to prevent epigastric bulging. AB - In the classic abdominoplasty, the treatment of large diastasis recti with simple or vertical mattress sutures may result in a nonaesthetic bulge. The surgeon may produce a craniocaudal bulge deformity by treating the flaccidity in the horizontal plane only, although it occurs in all directions. The authors describe the triangular mattress suture for the treatment of large diastasis recti, and demonstrate the mechanism involved in producing an epigastric bulge. Also presented is their clinical experience with 56 patients, with a 3-year follow-up, using this new plication method. The triangular mattress suture is a simple, quick, and effective way to correct abdominal diastasis and to avoid the epigastric bulge deformity with no added morbidity. PMID- 11216607 TI - A new surgical treatment of keloid: keloid core excision. AB - Keloids and hypertrophic scars result from excessive collagen deposition, the cause of which is not yet known. Unlike hypertrophic scars, keloids frequently persist at the site of injury, often recur after excision and always overgrow the boundaries of the original wound. There have been many trials to control keloids, but most of them have been unsuccessful. The authors propose a new surgical technique to treat keloids and name it keloid core extirpation. They excise the inner fibrous core from the keloid and cover the defect with a keloid rind flap, which is arterialized by the subcapsular vascular plexus. The authors treated 24 keloids of the ear, trunk, face, and genitalia with keloid core excision. Four cases of partial rind flap congestion or necrosis occurred. Those patients who healed primarily after surgery showed no evidence of keloid recurrence as long as they were followed. The authors have found the keloid core extirpation technique to be excellent in preventing keloid recurrence, with no adjuvant therapy after surgery. PMID- 11216608 TI - Could ionizing radiation forestall cauliflower ear? AB - Repeated trauma to the ear very often results in "cauliflower ear." Many methods have been suggested to prevent an injured ear from demonstrating a cauliflowerlike deformity. The principles of treatment are evacuation of the hematoma, control of the reaccumulation of fluid, and maintenance of the cartilage contour. The authors studied the effect of ionizing radiation on deformed rabbit ears induced by repeated trauma. Twenty ears (10 rabbits) were used in the experiment. The animals were divided into four groups (control, preradiation, low dose, and high dose). Hematoma was produced by pounding the lateral side of the auricle 10 times with a 50-g weight at a height of 15 cm. The thickness of the injured and uninjured sites was measured, and histological analysis was performed for each group. The thickness of the ears of the irradiated groups was significantly less than the control group. The authors think that radiation treatment of repeatedly injured ears could prevent ear deformity, and could possibly be an adjunctive form of management of cauliflower ear in addition to hematoma evacuation and compression therapy. PMID- 11216609 TI - Dermal fibroblasts do not enhance the graft take rate of autologous, cultured keratinocyte suspension on full-thickness wounds in rats. AB - Dermal fibroblasts are known to play an important role in wound healing. In this study, cultured autologous keratinocyte suspension was applied with fibrin glue to the full-thickness wounds in rats (N = 20). Histological analysis on day 14 showed regenerated epithelium in 10 wounds (50%). Keratinocytes were also premixed with allogeneic dermal fibroblasts in a ratio of 3:1 and 5:1 before application to other full-thickness wounds (N = 20) with fibrin glue. Regeneration of epithelium was observed in 10 (50%) and 9 (45%) wounds respectively. Acute inflammatory reaction and mild to moderate proliferation of fibroblasts in the subepithelial layer of the allogeneic fibroblasts were noted. The addition of dermal fibroblasts to keratinocytes/fibrin glue does not enhance the take rate of the cultured keratinocyte suspension. PMID- 11216610 TI - Botfly myiasis: case report and brief review. AB - The painful, boil-like lesion of furuncular myiasis is a result of the invasion of subcutaneous tissues by larvae of Dermatobia hominis, the human botfly. This arthropod is indigenous to Mexico, and Central and South America, and imported cases to the United States are increasing as travel to these regions continues to rise. There are several dozen reports of furuncular myiasis in the United States and Canadian literature since the initial description of this disease in 1920. None of the reports are in the surgical literature, which is surprising because the treatment of choice is surgical excision. Surgical removal sometimes results in damage to the larva with retention of larval fragments in the wound. The authors describe a patient and a novel approach that ensures removal of the intact larva and its surrounding burrow. PMID- 11216611 TI - Munchausen syndrome. AB - Munchausen syndrome is a rare condition in which the patient repeatedly seeks medical care for factitious illnesses. With this self-inflicted disease, the patients characteristically travel from one hospital to another, feigning acute, usually spectacular illnesses. The patients willingly submit themselves to extensive as well as invasive diagnostic and therapeutic procedures. Munchausen syndrome is a psychiatric disorder that requires psychiatric treatment. Reconstructive surgical procedures may be required to correct the acquired deformities. The difficulty in Munchausen syndrome lies essentially in early recognition of the psychiatric syndrome. Two exceptional cases are reported, and diagnosis and treatment are presented in the light of the current literature. PMID- 11216612 TI - Life-threatening bleeding in a facial fracture. AB - Life-threatening bleeding in facial fractures is considered rare, and most reports do not recommend a precise treatment guideline. Although various methods have been suggested, they are unpredictable in efficacy and may lead to irreversible shock. To avoid irreversible shock, early detection and correct, effective treatment are mandatory. The authors report a patient who presented with a complex midface fracture after falling on June 23, 1999. Life-threatening oronasal bleeding developed 1 hour after arriving at the emergency room. Initial nasal packing failed to stop the nasal bleeding. After resuscitation, the patient's vital signs were stable but bleeding persisted. Angiography showed diffuse extravasation of contrast medium over the territory of the right internal maxillary artery. Embolization was performed successfully to stop the bleeding. The authors review the literature regarding the incidence, diagnosis, and treatment of life-threatening facial fracture. In the literature, the lack of a precise definition leads to various results by various treatments. The authors have formulated a succinct treatment guideline. They favor angiographic embolization as the first choice of treatment when tight nasal and/or oral packing fails. PMID- 11216613 TI - Bilateral breast reconstruction with the latissimus dorsi musculocutaneous flap: the importance of patient positioning. AB - This report of 2 patients demonstrates that bilateral breast reconstruction with the latissimus dorsi musculocutaneous flap is facilitated by simultaneous elevation of the flaps in the prone position and simultaneous insetting of the flaps in the supine position. Operative time, blood loss, and position changes are minimized using this technique. PMID- 11216614 TI - Replantation and triple expansion of a three-piece total scalp avulsion: six-year follow-up. AB - Total scalp avulsion in three scalp segments is an unusual injury. The authors describe the replantation of three scalp segments in a 15-year-old girl. Replantation of the middle scalp piece was unsuccessful, but a satisfactory aesthetic and functional result was obtained by expanding the same replanted tissue three times. Every effort should be undertaken to save the avulsed scalp, even in a severely damaged situation. PMID- 11216615 TI - Hydatid cyst in the soft tissue of the face without any primary. AB - Hydatid cyst of the subcutaneous tissue is rare, and often presents as a simple soft-tissue mass. A case of primary subcutaneous hydatid disease arising in the malar region is reported. Histopathological examination revealed the characteristic findings, which are consistent with soft-tissue hydatid disease. There was no sign of echinococcal involvement of organs other than the soft tissue of the face. To the authors' knowledge, this is the first reported case of a primary subcutaneous hydatid cyst arising in the skin in the absence of internal involvement. The patient remains disease free 14 months after surgery. The authors present their clinical findings, diagnostic techniques, and treatment of the patient, and review the literature. PMID- 11216616 TI - Calcific myonecrosis: case report and review. AB - Although a rare diagnosis, with few reports in the literature, calcific myonecrosis is a diagnosis that must be entertained in individuals presenting with expanding masses in the muscle compartments occurring years after an initial injury. The authors report a previously healthy 66-year-old man with an expanding right lower extremity mass felt initially to be an abscess. Despite presumably appropriate antimicrobial therapy, the lesion continued to expand, causing pain and loss of function. The patient subsequently underwent extensive debridement and free muscle flap transfer with an excellent outcome. This patient serves to remind us that, although calcific myonecrosis is an uncommonly encountered condition, it must be maintained in the differential diagnosis of an expanding muscle compartment mass. PMID- 11216617 TI - Nasal angiocentric lymphoma: an entity that should be remembered. AB - After four nasal aesthetic functional surgeries in a period of 18 months, a 46 year-old woman was evaluated who presented with moderate functional alteration, saddle-nose deformity, and total loss of the septal cartilage. Four months before presentation the patient sustained severe nasal trauma, resulting in depression of the nasal bridge without loss of function. Her problem was diagnosed initially as a consequence of an infected septal hematoma and loss of the septal cartilage. Based on this diagnosis, the patient was subjected, in an 18-month period, to four reconstructive surgeries by different specialists, without any improvement and with worsening of clinical presentation. During the authors' physical examination of the patient, she demonstrated marked nasal cutaneous retraction, atrophic nasal conchae with total loss of the septal cartilage, and a large loss of septal bone. Three nasal mucosa biopsies were acquired and the authors proceeded to carry out complete nasal reconstruction using external cranial table and rib cartilage. Histopathologically, a lesion was noted that was compatible with angiocentric lymphoma, for which treatment was administered according to this type of illness. The authors point out the importance of establishing an adequate diagnosis in the face of an apparently obvious clinical case, present cross-disciplinary treatment, and discuss the study protocol that should be used for this type of pathology. They present their reconstructive technique of the nasal structure using a combination of bone tissue and cartilage, the results, and the current state of the patient. PMID- 11216618 TI - The digital pulp as a presenting site of metastatic esophageal carcinoma. AB - An unusual skin lesion may be a primary skin cancer or a sign of internal malignancy. Metastatic lesions to the hand are rare. The authors describe a patient who presented with a nodule of the digital pulp. Workup, including X-ray films and biopsy, revealed a metastatic squamous cell carcinoma invading the distal phalanx. The primary site of the tumor was the esophagus. To the best of their knowledge, this is the second case described in the literature of a metastatic carcinoma of the esophagus presenting as a lesion of the digital pulp. PMID- 11216619 TI - Expanded applications for octyl-2-cyanoacrylate as a tissue adhesive. AB - The commercial introduction of octyl-2-cyanoacrylate as a medical-grade tissue adhesive was intended to be a rapid, painless, suture-free method for closure of simple lacerations and surgical wounds. The efficiency and therefore potential economic advantage of this material has led to further investigations of other possible indications. This glue has now been used in more than 100 different occasions for "off-label" applications including nailbed repair, skin graft fixation, temporary otoplasty, wound sealant, and other forms of wound closure. Complications are virtually nonexistent, and there has been no evidence of histotoxicity. The role of this material as an important reconstructive tool has not yet been delineated completely, but it appears to have no contraindications if used sensibly. PMID- 11216620 TI - A Cinderella story. PMID- 11216621 TI - Re: invited discussion. Role of three-dimensional computed tomography in the asessment of nasoorbitoethmoidal fractures. PMID- 11216622 TI - Reply: increased axonal regeneration through a biodegradable amnionic tube nerve conduit. PMID- 11216623 TI - Re: granular cell tumors in a child's finger. PMID- 11216624 TI - The legacy of Icarus in the 21st century: report of a case of aggressive submental basal cell carcinoma resulting from frequent use of a metallic ultraviolet reflector. PMID- 11216625 TI - Reversed skin island fascial pedicle flap of the posterior calf for distal defects of the leg and foot: an alternative for free flap transfer. PMID- 11216626 TI - An idea for umbilicus reconstruction. PMID- 11216627 TI - Subcutaneous emphysema of the eyelid and orbital cone after maxillary fracture. PMID- 11216628 TI - A ganglionic cyst in the axilla. PMID- 11216629 TI - Superficial scalp necrosis after replantation. PMID- 11216630 TI - A case of Merkel cell carcinoma with extension into the orbital cavity. PMID- 11216631 TI - The use of hyperbaric oxygen in treating meningococcemic skin necrosis. PMID- 11216632 TI - Ultrastructural anatomy of contracted capsules around textured implants in augmented breasts. AB - The development of a capsule around an implant is part of the physiological response to a foreign body. Capsular contracture is the most specific and frustrating complication of augmentation mammaplasty, and a lot of studies have been devoted to it. The aim of the current study is to examine the fine architecture of the contracted capsule around textured implants in humans. Eight capsules from augmented and contracted breasts with gel-filled, textured-surface silicone implants were studied after standard preparation for light and scanning electron microscopy, and after partial digestion in sodium hydroxide. Two capsules from contracted breasts around smooth implants and two noncontracted capsules around textured implants were prepared and studied in the same fashion as controls. A multilayer structure of the contracted capsule was seen, and the architecture of the various layers is described. The inner surface presents irregular craterlike depressions. The arrangement of collagen fibers varies in capsule layers. The effect of a textured-surface implant on the mechanism of capsule contraction based on the observed capsular architecture is that only part of the capsule is effective mechanically in producing a contracting force. A thin vascular layer was identified near the inner surface in contracted capsules around textured implants, and the authors' think that this layer is probably the key structure in the histological development and growth of the capsule. PMID- 11216633 TI - Focal adhesion kinases: interest in immunoendocrinology, developmental biology, and cancer. AB - The research field on focal adhesion-related kinases started a decade ago, but the term focal adhesion was introduced for the first time nearly 20 yr before. Since its identification, many studies have enlightened the role of the first intermediate of focal adhesion-related signals in a large number of biologic and physiologic processes. In this review, we try to integrate the most recent data about the known focal adhesion-related kinases, and we focus on three topics in which they deserve great interest: neuroendocrine-immune interactions, developmental biology, and proliferative diseases. PMID- 11216634 TI - Growth hormone: roles in male reproduction. AB - Growth hormone (GH), as its name suggests, is obligatory for growth and development. It is, however, also required for sexual differentiation and pubertal maturation and participates in gonadal steroidogenesis and gametogenesis. These roles are likely to reflect the endocrine actions of pituitary GH, directly at gonadal sites and indirectly via hepatic insulin-like growth factor-1. However, because GH is also produced in gonadal tissues, it may act in paracrine or autocrine ways to regulate local processes that are strategically regulated by pituitary GH. The concept that GH is a major regulator of male reproduction is the focus of this review. PMID- 11216636 TI - Large and asymptomatic pancreatic islet cell tumor in a patient with multiple endocrine neoplasia type 1. AB - The major phenotypes of multiple endocrine neoplasia type 1 (MEN 1) consist of three lesions characterized by hyperparathyroidism, pituitary tumors, and endocrine pancreatic tumors. The endocrine pancreatic tumors are a significant cause of disease-related mortality in MEN 1. Although symptomatic pancreatic tumors such as insulinoma and gastrinoma should be resected, the management of asymptomatic pancreatic tumors is not established. In asymptomatic pancreatic tumors, the most important factor is the propensity for malignant transformation of the tumors. Although there are no means to foresee it, the size of the pancreatic tumors might be predictive of malignant development in MEN 1. We report here a patient with MEN 1 who had a large asymptomatic pancreatic tumor. The patient (72-yr-old man) was diagnosed with primary hyperparathyroidism and underwent a total parathyroidectomy. Genetic examination showed a germline mutation of the MEN1 gene (E45G). Abdominal magnetic resonance imaging revealed a large (>6 cm) tumor with a heterogeneous pattern in the tail of the pancreas. No metastases of the tumor were evident. Serum levels of insulin, gastrin, and glucagon were normal, and the patient had no symptoms. Operative resection was performed, and microscopic examination revealed that the tumor was an islet cell tumor stained with multiple hormones. This is a case indicating that asymptomatic pancreatic tumors associated with MEN 1 might be indolent independent of their size. PMID- 11216635 TI - Localized calcium influx in pancreatic beta-cells: its significance for Ca2+ dependent insulin secretion from the islets of Langerhans. AB - Ca2+ influx through voltage-dependent Ca2+ channels plays a crucial role in stimulus-secretion coupling in pancreatic islet beta-cells. Molecular and physiologic studies have identified multiple Ca2+ channel subtypes in rodent islets and insulin-secreting cell lines. The differential targeting of Ca2+ channel subtypes to the vicinity of the insulin secretory apparatus is likely to account for their selective coupling to glucose-dependent insulin secretion. In this article, I review these studies. In addition, I discuss temporal and spatial aspects of Ca2+ signaling in beta-cells, the former involving the oscillatory activation of Ca2+ channels during glucose-induced electrical bursting, and the latter involving [Ca2+]i elevation in restricted microscopic "domains," as well as direct interactions between Ca2+ channels and secretory SNARE proteins. Finally, I review the evidence supporting a possible role for Ca2+ release from the endoplasmic reticulum in glucose-dependent insulin secretion, and evidence to support the existence of novel Ca2+ entry pathways. I also show that the beta cell has an elaborate and complex set of [Ca2+]i signaling mechanisms that are capable of generating diverse and extremely precise [Ca2+]i patterns. These signals, in turn, are exquisitely coupled in space and time to the beta-cell secretory machinery to produce the precise minute-to-minute control of insulin secretion necessary for body energy homeostasis. PMID- 11216637 TI - Regulation of adenohypophyseal pyroglutamyl aminopeptidase II activity by thyrotropin-releasing hormone and phorbol esters. AB - Thyrotropin-releasing hormone (TRH) is inactivated by a narrow specificity ectopeptidase, pyroglutamyl aminopeptidase II (PPII), in the proximity of target cells. In adenohypophysis, PPII is present on lactotrophs. Its activity is regulated by thyroid hormones and 17beta-estradiol. Studies with female rat adenohypophyseal cell cultures treated with 3,3',5'-triiodo-L-thyronine (T3) showed that hypothalamic/paracrine factors, including TRH, can also regulate PPII activity. Some of the transduction pathways involve protein kinase C (PKC) and cyclic adenosine monophosphate (cAMP). The purpose of this study was to determine whether T3 levels or gender of animals used to propagate the culture determine the effects of TRH or PKC. PPII activity was lower in cultures from male rats. In cultures from both sexes, T3 induced the activity. The percentages of decrease due to TRH or PKC were independent of T3 or gender; the percentage of decrease due to cAMP may also be independent of gender. These results suggest that T3 and hypothalamic/paracrine factors may independently control PPII activity in adenohypophysis, in either male or female animals. PMID- 11216638 TI - Diabetogenic role of insulin's counterregulatory hormones in the isletectomized, diabetic goby. AB - In an experimental model of insulin-dependent diabetes mellitus (IDDM) in the teleost fish, the goby Gillichthys mirabilis, an isletectomy procedure completely removes the pancreatic endocrine tissue without affecting the exocrine acini or other essential tissues. Interestingly, isletectomized (Ix) gobies do not exhibit a significant hyperglycemia until 10-15 d after this procedure, suggesting a lack of initial diabetogenic actions of a pancreatic factor(s). Administering exogenous glucagon in otherwise nonsymptomatic 7-d Ix gobies, however, induces a hyperglycemic state comparable to that in severely diabetic rats or gobies (after 20 d post-Ix). The spontaneously arising hyperglycemia observed between 10 and 15d post-Ix, on the other hand, is significantly correlated with increasing serum cortisol concentrations, with both exhibiting sustained elevated levels (approx 23 mmol/L and >100 ng/mL, respectively) at 20- and 25-d post-Ix. Exogenous cortisol treatment also significantly induced hyperglycemia in nonsymptomatic, 7 d Ix gobies. By contrast, growth hormone (GH) had no detectable diabetogenic effect in 7-d Ix gobies. Serum levels of ammonia, the principal nitrogenous waste in this species, were not affected by glucagon treatment but were reduced slightly by GH treatment (30% reduction; p < 0.05). Cortisol treatment, on the other hand, increased ammonia levels twofold, suggesting that the glucocorticoid induces a negative nitrogen balance. These results indicate that the counterregulatory hormones--glucagon and cortisol--are effective diabetogenic factors in the Ix goby, capable of driving metabolic imbalance in this model of IDDM. PMID- 11216639 TI - Effects of chronic dietary exposure to genistein, a phytoestrogen, during various stages of development on reproductive hormones and spermatogenesis in rats. AB - Developmental, hormonal, and gametogenic parameters were evaluated in male progeny following chronic dietary exposure to the phytoestrogen genistein. Twenty pregnant rats were fed a diet containing genistein (50 microg/d) from d 17 of gestation, and 12 were fed a control diet without genistein. Four litters each of control and genistein-fed rats were euthanized on d 21. The remaining pups were weaned on d 21 and only male rats were used in this study. On d 21, eight litters of genistein-fed rats were placed on control diet (gestational and lactational exposure alone [GL-G]), and the remaining eight continued on genistein diet (lifelong exposure group [LL-G]). These rats were euthanized (four litters/group) on d 70 or 130 of life. Serum testosterone, which was slightly reduced in genistein-exposed rats on d 21, did not differ among treatment and control groups on d 70 and 130. Serum luteinizing hormone of genistein-exposed rats was reduced on d 21 and 130, but not on d 70. Serum follicle-stimulating hormone did not vary among groups at any age. Treatment-related effects of dietary genistein were not observed on the weights of the testes of 21-d-old rats. Except for a slight decrease in testis weight of GL-G rats at 130 d, no significant effect of dietary exposure was observed on the weight of the testes in any other group. However, epididymal weights were significantly reduced in both treated groups at d 130. Testicular sperm count (on d 70 as well as 130) also was not affected in GL-G or LL-G rats. We conclude that gestational plus lactational exposure to genistein and subsequent dietary exposure to genistein have no adverse effects on gametogenic function in male rats. PMID- 11216640 TI - The N-terminal domain of the mineralocorticoid receptor modulates both mineralocorticoid receptor- and glucocorticoid receptor-mediated transactivation from Na/K ATPase beta1 target gene promoter. AB - Mineralocorticoid and glucocorticoid hormones activate the expression of the Na/K ATPase beta1 through direct binding of the mineralocorticoid receptor (MR) and glucocorticoid receptors (GR) to a mineralocorticoid- and glucocorticoid responsive element in the beta1 promoter region, but activation of the beta1 promoter is inhibited by coexpression of both receptors. Here, using a series of mutated and chimeric receptors, we show that the N-terminal region of MR mediates an inhibitory effect on MR and GR activation from the beta1 promoter, in CV-1 cells. Deletion of the N-terminal region of MR (1-603) enhanced MR activation four-fold. Activation by chimeric MR, in which the N-terminus of GR replaces the N-terminal region of MR, was threefold that of wild-type MR. In addition, whereas coexpression of wild-type MR and GR was inhibitory, coexpression of chimeric MR and wild-type GR was nearly equal to that of MR. By contrast, mutated GR lacking its N-terminal region (1-420) was less efficient than the wild type in activating this promoter. These results demonstrate that the N-terminal domains of MR and GR have opposite transactivation properties and that MR region 1-603 is indeed inhibitory for both MR- and GR-mediated regulation of the Na/K ATPase beta1 gene promoter. PMID- 11216641 TI - Autocrine role of gonadotropin-releasing hormone and its receptor in ovarian cancer cell growth. AB - We have recently proposed an autocrine role of gonadotropin-releasing hormone (GnRH) and its receptor (GnRH-R) in human ovarian surface epithelium. In the present study, we examine the presence and role of a GnRH/GnRH-R loop in epithelial ovarian cancer cells, OVCAR-3. A dose-dependent biphasic response in GnRH and GnRH-R mRNA levels were observed after treating with GnRH agonist [GnRHa, (D-Ala6)-GnRH], for 24 h. High concentrations of GnRHa (10(-9) M and 10( 7)) decreased the GnRH and GnRH-R mRNA levels, whereas a low concentration (10( 11) M) resulted in an upregulation of GnRH and GnRH-R genes expression. Cotretment with the competitive antagonist, antide, prevented the biphasic effect induced by GnRHa, confirming the specificity of the response. In addition, GnRHa treatment resulted in a time- and dose-dependent inhibition on OVCAR-3 cells growth. A significant inhibition of proliferation was detected as early as the d 2 of treatment. Treatment with 10(-7) M GnRHa induced DNA fragmentation in OVCAR 3 cells, suggesting that the GnRHa-induced antiproliferation in OVCAR-3 cells was mediated by apoptosis. Again, this effect was prevented by cotreatment of antide. Taken together, our findings strongly support the notion that GnRH acts as an autocrine/paracrine regulator of ovarian cancer cell proliferation. PMID- 11216642 TI - Parathyroid hormone and transforming growth factor-beta1 coregulate chondrocyte differentiation in vitro. AB - Parathyroid hormone (1-34) (PTH(1-34) and transforming growth factor-beta1 (TGF beta1) regulate chondrocyte proliferation, differentiation, and matrix synthesis. Both proteins mediate their effects in a dose- and time-dependent manner, and the effects are cell maturation specific. Moreover, similar signaling pathways are used, suggesting that there may be cross talk leading to coregulated cell response. To test this hypothesis, confluent cultures of rat costochondral resting zone and growth zone chondrocytes were treated with 0.22, 0.44, or 0.88 ng/mL of rhTGF-beta1 for 24 h, followed by treatment with 10(-11) to 10(-8) M PTH(1-34) for 10 min or 24 h. [3H]-Thymidine incorporation, specific activity of alkaline phosphatase (AP), and [35S]-sulfate incorporation were measured. PTH(1 34) had no effect on [3H]-thymidine incorporation by growth zone cells pretreated with 0.22 or 0.44 ng/mL of TGF-beta1, but in cultures treated with 0.88 ng/mL, PTH(1-34) caused a dose-dependent decrease that was maximal at the lowest concentration tested. By contrast, PTH(1-34) stimulated [3H]-thymidine incorporation by resting zone cells, and this effect was additive with the stimulation caused by 0.22 ng/mL of TGF-beta1. PTH(1-34) caused a synergistic increase in AP in growth zone cells treated with 0.44 or 0.88 ng/mL of TGF-beta1, but not in cells treated with 0.22 ng/mL of TGF-beta1. It had no effect on AP in resting zone cells pretreated with any concentration of TGF-beta1. PTH(1-34) increased [35S]-sulfate incorporation in growth zone and resting zone cell cultures treated with 0.22 ng/mL of TGF-beta1 to levels seen in cultures treated with 0.88 ng/mL of TGF-beta1 alone. These results support the hypothesis that PTH(1-34) and TGF-beta1 coregulate growth plate chondrocytes and that the effects are cell maturation dependent. PMID- 11216644 TI - Thyroid-associated ophthalmopathy in black South Africans with Graves' disease: relationship to serum antibodies reactive against eye muscle and orbital connective tissue autoantigens. AB - The prevalence of hyperthyroidism owing to Graves' disease is increasing among urban black South Africans. Thyroid-associated ophthalmopathy is often observed in this context, but its pathogenesis remains unclear. No close relationship has been noted between antiflavoprotein (Fp) antibodies or thyrotropin receptor antibodies and ocular involvement in black patients. We measured serum antibodies against eye muscle and orbital connective tissue antigens in black patients with Graves' disease, correlating them with eye signs. Of 11 patients with clinical ophthalmopathy, 2 (18%) had antibodies against collagen type XIII, 3 (27%) against flavine adenine dinucleotide (FAD), 1 (9%) against Fp, and 4 (35%) against G2s. Antibody prevalences in eight patients without clinical ophthalmopathy were 12.5% for collagen XIII, 12.5% for FAD, 25% for Fp and 0% for G2s. These differences were not statistically significant. None of the individual mean antibody levels were significantly different between the two subgroups of thyrotoxic patients. Serum antibody levels were negative in 10 black South African controls. In summary, eye muscle and orbital connective tissue antibodies were found in small proportions of patients with Graves' disease with no close relationship of any antibody to eye signs. Thus, a substantial proportion of black South Africans with overt clinical ophthalmopathy remains in whom currently availabe serologic tests are unhelpful for screening and laboratory confirmation. PMID- 11216643 TI - Neuroendocrine mechanisms for reproductive senescence in the female rat: gonadotropin-releasing hormone neurons. AB - Reproductive aging in female rats is characterized by profound alterations in the neuroendocrine axis. The preovulatory luteinizing hormone (LH) surge is attenuated, and preovulatory expression of the immediate early gene fos in gonadotropin-releasing hormone (GnRH) neurons is substantially reduced in middle aged compared with young rats. We tested the hypothesis that alterations in GnRH gene expression may be correlated with the attenuation of the LH surge and may be a possible mechanism involved in neuroendocrine senescent changes. Sprague-Dawley rats ages 4 to 5 mo (young), 12-14 mo (middle-aged), or 25 to 26 mo (old) were killed at 10:00 AM or 3:00 PM on proestrus, the day of the LH surge, or diestrus I in cycling rats, and on persistent estrus or persistent diestrus in acyclic rats. RNase protection assays of GnRH mRNA and GnRH primary transcript were performed. GnRH mRNA levels increased significantly with age, whereas GnRH primary transcript levels, an index of GnRH gene transcription, decreased in old compared to young and middle-aged rats. This latter result suggests that an age related change in GnRH mRNA levels occurs independently of a change in gene transcription, indicating a potential posttranscriptional mechanism. On proestrus, GnRH mRNA levels increased significantly from 10:00 AM to 3:00 PM in young rats. This was in contrast to proestrous middle-aged rats, in which this afternoon increase in GnRH mRNA levels was not observed. Thus, the normal afternoon increase in GnRH mRNA levels on proestrus is disrupted by middle age and may represent a substrate for the attenuation of the preovulatory GnRH/LH surge that occurs in rats of this age, prior to reproductive failure. PMID- 11216646 TI - Low frequency of rearrangement of TRK protooncogene in Chinese thyroid tumors. AB - The TRK protooncogene (NTRK1) encodes a cell-surface transmembrane tyrosine kinase (TK) acting as a receptor for nerve growth factor. Oncogenic potential in thyrocytes results from replacing the 5' portion by regulatory parts of other genes, leading to constitutive TK expression. In Italy, human papillary thyroid carcinoma (PTC) shows a frequent activation (50%) of the TK receptor genes NTRK1 and RET. Both genes undergo oncogenic rearrangements by the same mechanism. We previously reported high frequency (6/11) of rearrangement of the RET protooncogene in Chinese PTCs. Wide differences in the frequency (0-10.9%) of the NTRK1 rearrangement in PTCs have been reported in different populations. To investigate the frequency of TRK protooncogene rearrangement in Chinese thyroid tumors, we performed reverse transcriptase polymerase chain reaction to amplify specific TRK rearrangement transcripts. We examined thyroid tumors of 40 patients, including 14 papillary carcinomas, 4 follicular carcinomas, 1 Hurthle cell carcinoma, 1 insular carcinoma, and 20 nodular goiters. NF874 NIH3T3, NF723 NIH3T3, NF861 NIH3T3, and NF881 NIH3T3 were used as controls for TRK-T3, TRK-T2, TRK-T1, and TRK, respectively. No known TRK protooncogene rearrangements were detected among the 40 thyroid tumors in our studies. We suggest that the TK receptor NTRK1 activation seems less important than RET activation in PTCs in the Chinese population. PMID- 11216645 TI - Stimulus-secretion coupling of arginine-induced insulin release: comparison between the cationic amino acid and its methyl ester. AB - The role currently ascribed to the accumulation of L-arginine in the pancreatic islet B-cell as a determinant of its insulinotropic action was reevaluated by comparing the uptake and the metabolic, ionic, electric, and secretory effects of the cationic amino acid with those of its more positively charged methyl ester in rat pancreatic islets. The response to L-arginine methyl ester differed from that evoked by the unesterified amino acid by a lower uptake and oxidation, lack of inhibitory action on D-glucose metabolism, more severe inhibition of the catabolism of endogenous L-glutamine, inhibition of 45Ca net uptake, decrease in both 86Rb outflow from prelabeled islets perifused at normal extracellular Ca2+ concentration and 45Ca efflux from prelabeled islets perifused in the absence of extracellular Ca2+, and delayed and lesser insulinotropic action. These findings reinforce the view that the carrier-mediated entry of L-arginine into the islet B cells, with resulting depolarization of the plasma membrane, represents the essential mechanism for stimulation of insulin release by this cationic amino acid. PMID- 11216648 TI - Evidence for biosynthesis of preproinsulin in gut of rat. AB - Glucagon and other pancreatic peptides are made in the gut, but there is little evidence for the formation of insulin. The demonstration of insulin receptors on the mucosa of gut epithelium suggests that there may be an autocrine or paracrine role for insulin made in the gut. Such insulin may control cell division, the secretion of other peptides from the same or neighboring cells, or motility and absorption. To search for the ability of the gut to make insulin, sections of freshly excised segments of rat gut were treated with an antiserum against porcine insulin. Intracellular immunoreactivity appeared in glandular cells in the stomach and colon but not in the small intestine. Preproinsulin mRNA was detected in similar cells in the stomach and colon by in situ hybridization, using specific oligonucleotide probes. Rat preproinsulin 1 and 2 mRNAs were transcribed by reverse transcriptase to the corresponding cDNAs, which were then amplified by polymerase chain reaction, utilizing specific oligonucleotide primers. Restriction analysis confirmed the identity of rat preproinsulin 1 and 2 mRNA in the colon and rat preproinsulin 1 mRNA in the stomach. Neither was found in the small intestine. Base sequences of the cDNAs were identical to the coding regions of pancreatic rat preproinsulin 1 and 2 messages. These observations are strong evidence for the synthesis of preproinsulin in the gut of the rat. PMID- 11216647 TI - Real-time detection of insulin-like growth factor-1 stimulation of the MAC-T bovine mammary epithelial cell line. AB - Binding of growth factors by cell-surface receptors is an essential means by which cells regulate normal tissue growth and differentiation. Exposure to growth factors is often transient, and our goal was to determine whether short-term exposure to insulin-like growth factor-1 (IGF-1) would lead to activation, assayed as cell proliferation, of mammary epithelial cells. The MAC-T cell line is an immortalized bovine mammary epithelial cell line, chosen as our model mammary cell line because of its known sensitivity to IGF-1. Using the Cytosensor Microphysiometer System, a biosensor capable of measuring extracellular acidification, we were able to measure activation of the cells owing to IGF-1 addition in real time and found that peak acidification occurred in only 14 min. We show that this rapid response to IGF-1 is dose dependent and specific for IGF 1. A significant increase in [3H]thymidine incorporation by cells after a similar short-term exposure to IGF-1 suggests that the measured increase in extracellular acidification following IGF-1 addition is physiologically relevant. This technology offers a new, novel, and rapid means for the study of IGF-1 activity, as well as the screening of IGF-1 inhibitors, in mammary epithelial cells. PMID- 11216649 TI - A follicle-stimulating hormone receptor ecto-domain epitope that is a target for receptor immunoneutralization yet does not affect ligand contact and activation. AB - The follicle-stimulating hormone receptor (FSHR) large extracellular domain suggests that interaction of ligand with receptor is likely to be complex. Residues 265-296 of the FSHR are part of a sequence primarily nonhomologous with other glycoprotein hormone receptors. A reasonable hypothesis is that this sequence of the FSHR plays a role in binding FSH. Flow cytometry studies of this region revealed that antibody X179 against peptide R265-S296 binds to human FSHR expressed by CHO cells and can be competed against by preincubating the cells with hFSH. These results suggested that the region corresponding to residues 265 296 in the extracellular domain of the FSHR is involved in binding to hormone. To test this hypothesis 10 scanning alanine mutants of rFSHR at the 265-296 epitope were generated, and the binding characteristics of these mutants were studied. Their affinity constants for 125I-hFSH did not deviate greatly from that of wild type FSHR, in which some mutants exhibited an approximately two- to threefold reduction in Ka compared to wild-type receptor, and no mutation abolished signal transduction. These results lead to rejection of the hypothesis that this region contains residues critical for conveying hormone specificity and receptor dependent hormone action. PMID- 11216651 TI - Progesterone together with estrogen attenuates homologous upregulation of gonadotropin-releasing hormone receptor mRNA in primary cultured rat pituitary cells. AB - In a previous study, we clearly demonstrated that an application of gonadotropin releasing hormone (GnRH) to cultured rat pituitary cells increased the expression of GnRH receptor (GnRH-R) mRNA through transcriptional activation of GnRH-R gene rather than suppression of the turnover rate of GnRH-R mRNA. Along with GnRH, gonadal steroids seem to be an important regulator for GnRH-R expression in the pituitary gland. Recent in vivo studies reported that an application of gonadal steroids to gonadectomized animals modulated GnRH-R mRNA expression in the pituitary gland. However, it has not been clearly understood whether steroids may act directly at the pituitary or indirectly via modulation of hypothalamic GnRH release. Therefore, we assessed the effects of estrogen and progesterone on GnRH R mRNA expression in primary cultured female rat pituitary cells. Neither estradiol nor progesterone modulates the basal expression of GnRH-R mRNA in primary cultured pituitary cells. When cultured pituitary cells were exposed to different doses of estradiol in combination with GnRH (0.2 nM), the GnRH stimulated increment of GnRH-R mRNA expression was not significantly changed by estradiol at any given doses. However, when different doses of progesterone were added to primary cultured pituitary cells in combination with GnRH (0.2 nM), GnRH induced increases in GnRH-R mRNA levels were reduced in a dose-related manner, showing a significant reduction at 100 nM progesterone. Furthermore, the addition of estradiol reinforced the suppressive effect of progesterone on the homologous upregulation of GnRH-R mRNA expression. Collectively, our results clearly demonstrated that progesterone directly attenuates the homologous upregulation of GnRH-R mRNA expression at the pituitary level, and that estradiol potentiates the effect of progesterone. PMID- 11216650 TI - Stimulation by interleukin-6 and inhibition by tumor necrosis factor of cortisol release from bovine adrenal zona fasciculata cells through their receptors. AB - Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are synthesized and released from adrenal cells. Therefore, the effects of TNF-alpha and IL-6 on cortisol release from bovine zona fasciculata (ZF) cells were investigated. IL-6 (10-1000 pg/mL) significantly increased basal and adrenocorticotropic hormone (ACTH)-stimulated cortisol release in a concentration-dependent manner. This stimulatory effect of IL-6 became apparent at intervals as short as 4 h and continued through 24 h. IL-6 also potentiated the cortisol release stimulated by the adenylyl cyclase activator forskolin. By contrast, TNF-alpha (0.1-10 ng) inhibited basal and ACTH-stimulated cortisol release in a concentration-dependent manner. The inhibitory effects of TNF-alpha on cortisol release were significant at time intervals as short as 4 h and continued through 24 h. TNF-alpha inhibited forskolin-stimulated cortisol release. Binding studies demonstrated that ZF cells have IL-6 receptors (100 receptors/cell, Kd of 7.5 x 10(-11)) and TNF receptors (200 receptors/cell, Kd of 2.4 x 10(-9) M). Immunohistochemical analysis provided evidence that the majority of ZF cells have IL-6 receptors, TNF type 1 receptors, and TNF type 2 receptors. Because IL-6 and TNF-alpha are released from the adrenal cortex and these cytokines modify the release of cortisol from the ZF, IL 6 and TNF-alpha may play a paracrine or autocrine role in the regulation of adrenal function. PMID- 11216652 TI - Involvement of phosphoinositide-3-kinase and p70 S6 kinase in regulation of proliferation of rat lactotrophs in culture. AB - Phosphoinositide-3-kinase (PI-3K) and p70 S6 kinase (p70S6k) are suggested as important molecules for mediating mitogenic actions of growth factors and cytokines in a variety of cell types. The purpose of the present study was to investigate whether these kinases were involved in mediation of the mitogenic actions of not only the growth factor insulin but also cyclic adenosine monophosphate (cAMP) and estrogen on rat cultured lactotrophs. Treatment with wortmannin or LY294002, a PI-3K inhibitor, or rapamycin, a p70S6k inhibitor, decreased basal levels of 5-bromo-2-deoxyuridine (BrdU)-labeling indices of lactotrophs in a dose-dependent manner. These inhibitors were effective in blocking an increase in BrdU-labeling indices induced by insulin. LY294002 and rapamycin also suppressed an increase in BrdU-labeling indices induced by forskolin, an adenylate cyclase activator, or dibutyryl cAMP, a membrane permeable cAMP analog, as well as that induced by estradiol, a physiologic extracellular activator of lactotroph proliferation. However, the dibutyryl cAMP , but not insulin-induced proliferation, acquired a resistance to LY294002 and rapamycin by pretreatment with bromocriptine, a dopaminergic agonist that is able to suppress lactotroph proliferation. These results suggest that the mitogenic actions of cAMP and estradiol on rat lactotrophs are mediated by PI-3K and p70S6k, and that dopaminergic inhibition modifies the PI-3K and p70S6k dependence of the regulation of lactotroph proliferation. PMID- 11216653 TI - Effect of angiotensin II on rat renal cortical 11beta-hydroxysteroid dehydrogenase. AB - Renal 11beta-hydroxysteroid dehydrogenases (11beta-HSDs) are subject to modulation by various endogenous factors. 11beta-HSDs convert glucocorticoids into inactive 11-ketones and thereby determine tissue levels of active glucocorticoids and thus the extent of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) activation. As such, modulation of the activity of renal 11beta-HSDs may contribute to the cascade of regulatory events involved in renal electrolyte water handling. We investigated whether renal 11beta-HSDs are modulated by elevated circulating angiotensin II. In rats infused for 2 wk with angiotensin II (250 ng/[kg x min] subcutaneously), plasma angiotensin II, aldosterone, and corticosterone were raised 5.1-, 10.7-, and 2.3-fold, respectively, compared with control rats. Angiotensin II infusion raised corticosterone 11beta-oxidation 1.46- and 1.35-fold in renal cortical proximal and distal tubules (enriched by Percoll centrifugation), respectively, but had no effect on 11beta-HSD1 and 11beta-HSD2 mRNA levels (semiquantitative reverse transcriptase polymerase chain reaction), except for distal tubular 11beta-HSD1 mRNA, which was decreased to 50%. In vitro treatment of freshly isolated tubules with angiotensin II for 45 min prior to assessment of 11beta-HSD activity showed no direct acute effects of angiotensin II on tubular corticosterone 11beta oxidation. The enhanced renal tubular corticosterone 11beta-oxidation in vivo may partly protect renal GR and MR from elevated plasma corticosterone on angiotensin II infusion. PMID- 11216654 TI - Combined modification of intracellular and extracellular loci on human gonadotropin-releasing hormone receptor provides a mechanism for enhanced expression. AB - The mammalian gonadotropin-releasing hormone (GnRH) receptor (GnRH-R) has been a therapeutic target for human and animal medicine. This receptor is a unique G protein-coupled receptor that lacks the intracellular C-terminal domain commonly associated with this family. Development of highthrough put screens for agents active in humans has been hampered by low expression levels of the hGnRH-R in cellular models. Two sites have attracted the interest of laboratories studying regulation of expression. The chimeric addition of the C-terminal tail from catfish GnRH-R (cfGnRH-R) to the rat GnRH-R significantly augmented receptor expression in GH3 cells. In addition, rodent GnRH-R contains 327 amino acids, but cow, sheep, and human GnRH-R (hGnRH-R) contain 328 residues, the "additional" residue being a Lys 191. Deletion of Lys 191 (del 191) from the hGnRH-R resulted in increased receptor expression levels and decreased internalization rates in both COS-7 and HEK 293 cells. In this study, the combined effect of the addition of the C-tail from cfGnRH-R and deletion of the Lys 191 from the hGnRH-R was compared to expression of the wild-type (WT) or either alteration alone in a transient expression system using primate cells. The altered receptor (hGnRH R[del 191]-C-tail) showed significantly increased receptor expression at the cell surface compared with the WT or either modification alone. The inositol phosphate response to stimulation was also significantly elevated in response to GnRH agonist. After treatment with a GnRH agonist, the altered receptors showed a slower internalization rate. The homologous steady-state regulation of the WT and the altered receptors was similar, although the response of the altered receptors was significantly decreased. These results suggest that the conformational change in the receptor as a result of the deletion of Lys 191 and the addition of the C terminus tail substantially increased the steady-state receptor expression and decreased internalization and homologous regulation. Because the effects on expression are greater than additive, it appears that these alterations exert their effects by differing means. These techniques for expression of the hGnRH-R in transfected mammalian cells provide the basis for a therapeutic screen for GnRH analogs, agonists, and antagonists of the hGnRH. PMID- 11216655 TI - Pancreatic fate of 6-deoxy-6-[125I]iodo-D-glucose: in vitro experiments. AB - The apparent distribution space of 6-deoxy-6-[125I]iodo-D-glucose, recently proposed as a tracer of D-glucose transport, was measured in rat isolated islets, acinar tissue, and pieces of pancreas. While such a space reached a steady-state value corresponding to the 3HOH volume in pancreatic islets within 5 min, it slowly increased in pieces of pancreas and, even after 60-min incubation, remained lower than the 3HOH volume. Moreover, the net uptake of 6-deoxy-6 [125I]iodo-D-glucose by pancreatic pieces was inhibited by unlabeled 6-deoxy-6 iodo-D-glucose, D-glucose, and cytochalasin B, while being less or not affected by these agents in isolated islets. A preferential labeling of the endocrine, relative to exocrine, moiety of the pancreas was documented both by comparing, after 2 min incubation, the uptake of 6-deoxy-6-[125I]iodo-D-glucose by pieces of pancreas from normal vs streptozotocin-injected rats and by comparing the radioactive content of pancreatic islets and acinar tissue obtained from normal rats injected intravenously 3 min before sacrifice with 6-deoxy-6-[125I]iodo-D glucose. It is proposed, therefore, that advantage could conceivably be taken from the vastly different time course for the uptake of selected monosaccharides by pancreatic islets vs acinar cells in the perspective of imaging of the endocrine pancreas by a non invasive method. PMID- 11216656 TI - The M34T allele variant of connexin 26. AB - GJB2 encodes the protein Connexin 26, one of the building blocks of gap junctions. Each Connexin 26 molecule can oligomerize with five other connexins to form a connexon; two connexons, in turn, can form a gap junction. Because mutations in GJB2 are the most common cause of congenital severe-to-profound autosomal recessive nonsyndromic hearing loss, the effect of the Connexin 26 allele variants on this dynamic 'construction' process and the function of any gap junctions that do form is particularly germane. One of the more controversial allele variants, M34T, has been hypothesized to cause autosomal dominant nonsyndromic hearing loss. In this paper, we present clinical and genotypic data that refutes this hypothesis and suggests that the effect of the M34T allele variant may be dependent on the mutations segregating in the opposing allele. PMID- 11216657 TI - Connexin-26 gene analysis in hearing-impaired newborns. AB - The efficacy and utility of the Connexin-26 (Cx-26) gene (also called GJB2) analysis from DNA isolated from Guthrie newborn screening cards is demonstrated. This analysis precisely defined a major cause of prelingual nonsyndromic deafness in those children requiring amplification in our study. Guthrie cards were obtained from 49 deaf children requiring amplification identified over the last 5 years by the Rhode Island Newborn Screening Program. Children with syndromes or other recognizable causes of hearing loss were excluded. DNA was extracted from the Guthrie cards and analyzed sequentially for the Cx-26 35delG mutation and then for the 167delT mutation followed by gene sequencing on remaining heterozygotes. Three of 42 children were 35delG homozygotes; 2/42 children were 35delG/167delT compound heterozygotes. One child was identified as being a 35delG heterozygote with no other mutation found by sequencing. Nine Guthrie cards yielded no amplification or uninterpretable results. Cx-26 mutations were identified as causing 11.9% of the deafness in the children studied. In conclusion, Cx-26 analysis is an important test that identifies a major cause of prelingual nonsyndromic deafness. Molecular analysis of hearing-impaired newborns will be important for genetic counseling in these families. Failures with Guthrie cards may make use of other collection methods preferable. PMID- 11216658 TI - Biallelic discrimination assays for the three common Ashkenazi Jewish mutations and a common non-Jewish mutation, in Tay-Sachs disease, using fluorogenic TaqMan probes. AB - We have developed rapid semiautomated fluorogenic TaqMan assays for the three common Jewish mutations that occur in Tay-Sachs disease, the TATC 4-bp insertion in exon 11 (1,278insTATC), the IVS 12 + 1G --> C, splice site mutation in intron 12 (1421 + 1 G --> C), and the G --> A change at the 3' end of exon 7 (G269S), as well as for a non-Jewish mutation, IVS9 + I G --> A, believed to be prevalent in patients of Celtic descent. The TaqMan assays are designed to run on the ABI SDS 7700 sequence detection system, using allele-specific probes that carry a reporter dye at the 5' end and a quencher dye at the 3' end. Using a 96-well format, all four assays can be performed simultaneously on the same plate, with real-time fluorescence detection or just an end-point plate read. DNA samples from 78 patients identified as carriers by biochemical screening and genotyped by conventional techniques were used to assess the accuracy and efficiency of the probes in allelic discrimination assays. There were no discrepancies noted between previously assigned genotypes and the results obtained by application of this methodology. PMID- 11216659 TI - Disclosure of Huntington's disease to family members: the dilemma of known but unknowing parties. AB - Predictive genetic testing presents unique issues in the legal and ethical debate concerning disclosure of information within the physician-patient relationship. A duty to disclose information to family members has been found when the disclosure is likely to result in the ability to mitigate the damaging effects of the disease. When evaluating the situation where a individual is at risk of Huntington's disease, the analysis must be different, as shown in this paper, and necessitates an ethical and legal examination of the consequences of receipt of the information on family members, those known but unknowing parties who are at risk of inheriting a genetic disease. This paper analyzes the potential legal duty of a physician to disclose or withhold genetic information from the family members of patients. Existing statutes governing genetic information do not directly address the interests of family members. Courts that have ruled on the duty to disclose medical or genetic information have analyzed these issues using traditional concepts of tort law. Yet the situation presented by Huntington's disease is unique and demands a different framework for analysis, given the late onset and lack of curative or ameliorative treatment. This paper also analyzes the ethical standards to be invoked when considering violating the privacy of a patient or a family member. The principles of autonomy and self-determination of family members are considered, versus the risk of harm and the privacy interest in not knowing potentially devastating information. PMID- 11216660 TI - Novel mutations in the duplicated region of the polycystic kidney disease 1 (PKD1) gene provides supporting evidence for gene conversion. AB - Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common human single-gene disorders, and is the most common inherited form of cystic kidney disease. It is estimated that approximately 85% of ADPKD is due to mutations in the PKD1 gene, which is located on chromosome 16p13.3. Mutation analysis in this gene is difficult, because more than two-thirds of reiterated several times at 16p13.1. In this study, mutation screening in 90 ADPKD patients was carried out on exons in the duplicated region of the PKD1 gene (23-34), using genomic long-range PCR followed by nested PCR and single-strand conformation polymorphism (SSCP), and finally cycle sequencing. Two nonconservative missense mutations were detected in exons 25 and 31, and two conservative mutations were found in exons 24 and 29. A novel splicing mutation, which is expected to cause skipping of exon 30, was detected in one case. Moreover, six intronic variants, three silent variants, and one polymorphic variant were detected in this study. Comparison between some of these changes and published sequences from the homologous genes on 16p13.1, revealed supporting evidence for the gene conversion theory as a mechanism responsible for some of the mutations in the PKD1 gene. Factors likely to facilitate gene conversion in this region of the PKD1 gene are discussed. PMID- 11216661 TI - Detection of an unusual combination of mutations in the HFE gene for hemochromatosis. AB - In the present paper, we describe an individual, found as part of a screening study, being homozygous for the C282Y mutation and at the same time heterozygous for the H63D mutation in the HFE gene. Identical results were obtained by three different methods, i.e., by PCR-RFLP, by sequencing, and by melting curve analysis. Thus, the common conception that the C282Y and the H63D mutations are mutually exclusive is not valid. Clinical symptoms and laboratory data on the individual were similar to hemochromatosis patients homozygous for the C282Y mutation. The implications of our finding for diagnostic analytical laboratory procedures are briefly discussed. PMID- 11216662 TI - Prenatal genotyping for the RhD blood group antigen: considerations in developing an accurate test. AB - Experience performing prenatal genotyping for RHD has shown that consideration must be given to developing a molecular test capable of detecting recombination/gene conversion events involving the RHD and RHCE genes that can lead to erroneous results. Out of 50 prenatal RHD tests performed over the past 5 years, four samples were encountered that gave false-positive results. In only one of the tests, incorrect results were issued to the physician. In the other three instances, the erroneous nature of the test results was revealed through the analysis of multiple regions of the RHD gene and, more importantly, because the mother, and sometimes the father, were tested in parallel with the fetus. In an extension of the observations obtained from the prenatal testing program, a large panel of RhD-negative blood donors were subjected to molecular analysis of the RHD gene. Of 1,183 donors screened, 187 were found to phenotype as RhD negative. Of the 187 donors confirmed RhD negative serologically, 22 (11.8%) were found to retain remnants of the RHD gene that, depending upon the characteristics of the molecular assay performed, could lead to a false-positive result in a genotyping assay. On the basis of the experience presented here, it is recommended that any molecular RHD assay include an analysis of multiple areas of the RHD gene so as to allow for the detection of recombination/gene conversion events between the RHD and RHCE genes. Moreover, it is strongly recommended that the mother (at a minimum) and father be subjected to molecular analysis simultaneously with the fetus to confirm that the known phenotypes of the parent(s) are consistent with their respective genotypes. PMID- 11216663 TI - Does the A3333G mutation in the CACNL1A3 gene, detected in malignant hyperthermia, also occur in central core disease? AB - Malignant hyperthermia (MH) and central core disease (CCD) are two conditions associated with susceptibility to volatile anesthetics and depolarizing muscle relaxants. The gene RYR1, encoding the Ca2+ release channel of skeletal muscle sarcoplasmic reticulum, is responsible for about 50% of the cases of MH and some cases of CCD. However, genetic heterogeneity occurs in MH and a mutation in a second gene (CACLN1A3), encoding the alpha1-subunit of the dihydropyridine (DHP) channel, has recently been found in a large MH French family. The presence of this mutation in patients with CCD has not yet been reported. In this study, we analyzed the A3333G mutation in 5 unrelated patients affected by CCD and 31 MH susceptible relatives (from 19 MH families) and did not find this mutation in any of them. Nevertheless, the report of data on newly described mutations in different populations is important to estimate the contributions of each gene mutation to the phenotype of MH and CCD. PMID- 11216664 TI - Prader-Willi syndrome: genetic tests and clinical findings. AB - Here we describe the genetic studies performed in 53 patients with the suspected diagnosis of Prader-Willi syndrome (PWS). PWS is characterized by neonatal hypotonia, hypogonadism, delayed psychomotor development, hyperphagia, obesity, short stature, small hands and feet, learning disabilities, and obsessive compulsive behavior. Through the methylation analysis of the SNRPN gene, microsatellite studies of loci mapped within and outside the PWS/AS region, and fluorescence in situ hybridization (FISH) study, we confirmed the diagnosis in 35 patients: 27 with a paternal deletion, and 8 with maternal uniparental disomy (UPD). The clinical comparisons between deleted and UPD patients indicated that there were no major phenotype differences, except for a lower birth length observed in the UPD children. Our sample was composed of more girls than boys; UPD patients were diagnosed earlier than the deleted cohort (2(10/12) s. 7(9/12) years); and, in the deleted group, the boys were diagnosed earlier than the girls (5(2/12) vs. 7(8/12) years, respectively). PMID- 11216665 TI - Characterization of a novel D1S80 pseudoallele. AB - During a D1S80 population study conducted for databasing purposes in the New York City Ashkenazi Jewish population, eight out of 96 samples were typed with a band corresponding to the position of a #15 allele. In seven of the eight samples, three bands appeared. Further investigation was needed to explain the high frequency of an allele considered so rare that it is not included in the commercially provided allelic ladder. After extraction of the putative D1S80 15 repeat amplicon band from the 6% polyacrylamide genotyping gel, the amplicon bands were reamplified with D1S80 primers. After retyping as putative 15 alleles, these samples underwent Southern hybridization with a D1S80 locus-specific probe followed by DNA sequence analysis. Sequence analysis revealed that these bands did not arise from true D1S80 15 alleles. However, the PCR product was of a size that fell within the allelic ladder region corresponding to the 15 band and contained end sequences with strong homology to the D1S80 primers. An alignment search of the sequenced product revealed that a portion of the amplicons contained 72% identity to a known gene. These results emphasize the importance of sequencing analysis when questions arise about the authenticity of an allele. PMID- 11216666 TI - Delineation of the spectrum of Wilson disease mutations in the Greek population and the identification of six novel mutations. AB - In this study, we report the further results of an ongoing project on the delineation of the spectrum of mutations on the ATP7B gene in Wilson disease (WD) patients of Greek origin. We have analyzed 24 additional families and detected 16 mutations (five frameshifts, two splice site, two nonsense, and seven missense), of which six are novel. On adding these results to the ones already published by us, we conclude that WD shows a marked allelic heterogeneity in the Greek population. Of the total number of mutations so far detected, the most common eight account for the molecular defect in 72.8% of the WD chromosomes. The most frequent mutation is the His0169Gln, which has a frequency of 28.5%, similar to those reported in North European populations. Using these data, an efficient strategy of mutation screening for WD is possible in this population, thus improving the possibility of preclinical diagnosis. PMID- 11216667 TI - The founder mutations in the BRCA1, BRCA2, and ATM genes in Moroccan Jewish women with breast cancer. AB - To gain insight into the molecular mechanisms underlying the inherited predisposition to breast cancer in non-Ashkenazi Jews, we genotyped 54 Jewish Moroccan women with breast cancer, unselected for family history of cancer, for the predominant Jewish mutations in BRCA1, BRCA2, and ATM. One patient (2%) was found to have the 185de1AG BRCA1 mutation, none was a carrier of the 6174delT BRCA2 mutation, and 2/54 (4%) were heterozygous for the ATM mutation. These rates were not significantly different from the rates in the general non-Ashkenazi population. These preliminary data may indicate that the predominant Jewish mutations in BRCA1, BRCA2, and ATM genes contribute little, if any, to breast cancer predisposition and risk among Moroccan Jews. PMID- 11216668 TI - Disease genes and chromosomes: disease maps of the human genome. PMID- 11216669 TI - Structure-activity studies of novobiocin analogs as modulators of the cytotoxicity of etoposide (VP-16). AB - We have previously reported that the antibiotic novobiocin enhanced the toxicity of the anticancer agent etoposide (VP-16) to several drug-sensitive and resistant tumor cell lines. The increase in VP-16 cytotoxicity produced by novobiocin was not due to the combined effects of these agents on topoisomerase II, but to inhibition by novobiocin of VP-16 efflux, which in turn led to increased accumulation of VP-16 and increased formation of potentially lethal VP 16-stabilized topoisomerase II-DNA covalent complexes. We have now identified novobiocin analogs that are essentially equivalent to novobiocin as inhibitors of the activity of topoisomerase II, but that are more potent than novobiocin (a) as modulators of the cytotoxicity of VP-16 to WEHI-3B leukemia and A549 lung carcinoma cells and (b) in increasing VP-16 accumulation in these cell lines. Thus, removal of the sugar moiety of novobiocin to form novobiocic acid enhanced the potency of the antibiotic as a modulator of VP-16, whereas the substituted coumarin ring alone (U-7587) was devoid of VP-16 modulatory activity. Modifications of the side chain of novobiocin significantly influenced modulatory activity, with cyclonovobiocic acid, which was formed from novobiocic acid by acid-catalyzed cycloaddition, being the most active in enhancing the cytotoxicity of VP-16. The increased potency of novobiocic acid and cyclonovobiocic acid as modulators of VP-16 activity was achieved with no change from novobiocin in the capacity of these analogs to inhibit the catalytic activity of mammalian topoisomerase II, indicating a change in the specificity of these analogs. PMID- 11216670 TI - Induction of hepatocellular carcinoma with high metastatic potential in WS/Shi rats: discovery of an inbred strain highly susceptible to the liver carcinogen N nitrosomorpholine. AB - We investigated the susceptibility of three inbred strains of rats to the hepatocarcinogen, N-nitrosomorpholine (NNM), to establish a spontaneous metastatic model of hepatocellular carcinoma (HCC). WS/Shi. SD/gShi, and F344/DuCrj rats were given 0.02% NNM in drinking water for 8 weeks and thereafter left without any treatment. The experiment ceased at week 20, because mortality markedly increased after this time point in WS/Shi rats. Liver weight was highest in WS/Shi rats among the three strains examined. The incidence of HCC was 15/15 (100%) in WS/Shi rats, 1/16 (6%) in SD/gShi rats, and 13/16 (81%) in F344/DuCrj rats surviving after NNM treatment. Metastasis to the lung was observed in HCC bearing rats at an incidence of 13/15 (87%) in WS/Shi, 1/1 in SD/gShi, and 6/13 (46%) in F344/DuCrj. Four-week administration of NNM resulted in a significantly higher BrdU-labeling index of hepatocytes in WS/Shi rats than in the other strains. These findings indicated that WS/Shi is the most sensitive strain to NNM and may be the most suitable strain for use as a spontaneous metastatic model of HCC among the strains of rats examined in the present study. PMID- 11216671 TI - Tumor amplified protein expression therapy: Salmonella as a tumor-selective protein delivery vector. AB - Attenuated strains of Salmonella typhimurium, VNP20009 and YS7212, when injected systemically to tumor-bearing mice, accumulated preferentially in tumors at levels at least 200-fold and, more commonly, 1000-fold greater than in other normal tissues. This selectivity occurred in subcutaneously implanted murine tumors, including B16F10 melanoma, M27 lung carcinoma, and colon 38 carcinoma. The preferential accumulation was also manifested in animals bearing human tumor xenografts, including Lox, C8186, DLD1, SW620, HCT116, HTB177, DU145, MDA-MB-231, and Caki. Four to five days after a single IV injection of 1 x 10(6) colony forming unit (cfu)/mouse, we routinely detected VNP20009 proliferation and accumulation at levels ranging from 1 x 10(8) to 2 x 10(9) cfu/g tumor. The amount of VNP20009 accumulated in the liver ranged from 3 x 10(4) to 2 x 10(6) cfu/g. The distribution of Salmonella in tumors was homogenous; YS7212 could be detected from the periphery to the interior portion of the tumors. Using mice with various immunodeficiencies, we also discovered the same preferential accumulation of Salmonella in tumors implanted in these mice. The use of Salmonella as a protein delivery vector was shown by IV administration of the bacteria expressing either green fluorescent protein (GFP) or cytosine deaminase (CD) into tumor-bearing mice. GFP and CD were detected in tumors, but not in livers, taken from mice inoculated with Salmonella carrying these genes. Bacteria accumulation and CD expression persisted in the tumors for up to 14 days after a single bolus IV administration of bacteria to tumor-bearing mice. PMID- 11216672 TI - Schedule-dependent interaction between raltitrexed and 5-fluorouracil in human colon cancer cell lines in vitro. AB - Raltitrexed (Tomudex) is a novel thymidylate synthase inhibitor with significant activity against advanced colorectal cancer. We studied the cytotoxic interactions of raltitrexed and 5-fluorouracil (5-FU) in four human colon cancer cell lines on various schedules. The cell growth inhibition after 5 days was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cytotoxic interactions at the IC80 level were evaluated by the isobologram method. Simultaneous exposure to raltitrexed and 5-FU for 5 days produced additive to synergistic effects in Colo201 cells, and produced additive effects in Colo321, LoVo, and WiDr cells. Simultaneous exposure to raltitrexed and 5-FU for 24 h produced additive effects in Colo201, LoVo, and WiDr cells, and produced antagonistic effects in Colo320 cells. Sequential exposure to raltitrexed for 24 h followed by 5-FU for 24 h produced additive effects in Colo201, Colo320, and LoVo cells, and produced antagonistic effects in WiDr cells. The reverse sequence produced additive effects in Colo201 cells, and produced antagonistic effects in Colo320, LoVo, and WiDr cells. Simultaneous exposure to raltitrexed and 5-FU for 4 h and sequential exposure to raltitrexed for 4 h followed by 5-FU for 4 h with a 20-h interval produced additive effects, while the reverse sequence produced antagonistic effects in LoVo and WiDr cells. These findings suggest that the simultaneous administration of raltitrexed and 5 FU or the sequential administration of raltitrexed followed by 5-FU may be the optimal sequence, while the reverse sequence may be inappropriate. Preclinical and clinical studies of the simultaneous administration of raltitrexed and 5-FU and the sequential administration of raltitrexed followed by 5-FU are required to better understand the antitumor, toxic, and pharmacokinetic interactions of this combination in order to develop the combination chemotherapy of raltitrexed and 5 FU. PMID- 11216673 TI - Radiation-induced cell cycle delays and p53 status of early passage melanoma cell lines. AB - Cell cultures exposed to DNA-damaging agents such as gamma radiation respond by arresting at cell cycle checkpoints, and the p53 tumor suppressor protein is strongly implicated in this behavior. We have investigated the TP53 status and cell cycle response to ionizing radiation of a series of early passage cell lines (designated NZM1 to NZM15) previously developed from patients with metastatic melanoma. The TP53 status of each of the cell lines was determined by single strand conformation polymorphism and DNA sequence analysis. The majority of the lines appeared to have a wild-type TP53 gene sequence, consistent with published studies. Two lines (NZM4 and NZM7.2) were found to have an identical T-->C transition mutation in nucleotide 721 (exon 7) of the coding region. NZM7.2 (mutant) and NZM7.4 (wild-type) were clonally derived from the same line (NZM7). The existence of radiation-induced cell cycle arrest in G and/or G2M phase was determined 16 h after irradiation (6.3 Gy) by DNA staining and flow cytometric analysis. The mitotic inhibitor paclitaxel was used as a reference compound, with or without irradiation, to assess the efficiency of radiation-induced cell cycle arrest. G1 phase arrest was associated only with the presence of the wild-type TP53 gene, but the efficiency of induced arrest varied among the cell lines and the period of G phase arrest appeared to be short. A significant difference (P < 0.002) was also found between the efficiency of induction of G2 phase arrest and the presence of wild-type TP53 gene. The results provide evidence that although the melanoma cell lines generally had an intact TP53 gene, the efficiency of p53 mediated cycle arrest might be deficient and contribute to the resistance of this tumor to treatment. PMID- 11216674 TI - Smad protein expression and activation in transforming growth factor-beta refractory human squamous cell carcinoma cells. AB - In contrast to nonneoplastic keratinocytes, human squamous carcinoma cell lines are able to proliferate in the presence of transforming growth factor-beta (TGF beta) in vitro. This has raised the question whether, how frequently, by which mechanism, and at which stage of development squamous carcinomas escape from TGF beta control in vivo. We have developed a method to rapidly identify the most common molecular alterations in the TGF-beta signaling pathway by combining measurements of the levels and the activation state of Smad signaling intermediates with DNA-based diagnostic assays. In this report, we demonstrate the validity of this approach using a panel of seven squamous cell carcinoma (SCC) lines known to be refractory to TGF-beta-mediated cell cycle arrest. Each of the SCCs expressed the pathway-restricted Smad proteins, Smad2 and-3. Furthermore, treatment with TGF-beta induced phosphorylation of Smad2 in each of the SCCs with the exception of the two cell lines that carry inactivating mutations of the TGF-beta type II receptor. Three of the remaining SCC lines failed to express the common mediator Smad4, two on the basis of loss of transcription and one by a posttranscriptional mechanism. Thus, a mechanism for TGF-beta resistance was identified in five of the seven tumor cell lines. Interestingly, in the two remaining lines, no abnormalities of signaling intermediates were found, and TGF-beta was able to activate TGF-beta-responsive promoters. This suggests that the ability of these two cell lines to grow in the presence of TGF-beta is due to factors extraneous to the TGF-beta pathway itself. Application of our protein-based strategy to interrogate the TGF-beta signaling pathway should allow us to determine whether or not and, if so, how and at which stage human squamous cell carcinomas become TGF-beta resistant in vivo. PMID- 11216675 TI - Update on human rights issues in clinical research. PMID- 11216676 TI - Proximal tibial varus osteotomy. Indications, technique, and five to twenty-one year results. AB - BACKGROUND: Although high tibial osteotomy has been proved effective for the treatment of painful osteoarthritis of the medial compartment of the knee, the role of proximal tibial varus osteotomy for the treatment of painful osteoarthritis of the lateral compartment still remains controversial. METHODS: From 1974 to 1993, we performed proximal tibial varus osteotomy for the treatment of osteoarthritis of the lateral compartment of the knee in thirty-six consecutive patients. The procedure consisted of a proximal lateral opening-wedge varus osteotomy of the tibia with use of corticocancellous bone grafts from the iliac crest. The valgus deformity was posttraumatic in twenty-three patients, followed a lateral meniscectomy in five, was due to overcorrection of a varus deformity in four, and was idiopathic in four. The preoperative valgus deformity averaged 11.6 degrees (range, 4 degrees to 22 degrees ). RESULTS: At a mean of eleven years (range, five to twenty-one years) after the operation, the clinical results for thirty-four of the thirty-six patients were analyzed. None of the patients had severe progression of the osteoarthritis after the osteotomy, and none had a meaningful loss in the range of motion of the knee joint. A superficial wound infection developed in one patient, and another patient had thrombophlebitis. Three patients (9%) had a transient palsy of the peroneal nerve. According to the system of Insall et al., the mean knee score was 84 points (range, 54 to 99 points). According to the knee score described by Lysholm and Gillquist, the subjective result was excellent in nine patients (26%), good in twenty-one (62%), fair in three (9%), and poor in one (3%). CONCLUSIONS: We concluded that when the indications outlined in this study are followed and our opening-wedge technique is used, a proximal lateral opening-wedge varus osteotomy of the tibia is a good alternative for the treatment of isolated osteoarthritis of the lateral compartment of the knee. High accuracy in preoperative planning, based on a slight overcorrection, is important to prevent failure. PMID- 11216677 TI - Bone-grafting for severe patellar bone loss during revision knee arthroplasty. AB - BACKGROUND: Severe patellar bone loss may preclude adequate fixation of another patellar prosthesis as a part of revision knee replacement. The purpose of this study was to describe the surgical technique and early clinical results of an alternative to the conventional treatment options of either patellectomy or retention of the remaining patellar osseous shell. The goals of this procedure are to restore patellar bone stock and potentially to improve the functional outcome. METHODS: Severe patellar bone loss had left a "patellar shell" that precluded insertion of another patellar implant in nine of 100 consecutive knees undergoing revision total knee arthroplasty. Rather than performing a patellectomy or simply retaining the patellar osseous shell in these nine knees (eight patients), I performed a surgical procedure in which a tissue flap was secured to the patellar rim to contain cancellous bone graft inserted into the patellar bone defect. Final follow-up was at a mean of 36.7 months (range, twenty four to fifty-five months) after the patellar bone-grafting procedure. RESULTS: The mean preoperative Knee Society scores for function and pain were 39 points (range, 18 to 82 points) and 40 points (range, 20 to 80 points), respectively. At the time of final follow-up, the Knee Society function and pain scores had improved significantly, to a mean function score of 91 points (range, 80 to 98 points) and a mean pain score of 84 points (range, 65 to 100 points) (p<0.05). The point of greatest patellar thickness measured intraoperatively ranged from 7 to 9 mm. Patellar thickness on immediate postoperative Merchant radiographs averaged 22 mm (range, 20 to 25 mm) whereas, at the time of final follow-up, patellar thickness averaged 19.7 mm (range, 17 to 22.5 mm). CONCLUSIONS: In contrast with other treatment alternatives, this surgical procedure imparts the potential for restoring patellar bone stock and may improve functional outcome by facilitating patellar tracking and improving quadriceps leverage. On the basis of satisfactory short-term to mid-term clinical results, this technique of patellar bone-grafting appears to be an important addition to the armamentarium of surgeons performing revision knee arthroplasties. PMID- 11216678 TI - Lunate excision, capitate osteotomy, and intercarpal arthrodesis for advanced Kienbock disease. Long-term follow-up. AB - BACKGROUND: Kienbock disease is caused by aseptic necrosis of the lunate. In the advanced stages of the disease, carpal collapse, joint incongruity, and osteoarthritis develop. We performed lunate excision, capitate osteotomy, and intercarpal arthrodesis (the modified procedure of Graner et al.) on fifteen patients with stage-IIIB or IV Kienbock disease. This report is a review of the findings in these patients. METHODS: The subjects ranged in age from twenty-six to fifty-four years (mean, 39.2 years) at the time of surgery. We evaluated the results more than five years postoperatively (range, sixty-two to 145 months postoperatively; mean, 79.3 months postoperatively). Therapeutic results were evaluated according to the scoring system of Evans et al. RESULTS: Pain disappeared after surgery in most patients. Others had a reduction in the intensity of the pain to a mild level. The grip strength on the affected side had recovered to about 80% of that on the unaffected side twelve months after surgery. The long-term results were graded as good in eleven of the patients, as fair in two, and as poor in two. Postoperative radiographs showed that the carpal bone parameters (carpal height index and radioscaphoid angle) had improved. Radiographic osteoarthritic changes occurred in all of the patients; however, except for moderate limitation of the range of motion at the wrist joint, these findings did not affect the level of pain, grip strength, or activities of daily living. CONCLUSIONS: Lunate excision followed by capitate osteotomy and intercarpal arthrodesis (the modified procedure of Graner et al.) is a reliable form of treatment for advanced Kienbock disease, with favorable results for at least five years postoperatively. PMID- 11216679 TI - Anterior innominate osteotomy in repair of bladder exstrophy. AB - BACKGROUND: Classic bladder exstrophy is a developmental defect presenting at birth with a wide pubic separation and an exposed bladder; cloacal exstrophy involves, in addition, intestinal prolapse. Reconstruction requires several surgical procedures. The use of anterior iliac osteotomies in this process has not been reviewed in a large series. METHODS: We reviewed the results of eighty six anterior innominate osteotomies performed in conjunction with genitourinary repair of classic and cloacal bladder exstrophy in eighty-two patients. Clinical outcome measures were successful bladder closure, achievement of continence, and maintenance of a normal gait. Radiographs of the pelvis were reviewed, and the pubic intersymphyseal diastasis (a measure of the reduction in tension on the anterior closure) was measured preoperatively and at three time-points postoperatively. Children with classic exstrophy who had undergone osteotomy and bladder neck reconstruction but not bladder augmentation were divided into four groups on the basis of the degree of continence. In addition, children with classic exstrophy were stratified according to age at the time of the osteotomy. The mean postoperative percent reduction in the amount of the original diastasis was determined for all groups. RESULTS: Children with classic exstrophy and those with cloacal exstrophy had correction of the diastasis after the osteotomy, with greater correction in those with classic exstrophy, presumably because of better bone quality. Daytime continence was achieved with anterior osteotomy and bladder neck reconstruction in 74% of the children for whom continence was a goal. However, no difference in the symphyseal diastasis or in the percentage of pubic reduction was detected among the four continence groups. Children who were older at the time of the osteotomy maintained better correction over time. Wound dehiscence or bladder prolapse occurred in 4% of the patients who had osteotomy and primary closure, and the only important complication of the osteotomies was transient palsy of the left femoral nerve in seven children. CONCLUSIONS: Anterior innominate osteotomy is an effective part of reconstructive repair of bladder exstrophy. The primary goals of the osteotomy are to reduce the tension in the closed bladder and the lower abdominal wall and to promote continence by restoring the sling of the pelvic floor muscles. These goals can be achieved in the majority of patients. PMID- 11216680 TI - Diagnosing basilar invagination in the rheumatoid patient. The reliability of radiographic criteria. AB - BACKGROUND: Basilar invagination can be difficult to diagnose with plain radiography in patients with rheumatoid arthritis. Although numerous radiographic criteria have been described, few studies have addressed the reliability of these parameters in the rheumatoid population. The purpose of the present study was to validate and compare the most widely accepted plain radiographic criteria for basilar invagination in this patient population. METHODS: Cervical radiographs of 131 rheumatoid patients were examined. Of these patients, sixty-seven (twenty nine with basilar invagination and thirty-eight without it) were also evaluated with tomograms, magnetic resonance imaging, and/or sagittally reconstructed computed tomography scans to detect the presence of basilar invagination. Three observers who were blinded with regard to the diagnosis independently scored each radiograph as positive, negative, or indeterminate according to the established criteria for invagination proposed by Clark et al., McRae and Barnum, Chamberlain, McGregor, Redlund-Johnell and Pettersson, Ranawat et al., Fischgold and Metzger, and Wackenheim. Interobserver and intraobserver variability, sensitivity, specificity, total percentage of correct results, and negative and positive predictive values were determined for each criterion as well as for various combinations of the criteria. RESULTS: No single test had a sensitivity and a negative predictive value of greater than 90% as well as a reasonable specificity and a reasonable positive predictive value. The combination of the Clark station, the Redlund-Johnell criterion, and the Ranawat criterion, scored as positive for basilar invagination if any of the three were positive, proved to be better than any single criterion; the sensitivity of the combined criteria was 94%, and the negative predictive value was 91%. CONCLUSIONS: A screening test for basilar invagination should have a high sensitivity and a high negative predictive value, so that the disease will not be missed, and yet be specific, so that the disease will not be overdiagnosed. Our data suggest that none of the widely utilized plain radiographic criteria meet these goals. We recommend that measurements be made according to the methods described by Clark et al., Redlund Johnell et al., and Ranawat et al. and, if any of these suggests basilar invagination, tomography or magnetic resonance imaging should be performed. Since approximately 6% of the cases of basilar invagination in rheumatoid patients would still be missed with this approach, tomography or magnetic resonance imaging should be performed on a rheumatoid patient whenever plain radiographs leave any doubt about the diagnosis of basilar invagination. PMID- 11216681 TI - The effects of particulate wear debris, cytokines, and growth factors on the functions of MG-63 osteoblasts. AB - BACKGROUND: Particle-challenged cells release cytokines, chemokines, and eicosanoids, which contribute to periprosthetic osteolysis. The particle-induced activation of macrophages and monocytes has been extensively studied, but only limited information is available on the response of osteoblasts to particulate wear debris. This study examines the effects of particulate wear debris, proinflammatory cytokines, and growth factors on osteoblast functions. METHODS: MG-63 osteoblasts were treated with metal particles (titanium, titanium alloy, and chromium orthophosphate) or polymeric particles (polyethylene and polystyrene) of phagocytosable sizes or were treated with exogenous cytokines and growth factors. The kinetics of particle phagocytosis and the number of engulfed particles were assessed with use of fluoresceinated particles. Cell proliferation was determined according to [3H]-thymidine incorporation, and cell viability was determined by either fluorescein diacetate uptake or trypan blue exclusion. Expressions of osteoblast-specific genes were quantified with Northern blot hybridization, and the secretions of osteoblast-specific proteins and cytokines were analyzed by enzyme-linked immunosorbent assays. RESULTS: MG-63 osteoblasts phagocytosed particles and became saturated after twenty-four hours. A maximum of forty to sixty particles per cell were phagocytosed. Each type of particle significantly suppressed procollagen alpha1[I] gene expression (p<0.05), whereas other osteoblast-specific genes (osteonectin, osteocalcin, and alkaline phosphatase) did not show significant changes. Particle-stimulated osteoblasts released interleukin-6 (p<0.05) and a smaller amount of transforming growth factor-beta1. Particles reduced cell proliferation in a dose-dependent manner without affecting cell viability (p<0.05). Exogenous tumor necrosis factor-alpha also enhanced the release of interleukin-6 (p<0.01) and transforming growth factor-beta1 (p<0.05), whereas the secretion of transforming growth factor-beta1 was increased by insulin-like growth factor-I and prostaglandin E2 as well. Insulin-like growth factor-I and transforming growth factor-beta1 significantly increased procollagen alpha1[I] gene expression in osteoblasts (p<0.05), while tumor necrosis factor-alpha and prostaglandin E2 significantly suppressed procollagen alpha1[I] gene expression (p<0.01). In contrast, neither exogenous nor endogenous interleukin-6 had any effect on other cytokine secretion, on proliferation, or on procollagen alpha1[I] gene expression. The transcription inhibitor actinomycin D reduced both procollagen alpha1[I] transcription and interleukin-6 production. Inhibitors of protein synthesis (cyclohexamide) and intracellular protein transport (brefeldin A and monensin) blocked the release of interleukin-6, but none of these compounds influenced the suppressive effect of titanium on procollagen alpha1[I] gene expression. CONCLUSIONS: MG-63 osteoblasts phagocytose particulate wear debris, and this process induces interleukin-6 production and suppresses type-I collagen synthesis. Osteoblast-derived interleukin-6 may induce osteoclast differentiation and/or activation, but the resorbed bone cannot be replaced by new bone because of diminished osteoblast function (reduced type-I collagen synthesis). Exogenous cytokines (tumor necrosis factor-alpha and interleukin-1beta), growth factors (insulin-like growth factor-I and transforming growth factor-beta1), and prostaglandin E2 can modify particulate-induced alterations of osteoblast functions. PMID- 11216682 TI - Radiocarpal dislocations: classification and proposal for treatment. A review of twenty-seven cases. AB - BACKGROUND: The radiographic characteristics and treatment of radiocarpal dislocation are not well defined. There have been only two reported series of more than eight patients. Thus, there are many questions concerning treatment and functional results. METHODS: Two groups of patients were defined. Group 1 included all patients with pure radiocarpal dislocation and patients with only a fracture of the tip of the radial styloid process. Group 2 included patients with radiocarpal dislocation and an associated fracture of the radial styloid process that involved more than one-third of the width of the scaphoid fossa. A retrospective review and a clinical evaluation were performed. RESULTS: From 1975 to 1998, we observed twenty-seven cases of radiocarpal dislocation. Four were displaced volarly, and twenty-three were displaced dorsally. Fourteen patients presented with associated lesions. Four patients were treated with closed reduction and immobilization in a plaster cast; five, with percutaneous Kirschner wire fixation and cast immobilization; and two, with an external fixator. Eleven patients had open reduction with Kirschner wire fixation and cast immobilization. The seven patients in Group 1 had a highly unstable injury, and four of the seven patients presented with ulnar translation of the carpus. At the time of follow up, at an average of 26.8 months, pronation averaged 76 degrees; supination, 66 degrees; wrist flexion, 54 degrees; wrist extension, 54 degrees; radial inclination, 15 degrees; and ulnar inclination, 18 degrees. The average grip strength was 27 kg. Group 2 included twenty patients. Only thirteen, with dorsal dislocation, were evaluated at the time of follow-up, which averaged fifty-one months. At that time, six reported no pain; four, slight pain; and two, moderate pain. Pronation averaged 63 degrees; supination, 76 degrees; wrist flexion, 51 degrees; wrist extension, 56 degrees; radial inclination, 21 degrees; and ulnar inclination, 39 degrees. Grip strength averaged 38 kg. Seven patients had complications. CONCLUSIONS: On the basis of our experience and a review of the literature, we believe that patients with pure radiocarpal dislocation or with radiocarpal dislocation with a fracture of the tip of the radial styloid process should be treated with reattachment of the ligaments through a volar approach. In patients with radiocarpal dislocation and a fracture of the radial styloid process that involves more than one-third of the width of the scaphoid fossa, the ligaments are still attached to the radial fragment. We believe that in this group of patients, exact articular reduction should be performed through a dorsal approach. Additional studies are needed to support these hypotheses. PMID- 11216683 TI - Long-term results following ankle arthrodesis for post-traumatic arthritis. AB - BACKGROUND: Ankle arthrodesis is considered by many to be the standard operative treatment for end-stage ankle arthritis; however, the long-term effect of ankle arthrodesis on other lower-extremity joints remains largely unknown. The purpose of this study was to perform a clinical and radiographic review to determine the effect of ankle arthrodesis on the development of osteoarthritis in other lower extremity joints. METHODS: Twenty-three patients who had had an isolated ankle arthrodesis for the treatment of painful posttraumatic arthritis of the ankle were followed for a mean of twenty-two years (range, twelve to forty-four years) after the operation. Each completed standardized, self-reported outcome questionnaires (the Foot Function Index, Western Ontario and McMaster University Osteoarthritis Index [WOMAC], and Short Form-36 [SF-36]), was examined clinically by two of the investigators, and underwent complete radiographic examination of the knee, ankle, and foot bilaterally. The radiographic grade of osteoarthritis was determined for each joint, and the levels of overall activity limitation, pain, and disability were determined for each patient from the clinical findings and questionnaire information. RESULTS: Osteoarthritis of the ipsilateral subtalar (p<0.0001), talonavicular (p<0.0001), calcaneocuboid (p<0.0001), naviculocuneiform (p = 0.0012), tarsometatarsal (p = 0.0009), and first metatarsophalangeal joints (p = 0.0012) was consistently more severe than the osteoarthritis of those joints on the contralateral side. Osteoarthritis did not develop more frequently in the ipsilateral knee or lesser metatarsophalangeal joints than it did on the contralateral side. Significant differences between the two sides were found with regard to overall activity limitation (p<0.0001), pain (p<0.0001), and disability (p<0.0001), with the involved side consistently more symptomatic. CONCLUSIONS: To our knowledge, the present series represents the longest follow-up study of ankle arthrodesis to date. Our cohort of patients all had isolated post-traumatic ankle arthritis, and each underwent a successful isolated ankle arthrodesis. At a mean of twenty-two years, the majority of the patients had substantial, and accelerated, arthritic changes in the ipsilateral foot but not the knee. They were often limited functionally by foot pain. Although ankle arthrodesis may provide good early relief of pain, it is associated with premature deterioration of other joints of the foot and eventual arthritis, pain, and dysfunction. PMID- 11216684 TI - Radiographic analysis of low contact stress meniscal bearing total knee replacements. AB - BACKGROUND: Meniscal bearing total knee replacements were developed to decrease the contact stresses on polyethylene and to reduce polyethylene wear. The kinematics of meniscal bearing knee replacements is poorly understood. The present study was designed to evaluate, with radiographic analyses, the motion of the meniscal bearings and the femoral rollback of the Low Contact Stress meniscal bearing knee replacement during knee flexion. METHODS: Eighty-one Low Contact Stress meniscal bearing total knee replacements in seventy-six male patients were assessed on fluoroscopically centered lateral radiographs made with the knee in full extension and in full flexion at an average of six years (range, twenty-four to 147 months) after the operation. The distance and direction of motion of the meniscal bearings and the center contact position of the femoral condyles were measured. Knee evaluations were performed with use of the Knee Society rating system. RESULTS: The average range of motion of the knees, measured on lateral radiographs, was 90 degrees (range, 45 degrees to 136 degrees). As they moved from terminal extension to terminal flexion, thirty-nine knees (48%) exhibited anterior motion of both bearings and sixteen (20%) demonstrated posterior motion of both bearings. Ten knees (12%) had reciprocal motion of the two bearings (one bearing moving anteriorly and one bearing moving posteriorly) with flexion, nine knees (11%) had motion of only one bearing, and seven knees (9%) had no motion of either bearing. When moving from full extension to full flexion, eighteen knees (22%) demonstrated femoral rollback, six knees (7%) showed no change in the position of femoral contact, and fifty-seven knees (70%) exhibited anterior sliding of the femoral condyles. Flexion of the knees demonstrating femoral rollback averaged 104 degrees (range, 76 degrees to 128 degrees), and flexion of the knees demonstrating anterior sliding averaged 94 degrees (range, 45 degrees to 125 degrees). The difference was significant (p = 0.03). According to the Knee Society rating system, the average clinical score for the entire group was 76 points (range, 27 to 100 points) and the average functional score for the entire group was 72 points (range, 30 to 100 points). The average clinical score was 79 points (range, 27 to 98 points) for the knees that exhibited anterior sliding of the femoral condyles and 87 points (range, 52 to 100 points) for those exhibiting femoral rollback (p = 0.09). The average functional scores were 64 points (range, 30 to 100 points) and 72 points (range, 45 to 100 points), respectively (p = 0.15). CONCLUSIONS: Radiographic analysis of meniscal bearing total knee replacements demonstrated an average anterior motion of both the medial and the lateral meniscal bearing of 4.7 mm (range, 1 to 14 mm) in thirty-nine knees (48%) as they moved from terminal extension to terminal flexion. Sixty-three knees (78%) demonstrated no femoral rollback as they were flexed. Knees with anterior sliding of the condyles had a significantly smaller average range of flexion (p = 0.03) and a lower average Knee Society score than did knees demonstrating femoral rollback. We believe that lack of rollback indicates a functional insufficiency of the posterior cruciate ligament. PMID- 11216685 TI - Magnetic resonance imaging of the interosseous membrane of the forearm. AB - BACKGROUND: Diagnosis of damage to the interosseous membrane of the forearm after trauma is difficult. Patients with a proximal radial fracture and associated damage to the interosseous membrane may have wrist pain in association with subluxation or dislocation of the distal radioulnar joint. Accurate identification of injury to the interosseous membrane may allow better planning of surgical treatment. METHODS: T1 and T2-weighted magnetic resonance images that were made in the axial, sagittal, and coronal planes were used to evaluate the interosseous membrane in the forearms of cadavera, volunteers, and patients. The images were evaluated subjectively by two orthopaedic surgeons and a musculoskeletal radiologist. RESULTS: The interosseous membrane was most consistently visualized on the axial images. Axial T2-weighted images showed the interosseous membrane clearly. The addition of fat-suppression techniques allowed abnormalities to be identified more accurately. Fast-spin-echo techniques were used to obtain data quickly and accurately. CONCLUSIONS: The intact and disrupted interosseous membrane can be evaluated with use of magnetic resonance imaging. Axial T2-weighted fast-spin-echo images with fat suppression in the middle one third of the forearm provide the most accurate information. PMID- 11216686 TI - Functional donor-site morbidity during level and uphill gait after a gastrocnemius or soleus muscle-flap procedure. AB - BACKGROUND: There is only limited objective information about functional donor site morbidity after harvest of one head of the triceps surae muscles to cover a severe soft-tissue defect of the leg. The purpose of the present study was to investigate whether a functional deficit is present during level and uphill walking after such a procedure. METHODS: Five subjects who had completely recovered from the initial injury were studied with use of comprehensive gait analysis during free level, fast level, and uphill walking on a ramp at a 10 degrees inclination. RESULTS: Gait analysis revealed no relevant donor-site morbidity affecting level gait at a free walking speed (mean, 1.27 m/sec; range, 1.18 to 1.40 m/sec). When the subjects walked at a higher velocity (mean, 1.89 m/sec; range, 1.58 to 2.43 m/sec), an asymmetry of the ground-reaction forces was seen. The second vertical peak force during push-off was reduced by a mean of 7.3% (range, 0.94% to 12.24%), and the impulse in the direction of progression was reduced by a mean of 8.7% (range, 0.13% to 17.87%) on the affected side (p = 0.04). During uphill walking, a compensatory strategy to reduce the demand on the posterior calf muscles was seen in all subjects-that is, they shortened the length of the step on the contralateral side by a mean of 3.9 cm (range, 2.2 to 6.2 cm), which corresponded to a mean side-to-side difference of 5.6% (range, 2.18% to 6.18%) (p = 0.04). A calcaneal motion pattern, denoted as increased ankle dorsiflexion, was seen in three of the five subjects during uphill walking as a sign of decreased function of the posterior calf muscles. Two of them (both with a soleus flap) also had a calcaneal pattern during fast gait. CONCLUSIONS: We concluded from this study that the functional donor-site morbidity after harvest of one head of the triceps surae muscles is mild in subjects who have had a complete recovery from their initial injury. Normal level gait is possible. However, deficits are seen in more demanding tasks such as fast walking or uphill walking. PMID- 11216687 TI - Altered fibular growth patterns after tibiofibular synostosis in children. AB - BACKGROUND: Iatrogenic synostosis of the tibia and fibula following an operation on the leg in a child has been reported rarely in the literature, and the effects of this complication on future growth, alignment, and function are not known. This is a retrospective case series, from one institution, of crossunions of the distal parts of the tibia and fibula complicating operations on the leg in children. The purpose is to alert surgeons to this possible complication. METHODS: The senior author identified eight cases of iatrogenic tibiofibular synostosis seen in children since 1985. The patients had various diagnoses and were from the practices of four pediatric orthopaedic surgeons. Synostosis developed in six patients after osteotomies of the distal parts of the tibia and fibula, in one after internal fixation of distal tibial and fibular metaphyseal fractures through a single incision, and in one after posterior transfer of the anterior tibialis tendon through the interosseous membrane combined with peroneus brevis transfer to the calcaneus. Medical records were reviewed, and preoperative and follow-up radiographs were analyzed for changes in the relative positions of the proximal and distal tibial and fibular physes and in the alignment of the ankle. RESULTS: Five patients were symptomatic after crossunion; they presented with prominence of the proximal part of the fibula, ankle deformity, or ankle pain. Three patients were asymptomatic, and a synostosis was identified on routine follow-up radiographs. Intraoperative technical errors caused two of the crossunions; the cause of the others was unknown. Following tibiofibular synostosis, growth disturbances were noted radiographically in every patient. The normal growth pattern of distal migration of the fibula relative to the tibia was reversed, resulting in a decreased distance between the proximal physes of the tibia and fibula as well as proximal migration of the distal fibular physis relative to the distal part of the tibia. Shortening of the lateral malleolus led to greater valgus alignment of the ankle. CONCLUSIONS: Tibiofibular synostosis can complicate an operation on the leg in a child. After crossunion, the normal distal movement of the fibula relative to the tibia is disrupted, resulting in shortening of the lateral malleolus and ankle valgus as well as prominence of the fibular head at the knee. The synostosis also interferes with the normal motion that occurs between the tibia and fibula with weight-bearing, potentially leading to ankle pain. PMID- 11216688 TI - Spontaneous resolution of symptomatic post-traumatic cervical epidural hematoma. A case report. PMID- 11216689 TI - The use of low-intensity ultrasound to accelerate the healing of fractures. PMID- 11216690 TI - Design of the Northern Nevada Orthopaedic Trauma Panel: a model, level-II community-hospital system. PMID- 11216691 TI - Report of the 2000 Japanese American Traveling Fellows. PMID- 11216692 TI - The team physician: ethics and enterprise. PMID- 11216693 TI - Timing of femoral fracture stabilization. PMID- 11216694 TI - Postoperative pain in research animals, and use of interbody fusion cages. PMID- 11216695 TI - The semantics of gait mechanics. PMID- 11216696 TI - Second-generation cementing techniques. PMID- 11216697 TI - Fluoroscopic and 3-D computed tomographic guidance in percutaneous fixation of acetabular fractures. PMID- 11216698 TI - Preoperative skin traction was not useful for hip fractures. PMID- 11216699 TI - What's new in sports medicine? PMID- 11216700 TI - Clinical presentation of rhabdoid tumors of the kidney. AB - PURPOSE: We designed this study to differentiate the clinical presentation, particularly the incidence of hematuria, of a rhabdoid tumor of the kidney (RTK), a rare but highly malignant tumor, from a Wilms tumor. PATIENTS AND METHODS: We reviewed patient flow charts from the National Wilms Tumor Study Group and queried participating hospitals to obtain additional information regarding presenting symptoms and laboratory data for fifty patients. Patient ages ranged from 2 days to 3.5 years with a mean of 11 months. We documented the presence of gross and microscopic hematuria, fever, and hypercalcemia. RESULTS: Whereas 75% of children with rhabdoid tumor of the kidney (RTK) had stage III (44%), IV (27%), or V (4%) tumors, 67% of children with Wilms tumors had stage I (41%) or II (26%) tumors. Either gross or microscopic hematuria was present in 84.4% (27/32) of the patients with RTK. Gross hematuria was present in 59% (22/37) of children with RTK compared with 18% previously reported with Wilms tumor. Microscopic hematuria was present in 76% (22/29) of children with RTK compared with 24% previously reported with Wilms tumor. Fever was found in 44% (16/36) of children with RTK, compared with 22% of children previously reported with Wilms tumor. Hypercalcemia was seen 26% (6/23) of children with RTK. CONCLUSION: Although diagnosis of any renal mass still must be confirmed with histopathologic features, a distinct clinical presentation with fever, hematuria, a young age, and high-tumor stage at presentation suggests the diagnosis of RTK. PMID- 11216701 TI - Secondary acute myelogenous leukemia in patients previously treated for childhood renal tumors: a report from the National Wilms Tumor Study Group. AB - PURPOSE: This review characterized cases of secondary acute myelogenous leukemia (AML) occurring after treatment of renal neoplasms on protocols of the National Wilms Tumor Study Group (NWTSG) between October 1969 and December 1991. PATIENTS AND METHODS: The NWTSG database was reviewed for cases of secondary AML and for WT1 status of the affected patients. Referring institutions were contacted by a confidential letter requesting pathology reports, results of immunophenotyping, cytogenetic, and molecular analyses, and details concerning treatment of AML. RESULTS: Of the 5,278 patients treated during the study period, 43 had second malignant neoplasms, and 7 of these 43 had AML. At the time of diagnosis of Wilms tumor, the median age of the seven patients (4 boys) was 3.2 years. Five of the seven renal neoplasms had favorable histologic characteristics. The most common French-American-British morphology was M5. One patient had bilateral tumors, and two were treated for recurrent Wilms tumor. All patients received chemotherapy regimens that included doxorubicin (6) or etoposide (1), and six were treated with infradiaphragmatic irradiation. The median latency period from initial diagnosis of the renal neoplasm to development of secondary AML was 3 years (range, 1.2-4 yrs). One patient had the translocation t(9:11)(p22;q23); WT1 status was not noted for any of the seven patients. CONCLUSIONS: The development of secondary AML in this subset of patients after treatment of renal neoplasms may reflect the interaction of the effects of treatment and possible genetic predisposition toward cancer. PMID- 11216702 TI - Parental health beliefs and compliance with prophylactic penicillin administration in children with sickle cell disease. AB - PURPOSE: Prophylactic penicillin is effective in preventing severe invasive pneumococcal infection in children with sickle cell disease. In some families, compliance has been problematic. The aims of this study were to monitor compliance and to assess the efficacy of the Health Belief Model (HBM) in predicting compliance. METHODS: Fifty mothers of children with sickle cell disease, ages 6 to 60 months, participated in the study. On enrollment, mothers completed surveys assessing their health beliefs regarding sickle cell disease and infections. Compliance was assessed through self-reporting by the mothers and through review of local pharmacy records of penicillin refills. RESULTS: Sixty percent of the mothers reported that they were highly compliant with obtaining the prescribed 14-day refills. Pharmacy records indicated that only 12% actually adhered to this schedule. The self-reports were significantly related to compliance ratings; mothers who admitted less than optimal compliance averaged 42 days between refills, compared with 19 days for mothers who reported good compliance. Varying perceptions identified through the HBM accounted for approximately 30% of the variance in compliance rates. The perceived burdens of picking up the refills and remembering to administer the medication were the most significant factors. CONCLUSIONS: Educational efforts alone are not sufficient to ensure compliance with penicillin prophylaxis. Routinely monitoring compliance through pharmacy records, reviewing parental beliefs about sickle cell disease and infections, and exploring barriers to treatment will promote dialogue about the importance of strict compliance with this relatively simple yet life-saving prophylaxis. PMID- 11216703 TI - Hepatic dysfunction as the presenting feature of acute lymphoblastic leukemia. AB - PURPOSE: Hepatic dysfunction is a rare presentation of leukemia in children. Because most chemotherapy agents are metabolized by the liver, this complication may have major adverse consequences and effective treatment could be compromised. PATIENTS AND METHODS: The MEDLINE database and current management guidelines from the United States Pediatric Cooperative Cancer Groups were reviewed and analyzed. Data from two institutional cases are described. RESULTS: Although previous literature is not informative, our experience suggests that children with leukemia and moderate hepatic dysfunction may tolerate aggressive chemotherapy. CONCLUSION: Current protocol guidelines for dose modification for liver disease may be overly stringent and modification may be beneficial. PMID- 11216704 TI - Hypogammaglobulinemia and reduced numbers of B-cells in children with myelodysplastic syndrome. AB - BACKGROUND: Immunodeficiency in pediatric patients with myelodysplastic syndrome (MDS) has not been described. We report the clinical course of three children with MDS, hypogammaglobulinemia, and reduced numbers of B-cells and B-cell precursors. OBSERVATIONS: Three patients with recurrent infection who were younger than 1-year-old had MDS of the refractory anemia (RA) subtype diagnosed. All had reduced numbers of circulating B-cells and hypogammaglobulinemia. In two patients, cytogenetic studies revealed a monosomy 7 karyotype and bone marrow studies showed decreased numbers of CD34+ progenitor cells and CD 19+ B-cells. Both patients had prolonged courses (7 yrs 10 mos and 6 yrs 9 mos) characterized by recurrent infection and slowly progressive pancytopenia. Both received allogeneic bone marrow transplantation (BMT). The third patient had normal cytogenetic studies and a normal number of CD34+ progenitors but decreased CD19+ B-cells in the bone marrow. She had a stable course with refractory anemia over the course of 7 years. CONCLUSIONS: Pediatric patients with MDS may have hypogammaglobulinemia and reduced numbers of B-cells. These findings do not preclude a relatively stable and prolonged clinical course. Children with newly diagnosed MDS should have an immunologic evaluation in addition to their hematologic assessment. PMID- 11216705 TI - Bilateral breast relapse in acute myelogenous leukemia. AB - We present the case of an 11.5-year-old girl with M1 acute myelogenous leukemia (AML) who had isolated extramedullary relapse develop in both breasts 12 months after diagnosis and 7 months off chemotherapy. She received further chemotherapy, focal radiation therapy, then underwent a matched, unrelated bone marrow transplant and continues in remission 37 months later. Review of the literature revealed 10 cases in other children younger than 21-years-old with AML and breast involvement. These cases are summarized, and potential pathophysiologic mechanisms of spread are discussed. Breast involvement in AML is rare in children. However, regular breast examinations should be performed as part of routine follow-up in all girls with AML. PMID- 11216707 TI - Temporary response of localized intracranial mast cell sarcoma to combination chemotherapy. AB - Cerebral involvement of systemic mastocytosis and intracranial sarcoma of myelogenic origin are well known entities. An 8-year-old girl with an isolated cerebral mast cell tumor is presented. Specific histopathologic stains were used to confirm the diagnosis detecting immunophenotype and proliferative activity. Treatment with irradiation, intrathecal cytarabine, and interferon-alpha2b did not induce regression whereas polychemotherapy did. Systemic combination chemotherapy led to marked transient tumor regression in this proliferating mast cell sarcoma in an unusual intracranial location. PMID- 11216706 TI - Primary central nervous system lymphoma in childhood presenting as progressive panhypopituitarism. AB - We report a 15-year-old boy who had isolated central diabetes insipidus initially diagnosed at age 11 years. A brain magnetic resonance imaging (MRI) was normal at the time. At age 12 years, growth hormone (GH) testing was performed because of a decline in linear growth rate and demonstrated GH deficiency. After a repeat normal brain MRI, GH therapy was begun. Three years later, hormonal testing revealed prepubertal gonadotropins and low testosterone levels, free thyroxine index, and morning cortisol levels. Repeat brain MRI demonstrated a 9-mm enhancing lesion in the region of the pituitary stalk. The pathologic diagnosis was that of a high-grade malignant B-cell lymphoma, suggestive of Burkitt Lymphoma. Growth hormone therapy has not been associated with an increased incidence of lymphoma. This report underscores the need for vigilance in follow up brain imaging and hormonal evaluation in children with diabetes insipidus, especially those with evolving anterior hormone deficiencies. PMID- 11216708 TI - Smooth muscle tumor developing in an immunocompromised child after therapy for leukemia. AB - We report a 5.5-year-old boy who underwent autologous peripheral blood stem cell transplantation for high-risk acute lymphoblastic leukemia and who had two abdominal masses develop 6 months later. Macroscopically complete resection of the abdominal tumors was performed and revealed a well-differentiated leiomyosarcoma. Smooth muscle tumors, benign or malignant, are increasingly recognized in children with various immunodeficiencies; the association with acute lymphoblastic leukemia is rarely described. PMID- 11216709 TI - Tumor lysis syndrome in an infant with Langerhans cell histiocytosis successfully treated using continuous arteriovenous hemofiltration. AB - Langerhans cell histiocytosis (LCH) is an enigmatic disease usually occurring in children. Tumor lysis syndrome (TLS) is a clinical syndrome associated with severe metabolic derangement and oliguric acute renal failure. In this report, we present the clinical course of an infant with advanced LCH who had TLS develop after chemotherapy. Treatment with continuous arteriovenous hemofiltration resulted in effective control of serum uric acid, potassium, creatinine, phosphorus, and blood urea nitrogen levels in the blood. PMID- 11216710 TI - Incomplete cerebral infarctions are not silent. PMID- 11216711 TI - Cyclophosphamide-based, seven-drug hybrid and low-dose involved field radiation for the treatment of childhood and adolescent Hodgkin disease. AB - PURPOSE: The outlook for children and adolescents with Hodgkin disease (HD) is excellent with combined modality therapy. However, the long-term toxicities of multiagent therapy and radiation therapy remain of concern for these patients with curable disease. In an attempt to reduce long-term toxicities while preserving excellent cure rates, we developed a combined-modality protocol using a modified seven-drug hybrid and low-dose (2,000 cGy) involved field radiation therapy (RT). The hybrid used cumulative doses of alkylating agents and anthracyclines that were lower than those used in previous four-drug regimens and substituted a less leukemogenic agent, cyclophosphamide, for nitrogen mustard. PATIENTS AND METHODS: From 1991 through 1994 a cyclophosphamide, vincristine, procarbazine, and prednisone/adriamycin, bleomycin, and vinblastine hybrid was used to treat 29 patients with HD. Median age was 12 years (range 6-16 yrs). Patients who were postpubertal with early stage disease as determined by surgical staging were excluded. Treatment consisted of four cycles of therapy for stages I and IIA, six cycles for stages IIB and III, and eight cycles for stage IV. Twenty two patients also received low-dose RT to areas of bulky disease. RESULTS: Twenty eight patients (97%) had a complete response to chemotherapy. Five patients experienced relapse; two died from disease 27 and 29 months after initial diagnosis; three received additional therapy and are alive with no evidence of disease. Follow-up for all other patients is a median of 56 months (range 24-78 mos) from cessation of therapy and all have remained disease-free. At 5 years follow-up, actuarial disease-free survival is 82%, and the overall survival is 93%. There have been no clinically significant cardiac or pulmonary toxicities and no secondary malignancies. CONCLUSIONS: This therapy has resulted in 5-year overall survival and disease-free survival rates similar to regimens using higher doses of alkylating agents, anthracyclines, and radiation. Longer follow-up will be necessary to fully evaluate disease-free survival, organ damage, and quality of life. PMID- 11216712 TI - Cytochemical staining and flow cytometry methods applied to the diagnosis of acute leukemia in the pediatric population: an assessment of relative usefulness. AB - BACKGROUND: Cytochemical staining has been used in the diagnosis of acute leukemia for more than 20 years. The general availability of flow cytometers and an extensive panel of antibody reagents useful for characterizing blood cell lineage question the usefulness of continuing routine use of the cytochemical staining for the diagnosis of acute leukemia. PATIENTS AND METHODS: Test results were evaluated in 122 (n = 122; 112 with acute lymphocytic leukemia and 10 with acute myeloid leukemia) patients selected from among 320 patients with acute leukemia at Texas Children's Hospital in 1997 and 1998. Results were selected for review if the clinical encounter represented the initial diagnostic work-up and if data were available from cytochemical staining and flow cytometry studies. RESULTS: Cell lineage classification derived from flow cytometry and cytochemical stains were in agreement in all cases. Definitive diagnoses were feasible using flow cytometry results alone in 120 of 122 patients (98.4%) as compared with only 99 of 122 patients (81.2%) when only cytochemical staining results were considered. In two patients with inconclusive flow cytometry results, cytochemical staining alone provided information sufficient for diagnosis. CONCLUSIONS: Results from this study indicate that with few exceptions, flow cytometry studies alone provide sufficient information for diagnosis and management of acute leukemia in children. Nevertheless, cytochemical staining should be available for those cases in which flow cytometry results fail to allow a definitive diagnosis. A modified testing protocol is recommended. PMID- 11216713 TI - Selective use of whole-lung irradiation for patients with Ewing sarcoma family tumors and pulmonary metastases at the time of diagnosis. AB - PURPOSE: The benefit of whole-lung irradiation (WLI) for patients who have pulmonary metastases (PM) of Ewing sarcoma family tumors (ESFT) is unclear. At our institution, WLI is reserved for patients with PM that do not respond completely to induction chemotherapy. We reviewed our experience to assess the impact of WLI on clinical outcome. PATIENTS AND METHODS: Twenty-eight patients with ESFT and PM were treated in three consecutive institutional trials (1979 1996). Extent of pulmonary involvement at diagnosis, response of PM after induction chemotherapy, local treatment of PM thereafter, and clinical outcome were recorded. Treatment included primary tumor surgery and/or radiotherapy and 42 to 58 weeks of multiagent chemotherapy. RESULTS: Only eight patients (29%) received WLI. For the entire study group, the estimated 5-year event-free survival was 22.9% +/- 9.0%; the 5-year survival was 37.3% +/- 9.8%. Complete resolution of PM after induction chemotherapy was not correlated with survival (P = 0.53), nor was treatment with WLI (P = 0.87). CONCLUSIONS: The comparable survival of patients with poor and good response of PM to induction chemotherapy suggests that WLI may benefit poor responders. The use of WLI in good responders may provide similar benefit and merits further study. PMID- 11216714 TI - Use of reverse transcriptase polymerase chain reaction for diagnosis and staging of alveolar rhabdomyosarcoma, Ewing sarcoma family of tumors, and desmoplastic small round cell tumor. AB - PURPOSE: To compare the use of reverse transcriptase polymerase chain reaction (RT-PCR) with that of morphology-based methods for diagnosis, staging, and detection of metastatic disease in pediatric alveolar rhabdomyosarcoma (ARMS), Ewing sarcoma family of tumors (ESFT), and desmoplastic small round cell tumors (DSRCT). MATERIALS AND METHODS: RT-PCR assays for the EWS-FLII, EWS-ERG, PAX3 FKHR, PAX7-FKHR, and EWS-WTI fusion transcripts were performed on RNA extracted from the primary tumor tissue, bone marrow, and body fluids obtained at initial presentation and relapse. Molecular findings were compared with original histologic diagnoses and results of staging procedures. RESULTS: Eighty-eight samples from 47 patients with ARMS (n = 13), ESFT (n = 31), or DSRCT (n = 3) were analyzed. The detection rate of metastatic disease was significantly higher with RT-PCR (95%) as compared with the morphologic methods (70%) for the three pediatric sarcomas studied. In primary tumors with characteristic fusion transcript, RT-PCR was positive in all cases with morphologic evidence of metastatic disease. Moreover, in six patients (3 with ARMS, 2 with DSRCT, and 1 with ESFT) with metastatic disease, micrometastases in bone marrow (4) and other sites (2) were detected by RT-PCR alone. Importantly, none of the patients with localized disease diagnosed had micrometastases detected by RT-PCR in bone marrow. CONCLUSIONS: The high sensitivity and specificity of RT-PCR for the characteristic fusion transcripts of pediatric sarcomas make it an ideal method to aid in the routine staging of these patients. In addition, the 100% sensitivity of RT-PCR in detection of micrometastasis makes it useful for follow up and detection of minimal residual disease. However, the clinical significance of molecularly-detectable disease remains unknown. Further studies should aim to elucidate the therapeutic and prognostic implications of micrometastases detected by RT-PCR alone. PMID- 11216715 TI - Patellar tendon rupture repair using Dall-Miles cable. AB - Ten patients underwent patellar tendon repair with end-to-end suture technique and medial and lateral retinacular repair, as well as reinforcement with a Dall Miles cable through the patella and tibial tubercle. The cable was tensioned at 60 degrees of flexion to allow immediate range of motion to at least 100 degrees of flexion and to protect the repair from undue tension while healing. Accurate tendon length was obtained from a lateral radiograph of the noninvolved knee in 60 degrees of flexion. Patients were allowed to bear full weight as tolerated postoperatively. A knee immobilizer was worn for approximately 2 weeks when adequate muscular control of the leg was attained. The cable was removed 6-8 weeks postoperatively, at which time range of motion equal to the opposite extremity was sought. Full extension was obtained by 1 week postoperatively. Average postoperative knee flexion was 88 degrees at 2 weeks, 112 degrees at 1 month, 133 at 3 months, and 138 degrees at 6 months compared to flexion of 141 degrees in the noninvolved knee. Mean quadriceps muscle strength 1 year postoperatively was 72%+/-11% of the noninvolved leg. No patient had patella infera or rerupture after surgery. Repair of a patellar tendon rupture with end to-end techniques reinforced with a Dall-Miles cable allows immediate rehabilitation without the need for prolonged immobilization. This technique allows restoration of full range of motion early postoperatively and enables patients to regain adequate quadriceps strength. PMID- 11216716 TI - Revision anterior cruciate ligament reconstruction using the lateral third of the ipsilateral patellar tendon after failure of a central-third graft: a preliminary report on 10 patients. AB - Long-term outcomes were reported for 10 (77%) of 13 cases of revision anterior cruciate ligament (ACL) reconstruction using the lateral third of the ipsilateral patellar tendon as a graft. All primary ACL reconstructions were ipsilateral central-third bone-patellar tendon-bone graft procedures. Mean age at follow-up was 30.7 years, and mean time from revision ACL surgery to follow-up was 42.9 months. At follow-up, average KT-1000 difference between knees was 2.4 mm. All patients had a negative pivot shift, extension within 5 degrees of the contralateral knee, and flexion within 15 degrees. Mean bilateral comparison ratios for isokinetic strength and hop testing were: extension, 83.5%; flexion, 96%; and single-leg hop 96.9%. No patella fractures or tendon ruptures had occurred. All patients had returned to their previous work level, and 8 of the 10 patients could participate in at least "moderate" sports activities (e.g., skiing and tennis). The results were comparable to published outcome reports for both primary and revision ACL reconstruction. The lateral third of the ipsilateral patellar tendon is a good graft option for revision ACL reconstruction. PMID- 11216717 TI - Operative versus nonoperative treatment of knee dislocations: a meta-analysis. AB - Although several studies have investigated the optimal treatment of knee dislocations, all have been composed of a small number of patients and therefore have made it difficult to draw definitive conclusions. The literature on knee dislocation was reviewed to allow a meta-analysis and determine whether operative or nonoperative treatment had better outcomes. Range of motion, flexion contracture, Lysholm score, instability, ability to return to preinjury employment, and ability to return to preinjury athletic activities were compared using statistical methods. A total of 132 knee dislocations treated surgically and 74 treated nonoperatively were included. Average range of motion was 123 degrees in the surgical group and 108 degrees in the nonoperative group (P<.001). Flexion contracture averaged 0.5 degrees for the surgical group and 3.5 degrees for the nonoperative group (P<.05). A significant difference (P<.001) also was found in the Lysholm scores, with a surgical group mean of 85.2 and a nonoperative group mean of 66.5. There was no significant difference in the ability to return to preinjury employment or athletic activity or in the amount of instability between the two groups. Surgical treatment appears to be associated with improved outcomes, although significant disability is still possible after successful surgical treatment. PMID- 11216718 TI - Patient demand matching in total knee arthroplasty: is it necessary? AB - Patient demand matching has been accepted as an appropriate method of implant management by hospitals for cost reduction. However, there have been no prospective studies to substantiate whether these patients change their demand levels postoperatively. Theoretically, functional activity levels should not increase significantly postoperatively in patients with preoperative low demand levels for patient demand matching to be effective in avoiding premature prosthetic failure. Preoperative and postoperative demand levels were prospectively reviewed in 279 patients undergoing total knee arthroplasty (TKA). Preoperatively, the medium/high-demand patients performed significantly more activities overall than low-demand patients. Postoperatively, both low- and medium/high-demand patients dramatically increased the number of activities performed. The hypothesis that prosthetic choice should be determined by preoperative activity level (demand matching) was not validated by this study because patient activity levels significantly increased in all categories subsequent to TKA. PMID- 11216719 TI - Surgical aspects of patellar tendonitis: technique and results. AB - Patellar tendonitis is a difficult clinical problem, and surgical treatment remains unclear in its indications, technique, and functional outcome. This article reviews 17 patients (18 knees) with either primary or secondary patellar tendonitis who required operative treatment. Twelve men and 5 women aged 19-50 years comprised the study population. The right knee was involved in 10 patients, and the left knee was involved in 8. Average time from injury to surgery was 24 months, and average postoperative follow-up was 12 months (range: 6-24 months). Criteria were developed for subjective, objective, functional, and overall evaluation. All knees that were operated on were rated as "very abnormal" preoperatively. Postoperatively, 16 (89%) knees were rated as normal or nearly normal, whereas 2 (11%) knees were rated as abnormal. A surgical technique is described, with emphasis on the rationale and technique, and reasons for initial surgical failure and poor functional outcomes are discussed. PMID- 11216720 TI - Nonunion of the tibial tubercle shingle following Fulkerson osteotomy. PMID- 11216721 TI - Fracture of the tibial spine of a Total Condylar III knee prosthesis secondary to malrotation of the femoral component. PMID- 11216722 TI - Primary and delayed exchange for infected total knee arthroplasty. PMID- 11216723 TI - Results of two-stage revision of the infected total knee arthroplasty. PMID- 11216724 TI - Identifying ongoing infection after resection arthroplasty and before second stage reimplantation. PMID- 11216725 TI - Patella fracture after anterior cruciate ligament reconstruction with the patellar tendon: a comparison between different shaped bone block excisions. AB - Tensile failure of a patella after anterior cruciate ligament (ACL) reconstruction with autogenous patellar tendon graft is an uncommon but serious complication. One factor that may affect post-harvest patella strength is the shape of the bony defect. The effect of patella defect shape on ultimate tensile strength and mode of failure of the extensor mechanism has not been studied using physiologic moments. Twelve matched pair knee specimens were randomly distributed within three groups comparing rectangular versus triangular, rectangular versus circular, and circular versus triangular shaped patella defects. Specimens were loaded in tension to failure using physiologic moments. Patella fracture occurred in 21 of 24 specimens. Mean ultimate strength for all patellae with a circular defect was 2540 N (+/-651), rectangular defect was 3267 N (+/-920), and triangular defect was 3009 N (+/-1057). There was no significant difference in mean ultimate tensile strength between defect shapes or between matched pairs within the groups. Mode of failure also was similar in all three groups. No defect shape was found to be superior in this investigation comparing ultimate tensile strength or mode of failure between different shaped patella defects. PMID- 11216726 TI - Acute endocarditis treated with radical debridement and implantation of mechanical or stented bioprosthetic devices. AB - BACKGROUND: Operation for active infective endocarditis carries high mortality and morbidity rates, especially when the annulus is involved. Overall the literature favors the use of autograft and homograft valves because of better resistance to infection. In our clinic during the last 5 years we used an aggressive surgical approach to infective endocarditis in combination with implantation of mechanical or stented bioprosthetic devices. METHODS: From 1994 to 1999, 50 adults with aortic and/or mitral valve endocarditis underwent valve replacement. The median age of the 36 men and 14 women was 58 years (range, 17 to 78 years). All patients had active endocarditis at the time of operation. Native valve endocarditis was present in 48 patients and prosthetic valve endocarditis was present in 2 patients. The aortic valve was affected in 24 patients, the mitral valve in 21 patients, and both the aortic and mitral valves in 5 patients. Two of the patients with mitral endocarditis also had infection of the tricuspid valve. Annular destruction was present in 24 patients (48%). The patients were treated with radical excision of all infected tissue. The annular defects were closed, if possible, with direct sutures. Otherwise, a reconstruction was performed. Follow-up was 100% complete with a median follow-up period of 45 months (range, 6 to 66 months). RESULTS: The procedures were performed without lethal bleeding complications. Early mortality was 12% and the actuarial survival at follow-up was 80%. In none of the patients who died was death related to the prosthetic valve or recurrence of the endocarditis. Only 1 patient (2%) developed recurrence of the infective endocarditis and was reoperated with a Ross procedure. Three and a half years later the patient developed severe valve insufficiency of the autograft and was operated again with implantation of a mechanical device. CONCLUSIONS: Native and prosthetic valve endocarditis can be treated successfully with aggressive surgical debridement and implantation of mechanical or stented bioprosthetic devices with a low risk of recurrent endocarditis. PMID- 11216727 TI - Tricuspid valve replacement with bioprostheses: long-term results and causes of valve dysfunction. AB - BACKGROUND: Although the clinical performance of bioprostheses after valve replacement in the aortic and mitral position has been reported, little is known of the performance of tricuspid bioprostheses. The mechanism of bioprosthetic valve dysfunction after tricuspid valve replacement (TVR) is not clear. METHODS: We reviewed 98 cases of TVR with bioprostheses. To clarify the causes of valve dysfunction, pathologic examination of the explanted valve at the reoperation was performed. RESULTS: Actuarial survival at 18 years was 68.7% +/- 5.8%. There were 12 redo TVRs. In six of the 12 cases, isolated redo TVR was performed. In the other cases, concomitant cardiac procedures were performed. The causes of prosthetic valve dysfunction were pannus formation on the cusps of the right ventricle side (four cases), native valve attachment (two cases), pannus formation + native valve attachment (two cases), sclerotic change (one case), pannus formation + sclerotic change (one case), and native valve attachment + valve infection (one case). Freedom from reoperation, structural valve deterioration, and nonstructural dysfunction at 18 years was 62.7% +/- 10.7%, 96.0% +/- 2.9%, and 76.7% +/- 8.3%, respectively. CONCLUSIONS: In our 18 years of experience, although the survival after TVR with bioprostheses is acceptable, the reoperation free rate is not satisfactory. Pannus formation on the cusps of the ventricular side seems to be a serious problem that causes bioprosthetic dysfunction in the tricuspid position. PMID- 11216728 TI - Temperature during coronary artery bypass surgery affects quality of life. AB - BACKGROUND: The objective of this study was to examine the effects of temperature on a variety of indices of psychologic adjustment and quality of life. METHODS: A total of 209 patients randomly received normothermic (warm) or hypothermic (cold) conditions during coronary artery bypass surgery (CABS), and a number of physical, social, and psychologic measures were assessed before as well as 6 weeks and 6 months after CABS. RESULTS: Repeated measures analyses of covariance revealed significant temperature group main effects for anxiety (p = 0.008) and depression (p = 0.039), with the normothermic group obtaining lower anxiety and depression levels than the hypothermic group at both 6 weeks and 6 months after surgery. Additionally, among patients who entered the study with higher depression levels, those in the hypothermic group tended to have higher depression scores at follow-up compared with patients in the normothermic condition (p = 0.012). No temperature group differences were observed on other quality of life indices. CONCLUSIONS: The results of the present study indicate that hypothermic conditions during CABS are associated with higher levels of emotional distress after CABS than normothermic conditions, particularly for patients with greater stress to begin with. PMID- 11216729 TI - Increased incidence of acute ascending aortic dissection with off-pump aortocoronary bypass surgery? AB - BACKGROUND: An apparent increase in the incidence of acute ascending aortic dissection following off-pump coronary artery bypass grafting (OPCAB) led us to assess retrospectively the rate and circumstances of this complication in our institution on a consecutive series of patients undergoing aortocoronary bypass performed with and without extracorporeal circulation (ECC). METHODS: A retrospective analysis of acute ascending aortic dissections complicating coronary artery bypass grafting surgery in 3,031 patients in our institution since April 1, 1995, was performed using the database of the Montreal Heart Institute. RESULTS: There was a greater frequency of hypertension in the OPCAB group. Iatrogenic acute aortic dissection occurred in 3 patients among 308 operated on without ECC (0.97%) and 1 patient among 2,723 operated on under ECC (0.04%). This difference was statistically significant (p < 0.00001). CONCLUSIONS: The risk of aortic dissection may be increased in OPCAB. Careful manipulation of the aorta with a single side-clamping and a control of the arterial pressure should be used to minimize aortic trauma. High-risk patients should undergo CABG without side-clamping of the aorta or CABG with ECC to prevent this redoubtable complication of myocardial revascularization. PMID- 11216730 TI - Coronary endothelial injury after local occlusion on the human beating heart. AB - BACKGROUND: Occlusion of coronary arteries during beating heart surgery bears the potential for mechanical trauma to the arterial wall with consequent endothelial injury. The aim of this study was to elucidate the effects of local occlusion on the beating heart in human coronary arteries. METHODS: Coronary arteries of patients with dilated cardiomyopathy (n = 7) or ischemic heart disease (n = 10) undergoing heart transplantation were locally occluded after starting cardiopulmonary bypass. Immediately after excision of the diseased heart, the vessels were fixed. Unoccluded segments served as controls. Integrity of endothelial lining was observed with scanning electron microscopy. RESULTS: Scanning electron microscopy revealed significantly more severe endothelial injury in the area of occlusion than in the adjacent, not manipulated control segments. In the region of local occlusion, plaque rupture was noted in three of 34 atherosclerotic vessel specimens, injury to side branches was evident in two of 44, and local microthrombus formation was evident in six of 44 samples. CONCLUSIONS: Local occlusion of human coronary arteries during beating heart coronary surgery may cause focal endothelial denudation, local microthrombosis, atherosclerotic plaque rupture, and injury to target vessel side branches. PMID- 11216731 TI - Left hemispheric strokes in coronary surgery: implications for end-hole aortic cannulas. AB - BACKGROUND: Perioperative stroke (POS) is a devastating complication of coronary artery bypass grafting (CABG). Many studies have been published concerning risk factors and possible causes of POS but none have studied which side of the brain is more frequently involved. The finding of a strong preponderance of left-sided strokes calls into question some widely held theories as to the cause of POS and implicates end-hole aortic perfusion catheters as a major factor. METHODS: During a 3-year period (1996 to 1998), prospective data were collected on all 2,217 consecutive CABG patients at one hospital (with surgery by different surgeons in different groups). Strokes were classified as perioperative (within 3 days of surgery) or late (beyond 3 days but during hospitalization). RESULTS: There were a total of 51 strokes (2.3%): 21 left, 10 right, 7 bilateral, 7 lacunar, 1 brainstem, and 5 indeterminate. There were 18 major territorial perioperative strokes on the left side and 6 on the right side. Thus, 75% (18 of 24) of POS were left-sided. Stroke patients were significantly younger than nonstroke patients (66.3 +/- 10.52 versus 71.4 +/- 8.47 years, p = 0.009). Other demographic data did not differ significantly. CONCLUSIONS: If aortic clamping, cannulation, or manipulation were responsible for most strokes, then right-sided strokes should predominate, as the innominate artery is closest to the source of such emboli. In contrast, end-hole aortic cannulas direct a high-velocity jet at the left carotid orifice and may be responsible for a large proportion of POS. Side-hole aortic cannulas may reduce the incidence of this complication. PMID- 11216732 TI - Direct measurement of nitric oxide release from saphenous vein: abolishment by surgical preparation. AB - BACKGROUND: Surgical preparation (distension) of the saphenous vein (SV) is applied routinely during harvesting in coronary artery bypass grafting (CABG). However, mechanical distension may impair the endothelium, which plays an important role in long-term patency. The present study investigated the effect of surgical preparation of the SV on nitric oxide (NO) release from the endothelium by direct measurement of NO. METHODS: Saphenous vein segments taken from CABG patients were cut open longitudinally and placed in an organ chamber. An NO sensitive electrode and NO meter were used to directly measure NO release induced by acetylcholine (ACh) and bradykinin (BK) from the surgically prepared veins (PV) compared with the control (nondistended) veins. RESULTS: The basal release of NO in the PV group was significantly lower than that in the control group (3.4 +/- 1.4 nM, n = 9 versus 9.9 +/- 2.8 nM, n = 13, p = 0.002). The maximum concentrations of NO release induced by ACh and BK in the PV group were also significantly lower than those in the control veins (for ACh 10(-6) mol/L: 9.6 +/ 3.1 nM, n = 8 versus 41.9 +/- 11.2 nM, n = 12, p = 0.005; for BK 10(-8) mol/L: 8.3 +/- 3.7 nM, n = 7 versus 37.9 +/- 6.1 nM, n = 9, p = 0.003). Further, the duration of NO release in the PV group was significantly shorter than that in control veins (1.5 +/- 1.3 minutes, n = 8 versus 8.1 +/- 1.9 minutes, n = 8, p < 0.001). CONCLUSIONS: Surgical preparation almost abolishes NO release by the SV and this may significantly contribute to the low long-term patency rate of the vein graft. PMID- 11216733 TI - Comparison of systemic vasodilators: effects on flow in internal mammary and radial arteries. AB - BACKGROUND: Spasm is a major concern with the use of arterial conduits in coronary artery bypass surgery (CABG). We evaluated the effect of systemic vasodilators on in vivo radial artery flow compared with internal mammary artery (IMA) flow. METHODS: Fifty patients undergoing primary CABG with a mean age of 69 +/- 5 years enrolled in this study and were randomized to 1 of 5 groups based on the vasodilating agent administered (nitroglycerin, nitroprusside, dobutamine, milrinone, and normal saline as control group). Radial artery and IMA flows, blood pressure, central venous pressure, and heart rate were measured before and 10 minutes after drug administration. RESULTS: Mean arterial pressure decreased significantly after drug administration in both the nitroglycerin (p = 0.007) and nitroprusside (p < 0.001) groups and increased in the dobutamine group (p < 0.001). There were no significant differences between IMA flow or radial flow among the groups before drug administration. A multivariate general linear model was created and revealed drug (specifically nitroglycerin) as the only predictor to increase flow in the IMA (p < 0.001) or the radial artery (p = 0.009). CONCLUSIONS: We conclude that intravenous nitroglycerin causes in vivo vasodilatation of both the IMA and radial artery and is a good systemic vasodilator to be given when harvesting these two conduits. PMID- 11216734 TI - Deep hypothermic circulatory arrest: I. Effects of cooling on electroencephalogram and evoked potentials. AB - BACKGROUND: Deep hypothermia is an important cerebral protectant and is critical in procedures requiring circulatory arrest. The purpose of this study was to determine the factors that influence the neurophysiologic changes during cooling before circulatory arrest, in particular the occurrence of electrocerebral silence. METHODS: In 109 patients undergoing hypothermic circulatory arrest with neurophysiologic monitoring, five electrophysiologic events were selected for detailed study. RESULTS: The mean nasopharyngeal temperature when periodic complexes appeared in the electroencephalogram after cooling was 29.6 degrees C +/- 3 degrees C, electroencephalogram burst-suppression appeared at 24.4 degrees C +/- 4 degrees C, and electrocerebral silence appeared at 17.8 degrees C +/- 4 degrees C. The N20-P22 complex of the somatosensory evoked response disappeared at 21.4 degrees C +/- 4 degrees C, and the somatosensory evoked response N13 wave disappeared at 17.3 degrees C +/- 4 degrees C. The temperatures of these various events were not significantly affected by any patient-specific or surgical variables, although the time to cool to electrocerebral silence was prolonged by high hemoglobin concentrations, low arterial partial pressure of carbon dioxide, and by slow cooling rates. Only 60% of patients demonstrated electrocerebral silence by either a nasopharyngeal temperature of 18 degrees C or a cooling time of 30 minutes. CONCLUSIONS: With the high degree of interpatient variability in these neurophysiologic measures, the only absolute predictors of electrocerebral silence were nasopharyngeal temperature below 12.5 degrees C and cooling longer than 50 minutes. PMID- 11216735 TI - Growth potential of left internal thoracic artery grafts: analysis of angiographic findings. AB - BACKGROUND: The growth potential of the internal thoracic artery (ITA) is still undetermined, and little is known about the long-term effects of anastomosing it to the coronary artery. METHODS: Fifty-three patients whose left ITA (LITA) had been anastomosed to the left anterior descending (LAD) coronary artery underwent coronary angiography within 1 month of operation and in late follow-up (mean interval: 4.5 +/- 1.5 years). The diameter ratios of LITA to LAD were designated as the matching ratio. RESULTS: In follow-up, the diameter of the LITA increased from 1.83 +/- 0.40 to 2.46 +/- 0.53 mm in the 29 patients with progressive proximal native coronary stenosis. However, late results indicate that the matching ratio did not vary according to the location of the LITA anastomosis on the LAD (proximal portion: 1.13 +/- 0.16, distal portion 1.19 +/- 0.13), and reached an upper limit of about 1.4. CONCLUSIONS: Growth potential of the LITA is limited by the diameter of the coronary artery onto which it is anastomosed. The most effective procedure for enhancing the growth potential of the LITA is to anastomose as proximally as possible onto the LAD. PMID- 11216736 TI - The impact of chronic renal failure on atherosclerosis of the internal thoracic arteries. AB - BACKGROUND: Little is known about the impact of renal failure on atherosclerotic changes in the internal thoracic artery (ITA). METHODS: A total of 20 consecutive patients on chronic dialysis who underwent coronary artery bypass grafting (CABG) during April 1998 through September 1999 were investigated. The 20 control patients were selected from the same interval to rigorously match risk factors. Atherosclerosis of the ITA collected from each patient was analyzed using the subjective evaluation proposed by Kay and colleagues. RESULTS: There were no cases of greater than 25% atherosclerotic luminal narrowing among a total of 35 ITA specimens from dialysis patients. The degree of atherosclerosis was not significantly different from that of the specimens from matched patients (p = 0.18). No calcification was found in ITA grafts either microscopically or macroscopically. The number of elastic lamellae, an index of the elasticity of the ITA graft, was not significantly different from those obtained from the matched patients. Analysis of preoperative coronary angiography revealed that coronary calcification was significantly more frequent in dialysis patients (15 patients, 75%) than in matched patients (p < 0.05). By analysis of postoperative angiography in dialysis patients, no evidence of atherosclerotic changes was found in 28 opacified ITAs. In addition, despite the presence of calcification in the native coronary, no calcification was evident along the entire length of the ITAs. CONCLUSIONS: This study revealed the minimal impact of chronic renal failure on atherosclerotic changes in the ITA. The results of this study support the continued use of ITA grafting in dialysis patients. PMID- 11216737 TI - Different CABG methods in patients with chronic obstructive pulmonary disease. AB - BACKGROUND: Pulmonary dysfunction is still a major problem in coronary artery bypass grafting (CABG). The purpose of this randomized study was to determine the effect of different CABG techniques on pulmonary function. METHODS: Fifty eight patients with severe obstructive pulmonary disease had elective isolated coronary surgery. The surgical methods for the patients with chronic obstructive pulmonary disease (COPD) were standard CABG in 18 patients (group 1), beating heart surgery in 19 patients (group 2), and minimally invasive direct coronary artery bypass grafting (MIDCABG) in 21 patients (group 3). RESULTS: The earliest extubation time was from group 3 (p < 0.001). The average stay in the intensive care unit was significantly longer in group 1 (2.6 +/- 1.5 days) than in groups 2 (1.4 +/- 0.8 days) and 3 (1.1 +/- 0.8 days) (p < 0.05). The most prevalent respiratory morbidity was atelectasis that developed in 6 patients from group 1, in 2 patients from group 2, and in 3 patients from group 3. Forced expiratory volumes in 1 second (FEV1) obtained in the second postoperative month were significantly lower than preoperative values only in group 1 (p < 0.05). Forced vital capacity (FVC) values were significantly lower than the preoperative values in all three groups (p < 0.05). CONCLUSIONS: Off-pump bypass surgical procedures are more advantageous than on-pump methods for patients with COPD. These patients can be operated on using the beating heart technique or by using MIDCABG to prevent side effects of CPB on pulmonary function and effects of sternotomy. PMID- 11216738 TI - Ultra-low dose aprotinin decreases transfusion requirements and is cost effective in coronary operations. AB - BACKGROUND: The recommended dose of aprotinin has been shown to reduce blood loss and need for blood transfusions, but the cost precludes its routine use. This study was designed to determine whether a less expensive, ultra-low dose of aprotinin is effective when used in coronary artery bypass grafting with left internal mammary artery. METHODS: Patients (n = 202) were randomized to receive either placebo or aprotinin, 0.5 million KIU before incision and 0.5 million KIU during initiation of cardiopulmonary bypass. Differences in quantity of blood transfused were analyzed. Further groups were analyzed to account for the effect of aspirin. Multivariable analysis was performed to determine risk factors for transfusion. Direct costs of blood products and aprotinin were tabulated for each group. RESULTS: There was an important reduction in the proportion of patients transfused, and number of blood units transfused when aprotinin was given before coronary artery bypass grafting. These differences were even more important in patients on aspirin preoperatively. Independent predictors for increased number of transfusions were aspirin continued before operation, smaller body surface area, and the use of placebo instead of ultra-low dose aprotinin. There was no difference in morbidity between treatment groups. There was a reduction in direct costs associated with the use of aprotinin. CONCLUSIONS: These data support the routine use of aprotinin 1 million KIU in coronary artery bypass grafting with left internal mammary artery to reduce cost and transfusion requirements. PMID- 11216739 TI - Complete revascularization in coronary artery bypass grafting with and without cardiopulmonary bypass. AB - BACKGROUND: The feasibility of complete revascularization on the beating heart without cardiopulmonary bypass (CPB) as compared with the standard operation with CPB in elective low-risk patients with multivessel disease has not been clearly demonstrated in a prospective trial. METHODS: Eighty selected low-risk patients were enrolled. In preoperative study with coronary angiography, the decision was made whether complete revascularization without CPB could be performed. Patients were randomly assigned to receive CABG either with (n = 40) or without CPB (n = 40). Randomization criteria were age, sex, and left ventricular ejection fraction. Completeness of revascularization as well as short- and mid-term clinical outcome in a 13.4 +/- 6.5 month follow-up period were monitored. RESULTS: Twenty-six of 40 (65%) patients undergoing CABG without CPB underwent complete revascularization. In 5 of these patients (12.5%) suitable vessels were discarded for technical reasons and 9 patients (22.5%) were switched to CABG with CPB owing to the deeply intramyocardial course of target vessels (n = 5) or to hemodynamic instability (n = 4). In the group of patients operated on with CPB, 34 of 40 patients (85%) received complete revascularization. In 6 patients (15%) suitable vessels were discarded for technical reasons. Mean number of bypass grafts was 3.1 +/- 0.8 with CPB and 2.6 +/- 0.5 without CPB (p = 0.043). Clinical outcome and hospital stay were comparable in both groups. No patient died during the study period. No myocardial infarction was observed. Three patients undergoing CABG without CPB underwent successful PTCA 3 months after surgery. CONCLUSIONS: CABG without the use of CPB is effective for complete revascularization in the majority of selected low-risk patients. Nevertheless, it has to be stated that the rate of incomplete revascularization in this early series of CABG without CPB is higher, and compromises the basic principle of complete revascularization. PMID- 11216741 TI - Revascularization of severe hibernating myocardium in the beating heart: early hemodynamic and metabolic features. AB - BACKGROUND: We investigated the effects of coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB) in selected patients with severe hibernating myocardium. METHODS: Twelve patients (EF = 25% +/- 0.7%) with reversible ventricular dysfunction (from 2.0 +/- 0.06 to 1.6 +/- 0.05 left ventricular score index by echodobutamine, p < 0.01) in the territory of the left anterior descending artery (LAD) have been studied. Revascularization was achieved by anastomosing the left internal mammary artery to the LAD. The ischemic time of LAD was 9.0 +/- 0.4 minutes. RESULTS: Left ventricular function increased 6 hours and 48 hours after revascularization (left ventricular stroke work index from 32 +/- 1.8 to 42 +/- 1.5 and 40 +/- 0.6 gxm/m2, respectively: p = 0.0001). During the surgical procedure, the heart did not release lactate or creatine phosphokinase. There were no perioperative deaths or severe complications. CONCLUSIONS: Early hemodynamic and metabolic features of CABG without CPB in patients with hibernating myocardium suggest that this procedure is safe and results in a significant improvement of cardiac function without affecting myocardial metabolism. PMID- 11216740 TI - Coronary artery bypass grafting with cardiopulmonary bypass versus off-pump cardiopulmonary bypass grafting: does eliminating the pump reduce morbidity and cost? AB - BACKGROUND: Cardiopulmonary bypass (CPB) may contribute to the complications and cost of coronary artery bypass grafting (CABG). Off-pump CABG (OPCAB) allows coronary revascularization without CPB. We hypothesized that OPCAB provides satisfactory graft patency while reducing complications and cost compared with CABG with CPB. METHODS: We prospectively followed 80 patients undergoing CABG: 40 patients undergoing OPCAB and 40 patients undergoing CABG with CPB. OPCAB patients underwent angiography within 48 hours of surgery to determine early graft patency. Incidence of complications, length of stay, and costs were recorded for each patient. The influence of the number of vessels bypassed was analyzed. RESULTS: OPCAB patients (n = 40) underwent grafting of 2.7 +/- 0.7 vessels per patient compared with 3.6 +/- 0.8 vessels per patient in the CABG with CPB group (n = 40) (p < 0.0001). Angiography demonstrated 105 of 108 (97%) of grafts were patent in the OPCAB group. Incidence of complications, length of stay, and costs did not differ between the OPCAB and CABG with CPB groups. Number of vessels grafted showed a positive correlation to total costs in both groups. CONCLUSIONS: While OPCAB provided satisfactory early graft patency, there was no significant difference between OPCAB and CABG with CPB with regard to cost, length of stay, or incidence of complications. In this study, eliminating CPB did not reduce morbidity or cost after CABG. PMID- 11216742 TI - The radial artery versus the saphenous vein graft in contemporary CABG: a case matched study. AB - BACKGROUND: Although use of the internal thoracic artery has been shown to improve outcomes after coronary artery bypass grafting, the same cannot be said of alternative arterial conduits. To determine the benefit of radial artery (RA) grafting, a case-matched review was undertaken. METHODS: Between March 1994 and March 1999, 2,847 patients underwent isolated coronary artery bypass grafting with a left internal thoracic artery graft, plus saphenous vein grafts (SVGs). Of these patients, 478 also received an RA graft (RA group). The RA patients were matched at a ratio of 1:2 with patients receiving only SVGs and a left internal thoracic artery graft (SVG group; n = 956) using six prognostic risk factors: age, sex, Canadian Cardiovascular Society class, left ventricular grade, number of diseased vessels, and timing of operation. Target vessels were graded according to quality and graftability and were similar between groups. Outcomes were evaluated by univariate and multivariate analyses. RESULTS: There was a significantly higher prevalence of diabetes, hypertension, and peripheral vascular disease in the RA group (p < 0.05). Although stay in the intensive care unit was shorter in the RA group (RA, 30 +/- 2 hours, and SVG, 37 +/- 2 hours; p = 0.0002), total hospital stay was similar between groups. The incidence of perioperative myocardial infarction was higher in the SVG group (SVG, 31 of 956 or 3.2%, and RA, 6 of 478 or 1.3%; p = 0.02). Multivariate analysis revealed RA grafting to be protective against early mortality and morbidity (odds ratio = 0.58; 95% confidence interval, 0.37 to 0.90; p = 0.015) and late mortality and morbidity including late reintervention (risk ratio = 0.60; 95% confidence interval, 0.37 to 0.93; p = 0.02). Actuarial freedom from events at 36 months postoperatively was greater in the RA group (RA, 95% +/- 2%, and SVG, 86% +/- 4%; p = 0.01). CONCLUSIONS: Despite a higher prevalence of preoperative comorbidity, patients in the RA group demonstrated improved outcomes after coronary artery bypass grafting. The RA is a viable and beneficial conduit for this operation. PMID- 11216743 TI - Concomitant subclavian and coronary artery disease. AB - BACKGROUND: Proximal subclavian artery occlusive disease in the presence of a patent internal mammary artery used as a conduit for a coronary artery bypass graft procedure may cause reversal of internal mammary artery flow (coronary subclavian steal) and produce myocardial ischemia. METHODS: We reviewed outcome to determine whether subclavian artery revascularization can provide effective protection from and treatment for coronary-subclavian steal. Between 1985 and 1997, 20 patients had either concomitant subclavian and coronary artery disease diagnosed before operation (group 1, 5 patients) or symptomatic coronary subclavian steal occurring after a previous coronary artery bypass graft procedure (group 2, 15 patients). Patients in group 1 received direct subclavian artery bypass and a simultaneous coronary artery bypass graft procedure in which the ipsilateral internal mammary artery was used for at least one of the bypass conduits. Patients in group 2 received either extrathoracic subclavian-carotid bypass (5 patients, 33.3%) or percutaneous transluminal angioplasty and stenting (10 patients, 66.7%) as treatment for symptomatic coronary-subclavian steal. RESULTS: All patients were symptom-free after intervention. One patient treated with percutaneous transluminal angioplasty and stenting died of progressive renal failure. Follow-up totaled 58.5 patient-years (mean, 3.1 years/patient). In group 1, primary patency was 100% (mean follow-up, 3.7 years). In group 2, one late recurrence was treated by operative revision, yielding a secondary patency rate of 100% (mean follow-up, 2.9 years). CONCLUSIONS: Subclavian artery revascularization can provide effective protection from and treatment for coronary-subclavian steal with acceptably low operative risk. Midterm follow-up demonstrates good patency. PMID- 11216744 TI - Coronary artery fistulas: long-term results of surgical correction. AB - BACKGROUND: Opinions vary as to whether operation should be offered patients with coronary artery fistula, particularly to those who are asymptomatic. Published studies lacked long-term follow-up data. METHODS: We studied 41 patients with coronary artery fistula operated in our unit in the past 30 years with restudies including coronary angiograms in those who agreed to the investigation. RESULTS: There was no operative mortality and operative morbidity was low. The mean duration of follow-up was 9.1 years and 96.9% of the patients were asymptomatic. Twenty-one patients had a coronary angiogram. The native coronary artery either remained dilated and tortuous, or more frequently had thromboses with a short proximal stump. (None of these patients had evidence of myocardial ischemia.) Four patients had demonstrable recurrence fistula but without hemodynamic disturbance. CONCLUSIONS: We advocate operation for all patients with coronary artery fistulas and demonstrable shunting in view of minimal operative risks. Small asymptomatic fistulas without demonstrable shunting should be left alone. The relatively high incidence of residual or recurrent fistula makes long-term follow-up mandatory. PMID- 11216745 TI - Reoperative CABG using left thoracotomy: a tailored strategy. AB - BACKGROUND: Reoperative coronary artery bypass grafting (CABG) through a left thoracotomy is a challenging operation with no one dominant approach. We developed a tailored strategy for this difficult group of patients, integrating the currently available newer technologies for each patient indication. METHODS: Between October 1991 and October 1999, 50 consecutive patients underwent reoperative CABG through a left thoracotomy. Age was 65 +/- 9 years, 40 (80%) were men, and preoperative ejection fraction was 40 +/- 13. In 36 patients (72%) the left internal mammary artery had been placed to the left anterior descending coronary artery during the primary CABG and in 25 of 36 patients (70%) this left internal mammary artery-left anterior descending coronary artery graft was patent. The mean duration from previous CABG was 8.0 +/- 4.8 years. Three approaches were used: (1) conventional cardiopulmonary bypass using fibrillatory or circulatory arrest (n = 33, 66%); (2) Heartport endoaortic balloon occlusion (n = 4, 8%); and (3) off-pump beating heart techniques (n = 13, 26%). RESULTS: The off-pump CABG technique was used in the majority of recent patients and 1 (7.7%) had to be converted to cardiopulmonary bypass due to hemodynamic instability. When cardiopulmonary bypass was used its duration was 122 +/- 59 minutes and mean temperature on bypass was 24 degrees +/- 6 degrees C. In the 4 patients in whom the Heartport system was used, the median endoaortic occlusion duration was 49 minutes. Patients received an average of 1.4 grafts/patient. In 60 of 70 patients (89%) distal anastomoses were performed to an anterolateral coronary target. There were 3 of 50 (6%) operative deaths, 2 in the conventional group and 1 in the endoaortic balloon occlusion group. The mean length of stay in the 47 survivors was 7.8 +/- 3.9 days (median, 7 days). CONCLUSIONS: Reoperative CABG by left thoracotomy remains a challenging operation. Several techniques, including off-pump CABG, conventional cardiopulmonary bypass, circulatory arrest, and endoaortic balloon occlusion, should be in the surgeon's armamentarium to allow a tailored approach for each operation based on patient indications. PMID- 11216746 TI - Surgical strategy for left ventricular free wall rupture after acute myocardial infarction. AB - BACKGROUND: Left ventricular free wall rupture is usually fatal without surgical intervention. However, the most appropriate surgical procedure remains controversial. METHODS: Seventeen patients (14 men, 3 women) who developed left ventricular free wall rupture after acute myocardial infarction were treated surgically. Their mean age was 65.4 years (range, 55 to 79 years). The following surgical procedures were performed: infarctectomy and patch reconstruction in 1 patient, direct closure with or without patch covering in 4 patients, simple patch covering anchored by running suture in 4 patients, and a sutureless technique in 7 patients. Endventricular patch closure was performed in 1 patient with ventricular septal perforation. RESULTS: One of 3 patients with a blow-out type rupture and 1 of 13 patients with an oozing type rupture died shortly after operation. The overall surgical mortality rate was 11.8%. CONCLUSIONS: Selection of the optimal procedure for each cardiac condition is important for obtaining good results. For patients with ongoing squirting bleeding, patch covering is the technique of choice. For oozing, the sutureless technique is preferable. PMID- 11216747 TI - Improved outcomes with an implantable left ventricular assist system: a multicenter study. AB - BACKGROUND: Cumulative experience with the Novacor wearable electric left ventricular assist system (LVAS) now exceeds 850 recipients. The pump inflow conduit (IFC) has been implicated in embolic complications. METHODS: Clinical outcomes were compared for two IFC designs in a retrospective, nonrandomized, multicenter study. The original IFC (woven, unsupported, crimped polyester: control group) and an alternative IFC (knitted, gelatin-sealed, integrally supported, uncrimped polyester: test group) were utilized upon availability in North American and European centers. Differences in cerebral embolism to 180 days postimplant were analyzed. RESULTS: Four hundred ninety patients implanted between August 1996 and August 1999, were studied. Two hundred eighty-eight received the control IFC and 202 received the test IFC. The groups (control, test) were well matched for age (48, 49 years), etiology (idiopathic 53%[152 of 288], 55% [112 of 202]; ischemic 34% [97 of 288], 33% [66 of 202]) and mean observation time (97, 91 days). The incidence of embolic cerebrovascular accidents (CVA) was 21% (60 of 288) in the control and 12% (24 of 202) in the test group (p = 0.010). Independent risk factors for embolic CVA were found to be preimplant acute myocardial infarction (odds ratio 4.3), age above 50 years (odds ratio 2.1), and ischemic etiology (odds ratio 1.7). There was no difference in survival between the groups (71% [205 of 288], 68% [137 of 202]). CONCLUSIONS: The alternative (test) IFC has significantly reduced the incidence of embolic CVA. This improvement is likely due to increased resistance to deformation at implant, improved neointimal adhesion, and more favorable blood flow characteristics within the conduit. PMID- 11216748 TI - When to discontinue extracorporeal membrane oxygenation for postcardiotomy support. AB - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has demonstrated limited success in adult postcardiotomy shock. The goal of this study was to determine when to discontinue ECMO for postcardiotomy support. METHODS: During a 7-year period ECMO was used in 51 postcardiotomy patients, of whom 16 (31%) weaned and 8 (16%) survived. RESULTS: Patients in the heart transplant group were more likely to wean compared with patients in the non-heart transplant group (p = 0.03). Patients aged greater than 65 years (p = 0.04) or with ejection fractions of less than 30% after 48 hours of ECMO (p < 0.001) were less likely to wean. Time on ECMO was significantly longer for survivors in the heart transplant group (101.3 +/- 7.5 hours) compared with survivors in the non-heart transplant group (28.3 +/ 11.9 hours, p < 0.001). CONCLUSIONS: After 48 to 72 hours, consideration should be given to discontinuing ECMO, either by moving to an implantable ventricular assist device or by withdrawal of support, except in those patients with heart transplants. In the latter, both severe postoperative pulmonary hypertension and reperfusion injury may take as long as 120 hours to reverse. PMID- 11216749 TI - A new method of monitoring recovery and weaning the Thoratec left ventricular assist device. AB - BACKGROUND: Recent scientific and clinical data suggest that chronic mechanical ventricular unloading may lead to myocardial recovery. Evaluating and monitoring patients for myocardial recovery and the optimal methods of weaning the left ventricular assist device are not well defined. METHODS: Six patients with advanced heart failure and severe mitral regurgitation have undergone successful bridge to recovery using a Thoratec left ventricular assist device. Data that details their monitoring for myocardial recovery and weaning from the left ventricular assist device were prospectively collected. RESULTS: Clinical data collected during the recovery phase included chest roentgenogram, echocardiography, plasma norepinephrine, tumor necrosis factor-alpha, bioimpedance, and cardiopulmonary exercise testing (peak oxygen consumption). Normalization of these variables with a 10% increase in the peak oxygen consumption was obtained before weaning. The Thoratec device rate and percent systole were manipulated to allow gradual reloading of the ventricle. The weaning process occurred for more than 5 to 10 days to allow time for observation of the ventricle and its response to the increasing workload. CONCLUSIONS: Select patients with advanced congestive heart failure and severe mitral insufficiency can benefit from mechanical device support. We describe our technique of monitoring for myocardial recovery using clinical variables. Our technique of weaning allows for gradual reloading of the ventricle and a longer period of observation before device removal. Additional research is needed to determine which variables will accurately predict long-term myocardial recovery and the optimal weaning method. PMID- 11216750 TI - Effects of metabolic stimulation on cardiac allograft recovery. AB - BACKGROUND: We previously demonstrated that continuous perfusion of cardiac allografts during hypothermic storage with donor blood harvested at the time of organ retrieval improves myocardial recovery after transplantation. However, myocardial metabolism and function remain depressed compared to base line values. This study evaluated the use of a continuous infusion of donor blood enhanced with insulin to augment aerobic myocardial metabolism during and after hypothermic storage. METHODS: Yorkshire pigs (45 to 50 kg) were used to perform 14 orthotopic cardiac transplants using either continuous perfusion with donor blood (blood group, n = 7) or perfusion with donor blood enhanced with 10 IU/L insulin (insulin group, n = 7). After heparinization, hypothermic (4 degrees C) cardioplegic arrest, and donor heart extraction, donor blood (2,844 +/- 210 mL) was harvested in both groups and perfused at room temperature (20 degrees C) at a pressure of 60 mm Hg for 3 hours. Blood cardioplegia was delivered after each anastomosis in both groups and arterial and coronary sinus blood samples were obtained to examine myocardial metabolism. A Millar micromanometer was used to measure left ventricular developed pressure and the rate-pressure product at varying preloads. RESULTS: There were no differences in either myocardial lactate or acid release between the two groups. Hearts in the insulin group displayed higher myocardial oxygen extraction than those in the blood group. The recovery of developed pressure was higher in the insulin group compared to the blood group (91% +/- 19% vs 73% +/- 2%, p = 0.04). CONCLUSIONS: In this model, continuous perfusion of cardiac allografts with donor blood and insulin preserves myocardial metabolism during hypothermic storage and improves metabolic and functional recovery after orthotopic cardiac transplantation. PMID- 11216751 TI - Deep hypothermic circulatory arrest: II. Changes in electroencephalogram and evoked potentials during rewarming. AB - BACKGROUND: Electrophysiologic studies during rewarming after deep hypothermic circulatory arrest probe the state of the brain during this critical period and may provide insight into the neurological effects of circulatory arrest and the neurologic outcome. METHODS: Electroencephalogram (EEG) and evoked potentials were monitored during rewarming in 109 patients undergoing aortic surgery with hypothermic circulatory arrest. RESULTS: The sequence of neurophysiologic events during rewarming did not mirror the events during cooling. The evoked potentials recovered first followed by EEG burst-suppression and then continuous EEG. The time to recovery of the evoked potentials N20-P22 complex was significantly correlated with the time of circulatory arrest even in patients without postoperative neurologic deficits (r = 0.37, (p = 0.002). The nasopharyngeal temperatures at which continuous EEG activity and the N20-P22 complex returned were strongly correlated (r = 0.44, p = 0.0002; r = 0.41, p = 0.00003) with postoperative neurologic impairment. Specifically, the relative risk for postoperative neurologic impairment increased by a factor of 1.56 (95% CI 1.1 to 2.2) for every degree increase in temperature at which the EEG first became continuous. CONCLUSIONS: No trend toward shortened recovery times or improved neurologic outcome was noted with lower temperatures at circulatory arrest, indicating that the process of cooling to electrocerebral silence produced a relatively uniform degree of cerebral protection, independent of the actual nasopharyngeal temperature. PMID- 11216752 TI - Induction of inflammatory mediators during reperfusion of the human heart. AB - BACKGROUND: Cardioplegia and reperfusion may induce an inflammatory reaction, which may contribute to postoperative morbidity and mortality. METHODS: Gene expression of cytokines, adhesion molecules, and vasoactive substances was evaluated in left ventricular biopsies taken before cardioplegia (lasting approximately 70 minutes) and after reperfusion (approximately 40 minutes) from 19 patients (5 with valvular or combined disease, 7 with stable angina pectoris, 7 with unstable angina). mRNA was extracted and amplified with a semiquantitative reverse transcription polymerase chain reaction. RESULTS: Cardioplegia reperfusion increased mRNA for E-selectin by a factor of 17 +/- 5 (p < 0.002) (mean +/- SEM), interleukin-1beta, with 9 +/- 3 (p < 0.007), tumor necrosis factor-alpha with 6 +/- 3 (p < 0.05), interleukin-2 receptor alpha chain CD25 with 2 +/- 0.6 (p < 0.04), and intercellular adhesion molecule-1 with 2 +/- 0.4 (p < 0.005). Before cardioplegia, mRNA for endothelial nitric oxide synthase was predominantly detected in unstable angina patients, and increased by a factor of 11 +/- 6 (p < 0.02) during reperfusion. mRNA for endothelin-1 decreased by a factor of 0.5 +/- 0.1 (p < 0.0005). The changes were more pronounced in unstable patients. The transcription factor nuclear factor kappa B (NFkappaB), which regulates expression of inflammatory mediators, was activated during reperfusion (n = 10, p < 0.0001). CONCLUSIONS: Open heart surgery induces an inflammatory response in the human heart, which is more pronounced in patients with unstable angina. It involves NFkappaB activation and expression of several NFkappaB regulated genes. PMID- 11216753 TI - Beta-chemokine secretion patterns in relation to clinical course and outcome in children after cardiopulmonary bypass: continuing the search to abrogate systemic inflammatory response. AB - BACKGROUND: Surgery involving cardiopulmonary bypass (CPB) is frequently accompanied by a systemic inflammatory response partly triggered by neutrophils and monocyte-macrophages. Certain cytokines that are powerful leukocyte chemotactic factors have recently been characterized and shown to be important in evoking inflammatory responses: monocyte chemoattractant protein-1 (MCP-1) has monocyte-macrophage chemotactic activity, and regulated-upon-activation normal T cell expressed and secreted (RANTES) has a potent chemoattractant activity for mononuclear phagocytes. This prospective cohort study investigated possible roles of these chemokines in the inflammatory response to CPB and relationships between the changes in chemokine levels and the clinical course and outcome. METHODS: Systemic blood of 16 children undergoing CPB was collected after induction of anesthesia (base line); at 15 minutes after bypass onset; at CPB cessation; and at 1, 2, 4, 8, 12, and 24 hours afterward to measure MCP-1 and RANTES. RESULTS: The significant changes of plasma beta chemokine levels following CPB were associated with patient characteristics, operative variables, and postoperative course. Cardiopulmonary bypass of more than 2 hours, longer surgical times, inotropic support, and reoperation were associated with higher MCP-1 levels and lower RANTES levels. CONCLUSIONS: Our results suggest a relation between CPB induced mediators and clinical effects, implying pathogenic roles for chemokines following CPB. These molecules should be considered as possible targets for therapeutic intervention. PMID- 11216754 TI - Effects of a platelet-activating factor antagonist on lung injury and ventilation after cardiac operation. AB - BACKGROUND: Platelet-activating factor is a mediator of lung injury during cardiac operation. Platelet-activating factor antagonists reduce lung injury in animal models of cardiopulmonary bypass but there is no confirmatory evidence in clinical practice. METHODS: The effect of a low or high dose of a platelet activating factor antagonist (Lexipafant) was assessed in a single center, double blind, placebo-controlled, parallel group study. One hundred fifty patients undergoing coronary artery bypass grafting were randomized by minimization into three groups to receive placebo infusion, 10 or 100 mg of lexipafant for over 24 hours. Serial arterial oxygen and carbon dioxide tension, alveolar arterial oxygen gradient, and percent saturation were measured before operation and at 1, 6, 24, 48 hours, and 5 days after operation. RESULTS: Patient groups were similar with respect to age, sex, body surface area, and urgency of operation. Likewise, the groups were similar with respect to duration of cardiopulmonary bypass and the number and type of grafts. Maximum lung injury occurred at 48 hours when the arterial oxygen tension and percent saturation reached a nadir (both p < 0.001) accompanied by the maximum increase in the alveolar arterial gradient (p < 0.001). All measurements demonstrated partial recovery by 5 days but remained significantly (p < 0.001) impaired in comparison to baseline values. Duration of ventilation was similar in all groups. Lexipafant, at low or high dose, did not moderate lung injury after cardiopulmonary bypass and did not influence the duration of postoperative ventilation. CONCLUSIONS: Despite experimental and clinical evidence implicating platelet-activating factor in the pathophysiology of lung injury after cardiopulmonary bypass, no beneficial effect of a platelet activating factor antagonist on lung function or ventilation could be demonstrated in this clinical trial. PMID- 11216755 TI - Morphometric identification of luminal narrowing of myocardial capillaries after cardioplegic arrest. AB - BACKGROUND: Because there is no smooth muscle cell surrounding the capillary endothelial cells, the effect of coronary microcirculation at the capillary level following cardioplegic arrest and reperfusion would be much different from that of resistant arterioles. We therefore studied the effect of hypothermic blood cardioplegic arrest and subsequent reperfusion on the myocardial capillaries in cardiac operation patients. METHODS: Twenty-seven patients who underwent cardiac operations were included in this study. Three sequential biopsies (preischemia, ischemia, and reperfusion) were obtained from the right atrium. This study was restricted to blood vessels with a diameter of less than 8 microns. Ten randomly selected capillaries from each biopsy were measured for luminal surface area, endothelial cytoplasmic surface area, and total cross-sectional surface area of capillaries. RESULTS: From stereologic morphometric studies, the serial changes in total cross-sectional surface area were not statistically significant (p = 0.152). However, there was a significant swelling of endothelial cytoplasm following ischemia and reperfusion (p = 0.0007). Meanwhile, changes in luminal surface area of capillaries following ischemia and reperfusion were also remarkable (p = 0.0008). CONCLUSIONS: The most striking finding of this study was the progressive decrease in capillary lumen during ischemia and after reperfusion. The swelling of endothelial cells is a major determinant of luminal narrowing of capillaries in patients receiving cardioplegic arrest. PMID- 11216756 TI - Retrograde versus antegrade crystalloid cardioplegia in coronary surgery: value of troponin-I measurement. AB - BACKGROUND: The optimal route for delivery of cardioplegia is still in debate in patients with ischemic heart disease. Cardiac troponin-I is a new marker with the potential for detection of minor differences in myocardial ischemia. METHODS: In a prospective randomized trial 58 patients undergoing elective coronary artery bypass grafting for two- or three-vessel coronary artery disease were divided into groups with antegrade (group A, n = 29) and retrograde (group R, n = 29) application of crystalloid cardioplegia (St. Thomas II). Patients with major risk factors were excluded. In addition to routine electrocardiogram monitoring, cardiac troponin-I and creatine kinase-MB activity were measured in all patients preoperatively at 2, 5, 8, 24, and 48 hours after aortic cross-clamp release, and at hospital discharge. RESULTS: In both groups, there were no differences regarding operative parameters. A significantly higher cardiac troponin-I concentration was observed in the antegrade group at 24 hours after cross-clamp (8.2 +/- 8.5 microg/L vs 3.2 +/- 3.1 microg/L; p = 0.02). Patients with subtotal stenosis or occlusion of one or more main coronary arteries showed significantly lower cardiac troponin-I levels after retrograde application. CONCLUSIONS: Lower concentrations of the cardiac troponin-I marker after retrograde application of cardioplegia indicate advantages of myocardial protection in ischemic heart disease. PMID- 11216757 TI - Effects of carnitine on cardiac function after cardioplegic ischemia in neonatal rabbit hearts. AB - BACKGROUND: Ischemia immediately impairs myocardial fatty acid metabolism and reduces the concentration of carnitine which is an essential cofactor for fatty acid metabolism in the mitochondria. The purpose of this study was to investigate the effects of carnitine administration on recovery of cardiac function after cardioplegic ischemia in the neonatal heart where fatty acid metabolism is not a predominant source of adenosine triphosphate. METHODS: Isolated blood-perfused neonatal rabbit hearts underwent 3 hours of cold cardioplegic ischemia. The control group (n = 10) was reperfused with unmodified diluted blood. The carnitine group (n = 10) was reperfused with the blood containing 5 mM/L of carnitine. Before ischemia (base line) and after 15 and 30 minutes reperfusion, left ventricular (LV) function and LV compliance were measured using a intraventricular conductance catheter combined with an isovolumic balloon. Coronary blood flow was measured and myocardial oxygen consumption was calculated. RESULTS: Carnitine significantly improved not only LV systolic function but also LV diastolic function (p < 0.05) as well as LV compliance after ischemia. Coronary blood flow and myocardial oxygen consumption were significantly improved after ischemia in the carnitine group compared with the control group (p < 0.05). CONCLUSIONS: These results suggest that carnitine strikingly improves LV functional recovery and aerobic metabolism after cold cardioplegic arrest, and may improve cardiac performance in neonates after open heart surgery. PMID- 11216758 TI - Hierarchy of regional oxygen delivery during cardiopulmonary bypass. AB - BACKGROUND: Relative to the nonbypass state, cardiopulmonary bypass may decrease whole-body oxygen (O2) delivery. We predicted that during cardiopulmonary bypass, a hierarchy of regional blood flow and O2 delivery could be characterized. METHODS: In 8 46.5 +/- 1.2-kg pigs, fluorescent microspheres were used to determine blood flow and O2 delivery to five organ beds before and during 37 degrees C cardiopulmonary bypass at four randomized bypass flows (1.4, 1.7, 2.0, and 2.3 L/min/m2). At completion, 18 tissue samples were obtained from the cerebral cortex (n = 4), renal cortex (n = 2), renal medulla (n = 2), pancreas (n = 3), small bowel (n = 3), and limb muscle (n = 4) for regional blood flow determination. RESULTS: At conventional cardiopulmonary bypass flow (2.3 L/min/m2), whole-body O2 delivery was reduced by 44 +/- 6% relative to the pre cardiopulmonary bypass state (p < 0.05). Over a range of cardiopulmonary bypass flows (2.3 to 1.7 L/min/m2), brain and kidney maintained their perfusion. Blood flow and O2 delivery to both regions were reduced when the cardiopulmonary bypass flow was reduced to 1.4 L/min/m2. However, perfusion and O2 delivery to other visceral organs (pancreas, small bowel) and skeletal muscle showed pump flow dependency over the range of flows tested. CONCLUSIONS: This study characterizes the organ-specific hierarchy of blood flow and O2 distribution during cardiopulmonary bypass. These dynamics are relevant to clinical decisions for perfusion management. PMID- 11216759 TI - Short ischemia causes endothelial dysfunction in porcine coronary vessels in an in vivo model. AB - BACKGROUND: The aim of this study was to evaluate the effects of a short period of ischemia (10 mins) and a prolonged period of ischemia (60 mins) followed by reperfusion on coronary flow changes induced by acetylcholine (ACh), adenosine (ADO), and endothelin (ET). METHODS: The left anterior descending coronary artery in anesthetized pigs was occluded for 10 or 60 minutes followed by 120 minutes reperfusion. Thereafter, the flow changes in the left anterior descending coronary artery were studied after intracoronary infusion of ACh, ADO, and ET. RESULTS: Short-term ischemia (10 minutes) caused a decrease in vasodilatation, but not the vasoconstriction response to ACh. Prolonged ischemia (60 minutes) impaired ADO induced vasodilatation and aggravated ET evoked vasoconstriction. CONCLUSIONS: The present findings suggest that a short period of ischemia (10 minutes) causes disturbances of the endothelial regulation of coronary vascular tone and that this endothelial regulation is more sensitive, and precedes changes in vascular smooth muscle function after ischemia and reperfusion. PMID- 11216760 TI - Safety and efficacy of a heparin removal device: a prospective randomized preclinical outcomes study. AB - BACKGROUND: Systemic protamine sulfate for heparin reversal after cardiopulmonary bypass (CPB) is associated with uncommon, but life-threatening adverse reactions. METHODS: In a prospective randomized 3-day outcomes study, a heparin removal device (HRD) group (n = 12; 60-, 80-, 100-kg subgroups) was compared with a matched systemic Protamine group (Protamine; n = 6) for safety and efficacy using an adult swine model of CPB (60 minutes, 28 degrees C). RESULTS: HRD run time was 25 to 38 minutes depending on weight without complications. After HRD, heparin concentration decreased from 4.77 +/- 0.17 to 0.45 +/- 0.06 U/mL (activated clotting time [ACT] 776 +/- 83 to 180 +/- 12 seconds), and in Protamine, 3.94 +/- 0.63 to 0.13 +/- 0.02 U/mL (ACT 694 +/- 132 to 101 +/- 5 seconds) (p = 0.01 between groups, but no significant differences 60 minutes later). No significant difference between HRD and Protamine to 72 hours was seen in plasma-free hemoglobin C3a, heparin concentration, thromboelastogram index, platelet count, activated partial thromboplastin time, anti-thrombin III, fibrinogen, ACT, and tissue histology. CONCLUSIONS: In a prospective randomized outcomes study, HRD achieved predictable reversal of systemic heparinization after CPB with no difference in safety or outcomes compared with protamine. PMID- 11216761 TI - Posttransplant function of a nonbeating heart is predictable by an ex vivo perfusion method. AB - BACKGROUND: We attempted to predict the posttransplant cardiac function of nonbeating donor hearts. METHODS: A total of 13 dogs were studied. Hearts were left in situ for 45 minutes after cardiac arrest caused by exsanguination. Hearts were then excised and reperfused in an ex vivo perfusion apparatus after 60 minutes of warm ischemia to test whether they could eject against an 80 mm Hg afterload from a preload of 10 mm Hg. Thereafter, all hearts were transplanted orthotopically. RESULTS: Four of 13 hearts were able to eject in the apparatus (group A). However, the other nine hearts could not eject under the defined conditions (group B). All four hearts in group A showed good posttransplant hemodynamics (systolic arterial pressure > 80 mm Hg with mean left atrial pressure < 10 mm Hg) without dopamine. However, none of nine hearts in group B could support the circulation without dopamine. CONCLUSIONS: Nonbeating donor heart function evaluated in the perfusion apparatus predicts posttransplant heart function. This method may be applicable for selection of transplantable hearts from nonbeating heart donors. PMID- 11216762 TI - Increased coronary artery blood flow with aortomyoplasty in chronic heart failure. AB - BACKGROUND: We hypothesized that diastolic counter-pulsation using aortomyoplasty will increase coronary blood flow. METHODS: In dogs (n = 6, 20 to 25 kg), the left latissimus dorsi muscle was isolated, wrapped around the descending thoracic aorta, and conditioned by chronic electrical stimulation. Heart failure was induced by rapid ventricular pacing. In a terminal study, left ventricular and aortic pressures, and blood flow in the left anterior descending coronary artery and descending aorta were measured. The endocardial-viability ratio was calculated. RESULTS: Aortomyoplasty increased mean diastolic aortic pressure (70 +/- 5 to 75 +/- 5 mm Hg, p < 0.05) and reduced peak left ventricular pressure (86 +/- 4 to 84 +/- 4 mm Hg, p < 0.05), leading to a 16% increase in endocardial viability ratio (1.29 +/- 0.05 to 1.49 +/- 0.05, p < 0.05). Coronary blood flow was increased by 15% (8.2 +/- 1.5 to 9.4 +/- 1.6 mL/min, p < 0.05). During muscle contraction, 2.7 +/- 0.5 mL was ejected from the wrapped aortic segment. CONCLUSIONS: These data demonstrate that aortomyoplasty provides successful diastolic counterpulsation after muscle conditioning and heart failure. PMID- 11216763 TI - Thoracic and thoracoabdominal aneurysm repair under deep hypothermia using subclavian arterial perfusion. AB - BACKGROUND: Hypothermic circulatory arrest is a valuable adjunct for thoracic and thoracoabdominal aortic aneurysm repair. Retrograde aortic perfusion through the femoral artery, however, carries a risk of cerebral embolism or malperfusion. To avoid these complications we adopted antegrade aortic perfusion through a prosthetic graft attached to the left subclavian artery through a left thoracotomy. METHODS: Ten patients had repair of descending thoracic and thoracoabdominal aortic aneurysm under deep hypothermia with antegrade aortic perfusion through the left subclavian artery. Hypothermic circulatory arrest was used because proximal aortic control was hazardous due to rupture or intraluminal disease, or for spinal cord protection. RESULTS: There was no brain injury and one hospital death. The cause of death was massive bleeding from the gastrointestinal tract not related to deep hypothermia or the perfusion method. All 9 survivors were alive and well after a mean follow-up period of 9 months. CONCLUSIONS: Using the left subclavian artery as a site of aortic perfusion can avoid retrograde aortic perfusion, hence reducing the potential for brain injury due to embolic stroke or malperfusion through a dissected thoracoabdominal aorta. PMID- 11216764 TI - Evaluation of lymph node metastases in squamous cell carcinoma of the esophagus with positron emission tomography. AB - BACKGROUND: Previous studies suggest positron emission tomography (PET) may improve staging accuracy of esophageal cancer compared with conventional methods, especially in detecting occult distant metastases. We evaluated the accuracy of PET in the detection of lymph node metastasis prospectively with pathologic findings. METHODS: Fifty-three patients with squamous cell carcinoma underwent whole-body PET scan and chest computed tomography (CT). The findings of PET and chest CT of 50 patients who underwent curative esophagectomy with radical lymph node dissection were compared with the pathologic findings. RESULTS: Among 53 primary esophageal tumors, PET detected 51 (96.2%) and CT detected 49 (92.5%) tumors correctly. Nodal metastases were present in 108 of 436 dissected lymph node groups. PET detected 56 metastatic node groups (51.9% sensitivity, 94.2% specificity, 83.7% accuracy), compared with CT, which detected 16 (14.8% sensitivity, 96.7% specificity, 76.6% accuracy; sensitivity: p < 0.005). CONCLUSIONS: PET was more sensitive than CT in the detection of nodal metastases and may improve staging of squamous cell carcinoma of the esophagus. PMID- 11216765 TI - Induction of MAGE-3 expression in lung and esophageal cancer cells. AB - BACKGROUND: Although MAGE-3 has been detected in approximately 40% of lung and esophageal cancers, expression of this cancer testis antigen appears to be below the threshold for immune recognition in patients with these malignancies. The aim of this study was to determine if the demethylating agent, 5-Aza-2'-deoxycytidine (DAC) and if the histone deacetylase inhibitor Depsipeptide FR901228 (DP) could enhance MAGE-3 expression in lung and esophageal cancer cells. METHODS: Eleven lung and esophageal cancer lines and cultured normal human bronchial epithelial (NHBE) cells were exposed to normal media (NM), DAC, DP, or combination DAC/DP at varying concentrations and exposure durations. MAGE-3 expression was evaluated by quantitative RT-PCR (TaqMan) and immunohistochemistry techniques. Trypan blue exclusion techniques were used to examine the proliferation of cancer cells after drug exposure. RESULTS: Relative to untreated controls, MAGE-3 expression was enhanced 32-fold (range 3.9 to 110) by DAC alone (0.1 micromol/L x 72 h), 2.1 fold (0.4 to 4.2) by DP alone (25 ng/mL x 6h), and 57-fold (4.6 to 209) by sequential DAC/DP exposure. Increased MAGE-3 mRNA copy numbers coincided with enhanced protein levels in these cells. MAGE-3 expression persisted after drug exposure. Flow cytometry confirmed the presence of functional HLA class I expression in these cells. Sequential DAC/DP treatment mediated pronounced growth inhibition in cancer cells but not NHBE. CONCLUSIONS: Sequential DAC/DP treatment may be a novel strategy to simultaneously augment MAGE-3 expression and induce growth arrest in thoracic malignancies. PMID- 11216766 TI - Colon interposition for esophageal replacement: isoperistaltic or antiperistaltic? Experimental results. AB - BACKGROUND: Isoperistaltic colon is preferred to antiperistaltic colon for esophageal replacement, but experimental data do not exist to support this practice. METHODS: In 7 dogs a 20 cm long colon loop was interposed between the skin and the small bowel, isoperistaltically in 3 dogs and antiperistaltically in 4 dogs. Three months later five strain-gauges were implanted and evacuation was investigated by motility testing, barium studies, and scintigraphy. RESULTS: Motility recording showed normal colon motility in the excluded loops. Quiescent states (duration 40.2 +/- 13.6 minutes) were followed by contractile states (duration 7.5 +/- 2.4 minutes, frequency 3.3 +/- 0.6 per minute). The main peristaltic direction of isoperistaltic loops was isoperistaltic, and the main peristaltic direction of antiperistaltic loops was antiperistaltic. Evacuation took place exclusively during the contractile status. Half time emptying was more rapid in isoperistaltic loops (35 +/- 11 vs 69 +/- 16 minutes). The content of antiperistaltic loops was held back by antiperistaltic activity. Application of oatmeal porridge into the loops shortened the quiescent status from 40.2 to 13.2 +/- 4.8 minutes. CONCLUSIONS: The colon graft for esophageal replacement is an active system. Food is stored during the quiescent states and evacuated during the contractile states. The original peristaltic direction is preserved so that retroperistalsis in antiperistaltic loops may lead to patient discomfort and pulmonary complications. PMID- 11216767 TI - Survival after resection of metachronous non-small cell lung cancer in 127 patients. AB - BACKGROUND: In a number of patients with treated primary non-small cell lung cancer (NSCLC) a second primary tumor will be diagnosed. Our experience with surgery in these patients was analyzed and possible prognostic parameters were defined. METHODS: Patients with metachronous NSCLC (n = 127) who underwent resection from 1970 through 1997 were analyzed. All tumors were classified postsurgically. Median interval between the tumors was 3.7 years. Actuarial survival time was estimated and risk factors influencing survival were evaluated. RESULTS: Overall 5-year survival after the first resection was 70% and after the second resection was 26%. Patients with stage IA of the second primary tumor did have a significantly better survival (p < 0.005) as compared with patients with higher staged second primaries. Stage of second primary tumor and age were significant predictors of survival, whereas stage of first tumor, interval between resections, histology, and type of resection were not. CONCLUSIONS: Survival of patients with metachronous NSCLC and resection of both tumors is high, but poorer than after resection of the first tumor. Irrespective of the interval, patients with stage IA second primary tumor may benefit more from pulmonary resection. PMID- 11216768 TI - Blunt chest trauma with deep pulmonary laceration. AB - BACKGROUND: Deep pulmonary laceration (DPL) is rare and its survival rate is low. The present study focused on the prognostic factors of DPL. METHODS: The present study concerned 17 DPL patients treated in Tokai University Hospital between 1988 and 1998. The prognostic factors of DPL were compared with systolic blood pressure (SBP), PaO2, and the volume of intrathoracic blood loss. Characteristic findings of initial chest roentgenograms of DPL were investigated. RESULTS: Eleven patients were saved and 6 patients died. An SBP of less than 80 mm Hg on arrival at the hospital and a blood loss of more than 1,000 mL through the chest tube within 2 hours after arrival were poor prognostic factors. Hypoxemia on arrival was not a poor prognostic factor. Chest roentgenograms showed macular infiltrative shadow with moderate lung collapse and deviation of the mediastinal shadow toward the unaffected side. Selective bronchial occlusion with a Univent prevented suffocation by intrabronchial blood. CONCLUSIONS: Two poor prognostic factors of DPL are SBP less than 80 mm Hg on arrival and blood loss of more than 1,000 mL through the chest tube within 2 hours after arrival. PMID- 11216769 TI - A comparative study of buttressed versus nonbuttressed staple line in pulmonary resections. AB - BACKGROUND: Prolonged air leak is the major limiting factor in early hospital discharge following pulmonary resection. The purpose of this study was to determine whether the use of bovine pericardial strips as a buttress along the lung staple line would decrease air leaks and hospital stay after lobectomy and segmentectomy. METHODS: This was a multicenter trial consisting of 80 patients undergoing pulmonary resection, randomly assigned to the control group (40 patients) or treatment group (40 patients). The treatment group had reinforcement with bovine pericardium. RESULTS: No statistical differences were noted in the mean intensive care unit length of stay (p = 0.9), number of days with a chest tube (p = 0.6), or total length of stay (p = 0.24). Increased air leak duration was associated with assignment to the control group (r = 0.27, p = 0.02). The mean duration of air leak was 2 days and the mean time to chest tube removal was 5.9 days in patients with a buttressed staple line compared to 3 days and 6.3 days, respectively, for patients with nonbuttressed staple lines. CONCLUSIONS: Within the data of this study, no statistical differences were noted between buttressed and nonbuttressed patients. However, the trend toward shortened air leak time and tube removal time was apparent in the buttressed group. With greater number of patients studied, it is likely that the cost of bovine pericardium would be justified by shorter air leak duration and hospitalization. PMID- 11216770 TI - Variables predicting adverse outcome in patients with deep sternal wound infection. AB - BACKGROUND: Mortality after deep sternal wound infection (DSWI) ranges between 5% and 47%. Variables predicting hospital mortality and prolonged hospital stay are still to be assessed. METHODS: Among 13,420 patients who underwent cardiac surgery in our institution between 1979 and 1999, DSWI developed in 112 cases (0.8%). Multiple variables were recorded prospectively and analyzed retrospectively as predictors of hospital death and prolonged (>30 days) hospital stay. The analyzed variables were divided into three groups: (1) related to the patient, including demographic variables and preoperative conditions; (2) related to cardiac operation; and (3) related to infection. Predictive variables were assessed by univariate and multivariate logistic regression analysis. RESULTS: Hospital mortality was 16.9%. The hospital stay of the 93 discharged patients ranged between 16 and 180 days (mean 31.3 +/- 15.2). Length of cardiac operation, length of stay in intensive care unit, interval between symptoms of DSWI and wound debridement were found to be the most significant predictors of bad outcome following DSWI. CONCLUSIONS: In our study demographic variables and preoperative conditions did not affect the prognosis of DSWI. Lower mortality rate and shorter hospital stay could be achieved with earlier and aggressive treatment of DSWI. PMID- 11216771 TI - Emergency operation for acute type A aortic dissection: neurologic complications and early mortality. AB - BACKGROUND: Acute type A aortic dissection is a surgical emergency still associated with high postoperative complications. The aim of this study was to investigate factors for hospital mortality and neurologic deficit in patients undergoing emergency operation for acute type A aortic dissection. METHODS: Eighty-five consecutive patients (age range, 20 to 82 years) operated on for acute type A aortic dissection over a 6-year period were evaluated. Univariate and stepwise multiple logistic regression analyses were conducted among 32 perioperative variables. RESULTS: All patients underwent surgical procedures under deep hypothermic circulatory arrest. Antegrade or retrograde cerebral perfusion was used in 23 patients (27.1%) and 18 patients (21.2%), respectively. Forty-three patients underwent arch/hemiarch replacement and the ascending aorta was replaced in 42 patients. Overall mortality rate was 25.9% (22 of 85 patients). Multiple logistic regression analysis showed that lack of cerebral perfusion (p = 0.021) and postoperative renal failure (p = 0.006) were the best predictors for hospital death. Twenty-one patients (24.7%) experienced neurologic accidents. The risk factor for postoperative neurologic complication was lack of cerebral perfusion (p = 0.013). Hospital mortality was 13% (3 of 23 patients) and 16.7% (3 of 18 patients) in the antegrade and retrograde cerebral perfusion groups (p > 0.05) and neurologic deficit was 13% (3 of 23 patients) and 11.1% (2 of 18 patients), respectively (p > 0.05). CONCLUSIONS: Hospital mortality and neurologic complications in patients undergoing emergent operation for acute type A aortic dissection were reduced when cerebral perfusion was used with deep hypothermic circulatory arrest. PMID- 11216772 TI - Bronchial transsection and reanastomosis in pigs with and without bronchial arterial circulation. AB - BACKGROUND: The bronchial artery may be vital to the bronchi and lung parenchyma, but results of lung transplantation have raised doubts. This study was performed to examine the effect of bronchial arterial devascularization on bronchial morphology after bronchial transsection and reanastomosis. METHODS: In 6 pigs (study group), the left main bronchus was transsected, reanastomosed, and devascularized. Six control pigs had the same operation without devascularization. After 1 week, bronchial arterial angiography was performed, and specimens were examined with conventional histology and scanning electron microscopy. RESULTS: Histology showed significant changes (inflammation, edema, and fibrosis) in bronchi and lung parenchyma of the study group compared with the unoperated side (p = 0.028) and with the control group (p = 0.050). Scanning electron microscopy showed significant ciliary denudation in the study group's left bronchus compared with the unoperated side (p = 0.043) and with the control group (p = 0.0071). CONCLUSIONS: The loss of cilia of the bronchial epithelium and the occurrence of inflammation, edema, and fibrosis in bronchi and lung parenchyma 1 week postoperatively were significantly related to the absence of the bronchial arterial circulation. PMID- 11216773 TI - Duration of knowledge in general thoracic surgery. AB - BACKGROUND: Medical knowledge changes rapidly, so current medical education approaches emphasize the development of life-long learning skills ("teaching the learner to learn") as opposed to the simple acquisition of contemporary medical knowledge. Because there are no data on the rapidity of change of general thoracic surgical knowledge, we do not know whether this trend in medical education is appropriate for thoracic surgical trainees. We undertook a study to assess the duration of knowledge in general thoracic surgery. METHODS: The first general thoracic surgery article from each issue of The Annals of Thoracic Surgery between 1965 and 1997 was abstracted into a summary statement. A form, made up of 360 summary statements in random order, was assessed by 6 general thoracic surgeons. They assessed statement validity on a 5-point scale (1 = statement false; 5 = statement true). Average statement validity scores for 30 time intervals were calculated. The relationship between time of publication and statement validity was analyzed. RESULTS: Average validity scores ranged from 2.24 (represents 1965 to 1966) to 4.32 (represents 1969 to 1970). Validity scores increased with time (y = 3.46 + 0.017x, where y is validity score and x is time), and this was significant (r = 0.40; p = 0.027). However, the absolute change in average validity scores over the 33-year study period was only 0.52 or 13.1% of the "modern" era scores. CONCLUSIONS: The assumption that medical knowledge changes quickly may not be true in general thoracic surgery. Although life-long learning skills are important, general thoracic surgery training programs should continue to emphasize fundamental knowledge in the specialty. PMID- 11216774 TI - Cocaine abuse and coronary artery dissection. AB - A 33-year-old man with a history of recent cocaine use presented with dissection of the left main coronary artery extending distally to involve the left anterior descending (LAD) and circumflex arteries. He required emergency four-vessel aortocoronary bypass, which was uncomplicated. PMID- 11216775 TI - Vineberg graft: flow reserve of bilateral implantation after 27 years. AB - We report a patient who underwent bilateral internal thoracic artery implantation into the myocardium known as a Vineberg procedure 27 years ago. Coronary angiography and Doppler echocardiography revealed patent grafts with total occlusion of all native coronary arteries. We measured flow velocities at rest and under stress conditions with noninvasive ultrasonic Doppler echocardiography. The flow patterns in both grafts were biphasic as in native coronary arteries. Under stress conditions no increase in flow was detectable as a marker of end stage coronary artery disease with refractory angina pectoris. PMID- 11216776 TI - Left ventricular-right atrial fistula complicating redo mitral valve replacement. AB - We describe the case of a 58-year-old female patient who underwent redo mitral valve replacement and remained in heart failure. The diagnosis of a left ventricular-right atrial fistula was made. The fistula was closed surgically with a patch of autologous pericardium. The patient improved immediately after the operation and has been asymptomatic since. PMID- 11216777 TI - Surgical treatment of a hemangioma of the mitral valve. AB - Hemangioma of the heart is a rare lesion, representing 5% to 10% of benign cardiac tumors. Hemangioma of the mitral valve has been reported previously in one autopsy case report. We describe the excision and repair of a hemangioma of the mitral valve in a 33-year-old African-American woman. PMID- 11216778 TI - Thoracoabdominal aortic repair in a 190-kg patient: optimized perfusion with two oxygenators. AB - A 190-kg patient was referred because of an acute type B aortic dissection. Conservative management was initially performed but the 34-year-old patient was shown to have an increasing aortic diameter 2 months later and was scheduled for elective repair of the thoracoabdominal aorta. To anticipate potential difficulties with perfusion and oxygenation the cardiopulmonary bypass circuit was constructed with two parallel oxygenators, which allowed an adequate oxygen supply through all phases of the intervention and accelerated the estimated rewarming time. PMID- 11216779 TI - Pyodera gangrenosum after aortic valve replacement. AB - A 68-year-old male patient developed pyoderma gangrenosum after elective aortic valve replacement. Treatment with steroids and clofazimine was initiated, which resulted in rapid cessation of the necrotic process. Due to thoracic instability, stabilization of the sternum was performed followed by surgical debridement and atraumatic wound closure. Postoperatively, immunosuppression with cyclosporine A was added; the patient recovered completely. Pyoderma gangrenosum is a potential life-threatening complication that must be considered in patients with severely impaired wound healing after cardiac operation. PMID- 11216781 TI - Stunned myocardium after off-pump coronary artery bypass grafting. AB - Off-pump coronary artery bypass grafting is increasingly performed. Because these procedures are associated with temporary myocardial ischemia, there is a risk of ischemia-related complications. We report two cases of myocardial stunning after off-pump coronary artery bypass grafting using the Octopus tissue stabilizer. On the basis of our experiences, means to prevent stunning are discussed. PMID- 11216782 TI - Pulmonary atresia, ventricular septal defect, and coronary-pulmonary artery fistula. AB - We report 2 patients with pulmonary atresia, ventricular septal defect, and coronary-pulmonary fistula. The fistula originated from the left anterior descending artery in 1 patient, and from the right coronary artery in the other. Both patients survived staged correction in which right ventricular outflow was reconstructed with autologous fistula tissue. One patient with pulmonary hypertension suddenly died 9 months after surgery. Twenty-four patients with pulmonary atresia, ventricular septal defect, and coronary-pulmonary fistula have been reported previously. PMID- 11216780 TI - Cardiac operation for a patient with autoimmune hemolytic anemia with warm reactive antibodies. AB - We present a case of a patient with autoimmune hemolytic anemia with warm reactive antibodies who underwent successful coronary artery bypass grafting. We discuss some of the important problematic issues related to perioperative management. PMID- 11216783 TI - Anomalous right coronary artery originating from the left main coronary artery. AB - A 54-year-old man with no cardiac history presented with exertional angina. Cardiac catheterization revealed an anomalous right coronary artery originating from the left main coronary artery with external compression during its course between the aorta and the pulmonary artery. He was successfully managed with surgical reimplantation of the right coronary artery into the aorta. PMID- 11216784 TI - Double orifice right atrioventricular valve in atrioventricular septal defect: morphology and extension of the concept of fusion of leaflets. AB - A rare observation of a double orifice right atrioventricular valve in a partial form of atrioventricular septal defect is reported. The concept of leaflet fusion along part of their anticipated zones of apposition is used to explain the formation of this anomaly. We show that this concept can account for the different morphologic presentations of atrioventricular septal defect. PMID- 11216785 TI - Absorbable pulmonary artery banding in tricuspid atresia. AB - A child with tricuspid atresia, concordant ventriculoarterial connections, large ventricular septal defect, and elevated pulmonary artery pressure underwent pulmonary artery banding with a polydioxanone ribbon. This procedure was successful in this patient as the ventricular septal defect became restrictive while the banding was fully absorbed after 5 months. This technique could be included in the panel of surgical strategies for patients with single ventricle physiology and potential but insufficient subpulmonary stenosis in early infancy. PMID- 11216786 TI - Simplified retrograde systemic perfusion for removal of air from the aorta in an infant. AB - Total circulatory arrest with full venous drainage can result in air entering the arterial system through several possible sites such as the aortic cannulation site or collateral vessels. Air present in the arterial system during total circulatory arrest imposes a special problem. We describe a simple technique of short-term retrograde systemic perfusion to remove air from the arterial system before restarting systemic arterial perfusion after total circulatory arrest. PMID- 11216787 TI - Nitric oxide usage after posttraumatic pneumonectomy. AB - Pneumonectomy is rarely required in the surgical management of thoracic traumatic injuries with high mortality rates. Right heart failure due to elevated pulmonary artery pressure and the adult respiratory distress syndrome have been leading causes of mortality reported after posttraumatic pneumonectomy. The beneficial effect of inhaled nitric oxide has been shown in pulmonary hypertension and in adult respiratory distress syndrome. We report the use of inhaled nitric oxide in the perioperative management of a patient undergoing emergent pneumonectomy. PMID- 11216788 TI - Successful treatment of mucoepidermoid carcinoma of the carina. AB - We successfully treated a 33-year-old man with mucoepidermoid carcinoma at the carina. Through preoperative spiral computed tomography with multiplanar and three-dimensional reconstructions, the lesion extended along the right main bronchus across the orifice of the right upper lobe. He underwent a carinal resection plus right upper lobectomy and reconstruction of the carina. He shows neither anastomotic complication nor recurrence of disease 1 year after surgery. Spiral computed tomography was used to evaluate the preoperative and postoperative state of the central airway. PMID- 11216789 TI - Removal of an intrathoracic migrated fixation pin by thoracoscopy. AB - Migration of orthopedic fixation pins into the thoracic cavity can result in perforation of pulmonary vasculature, aorta, bronchus, atrium, or ventricle. Prompt diagnosis and treatment is tantamount in preventing devastating consequences. A patient who had fixation of a right humeral fracture weeks later had intrathoracic migration of a fixation pin, found by routine postoperative radiographic examination. Because the patient was asymptomatic, we removed the pin with a thoracoscopic operation. The foreign body was retrieved successfully without intraoperative or postoperative complication. PMID- 11216790 TI - Ruptured thymoma causing mediastinal hemorrhage resected via partial sternotomy. AB - A case of a ruptured thymoma causing mediastinal hemorrhage and hemothorax that was electively resected by a partial sternotomy approach is presented. This case and others previously reported illustrate that a sudden onset of dyspnea and chest pain accompanied by acute mediastinal widening on chest roentgenogram in a previously healthy patient should suggest the diagnosis of a ruptured thymoma. An upper part sternotomy approach may be as safe and effective as a less invasive surgical procedure in resection of noninvasive thymomas, even if dense tumor adhesion exists. PMID- 11216792 TI - Intramural aortic hematoma syndrome. PMID- 11216791 TI - Hydatid disease of rib. AB - Osseous hydatidosis, especially when located in the rib, is a very rare disease. In 1978, only 39 costal echinococcosis cases were published. The course of the disease is generally slow and laboratory tests are frequently negative. Diagnosis is generally made through the combined assessment of clinical, radiologic, and laboratory data. Living in a rural area is an important risk factor for the disease. The gold standard for therapy is radical removal of the involved ribs or chest wall. We present the case of a 63-year-old herdsman with costal echinococcosis and a review of the literature. PMID- 11216793 TI - A new operation for ventricular septal defect with aortic incompetence. AB - Two boys, 10 years of age, with ventricular septal defect and severe aortic insufficiency were treated using a new method. An autograft of anterior pulmonary artery wall and the adjacent leaflet and subpulmonary muscle was excised. The excised pulmonary artery segment was used to replace the prolapsed right coronary cusp, and the autograft muscle was used to close the ventricular septal defect. The right ventricular outflow tract and pulmonary valve were repaired using an autologous pericardial patch with an autologous single cusp. The results in both cases were satisfactory. PMID- 11216794 TI - Transaortic approach for the Alfieri stitch. AB - The management of associated mitral regurgitation in patients undergoing cardiac surgery is controversial. A simple, reliable, and fast repair is advantageous, especially in critically ill patients. We describe a simple method of transaortic edge-to-edge repair in patients with associated mitral regurgitation undergoing aortic valve surgery. PMID- 11216795 TI - Triangular resection of the anterior leaflet for repair of the mitral valve. AB - Isolated anterior mitral leaflet prolapse, unlike posterior prolapse, is a difficult lesion to repair and may become a demanding surgical procedure. We report our experience with a technique of a triangular resection of the anterior leaflet to repair isolated segmental anterior leaflet prolapse in 18 patients. This technique simplifies the repair procedure and is a safe and rapid procedure which allows excellent results. PMID- 11216796 TI - Redo left anterior descending artery grafting via left anterior small thoracotomy: an alternative approach. AB - Reoperative left anterior descending artery (LAD) revascularization can be performed through a left anterior small thoracotomy (LAST approach) in patients requiring isolated LAD revascularization. If the left internal mammary artery has been previously used, however, the operation is generally performed either through a median sternotomy or through a full posterolateral thoracotomy for the necessity of connecting the vein graft to the ascending aorta or to the descending thoracic aorta, thus losing the advantages of a minimally invasive approach. In the case reported herein, we describe a technique in which reoperative revascularization of the LAD is accomplished through the LAST approach, using the stump of the left internal mammary artery as the inflow site of a saphenous vein coronary graft to the LAD. PMID- 11216797 TI - Giant bronchial carcinoid tumors: a multidisciplinary approach. AB - BACKGROUND: Bronchial carcinoid tumors account for approximately 2% of all lung tumors. Although they were considered benign lesions, they are now categorized malignant, occasionally with poor prognosis. The clinical symptoms can be highly variable and are often present for many years before diagnosis. Whereas some carcinoids are entirely asymptomatic, others are accompanied by carcinoid or paraneoplastic syndromes. METHODS: We describe the multidisciplinary management of a 34-year-old female patient with a massive actively secreting bronchial carcinoid tumor of the right lung. Furthermore, we provide a review of the literature regarding the operative treatment and the perioperative management of pulmonary carcinoid tumors with respect to surgical, anesthetic, radiologic, and pathologic considerations. RESULTS: In the reported case, the first symptoms were chronic watery diarrhea, skin flushing, progressive shortness of breath, and increasing right shoulder pain. When the patient initially presented at our institution, the tumor had already reached an enormous size and it involved the right and left atrium as well as the atrial septum. Using an evidence-based, multidisciplinary approach the patient was treated successfully with extended surgical resection. CONCLUSIONS: Carcinoid tumors are potentially curable even if they reach a significant size and thus an aggressive strategy is warranted. The management of such cases requires careful investigation, planning, and treatment with collaborative expertise provided by a multidisciplinary team. We demonstrated that this approach can lead to a favorable outcome in what first appeared to be a formidable and unresectable tumor. PMID- 11216798 TI - Choice of venous cannulation for bypass during repair of traumatic rupture of the aorta. AB - BACKGROUND: Choices for venous cannulation for left heart bypass, to assist repair of traumatic rupture of the thoracic aorta, are between the left atrial appendage and pulmonary veins. METHODS: A retrospective chart review was performed of patients who underwent operative repair of ruptured aorta. RESULTS: Over a 15-year period between March 1985 and February 2000, 133 patients were admitted to a level I trauma center with aortic rupture. Of the 50 procedures performed with left heart bypass, the left atrial appendage was cannulated in 19 and pulmonary veins in 31 (four superior, 27 inferior). Complications occurred in 7 of the 19 patients who underwent venous cannulation via the atrial appendage (two ventricular fibrillation, three atrial fibrillation, one pericardial effusion leading to tamponade, and one phrenic nerve injury). Complications occurred in 2 patients who underwent cannulation via pulmonary vein (one atrial fibrillation, one pericardial effusion requiring tapping) (p = 0.02). CONCLUSIONS: Cannulation via the pulmonary veins is associated with a decrease in complication rates compared with cannulation of the atrial appendage. PMID- 11216799 TI - Severe respiratory failure. PMID- 11216800 TI - Reversibility of anorexigenic valvulopathy. PMID- 11216801 TI - Epiaortic ultrasound, Y graft, and postoperative neuropsychological dysfunction. PMID- 11216802 TI - Resident training in off-pump CABG. PMID- 11216803 TI - Innominate artery cannulation in patients with severe porcelain aorta. PMID- 11216804 TI - Stroke after coronary artery bypass grafting: are we forgetting atrial fibrillation? PMID- 11216805 TI - Advantages of pressure-controlled intermittent coronary sinus occlusion over left ventricle-powered coronary sinus retroperfusion. PMID- 11216806 TI - Minimally invasive resection of mediastinal parathyroid adenomas. PMID- 11216807 TI - Long-term preservation of isolated heart. PMID- 11216809 TI - Surgical outcome of double-outlet right ventricle with subpulmonary VSD. AB - BACKGROUND: Optimal management of double-outlet right ventricle with subpulmonary ventricular septal defect remains controversial. We reviewed our 7-year experience with patients who had this anatomic configuration. METHODS: Between January 1992 and January 1999, 20 patients underwent an arterial switch operation (ASO group), and 12 underwent a bidirectional Glenn procedure followed by a modified Fontan in 10 (Glenn/Fontan). Mean follow-up was 23 +/- 18 months. RESULTS: An initial palliative operation was done in 19 patients (9 in the ASO group, 10 in the Glenn/Fontan group). There were no deaths in the Glenn/Fontan group. Four patients in the ASO group died within 33 days postoperatively. Two of them had a single coronary artery, 1 had a straddling mitral valve, 1 had a hypoplastic aortic arch, and 1 had multiple ventricular septal defects. Three patients had reoperation for subaortic stenosis (n = 2) or pulmonary stenosis (n = 1) after the ASO. Four patients (3 in the ASO group, 1 in the Glenn/Fontan) required a pacemaker for postoperative complete atrioventricular block. Actuarial survival at 5 years for the entire group was 87% (70% confidence interval, 81% to 93%). CONCLUSIONS: The ASO remains our preferred treatment for infants with double-outlet right ventricle and subpulmonary ventricular septal defect. However, associated anatomic defects are important risk factors. PMID- 11216808 TI - Prospective randomized trial of azathioprine in cryopreserved valved allografts in children. AB - BACKGROUND: The purpose of this study was to prospectively assess the effects of azathioprine on the humoral immune response to HLA alloantigens and allograft function in children receiving cryopreserved valved allografts. METHODS: We randomized 13 children to receive azathioprine or not to receive azathioprine (controls) after receiving a cryopreserved valved allograft. Azathioprine patients received intraoperatively 4 mg/kg of azathioprine and 2.0 +/- 0.5 mg/kg once daily for 3 months after operation. Panel reactive antibodies against HLA class I and class II alloantigens were measured before, 1 month, and 3 months after operation. RESULTS: Panel reactive antibodies were not significantly different between the azathioprine and control groups before (0.0% +/- 0% versus 1.6% +/- 1%), 1 month (59% +/- 17% versus 71% +/- 12%), or 3 months (84% +/- 15% versus 96% +/- 1.3%) after operation. There were no differences in degree of allograft valve stenosis between azathioprine (31.5 +/- 26 mm Hg, 13.4 +/- 7 months postoperatively) and control groups (25.4 +/- 11 mm Hg, 17.2 +/- 10 months postoperatively) or allograft valve insufficiency. CONCLUSIONS: Azathioprine does not significantly decrease the immune response to HLA alloantigens or affect the function of cryopreserved valved allografts used in children to repair congenital heart defects. PMID- 11216810 TI - Cryopreserved homografts in the pulmonary position: determinants of durability. AB - BACKGROUND: The cryopreserved homograft has emerged as the pulmonary conduit of choice for the repair of many congenital heart defects. It is also used for pulmonary valve replacement in the Ross procedure. Because of a wide range of patient ages and diagnoses, the risk of homograft failure may vary. METHODS: We reviewed 185 consecutive pulmonary position implants performed between September 1985 and January 1999. We examined three age groups: patients less than 1 year of age (n = 53), patients 1 to 10 years of age (n = 46), and patients more than 10 years of age (n = 86). RESULTS: Five-year Kaplan-Meier homograft survival was 25%, 61%, and 81% for the groups, respectively (p < 0.02). Smaller homograft size, younger patient age, and truncus arteriosus were risk factors for homograft failure in univariate analysis (p < 0.05). Smaller homograft size was the only predictor for homograft failure in multivariate analysis (p < 0.001). Twenty of 99 implants in patients less than 10 years old underwent transcatheter intervention. The 3-year Kaplan-Meier implant survival of this group (79%) was not different from those who did not undergo intervention (77%, p = 0.84). Survival of aortic and pulmonary homografts in patients less than 10 years of age was not different (p = 0.35). Ross procedure implants appear to have optimal survival (94%) at 5 years. Non-Ross implants in patients more than 10 years of age have 76% 5-year Kaplan-Meier survival, which is not different from Ross patients (p = 0.33). CONCLUSIONS: Small homografts have limited durability. Aortic homografts perform as well as pulmonary homografts in young patients. Once patients receive an "adult-size" homograft, at approximately 10 years of age, risk for implant failure approximates that of patients undergoing the Ross procedure. Transcatheter interventions, when indicated, may prolong homograft life. PMID- 11216811 TI - Unexpected death after reconstructive surgery for hypoplastic left heart syndrome. AB - BACKGROUND: Although operative mortality for reconstructive surgery for hypoplastic left heart syndrome continues to improve, nonoperative mortality, especially in the first year of life, remains relatively high. A number of patients who are thought to be clinically well at hospital discharge die unexpectedly. The goal of the present study was to determine the incidence of and risk factors for unexpected death in patients with hypoplastic left heart syndrome. METHODS: Retrospectively, we determined the incidence of unexpected death among 536 patients with hypoplastic left heart syndrome who were discharged to home after stage I surgical procedure. To identify potential risk factors, a nested case-control analysis was undertaken. RESULTS: Unexpected death occurred in 22 of 536 patients (4.1%) discharged to home after stage I surgical procedure. The median age at unexpected death was 79 days (range, 25 to 227 days). Seizures preceded cardiac arrest in 2 patients, and ventricular arrhythmias were documented in 3 additional patients during attempted resuscitation. Autopsy studies were performed in 12 patients and identified residual lesions that may have contributed to death in 2 patients. In multivariate analysis documented perioperative arrhythmia and earlier year of stage I surgical procedure were associated with an increased risk for unexpected death (p = 0.03 and p = 0.04, respectively). There were 4 additional patients who had unexpected death after subsequent cavopulmonary operation at a median age of 1.6 years (range, 0.9 to 3.8 years). CONCLUSIONS: Unexpected death occurred in more than 4% of patients with hypoplastic left heart syndrome who were discharged to home after stage I surgical procedure and was most common in the first several months of life. Factors that may contribute to unexpected death include residual lesions, arrhythmias, and neurologic events, although in the majority of cases the cause remains largely unknown. PMID- 11216812 TI - Pediatric cardiac retransplantation: intermediate-term results. AB - BACKGROUND: Cardiac retransplantation (re-CTx) in children is a controversial therapy, yet it remains the best treatment option to recipients with failing grafts. Our objective was to determine the incidence of re-CTx in a large pediatric population of recipients and evaluate the outcome of such therapy. METHODS: Between November 1985 and November 1999, 347 children underwent cardiac transplantation at the Loma Linda University Medical Center. Of these, 32 children were listed for re-CTx. Ten patients died while waiting, and 22 recipients underwent re-CTx. Median age at re-CTx was 7.1 years (range, 52 days to 20.1 years). RESULTS: Indications for re-CTx were allograft vasculopathy (n = 16), primary graft failure (n = 5), and acute rejection (n = 1). Two patients with primary graft failure underwent retransplantation within 24 hours of the first transplantation procedure while on extracorporeal membrane oxygenation support. Median time interval to re-CTx for the others was 7.2 years (range, 32 days to 9.4 years). Operative mortality for all cardiac re-CTx procedures was 13.6%. Causes of hospital mortality were pulmonary hypertension with graft failure (n = 2) and multiorgan failure (n = 1). Median hospital stay after re-CTx was 14.1 days (range, 6 to 45 days). There was one late death from severe rejection. Actuarial survival at 3 years for re-CTx was 81.9% +/- 8.9% compared with 77.3% +/- 2.6% for primary cardiac transplantation recipients (p = 0.70). CONCLUSIONS: Elective re-CTx can be performed with acceptable mortality. Although the number of patients undergoing retransplantation in this report is small and their long-term outcome is unknown, the intermediate-term survival after re-CTx is similar to that of children undergoing primary cardiac transplantation. PMID- 11216813 TI - Early experience with extracardiac Fontan operation. AB - BACKGROUND: The extracardiac Fontan (ECFO) operation has gained more widespread use over last decade. In this article we analyze our early experience with ECFO. METHODS: Thirty-three patients underwent ECFO at median age 4.1 years. Normothermic perfusion with the heart beating was used in 24 patients and cardioplegia in 7. Fenestration was not performed in the last 16 patients who underwent surgery without cardioplegia. RESULTS: The hospital mortality was 6% (2 patients). Necessity or duration of inotropic support, duration of mechanical ventilation, intensive care unit and hospital stay, and incidence of prolonged pleural effusions of patients operated on without cardioplegia were shorter and the rate of complications in these patients was lower than in patients who underwent cardioplegia. CONCLUSIONS: Our preliminary experience shows that ECFO can be performed in many patients with normothermic cardiopulmonary bypass and without cardioplegia and fenestration. Avoidance of cardioplegia seems to decrease postoperative morbidity. Incidence of early postoperative arrhythmias is low. Despite encouraging early results, longer follow-up is necessary to prove the real advantages of ECFO. PMID- 11216814 TI - Valvuloplasty with glutaraldehyde-treated autologous pericardium in patients with complex mitral valve pathology. AB - BACKGROUND: Severe mitral regurgitation associated with complex mitral valve disease often precludes successful surgical repair. The feasibility and the results of valvuloplasty with glutaraldehyde-treated autologous pericardium remain largely unknown. METHODS: The cases of 63 patients who underwent operation within an 11-year period were studied. A pretreated autologous pericardial patch was used for leaflet extension plasty, for paracommissural plasty, as a substitute for part of the leaflet, and for reimplantation of ruptured papillary muscles to eliminate severe mitral regurgitation. Patients with a severely calcified annulus after en bloc decalcification had straddling endoventricular pericardial patch annuloplasty for reconstruction of the affected atrioventricular groove. Chordal replacement with a strip of pericardium was chosen if no suitable chordae were available. Pericardium-reinforced suture annuloplasty was used in patients with acute endocarditis resistant to medical therapy. Associated valvuloplasty procedures with Carpentier techniques were also employed. RESULTS: There were no operative deaths in this series. At a mean follow-up of 61.1 months (range, 4 to 132 months), mitral regurgitation was absent or trivial in 92.1% of patients by echocardiography. Freedom from reoperation was 95.2% at 1 year and 5 years. Thromboembolic events have not been detected. Thirty percent of patients returned to sinus rhythm. Two patients required valve replacement. CONCLUSIONS: Our beneficial results indicate that glutaraldehyde-treated autologous pericardium is suitable for valvuloplasty. It provides durable and predictable repair of valves that might otherwise need to be replaced because of the complex mitral valve disease. The technique is reliable, allows further efficacious repair possibilities, and improves postoperative outcomes. Whether it can prevent late deterioration and calcification requires more investigation. PMID- 11216816 TI - Results of continual devaluation of cardiothoracic surgical codes by the HCFA between 1984 and 1999. AB - BACKGROUND: The devaluation of surgical procedural services by Medicare began in 1989 as a result of the federal government's adoption of the Resource Based Relative Value Scale, a method of redistribution of payments to physicians from surgical to primary care services. This method gave to the Health Care Financing Administration (HCFA) effective and complete control of Medicare payments to physicians for the first time. The resultant decrease in the nominal dollar value is well understood, but the effect of changes in inflation frequently is not calculated into the reported loss. METHODS: A method of determining the true extent of this devaluation using the nominal dollar decrease plus the effect of inflation was presented in 1995. RESULTS: Since then, repeated devaluation by the HCFA and other third parties plus continual inflation has further eroded the remuneration for cardiothoracic surgical services. Three different sets of data are used to determine the devaluation of five cardiothoracic operations. One set shows the change between 1988 and 1998; one the change between 1988 and 1999; and one the change between 1984 and 1999. CONCLUSIONS: Depending on the geographic location, it appears that the remuneration for pulmonary procedures between 1988 and 1999 decreased 35% to 60%. Similarly, depending on the years reviewed (between 1984 and 1999) and the geographic location, the fee for cardiac procedures decreased 46% to 69%. PMID- 11216815 TI - The CryoLife O'Brien stentless porcine aortic bioprosthesis: 5-year follow-up. AB - BACKGROUND: Mortality, morbidity, complication rates, and echo hemodynamic results using the Cryolife O'Brien stentless aortic bioprosthesis over a 5-year period are reported. METHODS: The stentless valve was implanted in 97 conscecutive patients, 54 male and 43 female, mean age 70.9 +/- 6.5 years. All patients underwent preoperative, discharge (early study), 6-month (intermediate study), and late (18.3 +/- 10.4 months) echocardiography. RESULTS: The actuarial 5-year survival rate was 93.9% +/- 3%. Aortic regurgitation was absent in 95.5%, mild in 3.4%, and moderate in 1.1%. Peak and mean systolic gradients were significantly lower at discharge (p < 0.001) and at the 6-month follow-up (p < 0.001) but did not significantly fall further at the late study (p = NS). The effective orifice area index at discharge (p < 0.001) and at 6 months (p < 0.001) differed significantly from preoperative values, but variations at late study were not significant (p = NS). Left ventricular mass index decreased early postoperatively (p < 0.001) and at 6-month assessment (p < 0.001) with a further significant reduction at late echocardiography (p = 0.04). CONCLUSIONS: The 5 year results of this stentless valve showed a low rate of valve-related complications with excellent hemodynamic performance in all valve sizes. PMID- 11216817 TI - In vivo hemodynamic, histologic, and antimineralization characteristics of the Mosaic bioprosthesis. AB - BACKGROUND: Performance of bioprosthetic valves is limited by tissue degeneration due to calcification with reduced performance and longevity. The Mosaic bioprosthetic valve (Medtronic Heart Valves, Inc, Minneapolis, MN) combines zero pressure fixation, antimineralization properties of alpha-amino oleic acid (AOA), and a proven stent design. We tested the hypothesis that AOA treatment of Mosaic valves improves hemodynamics, antimineralization properties, and survival in a chronic ovine model. METHODS: Mitral valves were implanted in juvenile sheep with Mosaic valves with AOA treatment (n = 8) or without AOA treatment (non-AOA, n = 8), or Hancock I (HAN, n = 4) tissue valves, and explanted at 20 postoperative weeks. RESULTS: Survival was equivalent in AOA and non-AOA (140 +/- 0.4 and 129 +/- 30 days), but was significantly less in HAN (82 +/- 35). Leaflet calcium (microgCa/mg tissue) was less in AOA (9.6 +/- 13.9; p < 0.05 versus non-AOA and HAN) than non-AOA (96.3 +/- 63.8) and HAN (130.8 +/- 43.2). Explant valve orifice area (cm2) was significantly preserved in the AOA group compared with the non-AOA group (1.5 +/- 0.7 vs 0.8 +/- 0.3; p < 0.05 versus non-AOA and HAN). CONCLUSIONS: We conclude that AOA treatment of Mosaic valves reduces leaflet calcification and valve gradient in juvenile sheep, and that the Mosaic design and fixation features may offer survival advantages that must be confirmed in extended trials. PMID- 11216818 TI - Characterization of T cell receptor beta chains of accumulating T cells in chronic ongoing myocarditis demonstrated by heterotopic cardiac transplantation in mice. AB - Autoimmne mechanisms have been implicated in the pathogenesis of chronic ongoing mycarditis. An earlier study of murine chronic ongoing myocarditis reported that infiltrating T cells and macrophages were prominent in the normal donor heart, in a heterotopic cardiac transplantation model. It was demonstrated that myocarditis was transferred to a normal heart transplanted into a mouse with chronic myocarditis. The present study investigated an autoimmune link to the pathogenesis of chronic ongoing myocarditis by analyzing the T cell clonalities in the model. To characterize the accumulating T cells in the donor heart, the T cell receptor beta genes (TCRBG) were amplified by reverse transcriptase polymerase chain reaction (RT-PCR) from mRNA in the donor hearts and accumulating TCRBG clonotypes were contrasted with those from recipient hearts. Inbred 3-week old A/J mice were inoculated intraperitoneally with Coxsackievirus B3 (Nancy strain), 2 x 10(4) PFU, and housed for more than 60 days. Normal A/J mouse hearts were transplanted into the same strain of mice without myocarditis, as well as into the mice with chronic ongoing myocarditis. Both recipient and donor hearts were evaluated histologically 2 weeks after the transplantation. TCRBG were amplified by RT-PCR from mRNA of recipient and donor hearts and spleens. The specific accumulating TCRBG clonotypes were identified by their single strand conformation polymorphism. Multiple clonotypic accumulations occurred in the donor heart after cardiac transplantation. Distinct oligoclonal accumulation of TCR Vbeta1, 10, and 13 T cells was found in both recipient and donor hearts in 3 of 4 mice. Moreover, these clonotypes were not observed in spleen cells of the recipient mice. T specific cells expanding clonotypes of TCRBG are responsible for transferring myocarditis to the donor heart. An autoimmune response may, therefore, play a key role in the progression of chronic ongoing myocarditis. PMID- 11216819 TI - Quantitative analysis of termination of vagally induced canine atrial fibrillation by mutual information. AB - Atrial fibrillation (AF) is often described as a disorganized phenomenon, but many features that qualitatively suggest an underlying order have recently been reported. The present study aimed to disclose this underlying order of AF in a quantitative manner, using a new method of mutual information (MI), which is a measure for gauging the general correlation between 2 time series. Frequency analysis and the MI method were used to analyze 5 epicardial potentials on both atria during AF induced by vagal stimulation (Vs) in 15 dogs. Unipolar electrodes were placed on the right atrial appendage (Rap), the high right atrium (HRA), and the left atrial appendage (Lap). The other 2 electrodes were placed equidistantly between HRA and Rap (RA1-RA2). The power spectrum of AF had a discrete peak around 17Hz during Vs. After Vs was stopped, the discrete peak shifted from 17Hz to 7 Hz on all epicardial leads. Taking RA2 as a reference, MI was calculated between RA2 and each of the other electrodes. The MI values (0.066+/-0.005) were greater than 0.047 (the critical value for correlated data) even during Vs. The MI values increased significantly from the highly active process of AF during Vs to the less active one (0.126+/-0.006) before termination of AF. In addition, the MI values increased more at the electrodes close to RA2 (RA1 and Rap) than at those far from it (HRA and Lap). These findings suggest that multiple wavelets, which are not random, progressively organize into a few major waves toward the termination of AF; therefore, AF is not a random phenomenon in this model. PMID- 11216821 TI - Angiographically documented coronary steal phenomenon evoked by the intracoronary infusion of bradykinin. AB - While studying flow-dependent coronary dilation using a Doppler flow velocity guidewire, total occlusion of a stenosed segment of the left circumflex artery during the intracoronary infusion of bradykinin was angiographically documented. Total occlusion was not demonstrated during intracoronary infusion of bradykinin after angioplasty. This is angiographic confirmation of the coronary steal phenomenon that has been previously described in the field of stress scintigraphy. PMID- 11216820 TI - Effect of hypercholesterolemia on macrophage infiltration after balloon injury to rabbit iliac artery. AB - Both hypercholesterolemia and vascular injury have been reported to induce macrophage infiltration, but their combined effect and the mechanism by which hypercholesterolemia enhances the infiltration remain to be clarified in vivo. To evaluate the effect of hypercholesterolemia on macrophage infiltration after vascular injury, the iliac arteries of hypercholesterolemic (HC) and normocholesterolemic (NC) rabbits were examined 2h, 1 day, 3 days, 7 days, and 14 days after balloon injury using immunohistochemical staining for macrophages, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1. Nuclear factor kappa-B (NF-kappaB) activation was also evaluated in fresh frozen iliac arteries using the electrophoretic mobility shift assay method. The fundamental difference between HC and NC was the amount of macrophage infiltration seen in HC from 7 days after balloon injury. Two out of 4 HC iliac arteries on the 7th day, and 3 out of 4 HC iliac arteries on the 14th day were positively stained with ICAM-1 in regenerated endothelium and neointima, whereas there were no positively stained NC iliac arteries. Neither HC nor NC tissues showed positive staining with VCAM-1. NF-kappaB was activated in HC 7 and 14 days after balloon injury, but not in NC. In conclusion, in vivo hypercholesterolemia induces macrophage infiltration after balloon injury and it is mediated by increased NF-kappaB activation promoting ICAM-1 expression. PMID- 11216822 TI - Cardiac dysfunction because of secondary hemochromatosis caused by congenital non spherocytic hemolytic anemia. AB - Most patients diagnosed with secondary hemochromatosis have had repeated blood transfusions. Cardiac failure accounts for approximately one-third of the deaths associated with hemochromatosis. Liver dysfunction or hormonal disorders such as diabetes generally precede cardiac failure. A 23-year-old woman with hemochromatosis had, despite significant left ventricular dysfunction, liver function within the normal range on biochemical evaluation. She was treated for congestive heart failure and given desferoxamine intravenously. She did not have primary hemochromatosis, and had not received multiple blood transfusions or iron supplement. As a child the patient had been diagnosed with congenital non spherocytic hemolytic anemia not requiring transfusion; thus, this is a unique case of secondary hemochromatosis. PMID- 11216823 TI - Transient but marked ST elevation in precordial leads caused by ischemia of the isolated right ventricular branch. AB - The present case is a 64 year-old man in whom transient but marked ST elevation was confirmed in the contralateral precordial leads (V1-3) during percutaneous transluminal coronary angioplasty (PTCA) of the proximal right coronary artery, suggesting that the patient had anteroseptal ischemia. The ST elevation persisted even after the balloon was deflated, and no changes in the left coronary artery were detected. In addition, blood flow in the affected area of the right coronary artery was favorable and there was a transient delay only in the right ventricular branch. Once blood flow in the right ventricular branch improved, ST returned to baseline, and when the right ventricular branch was again occluded by the balloon, ST elevation occurred in a reproducible manner. Hence, the electrocardiographic changes in the precordial leads were caused by occlusion of the right ventricular branch. It is rare to observe ST elevation caused by isolated right ventricular branch ischemia. PMID- 11216824 TI - Biventricular hypertrophic cardiomyopathy with right ventricular outflow tract obstruction associated with Noonan syndrome in an adult. AB - This report describes an adult patient with Noonan syndrome accompanied by biventricular hypertrophic cardiomyopathy causing isolated right ventricular outflow tract obstruction. Biventricular hypertrophic cardiomyopathy causing right- and/or left-side outflow tract obstruction, as well as valvular pulmonary stenosis, is relatively common in infants with Noonan syndrome. However, this condition without a dysplastic pulmonary valve, or indeed any polyvalvular dysplasia, is rare in adults with Noonan syndrome. Treatment with a beta adrenergic receptor blocking agent improved the patient's symptoms. Because neither the etiologic and prognostic relationship nor the genetic linkage between hypertrophic cardiomyopathy associated with Noonan syndrome and non-syndromic hypertrophic cardiomyopathy is clearly defined, clinicopathological findings and further follow-up may provide important evidence for the pathogenesis of hypertrophic cardiomyopathy. PMID- 11216825 TI - Tumor necrosis factor receptor superfamily 12 may destabilize atherosclerotic plaques by inducing matrix metalloproteinases. AB - Immunohistochemical staining of human atherosclerotic plaques revealed expression of the tumor necrosis factor receptor superfamily (TNFRSF) 12 in regions rich in macrophage/foam cells. The role of TNFRSF12 in the functioning of monocytes in relation to atherogenesis was investigated by analysis of cellular events after stimulation of TNFRSF12 in a human macrophage-like cell line, THP-1. Activation of the THP-1 cells on plates coated with monoclonal antibody against TNFRSF12 induced the expression of matrix metalloproteinases (MMPs) -1, -9, and -13. Furthermore, the expression patterns of TNFRSF12 and the MMPs overlapped in atherosclerotic plaques. Signaling of TNFRSF12 may thus contribute to the induction of extracellular matrix degrading enzymes in macrophages. PMID- 11216826 TI - Relationship between terminal QRS distortion on the admission electrocardiogram and the time course of left ventricular wall motion in anterior wall acute myocardial infarction. AB - In order to clarify the time course of left ventricular (LV) wall motion in patients with anterior acute myocardial infarction (AMI) showing terminal QRS distortion on the admission electrocardiogram (ECG), the present study examined 106 patients with their first anterior AMI (< or =6 h) who underwent emergency coronary arteriography and cardiac cathetherization at 1 and 6 months after the infarction. The patients were classified into 2 groups according to the presence (group A, n=23) or absence (group B, n=83) of terminal QRS distortion (emergence of the J point at > or =50% of the R-wave amplitude in leads with QR configuration and/or absence of S waves in leads with RS configuration) on the admission ECG. Group A had a lower LV ejection fraction and more reduced regional wall motion (RWM) in the infarct region at both 1 and 6 months after AMI than group B. The degree of improvement in RWM between 1 and 6 months after AMI was less in group A than in group B (-0.1+/-0.5 vs 0.4+/-0.6 SD/chord, p<0.01). This study indicates that patients with anterior AMI showing terminal QRS distortion on the admission ECG have more severely depressed LV wall motion and less improvement in RWM in the infarct region in the healing stage, suggesting that this sign is an indicator of severe myocardial damage. PMID- 11216827 TI - Relationship between myocardial damage and C-reactive protein levels immediately after onset of acute myocardial infarction. AB - The present study investigated the relationship between myocardial damage and C reactive protein (CRP) levels, with no increase in creatine kinase (CK) activity, immediately after the onset of acute myocardial infarction (AMI) in 85 patients with their first reperfused anterior AMI without CK elevation on admission and no ischemic events during hospitalization. Patients were classified into those with low levels (<0.3 mg/dl) of CRP (Group L; n=67) and those with high levels (> or =0.3 mg/dl) of CRP (Group H; n=18). Group H had a higher proportion of patients with a history of preinfarction angina (89 vs 55%, p<0.01), especially unstable angina. SigmaST in leads V1-6 on admission ECG was lower in Group H than in Group L (14+/-7 vs 21+/-13 mm, p<0.05). Predischarge left ventriculography showed that the left ventricular global ejection fraction (55+/-11 vs 48+/-10%, p<0.01) and SD/chord at the left anterior descending artery lesion (-1.7+/-0.9 vs -2.3+/-0.9, p<0.01) were better in Group H. Multivariate analysis demonstrated that both CRP on admission (p=0.011) and preinfarction angina (p=0.002) were independently associated with better regional wall motion (SD/chord >-2.0) before discharge. These results suggest that the clinical situation of elevated CRP immediately after onset is associated with less myocardial damage and better left ventricular function in reperfused anterior AMI. PMID- 11216829 TI - Risk stratification for sudden cardiac death in dilated cardiomyopathy using microvolt-level T-wave alternans. AB - Predicting sudden cardiac death (SCD) in patients with dilated cardiomyopathy (DCM) is difficult, so the present study evaluated the efficacy of microvolt level T-wave alternans (TWA) and compared it with conventional parameters for prospective risk stratification of SCD in patients with DCM. Eighty-two patients with DCM (53+/-15 years old, 67M/15F) underwent assessment of TWA, left ventricular end-diastolic diameter (LVDd), left ventricular ejection fraction (LVEF), signal-averaged ECG, and analysis of 24-h Holter monitoring and QT dispersion (QTd). The endpoint of the study was defined as either SCD or documented sustained ventricular tachycardia/ventricular fibrillation (SVT/VF) during the follow-up period. During an average follow-up period of 24 months, 1 patient died suddenly and 9 patients had SVT/VF. Kaplan-Meier survival analysis showed that TWA, LVEF (< or =35%), nonsustained ventricular tachycardia, and QTd (>90ms) were significant univariate risk stratifiers (p<0.005, p<0.005, p<0.005, and p<0.05, respectively). Multivariate Cox regression analysis showed that TWA and the LVEF were statistically significant independent risk stratifiers (p<0.05 and p<0.01, respectively). A combination of TWA and LVEF identified high risk DCM patients (p<0.01); TWA for the electrical substrate and the LVEF for the hemodynamic function. PMID- 11216828 TI - Expression of matrix metalloproteinases in patients with acute myocardial infarction. AB - This study investigated the clinical significance of matrix metalloproteinases (MMPs) in acute myocardial infarction (AMI) and the involvement of peripheral blood mononuclear cells (PBMCs), which are a possible source of MMPs in AMI. Forty patients with AMI were recruited. Plasma and PBMCs were isolated from peripheral blood on days 1, 7, 14 and 21 after the onset of AMI. Levels of MMP-1 and MMP-2 were measured by enzyme-linked immunosorbent assay. The MMP-1 level in the culture medium of PBMCs after incubation for 24h was designated as 'PBMC-MMP 1 level.' Plasma MMP-1 did not significantly change during the course of AMI, but the plasma MMP-2 levels increased gradually after the onset of AMI with maximum elevation on day 21 after onset. Plasma MMP-2 activity also became significantly elevated during the course of AMI. PBMC-MMP-1 levels in the patients were significantly higher than those in control subjects over the course of AMI. Significant positive correlations were observed between maximum PBMC-MMP-1 levels and maximum plasma C-reactive protein levels (r=+0.55, p<0.01) and left ventricular end-diastolic volume index (r=+0.63, p<0.001). In conclusion, plasma MMP-2 levels and activity and MMP-1 production by PBMCs are increased in patients with AMI. Inflammation after AMI may enhance production of MMP-1 by PBMCs. These changes may play an important role in the ventricular remodeling that occurs after AMI by promoting the degradation of the extracellular matrix. PMID- 11216830 TI - Nitric oxide-mediated vasodilatation is decreased in forearm resistance vessels in patients with coronary spastic angina. AB - It has been reported that coronary endothelial dysfunction is associated with the pathogenesis of coronary spasm, and that endothelial nitric oxide (NO) mediated vasodilatation was decreased in coronary epicardial arteries in patients with coronary spastic angina (CSA). However, there are few reports about the endothelial function in peripheral resistance vessels of patients with CSA, so the present study investigated the role of NO in forearm resistance vessels in such patients. The responses of forearm blood flow to acetylcholine (ACh; 8-24 microg/min) and sodium nitroprusside (SNP; 0.4-1.2 microg/ml) infusions was examined using plethysmography, and subsequently the responses to ACh after an infusion of N(G)-monomethyl-L-arginine (L-NMMA; 4 micromol/min, for 5 min) in 17 patients with CSA and 17 age- and sex- matched controls. The vasodilator responses to ACh and SNP were comparable between the 2 groups (p=NS). L-NMMA significantly suppressed the vasodilator responses to ACh in controls (p<0.05), but there was no significant difference in the responses to ACh before and after infusion of L-NMMA in patients with CSA (p=NS). These results indicate that endothelial NO-mediated vasodilatation is decreased in the forearm resistance vessels of patients with CSA. PMID- 11216831 TI - Effects of a two-week, hospitalized phase II cardiac rehabilitation program on physical capacity, lipid profiles and psychological variables in patients with acute myocardial infarction. AB - A new 2-week hospitalized phase II cardiac rehabilitation program has been designed and the present study sought to clarify whether the physical and psychological status of patients with acute myocardial infarction (AMI) improved after participation in the program. Fifty-one patients with AMI were enrolled in the rehabilitation program, which consisted of exercise training, education and counselling, and another 34 patients with AMI who did not participate in the program served as the control group. The physical and psychological status of the patients was evaluated before, at 1-month after the program, and at 6- and 12 months follow-ups. The physical status was assessed by exercise tolerance and serum lipid profiles and the psychological status was assessed by the Spielberger State-Trait anxiety inventory questionnaire (STAI) and self-rating questionnaire for depression. Quality of life (QOL) was assessed using established and validated QOL scales. After participation in the program, the exercise tolerance, serum lipid profiles and STAI anxiety score of the patients were improved significantly and at the 6-month follow-up these parameters remained improved and regular physical activity was maintained. The QOL score also improved significantly. Even at the 12-month follow-up, lipid profiles remained improved and regular physical activity was maintained. The 2-week hospitalized phase II cardiac rehabilitation program improved the management of cardiac risk factors and psychological status in patients with myocardial infarction (MI). It provides beneficial effects on the patient's physical and psychological activities in the recovery phase and may also contribute to the secondary prevention of MI. PMID- 11216832 TI - Pulse infusion thrombolysis (PIT) for large intracoronary thrombus: preventive effect against the 'no flow' phenomenon in revascularization therapy for acute myocardial infarction. AB - Because large thrombus is a limitation for revascularization in acute myocardial infarction (AMI), the present study evaluated the effectiveness of pulse infusion thrombolysis (PIT) in patients with an AMI with a large (>15 mm) coronary thrombus, focusing on the occurrence of the 'no flow' phenomenon. The retrospective study compared patients treated before (1988-95; Group A, n=74) and after (1996-99; Group B, n=40) the use of PIT, using the following parameters: lesion success (<50% stenosis during 30-min observation), procedural success (lesion success plus TIMI grade 3 flow), procedural no flow (TIMI grade 0 flow during the procedure with 'back and forth movement' of contrast dye after lesion success), persistent no flow (consistent no flow without any flow improvement at the final visualization despite intensive treatment), reocclusion rate and in hospital death. Group B was significantly better than Group A in procedural success (90% vs 66%; p=0.005), procedural 'no flow' (51% vs 15%; p<0.001), and persistent 'no flow' (34% vs 10%; p<0.05). Subgroup comparison was performed among the following groups: Direct-BA group (n=44): treated with mechanical angioplasty alone; ICT-BA group (n=40): treated with prior intracoronary thrombolysis and angioplasty; and PIT-BA group (n=30): treated with PIT and angioplasty. There were no differences in thrombus length and lesion success among these 3 groups. Procedural success was best achieved in PIT-BA: 97% vs 52% for Direct-BA (p=0.003) and 68% for ICT-BA (p=0.009). Procedural 'no flow' was least in PIT-BA: 50% vs 3.3% for Direct-BA (p=0.003) and 25% vs 3.3% for ICT-BA (p=0.042). Persistent 'no flow' was less frequent in PIT-BA than Direct-BA: 32% vs 3.3% (p=0.009). However, the difference between ICT-BA and Direct-BA was insignificant: 13% vs 3.3% (p=0.53). There were no differences in reocclusion rate and in-hospital death among the 3 subgroups. And there were no differences between Direct-BA and ICT-BA in any parameters. PIT was effective in preventing 'no flow' in the mechanical revasculalization for AMI especially those cases with a large thrombus. PMID- 11216833 TI - Thallium-201 single photon emission computed tomography (SPECT) in patients with duchenne's progressive muscular dystrophy: a histopathologic correlation study. AB - The pathomorphologic mechanism responsible for abnormal perfusion imaging during thallium-201 myocardial single photon emission computed tomography (201Tl-SPECT) in patients with Duchenne's progressive muscular dystrophy (DMD) was investigated. Hearts from 7 patients with DMD were evaluated histopathologically at autopsy and the results correlated with findings on initial and delayed resting 201Tl-SPECT images. The location of segments with perfusion defects correlated with the histopathologically abnormal segments in the hearts. Both the extent and degree of myocardial fibrosis were severe, especially in the posterolateral segment of the left ventricle. Severe transmural fibrosis and severe fatty infiltration were common in segments with perfusion defects. In areas of redistribution, the degree of fibrosis appeared to be greater than in areas of normal perfusion; and intermuscular edema was prominent. Thus, the degree and extent of perfusion defects detected by 201Tl-SPECT were compatible with the histopathology. The presence of the redistribution phenomenon may indicate ongoing fibrosis. Initial and delayed resting 201Tl-SPECT images can predict the site and progress of myocardial degeneration in patients with DMD. PMID- 11216834 TI - Enhanced luciferin entry causes rapid wound-induced light emission in plants expressing high levels of luciferase. AB - In-vivo imaging of transgenic tobacco plants (Nicotiana tobacum L.) expressing firefly luciferase under the control of the Arabidopsis phenylalanine ammonialyase 1 (PAL1)-promoter showed that luciferase-catalyzed light emission began immediately after the substrate luciferin was sprayed onto the leaves and reached a plateau phase after approximately 60 min. This luminescence could easily be detected for up to 24 h after luciferin application although the light intensity declined continuously during this period. A strong and rapid increase in light emission was observed within the first minutes after wounding of luciferin-sprayed leaves. However, these data did not correlate with luciferase activity analysed by an in-vitro enzyme assay. In addition, Arabidopsis plants expressing luciferase under the control of the constitutive 35S-promoter showed similar wound-induced light emission. In experiments in which only parts of the leaves were sprayed with luciferin solutions, it was shown that increased uptake of luciferin at the wound site and its transport through vascular tissue were the main reasons for the rapid burst of light produced by preformed luciferase activity. These data demonstrate that there are barriers that restrict luciferin entry into adult plants, and that luciferin availability can be a limiting factor in non-invasive luciferase assays. PMID- 11216835 TI - Phloem-specific expression of the pumpkin fruit trypsin inhibitor. AB - Vascular exudates of Cucurbita maxima (Duch.) contain a group of highly conserved serine proteinase inhibitors collectively called Pumpkin Fruit Trypsin Inhibitors (PFTIs) that prevent proteolytic activity of trypsin or chymotrypsin. Polyclonal antibodies raised against PFTIs were used to immunolocalize these low-molecular weight proteins within the phloem tissue and to study their developmental expression. The inhibitors were translocated throughout the transport phloem and were present in vascular exudates collected from both source and sink tissues throughout the plant. During the early stages of vascular development, PFTIs accumulated specifically in sieve element-companion cell complexes of the phloem tissue. Transcripts were initially detected by reverse transcription-polymerase chain reaction in seedlings 1 d after germination and the protein detected 24 h later. Pumpkin fruit trypsin inhibitors were present in both cell types of differentiating and translocating sieve element-companion cell complexes. The inhibitors were detected in the phloem of the bicollateral vascular bundles, but the protein was most consistently localized within the cortical and bundle associated extrafascicular phloem. PMID- 11216836 TI - Tracking individual wheat microspores in vitro: identification of embryogenic microspores and body axis formation in the embryo. AB - The development of isolated, defined wheat microspores undergoing in vitro embryogenesis has been followed by cell tracking. Isolated wheat (Triticum aestivum L.). microspores were immobilized in Sea Plaque agarose supported by a polypropylene mesh at a low cell density and cultured in a hormone-free, maltose containing medium in the presence of ovaries serving as a conditioning factor. Embryogenesis was followed in microspores isolated from immature anthers of freshly cut tillers or from heat- and starvation-treated, excised anthers. Three types of microspore were identified on the basis of their cytological features at the start of culture. Type- microspores had a big central vacuole and a nucleus close to the microspore wall, usually opposite to the germ pore. This type was identical to the late microspore stage in anthers developing in vivo. Microspores with a fragmented vacuole and a peripheral cytoplasmic pocket containing the nucleus were defined as type 2. In type-3 microspores the nucleus was positioned in a cytoplasmic pocket in the centre of the microspore. Tracking revealed that, irrespective of origin, type-1 microspores first developed into type 2 and then into type-3 microspores. After a few more days, type-3 microspores absorbed their vacuoles and differentiated into cytoplasm-rich and starch-accumulating cells, which then divided to form multicellular structures. Apparently the three types of microspore represent stages in a continuous process and not, as previously assumed, distinct classes of responding and non-responding microspores. The first cell division of the embryogenic microspores was always symmetric. Cell tracking also revealed that the original microspore wall opened opposite to a region in the multicellular microspore which consisted of cells containing starch grains while the remaining cells were starch grain-free. The starch-containing cells were located close to the germ pore of the microspore. In more advanced embryos the broken microspore wall was detected at the root pole of the embryo. PMID- 11216837 TI - NADH-stimulated, cyanide-resistant superoxide production in maize coleoptiles analyzed with a tetrazolium-based assay. AB - Using the tetrazolium salt XTT (Na,3'-[(phe-nylamino)-carbonyl]-3,4-tetrazolium] bis(4-methoxy-6-nitro)benzenesulfonic acid hydrate) as a sensitive and physiologically compatible probe for the determination of superoxide (O2*-) production in vivo, we have shown that maize (Zea mays L.) coleoptiles possess the capacity of generating O2*- in the apoplastic space. Our results are in agreement with the notion that this activity is localized at the plasma membrane and can be attributed to an O2*--synthesizing enzyme with catalytic and kinetic properties similar to that of the NADPH oxidase of mammalian phagocytes, with the important exception that it utilizes NADH instead of NADPH as electron donor. When applied to the apoplastic space, NADH strongly increased the O2*--producing activity of coleoptiles. The maize NADH-dependent O2*--synthase activity could clearly be differentiated from peroxidase-mediated O2*--synthesizing activity by its insensitivity to cyanide and azide, as well as by its much higher affinity to O2. Formation of O2*-, and concomitantly appearing H2O2, was preferentially localized in the outer epidermis of the coleoptile. The physiological significance of O2*- and H2O2 production in relation to the growth-controlling function of the epidermal cell wall is discussed. PMID- 11216838 TI - Gravitropic microtubule reorientation can be uncoupled from growth. AB - The causal relationship between gravitropic growth responses and microtubule reorientation has been studied. Growth and microtubule reorientation have been uncoupled during the gravitropic response of maize (Zea mays L.) coleoptiles. Microtubule orientation and growth were measured under three different conditions: (i) a gravitropic stimulation where the growth response was allowed to be expressed (intact seedlings were displaced from the vertical position by 90 degrees), (ii) a gravitropic stimulation where the growth response was suppressed (coleoptiles were attached to microscope slides and kept in a horizontal position), (iii) suppression of growth in the absence of gravitropic stimulation (coleoptiles were attached to microscope slides and kept in a vertical position). It was found that (i) gravitropic stimulation can induce a microtubular reorientation from transverse to longitudinal in the upper (slower growing) flank of the coleoptile, and an inhibition of growth; (ii) the reorientation of microtubules precedes the inhibition of growth; (iii) the gravitropic response of microtubules is weaker, not elevated, when the inhibition of growth is artificially enhanced by attaching the coleoptiles to a slide; and (iv) artificial inhibition of growth in the absence of gravitropic stimulation cannot induce a microtubular response. Thus, the extent of microtubule reorientation is not correlated with the extent of growth inhibition. Moreover, these findings demonstrate that microtubules do not reorient passively after growth changes, but actively in response to gravitropic stimulation. PMID- 11216839 TI - Utilization of mutants to analyze the interaction between Arabidopsis thaliana and its naturally root-associated Pseudomonas. AB - A model system based on the Arabidopsis thaliana (L.) Heynh. Ws ecotype and its naturally colonizing Pseudomonas thivervalensis rhizobacteria was defined. Pseudomonas strains colonizing A. thaliana were found to modify the root architecture either in vivo or in vitro. A gnotobiotic system using bacteria labelled with green fluorescent protein revealed that P. thivervalensis exhibited a colonization profile similar to that of other rhizobacterial species. Mutants of A. thaliana affected in root hair development and possible hormone perception were used to analyze the plant genetic determinants of bacterial colonization. A screen for mutants insensitive to P. thivervalensis colonization yielded two mutants found to be auxin resistant. This further supports a proposed role for bacterial auxin in inducing morphological modifications of roots. This work paves the way for studying the interaction between plants and non-pathogenic rhizobacteria in a gnotobiotic system, derived from a natural association, where interactions between both partners can be genetically dissected. PMID- 11216840 TI - Brassinolide may control aquaporin activities in Arabidopsis thaliana. AB - It is usually assumed that aquaporins present in the cellular membranes could be an important route in the control of water flux in plants, but evidence for this hypothesis is scarce. In this paper, we report measurements of the osmotic permeability (P(os) of protoplasts isolated from hypocotyls of wild-type and mutant Arabidopsis thaliana (L.) Heynh. Mutants were affected in their growth and exhibited different sensitivities to the phytohormone, brassinolide. For the two mutants studied (cpd: constitutive photomorphogenesis and dwarfism; bril: brassinosteroid insensitive), hypocotyl length was correlated to P(os) for the protoplasts. Under experimental conditions where hypocotyl growth had ceased, restoration of root, hypocotyl and petiole growth by brassinolide was correlated with an increase in P(os) of the hypocotyl protoplasts. We consider that the increase in Pos of the hypocotyl cells was needed because these cells were part of the transcellular water pathway of the plant. This is the first time, to our knowledge, that brassinolide has been shown to be involved in the modification of the water-transport properties of cell membranes. Our results also emphasize the importance of aquaporins and the transcellular pathway in water transport under normal growth conditions. PMID- 11216841 TI - Characterisation of programmed cell death during aerenchyma formation induced by ethylene or hypoxia in roots of maize (Zea mays L.). AB - Aerenchyma is a tissue type characterised by prominent intercellular spaces which enhance flooding tolerance in some plant species by facilitating gas diffusion between roots and the aerial environment. Aerenchyma in maize roots forms by collapse and death of some of the cortical cells in a process that can be promoted by imposing oxygen shortage or by ethylene treatment. Maize roots grown hydroponically in 3% oxygen, 1 microl x l(-1) ethylene or 21% oxygen (control) were analysed by a combination of light and electron microscopy. Use of in-situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) suggested internucleosomal cleavage of DNA. However, chromatin condensation detectable by electron microscopy was preceded by cytoplasmic changes including plasma membrane invagination and the formation of vesicles, in contrast to mammalian apoptosis in which chromatin condensation is the first detectable event. Later, cellular condensation, condensation of chromatin and the presence of intact organelles surrounded by membrane resembling apoptotic bodies were observed. All these events were complete before cell wall degradation was apparent. Therefore, aerenchyma formation initiated by hypoxia or ethylene appears to be a form of programmed cell death that shows characteristics in part resembling both apoptosis and cytoplasmic cell death in animal cells. PMID- 11216842 TI - The production of an inducible antisense alternative oxidase (Aox1a) plant. AB - Plant mitochondria contain an alternative oxidase (AOX) acting as a terminal electron acceptor of the alternative pathway in the electron transport chain. Here we describe the production of inducible antisense Aox1a plants of Arabidopsis thaliana (L.) Heynh. and the procedures used to determine the resulting alternative pathway activity. The Arabidopsis Aox1a cDNA sequence was cloned behind a copper-inducible promoter system in the antisense orientation. Arabidopsis thaliana (Columbia) plants were transformed by in-planta vacuum infiltration with Agrobacterium containing the antisense construct. Whole-leaf ethanol production was used as a measure to investigate alternative pathway activity in the presence of antimycin A. After 24 h, leaves from the copper induced, antisense line F1.1 produced up to 8.8 times more ethanol (via aerobic fermentation) than the non-induced and wild-type leaves, indicating effective cytochrome pathway inhibition by antimycin A and a decreased alternative pathway activity in induced F1.1 leaves. Transgene expression studies also revealed no expression in non-induced leaves and up until 24 h post-induction. Copper-induced transgenic leaves were less susceptible to alternative pathway inhibition than non-induced transgenic leaves, as seen via tissue-slice respiratory studies, and mitochondrial respiration, using F1.1 cell cultures, also supported this. These results demonstrate the successful production of a transgenic line of Arabidopsis in which the alternative pathway activity can be genetically manipulated with an inducible antisense system. PMID- 11216843 TI - Characterization and localization of a wound-inducible type I serine carboxypeptidase from leaves of tomato plants (Lycopersicon esculentum Mill.). AB - During the course of characterization of the wound-response related proteins from tomato (Lycopersicon esculentum Mill.) leaves, a serine carboxypeptidase (EC 3.4.16.1) was identified. An increase in peptidase activity in response to wounding, and the isolation of a protein with carboxypeptidase (CP) activity from tomato leaves had been reported previously, but the mRNA coding for the enzyme was not identified. We now report the isolation of a tomato leaf type I serine-CP cDNA whose corresponding mRNA is induced by wounding, systemin and methyl jasmonate. The protein sequence deduced from the cDNA exhibits homology to tomato CP, and barley and rice type I CPs. Southern blot results indicated that the CP gene is probably a member of a small gene family. Tomato CP mRNA was detected within 3 h after wounding, or treatment with systemin or methyl jasmonate. Employing Western blot analysis, CP protein was shown to increase 12 h after the treatments. Using the tomato def1 mutant, we have demonstrated that a functional octadecanoid pathway is necessary for CP transcription in response to wounding. Carboxypeptidase protein was immunolocalized as protein aggregates within the central vacuoles of palisade mesophyll cells as well as in vascular parenchyma where it had previously been found. Double labeling using antibodies specific for CP and inhibitor II indicated that the two proteins are colocalized in the vacuolar aggregates. Tomato CP is a member of the "late wound-inducible genes" whose mRNAs increase 4-12 h following wounding, in contrast to several "early wound-inducible genes", whose mRNAs appear within 30 min. The data support a role for the enzyme in protein turnover that occurs systemically in leaf cells in response to wounding. PMID- 11216844 TI - Ultrastructure of minor-vein phloem and assimilate export in summer and winter leaves of the symplasmically loading evergreens Ajuga reptans L., Aucuba japonica Thunb., and Hedera helix L. AB - Minor-vein ultrastructure and sugar export were studied in mature summer and winter leaves of the three broadleaf-evergreen species Ajuga reptans var. artropurpurescens L., Aucuba japonica Thunb. and Hedera helix L. to assess temperature effects on phloem loading. Leaves of the perennial herb Ajuga exported substantial amounts of assimilates in form of raffinose-family oligosaccharides (RFOs). Its minor-vein companion cells represent typical intermediary cells (ICs), with numerous small vacuoles and abundant plasmodesmal connectivity to the bundle sheath. The woody plants Hedera and Aucuba translocated sucrose as the dominant sugar species, and only traces of RFOs. Their minor-vein phloem possessed a layer of highly vacuolated cells (VCs) intervening between mesophyll and sieve elements. Depending on their location and ontogeny, VCs were classified either as companion or parenchyma cells. Both cell types showed symplasmic continuity to the adjacent mesophyll tissue although at a lower plasmodesmal frequency compared to the Ajuga ICs. p Chloromercuribenzenesulfonic acid did not reduce leaf sugar export in any of the plants, indicating a symplasmic mode of phloem loading. Winter leaves did not show symptoms of frost injury, and the vacuolar pattern in ICs and VCs was equally prominent in both seasons. Starch accumulation as a result of reduced phloem loading was not observed to be triggered by low temperature. In contrast, high amounts of starch were found in mesophyll and bundle-sheath cells of summer leaves. Physiological data on season-dependent leaf exudation showed the maintenance of sugar export in cold-acclimated winter leaves. PMID- 11216845 TI - Beta-1, 3-glucanase and chitinase transgenes in hybrids show distinctive and independent patterns of posttranscriptional gene silencing. AB - Nicotiana sylvestris Speg. & Comes transformed with a tobacco class-I beta-1,3 glucanase (GLU I ) cDNA driven by CaMV 35S RNA expression signals exhibits posttranscriptional gene silencing (PTGS) which is triggered between the cotyledon and two-leaf stages of seedling development and is postmeiotically reset to the high-expressing state during seed development. The incidence of GLU I PTGS in sibling plants differed for the two different transformants tested and increased with the number of T-DNA loci. Comparison of host class-I and class-II beta-1,3-glucanase gene expression suggests that a similarity of 60-70% in the coding-region is required for PTGS of the homologous host genes. The GLU I transformants exhibited a spatial gradient in PTGS, in which expression of the silent phenotype gradually increased in successive leaves toward the bottom of the plant. In contrast, transformants carrying an unrelated tobacco class I chitinase (CHN I) cDNA in the same expression vector exhibited discontinuous patterns of PTGS with adjacent high-expressing and silent leaves. The GLU I- and CHN I-specific patterns were maintained in hybrids homozygous for both T-DNA's indicating that two different transgenes present in the same genome can exhibit independent and distinctive patterns of PTGS. This implies that the nature of the transgene rather than a general pre-pattern of competence for PTGS or propagation of the silent state are important for pattern determination. PMID- 11216846 TI - Fructose 2,6-bisphosphate activates pyrophosphate: fructose-6-phosphate 1 phosphotransferase and increases triose phosphate to hexose phosphate cycling in heterotrophic cells. AB - The aim of this work was to establish the influence of fructose 2,6-bisphosphate (Fru-2,6-P2) on non-photosynthetic carbohydrate metabolism in plants. Heterotrophic callus lines exhibiting elevated levels of Fru-2,6-P2 were generated from transgenic tobacco (Nicotiana tabacum L.) plants expressing a modified rat liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase. Lines containing increased amounts of Fru-2,6-P2 had lower levels of hexose phosphates and higher levels of 3-phosphoglycerate than the untransformed control cultures. There was also a greater redistribution of label into the C6 position of sucrose and fructose, following incubation with [1-13C]glucose, in the lines possessing the highest amounts of Fru-2,6-P2, indicating a greater re-synthesis of hexose phosphates from triose phosphates in these lines. Despite these changes, there were no marked differences between lines in the metabolism of 14C-substrates, the rate of oxygen uptake, carbohydrate accumulation or nucleotide pool sizes. These data provide direct evidence that physiologically relevant changes in the level of Fru-2,6-P2 can affect pyrophosphate: fructose-6-phosphate 1-phosphotransferase (PFP) activity in vivo, and are consistent with PFP operating in a net glycolytic direction in the heterotrophic culture. However, the results also show that activating PFP has little direct effect on heterotrophic carbohydrate metabolism beyond increasing the rate of cycling between hexose phosphates and triose phosphates. PMID- 11216847 TI - Cytosolic glutamine synthetase and not nitrate reductase from the green alga Chlamydomonas reinhardtii is phosphorylated and binds 14-3-3 proteins. AB - The nitrate reductase activity from Chlamydomonas reinhardtii was not altered when extracts were incubated with yeast 14-3-3 proteins in the presence of Mg ATP. However, the C. reinhardtii extracts contained 14-3-3 proteins capable of inhibiting the spinach nitrate reductase, raising the question of their physiological substrates. Two C. reinhardtii proteins of about 48 and 35 kDa were eluted from 14-3-3 affinity chromatography columns and bound to 14-3-3s in overlay assays. The 48-kDa protein corresponded to the cytosolic isoform of glutamine synthetase (GS1). The GSI was phosphorylated by a Ca2+-and calmodulin dependent protein kinase partially purified from the alga. However, neither phosphorylation nor 14-3-3 binding seemed to change GS catalytic activity. PMID- 11216848 TI - Expression and distribution of a vaculoar aquaporin in young and mature leaf tissues of Brassica napus in relation to water fluxes. AB - Recently, it has been shown that water fluxes across biological membranes occur not only through the lipid bilayer but also through specialized water-conducting proteins, the so called aquaporins. In the present study, we investigated in young and mature leaves of Brassica napus L. the expression and localization of a vacuolar aquaporin homologous to radish gamma-tonoplast intrinsic protein/vacuolar-membrane integral protein of 23 kDa (TIP/VM 23). In-situ hybridization showed that these tonoplast aquaporins are highly expressed not only in developing but also in mature leaves, which export photosynthates. No substantial differences could be observed between different tissues of young and mature leaves. However, independent of the developmental stage, an immunohistochemical approach revealed that the vacuolar membrane of bundle-sheath cells contained more protein cross-reacting with antibodies raised against radish gamma-TIP/VM 23 than the mesophyll cells. The lowest labeling was detected in phloem cells. We compared these results with the distribution of plasma-membrane aquaporins cross-reacting with antibodies detecting a domain conserved among members of the plasma-membrane intrinsic protein 1 (PIP1) subfamily. We observed the same picture as for the vacuolar aquaporins. Furthermore, a high density of gold particles labeling proteins of the PIP1 group could be observed in plasmalemmasomes of the vascular parenchyma. Our results indicate that gamma TIP/VM 23 and PIP1 homologous proteins show a similar expression pattern. Based on these results it is tempting to speculate that bundle-sheath cells play an important role in facilitating water fluxes between the apoplastic and symplastic compartments in close proximity to the vascular tissue. PMID- 11216849 TI - Functional characterisation of Nicotiana tabacum xyloglucan endotransglycosylase (NtXET-1): generation of transgenic tobacco plants and changes in cell wall xyloglucan. AB - To study the function of xyloglucan endotransglycosylase (XET) in vivo we isolated, a tomato (Lycopersicon esculentum Mill.) XET cDNA (GenBank AA824986) from the homologous tobacco (Nicotiana tabacum L.) clone named NtXET-1 (Accession no. D86730). The expression pattern revealed highest levels of NtXET-1 mRNA in organs highly enriched in vascular tissue. The levels of NtXET-1 mRNA decreased in midribs with increasing age of leaves. Increasing leaf age was correlated with an increase in the average molecular weight (MW) of xyloglucan (XG) and a decrease in the relative growth rates of leaves. Transgenic tobacco plants with reduced levels of XET activity were created to further study the biochemical consequences of reduced levels of NtXET-1 expression. In two independent lines, total XET activity could be reduced by 56% and 37%, respectively, in midribs of tobacco plants transformed with an antisense construct. The decreased activity led to an increase in the average MW of XG by at least 20%. These two lines of evidence argue for NtXET-1 being involved in the incorporation of small XG molecules into the cell wall by transglycosylation. Reducing the incorporation of small XG molecules will result in a shift towards a higher average MW. The observed reduction in NtXET-1 expression and increase in the MW of XG in older leaves might be associated with strengthening of cell walls by reduced turnover and hydrolysis of XG. PMID- 11216850 TI - Cinnamic acid is a precursor of benzoic acids in cell cultures of Hypericum androsaemum L. but not in cell cultures of Centaurium erythraea RAFN. AB - Benzoic acids are precursors of xanthone biosynthesis which has been studied in cell cultures of Hypericum androsaemum (Hypericaceae) and Centaurium erythraea (Gentianaceae). In both cell cultures, methyl jasmonate induces the intracellular accumulation of a new xanthone. Under these inductive conditions, feeding experiments were performed with [U-14C]L-phenylalanine, [7-14C]benzoic acid and [7-14C]3-hydroxybenzoic acid. All three precursors were efficiently incorporated into the elicited xanthone in H. androsaemum, whereas 3-hydroxybenzoic acid was the only precursor to be incorporated into xanthones in C. erythraea. In addition, an appreciable increase in phenylalanine ammonia-lyase activity occurred only in methyl-jasmonate-treated cell cultures of H. androsaemum. Benzoic acids thus appear to be formed by different pathways in the two cell cultures studied. In H. androsaemum, benzoic acid is derived from cinnamic acid by side-chain degradation. In C. erythraea 3-hydroxybenzoic acid appears to originate directly from the shikimate pathway. PMID- 11216851 TI - Specificity of the accumulation of mRNAs and proteins of the plasma membrane and tonoplast aquaporins in radish organs. AB - Plant aquaporins occur in multiple isoforms and are distributed in both plasma membrane and tonoplast. We cloned cDNAs for plasma-membrane aquaporins (PAQ1, 1b, 1c, 2, 2b, and 2c) of radish (Raphanus sativus L.). The amino acid sequences of the PAQs showed on average 63% sequence identity. Their sequences were 23% identical to those of tonoplast aquaporins (gamma- and delta-VM23). A comprehensive investigation of the aquaporin mRNAs, including VM23, in seedlings, plants, flowers and seeds of radish showed a marked accumulation of all the mRNAs in hypocotyls and growing taproots. In other organs, the mRNA level of each isoform varied according to the organ. In petals, stamens, pistils and sepals of flowers, the levels of PAQ1, 1b, 1c and gamma-VM23 mRNAs were high, and mRNAs of all aquaporins except for delta-VM23 were detected at high levels in pericarps. The protein levels of aquaporins on the basis of the membrane protein were determined by immunoblotting. Proteins PAQ1 and VM23 were detected in every organ except for the mature petiole. The PAQ2 protein level was especially high in green cotyledons and leaves, but was extremely low in seedling cotyledons and hypocotyls. Proteins PAQ1, PAQ2 and VM23 were highly accumulated in growing pericarps, but not in the immature seeds. These results indicate that the gene expression of the aquaporin isoforms was individually regulated in an organ- and tissue-specific manner, and that the amounts of aquaporin protein, especially PAQ2, are regulated in certain tissues at the translational level and by the rate of protein turnover. PMID- 11216852 TI - A short-term exposure of cucumber plants to rising atmospheric CO2 increases leaf carbohydrate content and enhances nitrate reductase expression and activity. AB - Nitrate reductase (NR; EC 1.6.6.1) is the first enzyme of the nitrate assimilatory pathway and is regulated transcriptionally and post-translationally by several metabolic and environmental signals. To investigate whether NR is controlled by the rate of photosynthetic CO2 assimilation in cucumber (Cucumis sastivus L.), intact plants were exposed, after the dark period, to light under different atmospheric CO2 concentrations (100, 400 and 2,000 microL x L(-1)) for 2 h. The in-vivo rates of net CO2 assimilation correlated with atmospheric CO2 concentrations. The CO2-fixation rate under 2,000 microL x L(-1) CO2 was 2.4- and 5.4-fold higher than under 400 and 100 microL x L(-1), respectively. Stomatal conductances and transpiration rates were almost identical after the 2-h light period under the various CO2 concentrations tested. Increasing atmospheric CO2 concentrations caused concomitant increases in the contents of starch and soluble sugars in the leaves and a decrease in the nitrate content. The activity and activation state of NR were both higher under elevated CO2 than under low CO2. High CO2 also enhanced NR-gene expression in the leaves. Sugars were supplied via roots to intact carbohydrate-starved plants and NR mRNA levels were analysed after 7 h. Fructose markedly stimulated NR-gene transcription in both leaves and roots. It is concluded that, in cucumber plants, the rate of CO2 assimilation controls the rate of nitrate assimilation by modulation of NR expression and activity, and that sugars are presumably involved as regulatory metabolites. PMID- 11216853 TI - Regulation of inducible adhesion molecule expression in human endothelial cells by grape seed proanthocyanidin extract. AB - Altered expression of cell adhesion molecule expression has been implicated in a variety of chronic inflammatory conditions. Regulation of adhesion molecule expression by specific redox sensitive mechanisms has been reported. Grape seed proanthocyanidins have been reported to have potent antioxidant properties. We evaluated the effects of grape seed proanthocyanidin extract (GSPE) on the expression of TNFalpha-induced ICAM-1 and VCAM-1 expression in primary human umbilical vein endothelial cells (HUVEC). GSPE at low concentrations (1-5 micrograms/ml), down-regulated TNFalpha-induced VCAM-1 expression but not ICAM-1 expression in HUVEC. Such regulation of inducible VCAM-1 by GSPE was also observed at the mRNA expression level. A cell-cell co-culture assay was performed to verify whether the inhibitory effect of GSPE on the expression of VCAM-1 was also effective in down-regulating actual endothelial cell/leukocyte interaction. GSPE treatment significantly decreased TNFalpha-induced adherence of T-cells to HUVEC. Although several studies have postulated NF-kappaB as the molecular site where redox active substances act to regulate agonist-induced ICAM-1 and VCAM-1 gene expression, inhibition of inducible VCAM-1 gene expression by GSPE was not through a NF-kappaB-dependent pathway as detected by a NF-kappaB reporter assay. The potent inhibitory effect of low concentrations of GSPE on agonist-induced VCAM-1 expression suggests therapeutic potential of this extract in inflammatory conditions and other pathologies involving altered expression of VCAM- 1. PMID- 11216854 TI - Induction of P-glycoprotein mRNA transcripts by cycloheximide in animal tissues: evidence that class I Pgp is transcriptionally regulated whereas class II Pgp is post-transcriptionally regulated. AB - P-glycoprotein (Pgp) are a small family of plasma membrane proteins capable of transporting substrates across cell membranes. Class I and class II Pgp are able to transport drugs and have been shown to mediate multidrug resistance (MDR). Class III Pgp is a long chain phospholipid transporter and does not mediate MDR. The expression and regulation of Pgp genes in animal tissues are not well understood. In this study, the protein synthesis inhibitor cycloheximide was used as a tool to understand Pgp gene expression and regulation in animal tissues. The sensitive RNase protection assay was used to detect changes in Pgp mRNA levels and nuclear run-on assay was used to determine whether transcription or post transcription is important. The results showed that cycloheximide significantly induced class II Pgp expression in all tissues examined. This was predominantly through post-transcriptional effect. In contrast, the relatively modest increase in class I Pgp expression by cycloheximide was found to be mainly due to increased transcriptional activity. On the other hand, cycloheximide induced class III Pgp expression in some tissues while caused decay of class III Pgp mRNA in other tissues. The transcriptional and post-transcriptional mechanisms exerted by cycloheximide on Pgp genes are discussed. These findings have implications for our understanding of gene regulation in animal tissues and MDR reversal strategies in vivo. PMID- 11216855 TI - Effects of sustained low-flow ischemia and reperfusion on Ca2+ transients and contractility in perfused rat hearts. AB - We investigated changes in cytoplasmic Ca2+ concentration ([Ca2+]i) and in left ventricular contractility during sustained ischemia and reperfusion in isolated beating rat hearts. Hearts from male Sprague-Dawley rats were perfused retrogradely and were loaded with 4 microM fura-2. Low-flow global ischemia was induced by reducing perfusion flow to 10% and by electric pacing. The hearts were exposed to ischemia for 10 min or 30 min and then reperfused. [Ca2+]i was measured by monitoring the ratio of 500 nm fluorescence excited at 340 and 380 nm while simultaneously measuring left ventricular pressure (LVP). To determine diastolic [Ca2+]i, background autofluorescence was subtracted. LVP rapidly decreased from 82.3+/-8.2 to 17.1+/-2.9 mmHg , whereas the amplitude of the Ca2+ transient did not change significantly during the first 1 min of ischemia. After 10 min of ischemia, the amplitude decreased to 60.8+/-10.6% (p < 0.05) and diastolic [Ca2+]i increased by 26.3+/-2.9% (p < 0.001) compared with the pre ischemic value (n = 8). When the hearts were reperfused after 10 min of ischemia, the amplitude of the Ca2+ transient and LVP recovered to 79.0+/-7.2% and 73.2+/ 7.5 mmHg, respectively. Whereas diastolic [Ca2+]i decreased to the preischemic value. In the hearts exposed to 30 min of ischemia (n = 10), diastolic [Ca2+]i increased even further by 32.7+/-5.3% at the end of ischemia and continued increasing during the 10 min of reperfusion by 42.6+/-15.6%. Six of 10 hearts developed ventricular fibrillation (VF) and intracellular Ca2+ overload after reperfusion. Recovery of LVP after reperfusion was significantly smaller in the hearts exposed to 30 min of ischemia than in the hearts exposed to 10 min of ischemia (58.9+/-11.7 vs. 97.2+/-3.0% of pre-ischemic value, p < 0.05). Diastolic [Ca2+]i also increased under hypoxic conditions (N2 bubbling) in this model. These results suggest that increases in diastolic [Ca2+]i might play an important role in myocardial contractile dysfunction and viability in ischemia-reperfusion injury. PMID- 11216857 TI - Mitochondrial ATP dependent potassium channels mediate non-ischemic preconditioning by tachycardia in dogs. AB - Brief episodes of tachycardia without myocardial ischemia prior to a coronary occlusion decrease myocardial infarct size in dogs. This non-ischemic preconditioning is mediated by adenosine. Because ischemic preconditioning is mediated through ATP dependent potassium channels, particularly the mitochondrial ones, we studied whether non-ischemic preconditioning is also mediated through these channels. In anesthetized dogs heart rate was kept constant at 120 cycles/min and aortic pressure changes were damped. Myocardial infarction was induced by occlusion of the anterior descending coronary artery for 60 min and reperfusion for 270 min. In a control group the infarct size (necrotic volume/risk region volume x 100) was 15.8+/-1.5%. Preconditioning with five periods of tachycardia, 5 min in duration each at 213 cycles/min with intervening periods of 5 min of basal heart rate at 120 cycles/min, reduced the infarct size by 45.6% (p < 0.05) with respect to the control group. This effect was completely reverted by the blockade of ATP dependent potassium channels with glibenclamide or 5 hydroxydecanoate (a specific blocker of mitochondrial ATP dependent potassium channels) prior to preconditioning. These effects were not due to differences in collateral flow, risk region size or hemodynamic variables between the groups. These results show that mitochondrial ATP dependent potassium channels mediate non-ischemic preconditioning by tachycardia in dogs. PMID- 11216856 TI - Homocysteine stimulates the expression of monocyte chemoattractant protein-1 in endothelial cells leading to enhanced monocyte chemotaxis. AB - Hyperhomocysteinemia has been identified as an independent risk factor for atherosclerosis. The infiltration of monocytes into the arterial wall is one of the key events during atherogenesis. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that stimulates the migration of monocytes into the intima of the arterial wall. The mechanism by which increased monocyte infiltration occurs in atherosclerotic lesions in patients with hyperhomocysteinemia has not been delineated. The objective of the present study was to investigate the effect of homocysteine on MCP-1 production in endothelial cells. Cells were incubated with homocysteine. The secretion of MCP-1 protein was significantly increased (195% as compared to the control) in cells treated with pathological concentrations of homocysteine. Such effect was accompanied by an increased expression of MCP-1 mRNA (176% as compared to the control) in endothelial cells which resulted in enhanced monocyte chemotaxis. The p38 MAP kinase as well as other members of the p38 MAP kinase pathway, including MKK3, MKK6, ATF-2 and Elk 1, were activated in homocysteine-treated cells. Homocysteine-induced MCP-1 expression and subsequent monocyte chemotaxis were blocked by a p38 MAP kinase inhibitor (SB203580) suggesting that the p38 MAP kinase pathway might be involved in homocysteine-induced MCP-1 expression in endothelial cells. In contrast, staurosporine, a protein kinase C inhibitor, had no effect on homocysteine induced MCP-1 expression. In conclusion, our results indicate that homocysteine stimulates MCP-1 expression in endothelial cells leading to enhanced monocyte chemotaxis. PMID- 11216858 TI - Cardiac chamber-specific alterations of ANP and BNP expression with advancing age and with systemic hypertension. AB - The present study determined cardiac chamber-specific alterations of the expression of the atrial and brain natriuretic peptide (ANP and BNP) genes with a small increase in age beyond adulthood and with systemic hypertension of intermediate duration. The expression distributions of these genes was determined using in situ hybridization in the right and left atria (RA and LA), and the right and left ventricles (RV and LV) in Wistar Kyoto rats (WKY) and age-matched Spontaneously Hypertensive rats (SHR) at ages 6 months (adult) and 8 months (advanced-age beyond adulthood). In all rat groups, both genes were expressed (ANP > BNP) in the LA and LV, and were not expressed in the RA and RV. The genes were expressed in the LA in all rat groups; the ANP, but not the BNP, expression increased with advancing age and with superimposed hypertension. They were expressed in the LV of the advanced-age WKY, adult and advanced-age SHR, but not in the adult WKY. The ANP mRNA labeling in the LA was diffuse and interspersed with dense accumulations, whereas BNP labeling was diffuse. The labeling of both genes in the form of sparse clusters was seen in the LV of the advanced-age SHR. Our study showed that ANP and BNP expression in left heart chambers increased with a small increase in age, with hypertension of intermediate duration, and with modest left ventricular hypertrophy. The chamber-specific expression distribution could be due to special groups of cardiac cells, or to local chamber specific factors. PMID- 11216859 TI - Receptor-Ck regulates membrane-bound 125 kDa protein having affinity for genomic sterol regulatory sequence. AB - The study addressed, to resolve the role of Receptor-Ck activation in the proteolytic maturation of 125 kDa (membrane bound) sterol regulatory element binding protein (SREBP), revealed that Receptor-Ck dependent signalling is not only responsible for the proteoloytic cleavage of this 125 kDa SREBP resulting in the generation of an active 47 kDa factor but also Receptor-Ck protein has high binding affinity for both 125 kDa SREBP as well as its cleaved 47 kDa product. Based upon these coupled with our earlier findings, we propose that Receptor-Ck may be regulating genes, have sterol regulatory element (SRE) in their promoter region, through the proteolytic maturation of 125 kDa SREBP into an active 47 kDa transcription factor. PMID- 11216860 TI - Expression of thrombospondin-1 in human hepatocarcinoma cell lines and its regulation by transcription factor Jun/AP-1. AB - Thrombospondin-1 (TSP-1) is a homotrimeric glycoprotein synthesized in a variety of normal and transformed cells, and secreted into the extracellular matrix. Based on its known effects on the tumor and endothelial cells, TSP-1 was implicated in the tumor growth and metastasis. In the present study, we have demonstrated the expression of TSP-1 in the human hepatocarcinoma cell lines. TSP 1 was detected in human hepatocarcinoma SK-HEP-1, Hep 3B and immortalized human liver Chang cells. Using two different cell lines, SK-HEP-1 and Hep 3B cells, we have studied effects of phorbol 12-myristate 13-acetate (PMA) on TSP-1 expression. TSP-1 synthesis was stimulated by PMA in both cell lines. When the cells were treated with PMA, the TSP-1 mRNA started to increase at 30 min and reached the maximal level at 6 h. TSP-1 induction by PMA was completely inhibited by the pre-treatment of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), a potent protein kinase C inhibitor. A TSP-1 promoter-luciferase reporter gene was transcriptionally activated by PMA, as well as by the expression of c-Jun. Among three putative AP-1 recognition sites on the TSP-1 promoter, a deletion of the 1st and 2nd sites caused loss of PMA-induced upregulation, while the 3rd site deletion showed no effect. In subsequent experiments, both the recombinant c-Jun and nuclear proteins induced by PMA have a stronger binding affinity for the 2nd AP-1 recognition site than the 1st and 3rd ones. Our study demonstrated that TSP 1 could be expressed and secreted by human hepatoma cell lines and its expression could be effectively regulated by PMA. We also suggest that AP-1 binding activity through the protein kinase C activation is a critical event for the TSP-1 gene expression and consequently affects production and processing of the protein. PMID- 11216861 TI - Cardiac myosin phenotype remodeling following chronic spinal transection. AB - Spinal transection results in profound neural and functional changes of the heart. However, phenotypic alterations in cardiac myosin heavy chains (MyHC) as a result of spinal transection have not been explored. Hearts were removed from 180 day old rats who had their spinal cords transected between T6 and T9 (ST; n = 10) and intact controls (IN; n = 9). Myosin was isolated from the left and right ventricles and separated into its respective heavy chain components (designated as alpha and beta) by SDS-PAGE. The resulting gels were scanned with a laser scanning densitometer to obtain relative concentrations of these two heavy chains. The left ventricles of the ST rats had a significantly higher (p < 0.05) alpha to beta ratio (10.89) than the intact controls (4.20), while the right ventricle of the ST rats had a significantly lower (p < 0.05) alpha to beta ratio (7.49) relative to intact controls (13.62). The left and right ventricular weight to body weight ratios were not different in ST compared to IN. Additionally, there were significant within group differences (p < 0.05) between the alpha and beta MyHC ratios for the left and right ventricles. These data suggest that 1) spinal transection causes remodeling of the right and left ventricles and 2) the two ventricles do not remodel as a unit. PMID- 11216862 TI - Intramitochondrial pyruvate attenuates hydrogen peroxide-induced apoptosis in bovine pulmonary artery endothelium. AB - In the hydrogen peroxide (H2O2) apoptosis model of the murine thymocyte, redox reactant and antioxidant pyruvate prevents programmed cell death. We tested the hypothesis that such protection was mediated, at least in part, via pyruvate handling by mitochondrial metabolism. Cultured bovine pulmonary artery endothelial cells were incubated for 30 min with 0.5 mM H2O2 in the absence and presence of 0.5 mM alpha-cyano-3-hydroxycinnamate, as a selective inhibitor of the mitochondrial pyruvate transporter. In controls H2O2 decreased cell viability by 30% within 24 h; this was associated with apoptosis-like bodies, nuclear condensation, and biochemical DNA damage consistent with programmed cell death. Pyruvate (0.1-20 mM) enhanced cell viability in a dose-dependent manner, with > or = 85% viable cells at > or = 3 mM and no DNA laddering, no positive nick-end labeling (TUNEL), and no detectable Annexin V or propidium iodide staining. In contrast, using > or = 5 mM L-lactate as a cytosolic reductant or acetate as a redox-neutral substrate, cell death increased to approximately 40%, which was associated with intense DNA laddering, positive TUNEL and Hoechst 33258 assays. Alpha-cyano-3-hydroxycinnamate alone did not significantly decrease endothelial viability but reduced viability from 85+/-3 to 71+/-4% (p = 0.023) in presence of 3 mM pyruvate plus H2O2; pathological cell morphology and DNA laddering under the same conditions suggested loss of pyruvate protection against apoptosis. Since alpha-cyano-3-hydroxycinnamate re-distributed medium pyruvate and L-lactate consistent with selective blockade of pyruvate uptake into the mitochondria, the findings support the hypothesis that pyruvate protection against H2O2 apoptosis is mediated in part via the mitochondrial matrix compartment. Possible mediators include anti-apoptotic bcl-2 and/or products of mitochondrial pyruvate metabolism such as citrate that affect metabolic regulation and anti-oxidant status in the cytoplasm. PMID- 11216863 TI - Selective impairment of protein kinase C isotypes in murine macrophage by Leishmania donovani. AB - Leishmania donovani, an obligate intracellular parasite resides and multiplies within macrophage of the reticuloendothelial system. The intracellular signalling mechanism involved in the impaired oxidative response in leishmaniasis has not yet been clearly established. Generation of superoxide anion (O2-) is supposed to be the first line of host defence during microbial invasion. We found a substantial inhibition of superoxide anion generation in parasitized macrophages, which was just the reverse in case of macrophages challenged with Lipophosphoglycan (LPG) deficient attenuated leishmanial parasite UR-6. The generation of O2- essentially needs the prior activation of protein kinase C (PKC) mediated phosphorylation events. Our study proposed that phosphorylation of 67, 54, 47 and 36 kDa proteins was attenuated during infection. This was supported by PKC activity study, where Ca-dependent PKC activity was inhibited but, Ca-independent PKC activity was enhanced. This result was further confirmed by using isotype specific pseudosubstrate inhibitors of Ca-dependent PKC beta and Ca-independent PKC zeta. Application of beta-pseudosubstrate could not alter the Ca-dependent PKC activity but zeta-pseudosubstrate inhibited the Ca-independent PKC activity in infected macrophages. Our immunoblot analysis with specific antibody against PKC beta and PKC zeta isotypes showed down regulation of PKC beta-II expression with concomitant induction of PKC zeta. Such inhibition of Ca dependent PKC beta was reversed in macrophages treated with UR-6. Taken together, our observations revealed that infection with L. donovani selectively attenuates both the expression and activity of Ca-dependent PKC beta. PMID- 11216865 TI - Hypothalamic GABA receptor functional regulation and liver cell proliferation. AB - GABAergic alterations in hypothalamus during compensatory hyperplasia after partial hepatectomy (PH), lead nitrate (LN) induced direct hyperplasia and N nitrosodiethylamine (NDEA) induced neoplasia in liver were investigated. Serum GABA levels were increased in all 3 experimental groups compared with the control. GABA content decreased in hypothalamus of PH and NDEA treated rats, while it increased in LN treated rats. GABA(A) receptor number and affinity in hypothalamic membrane preparations of rats showed a significant decrease in PH and NDEA treated rats, while in LN treated rats the affinity increased without any change in the receptor number. The GABA(B) receptor number increased in PH and NDEA treated rats, while it decreased in LN treated rats. The affinity of the receptor also increased in NDEA treated rats. Plasma NE levels showed significant increase in PH and NDEA rats compared with the control while it decreased in LN treated rats. The results of the present study suggests that liver cell proliferation is influencing the hypothalamic GABAergic neurotransmission and these changes regulate the hepatic proliferation through the sympathetic stimulation. PMID- 11216864 TI - Short-term gemfibrozil treatment reverses lipid profile and peroxidation but does not alter blood glucose and tissue antioxidant enzymes in chronically diabetic rats. AB - In this study, we investigated the efficiency of short-term treatment with gemfibrozil in the reversal of diabetes-induced changes on carbohydrate and lipid metabolism, and antioxidant status of aorta. Diabetes was induced by a single injection of streptozotocin (45 mg/kg, i.p.). After 12 weeks of induction of diabetes, the control and diabetic rats were orally gavaged daily with a dosing vehicle alone or with 100 mg/kg of gemfibrozil for 2 weeks. At 14 weeks, there was a significant increase in blood glucose, plasma cholesterol and triglyceride levels of untreated-diabetic animals. Diabetes was associated with a significant increase in thiobarbituric acid reactive substances (TBARS) in both plasma and aortic homogenates, indicating increased lipid peroxidation. Diabetes caused an increase in vascular antioxidant enzyme activity, catalase, indicating existence of excess hydrogen peroxide (H2O2). However, superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) activities in aortas did not significantly change in untreated-diabetic rats. In diabetic plus gemfibrozil group both plasma lipids and lipid peroxides showed a significant recovery. Gemfibrozil treatment had no effect on blood glucose, plasma insulin and vessel antioxidant enzyme activity of diabetic animals. Our findings suggest that the beneficial effect of short-term gemfibrozil treatment in reducing lipid peroxidation in diabetic animals does not depend on a change of glucose metabolism and antioxidant status of aorta, but this may be attributed to its decreasing effect on circulating lipids. The ability of short-term gemfibrozil treatment to recovery of metabolism and peroxidation of lipids may be an effective strategy to minimize increased oxidative stress in diabetic plasma and vasculature. PMID- 11216867 TI - Radiomodification of glyoxalase I in the liver and spleen of mice: adaptive response and split-dose effect. AB - Glyoxalase system, particularly glyoxalase I (Gly I) plays an important role in regulation of cell division and is considered to be a metabolic indicator of cell proliferation. The glyoxalase system is likely to have a close link with cellular radiosensitivity. Therefore, we have examined the effect of adaptive and split dose of y-rays on the activity of Gly I in the liver and spleen of mice. For the adaptive response studies, mice pre-treated with a conditioning dose of 0.5 Gy were given a challenging dose of 4 Gy at varying time intervals. In the split dose studies, a dose of 4 Gy was delivered into two equal fractions and spaced at different time intervals. The results show that pre-exposure to a conditioning dose or the fractionation of total dose decreased the specific activity of Gly I in the liver and spleen of mice. The decreased activity of Gly I was suggestive of protective action induced by the conditioning dose and fractionation of dose. The similar pattern of radiation response of Gly I probably supported the possibility of involvement of a common pathway in the radiation-induced adaptive and split-dose effect. From these observations a close link between the Gly I and the adaptive-response as well as the split-dose effect is speculated. Since, the glyoxalase system is vital for a variety of biological functions including cell division and repair, the present findings may have relevance in understanding the dose-fractionation as well as the biological defence induced by low doses of radiations. PMID- 11216868 TI - Brain plasma membrane Na+,K+-ATPase is inhibited by acetylated tubulin. AB - Membranes from brain tissue contain tubulin that can be isolated as a hydrophobic compound by partitioning into Triton X-114. The hydrophobic behavior of this tubulin is due to the formation of a complex with the alpha-subunit of Na+,K+ ATPase. In the present work we show that the interaction of tubulin with Na+K+ ATPase inhibits the enzyme activity. We found that the magnitude of the inhibition is correlated with: (1) concentration of the acetylated tubulin isoform present in the tubulin preparation used, and (2) amount of acetylated tubulin isoform isolated as a hydrophobic compound. In addition, some compounds involved in the catalytic action of Na+K+-ATPase were assayed to determine their effects on the inhibitory capability of tubulin on this enzyme. The inhibitory effect of tubulin was only slightly decreased by ATP at relatively low nucleotide concentration (0.06 mM). NaCl (1-160 mM) and KCl (0.2-10 mM) showed no effect whereas inorganic phosphate abolished the inhibitory effect of tubulin in a concentration-dependent manner. PMID- 11216866 TI - Bezafibrate induces acyl-CoA oxidase mRNA levels and fatty acid peroxisomal beta oxidation in rat white adipose tissue. AB - Rats treated with bezafibrate, a PPAR activator, gain less body weight and increase daily food intake. Previously, we have related these changes to a shift of thermogenesis from brown adipose tissue to white adipose tissue attributable to bezafibrate, which induces uncoupling proteins (UCP), UCP-1 and UCP-3, in rat white adipocytes. Nevertheless, UCP induction was weak, implying additional mechanisms in the change of energy homeostasis produced by bezafibrate. Here we show that bezafibrate, in addition to inducing UCPs, modifies energy homeostasis by directly inducing aco gene expression and peroxisomal fatty acid beta oxidation in white adipose tissue. Further, bezafibrate significantly reduced plasma triglyceride and leptin concentrations, without modifying the levels of PPARgamma or ob gene in white adipose tissue. These results indicate that bezafibrate reduces the amount of fatty acids available for triglyceride synthesis in white adipose tissue. PMID- 11216870 TI - L-asparaginase of Thermus thermophilus: purification, properties and identification of essential amino acids for its catalytic activity. AB - L-asparaginase EC 3.5.1.1 was purified to homogeneity from Thermus thermophilus. The apparent molecular mass of L-asparaginase by SDS-PAGE was found to be 33 kDa, whereas by its mobility on Sephacryl S-300 superfine column was around 200 kDa, indicating that the enzyme at the native stage acts as hexamer. The purified enzyme showed a single band on acrylamide gel electrophoresis with pI = 6.0. The optimum pH was 9.2 and the Km for L-asparagine was 2.8 mM. It is a thermostable enzyme and it follows linear kinetics even at 77 degrees C. Chemical modification experiments implied the existence ofhistidyl, arginyl and a carboxylic residues located at or near active site while serine and mainly cysteine seems to be necessary for active form. PMID- 11216869 TI - Post-transcriptional control of catalase expression in garlic-treated rats. AB - Regulation of catalase (CAT) expression, a major antioxidant enzyme that detoxifies H2O2, is very complex. Garlic is effective to prevent or ameliorate oxidative stress probably through its intrinsic antioxidant properties and/or to its ability to modify antioxidant enzyme expression. In this paper we studied the effect of a 2% garlic diet on the renal and hepatic CAT expression (mRNA levels, and enzyme activity, content, synthesis, and degradation). The study was made 2 weeks after feeding rats with a 2% garlic diet. CAT activity and content were measured by a spectrophotometric method and Western blot, respectively. CAT mRNA levels and CAT synthesis (k(s)) and degradation (kD) in vivo were measured by Northern blot and kinetic of reappearance of CAT activity after aminotriazole injection, respectively. Garlic-treatment decreased CAT activity and content, and CAT mRNA levels were unchanged in both tissues. k(s) decreased and kD remained unchanged in kidney and liver. The decrease in k(s) without changes in kD and CAT mRNA levels could explain the low CAT expression in garlic-fed rats. In vivo H2O2 generation in kidney and liver was markedly decreased in garlic-fed rats which could be due to a direct antioxidant effect of garlic. This may be the initial event in the garlic-fed rats that leads to the decreased CAT expression. Our data strongly suggest that the diminished renal and hepatic CAT expression in garlic fed rats is mediated by post-transcriptional changes (mainly low translational efficiency) which could be an adaptation to the low H2O2. PMID- 11216871 TI - Influence of breast-feeding on the production of cytokines. AB - PROBLEM: Recently, we reported increases in the production of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and IL-4 during the postpartum period. The present study was undertaken to investigate whether these increases might be explained by increased prolactin while breast-feeding. METHOD: Whole blood from 41 women who were breast-feeding, 13 women not breast-feeding, and 31 healthy non pregnant women was stimulated with phorbol 12-myristate 13-acetate and ionomycin, and the levels of cytokines in the supernatant were measured by enzyme-linked immunosorbent assay. Their serum levels of prolactin were measured by enzyme immunoassay. RESULTS: Increases in IFN-gamma, IL-2, IL-4, and IL-10 production were observed in women who were breast-feeding but not in women who were not breast-feeding. Serum levels of prolactin correlated with the levels of IFN-gamma in culture supernatant. CONCLUSIONS: These results suggest that breast-feeding induces production of cytokines and that IFN-gamma production is enhanced by physiological concentrations of prolactin. PMID- 11216872 TI - HLA-G expression by tumors. AB - PROBLEM: It has been proposed that the expression of the non-classical MHC class I antigen, HLA-G, by trophoblast is one mechanism by which the placenta evades attack by maternal uterine NK cells. A similar mechanism is thought to be operative in the escape from immunosurveillance by tumor cells. However, data on the expression of HLA-G by tumor cells are highly conflicting. METHOD OF STUDY: In the present study, we have examined tissue sections from a wide variety of tumors by immunohistology and also several cell lines by flow cytometry and RT PCR. Whilst very faint bands were detected in three cell lines (hepG2, Mead, CaSki) by RT-PCR, no tumors or cell lines were observed to express HLA-G protein. Furthermore, we found that tumor deposits are not usually infiltrated by NK cells. CONCLUSION: Our observations, therefore, do not support the proposal that tumor cells express HLA-G in order to evade host NK cell cytolysis. PMID- 11216874 TI - Immunologic detection of placental lactogen during pregnancy in a mouse model: a preliminary report. AB - PROBLEM: To establish a rapid test differentiating ectopic from failed intrauterine gestation, using placental lactogen (PL) as a marker for placental cells. METHOD OF STUDY: Sixteen Swiss Webster mice had synchronized ovulation and were mated. Eight mice were unmated controls. Study and control mice were sacrificed at 5, 7, 9. and 11 days gestation. Uterine sections were tested for PL by immunofluorescent antibody assay, enzyme-linked immunosorbent assay, and dot blot analysis. Human endometrial samples from a missed abortion and a nonpregnant woman were also tested. RESULTS: Placental lactogen was detectable only in pregnant uterine samples (placental cells only) by all assays and was absent in the endometial glandular cells of nonpregnant uterine samples. CONCLUSION: Three methods detected placental lactogen in the pregnant mouse and human tissue. This is the first step towards developing a reliable clinical test for human endometrial samples from early pregnancy to differentiate early abortion from ectopic pregnancy. PMID- 11216873 TI - FAS/FAS ligand interaction at the placental interface is not required for the success of allogeneic pregnancy in anti-paternal MHC preimmunized mice. AB - PROBLEM: FAS ligand (FASL) induces apoptosis in FAS+ T cells. FAS-FASL interaction can explain tolerance of some types of allografts. Do similar interactions prevent rejection of the fetal allograft and transplacental passage of maternal T cells capable of causing GvH leading to runting? METHOD OF STUDY: We examined growth of subcutaneous EL-4 (H-2b) tumor cells in syngeneic MRL.lpr/lpr mice mated with syngeneic MRL.lpr/lpr or allogeneic C57/B1/6.lpr/lpr males. Lpr/lpr mice lack FAS and their T cells should remain effective at the fetomaternal interface. In some studies, the mice were preimmunized against C57B1/6 to enhance the likelihood of fetal rejection and/or runting. Cytotoxic lymphocyte (CTL) activity in the spleens was assessed using a 51Cr-release assay. Birth weights and weights at weaning were measured. RESULTS: Tumor rejection was delayed by about 3 days in allopregnant lpr/lpr females compared to syngeneic pregnant females occurred, but tumors were rejected and in a secondary fashion with minimal delay allopregnant females preimmunized to H-2b. CTL activity was present more in decidua than in spleen in preimmunized mice, and allopregnancy failed to reduce this activity. No neonates born to preimmunized or control lpr/lpr mothers developed runt disease. Indeed, the birth weight was greater for immunized females, but at 10 weeks, the difference compared to non-immunized females disappeared. CONCLUSIONS: FAS/FASL interaction between FAS+ T cells and FASL+ fetal trophoblasts at the fetomaternal interface is not mandatory for successful allopregnancy. The potential roles of other apoptosis-induction mechanisms at the fetomaternal interface, such as TNF/TRAIL, require critical testing before enthusiasm is merited. It maybe necessary to eliminate all such mechanisms to show a deleterious effect on pregnancy. Spontaneous deletion of all pathways seems a priori unlikely to occur, and hence, of dubious relevance to fetal loss. PMID- 11216875 TI - Localization and distribution of platelet activating factor receptors in the mouse ovary and oviduct during the estrous cycle and early pregnancy. AB - PROBLEM: This study determined platelet activating factor (PAF) binding to ovaries and oviduct tissues to identify the location of PAF tissue interaction. METHOD: Mouse ovaries and oviducts taken during the estrous cycle and days 1, 4 and 7 post-conception (pc) were analyzed by [3H]PAF binding using frozen sections and autoradiography. RESULTS: For the outer epithelium of estrous and metestrous ovaries there was no significant difference in PAF binding (P>0.05); however, both stages were significantly different from proestrous (P<0.001). Ovarian stroma PAF binding was significantly higher (P<0.001) at estrous than metestrous, with no PAF binding at proestrous. Binding of PAF to estrous ovarian follicles was significantly greater (P<0.001) than at proestrous and metestrous. Estrous oviduct binding of PAF was significantly increased for stroma, inner epithelium and lumen (P<0.001 in all cases). At days 1 and 7 pc, all ovarian tissues had the greatest PAF binding with day 4 pc failing to bind PAF except for a significant decrease in corpora luteal binding (P<0.001). Oviduct binding of PAF was greatest at day 1 pc. CONCLUSION: Ovarian and oviduct PAF receptor expression corresponds to peak embryo PAF synthesis and establishes the basis for PAF PAF receptor mediated early pregnancy signaling system. PMID- 11216876 TI - Hypercoagulable thrombophilic defects and hyperhomocysteinemia in patients with recurrent pregnancy loss. AB - PROBLEM: Placental perfusion may be compromised by increased thrombosis that leads to pregnancy complications and recurrent pregnancy loss (RPL). Since heritable thrombophilic defects and hyperhomocysteinemia are associated with increased thrombosis, their prevalence was evaluated in RPL patients with special emphasis on combinations of the above pathologies. METHODS OF STUDY: Evaluation of the prevalence of heritable thrombophilic defects (protein S, protein C, anti thrombin III deficiency, and the mutations for factor V Leiden, methylenetetrahydrofolate reductase [MTHFR], and prothrombin gene), hyperhomocysteinemia. and combinations of these pathologies in 36 non-pregnant recurrent aborters compared with 40 parous women. RESULTS: We found a relatively high prevalence of deficiencies of plasma coagulation proteins in RPL patients compared with the controls. A non-significant different increase in factor V Leiden mutation was detected (6/36 [16%] compared with 2/40 [5%] in the control group, P = 0.14]. Hyperhomocysteinemia was found in 31% of the RPL patients. MTHFR mutation homozygosity was found in 6/36 (16%) of the aborting patients. Combinations of hyperhomocysteinemia and MTHFR mutation were found in three patients, with folate deficiency in two patients, and with B12 deficiency in three. CONCLUSIONS: Combinations of gene mutations, plasma protein deficiencies, and hyperhomocysteinemia, which are associated with an increased thrombotic risk, are more common in RPL patients compared with controls. Large-scale prevalence studies are needed in order to draw conclusions as to the causative relation of such a condition and RPL. PMID- 11216877 TI - The association between anti-thyroid antibodies and pregnancy loss. AB - The incidence of thyroid autoantibodies in women with recurrent fetal loss, infertility or women who miscarried appears to be increased compared with controls of reproductive age without previous abortions. There are few working hypotheses concerning the asociation between anti-thyroid antibodies and the increased risk for pregnancy loss. The first hypothesis suggests that women with high titers of anti-thyroid antibodies have underlying very mild thyroid "under function". Another theory views the anti-thyroid antibodies as simply secondary markers of a predisposition of autoimmune disease rather than the actual cause of pregnancy loss. An evolutionary explanation suggests that reproductive problems in women with high titers of autoantibodies exist in order to prevent the transmission of autoimmune genes to the next generation. The reason for the association between pregnancy loss and thyroid immunity is still not clear. The working hypotheses above supply multi-factorial explanations, which could act together, may even be in synergy, as the propulsion for the pregnancy loss. Until today the mechanism by which anti Tg are responsible for pregnancy loss is not clear. Induced animal models with high titier of anti Tg could provide direct evidence for the pathogenic role of anti-thyroid antibodies and the mechanism that is responsible for the pregnancy loss in autoimmune thyroiditis. In the current presentation we describe data concerning the association between anti thyroid antibodies and pregnancy loss, and hypothesis which explains this association. PMID- 11216878 TI - Differential expression and regulation of inducible nitric oxide synthase (iNOS) mRNA in human trophoblasts in vitro. AB - OBJECTIVES: To determine the expression of inducible nitric oxide synthase (iNOS) in human trophoblast and to examine the possible regulation of iNOS gene by cytokines. MATERIALS AND METHODS: Total RNA was isolated from: 1) homogenized placental tissue; from 2) isolated and purified cytotrophoblast cells; and 3) cytotrophoblast and syncytiotrophoblast cells treated with cytokines in vitro. RNA was reverse transcribed and amplified by polymerase chain reaction, using specific primers for iNOS. Trophoblast cells were treated in vitro by interferon gamma (IFN-gamma) in a dose of 10 ng/mL, Interleukin 1beta (IL-1beta) (4 ng/mL) and leukemia inhibitory factor (LIF) (1 ng/mL). Trophoblasts were also subjected to immunocytochemistry using iNOS-specific antibody to detect iNOS protein expression in these cells. RESULTS: The expression of iNOS mRNA was found both in placental tissue and isolated cytotrophoblast cells. In culture, the highly differentiated syncytiotrophoblast expressed more mRNA than cytotrophoblast cells. IFN-gamma and LIF, but not IL-1beta, induced iNOS mRNA expression in trophoblast cells in vitro. The effects of these cytokines on iNOS mRNA were only observed in syncytiotrophoblast cells, but not in cytotrophoblast cells. Immunocytochemical staining confirmed the trophoblast cells as a major source of the iNOS synthase production. CONCLUSIONS: 1) Human trophoblast cells are able to express the iNOS mRNA, hence suggesting a role for NO in placental growth and function. 2) LIF and IFN-gamma, but not IL-1beta, induce the iNOS mRNA expression in syncytiotrophoblast cells in vitro, suggesting possible similar regulatory mechanisms in vivo. 3) This study, for the first time, demonstrates the stimulating effect of LIF on iNOS gene expression in human tissue. PMID- 11216879 TI - Comparative effect of danazol and a GnRH agonist on monocyte chemotactic protein 1 expression by endometriotic cells. AB - PROBLEM: Endometriosis is associated with a chronic inflammatory process, and the increased number of activated peritoneal macrophages is one of the major hallmarks of this process. The medical treatment of the disease, which is based on the creation of an hypoestrogenic milieu unfavorable to the growth of endometriotic lesions, is often associated with a reduced peritoneal inflammation. The aim of this study was to investigate the ability of current therapeutic agents to modulate, through a direct mechanism, the expression by endometriotic cells of monocyte chemotactic protein-1 (MCP-1), a chemokine endowed with the potent faculty of recruiting and activating macrophages. METHOD OF STUDY: Cells were stimulated with interleukin-1 beta (IL-1beta) to induce MCP 1 expression. MCP-1 protein secretion and mRNA steady-state levels were evaluated by ELISA and northern blot, respectively. RESULTS: Our results show that danazol concentrations (10(-7) -10(-5) M), taking into account the therapeutic levels found in the plasma of treated patients, inhibited MCP-1 protein and mRNA steady state levels in endometriotic cells, whereas buserelin acetate (0.1-10 ng/mL), a GnRH agonist, had no significant effect. Dexamethasone, an anti-inflammatory glucocorticoid, used at concentrations varying between 10(-12) and 10(-6) M, also displayed a dose-dependent inhibitory action. CONCLUSIONS: These results put into prominence the capability of danazol to directly inhibit the expression of a potent monocyte chemotactic and activating factor by ectopic endometrial cells shedding more light on the mechanisms underlying the clinical effects of hormonal therapeutic agents used in the treatment of endometriosis. PMID- 11216880 TI - Human leukocyte antigen-G-expressing cells differently modulate the release of cytokines from mononuclear cells present in the decidua versus peripheral blood. AB - PROBLEM: To better understand the role of human leukocyte antigen (HLA)-G in regulating the T helper (Th)1/Th2 cytokine balance, one of key conditions in determining the fate of pregnancy, we asked whether the presence of HLA-G protein altered the release of cytokines from both decidual mononuclear cells and peripheral blood mononuclear cells (PBMCs). METHOD OF STUDY: The amounts of cytokines released from decidual mononuclear cells and PBMCs were compared in the presence or absence of HLA-G-expressing cells. RESULTS: When cocultured with HLA G-expressing cells, the amounts of tumor necrosis factor-alpha and interferon gamma released from decidual mononuclear cells and PBMCs were decreased, while the amounts of interleukin (IL)-4 from PBMCs was increased, with IL-4 release from decidual mononuclear cells being unchanged. CONCLUSIONS: Upon contact with HLA-G, decidual mononuclear cells, and PBMCs as well, modulate their ability to release cytokines in a way that may shift the Th1/Th2 balance towards relative Th2 dominance, suggesting a role for HLA-G in maintaining pregnancy. PMID- 11216881 TI - Semantic knowledge and episodic memory for faces in semantic dementia. AB - Previous studies have documented poor recognition memory for faces in patients with semantic dementia. Preserved face recognition memory was found in this study, however, so long as atrophy was confined predominantly to the left temporal lobe. Patients with structural damage to the right temporal lobe were typically impaired, with the status of the hippocampus and parahippocampal gyrus (including the perirhinal cortex) on the right being critical. Two single-case studies of patients with predominantly left temporal lobe pathology confirmed good recognition memory for famous faces, even if semantic knowledge about the celebrities depicted was severely degraded. An effect of semantic knowledge on recognition memory became apparent only when perceptually different photographs of the famous people were used at study and test. These results support the view that new episodic learning typically draws on information from both perceptual and semantic systems. PMID- 11216883 TI - Short-term memory for serial order in schizophrenia: a detailed examination of error types. AB - Cognitive deficits in schizophrenia have been associated with working memory problems. Schizophrenic patients (n = 24) and controls (n = 29) participated in simple short-term memory tasks, recalling a list of letters from the first to last item in the order of presentation. The authors hypothesized that deficient sequential representations would increase movement errors (e.g., ABCD being recalled as ABDC) or intrusion errors (e.g., ABCD being recalled as ABCX), whereas simple trace decay would lead to omission errors (e.g., ABCD being recalled as ABC_). Patients made disproportionately more omissions toward the end of 6-item lists. There were no group differences in movements or intrusions as a function of serial position. Schizophrenic patients' limited short-term memory span may be due to greater forgetting during recall and not to a selective deficit in the mechanisms responsible for maintaining serial order information. PMID- 11216882 TI - Neural substrates of mathematical reasoning: a functional magnetic resonance imaging study of neocortical activation during performance of the necessary arithmetic operations test. AB - Brain activation was examined using functional magnetic resonance imaging during mathematical problem solving in 7 young healthy participants. Problems were selected from the Necessary Arithmetic Operations Test (NAOT; R. B. Ekstrom, J. W. French, H. H. Harman, & D. Dermen, 1976). Participants solved 3 types of problems: 2-operation problems requiring mathematical reasoning and text processing, 1-operation problems requiring text processing but minimal mathematical reasoning, and 0-operation problems requiring minimal text processing and controlling sensorimotor demands of the NAOT problems. Two operation problems yielded major activations in bilateral frontal regions similar to those found in other problem-solving tasks, indicating that the processes mediated by these regions subserve many forms of reasoning. Findings suggest a dissociation in mathematical problem solving between reasoning, mediated by frontal cortex, and text processing, mediated by temporal cortex. PMID- 11216884 TI - The development of a quantitative electroencephalographic scanning process for attention deficit-hyperactivity disorder: reliability and validity studies. AB - The development of a quantitative electroencephalographic (QEEG)-based procedure for use in the assessment of attention deficit-hyperactivity disorder (ADHD) was examined through a series of studies investigating test reliability and validation issues. This process, involving a spectral analysis of the electrophysiological power output from a single, midline, central location (the vertex), was conducted in 469 participants, 6 to 20 years of age, classified as ADHD, inattentive type; ADHD, combined type; or control. The results indicated that the QEEG scanning procedure was reliable (r = .96), was consistent with the Attention Deficit Disorders Evaluation Scale (S. B. McCarney, 1995) and the Test of Variables of Attention (L. M. Greenberg, 1994; chi-square, p < .01), and differentiated participants with ADHD from a nonclinical control group (p < .001). The sensitivity of the QEEG-derived attentional index was 90%; the specificity was 94%. PMID- 11216885 TI - Olfactory-evoked regional cerebral blood flow in Alzheimer's disease. AB - Olfaction is impaired in Alzheimer's disease (AD). It was hypothesized that AD would reduce olfactory-evoked perfusion in mesial temporal olfactory (piriform) cortex, where neuropathology begins. Seven AD patients and 8 elderly controls (ECs) underwent olfactory threshold and identification tests and olfactory stimulation during positron emission tomography. Odor identification was impaired in AD, but threshold was not. Olfactory stimulation in ECs activated right and left piriform areas and right anterior ventral temporal cortex. AD patients had less activation in right piriform and anterior ventral temporal cortex but not in the left piriform area. Although orbital cortex did not activate in ECs, there was a significant between-groups difference in this area. Right piriform activation correlated with odor identification. Impaired odor identification likely reflects sensory cortex dysfunction rather than cognitive impairment. Given olfactory bulb projections to the mesial temporal lobe, olfactory stimulation during functional imaging might detect early dysfunction in this region. PMID- 11216886 TI - Is the dissociability of working memory systems for name identity, visual-object identity, and spatial location maintained in old age? AB - The dissociability of working memory for name identity (verbal information), visual objects, and spatial location was explored in 3 experiments. Consistent with previous results, the 3 working memory systems were dissociable in younger adults. Both younger and older adults showed involvement of name identity in an object identity task, and older adults showed this involvement in a spatial memory task. Results were interpreted as showing that the systems are generally separable but that involvement of 1 with another is possible and more likely in older adults. A 4th, correlational study showed that there is generalized decline in working memory systems in old age, with the age differences in memory mediated to a moderate extent by age-related differences in speed of processing. It was speculated that the specific, possibly strategic changes are independent of and take place against a backdrop of generalized loss of nervous system integrity. PMID- 11216887 TI - Impaired perception of facial emotions following bilateral damage to the anterior temporal lobe. AB - Two patients (E.P. and G.T.) were previously described with damage to amygdala and anterior temporal cortex (S.B. Hamann et al., 1996). Both rated emotions in facial expressions normally (the rating task) when the data analysis followed a method that had revealed an impairment in the well-studied patient S.M. The present study reports findings for a 3rd patient (G.P.) with the rating task and reexamines the data for E.P. and G.T. All 3 patients were also given a labeling task in which they selected, from a list of 6 words, which word they thought best described the emotion expressed by a face. All 3 patients were unmistakably impaired on both tasks. However, the impairment exhibited by these patients is different from S.M.'s impairment. The difference may depend on the etiology (congenital vs. adult-onset lesion) or the site of the damage (relatively selective amygdala damage vs. damage to amygdala as well as anterior temporal cortex). PMID- 11216888 TI - Differences between nouns and verbs after anterior temporal lobectomy. AB - To test the claim that lesions of left anterior and middle temporal cortical structures specifically impair processing of nouns but not verbs, 56 left hemisphere-language-dominant patients who had undergone anterior temporal lobectomy (ATL) completed tasks assessing confrontation naming of pictured objects and actions, generation of synonyms for nouns and verbs, and semantic lexical judgments about nouns and verbs. Compared with right ATL patients, left ATL patients were impaired across different tasks that assessed naming and comprehension of high-imageability as well as low-imageability nouns. These groups did not differ, however, in verb naming or comprehension on most tasks. Results are consistent with the hypothesized specialization of left temporal lobe structures for processing nouns and suggest that naming problems commonly seen after left ATL extend beyond difficulties with retrieving object names and may be related to subtle disturbances in comprehension of the meanings underlying nominal word forms. PMID- 11216889 TI - Memory for content and source in temporal lobe patients. AB - Left and right temporal lobectomy patients and normal controls were tested in a memory task for which the to-be-remembered items were simple actions involving small objects. Participants either performed the actions, perceived the experimenter performing the actions, or imagined themselves performing the actions. The patients were deficient relative to the controls at remembering the actions and at remembering whether the actions were performed, perceived, or imagined. These results are interpreted as suggesting that the temporal lobes are involved in memory for the source as well as the content of past experiences. PMID- 11216890 TI - Short-term memory for duration and distance in humans: role of the hippocampus. AB - Control participants and hypoxic participants with bilateral hippocampal damage were tested for short-term memory (STM) for presentation duration of a single object, STM for a single object, STM for spatial distance information, and time estimation. Delays of 1, 4, 8, 12, or 16 s were used for all the STM and time estimation tests. Results indicated that relative to controls, hypoxic participants were significantly impaired for STM for duration and distance information at the long but not short delays. Similarly, time estimation was accurate only to 8 s for hypoxic participants, but STM for a single object was only mildly affected. Results suggest that the hippocampus may be required for the processing of spatial and temporal STM information. PMID- 11216891 TI - H.M. revisits the Tower of Hanoi Puzzle. AB - To address the controversy of whether an intact procedural memory system alone can support the learning of the recursive strategy for solving the Tower of Hanoi Puzzle, the authors tested 2 amnesic patients, H.M. and P.N. Contrary to the report of N. J. Cohen, H. Eichenbaum, B. S. Deacedo, and S. Corkin (1985), both patients failed to master the recursive strategy under the active-interaction condition. In contrast, normal control participants were able to master the strategy under identical testing conditions. The failure of H.M. and P.N. could not be attributed to the differences between the original and current testing conditions. In addition, neither patient showed frontal lobe dysfunction or impairment in procedural memory. Together with evidence provided by theoretical analyses of this puzzle as well as studies on normal participants, the authors conclude that declarative memory plays a vital role in the acquisition of the recursive strategy for solving the Tower of Hanoi Puzzle. PMID- 11216892 TI - Reflective and reflexive action control in patients with frontal brain lesions. AB - Two types of action control derived from the model of action phases (H. Heckhausen & P. M. Gollwitzer, 1987) were analyzed in patients with frontal lesions, patients with nonfrontal lesions, and university students. In Study 1, reflective action control in terms of goal selection was assessed, and impaired deliberation was found in patients with frontal lesions. Study 2 assessed reflexive action control in terms of automatic action initiation as a result of forming implementation intentions (P. M. Gollwitzer, 1999). All participants sped up their responses to critical stimuli by forming implementation intentions. Moreover, lesion patients with weak performances on the Tower of Hanoi (TOH) task did worse than patients with strong TOH performances in Study 1 but better than control participants in Study 2. Findings are interpreted as a functional dissociation between conscious reflective action control and automatic reflexive action control. PMID- 11216893 TI - Human genetics in health care. AB - The Human Genome Project, the mapping of our 100,000 genes and the sequencing of all of our DNA, will have major impact on biomedical research and the whole of therapeutic and preventive health care. The tracing of genetic diseases to their molecular causes is rapidly expanding diagnostic and preventive options, while the increased insights into molecular pathways open tremendous perspectives for pharmacological and genetic therapies. The design of animal model systems for the functional study of disease and development and the use of bioinformatics and biostatistics to improve our pattern recognition abilities are greatly accelerating progress. However, the optimal value from the current explosion of 'data mining' possibilities will only be gained when the basic data are made and kept publicly accessible, while at the same time safeguarding the protection of intellectual property arising from downstream inventions. This is one of the goals of the international Human Genome Organisation, established 10 years ago to assist coordinating data acquisition and exchange and societal implementation of the genome project. Additional points of major attention in this historic endeavour are the safeguarding of a worldwide balance in the contribution and benefits to countries and populations, the prevention of stigmatisation and discrimination of individuals and groups and the maintenance of respect for the diversity of our world's cultures and traditions. CONCLUSION: The acquisition and use of genomic information for health care benefit should be seen in the light of a worldwide improvement without prejudice. PMID- 11216895 TI - Methods in clinical molecular genetics. AB - Mutation detection is fundamental throughout biology, but especially so in medicine and medical research, particularly in gene discovery and cancer diagnostics. Current methods are unsatisfactory due to a range of reasons, but particularly due to cost and lack of convenience. The current methods are reviewed and their advantages and disadvantages discussed. The high profile chip technology whilst making an enormous impact in expression studies is more problematic for mutation detection, especially for unknown mutations and the problems are discussed. Finally, once mutations are discovered they need documenting accurately and the efforts of the Human Genome Organisation mutation database initiative due this direction are discussed. CONCLUSION: Current methods of mutation analysis, although unsatisfactory, are reviewed and the impact of new technologies assessed. PMID- 11216894 TI - Disease-causing mutations in the human genome. AB - A considerable number of gene mutations has now been reported in a total of more than 1000 different human genes. Data on these mutations and their associated phenotypes have been collated and are available online through two major databases: Online Mendelian Inheritance in Man in Baltimore and the Human Gene Mutation Database in Cardiff. Since the non-randomness of mutation is determined largely by the local DNA sequence environment, the study of mutation may not only yield information on underlying mechanisms but also lead to the optimization of mutation search strategies. CONCLUSION: There is a high frequency of CG to TG or CA mutations in the human genome due to deamination of 5' methyl-cytosine. The second most common type of mutations in human disorders is short deletions or insertions of less than 20 nucleotides. PMID- 11216896 TI - Bridging the gap between molecular genetics and metabolic medicine: access to genetic information. AB - Thanks to the World Wide Web, most results of research in genetics are made available in public databases. At the present time there are resources on genetic diseases, genes and their location, mutations of already cloned genes and on laboratories performing the mutation analysis. The main resources on phenotypes are On-line Mendelian Inheritance in Man (OMIM), Pedbase, GeneClinics, London Dysmorphology Database (LDDB) and Orphanet. The main resources on human genes are, in addition to OMIM, the Genome Database, Genatlas and Genecard. There are also two major sequence databases. All of them can be queried using the OMIM number of the disease. Central databases of mutations, as well as locus specific databases have been created. Their list is maintained at the Human Genome Organisation mutation database initiative website. Several initiative have been taken to integrate all these data and help the clinician to find out quickly what he/she needs. The website of the National Center for Biotechnology Information is the best example of such an effort with sections on diseases, a genome guide, and locus links. Several databases of genetic testing resources have been established. GeneTests is an on-line genetics resource that contains a directory of North American laboratories providing testing for heritable disorders. Orphanet is a similar database on French services which is in the process of becoming a European database. CONCLUSION: Even if clinicians do not have as many services at their disposal as the molecular geneticists, various useful databases already exist and should no longer be ignored in practice. PMID- 11216897 TI - Mutation screening for prenatal and presymptomatic diagnosis: cystic fibrosis and haemochromatosis. AB - Hereditary haemochromatosis (HH) and cystic fibrosis (CF) are the most common autosomal recessively inherited disorders in Caucasian populations. In its typical form, CF manifests during the first years of life, while the mean age of onset of organ damage is 54 years in HH. Both disorders can be diagnosed presymptomatically utilising biochemical and/or genetic testing. Since approximately 90% of mid-European HH patients are homozygous for only one specific mutation (C282Y) in the candidate gene for HH, genetic testing is simple and sensitive in HH. In CF, molecular testing is currently hampered by the large number (more than 800) of mutations in the CF transmembrane conductance regulator gene. Several studies have been initiated to investigate the potential benefits and the best time and mode of presymptomatic testing for HH and CF. CONCLUSION: Mutation analysis is widely recommended for presymptomatic diagnosis of cystic fibrosis and hereditary haemochromatosis because of the presumed benefit, although several medical, ethical, social and technical questions warrant further investigations. Prenatal mutation testing is commonly performed for cystic fibrosis but not for hereditary haemochromatosis. Informed consent of tested individuals and the availability of genetic counselling is a prerequisite for any mutation screening approach in either disease. PMID- 11216898 TI - Population-based genetic screening for reproductive counseling: the Tay-Sachs disease model. AB - Since 1970, more than 1.4 million individuals worldwide have been screened voluntarily to determine if they are carriers of the mutant gene for Tay-Sachs Disease (TSD). Employing both enzymatic and molecular methods (for optimal sensitivity and specificity) more than 1400 couples have been identified to be at risk for TSD in their offspring, i.e., both parents heterozygotes. Through prenatal testing of more than 3200 pregnancies, births of over 600 infants with this uniformly fatal neurodegenerative disease have been prevented. In the United States and Canada, the incidence of TSD in the Jewish population has been reduced by more than 90%. More that 100 mutations in the hexosaminidase A gene (the TSD locus) have been identified to date. Some are associated with later onset or more chronic forms of neuronal storage disease. Two mutations cause a carrier-like "pseudo-deficiency" when enzymatic testing is used (false positives). A number of practical, social, and ethical complexities have been identified in this prototypic population-based effort. Educational and counseling components must be provided both before and after screening. Issues of privacy and confidentiality of test results must be addressed. In certain cultures insurability and employment may be involved. The public perception of the biomedical community as advocates for wide-scale testing and screening may be interpreted, in some systems, as conflicts of interest on the part of entrepreneurial scientists, clinicians, and institutions. CONCLUSION: Many new opportunities for population based screening will be evident in this era of genome-related discovery. Accordingly, some of the experiences with Tay-Sachs disease prevention may be instructive. PMID- 11216899 TI - The molecular basis of ornithine transcarbamylase deficiency. AB - The ornithine transcarbamylase (OTC) gene is located on the short arm of the X chromosome and encodes the second enzyme of the urea cycle. OTC deficiency is an X-linked disorder that causes hyperammonemia leading to brain damage, mental retardation and death. The clinical and biochemical phenotype is extremely variable and can only partially be explained by the genotype. We identified mutations in the OTC gene of more than 150 patients with OTC deficiency. The "neonatal onset" group of patients has mutations that abolish enzyme activity, whereas the "late onset group" shows partial enzyme deficiency to variable degree. Of the mutations, 60% are associated exclusively with acute neonatal hyperammonemic coma while the remaining cause "late onset" disease. Several symptomatic and asymptomatic adults have now been identified to have deleterious mutations in the OTC gene leading to predisposition to hyperammonemia. CONCLUSION: The enlarging clinical, biochemical and molecular spectrum observed in patients with ornithine transcarbamylase deficiency suggests that this disorder behaves like a single gene disorder at one end of the spectrum and as a multi-factorial disease at the other. PMID- 11216901 TI - Galactosaemia and allelic variation at the galactose-1-phosphate uridyltransferase gene: a complex relationship between genotype and phenotype. AB - More than 160 different base changes have been described at the galactose-1 phosphate uridyltransferase gene and most of these are associated with a disease phenotype. Q188R is the most common mutation in north European populations and those predominantly of European descent. K285N is much rarer but in some countries of east/central Europe it is the second most common mutation. In some populations of northern Europe these two mutations can be found on 70%-80% of mutant chromosomes. Both mutations appear to be associated with a complete loss in enzyme activity and thus, a more severe biochemical phenotype. A single amino acid substitution, N314D, is found on both Duarte 1 and Duarte 2 alleles. Additional base changes that are different on each distinguish D1 from D2 alleles. Whether the differences in galactose-1-phosphate uridyltransferase enzyme activities are associated with the additional molecular changes that distinguish D1 and D2 alleles remains unclear. S135L is found almost exclusively in galactosaemic individuals of African origin. Despite early diagnosis and treatment and adherence to a lactose free diet neurological complications, poor growth and reduced fertility are frequently observed in affected individuals. CONCLUSION: Allelic variation at the galactose-1-phosphate uridyltransferase gene undoubtedly plays a role in defining the biochemical and clinical phenotype. However, clinical galactosaemia is a complex trait in which multiple developmental and metabolic pathways are involved. Ultimately the phenotype is beyond the control of the single gene itself. PMID- 11216900 TI - Inherited ion channel disorders. AB - The inherited ion channel disorders (channelopathies) are a group of disorders caused by mutations in genes encoding ion channels. Ion channel disorders can affect any tissue, but the majority affect skeletal muscle or the central nervous system. These disorders include skeletal muscle sodium channelopathies causing hyperkalaemic periodic paralysis, paramyotonia congenita and potassium-aggravated myotonia. Skeletal muscle calcium channelopathies can cause hypokalaemic periodic paralysis, malignant hyperthermia and central core disease. Skeletal muscle chloride channelopathies can cause Thomsen and Becker myotonia. A neuronal sodium channelopathy causes the generalised epilepsy febrile seizures plus syndrome. Neuronal potassium channelopathies can cause familial benign neonatal convulsions and episodic ataxia type 1. Finally, neuronal calcium channelopathies can cause episodic ataxia type 2, familial hemiplegic migraine and spinocerebellar ataxia type 6. CONCLUSION: The clinical features, aetiology and pathogenesis of inherited voltage-gated ion channel disorders affecting muscle and the central nervous system are reviewed here. PMID- 11216902 TI - Genetic determinants of hyperhomocysteinaemia: the roles of cystathionine beta synthase and 5,10-methylenetetrahydrofolate reductase. AB - Over the last decade mild hyperhomocysteinaemia has widely been recognised as a new risk factor for arteriosclerosis and thrombosis. Main regulating enzymes of homocysteine (Hcy) metabolism are cystathionine beta-synthase (CBS), methionine synthase and methylenetetrahydrofolate reductase (MTHFR). Early studies on patients with vascular disease described elevated Hcy concentrations after methionine loading and decreased CBS activity, resembling heterozygotes for CBS deficiency. Therefore, heterozygosity for CBS deficiency was proposed as the main cause of mild hyperhomocysteinaemia. However, more recent enzymatic and molecular genetic studies have demonstrated that heterozygosity for CBS deficiency is not or only a very minor cause of mild hyperhomocysteinaemia in vascular disease. We discovered two common genetic causes of mild hyperhomocysteinaemia, the 677C > T and the 1298A > C mutations in the coding region of MTHFR. The 677C > T mutation causes reduced enzyme activity with thermolabile protein properties, elevated Hcy and low-normal or decreased plasma folate levels. The 1298A > C mutation relates also to decreased enzyme activity, but not to thermolabile protein, and Hcy and folate levels are not influenced. However, compound heterozygosity for these two mutations, i.e. individuals with the 677CT/1298AC genotype, have elevated Hcy and decreased plasma folate levels. Gene-enviroment interactions between 677C > T and folate is demonstrated in individuals with the 677TT genotype. Those with low normal folate have elevated Hcy, whereas those with high-normal folate have normal Hcy concentrations. The elevated Hcy levels due to these mutations can be normalised by administration of folate, but whether folate reduces the risk of cardiovascular disease remains to be established. CONCLUSION: Heterozygosity for cystathionine beta-synthase deficiency is a minor cause of hyperhomocysteinaemia. The current data on mutations in the methylenetetrahydrofolate reductase gene do not tell us whether elevated plasma homocysteine plays a causal role in vascular disease. Low cellular vitamin status may be a possible cause and homocysteine may just be a marker for this situation. PMID- 11216903 TI - Prevalent mutations in fatty acid oxidation disorders: diagnostic considerations. AB - The mutational spectrum in a given disease-associated gene is often comprised of a large number of different mutations, of which a single or a few are present in a large proportion of diseased individuals. Such prevalent mutations are known in four genes of the fatty acid oxidation: the medium-chain acyl-CoA dehydrogenase (MCAD) gene; the short-chain acyl-CoA dehydrogenase (SCAD) gene; the long-chain 3 hydroxy acyl-CoA dehydrogenase (LCHAD) gene and the carnitine-palmitoyl-CoA transferase II (CPT II) gene. In MCAD deficiency the analysis confirms the conventional wisdom that individuals carrying the prevalent 985A > G mutation are at risk of developing life-threatening attacks. In SCAD/ethylmalonic aciduria, on the other hand, the presence of the prevalent susceptibility variations, 625A and 511T, in the SCAD gene seems to require additional genetic and cellular factors to be present in order to result in a phenotype. For the prevalent mutations in the LCHAD and CPT II genes further data are needed to evaluate the penetrance and risk of manifest disease when carrying these mutations. CONCLUSION: Assessment of the prevalence of a prevalent mutation in the mutation spectrum of the disease in question and determination of the carrier frequency in the general population may help in elucidating the penetrance of the genotype. This is exemplified in disorders of mitochondrial fatty acid oxidation. PMID- 11216904 TI - Mitochondrial DNA disorders. AB - Over 100 pathogenic point mutations and 200 deletions, insertions, and rearrangements have been identified since the first mitochondrial DNA mutations were described in 1988. About 60% of the point mutations affect mitochondrial tRNAs, 35% affect polypeptide subunits of the respiratory chain, and 5% affect mitochondrial ribosomal RNAs. The clinical phenotypes of mitochondrial tRNA disease span the spectrum of all known oxidative phosphorylation disorders and include MELAS, MERRF, Leigh syndrome, PEO, deafness, diabetes, sideroblastic anemia, myoclonus, skeletal myopathy, cardiomyopathy, and renal tubular acidosis. Mutations in respiratory chain proteins encoded by mtDNA result in phenotypes ranging from exercise intolerance to blindness, ataxia, dystonia, dementia, and Leigh syndrome. CONCLUSION: The primary disorders of oxidative phosphorylation are commonly associated with a delayed age of onset, organ selectivity, and an episodic, progressive course. Organ-specific, non-ATP related functions of mitochondria are discussed as important considerations in evaluating the pathogenesis of mitochondrial disease. PMID- 11216905 TI - Nuclear genes and oxidative phosphorylation disorders: a review. AB - Knowledge concerning the approximately 70 human nuclear genes creating the essential building-blocks of the five multi-protein subunit complexes of the oxidative phosphorylation (OXPHOS) system has been expanded greatly in the past few years. However, knowledge concerning the numerous human genes involved in the regulation of transcription, translation, post-translational modification, mitochondrial signalling, import, quality control, folding and assembly of the OXPHOS system is still rather scanty. It may be expected that this scenario, by the application of direct (candidate gene identification by comparison between known genes in lower species and the human expressed sequence tag database) and indirect genetic strategies (the chromosome transfer technique, linkage analysis and positional cloning) will rapidly change. By now, a limited number of structural and non-structural nuclear gene defects have been found. CONCLUSION: This review summarises the state of our current knowledge of nuclear gene mutations in oxidative phosphorylation disorders. PMID- 11216906 TI - Hereditary deafness: lessons for developmental studies and genetic diagnosis. AB - Hereditary deafness is highly heterogeneous genetically, with over 100 loci so far identified. Routine diagnostic mutation screening can be done only when a candidate gene has been identified, and preferably a candidate mutation. For syndromic forms of hearing loss it is often possible to predict the gene involved. Non-syndromic loss is much more intractable to diagnostic mutation screening because of the extensive locus heterogeneity. However, mutations in the connexin 26 (GJB2) gene and the mitochondrial m. 1555A > G mutation are sufficiently frequent in some populations to justify mutation testing. Identifying the genes mutated in syndromic hearing loss can help delineate developmental pathways. CONCLUSION: The example of Waardenburg syndrome is used to illustrate how unravelling developmental pathways can be more complicated than defining metabolic pathways through biochemical defects. Developmental genes tend to be organised into networks rather than linear pathways, and transcription factors act in a combinatorial manner. This makes developmental pathways harder to unravel genetically than metabolic pathways. PMID- 11216907 TI - Organelle disease: peroxisomal disorders. AB - Peroxisomes are virtually ubiquitous organelles involved in numerous catabolic and anabolic pathways. Interest in peroxisomes stems from an expanding group of genetic diseases in which there is either deficiency of a specific peroxisomal function (single protein defects) or failure to assemble the organelle resulting in defects of multiple peroxisome functions (peroxisome biogenesis disorders). The paradigm for the former is X-linked adrenoleukodystrophy caused by mutations in the adrenoleukodystrophy gene and, for the latter, Zellweger syndrome caused by mutations in peroxin genes. CONCLUSION: The identification and functional characterisation of the peroxisomal disease genes is proceeding at rapid pace helped immeasurably by work in various yeast model systems. The ultimate goal is to elucidate how the encoded proteins produce normal appearing and functioning peroxisomes. The achievement of this goal will lead to a better understanding of peroxisomal disorders, their pathogenesis and treatment. PMID- 11216908 TI - What has happened to gene therapy? AB - Trials have demonstrated the feasibility of gene therapy in correcting the gene defect in monogenic disorders such as severe combined immune deficiency and cystic fibrosis, but there are still obstacles and ethical issues to overcome. CONCLUSION: With appropriate research, better delivery strategies and adherence to good standard clinical research and practice, gene therapy research will lead to clinical implementation in monogenic and multifactorial disorders including cancer, neurodegenerative disorders and vascular disease. PMID- 11216909 TI - Mutation analysis in metabolic (and other genetic) disease: how soon, how useful. PMID- 11216910 TI - The potent antitumor effects of combined p16 gene and GM-CSF gene therapy through efficient induction of antitumor immunity. AB - PURPOSE: Tumor suppressor gene therapy and cytokine gene therapy have limited antitumor effects when used alone. Thus, in the present study, we investigated the antitumor potentials of the combined transfer of the p16 tumor suppressor gene and the murine granulocyte-macrophage colony-stimulating factor (GM-CSF) gene. METHODS: The adenovirus-harboring p16 gene (Adp16) and adenovirus-harboring GM-CSF (AdGMCSF) gene were utilized for the treatment of established tumors in vivo. The mice were inoculated s.c. with Renca renal carcinoma cells and 3 days later received an intratumoral injection of Adp16 in combination with AdGMCSF. RESULTS: The results demonstrated that tumor-bearing mice treated with Adp16 and Ad-GMCSF showed more potent inhibition of tumor growth and a prolonged survival period than mice treated with Adp16. AdGMCSF, adenovirus-expressing beta galactosidase or PBS (P<0.01). Treatments of the mice with Adp16 alone or AdGMCSF alone also showed obvious antitumor effects as compared with those mice treated with PBS (P<0.05). After combined p16 and AdGMCSF gene therapy, the expression of H2Kd and Fas molecules on freshly isolated tumor cells increased markedly, and more CD(4)+ T cells and CD(8)+ T cells infiltrated in the tumor sites. The cytotoxicity of natural killer cells and specific cytotoxic T lymphocytes increased more significantly after the combined therapy. CONCLUSIONS: Our results demonstrated that combination p16 gene and GM-CSF gene therapy could inhibit the growth of established tumors in mice more significantly through efficient induction of antitumor immunity. PMID- 11216911 TI - Allelic loss of cyclophilin 40, an estrogen receptor-associated immunophilin, in breast carcinomas. AB - PURPOSE: Cyclophilin 40 (CyP40) is an estrogen receptor-associated protein which appears to modify receptor function. The aim of this study was to determine the extent of allelic loss at the CyP40 locus in a panel of breast carcinomas using a newly characterized microsatellite marker located upstream of the CyP40 gene and then to correlate this with losses at chromosomal sites for cancer-associated genes. METHODS: Allelic loss at CyP40 was determined from patients' matched tumor and normal breast tissue using Genescan 672 software analysis of fluorescently labeled, PAGE-separated PCR products incorporating the marker. For each patient, allelic loss at CyP40 was then assessed and compared with losses at markers for various cancer-associated genes. RESULTS: Allelic loss was detected in 30% of breast carcinomas from patients heterozygous for the CyP40 marker. All carcinomas demonstrating allelic loss were grade II or III invasive ductal carcinomas and generally showed multiple losses at other sites near known cancer-associated genes. CONCLUSIONS: The polymorphic marker which we characterized was useful in determining allelic loss at the CyP40 locus in breast cancer patients and when applied in these studies in conjunction with various cancer-associated gene markers, suggests that deletions in the region of the CyP40 gene might be a late event in breast tumor progression. PMID- 11216912 TI - Computed direct magnification radiography of bone tumors. AB - The purpose of this study was to assess the diagnostic performance of computed direct magnification radiography in diagnosing bone tumors as compared with conventional radiography. Ninety-one patients with primary bone tumors and tumor like lesions were radiographed with conventional and magnification techniques. All radiographs were analyzed by one orthopedic surgeon and two radiologists and the findings were correlated with histopathology. Two microfocal X-ray units were used for computed direct magnification radiography with a focal spot size of 20 130 microm. Using magnification versus conventional radiography, the diagnosis of benign and malignant lesions as well as the individual tumor diagnosis was obtained with higher accuracy (85% versus 71% and 69% versus 51%, respectively, P<0.01). Margins of destruction, periosteal reactions, and matrix patterns were evaluated with higher accuracy by all observers (P<0.01). We conclude that computed direct magnification radiography may improve evaluation and diagnosis of bone tumors. PMID- 11216913 TI - Pleural mesothelioma associated with indoor pollution of asbestos. AB - This case report concerns a 46-year-old woman, dying from histologically confirmed diffuse malignant mesothelioma after asbestos exposure, which was only caused by indoor pollution from crocidolite-containing spray asbestos in building materials. There was no other known occupational or environmental asbestos exposure during her life. The lung tissue fibre analysis by light microscopy showed significantly increased concentrations of ferruginous bodies (3162 FB per gram of wet lung tissue). By use of scanning transmission electron microscopy, clearly increased concentrations of amphibole fibres (8.6 x 10(6) fibres longer than 1 microm and 0.6 x 10(6) fibres longer than > or =5 microm per gram dry tissue), mainly classified as crocidolite, were observed. The disease was attributed to indoor exposure to sprayed asbestos, which occurred during her work as a decorator in the studio of a warehouse. PMID- 11216914 TI - Pegylated doxorubicin for primary cutaneous T-cell lymphoma: a report on ten patients with follow-up. AB - PURPOSE: Pegylated liposomal doxorubicin (PEG-DOXO) was found to be effective in primary cutaneous T-cell lymphomas (CTCL). The present observation reports on follow-up and relapse-free interval in patients with CTCL. METHODS: Ten patients (one female, nine male) aged 50-78 years (mean 66.7 years) with relapsing or recalcitrant CTCL, stage I b (n = 3), II a (2), II b (3), IV a (1), and IV b (1) were treated with PEG-DOXO 20 mg m(-2) once a month with an upper limit of 400 mg or eight infusions to induce a clinical response. There was one drop out after a single infusion because of a capillary leak syndrome. RESULTS: In nine patients with PEG-DOXO the best response was a complete response (CR) in five patients and a partial response (PR) in four patients. The final outcome was CR in six, PR in two, stable disease (SD) in one, and progressive disease (PD) in another patient. The overall response rate (CR + PR) was 80% (of ten patients). The follow-up was 2-22 months (mean 12.8+/-7.1 months). The overall survival was calculated as 19.8+/-7.4 months with eight out of ten patients still alive. Response duration was 15.2+/-3.9 months, disease-free survival 13.3+/-6.1 months, event-free survival 16.7+/-9.0 months, and progression-free survival 18.2+/-6.5 months. Four patients (stage I b and II b) achieved 12-19 months of disease-free survival. The follow-up after the first course with PEG- DOXO was 2-22 months (mean 12.8+/-7.1 months). The survival rate after 12 months of follow-up was 80% (n = 5). One patient free of relapse died after 12 months because of pulmonary embolism not related to disease or treatment. Another patient died 1 month after a second course of PEG-DOXO in an advanced tumor stage of CTCL. The most frequent side effects of treatment were anemia and lymphopenia without the need of supportive treatment or dose-reduction. Only one patient developed toxicity of grade 4 (anemia). CONCLUSIONS: These results indicate that patients with relapsing or recalcitrant CTCL can achieve an 80% response rate with PEG-DOXO and long-term remissions. PMID- 11216915 TI - CYP19 gene polymorphism in endometrial cancer patients. AB - PURPOSE: Initiation/promotion of endometrial cancer is known to be associated with estrogenic influence. Therefore, it is possible that some allelic polymorphisms of the genes involved in steroidogenesis or steroid metabolism contribute to endometrial cancer susceptibility. METHODS: Here, we compared CYP19 (aromatase) gene polymorphism in 85 endometrial cancer patients and in 110 non affected women. RESULTS: The genotypes containing the longest alleles (A6 and A7) of CYP19 were found to be over-represented in patients as compared to controls. In addition, these genotypes demonstrated a tendency to be associated with increased concentrations of estradiol and testosterone in postmenopausal patients. CONCLUSIONS: Thus, CYP19 polymorphism might be one of the genetic risk factors for endometrial cancer development. PMID- 11216916 TI - Transition from suspension to adherent growth is accompanied by tissue factor expression and matrix metalloproteinase secretion in a small cell lung cancer cell line. AB - Small cell lung cancer (SCLC) is a very malignant tumor known to grow aggressively and to metastasize early. It is well established that metastasis generally involves both tumor cell adhesion and proteolytic degradation of the extracellular matrix. However, SCLC cells cultured in vitro, such as the classic SCLC cell line NCI-H69, grow in floating aggregates and express only negligible proteolytic activity. In this report, we show that NCI-H69 cells can be selected for adherent growth. In contrast to parental suspension cells, the adherent cells were found to express tissue factor as well as gelatinolytic activity, attributable to matrix metalloproteinases 2 and 9. Such a switch of tumor cell characteristics, if it could occur in SCLC patients, might add to the understanding of the steps involved in the spreading of this highly metastatic type of lung cancer. PMID- 11216917 TI - Epidemiological and molecular aspects of ovarian cancer risk. AB - In Western and Northern Europe, as well as in the United States, ovarian cancer represents the third most frequent cancer of the female genital tract with an estimated 191,000 newly diagnosed cases per year worldwide. Due to its insidious onset, the disease is diagnosed in 70% of cases in an advanced stage. Consequently, ovarian cancer is the fifth leading cause of cancer-related deaths in women. Epidemiological and molecular studies reviewed here have identified demographic, geographic, molecular, genetic, endocrine, dietary, and environmental factors, which affect the risk of developing ovarian cancer: ethnic background, tumor suppressor gene mutations in the germline, positive family history, number of full-term pregnancies [odds ratio (OR): 0.17; 95% confidence interval (CI): 0.05-0.54], time spent breast feeding, oral contraceptive use [OR: 0.23; 95% CI: 0.1-0.50], unexplained infertility (OR: 2.64; 95% CI: 1.10-6.35), tubal ligation and prior hysterectomy (OR: 0.5; 95% CI: 0.2-0.9), dietary factors and obesity (OR: 1.7; 95% CI: 1.1-2.8). This knowledge provides the objective basis for an individual risk assessment for women, which should lead to sophisticated counseling and prevention. It should also help to individualize the therapeutic approach in the event that disease is diagnosed. PMID- 11216918 TI - Molecular genetics in acute and chronic leukemias. AB - The application of molecular biological techniques in malignant hematologic diseases, particularly leukemias, has led to a rapid increase in knowledge and a deeper insight into the pathobiology of these diseases. Leukemia is a very heterogeneous disease on the molecular level. Clonal chromosomal abnormalities can be found in the vast majority of cases. A broader understanding of the underlying molecular changes has enabled the development of risk-adapted therapy regimens with improved outcome. One example is the application of molecular genetic techniques for detecting small numbers of leukemia cells after therapy ("minimal residual disease"). This allows the early preclinical recognition and prevention of relapse. This study gives a short overview of the current status of molecular genetics in human leukemias and its implications for the therapy and prognosis of these diseases. The following topics are covered: generation of oncogenic fusion genes or dysregulation of protooncogenes by chromosomal translocations, detection of minimal residual disease based on clonally rearranged immunoglobulin or T-cell receptor genes or on leukemia-specific fusion genes, monitoring bone marrow chimerism after allogeneic transplantation by molecular genetic techniques, and the role of oncogenic herpesviruses and retroviruses in human hematologic malignancies. PMID- 11216919 TI - Chemotherapy for malignant brain tumors of astrocytic and oligodendroglial lineage. AB - To date, surgery and irradiation remain the standard therapies for anaplastic astrocytoma (AA, WHO grade III) and glioblastoma multiforme (GBM, WHO grade IV). Due to infiltrative tumor growth a complete surgical resection is never achieved and more than 90% of the tumors will recur within 2 cm of the primary tumor location. Postoperative radiotherapy prolongs survival but is not curative and prognosis remains poor with only a few patients being alive 2 years after diagnosis. Over the past decades multiple trials dealt with the question of whether chemotherapy (CT) may influence the outcome of malignant brain tumor patients. In general, the results have been disappointing with one exception: chemosensitivity and prolonged survival after CT have been demonstrated for tumors of oligodendrogial lineage. Drugs showing some activity in malignant brain tumors and therapeutic concepts will be discussed. PMID- 11216920 TI - A low dose of ionizing radiation increases luminal release of intestinal peptidases in rats. AB - PURPOSE: Mucosal inflammation in the small intestine is a potentially hazardous side effect of abdominal irradiation. In an effort to develop a quantitative method of evaluating mucosal damage, the luminal release of brush border enzymes in response to ionizing radiation was examined using two investigational strategies. METHODS: First, a 20 cm segment of the proximal jejunum was perfused in situ and enzymatic activities within the perfusates were evaluated. In a second approach, enzymatic activities were directly evaluated in isolated brush border membranes from the jejunal mucosa. RESULTS: Most of the peptidase activities measured were increased in the perfusates 1 day after irradiation and had returned to control levels at 4 days. In the brush border membranes, some enzyme activities decreased at 1 day and were, with the exception of leucineaminopeptidase (LAP), similar to control levels at 4 days. CONCLUSIONS: LAP is more strongly affected by radiation than the transmembranously bounded enzymes. PMID- 11216921 TI - Tuberculosis case fatality rates in high HIV prevalence populations in sub Saharan Africa. AB - BACKGROUND: Tuberculosis is a leading cause worldwide of morbidity and mortality among HIV-infected people. The HIV era has seen a dramatic increase of the tuberculosis case fatality rate (CFR) in high HIV prevalence populations. Providing care for HIV-infected people must include measures to tackle this high tuberculosis CFR. AIMS: To analyse the extent of the increased tuberculosis CFR in high HIV prevalence populations in sub-Saharan Africa, the reasons for this increase and the causes of death, in order to identify possible ways of tackling this problem. METHODS: References were obtained by searching the MEDLINE on 'tuberculosis', 'HIV infection', and 'mortality' (MesH or textword). In addition, available data from National Tuberculosis Programme reports were reviewed. FINDINGS: Tuberculosis CFR is closely linked to HIV prevalence. Limited autopsy data suggest that death from HIV-related diseases other than tuberculosis is probably the main reason for the increased CFR in HIV-infected tuberculosis patients. Among HIV-infected tuberculosis patients, the higher tuberculosis CFR in sputum smear-negative and extrapulmonary than in sputum smear-positive tuberculosis cases can also be attributed to misdiagnosis of HIV-related diseases as tuberculosis. The adverse effect of the HIV/AIDS epidemic on general health service performance probably accounts for the higher tuberculosis CFR among HIV negative tuberculosis patients in high prevalence populations than that in low HIV-prevalence populations. CONCLUSION: Tackling the problem of the increased tuberculosis CFR in high HIV prevalence populations requires collaboration between tuberculosis control and HIV/AIDS programmes in implementing measures such as improved health services, tuberculosis and HIV control services, preventive treatment for HIV-related diseases and anti-HIV treatment. PMID- 11216922 TI - Should physicians withhold highly active antiretroviral therapies from HIV-AIDS patients who are thought to be poorly adherent to treatment? PMID- 11216923 TI - Chemokine/CD4 receptor density ratios correlate with HIV replication in lymph node and peripheral blood of HIV-infected individuals. AB - OBJECTIVES: Lymphoid tissue is a major reservoir for virus replication in HIV infected subjects. The relationship of CCR5 and CXCR4 coreceptor density and HIV replication in peripheral blood mononuclear cells (PBMC) and lymph node (LN) mononuclear cells (LNMC) of HIV-infected subjects was examined. METHODS: PBMC and cervical LNMC from 12 HIV-infected patients were examined for virological and immunological parameters including chemokine receptor density, HIV plasma and cellular viral load, coreceptor usage and CD38/HLA-DR expression. RESULTS: The number of CCR5 and CXCR4 molecules on CD4 lymphocytes in the LN were significantly higher than in PBMC. In contrast the number of CD4 molecules/CD4 T cell was higher in PBMC than in LNMC. The CXCR4/CD4 and CCR5/CD4 ratios in the LN were significantly higher than in the PBMC. This was associated with a cellular viral load in the LN that was approximately 110-fold higher than in PBMC. The absolute number of coreceptor molecules per cell did not correlate with the viral load. However, the CCR5/CD4 and CXCR4/CD4 ratios in the LN positively correlated with HIV cellular and plasma RNA. Characterization of the viral isolates suggested an association between clinical isolates using a distinct coreceptor and the upregulation of the corresponding chemokine receptor. CONCLUSIONS: The ratios of chemokine receptors to CD4 molecules in CD4 T cells from LN is higher than in PBMC and may account for the relative difference in cellular viral load in these compartments. Additionally, the coreceptor/CD4 ratios, particularly in the lymphoid tissue, were highly related to HIV replication. PMID- 11216924 TI - Novel mutations identified using a comprehensive CCR5-denaturing gradient gel electrophoresis assay. AB - BACKGROUND: Most mutations detected for the gene for CC chemokine receptor 5 (CCR5) are either relatively specific to different population groups or rarely observed in Africans. OBJECTIVES: To develop a comprehensive mutation detection assay for the entire coding region of CCR5 and to identify novel mutations that may play a role in genetic susceptibility to HIV-1 infection, within the diverse South African population. DESIGN: The study cohort consisted of 103 HIV seropositive patients and 146 HIV-seronegative controls of predominantly African descent. METHODS: A mutation detection assay for the entire coding region of CCR5 was designed; this included amplification of part of the coding region of CCR2. The assay was based on denaturing gradient gel electrophoresis (DGGE) and allowed the complete analysis of samples from 10 individuals per denaturing gel. RESULTS: The use of the CCR5-DGGE assay led to the identification of seven novel and six previously reported mutations. All novel mutations, including a common polymorphism at codon 35, occurred exclusively in non-Caucasians, indicating possible African origin. CONCLUSION: A comprehensive DGGE mutation detection assay has been developed for the entire coding region of CCR5. Application of this assay resulted in the identification of novel CCR5 mutations, which may have a significant effect on the normal functioning of CCR5 and thus contribute to host variability and susceptibility to HIV-1 infection and/or progression to AIDS within this population. PMID- 11216925 TI - Protease inhibitor-resistant HIV-1 from patients with preserved CD4 cell counts is cytopathic in activated CD4 T lymphocytes. AB - OBJECTIVE: To evaluate CD4 T-cell cytopathicity of protease inhibitor (PI) resistant isolates from patients with preserved CD4 cell counts after long-term virologic failure. METHODS: PI-resistant primary isolates from 14 patients with stable or increasing CD4 T-cell counts despite long-term virologic failure during continuous combination therapy were examined. Replication and cytopathicity were assessed in activated peripheral blood mononuclear cell cultures in the presence and absence of PI using titered stocks of primary HIV-1 isolates and during initial viral isolation. Also studied were PI-sensitive isolates from four of these patients after therapy discontinuation and reversion to PI-sensitive virus and from seven antiretroviral drug-naive patients. Coreceptor use, syncytia inducing (SI) phenotype and protease sequences were determined by standard methods. RESULTS: All isolates obtained during continued therapy showed genetic markers of PI resistance and decreased phenotypic susceptibility. PI-resistant SI isolates were highly to moderately cytopathic whereas non-syncytia-inducing isolates were moderately to weakly cytopathic. PI-susceptible and PI-resistant isolates obtained after discontinuation of therapy were equally cytopathic at similar replication levels. The cytopathicity of PI-resistant isolates was not altered by PI and was similar to that of isolates from untreated subjects. CONCLUSIONS: Primary isolates from patients showing virologic rebound without net CD4 T-cell loss during continued therapy are as cytopathic as PI-sensitive isolates with equivalent input infectious titer. As with PI-sensitive isolates, cytopathicity of PI-resistant viruses was determined primarily by coreceptor preference. These results suggest that the sustained immunologic response observed after failure of PI-containing regimens is not due to the emergence of PI-resistant strains that are intrinsically less cytopathic for activated peripheral CD4 lymphocytes. PMID- 11216926 TI - Reasons for modification and discontinuation of antiretrovirals: results from a single treatment centre. AB - OBJECTIVE: To describe the reasons for, and factors associated with, modification and discontinuation of highly active antiretroviral therapy (HAART) regimens at a single clinic. SUBJECTS: A total of 556 patients who started HAART at the Royal Free Hospital were included in analyses. Modification was defined as stopping or switching any antiretrovirals in the regimen, whereas discontinuation was defined as the simultaneous stopping of all antiretrovirals included in the initial regimen. Reasons were classified as immunological/virological failure (IVF) and toxicities and patient choice/poor compliance (TPC). RESULTS: The median CD4 count at starting HAART was 171 x 10(6) cells/l and viral load 5.07 log copies/ml. During a median follow-up of 14.2 months, 247 patients (44.4%) modified their HAART regimen, 72 due to IVF (29.1%) and 159 due to TPC (64.4%) and a total of 148 patients (26.6%) discontinued HAART. Older patients were less likely to modify HAART [relative hazard (RH), 0.73 per 10 years; P = 0.0008], as were previously treatment-naive patients (RH, 0.65; P = 0.0050), those in a clinical trial (RH, 0.64; P = 0.027) and those who started nelfinavir (RH, 0.57; P = 0.035). Patients who started with four or more drugs (RH, 2.21, P < 0.0001), who included ritonavir in the initial regimen (RH, 1.41; P = 0.035) or who had higher viral loads during follow-up (RH per log increase, 1.51; P < 0.0001) were more likely to modify HAART. CONCLUSIONS: There was a high rate of modification and discontinuation of HAART regimens in the first 12 months, particularly due to toxicities, patient choice or poor compliance. PMID- 11216927 TI - Outcome of patients with HIV-1-related cognitive impairment on highly active antiretroviral therapy. AB - OBJECTIVE: To examine the impact of highly active antiretroviral therapy (HAART) on the outcome of HIV-1-related cognitive impairments using a neuropsychological (NP) battery to assess separately the psychomotor, executive function and memory fields. DESIGN: A longitudinal study of HIV-1-infected patients based on serial NP tests in a Paris University Hospital. METHODS: A group of 91 HIV-1-infected patients, of whom 47 were already taking HAART at their first NP examination, were initially categorized as cognitively impaired (n = 53) or non-impaired (n = 38) and underwent one to six serial NP batteries (mean follow-up 12.3+/-8.3 months). Generalized estimating equations (GEE) were used to evaluate performance in a given NP test according to the number of days on HAART. RESULTS: Despite a 25% mortality rate among patients who had cognitive impairment at their first NP examination, GEE showed a positive relationship between the duration of HAART and cognitive performance. Performance in psychomotor tests (e.g. Purdue Pegboard dominant hand) improved continuously during the study period, while memory test performance (e.g. Grober and Buschke free recall) tended to reach a plateau. CONCLUSIONS: HAART improves subcortical cognitive functions during the first year of treatment. Distinct neuropathological mechanisms appear to underlie psychomotor and memory dysfunctions in AIDS. PMID- 11216928 TI - The use of and response to second-line protease inhibitor regimens: results from the EuroSIDA study. AB - OBJECTIVE: To describe the use of second line protease-inhibitor (PI) regimens across Europe and to determine factors associated with virological and immunological response. DESIGN: Analysis of data from 984 patients with a median follow-up of 21 months enrolled in EuroSIDA. Patients started their second PI containing regimen at least 16 weeks after starting the first PI-containing regimen and with viral load > 1000 copies/ml. METHODS: Virological response was defined as a viral load < 500 copies/ml and immunological response as an increase of 50 x 10(6)/l or more in CD4 lymphocyte count. RESULTS: The median CD4 cell count at starting the second PI was 171 x 10(6) cells/l; viral load was 4.45 log copies/ml. As a second PI regimen, 45% were using a dual PI, while of those on one PI, indinavir (42%) and nelfinavir (34%) were most common. In multivariate Cox models, a higher viral load at starting the second PI [relative hazard (RH), 0.67 per 1 log higher; 95% confidence interval (CI), 0.58-0.77; P < 0.0001) and a lower CD4 cell count (RH, 1.15 per 50% higher; 95% CI, 1.06-1.26; P = 0.0014) were associated with a reduced probability of virological response. Those who had achieved viral suppression on the first PI-regimen were more likely to respond to the second (RH, 1.65; 95% CI, 1.30-2.10; P < 0.0001) as were those who added one or two new nucleosides to their second PI. CONCLUSIONS: Patients who initiate a second PI regimen at lower viral load, higher CD4 cell count or who added new nucleosides tended to be more likely to achieve a viral load < 500 copies/ml. The roles of cross-resistance and adherence in response to second-line regimens needs further investigation. PMID- 11216929 TI - Atovaquone suspension for treatment of Pneumocystis carinii pneumonia in HIV infected patients. AB - OBJECTIVE: To describe clinical experience with atovaquone suspension for the treatment of Pneumocystis carinii pneumonia (PCP) in HIV-infected patients. DESIGN: A retrospective chart review. METHODS: The medical records of 54 HIV infected patients with PCP treated with atovaquone were examined. The outcomes of 34 patients treated with atovaquone suspension (750 mg twice a day) were compared with those of 20 patients treated with atovaquone tablets (750 mg three times a day). RESULTS: The proportion of patients successfully treated was similar with the suspension (74%) and tablet (70%) formulations of atovaquone. The proportion of patients with an inadequate response to therapy was lower for patients treated with atovaquone suspension (15%) than tablets (30%). Both formulations were well tolerated. CONCLUSION: Atovaquone suspension is effective and well tolerated for the treatment of PCP. PMID- 11216930 TI - Long-term effect of preventive therapy for tuberculosis in a cohort of HIV infected Zambian adults. AB - OBJECTIVE: To determine the long-term effect of preventive therapy (PT) for tuberculosis on the rates of tuberculosis, mortality and HIV progression. METHODS: In a randomized controlled trial, 1053 HIV-positive Zambian adults received isoniazid (H) for 6 months, rifampicin plus pyrazinamide (RZ) for 3 months, or a placebo. CD4 percentage, neopterin, absolute lymphocyte count and haemoglobin were measured from enrolment (absolute CD4 cell counts from 12 months after enrolment). Because PT reduced the incidence of tuberculosis, eligible placebo subjects were offered H. Here, tuberculosis and mortality rates are compared in the three original arms (intention to treat) using data beyond the end of the trial (average follow-up 3 years; maximum 7 years). RESULTS: There were 102 cases of tuberculosis and 281 deaths (rates 3.6 and 9.0/100 person years, respectively). There was no significant difference between the tuberculosis rates in the H and RZ groups at any time. The effect of H/RZ on tuberculosis diminished over time (P = 0.011) but the cumulative risk of tuberculosis in the first 2.5 years was significantly lower in the H/RZ group than the placebo group (rate ratio 0.55; 95% confidence interval 0.32-0.93; P = 0.028). There was no significant effect of PT on mortality or progression markers. Tuberculosis was associated with an increased mortality (adjusted rate ratio 1.96; 95% confidence interval 1.21-3.18; P = 0.006). CONCLUSIONS: Both PT regimens protect against tuberculosis for at least 2.5 years but appear to have no effect on HIV progression or mortality. These results may be used in cost effectiveness models of PT. PMID- 11216931 TI - Herpes zoster and HIV-1 infection in a rural Ugandan cohort. AB - OBJECTIVE: To compare the rates and clinical features of herpes zoster in HIV positive and HIV-negative individuals in a cohort in rural Uganda; to report the incidence of herpes zoster in the HIV-positive group in relation to seroconversion and CD4 cell counts and to determine whether it is indicative of a more rapid progression to death. DESIGN: A prospective population-based cohort. METHODS: The cohort comprised 107 prevalent and 144 incident (with documented dates of seroconversion) participants with HIV infection and 231 HIV-negative controls who were reviewed routinely every 3 months. RESULTS: The mean rate of herpes zoster was 53.6/1000 person-years in HIV-positive and 4.4 in HIV-negative participants. The cumulative incidence of a first episode of herpes zoster was 7.6% at 2 years, 12.6% at 4 years and 24.0% at 6 years after seroconversion; the incidence rate was 35.6/1000 person-years. There was no evidence of a significant effect of age, gender, period from seroconversion or CD4 cell count on this incidence rate. Herpes zoster was an indicator of HIV-1 infection in this population but not an indicator of more rapid progression to death after adjusting for CD4 cell count and age. CONCLUSIONS: The rates, including the cumulative incidence after seroconversion and the clinical presentation of herpes zoster, were similar to those reported from industrialized countries. Although an indicator of HIV-1 infection in this population, herpes zoster was unrelated to CD4 cell count or period from seroconversion and did not lead to a faster disease progression. PMID- 11216932 TI - Lipodystrophy-associated morphological, cholesterol and triglyceride abnormalities in a population-based HIV/AIDS treatment database. AB - OBJECTIVE: To provide population-based estimates of the prevalence of lipodystrophy syndrome and constituent symptoms and to identify correlates of prevalent symptomology. METHODS: Participants in a province-wide HIV/AIDS treatment programme reported morphological and metabolic abnormalities. Probable lipodystrophy was defined as self-report of at least one morphological abnormality or both high cholesterol and triglyceride levels. Explanatory variables investigated included: age; sex; ethnicity; transmission risk group; CD4 cell count; plasma viral load; AIDS diagnosis; duration of infection; alternative therapy use; past, current and duration of use of antiretroviral therapy (ART) by class and specific drug; total duration of ART; and current adherence. Stepwise logistic regression identified possible determinates of lipodystrophy. RESULTS: Of 1035 participants, 50% appeared to have probable lipodystrophy, with 36% reporting peripheral wasting, 33% abdominal weight gain, 6% buffalo hump, and 10 and 12% increased triglyceride or cholesterol levels, respectively. In multivariate analysis, lipodystrophy was associated with older age (per year) (AOR 1.03; 95% CI 1.01, 1.04), the use of ingested alternative therapies (AOR 1.46; 95% CI 1.06, 2.01), having ever used protease inhibitors (PI) (AOR 2.63; 95% CI 1.89, 3.66), and duration of stavudine treatment (per year) (AOR 1.35; 95% CI 1.15, 1.58). In analysis limited to participants exposed to PI, after similar adjustment, the duration of lamivudine rather than stavudine treatment was associated with lipodystrophy (AOR 1.32; 95% CI 1.13, 1.53). CONCLUSION: Increased risk of abnormalities is associated with the use of PI, and the duration of stavudine and lamivudine treatment after adjustment for personal characteristics, clinical disease stage, duration of infection and detailed treatment history. PMID- 11216933 TI - Tolerance of efavirenz in children. AB - OBJECTIVE: To extend the limited knowledge of efavirenz tolerance in children. METHOD: An observational study of 33 children given efavirenz combined with various others agents and followed in a single institution. RESULTS: Fifteen (42%) of the children presented at least one clinically discernable side effect, cutaneous (n = 5), nervous system (n = 10), or both (n = 2). Intolerance led to treatment interruption in seven children but the main symptom was transitory dizziness or other signs similar to those observed in adults. CONCLUSION: Early, often transient nervous system side effects require careful preparation with the child and his family to avoid premature and inadequate withdrawal from treatment. PMID- 11216934 TI - An evaluation of a thicker versus a standard condom with gay men. AB - OBJECTIVES: Although thicker (stronger) condoms are advocated in western Europe for anal intercourse between men, empirical evidence supporting their greater efficacy is lacking. The present study aimed to determine whether a thicker condom is less likely to fail (break or slip off) than a standard (regular thickness) condom, and to establish factors associated with condom failure among gay men. DESIGN: A total of 283 homosexual couples participated in a double blind, randomized, controlled trial of a standard and a thicker condom. METHODS: Each couple was allocated nine of either condom type. Data were collected on user characteristics, and a questionnaire completed immediately after the use of each condom. The thicker and the standard condoms were used by 142 and 141 couples, respectively. RESULTS: No significant differences were found between the two condom types with respect to either clinical or non-clinical definitions of failure (breakage and slippage). With instances of inappropriate use removed, failure rates for the standard and the thicker condom were low at 2.5 and 2.3%, respectively. User characteristics associated with breakage were lower educational achievement, lack of confidence in condom use, and a history of condom breakage. Behaviours associated with breakage were unrolling the condom before fitting to the penis, longer penis length, absence of additional lubricant, the use of inappropriate lubricant, and longer duration of intercourse. CONCLUSION: Breakage and slippage rates were low for both condom types. There is no evidence from the present investigation to support the use of stronger (thicker) condoms over standard strength condoms among gay men. The appropriate use of additional lubricant should be encouraged. PMID- 11216935 TI - Cytomegalovirus seroconversion as a cofactor for progression to AIDS. AB - OBJECTIVE: To study the impact of cytomegalovirus (CMV) seroconversion on HIV-1 disease progression. DESIGN: Follow-up of CMV-seronegative subjects enrolled in the French SEROCO/HEMOCO cohorts of HIV-infected subjects. METHODS: A total of 290 subjects were CMV-seronegative at enrolment in the cohort. Serological testing for CMV infection was done at enrolment and then every 6 months in CMV seronegative subjects. The person-years method was used to calculate the incidence of CMV seroconversion. After adjustment for age, the CD4+ cell count at enrolment and the HIV exposure group in a Cox model, we studied CMV seroconversion as a time-dependent variable in progression to a CD4+ cell count below 200 x 10(6) cells/l and to clinical AIDS. RESULTS: Overall, 61 CMV seroconversions were observed. The overall incidence rate was 4.4 per 100 person years [95% confidence interval (CI), 3.3-5.5]. The risk of progression to a CD4+ cell count below 200 x 10(6) cells/l was not increased in CMV seroconverters. However, the risk of progression to AIDS was increased two-fold in CMV seroconverters compared with subjects who remained CMV-seronegative [relative risk (RR) = 2.09; 95% CI, 1.16-3.74; P = 0.01]. CONCLUSION: This analysis of 61 CMV seroconversions, the largest study in the literature, confirms the impact of recent CMV infection on progression to AIDS. PMID- 11216937 TI - Latex condoms, human behavior, and public health. PMID- 11216936 TI - Using phylogenetic analysis to trace HIV-1 migration among western European injecting drug users seroconverting from 1984 to 1997. AB - OBJECTIVE: To reconstruct the epidemiological relationships of the HIV epidemics among injecting drug users (IDU) in western Europe. METHODS: HIV env V3 sequences of and epidemiological data were obtained from 145 IDU who seroconverted in three sequential periods: 1984-1988, 1989-1992 and 1993-1997. The sequences were phylogenetically analysed and examined for signature patterns characteristic of northern European IDU, including the conserved GGC codon in the V3 loop. RESULTS: Subpopulations of genetically related HIV strains were observed in Italy, France, Scotland and Spain, in contrast to the Netherlands, Austria and Switzerland. This difference between the two groups of countries suggests that the HIV epidemics amongst IDU in the latter group was caused by multiple virus introductions. In Edinburgh and the surrounding area, most IDU were infected with the same GGC strain over the 12-year study period. The epidemic among IDU in north-western Europe started with GGC viruses, whereas in south-western Europe non-GGC viruses predominated. This geographical separation has faded during the course of the epidemic, most likely because of virus exchange among IDU populations. PMID- 11216938 TI - The HIV-associated lipodystrophy syndrome: research, results, yet more questions. PMID- 11216939 TI - Treatment interruption after one year of triple nucleoside analogue therapy for primary HIV infection. PMID- 11216940 TI - Need for increased dose of warfarin in HIV patients taking nevirapine. PMID- 11216941 TI - Equivalent osteopenia in HIV-infected individuals studied before and during the era of highly active antiretroviral therapy. PMID- 11216943 TI - Incidence of clinical lipodystrophy in HIV-infected patients treated during primary infection. PMID- 11216942 TI - Long-term remission of an AIDS-related primary effusion lymphoma with antiviral therapy. PMID- 11216944 TI - Compartmentalization of HIV-1 according to antiretroviral therapy: viral loads are correlated in blood and semen but poorly in blood and saliva. PMID- 11216945 TI - The role of social marketing in sexually transmitted diseases/HIV protection in 4600 sexual contacts in urban Zimbabwe. PMID- 11216946 TI - Severe anaphylactic shock after rechallenge with abacavir without preceding hypersensitivity. PMID- 11216947 TI - Are 'buffalo hump' syndrome, Madelung's disease and multiple symmetrical lipomatosis variants of the same dysmetabolism? PMID- 11216948 TI - Liver transplantation for an HIV-positive patient in the era of highly active antiretroviral therapy. PMID- 11216949 TI - Epidemiology and natural history of atrial fibrillation: clinical implications. AB - With a substantial impact on morbidity and mortality, the growing "epidemic" of atrial fibrillation (AF) intersects with a number of conditions, including aging, thromboembolism, hemorrhage, hypertension and left ventricular dysfunction. Currently, the epidemiology and natural history of AF govern all aspects of its clinical management. The ongoing global investigative efforts toward understanding AF are also driven by epidemiologic findings. New developments, by affecting the natural history of the disease, could eventually alter the nature of decision making in patients with AF. The crucial issue of rate versus rhythm control awaits completion of the AF Follow-up Investigation of Rhythm Management trial. The processes of electrical and structural remodeling that perpetuate AF appear to be reversible. In the era of functional genomics, the molecular basis of this ubiquitous arrhythmia is in the process of being defined. Unraveling the molecular genetics of AF might provide new insights into the structural and electrical phenotypes resulting from genetic mutations and, as such, new approaches to treatment of this arrhythmia at the ion channel and cellular levels. Thus, current adverse trends are superimposed on a background of a rapidly developing knowledge base and potentially exciting new therapeutic options. Consequently, an understanding of the epidemiology and natural history of AF is crucial to the future allocation of resources and the utilization of an expanding range of therapies aimed at reducing the impact of this disease on a changing patient population. PMID- 11216950 TI - Utility of B-type natriuretic peptide in the diagnosis of congestive heart failure in an urgent-care setting. AB - OBJECTIVES: The goal of this study was to evaluate the utility of a rapid "bedside" technique for measurement of B-type natriuretic peptide (BNP) in the diagnosis of congestive heart failure (CHF) in an urgent-care setting. BACKGROUND: B-type natriuretic peptide is a protein secreted from the cardiac ventricles in response to pressure overload. One potential application of measurements of BNP in blood is distinguishing dyspnea due to CHF from other causes. METHODS: B-type natriuretic peptide concentrations were measured in a convenience sample of 250 predominantly male (94%) patients presenting to urgent care and emergency departments of an academic Veteran's Affairs hospital with dyspnea. Results were withheld from clinicians. Two cardiologists retrospectively reviewed clinical data (blinded to BNP measurements) and reached a consensus opinion on the cause of the patient's symptoms. This gold standard was used to evaluate the diagnostic performance of the BNP test. RESULTS: The mean BNP concentration in the blood of patients with CHF (n = 97) was higher than it was in patients without (1,076 +/- 138 pg/ml vs. 38 +/- 4 pg/ml, p < 0.001). At a blood concentration of 80 pg/ml, BNP was an accurate predictor of the presence of CHF (95%); measurements less than this had a high negative predictive value (98%). The overall C-statistic was 0.97. In multivariate analysis, BNP measurements added significant, independent explanatory power to other clinical variables in models predicting which patients had CHF. The availability of BNP measurements could have potentially corrected 29 of the 30 diagnoses missed by urgent-care physicians. CONCLUSIONS: B-type natriuretic peptide blood concentration measurement appears to be a sensitive and specific test to diagnose CHF in urgent-care settings. PMID- 11216951 TI - A rapid bedside test for B-type peptide predicts treatment outcomes in patients admitted for decompensated heart failure: a pilot study. AB - OBJECTIVES: The goal of this study was to determine if B-type natriuretic peptide (BNP) levels predict outcomes of patients admitted with decompensated heart failure. BACKGROUND: Treatment of decompensated congestive heart failure (CHF) has often been based on titration of drugs to relieve patient's symptoms, a case that could be made for attempting to also treat neurohormonal abnormalities. Because BNP reflects both elevated left ventricular pressure as well as neurohormonal modulation, we hypothesized that BNP might be useful in assessing outcomes in patients admitted with decompensated CHF. METHODS: We followed 72 patients admitted with decompensated New York Heart Association class III to IV CHF, measuring daily BNP levels. We then determined the association between initial BNP measurement and the predischarge or premoribund BNP measurement and subsequent adverse outcomes (death and 30-day readmission). RESULTS: Of the 72 patients admitted with decompensated CHF, 22 end points occurred (death: n = 13, readmission: n = 9). In these patients, BNP levels increased during hospitalization (mean increase, 233 pg/ml, p < 0.001). In patients without end points, BNP decreased (mean decrease 215 pg/ml). Univariate analysis revealed that the last measured BNP was strongly associated with the combined end point. In patients surviving hospitalization, BNP discharge concentrations were strong predictors of subsequent readmission (area under the receiver operator curve of 0.73). CONCLUSIONS: In patients admitted with decompensated CHF, changes in BNP levels during treatment are strong predictors for mortality and early readmission. The results suggest that BNP levels might be used successfully to guide treatment of patients admitted for decompensated CHF. PMID- 11216952 TI - Endothelial dysfunction in patients with chronic heart failure: systemic effects of lower-limb exercise training. AB - OBJECTIVES: We sought to analyze the systemic effects of lower-limb exercise training (ET) on radial artery endothelial function in patients with chronic heart failure (CHF). BACKGROUND: Local ET has the potential to improve local endothelial dysfunction in patients with CHF. However, it remains unclear whether the systemic effects can be achieved by local ET. METHODS: Twenty-two male patients with CHF were prospectively randomized to either ET on a bicycle ergometer (ET group, n = 11; left ventricular ejection fraction [LVEF] 26 +/- 3%) or an inactive control group (group C, n = 11; LVEF 24 +/- 2%). At the beginning of the study and after four weeks, endothelium-dependent and -independent vasodilation of the radial artery was determined by intra-arterial infusion of acetylcholine (ACh-7.5, 15 and 30 microg/min) and nitroglycerin (0.2 mg/min). The mean internal diameter (ID) of the radial artery was assessed using a high resolution ultrasound system (NIUS-02, Asulab Research Laboratories, Neuchatel, Switzerland) with a 10-MHz probe. RESULTS: After four weeks of ET, patients showed a significant increase in the baseline-corrected mean ID in response to ACh (30 microg/min), from 33 +/- 10 to 127 +/- 25 microm (p < 0.001 vs. control group at four weeks). In the control group, the response to ACh (30 microg/min) remained unchanged. Endothelium-independent vasodilation was similar in both groups at the beginning of the study and at four weeks. In the training group, increases in agonist-mediated, endothelium-dependent vasodilation correlated to changes in functional work capacity (r = 0.63, p < 0.05). CONCLUSIONS: In patients with stable CHF, bicycle ergometer ET leads to a correction of endothelial dysfunction of the upper extremity, indicating a systemic effect of local ET on endothelial function. PMID- 11216953 TI - Modulation of alveolar-capillary sodium handling as a mechanism of protection of gas transfer by enalapril, and not by losartan, in chronic heart failure. AB - OBJECTIVES: We sought to compare the protective efficacy of enalapril and losartan on lung diffusion in chronic heart failure (CHF). BACKGROUND: In CHF, hydrostatic overload causes disruption of the alveolar-capillary membrane and depression of carbon monoxide diffusion (DCO); enalapril improves DCO through mechanisms still undefined; and saline infusion in the pulmonary circulation worsens DCO, putatively because of an upregulated sodium transport to the alveolar interstitium. We investigated whether enalapril modulates sodium handling and whether losartan shares the same properties. METHODS: In 29 patients with CHF, DCO, its membrane diffusion subcomponent (DM) and right atrial and pulmonary wedge pressures were monitored during saline infusion, in the control condition, during enalapril therapy (20 mg/day) for two weeks and after crossover to losartan (50 mg/day) for two weeks (first 20 patients), or after the combination of enalapril with aspirin (325 mg/day) for one week (last 9 patients). RESULTS: Saline, 150 ml, lowered DCO (-7.9%; p < 0.01) and DM (-9.9%; p < 0.01) without hydrostatic variations. Responses to 750 ml of saline were qualitatively similar. After treatment with enalapril, baseline DCO (p < 0.01) and DM (p < 0.01) were augmented; after sodium loading, the percent reductions of DCO (p < 0.01) and DM (p < 0.01) were comparable to those before it, resulting in higher absolute values. This suggests that the greater the gas conductance improvement with enalapril, the lower the impedance with saline. Losartan was ineffective on gas transfer at rest and under salt challenge. Aspirin counteracted the benefits of enalapril. CONCLUSIONS: In CHF, enalapril protects lung diffusion, possibly through a prostaglandin-mediated modulation of sodium overfiltration to the alveolar interstitium; losartan does not share this ability. PMID- 11216954 TI - Dilated cardiomyopathy in dialysis patients--beneficial effects of carvedilol: a double-blind, placebo-controlled trial. AB - OBJECTIVES: The aim of this study was to investigate in dialysis patients with symptomatic heart failure New York Heart Association (NYHA) functional class II or III whether the addition of carvedilol to conventional therapy is associated with beneficial effects on cardiac architecture, function and clinical status. BACKGROUND: Congestive heart failure (CHF) in chronic hemodialyzed patients, particularly when associated with dilated cardiomyopathy, represents an ominous complication and is an independent risk factor for cardiac mortality. METHODS: We enrolled 114 dialysis patients with dilated cardiomyopathy. All patients were treated with carvedilol for 12 months in a double-blind, placebo-controlled, randomized trial. The patients underwent M-mode and two-dimensional echocardiography at baseline, 1, 6 and 12 months after the randomization. Each patient's clinical status was assessed using an NYHA functional classification that was determined after 6 and 12 months of treatment. RESULTS: Carvedilol treatment improved left ventricular (LV) function. In the active-treatment group, the increase in LV ejection fraction (from 26.3% to 34.8%, p < 0.05 vs. basal and placebo group) and the reduction of both LV end-diastolic volume (from 100 ml/m2 to 94 ml/m2, p < 0.05 vs. basal and placebo group) and end-systolic volume (from 74 ml/m2 to 62 ml/m2, p < 0.05 vs. basal and placebo group) reached statistical significance after six months of therapy, compared with baseline and corresponding placebo values, and they remained constant at one year of treatment (p < 0.05 vs. basal and placebo group). The clinical status of patients, assessed by NYHA functional classification, improved during the treatment period. Moreover, at the end of the trial, there were no patients in NYHA functional class IV in the carvedilol group, compared with 5.9% of the patients in the placebo arm. CONCLUSIONS: One year of therapy with carvedilol in dialysis patients with CHF and dilated cardiomyopathy reduces LV volumes and improves LV function and clinical status. PMID- 11216955 TI - Effect of beta-blockers on circulating levels of inflammatory and anti inflammatory cytokines in patients with dilated cardiomyopathy. AB - OBJECTIVES: This study was designed to evaluate the beneficial effect of beta blockers on circulating cytokine levels in patients with dilated cardiomyopathy (DCM). BACKGROUND: Elevated circulating levels of inflammatory cytokines have been reported in patients with DCM. However, alterations of the levels of inflammatory and anti-inflammatory cytokines in association with beta-blocker therapy are unknown. METHODS: We studied 32 patients with idiopathic DCM who had been treated with digitalis, diuretics and angiotensin-converting enzyme inhibitors. In addition to this combination therapy, beta-blockers were started in all patients. Serum levels of interleukin (IL)-10, tumor necrosis factor-alpha (TNF-alpha) and soluble TNF receptors (sTNF-R1 and R2) were measured at baseline and 12 weeks after the initiation of beta-blocker therapy. We also measured plasma levels of neurohumoral factors, as well as left ventricular (LV) size and function. Ten age-matched subjects with no cardiac disease served as the control group. RESULTS: Baseline levels of IL-10, TNF-alpha and sTNF-R2 were significantly higher in patients with DCM than in control subjects (p < 0.05). There was a significant positive correlation between IL-10 and TNF-alpha levels (r = 0.545, p = 0.029). The TNF-alpha/IL-10 ratio correlated well with plasma epinephrine levels (r = 0.677, p = 0.025), and the level of sTNF-R2 was closely related to LV size. Serum levels of IL-10, TNF-alpha and sTNF-R2 were significantly decreased during beta-blocker therapy (p < 0.005). CONCLUSIONS: Our findings indicate that beta-blockers have an important immunoregulatory role in modifying the dysregulated cytokine network in DCM. This effect of beta-blockers may be partly responsible for the efficacy of therapeutic drugs for heart failure. PMID- 11216956 TI - Autoantibodies against the second extracellular loop of beta1-adrenergic receptors predict ventricular tachycardia and sudden death in patients with idiopathic dilated cardiomyopathy. AB - OBJECTIVES: We sought to define the clinical and long-term prognostic implications of autoantibodies that act against the second extracellular loop of beta1-adrenergic receptors (ARs) in patients with idiopathic dilated cardiomyopathy (IDC). BACKGROUND: Although autoantibodies directed against various domains of beta-ARs are found in patients with IDC, only a subgroup against the second extracellular domain of beta1-ARs exerts intrinsic sympathomimetic-like actions on human beta-ARs. It is suggested that the autoantibodies take part in the pathophysiology of IDC and may affect long-term prognosis of patients with this disorder. METHODS: Sera from 104 patients with IDC were screened for autoantibodies that act against the second extracellular loop of beta1-ARs by enzyme-linked immunosorbent assay, using a synthetic peptide corresponding to the domain. Relations of the autoantibodies to clinical variables and long-term prognosis were assessed by multivariate analysis. RESULTS: Autoantibodies were detected in 40 patients (38%). Multifocal ventricular premature contractions (p < 0.01) and ventricular tachycardia (VT; p < 0.01) were more common in autoantibody-positive than in autoantibody-negative patients, although no differences in cardiac function or neurohormonal levels were demonstrated. The presence of autoantibodies (p = 0.001) and a low left ventricular ejection fraction (LVEF <30%; p = 0.02) were independent predictors of VT. Sudden death was independently predicted by the presence of autoantibodies (p = 0.03), as well as by LVEF <30% (p = 0.01), whereas total mortality was predicted only by LVEF <30% (p = 0.001). CONCLUSIONS: Autoantibodies directed against the second extracellular loop of beta1-ARs were closely related to serious ventricular arrhythmias in patients with IDC, and the presence of autoantibodies independently predicted sudden death. These autoantibodies may contribute to electrical instability in patients with IDC. PMID- 11216957 TI - Estrogen-induced small low density lipoprotein particles may be atherogenic in postmenopausal women. AB - OBJECTIVES: The purpose of this study was to investigate the susceptibility of estrogen-induced small low density lipoprotein (LDL) particles to oxidation. BACKGROUND: Estrogen replacement therapy in postmenopausal women has an antioxidant effect that opposes oxidation of LDL particles. Estrogen-induced increases in plasma triglyceride concentrations, however, decrease LDL particle size, which may act counter to this antioxdant effect. It has not been evaluated whether estrogen-induced small LDL particles are atherogenic. METHODS: In 24 lean and healthy postmenopausal women treated with conjugated equine estrogen (0.625 mg daily) for three months, plasma lipid concentrations and diameter of LDL particles were measured before and after therapy. Susceptibility of LDL to oxidation was determined by measuring the concentration of thiobarbituric acid reactive substances (TBARS) after incubation with CuSO4. RESULTS: Estrogen significantly decreased plasma concentrations of total cholesterol, LDL cholesterol and apolipoprotein B, while increasing concentrations of triglyceride, high-density lipoprotein cholesterol and apolipoprotein A-I. Estrogen-induced changes in LDL particle diameter correlated negatively with changes in plasma triglyceride concentrations (r = -0.55, p < 0.005) and with changes in concentrations of LDL-derived TBARS (r = -0.49, p < 0.005). In subjects with substantial estrogen-induced plasma triglyceride increases, estrogen significantly reduced the diameter of LDL particles (p < 0.05) and significantly increased the concentration of LDL-derived TBARS (p < 0.05). In contrast, estrogen significantly reduced the concentration of LDL-derived TBARS (p < 0.05) and caused no significant change in LDL particle diameter in subjects whose plasma triglyceride concentration was unchanged with estrogen therapy. CONCLUSIONS: Because estrogen-induced plasma triglyceride increases may produce small LDL particles that are more susceptible to oxidation, antioxidant effects of estrogen might be offset in patients showing such a triglyceride increase. PMID- 11216958 TI - Estrogens, lipids and cardiovascular disease: no easy answers. PMID- 11216959 TI - Lipoprotein(a) further increases the risk of coronary events in men with high global cardiovascular risk. AB - OBJECTIVES: This prospective population study was conducted to assess the role of elevated lipoprotein(a) [Lp(a)] as a coronary risk factor. BACKGROUND: The role of elevated Lp(a) as a risk factor for coronary heart disease is controversial. In addition, little attention has been paid to the interaction of Lp(a) with other risk factors. METHODS: A total of 788 male participants of the Prospective Cardiovascular Munster (PROCAM) study aged 35 to 65 years were followed for 10 years. Both Lp(a) and traditional cardiovascular risk factors (e.g., age, low density lipoprotein [LDL] cholesterol, high density lipoprotein [HDL] cholesterol, triglycerides, systolic blood pressure, cigarette smoking, diabetes mellitus, angina pectoris, and family history of myocardial infarction) were evaluated in 44 men who suffered from myocardial infarction, and in 744 men who survived without major coronary events or stroke. A multiple logistic function algorithm was used to estimate global cardiovascular risk by the combined effects of traditional risk factors. RESULTS: Overall, the risk of a coronary event in men with an Lp(a) > or =0.2 g/liter was 2.7 times that of men with lower levels (95% confidence interval [CI]: 1.4 to 5.2). This increase in risk was most prominent in men with LDL cholesterol level > or =4.1 mmol/liter (relative risk [RR]: 2.6; 95% CI: 1.2 to 5.7), with HDL cholesterol < or =0.9 mmol/liter (RR 8.3; 95% CI: 2.0 to 35.5), with hypertension (RR 3.2; 95% CI: 1.4 to 7.2), or within the two highest global risk quintiles (relative risk: 2.7; 95% CI: 1.3 to 5.7). CONCLUSIONS: Lp(a) increases the coronary risk, especially in men with high LDL cholesterol, low HDL cholesterol, hypertension and/or high global cardiovascular risk. PMID- 11216960 TI - Irbesartan, an angiotensin type 1 receptor inhibitor, regulates markers of inflammation in patients with premature atherosclerosis. AB - OBJECTIVES: This study assessed the role of angiotensin II type 1 (AT1) receptor antagonists on inflammatory mechanisms involved in atherogenesis. Specific inflammatory markers included solubilized tumor necrosis factor-alpha receptor II (sTNF-alphaRII), vascular cell adhesion molecule-1 (VCAM-1) and superoxide. In addition, the AT1 receptor blocker irbesartan was evaluated for its ability to suppress these markers in individuals with atherosclerosis. BACKGROUND: Mechanisms involved in the complex process of atherogenesis include alterations in the inflammatory responses. The use of compounds that suppress these responses may reduce the degree of damage seen in atherosclerosis. METHODS: With a cross sectional study design, 33 normotensive patients with stable coronary artery disease (CAD) were treated with irbesartan for a 24-week period. These patients were compared against a control population with no known coronary atherosclerosis. Marker levels were measured by enzyme-linked immunosorbent assay technique and lucigenin chemiluminescence assay and statistically evaluated by two-way repeated measures analysis of variance. RESULTS: All patients with coronary artery disease had increased levels of inflammatory molecules over those of control patients. Treatment with irbesartan in these patients significantly reduced levels of inflammatory molecules measured. Soluble VCAM-1 levels were reduced by 36%; soluble TNF-alpha levels were reduced by 54% and superoxide level decreased by 52%. Maximal suppression of inflammatory markers by irbesartan therapy in patients with CAD was seen at 12 weeks. CONCLUSIONS: The effect of irbesartan on each inflammatory marker is significant. Our results show that use of irbesartan may retard the inflammatory process seen in premature forms of atherosclerosis. PMID- 11216961 TI - Periodontal disease and risk of subsequent cardiovascular disease in U.S. male physicians. AB - OBJECTIVES: We sought to prospectively assess whether self-reported periodontal disease is associated with subsequent risk of cardiovascular disease in a large population of male physicians. BACKGROUND: Periodontal disease, the result of a complex interplay of bacterial infection and chronic inflammation, has been suggested to be a predictor of cardiovascular disease. METHODS: Physicians' Health Study I was a randomized, double-blind, placebo-controlled trial of aspirin and beta-carotene in 22,071 U.S. male physicians. A total of 22,037 physicians provided self-reports of presence or absence of periodontal disease at study entry and were included in this analysis. RESULTS: A total of 2,653 physicians reported a personal history of periodontal disease at baseline. During an average of 12.3 years of follow-up, there were 797 nonfatal myocardial infarctions, 631 nonfatal strokes and 614 cardiovascular deaths. Thus, for each end point, the study had >90% power to detect a clinically important increased risk of 50%. In Cox proportional hazards regression analysis adjusted for age and treatment assignment, physicians who reported periodontal disease at baseline had slightly elevated, but statistically nonsignificant, relative risks (RR) of nonfatal myocardial infarction, (RR, 1.12; 95% confidence interval [CI], 0.92 to 1.36), nonfatal stroke (RR, 1.10; CI, 0.88 to 1.37) and cardiovascular death (RR, 1.20; CI, 0.97 to 1.49). Relative risk for a combined end point of all important cardiovascular events (first occurrence of nonfatal myocardial infarction, nonfatal stroke or cardiovascular death) was 1.13 (CI, 0.99 to 1.28). After adjustment for other cardiovascular risk factors, RRs were all attenuated and nonsignificant. CONCLUSIONS: These prospective data suggest that self-reported periodontal disease is not an independent predictor of subsequent cardiovascular disease in middle-aged to elderly men. PMID- 11216962 TI - Correlation of coronary calcification and angiographically documented stenoses in patients with suspected coronary artery disease: results of 1,764 patients. AB - OBJECTIVES: This study correlated the electron beam computed tomographic (EBCT) calcium scores with the results of coronary angiography in symptomatic patients in order to assess its value to predict or exclude significant coronary artery disease (CAD). BACKGROUND: Electron beam computed tomography is a sensitive method to detect coronary calcium. However, it is unclear whether it may play a role as a filter before invasive procedures in symptomatic patients. METHODS: A total of 1,764 patients (1,225 men and 539 women) with suspected CAD from a single center were included in our study. All patients underwent calcium screening with EBCT (C150XP Imatron) and conventional coronary angiography. RESULTS: Fifty-six percent of men and 47% of women revealed significant coronary stenoses (> or =50%). Total exclusion of coronary calcium (14% of the study group) was associated with an extremely low probability of stenosis (<1%). With calcium scores > or =20th, > or =100th or > or =75th percentile of age groups, the sensitivity to detect stenoses decreased to 97%, 93% and 81%, respectively, in men and to 98%, 82% and 76%, respectively, in women. At the same time, the specificity increased up to 77% in men and women. There was a significant difference in coronary calcium between men and women in all age groups; however, receiver-operating characteristic curves indicated that the test can be performed with equal accuracy in all of these subgroups. CONCLUSIONS: Calcium screening with EBCT is a highly sensitive and moderately specific test to predict stenotic disease. Exclusion of coronary calcium defines a substantial subgroup of patients, albeit symptomatic, with a very low probability of significant stenoses. PMID- 11216963 TI - Enhanced detection of reversible perfusion defects by Tc-99m sestamibi compared to Tc-99m tetrofosmin during vasodilator stress SPECT imaging in mild-to-moderate coronary artery disease. AB - OBJECTIVES: We prospectively compared dipyridamole single-photon emission computed tomography (SPECT) imaging with Tc-99m sestamibi and Tc-99m tetrofosmin for the detection of reversible perfusion defects in patients with mild-to moderate coronary artery disease. BACKGROUND: Tc-99m tetrofosmin has a lower first-pass myocardial extraction fraction compared to Tc-99m sestamibi and thus could underestimate mild perfusion defects. METHODS: Eighty-one patients with 50% to 90% stenosis in one or two major epicardial vessels without previous myocardial infarction, and seven with <5% probability of coronary artery disease underwent dipyridamole SPECT imaging with both agents. The SPECT data were analyzed quantitatively. RESULTS: Tc-99m sestamibi detected reversible perfusion defects in a greater number of segments (total 363 and 285, p < 0.001, and mean +/- SD, 2.2 +/- 3.0 and 1.8 +/- 2.5 per patient, p = 0.008, for Tc-99m sestamibi and Tc-99m tetrofosmin, respectively), demonstrated a larger extent of perfusion defect (mean +/- SD, 15.8% +/- 12.3% and 12.0% +/- 11.4%, p < 0.03, for Tc-99m sestamibi and Tc-99m tetrofosmin, respectively) and more often correctly identified patients with disease in more than one coronary artery (p = 0.02). There was better defect contrast with Tc-99m sestamibi (defect/normal wall count ratios were 0.60 +/- 0.15 vs. 0.73 +/- 0.14 for Tc-99m sestamibi and Tc99m tetrofosmin, respectively, p = 0.01, for reversible defects seen in identical segments with both agents; and 0.73 +/- 0.16 vs 0.79 +/- 0.17, respectively, p <0.01, for reversible defects detected with either agent alone). There was no significant difference in diagnostic sensitivity or image quality. CONCLUSIONS: These differences between two commonly used tracers may have significant diagnostic and prognostic implications. PMID- 11216964 TI - Myocardial perfusion imaging findings and the role of adenosine in the warm-up angina phenomenon. AB - OBJECTIVES: This study examined the roles of myocardial perfusion and adenosine in warm-up angina. BACKGROUND: In warm-up angina, neither the role of an adenosine-mediated mechanism, as is found in experimental ischemic preconditioning, nor of increased myocardial perfusion is well defined. METHODS: In substudy A, a single-photon emission computed tomography (SPECT)-thallium-201 exercise test was performed by 12 subjects with ischemic heart disease on three occasions one week apart. The third test was preceded by a warm-up test. The extent of the thallium deficit and its intensity on the third test were compared with the baseline tests controlling for the heart rate-systolic blood pressure product (RPP) at thallium injection. In substudy B, 12 similar subjects did two successive exercise tests at two separate sessions and received the adenosine antagonist, aminophylline (intravenous 5 mg/kg bolus and 0.9 mg/kg/h infusion) at one session, and equivalent saline at the other session. Change in ischemic threshold (RPP at 1 mm ST segment depression) and in maximum ST depression adjusted for RPP were analyzed. RESULTS: In substudy A, despite a significant attenuation of electrocardiogram indexes of myocardial ischemia between the baseline and third (warmed-up) tests, the thallium extent deficits (20.8 +/- 15.1% and 16.8 +/- 12.4%) and intensity deficits (41.2 +/- 12.6% and 39.3 +/- 12.6%) did not differ significantly. In substudy B, the increase in ischemic threshold on re-exercise was unaffected by aminophylline. Adjusted maximum ST depression even decreased to a greater extent on re-exercise with aminophylline (by 51 +/- 21%) than with saline (by 32 +/- 19%) (p = 0.012). CONCLUSIONS: While warm-up angina is associated with a significant attenuation of exercise electrocardiogram indexes of ischemia, it is unaccompanied by significant changes in SPECT perfusion and does not appear to be mediated by an adenosine-dependent mechanism since it is not blocked by aminophylline. Thus, its mechanism, which appears distinct from experimental ischemic preconditioning, remains unidentified. PMID- 11216965 TI - Reduction of exercise-induced myocardial ischemia during add-on treatment with the angiotensin-converting enzyme inhibitor enalapril in patients with normal left ventricular function and optimal beta blockade. AB - OBJECTIVES: We sought to study the effect of angiotensin-converting enzyme inhibition on exercise-induced myocardial ischemia. BACKGROUND: Although angiotensin-converting enzyme inhibitors have been shown to reduce ischemic events after myocardial infarction, few data are available regarding their direct anti-ischemic effects in patients with coronary artery disease. METHODS: We studied 43 patients (average age 63 +/- 8 years) with exercise-induced myocardial ischemia (> or =0.1 mV ST depression, despite optimal beta blockade) and normal left ventricular function (ejection fraction >0.50). In a double-blind, placebo controlled parallel design, patients were treated with angiotensin-converting enzyme inhibitor (enalapril 10 mg twice daily) or placebo. Assessments were made after three weeks (short-term) and 12 weeks (long-term). RESULTS: At baseline, the groups were well matched for all clinical characteristics. After three weeks, there was a slight but not significant increase in time to 0.1 mV ST depression in both groups (p = NS); rate pressure product (RPP = heart rate x systolic blood pressure) was also unaffected. After 12 weeks, however, time to 0.1 mV ST depression further increased in the enalapril group (5.6 +/- 1.9 min) but was unchanged in the placebo group (4.4 +/- 1.3 min; p < 0.05 between groups). In contrast, RPP was not affected. Concentrations of both atrial and brain natriuretic peptides at peak exercise tended to be lower by enalapril, if compared to placebo (p = NS). CONCLUSIONS: Angiotensin-converting enzyme inhibition may reduce exercise-induced myocardial ischemia in patients with normal left ventricular function. Further studies are needed to elucidate the mechanisms involved. PMID- 11216966 TI - Effects of long-term, moderate-intensity oral anticoagulation in addition to aspirin in unstable angina. The Organization to Assess Strategies for Ischemic Syndromes (OASIS) Investigators. AB - OBJECTIVES: We sought to evaluate whether oral anticoagulant (AC) therapy given for five months was superior to standard (control) therapy in patients with unstable angina receiving aspirin. BACKGROUND: The long-term risk of myocardial infarction (MI) or death remains high in patients with unstable angina, despite the use of aspirin. Therefore, additional treatments are necessary. METHODS: Of the 10,141 patients entering the main trial, 3,712 were randomized 12 to 48 h later to receive oral AC therapy (n = 1,848) or standard therapy (n = 1,864). RESULTS: One-hundred forty patients (7.6%) suffered from cardiovascular death, MI or stroke while receiving oral AC, compared with 155 patients (8.3%) on standard therapy (relative risk [RR] 0.90, 95% confidence interval [CI] 0.72 to 1.14; p = 0.40). The rates of the primary outcomes plus refractory angina were 16.7% (n = 308) versus 17.5% (n = 327) (RR 0.95, 95% CI 0.81 to 1.11; p = 0.53). Countries were divided into good or poor compliers (based on the use of oral AC above or below 70% at 35 days), without knowledge of results by country. In good-complier countries, oral AC was discontinued in only 10.4% of patients at seven days and in 23.6% by five months, compared with 27.6% and 44.9%, respectively, in poor complier countries. There were significant reductions in the risks of both the primary (6.1% vs. 8.9%; RR 0.68, 95% CI 0.48 to 0.95; p = 0.02) and secondary outcomes (11.9% vs. 16.5%; RR 0.70, 95% CI 0.55 to 0.90; p = 0.005) with oral AC in the good-complier countries. There was little difference in the poor-complier countries (9.0% vs. 7.8% for the primary and 21.3% vs. 18.5% for the secondary outcomes, tests for interactions comparing the RRs for the primary and secondary outcomes were p < 0.02 and p = 0.002, respectively, between the two sets of countries). In the overall study, there was an excess of major bleeding (2.7% vs. 1.3%; p = 0.004), which was larger in the good-complier countries (RR 2.71) compared with the poor-complier countries (RR 1.58). There were also reductions in cardiac catheterization (RR 0.80; p = 0.004) and coronary revascularization procedures (RR 0.82; p = 0.06) in the good-complier countries, but not in the poor-complier countries (RR 0.98 and 1.06, respectively, p for interaction of 0.06 and 0.04, respectively). CONCLUSIONS: Overall, oral AC led to a small, nonsignificant reduction in the risk of the primary and secondary outcomes. Stratifying the countries or centers by their rates of compliance to oral AC suggested that good compliance to oral AC could potentially lead to clinically important reductions in major ischemic cardiovascular events. PMID- 11216967 TI - Interaction between chemokines and oxidative stress: possible pathogenic role in acute coronary syndromes. AB - OBJECTIVES: We sought to study the relationships between chemokines and oxidative stress in acute coronary syndrome. BACKGROUND: In view of existing knowledge on the participation of leukocytes and oxidative stress in the pathogenesis of acute coronary syndrome, we hypothesized that chemokines may play a role in recruiting and activating leukocytes in this disorder. METHODS: The levels of chemokines and oxidative stress were studied in 38 patients with stable and 38 with unstable angina and in 20 controls. In separate in vitro experiments the effect of chemokines on reactive oxygen species in monocytes and the effect of antioxidants on chemokine levels in these cells were also studied. RESULTS: 1) Angina patients had raised serum levels of chemokines in both cross-sectional and longitudinal testing, with particularly high levels of interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory peptide (MIP)-1-alpha in unstable disease. 2) T cells, and particularly monocytes, seem to contribute to the raised IL-8, MCP-1 and MIP-1-alpha levels in unstable angina. 3) Concomitantly, and significantly correlated with MCP-1 and IL-8 levels, stable and particularly unstable angina patients had decreased plasma levels of antioxidants and increased lipid peroxidation, suggesting enhanced oxidative stress. 4) Monocyte chemoattractant protein-1 enhanced the generation of O2- in monocytes from unstable angina patients, and the antioxidant glutathione monoethyl ester suppressed the production of IL-8 and MCP-1 in these cells. CONCLUSIONS: Our findings suggest an interaction between chemokines and oxidative stress in unstable angina. This interaction may represent a vicious circle involved in the pathogenesis of acute coronary syndromes. PMID- 11216968 TI - Therapeutic value of eptifibatide at community hospitals transferring patients to tertiary referral centers early after admission for acute coronary syndromes. PURSUIT Investigators. AB - OBJECTIVES: We aimed to evaluate the benefits of the glycoprotein (GP) IIb/IIIa antagonist, eptifibatide, after patients with acute coronary syndromes (ACS) were admitted to hospitals that approach revascularization for ACS through early transfer to tertiary referral centers. BACKGROUND: Across a variety of hospital settings, GP IIb/IIIa inhibition, after patients were admitted to the hospital for non-ST segment elevation ACS, is associated with a reduction in death or myocardial infarction (MI) before and during a percutaneous coronary intervention. METHODS: The outcomes of 429 patients from 153 sites in the Platelet glycoprotein IIb/IIIa in unstable angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, who were transferred during study drug infusion ("transfer patients"), were compared with those of 1,987 patients who either remained in the hospital at those sites or were transferred after study drug termination ("nontransfer patients"). RESULTS: The baseline characteristics of transfer and nontransfer patients were similar. Patients receiving eptifibatide were transferred less frequently than those receiving placebo (16% vs. 20%, p = 0.014). Transfer patients underwent more procedures and experienced a greater 30-day incidence of death or MI, as compared with nontransfer patients (21% vs. 12%, p = 0.001). Eptifibatide was associated with a reduction in death or MI through 30 days, independent of transfer status (2.5% absolute reduction), as well as for those transferred (5.5% absolute reduction). CONCLUSIONS: For patients with ACS admitted to community hospitals, eptifibatide is associated with a reduced need for transfer and improved clinical outcomes. PMID- 11216969 TI - The effects of contemporary use of coronary stents on in-hospital mortality. Registry Committee of the Society for Cardiac Angiography and Interventions. AB - OBJECTIVES: This study was designed to determine the effect of coronary stents on in-hospital mortality. BACKGROUND: Despite extensive use of stents for percutaneous coronary interventions (PCIs), their effect on serious in-hospital events, especially mortality, is not well defined. METHODS: A cohort study was performed using 16,811 consecutive native-vessel PCI procedures performed on patients in the Society for Cardiac Angiography & Interventions Registry from July 1, 1996, through December 31, 1998. Patients undergoing balloon-only angioplasty were compared with those receiving a planned or unplanned stent. Procedures with other devices were excluded. Multivariable analyses adjusted for detailed clinical characteristics and for individual laboratory. RESULTS: Stents were associated with a significant reduction in in-hospital mortality (0.3%) compared with balloon procedures (0.6%; multivariable odds ratio [OR] 0.55; 95% confidence interval [CI] 0.34, 0.89; p = 0.014). The risk of emergency coronary bypass also was reduced by stenting (0.3% vs. 0.7%; multivariable OR 0.47; 95% CI: 0.29, 0.76; p = 0.002). Adjustment for the use of glycoprotein IIb/IIIa inhibitors did not change the results, and the effects of stenting relative to balloon procedures were similar in those procedures with and without glycoprotein IIb/IIIa blockade (p = 0.94). CONCLUSIONS: This study suggests that coronary stenting, compared with balloon procedures, reduces in-hospital mortality, independent of the clinical setting. PMID- 11216970 TI - Nitroglycerin withdrawal increases endothelium-dependent vasomotor response to acetylcholine. AB - OBJECTIVES: We sought to determine whether nitroglycerin (NTG) withdrawal contributes to worsening of endothelial dysfunction and development of the rebound phenomenon during intermittent transdermal NTG therapy. BACKGROUND: Intermittent transdermal NTG therapy is recommended to avoid the development of tolerance. However, this regimen may precipitate worsening angina in the NTG-free interval. METHODS: Twenty patients were randomized to intermittent transdermal NTG (0.6 mg/h; NTG group) or no treatment (control group) five days before angiography. The risk factors for endothelial dysfunction were similar in both groups. After diagnostic angiography, the patients underwent quantitative angiography before and after intracoronary acetylcholine (ACh), 10(-4) mol/liter. Immediately after the morning study, the patch was removed from the NTG group, and 3 h later, the ACh infusion was repeated in both groups. All patients had mild to moderate coronary artery disease (CAD). RESULTS: The diameter of the left anterior descending coronary artery at baseline was 2.0 +/- 0.1 mm in the control group and 2.6 +/- 0.1 mm in the NTG group (p < 0.05). Acetylcholine caused mild vasoconstriction in the control group in the morning and afternoon (2.7 +/- 5.3% and 2.4 +/- 3.9%, respectively; p = NS). The NTG group demonstrated mild vasoconstriction to ACh in the morning (3.2 +/- 2.8%; p = NS vs. control group). After patch removal, there was a significant increase in the magnitude ofvasoconstriction in the NTG group (11.6 +/- 3.9%, p = 0.04 vs. morning constriction). CONCLUSIONS: These results confirm that NTG withdrawal increases the coronary vasomotor response to ACh in patients with mild CAD and suggests that the rebound phenomena may be secondary to the development of endothelial dysfunction after discontinuation of NTG therapy. PMID- 11216971 TI - Platelet inhibitory effect of nitric oxide in the human coronary circulation: impact of endothelial dysfunction. AB - OBJECTIVES: We sought to determine whether coronary vascular nitric oxide (NO) release in vivo modulates platelet activation. BACKGROUND: Nitric oxide modulates vasodilator tone and platelet activity via the cyclic guanosine monophosphate (cGMP) pathway, but whether coronary endothelial dysfunction influences platelet activation in humans is unknown. METHODS: In 26 patients, we measured coronary blood flow, epicardial diameter and coronary sinus platelet cGMP content during intracoronary infusions of acetylcholine (ACH), L-NG monomethyl arginine (L-NMMA) and sodium nitroprusside. RESULTS: Acetylcholine increased platelet cGMP content (p = 0.013), but its magnitude was lower in patients with endothelial dysfunction; thus, patients with epicardial constriction with ACH had a 7 +/- 6%, p = ns change compared with a 32 +/- 13%, p = 0.05 increase in platelet cGMP in those with epicardial dilation. Similarly, patients with atherosclerosis or its risk factors had a smaller increase (9 +/- 6%) compared with those having normal coronary arteries without risk factors (51 +/- 22%, p = 0.019). L-NG monomethyl arginine decreased platelet cGMP content to a greater extent in patients with epicardial dilation with ACH (- 15 +/- 7%, p = 0.06) compared to those with constriction (+5 +/- 6% change, p = 0.5). Sodium nitroprusside produced a similar increase in platelet cGMP content in patients with and without endothelial dysfunction (p = 0.56). The effects of sodium nitroprusside, but not ACH or L NMMA, were reproduced in vitro. CONCLUSIONS: Platelet cGMP levels can be modulated by basal and stimulated release of NO. The platelet inhibitory effect of NO is reduced in patients with endothelial dysfunction, which may explain their increased risk from thrombotic events and the improved survival associated with strategies designed to improve vascular function. PMID- 11216972 TI - Vascular endothelial function and oxidative stress mechanisms in patients with Behcet's syndrome. AB - OBJECTIVES: We sought to test the hypothesis that vascular endothelial function is impaired in Behcet's syndrome and reflects increased levels of oxidative stress. BACKGROUND: Behcet's syndrome is a multisystem inflammatory disorder commonly complicated by vascular thrombosis and arterial aneurysm formation. The precise mechanisms underlying vascular disease in Behcet's syndrome are not known. METHODS: We studied 19 patients with Behcet's syndrome (18 to 50 years old, 9 men) and 21 healthy volunteers (18 to 50 years old, 10 men). Brachial artery flow-mediated dilation (endothelium-dependent), and nitroglycerin (NTG) induced dilation (endothelium-independent) were measured. To investigate oxidative stress mechanisms, vascular studies were repeated 1 h after administration of vitamin C (1 g, intravenous) in 12 patients and 12 control subjects. RESULTS: Flow-mediated dilation was reduced in patients with Behcet's syndrome as compared with control subjects (0.7 +/- 0.9% vs. 5.7 +/- 0.9%, p = 0.001). In contrast, there were no significant differences in the brachial artery diameter (4.2 +/- 0.2 vs. 4.0 +/- 0.2 mm, p = 0.47) or NTG-induced dilation (19.7 +/- 1.9% vs. 19.7 +/- 1.2%, p = 0.98). In regression analysis, Behcet's syndrome was associated with impaired flow-mediated dilation independent of age, gender, brachial artery diameter, blood pressure, cholesterol and glucose. Vitamin C increased flow-mediated dilation in Behcet's syndrome (0.2 +/- 0.7% to 3.5 +/- 1.0%, p = 0.002), but not in control subjects (4.3 +/- 0.6% to 4.7 +/- 0.4%, p = 0.51). In both groups, NTG-induced dilation and brachial artery diameter were unchanged after vitamin C treatment. CONCLUSIONS: Vascular endothelial function is impaired in Behcet's syndrome and can be rapidly improved by vitamin C treatment. Our results support a role for oxidative stress in the pathophysiology of Behcet's syndrome and provide a rationale for therapeutic studies aimed at reducing vascular complications in this disorder. PMID- 11216973 TI - Early mortality and morbidity of bilateral versus single internal thoracic artery revascularization: propensity and risk modeling. AB - OBJECTIVES: We examined whether bilateral internal thoracic artery (BITA) revascularization is associated with any increased in-hospital mortality and complications compared with single internal thoracic artery (SITA) revascularization. BACKGROUND: Despite proven long-term benefits, BITA revascularization has been slow to be adopted because of fear of increased early morbidity. METHODS: We evaluated 1,697 consecutive patients undergoing BITA (n = 867) or SITA (n = 830) revascularization. We used propensity score analyses and adjusted risk models to address differences between arms. RESULTS: There were 20 (2.3%) deaths in the BITA group versus 26 (3.1%) in the SITA group (odds ratio 0.73, p = 0.30). Propensity analysis identified several parameters that affected the decision to use BITA. Adjusting for propensity score and all potential risk factors, the odds ratio for death with BITA versus SITA was practically 1. Bilateral internal thoracic artery revascularization did not increase the number of in-hospital complications with the possible exception of deep sternal wound infections (11 [1.3%] vs. 3 [0.4%], p = 0.057). In multivariate modeling BITA increased the risk of deep sternal wound infections only in emergent cases and in older patients; the excess risk was negligible among 1,206 patients (71.1% of total) who did not have emergent revascularization and were < or =70 years old (risk difference 0.3%, p = 0.74). There was no difference in length of stay after adjustment for propensity factors (mean 11.3 vs. 11.7 days, p = 0.66). CONCLUSIONS: Bilateral internal thoracic artery revascularization grafting confers no increased risk for early death and does not prolong hospital stay. The small increase in the risk of deep sternal wound infections does not affect the majority of patients. PMID- 11216974 TI - Coronary artery revascularization in patients with sustained ventricular arrhythmias in the chronic phase of a myocardial infarction: effects on the electrophysiologic substrate and outcome. AB - OBJECTIVES: The objective of this study was to analyze the influence of coronary artery revascularization in patients with ventricular arrhythmias. BACKGROUND: Coronary artery revascularization is an effective treatment for myocardial ischemia; however, its effect on ventricular arrhythmias not related to an acute ischemic event has not been carefully studied. METHODS: Sixty-four patients (58 men, mean age 65 +/- 8 years old) with prior myocardial infarction, spontaneous ventricular arrhythmias not related to an acute ischemic event (55 ventricular tachycardia, 9 ventricular fibrillation) and coronary lesions requiring revascularization were studied prospectively. Electrophysiological study was performed before and after revascularization, and events during follow-up were analyzed. RESULTS: At initial study 61 patients were inducible into sustained ventricular arrhythmias. After revascularization, in 62 survivors, 52 out of 59 patients previously inducible were still inducible (group A), and 10 patients were noninducible (group B). No differences were found in clinical, hemodynamic, therapeutic and electrophysiological characteristics between both groups. During 32 +/- 26 months follow-up, 28/52 patients in group A (54%) and 4/10 patients in group B (40%) had arrhythmic events (p = 0.46). An ejection fraction <30% predicted recurrent arrhythmic events (p = 0.02), but not the presence of demonstrable ischemia before revascularization (p = 0.42), amiodarone (p = 0.69) or beta-adrenergic blocking agent therapy (p = 0.53). Total mortality was 10% in both groups. CONCLUSIONS: In patients with ventricular arrhythmias in the chronic phase of myocardial infarction, probability of recurrence is high despite coronary artery revascularization, but mortality is low if combined with appropriate antiarrhythmic therapy. Recurrences are related to the presence of a low ejection fraction but not to demonstrable ischemia before revascularization, amiodarone or beta-blocker therapy nor are they the results of electrophysiological testing after revascularization. PMID- 11216975 TI - Different patterns of atrial activation in idiopathic atrial fibrillation: simultaneous multisite atrial mapping in patients with paroxysmal and chronic atrial fibrillation. AB - OBJECTIVES: We aimed to evaluate: 1) the behavior of electrical activity simultaneously in different atrial regions during atrial fibrillation (AF); 2) the difference of atrial activation between paroxysmal and chronic AF; 3) the atrial refractoriness dispersion; and 4) the correlation between the effective refractory periods (ERPs) and the FF intervals. BACKGROUND: Little data exist on the electrophysiologic characteristics of the different atrial regions in patients with AF. A more detailed knowledge of the electrical activity during AF may provide further insights to improve treatment of AF. METHODS: Right and left atria were extensively mapped in 30 patients with idiopathic AF (18 paroxysmal and 12 chronic). In different atrial locations, we analyzed 1) the FF interval duration; and 2) the grade of organization and, in case of organized electrical activity, the direction of atrial activation. Furthermore, in patients with paroxysmal AF, we determined the atrial ERP, evaluated the ERP dispersion and assessed the presence of a correlation between the ERPs and the FF intervals. RESULTS: In patients with chronic AF, we observed a shortening of the FF intervals and a greater prevalence of disorganized activity in all the atrial sites examined. In patients with paroxysmal AF, a significant dispersion of refractoriness was observed. The right lateral wall showed longer FF intervals and more organized atrial activity and, unexpectedly, the shortest mean ERPs. In contrast, the septal area showed shorter FF intervals, greater disorganization and the longest mean ERPs. CONCLUSIONS: Electrical activity during AF showed a significant spatial inhomogeneity, which was more evident in patients with paroxysmal AF. The mean FF intervals did not correlate with the mean ERPs. PMID- 11216976 TI - Single oral loading dose of propafenone for pharmacological cardioversion of recent-onset atrial fibrillation. AB - The efficacy and safety of the single dose oral loading regimen of propafenone for pharmacological cardioversion of recent-onset atrial fibrillation (AFib) was evaluated by analyzing the trials on the subject identified through a comprehensive literature search. Most of the trials used a single dose of 600 mg for oral loading. The success rates ranged from 56% to 83%, depending on the duration of AFib and follow-up after drug administration. The conversion time ranged from 110 +/- 59 to 287 +/- 352 min, depending on the duration of observation after drug administration. The single dose oral loading regimen of propafenone was significantly more efficacious than placebo in the first 8 h after administration but not at 24 h. Compared with the intravenous regimen, the oral regimen resulted in fewer conversions in the first 2 h, but both regimens were equally efficacious afterward. The oral propafenone regimen was as efficacious as the single dose oral loading regimen of flecainide but was superior to those of quinidine and amiodarone. The adverse effects reported were transient arrhythmia, reversible QRS-complex widening, transient hypotension and mild noncardiac side effects. The transient arrhythmias were chiefly at the time of conversion and included appearance of atrial flutter, bradycardia, pauses and junctional rhythm. No life-threatening proarrhythmic adverse effects were reported. The single oral loading dose of propafenone appears to be highly effective for conversion of recent-onset AFib, with a relatively rapid effect within 2 to 3 h and freedom from serious adverse effects. PMID- 11216977 TI - Efficacy and safety of out-of-hospital self-administered single-dose oral drug treatment in the management of infrequent, well-tolerated paroxysmal supraventricular tachycardia. AB - OBJECTIVES: We tested the efficacy of two drug treatments, flecainide (F) and the combination ofdiltiazem and propranolol (D/P), administered as a single oral dose for termination of the arrhythmic episodes. BACKGROUND: Both prophylactic drug therapy and catheter ablation are questionable as first-line treatments in patients with infrequent and well-tolerated episodes of paroxysmal supraventricular tachycardia (SVT). METHODS: Among 42 eligible patients (13% of all screened for SVT) with infrequent (< or =5/year), well-tolerated and long lasting episodes, 37 were enrolled and 33 had SVT inducible during electrophysiological study. In the latter, three treatments (placebo, F, and D/P) were administered in a random order 5 min after SVT induction on three different days. RESULTS: Conversion to sinus rhythm occurred within 2 h in 52%, 61%, and 94% of patients on placebo, F and D/P, respectively (p < 0.001). The conversion time was shorter after D/P (32 +/- 22 min) than after placebo (77 +/- 42 min, p < 0.001) or F (74 +/- 37 min, p < 0.001). Four patients (1 placebo, 1 D/P, and 2 F) had hypotension and four (3 D/P and 1 F) a sinus rate <50 beats/min following SVT interruption. Patients were discharged on a single oral dose of the most effective drug treatment (F or D/P) at time of acute testing. Twenty-six patients were discharged on D/P and five on F. During 17 +/- 12 months follow-up, the treatment was successful in 81% of D/P patients and in 80% of F patients, as all the arrhythmic episodes were interrupted out-of-hospital within 2 h. In the remaining patients, a failure occurred during one or more episodes because of drug ineffectiveness or drug unavailability. One patient had syncope after D/P ingestion. During follow-up, the percentage of patients calling for emergency room assistance was significantly reduced as compared to the year before enrollment (9% vs. 100%, p < 0.0001). CONCLUSIONS: The episodic treatment with oral D/P and F, as assessed during acute testing, appears effective in the management of selected patients with SVT. This therapeutic strategy minimizes the need for emergency room admissions during tachycardia recurrences. PMID- 11216978 TI - Lack of efficacy of atenolol for the prevention of neurally mediated syncope in a highly symptomatic population: a prospective, double-blind, randomized and placebo-controlled study. AB - OBJECTIVES: This study was designed to evaluate the efficacy of atenolol for the long-term management of patients with vasovagal syncope. The primary hypothesis was that atenolol is not superior to placebo for the treatment of vasovagal syncope. BACKGROUND: There is no definitive well-controlled analysis of the efficacy of beta-adrenergic blocking agents in patients with recurrent vasovagal syncope. METHODS: This is a prospective, randomized, double-blind, placebo controlled study. Fifty patients with recurrent vasovagal syncope were included (at least two episodes in the last year). A baseline tilt test was performed. Twenty patients (40%) had a positive tilt test. Intravenous atenolol prevented a second positive tilt in five patients. The patients were randomized to receive either atenolol or a placebo (26 patients atenolol 50 mg/day, 24 patients placebo). The follow-up procedure lasted one year. The primary end point of the study was the time to first recurrence of syncope. RESULTS: In the intention-to treat analysis, the group treated with atenolol had a similar number of patients with recurrent syncopal episodes as the placebo group. The Kaplan-Meier actuarial estimates of time to first syncopal recurrence showed that the probability of remaining free of syncope drops similarly in both groups and that there was no statistical difference between both curves (patients treated with atenolol vs. the placebo) with a log-rank test p value of 0.4517. CONCLUSIONS: The recurrence of neurocardiogenic syncope in highly symptomatic patients treated with atenolol is similar to that of patients treated with placebo. PMID- 11216979 TI - Can we assess the efficacy of therapy in neurocardiogenic syncope? PMID- 11216980 TI - A founder mutation of the potassium channel KCNQ1 in long QT syndrome: implications for estimation of disease prevalence and molecular diagnostics. AB - OBJECTIVES: We took advantage of the genetic isolate of Finns to characterize a common long QT syndrome (LQTS) mutation, and to estimate the prevalence of LQTS. BACKGROUND: The LQTS is caused by mutations in different ion channel genes, which vary in their molecular nature from family to family. METHODS: The potassium channel gene KCNQ1 was sequenced in two unrelated Finnish patients with Jervell and Lange-Nielsen syndrome (JLNS), followed by genotyping of 114 LQTS probands and their available family members. The functional properties of the mutation were studied using a whole-cell patch-damp technique. RESULTS: We identified a novel missense mutation (G589D or KCNQ1-Fin) in the C-terminus of the KCNQ1 subunit. The voltage threshold of activation for the KCNQ1-Fin channel was markedly increased compared to the wild-type channel. This mutation was present in homozygous form in two siblings with JLNS, and in heterozygous form in 34 of 114 probands with Romano-Ward syndrome (RWS) and 282 family members. The mean (+/ SD) rate-corrected QT intervals of the heterozygous subjects (n = 316) and noncarriers (n = 423) were 460 +/- 40 ms and 410 +/- 20 ms (p < 0.001), respectively. CONCLUSIONS: A single missense mutation of the KCNQ1 gene accounts for 30% of Finnish cases with LQTS, and it may be associated with both the RWS and JLNS phenotypes of the syndrome. The relative enrichment of this mutation most likely represents a founder gene effect. These circumstances provide an excellent opportunity to examine how genetic and nongenetic factors modify the LQTS phenotype. PMID- 11216981 TI - Risks and benefits of adding anti-platelet therapy to warfarin among patients with prosthetic heart valves: a meta-analysis. AB - OBJECTIVES: The objective of this study was to compare the effectiveness and safety of adding dipyridamole or aspirin to warfarin among patients with prosthetic heart valves using meta-analytic techniques. BACKGROUND: Patients with prosthetic heart valves are at increased risk for valve thrombosis and arterial thromboembolism. Oral anticoagulation alone, or the addition of antiplatelet drugs, has been used to minimize this risk. An important issue is the effectiveness and safety of the latter strategy. METHODS: A combined MEDLINE and manual search was made for relevant articles from 1966 to November 1999. Standard meta-analysis techniques were used. RESULTS: Ten studies involving 2,199 subjects met the inclusion criteria. Compared with anticoagulation alone, the addition of an antiplatelet agent reduced the risk of thromboembolic events (odds ratio [OR]: 0.41, p < 0.001) and total mortality (OR: 0.49, p < 0.001). The risk of major bleeding was increased when antiplatelet agents were added (OR: 1.50, p = 0.033). For major bleeding, the comparison of trials performed before and after 1990 (OR: 2.23 and 0.88, respectively) showed that the chi-square test for heterogeneity was significant (p = 0.025). The latter trials used low-dose aspirin, suggesting that the risk of bleeding may be lower with contemporary low-dose (100 mg daily) aspirin. CONCLUSIONS: Adding antiplatelet therapy, especially low-dose aspirin, to warfarin decreases the risk of systemic embolism or death among patients with prosthetic heart valves. The risk of major bleeding is slightly increased with antiplatelet therapy. Nonetheless, the risk of bleeding appears to have diminished with the lower doses of aspirin used in the more recent trials, resulting in a favorable risk-to-benefit profile. PMID- 11216982 TI - Reoperation for prosthetic aortic valve obstruction in the era of echocardiography: trends in diagnostic testing and comparison with surgical findings. AB - OBJECTIVES: We sought to: 1) identify trends in the diagnostic testing of patients with prosthetic aortic valve (AVR) obstruction who undergo reoperation and 2) compare diagnostic test results with pathologic findings at surgery. BACKGROUND: It is unclear whether Doppler transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) have reduced hemodynamic catheterization rates. METHODS: We reviewed 92 consecutive cases ofAVR reoperation at a single center from 1989 to 1998, comparing 49 cases of mechanical AVR obstruction (group A) to 43 cases of bioprosthetic obstruction (group B). Preoperative Doppler TTE was performed in all cases. RESULTS: In group A cases, there was a marginally significant trend towards lower catheterization rates for the Gorlin AVR area, from 36% in 1989 to 1990 to 10% in 1997 to 1998 (p = 0.07), but diagnostic TEE utilization (47% of cases) did not vary. The cause of mechanical AVR obstruction was pannus in 26 cases (53%), mismatch (P-PM) in 19 (39%) and thrombosis in 4 (8%). The mechanism (pannus/thrombus vs. mismatch) was identified in 10% by TTE and 49% by TEE (p < 0.001). In group B cases, hemodynamic catheterization rates (21%) and diagnostic TEE utilization (21%) did not vary with time. Obstruction was caused by structural degeneration in 37 cases (86%), thrombosis in 3 (7%), mismatch in 2 (5%) and pannus in 1 (2%). The mechanism was correctly identified in 63% by TTE and in 81% by TEE (p = 0.18). CONCLUSIONS: Doppler TTE is the primary means to diagnose AVR obstruction; hemodynamic catheterization is not routinely needed. In unselected patients with mechanical AVR obstruction, TEE differentiation of pannus or thrombus from mismatch is challenging. PMID- 11216983 TI - Outcomes of late atrial tachyarrhythmias in adults after the Fontan operation. AB - OBJECTIVES: The purpose of this study was to compare the clinical and echocardiographic features of adults who developed atrial tachyarrhythmias (ATs) late after a Fontan procedure with those who have remained free of arrhythmias. BACKGROUND: Atrial tachyarrhythmias are a frequent complication of the Fontan operation. However, the outcomes in adult patients with AT who have had the Fontan operation have not been well defined. METHODS: We reviewed the outcomes of 94 consecutive patients who underwent the Fontan operation between 1977 and 1994 and were followed as adults at the University of Toronto Congenital Cardiac Centre for Adults. Sixty patients had an atriopulmonary connection, 21 patients had an atrioventricular connection, and 13 patients received a lateral tunnel connection. RESULTS: Thirty-nine patients (41%) had sustained AT (atrial fibrillation, atrial flutter or supraventricular tachycardia) after their Fontan procedure. Compared with patients who did not develop AT, those who did were more likely to develop heart failure (46% vs. 13%, p = 0.003) and right atrial thrombus (31% vs. 4%, p = 0.006), exhibit left atrial enlargement (mean [+/-SD] diameter: 44 +/- 10 vs. 37 +/- 9 mm, p = 0.002), exhibit right atrial enlargement (mean [+/-SD] volume: 139 +/- 149 vs. 76 +/- 54 ml, p = 0.040) and have moderate to-severe systemic valve regurgitation (31% vs. 7%, p = 0.010). The mean survival time was not significantly different between the arrhythmia group and the arrhythmia-free group (21.2 +/- 1.3 and 18.0 +/- 0.7 years, respectively; p = 0.900). CONCLUSIONS: Systemic atrioventricular valvular regurgitation and biatrial enlargement are commonly observed in patients who develop AT after the Fontan procedure. These patients are more likely to develop right atrial thrombus and heart failure. PMID- 11216984 TI - Major coronary artery anomalies in a pediatric population: incidence and clinical importance. AB - OBJECTIVES: We sought to prospectively determine the incidence and clinical significance of major coronary artery anomalies in asymptomatic children using transthoracic two-dimensional echocardiography. BACKGROUND: Anomalous origins of the left main coronary artery (ALMCA) from the right sinus of Valsalva or anomalous origins the right coronary artery (ARCA) from the left sinus are rarely diagnosed in children and can cause sudden death, especially in young athletes. Because most patients are asymptomatic, the diagnosis is often made post mortem. No study to date has prospectively identified anomalous coronary arteries in asymptomatic children in the general population. METHODS: After serendipitously identifying an index case with ALMCA, we examined proximal coronary artery anatomy in children with otherwise anatomically normal hearts who were referred for echocardiography. In those diagnosed with ALMCA or ARCA, we performed further tests. RESULTS: Within a three-year period, echocardiograms were obtained in 2,388 children and adolescents. Four children (0.17%) were identified with anomalous origin of their coronary arteries, and angiograms, exercise perfusion studies and/or stress tests were then performed. One ARCA patient had decreased perfusion in the right coronary artery (RCA) perfusion area and showed ventricular ectopy on electrocardiogram (ECG) at rest that diminished but did not resolve with exercise. A second patient with ALMCA had atrial tachycardia immediately after exercise, with inferior and lateral ischemic changes on ECG and frequent junctional and/or ventricular premature complexes both at rest and recovery. CONCLUSIONS: This study demonstrates that although anomalous origins of coronary arteries are rare in asymptomatic children, the prevalence is greater than that found in other prospective studies. Ischemia can occur with both ALMCA and ARCA even though patients remain asymptomatic. Because of the high risk of sudden cardiac death, aggressive surgical management and close follow-up are necessary. PMID- 11216985 TI - Congenital coronary artery anomalies in young patients: new perspectives for timely identification. PMID- 11216986 TI - Acute ethanol exposure fails to elicit preconditioning-like protection in in situ rabbit hearts because of its continued presence during ischemia. AB - OBJECTIVES: Is the timing of exposure critical for ethanol's ability to induce cardioprotection? BACKGROUND: Acute ethanol exposure has been reported to mimic ischemic preconditioning in vitro, but it failed to protect in situ. We hypothesized that these conflicting findings were related to ethanol's presence during ischemia in situ. METHODS: The effect on infarct size (triphenyltetrazolium chloride) of acute ethanol exposure (0.35, 0.7, and 1.4 g/kg IV) 10 min before ischemia was measured in open-chest rabbits after 30 min of regional ischemia and reperfusion and was compared to ethanol's ability to reduce infarct size in isolated hearts in which the timing of ethanol exposure could be varied. RESULTS: Ethanol exposure in situ shortly before ischemia did not reduce infarct size. Moreover, ethanol abolished protection from both ischemic preconditioning and mitochondrial KATP channel activation. In contrast, in buffer-perfused hearts exposed to 10 to 50 mmol/liter ethanol for 5 min followed by washout before ischemia, infarct size was significantly reduced. When ethanol exposure was prolonged until the end of ischemia in isolated hearts, protection was abolished. Conversely, protection was seen when ethanol was infused in situ followed by removal of the heart and perfusion with ethanol-free buffer prior to ischemia in a Langendorff preparation. When 50 min were allowed to metabolize the ethanol prior to ischemia, protection could also be shown in situ. CONCLUSIONS: Ethanol exposure followed by washout or sufficient time to metabolize the alcohol prior to ischemia induces preconditioning-like myocardial protection. However, if present throughout ischemia, ethanol actually blocks all preconditioning-related protection. PMID- 11216987 TI - Hypercholesterolemia impairs myocardial perfusion and permeability: role of oxidative stress and endogenous scavenging activity. AB - OBJECTIVES: We intended to study the effect of hypercholesterolemia (HC) on myocardial perfusion and permeability response to increased cardiac demand. BACKGROUND: Hypercholesterolemia is associated with increased incidence of cardiac events and characterized by impaired coronary vascular function, possibly mediated partly through increased pro-oxidative conditions in plasma and tissue. However, it is yet unclear whether HC is also associated with impaired myocardial perfusion and vascular permeability responses in vivo. METHODS: For 12 weeks pigs were fed a normal, HC or HC diet supplemented daily with antioxidants (HC + AO, 100 IU/kg vitamin E and 1 g vitamin C). Myocardial perfusion and vascular permeability were measured in vivo using electron beam computed tomography before and after cardiac challenge with intravenous adenosine. Plasma and tissue oxidative status was determined ex vivo. RESULTS: Plasma cholesterol increased in all cholesterol-fed pigs but was associated with increased markers of oxidative stress only in HC pigs. Myocardial perfusion increased in response to adenosine in normal and HC + AO (+37 +/- 13% and +58 +/- 22%, respectively, p < 0.05 vs. baseline) but not in HC, whereas vascular permeability index increased only in HC pigs (+ 92 +/- 25%, p = 0.002). In HC animals, tissue endogenous oxygen radical scavengers and antioxidant vitamins were depleted and LDL oxidizability enhanced, but both were normalized in HC + AO pigs. Myocardial perfusion response was directly, and permeability inversely, associated with plasma and tissue vitamin concentrations. CONCLUSIONS: This study demonstrates that experimental HC is associated with blunted myocardial perfusion and increased vascular permeability responses in vivo to increased cardiac demand, which may be partly mediated by a shift in oxidative status. PMID- 11216988 TI - Efficacy of intracoronary or intravenous VEGF165 in a pig model of chronic myocardial ischemia. AB - OBJECTIVES: We sought to optimize vascular endothelial growth factor (VEGF) treatment for therapeutic angiogenesis in myocardial ischemia, we explored the efficacy of five different regimens. BACKGROUND: Although VEGF165 is one of the most potent pro-angiogenic growth factors, VEGF165 treatment for myocardial ischemia has been hampered by low efficacy and dose-limiting hypotension after systemic or intracoronary delivery. METHODS: This study evaluated the effect of intravenous or intracoronary rhVEGF165 in the presence or absence of nitric oxide (NO) synthase inhibition in a porcine model of chronic myocardial ischemia. Forty two Yorkshire pigs with chronically occluded left circumflex coronary arteries were randomly assigned to receive 10 microg/kg of VEGF165: 1) rapid (40 min) intravenous VEGF165 0.25 microg/kg/min, 2) slow (200 min) intravenous VEGF165 0.05 microg/kg/min, 3) rapid intracoronary VEGF165 0.25 microg/kg/min, 4) rapid intracoronary VEGF165 0.25 microg/kg/min + nitro-L-arginine methyl ester hydrochloride (L-NAME) or 5) rapid vehicle infusion. RESULTS: Intracoronary and intravenous VEGF165 induced hypotension. Intracoronary VEGF-induced hypotension was blocked by L-NAME. Coronary angiography three weeks after treatment showed improvement in collateral index in both intracoronary groups but not the intravenous VEGF165 groups. Likewise, myocardial blood flow and microvascular function in the ischemic territory improved in both intracoronary groups but not in the intravenous groups. Global and regional myocardial function showed no significant improvements in any groups. CONCLUSIONS: Intracoronary infusion of VEGF165 significantly improves blood flow to the ischemic myocardium. Concomitant administration of L-NAME inhibits VEGF-induced hypotension while most likely preserving VEGF-induced angiogenesis. Intravenous infusion of VEGF165 was not effective in augmenting either myocardial flow or function in this model. PMID- 11216989 TI - Quantitative assessment of myocardial perfusion during graded coronary artery stenoses by intravenous myocardial contrast echocardiography. AB - OBJECTIVES: The purpose of this study was to examine whether coronary stenoses of variable severity could be quantitatively assessed by analysis of myocardial perfusion as determined by intravenous (IV) myocardial contrast echocardiography. BACKGROUND: Recently, new contrast agents and imaging technology have been developed that may enable improved assessment of myocardial perfusion by IV contrast injection. METHODS: Variable obstruction of the left anterior descending (LAD) coronary artery in dogs was produced by a screw occluder. Coronary artery flow was measured with a transit time flowmeter during baseline, pharmacological vasodilation, a non-flow-limiting stenosis at rest in conjunction with vasodilation, a flow-limiting stenosis, and total occlusion. Myocardial contrast echocardiography was performed after IV injection of the contrast agent NC 100100. Time-intensity curves were obtained off-line for the LAD risk area and the adjacent left circumflex (LCx) territory, and peak background-subtracted video intensity was determined. Fluorescent microspheres were injected at each intervention for determination of regional myocardial blood flow. RESULTS: During non-flow-limiting stenosis, flow limiting stenosis and total occlusion, LAD/LCx ratios of peak myocardial videointensity and blood flow decreased proportionately. Both LAD/LCx ratios of video intensity and blood flow identified the non-flow-limiting and the flow-limiting stenoses as well as total occlusion of the LAD artery. A significant correlation between LAD/LCx video intensity and blood flow ratios was observed (r = 0.83, p < 0.0001). CONCLUSIONS: The degree of blood flow mismatch between ischemic and normal myocardial regions during graded coronary stenoses can be estimated in the dog by quantitative assessment of myocardial perfusion produced by IV myocardial contrast echocardiography. PMID- 11216990 TI - Validation of a digital color Doppler flow measurement method for pulmonary regurgitant volumes and regurgitant fractions in an in vitro model and in a chronic animal model of postoperative repaired tetralogy of Fallot. AB - OBJECTIVES: The purpose of this study was to validate a digital color Doppler (DCD) automated cardiac flow measurement method for quantifying pulmonary regurgitation (PR) in an in vitro and a chronic animal model of the right ventricular outflow tract of postoperative tetralogy of Fallot (TOF). BACKGROUND: There has been no reliable ultrasound method that can accurately quantitate PR. METHODS: We developed an in vitro model of mild pulmonary stenosis and wide-open PR that mimics the patterns of flow seen in patients with postoperative TOF. Thirteen different forward and regurgitant stroke volumes (RSVs) across the noncircular shaped cross-sectional outflow tract flow area were estimated using the DCD method in two orthogonal planes. In six sheep with surgically created PR, 24 different hemodynamic states with PR strictly quantified by electromagnetic probes were also studied. RESULTS: The RSVs and regurgitant fractions (RFs) obtained by the DCD method using average values from two orthogonal planes correlated well with reference values (RSV: r = 0.99, mean difference = 0.02 +/- 0.39 ml/beat for in vitro model; r = 0.97, mean differences = 1.79 +/- 1.84 ml/beat for animal model, RF: r = 0.98, mean difference = -1.10 +/- 4.34% for in vitro model; r = 0.94, mean difference = 2.73 +/- 6.75% for animal model). However, the DCD method using a single plane had limited accuracy for estimating pulmonary RFs and RSVs. CONCLUSIONS: The DCD method using average values from two orthogonal planes provides accurate estimation of RSVs and RFs and should have clinical importance for serially quantifying PR in patients with postoperative TOF. PMID- 11216991 TI - Mechanism of ischemic mitral regurgitation with segmental left ventricular dysfunction: three-dimensional echocardiographic studies in models of acute and chronic progressive regurgitation. AB - OBJECTIVES: This study aimed to separate proposed mechanisms for segmental ischemic mitral regurgitation (MR), including left ventricular (LV) dysfunction versus geometric distortion by LV dilation, using models of acute and chronic segmental ischemic LV dysfunction evaluated by three-dimensional (3D) echocardiography. BACKGROUND: Dysfunction and dilation-both mechanisms with practical therapeutic implications-are difficult to separate in patients. METHODS: In seven dogs with acute left circumflex (LCX) coronary ligation, LV expansion was initially restricted and then permitted to occur. In seven sheep with LCX branch ligation, LV expansion was also initially limited but became prominent with remodeling over eight weeks. Three-dimensional echo reconstruction quantified mitral apparatus geometry and MR volume. RESULTS: In the acute model, despite LV dysfunction with ejection fraction = 23 +/- 8%, MR was initially trace with limited LV dilation, but it became moderate with subsequent prominent dilation. In the chronic model, MR was also initially trace, but it became moderate over eight weeks as the LV dilated and changed shape. In both models, the only independent predictor of MR volume was increased tethering distance from the papillary muscles (PMs) to the anterior annulus, especially medial and posterior shift of the ischemic medial PM, measured by 3D reconstruction (r2 = 0.75 and 0.86, respectively). Mitral regurgitation volume did not correlate with LV ejection fraction or dP/dt. CONCLUSIONS: Segmental ischemic LV contractile dysfunction without dilation, even in the PM territory, fails to produce important MR. The development of MR relates strongly to changes in the 3D geometry of the mitral apparatus, with implications for approaches to restore a more favorable configuration. PMID- 11216992 TI - Impact directly over the cardiac silhouette is necessary to produce ventricular fibrillation in an experimental model of commotio cordis. AB - OBJECTIVES: In an experimental model of sudden death from chest wall impact (commotio cordis), we sought to define the chest wall areas important in the initiation of ventricular fibrillation (VF). BACKGROUND: Sudden death can result from an innocent chest blow by a baseball or other projectile. Observations in humans suggest that these lethal blows occur over the precordium. However, the precise location of impact relative to the risk of sudden death is unknown. METHODS: Fifteen swine received 178 chest impacts with a regulation baseball delivered at 30 mph at three sites over the cardiac silhouette (i.e., directly over the center, base or apex of the left ventricle [LV]) and four noncardiac sites on the left and right chest wall. Chest blows were gated to the vulnerable portion of the cardiac cycle for the induction of VF. RESULTS: Only chest impacts directly over the heart triggered VF (12 of 78: 15% vs. 0 of 100 for noncardiac sites: p < 0.0001). Blows over the center of the heart (7 of 23; 30%) were more likely to initiate VF than impacts at other precordial sites (5 of 55; 9%, p = 0.02). Peak LV pressures generated instantaneously by the chest impact were directly related to the risk of VF (p < 0.0006). CONCLUSIONS: For nonpenetrating, low-energy chest blows to cause sudden death, impact must occur directly over the heart. Initiation of VF may be mediated by an abrupt and substantial increase in intracardiac pressure. Prevention of sudden death from chest blows during sports requires that protective equipment be designed to cover all portions of the chest wall that overlie the heart, even during body movements and positional changes that may occur with athletic activities. PMID- 11216993 TI - Adventitial remodeling after angioplasty is associated with expression of tenascin mRNA by adventitial myofibroblasts. AB - OBJECTIVES: The purpose of this study was to determine the temporospatial expression of tenascin-C (TnC) in balloon-injured rat and porcine arteries. BACKGROUND: Recent studies suggest that cell migration, in addition to cell proliferation, is a critical component of neointima formation after vascular injury. We have previously shown that adventitial myofibroblasts synthesize growth factors that contribute to the formation of neointima after arterial injury. We have also shown that the extracellular matrix protein, TnC, regulates cell migration. Consequently, we investigated the temporospatial expression of TnC by myofibroblasts after vascular injury. METHODS: In situ hybridization and immunohistochemistry were used to investigate the temporospatial expression of TnC in injured arteries. Northern and Western blots were used to determine the in vitro expression of TnC. RESULTS: In situ hybridization revealed that the major site of TnC expression early after vascular injury was the adventitial myofibroblasts. Immunohistochemical staining demonstrated that TnC expression began in adventitial myofibroblasts three days after injury. Tenascin-C expression, however, did not persist in this region. Rather, it moved progressively across the vascular wall toward the luminal surface. By one week, TnC expression reached the developing neointima. In vitro, myofibroblasts did not express TnC mRNA under basal conditions. In contrast, angiotensin II and PDGF-BB, factors that have been implicated in remodeling of balloon-injured arteries, markedly upregulated TnC mRNA. CONCLUSIONS: Tenascin-C is expressed in response to balloon injury. Tenascin-C expression begins with adventitial myofibroblasts. Over a period of 7 to 14 days, expression moves progressively across the vessel wall to the neointima. We hypothesize that adventitial myofibroblasts are actively involved in the formation of neointima and that TnC facilitates migration of these cells during adventitial remodeling. PMID- 11216994 TI - Prevention of aortic and cardiac fibrosis by spironolactone in old normotensive rats. AB - OBJECTIVES: Because the synthesis of aldosterone is mainly modulated by angiotensin II through type I receptor stimulation and because converting enzyme inhibition (CEI) does not modify aortic extracellular matrix in old normotensive rats, the aim of the present study was to determine whether inhibition of aldosterone formation was able to prevent aortic fibrosis in old Sprague-Dawley normotensive rats. BACKGROUND: We have previously shown that long-term aldosterone antagonism prevents the age-related increase in aortic collagen accumulation in young spontaneously hypertensive rats, independent of blood pressure changes. In contrast, we reported that the positive effects of CEI in the prevention of aortic collagen accumulation were related to the inhibition of angiotensin II actions on angiotensin II type I receptors. METHODS: For this purpose, we studied the histomorphometric and stiffness (echo-tracking technique) changes of an eight-week treatment with the aldosterone antagonist spironolactone by comparison with placebo. RESULTS: At the end of treatment, spironolactone in conscious animals did not change intra-arterial blood pressure, aortic and carotid wall thickness, and cardiac weight. Cardiac collagen density and, to a lesser extent, carotid collagen and elastin densities and contents were significantly decreased in association with an increase of carotid distensibility. CONCLUSIONS: These results show that in old normotensive rats, spironolactone can markedly prevent cardiac and, to a lesser extent, arterial fibrosis and improve arterial stiffness, despite a lack of hypotensive effect. PMID- 11216995 TI - Soluble substances released from postischemic reperfused rat hearts reduce calcium transient and contractility by blocking the L-type calcium channel. AB - OBJECTIVES: This study was designed to investigate the effects of cardiodepressant substances released from postischemic myocardial tissue on myocardial calcium-regulating pathways. BACKGROUND: We have recently reported that new cardiodepressant substances are released from isolated hearts during reperfusion after myocardial ischemia. METHODS: After 10 min of global ischemia, isolated rat hearts were reperfused, and the coronary effluent was collected for 30 s. We tested the effects of the postischemic coronary effluent on cell contraction, Ca2+ transients and Ca2+ currents of isolated rat cardiomyocytes by applying fluorescence microscopy and the whole-cell, voltage-clamp technique. Changes in intracellular phosphorylation mechanisms were studied by measuring tissue concentrations of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), as well as activities of cAMP-dependent protein kinase (cAMP-dPK) and protein kinase C (PKC). RESULTS: The postischemic coronary effluent, diluted with experimental buffer, caused a concentration-dependent reduction of cell shortening and Ca2+ transient in the field-stimulated isolated cardiomyocytes of rats, as well as a reduction in peak L-type Ca2+ current in voltage-clamped cardiomyocytes. The current reduction resulted from reduced maximal conductance--not from changes in voltage- and time-dependent gating of the L-type Ca2+ channel. The postischemic coronary effluent modified neither the tissue concentrations of cAMP or cGMP nor the activities of cAMP-dPK and PKC. However, the effluent completely eliminated the activation of glycogen phosphorylase after beta-adrenergic stimulation. CONCLUSIONS: Negative inotropic substances released from isolated postischemic hearts reduce Ca2+ transient and cell contraction through cAMP-independent and cGMP-independent blockage of L-type Ca2+ channels. PMID- 11216996 TI - Redox regulation of MAPK pathways and cardiac hypertrophy in adult rat cardiac myocyte. AB - OBJECTIVES: We analyzed the regulatory function of reactive oxygen species (ROS) on the hypertrophic signaling in adult rat cardiac myocytes: BACKGROUND: The ROS regulate mitogenic signal transduction in various cell types. In neonatal rat cardiac myocyte, antioxidants have been shown to inhibit cardiac hypertrophy, and ROS are suggested to modulate the hypertrophic signaling. However, the conclusion may not reflect the situation of mature heart, because of the different natures between neonatal and adult cardiac myocytes. METHODS: Cultured adult rat cardiac myocytes were stimulated with endothelin-1 (ET-1) or phenylephrine (PE), and intracellular ROS levels, the activities of mitogen-activated protein kinases (MAPKs; ERK, p38, and JNK), and 3H-phenylalanine incorporation were examined. We also examined the effects of antioxidant pretreatment of myocytes on MAPK activities and cardiac hypertrophy to analyze the modulatory function of redox state on MAPK-mediated hypertrophic signaling. RESULTS: The ROS levels in ET-1- or PE-stimulated myocytes were maximally increased at 5 min after stimulation. The origin of ROS appears to be from NADH/NADPH oxidase, because the increase in ROS was suppressed by pretreatment of myocytes with NADH/NADPH oxidase inhibitor diphenyleneiodonium. Extracellular signal-regulated kinase (ERK) activity was increased by the stimulation of ET-1 or PE. In contrast, p38 and c-Jun-N-terminal protein kinase (JNK) activities did not change after these stimulations. Antioxidant treatment of myocytes suppressed the increase in ROS and blocked ERK activation and the subsequent cardiac hypertrophy induced by these stimuli. CONCLUSIONS: These data demonstrate that ROS mediate signal transduction of cardiac hypertrophy induced by ET-1 or PE in adult rat cardiac myocytes. PMID- 11216998 TI - President's page: patient satisfaction: a personal perspective. PMID- 11216997 TI - The family under attack. PMID- 11216999 TI - Vascular effect of insulin in endothelial dysfunction. PMID- 11217000 TI - Electron beam computed tomography in the diagnosis of obstructive coronary artery disease. PMID- 11217001 TI - Use of teleoptometry to evaluate acceptability of rigid gas-permeable contact lens fits. AB - BACKGROUND: Teleoptometry involves the transmission of digitized optometric information from a remote site for analysis by an expert. This project assessed computer compression of video data showing contact lens fitting relationships and the transmission of these data to a specialist for evaluation METHODS: Fifty-five sets of video clips showing dynamic fluorescein patterns of rigid gas-permeable lens fits, topographic corneal maps, and basic information on lens parameters were evaluated-live and again after digitization and electronic compression-by a contact lens specialist. The evaluator was asked to determine whether lens fit was acceptable and, if not, how the lens parameters should be changed. RESULTS: Comparison of lens evaluations made live versus compressed showed agreement on fit acceptability for approximately 80% of the subject/lens combinations. When the evaluator concluded for both presentations that the lens was unacceptable, the same change in lens parameters was recommended 67% of the time. DISCUSSION: Agreement for the majority of live and compressed video observations suggests that teleoptometric consultation on contact lens fitting is feasible. When technology advances to the point at which large files can be sent quickly via the Internet, it is likely the practice of transmitting video clips and other information to obtain fitting assistance will become commonplace. PMID- 11217002 TI - Effect of near-vision addition lenses on the accuracy of the accommodative response. AB - BACKGROUND: Addition lenses (adds) are frequently used to increase the accuracy of the near-vision focusing response, and may also play a role in the prevention or retardation of refractive error development. However, following the introduction of such a lens, if the accommodative response is reduced by an amount equal to the magnitude of the near add, then the resulting accommodative error (and degree of retinal defocus) would remain unchanged. METHODS: This study measured the accommodative response in 28 subjects while they viewed a near target binocularly, either through their distance refractive correction alone or this correction combined with a +0.75 D, +1.50 D, +2.00 D, or +2.50 D near add. RESULTS: The mean findings demonstrated a small (0.03 D) lead of accommodation to the near target through the distance correction, and monotonically increasing leads of accommodation with larger adds. Further, the additional lens power required to reduce the accommodative error to zero correlated significantly with the initial accommodative error. CONCLUSIONS: Near addition lenses may actually increase the degree of retinai defocus for individuals who manifest small accommodative errors. PMID- 11217003 TI - Optic disk edema in a patient with non-Hodgkin's lymphoma: is there a metastasis to the brain? AB - BACKGROUND: The manifestation of bilateral disk swelling raises the suspicion of papilledema and mandates that an etiology for increased intracranial pressure be discovered. This case report will present the manifestations and treatment of non Hodgkin's lymphoma and review the differential diagnoses of bilateral disk edema. CASE REPORT: A 51-year-old black man manifested symptoms of dizziness and intermittent loss of vision in the left eye for one week. Dilated funduscopy revealed early left optic disk edema; edema of the right optic nerve head was questionable. The patient had pulmonary nodules noted on a recent chest x-ray that were thought to be cancerous; this raised the suspicion of a metastasis to the brain or orbit. The patient did not return until about 10 weeks later, at which time he presented with a history significant for newly-diagnosed intermediate-grade non-Hodgkin's lymphoma. He had begun chemotherapy one month before the second examination at our clinic; methotrexate therapy for CNS metastasis had been provided at the time of the spinal taps. At the second visit, there was marked progression of the swelling of the left optic disk and mild swelling of the right disk. At the third visit, six weeks later, the disk edema had improved remarkably. The patient's disk swelling resolved completely by the end of his six months of chemotherapy. CONCLUSION: This is a unique presentation of a patient at high risk for brain metastasis, in which laboratory and radiologic studies failed to provide adequate supportive evidence for the conclusions drawn from clinic observations. Bilateral disk edema in a patient with a history of non-Hodgkin's lymphoma is strongly suggestive of a metastatic tumor to the brain causing increased intracranial pressure. PMID- 11217004 TI - Contact dermatitis. AB - BACKGROUND: Anatomically, the eyelid can be divided microscopically into (1) skin, which is made up of epidermis and dermis; (2) submucosa (3) muscular layer; (4) submuscular layer (dense connective tissue); (5) fibrous layer; and (6) palpebral conjunctiva. The thin nature of the eyelid makes it susceptible to inflammation resulting from allergy. Minimum levels of irritants contacting the adnexal area can penetrate the skin to initiate the allergic cascade. Allergic reactions that involve the eye may begin via contact to the skin, but often involve the conjunctiva. Eczema is the general term that describes the superficial inflammatory process involving the epidermis. Contact eczema is characterized by varying elements of epidermal erythema, papules, and vesicles. Allergic dermatoconjunctivitis connotes involvement of both the skin and conjunctiva. CASE REPORT: A 24-year-old man came to the clinic with a red, swollen left eye. Based on the history, the constellation of signs and symptoms (lack of diffuse or focal pain, presence of periorbital and conjunctival edema, absence of fever), and failed resolution after treatment with injectable antibiotics, the diagnosis of type IV delayed hypersensitivity reaction secondary to toxic/chemical exposure was made. Speedy resolution was accomplished using a sequenced therapy, which included oral antihistamines, topical cycloplegics, topical antibiotics, topical steroids, and palliative therapies. CONCLUSION: Optometrists should be familiar with the signs and symptoms of contact eczema and allergic dermatoconjunctivitis. Treatment includes management of the skin and adnexae, as well as the ocular manifestations. PMID- 11217005 TI - Safe exposure times for slit-lamp fundus biomicroscopy with high plus lenses. AB - PURPOSE: The purpose of this study was to calculate the retinal irradiance and maximum permissible exposure time (MPE) using high plus fundus biomicroscopy lenses. METHODS: Four Volk handheld condensing lenses (+78 D, +90 D, Superfield NC, and Super 66) were tested with biomicroscopes from three manufacturers (Nikon, Topcon, and Zeiss) on both high and medium illumination. Using the conservation of radiance theorem, the retinal irradiance was calculated and. with guidelines from the American National Standard Institute (ANSI). the maximum permissible exposure time was determined. RESULTS: The range of MPE time across all lenses and biomicroscopes was from 23 seconds to 74 seconds on high illumination setting. The average MPE times were: for the +78 D, 36 seconds; the Superfield NC, 57 seconds; the Super 66, 32 seconds; and the +90 D, 52 seconds. CONCLUSION: Retinal irradiances and safe exposure times are useful guidelines in both the clinical and academic setting. Fundus biomicroscopy with non-contact high plus condensing lenses produced calculated retinal irradiances and MPE times similar to those of other commonly used ophthalmic equipment. Awareness of the maximum permissible exposure time increases the safety of this valuable technique. PMID- 11217006 TI - Telecommunication-the challenge. PMID- 11217007 TI - Save Your Vision Month 2001 celebration guide. PMID- 11217008 TI - Ophthalmic telemedicine at the Alabama Institute for Deaf and Blind. AB - BACKGROUND: The University of Alabama at Birmingham School of Optometry and the Alabama Institute for Deaf and Blind have collaborated in development of electronic medical records, digital slit-lamp medical imaging, and ocular telemedicine between their two sites. METHODS: The telemedicine link uses the electronic medical record system (EMRS) called PEARL, and digitized slit-lamp images made with an MCV 4000 digital imaging unit attached to a Topcon SL4E slit lamp. RESULTS: These technologies allow remote physician access to medical records as well as remote triage of eye problems using transmitted digital images and telephone consultation. CONCLUSIONS: This implementation strategy can serve as a model for improvement of specialist access to remotely located sites. It is a unique pairing of a school of optometry and a residential institution for people with sensory impairment. PMID- 11217009 TI - A notational analysis of elite tennis strategy. AB - A notational analysis of singles events at all four Grand Slam tournaments between 1997 and 1999 was conducted to determine the influence of the sex of the player and court surface on elite tennis strategy. Rallies of 7.1 +/- 2.0 s in women's singles were significantly longer than those in men's singles (5.2 +/- 1.8 s; P < 0.001). Rallies of 6.3 +/- 1.8 s at the Australian Open, 7.7 +/- 1.7 s at the French Open, 4.3 +/- 1.6 s at Wimbledon and 5.8 +/- 1.9 s at the US Open were recorded. Rallies were significantly longer at the French Open than at any other tournament (P< 0.05) and significantly shorter at Wimbledon than at any other tournament (P< 0.05). In women's singles, 52.8 +/- 12.4% of points were baseline rallies, significantly more than in men's singles (28.6 +/- 19%; P < 0.001). The proportion of baseline rallies played at the French Open (51.9 +/- 14.2% of points) was significantly greater than at the Australian Open (46.6 +/- 12.5%), Wimbledon (19.7 +/- 19.4%) and the US Open (35.4 +/- 19.5%; P < 0.05). The results show that both the sex of the player and surface of the court have a significant influence on the nature of singles tennis at Grand Slam tournaments. PMID- 11217010 TI - Information--movement coupling: implications for the organization of research and practice during acquisition of self-paced extrinsic timing skills. AB - Information--movement coupling is a fundamental concept, integral to theorizing on the coordination of goal-directed activity in ecological psychology. In this paper, we examine the implications of this concept for the design of experimental research and the organization of practice during the acquisition of movement coordination in sport tasks. The task vehicle for our analysis is interceptive actions, in particular self-paced extrinsic timing tasks exemplified by serving in sports such as volleyball. Recent research highlighting the relevance of information--movement coupling for the process of practice in sport is discussed. We conclude that information--movement coupling represents an important principle for the structural organization of research and practice in self-paced extrinsic timing tasks and that further work is required to verify its significance across a range of sport movements. PMID- 11217011 TI - Home advantage in the Winter Olympics (1908-1998). AB - We obtained indices of home advantage, based on the medals won by competing nations, for each event held at the Winter Olympics from 1908 to 1998. These indices were designed to assess home advantage while controlling for nation strength, changes in the number of medals on offer and the performance of 'non hosting' nations. Some evidence of home advantage was found in figure skating, freestyle skiing, ski jumping, alpine skiing and short track speed skating. In contrast, little or no home advantage was observed in ice hockey, Nordic combined, Nordic skiing, bobsled, luge, biathlon or speed skating. When all events were combined, a significant home advantage was observed (P = 0.029), although no significant differences in the extent of home advantage were found between events (P > 0.05). When events were grouped according to whether they were subjectively assessed by judges, significantly greater home advantage was observed in the subjectively assessed events (P = 0.037). This was a reflection of better home performances, suggesting that judges were scoring home competitors disproportionately higher than away competitors. Familiarity with local conditions was shown to have some effect, particularly in alpine skiing, although the bobsled and luge showed little or no advantage over other events. Regression analysis showed that the number of time zones and direction of travel produced no discernible trends or differences in performance. PMID- 11217012 TI - Changes in short-term power output in 10- to 12-year-olds. AB - In this study, we used multi-level regression modelling to assess the influence of age, sex, body size, skinfold thicknesses, maturity, thigh muscle volume and isokinetic leg strength on the development of load- and inertia-adjusted peak (1 s) and mean power (30 s) determined using the Wingate anaerobic test. Fifteen males and 19 females were measured twice, first aged 10.0 +/- 0.3 years and then aged 11.8 +/- 0.3 years. Initial models identified body mass and height as significant explanatory variables (P < 0.05) for peak power and mean power, with an additional age effect for the former. No significant differences between the sexes or maturity effects were observed for either peak or mean power (P > 0.05). The introduction of sum of skinfolds improved the fit of the model and rendered the height term non-significant for both peak and mean power (P> 0.05). An age effect became apparent for mean power. When isokinetic leg strength and thigh muscle volume were entered into the model, the latter exerted a significant effect on both peak and mean power (P< 0.05), whereas isokinetic leg strength was not a significant explanatory variable for either (P> 0.05). In conclusion, thigh muscle volume exerts a positive influence on young people's short-term power output, which is additional to the effects of body mass, sum of skinfolds and age. PMID- 11217013 TI - Kinematic and postural characteristics of sprint running on sloping surfaces. AB - The aim of this study was to identify the kinematic and postural characteristics associated with sprint running on uphill and downhill slopes of 3 degrees and on a horizontal surface. Eight male physical education students were filmed while sprinting maximally on an uphill-downhill platform under each of three conditions: (a) uphill at 3 degrees, (b) downhill at 3 degrees and (c) horizontal. Running speed, step rate, step length, step time, contact time, flight time and selected postural characteristics of the step cycle were analysed. Running speed was 9.2% faster (P < 0.05) during downhill and 3.0% slower (P < 0.05) during uphill compared with horizontal sprint running. During downhill and uphill sprint running, step length was the main contributor to the observed changes in running speed. It increased by 7.1% (P < 0.05) for downhill sprint running and was associated with significant changes in posture at touchdown and take-off. During uphill sprint running, step length decreased by 5.2% (P < 0.05), which was associated with significant changes in posture and reduced flight distance. Given the interaction between the acute changes in step length and posture when sprinting on a sloping surface, our findings suggest that such changes in posture may detract from the specificity of training on such surfaces. The chronic effects of training on such slopes on the kinematics and posture of horizontal sprint running are currently unclear. PMID- 11217014 TI - Hormonal responses to exercise after partial sleep deprivation and after a hypnotic drug-induced sleep. AB - The aim of this study was to determine the hormonal responses, which are dependent on the sleep wake cycle, to strenuous physical exercise. Exercise was performed after different nocturnal regimens: (i) a baseline night preceded by a habituation night; (ii) two nights of partial sleep deprivation caused by a delayed bedtime or by an early awakening; and (iii) two nights of sleep after administration of either a hypnotic compound (10 mg zolpidem) or a placebo. Eight well-trained male endurance athletes with a maximal oxygen uptake of 63.5 +/- 3.8 ml x kg(-1) x min(-1) (mean value +/- s(x)) were selected on the basis of their sleeping habits and their physical training. Polygraphic recordings of EEG showed that both nights with partial sleep loss led to a decrease (P< 0.01) in stage 2 and rapid eye movement sleep. A delayed bedtime also led to a decrease (P < 0.05) in stage 1 sleep. Zolpidem had no effect on the different stages of sleep. During the afternoon after an experimental night, exercise was performed on a cycle ergometer. After a 10-min warm-up, the participants performed 30 min steady-state cycling at 75% VO(2-max) followed by a progressively increased workload until exhaustion. The recovery period lasted 30 min. Plasma growth hormone, prolactin, cortisol, catecholamine and lactate concentrations were measured at rest, during exercise and after recovery. The concentration of plasma growth hormone and catecholamine were not affected by partial sleep deprivation, whereas that of plasma prolactin was higher (P < 0.05) during the trial after an early awakening. Plasma cortisol was lower (P < 0.05) during recovery after both sleep deprivation conditions. Blood lactate was higher (P < 0.05) during submaximal exercise performed after both a delayed bedtime and an early awakening. Zolpidem-induced sleep did not affect the hormonal and metabolic responses to subsequent exercise. Our results demonstrate only minor alterations in the hormonal responses to exercise after partial sleep deprivation. PMID- 11217015 TI - Effects of external loading on power output in a squat jump on a force platform: a comparison between strength and power athletes and sedentary individuals. AB - The aim of this study was to determine the effects of external loading on power output during a squat jump on a force platform in athletes specializing in strength and power events (6 elite weight-lifters and 16 volleyball players) and in 20 sedentary individuals. Instantaneous power was computed from time-force curves during vertical jumps with and without an external load (0, 5 or 10 kg worn in a special vest). The jumps were performed from a squat position, without lower limb counter-movement or an arm swing. Peak instantaneous power corresponded to the highest value of instantaneous power during jumping. Average power throughout the push phase of the jump was also calculated. A two-way analysis of variance showed significant interactions between the load and group effects for peak instantaneous power (P< 0.01) and average power (P< 0.001). Peak instantaneous power decreased significantly in sedentary individuals when moderate external loads were added. The peak instantaneous power at 0 kg was greater than that at 5 and 10 kg in the sedentary individuals. In contrast, peak instantaneous power was independent of load in the strength and power athletes. Mean power at 0 kg was significantly lower than at 5 kg in the athletes; at 0 kg it was significantly higher than at 10 kg in the sedentary males and at 5 and 10 kg in the sedentary females. In all groups, the force corresponding to peak instantaneous power increased and the velocity corresponding to peak instantaneous power decreased with external loading. The present results suggest that the effects of external loading on peak instantaneous power are not significant in strength and power athletes provided that the loads do not prevent peak velocity from being higher than the velocity that is optimal for maximal power output. PMID- 11217016 TI - Analytical methods to determine phosphonic and amino acid group-containing pesticides. AB - A comprehensive view on the possibilities of the most recently developed chromatographic methods and emerging techniques in the analysis of pesticides glyphosate, glufosinate, bialaphos and their metabolites is presented. The state of-the-art of the individual pre-treatment steps (extraction, pre-concentration, clean-up, separation, quantification) of the employed analytical methods for this group of chemicals is reviewed. The advantages and drawbacks of the described analytical methods are discussed and the present status and future trends are outlined. PMID- 11217017 TI - Direct separation of the stereoisomers of methoxytetrahydronaphthalene derivatives, new agonist and antagonist ligands for melatonin receptors, by liquid chromatography on cellulose chiral stationary phases. AB - Analytical HPLC methods using derivatized cellulose chiral stationary phases were developed for the direct separation of the stereoisomers of disubstituted tetralin derivatives with two chiral centers, new agonist and antagonist ligands for melatonin receptors. The separations were made using normal-phase methodology with a mobile phase consisting of n-hexane-alcohol (methanol, ethanol, 1-propanol or 2-propanol) in various proportions, and a silica-based cellulose tris-3,5 dimethylphenylcarbamate (Chiralcel OD-H), or tris-methylbenzoate (Chiralcel OJ). The effects of concentration of various aliphatic alcohols in the mobile phase were studied. A better separation was achieved on cellulose carbamate phase compared with the cellulose ester phase. The effects of structural features of the solutes on the discrimination between the stereoisomers were examined. Baseline separation (Rs>1.5) was easily obtained in many cases. PMID- 11217018 TI - Thermosensitive copolymers of N-vinylimidazole as displacers of proteins in immobilised metal affinity chromatography. AB - Synthetic copolymers of N-vinylcaprolactam (VCL) and N-vinylimidazole (VI) were studied as thermosensitive, reusable displacers for immobilised metal affinity chromatography (IMAC) of proteins. The copolymer with weight-average molecular mass of 11700 g/mol prepared by free radical polymerisation at a 9:1 monomer molar ratio was separated into several fractions by IMAC and thermal precipitation. The fraction with an average VI content of 8.5% was most efficient as a reusable displacer for IMAC of ovalbumin, lysozyme and other proteins of egg white on Cu2+-IDA-Sepharose. The displacer exhibited a sharp breakthrough curve and binding capacity of 16-20 mg/ml gel, depending on the flow-rate. The recovery of egg white proteins in the course of displacement chromatography was >95%. The displacer could be removed quantitatively from the protein fractions by thermal precipitation at 48 degrees C. Co-precipitation of lysozyme with the displacer was minimal in the presence of 3% (v/v) acetonitrile, while the lysozyme enzymatic activity in the supernatant was completely retained. Addition of free imidazole to the mobile phase increased the rate of protein desorption and allowed better separation of egg white proteins and the displacer in the course of chromatography. The displacement profile of the egg white extract consisted of three zones with different distributions of individual proteins characterised by SDS-PAGE. Regeneration of the column was easily performed with 0.02 M EDTA in 0.15 M sodium chloride, pH 8.0, followed by washing with distilled water and reloading with Cu2+. The displacer could also be regenerated by thermal precipitation at 48 degrees C and subsequent dialysis against dilute hydrochloric acid (pH 2.5). PMID- 11217019 TI - Monitoring of recombinant human insulin production by narrow-bore reversed-phase high-performance liquid chromatography, high-performance capillary electrophoresis and matrix-assisted laser desorption ionisation time-of-flight mass spectrometry. AB - An analytical scheme for monitoring recombinant human insulin (rhI) production is suggested. The scheme includes high-performance separation micro-techniques (narrow-bore RP-HPLC, HPCE) based on different separation mechanisms and matrix assisted laser desorption ionisation time-of-flight MS, and allows one to obtain unambiguous information about purity and primary structure of all intermediates of the rhI production. The use of this scheme at all production steps provided optimisation of certain technological parameters [conditions for a fusion protein (FP) refolding, temperature and duration of the FP cleavage with trypsin, conditions for carboxypeptidase B digestion of di-ArgB31-B32-insulin] and achievement of a high purity of the end-product. The proposed scheme may be used for solving various problems in monitoring production of other recombinant proteins. PMID- 11217020 TI - Membrane ion-exchange chromatography for process-scale antibody purification. AB - The large-scale production of recombinant monoclonal antibodies demands economical purification processes with high throughputs. The potential for ion exchange membrane adsorbers to replace traditional ion-exchange columns was evaluated. Breakthrough capacities of commercially available cation-exchange membranes were determined as a function of flow-rate and layer number. Due to economic and process restrictions, cation-exchange membranes may not currently be advantageous for process-scale antibody purification in a bind and elute mode. However, anion-exchange membranes in a flow-through mode may provide a reasonable alternative to columns for the removal of low levels of impurities such as DNA, host cell protein, and virus. PMID- 11217021 TI - Purification method for the isolation of monophosphate nucleotides from Champagne wine and their identification by mass spectrometry. AB - Monophosphate nucleotides are difficult to identify in Champagne wine because they are present in small concentrations in a complex mixture. A method for the isolation, separation and identification of reference compounds, which achieved on average 79% recovery (except for cytidine derivatives), was developed and applied to wine. Some monophosphate nucleotides were then isolated from a Champagne wine aged on lees for 8 years, by ultrafiltration followed by a semi preparative HPLC step using a strong anion-exchange column. The fraction obtained was subjected to HPLC in a reversed-phase column to remove the salt previously introduced, before identification of compounds by HPLC coupled to a mass spectrometer. For the first time in wine, 5'-IMP, 5'-AMP, 5'-CMP, 5'-GMP, 5'-UMP and the 3'- and/or 2'-isomers of the four latter compounds were identified by comparing their HPLC and electrospray ionization mass spectrometry data with those of reference nucleotides. PMID- 11217022 TI - Determination of alkylphosphonic acids by microcolumn liquid chromatography with gradient elution coupled on-line with flame photometric detection. AB - Microcolumn liquid chromatography with gradient elution and on-line flame photometric detection has been used for the selective and rapid determination of non-volatile alkylphosphonic acids, which are hydrolysis products of nerve agents, in aqueous samples. A make-up of water was used to maintain stable introduction of the eluent during a gradient run. The detection limits are strongly dependent on quenching, which is determined by the mass flow of methanol in the eluent. Large-volume injections of 100 microl of aqueous solutions of short- and long-chain alkylphosphonic acids resulted in detection limits in the range 6-800 ng/ml. The repeatability of the retention times and analyte response peak area or peak height were 0.7-0.9% and 4-11%, respectively. The method was successfully applied to a local tap water sample and an aqueous soil extract. PMID- 11217023 TI - Reversed-phase high-performance liquid chromatography versus spectrophotometric assay for thimerosal in Cuban recombinant hepatitis B vaccine. AB - A reversed-phase liquid chromatographic method was applied to study the stability of thimerosal in Cuban recombinant hepatitis B vaccine samples stored under different temperature conditions. Salicylic acid was used as internal standard, it allowed one to determine the thimerosal in the presence of its degradation products. Good stability of the preservative was demonstrated in vaccine samples for as long as 6 years. The same results were obtained when the vaccine samples were incubated at 37 and 45 degrees C during 30 days. The results were in compliance with the microbiological test for determining the effectiveness of antimicrobial preservative in these samples. PMID- 11217024 TI - Quantitative determination of marine toxins associated with diarrhetic shellfish poisoning by liquid chromatography coupled with mass spectrometry. AB - Quantitative determination by liquid chromatography (LC) coupled with mass spectrometry (MS) was achieved for the following 10 toxins found in association with diarrhetic shellfish poisoning: okadaic acid (OA), dinophysistoxin-1 (DTX1), 7-O-palmitoylokadaic acid (palOA), 7-O-palmitoyldinophysistoxin-1 (pa1DTX1), pectenotoxin-1 (PTX1), pectenotoxin-2 (PTX2), pectenotoxin-2 seco acid (PTX2SA), pectenotoxin-6 (PTX6), yessotoxin (YTX), and 45-hydroxyyessotoxin (YTXOH). Toxins in 2 g of the adductor muscle or the digestive glands of scallops, Patinopecten yessoensis, were extracted with 18 ml of methanol-water (9:1, v/v), freed of polar contaminants by partition between chloroform and water, and treated by solid-phase extraction on a silica cartridge column. Samples containing YTXOH were purified separately on a buffered reversed-phase column. Chromatographic separation was achieved by the following combinations of columns and mobile phases: a Symmetry C18 column with acetonitrile-0.05% acetic acid (7:3, v/v) for OA, DTX1, PTX6 and PTX2SA; a Develosil ODS column with the same mobile phase for PTX1 and PTX2; a Capcellpak column with methanol-2.5% acetic acid (98:2, v/v) for palOA and palDTX1; and an Inertsil ODS column with methanol-0.2 M ammonium acetate (8:2, v/v) for YTX and YTXOH. Carboxylic acid toxins were selectively monitored on [M-H]- ions, sulfated toxins on [M-Na]-ions, and neutral toxins on [M+NH4]+ ions. Average recoveries of the toxins spiked to tissue homogenates ranged from 70 to 134%. Detection limits in the muscle ranged from 5 to 40 ng/g and those in the digestive glands from 10 to 80 ng/g. PMID- 11217025 TI - Determination of trace alkaline earth metals in brines using chelation ion chromatography with an iminodiacetic acid bonded silica column. AB - The chromatographic behaviour of alkaline earth metals on iminodiacetic acid bonded silica was studied. It was found that the ionic strength of the eluent greatly affected both retention time and selectivity by controlling the extent to which either simple ion exchange or surface complexation was responsible for retention. With a 0.1 M KNO3 eluent, the retention order was Mg(II), Sr(II), Ca(II) and Ba(II), indicating a strong contribution to retention from ion exchange. However, when using a 1.5 M KNO3 eluent, Ba(II) was found to elute first, indicating complexation to be more dominant under these conditions (pH 4.2). The effect of the ionic strength of the sample was also studied and it was found that by matching the eluent cation with that of the sample matrix, efficient separations of alkaline earth metals in 1.0 M NaCl and KCl brines could be obtained without matrix system peaks. Using post-column reaction with o cresolphthalein complexone, trace levels of Ca(II) and Mg(II) were determined in medicinal NaCl saline solution and laboratory-grade KCl. PMID- 11217026 TI - Influence of the carrier composition on thermal field-flow fractionation for the characterisation of sub-micron polystyrene latex particles. AB - A study on the influence of the carrier composition in a ThFFF system on the retention and thermal diffusion of sub-micron polystyrene latex particles has been carried out. Various factors that may influence retention were studied. These include: the type of electrolyte and surfactant, their respective concentrations, and the addition of an organic modifier. Particle retention is highly sensitive to small changes in the carrier composition. It is demonstrated that under the conditions applied, secondary effects, such as particle-wall and particle-particle interactions, are negligible. Addition of surfactants is required to minimise particle-wall interactions. Generally, retention increases at higher electrolyte concentration. Furthermore, the addition of acetonitrile (ACN) to an aqueous carrier leads also to an increased retention. The type of surfactant as well as its concentration is of influence on the retention time. The three surfactants that were studied, i.e., sodium dodecyl sulfate, Brij 35 and cetyltrimethylammonium bromide, showed significant differences in particle retention behaviour. The observed differences in retention in the carriers can be attributed to actual changes in thermal diffusion. D(T) appears to be mainly determined by the interaction between the particle's surface and the carrier liquid, and is therefore highly sensitive to changes in the chemical composition of the particle surface and the carrier. Strong differences in size selectivity were found for different carrier compositions. This allows a relatively easy optimisation of the separation. On the other hand, it complicates the size and composition analysis of particles. PMID- 11217027 TI - How to increase precision in capillary electrophoresis. AB - This review surveys approaches on how to improve precision in capillary zone electrophoresis and micellar electrokinetic chromatography. Many different techniques have been employed successfully to improve instrument precision and to facilitate method transfer between instruments and laboratories. Operational parameters as well as theories will be discussed in detail. PMID- 11217028 TI - Application of solvent microextraction to the analysis of nitroaromatic explosives in water samples. AB - The application of solvent microextraction to the analysis of nitroaromatic explosives is presented. Extraction of 11 nitroaromatics was achieved by suspending 1 microl of organic solvent to the tip of a microsyringe in a stirred aqueous solution. Parameters such as extraction solvent, stirring rate, salt concentration and sampling time were studied and optimized. The limits of detection using bench-top quadrupole mass spectrometry and short extraction times (15 min) were found to be between 0.08 and 1.3 microg/l and the relative standard deviations ranged between 4.3 and 9.8%. Although precision and accuracy of quantification of the method are still needed, solvent microextraction proved to be a fast, simple and inexpensive tool for preconcentration and matrix isolation of nitroaromatics on a microscale. PMID- 11217029 TI - Extraction of thiodiglycol from soil using pressurised liquid extraction. AB - Thiodiglycol (TDG) is the predominant hydrolysis product of the chemical warfare agent sulfur mustard. The extraction of TDG was investigated using pressurised liquid extraction and the results compared for a variety of different solvents and soils. TDG was analysed underivatised by gas chromatography with flame photometric detection. A mixture of methanol-water (9:1), proved to be the most efficient extracting solvent for TDG at a temperature of 150 degrees C and 10 MPa. PMID- 11217030 TI - Simple time weighted average level air-monitoring method for sulfur mustard in work places. AB - A simple air-monitoring method was developed and validated for vesicant sulfur mustard (HD) in the work place at time weighted average levels. XAD-2 adsorbent was used for the collection of HD vapours for 8 h followed by liquid desorption with carbon tetrachloride. The trace level analysis was carried out by gas chromatography-photoionization detection and was confirmed by gas chromatography mass spectrometric detection in the selected ion mode. PMID- 11217031 TI - Fast temperature programming in routine analysis of multiple pesticide residues in food matrices. AB - Flash gas chromatographic (GC) analysis of 15 organophosphorus pesticides commonly occurring in food crops was performed using the Thermedics Detection EZ Flash upgrade kit installed in the oven of a HP 5890 Series II Plus gas chromatograph. The temperature program and splitless time period were the main parameters to be optimized. In the first set of experiments wheat matrix-matched standards were analyzed both by: (i) the flash GC technique (resistive heating of a 5 m capillary column), and (ii) the conventional GC technique (moderate oven temperature programming of a 30 m capillary column). Using the flash GC technique, the analysis time was reduced by a factor of more than 10 compared to the conventional GC technique. Dramatically improved detectability of analytes was achieved due to much narrower peak widths. The flash GC technique was compared with another approach to faster GC analysis employing a 5 m column and fast temperature programming with a conventional GC oven. In comparison with this alternative, in the case of flash GC significantly better retention time repeatability was observed. The other superiority of resistive heating is very rapid cooling down (i.e., equilibration to the initial conditions) which contributes to the increased sample throughput. PMID- 11217032 TI - Supercritical fluid extraction and quantitative determination of organophosphorus pesticide residues in wheat and maize using gas chromatography with flame photometric and mass spectrometric detection. AB - An automated method using supercritical CO2 and clean-up by solid-phase extraction (SPE) using graphitized carbon black, has been developed for the quantitative determination of organophosphorus pesticide (OPP) residues in wheat and maize. Recoveries were as good as, or better than, those obtained using liquid extraction (LE) and gel permeation chromatography (GPC) for 10 OPP's spiked at levels equivalent to 0.05 and 0.50 microg/g. Lower limits of detection were possible using supercritical fluid extraction (SFE). Incurred residues were found in wheat and maize samples, and good agreement was obtained using SFE+SPE and LE+GPC. The SFE+SPE method required less analyst time and organic solvent, and hazardous waste was reduced. PMID- 11217033 TI - Solute-solvent interactions in micellar electrokinetic chromatography. Selectivity of lithium dodecyl sulfate-lithium perfluorooctanesulfonate mixed micellar buffers. AB - The solvation parameter model has been applied to the characterization of micellar electrokinetic chromatographic (MEKC) systems with mixtures of lithium dodecyl sulfate and lithium perfluorooctanesulfonate as surfactant. The variation in MEKC surfactant composition results in changes in the coefficients of the correlation equation, which in turns leads to information on solute-solvent and solute-micelle interactions. Lithium perfluorooctanesulfonate is more dipolar and hydrogen bond acidic but less polarizable and hydrogen bond basic than lithium dodecyl sulfate. Therefore mixtures of lithium dodecyl sulfate and lithium perfluorooctanesulfonate cover a very wide range of polarity and hydrogen bond properties, which in turn results in important selectivity changes for analytes with different solute properties. PMID- 11217034 TI - Optimisation of resolution in micellar electrokinetic chromatography by multivariate evaluation of electrolytes. AB - A novel approach to multivariate evaluation of separation electrolytes for micellar electrokinetic chromatography is presented. An initial screening of the experimental parameters is performed using a Plackett-Burman design. Significant parameters are further evaluated using full factorial designs. The total resolution of the separation is calculated and used as response. The proposed scheme has been applied to the optimisation of the separation of phenols and the chiral separation of (+)-1-(9-anthryl)-2-propyl chloroformate-derivatized amino acids. A total of eight experimental parameters were evaluated and optimal conditions found in less than 48 experiments. PMID- 11217035 TI - Fabrication of polyester microchannels and their applications to capillary electrophoresis. AB - Inexpensive and disposable polyester microchips were fabricated through photolithographic and wet-chemical etching procedure, followed by replication using an imprinting method at room temperature. Laboratory-scale laser-induced fluorescence equipment was employed as a detection system. The generation of electroosmotic flow (EOF) on the polyester channels was discussed in this paper. Surfactants in the running buffer had a significant effect on the EOF depending on their types. The epsilon potential of the electric double layer formed by adsorbing sodium lauryl sulfate molecules on the wall of polyester channels seemed to be constant within the buffer pH investigated. EOF could also be suppressed to zero by adding polyoxyethylene 23 lauryl ether into the running buffer. The separation of two laser dyes was obtained using polyester chips through both micellar electrokinetic chromatography and capillary zone electrophoresis. The polyester channels modified with 10-undecen-1-ol exhibited a dramatically high-separation efficiency compared with the conventional fused silica capillary tubes. PMID- 11217036 TI - Laser-induced fluorescence detection at 266 nm in capillary electrophoresis. Polycyclic aromatic hydrocarbon metabolites in biota. AB - The separation of five phenolic polycyclic aromatic hydrocarbon metabolites (hydroxy-PAHs) has been performed by cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC) using a 30 mM borate buffer (pH 9.0) containing 60 mM sodium dodecyl sulfate and varying concentrations of gamma cyclodextrin (gamma-CD). A concentration of 12.5 mM gamma-CD was found to provide a baseline separation of the five hydroxy-PAHs. We applied conventional fluorescence and laser-induced fluorescence (LIF) detection, using a new, small size, quadrupled Nd-YAG laser emitting at 266 nm. The best limits of detection, in the low ng/ml range, were achieved using LIF detection. For all analytes, linearity was observed up to ca. 100 ng/ml. As an application, conjugated pyrene metabolites in hepatopancreas samples from the terrestrial isopods Oniscus asellus and Porcellio scaber were separated and detected. Finally, flatfish bile samples from individuals exposed to polluted sediment or crude oil, which were part of an interlaboratory study, were analyzed by CD-MEKC with conventional fluorescence and LIF detection to determine the 1-hydroxypyrene concentrations. PMID- 11217037 TI - Determination of phenols in soil by supercritical fluid extraction-capillary electrochromatography. AB - A new analytical procedure is developed to couple supercritical fluid extraction with capillary electrochromatography (SFE-CEC) to extract and determine phenols in soil. Ten phenols consisting of phenol, methylphenols (p-cresol and o-cresol), dimethylphenols (3,5-xylenol, 3,4-xylenol and 2,6-xylenol), trimethylphenol, ethylphenols (p-ethylphenol and o-ethylphenol), and o-isopropylphenol are investigated. The use of supercritical CO2 with 10% methanol as the organic modifier was found to give satisfactory extraction of alkylphenols from soil at 1200 p.s.i. and 50 degrees C for 45 min under a total extractant flow-rate of 0.2 ml/min (1 p.s.i.=6894.76 Pa). Baseline resolution was achieved for the 10 selected phenols under optimised CEC conditions at 20 kV in a mobile phase of acetonitrile-4 mM Tris, pH 7.0 (35:65) in a 45 cm (25 cm packed with 3 microm ODS) x 75 microm I.D. fused-silica capillary column. Using SFE with a 10-fold preconcentration factor, all alkyl-substituted phenols in soil can be determined with detection limits ranging from 0.0032 to 0.014 mg/kg and working range from 0.019 to 2.72 mg/kg. The SFE-CEC procedure developed has been applied successfully to determine phenols extracted from real soil sample contaminated with medical disinfectant. It will provide a rapid method for the direct determination of phenol and alkyl-substituted phenol in soils, with capability for confirmation of unknown peaks. PMID- 11217038 TI - Trace analysis of gamma-cyclodextrin in a sample of beta-cyclodextrin by capillary electrophoresis. AB - A new capillary electrophoretic method for trace analysis of gamma-cyclodextrin, gamma-CD, in a sample of beta-CD has been developed, building on our recent work in which the tetraphenylborate ion, Ph4B-, was found to bind to gamma-CD three orders of magnitude more strongly than to beta-CD. The method involves measurement of the change of net electrophoretic mobility of Ph4B- and its CD complexes in a background electrolyte containing a fixed concentration of beta CD. Good linearity was found between 1/deltamu and 1/Cgamma where deltamu is the difference in the mobility of Ph4B- in the beta-CD solution at a given and at zero concentration of gamma-CD, and Cgamma the gamma-CD concentration. The limit of detection for gamma-CD in a beta-CD sample was found to be 0.020% (w/w), and high precision and accuracy were obtained. PMID- 11217039 TI - Development and validation of a capillary electrophoresis assay for the determination of 3,4-diaminopyridine and 4-aminopyridine including related substances. AB - A capillary electrophoresis (CE) assay has been developed for the quantitation and determination of the impurity profile of the potassium channel blockers 3,4 diaminopyridine and 4-aminopyridine. The compounds were separated from related substances using a capillary of 30 cm effective length, a 50 mM phosphate buffer, pH 2.5 and an applied voltage of 25 kV. The assay was validated with respect to specificity, linearity, range, limits of quantitation and detection, precision and robustness. The method allows the detection and quantitation of impurities at the 0.05% level. The feasibility of the assay was demonstrated by analyzing a commercial sample of 3,4-diaminopyridine. All known related substances could be detected in this sample with the present CE method. PMID- 11217040 TI - Sulfur speciation and tetrathionate sulfitolysis monitoring by capillary electrophoresis. AB - Capillary electrophoresis (CE) with indirect detection was used to analyse mixtures of sulfur-containing compounds. An optimised electrolyte, composed of 2 mM sulfosalicylic acid-0.5 mM Waters osmotic flow modifier OFM-OH, pH adjusted to 7.00 with Bis-Tris, allowed the analysis of sulfide (H2S/HS-), thiosulfate (S2O(3)2-), tetrathionate (S4O(6)2-), trithionate (S3O(6)2-), sulfite (HSO3 /SO(3)2-), sulfate (SO(4)2-), and peroxodisulfate (S2O(8)2-). Only sulfate showed a single-peak electropherogram that gives evidence of its stability in aqueous solutions. Thiosulfate, tetrathionate and peroxodisulfate showed an additional minor peak of sulfate that did not seem to be time-dependent and was supposed to be due to salt impurities. Sulfide and sulfite showed rapid conversion into their oxidation products in solutions exposed to air. Linear calibration curves were obtained for all these species, taking the oxidation process into account for sulfide and sulfite. Limits of detection were in the low- to mid-microM range, except for sulfide, for which the limit of detection was 10(-5) M. The identity of trithionate was not determined via standard solutions (not commercially available) but after the rearrangement of tetrathionate with sulfite that yields thiosulfate and trithionate. The time-dependence of the concentrations of both the reagents and products could be followed simultaneously by the proposed CE method and the reaction kinetics were found to be second order in the pH range 7 to 11. A calibration curve for trithionate could be deduced from this study. PMID- 11217041 TI - Effect of liquid chromatography separation of complex matrices on liquid chromatography-tandem mass spectrometry signal suppression. AB - The effect of liquid chromatography separation on liquid chromatography-tandem mass spectrometry (LC-MS-MS) signal response for the characterization of low molecular-mass compounds in a complex matrix was investigated. Matrix induced signal suppression appears throughout the entire LC-MS-MS analysis of wheat forage extract, with greatest suppression occurring at early retention times. Experimental results show that co-elution of matrix components and analytes from the LC column may be most strongly attributed to column overloading rather than similar analyte and matrix retention behavior. As a result, two-dimensional (LC LC) separation can be a highly effective approach to address signal suppression effects for the quantitative LC-MS-MS analysis of complex matrix samples. PMID- 11217042 TI - High-speed counter-current chromatography separation and purification of resveratrol and piceid from Polygonum cuspidatum. AB - High-speed counter-current chromatography (HSCCC) was applied to the separation and purification of resveratrol and piceid from the dried roots (20.0 g) of Polygonum cuspidatium. The EtOAc extracts were separated with chloroform-methanol water (4:3:2, v/v). Resveratrol was identified in fraction 5. The water extracts were separated first with EtOAc-EtOH-water (10:1:10, v/v) and then with the same solvent system at the modified volume ratio of 70:1:70. Yields of resveratrol and piceid obtained were 2.18% and 1.07%. Chemical structures of the purified resveratrol and piceid were confirmed by electrospray ionization MS and 1H nuclear magnetic resonance spectroscopy. PMID- 11217043 TI - Corrections to moving chemical reaction boundary equation for weak reactive electrolytes under the existence of background electrolyte KCl in large concentrations. AB - In this report, the moving chemical reaction boundary (MCRB) was formed by the weak reaction electrolytes of NH3.H2O and CH3COOH under the existence of background electrolyte KCl in large concentrations, the experiments were compared with the predictions by the moving chemical reaction boundary equation (MCRBE) for weak reactive electrolytes. It was found that the experimental results are far from the predictions with the MCRBE. So the MCRBEs must be corrected under the given experimental conditions. The corrected MCRBEs are given for the MCRB formed with weak reactive electrolytes coupled with KCl at high concentrations. PMID- 11217044 TI - Recalculation of the temperature inside capillaries using high buffer concentrations. PMID- 11217045 TI - Joule heating calculations in capillary zone electrophoresis. Reply to "Recalculation of the temperature inside capillaries using high buffer concentrations" by Zhang et al. PMID- 11217046 TI - 4-(6,7-Dihydro-5,8-dioxothiazolo[4,5-g]phthalazin-2-yl)benzoic acid N hydroxysuccinimide ester as a highly sensitive chemiluminescence derivatization reagent for amines in liquid chromatography. AB - 4-(6,7-Dihydro-5,8-dioxothiazolo[4,5-g]phthalazin-2-yl)benzoic acid N hydroxysuccinimide ester was synthesized as a highly sensitive and selective chemiluminescence derivatization reagent for primary and secondary amines in liquid chromatography. Methyl-n-octylamine, n-nonylamine and n-decylamine were used as model compounds to optimize the derivatization, separation and chemiluminescence reaction conditions. This reagent reacts selectively with amines in the presence of triethylamine to give the highly chemiluminescent derivatives, which produce chemiluminescence by reaction with hydrogen peroxide in the presence of potassium hexacyanoferrate(III) in an alkaline medium. The chemiluminescent derivatives of the three amines can be separated within 20 min by reversed-phase liquid chromatography with isocratic elution, followed by chemiluminescence detection. The detection limits (signal-to-noise ratio=3) for primary and secondary amines are at sub-fmol levels for a 20-microl injection. Furthermore, this method was applicable to the determination of amantadine in human plasma. PMID- 11217047 TI - Chiral beta-cyclodextrin-based polymer supports prepared via ring-opening metathesis graft-polymerization. AB - A series of norborn-2-ene-derivatized beta-cyclodextrins (beta-CDs), 6-O-(norborn 2-ene-5-carboxyl)-beta-CD (1), tetrakis(6-O-norborn-2-ene-5-carboxyl)-beta-CD (2), (3), 6-O-(6-norborn-2-ene-5-car-6-O-(7-oxanorborn-2-ene-5-carboxyl)-beta-CD bonylaminohexoyl)-beta-CD (4), 6-O-(norborn-2-ene-5-ylmethoxymethylsilyl)-beta-CD (5), tris(6-O-norborn-2-ene-5-ylmethoxymethylsilyl)-beta-CD (6), tetrakis(6-O norborn-2-ene-5-ylmethoxymethylsilyl)-beta-CD (7) and hexakis(6-O-norborn-2-ene-5 ylmethoxymethylsilyl)-beta-CD (8), have been synthesized. Compounds 1-3 were prepared via reaction of beta-CD with norborn-2-ene-5-carboxylic chloride and 7 oxanorborn-2-ene-5-carboxylic chloride, respectively; compounds 5-8 were synthesized from norborn-2-ene-5-yl-methyldichlorosilane and beta-CD, respectively. Compound 4 was accessible by reaction of norbom-2-ene-5 carboxylaminohexoyl chloride with beta-CD. Compounds 1-8 were surface grafted onto norborn-2-ene-derivatized silica-based supports using ring-opening metathesis polymerization employing the ruthenium-based initiator bis(tricyclohexylphosphino)benzylideneruthenium dichloride [Cl2Ru(CHC6H5)(PCy3)2, Cy=cyclohexyl, 9]. Generally speaking, the resulting chiral stationary phases (CSPs) I-VIII may be prepared with high reproducibility and may be used within a pH of 2-10. Thus, relative standard deviations (sigman-1) of the mean resolution (Rs) are <7%. The CSPs were used for the enantioselective separation of beta blockers, N-dansyl-, N-3,5-dinitrobenzoyl- and Fmoc-protected amino acids and were characterized in terms of chemical stability, selectivity (alpha') and resolution (Rs). Additionally, the role of the spacer as well as influences of capacity and the degree of substitution of the beta-CD moiety on the separation characteristics were determined. PMID- 11217048 TI - Determination of the pore connectivity and pore size distribution and pore spatial distribution of porous chromatographic particles from nitrogen sorption measurements and pore network modelling theory. AB - The pore connectivity, pore size distribution and pore spatial distribution of the porous structure of native and silanized silica particles were determined by matching the experimental nitrogen sorption data with the theoretical results obtained from pore network model simulations. The agreement between theory and experiment is found to be good. The results clearly indicate that the deposition of the silane layer to the pore surfaces of the native silica particles produces a silanized silica particle with a mean pore diameter and pore connectivity smaller than that of the native silica particle. Furthermore, the evaluation of the pore diffusivity of ribonuclease under unretained conditions shows that the lower values of the pore connectivity found in the samples of silanized silica particles, when compared with the values of the pore connectivity obtained for the native silica particles, increase the diffusional mass transfer resistance within the porous structure of the silanized silica particles. PMID- 11217049 TI - Influences of surface chemistry on the separation behavior of stationary phases for reversed-phase and ion-exchange chromatography: a comparison of coated and grafted supports prepared by ring-opening metathesis polymerization. AB - A series of poly(norborn-2-ene) (poly-NBE), poly(7-oxanorborne-2-ene-5,6 dicarboxylic acid) (poly-ONDCA), as well as poly(norborn-2-ene-co-7-oxanorborne-2 ene-5,6-dicarboxylic acid) (poly-NBE-co-ONDCA) based silica supports were prepared via ring-opening metathesis polymerization (ROMP) using both coating and grafting techniques. Poly-NBE-grafted and poly-NBE-coated supports were used for the reversed-phase separation of phenols; poly-NBE, poly-ONDCA as well as poly NBE-co-ONDCA-grafted supports were used for comparative studies on the separation of a series of anilines and lutidines. As expected, grafted supports possess superior separation capabilities compared to their coated analogues. Compared to pure poly-NBE- and poly-ONDCA-grafted stationary phases, supports consisting of poly-NBE-co-ONDCA block-copolymers possess both hydrophobic and ion-exchange sites and represent optimum stationary phases for the separation of isomeric basic analytes. PMID- 11217050 TI - Bi-quadratic surface response for quantitative determination of analytes leading to partially overlapped chromatographic peaks. AB - A simple analytic approach is described for the accurate determination of the concentration of components which give rise to partially overlapped chromatographic peaks. This method requires neither deconvolution processes nor chromatographic separation of the peaks. From the empirical point of view a bi quadratic function has been found relating the area of an unresolved peak with the concentrations of the related analyte and of the interfering one. Such concentrations are then computed by solving the related non linear system of equations by the Newton-Raphson method. PMID- 11217051 TI - Molecularly imprinted polymer membranes for substance-selective solid-phase extraction from water by surface photo-grafting polymerization. AB - Hydrophilized polyvinylidene fluoride microfiltration membranes were surface modified in the presence of a template (terbumeton) in methanol with a graft copolymer of a functional monomer (2-acrylamido-2-methyl-1-propane sulfonic acid, AMPS, methacrylic acid, MAA, or acrylic acid, AA) and a cross-linker (N,N' methylene-bis-acrylamide) using UV irradiation and benzophenone as photoinitiator. As result, membranes covered with a thin layer of imprinted polymer selective to terbumeton were obtained. Blank membranes were prepared with the same monomer composition, but in the absence of the template. The membranes' capacity to adsorb terbumetone from aqueous solution was evaluated yielding information regarding the effect of polymer synthesis (type and concentration of functional monomer, concentration of cross-linker) on the resulting membranes' recognition properties. UV spectroscopic studies of the interactions with terbumetone revealed that AMPS forms a stronger complex than MAA and AA. In agreement with that finding, imprinting with AMPS gave higher affinities than with MAA and AA. The terbumeton-imprinted membranes showed significantly higher sorption capability to this herbicide than to similar compounds (atrazine, desmetryn, metribuzine). With the novel surface modification technology, the low non-specific binding properties of the hydrophilized microfiltration membrane could successfully be combined with the receptor properties of molecular imprints, yielding substance-specific molecularly imprinted polymer composite membranes. The high affinity of these synthetic affinity membranes to triazine herbicides together with their straightforward and inexpensive preparation provides a good basis for the development of applications of imprinted polymers in separation processes such as solid-phase extraction. PMID- 11217053 TI - A case of canine primitive neuroectodermal tumor (PNET). AB - A 2-year and 6 month-old, female, Golden Retriever showed circling behavior and seizure. By magnetic resonance imaging (MRI) examination, a mass was found on the surface of the left cerebral hemisphere, invading to the left temporal muscle. The skull bone between them was destroyed. The dog was euthanized and necropsied. Histologically, the mass contained a lot of undifferentiated anaplastic cells, forming Homer-Wright rosettes and pseudopalisading patterns. Thus, the case was diagnosed as primitive neuroectodermal tumor (PNET). PMID- 11217052 TI - Immunohistochemical analysis of cytokeratin expression in dog skin. AB - The expression of cytokeratins and involucrin was analyzed to identify the skin cells which compose the epidermis of dogs. The distribution of cytokeratins and involucrin in normal dog skin was immunohistochemically examined with 27 commercial monoclonal antibodies for human use. Antibodies, No.4. OV-TL12/13, 35betaH11, 4.1.18, CAM5.2, NCL5D3, Ks.13.1, Ks.18.04, Ks.19.1, 170.2.]4 and Ks.20.8 stained hair follicles and/or the sweat gland duct, but not the epidermis. Antibodies, 34betaB4, AE3, 34betaE12. LP34, RCK102, MNF116, AE1, KLI, DE-K10 and DE-K13 reacted with every layer of the epidermis, hair follicles and the sweat gland duct. These results were similar to those reported in the human skin. No positive staining, however, could be detected in the epidermis, hair follicles and the sweat gland duct with commercial antibodies, 6B10, Ks.7.18, Mu146-uc, E3, RCK108 and involucrin. Therefore, immunohistochemical investigation with these commercial antibodies developed for human skin examination might be available for investigating the origin of skin tumors in dogs. PMID- 11217054 TI - Pleomorphic rhabdomyosarcoma in a cow. AB - In a 5-year-old Holstein cow, a neoplasm composed of a large intramuscular mass and multiple metastases in the lungs and lymph nodes was diagnosed as a pleomorphic rhabdomyosarcoma. This neoplasm was characterized by marked variation in tumor cell size and giant cells with single bizarre nuclei. Although the presence of cross striations and myoglobin could be confirmed, expression of alpha-smooth muscle actin (SMA) was also recognized in a few cells. Neoplastic cells showing intense staining for desmin, vimentin and proliferating cell nuclear antigen irrespective of their size differed from those in an embryonal rhabdomyosarcoma that exhibited a wide spectrum of differentiation, reminiscent of normal skeletal myogenesis. The cellular pleomorphism and SMA expression seemed to be characteristic of deviation from normal muscle cells or satellite cells in adult muscle. PMID- 11217055 TI - Immunolocalization of gastrin-releasing peptide in the bovine uterus and placenta. AB - Gastrin-releasing peptide (GRP), a mammalian homologue of amphibian bombesin, has been suggested to be a novel regulatory peptide in the reproductive tract during pregnancy. In this study, the localization of GRP in the bovine uterus and placenta was demonstrated by immunohistochemistry. Uterine and placental samples were collected from nonpregnant and pregnant specimens, respectively. Tissue sampling was done from the caruncle and intercaruncle of the uterus, and from the placentome (caruncle and cotyledon) and intercotyledon of the placenta. In all the tissues examined, GRP was detected although its immunoreactivity was observed at various degrees. In the uterus, moderate immunoreactivity for GRP was observed in the uterine gland epithelial cells. In the placenta, strong immunoreactivity for GRP was demonstrated in the uterine gland epithelial cells; moderate in superficial epithelial cells; and weak in the trophoblasts, trophoblastic giant cells and cryptal epithelial hybrid cells. In both nonpregnant and pregnant animals, GRP was immunolocalized in the uterine gland secretions and was found predominantly in the supranuclear region of the uterine gland epithelial cells. These findings may suggest that GRP is secreted into the uterine lumen and regulates the intrauterine environment of both the nonpregnant and pregnant bovine by exocrine, autocrine and/or paracrine manner. PMID- 11217056 TI - Detection of babesia species from infected dog blood by polymerase chain reaction. AB - Polymerase chain reaction (PCR) was first applied to diagnosis of canine babesiosis in Japan. Blood samples from 13 dogs suffering from canine babesiosis were used for examination of specificity and sensitivity of the PCR diagnosis. Of the 13 dogs, three were experimentally infected, and ten were naturally infected with Babesia species in west part of Japan. We designed a nested PCR to amplify the babesial small subunit ribosomal RNA gene and found that only the nested PCR produced a visual band, which were not apparent by the first-round PCR to the positive samples. Specificity of the nested PCR was confirmed by amplification after the second-round PCR. Sensitivity of the nested PCR was examined by diluting the blood samples from infected and uninfected dogs. The nested PCR was found to show positive results on the most diluted blood at 0.0001% parasitemia. These results indicate that the nested PCR is highly sensitive and useful for diagnosis of canine babesiosis. PMID- 11217057 TI - Differentiation of stromal-vascular cells isolated from canine adipose tissues in primary culture. AB - A culture condition supporting adipocyte differentiation of stromal-vascular (S V) cells isolated from canine adipose tissues was established. Morphological observation and determination of glycerol-3-phosphate dehydrogenase (GPDH) activity were used as the criteria for adipocyte differentiation. After reaching confluence, the cells were able to undergo terminal adipocyte differentiation by treatment with 100 microM indomethacin, 10 microg/ml insulin and 0.5 mM 1-methyl 3-isobutylxanthine (MIX) in medium supplemented with 5% fetal calf serum (FCS). In the absence of either indomethacin or insulin, the S-V cells did not undergo adipose conversion and GPDH activity was not increased, indicating that both indomethacin and insulin play essential roles in this culture system. The S-V cells from inguinal adipose tissues exhibited the greatest increase in GPDH activity among the four depots (inguinal > abdominal-subcutaneous > perirenal > omental). demonstrating that adipocyte differentiation was also intensely dependent on anatomic sites from which the S-V cells were derived. Interestingly, dimethylsulfoxide (DMSO) was found to accelerate adipocyte differentiation in combination with indomethacin and insulin. Under this condition, up to 90% of the cells displayed adipocyte phenotypes and the GPDH activity reached 1288 +/- 441 mU/mg protein. This culture system may be useful for investigating other adipogenic factors as well as anti-adipogenic factors involved in the regulation of canine adipose tissue development. PMID- 11217058 TI - Effects of short photoperiod on the expression of smad2 and smad3 mRNA in Syrian hamster testis. AB - The testicular localization and expression of Smad2 and Smad3 mRNA involved in the intracellular signal transduction of activin, inhibin and transforming growth factor-beta (TGF-beta) were examined under the influence of long and short photoperiod in Syrian hamsters (Mesocricetus auratus). In situ hybridization detected both Smad2 and Smad3 mRNA in spermatogonia and premeiotic spermatocytes in the active testis exposed to a long photoperiod, as well as in the regressed testis exposed to a short photoperiod. Northern blots showed that Smad2 mRNA was expressed at all stages over long and short photoperiods, whereas Smad3 mRNA was expressed at high levels in the photoperiod-induced regressed testis. The photoperiodic condition would change the balance between Smad2 and Smad3 transcripts in the testis. Thus, intracellular Smad2 and Smad3 might participate in transducing signals from activin, inhibin and TGF-beta in spermatogenetic cells. PMID- 11217059 TI - The cycle of the seminiferous epithelium in the greater Japanese shrew mole, Urotrichus talpoides. AB - Spermatogenesis and acrosomal formation in the greater Japanese shrew mole, Urotrichus talpoides, were studied by light microscopy. On the basis of acrosomal changes, morphology of spermatid head, nuclear shape, appearance of meiotic figures, location of spermatid and period of spermiation, the cycle of the seminiferous epithelium was classified into 12 stages, and developing spermatids could be divided into 15 steps. The mean relative frequencies of stages from I to XII were 10.9, 8.7, 9.8, 7.3, 8.5, 10.3, 12.5, 8.7, 5.8, 5.4, 5.1 and 7.1%, respectively. Similar to the case in the musk shrew, the spermatid nucleus of the greater Japanese shrew mole remained in the middle region of the seminiferous epithelium and only the acrosome extended towards the basement membrane. The elongation of the acrosome, however, was not prominent. The proacrosomal vesicle first appeared in stage II and then one large and round granule was seen in stage III. The acrosomal vesicle became flattened on the surface of the nucleus in stage IV. Spreading of the acrosomic system has been recognized from stage VII. In stage VII, spermiation occurred. In stage IX, the spermatid nucleus began to elongate. Elongation and condensation of the nucleus were clearly observed in stage X. In stage XII, pachytene spermatocytes divided into diplotene spermatocytes. In stage XII, meiotic figures and secondary spermatocytes were observed. PMID- 11217060 TI - Mechanisms of NO-resistant relaxation induced by acetylcholine in rabbit renal arteries. AB - The effects of K+ channel blockers and P2Y receptor agonist/antagonist on the vasorelaxation mediated by endothelium-derived hyperpolarizing factor (EDHF) were investigated in the rabbit renal artery. Acetylcholine (ACh, 1 nM-10 microM) induced endothelium-dependent relaxation of arterial rings precontracted with norepinephrine (NE, 1 microM) in a concentration-dependent manner. NG-nitro-L arginine (L-NAME. 0.1 mM), an inhibitor of NO synthase, partially inhibited the ACh-induced endothelium-dependent relaxation. The ACh-induced relaxation was only partially inhibited by L-NAME whereas combined addition of L-NAME and 30 mM KCl completely inhibited the relaxation. The ACh-induced relaxation observed in the presence of L-NAME was significantly reduced by a combination of iberiotoxin (0.1 microM) and apamin (1 microM), and almost completely blocked by 4-aminopyridine (5 mM). The ACh-induced relaxation was antagonized by P2Y receptor antagonist, cibacron blue (10 and 100 microM) in a concentration-dependent manner. Furthermore, ADPbetaS, a potent P2Y agonist, induced the endothelium-dependent relaxation, and this relaxation was markedly reduced by either the combination of iberiotoxin and apamin or by cibacron blue alone. In conclusion, ACh may activate the release of ATP from endothelial cells which in turn activates a P2Y receptor on the endothelial cells followed by a release of EDHF, resulting in a vasorelaxation via a mechanism that involves activation of both the voltage-gated K+ channels and the Ca2+-activated K+ channels. EY WORDS: ATP, K+ channel, rabbit renal artery. PMID- 11217061 TI - Mechanisms of acetylcholine-induced vasorelaxation in high K+-stimulated rabbit renal arteries. AB - To characterize the mechanisms of acetylcholine (ACh)-induced vasorelaxation in rabbit renal arteries precontracted with high K+ (100 mM), muscle tension and cytosolic free Ca2+ concentration ([Ca2+]i) were measured simultaneously in the fura-2-loaded arterial strips. In the artery with endothelium, high K+ increased both [Ca2+]i and muscle tension. Addition of ACh (10 microM) during high-K+ induced contraction significantly relaxed the muscle and induced additional increase in [Ca2+]i. In the presence of NG-nitro-L-arginine (L-NAME, 0.1 mM). ACh increased [Ca2+]i without relaxing the muscle. In the artery without endothelium, high K+ increased both [Ca2+]i and muscle tension although ACh was ineffective, suggesting that ACh acts selectively on endothelium to increase [Ca2+]i. 4-DAMP (10 nM) or atropine (0.1 microM) abolished the ACh-induced increase in [Ca2+]i and relaxation. However, pirenzepine (0.1 microM), AF-DX 116 (1 microM) and tropicamide (1 microM) were ineffective. The ACh-induced increase of [Ca2+li and vasorelaxation was significantly reduced by 3 microM gadolinium, 10 microM lanthanum or 10 microM SKF 96365. These results suggest that, in rabbit renal artery, ACh-evoked relaxation of 100 mM K+-induced contractions is mediated by the release of endothelial NO. ACh may stimulates the M3 subtype of muscarinic receptor in the endothelial cells, resulting in the opening of the nonselective cation channels followed by an increase of [Ca2+]i and stimulation of NO synthase. PMID- 11217062 TI - Dynamic changes in plasma concentrations of gonadotropins, inhibin, estradiol 17beta and progesterone in cows with ultrasound-guided follicular aspiration. AB - To elucidate the effects of ultrasound-guided transvaginal follicular aspiration, plasma concentrations of FSH, LH, inhibin, estradiol-17beta and progesterone, and folliculogenesis were examined in Holstein cows. Four clinically healthy cows with regular estrous cycles were scanned by ultrasound per rectum once a week for 9 weeks before the commencement of follicular aspiration. All visible follicles were divided into 3 categories based on their sizes (2 < or = small < 5 mm; 5 < or = medium < 10 mm, large > or = 10 mm). The follicular aspiration was started at random during the estrous cycle and conducted under epidural anesthesia induced with 5 ml of 2% lidocaine once a week for 6 weeks. The average number of total visible follicles > or = 2 mm in diameter at 7 days after aspiration (21.7 +/- 7.4, n = 24) was similar to that before starting aspiration (26.7 +/- 10.5, n = 36). Plasma inhibin and estradiol-17beta declined and fell to a trough on 1.5 days and returned to pre-aspiration values by 5 days after aspiration. Plasma concentrations of FSH increased and reached peak levels between 1 and 1.5 days after aspirations. Plasma concentrations of LH also increased and reached peak levels between 0.5 and 1.5 days after aspirations. Both plasma FSH and LH had returned to pre-aspiration levels by 5 days after aspirations. Plasma concentrations of progesterone did not change with the follicular aspiration. These results demonstrate that follicular aspiration decreases plasma concentrations of inhibin and estradiol-17beta, which in turn leads to a rise in plasma concentrations of FSH and LH. It is suggested that marked increases in plasma concentrations of FSH and LH after the aspiration stimulate the development and maturation of a new cohort of follicles within one week in cows. PMID- 11217063 TI - Effects of exposure of lactating female rats to polychlorinated biphenyls (Pcbs) on testis weight, sperm production and sertoli cell numbers in the adult male offspring. AB - To investigate the effects of intermittent and continuous exposure of lactating rats to Aroclor 1242 (a PCB congener), testis weight, daily sperm production (DSP) and Sertoli cell number per testis were examined in the adult male offspring. Thyroxine (T4) was also measured because of the well-documented effects of polychlorinated biphenyls (PCBs) on this hormone. In experiment 1.3 groups of lactating female rats received daily subcutaneous injections of low (0.8 mg) or high (1.6 mg) doses of Aroclor 1242 in 0.1 ml corn oil from parturition to weaning of pups at 21 days. In experiment II, 3 groups of lactating rats received 2 subcutaneous injections per week of 0.8 or 1.6 mg Aroclor 1242, as in experiment 1. In both experiments, control rats received vehicle alone. Serum T4 was measured at 21 and 90 days of age, and testis weight, DSP and Sertoli cell numbers were examined at 90 days. In experiment I (continuous exposure), both the low (0.8 mg) and high (1.6 mg) doses suppressed T4 concentrations at 21 days of age. Testis weight was increased by 14.8% (LD) and 16.5% (HD) compared with controls. DSP was increased by 20.4% in the low dose and 25% in the high dose animals compared with controls. The number of Sertoli cells per testis was increased by 32.6 and 39.4% in low and high dose animals, respectively. A similar study in which the lactating females were only dosed twice per week (experiment 11) did not show any differences in these parameters. These results indicate that continuous exposure of lactating female rats to PCBs increases testis weight, sperm production and Sertoli cell numbers in the adult male offspring. PMID- 11217064 TI - Application of short-time magnetic resonance examination for intervertebral disc diseases in dogs. AB - The usefulness of magnetic resonance (MR) is already established, but it has a disadvantage of requiring a long scanning time. A short-time examination is more or less needed so as to be more practical in veterinary clinics. A protocol of the short-time MR examination was devised based on parameters determined, and validity of the protocol was assessed through the diagnosis of clinical cases with intervertebral disc diseases. With this protocol, it was possible to complete an MR examination for the spine within 15 min. The MR images and myelographic findings were correlated well in this study, suggesting the short time protocol of MR examination can be used in the clinical diagnosis of spinal diseases. PMID- 11217065 TI - Distribution of reticulocerebellar neurons in chicken reticular formation. AB - The distribution of reticulocerebellar (RC) neurons was examined by the retrograde transport of horseradish peroxidase (HRP) or wheat germ agglutinin bound to HRP (WGA-HRP) in 7 White Leghorn chickens. A large number of labeled cells were found in the nucleus reticularis pontis caudalis (RP) of the pontomedullary junction and in the nucleus reticularis gigantocellularis (Rgc), parvocellularis (Rpc), subtrigiminalis (Rst), paragigantocellularis (Rpg) and paramedianus (RpaM) in the medulla. Slightly ventral to the vestibulocochlear nerve were many large RC neurons arranged in a longitudinal manner along the lateral edge of the brainstem reticular formation (the Dorsolateral edge cells, DLe cells). RC neurons were most numerous in the Rgc and accounted for 31.9% of the total number of labeled cells, followed by RP (24.2%), Rpc (12.7%), Rpg (10.8%), RpaM (6.7%), DLe cells (6.3%) and Rst (4.9%). The great number of RC neurons was found around the levels of the vestibulocochlear nerve. PMID- 11217066 TI - Analysis by enzyme-linked immunosorbent assay and 2-dimensional electrophoresis of haptoglobin in the high-density lipoprotein fraction in cows. AB - Haptoglobin (Hp) is a hemoglobin (Hb)-binding acute-phase protein. Besides its relevance in inflammation, Hp is involved in the regulation of lipid metabolism. In cattle, in addition to the lipoprotein-deficient fraction, Hp is distributed in high-density lipoprotein (HDL) and very high-density lipoprotein (VHDL) fractions. The purpose of this study was to determine Hp concentrations in the lipoprotein fractions using an enzyme-linked immunosorbent assay (ELISA) based on the affinity with Hb, and also to detect structural differences of HDL Hp from that in the lipoprotein-deficient fraction using 2-dimensional electrophoresis. When purified Hp was used as the antigen for the ELISA, the detection limit was 7.4 ng/ml and linearity was obtained from 14.8 to 475 ng/ml. The correlation coefficient between the ELISA and single radial immunodiffusion was 0.884. The ELISA was shown to be applicable to evaluate Hp concentrations in the lipoprotein fractions. Hp concentrations in the lipoprotein fractions were in the range of 0.94 to 8.77 microg of Hp/ml (n = 4), and concentration ratios were 0.2 to 0.3% of whole serum Hp. Of the lipoprotein fractions, Hp was most abundant in HDL, moderate in VHDL and faint in chylomicrons, the very low-density lipoprotein fraction and low-density lipoprotein fraction. By 2-dimensional electrophoresis, alpha- and beta-chains of serum Hp were each separated into 5 spots, and their isoelectric point (pI) values were from 5.05 to 6.28 in the alpha-chain and from 5.92 to 6.95 in the beta-chain. The pI values of HDL Hp were indistinguishable from those of serum Hp. These results indicate that the ELISA based on the affinity with Hb is useful for evaluating Hp concentrations in lipoprotein fractions, and also suggest that HDL Hp is structurally similar to that in the lipoprotein-deficient fraction. PMID- 11217067 TI - Effect of enrofloxacin-Na against pathogens related to the respiratory and alimentary diseases in suckling and weanling piglets. AB - A field trial was conducted to evaluate effect of enrofloxacin-Na against pathogens related to the respiratory and alimentary diseases in eighty suckling piglets (6-7 days old) and eighty weanling piglets (5-6 weeks old). Respective twenty of the suckling and weanling piglets were assigned to each of 4 experimental groups; control (non-treated), clinical injection dose (CID), 2x clinical injection dose (2CID). and premix. A 0.05 ml (2.5 mg) of enrofloxacin-Na injection (5% solution, 1 ml) per kg body weight of piglets as CID was injected intramuscularly for 3 days and the clinical signs were observed for 9 days. The premix (150 ppm) of enrofloxacin-Na was administered with feed for 7 days ad libitum and the clinical signs were observed for 13 days. The enrofloxacin-Na treated piglets showed a higher increase in body weight and a lower feed per gain than the control piglets. In addition, the treatment of enrofloxacin-Na, regardless of the route of administration, decreased the incidence rate of diarrhea in suckling piglets and respiratory symptoms in weanling piglets. The isolation index of E. coli and Cl. perfringens during the treatment periods was also lowered by the enrofloxacin-Na treatment in both suckling and weanling piglets. The antibiotics was also evaluated as safe locally and whole bodily as treated by injection or feeding. These results indicate that the newly developed antibiotics, enrofloxacin-Na, is very useful for the prevention and therapy of swine diseases in the pig industry. PMID- 11217068 TI - The complete nucleotide sequences of L3 and S7 segments of Ibaraki virus encoding for the major inner capsid proteins, VP3 and VP7. AB - The complete nucleotide sequences of the genes encoding two of the major inner capsid proteins of Ibaraki virus (IBAV), belonging to epizootic hemorrhagic disease virus serotype 2 (EHDV-2) were determined. The L3 RNA segment is 2768 nucleotides in length which encodes VP3 polypeptides of 899 amino acid residues (M.W. 103 kDa). The S7 RNA segment, which encodes the VP7 core protein, is 1162 nucleotides in length and encodes 349 amino acids (M.W. 38 kDa). These RNA segments had the characteristic consensus motifs of Orbivirus RNA segments in termini, namely 5'-GUUAAA... and ...ACUUAC-3'. The comparison of the IBAV L3 and S7 sequences with those of other two EHDV-2 isolates revealed the higher homologies of 93% and 92% against EHDV-2 Australia isolate (EHDV-2AUS) and lower homologies of 80% and 81% against EHDV-2 North America isolate, respectively. The phylogenetic analysis based on L3 and S7 genes also indicated close relationships between IBAV and EHDV-2AUS. PMID- 11217069 TI - Seasonal rhinitis in a cat sensitized to Japanese cedar (Cryptomeria japonica) pollen. AB - A cat showing seasonal allergic symptoms of rhinitis was examined for reactivities to Japanese cedar (Cryptomeria japonica, CJ) pollen allergen by intradermal skin test (IDST), Prausnitz-Kustner (P-K) test, and lymphocyte blastogenic response. In IDST for 26 common allergens. the cat showed a positive reaction to CJ pollen allergen. P-K test using CJ pollen allergen also showed a positive reaction, indicating the presence of serum IgE specific to CJ pollen. In the lymphocyte blastogenic response, the stimulation index in the presence of CJ pollen allergen was 2.4. These data suggested that the seasonal rhinitis observed in the cat was caused by the sensitization to CJ pollen allergen. PMID- 11217070 TI - Effect of retinoids on growth inhibition of two canine melanoma cell lines. AB - Two new canine melanoma cell lines (CMM1 and CMM2) were established from the patients with oral malignant melanomas. Histopathological type of both CMM1 and CMM2 was a mixed cell type consisted of spindle-shaped cells, polygonal cells, and oval cells. Doubling time of CMMI and CMM2 were 18.4 +/- 1.96 hr and 21.0 +/- 0.73 hr, respectively. The effect of two kinds of retinoids (all-trans retinoic acid and 9-cis retinoic acid) on the proliferation of these cells were examined by morphological changes, proliferation assay and apoptosis assay. However, the retinoids did not suppress growth rate of these cells. This result suggests that retinoids used in this study did not induce differentiation, apoptosis, and growth inhibition of the canine melanoma cell lines. PMID- 11217072 TI - Esophageal adenosquamous carcinoma in a cat. AB - Esophageal carcinoma was observed in an eight-year-old, castrated male, Japanese domestic cat. Histologically, this neoplasm consisted of two different growth patterns, squamous cell carcinoma and adenocarcinoma. The results of immunohistochemical examination supported the fact that the two kinds of neoplastic cells have different characteristics. The tumor was, therefore, diagnosed as adenosquamous carcinoma. Esophageal tumors in the cat are very rare and, if any, neither adenocarcinoma nor adenosquamous carcinoma has been reported up to the present. PMID- 11217071 TI - A case of pulmonary acariasis in lung of Japanese macaque. AB - A 20-year-old female Japanese macaque, weighing 8.7 kg, developed severe pulmonary acariasis. Numerous whitish nodules, 2-4 mm, were scattered throughout the lungs. Histologically multifocal granulomatous lesions consisting of a large number of eosinophils, epithelioid cells, foreign body type giant cells, and collagen fibers were aggregated around the mait bodies. Numerous mast cells were also detected in the lesions by toluidine blue staining, and tested positive for tryptase by immunohistochemistry. This may be the first reported case of severe pulmonary acariasis in a Japanese macaque. PMID- 11217073 TI - In addition to the high-density lipoprotein fraction, apolipoprotein C-III is detected in chylomicrons and the very low-density lipoprotein fraction from serum of normolipidemic cows. AB - Apolipoprotein (apo) C-III is a low-molecular-mass protein that is involved in the regulation of the triglyceride metabolism. Except for the hyperlipidemic calf, cattle apoC-III is mainly detected in the high-density lipoprotein (HDL) fraction, and the distribution in chylomicrons (CM) and the very low-density lipoprotein (VLDL) fraction has not yet been clarified. The purpose of the present study was to detect apoC-III in concentrated CM and VLDL fractions to examine whether apoC-III is distributed in the two fractions even in normolipidemic cattle. ApoC-III could be detected by immunoblot analysis in both concentrated cow CM and VLDL fractions, but not in the corresponding calf fractions. These results suggest that apoC-III is distributed in the CM and VLDL fractions, at least in cows, although the concentrations in these fractions are considerably lower than in the HDL fraction. PMID- 11217074 TI - A study of reproductive performance in pregnant, IL-2 receptor beta-chain overexpressed transgenic mice. AB - Relationships between female reproductive performance and uterine natural killer (uNK) cells were investigated in pregnant IL-2 receptor beta-chain overexpressed transgenic (Tg2Rbeta) mice. At 8 days of pregnancy, all fetuses were alive, suggesting that implantation normally occurred in these mice. However, 47% of fetuses were dead at 10 days of pregnancy and at 12 days all fetuses were resorbing, indicating that fetal loss progressed with the advance of pregnancy. The placenta of Tg2Rbeta mice gradually decreased in weight with the advance of pregnancy. At 10 days the placental labyrinth, decidua basalis, and metrial gland in Tg2Rbeta mice were poorly developed, and more uNK cells were found in Tg2Rbeta mice than in the control mice. We propose that Tg2RPbeta mice are the first and interesting model that uNK cells can cause abortion, to clarify the involvement of uNK cell function in female reproductive performance. PMID- 11217075 TI - Conditionally immortalized cell lines as a new in vitro model for the study of barrier functions. AB - Conditionally immortalized brain and retinal capillary endothelial and choroid plexus epithelial cell lines were established from a transgenic rat (Tg rat) and mouse (Tg mouse) harboring the temperature-sensitive simian virus 40 (ts SV 40) large T-antigen. These cell lines exhibit temperature-sensitive cell growth due to the expression of ts SV 40 large T-antigen. Mouse brain (TM-BBB) and rat brain (TR-BBB) and rat retinal (TR-iBRB) capillary endothelial cell lines appear to have a spindle-fiber shaped morphology and exhibit the typical endothelial markers, such as von Willebrand factor and acetylated low-density lipoprotein uptake. These cell lines express in vivo influx and efflux transporters, such as P-glycoprotein (P-gp) and GLUT1, which is capable of 3-O-methyl-D-glucose transport. TM-BBB cells are able to undergo efflux transport of cyclosporin A, which is a substrate for P-gp transport activity. They may also express oatp2 and exhibit dehydroepiandrosterone sulfate and digoxin uptake activity. TR-BBB cells express the mRNA of multidrug resistance associated protein 1 (MRP1) and a large neutral amino acid transporter, which consists of LAT1 and 4F2hc. TR-iBRB cells exhibit pH-dependent L-lactic acid transport activity and express the mRNA of monocarboxylate transporter (MCT) 1 and 2. The choroid plexus epithelial cell line (TR-CSFB) has polygonal cell morphology, expresses the typical choroid plexus epithelial cell marker, transthyretin, and has Na+, K+-ATPase located on the apical side. TR-CSFB cells also exhibit amino acid transport activity which has been observed in vivo. These barrier cell lines established from the Tg rat and Tg mouse have in vivo transport functions and are good in vitro models for drug transport to the brain and retina and as a screen for drugs which might be capable of delivery to the brain and retina. PMID- 11217076 TI - Characterization of a protease responsible for truncated actin increase in neutrophils of patients with Behcet's disease. AB - As described previously (Yamashita S. et al., Biol. Pharm. Bull., 23, 519-522 (2000)), high levels of a truncated actin with an N-terminus of Met-44 were detected in neutrophils of patients with Behcet's disease. Since the increase of the truncated actin in neutrophils of patients may be important for understanding the pathology of Behcet's disease, the mechanism of the truncated actin formation was studied. First, to investigate the presence of a specific protease, which cleaves the actin at the site between Val-43 and Met-44, a peptide with a partial amino acid sequence of actin from the N-terminal Pro-38 to Asp-51 was synthesized as the protease substrate. The synthesized peptide was digested with cytosolic fractions of neutrophils from patients and healthy volunteers, and digestion products were analyzed by C18-reverse phase HPLC. The chromatograms of these samples showed that an endoprotease, which cleaved the peptide at a specific site, was present in cytosolic fractions of neutrophils from patients with Behcet's disease. Then, the effects of various kinds of protease inhibitors on the digestion of the peptide were investigated in order to identify the responsible endoprotease. The digestion of the peptide was suppressed by 4-(2 aminoethyl) benzenesulfonylfluoride (AEBSF, a serine protease inhibitor) and N methoxysuccinyl-Ala-Ala-Pro-Val chloromethylketone (CMK, a polymorphonuclear (PMN)-elastase inhibitor) in the presence of EDTA. Furthermore, PMN-elastase was found to cleave the substrate peptide and actin at the site between Val-43 and Met-44. These results lead to the conclusion that the PMN-elastase is responsible for cleavage of actin at the N-terminal site between Val-43 and Met-44 in neutrophils from patients with Behcet's disease. PMID- 11217077 TI - Protective effect of fluvastatin on degradation of apolipoprotein B by a radical reaction in human plasma. AB - Fluvastatin, which is a synthetic 3-hydroxy-3-methylglutaryl coenzyme (HMG-CoA) reductase inhibitor, its metabolites (M2, M3 and M4) and trolox all inhibited the decrease of apolipoprotein B-100 (apoB) and alpha-tocopherol in a radical reaction of human plasma initiated by Cu2+. The concentrations of fluvastatin, M2, M3, M4 and trolox for 50% inhibition (IC50) of apoB fragmentation were 405, 8.55, 1.75, 305, and 43.4 microM, respectively. The IC50 value of pravastatin, which is another HMG-CoA reductase inhibitor, was 2880 microM, showing that pravastatin is not an effective antioxidant. Although fluvastatin, its metabolites and trolox inhibited the decrease of alpha-tocopherol in a similar manner to that of apoB, pravastatin did not significantly inhibit the decrease of alpha-tocopherol. Since oxidation of low density lipopotein (LDL) is an important step in the initiation and progression of atherosclerosis, fluvastatin may reduce the risk of atherosclerosis not only by lowering plasma cholesterol but also by protecting LDL from oxidation. PMID- 11217078 TI - Experimental administration of estradiol on the colonization of lactobacillus fermentum and escherichia coli in the urogenital tract of mice. AB - The effect of estrogen on the microbial colonization of the urogenital tract is widely discussed, mainly in regard to women with a high incidence of Urinary Tract Infections (UTI). The aim of this work was to study the effect of estradiol on the microbial colonization of lactobacilli and E. coli in mice. Female BALB/c mice were intramuscularly (i.m.) treated with beta-estradiol (one or three doses). The next day, L. fermentum was inoculated intraurethrally with three doses of 10(7) CFU (Colony Forming Units). Later, mice were challenged with uropathogenic E. coli (1 x 10(8) CFU). The hormone levels in sera increased to values 10 times higher than in control animals. Increased differentiation of desquamated vaginal cells and keratinization of the vaginal surface were also observed. The hormonal treatment produced an increased E. coli colonization in the whole tract and a higher level of L. fermentum in kidneys on the 6th day. In mice treated with hormones and lactobacilli, one dose of estradiol was enough to protect animals against the challenge with E. coli. Three doses of estradiol produced a more pronounced protection with a lower number of E. coli. No histological modifications were produced by L.fermentum, while lymphocytic proliferation at submucosal level was observed in E. coli-challenged animals. PMID- 11217079 TI - Characterization of the mouse TFF1 (pS2) gene promoter region. AB - Trefoil peptides (TFFs) with a unique trefoil domain(s) are presumed to function in protection and repair of the gastrointestinal epithelial layer. Three peptide family members are differently distributed in the mouse gastrointestinal tract: TFF1/pS2 specifically in stomach, TFF2/SP mainly in stomach, pancreas and duodenum, and TFF3/ITF in intestine. We cloned and sequenced the mouse TFF1 gene 5'-upstream region by means of the genomic walking procedure. The cloned region was ligated to the luciferase reporter gene and then introduced into mouse gastric surface mucous GSM10 cells which express TFF1 and TFF2. The minimum promoter was located in the region containing the TATA-box between -39 and the transcriptional start site. Further upstream regions stimulated (-2192-- -1630bp, -641-- -243bp, -137-- -39bp) and inhibited (-1630-- -641bp, -243-- -137 bp) luciferase gene expression. These regions as well as short segments conserved in the mouse and human 5'-upstream sequences may be important for modulation of the mRNA level of the TFF1 gene. PMID- 11217080 TI - Identification of the substrates for plasma hyaluronan binding protein. AB - Plasma hyaluronan biding protein (PHBP) is a novel serine protease, which has an amino acid sequence homology to that of hepatocyte growth factor activator (HGFA), and has a similar domain structure to that of urinary plasminogen activator (u-PA), found in human plasma. We searched the PHBP substrate in human plasma by measuring the digested protein bands on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The results showed that fibrinogen and fibronectin were the major substrates of PHBP. PHBP cleaved the alpha-chain at multiple sites and the beta-chain between lysine53 and lysine54 but not the gamma-chain of fibrinogen. Therefore, PHBP did not initiate the formation of the fibrin clot and did not cause the fibrinolysis directly. PHBP did not cleave (activate) prothrombin and plasminogen, but it converted the inactive single chain urinary plasminogen activator to the active two chain form. PMID- 11217081 TI - Identification of zinc finger proteins bound to a silencer region in the rat glutathione transferase P gene. AB - The rat glutathione transferase P (GST-P) gene is strongly induced during chemical hepatocarcinogenesis, whereas mRNA of this gene is rarely expressed in normal rat liver. We previously identified a silencer region in the promoter of this gene. This silencer has several DNA binding sites and at least three proteins (Silencer factor A, -B, and -C (SF-A, SF-B, and SF-C)) bind to these sites. We previously cloned and characterized the Nuclear Factor 1 (NF1) family and the CCAAT/enhancer-binding protein (C/EBP) family as SF-A and SF-B, respectively. However, SF-C which binds to GST-P silencer 2 (GPS2) remains to be cloned. By screening using yeast one-hybrid system, several zinc finger proteins were identified as a candidate of SF-C. The gel-mobility shift analyses showed that BTEB2, EZF, LKLF, TFIIIA, TIEG1, and novel zinc finger protein MZFP bound to GPS2 with different affinities. Several proteins of these are known to be transcriptional activators or repressors, suggesting that zinc finger proteins bind to GPS2 and regulate GST-P expression in the rat liver. PMID- 11217082 TI - Demonstration of inhibitory effect of oral shark cartilage on basic fibroblast growth factor-induced angiogenesis in the rabbit cornea. AB - Several angiogenic inhibitors have been obtained from shark cartilage, some of these are currently in clinical trials for assessment of safety and therapeutic efficacy in humans. Still, shark cartilage taken orally is commonly used in alternative and complimentary medicine for various ailments including serious diseases such as cancer. However, only few studies of oral shark cartilage have demonstrated pharmacological effects in experimental animals or patients, to indicate safe doses with sufficient bioavailability. In the present study we demonstrated the antiangiogenic properties of oral shark cartilage in the rabbit cornea model. Slow-release, polymethylmetacrylate pellets containing basic fibroblast growth factor (bFGF) were surgically implanted in the rabbit cornea to stimulate neovascularization scored by stereo microscopy. Powdered shark cartilage (PSC; commercial product) was tested orally along with a water-soluble fraction (WSF) of this cartilage product which was tested by local application. Animals were treated with oral dosages of 100 mg/kg PSC or 200 mg/kg thalidomide as positive control. Pellets containing WSF (50, 100 or 200 microg/pellet) or bFGF-inhibitor pentosan polysulfate were implanted adjacent to the bFGF pellet. Oral shark cartilage inhibited bFGF-induced angiogenesis, as did oral thalidomide, in this in vivo model. WSF and pentosan polysulfate was shown to block neovascularization in the cornea when applied locally. This study demonstrates that in the rabbit, oral shark cartilage appears to produce systemic levels of angiogenesis inhibitors that can exert their effect at the cornea. PMID- 11217083 TI - Mechanism of superoxide generation system in indomethacin-induced gastric mucosal injury in rats. AB - We studied the mechanism of the superoxide generation system in indomethacin induced gastric mucosal injury. First, 10 mM indomethacin had no direct effect on xanthine oxidase (XOD) activity. Next, we found that NADPH oxidase activity in polymorphonuclear leukocytes (PMN) of peripheral blood was significantly increased 6 h after administration of indomethacin. This phenomenon was inhibited by the injection of the NADPH oxidase inhibitor, diphenylene iodonium chloride (DIC). Activation of NADPH oxidase caused the component, p47phox to be translocated to the plasma membrane. Since indomethacin did not directly activate NADPH oxidase, we sought another route of activation of PMN. As IL-1 and TNF alpha play in the inflammation, we examined these cytokines in this study. TNF alpha was not detected but IL-1 was increased significantly 30 min after administration of indomethacin. PMID- 11217084 TI - Effects of two saponins extracted from the polygonatum Zanlanscianense pamp on the human leukemia (HL-60) cells. AB - Two saponins, methyl protodioscin and dioscin, were extracted from the root of Polygonatum Zanlanscianense Pamp. One of them, dioscin exerted significant inhibitory effects on the growth of the human leukemia cell HL-60, inducing differentiation and apoptosis. HL60 cells were induced mainly along the granulocytic lineage. In addition, we have found that dioscin affects many cancer cells. These studies may have important significance in treating related cancers. PMID- 11217085 TI - Effects of paint thinner exposure on serum LH, FSH and testosterone levels and hypothalamic catecholamine contents in the male rat. AB - We have investigated the effects of thinner inhalation on serum LH, FSH and testosterone levels together with changes in hypothalamic catecholaminergic system in the male rat. A control group inhaled normal air ventilation. The remaining animals were divided into two groups and exposed to paint thinner in a glassy cage for 15 or 30 d. Toluene concentration (the largest constituent in thinner, 66%) was set at 3000 ppm in the inhalation air. At the end, all animals were decapitated and blood samples obtained. Serum LH and FSH levels were measured by RIA and testosterone by enzyme immunoassay. Following removal of brains on dry ice, medial preoptic area, suprachiasmatic nucleus, median eminence and arcuate nucleus were isolated by micropunch technique. Noradrenaline, 3,4 dihydroxyphenylglycol (DHPG) and dopamine concentrations of these hypothalamic areas were determined by HPLC-ECD. Fifteen-day thinner inhalation significantly suppressed serum LH and testosterone levels in parallel (p<0.001) compared to control group values (LH: 0.77+/-0.07; testosterone: 2.67+/-0.39). Thirty-day exposure markedly decreased LH levels (p<0.001), but surprisingly had no significant effect on testosterone. Serum FSH levels were not significantly altered in either group. Thinner inhalation for 15 or 30 d did not cause any significant change in noradrenaline, DHPG or dopamine concentrations in the hypothalamic regions examined (except in the arcuate nucleus). These results suggest that paint thinner has an anti-gonadotropic effect and may cause long term endocrine disturbances in the male. It is thought that the hypothalamic catecholaminergic system is not involved in thinner inhibition of LH and testosterone secretion. PMID- 11217086 TI - Savinin, a lignan from Pterocarpus santalinus inhibits tumor necrosis factor alpha production and T cell proliferation. AB - Two lignans were isolated from the heartwood of Pterocarpus santalinus by activity-guided fractionation and investigated for their biological properties and molecular mechanism of action. On the basis of their spectroscopic data, these compounds were identified as savinin (1) and calocedrin (2), dibenzyl butyrolactone-type lignan compounds having an alpha-arylidene gamma-lactone structure. These lignans significantly inhibited tumor necrosis factor (TNF)-a production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and T cell proliferation elicited by concanavalin (Con A), without displaying cytotoxicity. The molecular inhibitory mechanism of compound 1 was confirmed to be mediated by the non-polar butyrolactone ring, according to a structure-relationship study with structurally related and unrelated compounds, such as arctigenin (a dibenzyl butyrolactone type lignan), eudesmin (a furofuran type lignan), isolariciresinol (a dibenzylbutane type lignan), and cynaropicrin (a sesquiterpene lactone). The results suggest that savinin may act as an active principle in the reported biological activities of P. santalinus, such as antiinflammatory effect, by mediation of the butyrolactone ring as a valuable pharmacophore. PMID- 11217088 TI - High-Performance liquid chromatographic analysis of lactone and hydroxy acid of new antitumor drug, DX-8951 (exatecan), in mouse plasma. AB - A sensitive high-performance liquid chromatographic (HPLC) method has been developed and validated for the determination of lactone and total drug (lactone plus hydroxy-acid) of DX-8951 in mouse plasma. Solid-phase extraction by C18 cartridge separated lactone from total drug of DX-8951. Analysis was performed using a reverse-phase ODS column with a mobile phase consisting of acetonitrile/0.05 M potassium dihydrogen phosphate (pH 3) (18: 82, v/v) at a flow rate of 1 ml/min. The limits of quantitation of lactone and total drug were 3 ng/ml in plasma and a linear range of determination were observed over the concentration of 3 to 500 ng/ml. This method was applied to pharmacokinetic study in male mice treated with a single intravenous administration of either lactone or hydroxy-acid of DX-8951. The plasma concentrations of lactone from 2 to 6 h after dosing were similar regardless of the form of DX-8951 administered. PMID- 11217087 TI - Suppressive effects of Perilla frutescens on mesangioproliferative glomerulonephritis in rats. AB - Leaves of Perilla frutescens var. crispa DECNE. (perilla, Labiatae) are used as a garnishing vegetable in East Asian countries as well as an herbal medicine prescribed in Kampo medicines such as Saiboku-to. A previous in vitro study revealed that a decoction of perilla leaves inhibits the proliferation of murine cultured mesangial cells. In the present study, we evaluated the in vivo anti proliferative effects of a perilla decoction using rat mesangio-proliferative glomerulonephritis induced by an intravenous injection of rabbit anti-rat thymocyte serum (ATS). Leaves of perilla were boiled, and the decoction was orally administered to the rats as drinking water at doses of 100 and 500 mg/kg/d from the day of ATS-injection (day 0) to day 8, when rats were sacrificed. In the histological evaluation, the total number of glomerular cells, proliferating cell nuclear antigen (PCNA) positive cells, and macrophage/monocyte antigen-positive cells in the glomerulus, was significantly decreased in perilla-treated rats. A significantly lower level of proliferation was induced by the serum of the perilla-treated rats than by that of the controls. These results suggest that the perilla decoction suppresses the proliferation of mesangial cells in vivo by an inhibition of the glomerular infiltration of macrophage/monocytes and of the production of circulating growth factors. PMID- 11217090 TI - Extract from Serenoa repens suppresses the invasion activity of human urological cancer cells by inhibiting urokinase-type plasminogen activator. AB - We used three human urological cancer cell lines, PC-3, LNCaP and SKRC-1, to investigate the effects of the extract from Serenoa repens (Palmae) on tumor cell invasion. The invasion activity of these cell lines was determined in vitro using a Transwell cell-culture chamber. The invasion activity of PC-3 cells into Matrigel was effectively suppressed by the extract at the concentration range of 1-10 microg/ml, while that of LNCaP and SKRC-1 cells was unaffected by the extract. The extract did not affect the viability, adhesion ability, or motility of the cell lines. uPA is more strongly expressed on the membrane fraction of PC 3 cells than that of LNCaP or SKRC-1 cells. The purified uPA activity is inhibited by the extract from S. repens in a dose-dependent manner, suggesting that the suppression of PC-3 cell invasion by the extract is based on an inhibition of the uPA activity which is necessary for tumor cell invasion. These data suggest that the extract from S. repens specifically inhibits the uPA activity and may therefore be useful for the therapeutic treatment of prostate cancer. PMID- 11217089 TI - Purification and characterization of antithrombotics from Syzygium aromaticum (L.) MErr. & PERRY. AB - Two antithrombotic polysaccharides with relatively high molecular weight (HMW) and low molecular weight (LMW) were isolated from the flower buds of Syzygium aromaticum (L.) MERR. & PERRY (clove) by anion-exchange chromatography, hydrophobic interaction column chromatography and size exclusion chromatography (LMW: EC-2B-IIIa-2, M.W. ca. 34000; HMW: EC-2C-Ia-2, M.W. ca. 103000). The LMW polysaccharide was mainly composed of Rha, Gal, GalA and Ara (molar %: 24.1, 18.9, 18.0 and 17.9, respectively) with 10.8% of sulfate and 18.2% of protein. The HMW fraction consisted of Ara, Gal, Glc and Rha (molar %: 26.0, 23.7, 17.5 and 12.4, respectively) with 15.4% of sulfate and 8.0% of protein. Both polysaccharides had the backbone of type I rhamnogalacturonan and the side chain of arabinan. Also, most of the sulfates were attached at the position 6 of 3 linked galactosyl residues. Compared to the antithrombotic activity of the HMW fraction (plasma clotting time of 145 s in APTT assay), the LMW fraction displayed a slightly low activity (90 s). However, animal studies indicated that crude LMW polysaccharide did not show acute toxicity, while the acute LD50 of the HMW fraction was approximately 2-fold lower than that of heparin. PMID- 11217091 TI - Heparin-Affinity of human extracellular-superoxide dismutase in the brain. AB - Extracellular-superoxide dismutase (EC-SOD) is one of the three SOD isozymes in humans and has affinity for heparin-like sulfated glycosaminoglycans in the extracellular matrix. The C-terminal portion of EC-SOD is responsible for the heparin-affinity of this enzyme, but this portion should be a target of proteinases. Recently, Oury et al. reported that EC-SOD is localized within the cytoplasm of neuronal cells, while this enzyme is found in the extracellular matrix in most other tissues. It has been speculated that the heparin-binding domain of EC-SOD in the brain is sensitive to proteolysis, which may result in a loss of extracellular immunoreactivity. This study was performed to investigate the heparin-affinity of EC-SOD in the human brain. We found that human EC-SOD in brain tissue has high heparin-affinity similar to that in the umbilical cord. Moreover, heparin-affinity of EC-SOD in brain homogenate was not decreased by incubation at 37 degrees C for 72 h. The proteolytic activity in brain homogenate might be less than that in umbilical cord homogenates. The intracellular localization of EC-SOD could contribute to its slow clearance from the brain and maintenance of its physiological functions in the brain. PMID- 11217092 TI - Effects of Ninjin-to on levels of brain-gut peptides (motilin, vasoactive intestinal peptide, gastrin, and somatostatin) in human plasma. AB - We examined the effects of Ninjin-to, a traditional Chinese (Kampo) medicine, on the levels of brain-gut peptides (motilin, vasoactive intestinal peptide (VIP), gastrin, and somatostatin) in plasma from healthy subjects. A single oral administration of Ninjin-to, at a dose of 6.0 g, caused significant increases in plasma motilin levels at 40 to 90 min and somatostatin levels at 20 to 90 min, compared with a placebo treated group. Transient elevations of gastrin levels in the placebo group were inhibited by administration of Ninjin-to, but the medicine did not alter the levels of VIP. In conclusion, these results suggest that pharmacological effects of Ninjin-to on gastrointestinal functions closely relate to changes of motilin, gastrin, and somatostatin-immunoreactive substance levels in human plasma. PMID- 11217093 TI - Expression of a small heat shock protein 27 (HSP27) in mouse skin tumors induced by UVB-irradiation. AB - We investigated the expression of heat shock protein 27 (HSP27) at intermediate stages of a cutaneous tumor induced by UVB-irradiation stress (290-380 nm, max. 312 nm) using an immunostaining method. After 15-20 weeks of chronic exposure to UVB irradiation at a dose of 2 kJ/m2, HSP27 was found in the upper cell layers of bowenoid multilayers of epidermis, in areas of the lesions where normal stratification seems to be conserved. After 25 weeks, HSP27 was weakly expressed in squamous cell carcinoma (SCC). The HSP27 distribution patterns during cutaneous tumor progression resemble that of cytokeratin 10, a differentiation marker in keratinocytes. In SCC, a low degree of HSP27 expression was detected in the well-differentiated carcinomatous areas, but not in the poorly differentiated areas. These results indicate that the level of HSP27 decreases significantly as epithelial carcinoma growth progresses upon UVB-exposure. The expression of HSP27 may be associated with the onset of skin keratinocyte differentiation, but not with progression of SCC. PMID- 11217094 TI - Release of intermediate reactive hydrogen peroxide by macrophage cells activated by natural products. AB - By determining the hydrogen peroxide (H2O2) released in cultures of peritoneal macrophage cells from Swiss mice, we evaluated the action of 27 vegetable compounds (pristimerin, tingenone, jatrophone, palustric acid, lupeol, cladrastin, ocoteine, boldine, tomatine, yohimbine, reserpine, escopoletin, esculine, plumericin, diosgenin, deoxyschizandrin, p-arbutin, mangiferin, and others) using a 2 mg/ml solution of each compound (100 microg/well). Macrophages are cells responsible for the development of the immunological response reaction, liberating more than one hundred compounds into the extracellular environment. Among these are the various cytokines and the intermediate compounds of nitrogen (NO) and oxygen (H2O2). This coordinated sequence of biochemical reactions is known as the "oxidative burst." When we compared the results with those obtained with zymosan (an important stimulator of H2O2) we observed that the compounds showing the highest activity were substances 2 (tingenone), 16 (reserpine) and 20. Other substances such as compounds 1, 4, 5, 6, 8, 12, 13, 14, 15, 17, 19, 23, 24, 26, and 27 also showed a certain activity, but with less intensity than the aforementioned ones. Compounds 3, 7, 9, 10, 11, 18, 21, 22 and 25 presented no activity. These results suggest that natural products (mainly tingenone and reserpine and others) with different chemical structures are strong immunological modulators. However, further tests are needed to determine the 'oxidative burst' in future studies. PMID- 11217095 TI - Biodegradation and drug release of chitosan gel beads in subcutaneous air pouches of mice. AB - Chitosan (CS) gel beads were prepared in 10% amino acid solution (pH 9) and implanted into air pouches (AP) prepared subcutaneously on the dorsal surface of mice. No inflammatory response was observed, and degradation of the beads in the AP increased as their degree of deacetylation decreased. Degradation could be altered by changing the nature of the CS or by increasing the CS concentration. The release of prednisolone (PS) in vivo from CS gel beads was similar to the release in vitro. When a suspension of PS was injected into the AP, the PS had almost completely disappeared 24 h after injection. Retention of PS in the AP was not increased by using a viscous CS solution. Alginate (Alg) gel beads, which were not degraded, released PS slowly into the AP over 3d. The in vitro release profile of PS using 1% CS (deacetylation: 70% (7B) and 80% (8B)) and 1.5% CS (deacetylation: 90% (9B)) gel beads was similar to that with Alg gel beads. However, the in vivo release of PS was affected by the degradability of the gel beads. CS7B and 8B (1%) gel beads had released PS into the AP earlier than 3 d according to their rate of degradation. CS9B (1.5%) gel beads were not degraded after 3 d and went on to release PS into the AP for 3 d similar to the release profile of Alg gel beads. CS9B (2%) gel beads were also not degraded after 3 d and the release of PS from these beads into the AP was sustained; 76% and 27% of administered PS remained in the gel beads after 1 and 3 d, respectively. Therefore, degradation and drug release of CS gel beads can be controlled by changing the structure of the gel matrix, which appears to make these beads a promising biodegradable vehicle for sustained drug delivery. PMID- 11217096 TI - Formulation design of ointment base suitable for healing of lesions in treatment of bedsores. AB - We intended to develop a desired ointment base suitable for treatment of bedsores including the proliferation of granulation and epidermis. The main bedsore bacteria detected in our hospital were S. aureus in gram-positive coccus and P. aeruginosa in gram-negative bacillus. As the macrogol ointment (MO) was found to have bactericidal effects on these bacteria, MO was adopted as the base for the objective ointment. To improve the properties of the ointment base such as regulating the humidity of the exudation and controlling the release of antibiotics formulated in the ointment, co-formulating effects of various additives to MO were evaluated. The sustained release function of the ointment base was obtained by adding hydrophilic petrolatum (HP) to MO. However, the resultant ointment was found to have a poor humidity regulating property. On the other hand, MO containing 5% of hydroxypropyl cellulose (HPC) showed both the humidity regulating and the controlled drug releasing properties. It was considered that HPC particles dispersed in the ointment could be swelled by absorbing water to form a gel network. The curd tension meter tests for the ointments prepared with the various polymers showed that the MO-HPC base, which showed the highest sustained drug releasing property, was found to have the highest hardness. This result means that HPC formulated into the base forms the most rigid gel structure to resist the erosion of the ointment and to control the drug release. PMID- 11217097 TI - Preparation of rapidly disintegrating tablet using new types of microcrystalline cellulose (PH-M series) and low substituted-hydroxypropylcellulose or spherical sugar granules by direct compression method. AB - To decrease the sensation of roughness when a tablet, which is rapidly disintegrated by saliva (rapidly disintegrating tablet), is orally taken, we prepared rapidly disintegrating tablets using microcrystalline cellulose (Avicel PH-M series), a new type of pharmaceutical excipient that is spherical and has a very small particle size (particle size, 7-32 microm), instead of conventional microcrystalline cellulose (PH-102) used in the formulation of tablets containing acetaminophen or ascorbic acid as model drugs for tableting study. Tablets (200 mg) prepared using spherical microcrystalline cellulose, PH-M-06, with the smallest particle size (mean value, 7 microm) had sufficient crushing tolerance (approximately, 8 kg) and were very rapidly, disintegrated (within 15 s) when the mixing ratio of PH-M-06 to low-substituted hydroxypropylcellulose (L-HPC) was 9:1. Sensory evaluation by volunteers showed that PH-M-06 was superior to PH-102 in terms of the feeling of roughness in the mouth. Consequently, it was found that particle size is an important factor for tablet preparation using microcrystalline cellulose. It is possible to prepare drugs such as acetaminophen and ascorbic acid (concentration of approximately 50%) in the tablet form using PH-NM-06 in combination with L-HPC as a good disintegrant at a low compression force (1-6 kN). To solve the problem of poor fluidity in the preparation of these tablets, we investigated the use of spherical sugar granules (Nonpareil, NP-101 (sucrose and starch, composition ratio of 7:3), NP-103 (purified sucrose), NP-107 (purified lactose) and NP-108 (purified D-mannitol)). Rapidly disintegrating tablets can be prepared by the direct compression method when suitable excipients such as fine microcrystalline cellulose (PH-M-06) and spherical sugar granules (NP) are used. PMID- 11217098 TI - Melt pelletization of a hygroscopic drug in a high shear mixer. Part 3. Effects of binder variation. AB - Melt pelletization experiments with sodium valproate as a hygroscopic drug were performed in a laboratory scale high shear mixer. In the current part, the effect of altering the binder liquid properties (using different binders, varying the temperature, or adding highly dispersed silicon dioxide to the molten binder) on the pellet size, size distribution and the growth rate was studied. Three meltable binders, namely glycerol monostearate (GMS), hydrated castor oil (HCO), and polyethylene glycol (PEG), were included in the study. Two series of experiments with GMS or HCO showed a higher granule growth rate with decreasing binder viscosity. Also, increases in the granule growth rate were observed for all meltable binders tested, when the binder amount and the impeller speed were increased. Factorial designs with all three binders were performed under the same conditions. In these experiments, no correlation existed between the granule growth rate and the viscosity of the different binders. The different granule growth rate, however, was mainly attributed to the different solubility of sodium valproate in the binder liquid used. Higher solubility increased the volume of the binder liquid and, accordingly, the granule growth rate. Taking the amount of dissolved drug into account, the granule growth rates of GMS and PEG were comparable. However, HCO displayed a lower granule growth rate, which might be related to its low adhesion tension. During melt pelletization in a high shear mixer the solubility of the drug in the molten binder strongly influences the pelletization process. PMID- 11217099 TI - A prodrug of NMDA/glycine site antagonist, L-703,717, with improved BBB permeability: 4-acetoxy derivative and its positron-emitter labeled analog. AB - 4-Acetoxy derivative (1) of L-703,717, a high-affinity (IC50=4.5 nM) antagonist for the glycine site of NMDA receptors, was synthesized and its brain uptake was examined using a carbon-11 labeled analog ([11C]1). Initial radioactivity in the brain after intravenous injection of [11C]1 was a 2-fold that of [11C]L-703,717 in mice. Rapid bioconversion of [11C]1 into [11C]L-703,717 was demonstrated by metabolite analyses of rat brain after [11C]1 injection. Ex vivo autoradiography of [11C]1 in rat brain showed the same cerebellar localization of radioactivity as [11C]L-703,717. These results indicate that 1 is a promising pharmacological tool as a prodrug of L-703,717 with improved BBB permeability. PMID- 11217100 TI - Studies on the constituents of the leaves of Morus alba L. AB - Two novel prenylflavanes (1, 2) and a glycoside (3) of 1 were isolated along with six known compounds, isoquercitrin (4), astragalin (5), scopolin (6), skimmin (7), roseoside II (8) and benzyl D-glucopyranoside (9), from the leaves of Morus alba. The inhibitory activities of compounds 1, 2 and 3 on the oxidation of human low density lipoprotein (LDL) were investigated. PMID- 11217101 TI - Analgesic components of saposhnikovia root (Saposhnikovia divaricata). AB - By activity-oriented separation using the writhing method in mice, the analgesic components of Saposhnikovia root (Saposhnikovia divaricata Schischkin; Umbelliferae) were identified to be chromones, coumarins, polyacetylenes and 1 acylglycerols. Two new components, divaricatol and (3'S)-hydroxydeltoin, were also isolated. The most potent analgesia was observed in chromones such as divaricatol, ledebouriellol and hamaudol, which inhibited writhing inhibition at an oral dose of 1 mg/kg in mice. Acylglycerols also showed inhibition significantly at a dose of 5 mg/kg. In some pharmacological tests using sec-O glucosylhamaudol, the compound showed analgesia by the tail pressure and the Randall & Selitto methods, and its writhing inhibition was not reversed by naloxone. PMID- 11217102 TI - Six new withanolide-type steroids from the leaves of Solanum cilistum. AB - Six new withanolide-type steroids, designated cilistols v, t, i, j, y and w (1-6, respectively), were obtained from the leaves of Solanum cilistum. Their respective structures were characterized by spectroscopic means as follows: Cilistol v (1) was (22R,24Z)-1alpha,3beta,22,26-tetrahydroxyergost-5,24-diene 26 O-beta-D-glucopyranoside, which is regarded as the precursor of other withanolide type steroids included in this title plant. Cilistol t (2) was (22R,24S,25R,26S) 24,25;22,26-diepoxy-1alpha,3beta,26-trihydroxyergost-5-ene 26-O-beta-D glucopyranoside, and cilistols j (3) and i (4) corresponded to the substances probably formed by the cleavage of the epoxy ring at C-24 and 25 of 2. Cilistol y (5) was 3-O-sulphonyl (22R,24S,25R,26R)-1-oxo-24,25; 22,26-diepoxy 3beta,17alpha,26-trihydroxyergost-5-ene 26-O-beta-D-glucopyranoside, and cilistol w (6) corresponded to the substance obtained by the fission of the epoxy ring at C-24 and 25 of 5. The occurrence of these withanolide type steroids from Solanum genera is rare and worthy of note. PMID- 11217103 TI - Analysis of electron spin resonance spectra of alkyl spin labels in excised guinea pig dorsal skin, its stratum corneum, delipidized skin and stratum corneum model lipid liposomes. AB - The electron spin resonance (ESR) spectra of alkyl spin labels were observed in the excised guinea pig dorsal skin, its stratum corneum, delipidized skin and stratum corneum model lipid liposomes. The spectrum of 5-doxylstearic acid (5-NS) in the stratum corneum and order parameter obtained from the spectrum, indicated that the spin label was present in highly ordered lipid lamella. On the other hand, the spectrum of methyl ester of 5-NS (5-NMS) and its apparent rotational correlation time calculated from the spectrum, showed only a weakly immobilized component in the stratum corneum as well as in the whole excised skin. The ester spin label seemed to be scarcely present in the rigid lipid lamella, but mainly in the relatively fluid environment. On the other hand, cationic alkyl spin labels showed quite different spectra depending on their alkyl chain lengths. Long-chain 4-(N,N-dimethyl-N,-pentadecyl)ammonium-2,2,6,6-tetramethylpiperidine-1 oxyl (CAT-15) seemed to be present in the protein region of the stratum corneum as we recently reported, whereas hydrophilic quaternary ammonium spin label 4 trimethylammonium-2,2,6,6-tetramethylpiperidine-1-oxyl (CAT-1) seemed to be present in the bulk water of the skin, even in delipidized skin. These findings indicated that the different interaction and different localization of the alkyl spin labels depended on their electronic charge as well as their alkyl chain lengths. PMID- 11217104 TI - Preparation of a novel aggregate like sugar-ball micelle composed of poly(methylglutamate) and poly(ethyleneglycol) modified by lactose and its molecular recognition by lectin. AB - We report the preparation and characteristics of a novel micellar aggregate of an amphiphilic diblock copolymer, poly(methylglutamate) (PMG)-poly(ethyleneglycol) (PEG), whose terminus was modified by lactose lactone (LA). Due to the terminal LA moiety, this aggregate could be specifically recognized by RCA120 lectin. PMG PEG-LA was synthesized by polymerizing the N-carboxy anhydride of L-glutamic acid gamma-methyl ester with H2N-PEG-LA as a polymerization initiator. By applying a fluorescence method using pyrene as a probe molecule, we found that PMG-PEG-LA could form the aggregate in aqueous solution. Fluorescence measurements showed that the critical aggregation concentration (C.A.C.) was 1.1 x 10(-5) M. The average diameter of the aggregate was 220 nm at 25 degrees C, as determined by the dynamic light scattering method. Circular dichroism measurements for the aggregate solution showed that the PMG residue took an alpha-helical structure, and that they associated to constitute the hydrophobic core of the aggregate. By adding RCA120 lectin to the aggregate solution, the turbidity of the solution increased rapidly, due to association of the aggregates. This implies that the aggregate could be recognized by lectin, and also suggests that sugar residues locate at the surface of the aggregates. From these findings, we concluded that the PMG-PEG-LA molecules form an aggregate like a "sugar ball" micelle, whose surface is covered by the sugar moieties. Application of the present aggregate system as a drug carrier is briefly discussed. PMID- 11217105 TI - New antifungal 1,2,4-triazoles with difluoro(substituted sulfonyl)methyl moiety. AB - New 1,2,4-triazoles (2) having a difluoro(substituted sulfonyl)methyl moiety were designed and synthesized via alpha,alpha-difluoro-alpha-(substituted thio)acetophenones (3). Compounds (2) showed potent antifungal activities against C. albicans, C. krusei, A. flavus and A. fumigatus in vitro and against C. albicans in vivo for oral and i.v. administrations. Especially, (-)-2a, (-)-2b and (-)-2d showed potent antifungal activities. PMID- 11217106 TI - Triterpenes and lignans from Artemisia caruifolia and their cytotoxic effects on meth-A and LLC tumor cell lines. AB - One new triterpene, 3beta-hydroxy-29-norcycloart-24-one (1), and four new lignans, caruilignans (2-5), together with six known compounds were isolated from the aerial part of Artemisia caruifolia BUCH.-HAM. ex TOXB. Their structures were determined by various spectroscopic means. Most of the isolated lignans were moderately cytotoxic to Meth-A cells with ED50 values of 5-10 microg/ml, but not to Lowis lung carcinoma (LLC) cells. An oxime derivative of 1 showed more potent cytotoxic activity against Meth-A and LLC cells than the original triterpene 1. PMID- 11217107 TI - Phosphodiesterase 4 isoenzyme inhibitory activity of 3-phenylxanthines and 4 pheny. AB - On the basis of our study on the structure-activity relationships of 1,3,7 alkylxanthines and condensed-purines on cAMP-phosphodiesterase 4 (PDE 4) isoenzyme inhibitor, we investigated the synthesis and the inhibitory activity of 3-phenylxanthine and 4-phenyl[i]condensed-purine derivatives. Xanthines and condensed-purines with the phenyl group exhibited potent and selective PDE 4 inhibitory activity. PMID- 11217108 TI - Mechanistic studies on the biomimetic reduction of tetrahydroxynaphthalene, a key intermediate in melanin biosynthesis. AB - 1,3,6,8-Tetrahydroxynaphthalene (T4HN) is an aromatic polyketide, serving as a general precursor of fungal melanin. Melanin biosynthesis involves two consecutive deoxygenations of T4HN, consisting of the reduction of a phenolic carbon followed by dehydration. The first reduction to produce scytalone was studied in a biomimetic reduction with sodium borohydride. The reduction required a strong alkaline condition, leading to the tautomerization of T4HN to a reactive species whose structure was clarified by NMR spectroscopy. PMID- 11217109 TI - Geranylgeranyl diphosphate synthase from Scoparia dulcis and Croton sublyratus. Plastid localization and conversion to a farnesyl diphosphate synthase by mutagenesis. AB - cDNAs encoding geranylgeranyl diphosphate synthase (GGPPS) of two diterpene producing plants, Scoparia dulcis and Croton sublyratus, have been isolated using the homology-based polymerase chain reaction (PCR) method. Both clones contained highly conserved aspartate-rich motifs (DDXX(XX)D) and their N-terminal residues exhibited the characteristics of chloroplast targeting sequence. When expressed in Escherichia coli, both the full-length and truncated proteins in which the putative targeting sequence was deleted catalyzed the condensation of farnesyl diphosphate and isopentenyl diphosphate to produce geranylgeranyl diphosphate (GGPP). The structural factors determining the product length in plant GGPPSs were investigated by constructing S. dulcis GGPPS mutants on the basis of sequence comparison with the first aspartate-rich motif (FARM) of plant farnesyl diphosphate synthase. The result indicated that in plant GGPPSs small amino acids, Met and Ser, at the fourth and fifth positions before FARM and Pro and Cys insertion in FARM play essential roles in determination of product length. Further, when a chimeric gene comprised of the putative transit peptide of the S. dulcis GGPPS gene and a green fluorescent protein was introduced into Arabidopsis leaves by particle gun bombardment, the chimeric protein was localized in chloroplasts, indicating that the cloned S. dulcis GGPPS is a chloroplast protein. PMID- 11217110 TI - Compositional analysis of copoly (DL-lactic/glycolic acid) (PLGA) by pyrolysis gas chromatography/mass spectrometry combined with one-step thermally assisted hydrolysis and methylation in the presence of tetramethylammonium hydroxide. AB - Rapid and precise compositional analysis of copoly (DL-lactic/glycolic acid) (PLGA) was performed by pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) combined with one-step hydrolysis and methylation in the presence of tetramethylammonium hydroxide (TMAH). Pyrolysis of PLGA with TMAH gave two characteristic products, derivatives of DL-lactic acid and glycolic acid, which directly reflect the average molar composition of PLGA. The analytical results for PLGA samples with various compositional ratios were in good agreement with those obtained by 1H-NMR spectrometry, and the precision was satisfactory. PMID- 11217112 TI - Radical cyclization in heterocycle synthesis. 12. Sulfanyl radical addition addition-cyclization (SRAAC) of unbranched diynes and its application to the synthesis of A-ring fragment of 1alpha,25-dihydroxyvitamin D3. AB - Sulfanyl radical addition-addition-cyclization (SRAAC) of unbranched diynes proceeded smoothly to give cyclized exo-olefins, while the sulfanyl radical addition-cyclization-addition (SRACA) of diynes having a quaternary carbon gave cyclized endo-olefins. This method was successfully applied to the synthesis of A ring fragment of 1alpha,25-dihydroxyvitamin D3. PMID- 11217111 TI - Asymmetric synthesis of a 3-acyltetronic acid derivative, RK-682, and formation of its calcium salt during silica gel column chromatography. AB - RK-682 was reported to be a potent protein tyrosine phosphatase inhibitor. We found that (R)-3-hexadecanoyl-5-hydroxymethyltetronic acid (1) was easily converted to its calcium salt during column chromatography on Silica gel 60, and this calcium salt was identical to RK-682 originally isolated from a natural source. Here we report details of the asymmetric synthesis of (R)-1 and its conversion to the calcium salt. Fast atom bombardment mass spectrometric (FAB-MS) analysis of the free and calcium salt forms of RK-682 is also reported. PMID- 11217113 TI - Antioxidative and 5-lipoxygenase inhibiting activities of novel bis(4-hydroxy 2,3,5-trimethylphenoxy)alkyl derivatives. AB - Novel bis(4-hydroxy-2,3,5-trimethylphenoxy)alkyl derivatives were synthesized and evaluations were made of their inhibiting action on Fe3+-ADP induced lipid peroxidation in rat liver microsome and reducing action on alpha,alpha-diphenyl beta-picrilhydrazyl (DPPH), a stable radical, in addition to their inhibiting action on 5-lipoxygenase (5-LO), an enzyme that synthesizes leukotrienes. We performed a structure-activity correlation study on these derivatives. A strong Fe3+-ADP induced lipid peroxidation preventing activity was observed for the derivatives with an odd number of methylene groups including 1,3-bis(4-hydroxy 2,3,5-trimethylphenoxy)propane (3b) and 3a. No change in the DPPH reducing activity was found with change in the number of methylene groups. 5-LO inhibiting activity among the derivatives was the highest for 1,6-bis(4-hydroxy-2,3,5 trimethylphenoxy)hexane (3e). MM2 calculations were performed to find a stable steric structure for the derivatives, and 1,5-bis(4-hydroxy-2,3,5 trimethylphenoxy)pentane (3d) showed a strong activity in both antioxidative action and 5-LO inhibiting action. PMID- 11217114 TI - Pharmacokinetics of acetaminophen from rapidly disintegrating compressed tablet prepared using microcrystalline cellulose (PH-M-06) and spherical sugar granules. AB - The aim of the present study was to evaluate the bioavailability of a drug from rapidly disintegrating tablets prepared using fine spherical crystalline cellulose (PH-M-06) and spherical sugar granules (Nonpareil, NP). Rapidly disintegrating tablets containing acetaminophen as the model drug in combination with a mixture of NP-108 (purified n-mannitol) and PH-M-06 were prepared. Plasma concentration profiles and pharmacokinetic parameters of acetaminophen in rabbits were investigated after oral administration of the prepared tablets. No significant difference in Cmax and AUC(0-infinity) of acetaminophen between rapidly disintegrating tablets and conventional tablets was observed after direct administration of these tablets into the stomach of rabbits. However, tmax (15 min) of acetaminophen from rapidly disintegrating tablets was significantly (p<0.05) shorter than that from conventional tablets (130 min). The same tmax was observed for rapidly disintegrating tablets and solution. When suitable excipients such as fine spherical microcrystalline cellulose (PH-M series) and spherical sugar granules (NP series) were used, rapidly disintegrating tablets could be prepared by the conventional direct compression method. According to the results of moment analysis, the mean residence time (MRT) obtained between both rapidly disintegrating and conventional tablets indicates that the mean absorption time (MAT) from these tablets is approximately 60 and 90 min, respectively. This difference in MAT between the two tablets may be caused by the difference in the sum of the mean dissolution time (MDT) and the mean disintegration time (MDIT) of these tablets. Rapidly disintegrating tablets allow rapid absorption of the drug compared with conventional tablets. PMID- 11217115 TI - An efficient synthesis of N-tert-butoxycarbonyl-O-cyclohexyl-L-tyrosine. AB - A facile and efficient synthesis of N-tert-butoxycarbonyl-O-cyclohexyl-L-tyrosine [Boc-Tyr(Chx)-OH] is described. Boc-Tyr-OH was treated with NaH in dimethylformamide and then with 3-bromocyclohexene to give N-Boc-O-(cyclohex-2 enyl)-L-tyrosine [Boc-Tyr(Che)-OH] in 70% yield. Hydrogenation of Boc-Tyr(Che)-OH over PtO2 afforded Boc-Tyr(Chx)-OH in almost quantitative yield. The highest yield was achieved when a side product in the synthesis of Boc-Tyr-OH, Boc Tyr(Boc)-OH, was not removed, because it was also converted to Boc-Tyr(Che)-OH without any additional manipulations. The new synthetic method described here is convenient for practical use, and would facilitate the widespread use of the Chx group for the hydroxy-protection of Tyr. PMID- 11217116 TI - Caffeic acid phenethyl ester (CAPE): synthesis and X-ray crystallographic analysis. AB - The structure of caffeic acid phenethyl ester [2-propenoic acid, 3-(3,4 dihydroxyphenyl)-, 2-phenethyl ester] (I), C17H16O4 x 1/2C6H6, synthesized by base-catalyzed alkylation of caffeic acid salt with beta-bromoethylbenzene in HMPA (hexamethylphosphoramide) and recrystallized from benzene, was confirmed by single crystal X-ray diffraction. The crystals are triclinic, space group P1, Z=2, unit cell dimension a=5.8129 (9) A, b=11.122 (2) A, c=13.226 (2) A, alpha=97.080 (3) degrees, beta=101.467 (3) degrees, gamma=95.405 (3) degrees , V=825.4 (2) A3, Dcalc=1.301 g/cm3, F(000)=342. The packing of the molecule is stabilized by intermolecular O1H...O4 (2.69 A) and O1...HO2 (2.82 A) hydrogen bonds. PMID- 11217117 TI - Latifolosides I and J, two new triterpenoid saponins from the bark of Ilex latifolia. AB - Two new triterpenoid saponins, latifoloside I (1), 3-O-alpha-L-rhamnopyranosyl-(1 ->2)-beta-D-glucopyranosyl 3beta,21alpha,28-trihydroxy-urs-12-ene 21-O-beta-D glucopyranoside; latifoloside J (2), 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D glucopyranosyl-3beta,21alpha-dihydroxy-ursolic acid 21-O-beta-D-glucopyranoside, along with two known compounds, latifoloside C (3) and latifoloside E (4), were isolated from the bark of Ilex latifolia THUNB. Structure assignments were established on the basis of spectroscopic data and chemical evidence. PMID- 11217118 TI - Vibsane-type diterpenes from Taiwanese Viburnum odoratissimum. AB - Two new eleven-membered and three new seven-membered vibsane-type diterpenes, named vibsanin L (1) and 14-hydroxyvibsanin F (2), and vibsanin I (3), 14R*,15 epoxyvibsanin C (4) and 14S*,15-epoxyvibsanin C (5) respectively, have been isolated from Viburnum odoratissimum collected in Taiwan. Their structures have been elucidated by spectroscopic analyses and comparison of Nuclear magnetic resonance method (NMR) data with those of the previously reported vibsane-type diterpenes. High performance liquid chromatography (HPLC) analyses indicated that the methanol extract of V. odoratissimum collected in Taiwan contained no neovibsanines, characteristic chemicals occurring in V. awabuki. PMID- 11217119 TI - Triterpene glycosides from the cultures of Phytolacca americana. AB - A new triterpene glycoside I was isolated together with the five known triterpene glycosides 2-6 from the cultures of Phytolacca americana. The structure of 1 was elucidated by analysis of spectroscopic data and comparison of its NMR data with those of 2-7 and chemical degradation. PMID- 11217120 TI - [Sentinel node: a revolution in breast cancer surgery?]. PMID- 11217121 TI - [Congential thrombocytic hemorrhagic dystrophy]. PMID- 11217122 TI - [Nail pathology]. PMID- 11217123 TI - [Fungal and bacterial nail infections]. AB - Fungal and bacterial infections are very common causes of nail deformity. The majority of fungal nail infections are caused by dermatophytes. Dermatophytosis result from a human contamination. A dermatophyte is always a pathogenic agent. Very effective drugs are available to treat dermatophyte nail infections. Yeasts of the genus Candida, notably C. albicans are the second most common cause of nail infection. The infections of nails due to Candida and bacteria are related with Candida sp and bacteria which are common commensals of the gastrointestinal tract, vagina or skin. Except C. albicans which is always a pathogen of skin, the other species of Candida and the bacteria could be a commensal of the skin, a colonizer of a dermatological disease or a true pathogen of nail. It is important to consider these different situations. More rarely, environmental moulds, most often known as saprophytic agents, can affect nails. They do not respond to conventional antifungal drugs. So, their diagnosis do not suffer any error. In order to evaluate properly the patient with possible fungal or bacterial infection of nails and also to choice an accurate therapy, the laboratory confirmation is essential. Clinical diagnosis is not sufficient to distinguish an infection of nails from a dermatological disease (psoriasis, traumatism) and to identify the responsible agent. PMID- 11217124 TI - [Nail localization of dermatoses]. AB - The nail unit may reflect a dermatological disease by its own. Actually, its involvement may account for the existence of a skin disease that never showed before (i.e. lichen planus). But since the nail apparatus has a limited repertoire of clinical expressions (hyperkeratosis, onycholysis, paronychia...), the diagnosis may be sometimes difficult even for the most trained physician. Nail involvement may be however an additional clue in the diagnosis of an atypical skin disease. In that case, it might help in the final correct diagnosis provided that the physician did not forget that clinical examination of the nails is part of a dermatological examination. PMID- 11217126 TI - [Nail tumors]. AB - The presenting sign associated with the tumours of the nail unit may involve: the colouration of the nail plate and/or the subungual tissue; the contour of the nail and the volume of the distal phalanx; the integrity of the nail (partial destruction or nail disappearance); abnormalities in the periungual tissues. The key for the early diagnosis of a nail tumour is a high index of suspicion of any non healing or recurrent condition in the area. Non-invasive studies such as X ray or MRI may be followed by the need of exploratory nail plate removal and adequate biopsy. PMID- 11217125 TI - [Nail manifestations of systemic diseases]. AB - General diseases-associated nail disorders may be classified into 5 types according to their clinical impact. Type I refers to nail disorders considered as peculiar features among the various symptoms of general disease such as peri ungueal vascular dilatation, onycholysis, Beau lines, opaque nails or melanonychia. Type II refers to nail disorders with a strong clinical value such as Terry's nails, Muerhrcke's lines or koilonychia. Type III refers to nails disorders presenting as significant syndromes of several diseases such as yellow nail syndrome of subungueal splinter haemorrhages, and type IV to specific disorders considered as true keys for diagnosis such as digital hippocratism, Bazex's acrokeratosis, Koenen's tumor, or nail hypoplasia. In type V are included drug-induced nails disorders especially after chemiotherapy or antiretroviral therapy. PMID- 11217127 TI - [Pigmented lesions of the nail apparatus]. AB - Linear pigmentation of the nail apparatus most reflects longitudinal melanonychia. It results either from simple activation of matrical melanocytes induced by various factors or from benign (lentigo or naevus) or malignant (melanoma) melanocyte hyperplasia. Hematomas and some fungal infections can falsely resemble linear pigmentation. Non-linear pigmented lesions of the nail bed are most often subungual hematoma or infections (fungal, or pyocyanic superfection of a loosened or separated nail). Opening the nail bed directs the diagnosis. A possible tumoral cause should be kept in mind, especially melanoma, or carcinoma. PMID- 11217128 TI - [Mechanical nail pathology]. AB - Nails are submitted to a lot of trauma in the everyday life; their response to these traumatisms is various and they show themselves in misleading clinical manifestations leading often to misdiagnosis such onychomycosis or nail pathology of another origin. As for toenails dystrophies, repeated microtraumatisms in the shoes are the main cause and these dystrophies often reveal biomechanical disorders. As for fingernails, except the occupational pathology which is not related in this paper, nails dystrophies are particularly self-inflicted due to an obsessional-compulsive disorder. We are describing here the different nails dystrophies of mechanical aetiology, the different original factors and their mechanisms, as well as signs leading to the diagnosis. PMID- 11217129 TI - [Nail pathology in children]. AB - In children the nail has physiologic characteristics that imply specific abnormalities. The most common dermatological localisation in psoriasis in the child; it is seen as trachyonychia, pitting, and occasionally pachyonychia. Ingrowth of the large toenail is a common problem, whether due to congenital hypertrophy of the lateral nail folds of the hallux in the newborn, to congenital malalignment of the nail of the big toe, or to a juvenile ingrown nail. Many other nail disorders are observed in the child: parakeratosis pustulosa, nail lichen, lichen striatus, melanonychia, dermatophyte onychomycosis, candida infection, herpes.... Aside from warts, tumours are rare. PMID- 11217131 TI - [Vaccinations. Immunological and microbiological bases, indications, contra indications, adverse effects, efficacy (schedule and mandatory character of excluded vaccinations]. PMID- 11217130 TI - [Cosmetology and brittle nails]. AB - The knowledge of manicure techniques and nail cosmetics compositions are a prerequisite to the understanding of their potential side effects. The brittle nail syndrome is a common problem that roughly affect 20% of women. We will review the etiologic hypothesis, describe the various presentations, and suggest a treatment for this perplexing problem. PMID- 11217132 TI - [Hospitalization requested by a third party and mandatory hospitalization, guardianship, trusteeship and legal protection]. PMID- 11217133 TI - [Bronchial epidermoid cancers and adenocarcinomas. Epidemiology, pathology, etiology, diagnosis, evolution, treatment]. PMID- 11217134 TI - [Extrauterine pregnancy]. PMID- 11217135 TI - [Respiratory distress in the newborn]. PMID- 11217136 TI - The JIM interview. Francois M. Abboud, MD. PMID- 11217137 TI - The future of clinical research: the role of genomics, informatics, and evidence based medicine. PMID- 11217138 TI - Perspectives on vascular biology and diabetes. PMID- 11217139 TI - Events at the vascular wall: the molecular basis of inflammation. PMID- 11217140 TI - Hepatic lipase as a focal point for the development and treatment of coronary artery disease. AB - Recent epidemiological evidence suggests that although lowering low-density lipoprotein (LDL) cholesterol is important in decreasing cardiovascular disease morbidity and mortality, it accounts only for part of the coronary artery disease (CAD) improvement with lipid-lowering therapy. In the last decade, it has become evident that the atherogenicity of LDL particles is associated not only with their plasma levels, but also with their size and density. The presence of small, dense LDL particles is associated with a three fold increase in CAD risk. Hepatic lipase (HL), a key enzyme in the formation of small, dense LDL particles, modulates their phospholipid and triglyceride contents. The higher the HL activity, the smaller, denser, and more atherogenic the resulting lipoprotein particle. It is, therefore, plausible to hypothesize that at least part of the CAD benefits observed in the recent CAD-prevention pharmacological trials, which are not accounted for by the decrease in LDL-C (LDL-cholesterol), might be explained by a pharmacological effect on LDL size and density, possibly mediated by changes in hepatic lipase activity. By studying patients with dyslipidemia and CAD, we have been able to provide strong evidence that regression of coronary atherosclerosis results from at least two independent effects of lipid-lowering therapy on lipoprotein metabolism: the well known one that leads to changes in LDL-C and apo B levels, and a new pathway of HL-mediated improvement in LDL buoyancy. Finally, HL activity and LDL density appear to be significantly affected by the presence of a common C-->T substitution at position -514 with respect to the transcription start site of the HL gene, raising the possibility that the -514 C-->T polymorphism may significantly contribute to differences in individual CAD response to lipid-lowering treatment, as seen in the recent major primary and secondary CAD-prevention clinical trials. PMID- 11217141 TI - Central role of the adipocyte in the metabolic syndrome. AB - Insulin resistance is associated with a plethora of chronic illnesses, including Type 2 diabetes, dyslipidemia, clotting dysfunction, and colon cancer. The relationship between obesity and insulin resistance is well established, and an increase in obesity in Western countries is implicated in increased incidence of diabetes and other diseases. Central, or visceral, adiposity has been particularly associated with insulin resistance; however, the mechanisms responsible for this association are unclear. Our laboratory has been studying the physiological mechanisms relating visceral adiposity and insulin resistance. Moderate fat feeding of the dog yields a model reminiscent of the metabolic syndrome, including visceral adiposity, hyperinsulinemia, and insulin resistance. We propose that insulin resistance of the liver derives from a relative increase in the delivery of free fatty acids (FFA) from the omental fat depot to the liver (via the portal vein). Increased delivery results from 1) more stored lipids in omental depot, 2) severe insulin resistance of the central fat depot, and 3) possible regulation of visceral lipolysis by the central nervous system. The significance of portal FFA delivery results from the importance of FFA in the control of liver glucose production. Insulin regulates liver glucose output primarily via control of adipocyte lipolysis. Thus, because FFA regulate the liver, it is expected that visceral adiposity will enhance delivery of FFA to the liver and make the liver relatively insulin resistant. It is of interest how the intact organism compensates for insulin resistance secondary to visceral fat deposition. While part of the compensation is enhanced B-cell sensitivity to glucose, an equally important component is reduced liver insulin clearance, which allows for a greater fraction of B-cell insulin secretion to bypass liver degradation, to enter the systemic circulation, and to result in hyperinsulinemic compensation. The signal(s) resulting in B-cell up-regulation and reduced liver insulin clearance with visceral adiposity is (are) unknown, but it appears that the glucagon-like peptide (GLP-1) hormone plays an important role. The integrated response of the organism to central adiposity is complex, involving several organs and tissue beds. An investigation into the integrated response may help to explain the features of the metabolic syndrome. PMID- 11217142 TI - Relationship of lipoprotein(a) to variables of coagulation in hypertensive subjects. AB - BACKGROUND: Coagulation factors are independent predictors of cardiovascular damage in the general population. The purpose of this study was to investigate the relationships between general cardiovascular risk factors, lipoprotein(a) (Lp(a)), and some hemostatic variables, and to characterize the isoforms of apolipoprotein(a) (apo(a)) in hypertensive subjects. METHODS: Plasma lipids, apolipoproteins, Lp(a), apo(a) isoforms, fibrinogen, and parameters that directly reflect the coagulation activation were measured in 389 untreated essential hypertensive patients recruited at a hypertension clinic. Hypertensive patients were compared with 323 normotensive controls. RESULTS: In normotensive subjects, Lp(a) concentrations were significantly correlated with fibrinogen (r = 0.138; P < 0.02) but not D-dimer (r = 0.074; not significant). In hypertensive subjects, log Lp(a) concentrations were significantly correlated with age (r = 0.127; P < 0.02), apo-B (r = 0.128; P < 0.02), plasma fibrinogen (r = 0.193; P < 0.001), and fibrin D-dimer (r = 0.200; P < 0.001) levels, but not with body mass index, blood pressure, cholesterol, triglycerides, apo-AI, prothrombin fragment 1 + 2, and antithrombin III. The relationship of Lp(a) with fibrinogen (male: r = 0.198, P < 0.002; female: r = 0.177, P < 0.01) and D-dimer (male: r = 0.211, P < 0.002; female: r = 0.188, P < 0.01) was significant in both sexes, whereas the relationship of Lp(a) with age and apo-B was found only in males. Multivariate analysis showed that both fibrinogen and D-dimer were independently related with Lp(a). Elevated fibrinogen, D-dimer, and Lp(a) levels were significantly and independently associated with clinical evidence of atherosclerotic disease. Apo(a) phenotypes were analyzed to investigate the genetic background of the relationships between Lp(a) and coagulation parameters. In both hypertensive and normotensive subjects, Lp(a) levels were inversely correlated with apo(a) isoform protein size, whereas fibrinogen and D-dimer concentrations were comparable in patients with apo(a) isoforms of different size. CONCLUSIONS: The relationship between Lp(a) and clotting variables is significantly stronger in hypertensive than in normotensive subjects, providing a compelling argument for accelerated progression of atherothrombosis in these patients. PMID- 11217143 TI - PPAR-gamma effects on the vasculature. PMID- 11217144 TI - Beneficial intervention of experimental colitis by passive cigarette smoking through the modulation of cytokines in rats. AB - BACKGROUND: Epidemiologic observations have indicated that cigarette smoking decreases the risk of ulcerative colitis, but the modes of action remain anonymous. The present study aimed to investigate the beneficial effects of passive cigarette smoking using an animal colitis model. We hypothesized that the underlying mechanisms may involve immunoregulation of cytokines. METHODS: Experimental colitis was induced in rats by enema administration of 2,4 dinitrobenzene sulfonic acid (DNBS). Passive cigarette smoking by rats was performed for 1 hour once daily, from 3 days before DNBS enema until they were sacrificed on day 8. Other groups of DNBS-treated rats received therapeutic treatment of cyclosporin A or pentoxifylline, a tumor necrosis factor (TNF)-alpha inhibitor. Macroscopic and histologic damage were graded, and the colonic levels of different cytokines and the levels/activities of parameters related to neutrophil activation were also measured. RESULTS: DNBS-induced colonic damage was improved in passive-cigarette-smoking rats. This was accompanied by attenuation of the elevated colonic myeloperoxidase and inducible nitric oxide synthase activities and leukotriene B4 level. Likewise, the augmentation in colonic levels of TNF-alpha, interleukin (IL)-1 beta, and IL-6 in colitis rats was also alleviated by passive cigarette smoking. In contrast, the deprivation of colonic IL-10 during colitis was preserved in cigarette-smoking rats. These effects were similarly accomplished by pentoxifylline and, to some degree, by cyclosporin A. CONCLUSIONS: The results support the idea that the beneficial effects of passive cigarette smoking in experimental colitis involved immunoregulation of cytokines in colonic tissues. PMID- 11217145 TI - Circadian phase resetting in older people by ocular bright light exposure. AB - BACKGROUND: Aging is associated with frequent complaints about earlier bedtimes and waketimes. These changes in sleep timing are associated with an earlier timing of multiple endogenous rhythms, including core body temperature (CBT) and plasma melatonin, driven by the circadian pacemaker. One possible cause of the age-related shift of endogenous circadian rhythms and the timing of sleep relative to clock time is a change in the phase-shifting capacity of the circadian pacemaker in response to the environmental light-dark cycle, the principal synchronizer of the human circadian system. METHODS: We studied the response of the circadian system of 24 older men and women and 23 young men to scheduled exposure to ocular bright light stimuli. Light stimuli were 5 hours in duration, administered for 3 consecutive days at an illuminance of approximately 10,000 lux. Light stimuli were scheduled 1.5 or 3.5 hours after the CBT nadir to induce shifts of endogenous circadian pacemaker to an earlier hour (phase advances) or were scheduled 1.5 hours before the CBT nadir to induce shifts to a later hour (phase delays). The rhythms of CBT and plasma melatonin assessed under constant conditions served as markers of circadian phase. RESULTS: Bright light stimuli elicited robust responses of the circadian timing system in older people; both phase advances and phase delays were induced. The magnitude of the phase delays did not differ significantly between older and younger individuals, but the phase advances were significantly attenuated in older people. CONCLUSIONS: The attenuated response to light stimuli that induce phase advances does not explain the advanced phase of the circadian pacemaker in older people. The maintained responsiveness of the circadian pacemaker to light implies that scheduled bright light exposure can be used to treat circadian phase disturbances in older people. PMID- 11217146 TI - Superoxide dismutase SOD1, encoded on chromosome 21, but not SOD2 is overexpressed in brains of patients with Down syndrome. AB - BACKGROUND: The antioxidant enzyme Cu/Zn-superoxide dismutase-1 (SOD1) gene is localized to chromosome 21q22.1 and catalyzes the dismutation of superoxide anions to hydrogen peroxide, which may lead to the increased production of active oxygen species in Down Syndrome (DS), trisomy 21. Although a number of studies have addressed this question, proposing the overexpression hypothesis, no specific protein-chemical data on SOD protein levels in the brains of patients with DS are available. METHODS: We therefore determined the protein SOD-1 and SOD 2 levels in the brains of controls (n = 9) and adult patients with DS (n = 9) and Alzheimer disease (AD; n = 9). Two-dimensional electrophoresis followed by matrix assisted laser desorption/ionization-mass spectroscopy detection and identification was used for the analyses. RESULTS: We found significantly increased SOD-1 levels in DS temporal, parietal, and occipital cortex, whereas SOD-1 was decreased in the AD temporal cortex and SOD-2 was comparable between all groups. CONCLUSIONS: Increased SOD-1 levels in patients with DS may reflect the overexpression by the trisomic state, as a response to the oxidative stress, as has been proposed in DS by several authors. However, it well may be that glial proliferation, which is markedly increased in DS brain, may underlie the increased brain levels of this ubiquitous protein. The decrease of SOD1 in the temporal cortex of patients with AD may reflect an antiapoptotic mechanism or simply cell loss in the brain. PMID- 11217147 TI - Primate mammary gland insulin-like growth factor system: cellular localization and regulation by sex steroids. AB - BACKGROUND: Insulin-like growth factor 1 (IGF1) plays a critical role in estrogen induced uterine proliferation, but it is unclear whether this estromedin function occurs in other estrogen-sensitive tissues such as the mammary gland. To elucidate this possibility, we investigated the cellular localization and hormonal regulation of mRNAs for IGF1 and 2, their cognate receptors (IGF1R, IGF2R), and IGF binding proteins 2-5 (BPs 2-5) in the rhesus monkey mammary gland. METHODS: Ovariectomized monkeys were treated with placebo, estradiol (E2), and E2 plus progesterone (E2/P4) for 3 days, after which mammary tissue was harvested for in situ hybridization and immunohistochemical analyses. RESULTS: IGF1 and IGF2 mRNA levels were significantly increased and BP2 mRNA decreased by E2 and by E2/P4 treatment. IGF1R mRNA was increased by combined E2/P treatment but not by E2 alone. BP5 mRNA was decreased by E2/P4. No differences in IGF2R, BP3, and BP4 mRNA levels were detected in any treatment group. Mammary IGF1 and IGF2 mRNA levels were both positively correlated with local epithelial proliferation, assessed by immunodetection of the proliferation-specific antigen, Ki67.IGF1 and IGF1R expression were negatively correlated with local programmed cell death, as assessed by the in situ TUNEL method. In contrast, BP2 expression was negatively correlated with epithelial proliferation and positively correlated with programmed cell death. IGF2R, BP3, BP4, and BP5 levels were not significantly correlated with either proliferation or death. CONCLUSIONS: Thus, E2-induced proliferation is associated with upregulation of both IGF1 and IGF2 expression and downregulation of BP2 expression. These data suggest that the local mammary IGF system is involved in sex steroid-induced mammary epithelial cell hyperplasia. PMID- 11217148 TI - Adenosine and hemodialysis in humans. AB - BACKGROUND: Infections and hypotension are serious complications that develop during hemodialysis (HD) treatment. Adenosine (ADO), a strong hypotensive and immunosuppressive agent, may participate in these two HD complications, because high concentrations of ADO metabolites are found in dialyzed human plasma. ADO, which is released by endothelial cells, is quickly transformed into inosine (INO) by plasmatic ADO deaminase (ADA) and mononuclear cell ADO deaminase (MCADA). In plasma, the degradation of ADO into INO and its uptake by red blood cells (RBC) are both very rapid, resulting in the short half-life of ADO in blood. METHODS: Using liquid chromatography, we evaluated ADO and INO plasma concentrations before and after HD session. RESULTS: Before the HD session, ADO and INO plasma concentrations were higher in hemodialyzed patients than in controls and in peritoneally dialyzed patients. At the end of the HD session, ADO plasma concentration was increased. ADO plasma concentration for the undialyzed patients was in the same range as that of the controls. Before HD, ADA activity was higher in hemodialyzed patients (559 +/- 349 IU) than in controls (219 +/- 48 IU), and the activity rose during the session (665 +/- 135 IU). ADA activity in the undialyzed patients (222 +/- 80 IU) was in the same range as that of the controls (219 +/- 48 IU). Before the HD session, the MCADA activity (247 +/- 144 IU) was lower than in controls (624 +/- 99 IU). HD did not modify ADO RBC uptake. ADO inhibited mononuclear cell proliferation and interferon-gamma production in humans. Finally, as much as 50 microM INO does not inhibit ADO uptake by RBC and does not modify ADA and MCADA activities. CONCLUSIONS: These data indicate that chronic HD inhibited MCADA activity and increased ADO plasma concentration. Both high ADO plasma concentration and low MCADA activity may be involved in dialysis induced immune system failure and thereby favor infectious diseases. PMID- 11217149 TI - Cigarette smoke and asbestos activate poly-ADP-ribose polymerase in alveolar epithelial cells. AB - BACKGROUND: Cigarette smoke augments asbestos-induced bronchogenic carcinoma in a synergistic manner by mechanisms that are not established. One important mechanism may involve alveolar epithelial cell (AEC) injury resulting from oxidant-induced DNA damage that subsequently activates poly (ADP-ribose) polymerase (PARP), an enzyme involved in DNA repair that can deplete cellular energy stores. We previously showed that whole aqueous cigarette smoke extracts (CSE) augment amosite asbestos-induced DNA damage and cytotoxicity to cultured AEC in part by generating iron-induced free radicals. We hypothesized that CSE increase asbestos-induced AEC injury by triggering PARP activation resulting from DNA damage caused by iron-induced free radicals. METHODS: Aqueous CSE were prepared fresh on the day of each experiment. PARP activity in WI-26 (a type I like cell line) and A549 (a type II-like cell line) cells was assessed by the uptake of labeled NAD over 4 hours and confirmed on the basis of the reduction of PARP levels in the presence of a PARP inhibitor, 3-aminobenzamide (3-ABA). Cell survival was assessed by trypan blue dye exclusion. RESULTS: Hydrogen peroxide (H2O2; 1-250 microM), CSE (0.4-10 vol%), and amosite asbestos (5-250 micrograms/cm2) each caused PARP activation in WI-26 and A549 cells. The combination of asbestos (5 micrograms/cm2) and CSE (0.04-10%) induced WI-26 and A549 cell PARP activation without evidence of synergism. 3-ABA significantly attenuated WI-26 and A549 cell PARP activity and cell death after exposure to H2O2, CSE, and asbestos. Phytic acid, an iron chelator, catalase, and superoxide dismutase each decreased WI-26 cell PARP activation caused by asbestos and CSE. CONCLUSIONS: CSE and asbestos induced PARP activation in cultured AEC in a nonsynergistic manner. These data provide further support that asbestos and cigarette smoke are genotoxic to relevant lung target cells and that iron-induced free radicals in part cause these effects. PMID- 11217150 TI - Productivity of medical research in Switzerland. AB - BACKGROUND: Little evidence exists about what contributes to successful medical research, an increasingly important issue in an era of limited research budgets. This study examined predictors of productivity of Swiss medical research. METHODS: Principal investigators of clinical research projects funded by the Swiss National Science Foundation between 1990 and 1994 were surveyed by mail. They provided information about the research question, whether changes were made to the protocol and why, their assessment of the importance of results for science and for public health, and additional funding of the project. The amount of the grant and the project priority score were obtained from the Foundation. Indicators of scientific productivity were the number of peer-reviewed articles and the summed impact factor per grant. RESULTS: The size of the grant predicted scientific output (number of articles and summed impact factor), but the marginal return decreased with the total sum awarded. The award of a continuation grant by the same agency and additional funding from other sources were also positively linked with productivity. In addition, the initial priority rating of the project by the funding agency's scientific committee and the assessment of scientific importance of the results by the principal investigator were also independently associated with productivity. Finally, modifications of the initial research plan in response to new scientific opportunities were linked with greater productivity, whereas modifications induced by technical or other difficulties were associated with lower productivity. CONCLUSIONS: Productivity in medical research, measured by peer-reviewed articles produced, requires adequate resources and ability to respond to new scientific challenges, and it can be anticipated by peer-review. PMID- 11217152 TI - The debriefing "controversy" and crisis intervention: a review of lexical and substantive issues. AB - Despite a long and rich history as a specialty within applied mental health, crisis intervention has, within recent years, been the target of criticism. Singled out for specific criticism has been the intervention referred to as "debriefing." Some authors have not only challenged its effectiveness but have raised the specter that it may cause significant harm. While superficially such arguments appear to have merit, closer scrutiny reveals an antiquated interpretation of even the most fundamental of terms and concepts inextricably intertwined with research based upon applications contrary to the most recent principles, prescriptions, and protocols regarding clinical use. A review of research based upon more extant formulations reveals many crisis intervention practices, including the Critical Incident Stress Debriefing model of "debriefing" and the Critical Incident Stress Management (CISM) model of crisis intervention to be highly clinically effective, indeed. This paper will review the terms and concepts which serve as the foundation of the field of crisis intervention, while subsequently reviewing key research investigations addressing its efficacy. It may be that outcome research directed toward assessing the effectiveness of crisis intervention can prosper from following trails blazed by psychotherapy researchers. The parallels seem striking. It may be that outcome research in crisis intervention (and "debriefing") needs to now focus upon "who" does crisis intervention, to "whom," and in "what specific situations," so as to maximize outcome associated with this clinically effective tool [International Journal of Emergency Mental Health, 2000, 2(4), 211-225]. PMID- 11217151 TI - Insulin receptor antibodies inhibit insulin uptake by the liver: in vivo 123I insulin scintigraphic scanning and in vitro characterization in autoimmune hypoglycemia. AB - BACKGROUND: Insulin receptor antibodies can induce severe hypoglycemia or insulin resistance in rare autoimmune syndromes. In vitro properties of these antibodies occasionally explain the clinical features of the syndrome, but direct evidence of their in vivo activity is poor. We studied a 58-year-old male with rheumatoid arthritis who presented with hypoglycemic coma. METHODS AND RESULTS: Antibodies were detected by inhibition of 125I-insulin binding to human insulin receptor-3T3 cells by the patient's serum. By immunofluorescence, they were immunoglobulin G of all four subclasses, immunoprecipitated insulin receptors from biotin-labeled cells, and triggered phosphorylation of the beta subunit of the insulin receptor. Insulin binding on the patient's red blood cells was markedly reduced. A biodistribution study after intravenous 123I-Tyr A14 insulin showed a marked inhibition of tracer uptake by the liver, reaching 10% of the injected dose (controls, mean +/- SD, 21.1 +/- 1.7%; n = 10). Time activity curves generated on the liver and on the heart were parallel, with a T1/2 of 11.5 minutes for both, suggesting that no specific uptake occurred in the liver, where tracer activity represented only the blood pool. Clearance of insulin from the blood was indeed slower than in controls and mainly occurred through the kidneys. Analysis of plasma 123I-insulin immunoreactivity and trichloroacetic acid precipitate showed that insulin degradation did not occur as in normal controls. CONCLUSIONS: In this patient with hypoglycemic syndrome, insulin receptor antibodies with in vitro insulin-like activity are capable of blocking in vivo the access of insulin to the liver receptor compartment, as directly demonstrated by the markedly altered biodistribution of intravenously injected 123I-insulin. PMID- 11217153 TI - In defense of defending what may not be so obvious in the CISD/CISM efficacy debates. PMID- 11217155 TI - Past violence and substance use disorder and subsequent violence towards others: six year analysis of the Assaulted Staff Action Program (ASAP). AB - Recent research has begun to document evidence of associations between past violence toward others, untreated personal victimization, and substance use disorder and later acts of violence toward others. This appears true for many types of individuals, including psychiatric patients who have been victims of violence. This six-year retrospective study sought to evaluate these possible associations in assaultive psychiatric patients. Data were gathered in the context of the Assaulted Staff Action Program (ASAP), a crisis intervention program for staff victims of patient assault. Both histories of violence (violence toward others and/or personal victimization) and substance use disorder in assaultive psychiatric patients were individually and jointly examined and found to be associated with subsequent assaults by these patients. Increased levels of both past violence toward others, personal victimization, and substance use disorder were associated with the largest increased frequency of subsequent assault. The implications and possible links to emergency mental health services are discussed [International Journal of Emergency Mental Health, 2(4), 241-247]. PMID- 11217154 TI - Predictors of secondary trauma in sexual assault trauma counselors. AB - This study evaluated psychological distress, secondary trauma intensity, and specific components of secondary trauma in 89 sexual assault trauma counselors (SATC). Results indicated that some SATC were experiencing secondary trauma based on measures of psychological distress and PTSD-like symptoms. The study also examined whether personal trauma history, greater counseling experience, emergency room work as primary client contact type, counseling satisfaction levels, and demographic variables significantly predicted self-reported psychological distress and PTSD-like symptoms. Results supported the hypothesis that personal trauma history and younger age significantly predicted self reported psychological distress. Results also supported hypotheses that personal trauma history, younger counselor age, and lower counseling satisfaction levels significantly predicted higher levels of secondary trauma intensity. Contrary to prediction, exposure to trauma survivors, emergency room work as primary client contact type, and education did not significantly predict psychological distress or secondary trauma intensity. Findings were robust even when SATC currently in psychotherapy or taking medication were conservatively excluded in follow-up analyses. Research and training implications are discussed [International Journal of Emergency Mental Health, 2000, 2(4), 229-240). PMID- 11217156 TI - The critical incident stress debriefing process for the Los Angeles County Fire Department: automatic and effective. AB - Los Angeles County Fire Department has one of the oldest Critical Incident Stress Management (CISM) programs in the country. One core component for the LACoFD has been the Critical Incident Stress Debriefing (CISD). Two important questions for the emergency managers are: 1) Do individuals find a significant difference in symptom reduction for events that were debriefed? 2) Does helpfulness of a debriefing for a specific individual correlate with recommending the process for others? A Department-wide evaluative survey was conducted in 1996 to determine the satisfaction and effectiveness of the debriefing program. Individuals reported a significant difference in the speed of symptom reduction for incidents that were debriefed versus incidents that were not debriefed. The majority of individuals would recommend the debriefing process to others regardless of whether they personally found the process helpful or not. Based on this, the recommendations are to continue the debriefing process for specific events and to make the process mandatory; furthermore, it is recommended that the term "mandatory" be changed to "automatic." By using the term "automatic," debriefings become standard operating procedures. By doing so, a method to protect the psychological welfare of emergency personnel becomes as automatic as putting on safety protection equipment [International Journal of Emergency Mental Health, 2000, 2(4), 249-257]. PMID- 11217157 TI - Posttraumatic stress symptomatology in patients with automatic implantable cardioverter defibrillators: nature and intervention. AB - With the advent of DSM-IV, medical illness may be considered a traumatic event. Yet there is evidence that a lifesaving intervention, the automatic implantable cardioverter defibrillator (AICD) may be associated with PTSD, as well. Crisis intervention is reviewed as a possible model to assist AICD patients in their adjustment to AICD discharge and its associated distress [International Journal of Emergency Mental Health, 2000, 2(4), 259-263]. PMID- 11217158 TI - Disaster management and the Goteborg Fire of 1998: when first responders are blamed. AB - On Thursday, the 29th of October, 1998, Goteburg, Sweden experienced one of its greatest fire related catastrophes. Sixty-three people lost their lives in a Goteburg discotheque. This paper describes the events surrounding the fire, its effects upon firefighters and the city of Goteborg, and the emergency mental health activities implemented to support fire and rescue personnel. Of particular importance were the effects experienced by fire and rescue personnel as they became targets for community grief and anger. This paper discusses the lessons learned from organizational and personnel points of view [International Journal of Emergency Mental Health, 2000, 2(4), 267-273]. PMID- 11217159 TI - [Treatment of infants with acute diarrhea in Hungary]. AB - In the treatment of infants with acute diarrhoea complicated by mild to moderate dehydration, there is a great importance of rapid rehydration over 3-4 hours with oral rehydration solution containing 60 mmol/l sodium and then the rapid reintroduction of normal diet or breast feeding which should be continued all the time if possible. The pharmacological treatment of diarrhoea is not justified. In the present study which was part of a European multicentre survey using questionnaires the authors analysed how the recommendation of European Society of Pediatric Gastroenterology, Hepatology and Nutrition are followed in Hungary. It was evaluated 131 returned questionnaires, 80 of primary care and 51 of hospital based pediatricians. The overwhelming majority of pediatricians (92%) recommended the oral rehydration at the beginning of treatment. The four fifth of them use the ORS with recommended composition. Only 31% of them use rapid oral rehydration over 3-4 hours. Merely 10% of them suggest the early reintroduction of normal feeding after the oral rehydration, while more than half of the respondent pediatricians (52%) think that temporarily the use of lactose free formula is justified. It is a very favourable fact that 84% of doctors recommend the continuation of breast feeding. Some kind of drugs for the treatment of diarrhoea is suggested by 15% of repliers. On the base of results it is obvious that the guidelines for the treatment of acute diarrhoea in infancy is complied only partially in Hungary and the reintroduction of normal feeding is delayed. PMID- 11217160 TI - [The role of HDL in the prevention of cardiovascular events]. AB - The Framingham and other epidemiological studies have shown HDL and triglyceride to be inversely correlated. An independent relationship between HDL cholesterol and CAD was observed in other studies and also suggested by interventional trials. Decreased HDL-C and mildly elevated LDL-C are common in patients with coronary artery disease. Identification of receptors involved in the metabolism of HDL has been the subject of intensive research. The HDL particle may be recognized by different receptors in various tissues. Niacin and fibrate have a remarkable effect on the reduction of triglyceride and elevation of HDL, while their LDL lowering effect is moderate. Statins are effective and safe drugs for CHD, and exert beneficial effects across the lipoprotein profile. Therefore, the effects of statins on HDL-C may contribute to reductions in coronary events. PMID- 11217161 TI - [Physical illness and suicidal behavior. Review of results at the Pecs Center of the WHO/EURO Multicenter Study of Parasuicide]. AB - The authors examined the relation of physical illness, suicidal behaviour and help-seeking patterns among suicide attempters within the framework of the WHO/EURO Multicentre Study on Parasuicide. Until now 700 monitored suicidal events have been collected; 101 structured interviews and 50 follow-up cases have been conducted in this three years period. Physical and mental problems proved to be very frequent among suicide attempters and many of them took somatic and psychiatric drugs. It was shown that patients with acute or chronic physical and mental illness more often had been in contact with GPs. Authors pointed out that in addition to mental problems the somatic diseases are significant risk factors in suicidal behaviour. In many cases these factors were not recognised and thus patients could not get help. Authors emphasised the importance of training GPs, since complex diagnostic and therapeutic approach is essential to prevent suicide. PMID- 11217162 TI - [Combination, transition and degrees of severity of various syndromes]. AB - Nowadays it is difficult to recognise and separate the various syndromes. The geneticists and the morphologists often change the classification of syndromes. The problem may be caused by a new case of a known syndrome, when new symptoms are described among the known ones. Then it is not sure, if a new syndrome discovered or it is a more complicated variation of an already known syndrome. To emphasise and exemplify the difficulties of syndrome identification 5 patients are presented and analysed: on with anadysplasia, two with cleidocranial dysplasia and a sibling pair with Larsen syndrome. It is concluded that no new syndrome could be described, and in a similar context, the definition of several new syndromes is not justified. The classification of syndromes based on bone disorders must be modified in order to fit the Genetic Classification easier and more clearly. PMID- 11217163 TI - [Olanzapine and pregnancy]. AB - The appearance of psychosis during pregnancy means a challenge for clinicians, either untreated psychiatric disorders or pharmacological treatment of pregnant psychotic females increase risk of complications. Controlled clinical trials can't be evaluated because of ethical considerations, so case reports have higher scientific values than in other clinical issues. The authors inform about a delivery of a young psychotic female, who was treated with olanzapine (atypical antipsychotic) after the 25th weeks of her pregnancy. A healthy newborn was born in the observed case, the Apgar score was 7 at the first minute and 9 at fifth minute. PMID- 11217164 TI - [Contribution to the subject of scientific qualifications and leadership potential in medicine]. PMID- 11217165 TI - [Continuing medical education in Hungary]. PMID- 11217166 TI - Police reporting and professional help seeking for child crime victims: a review. AB - Most crimes with child victims are not reported to police, nor do child victims access other professional victim services, despite evidence that these yield positive outcomes. This article develops a conceptual framework about the barriers to such access: (a) the reluctance to define the crime episodes or their consequences as serious, criminal, harmful, or warranting intervention; (b) the extra authorities, including parents and schools, who mediate between victims and police or services; (c) developmental issues, such as concerns about autonomy; (d) attitudinal and emotional obstacles; and (e) time and expense factors. This article suggests the need for initiatives to stimulate reporting and help seeking, such as more publicity about the seriousness of juvenile victimization, more justice-system involvement with schools, more child and family friendly police services, and an emphasis on attractive outcomes such as justice and empowerment. PMID- 11217167 TI - Abusive early child rearing and early childhood aggression. AB - Childhood aggression is significant for children, their families, and the society because aggressive children often become violent adolescents. This article examines the relationship between maltreatment and early childhood aggression. Data are from a longitudinal study of maltreated and nonmaltreated children assessed as preschoolers and again at school age. The dependent variable is the child's teacher's rating of aggression at school age. The independent variables are from preschool and school age observations of the mother-child interaction and the mother's report of physical discipline practices. Using structural equation modeling, harshness of interaction at preschool age but not school age and severity of physical discipline at school age but not preschool age, relate to aggression at school age. Results suggest a difference in the developmental stage at which different features of harsh child rearing exert their influence. Strategies for intervening to prevent the development of childhood aggression are suggested. PMID- 11217168 TI - Evolution of a classification scale: medical evaluation of suspected child sexual abuse. AB - This article presents a revision of a system for classifying examination findings, laboratory findings, and children's statements and behaviors as to their possible relationship to sexual abuse. The revisions are based on published research studies and current recommendations from the American Academy of Pediatrics Committee on Child Abuse and Neglect, and the American Professional Society on the Abuse of Children. Part 1 of the classification system lists genital and anal findings that can be considered normal or nonrelated to abuse, nonspecific for abuse, concerning for abuse, and clear evidence of blunt force or penetrating trauma. Under Part 2, the overall classification of the likelihood of abuse is broken into four categories: no evidence of abuse, possible abuse, probable abuse, and definite evidence of abuse or penetrating trauma. Cautions in the use of the classification system, as well as controversies concerning a few medical findings, are discussed. PMID- 11217169 TI - Child Sexual Behavior Inventory: normative, psychiatric, and sexual abuse comparisons. AB - A normative sample of 1,114 children was contrasted with a sample of 620 sexually abused children and 577 psychiatric outpatients on the Child Sexual Behavior Inventory (CSBI), a 38-item behavior checklist assessing sexual behavior in children 2 to 12 years old. The CSBI total score and each individual item differed significantly between the three groups after controlling for age, sex, maternal education, and family income. Sexually abused children exhibited a greater frequency of sexual behaviors than either the normative or psychiatric outpatient samples. Test-retest reliability and interitem correlation were satisfactory. Sexual behavior problems were related to other generic behavior problems. This contributed to the reduced discrimination between psychiatric outpatients and sexually abused children when compared to the normative/sexually abused discrimination. PMID- 11217170 TI - Pediatric anogenital exam: a theory-driven exploration of anticipatory appraisals and affects. AB - Smith and Lazarus's 1990 and 1993 theory of cognition-emotion associations guided this exploration of individuals' pre-exam experiences. The study also tested the model's integrity during a stressful event and examined its downward extension to children. A total of 47 girls ages 8 to 14 (M = 11.57, SD = 2.14) and 109 adult guardians of female patients (all ages) completed a brief questionnaire about their pre-exam thoughts and feelings. The majority of participants viewed the impending exam as important and desirable, reported optimism and confidence in their ability to cope or adjust, and described mild-moderate anxiety as well as moderate-high hope/gladness. The majority of adults also reported relatively high levels of sadness. Data supported the model's cognition-emotion associations. This theory-driven research offers a richer understanding of children who may have been sexually abused and their supportive adult guardians and encourages more positive and realistic expectations for these individuals. PMID- 11217171 TI - The relationship between interview characteristics and accuracy of recall in young children: do individual differences matter? AB - The relationship between interview characteristics and accuracy of recall in young children, as mediated by child characteristics, was examined. The interview characteristics included preinterview instructions and level of questioning. Fifty-six children ranging from ages 3 to 6 years participated in a Circus Day event and were interviewed 10 days later. Following either instructions or filler questions, children were questioned about the event. Results indicated that based on several individual difference factors, young children varied significantly in the accuracy of their interviews and their ability to resist misleading questions. However, individual differences did not mediate children's ability to benefit from different question types or preinterview instructions. As a whole, children provided limited information to the most open-ended questions and more correct information to highly structured questions. In contrast to the research with older children, younger children did not benefit from preinterview instructions. Suggestions for future research and implications for investigative interviews in the field of child abuse are discussed. PMID- 11217172 TI - 'Giveback' legislation restores funding for Medicare, Medicaid programs. PMID- 11217173 TI - Final rule on health information privacy issued. PMID- 11217174 TI - Neurotoxins licensed as treatment for neck neuromuscular disorder. PMID- 11217175 TI - Certification now required for Texas pharmacy technicians. PMID- 11217176 TI - Development and implementation of a tobacco consultation program for managed care pharmacists. PMID- 11217177 TI - Rituximab: an innovative therapy for non-Hodgkin's lymphoma. AB - The epidemiology, etiology, classification, and treatment of non-Hodgkin's lymphoma (NHL) are reviewed, and rituximab, a newly available therapy, is discussed. NHL comprises a group of lymphoproliferative disorders the frequency of which continues to rise. Although many classification systems exist for identifying specific histological subtypes, NHL is generally divided into indolent (low-grade) and aggressive (intermediate- and high-grade) forms. Low grade NHL is characterized by a slowly progressive, continually relapsing course, with eventual transformation to a more rapidly progressive form that is usually fatal. Several options are available for the management of indolent NHL; none is curative. Rituximab, a human-mouse monoclonal antibody that targets the CD20 antigen expressed in over 90% of B-cell NHLs, provides an alternative to conventional chemotherapy that is relatively safe and effective. In a Phase III trial involving 166 patients with relapsed or refractory low-grade B-cell NHL, rituximab produced an overall response of 48%, with 20 of 80 responders still in remission more than 36 months after treatment. Study results in patients with bulky disease and those requiring retreatment have also been encouraging. Most adverse effects associated with rituximab are mild to moderate. Infusion-related reactions occur more commonly during initial infusions and in patients with evidence of increased tumor burden but can be effectively managed with premedication, supportive care, and adjusted infusion rates. Hematologic effects are generally mild and transient, and adverse immune responses are rare. Rituximab is an alternative to conventional chemotherapy for the treatment of relapsed or refractory low-grade or follicular CD20-positive B-cell NHL. PMID- 11217179 TI - Stability of carmustine in polyvinyl chloride bags and polyethylene-lined trilayer plastic containers. PMID- 11217178 TI - Citywide pharmaceutical preparation for bioterrorism. AB - One community's efforts to become pharmaceutically prepared for an attack with biological agents is described. In response to recent bioterrorist activities, including a local scare in 1999 involving anthrax, the pharmacy department at Deaconess Medical Center in Spokane, Washington, was asked to develop a plan for bioterrorism preparedness. A literature search was conducted, and resources, such as the Centers for Disease Control and Prevention, were contacted. For each biological agent, information was compiled about symptom onset, treatment, postexposure prophylaxis, patient isolation precautions, and the availability of antidotes at local hospitals. A procedure was developed for obtaining antidotes that might not be available or stocked in sufficient quantities. After being reviewed by appropriate authorities, the information was presented to area hospitals and trauma centers, drug wholesalers, hospital risk-management personnel, and emergency management personnel. In May 2000 dozens of emergency and medical personnel attended a day-long program on domestic preparedness. Citywide cooperation was obtained on how to respond to a mass exposure to a bioterrorism agent. The job of a pharmacist during a bioterrorism strike is to rapidly disseminate antidotes and information, provide dosage and vaccination schedules for both treatment and prophylaxis, and counsel patients. Medical facilities in Spokane have cooperated to make the community more prepared for a bioterrorist attack. PMID- 11217180 TI - Reliability of an instrument for evaluating antimicrobial appropriateness in hospitalized patients. PMID- 11217181 TI - Use of a multidisciplinary continuous-quality-improvement process to investigate succinylcholine treatment failures. PMID- 11217182 TI - Evaluation of antimicrobial surgical prophylaxis with multiattribute utility theory. PMID- 11217183 TI - Gender differences in the associations of self esteem, stress and social support with functional health status among older adults with heart disease. AB - This study explored and compared the role of self esteem, stress and social support in maintenance or improvement in physical and psychosocial functioning over 12 months in older men and women with cardiovascular disease. Data from 502 adults over 60 years of age showed that self esteem and stress were both significantly associated with functioning when demographic and clinical factors were controlled. Men were significantly more likely than women to maintain or improve in functioning. Self esteem, stress, compliance with medication regimens, and marital status were significantly associated with maintenance or improvement of functioning among women. Only age and stress were significantly associated with maintenance or improvement in functioning among men. Findings indicated that: (1) stress and self esteem were stronger predictors of functioning, especially among women, than demographic and clinical factors; and (2) women in the highest quartile of the self esteem distribution were approximately five times as likely to maintain or improve their functioning as women in the lowest quartile. PMID- 11217184 TI - Anticipatory caregiving anxiety among older women and men. AB - This study, based on a sample of 221 older women and men, explores factors associated with anticipatory caregiving anxiety using a scale developed by Cicirelli (1988). Results show that even the anticipation of providing care evokes anxiety. We find that women have higher levels of anxiety than men, individuals who have served as caregivers have higher levels of anxiety than individuals who have never provided care to family members, and that individuals who are in better health and have more income have lower levels of anxiety than those with less health or income. Implications for services to support caregivers and long-term care reform are discussed. PMID- 11217185 TI - A chronology of the study of older women's health: data, discoveries, and future directions. AB - Women have been traditionally ignored in health and medical research. Some reasons for this mentality include a fear of harming a woman's reproductive ability, fear that variations in the menstrual cycle could confound results, fear that a woman's body could not withstand the rigors of clinical research, and an assumption that male and female body chemistry is similar. Thankfully, these fears and assumptions are being challenged and several major data-bases, designed specifically to study women's health, have emerged. The purpose of this paper is to: (1) characterize the major longitudinal studies on women's health, (2) summarize the major discoveries from these studies that are relevant to older women, and (3) pose several future directions for research throughout the paper. PMID- 11217186 TI - Importance of fatalism in understanding mammography screening in rural elderly women. AB - This study examined the relationship between demographic factors and other correlates of fatalism, and assessed the impact of fatalistic beliefs on the participation in breast cancer screening in rural women. The subjects were 220 women aged 50 and over recruited from 6 large rural counties in South Carolina. Data were collected using a demographic questionnaire and the revised Powe Fatalism Inventory. Results show significant associations between fatalism and increased age (p = 0.005), race (p = 0.0001), doctor recommendation (p = .0034) and decreased educational level (p = 0.001). Fatalism was associated with noncompliance with mammography screening in univariate analysis among African American women (OR = .362; 95% CI: 1.11, 11.8). After adjusting for possible confounders (age, education, and doctor recommendation), fatalism was not significantly associated with noncompliance with screening. These results illustrate age, race, and education may be important predictors of fatalism and that fatalism may be one barrier that has previously gone unmeasured and unchallenged in understanding screening behavior in older women. PMID- 11217187 TI - Aging, chronic illness and self-concept: a study of women with osteoporosis. AB - The coalescence of aging and chronic illness may alter the relationships between the meanings of aging and chronic illness and the self-concept. Using Rosenberg's conceptualization of self-concept (1979), a qualitative study was designed and data collected from twenty-eight women with osteoporosis. Three types of self concepts emerged from the data: the confident self, the contradictory self and the disparaged self. A description of these types is presented highlighting the reciprocal relationship among meanings of aging and chronic illness and self concept and including discussion of the strategies used to enhance, protect and maintain self-concept despite changes brought on by aging and chronic illness. PMID- 11217188 TI - [Precancerous lesions of the uterine cervix in cameroonian women. Cytological and epidemiological aspects of 946 cases]. AB - OBJECTIVE: The aim of this study was to present the cytological and epidemiological aspects of precancerous lesions of the uterine cervix of women living in the two first cameroonian cities (Yaounde and Doubla). MATERIAL AND METHODS: The material was made of pap smears registrar of the Yaounde Central Hospital pathological laboratory and the reports of cervical cancer screening from Douala and Yaounde within a period of five years (1st January 1994 to 31st December 1998). We recruited all cases showing a precancerous lesion of the uterine cervix. For each case, we noted: the type of lesion, the age of the patient, the age at the first sexual intercourse, the age at the first delivery, the number of pregnancies, the parity, the marital status, the socioeconomical class. RESULTS: From a total of 13524 pap smears done, 946 (7%) have shown precancerous lesions. 70% of these were high grade while 30% were low grade. These lesions were observed at all age from the range of 11 to 15 years. All women showing these lesions had had sexual intercourse. 30% of these lesions were noted among women who have had their first sexual intercourses between 10 and 15 years. 40% were observed among women who have had their first sexual intercourses between 16 and 18 years. 66% among women who have had their first delivery between 13 and 21 years. 92% are observed among women who have had more than five pregnancies, more than five parities; 54% among women who are married and 76% among bachelors and widows; 64% among women with low socioeconomical status; 9% among women with high socioeconomical status. CONCLUSION: Many cameroonian women are prone to cervical cancer. PMID- 11217189 TI - [Evaluation of cost of laparoscopic surgery in gynecology]. AB - The objective of this work was to evaluate hospital and postoperative costs associated with gynecologic laparoscopic surgery for benign pathologies. Hospital costs were broken down into several categories: operating room, postoperative hospitalization, pharmacy, surgical instruments, sterilization of reused equipment, food and laundry, indirect costs. The mean total costs for the hospitalization time were 8547,2 francs. Medical charges in recovery time were calculated with the help of the Social Security. These charges represented less than 5% of the total cost associated with the procedure. PMID- 11217190 TI - [Breast cancer and its psychological approach: family, others, chance and...me]. AB - Since several years already, the scientific literature evoked the psycho oncological perspective in the psychotherapeutic treatment of the patient suffering of a malignant mammary pathology. The objective of this article is to insist on some characteristics of personality inherent to the individual that suffers of a malignant mammary pathology. Comparing three groups of women (malignant mammary pathology--n = 51, benign mammary pathology--n = 71 and a group controls--n = 30), a set of questionnaires relating to locus of control and to the close circle--family and couple--has been managed. Results indicate that the woman suffering of a breast cancer is less "intern", consider that her health depends on factor "luck" and wish less cohesion and therefore more of distance within her couple and her family. PMID- 11217191 TI - [Pregnancy outcome and the status of the newborn infant after ICSI at La Conception Hospital in Marseille]. AB - OBJECTIVE: To evaluate obstetric outcome of pregnancies and pediatric follow-up of children born after ICSI procedure. MATERIAL AND METHOD: Prospective study from october 1994 to September 1998 in medical assisted procreations center in La Conception hospital in Marseilles. Three hundred forty-two couples undergoing ICSI procedures. INTERVENTIONS: analysis of pregnancy rates, prematurity rates, obstetric outcome and frequency of congenital malformations. RESULTS: One hundred seventy-eight pregnancies have been obtained with 111 children. Multiple pregnancy rate arise 29.7%. The average term at birth in the singleton pregnancies (38.7 weeks) is higher than in the twins (35.7 weeks). The prematurity rate of delivery before 35 weeks of gestation is about 9.6%. Seven of 111 neonates was born with a congenital malformation, no cardiovascular one. One of boys presents a bilateral cryptorchidism with severe bilateral hypotrophy. CONCLUSIONS: Our results are similar with those of others teams. Congenital malformation rates is near rates reported in others studies. However, no bilateral cryptorchidism with bilateral severe hypotrophy has been yet reported in literature. PMID- 11217193 TI - [Mastodynia]. PMID- 11217192 TI - [From pathological diagnosis to ovulation induction. The case of ovarian insufficiency]. AB - The incidence of premature ovarian failure (POF) is around 1 to 3%. This pathology occurs in young women, who often wish to become pregnant. Theoretically, two mechanisms could be involved: initial follicle depletion and follicle dysfunction. However, in some cases, mixed mechanisms are involved. Initially, PFO was considered irreversible. In fact, signs of intermittent ovarian function in normal karyotypically women have been described, but predicting the probability of spontaneous remission in a specific woman is impossible. Therefore, various treatments for ovulation induction have been proposed to these patients. Most of the pregnancies occur after hormone replacement therapy. The action of this treatment is unclear and the cause-and effect relation has not been proven by prospective, randomized studies. The benefit of suppressing endogen gonadotropins by GnRH agonists is not proven either. Estrogen supplementation and high-dose gonadotropin ovarian stimulation protocols have been proposed. Even so, this therapy cannot be recommended because of the lack of controlled studies. Finally, numerous case reports have described the return of ovarian function after using immunosuppressive therapies. The lack of particular criteria for the diagnosis of autoimmune mechanisms have lead to treat heterogeneous groups of patients. No randomized controlled studies with immunologic monitorage have been performed that could establish the success of this therapy. Therefore, in order to find effective treatments, basic pathophysiologic mechanisms must be better understood. For those women who want to become pregnant, the lack of prospective, randomized studies cannot lead to formal conclusions. Depending on the patients' age and history, it appears reasonable to attempt a corrective therapy based on defined etiology, before entering in a donor oocyte program. PMID- 11217194 TI - [Pelvimetry by scanography]. PMID- 11217195 TI - [Serum markers in breast cancer and colorectal cancer (1997)]. PMID- 11217196 TI - [Fibroma: surgical myomectomy or embolization or GnRH analogs? Intramural and sub serous fibroma: start with medical treatment!]. PMID- 11217197 TI - [Fibroma: surgical myomectomy or embolization or GnRH analogs? Embolization of uterine fibroma: a new treatment]. PMID- 11217198 TI - [Fibroma: surgical myomectomy or embolization or GnRH analogs? Does myomectomy by laparoscopy have a justifiable place in the therapeutic strategy today?]. PMID- 11217199 TI - [The end of a French paradox]. PMID- 11217200 TI - [First World War and the explosion of venereal disease morbidity. IV. Prophylaxis]. PMID- 11217201 TI - [Breast cancer and pregnancy. Review of the literature]. AB - INTRODUCTION: The pregnancy-associated breast cancer seems to have become increasingly common with a high frequency of advanced breast cancer with axillary node metastases and so associated with poor prognosis. MATERIALS AND METHODS: This review examines the diagnosis, prognosis, and management of cancer during pregnancy; both in terms of the cancer's effect on the pregnancy, and the pregnancy's effect on the cancer. RESULTS: Diagnostic procedures (breast sonography) and excisional biopsies are necessary to reduce the delay of several months or more after discovery of a mass and before treatment. No histological difference, between patients with pregnancy-associated breast cancer and patients with non-pregnancy-associated breast cancer, was diagnosed. CONCLUSION: The treatment is linked to the effects of adjuvant therapy on the fetus. PMID- 11217203 TI - Post-transplant immune serological markers may be predictive of chronic rejection. PMID- 11217202 TI - Pharmacological surrogates of allograft outcome. AB - Because virtually all of the currently available oral immunosuppressive agents show significant inter- and/or intrapatient variability, drug doses do not predict patient exposure, which is the critical parameter of efficacy versus toxicity. Therefore, at least for the critical-dose baseline immunosuppressive agents CsA and tacrolimus, all transplant centers use some sort of therapeutic drug monitoring. However, for CsA, Cminss values show a poor correlation with exposure and therefore are of limited use. Reliable therapeutic drug monitoring demands some measure of CsA absorption profiles with or without an estimate of clearance rates. The suggested methods include full AUC, limited sampling AUC, and a single 2- or 3-hour post-dose blood concentration. For tacrolimus, Cminss displays a reasonable correlation with systemic drug exposure as measured by AUC, however, there is little correlation between Cminss and clinical events within recommended therapeutic ranges. Sirolimus, which has been recently approved for use in kidney transplant recipients by the Food and Drug Administration in 2 or 5 mg doses, also shows the behavior of a critical-dose drug and that therapeutic monitoring using trough levels correlate strongly with drug exposure and the occurrence of adverse events. However, there is no approved automated assay and thus LC estimates must be utilized to estimate exposure. Pharmacodynamic drug monitoring opportunities are available for calcineurin inhibitors, MMF and sirolimus, but none is currently available for clinical use; however, the field of transplant pharmacodynamics is progressing rapidly. In the coming decade it is likely that an array of pharmacodynamic tools will be developed to complement the available pharmacokinetic information and lead to the development of models that predict optimal concentrations at the target sites in order to maximize immunosuppression and minimize toxic effects. PMID- 11217204 TI - Post-transplant glomerular filtration rate as a marker for long-term outcome. PMID- 11217205 TI - Post-transplantation histology as surrogate marker for long-term kidney allograft outcome. PMID- 11217206 TI - Subclinical rejection--a potential surrogate marker for chronic rejection--may be diagnosed by protocol biopsy or urine spectroscopy. AB - Our studies of protocol biopsy studies have shown that normal allograft histology can not be assumed by crude tests of renal function such as the serum creatinine concentration, and that there is a high prevalence of subclinical rejection in the first 6 months post-transplant (7, 13-17). The apparent ability of urine MR and IR spectra to reliably identify patients with normal allograft histology, if confirmed in a larger database, will preclude the need for a protocol biopsy in approximately 20-50% of patients. Conversely, finding urine MR or IR spectra characteristic of subclinical rejection would provide the opportunity for early treatment. The clear separation between patients with normal histology from those with subclinical rejection can be attributed to the use of the whole urine spectrum to develop the classifiers. Additional advantages of using MR or IR spectra of urine as a diagnostic tool compared to the biopsy include simplicity (i.e. no processing is required), low cost, rapid turnaround (i.e. < 15 minutes/sample), and, particularly, low risk, thus allowing for repetitive sampling. The ability to non-invasively diagnose acute inflammation in the kidney would be of great assistance in the post-transplant monitoring of renal transplant patients. Indeed, by following subclinical inflammation as detected in the MR/IR spectra it will be possible to tailor the intensity of the immunosuppression to the inflammatory status of the graft, thus minimising the risks of both insufficient and excessive immunosuppression. Furthermore, by following subclinical inflammation, as detected in the MR/IR spectra, it will be possible to test the hypothesis that subclinical rejection (i.e. persistence of its MR/IR spectral classifier) is a surrogate marker for the development of chronic rejection. PMID- 11217207 TI - Surrogate biomarkers of long-term outcome after kidney transplantation. PMID- 11217208 TI - Cellular immunology markers postransplantation predictive of long-term graft outcome. PMID- 11217209 TI - Cytokine profiles as marker for graft vascular disease after clinical heart transplantation. PMID- 11217210 TI - Surrogate markers of chronic allograft nephropathy. PMID- 11217211 TI - Colour cues for oviposition behaviour in Toxorhynchites moctezuma and Toxorhynchites amboinensis mosquitoes. AB - Gravid female Toxorhynchites moctezuma (Dyar and Knab) and Toxorhynchites amboinensis (Doleschall) were offered the choice of coloured (spray-painted) containers for oviposition in laboratory trials. Both species oviposited preferentially into black containers rather than into white, red, yellow, green, or blue containers. Black containers also acted as oviposition stimulants of Tx. moctezuma females, and black and red containers for Tx. amboinensis females. Absorption spectra were measured for the paints used, with red and black paints absorbing more light across most of the visible spectrum than the other colours. PMID- 11217212 TI - Differences in response to temperature and density between two strains of the mosquito, Culex pipiens molestus forskal. AB - Two strains of Culex pipiens molestus of different geographical origin were reared for more than five years under the same laboratory conditions in order to study to what extent the reactions of these strains to constant temperature and density become similar. Lower temperature and higher densities caused not only the prolongation of developmental time of preimaginal stages and increasing mortality of larvae and pupae in both strains but also the extension of the rate between the first and last emerging imago in both sexes of both strains. Absolute time spent in the preimaginal stage was also influenced by genetic factors. Both strains displayed different values, although both strains were for reared in the laboratory under identical conditions. PMID- 11217213 TI - Species composition and seasonal dynamics of mosquitoes in the Belek region of Turkey. AB - The species composition and seasonal population dynamics of mosquitoes trapped in the Belek Region of Turkey are described. Eight traps (four New Jersey light traps and four CO2 baited traps) were activated weekly at four different sampling sites (wooded area, open field, village, and road edge). Between May and December, 1997, 4,542 specimens representing seven species (Culex pipiens, Culex tritaeniorhynchus, Aedes caspius, Aedes cretinus, Aedes dorsalis, Aedes vexans, and Culiseta annulata) were collected. The most abundant species was Cx. pipiens (26.7% of total catch) followed by Cx. tritaeniorhynchus (23.8%), Ae. caspius (23.4%), Ae. cretinus (10.7%), Ae. dorsalis (8.7%), Cs. annulata (6.2%), and Ae. vexans (0.1%). This is the first record of Ae. cretinus in the area since 1984. The species was captured throughout the study period, although it was most abundant in late summer. Culex tritaeniorhynchus reached its highest density in August, while Cx. pipiens was found in high numbers throughout most of the study period. PMID- 11217214 TI - New records of the blacklegged tick, Ixodes scapularis (Acari: Ixodidae) in Minnesota. AB - The Minnesota distribution of the blacklegged tick, Ixodes scapularis, was studied during 1998 and 1999. The majority of tick collecting was done by grouse hunters, who sent in specimens collected during the fall of 1998 and 1999. I. scapularis specimens were received from 17 counties, including eight counties in northern and central Minnesota that previously had no reports of I. scapularis. This brings the number of Minnesota counties with reported populations of I. scapularis to 30, mostly in the east-central, central, and northern parts of the state. PMID- 11217215 TI - Landing periodicity of Aedes aegypti with implications for dengue transmission in Trinidad, West Indies. AB - The diel landing/biting periodicity of the Trinidad strain of Aedes aegypti (L.) was monitored using human-bait during January-August 1999. Hourly light intensities were measured both indoors and outdoors at both urban and rural sites. The periodicity of females was diurnal and nocturnal, with 90% arriving during daylight and twilight and 10% during the night. The pattern of landing was trimodal, with consistent peaks at 0700 h, 1100 h and 1700 h. The diel periodicities at indoor and outdoor urban sites were virtually identical. In contrast, the periodicities in rural areas differed, with no nocturnal activities being recorded at indoor and outdoor sites. At both urban and rural sites, larger numbers of adults were collected outside than inside houses. A significant correlation between light intensities and mosquito landing patterns was observed. The implications of the changing landing patterns of Ae. aegypti within urban areas are discussed in light of the epidemiology and control of dengue fever in Trinidad. PMID- 11217216 TI - A taxonomic review of the North American genus Orchopeas Jordan, 1933 (Siphonaptera: Ceratophyllidae: Ceratophyllinae). AB - The 20 named taxa assigned to the North American flea genus Orchopeas Jordan, 1933 are reviewed. Four of these are treated as junior synonyms and the fifth as a nomen dubium. These are: Orchopeas sexdentatus firemani Hubbard, 1955 = Orchopeas schisintus (Jordan, 1929); Orchopeas schisintus nevadensis (Jordan, 1929) = Orchopeas schisintus agilis (Rothschild, 1905); Orchopeas howardi bolivari Barrera, 1955 = Orchopeas howardi (Baker, 1895); Orchopeas howardi texensis Eads, 1950 = Orchopeas fulleri Traub, 1950 and Orchopeas labiatus (nomen dubium). Six taxa originally assigned as subspecies of Orchopeas sexdentatus are elevated to the rank of full species and distribution and host preferences of all 15 species are discussed. Illustrations of the diagnostic features of all the species are provided. PMID- 11217217 TI - Influence of nymphal Anax imperator (Odonata: Aeshnidae) on oviposition by the mosquito Culiseta longiareolata (Diptera: Culicidae) and community structure in temporary pools. AB - We assessed the overall (consumptive plus non-consumptive) and non-consumptive effects of nymphal Anax imperator (Aeshnidae: Odonata) on experimental pool communities by comparing three treatments: (1) control (no Anax); (2) free Anax (Anax was not constrained); and (3) caged Anax (Anax, enclosed within a cage, could not consume prey outside the cages, but could possibly influence them via perceived risk of predation). Fewer egg rafts of the mosquito Culiseta longiareolata were found in the free Anax treatment compared to the other two treatments. There was no statistically significant difference in the number of egg rafts between control and caged Anax pools. Thus, while Culiseta females apparently oviposit fewer egg rafts in the presence of unconstrained Anax, they did not respond to predation risk from the caged Anax. Larval Culiseta densities were drastically reduced by free Anax; there was nearly a 100% reduction in the number reaching metamorphosis (pupae) and a 100% reduction in emergence (pupal exuviae). There were no significant treatment effects on densities of crustaceans, Daphnia magna and Heterocypris sp., or on chironomid pupal exuviae. Ceratopogonid pupal abundance was higher in free Anax pools than in the other two treatments toward the end of the experiment. Free Anax caused a trophic cascade, presumably by strongly reducing the dominant periphyton grazer, Culiseta larvae; periphyton mass was greater in the free Anax treatment than in the control. However, there was no behavioral trophic cascade, i.e., no difference in periphyton abundance between the control and caged Anax treatment. PMID- 11217218 TI - Plasmodium vivax polymorphs and Plasmodium falciparum circumsporozoite proteins in Anopheles (Diptera: Culicidae) from Belize, Central America. AB - Eight species of Anopheles mosquitoes from indoor/outdoor human landing collections in Belize, Central America, were examined for human Plasmodium circumsporozoite protein (CSP) using an enzyme-linked immunosorbent assay (ELISA). A total of 14 of 9,104 females tested were positive from general surveys throughout Belize and three of 11,966 were positive from a longitudinal study in Caledonia, northern Belize. ELISA results, using pooled head-thorax preparations and species-specific monoclonal antibodies directed against the circumsporozoite proteins of Plasmodium falciparum and two Plasmodium vivax polymorphs (210 and VK247), found four species reactive: Anopheles vestitipennis (3 pools), Anopheles darlingi (2 pools), Anopheles albimanus (10 pools), and Anopheles gabaldoni (2 pools). The minimum field infection rates (MFIR) for combined Plasmodium species from the general survey were 0.282% for An. vestitipennis, 0.271% for An. darlingi, 0.126% for An. albimanus, and 0.395% for An. gabaldoni. MFIRs for combined Plasmodium species from the longitudinal study in the village of Caledonia were 0.018% for both An. vestitipennis and An. albimanus and 1.66% for An. gabaldoni. Positive CSP pools were collected from the Cayo, Corozal, Orange Walk, Stann Creek, and Toledo political districts. No CSP positive pools were detected from collections in the Belize District. The study provides valuable information on the spatial distribution and species type of Plasmodium positive mosquitoes. This information, in combination with other vector data, suggest that An. vestitipennis and An. darlingi are commonly involved in malaria transmission. Additionally, these species appear to be much more efficient vectors than An. albimanus in Belize. PMID- 11217220 TI - Influence of sanitary conditions on the field performance of chlorpyrifos-based baits against American cockroaches, Periplaneta americana (L.) (Dictyoptera: Blattidae). AB - The role of sanitation in performance of insecticidal bait stations containing 0.5% chlorpyrifos against the American cockroach, Periplaneta americana (L.), was investigated in residential premises. Test sites were chosen from three locations in Penang Island, Malaysia, and clustered according to their sanitary conditions. Results indicated that at 1-week post-treatment, houses with good sanitary conditions showed a significantly faster reduction (P > 0.05) in the number of cockroaches trapped (> 95%) than those with moderate and poor conditions. At 6 weeks post-treatment, all houses treated with insecticidal baits showed no significant difference in terms of reduction rate of cockroach numbers (P > 0.05), irrespective of sanitary condition. However, the bait performance in houses with poor sanitary conditions could not be sustained up to 12-week post treatment. PMID- 11217219 TI - The relationship between size and fecundity in Aedes albopictus. AB - Recent use of correlates of the intrinsic rate of increase and models to study population dynamics in mosquitoes has emphasized the need for species specific data on the relationship of morphological factors such as body size to life history parameters such as fecundity. Aedes albopictus is of concern because of its continued spread and population growth in the U.S. and the potential for virus transmission. We examined the relationships between pupal wet weight and adult female wing length and between female wing length and fecundity in the first gonotrophic cycle in U.S. strains of Ae. albopictus. There was a significant positive relationship between pupal wet weight and adult wing length. The relationship between wing length and fecundity was also significant and positive, but with lower correlation coefficients and higher variance indicating that other factors also affect fecundity. The regression coefficients for the fecundity-wing length equation did not differ between two strains of Ae. albopictus. PMID- 11217221 TI - Rodent ectoparasites from two locations in northwestern Florida. AB - From Feb.-Apr. 1999, 19 species of ectoparasitic arthropods (2 sucking lice, 4 fleas, 4 ticks, 2 mesostigmatid mites, 5 chiggers, 2 fur mites) were recovered from 106 rodents belonging to 5 species (cotton mouse, Peromyscus gossypinus, n = 64; cotton rat, Sigmodon hispidus, n = 23; eastern woodrat, Neotoma floridana, n = 9; golden mouse, Ochrotomys nuttalli, n = 9; eastern gray squirrel, Sciurus carolinensis, n = 1) at Tall Timbers Research Station, Leon County, Florida. During the same period, 13 species of ectoparasites (2 sucking lice, 1 flea, 3 ticks, 3 mesostigmatid mites, 2 chiggers, 2 fur mites) were recovered from 57 rodents belonging to 3 species (S. hispidus, n = 40; black rat, Rattus rattus, n = 16; S. carolinensis, n = 1) from Panama City, Bay County, Florida. Noteworthy ectoparasite records include Ixodes minor from both sites, which extends the known geographical range of this tick, and Stenoponia americana from Tall Timbers that represents the second documented Florida record of this flea. Potential tick vectors (Dermacentor variabilis and Ixodes scapularis) of zoonotic pathogens (Rickettsia rickettsii and Borrelia burgdorferi) were collected at both sites. On S. hispidus, fleas were more prevalent at Tall Timbers but sucking lice, chiggers, ticks, mesostigmatid and listrophorid mites all were more prevalent at the Panama City site. Arthropods recovered from arboreal nests (n = 3) of O. nuttalli at Tall Timbers included 3 species of ectoparasites (1 tick, 2 laelapid mites). PMID- 11217222 TI - Bacterial abundance in larval habitats of four species of Anopheles (Diptera: Culicidae) in Belize, Central America. AB - Numbers of free-living and attached bacteria were counted in surface waters from larval habitats of four species of Anopheles mosquitoes: Anopheles albimanus Wiedemann, An. darlingi Root, An. vestitipennis Dyar and Knab, and An. pseudopunctiopennis Theobald, using a direct count method and DAPI staining technique. Bacterial counts from larval habitats were compared to those from adjacent open water. Several additional variables such as total suspended solids (TSS), particulate organic carbon (POC), and dissolved organic carbon (DOC) were also recorded in order to establish possible relationships with bacterial characteristics. Our results showed that the waters from larval habitats were enriched with bacteria as well as POC and DOC compared to open water. The major component of all samples consisted of cocci, the proportion of rods was similar and there were significantly more attached rods in habitat samples than in open water samples. Anopheles vestitipennis habitats had the highest values of each of the categories of bacteria as well as of POC and DOC. PMID- 11217223 TI - Correlates of violent assault among young male primary care patients. AB - Correlates of violent assault (defined here as having been shot, stabbed, shot at, or beaten) were identified among young male primary care patients. Data were analyzed from a cohort of young men ages 17 to 29 during their initial visits to an urban primary care facility. Each underwent a clinical assessment, including a self-report health inventory and provider history. In multivariable analysis, history of incarceration (odds ratio [OR] = 6.29, 95 percent confidence interval [CI], 2.34-16.89), having children (OR = 3.06, 95 percent CI, 1.30-7.17), and a high school education or less (OR = 0.69, 95 percent CI, 0.50-0.96) were significantly associated with increased likelihood of violent assault. Patients reporting more serious traumatic experiences, such as incarceration, witnessing violence, or carrying a weapon, had the highest risk (OR = 9.91, 95 percent CI, 4.0-24.57). These findings may help primary care physicians identify young men at risk for violence and foster better interventions. PMID- 11217225 TI - Health data issues for Hispanics: implications for public health research. AB - The limited availability of Hispanic health data has hampered the development of targeted public health policies. Hispanics represent 11.5 percent of the population and are projected to become the largest minority group in the United States by the year 2010. This paper explores current issues in Hispanic health data collection, examines methodological concerns, and presents recommendations for future Hispanic public health data collection. Data are derived from statistical reports of the U.S. Bureau of the Census, National Center for Health Statistics, Bureau of Labor Statistics, and other empirical studies. Recommendations include: collecting both race and ethnic-specific data by Hispanic subgroup, designing appropriate data collection instruments and approaches, and selecting referent groups for comparison purposes. The authors conclude that the renewed national focus on health disparities among underserved populations requires an increased commitment to adequately identify Hispanic subgroups. PMID- 11217224 TI - Is variation in quality of mammographic services race linked? AB - The purpose of this investigation was to (1) determine whether there was variability in the quality of services offered in mammography facilities across Connecticut and (2) determine whether African American women were more likely than white women to receive mammograms in facilities that offered substandard services. Since most facilities do not routinely record information on race, this investigation represents a unique opportunity to address the question of race linked variation in the quality of screening mammography. Information on equipment, personnel, and record keeping in mammography facilities was used to construct indices that represented separate domains of quality: technical attributes, educational practices, and tracking of clients. While some variation in the quality of mammography services was found, there were no significant differences between the two race categories in the mean scores for each of three quality indices. Thus, variation in quality of screening mammographic services does not appear to be race linked. PMID- 11217226 TI - Consumer participation in health policy decisions: empowerment or puffery? AB - Many consumers in today's society have increased access to information about health and medical care through books, videotapes, audiotapes, the Internet, and television programming. However, consumers often are excluded from involvement in health policy decision making because it is believed that they do not have the necessary expertise. In this paper, the following will be discussed: (1) the historic role of consumer involvement in health policy decision making, (2) an overview of major barriers that consumers have encountered in health policy decision making, and (3) strategies for overcoming these barriers so that consumer empowerment can be enhanced when they serve on health policy panels. PMID- 11217227 TI - Community cancer control in a rural, underserved population: the Appalachian Leadership Initiative on Cancer Project. PMID- 11217228 TI - Health care utilization among homeless adults prior to death. AB - This study characterizes health care utilization prior to death in a group of 558 homeless adults in Boston. In the year before death, 27 percent of decedents had no outpatient visits, emergency department visits, or hospitalizations except those during which death occurred. However, 21 percent of homeless decedents had a health care contact within one month of death, and 21 percent had six or more outpatient visits in the year before death. Injection drug users and persons with HIV infection were more likely to have had contact with the health care system. This study concludes that homeless persons may be underusing health care services even when they are at high risk of death. Because a subset of homeless persons had extensive health care contacts prior to death, opportunities to prevent deaths may have been missed, and some deaths may not have been preventable through medical intervention. PMID- 11217229 TI - Utilizing patient satisfaction surveys to prepare for Medicaid managed care. AB - To prepare for Medicaid managed care, a community health center incorporated the business principle of continuous quality improvement, often used in the private sector to improve customer service, into its planning process. The initial endeavor was to create a patient satisfaction survey that was appropriate for the uniqueness of the community. The survey, taken monthly, resulted in both staff and patients making active improvements in the clinic environment. Staff showed more enthusiasm, and patients were more assertive in their attitudes toward the clinic. The empowerment of the patient to take ownership in the clinic will be coupled with the next step of the formalized plan, that of educating patients on the steps necessary to ensure that their Medicaid managed care facility will be the local community health center. PMID- 11217230 TI - Crossing the border for health care. AB - A survey was administered to adults attending a health fair in south Los Angeles County, approximately 140 miles from the U.S.-Mexico border. The survey revealed that 14 percent of respondents had crossed the border to seek medical care during the past year. Nearly 80 percent of respondents crossing the border for medical care were uninsured, while 70 percent reported the low cost of medical care obtained across the border as being the most common reason for seeking care there. Twenty-eight percent of respondents reported purchasing medication in Mexico, with antibiotics and pain medication being reported in highest frequency. Ninety percent of these respondents were uninsured. This study shows that the high cost of health care and lack of insurance compels the poor and uninsured to seek low-cost health care and medication in Mexico to meet their most urgent health care needs, despite the burden of cost and travel. PMID- 11217231 TI - Concentrated poverty and nursing home bed supply in Chicago. AB - This study explores whether poverty areas of Chicago have fewer nursing home beds and unique staffing patterns. Using 1990 census data and Illinois's 1994 Long Term Care Facility Survey, census tracts were compared by need for long-term care, bed supply, and nursing home characteristics. While facilities cluster on the north side, and the number of beds follow the elderly, the supply of beds per elderly is actually greater in tracts with high proportions of poverty, disability, and African American residents due, in part, to the predominance of larger facilities. Ironically, economic segregation may work together with Medicaid's policy of serving the poorest to increase the supply of beds to those who might otherwise remain unserved. Nursing homes in the poorest communities have high percentages of Medicaid residents, are larger, and employ fewer staff per resident; homes with a high Medicaid population are more likely to employ LPNs, which may reflect labor supply differences. PMID- 11217232 TI - A 5-year prospective study of Astra single tooth implants. AB - AIM: To evaluate the AstraTech Implant ST (Molndal, Sweden) for single tooth replacement clinically and radiographically after 5 years in function. SUBJECTS AND METHOD: Fifteen patients (age range 16 to 48) with missing maxillary anterior teeth (6 central incisors, 8 laterals, 1 bicuspid) had four 13 mm and eleven 15 mm single tooth implants provided. All patients were seen at 4- to 6-monthly intervals for oral hygiene maintenance. Periapical radiographs using Rinn holders and a long cone technique were taken at the crown insertion and after 1 year, 3 and 5 years. RESULTS: No implant losses were observed in 14 of the 15 patients available for evaluation. No abutment screw loosening or soft tissue problems were observed. At crown insertion the mean bone level was 0.46 +/- 0.55 to 0.48 +/- 0.56 mm apical to the top of the implant neck and there were no statistically significant changes in the radiographic bone level over the 5 years of the study (0.36 +/- 0.37 to 0.43 +/- 0.46 mm at year 5). One crown was recemented after 18 months in function and 1 crown was replaced because of a fracture to the porcelain incisal edge. CONCLUSION: The Astra Tech Implants ST were highly successful in single tooth replacement and bone levels during 5 years of function were stable. PMID- 11217233 TI - [Acute cell death of cultured rat hippocampal neurons due to mitochondrial disorders]. PMID- 11217235 TI - [Drug donations: help or problem?]. PMID- 11217234 TI - [How much tuberculosis do we want?]. PMID- 11217236 TI - [Recommendations for the control of cholesterolemia in Spain]. AB - A number of recommendations are provided regarding the detection, assessment and management in primary and secondary prevention, approaching hypercholesterolaemia from a multifactorial standpoint based on cardiovascular risk. Cardiovascular diseases are the leading cause of death in Spain. The major risks involved are coronary heart disease and cerebrovascular disease. The demographic, health related and social impact thereof will be increasing over the coming decades. Controlling hypercholesterolaemia, in conjunction with eradicating the smoking habit and controlling hypertension, diabetes, obesity and physical inactivity comprise one of the main strategies for preventing cardiovascular diseases. Breaking down the risk of individuals based on the major cardiovascular risk factors is essential, given that these factors condition the frequency with which these individuals must be monitored and the type and degree of treatment entailed. Based on this breakdown, the priorities have been set for taking steps to prevent cardiovascular disease. In primary prevention, the therapeutic objective in high-risk persons (20% risk or higher or those persons involving two or more risk factors) has been established as LDL-cholesterol < 130 mg/dl. In secondary prevention, drug treatment is indicated when LDL-cholesterol (130 mg/dl and the therapeutic objective is LDL-cholesterol < 100 mg/dl. Those patients having coronary heart disease must be included in secondary prevention programs that will ensure good, constant clinical and risk factor-related control. PMID- 11217237 TI - [Hepatitis B vaccination. Indications of the post-vaccine serologic test and booster doses]. AB - The standard anti-HBV vaccination elicits protective anti-HBs levels (above 10 UI/l) in most people. However, the effective duration of immunologic memory is not well-known. Consequently, the recommendations on the postvaccination follow up are not uniform: from vaccination with no follow-up blood test (anti-HBs levels) to regular follow-up blood tests for all vaccines. In unresponsive subjects a booster dose has been demonstrated to be effective. However, the optimal procedure for management depending anti-HBs levels has not been well established. Postvaccination antibody testing and regular testing for antibodies is recommended only to high-risk subjects, especially to health care workers and subjects with immunodeficiency. In these cases, the booster dose should be administered in nonresponders, and might include double doses. Unanimous consensus does not exist about to the appropriate timing for booster dose administration. PMID- 11217238 TI - [Efficiency in primary health care: a critical review of frontier measures]. AB - The object of this paper is to review applied research on primary care efficiency in Spain performed using parametric and nonparametric production and cost frontiers. A review of the most important bibliographic databases showed 12 applied papers that used frontier approach to measure primary care efficiency in Spain. The most part of these papers only used Data Envelopment Approach to measure technical efficiency scores. There is only one study that has employed a stochastic and nonparametric approach to obtain cost efficiency estimates. Activity measures such as number of visits are a usual measure of output and inefficiency sources are rarely analysed in this literature. Important methodological problems observed in this literature severely limit their practical utility. Future research should consider more accurate output measures, use available methods more appropriately, and shed light on the sources of inefficiency. PMID- 11217239 TI - [Legal framework and strategy of the tobacco industry in relation to tobacco advertising in Spain]. AB - Publicity is legally regulated in Spain, in order to avoid its misuse. Tobacco publicity is also under those regulation, having had the companies operating in this sector to adapt themselves through new strategies. In this work, the legal restrictions existing in Spain regarding publicity are analyzed, together with some of the strategies developed by tobacco companies in order to elude them. In this sense, and despite of the existing legal framework, it should be noticed that tobacco companies are cleverly taking advantage of the existence of legal loopholes in tobacco publicity to promote their products. PMID- 11217240 TI - [Distribution and trends of tuberculosis by age groups and municipalities in La Habana City, Cuba (1986-1998)]. AB - BACKGROUND: The province of Havana City, the capital and most densely populated city in Cuba, totals around 27% of the new cases of tuberculosis. This article is for the purpose of describing the distribution and trend of the tuberculosis cases rates from 1986 to 1998, by municipalities and age groups in this province. METHOD: A calculation was made of the rates and of the total percentage of deviation of these rates, in addition to the annual average deviation both throughout two time periods and between the two (1986-1993 and 1994-1998). The trends were calculated by simple linear regression. RESULTS: Throughout the 1986 1993 period, the case rate for this province underwent a 6% increase. Throughout the 1994-1998 period, it dropped by 7.3%. The three most densely-populated cities showed a higher rate increase. Of the 15 municipalities, only La Lisa showed a drop in the rates throughout the entire period in question. The rates by ages were similar throughout all of the municipalities, being higher for individuals > 65 years of age. Six tenths (0.6%) of the cases reported involved people under 15 years of age. The infantile tuberculosis rates were very low for the time period under analysis. CONCLUSIONS: The differences among the municipalities in question make it necessary for different measures to be taken to achieve a greater impact and repercussion in Cuba. The drop in the rates detected over the last three years is indicative of the epidemic being brought under control and the national tuberculosis control program being reinstated. PMID- 11217241 TI - [Anisakiasis in fresh fish sold in the north of Cordoba]. AB - BACKGROUND: Anisakiasis is a parasitic zoonosis caused by live larvae of the Anisakidae Family found located in the body cavities and in the muscular systems of osseous fish and cephalopod mollusks. Humons inadvertently ingest these larvae when eating raw or undercooked infested fish. Symptoms are characterized by gastrointestinal disorders. The purpose of this study is that of ascertaining the frequency of anisakid larvae parasite infestation in fresh fish marketed in northern section of the province of Cordoba. METHODS: Over a nine-month period, samples were taken of the species of sen fish sold to the greatest degree at all of the establishments in this sector. The parasite analysis was conducted at the Penarroya Public Health Laboratory by the dissection method. A total of 1,261 samples of 18 different species were analyzed. RESULTS: The total frequency of parasite infestation was 15.8%. The species in which the most parasites were found was the blue whiting (Micromesistius poutassou) showing a 42% parasite infestation rate, and Anisakidos larvae were also found in: hake (Merlucius merlucius) (27.5%), whiting (Merlucius sp.) (26%), mackerel (Scomber scombrus), greater forkbeard (Phycis blennoides) (6.2%), anchovy (Engraulis encrasicolus) (5.6%) and pouting (Trisopterus luscus) (5.5%) of the samples in which parasites were found. The monthly spread of the results reveals an increase in parasite infestation during the spring months, declining progressively up to the last months of the year. CONCLUSIONS: There is a significant degree of Anisakidos infestation in the species marketed in the northern section of the province of Cordoba. Nevertheless, the difficulty of detecting this parasite, the vague assessment of the degree of parasite infestation tolerable or unacceptable as set forth under regulations, the fact that some traditional dishes made from raw fish require fresh or refrigerated products and, lastly, the lack or complete lack of health education on the part of the population make it advisable for this emerging problem to be approached with greater rigor. PMID- 11217242 TI - [Outbreak of cryptosporidiosis in Guadarrama (Autonomous Community of Madrid)]. AB - BACKGROUND: In spring of 1998, an acute gastroenteritis outbreak, which mainly affected preschool children, took place in Guadarrama (Community of Madrid, Spain). METHODS: A descriptive and analytical (cases and controls) study of the outbreak was done. Stool samples of the cases were taken to microbiological investigation. The tap water getting system of the municipality was inspected and samples were collected to microbiological analysis. RESULTS: Twenty one children from 0 to 5 years-old had liquid diarrhea which lasted more than five days. A significant statistical association was found within tap water consumption and gastroenteritis [OR = 5.73 (1.18-43.30); p < 0.05]. It did not have association with other variables investigated. Cryptosporidium parvum (Cp) oocysts were detected in stool samples of eight cases. Deficiencies were observed in the tap water getting and treatment system of the municipality but no oocysts were found in the analysis of the water. CONCLUSIONS: The results of the epidemiological investigation support that the source of the gastroenteritis outbreak was tap water, likely contaminated with Cp. While this parasite was not detected in the analysis of the water, it is explainable for the difficulties which this technique involves. In our review similar descriptions of outbreaks have not been found in Spain, but it seems that this reports are not infrequent in neighbour countries. Therefore, Cp should be borne in mind in diagnostic and management of these situations. PMID- 11217243 TI - [Extent of law compliance and anti-smoking teaching at Spanish schools]. AB - OBJECTIVE: Knowing the degree of fulfillment of the anti tobacco legislation in Spanish schools and the influence that this has on the percentage of smoking pupils. MATERIAL AND METHODS: A survey was carried out among 3050 headmasters of Spanish schools, who were asked about different aspects of the fulfillment of the antitobacco laws in their schools and about the main characteristics of tobacco consumption in their centers. RESULTS: A 80.9% of the headmasters claim that the fulfillment of the legislation is demanded in their centers, and only a 64.9% of them have posters in theirs schools that warn people about smoking ban. Anti tobacco teachings are imparted in a 82.2% of the schools where laws is demanded and only in a 64.8% where is not demanded. The percentage of teachers who, smoke in the presence of the pupils is of a 5.9% in the schools where anti tobacco legislation is demanded and a 12.9% where is not demanded. In the schools where anti tobacco teachings are imparted, a 29% of the pupils have tried tobacco, opposite a 31% who have tried in the schools where these teachings are not imparted. CONCLUSIONS: The, headmasters of the schools, as people in charge of watching over the fulfillment of the anti tobacco legislation in theirs schools, must demand the fulfillment of this one, because this measure is effective in order to improve the global functioning of the schools and to reduce the percentages of smoking pupils and teachers. PMID- 11217244 TI - [Cost-benefit of the pharmacologic treatment of cerebral palsy with spasticity in Mexico]. AB - BACKGROUND: Cerebral palsy involving spasticity is a highly handicapping illness, especially among children, the treatment of which is limited to reducing the handicaps involved without any full cure. There is a drug treatment which affords the possibility of providing patients with a better quality of life, regarding which a cost effectiveness analysis is made, note being made of the individual achievements and social benefits. METHODS: This analysis is based on nationwide information from Mexico which was obtained from secondary sources. The base data is set out within the framework of trends in the growth of this health problem, and the calculations affording the possibility of sizing up this problem are employed in order to ascertain the benefits thereof based on the following indicators: relative impact of this disease and years of healthy life lost and gained, based on which the social and economic benefit entailed in the drug treatment under analysis is estimated. RESULTS: The data reveals that the drug treatment in question is directly beneficial, because it lowers the relative impact of this disease from 0.92 to 0.40. At the individual level, the greatest benefit takes the form of the improved quality of life among the afflicted children within the 6-12 age range, they having gone from 0.08 years to 0.60 years of life in terms of quality. At the nationwide level, the 595,817 years of healthy life which would be lost without any treatment would be recouped. The monetary value involved in this treatment is that of 2,725.00 Mexican pesos (US $283.00) for administering the drug over a one-year period to each child suffering from this disability. CONCLUSIONS: This is a low-cost treatment, because it is currently impossible to reverse the neurological and physiological processes of cerebral palsy, this treatment therefore improving the quality of life of the children afflicted with this disease is the best possible benefit. The cost effectiveness analysis taking into account these indicators reveals a clear-cut relationship between the monetary values and the health benefits. PMID- 11217245 TI - [Outbreak of gastroenteritis at a home for the aged in Albacete]. AB - BACKGROUND: We describe the investigation of an acute gastroenteritis outbreak with an explosive beginning, probably waterborne, that occurred in an nursing home in Albacete, in November 1999 and affected 104 inmates and 35 employees. The dominant symptoms were diarrhea and vomiting. METHODS: A case-control study was designed. We carried out a descriptive analysis of facts and crossing of variables with the help of simple tables. A multivariant analysis, by models of logistic regression, was conducted both for the explosive phase and for that of transmission person-to-person. RESULTS: The attack rate for inmates was 45.8% and for employees, 33.7%. An association was found between the use of the main dining room of the nursing home and the explosive beginning of the outbreak and between the previous presence of a case-patient in the shared bedrooms and the person-to person transmission. Norwalk-like virus was isolated from faeces samples of four cases. CONCLUSIONS: The analysis of the clinical and epidemiological findings as well as the laboratory results proved the implication of a Norwalk-like virus in this outbreak. PMID- 11217246 TI - [Horizontal transmission of tuberculosis in children at a day-care center]. PMID- 11217247 TI - [Methodologic obsession]. PMID- 11217248 TI - Information technology and ophthalmology. PMID- 11217249 TI - Ischaemic optic neuropathy. AB - Ischaemic optic neuropathy is of two types: anterior (AION) and posterior (PION), the first involving the optic nerve head (ONH) and the second, the rest of the optic nerve. Pathogenetically AION and PION are very different diseases. AION represents an acute ischaemic disorder of the ONH supplied by the posterior ciliary artery (PCA), while PION has no specific location in the posterior part of the optic nerve and does not represent an ischaemic disorder of any definite artery. The most important step towards a logical understanding of the underlying causes, clinical features, pathogenesis and rational management of AION, is to understand the basic scientific issues involved; these are discussed in some detail. AION clinically is of two types: (1) that due to giant cell arteritis (arteritic AION: A-AION) and (2) non-arteritic AION (NA-AION). NA-AION, the more common of the two, is one of the most prevalent and visually crippling diseases in the middle-aged and elderly, and is potentially bilateral. NA-AION is a multifactorial disease, with many risk factors collectively contributing to its development. Although there is no known treatment for NA-AION, reduction of risk factors is important in decreasing chances of involvement of the second eye and of further episodes. Our studies have suggested that nocturnal arterial hypotension is an important risk factor for the development and progression of NA AION. The role of nocturnal arterial hypotension in the pathogenesis of NA-AION and management of nocturnal hypotension is discussed. Potent antihypertensive drugs, when used aggressively and/or given at bedtime, are emerging as an important risk factor for nocturnal hypotension, and there is some evidence that NA-AION may be occurring as an iatrogenic disease in some individuals. A-AION, by contrast, is an ocular emergency and requires immediate treatment with systemic corticosteroids to prevent further visual loss. The clinical parameters which help to differentiate the two types of AION, and their respective management are discussed. PMID- 11217250 TI - Evaluation of children in six blind schools of Andhra Pradesh. AB - PURPOSE: 1. To determine the anatomical site and underlying causes of severe visual impairment and blindness in children in special education in Andhra Pradesh, India. 2. To compare the causes of blindness in two different regions in the state. 3. To evaluate improvement with correction of refractive error and low vision devices (LVDs). METHODS: Children in 6 schools for the blind and in 3 integrated education programmes were examined by one ophthalmologist, and were refracted and assessed for LVDs by an optometrist. The major anatomical site and underlying aetiology of severe visual impairment and blindness (SVI/BL; < 6/60 in the better eye) were recorded using the standardised WHO reporting form. RESULTS: Two hundred and ninety one students under 16 years were examined, and after refraction, 267 (91.7%) were classified as being severely visually impaired or blind. The most common anatomical sites of SVI/BL were retina in 31.1% children; cornea in 24.3%; and whole globe in 20.2%. The aetiology was unknown in 38.2%, hereditary in 34.8% and childhood causes in 24%. 114 children (39.2%) had functional low vision (i.e. visual acuity < 6/18 to light perception with navigational vision). In this group, 36 children improved with spectacles and 16 benefited by LVDs. 41 children (15.4%) were able to read N10 point though they were studying Braille. CONCLUSION: Overall 37.4% of children had "avoidable" causes of blindness. The major avoidable causes were vitamin-A deficiency and cataract. Vitamin-A deficiency and congenital anomalies were more common in the dry plateau areas of the state. One in seven children could read normal print with optical support. PMID- 11217251 TI - A retrospective study of low-vision cases in an Indian tertiary eye-care hospital. AB - PURPOSE: To obtain data on the characteristics of low-vision patients seen at a tertiary eye care hospital in India. METHODS: Records of 410 patients were retrospectively reviewed at the Centre for Sight Enhancement, L.V. Prasad Eye Institute, Hyderabad, India. Patient underwent a comprehensive clinical low vision examination. Data obtained included age, gender, consanguinity, visual acuity, visual fields, ocular conditions causing low vision and types of low vision devices and methods prescribed. RESULTS: Two hundred and ninety seven (72%) of 450 patients were male. One-fifth were in the 11-20 years age group (21%). Visual acuity in the better eye was < 6/18-6/60 in almost half these patients (49.3%). One hundred and twenty two patients (29.9%) referred with a visual acuity of > or = 6/18, either had difficulty in reading normal print or had restricted visual fields. The main causes for low vision were: retinitis pigmentosa (19%), diabetic retinopathy (13%), Macular diseases (17.7%), and degenerative myopia (9%). Visual rehabilitation was achieved using accurate correction of ametropia (174 patients), approach magnification (74 patients) and telescopes (45 patients) for recognising faces, watching television and board work. Spectacle magnifiers (187 patients), hand/stand magnifiers (9 patients), closed-circuit television (3 patients), overhead illumination lamp (143 patients) and reading stand (24 patients) were prescribed for reading tasks. Light control devices (146 patients) were used for glare control, and cane (128 patients) and flashlight (50 patients) for mobility. Patients were trained in activities to improve their daily living skills, (54 patients); counselled in environmental modification (144 patients) and ancillary care (63 patients) for educational and vocational needs. CONCLUSION: Data obtained from this study elucidates the characteristics of low-vision patients. This information is likely to help in the development of appropriate low vision services. PMID- 11217253 TI - Is pseudophakic astigmatism a desirable goal? AB - PURPOSE: To determine whether pseudophakic astigmatism is a desirable goal, and if so, which one is better: against-the-rule (ATR) or with-the-rule (WTR). METHOD: Eyes were included only if they had an uncorrected vision > or = 6/18 and N/18. Three groups, of 40 patients each were evaluated: group 1, pseudophakes with neutral astigmatism; group 2, with ATR and group 3, with WTR astigmatism Unaided distance and near visual acuity was recorded. Statistical analysis was performed using the chi-square test for independence. RESULTS: Unaided distance vision of > or = 6/7.5 was achieved in 19 eyes (47.5%) of group 1 (neutral), 12 eyes (30%) in group 2 (ATR), and 5 eyes (12.5%) in group 3 (WTR) (p = 0.0133, significant). Unaided near vision of > or = N/9 was achieved in 17 eyes (42.5%) in group 1 (neutral), 34 eyes (85%) in group 2 (ATR), and 10 eyes (25%) in group 3 (WTR) (P < 0.001, significant). Group 1 (neutral) fared the best for unaided distance visual acuity. Group 2 (ATR) was better than in group 3 (WTR) for distant vision. Group 2 (ATR) fared the best for unaided near vision. CONCLUSION: ATR astigmatism could be a desirable goal after cataract extraction in selected populations because the largest proportion of these cases achieved good unaided near vision with acceptable distant vision. PMID- 11217252 TI - Partial flap during laser in-situ keratomileusis: pathogenesis and timing of retreatment. AB - PURPOSE: To report the timing of retreatment and clinical outcomes in patients with a partial corneal flap during laser in-situ keratomileusis (LASIK), and to describe the causes of this complication. METHODS: Retrospective review of case records of four patients (4 eyes) who had a partial corneal flap during LASIK. RESULTS: The mean age of the four patients was 23 +/- 4.7 years, and mean preoperative spherical equivalent (SE) refraction was -9.1 +/- 3.1 D (range, -5.5 to -13 D). A 160 microns corneal flap was attempted during the initial treatment. Retreatment with a 180 microns corneal flap was performed at a mean of 5.1 +/- 1.6 weeks (range, 4 to 7.5 weeks) after the initial procedure. There were no intraoperative complications during retreatment. Post-LASIK mean SE refraction was -1.0 +/- 1.1 D (range, +0.38 to -2.0 D), after a mean follow up of 19 +/- 15.7 weeks (range, 7 to 42 weeks). Best spectacle-corrected visual acuity decreased in one eye from 6/5 to 6/6 and was maintained in the others. CONCLUSION: LASIK retreatment can be performed as early as one month after a partial flap, if the refraction is stable and a thicker corneal flap is created. PMID- 11217254 TI - Nocardia Asteroides keratitis: report of seven patients and literature review. AB - PURPOSE: To describe clinical features and treatment outcomes in patients with advanced Nocardia asteroides keratitis. METHODS: Retrospective review of case records of 7 patients with culture-proven Nocardia keratitis. RESULTS: Corneal infection occurred after corneal trauma in two patients, cataract surgery in three patients, penetrating keratoplasty in one patient and was associated with a silicone buckle element infection in one patient. Mean duration of infection at presentation was 33.4 days (7-75 days), and five patients had received prior treatment with corticosteroids. Six of seven patients had deep corneal suppuration at the time of presentation, clinically suggestive of mycotic keratitis. In two patients who had received prolonged corticosteroid therapy (> or = 45 days), the eyes could not be salvaged. Complete resolution of infection was achieved in all 4 eyes treated with topical fortified cefazolin eye drops (50 mg/ml). PMID- 11217256 TI - Management of anterior segment penetrating injuries with traumatic cataract by Pentagon approach in paediatric age group: constraints and outcome. AB - PURPOSE: To evaluate the efficacy of multiple combined procedure (Pentagon approach) as single-step secondary repair in cases of extensive keratolenticular trauma in paediatric age group. METHODS: Retrospective evaluation of 18 patients of penetrating injuries with sclerokeratolenticular trauma, who underwent multiple procedure as single-step secondary repair by a single team of two surgeons during a 4 year period. Surgical procedure included reconstruction of anterior segment, synechiolysis, excision of membrane, lensectomy, open sky vitrectomy, PC IOL implantation over frill and penetrating keratoplasty. Meticulous antiamblyopia measures were applied in all cases. RESULTS: Extensive vasoproliferative membrane, complicated cataract and anterior vitreous condensation were significant intra-operative hurdles. Moderate uveitis, secondary glaucoma, persistent epithelial defects were problems noted. Eleven (61.22%) patients attained good visual outcome. Regrafting was required in remaining cases due to delayed graft failure. CONCLUSION: Despite being a highly complex technique, Pentagon approach provides effective management profile in terms of graft success and functional outcome, especially in keratolenticular trauma, in children. PMID- 11217255 TI - Topical diclofenac sodium for treatment of postoperative inflammation in cataract surgery. AB - PURPOSE: To study the effect of a topical non-steroidal anti-inflammatory drug as an alternative to topical steroids for postoperative control of inflammation in cataract surgery. METHODS: The effect of diclofenac sodium 0.1% following cataract surgery was studied and compared to routine corticosteroid, dexamethasone phosphate 1% in a prospective, double-blind randomized study. Both groups were similar in baseline parameters. Postoperative inflammatory response, intraocular pressure and best-corrected visual acuity following standard extracapsular cataract extraction were assessed in both groups in the initial 21 days and the severity of these parameters was graded. The severity of postoperative inflammatory response to the two drugs was graded at 1, 3, 7, 14 and 21 days. Intraocular pressure and visual acuity at baseline and endpoint were compared and statistically analyzed. RESULTS: The two groups did not differ statistically in treatment effect for any of the variables including aqueous cells, flare, ciliary congestion, Descemet's folds, visual acuity and intraocular pressure (p < 0.001). However there seemed to be a trend towards quicker improvement with corticosteroid when cells in the anterior chamber were considered. There were no side effects from topical diclofenac, and it was well tolerated. CONCLUSION: Diclofenac sodium is as effective as topical corticosteroid and can be used as an alternative in routine postoperative treatment following uncomplicated cataract surgery. PMID- 11217258 TI - Unilateral pellucid marginal degeneration. AB - Pellucid marginal degeneration (PMD) is a rare and usually a bilateral condition. We report a case of typical PMD with a unilateral presentation. PMID- 11217257 TI - Lid swelling and diplopia as presenting features of orbital sarcoid. AB - Sarcoid is an idiopathic multisystem non-caseating granulomatous disease with protean clinical manifestations. In the eye, the common sites of involvement are the skin of eyelid, conjunctiva, uveal tract, retina, optic nerve and lacrimal gland. PMID- 11217259 TI - Phakic-pseudophakic bullous keratopathy following implantation of a posterior chamber IOL in the anterior chamber to correct hypermetropia. AB - There is an increasing demand for refractive surgery stemming from a heightened awareness among patients wearing spectacles or contact lenses. Cosmetic or occupational reasons prompt patients to seek the alternative option of refractive surgery. PMID- 11217260 TI - The impact of information technology on the practice of ophthalmology. AB - Information technology has had a tremendous impact on the outlook of our professional lives. The Internet has revolutionised the speed of access to information with touch of a button. This article discusses the various aspects of information technology which are changing and enhancing our professional lives. It provides tips to enable the busy practising clinician to use the available resources effectively. Problems such as reliability of information on the web and how to assess the quality of such matter are also discussed. PMID- 11217261 TI - Sample size for ophthalmology studies. AB - Knowledge and the usage of actual sample size formulae are a necessity as validity of the inferences from research studies is often dependent on this. This paper explains how sample sizes are calculated. The concept of sampling variation is explained to emphasize the need for its proper calculation. Sample size formulae are explained with examples to provide researchers with a means of calculating the sample sizes for the commonly used study designs. Ophthalmic data are used as examples. It is perceived that this will improve the quality of inferences drawn from ophthalmic research studies. PMID- 11217262 TI - Safety of oral methotrexate pulsed therapy. PMID- 11217263 TI - Hepatitis C infection and recent diagnostic modalities. PMID- 11217264 TI - Aspiration vs nonaspiration technique of cytodiagnosis--a critical evaluation in 160 cases. AB - The two sampling techniques were studied in 160 randomly selected cases of superficial swellings in various sites of the body. They were sampled by fine needle aspiration (FNA) and by non-aspiration (NA) (a needle without application of aspiration pressure). Cell samples were cytologically assessed and critically evaluated using five objective parameters. Contamination with blood was more in lymphnode, thyroid and liver lesions in aspiration smears than NA smears and values were statistically significant. Similarly when compared for the degree of cellular trauma and cellular degeneration statistically significant better results were obtained by nonaspiration technique for lymphnode lesions. Regarding amount of cellular material obtained by FNA, statistical significant better results were found for breast lesions only. Statistically significant better maintenance of architecture was observed only for thyroid lesions by NA technique. Better average scores were observed by NA technique for lymphnode and thyroid only. Categorizing all the smears obtained by FNA & NA on the basis of their scores according to predetermined criteria, greater number of diagnostically adequate specimens were obtained by FNA than by NA but the number of diagnostically superior specimens obtained by NA technique was found to be more than that by FNA. The difference was found to be statistically significant. However the number of inadequate smears was also more by NA technique than by FNA technique. PMID- 11217265 TI - Sex cord-stromal tumours of the ovary. A clinicopathological spectrum. PMID- 11217266 TI - A study of lupus anticoagulant in unexplained fetal wastage. AB - Lupus Anticoagulant, first discovered in patients of SLE, is now known to be associated with a wide spectrum of diseases. The presence of LA is associated with adverse fetal outcome in an obstetric population. In the present series the incidence of LA was found to be 16.6% and 80% of LA positive subgroup had an unsuccessful outcome. PMID- 11217267 TI - DNA flow-cytometry on fine needle aspiration cytology of lymph node: how helpful is it? AB - The diagnostic value of DNA content analysis by flow cytometry (FCM) has rarely been evaluated in combination with fine needle aspiration cytology (FNAC). In this present study, the value of DNA FCM in distinguishing malignant lesions from benign enlarged lymph nodes on FNAC material has been investigated. DNA FCM was done from FNAC materials of 58 cases of lymph node swellings Becton Dickinson's flow cytometer (USA) along with 'Cell Quest' program was used for the analysis of DNA ploidy and S & G2-M phase cells. There were 16 cases of reactive lymphoid hyperplasia, 8 cases of metastatic carcinoma and 34 cases of non Hodgkins lymphoma (NHL). DNA FCM showed 12 aneuploid case and 46 diploid case. All the cases with DNA aneuploidy were malignant. None of the benign cases showed aneuploidy on DNA aneuploidy were malignant. None of the benign cases showed aneuploidy on DNA histogram. Out of the 46 diploid cases, 11 cases showed high S & G2-M Phase cells (> 10%). Nine out of these 11 cases were malignant on FNAC. The sensitivity and specificity of DNA FCM were 50% and 87.5% respectively. None of the low grade NHL was detected by DNA FCM. In conclusion, DNA aneuploidy and high G2-M phase cells (> 10%) are good indicators of malignancy in lymph node aspirate. However DNA FCM is relatively costly and thereby its role as an adjunctive technique needs careful re-evaluation. PMID- 11217268 TI - Collagenous spherulosis of breast: diagnosis by FNAB with review of literature. AB - Collagenous Spherulosis (CS) of breast is an innocuous but interesting uncommon morphological feature observed with a variety of benign and malignant breast lesions. We report a case of collagenous shperulosis associated with nodular sclerosing adenosis (Adenosis tumor) on fine needle aspiration (FNA) smears confirmed later by biopsy. The differential diagnosis of collagenous spherulosis is discussed. PMID- 11217269 TI - Multidrug resistant Salmonella typhi in Rourkela, Orissa. AB - Out of 5410 blood samples 715 samples were found positive for Salmonella typhi. Enteric fever was prevalent for last three years in Rourkela. In last two years, a number of multidrug resistant strains of Salmonella typhi was isolated which constituted almost 16.1% of the total isolates. In this study, chloramphenicol sensitivity was found quite high (86.5%) and ceftriaxone showed 100% sensitivity. Resistance to ciprofloxacin was found 2.5% which due to direct consequence of indiscriminate use of antibiotics, either singly or in combination. PMID- 11217270 TI - In vitro susceptibility testing of nonsporing anaerobes to ten antimicrobial agents. AB - Antibiotic Susceptibility was performed on sixty clinical isolates of nonsporing anaerobes against ten antimicrobial agents. The test was performed on Muller Hinton Agar and Wilkins Chalgren blood agar by preparing suspension of freshly isolated colonies in BHI broth. Apart from Metronidazole and Chloramphenicol newer antibiotics like Minocycline, Secnidazole, Tinidazole, Clarithromycin, Roxithromycin were also tried. Antimicrobial agents like metronidazole, Secnidazole, Tinidazole and Minocycline were 100% sensitive, followed by Chloramphenicol, Clarithromycin and Roxithromycin. These newer agents can be good alternatives for the treatment of non sporing anaerobes. PMID- 11217271 TI - Comparison of Vitek Yeast Biochemical Card with conventional methods for speciation of Candida. AB - The ability of the Vitek Yeast Biochemical Card to identify yeast isolates was compared with conventional methods. Of the fifty yeast isolates tested same species identification was obtained in thirty-four isolates. The Vitek yeast biochemical card identified 13 isolates which could not be identified by the conventional tests. Though the Vitek Yeast biochemical card gave a good rapid identification the high cost of each test severely limits its routine use in most of the laboratories. PMID- 11217272 TI - Gall stones and carcinoma gall bladder. AB - One hundred and fifty surgically resected gall bladder specimens were included in the study to evaluate the relationship between the prevalence of gall stones and histochemical alteration in sequential changes of metaplasia, dysplasia and neoplasia in gall bladder epithelium. Multiple sections were processed and stained with haematoxylin and eosin, Periodic acid Schiff's stain, Alcian blue (pH 2.5)/Periodic acid, Orcein/Alcian blue (pH 2.5) and Alcian Blue/Periodic acid/Potassium borohydride saponifications stains. Details of gall stones present were also noted. Prevalence of gall stones in gall bladders with metaplastic, dysplastic and neoplastic mucosal changes was significantly higher (P < 0.001) than those gall bladders which had no epithelial changes. Increase in sialomucin with a corresponding decrease in sulphomucin was observed from metaplasia to malignancy. Neutral mucin increased in metaplastic cells but was significantly reduced in neoplastic cells. Loss of O-acylation in sialmucin was also present in neoplastic cells. The histochemical changes suggest that chronic injury due to cholelithiasis induces appearance of neutral mucin positive metaplastic cells, which may further dedifferentiate to sialomucin containing dysplastic or neoplastic cells if the stimulation persists. PMID- 11217273 TI - Giant cell tumour of soft tissue--a case report. AB - Giant cell tumor is seen in late adolescence or in the third or fourth decade of life. It arises from epiphysis of long bones, the commonest site being the distal end of the demur and the proximal end of tibia. This paper presents a case report of giant cell tumor of soft tissue. PMID- 11217274 TI - Retroperitonial atypical lipomatous tumour--a case report. AB - We report a case of atypical lipomatous tumor-sclerosing type, a rare retroperitoneal soft tissue liposarcoma, presented with vague musculoskeletal symptoms. Patient was managed with complete resection of the tumor mass with adjuvant chemotherapy. The patient is doing well, with no evidence of recurrence 22 months after the treatment. PMID- 11217275 TI - Primary intracranial chondrosarcoma--a case report. AB - Intracranial malignant cartilaginous tumors, not arising from the skull bones are a rare phenomenon, and few cases have been reported till date in literature. We hereby describe one such case treated by us. PMID- 11217276 TI - Histoplasma capsulatum in adrenal gland aspirate--a case report. AB - We report a case of disseminated histoplasmosis in a 60-year-old non immunocompromised patient who presented to us with fever and hepatosplenomegaly. Sonographic & CT examination of the abdomen showed bilateral adrenal masses. Cytological examination of the aspirated material from the mass showed yeast forms of H. capsulatum. PMID- 11217277 TI - Aeromonas caviae as a cause of cholecystitis. PMID- 11217278 TI - Epidemiology of epilepsy--recent achievements and future. AB - Epilepsy is a very common neurological disease. Reliable epidemiological data are of great importance for understanding the etiology and risk factors for its development. It is necessary to use standardized methodology for the results from epilepsy studies in different geographical regions to be comparable. Most of the epidemiological studies of epilepsy find an incidence rate of 20-70/100,000 per year (range 11-134/100,000). The state of the problem in Bulgaria and other countries of Eastern Europe is not adequately studied. It is considered that the figures are higher in the developing countries. Incidence is higher in men than in women and varies considerably with age--it is high in childhood, decreases in young people and rises again in the elderly. Only approximately 30% of the newly registered cases can be assigned to one of the diagnostic categories. The studies identify an etiological factor in only about one third of all cases. The most commonly reported etiological factors are: cerebro-vascular disease, tumors, alcohol, head injuries, congenital factors and neuroinfections. Most of the developed countries report prevalence of active epilepsy in the range of 4 8/1000. The prevalence rates in Latin America and some African states are especially high. In Bulgaria by means of the system of regional psychoneurological dispensaries about 30,000 epilepsy patients are registered, but it may be assumed that their real number is over 60,000. Contemporary views on the prognosis of this disease are favorable--more than 70% of the diseased reach long-term remission. Different prognostic factors predicting the final outcome of epilepsy patients are described. Epilepsy patients exhibit more than 2 times higher mortality rate than the expected rate for the corresponding population. It is necessary to conduct additional projects, based on the available standardized methodology for epidemiological monitoring of epilepsy in different geographical regions, including Bulgaria. PMID- 11217279 TI - A study of Helicobacter pylori infection in patients with pernicious anemia. AB - INTRODUCTION: Chronic atrophic gastritis presents with atrophy of the gastric mucosa, hypochlorhydria or achlorhydria and unstable gastrin level. Type A chronic atrophic gastritis associated with hypergastrinemia is regarded as the principle causative factor for pernicious anemia. AIM: The study aimed at evaluation of the incidence of H. pylori infection in patients with pernicious anemia and analyze its relation to the severity of gastritis. MATERIAL AND METHODS: Forty patients with pernicious anemia (group 1) were examined for presence of H. pylori infection. Sex- and age-matched patients with gastric ulcer (group 2) and chronic superficial gastritis (group 3) were used as controls. Three antral forceps biopsies were obtained from all patients during videogastroscopy. The presence of H. pylori was verified by urease test, histological and microbiological examination. RESULTS: All patients with pernicious anemia had chronic atrophic gastritis and several times lower incidence of H. pylori infection than the patients with gastric ulcer. Chronic atrophic gastritis was not diagnosed in group 3 patients. Statistically significant difference in Helicobacter pylori infection was found between groups 1 and 2 (P < 0.001) but not between groups 1 and 3 (P > 0.05). CONCLUSIONS: Atrophic gastritis was diagnosed in all patients with pernicious anemia. These patients showed significantly lower incidence of H. pylori infection than the gastric ulcer patients. The patients with pernicious anemia had lower gastritis index and quantitatively less expressed infection than the other two groups. PMID- 11217280 TI - Influence of age, sex and body weight on renal osteodystrophy in predialysis patients with chronic renal failure. AB - The aim of the present investigation was to examine the influence of age, sex and body weight on osseous changes in pre-dialysis patients with chronic renal failure (CRF). 87 patients (44 males and 43 females) aged 18-60 years with CRF were studied. The levels of serum creatinine, total and ionized calcium, phosphorus, alkaline phosphatase, intact parathormone and serum osteocalcine were followed up. Body weight is presented as BMI. 47 of the patients were subjected to double X-ray absorptiometry of lumbar vertebra (Lunar) and 40 patients were examined by computed tomography osteometry. RESULTS: No reliable differences in the levels of biochemical parameters in male and female patients with the same degree of CRF were established. A tendency towards an increase in the level of intact parathormone and serum osteocalcine in women with both initial and advanced CRF was recorded. The BMI in patients with advanced CRF was lower as compared to those with initial CRF. Different stages of osseous changes were observed in 29 males (74.35%) and in 25 females (60.97%). A tendency for a higher frequency and severity of osseous changes in men aged up to 40 years was observed. After this age males and females were equally affected. A high positive correlation (r = 0.50) between BMI and the percentage of the normal Bone Mineral Density/Bone Mineral Content in females with CRF stage II and III was noticed. CONCLUSIONS: No significant difference in the frequency and severity of osseous changes in male and female uremic patients was observed. Bone changes were more frequent and pronounced in males up to 40 years of age, while this tendency reversed after the menopause. The higher body weight was beneficial for the osseous changes only in females with advanced CRF, while in all other patients no correlation with densitometric parameters was noticed. PMID- 11217281 TI - Low protein diet and ketosteril in predialysis patients with renal failure. AB - After a short review of the contemporary understanding of amino acid supplementation to low protein diets in patients with uremia we present the results of administration of ketosteril in 20 low-protein-diet patients on such a diet. MATERIAL AND METHODS: Twenty patients (10 men and 10 women) with stable II and III stage chronic renal failure were assigned to a low protein diet (protein up to 40 g/day). Ketosteril (6 tablets a day) were added to the diet. Some of the basic markers of protein metabolism and nitrogen balance were followed. RESULTS: No evidence of deteriorated protein synthesis was found in the therapy thus administered. Serum urea and creatinine values did not change and even tended to decrease. Glomerular filtration was found to increase insignificantly more markedly in the patients with renal failure in the early stages. CONCLUSIONS: A low protein diet with increased content of essential amino acids and their keto analogues does not deteriorate the nitrogen balance of patients with chronic renal failure. By adding essential amino acids and keto-analogues a normal protein metabolism is maintained in spite of the reduce intake of protein substances with the diet. Supplementation of the diet of chronic renal failure patients with essential amino acids and keto-analogues allows a considerable reduction of the protein intake to be achieved which brings about reduction of glomerular hyperfiltration which actually retards the progression of renal failure and improves its short-term prognosis. PMID- 11217282 TI - Cyclosporin A in the treatment of patients with nephrotic syndrome. AB - OBJECTIVE: To present our experience in the treatment of conventional therapy refractory nephrotic syndrome with cyclosporin A. MATERIAL AND METHODS: The study sample included 22 patients (12 men, 10 women, aged 40.43 +/- 5.93 years). Twenty one patients were diagnosed histologically: 11 were with different histologic variants of chronic gtlomerulonephritis, 7 with lupus nephritis and 3 with renal amyloidosis. Sandimmun Neoral-Sandoz was given orally in a dose of 2-5 mg/kg/24 hours; mean duration of the course of treatment 41.4 +/- 12.4 days. In the course of treatment we followed quantitatively 24-hour proteinuria, diuresis, hematologic parameters, serum creatinine, transaminases, the fat profile, and creatinine clearance. RESULTS: The patients were allocated into 3 groups according to their response to treatment--in 5 patients (22.73%) it achieved complete clinical and laboratory remission, in 8 (36.36%)--partial remission and in 9 (40.91%) it failed. The 24-hour diuresis in the patients with complete and partial remission increased significantly during the third week of treatment (from 1212.5 +/- 114.7 to 2700 +/- 394.61, p < 0.05, t = 3.62). Proteinuria was reduced from 3.47 +/- 0.54 to 1.86 +/- 0.36 g/d (p < 0.05, t = 2.48) at the end of treatment. No substantial change in the antihypertensive therapy was necessary in any of the patients. There was no decline of the renal and liver functions. Neither allergic reactions nor serious side effects that may have caused discontinuation of treatment were observed. Complete or partial clinical and laboratory remission was achieved in 59.09% (13 patients) (confidence interval = 39.2%-78.9%, odds ratio = 0.95). Cyclosporin A therapy is an appropriate alternative in the treatment of refractory nephrotic syndrome in some of the immunologic glomerulopathies. The types of glomerulopathy that are best affected are minimal-change glomerulonephritis, some of the mesangioproliferative glomerulonephritis cases and some forms of lupus nephritis. No effect whatsoever was found in cases with renal amyloidosis. PMID- 11217283 TI - Acute hemolytic anemia as an initial clinical manifestation of Wilson's disease. AB - Wilson's disease is an inherited disorder of copper transport in the organism, transmitted in autosomal recessive fashion. It is caused by dysfunction in homologous copper-transporting adenosine triphosphatases. The main clinical symptoms are usually due to hepatic (42%) or/and neurologic (34%) involvement, which is the reason for the name hepatolenticular degeneration. Described in this report are four cases--the first three demonstrate an unusual form of manifestation of Wilson's disease in clinical practice--glucose-6-phosphate dehydrogenase deficiency hemolytic anemia. The fourth case concerns acute intravascular hemolysis that was provoked by the disease and presented without erythrocyte enzyme disturbances. Hemolytic anemia is a recognized but rare (10 15%) complication of the disease. Most often Coombs' negative acute intravascular hemolysis occurs as a consequence of oxidative damage to the erythrocytes by the higher copper concentration. A literature review with discussion of the possible mechanisms for the development of this phenomenon is done. PMID- 11217284 TI - Myoplasty in chronic osteomyelitis and other postoperative defects of the lower jaw. AB - BACKGROUND: Mandibular chronic osteomyelitis is a complicated therapeutical problem in the oral and maxillofacial surgery. While the principles of conservative and radical treatments are generally widely accepted by all authors, the repair of the defects by plastic surgery is inadequately developed. METHOD: Eleven patients with chronic osteomyelitis, odontogenic cysts and benign tumors of the mandible were treated by filling the osseous defect with a muscle flap from the adjacent m. masseter, m. buccinatorius and m. platysma. RESULTS: The clinical and X-ray examinations showed that a successful outcome without complications was achieved in all treated patients. There was no recurrence of the underlying disease in the five-year follow-up period. CONCLUSIONS: Use of muscle pedicle flaps for plastic reconstruction of osteomyelitic cavities and other osseous defects improves the effect of the treatment, shortens its duration and reduces the possibility of further recurrences of the disease. PMID- 11217285 TI - Undergraduate medical education: tendencies and requirements in a rapidly developing Europe. AB - This study pinpoints the necessity to constantly monitor local approaches in undergraduate medical education on an inter-European scale. Traditional undergraduate medical curricula need restructuring to account for the increasing amount of medical knowledge and rapid changes and developments in societies, nosology, therapy and IT. European undergraduate medical curricula should be harmonized not egalized, with a focus on inter-European sharing of resources, mobility, credit (allocation, accumulation and transfer), definition of European and trans-European mission statements, identification of quality metrics, advice on dealing with conflicting aims such as specialization and generalization, on communicating core knowledge instead of providing overabundance of information, and on introducing multifaceted teaching and learning methods, as well as providing strategies for life long learning. Sound medical education can no longer and nowhere be considered under the autonomous auspices of individual Medical Schools or national philosophies. It has to be perceived and structured as a competitive and flexible approach which promotes life long learning of teachers, students, physicians and other related staff with international awareness. It is stressed that student and staff mobility, as well as virtual mobility in the form of worldwide available teaching modules and expertise have to be incorporated into national medical curricula. This is to guarantee up-to date education in support of patient demands, future professionality and competitiveness of students, physicians and Public Health System institutions. The formal approaches of traditional subject related curricula as well as problem based learning must be linked with quality approved state of the art ODL, evaluated international CME strategies and training in the utilization of IT in preparation of lifelong learning. Strategies for the use of IT need updating on a regular basis to diminish the gap between undergraduate and postgraduate medical education. General European perspectives of medical education are discussed in relation to ECTS, ODL, compulsory credited and evaluated CME and relicensing of physicians. Prime features of ETM--the most reputed and well-known European medical CME initiative fostering quality assured international awareness are described and recommended for local and nationwide implementation. Specific links of the Bonn undergraduate medical curriculum with credited and evaluated CME and imminent European strategies are detailed. The authors conclude that European universities not adapting at least some of the outlined curricular necessities will rapidly lose their competitiveness compared to other national and international Medical Schools. Harmonized European ethical mission statements and consequent utilization of IT deserve special considerations in this context. PMID- 11217286 TI - Endonasal microscopic dacryocystorhinostomy: results and advantages. AB - BACKGROUND: The modern endonasal operative technique of functional fenestration of saccus lacrimalis in the middle nasal meatus (endonasal dacryocystorhinostomy), first described by West in 1910, has been gaining in significance over the past few years. At the VI National Congress of Otorhinolaryngology (1997) we presented for the first time in this country performance of endonasal microscopic dacryocystorhinostomy videotaped and started a routine use of this technique in our department. OBJECTIVE: We present the results of our 3-year experience with the technique. MATERIAL AND METHODS: Endonasal microscopic dacryocystorhinostomy was performed in 50 patients (57 operations) without stenting. The effect of the surgery was assessed by comparing the results of control examinations with the preoperative findings using the following criteria: subjective complaints, and objective findings--palpatory test, irrigation according to Anell, endoscopy of the nasal cavities and the neo ostium. RESULTS: Statistically significant improvement of specific subjective symptoms was obtained in 78.9%-100%. In 6 cases the closure of the neo-ostium was proven endoscopically. CONCLUSION: Endonasal microscopic dacryocystorhinostomy preserves intact the normal function of the lacrimal pump, yields excellent cosmetic results and allows simultaneous management of the concomitant sino-nasal pathology. A neo-ostium under 2 mm in diameter can be conducive to postoperative epiphora. A congenital, untreated form of postsaccal stenosis with concomitant dacryocystitis as well as formation of synechiae are factors increasing the possibility of restenosis. PMID- 11217287 TI - Surgical correction of funnel chest. AB - AIM: To present our experience in surgical treatment of funnel chest. MATERIAL AND METHODS: Seven patients (6 males and 1 female) aged 13 to 18 years were treated in the Department using Rathke-Schlegel's modification of Ravitch operative technique. In 2 patients the corrected deformity status was maintained by 2 Kirschner's pins that were placed substernally and attached bilaterally to the adjacent ribs. In one patient a direct traction through the sternum was applied and in 4 patients the fixation was achieved by fastening the sternum with wire loops to an overlying AO plate. RESULTS: Very good results were achieved in 4 patients (57.14%) and a good outcome was evaluated in 3 patients with 30% recurrence of the deformity. There was no lethal outcome. Three complications were encountered: in one patient hemothorax occurred that was cured by a single punction aspiration, in other patient one of the Kirschner's pins slipped into the thoracic cavity. The pin but did not injure intrathoracic organs and was promptly removed. In the third patient earlier removal of the plate was required because suppuration developed. CONCLUSION: The presented method for correction of chest deformity is successful if the implants are kept in place from 6 to 12 months. This time is sufficient for formation of a solid callus that prevents recurrence of the deformity. PMID- 11217288 TI - Dynamics of potassium and nitrate ions release from polycarboxylate cement with 5% KNO3. AB - Release of potassium and nitrate ions from polycarboxylate-cement blocks containing 5% KNO3, with different exposure in extragent aqua redestillata was studied. Using flame photometry we found increased concentration of eliminated potassium ions into the extragent after the 24th hour (0.90 +/- 0.03 mg/cm3) while the maximum quantity of released potassium ions was measured after the 14th day (336 h)--1.50 +/- 0.02 mg/cm3 (t = 60, P < 0.001). The concentration of the released nitrate ions was determined by spectrophotometry at l = 410 nm. The degree of extraction of nitrate ions from the model cement blocks progressively increased with time, but their concentration in the cement decreased after the 14th day too, demonstrating a statistically significant difference: from 4.50 mg on the 20th minute to 2.60 mg on the 14th day (t = 115, P < 0.001). PMID- 11217289 TI - Mandibular fractures in children. A retrospective study. AB - This study reviews the treatment of mandibular fractures in children for the period 1986-1995. The sample included 107 children under 15 years of age, which were studied by age, sex, cause and type of fracture, method of treatment and complications. The children were divided into four groups according to the development of the dentition: 0-5 years, 6-9 years, 10-12 years and 13-15 years. Boys to girls ratio was 3.46:1 and the highest incidence was observed in boys over 13 years of age. Associated injuries were more common in younger children (56%). Most of the fractures were the results of traffic accidents (28.97%), games and sports (25.23%), beating (19.63%) or falls (15.88%). Unilateral fractures were more common (69.16%) than bilateral (30.84%). Intermaxillar fixation for 3 weeks was the method of treatment used in 84.12% of the patients. Complications appeared to be rare. PMID- 11217290 TI - Morphological changes in dental enamel after fluoride gel application in vitro. AB - INTRODUCTION: The investigations of in vitro models precede the clinical studies. Using these studied we can investigate the effect upon the enamel of different agents for local application. AIM: The purpose of this study was to investigate the ultrastructural changes in a normal and partially demineralized enamel after 0.42% fluoride gel application in vitro using scanning electron microscopy. MATERIAL AND METHODS: The experiment was performed on 20 premolars extracted for orthodontic indications. Symmetrical specimens were prepared, as one half served as a control, while the other one was treated with fluoride gel. The specimens were examined with electron microscope at different magnifications. RESULTS: The findings show that fluoride gel applications affect the processes of mineralization and remineralization. CONCLUSIONS: This gives us the ground for applying fluoride gel in the clinical practice for prevention and treatment of caries incipiens. PMID- 11217291 TI - Caries incipiens prevalence of the permanent teeth by jaw regions in 7-, 12- and 14-year-old children. AB - AIM: The purpose of the present study was to establish caries incipiens prevalence of the permanent teeth by dental surfaces (Is). Caries incipiens is examined totally and separately by macula cariosa alba and macula cariosa fusca by jaws and regions. MATERIAL AND METHODS: The sample is random and comprises 600 children of 7, 12 and 14 years of age. Caries incipiens is diagnosed visually tactile by means of a probe and mirror. The data is analyzed statistically with Excel 7.0. Statistical significance was defined as 0.05, two-tailed. RESULTS: Caries incipiens prevalence is highest at 7 years and does not change considerably with increase of age. In all age groups macula cariosa fusca prevalence is higher than that of macula cariosa alba (P < 0.001). The highest prevalence of macula cariosa fusca is found occlusally in all age groups in both jaws. Overall compared to the upper jaw prevalence rates in the lower jaw are higher. CONCLUSION: The obtained results are of importance in designing and applying preventive programs. PMID- 11217292 TI - Gingivoperiosteoplasty in 3-to-5-year-old patients with cleft lip and palate: a preliminary communication. AB - Closure of the alveolar cleft and the oronasal fistulas was achieved by gingivoperiosteoplasty in 26 patients with unilateral or bilateral cleft of the lip and palate. They were divided in two groups according to whether or not functional cheiloplasty was previously performed (group I comprised 12 patients, group II--14 patients). No systemic pre- or post-surgical orthodontic treatment was administered in both groups. The malocclusions before and after gingivoperiosteoplasty, the postoperative fistulas and the speech were evaluated. Prior to gingivoperiosteoplasty malocclusions were found in 16 children (4 in group I and 12 in group II). After gingivoperiosteoplasty better occlusion was achieved in 6 patients of group II and in 3 of group I. Malocclusions remained in 6 children of group II and in one of group I. Fistulas persisted in 3 children (group II--2, group 1--1). Rhinolalia was found in 7 children of group II and in none of group I. In conclusion, we think that gingivoperiosteoplasty can be performed successfully after eruption of the deciduous teeth, that is between 3 and 5 years of age. The quality of the cheiloplasty and palatoplasty performed prior to it is of great significance. Gingivoperiosteoplasty should be included as a separate surgical stage in the management of total cleft lip and palate. PMID- 11217293 TI - The most frequently cited articles published in Social Biology, 1961-1999. PMID- 11217294 TI - The founding of the Behavior Genetics Association, 1966-1971. PMID- 11217295 TI - MMPs and TIMPs. An historical perspective. PMID- 11217296 TI - The matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) genes. Transcriptional and posttranscriptional regulation, signal transduction and cell-type-specific expression. PMID- 11217297 TI - Models for gain-of-function and loss-of-function of MMPs. Transgenic and gene targeted mice. PMID- 11217298 TI - Expression of MMPs and TIMPs in mammalian cells. PMID- 11217299 TI - Expression of recombinant matrix metalloproteinases in Escherichia coli. PMID- 11217300 TI - Expression of human collagenase I (MMP-1) and TIMP-1 in a baculovirus-based expression system. PMID- 11217301 TI - Expression of recombinant matrix metalloproteinases in yeast. PMID- 11217302 TI - Expression of recombinant membrane-type MMPs. PMID- 11217303 TI - Strategies for cloning new MMPs and TIMPs. PMID- 11217304 TI - Refolding of TIMP-2 from Escherichia coli inclusion bodies. PMID- 11217305 TI - Expression and refolding of full-length human TIMP-1. PMID- 11217306 TI - Purification of MMPs and TIMPs. PMID- 11217307 TI - Monitoring MMP and TIMP mRNA expression by RT-PCR. PMID- 11217308 TI - Measuring transcription of metalloproteinase genes. Nuclear run-off assay vs analysis of hnRNA. PMID- 11217309 TI - In situ hybridization for metalloproteinases and their inhibitors. PMID- 11217310 TI - Use of EIA to measure MMPs and TIMPs. PMID- 11217311 TI - Immunohistochemistry of MMPs and TIMPs. PMID- 11217312 TI - Detecting polymorphisms in MMP genes. PMID- 11217313 TI - Methods for studying activation of matrix metalloproteinases. PMID- 11217314 TI - Assay of matrix metalloproteinases against matrix substrates. PMID- 11217315 TI - Zymography and reverse zymography for detecting MMPs, and TIMPs. PMID- 11217316 TI - In situ zymography. PMID- 11217317 TI - Detection of focal proteolysis using Texas-red-gelatin. PMID- 11217318 TI - Antibodies to MMP-cleaved aggrecan. PMID- 11217319 TI - Structural studies on MMPs and TIMPs. PMID- 11217320 TI - Cartilage proteoglycan release assay. PMID- 11217321 TI - Immunoassay for collagenase-mediated cleavage of types I and II collagens. PMID- 11217322 TI - Collagen degradation assays. PMID- 11217323 TI - Invasion assays and matrix metalloproteinases. Quantification of cellular invasion using propidium iodide labeling and confocal laser scanning microscopy. PMID- 11217325 TI - Kinetic analysis of the inhibition of matrix metalloproteinases by tissue inhibitor of metalloproteinases (TIMP). PMID- 11217326 TI - Assaying growth factor activity of tissue inhibitors of metalloproteinases. PMID- 11217324 TI - Using fluorogenic peptide substrates to assay matrix metalloproteinases. PMID- 11217328 TI - Influence of polymer concentration and polymer composition on capillary electrophoresis of DNA. PMID- 11217327 TI - Matrix metalloproteinase substrate binding domains, modules and exosites. Overview and experimental strategies. PMID- 11217329 TI - Capillary coatings. Choices for capillary electrophoresis of DNA. PMID- 11217330 TI - Replaceable polymers for DNA sequencing by capillary electrophoresis. PMID- 11217331 TI - Sieving matrix selection. PMID- 11217332 TI - Parameters affecting capillary electrophoretic separation of DNA. PMID- 11217333 TI - DNA separation by capillary electrophoresis in lyotropic polymer liquid crystals. PMID- 11217334 TI - Capillary electrophoresis of DNA fragments using poly(ethylene oxide) as a sieving material. PMID- 11217335 TI - DNA capillary electrophoresis using block copolymer as a new separation medium. PMID- 11217336 TI - DNA analysis under highly denaturing conditions in bare fused silica capillaries. PMID- 11217337 TI - Capillary electrophoresis with glycerol as an additive. PMID- 11217338 TI - DNA separation mechanisms during electrophoresis. PMID- 11217339 TI - Capillary electrophoresis of DNA fragments with replaceable low-gelling agarose gels. PMID- 11217341 TI - The application of capillary electrophoresis for DNA polymorphism analysis. AB - CE fractions may also be collected and then subjected to additional analysis. Nanoliter fractions containing size or shape fractionated DNA fragments can be collected on moving affinity membranes (125) or into sample chambers (126). The exact timing of the collection steps is achieved by determining the velocity of each individual zone measured between two detection points near the end of the capillary. The DNA samples may subsequently be identified by probe hybridization, or by PCR-linked sequencing. Capillary fractions containing metabolites and derivatives of DNA and small DNA adducts can also be sampled, and then characterized directly by highly sensitive MALDI-TOF atomic analysis (112-118) and ESI-MS (118,119). The automation and integration of PCR and CE analysis (PCR CE) on a microchip (3-12,96) will also contribute greatly to its adoption as the analysis tool of choice. Significantly, these tools will be applied for DNA sequencing (75,108), for genome mapping (65) and genotyping (42-46), for improved certainty in disease detection (3-6,107,120) and for DNA mutation analysis (2 12,27,58). Recent improvements in the design CAE arrays and associated equipment such as the radial CAE microplate and rotary confocal signal detection system (127) overcome some of the detection limitations of linear CAE and microchip devices and allow the parallel genotyping of 96 samples in about 120 s. The integration of microreactive capillary surface assays (128) and "in-capillary" analysis will also lead to further increases in the speed and sensitivity of CE based analysis. The recent announcement of the completion of the first draft sequence of the 90% of the entire human genome within 6 mo by Celera Genomics by sequencing random DNA fragments using several hundred ABI 3700 machines (129) illustrates the enormous efficiency realized through the automation of DNA sequencing by CAE. Sequencing was performed at an average rate of approximately 6 x 10(9) bases/yr. The CAE machines will now be employed for a concerted resequencing of genome elements to create an extremely high-density polymorphism map of the entire genome (130). This map will be based principally on single nucleotide polymorphisms, and will catapult human medicine into a new era of closely detailed genetic trait mapping to identify the genetic basis of multi gene diseases. PMID- 11217342 TI - Pulsed-field capillary electrophoresis separation of large DNA fragments. PMID- 11217340 TI - Robust field inversion capillary electrophoretic separation of long DNA fragments. PMID- 11217343 TI - Collection of capillary electrophoresis fractions on a moving membrane. PMID- 11217345 TI - Quality control of nucleotides and primers for PCR. PMID- 11217346 TI - Analysis of modified oligonucleotides with capillary gel electrophoresis. PMID- 11217344 TI - Separation of supercoiled DNA using capillary electrophoresis. PMID- 11217347 TI - Use of capillary electrophoresis for concentration analysis of phosphorothioate oligonucleotides. PMID- 11217348 TI - Capillary electrophoresis separation of ribonucleosides. PMID- 11217349 TI - On-line preconcentration and separation of antisense oligonucleotides by ITP-CE in dextran-filled capillaries. PMID- 11217350 TI - Capillary electrophoresis-mass spectrometric analysis of DNA adducts. PMID- 11217351 TI - Analysis of environment-induced DNA damage by capillary electrophoresis. PMID- 11217352 TI - Assay for DNA damage using immunochemical recognition and capillary electrophoresis. PMID- 11217353 TI - Analysis of DNA damage using capillary zone electrophoresis and electrospray mass spectrometry. PMID- 11217354 TI - Purification methods for preparing polymerase chain reaction products for capillary electrophoresis analysis. PMID- 11217355 TI - Integration of phosphodiesterase-induced degradation of oligonucleotides with capillary polymer-sieving electrophoresis. PMID- 11217356 TI - Capillary electrophoresis of urinary normal and modified nucleosides of cancer patients. PMID- 11217357 TI - Analytical considerations for capillary electrophoresis. Quantitative measurements. PMID- 11217358 TI - Microchip-based capillary electrophoresis systems. PMID- 11217359 TI - DNA sequencing by capillary array electrophoresis. PMID- 11217360 TI - Determining dye-induced DNA mobility shifts for DNA sequencing fragments by capillary electrophoresis. PMID- 11217361 TI - Modulation of growth factor receptor expression by irradiation for immunotoxin targeting. PMID- 11217362 TI - Quantification of immunotoxin number for complete therapeutic response. PMID- 11217363 TI - In vitro studies of ricin A-chain-induced vascular leak syndrome. PMID- 11217364 TI - Immunotoxin treatment of brain tumors. PMID- 11217365 TI - Cytotoxins directed at interleukin-4 receptors as therapy for human brain tumors. PMID- 11217366 TI - CD7-specific single chain Fv immunotoxins. Design and expression. PMID- 11217367 TI - Bispecific monoclonal antibodies for the targeting of type I ribosome inactivating proteins against hematological malignancies. PMID- 11217368 TI - Tyrosine kinase inhibitors against EGF receptor-positive malignancies. PMID- 11217370 TI - Gene therapy with immunotoxins. PMID- 11217369 TI - Targeting tumor vasculature using VEGF-toxin conjugates. PMID- 11217371 TI - Effects of selective immunotoxic lesions on learning and memory. PMID- 11217372 TI - Targeting toxins to neural antigens and receptors. PMID- 11217373 TI - In vivo testing of anti-HIV immunotoxins. PMID- 11217374 TI - Development and activities of the BR96-doxorubicin immunoconjugate. PMID- 11217375 TI - Recombinant fusion toxins directed against the human granulocyte-macrophage colony stimulating factor (GM-CSF) receptor. PMID- 11217376 TI - Synthesis of monensin derivatives and their effect on the activity of ricin A chain immunotoxins. PMID- 11217377 TI - Purification and conjugation of type 1 ribosome-inactivating proteins. PMID- 11217378 TI - Comparison of immunotoxins bearing a single saporin molecule with multiple toxin conjugates. PMID- 11217379 TI - Propagation of wild-type and mutant SV40. PMID- 11217380 TI - Generation of recombinant SV40 vectors for gene transfer. PMID- 11217381 TI - Production of SV40 proteins in insect cells and in vitro packaging of virions and pseudovirions. PMID- 11217382 TI - Using retroviral vectors to express SV40 tumor antigens. PMID- 11217383 TI - Neoplastic transformation assays. PMID- 11217384 TI - Methods to assess inhibition of adipocyte differentiation by SV40 large T antigen. PMID- 11217386 TI - Propagation and assay of BK virus. PMID- 11217385 TI - SV40-mediated immortalization. PMID- 11217387 TI - Biology of p53 and SV40 large T association. PMID- 11217388 TI - Binding of SV40 large T antigen to the retinoblastoma susceptibility gene product and related proteins. PMID- 11217389 TI - In situ electroporation for the measurement of c-Ras activation by SVLT. PMID- 11217390 TI - Role of SV40 small t in cell lysis, transformation, and signaling. PMID- 11217391 TI - Cytotoxic T lymphocytes in SV40 infections. PMID- 11217392 TI - Detection of SV40 DNA sequences in human tissue. PMID- 11217393 TI - Guide to techniques in creating transgenic mouse models using SV40 T antigen. PMID- 11217395 TI - Methods for studying interactions between Simian virus 40 T-antigen and the viral origin of replication. PMID- 11217394 TI - Molecular methods for identification and genotyping of BK virus. PMID- 11217396 TI - Cell-free transcription of SV40. PMID- 11217397 TI - Quantitation and structural analysis of SV40 RNAs. PMID- 11217398 TI - Propagation and assay of the JC virus. PMID- 11217399 TI - Hantaviruses: history and overview. PMID- 11217400 TI - Clinical manifestations of New World hantaviruses. PMID- 11217401 TI - Clinical characteristics of hantavirus infections on the Eurasian continent. PMID- 11217402 TI - Replication of hantaviruses. PMID- 11217403 TI - Human immune response, host genetics, and severity of disease. PMID- 11217404 TI - Vaccines against hantaviruses. PMID- 11217405 TI - Hantavirus maturation. PMID- 11217406 TI - Virus evolution and genetic diversity of hantaviruses and their rodent hosts. PMID- 11217407 TI - Modeling hantavirus maintenance and transmission in rodent communities. PMID- 11217408 TI - Cellular receptors and hantavirus pathogenesis. AB - Hantaviruses cause two potentially lethal diseases, HPS and HFRS, and both diseases result in defects in vascular permeability and platelet function. Human beta 3 integrins confer cellular susceptibility to HPS- and HFRS-causing hantaviruses, a fact directly linking platelets, endothelial cells, and hantavirus diseases to the use of [figure: see text] cellular receptors that maintain capillary integrity and regulate platelet function. The role of vitronectin, PAI-1, uPAR, and complement cascades in hantavirus pathogenesis are unstudied but may contribute to specific disease syndromes effected by hantaviruses. The divergence of hantavirus surface glycoproteins and common beta 3-integrin usage provides further insight into the interaction of hantaviruses with cells. G1 and G2 glycoprotein variation is likely to contribute to additional interactions that determine pathogenic responses to individual viruses. beta 3-integrin usage also suggests that common elements exist on G1 or the more highly conserved G2 surface glycoprotein, which mediate viral attachment to integrins. Although there is currently no data defining the virion attachment protein, the development of antibodies that recognize the hantavirus attachment protein and block integrin interactions is of interest since it is likely to provide an additional point for therapeutic intervention and vaccine development. There are a plethora of effects that could be elicited by hantavirus regulation of cellular beta 3 integrins and their ligands that are consistent with hantavirus diseases. Since beta 3 integrins are critical adhesive receptors on platelets and endothelial cells and regulate both vascular permeability and platelet activation and adhesion, the use of these receptors by hantaviruses is likely to be fundamental to hantavirus pathogenesis. The lack of an animal model for hantavirus pathogenesis has prevented a systematic analysis of immune and cellular responses to hantavirus infections, and it impedes our ability to study protective or therapeutic approaches to hantavirus diseases. However, recent findings suggest that human beta 3 integrins within transgenic mice may provide animal models of hantavirus pathogenesis and have the potential to radically alter the ability to investigate hantavirus disease. PMID- 11217410 TI - Physiology, regulation, and limits of the synthesis of poly(3HB). AB - The properties of poly(3-hydroxybutyrate) combined with the fact that it can be produced easily by numerous prokaryotes from renewable resources and even from potentially toxic waste products using well-known fermentation processes have generated keen interest in this biopolyester as a substitute for chemo-synthetic petroleum-derived polymers in many applications. However, the high price of poly(3HB) compared with the conventional synthetic materials currently in use has restricted its availability in a wide range of applications. If the economic viability of poly(3HB) production and its competitiveness are to be improved, more must be found out about the phenotypic optimization and the upper limits of bacterial systems as the factory of poly(3HB). In this chapter, two aspects of poly(3HB) are reviewed--poly(3HB) formation as a physiological response to external limitations and overcoming internal bottlenecks, and poly(3HB) as a commercially attractive polyester. From a physiological viewpoint, the ability to synthesize and degrade poly(3HB) is considered an investment in the future and provides organisms with a selective advantage. Poly(3HB) is presented as a strategic survival polymer, and it is shown that growth-associated synthesis is not as rare as reported. The influence of the efficiency and velocity of cell multiplication and product formation, of poly(3HB) content and of productivity on the overall yield, and finally on the economics of the whole process are discussed and evaluated from the technological or consumer's point of view. The specific production rate and poly(3HB) content appear to be more important than the yield coefficients. PMID- 11217411 TI - Production of microbial polyesters: fermentation and downstream processes. AB - Poly(3-hydroxyalkanoates) (PHAs) constitute a large and versatile family of polyesters produced by various bacteria. PHAs are receiving considerable attention because of their potential as renewable and biodegradable plastics, and as a source of chiral synthons since the monomers are chiral. Industrial PHA production processes have been developed for poly(3-hydroxybutyrate) (poly(3HB)) and poly(3-hydroxybutyrate-co-3-valerate) (poly(3HB-co-3HV). More than 100 other poly(3HAMCL)s, characterized by monomers of medium chain length, have been identified in the past two decades. These monomers typically contain 6-14 carbon atoms, are usually linked via-3-hydroxy ester linkages, but can occasionally also exhibit 2-, 4-, 5-, or 6-hydroxy ester linkages. Such polyesters are collectively referred to as medium chain length PHAs poly(3HAMCL)s. The vast majority of these interesting biopolyesters have been studied and produced only on the laboratory scale. However, there have been several attempts to develop pilot scale processes, and these provide some insight into the production economics of poly(3HAMCL)s other than poly(3HB) and poly(3HB-co-3HV). These processes utilize diverse fermentation strategies to control the monomer composition of the polymer, enabling the tailoring of polymer material properties to some extent. The best studied of these is poly(3-hydroxyoctanoate) (poly(3HO)), which contains about 90% 3-hydroxyoctanoate. This biopolyester has been produced on the pilot scale and is now being used in several experimental applications. PMID- 11217409 TI - Polyesters in higher plants. AB - Polyesters occur in higher plants as the structural component of the cuticle that covers the aerial parts of plants. This insoluble polymer, called cutin, attached to the epidermal cell walls is composed of interesterified hydroxy and hydroxy epoxy fatty acids. The most common chief monomers are 10,16-dihydroxy C16 acid, 18-hydroxy-9,10 epoxy C18 acid, and 9,10,18-trihydroxy C18 acid. These monomers are produced in the epidermal cells by omega hydroxylation, in-chain hydroxylation, epoxidation catalyzed by P450-type mixed function oxidase, and epoxide hydration. The monomer acyl groups are transferred to hydroxyl groups in the growing polymer at the extracellular location. The other type of polyester found in the plants is suberin, a polymeric material deposited in the cell walls of a layer or two of cells when a plant needs to erect a barrier as a result of physical or biological stress from the environment, or during development. Suberin is composed of aromatic domains derived from cinnamic acid, and aliphatic polyester domains derived from C16 and C18 cellular fatty acids and their elongation products. The polyesters can be hydrolyzed by pancreatic lipase and cutinase, a polyesterase produced by bacteria and fungi. Catalysis by cutinase involves the active serine catalytic triad. The major function of the polyester in plants is as a protective barrier against physical, chemical, and biological factors in the environment, including pathogens. Transcriptional regulation of cutinase gene in fungal pathogens is being elucidated at a molecular level. The polyesters present in agricultural waste may be used to produce high value polymers, and genetic engineering might be used to produce large quantities of such polymers in plants. PMID- 11217412 TI - Production of microbial polyester by fermentation of recombinant microorganisms. AB - Polyhydroxyalkanoates (PHAs) can be produced from renewable sources and are biodegradable with similar material properties and processibility to conventional plastic materials. With recent advances in our understanding of the biochemistry and genetics of PHA biosynthesis and cloning of the PHA biosynthesis genes from a number of different bacteria, many different recombinant bacteria have been developed to improve PHA production for commercial applications. For enhancing PHA synthetic capacity, homologous or heterologous expression of the PHA biosynthetic enzymes has been attempted. Several genes that allow utilization of various substrates were transformed into PHA producers, or non-PHA producers utilizing inexpensive carbon substrate were transformed with the PHA biosynthesis genes. Novel PHAs have been synthesized by introducing a new PHA biosynthesis pathway or a new PHA synthase gene. In this article, recent advances in the production of PHA by recombinant bacteria are described. PMID- 11217413 TI - Production of polyesters in transgenic plants. AB - Polyhydroxyalkanoates (PHAs) are bacterial polyesters having the properties of biodegradable thermoplastics and elastomers. Synthesis of PHAs has been demonstrated in transgenic plants. Both polyhydroxybutyrate and the co-polymer poly(hydroxybutyrate-co-hydroxyvalerate) have been synthesized in the plastids of Arabidopsis thaliana and Brassica napus. Furthermore, a range of medium-chain length PHAs has also been produced in plant peroxisomes. Development of agricultural crops to produce PHA on a large scale and at low cost will be a challenging task requiring a coordinated and stable expression of several genes. Novel extraction methods designed to maximize the use of harvested plants for PHA, oil, carbohydrate, and feed production will be needed. In addition to their use as plastics, PHAs can also be used to modify fiber properties in plants such as cotton. Furthermore, PHA can be exploited as a novel tool to study the carbon flux through various metabolic pathways, such as the fatty acid beta-oxidation cycle. PMID- 11217414 TI - In vitro biosynthesis of polyesters. AB - In vitro synthesis of polyesters using isolated enzymes as catalyst via non biosynthetic pathways is reviewed. In most cases, lipase was used as catalyst and various monomer combinations, typically oxyacids or their esters, dicarboxylic acids or their derivatives/glycols, and lactones, afforded the polyesters. The enzymatic polymerization often proceeded under mild reaction conditions in comparison with chemical processes. By utilizing characteristic properties of lipases, regio- and enantioselective polymerizations proceeded to give functional polymers, most of which are difficult to synthesize by conventional methodologies. PMID- 11217415 TI - Properties, modifications and applications of biopolyesters. AB - Poly(hydroxyalkanoates) (PHAs), of which poly(hydroxybutyrate) (PHB) is the most common, can be accumulated by a large number of bacteria as energy and carbon reserve. Due to their biodegradability and biocompatibility these optically active biopolyesters may find industrial applications. A general overview of the physical and material properties of PHAs, alongside with accomplished applications and new developments in this field is presented in this chapter. The properties of PHAs are dependent on their monomer composition and therefore it is of great interest that recent research has revealed that, in addition to PHB, a large variety of PHAs can be synthesized microbially. The monomer composition of PHAs depends on the nature of the carbon source and microorganism used. PHB is a typical highly crystalline thermoplastic whereas medium chain length PHAs are elastomers with low melting points and a relatively lower degree of crystallinity. By (chemical) modification of the PHAs, the ultimate properties of the materials can be adjusted even further, when necessary. Applications that have been developed from PHB and related materials (e.g. Biopol) can be found in very different application areas and cover packaging, hygienic, agricultural and biomedical products. Recent application developments based on medium chain length PHAs range from high solid alkyd-like paints to pressure sensitive adhesives, biodegradable cheese coatings and biodegradable rubbers. Technically, the prospects for PHAs are very promising. When the price of these materials can be further reduced, application of biopolyesters will also become economically very attractive. PMID- 11217416 TI - Microbial degradation of polyesters. AB - Polyesters, such as microbially produced poly[(R)-3-hydroxybutyric acid] [poly(3HB)], other poly[(R)-hydroxyalkanoic acids] [poly(HA)] and related biosynthetic or chemosynthetic polyesters are a class of polymers that have potential applications as thermoplastic elastomers. In contrast to poly(ethylene) and similar polymers with saturated, non-functionalized carbon backbones, poly(HA) can be biodegraded to water, methane, and/or carbon dioxide. This review provides an overview of the microbiology, biochemistry and molecular biology of poly(HA) biodegradation. In particular, the properties of extracellular and intracellular poly(HA) hydrolyzing enzymes [poly(HA) depolymerases] are described. PMID- 11217417 TI - Polyesters from microorganisms. AB - Bacterial polyesters have been found to have useful properties for applications as thermoplastics, elastomers, and adhesives and are biodegradable and biocompatible. Poly(3-hydroxyalkanoates) (PHAs) and poly(beta-malate) are the most representative polyesters synthesized by microorganisms. PHAs containing a wide variety of repeating units can be produced by bacteria, including those containing many types of pendant functional groups which can be synthesized by microorganisms that are grown on unnatural organic substrates. Poly(beta-malate) is of interest primarily for medical applications, especially for drug delivery systems. In this chapter, the bacterial production and properties of poly(3 hydroxyalkanoates) and poly(beta-malate) are described with emphasis on the former. PMID- 11217419 TI - The history and biology of Marek's disease virus. PMID- 11217418 TI - Biochemical and molecular basis of microbial synthesis of polyhydroxyalkanoates in microorganisms. AB - Intensive research on the physiology, biochemistry, and molecular genetics of the metabolism of polyhydroxyalkanoates (PHA) during the last 15 years has revealed a dramatic increase of our knowledge on the biosynthesis of these polyesters in bacteria. This mainly very basic research has revealed several new, hitherto not described enzymes and pathways. In addition, many genes encoding the enzymes of these pathways and in particular the key enzyme of PHA biosynthesis, PHA synthase, were cloned and characterized at a molecular level. This knowledge was utilized to establish PHA biosynthesis in many prokaryotic and eukaryotic organisms, which were unable to synthesize PHAs, and to apply the methodology of metabolic engineering, thus opening new perspectives for the production of various PHAs by fermentation biotechnology or agriculture in economically feasible processes. This contribution summarizes the properties of PHA synthases and gives an overview on the genes for these enzymes and other enzymes of PHA biosynthesis that have been cloned and are available. It also summarizes our current knowledge on the regulation at the enzyme and gene level of PHA biosynthesis in bacteria. PMID- 11217420 TI - Genetic resistance to Marek's disease. PMID- 11217421 TI - The genomic structure of Marek's disease virus. PMID- 11217422 TI - Protein-coding content of the sequence of Marek's disease virus serotype 1. PMID- 11217423 TI - A complete genomic DNA sequence of Marek's disease virus type 2, strain HPRS24. PMID- 11217424 TI - Marek's disease virus latency. AB - MDV latency is defined as the persistence of the viral genome in the absence of production of infectious virus except during reactivation. A number of systems for studying MDV latency exist, and most involve the use of lymphoblastoid cells or tumors. It has been difficult to divorce latency and transformation. Understanding the relationship between these two states remains a major challenge for the MDV system. Based on their patterns of expression, the MDV LATs are apt to be important in the balance between latent and lytic infections. The LATs are a complex group of transcripts. The profile of gene expression that characterizes latency differs among all herpesviruses, and MDV is no exception. MDV LATs bear little resemblance to LATs of other alphaherpesviruses or to the LATs of other lymphotropic herpesviruses. LAT splicing patterns are complex and the relationships among various spliced species or between these species and the large 10-kb transcript are unknown. In addition, the existence of any protein gene products of significance is unknown at this time. More work is needed to further investigate the significance and function of these RNAs. Better technology to construct mutants in the MDV system is badly needed, since the analysis of mutants in the chicken is a powerful and unique advantage of the MDV system. PMID- 11217425 TI - Meq: an MDV-specific bZIP transactivator with transforming properties. PMID- 11217426 TI - Pathogenesis of Marek's disease virus infection. PMID- 11217427 TI - Polyvalent recombinant Marek's disease virus vaccine against poultry diseases. PMID- 11217428 TI - Protective efficacy of Marek's disease vaccines. PMID- 11217430 TI - [Differential diagnosis of primary lung tumors and pulmonary metastases]. AB - The lungs are frequent metastatic targets for metastases of extrapulmonary cancer with or without known primary tumor. Metastases of extrapulmonary tumors are found in 20 to 50%. Metastatic carcinoma of unknown primary localizations contributes to about 4% of all diagnosed carcinomas. Within this group adenocarcinomas can be found in 60%, squamous cell carcinomas in 15%, unspecified tumors including small cell and undifferentiated tumors in 25% histogenetically. Due to overlapping histologic features a histopathological distinction of primary and secondary tumors might be difficult. Topography, size and form of pulmonary growth pattern are important aspects for the differential diagnosis. Primary lung tumors are mainly localized in upper lobes as singular nodules, metastases in lower lobes as multiple lesions. For the distinction of endobronchial primary or secondary squamous cell carcinomas findings of severe dysplasia and CIS of the bronchial epithelium are important. Stroma and vascularisation pattern of primary and secondary lung tumors differ in distribution, arrangement and extracellular matrix components. Pulmonary vascular changes in primary tumors are characterized by vascular infiltration, destruction and occlusion whereas in secondary tumors intravascular embolisation and extravasation predominate. Immunohistochemical techniques using different algorithms of antibodies (cyto-keratins, neuroendocrine markers, TTF-1, vimentin, HMB 45, LCA, oncogenes, tumor suppressor genes etc.) give vital clues as to the origin of the primary tumor. Metastases of thyroid or prostate carcinomas, melanomas, sarcomas, lymphomas etc. can be reliably differentiated. Molecular investigations are up to now only subject in research. PMID- 11217429 TI - Immune responses to Marek's disease virus infection. PMID- 11217431 TI - [Differential diagnosis and etiology of epitheloid cell granulomatosis of the lung]. AB - Our knowledge on epithelioid cell granulomatosis of the lung has been extended in recent years. New entities have been added, like zirconiosis, others like tuberculosis, mycobacteriosis and sarcoidosis have gained new interest, because molecular techniques allowed new insight into their pathogenesis and a more rapid and species-specific diagnosis. Experimental work in addition has added a lot of information about the network of cytokines and other inflammatory mediators responsible for granuloma formation, however, our knowledge of this network is still incomplete. Three types of agents are now known to cause epitheloid cell granulomas: infectious organisms (bacteria, fungi, and parasites), products of plants and animals (pollen, sporangia, proteins), and metallic compounds. In addition there is still a group of epithelioid cell granulomatoses with unknown etiology. Sarcoidosis, one of these granulomatosis, has recently elicited an old controversy: By molecular techniques Mycobacteria and Corynebacterium acnes have been identified in sarcoid granulomas and a link to the aetiology of sarcoidosis has been proposed. If these bacteria induce some cases of sarcoidosis by an allergic mechanism, has still to be proven. PMID- 11217432 TI - [Value of bronchoalvoeolar lavage in the diagnosis of lung disease]. AB - Bronchoalveolar lavage (BAL) is an important tool for evaluating interstitial lung diseases. It provides information on inflammatory cells which play an important role in the pathogenesis of such diseases and complements the information of the lung biopsy. The method is based on the observation, that the cells recovered by BAL reflect the population of cells in pulmonary parenchyma. In healthy subjects the main cells in the lavage fluid are macrophages (> or = 80%), lymphocytes (10-20%), some few neutrophils (< or = 4%), eosinophils (< or = 3%) and single mast cells. There are significant differences in the distribution of cell types in never-smokers, exsmokers and current smokers. Generally the increase in the number of lymphocytes is a hallmark of granulomatous and allergic lung diseases. Evaluation of the lymphocyte surface antigen phenotypos allows the recognition of sarcoidosis (increased proportion of T-helper lymphozytes) and extrinsic allergic alveolitis (increased proportion of T-suppressor lymphocytes). High neutrophil counts are characteristic of fibrosing processes or of occupational diseases caused by inhalation of inorganic dust. The evaluation of the diagnostic accuracy of the BAL is difficult because the final diagnosis of many symptomatically cured patients is not clear. Nevertheless, the evaluation of our cases showed a surprisingly high overall diagnostic accuracy (> 80%). However, the accuracy of negative diagnosis (exclusion of a certain disease) is slightly higher than this of the positive ones (diagnosis confirmed). PMID- 11217433 TI - [Tumorigenesis after intra-portal pancreatic islet transplantation in diabetic rats]. AB - In a novel model of hepatocarcinogenesis, a low number of isologous pancreatic islets were transplanted via the portal veins into the livers of streptozotocin diabetic rats. The number of islets is chosen so low, that the diabetic state is only ameliorated by the islet transplantation. The permanent high blood glucose stimulates the beta-cells of the islet transplants to permanent maximal synthesis and secretion of insulin which causes hyper-insulinemia in the liver acini downstream of the transplants. The hepatocytes of these acini show alterations which are typical for insulin effects but also for glycogen storing foci of altered hepatocytes induced by different protocols of experimental hepatocarcinogenesis in different species, and which are also found in human preneoplastic liver foci. Indeed, the altered hepatocytes after low-number islet transplantation proceeded in long-term experiments to hepatocellular adenomas and hepatocellular carcinomas. Hyperplasia of islet cells developed in the transplanted islets, as a consequence of hyperglycemia which for the beta cells is not only a secretory, but also a proliferative stimulus. Six out of 33 animals between the 18th and the 24th month after islet transplantation changed from hyperglycemia to severe hypoglycemia, due to insulinomas which had developed in the liver from the transplanted islets. Development of hepatocellular tumors as well as insulinomas start in this model with alterations, which have been shown to be of preneoplastic nature. They can be understood as local pathological adaptative phenomena without the postulate of a primary genetic damage. PMID- 11217434 TI - [Monocytic B-cells represent a new cell population that is mainly recruited from unmutated polyconal naive B-cells]. AB - Monocytoid B-cells appear as a distinct B-cell population in a number of lymphadenopathies but above all in Piringer's lymphadenopathy. Up until now, their assignment to a recognised B-cell subpopulation has not been conclusively achieved. Immunohistological studies have shown characteristics in common with the tumour cells of hairy cell leukemia and also with so-called splenic marginal zone cells. In order to unequivocally clarify their B-cell differentiation stage we have isolated single monocytoid B-cells from immunostained frozen sections and have analysed their immunoglobulin chain gene rearrangements. In addition we have studied the Ig-expression of monocytoid B-cells at both the RNA and protein levels. PMID- 11217435 TI - [Genetic and biological features define two types of follicular non-Hodgkin grade 3 lymphoma]. AB - In the REAL classification system, follicular lymphomas (FL) were subdivided into three grades depending on the number of blasts (6). In this study, we were interested in defining biological parameters possibly being important in the delineation of subgroups. Between 1990 and 1998, biological and cytogenetic investigations were performed on 91 FL. Clonal aberrations were found in all cases. The tumours were subclassified according to the blast content and the morphology of the centrocytes into 29 FL 1, 33 FL 2, 15 FL 3, and 14 FL 3 with a diffuse large B-cell lymphoma component (FL 3 + DLBL). They were characterised by classical cytogenetics, for their mitotic (MI) and proliferative (PI) indices, and CD10, bcl-2, and p53-expression. In contrast to FL 1 and FL 2, which showed a common genetic background with t(14;18), and only differed by their blast content and MI/PI, FL 3 (with or without associated DLBL) turned out to be an inhomogeneous group. 11 follicular lymphomas (with > 150 blasts/10HPF) still showed maturation to centrocytes. They were positive for CD10 and harboured the t(14;18) in 73%. These cases correspond to a "high grade" variant of centroblastic-centrocytic lymphoma according to the Kiel classification (FL 3a). In 18 cases with a follicular or follicular and diffuse growth pattern, the infiltrate consisted of centroblasts exclusively. These tumours were CD10+ in only 50% and were t(14;18)+ in only 22%. Secretory differentiation (clg+) was found in 44%. They were--with respect to primary and secondary chromosome aberrations--more comparable to a follicular variant of DLBL and hence, correspond to centroblastic lymphoma, follicular or centroblastic lymphoma, follicular and diffuse according to the Kiel classification (FL 3b). By histomorphological, biological and cytogenetic investigations, therefore, FL 3 can be delineated into two different biological subgroups with obviously different transformation pathways. PMID- 11217436 TI - [Analysis of clonality of nephroblastomas in patients with Wilms tumors]. PMID- 11217437 TI - [Morphologic response evaluation of neoadjuvant chemotherapy of gastric carcinoma]. AB - A primary goal of the histopathologic evaluation of the gastric resection specimen is the determination of prognostically relevant factors, but it is not known whether, following neoadjuvant therapy, these factors have the same influence on prognosis. The goal of this study was to investigate prognostically relevant macroscopic and microscopic findings after neoadjuvant chemotherapy. The resection specimens of 36 patients with locally advanced gastric carcinoma who had been treated with Etoposide, Adriamycin and Cisplatin were investigated with respect to tumor size, Lauren type, ypTNM, UICC R-status, lymphangiosis, and degree of regression. On the basis of these factors, a prognosis score was developed that included both the degree of regression (grade 1-3), staging parameters (UICC T-category, R-status), tumor size and lymphatic vessel invasion. All of the parameters were weighted according to a score (1 point--best, 3 points -worst). The points were added for each individual case and the cases were divided into three prognosis groups, Group A: 5-7 points (n = 5), Group B: 8-10 points (n = 15), and Group C: > or = 11 points (n = 16). When compared with survival by the Kaplan-Meier method, these three prognosis groups showed highly significant differences (p < 0.0001). These results demonstrate that it is possible to accurately predict survival using resection specimens following neoadjuvant chemotherapy, which could lead to the identification of subgroups for which additional, further adjuvant therapy might be useful. PMID- 11217438 TI - [beta-Catenin induces invasive growth by activating matrix metalloproteinases in colorectal carcinoma]. AB - beta-catenin was shown to be a major oncoprotein in colon cancer development. Its oncogenic function as a transcriptional activator is upregulated by mutations in the APC tumor suppressor gene, leading to a constitutive activation of the proliferation-associated genes c-myc and cyclin D. The aim of this study was to demonstrate a role of APC-mutations and dysregulated beta-catenin also for the progression of colorectal cancer, by identifying new target genes of beta-catenin associated with tumor invasion and metastasis. Potential invasion genes regulated by beta-catenin and its DNA binding partner TCF4 were identified by a computer search for the consensus DNA binding sequence in relevant promoter regions. Specific DNA binding was confirmed by gel shift assays. Functional importance of beta-catenin for the activation of identified genes was determined by luciferase reporter assays. The significance was demonstrated by coexpression of nuclear beta-catenin and the identified target genes by immunohistochemistry. Among other invasion genes, we identified the matrix metallo proteinases MMP-7 and MMP-1 activated by beta-catenin in the tumor cells. MMP-7 is an important factor for invasion and metastasis and overexpressed in 75% of colon carcinomas. The significance for human colon cancer development was demonstrated by a correlated overexpression of beta-catenin and the MMPs, beginning in large, severely dysplastic adenomas. Our results explain the high percentage of MMP-7 overexpression in colorectal tumors and the resulting activation of invasive growth. Moreover by identifying dysregulated beta-catenin as a transcriptional activator of MMPs and other invasion factors, we demonstrated an important role of mutated APC not only for early steps but also for the progression of colorectal carcinogenesis. PMID- 11217439 TI - [beta-Catenine as a genomic target of high-grade microsatellite instability in colorectal cancer]. AB - AIMS: Various inherited and acquired alterations affecting the genes and gene products of the WNT pathway appear to be involved in the different molecular routes leading to colorectal cancer (CRC). This study was initiated to investigate the prevalence of somatic mutations in the beta-catenin gene (CTNNB1) and the associated pathology in CRC with defective DNA mismatch repair. METHODS: Paraffin and/or frozen sections of 33 primary CRC (including any liver and lymph node metastases present) with high-grade microsatellite instability (MSI-H; i.e. with > or = 5 unstable microsatellite markers of 10 tested) were polytopically fractionated by microdissection. Genomic and c-DNA samples were sequenced across exons 2-4 of CTNNB1 and the expression patterns of beta-catenin (beta-C) analyzed by immunohistology and Western blotting. RESULTS: Seven somatic mutations affecting phosphorylation sites of exon 3 (2 deletions also encompassing parts of either intron 2 or exon 4 [delta X2/3 bzw. delta X3/4] and 5 missense mutations [2 x T41A, 2 x S45F, S45P]) were identified. Two mutations (delta X3/4 and S45F) were concordantly present in CRC primaries and their respective metastases whereas the S45P mutation was restricted to a hepatic metastasis. In the delta X2/3 CRC primary only a shortened 66 kD CTNNB1 gene product was present while its associated liver metastasis showed a total loss of beta-C expression. CONCLUSIONS: Both exon 3 and the entire locus coding for beta-C are somatically altered in approximately 20% of CRC with MSI-H at different stages of tumor progression. Thus CTNNB1 appears to be a genomic target for complex oncogenic mutations and deletional processes in a substantial fraction of this molecular subset of CRC. PMID- 11217440 TI - [New immunotherapeutic approaches for the treatment of anaplastic large cell lymphoma in a mouse model]. AB - As there is still a high mortality of the large cell anaplastic non Hodgkin lymphoma (ALCL) (between 40-70%, depending on prognostic factors) there is a need for new therapeutic approaches. Therefore, we studied different strategies for cancer immunotherapy in an immunogenic ALCL tumor model system: A murine IL-9 dependent T cell line was transfected with IL-9 cDNA, resulting in an autonomous growing T cell line designated G6BB, which had a high tumor incidence after injecting of as few as 10(4) cells subcutaneously into syngeneic C57Bl/6 mice. Tumor growth, dissemination, histology, and immunohistochemistry were similar to human ALCL. This mouse model provides an immunogenic in vivo system to investigate antitumor immunotherapies. In order to increase antigen recognition by T cells and T cell activation, we administered tumor bearing mice cell-based cancer vaccines with irradiated tumor cells alone or in combination with immunostimulating CpG-Oligonucleotides, a combination of Th1 cytokines and Th2 cytokine antibodies (IL-12, IFN-gamma, GM-CSF, Anti-IL-10) (after detecting a Th2 cytokine profile in G6BB), or the recall antigens diphtheria, pertussis, and tetanus. PMID- 11217441 TI - [CD143 expression in testicular germ cell tumors]. AB - CD143 (angiotensin I-converting enzyme) occurs in two isoforms: a testicular form (tCD143) expressed during spermatogenesis, and a somatic form (sCD143) generally found in certain other cell types. To study these isoforms in normal and neoplastic germ cells of humans, we analyzed a broad collective of different testicular germ cell tumors (GCTs) of adults, adjacent intratubular germ cell neoplasms (IGCNs), and testicular tissues representing the regular germ cell development. Different techniques were employed on fresh frozen and formalin fixed, paraffin-embedded tissues: CD143-mRNAs were analyzed by RT-PCR on selected cells after UV-laser-assisted cell picking and by in-situ hybridization using cRNA probes; the proteins were analyzed by semi-quantitative immunohistochemistry using monoclonal antibodies to CD143, and to PLAP/GCAP as controls. In contrast to normal germ cells bearing only tCD143 during spermiogenesis, both mRNA and protein of sCD143 were detected in neoplastic cells of all IGCNs and in the majority of seminomas. sCD143 expression also was found during testicular development, but was differently regulated in fetal germ cells and in GCTs compared with PLAP/GCAP. Thus, our findings (i) demonstrate profound changes in the expression of both CD143 isoforms during regular germ cell development and maturation, (ii) suspect sCD143 being involved in the regulation of germinal stem cell proliferation, (iii) are in agreement with the concept of an 'embryonic state' of neoplastic germ cells, (iv) indicate a close molecular relationship between IGCN and seminoma and, finally, (v) suggest sCD143 as an appropriate marker in the diagnosis of seminomas in addition to PIAP/GCAP. PMID- 11217442 TI - [Rudolf Virchow Prize 2000 from the German Society of Pathology]. PMID- 11217444 TI - [List of members]. PMID- 11217443 TI - Tumor patterning: analogies of neoplastic morphogenesis with embryogenesis. AB - Patterning or pattern formation is a spatial and temporal process, by which ordered arrangements of cells and tissue structure are attained. The term is mostly applied to the morphogenesis in developmental biology, but it can also be useful for the neomorphogenesis in tumor biology. Despite increasing data on the proliferation and differentiation of tumor cells, processes of tumor patterning are rarely studied and poorly understood. A fundamental embryonic process of patterning is the gastrulation and a basic example of neoplastic patterning is the colonic adenoma-carcinoma sequence. Both processes exhibit distinct nuclear translocations and expressions of beta-catenin, which is considered to be a decisive transcriptional regulator. Our recent studies demonstrate striking analogies of patterning and nuclear beta-catenin expressions between the colonic adenoma-carcinoma sequence and the gastrulation steps. The shared patterns are dissociation, reassembly, tubular reconstruction and branching of neoplastic cells in association with nuclear beta-catenin expressions. These new findings establish patterning as a relevant concept for tumor biology and link the neoplastic morphogenesis with embryogenesis. PMID- 11217446 TI - Tumor cell-matrix interaction: pericellular matrix degradation and metastasis. AB - In order to determine key MMPs for invasion and metastasis in various human cancers, we examined the expression of ten MMPs (MMP-1, 2, 3, 7, 8, 9, 13 and MT1, 2, 3-MMPs) and tissue inhibitors of metalloproteinases (TIMP-1 and 2) in breast carcinomas, thyroid papillary carcinomas, endometrial carcinomas, ovarian carcinomas, gastric adenocarcinomas, oral squamous cell carcinomas and gliomas. Of the MMPs examined, the activation of proMMP-2 by MT1-MMP (membrane type 1-MMP) was commonly important for the invasion and metastasis of these cancers except for endometrial carcinomas. The MMP-2 and MT1-MMP were localized to the carcinoma cells and gelatinolytic activity was demonstrated within the carcinoma cell nests by in situ zymography. In endometrial carcinomas, production and activation of proMMP-7 were a key determinant of the lymph node metastasis. The activation of proMMP-2 in gliomas involved MT2-MMP as well as MT1-MMP, and a combination of decreased TIMP-2 production and enhanced MT1-MMP expression was important in the subarachnoidal dissemination of glioblastoma cells. Brevican, a major adult brain proteoglycan, was degraded with MMP-1, 2, 3, 7, 10 and ADAMTS4 (aggrecanase-1) by being cleaved at the MMP site (the Ala360-Phe361 bond) with the MMPs and ADAM site (the Glu395-Ser396 bond) with ADAMTS4. Since activated MMP-2 and ADAMTS4 are present in human glioma tissues, they may play a key role in the invasion of glioma cells through the brevican degradation. The data in the present study suggest that the extracellular matrix-degrading metalloproteinases acting probably on the cell membranes of cancer cells are essential to the invasion and metastasis of human cancers. PMID- 11217445 TI - Molecular aspects of adhesion-epigenetic mechanisms for inactivation of the E Cadherin-mediated cell adhesion system in cancers. AB - E-Cadherin and its undercoat proteins, alpha- and beta-Catenins, which connect cadherins to actin filaments and establish firm cell-cell adhesion, act as an invasion suppressor system. It was demonstrated that transcriptional inactivation of E-Cadherin expression occurred frequently in tumor progression, and that E Cadherin expression in human cancer cells was regulated by CpG methylation around the promoter region. In diffusely infiltrating cancers, mutations were found in the genes for E-Cadherin and alpha- and beta-Catenins. The E-Cadherin-mediated cell-adhesion system is inactivated by tyrosine phosphorylation of beta-Catenin at the invading front of cancers with high metastatic ability. An attempt was made to identify the kinases that participate in the aberrant tyrosine phosphorylation, and c-erbB-2 protein was found to be directly associated with beta-Catenin. Transfection of N-terminally deleted beta-Catenin, which binds to c erbB-2 but not to cadherin, markedly reduced peritoneal dissemination and hematogenous metastasis of gastrointestinal cancer cells in mouse inoculation models. Regulation of the E-Cadherin-mediated cell adhesion system by tyrosine phosphorylation of beta-Catenin is important in determining the biological properties of human cancers. Tumor cells are dissociated throughout the entire tumor masses of diffuse-type cancers, whereas those of solid tumors with high metastatic potentials are often focally dissociated or dedifferentiated at the invading fronts. Thus, both irreversible and reversible mechanisms for inactivating the E-Cadherin-mediated cell adhesion system well correspond to the pathological features of human cancers. PMID- 11217447 TI - [Opening address of the President. Molecular patholgy: challenge, risks and chance]. PMID- 11217448 TI - Molecular aspects of invasion and metastasis of stomach cancer. AB - The scenario of multiple genetic and epigenetic alterations found in gastric carcinoma differs depending upon the two histological types, indicating that well differentiated or intestinal type and poorly differentiated or diffuse type gastric carcinomas have different genetic pathways. Cancer-stromal interaction through growth factor/cytokine receptor system which plays a central role in invasion and metastasis, is also different between the two types of stomach cancer. The majority of gastric carcinoma exhibit co-expression of IL-8 and its two receptors that evidently confer tumor angiogenesis. IL-8 increases the expression of EGF receptor, VEGF and IL-8 itself by tumor cells themselves, whereas IL-8 decreases expression of E-Cadherin, associated with increase in expression and activity of MMP-9 by tumor cells. These findings overall suggest that IL-8 produced by gastric cancer cells is used for sustained angiogenesis and tissue invasion and metastasis via autocrine/paracrine manners. On the other hand, co-expression of osteopontin (OPN) and CD44v9 in tumor cells correlates well with the degree of lyiphatic vessel invasion or long distant lymph node metastasis in diffuse type gastric carcinoma, indicating that mutual interaction between OPN and CD44v9 on the tumor cells is implicated in lymphogenous metastasis. In addition to these factors, tumor invasion and metastasis requires telomere maintenance regulated by telomerase activity. The human telomerase catalytic subunit, hTERT, is strongly expressed in almost all primary tumors and nodal metastasis. PMID- 11217449 TI - [Forms and nomenclature of gastrointestinal epithelial expansion: what is invasion?]. AB - In the gastrointestinal (GI) glandular mucosa, the term invasion is ill defined until today. In order to standardize the nomenclature of the expansion of benign and early malignant tumors of the glandular epithelium, we tried to establish a new descriptive terminology: In adenomas, the first glands with neoplastic epithelium may be divided by gland fission before there is primary superficial lateral expansion, followed by luminal expansion in form of budding, glandular fission and minimal branching, and a secondary downward vertical intra- and intertubular expansion into the mucosa. The different growth types of GI adenomas differ in the proportion of these components which will be considered below. In contrast, mucosal carcinomas usually do not show superficial lateral expansion, but they are usually characterized by a primary midmucosal disorderly lateral intertubular expansion with irregular branching and fusion of neoplastic glands, with undermining of the surface epithelium, and with compression and destruction of neighbouring glands by lateral and downward expansion of the neoplastic epithelium, finally with secondary erosions. This pattern of lateral intertubular expansion is indicative for carcinomatous invasion in GI mucosal carcinomas. The permeation of basal membranes usually does not occur in well differentiated carcinomas, which form new basal membranes. With increasing loss of differentiation, there is tumor cell dissociation with permeation or no production of basal membranes up to the pure diffuse type carcinoma; this process of invasion across basal membranes is merely one, but not the only sign of invasion, in our view. A fibrous stromal reaction usually does not occur in the mucosa, but it is most intense in the submucosa and subserosa, and much less pronounced in the muscularis propria. This fibrous stromal reaction is also indicative for invasion. However, Japanese pathologists do not diagnose malignancy only from architectural signs of invasion but mainly from cytological criteria, which also have to be considered aside from structural criteria given above. In comparison, epithelial growth in metaplastic processes is restricted to intratubular expansion or glandular fission without superficial lateral expansion. Pseudoinvasions of cohesive and diffuse types have to be considered for differential diagnosis. PMID- 11217450 TI - [Morphology and biology of invasion with Barret's carcinoma as an example]. AB - In order to determine the molecular genetic alterations associated with tumor invasion, Barrett's adenocarcinoma and its non-invasive precursor lesions were investigated by comparative genomic hybridization (CGH), fluorescence in situ hybridization (FISH), and loss of heterozygosity (LOH). Along the metaplasia dysplasia-carcinoma sequence in Barrett's adenocarcinoma gains on 7q, 8q, 20q, 2p, 10q and 17q, and losses on Y, 4q, 5q, 9p 18q and 14q became steadily more frequent. FISH demonstrated increasing DNA copy of numbers of c-erbB-2, 20q13.2 (AIB), c-myc and cyclin D1 during the development of Barrett's adenocarcinoma, and LOH confirmed DNA losses on 5q21 (APC) and 18q (DCC). Some of the chromosomal changes of the non-invasive precursor lesions were significantly different from the alterations detected in invasive carcinoma. Although molecular pathology may be used as diagnostic adjunct in future, the histopathological determination of invasion remains the most important diagnostic criterion of malignancy in Barrett's adenocarcinoma. PMID- 11217451 TI - [Cellular proteases and invasion]. AB - Cellular proteases are those proteases that are localized in the cytoplasm and on the cell surface, but not those secreted into the extracellular matrix. Proteases localized on the cell surface play a specific role in the invasion process of malignant tumor cells. These are activated by a relatively complicated cascade in which different cathepsins, the plasminogen activator system, plasmin, and the matrix metalloproteinases, including the membrane-type matrix metalloproteinases, play a major role. This article places emphasis on the biologic function and oncologic significance of cathepsins B and L, as well as on the urokinase plasminogen activator and the membrane-type matrix metalloproteinases localized on the cell surface. Recent investigations on these factors revealed that they are dependent on each other, such that the upregulation or downregulation also causes alterations in the regulation of the other factors. This fact alone elucidates the complexity of this system. Moreover, there is growing evidence that other proteases hitherto known to have other functions, e.g. as signal proteases in the immunologic system, may be important for invasion provesses. To provide an example of this, we describe the invasive potential of aminopeptidase N (APN/CD13). These recent results, which shed light on the role of further proteases in invasion processes, clearly show the complexity of this proteolytic system. Against this biologic background, it seems not to be promising to establish single proteases as distinct parameters for the prognosis of the metastatic potential of malignant tumors. PMID- 11217452 TI - [The role of inflammation in tumor invasion]. AB - While at first inflammatory reactions within the stroma of malignant tumors have been considered as a sign of immunological response to the tumor, there is now ample evidence that inflammation is able to promote tumor progression. It is now clear that tumor cells themselves direct the assembly of tumor stroma, using signalling pathways normally confined to inflammatory cells. By producing inflammatory mediators, tumor cells are able to recruit inflammatory cells to the tumor site, induce myofibroblasts and the production of extracellular matrix components. Paradoxically, the host reaction assists tumor progression by providing optimal conditions for growth and migration of tumor cells. In order to achieve a better understanding of malignant tumor progression, malignant tumors have to be regarded as a complex interactive microecosystem of tumor cells and stromal elements. PMID- 11217453 TI - [Pathology at Kiel University]. PMID- 11217454 TI - [Detection of isolated tumor cells in bone marrow: methodological aspects. A critical re-appraisal and prospects]. AB - Systemic dissemination of tumor cells occurring prior to the diagnosis or resection of the primary tumor is a prerequisite for relapse at distant sites and a major cause for death from cancer. Although detection of isolated tumor cells by sensitive immunocytochemical techniques is increasingly being considered as a clinically relevant prognostic factor, methodical objections including a questionable specificity of some of the antibodies applied, the heterogenity of the patient cohorts and the wide variation of the reported frequencies suggest that an independent prognostic impact of tumor cell detection in bone marrow at least for most of the tumor types still remains to be proven. When compared to non-morphological techniques immunocytochemistry is characterized by a lower false positive rate. So far a standarized application of this method still holds the most promise for clinical practice. Alternatively the genetic diagnosis of isolated tumor cells is hampered by a rather high false positive rate due to pseudogenes and illegitimate transcription. Appropriate negative controls in combination with a quantification of the PCR product are one possibility to overcome these difficulties. The clinical utility of genetic assays as a tool for the estimation of prognosis and management of cancer patients still remains an area of active investigation. PMID- 11217455 TI - Molecular pathology of lung cancer. AB - Our understanding of the molecular pathology of lung cancer is advancing rapidly with several specific genes and chromosomal regions being identified. Lung cancer appears to require many mutations in both dominant and recessive oncogenes before they become invasive. Several genetic and epigenetic changes are common to all lung cancer histologic types, while others appear to be tumor type specific. The identification of those specific genes undergoing such mutations and the sequence of cumulative changes that lead the neoplastic changes for each lung tumor histologic type remain to be fully elucidated. Recent findings in normal and preneoplastic bronchial epithelium from lung cancer patients and smoker subjects suggest that genetic changes may provide in this neoplasm new methods for early diagnosis, risk assessment and for monitoring response to chemoprevention. PMID- 11217456 TI - Analgesia and analgesic techniques. AB - In recent years, there has been a great increase in our understanding of pain mechanisms and our awareness of pain in small animals. Despite increased knowledge, many animals still go undertreated or untreated. Small exotic animals are a unique group of patients, and can prove challenging for the practitioner concerned with their welfare. This article reviews the process of nociception and how one can intervene in the pain pathway. Newer analgesic drugs are discussed, along with some novel administration techniques that can be adapted for small mammals. Ketamine has been regarded primarily as a chemical restraining agent, but new information reveals that it may have an important place in pain management. PMID- 11217457 TI - Crocodilian anesthesia. AB - With declining crocodilian populations worldwide, a greater interest in the conservation of these animals in the wild and in captivity is ongoing. This effort has created a demand for safe and effective ways to handle and immobilize crocodiles for transport and relocation. With the advent of new anesthetic protocols, working with crocodilians has now been made safer for both the animal and the handler. Unfortunately, current anesthetic protocols have been limited to a few species and further application of these protocols need to be undertaken with new species. PMID- 11217458 TI - Avian anesthesia. AB - Providing a safe anesthetic environment is the key to successful avian anesthesia. Knowledge and understanding the anatomic and physiologic differences between birds and mammals help to prevent most emergency situations and guide responses in critical situations. Thorough preanesthetic history and examination, correction of underlying conditions, and use of simple anesthetic protocols all optimize the outcome of the procedure. Finally, critical monitoring helps to anticipate most crises and reduces incidences of mortality and morbidity in avian anesthesia. PMID- 11217459 TI - Ferret, rabbit, and rodent anesthesia. AB - Ferrets, rabbits, and rodents are increasingly being presented to veterinarians for evaluation and treatment. The owners of these animals expect high-level medical and surgical care. Consequently, veterinarians are more often required to provide intensive anesthetic management of these animals. The variability of anesthetic agents used and patient responses are addressed. The consequences of size for anesthetic management are discussed. Successful small mammal anesthesia requires following general anesthetic principles, awareness of limitations, and maintenance of high standards of care. PMID- 11217460 TI - Fish, amphibian, and reptile analgesia. AB - Pain perception and appropriate behavioral responses are important for survival. The conservation of the opioid ligand and receptor suggests evolution of opioid receptors mediating antinociception throughout vertebrate phylogeny. Fish, amphibians, and reptiles have appropriate neurologic components, display the appropriate behavior in response to a painful stimulus, and possess antinociceptive mechanisms to modulate pain. Because pain perception in these species is therefore likely to be analogous to that of mammals, invasive and painful procedures should always be accompanied by appropriate analgesia and anesthesia. Although specific doses have not been established in clinical trials, clinicians should attempt to provide lower vertebrates with appropriate analgesia during painful procedures. Further experimental and clinical investigations are necessary to expand the current veterinary literature in the area of pain and analgesia in lower vertebrates such as fish, amphibians, and reptiles. PMID- 11217461 TI - Physical restraint techniques and immobilization equipment. AB - The art of safe and effective restraint of non-domestic patients can aid in their management and facilitate their health care delivery. This article discusses some of the strategies and basic equipment required in handling these unique patients more commonly seen by veterinary practitioners. These restraint procedures may offer an alternative to anesthesia for minor, less stressful procedures that do not involve pain. PMID- 11217462 TI - Marsupial, insectivore, and chiropteran anesthesia. AB - This article covers the manual restraint and anesthesia of marsupials, insectivores, and chiroptera. Marsupials commonly kept as pets in the U.S. [e.g., eastern gray kangaroos (Macropus giganteus), Bennett's wallabies (Macropus rufogriseus), and sugar gliders (Petaurus breviceps)] are covered in detail. Marsupial species kept in zoological parks [e.g., Tasmanian devils, koalas (Phascolarctos cinereus), and common wombats (Vombatus ursinus)] are covered in less detail. Of the insectivores, only the African hedgehog (Atelerix albiventris) and the European hedgehog (Erinaceus europaeus) are commonly kept as pets and, consequently, the insectivore section concentrates on discussing these two species. The section on chiropteran anesthesia is divided into two broad categories: the megachiropterans (flying foxes and fruit bats) and the microchiropterans (insectivorous bats). Most of the information on the species covered in this article is anecdotal, and this should be kept in mind when using the anesthesia protocols described. PMID- 11217463 TI - Primate anesthesia. AB - This article provides an update on some of the recent advances in primate anesthesia. It focuses in particular on some of the newest information available regarding the effects of opioids and alpha-2 agonists in primates, and how these effects are different from what we might expect in other companion animals. It reviews the important properties of the latest induction and inhalation agents, and stresses the need for continuous monitoring of the anesthetized patient. PMID- 11217464 TI - Chemical immobilization of felids, ursids, and small ungulates. AB - Private ownership of wild animals is on the rise. With the advent of potent new sedative agents, many practitioners now receiving these cases have the means to increase the safety and effectiveness of chemical immobilization in many wildlife species. Chemical immobilization is actually the induction of anesthesia. In many cases, induction alone suffices to achieve some management or medical goal, whereas in other cases, maintenance anesthesia is required. One quickly realizes that once these species are induced, maintenance anesthesia is often familiar, based on experiences with domestic animals that bear close similarity to the species discussed in this chapter. Induction and recovery of wild animals requires special attention to details to prevent "fight or flight" responses from marring the success of a sedation procedure. Although potent novel drugs allow veterinarians to expand their practice horizons, it is vital to evaluate legal and safety issues thoroughly before engaging in the care of wildlife species on a regular basis. PMID- 11217465 TI - Avian analgesia. AB - Understanding behavioral indicators of pain and other assessment techniques can help one to recognize pain in birds and prompt us to treat birds with analgesics. An analgesic plan needs to include several modalities to help reduce pain in the avian patient. Analgesic therapy should be directed at treating the disease/injury in the periphery, and the changes that occur in the central nervous system (CNS). Both opioid and nonsteroidal anti-inflammatory drug (NSAID) therapeutics can be selected to provide analgesia for the avian patient. PMID- 11217466 TI - Analgesia of small mammals. AB - Small mammals receive analgesics much less frequently than more familiar species such as dogs and cats. This is probably related to the greater difficulty of recognizing pain in these species, and the uncertainty as to the most appropriate analgesic regimen to implement when the presence of pain is suspected. However, the same principles of pain assessment and analgesic use that are applied when dealing with other companion animals can be used to manage pain effectively in small mammals. All of the commonly used analgesic agents can be used safely and effectively in small mammals, although the size of many of these animals limits the use of techniques such as epidural administration or transdermal drug delivery systems. As with other species, it is important to integrate an analgesic regimen with the overall scheme of perioperative care, and to try to implement preemptive and multi-modal analgesic therapy. PMID- 11217467 TI - Invertebrate anesthesia. AB - One hundred years ago (January 5th, 1901), an article in the Veterinary Record declared: The use of chloroform by practitioners is now common, and the amount of pain and suffering prevented is enormous. By its aid we are enabled to perform operations with success which without it were seldom satisfactory. A century later, in an age of sophisticated veterinary medicine, those words seem quaint, a relic of a bygone age. Our understanding of anesthesia of invertebrates in 2000 is very much at a comparable stage, however, and a great deal of research is needed to remedy this situation. PMID- 11217468 TI - Fish and amphibian anesthesia. AB - This article is designed to provide the veterinary practitioner with some basic information on how to anesthetize fish and amphibians. General guidelines regarding working with these aquatic animals are covered. Specific topics include methods of anesthetic delivery, anesthetic monitoring, and recovery. Various anesthetic regimes and dosages are presented both in the text and in table form. PMID- 11217469 TI - Reptile anesthesia. AB - Successful reptile anesthesia requires patience, planning, and understanding of normal anatomy and physiology in health and disease. Reptiles make good anesthetic patients because of their physiologic resilience. New drugs that are not only safe and efficacious, but also result in relatively short recovery times, have greatly enhanced the design of anesthetic regimens. Further studies are required to quantitatively evaluate the physiologic effects of drugs used and validate available monitoring modalities for use in a wide variety of reptiles. PMID- 11217470 TI - Video-assisted thoracic surgery--state of the art. AB - Video-assisted thoracic surgery (VATS) is one of the main medical revolutions of the past decade. For its satisfactory performance, the following prerequisites are essential: (1) knowledge and experience in thoracic surgery; (2) team of experienced anesthesiologists; (3) preoperative assessment of respiratory function; (4) adequate postoperative care; and (5) instruments specially designed for thoracoscopic surgery. VATS is routinely performed under general anesthesia with double lumen endotracheal intubation for separate control of each lung. Insufflation of carbon dioxide must not exceed 1-3 mm Hg. Too high pressure may cause harmful reduction of venous return and mediastinal shift with impairment of ventilation. Presence of adhesions should be determined by finger exploration of the pleural cavity. Operative ports should be placed carefully, avoiding damage to the intercostal nerves and vessels. The video technique can be used with efficiency for the following indications: pneumothorax, resection of pulmonary nodules, biopsies of lung, pleura and mediastinal structures, resection of mediastinal tumors, management of empyema, and hemostasis and closure of lacerations after trauma. Indications for esophageal procedures include esophagomyotomy for achalasia and resections of benign lesions. Repair of perforated esophagus is a matter of controversy, but in early stages it can be done thoracoscopically. Although video-pericardioscopy has been performed by some surgeons, this procedure can be done easier and faster using the direct approach without the video equipment. There are differences of opinion with regard to major pulmonary and esophageal resections for cancer. The apparent advantage of diminished pain is offset by inadequate resection, spread of malignant cells and potential damage to the resected specimen with loss of important information concerning pathology. Complications of VATS are few, and include prolonged air leak, dysrhythmia, respiratory failure, bleeding and infection. Due to progress over the past several years, VATS has become an inseparable part of thoracic surgery and should be included in the basic training of every thoracic surgeon. PMID- 11217471 TI - [Short- and long-term monitoring with high-resolution ultrasonography of postoperative thyroid residue. Personal experience with 200 thyroidectomies]. AB - BACKGROUND: After having abandoned conservative operations of the thyroid (partial resection, enucleal resection) today total thyroidectomy and sub-total thyroidectomy and near total thyroidectomy are the operations of choice. Cause the frequent post-operative scintigraphic signs, on the 3rd month, of thyroidal residue of significative size, founded in our patients operated for sub-total thyroidectomy, we begun to study the echografical monitoring of the thyroidal recess. METHODS: From January 1995 to December 1997 we operated 200 patients for Thyroidectomy. The kinds of operations were: total thyroidectomy for 96 patients (48%), sub-total thyroidectomy for 64 patients (32%), and near total thyroidectomy for 40 patients (20%). We controlled all the patients by ecografical monitoring of the thyroidal recess to detect and to determinate the possible thyroidal residue, that it will be monitorized on the 7th day, on the 1st month, on the 6th month and on the 12th month. We measured the thyroidal residual dimensions and volume. We recorded all the examinations by VCR or film and after we elaborated the results by exponential graphics. The patients that showed the thyroidal residues underwent to a scintigraphy. RESULTS: The thyroidal residuals were measured within the 7Th post-operative day. In the following controls we have noted a thyroidal residue hypertrophy. Multinodular goither was the disease with the highest degree of growth (until the 200% of the first measure of the residue). After an initial phase of growth almost all the patients showed a trend to the stabilization, with the exception only of the patient that suffered from multinodular goither. The scintigraphic examination was not realiable, in our experience, about the mathematic measurement of the thyroidal tissue, showing always an overvaluation of the residue. The best specificity was showed by US-HR. CONCLUSIONS: The patient that undergoes to total thyroidectomy needs an adequate suppressive and substitutive therapy. We identify the presence of several stimulating factors the growth of the residual thyroidal tissue that could arise to promote the hyperplasia and the hypertrophy of the parenchyma (EGF, TSG, TSI, PG). There are factors that are unidentified and are not subject to the suppression caused by substitutive therapy. PMID- 11217472 TI - [Difficulties in defining and diagnosing gastroesophageal reflux: practical implications in surgery]. AB - Today, it is difficult to set a correct definition and diagnosis of gastroesophageal reflux disease. The attempt to define it on the basis of "typical" symptoms, like heartburn and regurgitation, or "atypical" symptoms, like chronic cough, asthma, hoarseness and thoracic pain, or on the basis of endoscopic esophagitis presents notable difficulties. Moreover, the problem of a correct definition is tightly tied up to the ability to set a correct and early diagnosis. There are many diagnostics tools, but none of them is the golden standard. Today, the trend is to emphasize the role of the 24-hour pH-monitoring in diagnosing the reflux in those symptomatic patients with no visible esophagitis. However, its limit is to underline only the acid, not the duodenogastric alkaline reflux, which is also very important in the genesis of the inflammatory esophageal lesions. The esophageal manometry, however, evaluates only the mechanical state of the lower esophageal sphincter and the peristaltic function of the esophageal body but does not provide any direct information about the exposure of the esophagus to the gastric juice. The aim of this study is to analyze the problems concerning the definition and the diagnosis of the gastroesophageal reflux disease with particular attention to the practical implications on the common surgical practice, and to review some solutions reported in the literature for the difficult clinical approach to the patient with this pathology. PMID- 11217473 TI - [Cell-mediated immunity after laparoscopic cholecystectomy]. AB - Cell-mediated immunity (CMI) is temporarily decreased after major surgical procedures in relation to type of anaesthesia, length and severity of an intervention. In this study it has been evaluated CMI response in vivo, after laparoscopic (LC) and open cholecystectomy (OC). 5 healthy persons and 16 patients with symptomatic and uncomplicated gallstones were studied. They were subdivided in two groups: 8 were treated by OC, 8 by LC. A skin test system (Multitest, IMC-Institute Merieux, Lyon, France) consisting of a plastic disposable multiple-puncture device capable of simultaneous application of seven delayed-type hypersensitivity antigens and a glycerin and saline diluent (negative control) was used. The test was performed 48 hours before and 24 hours after the surgical procedure. A diameter of 2 mm or more of the induration was considered as a positive response. A score expressed, as the sum in millimeters of all the mean diameters (DM) of positive reactions and as numbers of antigens (NA) positive was calculated. Statistics was assessed by Student's t test for comparison of averages. There was no difference of age, sex, anesthesiologic risk, length of the operation between the two groups. We observed a significative reduction of DM (P < 0.05) and of NA (P < 0.05) in patients in which OC was performed while there were no significant in the group treated by LC. Results show a significant suppression of the CMI after OC, no particular changes after LC according to other studies in vitro. PMID- 11217474 TI - [Complicated Spigelian hernia: our experience]. AB - We present a case of complicated Spigelian hernia presented with symptoms of intestinal occlusion, in a 50 years old woman. Spigelian hernia represents 1-2% of all abdominal hernias and can occur anywhere along the semicircular line of Douglas. The patient underwent emergency surgery followed by polypropylene plastic repair. The postoperative course was uneventful and the patient was discharged on day 8 post intervention in good general conditions. The 2 years follow-up showed no recurrence of the disease. Clinical examination is the foundation of the diagnosis, whereas radiological findings (ultrasonography, TC) allow the exclusion of other pathologies in the differential diagnosis. The preoperative diagnosis is difficult, mainly because of the non-specificity of symptoms as well as the few cases reported in the literature. In conclusion, we remark that the surgery remains the most effective treatment of Spigelian Hernia. PMID- 11217475 TI - [Current trends in the treatment of rectal carcinoma]. AB - Authors report their personal experience about 336 cases of curative surgery for rectal cancer. They describe technical surgical details universally accepted in Literature such as sharp total mesorectal excision, the extension of lymphadenectomy with high ligature of inferior mesenteritis artery while pelvic lymphadenectomy seems to be unuseful and burdened by high morbidity; finally they underline advantages offered by a colic pouch above all for lower incidence of anastomotic leakages. As adjuvant therapy is concerned, our actual tendency is a preoperative radiochemiotherapy of which we are still evaluating long-term results. Finally we analyzed correlations between cellular genetics and colo rectal cancer. PMID- 11217476 TI - [Results of laparoscopic bilateral varicocelectomy]. AB - Left varicocele (LV) is a common clinical condition that is present in approximately 15% of the general male population. Bilateral varicocele (BV) is an association of clinical LV and subclinical or ultrasound diagnosed right varicocele. Recent diagnostic technology suggests that BV is much more common than previously suspected varying from 15 to 57%. The laparoscopic technique offers the possibility of planning bilateral varix ligation but only a few reports are currently available. The aim of this study was to evaluate the outcome of contemporary bilateral correction of BV on spermatogenesis. From 1992 January to 1998 December a total of 207 patients with clinical left varicocele and a pathological sperm count were studied. Scrotal sonography was performed and in 96 patients (group A) subclinical right varicocele was diagnosed while 111 patients (group B) only had LV. 84 patients were married and had tried unsuccesfully for a pregnancy for at least one year before evaluation. All patients underwent laparoscopic varicocelectomy, performed under general anesthesia with a three trocar technique with application of clips to the spermatic vein and resection. Patients with right reflux received bilateral varix ligation. Operating time averaged 28 minutes for unilateral cases and 42 minutes for bilateral legatures. No significant differences were found in age distribution or preoperative seminal paramenters between the two groups. Postoperative hospital stay was 1.2 and 1.3 days respectively. 168 patients underwent sperm count four to six months after surgery. Both groups showed improvements in number (group A 41 millions, group b 27 millions), 2nd hour motility (group A 32%, group B 19%) and morphology (group A 52%, group B 51%). 95 patients achieved normalization of seminal parameters, 40 (63%) in group A and 37 (30%) in group B, and there was a statistically significant difference between the two groups. The pregnancy rate was calculated on married population after one year; it was 41% in total. The role of the subclinical right varicocele associated to clinical left varicocele is uncertain and there are few papers concerning this argument. In this serie normalization of seminal parameters and the pregnancy rate were significantly higher in patients with bilateral correction of reflux. In conclusion our data confirm that subclinical right reflux also has a detrimental effect on spermatogenesis and we suggest that it must be corrected contemporary when associated with clinical left varicocele. PMID- 11217477 TI - [Post-traumatic diaphragmatic hernia with late diagnosis. Report of a clinical case]. AB - Starting from the observation of a case of late diagnosed left-side hernia after traumatic rupture of diaphragma, the authors consider the increasing incidence of this pathology during the years. The increased frequency of thoraco-abdominal traumas and the more sophisticated diagnostic tools, permit an earlier diagnosis nowadays. In our patient the diagnosis was made late on the basis of the standard x-ray of the thorax. The CT scan of the thorax and of the abdomen gave more informations. Left thoracotomy enabled a wide exposure of the herniated viscera; the breakthrough of the diaphragm was repaired by means of interrupted suture and it was necessary to apply two prostheses of synthetic material. PMID- 11217478 TI - [Lymphangiomatosis of the spleen. Report of a clinical case]. AB - Lymphangiomatosis confined to the spleen is a very are condition. The authors in this article describes one new case and briefly reviews the literature. In this case, after the exclusion of an hydatidosis of the spleen, a total splenectomy was performed. The histologic findings confirmed the lymphangiomatosis of the spleen. The authors emphasize the surgical strategy in splenic lymphangiomyomatosis, infact the total splenectomy is mandatory, because the splenic parenchyma is nearly completely substitute by the cysts. For this reason is preferably, before surgery, to perform the antibateric profilaxis against the OPSI. PMID- 11217479 TI - Malignant lymphoma complicating ulcerative colitis. AB - Carcinoma of the colon as a complication of chronic ulcerative colitis is relatively common, whereas malignant lymphoma is apparently rare. We report two cases of patients with malignant lymphoma complicating ulcerative colitis, a CD 30 + T-cell lymphoma of the intestine and a low grade B-cell non-Hodgkin's lymphoma of MALT type. It is important to be aware of the possibility of malignant lymphoma in ulcerative colitis in order to evaluate correctly any lymphoid infiltrate seen in a biopsy, especially when anti-inflammatory treatment seems to be ineffective or when symptoms change. PMID- 11217480 TI - [Angiodysplasia of the large intestine: unusual rectal localization]. AB - The authors report a case of lower gastrointestinal hemorrhage in a 69-year-old male, in which the sequence colonoscopy-angiography identified the source of bleeding as a rare Angiodysplasia (AD) of the rectum. Such vascular abnormalities are one of the most common causes of major lower gastrointestinal tract bleeding in the elderly and usually occurs predominantly in the right side of the colon. The clinical presentation of Angiodysplasia is varied and accurate diagnosis usually requires a combination of diagnostic techniques such as colonoscopy and angiography. The optimal management is uncertain and should be individualized for each patient depending on severity and rate of rebleeding. A conservative medical approach is indicated for many patients, while endoscopic treatment does not seem modify the risk of recurrent bleeding. In case of massive hemorrhage or recurrent bleeding surgery still represents the definitive treatment for Angiodysplasia. However the risk of rebleeding following surgery is a considerable problem and varies in literature from 5% to 30%. PMID- 11217481 TI - [Inguinal hernioplasty with calibrated prosthesis (personal modification of the Trabucco technique]. AB - From January 1994 to December 1997, the authors operated on 636 patients with primary inguinal hernia, using an original modification of Trabucco's tension free and sutureless technique. The hernial defect is sized according to Gilbert's classification modified by Rutkow and Robbins and repaired with one or more plugs (up to four in the authors' experience) in relation to its extent. The posterior wall is reconstructed over the plugs encompassing the transversalis fascia and a wing of the plug superiorly and the iliopubic tract inferiorly. The double-layer polypropylene mesh is fashioned intraoperatively and the key-hole tailored to the variable distance between the spermatic cord and the pubic tubercle. All patients ambulated immediately after the operation, had a light meal two hours later and were discharged within one day of surgery. During a 3 months to 4 year follow-up only one recurrence has been recorded (0.16%). The proposed technique allows to perform a repair to measure ("calibrated") with minimal pain, immediate rehabilitation and early return to unrestricted activity. PMID- 11217482 TI - [Clinical manifestations of herpetic keratitis and uveitis]. AB - Herpetic keratitis and uveitis probably represent two of the most under- and misdiagnosed diseases affecting the anterior eye segment despite their being major causes of blindness in developed countries. Recurrences are pathognomonic of herpetic eye disease and are responsible for the high socioeconomic costs of this affection. In recent years, the application of molecular biological methods and the results of long-term clinical studies have afforded us new insights into the pathophysiology of herpetic eye disease and have advanced our perception of how best to manage it. This article summarizes our current understanding of the pathophysiology of herpetic eye disease and, in the light of this wisdom, discusses specific conditions (epithelial and geographic keratitis, ulcerating and non-ulcerative stromal keratitis, disciform keratitis/endotheleitis, uveitis and metaherpetic keratitis) as well as contemporary therapeutic and prophylactic strategies. The possible mechanistic basis of recurrence is also dealt with, as is the sociomedical relevance of the disease. In addition to providing a documentation of typical clinical pictures, the article also furnishes information respecting the course of the disease, its diagnosis and treatment. PMID- 11217483 TI - [The role of HIV associated eye changes in the time of HAART (highly active antiretroviral therapy]. AB - Choice of an appropriate treatment strategy in the handling of HIV infection has become problematical, owing to the very serious side effects that sometimes develop in conjunction with antiretroviral combination therapy (HAART). Indeed, the severity of these affections can assume such a magnitude as to render an abatement or even the interruption of treatment imperative in a not inconsiderable proportion of patients. In such individuals, HIV-associated opportunistic diseases thus constitute a major concern. As regards the ocular system, three diseases are regularly encountered: HIV-associated retinal microangiopathy, cytomegalovirus (CMV)-retinitis and immune-recovery uveitis, the latter being a recently recognized condition which is manifested after immune reconstitution in patients with a history of viral retinitis. Retinal microangiopathy assumes significance in that it signals uncontrolled replication of the retrovirus. Viral retinitis hallmarks an actual breakdown of the functional immune response and may be observed in patients undergoing HAART even if their CD4 counts are above 100 per microliter. The treatment of this condition is crucial for the prolongation of survival and in so far as its manifestation renders an estimation of when systematic recurrence prophylaxis should be interrupted extremely difficult. Furthermore, reactivated retinitis is sometimes difficult to distinguish from immune-recovery uveitis--an immune restoration reaction which is probably directed against persisting CMV antigens. This circumstance may account for the impaired visual function attributable to chronic macular edema and epiretinal membrane formation. PMID- 11217484 TI - [Age-related macular degeneration (AMD)--therapeutic possibilities and new approaches]. AB - Age related macular degeneration (ARMD) is one of the leading causes of irreversible vision loss in patients over 65 years of age. Nearly 30 percent of persons over 75 years of age will suffer from ARMD. The etiology is not yet fully understood. Besides age, many risk factors such as gender, arterial hypertension, arteriolosclerosis, elevated serum lipids, smoking, alcohol abusus, and exposure to UV light are being discussed. Genetic factors are certainly involved as well; familiar predisposition is assumed in more than 50 percent of cases. White individuals are more affected than colored ones. Predisposing ocular signs are macular drusen, focal hyperpigmentation, and light eyes. In this review, anatomical, pathophysiological and fluorescein-angiographic features and the clinical classification of exudative and dry stages of ARMD are described. Concepts of management of ARMD include pharmacological measures, laser treatment, photodynamic therapy, and surgery including excision of submacular choroidal neovascular membranes and macular translocation. Success rates of any therapeutic method are very limited. Low vision aids are promising by improving quality of life in many cases. PMID- 11217485 TI - [Central retinal artery occlusion--etiology, clinical picture, therapeutic possibilities]. AB - An occlusion of the central retinal artery (CRAO) leads to a unilateral acute painless loss of vision. The individual etiology remains unclear in many cases. Potential pathomechanisms are embolism, vasoobliteration and vascular compression. Emboli (calcified, thrombotic, myxomatous, bacterial or cholesterol) are of carotid or cardiac origin. Atherosclerotic plaques, giant-cell arteritis and other types of vasculitis may cause vasoobliteration. A retrobulbar mass (hematoma, neoplasms, retrobulbar injections) may lead to an optic nerve and central retinal artery compression. Funduscopic signs of CRAO are described. Late development of iris neovascularization and neovascular secondary glaucoma may occur in up to 15 percent of cases. The prognosis of CRAO has been poor. A spontaneous remission and recovery of visual function is rare. It has been shown experimentally that the retinal damage is irreversible after 100 minutes of non perfusion. The initial treatment should include an immediate paracentesis of the anterior chamber, digital massage of the globe, and i.v. administration of 500 mg azetazolamide in order to stimulate retinal reperfusion by lowering the intraocular pressure. This procedure is recommended for the first 6 (up to 24) hours after onset of CRAO. More promising success rates have recently be reported by a selective intra-arterial fibrinolysis with Urokinase (100,000-1,000,000 IU) or recombinant plasminogen activator (rtPA). In a personal series of 18 cases, intra-arterial fibrinolysis with Urokinase was performed. A final visual acuity of 6/10 to 6/6 was achieved in 30 percent of the cases. PMID- 11217486 TI - [Diabetic retinopathy--pathophysiological knowledge and modern treatment methods]. AB - Diabetic retinopathy (DR) leads to visual impairment in the majority of patients suffering from diabetes mellitus for more than 20 years. Endothelial damage, capillary dropout, and vasoproliferative activity of various growth factors are some of the complex pathophysiologic events that lead to retinal damage. Insufficient blood glucose control and arterial hypertension are the leading risk factors for the progression of DR. Adequate therapeutic measures depend on timely and regular ophthalmologic examination. Laser photocoagulation prevents severe visual loss in about 50% of cases with proliferative DR and high risk factors as defined by the Diabetic Retinopathy Study Group. Dosage of laser treatment depends on the stage and severity of DR and requires appropriate experience of the surgeon. Introduction of modern vitreoretinal surgery has yielded considerable progress in the management of vitreous hemorrhages (VH) and tractional retinal detachment in advanced stages of proliferative DR. Results of vitrectomy in 765 cases with proliferative DR are presented. Visual loss can be prevented in over 70% of cases with simple VH without retinal detachment and limited neovascularization, but in only about 30% of cases of VH complicated with retinal traction detachment and extensive vasoproliferation. PMID- 11217487 TI - [Eye diseases in mitochondrial encephalomyopathies]. AB - Mitochondria are the principal site of generation of energy in form of adenosine triphosphate (ATP). They contain the enzymes of the Krebs and fatty acid cycles and the respiratory pathway. Ocular tissues with high energy consumption and dependence on oxidative energy production like the optic nerve, the retina, and the pigment epithelium are often involved in mitochondrial diseases. This article reviews the genetic mitochondrial diseases involving the visual system. Their most important ocular findings include: acute or slowly progressive bilateral visual loss and visual field loss due to an optic neuropathy or retinal degeneration, bilateral progressive decreased ocular motility, and bilateral upper lid ptosis. The following diseases are discussed: Leber's Hereditary Optic Neuropathy (LHON); Kearns-Sayre Syndrom (KSS); Chronic Progressive External Ophthalmoplegia (CPEO); Autosomal Recessive Cardiomyopathy, Ophthalmoplegia (ARCO); Mitochondrial Encephalomyopathy, Lactic Acidosis, Stroke-Like Episodes (MELAS); Neuropathy, Ataxia, Retinitis Pigmentosa (NARP); Mitochondrial Neuropathy, Gastro-Intestinal Encephalomyopathy (MNGIE); Myoclonus Epilepsy, Ragged-Red-Fibers (MERRF); Wilson's disease; Friedreich's ataxia. Diagnosis of mitochondrial encephalomyopathies is established by screening for mutations in blood or muscle biopsy samples. No specific therapies which influence the course of mitochondrial encephalomyopathies are known. Drugs interacting with the mitochondria function, alcohol consumption and smoking should be avoided. PMID- 11217488 TI - [Surgical correction of refractive errors]. AB - This article reviews operation techniques and indications for the surgical correction of ametropia. The author also explains and lists the anomalies of refraction. The limitations of the methods as well as open questions for the future are discussed. PMID- 11217489 TI - [Eye diseases in sleep apnea syndrome]. AB - Sleep apnea syndrome is characterized by recurrent complete or partial upper airway obstructions during sleep and recognized as an important risk factor for cardiovascular and cerebrovascular diseases. Several eye diseases have been associated with sleep apnea syndrome. Due to floppy eyelids often a chronic conjunctivitis occurs. A leaking mask used for apnea treatment may also induce a conjunctivitis. The lids may show an upper lid ptosis, lower lid ectropium, blepharochalasis, or trichiasis. Corneal findings include infectious keratitis, dry eye, recurrent erosion, keratoconus, and progressive endotheliopathy. Several optic neuropathies also seem to be associated with sleep apnea syndrome. PMID- 11217490 TI - [Pharmacological therapy approaches in ocular traumatology]. AB - Ocular trauma is the most common reason for unilateral blindness. In the last 15 years tremendous advances in diagnostics (CT, MRI, ultrasound) and surgery (pars plana vitrectomy, phacoemulsification, intraocular lenses) have been made. Furthermore new medical therapies to sustain treatment of eye accidents have been developed. On the basis of various traumatic diseases (abrasio, chemical injuries, hyphema, cataract, photothermal retina lesion and optic neuropathy) appropriate of these medical therapies are to be discussed. PMID- 11217491 TI - Gender bias in families and its clinical implications for women. AB - Within the framework of feminist theory, this clinical study of 45 women with brothers explores family-based gender bias and elucidates its role in the lives of women. Bias is conceptualized along three dimensions: (1) devaluation--the woman perceives that she was less valued by her parents than a brother; (2) abuse without redress--the woman reports that she was abused by a brother and perceived herself as unable to get redress from her parents; and (3) deprivation--the woman perceives herself to have been deprived of resources or privileges that a brother had. The author identifies several legacies from the girlhood experience of gender bias that may be associated with depression in women: involvement in demeaning intimate relationships; self-doubt about competence in comparison with males; an isolating distrust of relationships; and the sacrifice of personal and relational development to serve parents and compensate for problematic brothers. Components of treatment are the therapist's self-awareness of internalized sexism; the questioning of client beliefs, based on sexist assumptions, that devalue women; and expanding women's perceived range of choice for improving their lives. PMID- 11217492 TI - Cultural and linguistic considerations in psychodiagnosis with Hispanics: the need for an empirically informed process model. AB - It is estimated that in the next century nearly half of the clientele seeking mental health services will be members of ethnic minority groups. Hispanics are the most rapidly growing population in the United States, and epidemiological evidence suggests that they present higher levels of psychiatric symptomatology and prevalence rates of disorder compared with other ethnic groups. Despite the unprecedented recognition of cultural considerations found in DSM-IV for rendering a psychiatric diagnosis, there is still surprisingly little empirical research examining cultural and linguistic factors influencing the diagnostic process. This article critically reviews this research and considers process variables that can inform social workers' culturally sensitive diagnosis of Hispanics. PMID- 11217493 TI - Reading social work. PMID- 11217494 TI - Beyond therapy: bringing social work back to human services reform. AB - Based on field interviews in a Chicago community development corporation and settlement houses in New York City and St. Louis, as well as interviews with leading social services innovators and social work educators, this article explores the intersection of current social work practice and human services innovation. The article offers a rationale and a blueprint for a reorientation of social work's "helping relationship," reviews a number of promising innovations and strategies that may help the profession make this reorientation operational, and explores forces restraining as well as driving such change. PMID- 11217495 TI - Complexities of coalition building: leaders' successes, strategies, struggles, and solutions. AB - Government and private funding initiatives are promoting coalitions, collaborations, and other interorganizational approaches to address complex community, social services, and health issues. Social work organizers and administrators are increasingly leading coalitions themselves or representing their organizations in collaborative planning and problem solving, often without understanding how to manage the complexities involved in interorganizational relationships. This article reports on aspects of a larger quantitative and qualitative research project that studied coalition dynamics, operations, and outcomes. Coalition leaders interviewed defined success in multiple ways. Competent leadership was the factor most often identified with coalition success. PMID- 11217496 TI - Targeting women donors: a response to "Women and human services giving". PMID- 11217497 TI - Response to Sun. PMID- 11217498 TI - Nature of work and future of the social work profession. AB - Social work practice and education long have been influenced by trends in the U.S. economy, particularly as these trends affected patterns of employment and unemployment. This article assesses the implications of recent changes in patterns of economic production and the nature of work for the social work profession. The authors conclude with recommendations on how schools of social work can address these implications in their curricula and their relationships with the communities in which they are located. PMID- 11217499 TI - Work first: reflections on the welfare-to-work movement in America. PMID- 11217500 TI - [After 1440]. PMID- 11217501 TI - [Radon and domestic exposure]. AB - Radon is a noble gas derived from the decay of radium, which itself is a decay product of uranium. The decay products of radon can collect electrostatically on dust particles in the air and, if these particles are inhaled and attach to bronchial epithelium, produce a high local radiation dose. Alpha particles can induce DNA double-strand breaks and the development of cancer. A causal relation between lung cancer and radon exposure and its progeny has been demonstrated in epidemiological studies of miners. Radon exposure became a public health issue almost 15 years ago. Most radon exposure occurs indoors, predominantly in the home. There is however, a wide range of radon concentration values in different countries. The highest level occurs in areas with granite and permeable soils. The risk for smoking, the leading cause of lung cancer, is far greater than for radon, the second leading cause. The estimates obtained from case-control studies of indoor radon are very contradictory. Scientific knowledge of effects of low levels of exposure to radon and the role of cigarette smoking, as a combined factor, must be studied. Smoking and radon probably interact in a multiplicative fashion. PMID- 11217502 TI - [Strategy for early diagnosis of lung involvement in systemic scleroderma]. AB - Systemic sclerosis (SSc) is an autoimmune disorder characterized by accumulation of collagen in affected organs, mainly the skin and the lungs, associated with abnormalities of the arterioles and capillaries. There are two types of pulmonary involvement, which influence long term prognosis: infiltration of the lungs and/or pulmonary artery hypertension. Full investigations into possible lung involvement must be performed systematically when SSc is diagnosed and during follow-up. The double pathophysiology sometimes makes diagnosis difficult but it must be made as early as possible in order to decide on the optimal treatment. The aim of this study was to evaluate the usual explorations and to propose biological markers to identify patients requiring more detailed lung investigations, in order to establish a diagnostic approach to treatment and follow-up patients with SSc. PMID- 11217503 TI - [Postoperative complications after radiochemotherapy or chemotherapy for bronchial cancers]. AB - OBJECTIVE: The purpose of this study was to evaluate the risk of lung cancer surgery, following induction chemo and/or radiotherapy. METHODS: This retrospective study included 69 patients treated from January 1990 to January 1998 for a primary lung cancer in whom surgery had been performed after induction treatment. Surgery had not been considered initially for the following reasons: N2 disease (IIIA; n = 25), temporary functional impairment (2 stages IB and 2 stages IIIA [N2]; n = 4); doubtful resectability (stage IIIB [T4]; n = 40). The medical regimen resulted in combined radio-chemotherapy in 43 patients who received 2 to 4 cycles of chemotherapy (average = 2.9 +/- 0.8 cycles) and 43 +/- 8 Gy (20 to 60 Gy), or chemotherapy alone in 26 patients (3 +/- 0.7 cycles). RESULTS: Exploratory thoracotomy was performed in 4 patients (6%). The in hospital mortality was 9% (n = 6) from respiratory origin in all cases. There were 4 reoperations (6%): 3 for bronchial fistula and 1 for bleeding. Thirty five patients (51%) required blood transfusion (4.5 +/- 3.8 cell packs). The incidence of early and delayed bronchial fistula after pneumonectomy was 15%. Thirteen patients had a postoperative pneumonia (19%). CONCLUSION: Surgery for lung cancer after induction chemo and/or radiotherapy is associated with an increased risk. While the mortality seems "acceptable", the morbidity rate however is high. PMID- 11217504 TI - [Prognosis of asthmatic adolescents in adulthood]. AB - Little is known about the long-term outcome of asthmatic adolescents. According to the literature, 20 to 50% of asthmatic adolescents become symptom-free when they become adults. We report 50 cases of asthmatic adolescents, 25 girls and 25 boys, with a mean follow of 4.4 years (range 1-12 years). Only 4 patients (8%) became symptom-free, all 4 were stage I and II patients. One death occurred subsequent to penicillin allergy, but was not related to status asthmaticus. Nor remission was observed in stage III and IV patients, whereas 5.8% and 12% of stage II and II patients respectively grew out of their asthma. The factors predictive of persistent asthma in adulthood were severe asthma at the age of 13 years, female gender, onset of asthma before the age of 7 years, no periodic rhinitis, and exercise induced asthma. PMID- 11217505 TI - [Malignant mediastinal lymph node tumors with unknown primary cancers]. AB - PURPOSE: Malignant mediastinal lymph nodes with unknown primary tumor is a rare occurrence. The purpose of this study is to specify some characteristics of the patients presenting with this disease and to define an adequate therapeutic approach. MATERIAL AND METHODS: Between 1985 and 1997, we have operated on 54 patients with isolated non-small cell malignancy to mediastinal lymph nodes. Forty-nine patients underwent surgical biopsy of the mediastinal mass, generally followed by radiation therapy and/or chemotherapy. A mediastinal lymph node resection was performed in 5 patients. RESULTS: Five patients were lost to follow up (9.3%). The 5-year survival rate and the median survival were 12.4 +/- 5% and 7 months respectively. Four of the 7 patients who were still alive after follow ups ranging from 10 to 68 months had undergone a lymph node resection. During the follow-up, a primary tumor was discovered in only 5 patients (11.4%). CONCLUSIONS: Patients with isolated malignant lymph nodes of the mediastinum have a poor prognosis. In order to improve their survival, we recommend a more aggressive therapeutic approach comprising a chemotherapy and a mediastinal lymph node resection, associated in some cases with a lung resection. Radiation therapy of the mediastinum can be administered, principally in case of incomplete resection. PMID- 11217506 TI - [Dry cough in a 17 year old patient]. AB - We present a case of mediastinal ganglioneuroma observed in a 17-year-old girl. Imaging suggested the diagnosis that was confirmed histologically on a peroperative specimen. Mediastinal ganglioneuroma is a highly uncommon tumor with characteristic imaging features that is quite difficult to resect. PMID- 11217507 TI - [Post-cardiac injury syndrome: an rare cause of pleurisy, value of pleural fluid analysis]. AB - The post-cardiac injury syndrome is an inflammatory process concerning the pericardium, the pleura and/or the pulmonary parenchyma, that develops after different kinds of cardiac aggression. The diagnosis can be evoked when some clinical and biological results are present but remains one of exclusion. We report a case of post-cardiac injury syndrome for which we demonstrate an immunologic involvement of the pleura. The antimyocardial antibodies and the low complement index found in the pleura strongly support an immunologic process, and this suggests that the analysis of the pleural fluid could be useful for the diagnosis of the post-cardiac injury syndrome. PMID- 11217508 TI - [Lemierre syndrome: clinical and radiological characteristics of a rare disease]. AB - A benign oropharyngial infection without appropriate treatment can be complicated by a jugular vein thrombosis and disseminated septic embolies with deleterious pulmonary effects. This septic clinical picture most commonly known as Lemierre syndrome is attributed to Fusobacterium necrophorum, a Gram negative anaerobic bacilli. We describe a case of a young patient who has presented this syndrome accompanied by typical pulmonary manifestations. Adequate antibiotic treatment for 3 weeks associated with anticoagulant treatment for about 3 months duration have allowed a complete recovery without sequel. PMID- 11217509 TI - [Symptomatic hypothalamo-hypophyseal metastasis revealing a small-cell bronchial carcinoma. Study of two cases]. AB - Metastases are an uncommon cause of tumor in the sellar region. We report two cases of small cell lung cancer presenting with visual loss and hypopituitarism resulting from metastasis to the pituitary area. PMID- 11217510 TI - [Massive hemoptysis during sarcoidosis]. AB - Hemoptysis is a rare but often severe event in sarcoidosis. It usually occurs in patients with advanced, fibrotic lung disease. We herein report the case of a 36 year old female patient with type II pulmonary sarcoidosis who presented with abundant hemoptysis very early during the course of her disease. Two attempts to embolize bronchial arteries remained unsuccessful and surgery was eventually required to stop the bleeding. Clinical, microbiological, radiological and pathological data indicate that haemoptysis was caused by systemic hypervascularization around sarcoidosis granuloma. PMID- 11217511 TI - [An unusual thoracic opacity]. AB - We report a case of a paraspinal meningocele in a 37-year-old man with no other clinical manifestation. The diagnosis was established on the basis of the computed tomography and magnetic resonance imaging features. PMID- 11217513 TI - [Depression: from practical aspects to theories]. PMID- 11217512 TI - [Indications for lung and heart -lung transplantation in adults. SPLF-SCTCVLF-EFG AFLM Lung Transplantation Group]. PMID- 11217514 TI - [Major depression. Clinical case]. PMID- 11217515 TI - [Major depression. Synthesis]. PMID- 11217516 TI - [Depression in eating disorders]. PMID- 11217517 TI - [Depression in the woman. Clinical case]. PMID- 11217518 TI - [Depression in the woman. Synthesis]. PMID- 11217519 TI - [Suicide with reference to age]. PMID- 11217520 TI - [Risk of suicide. Clinical case]. PMID- 11217521 TI - [Risk of suicide. Synthesis]. PMID- 11217522 TI - [Risk taking: a depressive equivalent?]. PMID- 11217523 TI - [The traps of neurotic depression]. PMID- 11217524 TI - [Depression in adolescence. Clinical case]. PMID- 11217525 TI - [Depression in adolescence. Synthesis]. PMID- 11217526 TI - [Physiopathologic hypotheses of depression]. PMID- 11217527 TI - [Depression after age 50. Clinical case]. PMID- 11217528 TI - [Depression after age 50. Synthesis]. PMID- 11217529 TI - [Evaluation methods of the efficacy of an antidepressive drug]. PMID- 11217530 TI - [Modalities for prescribing and taking antidepressive drugs. Clinical case]. PMID- 11217531 TI - [Modalities for prescribing and taking antidepressants. Synthesis]. PMID- 11217532 TI - [Defense and illustration of single case design in psychiatry]. PMID- 11217533 TI - [Prospective study of favorable factors in follow-up of drug addicted patients- apropos of 257 patients of the Cassini Center in Paris]. AB - Assessing the effectiveness of treatment is one of the main concerns of any medical process. The different ways proposed for assuming the responsibility of drug addicts and their efficacy are greatly heterogeneous since drug-abusing takes on diverse forms. Thus, in order to closely target the request of drug addicts and adjust their follow-up, we undertook to study prospectively, for 3 months, a population of drug addicts taking medical advice for the first time at the Cassini center in Paris, with the assumption that some predictors may forecast outcomes. METHOD: Data were obtained at the admission with a structured interview about socio-economic and demographic status, psychiatric disorders (assessed clinically according to DSM III-R and with HAD and MADRS scales), substance use and prior treatment history, environmental data (as well as familial substance use or support lending). Medical and paramedical referents have been interviewed after their first contact with the patient about his expectations and his motivation. Familial attendance at this first contact was noted as well as its implication in the programme. At the end of the study, we noted length of stay, regularity of follow up and clinical changes with a last interview of the staff. RESULTS: Half the time, patients' follow up doesn't last a month, drug abuse doesn't change in 6 out of 10 cases, and we only note 14% of durable abstinence. Polydrug abuse (over 80%) is not linked, here, with pejorative outcomes, in opposition to the usual literature. Heroin is the main substance used by our population (over 80%), other opiates, sedatives and alcohol are associated by more than 30% of these patients; cocaine is associated in a quarter of the cases. More than 10% of the patients are concerned by ecstasy and LSD. Cannabis use is common. Medical complaint (mainly viral diseases) at the beginning of the programme, concerns one of two patients. Only a few are initially known as being HIV positive, suggesting a great lack of information. Over forty percent of the patients are given a DSM III-R diagnosis at the end of the first medical advice, when a doubt subsists for a third of the other patients. Major depressive disorder for the first axis and borderline personality disorder for the second axis are the main disorders we founded. We also noted a large ratio (n = 13.5%) of schizophrenic disorders. Univariate analysis: length and regularity of the programmes are key factors of their efficacy. A long follow up is also required to improve patients' socio-economical status. Initial psychiatric disorders are linked, in our study as well as in literature, with longer stays in therapeutic programms. By revenge, psychiatric disorders at the third month (over 10%) are linked with poorer outcomes. We noted with interest that, in our sample, neither imprisonment in the past (over 40%, but we noted several imprisonments in a case out of two), or intraveinous route at any moment of the patient's life time (40%), or else a programm caused by a court (a quarter of the patients) are of wrong prognosis. Relatives' implication in the programm is linked with favorable outcomes. Multivariate analysis draws 3 independent clusters about the length of stay. One concerns patient's motivation as assessed by medical staff. An other one concerns patient's relatives' implication in the care. A third one is about the begining of the treatment: an initial medical prescrition and a psychological help are linked with favorable outcomes. About the efficacy, multivariate analysis isolates 4 independant clusters. Prior drug abuse programmes (one out of three patients) are associated with poorer outcomes, when, by revenge, familial relationship initially seen by the patient as (very) satisfying, patient's motivation, and, again, an initial medical prescription are linked with better outcomes. The study of those of the patients whose programme lasted more then 3 months but without any appreciable benefit shows that a long follow-up is successful when it is regular, when it provides a socio-economical status improvement and when the patient is given access to insight. For these patients, the (old) age is associated with better outcomes. By revenge, such a 3 months follow-up is not able to reduce drug abuse when a psychiatric disorder exists at the third month. Patients whose treatment was referred by a court don't differ from the others: their length of stay and outcomes are the same. DISCUSSION: Our study confirms our initial hypothesis according to witch subgroups in our population of drug abusers should be isolated and that some predictors of outcomes should be described. Three points seem important to be discussed. First, a medical prescription appears to be important to initiate the relationship between the patient and his practicioner. We have never see any report about this particular point. (ABSTRACT TRUNCATED) PMID- 11217534 TI - "Postpsychotic depression" and residual schizophrenia in a mental health hospital. AB - Forty three patients, mean age 55.20 +/- 9.27 SD, affected by Schizophrenia Residual Type (DSM IV, RDC criteria) and treated with neuroleptic drugs for a mean of 25.42 years (+/- 4.12 SD) were included into the study. Clinical evaluation was cross-sectional assessed by BPRScale, SAPS, SANS, HRS-D, EPSE. ACS and MMSE. Seventy percent of patients presented a "postpsychotic depression" (42%, mild; 16%, moderate and 12% serious). "Postpsychotic depression" does not seem to be influenced by neuroleptics, but it seems to be a component of residual schizophrenia in patients with a long lasting permanence in a mental hospital. PMID- 11217535 TI - [Validation of the French translation and factorial structure of the Tiffany and Drobes Smoking Urge Questionnaire]. AB - Over the past 10 years researches and clinicians have made substantial progress in understanding and treating nicotine dependence. To demonstrate the effectiveness of these treatments, reliable and sensitive measures of change and outcome must be used. In the nicotine dependence treatment literature numerous outcome have been used: frequencies drug use, problems associated with substance use, psychiatric comorbidity, withdrawal severity, and craving. The term craving reflects the subjective reports of addicts regarding their attempts to abstain from drug use and the state of their minds at the point at which they attempt to fail. Exposure to cues previously associated with nicotine play a role in precipitating relapse in eliciting a conditioned craving/withdrawal response and can be measures by the Questionnaire of Smoking Urge (QSU). OBJECTIVE OF THE STUDY: Validation in a French translated version of the QSU published in 1991 by Tiffany and Drobes. METHODOLOGY: 42 male and 62 female participated in the study with the translated questionnaire: mean age was 36.7 years, mean age at starting and mean duration of tobacco consumption was respectively 20.2 years old and 16.5 years, daily consumption was 16.6 cigarettes per day. The French translation of the QSU was administered to smokers instructed to abstain from smoking one hour and a half to three hours. RESULTS: The back translation has been accepted by Tiffany because more than 85% of the items are similar to the original questionnaire. We founded the same factor analysis with two factors, "desire to smoke" and "intention to smoke" accounting for 34% and 11% of the items variance, respectively. These two factors were the same than those of the original questionnaire. CONCLUSION: The validation of the French translation of the QSU gives the opportunity to use a sensitive instrument to assess craving. PMID- 11217536 TI - [Sleep polygraphy: diagnostic value in depressive pseudo-dementia. Attempt to improve visual scoring by digital periodic analysis]. AB - ARGUMENT: Pseudo depressive dementia is a common pathology for elderly patients. Classically, it is said that depression is taking the mask of dementia, but very often deterioration and depression are present at the same time. Sleep EEG can help the clinician to differentiate dementia and depression in pseudo depressive dementia. Slow Wave Sleep (SWS) is a good indicator of deterioration process. We tried to improve the sleep recording and analysis and our ability to differentiate SWS in this indication. We use a portable digital recording material (Hypnotrace). The signal is analysed by the association of a visual standard method to Digital Periodic Analysis (DPA) which is very sensitive to SWS. The visual analysis gives informations about the macroarchitecture of the night. The Digital Periodic Analysis gives at any moment the value of the wave frequency and thus informations about the microarchitecture. Our hypothesis is that this association helps to better recognise SWS and thus improves sleep EEG as a diagnostic tool in this indication. METHODS: 23 inpatients meeting both the criteria for major depression and dementia (DSM IV) have been recorded during two nights after 15 days of wash out and before antidepressant treatment. The recordings are analysed with the visual standard method and with the help of DPA. The patients are evaluated every 15 days during two months in order to define three groups based on the clinical evolution. RESULTS: The scoring with DPA is more sensitive to Slow Wave Sleep, particularly for the patients with good clinical evolution (with the strongest depressive component). Thus, this method could be a good diagnostic tool to differentiate dementia and depression in pseudo depressive dementia. PMID- 11217537 TI - [Cause of mortality in schizophrenic patients: prospective study of years of a cohort of 150 chronic schizophrenic patients]. AB - Overmortality in schizophrenic patients in comparison to the reference population has been found. At the present time this over mortality is mainly due to suicide or certain natural causes such as respiratory, cardio-vascular and cerebro vascular diseases. In France there are not psychiatric cas registers that could allow us to study the mortality of psychiatric patients. The aim of the study was first to determine the standardized mortality ratio (SMR) in a group of 150 chronic schizophrenics followed during 8 years and secondly to detect the variables that could predict this mortality. METHOD: The subjects filled out the RDC criteria for definite chronic schizophrenia and were included from 1991 to 1995. The subjects were inpatients or outpatients and their evaluation was made by psychiatrist. The subjects were selected from the different departments of two psychiatric hospitals corresponding to two French geographic areas (the Somme and Oise, two French "departement"). At the initial assessment socio-demographic, clinical and psychometrical variables were collected: sex, age, educative level, number of hospitalizations, mean duration of the illness, scores on the Physical Anhedonia Scale, Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale (PANSS). For the BPRS and PANSS, negative, positive and general subscales were extracted. In May 1999 all the subjects were contacted in order to know if they are alive or not and if they are death to know the date and the causes of their death. For the subjects that were still alive we used either direct assessment by interview of their psychiatrist or general practioner or indirect assessment by interview of their family. For the deceased subjects, we obtained informations about the date and the causes of the death by their psychiatrist or general practioner. If the patients were lost sight of we send a letter to the city of their place of birth in order to know if they are alive or not and if they are dead to know the date of their death. Moreover demographic data concerning the French and the Somme populations as well as the corresponding data concerning the mortality according to age and gender were obtained. A comparison of global mortality between patients and the French general or the Somme populations was made by the SMR. Moreover the deceased subjects and the survivors were compared by unidimensional statistical tests (chi 2 analyses for qualitative variables or Student's t test for quantitative variables) for the sociodemographic, clinical or psychometric variables. For each significant difference at p level < or = 0.05, the corresponding variable was retained for a multivariate step by step discriminant analysis. RESULTS: We found 13 deaths (10 males, 3 females): 3 suicides, 3 cardiac diseases, 2 cancers, 1 respiratory disease, 1 car crash, 1 homicide, 1 infectious disease, 1 respiratory arrest. The mortality rate (without correction for age) were 1.08% for both sexes, 1.44% and 0.6% for males and females respectively. The mortality rates (corrected for age) were 2.47% in our cohort and 0.988% in the Somme population. The corresponding SMR was 2.5. (chi 2 = 3.15, df = 1, p < 0.01). The overmortality was found only for males (chi 2 = 2.57, df = 1, p < 0.01) and not for females (chi 2 = 0.034, df = 1, p > 0.05). Concerning the comparisons between the deceased subjects and the survivors, there were five significant differences: gender, age, duration of the illness, neuroleptic dosage, negative symptoms (BPRS negative subscale). The deceased subjects were older, there was more men, the duration of the illness and the neuroleptic dosage were higher and the BPRS negative subscale was lower. These five variables were introduced in the discriminant analysis to explore notably their respecting weight. The corresponding power of the five variables were in decreasing order: neuroleptic dosage, negative symptoms, age, gender, duration of the illness. DISCUSSION: Our study confirm the overmortality in schizophrenic patients, this overmortality was especially explained by natural and non natural causes of death. The overmortality concerned only schizophrenic males patients whereas schizophrenic females did not have an overmortality. This negative result could be explain by a bias selection, the males being overrepresented in our cohort. Among the variables that were linked to the overmortality, the low level of negative symptomatology confirmed previous studies that have shown a low suicide rate in deficit schizophrenic. Moreover a high level of positive symptomatology could lead to high risk behaviors (suicide attempts, sexual disinhibition...). The neuroleptic dosage was the variable whom discriminate power was the highest. At least two explanations can be proposed. (ABSTRACT TRUNCATED) PMID- 11217538 TI - [Biological markers in schizotypal and borderline personality disorders]. AB - A preliminary but growing body of evidence supports the existence of biological substrates in personality disorders. Based on a review of the literature, the article deals with the major biological markers: genetic, cognitive, biochemical, electrophysiological and organic markers, of schizotypal and borderline personality disorders. In addition, the article compares these findings in these two types of pathological personality. In the field of genetics, we notice several indices in favour of a relationship between schizotypal personality disorder (SPD) and chronic schizophrenia. In contrast, in borderline personality disorder (BPD), indices were lacking for such a relationship between this disorder and one of the axis I diagnosis, or a clear genetic transmission. In the field of cognitive tests, we can note in both SPD and BPD, that the abnormalities which would be at the level of temporal and frontal lobes, may be implicated in the observable cognitive troubles in these two disorders. In the field of neurobiochemistry, the dopaminergic and serotonergic systems seem to be implicated in the etiology of SPD while several data point out the fact that several neurotransmitter systems (dopaminergic, serotonergic, noradrenergic and cholinergic) seem to be involved in the etiology of BPD. Finally, in the field of electrophysiology, we notice that some of these tests observed in SPD (smooth pursuit eye movements, evoked potentials, modification of the electrodermic response) seem reinforcing the relationship between SPD and schizophrenia while those observed in BPD seem reinforcing either a relationship between BPD and depression (sleep studies), or a relationship between BPD and schizophrenia (evoked potentials, smooth pursuit eye movements). PMID- 11217539 TI - [Biological factors of post-traumatic stress: neuroendocrine aspects]. AB - The core symptoms of post-traumatic stress disorder (PTSD) include persistent reexperiencing of the traumatic event, avoidance of stimuli associated with the trauma, and autonomic hyperarousal. Many neurotransmitter systems and neurobiologic mechanisms may account for these primary symptoms of PTSD. Severe psychological trauma results in the parallel activation of these systems, producing an array of adaptive behavioral and physiologic responses necessary for survival. The pathophysiology of PTSD may involve dysfunction of several brain structures, particularly the amygdala, locus coeruleus, and hippocampus, as well as noradrenergic system and hypothalamic-pituitary-adrenal (HPA) axis. The neuroendocrinology of PTSD, and specifically hypothalamic-pituitary-adrenal axis alterations, are ways of examining biologic heterogeneity following trauma and its possible clinical implications. The decreased levels of cortisol, the increased responsiveness of glucocorticoid receptors, the increased sensitivity of the HPA negative feedback inhibition and its progressive sensitization are the neuroendocrine alterations specifically associated with the development of PTSD. PMID- 11217540 TI - [Antipsychotic drugs and cardiovascular safety: current studies of prolonged QT interval and risk of ventricular arrhythmia]. AB - Cardiovascular mortality is higher among schizophrenic patients than in the general population, and it is possible that most unexplained sudden deaths among these patients are due to ventricular arrhythmias for which antipsychotic drugs are either the cause or a predisposing factor. Most antipsychotic agents show electrophysiological effects resembling those of class 1a antiarrhythmic agents, and may be responsible for prolonging the QT interval, potentially going on to cause torsades de pointes. Some of the antipsychotic agents carry a high risk of arrhythmias, related to their effects on the QT interval. These include thioridazine, pimozide, sultopride, droperidol, and to a lesser extent haloperidol and chlorpromazine. In the case of the new atypical antipsychotic agents, it is possible to rank the risks of different drugs, with sertindole (now withdrawn from sale) having the highest risk, and ziprasidone somewhat lower, followed by risperidone and finally by quetiapine, clozapine and olanzapine which have negligible effects on the QT interval. A number of risk factors have been demonstrated, particularly: hypokalaemia and hypomagnesaemia, bradycardia, congenital long QT syndrome, and any underlying cardiac pathology. Lastly, the risk associated with any given antipsychotic agent is increased if it is combined either with any other drug known to prolong the QT interval and provoke torsades de pointes, or with any drug capable of inhibiting the hepatic metabolism of the antipsychotic agent. A list of such drugs is provided, together with advice on the action to be taken when prescribing an antipsychotic agent to a patient with a long QT interval. PMID- 11217541 TI - [Prospective follow-up over a 12 month period of a cohort of 155 patients with obsessive-compulsive disorder: phase III National DRT-TOC Study]. AB - In the phase III of the french national study on OCD, 155 patients suffering from an OCD (full DSM III-R criteria, score on NIMH-OC > or = 7, not treated or undertreated) had entered a naturalistic follow-up of 12 months duration. Obsessions, compulsions, depression, anxiety, impulsivity and global functioning were assessed by using NIMH-OC, CPRS-OC2, MOCI, MADRS, HAD (-A, -D), BDS (Behavioral Dyscontrol Scale), CGI and GAS (DSM III-R). From the initial population (155 patients), 130 (84%) had been treated with drugs and were "completers" and assessed at M6 and M12; 18 (11.6%) were lost to follow-up and 7 (4.5%) had dropped out because of treatment refusal, side-effect or improvement. Only 19% of patients had received a behavior therapy. In spite of selection of patients with severe and chronic OCD associated to depression (mean MADRS score = 25), 85% of treated patients had been treated with one anti-OCD drug (105 with fluoxetine, 17 with clomipramine and 17 with other antidepressants), 4.5% needed a treatment substitution and 4.5% a bitherapy (combination of 2 anti-OCD drugs); 84% of patients were considered as "good compliant" with visit agenda and treatment. At the end of follow-up, global improvement was observed in 77% of patients treated. Clinical improvement was assessed by different response criteria (final NIMH-OC score, 30% decrease on NIMH-OC, 35% decrease on MOCI, final GAF score > or = 70) which showed 4 patterns of response to treatment: "positive response on M6 and M12" = 43-64%; "only M12" (slow response) = 13-24%; "only M6" (escape or relapse) = 4-6%; "negative response on M6 and M12" (resistant OCD) = 19-33%. During 12 month treatment, 31 patients (22.5%) had presented an adverse effect in which 7 cases (5.1%) with "serious adverse event" and 5 cases (3.6%) who required treatment drop-out. Predictive factors of clinical response to anti-OCD drugs were explored: 1) "lack of insight" was the best factor to characterise the resistant group; 2) high base-line of "impulsivity" predict better response at M6; 3) important to severe slowness was associated with a longer delay to response (between M6 and M12). The results of the phase III from the french multi-site study will be compared to the international data on long-term treatment of OCD. PMID- 11217542 TI - [Apropos of using patient isolation in psychiatry: point of view of nurses]. AB - Seclusion continues to be used in the care of acutely disturbed psychiatric patients despite often emotionally charged debate about its appropriateness within mental health services. Powerful legal and moral arguments about the use of seclusion emphasize an urgent need to critically examine its role in the care of mentally ill people. This paper examines the use of seclusion on psychiatric departments in the management of acutely disturbed patients: 36 psychiatric nurses working in 6 departments in a specialized hospital (the CHS de la Savoie, in Chambery) were interviewed in relation to their perceptions of the role of seclusion. Data were analysed using grounded theory methodology revealing the core conceptual category "controlling" and two sub-categories "watching out for" and "watching over". Seclusion was found to be used as an adjunctive treatment in the care of individuals considered to be "out of control". Clinicians expressed comfort with the use of seclusion, citing a strict protocol that provided parameters for its use. While expert therapeutic interventions were described by clinicians, they are contextualized within a framework of power and control--a framework that stands in stark contrast to contemporary philosophies of nursing care, providing impetus for a reconsideration of the use of constraining practices in the care of mentally ill people. PMID- 11217543 TI - [Weight gain and antipsychotic drug treatment]. AB - Like the classical neuroleptic drugs, most of the new antipsychotic agents can cause weight gain in patients receiving long-term treatment. However, it remains difficult to rank the different compounds according to their propensity to cause this unwanted side-effect. Recent data suggest that weight gain appears to be essentially related to an increase in appetite in these patients. Thus, it is a fact that the patients' diet represents the main predictive factor for weight gain, independently of the antipsychotic compound prescribed. In contrast to the other and often more disabling side-effects of these treatments, overweight can be effectively prevented by simple hygienic and dietetic measures. It would therefore be advisable to discuss the possibility of this side-effect of antipsychotic treatment with the patient, and to suggest appropriate preventive measures, as part of the therapeutic partnership. PMID- 11217544 TI - [Varicocele in adolescents]. AB - Varicocele is a frequent disease in adolescents (15%) and has a harmful effect on growth of the testis and spermatogenesis, which deteriorates with increasing exposure time to varicocele. However, only 15 to 20% of adults with varicocele are infertile. It is currently impossible to predict, among adolescents with a varicocele, those who will subsequently be infertile. Testicular hypotrophy reflects testicular repercussions, but its correlation with subsequent infertility is unknown at the present time. However, treatment of varicocele allows correction of testicular hypotrophy. Although the arguments are still only speculative, testicular hypotrophy, together with symptomatic and/or grade III varicocele, represents a logical indication for treatment of varicocele in adolescents. Many techniques can be used to occlude the varicocele in adolescents. Open retroperitoneal surgery is currently the reference method. PMID- 11217545 TI - [High intensity focused ultrasound (HIFU) in urology]. AB - INTRODUCTION: Focused ultrasound is now well known to urologists in the context of its validated application in extracorporeal lithotripsy. High Intensity Focused Ultrasound (HIFU) represents a potential therapeutic modality for tissue destruction due to its very high energy and its capacity to precisely reach a target with a very short emission time. The authors review the current state of art of HIFU in urology at a time when its indication in prostate cancer is being defined. MATERIAL AND METHOD: After a brief description of the main physical principles of ultrasound and the main data determining focussing of high energy ultrasound, the main machines available (research and clinical) are described. The published clinical literature concerning the tissue destructive action in urology is reviewed. RESULTS: HIFU has been used in urology to treat renal, vesical, prostatic (BPH and cancer), and external genital organ lesions. Purely extracorporeal machines are gradually being replaced by intracorporeal procedures, especially transrectal techniques for prostatic lesions. The quality of ultrasound detection of the target still limits the use of this minimally invasive modality. The intervening tissues are spared with a good therapeutic efficacy on the target tissues, provided optimal firing parameters are used. CONCLUSION: HIFU has a demonstrated potential in the treatment of prostate cancer and studies conducted by several teams have defined the technique and its efficacy. Other indications have been studied, but must be validated by further clinical trials. The future will probably see the design of machines adapted to a specific target tissue rather than a single multidisciplinary extracorporeal machine. PMID- 11217546 TI - [Mechanisms of action of BCG: towards a new individualized therapeutic approach?]. AB - A better knowledge of antitumour immunity and the mechanisms allowing the tumour to overcome the host's immune surveillance has led to progress in the understanding of the mechanisms of action of Bacille Calmette-Guerin (BCG), as the local intravesical immune response is intimately related to the interaction of three systems: the host (the patient), the BCG (mycobacteria) and the tumour. This interaction gives rise to a cascade of immunological events, some of which are essential to the protective action of BCG against relapse and tumour progression. The immune response to BCG is currently considered to comprise three phases. First of all, the BCG adheres to the urothelium and is then phagocytosed by antigen-presenting cells. This phase corresponds to early release of so-called inflammatory cytokines (IL1, IL6, IL8). These cytokines could be responsible for certain adverse effects, but could also participate in cytotoxic phenomena. The second phase consists of recognition of bacterial antigens by helper CD4 lymphocytes, which mainly release IL2 and IFNg (Th1 response). This cellular activation leads to the third phase: amplification of cytotoxic populations capable of killing tumour cells: CD8, gd lymphocytes, macrophages, NK, LAK, BAK cells. All these cells also produce cytokines, which participate in regulation of the immune response. The understanding of these mechanisms of action, urinary cytokine assays, a better definition of cytotoxic cells and their role, molecular analysis of the tumour and probably certain genetic characteristics of the host will allow the elaboration of more effective immunization protocols by defining an individualized therapeutic approach. PMID- 11217547 TI - [Kidney harvesting in living donors with manually assisted laparoscopy: technique and results]. AB - OBJECTIVE: To evaluate the feasibility and complications of manually assisted laparoscopic live donor kidney harvesting. MATERIAL AND METHOD: Since June 1999, all related live donor kidney harvests have been performed by manually assisted laparoscopy. The patient is placed in the lumbotomy position and an 8 cm midline periumbilical incision is made. The assistant's hand is introduced through a watertight port (HandPort). Three trocars are used. The assistant presents the structures to be dissected and controls the ureter. The artery is clipped and the vein is stapled or clipped, depending on its diameter. The kidney is extracted via the midline incision and washed. RESULTS: Five kidney harvests were performed (three right kidneys and two left kidneys) with a mean operating time of 220 +/- 30 minutes. Conversion was necessary in one case following the intraoperative discovery of two right renal veins. Warm ischaemia lasted 5 minutes for the first patient and one to two minutes for the other four non-converted patients. Blood losses were minimal. The mean duration of major analgesia was 2.4 days and the mean length of hospital stay was 7.2 days. Complications were: bacteriuria in 2 cases and prolonged lymphorrhoea in 1 case. One transplanted kidney had to be removed because of immediate thrombosis of the recipient iliac artery. With a mean follow-up of 6 months (1 to 12 months), no ureteric or venous complications have been observed in the 4 evaluable transplanted kidneys. CONCLUSION: An intra abdominal hand during laparoscopic live donor kidney harvesting simplifies dissection, ensures intraoperative security and allows rapid extraction of the kidney. PMID- 11217548 TI - [Balloon catheter parieto-renal dilatation in percutaneous kidney surgery]. AB - OBJECTIVE: To compare two techniques of parieto-renal dilatation for percutaneous surgery: Alken dilators and balloon catheter. MATERIAL AND METHODS: This prospective, non-randomized study was conducted between July 1999 and April 2000 in 20 patients undergoing percutaneous renal surgery. 10 patients were dilated with a balloon catheter (NephroMax, Boston Scientific) and the other 10 patients were dilated with Alken metal dilators. Statistical analysis was performed with the Mann-Whitney test. RESULT: The dilatation time and x-ray exposure time were shorter during balloon catheter dilatation (statistically significant difference) and the two techniques were associated with a comparable morbidity. CONCLUSION: Balloon catheter parieto-renal dilatation significantly decrease dilatation and x ray exposure times and very considerably simplifies this operative step, essential to the success of percutaneous surgery. PMID- 11217549 TI - [Cystine lithiasis: study of a series of 116 cases]. AB - INTRODUCTION: Cystine stones is a rare disease, related to a genetic metabolic disease. Its management must treat both the stones and their complications, and prevent recurrences by controlling cystinuria. OBJECTIVE: The objective of this study was to define the natural history of cystine stones, identify reliable diagnostic criteria and propose a simple treatment regimen. MATERIAL AND METHOD: The authors studied the clinical, biochemical and radiological data of a retrospective series of 116 cases, treated by the same urologist between 1953 and 1999. RESULTS: Cystinuria is often diagnosed in young adults on the basis of urine biochemistry (Brand's reaction, urinary cystine assay) or spectrophotometric analysis of the stones or urinary crystals. This assessment, not performed routinely, must be guided by a family history, recurrent stones or following failure of lithotripsy. The appearance of the stones, macroscopically a waxy yellow, radiologically only slightly opaque with a large component in the renal pelvis associated with a small round caliceal stones, is highly suggestive. Radiological assessment by IVU is generally sufficient. Treatment of the disease is medical and surgical: dietary measures, alkalinization of the urine and possibly drug treatments, are associated with extracorporeal lithotripsy or surgical treatment. These modalities eliminate cystine stones in 70% of cases. Recurrent stones are observed in 42% of cases followed for more than 5 years, mainly due to the presence of residual fragments (60% of recurrences). Surveillance and dietary measures must be maintained for life. Surveillance is based on biannual radiographic follow-up (plain x-rays +/- ultrasound) to detect and consequently treat small stones. A test for cystinuria must be proposed to all relatives of affected patients. CONCLUSION: This disease presents very polymorphic clinical features and clinical course. It can be responsible for impaired renal function and must therefore be investigated in the presence of suggestive clinical signs or history to avoid a delayed diagnosis, as treatment modalities are available to decrease the frequency of recurrence and which can potentiate treatment by surgical or lithotripsy. However, there are no predictive factors of deterioration of the disease, and biannual surveillance, for life, is essential to detect and treat small stones. PMID- 11217550 TI - [CT-guided percutaneous fine needle biopsy of solid tumors of the kidney]. AB - OBJECTIVE: This study was designed to evaluate the reliability and the role of percutaneous needle biopsy in the diagnosis of renal masses. MATERIALS AND METHODS: 85 biopsies were performed in 74 patients (mean age: 62 +/- 14 years). The median tumour diameter was 4.44 +/- 2.53 cm. Biopsies were performed with an 18G ASAP* needle with CT guidance. 2 to 4 cores were obtained per patients. All biopsies were performed as an outpatient procedure. RESULTS: Biopsies were uninterpretable in 15 cases (17%) (13 with normal or no renal tissue and 2 necrotic samples). A benign lesion was detected in 8 cases (4 fibrous lesions, 4 infectious lesions). In 3 cases, biopsies were suspicious of cancer, which was confirmed on definitive histology. In 59 cases, biopsies were neoplastic: 6 benign tumours (4 oncocytomas, 1 angiomyolipoma, 1 cystadenoma), 42 renal cell carcinomas (RCC) (conventional: 32, chromophobe: 3, tubulopapillary: 7), 5 urothelial carcinomas, 3 metastases, 2 lymphomas and 1 sarcoma. The median Furhman grade was 2. 30 RCC were operated. The correlation coefficient for the biopsy and pathology histological type was 0.90. The median pathological Furhman grade was 2. The biopsy results modified therapeutic management in 38% of cases. There was no morbidity, post-biopsy medical management was never required. CONCLUSION: Biopsy of renal masses is reliable for evaluation of the histological type. The introduction of the CT scope should increase the accuracy of biopsies. The morbidity is low compared to that of diagnostic surgery. PMID- 11217551 TI - [Hydroposturotherapy and residual lithiasis after lithotripsy]. AB - OBJECTIVE: The authors report the results of hydroposturotherapy on elimination of residual stone fragments after extracorporeal lithotripsy. MATERIALS AND METHODS: 417 subjects with residual stone fragments after one or several lithotripsy sessions, who failed to eliminate any fragments over a period of 3 to 6 months, or even 12 months, before starting treatment, were submitted to intensive water intake and appropriate daily hydrotherapy. Hydrotherapy was adapted to each case and, in the case of residual lower caliceal stones, the subjects were placed in the vertical position, head downwards with the feet in the air, to facilitate migration of stone fragments. RESULTS: The subjects examined their urine at each micturition and collected any fragments expelled. Overall, in the population of 417 subjects treated in this way for three weeks, partial or complete expulsion was obtained in 282 cases (67.6%). Stone expulsion was obtained in 218 of the 305 cases (71.5%) of residual lower caliceal stones and 64 of the 112 cases (57.1%) of middle or upper caliceal stones. Stone expulsion, when obtained, usually started by the first, second or third day of treatment. CONCLUSION: This study shows that hydroposturotherapy can improve the elimination of residual stone fragments following extracorporeal lithotripsy. PMID- 11217552 TI - [Ureteral lesions after surgery of the aortic bifurcation. Report of 6 cases]. AB - OBJECTIVE: The objective of this study was to evaluate the management and current treatment options for ureteric complications after vascular surgery based on a series of 6 cases. PATIENTS AND METHOD: 6 patients were treated between 1990 and 1998 (mean age: 64.7 years) for ureteric complications after aortic bifurcation surgery. The mean interval between vascular surgery and urological management was 11.6 years (+/- 4.04). All patients were assessed by intravenous urography (IVU), and 4 patients were assessed by abdominal computed tomography (CT). These complications consisted of: 2 cases of ureteric stenosis, 1 case of inflammatory peri-ureteritis, 2 cases of chronic peri-ureteritis and 1 case of compression by a false aneurysm. The lesion was situated in the iliac ureter in every case. RESULTS: Treatment consisted of temporary double J stenting (n = 1), ureter release (n = 1), endoscopic dilatation (n = 1), psoas bladder reconstruction (n = 1) and corticosteroid therapy (n = 2), with 4 successes, 1 failure (corticosteroid therapy), and 1 death from another cause. CONCLUSION: Ureteric lesion after vascular surgery is a rare complication, often discovered incidentally. The iliac ureter is predominantly affected. IVU and CT are the reference examinations. Treatment options primarily depend on the patient's general state. PMID- 11217553 TI - [In vitro study of the modulation of human ureteral tonus by nitric oxide and zaprinast, a phosphodiesterase inhibitor]. AB - AIM OF THE STUDY: To assess the role of nitric oxide (NO) and its second messenger, cGMP, on the mechanisms underlying human ureteral smooth muscle relaxation. METHODS: Proximal segments of ureter were dissected from nephrectomy, then cut into rings and suspended in organ chambers. Isometric tone was recorded at baseline and after preincubation with KCl (120 mumol). The Increasing concentration (10-8-10-4 M) of NO donors, Sodium nitroprusside, (SNP) and molsidomine (SIN-1) and a type V phosphodiesterase inhibitor, Zaprinast were added to the organ chambers and a dose response curve was constructed from each experiment. RESULTS: Dose-dependent relaxation was seen with all compounds. This was, however, more pronounced with SNP as compared with SIN-1. Zaprinast alone had marginal relaxant effect but markedly potentiated the relaxing effect of the NO donor SNP (p < 0.05). Inhibition of NO synthesis by the arginine analogue L-NA increased electrical-induced contraction (98 +/- 4% vs 122 +/- 3%, p < 0.001). CONCLUSION: Activation of the soluble guanylate cyclase by NO donors markedly relaxed significantly human ureteral smooth muscle but inhibition of phosphodiesterase did not affect the in vitro relaxation. Our results suggest that cGMP is an important second messenger in the transduction signalling pathway leading to relaxation of human ureteral smooth muscle. By contrast, basal activity of phosphodiesterase seems to be marginal under physiological condition. PMID- 11217554 TI - [Pfannenstiel short horizontal laparotomy in retropubic radical prostatectomy]. AB - OBJECTIVE: To evaluate the feasibility of the Pfannenstiel short horizontal laparotomy to perform retropubic radical prostatectomy and its consequences on postoperative analgesic consumption. MATERIALS AND METHODS: From December 1998 to February 2000, 62 radical prostatectomies were performed via a short horizontal suprapubic incision. The mean length of the incision in the lower abdominal fold was 10.2 cm (range: 8 to 14 cm). The mean duration of radical prostatectomy was 130 minutes (range: 90 to 210 min). Double drainage (retropubic and subaponeurotic) was systematically maintained for an average of 48 hours. Postoperative narcotic analgesic consumption, and the modalities and duration of prescription were compared between 30 patients operated by this technique and 30 patients previously operated via a midline infraumbilical incision. RESULTS: The abdominal wall opening and closing time was about 20 minutes. The operation was always performed via this incision, allowing excellent exposure of lymph node areas and the prostate. Postoperative complications related to this incision consisted of a single subaponeurotic haematoma, which was not drained. The mean dosage and duration of postoperative analgesic consumption decreased by 44% compared to the reference group. Postoperative assessment of the abdominal wall showed almost complete disappearance of the scar at 3 months and no secondary wound dehiscence. CONCLUSION: The Pfannenstiel short horizontal laparotomy is a simple and reproducible technique for retropubic radical prostatectomy. This feasibility study was accompanied by a reduction of postoperative analgesic consumption in the study group. PMID- 11217555 TI - [Vesico-uterine fistula. Report of 10 cases]. AB - OBJECTIVE: To study the aetiopathogenics, diagnostic and therapeutic aspects of this pathology. MATERIALS AND METHODS: The authors report a series of 10 vesico uterine fistulas observed over a 10 years period. The mean age was 32 years(30 40). The fistulas were secondary to cesarian section in 6 cases and to abnormal delivery in 4 cases. The symptomatology was an urinary leakage from the vagina in 6 cases, an isolated cyclic hematuria in 3 cases and the association of the two signs in one case. The diagnostic was established on clinical examination in 8 cases. Intraveinous urography was performed in all the patients and visualised the uterine cavity in only 8 cases. In the 2 remaining cases a retrograd cystography was performed and demonstrated the opacification of the uterine cavity. The treatment was surgical in 9 cases. One patient who had a menuria has refused the operation. RESULTS: The diagnostic of the vesico-uterine fistulas is often based on clinic examination but often necessitate recourse to complementary examinations mostly in the menouria forms. The intraveinous urography does not establish the diagnostic in all the cases but is an indispensable complementary investigation because it permits searching for an associated ureteral injury. With a mean recoil of one year the results judged on the disappearance of the clinic signs was good in all the patients. CONCLUSION: The vesico-uterine fistulas are often secondary to cesarian section or abnormal delivery. Their treatment is surgical but is above all preventive by the improvement of the obstetric taking care and avoiding the vesical injuries in the course of the cesarian section. PMID- 11217556 TI - [Assessment of hemorrhage risk of transvesical prostatectomy with bladder neck cerclage]. AB - OBJECTIVE: Evaluation of blood loss and predictive factors of haemorrhagic complications of transvesical prostatectomy. MATERIAL AND METHODS: From January 1994 to December 1998, 202 patients with a mean age of 70.5 +/- 7.4 years (range: 46.6-89.3 years) were operated for benign prostatic hyperplasia with a mean prostate weight of 86 +/- 33 g. Transvesical prostatectomy was performed with bladder neck cerclage and suction drainage of the prostatectomy site for 48 hours. 107 patients donated blood preoperatively (mean: 2.8 +/- 0.7 units) to allow possible autotransfusion. Blood losses were evaluated by determining haematocrit during hospitalisation, the quantity of blood collected intraoperatively and the presence of postoperative bleeding possibly requiring surgical revision. RESULTS: The calculated overall blood loss was 435 +/- 306 ml of RBC, i.e. 1783 ml for an haematocrit of 30%. A high ASA score was significantly related with higher blood loss and preoperative anticoagulant treatment. No predictive factor for intraoperative bleeding (mean: 519 +/- 327 ml) was identified. Absence of the median lobe and a high ASA score were also predictive factors of postoperative bleeding. Age, operating time, prostate weight, recent urinary tract infection, preoperative drainage, preoperative haematocrit, and preoperative blood donation (autotransfusion) did not significantly influence the volume of blood loss. CONCLUSION: Apart from the ASA score, no predictive factor for the severity of bleeding associated with transvesical prostatectomy was defined in order to identify a group of patients at higher risk of severe bleeding. PMID- 11217558 TI - [Fluorodeoxyglucose (FDO) positron emission tomography (PET) in testicular germ cell tumors in adults: preliminary French clinical evaluation, development of the technique and its clinical applications]. AB - OBJECTIVES: Metabolic positron emission tomography (PET) is a new imaging modality for the detection of tumours, which uses fluorodeoxyglucose (FDG) to demonstrate increased carbohydrate metabolism of malignant cells. The management of testicular germ cell tumours in adults raises three clinical problems poorly resolved by conventional imaging techniques: identification of suspected recurrences in a context of elevated circulating serum markers, initial staging assessment after orchidectomy, evaluation of the response to treatment. MATERIAL AND METHODS: The authors report the data obtained in 16 patients (6 cases of seminoma and 10 cases of non seminomatous germ cell tumour [NSGCT]), investigated in the Frederic-Joliot Department using a dedicated PET camera, 60 minutes after intravenous injection of 270 MBq of FDG. RESULTS: In 9 cases of assessment of elevated serum markers with no tumour identified by conventional examinations, PET demonstrated images likely to correspond to tumour sites in 7 patients (5 true-positives [TP] and 2 false-positives [FP] due to postoperative inflammatory changes). PET was negative in 2 out of 9 patients, in whom subsequent follow-up showed spontaneous but delayed return to normal of tumour markers. In 3 of the 4 cases of initial staging of the disease, PET excluded an extension suspected by conventional imaging and the 4th case was a FP for PET. In 3 cases of evaluation of the response to treatment, PET concluded on the absence of viable residual tumour mass, with a false-negative result in one case. CONCLUSIONS: These results are in line with those reported in the literature, which emphasize the diagnostic difficulties encountered in this disease. The significant contribution of FDG-PET should be confirmed by larger series of patients investigated by this new modality. PMID- 11217557 TI - [Prospective, multicentric, open, and controlled evaluation of the effectiveness of prostatron 2.5 in the treatment of prostatic benign hypertrophy: 1-year results]. AB - OBJECTIVE: Evaluation of the efficacy at 1 year of the Prostatron 2.5 in the treatment of BPH weighing more than 40 grams. MATERIAL AND METHODS: 46 patients over the age of 50 years presenting with BPH > 40 grams responsible for a maximum flow rate (MFR) < 9 ml/s and a mean IPSS score of 18 were prospectively included without randomization, by 5 French Urological Centres. These patients were reviewed at 3, 6 and 12 months. Primary endpoint: MFR; secondary endpoints: Madsen score and IPSS. RESULTS: No major complications were observed. The mean postoperative catheterization time was 10 days, causing discomfort with a mean score of 5 on a visual analogue scale from 0 to 10.. Maximum flow rate waas 13.4 ML/s at 3 months, 13.4 ml/s at 6 months and 14.7 ml/s at 12 months. The IPSS was improved by 75%. CONCLUSION: Treatment by Prostatron 2.5 improves the MFR and the patient's quality of life, which is maintained for at least 1 year after treatment. PMID- 11217559 TI - [Epidermoid cancer of the kidney pelvis]. AB - Squamous cell carcinoma of the renal pelvis is a rare tumour, mainly occurring in elderly patients with neglected and secondarily infected pyelocaliceal stones. It has a poor prognosis. The authors report the case of a 74-year old man with a destroyed and painful kidney containing a staghorn calculus for 30 years. The preoperative diagnosis was pyonephrosis, but nephrectomy, justified by the symptoms, showed that the kidney was invaded by a squamous cell carcinoma of the renal pelvis invading the psoas. The patient died 1 month after the operation. Treatment is essentially preventive by removal of staghorn calculi and management of chronic urinary tract infections. PMID- 11217560 TI - [Urothelial tumor and colonic cancer in the context of a syndrome of hereditary predisposition to HNPCC colonic cancer]. AB - The authors report the association of ureteric tumour and colon carcinomas in the context of hereditary predisposition to HNPCC colon cancer (hereditary non polyposis colon cancer). The recall the diagnostic criteria of HNPCC syndrome and emphasize the importance of guiding the clinical interview of patients with upper urinary tract tumours in order to detect a family history and the presence of gastrointestinal tumours. PMID- 11217561 TI - [Primary lymphoma of the bladder]. AB - The authors report two cases of primary non-Hodgkin's malignant lymphoma of the bladder. In contra with secondary site, which are not rare, primary malignant lymphomas of the bladder wall are exceptional. Urinary symptoms are varied and nonspecific. These tumours cannot be distinguished from other bladder tumours on the basis of their radiological or endoscopic appearance. Only histology provides the diagnosis. The pathophysiological hypotheses are discussed. Treatment is mainly based on chemotherapy. Endoscopic drainage procedures are sometimes useful, as in one of the reported cases. PMID- 11217562 TI - [Rupture of the female urethra in pelvic fractures: report of 2 cases]. AB - Urethral trauma after fracture of the pelvis is rare in women due to the mobility and short length of the urethra, which is consequently better protected in the case of trauma than the male urethra. Vaginal trauma is sometimes associated due to the intimate contact between the urethra and vagina. A pelvic and perineal examination must be systematically performed in all women presenting with pelvic trauma to avoid the morbidity resulting from late diagnosis of urethral trauma. Early surgical operation allows precise repair of the lesions, ensuring a good functional result. PMID- 11217563 TI - [Cancer of the female urethra. Report of 2 new cases]. AB - Female urethral cancer is a rare urologic malignancy, it is about 0.02% of genito urinary cancer in woman. Prognosis remains poor and it depends of staging of disease. Applying combined modality treatment (radiation and surgery) may produce local control and increase the survival. PMID- 11217564 TI - [Primary mucinous carcinoma of the female ureter]. AB - The authors report a new case of primary mucinous carcinoma of the urethral meatus in a 66-year-old patient, treated by simple excision. The patient is in very good general health one year after the diagnosis. Although primary mucinous carcinoma of the female urethra is very rare, this diagnosis should be considered in any case of macroscopically suspicious urethral polyp, after having eliminated a gastrointestinal, vesical or gynaecological origin. Only seventeen cases have been published in the literature. Unlike our case, most of the reported lesions involved all of the urethra at the time of diagnosis and frequently presented extension to periurethral tissues or adjacent organs. A very poor prognosis is reported in the literature, even despite treatment, based on surgery and/or radiotherapy. PMID- 11217565 TI - [Progression of stage I non-seminomatous germ cell tumors during surveillance. Role of positron emission tomography]. AB - Surveillance is one of the options proposed in the management of stage 1 non seminomatous germ cell tumours when there is only a low risk of progression. No consensus has yet been reached concerning the modalities of this surveillance and several protocols are available, including the CCAFU protocol. The presence of recurrences in this population at low risk of progression, estimated to be 5%, accounts for the continuing research for more precise predictive factors of occult metastases. Although several studies appear to indicate a useful predictive value for some of these factors, their application in clinical practice still appears to be difficult. PET metabolic imaging (positron emission tomography) could constitute a new approach to staging of these tumours, allowing the detection of tumour sites by an increase of carbohydrate metabolism of malignant cells. However, no study is yet available to define the real place of this technique. PMID- 11217566 TI - [Unusual tumor: liposarcoma of the spermatic cord]. AB - Spermatic cord liposarcoma is a rare tumour, as only 60 cases have been reported in the literature. They represent 7% of all malignant spermatic cord tumours. The authors report a new case of spermatic cord liposarcoma unusual by its inflammatory and fibrotic features, occurring in an 83-year-old man in poor general health. Treatment consists of surgical resection as widely as possible. Adjuvant radiotherapy is sometimes effective on local recurrences. Despite the slow rate of progression of this tumour, prolonged surveillance is required due to the high risk of late recurrence. PMID- 11217567 TI - [Paratesticular rhabdomyosarcoma]. AB - The authors report a case of embryonal paratesticular rhabdomyosarcoma in a 9 year-old child and discuss the treatment modalities in the light of data from the literature. PMID- 11217568 TI - [Malignant testicular non-Hodgkin's lymphoma in a young subject]. AB - The authors report a rare case of testicular non-Hodgkin's malignant lymphoma (NHML) in a 21-year-old man with a fatal outcome. In the light of the literature, they analyse the clinical features, clinical course and treatment of this lymphoma. PMID- 11217569 TI - [Materials used in treatment of stress urinary incontinence with suburethral sling]. AB - Suburethral sling is a classical method of surgical repair of female stress urinary incontinence (SUI). Initially reserved for SUI due to sphincter incompetence, this method now appears to be indicated for other types of SUI. A large number of organic and synthetic materials have been used in published series. The long-term functional results reported in the literature vary between 65 and 98%, regardless of the materials used. Some of the complications observed are specific to the type of material. Synthetic slings appear to be associated with a higher complication rate. It is too early, based on data of the literature, to determine the real role of Prolene tape (TVT). PMID- 11217570 TI - [Extra-corporeal lithotripsy in children]. AB - Extracorporeal shock-wave lithotripsy (ESWL) constitutes the reference treatment for renal and ureteric stones in adults, but its use and development in children have been accompanied by a certain degree of caution and reticence. A large number of paediatric series have been published since 1986, confirming the efficacy and minimally invasive nature of this technique. Modification of the nature of the shock waves and release onto the market of second and third generation apparatuses have simplified the management of urinary stones in children. However, several questions persist concerning the maximum number of impacts, the recommended interval between two sessions and the long-term effects of shock waves on the growing renal parenchyma. The objective of this study was to review the current state of ESWL in children based on a review of the literature, the GEUP report and our own experience. PMID- 11217571 TI - [Intent to treat]. AB - Intent to treat methodology consists of keeping all patients included, in their initial group in the case of randomization, to perform final analysis of a study. This attitude is justified methodologically, as it preserves the validity of the statistical rationale, and clinically, as it more closely reproduces real prescribing conditions. In the light of a classical example, this review illustrates several clinical situations raising the problem of intent to treat. PMID- 11217572 TI - [Critical review of quality of life scales]. AB - Methods of construction and required metrologic properties of quality of life scales are reviewed while looking for such tools in the field of urinary tract infections. To capture the subjectivity of patients, to reach a simple measure scale, to build a reliable tool, are conflicting aims. Although they appeared several years ago and are broadly spread in all medical fields, including urology, quality of life scales are still in early ages and are not always widely admitted. Quality of life scales can be criticized, but they capture specific data and are very useful in some fields. Today, there are no quality of life scales in the field of urinary infectiology. PMID- 11217573 TI - [Indication and strategy for further biopsies following the diagnosis of prostatic intra-epithelial neoplasia]. AB - Prostatic Intraepithelial Neoplasia (PIN) lesions are characterized by proliferation of the epithelial cells lining prostatic ducts and acini. Only high grade PIN lesions (grades 2 and 3) should be reported on biopsy histology reports. The authors present a review of the literature. The clinical importance of demonstration of isolated PIN lesions on prostatic biopsies is based on the high risk of associated invasive cancer present in the prostatic gland in 22% to 100% of cases, usually adjacent to the zone presenting PIN lesions. This risk increases as the grade of the PIN lesion increases, when there is a clinical (abnormal digital rectal examination) or laboratory suspicion (elevation PSA > 10 ng/ml), or in elderly patients. Identification of a high grade PIN does not require any immediate treatment decision. PSA assays do not need to be repeated. A new series of biopsies is recommended after three months. The optimal strategy for the choice of the new biopsy sites has not been defined. In the case of a first series of sextant biopsies, a new series of biopsies is recommended, combining biopsies directed towards the site of PIN lesions (3 biopsies in the site of PIN lesions, 2 biopsies adjacent to this site) and systematized biopsies of the same side. In the case of a first series of non-systematized biopsies, a new series of systematized biopsies is recommended. PMID- 11217574 TI - [Prostatic biopsies: technical modalities and conditions of the test]. AB - Histological examination of prostate biopsies is necessary for the diagnosis of prostate cancer. The technical modalities and examination conditions of prostate biopsies were evaluated in the light of a review of the literature and the conclusions are presented in the form of standards, options and recommendations. STANDARDS: The standard or modified protocol of 6 sextant biopsies, applied as first-line investigation in all cases of stage T1c or T2 prostate cancer is a standard procedure and remains a reproducible, effective and well tolerated method for diagnosis and staging. Rectal preparation by enema and prophylactic antibiotics before the examination decrease the risk of infectious complications. In its usual modality used for the majority of patients, biopsies are performed as an outpatient procedure, with or without local anaesthesia, with ultrasound guidance via a transrectal approach using an 18 Gauge needle (pink colour code), mounted on an automatic biopsy gun and especially sampling the posterior and lateral zone. The patient must be given written information explaining the risks and management of possible complications following this examination. OPTIONS: Local, regional or general anaesthesia may be necessary in a minority of cases, either in the context of a protocol of extensive systematized biopsies (more than 10 biopsies), or in the case of repeated examination, or when preferred by the patient. Modified extensive protocols (sextant plus posterolateral zones or sextant plus anterior zones) applied to all cases as first-line procedure is a useful option, particularly when: 1) a first series of biopsies was negative 2) PSA is < or = 10 ng/ml and digital rectal examination is normal (sextant plus posterolateral zones) 3) the prostate is larger than 50 cm3 (sextant plus anterior zones). The transperineal approach is less reliable for detection and staging, and is used when the transrectal approach is contraindicated. When curative treatment is not considered (life expectancy < 10 years, patient's choice, stage T3, T4), the number of biopsies can be decreased. Transurethral resection of the prostate is not recommended as first-line procedure for the diagnosis of prostate cancer. RECOMMENDATIONS: Written information given to the patient during the visit prior to biopsy to explain the objectives, practical modalities and risks of prostate biopsies facilitates the patient's cooperation during the examination and increases its tolerance. PMID- 11217575 TI - [The legislator's position regarding research perspectives (concerning xenografts and the development of stem cell banks]. AB - Analysis of the legislation concerning xenotransplantation and constitution of stem cell banks reveals an absence of status common to embryos and animals. They do not have any legal status, they are not assimilated to objects, but benefit from protective measures. Xenotransplantation is regulated by a set of rules, while embryo research is currently prohibited in France, but is regulated in other countries. Bioethical legislation raises difficulties related to the early stage of its development and its perverse effects. The consultation process prior to defining legislation must take into account the international dimension and the necessary progress of scientific research. PMID- 11217576 TI - [Acute intermittent porphyria: a new hypothesis to explain Jean-Jacques Rousseau's urinary disorders]. AB - We present the main diagnosis concerning Rousseau's, with an emphasis on his urologic disorders. PMID- 11217577 TI - [Re: "The TVT seen from the other side" by Philippe Zimmern]. PMID- 11217578 TI - [Re: "The TVT seen form the other side" by Philippe Zimmern]. PMID- 11217579 TI - [Re: "The TVT seen from the other side" by Philippe Zimmern]. PMID- 11217580 TI - A fluid issue. PMID- 11217581 TI - More about waterlines. PMID- 11217582 TI - Licensure. PMID- 11217583 TI - A flawed report on fractures? PMID- 11217584 TI - Mandatory or elective? PMID- 11217585 TI - Composites vs. Amalgams. PMID- 11217586 TI - Can tomatoes fight oral cancer? PMID- 11217587 TI - Are you now treating or have you ever treated indigent patients, either through a government program such as Medicaid or at a reduced our-of-pocket fee? PMID- 11217588 TI - Prevalence of carpal tunnel syndrome and median mononeuropathy among dentists. AB - BACKGROUND: The authors undertook a study to determine the prevalence in dentists of abnormal sensory nerve conduction and/or symptoms of carpal tunnel syndrome, or CTS, the most common nerve entrapment syndrome. METHODS: In a cross-sectional study, dentists (n = 1,079) were screened during the American Dental Association's Annual Health Screening Program in 1997 and 1998 by means of standard electrodiagnostic measures in the dominant hand and a self-reported symptom questionnaire. The authors diagnosed a median mononeuropathy from a 0.5- or 0.8-millisecond, or ms, prolongation of the median sensory-evoked peak latency compared to the ulnar latency. They diagnosed CTS if the subject also had accompanying symptoms of numbness, tingling or pain. RESULTS: Thirteen percent of screened dentists were diagnosed with a median mononeuropathy (using a 0.5-ms prolongation as the criterion), but only 32 percent of these had symptoms consistent with CTS (4.8 percent overall). When the 0.8-ms prolongation was used as the electrodiagnostic criterion, only 2.9 percent (overall) were diagnosed with CTS. People with diabetes, rheumatoid arthritis and obesity were more likely to have a median mononeuropathy. CONCLUSIONS: The prevalence of symptoms consistent with CTS in the dominant hand among dentists was higher than the prevalence in the general population. However, when electrodiagnostic confirmation is added, the prevalence of CTS was nearly the same as that among the general population. CLINICAL IMPLICATIONS: Early recognition of CTS can lead to more effective management. Education regarding ergonomic risk factors can be an effective preventive measure. PMID- 11217589 TI - Heart murmurs: are older male dental patients aware of their existence? AB - BACKGROUND: The American Heart Association recommends that patients with certain abnormal and prosthetic heart valves receive antibiotic prophylaxis before undergoing invasive dental treatment, owing to the risk of bacterial endocarditis, or BE. However, it is not known how many patients are aware that they have such conditions and understand such recommendations. METHODS: The authors conducted a study to determine how many male users of three U.S. Department of Veterans' Affairs ambulatory medical care centers denied having a heart murmur, even though a murmur was noted in their medical record. The authors asked 637 potential subjects a series of questions to identify those who had a heart murmur that might place them at risk of developing BE. The authors then reviewed each subject's medical records for documentation of a heart murmur. RESULTS: Four hundred ninety-seven dentate men (mean age: 61.0 years) denied having a heart murmur. Seventy (14.1 percent) of these men had documentation of a heart murmur in their medical records, and 13 (2.6 percent) had murmurs that were likely to be pathological. The failure to accurately report having a heart murmur and having a potentially pathological heart murmur were positively related to age (P = .001). Failure to accurately report having a heart murmur also was related to lower educational levels. CONCLUSIONS: These results indicate that a substantially larger number of older men than younger men were unaware that they had a heart murmur. Since some of these murmurs necessitate administration of antibiotic prophylaxis before dental procedures, this failure to communicate their correct medical status may put them at risk of developing BE. CLINICAL IMPLICATIONS: Dental health care providers should be aware that patient self report may not be a reliable indicator of cardiac status, particularly in older patients. PMID- 11217590 TI - Articaine hydrochloride: a study of the safety of a new amide local anesthetic. AB - BACKGROUND: Articaine is an amide local anesthetic introduced clinically in Germany in 1976 and subsequently throughout Europe, Canada and, in 2000, the United States. METHODS: The authors report on three identical single-dose, randomized, double-blind, parallel-group, active-controlled multicenter studies that were conducted to compare the safety and efficacy of articaine (4 percent with epinephrine 1:100,000) with that of lidocaine (2 percent with epinephrine 1:100,000). RESULTS: A total of 1,325 subjects participated in these studies, 882 of whom received articaine 4 percent with epinephrine 1:100,000 and 443 of whom received lidocaine 2 percent with epinephrine 1:100,000. The overall incidence of adverse events in the combined studies was 22 percent for the articaine group and 20 percent for the lidocaine group. The most frequently reported adverse events in the articaine group, excluding postprocedural dental pain, were headache (4 percent), facial edema, infection, gingivitis and paresthesia (1 percent each). The incidence of these events was similar to that reported for subjects who received lidocaine. The adverse events most frequently reported as related to articaine use were paresthesia (0.9 percent), hypesthesia (0.7 percent), headache (0.55 percent), infection (0.45 percent), and rash and pain (0.3 percent each). CONCLUSIONS: Articaine is a well-tolerated, safe and effective local anesthetic for use in clinical dentistry. PMID- 11217591 TI - Intralesional corticosteroid injection for treatment of central giant-cell granuloma. AB - BACKGROUND: The central giant cell granuloma, or CGCG, is a benign intraosseous lesion of the jaw. It is found predominantly in children and young adults. It is an asymptomatic lesion, which often becomes evident on routine radiographic examination. Giant cell lesions have been described as both nonaggressive and aggressive in nature, with recurrence noted in cases of aggressive lesions. Central giant cell lesions present as unilocular or multilocular radiolucent defects on radiographs. Multinucleated giant cells within a collagenous stroma are the characteristic histopathologic feature of CGCG. CASE DESCRIPTION: The authors describe a 10-year-old girl with an expansile lesion of the mandible. The panoramic radiograph showed a well-circumscribed mixed radiolucent-radiopaque lesion of the left mandibular body. An incisional biopsy of the lesion was performed to establish a histologic diagnosis. The specimen was submitted for frozen-section examination, and a diagnosis of CGCG was made. Serum calcium, parathyroid hormone and phosphorous levels were normal. The patient was treated successfully with intralesional corticosteroid injections. CLINICAL IMPLICATIONS: Central giant cell lesions have been treated surgically with aggressive curettage. More aggressive and recurrent lesions require resection, which leads to major defects of the jaws. This form of surgical treatment can be particularly disfiguring for a child or young adult. An alternative nonsurgical approach is the intralesional administration of corticosteroids, which have been effective in the treatment of CGCG. If a dentist suspects a patient may have CGCG, he or she should refer the patient to an oral surgeon for follow-up. PMID- 11217592 TI - Implant failures associated with asymptomatic endodontically treated teeth. AB - BACKGROUND: Endosseous root-formed implants occasionally fail to osseointegrate. Causes of failure include infection, overheating of the bone, habitual smoking, systemic disease, transmucosal overloading, excessive surgical trauma and implant placement adjacent to teeth demonstrating periapical pathology. CASE DESCRIPTION: In this article, the authors present another possible cause of implant failure. The cases of four patients who received endosseous root-formed implants are discussed. Each patient demonstrated signs of infection after initial implant placement. The common factor in each failing implant was its placement adjacent to an asymptomatic endodontically treated tooth with no clinical or radiographic evidence of pathology. CLINICAL IMPLICATIONS: These patients demonstrate the importance of evaluating and possibly retreating or extracting adjacent endodontically treated teeth before placing implants. PMID- 11217593 TI - Twenty-four-month clinical evaluation of different posterior composite resin materials. AB - BACKGROUND: In a 24-month clinical trial, the authors compared three brands of light-cured composite resins that were used to restore the posterior teeth of 38 patients. METHODS: A total of 88 Class I and 32 Class II restorations were made using Z100 (3M Dental Products Div.), Clearfil Ray-Posterior (Kuraray Co. Ltd.) and Prisma TPH (Caulk/Dentsply). Quadrant impressions were taken using a polyvinyl siloxane impression material, and stone casts were obtained every six months for indirect evaluations of anatomical form and marginal adaptation. The restorations were evaluated directly by three clinicians using the Ryge criteria. RESULTS: The authors statistically evaluated parameters at each recall period, using a chi 2 test; compared baseline scores with the recall scores, using a McNemar test; and evaluated changes in the parameters, using the Cochran Q test. Color match, cavosurface margin discoloration and secondary caries remained unchanged at the end of the 24-month recall period for all materials (P > or = .05). A total of 11.5 percent of the Z100 restorations and 16.7 percent of the Prisma TPH restorations showed a slight crevice along the margin (P < or = .05). The surface texture was scored as Bravo only for Clearfil Ray-Posterior restorations at the end of the study (P < or = .05). The authors found that the indirect evaluation results were different from the direct evaluations for Z100 and Prisma TPH. CONCLUSIONS: According to these findings, all the materials used are suitable for posterior restorations. The difference between the two evaluation methods can be attributed to the level of sensitivity. CLINICAL IMPLICATIONS: With the improvement in materials, careful case selection and application of the restorative techniques, posterior composites placed under appropriate conditions and monitored routinely can be expected to last 10 years or longer. PMID- 11217594 TI - The digital transformation of oral health care. Teledentistry and electronic commerce. AB - BACKGROUND: Health care is being changed dramatically by the marriage of computers and telecommunications. Implications for hospitals and physicians already have received extensive media attention, but comparatively little has been said about the impact of information technology on dentistry. This article illustrates how the digital transformation will likely affect dentists and their patients. CONCLUSIONS: Based on recent experiences of hospitals and medical practices, dentists can expect to encounter revolutionary changes as a result of the digital transformation. The Internet, the World Wide Web and other developments of the information revolution will redefine patient care, referral relationships, practice management, quality, professional organizations and competition. PRACTICE IMPLICATIONS: To respond proactively to the digital transformation of oral health care, dentists must become familiar with its technologies and concepts. They must learn what new information technology can do for them and their patients and then develop creative applications that promote the profession and their approaches to care. PMID- 11217595 TI - Understanding retirement finances. A challenge everyone faces. PMID- 11217596 TI - Community socioeconomic status and children's dental health. AB - BACKGROUND: Although a substantial decline in dental caries has occurred among U.S. children, not everyone has benefited equally. The first-ever surgeon general's report on oral health in America indicates that the burden of oral diseases is found in poor Americans. This study investigates the relationship between community socioeconomic status, or SES, and dental health of children. METHODS: An oral health survey of 17,256 children, representing 93 percent of children residing in 62 Tennessee communities, was conducted in public elementary schools during the 1996-1997 school year. Portable dental equipment was used for examinations, and data from each examination were entered directly into a laptop computer. The authors performed analyses of covariance to examine the relationship between community SES (low/medium/high) and dental health, controlling for community fluoridation. RESULTS: Community SES was significantly related to caries experience in the primary teeth, the proportion of untreated caries in the primary and permanent teeth, dental treatment needs, dental sealants and incisor trauma. Overall, dental health was significantly worse for low-SES communities than for medium- and high-SES communities. CONCLUSION: The authors conclude that all specific dental indexes used to measure children's dental health in this study, with the exceptions of caries experience in the permanent teeth and sealant presence, were inversely related to the communities' SES. The percentage of children with dental sealants was directly related to the community's SES. PRACTICE IMPLICATIONS: Further improvements in oral health will necessitate that community-based preventive programs and access to quality dental care be made available to children who are identified as being at highest risk of experiencing oral disease. PMID- 11217597 TI - Protecting your patients. Federal case on discharged employee centers on concerns about patient safety. PMID- 11217598 TI - Treatment of the edentulous mandible. PMID- 11217599 TI - An update on radiographic practices: information and recommendations.ADA Council on Scientific Affairs. PMID- 11217600 TI - Purification of kinesin from the brain. PMID- 11217601 TI - Assays for microtubule-destabilizing kinesins. PMID- 11217602 TI - Green fluorescent protein as a tag for molecular motor proteins. PMID- 11217603 TI - In vitro reconstitution of endosome motility along microtubules. PMID- 11217604 TI - Approaches to study interactions between kinesin motors and membranes. PMID- 11217605 TI - Microinjection methods for analyzing the functions of kinesins in early embryos. PMID- 11217606 TI - The use of dominant negative mutants to study the function of mitotic motors in the in vitro spindle assembly assay in Xenopus egg extracts. PMID- 11217607 TI - A dominant negative approach for functional studies of the kinesin II complex. PMID- 11217608 TI - Identification of kinesin-associated proteins. PMID- 11217609 TI - Expression cloning with pan kinesin antibodies. PMID- 11217610 TI - Assaying spatial organization of microtubules by kinesin motors. PMID- 11217611 TI - Crystallization of kinesin. PMID- 11217612 TI - Structural analysis of the microtubule-kinesin complex by cryo-electron microscopy. PMID- 11217613 TI - Expression of kinesin in Escherichia coli. PMID- 11217615 TI - Preparation of recombinant kinesin superfamily proteins using the baculovirus system. PMID- 11217614 TI - Plasmids for expression of chimeric and truncated kinesin proteins. PMID- 11217616 TI - Assays for kinesin microtubule-stimulated ATPase activity. PMID- 11217617 TI - An improved microscope for bead and surface-based motility assays. PMID- 11217618 TI - RT-PCR for the identification of developmentally regulated novel members of the kinesin-like superfamily. PMID- 11217619 TI - Use of photonic force microscopy to study single-motor-molecule mechanics. PMID- 11217620 TI - High group A streptococcal carriage in the Orthodox Jewish community of north Hackney. AB - BACKGROUND: General practitioners and the microbiologist serving north Hackney in north east London formed the impression, that of throat swabs sent to the laboratory, a disproportionate number of those positive for group A streptococcus appeared to come from Orthodox Jewish patients. AIM: To confirm the clinical impression that the pharyngeal carriage of group A streptococci was higher in the Orthodox Jewish population than in other members of the population in the same locality. DESIGN OF STUDY: A general practice questionnaire survey of all patients aged three years or over attending two practices that are about one kilometre apart, over a five-week period. SETTING: Two general practices in north London, one of which had a significant Orthodox Jewish patient list. METHODS: Throat swabs were taken from eligible patients who were invited to participate by completing a questionnaire and having a throat swab taken. RESULTS: Swabs were taken from 1223 people. After correction for age (child or adult) and history of recent sore throat, the Orthodox Jewish community had a significantly higher carriage rate of group A streptococci than the rest of the population (odds ratio = 5.0 [2.1 to 11.9]). The proportion of adults with group A streptococci with and without sore throats was 6.4% and 2.4% respectively in the Orthodox Jewish group and 0.45% and 1% respectively in the 'others' group. The proportion of children with group A streptococci with and without sore throats was 17.4% and 5.9% respectively and 3.4% and 0% respectively in the others. These differences were not explained by the larger family size and domestic overcrowding in the Orthodox Jewish group. CONCLUSIONS: Orthodox Jews in north London have a higher pharyngeal carriage rate of group A streptococci than the neighbouring population. These results may have implications for the diagnosis and treatment of acute sore throat in Orthodox Jewish patients, especially children. PMID- 11217621 TI - Detection of tongue cancer in primary care. AB - BACKGROUND: The incidence of tongue cancer is increasing, and survival has not improved since the majority of patients present at an advanced stage. Patient delay has remained the same over the years and is difficult to influence. Much less is known about the delay in diagnosis caused by physicians and dentists. AIM: To investigate the detection of tongue cancer in primary care in Northern Finland and to examine the consultation prevalence of oral symptoms in primary care in Finland. STUDY: Analysis of data from medical records of tongue cancer patients kept between 1 January 1974 and 31 December 1994 for the general health insurance scheme. SETTING: The two northernmost provinces of Finland (population of 700,000). METHOD: Data were collected on demographic and clinical variables and on the first medical visit on 75 tongue cancer patients. In addition, primary care physicians recorded all patient visits during four weeks in 25 health centres randomly selected throughout Finland in 1996. RESULTS: At the initial visit, the tongue cancer patient was correctly referred for further examinations in 49 (65%) cases. In 12 (16%) of cases the patient was not referred but was scheduled for a follow-up visit, and was neither referred nor followed-up in 14 (19%). When compared with the referred patients the median professional delay was somewhat longer for the unreferred patients but increased dramatically if no follow-up was arranged (0.6 months [range = 0.1-2.4] versus 1.2 [range = 0.3-2.2] versus 5.2 [range = 0.7-18.2], P < 0.001). Compared with the referred patients the adjusted relative hazard of death for the non-referred followed-up patients was 1.4 (95% confidence interval [CI] = 0.31-6.5) and that for the non referred/not followed-up patients 6.3 (95% CI = 1.7-22.9). The high-risk patients included those who sought an early professional evaluation, those who made the appointment for a completely different reason and only mentioned the symptom suggestive of cancer incidentally, those that had a small ulcerative lesion, and blue-collar workers. Oral symptoms were a rare cause of visits (0.55% of all visits) in primary care in Finland. CONCLUSION: Misdiagnosis of tongue cancer at the initial professional evaluation often leads to a fatal delay if the patient is left without any follow-up. PMID- 11217622 TI - Childhood asthma: can computers aid detection in general practice? AB - BACKGROUND: Childhood asthma remains underdiagnosed in general practice. Computers with a patient interface have the potential to screen children for asthma in a time-efficient manner. AIM: To develop a concise, validated self report measure that calculates an 'asthma score' that predicts likelihood of asthma and its severity in childhood. DESIGN OF STUDY: Computerised questionnaire survey in general practitioners' (GPs') waiting rooms, followed by a written questionnaire and either bronchial challenge or skin allergy testing at the regional teaching hospital. SETTING: Children between 18 months and 18 years old accompanied by a parent or guardian in five group practices in Newcastle in New South Wales, Australia. METHOD: The responses from both the computerised questionnaire and the written questionnaire were compared with physician assessment of asthma, based on an existing validated questionnaire and clinical tests. RESULTS: Six items were identified to be independently and significantly associated (at P < 0.05) with the presence of asthma and its severity: parent or self-reported asthma, previous diagnosis, wheeze in the past year, physical activity affected by symptoms, night cough in the past year, and visits to a GP in the past year. From the regression model a linear score was derived that indicates whether a child is likely to have asthma and its likely severity. CONCLUSIONS: The asthma score is a valid indicator of asthma and its severity in children in general practice. PMID- 11217625 TI - Community hospitals for the new millennium. AB - There is a lack of basic information regarding the numbers of and facilities offered by community hospitals. This survey identified 471 community hospitals in the United Kingdom containing 18,579 beds with 20% of general practitioners having admitting rights. The majority of hospitals provide a comprehensive range of rehabilitation services and consultant outpatient clinics. Community hospitals are potentially an important resource in providing intermediate care in the community. PMID- 11217624 TI - The association between daytime attendance and out-of-hours frequent attendance among adult patients in general practice. AB - BACKGROUND: Frequent attenders (FAs) account for a large proportion of daytime consultations in general practice. However, no studies have so far been conducted to establish whether daytime FAs are also out-of-hours FAs. AIM: To analyse the association between daytime attendance and out-of-hours frequent attendance. DESIGN OF STUDY: A registry-based study of individual face-to-face contacts with general practice during daytime and out of hours, based on National Health Insurance files. SETTING: General practices in Aarhus County, Denmark (630,000 inhabitants). METHOD: A total of 416,172 adults, i.e. all adults registered with a general practice during a 12-month period from November 1997 to October 1998 were included. Odds ratios (OR) for frequent attendance out of hours were stratified for age, sex, and frequency of contacts during daytime were calculated. RESULTS: A strong association was observed between daytime level of attendance and out-of-hours level of attendance (OR = 2.9-6.3 among patients with low daytime attendance, OR = 33.7-99.8 among daytime FAs). Daytime FAs accounted for one-third of the daytime contacts, one-third of the out-of-hours contacts, and 42% of out-of-hours FAs. More than half of the daytime FAs did not attend out of hours. Two per cent of the out-of-hours FAs had no contacts during the daytime. CONCLUSION: Frequent attendance in daytime was very strongly associated with frequent attendance out of hours, and daytime FAs accounted for a large proportion of all contacts with general practice. PMID- 11217623 TI - The use of a screening questionnaire to identify children with likely asthma. AB - BACKGROUND: The theory that airway remodeling and possible fixed asthma may result from failure to treat asthma airway inflammation highlights the importance of the early identification of patients with likely asthma. AIM: To identify children with likely asthma whose condition is unknown to the medical services. STUDY: Postal questionnaire survey. SETTING: Children in two general practice populations in 1999. METHOD: Parents completed the postal questionnaire surveys. Two validated scoring systems were used to identify children with 'likely asthma': first, three or more positive responses to five key questions; second, three or more positive responses to the same five questions and one more severe symptom (e.g. exercise-induced wheeze). Questionnaire responses were linked to practice records to determine those with a recorded diagnosis of asthma (ever) or of inhaled medication (past 12 months). RESULTS: Using the first scoring system, 22.5% of children were identified as having likely asthma; more than one-third of these (35.1%) had no corroborative evidence recorded in the practice records. With the second system, 15.5% had likely asthma, a quarter of whom had no corroborative evidence. Depending on the scoring system chosen, between 3.5% and 8% of children in these practices had likely asthma but no corroborative evidence in their records. CONCLUSIONS: Children identified using either of these scoring systems would require full clinical assessment to determine their need for medical intervention. These findings have implications for the allocation of health care resources. PMID- 11217626 TI - Percutaneous endoscopic gastrostomies: attitudes of general practitioners and how management may be improved. AB - Percutaneous endoscopic gastrostomy (PEG) has replaced surgical gastrostomy in patients requiring long-term enteral nutrition. Increasing numbers of patients are being referred for PEG placement. Concern has been raised about patient selection and subsequent follow-up of these patients in the community. We report the views of Northern Ireland GPs to PEGs and how management may be improved. PMID- 11217627 TI - Consultations owing to adverse drug reactions in a single practice. AB - Data was collected over a six-month period on all patients presenting with a suspected adverse drug reaction. Analysis showed that this was a frequent reason for doctor-patient contact and that a large proportion of adverse reactions were owing to a small group of drugs. PMID- 11217628 TI - Treatment of acute otitis media: are children entered into clinical trials representative? AB - This study involved a meta-analysis of randomised control studies of the treatment of acute otitis media and judged the characteristics of these trials on the basis of methods, age groups, interventions, and outcomes. An investigation of the eight trials reported in the meta-analysis of clinical trials revealed that the number of children entered per doctor in all practices was low and that the recruitment rate was probably lower than 44%. Low recruitment rates indicate that the type of children entered into trials may only relate to those with mild to moderate symptoms and signs, which could explain why the results of these trials show that antibiotics are not essential in treating acute otitis media. PMID- 11217630 TI - GP use and views of an inner-city GP unit. PMID- 11217629 TI - A continuous curriculum for general practice? Proposals for undergraduate postgraduate collaboration. AB - The development of a seamless general practice 'spiral' curriculum, in which topics may be revisited at different levels of intensity and complexity during the learning process, has been discussed in the context of undergraduate postgraduate co-operation. Although the lifelong curriculum for all doctors contains a number of core competencies that aim to produce a 'stem' doctor, concerns remain about the effects of excessive reductionism. It is therefore essential that the content and delivery of the spiral curriculum ensure that intellectual interest is nurtured, by containing both taught theory and training in a hospital context. The opportunity for generalists to teach core competencies such that general practice is at the centre of the undergraduate curriculum- emphasising working within primary health care teams in teaching and training practices--is an ideal area for undergraduate-postgraduate co-operation. The use of the directly observed measures of performance would bring the undergraduate approach to assessment closer to that used in postgraduate general practice. However, supporting the tutors' network is crucial in undergraduate departments where much can be gained by joint working with postgraduate colleagues. PMID- 11217631 TI - What are GPs for? PMID- 11217632 TI - School students and the clinical arena. PMID- 11217633 TI - School students and the clinical arena. PMID- 11217634 TI - Little evidence of safe injecting. PMID- 11217635 TI - Birmingham's condom distribution scheme--an opportunity to promote sexual health in a primary setting. PMID- 11217636 TI - Proposed new law on manslaughter: implications for the NHS and doctors. PMID- 11217637 TI - Sexual health promotion--inner-city style. PMID- 11217638 TI - Rediscovering community hospitals. PMID- 11217639 TI - Improving the diagnosis of childhood asthma. PMID- 11217640 TI - Defining the appropriate use of community hospital beds. AB - BACKGROUND: Patients of GPs who have access to community hospitals (CHs) as well as district general hospitals (DGHs) tend to spend on average more days in hospital each year. Increasing attention is being paid to the efficient management of medical admissions; however, there has been no previous prospective study investigating the appropriateness of CH admissions. AIM: To develop a protocol to assess the clinical appropriateness of admission and length of stay of patients in CHs and to simultaneously compare the appropriateness of admissions to all DGHs and CHs in the county. DESIGN OF STUDY: A protocol named Community Hospital Appropriateness Evaluation Protocol (CHAEP) was developed to assess CH admissions through a process of consultation and a series of pilot studies. The appropriateness evaluation protocol (AEP) was also reviewed and used to assess DGH admissions. SETTING: A prospective cohort of 440 DGH admissions from five DGH sites and 440 CH admissions from nine CHs. METHODS: The admissions were assessed and followed for 28 days. If an admission failed to satisfy any of the criteria then the researcher interviewed the clinician to decide whether it was justified to override the protocol and still classify the admission as appropriate. To assess validity, a proportion of these 'clinical overrides' and the researcher's classifications were reviewed retrospectively by a clinical panel. The kappa statistic was used to assess the level of agreement. RESULTS: Applying the CHAEP, 82% of CH admissions satisfied a criterion for admission and a further 3% were given clinical overrides. A lower intensity of care was required for the majority of the remainder while three admissions required DGH care according to AEP criteria. Sixty-eight per cent of bed days satisfied day-of care criteria within CHAEP and only a further 2% were given clinical override. These results were similar to those found with the AEP at the DGHs where 75% of admissions (plus 16% given clinical override) and 55% of days-of-care (plus 20% given clinical override) satisfied the AEP criteria. The review panel generally did not agree with the clinician's use of the clinical override at the CHs. Agreement between research nurse and review panel was better for the AEP and DGH (kappa = 0.9, 95% confidence interval (CI) = 0.7-1.0) than for the CHAEP and CH (kappa = 0.37, 95% CI = 0.1-0.8). CONCLUSIONS: The CHAEP could be used to audit the appropriateness of admission and length of stay in CHs. Other health communities would need to review the CHAEP before it could be applied within their context. PMID- 11217641 TI - [Clinical management and nephrology: a train we have to catch?]. PMID- 11217642 TI - [Molecular physiology of the urinary concentration mechanism, role of renal aquaporins]. PMID- 11217643 TI - [Logistic regression: a versatile tool]. PMID- 11217644 TI - [Malignant arterial hypertension and acute renal failure caused by cocaine use]. PMID- 11217645 TI - [Inheritance and prevalence of hypercalciuria in the children from the island of La Gomera]. AB - The urinary elimination of calcium has been studies in 549 school children from the island of La Gomera (Canary Islands) and in 100 children of a control group from the capital of the Canaries, Santa Cruz de Tenerife. The diet was not manipulated and it was proven that the water that they consumed was of characteristic equal. The 95th centile for the distribution of the calcium/creatinine index was 0.2 in the control group, we calculated the prevalence of hypercalciuria of this group (3.8%) and of the study group (16%). The prevalence was analyzed by areas of the island and it this showed that it was higher (28.4%) in those from isolated communities and therefore, with history of more inbreeding that in those with good communications (10.6%). It was observed that the risk of suffering hypercalciuria among the children that have four grand parents who are natives of the island of La Gomera is 2.85 times higher than in those that don't have any grand-father/mother coming from the island. Hypercalciuria siblings of children with hypercalciuria found in 50%. PMID- 11217646 TI - [Increase of tubular secretion of creatinine by L-arginine: mechanism of practical significance in the assessment of renal function based on creatinine clearance]. AB - BACKGROUND: Tubular secretion of creatinine is increased by meat meals. This increment has been attributed to the formation of new creatinine from creatine contained in the cooked meals. However, no studies are available using amino acid infusions containing no creatine, which allow to further investigate the putative causes of increment in tubular creatinine secretion. METHODS: We performed a prospective, interventional study involving 34 individuals with normal renal function participating in a protocol on arterial hypertension. A continuous infusion of L-arginine (6%, i.v., in four 30 min periods at 50, 100, 200 and 300 ml/h) was administered. Creatinine (CCr) and inulin (CIn) clearances were determined at baseline and during L-arginine infusion. We analyzed the effects of L-arginine on tubular secretion by comparing CCr and CIn and calculated tubular secretion of creatinine (TSCr). RESULTS: L-arginine infusion induced a significant increase in both CCr and CIn. CCr and CIn were respectively 117.9 +/- 22.7 and 107.5 +/- 23, before and 170.3 +/- 23 and 144.2 +/- 47.8 after the infusion of L-arginine (both p < 0.01). This increase was simultaneous with an increment in TSCr from 1.12 +/- 0.4 to 1.43 +/- 0.6 (p < 0.01). CCr correlated significantly with CIn at baseline and at 60 min of infusion (r = 0.365, p = 0.031 and r = 0.368, p = 0.038, respectively), but not at 120 min (r = 0.130, p = 0.412), a time corresponding to the maximum increase in CIn and TSCr. CONCLUSIONS: L-arginine induces a substantial increase of CCr, which exceeds that expected from the increase in glomerular filtration rate measured by CIn and corresponds to an increment in TSCr. This phenomenon adds a new interpretation of the effect of amino acids on tubular handling of creatinine and has practical implications in the evaluation of renal function by means of creatinine clearance. PMID- 11217648 TI - [Is the correlation between adequate dialysis in peritoneal dialysis and nutritional parameters mathematical or biological? Influence of residual renal function and comorbidity]. AB - The relationship between urea Kt/V and nPCR (nPNA) is partly due to a mathematical coupling and greatly depends on the residual renal function (RRF). On the other hand, albumin could be just a comorbidity marker. Our objective in this study was to verify whether dialysis dose in peritoneal dialysis (PD) is biologically related to the nutritional state measured by the mean values of several parameters not mathematically related while analyzing the influence of RRF and comorbidity (C). 101 stable PD patients, 60M and 41F with a mean age of 59.3 +/- 14.3 years, were studied and followed up every six months for a mean time of 35.8 +/- 22.3 months (8-112). The variables studied were initial comorbidity, plasma albumin, normalized protein nitrogen appearance (nPNA), lean body weight % (LBW%) and fat-free mass index (FFMI) derived from creatinine, and RRF. In every study (n = 471) the 24 hours dialysate and urine volumes were collected and the total (T), dialytic (P) and renal (R) urea KT/V and normalized creatinine clearance (CCR) were determined and compared with the nutritional parameters. When starting PD 48 patients (47.5%) had some C and 34 (33.7%) were already anuric. The correlations of nPNA with T-KT/V and T-CCR (n = 101) were r = 0.67 and 0.50 (p < 0.0005) while the correlations of LBW% with T-KT/V and T-CCR were r = 0.36 and 0.40 (p < 0.0005) respectively. The correlations of albumin with T, P and R KT/V and CCR did not reach significance. The nutritional state was better in patients with a higher RRF and albumin showed significant differences when related to morbidity. KT/V and CCR correlations with nutritional variables not mathematically related verify the hypothesis that dialysis dose is biologically associated with the nutritional state. PMID- 11217647 TI - [Diagnostic and clinical course features of lupus membranous glomerulonephritis]. AB - BACKGROUND: Lupus membranous glomerulonephritis (LMG) is sometimes difficult to distinguish from idiopathic membranous glomerulonephritis (IMG) and little is known about its natural history. METHODS: We have performed a retrospective study of 16 patients with LMG, types Va ("pure" LMG) (8 patients) and Vb (mesangial proliferation) (8 patients). Analytical and clinical characteristics were analyzed in each case at the onset of the disease and during follow-up. RESULTS: At the time of diagnosis, 7 patients (43%) did not present any extrarenal manifestations of systemic lupus erythematosus (SLE). Nephrotic syndrome was the most common clinical presentation (81%). 14 patients (87%) showed positive antinuclear antibodies (ANA), but at low titres (< 1/300); anti-DNA antibodies were positive only in 3 cases (18%) and hypocomplementemia was observed in 2 (12%). The most relevant histological findings were the presence of Clq deposits (83%) and subendothelial and mesangial deposits. Treatment consisted of corticosteroids, adding immunosuppression when no response was obtained in 2-3 months. In recent years, an angiotensin-converting enzyme inhibitor (ACEI) was added before immunosuppression. At the end of the study, 6 patients (42%) developed chronic renal insufficiency and 8 (58%) renainea with normal renal function. Actuarial renal survival was 100% at 5 years and 75% at 10 years. The evolution towards a non-nephrotic range proteinuria throughout the follow-up was the only parameter significantly associated with a good prognosis. CONCLUSIONS: LMG can present without extra-renal symptoms of SLE and even with very poor expression of its serological markers. Almost half of the patients (42%) developed chronic renal insufficiency. The evolution towards a non-nephrotic range proteinuria correlated with the maintenance of a normal renal function. PMID- 11217649 TI - [Nutritional status, comorbidity, and inflammation in hemodialysis]. AB - Low y serum albumin and high C-reactive protein (CRP) have been shown to be significant predictors of mortality in hemodialysis (HD) patients. Although hypoalbuminemia has been attributed to malnutrition, it has recently been recognized evidence of inflammation that predicts serum albumin concentration in dialysis patients. AIM: To establish, in our HD patients, the factors associated with malnutrition, hypoalbuminemia and elevated levels of C-reactive protein to determine its influence in the incidence and cause of death during a one year follow-up period. METHODS: A cross sectional study was performed in 64 patients (35 males, 13% diabetics; mean age 64 +/- 12), who had beep on HD for 64 +/- 58 months. We assessed nutritional status by anthropometric and biochemical parameters and estimated protein and calorie intake by diet recall. The dialysis dose was measure by KT/V normalized for actual and ideal body weight (BW). Comorbidity (total and cardiovascular) were measured using a modified M. Charlson index. CRP was used as a marker of inflammation. During a one year follow-up period we determined the incidence and cause of death. RESULTS: According to Bilbrey index only seven patients (11%) were well nourished. The variables associated with malnutrition were civil status (not married) and dialysis dose estimated by KT/V normalized to ideal BW. Serum albumin (mean 4.1 +/- 0.3 g/dl) was associated with creatinine, comorbidity age and infection. 37.5% of the patients had CRP > 1 mg/dl and they had more cardiovascular comorbidity and lower serum albumin, and they used higher doses of erythropoietin (table III). Patients using modified cellulosic membranes had higher levels of CRP. Multivariate analysis showed that high global comorbidity, low serum cholesterol, and high level of CRP and hematocrit predicted death. The principal cause of mortality was infection. CONCLUSIONS: Malnutrition is a common problem in HD patients. Low dialysis dose is associated with malnutrition in some patients. We propose to normalize urea clearances to ideal body weight. Inflammatory activity is frequent in HD, probably as a result of intermittent activation of the acute phase response during the dialysis procedure. Low serum albumin in HD patients is principally associated with infection/inflammation but not with malnutrition. CRP is a sensitive marker of inflammation and an power predictor of mortality in HD patients. PMID- 11217650 TI - [Late hepatitis C virus seroconversion in a patient on hemodialysis]. AB - We present a case of an exceptionally late HCV seroconversion in a hemodialysis patient. The clinical case illustrates the difficulty of appropriately and quickly isolating a HCV infected patient, and it demonstrates the necessity to consider all the dialysis patients as potentially infectious patients. The standard precautions in hemodialysis must be applied routinely to all the patients, because the diagnosis of the HCV infection is very often late, and on some occasions it is difficult to interpret correctly the results of the available diagnostic tests. PMID- 11217651 TI - [Non-convulsive status epilepticus secondary to adjusted cefepime doses in patients with chronic renal failure]. AB - Fever is one of the most frequent causes of hospital admission in patients with end-stage renal disease. Lack of an identified source of infection and/or lack of clinical response to the first empirical antibiotic treatment favour the use of broader spectrum antibiotics. The availability of fourth-generation cephalosporins (e.g. cefepime) and the increasing incidence of bacterial resistances to classical antibiotics has increased their use in the clinical practice. We present two cases of non-convulsive status epilepticus in patients with advanced chronic renal failure who received cefepime at doses corrected for the degree of renal function according to the manufacturer's instrument as. The clinical symptoms included shouthough, processes, disorientation, loss of attention, and the later appearance of myoclonus. In both cases the electroencephalogram (EEG) was compatible with non-convulsive epileptic status. After cefepime withdrawal there was a clinical remission of symptoms and normalization of the EEG. It is concluded that cefepime treatment can induce a non-convulsive epileptic status in patients with advanced chronic renal failure. Pharmacokinetic studies are urgently needed to clearly define the appropriate dose of cefepime in patients with advanced chronic renal failure. PMID- 11217652 TI - [Hematoma of the anterior rectus abdominis muscle as the first manifestation of lymphoproliferative disease after renal transplantation]. AB - Rectus sheath hematoma results from the rupture of rectus muscle vessels by trauma, coagulation disorders or anticoagulant therapy, but it can occur spontaneously too. Its prognosis is good. On the other hand, posttransplant lymphoproliferative disorders (PTLD) are serious and potentially fatal complications in transplant recipients. Patients with PTLD have a mononucleosis like syndrome or develop extranodal masses which involve various organs. We report the case of a renal transplant recipient who develop a rectus sheath hematoma as the first clinical feature of PTLD. PMID- 11217653 TI - [Ferritin and infection in hemodialysis. Evaluation of a treatment protocol with intravenous iron]. PMID- 11217654 TI - [All you wanted to know about nephrology...]. PMID- 11217655 TI - [Errors in bibliographic references of Nefrologia from 1981 to 1995. A quality control]. AB - The accuracy of the reference list is considered an essential factor in determining the quality of a scientific publication, and has been reviewed and published in several medical journals. The rate of citation errors in NEFROLOGIA has not been published before. The aim of this study has been to examine the accuracy of the references citation in the numbers of the journal published for a period of 15 years, from the first issue in 1981 to the last one on 1995. MATERIAL AND METHODS: In this period 68 ordinary issues of the journal were published, with 520 original articles that constituted the data base, 87 articles were selected applying a table of random numbers with 5 references of each article selected to be reviewed with a total of 435. The accuracy of the name of the authors, title of the article, volume, initial and last page and year of publication were evaluated, accordingly with the NEFROLOGIA normative. Citation errors were considered major or minor depending on whether they prevented or not the immediate retrieval of the article listed. RESULTS: Of the 435 citations examined, 433 could be located, being impossible in 2 with the data supplied. In 189 (43.45%) 237 errors were detected, with 13.50% of them being considered major and 86.50% minor, with the greatest percentage of errors occurring in the data about the authors of the articles referenced 96 (40.50%). CONCLUSIONS: The issues of NEFROLOGIA published in this period present a high number of bibliographic reference errors, being the rate similar to other evaluated scientific periodical journals. This fact should be improved, and authors and reviewers should thoroughly check their references in order to avoid these mistakes, as they affect the quality standard of the publication. PMID- 11217656 TI - [The scientific publication and its critical reading. Standards for the publication of a scientific article. The impact factor]. PMID- 11217658 TI - [Arterial hypertension in Cuba. General overview of the past 25 years]. AB - A general overview of hypertension as a major health problem in Cuba in the last 25 years are presented. In the first period, 1974-1990 was created a National Hypertension High Commission by the Minister of Public and the First national program for prevention and Control of Hypertension in Cuba was launched. To define high blood pressure in adults 15 years and older the cut-off point was set at 160/95 mmHg. The prevalence found was 15% in urban areas and 7-8% in rural areas. The second period, 1991-1998 the original National program was re evaluated in 1990 and 1995. The new blood pressure cut-off point was set at 140/90 mmHg. The prevalence increased to 30.6% in urban areas and 15% in rural areas and incidence of 2.5% annual. A total of 862,303 hypertensive patients were registry at the end of 1997 which represents less than 40% of the total number of possible hypertensive patients. A National Campaign was launched in 1998. In 9 months the preliminary reports were: 25% increase in prevalence, registry and follow-up of hypertensive patients 15 years old and older (8.5% to 12.5%); 92.9% of primary care doctors and 89.5% of primary care nurses received training; improvement in public education and social support; improvement in risk factor awareness in general public and improvement of hypotensive drugs availability and splygmomanometers supplies. PMID- 11217657 TI - [Report on dialysis and transplantation of the Spanish Society of Nephrology for 1998]. PMID- 11217659 TI - Tuberculosis in children. PMID- 11217660 TI - The Bulletin in 2001. PMID- 11217661 TI - Cross-sectional study of sexual behaviour and knowledge about HIV among urban, rural, and minority residents in Viet Nam. AB - OBJECTIVE: A cross-sectional survey was conducted in three districts of Quang Ninh province, Viet Nam, to find out what proportion of the people who lived there engaged in behaviour that put them at risk of becoming infected with HIV, and to measure their knowledge about HIV infection and AIDS. METHODS: The survey was conducted in a rural district, Yen Hung; a mountainous district inhabited primarily by ethnic minority groups, Binh Lieu; and an urban district, Ha Long. Participants aged 15-45 years were randomly selected from the general population to be interviewed. FINDINGS: A total of 630 people from 707 households were interviewed; 8% were not home despite repeated visits and 3% refused to participate. The prevalence of premarital intercourse ranged from 9% to 16% among married men and 4% to 7% among married women. Among single men the proportion who had ever had intercourse ranged from 6% to 16%. Fewer than 3% reported having ever had sex with a sex worker. The median number of extramarital sex partners was 1. Knowledge about HIV/AIDS was high in the urban and rural areas but low in the mountainous area. Being male and being 20-29 years old were associated with having multiple sex partners. CONCLUSION: The low prevalence of individuals reporting that they had had intercourse with sex workers and partners other than their spouse may explain the low rates of HIV infection among the heterosexual population; these rates are in contrast to the high rates of HIV infection found among injecting drug users. The association between having extramarital partners and being a younger man suggests that the tendency to have more sexual partners may increase in the future. If this happens, the potential for HIV to be spread through heterosexual sex will increase. PMID- 11217662 TI - Homicide in children and adolescents: a case-control study in Recife, Brazil. AB - OBJECTIVE: The homicide rate for children and adolescents in Recife, Brazil, mostly caused by firearms, is one of the highest that has been reported. The present case-control study was designed to identify factors that were potentially modifiable through preventive interventions. METHODS: Cases were 255 homicide victims under 20 years of age, who had died in 1997 and been identified at the Institute of Forensic Medicine, Police Department, Recife, and whose relatives were interviewed by two community health workers when they claimed the corpse. The 255 controls were neighbours of the cases, paired by age and sex to them, and identified within one week of identification of each case, and whose relatives were interviewed by a third community health worker. FINDINGS: The overall homicide rate in Recife for under-20-year-olds in 1997 was 49 per 100,000; among males aged 15-19 years it was 324 per 100,000. Firearms were responsible for 97% of deaths. After multivariate logistic regression, history of personal police records (odds ratio (OR) = 18.65; 95% confidence interval (CI) = 1.91-182.50), use of illicit drugs (OR = 7.48; 95% CI = 1.86-30.17), tap water at home (OR = 7.30; 95% CI = 1.80-29.59), and maternal age at birth over 26 years (OR = 3.98; 95% CI = 1.79-8.84) were identified as risk factors, while higher education (OR = 0.22; 95% CI = 0.11-0.43), religious practice (OR = 0.25; 95% CI = 0.10-0.65), and presence of the father in the household (OR = 0.28; 95% CI = 0.09-0.81) were protective factors. CONCLUSION: Public health authorities should plan preventive interventions based on the findings of this study and should control the acquisition, possession and carrying of firearms. PMID- 11217663 TI - The use of hospital-based nurses for the surveillance of potential disease outbreaks. AB - OBJECTIVE: To study a novel surveillance system introduced in Mpumalanga Province, a rural area in the north-east of South Africa, in an attempt to address deficiencies in the system of notification for infectious conditions that have the potential for causing outbreaks. METHODS: Hospital-based infection control nurses in all of Mpumalanga's 32 public and private hospitals were trained to recognize, report, and respond to nine clinical syndromes that require immediate action. Sustainability of the system was assured through a schedule of regular training and networking, and by providing feedback to the nurses. The system was evaluated by formal review of hospital records, evidence of the effective containment of a cholera outbreak, and assessment of the speed and appropriateness of responses to other syndromes. FINDINGS: Rapid detection, reporting and response to six imported cholera cases resulted in effective containment, with only 19 proven secondary cholera cases, during the two-year review period. No secondary cases followed detection and prompt response to 14 patients with meningococcal disease. By the end of the first year of implementation, all facilities were providing weekly zero-reports on the nine syndromes before the designated time. Formal hospital record review for cases of acute flaccid paralysis endorsed the value of the system. CONCLUSION: The primary goal of an outbreak surveillance system is to ensure timely recognition of syndromes requiring an immediate response. Infection control nurses in Mpumalanga hospitals have excelled in timely weekly zero-reporting, participation at monthly training and feedback sessions, detection of priority clinical syndromes, and prompt appropriate response. This review provides support for the role of hospital-based nurses as valuable sentinel surveillance agents providing timely data for action. PMID- 11217664 TI - Home care of malaria-infected children of less than 5 years of age in a rural area of the Republic of Guinea. AB - OBJECTIVES: To assess the ability of mothers in a rural area of the Republic of Guinea to identify fever in their children, and to estimate the proportion of children who received antimalarial drugs. METHODS: Children under 5 years of age in 41 villages were selected by a two-step cluster sampling technique. During home visits we examined the children and questioned their mothers about the child's symptoms and treatment. FINDINGS: Of 784 children examined, 23% were febrile and more than half of them also had a positive smear result for Plasmodium. Mothers reported 63% of children with a temperature > or = 37.5 degrees C as sick. Among all children reported as feverish by their mother, 55% had a normal temperature (< 37.5 degrees C). In contrast, a temperature > or = 37.5 degrees C was found in 38% of children identified as sick but afebrile by their mother and in 13% of children considered healthy. Among febrile children, 18% were given chloroquine at home or had consulted at the health centre or a dispensary. CONCLUSION: In areas where malaria is endemic, recognition of fever and its presumptive treatment with antimalarial drugs is an essential part of the strategy of the World Health Organization (WHO) to reduce the morbidity due to this disease. This population study shows that mothers often failed to identify fever in their children and to consult or to provide antimalarial treatment. Without great efforts to improve home care, it is unlikely that the morbidity and mortality due to malaria in young children will be greatly reduced. PMID- 11217665 TI - Maternal and congenital syphilis in Bolivia, 1996: prevalence and risk factors. AB - OBJECTIVES: The present study was carried out in seven maternity hospitals to determine the prevalence of maternal syphilis at the time of delivery and the associated risk factors, to conduct a pilot project of rapid syphilis testing in hospital laboratories, to assure the quality of syphilis testing, and to determine the rate of congenital syphilis in infants born to women with syphilis at the time of delivery--all of which would provide baseline data for a national prevention programme in Bolivia. METHODS: All women delivering either live-born or stillborn infants in the seven participating hospitals in and around La Paz, El Alto, and Cochabamba between June and November 1996 were eligible for enrolment in the study. FINDINGS: A total of 61 out of 1428 mothers (4.3%) of live-born infants and 11 out of 43 mothers (26%) of stillborn infants were found to have syphilis at delivery. Multivariate analysis showed that women with live born infants who had less than secondary-level education, who did not watch television during the week before delivery (this was used as an indicator of socioeconomic status), who had a previous history of syphilis, or who had more than one partner during the pregnancy were at increased risk of syphilis. While 76% of the study population had received prenatal care, only 17% had syphilis testing carried out during the pregnancy; 91% of serum samples that were reactive to rapid plasma reagin (RPR) tests were also reactive to fluorescent treponemal antibody-absorption (FTA-ABS) testing. There was 96% agreement between the results from local hospital laboratories and national reference laboratories in their testing of RPR reactivity of serum samples. Congenital syphilis infection was confirmed by laboratory tests in 15% of 66 infants born to women with positive RPR and FTA-ABS testing. CONCLUSION: These results indicate that a congenital syphilis prevention programme in Bolivia could substantially reduce adverse infant outcomes due to this disease. PMID- 11217666 TI - Comparison of different culture media and storage temperatures for the long-term preservation of Streptococcus pneumoniae in the tropics. AB - OBJECTIVE: The preservation of Streptococcus pneumoniae by standard freezing methods for subsequent tests--such as serotyping and antibiotic susceptibility- is not possible or is difficult in many developing countries because of the high cost of equipment, inadequate equipment maintenance, and irregular power supply. We evaluated alternative low-cost methods, by comparing different culture media and storage temperatures. METHODS: Clinical isolates of five capsular types (1, 5, 7, 19, and 23) of S. pneumoniae were preserved in rabbit blood, sheep blood, skimmed milk, or glycerol-chocolate broth, and stored at -20 degrees C or -70 degrees C. The cultures were also preserved by lyophilization or sand desiccation, followed by storage at room temperature and 4 degrees C. The viability of the preserved cultures was determined by making serial colony counts on day 0 and after 1 week, 4 weeks, 4 months and 16 months. The viability of cultures preserved by sand desiccation and storage at 4 degrees C was also determined every 6 months for up to 68 months. FINDINGS: Irrespective of the media used, cultures maintained at -20 degrees C became nonviable by the fourth month, while those maintained at -70 degrees C were still viable at 16 months. Cultures preserved by lyophilization or sand desiccation lost their viability by the fourth month when maintained at local room temperature (30-42 degrees C), but remained viable when stored at 4 degrees C for up to 68 months. CONCLUSIONS: Our results confirm that freezing at -70 degrees C, or lyophilization and storage at 4 degrees C are the ideal methods for the preservation of S. pneumoniae. In laboratories where lyophilization is not feasible, sand desiccation and storage at 4 degrees C offers an alternative low-cost method for the long-term preservation of S. pneumoniae. PMID- 11217667 TI - Community-based trials of sexually transmitted disease treatment: repercussions for epidemiology and HIV prevention. AB - This paper reviews the scientific basis for trials exploring the relation between sexually transmitted diseases (STDs) and human immunodeficiency virus (HIV) infection in Mwanza in the United Republic of Tanzania and Rakai and Masaka in the Republic of Uganda. The importance of a study's location and explanations for the divergent results of these trials are discussed. The modest effect on STDs seen in the trial of syndromic management in Mwanza, in contrast to the 38% reduction in the incidence of HIV, casts doubt on the underlying hypothesis that treating STDs alone slows the transmission of HIV-1. According to the Piot Fransen model, the trial in Rakai, which offered treatment of STDs to all subjects irrespective of symptoms ("mass" treatment), should have been more effective both in reducing the prevalence of STDs and the incidence of HIV. However, the Rakai trial was stopped because there was no difference in the incidence of HIV between the intervention and control arms. If Mwanza is seen as the trial that needs explaining, another paradigm becomes relevant. In rural East Africa, where all trials have been conducted, networks of concurrent sexual partnerships are a source of infection with both STDs and HIV. Because of their shorter latency periods, STDs may prompt attendance at a clinic before the early signs of HIV-1 infection appear. Part of the management of STDs is to recommend abstinence or the consistent use of condoms until treatment is completed. This recommendation may cover the earliest period of viraemia during primary HIV-1 infection. This paradigm appears to explain the results from Mwanza and Rakai, emphasizing behavioural aspects of syndromic management. PMID- 11217668 TI - STI care: one of many necessary approaches for prevention of HIV infection. PMID- 11217669 TI - More community-based trials of STD control or more appropriate interventions: which is the priority for preventing HIV-1 infection in developing countries? PMID- 11217670 TI - The rationale for recommending fixed-dose combination tablets for treatment of tuberculosis. AB - There is considerable exigency to take all necessary steps to cure tuberculosis cases and prevent further emergence of drug-resistant tuberculosis. The most important of these steps is to ensure that the treatment, particularly of sputum smear-positive cases, is adequate and that patients adhere to their treatment by supervised, direct observation of drug-taking according to the standardized regimens. Use of fixed-dose combinations (FDCs) of tablets against tuberculosis is now being recommended by WHO and the International Union Against Tuberculosis and Lung Disease (IUATLD) as an additional step to ensuring proper treatment. FDCs simplify the prescription of drugs and the management of drug supply, and may also limit the risk of drug-resistant tuberculosis arising as a result of inappropriate drug selection and monotherapy. Only FDCs of proven quality and proven rifampicin bioavailability should be purchased and used. In most situations, blood levels of the drugs are inadequate because of poor drug quality rather than poor absorption. This is true irrespective of the human immunodeficiency virus (HIV) infection status of the tuberculosis patients (other than those with overt acquired immunodeficiency syndrome, with CD4 counts < 200 cells/mm3). Currently, WHO, IUATLD and their partners are developing strategies for ensuring that only quality FDCs are used in tuberculosis programmes. A simplified and effective protocol for assessment of rifampicin bioavailability has been developed, and laboratories are being recruited to form a supranational network for quality assurance of FDCs. Standardization of FDC drug formulations has been proposed, which limits rifampicin-containing preparations to nine (including a four-drug FDC and three paediatric FDCs). PMID- 11217671 TI - Kochi's tuberculosis strategy article is a "classic" by any definition. PMID- 11217672 TI - Comparison of malaria control interventions. PMID- 11217673 TI - AIDS--dramatic surge in ex-Soviet Union, no respite worldwide, new data show. PMID- 11217674 TI - Experimental vaccine protects monkeys against Ebola virus. PMID- 11217675 TI - Pilot study of the use of community volunteers to distribute azithromycin for trachoma control in Ghana. AB - OBJECTIVE: To assess the skills of community health volunteers in diagnosing active trachoma and distributing azithromycin in the Northern Region of Ghana. METHODS: Six community health volunteers from Daboya were trained to diagnose trachoma and to treat the disease using azithromycin. They were also informed of the drug's possible side-effects. Under supervision, each volunteer then examined, and if necessary treated, 15 households. The dose of azithromycin was determined by weight; height was also measured. Tablets were given in preference to suspension when possible. RESULTS: The volunteers' diagnostic sensitivity for active trachoma was 63%; their specificity was 96%. At the household level, their "decision to treat" was correct in 83% of households. In 344 treatment episodes, volunteers planned a dose of azithromycin outside the range 15-30 mg/kg on only seven occasions (2.0% of all planned treatments). The volunteers' drug management skills were good, the response of the community was excellent, and adverse reactions were infrequent. Diagnosis of active trachoma, record-keeping skills, and knowledge of side-effects were found to need greater emphasis in any future education programme. Most people aged four years or older were able to swallow tablets. For those taking tablets, the correlation between the data gathered for height and weight shows that calculating azithromycin doses by height is a valid alternative to calculating it by weight. CONCLUSION: Trained community health volunteers have a potential role in identifying active trachoma and distributing azithromycin. To simplify training and logistics, it may be better to base dosage schedules on height rather than weight for those taking tablets, which included most people aged four years or more in the population studied. PMID- 11217676 TI - [Living donors in kidney transplantation. Renaissance by non-related donors?]. AB - Renal Transplantation is hampered worldwide by the continuing lack of cadaveric organs. The discrepancy between the number of patients on the waiting list and the number of organs available is further compounded by the still unresolved problem of chronic transplant failure. Against this background, the arguments for increasing acceptance of the use of kidneys from living donors, both related and unrelated, are discussed. Initial reports on appreciably improved transplant survival rates of organs from unrelated living donors (85% survival after 3 years [19]) have since been confirmed by more recent studies. Our own results, in part obtained during a prospective study involving 103 patients (53 related, 50 unrelated) done between October 1994 and April 1999, with strict psychological care/evaluation prior to and after transplantation, revealed a four-year transplant survival rate of 98% in both groups. So far, the higher rejection rate of 34% in unrelated, vs. 13.2% in related, donors has not led to any earlier chronic dysfunction of the transplant. The expanded use of living kidney donors is not only ethically justifiable, but also improves the outcome. PMID- 11217677 TI - [Intensified conventional insulin therapy in patients with type 2 diabetes mellitus. Positive long-term effects of insulin lispro on metabolic control and microalbuminuria]. AB - AIMS: It was decided to demonstrate by the present observations to which extent beneficial long-term effects on metabolic control, body weight and microalbuminuria can be attained by applying intensive insulin therapy (IIT) to type 2 diabetic patients, particularly when using insulin lispro. METHODS: In our observational study, clinical data were evaluated during 6, 12 and 36 months after participation in our structured inpatient insulin treatment and teaching programme in 25 patients with conventional insulin therapy (CT), in 10 patients with IIT using human normal insulin and in 15 patients with IIT using insulin lispro who all could be followed for 3 years in our outpatient diabetic clinic. RESULTS: In the CT-treated patients, HbA1c decreased from 10.2 +/- 0.4% to 7.6 +/ 0.2% (average +/- SEM) after 3 years. Body weight increased from 27.8 +/- 0.9 kg/m2 to 28.6 +/- 0.9 kg/m2, insulin dose increased from 29 +/- 3 U/day to 48 +/- 5 U/day (all p < 0.05), urinary albumin concentration was only transiently reduced. In the IIT-treated patients using human normal insulin, HbA1c fell from 10.6 +/- 0.8% to 7.9 +/- 0.5%, body weight increased from 27.8 +/- 1.4 kg/m2 to 29.8 +/- 1.3 kg/m2, urinary albumin concentration was reduced from 26 +/- 10 mg/l to 13 +/- 3 mg/l (all p < 0.05). Insulin dose increased only slightly from 57 +/- 6 U/day to 63 +/- 7 U/day. In the IIT-treated patients using insulin lispro HbA1c fell from 8.4 +/- 0.5% to 6.7 +/- 0.3%, body weight increased from 27.6 +/- 1.0 kg/m2 to 28.7 +/- 1.3 kg/m2, insulin dose from 36 +/- 5 U/day to 50 +/- 7 U/day, urinary albumin concentration was reduced from 23 +/- 4 mg/l to 13 +/- 4 mg/l (all p < 0.05). Blood pressure remained uninfluenced by insulin therapy. CONCLUSION: In our patients, we observed a beneficial long-term effect on metabolic control of IIT-treatment using insulin lispro, which was evident over the complete 3-year observation period, together with an only moderate increase in insulin dose and a clinically acceptable increase in body weight, but a remarkable reduction of microalbuminuria. Thus, clinical outcome was superior to that in patients treated with CT or IIT using human normal insulin. PMID- 11217678 TI - [Dexketoprofen-trometamol and tramadol in acute lumbago]. AB - BACKGROUND, METHOD: The analgesic efficacy and tolerability of dexketoprofen trometamol (DKPT) was compared with tramadolhydrochloride (TRAM) in a multicentre, randomised, double-blind, clinical trial in 192 Patients with acute low back pain. The initial pain at rest and on movement should be at least 50 mm on a 100 mm visual analogue scale. The daily dose during the 7 days' treatment was 50 mg TRAM t.i.d. (n = 95) or 25 mg DKPT t.i.d. (n = 97). The patients were allowed to take additional Paracetamol up to 4 x 500 mg per day as rescue medication. RESULTS: From the 4th day of treatment pain on movement decreased significantly (p = 0.044) in the DKPT-group in comparison with the TRAM-group. The nocturnal pain decreased during the treatments with a difference in therapies of 22.9% in favour of DKPT. Within the DKPT-group the patients required additional Paracetamol more often only during the 1st day of treatment whereas the patients of the TRAM-group required the additional rescue medication mainly during the first 3 days of treatment. This difference was statistically significant (p = 0.011). Under DKPT treatment patients experienced significantly less adverse events (with an at least "possible" causal relationship; p = 0.026). This can be explained by central nervous disturbances that occurred only in the TRAM group. The distribution of gastro-intestinal disorders was identical in both treatment groups. CONCLUSION: With this results DKPT in comparison with TRAM also showed to be a strong analgesic drug with a better risk-benefit relation due to its better tolerability. PMID- 11217679 TI - [Differential diagnosis of pain experience. Chronic pain and depression]. AB - Chronic pain and depressive symptoms often occur together. The relationships between these two conditions are, however, still controversial. On the neurobiological level, features common to both disorders are to be found. Mental coping patterns favor the development of depressive symptomatology in patients suffering from pain, or of pain within the framework of a psychiatric illness. For the diagnostic work-up, the case history, exploration, organic investigations and, where indicated, psychological tests are employed. A well-proven strategy in the areas of diagnosis and therapy is interdisciplinary cooperation involving physicians, psychologists and--within relevant institutions--nursing staff. PMID- 11217680 TI - [Ginkgo special extract EGb 761 in tinnitus therapy. An overview of results of completed clinical trials]. AB - In a systematic search of the literature 19 clinical trials investigating the effects of tinnitus treatment with Ginkgo biloba special extract EGb 761 were identified and evaluated. The results of eight controlled studies on tinnitus due to cerebrovascular insufficiency or labyrinthine disorders of varying genesis for the most part show a statistically significant superiority of treatment with the Ginkgo biloba special extract EGb 761 as compared with placebo or reference drugs applied of periods of one to three months. Open studies, too, some involving large numbers of patients, revealed appreciable improvements under ginkgo treatment. Therapeutic success was not directly correlated with either the genesis or the duration of tinnitus. However, investigations of prognostic factors revealed that short-standing disorders have a better prognosis, so that better results can be expected from early-onset treatment. The tolerability of Ginkgo biloba special extract EGb 761 was excellent, and in this respect the controlled clinical trials revealed little difference between drug-treated and control groups. PMID- 11217681 TI - [Normal and pathological aging of the brain]. AB - The number of people of old age in western countries is growing, leading to an increased prevalence of degenerative brain diseases. These diseases are widely regarded as a limiting factor of quality of life in old age. The possibilities to maintain intellectual performance of the brain even in old age historically met with scepticism and diseases like Alzheimer's or Parkinson's disease were accepted as an inevitable consequence of aging. "The older, the sicker." However, during recent years new concepts were developed: The physiologic aging of the brain is distinct from diseases of the brain occurring during old age and pathogenesis of degenerative brain diseases is increasingly revealed. This results in novel, even neuroprotective, therapy strategies, implying that these diseases cannot only be seen as inevitable and incurable, but also as a target for prevention and symptomatic and causal therapy strategies. PMID- 11217682 TI - [Combined vaccine against tetanus, diphtheria and polio. A randomized controlled study of immunogenicity and tolerance]. AB - BACKGROUND, METHOD: Given the worldwide distribution of infection and the mobility of large parts of the population immunizations against tetanus, diphtheria and polio remain a challenge. This is especially true for adolescents and adults since antibodies tend to wane once immunized children enter adolescence and adulthood. A new combination vaccine against tetanus, diphtheria and polio (Td-IPV) for booster immunizations was subjected to a randomized, controlled and single-blind trial. Non-inferiority had to be demonstrated with regard to efficacy (immunogenicity) and safety in comparison to separate Td and IPV injections. RESULTS: Almost 500 subjects from community practices and occupational/immunization clinics took part. Antibody titres were equivalent for all antigens. Local and systemic reactions were equal or even less marked in the intervention group. CONCLUSION: From a public health perspective the new vaccine can make an important contribution to ensure adequate protection against tetanus, diphtheria and polio in adolescent and adult populations. PMID- 11217684 TI - Bibliography. Current world literature. Neoplasms. PMID- 11217683 TI - [Prescribing of sildenafil by national insurance program physicians. What basic sexual medicine qualification is required?]. AB - The role of sildenafil in the treatment of erectile dysfunction is discussed. Especially in primary care there is a necessity to weigh the individual cost benefit-ratio. Functional analysis of erectile dysfunction, exclusion of psychiatric and organic comorbidity, identification of sexual deviance and couple counseling about the advantages and disadvantages of sildenafil prescription are the core prerequisites of sildenafil application in primary care. The counseling model of PLIS-SIT is proposed as a guideline for counseling process. Current approaches of education for general practitioners are reviewed and the integration in a recently developed training for management of psychiatry and psychosomatic illness in general medical settings is proposed. Finally open questions for research and quality management are discussed. PMID- 11217686 TI - Bibliography. Current world literature. Metabolic disorders and neurotoxicology. PMID- 11217685 TI - Bibliography. Current world literature. Trauma and rehabilitation. PMID- 11217687 TI - [Guidelines of the DGVS. Complementary therapy. German Society of Digestive and Metabolic Diseases]. PMID- 11217688 TI - [A 57-year-old woman with progressive disturbance of gait and mental deterioration]. AB - We report a 57-year-old woman with progressive gait disturbance and mental deterioration. She was well until March 1995, when she was 54 years of the age. At that time she noted a gradual onset of tremor and difficulty using her hand. Similar symptoms appeared in her right hands, and she visited another hospital, where 300 mg of levodopa and 7.5 mg of bromocriptine were prescribed. These medication did not help her symptoms. In the summer of 1996, she became to fall down easily. In September of the same year, she started to repeat the same words many times. She was unable to stop it. She was hospitalized to our service on January 25, 1997. On admission, she was alert but demented moderately; her Hasegawa dementia scale was 15/30. She showed palilallia, logoclonia, and echolalia. She showed constructional apraxia and questionable left-right disorientation. She had marked vertical gaze palsy with preserved oculocephalic response. She had masked face and small voice. Her gait was wide based with small steps. No muscle atrophy or weakness was noted. She showed only mild rigidity in the neck, but no rigidity was noted in the limb. No tremor was noted. She was bradykinetic. Deep tendon reflexes were symmetric and within normal limits. Laboratory findings on admission was unremarkable. MRI showed atrophy of the brain stem as well as cerebral cortical areas, particularly in the fronto temporal region. Her hospital course was complicated with paralytic ileus and septicemia. She developed hypotension and pronounced dead on July 28, 1998. She was discussed in the neurological CPC. The chief discussant arrived at a conclusion that the patient had progressive supranuclear palsy and died of septic shock. All the participants wondered between PSP and CBD, but majority agreed with this diagnosis of the chief discussant. Only one thought that she might have had corticobasal degeneration rather than PSP, because of dementia, cortical atrophy in MRI, and lack of limb rigidity. Postmortem examination revealed cortical and brain stem atrophy. In the premotor cortex, marked astrocytosis and ballooned neurons were seen. Furthermore, astrocytic plaques were seen; this is considered to be pathognomonic for CBD. The substantia nigra showed marked neuronal loss and gliosis, but no neurofibrillary tangles or Lewy bodies were seen. Gliosis was also seen in the globus pallidus and in the medial thalamus. The pathologic diagnosis was corticobasal degeneration. This patient was very interesting case, in that the clinical manifestations appeared to be consistent with PSP, yet pathologic diagnosis was CBD. Lack of limb rigidity may be atypical for advanced PSP. In addition, palilalia appears to be more associated with CBD. PMID- 11217689 TI - Knowledge is not enough. PMID- 11217690 TI - Proposed design modifications to reduce risk of operating rotary field mowers. AB - The primary objective of this project was to reduce risk of injury associated with operating a rotary mower driven by a tractor power take-off (PTO) by developing and evaluating design improvements and determining their economic feasibility. Researchers have concluded that alteration of machinery design has a greater impact on the reduction of accidents than safety training. Implementation of an Operator Presence Sensing System (OPSS) and removal of the PTO are the two injury-reducing, engineering modifications evaluated by this research. Hydraulic power allows this to occur by providing dynamic braking, few moving parts (removal of the PTO), and controllable power. A hydraulic circuit was developed to power the mower and to enable an OPSS. Tractor hydraulics were simulated using a hydraulic training bench. Two mower configurations were tested: 6.55 cm3 rev( 1) (0.4 in.3 rev(-1)) displacement motor with a 0.748 kg blade and 47.5 cm3 rev( 1) (2.9 in.3 rev(-1)) displacement motor with a 9.4 kg blade. A PTO-driven rotary mower was not used to test the circuit due to spatial and safety limitations of the hydraulic training bench. Results from the first mower configuration verified the concepts behind the hydraulic circuit. The second configuration verified the OPSS and indicated the applicability of the circuit to a rotary mower. PMID- 11217691 TI - Dust in pig buildings. AB - It is well documented in the international scientific literature that airborne dust in pig houses can cause serious health problems for humans as well as for animals. Extensive research has been carried out in different countries during the last few decades to improve the scientific understanding of air quality issues related to intensive animal production. Research and review papers were presented at the international symposium on Dust Control in Animal Production Facilities, held in Denmark in 1999. Different techniques have been used in order to reduce dust burdens in pig confinement buildings, but up to date only the procedure of spraying oil or a mixture of oil and water has contributed to reducing the indoor dust concentrations significantly. This article summarizes the current level of understanding of dust issues in intensive animal production buildings, mainly on the basis of papers presented at the above-mentioned symposium. PMID- 11217692 TI - Dust levels and control methods in poultry houses. AB - This article summarizes information from the papers and posters presented at the international symposium on "Dust Control in Animal Production Facilities", held in Aarhus (Denmark) on 30 May-2 June 1999. Dust concentrations in poultry houses vary from 0.02 to 81.33 mg/m3 for inhalable dust and from 0.01 to 6.5 mg/m3 for respirable dust. Houses with caged laying hens showed the lowest dust concentrations, i.e., less than 2 mg/m3, while the dust concentrations in the other housing systems, e.g., perchery and aviary systems, were often four to five times higher. Other factors affecting the dust concentrations are animal category, animal activity, bedding materials and season. The most important sources of dust seem to be the animals and their excrements. Further studies on the effects of housing systems on dust sources and their compounds are desired for development of a healthier working environment in poultry production facilities. Adjustment of the relative humidity (RH) of the air in a broiler house to 75% will have an effect on inhalable dust, but not on respirable dust. A slight immediate effect on the respirable dust was observed after fogging with pure water or water with rapeseed oil. In an aviary system, a 50 to 65% reduction of the inhalable dust concentration was found after spraying water with 10% of oil and pure water, respectively. To obtain a higher dust reducing efficiency, improvement of techniques for application of droplets onto dust sources will be desired. PMID- 11217693 TI - Human health effects of dust exposure in animal confinement buildings. AB - Work in swine and poultry units is associated with exposure to significant levels of organic dust and endotoxins with the highest concentrations found in poultry houses, whereas values found in dairy and in cattle farming are much lower. Corresponding to this is an excess of work-related respiratory symptoms in swine farmers. A dose-response relationship exists between symptoms and number of working hours. Longitudinal studies have demonstrated an accelerated decline of lung function in swine farmers large enough to cause clinically significant disease in some farmers. Because of the large number of people needed in swine farming and the long working hours, swine farming has emerged as the major respiratory problem in farming. Experimental studies indicate that exposure has to be lowered substantially to avoid acute effects and longitudinal studies demonstrate that loss of lung function occurs in non-smoking swine farmers without respiratory symptoms and that accelerated decline in lung function occurs below endotoxin concentrations in dust (100 ng/m3) proposed as a safe threshold. PMID- 11217694 TI - Asthma and indoor air: the next epidemic. PMID- 11217695 TI - National Conference on Preventing Hearing Loss in Construction. PMID- 11217696 TI - Workers exposed to class B biosolids during and after field application. National Institute for Occupational Safety and Health. PMID- 11217697 TI - COLCHIC-occupational exposure to chemical agents database: current content and development perspectives. AB - Set up in 1987, COLCHIC is a database for occupational exposure to chemical agents. Eight French regional health insurance fund (Caisse Regionale d'Assurance Maladie-CRAM) interregional laboratories and the French national research and safety institute (Institut National de Recherche et de Securite-INRS) laboratories have stored results and information from chemical agent exposure measurements on this database. More than 10 years later, 400,000 measurement results of exposure to 600 substances are now stored on COLCHIC. Utilization of data from this base is limited by the quality and absence of certain information, so a working group has been formed to develop a new data retrieval system, which takes into account recommendations formulated by the AIHA-ACGIH and European working groups. Utilization of this new coding system should allow improved description of workplace exposure conditions in the near future. This data retrieval system is currently being validated and should be used by the laboratories concerned during the course of 2001. PMID- 11217698 TI - Recording of data of individual measurements of occupational exposure: guideline of the Dutch Society of Occupational Hygiene (October 1999). AB - Following the recommendations of the European Working Group on Exposure Databases, a Working Group (on Storage of Data of Measurements of Occupational Exposure) of the Dutch Occupational Hygiene Society has developed a Guideline which was presented at the International Symposium on Occupational Exposure Databases and Their Application for the Next Millennium, November 1-3, 1999, London. To establish the present situation, a small-scale telephone survey of monitoring practices and storage of data was done within the Society. The results of the telephone survey and the draft guidance document were discussed with the occupational hygienists and other stakeholders (e.g., authorities, industry, labor unions, and occupational physicians) in a society meeting. This meeting was used to gather ideas on the need and support for a guidance document and to get input for improving the draft guidance document and for implementation of the Guideline. After this meeting, the Guideline was further developed and published by the Dutch Occupational Hygiene Society. The Guideline concentrates on the data elements required when storing exposure data. The data elements presented are the minimum and should be stored minimally to ensure proper interpretation of results at present and in the future and definitions of the items used are given. The Guideline does not prescribe how the data should be stored, or which procedures need to be used to guarantee the quality of the recorded data elements. PMID- 11217699 TI - Development of a National Occupational Exposure Survey and Database associated with NIOSH hazard surveillance initiatives. AB - NIOSH pioneered hazard surveillance in the workplace by designing and conducting the 1972 to 1974 National Occupational Hazard Survey (NOHS), the 1981 to 1983 National Occupational Exposure Survey (NOES), and the 1984 to 1989 National Occupational Health Survey of Mining (NOHSM). The databases developed from these three on-site surveys represent unique resources for associating potential chemical, physical and biological agents with industries and occupational groups. The data have been a primary source of information for NIOSH, regulatory agencies, health professionals, researchers, and labor organizations in establishing priorities for prevention strategies that include medical and engineering interventions, development of occupational standards, and the identification of research needs. Recognizing that the data from these surveys are becoming dated, a multidisciplinary team comprising members from various NIOSH research divisions was established to develop a hazard surveillance strategy for the Institute, including options for a national hazard surveillance survey and database. The proposed new hazard survey builds on lessons learned from the previous surveys, seeks opportunities to incorporate existing data from other sources, expands the scope of industries and hazards, and takes advantage of advances in data gathering, processing and dissemination technology. This article presents current considerations and recommendations for a new hazard survey and database. PMID- 11217700 TI - Development of an exposure database and surveillance system for use by practicing OSH professionals. AB - This report summarizes the development of an occupational exposure database and surveillance system for use by health and safety professionals at Rocky Flats Environmental Technology Site (RFETS), a former nuclear weapons production facility. The site itself is currently in the cleanup stage with work expected to continue into 2006. The system was developed with the intent of helping health and safety personnel not only to manage and analyze exposure monitoring data, but also to identify exposure determinants during the highly variable cleanup work. Utilizing a series of focused meetings with health and safety personnel from two of the major contractors at RFETS, core data elements were established. These data elements were selected based on their utility for analysis and identification of exposure determinants. A task-based coding scheme was employed to better define the highly variable work. The coding scheme consisted of a two tiered hierarchical list with a total of 34 possible combinations of work type and task. The data elements were incorporated into a Microsoft Access database with built-in data entry features to both promote consistency and limit entry choices to enable stratified analyses. In designing the system, emphasis was placed on the ability of end users to perform complex analyses and multiparameter queries to identify trends in their exposure data. A very flexible and user friendly report generator was built into the system. This report generator allowed users to perform multiparameter queries using an intuitive system with very little training. In addition, a number of automated graphical analyses were built into the system, including exposure levels by any combination of building, date, employee, job classification, type of contaminant, work type or task, exposure levels over time, exposure levels relative to the permissible exposure limit (PELS), and distributions of exposure levels. Both of these interfaces, allow the user to "drill down" or gradually narrow query criteria to identify specific exposure determinants. A number of other industrial hygiene processes were automated by the use of this database. Exposure calculations were coded into the system to allow automatic calculation of time-weighted averages and sample volumes. In addition, a table containing all the PELs and other relevant occupational exposure limits was built into the system to allow automatic comparisons with the current standards. Finally, the process of generating reports for employee notification was automated. The implementation of this system demonstrates that an integrated database system can save time for a practicing hygienist as well as provide useful and more importantly, timely information to guide primary prevention efforts. PMID- 11217701 TI - Retrospective collection of exposure data from industry: results from a feasibility study in the United Kingdom. AB - In the United Kingdom the Health and Safety Executive for some years has stored chemical exposure data in their National Exposure Database. However, it has been difficult to persuade industry and other organizations to contribute to this resource. The aim of this project was to devise a cost-effective method of obtaining occupational exposure data on chemicals from U.K. industry and other sources. Five strategies were used to identify data for three different substances: toluene, acrylonitrile, and ethylene oxide. In total, 810 organizations were contacted and over 45 percent responded. However, only 40 had relevant exposure data. Almost equal numbers of acceptable measurements were identified for toluene and acrylonitrile (2,770 and 2,000 respectively) with lesser ethylene oxide data (800). These measurements were drawn from a wide range of industries and are probably representative of measurements made by U.K. industry, although most of the data were from companies employing more than 100 people. During the second phase of the project, more than 3,000 measurements and associated contextual information were collected (499 for toluene, 1,516 for acrylonitrile, and 17 for ethylene oxide, with a further 1,004 measurements for 1 of 27 substances collected simultaneously with one of the above). The costs of identifying and collecting exposure data ranged from l7 to l380 per valid measurement, depending on the source of the data. We suggest that, rather than trying to retrospectively collect data, it is likely to be more cost-effective to enlist a number of occupational hygiene consults and industrial organizations to prospectively provide anonymized exposure measurements for inclusion in the Health and Safety Executives National Exposure Database. PMID- 11217703 TI - Finnish occupational exposure databases. PMID- 11217702 TI - A task exposure database for use in the alumina and primary aluminium industry. AB - A task exposure database (TED) was developed to facilitate data collation for construction of a task exposure matrix (TEM) for Healthwise, a series of studies on cancer and respiratory morbidity in the alumina and primary aluminium industry. Following the construction of job classifications for the eight study sites, the site hygienists identified all historical air monitoring time-weighted average (TWA) data, from their respective sites. The earliest data were sampled in the late 1970s, and over 17,000 personal samples were recorded over the eight sites over a twenty-year period. TED, a Microsoft Access database, was developed for use by site occupational hygienists to collate these exposure data across the mines, refineries and smelters. All data conforming to strict criteria for use were recorded using TED and provided to the study group. Following the individual data point entry, a calculator program in TED systematically calculated the geometric means, arithmetic means, and maximum and minimum results at the task level. Other features of TED included fields for flagging "significant changes" and "stepwise changes" in exposure. TED established a standardised means of data collation that later formed the basis for the construction of a TEM for the study. A TEM is similar to a job exposure matrix (JEM) except that the basic unit of categorization is at the task level instead of at the job level. Both a TEM and JEM have been constructed independently for Healthwise. The possible reduction of exposure misclassification and improvement in validity of exposure characterization with the use of the TEM, is currently under investigation. The Healthwise TEM consists of annual TWA and peak data results for each site for various airborne contaminants, including fluorides, coal tar pitch volatiles, sulfur dioxide, inspirable dust, alumina dust, bauxite dust, and oil mist. Construction of the TEM for the Healthwise study was completed in late 1998 and consists of over 33,700 TWA years of task exposure data. PMID- 11217704 TI - MEGA-database: one million data since 1972. AB - MEGA is the chemical workplace exposure database of the Institute for Occupational Safety (BIA) of the German Berufsgenossenschaften (BG) (statutory accident institutions for insurance and prevention). On the legal basis of the social insurance law the inspectorates of the BGs conduct workplace measurements of chemical and biological agents. The BGs have cooperated with BIA within the Berufsgenossenschaftliches Messsystem Gefahrstoffe--BGMG since 1972: measurements are done by the BGs, analyses and data processing are the tasks of BIA. In 1999 31,000 measurements with 68,000 analyses were taken in 4,000 enterprises. All data are stored in the MEGA-database with up to 150 pieces of information (describing type of workplace, working conditions, measured substances, sampling strategy, sampling duration, sampling and analytical method etc.), for each result. MEGA contains today about 1,000,000 measurements of more than 400 substances starting in 1972. MEGA is used by BIA and the BGs for the following purposes: prevention (e.g., identification of hazards, efficiency of exposure reducing measures, determination of technical criteria for exposure limit values), epidemiological questions, and investigations of occupational diseases. In the framework of the measuring and inspection activities and tasks of the inspectorates of the BGs the locations for measurements are not randomly selected, but are based on criteria such as supposed critical exposure situations or testing the efficiency of exposure reducing measures. Nevertheless, a statistical appraisal of the data is possible for different purposes considering the specific determinants of the results, as, for example, classification of enterprises (sectors), workplaces (activities, tasks), used materials, and products. The MEGA-database will be further developed into a multifactorial exposure database with additional data on biological exposure to bacteria and funghi, but also noise and other data. PMID- 11217705 TI - Development and initial experience with the new "exposure database of the federal states". AB - The Workgroup of the State Measuring Authorities for Chemical Occupational Safety (ALMA) was established in 1987 by the State Committee for Occupational Safety and Safety Technology (LASI) for the purpose of exchanging experiences between the measuring institutes and authorities of the federal states supporting the commercial regulation authorities in the field of dangerous materials. A workgroup was assigned by ALMA in 1995 to determine the theoretical and practical basis for the establishment of an exposure database commonly available to the federal states. In the first stage, the theoretical data structure of the planned database was defined. The purpose of this was to ensure the exchange of exposure data between the federal states in the future and to allow common evaluation of the data. In the second stage, the practical benefits of the database were determined in a trial run. This database makes possible and simplifies the documentation of both the exposure measurements of the state measuring authorities and also those of external (private) measuring bodies. PMID- 11217706 TI - Dermal exposure: how to get information. AB - Risk assessment of chemical substances at the workplace requires information about intrinsic hazards and workers' exposure. At many workplaces health risks from both inhalative and dermal exposure to hazardous substances may occur. Exposure assessment therefore must include both modes of exposure. Very often, qualitative and quantitative information about dermal exposure is lacking. Measurement methods are of questionable quality when applied to monitoring dermal exposure at workplaces and the results are difficult to interpret. A questionnaire was designed for the description of dermal exposure situations taking into account the different factors influencing dermal exposure. In conjunction with an air monitoring survey in German car repair shops the questionnaire was applied by a hygienist. The hands of car mechanics are the most exposed parts of their bodies. The typical duration of tasks (and dermal exposure) was from either 5-10 minutes or up to about 1 hour. This corresponds to typical jobs in car repair shops like inspection and repair, respectively. In some cases other parts of the body are also exposed, for example, the face and forearms. Parts of the body may be covered by wetted or greasy clothes. Only in a few cases do mechanics clean their hands immediately after finishing a task. Normally, hands are cleaned at the end of a shift. The questionnaire was further developed for general application making use of multiple choice entries together with an explanatory manual. The questionnaire is still under development to be applied for a qualitative survey of dermal exposure as part of the European project RISKOFDERM. PMID- 11217707 TI - Lessons learned while compiling a quantitative exposure database from the published literature. AB - The published literature was reviewed and then a quantitative hydrocarbon solvent exposure database was compiled. The data was then analyzed to determine trends in documented worker exposures to hydrocarbon solvents. It was found that an all too common limitation of the published literature was the incomplete reporting of results by the authors. PMID- 11217708 TI - Exposure information in European industry: implications for future occupational research. AB - A survey has been carried out among European industry to investigate the collection and retention of records which might be used for epidemiological research. Exposure information results are reported. Approximately 1,000 questionnaires focusing on exposure information were sent to seven countries, with a 42 percent response rate. Eighty-two percent of companies reported that exposure measurements were taken to comply with legal requirements. Measurements were most often made for noise (84%), with 48% of companies measuring chemicals, 48 percent particulates but only 10 percent vibration. Measurements were most often taken for specific locations (73%), rather than for particular jobs (54%) or individual workers (50%). Eighty percent recorded location, sampling date, agents measured, and units of measurement, with about 70 percent recording job being sampled, sampling method, and duration and plant process, but less than 60 percent recording environmental conditions or worker details. Overall, only 10 percent of companies kept their exposure information forever, and 71 percent kept it for 10 years or less. Legislative requirements were most often cited as the reason for retention of records. The variation in the quantity and quality of measurements and the early destruction of records poses considerable problems for European research. Inaccuracy and misclassification of exposure limits the ability to establish causal relationships between effect and disease. Records should uniquely identify an individual worker and facilitate linkage to exposure and health effects information. Their format should be accessible, linkable, and secure. Data should be kept by an identifiable organization and there should be a secure chain of custody if a company goes out of business. Unless industry can be motivated to follow these guidelines the future of research into occupational causes of ill health, and in particular, the evaluation of exposure, will be limited. PMID- 11217709 TI - Do EASE scenarios fit workplace reality? A validation study of the EASE model. Estimation and Assessment of Substance Exposure. AB - Within the framework of European risk assessment of new and existing substances, the EASE model (Estimation and Assessment of Substance Exposure) is often applied to assess inhalative exposure at workplaces. To contribute to the validation of this model, single EASE scenarios were compared with independent measurement data on inhalative exposure to vapors and dusts. For this purpose, workplace measurements obtained in the areas of production, textile printing and coating, screen printing and offset printing, the rubber industry, and the plastics processing industry as well as flame spraying were used. A good correspondence between model estimates and measurement data was found in the case of exposure to vapors for the production of chemical substances in closed systems (EASE scenario: closed system without breaching) and for procedural control works at mainly automated printing workplaces (EASE scenarios: non dispersive use, segregation, low/medium volatility). For the handling of powdery substances measurement results obtained during weighing and filling works, in part semiautomatic, were compared with the EASE estimates for the scenario: dry manipulation, with/without local exhaust ventilation. Good correspondence was estimated if approx. 1 t to 200 t powdery substances were handled per shift. For the EASE scenarios "direct handling with natural ventilation/with local exhaust ventilation," high discrepancies exist between model prediction and measurement results obtained during manual screen printing or the preparation of printing inks. PMID- 11217710 TI - Use of rank-order analysis of ordinal exposure data: application to vinyl chloride exposure. AB - The University of Louisville currently maintains a database of work histories and exposure rankings for chemicals used in the production of polyvinyl chloride from the plant where the original angiosarcoma cases were identified. A 6-point ranking scale was used to characterize worker exposure to vinyl chloride by year, building, and job. Since this is ordinal data, non-parametric statistics have been used to evaluate exposure factors in case-control studies. Rank order analysis of vinyl chloride exposure and angiosarcoma shows a strong statistical association. In contrast, the method shows no association between vinyl chloride exposure and brain cancer. Exposure ranking is a reasonable alternative to estimation of actual dose. Rank order analysis allows for a rapid assessment of exposure-disease associations for case control studies. PMID- 11217711 TI - Integrating workplace exposure databases for occupational medicine services and epidemiologic studies at a former nuclear weapons facility. AB - We outline methods for integrating epidemiologic and industrial hygiene data systems for the purpose of exposure estimation, exposure surveillance, worker notification, and occupational medicine practice. We present examples of these methods from our work at the Rocky Flats Plant--a former nuclear weapons facility that fabricated plutonium triggers for nuclear weapons and is now being decontaminated and decommissioned. The weapons production processes exposed workers to plutonium, gamma photons, neutrons, beryllium, asbestos, and several hazardous chemical agents, including chlorinated hydrocarbons and heavy metals. We developed a job exposure matrix (JEM) for estimating exposures to 10 chemical agents in 20 buildings for 120 different job categories over a production history spanning 34 years. With the JEM, we estimated lifetime chemical exposures for about 12,000 of the 16,000 former production workers. We show how the JEM database is used to estimate cumulative exposures over different time periods for epidemiological studies and to provide notification and determine eligibility for a medical screening program developed for former workers. We designed an industrial hygiene data system for maintaining exposure data for current cleanup workers. We describe how this system can be used for exposure surveillance and linked with the JEM and databases on radiation doses to develop lifetime exposure histories and to determine appropriate medical monitoring tests for current cleanup workers. We also present time-line-based graphical methods for reviewing and correcting exposure estimates and reporting them to individual workers. PMID- 11217712 TI - Application of statistical models for secondary data usage of the US Navy's Occupational Exposure Database (NOED). AB - Many organizations around the world have collected data related to individual worker exposures that are used to determine compliance with workplace standards. These data are often warehoused and thereafter rarely used as an information resource. Using appropriate groupings and analysis of OSHA data, Gomez showed that such stored data can provide additional insight on factors affecting occupational exposures. Using data from the Occupational Exposure Database of the United States Navy, the usefulness of statistical models for defining probabilities of exposure above permissible limits for observed work conditions is examined. Analyses have highlighted worker Similar Exposure Groups (SEGs) with potential for overexposure to asbestos and lead. In terms of grouping data, Rappaport et al. defined the Within-Between Lognormal Model, a scale-independent measure for quantifying between-worker variability within a selected worker group: (B)R.95 = exp[3.92s(sB)], representing the ratio of arithmetic mean exposures received by workers in the 97.5th and 2.5th percentiles. To help search for groups, the Proportional Odds Model, a generalization of the logistic model to ordinal data, can predict probabilities for group exposure above the Occupational Exposure Limit (OEL), or the Action Level (AL), which is one-half of the OEL. Worker SEGs have been identified for asbestos workers removing friable asbestos ((B)R.95 = 11.0) and nonfriable asbestos ((B)R.95 = 6.5); metal cleaning workers sandingspecialized equipment ((B)R.95 = 11.3), and workers at target shooting ranges cleaning up lead debris ((B)R.95 = 10). Estimated probabilities for the categories OEL support current understanding of work processes examined. Differences in probability noted between tasks and levels of ventilation validate this method for evaluating other available workplace exposure determinants, and for predicting probability of membership in categories that may help further define worker exposure groups, and determinants of excessive exposures. Thus, analyses of retrospective exposure data can help identify work site and work practice factors for efficient targeting of remediation resources. PMID- 11217713 TI - Assessing reasonable worst-case full-shift exposure levels from data of variable quality. AB - Exposure assessors involved in regulatory risk assessments often need to estimate a reasonable worst-case full-shift exposure level from very limited exposure information. Full-shift exposure data of very high quality are rare. A full-shift value can also be calculated from (short term) task-based values, either derived from measured data or from models. The most simple option is to use the task based exposure levels as the full-shift value. A second option is to calculate a time-weighted average (TWA), using (reasonable worst case) estimates of the duration and the exposure level of the relevant tasks. The third option is to use a Monte Carlo analysis with estimated input distributions for exposure level and duration of exposure. If an estimated distribution of respiratory volume is also included, this leads to a distribution of inhaled amounts. The 90th percentile of such a distribution is generally substantially lower than the fixed point estimates calculated using high end values for each parameter. This technique can thus prevent unnecessary conservative estimates in risk assessment. The output distribution can also be used as valuable input to the risk management process, because it provides information on probabilities of exposure levels, that can influence the cost-benefit analysis of the risk management process. Finally, the sensitivity analysis of Monte Carlo simulation can give guidance for further studies to increase the accuracy of the exposure assessment. PMID- 11217715 TI - What does "low exposure" mean? Exposure considerations in the testing of notified new substances. AB - In the notification procedure for new substances, the need to conduct further toxicity tests may arise if the outcome of a qualitative or quantitative risk assessment indicates relevant risks. Sometimes a quantitative assessment is not possible (e.g., if a no observed adverse effect level [NOAEL] is not available). A different approach is required for such substances. An approach based on the correlation of the classification of the substance (the possible outcome of testing) with the assumed tolerable exposure levels is presented here. It relates to the hazard band model developed by the Health and Safety Executive (HSE) of the United Kingdom. To aid decision-making, the assumed tolerable exposure level is compared with the estimated workplace exposure level by means of calculating the quotient of these two figures. The quotient is called the assumed margin of safety (AMOS). A quotient higher than 1 means that testing may be deferred. The approach is described for a powdery substance used as a pigment in the coloration of plastics and rubber. Depending on the exposure situation, the need for further testing to determine the repeated dose toxicity of the substance is discussed. PMID- 11217714 TI - Harmonization of future needs for dermal exposure assessment and modeling: a workshop report. AB - Dermal exposure assessment and modeling is still in early phases of development. This article presents the results of a workshop organized to harmonize the future needs in this field. Methods for dermal exposure assessment either assess the mass of contaminant that is transferred to the skin, or the transfer of contaminant through the skin. Models for dermal exposure are either knowledge based or deterministic. Any method or model should be transparent, validated, and open to further development. Some (partly) validated and standardized methods are available for measuring or modeling permeation of the skin or of personal protective equipment (PPE). Further validation and standardization is necessary. More research is needed on permeation of dusts and aerosols and more realistic tests should be developed and used for PPE. Several methods have been developed to measure contamination of surfaces or skin, but they are not validated or standardized. A number of non-validated models exist to assess dermal exposure. A clear need exists for more studies of dermal exposure, regarding measurement methods, models and actual exposure levels. A running four-year European study will greatly expand the knowledge in this field. Simple tools to assess and control the risks of dermal exposure in small and medium sized enterprises are also needed. Increasing the general knowledge of practitioners (e.g., safety professionals, occupational hygienists and physicians) in the field of dermal exposure is a first requirement. Available data, for example, on the permeation of PPE, should be made more readily available, using modern information technology. When information on dermal exposure is gathered and stored, the core information needs are partly the same as those for inhalation exposure. Some elements of process and activity, substance and product or worker, specific for dermal exposure, have been suggested by the workshop. PMID- 11217716 TI - The need for empirically derived permeation data for personal protective equipment: the death of Dr. Karen E. Wetterhahn. AB - Personal protective equipment (PPE) is an essential component in any occupational health and safety program. The appropriate selection and use of PPE can help prevent or limit exposure to hazardous materials. The inappropriate selection or use of PPE can lead to unnecessary exposure or --with extremely hazardous materials--serious harm including death. In 1997, Dr. Karen E. Wetterhahn died from mercury poisoning resulting from a single exposure to dimethylmercury almost a year before. Her death raised numerous questions as to how this tragedy occurred and what could be done to protect against a chemical as dangerous as dimethylmercury. This article provides a brief review of the case and discusses the glove permeation testing done during the course of the accident investigation. Using this case as an example, the author argues that all recommendations for PPE be based on empirical testing using accepted methods and that this information be readily available. PMID- 11217717 TI - Determinants of inhalable dust exposure in the European carbon black manufacturing industry. AB - A large study to investigate the respiratory health effects of occupational exposure to carbon black in the European carbon black manufacturing industry commenced in 1987. During the study, a large amount of personal occupational exposure data was collected. This article describes the empirical models used to study the determinants of inhalable dust exposure, using data from 16 factories collected in the third and last cross-sectional phase of this study. Information on activities during the measurements was collected using short job category specific questionnaires. In addition, questionnaires were completed by factory representatives on the implementation of control measures and changes in production process since the first cross-sectional phase. Mixed effects analyses of variance models were used to identify determinants of exposure, while taking into account the within- and between-worker (random) variance components. The results of these models show that, for any job category, factory is a strong predictor of exposure in this industry. These differences could not be explained entirely by factors such as age of the factory or the control measures implemented since the first phase of the study. Surprisingly, implementation of local exhaust ventilation systems had an effect that was counterintuitive; for example, in warehouses where local exhaust ventilation systems had been implemented, higher dust exposure levels were found compared to those where such control measures had not been installed since the first cross-sectional survey. Season appeared to have some effect on exposure for some job titles, with generally relatively low exposures being found in the summer. Finally, a number of activities were identified that caused higher levels of dust exposure, most notably "changing of filters" and "clean-up of carbon black spills." PMID- 11217718 TI - EUROPOEM, a predictive occupational exposure database for registration purposes of pesticides. AB - For registration of agricultural pesticides, the risks for humans, animals, and the environment must be determined. The risk assessment is based on an appraisal of the levels of exposure and the hazards of the active substance(s) in the plant protection product, that is, the agricultural pesticide. Funded by the European Commission (AIR3 CT93-1370), the EUROPOEM database has been developed by a group of experts, representing governments, industry, and academia. The currently available exposure database reflects exposure to operators (mixer/loaders and applicators). The EUROPOEM approach is based on a harmonized protocol for conduct of field studies of operator exposure (presently published as an Organization for Economic Cooperation and Development [OECD] Guidance Document) and a tiered approach to exposure and risk assessment. The database is constructed from exposure data obtained in representative field studies. These field studies are considered according to criteria reflecting the quality of documentation, study design, adequate methodology, number of replicates, and QA/QC elements, for use of the inhalation and dermal exposure data. The resulting exposure data were combined according to comparable use scenarios. From the resulting databases typical surrogate potential exposure values have been obtained, which are determined by their use for either acute or chronic health effects, and the size of the database. For large databases (over 50-100 data points), from many different field studies (10 or more), the 75th percentile is taken if the exposure is considered leading to chronic effects. For smaller databases, a more conservative 90th percentile is taken as surrogate value, or none at all for very small databases (15-20 or less data points from 3 or less different field studies). The choice for the 75th percentile is based on the assumed or observed lognormal distribution of the exposure data, as being the most relevant typical value for long-term effects, since the 75th percentile of log-normal distributions is nominally very similar to a calculated arithmetic mean (AM). The AM, as such however, is irrelevant for log-normal distributions. PMID- 11217719 TI - Misinterpretation and misuse of exposure limits. AB - Users of occupational exposure limits (OELs) often fail to distinguish between the complementary processes of risk assessment and exposure (risk) management. The former refers to those activities that lead to the selection of a reasonably protective exposure limit and often includes an analysis of exposure databases and an evaluation of group-based risk. The latter focuses on individual risk, and refers to those actions required of employers to ensure that each employee is unlikely to incur harm to health. This presentation focuses on how this failure to distinguish leads to misinterpretation and misuse of OELs. A typical OEL definition consists of at least three components: a concentration, an averaging time, and a target (usually the individual worker). OELs are occasionally improperly applied, resulting in a reduction of the expected level of protection. For example, sampling strategies proposed by the American Industrial Hygiene Association (AIHA) and Comite Europeen de Normalisation (CEN) permit workers to be aggregated into exposure groups. Under certain circumstances this practice can leave some workers unevaluated and unprotected. Protection is also reduced when the averaging time is extended from a single shift to multiple shifts. Frequently, OELs are misinterpreted as upper limits to exposures averaged over weeks, months, or even years, rather than a single shift. Much of this confusion can be traced to the desire of some to reconcile research (epidemiology) sampling strategies with compliance sampling strategies. But the two have fundamentally different goals and objectives. Others are simply attracted to alternative OEL interpretations that permit frequent overexposures (i.e., measurements that exceed the OEL), thus making compliance easier. Given the current limitations of industrial hygiene and occupational epidemiology, and the general unwillingness of employers to routinely collect exposure data, OELs should continue to be defined as upper limits for single shift exposures. The current OEL model, which permits the use of proximate risk management goals to realize long-range objectives, should be retained. There are, however, valid reasons for augmenting this model to include criteria for evaluating compliance with long-range objectives. The augmented OEL model would be applicable to future new and revised OELs. The author suggests that OEL setting organizations consider harmonizing definitions and statistical interpretations for both existing and new OELs, thus minimizing future misinterpretation and misuse. PMID- 11217720 TI - A practical approach to exposure assessment programs in the private sector: a partial validation study of a qualitative chemical exposure assessment model. AB - Utilizing a computer-based exposure assessment program, a United States-based chemical company was able to predict which chemicals and tasks presented the greatest probability of exposure in the workplace. The data generated by the model also enabled the company to prioritize these tasks for quantitative exposure monitoring. The assessment program addressed potential chemical exposure to workers in a cost-effective way. This assessment program reduced a facility's cost of complying with the Occupational Safety and Health Administration (OSHA) standard by about 90 percent. Overall, the program reduced the company's cost by about $700,000 when compared to traditional methods used for achieving compliance with these regulations. In addition, by utilizing a computer-based approach, a facility did streamline its chemical exposure assessment process. A comparative evaluation study was conducted in conjunction with a graduate research project. The purpose of the study was to compare the company's qualitative exposure assessment model with several other exposure assessment models. The project compared hazard rankings calculated from three exposure assessment models with actual exposure data for three work scenarios. Overall, the models appeared to be predictive of measured exposures. Therefore, they can be useful tools to help make decisions on which exposures have the highest potential to cause occupational illness to employees and therefore require additional monitoring and follow-up. PMID- 11217721 TI - Time trends in exposure measurements from OSHA compliance inspections of the pulp and paper industry. AB - Time trends in employee exposures to the air contaminants measured by the Occupational Safety and Health Administration (OSHA) during compliance inspections of pulp and paper manufacturing facilities conducted between 1979 and 1997 were evaluated based on the measurement results stored in the OSHA Integrated Management Information System (IMIS) database. The IMIS database is among the largest sources of occupational exposure measurements available for occupational health research in the United States. The IMIS database contains the results of 3,568 personal time-weighted average (TWA) measurements for 171 air contaminants made at 524 establishments in Standard Industrial Classification (SIC) 26. An analysis of these measurements revealed an overall decrease in the total number of measurements made per year since 1991, and a decrease in the percentage of measurements by year that exceeded the OSHA permissible exposure limits (PELs). Linear regression analyses detected decreasing trends in the geometric mean concentrations by year for 33 of the 36 agents analyzed. PMID- 11217722 TI - Development of a paperless, Y2K compliant exposure tracking database at Los Alamos National Laboratory. AB - The Industrial Hygiene and Safety Group at Los Alamos National Laboratory (LANL) developed a database application known as IH DataView, which manages industrial hygiene monitoring data. IH DataView replaces a LANL legacy system, IHSD, that restricted user access to a single point of data entry needed enhancements that support new operational requirements, and was not Year 2000 (Y2K) compliant. IH DataView features a comprehensive suite of data collection and tracking capabilities. Through the use of Oracle database management and application development tools, the system is Y2K compliant and Web enabled for easy deployment and user access via the Internet. System accessibility is particularly important because LANL operations are spread over 43 square miles, and industrial hygienists (IHs) located across the laboratory will use the system. IH DataView shows promise of being useful in the future because it eliminates these problems. It has a flexible architecture and sophisticated capability to collect, track, and analyze data in easy-to-use form. PMID- 11217723 TI - Future need for development of occupational exposure databases in Hungary. AB - The data on the occupational exposure measured by the hygienic network laboratories in Hungary were collected during the last 20 years. The data refer to the air pollutant chemicals and to the biological monitoring. The structure of the database of occupational exposure that has been used in the last decade is intended to be changed according to the guideline of the European Working Group on Exposure Registers in Europe. The current databases on the occupational exposure contain data only related to the substances responsible for air pollution. It would be desirable to complement the database with data from the biological monitoring, which also characterize the occupational exposure. It would then be possible to harmonize two distinct databases, and the risk assessment of the employees would become more thorough. This practice would require close cooperation of several organizations. It is desirable to set minimum requirements against the measurement techniques, thus, giving results that are accepted in the exposure database. It is necessary to encourage the use of direct reading instruments in collecting the exposure data and to complement the requirements of the strategies of data collection and the system of evaluation. PMID- 11217724 TI - Cleanup worker exposures to hazardous chemicals at a former nuclear weapons plant: piloting of an exposure surveillance system. AB - Cleanup of former U.S. Department of Energy (DOE) nuclear weapons production facilities involves potential exposures to various hazardous chemicals. We have collaboratively developed and piloted an exposure database and surveillance system for cleanup worker hazardous chemical exposure data with a cleanup contractor at the Rocky Flats Environmental Technology Site (RFETS). A unique system feature is the incorporation of a 34-category work task-coding scheme. This report presents an overview of the data captured by this system during development and piloting from March 1995 through August 1998. All air samples collected were entered into the system. Of the 859 breathing zone samples collected, 103 unique employees and 39 unique compounds were represented. Breathing zone exposure levels were usually low (86% of breathing zone samples were below analytical limits of detection). The use of respirators and other exposure controls was high (87 and 88%, respectively). Occasional high-level excursions did occur. Detailed quantitative summaries are provided for the six most monitored compounds: asbestos, beryllium, carbon tetrachloride, chromium, lead, and methylene chloride. Task and job title data were successfully collected for most samples, and showed specific cleanup activities by pipe fitters to be the most commonly represented in the database. Importantly, these results demonstrate the feasibility of the implementation of integrated exposure database and surveillance systems by practicing industrial hygienists employed in industry as well as the preventive potential and research uses of such systems. This exposure database and surveillance system--the central features of which are applicable in any industrial work setting--has enabled one of the first systematic quantitative characterizations of DOE cleanup worker exposures to hazardous chemicals. PMID- 11217726 TI - The development of a prototype database for the voluntary reporting of occupational exposure data on chemicals. AB - A prototype occupational exposure database was developed as part of a study to retrospectively collect chemical exposure data from U.K. industry. The data dictionary for the database was constructed using existing recommendations on core data elements developed by working groups from the ACGIH and the European Union. The study also made use of existing job and workplace coding schemes. The practicalities of gathering the data by voluntary donation, its storage in a database, and the transfer of suitably anonymised data to the U.K. Health and Safety Executive's National Exposure Database system were investigated and assessed. Prior to the development, several existing exposure database systems were evaluated for their suitability to store the data from the study. Though of high quality, these were found to be insufficiently flexible for the diversity of datasets encountered and so the prototype exposure database was constructed using a leading database development package. The database was successfully used to gather data and forward it in a suitable format to the U.K. Health and Safety Executive. The published recommendations on occupational exposure databases and the associated coding schemes provided a very useful foundation for designing and implementing the prototype database. However, as data collection proceeded it became clear that the existing recommendations often were poorly understood and misinterpreted, or at least interpreted differently, by different database designers, data collectors, and other users of occupational exposure data. It is suggested that several items in the ACGIH and European Union core recommendations are ambiguous and need to be clarified. Once agreed, the improved database design criteria need to be widely promoted to foster a common understanding and to encourage their use by all those involved in collecting occupational exposure data. Beyond this, recommendations for exposure databases should be augmented to facilitate easy exchange of data between organizations. PMID- 11217725 TI - Development of an occupational illness and injury surveillance database for the electric energy sector. AB - Currently available occupational injury and illness data for electric energy companies provide only overall summary rates. Specific information about types of injury or illnesses, rates by occupational or work environments, and injury costs and severity are generally not readily available. Relevant data such as personnel and claims information are frequently not integrated into a comprehensive health and safety surveillance system suitable for epidemiologic and health and safety research purposes. Epidemiological methods are valuable for identifying key risk factors for work-related injuries and illnesses and assessing their magnitude, as well establishing priorities for health and safety research. Application of such methods can result in long-term reductions in injury and illness rates and their attendant costs. Aggregation of relevant health and safety data across companies improves statistical power for the assessment of rare (yet costly) injuries or illness or specific at-risk subgroups within the electric energy sector. A pilot occupational injury and illness database has been developed that can incorporate and standardize data across a spectrum of companies of differing sizes and configurations. In illustrative data analyses, injury trends were summarized by company size, occupation, and demographic factors, among others. Trends observed in these illustrative analyses were consistent with results previously reported in the epidemiological literature, however, results are considered preliminary pending development of the full database. This study shows that development of a standardized surveillance occupational injury and illness database across companies with different database configurations is feasible. This database will ultimately provide a stable and accurate occupational health and safety assessment tool not currently available for this sector. PMID- 11217727 TI - The European chemical industry's needs and expectations for workplace exposure data. AB - Current information on exposure data is characterized by its inconsistent quality and significant gaps. These are particularly apparent amongst small- and medium sized companies. The European Chemical Industry Council (CEFIC), through its Long Range Research Initiative (LRI), currently is developing a tool which aims, by virtue of it being seen as an integral part of business management software, to collect relevant exposure information across key sectors of the chemical industry. PMID- 11217728 TI - Workshop on harmonization of serving multiple needs with occupational exposure databases, session II. PMID- 11217729 TI - Workshop on harmonization of serving future needs with occupational exposure databases--inhalation modeling, session IIIA. AB - This workshop was one of several that took place at the International Symposium on Occupational Exposure Databases and Their Application for the Next Millennium held in London from November 1-3, 1999. About 30 delegates participated in the workshop. The agenda for the discussions was provided by a white paper prepared by the organizers. The workshop produced a conceptual outline for a general purpose prediction model for inhalation exposure, and constructed a list of important input variables for successful model development. Evaluation of prototype models was discussed in some detail, and the workshop concluded with suggestions for taking forward the ideas discussed and maintaining the momentum and interest generated during the symposium. PMID- 11217730 TI - Occupational exposure information needs for regulatory risk assessment of existing chemicals. PMID- 11217731 TI - Comparison of fluorescence and rinsing methods for assessing dermal exposure. AB - There are a number of methods of estimating dermal contamination. "Potential exposure" methods, such as patch and whole-body oversuit sampling, intercept the contaminant before it reaches the skin. "Actual exposure" measurements recover the contaminant from the skin by wiping, stripping, or rinsing, or, in the case of fluorescent tracer dye monitoring, assess it in-situ on the skin. These different methods can give rise to very different results. Comparison of methods is difficult, because they usually interfere within-subject. This presentation is a comparison of two compatible 'actual dermal contamination' measurement techniques. They are: (1) fluorescence monitoring of a tracer dye in-situ on the skin, using ultraviolet light and a video camera linked to an image processor; (2) rinsing of the skin to recover a metal tracer salt for later assay in solution. Several painting and spraying application tasks were carried out by a panel of volunteers who wore T-shirts, shorts, and open sandals. The exercises simulated domestic or nonoccupational tasks. Results showed excellent agreement, with discrepancies identified and explained. The good agreement of the two completely different, independent tracer methods for measuring skin contamination contributes to their mutual validation. PMID- 11217732 TI - Assessment of dermal exposure--empirical models and indicative distributions. AB - The Health and Safety Executive embarked upon a program of work to address the issue of exposure to nonagricultural pesticides in the United Kingdom. Early on it became clear that the primary route of exposure was via the skin. Empirical dermal exposure models have been developed which allow estimates of potential dermal exposure to be derived from distributions of rate of contamination with in use formulations during typical use conditions in the workplace. Estimates of actual dermal exposure (what gets onto the skin) may also be anticipated and used in quantitative risk assessment to inform product registration. The key interpreted data from the empirical models are presented. Data are presented for six models. Separate summary data are presented for exposure to the body, hands, and feet. In the case of hand exposure, data are presented, in some cases, for contamination arising from wearing used (previously worn, of unknown history) and clean protective gloves. This article proposes a mechanism for addressing exposure assessment where little or no direct dermal exposure data are available- the indicative distribution approach. The empirical distributions of rate of contamination have been studied to seek commonalities which may allow the construction of a universal tool for use in screening level risk assessment. A simple 12-box matrix is proposed. PMID- 11217733 TI - Data solutions for the 21st century: CEFIC's vision and intentions. The European Chemical Industry Council. AB - Information on workplace exposures to chemicals has a role and importance that goes beyond compliance with occupational exposure limits (OELs). In particular, the increasing use of exposure data in regulatory risk assessment processes places added demands on the need to collect such information. Industry's challenge is to respond to these developments in a manner that ensures data are obtained, archived, and analyzed to standards consistent with evolving stakeholder expectations. PMID- 11217734 TI - Research recommendations of the NORA exposure assessment methods team. National Occupational Research Agenda. PMID- 11217735 TI - Personal protective equipment and dermal exposure. AB - Personal protective equipment (PPE) should only be used as a control measure when other measures are inappropriate or are inadequate by themselves. The person undertaking a risk assessment must exercise his or her judgment to take into account the protection afforded by the PPE. There is, therefore, considerable scope for differences in approach and it would seem sensible to eliminate these differences and ensure consistency, where possible, by reaching agreement on the attenuating effect of PPE. However, there is growing evidence that the levels of protection indicated by laboratory-based tests may not be achieved in real use situations. Studies of workplace protection suggest that the spread of contaminants inside protective clothing, including gloves, is commonplace and significant. Insufficient attention may have been paid to the effect of factors such as temperature differentials on the permeation of chemical agents through protective materials. To investigate this, a test cell was designed and built to measure the breakthrough times and subsequent permeation rate of solvents through glove materials where the temperature inside and outside the glove was representative of those that can occur in the workplace. Two chemical solvents were tested against two different glove materials at three different temperature conditions. The differences between the breakthrough times and permeation rates were measured and compared to manufacturer's test data. The practical implications are considered for risk of health and safety to the wearer. PMID- 11217736 TI - A field evaluation of the effect of pulsed arc welding technique on reducing worker exposures. PMID- 11217737 TI - A software application for implementing an effective industrial hygiene program, assisting with exposure assessment, and validating management indicators and performance metrics. PMID- 11217738 TI - A multidimensional electrospray MS-based approach to phosphopeptide mapping. AB - A new, multidimensional electrospray MS-based strategy for phosphopeptide mapping is described which eliminates the need to radiolabel protein with 32P or 33P. The approach utilizes two orthogonal MS scanning techniques, both of which are based on the production of phosphopeptide-specific marker ions at m/z 63 and/or 79 in the negative ion mode. These scan methods are combined with liquid chromatography electrospray mass spectrometry and nanoelectrospray MS/MS to selectively detect and identify phosphopeptides in complex proteolytic digests. Low-abundance, low stoichiometry phosphorylation sites can be selectively determined in the presence of an excess of nonphosphorylated peptides, even in cases where the signal from the phosphopeptide is indistinguishable from background in the conventional MS scan. The strategy, which has been developed and refined in our laboratory over the past few years, is particularly well suited to phosphoproteins that are phosphorylated to varying degrees of stoichiometry on multiple sites. Sensitivity and selectivity of the method are demonstrated here using model peptides and a commercially available phosphoprotein standard. In addition, the strategy is illustrated by the complete in vitro and in vivo phosphopeptide mapping of Sic1p, a regulator of the G1/S transition in budding yeast. PMID- 11217739 TI - Enhancement of the quality of MALDI mass spectra of highly acidic oligosaccharides by using a nafion-coated probe. AB - Spectra of highly acidic oligosaccharides obtained by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) can be greatly enhanced in quality by coating the MALDI probe surface with a film consisting of a perfluorosulfonated ionomer (Nafion) prior to the addition of the sample-matrix mixture. For comparison, three mixtures containing highly acidic oligo- and polysaccharides derived from partial acidic hydrolysis of alginate, pectin, or carboxymethyl cellulose (CMC) were analyzed by employing probes with an uncoated gold surface or a surface coated with a Nafion or nitrocellulose film. The negative ion-mode MALDI spectra of the oligouronates (oligomers containing mannuronic/guluronic and galacturonic acid residues) obtained using uncoated or nitrocellulose-coated probes consisted of a series of broad, multiple peaks. These multiple peaks were assigned to the molecular ions of the nondissociated [M - H]- and partially sodiated [MnNa - H]-, where n = 1, 2, or 3, oligomers. In contrast, the corresponding spectra obtained with Nafion-coated probes contained only a single series of sharp peaks originating from the molecular ions ([M - H] ) of nondissociated oligomers exhibiting chain lengths of as many as approximately 15 uronic acid residues. The Nafion coating was apparently capable of removing the sodium counterions remaining in the deposit of the sample-matrix mixture on the probe, thereby greatly enhancing the signal-to-noise ratios of the peaks in the spectra. In a similar manner, higher quality spectra could also be obtained by using Nafion-coated probes for analysis of the oligouronates and CMC oligomers by positive ion-mode MALDI-MS. PMID- 11217740 TI - In situ ATR-FT-IR kinetic studies of molecular transport and surface binding in thin sol-gel films: reactions of chlorosilane reagents in porous silica materials. AB - ATR-FT-IR spectroscopy was employed to study the kinetics of transport and binding within thin silica sol-gel films. Studies of transport of several nonbinding probe molecules n-heptane, toluene, and 2-propanol, showed that slow diffusion occurs within the micropores of the sol-gel films which could be modeled as a single-exponential accumulation in agreement with numerical models for diffusion in constricted pores. The rate of transport into the film was found to decrease for molecules that interact strongly with the silica surface, which is consistent with adsorption inhibiting the transport of molecules through the pores. In situ spectroscopic studies of surface reactions with diphenylchlorosilane (DP-SiCl) reveal that DPSiCl reacts quickly with surface water to form diphenylhydroxysilane (DPSiOH), the reactive species detected within the film. Analysis of the time-dependent infrared spectra reveals both transport and surface-binding steps in the reaction kinetics. From the magnitudes of the rate constants and the corresponding pure component spectra, it is determined that the surface-binding component is responsible for accumulation of most of the silane at the silica surface. Ex situ spectroscopic studies confirm that Si-O-Si bond formation occurs at room temperature in these sol-gel films. Studies of chlorosilane reactions at silica surfaces pretreated with triethylamine were conducted to investigate the influence of amines on this chemistry; it was determined that the amine enhances the transport of more reagent molecules to the silica surface while the intrinsic rate of the binding reaction is not significantly changed. PMID- 11217741 TI - Assessment of purity and screening of peptide libraries by nested ion mobility TOFMS: identification of RNase S-protein binders. AB - Combinatorial peptide synthesis in combination with affinity selection and high resolution ion mobility/time-of-flight mass spectrometry (IM/TOFMS) analysis has been used to investigate the binding of a series of 96 related eight-residue peptides (with the general sequence NH2-GX1X2FX3X4X5G-CO2H, where X1 = L, F, V, Y; X2 = N, F; X3 = E, V, T; X4 = V, L; X5 = V, L) to the ribonuclease S protein. A key advantage of this strategy is that the IM/ TOFMS approach allows the relative abundances of individual library components (including numerous sequence and structural isomers) to be characterized before and after screening. The relative binding interactions of different sequences are assessed by comparing IM/TOFMS data for those components that pass through the column (as well as those that bind) to data for the library prior to screening. The high-affinity sequences that are found in this study are compared with those selected from much larger combinatorial libraries. The results suggest that many expected sequences in the large libraries may be missing (e.g., due to issues such as failure of specific steps during the synthesis or differences in solubility). Comparison of the binding sequences obtained in these studies and those reported previously indicates that screening results from large libraries should be interpreted with caution. PMID- 11217742 TI - Alpha-cyano-4-hydroxycinnamic acid affinity sample preparation. A protocol for MALDI-MS peptide analysis in proteomics. AB - We present a new MALD1 sample preparation technique for peptide analysis using the matrix alpha-cyano-4-hydroxy-cinnamic acid (CHCA) and prestructured sample supports. The preparation integrates sample purification, based on the affinity of microcrystalline CHCA for peptides, thereby simplifying the analysis of crude peptide mixtures. Enzymatic digests can thus be prepared directly, without preceding purification. Prepared samples are homogeneous, facilitating automatic spectra acquisition. This method allows preparation of large numbers of samples with little effort and without the need for automation. These features make the described preparation suitable for cost-efficient high-throughput protein identification. Performance of the sample preparation is demonstrated with in situ proteolytic digests of human brain proteins separated by two-dimensional gel electrophoresis. PMID- 11217743 TI - A 384-well solid-phase extraction for LC/MS/MS determination of methotrexate and its 7-hydroxy metabolite in human urine and plasma. AB - A solid-phase extraction procedure, in a 384-well format, has been developed for methotrexate and its primary metabolite, 7-hydroxymethotrexate, in human urine and plasma. This format has not been utilized previously for solid-phase extraction of drugs from biological fluids. The 384-well plates contained a C-18 stationary phase bonded to silica particles which are incorporated into a glass fiber membrane. Methotrexate and 7-hydroxymethotrexate have been quantified across the curve range of 1 to 50 microg/mL and 50 to 1000 ng/mL, respectively, in urine and from 5 to 250 ng/mL and 5 to 100 ng/mL, respectively, in plasma. Both analytes are quantified by linear regression using 20-microL sample aliquots. Experiments to evaluate the influence of particle size, elution volume, and injection volume on signal intensity were conducted and are reported, along with the results of experiments examining cross contamination between wells. Recovery was determined to be > or = 95% from urine. Results from a run of 384 samples analyzed over a 14-h period indicate that 384-well SPE can be successfully utilized to increase analytical run sizes and sample throughput for LC/MS/MS determination of small drug molecules in biological samples. PMID- 11217744 TI - Chromatographic interactions between proteins and sulfoalkylbetaine-based zwitterionic copolymers in fully aqueous low-salt buffers. AB - Macroporous monoliths containing N,N-dimethyl-N-methacryloyloxyethyl-N-(3 sulfopropyl)ammonium betaine (SPE) have been synthesized via in situ photopolymerization, yielding a stoichiometric balance between sulfur and nitrogen in the final polymer, which is indicative of a genuine strong/strong zwitterionic character. The chromatographic properties of these zwitterionic resins were evaluated with respect to the retention behavior of inorganic ions and proteins. The weak electrostatic nature of the interaction between the sulfobetaine monoliths and proteins provided a high selectivity between basic proteins and peptides. Elution was accomplished with low-ionic-strength fully aqueous mobile phases, whereby high recovery was obtained, even for hydrophobic proteins. Chaotropic ions such as perchlorate or thiocyanate were used as mobile phase modifiers to modulate the apparent ion exchange group density, thus introducing a route for the modulation of the ionic strength that is required to competitively elute the protein. The promising features of polymeric sulfoalkylbetaine interaction layers for separation and analysis of biological extracts was also manifested in an application involving purification of biologically active peptide-pheromone obtained from Enterococcus faecium. PMID- 11217745 TI - An inductively coupled plasma carbon emission detector for aqueous carbohydrate separations by liquid chromatography. AB - An inductively coupled plasma atomic emission spectrometer is used to detect carbon-containing compounds following separation by high-performance liquid chromatography. A calcium form ligand exchange column with distilled and deionized water as the mobile phase is used to separate carbohydrates. The eluting species are detected by monitoring the carbon atomic emission line at 193.09 nm. The mass detection limits using a photomultiplier tube for sucrose and glucose are 50 ng, while that for fructose is 60 ng. The carbon emission detector should provide the same detection limit for any compound with a similar mass percent of carbon, whether or not the compound exhibits appreciable absorption characteristics. While the carbon emission detector will universally detect any organic compound, it will discriminate against species with high molar absorptivity that may be present at low concentration. Such species may act as interferences in chromatograms generated with conventional UV-visible absorption detectors. To demonstrate the utility of the carbon emission detector, three sugars (glucose, fructose, sucrose) are determined in apple, crangrape, and orange juice. PMID- 11217746 TI - Improved analysis of dissolved carbohydrates in stream water with HPLC-PAD. AB - This paper describes improvements made to the determination of dissolved carbohydrates in stream water with high-performance liquid chromatography and pulsed amperometric detection (HPLC-PAD). We eliminated interference from dissolved oxygen, separated xylose and mannose along with other molecules, reduced the chromatographic peak shift associated with carbonate accumulation in the column to less than 1% for all samples, and achieved an 8% increase in recovery of hydrolyzed carbohydrates by replacing ion-exchange desalting cartridges with evaporative removal of HCl under N2. These modifications lowered detection limits to less than or equal to 0.4 nM for 10 different monosaccharides and enhanced our ability to follow the dynamics of these molecules in stream ecosystems. In the determination of dissolved free monosaccharides, average relative precision was 1.3% and recovery ranged from 92 to 109%. For dissolved total saccharides, average relative precision was 3.3%. Concentrations were stable when filtered (0.2 microm) stream water was stored for 1 day at 22 degrees C, 1 week at 4 degrees C, or 1.5 months at -20 degrees C. PMID- 11217747 TI - Optical sensors for detection of bacteria. 1. General concepts and initial development. AB - The concept of using immobilized nucleic acid stains as detection chemistry to fabricate optical bacterial sensors is first demonstrated. SYTO 13 (a green fluorescent cell stain) is used as the molecular recognition element and fluorescent reporter in the sensor. The sensor responds to aqueous and aerosolized bacterial samples in 15 and 30 min, respectively. In addition, the sensor can discriminate a change in Pseudomonas aeruginosa (Pa) cell concentration of 1 order of magnitude or less and can detect down to 2.4 x 10(5) cells/mL of Pa cells. The utility of the sensor is demonstrated by monitoring the growth of a Pa cell culture over a period of 50 h. PMID- 11217748 TI - Enhanced detection of live bacteria using a dendrimer thin film in an optical biosensor. AB - Here we describe the detection of live Pseudomonas aeruginosa using a sensing film containing a fourth-generation hydroxy-terminated polyamidoamine (PAMAM) dendrimer (i.e., G4-OH) and SYTOX Green fluorescent nucleic acid stain. The films are configured on simple, disposable plastic coupons or optical fibers and are interrogated using a miniature fiber-optic spectrometer. SYTOX Green is generally considered a dead cell stain because it is not able to cross the membranes of live cells. In the presence of PAMAM-OH (G4-OH) in water, the bacterial cell becomes permeable to the SYTOX dye and the fluorescence is significantly enhanced. The fluorescence increases with the bacteria concentration, and the intensity at 5.4 x 10(7) cells mL(-1) is 350% higher than the liquid controls without PAMAM-OH. We also demonstrate that dendrimers stabilize the sensing film. After drying and desiccation, the SYTOX Green/PAMAM-OH films are still able to quantitatively detect P. aeruginosa in water. Incorporation of glucose into the SYTOX Green/ PAMAM-OH film may improve the homogeneity of the film and enhances the fluorescence signal an additional 11-25%. PMID- 11217749 TI - A quantitative assessment of heterogeneity for surface-immobilized proteins. AB - Many biotechnological applications use protein receptors immobilized on solid supports. Although, in solution, these receptors display homogeneous binding affinities and association/dissociation kinetics for their complementary ligand, they often display heterogeneous binding characteristics after immobilization. In this study, a fluorescence-based fiber-optic biosensor was used to quantify the heterogeneity associated with the binding of a soluble analyte, fluorescently labeled trinitrobenzene, to surface-immobilized monoclonal anti-TNT antibodies. The antibodies were immobilized on silica fiber-optic probes via five different immobilization strategies. We used the Sips isotherm to assesses and compare the heterogeneity in the antibody binding affinity and kinetic rate parameters for these different immobilization schemes. In addition, we globally analyzed kinetic data with a two-compartment transport-kinetic model to analyze the heterogeneity in the analyte-antibody kinetics. These analyses provide a quantitative tool by which to evaluate the relative homogeneity of different antibody preparations. Our results demonstrate that the more homogeneous protein preparations exhibit more uniform affinities and kinetic constants. PMID- 11217750 TI - Design and validation of portable SPME devices for rapid field air sampling and diffusion-based calibration. AB - The use of SPME fibers coated with porous polymer solid phases for quantitative purposes is limited due to effects such as interanalyte displacement and competitive adsorption. For air analysis, these problems can be averted by employing short exposure times to air samples flowing around the fiber. In these conditions, a simple mathematical model allows quantification without the need of calibration curves. This work describes two portable dynamic air sampling (PDAS) devices designed for application of this approach to nonequilibrium SPME sampling and determination of airborne volatile organic compounds (VOCs). The use of a PDAS device resulted in greater adsorbed VOC mass compared to the conventional SPME extraction in static air for qualitative screening of live plant aromas and contaminants in indoor air. For all studied air samples, an increase in the number of detected compounds and sensitivity was also observed. Quantification of aromatic VOCs in indoor air was also carried out using this approach and the PDAS/SPME device. Measured VOC concentrations were in low parts-per-billion by volume range using only 30-s SPME fiber exposure and were comparable to those obtained with a standard NIOSH method 1501. The use of PDAS/SPME devices reduced the total air sampling and analysis time by several orders of magnitude compared to the NIOSH 1501 method. PMID- 11217751 TI - Chemiluminescence imaging ELISA using an imprinted polymer as the recognition element instead of an antibody. AB - An imaging assay analogous to competitive enzyme immunoassays has been developed using a molecularly imprinted polymer instead of an antibody. The antigen 2,4 dichlorophenoxyacetic acid (2,4-D) was labeled with tobacco peroxidase, and the chemiluminescence reaction of luminol was used for detection. Microtiter plates (96 or 384 wells) were coated with polymer microspheres imprinted with 2,4-D, which were fixed in place by using poly(vinyl alcohol) as glue. In a competitive mode, the analyte-peroxidase conjugate was incubated with the free analyte in the microtiter plate, after which the bound fraction of the conjugate was quantified. After addition of the chemiluminescent substrates, light emission was measured in a high-throughput imaging format with a CCD camera. Calibration curves corresponding to analyte concentrations ranging from 0.01 to 100 microg/mL were obtained. PMID- 11217752 TI - Lysing bacterial spores by sonication through a flexible interface in a microfluidic system. AB - Cell disruptions using ultrasonic energy transmitted through a flexible interface into a liquid region has limitations because the motion of the vibrating tip is not completely transferred into the liquid. To ensure that some degree of contact will be maintained between the ultrasonic horn tip and the flexible interface, the liquid must be pressurized. The pressure conditions that yield consistent coupling between the ultrasonic horn tip and the liquid region were explored in this study by using an analytical model of the system and test fixture experiments. The nature of the interaction between the horn tip and the flexible interface creates pulses of positive pressure rises, increase in temperature, streaming flow, and almost no cavitation in the liquid. There was sufficient energy to create a cloud of microspheres, or beads, that maintain a consistent pattern of ballistic motion in the liquid. The sonication was found to be repeatable by studying video recordings of bead motion and was shown to be statistically consistent using measurements of temperature rise. Sonication of bacterial spores to obtain measurements of released nucleic acid and SEM images of damaged spores were used to verify the effects of liquid pressure on the horn interface-liquid coupling. PMID- 11217753 TI - MicroITIES detection of nitrate by facilitated ion transfer. AB - A microITIES array, created by laser photoablation of a 12-microm polyester film, was used to investigate electroassisted anion transfer between two immiscible electrolyte solutions. Besides measuring directly the transfer of nitrate to the organic phase, the enhancement of transfer of the cation (K+) by facilitated anion (counterion) transfer was measured as well. In the presence of a triamide derived from tris(2-aminoethyl)amine (tren), which is known to function as a host for nitrate, the current responses for both nitrate and potassium transfer were monitored. The linear relationships between the current responses and nitrate concentration formed the basis of an anion sensor with a dynamic range from 0.1 to 5 mM. A dual facilitated transfer mechanism is proposed to explain the enhancement phenomenon. PMID- 11217754 TI - Dispersion reduction in pressure-driven flow through microetched channels. AB - Fluid is often moved about microetched channels in lab-on-a-chip applications using electrokinetic flows (electrophoresis or electroosmosis) rather than pressure-driven flows because the latter result in large Taylor dispersion. However, small pressure gradients may arise unintentionally in such systems due to a mismatch in electroosmotic flow rates or hydrostatic pressure differentials along the microetched channel. Under laminar flow conditions, Doshi et al. (Chem. Eng. Sci. 1978, 33, 795-804) have shown that for a channel with rectangular cross section of width W and depth d, longitudinal diffusivities can attain values as large as approximately 8 K0 for small values of the aspect ratio d/W, where K0 is the value of the longitudinal diffusivity obtained by ignoring all variations across the channel. Microchannels in lab-on-a-chip geometries are often not rectangular in cross-section. Isotropic etching techniques, for example, lead to channels with quarter-circular ends. In this paper we examine the effect of this geometry on the magnitude of longitudinal dispersivity for pressure-driven flows and also investigate modifications to this design which may minimize such dispersion. Optimal channel profiles are shown to lead to dispersivities approaching K0, the theoretical minimum, for small values of d/W. PMID- 11217755 TI - Voltammetric determination of L-cysteine at conductive diamond electrodes. AB - Boron-doped diamond (BDD) electrodes were used to examine L-cysteine (CySH) oxidation in alkaline media. The results of the voltammetric and polarization measurements showed that at BDD electrodes the overall CySH oxidation reaction is controlled by the initial electrochemical step, i.e., the oxidation of the CyS- electroactive species. The same conclusion was supported by the results of a study of pH effects. Conversely, at glassy carbon (GC) electrodes, the same reaction is controlled by the desorption of the reaction products. These results account for the poor response for CySH determination at GC compared to BDD. It was found that BDD exhibits excellent behavior for CySH determination, clearly outperforming GC. The results demonstrate that measurement of the peak current for CySH oxidation can be used as a basis for simple method for determining CySH in the micromolar concentration range by the use of BDD electrodes. PMID- 11217756 TI - Bias assessment of current technologies used for the determination of low levels of moisture in mineral oil samples. AB - The problem in the current debate on the accuracy of Karl Fischer (KF) titrations lies in the fact that coulometry is being compared to volumetry on mineral oil samples for which the true moisture content is unknown. To clarify this point, dehydrated oil samples equilibrated under known temperature and relative humidity conditions and equilibrated oil samples containing known amounts of added moisture were used to assess the accuracy of the determinations. In addition, the measurements were extended to other techniques given that it is unlikely that they would be affected by the same phenomenon causing the KF systematic errors. The samples sent to different laboratories were analyzed by headspace/capillary gas chromatography, gas-phase H2 sensor, oil-phase or gas-phase RH sensors, KF coulometric titration with direct or indirect injection, and KF volumetric titration using a standard or NIST modified procedure. The laboratory comparison showed that with the exception of 4 techniques out of 10 that were tested, the measurements gave results in the expected concentration range. Considering the exceptions, two techniques based on volumetric titration yielded results tainted with an important positive bias for both sample types. This bias, tentatively associated with the high iodine end point concentration used by these systems, was estimated at approximately 22 ppm under the conditions applied by NIST. On the other hand, the two RH sensors showed a marked tendency to underestimate the value of the samples containing high moisture content. In this case, a loss of analyte through wall adsorption during the time required to achieve steady-state conditions in the measuring chamber seems to be at the origin of the negative biases. PMID- 11217757 TI - Phase-sensitive detection in potential-modulated in situ absorption and probe beam deflection techniques: theoretical considerations. AB - A mathematical framework is presented for the quantitative analysis of in situ potential modulation spectroelectrochemical techniques based on phase-sensitive detection for the study of solution-phase redox systems under strict diffusion control. In the case of arrangements in which the probing beam is parallel to the electrode surface, the phase of the optical signal with respect to the applied potential, assuming negligible double-layer charging currents, was found to be proportional to y(omega/2D)(1/2), where y is the distance normal to the electrode, omega is the frequency of the perturbating signal, and D is the diffusion coefficient of the species responsible for absorption or refraction. Good agreement was found between theoretical predictions and the few available experimental results for both absorption and probe beam deflection-type experiments. In particular, in the case of solutions containing the chromophore trianisylamine and nonabsorbing p-benzoquinone, the phase angle difference between absorption and diffraction calculated from theory and measured experimentally yielded a common value of approximately 30 degrees. PMID- 11217758 TI - Scanning electrochemical microscopy of membrane transport in the reverse imaging mode. AB - Scanning electrochemical microscopy (SECM), operated in reverse imaging mode (RIM), has been used to visualize the steady-state transport of molecules entering into porous membranes. RIM imaging is advantageous for investigating transport across biological membranes in situations where the SECM tip can access only the exterior membrane surface. Examples of RIM images of a synthetic membrane (mica with pores filled with the ion-selective polymer Nafion) and a biological membrane (hairless mouse skin) recorded during diffusive and iontophoretic transport, are reported. RIM imaging during diffusive transport allows visualization of the depletion of solute molecules in the solution adjacent to the pore openings. However, an accumulation of solute molecules above the pore opening is observed during iontophoresis, which is a consequence of the separation of the solute from the solvent (i.e., ultrafiltration). The separation results from differences in the rates of molecule transfer across the pore/solution interface when electroosmotic flow is operative. The results suggest that RIM imaging may be useful for measuring the kinetics of interfacial molecule transfer at biological membranes. PMID- 11217759 TI - The postdoc: an opportunity for learning and more. PMID- 11217760 TI - The problem of uniqueness of fit for viscoelastic films on thickness-shear mode resonator surfaces. AB - We describe a new strategy for interpreting frequency responses of thickness shear mode resonators loaded with spatially uniform viscoelastic films. This procedure leads to unambiguous extraction of the four parameters that characterize such a film: its thickness, density and shear modulus components (storage and loss moduli). The interpretational difficulty is that the experimental frequency response (impedance spectrum) can only provide two parameters; thus, the problem is underdetermined. Previous interpretations employed various approximations and assumptions for two (or more) film parameters to effectively reduce the problem to a two-parameter fit. Such approaches are clearly imperfect. Our new strategy splits the problem into two separate two parameter sub-problems, each of which is solved by the measurement of two different experimental responses. The result is a unique fit to the data without the need to make approximations or assumptions for film parameters. First, in the acoustically thin regime, measured frequency shift and film charge are combined to provide a unique solution for film thickness and density; shear moduli components do not affect the response in this regime. Second, film density is carried forward directly, and the film thickness-charge relationship is extrapolated into the acoustically thick regime. Third, with film density and thickness held fixed, crystal impedance data in the acoustically thick regime provide unambiguous shear modulus components. The method is generalized to any other (nonelectrochemical) probe that provides film thickness data and validated using crystal impedance data for poly(3-methylthiophene) films exposed to propylene carbonate. PMID- 11217761 TI - Noncontact electrochemical imaging with combined scanning electrochemical atomic force microscopy. AB - Combined scanning electrochemical atomic force microscopy (SECM-AFM) is a recently introduced scanned probe microscopy technique where the probe, which consists of a tip electrode and integrated cantilever, is capable of functioning as both a force sensor, for topographical imaging, and an ultramicroelectrode for electrochemical imaging. To extend the capabilities of the technique, two strategies for noncontact amperometric imaging-in conjunction with contact mode topographical imaging-have been developed for the investigation of solid-liquid interfaces. First, SECM-AFM can be used to image an area of the surface of interest, in contact mode, to deduce the topography. The feedback loop of the AFM is then disengaged and the stepper motor employed to retract the tip a specified distance from the sample, to record a current image over the same area, but with the tip held in a fixed x-y plane above the surface. Second, Lift Mode can be employed, where a line scan of topographical AFM data is first acquired in contact mode, and the line is then rescanned to record SECM current data, with the tip maintained at a constant distance from the target interface, effectively following the contours of the surface. Both approaches are exemplified with SECM feedback and substrate generation-tip collection measurements, with a 10-microm diameter Pt disk UME serving as a model substrate. The approaches described allow electrochemical images, acquired with the tip above the surface, to be closely correlated with the underlying topography, recorded with the tip in intimate contact with the surface. PMID- 11217762 TI - Oxidation kinetics of guanine in DNA molecules adsorbed onto indium tin oxide electrodes. AB - Oligonucleotides containing the guanine nucleobase were adsorbed onto ITO electrodes from mixtures of DMF and acetate buffer. Chronocoulometry and chronoamperometry were performed on the modified electrodes in both phosphate buffer and buffer containing low concentrations of the inorganic complex Ru(bpy)3(2+) (bpy = 2,2' bipyridine), which catalyzes guanine oxidation. The charge and current evolution with and without the catalyst were compared to the charge and current evolution for electrodes that were treated with identical oligonucleotides that were substituted at every guanine with the electrochemically inert nucleobase hypoxanthine. Chronocoulometry over 2.5 s shows that roughly 2 electrons per guanine were transferred to the electrode in both the presence and absence of Ru(bpy)3(2+), although at a slower rate for the uncatalyzed process. Chronoamperograms measured over 250 ms can be fit to a double exponential decay, with the intensity of the fast component roughly 6-20 times greater than that of the slow component. First- and second-order rate constants for catalytic and direct guanine oxidation were determined from the fast component. The maximum catalytic enhancement for immobilized guanine was found to be i(cat)/i(d) = 4 at 25 microM Ru(bpy)3(2+). The second-order rate constant for the catalyzed reaction was 1.3 x 10(7) M(-1) s(-1), with an apparent dissociation constant of 8.8 microM. When compared to parallel studies in solution, a smaller value of the dissociation constant and a larger value of the second-order rate constant are observed, probably due to distortion of the immobilized DNA, an increase in the local negative charge due to the oxygen sites on the ITO surface, and redox cycling of the catalyst, which maintains the surface concentration of the active form. PMID- 11217763 TI - Death, taxes, and analytical chemistry. PMID- 11217764 TI - Single-molecule DNA amplification and analysis in an integrated microfluidic device. AB - Stochastic PCR amplification of single DNA template molecules followed by capillary electrophoretic (CE) analysis of the products is demonstrated in an integrated microfluidic device. The microdevice consists of submicroliter PCR chambers etched into a glass substrate that are directly connected to a microfabricated CE system. Valves and hydrophobic vents provide controlled and sensorless loading of the 280-nL PCR chambers; the low volume reactor, the low thermal mass, and the use of thin-film heaters permit cycle times as fast as 30 s. The amplified product, labeled with an intercalating fluorescent dye, is directly injected into the gel-filled capillary channel for electrophoretic analysis. Repetitive PCR analyses at the single DNA template molecule level exhibit quantized product peak areas; a histogram of the normalized peak areas reveals clusters of events caused by 0, 1, 2, and 3 viable template copies in the reactor and these event clusters are shown to fit a Poisson distribution. This device demonstrates the most sensitive PCR possible in a microfabricated device. The detection of single DNA molecules will also facilitate single-cell and single molecule studies to expose the genetic variation underlying ensemble sequence and expression averages. PMID- 11217765 TI - MS/NMR: a structure-based approach for discovering protein ligands and for drug design by coupling size exclusion chromatography, mass spectrometry, and nuclear magnetic resonance spectroscopy. AB - A protocol is described for rapidly screening small organic molecules for their ability to bind a target protein while obtaining structure-related information as part of a structure-based drug discovery and design program. The methodology takes advantage of and combines the inherent strengths of size exclusion gel chromatography, mass spectrometry, and NMR to identify bound complexes in a relatively universal high-throughput screening approach. Size exclusion gel chromatography in the spin column format provides the high-speed separation of a protein-ligand complex from free ligands. The spin column eluent is then analyzed under denaturing conditions by electrospray ionization mass spectrometry (MS) for the presence of small molecular weight compounds formerly bound to the protein. Hits identified by MS are then individually assayed by chemical shift perturbations in a 2D 1H-15N HSQC NMR spectrum to verify specific interactions of the compound with the protein and identification of the binding site on the protein. The utility of the MS/NMR assay is demonstrated with the use of the catalytic fragment of human fibroblast collagenase (MMP-1) as a target protein and the screening of a library consisting of approximately 32 000 compounds for the identification of molecules that exhibit specific binding to the RGS4 protein. PMID- 11217766 TI - A four-column parallel chromatography system for isocratic or gradient LC/MS analyses. AB - A novel approach to parallel liquid chromatography/ tandem mass spectrometry (LC/MS/MS) analyses for pharmacokinetic assays and for similar quantitative applications is presented. Modest modifications render a conventional LC/MS system capable of analyzing samples in parallel. These modifications involve the simple incorporation of three valves and four LC columns into a conventional system composed of one binary LC pumping system, one autosampler, and one mass spectrometer. An increase in sample throughput is achieved by staggering injections onto the four columns, allowing the mass spectrometer to continuously analyze the chromatographic window of interest Using this approach, the optimized run time is slightly greater than the sum of the widths of the desired peaks. This parallel chromatography unit can operate under both gradient and isocratic LC conditions. To demonstrate the utility of the system, atorvastatin, five of its metabolites, and their deuterated internal standards (IS) were analyzed using gradient elution chromatography conditions. The results from a prestudy assay evaluation (PSAE) tray of standards and quality control (QC) samples from extracted spiked human plasma are presented. The relative standard deviation and the accuracy of the QC samples did not exceed 8.1% and 9.6%, respectively, which is well within the acceptance criteria of the pharmaceutical industry. For this particular analysis, the parallel chromatography system decreased the overall run time from 4.5 to 1.65 min and, therefore, increased the overall throughput by a factor of 2.7 in comparison to a conventional LC/MS/MS analytical method. PMID- 11217767 TI - Exact mass measurements on-line with high-performance liquid chromatography on a quadrupole mass spectrometer. AB - Exact mass measurements were performed on-line with high-performance liquid chromatography on a quadrupole mass spectrometer. Compounds with molecular weights from 98 to 797, mainly aromatic sulfonates and sulfonamides, were analyzed with electrospray ionization in positive or negative mode. Internal mass calibration compounds were continuously added after separation. A Gaussian fit of the mass errors of 808 individual measurements (concentrations of 1-10 mg/L, 20 200 ng absolute on column) resulted in a mean error of 0.1 mmu (0.45 ppm) and a standard deviation sigma of 1.5 mmu (5.4 ppm). The 99.7% confidence intervals (3sigma) were +/-4.5 mmu (+/-16.2 ppm) for single mass measurements. Averaging 10 measurements further reduced the errors to less than +/-1.5 mmu (+/-5 ppm). Isobaric interferences with ions resulting from the mass calibrants were avoided by the use of complementary mass calibrants. The results were verified (differences below +/-4.5 mmu) with a LC/ oa-TOFMS. Limited mass range chromatograms were used to enhance selectivity in the analysis of mixtures. The method was applied to determine the elemental composition of a potential dye metabolite detected in anaerobically treated textile wastewater. PMID- 11217768 TI - Application of quantitative chemometric analysis techniques to direct sampling mass spectrometry. AB - This paper explores the use of direct sampling mass spectrometry coupled with multivariate chemometric analysis techniques for the analysis of sample mixtures containing analytes with similar mass spectra. Water samples containing varying mixtures of toluene, ethyl benzene, and cumene were analyzed by purge-and trap/direct sampling mass spectrometry. Multivariate calibration models were built using partial least-squares regression (PLS), trilinear partial least squares regression (tri-PLS), and parallel factor analysis (PARAFAC), with the latter two methods taking advantage of the differences in the temporal profiles of the analytes. The prediction errors for each model were compared to those obtained with simple univariate regression. Multivariate quantitative methods were found to be superior to univariate regression when a unique ion for quantitation could not be found. For prediction samples that contained unmodeled, interfering compounds, PARAFAC outperformed the other analysis methods. The uniqueness of the PARAFAC model allows for estimation of the mass spectra of the interfering compounds, which can be subsequently identified via visual inspection or a library search. PMID- 11217769 TI - Determination of low molecular weight silicones in plasma and blood of women after exposure to silicone breast implants by GC/MS. AB - A sensitive, one-step sample preparation method for detection of volatile, low molecular weight (LMW) cyclic silicones hexamethylcyclotrisiloxane (D3), octamethyl-cyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5), and dodecamethylcyclohexasiloxane (D6) in plasma and blood using gas chromatography coupled with mass spectrometry (GC/MS, SIM mode) is presented. In spiked experiments, extraction efficiencies for these siloxanes (100-20 000 ng/mL) were approximately 90% for plasma and approximately 80% for blood; only in the case of D3 was the recovery very low. Plasma and blood of women who are or were exposed to silicone gel-filled implants and of control subjects were analyzed for low molecular weight silicones. D3-D6 were not detectable in control plasma or blood. Although the investigated numbers of patients samples are very limited, and thus, no statistical analysis is possible, our data clearly show a general increase in the amount of LMW cyclic siloxanes in the bodies of women with silicone implants. In particular, several years after ruptured silicone implants were removed, siloxanes could still be found in blood samples from several women. Siloxane compound D3 varied between 6 and 12 ng/mL (plasma) and between 20 and 28 ng/mL (blood), whereas the concentration range of D4 was 14-50 ng/mL (plasma) and 79-92 ng/mL (blood). D5 and D6, with one exception, could not be detected. PMID- 11217770 TI - Porous silicon as a versatile platform for laser desorption/ionization mass spectrometry. AB - Desorption/ionization on porous silicon mass spectrometry (DIOS-MS) is a novel method for generating and analyzing gas-phase ions that employs direct laser vaporization. The structure and physicochemical properties of the porous silicon surfaces are crucial to DIOS-MS performance and are controlled by the selection of silicon and the electrochemical etching conditions. Porous silicon generation and DIOS signals were examined as a function of silicon crystal orientation, resistivity, etching solution, etching current density, etching time, and irradiation. Pre-and postetching conditions were also examined for their effect on DIOS signal as were chemical modifications to examine stability with respect to surface oxidation. Pore size and other physical characteristics were examined by scanning electron microscopy and Fourier transform infrared spectroscopy, and correlated with DIOS-MS signal. Porous silicon surfaces optimized for DIOS response were examined for their applicability to quantitative analysis, organic reaction monitoring, post-source decay mass spectrometry, and chromatography. PMID- 11217771 TI - Genotyping of two mutations in the HFE gene using single-base extension and high performance liquid chromatography. AB - Currently, a major focus of human genetics is the utilization of single nucleotide polymorphisms for clinical diagnostics, whole-genome linkage disequilibrium screens to identify common disease genes such as Alzheimer disease, determination of the recent evolutionary history of a species, and the process of speciation. We have examined single-nucleotide extension coupled with high-performance liquid chromatography as a method to simultaneously genotype two SNPs occurring in the coding region of the HFE gene that produce clinical effects. This assay allows concurrent genotyping of the C282Y and H63D mutations in 11 min and is 100% concordant with current testing methods for both of these mutations. PMID- 11217772 TI - A solid sample preparation method that reduces signal suppression effects in the MALDI analysis of peptides. AB - Here we report on the application of a solid-solid (SS) sample preparation protocol for the MALDI analysis of peptides and multicomponent peptide mixtures. Our results with a series of model peptides indicate that a SS MALDI sample preparation protocol is useful for the analysis of peptides in the 1-3 kDa mass range. MALDI mass spectra recorded for peptides in this size range using a SS sample preparation were of a quality comparable to spectra recorded using a conventional dried-droplet (DD) sample preparation. Our results with several model peptide mixtures indicate that one advantage of a SS sample preparation protocol for the MALDI analysis of peptides is that it can significantly reduce signal suppression effects in multicomponent mixtures. MALDI results obtained using a SS sample preparation protocol are also more reproducible than results obtained using a conventional DD sample preparation protocol. PMID- 11217773 TI - Electrospray device for coupling microscale separations and other miniaturized devices with electrospray mass spectrometry. AB - A miniaturized ion sprayer device is described which is suitable for coupling with chip-based analytical separation devices, multiwell plates, or surfaces containing residues of prepared samples. Two versions of a similar device are described. A "microsprayer" device suitable for coupling to the terminal edge of a capillary electrophoresis (CE) chip is constructed from modified 1/16-in. HPLC fittings. This microsprayer employs a free-standing liquid junction formed via continuous delivery of a flow (2-6 microL/min) of suitable solvent which carries the CE effluent through a pneumatically assisted electrospray (ion spray) needle positioned in front of an atmospheric pressure ionization (API) mass spectrometer. A related but larger "minisprayer" device is also described which employs the same features as the microsprayer, but with an extended sampling capillary tube which can reach into the depths of 96-, 384-, and 1536-multiwell plates containing either sample solutions or dried sample residues. The minisprayer may be positioned in front of an API ion sampling orifice and the multiwell plate positioned stepwise from sample to sample for analysis of trace samples contained in the wells. The resulting infusion-ion spray mass spectrometric analyses can provide sequential analysis of previously prepared biological samples containing small drug compounds, proteins, and related compounds. This same device is also shown to be useful for sampling from a surface containing trace level compounds of biological interest. Results are shown that demonstrate microscale separations and selected ion monitoring (SIM) capillary electrophoresis/mass spectrometry (CE/MS) detection of berberine and palmatine using the microsprayer. SIM ion spray determination of a 2 ng/microL solution of berberine contained as a dry residue in the bottom of a 384-well plate as well as full-scan electrospray mass spectra for low-picomole levels of cytochrome c contained in a 1536-well microtiter plate are shown. The respective micro- and minisprayer devices provide a simple yet effective means of transferring trace-level samples either from a microscale or chip-based separation device as well as samples contained in multiwell plates which are increasingly employed in high-throughput applications in the pharmaceutical industry. PMID- 11217774 TI - Chip-based capillary electrophoresis/mass spectrometry determination of carnitines in human urine. AB - A chip-based capillary electrophoresis/mass spectrometry (CE/MS) system is described for the CE separation and on-line electrospray detection of carnitine and selected acylcarnitines from mixtures of analytical standards as well as extracts of fortified human urine. Chip-based CE/MS experiments in two different laboratories were carried out using a triple-quadrupole mass spectrometer and a quadrupole time-of-flight (QTOF) mass spectrometer, respectively. The glass chips used with both systems were comparably equipped with a microfabricated capillary electrophoresis (CE) channel but with different electrosprayers. The quadrupole chip-based CE/MS experiments employed a miniature coupled microsprayer, which allowed coupling of the microelectrospray process via a micro liquid junction at the exit of the CE capillary channel. Selected ion monitoring (SIM) CE/MS experiments were employed for all of the quadrupole CE/MS work. The QTOF CE/MS full-scan single MS and MS/MS experiments were carried out in another laboratory using accurate mass measurement TOF mass spectrometry techniques. The electrospray process that was employed with the QTOF system differed in that an inserted nanoelectrospray capillary needle was carefully affixed into a flat bottomed hole that was aligned with the CE channel exit orifice. SIM CE/MS using the described quadrupole system provided acceptable ion current electropherograms from fmole levels from analytical standard solutions of carnitine and acylcarnitines that were manually injected (loaded) onto the chip. In addition, the corresponding electropherograms for human urine fortified with the target carnitine and acylcarnitines at a 10-20 microg/mL (35-124 microM) level were obtained via SIM CE/MS techniques. The measured CE separation efficiency for the SIM CE/MS electropherograms was determined to be 2860 plates (peak width at half height method or N = 5.54(T/WO.5(2)), and carnitine and three acylcarnitines were separated in less than 48 s. In contrast, using quadrupole-TOF technologies, the same samples could be diluted by a factor of 2-4 to obtain a comparable detector response for the target compounds. In the full-scan, single mass analyzer mode (m/z 150-500), the CE separation efficiency was measured to be 2600 plates, but mass measurement accuracy was less than 5.0 ppm for the quaternary cations. In the CE/MS/MS mode, full-scan collision-induced dissociation (CID) mass spectra were obtained with a mass accuracy of < or =10 ppm for the higher mass ions and < or =27 ppm for the lower mass product ions. These results demonstrate the feasibility for on-chip CE separation and electrospray mass spectrometric detection for these important compounds in synthetic mixtures, as well as in human urine extracts. PMID- 11217776 TI - Bar codes for combinatorial libraries. PMID- 11217775 TI - Baseline mass resolution of peptide isobars: a record for molecular mass resolution. AB - Baseline resolution of two peptides, RVMRGMR and RSHRGHR, of neutral monoisotopic mass, approximately 904 Da, has been achieved by microelectrospray ionization Fourier transform ion cyclotron resonance mass spectrometry at a mass resolving power of approximately 3 300 000. The elemental compositions of these molecules differ by N40 vs. S2H8 (0.000 45 Da), which is less than one electron's mass (0.000 55 Da)! This result establishes a new record for the smallest resolved mass difference between any two molecules. This achievement is made possible by a combination of high magnetic field (9.4 T), large-diameter (4-in.) Penning trap, and low ion density. The implications for proteomics based on accurate mass measurements are discussed briefly. PMID- 11217777 TI - Negative-ion electrospray mass spectrometry of neutral underivatized oligosaccharides. AB - Negative-ion electrospray mass spectrometry (ES-MS) with collision-induced dissociation (CID) and MS/MS scanning on a quadrupole-orthoganal time-of-flight instrument provide a sensitive means for structural analysis of neutral underivatized oligosaccharides. Molecular mass information can be readily obtained from the dominant [M - H]- ions in the ES mass spectrum formed with subnanomole amounts of oligosaccharides, and similar sensitivity is available from CID-MS/MS to give structural details. The CID spectra of 14 oligosaccharides demonstrated that sequence and partial linkage information can be derived and isomeric structures can be differentiated. Series of C-type fragment ions give sequence information while the double glycosidic D-type cleavage of a 3-linked GlcNAc or Glc and the saccharide ring fragmentation of the 0,2A-type from 4 linked GlcNAc or Glc can provide partial linkage information. The distinctive D- and A-cleavages are important for differentiation of oligosaccharide type 1 and type 2 chains and to define the blood group H, Le(a), Le(x), Le(b), and Le(y) determinants carried by their fucosylated analogues. PMID- 11217778 TI - Formation of natural pH gradients in a microfluidic device under flow conditions: model and experimental validation. AB - A new isoelectric focusing technique has been developed that incorporates natural pH gradient formation in microfluidic channels under flowing conditions. In conjunction, a one-dimensional finite difference model has been developed that solves a system of algebraic-ordinary differential equations that describe the phenomena occurring in the system, including hydrolysis at the electrodes, buffering effects of weak acids and bases, and mass transport due to both diffusion and electrophoresis. A quantitative, noninvasive, optically based method of monitoring pH gradient formation is presented, and the experimental data generated by this method are found to be in good agreement with model predictions. In addition, the model provides a theoretical explanation for initially unexpected experimental results. Model predictions are also shown to match well with experimental results of microfluidic isoelectric focusing of a single protein species. Accounting for the nonuniform velocity profile, characteristic of pressure-driven flow in microfluidic channels, is found to improve predictions of dynamic pH changes close to the electrodes and overall time required to reach steady state, but to reduce the accuracy of dynamic pH change predictions in other regions of the channel. PMID- 11217779 TI - Combined HPLC-MS and HPLC-NMR on-line coupling for the separation and determination of lutein and zeaxanthin stereoisomers in spinach and in retina. AB - The determination and unambiguous identification of carotenoid stereoisomers from biological tissues, avoiding isomerization and oxidation due to the extraction process, is still a major challenge. Particularly, the analysis of lutein and zeaxanthin stereoisomers is of great importance, as these are the main constituents of the macula lutea, the central part of the human retina, and act as possible agents in the prevention and treatment of age-related macular degeneration (AMD). By combining a mild and quick extraction technique such as matrix solid-phase dispersion together with high-performance liquid chromatography (HPLC), the extremely light and oxygen sensitive lutein and zeaxanthin stereoisomers are extracted, enriched, and separated directly from the solid plant or tissue samples, excluding preparation of artifacts. HPLC separations are performed with C30 phases due to their enhanced shape selectivity compared to C18 phases and on-line coupled to mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. By using HPLC-MS with atmospheric pressure chemical ionization, the lutein stereoisomers can be distinguished from the zeaxanthin stereoisomers within one chromatographic run in the upper picogram range, whereas HPLC-NMR coupling allows the unequivocal identification of each stereoisomer with a concentration in the upper nanogram range. This article provides an analytical method for the artifact-free determination of lutein and zeaxanthin stereoisomers directly from the solid biological tissue spinach as a source of carotenoids and retina as the sphere of activity for AMD. In addition, the structures of these stereoisomers were unambiguously elucidated by employing hyphenated analytical techniques. PMID- 11217780 TI - Aggregating K+ sensor. PMID- 11217781 TI - Increasing the number of analyzable peaks in comprehensive two-dimensional separations through chemometrics. AB - Comprehensive two-dimensional (2-D) separations are emerging as powerful tools for the analysis of complex samples. The substantially larger peak capacity for a given length of time relative to 1-D separations is a well-known benefit of comprehensive 2-D separation methods. Unfortunately, with complex samples, the probability of peak overlap in 2-D separations is still quite high. This is especially true if one desires to speed up the analysis by reducing the run time and, thus, by reducing the resolving power along the first dimension separation. Chemometric methods hold considerable promise to overcome the limitations brought upon by the likelihood of peak overlap. Thus, chemometric methods should be able to effectively extend the resolving power of 2-D separation methods. In this paper, the theoretical enhancement provided by application of the generalized rank annihilation method (GRAM) for the analysis of unresolved peaks in comprehensive 2-D separations is carefully modeled and critically evaluated. First, Monte Carlo simulations are used to determine the conditions where the use of GRAM results in the successful analysis of unresolved peaks. A wide range of experimental conditions and performance criteria are modeled, typical to many available 2-D separation methods, including analyte/interference peak height ratio, first- and second-dimension resolutions, signal-to noise ratio, injection volume reproducibility, and run-to-run retention time reproducibility. Essentially, a wide range of experimental conditions and performance criteria are found to provide reliable data amenable to GRAM analysis. The information gleaned from this first set of simulations is then used in conjunction with Monte Carlo simulations of comprehensive 2-D separations. For these simulated 2-D separations, the total number of analyzable peaks when using GRAM was determined and found to be substantially better than using only traditional quantitative methods such as peak integration or height. For example, it was determined that the use of GRAM increases the average number of analyzable peaks by a factor of 2 for 2-D separations in which the peak capacity is 67% occupied by randomly distributed peaks. The results of the studies are general, and the use of GRAM should increase the number of analyzable peaks for all forms of comprehensive 2-D separations. PMID- 11217782 TI - Correlation of characteristic thermal constant and elution temperature in GC. AB - In a temperature-programmed analysis, the solutes that elute at higher temperatures have generally larger characterisitic thermal constants, theta(char). The change approximately matches the temperature-related increase in a carrier gas viscosity. Accounting for the effect allows reduction in the uncertainty of prediction of theta(char) by a factor or f approximately 2 and, in a constant-pressure mode, description of a linear heating ramp by the same dimensionless rate for all solutes. PMID- 11217783 TI - Synthesis of porous titania microspheres for HPLC packings by polymerization induced colloid aggregation (PICA). AB - Porous titania microspheres with a very narrow particle size distribution (PSD) were synthesized by polymerization-induced colloid aggregation (PICA). After being sintered, the titania microspheres that are obtained have an average diameter of 3.5 microm, a surface area of 36.7 m2/g, an average pore volume of 0.30 mL/g, and an average pore diameter of 32.2 nm. The microspheres possess enough rigidity to withstand high packing pressure and are very useful as a new kind of chromatographic packing material for high performance liquid chromatography (HPLC). PMID- 11217785 TI - MALDI chip shot. PMID- 11217786 TI - On-line particle concentrator with upstream ultrafiltration in continuous SPLITT fractionation. AB - An upstream ultrafiltration (UU) method is employed for the on-line concentration of collected particle fraction and for the convenient regulation of flow rates in split-flow thin (SPLITT) fractionation. Concentration of the collected particle fraction is necessary to fractionate particles by smaller cutoff diameters in SPLITT fractionation. By introducing a simple device utilizing upstream ultrafiltration with tangential flow, particle solution collected at each SP PMID- 11217784 TI - Enzyme-amplified aequorin-based bioluminometric hybridization assays. AB - The sensitivity of aequorin-based bioluminometric hybridization assays was enhanced by introducing, enzymically, multiple aequorin labels per DNA hybrid. The target DNA was hybridized in microtiter wells with an immobilized capture probe and a digoxigenin-labeled detection probe. The hybrids were reacted with an anti-digoxigenin antibody conjugated to horseradish peroxidase. Peroxidase catalyzed the oxidation of digoxigenin-tyramine by hydrogen peroxide, resulting in the attachment of multiple digoxigenin moieties to the solid phase. Aequorin labeled anti-digoxigenin antibody was then allowed to bind to the immobilized digoxigenins. The bound aequorin was determined by its characteristic Ca2+ triggered bioluminescence. As low as 20 fmol/L (1 amol/ well) target DNA was detected with a signal-to-background ratio of 2.7. A hybridization assay that used only aequorin-labeled anti-digoxigenin antibody without the peroxidase amplification step gave a signal-to-background ratio of 2 for 160 fmol/L target DNA. The signal enhancement of the amplified assay was in the range of 14-38 times. The analytical range of the amplified assay extended up to 2600 fmol/L. The CVs were in the range of 5.5-7.3%. PMID- 11217787 TI - Determination of peptides and proteins in fats and oils. AB - A method for the determination of proteins in fats and oils is described. Proteins were sequentially precipitated with acetone and hydrolyzed, and the produced amino acids were fractionated and quantificated. This analysis protocol afforded a method of high sensitivity and specificity which was fully evaluated and validated. The data obtained showed good accuracy and linearity with excellent reproducibility and recovery. When the method was applied to 40 olive oils, all of them contained proteins in the range 10-50 microg/100 g of oil, suggesting that proteins are nonpreviously described minor components of these oils. In addition, the proteins precipitated were almost exclusively composed by one polypeptide of apparent 4600 molecular weight, which was isolated from olive drupes and partially characterized by amino acid analysis. Similar polypeptides were also detected in other seeds, suggesting that they may constitute a new class of polypeptides in plants with oleosin-like characteristics. Furthermore, the method was also applied to different fats and oils, and all the samples analyzed contained proteins, suggesting that natural fats and oils always contain polypeptides and/or proteins as minor components. These results also suggest that some peptides are soluble in lipid matrixes, where they might be playing unknown functions. The developed procedure provides a methodology for the determination of these components. PMID- 11217788 TI - Determination of naphthenic acids in crude oils using nonaqueous ion exchange solid-phase extraction. AB - A method is presented for the routine, rapid, and quantitative analysis of aliphatic and naphthenic acids in crude oils, based on their isolation using nonaqueous ion exchange solid-phase extraction cartridges. The isolated acid fractions are methylated and analyzed by gas chromatography and gas chromatography/mass spectrometry. The method is effective on both light and heavy oils and is capable of providing mechanistic information of geochemical significance on the origin of the acids in the oils. Analysis of oils that were solvent extracted from laboratory and field mesocosm marine sediment oil degradation studies indicate that this new method of analyzing the products of hydrocarbon biodegradation may be a useful tool for monitoring the progress of bioremediation of oil spills in the environment. PMID- 11217790 TI - Collaboration pays off for NCSR. National Centre for Sensor Research. PMID- 11217789 TI - Fully automated 96-well liquid-liquid extraction for analysis of biological samples by liquid chromatography with tandem mass spectrometry. AB - A fully automated high-throughput liquid-liquid extraction (LLE) methodology has been developed for preparation of biological samples using a 96-well LLE plate and a 96-channel robotic liquid handling workstation. The 96-well LLE plate is made of a 96-well filter plate filled with inert diatomaceous earth particles, allowing continuous and efficient extraction of analytes between the aqueous biological sample and the organic extraction solvent. Two carboxylic acid-based protease inhibitor compounds with high and low levels of plasma protein binding were chosen for the development and application of the automated methodology. The LLE extracts of the plasma samples of the two compounds were analyzed by high performance liquid chromatography with electrospray (ESI) tandem mass spectrometry (LC-MS/MS). The LC-MS/MS method was developed using a rapid gradient LC separation, followed by sample introduction through an ionspray interface in the negative ion mode and tandem mass spectrometric detection with selected reaction monitoring. In the optimized LLE method, a formate buffer solution was first loaded into a 96-well filter plate packed with inert diatomaceous earth material. Then crude plasma samples and a water-immiscible organic solvent, methyl ethyl ketone, were sequentially added to the LLE plate so that LLE would occur in the interface between the two liquid phases on the surface of individual particles in each well. The organic eluate containing extracted analytes was evaporated and reconstituted for LC-MS/MS analysis. This fully automated LLE methodology avoids several disjointed steps involved in a manual or semiautomated LLE method, leading to significantly reduced sample preparation time, increased sample throughput, and clean sample extracts for improved ESI-MS/MS detection. The automated LLE methodology is universal and can be employed for sample preparation of other biological fluids. The complete bioanalytical method, based on the automated LLE and fast gradient LC-MS/MS, was validated and successfully applied to the quantitative analysis of protease inhibitors in rat plasma. PMID- 11217791 TI - Estimating the precision of exact mass measurements on an orthogonal time-of flight mass spectrometer. AB - The combination of orthogonal TOF/ESI MS exact mass measurement and on-line chromatography represents a powerful analytical tool for identifying unknown components in complex mixtures and is being widely utilized. The precision of these mass data is often incorrectly estimated as the precision or mean deviation obtained for reference standards under standard conditions. But, the precision of a mass measurement is dependent on the number of ions sampled in the measurement and, thus, is likely to be different for every measurement. A simple procedure for correctly estimating the precision of a specific mass measurement is presented, the limits of the procedure are investigated, and the utility and validity of the procedure are demonstrated. PMID- 11217792 TI - Tailored chemosensors for chloroaromatic acids using molecular imprinted TiO2 thin films on ion-sensitive field-effect transistors. AB - The SiO2 gate of an ion-sensitive field-effect transistor, (ISFET), is functionalized with a TiO2 film that includes imprinted molecular sites for 4 chlorophenoxy acetic acid, (1), or 2,4-dichlorophenoxy acetic acid, (2). The functionalized devices that include the imprinted interfaces reveal an impressive selectivity in the sensing of the imprinted substrates Na+ -1 or Na+ -2. The detection limit for Na+ -1 is (5+/-2) x 10(-4) M, which corresponds to 38 mV x dec(-1) in the concentration range of 0.5 to 6 mM. The detection limit for the analysis of Na+ -2 is (1.0+/-0.2) x 10(-5) M, which corresponds to 28 mV dec(-1) in the concentration range 0.1-9.0 mM. The equilibration time of the devices is ca. 5 min. PMID- 11217794 TI - The water project: a "real-world" experience for the quantitative analysis laboratory. PMID- 11217793 TI - Detecting DNA hybridization and damage. PMID- 11217795 TI - Tracing the history of selective ion sensors. PMID- 11217796 TI - Top-of-the-line MS. PMID- 11217797 TI - FR191512, a novel anti-influenza agent isolated from a fungus strain No.17415. I. Taxonomy, fermentation, isolation, physico-chemical properties and structure elucidation. AB - In the course of our screening for anti-influenza agents of microbial origin, FR191512 was isolated from the cultured broth of fungus strain No. 17415 as colorless powder. The structure of FR191512 was determined by several spectroscopic experiments as a novel polyphenolic compound. This compound showed potent antiviral activity against influenza A virus. PMID- 11217798 TI - FR191512, a novel anti-influenza agent isolated from a fungus strain No.17415. II. Biological properties. AB - FR191512, a novel polyphenolic compound, inhibited the infectivity of influenza A virus in Madin-Darby canine kidney (MDCK) cells in vitro. Furthermore, FR191512 showed good in vivo anti-influenza activity in a mouse model of intranasal infection with influenza A virus. The cytotoxic activity of FR191512 against MDCK cells was very weak. PMID- 11217799 TI - A potent seryl tRNA synthetase inhibitor SB-217452 isolated from a Streptomyces species. AB - A potent inhibitor of seryl tRNA synthetase, designated SB-217452 has been isolated from Streptomyces sp. ATCC 700974. The fermentation, isolation, structure elucidation and some properties are described. SB-217452 showed inhibitory activity against both Staphylococcus aureus and rat seryl tRNA synthetases, with similar IC50 values of approximately 8 nM. The inhibitor is the serine linked nucleoside moiety of the antibiotic albomycin delta2. In contrast to albomycin delta2, SB-217452 showed only very weak antibacterial activity against a limited range of microorganisms. The compound has not been previously reported as a naturally occurring metabolite. In addition to SB-217452, albomycin delta2 Fe3+ complex and the novel Al3+ complex were isolated from the fermentation. These complexes had no seryl tRNA synthetase inhibitory activity. PMID- 11217800 TI - Effects of nitrogen sources on cell growth and production of nystatin by Streptomyces noursei. AB - Cell growth and production of nystatin by Streptomyces noursei (ATCC 11455) were investigated on the three different nitrogen sources, ammonium sulphate, ammonium nitrate and sodium nitrate. S. noursei was able to utilise all of the three tested nitrogen sources for the growth and production of nystatin. High ammonium concentration had a negative effect on production of nystatin when phosphate and glucose was in excess. There was an increased production of nystatin when the cultures became ammonium limited. Cultivation with sodium nitrate as the nitrogen source resulted in a prolonged lag-phase for growth and about 50% lower final nystatin titres compared with cultures grown on nitrogen sources containing ammonium. Nystatin production was shown to be related to the specific growth rate, its production was increased at decreasing specific growth rates. PMID- 11217801 TI - Molecular cloning and sequencing of the edeine B1 amidinohydrolase gene of Bacillus brevis TT02-8 and its expression in Escherichia coli. AB - The gene encoding edeine B1 amidinohydrolase from Bacillus brevis TT02-8 was cloned into Escherichia coli and its nucleotide sequence was determined. An open reading frame was identified and was found to encode a polypeptide of 289 amino acid residues with a predicted molecular weight of 32,455, which was consistent with that previously calculated for edeine B1 amidinohydrolase purified from this bacterium. Comparison of the deduced amino acid sequence of this enzyme with other amidinohydrolases revealed the highest homology to B. subtilis agmatine ureohydolase. The enzymatic activity of the protein produced in Escherichia coli was analyzed. Three histidine residues, H-112, H-137 and H-151 in the edeine B1 amidinohydrolase, which are highly conserved in amidinohydrolases, were changed to alanine by site-directed mutagenesis. Analysis of each of these mutants revealed that three histidine residues are important but not essential for the enzyme activity. PMID- 11217802 TI - Studies on the biosynthesis of epothilones: the biosynthetic origin of the carbon skeleton. AB - The biosynthetic origin of the epothilone skeleton was studied by the incorporation of 13C and radioactively labeled precursors by Sorangium cellulosum So ce90. The carbon atoms are derived from acetate, propionate, the methyl group of S-adenosyl-methionine, and cysteine which also introduces the sulfur and nitrogen atoms. Epothilone biosynthesis starts with the formation of the thiazole part from acetate and cysteine. The incorporation of acetate or propionate units results in the formation of epothilones A and B, respectively. To introduce the epoxide function of epothilones A and B molecular oxygen is used. PMID- 11217803 TI - Blasticidin A derivatives with highly specific inhibitory activity toward aflatoxin production in Aspergillus parasiticus. AB - Blasticidin A (1), an antibiotic, has strong inhibitory activity toward aflatoxin production by Aspergillus parasiticus. We prepared some derivatives of 1 and examined their biological activities. Among them, derivatives 3 and 4 without the tetramic acid moiety of 1 maintained inhibitory activity toward aflatoxin production, but did not show antifungal activity or toxicity. RT-PCR experiments indicated that derivatives 3 and 4 as well as 1 significantly reduced the expression of genes encoding aflatoxin biosynthetic enzymes (pksA, ver-1 and omtA) and a regulatory gene (aflR) in A. parasiticus. These results suggested that derivatives 3 and 4 can inhibit aflatoxin production more specifically than 1 by inhibiting an early step prior to the expression of aflR in the pathway of aflatoxin biosynthesis. PMID- 11217804 TI - Synthesis of N-4909 analogs. Part I. A stimulant of apolipoprotein E secretion in human hepatoma G2 cells. AB - Analogs of N-4909 (1), which had a stimulating activity for apolipoprotein E (apo E) secretion in Human hepatoma Hep G2 cells, were prepared and their activities examined. Cyclic analogs which had different kinds of amino acids or different number of amino acids from N-4909 (1) showed less effect on apo E secretion from Hep G2 cells. The length of acyl chain was found to be an important factor for the activity. Shorter chain reduced the activity. Linear analogs were also prepared. One of their analogs, N-5849 (17), which had six amino acids was found to have strong activity. PMID- 11217805 TI - Novel triene-beta-lactone antibiotics, oxazolomycin derivative and its isomer, produced by Streptomyces sp. KSM-2690. PMID- 11217806 TI - Trichodion, a new bioactive pyrone from a Trichosporiella species. PMID- 11217807 TI - New pacidamycins produced by Streptomyces coeruleorubidus, NRRL 18370. PMID- 11217808 TI - Biosynthesis of IC202C, a new siderophore with immunosuppressive activity. PMID- 11217809 TI - Acetylation of aminoglycoside antibiotics with 6'-methylamino group, istamycin B and micronomicin, by a novel aminoglycoside 6'-acetyltransferase of actinomycete origin. PMID- 11217810 TI - Structures of fattiviracin family, antiviral antibiotics. PMID- 11217811 TI - Resistance to paromomycin is conferred by rpsL mutations, accompanied by an enhanced antibiotic production in Streptomyces coelicolor A3(2). PMID- 11217812 TI - Absence of cross-reactivity to myeloperoxidase of anti-thyroid microsomal antibodies in patients with autoimmune thyroid diseases. AB - BACKGROUND: Thyroperoxidase is the major antigen of the thyroid microsomal antibodies (TMA) detected in autoimmune thyroid diseases. Its amino acid sequence has 44% homology with myeloperoxidase (MPO), an enzyme present in the primary granules of neutrophils and one of the major antineutrophil cytoplasmic antibodies (ANCA) antigens. The objective of the present study was to investigate the presence of cross-reactivity to MPO of TMA. METHODS: We studied sera from 51 patients with autoimmune thyroid diseases, all of them TMA-positive. The presence of ANCA was investigated by indirect immunofluorescence and by capture enzyme linked immunosorbent assay. RESULTS: ANCA were positive in 3.9% of the TMA positive sera and none of them reacted with MPO. In contrast, the ANCA-positive sera revealed antielastase activity. None of the ANCA-positive cases presented clinical signs of vasculitis. However, these 2 patients had been on prolonged treatment with propylthiouracil. CONCLUSIONS: We conclude that there is no cross reactivity to MPO of TMA in patients with autoimmune thyroid diseases, possibly because of difference in the spatial configuration of the immunodominant region. The presence of ANCA in patients with autoimmune thyroid diseases without evidence of vasculitis might result from propyIthiouracil-induced polyclonal activation. PMID- 11217813 TI - Reversible sequestration of nitric oxide by hemoglobin during hemodialysis in end stage renal disease. AB - BACKGROUND: During hemodialysis, patients whose plasma concentrations of nitric oxide (NO) products increase reportedly experience hypotension. Therefore, whether NO bound to hemoglobin (Hb) could contribute to various clinical and laboratory changes during hemodialysis was explored in patients with end-stage renal disease (ESRD). METHODS: Ten patients were studied during 3 hemodialysis treatments with samples of blood analyzed for RBC nitrosyl Hb (HbNO), L-arginine, asymmetric dimethylarginine (ADMA), plasma nitrite+nitrate (NOx), and buffy coat NO synthase (NOS) activities. RESULTS: HbNO before and during hemodialysis varied considerably. Those with higher predialysis levels had lower HbNO values during dialysis, whereas HbNO levels in those with lower levels before dialysis increased. Plasma NOx did not correlate with HbNO, but change in HbNO in the first hour and change in NOx in the first 2 hours correlated with drop in diastolic and systolic blood pressures (BP), respectively. HbNO concentrations increased in patients with >35% drop in systolic BP, whereas in those with <35% drop, HbNO concentrations decreased. HbNO levels adjusted by the hematocrit showed a drop in HbNO for the <35% group and a >3-fold increase in the >35% group. HbNO levels were higher in men than in women, and levels and changes correlated with the hematocrit, skin temperatures, plasma ADMA, arginine, and buffy coat NOS. CONCLUSIONS: In patients with >35% drop in systolic BP, NO was scavenged by Hb in the circulating RBCs, undoubtedly attenuating the degree of hypotension. These data indicate that the amount of NO that is scavenged or released by Hb in the circulating RBCS during dialysis is highly variable and reversible. Various predialysis factors relate to the concentration of HbNO before and during dialysis, which in turn influence clinical findings that occur during the interdialytic period. PMID- 11217814 TI - Acute respiratory distress syndrome as a major clinical manifestation of thrombotic thrombocytopenic purpura. AB - BACKGROUND: Although the classical triad of thrombocytopenia, microangiopathic hemolytic anemia, and neurological changes has been well recognized, thrombotic thrombocytopenic purpura (TTP) sometimes presents with atypical clinical features. Some cases of acute respiratory distress syndrome (ARDS) were suspected to be a manifestation of TTP. METHODS: We examined retrospectively the medical records of patients with known TTP from 1981 to 1998. The patients who developed ARDS simultaneously with TTP were identified. Clinical, laboratory, and other pertinent data were reviewed; the clinical outcome was documented. RESULTS: Seven out of 56 patients with an established diagnosis of TTP were identified as having ARDS. All 7 patients had progressive dyspnea, persistent hypoxemia with diffuse pulmonary infiltrates, and no evidence of localized pneumonia, pulmonary emboli, congestive heart failure, or other identifiable lung diseases. In addition to ARDS, 4 patients developed progressive neurological (mental) changes, 3 developed fever, and 2 developed renal failure. Six patients were treated with ventilatory support in the ICU. Upon establishing the diagnosis of TTP, 6 patients were treated with exchange plasmapheresis (EP) and 1 patient with an infusion of fresh frozen plasma. Within 2 days of initiation of EP, 4 patients showed marked respiratory improvement; shortly thereafter, mechanical ventilation was ended. Complete and long-lasting remission was achieved in all 4 patients. Three patients died because of delayed diagnosis and untimely employment of EP. CONCLUSION: Life-threatening ARDS can be associated with TTP. It is recommended that all patients with ARDS and unexplained thrombocytopenia be evaluated for unrecognized TTP. Early recognition of ARDS associated with TTP and timely EP is critical to a favorable outcome. PMID- 11217815 TI - Poly-L-lysine-based molecular conjugate vectors: a high efficiency gene transfer system for human progenitor and leukemia cells. AB - BACKGROUND: Targeted, specific receptor mediated gene transfer is a major goal of gene therapy research to accomplish gene transfer exclusively to the desired cell population. METHODS: First, the use of natural receptor for stem cell factor and transferrin receptor-targeted gene transfer using poly-L-lysine-based molecular conjugate vectors was evaluated in a panel of hematopoietic progenitor cell lines. Second, the ability of poly-L-lysine to enhance adenovirus mediated gene transfer efficiency was examined in different cell lines by using recombinant adenovirus-poly-L-lysine molecular conjugate conglomerates (recMCVEGFP). RESULTS: Despite effective ligand internalization receptor, gene expression amplification in receptor positive cell lines was not uniformly observed. Therefore, using a poly-L-lysine-based, receptor-targeted vector, neither transferrin nor natural receptor for stem cell factor mediated gene transfer can be considered a universally applicable procedure that exclusively depends on the presence of receptors on the cell surface; rather, it is a cell specific phenomenon. In our model, poly-L-lysine is the major contributor for gene transfer to hematopoietic progenitor cells, mediating the initial vector-cell binding. Human progenitor cell lines are poorly transduceable with recombinant adenovirus vectors. This new poly-L-lysine-modified, adenovirus-based vector could overcome virus tropism restrictions and consistently achieve very high transduction efficiency (>90%) in cells otherwise refractory to adenovirus gene transfer. CONCLUSIONS: Polylysine based adenovirus vectors may have promise for situations in which high-efficiency gene transfer with transient high level transgene expression in hematopoietic cells is needed, such as leukemia vaccine protocols or for purging strategies in leukemia cell contaminated stem cell preparations. PMID- 11217816 TI - Adrenal insufficiency in HIV infection: a review and recommendations. AB - Adrenal insufficiency is known to be a complication of HIV infection, although estimates of its prevalence and severity vary. Adrenal insufficiency is the most serious endocrine complication that occurs in persons with HIV infection. Patients with acquired immune deficiency syndrome (AIDS) are considered to be at high risk for primary or secondary adrenal insufficiency. We describe 3 patients with AIDS who had clinical features suggestive of adrenal insufficiency, but their corticotropin (ACTH) stimulation tests were normal. Repeat testing confirmed the diagnosis in one patient, and further testing with the overnight metyrapone test revealed evidence of secondary adrenal insufficiency in the other patients. Persistent clinical improvement was evident on subsequent glucocorticoid therapy. A normal response to the ACTH stimulation test can be dangerously misleading. Patients with AIDS and suspected adrenal insufficiency who have normal screening by the ACTH stimulation test should undergo further testing for secondary adrenal disease. PMID- 11217817 TI - Prevention in liver disease. AB - Prevention has become an important component of medical therapy for a variety of diseases. Preventive strategies in liver disease are relatively underdeveloped and have focused mainly on specific complications of chronic liver disease and vaccination for viral hepatitis. Although public health initiatives designed to prevent certain forms of liver disease are in place, they seem to be underutilized and their utility has not been evaluated. The development of a comprehensive approach using public health initiatives in conjunction with strategies by health care providers is important because of the potential for decreasing the human and health care costs associated with hepatic dysfunction. This article reviews the available literature regarding prevention for health care providers, includes a summary of ongoing public health initiatives, and suggests an approach to prevention in liver disease. It is intended to raise awareness and encourage implementation of preventive strategies in hepatology. PMID- 11217818 TI - A case report of olanzapine-induced hypersensitivity syndrome. AB - Hypersensitivity syndrome is defined as a drug-induced complex of symptoms consisting of fever, rash, and internal organ involvement. The hypersensitivity syndrome is well recognized as being caused by anticonvulsants. Olanzapine is an atypical antipsychotic agent whose side effects include sedation, weight gain, and increased creatinine kinase and transaminase levels. To date, there have been no reports of hypersensitivity syndrome related to this drug. A 34-year-old man developed a severe generalized pruritic skin eruption, fever, eosinophilia, and toxic hepatitis 60 days after ingestion of olanzapine. After termination of olanzapine treatment, the fever resolved, the skin rash was reduced, eosinophil count was reduced to normal, and the transaminase levels were markedly reduced. Clinical features and the results of skin and liver biopsies indicated that the patient developed hypersensitivity syndrome caused by olanzapine. PMID- 11217819 TI - Severe symptomatic hyponatremia during citalopram therapy. AB - Hyponatremia secondary to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is an uncommon complication of treatment with the new class of antidepressant agents, the selective serotonin reuptake inhibitors (SSRIs). Most of the reported cases were associated with fluoxetine; only 2 have previously been described in association with citalopram. We describe an elderly woman who presented with severe symptomatic hyponatremia caused by the SIADH during therapy with citalopram. Because the use of SSRIs is becoming more popular among elderly depressed patients, the present case and the other 2 reported previously emphasize the need for greater awareness of the development of this serious and potentially fatal complication also in association with citalopram therapy and suggest that serum sodium levels should be monitored closely in elderly patients during treatment with citalopram. PMID- 11217820 TI - For the want of a test.. PMID- 11217822 TI - Science 'in crisis' says commission. PMID- 11217821 TI - Handling (mis?)appropriated data. PMID- 11217823 TI - Japan's ape sequencing effort set to unravel the brain's secrets. PMID- 11217824 TI - Japanese premier underlines opposition to human cloning. PMID- 11217826 TI - Germany targets international talent. PMID- 11217825 TI - Italian biologists left out in the cold. PMID- 11217827 TI - Greek plutonium haul raises smuggling fears. PMID- 11217829 TI - India struggles to cope with IT brain drain. PMID- 11217828 TI - Top research universities face up to gender bias. PMID- 11217830 TI - NASA celebrates as spacecraft homes in on asteroid. PMID- 11217831 TI - Australian leader pledges research boost before election. PMID- 11217832 TI - Tissue donations slump after revelations about misuse. PMID- 11217833 TI - Testing times for BSE. PMID- 11217834 TI - In search of a cure for CJD. PMID- 11217835 TI - Leaders need to realize that science can offer a route out of poverty. PMID- 11217836 TI - Secret behind Hungary's stellar intellects. PMID- 11217837 TI - Why didn't flood of print launch science in China? PMID- 11217838 TI - The harmonious hand. Marin Mersenne and the science of memorized music. PMID- 11217839 TI - Gained in the translation. PMID- 11217840 TI - The big picture. PMID- 11217841 TI - The dark side of aerosols. PMID- 11217843 TI - The age of the Universe. PMID- 11217842 TI - Diabetes. Dialogue between muscle and fat. PMID- 11217845 TI - The day the solar wind nearly died. PMID- 11217844 TI - Infectious speciation. PMID- 11217846 TI - Developmental biology. A macho way to make muscles. PMID- 11217847 TI - Dominant rams lose out by sperm depletion. PMID- 11217848 TI - Transgenic crops in natural habitats. PMID- 11217849 TI - Nanoscale control of chain polymerization. PMID- 11217850 TI - View of a mouse clock gene ticking. PMID- 11217852 TI - Measurement of stellar age from uranium decay. AB - The ages of the oldest stars in the Galaxy indicate when star formation began, and provide a minimum age for the Universe. Radioactive dating of meteoritic material and stars relies on comparing the present abundance ratios of radioactive and stable nuclear species to the theoretically predicted ratios of their production. The radioisotope 232Th (half-life 14 Gyr) has been used to date Galactic stars, but it decays by only a factor of two over the lifetime of the Universe. 238U (half-life 4.5 Gyr) is in principle a more precise age indicator, but even its strongest spectral line, from singly ionized uranium at a wavelength of 385.957 nm, has previously not been detected in stars. Here we report a measurement of this line in the very metal-poor star CS31082-001, a star which is strongly overabundant in its heavy elements. The derived uranium abundance, log(U/H) = -13.7 +/- 0.14 +/- 0.12 yields an age of 12.5 +/- 3 Gyr, though this is still model dependent. The observation of this cosmochronometer gives the most direct age determination of the Galaxy. Also, with improved theoretical and laboratory data, it will provide a highly precise lower limit to the age of the Universe. PMID- 11217853 TI - Generic mechanism for generating a liquid-liquid phase transition. AB - Recent experimental results indicate that phosphorus--a single-component system- can have a high-density liquid (HDL) and a low-density liquid (LDL) phase. A first-order transition between two liquids of different densities is consistent with experimental data for a variety of materials, including single-component systems such as water, silica and carbon. Molecular dynamics simulations of very specific models for supercooled water, liquid carbon and supercooled silica predict a LDL-HDL critical point, but a coherent and general interpretation of the LDL-HDL transition is lacking. Here we show that the presence of a LDL and a HDL can be directly related to an interaction potential with an attractive part and two characteristic short-range repulsive distances. This kind of interaction is common to other single-component materials in the liquid state (in particular, liquid metals), and such potentials are often used to describe systems that exhibit a density anomaly. However, our results show that the LDL and HDL phases can occur in systems with no density anomaly. Our results therefore present an experimental challenge to uncover a liquid-liquid transition in systems like liquid metals, regardless of the presence of a density anomaly. PMID- 11217851 TI - Functional annotation of a full-length mouse cDNA collection. AB - The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones. PMID- 11217854 TI - Strong radiative heating due to the mixing state of black carbon in atmospheric aerosols. AB - Aerosols affect the Earth's temperature and climate by altering the radiative properties of the atmosphere. A large positive component of this radiative forcing from aerosols is due to black carbon--soot--that is released from the burning of fossil fuel and biomass, and, to a lesser extent, natural fires, but the exact forcing is affected by how black carbon is mixed with other aerosol constituents. From studies of aerosol radiative forcing, it is known that black carbon can exist in one of several possible mixing states; distinct from other aerosol particles (externally mixed) or incorporated within them (internally mixed), or a black-carbon core could be surrounded by a well mixed shell. But so far it has been assumed that aerosols exist predominantly as an external mixture. Here I simulate the evolution of the chemical composition of aerosols, finding that the mixing state and direct forcing of the black-carbon component approach those of an internal mixture, largely due to coagulation and growth of aerosol particles. This finding implies a higher positive forcing from black carbon than previously thought, suggesting that the warming effect from black carbon may nearly balance the net cooling effect of other anthropogenic aerosol constituents. The magnitude of the direct radiative forcing from black carbon itself exceeds that due to CH4, suggesting that black carbon may be the second most important component of global warming after CO2 in terms of direct forcing. PMID- 11217855 TI - Tropical climate changes at millennial and orbital timescales on the Bolivian Altiplano. AB - Tropical South America is one of the three main centres of the global, zonal overturning circulation of the equatorial atmosphere (generally termed the 'Walker' circulation). Although this area plays a key role in global climate cycles, little is known about South American climate history. Here we describe sediment cores and down-hole logging results of deep drilling in the Salar de Uyuni, on the Bolivian Altiplano, located in the tropical Andes. We demonstrate that during the past 50,000 years the Altiplano underwent important changes in effective moisture at both orbital (20,000-year) and millennial timescales. Long duration wet periods, such as the Last Glacial Maximum--marked in the drill core by continuous deposition of lacustrine sediments--appear to have occurred in phase with summer insolation maxima produced by the Earth's precessional cycle. Short-duration, millennial events correlate well with North Atlantic cold events, including Heinrich events 1 and 2, as well as the Younger Dryas episode. At both millennial and orbital timescales, cold sea surface temperatures in the high latitude North Atlantic were coeval with wet conditions in tropical South America, suggesting a common forcing. PMID- 11217856 TI - Upper-mantle dynamics revealed by helium isotope variations along the southeast Indian ridge. AB - Helium isotope variations in igneous rocks are important for relating isotopic heterogeneity to convective mixing in the Earth's mantle. High 3He/4He ratios at many ocean islands, along with lower and relatively uniform values in mid-ocean ridge basalts (MORBs), are thought to result from a well mixed upper-mantle source for MORB and a distinct deeper-mantle source for ocean island basalts. At finer scales, 3He/4He variations along mid-ocean ridges have been related to underlying mantle heterogeneity, but relationships between the scales of geochemical segmentation and mantle convection remain enigmatic. Here we present helium isotope data for MORB glasses recovered along approximately 5,800 km of the southeast Indian ridge, and develop an approach to quantitatively relate spatial variations in geochemical and geophysical parameters at the Earth's surface. A point-to-point correlation analysis reveals structure in the helium isotope data at length scales of approximately 150 and approximately 400 km that appears to be related to secondary convection in the underlying mantle. PMID- 11217857 TI - Complete mitochondrial genome sequences of two extinct moas clarify ratite evolution. AB - The origin of the ratites, large flightless birds from the Southern Hemisphere, along with their flighted sister taxa, the South American tinamous, is central to understanding the role of plate tectonics in the distributions of modern birds and mammals. Defining the dates of ratite divergences is also critical for determining the age of modern avian orders. To resolve the ratite phylogeny and provide biogeographical data to examine these issues, we have here determined the first complete mitochondrial genome sequences of any extinct taxa--two New Zealand moa genera--along with a 1,000-base-pair sequence from an extinct Madagascan elephant-bird. For comparative data, we also generated 12 kilobases of contiguous sequence from the kiwi, cassowary, emu and two tinamou genera. This large dataset allows statistically precise estimates of molecular divergence dates and these support a Late Cretaceous vicariant speciation of ratite taxa, followed by the subsequent dispersal of the kiwi to New Zealand. This first molecular view of the break-up of Gondwana provides a new temporal framework for speciation events within other Gondwanan biota and can be used to evaluate competing biogeographical hypotheses. PMID- 11217858 TI - Wolbachia-induced incompatibility precedes other hybrid incompatibilities in Nasonia. AB - Wolbachia are cytoplasmically inherited bacteria that cause a number of reproductive alterations in insects, including cytoplasmic incompatibility, an incompatibility between sperm and egg that results in loss of sperm chromosomes following fertilization. Wolbachia are estimated to infect 15-20% of all insect species, and also are common in arachnids, isopods and nematodes. Therefore, Wolbachia-induced cytoplasmic incompatibility could be an important factor promoting rapid speciation in invertebrates, although this contention is controversial. Here we show that high levels of bidirectional cytoplasmic incompatibility between two closely related species of insects (the parasitic wasps Nasonia giraulti and Nasonia longicornis) preceded the evolution of other postmating reproductive barriers. The presence of Wolbachia severely reduces the frequency of hybrid offspring in interspecies crosses. However, antibiotic curing of the insects results in production of hybrids. Furthermore, F1 and F2 hybrids are completely viable and fertile, indicating the absence of F1 and F2 hybrid breakdown. Partial interspecific sexual isolation occurs, yet it is asymmetric and incomplete. Our results indicate that Wolbachia-induced reproductive isolation occurred in the early stages of speciation in this system, before the evolution of other postmating isolating mechanisms (for example, hybrid inviability and hybrid sterility). PMID- 11217859 TI - Evolutionary radiations and convergences in the structural organization of mammalian brains. AB - The sizes of mammalian brain components seem to be mostly related to the sizes of the whole brain (and body), suggesting a one-dimensional scale of encephalization. Previous multivariate study of such data concludes that evolutionary selection for enlargement of any one brain part is constrained to selection for a concerted enlargement of the whole brain. However, interactions between structurally related pairs of brain parts confirm reports of differential change in brain nuclei, and imply mosaic rather than concerted evolution. Here we analyse a large number of variables simultaneously using multi-dimensional methods. We show that the relative proportions of different systems of functionally integrated brain structures vary independently between different mammalian orders, demonstrating separate evolutionary radiations in mammalian brain organization. Within each major order we identify clusters of unrelated species that occupy similar behavioural niches and have convergently evolved similar brain proportions. We conclude that within orders, mosaic brain organization is caused by selective adaptation, whereas between orders it suggests an interplay between selection and constraints. PMID- 11217860 TI - Neurons derived from radial glial cells establish radial units in neocortex. AB - The neocortex of the adult brain consists of neurons and glia that are generated by precursor cells of the embryonic ventricular zone. In general, glia are generated after neurons during development, but radial glia are an exception to this rule. Radial glia are generated before neurogenesis and guide neuronal migration. Radial glia are mitotically active throughout neurogenesis, and disappear or become astrocytes when neuronal migration is complete. Although the lineage relationships of cortical neurons and glia have been explored, the clonal relationship of radial glia to other cortical cells remains unknown. It has been suggested that radial glia may be neuronal precursors, but this has not been demonstrated in vivo. We have used a retroviral vector encoding enhanced green fluorescent protein to label precursor cells in vivo and have examined clones 1-3 days later using morphological, immunohistochemical and electrophysiological techniques. Here we show that clones consist of mitotic radial glia and postmitotic neurons, and that neurons migrate along clonally related radial glia. Time-lapse images show that proliferative radial glia generate neurons. Our results support the concept that a lineage relationship between neurons and proliferative radial glia may underlie the radial organization of neocortex. PMID- 11217861 TI - The gating mechanism of the large mechanosensitive channel MscL. AB - The mechanosensitive channel of large conductance, MscL, is a ubiquitous membrane embedded valve involved in turgor regulation in bacteria. The crystal structure of MscL from Mycobacterium tuberculosis provides a starting point for analysing molecular mechanisms of tension-dependent channel gating. Here we develop structural models in which a cytoplasmic gate is formed by a bundle of five amino terminal helices (S1), previously unresolved in the crystal structure. When membrane tension is applied, the transmembrane barrel expands and pulls the gate apart through the S1-M1 linker. We tested these models by substituting cysteines for residues predicted to be near each other only in either the closed or open conformation. Our results demonstrate that S1 segments form the bundle when the channel is closed, and crosslinking between S1 segments prevents opening. S1 segments interact with M2 when the channel is open, and crosslinking of S1 to M2 impedes channel closing. Gating is affected by the length of the S1-M1 linker in a manner consistent with the model, revealing critical spatial relationships between the domains that transmit force from the lipid bilayer to the channel gate. PMID- 11217862 TI - macho-1 encodes a localized mRNA in ascidian eggs that specifies muscle fate during embryogenesis. AB - Maternal information stored in particular regions of the egg cytoplasm has an important function in the determination of developmental fate during early animal development. Ascidians show mosaic development; such autonomous development has been taken as evidence that prelocalized ooplasmic factors specify tissue precursor cells during embryogenesis. Interest has been concentrated on the mechanisms underlying the formation of muscle cells in the tail, as yellow coloured myoplasm in eggs is preferentially segregated into muscle-lineage blastomeres. Here we show that maternal messenger RNA of the macho-1 gene is a determinant of muscle fate in the ascidian Halocynthia roretzi. The macho-1 mRNA encodes a zinc-finger protein, and the mRNA is localized to the myoplasm of eggs. Depletion of the mRNA specifically resulted in the loss of primary muscle cells in the tail, as shown by the expression of muscle-specific molecular markers. The myoplasm of macho-1-deficient eggs lost its ability to promote muscle formation. Injection of synthesized macho-1 mRNA caused ectopic muscle formation in non muscle-lineage cells. Our results indicate that macho-1 maybe both required and sufficient for specification of muscle fate, and that the mRNA is a genuine, localized muscle determinant. PMID- 11217863 TI - Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. AB - The earliest defect in developing type 2 diabetes is insulin resistance, characterized by decreased glucose transport and metabolism in muscle and adipocytes. The glucose transporter GLUT4 mediates insulin-stimulated glucose uptake in adipocytes and muscle by rapidly moving from intracellular storage sites to the plasma membrane. In insulin-resistant states such as obesity and type 2 diabetes, GLUT4 expression is decreased in adipose tissue but preserved in muscle. Because skeletal muscle is the main site of insulin-stimulated glucose uptake, the role of adipose tissue GLUT4 downregulation in the pathogenesis of insulin resistance and diabetes is unclear. To determine the role of adipose GLUT4 in glucose homeostasis, we used Cre/loxP DNA recombination to generate mice with adipose-selective reduction of GLUT4 (G4A-/-). Here we show that these mice have normal growth and adipose mass despite markedly impaired insulin-stimulated glucose uptake in adipocytes. Although GLUT4 expression is preserved in muscle, these mice develop insulin resistance in muscle and liver, manifested by decreased biological responses and impaired activation of phosphoinositide-3-OH kinase. G4A-/- mice develop glucose intolerance and hyperinsulinaemia. Thus, downregulation of GLUT4 and glucose transport selectively in adipose tissue can cause insulin resistance and thereby increase the risk of developing diabetes. PMID- 11217864 TI - Negative regulation of T-cell activation and autoimmunity by Mgat5 N glycosylation. AB - T-cell activation requires clustering of a threshold number of T-cell receptors (TCRs) at the site of antigen presentation, a number that is reduced by CD28 co receptor recruitment of signalling proteins to TCRs. Here we demonstrate that a deficiency in beta1,6 N-acetylglucosaminyltransferase V (Mgat5), an enzyme in the N-glycosylation pathway, lowers T-cell activation thresholds by directly enhancing TCR clustering. Mgat5-deficient mice showed kidney autoimmune disease, enhanced delayed-type hypersensitivity, and increased susceptibility to experimental autoimmune encephalomyelitis. Recruitment of TCRs to agonist-coated beads, TCR signalling, actin microfilament re-organization, and agonist-induced proliferation were all enhanced in Mgat5-/- T cells. Mgat5 initiates GlcNAc beta1,6 branching on N-glycans, thereby increasing N-acetyllactosamine, the ligand for galectins, which are proteins known to modulate T-cell proliferation and apoptosis. Indeed, galectin-3 was associated with the TCR complex at the cell surface, an interaction dependent on Mgat5. Pre-treatment of wild-type T cells with lactose to compete for galectin binding produced a phenocopy of Mgat5-/- TCR clustering. These data indicate that a galectin-glycoprotein lattice strengthened by Mgat5-modified glycans restricts TCR recruitment to the site of antigen presentation. Dysregulation of Mgat5 in humans may increase susceptibility to autoimmune diseases, such as multiple sclerosis. PMID- 11217865 TI - Crystal structure of photosystem II from Synechococcus elongatus at 3.8 A resolution. AB - Oxygenic photosynthesis is the principal energy converter on earth. It is driven by photosystems I and II, two large protein-cofactor complexes located in the thylakoid membrane and acting in series. In photosystem II, water is oxidized; this event provides the overall process with the necessary electrons and protons, and the atmosphere with oxygen. To date, structural information on the architecture of the complex has been provided by electron microscopy of intact, active photosystem II at 15-30 A resolution, and by electron crystallography on two-dimensional crystals of D1-D2-CP47 photosystem II fragments without water oxidizing activity at 8 A resolution. Here we describe the X-ray structure of photosystem II on the basis of crystals fully active in water oxidation. The structure shows how protein subunits and cofactors are spatially organized. The larger subunits are assigned and the locations and orientations of the cofactors are defined. We also provide new information on the position, size and shape of the manganese cluster, which catalyzes water oxidation. PMID- 11217866 TI - Emergence of methicillin-resistant Staphylococcus aureus with intermediate glycopeptide resistance: clinical significance and treatment options. AB - Methicillin-resistant Staphylococcus aureus is a pathogen that is associated with serious infections that pose a significant risk of morbidity and mortality because of their multidrug resistant nature. Until recently, therapeutic options were limited to vancomycin, making the use of this drug widespread. Unfortunately, the continued application of this drug has led to the emergence of glycopeptide intermediate susceptible S. aureus (GISA). By definition, these organisms demonstrated a vancomycin minimum inhibitory concentration (MIC) of >4 mg/L and <32 mg/L. However, although the mechanism of resistance is not fully elucidated at this time, GISA strains have demonstrated thickened or aggregated cell walls, an increase in penicillin binding proteins and greater autolytic activity. At present, the overall number of reported cases of GISA is relatively low. In most cases, thus far, prolonged courses of vancomycin were reported. A few cases reported monitoring serum vancomycin concentrations but because of limited information, no association with outcome can be made. Whether these GISA strains will become more widespread or evolve into fully glycopeptide resistant strains is unknown at this time. Although there are a number of new agents that possess activity against these pathogens, there is no consensus regarding specific recommendations for treatment. Strict infection control practices, routine screening for resistance and controlled use of antibacterial agents, especially vancomycin, are critical steps in preventing the further development of resistance among staphylococci. PMID- 11217868 TI - The emerging roles of non-nucleoside reverse transcriptase inhibitors in antiretroviral therapy. AB - The availability of potent non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimens for antiretroviral therapy and concerns regarding protease inhibitor (PI)-related metabolic disturbances have led to significant shifts in treatment practices in HIV infection. NNRTI-based regimens may have several advantages over PI-based therapy for initial or prolonged therapy, including more convenient administration regimens, lower tablet volume, fewer drug interactions, and central nervous system penetration. No data from prospective clinical trials currently exist comparing the 3 approved agents (efavirenz, nevirapine or delavirdine). Both efavirenz and nevirapine have been compared to triple therapy with the PI indinavir over 48 weeks as initial therapy, with similar responses being observed with nevirapine regimens and superiority observed with efavirenz. A smaller 24-week study has suggested nevirapine may be superior to the PI nelfinavir. Limited comparative data in patients with high viral loads treated with nevirapine- or delavirdine-based regimens currently exist. However, cohort data and selected patient data from clinical trials suggest comparable activity to PI-based regimens in these patients. The superiority of efavirenz over indinavir-based regimens has been observed in comparative data in a subset of patients with high viral loads. In treatment-experienced patients, available uncontrolled data suggest these agents contribute to regimen efficacy in NNRTI naive, treatment-experienced patients. Efavirenz has demonstrated superiority over nelfinavir in nucleoside-experienced patients, although combining these 2 agents may represent the best approach in these circumstances. The tolerability of NNRTIs appears generally good with few individuals discontinuing in clinical studies as a result of adverse drug events. The majority of adverse events with NNRTIs occur within the first month, and are predictable and manageable without therapy interruption. PMID- 11217869 TI - Response to inhaled nitric oxide in premature and term neonates. AB - Inhaled nitric oxide (iNO) has emerged as a promising therapeutic agent in the treatment of persistent pulmonary hypertension of the newborn. Several theories exist regarding causes of both response and nonresponse to iNO. Clinical trials differentiate disease entities (primary vs secondary persistent pulmonary hypertension associated with meconium aspiration syndrome, pneumonia or congenital diaphragmatic hernia) and their specific response rates. iNO combined with high-frequency ventilation appears to be superior to inhalation of nitric oxide (NO) during conventional ventilation. Little is known regarding the role of the degree of lung expansion and its modification -- no matter what mode of ventilation is applied. Gestational age plays an important role in relation to the potential adverse effects of NO. Of particular concern in the premature neonate is the effect of NO on bleeding time and the inhibition of platelet aggregation. Those potentially hazardous effects need to be carefully weighed against early intervention with iNO at a comparably low oxygenation index in order to prevent the vicious cycle of hypoxaemia and subsequent increased right to-left shunting. Further studies are required to determine the optimal timing, mode of delivery and mode of ventilation used with iNO therapy in order to optimise the response of premature and term neonates. PMID- 11217867 TI - Olanzapine: an updated review of its use in the management of schizophrenia. AB - Olanzapine, a thienobenzodiazepine derivative, is a second generation (atypical) antipsychotic agent which has proven efficacy against the positive and negative symptoms of schizophrenia. Compared with conventional antipsychotics, it has greater affinity for serotonin 5-HT2A than for dopamine D2 receptors. In large, well controlled trials in patients with schizophrenia or related psychoses, olanzapine 5 to 20 mg/day was significantly superior to haloperidol 5 to 20 mg/day in overall improvements in psychopathology rating scales and in the treatment of depressive and negative symptoms, and was comparable in effects on positive psychotic symptoms. The 1-year risk of relapse (rehospitalisation) was significantly lower with olanzapine than with haloperidol treatment. In the first double-blind comparative study (28-week) of olanzapine and risperidone, olanzapine 10 to 20 mg/day proved to be significantly more effective than risperidone 4 to 12 mg/day in the treatment of negative and depressive symptoms but not on overall psychopathology symptoms. In contrast, preliminary results from an 8-week controlled study suggested risperidone 2 to 6 mg/day was superior to olanzapine 5 to 20 mg/day against positive and anxiety/depressive symptoms (p < 0.05), although consistent with the first study, both agents demonstrated similar efficacy on measures of overall psychopathology. Improvements in general cognitive function seen with olanzapine treatment in a 1-year controlled study of patients with early-phase schizophrenia, were significantly greater than changes seen with either risperidone or haloperidol. However, preliminary results from an 8-week trial showed comparable cognitive enhancing effects of olanzapine and risperidone treatment in patients with schizophrenia or schizoaffective disorder. Several studies indicate that olanzapine has benefits against symptoms of aggression and agitation, while other studies strongly support the effectiveness of olanzapine in the treatment of depressive symptomatology. Olanzapine is associated with significantly fewer extrapyramidal symptoms than haloperidol and risperidone. In addition, olanzapine is not associated with a risk of agranulocytosis as seen with clozapine or clinically significant hyperprolactinaemia as seen with risperidone or prolongation of the QT interval. The most common adverse effects reported with olanzapine are bodyweight gain, somnolence, dizziness, anticholinergic effects (constipation and dry mouth) and transient asymptomatic liver enzyme elevations. In comparison with haloperidol, the adverse events reported significantly more frequently with olanzapine in > or = 3.5% of patients were dry mouth, bodyweight gain and increased appetite and compared with risperidone, only bodyweight gain occurred significantly more frequently with olanzapine. The high acquisition cost of olanzapine is offset by reductions in other treatment costs (inpatient and/or outpatient services) of schizophrenia. Pharmacoeconomic analyses indicate that olanzapine does not significantly increase, and may even decrease, the overall direct treatment costs of schizophrenia, compared with haloperidol. Compared with risperidone, olanzapine has also been reported to decrease overall treatment costs, despite the several-fold higher daily acquisition cost of the drug. Olanzapine treatment improves quality of life in patients with schizophrenia and related psychoses to a greater extent than haloperidol, and to broadly the same extent as risperidone. CONCLUSIONS: Olanzapine demonstrated superior antipsychotic efficacy compared with haloperidol in the treatment of acute phase schizophrenia, and in the treatment of some patients with first-episode or treatment-resistant schizophrenia. The reduced risk of adverse events and therapeutic superiority compared with haloperidol and risperidone in the treatment of negative and depressive symptoms support the choice of olanzapine as a first-line option in the management of schizophrenia in the acute phase and for the maintenance of treatment response. PMID- 11217870 TI - Cholinesterase inhibitors for Alzheimer's disease. AB - Alzheimer's disease (AD) is the most common age-related neurodegenerative disease and has become an urgent public health problem in most areas of the world. Substantial progress has been made in understanding the basic neurobiology of AD and, as a result, new drugs for its treatment have become available. Cholinesterase inhibitors (ChEIs), which increase the availability of acetylcholine in central synapses, have become the main approach to symptomatic treatment. ChEIs that have been approved or submitted to the US Food and Drug Administration (FDA) include tacrine, donepezil, metrifonate, rivastigmine and galantamine. In this review we discuss their pharmacology, clinical experience to date with their use and their potential benefits or disadvantages. ChEIs have a significant, although modest, effect on the cognitive status of patients with AD. In addition to their effect on cognition, ChEIs have a positive effect on mood and behaviour. Uncertainty remains about the duration of the benefit because few studies of these compounds beyond one year have been published. Although ChEIs are generally well tolerated, all patients should be followed closely for possible adverse effects. There is no substantial difference in the effectivenes of the various ChEIs, however, they may have different safety profiles. We believe the benefits of their use outweigh the risks and costs and, therefore, ChEls should be considered as primary therapy for patients with mild to moderate AD. PMID- 11217871 TI - Treatments for androgenetic alopecia and alopecia areata: current options and future prospects. AB - Androgenetic alopecia and alopecia areata are common disorders of the hair follicle which may heavily influence self esteem and self image. Androgenetic alopecia is caused by the heightened sensitivity of scalp follicles to dihydro- testosterone whereas alopecia areata is induced by an autoimmune reaction. Current drug treatment approaches include the use of regrowth stimulators such as topical minoxidil and oral finasteride for androgenetic alopecia, as well as topical minoxidil, dithranol (anthralin), corticosteroids, contact sensitisers, and psoralen plus ultraviolet A irradiation (PUVA) therapy for alopecia areata. Combination regimens are also proposed. However, extreme cases of either type of alopecia do not generally respond well to these existing treatments. For this reason, new therapeutic strategies are directed towards both improving the targeting of existing agents, as well as the development of novel hypertrichotic modalities. PMID- 11217872 TI - Inhaled budesonide/formoterol combination. AB - Current evidence suggests that the addition of the long acting inhaled beta2 agonist formoterol to low or moderate doses of the inhaled corticosteroid budesonide is effective in improving lung function and reducing the incidence of asthma exacerbations. Concurrent use of budesonide with formoterol does not result in any untoward interaction that affects the pharmacodynamic or pharmacokinetic profiles of the individual drugs, or their adverse effect profiles. The administration of combined budesonide/formoterol is effective in improving morning and evening peak expiratory flow rates in adults with persistent asthma. Control of asthma symptoms is also significantly improved. In children aged 4 to 17 years, combined budesonide/formoterol is effective in increasing both morning and evening peak expiratory flow rates and significantly improving forced expiratory volume in 1 second (FEV1). The most commonly encountered adverse effects in clinical trials with combination budesonide/formoterol therapy have been respiratory infection, pharyngitis and coughing. No adverse effects on pulse rate, blood pressure or serum potassium have been reported with combination therapy. PMID- 11217873 TI - Fluoxetine: a review of its therapeutic potential in the treatment of depression associated with physical illness. AB - Fluoxetine is a potent and selective inhibitor of neuronal serotonin (5 hydroxytryptamine) reuptake. Fluoxetine reduces food, energy and carbohydrate intake and increases resting energy expenditure, which may account for the moderate and transient bodyweight loss observed with its use. Glucose tolerance and/or hypoglycaemia in patients with type 2 diabetes mellitus improve with fluoxetine therapy. The ability of fluoxetine to inhibit cytochrome P450 (CYP) isoenzymes (CYP2D6, CYP2C and CYP3A4), is potentially important for patients with physical illness who may be taking multiple concomitant medications. Fluoxetine was more effective than placebo in 2 double-blind, randomised trials, and according to limited data appears to be equally effective compared with other SSRIs and tricyclic antidepressants (TCAs), in the treatment of depression in patients with HIV/AIDS. The efficacy of fluoxetine is also superior to that of placebo in the treatment of depression in patients with diabetes mellitus and stroke as shown in double-blind randomised trials, although its efficacy relative to that of nortriptyline in stroke is uncertain. Fluoxetine had similar efficacy to that of desipramine in patients with cancer, with improved Hamilton Depression Rating Scale and quality-of-life scores from baseline; however, the drug was not more effective than placebo in a double-blind randomised trial. Medically healthy individuals tolerate fluoxetine well. Like other SSRIs, fluoxetine lacks the anticholinergic, cardiovascular, sedative and weight-increasing properties of TCAs, and is safer in overdose than TCAs and monoamine oxidase inhibitors. Rates of sexual dysfunction and suicidal ideation with fluoxetine appear similar to those seen with other SSRIs. CONCLUSION: Fluoxetine has shown superior efficacy compared with placebo in the treatment of depression in patients with HIV/AIDS, diabetes mellitus or stroke; however, it has not significantly improved depressive symptoms versus placebo in patients with cancer. The efficacy of fluoxetine appears similar to that of desipramine in patients with stroke, cancer or HIV, and is similar to that of sertraline or paroxetine in patients with HIV/AIDS; comparisons with nortriptyline give equivocal results. The potential for drug interactions with fluoxetine use should be carefully considered because most patients with comorbid physical illness will be receiving multiple comedications. Although fluoxetine has proved effective as an antidepressant in this population in several clinical trials, its drug interaction profile and long half-life are a potential limitation, and these properties should be carefully considered in relation to the status of each patient. PMID- 11217874 TI - The role of fluoroquinolones in tuberculosis today. AB - Tuberculosis is a growing international health concern; it is the leading infectious cause of death in the world today. The fluoroquinolones are the most recent class of drugs offering hope in the fight against this disease. Ciprofloxacin, ofloxacin, levofloxacin and sparfloxacin are currently the most commonly used agents used against Mycobacterium tuberculosis (TB), with in vitro minimum inhibitory concentrations (MICs) of 0.1 to 4 mcg/ml. Resistance in TB to fluoroquinolones may occur spontaneously or may be acquired, especially when these agents are used inappropriately. Cross-resistance among the fluoroquinolones has been shown in TB. The fluoroquinolones offer a favourable pharmacokinetic profile for the treatment of TB. Most demonstrate excellent oral bioavailability and achieve maximum (peak) serum concentrations well above the MIC. They are also distributed widely, including intracellularly. The fluoroquinolones are cleared renally and/or hepatically, with varying serum half lives. Fluoroquinolones are most effective when the peak concentration (Cmax) to MIC ratio is maximised. Fluoroquinolones such as ciprofloxacin and ofloxacin have been used in regimens for the prevention of TB, but have been poorly tolerated when used in combination with pyrazinamide. Favourable responses with fluoroquinolones in regimens used in the treatment of clinical TB disease have been seen. They, however, are not to be considered as equal replacements for isoniazid or rifampicin (rifampin) and should be used with at least 2 other antituberculous agents. Therapeutic drug monitoring of fluoroquinolones is beneficial in assuring that maximum Cmax to MIC ratios are being achieved, especially in patients at risk for malabsorption, such as those infected with HIV. Higher, once-daily doses of most fluoroquinolones are becoming more common in treating TB. Fluoroquinolones are generally well tolerated with long term use in treating TB, but rare, serious adverse effects have been reported with general fluoroquinolone use. The most common drug interactions with fluoroquinolones in TB therapy include the malabsorption interactions associated with multivalent cations and cytochrome P450 interactions with ciprofloxacin. An increased risk of central nervous system effects with concomitant cycloserine has been reported and seen clinically. When using fluoroquinolones to treat TB, careful consideration of individual susceptibility patterns, pharmacokinetic and toxicity profiles should be taken. The aid of a TB expert may also be warranted. The exact role of the fluoroquinolones in treating TB remains to be determined. PMID- 11217875 TI - Iterative optimal design of PET experiments for estimating beta-adrenergic receptor concentration. AB - To estimate in vivo myocardial beta-adrenergic receptor concentration with sufficient precision and to reduce the experimental complexities in positron emission tomography (PET), an iterative optimal design method is applied. An initial three-injection protocol, utilising [F-18]-labelled (R)- and (S) fluorocarazolol and unlabelled (S)-fluorocarazolol, is optimised for ligand dosages and administration times to maximise the precision of all model parameters using the D-optimal criterion. Using this experimental protocol, PET data are collected in porcine studies, and model parameters are estimated. All model parameters are identified with satisfactory precision. The in vivo myocardial beta-receptor concentration is 7.5+/-0.6 pmol x ml(-1), which corresponds to the in vitro result of 10.1+/-1.3 pmol x ml(-1). With more accurate parameter values, a simplified two-injection protocol is optimally designed, utilising only radiolabelled and unlabelled (S)-fluorocarazolol, based on a new criterion to maximise the precision of the beta-receptor concentration. This revised optimum design predicts that the in vivo beta-receptor concentration can be estimated with good precision but reduced experiment complexity. PMID- 11217876 TI - Measurement of femoral neck anteversion in 3D. Part 1: 3D imaging method. AB - Femoral neck anteversion is the torsion of the femoral head with reference to the distal femur. Conventional methods that use cross-sectional computed tomography (CT), magnetic resonance or ultrasound images to estimate femoral anteversion have met with several problems owing to the complex, three-dimensional (3D) structure of the femur. These problems include not only the difficulty of defining the direction of the femoral neck axis and condylar line but also the dependency upon patient positioning. In particular, the femoral neck axis, the direction of the femoral head, known as the major source of error, is difficult to determine from either a single or several two-dimensional (2D) cross-sectional images. A new method has been devised for the measurement of femoral anteversion using the 3D imaging technique. 3D reconstructed CT images from the femoral head and trochanter to the distal femur are used to measure the anteversion. It is necessary to remove the soft tissue from the CT images and extract just the bone part. Then, the femoral anteversion is measured from a computer-rendered femur image. The 3D imaging method is compared with both the conventional 2D method and the physical method using 20 dried femurs. For the physical method, which is used as a reference value, a special apparatus is devised. The average difference between the results of the physical method and those of the 2D CT method is 5.33 degrees. The average difference between the results of the physical method and those of the 3D imaging method is 0.45 degrees. Seventy-four patients, who suffer from toe-in-gait disease, are tested to compare the 3D imaging method with the conventional 2D CT method. The average difference between the 2D and 3D methods is 8.6 degrees, and the standard is 7.43 degrees. This method provides a very accurate and reliable measurement of femoral anteversion, as it is virtually equivalent to the direct measurement of bisected dried femur in vitro. PMID- 11217877 TI - Measurement of femoral neck anteversion in 3D. Part 2: 3D modelling method. AB - Femoral neck anteversion is the torsion of the femoral head with reference to the distal femur. Conventional methods that use cross-sectional computed tomography (CT), magnetic resonance or ultrasound images to estimate femoral anteversion have met with several problems owing to the complex three-dimensional (3D) structure of the femur. A 3D imaging method has been developed that virtually measures femoral anteversion on the 3D computer space with continuous CT slices; this 3D method provides more accurate and reliable results than conventional 2D CT measurements. A 3D modelling method is devised for the measurement of femoral neck anteversion. This method has advantages over the 3D imaging method, such as shorter processing time, reduced number of slices and an objective result compared with the 3D imaging method. The results of the 3D modelling method are compared with the conventional CT methods (2D CT method and 3D imaging method) using 20 dried femurs. PMID- 11217878 TI - Analysis of postural sway using entropy measures of signal complexity. AB - A stochastic complexity analysis is applied to centre-of-pressure (COP) time series, by using different complexity features, namely the spectral entropy, the approximate entropy, and the singular value decomposition spectrum entropy. A principal component analysis allows an estimate of the overall signal complexity in terms of the ensemble complexity score; the difference in values between open eyes (OE) and closed-eyes (CE) trials is used for clustering purposes. In experiments on healthy young adults, the complexity of the mediolateral component is shown not to depend on the manipulation of vision. Conversely, the increase of the anteroposterior complexity in OE conditions can be statistically significant, leading to a functional division of the subjects into two groups: the Romberg ratios (RRs), namely the ratios of the CE measure to the OE measure, are: RR = 1.19 +/- 0.15 (group 1 subjects), and RR = 1.05 +/- 0.14 (group 2 subjects). Multivariate statistical techniques are applied to the complexity features and the parameters of a postural sway model recently proposed; the results suggest that the complexity change is the sign of information-generating behaviours of postural fluctuations, in the presence of a control strategy which aims at loosening long-range correlation and decreasing stochastic activity when visual feedback is allowed. PMID- 11217879 TI - A method for turbulent noise estimation in voiced signals. AB - In this article a new acoustic parameter is introduced and it is shown that it may serve as an indicator of laryngeal function. It is termed the turbulent noise index (TNI) and is defined as 100(1 - Rmax), where Rmax is the mean value of the maximum correlation coefficient between each pair of consecutive glottal cycles in the voiced signal. A method for its calculation is described. Experiments with synthetic and natural voice signals show that TNI is almost independent of frequency modulation noise and amplitude modulation noise. TNI is compared with HNR (harmonic-to-noise ratio) and NNE (normalised noise energy) which require high stationarity of the voice signal and are substantially affected by slow changes of frequency and amplitude. When the parameters HNR and NNE are used to discriminate between normal and pathological voices, the overlap area contains 21.5% and 23.5% of the total number of pathological voices, respectively. Using TNI, the normal and pathological voices overlap is 14.8% of the total number of pathological voices, i.e. compared to the other noise parameters TNI has a significant advantage as a diagnostic parameter. PMID- 11217880 TI - Analysis and decomposition of signals obtained by thigh-fixed uni-axial accelerometry during normal walking. AB - The use of piezo-resistive uni-axial accelerometer signals in gait analysis is complicated by the fact that the measured signal is composed of different types of acceleration. The aim of the study is to obtain insight into the signal from a tangential accelerometer attached to the thigh during walking. Six subjects walk with three different speeds. Simultaneous measurements are performed with accelerometers, footswitches and an opto-electronic system. The components of the accelerometer signal are calculated from the opto-electronic system. A clear relationship is found between the measured and calculated accelerometer signals (range RMS: 0.76-3.69 m x s(-2), range rms: 0.22-0.61). The most pronounced feature is a high positive acceleration peak (> 10 m x s(-2)) at the end of the cycle. The gravitational acceleration during one cycle is characterised by a sinusoidal shape, whereas the inertial acceleration contains higher-frequency components (up to 20 Hz). During the major part of the gait cycle, the gravitational and inertial acceleration make opposing contributions to the signal As a result, the gravitational acceleration influences the amplitudes of the measured acceleration signal, the shape and peaks of which are mainly determined by the inertial acceleration. Because the gravitational and inertial accelerations differ in frequency components, the application for gait analysis remains feasible. PMID- 11217882 TI - Adaptive wavelet filtering for analysis of event-related potentials from the electro-encephalogram. AB - A challenging task in psychophysiology is the extraction of event-related potentials (ERPs) from the background electro-encephalogram. The task is made more difficult by the properties of ERPs, which typically consist of multiple features of variable latency, localised in time and frequency. A novel technique is described for analysis of ERPs, adaptive wavelet filtering (AWF), which is proposed as an alternative to trial averaging. Band-limited detail representations of each trial are obtained using wavelet analysis. The Woody adaptive filter is then used to align trials with respect to the evoked response. In a simulation study, the AWF extracts 39% of higher-frequency signal variance from background noise, compared with less than 1% for standard averaging and the Woody filter. The AWF is applied to a data-set of 448 ERPs, comprising right finger button presses from eight subjects. Average split-half reliability of the AWF on scales up to 12 Hz was 0.51. PMID- 11217881 TI - Three-dimensional mapping of brainstem functional lesions. AB - The human brainstem is a highly complex structure where even small lesions can give rise to a variety of symptoms and outward signs. Localising the area of dysfunction within the brainstem is often a difficult task. To make localisation easier, a neural net system has been developed which uses 72 clinical and neurophysiological data inputs to provide a display (using 5268 voxels) on a three-dimensional model of the human brainstem. The net was trained by means of a back-propagation algorithm, over a pool of 580 example cases. Assessed on 200 test cases, the net correctly localised 83.6% of the target voxels; furthermore the net correctly localised the lesions in 31 out of 37 patients. Because this computer-assisted method provides reliable and quantitative localisation of brainstem areas of dysfunction and can be used as a 3D interactive functional atlas, it is expected to prove useful as a diagnostic tool for assessing focal brainstem lesions. PMID- 11217883 TI - Isopower mapping of electrogastrograms in short-bowel syndrome. AB - Methods for making topographic or isopower electrogastrographic (EGG) maps and for obtaining maximum power foci (MPFs) by means of 27-channel EGG recordings are briefly described. The methods are applied to short-bowel syndrome (SBS). The gastro-intestinal tract is traced by videofluorograms after X-ray-opaque barium has been ingested. The MPFs are generally located on the trace of the gastro intestinal tract. The gastric area is occupied by 3 cycles x min(-1) (up to 28% of total MPFs) and 6 cycles x min(-1) MPFs (26%). The trace of the small intestine is occupied mainly by 8 cycles x min(-1) (39%) and 10 cycles x min(-1) (43%) MPFs. The trace of the colon is occupied almost evenly by all five spectral frequency groups, that is, by 1 (58%), 3 (53%), 6 (48%), 8 (57%) and 10 cycles x min(-1) (42%). Most interestingly, the numbers of 8-10 cycles x min(-1) power foci found on EGG maps (including MPFs and relatively higher power foci) are proportional to the remaining length at operation and to the length of the remaining small intestine in the long-term, over 6 years postoperatively. It is therefore possible to follow approximately the trace of the gastero-intestinal tract. PMID- 11217884 TI - Identification of post-myocardial infarction patients with ventricular tachycardia by time-domain intra-QRS analysis of signal-averaged electrocardiogram and magnetocardiogram. AB - A new time-domain analysis method, which quantifies ECG/MCG intra-QRS fragmentation, is applied to parts of the QRS complex to identify post-myocardial infarction patients with ventricular tachycardia. Three leads of signal-averaged electrocardiograms and nine leads of magnetocardiograms were band-pass filtered (74 Hz to 180 Hz). The filtered signals showed fragmentation in the QRS region, which was quantified by the number of peaks M and a score S, that is the product of M and the sum of the peak amplitudes. Both parameters were determined for the first 80 ms of the QRS complex and the total QRS complex in each channel. For classification, the mean-values of the parameters M and S of the three electrical leads and the nine magnetic leads were calculated. Late potential and late field analyses were performed for the same signals. 31 myocardial infarction patients were included, 20 of them with a history of documented ventricular tachycardia (VT). Identification of VT patients using the SAECG led to better results (sensitivity 95%, specificity 91%) considering the entire QRS complex than with the standard late potential analysis suggested by Simson (sensitivity 90%, specificity 73%). For the SAMCG and the entire QRS complex results using the parameters S and M are also better (sensitivity 95%, specificity 100%) than for the late field analysis (sensitivity 90% and specificity 100%). For the first 80 ms, the performance of the parameters M and S is only slightly decreased. PMID- 11217885 TI - Risk evaluation of ventricular tachycardia using wavelet transform irregularity of the high-resolution electrocardiogram. AB - A new method for analysis of high-resolution ECG signals using a wavelet transform based on a modified Morlet function is presented. A polynomial filter is used to reduce low-frequency, high-amplitude noise components in the analysed signals. The method is tested on test ECG signals with simulated late potentials and finally verified on two post-infarction patient (PP) groups: 62 PPs with ventricular tachycardia and 44 PPs without arrhythmia. A new quantitative parameter, the irregularity factor, is proposed for discrimination between the study groups. The results show a significant difference in the parameter values for tachycardia patients compared with those for patients without arrhythmia. The sensitivity of the proposed method is 85%, and the specificity is 93%. PMID- 11217887 TI - Evaluation of renormalised entropy for risk stratification using heart rate variability data. AB - Standard time and frequency parameters of heart rate variability (HRV) describe only linear and periodic behaviour, whereas more complex relationships cannot be recognised. A method that may be capable of assessing more complex properties is the non-linear measure of 'renormalised entropy.' A new concept of the method, RE(AR), has been developed, based on a non-linear renormalisation of autoregressive spectral distributions. To test the hypothesis that renormalised entropy may improve the result of high-risk stratification after myocardial infarction, it is applied to a clinical pilot study (41 subjects) and to prospective data of the St George's Hospital post-infarction database (572 patients). The study shows that the new RE(AR) method is more reproducible and more stable in time than a previously introduced method (p<0.001). Moreover, the results of the study confirm the hypothesis that on average, the survivors have negative values of RE(AR) (-0.11+/-0.18), whereas the non-survivors have positive values (0.03+/-0.22, p<0.01). Further, the study shows that the combination of an HRV triangular index and RE(AR) leads to a better prediction of sudden arrhythmic death than standard measurements of HRV. In summary, the new RE(AR) method is an independent measure in HRV analysis that may be suitable for risk stratification in patients after myocardial infarction. PMID- 11217888 TI - Preparation of a pure autologous biodegradable fibrin matrix for tissue engineering. AB - Parallel to the growing role of tissue engineering, the need for cell embedding materials, which allow cells to stabilise in a three-dimensional distribution, has increased. Although several substances have been tested, fibrin is thus far the only one that permits the clinical application of cultured tissue. To date, autologous fibrinogen has usually been polymerised with bovine thrombin, which can cause severe immunological side effects. The objective of this study was to explore the practicability of obtaining autologous thrombin from a single patient in an adequate concentration and amount. Fibrinogen was cryoprecipitated from 200 ml of freshly-frozen plasma. Thrombin was isolated from the supernatant through ion-exchange chromatography. The thrombin was first bound to Sephadex A-50 and then eluated using 2 ml of a salt buffer (2.0 M NaCl in 0.015 M trisodiumcitrate, pH 7.0). The activity of the thrombin (51 NIH x ml(-1) to 414 NIH x ml(-1) reached levels comparable to those in commercially available fibrin glues (4-500 NIH x ml(-1)). The study has shown that it is possible to obtain a sufficient amount of autologous thrombin from a single donor to create a fibrin matrix of high efficiency without the risk of immunological and infectious side effects. PMID- 11217889 TI - New model to characterise cell-substrate adhesion in the presence of osmosis. AB - A simple model of cell-substrate adhesion, in response to osmosis change, is derived to describe quantitatively the interrelationships between osmotic inflation, contact area and angle, membrane stretching and adhesion strength. As the cell inflates, the contact area shrinks in dimension, until the cell is eventually lifted off the substrate. The theoretical prediction is consistent with other published data. PMID- 11217886 TI - Increase in pulse transit time to the foot after epidural anaesthesia treatment. AB - Epidurally induced anaesthetic treatment is a routine treatment for pain relief during surgical procedure, based on blocking the sensory and sympathetic fibres that mediate pain. The epidural sympathetic block results in relaxation of the muscle walls in the lower limbs, which can be assessed by the resultant haemodynamic changes. In the current study, the difference tt,f in the transit time of the blood pressure pulses between the toe and the finger is measured by photoplethysmography (PPG). Fifteen patients are administered 10 ml 0.25% of bupivacaine, ten patients are administered 10 ml 0.5%, and 17 patients are administered 40 ml 0.0625%. tt,f decreases as a function of the patient's age and blood pressure, both before and after the sympathetic block, owing to the decrease in arterial compliance with age and blood pressure. The time delay tt,f increases after the epidural treatment by 10.1+/-7.0 and by 16.8+/-10.8 ms for the 0.25% and the 0.5% concentrations, respectively. The time delay increase for the lowest concentration is not statistically significant. The toe-finger time delay change is found to reflect the haemodynamic changes induced by the sympathetic block with higher reliability than the routine methods of skin temperature or arterial blood pressure. PMID- 11217890 TI - Resistance training enhances the stability of sensorimotor coordination. AB - Strategies for the control of human movement are constrained by the neuroanatomical characteristics of the motor system. In particular, there is evidence that the capacity of muscles for producing force has a strong influence on the stability of coordination in certain movement tasks. In the present experiment, our aim was to determine whether physiological adaptations that cause relatively long-lasting changes in the ability of muscles to produce force can influence the stability of coordination in a systematic manner. We assessed the effects of resistance training on the performance of a difficult coordination task that required participants to synchronize or syncopate movements of their index finger with an auditory metronome. Our results revealed that training that increased isometric finger strength also enhanced the stability of movement coordination. These changes were accompanied by alterations in muscle recruitment patterns. In particular, the trained muscles were recruited in a more consistent fashion following the programme of resistance training. These results indicate that resistance training produces functional adaptations of the neuroanatomical constraints that underlie the control of voluntary movement. PMID- 11217891 TI - In vivo behaviour of human muscle tendon during walking. AB - In the present study we investigated in vivo length changes in the fascicles and tendon of the human gastrocnemius medialis (GM) muscle during walking. The experimental protocol involved real-time ultrasound scanning of the GM muscle, recording of the electrical activity of the muscle, measurement of knee- and ankle-joint rotations, and measurement of ground reaction forces in six men during walking at 3 km h(-1) on a treadmill. Fascicular lengths were measured from the sonographs recorded. Musculotendon complex length changes were estimated from anatomical and joint kinematic data. Tendon length changes were obtained combining the musculotendon complex and fascicular length-change data. The fascicles followed a different length-change pattern from those of the musculotendon complex and tendon throughout the step cycle. Two important features emerged: (i) the muscle contracted near-isometrically in the stance phase, with the fascicles operating at ca. 50 mm; and (ii) the tendon stretched by ca. 7 mm during single support, and recoiled in push-off. The behaviour of the muscle in our experiment indicates consumption of minimal metabolic energy for eliciting the contractile forces required to support and displace the body. On the other hand, the spring-like behaviour of the tendon indicates storage and release of elastic-strain energy. Either of the two mechanisms would favour locomotor economy PMID- 11217892 TI - Small variations in multiple parameters account for wide variations in HIV-1 set points: a novel modelling approach. AB - Steady-state levels of HIV-1 viraemia in the plasma vary more than a 1,000-fold between HIV-positive patients and are thought to be influenced by several different host and viral factors such as host target cell availability, host anti HIV immune response and the virulence of the virus. Previous mathematical models have taken the form of classical ecological food-chain models and are unable to account for this multifactorial nature of the disease. These models suggest that the steady-state viral load (i.e. the set-point) is determined by immune response parameters only. We have devised a generalized consensus model in which the conventional parameters are replaced by so-called 'process functions'. This very general approach yields results that are insensitive to the precise form of the mathematical model. Here we applied the approach to HIV-1 infections by estimating the steady-state values of several process functions from published patient data. Importantly, these estimates are generic because they are independent of the precise form of the underlying processes. We recorded the variation in the estimated steady-state values of the process functions in a group of HIV-1 patients. We developed a novel model by providing explicit expressions for the process functions having the highest patient-to-patient variation in their estimated values. Small variations from patient to patient for several parameters of the new model collectively accounted for the large variations observed in the steady-state viral burden. The novel model remains in full agreement with previous models and data. PMID- 11217893 TI - The basic depression ratio of the host: the evolution of host resistance to microparasites. AB - The basic reproduction ratio R0 occupies a central position in the theory of host pathogen interactions. However, this quantity stresses the role of the pathogen. This paper proposes an additional, more host-centred char acterization using the basic depression ratio D0. This quantity is the number of host individuals per infected by which the infected host population is depressed below its uninfected level. This paper shows that a baseline criterion for the evolution of host resistance to microparasites is that resistance evolves to minimize D0. This parallels the result for pathogen virulence where R0 is maximized. The tension between these two criteria is noted. The framework established allows a discussion of trade-offs between aspects of the pathogen-free host biology and the host pathogen interaction. For certain linear and convex trade-offs it is shown that the strain with the lowest transmission parameter beta wins (despite the fact that it has the lowest intrinsic birth rate a). For corresponding concave trade-offs, either the strain with minimum beta and a or the strain with maximum beta and a wins. Finally the connection with the techniques of adaptive dynamics is made. Evolutionary singular points are shown to occur at extrema of D0. The evolutionary attainment of the results is discussed. PMID- 11217894 TI - Trade-offs in the evolution of virulence in an indirectly transmitted macroparasite. AB - The adaptive trade-off theory for the evolution and maintenance of parasite virulence requires that virulence be genetically correlated with other fitness characteristics of the parasite. Many theoretical models rely on a positive correlation between virulence and transmissibility. They assume that high parasite replication rates are associated with a high probability of transmission (and, hence, increased parasite fitness), but also with high levels of damage to the host (high virulence). Schistosomes are macroparasites with an indirect life cycle involving a mammalian and a molluscan host. Here we demonstrate, through the development of five substrains, a genetic basis for schistosome virulence. We used these substrains further in order to investigate the presence of parasite fitness traits that were genetically correlated with virulence. High virulence in the (mouse) definitive host was, as predicted, positively correlated with parasite replication. In contrast, in the (snail) intermediate host high virulence was associated with low parasite replication rates. Variation in infectivity to and parasite replication in the definitive host was suggested as a compensating mechanism for the maintenance of virulence in the snail host. This is the first report of a trade-off in parasite reproductive success across hosts in an indirectly transmitted macroparasite. PMID- 11217895 TI - Basis of the trade-off between parasitoid resistance and larval competitive ability in Drosophila melanogaster. AB - Drosophila melanogaster can be artificially selected for increased resistance against parasitoid wasps that attack the larvae. Lines selected for greater resistance are poorer larval competitors under conditions of resource scarcity. Here we investigated the mechanistic basis of this apparent trade-off. We found that resistant lines have approximately twice the density of haemocytes (blood cells) than that of controls. Haemocytes are involved in encapsulation, the chief cellular immune defence against parasitoids. We have previously shown that resistant lines feed more slowly than controls and hypothesize that limiting resources are being switched from trophic to defensive functions. PMID- 11217896 TI - Complex social structure, alliance stability and mating access in a bottlenose dolphin 'super-alliance'. AB - Large brain size in mammals has been related to the number and complexity of social relationships, particularly social alliances within groups. The largest within-group male alliance known outside of humans is found in a social network (> 400) of Indian Ocean bottlenose dolphins (Tursiops aduncus) in Shark Bay Western Australia. Members of this dolphin 'super-alliance' cooperate against other alliances over access to females. Males within the super-alliance form temporary trios and occasionally pairs in order to consort with individual females. The frequent switching of alliance partners suggests that social relationships among males within the super-alliance might be relatively simple and based on an equivalence rule', thereby allowing dolphins to form large alliances without taxing their 'social intelligence'. The equivalence model predicts that the 14 males in the super-alliance should not exhibit differences in alliance stability or partner preferences. However, data from 100 consortships do not support the equivalence hypothesis. The 14 males exhibited striking differences in alliance stability and partner preferences suggesting that the super-alliance has a complex internal structure. Further, within the super alliance, alliance stability correlates with consortship rate, suggesting that differentiated relationships within the super-alliance are based on competition for access to females. PMID- 11217897 TI - Unifying the relationships of species richness to productivity and disturbance. AB - Although species richness has been hypothesized to be highest at 'intermediate' levels of disturbance, empirical studies have demonstrated that the disturbance diversity relationship can be either negative or positive depending on productivity On the other hand, hypothesized productivity diversity relationships can be positive, negative or unimodal, as confirmed by empirical studies. However, it has remained unclear under what conditions each pattern is realized, and there is little agreement about the mechanisms that generate these diverse patterns. In this study, I present a model that synthesizes these separately developed hypotheses and shows that the interactive effects of disturbance and productivity on the competitive outcome of multispecies dynamics can result in these diverse relationships of species richness to disturbance and productivity The predicted productivity diversity relationship is unimodal but the productivity level that maximizes species richness increases with increasing disturbance. Similarly, the predicted disturbance diversity relationship is unimodal but the peak moves to higher disturbance levels with increasing productivity Further, these patterns are well explained by the opposite effects of productivity and disturbance on competitive outcome that are suggested by the change in community composition along these two environmental gradients: higher productivity favours superior competitors while higher disturbance levels favour inferior competitors. PMID- 11217898 TI - Coexistence under positive frequency dependence. AB - Negative frequency dependence resulting from interspecific interactions is considered a driving force in allowing the coexistence of competitors. While interactions between species and genotypes can also result in positive frequency dependence, positive frequency dependence has usually been credited with hastening the extinction of rare types and is not thought to contribute to coexistence. In the present paper, we develop a stochastic cellular automata model that allows us to vary the scale of frequency dependence and the scale of dispersal. The results of this model indicate that positive frequency dependence will allow the coexistence of two species at a greater rate than would be expected from chance. This coexistence arises from the generation of banding patterns that will be stable over long time-periods. As a result, we found that positive frequency-dependent interactions over local spatial scales promote coexistence over neutral interactions. This result was robust to variation in boundary conditions within the simulation and to variation in levels of disturbance. Under all conditions, coexistence is enhanced as the strength of positive frequency-dependent interactions is increased. PMID- 11217899 TI - Reaction norms with bifurcations shaped by evolution. AB - Two versions of a model for the evolution of seasonal polyphenism investigate the evolution of reaction norm bifurcation and branching. The first version is without a specific submodel for morphological development and the second has an explicit developmental map. Version 1 is evolutionarily relatively unconstrained: (i) reaction norms are specified by matrices containing the probabilities of occurrence of environment-phenotype combinations, (ii) all conceivable reaction norm matrices are reachable through a sequence of mutations, and (iii) small as well as large mutational effects occur. This version is used to find the evolutionarily stable strategy favoured by the population ecology that is characterized by stabilizing viability selection with a cyclically fluctuating selection optimum. When the strength of selection is large and when the lag between initiation of development and selection on mature phenotype is not a multiple of half the period of the environmental cycle, a branching reaction norm evolves. In the second model version, branching reaction norms occur for certain parameter combinations of the developmental submodel, but the evolution of this pattern is often constrained. The evolutionary trajectory becomes trapped in a local selective optimum for the parameters of the developmental system. Substantial developmental noise evolves, but mutations that produce a selectively advantageous branching pattern do not occur from there. PMID- 11217900 TI - Warmer springs disrupt the synchrony of oak and winter moth phenology. AB - Spring temperatures have increased over the past 25 years, to which a wide variety of organisms have responded. The outstanding question is whether these responses match the temperature-induced shift of the selection pressures acting on these organisms. Organisms have evolved response mechanisms that are only adaptive given the existing relationship between the cues organisms use and the selection pressures acting on them. Global warming may disrupt ecosystem interactions because it alters these relationships and micro-evolution may be slow in tracking these changes. In particular, such shifts have serious consequences for ecosystem functioning for the tight multitrophic interactions involved in the timing of reproduction and growth. We determined the response of winter moth (Operophtera brumata) egg hatching and oak (Quercus robur) bud burst to temperature, a system with strong selection on synchronization. We show that there has been poor synchrony in recent warm springs, which is due to an increase in spring temperatures without a decrease in the incidence of freezing spells in winter. This is a clear warning that such changes in temperature patterns may affect ecosystem interactions more strongly than changes in mean temperature. PMID- 11217901 TI - Deferred costs of compensatory growth after autumnal food shortage in juvenile salmon. AB - Growing animals are often able to offset the effects of periods of reduced food availability by subsequently undergoing a phase of elevated compensatory or 'catch-up' growth. This indicates that growth rates are not normally maximized even when food is not limiting, suggesting that fast growth may be costly. Here, we show experimental evidence of a long-term deferred cost of compensatory growth after a period of food shortage. Juvenile salmon subjected to a short-lived low food regime in autumn subsequently entered a hyperphagic phase, leading to complete restoration of lipid reserves and partial recovery of lost skeletal growth relative to controls. However, several months later they entered a prolonged phase of poorer performance (despite food now being freely available), so that by the following spring they were substantially smaller than controls and had lower lipid reserves for their body size. The incidence of sexual maturation in males the following breeding season was also reduced. Salmon thus appear to trade off the benefits of short-term restoration of fat stores prior to winter against long-term performance. PMID- 11217902 TI - Microbial diversity, producer-decomposer interactions and ecosystem processes: a theoretical model. AB - Interactions between the diversity of primary producers and that of decomposers- the two key functional groups that form the basis of all ecosystems--might have major consequences on the functioning of depauperate ecosystems. I present a simple ecosystem model in which primary producers (plants) and decomposers (microbes) are linked through material cycling. The model considers a diversity of plant organic compounds and a diversity of microbial species. Nutrient recycling efficiency from organic compounds to decomposers is then the key parameter that controls ecosystem processes (primary productivity, secondary productivity, producer biomass and decomposer biomass). The model predicts that microbial diversity has a positive effect on nutrient recycling efficiency and ecosystem processes through either greater intensity of microbial exploitation of organic compounds or functional niche complementarity, much like in plants. Microbial niche breadth and overlap should not affect ecosystem processes unless they increase the number of organic compounds that are decomposed. In contrast, the model predicts that plant organic compound diversity can only have a negative effect or, at best, no effect on ecosystem processes, at least in a constant environment. This creates a tension between the effects of plant diversity and microbial diversity on ecosystem functioning, which may explain some recent experimental results. PMID- 11217903 TI - Testing demographic models of effective population size. AB - Due to practical difficulties in obtaining direct genetic estimates of effective sizes, conservation biologists have to rely on so-called 'demographic models' which combine life-history and mating-system parameters with F-statistics in order to produce indirect estimates of effective sizes. However, for the same practical reasons that prevent direct genetic estimates, the accuracy of demographic models is difficult to evaluate. Here we use individual-based, genetically explicit computer simulations in order to investigate the accuracy of two such demographic models aimed at investigating the hierarchical structure of populations. We show that, by and large, these models provide good estimates under a wide range of mating systems and dispersal patterns. However, one of the models should be avoided whenever the focal species' breeding system approaches monogamy with no sex bias in dispersal or when a substructure within social groups is suspected because effective sizes may then be strongly overestimated. The timing during the life cycle at which F-statistics are evaluated is also of crucial importance and attention should be paid to it when designing field sampling since different demographic models assume different timings. Our study shows that individual-based, genetically explicit models provide a promising way of evaluating the accuracy of demographic models of effective size and delineate their field of applicability. PMID- 11217904 TI - Genealogical portraits of speciation in montane grasshoppers (genus Melanoplus) from the sky islands of the Rocky Mountains. AB - Grasshoppers in the genus Melanoplus have undergone a radiation in the 'sky islands' of western North America, with many species originating during the Pleistocene. Despite their recent origins, phylogenetic analyses indicate that all the species exhibit monophyletic or paraphyletic gene trees. The objectives of this study were to determine whether the monophyletic genealogies are the result of a bottleneck at speciation and to investigate the extent to which the different phylogenetic states of eight species (i.e. monophyletic versus paraphyletic gene trees) can be ascribed to the effects of speciation. A coalescent simulation was used to test for a bottleneck at speciation in each species. The effective population sizes and demographic histories of species were compared across taxa to evaluate the possibility that the paraphyly versus monophyly of the species reflects differential rates of lineage loss rather than speciation mode. While coalescent analyses indicate that the monophyly of Melanoplus species might not be indicative of bottlenecks at speciation, the results suggest that the paraphyletic gene trees may reflect the demography of speciation, involving localized divergences in the ancestral species. With respect to different models of Pleistocene divergence, the data do not support a model of founder-effect speciation but are compatible with divergence in allopatric refugia. PMID- 11217905 TI - Genetic and morphometric differentiation between island and mainland southern elephant seal populations. AB - We compare genetic (both nuclear and mitochondrial) and morphometric measures between two putative populations of southern elephant seal (Mirounga leonina), and interpret the results in the context of data from mark-recapture and satellite-telemetric studies. One population is on the Argentine mainland, while the other is 2,400 km away on South Georgia island. We found pronounced differentiation at the mitochondrial DNA (mtDNA) control region that was distinct from the pattern of variation seen among island rookeries. Some morphometric characters and seven out of ten nuclear-DNA markers also showed differentiation between the island and mainland sites. Diversity at nuclear markers was high in both populations but mtDNA diversity was low in the mainland population, suggesting a founder event and little subsequent immigration of females. Morphological differences may suggest different selective environments at the two sites. PMID- 11217906 TI - Alpha1-antitrypsin Pi phenotypes S and Z in Spain: an analysis of the published surveys. AB - The aim of the present study was to review published surveys on allelic frequencies S and Z in Spanish populations to evaluate the validity of the reported data. Thirty-four studies published since 1965 were retrieved by MEDLINE, Index Medicus and consultations with experts. The criteria for studies selection were (i) sample size > or = 250 individuals; (ii) alpha-1-antitrypsin phenotyping determination performed by means of crossed antigen-antibody electrophoresis or isoelectrofocusing; (iii) S and Z reported outcomes with an upper 95% CI smaller than mean + 2 SD, a lower 95% CI smaller than mean - 2 SD, and the following ratio: 100 x (95%CI upper limit - 95%CI lower limit)/allelic frequency, for both S and Z, included in the mean +/- 2 SD interval. Thirteen out of 34 surveys retrieved complied with the proposed criteria for S gene frequency analysis and 11 fulfilled the criteria for Z. The greatest frequency for S type is in the north-west of the country (149 alleles per 1000 in Galicians natives), while frequencies in the rest of the country are approximately 100 alleles per 1000. The greatest frequency for Z type has been reported in newborn infants from Valladolid (20.8) and in a randomly selected general population of Asturias (19.7). In the rest of Spain, Z frequencies range from 1.5 to 15 alleles per 1000 genes. PMID- 11217907 TI - In patients with chronic bronchitis a four week trial with inhaled steroids does not attenuate airway inflammation. AB - Systemic corticosteroids have been recommended as a therapeutic option in patients with moderate to severe COPD. In an early stage of the disease, i.e. chronic bronchitis with mild or no airflow obstruction, a trial with inhaled steroids could reveal potential benefits, particularly in terms of a modulation of airway inflammation. We therefore investigated the effect of inhaled fluticasone (1000 microg day(-1)) on markers of airway inflammation in 19 patients with chronic bronchitis (mean+/-SEM FEV1, 83.4+/-3.0% predicted; FEV1/VC, 67.5+/-2.4%) in a double-blind, cross-over, placebo-controlled manner. Visits were performed before and after two 4-week treatment periods. separated by a 4-week washout period. Lung function, the concentration of exhaled nitric oxide, differential cell counts in induced sputum and the number of cells positive for iNOS, as well as the levels of LDH, ECP, neutrophil elastase and IL 8 in sputum supernatants were determined. Although the total cell number decreased significantly after fluticasone (geometric mean 12.3 vs. 7.7 x 10(6)/ml; P<0.05) it was not significantly different from the change observed after placebo (14.2 vs. 10.6 x 10(6)/ml; n.s.). None of the other parameters showed statistically significant changes after fluticasone or placebo and the results did not depend on the presence of airway hyperresponsiveness. We conclude that in patients with chronic bronchitis short-term treatment with inhaled corticosterids did not improve lung function or inflammatory parameters to an extent which was statistically significant as compared to spontaneous variability. PMID- 11217908 TI - Sensitization and exposure to pet allergens in asthmatics versus non-asthmatics with allergic rhinitis. AB - In sensitized subjects with allergic rhinitis (AR) or asthma, allergen exposure provokes symptoms. Among non-asthmatics with AR, an association between allergen sensitization, pollen season and lower airway inflammation has been demonstrated. Our aims were to compare AR and asthma with regard to patterns of allergen sensitization, the degree of airway hyperresponsiveness (AHR) and levels of exhaled nitric oxide (ENO). Finally, we wanted to relate our findings to previous or current exposure to household pets. Four hundred and thirty-one adolescents with different clinical phenotypes were randomly selected from a large-scale epidemiological survey. They were investigated with allergy screening, measurements of ENO and a methacholine bronchoprovocation test. Sensitization to pet allergens (cat, dog and horse) was associated with increased AHR and ENO both in asthmatics and non-asthmatics with AR. The risk of being sensitized to cat allergens was significantly reduced in those who had kept cats vs. those who had never kept them. Keeping dogs or horses did not influence the risk of being sensitized to the respective allergens. Only in steroid-naive, non-smoking asthmatics, a trend towards increased ENO in those sensitized and exposed to cat or dog allergens was seen. Although sensitization towards pet allergens was associated with inflammation in the lower airways irrespective of clinical phenotype, keeping pets did not increase the risk of being sensitized to pet allergens. PMID- 11217909 TI - The ACE gene polymorphism and cough threshold for capsaicin after cilazapril usage. AB - Persistent dry cough is an occasional but clinically important adverse reaction to angiotensin I-converting enzyme (ACE) inhibitors (ACEI). Its reported incidence is variable, and why cough occurs in only certain individuals has been unclear. An insertion/deletion (I/D) polymorphism of the ACE gene is associated with serum ACE activity. We have previously shown that susceptibility to cough induced by ACEI is associated with this polymorphism such that patients with genotype II are more susceptible to cough than patients with other genotypes. In order to confirm and extend our previous observation, we conducted a randomized, placebo-controlled, double-blind, cross-over study in 10 healthy volunteers with genotype II and 10 with genotype DD. The cough threshold was determined by the concentration of inhaled capsaicin causing two or more coughs. After the usage of an ACEI, cilazapril, for 4 weeks, changes in the cough threshold in subjects with genotype II [before: 6.6+/-3.7 nM (mean+/-SD); after: 5.0+/-4.6 nM] significantly differed from those in subjects with genotype DD (before: 9.0+/-9.4 nM; after: 9.3+/-9.1 nM). Skin responses to intradermal bradykinin, which is a substrate of ACE and tussigenic, were significantly increased in subjects with genotype II (before: 1.6+/-0.6 vs. after: 2.6+/-0.5 cm2, P<0.05) but not in subjects with genotype DD (before: 1.4+/-0.5 vs. after: 1.6+/-0.6 cm2, n.s.) after usage of cilazapril. By contrast, skin responses to intradermal substance P did not change in subjects with either genotype. These findings provide further evidence of a link between ACEI-induced cough and I/D polymorphism of the ACE gene and suggest that ACEIs induce cough by modulating the tissue level of bradykinin. PMID- 11217910 TI - Clinical equivalence of salmeterol/fluticasone propionate in combination (50/100 microg twice daily) when administered via a chlorofluorocarbon-free metered dose inhaler or dry powder inhaler to patients with mild-to-moderate asthma. AB - This multi-centre, randomized, double-blind, double-dummy, parallel-group study was designed to investigate the hypothesis of equivalent efficacy and comparable safety of two inhaled presentations of salmeterol/fluticasone propionate combination product (SALM/FP) 50/100 microg administered twice daily to patients with mild-to-moderate asthma for 12 weeks. The delivery systems were a 25/50 microg strength hydrofluoroalkane (HFA) metered-dose inhaler (MDI) and a Diskus inhaler (50/100 microg strength). A third group received FP 100 microg twice daily via a chlorofluorocarbon MDI (50 microg strength). A total of 497 patients aged 11-79 years with reversible airways obstruction who were symptomatic on inhaled corticosteroid (ICS) therapy and had room for improvement in lung function were randomized to treatment in a double-blind, parallel-group design (SALM/FP MDI: n=165; SALM/FP Diskus: n=167; FP MDI: n=165) for 12 weeks. A total of 383 patients completed the study according to the protocol. According to the primary efficacy variable, increase in mean morning PEF over weeks 1-12, the two inhaled presentations of SALM/FP were clinically equivalent (adjusted mean increases 43 and 46 l min(-1); treatment difference 3 l min(-1); 95% confidence interval: -6 to 11 l min(-1)). Equivalence was also demonstrated by all secondary efficacy measures. The SALM/FP MDI was significantly superior to the FP MDI for increase in mean morning PEF (treatment difference 19 l min(-1); P<0.001) and for all secondary measures except FEV1 and symptom-free nights. There was no significant difference between the groups with respect to adverse events and serum cortisol levels. These results demonstrate that the SALM/FP 25/50 microg HFA MDI (two inhalations twice daily) is clinically equivalent to the SALM/FP 50/100 microg Diskus (one inhalation twice daily). Patients switching to SALM/FP from other MDI-based asthma treatments may now do so without a change of delivery device. PMID- 11217911 TI - Pseudomonas aeruginosa in cystic fibrosis: cross-infection and the need for segregation. AB - Evidence-based reasons for segregation of patients colonized with Pseudomonas aerugionsa in the outpatient setting are unclear. To clarify local decisions, Pseudomonas genotyping of the local environment, patients and patient contacts was undertaken in 1993. The hospital environment was re-swabbed in 1997. Pseudomonas genotyping of old and new patients attending the North Staffordshire cystic fibrosis clinic has subsequently been undertaken and more recently been repeated on an annual basis to assess whether the same Pseudomonas genotypes can be found in both the environment and in patients, and whether the same Pseudomonas genotype can be transferred from one patient to another. No Pseudomonas genotype found in the local environment in 1993 or in 1997 has been found in any of our patients. Nine children attending the same special school for many years and sharing the same physiotherapy facilities showed no evidence of cross-infectivity. Except for siblings living in the same household our cross infectivity rate is very low and where cross-infection has potentially occurred the level of contact between these patients has been minimal. This study does not support the suggestion that patients with cystic fibrosis attending the North Staffordshire clinic and colonized with Pseudomonas aeruginosa should be segregated from non-colonized patients. PMID- 11217912 TI - Increased nitric oxide in exhaled air after intake of a nitrate-rich meal. AB - Exhaled and nasal NO (ENO, NNO) have been suggested as markers for inflammation in lower and upper respiratory tract respectively. It is still unknown how a number of factors, apart from airway inflammation, can influence NO levels. The aim of this study was to determine the effect of a nitrate-rich meal on ENO and NNO. Sixteen healthy subjects were observed during 1 week on normal diet before a nitrate-restricted diet was introduced in the next. On day 3 of the second week they were made to ingest a nitrate rich meal. ENO, NNO, plasma nitrate and plasma L-arginine were followed before the meal and afterwards for 3 h. ENO and NNO as well as plasma nitrate and plasma L-arginine were significantly elevated after the nitrate-rich meal. The median maximal increase of ENO and NNO was 47% and 13% respectively. We found a moderate but significant correlation between the rise in plasma nitrate and ENO (r(s)=0.57, P=0.027) but none between plasma nitrate and NNO (r(s)=-0.02, P=0.95). As nitrate in the diet seems to substantially influence the levels of ENO it is important either to restrict or register the intake of nitrate-rich food prior to measuring ENO. PMID- 11217913 TI - Quality of life and health-related quality of life measures. PMID- 11217914 TI - Re: Dose proportionality of fluticosone proportionate hydrofluoroalkane pressurized metered dose inhalers (pMDIS) and comparability with chlorofluorocarbon pMDIS. PMID- 11217915 TI - Critical evaluation of guidelines for the treatment of lower respiratory tract bacterial infections. PMID- 11217917 TI - CoMFA-based comparison of two models of binding site on adenosine A1 receptor. AB - A set of 32 N6-substituted adenosines and 22 8-substituted xanthines with affinity for adenosine A1 receptors was subjected to three-dimensional quantitative structure-affinity relationship analysis using comparative molecular field analysis (CoMFA). The aim was to compare two modes of binding to the receptor--'N6-C8' and 'N6-N7'. Good models with high predictive power and stability were obtained. A comparison of these models gives the following results: (a) Inclusion of both steric and electrostatic fields in CoMFA generates better predictive models compared to models based on steric or electrostatic fields alone. (b) The 'N6-N7' CoMFA models are slightly better than the 'N6-C8' ones. (c) Steric restriction exists around the N6-H in the 'N6-N7' steric field map, which is absent in the 'N6-C8' steric field map. This report demonstrates that the 'N6-N7' mode of binding is a further development of the 'N6-C8' model with a slightly better predictive ability and more accurate steric and electrostatic overlaps between agonists and antagonists. PMID- 11217916 TI - A search for sources of drug resistance by the 4D-QSAR analysis of a set of antimalarial dihydrofolate reductase inhibitors. AB - A set of 18 structurally diverse antifolates including pyrimethamine, cycloguanil, methotrexate, aminopterin and trimethoprim, and 13 pyrrolo[2,3-d pyrimidines were studied using four-dimensional quantitative structure-activity relationship (4D-QSAR) analysis. The corresponding biological activities of these compounds include IC50 inhibition constants for both the wild type, and a specific mutant type of Plasmodium falciparum dihydrofolate reductase (DHFR). Two thousand conformations of each analog were sampled to generate a conformational ensemble profile (CEP) from a molecular dynamics simulation (MDS) of 100,000 conformer trajectory states. Each sampled conformation was placed in a 1 A cubic grid cell lattice for each of five trial alignments. The frequency of occupation of each grid cell was computed for each of six types of pharmacophore groups of atoms of each compound. These grid cell occupancy descriptors (GCODs) were then used as a descriptor pool to construct 4D-QSAR models. Models for inhibition of both the 'wild' type and the mutant enzyme were generated which provide detailed spatial pharmacophore requirements for inhibition in terms of atom types and their corresponding relative locations in space. The 4D-QSAR models indicate some structural features perhaps relevant to the mechanism of resistance of the Plasmodium falciparum DHFR to current antimalarials. One feature identified is a slightly different binding alignment of the ligands to the mutant form of the enzyme as compared to the wild type. PMID- 11217918 TI - Comparative molecular field analysis (coMFA) study of epothilones-tubulin depolymerization inhibitors: pharmacophore development using 3D QSAR methods. AB - A three-dimensional quantitative structure-activity relationship (3D QSAR) study has been carried out on epothilones based on comparative molecular field analyses (CoMFA) using a large data set of epothilone analogs, which are potent inhibitors of tubulin depolymerization. Microtubules, which are polymers of the a/beta tubulin heterodimer, need to dissociate in order to form the mitotic spindle, a structure required for cell division. A rational pharmacophore searching method using 3D QSAR procedures was carried out and the results for the epothilones are described herein. One-hundred and sixty-six epothilone analogs and their depolymerization inhibition properties with tubulin were used as a training set. Over a thousand molecular field energies were generated and applied to generate the descriptors of QSAR equations. Using a genetic function algorithm (GFA) method, combined with a least square approach, multiple QSAR models were considered during the search for pharmacophore elements. Each GFA run resulted in 100 QSAR models, which were ranked according to their lack of fit (LOF) scores, with a total of 40 GFA runs having been performed. The 40 best QSAR equations from each run had adequate fitted correlation coefficients (R from 0.813 to 0.863) and were of sufficient statistical significance (F value from 7.2 to 10.9). The pharmacophore elements for epothilones were studied by investigating the hit frequency of descriptors (i.e. the sampling probabilities of grid points from the GFA studies) from the set of the 4,000 top scoring QSAR equations. By comparing the frequency with which each grid point appeared in the QSAR equations, three candidate regions in the epothilones were proposed to be pharmacophore elements. Two of them are completely compatible with the recent model proposed by Ojima et al. [Proc. Natl. Acad. Sci. USA, 96 (1999) 4256], however, one is quite different and is necessary to accurately predict the activities of all 166 epothilone molecules used in our training set. Finally, by visualizing the 35 most probable grid points, it was found that changes related to the C6, C7, C8, C 12, S20, and C21 atoms of the epothilones were highly correlated to their activity. PMID- 11217919 TI - FILO (field interaction ligand optimization): a simplex strategy for searching the optimal ligand interaction field in drug design. AB - A method (FILO, Field Interaction Ligand Optimization) for obtaining the optimal molecular interaction field was developed on the basis of the Simplex optimization procedure applied to a matrix of interaction energies obtained by performing a GRID computation on a suitable data set. The FILO procedure was tested on a set of nine HIV-1 protease inhibitors with known crystal structures. The results of FILO consist of the optimal molecular interaction field of a putative new ligand with optimal binding affinity. The final FILO model yields R2 and R2(CV) values of 0.993 and 0.936, respectively, and finds eight negative and four positive interaction nodes for the OH probe taken as an example. The eight H bonding interactions pointed out by FILO identified well the binding site AA residues Gly A27, Asp A29, water 501, Gly B48 and Asp A25 of HIV-1 protease. PMID- 11217920 TI - Structure-toxicity relationships of polycyclic aromatic hydrocarbons using molecular quantum similarity. AB - The establishment of quantitative structure-activity relationship (QSAR) models for the toxicity of polycylic aromatic hydrocarbons (PAHs) is described. Two properties, in vitro percutaneous absorption in rat skin and discrete levels of carcinogenic activity, are examined using molecular quantum similarity measures (MQSM). The results show that MQSM produces comparable, or even better, results than other approaches using physicochemical, topological and quantum-chemical molecular descriptors. Furthermore, a careful analysis puts into evidence that most of the information characterized by the original descriptors is in fact contained in the molecular density functions, the basis of MQSM. The present paper, together with several other reported by our laboratory, proves that MQSM might be appropriate theoretical tools for QSAR and computer-aided drug design, comparable to other highly predictive QSAR methodologies. PMID- 11217921 TI - SLATE: a method for the superposition of flexible ligands. AB - A novel program for the superposition of flexible molecules, SLATE, is presented. It uses simulated annealing to minimise the difference between the distance matrices calculated from the hydrogen-bonding and aromaticring properties of two ligands. A method for generating a molecular stack using multiple pairwise matches is illustrated. These stacks are used by the program DOH to predict the relative positions of receptor atoms that could form hydrogen bonds to two or more ligands in the dataset. The methodology has been applied to ligands binding to dihydrofolate reductase, thermolysin. H3 histamine receptors, alpha2 adrenoceptors and 5-HT1D receptors. When there are sufficient numbers and diversity of molecules in the dataset, the prediction of receptor-atom positions is applicable to compound design. PMID- 11217923 TI - Pharmacokinetics of the ganciclovir implant in the silicone-filled eye. AB - PURPOSE: Ganciclovir (GCV) implants are highly effective in delaying the progression of cytomegalovirus (CMV) retinitis. Rhegmatogenous retinal detachments can occur in untreated eyes with CMV retinitis or in eyes treated with anti-CMV therapy, which may include placement of a GCV implant. The clinical management of CMV retinitis and associated retinal detachment often involves the concurrent use of silicone oil and GCV implants. The authors investigated the effect of silicone oil tamponade on intravitreal drug levels achieved with the GCV implant. METHODS: The authors performed gas compression vitrectomy in the right eyes of 29 New Zealand white rabbits. They then inserted a 5-mg GCV implant into the vitreous cavity through an inferotemporal sclerotomy. Saline (1 cc), silicone oil 0.5 cc, or silicone oil 1.0 cc was then injected into the midvitreous cavity of 9, 8, and 12 rabbits, respectively. On postoperative days 21, 42, and 70, the rabbits were killed and the right eyes were immediately collected and stored at -70 degrees C until all samples were obtained. Vitreous was then isolated and drug levels were determined by high-pressure liquid chromatography. RESULTS: Vitreous GCV levels at days 21 and 42 were similar in both the saline-filled and silicone oil-filled eyes. At day 70, GCV levels in both the saline- and silicone-filled eyes were statistically significantly lower than at day 21 (P < 0.05 for all groups). In addition, at day 70, GCV levels in the saline-filled eyes were significantly lower than in silicone-filled eyes (saline versus 0.5 cc oil, P = 0.01; saline versus 1 cc oil, P = 0.09). CONCLUSIONS: Effective GCV levels are maintained in the aqueous phase of the vitreous cavity of eyes with silicone oil tamponade. Ganciclovir levels may be maintained longer in eyes with silicone oil tamponade than in those without. These results support the use of combined GCV implants and silicone oil tamponade in patients with CMV retinitis and associated retinal detachment. PMID- 11217922 TI - Immune recovery vitritis and uveitis in AIDS: clinical predictors, sequelae, and treatment outcomes. AB - PURPOSE: To determine 1) clinical predictors of an inflammatory syndrome associated with cytomegalovirus (CMV) retinitis (immune recovery vitritis or uveitis [IRV or IRU]); 2) clinical sequelae of IRV; and 3) the effect of corticosteroid treatment on visual acuity. METHODS: A cohort study from the AIDS Ocular Research Unit of the University of California, San Diego, and a case series from the Cleveland Clinic consisted of patients who had acquired immunodeficiency syndrome and inactive CMV retinitis who responded to highly active antiretroviral therapy (HAART) with CD4 T-lymphocyte levels >60 cells/mm3. The cohort was followed for a median of 13.5 months following increase in CD4 count. The authors studied the occurrence of IRV, defined as symptomatic (vision decrease and/or floaters) vitritis of 1+ or greater severity associated with inactive CMV retinitis. Macular edema or epiretinal membrane formation was determined by clinical examination and fluorescein angiography. Five eyes were treated with sub-Tenon corticosteroid injections. RESULTS: In the cohort study, 19 (63%) of 30 HAART responders developed IRV (26 eyes). The clinical spectrum of inflammation included vitritis, papillitis, macular edema, and epiretinal membranes. Eyes with CMV surface area >30% of the retina were at the highest risk (relative risk = 4.5) of developing IRV (P = 0.03). During follow-up, inflammation persisted without treatment for a median of 20 weeks and 14 patients (16 eyes) developed macular changes. Treatment resulted in vision improvement without reactivation of retinitis. Histology and immunohistochemistry of associated epiretinal membranes showed evidence of chronic inflammation with a predominant T-lymphocyte cell population. In the case series, 3 (38%) of 8 HAART responders developed IRV (4 eyes). All four eyes were treated and resulted in visual acuity improvement of one line. CONCLUSIONS: Symptomatic IRV or IRU develops in a significant number of patients with CMV retinitis following successful HAART. Eyes with CMV surface area >30% of the retina are at the greatest risk. Eyes with IRV respond favorably to antiinflammatory therapy without reactivation of retinitis. Immune recovery vitritis may be the result of an immunologic reaction to latent CMV antigens in the eye in which T-lymphocytes play a role. PMID- 11217924 TI - Surgery for idiopathic macular holes associated with extensive subretinal fluid. AB - PURPOSE: To study the baseline characteristics and outcomes of surgery for idiopathic macular holes associated with localized macular detachment. METHODS: In this case-control study, eight consecutive patients with idiopathic macular hole associated with localized macular detachment (cases) and 30 randomly selected patients with idiopathic macular hole not associated with macular detachment underwent macular hole surgery. RESULTS: The mean age (62.1 versus 68.2 years; P = 0.086), mean refractive error (-0.13 versus +0.23 diopters; P = 0.68), average duration of symptoms (5.9 versus 4.6 months; P = 0.47), and macular hole stage (P = 0.43) were similar in the cases and controls. The baseline visual acuity ranged from 20/50-20/80 (1 [13%] versus 1 [3%]) to 20/100 20/200 (2 [25%] versus 24 [80.0%]) to < 20/200 (5 [63%] versus 5 [17%]) (P = 0.10). Single-operation anatomic success was achieved in 2 (25%) cases and 24 (80%) controls (P = 0.007). Visual acuity 3 months after the last macular hole surgery was worse in cases compared to controls: > or = 20/40 in 0 versus 6 (20%), 20/50-20/80 in 1 (13%) versus 13 (43%), 20/100-20/200 in 4 (50%) versus 10 (33%), and < 20/200 in 3 (38%) versus 1 (3%) (P = 0.003). The mean improvement in visual acuity was 0.2 logMAR units in cases versus 0.4 logMAR units in controls (P = 0.054). CONCLUSIONS: Surgical outcomes for idiopathic macular hole associated with a localized macular detachment compare poorly with the outcomes for macular hole not associated with extensive surrounding subretinal fluid. PMID- 11217925 TI - Endoscopic vitreoretinal surgery for complicated proliferative diabetic retinopathy. AB - PURPOSE: To evaluate the indication for endoscopic vitreoretinal surgery in proliferative diabetic retinopathy (PDR). METHODS: Chart review of consecutive cases of vitreoretinal surgery for PDR performed by one of the authors (Y.L.F.) over a 2-year period. RESULTS: Endoscopic vitreoretinal surgery was performed in 8 of 41 (19.5%) eyes. The surgical indications were small pupil (3), hyphema (3), pseudophakia with fibrotic posterior capsule (1), and pars plana neovascularization with anterior tractional retinal detachment (6). CONCLUSION: Endoscopic vitreoretinal surgery, by enhancing the visualization of the retroirideal space, is a useful technique in PDR with opaque ocular media and/or neovascularization of the pars plana and ciliary body. PMID- 11217927 TI - Familial primary pulmonary hypertension and associated ocular findings. AB - BACKGROUND: Familial primary pulmonary hypertension (PPH) is a rare, fatal, autosomal dominant disease that results in right heart failure from idiopathic obliteration of the pulmonary arteries. Patients develop stagnation of venous blood flow and elevated venous pressure. METHODS: The authors retrospectively reviewed the clinical records of three patients diagnosed with PPH that was confirmed on the basis of physical examination, chest X-ray, electrocardiogram, and echocardiogram. Cardiac catheterization excluded cardiac shunt and other secondary causes of pulmonary hypertension. RESULTS: Two patients presented with a clinical picture resembling venous stasis retinopathy, and one with bilateral choroidal detachments. Two patients had delayed choroidal filling on fluorescein angiography, which was confirmed in one patient with indocyanine green videoangiography. CONCLUSIONS: Elevated venous pressure found in PPH is responsible for the delayed choroidal perfusion and the reduced venous blood outflow. This explains the clinical findings of venous stasis retinopathy and choroidal detachments seen in these patients. PMID- 11217926 TI - Matrix metalloproteinases in human diabetic and nondiabetic vitreous. AB - PURPOSE: To compare matrix metalloproteinase (MMP) activities in human vitreous samples from patients with diabetic retinopathy (DR) and other vitreoretinal diseases, and to investigate the factors influencing the MMP activities in human DR vitreous samples. METHODS: Thirty-one diabetic and 17 nondiabetic vitreous samples (from nine patients with macular holes and eight patients with epiretinal membranes) were examined. Samples collected at the time of pars plana vitrectomy were subjected to substrate zymography to conduct a quantitative analysis of MMP activity. Immunoblotting against antihuman MMP-1, 2, and 9 was performed to identify MMP in vitreous samples. The effects of posterior vitreous detachment (PVD), vitreous hemorrhage, proliferative membrane, traction detachment, and cystoid macular edema on MMP activities were investigated. RESULTS: All vitreous samples from both DR and non-DR patients showed a single band at the position of 72 kD, corresponding to MMP-2. Another band at 99 kD, corresponding to MMP-9, was detected significantly more often in DR samples than in non-DR samples: 45.2% and 0%, respectively (P = 0.0007). The number of samples showing a band from MMP-9 was significantly higher in partial PVD samples than in complete PVD samples: 66.7% and 15.4%, respectively (P = 0.001). CONCLUSION: The results indicated that MMP-9 may be involved in DR and that partial PVD may be related to the MMP-9 activity in DR. PMID- 11217928 TI - Choroidal granulomas in systemic sarcoidosis. AB - PURPOSE: To evaluate the clinical course, including response to therapy, of patients with macular and peripapillary choroidal granulomas secondary to systemic sarcoidosis. METHODS: This is a retrospective case study and literature review. Nine patients with choroidal granulomas were identified. Eight patients had a tissue biopsy confirming sarcoidosis; one was diagnosed from clinical history and typical gallium scan. Ocular examinations included fundus examination, fluorescein angiography, and visual field examination. Eight patients had magnetic resonance imaging (MRI) scans looking for intracranial granulomas. Treatment consisted of oral prednisone in eight patients (one with concomitant subconjunctival triamcinolone); one patient received no treatment because of good vision and granuloma in the nasal retina. Variables studied included visual acuity (VA), response of granulomas to treatment, time to recurrence, and associated anterior segment findings. RESULTS: Eight of nine patients had a solitary lesion whereas one had multifocal involvement. The granulomas ranged in size from one half to four disk diameters. Eight patients had blurry vision; one was asymptomatic. All nine patients had hilar adenopathy and/or pulmonary parenchymal disease. No patient had nonocular neurologic symptoms and in eight patients who underwent MRI examination no intracranial granulomas were detected. Of the eyes that were treated (n = 8) all had decrease in the size of the choroidal mass at an average of 4 months of treatment. Two had complete resolution. Mean follow-up was 29.2 months. At the time of initial diagnosis only one patient had an active anterior uveitis. Five of nine patients had at least one recurrence. Mean time to recurrence was 7.6 months after discontinuing oral prednisone. The VA at presentation ranged from 20/30 to 20/300. Final VA was 20/30 or better in all patients. CONCLUSIONS: Choroidal granulomas related to systemic sarcoidosis respond well to oral corticosteroids. They may recur but good vision can be maintained. They are not typically associated with concomitant iritis and also do not appear to be associated with intracranial granulomas. PMID- 11217929 TI - Methylprednisolone concentrations in the vitreous and the serum after pulse therapy. AB - PURPOSE: Intravenous (i.v.) pulse of corticosteroids has been used to treat severe eye inflammation from different origins. Whether such large doses result in vitreous levels that differ either in magnitude or duration from more conventional corticotherapy remain unsolved issues. The authors therefore determined levels of methylprednisolone hemisuccinate and methylprednisolone in the vitreous and serum of patients at different times after a single i.v. perfusion of methylprednisolone hemisuccinate. METHODS: Fifty patients scheduled for a first vitrectomy received an i.v. injection of 500 mg hemisuccinate methylprednisolone at different times before surgery (from 15-24 hours). Patients were divided into two groups: those with (n = 21) and without (n = 29) retinal detachment (RD). Pure vitreous samples were analyzed by high-pressure liquid chromatography. RESULTS: Both the ester and the nonester methylprednisolone forms were sampled in the vitreous, showing a slower rate of hydrolysis compared to the serum. On average, the highest concentration of total methylprednisolone in the vitreous was found at 2.5 hours and rapidly decreased for the group of patients with RD. In the group of patients without RD, the highest concentration was reached at 6 hours and then slowly decreased. The antiinflammatory potency in the nondetached retina eyes was approximately 500 times more than in the physiologic vitreous, but despite the route of administration (i.v. or oral), only 1/10 of the corticosteroid serum concentration was measured in the vitreous. CONCLUSION: High concentration of methylprednisolone is achieved by i.v. pulse therapy without changing the kinetic of entry in the vitreous of nondetached retina eyes when compared to conventional oral corticotherapy. Hydrolysis occurs in the vitreous resulting in high rate of active form. Pulse therapy could be considered in cases of severe ocular inflammation involving the posterior segment of the eye. PMID- 11217930 TI - Retinal fixation of traumatic retinal detachment with metallic tacks: a case report with 10 years' follow-up. AB - BACKGROUND: Retinal rupture and detachment caused by traumatic ocular perforation has a poor prognosis without extensive repair procedures. The authors describe the phases of treatment of a complex injury in a 21-year-old man with a traumatic retinal rupture in whom metallic tacks were used for retinal fixation. The report does not include histopathology. METHODS: Observational case report and literature review. The outcome of a 10-year follow-up is evaluated at the latest visit by determining the visual acuity (VA) and by observing the state of retina and tacks. RESULTS: A traumatic retinal rupture with detachment was treated with titanium tacks for retinal fixation. By inserting a total of 13 metallic tacks for the repair of a temporal postequatorial retinal rupture and adjacent retinal detachment a successful outcome was achieved. Two additional operations were performed to reattach the retina of nasal hemisphere in the same eye. One dislodged tack was removed at the final operation. Ten years later, at the last intervention, VA was 12/20 in the injured eye. The retina was completely attached, and the remaining 12 tacks were in place, although six of them were partially pushed up by an encircling band. Proliferative vitreoretinopathy (PVR) was absent, and a relatively narrow circumferential zone of scar tissue adjacent to the row of tacks was visible. The patient occasionally experienced glare in the affected eye, but was otherwise symptom-free. CONCLUSION: Reports of long term experiences with mechanical retinal refixation with metallic tacks are scarce. Especially in extended use, the tacks are claimed to cause several complications, including PVR. Although modern ophthalmic surgery offers a variety of methods for retinal reattachment, the complexity of the damage caused by trauma may lead to a dead end in refixation attempts. Nevertheless, retinal tacks may represent an adjunctive remedy in complex retinal detachment cases. PMID- 11217931 TI - Retinal thickness measurements with optical coherence tomography and the scanning retinal thickness analyzer. AB - PURPOSE: To assess the reproducibility of retinal thickness measurements in normal subjects and to compare foveal thickness using optical coherence tomography (OCT) and the scanning retinal thickness analyzer (RTA). METHODS: Two examiners performed foveal thickness measurements in 24 eyes of 12 healthy subjects using both OCT and the scanning RTA. Intraclass correlation coefficients (ICC) (intra-examiner and inter-examiner) were calculated for the paired foveal thickness measurements obtained with each instrument. RESULTS: The average foveal thicknesses measured with OCT and the scanning RTA were 155.1 +/- 14.9 microm and 107.8 +/- 18.6 microm, respectively. The intra-examiner ICCs from the two sessions using the OCT and the scanning RTA were 0.99 and 0.78 and 0.89 and 0.99, respectively. The inter-examiner ICCs of the OCT and the scanning RTA were 0.99 and 0.99, respectively. There was a significant correlation between the foveal thickness measurements with these two instruments (R2 = 0.629, P < 0.0001). CONCLUSION: The foveal thicknesses measured using OCT and the scanning RTA in healthy subjects agreed with the previously reported data on foveal thickness. Both instruments can reproducibly quantitate foveal thickness. PMID- 11217932 TI - Diagnostic and therapeutic challenges. PMID- 11217933 TI - Bilateral prepapillary loops with unilateral branch retinal artery occlusion following thrombus at the loop apex. PMID- 11217934 TI - Purtscher's retinopathy secondary to airbag injury. PMID- 11217935 TI - Surgical removal of a laser-induced choroidal neovascular membrane. PMID- 11217936 TI - Visual recovery from macular phototoxic injury following cataract surgery. PMID- 11217937 TI - Sector retinitis pigmentosa with bitemporal visual field defects and macular hole. PMID- 11217938 TI - Bilateral ocular ischemic syndrome in Takayasu disease. PMID- 11217939 TI - Epipapillary adenoma of retinal pigment epithelium. PMID- 11217940 TI - Optical coherence tomography and electrophysiology in X-linked juvenile retinoschisis associated with a novel mutation in the XLRS1 gene. PMID- 11217941 TI - Diabetic papillopathy with macular star mimicking clinically significant diabetic macular edema. PMID- 11217942 TI - Surgical management of combined traction and rhegmatogenous retinal detachment associated with persistent fetal vasculature. PMID- 11217943 TI - Central retinal vein occlusion associated with primary pulmonary hypertension. PMID- 11217944 TI - Neovascularization associated with cytomegalovirus retinitis. PMID- 11217945 TI - Retinal and choroidal vascular changes in heterozygous Fabry disease. PMID- 11217946 TI - A case of Alport's syndrome and retinal degeneration. PMID- 11217947 TI - Early versus late removal of retained intraocular foreign bodies. PMID- 11217948 TI - Fungal endophthalmitis after a single intravenous administration of presumably contaminated dextrose infusion fluid. PMID- 11217949 TI - Occurrence of retinoblastoma and uveal melanoma in the same period. PMID- 11217950 TI - Surgical techniques double-bent needle for intraocular injection. PMID- 11217951 TI - Fiberoptic illuminator assisted conventional retinal detachment surgery. PMID- 11217952 TI - Synthesis of novel ganglioside GM4 analogues containing N-deacetylated and lactamized sialic acid: probes for searching new ligand structures for human L selectin. AB - Novel ganglioside GM4 analogues, which contain N-deacetylated or lactamized sialic acid instead of usual N-acetylneuraminic acid, were synthesized in a highly efficient manner. (Methyl 4,7,8,9-tetra-O-acetyl-3,5-dideoxy-5 trifluoroacetamido-D-glycero-alpha-D-galacto-2-nonulopyranosylonate)-(2-->3)-4,6 di-O-acetyl-2-O-benzoyl-D-galactopyranosyl trichloroacetimidate was coupled with 2-(tetradecyl)hexadecanol to give the desired beta-glycoside in high yield. Successive O- and N-deacylation, and saponification of the methyl ester group afforded the N-deacetylated sialyl derivative that was converted by treatment with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in Me2SO into the lactamized sialic acid-containing ganglioside GM4 analogue. PMID- 11217953 TI - The occurrence of internal (1 --> 5)-linked arabinofuranose and arabinopyranose residues in arabinogalactan side chains from soybean pectic substances. AB - CDTA-extractable soybean pectic substances were subjected to enzymatic digestion with arabinogalactan degrading enzymes yielding a resistant polymeric pectic backbone and arabino-, galacto-, and arabinogalacto-oligomers. The complex digest was fractionated using size-exclusion chromatography. Monosaccharide composition analysis, HPAEC fractionation and MALDI-TOF MS analysis of the resulting fractions showed that each contained a mixture of oligosaccharides of essentially the same degree of polymerisation, composed of only arabinose and galactose. MALDI-TOF MS analysis was used for molecular mass screening of oligosaccharides in underivatised HPAEC fractions. The monosaccharide sequence and the branching pattern of oligosaccharides (degree of polymerisation from 4 to 8) were determined using linkage analysis and ES-CID tandem MS analysis of the per-O methylated oligosaccharides in each of the HPAEC fractions. These analyses indicated the presence of common linear (1 --> 4)-linked galacto oligosaccharides, and both linear and branched arabino-oligosaccharides. In addition, the results unambiguously showed the presence of oligosaccharides containing (1 --> 4)-linked galactose residues bearing an arabinopyranose residue as the non-reducing terminal residue, and a mixture of linear oligosaccharides constructed of (1 --> 4)-linked galactose residues interspersed with an internal (1 --> 5)-linked arabinofuranose residue. The consequences of these two new structural features of pectic arabinogalactan side chains are discussed. PMID- 11217954 TI - Reactivity of some sugars and sugar phosphates towards gold(III) in sodium acetate-acetic acid buffer medium. AB - The kinetics of the oxidation of some aldoses and aldose phosphates have been studied spectrophotometrically in sodium acetate-acetic acid buffer medium at different temperatures. The reactions are first order with respect to [Au(III)] and [substrate]. Both H+ and Cl- ions retard the reaction. The reactions appear to involve different gold(III) species, viz. AuCl4-, AuCl3(OH2) and AuCl3(OH)- . The results are interpreted in terms of the probable intermediate formation of free radicals and Au(II). Aldoses react with gold(III) in the order: triose > tetrose > pentose > hexose. The sugar phosphates react with gold(III) at a faster rate than the parent sugars except glucose-1-phosphate, which reacts at slower rates than glucose. A tentative reaction mechanism leading to the formation of products has been suggested. PMID- 11217955 TI - Complexation of trivalent lanthanide cations by galactitol in the solid state. The crystal structure and an FT-IR study of 2NdCl3.galactitol.14H2O. AB - The crystal structure of 2NdCl3.galactitol.14H2O has been determined. The crystal system is triclinic, space group: -1, with unit-cell dimensions: a = 9.736(2), b = 10.396, c = 8.027 A; alpha = 108.05(3), beta = 92.68(3), gamma = 88.44(3) degrees, V= 771.6(3) A3, Z = 2. Each Nd atom is coordinated to nine oxygen atoms, three from the alditol and six from water molecules, with Nd-O distances from 2.461 to 2.552 A. The seventh water molecule is hydrogen-bonded by the hydroxyl hydrogen on O-1 (O-1-H-ll...O-10, 2.639 A). The FT-IR spectra of 2NdCl3.galactitol.14H2O and 2PrCl3.galactitol.14H2O are analogous, and show that Pr and Nd have the same coordination mode. The IR results are consistent with the crystal structures. PMID- 11217956 TI - Systematic analysis of oxidative degradation of polysaccharides using PAGE and HPLC--MS. AB - Oxidation of polysaccharides yields hydroxyaldehydes and hydroxycarboxylic acids. Aldehydes and carboxylic acids were separately conjugated to 8-aminonaphthalene 1,3,6-trisulfonic acid (ANTS) or tyrosine t-butyl ester (TBT). The ANTS-labeled derivatives were separated by molecular size on PAGE gels and detected by fluorescence. TBT-labeled derivatives were separated by reverse phase chromatography on a C18-HPLC column and analyzed by positive ion electrospray mass spectroscopy (HPLC--MS). This combination of procedures allowed a systematic analysis of carbohydrate oxidation products. PMID- 11217957 TI - Studies on the synthesis of 1,2-cis pentofuranosides from S-glycofuranosyl dithiocarbamates, dithiocarbonates and phosphorodithioates. AB - The selectivity in the synthesis of 1,2-cis glycofuranosides from dithiocarbonates, dithiocarbamates and phosphorodithioates is improved by combined use of silver triflate and catalytic amount of hexamethylphosphoramide (HMPA) under mild conditions. PMID- 11217958 TI - X-ray diffraction and high-resolution NMR spectroscopic analysis of 2,4,7,8-tetra O-acetyl-3-deoxy-alpha-D-manno-2-octulopyranosono-1,5-lactone. AB - The X-ray diffraction and high-resolution 1H and 13C NMR spectral data are reported for 2,4,7,8-tetra-O-acetyl-3-deoxy-alpha-D-manno-2-octulopyranosono-1,5 lactone. PMID- 11217959 TI - TEMPO-mediated oxidation of maltodextrins and D-glucose: effect of pH on the selectivity and sequestering ability of the resulting polycarboxylates. AB - Maltodextrins were oxidized to polyglucuronic acids with the ternary oxidation system: NaOCl-NaBr-2,2,6,6-tetramethylpiperidine-l-oxyl (TEMPO). The chemoselective oxidation at the primary alcohol groups was shown to be strongly pH dependent. Oxidation of polysaccharides was best achieved at pH 9.5 in order to minimize depolymerization, whereas oxidation of oligosaccharides required stronger alkaline conditions (pH 11-11.5). The resulting sodium polyglucuronates present interesting sequestering properties, the best of which being obtained from maltodextrins with the highest degrees of polymerization. The same oxidation process allowed the convenient conversion of D-glucose to D-glucaric acid in high yield (> 90%), under strongly basic conditions (pH > 11.5). PMID- 11217960 TI - Synthesis of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid analogues modified at the C-4 and C-9 positions and their behaviour towards sialidase from influenza virus and pig liver membrane. AB - The synthesis of novel 2-deoxy-2,3-didehydro-N-acetylneuraminic acid analogues structurally varied at C-4 and C-9 by transformation from versatile key intermediates and their inhibitory activity against sialidase from influenza virus A and pig liver membrane are described. PMID- 11217961 TI - Contribution of the anomeric effect to the solution and crystal structure of [1S,2S,6S,7s]-1,6-diaza-4,9-dioxa-2,7-dimethoxycarbonylbicyclo[4.4.1]undecane, a condensation product of L-serine methyl ester with formaldehyde. AB - The reaction of L-serine methyl ester hydrochloride (1) with paraformaldehyde (2) in dichloromethane in the presence of triethylamine afforded a novel compound: [lS,2S,6S,7S]-1,6-diaza-4,9-dioxa-2,7-dimethoxycarbonylbicyclo[4.4.1]undecane (4) as a 2:3 adduct of 1 with 2. 1H and 13C NMR spectroscopy were unable to discriminate between two possible symmetrical structures. The latter was unambiguously proved by X-ray crystallography. The crystal structure established: (i) the existence of two identical seven-membered rings each containing a N-C-O grouping; (ii) the existence of a long C-O-C-N-C-N-C-O-C sequence in which each nitrogen belongs simultaneously to a N-C-O (oxazolidine) and to a N-C-N (aminal) motifs; (iii) the existence of a chair-like conformation for both seven-membered rings; (iv) the antiperiplanar geometry of pN-C-O and consequently the manifestation of a strong anomeric effect in both N-C-O groupings, whereas anomeric effect was virtually absent in the N-C-N sequence, as corroborated by bond distances and bond angles. Chemical shifts, coupling constants and NOE effects confirm that the conformational features of 4 are preserved in solution. PMID- 11217962 TI - Acid-catalyzed dehydrative cyclization of 4-(D-galacto -pentitol-1-yl)-2-phenyl 2H-1,2,3-triazole. synthesis and anomeric configuration of D-lyxo-C-nucleoside analogs. AB - Dehydration of 4-(D-galacto-pentitol-1-yl)-2-phenyl-2H-1,2,3-triazole with 20% methanolic sulfuric acid afforded the anomeric pairs of nucleosides, 4-(alpha-D lyxopyranosyl)-2-phenyl-2H-1,2,3-triazole (major component) and its beta-anomer, as well as 4-(alpha-D-lyxofuranosyl)-2H-1,2,3-triazole and its beta-anomer. The four anomeric C-nucleosides were separated by chromatography, and their structure and anomeric configuration were determined by periodate oxidation, acylation, and NMR spectroscopy as well as mass spectrometry. The anomeric assignment from optical rotation was not in agreement with final structure assignment and represented a violation of the Hudson isorotation rules. NOE studies and X-ray diffraction measurements confirmed the anomeric configuration. PMID- 11217963 TI - Biosynthesis of lactosamine in bovine mammary gland. AB - Lactosamine (beta-D-Galp-(1-->4)-D-GlcN) was isolated from bovine milk sampled after intravenous infusion of glucosamine through the jugular vein of a lactating cow. The chemical structure was established by 2D NMR spectroscopy and electrospray ionisation mass spectrometry (ESIMS). Selected ion monitoring liquid chromatography-mass spectrometry (SIMLC-MS) of the perbenzoylated carbohydrate fraction showed the presence of the novel disaccharide in the milk sample after infusion, but not in the control bovine milk sample. The results showed the uptake of glucosamine in bovine mammary gland, and also indicated that a part of glucosamine was metabolised to the product lactosamine. PMID- 11217964 TI - Syntheses of the L-manno and some other analogs of the terminal determinants of the O-PS of Vibrio cholerae O:1. AB - Analogs of the methyl alpha-glycosides of the terminal residues of the O-specific polysaccharides (O-PS) of Vibrio cholerae O:1, serotype Inaba and Ogawa, have been prepared as probes to study their interaction with anti V. cholerae O:1 antibodies. They differ from the termini of the respective O-PSs in anomeric or absolute configuration of perosamine, position of the O-methyl group in D perosamine, and nature of the N-acyl side chain. PMID- 11217965 TI - Expression and action pattern of Botryotinia fuckeliana (Botrytis cinerea) rhamnogalacturonan hydrolase in Pichia pastoris. AB - The cDNA sequence coding for the complete rhamnogalacturonan hydrolase (RGase) of Botryotinia fuckeliana (Botrytis cinerea) was introduced into Pichia pastoris and expressed under the control of the alcohol oxidase promoter. The RGase was secreted into the medium of the yeast driven by the alpha-factor secretion peptide and could be purified using the C-terminal His6-tag fusion. RGase activity was measured using a traditional reducing end assay with linseed rhamnogalacturonan (RG) as the substrate, or with an assay using a fluorescent RG oligomer as the substrate and detection and identification of hydrolysis products by capillary zone electrophoresis (CZE). Both methods showed the recombinant enzyme to have a specific activity of about ten units per milligram of protein. Since the CZE method allows identification of the hydrolysis products, it was used to show that the RGase lacks a multiple attack mechanism and needs at least five GalA-Rha repeating disaccharides to be active. This finding is contrary to the action pattern of the native RGase of Aspergillus aculeatus which has the same substrate length requirement, but exhibits multiple attack, leading to products containing only two and three Rha-GalA repeat units without the appearance of intermediate sized fragments. No plant cell wall degrading enzymes were detected in the culture medium of un-transformed P. pastoris, thus the recombinant enzyme, devoid of extraneous activities, can be applied for fine structural studies on cell walls. PMID- 11217966 TI - Structural studies of the O-specific polysaccharide of Vibrio cholerae O8 using solvolysis with triflic acid. AB - The O-specific polysaccharide (OPS) of Vibrio cholerae 08 was isolated by mild acid degradation of the lipopolysaccharide and studied by two-dimensional NMR spectroscopy, including NOESY and heteronuclear multiple-bond correlation (HMBC) experiments. The OPS was found to have a tetrasaccharide repeating unit with the following structure: --> 4)-beta-D-Glcp NAc3NAcylAN-(1 --> 4)-beta-D-Manp NAc3NAcAN-(1 --> 4)-alpha-L-Gulp NAc3NAcA-(1 --> 3) -beta-D-QuipNAc4NAc-(1 --> where QuiNAc4NAc is 2,4-diacetamido-2,4,6-trideoxyglucose, GlcNAc3NAcylAN is 2 acetamido-3-(N-formyl-L-alanyl)amino-2,3-dideoxyglucuronamide, ManNAc3NAcAN is 2,3-diacetamido-2,3-dideoxymannuronamide, and GulNAc3NAcA is 2,3-diacetamido-2,3 dideoxyguluronic acid. The OPS was stable towards acid hydrolysis and solvolysis with anhydrous hydrogen fluoride, but could be cleaved selectively with trifluoromethanesulfonic (triflic) acid by the glycosidic linkages of beta QuiNAc4NAc and alpha-GulNAc3NAcA. The structures of the oligosaccharides obtained that were elucidated by electrospray ionization (ESI) MS and NMR spectroscopy, confirmed the OPS structure. PMID- 11217967 TI - Polysaccharides of green Arabica and Robusta coffee beans. AB - Two independent procedures for the quantitative determination of the polysaccharide content of Arabica Caturra (Coffea arabica var. Caturra) and Robusta ROM (Coffea canephora var. ROM) green coffee beans showed that they both contained identical amounts of polysaccharide. Cell wall material (CWM) was prepared from the beans and partial solubilisation of component polysaccharides was effected by sequential extraction with water, 1 M KOH, 0.3% NaClO2, 4 M KOH and 8 M KOH. The monosaccharide compositions of the CWMs were similar, although Arabica beans contained slightly more mannose than Robusta. In the latter, more arabinogalactan was solubilised during preparation of the CWM and the water soluble fraction of the CWM contained higher amounts of galactomannan than in Arabica. Linkage analysis indicated that the galactomannans possessed unbranched to branched mannose ratios between 14:1 and 30:1 which is higher than previously reported. No major difference in the structural features of the galactomannans between species was found. The arabinogalactans were heterogeneous both with regard to the degree of branching and the degree of polymerisation of their arabinan side-chains. Compared to Arabica, Robusta appeared to contain greater amounts of arabinogalactans with longer side chains. It is concluded that there was no detectable difference between the Arabica and Robusta varieties of this study in their absolute polysaccharide content or in the gross structural features of their galactomannans. Differences were apparent both in the structural features and ease of solubility of the arabinogalactans but a more detailed study of several varieties of Arabica and Robusta will be required to determine whether these differences occur consistently between species. PMID- 11217968 TI - Studies toward the site specific incorporation of sugars into proteins: synthesis of glycosylated aminoacyl-tRNAs. AB - A series of glycosylated serine derivatives was synthesized from peracetylated sugars and Fmoc-protected serine; these were chemically esterified with the tris (tetrabutylammonium) salt of pdCpA. The fully protected and deprotected glycosylated aminoacyl pdCpAs were ligated enzymatically to an abbreviated tRNA (tRNA-C(OH)) to provide the title compounds that are key intermediates in the elaboration of glycoproteins using readthrough of a nonsense codon. PMID- 11217969 TI - Syntheses and reactions of 5-O-acetyl-1,2-anhydro-3-O-benzyl-alpha-D-ribofuranose and beta-D-lyxofuranose, 5-O-acetyl-1,2-anhydro-3,6-di-O-benzyl- and 1,2-anhydro 5,6-di-O-benzoyl-3-O-benzyl-beta-D-mannofuranose, and 6-O-acetyl-1,2-anhydro-3,4 di-O-benzyl-alpha-D-glucopyranose and -beta-D-talopyranose. AB - The title compounds 5-O-acetyl-1,2-anhydro-3-O-benzyl-alpha-D-ribofuranose and 5 O-acetyl-1,2-anhydro-3-O-benzyl-beta-D-lyxofuranose, and 6-O-acetyl-1,2-anhydro 3,4-di-O-benzyl-alpha-D-glucopyranose and 6-O-acetyl-1,2-anhydro-3,4-di-O-benzyl beta-D-talopyranose, and 5-O-acetyl-1,2-anhydro-3,6-di-O-benzyl-beta-D mannofuranose and 1,2-anhydro-5,6-di-O-benzoyl-3-O-benzyl-beta-D-mannofuranose have each been synthesized from the corresponding 2-O-tosylate and 1-free hydroxyl intermediates by base-initiated intramolecular S(N)2 ring closure in almost quantitative yields. Acetyl and benzoyl groups were not affected in the ring closure reactions. Condensation of 6-O-acetyl-1,2-anhydro-3,4-di-O-benzyl alpha-D-glucopyranose and 5-O-acetyl-1,2-anhydro-3,6-di-O-benzyl-beta-D mannofuranose with 1,2:3,4-di-O-isopropylidene-alpha-D-galactopyranose in the presence of ZnCl2 as the catalyst afforded the 1,2-trans-linked 6-O-acetyl-3,4-di O-benzyl-beta-D-glucopyranosyl-(1-->6)-1,2:3,4-di-O-isopropylidene-alpha-D galactopyranose and 5-O-acetyl-3,6-di-O-benzyl-alpha-D-mannofuranosyl-(1-->6) 1,2:3,4-di-O-isopropylidene-alpha-D-galactopyranose as the sole products in satisfactory yields, while condensation of 5-O-acetyl-1,2-anhydro-3-O-benzyl-beta D-lyxofuranose with 3-O-benzyl-1,2-O-isopropylidene-alpha-D-xylofuranose yielded the 1,2-trans-linked 5-O-acetyl-3-O-benzyl-alpha-D-lyxofuranosyl-(1-->5)-3-O benzyl-1,2-O-isopropylidene-alpha-D-xylofuranose as the sole product in a good yield. The 6-O-acetyl group in the glycosyl donor, 6-O-acetyl-1,2-anhydro-3,4-di O-benzyl-alpha-D-glucopyranose, did not influence the stereoselectivity of the ring-opening-coupling reaction. PMID- 11217970 TI - Regioselective and stereoselective benzoylation of 2-N-protected 4,6-O-ketal derivatives of D-glucosamines with 1-(benzoyloxy)benzotriazole. AB - A highly regioelective and stereoselective benzoylation of the 2-N-protected 4,6 O-ketal derivatives of D-glucosamines with 1-(benzoyloxy)benzotriazole that affords the corresponding beta anomeric benzoates in excellent yields is described herein. PMID- 11217971 TI - Anomalous Zemplen deacylation reactions of alpha- and beta-D-mannopyranoside derivatives. AB - Reaction of mono-, di-, and trisaccharide derivatives of methyl beta-D- and octyl beta-D-mannopyranosides bearing ester groups at isolated and non-isolated positions on the same molecule, under Zemplen conditions (catalytic amount of sodium methoxide in methanol) gave partially deacylated compounds, in which the O acyl groups were retained at isolated sites. In the case of one disaccharide, all the benzoyl groups remained intact at the reducing end, while all the acetyl functions were removable from the nonreducing end. In another case, both isolated ester groups at positions 2 and 4 were retained at the reducing end. The isolated 2-O-acyl groups on methyl alpha-D-mannopyranoside compounds were more labile than on the corresponding beta-mannosides under the same conditions. The mechanism of the reaction may be different for ester groups at isolated or non-isolated positions. In the latter case, acyl migration may take place and carry acyl groups into a less hindered position. PMID- 11217972 TI - Synthesis, analysis and reduction of 2-nitropropyl starch. AB - Granular 2-nitropropyl potato starch was synthesized by reaction with 2 nitropropyl acetate in an aqueous suspension. Nitroalkylation occurs preferentially with the amylose fraction of potato starch, as was confirmed by leaching experiments and digestion of the modified starch with alpha-amylase. The 2-nitropropyl substituent is a mixture of the nitroalkane and nitronic acid tautomer. Some grafting occurs and to a lesser extent additional reactions (formation of carbonyls and oximes) of the nitro group take place. After catalytic hydrogenation of water soluble 2-nitropropyl starch only a small amount of the nitro functionality was reduced to the corresponding amine. Reduction of granular 2-nitropropyl starch with sodium dithionite did not go to completion and led to a complex mixture of starting material, several intermediates and side products (for example sulfamates). PMID- 11217973 TI - Reactions of some 2- and 4-O-triflylglycopyranosides with MeLi, t-BuOK, and pyridine. AB - As an extension of our previous work on secondary triflates of carbohydrates [El Nemr, A.; Tsuchiya, T. Tetrahedron Lett. 1995, 36, 7665-7668. El Nemr, A.; Tsuchiya, T.; Kobayashi, Y. Carbohydr. Res. 1996, 293, 31-59. El Nemr, A.; Tsuchiya, T. Carbohydr. Res. 1997, 301, 77-87. El Nemr, A.; Tsuchiya, T. Carbohydr. Res. 1997, 303, 267-281], the reaction modes of several methyl 2- and 4-O-triflyl-D-glycopyranosides with MeLi (strong base), t-BuOK (moderately strong base), and pyridine (weak base) have been studied. This paper describes the reactions of 3-O-benzyl-4,6-O-benzylidene-2-O-triflyl-D-gluco and mannopyranosides with MeLi to give mainly the corresponding 2-C-methyl derivatives through alpha-elimination, with t-BuOK to give either the 2,3 unsaturated compounds through beta-elimination or detriflyl 2-ols, and with hot pyridine to give the corresponding 2-pyridinium salts with inversion (except for the 2-O-triflyl-alpha-D-mannopyranoside (8)). 2,3,6-Tri-O-benzyl-4-O-triflyl alpha-D-gluco and -mannopyranosides were also examined similarly. PMID- 11217974 TI - Structures of the O4 and O18 antigens of Stenotrophomonas maltophilia: a case of enantiomeric repeating units. AB - The O-specific side-chain polymers of lipopolysaccharides from the reference strains for Stenotrophomonas maltophilia serogroups 04 and O18 are both xylosylated rhamnans. In the 04 polymer, both sugar components are the D isomers, whereas the O18 polymer contains only the L isomers. By means of NMR spectroscopy, methylation analysis and Smith degradation, the repeating unit of the 04 polymer was identified as a doubly-branched pentasaccharide of the structure shown below. The O18 polymer is based on the enantiomeric pentasaccharide, but the xylosyl substituent at the 4-position is apparently absent from some units. The polymers closely resemble the O antigens found in Xanthomonas campestris pathovars. [structure: see text] PMID- 11217975 TI - Chemical structure of the core oligosaccharide of aerotolerant Campylobacter jejuni O:2 lipopolysaccharide. AB - The structure of the core oligosaccharide of aerotolerant Campylobacter jejuni 0:2 lipopolysaccharide was determined and found to contain 3-deoxy-D-manno octulosonic acid (Kdo), L-glycero-D-manno-heptose (LD-Hep), D-galactose, D glucose, and phosphorylethanolamine (PEtn). Based on 1H, 13C and 31P NMR spectroscopic studies including 2D COSY, TOCSY, ROESY and heteronuclear 1H-31P and HMQC experiments it was established that the oligosaccharide has the following structure: [structure: see text]. PMID- 11217976 TI - Structure of an acidic polysaccharide from a marine bacterium Pseudoalteromonas distincta KMM 638 containing 5-acetamido-3,5,7,9-tetradeoxy-7-formamido-L-glycero L-manno-nonulosonic acid. AB - An acidic polysaccharide was obtained from the lipopolysaccharide of Pseudoalteromonas distincta strain KMM 638, isolated from a marine sponge, and found to contain D-GlcA, D-GalNAc, 2-acetamido-2,6-dideoxy-D-glucose (D-QuiNAc) and two unusual acidic amino sugars: 2-acetamido-2-deoxy-D-galacturonic acid (D GalNAcA) and 5-acetamido-3,5,7,9-tetradeoxy-7-formamido-L-glycero-L-manno nonulosonic acid (Pse5Ac7Fo, a derivative of pseudaminic acid). Oligosaccharides were derived from the polysaccharide by partial acid hydrolysis and mild alkaline degradation and characterised by electrospray ionisation (ESI) MS and 1H and 13C NMR spectroscopy. Based on these data and NMR spectroscopic studies of the initial and O-deacetylated polysaccharides, including quaternary carbon detection, 2D COSY, TOCSY, ROESY, H-detected 1H,13C HMQC and HMBC experiments, the following structure of the branched pentasaccharide repeating unit was established: [structure: see text]. PMID- 11217977 TI - Physicochemical properties and structure of large, medium and small granule starches in fractions of normal barley endosperm. AB - Normal barley grain was milled to flour with a machine used to polish brewers' rice from the surface layer to the center. Large (18.4 microm, median size), medium (12.3 microm) and small (2.2 microm) granule starches were isolated from classified flours. Their physicochemical properties and fine structure were investigated. The percentage (w%) of large granules decreased from the surface layer to the center, while the amounts of medium and small granules increased. Although all the starch granules were an A-type crystal, the relative crystallinity varied from 22.0 to 27.4%. The DPn of the amyloses was around 1600 and similar for all the samples. But the amylose content of the starches varied from 21.9 to 26.4%. Also, the amylopectins showed differences in DPn (around 5700 7900) and chain-length distribution between granule size or fractions. The transition temperature ranges and the enthalpy values of the starch granules differed with granule size. The gelatinization properties showed no correlation with any of the parameters, except the enthalpy value and relative crystallinity (gamma = +0.73). The findings suggested that the structural characteristics of the starches in classified flours of normal barley differed essentially from those of waxy barley. PMID- 11217978 TI - Internal structure of the starch granule revealed by AFM. AB - Atomic force microscopy images of sectioned native corn starch granules show evidence of the well-known radial organisation of the starch macromolecules, with the less-ordered hilum region near to the centre. Native granules show blocks 400 500 nm in size that span the growth rings. Lintnerised starch granules, where a mild acid hydrolysis has been used to remove the amorphous and less crystalline parts of the granule, clearly show smaller 'blocklets' within the rings approximately 10-30 nm in size. This level of organisation within the growth rings corresponds to the blocklet or superhelix structures that have been proposed in the literature for the association or clustering of amylopectin helices. Mechanical property imaging techniques have provided enhanced contrast to view this morphology, and shown the deformability of the starch structure under contact mode imaging conditions. PMID- 11217979 TI - Preparation of novel polysubstituted chiral cyclohexanone derivatives containing a quaternary carbon by Ferrier reaction. AB - 2-C- and 3-C-[(2'-chloro)pyrid-5'-yl]-hex-5-enopyranosides were synthesized from 4,6-O-benzylidene acetals in three steps. By treatment with mercury or palladium salts, the corresponding cyclohexanones could be obtained. The stereochemistry of these reactions was highly dependent on the substitution pattern of the starting material and the nature and concentration of the catalyst. PMID- 11217980 TI - An efficient synthesis of methyl 2,3-anhydro-alpha-D-ribofuranoside. AB - An efficient synthesis of methyl 2,3-anhydro-alpha-D-ribofuranoside is reported. Its preparation is achieved via a four-step sequence from methyl 2,3,5-tri-O benzoyl-alpha-D-arabinofuranoside in 74% overall yield. PMID- 11217981 TI - Structural determination of the phytotoxic mannan exopolysaccharide from Pseudomonas syringae pv. ciccaronei. AB - The structural determination was performed of a mannan exopolysaccharide from the gram negative bacterium Pseudomonas syringae pv. ciccaronei, which is the pathogenic agent responsible for the leaf spots of carob plants. The structure, obtained by chemical, enzymatic and spectroscopic methods, consisted of a backbone of alpha-(1-->6)-linked mannopyranose units with 80% substituted at C-2 by mono-, di- and trisaccharide side chains. In addition, terminal glucose units and phosphate groups were found to be present. This is, to the best of our knowledge, the first report of a mannan exopolysaccharide structure from a phytopathogenic bacterium. The pure polysaccharide showed phytotoxic effects, i.e., chlorosis and necrosis on tobacco leaves. PMID- 11217982 TI - Structure of the O16 antigen of Stenotrophomonas maltophilia. AB - A polysaccharide containing D-ribose, N-acetyl-D-glucosamine, and N-acetyl-D mannosamine was isolated from the phenol-soluble lipopolysaccharide extracted from defatted cell walls of the reference strain (560) for serogroup O16 of Stenotrophomonas maltophilia. The results of methylation analysis, chemical degradations, and NMR spectroscopy showed that the polysaccharide is based on a branched trisaccharide repeating-unit of the structure shown below. Although ribose was absent from about half of the units in the isolated polymer, the regularity and spacing of the ladder observed on SDS-PAGE of the parent lipopolysaccharide indicate that this was an artefact of the mild acid hydrolysis used to release the polymer. On the other hand, the effects of mild alkaline hydrolysis on the polymer indicated partial O-acetylation. [structure: see text] PMID- 11217983 TI - Isolation and NMR characterisation of a (4-O-methyl-D-glucurono)-D-xylan from sugar beet pulp. AB - Stable aqueous suspensions of purified and homogenised sugar beet pulp (SBP) cellulose were subjected to various TFA treatments which induced a flocculation of the suspension and the release of a number of polysaccharides. Among these, a 4-O-methyl glucuronoxylan was isolated and characterized by 1H and 13C NMR spectroscopy. In this polysaccharide the molar proportions of D-Xyl and 4-O-Me-D GlcA were found to be 7:1. The presence of a glucuronoxylan at the surface of the cellulose microfibrils is very likely involved in the stability of the suspensions. To our knowledge, the presence of a 4-O-methyl-glucuronoxylan in the sugar beet cells has not been described previously. PMID- 11217984 TI - Is contact allergy in man lifelong? An overview of patch test follow-ups. AB - In contradistinction from certain strains of mice, contact allergy in man is hypothesized to be either lifelong or at least to last for years. We examined follow-up studies on contact allergy, as evaluated by patch testing, attempting to quantify its natural history. The allergens include colophonium, gold sodium thiosulfate, nickel, and cobalt. At present, due to technical limitations, we cannot state in quantitative terms whether contact allergy in man is lifelong and whether its clinical manifestations change. Thus, we list some criteria for future studies which may help resolve the above question. PMID- 11217985 TI - Modified short-term guinea pig sensitization tests for detecting contact allergens as an alternative to the conventional test. AB - The conventional adjuvant and patch test (APT) method of guinea pig sensitization testing was modified in 2 ways, s-APT and s-APT(2), in order to shorten the test period. These short-term test methods consist of 72-h closed application of test material with intradermal injection of emulsified Freund's complete adjuvant (E FCA) for 1st induction, 48-h closed application of test material with (s-APT) or without (s-APT(2)) intradermal injection of E-FCA on the 7th day for 2nd induction, and open application on the 14th day for challenge. They were compared with conventional APT by using 8 allergenic chemicals (formaldehyde, nickel sulfate, cobalt sulfate, ethyl-p-aminobenzoate (benzocaine), isoeugenol, 2 mercaptobenzothiazole, 2,4-dinitrochlorobenzene (DNCB) and 1-phenylazo-2-naphthol (Sudan I)). The short-term methods gave similar results to those of conventional APT in terms of mean response, sensitization rate and sensitization potency (challenge concentration that induces a mean response equal to 1.0). Thus, our short-term methods, which are capable of evaluating skin sensitization within 17 days, are sufficiently sensitive to detect potentially hazardous contact allergens. PMID- 11217986 TI - Another look at seasonal variation in patch test results. A multifactorial analysis of surveillance data of the IVDK. Information Network of Departments of Dermatology. AB - There is conflicting evidence concerning seasonal variability of patch test results and no evidence concerning the influence of season on weak-positive, possibly false-positive, irritant reactions, which was analysed in the present study. Data collected in the German Information Network of Departments of Dermatology (IVDK) 1992 to 1997 were combined with external environmental data on temperature and absolute humidity in Germany, and bivariate as well as logistic regression analyses performed concerning the association between reactivity to selected allergens and air temperature and absolute humidity on the respective days of patch testing. Between 39,239 and 41,629 patients had been tested with the 4 allergens considered here. Only formaldehyde exhibited a distinct increase in questionable or irritant as well as weak-positive reactions associated with dry, cold weather. Methylchloroisothiazolinone/methylisothiazolinone and lanolin alcohol showed only a weak, and epoxy resin no, association with climatic conditions. The results indicate that weak-positive reactions, at least to formaldehyde as a prototype of an allergen which is at the same time a marginal irritant, may sometimes be irritant rather than allergic. Patients showing these should be re-tested to improve the poor reproducibilty observed with this allergen. PMID- 11217987 TI - Occupational contact allergy to (meth)acrylates. AB - Among 13,833 patients suspected of contact dermatitis examined during the years 1978-1999, occupational contact allergy to (meth)acrylates was diagnosed in 31 patients. The 3 most common sensitizers were ethyleneglycol dimethacrylate (17 positive patch tests), 2-hydroxyethyl methacrylate (14) and triethyleneglycol dimethacrylate (6). The aim of this report was to assess the different occupations and industries responsible for occupational sensitization to (meth)acrylates. 14 of the 31 patients work in the dental sector, either as a dentist or as a student of dental technology, where (meth)acrylate-containing dental prostheses and dental composites are mainly responsible for allergy to (meth)acrylates. An increasing trend in dermatological problems related to the expansion of the use of (meth)acrylates is clearly reflected in the patient population of our dermatology department. PMID- 11217988 TI - Nickel release from coins. AB - Nickel allergy is the most frequent contact allergy and is also one of the major background factors for hand eczema. The clinical significance of nickel release from coins was discussed when the composition of euro coins was decided. Current European coinage is dominated by cupro-nickel coins (Cu 75; Ni 25); other nickel containing and non-nickel alloys are also used. Nickel release from used coinage from the UK, Sweden and France was determined. It was shown that nickel ions are readily available on the surface of used coins. After 2 min in artificial sweat, approximately 2 microg of nickel per coin was extracted from cupro-nickel coins. Less nickel was extracted from non-nickel coins. Nickel on the surface was mainly present as chloride. After 1 week in artificial sweat approximately 30 microg/cm2 was released from cupro-nickel coins: less nickel was released from coins made of other nickel alloys. Theoretically, several microg of nickel salts may be transferred daily onto hands by intense handling of high-nickel-releasing coins. PMID- 11217989 TI - Incidence of work-related hand eczema during apprenticeship: first results of a prospective cohort study in the car industry. AB - Data on the incidence and prevalence of occupational contact dermatitis (OCD) are scarce, and most of our knowledge about OCD is derived from clinical case reports or clinical studies of in-and out-patients. Therefore, we investigated in the epidemiological, prospective Audi cohort study (PACO study) the incidences of work-related hand eczema in different apprenticeships of Audi AG. In total, 2078 apprentices were investigated at the start of their apprenticeship and systematically followed up over a 3-year period. At the end of the study, information on 2042 (98.2% follow-up) apprentices was available. The 1-year cumulative incidences of hand eczema were 9.2% (95%-confidence interval 7.8-10.7) in metalworkers, 8.8% (95%-CI 7.0-10.7) in other blue-collar workers, and 4.6% (95%-CI 2.3-8.1) in white-collar apprentices. The 3-year cumulative incidences of hand eczema were 15.3% (95%-CI 13.6-17.2) in metalworkers, 14.1% (95%-CI 11.8 16.5) in other blue-collar workers, and 6.9% (95%-CI 4.0-10.9) in white-collar apprentices. In females, the cumulative incidence of hand eczema was higher compared to men (1-year incidence 10.1%, 95%-CI 7.7-13.0, versus 8.3%, 95%-CI 7.1 9.5; 3-year incidence 16.1%, 95%-CI 13.1-19.5 versus 13.6%, 95%-CI 12.2-15.2). In some occupations, like cooks, tool mechanics, milling cutters and varnishers, the incidence of hand eczema was significantly increased. In those occupations, however, no job change was necessary, and no notifiable occupational contact dermatitis occurred. The incidence was not uniformly distributed over the 3-year period. Within the first 6 months, a particularly high rate of hand eczema occurred, which then declined and remained steady at a lower rate over the 2nd and the 3rd years. The results of our study give important suggestions for preventive measures at the workplace and effective occupational pre-employment advices. PMID- 11217990 TI - Contact allergy to Disperse Blue 106 and Disperse Blue 124 in German and Austrian patients, 1995 to 1999. AB - Between 1995 and 1999, 1986 patients were tested in the 31 participating centres of the Information Network of Departments of Dermatology (IVDK), all of them members of the German Contact Dermatitis Research Group, with a textile dyes series containing Disperse Blue (DB) 106 and 124, and since 1997 also with a mix of both. 86 patients (4.3%) reacted positively to DB 106 and/or DB 124; with good concordance between the 2 allergens (Cohen's weighted kappa 0.72), and the single allergens and the mix (kappa=0.75 in both cases), which had been tested in parallel in 969 and 975 patients, respectively. In contrast, concordance between DB 106/124 and p-phenylenediamine and p-aminoazobenzene, respectively, was poor. Some 70% of positive reactions to DB 106/124 had current clinical relevance. Furthermore, a significant increase in the proportion of DB 106/124-positive patients among those tested was found from 1995 to 1999. Hence, DB 106/124 are important allergens deserving close monitoring. The use of a mix of DB 106 and DB 124 seems justified in view of the close chemical similarity of both compounds. If possible, the presence of the allergen(s) in individual textiles considered causative should be checked by thin layer or column chromatography. PMID- 11217991 TI - Allergic contact dermatitis caused by a nickel-containing headband. PMID- 11217992 TI - Contact dermatitis from organophosphorus pesticides. PMID- 11217993 TI - Type I allergy to natural rubber latex and Type IV allergy to rubber chemicals in children with risk factors. PMID- 11217994 TI - Phytodermatitis from Ranunculus damascenus. PMID- 11217995 TI - Occupational and systemic contact dermatitis with photosensitivity due to vitamin B6. PMID- 11217996 TI - Generalized eczema due to codeine. PMID- 11217997 TI - Occupational allergic contact dermatitis in hairdressers due to glutaraldehyde. PMID- 11217998 TI - Palmar contact dermatitis due to (meth)acrylates. PMID- 11217999 TI - Occupational allergic contact dermatitis from benzophenone-4 in hair-care products. PMID- 11218000 TI - Fixed-drug eruption caused by allylisopropylacetylurea. PMID- 11218001 TI - Sorbitan sesquioleate as an allergen. PMID- 11218002 TI - Allergic contact dermatitis from pharmaceutical grade BHA in Timodine, with no patch test reaction to analytical grade BHA. PMID- 11218003 TI - Allergic contact dermatitis from enoxolone. PMID- 11218004 TI - Occupational allergic contact dermatitis from ethylhexylzinc dithiophosphate and fatty acid polydiethanolamide in cutting fluids. PMID- 11218005 TI - Active sensitization by epoxy in Leica immersion oil. PMID- 11218007 TI - Drug eruption induced by cefcapene pivoxil hydrochloride. PMID- 11218006 TI - Allergic and irritant occupational contact dermatitis from Alstroemeria. PMID- 11218008 TI - Periorbital allergic contact dermatitis from oxybuprocaine. PMID- 11218009 TI - Primula dermatitis mimicking lichen planus. PMID- 11218011 TI - Epiploic appendagitis: color Doppler sonographic findings. AB - The aim of this study was to analyze the color Doppler sonographic findings in primary epiploic appendagitis. Color Doppler sonographic findings of ten patients with primary epiploic appendagitis were reviewed. The following sonographic features were analyzed: identification of a mass adjacent to the colonic wall; identification of spotty color areas with arterial flow in this mass and detection of abnormalities of the colonic wall adjacent to the infiltrated fatty tissue. A well-delineated hyperechoic mass adjacent to the colonic wall was detected in each patient with sonography. No colonic wall abnormalities were observed nor color Doppler signal in and around the hyperechoic area. Absence of flow at color Doppler sonography is an additional feature of epiploic appendagitis. PMID- 11218010 TI - Irritant contact dermatitis of the hands following thoracic sympathectomy. PMID- 11218013 TI - Mycobacterium genavense infection in AIDS: imaging findings in eight patients. AB - This retrospective study included eight HIV-positive patients with a M. genavense infection. Seven of these patients had a CT scan of the abdomen and a US examination, whereas one patient with pulmonary symptoms had conventional chest radiographs and thin-section CT scan of the thorax. Multiple large retroperitoneal and mesenteric lymph nodes were demonstrated in seven patients; low-attenuation centers within enlarged nodes were identified in two patients. On CT scans two cases showed circumferential wall thickening of the proximal small bowel with a deep ulceration in one of these patients. Additional findings included focal lesions in the liver (n = 1), spleen (n = 2), splenomegaly (n = 6), and hepatomegaly (n = 4). The CT scans from the thoracic examination demonstrated multiple diffuse nodular infiltrates in both lungs. M. genavense infection should be considered in the differential diagnosis of AIDS patients with CD4 counts below 100 cells/mm3 presenting with abdominal lymphadenopathy, multinodular or homogeneous hepatosplenic enlargement and circumferential thickening of the small bowel wall. PMID- 11218012 TI - Off-site evaluation of liver lesion detection by Gd-BOPTA-enhanced MR imaging. AB - The aim of this study was to determine the efficacy of Gd-BOPTA-enhanced MRI in liver lesion detection in comparison with unenhanced MRI and dynamic CT. The image sets of 148 of 151 patients enrolled in a multicenter German phase-III trial were evaluated by two independent radiologists unaffiliated with the investigating centers. Patients underwent a routine MRI protocol comprising T2- and T1-weighted spin-echo and T1-weighted gradient-echo (GE) sequences pre and 1 h post 0.1 mmol/kg Gd-BOPTA (Bracco-Byk Gulden, Konstanz, Germany). Additionally, a serial T1-weighted GE scan was performed after administration of the first half of the dose. All patients underwent dynamic contrast-enhanced CT. The evaluation was performed with regard to the number and size of lesions detected per patient by each modality or sequence. Furthermore, all pre CM and pre + post CM image sets were analyzed for number of lesions per patient. Both readers detected significantly more lesions in the contrast-enhanced image set compared with the unenhanced image set (32 and 39 %, respectively; p < 0.0001). While contrast enhanced CT detected a similar number of lesions to unenhanced MRI, it was clearly inferior to contrast-enhanced MRI (reader 1: p = 0.0117; reader 2: p = 0.0225). Of the T1-weighted scans performed, the dynamic and late T1-weighted GE exams contributed most to the increased lesion detection rate (reader 1: p = 0.0007; reader 2: p = 0.0037). The size of the smallest lesion detected by means of MRI was significantly larger in the pre-CM image sets than in the pre + post CM image sets (reader 1: p = 0.001; reader 2: p < 0.0001). Gd-BOPTA-enhanced MRI detected significantly smaller lesions than contrast-enhanced CT (reader 1: p = 0.0117; reader 2: p = 0.0925). Gd-BOPTA-enhanced MR imaging improves liver lesion detection significantly over unenhanced MRI and dynamic CT. PMID- 11218014 TI - Helical CT without contrast in choledocholithiasis diagnosis. AB - The goal of this study was to determine the diagnostic value of the helical CT without contrast in suspected cases of choledocholithiasis, comparing this test with endoscopic retrograde cholangiopancreatography (ERCP). Forty patients with possible choledocholithiasis were studied prospectively. There were 23 women and 17 men, ranging in age from 24 to 91 years. Helical CT was performed immediately before ERCP (time interval between the two procedures was less than 1 h). A biliary area previously selected was studied with a technique of pitch 1 and slice thickness of 3.2 mm. Average time was 30 s. Reconstruction with different increments and windows were made. Stone presence was evaluated in bile duct and Vater's ampulla. Biliary dilation was evaluated too. Endoscopic retrograde cholangiopancreatography found stones in 19 patients and absence of stones in 20. One case was failed, but stones in bile duct were demonstrated during intraoperative cholangiography. Helical CT demonstrated stones in 15 of the 19 patients with positive ERCP. There were no false positives with CT. Patients without stones in ERCP were also negative in CT. The patient having the failed ERCP was considered positive in CT. The CT sensitivity was 80% and specificity was 100%, with an accuracy of 90%. Helical CT without contrast has sensitivity and specificity good enough to be used as a screening technique in patients with suspected choledocholithiasis. PMID- 11218015 TI - Focal nodular hyperplasia: imaging findings. AB - Focal nodular hyperplasia is an uncommon benign hepatic tumor that continues to pose diagnostic dilemmas. Imaging techniques are of great value in diagnosis of this tumor. In this article we present the US, CT, MR imaging, scintigraphy, and angiography findings. The demonstration of a central vascular scar is very helpful. Although the radiologic features may be diagnostic, many atypical cases must be differentiated from other benign or malignant hepatic tumors. In these cases excisional biopsy and histopathologic examination are necessary to determine a definite diagnosis. PMID- 11218016 TI - US and CT diagnosis of a twisted lipomatous appendage of the falciform ligament. AB - Pathologic conditions of the falciform ligament leading to surgical intervention are extremely uncommon. We report a case of twisted lipomatous appendage of this ligament, demonstrated by US and CT. To our knowledge, there have been no previous reports of this entity. The extraperitoneal nature of the lesion was found by realtime sonography, but CT only was able to characterize its lipomatous nature and relationship with the falciform ligament. This lesion should be considered in the differential diagnosis of intra-abdominal focal fat infarction (IFFI), a recent vocable essentially regrouping infarction of omentum and epiploic appendages. PMID- 11218017 TI - Gastrointestinal stromal tumor of the rectum. AB - Gastrointestinal stromal tumors (GISTs) are characterized by remarkable variability in their differentiation potential, but most of these lesions do not display convincing smooth muscle or neuronal differentiation. The GISTs arising from the rectum or anal canal are extremely uncommon. We present a case of immunohistochemically proven GIST of the rectum, which was characterized by homogenous isointensity mass without necrosis or hemorrhage on T2-weighted image and by enhancement on gadolinium-enhanced study. PMID- 11218018 TI - Imaging of the acute scrotum. AB - The scrotum is a superficial structure and clinical examination is frequently not enough for making a specific diagnosis. In acute scrotal pain US can confirm the presumptive clinical diagnosis and provide additional relevant information. In testicular torsion, color-Doppler imaging has a central role since it has become possible to identify it at early stage by showing absence of perfusion in the affected testis before any gray-scale abnormality. Scintigraphy remains a satisfactory alternative in evaluating testicular torsion and should be used when color Doppler is inadequate, raising doubts about the suspected torsion. Diagnosis of torsion of testicular appendages is particularly difficult. Ischemic infarction shows a characteristic pattern at gray-scale and color Doppler imaging, whereas hemorrhagic ischemia may require MRI. Inflammatory diseases of the scrotum can be easily investigated by echo color Doppler and conventional radiography, and CT can be particularly useful in the detection of gas bubbles. In scrotal trauma, scrotal hematoma, hematocele, intratesticular hematoma, and testicular rupture can be identified using gray-scale US with very good reliability. Magnetic resonance imaging is indicated when a small tear of tunica albuginea is suspected but not visualized on US. PMID- 11218019 TI - The value of endorectal MR imaging to predict positive biopsies in clinically intermediate-risk prostate cancer patients. AB - The aim of this study was to assess the effectiveness of endorectal MR imaging in predicting the positive biopsy results in patients with clinically intermediate risk for prostate cancer. We performed a prospective endorectal MR imaging study with 81 patients at intermediate risk to detect prostate cancer between January 1997 and December 1998. Intermediate risk was defined as: prostatic specific antigen (PSA) levels between 4 and 10 ng/ml or PSA levels in the range of 10-20 ng/ml but negative digital rectal examination (DRE) or PSA levels progressively higher (0.75 ng/ml year(-1)). A transrectal sextant biopsy was performed after the endorectal MR exam, and also of the area of suspicion detected by MR imaging. The accuracies were measured, both singly for MR imaging and combined for PSA level and DRE, by calculating the area index of the receiver operating characteristics (ROC) curve. Cancer was detected in 23 patients (28%). Overall sensitivity and specificity of endorectal MRI was 70 and 76%, respectively. Accuracy was 71% estimated from the area under the ROC curve for the total patient group and 84% for the group of patients with PSA level between 10-20 ng/ml. Positive biopsy rate (PBR) was 63% for the group with PSA 10-20 ng/ml and a positive MR imaging, and 15% with a negative MR exam. The PBR was 43% for the group with PSA 4-10 ng/ml and a positive MR study, and 13% with a negative MR imaging examination. We would have avoided 63% of negative biopsies, while missing 30% of cancers for the total group of patients. Endorectal MR imaging was not a sufficient predictor of positive biopsies for patients clinically at intermediate risk for prostate cancer. Although we should not avoid performing systematic biopsies in patients with endorectal MR imaging negative results, as it will miss a significant number of cancers, selected patients with a PSA levels between 10-20 ng/ml or clinical-biopsy disagreement might benefit from endorectal MR imaging. PMID- 11218020 TI - Endorectal magnetic resonance imaging of prostatic cancer: comparison between fat suppressed T2-weighted fast spin echo and three-dimensional dual-echo, steady state sequences. AB - The aim of this study was to develop an endorectal MRI strategy for prostatic cancer. We evaluated the MR images from 44 consecutive prostatic cancer patients treated by radical prostatectomy. Each sequence from every examination was assessed separately with a specific tumor map drawn. Tumor localization, capsular penetration, and seminal vesicle invasion were marked on maps on the basis of T2 and DESS (dual-echo steady-state) sequences. Thirty patients also had T1-weighted images, and these were assessed with regard to possible tumor outgrowth. The maps were compared with histopathological findings from radical prostatectomy specimens. According to our study, DESS equaled T2 in every respect. No statistically significant differences between the sequences were found with respect to detecting either tumor localization, outgrowth, or seminal vesicle invasion. DESS is a potential new sequence in prostatic MRI as it has been proven to parallel the routinely used T2-weighted imaging. PMID- 11218021 TI - Bilateral papillary renal cell carcinoma. AB - Papillary renal cell carcinoma is a subgroup of malignant renal epithelial neoplasms. We report the clinical and imaging findings of a case with multifocal and bilateral renal cell carcinoma which are nonspecific. PMID- 11218022 TI - Emphysematous cystitis in a patient presenting with paradoxical arterial embolism and intestinal mycobacteriosis without evidence of diabetes. AB - We describe the case of a 72-year-old woman who displayed massive multiple intramural gas collections of the bladder wall as an incidental finding on CT. The patient presented with critical ischemia of the left leg caused by paradoxical arterial embolism, raised corpuscular sedimentation rate, anemia by gastrointestinal blood loss, hypoproteinemia, diarrhea, malabsorption, and exudative enteropathia caused by mycobacterial ileocolitis. The patient had no dysuria and there was no evidence of diabetes. The intramural gas collections of the bladder wall, as shown by CT, were compatible with emphysematous cystitis. Urine samples proved infection by a multi-resistant strain of E. coli. Emphysematous cystitis is a rare form of bladder infection that can be diagnosed by plain-film radiograms or CT. PMID- 11218023 TI - MR features of peripheral nerve sheath tumors: can a calculated index compete with radiologist's experience? AB - The aims of this study were, firstly, to provide a formula (neurogenic index) based on MR characteristics used in daily routine for predicting whether a soft tissue tumor is neurogenic or not, secondly, to test prospectively the performance of this formula, and thirdly, to compare this performance with that of radiologists experienced in MR imaging of soft tissue tumors. Retrospectively, MR images of 70 neurogenic and 70 non-neurogenic soft tissue tumors were evaluated in random order by two teams of two observers each. A neurogenic index (NI) was calculated based on those MR parameters that showed no or minor interobserver variability. Subsequently, three investigators in concert used the NI in a validation group of 15 neurogenic and 22 nonneurogenic soft tissue tumors. The same team, based on their own experience, tried to differentiate in the same validation group neurogenic from non-neurogenic soft tissue tumors. This was expressed in a subjective score (SS). Sensitivity, specificity, and predictive values were calculated. NI comprised spread (intra- or extracompartmental), distribution, fluid-fluid levels, homogeneity on T2-weighted images (WI), highest signal intensity (SI) on T1WI, lowest SI on T2WI, and delineation on T2WI. In the validation group, NI had a sensitivity of 88.6%, a specificity of 52.0%, a positive predictive value (PPV) of 54.1%, and a negative predictive value (NPV) of 84.6% for neurogenic tumors. The subjective score SS was superior and had a sensitivity of 93.3%, a specificity of 77.2%, a PPV of 73.7%, and a NPV of 94.4%. Our NI was less accurate than the SS; however, the low number of false-negative diagnoses for neurogenic tumors warrants continued efforts in development of neural networks. PMID- 11218024 TI - Indirect MR arthrography of the shoulder in detection of rotator cuff ruptures. AB - The aim of this study was to compare the efficacy of indirect MR arthrography images obtained following intravenous contrast injection and conventional MR imaging in the diagnosis of rotator cuff tears. Twenty-four patients with clinically suspected rotator cuff disease were examined. Conventional MR images and post-contrast indirect MR arthrography images were obtained. All images were evaluated in a blinded fashion by two musculoskeletal radiologist. Results were than analyzed depending on surgical output. The correlation coefficient (Spearman rank correlation test) and the kappa values for agreement between surgery and imaging techniques were calculated. The correlation coefficients between indirect MR arthrography and surgery for reader 1 and reader 2 were 0.9137 and 0.9773, respectively. Whereas the agreement between conventional MR imaging and surgery was moderate (n = 0.383-0.571), the agreement between indirect MR arthrography and surgery was excellent (n = 0.873-0.936). We suggest the use of indirect MR arthrography technique when conventional MR images are equivocal in diagnosis of rotator cuff disease. PMID- 11218025 TI - Height of lumbar discs measured from radiographs compared with degeneration and height classified from MR images. AB - The relation between height of lumbar discs (measured from lateral radiographic views) and disc degeneration (classified from MR images) deserves attention in view of the wide, often parallel or interchanged use of both methods. The time sequence of degenerative signs and decrease of disc height is controversial. To clarify the issue, this cross-sectional study documents the relation between disc degeneration and disc height in a selected cohort. Forty-three subjects were selected at random from a cohort examined for potential disc-related disease caused by long-term lifting and carrying. From each subject a lateral radiographic view of the lumbar spine as well as findings from an MR investigation of (in most cases) levels T12/L1 to L5/S1 were available; thus, n = 237 lumbar discs were available for measurement and classification. Disc height was measured from the radiographic views with a new protocol compensating for image distortion and permitting comparison with normal, age- and gender appropriate disc height. Degeneration as well as disc height were classified twice from MR images by independent observers in a blinded fashion. Disc degeneration classified from MR images is not related to a measurable disc height loss in the first stage of degeneration, whereas progressive degeneration goes along with progressive loss of disc height, though with considerable interindividual variation. Loss of disc height classified from MR images is on average compatible with loss of disc height measured from radiographs. In individual discs, however, classification of height loss from MR images is imprecise. The first sign of disc degeneration (a moderate loss of nucleus signal) precedes disc height decrease. As degeneration progresses, disc height decreases. Disc height decrease and progress of degeneration, however, appear to be only loosely correlated. PMID- 11218026 TI - Stress-induced osteolysis of distal clavicle: imaging patterns and treatment using CT-guided injection. AB - Osteolysis of distal clavicle (ODC) may occur in patients who experience repeated stress or microtrauma to the shoulder. This entity has clinical and radiological findings similar to post-traumatic ODC. We describe a case of successful treatment of stress-induced ODC with CT-guided injection of corticosteroid and anesthetic drug into the acromioclavicular joint. PMID- 11218027 TI - Desmoplastic fibroma in the thoracic spine: an unusual localization of a rare primary bone tumor. AB - A case of an intraspinal growing desmoplastic fibroma of the thoracic spine (T9 T11) is reported. Desmoplastic fibroma is a rare tumor of connective tissue that shows a locally infiltrative and destructive growth. An affection of the thoracic spine is an extremely rare manifestation. Preoperative CT documents the extent of osseous destruction and tumor associated cortical erosion. In central tumor areas an inhomogeneous, intermediate to low signal is demonstrated by MRI using T1- and T2-weighted spin-echo and turbo-spin-echo sequences. Contrast-enhanced MRI shows marked enhancement in peripheral areas depicting the extraosseous and intramedullary extension. PMID- 11218028 TI - Percutaneous core-needle biopsy of enlarged lymph nodes in the diagnosis and subclassification of malignant lymphomas. AB - The objective of this study was to evaluate the sensitivity and specificity of percutaneous core-needle biopsy of enlarged lymph nodes in the diagnosis and subclassification of malignant lymphomas. In a 1-year period 158 image-guided percutaneous core-needle biopsies of enlarged lymph nodes were performed on 149 consecutive patients using a Tru-cut needle fired by a biopsy gun. In 135 cases the biopsy findings could be confirmed by histologic examination of additional tissue samples (n = 59) or by correlation with the patient's clinical and radiologic course (n = 76). The final diagnoses were malignant lymphoma in 65 cases, leukemic nodal infiltration in 2, nodal metastases from a solid tumor in 37 and benign changes or no evidence of malignancy in 31 cases. The core-needle biopsies correctly diagnosed 58 of 65 malignant lymphomas, corresponding to a sensitivity of 89% and a specificity of 97%. Fifty-five of the 58 (95%) correctly diagnosed malignant lymphomas could be subclassified on the basis of the core needle biopsy. Image-guided core-needle biopsy of enlarged lymph nodes with a Tru cut needle is a useful method for the diagnosis and subclassification of malignant lymphomas. PMID- 11218029 TI - DIMA enlargement mammography in microcalcifications: a prospective study with ROC analysis. AB - The purpose of this study was to investigate whether the four-fold magnification mammography (direct magnification, DIMA) technique would perform better than conventional 1.5-fold magnification mammography in the differentiation of breast microcalcifications into benign and malignant. Fifty patients with non-palpable microcalcifications detected by mammography were examined immediately prior to surgical biopsy using both a conventional (1.5-fold) and the DIMA (fourfold) magnification mammography techniques. The microcalcifications were classified by five experienced radiologists using morphological criteria. A receiver operating characteristics curve (ROC) analysis of the sensitivity and specificity of both techniques in assessing malignancy was then carried out. The DIMA mammography technique was slightly but non-significantly superior to the conventional method in detecting malignancy (p > 0.05). Coarse granular and pleomorphic calcifications were detected more frequently with the DIMA technique. Coarse calcifications were significantly more frequently associated with histologically benign findings, whereas fine granular calcifications were significantly more likely to be malignant lesions. Assessment of malignancy associated with microcalcifications using morphological criteria is not significantly improved by mammography techniques with higher magnification. PMID- 11218030 TI - A cavernous haemangioma of breast in male: radiological-pathological correlation. AB - Vascular tumours of the breast are especially rare in men, and a majority of them are angiosarcomas. In fact, we found only four cases of haemangioma in males in the literature. We present a case of cavernous haemangioma in a male aged 48 years, and which commenced as a palpable mass. We performed differential diagnosis and radiological-pathological correlation. We established the correct classification of this case histologically, and decided on the definitive therapeutic approach. PMID- 11218031 TI - Preliminary experience with dynamic MR projection angiography in the evaluation of cervicocranial steno-occlusive disease. AB - The application of a contrast-enhanced, two-dimensional MR technique, which provides dynamic projection angiograms at a subsecond temporal frame rate for depiction of the cervical and intracranial arteries, was evaluated in three healthy volunteers and seven patients with various cervicocranial steno-occlusive diseases. Intra-arterial digital subtraction angiography (DSA) served as standard of reference for findings in the patients. Magnetic resonance projection angiography (MRPA) was performed on a standard 1.5-T clinical MR imaging system at intravenous injection of a single dose of contrast agent (0.1 mmol/kg GdDTPA BMA). Sixty consecutive images of the cerebral circulation were acquired at a temporal frame rate of 900 ms per image in the coronal plane. The collateral flow and the perfusion of the compromised vessel territory were readily assessed by MPRA in patients with occlusion of the internal cerebral artery (ICA) or middle cerebral artery (MCA). The leptomeningeal collateralisation of these patients was displayed in a dynamic fashion. Furthermore, quantitative perfusion measurement provided a difference between both MCA territories in the time to peak (deltaDTTP) of the contrast bolus of 1.12 +/- 0.28 s in five patients with severe stenosis or occlusion of the ICA (healthy volunteers 0.19 +/- 0.05 s). However, important pathological findings, such as the evaluation of carotid artery stenoses and the intracranial collateral flow pattern in patients with severe carotid stenoses, were not sufficiently assessable as compared with DSA. We conclude that the possibility of obtaining simultaneously information about morphology and perfusion dynamics of the cervicocranial vessels is unique in MPRA as compared with other MR techniques. However, in the applied form, the technique is not a reliable tool for the complete evaluation of the cervicocranial vessels in patients with steno-occlusive disease. PMID- 11218032 TI - Fluid-attenuated inversion-recovery MR imaging of gliomatosis cerebri. AB - Magnetic resonance imaging has been shown to be the most sensitive imaging modality in the assessment of gliomatosis cerebri. Recent studies have shown that fluid-attenuated inversion-recovery (FLAIR) is a valuable MR sequence in the delineation of cerebral pathologies including intra-axial tumors. However, no data are available about the role of this novel technique in the assessment of gliomatosis lesions. The purpose of this study was therefore to evaluate the diagnostic potential of FLAIR MR imaging in patients with suspected gliomatosis cerebri. Seven patients suspected of having lesions of gliomatosis cerebri were examined by T1-weighted spin echo (SE), T2-weighted fast spin echo (FSE), and FLAIR MR imaging with identical slice parameters. T1 and FLAIR were repeated after contrast media administration. Delineation and extent of gliomatosis were the primary parameters of the image analysis. The FLAIR imaging clearly delineated the extent of gliomatosis lesions in all patients. Due to the suppression of cerebrospinal fluid, the delineation was superior to conventional T2-weighted FSE images. Especially the detection and delineation of cortical spread and the infiltration of the corpus callosum was best seen on FLAIR images. The FLAIR MR imaging is a valuable diagnostic modality in the assessment of patients with gliomatosis cerebri. Due to its better delineation of tumor spread, it was found to be the imaging method of choice and should therefore be integrated into the MR imaging protocol of these patients. PMID- 11218033 TI - CT and MRI findings in gliomatosis cerebri: a neuroradiologic and neuropathologic review of diffuse infiltrating brain neoplasms. AB - The aim of the study was to develop objective criteria that might be helpful for the diagnosis of gliomatosis cerebri (GC) with the highest possible probability based on both the neuroradiological and histopathological findings. Imaging findings in 14 patients with diffuse infiltrating brain neoplasms were studied by two neuroradiologists. Computed tomography and MRI scans were compared with each other side by side. The extent and kind of disease were graded on a scale of 1-5. Interexamination agreement between the two methods was calculated using a kappa analysis. Neither of the neuroradiologists performed the examinations and both were blinded to the histopathological findings, which were also available for all patients, based on biopsy as well as follow-up CT and MRI studies. A neuroradiological-neuropathological correlation was performed. A score system helped to differentiate the findings in three categories: 1 = suggestive of GC; 2 = GC cannot be excluded; and 3 = others. Both CT and MRI were performed in 14 patients with clinical signs and symptoms of an intracerebral tumor. All examinations had diagnostic quality and showed the involvement of at least two brain lobes. Stereotactic biopsy was carried out in all patients. In 2 patients the neuropathological diagnosis was suggestive of GC, in 1 patient glioblastoma, in 2 patients astrocytoma, and in 5 patients nonspecific astrogliotic proliferation. In the remaining 4 cases anaplastic tumor infiltration was diagnosed. The neuroradiological findings in 5 cases were suggestive of GC; in 6 cases a GC could not excluded; and in 3 patients only a slight probability of GC was found. In 2 cases was the neuropathological and the neuroradiological diagnosis of GC concordant. Magnetic resonance imaging is significantly more sensitive than CT in the diagnosis of GC. However, even with multiple, MRI-guided stereotactic biopsies in correlation with intraoperative analysis of the sample by smear preparations by a neuropathologist the antemortem diagnosis of GC is still difficult. Discussion of neuropathological and neuroradiological findings in each case in combination with a score system may help to resolve discrepancies. PMID- 11218035 TI - MRI of the brachial plexus. AB - Magnetic resonance imaging is the imaging method of first choice for evaluating the anatomy and pathology of the brachial plexus. This review discusses the used imaging techniques, the normal anatomy, and a variety of pathologies that can involve the brachial plexus. The pathology includes primary and secondary tumors (the most frequent secondary tumors being superior sulcus tumor and metastatic breast carcinoma), radiation plexopathy, trauma, thoracic outlet syndrome, neuralgic amyotrophy, chronic inflammatory demyelinating polyneuropathy (CIDP), and multifocal motor neuropathy (MMN). PMID- 11218034 TI - Temporal lobe changes following radiation therapy: imaging and proton MR spectroscopic findings. AB - Radiation therapy for nasopharyngeal carcinoma affects the temporal lobes. This paper characterizes proton MR spectroscopic findings of the temporal lobes and correlates them with imaging changes. Single-voxel proton MR spectroscopic examinations were acquired from 13 healthy adult volunteers (25 spectra) and 18 patients (28 spectra). All patients had biopsy-confirmed nasopharyngeal carcinoma and were previously treated with radiation therapy. Six patients (33%) had a single treatment and 12 (67%) patients had two treatments. Point resolved spectroscopy (PRESS) method was used (TR = 3,000 ms, TE = 135 ms) and data processed automatically using the LCModel software package for metabolite quantification. Voxel size and geometry were adapted to the lesion to reduce skull-base lipid contamination. The metabolites were quantitated relative to water signal. For each location, an additional non-water-suppressed reference scan in fully relaxed conditions was performed. The imaging findings were divided into four categories: I, normal; II, edema only; III, contrast-enhancing lesions; and IV, cystic encephalomalacia. The N-acetyl-aspartate levels were reduced in 27 (96%) spectra. Choline was increased in 3 (11%), normal in 4 (14%), and reduced in 21 (75%) spectra. The creatine level was normal in 8 (29%) spectra and reduced in 20 (71%) spectra. Imaging showed 4 (14%) spectra with category-I imaging findings; 5 (18%) spectra with category-II findings; 15 (54%) spectra with category-III findings; and 4 (14%) spectra with category-IV findings. Magnetic resonance spectroscopy showed reduced N-acetyl-aspartate in radiation-induced temporal lobe changes. Creatine levels were relatively more stable. Choline levels may be increased, normal, or reduced. Imaging findings ranged from normal to contrast-enhancing lesions and cystic encephalomalacia. PMID- 11218036 TI - Networks in the radiology department and the hospital. AB - Data networks are a basic technology with regard to an appropriate design of the information technology (IT) infrastructure for the hospital. Due to the distributed workflow within the hospital, an integrated Hospital Information System (HIS) is based mostly on a set of network applications facing specific items. Medical communication standards, i.e., HL 7, DICOM, and in the near future the migration towards XML, support the interoperability between the IT subsystems and pave the way to patient information systems with access to unified and complete electronic medical records (EMR). Furthermore, with standardized communication techniques, such as CORBAmed, an object-oriented design of Healthcare applications will be possible in the near future. The intent of this paper is to give an overview of which basic technologies are suitable for building comprehensive, flexible, and reliable hospital networks and which also meet the special demands of the radiology department. PMID- 11218037 TI - Angiographic pseudolesion in the liver in asymptomatic subacute cholecystitis. PMID- 11218038 TI - Antrochoanal polyps in children. PMID- 11218039 TI - Intralobar lung sequestration and surrounding hyperaeration. PMID- 11218040 TI - Quiz case of the month. Partially thrombosed aneurysm of the extracranial carotid artery. PMID- 11218041 TI - Comparative assessment of endocrine modulators with oestrogenic activity: I. Definition of a hygiene-based margin of safety (HBMOS) for xeno-oestrogens against the background of European developments. AB - A novel concept - the hygiene-based margin of safety (HBMOS) - is suggested for the assessment of the impact of potential endocrine modulators. It integrates exposure scenarios and potency data for industrial chemicals and naturally occurring dietary compounds with oestrogenic activity. An HBMOS is defined as a quotient of estimated daily intakes weighted by the relative in vivo potencies of these compounds. The Existing Chemicals Programme of the European Union provides Human and Environmental Risk Assessments of Existing Chemicals which include human exposure scenarios. Such exposure scenarios, along with potency estimates for endocrine activities, may provide a basis for a quantitative comparison of the potential endocrine-modulating effects of industrial chemicals with endocrine modulators as natural constituents of human diet. Natural phyto-oestrogens exhibit oestrogenic activity in vitro and in vivo. Important phyto-oestrogens for humans are isoflavones (daidzein, genistein) and lignans, with the highest quantities found in soybeans and flaxseed, respectively. Daily isoflavone exposures calculated for infants on soy-based formulae were in the ranges of 4.5 8 mg/kg body wt.; estimates for adults range up to 1 mg/kg body wt. The Senate Commission on the Evaluation of Food Safety (SKLM) of the Deutsche Forschungsgemeinschaft has also indicated a wide range of dietary exposures. For matters of risk assessment, the SKLM has based recommendations on dietary exposure scenarios, implying a daily intake of phyto-oestrogens in the order of 1 mg/kg body wt. On the basis of information compiled within the Existing Chemicals Programme of the EU, it appears that a daily human exposure to nonylphenol of 2 microg/kg body wt. may be a worst-case assumption, but which is based on valid scenarios. The intake of octylphenol is much lower, due to a different use pattern and applications, and may be neglected. Data from migration studies led to estimations of the daily human uptake of bisphenol A of maximally 1 microg/kg body wt. On the basis of comparative data from uterotrophic assays in rats, with three consecutive days of oral applications involved, and taking the natural phyto-oestrogen daidzein as reference (= 1), relative uterotrophic activities in DA/Han rats follow the sequence: daidzein = 1; bisphenol A = 1; p-tertoctylphenol = 2; o, p'-DDT = 4; ethinyl oestradiol = 40,000. The derived values from exposure scenarios, as well as these relative potency values and bridging assumptions, led to calculations of HBMOS as a quantitative comparison of potential endocrine modulating effects of industrial chemicals with those of natural constituents of human diet. HBMOS estimates for nonylphenol ranged between 250 and 500, dependent on bridging assumptions, and around 1000 for bisphenol A. The derivations of HBMOS were in full support of the conclusions reached by the SKLM of the Deutsche Forschungsgemeinschaft. The estimated HBMOS values for the industrial chemicals (nonylphenol, bisphenol A) appear sufficiently high to ensure the absence of a practical risk to human health under the present exposure conditions. PMID- 11218042 TI - The relevance of physical activity for the kinetics of inhaled gaseous substances. AB - Inhalation is the most important route of absorption for many volatile substances. The inhaled chemical is distributed via the bloodstream into the organs and tissues. It is eliminated mainly unchanged by exhalation and also via metabolism. The blood concentration can be considered as a surrogate for the body burden of the chemical. It depends on the rate of uptake and on the rate of elimination. The rate of uptake by inhalation is determined by the blood:air partition coefficient of the gaseous compound, the actual concentration of the chemical already in the blood entering the lungs, the blood flow through the lungs, and the alveolar ventilation. The latter is greatly influenced by physical activity, which thus has a crucial impact on the rate of uptake. Consequently, the blood concentration of an inhaled chemical and the resulting alveolar retention, representing the rate of metabolism at steady-state, are dependent on the intensity of physical work. Both parameters can be calculated for steady state conditions using simple algebraic equations, if one assumes that the rate of metabolic elimination is limited by the blood flow through the metabolizing organs. This assumption is valid for many rapidly metabolized inhaled gases and vapours at low concentrations present under workplace conditions. The derived equations give the theoretical background for the observations presented from a series of experimental studies which demonstrate that physical activity can be a major determinant of the toxicokinetics of inhaled compounds. Practical examples illustrate the procedure. We conclude that workplace-related physical activity should be taken into account for compounds with blood:air partition coefficients above 6 in the determination of occupational limit concentrations in air. PMID- 11218043 TI - The disposition and metabolism of durene (1,2,4,5-tetramethylbenzene) in rats. AB - The organ and tissue distribution, excretion and metabolism of [3H]1,2,4,5 tetramethylbenzene ([3H]durene) in male Wistar albino rats were investigated following a single i.p. administration (40 mg/kg) and within 9 days after five daily repeated administrations. Urine proved to be the main route of tritium excretion. Within the first 24 h after a single administration 69% of the radioactivity was excreted in the urine and only 9% in the feces. The highest level of tritium binding was found in the fat tissue, liver, kidneys and adrenal glands. The accumulation of tritium in the plasma proceeded with a kinetic constant of 0.49 h(-1), whereas the half-life of radioactivity decay amounted to about 6.3 h. In erythrocytes, the tritium level was found to be about three times lower than in blood plasma. The total amount eliminated during the 9 days following repeated administration was about 94% of the five doses given. The highest level of tritium was found in fat tissue and adrenal glands, followed by the liver, kidneys, sciatic nerve and muscle. A gradual decline in tritium levels was observed during the following 4 days in most tissues to reach about 2% of the dose given. The main urinary metabolites resulting from the administration of durene were 2,4,5-trimethylbenzyl alcohol (about 22%), 4,5-dimethyl-1,2 benzdialdehyde (about 19%), 2,4,5-trimethylbenzaldehyde (about 19%) and 2,4,5 trimethylbenzoic acid (about 16%). The oxygen-containing metabolites accounted for almost 80%, whereas sulphur-containing metabolites accounted for approximately 10% of the products of biotransformation. In conclusion, most of the durene administered has a relatively rapid turnover rate, with minor levels retained in the tissues for longer time periods. PMID- 11218044 TI - Hemoglobin adducts of epoxybutene in workers occupationally exposed to 1,3 butadiene. AB - 1,3-Butadiene (BD) is an important chemical widely used in the synthetic rubber industry. Hemoglobin adducts of two of its reactive metabolites have been already investigated as possible parameters for exposure assessment. In this study hemoglobin adducts of epoxybutene (EB) were analyzed in blood samples from 17 workers in a BD monomer production unit and 19 controls in a heat production unit of a petrochemical plant near Prague, Czech Republic. BD exposure was determined by personal air sampling. The median level of exposure was 440 microg/m3 (range < 11-17 mg/m3) for the exposed workers and < 6 microg/m3 (< 5-150 microg/m3) for the controls. The adduct N-(2-hydroxy-3-butenyl)valine (HBVal) formed by the reaction of the N-terminal valine of globin with carbon-1 of EB was measured. The N-alkylated amino acid was analyzed by gas chromatography/mass spectrometry (GC/MS) after degradation by the modified Edman procedure. Using published methods problems arose with high background levels, especially in the negative ion chemical ionization (NCI) mode. In the present study a limit of detection of 0.2 pmol/g globin was achieved by using 400 mg globin, a variation in extraction solvents, an additional purification step and a widely extended GC temperature program. The median hemoglobin adduct level of the Czech BD monomer production workers (0.7 pmol/g globin; n = 17) was significantly higher than that of the controls (0.2 pmol/g globin; n = 19; P<0.05). Smoking controls showed higher hemoglobin adduct levels than nonsmoking controls (P<0.1) and significantly higher BD exposure levels (P<0.01). PMID- 11218045 TI - Glutathione transferase activities in renal carcinomas and adjacent normal renal tissues: factors influencing renal carcinogenesis induced by xenobiotics. AB - In general, the biological activation of nephrocarcinogenic chlorinated hydrocarbons proceeds via conjugation with glutathione. It has mostly been assumed that the main site of initial conjugation is the liver, followed by a mandatory transfer of intermediates to the kidney. It was therefore of interest to study the enzyme activities of subgroups of glutathione transferases (GSTs) in renal cancers and the surrounding normal renal tissues of the same individuals (n = 21). For genotyping the individuals with respect to known polymorphic GST isozymes the following substrates with differential specificity were used: 1 chloro-2,4-dinitrobenzene for overall GST activity (except GST theta); 7-chloro-4 nitrobenzo-2-oxa- 1,3-diazole for GST alpha; 1,2-dichloro-4-nitro-benzene for GST mu; ethacrynic acid and 4-vinylpyridine for GST pi; and methyl chloride for GST theta. In general, the normal tissues were able to metabolize the test substrates. A general decrease in individual GST enzyme activities was apparent in the course of cancerization, and in some (exceptional) cases individual activities, expressed in the normal renal tissue, were lost in the tumour tissue. The GST enzyme activities in tumours were independent of tumour stage, or the age and gender of the patients. There was little influence of known polymorphisms of GSTM1, GSTM3 and GSTP1 upon the activities towards the test substrates, whereas the influence of GSTT1 polymorphism on the activity towads methyl chloride was straightforward. In general, the present findings support the concept that the initial GST-dependent bioactivation step of nephrocarcinogenic chlorinated hydrocarbons may take place in the kidney itself. This should be a consideration in toxicokinetic modelling. PMID- 11218046 TI - Evidence against a major role of plasmalogens in the resistance of astrocytes in lactic acid-induced oxidative stress in vitro. AB - Astrocytes are known to play a key role in buffering extracellular pH variations and, in addition, they are particularly resistant to oxidative stress and subsequent lipid peroxidation. This great resistance may be ascribed to the presence of high concentrations of certain antioxidants, but another explanation may be the presence of a high quantity of plasmalogens, which are a special group of glycerophospholipids characterized by a vinyl ether bond instead of an ester bond in the sn-1 position of the glycerol backbone. Plasmalogens are sensitive to free radical attack and acidity, and numerous works have supported the hypothesis that they may be antioxidant molecules that protect cells from oxidative stress. The aim of this work was to investigate, on astrocytes in lactic acid-induced oxidative stress (pH 5.5), the behavior of phospholipids and, in particular, plasmalogens. Two main techniques, based on the susceptibility of the vinyl ether bond to hydrolysis, were employed in this study to measure plasmalogen levels. In both cases, the sn-1 vinyl ether linkage was cleaved using mercuric chloride, producing a lysophospholipid that was assessed by phosphorus measurement or using HCl treatment, producing a long-chain fatty aldehyde assayed by gas chromatography/mass spectrometry. On astrocytes in culture, only plasmenylethanolamine (PlmEtn) was evidenced, representing 40% of glycerophosphoethanolamine lipids. When astrocytes were incubated with lactic acid, no modification in the amount of PlmEtn was seen. Furthermore, free aldehydes and aldehydes corresponding to the quantity of intact plasmalogens were similar to those observed on controls. In addition, the constancy of two lipid peroxidation markers, thiobarbituric acid reactive substances and polyunsaturated fatty acids, was clear evidence of the resistance of these cells in lactic acid conditions. In conclusion, our results fail to demonstrate a major role of plasmalogens in the resistance of astrocytes in lactic acid-induced oxidative stress. PMID- 11218047 TI - On the interactions between antimuscarinic atropine and NMDA receptor antagonists in anticholinesterase-treated mice. AB - Both organophosphate (OP) and carbamate pesticides may produce seizures and death commonly attributed to the inhibition of acetylcholinesterase (AChE) and subsequent excess of acetylcholine (ACh). The anticonvulsant and neuroprotective properties of N-methyl-D-aspartate (NMDA) receptor antagonists in animals encouraged us to investigate their effects on the toxic and convulsant properties of OP and carbamate pesticides. Adult Swiss mice were systemically injected with the OP pesticide, chlorfenvinphos (CVP), or the carbamate pesticide, methomyl (MET). Both CVP and MET induced dose-dependent seizure activity and death in mice. Pretreatment with the muscarinic antagonist, atropine (ATR), at a dose of 1.8 mg/kg did not prevent seizures but decreased the lethal effects of CVP and MET. Pretreatment with the NMDA antagonists, dizocilpine (MK-801) at a dose of 1 mg/kg or 3-((R,S)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) at a dose of 10 mg/kg, influenced neither MET-induced seizures nor CVP- or MET-induced death. However, both MK-801 and CPP blocked CVP-induced seizures. Concurrent administration of ATR and the NMDA antagonists prevented seizures produced by CVP, but not those produced by MET. Nevertheless, both MK801 and CPP coadministered with ATR markedly enhanced its antilethal effects in CVP- and MET intoxicated mice. The antidotes had no influence upon brain AChE activities in mice treated with saline or CVP or MET. It seems that combined treatment with ATR and NMDA receptor antagonists might be of clinical relevance. PMID- 11218048 TI - Differential response of immature rat uterine tissue to ethinylestradiol and the red wine constituent resveratrol. AB - The stilbene derivative resveratrol (RES) is a phytoalexin of grapes, peanuts and other fruits. It is structurally related to stilbene estrogens and an estrogenic potential of RES has recently been demonstrated in a number of in vitro studies. In this investigation, the uterotrophic responses of immature Wistar rats to subcutaneous administration of RES (18, 58, and 575 mg/ kg) and the reference estrogen ethinylestradiol (EE2; 0.3, 1, 3, 30 microg/kg) on three consecutive days were determined. Uterine weight, histopathological changes, immunohistochemical expression of nuclear estrogen receptor-alpha (ERalpha) and progesterone receptor (PR) protein, gene expression of ERalpha and PR at the messenger ribonucleic acid (mRNA) level and peroxidase induction were examined. EE2 dose dependently increased uterine weight, enlarged the uterine lumen and induced hypertrophy of epithelial, stromal and myometrial cells. Expression of ERalpha protein in epithelial, stromal and myometrial nuclei and of PR protein in epithelial nuclei was reduced in EE2-treated rats, while PR protein in stromal and myometrial nuclei was increased in a dose-dependent manner. EE2 increased messenger ribonucleic acid (mRNA) levels of uterine PR and induced peroxidase activity. In contrast, RES rather mildly decreased uterine weight, while histology did not reveal differences between controls and RES-treated rats. Expression of nuclear ERalpha protein was dose dependently decreased in epithelial, stromal and myometrial cells of RES-treated rats, while nuclear PR protein content was similar in controls and RES-treated rats. Following administration of RES, a trend toward reduced levels of ERalpha and PR mRNA was found, while no peroxidase induction occurred. Plasma levels of RES, 45 min after the administration of a single subcutaneous dose of 500 mg/kg, were in the range 1-2 microM. In summary, an estrogenic potential of RES could not be substantiated in this in vivo study, although the most effective route of administration and extremely high doses were used and plasma levels were in the range reported to be effective in vitro. Whether other pharmacological properties of RES could mediate the observed changes in RES-treated animals is discussed. PMID- 11218049 TI - Evidence of a no-effect level in silica-induced rat lung mutagenicity but not in fibrogenicity. AB - Exposure to silica can lead to fibrosis and the development of lung tumors in the rat. Based on these animal studies and on epidemiological data, silica has been classified as a human carcinogen. The initial mechanisms have not been finally clarified, but particle-induced tumor formation is at least closely associated with inflammation, the production of reactive oxygen species (ROS) and DNA damage. We investigated the dose-dependent effects of silica on the formation of the major DNA oxidation product 8-oxoguanine (8-oxo-Gua) in rat lung cells, on p53 (p53) and p53 mutant protein (p53 mut) synthesis, as well as on the amount of the surfactant phospholipids phosphatidylinositol (PI) and phosphatidylglycerol (PG) in the bronchoalveolar lavage fluids (BALF) as indicators of fibrotic processes in the lung. Rats were exposed by intratracheal instillation to various amounts of DQ12 quartz (0.15, 0.3, 0.6, 1.2, 2.4 mg/animal) and lungs were investigated after 21 and 90 days. PG decreased and PI increased quartz dose dependently. 8-oxoGua was significantly increased only after 1.2 and 2.4 mg quartz/animal. Cells expressing p53 protein were increased at 1.2 and 2.4 mg, p53 mutant protein only at 2.4 mg/animal. This indicates a no-effect level for mutagenicity at a low, but still fibrogenic quartz exposure. PMID- 11218050 TI - Formation of DNA adducts from oil-derived products analyzed by 32P-HPLC. AB - The aim of this study was to investigate the genotoxic potential of DNA adducts and to compare DNA adduct levels and patterns in petroleum vacuum distillates, coal tar distillate, bitumen fume condensates, and related substances that have a wide range of boiling temperatures. An in vitro assay was used for DNA adduct analysis with human and rat S-9 liver extract metabolic activation followed by 32P-postlabeling and 32P-high-performance liquid chromatography (32p-HPLC). For petroleum distillates originating from one crude oil there was a correlation between in vitro DNA adduct formation and mutagenic index, which showed an increase with a distillation temperature of 250 degrees C and a peak around a distillation point of approximately 400 degrees C. At higher temperatures, the genotoxicity (DNA adducts and mutagenicity) rapidly declined to very low levels. Different petroleum products showed a more than 100-fold range in DNA adduct formation, with severely hydrotreated base oil and bitumen fume condensates being lowest. Coal tar distillates showed ten times higher levels of DNA adduct formation than the most potent petroleum distillate. A clustered DNA adduct pattern was seen over a wide distillation range after metabolic activation with liver extracts of rat or human origin. These clusters were eluted in a region where alkylated aromatic hydrocarbons could be expected. The DNA adduct patterns were similar for base oil and bitumen fume condensates, whereas coal tar distillates had a wider retention time range of the DNA adducts formed. Reference substances were tested in the same in vitro assay. Two- and three-ringed nonalkylated aromatics were rather low in genotoxicity, but some of the three- to four-ringed alkylated aromatics were very potent inducers of DNA adducts. Compounds with an amino functional group showed a 270-fold higher level of DNA adduct formation than the same structures with a nitro functional group. The most potent DNA adduct inducers of the 16 substances tested were, in increasing order, 9,10-dimethylanthracene, 7,12-dimethylbenz[a]anthracene and 9-vinylanthracene. Metabolic activation with human and rat liver extracts gave rise to the same DNA adduct clusters. When bioactivation with material from different human individuals was used, there was a significant correlation between the CYP 1A1 activity and the capacity to form DNA adducts. This pattern was also confirmed using the CYP 1A1 inhibitor ellipticine. The 32P-HPLC method was shown to be sensitive and reproducible, and it had the capacity to separate DNA adduct forming substances when applied to a great variety of petroleum products. PMID- 11218051 TI - Topiramate in childhood epilepsy: past, present, and future. PMID- 11218052 TI - Topiramate in the catastrophic epilepsies of childhood. AB - Several epileptic syndromes that occur during childhood are characterized by severe treatment-resistant seizures, progressive loss of higher intellectual functions, and characteristic electroencephalographic abnormalities. These catastrophic epileptic syndromes include epileptic encephalopathy with diffuse slow spike waves (Lennox-Gastaut syndrome), West syndrome, progressive myoclonic epilepsies, and electrical status epilepticus during sleep. This article summarizes each syndrome and reviews the most recent information concerning the effectiveness of topiramate with respect to each condition. Suggestions are offered to help clinicians maximize topiramate's efficacy and tolerability in patients suffering with these syndromes. Overall, topiramate is a valuable antiepileptic medication in the treatment of catastrophic pediatric epileptic syndromes. PMID- 11218053 TI - Safety and tolerability of topiramate in children. AB - Three double-blind, randomized, placebo-controlled studies of topiramate that include children have been published and prospective but unblinded and retrospective reviews have been reported providing information regarding topiramate's safety and tolerability. These studies indicate that side effects tend to occur early in treatment with topiramate, especially in children receiving polypharmacy. Two classes of adverse events are commonly reported: central nervous system and anorexia/weight loss. Central nervous system effects include somnolence, difficulties with concentration, and behavior changes. Tolerance to these effects seems to develop in most children. When it occurs, weight loss has been noted in the first 12 to 18 months, after which normal weight gain resumes, without long-term impact on growth. As opposed to the experience in adults, aphasia and word-finding difficulties are not commonly seen, and parasthesiae are not reported by children. Renal calculi are rare. Life threatening idiosyncratic reactions have not been attributed to topiramate. While metabolic acidosis has been reported, no other clinically significant laboratory abnormalities have been associated with the use of topiramate in children. PMID- 11218054 TI - Pharmacokinetics and pharmacodynamics of topiramate. AB - In the treatment of children with epilepsy, the role of topiramate has been expanding gradually. The main factor that has contributed to this trend is the relatively large body of information that has accumulated on the clinical pharmacology of topiramate in children, including its broad-spectrum efficacy, pediatric pharmacokinetics, side-effect profile, and safety. It has also become increasingly apparent with time that topiramate, in contrast to other broad spectrum antiepileptic drugs used in children, does not seem to be associated with a significant risk of any serious or life-threatening adverse effects. The present review summarizes the available evidence related to the clinical pharmacology of topiramate in children and provides an update on its known mechanisms of action. Finally, available experimental data on the neuroprotective effect of topiramate are reviewed because of their considerable clinical potential in the treatment of children and newborns. PMID- 11218055 TI - Use of topiramate in localization-related epilepsy in children. AB - Topiramate has been shown to be safe and effective in refractory partial epilepsy in children. Pharmacokinetic studies show that the clearance of topiramate is greater in children than in adults; therefore, higher doses may be needed in children than adults. It is generally well tolerated, except for cognitive dysfunction. Weight loss and the risk of renal stones can be significant in some cases. However, when compared with other anticonvulsant medications, topiramate has few serious idiosyncratic reactions such as rash, hematologic reactions, and hepatotoxicity. PMID- 11218056 TI - Use of topiramate in childhood generalized seizure disorders. AB - Topiramate is a sulfamate derivative of the naturally occurring monosaccharide D fructose. It was initially approved in the United States as adjunctive therapy for partial seizures in 1997. However, there is increasing evidence that it is effective in the treatment of generalized seizures and epilepsy syndromes. Initially, open-label studies using topiramate as add-on therapy in children with refractory generalized seizure types were performed. These showed improvement in patients with the following generalized seizure types: typical and atypical absence, atonic, myoclonic, generalized tonic-clonic, and juvenile myoclonic epilepsy. Double-blind, placebo-controlled multicentered studies in patients with refractory primary generalized tonic-clonic seizures and epilepsy syndromes were performed. The median reduction in seizure frequency for primary generalized tonic-clonic seizures was 56.7% for topiramate and 9% for placebo. Additionally, 13.6% of topiramate-treated patients were primary generalized tonic-clonic seizure free for the study period. In the topiramate-treated juvenile myoclonic epilepsy patients, primary generalized tonic-clonic seizures were reduced > 50% in 73% of patients. Open-label extension showed that primary generalized tonic clonic seizures were reduced >50% in 63% of topiramate-treated patients for > or = 6 months, and 16% were primary generalized tonic-clonic seizure free > or = 6 months. Accumulating evidence suggests that topiramate has a broad spectrum of antiepileptic effect. Moreover, life-threatening organ toxicity has not been attributed to topiramate. Topiramate is an effective treatment for refractory generalized seizure types and epilepsy syndromes encountered in children. PMID- 11218057 TI - Parvalbumin and GABA in the developing somatosensory thalamus of the rat: an immunocytochemical ultrastructural correlation. AB - The calcium binding protein parvalbumin (PV) is widely distributed in the mammalian nervous system and its relationship with GABAergic neurons differs within thalamic nuclei and animal species. In the rat somatosensory thalamus PV immunoreactive (ir) neurons were found only in the GABAergic reticular thalamic nucleus (RT), while a dense PVir neuropil is present in the ventrobasal complex (VB). In this study the distribution and relationship of PV and GABA were investigated in RT and VB during postnatal development at electron microscopic level. The pre-embedding immunoperoxidase detection of PV was combined with the post-embedding immunogold localization of GABA. In RT, at all developmental ages, neuronal cell bodies, dendrites and rare axonal terminals were both PVir and GABAir. In VB during the first postnatal week several small vesicle-containing profiles were double-labelled and some of them were identifiable as synaptic terminals. From postnatal day 7 (P7) to P9 the medial part of VB was more intensely PVir than the lateral one and some differences in the sequence of maturation of PVir terminals were noted between these two VB subdivisions. Single labelled PVir profiles were first observed at P8, whereas single-labelled PVir terminals appeared at P12 and at P15 they became more frequent and larger, showing the typical morphology of ascending afferents described in adult VB. These results demonstrate the late expression of PV and acquisition of adult morphology in ascending terminals of rat VB during postnatal development in comparison with the innervation arising from the GABAergic RT. PMID- 11218058 TI - The distribution of NPY-like immunoreactivity in the chameleon brain. AB - The distribution of neuropeptide Y (NPY) immunoreactivity was studied in the brain of the chameleon. Cell bodies and fibers displaying NPY-like immunoreactivity were widely dispersed throughout the brain and at the highest density in the telencephalon and diencephalon. Immunolabeled cell bodies were numerous in the medial and dorsomedial cortex and in the dorsal ventricular ridge, while the striatum and basal telencephalon only contained sparsely scattered NPY-positive somata. Immunopositive neurons were densely distributed in the dorsal thalamus (particularly in the perirotundal belt), the area triangularis, the nucleus geniculatus lateralis pars dorsalis, the periventricular hypothalamus and the medial eminence. In the pretectum, NPY immunoreactive cell bodies were limited to the nucleus posterodorsalis, while in the mesencephalon immunolabeled somata were found in the stratum album centrale of the optic tectum and in the substantia nigra. Immunopositive fibers and terminals were particularly dense in the dorsomedial cortex, the periventricular hypothalamus, the nuclei accumbens, suprachiasmaticus and griseus tectalis, in the substantia nigra and in the torus semicircularis. These findings show that the NPY system in the chameleon has the same basic organization as in other vertebrate species, and indicate that this peptide could be also implicated in the regulation of several aspects of cerebral functions. In addition, and of particular interest, is the observation of numerous NPY-immunoreactive neurons and fibers in several visual nuclei, suggesting an important involvement of this substance in the visual function. PMID- 11218059 TI - Changing synaptic connections on cell bodies of growing identified spinal motoneurons of the eel, Anguilla. AB - As the target musculature they innervate grows throughout life, certain segmental motoneurons from the spinal cord of Anguilla, readily identified on the basis of their form and position, also increase in size. In doing so, they present a steadily increasing target to the spinal and supraspinal neurons that innervate them. How the afferent neurons respond was assessed by measuring features of their synaptic boutons contacting the motoneuronal perikarya, as seen with electron microscopy. About 60% of the perimeter of the perikaryal profile of each motoneuron was found to be covered with synaptic bouton profiles, a value that is independent of the size of the motoneuron. Furthermore, the distances between synaptic profiles, their contact sizes (measured as apposition length) and the number and size of the vesicles each profile contains were all found to be relatively constant and also independent of motoneuronal size. In contrast, the number of synaptic profiles contacting a motoneuron correlated well with its perikaryal size. Our findings indicate that the challenge of a growing neuronal target is met by a steady increase in the number of contacting boutons, the form and spacing of which are held relatively constant; this strategy will require continual synaptic realignment at the target. PMID- 11218060 TI - The apical ectodermal ridge, fibroblast growth factors (FGF-2 and FGF-4) and insulin-like growth factor I (IGF-I) control the migration of epidermal melanoblasts in chicken wing buds. AB - The role of the apical ectodermal ridge and of fibroblast growth factors FGF-2 and FGF-4 and of the insulin-like growth factor I (IGF-I) in the control of the migration of epidermal melanoblasts was investigated using quail-chicken chimeras. Wing buds of a strain of unpigmented chicken were microsurgically modified in several ways (ablation, displacement or implantation of additional apical ectodermal ridges, implantation of grafts devoid of apical ectodermal ridges, ectopic application of growth factors) and received grafts containing quail neural crest cells. The distribution of the epidermal melanoblasts which had differentiated from the quail grafts revealed that both the apical ectodermal ridge and the growth factors invariably caused the migration of epidermal melanoblasts towards them. This leads to the conclusion that the presence of the apical ectodermal ridge is the sufficient condition to direct the migration of epidermal melanoblasts within the avian embryonic wing bud. Furthermore, FGF-2 and IGF-I and to a lesser extent FGF-4 play a decisive role in directing the migration of epidermal melanoblasts within chicken wing buds and are likely to be involved in the molecular cascade by means of which the apical ectodermal ridge controls the migration of epidermal melanoblasts. PMID- 11218061 TI - Spatial and temporal expression patterns of the cyclin-dependent kinase (CDK) inhibitors p27Kip1 and p57Kip2 during mouse development. AB - The cyclin-dependent kinase (CDK) inhibitors p27Kip1 and p57Kip2 are thought to regulate progression of the cell cycle. We have previously shown that the phenotypes of p27-/- mice are substantially different from those of p57-/- mice, suggesting that spatial and temporal expression patterns of p27Kip1 and p57Kip2 might be distinct. In this study, the roles of p27Kip1 and p57Kip2 in development were examined by characterizing their expression patterns during mouse embryogenesis by immunohistochemical analysis. Whereas certain organs and tissues (brain, lens, ganglion, lung, heart, liver, skin and kidney) expressed both proteins, others expressed only p27Kip1 (thymus, spleen, retina, testis and ovary) or only p57Kip2 (gut, palate, pancreas, cartilage and skeletal muscle). In addition, some organs expressed both p27Kip1 and p57Kip2 but showed mutually exclusive patterns of distribution among tissues. Thus, in the adrenal gland, p57Kip2 was expressed in the cortex but not in the medulla, whereas p27Kip1 was expressed in the medulla but not in the cortex. Whereas the expression of p57Kip2 in most tissues was restricted to embryogenesis, expression of p27Kip1 in many tissues was maintained in adult animals. Double-label immunofluorescence staining with either anti-p27Kip1 or anti-p57Kip2 and anti-BrdU revealed that the expression of p27Kip1 and p57Kip2 was inversely correlated with cell proliferation, suggesting that p27Kip1 and p57Kip2 are expressed exclusively in postmitotic cells. These complex spatial and temporal patterns of expression are consistent with the phenotypes of mice deficient in p27Kip1 or p57Kip2, and they suggest that these proteins might play important roles in tissue development. PMID- 11218062 TI - Mitoses of existing corticotrophs contribute to their proliferation in the rat pituitary during the late fetal period. AB - We studied the proliferation of pituitary corticotrophs quantitatively by labeling the proliferating cells with bromodeoxyuridine (BrdU) and carrying out immunocytochemistry for ACTH in rat fetuses at 19.5 days of gestation. In addition to labeling proliferating cells with a single injection of BrdU, we used double BrdU administrations at 9:00 and 19:00 for a more sensitive detection of proliferating cells. With this double administration, the number of cells labeled with either BrdU or both BrdU and ACTH increased by 1.75 and 2.3 times, respectively, compared with the single BrdU injection. The labeled cells further increased when the sections were stained for the proliferating cell nuclear antigen (PCNA) instead of BrdU. The number of cells labeled with PCNA or both PCNA and ACTH was 1.37 and 1.68 times that of the cells labeled with either BrdU or both BrdU and ACTH, respectively. The ratio of BrdU/ACTH-labeled cells or PCNA/ACTH-labeled cells to all corticotrophs was 13.6% and 24.3%, respectively, much higher than the ratios in fetuses having a single BrdU injection (6.6%). These results indicate that the mitosis of existing corticotrophs contributes greatly to their increase during the late fetal period. PMID- 11218063 TI - Differential expression of calcium-binding proteins in the red nucleus of the developing and adult human brain. AB - The adult human red nucleus consists of two parts: (1) the parvocellular part, which is clearly separated from (2) the magnocellular part. The latter and its rubrospinal projection is known to be rudimentary in the adult human brain. Information concerning the fetal or neonatal features of the red nucleus is sparse. This study is aimed at providing a detailed account of the distribution of three calcium-binding proteins: calretinin (CR), calbindin (CB), and parvalbumin (PV), which are known to be expressed in distinct neuronal populations. Special attention has been paid to transient phenomena. CB was the most abundant protein in the magnocellular part in fetal and perinatal brains; immunoreactive (ir) neurons appeared numerous and densely packed. In the adult only few and widely spaced ir nerve cells were present. CR-expression largely corresponds to that of CB, except that fewer neurons were immunolabelled. In double-labellings the majority of neurons expressed both CB and CR; a moderate number of nerve cells solely expressing CR was present in the magnocellular part. PV-ir fibers and a moderate number of small cells were observed in the fetal, perinatal as well as the adult parvocellular part. A few PV-ir neurons were seen in the magnocellular part of the fetal and perinatal brains. Our results indicated that: (1) the magnocellular and parvocellular parts of the red nucleus were well-demarcated portions from fetal life onwards, thus a dominance of the parvocellular part over the magnocellular occurred during development; (2) the magnocellular part was more prominent in the fetal period than in adulthood; (3) neurons in the red nucleus were heterogeneous with respect to the immunoreactivities towards the three calcium-binding proteins examined; (4) the transient prominence of the magnocellular part might be a substrate for a specific transitory pattern of motor behaviour. PMID- 11218064 TI - Effects of K+ channel openers on I K(ATP) of human atrial myocytes at physiological temperatures. AB - The aim of this study was to investigate the effects of the potassium channel openers (PCOs) cromakalim and pinacidil on the ATP-dependent potassium current I(K)(ATP) in human atrial myocytes. Cells were isolated from the right atrial appendage obtained during cardiac surgery. Membrane currents were studied with the patch-clamp technique in the whole-cell recording mode at 36 degrees -37 degrees C. Under physiological conditions (4.3 mmol/l ATP in the pipette solution, ATPi) I(K)(ATP) did not contribute to basal electrical activity. When ATPi was omitted from the pipette solution I(K)(ATP) activated with a time lag of 4.92+/-0.92 min (n=6) and was completely inhibited by glibenclamide. Using 4.3 mmol/l ATPi I(K)(ATP) at +30 mV was increased by 2.04+/-0.51, 7.24+/-1.65 and 13.22+/-3.71 pA/pF (n=7) with 10, 30 and 100 micromol/l cromakalim, respectively, and by 3.24+/-0.98 (n=6), 4.07+/-0.48 (n=10) and 3.46+/-1.23 pA/pF (n=6) with 10, 30 and 100 micromol/l pinacidil, respectively. Control current density was 5.39+/ 0.47 pA/pF (n=39). Using 1 mmol/l ATPi I(K)(ATP) showed a more pronounced activation (4.81+/-3.28, n=6; 9.78+/-2.60, n=7; and 15.1+/-4.18 pA/pF, n=6; with 10, 30 and 100 micromol/l pinacidil, respectively). I(K)(ATP) activated by both compounds could be effectively inhibited by glibenclamide. Repetitive exposure to pinacidil (30 micromol/l at 4.3 mmol/l ATPi) caused a potentiation of I(K)(ATP). Current density at +30 mV was increased by 87% during the first and by 401% during the second pinacidil application (n=5). The data presented in this paper provide new information about electrophysiological characteristics of human atrial I(K)(ATP) and its modulation by the PCOs cromakalim and pinacidil and suggest species-dependent differences. PMID- 11218065 TI - Lack of evidence for histamine H3 receptor function in rat ileum and human colon. AB - The effects of histamine and the more selective H3 receptor agonist (R)alpha methylhistamine were investigated on contractile responses produced by electrical stimulation of the longitudinal and circular muscles of the rat ileum and the circular muscle of the human colon. Histamine (0.1-3.0 microM) and (R)alpha methylhistamine (0.1-3.0 microM) had no significant effect (P>0.05) on cholinergic nerve stimulation of either the longitudinal or circular muscle of the rat ileum nor the circular muscle of the human colon. Substance P (1 microM) and nicotine (0.1 microM), which both produce a contraction via activation of cholinergic nerves, were also unaffected by histamine (1 microM and 10 microM) or (R)alpha-methylhistamine (1 microM and 10 microM), in either tissue. Preliminary studies using in situ hybridisation histochemistry (ISHH) were performed in rat brain and ileum in an attempt to identify H3 receptor mRNA expression. This was done using 33P-labelled oligonucleotide-specific probes for rat H3 receptor mRNA. Unlike rat brain, where H3 receptor mRNA expression was found to be abundant in several regions, no H3 receptor mRNA expression could be detected in the rat ileum under the conditions used. These findings suggest H3 receptors have no role in the modulation of cholinergic neuronal function in the rat or human intestine unlike those in the guinea-pig. Furthermore, H3 receptors appear to be absent in the rat ileum. PMID- 11218066 TI - Differences between GABA levels in Alzheimer's disease and Down syndrome with Alzheimer-like neuropathology. AB - Down syndrome (DS) is a genetic disease with developmental brain abnormalities resulting in early mental retardation and precocious, age-dependent Alzheimer type neurodegeneration. Furthermore, non-cognitive symptoms may be a cardinal feature of functional decline in adults with DS. A number of amino acids [glutamate, aspartate, gamma-aminobutyrate (GABA), glycine, taurine, glutamine, serine, arginine] were investigated in post-mortem tissue samples from temporal, occipital cortex, thalamus, caudate nucleus, and cerebellum of adult patients with Down syndrome (DS) exhibiting Alzheimer-like neuropatholgy, Alzheimer's disease (AD) and from controls by use of high performance liquid chromatography (HPLC). In DS, no significant differences from control values could be observed in any of the brain regions. In AD, significant loss of GABA content was found in the temporal cortex (0.5+/-0.2 micromol/g vs. 1.3+/-0.8 micromol/g wet weight tissue, P<0.01), occipital cortex (0.8+/-0.2 micromol/g vs. 1.4+/-0.6 micromol/g, P<0.05) and cerebellum (1.1+/-0.3 micromol/g vs. 1.8+/-0.5 micromol/g, P<0.05). Glutamate and aspartate concentrations were significantly reduced in the caudate nucleus of AD subjects (glutamate: 6.1+/-3.4 micromol/g vs. 14.7+/-1.8 micromol/g; aspartate: 1.5+/-0.3 micromol/g vs. 3.3+/-0.4 micromol/g, P<0.05). The results of this study confirm previous findings in late stage AD and provide further information with respect to DS which may be relevant to understanding different pathogenesis of cognitive and non-cognitive (behavioral) features in DS and AD. PMID- 11218067 TI - 5HT4(a) and 5-HT4(b) receptors have nearly identical pharmacology and are both expressed in human atrium and ventricle. AB - 5-Hydroxytryptamine (5-HT) increases human heart rate and atrial contractile force and hastens atrial relaxation through 5-HT4 receptors. Moreover, 5-HT may be arrhythmogenic and give rise to atrial fibrillation. It is not clear which splice variant(s) of the 5-HT4 receptor is expressed and mediates these effects of 5-HT in the human heart. Previous studies have indicated different pharmacological properties of 5-HT4 receptors in human heart and mouse colliculi neurones, possibly due to expression of different splice variants. We therefore cloned the human 5-HT4(b) receptor and compared its pharmacological properties with those of the cloned human 5-HT4(a) receptor and searched for the corresponding mRNA in human tissues. The primary structures of the two human 5 HT4 receptor splice variants are identical except for divergent C-terminal tails of 28 and 29 amino acids in the 5-HT4(a) and 5-HT4(b) receptors, respectively. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that both variants were coexpressed in various tissues, including cardiac atrium and ventricle. Additional bands suggested the presence of more than two human 5-HT4 receptor splice variants. With cloned receptors stably expressed in HEK293 cells or transiently expressed in COS-7 cells, [3H]GR 113808 consistently showed slightly higher binding affinity to h5-HT4(b) than to h5-HT4(a) receptor (pKd 0.1 0.2 log units higher). Competition of agonists, partial agonists and antagonists for [3H]GR113808 binding revealed no significant differences between the two receptors. For 5-HT4 receptor agonists and antagonists, their potencies in stimulating or inhibiting, respectively, 5-HT-stimulated adenylyl cyclase activity correlated well with their binding affinities. Tropisetron and SB207710 showed partial agonist activity at high receptor expression levels for both isoforms. Cisapride and renzapride were both partial agonists at moderate receptor levels and full agonists at high receptor levels. Cisapride was more potent than renzapride while the converse was the case in human atrium, for which cisapride had lower affinity and agonist potency than at the recombinant receptors. The binding affinities and agonist potencies of ligands for both 5 HT4(a) and 5-HT4(b) receptors correlated with the corresponding affinities and potencies in human atrium. The agonist potency of SB207710 was around 10 times lower than its binding and blocking affinity for both splice variants, suggesting that activation of adenylyl cyclase and blockade of 5-HT responses are mediated through different conformational states. The similar pharmacological properties of the two human 5-HT4 receptor splice variants together with their expression in human atrium would be consistent with mediation of the cardiostimulant effects of 5-HT through both variants. However, the effects of cisapride appear either mediated through non-a and non-b splice variants of the 5-HT4 receptor or 5 HT4(a) and 5-HT4(b) receptor expression in human atrial cells alters somewhat their pharmacological profile through still unknown mechanisms. PMID- 11218068 TI - Characterization of the locomotor activity-inhibiting effect of nociceptin/orphanin FQ in mice. AB - Nociceptin/orphanin FQ (NC) modulates spontaneous locomotor activity (LA) in mice. NC applied intracerebroventricularly (i.c.v.) has been reported to stimulate LA at low doses (0.001-0.01 nmol) while inhibiting LA at higher doses (1-10 nmol). In the present study, the effects of NC on LA in mice were evaluated and the receptor involved characterized using NC receptor (OP4) agonists and antagonists. No significant differences were found in the LA (30-min observation period) between non-injected mice, mice injected with saline (2 microl/mouse, i.c.v.), or with low doses of NC (0.001 nmol and 0.01 nmol). In the 0.1-10 nmol range, NC caused a dose-dependent, naloxone-insensitive reduction of LA. The effects of the natural peptide were mimicked by NCNH2 and NC(1-13)NH2 while shorter fragments were inactive (NC(1-12)NH2, NC(1-9)NH2). [Phe1psi(CH2 NH)Gly2]NC(1-13)NH2 ([F/G]NC(1-13)NH2) was inactive at 0.1 nmol and 1 nmol, while causing a partial reduction of LA at 10 nmol. One nmol of the pseudopeptide also prevented the inhibitory effect of 1 nmol NC. Ten nmol [Nphe1]NC(1-13)NH2 did not modify LA per se, but fully prevented the inhibitory action of 1 nmol NC. Results indicate that [F/G]NC(1-13)NH2 and [Nphe1]NC(1-13)NH2 behave as a partial agonist and a pure antagonist of OP4 sites, respectively. Taken together, these data demonstrate that NC inhibits LA in mice by activating OP4 receptor sites. PMID- 11218069 TI - Differential effects of dofetilide, amiodarone, and class lc drugs on left and right atrial refractoriness and left atrial vulnerability in pigs. AB - OBJECTIVES: Antiarrhythmic drugs have been shown to prolong right atrial refractoriness while data on the left atrium are not available. In pigs we have observed shorter effective refractory periods (ERP) of the left compared with the right atrium associated with a much higher left atrial vulnerability for tachyarrhythmias. Since this could suggest a different distribution of repolarizing ion channels in left and right atrium, we investigated whether antiarrhythmic drugs blocking different ion channels have a differential effect on left and right atrial ERP and left atrial vulnerability. METHODS: In pentobarbital-anesthetized pigs (n=40) we measured and compared ERPs in both atria before and after different drugs with the S1-S2 extrastimulus method at three basic cycle lengths (BCL) and assessed the inducibility of atrial fibrillation/flutter (AF/AFL) by the premature S2 stimulus. RESULTS: At the three BCL tested (240/300/400 ms) baseline ERPs were shorter in left vs. right atrium (112+/-2/124+/-2/129+/-2 ms vs. 147+/-2/163+/-2/167+/-2 ms, P<0.001). Mostly non sustained AF/AFL induced by the S2 extrastimulus was very frequent in the left (68%) and nearly absent in the right atrium (3%). Only amiodarone, 5 mg/kg i.v., which showed a balanced increase of left and right atrial ERP (29+/-5/33+/-4/35+/ 3% vs. 30+/-5/35+/-5/42+/-7%), decreased the inducibility of AF/AFL significantly (-72%, P<0.01). Dofetilide, 10 microg/kg i.v., had a stronger effect on right than left atrial ERP (36+/-4/39+/-5/46+/-10% vs. 23+/-2/22+/-7/22+/-5%, P<0.05), while flecainide, 1 mg/kg i.v., prolonged left more than right atrial ERP (58+/ 15/36+/-7/40+/-7% vs. 26+/-5/24+/-5/21+/-4%, P<0.05) similar to 1 mg/ kg of propafenone (46+/-5/45+/-7/32+/-10% vs. 17+/-4/21+/-5/ 25+/-8%, P<0.05). CONCLUSION: The shorter refractoriness of the left compared with the right atrium observed in pigs was associated with a high left atrial vulnerability for tachyarrhythmias, which was reduced only by amiodarone showing a balanced increase of left and right atrial ERP. Dofetilide was stronger on right atrial ERP, flecainide and propafenone on left atrial ERP. These differences suggest a differential distribution of repolarizing ion channels between left and right atrium with possible relevance for the antiarrhythmic efficacy of drugs. PMID- 11218070 TI - Differences in electromechanical coupling between bradykinin and the nonpeptide kinin B2 receptor agonist, FR 190997, in the circular muscle of guinea-pig colon. AB - We have compared the effect of bradykinin (BK) and the nonpeptide kinin B2 receptor agonist, FR 190997, in producing changes in membrane potential and tension in the circular muscle of guinea-pig colon by the sucrose gap technique. In the presence of atropine (1 microM), S-ketoprofen (3 microM) and apamin (0.1 microM), BK (1 microM for 20 s) induced a transient depolarization of the membrane with superimposed action potentials (spikes) and transient contraction. Nifedipine (1 microM) eliminated the spikes and markedly inhibited the BK-induced contractions. FR 190997 (3-10 microM for 20 s) induced a slowly developing sustained small depolarization associated with a slowly developing and sustained contraction but, contrary to BK, FR 190997 was unable to trigger spikes. Nifedipine had no effect on depolarization and contraction induced by FR 190997. In the presence of 1 microM nifedipine, the combined application of a blocker of receptor-operated cation channels, SKF 96365 (50 microM for 30 min), and of an inhibitor of sarcoplasmic reticulum calcium pump, cyclopiazonic acid (CPA 10 microM for 30 min), reduced the BK-induced depolarization and contraction by about 45%-60%. The same treatment induced about 40% reduction of the sustained contraction induced by FR 190997, whereas the concomitant depolarization was not significantly affected. The tyrosine kinase inhibitor genistein (40 microM for 20 min) had no effect on the BK- and FR 190997-induced depolarization and contraction in the presence of nifedipine. In radioligand binding experiments performed in membranes of colonic smooth muscle cells, both agonists displaced the [3H]BK specific binding with a pIC50 of 9.6 and 8.5 for BK and FR 190997, respectively. These findings indicate a substantial qualitative difference in mechanisms of excitation contraction coupling activated by BK and FR 190997 via B2 receptors in guinea-pig colon. PMID- 11218071 TI - Anticonvulsant and sodium channel blocking activity of higher doses of clenbuterol. AB - Clenbuterol, a lipophilic beta2-adrenoceptor agonist, was investigated in various seizure models of experimental epilepsy. In the maximal electroshock seizure threshold test, clenbuterol (> or =4 mg/kg i.p.) increased the electroconvulsive threshold for tonic seizures in mice. In the traditional maximal electroshock seizure (MES) test in mice, ED50 values of 11 mg/kg i.p. or s.c. were determined. In both models, the beta2-receptor antagonist ICI 118.551 did not antagonize the anticonvulsant activity of clenbuterol. Combinations of clenbuterol with standard antiepileptics revealed additive anticonvulsant effects. Repeated administration of clenbuterol (5 mg/kg s.c., twice daily for 14 days) to mice did not significantly influence its anticonvulsant potency or the effectiveness of phenobarbital in the MES test. In various chemically-induced seizure tests with tonic convulsions, clenbuterol inhibited or tended to suppress the tonic phase. However, this drug was not effective in preventing clonic seizures in the pentylenetetrazol (85 mg/kg s.c.) seizure threshold test. In the rotarod ataxia test (mice), a minimal "neurotoxic" dose (TD50) of 41 mg/kg i.p. was determined. In unrestrained rats with chronically implanted electrodes in the dorsal hippocampus, clenbuterol (2 mg/kg and 4 mg/kg i.p.) significantly reduced the duration of electrically evoked hippocampal afterdischarges. In amygdala-kindled rats, clenbuterol (5 mg/kg and 10 mg/kg i.p.) reduced the seizure severity to stage 3. Additional studies indicated that clenbuterol (6 mg/kg i.p.) increased the heart rate and decreased the blood pressure, but this drug did not alter the plasma level of the two tested antiepileptics phenobarbital and carbamazepine. Furthermore, in whole-cell voltage-clamp experiments on cultured neonatal rat cardiomyocytes, clenbuterol (1-100 microM) depressed the fast sodium current in a concentration- and frequency-dependent manner. In conclusion, the anticonvulsant effects of higher doses of clenbuterol against generalized tonic-clonic and complex partial seizures seem to be related to the inhibition of voltage dependent sodium channels and not to the modulation of beta-adrenoceptors. PMID- 11218072 TI - Sanguinarine induces K+ outflow from yeast cells expressing mammalian sodium pumps. AB - Sanguinarine, an alkaloid from Sanguinaria canadensis, has no effect on the yeast Saccharomyces cerevisiae at concentrations of up to 225 microM. Yeast cells become sensitive to sanguinarine and lose cytosolic K+ in a time- and concentration-dependent manner when they express the mammalian Na+,K+-ATPase (sodium pump). Dose-response studies show that sanguinarine induces K+ outflow from cells expressing wild-type sodium pumps with an EC50 of 29.3+/-1.2 microM. A similar effect with a comparable EC50) of 26.8+/-1.3 microM is obtained with cells expressing an Asp369Ala mutant of the sodium pump alpha1 subunit. Since this sodium pump mutant does not hydrolyze ATP, it can be excluded that the observed sanguinarine-induced outflow of K+ is an active ion transport process. Ouabain inhibits the sanguinarine effect at concentrations higher than 1 mM. In contrast, proscillaridin A inhibits the sanguinarine-induced K+ outflow from cells expressing the wild-type sodium pump with an IC50 of 48.9+/-1.3 microM. A similar IC50 of 52.2+/-3.0 microM is obtained with cells expressing the Asp369Ala mutant. These data, together with the fact that sanguinarine inhibits the binding of [3H]ouabain to microsomes prepared from yeast cells expressing the sodium pump with an IC50 of 94.5+/-4.3 microM, all indicate that sanguinarine specifically targets the sodium pump, and that the observed K+ outflow is tightly associated with the presence of the enzyme. PMID- 11218073 TI - Effects of repeated cocaine treatment on striatal dopamine release in alcohol preferring AA and alcohol-avoiding ANA rats. AB - Modulation of striatal dopamine (DA) release by acute or repeated cocaine treatment was studied in the nucleus accumbens and caudate-putamen of alcohol preferring (AA, Alko Alcohol) and alcohol-avoiding (ANA, Alko Non-Alcohol) rats. Cocaine (5-10 mg/kg i.p.) was administered daily for 4 days and the concentrations of extracellular DA measured by in vivo microdialysis on days 1 and 4 in the freely moving rats. The first administration of cocaine increased DA concentration similarly in rats of both lines in both the nucleus accumbens and caudate-putamen. On the 4th day, the effect of cocaine was significantly larger in the nucleus accumbens of AA than in that of ANA rats, whereas no such enhanced effect of cocaine was found in the caudate-putamen of either line. The results suggest that mesolimbic DA release in response to cocaine is sensitized more readily in AA than in ANA rats, which would not only render the former more susceptible to alcohol, but to other drugs of abuse, and might explain our previous findings that AA rats are more susceptible to psychomotor sensitization than ANA rats. PMID- 11218074 TI - Troglitazone and rosiglitazone induce apoptosis of vascular smooth muscle cells through an extracellular signal-regulated kinase-independent pathway. AB - Recent evidence suggests that apoptosis may be involved in the control of vascular smooth muscle cell (VSMC) number in atherosclerotic lesions. The peroxisome proliferator-activated receptor gamma (PPARgamma) ligands thiazolidinediones have been reported to induce apoptosis in macrophages and in a variety of tumor cell lines. To evaluate whether these agents also induce apoptosis in VSMC, cultured rat VSMC were treated with increasing doses of the thiazolidinedione analogues troglitazone (TRO) and rosiglitazone (RSG). Both ligands induced cell death in a concentration-dependent manner (EC50 12.1+/-3.3 microM and 1.43+/-0.39 microM, respectively), causing almost complete cell death at the highest concentrations (100 microM and 10 microM for TRO and RSG, respectively), along with an expected parallel decrease in [3H]thymidine uptake into cell DNA (EC50 6.7+/-2.4 microM and 0.75+/-0.19 microM, respectively). The cell count was determined by the coulter counter principle. Furthermore two apoptotic markers were measured, the caspase 3 activity and the cytoplasmic histone-associated DNA fragments, both of which were significantly increased when the aforementioned high concentrations were used. This indicates that apoptosis is involved in the TRO- and RSG-induced VSMC growth suppression. The same concentrations of TRO and RSG caused an unexpected stimulation of the extracellular signal-regulated response kinases 1 and 2 (ERK1/2) and stimulated the p38 mitogenic-activated protein (MAP) kinase as determined by Western blotting. In order to establish whether the proapoptotic effects of TRO and RSG are mediated through ERK1/2 activation, we used the selective MAP kinase kinase (MEK) inhibitor PD98059 (20 microM), which suppressed the TRO- and RSG-induced ERK1/2 activation but did not abolish their proapoptotic effects. We conclude that the thiazolidinedione analogues TRO and RSG induce cell death due to apoptosis in VSMC through an ERK1/2-independent pathway. PMID- 11218075 TI - Pharmacological characterisation of the decrease in 5-HT synthesis in the mouse brain evoked by the selective serotonin re-uptake inhibitor citalopram. AB - The selective serotonin re-uptake inhibitor (SSRI) citalopram decreases the synthesis of 5-hydroxytryptamine (5-HT) in the mouse brain in vivo. The underlying mechanism was studied by recording the accumulation of 5 hydroxytryptophan (5-HTP) in hypothalamus and hippocampus after inhibition of the aromatic amino acid decarboxylase activity with m-hydroxybenzylhydrazine (NSD 1015). Depletion of 5-HT with reserpine markedly reduced the citalopram-induced decrease of 5-HTP but not that evoked by the 5-HT1A receptor agonist 8-OH-DPAT, which indicates that the presence of endogenous 5-HT is necessary for full effect of citalopram. In contrast to the almost complete antagonism of the decrease in 5 HT synthesis induced by 8-OH-DPAT, the 5-HT1A receptor antagonist WAY-100,635 only slightly affected the citalopram-evoked decrease in 5-HT synthesis. Likewise, the 5-HT1B receptor antagonists NAS-181 and GR127935 only slightly antagonised the citalopram effect although they strongly inhibited the decrease in 5-HT synthesis induced by the 5-HT1B receptor agonist anpirtoline. Combined treatment with 5-HT1A and 5-HT1B receptor antagonists did not produce any additive antagonistic effect on the citalopram-induced decrease in 5-HT synthesis. The 5-HT2A/2C receptor antagonist ketanserin, the 5-HT3 receptor antagonist ondansetron and the 5-HT4 receptor antagonist RS-39604 had no effect on the citalopram-induced decrease in 5-HT synthesis. The same was found for several other non-selective 5-HT receptor antagonists, e.g. cyproheptadine, dihydroergotamine, methiothepin, methysergide, metergoline and mianserin. It is concluded that the citalopram-induced decrease in 5-HT synthesis differs in sensitivity from that mediated by 5-HT1A or 5-HT1B receptor agonists and citalopram also seems to require endogenous 5-HT for its full effect. PMID- 11218076 TI - Aspirin, but not the more selective cyclooxygenase (COX)-2 inhibitors meloxicam and SC 58125, aggravates postischaemic cardiac dysfunction, independent of COX function. AB - Inhibition of cyclooxygenase (COX) might favour non-enzymatic formation of cardiodepressive isoprostanes from arachidonic acid by radicals generated during reperfusion. This could explain deleterious effects of acetylsalicylic acid (ASA) on cardiac function. We examined the influence of COX inhibition on myocardial function after low-flow ischaemia and reperfusion, employing either ASA (100 micromol/l), the partially selective COX-2 inhibitor meloxicam (0.3 micromol/l and 3.0 micromol/l), or the highly selective COX-2 inhibitor SC 58125 (1.0 micromol/l and 3.0 microgmol/l). Isolated, buffer-perfused guinea pig hearts, performing pressure-volume work before and after consecutive low-flow ischaemia and reperfusion, were used for the study. Measurement of coronary and aortic flow, ejection time and heart rate served to calculate external heart work (EHW), before and after ischaemia. Additionally, release of prostacyclin and thromboxane A2, production of lactate, consumption of pyruvate and tissue concentration of the isoprostane 8-iso-PGF2alpha were measured. ASA significantly reduced recovery of EHW (46+/-18% vs. 82+/-15% for controls), whereas meloxicam and SC 58125 did not (64+/-15% and 74+/-13% recovery, respectively). Paradoxically, ASA increased reactive hyperaemia and consumption of pyruvate in the early reperfusion phase in comparison to all other groups, while lactate production did not differ. Prostacyclin production did not increase during reperfusion and was not significantly different between groups at any time point. In contrast, thromboxane A2 release increased about fivefold in the 2nd min of reperfusion under control conditions and in the presence of SC 58125, but was inhibited by ASA and by meloxicam in both concentrations. Isoprostane content of heart tissue was not detectably influenced under the mild reperfusion conditions used here. We conclude that ASA can aggravate postischaemic cardiac dysfunction, independent of COX inhibition. The deleterious effect in the present model might be due to uncoupling of mitochondrial oxidative phosphorylation rather than to direct effects of reduced eicosanoid release or radical induced formation of isoprostanes. PMID- 11218077 TI - Cannabinoid CB1-mediated inhibition of stress-induced gastric ulcers in rats. AB - The effect of cannabinoid drugs (i.p.) on cold/restraint stress-induced gastric ulcers was studied in rats. The cannabinoid receptor agonist (WIN 55,212-2, 0.1-1 mg/kg), but not the less active isomer WIN 55,212-3 (1 mg/kg), reduced gastric ulceration. The protective effect of WIN 55,212-2 (1 mg/kg) was counteracted by the cannabinoid CB1 receptor antagonist SR141716A, but not by the cannabinoid CB2 receptor antagonist SR144528. These results indicate that the antiulcer effect of the cannabinoid receptor agonist WIN 55,212-2 is mediated by cannabinoid CB1 receptors. PMID- 11218078 TI - Linkage mapping in populations with karyotypic rearrangements. AB - A simulation study was used to examine the consequences of karyotypic rearrangements on molecular genetic map construction. Two groups of 50 datasets were created for F2 populations segregating for a reciprocal translocation of chromosomal segments or a reciprocal translocation and inversion. Multiple attempts were made to construct maps for each dataset using MapMaker/EXP. As expected, the markers from segments involved in the translocation formed one linkage group. Maps that corresponded to the known marker order within a segment could be constructed by the following method. The separation of markers distal to the translocation breakpoints into their respective segments could be made by constructing multiple maps, using distinct orders of marker entry, and observing the variances in intermarker distances: variances between pairs of markers from the same segment were an order of magnitude less compared to pairs where markers were from different segments. The order of markers within a segment could be determined from combining the pairwise linkage results from multiple maps, or from maps including all markers from a segment. No bias in map distances was observed. These results indicate that, under conditions similar to those tested, genetic maps corresponding to the segments conserved in translocations can be constructed. PMID- 11218079 TI - Integration of simple sequence repeat (SSR) markers into a molecular linkage map of common bean (Phaseolus vulgaris L.). AB - Microsatellite or simple sequence repeat (SSR) markers have been successfully used for genomic mapping, DNA fingerprinting, and marker-assisted selection in many plant species. Here we report the first successful assignment of 15 SSR markers to the Phaseolus vulgaris molecular linkage map. A total of 37 SSR primer pairs were developed and tested for amplification and product-length polymorphism with BAT93 and Jalo EEP558, the parental lines of an F7 recombinant inbred (RI) population previously used for the construction of a common bean molecular linkage map. Sixteen of the SSRs polymorphic to the parental lines were analyzed for segregation and 15 of them were assigned to seven different linkage groups, indicating a widespread distribution throughout the bean genome. Map positions for genes coding for DNAJ-like protein, pathogenesis-related protein 3, plastid located glutamine synthetase, endochitinase, sn-glycerol-3 phosphate acyltransferase, NADP-dependent malic enzyme, and protein kinase were determined for the first time. Addition of three SSR loci to linkage group B4 brought two separated smaller linkage groups together to form a larger linkage group. Analysis of allele segregation in the F7 RI population revealed that all 16 SSRs segregated in the expected 1:1 ratio. These SSR markers were stable and easy to assay by polymerase chain reaction (PCR). They should be useful markers for genetic mapping, genotype identification, and marker-assisted selection of common beans. PMID- 11218080 TI - Erwin Baur or Carl Correns: who really created the theory of plastid inheritance? AB - Historical reviews of the field of non-Mendelian genetics and many other publications credit Erwin Baur and Carl Correns equally for the development of the theory of plastid inheritance. However, a study of the original literature indicates that this conclusion is not correct. Analysis of the relevant articles leads to the conclusion that Baur alone deserves credit for the theory of plastid inheritance. In his classic article on the inheritance properties of white margined Pelargonium plants, Baur (1909) stated: (1) The plastids are carriers of hereditary factors which are able to mutate. (2) In variegated plants, random sorting-out of plastids is taking place. (3) The genetic results indicate a biparental inheritance of plastids by egg cells and sperm cells in Pelargonium. By contrast, Correns held the view that in variegated plants there is a maternally transmitted labile state of the cytoplasm which switches either to a permanently "healthy" state (allowing the "indifferent" plastids to become green chloroplasts) or to a permanently "diseased, ill" cytoplasmic state (causing white plastids and cells). Otto Renner supported Baur's theory and worked out important characteristics of plastid inheritance in the genus Oenothera. In the 1930s Renner reported many more observations, which established plastid inheritance as a widely accepted genetic theory. PMID- 11218081 TI - Physical location of homoeologous groups 5 and 6 molecular markers mapped in Triticum aestivum L. AB - In situ hybridization was used to map 21 restriction fragment length polymorphism (RFLP) probes to linkage groups 5 and 6 of hexaploid wheat (Triticum aestivum L. em Thell.) in order to compare physical distances and genetic distances between adjacent markers. All 21 probes hybridized to the corresponding homoeologous chromosome arms. The linear order and linkage relationships among the DNA probes on the in situ-based physical maps were generally the same as those on the RFLP based genetic maps. However, significant differences were observed between the centiMorgan distances on a linkage map and the physical distances of the probes using in situ-based techniques. The results indicated a clustering of polymorphic RFLP markers in the middle of all of the homoeologous group 5 and 6 chromosome arms. This suggests that the available linkage maps do not completely cover the physical length of the chromosomes. As with the genetic maps, the physical map clearly showed the presence of nonhomoeologous rearrangements in the terminal regions of chromosome arms 5AL and 6BS. However, the physical mapping gave an indication of the physical size of the rearrangements as well as their arm location. PMID- 11218083 TI - A comparison of RAPD versus microsatellite DNA markers in population studies of the massasauga rattlesnake. AB - We compared genetic differentiation among populations of the threatened massasauga rattlesnake (Sistrurus c. catenatus) using two types of nuclear molecular markers: randomly amplified polymorphic DNA (RAPD) markers and microsatellites. Analyses of molecular variance (AMOVA) and G(ST) and F(ST) analyses indicated that levels of among-population differentiation between regional populations (>100 km) were comparable for both markers. However, microsatellites were superior in population assignment tests and at discerning fine-scale genetic differentiation between subpopulations separated by tens of kilometers. These results argue that both types of markers are suitable for defining broad-scale genetic structures in snake populations and can provide important inputs into conservation initiatives of focal taxa. However, our analyses suggest that microsatellites 3re better for detecting structure at limited spatial scales. PMID- 11218082 TI - Genetic diversity and population structure of 20 North European cattle breeds. AB - Blood samples were collected from 743 animals from 15 indigenous, 2 old imported, and 3 commercial North European cattle breeds. The samples were analyzed for 11 erythrocyte antigen systems, 8 proteins, and 10 microsatellites, and used to assess inter- and intrabreed genetic variation and genetic population structures. The microsatellites BoLA-DRBP1 and CSSM66 were nonneutral markers according to the Ewens-Watterson test, suggesting some kind of selection imposed on these loci. North European cattle breeds displayed generally similar levels of multilocus heterozygosity and allelic diversity. However, allelic diversity has been reduced in several breeds, which was explained by limited effective population sizes over the course of man-directed breed development and demographic bottlenecks of indigenous breeds. A tree showing genetic relationships between breeds was constructed from a matrix of random drift-based genetic distance estimates. The breeds were classified on the basis of the tree topology into four major breed groups, defined as Northern indigenous breeds, Southern breeds, Ayrshire and Friesian breeds, and Jersey. Grouping of Nordic breeds was supported by documented breed history and geographical divisions of native breeding regions of indigenous cattle. Divergence estimates between Icelandic cattle and indigenous breeds suggested a separation time of more than 1,000 years between Icelandic cattle and Norwegian native breeds, a finding consistent with historical evidence. PMID- 11218084 TI - Masculinization mechanism of hybrids in bitterlings (Teleostei: Cyprinidae). AB - The sex ratio of bitterling hybrids (subfamily: Acheilognathinae) is often likely to be biased toward males. Artificial hybridization was carried out in 10 species of bitterlings (three genera) in order to elucidate the masculinization mechanism of hybrids. Tanakia himantegus never produced viable F1 hybrids with other species, while hybrids of most other species were viable. In terms of sex ratio and fertility, hybrids were clearly divided into two groups: congeneric Tanakia hybrids and others. Both male and female congeneric Tanakia hybrids were fertile. The sex ratio was nearly 1:1 in all groups of Tanakia hybrids. Except for the congeneric Tanakia hybrids, sterile males appeared predominantly in groups of hybrids in which females were very rare but remained fertile. Sterile intersexes were also observed in five hybrid groups: T. lanceolata (female) x Acheilognathus cyanostigma (male), Rhodeus uyekii (female) x T. lanceolata (male), A. rhombeus (female) x T. lanceolata (male), A. rhombeus (female) x T. limbata (male), and A. tabira tabira (female) x A. cyanostigma (male). In the development of male predominant hybrids, although hybrid and control (parental species) hatching and survival rates do not differ, no females appeared in hybrids, contrary to the controls. Taking the female heterogametic sex-determining system (ZW) and the phylogenetic relationship of bitterlings into consideration, the masculinization mechanism of hybrids in bitterlings can be explained by the interaction of two sex chromosomes, derived from each parental species. The basic genetic sex in bitterlings is male (ZZ) and the derivative is female (ZW). When parental species are related, the sex phenotype of hybrids coincides with the genetic sex. However, when the parental species differ, the sex phenotype of the ZW genotype is reversed to become male by an abnormal interaction between the Z and W chromosomes. The rare appearance of females and intersexes in male-predominant hybrids might be due to complete or partial functional expression of the W chromosome. PMID- 11218085 TI - Genetic dissection of honeybee (Apis mellifera L.) foraging behavior. AB - We demonstrate the effects of a new quantitative trait locus (QTL), designated pln3, that was mapped in a backcross population derived from strains of bees selected for the amount of pollen they store in combs. We independently confirmed pln3 by demonstrating its effects on individual foraging behavior, as we did previously for QTLs pln1 and pln2 (Hunt et al. 1995). QTL pln2 is very robust in its effects on foraging behavior. In this study, pln2 was again shown to affect individual foraging behavior of workers derived from a hybrid backcross of the selected strains. In addition, pln2 was shown to affect the amount of pollen stored in combs of colonies derived from a wide cross of European and Africanized honeybees. This is noteworthy because it demonstrates that we can map QTLs for behavior in interstrain crosses derived from selective breeding and study their effects in unselected, natural populations. The results we present also demonstrate the repeatability of finding QTLs with measurable effects, even after outcrossing selected strains, suggesting that there is a relatively small subset of QTLs with major effects segregating in the population from which we selected our founding breeding populations. The different QTLs, pln1, pln2, and pln3, appear to have different effects, revealing the complex genetic architecture of honeybee foraging behavior. PMID- 11218086 TI - Inheritance of resistance in smooth bromegrass to the crown rust fungus. AB - Common smooth bromegrass (Bromus inermis Leyss.) is octoploid, 2n = 8x = 56, with a genome structure of AAAAB1B1B2B2. Tetrasomic inheritance patterns have been observed in smooth bromegrass, but disomic inheritance is also expected from cytologic observations. Smooth bromegrass is susceptible to the crown rust fungus (Puccinia coronata Corda.). The objective of this study was to determine the inheritance of smooth bromegrass resistance to P. coronata. Seven smooth bromegrass clones, three susceptible and four resistant, were selfed and crossed in a diallel with bulked reciprocals. Inoculations were made with a population of P. coronata from PL-BDR1 smooth bromegrass. Resistance of smooth bromegrass to this population of P. coronata is complex. At least three genes appear to be involved in this host-pathogen interaction, one tetrasomic dominant gene which determines susceptibility (S) and two dominant genes (R1 and R2) that may be complementary and could be inherited either tetrasomically or disomically. Other genes may be involved in the smooth bromegrass-P. coronata interaction, possibly accounting for the lack of fit to expected ratios of some progeny. Heterogeneity for avirulence phenotype in the pathogen population may also have contributed to lack of fit of some progeny. Multiple resistance genes were detected because a pathogen population, likely consisting of genotypes with different genes for virulence, was used to challenge the host. PMID- 11218087 TI - Isolation, mapping, and characterization of two barley multiovary mutants. AB - Mutations in homeotic genes disturb the spatial and temporal patterns of development, often leading to the appearance of tissues in abnormal locations. Many homeotic genes, involved in flower development, code for proteins with a highly conserved domain called the MADS box, which acts as a sequence-specific DNA binding protein. Two floral development mutants were isolated from a fast neutron irradiated M2 barley population. The phenotypes are multiovary, that is, stamens replaced with carpels, designated mo7a, and stamens replaced with carpels and lodicules converted to leaflike structures, designated mo6b. These phenotypes resemble the Arabidopsis mutants APETALA3 (AP3) and PISTILATA (PI). The mo6b and mo7a mutants were mapped to the centromeric region of chromosome 1 (7H) and to the telomeric region of chromosome 3 (3H), respectively. PMID- 11218088 TI - The Evergreen gene is essential for flower initiation in carnation. AB - One of the leading cut-flower crops in the world, the greenhouse carnation (Dianthus caryophyllus), has been subjected to intense breeding efforts for the past few hundred years. As an ornamental crop, flowering and flower architecture are major breeding targets that are constantly in demand. In an ongoing breeding program aimed at improving these characteristics, two mutants heterozygous for a mutation in a gene termed evergreen (e) were identified. In these mutants, spike like clusters of bracteoles subtend each flower. Genetic analysis of the mutants confirmed the semidominant nature of this nuclear mutation and that the two original mutants were allelic at the evergreen locus. In homozygous mutant plants, a more severe phenotype was observed. Flower formation was completely blocked and spikelike clusters of bracteoles did not subtend any flowers. Morphological characterization of mutant plants revealed that vegetative growth and inflorescence structure are not affected by the mutant allele. In plants heterozygous for the evergreen mutation, fertility, petal and pistil length, calyx diameter, and stamen number were not affected. However, flowers from these heterozygous plants had a reduced number of petals, suggesting an intriguing link between evergreen and the double flower (d) gene that determines petal number in carnation. The control by evergreen of bracteole formation, floral meristem initiation, and petal number in carnation is discussed in comparison to the recessive leafy (lfy) and floricaula (flo) mutants of Arabidopsis and Antirrhinum, respectively. PMID- 11218089 TI - Floral-color polymorphism in Ipomoea purpurea: biased inheritance of the dark allele is not a general explanation for its maintenance. AB - A previous investigation reported the existence in a single population of the morning glory (Ipomoea purpurea) of non-Mendelian inheritance at the W locus influencing flower color. In addition, it was shown that the magnitude of biased inheritance in that population was sufficient to maintain a floral-color polymorphism at that locus at frequencies approximating those observed in natural populations. The current investigation was undertaken to determine whether this biased inheritance was characteristic of other I. purpurea populations, and thus whether it provides a general explanation for maintenance of the polymorphism. The current study found no evidence for biased inheritance in two additional polymorphic populations examined. Non-Mendelian inheritance thus seems unlikely to constitute a general explanation for the maintenance of this floral-color polymorphism in l. purpurea. PMID- 11218090 TI - Genetic variability in the Iberian imperial eagle (Aquila adalberti) demonstrated by RAPD analysis. AB - RAPD analysis was used to estimate the genetic diversity in an Iberian imperial eagle (Aquila adalberti) population, one of the most threatened bird species in the world. Forty-five of 60 arbitrarily designed primers amplified 614 loci in 25 individual eagles, 59.7% of which were polymorphic. In contrast to the traditional allozyme analysis performed in a previous study, the RAPD method has revealed a high level of heterozygosity in this species (H = 0.267+/-0.008). The genetic distances estimated between 25 eagles can serve to establish more adequate mating in order to preserve genetic variability. Conservation efforts being carried out in Spain in this species might be successful based on the results obtained in the present work. PMID- 11218091 TI - Genetic analyses of plumage color mutations on the Z chromosome of Japanese quail. AB - Genetic analyses were performed with four sex-linked plumage color mutations (roux, brown, imperfect albino, and cinnamon) in Japanese quail (Coturnix japonica). Roux and brown quail have similar plumage color, but plumage of roux quail is paler. Pure, F1 and F2 matings were carried out with roux and brown stocks, and 357, 338, and 273 progeny with either roux or brown plumage color were obtained from each mating type, respectively. These allelism tests showed that mutations for roux and brown colors were alleles (*R and *B) from the same locus BR, and that BR*B was dominant over BR*R. Two alleles at the AL locus, AL*A (imperfect albino) and AL*C (cinnamon) were used to estimate the recombination frequency between the BR and AL loci on the Z chromosome. It was estimated to be 38.1+/-1.0% based on 4615 chicks from the test crosses. PMID- 11218092 TI - Fifty microsatellite markers for Japanese quail. AB - A Japanese quail genomic library enriched for (CA/GT)n simple sequence repeats was screened and positive clones were sequenced. Fifty original microsatellite sequences were isolated that consisted mainly of perfect repeats of the dinucleotide (CA/GT)n motif and a corresponding number of polymerase chain reaction (PCR) primer pairs complementary to unique DNA sequences flanking the microsatellite repeats were designed to detect the repeats. Forty-six percent (23 of 50) of the markers revealed polymorphism in two unrelated quail individuals (one male and one female) randomly sampled from a population of wild quail origin. All 50 primer pairs were tested in the PCR for their ability to amplify chicken genomic DNA. Amplification products were obtained for 14 (28.0%) of the markers at the annealing temperature optimized for quail. These results provide an opportunity to begin characterizing the quail genome for the development of a genetic map for this economically valuable species and the eventual construction of a comparative genetic map in Phasianidae, which comprises a number of agriculturally important species of poultry. PMID- 11218093 TI - SIMCOAL: a general coalescent program for the simulation of molecular data in interconnected populations with arbitrary demography. PMID- 11218094 TI - SPAM (version 3.2): statistics program for analyzing mixtures. PMID- 11218095 TI - Linear and nonlinear analysis of the stability of gestural organization in speech movement sequences. AB - Recent procedures have been developed that allow the analysis of gestural stability across repetitions of phrase-length utterances by linearly normalizing aspects of the articulatory signal. This process produces an index of variability called spatiotemporal index, or STI (Smith, Goffman, Zelaznik, Ying, & McGillem, 1995). Consistent findings that different STIs underlie changes in speaking rates in normally speaking adults have been found in subsequent studies by Smith and colleagues. However some researchers have raised concerns that linearly normalized data do not adequately account for the nonlinear aspects in the articulatory signal (Lucero, Munhall, Gracco, & Ramsey, 1997). The present study compared findings from linear and nonlinear normalization procedures in the analysis of lower-lip displacement of phrase-length utterances for a group of 8 speakers and across three rates. Findings indicated that at a group level, gestural stability, although higher for each rate contingency, was similar to that found in earlier STI studies. However, variability was greater, and 4 of the 8 subjects failed to consistently demonstrate greater stability at habitual rate, followed by fast and then slow rate. A nonlinearly normalized analysis of the same data produced significantly lower stability indices, and variability was also reduced. It is argued that a nonlinear normalization procedure based on lower-lip displacement holds advantages in the analysis of phrase-length speech data over both linear and alternative nonlinear normalization techniques. PMID- 11218096 TI - Acoustic comparison of vowel articulation in normal and reverse phonation. AB - Acoustic characteristics of the vowels /i,u,a/ produced by adult females and males during normal phonation were compared with the same vowels produced on deliberate ingressive airflow (i.e., "reverse" phonation). Results of the analysis revealed the average fundamental frequency (F0) of reverse phonation to be significantly higher than the corresponding normal phonations. There were no significant differences noted in the vocal tract resonance (F1 and F2 frequency) values for /i/ during normal and reverse phonation. However, the F1 values for /a/ were significantly lower, and the F2 values for /u/ significantly higher, during reverse phonation. The results are discussed with regard to differences in the articulatory control of the speech mechanism during reverse phonation as compared to normal expiratory phonation. Also discussed are the implications of using reverse phonation as a voice management technique. PMID- 11218097 TI - Respiratory markers of conversational interaction. AB - Respiratory movements were recorded from 10 dyads (20 subjects) during quiet breathing, reading aloud, spontaneous monologue, scripted dialog, and spontaneous conversation. Timing measures of inspiratory, expiratory, and total cycle duration were used to compare respiratory function during quiet breathing, listening, and speech. Cross-correlation analyses of the respiratory movements of conversational partners provided an index of conversational synchrony. Inspiratory duration was found to be the most consistent and sensitive measure for discriminating quiet breathing from speech breathing. In the scripted dialog and spontaneous conversation conditions, respiratory kinematics changed during listening to more closely resemble speech, and systematic changes were observed in anticipation of turn-taking speech onset. For the breathing cycles immediately surrounding turn changes and simultaneously produced vocal events, the kinematic signals of conversational partners were strongly correlated. Results are discussed in the context of similar findings concerning conversational interactions and motor preparation for speech. PMID- 11218098 TI - Time estimation by adults who stutter. AB - In view of the fact that stuttering involves time pressure in communicative contexts, the aim of this investigation was to study the effect of stuttering on time estimation. Two matching groups of 47 adults each, one consisting of stutterers and the other of fluent speakers, estimated the duration of four verbal tasks-two that involved speaking and two that did not. Two methods of time estimation were used: production and reproduction. In production, participants were required to perform a task, terminating it when they felt that the specified interval had elapsed. In reproduction, participants were asked to estimate the duration of a task immediately after being stopped by the experimenter. The results reveal that the differences in time estimation between adults who stutter and fluent speakers were task dependent, with the stutterers estimating time less accurately on oral verbal tasks. The conversation task in particular highlighted the inaccuracy of their time estimation. Furthermore, severe stutterers estimated time less accurately than mild stutterers. The greatest inaccuracy was displayed by severe stutterers when estimating the time of an oral task by the production method. The results are discussed in terms of cognitive models based on attention to time, method measurement, and mental workload. Clinical implications are also suggested. PMID- 11218099 TI - An alternate MLU calculation: magnitude and variability of effects. AB - This study investigated the effect of removing elliptical question responses, imitative utterances, and single-word Yes/No responses before calculating MLU. Forty-seven language samples from preschoolers with and without language impairment were analyzed. Initial MLUs ranged from 2.0 to 6.5 across both groups. The alternate calculation procedures resulted in an average 18% increase in the MLU index, with individual samples increasing as little as 3% or as much as 49%. The magnitude of the effect was primarily related to discourse properties, although in the SLI group there were secondary relationships to language level and proficiency. The observed variation in the discourse properties of language samples makes the alternate MLU index attractive to clinicians and researchers. PMID- 11218100 TI - Production of English finite verb morphology: a comparison of SLI and mild moderate hearing impairment. AB - The performance on production of finite verb morphology of 19 children (ages 5;9 10;7) with mild-moderate sensorineural hearing impairment (SNH) was compared with that of 14 children with specific language impairment (SLI) (ages 7;2-10;9) and age-matched and language-matched control groups. On average, the SNH group outperformed the SLI group and was comparable to controls. However, a subset of the SNH group (n = 6) was impaired on one or both of these tasks. Degree of hearing loss or age of receiving hearing aids was not directly related to performance, but other language measures were. The subset was also significantly younger than the rest of the SNH group, suggesting that acquisition of finite verb morphology may be delayed in children with hearing impairments. Verb regularity had no effect on performance of any group, but word frequency and phonological complexity did exert an influence. The findings are discussed in relation to causative theories of SLI. PMID- 11218101 TI - Parental reports of spoken language skills in children with Down syndrome. AB - Spoken language in children with Down syndrome and in children in a normative group was compared. Growth trends, individual variation, sex differences, and performance on vocabulary, pragmatic, and grammar scales as well as MaxLU (maximum length of utterance) were explored. Subjects were 330 children with Down syndrome (age range: 1-5 years) and 336 children in a normative group (1;4-2;4 years;months). The Swedish Early Communicative Development Inventory-words and sentences (SECDI-w&s) was employed. Performance of children with Down syndrome at ages 3;0 and 4;0 was comparable with that of children in the normative group at ages 1;4 and 1;8 respectively. In comparison with children in the normative group of similar vocabulary size, children with Down syndrome lagged slightly on pragmatic and grammar scales. The early development proceeded in most cases with exponential or logistic growth. This stresses the great potential of early intervention. PMID- 11218102 TI - The role of sequential stream segregation and frequency selectivity in the perception of simultaneous sentences by listeners with sensorineural hearing loss. AB - The purpose of this study was to determine the role of frequency selectivity and sequential stream segregation in the perception of simultaneous sentences by listeners with sensorineural hearing loss. Simultaneous sentence perception was tested in listeners with normal hearing and with sensorineural hearing loss using sentence pairs consisting of one sentence spoken by a male talker and one sentence spoken by a female talker. Listeners were asked to repeat both sentences and were scored on the number of words repeated correctly in each sentence. Separate scores were obtained for the first and second sentences repeated. Frequency selectivity was assessed using a notched-noise method in which thresholds for a 1,000 Hz pure-tone signal were measured in noise with spectral notch bandwidths of 0, 300, and 600 Hz. Sequential stream segregation was measured using tone sequences consisting of a fixed frequency (A) and a varying frequency tone (B). Tone sequences were presented in an ABA_ABA_... pattern starting at a frequency (B) either below or above the frequency of the fixed 1,000 Hz tone (A). Initially, the frequency difference was large and was gradually decreased until listeners indicated that they could no longer perceptually separate the two tones (fusion threshold). Scores for the first sentence repeated decreased significantly with increasing age. There was a strong relationship between fusion threshold and simultaneous sentence perception, which remained even after partialling out the effects of age. Smaller frequency differences at fusion thresholds were associated with higher sentence scores. There was no relationship between frequency selectivity and simultaneous sentence perception. Results suggest that the abilities to perceptually separate pitch patterns and separate sentences spoken simultaneously by different talkers are mediated by the same underlying perceptual and/or cognitive factors. PMID- 11218103 TI - Beginning to talk at 20 months: early vocal development in a young cochlear implant recipient. AB - Early vocal development, consonant production, and spoken vocabulary were examined in a deaf toddler whose multichannel cochlear implant was activated at 20 months. Parent-child interactions were recorded before implantation and at monthly intervals during the first year of implant use. The child's utterances were classified according to developmental levels from the Stark Assessment of Early Vocal Development. The emergence of consonant types and consonant features were documented through listener transcription. Parent reports were used to monitor oral vocabulary growth. A large increase in canonical and postcanonical utterances was observed after 5 months of implant use, and these advanced prelinguistic forms were dominant in all subsequent recording sessions. Increases in the diversity of consonant types and features suggested that auditory information was used to increase phonetic diversity. It was reported that the child understood almost 240 words and spoke approximately 90 words after one year of implant experience. The combination of cochlear implantation at a young age, family support, and regular intervention appeared to facilitate efficient early vocal development and gains in spoken vocabulary. PMID- 11218104 TI - Nonmainstream dialect use and specific language impairment. AB - Most work looking at specific language impairment (SLI) has been done in the context of mainstream dialects. This paper extends the study of SLI to two nonmainstream dialects: a rural version of Southern African American English (SAAE) and a rural version of Southern White English (SWE). Data were language samples from 93 4- to 6-year-olds who lived in southeastern Louisiana. Forty were classified as speakers of SAAE, and 53 were classified as speakers of SWE. A third were previously diagnosed as SLI; the others served as either age-matched (6N) or language-matched (4N) controls. The two dialects differed in frequency of usage on 14 of the 35 coded morphosyntactic surface patterns; speakers of these dialects could be successfully discriminated (94%) from each other in a discriminant analysis using just four of these patterns. Across dialects, four patterns resulted in main effects that were related to diagnostic condition (SLI vs. 6N), and a slightly different set of four patterns showed effects that were related to developmental processes (4N vs. 6N). More interestingly, the surface characteristics of SLI were found to manifest in the two dialects in different ways. A discriminant function based solely on SAAE speakers tended to misclassify SWE children with SLI as having normal language, and a discriminant function based on SWE speakers tended to misclassify SAAE unaffected children as SLI. Patterns within the SLI profile that cut across the two dialects included difficulties with tense marking and question formation. The results provide important direction for future studies and argue for the inclusion of contrastive as well as noncontrastive features of dialects within SLI research. PMID- 11218105 TI - Relative treatment effects of two prelinguistic communication interventions on language development in toddlers with developmental delays vary by maternal characteristics. AB - This paper tests whether two prelinguistic communication interventions have a differential effect on productive and receptive language development 6 and 12 months after the end of treatment. We predicted that treatment effects on language development would vary as a function of pretreatment maternal responsivity or amount of mothers' formal education. Fifty-eight prelinguistic children with developmental delays and their mothers participated in the study. Children were randomly assigned to one of two staff-implemented treatments that were designed to increase intentional communication ability. Results confirmed the prediction that treatment effects on children's receptive and expressive language 6 and 12 months after the end of interventions vary as a function of pretreatment maternal responsivity and education level. PMID- 11218106 TI - A quantitative output-cost ratio in voice production. AB - A quantitative output-cost ratio (OCR) is proposed for objective use in voice production and is defined as the ratio of the acoustic output intensity to the collision intensity of the vocal folds. Measurement of the OCR is demonstrated in a laboratory experiment using 5 excised larynges and a transducer designed for use on human subjects. Data were gathered at constant fundamental frequency (150 Hz). Subglottal pressure was varied from 1.0 to 1.6 kPa, and glottal width at the vocal processes was varied from a pressed condition to a 2-mm gap. The OCR was plotted as a function of glottal width. With no vocal tract, the excised larynx experiments yielded a broad maxima in the OCR curves, across all subglottal pressure conditions, at about 0.6 mm. Computer simulations indicate that sharper maxima may occur when the influence of the vocal tract is taken into account. The potential clinical utility of the OCR is discussed for treatment of a wide range of voice disorders, including those involving both hyper- and hypoadduction. PMID- 11218107 TI - Durational, proportionate, and absolute frequency characteristic of disfluencies: a longitudinal study regarding persistence and recovery. AB - The main objective of this study was to investigate developmental aspects of disfluencies over time as stuttering persists or ameliorates for 2 groups of preschool age children who stutter. Results indicated that the frequency, type, and duration of disfluencies remained relatively constant instead of increasing as expected in the persistent group over a 3-year period. In contrast, the recovered group's initially higher frequency of disfluency decreased over time, as did their number of repetition units and proportion of disrhythmic phonations, while the duration of silent intervals between repetition units and proportion of monosyllabic word repetitions increased. PMID- 11218108 TI - Enhanced speechreading in deaf adults: can short-term training/practice close the gap for hearing adults? AB - This study investigated effects of short-term training/practice on group and individual differences in deaf and hearing speechreaders. In two experiments, participants speechread sentences with feedback during training and without feedback during testing, alternating 10 times over six sessions spanning up to 5 weeks. Testing used sentence sets balanced for expected mean performance. In each experiment, participants were adults who reported good speechreading and either normal hearing (n = 8) or severe to profound hearing impairments (n = 8). The experiments were replicates, except that in one participants received vibrotactile speech stimuli in addition to visible speech during training, testing whether vibrotactile speech enhances speechreading learning. Results showed that (a) training/practice did not alter the relative performance among individuals or groups; (b) significant learning occurred when training and testing were conducted with speechreading only (although the magnitude of the effect was small); and (c) there was evidence that the vibrotactile training depressed rather than raised speechreading scores over the training period. PMID- 11218109 TI - Effects of vowel height and vocal intensity on anticipatory nasal airflow in individuals with normal speech. AB - The purpose of this study was to determine the effects of vowel height and vocal intensity on the magnitude of anticipatory nasal airflow in normal speakers when producing vowel-nasal-vowel (VNV) sequences. Measurements of nasal and oral airflow were obtained from 15 men and 12 women with normal speech during production of the VNV sequences /ini/ and /ana/ at low, medium, and high intensity levels. Ratios of nasal to oral-plus-nasal airflow were calculated for the initial vowel of both utterances at each of the intensity levels. Analysis of variance (ANOVA) procedures indicated a significant main effect of intensity level and a significant vowel-by-sex interaction effect (p < .05) on the airflow ratios. Overall, the airflow ratio was reduced at high as compared to low intensity levels, regardless of sex of the speaker or vowel type. Female speakers exhibited greater airflow ratios during production of /ini/ than during productions of /ana/. Their airflow ratios were also greater during production of /ini/ than were those of male speakers. The results suggest that vocal intensity may affect velopharyngeal (VP) function in an assimilative nasal phonetic context. The results further suggest that anticipatory nasal airflow may be determined by the configuration of the oral cavity to a greater extent in women than in men. Theoretical and clinical implications are discussed. PMID- 11218110 TI - Perceptions of simulated stuttering and fluency. AB - This study explored multiple effects of listener perceptions of different levels of simulated stuttering and fluency. A single stuttered speech sample was modified to create four additional samples of stuttering and fluency. A sixth sample of a nonstuttered signal served as a comparative baseline. Each of 60 independent listeners made quantitative and qualitative perceptual judgments upon hearing only one of the six randomly assigned samples. Results showed a broad spectrum of qualitative and quantitative listener perceptions of the various levels of stuttering and fluency studied. Likert scale data revealed that listeners gave lower ratings to samples with increased levels of stuttering. Listener commentaries revealed fewer positive comments with increased levels of stuttering and distinctive preferences between two 0% samples of stuttering where only prosodic features were modified. Additionally, specific perceptions of speaker competency, perceived ease in reading a passage, general comfort listening, and perceived effort in understanding the story appear to affect the global perceptions of a speaker's communication. Implications of these findings are discussed. PMID- 11218111 TI - Phonetic inventory development in young cochlear implant users 6 years postoperation. AB - Increases in the phonetic inventories of a group of 9 children in the fifth and sixth years of experience with a cochlear implant are reported, extending a previous 4-year study (T. A. Serry & P. J. Blamey, 1999). Thirty-six out of 44 phones in Australian English reached the criterion of 50% correct in the conversational samples of 5 or more children. This level of performance corresponds to intelligible, but not completely natural, speech. The rate of improvement in the sixth year was slow, indicating a probable plateau in performance. The 8 phones that did not attain the 50% criterion in 5 or more children were /see text/. Potential reasons for the slow development or nondevelopment of these phones include very low frequency of occurrence for /see text/ and the perceptual and articulatory characteristics of /see text/. /see text/ is also subject to a high degree of allophonic variation in the fluent speech of normally hearing speakers, probably accounting for much of the variability in its articulation in the conversational samples. PMID- 11218112 TI - Relative kinematics of the rib cage and abdomen during speech and nonspeech behaviors of 15-month-old children. AB - Speech motor control emerges in the neurophysiologic context of widely distributed, powerful coordinative mechanisms, including those mediating respiratory function. It is unknown, however, whether developing children are able to exploit the capabilities of neural circuits controlling homeostasis for the production of speech and voice. Speech and rest breathing were investigated in eleven 15-month-old children using inductance plethysmography (Respitrace). Rib cage and abdominal kinematics were studied using a time-varying correlational index of thoracoabdominal coupling (i.e., reflecting the synchrony of movement of the rib cage and abdomen) as well as simple classification of the moment-to moment kinematic relationship of these two functional components (i.e., concurrent expansion or compression, or oppositional movement). Results revealed markedly different patterns of movement for rest breathing and speech breathing, although within types of vocalization (nonspeech vocalization, babbling, true word production) no differences were apparent. Whereas rest breathing was characterized by tight coupling of rib cage and abdominal movement (average correlation coefficients usually exceeded .90), speech breathing exhibited weak coupling (the correlation coefficient ranged widely, but averaged about .60). Furthermore, speech production by these toddlers included the occurrence of both rib cage and abdominal paradoxing, which are observed infrequently in adult speakers. These results fail to support the suggestion that speech emerges from the extant coordinative organization of rest breathing. Rather, even in its earliest stages breathing for speech and voice exhibits kinematic properties distinct from those of other observed behaviors. PMID- 11218113 TI - Morphological analyses of the human tongue musculature for three-dimensional modeling. AB - Skilled movements of the tongue in speech articulation reflect complex formation of the tongue musculature, although its description in the anatomical literature is rather limited for developing a realistic computational model of the tongue. This study presents detailed descriptions of the muscular structure of the human tongue based on macroscopic and microscopic observations and provides three dimensional schemata of the tongue musculature. Histologic examination revealed that the tongue consists of five strata, stacked along the courses of the fibers of the genioglossus muscle in proximal-distal directions. This stratum structure exists in the entire tongue tissue, indicating that the lingual musculature can be divided into the inner and outer regions. The former consisted of the "stem" and "core," and the latter of the "cover" and "fringe." In gross dissection, the tongue was cut into wedge-like blocks along the course of the genioglossus muscle to examine muscle fiber arrangement. Using this approach, it was determined that serial repetitions of "structural units" composed the inner musculature of the tongue. Each unit consisted of a pair of thin muscle fiber laminae; one was composed of the genioglossus and vertical muscles, and the other of the transverse muscle. In the apex, the laminae lacked the fibers of the genioglossus. These findings have been incorporated in three-dimensional schemata of the tongue musculature. PMID- 11218114 TI - Theoretical study of the accuracy of the elution by characteristic points method for bi-langmuir isotherms. AB - The bi-Langmuir equation has recently been proven essential to describe chiral chromatographic surfaces and we therefore investigated the accuracy of the elution by characteristic points method (ECP) for estimation of bi-Langmuir isotherm parameters. The ECP calculations was done on elution profiles generated by the equilibrium-dispersive model of chromatography for five different sets of bi-Langmuir parameters. The ECP method generates two different errors; (i) the error of the ECP calculated isotherm and (ii) the model error of the fitting to the ECP isotherm. Both errors decreased with increasing column efficiency. Moreover, the model error was strongly affected by the weight of the bi-Langmuir function fitted. For some bi-Langmuir compositions the error of the ECP calculated isotherm is too large even at high column efficiencies. Guidelines will be given on surface types to be avoided and on column efficiencies and loading factors required for adequate parameter estimations with ECP. PMID- 11218116 TI - Automated normal-phase preparative high-performance liquid chromatography as a substitute for flash chromatography in the synthetic research laboratory. AB - An automated normal-phase preparative HPLC system was developed in order to omit time-consuming flash column chromatography in the synthetic research laboratory. The system is equipped with steel columns packed with spherical 12 microm silica and is able to separate samples in a range of 0.1-10 g depending on the column diameter and chromatographic problem. It was designed to be used as an open access instrument in the research department. The general users select from binary gradient programs after running an analytical TLC with the raw product. The HPLC instrument was fully controlled by the Chromeleon software from Dionex. A Gilson 215 robot served as injector/collector. PMID- 11218115 TI - Characterizing the performance of industrial-scale columns. AB - The performance of a large commercial chromatographic column was investigated using a short pulse of a tracer and an extension of the reverse-flow technique. This technique permits separate determination of the unavoidable irreversible microscopic processes and the reversible effects of flow maldistribution, and allows for the separation of flow maldistribution in the flow distributors from flow maldistribution inside the packed bed. This analysis was performed on a 0.44 m Millipore IsoPak column using Cellufine GC 700, cellulosic-based media with an average particle diameter of 75 microm, for the stationary phase. The column efficiency was quantified by analysis of the effluent curve from a short pulse of a 5% aqueous acetone tracer. The study examined behavior of beds of different lengths (10-24 cm) and beds packed from different slurry concentrations (10-75% v/v). The slurry-packed columns were very uniform, and no significant macroscopic flow maldistribution was observed inside the column. The observed bed plate heights conformed to the predictions of available one-dimensional continuum models. Dispersion in the flow distributors was significant, corresponding to 15 25% of the intracolumn dispersion when the full 24 cm available bed length was used and a proportionally larger increase for shorter bed lengths. Thus, the headers are shown to produce a significant increase in the observed plate height. PMID- 11218117 TI - Comparison of chromatographic ion-exchange resins. II. More strong anion-exchange resins. AB - A comparative study was performed on strong anion exchangers to investigate the pH dependence, titration curves, efficiency, binding strength, particle size distribution, and static and dynamic capacity of the chromatographic resins. The resins tested included Q Sepharose XL, UNO Q-1, Poros 50 HQ, Toyopearl QAE 550c, Separon HemaBio 1000Q, Q-Cellthru Bigbeads Plus, Q Sepharose HP and Toyopearl SuperQ 650s. Testing was performed with five different proteins: anti-Factor VII monoclonal antibody (immunoglobulin G), aprotinin, bovine serum albumin, lipolase and myoglobin. The dependence of pH on retention varies from generally low to very high for proteins with a low isoelectric point (pl). An unexpected binding at pH 7-8 of aprotinin with pI >11 was observed on Separon HemaBio 1000Q. No link between pH dependence on retention and titration curves of the different resins was observed. Efficiency results show the expected trend of higher dependence of the plate height with increasing flow-rate of soft resins compared to resins for medium- and high-pressure operation. No or a very small difference in particle size distribution was obtained between new and used resins. Binding to anion exchange resins as a function of ionic strength varies to some extent depending on the specific protein. Generally, binding and elution at high salt concentration may be performed with Q Sepharose XL, Toyopearl QAE 550c, Q Sepharose HP and Poros 50 HQ, while binding and elution at low salt concentration may be performed with Q-Cellthru Bigbeads Plus. A very high binding capacity was obtained with Q Sepharose XL. Comparison of static capacity and dynamic capacity at 10% breakthrough shows approx. 50-80% utilization of the total available capacity during chromatographic operation. A general good agreement was obtained between this study and data obtained by the suppliers. The results of this study may be used for selection of resins for testing in process development. PMID- 11218118 TI - Advances in process chromatography gradient elution using binary linear gradients. AB - A number of chromatography techniques utilize mobile phase gradients with changing buffer concentration to effect separation. At process scale the majority of gradients are stepwise or isocratic. There are a number of instances where process performance or economics indicate that linear gradients would deliver better theoretical performance. However, to date this process advantage has not been implemented due to concerns about the accuracy, reliability or reproducibility of equipment used to produce linear changes in gradient composition. In this manuscript, recent developments in simple feedforward control and data from the resultant process-scale performance are presented. Information is provided on the practical heuristics underlying the control strategy. The data presented in this paper illustrate how the feedforward control strategy has been implemented on a commercial system to achieve better than +/- 2% accuracy of process-scale linear gradients. PMID- 11218119 TI - Performance comparison of suspended bed and batch contactor chromatography. AB - In some applications, the purification and recovery of biomolecules is performed via a cascade of batch adsorption and desorption stages using agitated contactors and related filtration devices. Suspended bed chromatography is a recent process scale innovation that is applicable to these separations. This hybrid technique exploits the benefits of combining batch adsorption in an agitated contactor with elution in an enclosed column system. To some extent, the process is similar to batch contactor chromatography but can be fully contained and significantly quicker. The process has two steps; first the fluid containing the sample is mixed with the adsorbent in a stirred tank. Second, the slurry suspension is transferred directly into a specialized column, such as an IsoPak column. The media with the adsorbed product is formed as a packed bed, whilst the suspension liquid is passed out of the column. The product is then eluted from the packed bed utilizing standard column-chromatography techniques. The performance of the suspended bed and the agitated contactor operations are demonstrated both by full scale experimental results and process simulations. The purification of ovalbumin from a hen-egg white feedstock by anion-exchange chromatography was used as a case study in order to prove the concept. With the availability of both pump packed systems and shear-resistant media, suspended bed chromatography is a better alternative for a range of applications than the traditional batch separations using agitated contactors. PMID- 11218120 TI - Control method for integrity of continuous beds. AB - Monoliths are considered to be the latest version of stationary phases for protein chromatography. They are now becoming popular since they exhibit reduced peak broadening due to low mass transfer resistances. A weak point of monoliths may be an inhomogeneous bed, especially when charged groups are present during co polymerization. This becomes apparent when a protein solution is loaded onto such a monolith. A biphasic breakthrough curve differing from the sigmoidal-shaped one, is observed. Two error functions were used to approximate the breakthrough curve. From these parameters an estimate of the fraction of flow passing through the homogeneously packed part of the bed as well as the inhomogeneously one was derived. This flow pattern was also confirmed by perfusing ferritin through an inhomogeneous monolith and comparing it to an intact one. Electron microscopy and mercury porosimetry did not indicate any abnormalities in the bed. PMID- 11218121 TI - Modification of a commercial chiral stationary phase influences on enantiomer separations using simulated moving bed chromatography. AB - Chromatographic enantiomer separations using high-performance chromatography and the simulated moving bed (SMB) principle have become a practically useful method for obtaining optical isomers. The carbamate derivatives of amylose coated onto silica particles are very effective chiral stationary phases (CSPs). Several lots of Chiralpak AS, and its successor, Chiralpak AS-V, were compared by laser diffraction, microscopic imaging and pulse injections with increasing amounts of various racemates in order to determine the loading capacity and the competitive adsorption isotherms. Software simulations allowed to assess the possible effects due to the observed variations between the CSPs on the performance of a pilot SMB unit. The obtained results were verified by two multi-kilogram separations performed under current good manufacturing principles (cGMP) guidelines employing the two CSPs. The results of the two production runs are discussed in the light of the recently introduced "triangle theory" which allows to account for the overload conditions prevailing under preparative chromatographic conditions and to predict optimal operating conditions. Under optimized conditions the enantiomer separation of 1.4 kg racemate/kg stationary phase per day with purities >99.6% for the target enantiomer have been achieved. PMID- 11218122 TI - Frontal analysis method to determine competitive adsorption isotherms. AB - In order to design and to optimise preparative separations, the knowledge of the underlying thermodynamic functions, i.e., the adsorption isotherms, is the most essential information. Usually these functions cannot be predicted and various methods have been suggested to determine them experimentally. In particular, dynamic methods are attractive regarding time requirements and reliability. Frontal analysis (FA) is frequently applied to measure single solute isotherms. The theoretical background of this method is offered by the classical equilibrium theory of adsorption. Although this theory also explains the shape of multicomponent breakthrough curves, FA is only seldom applied to determine competitive isotherms. In this work FA was used to measure adsorption isotherms of three components as single solutes and in binary and ternary mixtures in a reversed-phase system. The obtained equilibrium data were correlated using the competitive Langmuir isotherm equation, a bi-Langmuir model, the ideal adsorbed solution theory and the real adsorbed solution theory. No substantial improvement of the predictions was achieved using the more complex models instead of the most simple Langmuir model. PMID- 11218123 TI - Coupling of simulated moving bed chromatography and fractional crystallisation for efficient enantioseparation. AB - An optimised coupling of liquid chromatography and fractional crystallisation is suggested for efficient enantioseparation. As a first stage, a chromatographic separation, preferably simulated moving bed (SMB) chromatography, is applied to achieve an enantiomeric enrichment sufficient for a subsequent crystallisation. First results of the experimental and modelling work for the model system (+)-/( )-mandelic acid in an aqueous solution are described. Chromatographic investigations involve the estimation of adsorption isotherms on a suitable chiral stationary phase and the simulation and optimisation of a corresponding SMB process. From the ternary phase diagram measured for the (+)-/(-)-enantiomer/ solvent system, the conditions required to crystallise a pure enantiomer from an asymmetric mixture can be derived. The productivity gains achievable from the combined process compared to the application of chromatography alone are discussed. PMID- 11218124 TI - Calculation of partition coefficient and hydrophobic moment of the secondary structure of lysozyme. AB - A method that permits a semiquantitative estimate of the partitioning of any solute between any two media is presented. As an example, the partition coefficients and hydrophobic moment of the secondary structure of lysozyme are calculated. Program GSCAP is written as a version of Pascal's solvent-dependent conformational analysis (SCAP) program. The dipole moments calculated for the helices are trebled with respect to that for the sheet. For helices, the main contribution to the water-accessible surface area is the hydrophobic term, while the hydrophilic part dominates in the sheet. Molecular globularity and the three studied partition coefficients differentiate between helices and sheet. PMID- 11218126 TI - Use of ion-exchange chromatography and hydrophobic interaction chromatography in the preparation and recovery of polyethylene glycol-linked proteins. AB - Cation- and anion-exchange chromatography can be used to purify a polyethylene glycol-linked protein dimer (PEG dimer) made with M, 20 000 PEG bis-vinylsulfone, even when there are no net charge differences between the components that are being separated. The retention time on ion-exchange generally is inversely proportional to the PEG:protein ratio (on a mass basis). One of the biggest challenges in developing the process for making this PEG dimer was the quality of the PEG linker. Reversed-phase HPLC can be used to determine both size heterogeneity and the degree of end-group activation of Mr 20 000 PEG bis vinylsulfone. In addition, we have found that hydrophobic interaction chromatography can be used make more size homogeneous preparations of Mr 20000 PEG bis-vinylsulfone, which significantly increased the recovery of the PEG dimer. PMID- 11218125 TI - Direct isolation of monoclonal antibodies from tissue culture supernatant using the cation-exchange cellulose Express-Ion S. AB - The chromatography of the murine hybridoma cell C595/102 culture supernatant expressing the therapeutic monoclonal antibody C595, on the cation-exchange cellulose Whatman Express-Ion Exchanger S has been investigated. Initial method scouting studies using purified C595 in 1-ml mini columns demonstrated that binding capacity and binding efficiency were dependent not only on decreasing pH but also on the buffer salts used to prepare the mobile phase. Under optimised conditions of 0.1 M sodium acetate buffer, pH 5.0, we were able to separate purified C595 from BSA, the major contaminant in tissue culture fluid. Under these conditions immunoreactive C595 could be isolated directly from tissue culture supernatant. A scale-down study was carried out using a 25-ml column operated at a flow-rate of 150 cm/h which also yielded purified immunoreactive antibody. This procedure should now be suitable for scale-up. PMID- 11218127 TI - Continuous separation of green fluorescent protein by annular chromatography. AB - The concept of annular chromatography was tested by separation of a real protein solution used in biotechnology. Green fluorescent protein was expressed in S. cerevisiae and the extract was continuously separated by a pressurized annular chromatograph packed with a Superdex 200 prep grade size-exclusion chromatography medium. Purity was checked by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blotting and fluorescent intensity. The continuous mode was compared to batchwise operation. Under the assumption that equivalent fractions are collected, both modes are comparable. PMID- 11218128 TI - Comparison of hydrophobic charge induction chromatography with affinity chromatography on protein A for harvest and purification of antibodies. AB - Efficient harvest and recovery of high-purity monoclonal antibodies was achieved using hydrophobic charge induction chromatography (HCIC). Both simple and complex feedstocks were studied, including protein-free cell culture supernatant and the clarified/concentrated milk of transgenic goats. Viral clearance studies demonstrated a 4-log reduction of MVM virus (minute virus of mice), along with substantial reduction of DNA content. Sorbent characterization studies confirmed that HCIC is based on the pH-dependent behavior of a dual-mode, ionizable ligand. Binding, based on hydrophobic interaction, was achieved under near-physiological conditions, and in the absence of lyotropic salt. Desorption was accomplished under mild conditions--pH 4.0. At this pH, both ligand and antibody carry a net positive charge, and desorption occurs on the basis of electrostatic charge repulsion. pH-based control of chromatographic function was demonstrated. Chromatography on this antibody-selective HCIC sorbent was evaluated as a cost effective, process-compatible alternative to affinity chromatography protein A sorbents. PMID- 11218129 TI - Separation of steroid compounds by overloaded preparative chromatography with precipitation in the fluid phase. AB - In order to gain a commercially acceptable yield compared to the adsorption capacity of the column, a rather large amount of sample is separated with preparative chromatography. During the competitive adsorption of the sample components, the species adsorbing better can force the rest out of the adsorbent phase. As a consequence, the concentrations of the later components may increase in the fluid phase to a level that those species start to precipitate. A mathematical model which takes the precipitation and dissolution into consideration is presented in this paper. Data calculated by this model are compared to that we obtained by using a previous mathematical model as well as the experimental results gained by a laboratory scale separation of steroid compounds on an organic polymer adsorbent. The equilibrium adsorption-desorption and equilibrium precipitation-dissolution is the first approximation of the complicated process mentioned above. In our next publication we are to extend the model with kinetic terms belonging to adsorption-desorption and precipitation dissolution process respectively. PMID- 11218131 TI - Flow microcalorimetric measurements for bovine serum albumin on reversed-phase and anion-exchange supports under overloaded conditions. AB - Heat of adsorption data using flow microcalorimetry is reported for the adsorption of bovine serum albumin (BSA) on C18 and C4 chromatographic supports. Exothermic heats were obtained in all cases. Data for the effect of salt indicate that conformational changes in adsorbed protein appear to be greatest in the absence of salt. Also, the specific surface area of the support was found to influence behavior more strongly than the length of the carbon ligand. Heats of adsorption of BSA on an ion-exchange support were also measured. Endothermic heats were obtained in all cases. The data indicate that the observed heat effects may be strongly influenced by the release of water from the surface. PMID- 11218130 TI - Purification of adipoyl-7-amino-3-deacetoxycephalosporanic acid from fermentation broth using stepwise elution with a synergistically adsorbed modulator. AB - Multicomponent adsorption data of a fermentation broth containing adipoyl-7-amino 3-deacetoxycephalosporanic acid (adipoyl-7-ADCA), a cephalosporin precursor for 7 ADCA, and two key impurities, alpha-hydroxyadipoyl-7-ADCA and alpha-aminoadipoyl 7-ADCA were obtained from batch equilibrium and frontal chromatography tests. Amberlite XAD-1600 was chosen as the resin. A rate model was applied to simulate the chromatograms. An alkaline buffer, which by itself has no affinity for the resin, was used as the eluent. The widely used reversed-phase modulator model is inaccurate in explaining the stepwise elution data. A new model, the induced competition model, has been developed to account for apparent retention of the buffer in the presence of adsorbed species. Close agreement between the simulations and the data was achieved with the new model. PMID- 11218132 TI - Description of adsorption equilibria in liquid chromatography systems with binary mobile phases. AB - Adsorption of some simple compounds from pure and mixed solvents and of some solvents from mixed binary solvent mixtures on columns used in normal-phase, aqueous-organic and non-aqueous liquid chromatography was investigated. The distribution of the compounds between the liquid and the stationary phase is affected by the composition of the solvent mixture. Although preferential sorption of stronger solvents can often be described by the Langmuir isotherm, significant deviations are observed in some systems. A model was suggested accounting for the deviations from Langmuir isotherm by association on already adsorbed molecules. In most systems studied in this work, a simple competitive Langmuir isotherm did not provide a good fit to the experimental distribution data from mixed solvents when competition between the solute and the strong solvent for the adsorption sites was considered. A competitive isotherm taking into account possible association of solute on its own already adsorbed molecules and on the adsorbed molecules of strong solvent improves the fit to the experimental distribution data and enables description of the distribution data in dependence on the concentration of the strong solvent in mixed solvents in normal-phase, aqueous-organic and non-aqueous reversed-phase systems. Even though we need more data to prove the validity of the present model, we observe a good qualitative agreement of the experimental isotherm coefficients with the relative strength of the interactions expected in various chromatographic systems employing mixed solvents. PMID- 11218134 TI - Effect of the homogeneity of the column set on the performance of a simulated moving bed unit. I. Theory. AB - Although it is impossible to manufacture identical columns for use in a simulated moving bed (SMB) process, theoretical studies assume that all the columns in an SMB unit have identical characteristics. In practice, calculations in modeling and optimization studies are made with the average values of each column parameter set. In this report, the effects on SMB process performance caused by column-to-column fluctuations of the parameters are discussed. As a first step, we show how the differences in porosity of the columns may be taken into account with a revised set of separation conditions. Reductions in the purity of the extract and the raffinate streams are quantitatively related to the column-to column fluctuations of the retention times of the two components arising from these porosity differences. For the sake of simplicity, the discussion first addresses the case of a four-column SMB operating under linear conditions. Then, the scope is extended to the cases of SMB units incorporating several columns in each section and to SMB units operating under nonlinear conditions. PMID- 11218133 TI - Pore network modelling: determination of the dynamic profiles of the pore diffusivity and its effect on column performance as the loading of the solute in the adsorbed phase varies with time. AB - A three-dimensional pore network model for diffusion in porous adsorbent particles was employed in a dynamic adsorption model that simulates the adsorption of a solute in porous particles packed in a chromatographic column. The solution of the combined model yielded the dynamic profiles of the pore diffusion coefficient of beta-galactosidase along the radius of porous ion exchange particles and along the length of the column as the loading of the adsorbate molecules on the surface of the pores occurred, and, the dynamic adsorptive capacity of the chromatographic column as a function of the design and operational parameters of the chromatographic system. The pore size distribution of the porous adsorbent particles and the chemistry of the adsorption sites were unchanged in the simulations. It was found that for a given column length the dynamic profiles of the pore diffusion coefficient were influenced by: (i) the superficial fluid velocity in the column, (ii) the diameter of the adsorbent particles and (iii) the pore connectivity of the porous structure of the adsorbent particles. The effect of the magnitude of the pore connectivity on the dynamic profiles of the pore diffusion coefficient increased as the diameter of the adsorbent particles and the superficial fluid velocity in the column increased. The dynamic adsorptive capacity of the column increased as: (a) the particle diameter and the superficial fluid velocity in the column decreased, and (b) the column length and the pore connectivity increased. In preparative chromatography, it is desirable to obtain high throughputs within acceptable pressure gradients, and this may require the employment of larger diameter adsorbent particles. In such a case, longer column lengths satisfying acceptable pressure gradients with adsorbent particles having higher pore connectivity values could provide high dynamic adsorptive capacities. An alternative chromatographic system could be comprised of a long column packed with large particles which have fractal pores (fractal particles) that have high pore connectivities and which allow high intraparticle diffusional and convective flow mass transfer rates providing high throughputs and high dynamic adsorptive capacities. If large scale monoliths could be made to be reproducible and operationally stable, they could also offer an alternative mode of operation that could provide high throughputs and high dynamic adsorptive capacities. PMID- 11218135 TI - Application of equilibrium theory to ternary moving bed configurations (four+four, five+four, eight and nine zones) I. Linear case. AB - In this article, different ternary moving bed configurations are studied by determining the working flow-rates of the equivalent true moving bed at the low solvent consumption point using equilibrium theory. This method has been applied for linear adsorption isotherms. The simulated moving bed flow-rates can then be calculated and a final comparison between the performances of each process is given based upon two different objective functions. PMID- 11218136 TI - Application of the equilibrium theory to ternary moving bed configurations (4+4, 5+4, 8 and 9 zones). II. Langmuir case. AB - In this article, the overall methodology used to determine the working flow-rates of a true moving bed (TMB) processing langmuirian isotherms compounds is explained. Then it is applied to different ternary configurations (4+4, 5+4, 8 or 9 zones TMB) in order to characterize their performances. Finally the results obtained on all the configurations are compared on a given example. This comparison allows the choice of the more suitable configuration to be used for a given set of compounds. PMID- 11218137 TI - Determination of lewisite oxide in soil using solid-phase microextraction followed by gas chromatography with flame photometric or mass spectrometric detection. AB - A rapid, sensitive, and convenient method is described for determining Lewisite oxide in soil. Samples are initially fortified with phenylarsine oxide (surrogate), then both species are extracted using ascorbic acid solutions containing 1,3-propanedithiol (derivatizing reagent). The corresponding filtered supernatant is sampled using a solid-phase microextraction fiber. Collected analytes are thermally desorbed in a heated gas chromatographic inlet, separated using fused-silica capillary columns ("primary" and "confirmatory"), and detected with either a mass spectrometric (selected ion monitoring mode) or flame photometric (sulfur-selective mode) detector. Two independent statistically unbiased procedures were used to evaluate the detection limit for Lewisite oxide; the values range between 0.1 and 0.5 microg g(-1) soil. PMID- 11218138 TI - Application of on-site solid-phase microextraction in aquatic dissipation studies of profoxydim in rice. AB - The application of a manual operated solid-phase microextraction (SPME)-HPLC interface is discussed for the analysis of thermally labile analytes in aqueous matrices. The technique has been applied on-site at a flooded rice field to demonstrate its potential for real time extraction of the herbicide profoxydim. Thus, compounds which would otherwise easily degrade in the aqueous matrices within hours or days could be determined more accurately. The fibers were shipped back to the laboratory with express delivery where the target analyte was desorbed from the fiber and determined by HPLC-UV analysis. The SPME method was characterized by significant ruggedness where conventional techniques such as liquid-liquid extraction and solid-phase extraction require additional shipping and handling costs and time-consuming multiple sample preparation steps. In general, any delay in shipping the aqueous samples to the laboratory has the potential for sample degradation and a loss in accuracy when using non on-site extraction techniques. Fifty microm Carbowax-templated resin coatings were most suitable for coupling SPME to HPLC in order to achieve a high sensitivity for polar analytes. The SPME technique was characterized by a good sensitivity and a precision less than 10% RSD. The SPME-LC-UV method was linear over at least three orders of magnitude while achieving a limit of detection in the lower microg/l range. The on-site SPME method has shown significantly increased accuracy. Profoxydim was determined at concentrations of ca. 180 microg/l 3 h after an application on a flooded bare soil field. PMID- 11218139 TI - Combining membrane extraction with mobile gas chromatography for the field analysis of volatile organic compounds in contaminated waters. AB - A mobile gas chromatographic device (Airmobtx HC 1000 monitor manufactured by Airmotec, Germany), originally designed for the analysis of benzene, toluene, ethylbenzene and xylenes (BTEX) in air, was connected to a flow cell for dynamic membrane extraction. Volatile organic compounds (VOCs) diffuse out of a water stream through a hollow fibre, are enriched onto sorption tubes integrated in the mobile device, and are then thermally desorbed and analysed by gas chromatography flame ionisation detection. Battery operation of the device enables continuous on site analysis of VOCs. Influences of the water flow-rate on system response and memory effects were investigated. The linear range of the method depends on the flow-rate of the water sample and did not exceed two orders of magnitude. The detection limits for trichloroethene, chlorobenzene and the BTEX compounds were found to be between 0.1 and 1.0 microg/l using a water flow-rate of 30 ml/min. Dynamic membrane extraction combined with the mobile gas chromatographic device was used for the on-site analysis of contaminated waters in the area of Leipzig. PMID- 11218140 TI - Preparation and applications of polypyrrole films in solid-phase microextraction. AB - Polypyrrole (PPY) and poly-N-phenylpyrrole (PPPY) films were prepared and applied for solid-phase microextraction (SPME). The extraction properties of the new films to volatile organic compounds were examined using an SPME device coupled with GC-flame ionization detection. A PPY-coated capillary was applied for in tube SPME to evaluate its extraction efficiency towards less volatile compounds and ionic species. The porous surface structures of the films, revealed by scanning electron microscopy, provided high surface areas and allowed for high extraction efficiency. Compared with commercial SPME stationary phases, the new phases showed better selectivity and sensitivity toward polar, aromatic, basic and anionic compounds, due to their inherent multifunctional properties. In addition, PPY and PPPY films showed different selectivity to various groups of compounds studied, indicating that the selectivity of the films could be modified by introducing a new functional group (phenyl in PPPY) into the polymer. For in tube SPME, the PPY-coated capillary showed superior extraction efficiency to commercial capillaries for a variety of compounds, demonstrating its potential applications for a wide range of analytes when coupled with HPLC. The sensitivity and selectivity of the films for SPME could be tuned by changing the film thickness. These results are in line with both the theoretical expectations and the results obtained by other methods, which indicate not only that PPY films can be used as new stationary phases for SPME. but also that SPME method may provide an alternative tool for studying materials like polypyrrole. PMID- 11218141 TI - Detection of the cyclic nitramine explosives hexahydro-1,3,5-trinitro- 1,3,5 triazine (RDX) and octahydro- 1,3,5,7-tetranitro- 1,3,5,7-tetrazine (HMX) and their degradation products in soil environments. AB - The cyclic nitramine explosives hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazine (HMX) were examined in field and microcosm soil samples to determine their patterns of degradation and environmental fates. A number of analytical techniques, including solid-phase microextraction with on-fiber derivatization, gas chromatography-mass spectrometry, gas chromatography with electron-capture detection, liquid chromatography-mass spectrometry, and micellar electrokinetic chromatography were required for the analyses. Two different classes of intermediates were detected, both of which lead ultimately to the formation of nitrous oxide (N2O) and carbon dioxide (CO2). The first class was identified as the nitroso derivatives formed by the sequential reduction of -NO2 functional groups. The second class of intermediates, which was favored at higher humidities and in the presence of anaerobic sludge amendments, consisted of ring cleavage products including bis (hydroxymethyl)-nitramine and methylenedinitramine. Rye-grass (Lolium perenne) present in field samples was found to extract and accumulate HMX from soil without further degradation. In all cases (excepting the plant samples), the indigenous microbes or amended domestic anaerobic sludge consortia degraded the cyclic nitramine explosives eventually to produce N2O and CO2. PMID- 11218142 TI - Development and application of immunoaffinity chromatography for the determination of the triazinic biocides in seawater. AB - The development of an immunoaffinity chromatography (IAC) procedure for the selective extraction of the anti-fouling agent Irgarol 1051 [2-(tert.-butylamino) 4-(cyclopropylamino)-6-(methylthio)-1,3,5-triazine] from seawater is described. The anti-Irgarol 1051 antibodies were covalently bound to agarose-based beads support. IAC column capacities were higher than 400 ng and ethanol-water (70:30) was selected as eluting mixture. After percolation of 250 ml of water sample containing Irgarol 1051 at environmental levels (ng l(-1) ), the breakthrough volume was still not achieved. Other triazine herbicides percolated through the IAC column showed good recoveries. Thus, this IAC procedure may be useful to extract related compounds. The developed IAC column was applied to real seawater samples and compared with RP-C18 cartridges. The limit of detection (LOD) reached by using the IAC procedure was twenty times lower than the LOD achieved by the RP C 18 cartridges using the same detection system. Irgarol 1051 was detected at ng l(-1) levels in the Barcelona marina (northwestern Mediterranean Sea). An acceptable correlation between enzyme-linked immunosorbent assay and gas chromatography with nitrogen-phosphorus detection was observed, thus analysis of Irgarol 1051 can be performed by either one of the methods. In this work, further confirmation of the analyte identity for real samples was accomplished by gas chromatography-electron impact mass spectrometry. PMID- 11218143 TI - Alkyl diol silica: restricted access pre-column packings for fast liquid chromatography-integrated sample preparation of biological fluids. AB - A silica-based pre-column packed with a 'restricted access material' was used for fully automated solid-phase extraction of drugs and metabolites from untreated biological fluids via a simple valve-switching method. The bifunctional sorbent employed, alkyl diol silica, is characterised by a different chemical modification of the outer surface (diol groups) and the pore surface of the particles (alkyl chains: C4, C8 or C18). This allows for a fast and efficient clean-up of complex biological samples, such as blood, serum, urine or milk, with exclusion of the macromolecular matrix (proteins, nucleic acids) in less than 1.5 min. PMID- 11218144 TI - Miniaturized solid-phase extraction with resin disks. AB - The properties and advantages of membrane disks for solid-phase extraction (SPE) are described. Miniaturization is a trend in SPE, as well as chemical analysis in general. A semimicro method is reviewed in which an extraction disk 4 mm in diameter is used for SPE. Even smaller scale separations are possible with a device in which a membrane 0.7 mm in diameter was incorporated into the needle of a 50-micro syringe. Aqueous samples containing 10 ppb of eight substituted benzenes were passed through the miniaturized-SPE syringe automatically using a single-syringe infusion pump. Elution volumes of 5 microl provided 500-fold concentrations and delivered average recoveries greater than 90% and an average relative standard deviation (RSD) of 4.6% for the analytes. Direct injection of the 5 microl eluate from the miniaturized-SPE syringe into a gas chromatograph also produced average recoveries greater than 90% and an average RSD of 6.2%. PMID- 11218145 TI - Liquid-phase microextraction and capillary electrophoresis of citalopram, an antidepressant drug. AB - A newly developed disposable device for liquid-phase microextraction (LPME) was evaluated for the capillary electrophoresis (CE) of the antidepressant drug citalopram (CIT) and its main metabolite N-desmethylcitalopram (DCIT) in human plasma. CIT and DCIT were extracted from 1 ml plasma samples through hexyl ether immobilised in the pores of a porous polypropylene hollow fibre and into 25 microl of 20 mM phosphate buffer (pH 2.75) present inside the hollow fibre (acceptor phase). Prior to extraction, the samples were made strongly alkaline in order to promote LPME of the basic drugs. Owing to the high ratio between the volumes of sample and acceptor phase, and owing to high partition coefficients, CIT and DCIT were enriched by a factor of 25 to 30. In addition, sample clean-up occurred during LPME since salts, proteins and the majority of endogenic substances were unable to penetrate the hexyl ether layer. Since the extracts were aqueous, they were injected directly into the CE instrument. Limits of quantification (S/N= 10) for CIT and DCIT in plasma were 16.5 ng/ml and 18 ng/ml respectively, while the limits of detection (S/N=3) were 5 ng/ml and 5.5 ng/ml respectively. This enabled CIT (and DCIT) to be analysed within the therapeutic range by LPME-CE and detection limits were comparable with previously reported HPLC methods. PMID- 11218146 TI - In situ derivatisation using pressurized liquid extraction to determine phenols, sterols and carboxylic acids in environmental samples and microbial biomasses. AB - Pressurized liquid extraction was combined with in-situ derivatisation to extract polar analytes such as phenols (including chlorophenols) sterols and carboxylic acids from environmental and microbial samples. This one-step protocol uses acetic anhydride as an acetylation agent, N,O bis(trimethylsilyl)trifluoroacetamide (BSTFA) as an silylation agent, and boron trifluoride-methanol, phenyltrimethyl ammoniumhydroxide and trimethyl sulfoniumhydroxide as methylation agents. It results in faster extraction rates and better or comparable extraction efficiencies when compared to classical approaches. The addition of a silylation agent also facilitates the extraction kinetics of analytes not accessible to silylation (e.g. polycyclic aromatic hydrocarbons or alkylbenzenes). This may be attributed to a dissociative action of the agent to weaken analyte-matrix interactions. PMID- 11218147 TI - Leptin and leptin binding activity in the preovulatory follicle of polycystic ovary syndrome patients. AB - To investigate the clinical importance of leptin's intraovarian effects, we studied the concentration of leptin and leptin binding activity in the plasma and in the follicular fluid of PCOS patients (n=20; median BMI: 27.1 kg/m2, range 19.7-36.3) undergoing controlled ovarian stimulation with long-term GnRH agonist, recombinant FSH, and in vitro fertilization. Follicular fluid and blood samples were collected during follicle aspiration for IVF. Total leptin concentration was measured by radioimmunoassay, and specific leptin binding activity was accessed by a gel filtration column assay. Follicular fluid and plasma leptin levels were similar (median 1135 pmol/l vs. 1409 pmol/l; p=0.81). Follicular fluid to plasma leptin ratio was independently associated with cumulative FSH dose (r=0.63; p=0.006) and insulin resistance index (r=-0.45; p=0.04). Specific leptin binding activity was higher in the plasma than in the follicular fluid [median 7.94% vs. 3.49%; p<0.001]. When multivariate analysis was used to predict FSH consumption, only follicular fluid leptin levels were significantly associated with cumulative FSH dose (r=0.46; p=0.04). We infer that at least in part by increased intrafollicular leptin levels, obesity directly affects ovarian function in PCOS, and may induce a relative resistance to gonadotropin stimulation. This intraovarian effect of leptin can be even more profound because of low leptin binding activity in the preovulatory follicle of obese patients. PMID- 11218149 TI - Time-dependent diagnostic performance of a rapid troponin T version 2 bedside test in patients with acute coronary syndromes. AB - In a prospective trial, the diagnostic performance of the second version of the troponin T rapid assay (Trop T; cutoff 0.2 microg/L) was compared with the quantitative cardiac-specific troponin T assay (cTnT ELISA; cutoff 0.1 microg/L) and other established cardiac markers such as CK, CK-MB activity, CK-MB mass and myoglobin. Additionally, a 30-day follow-up was performed to determine the suitability of the Trop T assay and the reference markers for short-term risk stratification. Two-hundred-and-eighty-six consecutive patients with chest pain and suspected acute myocardial infarction (AMI) were enrolled in two CCU departments. Serial blood specimens were taken at admission and at 3, 6, 12, 24, 48, 72 and 96 h after admission. According to the biochemical criterion CK-MB mass, the patients were classified as having AMI in 154 patients (54%), unstable angina (UAP) in 72 patients (27%) and no evidence for acute cardiac ischemia in 55 patients (19%). Analytical method comparison of Trop T with cTnT ELISA (cutoff 0.1 microg/L) showed a good agreement, Trop T yielded only 4% false-negative and 3% false-positive results. The diagnostic performance of Trop T for the detection of AMI was only slightly inferior compared to cTnT ELISA. Beyond 12 h after admission, Trop T and cTnT ELISA maintained a sensitivity close to 100%, whereas the sensitivity of the other cardiac markers decreased sharply. The diagnostic sensitivity of Trop T for the detection of minor myocardial damage in UAP patients was the same as for cTnT ELISA. Death within 30 days' follow-up occurred only in AMI patients with a positive Trop T test result within the first 6 h after admission. The admission Trop T and cTnT ELISA were the only significant biochemical predictors of major cardiac events. In conclusion, these data show that Trop T has similar diagnostic sensitivity as cTnT ELISA and is a useful tool to confirm acute or subacute myocardial infarction. Trop T is an excellent marker in detecting minor myocardial damage in UAP patients and is suitable for short term risk stratification. PMID- 11218148 TI - Traditional and alternative nutrition--levels of homocysteine and lipid parameters in adults. AB - Values of homocysteine and lipid parameters were measured in groups of adults consuming alternative nutrition (vegetarians/lactoovo/, vegans) and compared with a group consuming traditional diet (omnivores, general population). Frequency of hyperhomocysteinemia was 53% in the vegans group, 28% in vegetarians vs. 5% in omnivores. In conditions of lower methionine intake (reduced content in plant proteins), the remethylation pathway of homocysteine metabolism prevails and it is vitamin B12 and folate-dependent. The intake of vitamin B12 is equal to zero in vegans; vegetarians consume 124% of the RDA vs. 383% in omnivores. Serum vitamin levels are significantly lower in subjects consuming alternative nutrition with deficiency observed in 24% of vegetarians, 78% of vegans vs. 0% in omnivores. Serum folate levels are within the reference range in all groups. Mild hyperhomocysteinemia in the groups consuming alternative diet is a consequence of vitamin B12 deficiency. Vegetarians and vegans meet the RDA for energy and fat, and have a favourable proportion of saturated, mono- and polyunsaturated fatty acids on total energy intake; the ratio of linoleic/alpha-linolenic acid in their diet corresponds with the recommendations. They have low cholesterol consumption and higher vitamin E and C intake. Optimal fat intake of correct composition is reflected in lower values of atherosclerosis risk factors (cholesterol, LDL cholesterol, atherogenic index, saturated fatty acids, triacylglycerols), and significantly higher levels of protective substances (linoleic acid, alpha linolenic acid, HDL-cholesterol, vitamin E, vitamin E/cholesterol, vitamin C). Low lipid risk factors but higher findings of mild hyperhomocysteinemia in vegetarians mean a diminished protective effect of alternative nutrition in cardiovascular disease prevention. PMID- 11218150 TI - Validation of inductively coupled plasma atomic emission spectrometry technique (ICP-AES) for multi-element analysis of trace elements in human serum. AB - The use of inductively coupled plasma atomic emission spectrometry (ICP-AES) for the simultaneous determination of Al, B, Ba, Be, Cd, Co, Cr, Cu, Fe, Li, Mn, Ni, Pb, Se, Sr and Zn in human serum in a clinical laboratory was validated. Samples were digested and then analysed using yttrium as an internal standard and a serum matched calibration standard. The criteria used to assess the analytical performance of the ICP-AES were detection and quantification limits, linearity, sensitivity, recovery, interference from alkali and acid, trueness and precision. Detection limits were 0.002-0.003 micromol/L for Mn, Sr, Ba, and Cd; 0.014-0.07 micromol/L for Co, Zn, Fe, Be, Li, Pb, Cu, Ni, and Cr; and 0.2-0.9 micromol/L for B, Se, and Al. Trueness, as controlled by analysis of bovine serum certified reference material, was acceptable for Co, Cu, Se and Zn, while Fe was 5.1% and Mn 6.2% below the lowest limit of the certified material interval. We conclude that ICP-AES can be used for multi-element analysis of B, Ba, Cu, Fe, Li, Se, Sr and Zn in serum. Serum levels of Al, Be and Co were below the detection limits while serum levels of Cd, Cr, Ni and Pb were below the quantification limits of the ICP-AES. These trace metals cannot be analysed as routine by the ICP-AES. However, in cases of intoxication with elevated serum concentrations mean recovery of 100+/-10% was obtained at an addition of 2.22 micromol/L for Al, 0.11 micromol/L for Be, 0.03 micromol/L for Co, 0.39 micromol/L for Cr, 0.14 micromol/L for Ni, and 0.12 micromol/L for Pb. PMID- 11218152 TI - Comparison of iohexol and lactulose-mannitol tests as markers of disease activity in patients with inflammatory bowel disease. AB - Increased intestinal permeability has been proposed as one aetiological factor for inflammatory bowel diseases (IBD). We have previously found that intestinal permeability of a water-soluble contrast medium, iohexol, correlates with disease activity. The objective was to compare the iohexol test with the lactulose mannitol ratio, which is a more extensively studied permeability marker, in patients with active IBD. Urinary excretion of iohexol was compared to the lactulose-mannitol ratio in 22 patients with an exacerbation of IBD and in 10 healthy controls. Median intestinal absorption of iohexol was 0.64% (range 0.13 3.8%) in the 22 patients and 0.3% (range 0.15-0.54%) in the controls (p = 0.016), whereas the median lactulose-mannitol ratio was 0.037 (range 0.01-0.260) in patients and 0.03 (range 0.004-0.063) in controls (N.S.). Correlation between urinary excretion of iohexol and lactulose-mannitol ratio was positive (R = +0.41, p = 0.018). The urinary excretion of iohexol correlated positively with endoscopic disease activity (R = +0.74, p < 0.001) and the modified Harvey Bradshaw index (R = +0.44, p = 0.04). The lactulose-mannitol ratio correlated positively with endoscopic disease activity (R = +0.44, p = 0.05), but correlations with clinical index or c-reactive protein were poor. In conclusion, the iohexol test is a superior activity marker compared to the lactulose-mannitol ratio which probably reflects, instead, some pathogenic property of IBD. PMID- 11218151 TI - Random C-peptide in the classification of diabetes. AB - OBJECTIVE: To clarify whether random C-peptide is a valuable test in the classification of diabetes. RESEARCH DESIGN AND METHODS: All C-peptide measurements conducted in the diabetic population of Skaraborg (280,539 inhabitants and 3.2% diabetes) between 1995 and 1998 (3,115 samples) were considered, but only patients with well-defined diabetes type (1,449 samples from 1,093 patients) were analyzed for the correlation between diabetes type and C peptide concentration. Serum C-peptide was measured after fasting over night (fCP), after glucagon stimulation (gCP), and randomly (rCP) without considering previous meals at an ordinary visit to the diabetic clinic (rCP). Receiver Operating Characteristic (ROC) curves were constructed to illustrate the power of the different C-peptide protocols and to determine the optimal cut-off values. RESULTS: Although all three tests had high discriminative power, the ROC curves demonstrated that rCP was superior to fCP and gCP in discriminating type 1 from type 2 diabetes. The optimal cut-off value for rCP was 0.50 nmol/L, for fCP 0.42 nmol/L, and for gCP 0.60 nmol/L. CONCLUSIONS: rCP is more powerful than fCP and gCP in distinguishing type 1 from type 2 diabetes and can therefore be recommended as a classification tool, particularly in outpatients. PMID- 11218153 TI - A classification of circadian blood pressure profiles using a cumulative chi square technique. AB - Non-invasive ambulatory blood pressure monitoring has been used to assess circadian rhythms in blood pressure in a qualitative fashion. However, there are no established methods for assessing circadian changes in blood pressure in a quantitative fashion. In this study, we developed a quantitative method to evaluate the circadian rhythm based on profile analysis and a cumulative chi square technique. This method was used to analyse the circadian blood pressure variations in 100 normotensive volunteers and 127 hypertensive patients. Three blood pressure profiles were identified for the normotensive group, while four were identified for the hypertensive group. Furthermore, there was a relationship between the discriminate blood pressure profiles and the severity of hypertension. We conclude that profile analysis of 24-h ambulatory blood pressure monitoring may be used to stratify patients with regard to the risk of complications of hypertension. PMID- 11218154 TI - Biological variation and analytical imprecision of CA 125 in patients with ovarian cancer. AB - Despite the availability of serial data on CA 125 in ovarian cancer, the problem of interpreting a change over time is still unsolved. Changes in marker concentrations are due not only to patients improving or deteriorating but also to analytical imprecision and normal intra-individual biological variation. The aim of this study was to assess the analytical imprecision (CV(A)) and the intra- and inter-individual biological variation (CV(I) and CV(G), respectively) of CA 125 in a group of 26 patients with clinically stable ovarian cancer. Furthermore, the critical difference for a change between two consecutive CA 125 concentrations calculated as square root(2) x Z x (CV(A)2 + CV(I)2)(1/2) (Z =1.65 for unidirectional and 1.96 for bidirectional changes, p < or = 0.05) and the index of individuality calculated as ((CV(A)2+CV(I)2)/CV(G)2)(1/2) were estimated. After the exclusion of outliers, CV(A) and the average CV(I) and CV(G) were 12.1%, 24.0%, and 43.1%, respectively. The index of individuality was 0.62 and the critical difference calculated for unidirectional changes was 62.6%. CV(A) and CV(I) contribute considerably to the variation in serial results and should, therefore, be included in the criteria for serum tumor marker assessment during monitoring of patients with ovarian cancer. The cut-off value of CA 125 is of minor value in detecting unusual results for an individual subject, when previous measurements from an individual are available. These measurements should be preferred as reference for interpretation of new results. PMID- 11218155 TI - Short-term stimulation of vascular smooth muscle cells with platelet-derived growth factor (PDGF)-BB and angiotensin II induces. AB - Growth factors such as the platelet-derived growth factor (PDGF)-BB and angiotensin II (Ang II) have been shown to induce vascular smooth muscle cell (VSMC) proliferation after long stimulation periods. Little is known though, about the effects of PDGF-BB and Ang II on VSMC proliferation after short stimulation periods. The purpose of our study was to examine whether a short term (3-60 min) stimulation of VSMC with PDGF-BB or Ang II is sufficient to induce cell proliferation. Incubation of VSMC with Ang II (100 nM) or PDGF-BB (50 ng/ml) caused a significant increase in [3H]thymidine incorporation starting after a 3 min stimulation, while the cell counts required 32 and 8 h of stimulation, respectively. Mitogen-activated protein kinase activation reached a maximum at 5 10 min of PDGF-BB or Ang II stimulation. This study demonstrates that the growth promoting effects of PDGF-BB and Ang II are strongly dependent on the length of the stimulation period and that while prolonged stimulation periods (>8-32 h) result in VSMC proliferation, short ones (3-60 min) result only in [3H]thymidine incorporation without an increase in cell count, a fact of considerable pathophysiological significance, considering that the time kinetics of growth factors in the VSMC microenvironment have not as yet been clarified. PMID- 11218156 TI - Updating biological variation databases and selecting reasonably correct published values. PMID- 11218157 TI - The history of Crohn's disease. AB - Although it is likely that cases of what we know as granulomatous inflammatory bowel disease (Crohn's disease) may have been recorded as early as 1769, this illness is basically a disease of the 20th century. This historical review traces the development of our understanding of the disease and the evolution of its operative management. PMID- 11218159 TI - Crohn's disease of the foregut. AB - Historically, Crohn's disease of the esophagus, stomach, and duodenum has been reported only rarely. With more frequent use of upper endoscopy, however, upper gastrointestinal involvement has been found to be more common than previously suspected. The surgeon with an interest in Crohn's disease needs to be familiar with all areas that are potentially affected in this perplexing and sometimes devastating disease. This article examines the literature on foregut Crohn's and discusses the incidence, clinical manifestations, diagnosis, medical management, surgical indications, and operative techniques. PMID- 11218158 TI - Nutritional support for Crohn's disease. AB - This article reviews nutritional considerations that arise in the care of patients with Crohn's disease. The causes and presentation of malnutrition in these patients are discussed, and a rational method is presented for comprehensive nutritional assessment. The indications for nutritional intervention, either as supportive or primary therapy for Crohn's disease, are reviewed. PMID- 11218160 TI - Surgical pathology of Crohn's disease. AB - This article discusses the gross endoscopic and histologic features of Crohn's disease. Terms used to describe the pathologic features are defined, and possible mechanisms and implications of development are discussed. The gross endoscopic and histologic correlation and the roles of the pathologist and endoscopist in making the diagnosis of Crohn's disease are emphasized. PMID- 11218161 TI - Crohn's disease of the small bowel. AB - Crohn's disease of the small bowel frequently requires surgical intervention. While dealing with the disease complications that require intervention, treatment should be based on a long-term strategic plan that recognizes the likelihood of recurrent disease, repeat surgeries, and the possibility of a future ostomy. Resection forms the basis for surgical treatments, but strictureplasty, abscess drainage, intestinal and diversion bypasses also are used, selectively. PMID- 11218162 TI - Crohn's disease of the colon. AB - The surgical treatment of Crohn's disease of the colon is distinct from that used in treating ulcerative colitis. Crohn's disease often involves the small bowel and is not "cured" by colorectal resection. The popular ileo-anal pouch procedures used in the management of ulcerative colitis generally are not used for the treatment of Crohn's colitis, because of higher complication rates. Commonly performed operations include ileostomy, segmental colon resection, subtotal colectomy, and proctocolectomy. The general surgeon, therefore, is provided with many options when faced with complications of Crohn's colitis. This article examines the attributes of and results reported for each of these options. PMID- 11218164 TI - Intestinal stomas in Crohn's disease. AB - Stomal construction is as important as the establishment of hemostasis. Appropriate preoperative assessment and adherence to accepted construction techniques usually will avoid stomal complications. In patients who suffer adverse consequences, accurate assessment and appropriate management principles are essential to properly address the problem. PMID- 11218163 TI - Anorectal Crohn's disease. AB - Anorectal disease affects many patients with Crohn's disease. Clinical manifestations vary from asymptomatic skin tags to severe, debilitating perineal destruction and sepsis. Surgical management needs to be conservative and must focus on draining septic sites, preserving sphincter function, and palliating symptoms. Medical management has had some success in improving symptoms, but as yet, it has not been able to ameliorate most perianal complaints quickly and enduringly. Many new and exciting treatment modalities are being investigated with the hope that more effective approaches to these complex and difficult problems can be realized. PMID- 11218165 TI - Urologic complications of Crohn's disease. AB - Crohn's disease frequently can affect the genitourinary system, mainly in the form of urinary fistulae and urolithiasis. Diagnostic evaluation of fistulae associated with Crohn's disease has improved with the increasing use of computed tomography and MR imaging, along with other diagnostic modalities. Resective surgery is the main treatment in this group of patients. Kidney stones are common because of metabolic derangements and dehydration; however, these can be treated adequately with minimally invasive procedures, such as extracorporeal shock-wave lithotripsy, ureteroscopy, and percutaneous surgery. In addition, medical therapies can prevent recurrent stones. PMID- 11218166 TI - Laparoscopic surgery in Crohn's disease. AB - Laparoscopic surgeons attempting to treat Crohn's disease must have experience working with inflammatory bowel disease and advanced laparoscopic skills. Nonetheless, laparoscopy is dramatically changing all aspects of gastrointestinal surgery and inflammatory bowel disease, including Crohn's disease, is likely to benefit, as well. This article defines the role of laparoscopy in treating Crohn's disease and outlines surgical therapy. PMID- 11218167 TI - Psychosocial aspects of Crohn's disease. AB - In clinical practice, significant discrepancies occur between disease activity and severity, and the patient's symptom experience and behavior. Discrepancies cannot be explained by biologic or morphologic findings, and usually are considered to be related to psychosocial factors. Recent advances in the scientific understanding of the relationship between environmental stress and the neural, endocrine, and immune systems, combined with new methodologies in clinical research, provide a challenging opportunity for clinicians and researchers to establish a more comprehensive understanding of Crohn's disease. This article reviews the important relationship of psychosocial factors, pathogenesis, clinical expression, response to treatment, and outcome of Crohn's disease, and presents a comprehensive model of illness, disease, and ways to integrate psychosocial factors with diagnosis and patient care. PMID- 11218168 TI - Molecular genetics and Crohn's disease. AB - This article reviews basic molecular genetics and summarizes recent work in the genetics of Crohn's disease. Family studies are summarized, and candidate genes are described. The current state of knowledge and the implications of possible inheritance of Crohn's disease for patient care are discussed. PMID- 11218169 TI - Radiologic and endoscopic diagnosis of Crohn's disease. AB - This article reviews the radiologic and endoscopic diagnosis of Crohn's disease. Radiographic and endoscopic findings of Crohn's disease are discussed; a practical approach to the selection of radiologic modalities is presented; and the role of endoscopy in diagnosis and treatment is explained. PMID- 11218170 TI - Medical therapy for Crohn's disease: the state of the art. AB - Various medications are used to control the symptoms of Crohn's disease. This article reviews the traditional medical therapies of Crohn's disease, including aminosalicylates and corticosteroids, and the broad armamentarium of immune modulators and biologic agents that are becoming increasingly important in the management of Crohn's disease. PMID- 11218171 TI - Monitoring health reform: a report card approach. AB - During the past several years, budget cuts have forced hospitals in several countries to change the way they deliver care. Gilson (Gilson, L. (1998). DISCUSSION: In defence and pursuit of equity. Social Science & Medicine, 47(12), 1891-1896) has argued that, while health reforms are designed to improve efficiency, they have considerable potential to harm equity in the delivery of health care services. It is essential to monitor the impact of health reforms, not only to ensure the balance between equity and efficiency, but also to determine the effect of reforms on such things as access to care and the quality of care delivered. This paper proposes a framework for monitoring these and other indicators that may be affected by health care reform. Application of this framework is illustrated with data from Winnipeg, Manitoba, Canada. Despite the closure of almost 24% of the hospital beds in Winnipeg between 1992 and 1996, access to care and quality of care remained generally unchanged. Improvements in efficiency occurred without harming the equitable delivery of health care services. Given our increasing understanding of the weak links between health care and health, improving efficiency within the health care system may actually be a prerequisite for addressing equity issues in health. PMID- 11218172 TI - Competitive health policies and community health. AB - Since 1992 there have been fundamental changes in health care policy in Victoria, Australia, as the state government moves to competitive market models of service delivery and the measurement of service provision through output based funding. The introduction of competitive relationships to the public health system has had a major impact in the primary health care sector, particularly on community health centres. Most community health centres in Victoria have traditionally been semi-independent agencies controlled by community based committees of management. Such policies have had huge implications for the management and organisation of these agencies, as they have led to different patterns of service delivery and different models of management practice, often devaluing traditional philosophical perspectives of 'primary health care practice'. Although many agencies have embraced change as providing opportunities for growth and development and to have more influence in the provision of mainstream public health care, primary health care models of practice should be supported for their intrinsic and increasing value. PMID- 11218173 TI - Networks and tuberculosis: an undetected community outbreak involving public places. AB - After decades of decline in developed countries, there was a resurgence of tuberculosis in the mid-1980s accompanied by increased recognition that this infectious disease has long remained a major public health problem at the global level. New methods from molecular biology, in particular DNA 'fingerprinting' (of Mycobacterium tuberculosis), made it clear that current transmission and recent infection (in contrast to reactivation of earlier, latent infection) were much more significant than previously believed. Studies of tuberculosis outbreaks using these new tools pointed to complex networks through which infection was spreading and highlighted the need for new approaches to outbreak investigation and disease control. In the study reported here a new approach--combining methods from molecular biology, epidemiology and network analysis--was used to examine an outbreak of tuberculosis in Houston, Texas. Initial investigation using conventional strategies revealed few contacts among 37 patients with identical (six-band) DNA (IS6110-based) fingerprints but subsequent research uncovered over 40 places (including many gay bars) to which patients in this outbreak could be linked. Network methods were used to reconstruct an outbreak network and to quantify the relative importance (here, 'betweenness' centrality) of different actors (persons and places) playing a role in the outbreak. The multidisciplinary work provides the basis for a new approach to outbreak investigation and disease control. PMID- 11218174 TI - Primary care as intersecting social worlds. AB - An enhanced role for primary health care (PHC) is currently a matter of political priority in the UK. This higher profile is drawing attention to a range of unresolved challenges and issues, relating to both the structure and content of provision, which currently permeate the system. Running in parallel with this is a recognition that: to date, PHC has been under-researched; that, as a result, our understanding of it is frequently poor; and that, as a consequence, fresh perspectives are needed in order to effectively research this uncertain, evolving and increasingly important healthcare sector. In this paper we argue that social worlds theory (SWT) provides, albeit in a suitably modified form, an ideal conceptual framework for the analysis of contemporary primary care. SWT is an approach which assumes complexity and constant evolution, and its core concepts are directed towards unravelling the consequences of encounters between different interest groups--something which is of particular utility at this time given the increasing attention to user participation, and an ongoing questioning of established patterns of professional authority. It is an approach which has rarely been employed empirically, even beyond medicine. In order to illustrate the wide relevance of the approach, we discuss how it can facilitate research at all levels of PHC: i.e., in relation to aspects of medical practice (the case of medically unexplained symptoms); shifts in service organisation (changing professional roles and the introduction of policy reforms); and issues which straddle both organisation and content (the increasing use of complementary medicine in primary care). In each case the approach is able to embrace the complexity of situations characterised by the intersection of professional and lay social worlds and is able to provide the conceptual tools through which resultant processes can be tracked and investigated. PMID- 11218175 TI - The social construction of male 'homosexuality' in India: implications for HIV transmission and prevention. AB - Over the past 20 years, there has been a growing recognition of the relativity of sexual norms and of the difficulties of exporting Western conceptions of sexuality to different socio-cultural settings. This view has been most clearly articulated in studies of men who have sex with men (MSM) which suggest that the ways in which male-male sexual activity is shaped and constituted vary significantly from place to place. Despite this, 'homosexuality' continues to be treated as an unproblematic category in HIV/AIDS discourse, epidemiological studies of and HIV prevention strategies for MSM in widely different contexts being based on the North American/West European example of gay men. This paper, which draws upon ethnographic research in Madras, highlights important differences between India and the West, not only in the sexual identities and circuits of MSM, but in their sexual partnerships and practices. These differences, it is argued, are not only significant to the epidemiology of HIV transmission, but have important implications for the development and implementation of HIV prevention strategies. PMID- 11218176 TI - Implementing AIDS policy in post-apartheid South Africa. AB - In common with the rest of the Southern African sub-continent. South Africa is currently experiencing a serious HIV epidemic. When it came into power in 1994, the new, Mandela-led government immediately mobilised funds and adopted a far reaching AIDS Plan for the country. However, the implementation of AIDS policy in the first four years after 1994 has been characterised by a lack of progress and a breakdown of trust and co-operation, both within government and between government and NGOs. This paper outlines the political context which shaped the development of the AIDS Policy, then examines the difficulties of implementing a comprehensive response to AIDS in a country undergoing restructuring at every level. It questions the notion of "inadequate political will" as an explanation for lack of progress. Involvement by politicians has, in fact, been experienced as a double-edged sword in South Africa, with inappropriate, "quick-fix" actions creating conflict and hampering a more longer-term, effective response. The paper also highlights the importance of groupings outside of government in promoting effective policy actions, and the types of leadership required to mobilise a broad range of actors around a common vision. It concludes by emphasising the need to develop approaches to policy implementation rooted in the possibilities and constraints of the local situation, rather than relying on universal blue prints developed out of context. PMID- 11218177 TI - Relationship dynamics and teenage pregnancy in South Africa. AB - Teenage pregnancy is extremely common in South Africa. Whilst its 'problematic' nature is a subject of debate, it reflects a pattern of sexual activity which puts teenagers at risk of HIV. Currently one in five pregnant teenagers is infected with the virus. This creates a new imperative to understand teenage pregnancy and the pattern of high risk sexual activity of which it is one consequence. This was an exploratory study undertaken to investigate factors associated with teenage pregnancy amongst sexually active adolescents in an urban and peri-urban context. The study used a matched case control design, with 191 cases and 353 school or neighbourhood, age-matched controls. Subjects were under 19 years and recruited from township areas of Cape Town. A structured questionnaire was used to obtain information on socio-economic factors, contraceptive knowledge and use, and sexual behaviour. Conditional logistic regression was used to analyse the relationship between teenage pregnancy and the factors investigated. The results presented focus on relationship dynamics and their association with the risk of pregnancy. Both groups of teenagers had been dating for a mean of two and a half years and about half were still with their first sexual partner. The partners of the pregnant teenagers were significantly older, less likely to be in school and less likely to have other girlfriends. The pregnant teenagers were significantly more likely to have experienced forced sexual initiation and were beaten more often. They were much less likely to have confronted their boyfriend when they discovered he had other girlfriends. Multiple modelling shows that both forced sexual initiation and unwillingness to confront an unfaithful partner are strongly associated with pregnancy and also related to each other. We argue that the associations are mediated through unequal power relations within the relationship which are reinforced by violence. We further discuss indicators of greater intimacy within relationships of the pregnant teenagers which may suggest that more of the pregnancies were wanted than was suggested. Both of these conclusions pose critical challenges for health promoters. PMID- 11218178 TI - China's one-child policy: the economic choices and consequences faced by pregnant women. AB - This paper addresses the important issue of the effect of China's one-child policy on prenatal and obstetric care utilization. The paper provides the first detailed empirical approach to this question, exploiting a unique high quality household survey. China officially codified a set of rules and regulations in 1979 governing the approved size of Chinese families, commonly known as the one child policy. The policy imposed economic and social costs on families failing to adhere to the family size limits. In particular, the policy raised the price of obstetric medical services for unapproved pregnancies in comparison to approved pregnancies and imposed fines on families with unapproved births. Using data from an eight-province longitudinal household survey (The China Health and Nutrition Survey), we investigate whether or not the one-child policy's financial penalties were associated with the avoidance of obstetric care by pregnant Chinese women with unapproved pregnancies. The one-child policy variables of particular interest were a dichotomous measure of the approval status of the pregnancy, a continuous measure of the fine imposed upon families with unapproved births, and a continuous measure of the prices of prenatal care and delivery services net of any subsidy available for approved births. The results partially confirm the hypotheses that the one-child policy's economic and social costs caused women to forego seeking modern obstetric care services. The fine was found to be a significant deterrent to the utilization of prenatal care. Additionally, the unapproved-status of a pregnancy was strongly negatively associated with "the use of obstetric care. However, higher prices were not consistently found to be a significant deterrent to the use of obstetric care. PMID- 11218179 TI - Dimensions of social inequality in the health of women in England: occupational, material and behavioural pathways. AB - This paper examines the role of behavioural and psychosocial risk and protective factors in explaining social inequalities in the general self-assessed health of women. Using path analysis, data from the Health Survey for England (1993) are used to demonstrate how different dimensions of social position (working conditions, general social advantage and material deprivation) have distinct pathways to ill-health. Smoking, diet, alcohol consumption, exercise, social support and job strain were all related to poorer health, but not always in the predicted direction. The effects of social position on health were not fully mediated through these risk and protective factors. Each dimension of social position had unique pathways to ill-health via other unidentified mechanisms. Furthermore, the salience of the three dimensions of social position differed according to the level of labour market attachment. Different path models are required to fit the data for women at home or in full-time or part-time work. PMID- 11218180 TI - "It's some kind of women's empowerment": the ambiguity of the female condom as a marker of female empowerment. AB - The female condom is the latest in a series of sexual and reproductive technologies to be imported into the third world, following the contraceptive pill, the Depo-Provera injection, the latex male condom, and others. It is an example of "traveling technology", which accrues different meanings and connotations in the different settings into which it is introduced in its journey through the circuits of international technological diffusion, from the headquarters of international NGOs and bilateral aid programs, through the bureaucracies of national ministries of health to the communities in urban and rural settings where the condoms are distributed. The female condom almost always carries connotations of women's empowerment, and the possibility of greater sexual autonomy for women. This association is a result of the female condom being the first new "post-Cairo" technology, the diffusion of which was spurred by the consensus reached at the 1994 International Conference on Population and Development in Cairo, at which the need to promote women's empowerment was moved to the center of international family planning and population movements. However, I demonstrate that "empowerment" is an ambiguous term, interpreted in different ways in different contexts. I illustrate this through interviews conducted in 1998 and 1999 with stakeholders in the female condom in Cape Town, Nairobi, and in rural western Kenya. These stakeholders range from directors of US-based development programs to heads of national AIDS-prevention efforts to community based distributors and primary health care nurses at the village level. I argue that three different notions of empowerment are being articulated with respect to the female condom--two which correspond to Maxine Molyneux's typology of strategic and practical gender interests, and a third in which women's empowerment is conceived of as something which diminished the power of men. I argue further that the disjunctures between these three different notions of what "empowerment" means will pose a challenge for people at all levels which are seeking to make the female condom more widely accessible to women at risk of HIV/AIDS. PMID- 11218181 TI - African Americans' views on research and the Tuskegee Syphilis Study. AB - The participation of African Americans in clinical and public health research is essential. However, for a multitude of reasons, participation is low in many research studies. This article reviews the literature that substantiates barriers to participation and the legacy of past abuses of human subjects through research. The article then reports the results of seven focus groups with 60 African Americans in Los Angeles, Chicago, Washington, DC, and Atlanta during the winter of 1997. In order to improve recruitment and retention in research, the focus group study examined knowledge of and attitudes toward medical research, knowledge of the Tuskegee Syphilis Study, and reactions to the Home Box Office production, Miss Evers' Boys, a fictionalized version of the Tuskegee Study, that premiered in February, 1997. The study found that accurate knowledge about research was limited; lack of understanding and trust of informed consent procedures was problematic; and distrust of researchers posed a substantial barrier to recruitment. Additionally, the study found that, in general, participants believed that research was important, but they clearly distinguished between types of research they would be willing to consider participating in and their motivations for doing so. PMID- 11218182 TI - Low incidence of hereditary nonpolyposis colorectal cancer syndrome in a selected area of the Lombardy Cancer Registry. AB - AIMS AND BACKGROUND: Epidemiological investigations on the frequency of hereditary nonpolyposis colorectal cancer (HNPCC) syndrome are few and have shown a variable worldwide incidence ranging from 1% to 7% of all colorectal cancers (CRCs). In Italy, relevant differences have been observed: 2.8-3% of all CRCs in northern regions and less than 1% in southern regions. The aim of the present study was to investigate the HNPCC incidence in a selected area of northern Italy belonging to the Lombardy Cancer Registry. METHODS AND STUDY DESIGN: We analyzed 197 consecutive patients with newly diagnosed CRCs, histologically verified, and resident in two areas of the Lombardy Cancer Registry. For each case, genetic counseling with at least three generations pedigree reconstruction, HNPCC classification according to Amsterdam criteria, molecular analysis for microsatellite instability and immunohistochemistry for hMLH1 and hMSH2 were performed. RESULTS: A very low frequency (0.5%) of HNPCC fulfilling the Amsterdam criteria was found in comparison to the other Italian areas. Such an incidence seems to be due to actual population differences and reflects a genetic heterogeneity. CONCLUSIONS: The data underline the importance of a precise knowledge of actual HNPCC incidence in different populations in order to optimize effectiveness and efficiency of screening programs for the disease. PMID- 11218183 TI - Histopathologic interobserver agreement on the diagnosis of melanocytic skin lesions with equivocal dermoscopic features: a pilot study. AB - AIMS AND BACKGROUND: Dermoscopy (dermatoscopy, skin surface microscopy, epiluminescence microscopy) has been increasingly employed in recent years for the preoperative detection of cutaneous melanoma, and dermatoscopic features of pigmented skin lesions have been previously defined using histopathology (HP) as the "key to the code". The aim of the present study was to evaluate the interobserver agreement on the HP diagnosis in a series of epiluminescence microscopy equivocal melanocytic skin lesions. STUDY DESIGN: Ten melanocytic skin lesions were selected on the basis of diagnostic disagreement of at least 2 out of 9 epiluminescence microscopy observers. The histologic specimens from the 10 lesions were examined by 9 HP observers. The agreement of the HP diagnoses was calculated by means of Fleiss' k statistics. RESULTS: The overall HP agreement was less than excellent (k = 0.5). When considering the prevailing epiluminescence microscopic and HP diagnoses, 2 cases were shown to be epiluminescence microscopy false-negative melanomas. Virtually no agreement was found among epiluminescence microscopy observers in 4 cases (40%) or among HP observers in 3 cases (30%). However, only one pigmented skin lesion remained unclassifiable on epiluminescence microscopy as well as HP. CONCLUSIONS: When at least 2 epiluminescence microscopy experts disagree in the evaluation of a given melanocytic skin lesion, even HP consultations may give equivocal results. The need to establish more reliable epiluminescence microscopic and HP criteria by performing an improved and meticulous clinicopathologic correlation, e.g. by using telecommunication via Internet, is emphasized. PMID- 11218184 TI - Ovarian germ cell cancer: clinicopathologic analysis and outcome of 31 cases. AB - AIMS: The aim of the study was to evaluate some clinicopathologic characteristics and the outcome of patients with ovarian germ cell cancer (OGCC) treated with cisplatin-based chemotherapy. METHODS: It was a clinical retrospective study. The clinical charts of 31 patients with OGCC assisted at the Department of Obstetrics and Gynecology of the State University of Campinas, Brazil, from January 1986 to June 1997 were reviewed. RESULTS: Ten patients had dysgerminoma and 21 patients nondysgerminomatous tumors. Women with dysgerminoma and nondysgerminomatous tumors did not present differences regarding surgical staging, age, ascites or residual tumor after the initial surgery. Frozen section, performed in 16 patients, showed some discrepancy with paraffin histology diagnosis in 8 patients. Platinum-based chemotherapy was used in 5/10 patients with dysgerminoma and in 17/21 patients with nondysgerminomatous tumors, with a 5-year survival of 100% for the dysgerminoma and 53% for the nondysgerminomatous group. CONCLUSIONS: Women with dysgerminoma and nondysgerminomatous tumors did not present differences regarding clinicopathologic characteristics. The prognosis for patients with dysgerminoma was better than for those with nondysgerminomatous tumors. Frozen section had a high error rate in diagnosing OGCC intraoperatively. PMID- 11218185 TI - Detection of false-negative Pap smears using the PAPNET system. AB - AIMS AND BACKGROUND: False-negative cytological diagnoses represent the critical point of a screening program for early detection of cervical cancer. Computer assisted reading using neural network technology has been suggested as a possible approach to manage the problem. The study assessed the performance and the cost outcome ratio of computer-assisted versus conventional manual Pap smear reading. METHODS: One thousand routine smears, seeded with 81 false-negative smears, were independently interpreted by two readers by conventional and PAPNET-assisted reading. Results of both readings were compared in terms of: a)sensitivity for false-negative smears, b)specificity, and c) cost-outcome (cost per CIN2+ lesion detected). RESULTS: PAPNET-assisted reading showed a small increase in sensitivity only for one reader. Including the cost of PAPNET, the cost per detected lesion would be $7,543 and the cost per additional detected lesion would be $25,748. CONCLUSIONS: The present study provides further evidence that PAPNET assisted screening may allow the detection of a few extra cases of CIN2+ lesions with respect to conventional reading, though at a very high cost. PMID- 11218186 TI - Cellular and clinical pharmacokinetic/pharmacodynamic basis for lack of efficacy of 21-day continuous topotecan in patients with untreated advanced adenocarcinoma of the pancreas. AB - BACKGROUND: In a phase II study, topotecan was evaluated for response and toxicity in patients with advanced pancreatic carcinoma at the schedule of 0.7 mg/m2/day q 21 days q 28 days. METHODS: Responses were assessed after at least 2 courses using WHO criteria, and toxicity was evaluated after each course according to the CTC-NCI standards. Between December 1995 and September 1997, 15 assessable patients (median age, 55 years; range, 36-74; median ECOG performance, 1; range, 0-3) were included in the study. All had biopsy-proven and measurable disease, a life-expectancy of at least 3 months, and normal bone marrow, liver, and renal function. None of the patients had undergone prior cytotoxic or radiation therapy, and 10 were initially treated by surgery. Twenty-five cycles were assessable for toxicity. Plasma was collected from 7 patients who had received a total of 10 cycles and was, after extraction with methanol at -20 degrees C, analyzed for total topotecan by an HPLC method. The thus determined steady-state concentrations were assessed for their capacity to affect growth and DNA integrity in the BxPC-3 human pancreatic carcinoma cell line after 21 days of continuous exposure. For these purposes, we used a sulforhodamine B staining assay, and agarose gel electrophoresis, respectively. RESULTS: Grades 3-4 leukopenia, thrombocytopenia, granulocytopenia, and anemia occurred in 8, 6, 8 and 8 cycles, respectively. Other mild to moderate side effects (grades 1-2) included malaise, nausea and vomiting, anorexia, and alopecia. No objective tumor response was documented. HPLC analysis of patients' plasma showed the attainment of constant steady-state levels of 1.0+/-0.1 ng/mL during the entire infusion period. At such a concentration, topotecan did not significantly affect growth or DNA integrity in the BxPC-3 cells. Fifty percent cell growth inhibition and appreciable oligonucleosomal DNA fragmentation were only evident with 21 days topotecan > or = 50 ng/mL. CONCLUSIONS: Our data suggest that the lack of clinical activity of 0.7 mg/m2 daily topotecan for 21 days q 28 days in patients with advanced pancreatic carcinoma might be partially attributed to the achievement of non-tumoricidal plasma drug concentrations. PMID- 11218187 TI - The value of oxaliplatin in combination with continuous infusion +/- bolus 5 fluorouracil and levo-folinic acid in metastatic colorectal cancer progressing after 5FU-based chemotherapy: a GISCAD (Italian Group for the Study of Digestive Tract) cancer phase II trial. AB - AIMS AND BACKGROUND: The phase II trial was designed to evaluate the activity of combined oxaliplatin (L-OHP), continuous infusion (CI) +/- bolus 5-fluorouracil (5FU) and levo-folinic acid (I-FA) in patients with metastatic colorectal cancer progressing after one or more lines of 5FU-based chemotherapy. PATIENTS AND METHODS: We designed two contemporary studies: in the former we enrolled patients previously treated with 1 line of chemotherapy, and in the latter, patients previously treated with 2, 3 and 4 lines. Seventy-six consecutive patients were enrolled: 45 received L-OHP (85 mg/m2 i.v. 2 h on day 1) + I-FA (100 mg/m2 i.v. 2 h on days 1 and 2) + 5FU i.v. bolus (400 mg/m2 days 1 and 2) + 5FU (600 mg/m2 CI 22 h days 1 and 2 (FOLFOX 4); 31 received L-OHP (100 mg/m2 i.v. 2 h on day 1) + I FA (250 mg/m2 i.v. 2 h on days 1 and 2), followed by 5FU (1500 mg/m2 Cl 24 h days 1 and 2 (FOLFOX 2). The treatment was recycled every 2 weeks and continued until progression and/or unacceptable toxicity or patient preference. The primary end point was activity (tumor growth control [TGC]: partial response [PR] + stable disease [SD]); the secondary end points were time to progression (TTP), overall survival (OS) and toxicity. RESULTS: Forty-five patients in 2nd line (22 FOLFOX 4, 23 FOLFOX 2), 23 (17 FOLFOX 4, 6 FOLFOX 2) in 3rd, 4 in 4th and 1 in 5th line were assessable; 3 were lost to follow-up. In 15 patients (11 FOLFOX 4, 4 FOLFOX 2), disease involved the liver only. A total of 533 courses were administered with a range of 1-14 in FOLFOX4 and 1-12 in FOLFOX2; dose intensity was 92.85%, and the total dose of the administered L-OHP was 98.29%. As a 2nd line treatment, FOLFOX 4 achieved TGC in 72.8% of the patients (PR, 18.2%; SD, 54.6%), with a median TTP of 6 months and a median OS of 7 months, whereas in the FOLFOX 2 group these figures were 78.3% (PR 21.8%, SD 56.5%), and 5 and 9 months. As a 3rd line treatment, FOLFOX 4 produced TGC in 41.1% of patients (PR 23.5%, SD 17.6%), with a median TTP of 5 months and median OS of 7+ months, whereas FOLFOX 2 obtained respective values of 50% (PR 16.7%, SD 33.3%), 7 and 9 months. As a 4th line of treatment, TGC was achieved in 2 patients (1 PR, 1 SD); the patient in 5th line therapy obtained a SD. With "de Gramont" as the first-line regimen, patients assessable were 24 in FOLFOX 4 and 18 in FOLFOX 2. In the former population, TGC was 70.8% (PR 37.5%, SD 33.3%), with a TTP of 6 months and OS of 10 months, whereas with FOLFOX2 these values were 61.1% (PR 5.6%, SD 55.5), 5 and 7 months. In patients with liver involvement only, FOLFOX 4 obtained TGC in 63.6% of cases (with a TTP of 7 months and OS of 6+ months), FOLFOX 2 in 100% (with a TTP of 9.5 months and OS of 13.5+ months). Both schedules exhibited an acceptable toxicity: neurologic, hematologic and hepatic grade 3 side effects occurred in a limited number of patients, with a higher frequency in the FOLFOX 2 group. CONCLUSIONS: Treatment with L-OHP, CI +/- bolus 5FU and I-FA was well tolerated. The activity in terms of TGC was interesting and comparable with results reported in the literature for the standard treatment for 2nd line, i.e. irinotecan alone. Treatment was effective in 2nd line and in patients previously treated with more than two chemotherapy lines; in particular, treatment was active in patients with hepatic disease only. Although the two schedules seemed to achieve the same benefit with the same tolerance, we could not define from the study the better regime. PMID- 11218188 TI - Prognostic effects of lymph node micrometastases in patients undergoing curative gastrectomy for cancer. AB - AIMS & BACKGROUND: It is not known whether the presence of micrometastases in the regional lymph nodes has an impact on the oncologic outcome of patients undergoing a curative (R0) gastrectomy for cancer. The aim of the study was to assess the effects of the presence of micrometastases on survival. METHODS: We reviewed 29 patients operated on for curative (R0) gastrectomy, with a final diagnosis of pN0, 16 or more lymph nodes in the specimen, and a follow-up of at least 4 years. The original hemotoxylin and eosin slides were reviewed, and a new section was cut from the lymph nodes and immunostained with a pool of antibodies against different types of cytokeratins. Micrometastases were detected in 5 patients (27.5% of the series) and 11 lymph nodes (1.51% of all removed lymph nodes). RESULTS: Mortality due to cancer progression occurred in 3 patients from the pN0 group (14.2%) and 1 patient from the pN1 group (12.5%). CONCLUSIONS: There was no suggestion from the data that the presence of micrometastases carries an ominous prognosis in terms of survival. PMID- 11218189 TI - Clinical management of a case of recurrent apocrine gland carcinoma of the scalp: efficacy of a chemotherapy schedule with methotrexate and bleomycin. AB - Apocrine carcinoma of the skin is a rare tumor. Wide surgical excision with complete removal of the neoplasm is the standard therapy and this appears to offer the best chance of cure. Radiotherapy may be used in case of local relapse or regional lymph node involvement. Systemic chemotherapy has not proved to be effective in the treatment of this tumor. We report on a 46-year-old woman with a recurrent apocrine carcinoma of the scalp that had previously been treated with surgery, radiotherapy and chemotherapy (Al-Saraff schedule). The patient was responsive to a second-line systemic chemotherapy regimen consisting of a weekly combination of methotrexate and bleomycin, and achieved long-term progression free survival. PMID- 11218190 TI - Intra-arterial liver chemotherapy and hormone therapy in malignant insulinoma: case report and review of the literature. AB - BACKGROUND: Malignant insulinoma is a rare tumor. Metastatic disease confined to the liver can be treated with various locoregional treatments. CASE REPORT: We report a case of a young woman who developed liver metastases twelve years following resection of a pancreatic insulinoma positive to anti-insulin antibodies. With five cycles of intra-arterial locoregional chemotherapy (fluorouracil and epirubicin) to the liver and monthly hormone therapy (octreotide) the patient obtained a clinical complete response. After twelve months she is still disease free. CONCLUSION: Locoregional therapy for insulinoma metastatic to the liver might represent the treatment of choice; hepatic intra arterial chemotherapy is an interesting therapeutic approach which deserves attention. The role of somatostatin analogs is limited to symptom control. PMID- 11218191 TI - Testicular plasmacytoma in a patient with the acquired immunodeficiency syndrome. AB - Clinical, laboratory, and pathologic findings from a case of primary extramedullary plasmacytoma of the testis and sinuses in a patient with acquired immunodeficiency syndrome (AIDS) are presented. To our knowledge this is the first case in the English literature of a primary testicular plasmacytoma in an HIV-infected patient. The findings in this report and those of others confirm the difference in the pattern of plasma cell tumor (PCT) presentation in patients infected with AIDS from those in non-infected individuals, suggesting that these tumors should be considered in the differential diagnosis of AIDS-associated malignancies. PMID- 11218192 TI - Two episodes of ifosfamide-related neurotoxicity in the same patient following different schedules and doses of the drug. A case report. AB - We report the first case of recurrent ifosfamide-related neurotoxicity in the same patient following two distinct administrations of the drug at different doses and schedules and with a long interval between the two episodes. Remarkably, the first event was characterized by confusion and hallucinations, while the second, 29 months later, was characterized by partial and generalized seizures. Between the two episodes the patient had received high-dose cyclophosphamide, an oxazophoshorine agent closely related to ifosfamide, without any neurological side effects. We briefly discuss the diagnosis and management of ifosfamide-related encephalopathy. PMID- 11218193 TI - A young female patient with an androgen-secreting tumor: a rare malignant disease. AB - A 23-year-old female patient presented with hirsutism and fatigue nine months after delivery. Endocrine assessment showed high testesterone, DHEA-S and androstenedione levels. Abdominal computed tomography and ultrasonography revealed the presence of a large tumor in the right renal region. Right adrenalectomy was performed resulting in a diagnosis of a functional adrenal tumor. Pathological examination showed a steroidogenically active tumor. Adjuvant chemotheraphy was administered postoperatively. At three months following surgery all endocrinological tests normalized, but liver metastases were detected by abdominal CT. Eight months after the operation the patient died of hepatic and renal failure. Androgen-secreting adrenal tumors are seen very rarely, yet the prognosis is poor due to their agressive nature. PMID- 11218194 TI - Intrathoracic desmoid tumor of the posterior mediastinum with transdiaphragmatic extension. Report of a case. AB - We report on a de novo desmoid tumor of the posterior mediastinum with transdiaphragmatic extension in a 40-year-old man. The tumor was inoperable because of its location and the invasion of adjacent structures. Although extremely rare, desmoid tumors of the posterior mediastinum should be considered in the differential diagnosis of posterior mediastinal masses. PMID- 11218195 TI - Primary non-Hodgkin's lymphoma of the liver (case report). AB - Primary non-Hodgkin's lymphoma of the liver is very uncommon, and fewer than 100 cases have been reported in the literature. Most reports describe either solitary or multiple mass lesions in the liver. A diffuse lesion without nodule formation is a relatively rare form of the disease. The histologic feature of the disease is a predominantly large cell lymphoma of B-cell lineage. We report a case of primary B-cell non-Hodgkin's lymphoma which had diffusely infiltrated the liver without nodule formation. PMID- 11218196 TI - The role of outbreaks in developing food safety policy: population based surveillance of salmonella outbreaks in Wales 1986-98. AB - In developing public policy on food safety, systematic identification and thorough investigation of all general outbreaks is necessary in order to avoid bias towards highly publicised outbreaks. In Wales, from 1986 to 1998, 87 general foodborne outbreaks of salmonellosis were identified. Most outbreaks occurred at functions or were associated with small catering outlets such as bakeries and sandwich bars. In 50 outbreaks, a vehicle of infection was confirmed microbiologically and/or epidemiologically. The most common food vehicles were those containing shell eggs. Salmonella enteritidis outbreaks were significantly more likely than outbreaks of other serotypes to be associated with vehicles containing shell eggs, suggesting that eggs were also the source of infection in many outbreaks. The routine use of analytical epidemiological studies to identify vehicles in outbreaks is recommended. PMID- 11218197 TI - Emerging antibiotic resistance in Salmonella typhimurium in Norway. AB - The antimicrobial resistance of 809 Salmonella Typhimurium isolates collected from humans in Norway between 1975 and 1998 was studied. The material was subdivided into domestic and foreign isolates according to whether the patient had recently travelled abroad or not. In imported isolates the largest increase in resistance was in 1996 when 35% of the isolates were multi-resistant. The first multi-resistant isolate acquired in Norway appeared in 1994, but already in 1998 23% of the isolates domestically acquired were multi-resistant, and a majority were S. Typhimurium DT104. We found no ciprofloxacin resistance in domestically acquired isolates. Amplified fragment length polymorphism analysis was performed on selected multi-resistant isolates. The method discriminated well between different multi-resistant isolates, but not between DT104 isolates. Resistant and multi-resistant S. Typhimurium were until 1998 essentially recovered from patients who had travelled abroad, but multi-resistant isolates, mainly DT104, are now also being transmitted within the country. PMID- 11218198 TI - Usefulness of genetic typing methods to trace epidemiologically Salmonella serotype Ohio. AB - Different genetic typing procedures were applied in an epidemiological study of Salmonella serotype Ohio. Isolates that generated identical DNA fingerprints (HinclI ribotypes, ERIC and RAPD profiles) were clustered into the same lineage, and the addition of data from plasmid, integron and resistance profiles was used to differentiate types. Results led to the determination of the endemic and the emergent epidemic types at specific times, and to ascertain the clinical and epidemiological impact of each type. In the series analysed (47 clinical isolates and 3 non-clinical isolates) 11 lineages and 32 types were found. Two lineages were considered prevalent and endemic, and during an epidemiological alert (Spain, 1998) a re-emergence and spread of organisms mainly from the most frequent lineage had occurred. The combination of H-ribotype with ERIC profile, as primary markers, and resistance profile with plasmid profile, as secondary markers, was shown to be the most useful tool to trace epidemiologically Ohio. PMID- 11218199 TI - Initially unrecognized distribution of a commercially cooked meat product contaminated over several months with Salmonella serotype Infantis. AB - An outbreak of salmonellosis occurred among 63 wedding participants. The outbreak was investigated through cohort, laboratory, and environmental studies. Consumption of rice-dressing made from a commercially cooked, meat-based, rice dressing mix was strongly associated with illness. Nineteen patient isolates, six company/grocery store isolates cultured from the rice-dressing mix, and one environmental isolate from a pump in the production line were of an identical outbreak strain of Salmonella Infantis characterized by pulsed-field gel electrophoresis. In the production line, cooked rice-dressing mix tested negative for S. Infantis before and positive after contact with the contaminated pump. The dressing-mix had an estimated 200 colony-forming units of salmonella per gram of product, and > 180,000 pounds were distributed in 9 states for > or = 2 months before contamination was recognized. Food manufacturers should be required to use systematic, hazard analysis critical control point risk management practices for all processed meat products, validated by periodic microbiologic monitoring of the end product. PMID- 11218200 TI - A community waterborne outbreak of gastro-enteritis attributed to Shigella sonnei. AB - An outbreak of gastro-enteritis occurred in a community of 2213 persons located near the city of Ioannina, in North-western Greece. Two hundreds and eighty-eight inhabitants of the village of Eleoussa, suffered from gastro-enteritis between 11 and 22 October. The peak of the epidemic occurred during the first 3 days (11-13 October). The highest risk of developing gastro-enteritis was observed in the age group 0-14 years (41.4%) and decreased significantly with age (P < 0.01). Patients over 65 years were more frequently hospitalized than those in other age groups (P < 0.05). Shigella sonnei was isolated from both, water samples and faeces of patients. Control measures were implemented on the second day of the outbreak. Environmental conditions suggest that contaminationof the water system occurred by groundwater. PMID- 11218201 TI - Health burden in the Netherlands due to infection with thermophilic Campylobacter spp. AB - Infection with thermophilic Campylobacter spp. usually leads to an episode of acute gastroenteritis. Occasionally, more severe diseases may be induced, notably Guillain Barre syndrome and reactive arthritis. For some, the disease may be fatal. We have integrated available data in one public health measure, the Disability Adjusted Life Year (DALY). DALYs are the sum of Years of Life Lost by premature mortality and Years Lived with Disability, weighted with a factor between 0 and 1 for the severity of illness. The mean health burden of campylobacter-associated illness in the Dutch population in the period 1990-5 is estimated as 1400 (90% CI 900-2000) DALY per year. The main determinants of health burden are acute gastroenteritis (440 DALY), gastroenteritis related mortality (310 DALY) and residual symptoms of Guillain-Barre syndrome (340 DALY). Sensitivity analysis demonstrated that alternative model assumptions produced results in the above-mentioned range. PMID- 11218202 TI - An epidemiological study of Plesiomonas shigelloides diarrhoea among Japanese travellers. AB - Plesiomonas shigelloides is often regarded as a non-pathogenic bacterial species that is occasionally isolated from patients with diarrhoea. However, a review of travellers returning to Japan with diarrhoeal illness through Kansai Airport revealed that the incidence of P. shigelloides from microbiologically confirmed cases increased from 23.2% in 1987 to 77.8% in 1999. We carried out a descriptive epidemiological study to identify patterns associated with diarrhoea due to this organism. Selected P. shigelloides isolates from this patient group were compared by pulsed-field gel electrophoresis of SpeI total chromosomal DNA digests to determine their genetic heterogeneity. Over the study period (whole of 1996 and first 2 months of 1999), 1149 of 1659 (69.3%) patients with microbiologically confirmed gastroenteritis yielded P. shigelloides. Infection was characterized by watery diarrhoea five times per day that persisted for 3 days. No statistically significant association was found between factors such as age, gender, destination, length of trip, but multivariable logistic regression analysis revealed an association between additional symptoms (vomiting, fever, abdominal pain) age and gender. The molecular fingerprints of a selection of 39 isolates and 3 reference strains of P. shigelloides were highly variable and each had a unique profile. We conclude that although P. shigelloides infections are usually mild and self-limiting, this organism may contribute to a significant proportion of travellers' diarrhoea in the Orient. The species is characterized by great heterogeneity at the DNA level. PMID- 11218203 TI - Infection with verocytotoxin-producing Escherichia coli O157 during a visit to an inner city open farm. AB - Two cases of Escherichia coli O157 infection occurred in children after visiting an inner city open farm. Subsequently faecal samples collected from animal pens and samples of composted mixed animal manure and vegetable waste were examined for E. coli O157 by enrichment culture, immunomagnetic separation and culture of magnetic beads to cefixime tellurite sorbitol MacConkey agar. Strains of E. coli O157 were characterized by hybridization with DNA probes for VT1, VT2 and eaeA, plasmid profile analysis, phage typing and pulsed field gel electrophoresis (PFGE). Verocytotoxin-producing E. coli O157 strains were isolated from faecal samples from a cow, a horse, 3 breeds of pigs, 2 breeds of sheep and 2 breeds of goats and from 2 samples of compost which had been processed for 3 months. All strains were phage type 21, hybridized with probes for VT2 and eaeA but not with one for VT1, harboured 92 and 2 kb plasmids and gave indistinguishable banding patterns with PFGE. Although only two culture-confirmed cases of infection had been identified, the farm had over 100,000 visitors per year and so it was closed as a precaution both to allow a thorough investigation and to prevent further cases. The investigation identified many factors which may have contributed to transmission of E. coli O157 infection. Most of these were readily resolved by appropriate corrective measures and as there were no further cases associated with the farm during the ensuing 4 weeks it then re-opened. These cases highlight the risk, especially to young children, of acquiring zoonotic infections during visits to open farms and emphasize the need for adequate guidance and supervision before and during such visits. PMID- 11218204 TI - Genomic fingerprinting of shigatoxin-producing Escherichia coli (STEC) strains: comparison of pulsed-field gel electrophoresis (PFGE) and fluorescent amplified fragment-length polymorphism (FAFLP). AB - For epidemiological studies of shigatoxin-producing Escherichia coli (STEC) infections, rapid, reproducible and highly discriminative methods are required. In this study, we examined the performance of the fluorescent amplified-fragment length polymorphism (FAFLP) technique for epidemiological fingerprinting of STEC isolates and compared it to the acknowledged fingerprinting method pulsed-field gel electrophoresis (PFGE). A total of 88 STEC isolates, including 82 of serotype O157:H7 or O157:H-, were subjected to fingerprinting by both PFGE and FAFLP. The isolates included sporadic and epidemiologically related strains of both animal and human origin from widespread geographical locations. The FAFLP fingerprint patterns confirmed the clonal nature of STEC O157 strains. Among the 82 O157:H7/H isolates belonging to 49 distinct groups of epidemiological unrelated isolates, 24 FAFLP profiles and 51 PFGE patterns were obtained. Thus, PFGE had a higher discriminatory power than FAFLP and overall correlated better to available epidemiological data. Consequently, the PFGE technique remains the method of choice in epidemiological investigations of STEC infections. PMID- 11218205 TI - Population-based surveillance for bacterial meningitis in the Dominican Republic: implications for control by vaccination. AB - Quantifying the local burden of disease is an important step towards the introduction of new vaccines, such as Haemophilus influenzae type b (Hib) conjugate vaccine. We adapted a generic protocol developed by the World Health Organization for population-based surveillance of bacterial meningitis. All hospitals that admit paediatric patients with meningitis in the National District, Dominican Republic were included in the system and standard laboratory methods were used. The system identified 111 cases of confirmed bacterial meningitis. Hib was the leading cause of bacterial meningitis, followed by group B streptococcus, S. pneumoniae, and N. meningitidis. Unlike hospital-based case series, this population-based system was able to calculate incidence rates. The incidence of Hib meningitis was 13 cases per 100,000 children < 5 years old. The data from this study were used by the Ministry of Health to support the introduction of routine Hib vaccination and will be used to monitor its effectiveness. PMID- 11218206 TI - Determinants of case fatality rates of meningococcal disease during outbreaks in Makkah, Saudi Arabia, 1987-97. AB - We studied case-fatality rates (CFRs) among cases of meningococcal disease (MCD) admitted to Makkah (Saudi Arabia) hospitals during the period 1988-97. Of 483 cases, 431 (89.2%) were due to strains of serogroup A, 31 (6.4%) to serogroup W135, 16 (3.3%) to serogroup C, and 5 (10%) to serogroup B. Eighty-one patients died (case fatality rate (CFR)) 16.8%, 95% CI 13.5%, 20.4%). The CFR in infections due to serogroup A strains was 14.8%, and for other serogroups it was 32.7% (95% CI 20.3%, 47.1%). The CFR of MCD due to N. meningitidis serogroup A increased steadily with age (P<0.05). Seeking first medical help at a foreign Hajj medical mission and being treated in a non-specialized hospital were associated with a higher case fatality rate. PMID- 11218207 TI - Serotypes/groups distribution and antimicrobial resistance of invasive pneumococcal isolates: implications for vaccine strategies. AB - Based on the invasive pneumococcal isolates referred to reference laboratories in Scotland in 1988-99, we identified the distribution of serotypes/groups and their antimicrobial resistance patterns in order to evaluate the coverage of polysaccharide and the new pneumococcal conjugate vaccines. A total of 5659 invasive isolates were included. Of these, 5124 (90.5%) were blood isolates, 308 (5.5%) were CSF isolates, 143 (2.5%) were blood and CSF and 84 (1.5%) were other normally sterile isolates. The most prevalent 11 serotypes/groups were 14, 9, 19, 6, 23, 1, 3, 4, 7, 8 and 18, in numerical order. These accounted for 84% of total serotypes/groups. The serotypes/groups included in the 23 and 14-valent polysaccharide vaccines accounted for 96% and 88% of all isolates. Both vaccines accounted for 98% of penicillin non-susceptible and 100% of erythromycin non susceptible isolates. The 7, 9, and 11-valent conjugate vaccines covered 61, 68 and 80% of invasive isolates respectively. The coverage of these vaccines was substantially higher in youngest age group with 84, 86 and 93% of invasive isolates in children < 2 years included in the 7, 9 and 11-valent conjugate vaccines compared with 58, 64 and 77% in adults > or = 65 years of age. The serotype/group distribution of invasive isolates in Scotland varied from year to year over the period 1993-9. The coverage of the 23-valent vaccine remained above 95% in each year but the coverage of the 7, 9 and 11-valent conjugate vaccines showed more marked fluctuation with coverage as low as 53, 60 and 75% in some years. Continued surveillance of invasive pneumococcal isolates is required to inform the development of appropriate vaccine strategies to prevent pneumococcal disease in Scotland. PMID- 11218208 TI - The prevalence and clonal diversity of penicillin-resistant Streptococcus pneumoniae in Kuwait. AB - Penicillin-resistant Streptococcus pneumoniae (PRSP) is widespread all over the world, including countries previously free of PRSP. This study was undertaken to determine the prevalence, the common serotypes and the clonality of PRSP isolated over a period of 1 year, from various clinical samples from three major hospitals in Kuwait. Strains were identified by standard methods and their antibiotic susceptibility was determined by the agar dilution method. The clonality of the isolates was determined by repetitive extragenic palindromic sequence polymerase chain reaction (REP-PCR) genomic profiling and pulsed field gel electrophoresis (PFGE). Serotyping was done by Quellung reaction using specific antisera. We found that 55% of the S. pnuemoniae were resistant to penicillin (46% and 9% exhibited intermediate and full resistance, respectively). Nearly 41% were resistant to sulfamethoxazole-trimethoprim, 9% to cefotaxime and ceftriaxone, 15% to amoxycillin-clavulanate, 17% to cefuroxime, 77 % to cefaclor, and 14% to clindamycin. The commonest serotypes among the PRSPs were 6A, 6B, 14, 19F, 23F and nontypable. PFGE and REP-PCR patterns showed a large diversity of genetic clones of the PRSP. Serotypes 6B, 14, 19F and 23F were more clonally related than the others. Our data showed that the prevalence of PRSP was high, the serotypes were diversified and different genetic clones make up the population of circulating PRSP in Kuwait. PMID- 11218209 TI - Dynamics of natural immunity caused by subclinical infections, case study on Haemophilus influenzae type b (Hib). AB - Natural immunity to Haemophilus influenzae type b (Hib) is based primarily on antibodies that are thought to develop in response to subclinical infections. Wide use of conjugated Hib vaccines could lead to decreases in circulating Hib bacteria, thereby diminishing antibody levels in the unvaccinated. We applied a statistical model to estimate the duration of natural immunity to Hib under different forces of infection. Prior to the introduction of conjugated Hib vaccines, new Hib infections were estimated to occur once in 4 years and the antibody concentration to stabilize at a level around 1 microg/ml. In the absence of new stimuli, i.e. infection, 57% of the unvaccinated population would become susceptible to invasive disease (antibody levels < 0.15 microg/ml) in 10 years. Due to an interaction between the force of infection and the duration of immunity, in some situations numbers of invasive infections could increase in unvaccinated cohorts. This theoretical scenario has yet to be observed in practice. PMID- 11218210 TI - Serodiagnosis of human plague by an anti-F1 capsular antigen specific IgG/IgM ELISA and immunoblot. AB - Plague is a re-emerging disease endemic in at least 24 countries. Non-endemic countries should be able to confirm plague to prevent outbreaks due to imported cases. We established a combination of a IgG/IgM screening ELISA and a confirmation immunoblot employing F1 capsular antigen (CA) for the serodiagnosis of plague in countries where yersiniosis is present. The ELISA and the immunoblot assay showed a specificity of 96.1% and 100% among sera from healthy German blood donors. This group had a seroprevalence of 39% of anti-yersinia outer protein (YOP) antibodies obviously caused by previous Y. enterocolitica infection. The ELISA detected anti-F1 CA antibodies in 22 and the immunoblot in 20 out of 26 sera of plague vaccinees. Five control sera from bacteriologically confirmed plague cases from Madagascar reacted positively. It can be concluded that anti YOP antibodies do not affect assays based on purified F1 CA. PMID- 11218211 TI - Strengths and limitations of molecular subtyping in a community outbreak of Legionnaires' disease. AB - An epidemiological and microbiological investigation of a cluster of eight cases of Legionnaires' disease in Los Angeles County in November 1997 yielded conflicting results. The epidemiological part of the investigation implicated one of several mobile cooling towers used by a film studio in the centre of the outbreak area. However, water sampled from these cooling towers contained L. pneumophila serogroup 1 of another subtype than the strain that was recovered from case-patients in the outbreak. Samples from two cooling towers located downwind from all of the case-patients contained a Legionella strain that was indistinguishable from the outbreak strain by four subtyping techniques (AP-PCR, PFGE, MAb, and MLEE). It is unlikely that these cooling towers were the source of infection for all the case-patients, and they were not associated with risk of disease in the case-control study. The outbreak strain also was not distinguishable, by three subtyping techniques (AP-PCR, PFGE, and MAb), from a L. pneumophila strain that had caused an outbreak in Providence, RI, in 1993. Laboratory cross-contamination was unlikely because the initial subtyping was done in different laboratories. In this investigation, microbiology was helpful for distinguishing the outbreak cluster from unrelated cases of Legionnaires' disease occurring elsewhere. However, multiple subtyping techniques failed to distinguish environmental sources that were probably not associated with the outbreak. Persons investigating Legionnaires' disease outbreaks should be aware that microbiological subtyping does not always identify a source with absolute certainty. PMID- 11218212 TI - Lack of serological evidence for Mycoplasma fermentans infection in army Gulf War veterans: a large scale case-control study. AB - Mycoplasma firmentans is suspected in the development of 'Gulf War illness' in veterans of Operation Desert Storm. We conducted a matched case-control study for the prevalence of M. firmentans-specific antibodies before and after the operation, as well as seroconversion rates in veterans with and without complaints of 'Gulf War illness'. Cases consisted of Gulf War veterans, who complained of various illnesses and were enrolled in the second phase of the health evaluation by the Army Comprehensive Clinical Examination Program (CCEP). Controls were selected from Gulf War veterans who did not participate in the registry and did not request a health evaluation by the CCEP. Before operation deployment, 34 out of 718 of the cases (48%) and 116 out of 2233 of the controls (5.2%) tested positive for M. fermentans-specific antibodies. There was no difference in rates of seroconversion between cases and controls (1.1 vs. 1.2%) to M. fermentans during Operation Desert Storm. Thus, there is no serological evidence that suggests infectionby M. fermentans is associated with development of 'Gulf War illness'. PMID- 11218213 TI - Modelling rubella in Europe. AB - The prevention of congenital rubella syndrome (CRS), as a complication of rubella infection during pregnancy, is the main aim of rubella vaccination programmes. However, as vaccination of infants leads to an increase in the average age at which those who were not immunized become infected, certain rubella vaccination programmes can lead to an increase in the incidence of CRS. In this paper we use a mathematical model of the transmission dynamics of rubella virus to investigate the likely impact of different vaccination policies in Europe. The model was able to capture pre- and post-vaccination patterns of infection and prevalence of serological markers under a wide variety of scenarios, suggesting that the model structure and parameter estimates were appropriate. Analytical and numerical results suggest that endemic circulation of rubella is unlikely in Finland, the United Kingdom, The Netherlands, and perhaps Denmark, provided vaccine coverage is uniform across geographical and social groups. In Italy and Germany vaccine coverage in infancy has not been sufficient to interrupt rubella transmission, and continued epidemics of CRS seem probable. It seems unlikely that the immunization programmes in these countries are doing more harm than good, but this may be partly as a result of selective immunization of schoolgirls. Indeed, in both these countries, selective vaccination of schoolgirls with inadequate vaccination histories is likely to be an important mechanism by which CRS incidence is suppressed (unlike the other countries, which have had sufficiently high infant coverage rates to withdraw this option). Reducing inequalities in the uptake of rubella vaccine may bring greater health benefits than increasing the mean level of coverage. PMID- 11218214 TI - The pre-vaccination epidemiology of measles, mumps and rubella in Europe: implications for modelling studies. AB - Data on the pre-vaccination patterns of infection for measles, mumps and rubella are collated from a number of European countries in order to compare the epidemiology of the three viruses. Key epidemiological parameters, such as the age-specific force of infection and the basic reproduction number (R0) are estimated from case notification or serological data using standard techniques. A method is described to compare force of infection estimates derived from serological data. Analysis suggests that the pre-vaccination patterns of measles and mumps infection in the different countries were similar. In contrast, the epidemiology of rubella was highly variable between countries. This suggests that it may be acceptable to use parameter values estimated from other countries to model measles and mumps transmission, but that this approach to modelling rubella transmission requires more caution. Estimates of R0 depend on underlying mixing assumptions. Constraints were placed on R0 estimates by utilising knowledge of likely mixing patterns. The estimates for R0 were highest for measles, intermediate for mumps, and generally lowest for rubella. Analysis of within- and between-age-group transmission rates suggested that mumps transmission tends to be more concentrated within young children than the other two viruses. The implications for the design of immunization programmes are that mumps may be the easiest to control via infant immunization since it is predominantly transmitted between the very young and the variability in rubella epidemiology requires that careful consideration of the possible effects of vaccination options should be made using local data when planning rubella immunization programmes. PMID- 11218215 TI - Modelling the impact of immunization on the epidemiology of varicella zoster virus. AB - The objective of this study was to develop and apply a dynamic mathematical model of VZV transmission to predict the effect of different vaccination strategies on the age-specific incidence and outcome of infection. To do so a deterministic realistic age-structured model (RAS) was used which takes account of the increased potential for transmission within school aged groups. Various vaccine efficacy scenarios, vaccine coverages and vaccination strategies were investigated and a sensitivity analysis of varicella incidence predictions to important parameters was performed. The model predicts that the overall (natural and breakthrough) incidence and morbidity of varicella would likely be reduced by mass vaccination of 12-month-old children. Furthermore, adding a catch-up campaign in the first year for 1-11 year olds seems to be the most effective strategy to reduce both varicella incidence and morbidity (in the short and long term), though with the possible detrimental effect of increasing the incidence of zoster. PMID- 11218216 TI - Serological and virological evidence of non-sexual transmission of human herpesvirus type 8 (HHV8). AB - To evaluate whether or not human herpesvirus 8 (HHV8) can be transmitted through a non-sexual route a serological survey was carried out in a group of 51 catholic nuns. The seroprevalence rate and the geometrical mean antibody titre to anti latent HHV8 antigen were similar in nuns and in a group of 60 women, matched by age, in the general population (27 vs. 24%; 1028 vs. 1575, respectively). Moreover, by using nested polymerase chain reaction (PCR), HHV8 DNA sequences were detected in 7 of 16 (43.8%) saliva and peripheral blood mononuclear cells (PBMC) from patients with classical Kaposi's sarcoma (KS) and in 3 out of 7 (42%) AIDS-KS patients. None of 5 HIV positive persons who did not have KS tested positive for HHV8 DNA. HHV8 DNA sequences were also detected in 2 of 12 (17%) saliva and 1 PBMC sample out of 12 healthy HHV8 positive individuals (age range: 30-80 years old). This paper suggests that non-sexual transmission of HHV8 is operating in our geographical setting and saliva may be a potential source of HHV8 spreading in the general population. PMID- 11218218 TI - Herpes simplex virus type-2 antibodies in pregnant women: the impact of the stage of pregnancy. AB - In this study the impact of pregnancy duration on the measured level of HSV-2 antibodies was assessed. The study population comprised 35,940 pregnant women in Norway, in 1992-4, followed during pregnancy. A random sample of 960 women was selected. A mean of 2.6 serum samples from each woman were analysed for HSV-2 specific IgG antibodies at different times in pregnancy. Crude and adjusted odds ratios were estimated in logistic regression models taking all observations per women into account. Twenty-seven percent of the pregnant women had antibodies against HSV-2 in the first trimester. The adjusted odds ratio of being HSV-2 antibody positive decreased during the pregnancy and was 0.5 (0.2-0.9, 95% confidence interval) in the 40th as compared to the 10th week of pregnancy. About 50% of initially HSV-2 positive women did not have detecable antibodies by the end of the pregnancy. This may be explained by haemodilution during pregnancy. Our findings have diagnostic implications and should encourage further studies. PMID- 11218217 TI - Incidence, seasonality and serotypes of rotavirus in Gipuzkoa (Basque Country), Spain. A 14-year study. AB - Over a 14-year period (1984-97) the presence of rotavirus in stool samples from children under 15 years with acute gastroenteritis was studied by enzymoimmunoanalysis. Serotyping (G1-G4) was performed using monoclonal antibodies. A total of 17,348 children under 15 were investigated. Rotavirus was detected in 3637 (21.0%) specimens, 74.6% of which were from children younger than 2 years old. G1 and G4 were the most frequent serotypes. In 1991-7, the minimum incidence of rotavirus gastroenteritis in children under 4 years of age was 21.7 cases/1000 children/year. By the age of 5 years, at least 1 out of 11.3 children and probably 1 out of every 5-6 children in this area had experienced an episode of rotavirus gastroenteritis that required medical care. In the 1984-90 period a clear seasonality was not observed but in the second period of the study (1991-7), seasonality was marked, with peak activity in winter. PMID- 11218219 TI - A severe and explosive outbreak of hepatitis B in a rural population in Sirsa district, Haryana, India: unnecessary therapeutic injections were a major risk factor. AB - Most outbreaks of viral hepatitis in India are caused by hepatitis E. This report describes an outbreak of hepatitis B in a rural population in Haryana state in 1997. At least 54 cases of jaundice occurred in Dhottar village (population 3096) during a period of 8 months; 18 (33.3%) of them died. Virtually all fatal cases were adults and tested positive for HBsAg (other markers not done). About 88% (21/24) of surviving cases had acute or persistent HBV/HCV infections; 54% (13/24) had acute hepatitis B. Many other villages reported sporadic cases and deaths. Data were pooled from these villages for analysis of risk factors. Acute hepatitis B cases had received injections before illness more frequently (11/19) than those found negative for acute or persistent HBV/HCV infections (3/17) (P = 0.01). Although a few cases had other risk factors, these were equally prevalent in two groups. The results linked the outbreak to the use of unnecessary therapeutic injections. PMID- 11218220 TI - Prevalence of hepatitis B anti-core antibody in the Republic of Ireland. AB - The aim of this study was to estimate the prevalence of hepatitis B exposure in the population of the Republic of Ireland, by measuring the prevalence of hepatitis B anti-core antibody in oral fluid collected by postal survey. A random multi-stage stratified sample of Irish households was obtained, using the Irish electoral register as the sampling frame. A total of 962 households were selected, and a household response rate of 60.4% was achieved. Oral fluid specimens totalling 1714 were tested for antibody to hepatitis B core antigen (anti-HBc), using an Immune Capture Enzyme Immuno-Assay. Five specimens (0.29%) were found to contain anti-HBc. Adjusting for study design, the estimated anti HBc prevalence in the Republic of Ireland is 0.51%. This study demonstrates that self-collection of oral fluid samples is acceptable to the public, and based upon the data generated, that the Republic of Ireland has a low prevalence of hepatitis B infection. PMID- 11218221 TI - The prevalence and genetic diversity of hepatitis C infection in antenatal clinic attenders in two regions of England. AB - The prevalence and genetic diversity of hepatitis C infection in women attending antenatal clinics in two regions of England was investigated to inform future surveillance and control measures. Women booking into antenatal care are routinely offered a test for immunity to rubella. Serum residues from these tests were unlinked, anonymized and archived as part of the Unlinked Anonymous Prevalence Monitoring Programme (UAPMP). The serum specimens were tested for anti HCV using a cost-effective pooling strategy. After taking into account differential sampling from the UAPMP serum archive, the adjusted overall prevalence of anti-HCV was 0.43% (95% CI: 0.32-0.53) in London and 0.21% (95% CI: 0.14-0.28) in the Northern and Yorkshire region. Restriction fragment length polymorphism of amplified HCV RNA identified type 3a as the most common HCV genotype in these antenatal women. The prevalence of anti-HCV in antenatal women in the UK is low and consistent with that expected from injecting drug use. PMID- 11218222 TI - Modelling the impact of prior immunity, case misclassification and bias on case control studies in the investigation of outbreaks of cryptosporidiosis. AB - Cryptosporidiosis is the most common cause of outbreaks of disease linked to mains water supply in the United Kingdom and the second commonest in the United States. Recent evidence has suggested that prior population immunity may have an impact on the epidemiology of waterborne outbreaks and in particular prior immunity may reduce the power of case-control studies for demonstrating association between disease and water consumption behaviour. However, the degree of impact of prior immunity on the power of epidemiological studies is not yet clear. This paper reports the results of some simple mathematical models of outbreaks of waterborne disease in populations with varying levels of immunity due to prior water and non-water exposure. The basic outbreak model was run on a spreadsheet. To determine the impact of prior immunity on case-control studies, further analysis was done using a Monte Carlo method to simulate sampling from cases and controls. It was found that moderate degrees of prior immunity due to water associated disease could markedly reduce the relative risk of water consumption on illness in waterborne outbreaks. In turn this would reduce the power of case-control studies. In addition, this model was used to demonstrate the impact of case misclassification and recall bias on case-control studies. Again it was found that within the model, the results of case-control studies could be significantly affected by both these sources of error. Anyone conducting epidemiological investigations of potentially waterborne outbreaks of disease should be aware of the epidemiological problems. Mistakes from case-control studies will be minimized if the outbreak team pays considerable attention to the descriptive phase of the investigation and if case-control studies are conducted as soon as possible after an outbreak is detected. PMID- 11218223 TI - The prevalence of viral antibodies during a large population fluctuation of house mice in Australia. AB - We studied the seroprevalence of three viruses (mouse cytomegalovirus (MCMV), minute virus of mice (MVM), and mouse parvovirus (MPV)) in house mice (Mus domesticus) in 1995 7. In the first year average mouse density was less than 1 mouse/ha. From November 1995 to May 1996 the population increased at an average rate of 7% per week, a doubling time of about 10 weeks. From August 1996 to May 1997 the population increased at an average rate of 10% per week, a doubling time of about 7.5 weeks. From a peak around 250 mice/ha in May 1997, the mouse population fell 19% per week to 5 mice/ha in October 1997. The seroprevalence for all three viruses varied dramatically over time. MCMV had the highest seroprevalence (61.7%), followed by MVM (8.5%) and MPV (18.4%). Time series data indicated that MCMV spread rapidly through the population of mice once trap success was greater than 14% (40-100 mice/ha). By contrast MVM and MPV seroprevalence occurred with a 2-3 month and 3-4 month time lag, respectively. The current study supports the contention that MCMV would be a good carrier for an immunocontraceptive vaccine for controlling field populations of mice. PMID- 11218224 TI - Genetic analysis of foot-and-mouth disease virus type O isolates responsible for field outbreaks in India between 1993 and 1999. AB - Partial nucleotide sequence at the 3' end of ID (VP1-encoding) gene of 90 foot and-mouth disease virus type O isolates recovered from field outbreaks in India between 1993-9 were determined. The sequences were compared with each other and reference viruses. The published sequences of 15 type O isolates recovered from different parts of Asia and one isolate (O1BFS) from Europe and one from Egypt (O1/Sharquia/Egypt/72) were also included in the analysis for comparison. On the basis of phylogenetic analysis the viruses could be grouped into four distinct genotypes (genotypes I-IV). All 90 isolates from India were genotype-I, as were the reference isolates from Bangladesh, China, Egypt, Iran, Saudi Arabia, Syria and Turkey. Genotype-I isolates were further subdivided into 16 sub-genotypes. The Indian isolates were found to be extremely heterogeneous in nature and clustered into 12 different genetic groups. In genotype-I, the nucleotide sequence difference seen between the isolates was 0-11.6%, while among the Indian isolates it is 0-8.8%. Viruses of similar genetic groups are circulating in India, Bangladesh and countries of the Middle East. Genotype-II and -III are represented by isolates from Lebanon (O1/South Lebanon) and Europe (O1-BFS), respectively. Genotype-IV is formed by isolates from China, Hong Kong and Taiwan. The present study reveals the occurrence of viruses belonging to multiple genetic groups over a short period of time and persistence of single genetic group in the same geographical area over several years. This is consistent with the endemic nature of the disease in the country. PMID- 11218225 TI - Interaction of procedural factors in human performance on yoked schedules. AB - The differential effects of reinforcement contingencies and contextual variables on human performance were investigated in two experiments. In Experiment 1, adult human subjects operated a joystick in a video game in which the destruction of targets was arranged according to a yoked variable-ratio variable-interval schedule of reinforcement. Three variables were examined across 12 conditions: verbal instructions, shaping, and the use of a consummatory response following reinforcement (i.e., depositing a coin into a bank). Behavior was most responsive to the reinforcement contingencies when the consummatory response was available, responding was established by shaping, and subjects received minimal verbal instructions about their task. The responsiveness of variable-interval subjects' behavior varied more than that of variable-ratio subjects when these contextual factors were altered. Experiment 2 examined resistance to instructional control under the same yoked-schedules design. Conditions varied in terms of the validity of instructions. Performance on variable-ratio schedules was more resistant to instructional control than that on variable-interval schedules. PMID- 11218226 TI - Drug discrimination: stimulus control during repeated testing in extinction. AB - Rats were trained, under a two-lever drug-discrimination procedure, to respond differentially depending upon whether lorazepam (1.0 mg/kg) or no injection had been administered before the session. Responses on the appropriate lever produced a food pellet under a modified fixed-ratio (FR) 10 schedule, in which the 10 responses had to be emitted consecutively. In reinforcement tests, completing an FR 10 on either lever produced a pellet. In extinction tests, stimulus changes paired with reinforcement occurred but no pellet was delivered. Training sessions were conducted between test sessions. Each of four extinction phases consisted of six tests preceded by one stimulus (e.g., lorazepam). Repeated exposures to extinction reduced response rates for all rats, but stimulus control, as inferred from either percentage of total responses or percentage of total FR 10s on the drug-appropriate lever, remained high. The percentage of total FR 10s measure was less subject to skewing under low-rate conditions than was the percentage of total responses measure and provided an evaluation of stimulus control in terms of meeting the consecutive response contingency. These results demonstrate a level of independence between response rate and stimulus control in drug discrimination, which has positive implications for the validity of interpreting discriminative effects of novel test conditions in well-trained animals, even when overall response rates are low. PMID- 11218227 TI - Effect of drugs on response-duration differentiation VII: response-force requirements. AB - Rats were trained to press a lever for at least 1 s but for less than 1.3 s. The force required to press the lever was then increased or decreased by 10, 15, or 20 g. Increases in the force requirements for lever pressing decreased timing accuracy, but decreases in the force requirement had the opposite effect. Accuracy decreases at increasing force requirements were characterized by an increase in the relative frequency of responses that were too short to meet the reinforcement criterion. In contrast, increases in accuracy when the force requirements were decreased were characterized by increases in response durations that met the reinforcement criterion and decreases in the relative frequency of responses that were too short to produce the reinforcer. Phencyclidine (PCP) and methamphetamine produced dose-dependent decreases in accuracy that were associated primarily with increases in the relative frequency of short response durations, although methamphetamine also produced increases in long response durations at some doses. When the effects of PCP were determined with the force requirement increased by 10 g or decreased by 15 g, the cumulative response duration distribution shifted toward even shorter response durations. When the effects of methamphetamine were determined with the force requirement on the lever increased by 10 g, the cumulative frequency distribution was shifted toward shorter response durations to about the same extent as it had been before force requirements increased; however, when the force required to press the lever was decreased by 15 g, these shifts toward shorter response durations almost completely disappeared. These results show that increases and decreases in the force requirements for lever pressing have different effects on the accuracy of temporal response differentiation. PMID- 11218228 TI - Choice, changing over, and reinforcement delays. AB - In three experiments, pigeons were used to examine the independent effects of two normally confounded delays to reinforcement associated with changing between concurrently available variable-interval schedules of reinforcement. In Experiments 1 and 2, combinations of changeover-delay durations and fixed interval travel requirements were arranged in a changeover-key procedure. The delay from a changeover-produced stimulus change to a reinforcer was varied while the delay between the last response on one alternative and a reinforcer on the other (the total obtained delay) was held constant. Changeover rates decreased as a negative power function of the total obtained delay. The delay between a changeover-produced stimulus change had a small and inconsistent effect on changeover rates. In Experiment 3, changeover delays and fixed-interval travel requirements were arranged independently. Changeover rates decreased as a negative power function of the total obtained delay despite variations in the delay from a change in stimulus conditions to a reinforcer. Periods of high-rate responding following a changeover, however, were higher near the end of the delay from a change in stimulus conditions to a reinforcer. The results of these experiments suggest that the effects of changeover delays and travel requirements primarily result from changes in the delay between a response at one alternative and a reinforcer at the other, but the pattern of responding immediately after a changeover depends on the delay from a changeover-produced change in stimulus conditions to a reinforcer. PMID- 11218229 TI - Behavior analysis and revaluation. AB - Revaluation refers to phenomena in which the strength of an operant is altered by reinforcer-related manipulations that take place outside the conditioning situation in which the operant was selected. As an example, if lever pressing is acquired using food as a reinforcer and food is later paired with an aversive stimulus, the frequency of lever pressing decreases when subsequently tested. Associationist psychology infers from such findings that conditioning produces a response-outcome (i.e., reinforcer) association and that the operant decreased in strength because pairing the reinforcer with the aversive stimulus changed the value of the outcome. Here, we present an approach to the interpretation of these and related findings that employs neural network simulations grounded in the experimental analysis of behavior and neuroscience. In so doing, we address some general issues regarding the relations among behavior analysis, neuroscience, and associationism. PMID- 11218230 TI - Criticisms of the satiety hypothesis as an explanation for within-session decreases in responding. AB - The authors of four papers recently reported that satiation provides a better explanation than habituation for within-session decreases in conditioned responding. Several arguments question this conclusion. First, the contribution of habituation to within-session changes in responding seems clearly established. Information that is consistent with habituation, but that is difficult to reconcile with satiation, is not adequately addressed. Second, the limited evidence offered in support of satiation is ambiguous because the results are just as compatible with habituation as with other satiety variables. Finally, the term satiation is used in an intuitive way that is sometimes contradicted by research about the termination of ingestion. Use of the technical term satiation in a way that differs from its conventional usage will only isolate operant psychology from other areas of psychological research. PMID- 11218231 TI - Experimental analysis of human vocal behavior: applications of speech-recognition technology. AB - Recent developments in speech recognition make it feasible to apply the technology to study vocal behavior. The present study illustrates the use of this technology to establish functional stimulus classes. Eight students were taught to say nonsense words in the presence of arbitrarily assigned sets of symbols consistent with three three-member experimenter-defined stimulus classes. Computer-controlled speech-recognition software was used to record, analyze, and differentially reinforce vocal responses. When the stimulus classes were established, students were taught to say a new nonsense word in the presence of one member of each stimulus class. Transfer of function was tested subsequently to determine if the novel stimulus names transferred to the remaining stimulus class members. Most subjects required two iterations of the training and testing procedures before transfer occurred. The data illustrate the usefulness of recording vocal behavior during stimulus control procedures and demonstrate the use of speech-recognition technology. The paper also describes the current state of speech-recognition technology and suggests several other areas of research that might benefit from using vocal behavior as its primary datum. PMID- 11218232 TI - Pulse oximetry saturation levels during routine unsedated diagnostic upper gastrointestinal endoscopy. AB - BACKGROUND: Diagnostic procedures account for over 90% of all upper gastrointestinal endoscopies. Pulse oximetry saturation (SpO2) levels were assessed in patients attending for routine unsedated diagnostic gastroscopy to identify factors associated with oxygen desaturation. METHODS: Three hundred and thirty unsedated patients were monitored with continuous pulse oximetry. A further 154 patients who requested sedation prior to endoscopy were studied as a positive control group. RESULTS: SpO2 levels were lower in sedated compared to unsedated patients (P < 0.0001). Six unsedated patients (2%) desaturated to 90% or less during endoscopy compared to 32 sedated patients (21%) (P < 0.0001). SpO2 levels in unsedated patients were not related to patient sex, age, cigarette smoking, endoscope diameter, basal SpO2 levels or duration of endoscopy. In contrast, examination of the pharyngeal area and epiglottis (P = 0.0002) and a longer intubation time (P = 0.0002) were associated with lower SpO2 levels. The lowest SpO2 level recorded during unsedated endoscopy was 88%. CONCLUSION: Pulse oximetry is not a prerequisite to performing routine unsedated diagnostic gastroscopy in patients without severe systemic disease. PMID- 11218233 TI - Ascites caused by brucellosis: a report of two cases. AB - Brucellosis is a zoonosis still endemic in developing areas of the world. Focal complications of Brucellosis are well known and often troubling in the differential diagnosis. Gastrointestinal complications of Brucellosis are randomly reported, ascites being particularly rare, and usually in the context of a predisposing condition such as cirrhosis. We describe two cases of ascites attributed to Brucellosis, one in a previously healthy patient with an accompanying clinical picture of acute Brucellosis, in whom ascites reflected the response of the peritoneal mononuclear phagocytic system, and one in a HBsAg positive, but not cirrhotic, patient, in whom Brucellosis seemed to act as a trigger effect for the development of ascites. Both cases of ascites were of an effusion type, with a predominantly lymphocytic cell count, and exhibited an excellent response to treatment with tetracycline and rifampicin. PMID- 11218234 TI - Involvement of cyclic GMP in nitric-oxide-induced gastric relaxation Comparison of the actions of cyclic GMP and cyclic AMP. AB - BACKGROUND: Smooth muscle relaxation induced by various agents that increase the cellular levels of cyclic nucleotides (cAMP and cGMP) is accompanied by a decrease in intracellular Ca2+ concentration. However, little is known about the differences between the inhibitory effects of cAMP and cGMP on the contraction of smooth muscle. OBJECTIVE: To compare the effects and underlying mechanisms of cAMP and cGMP on the inhibition of gastric smooth muscle contraction, cyclic nucleotide promoting agents, as well as cell membrane permeable cyclic nucleotides were used. METHODS: Isometric contraction was measured from circular muscle strips prepared from the fundus of cat stomach in a cylinder-shaped chamber filled with Krebs-Ringer solution (pH 7.4, temperature 36 degrees C) bubbled with 5% CO2 in O2. The level of inositol phosphates (IPs) was measured. RESULTS: Forskolin and sodium nitroprusside significantly inhibited acetylcholine (ACh)-induced gastric smooth muscle contraction and increased the cellular levels of cAMP and cGMP, respectively. Direct application of 8-Br-cAMP and 8-Br-cGMP also significantly inhibited ACh-induced contraction. Both verapamil and TMB-8 inhibited ACh-induced contraction. The combined inhibitory effect of verapamil and TMB-8 was significantly greater than the effect of either one, separately. Forskolin or sodium nitroprusside similarly augmented the effect of verapamil. However, the inhibitory effect of TMB-8 was augmented only by 8-Br-cGMP or sodium nitroprusside but not by 8-BrcAMP or forskolin. Forskolin and 8-Br-cAMP significantly inhibited the formation of inositol phosphates stimulated by ACh. CONCLUSIONS: cAMP inhibits the contraction mechanism associated with intracellular Ca2+ mobilization as well as extracellular Ca2+ influx, while cGMP inhibits contraction by inhibiting the mechanism associated with extracellular Ca2+ influx. PMID- 11218235 TI - A critical review of epidemiological studies in inflammatory bowel disease. AB - This review addresses the difficulty in interpreting the results of epidemiological studies in IBD and in making meaningful comparisons between studies. Both ulcerative colitis and Crohn disease appear to be more common in some industrialized countries such as Scandinavia, United Kingdom, North America and less common in Central and Southern Europe, Asia and Africa. Given data showing an increased incidence of ulcerative colitis in the United Kingdom, it is crucial that more studies be conducted in developing countries. While the incidence of Crohn disease has increased strikingly in many areas, the incidence of ulcerative colitis has remained fairly stable in most. This could be due to the rising number of community-based studies, as well as the improved accuracy in diagnosing Crohn disease. Although, the incidence of IBD among Blacks in Africa is low, infection rates are high, life expectancy is lower than in developed countries. Data from the USA suggest that rates are similar in Afro-American and Caucasian populations. Rates for Jewish populations may be slightly higher than in non-Jewish populations but this also varies geographically. Careful attention to genetic, environmental, and socioeconomic factors must be accounted for in these studies. There is no strong evidence to support that IBD is more common in urban than in rural settings and migration towards more accessible health care has not been adequately addressed. Recent epidemiological studies suggest that mortality rates for IBD are similar to that of the general population for the majority of patients. However, older patients with IBD and newly diagnosed cases with severe diseases are at increased risk of dying. Epidemiological studies remain important in assisting with health policy planning and in hypothesis testing of etiological factors. As better diagnostic techniques become widely available and public health registries are increasingly used, it is possible that geographic differences will diminish. International collaborative studies will be better equipped to answer research questions addressing risk factors and disease natural history. We have summarized in Table V the essential criteria to conduct a sound epidemiological study, which would permit future testing of hypotheses among different populations. PMID- 11218236 TI - Decreased expression of epidermal growth factor receptor and mRNA of its ligands in Helicobacter pylori-infected gastric mucosa. AB - BACKGROUND: Epidermal growth factor (EGF) and TGF-alpha play a central role in maintaining gastric mucosal integrity. Little is known about the regulative role of the four other widely expressed epidermal growth factor receptor ligands, heparin-binding EGF, amphiregulin, betacellulin and cripto in the gastric mucosa. METHODS: Nineteen patients with Helicobacter pylori-positive gastritis and 32 healthy controls were investigated. Mucosal mRNA expression of EGF receptor ligands was determined by quantitative PCR before and after H. pylori eradication. PCR products were analyzed by soft laser scanning densitometry. Moreover, the effect of chronic active gastritis on EGF receptor expression was assessed by [125I] EGF receptor autoradiography. Immunohistochemistry was performed for TGF-alpha to localize growth factor expression. RESULTS: Antral and oxyntic biopsies showed strong mRNA expressions for TGF-alpha, amphiregulin and heparin binding EGF, but not for EGF, cripto and betacellulin. mRNA expression was significantly reduced down to 50% in H. pylori infection, significantly lower compared to normal gastric mucosa, and increased after eradication therapy. Moreover, chronic gastritis was associated with decreased antral EGF receptor binding compared to healthy controls, possibly reflecting reduced autoinduction. Immunohistochemical analyses localized TGF-alpha in the cytoplasma of gastric epithelial cells and revealed its increased expression after H. pylori eradication. CONCLUSIONS: The data presented suggest that amphiregulin, heparin binding EGF and TGF-alpha are important EGF receptor ligands in the gastric mucosa. H. pylori infection apparently suppresses their mRNA as well as receptor expression that is reversed by H. pylori eradication. This deficiency of the gastroprotective EGF system may contribute to the gastric pathogenicity of H. pylori infection. PMID- 11218237 TI - Motor and sensory function of the rectum in different subtypes of constipation. AB - BACKGROUND: It is not known whether evaluation of motor and sensory function of the rectum using a barostat may help to distinguish subtypes of constipation. METHODS: Motor and sensory function of the rectum have been evaluated using a barostat in 14 patients with slow transit constipation (STC), 12 patients with constipation-predominant irritable bowel syndrome (IBS) and 18 healthy controls. First minimal distending pressure was determined, after which spontaneous adaptive relaxation of the rectum was monitored. Then a step-wise isobaric distension procedure was performed, during which symptom perception was determined. The distension was followed by a 90-min barostat procedure: for 30 min in the basal state followed by ingestion of a semi-liquid meal (postprandial state). RESULTS: Minimal distending pressure was not different between both patient groups and controls, neither was compliance different between constipated patients and controls. The degree of spontaneous adaptive relaxation was in the same range in all groups. During distensions with high pressures, the perception of urge was significantly reduced in STC patients compared to IBS and controls, while the perception of pain was significantly increased in IBS versus STC and controls. Postprandially, a small decrease of rectal volume was only observed in the control group, but not in the patients. CONCLUSIONS: Rectal motor characteristics are not different between patients with constipation-predominant IBS, patients with STC and healthy controls while during isobaric distensions, sensations of urge were reduced in STC and sensations of pain were increased in IBS. Rectal visceroperception testing may help distinguish groups of patients with different subtypes of constipation. PMID- 11218238 TI - Programmed cell death in rat intestine: effect of feeding and fasting. AB - BACKGROUND: The regulation of intestinal cell death by luminal factors is poorly understood. The objectives of this study were to determine whether a diurnal rhythm of intestinal apoptosis exists, and to determine the role that feeding and fasting play in this process. METHODS: Mucosal apoptotic death was measured in fed and 24-h fasted rats and at various times after feeding by DNA fragmentation and in situ immunohistochemical staining (TUNEL). RESULTS: In 24-h fasted rats, 32% of total mucosal DNA was fragmented as compared to 9% in fed animals. In both jejunal and ileal segments, the fragmented DNA exhibited characteristic apoptotic DNA ladders on agarose gels. Immunohistochemical staining revealed significant location of apoptotic cells at the upper third of the intestinal villus. In the duodenum, DNA fragmentation at 6-12 h post feeding was 20% and decreased to 4% at 24 h. In comparison, DNA fragmentation in the jejunum and ileum was low from 0 to 6 h post feeding (2%-9%) and significantly increased at 12 h (18% versus 12%) and 24 h (30% versus 32%), respectively. These results are consistent with a temporal relationship between percent fragmented DNA and time after feeding with greater cell death at longer fasting period. A postprandial rhythm of DNA fragmentation was evident in the jejunum and ileum, in which fragmentation was at a peak between 0900 h and 1200 h. CONCLUSION: Collectively, the data show that initiation of apoptosis in apical enterocytes is coincident with cessation of feeding and commencement of fasting, and is consistent with a rhythm of programmed cell death in these cells that parallels the cyclical pattern of feeding and fasting. PMID- 11218239 TI - Effect of high-dose growth hormone and glutamine on body composition, urine creatinine excretion, fatty acid absorption, and essential fatty acids status in short bowel patients: a randomized, double-blind, crossover, placebo-controlled study. AB - BACKGROUND: Positive effects of high dose growth hormone and glutamine (GH + GLN) on body composition in short bowel patients have been described. Lack of effects on intestinal absorption found in some studies has been ascribed to concomitant essential fatty acid (EFA) deficiency. This study describes changes in body weight (BW) and composition, 24-h urine creatinine excretion, intestinal fatty acid absorption (total, saturated, unsaturated and EFA), and EFA status in relation to treatment with GH + GLN in 8 short bowel patients. METHODS: A double blind, crossover study between placebo and growth hormone (mean, 0.12 mg/kg/day) plus oral (mean, 28 g/day) and parenteral glutamine (mean, 5.2 g/day) for 28 days. Body composition was measured by dual-energy absorptiometry (DEXA) scans. Intestinal fatty acid absorption was evaluated in balance studies, and EFAs were measured in plasma phospholipids by gas liquid chromatography. RESULTS: Active treatment did not increase BW, lean body mass (LBM), fat mass (FM) and bone mass significantly compared with placebo treatment, but BW increased 1.03 kg (1.7%, P < 0.05), LBM 2.93 kg (8.7%, P < 0.001) and FM decreased 2.41 kg (10.6%, P < 0.001) in comparison with baseline. Twenty-four-hour urine creatinine excretion did not differ between study periods. No changes in intestinal absorption of fatty acids were seen, and no changes in EFAs measured in plasma phospholipids were observed. Only 1 of 8 patients, who did not receive parenteral lipids, had a Holman index above 0.2, indicative of EFA deficiency. All developed peripheral oedema. CONCLUSIONS: Combined high dose growth hormone and glutamine administered for 4 weeks, did not improve absorption of fatty acids or EFA status in short bowel patients. No changes in BW or composition were seen when comparing treatment to placebo periods. The increase in LBM measured by DEXA scan, comparing treatment and baseline periods, was not accompanied by an increase in the 24-h urinary creatinine excretion and is suspected to be associated with an accumulation in extracellular fluids. PMID- 11218240 TI - Effects of inhibition of PAF, ICAM-1 and PECAM-1 on gut barrier failure caused by intestinal ischemia and reperfusion. AB - BACKGROUND: The role of cell adhesion molecules and transmigration of PMNs through the endothelial barrier is probably essential in intestinal ischemia and reperfusion (I/R)-induced gut barrier dysfunction. Although cytokines are released in I/R, it is unclear whether cytokines directly increase permeability or if this phenomenon requires both expression of cell adhesion molecules and PMN adhesion-activation. Endothelial barrier dysfunction plays an important role in the pathogenesis of multiple organ dysfunction syndrome, inducing gut barrier failure, but the mechanisms are not fully understood. The purpose of this study was to evaluate the potential therapeutic value of inhibition of platelet activating factor (PAF), intercellular adhesion molecule-1 (ICAM-1), and platelet endothelial cell adhesion molecule-1 (PECAM-1) in gut barrier dysfunction induced by intestinal I/R. METHODS: A PAF antagonist (lexipafant, BB-882) and monoclonal antibodies against rat ICAM-1 (anti-ICAM-1-MAb) and PECAM-1 (anti-PECAM-1-MAb) were used in a model of gut barrier dysfunction caused by intestinal ischemia for 40 min and concomitant reperfusion for 12 h in the rat, and endothelial permeability, myeloperoxidase activity, interleukin-1beta and protease inhibitor levels were evaluated. RESULTS: The endothelial permeability and tissue leukocyte recruitment in the distal small intestine significantly increased in rats with I/R treated with saline. Proteolytic activity in plasma was evident by low levels of the three measured plasma protease inhibitors. These changes were, to different degrees, reduced by treatment with lexipafant, anti-ICAM-1-MAb, or anti PECAM-1-MAb. Alterations in systemic levels of interleukin-1beta paralleled the changes found in gut barrier permeability and leukocyte trapping. CONCLUSIONS: Our results suggest that treatment with the PAF inhibitor lexipafant and monoclonal antibodies against ICAM-1 or, seemingly most efficient, PECAM-1 reduces the severity of I/R-associated intestinal dysfunction, associated with a decrease in systemic concentrations of IL-1beta local leukocyte recruitment, and partly restoring plasma protease inhibitor levels. PMID- 11218241 TI - Mycophenolate mofetil reduces tissue damage and inflammation in an experimental model of colitis in rats. AB - BACKGROUND: Lymphocytes are widely believed to be responsible for persistent intestinal inflammation in inflammatory bowel diseases. Mycophenolate mofetil (MMF) is a potent immunosuppressant that inhibits lymphocyte proliferation and has been shown to be effective in preventing allograft rejection after organ transplantation. The purpose of this study was to assess the modulating effects of MMF on intestinal inflammation in an experimental model of colitis in rats. METHODS: Colitis was induced by rectal instillation of trinitrobenzenesulfonic acid (TNBS) in ethanol in male Sprague-Dawley rats. One group of rats (n = 10) was treated with MMF i.p. (25 mg/kg b.w.) daily for 1 week starting 24 h after induction of colitis. A second group of rats (n = 10) was treated with MMF at the same dose 2 days, I day and 1 h prior to induction of colitis. Control animals (n = 10) received vehicle only. After being killed, colonic tissue was macroscopically evaluated for necrosis and microscopically for ulcerations. Sections were stained and examined for the presence of granulocytes. RESULTS: Administration of MMF after induction of TNBS colitis reduced macroscopic injury by 62% compared to control animals (P = 0.01). Microscopic ulcerations were reduced by 64% compared to controls (P = 0.009). In addition, posttreatment significantly reduced the number of granulocytes. MMF pretreatment did not significantly prevent macroscopic or microscopic tissue damage, or change the number of granulocytes. CONCLUSION: Systemic administration of MMF significantly ameliorates tissue damage in a model of experimental colitis in rats suggesting that this compound may play an important role as an immunosuppressant in the therapy of inflammatory bowel diseases. PMID- 11218242 TI - Therapeutic drug monitoring of azathioprine and 6-mercaptopurine metabolites in Crohn disease. AB - BACKGROUND: 6-Mercaptopurine (6-MP) and its prodrug azathioprine (AZA) have proven efficacy in the treatment of Crohn disease (CD). The immunosuppressive properties of AZA/6-MP are mediated by the intracellular metabolism of 6-MP into its active metabolites, 6-thioguanine nucleotides (6TGN) and 6methylmercaptopurine (6-MMP). Preliminary studies have suggested that the red blood cell concentration of 6TGN (RBC 6TGN) is a potential guide to therapy. The aims of the study were to evaluate the RBC 6TGN concentrations in adult patients with CD under long-term AZA/6-MP therapy and to correlate it with response to treatment and haematological parameters. METHODS: Twenty-eight CD patients treated for at least 3 months with AZA/6-MP were prospectively studied. Patients were separated into three main groups: group 1 (n = 19), corresponding to quiescent CD receiving AZA (dose: 2.05 +/- 0.4 mg/kg/day for a mean of 28.6 +/- 25 months) or 6-MP (dose: 1.4 +/- 01 mg/kg/day for a mean of 7.5 +/- 3.5 months) alone; group 2 (n = 6), corresponding to quiescent CD treated by AZA (dose: 2.14 +/- 0.5 mg/kg/day for a mean of 29.5 +/- 22 months) with oral steroids; and group 3 (n = 3), corresponding to active CD on AZA (dose: 1.94 +/- 0.6 mg/kg/day for a mean of 31.3 +/- 35 months) as the only treatment. An assessment was also made by merging groups 1 and 2 forming a larger group of patients (n = 25) defined by clinical remission and groups 2 and 3 forming a larger group of patients (n = 9), non-complete responders with AZA/6-MP alone. Crohn disease index activity (CDAI), blood samples for full blood count and differential white cell count and measurement of RBC 6TGN and 6-MMP concentrations were evaluated at inclusion and at 6 months (n = 17). RBC 6TGN were measured using high performance liquid chromatography (HPLC) on heparinized blood. RESULTS: The baseline characteristics of the three groups of patients were similar. There was no significant difference among the three groups of patients regarding the dose and the duration of immunosuppressive treatment. There was no significant difference between groups according to various parameters tested. Particularly, the median RBC 6TGN concentration at inclusion was similar in the three groups of patients (166 (105 688), 183 (90-261) and 160 (52-194) pmol/8 x 10(8) RBC, respectively). The majority of patients had no detectable level of 6-MMP metabolite, except for 3 patients. There was also no difference between merging groups. Furthermore, there was no significant correlation between RBC 6TGN concentrations and the various biological parameters tested except for the mean erythrocyte volume. At 6 months, all patients of group 1 remained in remission and median RBC 6TGN concentration remained stable. No side effects were observed. CONCLUSIONS: There is, contrary to preliminary studies, a broad overlap in RBC 6TGN levels as well as for haematological parameters in patients in remission or not and responders or not to AZA/6-MP therapy. This suggests, beside a variability in the metabolism of these drugs, the existence of complex mechanisms of action. Nevertheless, beside the use of RBC 6TGN determination to confirm compliance to therapy, this dosage could be useful in non-responding patients, allowing, in absence of leukopenia, to increase the dose of AZA/6-MP safely. PMID- 11218243 TI - Validation of the inflammatory bowel disease questionnaire in Swedish patients with ulcerative colitis. AB - BACKGROUND: The Inflammatory Bowel Disease Questionnaire (IBDQ) is a disease specific health-related quality of life (HRQOL) questionnaire including four dimensions and a sum score. The aim of this study was to assess the internal and external validity, reliability, and sensitivity of a Swedish version of the IBDQ. METHODS: Three hundred consecutive patients with ulcerative colitis completed the IBDQ and three other health-related quality of life questionnaires (the Rating Form of IBD Patient Concerns (RFIPC), the Short Form-36 (SF-36) and the Psychological General Well-Being (PGWB) index). Disease activity was evaluated using a 1-week symptom diary, blood tests and rigid sigmoidoscopy. One hundred and fourteen patients filled in the questionnaire a second time, of whom 75 had been in stable remission for over 6 months and 39 had a significant clinical change in disease activity. RESULTS: Factor analysis of the 32 IBDQ items did not support the four dimensional scores. The dimensional scores had sufficient convergent validity, but low discriminative validity and homogeneity. The homogeneity was also low for the sum score. The inter-dimensional correlations were high. The concurrent validity was supported by correlations between the dimensional scores and other measures of disease activity and HRQOL. Patients in relapse scored significantly less on the sum score and the four dimensions compared to patients in remission. The test-retest correlations for the dimensional scores were 0.40-0.76. Patients with a change in disease activity during the 6-month follow-up period had a significant change in IBDQ scores not found in those who remained in remission. CONCLUSIONS: The Swedish version of the IBDQ had external validity and was shown to be a reliable and sensitive measure of HRQOL in ulcerative colitis, though there are some concerns regarding the internal validity. The use of a sum score was not supported and the questionnaire may benefit from a redivision of items into dimensions with better homogeneity and discriminative validity. PMID- 11218244 TI - Proliferation of alpha-smooth muscle actin-containing stromal cells (myofibroblasts) in the lamina propria subjacent to intraepithelial carcinoma of the esophagus. AB - BACKGROUND: The lamina propria of the digestive tract is the space containing vessels, myofibroblasts, and other interstitial components. The present study was undertaken to elucidate the relationships between the proliferation of myofibroblasts within this space and other histological features such as inflammatory cell infiltration and proliferation of blood vessels. METHODS: Thirty-eight cases in total-comprising 19 cases of early and 19 cases of advanced esophageal squamous cell carcinoma with intraepithelial extension (the former including 10 lesions of carcinoma in situ and 15 lesions of carcinoma with invasion only into the lamina propria)-were examined using H&E staining, Azan Mallory staining, and immunostaining for the characterization of mesenchymal cells in the lamina propria against alpha-smooth muscle actin (alphaSMA), desmin, vimentin, factor VIII, collagen type IV, laminin, or inflammatory cells (L26, UCHL1, Kp1, and c-kit). The proliferative potential of myofibroblasts was evaluated by measuring the total length of the bundles of myofibroblasts per case. RESULTS: Proliferation of alphaSMA-containing stromal cells: i) occurred in the lamina propria subjacent either to intraepithelial carcinomas (64%) or to the intraepithelial extension of carcinoma tissue (47%), and ii) showed a significant correlation with both the degree of mononuclear cell infiltration (mostly UCHL1 positive T cells) and the total length of the carcinoma tissue in each case. CONCLUSIONS: Proliferation of alphaSMA-containing stromal cells in the lamina propria may be involved in altering the endoscopic features of the esophagus in cases with intraepithelial carcinoma or an intraepithelial extension of carcinoma tissue. PMID- 11218245 TI - Small intestinal bacterial overgrowth versus antimicrobial capacity in patients with spontaneous bacterial peritonitis. AB - BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a serious infection in cirrhotic patients with ascites. Both defects in the host defense mechanisms and the enhancement of the offensive factor (small intestinal bacterial overgrowth (SIBO)) may contribute to the development of SBP. Therefore, the aim of this study was to evaluate the role of SIBO versus various antimicrobial capacities in the pathogenesis of SBP in cirrhotic patients. METHODS: Forty-five cirrhotic patients were enrolled in this study. Bacterial overgrowth was evaluated by breath hydrogen test (BH2T). The hepatic reticuloendothelial system phagocytic index (HRESPI) was measured by intravenously injected colloid suspensions. RESULTS: The Child-Pugh scores in the SBP group were higher than in the non-SBP group (10.5 +/- 2.0 versus 8.0 +/- 1.8, P < 0.01). The ascitic protein concentration was significantly lower in the SBP group than in the non-SBP group (897 +/- 425 mg/l versus 1,325 +/- 453 mg/l, P < 0.01). Furthermore, the serum C3 concentration was lower in the SBP group than in the non-SBP group (43.1 +/- 13.6 ng/dl versus 73.2 +/- 26.4 ng/dl, P < 0.01). The serum C4 concentration was also lower in the SBP group than in the non-SBP group (12.4 +/- 4.0 ng/dl versus 16.9 +/- 6.6 ng/dl, P < 0.05). The incidence of SIBO was higher in the SBP group than in the non-SBP group (68.2% versus 17.4%, P < 0.01). HRESPI values were significantly higher in the two groups of cirrhotic patients than in the normal reference. However, there were no statistical differences in HRESPI between the two groups (8.4 +/- 2.8 min in the SBP group versus 7.9 +/- 2.8 min in the non SBP group). CONCLUSIONS: The results of this study showed that the hepatic reticuloendothelial function is impaired in cirrhotic patients, but the degree of impairment does not differ between patients with and without previous history of SBP. Lower ascitic total protein, lower serum C3 and C4 concentrations, and presence of SIBO are all risk factors for SBP. Based on the results of our study, defects in the host defense mechanisms and the enhancement of the offensive factor (SIBO) may act in concert for the development of SBP. PMID- 11218247 TI - [What is your diagnosis? Lung metastases of hypopharyngeal carcinoma]. PMID- 11218246 TI - Sustained virological response in chronic hepatitis C patients after a 6- and a 36-month interferon-alpha2b treatment schedule: a multicenter, randomized, controlled study. AB - BACKGROUND: In patients with chronic hepatitis C (HCV) Interferon-alpha (IFN) treatment for 12-18 months is more effective than 6 months in inducing a sustained virological response. METHODS: In a multicenter, randomized, controlled trial, 88 patients with chronic HCV were enrolled (47 treated with IFN-alpha2b and 41 constituted an untreated control group). Treatment consisted of 5 million units (MU) IFN thrice a week (tiw) for 8 weeks and subsequently 2.5 MU IFN tiw for 16 weeks ('standard treatment'). After week 24 ('long-term treatment'), in virological non-responders treatment was continued using 5 MU IFN tiw for up to week 156, whereas in virological responders IFN was discontinued. In case of a virological relapse, treatment with 5 MU IFN tiw was restarted and continued up to week 156. RESULTS: Sustained virological response rate was 6/47 (13%) after standard treatment and increased to 19/47 (40%) after long-term treatment (McNemar paired test; P = 0.002). Of the 18 patients with a breakthrough or relapse during or after standard treatment, 14 (78%) became sustained virological responders upon long-term treatment. Of the 4 patients who did not have a sustained virological response after long-term treatment, 3 did not receive complete treatment due to side effects and/or non-compliance. In patients who failed to respond to standard treatment, no virological response was observed during long-term treatment. In the control group, no spontaneous clearance of HCV was observed. CONCLUSIONS: Long-term IFN (re)treatment enhanced the virological sustained response rate significantly and was particularly effective in patients with a breakthrough or relapse following standard treatment. PMID- 11218248 TI - Child abuse and neglect: the dental assistant's role in prevention. AB - Child abuse and neglect are growing at ever increasing rates in the U.S. It is not only within the purview of dental practice to identify and report suspected cases, it is also required by state law. An appropriate child abuse and neglect protocol in your dental practice is the best defense children may have to prevent these problems. Talk about abuse and neglect at your staff meetings. Be aware of the warning signs, know what to consider when you see an injury, and know how to make a report. When you see a child that may be a victim, remember that everyone else in the dental office has seen the same child and may have useful information. Talk privately among yourselves about what you see and hear. Encourage your dentist to fulfill his or her legal obligation to report suspected cases, but understand that anyone can make a report, whether specified as a mandated reporter or not. Remember that breaking the cycle of child abuse and neglect not only can make your patient happier and healthier, it may save a child's life. PMID- 11218249 TI - Arsenic and heavy metals in leachate from a real landfill and a laboratory landfill. AB - A preliminary study, based particularly on Arsenic and some heavy metals determination (Cd, Cr, Hg and Pb) in three leachate tipologies produced from municipal waste landfill plant, lab-scale aerobic landfill, lab-scale anerobic landfill was undertaken. Leachate was collected and analysed monthly; samples were homogenized and then, all heavy metals were determined after mineralization, except for Hg, determined before mineralization, due to his high volatility. In all samples pH was measured. In general we can say that low concentrations of the elements analyzed were found in all kinds of landfills considered; in particular, in the lab-scale anaerobic reactors, where low pH values have been found, we have a more considerable mobilization of As and the others heavy metals, moreover due to the behaviour of these elements. PMID- 11218250 TI - Assessment of the metals contamination of the low Sebou sediments (Morocco). AB - The heavy metals contamination of the lower Sebou sediments was studied to determine the average degree of contamination and to assess the extent of anthropogenic contamination. The spatial and temporal distribution of these metals and the results of the contamination indices showed very serious metallic contamination principally of Cr, Pb and Hg. However accurate analysis of the situation in the river mouth was complicated by the fact that the metals could be moved by the tides and currents. PMID- 11218251 TI - Determination of metals in thoracic fraction of ambient air particulate matter. AB - The present work deals with the optimization and validation of a method for the quantitative simultaneous ICP determination of metals in ambient air particulate matter. The attention has been focused on the thoracic fraction (PM10) and twelve different metals were chosen on the basis of their toxicity and of their possible use as chemical tracers. The microwave acidic digestion of the samples has been performed in the presence of different reagents and under different conditions and particular attention has been paid to the optimization of the whole analytical procedure and to the evaluation of accuracy and precision related to the single operative steps. The interferences due to the reagents and to the sampling supports have also been evaluated. In addition, the analytical procedure has been checked by examining the equivalence of results related to parallel sampled filters pairs. PMID- 11218252 TI - Changes in copper, lead and zinc concentrations in plants from paper mill sludge treated soils. AB - Effects of paper mill sludge addition on the availability of metals were studied on different soils both laboratory and naturally polluted; copper, lead and zinc concentrations were determined in Hordeum Distichum plants grown on the untreated and on sludge-treated soils. In some case a decrease of metal concentration is observed on sludge-treated soils; these results are consistent with the reduction of metal mobile forms in the soil, before plant growth. The decrease of metal availability in sludge-treated soils may be related with the pH value of the soil after sludge addition. PMID- 11218253 TI - Civilian and military uses of depleted uranium: environmental and health problems. AB - Depleted uranium is a by-product of the process of enrichment of natural uranium and is classified as a toxic and radioactive waste; it has a very high density (approximately 19 g cm-3), a remarkable ductility and a cost low enough to be attractive for some particular technical applications. Civilian uses are essentially related to its high density, but the prevailing use is however military (production of projectiles). From the radioactive point of view, the exposure to depleted uranium can result from both external irradiation as well as internal contamination. The associated risks are however mainly of chemical toxicological kind and the target organ is the kidney. In the present note the recent military uses and the possible effects of its environmental diffusion are discussed. PMID- 11218254 TI - Assessment of ground water quality in a fractured aquifer under continue wastewater injection. AB - Experimental studies have been carried out in a fractured coastal aquifer of the Salento Region (Nardo (Le), Italy), subject since 1991 to injection of 12,000 m3/d of treated municipal wastewater in a natural sink. The analytical parameters of ground water sampled in monitoring wells, have been compared before and after the injection started. The mound of water table (1.5 m), the reduction of seawater extent of 2 km and the spreading of pollutants injected were evaluated by means of mathematical model results. After ten years operation, the volume of the available resource for agricultural and drinking use has been increased, without notable decrease of the preexistent ground water quality. Moreover for preserving such resource from pollution, the mathematical model allowed the standards of wastewater quality for recharge to be identified. Around the sink, a restricted area was also defined with prohibition of withdrawals, to avoid infection and other risks on human health. PMID- 11218255 TI - Soil decontamination at the Montevecchio-Levante mine site with experimental washing and leaching techniques. AB - The soils in the neighbourhood of the Rio Montevecchio-Sitzerri, a stream that flows in the valley below the tailings pond of the Montevecchio-Levante mineral processing plant (SW Sardinia, Italy) are severely contaminated by heavy metals, to the extent that traditional land uses are compromised. Consequently urgent measures are needed both to abate the pollution at source and rehabilitate the contaminated land. This paper is concerned with the problem of soil decontamination using washing and leaching techniques. Laboratory experiments have been conducted in mechanically agitated reactors, using citric acid and acetic acid solutions and brine of hydrochloric acid and calcium chloride. The influence of both reagent concentration and solid-to-liquid ratio has been assessed, and in the most significant cases, the attack kinetics has been determined. The tests showed the brine to be the most effective for removing metals from the soils. Based on the findings of the investigations, the possibility of decontamination by heap leaching has been simulated in the laboratory using the column technique. PMID- 11218256 TI - The impact of lead pollution on the environment of Rabat-Sale' (Morocco). AB - There are numerous possible vectors of industrial lead poisoning in unprotected work environments and the areas surrounding industrial sites. In the Rabat-Sale region, ceramics is the industry which uses most lead. Galena (PbS) is used in the fabrication of some types of pottery, and other lead-based compounds are used as glaze. A second source of lead pollution is the production of some fuels, in which lead is used as an anti detonator. In order to evaluate the impact of lead contamination on the environment, our investigation is focused on the lead concentration in the atmosphere, soil and vegetation at five stations in the Rabat-Sale region. We found concentrations of lead higher than those published for any other country in the atmosphere and vegetation near the ceramics factories of Rabat-Sale. These concentrations decreased significantly as we moved away from urban areas. PMID- 11218257 TI - Cadmium chronic administration to lactating ewes: reproductive performance, cadmium tissue accumulation and placental transfer. AB - 20 lactating ewes were allotted to two groups: 10 subjects received orally 100 mg/day of CdCl2 for 108 consecutive days, and the remaining 10 acted as control. Reproductive performance in ewes and cadmium tissue accumulation, both in ewes and their lambs, were investigated. The results showed that in ewes: 1) the regular cadmium intestinal intake negatively influences all reproductive parameters; 2) cadmium is particularly accumulated in kidney and liver, but also in mammary gland, although at a distinctly lower level; 3) chronic administration does not increase cadmium placental transfer in lactating pregnant subjects. PMID- 11218258 TI - Genotoxic effects of cadmium chloride on human amniotic fluid cells cultured in vitro. AB - In this study we report the results of cytogenetic tests, namely a search for chromosome aberrations (CA) and sister chromatid exchanges (SCEs), performed on human amniotic fluid cells cultured and treated with Cadmium chloride. The cells from primary cultures were exposed to CdCl2 at 1 microM and 10 microM for 24 h. At the higher dose, no metaphases were scored and at the lower dose (1 microM) no effects were evident on cell proliferation, and no chromosome aberrations were found. In the subsequent experiments we used cells from subcultures exposed to 1 microM and 5 microM CdCl2. At the 5 microM dose was evident the induction of chromatid breaks, while the frequency of sister chromatid exchanges shows a small increase, not statistically significant at the dose of 1 microM. In this study we positively demonstrated that amniotic fluid cells grown in vitro are reliable for testing various mutagenic or teratogenic substances. With regard to cadmium treatment results, it is evident a clastogenic effect of cadmium chloride but not a significant induction of SCEs. PMID- 11218259 TI - Model for the study of the impact of atmospheric heavy metals on soil microbial biomass. AB - In the Castelporziano (Rome) protected area the inputs of atmospheric heavy metals on the soil-plant system were evaluated by the analysis of stem-flowing water from Quercus ilex L. The heavy metals detected in the soil under the canopies exhibited higher concentrations near to the tree trunks, highlighting the tree's capacity to concentrate such polluting substances. Microbial biomass, its specific respiration and the biomass calculated as a percentage of total soil organic matter, were utilised as indicators of the state of the soil and consequently also its quality with respect to heavy metal contamination. PMID- 11218260 TI - Methodological approach for an integrated environmental monitoring system relative to heavy metals from an incineration plant. AB - The use of an Integrated Environmental Monitoring System is an innovative and very important approach for the determination of environmental impacts due to a contamination source. In the present work, the methodological approach is described and applied to the case study of a MSW incineration plant. Heavy metals were chosen as Environmental Indicators. Gaseous emissions were measured and correlated to wet and dry depositions, soil and vegetation samples. Results show a good correlation between stack emissions and atmospheric depositions; less with soil and vegetation, but these results are important in order to design a standard procedure for an Integrated Monitoring System. PMID- 11218261 TI - Effects of fire on the state of several elements in some soils of Sardinia. AB - In order to individuate the modifications induced in the soil by fires relatively to the mobility of metals and rare earth three soils of Sardinia which differ in their mineralogical and physico-chemical characteristics were sampled. The analytical results obtained on the samples drawn at different depths (0-5 and 10 30 cm) three months after a fire and on the tests indicate that only the surface layer underwent significant modifications. The dynamics of metals and the distribution of the rare earths were found to depend, besides the amount and quality of the burned material, on the different behaviour of elements towards leaching. The diffractometric analysis showed that the soil surface layer of all the samples did not exceed 400 degrees C. PMID- 11218262 TI - Heavy metals contents in organic amendments based on beached Posidonia oceanica. PMID- 11218263 TI - Propofol sedation in general dental practice: the first 100 patients. AB - Experience is presented of the treatment of 100 patients for routine dentistry in general dental practice under propofol (Diprivan) sedation, delivered by continuous infusion. The infusion rates were set manually according to patients' responses. There were no differences in dental treatment or propofol requirements according to gender. Propofol requirements in some cases exceeded the upper limit of the recommended dose ranges and reasons why this may have occurred are discussed. A most useful feature of propofol sedation was the associated rapid recovery, with no patients needing to remain in the surgery for the purposes of recovery. The technique met with patients' approval, as all responses returned indicated a willingness to undergo the same type of sedation in future. Propofol sedation is not appropriate for the single operator/sedationist. PMID- 11218264 TI - Management of molar teeth with periodontal disease. AB - Over the years patients' attitudes towards maintaining a functional and aesthetic masticatory apparatus have improved, and their expectations of delivery of care by the dental professional have risen. With the advance of new techniques and materials, the periodontist can now offer an ever-expanding range of treatments in the management of molar teeth with periodontal disease. This paper considers such treatment in relation to the levels of disease present and within the overall context of adult restorative dental healthcare. PMID- 11218265 TI - Implant complications and failures: the single-tooth restoration. AB - The single-tooth implant restoration appears to be an ideal method of replacing missing natural teeth in a healthy dentition. Most follow-up studies report a high success rate. The restoration is seen by many clinicians as a relatively straightforward technique easily adapted to general dental practice and popular with patients, although it is not without complications. The purpose of this paper is to look at common problems following the placement of root-formed endosseous dental implants. A number of implant systems are reviewed and the results of the authors' clinical experiences reported. PMID- 11218266 TI - Orofacial disease: update for the dental clinical team: 11. Cervical lymphadenopathy. AB - By far the most common causes of lumps in the neck are swollen lymph nodes. The most common cause of cervical lymphadenopathy is infection in the area of drainage (virtually anywhere in the head and neck). Most frequent of all is an enlarged jugulodigastric (tonsillar) lymph node, inflamed secondary to a viral upper respiratory tract infection. Enlarged cervical lymph nodes may also be a manifestation of systemic infection (e.g. HIV/AIDS), or related to malignant disease in the drainage area (e.g. carcinoma) or elsewhere (e.g. leukaemia or lymphoma). These and less common causes are discussed in this, the last article in this series. PMID- 11218267 TI - Strategies for dental clinic infection control. AB - The application of proper infection control procedures helps to protect practitioners, patients and the community. The goal is to minimize the spread of potentially pathogenic micro-organisms and to remove and/or kill organisms that have contaminated objects and surfaces. Dental practitioners are aided in this process by the generation of rules, guidelines and recommendations by regulatory agencies and professional organizations. Ideally, each office/clinic would generate and maintain a written set of infection control procedures. PMID- 11218268 TI - A case report of pre-eruptive coronal resorption in a mandibular canine. PMID- 11218269 TI - Orofacial disease: update for the clinical team: 9. Orofacial pain. PMID- 11218270 TI - A forgotten entity: 'broken needle while inferior dental block'. PMID- 11218271 TI - 'Sweetie-free' policy. PMID- 11218272 TI - Ethics in aesthetics? PMID- 11218273 TI - Parkinson's disease and oral care. AB - Parkinson's disease is a relatively common, progressive, neurological disorder. Its key features of resting tremor, bradykinesia, akinesia, restricted mobility and postural instability militate against independence for daily living, mobility, good nutrition and oral health. The successful management of the disease requires a multi-disciplinary approach in which the dietician, speech therapist, nurse and dental staff are pivotal members of the care team. PMID- 11218274 TI - Economic evaluation and dentistry. AB - This article is a brief guide to economic evaluation and dentistry. It outlines the most common methods such as cost-effectiveness analysis and cost-benefit analysis; discusses how and when they should be used; gives some dental examples; and outlines important issues that need to be borne in mind when interpreting them. It also corrects one or two common misunderstandings about economic evaluation. PMID- 11218275 TI - Diver's mouth syndrome: a field study. AB - Reports of clinical presentations of diver's mouth syndrome and prevalence of at least one of its symptoms in many successive Joint Service (JS) diving expeditions prompted the author (who is an advanced diving instructor and an Armed Forces dental surgeon and has been present on, or organized, at least six JS diving expeditions in regions from cold temperate to tropical) to construct customized diving mouthpieces and investigate their effectiveness during intensive use in the field. PMID- 11218276 TI - A comparison of written and multimedia material for informing patients about dental implants. AB - A study was undertaken to compare the effectiveness of an information leaflet with a multimedia program in informing potential implant patients attending a dental hospital. The results show that both methods of presenting information are effective in informing patients; however, where the information to be presented is visual in nature, a multimedia presentation can have a more positive short term effect than an equivalent leaflet. PMID- 11218278 TI - An overview of the prevention of oral cancer and diagnostic markers of malignant change: 1. Prevention. AB - The incidence of oral cancer appears to be on the increase, with patients presenting at an earlier age. An overview of the prevention of this important condition is given in this article, and diagnostic markers will be discussed in a later presentation. Greater awareness of the aetiological agents involved in the development of oral cancer, and their avoidance, should help reduce the number of cases. General dental practitioners have an important role to play in advising patients on healthier lifestyles (primary prevention), the detection of potentially malignant disease before it becomes malignant (secondary prevention) and screening for field changes in patients with a history of oral cancer. The role of chemoprevention (defined here as tertiary prevention) is also considered. PMID- 11218277 TI - Dentine bonding systems: 1. Mode of action. AB - The achievement of a reliable bond to dentine has been more difficult than bonding to enamel, due principally to the anatomy of the dentine substrate. The mechanisms of bonding are now much better understood than a decade ago and clinically-viable bond strengths to dentine are now achieved with many dentine bonding systems. PMID- 11218279 TI - Thoughts on the atraumatic restorative treatment (ART) technique. PMID- 11218280 TI - Antimycotic agents in oral candidosis: an overview: 1. Clinical variants. AB - The advent of the human immunodeficiency virus and the increasing prevalence of immunocompromised individuals in the community have resulted in a resurgence of opportunistic infections, including oral candidoses. Despite the availability of a number of effective antimycotics for the management of oral candidoses, therapeutic failure is not uncommon. Further, the presence of many clinical variants of oral candidosis, both new and old, may confound the unwary clinician and complicate its management. These problems have been partly circumvented by the introduction of the triazole group of antimycotics, which initially appeared to be highly effective. However, an alarming increase in organisms resistant to triazoles has been reported recently. In this paper we provide an overview of clinical variants of oral candidosis. A second paper will discuss recent advances in the usage of antimycotics in the management of this condition. PMID- 11218281 TI - The atraumatic restorative treatment (ART) technique: does it have a place in everyday practice? AB - The ART technique was introduced in the early 1990s. It involves the removal of carious tooth tissue with hand instruments followed by restoration with an adhesive material (glass-ionomer cement). Local anaesthetic is not always required for treatment and the technique has helped to bridge the gap in the provision of treatment to rural communities, senior citizens and dental phobic patients. This article looks at the development of the technique, its performance and potential areas of application. PMID- 11218282 TI - Dentine bonding systems: 2. Clinical uses. AB - As the reliability of dentine bonding agents has improved, the clinical uses of these systems has increased and now include the bonding of directly and indirectly constructed restorations, amalgam bonding and treatment of dentinal sensitivity. Areas of potential use which require further evaluation include pulp capping and the attachment of fractured tooth fragments. PMID- 11218283 TI - Malignant lymphoma of the maxillary sinus masquerading as an odontogenic infection: report of a case. AB - The dental surgeon can play an important role in the early referral of malignancy of the maxillary sinus, and should be familiar with the signs and symptoms of disease of the paranasal sinuses. Here we report a case of a 71-year-old male patient diagnosed with high-grade B-cell lymphoma of the maxillary sinus that was initially thought to be an odontogenic infection. We discuss the signs and symptoms of lymphomas and malignancy of the maxillary sinus. PMID- 11218284 TI - Modified apically repositioned flap in the treatment of unerupted maxillary central incisors. AB - The successful management of labially unerupted maxillary central incisors requires a coordinated surgical, orthodontic and general practitioner approach. The key to achieving maximal eruption of these teeth is their surgical exposure, central to which is the philosophy that the surgeon must provide a functional width of attached gingiva on the labial surface. This case describes the incorporation of palatal mucosa into an apically repositioned flap, resulting in the successful establishment of an attached gingival margin, where routine flap design would have seriously compromised the eventual outcome. PMID- 11218285 TI - Inhalation sedation with nitrous oxide: a review. AB - The General Dental Council guidelines regarding the use of general anaesthesia in general practice have changed; inhalation sedation with nitrous oxide has been shown as a safe alternative to general anaesthesia for many patients and is a technique particularly suited to the practice environment. PMID- 11218286 TI - An overview of the prevention of oral cancer and diagnostic markers of malignant change: 2. Markers of value in tumour diagnosis. AB - Earlier diagnosis of oral cancer should lead to an improvement in prognosis. This, the second part of a two-part overview, is concerned with the various cellular markers available for diagnosis of oral cancer. Traditionally diagnosis has relied upon the histomorphological interpretation of a tissue section following biopsy. The application of advances in various laboratory techniques for the identification of different cellular markers is briefly reviewed. In addition, although it is currently only a research tool, the potential role of oral exfoliative cytology in screening is considered. PMID- 11218287 TI - Adhesive solutions: report of a case using multiple adhesive techniques in the management of enamel hypoplasia. PMID- 11218289 TI - The anatomy of a firing. When you finally act, it's often later than you think. PMID- 11218288 TI - A fresh look at effective telephone screening. Part 1: General guidelines. PMID- 11218290 TI - Impact of fluoride on dental health. PMID- 11218291 TI - Commit to being the best. PMID- 11218292 TI - Billing a patient's medical insurance. PMID- 11218293 TI - E-mail. 20 reasons why you should have it in your dental office. PMID- 11218294 TI - [Unexplained weight loss in the elderly: role of gastric fibroscopy, study of a cohort of 77 patients with a 13-month follow-up]. AB - PURPOSE: In case of unexplained weight loss, chest X-ray, abdominal ultrasonography and gastroscopy are usually recommended. However, gastroscopy is not usually performed in elderly patients. METHODS: We evaluated 77 patients (mean age: 80 +/- 8 years) hospitalized in our geriatric unit between January 1995 and May 1997 for unexplained weight loss. All patients underwent chest X ray, abdominal ultrasonography and gastroscopy. RESULTS: These investigations led to diagnosis in respectively 17, 15 and 46 patients. The etiology of weight loss was unique in 47 patients, while in 30 other patients at least two or three causes could be described. Gastroscopy appeared to be the most useful test, as it allowed description of eight cases of cancer, 29 cases of peptic ulcer, two cases of candidosis, and one case of actinomycosis in patients who did not present any clinical sign. CONCLUSION: Sixty-five patients were followed-up for a mean period of 13 +/- 21 month; 33 patients died. The condition of 23 patients improved either slightly or definitely. Simple investigations led to diagnosis in 95% of the cases. However, 42% of the patients died within 3 months. Gastroscopy appears to be the most valuable test, leading to diagnosis in more than half of the cases. With adapted treatment, the condition of 75% of the patients with gastro intestinal lesions improved. PMID- 11218295 TI - [Small intestine bacterial overgrowth: six case reports and literature review]. AB - INTRODUCTION: Small intestinal bacterial overgrowth syndrome (SIBOS) has various clinical and biological presentations. Six observations are described in this review which is aimed at reporting recent data on SIBOS and proposing diagnosis and therapeutic attitudes. CURRENT KNOWLEDGE AND KEY POINTS: Chronic diarrhea, malabsorption syndrome and exsudative enteropathy are the main criteria of diagnosis. Breath hydrogen testing is commonly performed to confirm diagnosis, with a 78% sensitivity and a 89% specificity. The aim of therapy is reparation of malabsorption consequences, reduction of intestinal bacterial overgrowth, and surgical correction of intestinal stasis. In the absence of consensus, norfloxacin or amoxicillin-clavulinic acid (administered for a mean of 7 to 15 days) seem the more appropriate antibiotics. When possible, surgery represents the primary treatment of SIBOS recurrences. FUTURE PROSPECTS AND PROJECTS: Diagnosis of small intestinal bacterial overgrowth syndrome must be evoked on the basis of either surgical or medical context, i.e., the existence of chronic diarrhea, malabsorption syndrome (complete or not), and exsudative enteropathy. This review reports essential factors for diagnosis and treatment. PMID- 11218296 TI - [Risk factors for irreversible cerebral ischemia complications from Horton's disease: prospective study of 178 patients]. AB - PURPOSE: To search for risk factors of developing irreversible cranial ischemic complications (ICIC) in patients with giant cell arteritis (GCA) and to explore whether two subsets of patients (high risk and low risk of developing ICIC) can be defined. METHODS: One-hundred seventy-eight consecutive patients with temporal arteritis (149 biopsy-proven) were diagnosed and followed up in a department of Internal Medicine between 1976 and 1999. The patients were separated into two groups, according to the presence or absence of ICIC, with comparison of 17 clinical and biological parameters prospectively recorded for each patient using a pre-established comprehensive questionnaire. RESULTS: ICIC occurred in 25 patients (14%), with amaurosis in 22 cases. Suggestive symptoms and/or signs of temporal arteritis were present in 92% of the patients, lasting 50 days (median) before the onset of ICIC. Forty-three patients (24%) complained of transient visual ischemic symptoms (TVIS), which preceded acute blindness in 11 cases. A multivariate logistic regression, from which 28 cases with upper limb artery involvement were excluded for technical reasons (no CCII in any case, thus predicting perfectly the lack of ischemic risk, P = 0.02), indicated that the only independent variables associated with the ischemic risk were: a history of TVIS (P = 0.05), the lack of signs of polymyalgia rheumatica (PMR; P = 0.02), lower blood levels of fibrinogen (P = 0.024) and higher mean blood platelets levels (P = 0.006). However, these five variables predicted only 30% of the variability of the model. Sensitivity, specificity, positive and negative predictive values of the model reached respectively 36, 96, 64 and 88%. Overall, 86% of the cases were correctly classified with respect to the ischemic risk. CONCLUSION: The rate of ICIC should be reduced by an earlier recognition of the usual signs of temporal arteritis. Several independent risk factors of ICIC have been identified. However, the logistic model failed to predict accurately the ischemic risk in 14% of the cases, indicating that as yet unrecognised factors probably exist that play a role in the occurrence of ICIC. Nevertheless, regarding the strong association between platelet levels and ICIC, patients with thrombocytosis should receive initially both corticosteroids and antiplatelet agents. PMID- 11218297 TI - [Current antiretroviral therapy]. AB - INTRODUCTION: Advances in HIV/AIDS therapy have been rapid and profound. CURRENT KNOWLEDGE AND KEY POINTS: In developed countries the epidemic infection has stabilized and there are dramatic decreases in morbidity and mortality resulting from the use of intensive but expensive therapies. HIV patients who have detectable viral loads and/or evidence of immunologic dysfunction should be treated with a potent combination antiretroviral regimen. Currently, this consists of two nucleoside reverse transcriptase inhibitors with at least one protease inhibitor, or a non-nucleoside reverse transcriptase inhibitor, or another combination with adequate potency. Current therapies do have limitations, including side effects, cross-resistance, adherence challenges, and drug interactions. FUTURE PROSPECTS AND PROJECTS: Drug resistance is a major factor contributing to the failure of antiretroviral therapy: the ability to predict clinical response to therapy on the basis of genotype and/or phenotype depends on knowledge of appropriate data for defining drug resistance. Moreover, careful selection and monitoring of combination drug therapy along with individualized rather than standard dosage regimens may minimize the pharmacological problems and help ensure optimum antiviral activity. Further developments include new drugs, vaccine, cytokine-, and gene therapy-based treatment strategies. PMID- 11218298 TI - [Thalidomide: the revival]. PMID- 11218299 TI - [What is current opinion of antiviral therapy for the flu in 2001?]. AB - INTRODUCTION: The availability of new neuraminidase inhibitors which interact on the influenza A and B viruses could be the start of a new approach to flu treatment. Until now, vaccination has been the principal medical treatment, except in the case of a pandemic caused by antigenic shifts. In this article the authors will answer the following questions: Potentially, is there room for antiviral drugs and why? Are these drugs efficient and according to which criteria? Who are they for? And what indications must be followed? Are they well tolerated? Do they induce any viral resistance? M2 protein inhibitors (i.e., amantadine and rimantadine) are compared with neuraminidase inhibitors (i.e., zanamivir and oseltamivir). CURRENT KNOWLEDGE AND KEY POINTS: Neuraminidase inhibitors prescribed during the first 48 h have a medical curative effectiveness on non-complicated forms carried by healthy patients--symptoms last no longer than 1 to 3 days and their severity is reduced. This efficiency could potentially concern unexpected complications due to the diminution of antibiotics absorption. The inhibitors seem to induce little resistance and are responsive to influenza B as opposed to the M2 protein inhibitors. They seem to be well-tolerated by patients and they are also efficient when it comes to prophylaxis measures. FUTURE PROSPECTS AND PROJECTS: It is assumed that these treatments are used in a curative and preventive manner in order to give them their full strategic importance (their use is currently forbidden in France). This importance will require that physicians and the population be well aware of the epidemic and that responsive physicians who know the medical indications quickly implement the treatment. It is necessary to carry out surveys with those at risk who are seriously ill with the flu in order to measure ratios such as cost efficiency. The use of these treatments will have to be evaluated, bearing special attention on the risks of the emergence of resistant viruses and on the impact on vaccination. PMID- 11218300 TI - [Testicular seminoma and multifocal aseptic osteonecrosis following chemotherapy]. AB - INTRODUCTION: Multifocal osteonecrosis has a wide variety of etiologies, but in the cancer patient several risk factors could have a synergic effect (chemotherapy, radiotherapy, corticosteroid, metabolism disorder). EXEGESIS: A patient with testicular seminoma receiving cisplatin-based chemotherapy and short term corticosteroid developed multifocal osteonecrosis. Early diagnosis of osteonecrosis is important to prevent orthopedic complications. CONCLUSION: Cisplatin could represent one of the possible etiologies of multifocal osteonecrosis. Magnetic resonance imaging has a high sensitivity and specificity in the diagnosis of osteonecrosis and should be used when this condition is suspected. PMID- 11218301 TI - [Dilated cardiomyopathy and panuveitis as presenting symptoms of Lyme disease. General review of one case]. AB - INTRODUCTION: The clinical expression of Lyme disease is highly variable. If a patient presents clinical findings consistent with a systemic Lyme borreliosis, this disease must be considered in an endemic area because of its favorable outcome with adequate treatment. EXEGESIS: The authors report and discuss the case of a patient with an unusual history of dilated cardiomyopathy and supraventricular fibrillation followed by bilateral panuveitis. Enzyme-linked immunosorbent assay and Western blot were positive for Borrelia burgdorferi antigens. The diagnosis of Lyme disease was made after other infectious, inflammatory and autoimmune disorders were excluded by clinical, instrumental and biological investigations. The treatment by ceftriaxone and amoxicillin resolved the ophthalmologic manifestations and improved the cardiac condition. CONCLUSION: This report underlines the possibility of an unusual presentation of Lyme disease. Ophthalmologic and cardiac involvement should be known by clinicians. PMID- 11218302 TI - [McDuffie hypocomplementemic urticarial vasculitis. Two cases and review of the literature]. AB - INTRODUCTION: Hypocomplementemic urticarial vasculitis (HUV) described by McDuffie is a rare entity recently individualized among vasculitis. We report two new cases. EXEGESIS: Case 1: a 41-year-old woman presented in 1994 with inflammatory polyarthralgia, diffuse urticaria, fever, and weight loss. Biology showed proteinuria, positive rheumatoid factor with hypocomplementemia and negative immunological tests. Skin and renal biopsies showed leukocytoclastic vasculitis and extramembranous glomerulopathy, respectively. Outcome within steroid therapy was marked by alternating clinical improvement and relapses. Case 2: a 39-year-old woman presented in 1994 with inflammatory polyarthritis, diffuse urticaria, Raynaud phenomenon, cough and dyspnea. Chest x-rays and CT scan showed interstitial fibrosis and echocardiography revealed pericarditis. Biology showed positive rheumatoid factor with hypocomplementemia and negative antinuclear antibodies. Skin biopsy showed leukocytoclastic vasculitis. Corticosteroids and cyclophosphamide improved the patient's condition. McDuffie HUV is a disease with varied systemic manifestations. Its existence is still contested by some authors. Treatment is still empirical and depends on the clinical features. It is based primarily on corticosteroids. CONCLUSION: McDuffie HUV is a defensible entity among urticarial vasculitis because of its particular clinical and biological features. PMID- 11218303 TI - [Primary Neisseria meningitidis arthritis of the knee without meningitis: contribution of synovial fluid culture in blood-culture vial]. AB - INTRODUCTION: Primary meningococcal arthritis is a rare form of meningococcal disease. It occurs as an isolated acute purulent arthritis without meningitis, and presence of Neisseria meningitidis in articular fluid. We report a new case of typical primary meningococcal arthritis. EXEGESIS: A previously healthy 23 year-old female patient was admitted for purpuric lesions of the legs. At admission, conscience was normal and symptoms of meningitis were absent. During the 2nd day of hospitalisation, a warm and painful effusion in the right knee appeared. Aspiration from the right knee yielded a purulent fluid. N. meningitidis was isolated from a blood-culture vial inoculated with the synovial fluid, while blood cultures remained sterile. Anti-biotherapy was initiated as soon as microbiological diagnosis was established. The patient was symptom-free 1 month later. CONCLUSION: We emphasize the fact that agar cultures of the synovial fluid remained sterile, while N. meningitidis grew in a blood-culture vial. We suggest that diagnosis of primary meningococcal arthritis may be underestimated when inappropriate culture media are used. PMID- 11218304 TI - [WHen interrogation permits appraisal of the mouth...]. PMID- 11218305 TI - [Interactions between corticosteroids and oral anticoagulants: a real problem]. PMID- 11218306 TI - [Two faces of Kikuchi disease]. PMID- 11218307 TI - [A cause of unexplained hyperkalemia: trimethoprim-sulfamethoxazole]. PMID- 11218308 TI - [A potential etiology of elevated ferritin: hyperferritinemia-cataract syndrome]. PMID- 11218309 TI - [Unilateral exophthalmia revealing orbital myositis associated with metastatic cutaneous melanoma]. PMID- 11218310 TI - [Disseminated candidiasis in drub abusers: report of a case revealed by the presence of Candida-related pustules]. PMID- 11218311 TI - [Lymphedema and Paget's disease of the scrotum]. PMID- 11218312 TI - [Physicopathologic mechanisms and methods of analysis of cellular apoptosis]. AB - Apoptosis is a normal process occurring during development and in various tissues in humans. It appears that the mechanisms responsible for apoptosis are implicated in many aspects of human diseases. The apoptotic answer is in fact the integration of multiple different and complex signalization pathways which communicate, bifurcate and self-regulate. The mitochondria take an essential place in the description of programmed cell death and its regulation mechanisms. Caspases are the effector of apoptotic cell death. The methods of identification of the apoptosis pathways are: morphological modifications observed in microscopy, the evaluation of the difference of the mitochondrial membrane potential, the measurement of the DEVDase activity, the labelling of the phosphatidylserines by the annexin V on the cell surface, and the Western blot allowing the identification of the activated caspases. Apoptosis is implicated in many pathologies. A better understanding of the mechanisms of apoptosis and tissue specificity of the caspases make it possible to consider in the future the development of synthetic inhibitors as serious candidates for a therapeutic intervention. PMID- 11218313 TI - [Report on evaluation of clinical laboratory examination of GFR and urinary protein]. PMID- 11218314 TI - [Immunohistochemical analysis of protein gene product 9.5, a new marker for parietal epithelial cells of Bowman's capsules, in anti-glomerular basement membrane(GBM) antibody induced glomerulonephritis of WKY rats]. AB - Protein gene product 9.5(PGP 9.5) is expressed specifically in neuroendocrine cells and considered to be one of the neuroendocrine markers. Recently, we reported that PGP 9.5 is localized in the parietal epithelial cells(PECs) of Bowman's capsules as well as in neural tissues. In the present study, immunohistochemical analysis of PGP 9.5 as a specific marker of the PECs of Bowman's capsules, synaptopodin as a podocyte-specific marker, and ED-1 as a specific marker of monocytes/macrophages was performed in the cellular crescents in anti-GBM antibody induced glomerulonephritis of WKY rats using serial renal sections. In the acute phase of anti-GBM antibody induced glomerulonephritis, and the expression of PGP 9.5 and ED-1 was observed diffusely in proliferating cells of cellular crescents. However, in most part of cellular crescents, PGP 9.5 positive areas did not overlap with the ED-1 positive areas. Synaptopodin was constantly detected along the glomerular tufts compressed by the crescents. In the chronic phase of this disease, PGP 9.5 was observed in the cells covering the surface of fibrous crescents or scattered within fibrocellular crescents. Synaptopodin was partially detected in such cells. It appears that cellular crescents are composed mainly of proliferating PECs and macrophages in rat anti GBM antibody-induced glomerulonephritis. PMID- 11218316 TI - [A case of congenital nephrogenic diabetes insipidus accompanied by hypertension]. AB - Congenital nephrogenic diabetes insipidus is a rare disorder in which the kidney is insensitive to the antidiuretic hormone, vasopressin. In most cases, a mutation in the vasopressin type 2(V2) receptor gene is the genetic cause of the disease. So far, few cases of congenital nephrogenic diabetes insipidus with hypertension have been reported. We report one male case of congenital nephrogenic diabetes insipidus accompanied by hypertension. The patient was a 24 year-old man who had suffered from polyuria and polydipsia since infancy and had been found to have hypertension at about 16 years. He was admitted to hospital in May 2000 for investigation of polyuria and hypertension with a high plasma level of renin activity of 10.4 ng/ml/hr. On physical examination, the blood pressure was 150/90 mmHg and the daily urinary output was 18.5 l. There was no change in urine volume and urine osmolality after an intramascular injection of vasopressin and water deprivation. The blood pressure and plasma renin activity were increased from 127/73 mmHg to 146/87 mmHg and from 4.9 ng/ml/hr to 6.1 ng/ml/hr, respectively, by a 4-hour dehydration test. He was found to have a C-to-T transition at nucleotide position 675 by sequencing analysis of the V2 receptor gene. After administration of hydrochlorothiazide, both the blood pressure and urine volume were reduced. Consequently, it was suggested that activation of the renin-angiotensin system by dehydration, at least in part, contributed to high blood pressure in this case. PMID- 11218315 TI - [Renal hemodynamic effect of angiotensin II type 2 receptor]. AB - In the present study, the role of the angiotensin II type 2 receptor in the regulation of medullary blood flow in conscious Spontaneous Hypertensive Rats(SHR) was investigated. We tested the hypothesis that AT2 receptor activation may exert the opposite effects of AT1 receptors in terms of renal hemodynamics. Mean arterial pressure(MAP), daily sodium balance, cortical blood flow(CBF), and medullary blood flow(MBF) were measured over a 10-day protocol in several groups of rats in which optical fibers for laser-Doppler flowmetry had been implanted and which received the following drug combinations: the AT1 receptor antagonist CV11976(CV) alone and CV plus AT2 receptor antagonist PD123319 (PD). In the CV alone group, the renal interstitial administration of CV decreased MAP, caused sodium diuresis, and increased MBF significantly. In the CV plus PD group, the renal interstitial administration of PD prevented sustained hypotension, sodium diuresis, and increased medullary blood flow during CV administration. These data indicated that AT2 receptor activation leads to vasodilation in the renal medulla and an antihypertensive effect in SHR. AT2 receptors play an important role in the renal medullary blood flow. PMID- 11218317 TI - [A case of paroxysmal nocturnal hemoglobinuria combined with focal segmental glomerular sclerosis]. AB - A 81-year-old woman was admitted to our hospital because of edema and massive proteinuria on September 26, 1995. On admission, the palpebral conjuctiva were slightly anemic, and edema of the eyelids and legs was observed. Laboratory findings were as follows, urine protein(3+), occult blood(3+), WBC 2,600/microliter, Hgb 10.0 g/dl, reticulocytes 20@1000, TP 5.0 g/dl, Alb 2.7 g/dl, T-Cho 376 mg/dl, TG 194 mg/dl, LDH 763 U/l, haptoglobin < 93 mg/dl, Ham's test(+), sugar water test(+), and indirect coombs (+). The erythrocytes of this patient showed a negative population consisting of double negative erythrocytes evaluated by flow cytometric two-color analysis using monoclonal antibodies specific to CD55 and CD59. From these findings, the diagnosis of paroxysmal nocturnal hemoglobinuria(PNH) was made. The patient showed nephrotic syndrome and a renal biopsy was performed. The histological findings of renal biopsy showed focal and segmental sclerosis and adhesion of glomerular tufts. Interstitial fibrosis with atrophic tubules and lymphocyte infiltration were also observed. There was no specific staining of immunoglobulins and complement by immunofluorescence. The diagnosis of focal segmental glomerular sclerosis(FSGS) was made. There have been only three case reports of glomerular disease in patients with PNH, such as purpura nephritis, IgA nephropathy and membranous nephropathy. The complication of FSGS and PNH is every rare and there has been no report of FSGS in a case with PNH. The onset of PNH resulted from the loss of CD55 and CD59, which was critical in the onset of FSGS in the present case. PMID- 11218318 TI - [Two cases of episodic angioedema associated with eosinophilia]. AB - We experienced two cases of limb edema of unknown pathogenesis. No evidence was found concerning involvement of the kidneys, heart of other visceral organs. Case 1 was 22-year-old woman. Her white blood cell count increased to 13,100/microliter with 65.0% eosinophils. Case 2 was a 27-year-old woman. Her white blood cell count increased to 23,300/microliter with 67.0% eosinophils. In these cases, extensive diagnostic evaluations revealed no evidence of atopy, neoplasms, collagen-vascular disease, or parasitic infestation. We diagnosed these cases as episodic angioedema with eosinophilia. In both cases, the angioedema improved gradually in parallel with a decrease in the white blood cell count. This disorder is very rare, but it is very important to consider it in differential diagnosis especially for nephrologists. PMID- 11218319 TI - A primary care intervention for depression. AB - To assess a guideline-based intervention's impact on depression care provided in rural vs. urban primary care settings, 12 community primary care practices (four rural, eight urban) were randomized to enhanced (i.e., intervention) and usual care study conditions. The study enrolled 479 depressed patients, with 432 (90.2 percent) completing telephone follow-up at six months. Multilevel analytic models revealed that rural enhanced care patients had 2.70 times the odds (P = 0.02) of rural usual care patients of taking a three-month course of antidepressant medication at recommended dosages in the six months following baseline; urban enhanced care patients had 2.43 times the odds compared with their urban usual care counterparts (P = 0.007). Rural enhanced care patients had 3.00 times the odds of rural usual care patients of making eight or more visits to a mental health specialist for counseling in the six months following baseline (P = 0.03). Comparisons of patients in enhanced care practices showed that rural enhanced care patients had 2.00 times the odds (P = 0.12) of urban enhanced care patients of making at least one visit to a mental health specialist for counseling in the six months following baseline and had comparable odds to urban enhanced care patients (odds ratio [OR] = 1.06, P = 0.77) of making eight or more visits to such specialists during that interval. The study's intervention improved the care received by both rural and urban depressed primary care patients. Moreover, the intervention's effect appears to have been greater in rural settings, particularly in terms of increasing depressed rural patients' use of mental health specialists for counseling. PMID- 11218320 TI - Why rural residents migrate for family physician care. AB - Several studies have examined why rural residents bypass local hospitals, but few have explored why they migrate for physician care. In this study, data from a random mail survey of households in rural Iowa counties were used to determine how consumers' attitudes about their local health system, health beliefs, health insurance coverage and other personal characteristics influenced their selection of local vs. nonlocal family physicians (family physician refers to the family practice, internal medicine or other medical specialist providing an individual's primary care). Migration for family physician care was positively associated with a perceived shortage of local family physicians and use of nonlocal specialty physician care. Migration was negatively associated with a highly positive rating of the overall local health care system, living in town, Lutheran religious affiliation and private health insurance coverage. By understanding why rural residents prefer to bypass local physicians, rural health system managers, physicians and policy-makers should be better prepared to design innovative health organizations and programs that meet the needs of rural consumers. PMID- 11218321 TI - Utilization of preventive medical services in the United States: a comparison between rural and urban populations. AB - Differences between rural and urban residents in their utilization of three clinical preventive services--Papanicolaou screening tests (Pap smears) for women aged 18 to 65, mammograms for women aged 50 to 69 and flu shots for people aged 65 or older--were examined using a nationally representative sample from the 1994 U.S. National Health Interview Survey. Eighty-two percent of urban women and 79 percent of rural women (P = 0.11) had Pap smears. Sixty-eight percent of urban women and 61 percent of rural women (P = 0.01) had mammograms. Flu shots were received by 55 percent of urban and 58 percent of rural elderly residents (P = 0.11). Of women aged 50 to 69 who had a high school education or whose annual household income was between $15,000 and $34,999, significantly fewer rural than urban women had mammograms (P < 0.01). However, the proportion of rural women receiving mammograms was not significantly different from that of urban women after adjusting for their education, household income and health insurance status. Education level, house-hold income and health insurance coverage were positively associated with utilizing mammograms. These results suggest that differences in the utilization of preventive services between rural and urban women vary by services. Improving socioeconomic status and health insurance coverage of rural women may reduce the disparity in mammogram use between rural and urban women. Mechanisms of how a woman's socioeconomic status affects her utilization of mammograms needs further study. PMID- 11218322 TI - The role of critical access hospital status in mitigating the effects of new prospective payment systems under Medicare. AB - This article examines rural hospitals that potentially qualify as critical access hospitals (CAH) and identifies facilities at substantial financial risk as a result of Medicare's expansion of prospective payment systems (PPS) to nonacute settings. Using Health Care Financing Administration (HCFA) cost reports from the federal year ending Sept. 30, 1996, combined with county-level sociodemographic data from the Area Resource File (ARF), characteristics of potential CAHs were identified and their finances analyzed to determine whether they could benefit from the cost-based reimbursement rules applicable to CAH status. Rural hospitals were identified as potential CAHs if they met a combination of federal and state criteria for necessary providers. Rural facilities were classified as "at risk" if they had poor financial ratios in conjunction with high levels of dependence on outpatient, home-care or skilled nursing services. Almost 30 percent of all rural hospitals were identified as potential CAHs. Ninety percent of potential CAH facilities were identified as "at risk" by at least one of five possible risk criteria, and one-third were identified by at least three. Of those classified "at risk," 48 percent might not benefit from conversion to CAH because their inpatient Medicare reimbursement would likely be less under CAH payment rules than under their current PPS payment rules. Many potential CAHs were doing well under inpatient PPS because they were sole community hospitals (SCH) and were therefore eligible for special adjustments to the PPS rates. The Rural Hospital Flexibility Act would be more beneficial to the population of isolated rural hospitals if those eligible for both CAH and SCH status were given the option of retaining their SCH inpatient payment arrangements while still qualifying for outpatient cost-based reimbursement. PMID- 11218323 TI - Moving from medical student placement to a community-academic partnership with a rural community. AB - This article explains a partnership-based community education model, which uses as an example a partnership between the Center for Healthy Communities in the Department of Family and Community Medicine at the Medical College of Wisconsin (MCW) and the rural Marion area of central Wisconsin. MCW is similar to other medical schools in that it has a strong history and philosophy of placing students in communities for educational purposes. This article describes how the Center for Healthy Communities is moving beyond student placement to true partnership building. The center followed four stages of development as it built a partnership with this rural Wisconsin community: (1) establish and build relationships, (2) develop common goals, (3) develop and implement programs and (4) maintain and expand progress. The center also applied a set of principles in developing the partnership. By following the stages and applying the principles, the center found that two elements were key to building a partnership for medical student education and community health improvement: long-term commitment and ability and willingness to spend time in the community. As a result, a meaningful, ongoing partnership developed that benefits both the community and MCW. PMID- 11218324 TI - Implementing the latest "guidelines" may not be easy. PMID- 11218325 TI - If we want to change unfair Medicare payment, there may never be a better opportunity. PMID- 11218326 TI - Rift Valley Fever, Yemen (update). PMID- 11218327 TI - Recommended composition of influenza virus vaccines for use in the 2001 influenza season. PMID- 11218328 TI - Malaria research. PMID- 11218329 TI - Ebola, Uganda. PMID- 11218330 TI - Human plague in 1998 and 1999. PMID- 11218331 TI - Integrated global effort against malaria. PMID- 11218332 TI - Oral poliovirus vaccine (OPV) and intussusception. PMID- 11218333 TI - Legionnaires' disease, Europe, 1999. PMID- 11218334 TI - Malaria risk for travellers to Africa. PMID- 11218335 TI - Circulation of a type 2 vaccine-derived poliovirus, Egypt. PMID- 11218336 TI - Chiangmai declaration on dengue/dengue haemorrhagic fever. Strengthening efforts to control dengue in the new millennium. PMID- 11218337 TI - BCG in immunization programmes. PMID- 11218338 TI - Cognitive, perceptual-speed, and psychomotor determinants of individual differences during skill acquisition. AB - The authors describe a series of experiments that explore 3 major ability determinants of individual differences in skill acquisition in the context of prior theory (e.g., P.L. Ackerman, 1988) and subsequent empirical and theoretical research. Experiment 1 assessed the predictability of individual differences in asymptotic skill levels on the Kanfer-Ackerman Air Traffic Controller (ATC) task. Experiment 2 provided an exploration of the construct space underlying perceptual speed abilities. Experiment 3 concerned an evaluation of theoretical predictions for individual differences in performance over skill development in a complex air traffic control simulation task (TRACON) and the ATC task, with an extensive battery of general and perceptual-speed measures, along with a newly developed PC based suite of psychomotor ability measures. Evidence addressing the predictability of individual differences in performance at early, intermediate, and asymptotic levels of practice is presented. PMID- 11218339 TI - Exploring the effects of icon characteristics on user performance: the role of icon concreteness, complexity, and distinctiveness. AB - Because icons, signs, and symbols are now widely used to communicate information, it is essential for system designers to know what makes them easy to use and interpret. The authors report a series of studies that examine characteristics considered central to icon usability. After quantifying the properties of icon concreteness, complexity, and discriminability, the authors assessed each property's effects on user performance when user experience, task demands, and presentation context were systematically varied. Findings indicated that the effects of icon concreteness were primarily associated with the initial grasp of meaning, whereas complexity effects were found to persist longer and to be associated with search efficacy. The effects of icon distinctiveness were complex, but distinctiveness was enhanced by using both semantic and visual contrasts. The implications of these findings for interface design are discussed. PMID- 11218340 TI - Individual differences in spatial learning from computer-simulated environments. AB - A multivariate study examined relationships between the following factors: paper and-pencil assessments of verbal and spatial ability, ability to form an accurate spatial representation of a large real-world environment, gender, computer attitudes and experience, proficiency with the navigational interface of a virtual environment (VE), and the ability to acquire and transfer spatial knowledge from a VE. Psychometrically assessed spatial ability and proficiency with the navigational interface were found to make substantial contributions to individual differences in the ability to acquire spatial information from a VE. Gender influenced many VE-related tasks, primarily through its relationship with interface proficiency and spatial ability. Measures of spatial knowledge of a VE maze were highly predictive of subsequent performance in a similar real-world maze, suggesting that VEs can be useful for training people about real-world spaces. PMID- 11218341 TI - Milliseconds matter: an introduction to microstrategies and to their use in describing and predicting interactive behavior. AB - Interactive behavior is constrained by the design of the artifacts available (e.g., a mouse and button) as well as by the ways in which elementary cognitive, perceptual, and motor operations can be combined. Any 2 basic activities, for example, (a) moving to and (b) clicking on a button, can be combined to yield a limited number of microstrategies. The results of an experimental study suggest that alternative microstrategies can be deployed that shave milliseconds from routine interactive behavior. Data from a usability study are used to explore the potential of microstrategies for (a) bracketing the range of individual performance, (b) profiling individual differences, and (c) diagnosing mismatches between expected and obtained performance. These 2 studies support the arguments that the microstrategies deployed can be sensitive to small features of an interface and that task analyses at the millisecond level can inform design. PMID- 11218342 TI - Illusory correlations in graphological inference. AB - The authors investigate the illusory correlation phenomenon as a possible contributor to the persistence of graphology's use to predict personality. Participants unfamiliar with graphology inspected handwriting samples paired with fabricated personality profiles. In Experiment 1, handwriting samples and personality profiles were randomly paired. In Experiment 2, discernible correlations near unity were set between targeted handwriting-feature-personality trait pairs in a congruent or incongruent direction with graphologists' claims. In both experiments, participants' judgments of the correlation between designated handwriting-feature-personality-trait pairs agreed with graphologists' claims, even after controlling for their actual statistical association. Semantic association between words used to describe handwriting features and personality traits was the source of biases in perceived correlation. Results may partially account for continued use of graphology despite overwhelming evidence against its predictive validity. PMID- 11218344 TI - The supply side initiative as an international collaboration to study alcohol supply, drinking, and consequences: current knowledge, policy issues, and research opportunities. PMID- 11218343 TI - Preference between onset predictable and unpredictable administrations of 20% carbon-dioxide-enriched air: implications for better understanding the etiology and treatment of panic disorder. AB - Predictability of aversive events impacts the development and maintenance of anxiety, particularly panic disorder. Although animal studies typically have found a preference for signaled (predictable) over unsignaled (unpredictable) aversive events, results of research with human participants have been less clear. Using a panic-relevant paradigm, the authors examined predictability preference with humans as a function of anxiety sensitivity and gender during repeated administrations of 20% carbon-dioxide-enriched air. Participants preferred predictable administrations, with high-anxiety individuals showing greater preference than low-anxiety individuals and women showing greater preference than men. In addition to providing information to better understand human predictability preference for panic-related events, results also may aid in determining the applicability of predictability to the cognitive-behavioral treatment of panic disorder. PMID- 11218345 TI - Applying commodity chain analysis to changing modes of alcohol supply in a developing country. AB - Development sociology has used global commodity chains as one way of analyzing the dynamics of power and profit-taking in globalized production networks made up of multiple firms and occurring in multiple national settings. A substantial portion of the alcohol supply in developing countries is now produced through such production networks. Particularly in the beer and spirits trade, a small number of transnational firms control networks of local producers, importers, advertisers and distributors. These networks serve to embed transnational or transnationally backed brands in the local culture, using the tools of market research, product design and marketing to influence local drinking practices. Case materials from Malaysia's beer industry help to illustrate how the transnational firms dominate in those links of the commodity chain in which monopoly or oligopoly control is most likely to be found: the design/recipe and marketing/advertising nodes. Their control of the commodity chains and extraction of monopoly or oligopoly profits from them places substantial resources and influence over drinking settings and practices in foreign hands. The impact of this influence on state efficacy and autonomy in setting alcohol policy is an important subject for future research on the creation and implementation of effective alcohol policies in developing societies. PMID- 11218346 TI - International issues in the supply of tobacco: recent changes and implications for alcohol. AB - This paper reviews international issues in the supply of tobacco and tobacco products, including trade liberalization and globalization. The paper begins with a brief discussion of the theoretical foundations for trade and trade restrictions. This is followed by a description of the treatment of tobacco and tobacco products in recent multi-lateral, regional and bilateral trade agreements, as well as a short discussion of the recent globalization of the tobacco industry. Included in this description is a review of the empirical evidence on the impact of trade liberalization on tobacco use. The implications of two recently proposed international agreements--the Multilateral Agreement on Investments and the Framework Convention for Tobacco Control--are then discussed. The paper concludes by summarizing the theoretical and empirical evidence that shows clearly that trade liberalization has significantly increased tobacco use, particularly in low and middle-income countries, and follows this with a discussion of the lessons learned from tobacco for controlling alcohol supply. PMID- 11218347 TI - Impacts of international trade, services and investment treaties on alcohol regulation. AB - There is an underlying incompatibility between government efforts to minimize the harm associated with alcohol, particularly by regulating its supply, and international commercial treaties that promote the freer flow of goods, services and investment. These treaties have already forced changes to many government measures affecting alcohol availability and control, primarily by constraining the activities of government alcohol monopolies and by altering taxation regimes. The North American Free Trade Agreement and the World Trade Organization agreements open new avenues for challenges against alcohol control measures. Some of these agreements extend beyond trade, border measures and differential taxation and allow challenges that intrude into areas of non-discriminatory domestic regulation affecting market access, intellectual property, investment and services. Effective protection from these agreements for vital public health measures has rarely been obtained, although it is increasingly essential. The WTO "services" agreement, basically unknown to the public, is currently being re negotiated and poses the gravest new challenge to policies designed to influence patterns of alcohol use and minimize alcohol-related harm. In future, these international agreements will probably affect adversely those alcohol approaches considered to be the most effective or promising. These include: maintaining effective state monopolies, restricting the number and locations of retail outlets, taxing and regulating beverages according to alcohol strength, restricting commercial advertising, and maintaining and enhancing public alcohol education and treatment programs. These effects can, in turn, be expected to increase the availability and access to alcohol, to lower alcohol taxes, and to increase advertising and promotion, resulting in increased alcohol consumption and associated health problems. Until more balanced international rules are developed, the challenge facing alcohol policy researchers is to defend national and local alcohol measures from further erosion. This will require greater coordination with researchers in other affected sectors, intervention with government representatives in health and related areas and the promotion of alternative approaches to current international commercial agreements. PMID- 11218348 TI - The supply of alcoholic beverages in transitional conditions: the case of Central and Eastern Europe. AB - Three periods are distinguished and applied to describe the dynamics of changes in the system of supply of alcoholic beverages in Central and Eastern Europe since 1980. The distinction of these three periods is based on changes in the regulation of the supply. The period of the old regulation ended in most countries around the 1990s. A deregulation took place in the early 1990s. The first steps toward a reregulation were visible in attempts to create a new order in the alcohol market in the last years of the 1990s. The analysis builds mainly on developments in Poland and Russia, with more scattered information from other countries. In each period the role of different actors (the state, the enterprises, organized crime, civil organizations and individuals), different interests (economic development, state finances, political order, public order, public health and various symbolic interests) and different public measures to regulate the supply (licensing, taxation and preventive actions and treatment) are considered. The analysis shows how the state lost its dominant position to private firms and is slowly regaining it again, how interest in state finances, overall economic development and later in profit-making dominate all three periods, and how the old system of regulations was ruined, to become rebuilt in very small steps with many conflicts and complications. Public health interests and also civil society interests were weak in comparison with economic interests. From the public health perspective, changes in the supply system have had significant consequences, but a more comprehensive regulation of supply does not necessarily lead to diminished alcohol-related harm. PMID- 11218349 TI - The ambiguous role of alcohol in economic and social development. AB - An increased and industrialized alcohol supply in a developing society is usually assumed to have positive effects on economic development, although it may be recognized that the effects on public health and order will be negative. There has been little attention to the potential for negative effects on the economic side. This paper directs attention to such factors as unemployment for cottage producers (often female heads of household) and reduced industrial employment as highly-automated "turnkey" brewers are installed. On the other hand, changes in the mode of production of alcoholic beverages may have little impact on the much larger work-force involved in serving or selling alcohol in retail trade. The net contribution of an increased and industrialized alcohol supply in terms of economic development is unclear, but industrialization and development bring with them increased demands for attention and sobriety, e.g. in motorized traffic and on the production line, which increased drinking may undercut. Decisions by international development agencies on investment in alcohol production and distribution should take account of both the positive and negative impacts on economic development as well as on public health. In line with this, the World Bank has recently decided to invest in alcohol industry projects only when there is a strong positive development impact and the project is "consistent with public health issues and social policy concerns". PMID- 11218350 TI - Local and global alcohol supply: economic and geographic models of community systems. AB - This paper discusses how economic and geographic distributions of local supply affect patterns of alcohol problems in state and community settings. It is argued that characteristics of local supply directly affect the economic and social behaviors of consumers when purchasing and using alcohol. For example, although taxes may be raised in order to lower alcohol use, the manner in which tax increases are translated into price increases, and the way consumers respond to price increases through alterations in purchase patterns, may strongly mitigate price effects. Similarly, although overall alcohol availability may be reduced in order to lower alcohol use, the tendency for greater numbers of outlets to be focused in low-income areas and the manner in which consumers bundle alcohol purchases with other routine activities (e.g. shopping) may also strongly mitigate such effects. PMID- 11218351 TI - Unrecorded alcohol consumption: its economics and its effects on alcohol control in the Nordic countries. AB - The starting point of this paper is the fact that no country has complete records of alcohol consumption. In addition to being a matter or statistical accuracy, unrecorded alcohol also plays an important role in alcohol policy discussions. Furthermore, its quantity is bound to basic economic laws. These latter two aspects are the main interest in this paper, which discusses, first, what is really meant by unrecorded alcohol consumption and what kind of categories are included in it. The next task is to discuss the economics of different categories of unrecorded alcohol and the mechanisms which lead to increases or decreases in them. The examples in this part of the paper come from the Nordic countries. Arguments about increased smuggling and illegal distilling have always been used against alcohol policy restrictions in the Nordic countries. Recently the level of travellers' alcohol imports and border trade have also been used for the same purpose. In the European Union the task to harmonize alcohol excise taxes is partly given to increased travellers' duty-free allowances and market forces. This policy has already led to reductions in alcohol taxation both in Denmark and Sweden. PMID- 11218352 TI - The influence of economic interests on alcohol control policy: a case study from Finland. AB - Finland's participation in the European Union has meant that Finnish markets have been opened to international competition and that the traditional alcohol policy decision-making that revolved around Alko, the state alcohol monopoly company, has become impossible. The influence of private commercial interests increased in the 1990s but not in a straightforward manner. They had their biggest influence in the mid-1990s when the 1994 Alcohol Act was drafted and accepted. After that the influence of commercial interests has declined, and nowadays the alcohol question is again discussed in terms of public health and safety and drinking among young people. Integration did not lead to the expected deregulation of alcohol control but to new forms of regulation, where EU authorities such as the Commission and the EU Court also play an important role. Alcohol policy-making is now more transparent, and free trade and competition without interference are much more stressed than previously. These are the new frames of public intervention in the alcohol question, both in the trade of alcoholic beverages and in the taking care of individuals harmed by the use of alcohol. PMID- 11218353 TI - Roles of commercial interests in alcohol policies: recent developments in North America. AB - This paper examines recent developments in Canada and the United States and the role of commercial interests in alcohol-related policies bearing on taxes, outlet density, advertising, counter-advertising, health messages and prevention. Case study material is drawn from published papers, project reports, government documents and newspaper accounts. The main focus is at the federal level, with some reference to provincial, state and local experience. Alcohol industries have as their primary agenda that of maintaining and expanding their markets and maximizing profits. In order to achieve this they typically oppose restrictions on access to alcohol, tax increases, controls on marketing and some counter advertising campaigns. They are powerful in influencing policy in both countries, at national and regional levels, and their efforts impact policy agenda and outcome of government deliberations. Their prevention efforts, which tend to be oriented to information and education, are mainly individualistic in focus and typically not supportive of environmentally based policy reforms. Governments appear to have a declining interest in policy issues, due partly to resistance by the industries to alcohol control policies. Governments are encouraged to apply an evidence-based orientation to funding prevention, and facilitate evaluation of industry-sponsored prevention efforts. Greatest attention and resources should be directed to interventions that are most likely to have the greatest impact in reducing drinking-related problems, and funding for prevention from alcohol industries should involve arms-length arrangements. Alcohol industries are encouraged to consider strategies that do not increase access to alcohol but rather reduce drinking-related risks. PMID- 11218354 TI - Marketing alcohol to young people: implications for industry regulation and research policy. AB - This paper focuses on the marketing of alcohol to young people in the United Kingdom, but the lessons that emerge have international significance. Alcohol is a global enterprise and recent consolidation means that it is controlled by a decreasing number of expanding multi-nationals. Alcohol companies are able to allocate significant resources to researching consumer preferences, developing new products and promoting them on an international level. Recent years have seen a growth in the value that youth culture attaches to brand labels and symbols and a move away from the healthy-living ethos. The alcohol industry's response to these trends has been to design alcoholic beverages that appeal to young people, using well-informed and precisely targeted marketing strategies. This has led to growing concerns about the implications for public health and a demand for tighter controls to regulate alcohol marketing practices. In the United Kingdom, controls on alcohol are piecemeal and reactive and the current system of voluntary regulation appears ineffective. This paper argues for more research to establish current industry practice and inform the development of a comprehensive regulatory structure and system of monitoring. PMID- 11218355 TI - Alcopops in Sweden--a supply side initiative. AB - This paper describes the introduction of alcopops and sweet ciders in Sweden in 1996, as a result of the membership of the European Union. Special attention is given to its effect on youth drinking. Surveys of young people show that alcopops and sweet ciders are perceived to be easy to drink and to have a sweet and pleasant taste, which tends to conceal the taste of alcohol. These results suggest that alcopops and sweet ciders should be regarded as one category of drinks. Alcopops and sweet ciders have penetrated the youth market rapidly. The introduction of these beverages accounted for approximately half of the increase in alcohol consumption by 15-16-year-old boys from 1996 to 1999, and two-thirds of the increase among girls, according to the surveys. A large proportion of the youth answered that alcopops and ciders did not replace any other alcoholic beverage. The paper also describes the public debate on alcopops and cider. The introduction of alcopops was criticized by the media and the responsible minister. Prominent spokesmen of the alcohol industry put themselves at a distance from these, primarily imported, products. The sales of alcopops have been declining since 1997. Sweet ciders, on the other hand, which in reality are synonymous with alcopops, have continued to increase during the whole period since 1996, and have not been subject to the same public criticism. PMID- 11218356 TI - The alcohol supply: its importance to public health and safety, and essential research questions. AB - This paper seeks to identify the main questions which have emerged from the preceding papers concerning the supply side of alcohol. On any rational analysis these issues are of thoroughly legitimate concern to public health researchers. We list them under seven headings: (1) what drives the alcohol supply side? (2) What is the impact of alcohol supply on demand? (3) What are the benefits and risks to health and safety stemming from deregulation and what are the possibilities to avoid negative effects? (4) What is the size and significance of the alcohol supply which may derive from other than the officially approved channels? (5) Who are the important actors in the alcohol supply system? (6) What are local influences on alcohol supply and its distribution throughout communities? (7) What is to be learned from tobacco and other risky commodities about the importance of supply? Finally, we outline a series of possible next steps for a supply side initiative. PMID- 11218357 TI - Professional ethics and marketing of treatment. PMID- 11218358 TI - UROD: an antipodean therapeutic enthusiasm. PMID- 11218359 TI - Large claims obstruct progress. PMID- 11218360 TI - Dissemination of current treatment research findings to the profession, policy makers and patients--whose responsibility is it? PMID- 11218361 TI - Our ethical responsibility. PMID- 11218362 TI - Warning label: this treatment approach may cause claims of a magic cure. PMID- 11218363 TI - Overvalued ideas about alcoholism and schizophrenia. PMID- 11218364 TI - The co-occurrence of schizophrenia and alcoholism: comments on Michael Soyka's editorial. PMID- 11218365 TI - Injectable methadone: cautious interest. PMID- 11218366 TI - Naloxone distribution: remembering hepatitis C transmission as an issue. PMID- 11218367 TI - Putting thiamine in beer: comments on Truswell's editorial. PMID- 11218368 TI - Alcoholism treatment and the importance of economic analysis: comment on Holder et al. PMID- 11218369 TI - When commercial interests differ from public health interests: comments on Sato et al. PMID- 11218370 TI - Conflict of trade versus health: problems and prospects. PMID- 11218371 TI - Use of race and ethnicity in epidemiologic research: concepts, methodological issues, and suggestions for research. PMID- 11218372 TI - Molecular epidemiology of vitamin D receptor gene variants. PMID- 11218373 TI - HLA-DQ locus of the human leukocyte antigen complex and type 1 diabetes mellitus: a HuGE review. PMID- 11218374 TI - Review of organizational factors related to care offered to women with breast cancer. PMID- 11218375 TI - Perinatal sex hormones and risk of breast and prostate cancers in adulthood. PMID- 11218376 TI - Reproductive problems among women health care workers: epidemiologic evidence and preventive strategies. PMID- 11218377 TI - Epidemiology of gestational weight gain and body weight changes after pregnancy. PMID- 11218378 TI - Birth weight in offspring of women with epilepsy. PMID- 11218379 TI - Helicobacter pylori: epidemiology and routes of transmission. AB - H. pylori is a common bacterium, and approximately 50 percent of the world's population has been estimated to be infected (198). Humans are the principal reservoir. The prevalence of H. pylori infection varies widely by geographic area, age, race, ethnicity, and SES. Rates appear to be higher in developing than in developed countries, with most of the infections occurring during childhood, and they seem to be decreasing with improvements in hygiene practices. H. pylori causes chronic gastritis and has been associated with several serious diseases of the gastrointestinal tract, including duodenal ulcer and gastric cancer. Since its "discovery" in 1982 by Warren and Marshall (1), H. pylori has been the topic of extensive research. A number of studies have used questionnaire components to investigate factors possibly related to the etiology of H. pylori infection. The majority of recent studies have not found tobacco use or alcohol consumption to be risk factors for H. pylori infection. Adequate nutritional status, especially frequent consumption of fruits and vegetables and of vitamin C, appears to protect against infection with H. pylori. In contrast, food prepared under less than ideal conditions or exposed to contaminated water or soil may increase the risk. Overall, inadequate sanitation practices, low social class, and crowded or high-density living conditions seem to be related to a higher prevalence of H. pylori infection. This finding suggests that poor hygiene and crowded conditions may facilitate transmission of infection among family members and is consistent with data on intrafamilial and institutional clustering of H. pylori infection. Understanding the route of H. pylori transmission is important if public health measures to prevent its spread are to be implemented. Iatrogenic transmission of H. pylori following endoscopy is the only proven mode. For the general population, the most likely mode of transmission is from person to person, by either the oral-oral route (through vomitus or possibly saliva) or perhaps the fecal-oral route. The person-to-person mode of transmission is supported by the higher incidence of infection among institutionalized children and adults and the clustering of H. pylori infection within families. Also lending support to this concept is the detection of H. pylori DNA in vomitus, saliva, dental plaque, gastric juice, and feces. Waterborne transmission, probably due to fecal contamination, may be an important source of infection, especially in parts of the world in which untreated water is common. Recent studies in the United States have linked clinical H. pylori infection with consumption of H. pylori contaminated well water. This area of research is worthy of further investigation. Although H. pylori has been isolated in domestic cats, additional research has suggested that H. pylori is probably uncommon in domestic cats and thus is probably not a major concern for cat owners. Several studies have suggested sheep as a possible source of H. pylori transmission, a hypothesis that deserves additional investigation. The most recent reservoir suggested for H. pylori transmission is the housefly. However, evidence is lacking that H. pylori can be transmitted to humans from flies that have been in contact with H. pylori infected feces. Nevertheless, the hypothesis is appealing since flies are known to carry many other infectious diseases. Knowledge of the epidemiology and mode of transmission of H. pylori is important to prevent its spread and may be useful in identifying high-risk populations, especially in areas that have high rates of gastric lymphoma, gastric cancer, and gastric ulcer. PMID- 11218380 TI - Differential diagnosis of acute flaccid paralysis and its role in poliomyelitis surveillance. PMID- 11218382 TI - [Isolation of methicillin-resistant Staphylococcus aureus from nasopharyngeal swabs on admission to a ward for pediatric patients: comparison between 1992-1993 and 1997-1998]. AB - We studied 2,176 nasopharyngeal swabs obtained from 1,891 children on admission to the pediatric ward at Asahikawa Kosei Hospital from January 1997 to December 1998, and compared the results with the same study from January 1992 to December 1993. Fifty strains of Methicillin-resistant Staphylococcus aureus (MRSA) were isolated from 46 patients. The ages of these patients ranged from 7 days to 17 years and 24 patients were younger than 1 year. Six patients were diagnosed as MRSA infection; acute otitis media in 3, osteomyelitis and bacteremia in 1, staphylococcal scalded skin syndrome in 1, and inflammation in umbilical region in 1. The ratio of MRSA positive to the total specimens significantly increased from 1.25% in 1992-1993 to 2.30% in 1997-1998 (p = 0.011). The ratio of MRSA positive to the total S. aureus positive specimens significantly increased from 10.7% in 1992-1993 to 20.3% in 1997-1998 (p = 0.003). These findings demonstrated that prevalence of MRSA carriers among children is increasing. PMID- 11218381 TI - [Susceptibility testing of clinical strains of Legionella spp. isolated in Japan]. AB - We determined antimicrobial susceptibilities of 23 strains of Legionella spp. clinically isolated in Japan, between September 1994 through November 1999 by using Etest. The MICs of all isolates against macrorides, fluoroquinolones and rifampicin showed 1 microgram/ml or less. Especially rifampicin showed the most potent activity, of which the MICs of all isolates showed 0.064 microgram/ml or less. Although we could not find resistant strains against any antibiotics tested in this study, we think it is important to follow up the susceptibilities of clinical isolates of Legionella. PMID- 11218383 TI - [Experimental study on the influence of alginate induced immune complex on BALF cells]. AB - Immune complex containing alginate and antialginate antibodies plays an important role in the disease-progress of chronic airway infection with mucoid-alginate producing strains. For the purpose of clarifying the immune-pathogenic influence of the alginate induced immune complex (alg-IC) on inflammatory cells in bronchoalveolar lavage fluid (BALF), an experimental study was performed. The alginate immunized mice were injected through the trachea with alg-IC extracted from the immunized mouse serum in advance, and the changes in BALF-cells, such as macrophage, neutrophil, lymphocyte, CD16/32 positive neutrophil, CD4+ lymphocyte, CD4+CD45+ lymphocyte, CD8+ lymphocyte, CD8+CD11b- lymphocyte were investigated along with the passage of time as compared with those of the non-immunized mice. 1) On the 2nd day after intratracheal injection, the time which was chosen as an acute phase, the total count of macrophages, neutrophils, lymphocytes were increased in both groups. However CD16/32 positive neutrophil (with the expression of Fc-gamma recepter on it) was significantly decreased in the immunized group. 2) On the 5th day being chosen as the resolving phase of acute inflammation, the number of the increased inflammatory cells tended to recover to the base line value in both groups. But the continuous decrease in CD16/32 positive cell and the significant increase in CD4+CD45+ lymphocytes were found in only the immunized group. 3) On the 16th day being chosen as the beginning of the chronic phase, all inflammatory cells investigated in the non-immunized group recovered to the base line level. In the immunized group, however, significantly higher values of neutrophil-count still remained, in spite of the decrease in CD 16/32 positive neutrophils. Also, CD4+CD45+, CD8+, CD8+CD11b- lymphocytes were significantly at a higher level. 4) Histological findings in the lung tissue was supported the above findings. 5) From the above, in the alginate immunized group, the scavenging function of neutrophils for the alg-IC deposited in lung tissue would be suppressed resulting from the decrease in CD16/32 positive neutrophils, in spite of the increase in total count of neutrophils. Consequently, long term deposition of alg-IC in the lung would induce an accumulation of cytotoxic CD8+ T lymphocyte or other lymphocytes as one of the cell-mediated immune responses. This indicates that such a harmful immune reaction induced by alg-IC leads the chronic infection with mucoid-alginate producing pathogens to be more intractable. PMID- 11218384 TI - [Clinical significance of eosinophilic cationic protein in serum and bronchoalveolar lavage fluid of adult patients with mycoplasmal pneumonia]. AB - Pathogenic mechanisms of mycoplasmal pneumonia is not fully understood at present though some kind of cell-mediated hypersensitivity is closely related to its mechanisms. Though eosinophilia in peripheral blood are sometimes revealed in patient with mycoplasmal pneumonia, it is not unclear whether eosinophils related to its pathogenesis, or not. We evaluated the clinical significance of ECP in serum and BAL fluid in patients with mycoplasmal pneumonia. The diagnosis of mycoplasmal pneumonia was confirmed both by serological diagnosis from paired serum and by the polymerase chain reaction (PCR) methods using specific primers of the Mycoplasma pneumoniae for detecting specific DNA from bronchial washing fluids. ECP level in serum were measured in 27 patients (11 male, 16 female, average age 31.7 yo) with mycoplasmal pneumonia by ELISA methods. ECP level in BALF were also measured in ten of all patients. The level of ECP in serum was high in 17 cases (63%) of the total cases. In addition the level of ECP in BALF was also high in all tested patients (10 cases). There was a correlation between serum ECP level and days from onset. There was also a correlation between serum ECP level and WBC counts, the degree of PaO2. These results suggested that ECP derived from activated eosinophils in the lung might in part play a role in the pathogenesis of mycoplasmal pneumonia. PMID- 11218385 TI - [Comparison of community-acquired pneumonia in relation to influenza A and RS virus infections]. AB - We experienced 142 cases with community-acquired pneumonia between April 1998 and March 2000. By measuring the titers of respiratory viruses for these cases, we were able to identify acute phase infections of influenza A virus in 10 cases and RS virus in 6 cases and determined that there was an increase in community acquired pneumonia during both winter seasons. Thereafter we compared the clinical features of community-acquired pneumonia with regard to these two types of virus infection by dividing the patients into two groups, both of which frequently included in the elderly. In the influenza virus group, such general symptoms as high fever, headache and general fatigue were dominant. Common bacteria were isolated in nine cases with mixed infection; four of them with Streptococcus pneumoniae. In the RS virus group, there were fewer general symptoms and common bacteria were isolated in four cases with mixed infection; three with Haemophilus influenzae. The severity of the illness was greater in the Influenza virus group; i.e.) three cases required mechanical ventilation and two of these three cases died. In the RS virus group, on the other hand, the prognosis was good because no mechanical ventilation was required and there were no deaths. Influenza vaccination is especially important for the elderly, because the epidemiology of the influenza virus groups showed none had a history of influenza vaccination in this study. PMID- 11218387 TI - [Detection of spotted fever group rickettsiae DNA from ticks in Kanagawa, Shimane and Kochi Prefectures]. PMID- 11218386 TI - [Two cases of typhoid fever with reduced susceptibility to fluoroquinolones]. AB - Two separate febrile Indian patients who reside in Japan and had recently returned from their country were diagnosed as suffering from typhoid fever. Fluoroquinolone therapy was clinically ineffective and the addition of a third generation cephalosporin was required in each case. Each strain of Salmonella Typhi was resistant to nalidixic acid in vitro and also showed higher minimal inhibitory concentration to other quinolones than usual susceptible strains. Similar cases of typhoid fever responding poorly to quinolone treatment have been observed in the Indian subcontinent, south-east Asia and central Asia since the early 1990s, and potential spread by travelers into Japan is of serious concern. Although quinolones still remain the drugs of choice for treatment of typhoid fever, physicians should be aware of the possibility and implications of clinical treatment failure. PMID- 11218388 TI - [Detection of mupirocin resistant staphylococci from patients treated with mupirocin]. AB - Susceptibility testing of mupirocin (MUP) was performed by an agar dilution method according to the National Committee for Clinical Laboratory Standard (NCCLS) to detect the MUP resistance. A total of 434 isolates of methicillin resistant staphylococci were examined and all of 205 isolates of methicillin resistant Staphylococcus aureus (MRSA) from 43 hospitals nationwide in 1993 were sensitive to MUP. However, MUP resistance emerged among 228 isolates [185 isolates (88 cases) of MRSA and 43 isolates (28 cases) of methicillin-resistant coagulase negative staphylococci (MR-CNS)] from nasal swabs of patients with MUP treatment between Sep 1996 and Feb 2000 in the Nagoya University Hospital. The high-level MUP resistance (MIC > or = 512 micrograms/mL) was isolated from two patients, one isolate of MRSA and four of S. hominis, respectively. Low-level MUP resistance (MIC 8-128 micrograms/mL) was isolated from three patients, 11 isolates of MRSA, one of S. chromogenes and five of S. epidermidis, respectively. The mupA which encodes the MUP resistant isoleucyl-tRNA synthetase (IRS) were investigated by PCR in these MUP resistant isolates. The mupA was detected only in high-level MUP resistant S. hominis, but not detected in high-level MUP resistant MRSA and low-level MUP resistant isolates. We also investigated the characteristics of the patients with MUP resistance. All of MUP resistant staphylococci were isolated after initiation of MUP treatment. Four patients with MUP resistant MRSA and low-level MUP resistant MR-CNS had MRSA infectious disease and MUP resistant strains were successfully eradicated with vancomycin treatment in two patients. MUP high-level resistant S. hominis, has emerged after MUP treatment for eradication of MRSA. Clinical guidelines for the prudent use of MUP should be generally adopted with careful monitoring of emergence of MUP resistance. PMID- 11218389 TI - [Progress of molecular bacteriological studies on Helicobacter pylori]. AB - To understand pathogenesis of H. pylori in stomach diseases including gastric cancer, molecular bacteriological studies are important. The studies are greatly advanced by information of the whole genome sequence of this bacterium in 1997. Various methods of gene manipulation to identify the genes involved in pathogenesis are now available such as transformation followed by construction of knockout mutants, complementation using H. pylori-E. coli shuttle vectors, random insertion mutagenesis, and RT-PCR or proteome analysis of in vivo-expressed genes. The molecular mechanism of persistent infection of H. pylori is discussed in light of recent findings on molecular mechanisms of bacterial attachment and colonization as well as on gastric physiology. PMID- 11218391 TI - [Epidemiology of H. pylori infection]. AB - Prevalence rates and risk factors for H. pylori infection have been reported in many countries over the past year. Infection patterns in developed and developing countries are very different. Very high infection rates in developing countries with high incidence of gastric cancer were described, however, African enigma is still under controversy. The main risk factors for H. pylori infection are fecal oral and oral-oral spread because H. pylori has not been detected to any extent in the environment. Recently, in childhood, main risk factors for transmission may be the contact with own father with H. pylori infection in Japan. Re infection are very rare in adults, but not uncommon in childhood. Prevalence of H. pylori infection is reviewed. PMID- 11218390 TI - [Virulence gene of H. pylori]. AB - H. pylori is a well-recognized pathogen that infects up to 50% of humans in the world. H. pylori lives for decades in the hostile environment of the human stomach. H. pylori is closely associated with histologic gastritis, gastric ulceration, duodenal ulceration, gastric cancer and MALT lymphoma. These various clinical outcomes are considered by 1) different virulence, 2) host response, 3) other environmental factors, and their interactions. Since the whole genome was sequenced in 1997, the virulence genes have been investigated in molecular genetic aspects. The cag pathogenicity island (cagPAI) is a complex of virulence genes, which code approximately 30 proteins. The cagPAI acquired by horizontal transfer and is coding for type 4 secretion machinery system. Via this system, many virulence gene products or other interactive proteins are transferred into the host cells. PMID- 11218392 TI - [Causal relationship between Helicobacter pylori infection and upper gastroduodenal diseases]. AB - Helicobacter pylori infection causes chronic gastritis (nonatrophic gastritis), which progresses to atrophic gastritis and intestinal metaplasia over a period of decades. Atrophy may result from inflammation and apoptosis caused by H. pylori infection. H. pylori is an important risk factor for peptic ulcer disease. Duodenitis in the gastric metaplasia of the duodenum, hypergastrinemia, and impaired proximal duodenal mucosal bicarbonate secretion are considered causal factors for duodenal ulcer disease. Low-grade B-cell gastric lymphoma of mucosa associated lymphoid tissue (MALT) develops in response to H. pylori infection. Studies of Mongolian gerbil model demonstrated that H. pylori had an initiator or promoter effect on gastric carcinogenesis. PMID- 11218393 TI - [Recent guidelines for the management of Helicobacter pylori infection]. AB - The guidelines for the diagnosis and treatment of H. pylori infection have been developed in Europe, United States, Asia, and Japan. Each guideline is characteristic in recommended indication, diagnostic method, and eradication regimen, because it depends on different background of medical situation. Two guidelines were reported in 2000. One is Maastricht 2-2000 consensus report, another is the guideline of Japanese Society for Helicobacter Research. In this article, European and Japanese recent statement for the management of H. pylori infection were introduced to reveal the differences in indication, diagnosis, and treatment between both guidelines. PMID- 11218394 TI - [Triple site biopsy under endoscopy]. AB - Triple site biopsy specimens were taken from antrum, corpus, and supraangle simultaneously in 3002 Japanese cases to compare the differences among the biopsy sites for the evaluation of mucosal atrophy and inflammation. The prevalence of H. pylori infection was almost same in biopsy specimens from the different sites, but the detective rates for mucosal atrophy and intestinal metaplasia were remarkably higher in the supraangle. Our results indicate that the antral and the corpal biopsy are suitable for the evaluation of inflammation and H. pylori infection, but the supraangular biopsy is more reliable for the recognition of mucosal atrophy and intestinal metaplasia than the antral and the corpal biopsy. PMID- 11218395 TI - [Serological diagnosis of Helicobacter pylori infection]. AB - H. pylori gastritis elicits both a local and a systemic immune response. Although multiple invasive tests are available for the diagnosis of H. pylori infection, serum testing for anti-H. pylori antibodies is a minimally invasive test available to diagnose this infection. Latex agglutination is available, but most kits use ELISA. The sensitivities and specificities of many commercial kits were more than 90%. However, most of these serologic detection kits were made in Western countries. There might been the influence of geographical differences on test results. Recently, serological test has been reported about of usefulness in monitoring after eradication therapy at long-term period. PMID- 11218396 TI - [13C-urea breath test]. AB - A 13C-urea breath test(13C-UBT) is known to be a good diagnostic method for detecting H. pylori infection since it is non-invasive, simple and accurate. Its diagnostic capability in determining H. pylori eradication has been studied using 153 patients (who underwent the H. pylori eradication therapy) as subjects at two times: 6-8 weeks after the end of administration (at the time of determination of eradication) and 6 months afterwards. When determination was made, the sensitivity and specificity of 13C-UBT compared to culture and histology were 100% and 95.1%, respectively. Seven inconsistent cases were positive according to 13C-UBT and negative according to two other methods. After 6 months, both sensitivity and specificity were 100% and 4 of the 7 inconsistent cases became positive according to all three methods. These results indicate that the 13C-UBT is superior in terms of sensitivity and specificity to culture and histology and recognize the failure eradication earlier than ether two methods. Re-examination of inconsistent cases should be performed after 6 months. After covered by insurance, the H. pylori eradication therapy will become a general form of treatment of peptic ulcers. 13C-UBT in particular has proven most useful for diagnosis of eradication. PMID- 11218397 TI - [Rapid urease test]. AB - The rapid urease test is a simple, sensitive, and highly specific test that enables the endoscopist to diagnose Helicobacter pylori infection in the endoscopy room. Determination of the infection status of Helicobacter pylori by biopsies from the gastric body had a significantly higher sensitivity than antral biopsies. A false-negative reaction by rapid urease test occurred the use of antibiotics (correlates with clearance of the bacteria) and the use of proton pump inhibitor or a part of mucosal protective agents(correlates urease inhibitory effect) and in the case of non-urease producing Helicobacter pylori. The rapid urease test satisfactory overall sensitivity before eradication treatment. However, the sensitivity of these rapid urease tests was lower after eradication than before eradication. PMID- 11218398 TI - [Diagnosis of H. pylori infection by PCR]. AB - Because of its high sensitivity, polymerase chain reaction (PCR) method can be used to detect the presence of very few numbers of H. pylori organisms in gastric biopsy materials or gastric juice samples. PCR has also been applied to the detection of H. pylori organisms in the oral cavity, in stools, and in the environment. RT-PCR is useful to study the expression of H. pylori pathogenic genes and gene expression of gastric mucosal cells in response to H. pylori infection. Other PCR-based techniques, such as PCR-RFLP or real-time quantitative PCR, are now providing important information on H. pylori and pathophysiology of H. pylori infection. PMID- 11218399 TI - [Genetic diagnosis of H. pylori strains]. AB - Helicobacter pylori strains are divided into two broad families, type I and type II, based on whether or not they possess the cag pathogenicity island (cagPAI). It has been suggested that cagPAI is inherited by horizontal transfer from an unknown microorganism, and the genes of cag are thought to be encoded by a putative type IV secretory system. In addition, CagA may be delivered from attached H. pylori into the host crytoplasm by this system and is tyrosine phosphorylated in gastric epithelial cells. The phosphorylated CagA may play a crucial role in promoting the inflammatory responses of gastric mucosa. These findings suggest that type I H. pylori is a pathogenic H. pylori. PMID- 11218400 TI - [Antimicrobial resistant test of H. pylori]. AB - The resistance of Helicobacter pylori (H. pylori) to antibiotics leaves great influence on treatment outcome. Agar and broth dilution techniques are difficult to perform and not practical. E-test has the advantage of allowing visualization of resistant subpopulations of bacteria within zones of inhibitions. We studied point mutation of 23s-rRNA gene for H. pylori strains. (74 clarithromycin (CAM) resistant, 6 CAM-susceptible) The results of these assays were well correlated with these of E-test. The cure rate of triple therapy with metoronidazole (MTZ) for CAM-resistant H. pylori is 100%(11/11), and that with CAM for MTZ-resistant H. pylori is 94.4% (17/18). It is very difficult to eradicate CAM and MTZ resistant H. pylori. PMID- 11218401 TI - [Morphological investigation of H. pylori and its culture method]. AB - H. pylori plays important roles in the pathogenesis of active gastritis, peptic ulcer, and gastric cancer. Culture of H. pylori from suspicious materials is one of gold standard methods for the diagnosis of its infection. H. pylori has two types of morphological manifestation, spiral (mobile) and coccoid (immobile) forms. Morphological conversion from spiral to coccoid form and its reversion may be important role in its pathophysiology including bacterial properties, pathogenicity, and etiology. However, the mechanism and significance of such transformation of H. pylori have remained unknown. In this chapter, we introduce the conventional and new culture methods of H. pylori and review the current knowledge regarding both two types of morphological manifestation and pathophysiological significance of such transformation. PMID- 11218402 TI - [Indication of H. pylori eradication therapy--who should be treated?]. AB - With increased evidence of H. pylori infection being deeply related with various gastric diseases, its curative therapy will be approved by social security foundation soon also in Japan. Japanese Society of Helicobacter reported a guideline for H. pylori diagnosis and treatment in July 2000. In the guideline, only peptic ulcers and low grade MALT lymphomas are recommended as an indication of H. pylori eradication and other diseases such as atrophic gastritis, post EMR state for early gastric cancer and post-operated stomach due to gastric cancer, hyperplastic polyps and non-ulcer dyspepsia, were not included. It is speculated that while benefit of eradication therapy for peptic ulcers and low grade MALT lymphomas has been supported by much clinical evidence, that for other diseases was judged not to be enough. Especially as to atrophic gastritis, eradication therapy might be considered in aspect of decreasing gastric cancer risk in Japan. Since accumulated epidemiological and experimental data strongly support its positive correlation with cancer risk, patients in high risk group for gastric cancer could be included for a target eradication therapy. In present, indication of the therapy should be clinically and socially decided according to individual patient. PMID- 11218403 TI - [Selection of antibiotics and planning of eradication for H. pylori infection]. AB - There is general agreement that H. pylori should be eradicated in patients with peptic ulcers. But the optimal therapeutical regimen to be used still remains a matter for many investigations. An increase in the prevalence of antibiotic resistant H. pylori strains has been reported recently. The recommended drugs for the eradication in Japan are clarithromycin (CAM) and amoxicillin (AMPC) because metronidazole (MNZ) is anti-parasites drug in Japan. A total of 392 H. pylori strains in the last twelve years were tested for sensitivity to CAM, MNZ, and AMPC. The Primary resistance of H. pylori to CAM, MNZ, and AMPC were found in 10.2%, 26.5%, and 0.3% strains, respectively. The resistant strains to CAM were gradually increasing in the last few years. The eradication therapies which do not increase antibiotics resistant strains after eradication failure were reported. The recommendation for eradication in patients with peptic ulcer disease includes those with bleeding ulcers. The pretreatment with proton pump inhibitors (PPI) does not influence the success of PPI-based triple therapy in eradicating H. pylori. PMID- 11218404 TI - [Usefulness of new triple therapy containing PPI]. AB - The guideline on the management of H. pylori was developed by the Japanese Society for Helicobacter Research in 2000, and new triple therapy with lansoprazole, amoxicillin and clarithromycin is recommended. At first, we determined the eradication ratio and the frequency of adverse effects, considering difference of genetic polymorphism in metabolizing enzyme of PPI, CYP2C19. No significant difference was shown among the groups of different metabolizing activity in the two points of view. Next, resistance to antibiotics of H. pylori were determined in the eradication-failure cases and compared before and after the therapy. The result did not showed that strains newly acquired the resistance during the therapy. We emphasis that the new triple therapy can be performed without considering the genetic difference or antibacterial resistance until now and that we should examine how eradication is completely performed. PMID- 11218405 TI - [How and when should we check Helicobacter pylori infection after eradication therapy?]. AB - In Japan, The new triple therapy was opened for Helicobacter pylori (HP) eradication from Nov. 1, 2000. The Japanese Society for Helicobacter Research presented a guideline for HP eradication. It recommended that HP infection should be checked at least 4 weeks after the treatment for peptic ulcer and HP infection using HPIgG antibody, rapid urease test, urea breath test, histology and/or culture. However, it did not state the best way and suitable timing to check HP infection after the eradication therapy. In this study, we investigated the accuracy of PyloriTek test(a 1-h rapid urease test) and tried to establish the suitable timing for checking HP infection after eradication therapy. In conclusion, when patients are examined more than 4 months after eradication therapy, the use of PyloriTek alone may be sufficient for correctly diagnosing HP infection. PMID- 11218407 TI - [Anti-ulcer therapy after eradication of Helicobacter pylori]. AB - Helicobacter pylori (H. pylori) infection is the cause of the frequent relapse of peptic ulcer disease. Successful eradication therapy of H. pylori is associated with a decline in the recurrence of peptic ulcer. In this paper, we discussed the significance of anti-ulcer therapy after H. pylori eradication therapy. In patients with duodenal ulcer, maintenance therapy for preventing ulcer recurrence is not necessary because the rate of ulcer recurrence after eradication therapy is very low. However, in patients with gastric ulcer, the rate of ulcer relapse and reflux esophagitis ranges between 5-10% in the Japanese population even after successful eradication therapy; therefore, maintenance therapy for 1 year may be permissible in patients with gastric ulcer even after successful eradication therapy. PMID- 11218406 TI - [A strategy for second-line anti-Helicobacter pylori therapy in patients with previously failed treatment]. AB - Highly effective H. pylori eradication therapies are currently used in Japan. However, eradication failures still appear in a considerable proportion of cases. In such refractory cases, several second-line eradication therapies and therapeutic efficacies have been only exceptionally studied. Our aims were to analyze the reasons and evaluate the second-line therapies when first-line eradication therapies fail. We make a strategy for second-line anti-H. pylori therapy in patients with previously failed treatment. PMID- 11218408 TI - [Occurrence of upper gastrointestinal tract disease after Helicobacter pylori eradication]. AB - Helicobacter pylori (H. pylori) infection is recognized to be a pathogen of various gastro-duodenal disease. Eradication therapy of H. pylori reduces the recurrence of gastro-duodenal ulcer, improves gastritis histologicaly, and is suggested to act an certain role in protection against gastric carcinogenesis. Although, several studies show uncomfortable results arise after H. pylori infection was cured. These studies suggest that gastro-esophageal reflux disease (GERD) and gastro-doudenal erosion may increase after successful eradication of H. pylori. Recently, adenocarcinoma of the gastric cardia and esophagus increase in incidence. Reflux esophagitis and Barrett's esophagus are recognized as precancerous lesion of esophageal adenocarcinoma. It is uncertain the association of newly occurrence of GERD after H. pylori eradication and increase of esophageal adenocarcinoma. Although GERD may lead to adenocarcinoma, long term observations is necessary after H. pylori eradication. PMID- 11218409 TI - [Epidemiology and clinical role of childhood Helicobacter pylori infection]. AB - Colonization of Helicobacter pylori depends on virulence factors of the organism, host factors and environmental factors. The prevalence of H. pylori differs between developing and Western developed countries, suggesting that the socioeconomic status influences the acquisition of the infection. The prevalence of Japanese children has been almost equal to that of Western countries. Although a main mode of transmission remains unclear, childhood is critical for acquisition of the infection. H. pylori causes gastritis (especially nodular gastritis) and duodenal ulcers in children but rarely gastric ulcers. No pediatric cases with H. pylori-associated gastric cancer have been reported. However, precancerous lesions including mucosal atrophy can develop in the infected children. Further studies in children are needed on strategy for H. pylori infection including prophylaxis of gastric cancer. PMID- 11218410 TI - [Gastric mucosal immunity induced by H. pylori infection]. AB - H. pylori infection induces various humoral and cellular immunities in gastric mucosa. Some reports indicate predominant CD4+ cells infiltrate in H. pylori infected gastric mucosa, and these cells express the T helper 1 phenotype. Local humoral immunity is also induced. Gastric plasma cells produce anti-H. pylori antibodies, however, their protective immunity is not enough to eradicate bacteria in human. We found heat shock protein 60 kDa (hsp60) may be closely associated with pathogenesis in MALT lymphoma. IgG1 antibodies to hsp60 were significantly correlated with the antibodies to H. pylori whole cell in patients with MALT lymphoma. CD40-CD40L dependent B cell proliferation was induced by cytokine and/or hsp60 stimulations in those patients. Cytotoxicity of gastric epithelial cells which is associated with host immunity induced by H. pylori infection is still unclear. We found that lymphocytes from patients with peptic ulcer showed cytotoxicity to gastric cell line HGC-27 in vitro. Cytotoxicity was enhanced by cytokine stimulus to T-lymphocytes and by heat stress and/or patients' antibodies treatment of HGC-27 cells. The pathogenicity of H. pylori may involve not only bacterial virulence factor but also host immunity. Studies of mucosal local immunity will help explain the mechanisms of H. pylori induced gastrodoudenal diseases. PMID- 11218411 TI - [The role of Helicobacter pylori infection and effect of eradication in experimental animal models of gastric carcinogenesis]. AB - Helicobacter pylori (Hp) was concluded to be 'a definite carcinogen' by WHO/IARC in 1994. We have demonstrated that Hp infection enhances chemical carcinogen induced stomach carcinogenesis in Mongolian gerbils (MGs) using N-methyl-N'-nitro N-nitrosoguanidine or N-methyl-N-nitrosourea. Not only well-differentiated but also poorly differentiated and signet ring cell types of cancers are observed, mimicking the human case. Eradication of Hp was found to be effective of preventing enhancing effects. Hp infection alone, without chemical carcinogens, caused submucosal proliferating lesions, but not gastric carcinomas, in contrast to reports that Hp infection alone may act on a complete carcinogen. Precise pathological assessment is required to solve this controversy. Here we demonstrate alleviation of Hp induced gastric lesions with eradication in MGs. PMID- 11218412 TI - [Treatment of gastric MALT lymphoma by H. pylori eradication]. AB - Strong evidence exists for the efficacy of H. pylori eradication in achieving gastric low-grade MALT lymphoma (L-MALT) regression when the bacteria present. Besides histological evaluation, the appearance of endoscopic finding such as 'discolored mucosa-like atrophy' after treatment may be useful for the prediction of its outcome (endoscopic evaluation). However, a reliable marker for molecular evaluation is not obtained so far. On the other hand, long-term control of L-MALT with H. pylori eradication therapy is uncertain and there still remains a subset of patients with no evidence of H. pylori or who fail H. pylori eradication therapy. Therefore, the optimal non antibiotic therapy for these patients has been studied. According to the recent report, radiation therapy appears to be well tolerated and effective for patients with gastric L-MALT. PMID- 11218413 TI - [Intestinal metaplasia and Helicobacter pylori infection, their relationship and effects of eradication therapy]. AB - Intestinal metaplasia is characterized by Goblet cells and Peneth cells in histological examination. It is frequently observed in gastric mucosa with atrophic gastritis and easily diagnosed using Methylene blue stain in endoscopy. Intestinal metaplasia is seemed to occur during the progression of atrophic gastritis. From our prospective endoscopic follow-up study over 8 years, progression of intestinal metaplasia in gastric body is observed in 44.4% out of 27 H. pylori positive patients. Progression of atrophy is also observed in 37.0% of cases. Development of intestinal metaplasia is also assured in other clinical investigations and experimental studies using Mongolian Gerbils. However, reversibility of intestinal metaplasia after H. pylori eradication is under discussion still now. In our study, we can not observe the regression of intestinal metaplasia even 2 years after successful H. pylori eradication. PMID- 11218415 TI - [The perspectives of upper GI tract diseases]. AB - Recently, most of the upper GI tract diseases, peptic ulcer, chronic gastritis, gastric cancer as well as MALT lymphoma, have been explained by the infection of Helicobacter pylori (H. pylori). However, it is not evident whether or not gastric cancer is induced solely by the bacterial infection at this stage. On the other hand, it is reported that the eradication of H. pylori might evoke the reflux esophagitis as well as esophageal and fundic cancer. These important issues remain to be elucidated for the investigation of upper GI tract in the 21st century. The development of new endoscopic technology may be another promising field of upper GI tract. PMID- 11218414 TI - [Mechanism of drug resistance in Helicobacter pylori]. AB - Clarithromycin is one of the most important antibiotics for H. pylori eradication. However, 5-10% was reported to be resistant. It has been shown that one point mutation in the 23S rRNA gene is associated with resistance to clarithromycin. To detect H. pylori infection and the mutation simultaneously, we have designed PCR primers specific for H. pylori, and established assays of PCR RFLP and PCR-preferential homo-duplex formation (PHFA). Using this assay, we can detect mixed infections with wild and mutant-strains. The prevalence of mutant infection increased through clarithromycin-based eradication. However, the existence of mutant strains had been confirmed before therapy in most cases who 'converted' to mutant after therapy. Metronidazole is also one of the most important antibiotics for eradication. However, 5-50% was reported to be resistant. It has been shown that rdx gene mutation is associated with resistance. It is reported that inactivation of the rdx gene is frequently, but not always, associated with resistance to metronidazole. Amoxicillin resistant strains were rare (1.2% in Japanese strains). It is reported that penicillin binding protein might play a role in the resistance. By detecting of the resistance based on the molecular mechanism, patients can be treated with adequate antibiotics with information about resistance. PMID- 11218416 TI - [The Cochrane Collaboration: the present and the future]. AB - The Cochrane Collaboration has developed in response to the call for systematic, up-to-date reviews of all relevant randomized controlled trials (RCTs) of health care. Both evidence-based medicine (EBM) and the Cochrane Collaboration have been gaining attention of healthcare professionals in Japan recently. Ways for Japanese people to contribute to the Cochrane Collaboration are as follows: participating in a collaborative review group as a reviewer; increasing registry number of Japanese RCT articles; and Japanese translation of their outputs and its dissemination. Establishment of Japan Cochrane Center will integrate and promote the related activities. Furthermore, the positive recognitions for the Cochrane Collaboration and EBM among Japanese people can improve environments for conducting clinical trials and epidemiological studies in Japan. PMID- 11218417 TI - Demonstrating effectiveness of passive radon-resistant new construction. AB - Fifty percent of homes tested for radon in Rock Island County, IL, have radon levels above the U.S. Environmental Protection Agency (EPA) action guideline of 4 picoCuries per liter (pCi/L) of air. Therefore, the county is classified by the EPA as Zone 1 on the EPA's Map of Radon Potential. Radon-resistant new construction (RRNC) strategies for new homes are recommended by the EPA in Zone 1 areas. One city in the county, East Moline, reduced the cost of building permits for contractors volunteering to build new homes incorporating modified passive RRNC. Forty-six of 124 new homes built with passive RRNC in the city were tested during this study. Only 27 of the homes tested were below 4-pCi/L, justifying the importance of testing the system to ensure levels are below the action guideline. To provide additional support to an argument in favor of changing city building codes to the required RRNC, 23 of the homes were also tested with the systems deactivated. After systems were deactivated, 73% of the homes had radon levels above the action guideline. Four homes were sampled for bioaerosols to evaluate if passive RRNC might impact other indicators of poor indoor air quality (IAQ). The results of the research will be discussed here. PMID- 11218418 TI - Comparison of real-time instruments used to monitor airborne particulate matter. AB - Measurements collected using five real-time continuous airborne particle monitors were compared to measurements made using reference filter-based samplers at Bakersfield, CA, between December 2, 1998, and January 31, 1999. The purpose of this analysis was to evaluate the suitability of each instrument for use in a real-time continuous monitoring network designed to measure the mass of airborne particles with an aerodynamic diam less than 2.5 microns (PM2.5) under wintertime conditions in the southern San Joaquin Valley. Measurements of airborne particulate mass made with a beta attenuation monitor (BAM), an integrating nephelometer, and a continuous aerosol mass monitor (CAMM) were found to correlate well with reference measurements made with a filter-based sampler. A Dusttrak aerosol sampler overestimated airborne particle concentrations by a factor of approximately 3 throughout the study. Measurements of airborne particulate matter made with a tapered element oscillating microbalance (TEOM) were found to be lower than the reference filter-based measurements by an amount approximately equal to the concentration of NH4NO3 observed to be present in the airborne particles. The performance of the Dusttrak sampler and the integrating nephelometer was affected by the size distribution of airborne particulate matter. The performance of the BAM, the integrating nephelometer, the CAMM, the Dusttrak sampler, and the TEOM was not strongly affected by temperature, relative humidity, wind speed, or wind direction within the range of conditions encountered in the current study. Based on instrument performance, the BAM, the integrating nephelometer, and the CAMM appear to be suitable candidates for deployment in a real-time continuous PM2.5 monitoring network in central California for the range of winter conditions and aerosol composition encountered during the study. PMID- 11218419 TI - Oxidation of gas mixtures containing dimethyl sulfide, hydrogen sulfide, and methanethiol using a two-stage biotrickling filter. AB - A biofiltration technique was developed for removing a mixture of hydrogen sulfide (H2S), methanethiol (MeSH), and dimethyl sulfide (Me2S) from waste gases. Since H2S, especially at high concentrations, disturbs the removal of Me2S, two biotrickling filters with different microbes and operating pH levels were connected in series to create a two-stage system. Different loads of these gases were studied in order to determine their impact on the removal capacity of the system. The microbial consortia for these filters were enriched from the sludge of a Finnish refinery with bubbling H2S or Me2S. Acclimation for Me2S took 2 weeks, though no acclimation time was needed for the other gases. The first filter, at a pH of 2, removed most of the H2S and some of the MeSH and Me2S. The second filter, at a pH of approximately 6.5, removed the rest of the MeSH and most of the Me2S. The total maximum loads of the whole two-stage biotrickling filter were 1150 g/m3/day for H2S-S (suffix S indicates the results are counted as sulfur amounts), 879 g/m3/day for Me2S-S, and 66 g/m3/day for MeSH-S treated in a gas mixture. The average removal efficiencies for all gases tested were 99% or higher. PMID- 11218420 TI - Observations and model simulations of carbon monoxide emission factors from a California highway. AB - A series of twelve intensively monitored 1-hr CO dispersion studies were conducted near Davis, CA, in winter 1996. The experimental equipment included twelve CO sampling ports at elevations up to 50 m, three sonic anemometers, a tethersonde station, aircraft measurements of wind and temperature profile aloft, and a variety of conventional meteorological equipment. The study was designed to explore the role of vehicular exhaust buoyancy during worst-case meteorological conditions, such as low winds oriented in near-parallel alignment with the road during a surface-based nocturnal inversion. From the study, field estimates of the CO emission factor (EF) from a California vehicle fleet were computed using two different methods. The analysis suggests that the CT-EMFAC/EMFAC (EMission FACtor) models currently used to conduct federal conformity modeling significantly overpredict CO emissions for high-speed, free-flowing traffic on California highways. PMID- 11218421 TI - Personal exposure levels and microenvironmental concentrations of formaldehyde and acetaldehyde in the Helsinki metropolitan area, Finland. AB - Personal 48-hr exposures to formaldehyde and acetaldehyde of 15 randomly selected participants were measured during the summer/autumn of 1997 using Sep-Pak DNPH Silica cartridges as a part of the EXPOLIS study in Helsinki, Finland. In addition to personal exposures, simultaneous measurements of microenvironmental concentrations were conducted at each participant's residence (indoor and outdoor) and workplace. Mean personal exposure levels were 21.4 ppb for formaldehyde and 7.9 ppb for acetaldehyde. Personal exposures were systematically lower than indoor residential concentrations for both compounds, and ambient air concentrations were lower than both indoor residential concentrations and personal exposure levels. Mean workplace concentrations of both compounds were lower than mean indoor residential concentrations. Correlation between personal exposures and indoor residential concentrations was statistically significant for both compounds. This indicated that indoor residential concentrations of formaldehyde and acetaldehyde are a better estimate of personal exposures than are concentrations in ambient air. In addition, a time-weighted exposure model did not improve the estimation of personal exposures above that obtained using indoor residential concentrations as a surrogate for personal exposures. Correlation between formaldehyde and acetaldehyde was statistically significant in outdoor microenvironments, suggesting that both compounds have similar sources and sinks in ambient urban air. PMID- 11218422 TI - Semi-volatile species in PM2.5: comparison of integrated and continuous samplers for PM2.5 research or monitoring. AB - Fine particles in urban atmospheres contain substantial quantities of semi volatile material [e.g., NH4NO3 and semi-volatile organic compounds (SVOCs)] that are lost from particles during collection on a filter. Several diffusion denuder samplers have been developed for the determination of both NO3- and organic semi volatile fine particulate components. The combination of technology used in the BOSS diffusion denuder sampler and the Harvard particle concentrator has resulted in the Particle Concentrator-Brigham Young University Organic Sampling System (PC BOSS) for the 24-hr (or less) integrated collection of PM2.5, including NH4NO3 and semi-volatile organic material. Modification of the BOSS sampler allows for the weekly determination of these same species. Combination of BOSS denuder and tapered element oscillating microbalance (TEOM) monitor technology has resulted in the real-time ambient mass sampler (RAMS) for the continuous measurement of PM2.5, including the semi-volatile components. Comparison of the results obtained with the BOSS and with each of the newly developed modifications of the BOSS indicates that the modified versions can be used for the continuous, daily, or weekly monitoring of PM2.5, including semi-volatile species, as appropriate to the design of each sampler. PMID- 11218423 TI - Assessment of opacimeter calibration according to International Standard Organization 10155. AB - This paper compares the calibration method for opacimeters issued by the International Standard Organization (ISO) 10155 with the manual reference method for determination of dust content in stack gases. ISO 10155 requires at least nine operational measurements, corresponding to three operational measurements per each dust emission range within the stack. The procedure is assessed by comparison with previous calibration methods for opacimeters using only two operational measurements from a set of measurements made at stacks from pulp mills. The results show that even if the international standard for opacimeter calibration requires that the calibration curve is to be obtained using 3 x 3 points, a calibration curve derived using 3 points could be, at times, acceptable in statistical terms, provided that the amplitude of individual measurements is low. PMID- 11218424 TI - An assessment of the impact of California's Phase 2 Reformulated Gasoline on ozone air quality. AB - California's Phase 2 Reformulated Gasoline (CaRFG), introduced early in 1996, represents an important step toward attainment of ozone standards. Studies of vehicle emissions and ambient air quality data have reported substantial reductions of ozone precursors due to CaRFG. This study uses daily measurements of regional ozone and meteorology to estimate the effect of CaRFG on ozone concentrations in three areas of California. In each area, a regression model was used to partially account for the daily effects of meteorology on area-wide ozone maxima for May-October. The statistical models are based on combinations of air temperature aloft (approximately 5000 ft), surface air temperatures, and surface wind speeds. Estimated ozone benefits were attributed to CaRFG after accounting for meteorology, which improved the precision of the estimates by approximately 37-57% based on a resampling analysis. The ozone benefits were calculated as the difference in ozone times the proportion of the reductions of hydrocarbons and nitrogen oxides attributed to CaRFG by the best available emission inventories. Ozone benefits attributed to CaRFG (with approximately 90% confidence) are 8-13% in the Los Angeles area, -2-6% in the San Francisco Bay area overall with greater benefits in two major subregions, and 3-15% in the Sacramento area. PMID- 11218425 TI - Theory and laboratory study of a tall passive chamber for measuring gas fluxes at soil surface. AB - A tall passive flux chamber with a height significantly greater than its horizontal dimensions is proposed for measuring fluxes of volatile organic compounds (VOCs) at the soil surface. The main feature of this tall chamber is the presence of a vertical concentration gradient of the target gas in the chamber. The emission and transport behavior of the target gas in the soil chamber system are analyzed using the diffusion theory. A mathematical model is developed to estimate the flux from the soil into the tall chamber, providing the target gas establishes a detectable vertical concentration gradient in the chamber. To obtain the data required for calculating flux, only two gas concentrations (C1 and C2) at two heights (h1 and h2) within the chamber need to be measured at the end of a short chamber placement time (tp). To evaluate the applicability of the tall chamber for measuring flux, several laboratory tests have been conducted, using CH2Cl2 and CH3Br as the target gases. The results indicate that the proposed tall chamber has promising potential as a method for measuring fluxes of VOCs at the soil surface. PMID- 11218426 TI - The MMT bag for emission source sampling: design and evaluation. AB - This paper presents the design and evaluation results for a metal-coated multilayer Tedlar (MMT) bag that was developed for the collection of source emissions. The applicability of the MMT bag was evaluated for a number of important greenhouse relevant gases: CO, CO2, CH4, N2O, and total hydrocarbons (THCs). The bag was tested for durability and stability for a range of concentrations of the tested compounds using both laboratory-prepared samples and real source samples. The results show that all tested compounds were more stable when stored in the MMT bag than when stored in a regular Tedlar bag. These compounds can be stored at room temperature for at least 3 months without significant changes in concentration. When properly packed, the MMT bag is durable and may be shipped by air. The MMT bag is lower in cost, lighter in weight, and easier to clean, and it requires less devices during the subsequent laboratory analysis compared with a stainless steel canister, which is often used to collect air and source samples. PMID- 11218427 TI - Analysis of moisture findings in the interior spaces of Finnish housing stock. AB - A grading system was developed to rate the moisture damage profile of dwellings and to study the relationship between moisture-induced indoor air problems and occupant health. A total of 630 randomly selected houses and apartments, built between 1950 and 1989, were visually inspected. Moisture observations were standardized into three damage levels. Thus, a system to classify the homes into three grades was devised. The two grades of homes associated with the highest levels of damage were graded as index homes. Overall, 51% of the sample had some kind of moisture fault in them and one in every three homes (33%) was classified as an index home. The mean number of damage incidents in the index dwellings varied from 1.4 to 2.6. The mean number of damage incidents in the reference homes was 0.28. Prevalence of index dwellings was significantly higher (p < 0.01) in houses (38%) than in apartments (26%). There was no major difference in the prevalence of index buildings in houses built in any particular decade (30-35%). Moisture was observed in 28% of bathrooms, in 10% of kitchens, and in 17% of other spaces. Indoor relative humidity (RH) levels were low in most homes. PMID- 11218428 TI - A procedure for use in estimating human exposure to particulate matter of ambient origin. AB - Modern epidemiology has shown that fluctuations of mortality data are statistically significantly correlated with fluctuations of ambient particulate matter (PM) concentration data. This relation cannot be confounded by exposure to PM of indoor origin because the concentrations of ambient PM are not correlated with concentrations of PM of indoor origin. It has been suggested, given the above understanding, that modern PM exposure measurements and analysis should create separate estimates of exposure to all PM of ambient origin and exposure to all PM of nonambient origin (primarily of indoor origin), and not exposure to total PM. This paper reviews the developments of the form of the general microenvironmental mass balance equation that can be utilized for estimating human exposure to PM of ambient origin and for estimating the portion of total PM exposure that is attributable to nonambient origin PM. The equation is perfectly general and can be applied to conditions of time-varying factors that influence exposure, such as rapidly changing air-exchange rates in a home as doors and windows are opened and closed, and turning on and off air cleaners in a home. It is suggested that this procedure be applied in exposure assessment studies and validated using independent techniques of estimating exposure to PM of ambient origin available in the literature. PMID- 11218430 TI - Forecasting generation of urban solid waste in developing countries--a case study in Mexico. AB - Based on a study of the composition of urban solid waste (USW) and of socioeconomic variables in Morelia, Mexico, generation rates were estimated. In addition, the generation of residential solid waste (RSW) and nonresidential solid waste (NRSW) was forecasted by means of a multiple linear regression (MLR) analysis. For residential sources, the independent variables analyzed were monthly wages, persons per dwelling, age, and educational level of the heads of the household. For nonresidential sources, variables analyzed were number of employees, area of facilities, number of working days, and working hours per day. The forecasted values for residential waste were similar to those observed. This approach may be applied to areas in which available data are scarce, and in which there is an urgent need for the planning of adequate management of USW. PMID- 11218429 TI - Development and performance of an alternative biofilter system. AB - Step tracer tests were carried out on lab-scale biofilters to determine the residence time distributions (RTDs) of gases passing through two types of biofilters: a standard biofilter with vertical gas flow and a modified biofilter with horizontal gas flow. Results were used to define the flow patterns in the reactors. "Non-ideal flow" indicates that the flow reactors did not behave like either type of ideal reactor: the perfectly stirred reactor [often called a "continuously stirred tank reactor" (CSTR)] or the plug-flow reactor. The horizontal biofilter with back-mixing was able to accommodate a shorter residence time without the usual requirement of greater biofilter surface area for increased biofiltration efficiency. Experimental results indicated that the first bed of the modified biofilter behaved like two CSTRs in series, while the second bed may be represented by two or three CSTRs in series. Because of the flow baffles used in the horizontal biofilter system, its performance was more similar to completely mixed systems, and hence, it could not be modeled as a plug-flow reactor. For the standard biofilter, the number of CSTRs was found to be between 2 and 9 depending on the airflow rate. In terms of NH3 removal efficiency and elimination capacity, the standard biofilter was not as good as the modified system; moreover, the second bed of the modified biofilter exhibited greater removal efficiency than the first bed. The elimination rate increased as biofilter load increased. An opposite trend was exhibited with respect to removal efficiency. PMID- 11218431 TI - Measurements of sulfur dioxide and formaldehyde in Taipei using a differential optical absorption spectrometer. AB - Taipei, the capital city of Taiwan, lies in a basin, and its topography prevents the dispersion of pollutants in the city. As a continuation of our air quality study, from February 1999 through June 1999, we measured the concentrations of SO2 at six different locations and of formaldehyde at five locations using a differential optical absorption spectrometer (DOAS). The average concentration of SO2 varied from 3.5 to 6.6 ppb. The average concentration was highest at Toucheng because of its proximity to point sources. The level in Hsientien was close to that in Toucheng, with Hsinyu showing the lowest concentrations. The DOAS and the Taiwan Air Quality Monitoring Network (TAQMN) measurements for SO2 were highly correlated (r2 > 0.9) for Toucheng, Panchiao, and Hsientien. However, DOAS SO2 concentrations were 2 times higher for Hsientien and slightly lower for Panchiao than the TAQMN concentrations were. The average concentration of formaldehyde varied from 7 to 10 ppb. Diurnal variation of formaldehyde closely followed the variation of ozone, especially when the 1-hr peak ozone concentration was > 60 ppb. Photochemical formation accounted for the ambient levels of formaldehyde in Taipei. Concentration of formaldehyde became significant on days when O3 concentration was high. Our results indicate that DOAS can replace conventional measurement techniques. PMID- 11218432 TI - The early management of the burn wound and observations on hypertrophic scarring. With special reference to the deep dermal level and hypertrophic scarring. AB - Much confusion about the management of the burn wound still exists in many a clinician's mind. This is an attempt to clarify the problem and create a better understanding of the importance of assessing the various depths of penetration of the thermal agent. The treatment varies from the use of minimal bland dressings left undisturbed to aggressive early tangential excision and skin grafting. This is discussed together with the rationale for this approach and some problems associated with it. A 'critical depth' of penetration at the deep dermal level, which spares the acini of the sweat glands, is suggested as the factor initiating later development of hypertrophic scarring. This can be prevented by early excision and skin grafting. PMID- 11218433 TI - Post-decompression gallbladder haemorrhage in obstructive jaundice. A report of 2 cases. AB - Two cases of massive haemorrhage from the gallbladder in patients suffering from common bile duct obstruction are described. Sudden operative decompression of the massively distended gallbladder was the probable cause of the bleeding. PMID- 11218434 TI - Uterine actinomycosis associated with an enterocutaneous fistula. A case report. AB - A postmenopausal woman with suppurative actinomycotic uterine infection complicated by an enterocutaneous fistula is reported. It occurred against a background of prolonged use of an intra-uterine contraceptive device. PMID- 11218435 TI - Abdominal tuberculosis. A report of 3 cases. AB - Three patients admitted to the surgical wards of Johannesburg Hospital in whom abdominal tuberculosis was suspected are presented. In every case difficulties were encountered in diagnosis and treatment. Each case presentation is followed by a short commentary on relevant aspects of abdominal tuberculosis. PMID- 11218436 TI - Candidiasis in an intensive care unit. PMID- 11218437 TI - GP anaesthetists. PMID- 11218438 TI - Do abnormal hemipelvic bone stresses contribute to loosening and migration of screw-threaded cups? AB - Excellent long-term results have been reported with the Charnley low-friction arthroplasty. Failure of the cemented acetabular component has been identified as a problem in the longer term, while cemented hip replacements in active young patients have exhibited a disconcerting incidence of early clinical or radiological failure. This resulted in the development of the cementless arthroplasty. Bone responds favourably to an optimal stress window and reacts dynamically to metal implants that have a greatly differing modulus of elasticity. This study represents a comparative qualitative analysis of the peri acetabular hemipelvic stresses after loading two cementless (press-fit and screw threaded) acetabular components inserted into identical bone models. A simplified model of the artificial hip joint was constructed and the very sensitive stress analysis technique of holographic interferometry was used for the investigation. Peri-acetabular stress concentrations were noted with the screw-threaded cup. This may predispose to bone resorption and it is suggested that these could be implicated in the migration of these cups described in published reports. PMID- 11218439 TI - Humidification in intensive care. AB - The normal physiological function of the upper respiratory tract is to filter and humidify inspired air. In intensive care units the upper respiratory tract is frequently bypassed. The importance of humidifying and warming the dry, cold, piped gas is well documented. The results of lack of adequate humidification include endotracheal tube obstruction, impairment of the mucociliary elevator and altered pulmonary function. Optimal levels of humidification are as yet undefined and useful clinical markers of adequate humidification are not available. As a result there is a bewildering array of humidification devices available at present, the most recent of which are heat and moisture exchangers with or without specific filtration properties. This article reviews available data on these humidification devices, and recommends an approach to their appropriate use, based on the probable physiological needs of individual patients. PMID- 11218440 TI - Tension pneumoperitoneum aggravating respiratory failure. A case report. AB - A case of tension pneumoperitoneum secondary to barotrauma is reported. Any patient needing high pressures for ventilation and oxygenation is prone to this complication. The important respiratory and haemodynamic implications are discussed. It is suggested that drainage of a tension pneumoperitoneum is easy and safe and has major beneficial effects on the respiratory and cardiovascular systems. PMID- 11218441 TI - Esmolol in a case of severe tetanus. Adequate haemodynamic control achieved despite markedly elevated catecholamine levels. AB - A patient with severe tetanus, who had a sympathetic crisis while sedated with 30 mg/h diazepam and 30 mg/h morphine, is described. Satisfactory control of the haemodynamic crisis was achieved with bolus doses of esmolol to a total of 180 mg. A disturbing finding was that although there was adequate control of the tachycardia and hypertension, arterial catecholamine levels remained markedly elevated. Adrenaline levels of 531 pg/ml (normal 10-110 pg/ml) and noradrenaline levels of 1,036 pg/ml (normal 100-500 pg/ml) were recorded when the patient had a systolic arterial pressure of 110 mmHg and a heart rate of 97/min. The implications of this finding are discussed. PMID- 11218442 TI - The Department of Surgery, Baragwanath Hospital--the early days. PMID- 11218443 TI - Traumatic haemothorax--experience of a protocol for rapid turnover in 1,845 cases. AB - Incomplete or prolonged drainage of the pleural cavity for haemothorax may lead to the development of empyema, with long-term morbidity. Using a protocol based on vigorous physiotherapy and early withdrawal of the thoracostomy tube (average drainage time 27.1 hours), hospital stay in 1,845 patients with traumatic haemothorax was 48 hours or less in 81.8% of patients. In all, 152 haemothorax patients (8.1%) required either early or late thoracotomy, 46 of which were for associated cardiac injury. Prophylactic antibiotics were not given routinely. Severe complications occurred in 40 patients (2.2%); 15 developed empyema (0.8%) and 25 died (1.4%), mainly from ongoing haemorrhage. The early identification of patients needing operative or other intervention minimises the hospital stay and complications associated with residual blood in the pleural cavity. This study shows that the short-period drainage protocol used gives very acceptable results in the treatment of traumatic haemothorax. PMID- 11218445 TI - Forensic dentistry: a process of elimination. PMID- 11218444 TI - Carcinoma of the head of the pancreas. Morbidity and mortality of surgical procedures. AB - This retrospective study analyses the peri-operative morbidity and mortality of 165 patients presenting with carcinoma of the head of the pancreas over a 5-year period. Patients clinically fit for surgery (84%) were subdivided into three main groups, namely: group I (6%) underwent pancreaticoduodenal resection; group II (42%) had locoregionally advanced disease; and group III (36%) with metastatic disease. The latter group was subdivided into groups IIIa (22%) without ascites and IIIb (14%) with ascites. In the palliative groups (II and III), 61% underwent operative biliary drainage procedures, 33% a combined biliary drainage and a duodenal bypass procedure and 5% a duodenal bypass only. Obstructive jaundice recurred in 3% of cases after operative biliary drainage. Only 7% of patients required a duodenal bypass during follow-up. The mortality rates after surgery were 22% following pancreaticoduodenectomy (group I), 1.5% for the palliative procedures in group II, but 17% in group IIIa patients with metastatic disease without ascites and 83% when ascites was present (group IIIb). This study demonstrates that patients with ascites, although clinically fit for surgery, had a prohibitively high operative mortality rate and represented a subgroup of patients better treated by non-operative methods. Surgical drainage of the biliary system in all other cases had acceptably low morbidity and mortality rates. A prophylactic duodenal bypass is not mandatory. PMID- 11218446 TI - Dental infection control at the year 2000. Accomplishment recognized. AB - OVERVIEW: Health care providers have strived to address the many elements necessary to achieve effective infection control. Historical progress in microbiology and hospital asepsis provided the foundation for advances in dental preventive practices. Evidence supporting the application of current practices includes a long history of scientific and clinical investigations, technological advances in equipment and materials, and periodic publication of updated recommendations by professional health care organizations. CLINICAL IMPLICATIONS: The routine application of precautions such as multiple aseptic procedures, latex gloves, masks, protective eyewear, clinic coats, automated instrument decontamination devices, time-efficient heat sterilization modalities, chemical disinfectants, waste management procedures and single-use disposable items have created a safer environment for dental personnel and patients alike. PMID- 11218447 TI - 10 steps to shape your future. PMID- 11218448 TI - Rx to adjust to change. PMID- 11218449 TI - Chips. PMID- 11218450 TI - Corporate dentistry--a 2020 vision. PMID- 11218451 TI - Antimycotic agents in oral candidosis: an overview: 2. Treatment of oral candidosis. AB - As both humans and fungi are eukaryotic organisms, antifungal agents affect their cellular metabolism. Thus, a relatively few antifungals with minimal toxicity and side-effects are available compared with a plethora of antibacterials. These agents currently prescribed in dentistry belong to two major groups, the polyenes (nystatin and amphotericin B) and the azoles (imidazoles and triazoles). A newly recognized phenomenon known as the post-antifungal effect implies that antifungals, even at sub-therapeutic concentrations, may suppress the virulent attributes of yeasts, especially intra-orally where topical drug levels fluctuate dramatically during dosing intervals. PMID- 11218452 TI - Investigation and treatment of patients with teeth affected by tooth substance loss: a review. AB - Tooth substance loss, an increasing problem, may result from erosion, abrasion and attrition, often with more than one of these acting together. Investigation requires a detailed history and examination. The aim of treatment may be prevention of further damage in less affected cases. The treatment of severe tooth substance loss may be complex, especially in view of the reduced amounts of tooth substance which may be available and the need to find space because of the compensatory over-eruption of worn teeth. PMID- 11218453 TI - A synopsis of the adult dental health survey: oral health in the United Kingdom 1998. PMID- 11218454 TI - Extensive temporal bone pneumatization: incidental finding in a patient with TMJ dysfunction. AB - An 18-year-old male presented with symptoms of temporomandibular joint dysfunction. A panoramic radiograph revealed slight erosion of the condylar heads, and an incidental finding of multilocular radiolucencies in the zygomatic processes of the right and left temporal bones. CT scans were undertaken to exclude any sinister cause. The radiolucencies were shown to be extensive bilateral pneumatization of the temporal bones. Conservative management relieved the symptoms of TMJ dysfunction. PMID- 11218455 TI - Oral midazolam for adults with learning disabilities. AB - This paper demonstrates how oral midazolam can be employed as an alternative method of behaviour management to general anaesthesia for the dental treatment of people with learning disabilities. A range of treatments, from scaling to root canal therapy, can be carried out successfully using the sedation technique outlined. The advantages of sedation include reduced morbidity and mortality. Treatment outcomes are also likely to be improved as root canal therapy and periodontal care can be carried out over a number of visits rather than a single treatment session under general anaesthesia. Oral sedation with midazolam should improve the scope of dental treatment available to patients with disabilities. PMID- 11218456 TI - Enamel microabrasion. AB - A significant number of patients complain of discoloured teeth. The enamel microabrasion technique described in this article is a simple conservative method for improving the appearance of discoloured enamel. PMID- 11218457 TI - The use of hypnosis in dentistry: a review. AB - Hypnosis is a valuable technique in patient management. With appropriate training, general dental practitioners can widen the treatment options they can offer to patients, especially those who are dentally anxious. This article provides a brief theoretical and historical overview, and a review of the literature pertaining to the clinical uses of hypnosis in dentistry. PMID- 11218458 TI - First response. PMID- 11218459 TI - Walmsley's Web Watch. PMID- 11218460 TI - Sex and dentistry. PMID- 11218461 TI - The Lifelong Learning Scheme. PMID- 11218462 TI - Immediate anterior tooth replacement using fibre-reinforced composite. AB - The loss of anterior teeth can be psychologically and socially damaging to the patient the trauma of which can be minimized by immediate replacement of the teeth, preferably using a fixed prosthesis. This paper describes the immediate replacement of a lateral incisor using a fibre-reinforced composite with the natural tooth as the pontic. The abutment teeth can be conserved with minimal or no preparation, thus keeping the technique reversible, and can be completed at the chairside thereby avoiding laboratory costs. It can be used as an interim measure or as a definitive prosthesis. The advantages of this technique over other methods are also discussed. PMID- 11218464 TI - Periodontal splinting in general dental practice. AB - Splinting periodontally involved teeth is a technique that has been in use for centuries. This article gives a brief history and review of the literature concerning periodontal splinting and outlines the rationale and indications for the correct application of periodontal splinting in modern dental practice. The common types of splint and clinical techniques involved are described, addressing some of the clinical problems. PMID- 11218463 TI - Dentine caries: take it or leave it? AB - In modern dentistry the primary aim when excavating carious dentine is to eradicate only the highly infected, irreversibly demineralized and denatured biomass in order to allow effective restoration of the cavity, restoration of the surface anatomy of the tooth and to prevent disease progression. However, the boundary between this superficial zone of dentine requiring excavation and the deeper, affected but repairable tissue is not always obvious either in the clinic or in the research laboratory. The inherent subjectivity in detecting this excavation boundary can result in clinically significant differences in the quality and quantity of dentine removed by different operators and makes the in vitro comparison of newer excavation techniques more difficult. This article discusses the rationale behind carious dentine excavation and the criteria available to the dentist, both clinical and laboratory, to help identify the dentine requiring removal. PMID- 11218466 TI - Transcultural oral health care and the Chinese--an invisible community. AB - The Chinese, a 'silent minority', are the most scattered, but neglected, community in the UK. Most dentists will have at least a few Chinese people in their community. This paper describes the health beliefs, dental knowledge, attitudes and behaviours of the Chinese. Implications for general dental practitioners are discussed. PMID- 11218467 TI - Presentation of case reports. PMID- 11218465 TI - Oral cancer: 2. Clinical presentation and use of new knowledge about the biology of cancer to establish why tumours may recur. AB - This article describes the clinical presentations of oral cancer, and the development of a new generation of ultra-sensitive diagnostics to identify occult tumour and precancer, despite seemingly adequate treatment. PMID- 11218468 TI - Thrombophilia and dental surgery: a report of dental extraction in a patient with protein S deficiency. AB - Most patients with thrombophilia are asymptomatic. A case is presented here of a young woman with protein S deficiency, one of the thrombophilias, who required dental extraction. Protein S deficiency predisposes a very small number of those affected to life-threatening thromboses and emboli, for which they are required to take lifelong prophylactic anticoagulation. This report emphasizes the need to liaise closely with haematology departments when deciding whether heparinization is required for patients already taking warfarin. The role of low-molecular weight heparins is highlighted, a brief review of thrombophilia is given and the management of patients who are taking warfarin and need dental surgery is discussed. PMID- 11218469 TI - Name changes of drugs. PMID- 11218470 TI - A forgotten entity: 'broken needle while administering inferior dental block'. PMID- 11218471 TI - The atraumatic restorative treatment (ART) technique: does it have a place in everyday practice? PMID- 11218472 TI - C4 dispatches. PMID- 11218473 TI - Medical emergencies in the dental office. PMID- 11218474 TI - Dry mouth symptoms of Sjogren's syndrome. PMID- 11218475 TI - Latex allergy: ignorance and avoidance are not bliss. PMID- 11218476 TI - ADAA's answers to the most frequently asked questions about dental assisting professionalism. Interview by Jennifer Blake. PMID- 11218477 TI - A pat on the back? PMID- 11218478 TI - The occlusal management of maxillary anterior single-unit implant-supported restorations. AB - This paper, with the aid of clinical examples, highlights some of the common occlusal problems that can be associated with maxillary anterior single-unit implant-supported restorations. The authors stress the importance of thorough pre operative planning to identify any likely occlusal problems. This allows patients to be fully informed of the impact of any necessary clinical compromise and of the need for and nature of modifications to the natural dentition. PMID- 11218479 TI - Take two dentists: a tale of root caries. AB - Take two dentists, whose practices are about as different as they could possibly be, who both have a healthy respect for root caries. Our paper will start by describing these two practices and then review the literature to show what is known about the management of root caries. The paper ends by returning to the two dentists, who describe how the research reviewed in the literature may affect their work. PMID- 11218480 TI - An oral 'follicular' choristoma presenting in the anterior floor of the mouth. AB - A 46-year-old Asian man presented with hair growing from the anterior floor of his mouth. The diagnosis of this lesion was an oral choristoma of a 'follicular' variety. A choristoma is defined as an overgrowth of normal tissue at an abnormal site. Only one other case of this particular lesion has been reported to date. This article proposes mechanisms as to the aetiology of this lesion, and its inclusion in the classification of oral choristomas. PMID- 11218481 TI - Forget the sailboard--let's go whiteboarding! AB - This paper describes the electronic whiteboard, and discusses its potential as a clinical communication tool and its possible use in dental education. PMID- 11218482 TI - Oral cancer: 1. The genetic basis of the disease. AB - This article is in two parts. The first describes recent advances in our understanding of the biology of oral cancer and the potential to utilize this new information to make better predictions about outcome and devise new treatments. The second part describes the clinical presentation and the development of a new generation of ultra-sensitive diagnostics to identify occult tumour and precancer, to investigate why cancer may recur. PMID- 11218483 TI - The orthodontic restorative management of the peg-lateral. AB - There are usually two orthodontic options in dealing with the peg-lateral. First, the lateral incisor can be extracted and the resultant space closed. However, this will often give a narrow unaesthetic smile. The canine is too yellow and the gingival margin is too high. The second, preferred, option is often to open the space mesial and distal to the peg-lateral and create a proper space for a normal sized lateral incisor. The restorative dentist has to build up the peg-lateral to simulate a normal-sized lateral incisor. PMID- 11218484 TI - Walmsley's Web watch. AB - The ADEE site serves as a portal to other educational sites around the world. The address can be book-marked and used as a focus to explore and use the Web in a constructive way without becoming overwhelmed with the large amount of information that is present. There are, of course, many other sites that act as a resource and contain links to other web pages. This site is simple to use, contains links to web pages that are of high quality and will prove useful to people wishing to update their current knowledge. PMID- 11218485 TI - A fresh look at effective telephone screening. Part 2: Handling specific types of calls. PMID- 11218486 TI - Surface barriers. PMID- 11218487 TI - How dental assistants can avoid common problems found in panoramic images. PMID- 11218488 TI - A 2-year clinical study of composite and ceramic inlays. AB - Objective long-term clinical data are necessary to evaluate the performance of dental restorations. This prospective clinical trial evaluated composite and ceramic inlays for clinical acceptability as restorative materials in posterior teeth and provided 2-year results. The study involved 7 student operators placing 47 composite inlays (Tetric, blend-a-lux, Pertac) and 24 ceramic inlays (Empress) under the supervision of an experienced dentist. Clinical assessment of 56 inlays (78.9%) was performed after 2 years with modified USPHS criteria and statistically analyzed using the Mann-Whitney U test and Fisher's exact test. All the ceramic inlays and 90% of the composite inlays were considered clinically excellent or acceptable. During the first year 3 composite inlays failed and during the second evaluation period 1 had to be replaced. Ceramic inlays produced significantly better "anatomic form of the surface" (P = 0.038) and "integrity of the restoration" values (P = 0.043). Inlays in small cavities exhibited superior "marginal integrity" (P = 0.026) and "marginal discoloration" values (P = 0.034). Fisher's test revealed a significantly higher failure rate in molars than in bicuspids (P = 0.034). Posterior tooth-colored inlays exhibited a success rate of 100% for ceramic inlays and 90% for composite inlays even if placed by relatively inexperienced but supervised student operators. PMID- 11218489 TI - Retrospective clinical study and survival analysis on partial ceramic crowns: results up to 7 years. AB - The purpose of the present study was to determine retrospectively the clinical performance of 42 all-ceramic partial crowns (PCCs) placed during the past 7 years. All patients (n = 25) with partial ceramic crowns (n = 49) placed by one experienced dentist between 1992 and 1999 were asked to take part in a clinical study, and 22 patients with 42 restorations agreed to do so. All partial ceramic crowns studied were fabricated using the IPS-Empress I all-ceramic system (Vivadent). The following luting composites were used for placing the restorations: 20 (47.6%) Variolink high viscosity (Vivadent), 3 (7.1%) Variolink ultra (Vivadent), 17 (40.5%) Dual Zement (Vivadent), and 2 (4.8%) Compolute (Espe). The partial ceramic crowns were examined clinically using the modified USPHS criteria. Of the 42 restorations, 40 (95.2%) were still in function without any need of replacement. One restoration (2.4%) had failed before starting the clinical study, and another one (2.4%) fractured during the study. Twenty-eight (66.7%) of the partial ceramic crowns evaluated were rated Alpha with respect to marginal adaptation. Twelve (28.6%) restorations were rated Bravo, no Charlie ratings were found and 2 (4.7%) restorations were rated Delta. The Kaplan-Meier analysis was used to calculate the survival rate. The probability of survival (95% confidence interval) for 7 years was 81% (66-96%). These data indicate that partial ceramic crowns may provide successful esthetic restorations in posterior teeth. PMID- 11218490 TI - Relation between mercury concentrations in saliva, blood, and urine in subjects with amalgam restorations. AB - The aim was to determine the relationship between mercury content of resting and stimulated saliva, and blood and urine. Eighty subjects participated; 40 of them attributed their self-reported complaints to dental amalgam (patients), the others were matched with respect to age, sex and amalgam restorations (controls). Serum, 24-h urine, resting and chewing stimulated saliva were analyzed for mercury using the ASS-technique. Quality, number, surfaces and total area of amalgam fillings were recorded clinically and using study models. Median (range) mercury levels in serum were 0.67 (0.1-1.52) microgram/l for patients and 0.60 (0.1-1.3) for controls. In urine levels were found to be 0.77 (0.11-5.16) and 0.94 (0.17-3.01) microgram/g creatinine respectively. No significant differences were found between the groups. Resting saliva contained 2.97 (0.10-45.46) micrograms/l in patients and 3.69 (0.34-55.41) in controls (not significant). Chewing mobilized an additional amount of 16.78 (-6.97 to 149.78) micrograms/l in patients and 49.49 (-1.36 to 504.63) in controls (P < or = 0.01). Only a weak correlation was found between mobilized mercury in saliva and serum (r = 0.27; P < or = 0.05) or urine (r = 0.47; P < or = 0.001). For resting saliva the respective values were r = 0.45 (P < or = 0.001) and r = 0.60 (P < or = 0.001). Saliva testing is not an appropriate measure for estimating the mercury burden derived from dental amalgam. PMID- 11218491 TI - Site-specific association between supragingival plaque and bleeding upon probing in young adults. AB - The aim of the present study was to consider supragingival plaque as a risk factor for gingivitis in a group of young adults without destructive periodontal disease. A total of 127 subjects, 17 to 30 years of age, participated. Periodontal probing depth, clinical attachment level as well as bleeding upon probing and supragingival plaque was assessed at 6 sites of every tooth present. The individual odds ratios between plaque and bleeding ranged between 0.237 and 66.6. 23% volunteers had an odds ratio of below 1.2. Only 15% individuals presented with an attributable risk of supragingival plaque for bleeding upon probing of 50% or more. Overall, the odds of bleeding, adjusted for periodontal probing depth, was increased by 67% in the presence of plaque. Large differences were observed at different teeth with the highest odds ratio at mandibular premolars with 2.557 (95% confidence interval 2.033-3.216) and the lowest at maxillary molars with 1.355 (1.161-1.732). It was concluded that there was high interindividual and intraindividual variation of the relative risk for bleeding in the presence of plaque. The observed low overall relative risk has important consequences in educational and health care programmes since the risk of supragingival plaque which is actually attributable for the observed bleeding on probing may be rather small. PMID- 11218492 TI - Compatibility of resorbable and nonresorbable guided tissue regeneration membranes in cultures of primary human periodontal ligament fibroblasts and human osteoblast-like cells. AB - The purpose of this study was (a) to evaluate the cytocompatibility of three resorbable and nonresorbable membranes in fibroblast and osteoblast-like cell cultures and (b) to observe the growth of those cells on the various barriers by scanning electron microscopy (SEM). Primary human periodontal ligament fibroblasts (HPLF) and human osteoblast-like cells (SAOS-2) were incubated with nonresorbable polytetrafluoroethylene (ePTFE) barriers and resorbable polylactic acid as well as collagen membranes. Cytotoxic effects were determined by XTT (mitochondrial metabolic activity) and sulforhodamine B assays (cellular protein content). In addition, HPLF and SAOS-2 grown for 21 days on the investigated barriers were evaluated by SEM. Data were analyzed statistically by ANOVA using the Wilcoxon-Mann-Whitney test (P < 0.05). No changes were established in the periodontal ligament fibroblasts and human osteoblast-like cells after incubation with the collagen membrane. Cytotoxic effects, however, were induced by the polylactic acid barrier which slightly inhibited cell metabolism of the periodontal fibroblasts (XTT: 90.1% +/- 3.6 of control value). Moderate cytotoxic reactions were caused by the nonresorbable ePTFE membrane in HPLF-cultures (XTT: 82.7% +/- 3.5) and osteoblast-like cell monolayers (XTT: 80.0% +/- 0.6%). Mitochondrial activity in both cell cultures was significantly reduced by ePTFE barriers in comparison to non-incubated control cells (P = 0.028). SEM analysis of cell behavior on barriers demonstrated the differences between these materials: collagen barriers were densely populated with HPLF and SAOS-2, whereas only few or no cells were seen to adhere to the ePTFE and polylactic acid membranes. Our findings indicate that the collagen barrier investigated is very cytocompatible and may be integrated into connective tissue well. On the contrary, the ePTFE and polylactic acid membranes induced slight to moderate cytotoxic reactions which may reduce cellular adhesion. Thus, gap formation between the barrier surface and the connective tissue may be promoted which may facilitate epithelial downgrowth and microbial accumulation. Consequently, these effects may reduce the potential gain in periodontal attachment. PMID- 11218494 TI - An in vitro study of fluoride release from a resin-modified glass ionomer cement after exposure to toothpaste slurries of different pH. AB - The aim of the study was to evaluate the fluoride release from an aged resin modified glass ionomer (Vitremer) after exposure to five toothpaste slurries with different pH values. Cylindrical specimens of the material were leached in de ionized water for 3 months and then exposed for 30 min daily for 10 days to three dentifrice slurries (20 specimens/group) containing 0.05% fluoride with pH values of 2.6, 5.7 and 8.3 and two non-fluoridated slurries with pH values of 2.5 and 5.7. A neutral NaF solution (0.05% F) was used as a control. During the 30 min exposure time, the fluoride concentration was gradually decreased in order to imitate the clinical situation. Thereafter, specimens were immersed individually in de-ionized water and the fluoride release determined. After the first day of exposure, all groups except one without fluoride (pH 5.7) showed significantly (P < 0.05) increased fluoride release. After exposure to the fluoridated toothpaste slurry with pH 5.7, significantly (P < 0.05) more fluoride was released compared to the toothpaste slurry with pH 8.3. Low pH (2.5 or 2.6) of the slurry resulted in a significantly (P < 0.05) higher fluoride release, regardless of whether it was fluoridated or not. The total amount of fluoride released after exposure to the more acidic fluoride toothpaste slurry was greater than that released from the more acidic non-fluoride toothpaste and the less acidic fluoride toothpaste. Our data indicate that the fluoride release from the resin-modified glass ionomer studied may be increased after treatment with an acidified NaF-toothpaste. PMID- 11218493 TI - Oral Chlamydia trachomatis in patients with established periodontitis. AB - Periodontitis is considered a consequence of a pathogenic microbial infection at the periodontal site and host susceptibility factors. Periodontal research supports the association of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, and Bacteroides forsythus, and periodontitis; however, causality has not been demonstrated. In pursuit of the etiology of periodontitis, we hypothesized that the intracellular bacteria Chlamydia trachomatis may play a role. As a first step, a cross-sectional study of dental school clinic patients with established periodontitis were assessed for the presence of C. trachomatis in the oral cavity, and in particular from the lining epithelium of periodontal sites. C. trachomatis was detected using a direct fluorescent monoclonal antibody (DFA) in oral specimens from 7% (6/87) of the patients. Four patients tested positive in specimens from the lining epithelium of diseased periodontal sites, one patient tested positive in healthy periodontal sites, and one patient tested positive in the general mucosal specimen. In conclusion, this study provides preliminary evidence of C. trachomatis in the periodontal sites. Planned studies include the use of a more precise periodontal epithelial cell collection device, the newer nucleic acid amplification techniques to detect C. trachomatis, and additional populations to determine the association of C. trachomatis and periodontitis. PMID- 11218495 TI - An attempt to explain why Tanzanian children drinking water containing 0.2 or 3.6 mg fluoride per liter exhibit a similar level of dental fluorosis. AB - The aim of this study was to identify factors that might explain the similar level of prevalence and severity of dental fluorosis in two neighboring areas in Tanzania: Kibosho; 0.2 mg fluoride/l, n = 96 and Arusha; 3.6 mg fluoride/l in drinking water, n = 80. Subjects aged 8-16 years were examined for dental fluorosis using the Thylstrup and Fejerskov Index (TFI). Based on the score on the upper left central incisor, the prevalence was not significantly different between the communities (TFI > or = 1). The severity, however, was significantly higher in Arusha. The areas had different food habits, e.g., type of weaning food used, and the use of magadi, a fluoride containing salt. In Arusha, 99% of the children had been given lishe, which is a magadi-free weaning food. Conversely in Kibosho, 61% used lishe while 39% used the magadi-containing weaning food kiborou. Magadi was used as food tenderizer in 'adult food' by 98% in Kibosho and 45% in Arusha. Residential area and use of magadi explained 5% of the variance in TFI scores in inter-area analyses. In intra-area analyses, weaning food in Kibosho and use of magadi in Arusha had a significant effect, but the total explained variance was only 5 and 4%, respectively. Apart from fluoride in the drinking water, other sources of fluoride such as use of magadi in weaning food (kiborou) and in the adult food may partly explain the high prevalence and severity of dental fluorosis in the community with 0.2 mg fluoride per liter in the drinking water. PMID- 11218496 TI - The bicarbonate concentration in human saliva does not exceed the plasma level under normal physiological conditions. AB - Depending on the secretion rate and nature of the stimulus applied, the bicarbonate concentration ([HCO3-]) in human saliva has been shown to vary from 1 to 60 mM, with the highest values obtained in secretions from the parotid and submandibular glands. We conducted the present study on five healthy young males, in order to determine whether human saliva [HCO3-] can exceed the plasma level under normal physiological conditions, and applied a strategy in which we measured the secretory response to various stimulus intensities. Whole saliva stimulation was initiated by chewing paraffin (50-100 chewing cycles/min), parotid saliva stimulation by citric acid taste (0.2-4% citric acid solutions), and both secretions were also collected during systemic medication using pilocarpine (5 mg). Our results showed that the parotid and whole saliva flow rates were closely correlated to the intensity of the secretion-inducing stimulus applied (taste, chewing, and pilocarpine). This was also the case for saliva [HCO3-], all of which was present in the form of physically dissolved CO2, H2CO3, and HCO3-. The highest mean [HCO3-] (i.e. 37.75 mM) was found in parotid saliva after stimulation by pilocarpine in combination with 4% citric acid taste. Under normal physiological conditions (i.e. without pilocarpine) the saliva [HCO3-] was similar to or below the plasma level in both secretions. PMID- 11218498 TI - Bone sialoprotein-induced reparative dentinogenesis in the pulp of rat's molar. AB - Bone sialoprotein (BSP), an osteogenic protein (OP), mixed with a carrier, was implanted in the pulp of rat first upper molars (OP group). Cavities were prepared with dental burs and pulp perforation was carried out by pressure with the tip of a steel probe. After 8, 14, and 30 days, the rats were killed and the pulps of the OP group were compared with (1) a sham group (S group), (2) a group where the carrier was implanted alone (C group), and (3) capping with calcium hydroxide (Ca group). After 8 days, a few inflammatory cells were seen, mostly located at the pulp surface near the perforation. In the Ca group, a dentin bridge started to form, in contrast to the other groups. After 15 days, globular structures were seen in the pulps of the S and C groups. A reparative osteodentin bridge isolated the pulp from the cavity in the Ca group. Variable reactions were seen in the OP group, with some evidence of cell and matrix alignments or plugs of osteodentin in continuity with an inner layer of reparative dentin. After 30 days, irregular osteodentin formation was observed in the pulps of the S and C groups, with a tendency for globular structures to merge, but with interglobular spaces filled by pulp remnants. In the Ca group, osteodentin was observed in the mesial part of the pulp chamber. In the BSP-implanted group, the osteogenic protein stimulated the formation of a homogeneous dentin-like deposit occupying most of the mesial part of the pulp. Apparently, BSP stimulates the differentiation of cells which secrete an organized extracellular matrix more efficiently than any other capping material used so far. Altogether, the results reported here support that bone sialoprotein displays novel bioactive properties and is capable of stimulating in 1 month's time the development of a thick reparative dentinal tissue in the pulp, occluding the perforation and filling the mesial third of the pulp chamber. PMID- 11218499 TI - Emdogain--periodontal regeneration based on biomimicry. AB - Biomimicry has been introduced as a term for innovations inspired by nature [1]. Such innovations may appear in almost every part of modern society. This review on the effects of enamel matrix proteins on the formation of cementum and the development of emdogain for regeneration of periodontal tissues lost due to periodontitis shows an example of biomimicry in dentistry. Findings from clinical and laboratory investigations are summarized and the biological basis for enamel matrix-induced periodontal regeneration is discussed. PMID- 11218497 TI - Terminal end of the human odontoblast processes. PMID- 11218500 TI - Tools for tissue engineering of mineralized oral structures. AB - This paper presents a short review of three groups of tools which can be or are used for the tissue engineering of mineralized oral structures: growth factor delivery systems (GFDS) and surface bioactivation with covalent bound peptides or with nanomechanically linked proteins. According to the reported personal experience of the authors, GFDS have to face the following challenging issue before being used routinely in dentistry, e.g., as a tool for reparative dentinogenesis or bone healing: adaptation of the GFDS design to the tissue where it will be implanted in order to deliver the right dose of growth factor (GF) at the right time. The bioactivation of surfaces, for example of dental implants, with covalent bound peptides or nanomechanically linked proteins represents a second innovative way to improve dental health in the future. Here we report on the experimental use of cyclic RGD peptides grafted on polymethylmethacrylate to improve osteoblast adhesion. Furthermore, we show the potential advantage of immobilizing and incorporating collagen I on titanium implant surfaces. These techniques or a combination of them will help to create improvements, for example, of dental implants in the near future. They will also help to promote bone and dentin regeneration. PMID- 11218501 TI - Basic research meets dentistry. PMID- 11218502 TI - Ehlers-Danlos type VIII. Review of the literature. AB - Ehlers-Danlos type VIII is a rare disorder characterized by soft, hyperextensible skin, abnormal scarring, easy bruising, and generalized periodontitis with early loss of teeth. To illustrate the clinical dermatological and dental features, we present the case history of a 20-year-old patient who has suffered from poor healing of wounds at the shins and knees since childhood, which have developed into hyperpigmented atrophic scars. In the course of orthodontic treatment during the last 3 years, severe apical root resorption, gingival recession, and loss of alveolar bone were observed. Family history was noncontributory for any skin or tooth disorders. The typical clinical signs confirmed the diagnosis of Ehlers Danlos syndrome type VIII. As there is no specific treatment for the disorder, management is limited to the symptomatic treatment of the dental disease. It seems advisable to consider carefully the indications for orthodontic treatment in patients with Ehlers-Danlos type VIII syndrome. PMID- 11218504 TI - Clinical evaluation of removable partial dentures 10 years after insertion: success rates, hygienic problems, and technical failures. AB - The aim of this retrospective study was to examine the condition and success rate of various designs of removable partial dentures 10 years after placement. Seventy-four patients treated with 101 mainly conical crown-retained dentures (CCRDs), clasp-retained removable partial dentures (RPDs), or a combination of conical crown and clasp-retained dentures (CRPDs) were reexamined. Prosthetic findings were compared to baseline values at insertion and checked for factors that may affect them. Overall, 36.6% of the prostheses were regarded as successes, 23.8% as partial successes, and 39.6% as failures. Also, only one third of the prostheses showed neither hygienic problems nor technical failures. The statistical analysis identified no single parameter as significantly affecting the success rate of the partial dentures. Prostheses supported by several abutment teeth had improved success, and RPDs had a higher failure rate (66.7%) than CCRDs (33.3%) and CRPDs (44.8%); however, because of the limited number of RPDs these differences were not statistically significant. Although the prostheses were unsupervised in service, the 60.4% overall success rate of the dentures was somewhat higher than in other studies on precision-retained prostheses. PMID- 11218503 TI - Clinical and antibacterial effect of tea tree oil--a pilot study. AB - The aim of this clinical pilot study was to compare the effect of tea tree oil with the effect of water and chlorhexidine on supragingival plaque formation and vitality. Eight subjects were asked to refrain from any kind of mechanical oral hygiene for 4 days after professional tooth cleaning (day 0), and to rinse with water instead for 1 week, with chlorhexidine in a second and tea tree oil in a third test week. The plaque index (PI), which was evaluated daily (days 1-4), served as a clinical control parameter. On the last day of the study (day 4), the plaque covering the front teeth was stained, photographed, and therefrom the plaque area (PA; %) was estimated using a digital measuring system. Each day of the study (days 1-4), the sampled plaque was examined using a vital fluorescence technique. Tea tree oil reduced neither the clinical parameters (PI and PA) nor the vitality of the plaque flora significantly. Within the limitations of the study design, it was determined that a solution with tea tree oil--utilized as ordinary mouthwash--has no positive effect on the quantity or quality of supragingival plaque. PMID- 11218505 TI - Effect of transcutaneous electrical nerve stimulation on pain perception threshold of human teeth: a double-blind, placebo-controlled study. AB - In this double-blind, placebo-controlled study, we studied the effect of three different transcutaneous electrical nerve stimulation (TENS) devices with extra- and intraoral electrodes on the pain perception thresholds of 234 unrestored, caries-free human teeth of 66 healthy individuals subjected to stimulation with an electric pulp tester. A placebo control collective of 64 healthy subjects received no electrical stimulation, since an inactive TENS device was used. In all tooth types tested (maxillary and mandibular incisors and premolars), the use of the active TENS devices resulted in an increase of 16.3-32.5% versus baseline in the pain perception threshold. The differences between active TENS and baseline were statistically significant for both TENS devices using extraoral electrodes (P < 0.05). No statistically significant differences were found between the different devices tested (P > 0.05). In the placebo collective, the increase in the pain perception threshold ranged between 6.4% and 10.3% versus baseline. There were no significant differences between placebo TENS and baseline on the one hand and between placebo TENS and the active TENS devices on the other hand (P > 0.05). The findings suggest that, as an alternative to local anesthetics, TENS seems not to be useful in the case of painful dental interventions, since it offered only minor advantages over a placebo. PMID- 11218506 TI - Technical failure rates of double crown-retained removable partial dentures. AB - Removable partial dentures (RPD) can be retained using conical crowns or parallel sided telescopic double crowns. The purpose of this study was to evaluate and compare the technical failure rate of the two retainer systems. One hundred seventeen dentures made by dentists of the medical school were included. Seventy four RPD were retained with parallel-sided crowns (n = 251) and 43 with conical crowns (n = 160). Following the medical report follow-ups from January 1992 to December 1998, technical RPD failures were noted and analyzed. Technical problems occurred during the observation time in 48.8% of the conical retained dentures and 34.2% of the parallel-sided retained dentures. In both cases, loss of cementation was most frequently noted, while loss of the facings occurred only with conical crowns. Other technical failures did not depend on the type of retainer system used. These were most frequently problems with the denture base, e.g., fracture of artificial teeth or the metal framework. We conclude that there were different technical failures of both double crown retainer systems. These problems were not insignificant in number but treatable. PMID- 11218507 TI - Power toothbrushes, gender, and dentin hypersensitivity. AB - Power toothbrushes require less force for plaque removal than manual brushes. In addition, in vitro studies have indicated that brushing with low force could occlude patent dentin tubules by formation of a smear layer. Hence, lessening the force necessary to remove plaque may reduce dentin hypersensitivity. However, it was recently suggested that the use of an oscillating/rotating power toothbrush could decrease tooth sensitivity as compared to a sonic power toothbrush. Therefore, the objective of the present research was to compare the effect on dentin hypersensitivity of two different types of power brushes, the Optiva Sonicare and the Braun Oral B Ultra Plaque Remover. The null hypothesis was tested in an 8-week, randomized, parallel group, examiner-blind clinical trial. Fifty-nine subjects with a history of dentin hypersensitivity participated. Dentin hypersensitivity-associated pain was elicited using tactile and evaporative stimuli and assessed using a visual analog scale (VAS) instrument. Clinical examinations were carried out at screening and baseline and repeated after 8 weeks of twice daily use of the power brushes. Data analysis was performed on VAS scores obtained at the final visit following adjustment for group differences at baseline. A 35% to 40% reduction in pain as compared to baseline was observed in both treatment groups. Treatment-related differences were not statistically significant. A gender-related effect on dentin hypersensitivity was observed using the tactile stimulus and may merit further investigation. PMID- 11218508 TI - The effect of splinting of teeth in combination with reconstructive periodontal surgery in humans. AB - The purpose of this study was to evaluate the effect of splinting teeth on the results of periodontal reconstructive surgery using a specific carbonate bone replacement graft (BRG) material. Forty-five patients were randomly treated with a periodontal surgery approach. Natural coral calcium BRG was utilised in 33 patients. This 33-patient group was divided into three equal groups. In the presplint group, teeth were splinted to at least two rigid teeth before surgery, in the postsplint group, teeth were splinted at suture removal, and in the nonsplint group, the treated teeth were not splinted at all. In 12 patients, teeth were treated with surgical debridement (DEBR) alone and not splinted. Periodontal probing depth (PPD), clinical probing attachment level (CPAL), and tooth mobility were measured using desmodontometry (DDM) and periotest (PTV) with reproducible methods before surgery and at various periods up to 1 year afterwards. A decrease in PPD (5.4 mm, SD 1.4 mm) and tooth mobility (DDM horizontal 257 microns, SD 60 microns) and a gain of CPAL (5.1 mm, SD 1.4 mm) were seen following the use of BRG in presplint teeth. In the same group, PPD and tooth mobility were significantly reduced compared to nonsplint teeth. DEBR alone showed reductions in tooth mobility and PPD and a significantly smaller gain in CPAL than in presplint teeth treated with BRG. The less favourable improvement in periodontal function of postsplint or nonsplint teeth seemed to be due to the loss of BRG material caused by tooth mobility. These results indicate that an undisturbed wound healing process using BRG together with tooth stability is beneficial to overall clinical success. PMID- 11218509 TI - Inserts--megafillers in composite restorations: a literature review. AB - Modern insert systems have been available on the dental market since the late 1980s. In general, two major systems can be distinguished: those with and those without preparation instruments in combination with matching standardized inserts. It is claimed that one of the advantages of insert systems is the better marginal adaptation of insert/composite restorations compared to mere composite restorations: the integration of inserts reduces the polymerization shrinkage stress and lowers the overall coefficient of thermal expansion. In vitro data indicate that adapting the insert size to the most precise fit produces a quality of marginal adaptation comparable to that of ceramic inlays. Inserts also facilitate the establishment of a proximal contact. With respect to wear, no significant differences are detected between composite and insert restorations. The bond between insert and composite is susceptible to contamination during operative procedures. Short-term clinical investigations confirm in vitro findings regarding improved marginal adaptation and increased wear resistance. Long-term controlled clinical studies are in progress, but data are not yet available. Based upon the present in vitro and in vivo data it can be concluded that the insert technology shows promising results, but further investigations regarding, for example, stability of the insert/composite bond, fracture resistance of the overall restoration, and wear behavior are necessary to predict the clinical success of this alternative restoration procedure. PMID- 11218510 TI - Time dependent failure rate and marginal bone loss of implant supported prostheses: a 15-year follow-up study. AB - This study deals with 4971 implants (Branemark system) installed in 1315 patients, either fully or partially edentulous, and followed from implant installation up to the last control. A predominance of female patients (61%) and a nearly equal number of upper and lower jaws characterised the study group. Patients were scheduled each 6-12 months for recall. The observation time varied from 0.5 to 15 years (mean 5.1). The whole cohort was split up into compromised (n = 59) and non-compromised (n = 1256) patients. The former are defined as grafted (autologous bone) and patients irradiated in the head and neck area. In the compromised patients 24 out of 59 patients (40.6%) showed failures, in whom 59 out of 310 (19%) implants failed. In the non-compromised patients, implant failures were observed in 11.6% of the patients, which corresponds to 5.9% of the installed implants, excluding iatrogenic failures. Failures were further divided chronologically into early (up to 1 year after abutment connection) and late failures. There were early implant failures in 12.5% of the compromised patients and in 3.4% of the others. Late implant failures occurred in 7.4 and 2% of the two patients groups, respectively. While gender did not affect the failure rate, implant lengths, corresponding to the available bone height did, since a 21.5% failure rate for the 7-mm implants contrasts with 4.1 and 3.8% for 13- and 15-mm implants, respectively. Early as well as annual late failures are more frequently found in the maxilla. Implant fractures only occurred in the fixed (both partial and full) prosthesis group but never surpassed the 0.2% annual level. Marginal bone loss, exceeding the third screw thread occurred in 1.8% of the implants at the last control. It appears that this type of implant configuration offers a high long-term predictability. Failures occur before, at or during the first year after abutment connection and in very short implants. Marginal bone as a whole is very stable over the years. PMID- 11218511 TI - Salivary arginase in patients with adult periodontitis. AB - Human saliva has been shown to possess enzymatic activities, one of which is derived from arginase. Arginase is known to be an arginine-depleting enzyme belonging to the L-arginine/nitric oxide pathway. The aim of this study was to examine the possible role of arginase activity of saliva in the pathogenesis of periodontal disease. Mixed saliva samples were collected from 20 adult periodontitis patients and 15 systemically and periodontally healthy subjects. Salivary arginase and total protein contents were determined by using spectrophotometrical enzyme analysis and salivary arginase was expressed as specific activity. Periodontal disease status was determined by clinical periodontal assessments including probing pocket depth, clinical attachment level, plaque index and gingival index. While the increase in total protein was not statistically significant, arginase levels in the patient group were significantly higher than the controls. All periodontal indices were found to be significantly higher in the periodontitis group, but no meaningful correlation was observed between the biochemical and periodontal variables in both groups. Furthermore, no significant correlation existed between the amount of arginase and total protein. In conclusion, it was suggested that salivary arginase activity in periodontitis along with the arginine-nitric oxide pathway may be involved in the disease process by using the common substrate L-arginine and inhibiting nitric oxide production. PMID- 11218512 TI - Comparison of failure rates of adhesive-fixed partial dentures for in vivo and in vitro studies. AB - The objective was to investigate associations between the results of an in vitro and an in vivo study using an artificial mouth and a study of adhesive fixed partial dentures (AFPD) begun in 1985 [1]. Twenty extracted human molars and 20 human upper incisors were inserted into PMMA resin, 6 mm apart to represent a gap. Two preparation methods (identical to those in in vivo conditions) were used: a retentive preparation technique (posterior) and a non-retentive preparation technique (anterior). The frameworks of the bridges consisted of CoCr alloy with a ceramic veneered pontic to replace the missing tooth. The bonding surfaces of the posterior AFPDs were conditioned with a tribochemical system, while the anterior AFPDs were sandblasted. All AFPDs were inserted using a dual curing composite cement. During thermal-cycling and mechanical loading (TCML: 6000 x 5 degrees C, 1.2 x 10(6) x 50 N, 1.66 Hz) in an artificial environment, the frequency and type of failures were observed. The above mentioned loading parameters were hypothesized to represent a period of 5 years under oral conditions. The results were compared to those of similar bridge-types in the in vivo study. The Kaplan-Meier estimations showed similar graphs for in vivo and in vitro with both types of AFPDs. In vivo and in vitro, the retentively prepared AFPDs were markedly more successful. With regard to the failure types, the simulation-parameters seemed to represent a loading stress that was comparable to in vivo conditions. PMID- 11218513 TI - Fluoride concentration in plaque in adolescents after topical application of different fluoride varnishes. AB - The aim of the study was to measure the fluoride (F) concentration in plaque after a single topical application of different fluoride varnishes with contrasting levels of F. Thirty adolescents (12-17 years) with fixed orthodontic appliances were randomly assigned to one of three groups: Bifluoride (6% F), Duraphat (2.23% F) and Fluor Protector (0.1% F). The varnishes were applied after professional cleaning in one upper quadrant, leaving the opposite quadrant untreated according to the split-mouth technique. Pooled plaque samples from each quadrant were collected at baseline and 3 days, 7 days and 30 days after the varnish treatment, and fluoride was analysed by microdiffusion. All fluoride varnishes increased the fluoride concentration in plaque compared with baseline, and the mean values varied between 23 and 138 ng F/mg after 3 days, depending on varnish F concentration. Compared with the control quadrant, statistically significant elevations were recorded for Bifluoride after 3 days and 7 days and Duraphat after 3 days, while no significant differences were revealed in the Fluor Protector group. The fluoride concentration in plaque was back to baseline levels for all participants in the Duraphat group after 7 days, while some individuals in the Bifluoride and Fluor Protector groups still registered slightly increased levels after 30 days. The results suggest that fluoride varnish treatments resulted in elevated fluoride levels in plaque adjacent to fixed orthodontic appliances for a period of up to 1 week, although different patterns was disclosed for the various brands. PMID- 11218514 TI - Infection of primary human gingival fibroblasts by Porphyromonas gingivalis and Prevotella intermedia. AB - Adhesion and penetration of clinical isolates of Porphyromonas gingivalis and Prevotella intermedia in human gingival fibroblast monolayers were studied by transmission electron microscopy (TEM). Fibroblasts were cultured from biopsies of human healthy gingiva. Porphyromonas gingivalis and Prevotella intermedia were isolated from patients with periodontitis. Fibroblasts were incubated with microorganisms in an antibiotic-free medium for 24 h. Then cultures were washed to remove nonadherent bacteria. Consecutively, infected cultures were grown for another 24 h. Thereafter, the treated monolayers were prepared for TEM investigations. Internalized Porphyromonas gingivalis and Prevotella intermedia were visible after 24 h of incubation. Prevotella intermedia showed only division in cytoplasm of fibroblasts after 24 h and 48 h incubations. Infected fibroblasts revealed various morphological alterations such as extensive vacuolization and breakdown of mitochondria. These findings demonstrate that Porphyromonas gingivalis and Prevotella intermedia may invade human gingival fibroblasts and thus may damage these cells directly or due to the release of microbial cytotoxic components. PMID- 11218515 TI - Influence of a high-speed polymerization method on the marginal integrity of composite fillings in Class-II cavities. AB - The aim of this study was to evaluate the effect of a rapid photopolymerization method on the marginal integrity of composite fillings. Ninety two-surface cavities were prepared in extracted human molars using the SonicSys preparation system. All cavities were bonded with one bonding agent (Syntac) and filled with a microfilled composite (Herculite XRV), a heavy filled composite (Z100 MP), and an Ormocer (Definite) in two increments. Each increment had a thickness of approximately 1.5 mm and was polymerized using either halogen light or the plasma light of Apollo 95 E. In this process, six trial groups each containing 15 fillings were created. After replicas were made, the test teeth were subjected to a thermocycling process of 2000 temperature cycles (5 degrees C/55 degrees C) followed by a wear simulation of 50,000 stress cycles each with 50 N. This was followed by the creation of a second set of replicas, quantitative margin analysis, and dye penetration. A significant (P < 0.05) influence of the thermomechanical stress and a significant (P < 0.05) influence of the factor "material" were shown for the margin criterion "continuous margin" using MANOVA. The factor "light source" produced no significant influence (P = 0.57) on the amount of continuous margin. During the dye penetration, no significant differences between the polymerization methods could be established with the materials Herculite XRV and Z100 MP (H-test according to Kruskall and Wallis). Only with the material Definite was a significantly higher dye penetration observed at the occlusal measuring point in the plasma light group. A rapid polymerization with high light intensity had no adverse effects on the margin quality within the limitations of this in vitro study. However the marginal integrity might have been influenced by the chosen adhesive system/composite resin combination, which does not represent the respective product line. Additionally, further studies ought to show which exposure time is necessary for a sufficient degree of conversion. PMID- 11218516 TI - Healing of fenestration-type defects following treatment with guided tissue regeneration or enamel matrix proteins. An experimental study in monkeys. AB - The aim of the present study was to evaluate histologically in monkeys the healing in acute fenestration-type defects following treatment with guided tissue regeneration (GTR) or enamel matrix proteins (EMD). Standardized "critical size" fenestration-type defects were produced surgically at the vestibular aspect of teeth 13, 23, 33, 43 in three monkeys (Macaca fascicularis). The vestibular bone plates were removed and the root surfaces were debrided by means of hand instruments in order to completely remove the root cementum. Following root conditioning with ethylenediaminetetraacetate (EDTA), the defects were treated using one of the following therapies: (1) GTR, (2) EMD, or (3) control (coronally repositioned flaps). After 5 months the animals were killed and perfused with 10% buffered formalin for fixation. Specimens containing the defects and surrounding tissues were dissected free, decalcified in EDTA, and embedded in paraffin. Eight micrometer-thick step serial histological sections were cut in a vestibulo-oral direction, stained with hematoxylin and eosin or oxone-aldehyde-fuchsin-Halmi, and subsequently examined under the light microscope. The results showed that, in the defects treated with GTR, a new connective tissue attachment (i.e., new cementum with inserting collagen fibers) and new bone formation had consistently occurred, whereas, in the defects treated with EMD or with coronally repositioned flaps, new attachment and new bone reformed to a varying extent. The quality of the cementum did not differ after EMD, GTR, or flap surgery. It was concluded that GTR treatment with bioresorbable membranes seems to predictably promote new attachment and new bone formation, whereas the application of EDTA or EMD may also enhance periodontal healing to a certain extent. Further studies with higher numbers of animals and defects are needed in order to definitely clarify the effect of root surface conditioning with EDTA and EMD on periodontal healing. PMID- 11218517 TI - Dental variables associated with differences in severity of fluorosis within the permanent dentition. AB - The aim of this study was to assess the influence of age at start, duration, and completion of enamel formation, as well as of tooth-eruption age and enamel thickness on the severity of dental fluorosis within the permanent dentition. The material comprised Ugandan children (n = 219), aged 10-14 years, with 28 teeth and at least 1 tooth with fluorosis. The children were permanent residents in districts with either 0.5 mg or 2.5 mg fluoride/l in the drinking water. Fluorosis was assessed on the vestibular surfaces of all teeth using the modified Thylstrup and Fejerskov (TF) index. In order to relate fluorosis to the dental variables, the material was divided into a test group (n = 103), with fluorosis on all teeth, and a reference group (n = 116), with fluorosis on up to 27 teeth. The reference group was used to confirm or refute the findings in the test group. Paired comparisons showed significantly higher median TF scores for the late than for the early mineralizing and erupting teeth. In multiple regression analyses, the age at start, duration, and completion of enamel formation as well as tooth eruption was significantly related to the severity of fluorosis after controlling for enamel thickness (P < 0.05, n = 14). The effect (R2change) of the dental variables on the variation in severity of fluorosis within the dentition was in decreasing order: the duration of enamel formation, age at completion of enamel formation, tooth-eruption age, and the start of enamel formation. PMID- 11218518 TI - Acid formation in sucrose-exposed dental plaque in relation to caries incidence in schoolchildren. AB - The aim was to investigate the composition and concentration of organic acids produced by plaque bacteria in vivo and its possible relation to caries development in schoolchildren. Sucrose-exposed pooled plaque from 25 healthy teenagers was collected and the levels of Streptococcus mutans and lactobacilli were estimated. The acid anions were analysed with isotachophoresis. The prevalence and incidence of dental caries during a 2-year period was recorded. Depending on the amount of plaque collected, the subjects were divided into a low (n = 12) and a high (n = 13) plaque weight group. The dominating anions in sucrose exposed plaque were lactate, acetate and propionate. For the entire study group, no association was found between the total acid concentration and caries development but for the participants with low plaque weight a positive relationship (P < 0.01) was disclosed. No correlation was found between the concentrations of acids and the number of lactobacilli or Streptococcus mutans. The present results did not suggest that the acidogenicity of sugar-exposed pooled plaque samples was a suitable indicator of caries activity in teenagers. PMID- 11218519 TI - From black to white? PMID- 11218520 TI - The management of occupational exposures to blood and saliva in dental practice. AB - Accidental injuries when handling sharp or rotating instruments can allow inoculation of a dental team member by the patient's blood or saliva. The risk of transmission of HIV from occupational exposure among dental workers is low and to date no occupational exposure has resulted in HIV transmission. However, hepatitis B and C have a high morbidity and mortality and are more infectious than HIV. This paper demonstrates how occupational exposures to blood and saliva could be managed in general dental practice and outlines the legal responsibilities of a dentist in the management of these exposures. PMID- 11218522 TI - Current practice in endodontics. AB - The aim of this series of six articles is to improve the quality of endodontic treatment in general dental practice by considering what is currently being taught in dental schools. This first article considers the rationale behind endodontic treatment, what we are aiming to achieve and why. It looks at the dental and medico-legal issues which dictate the standards of our practice, and sets out the programme for the series. PMID- 11218521 TI - Contemporary resin-based composite materials for direct placement restorations: packables, flowables and others. AB - Resin-based composite (RBC) materials are composed of principal and diluent monomers, fillers, coupling agents and other components. These materials have been developed in recent years to produce packable and flowable materials, and materials which may release ions under specific conditions and which may contain fibres. Materials which are organic-inorganic copolymers have also become available. Long term clinical trial data are not available for the most recently introduced materials. PMID- 11218523 TI - Diagnosis of acromegaly in orofacial pain: two case reports. AB - Acromegaly is an uncommon condition, with an annual incidence in the UK of three per million. The gradual onset of the clinical features mean that often friends and relatives are unaware of the underlying pathology. In view of the morbidity, and indeed mortality, arising from undiagnosed cases, general dental practitioners and other healthcare workers should routinely take note of systemic as well as intra-oral changes occurring in their patients when seen on review. The association of paraesthesia, anaesthesia and pain with acromegaly is well documented. However, there appear to be few reports linking acromegaly with orofacial pain or dysaesthesia. This paper describes two such cases. PMID- 11218524 TI - Transcultural oral health care: 2. Developing transcultural oral health promotional materials. AB - This paper discusses the common problems involved in developing transcultural oral health promotional materials, and describes the best ways to avoid them. Translation errors and poor illustrations are by far the most frequently encountered problems followed by cultural incompatibility, inadequate information, and text and layout mistakes. PMID- 11218525 TI - Selection of materials for post cementation. AB - Many types of cement are available for post cementation, each with advantages and disadvantages. For posts with adequate mechanical retention, zinc phosphate is a good choice for patients for whom fluoride release is not considered essential. Posts with compromised mechanical retention benefit from use of a resin-modified glass-ionomer cement, which also releases fluoride. Composite resin cements should be reserved for rare cases where mechanical retention is so compromised that use of a resin-modified glass-ionomer cement provides inadequate retention. Great care is required when using composite resin cements to ensure optimum performance and avoid the creation of difficult-to-remove excess cement. Clinicians should be aware that posts cemented with resin-modified glass ionomer or composite resin cements may be difficult or impossible to remove if access to the root canal system is subsequently required. PMID- 11218526 TI - Periodontal signs and symptoms associated with vertical root fracture. AB - This report describes the clinical presentation of three cases of vertical root fractures in adult patients where an initial diagnosis of localized periodontitis had been considered. Loss of the affected tooth occurred in all of these patients. The effects of endodontic therapy and the provision of post-retained restorations are considered in relation to their potential effect of weakening the root and predisposing the tooth to vertical fracture. The last case presents an unrestored molar tooth with a complete vertical root fracture. PMID- 11218527 TI - More dental health. PMID- 11218528 TI - Modern thoughts on fissure sealants. AB - It has long been known that fissure sealants are an important part of the prevention and control of dental caries in pits and fissures. However, their usage is still sporadic and generally not related to evidence-based guidelines. Caries prevalence has changed since sealants were introduced and this has significant implications for the criteria on which to select patients who would most benefit from their usage. The clinical technique for successful fissure sealant application is very moisture and operator sensitive. However, there is accumulating evidence that use of fissure sealants can be extended, given suitable investigation, to the early carious lesion as a 'preventive resin restoration'. PMID- 11218529 TI - An alternative putty/wash impression technique. AB - Conventionally, custom trays have been made in the laboratory on casts constructed from preliminary impressions. A spaced tray made in this way allows a uniform thickness of impression material of approximately 2 mm which is said to enhance the accuracy of the impression-taking procedure. A technique is described to fulfill this criterion without the need for a primary impression, by constructing a spaced putty custom tray inside the mouth. PMID- 11218530 TI - Hormonal factors in periodontal disease. AB - This article discusses the effects of sex steroid hormones, glucocorticoids and insulin deficiency on periodontal tissues, and the possible consequences on periodontal disease progression. The androgens and oestrogens have predominantly anabolic functions in stimulating matrix synthesis, which is applicable to periodontal repair and medication-induced gingival overgrowth. Oestrogen and progesterone can contribute to pregnancy gingivitis; long-term use of hormonal contraceptives can accelerate progression of periodontal disease. Higher levels of circulating cortisol, associated with stress, can influence the onset of acute necrotic ulcerative gingivitis. Gingivitis and periodontal disease are reported to be more prevalent in type 1 and type 2 diabetes mellitus (periodontal disease, particularly in older, less well controlled subjects) than in non-diabetic individuals. PMID- 11218531 TI - It ain't what you say.... legibility and clarity of treatment records. AB - The content of treatment records is irrelevant if it cannot be understood. This is a report of a clinical audit project that aimed to assess the readability of records, and set standards to be maintained throughout the practice for handwriting and use of abbreviations. PMID- 11218533 TI - Transcultural oral health care: 3. Dental care and treatment during the fast of Ramadan. AB - The aim of this paper is to highlight issues that may affect dental treatment and care of Muslim patients when they are fasting during Ramadan. Recommendations are provided on how to provide culturally sensitive oral health care for this community. By taking into account the beliefs and wishes of the individual, dentists will provide a service that is acceptable and appropriate to both the Muslim community and individual Muslims. PMID- 11218532 TI - Current practice in endodontics: 2. Diagnosis and treatment planning. AB - The aim of this series of six articles is to improve the quality of endodontic treatment in general dental practice by considering what is currently being taught in dental schools. This second article considers the accurate diagnosis of endodontic lesions, which frequently present as emergencies requiring prompt, rapid and efficient attention. The paper then presents the treatment normally indicated once a correct and accurate diagnosis has been made. PMID- 11218534 TI - A case of sialolithiasis in a young female patient. AB - This paper describes the examination, diagnosis and treatment of a swelling that appeared in the floor of the mouth of a healthy 15-year-old girl. A sialith (stone) is not the first thing one considers when dealing with oral swellings in childhood but it does occur. Theories for its formation are described, as are the radiographic and clinical details of the case. PMID- 11218535 TI - A chemomechanical method for caries removal. AB - Over recent years the dental profession has shifted towards practising preventive dentistry and adopting more conservative and tooth-preserving procedures. Such progression is considered to be a response to the decline in the level of dental caries and advances in materials science. This shift in caries management will no doubt continue over the coming decades, based on rational clinical and scientific principles. Chemomechanical caries removal involves the application of a solution that selectively softens the carious dentine, thus facilitating its removal. This limits the removal of sound tooth structure, the cutting of open dentinal tubules, pulpal irritation and pain compared with conventional mechanical methods. PMID- 11218536 TI - The role of the general dental practitioner in detection and prevention of oral cancer: a review of the literature. AB - Over the last two decades little progress appears to have been made in reducing the incidence and number of deaths associated with oral cancer. The most recently available Scottish data indicate a steady rise in both incidence of, and mortality rates from, tongue and 'mouth' cancer, supporting previous observations of a steady rise in the incidence of oral cancer since the mid 1970s. Very little improvement in 5-year survival rates for oral cancer has been observed in England and Wales and, over the last 30 years, survival rates in Scotland have actually declined. Although many dentists are committed to examining the mouth for oral cancer, the majority still feel uncomfortable with involvement in patient education. Clearly scope exists for dental practitioners to improve patient awareness of both oral cancer itself and the risk factors associated with the disease. Dental teams should be aware of the opportunities within dental practice to contribute to preventive initiatives--such as smoking cessation. PMID- 11218537 TI - Enamel microabrasion. PMID- 11218538 TI - The occlusal management of maxillary anterior single-unit implant-supported restorations. PMID- 11218539 TI - AIDS and STD knowledge, condom use and HIV/STD infection among female sex workers in Bali, Indonesia. AB - The objectives of this paper were to examine changes in AIDS/STD knowledge and behaviour from 1992-1998, current levels of STD infection and psychosocial and demographic determinants of condom use and STD infection among female sex workers. Data for the study were drawn from cross-sectional surveys of female sex workers conducted in 1992, 1994 and 1997-8. For each survey, women participated in a face-to-face interview in the brothel complexes. Survey questions included information on AIDS/STD knowledge, demographics, sexual history and psychosocial factors related to condom use. After the last survey, women were offered a vaginal exam for STD diagnosis and treatment. Sera were tested for HIV infection (anonymous, Elisa/Western blot) and syphilis (TYPHA, RPR). Cervical mucous was tested for chlamydia (LcX), gonorrhea (LCx), herpes (pcr) and HPV (pcr). Knowledge of AIDS and awareness of STDs has increased tremendously in this population since 1992. Reported condom use has also increased substantially (69.9%). Perceived susceptibility toward HIV infection remains low. Ineffective preventive strategies such as medication use continue to be common. HIV infection remains very low in this population (0.2%), although the prevalence of other STDs such as gonorrhea (60.5%), chlamydia (41.3%) and HPV (37.7%) were very high. STD knowledge and self-efficacy were significantly related to condom use as were the sex workers' perceived susceptibility to STD and HIV infection. Women with a larger number of partners were more likely to be infected with gonorrhea, chlamydia and HIV. Women who had come to Bali recently were more likely to be infected with HIV and gonorrhea. PMID- 11218540 TI - Psychosocial and economic aspects of HIV/AIDS and counselling of caretakers of HIV-infected children in Uganda. AB - The knowledge that her child is infected puts a heavy emotional burden on a mother. Despair or depression lead to difficulties in reacting to the options and advice given by health workers. The compliance of the mother also is largely dependent on her acceptance of the HIV status of the child. Additionally, the belief that the child might die any moment may cause her not to take proper care of the child anymore. Worries of the caretakers are frequently related to poverty. Counselling of caretakers at the health centre could and should be an important element in care for HIV-infected children. Psychological and material support and advice concerning HIV infection, proper childcare and material problems may empower the caretakers. This may lead to a better follow-up of the child by health care workers and to increased compliance of and better care by the caretaker, which will improve life and survival of an infected child. PMID- 11218542 TI - HIV/AIDS-related services for women and the rural community context. AB - Rural communities present a different context for HIV/AIDS than urban communities, particularly for women. Theory, research and care and prevention practices for women in urban contexts are not necessarily easily applied to women in rural communities. This paper identifies several important characteristics of the rural community context and discusses how they may impact the development of HIV/AIDS-related care and prevention services for women. A social ecological perspective, with its emphasis on the relationship between individual-level behaviour and experience and different levels of the social environment, is presented as a useful approach to the study of the HIV/AIDS care and prevention service needs of rural women. Finally, recommendations for research are provided, consistent with a social ecological perspective, that can address the current lack of information regarding rural women's HIV/AIDS care and prevention service needs. PMID- 11218541 TI - African and European HIV-positive women: psychological and psychosocial differences. AB - The objectives were to study and compare the psychosocial and psychopathological aspects of HIV infection in African and European HIV-positive women living in France. All women included were seen in a semi-structured interview to assess personal history, history of their HIV infection, social and family relationships, preoccupation with childbearing and concerns about HIV infection and its prognosis. The comparison of psychological and psychosocial factors between HIV-positive African and European women showed certain significant differences. The demographic characteristics did not differ, except for current professional activity, with more African women being unemployed. The medical aspects of the HIV infection were similar to those described in the literature for the two populations. The most interesting findings were on the disclosure of HIV-positive status to family and friends, with significantly more European women informing friends and family, and on the desire to have children, which was much greater in African women; while they already had significantly more children, they still wanted to have even more. All these differences emphasize the need to adapt medical and psychosocial care to gender and to the ethnic and cultural background of the person. PMID- 11218543 TI - Trauma, coping, and depression among women with HIV/AIDS in New York City. AB - Among 230 HIV-positive women in New York City, we examined the association of retrospective self-reports of sexual and physical abuse, current coping strategies and depressive symptomatology (CES-D scores). Results revealed a high prevalence of abuse in childhood (50%) and adulthood (68%); 7% reported physical assault or rape in the last 90 days. As expected, childhood abuse was significantly correlated with both adult and recent trauma, and each type of trauma correlated with CES-D scores. Childhood abuse also positively correlated with the frequency of current adaptive and avoidant coping strategies, although avoidant coping had a stronger (negative) association with CES-D scores. Hierarchical regression analyses revealed the association between childhood abuse and CES-D scores persisted even after controlling for relevant demographic variables, more recent trauma and coping strategies. Implications for improving the psychological functioning of women living with HIV/AIDS are discussed. PMID- 11218544 TI - Use of female controlled microbicidal products for HIV risk reduction. AB - Many over-the-counter microbicidal contraceptive methods reduce the risk of acquiring sexually transmitted diseases. This pilot project compared the use of female controlled barrier methods in an extremely high-risk population of low income drug abusing women following an intervention designed to promote HIV risk reduction and barrier use. An HIV transmission risk reduction interactive intervention emphasizing self-esteem, assertiveness and sexual negotiation was offered to 41 drug dependent women. Participants were randomly assigned to one of two conditions, a male and female condom condition or a male and female condom plus N-9 products (vaginal suppositories, film, gel) condition. Results from the three-month follow-up period suggest that there may be a synergistic effect of availability of multiple protective methods on the overall rate of protective behaviours. The use of the male condom for penile/vaginal sex increased from 19% at study entry to 27% during the three-month follow-up period. The total protected sexual episode rate, calculated to include use of the other protective barriers distributed, was 60%. Thus, the condom use rate was not found to decrease because of the availability of alternative methods of protection. Future research should address the use of microbicidal products to empower women to prevent STD/HIV transmission. PMID- 11218545 TI - Introducing the female condom through the public health sector: experiences from South Africa. AB - The successful implementation of new public health policy is influenced by provider preparedness and user acceptability of the new intervention. This paper describes the development and implementation of a participatory Training of Trainers (TOT) programme as a precursor to launch the South African government's female-initiated HIV prevention strategies in public health clinics. Three hundred peer-trainees from throughout South Africa were trained through a comprehensive, modular and interactive three-day workshop. The workshop content included: HIV/AIDS knowledge, beliefs and attitudes; values clarification regarding HIV infection and sexuality; sexual desensitization; 'hands-on' training in the use of and introduction of the female condom; and counselling, communication and programme planning skills. The TOT generated a cadre of knowledgeable health care workers for training others and provided a support structure at the service delivery level for ensuring potential users' access to the female condom within each province. Qualitative assessments of the training and trainer debriefing sessions suggest that the training was successful in increasing knowledge and promoting positive attitudes about female condoms. In addition, the expanded repertoire of problem-solving approaches left providers feeling confident about recommending this method to clients. PMID- 11218546 TI - A gender-specific intervention for at-risk women in the USA. AB - Women are the fastest growing group in the USA to become infected with HIV. Also, the mode of transmission is changing with heterosexual behaviour being the predominant source. As these changes occur, HIV infection becomes more common in women who have not typically been considered at high risk. This paper describes an intervention designed to decrease unsafe sexual encounters and to focus on a highly meaningful concern in the lives of these women: relationships with men. The sessions encouraged making decisions, choice, partner selection, sexual rights, refusal of any unwanted sex, female controlled methods and other elements of empowerment. An eight-session and a four-session curriculum were created to assess dose factors as well. PMID- 11218547 TI - Coping strategies and emotional wellbeing among HIV-infected men and women experiencing AIDS-related bereavement. AB - AIDS influences the psychological coping not only of the person with the disease but also those close to that individual. Following a death from AIDS, family members and friends may experience atypical bereavement. Bereavement coping challenges can be especially difficult and pronounced for persons who are themselves HIV-positive. The prevalence of AIDS-related bereavement and psychosocial predictors of grief severity were examined in an ethnically diverse sample of 199 HIV-infected men and women. Eighty per cent of HIV-positive respondents had experienced the loss of someone close to AIDS, the majority of whom had sustained multiple and repetitive losses. Two-thirds of the participants who had experienced an AIDS-related loss reported grief symptoms in the past month. Hierarchical regression analyses revealed that grief was most closely associated with emotional suppression and avoiding coping strategies, with residual variance related to depression. Interventions for AIDS-related bereavement that reduce distress and maladaptive ways of coping are needed in order to meet the secondary prevention needs of bereaved people living with HIV/AIDS. PMID- 11218548 TI - Counsellors' perspectives on the experience of providing HIV counselling in Kenya and Tanzania: the Voluntary HIV-1 Counselling and Testing Efficacy Study. AB - Demand for HIV counselling services is increasing in developing counties, but there have been few previous studies that describe counsellors' roles and experiences providing HIV-related counselling in developing countries. Such information can be used to better supervise and support counsellors and thereby improve counselling services. As a sub-study of the Voluntary Counseling and Testing Efficacy Study, we conducted focus groups and individual interviews with 11 counsellors and counselling supervisors providing HIV counselling services in Kenya and Tanzania. Counsellors told us that their jobs were both rewarding and stressful. In addition to their obligations in the counselling relationship (providing information, protecting confidentiality and being non-judgemental), they perceived pressure to provide information and be good role models in their communities. Additional stresses were related to external (economic and political) conditions, 'spillover' of HIV issues from their personal lives and providing counselling in a research setting. Counsellor stress might be reduced and their effectiveness and retention improved by (1) allowing work flexibility; (2) providing supportive, non-evaluative supervision; (3) offering alternatives to client behaviour change as the indication of counsellor performance; (4) acknowledging and educating about 'emotional labour' in counselling; (5) providing frequent information updates and intensive training; and (6) encouraging counsellor participation in the development of research protocols. PMID- 11218549 TI - Perceived support in newly registered HIV/AIDS clinic outpatients. AB - This study compares levels of perceived social support in newly registered outpatients attending an HIV/AIDS clinic to those reported in a reference sample of other ambulatory medical populations. Perceived availability of four types of functional support is assessed: tangible, affectionate, positive social interaction and emotional-informational. Other elements of patients' support networks that might be associated with perceived support are also examined. In general, functional support levels in the outpatient PHA population were found to be similar to those of the MOS-SSS reference sample. Patient factors including age, gender, family awareness of HIV/AIDS diagnosis, time elapsed since diagnosis, employment status, physical health indicators, antiretroviral treatment history and support network size showed no relationship to functional support. Network composition factors significantly associated with higher social support ratings included the presence of a partner (all dimensions of functional support) and a greater proportion of close friends as opposed to close family members (emotional-informational support). Requesters of clinic support services tended to exhibit lower emotional-informational support scores compared to non requesters. Implications for the provision of support services to people living with HIV/AIDS are discussed. PMID- 11218550 TI - Barriers to social support for persons living with HIV/AIDS. AB - The purpose of this study was to test a barrier theory of perceived social support to HIV-positive gay men. The proposed model was tested for friends and family separately in order to investigate the uniqueness each provided. In both models, it was hypothesized that the presence of barriers to social support (availability, intimacy and disclosure) diminished acquisition of social support. The influence of barriers on the relationship between social support and health outcome (i.e. depression, t-cell count) for both friend and family models was also investigated. In general, data from HIV-positive gay men support barrier theory premises for both family and friends. Implications for helping professionals and researchers are proposed. PMID- 11218551 TI - Relationships of perceived stress to coping, attachment and social support among HIV-positive persons. AB - The purpose of this study was to examine the relationships of coping, attachment style and perceived social support to perceived stress within a sample of HIV positive persons. Participants were 147 HIV-positive persons (80 men and 67 women). Multiple regression analysis was used to examine the relationships of the demographic variables, AIDS status, three coping styles, three attachment styles and perceived quality of general social support with total score on the Perceived Stress Scale (PSS). PSS score was significantly associated with less income, greater use of behavioural and emotional disengagement in coping with HIV/AIDS, and less secure and more anxious attachment styles. These results indicate that HIV-positive persons who experience the greatest stress in their daily lives are those with lower incomes, those who disengage behaviourally/emotionally in coping with their illness, and those who approach their interpersonal relationships in a less secure or more anxious style. PMID- 11218553 TI - WHO global AIDS statistics. PMID- 11218552 TI - Relationship between quality of life, social support and disease-related factors in HIV-infected persons in Venezuela. AB - This study examines the relationships among health-related quality of life (HRQL), social support, sociodemographic factors and disease-related factors in persons infected with the human immunodeficiency virus (HIV) living in Venezuela. A sample of 118 HIV-infected persons living in Caracas, Venezuela, was surveyed using a written questionnaire that included a Spanish translation of the Interpersonal Support Evaluation List (ISEL) developed for this study, the Medical Outcomes Study Short Form-36 (SF-36) and a symptom inventory. All three instruments showed good internal consistency reliability. Multiple regression analyses were used to model SF-36 sub-scale scores as a function of symptoms, social support, HIV-status and use of antiretroviral drugs. The models explained between 16 and 39% of the variance in the different HRQL domains. Controlling for other variables in the model, level of symptomatology was significantly associated with all HRQL domains except social functioning and role-emotional scores. Social support was significantly associated with all HRQL domains except physical functioning and bodily pain. The use of antiretroviral drugs was significantly associated with social functioning. The study indicates the importance of social support to the quality of life of HIV-infected individuals in this culture. PMID- 11218554 TI - The 2000 Frieda Fromm-Reichmann Lecture. The current relevance of Fromm Reichmann's works. PMID- 11218555 TI - Impoverished counterfactual thinking is associated with schizophrenia. AB - Counterfactual thoughts are mental representations of alternatives to past events. Recent research has shown counterfactual thinking to be a pervasive cognitive process in normal populations and has linked it to effective problem solving and decision-making. The present research demonstrates that counterfactual thinking is impaired in schizophrenia patients relative to normal control subjects; this impairment was evident using measures of counterfactual thoughts as well as counterfactual-derived inferences. Furthermore, this impoverished counterfactual thinking partly mediated impaired social functioning experienced by schizophrenia patients. Given the convergence of neuropsychological evidence showing counterfactual deficits in frontal lobe patients and the documented frontal deficits in schizophrenia patients, future studies investigating a specific relationship between counterfactual thinking and frontal lobe function in schizophrenia patients would be a logical next step in this line of research. PMID- 11218556 TI - Counterfactual thoughts about conterfactual thinking. PMID- 11218557 TI - Some reflections on social-cognitive research in schizophrenia. PMID- 11218558 TI - Forgiveness: toward an integration of theoretical models. AB - Studies on forgiveness have only recently emerged in the psychological literature. Despite evidence that forgiveness is associated with positive therapeutic outcomes, the concept has received little theoretical consideration in mainstream psychology. Existing definitions and models of forgiveness differ widely, and little attempt has been made to integrate these diverse approaches. Based on a review of the Medline and Psychlit databases, the present article evaluates current conceptualizations of forgiveness in the psychological literature. The values and limitations of each approach are discussed with reference to two case studies: a close interpersonal relationship and a human rights violation presented to the Truth and Reconciliation Commission in South Africa. A new theoretical model, integrating the most valuable aspects of existing approaches, is proposed. PMID- 11218560 TI - Cultural psychiatry and minority identities in Japan: a constructivist narrative approach to therapy. AB - Clinical work with minorities in Japan is a relatively new and rapidly growing field. An influx of migrants from the 1970s has required psychiatrists to work with culturally different patients, yet few are experienced or trained in this area. With an even more radical population change imminent, skills in working with people of diverse cultural backgrounds are becoming a pressing need. While psychiatry in Japan has long been concerned with culture, only very recently has this concern involved differences among Japanese. Psychotherapy with both new migrants and individuals from more traditional minority backgrounds involves issues of acculturation and identity. A clinical approach based on a theoretical orientation of constructivistic narrative therapy can be usefully applied to multicultural situations. A case is presented in which this approach is employed in assisting a Korean-Japanese youth to deal with identity struggles. PMID- 11218559 TI - Posttraumatic stress two years after the Oklahoma City bombing in youths geographically distant from the explosion. AB - This article describes Posttraumatic Stress Disorder (PTSD) symptomatology in 69 sixth-grade youths who resided within 100 miles of Oklahoma City at the time of the 1995 bombing of the Alfred P. Murrah Federal Building. These youths neither had any direct physical exposure nor personally knew anyone killed or injured in the explosion. A survey conducted two years after the bombing assessed exposure, PTSD symptoms, and functioning. PTSD symptom frequency was measured with the Impact of Event Scale--Revised. Our BCD criteria for defining PTSD caseness was modeled after DSM-IV B, C, and D criteria requiring one reexperiencing, three avoidance/numbing, and two arousal symptoms for diagnosis. Those who met our BCD criteria had significantly higher PTSD symptom scores than those who did not. Both increased mean PTSD symptom score and meeting our caseness definition were associated with increased functioning difficulties. Media exposure and indirect interpersonal exposure (having a friend who knew someone killed or injured) were significant predictors of symptomatology. These findings suggest that children geographically distant from disaster who have not directly experienced an interpersonal loss report PTSD symptoms and functional impairment associated with increased media exposure and indirect loss. PMID- 11218561 TI - VEOS in a six year old girl: premorbid state, onset, course and therapy. PMID- 11218562 TI - [Analysis of the proportion of women at different qualification levels in departments of human medicine in Germany]. AB - BACKGROUND AND OBJECTIVE: In Germany leadership positions in medicine are characterized by an almost complete lack of women. The goal of this study was to determine the representation of women among different career ranks during medical school, residency and academic advancement during the past 20 years. METHODS: The annual reports of the German Federal Statistic Office in Wiesbaden were checked for the numbers of medical students, dissertations, physicians, internists, fellows and trainees at universities, habilitations and professorships. RESULTS: Among medical students, final examination, dissertation, physicians, internists and trainees at universities a proportion of women can be found nowadays which is at a 15% higher percentage level than 20 years ago. Among assistant professors and habilitations at universities there is a very low proportion of women, which did increase only slightly from 5 to 10% during the past 20 years. Within the same period of time the total number of professors and the proportion of female professors were nearly unchanged. Reunification of East and West Germany led to an increase of the representation of women among all levels of qualification which is due to the much higher proportion of female physicians in the former GDR. CONCLUSIONS: The lack of women in leadership positions in medicine in Germany is not due to a general lack of women in medicine. Among all other career ranks the proportion of women increased by 15%. The completely unchanged number and composition of the professors during the past 20 years suggests that the lack of women among this professional group has to do with conservatism which is an inherent trait of university professors in Germany. PMID- 11218563 TI - [Frequency-dependent rise in absolute threshold during DDD-R stimulation- clinical consequences]. AB - HISTORY AND ADMISSION FINDINGS: A 65-year-old female patient had been supplied with a rate-adaptive DDD-R pacemaker system because of symptomatic sick sinus syndrome with insufficient rate increase one year ago (first implantation of a DDD-system had taken place 14 years ago). In addition she had coronary atherosclerosis without relevant haemodynamic changes. Now she was taken into hospital because of dizziness and dyspnoea on exertion, without loss of consciousness. The physical examination showed normal results concerning heart, lungs and vessels. INVESTIGATIONS: During pacemaker control a significant rate dependent stimulation threshold increase was found (stimulation rate 70-160/min). Similar results were seen in threshold measurements during operation as well as for the ventricular lead implanted in 1982, and for the new electrode just placed in the right ventricle. Several pacemaker controls within 6 months after implanting the new lead showed a significant increase in pacing threshold. TREATMENT AND COURSE: Because of a new rate-dependent increase of pacing threshold the implantation of a further ventricular lead became necessary. Again a rate dependent threshold increase during and immediately after surgery was detected. This time the programming of the pacemaker allowed a good safety interval because of a generally low stimulation threshold. CONCLUSIONS: This case report demonstrates a rate-dependent rise in threshold on DDD-R stimulation. It clearly shows that this rise occurred more often at high than at low rates of stimulation, but there were marked individual differences. There was no clear correlation between cycle length and the interval from implantation to the investigation. Further investigations including stimulation with various cycle lengths should be carried out in patients at high risk. Furthermore, the development of modern pacemaker systems with autocapture might help to solve this problem. PMID- 11218564 TI - [Fulminant course of falciparum malaria]. AB - HISTORY AND ADMISSION FINDINGS: A 57-year-old white man had been travelling in Kenya for vacation until 14 days before admission. Due to apprehension about side effects, the patient had refused any malaria prophylaxis. Ten days before admission he developed low grade temperatures and suffered from pain in the limbs, from nausea and vomiting. A new episode of tachyarrhythmia was diagnosed two days before admission and was treated by his general practitioner. Finally he was admitted to our hospital because of high temperatures, chills and progressive clinical deterioration. Autopsy revealed prominent congestion of liver, spleen and cerebral vessels as well as subdural and subarachnoidal hemorrhage. INVESTIGATIONS: In both thin and thick peripheral blood smears Plasmodium parasites were demonstrated in approximately 30% of the eryhthrocytes and the diagnosis of Plasmodium falciparum was immediately confirmed by an immunological test. TREATMENT AND COURSE: Due to the fulminant clinical and neurological deterioration with progressive hypoxaemia, the patient required ventilator therapy already one hour after admission. Therapy with chinine and doxycycline was initiated and exchange transfusion was considered. However, due to hyperkalaemia and cardiac arrest, the patient died 4 hours after admission due to parasitic hemolysis. CONCLUSIONS: Severe Plasmodium falciparum infection in non immunized patients is a medical emergency and requires immediate diagnosis and treatment. Malaria should always be considered in the differential diagnosis in persons who have travelled to endemic areas and presenting not only with temperatures, but also with non-specific clinical signs, like cardiac arrhythmias. Although never entirely effective, chemoprophylaxis is highly recommended. PMID- 11218565 TI - [Diagnostic significance of autoantibodies in bullous dermatoses]. PMID- 11218566 TI - [Meaningful and meaningless hygienic measures in internal medicine]. PMID- 11218567 TI - [Venous catheter-associated infections in patients with neutropenia]. PMID- 11218569 TI - [Subcutaneous magnesium pump in a patient with combined magnesium transport defect]. PMID- 11218568 TI - [Aortic rupture in idiopathic Gsell-Erdheim medionecrosis]. PMID- 11218570 TI - [BSE (bovine spongiform encephalopathy) and the new variant of Creutzfeldt-Jakob disease]. PMID- 11218571 TI - Synthesis and immunotropic properties of 5-substituted 1,5-benzodiazepin-2-ones derivatives in cultures of human peripheral blood cells, Part III. AB - The reaction of 4-methyl-(A) and 3-methyl-1H-2,3,4,5-tetrahydro-1,5-benzodiazepin 2-one (B) with selected alpha,beta-unsaturated acid chlorides: crotonoyl, cinnamoyl, and 4-nitrocinnamoyl is described. We have also characterized immunotropic activities of these compounds in the proliferative response of human lymphocytes to phytohemagglutinin A (PHA) or to allogeneic cells in one-way mixed lymphocyte reaction (MLR), as well as their action on tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) production in peripheral blood mononuclear cells (PBMC) and mixed lymphocyte cultures (MLC). Some of the compounds exhibited regulatory activities in the proliferative response of cells to PHA depending on the reactivity of cells to PHA. The MLR induced proliferation of lymphocytes was moderately inhibited by two selected compounds. The compounds showed also inhibitor properties with regard to lipopolysaccharide (LPS)- and MLR-induced TNF alpha production. Structure-activity relationship was discussed. PMID- 11218572 TI - Synthesis and antinociceptive activity of (2-benzazolon-3-yl)propionamide derivatives. AB - The syntheses of (2-benzothiazolinon-3-yl)propionamide and (2-benzoxazolinon-3 yl)propionamide derivatives are reported. The structures of these compounds are elucidated by their IR and 1H-NMR spectral data, as well as by elemental analysis. The compounds were tested for antinociceptive activity by hot plate, tail flick, tail clip, and modified Koster tests. Compounds 6b and 7d were found to be the most promising compounds among the substances investigated. PMID- 11218573 TI - Synthesis of 5-substituted pyrrolo[1,2-b]pyridazines with antioxidant properties. AB - 5-Substituted pyrrolo[1,2-b]pyridazines have been prepared by cyclisation of pyridazine with diphenylcyclopropenone followed by further functionalisations in the pyrrolo[1,2-b]pyridazine 5-position. Several compound exhibit profound inhibition of lipid peroxidation in vitro. Lipid peroxidation of boiled rat liver microsomes was induced by ascorbic acid/FeSO4 and the peroxidation was determined by measuring the thiobarbituric acid reactive material. PMID- 11218574 TI - Benzolactam derivatives and their affinity for alpha 1- and alpha 2 adrenoreceptors. AB - A series of benzolactam derivatives has been evaluated for their affinity for alpha 1 and alpha 2-adrenoreceptors. The influence of terminal amine and amide fragments on the affinity and selectivity has been investigated. It has been found that derivatives containing 1,2,3,4-tetrahydroisoquinoline (THIQ) as the basic component can form potent alpha 1 and/or alpha 2 ligands, and that their alpha 1/alpha 2 selectivity depends on the benzolactam fragment. PMID- 11218575 TI - Studies on the structural variations of pentosan polysulfate sodium (NaPPS) from different sources by capillary electrophoresis. AB - Commercial pentosan polysulfate sodium salts (NaPPS) are highly sulfated polysaccharides derived from beechwood hemicellulose by sulfate esterification with a Mrel range of 1500-6000. The polysaccharide backbone of NaPPS consists of repeating linear units of 1-4 linked beta-D-xylopyranose with laterally substituted 4-methylglucopyranosyluronic acid units glycosidically linked to the 2 position of the main chain at every 10th xylopyranose unit on average. For many years NaPPS has been used for antithrombotic prophylaxis in Europe and interstitial cystitis in the USA and Australia. More recently NaPPS has found veterinary application for the treatment of osteoarthritis and related conditions in domestic animals and is registered for this use in Australia, New Zealand, Canada, UK, Eire, and several Scandanavian countries. At present the use of NaPPS for human disorders is confined to material manufactured by one company. However, for veterinary applications, NaPPS from three manufactures have been described. Since it is well known that the biological activities of sulfated polysaccharides are dependent on their molecular structures we considered it important to characterise these various NaPPS preparations using an established method of analysis. Unfortunately, traditional analytical techniques such as TLC, OR, UV/Vis spectroscopy, and size exclusion chromatography were incapable of providing structural information which would distinguish these NaPPS preparations from each other. In contrast, a capillary zone electrophoresis (CZE) method facilitated characterisation of the different NaPPS by a highly reproducible fingerprint, using a benzene-1,2,4-tricarboxylic acid buffer (8.75 mmol/L, pH = 4.9) with indirect UV detection (lambda = 217 nm) and a special capillary pre treatment (1 M NaOH for 1 h at 25 degrees C, then running buffer for 120 min at 25 degrees C applying -20 kV). In the present study more than 20 batches of NaPPS from the three manufacturers have been investigated and compared. Minor batch variations were observed to exist for each manufacturer's product however significant differences were detected between NaPPS synthesised by the different manufacturers. Moreover, some preparations showed fingerprint profiles that indicated a more heterogeneous mixture, probably containing other polysaccharides as well. PMID- 11218576 TI - Synthesis and antiproliferative activity in vitro of novel 1,5-benzodiazepines. Part II. AB - The reaction of 2,2,4-trimethyl-1H-2,3-dihydro-1,5-benzodiazepine (1) with cinnamoyl chloride leading to the formation of 1-cinnamoyl derivative 2 is described. Two novel benzodiazepines, 2,2,4-trimethyl-1H-2,3,4,5-tetrahydro-1,5 benzodiazepine (3) and 1-cinnamoyl-2,2,4-trimethyl-1H-2,3,4,5-tetrahydro-1,5 benzodiazepine (4), were synthesized by the reduction of 1 and 2 using NaBH4 in i PrOH and two other derivatives 5 and 6 were obtained by reaction of 4 with equimolar and dimolar quantity of cinnamoyl chloride, respectively. The structures of 1-6 were confirmed by analytical and spectral data (IR, 1H NMR, and MS). 7-Carboxy-2,2,4-trimethyl-1H-2,3-dihydro-1,5-benzodiazepine (7) was synthesized and its crystals were subjected to X-ray analysis. Benzodiazepines 1 6 were evaluated for antiproliferative activity in vitro. Among the compounds tested, 4-6 exhibited cytotoxic activity against human cancer cell lines, namely SW707 (colon cancer), MCF-7 (breast cancer), A549 (lung cancer), and HCV29T (bladder cancer). PMID- 11218577 TI - [Lysis of atrial thrombus with in situ injection of rt-PA]. PMID- 11218578 TI - [Management of gastroesophageal reflux in children with severe encephalopathy]. PMID- 11218579 TI - [Is the motivation to use dangerous drugs associated with the number of drugs used? Survey among 840 adolescent students]. PMID- 11218580 TI - [Sexually transmitted diseases in young children in Lome (Togo). Role of sexual abuse]. AB - OBJECTIVE: The purpose of this study was to determine the importance of sexual abuse in young children with sexually transmitted diseases (STD) in Lome (Togo). METHODS: This transversal study consisted of documenting all cases of STD in young children (up to 11 years of age) diagnosed during 20 months (May 1997 to December 1998) in the dermatovenereology unit of the Lome teaching hospital. Syphilitic (TPHA-VDRL) and HIV serologies were carried out in all children. These serologies were repeated two weeks and three months later in sexually abused children. RESULTS: During this period, 33 cases of STD were diagnosed. There were 16 cases of anogenital warts (13 females, three males; mean age: 5.6 +/- 2.4 years); 13 cases of gonorrhoea (all were females; mean age: 7.2 +/- 1.8 years); and four cases of genital trichomoniasis (four females; mean age: 6.2 years). In 12 of 13 cases of gonorrhoea, sexual abuse was noted with identification of the alleged contaminators in ten cases. In eight of 16 cases of anogenital warts (all observed in females; mean age: 6.1 +/- 1.9 years), and two of four cases of genital trichomoniasis (mean age: six years) sexual abuse was observed. Syphilitic serology was negative in all children, but one ten-year-old girl had HIV infection with identification of the alleged contaminator. CONCLUSION: The results of this study confirm that sexual abuse in children is not uncommon in black Africa and that the STD, like condylomata acuminata and gonorrhoea, are good indicators of this phenomenon. The classical consequences of such sexual abuses are aggravated in Africa by the high prevalence of HIV infection observed in the majority of countries, mainly in urban areas. PMID- 11218581 TI - [Early cardiovascular effects of corticotherapy for bronchopulmonary dysplasia]. AB - OBJECTIVES: The aim of this study was to analyze the time course of cardiovascular effects in glucocorticoid-treated premature infants with bronchopulmonary dysplasia (BPD). METHODS: In a retrospective case study, 63 ventilator-dependent very-low-birth-weight neonates (mean gestational age = 27.9 +/- 2 weeks and mean birth weight = 920 +/- 275 g) treated with dexamethasone (52%) or betamethasone (48%) were studied. The average value for each study day was calculated for systolic arterial blood pressure and heart rate. RESULTS: At initiation of treatment, blood pressures increased significantly from pre treatment to day 1 and continued to increase during the first week: as a percentage of pre-treatment baseline the mean increase for systolic arterial blood pressure was 19% (95% confidence interval [CI] = 16, 22) on day 2 (P < 0.001). The maximum amplitude of variation was observed before day 2 for 75% of the study group. As a group as a whole, the heart rate value significantly decreased on day 1 (mean difference = -14.6 beats/min; 95% CI = -16.5, -12.6; P < 0.001), and then reached pre-treatment value within one week. Cardiovascular response was independent of gestational age, birth weight and postnatal age at the beginning of treatment. CONCLUSION: During postnatal steroid therapy a rise in blood pressure is a common side effect, but bradycardia is mentioned very occasionally. The present study shows a marked increase in blood pressure during the first 48 hours concomitant with a decrease in heart rate. The inverse relationship between systolic arterial blood pressure and heart rate suggests a baroreflex response. PMID- 11218582 TI - [Colonization by Ureaplasma urealyticum and chronic lung disease in premature newborn infants under 32 weeks of gestation]. AB - Colonization of the respiratory tract of premature newborn infants by genital mycoplasma is suspected to be associated with chronic lung disease. METHODS AND PATIENTS: We prospectively determined the prevalence of genital mycoplasma colonization with nasopharyngeal or endotracheal culture in preterm neonates younger than 32 weeks gestation and its possible association with the development of chronic lung disease in a prospective study. RESULTS: Fifty-nine infants were enrolled and 11 (19%) were colonized with Ureaplasma urealyticum. In the subgroup of 45 ventilated infants, seven of seven U. urealyticum-positive infants developed chronic pulmonary disease versus ten of 38 (26%) of U. urealyticum negative infants (relative risk [RR] = 3.8; 95% confidence interval [CI] 2.2 to 6.5, P < 0.001). U. urealyticum-colonized infants had a lower median birth weight (760 vs 1,083 g, P = 0.04), a lower gestational age (26 vs 28 weeks, P = 0.03), and a higher incidence of symptomatic patent ductus arteriosus (P = 0.03). These potential confounding factors may partially explain the association between U. urealyticum and chronic pulmonary disease. However, this association remained statistically significant when the analysis was restricted to infants with birth weight of 1,000 g or less (RR = 2.3; 95% CI 1.3 to 4, P = 0.02) or to infants with a patent ductus arteriosus (RR = 2; 95% CI 1.3 to 3.1, P = 0.02). CONCLUSION: Colonization with U. urealyticum in ventilated preterm neonates younger than 32 weeks gestation is a significant risk factor of developing chronic pulmonary disease. PMID- 11218583 TI - [Collagen gastritis, an unusual cause of anemia in children. Report of 2 cases]. AB - When a child presents a severe anemia or resistant to iron supplementation, an upper gastrointestinal endoscopy has to be realized to find special causes. CASE REPORTS: We report observations of two patients, respectively 11 and 12 years old, who were admitted to hospital for a severe microcytic, hypochromic, aregenerative anemia (hemoglobin less than 50 g/L) due to an iron deficiency. The two children's history did not reveal a deficient diet, gastrointestinal tract disorder, ingested toxic or gastrotoxic drugs, or exteriorized hemorrhage. Upper gastrointestinal endoscopy showed a macroscopic pattern of gastritis. The stomach biopsies revealed subepithelial collagenous deposits. CONCLUSION: The collagenous gastritis involves lesions similar to those described in the small intestine (collagenous sprue) and colon (collagenous colitis). The pathogenic factors of the three entities are presently unknown, but they are often associated with autoimmune pathology. These two observations are the third and the fourth pediatric cases described. PMID- 11218584 TI - [Acute rhabdomyolysis disclosing polymyositis in children]. AB - Traumatic and non-traumatic rhabdomyolysis have been mostly reported in adults. Polymyositis rarely leads to rhabdomyolysis. CASE REPORT: We report the case of a 13-year-old girl with rhabdomyolysis. Full recovery was observed after symptomatic treatment. Nine months later she developed polymyositis. CONCLUSION: Long-term follow-up is necessary for rhabdomyolysis, even in those cases with an isolated occurrence caused by viral infection. PMID- 11218585 TI - [Esophageal duplication in children. Report of 7 cases]. AB - Esophageal duplications represent 10 to 20% of esophageal malformations and 15 to 20% of digestive duplications. METHODS: The authors report a series of seven cases observed between 1985 and 1999. RESULTS: The sex ratio was 2.5. The diagnosis was made before the age of six months in five cases. The clinical presentation included respiratory signs in six cases and digestive signs in five cases. The diagnosis was made on the association of a mediastinal mass behind vertebral malformation in five cases. The duplication was cystic in five cases and tubular in two. A perforation in the pleura occurred in one case of tubular duplication. The intervention consisted of total excision of the duplication in four cases and subtotal resection in two cases. For the seventh patient, who presented a perforation of the duplication in the pleura, the operation comprised a thoracic drainage associated to feeding gastrostomy. The histologic examination of the six operative specimens confirmed the diagnosis of esophageal duplication. Six patients survived and have favorable evolution with an average follow-up of four years. DISCUSSION: Esophageal duplications represent 15 to 20% of digestive duplications. Their clinical presentations are variable. Their diagnosis is often made before the age of two years, when a posterior mediastinal mass is associated with vertebral malformations. Apart from the tubular form, which is rare, diagnosis is confirmed by the histologic study of the operative specimen. CONCLUSION: Esophageal duplications are rare and often pose a problem of positive diagnosis. Their treatment is surgical and should be undertaken before the appearance of complications. PMID- 11218587 TI - [Breastfeeding and hepatitis C virus (HCV): the need for a careful appraisal]. AB - We review the available data on the possible role of breast-feeding in hepatitis C virus (HCV) transmission to infants of HCV-RNA-positive mothers. Current knowledge about HCV excretion through breast milk, HCV infection of breast-fed infants by mothers contaminated after delivery, and vertical transmission risk to infants breast-fed by chronic HCV viremic mothers are presented. Vertical transmission risk by breast-feeding HCV-RNA-positive mothers is unclear: no study has been performed with the aim and the required methodology to evaluate HCV transmission risk related to breast-feeding duration. Recommendations to HCV-RNA positive mothers who wish to breast-feed their infant are discussed in light of present knowledge about HCV secretion in breast milk, mother-to-infant HCV transmission, and historical records on vertical transmission of other viruses to infants breast-fed by their viremic mothers. PMID- 11218586 TI - [Anemia and limping in a vegetarian adolescent]. AB - A vegan diet in the child and adolescent can induce severe bone sequelae by rickets and osteomalacia and megaloblastic anemia by cobalamin deficiency. CASE REPORT: A 15-year-old adolescent was hospitalized because of lameness and pallor. The lameness was explained by femoral epiphysiolysis caused by rickets with severe hypocalcemia. The pallor, jaundice and splenomegalia were due to cobalamin deficiency megaloblastic anemia. A prolonged supplemental diet with calcium, vitamins D and B12 as well as orthopedic treatment stabilized the bone lesions. The megaloblastic anemia was cured by parenteral cobalamin. The adolescent and his brother were victims of a diet imposed by a cult and a lack of care due to their parents refusing that a vegan diet was the cause of the deficient pathology. Penal proceedings led to the incarceration of the parents and to the placement of the children. COMMENTS: Deficiencies in calcium and vitamins D and B12 may be severe in a child's development with a vegan diet. This case report reveals the social and legal problems of an inappropriate diet in infancy imposed by parents who are followers of a fundamentalist church. Beyond the management of children in cults, health professionals have to prevent, screen and supplement the deficient diet. PMID- 11218588 TI - [Obesity in children: a disease that risks the vital prognosis]. AB - Drug consumption by adolescents causes social and health problem. OBJECTIVE: This prospective study was designed to examine reasons for and against using substances such as tobacco, alcohol, and marijuana and to discover whether or not motives to use drugs vary with the number of drugs used. METHOD: The participants were 886 adolescents from a suburban high school (Nancy, France), who answered a self-report questionnaire. RESULTS: The response rate was 95% (655 males and 175 females, mean age 17.5 +/- 2.5 years). The prevalence of current tobacco use, former tobacco use and never used was 40.7, 21.3 and 31.7%, respectively. For alcohol consumption, the results wre 85.8, 3.5 and 0.7% respectively and for marijuana consumption 34.4, 18.3 and 47.3%, respectively. Ecstasy had already been used by the respondens. The main reasons given by the adolescents to explain why they did or did not use these substances varied with the mumber of drugs used. CONCLUSION: This work shows an increasing deterioration of youths' social relations (with his/her parents and with him/herself) that seem to depend onthe number of drugs used. Further research is necessary to improve these results. PMID- 11218589 TI - [Home artificial nutrition in children. Indications and organization]. AB - Home enteral and parenteral nutritions are logical alternatives to long-term hospitalization when a long-term nutritional support is required. They are effective and safe methods, compatible with a good quality of life. Major cost savings have been demonstrated as a result of home nutrition rather than hospitalization. Nevertheless, one must not underestimate the importance of the families' teaching and the medical follow-up to prevent somatic and psychological complications. The quality of home nutrition programmes depends on the organization of the nutrition support teams based on close collaboration between the various involved professionals. PMID- 11218590 TI - [Identification of language disorders in children. A contribution to the prevention of illiteracy]. AB - Early identification of disorders of oral and written language development is essential for effective action before the vicious circle of educational failure and established psychosocial consequences. There has been growing awareness among health and education professionals that the means of recognizing, treating and teaching children with specific oral and written language disorders are inadequate. There is still a limited number of diagnostic tools that have not been fully evaluated. Nevertheless, considerable effort has been made in recent years to develop instruments for early detection and precise diagnostic evaluation. Developments in cognitive neuropsychology provide new approaches for the management of these disorders. PMID- 11218592 TI - Allergic to dentistry? PMID- 11218591 TI - [Jargon of the neonatal intensive care unit]. AB - Jargon, the specialized vocabulary and idioms, is frequently used by people of the same work or profession. The neonatal intensive care unit (NICU) makes no exception to this. As a matter of fact, NICU is one place where jargon is constantly developing in parallel with the evolution of techniques and treatments. The use of jargon within the NICU is very practical for those who work in these units. However, this jargon is frequently used by neonatologists in medical reports or other kinds of communication with unspecialized physicians. Even if part of the specialized vocabulary can be decoded by physicians not working in the NICU, they do not always know the exact place that these techniques or treatments have in the management of their patients. The aim of this article is to describe the most frequent jargon terms used in the French NICU and to give up-to-date information on the importance of the techniques or treatments that they describe. PMID- 11218593 TI - The NHS dental plan--key points for the busy practitioner. PMID- 11218594 TI - Osteogenic distraction within the craniofacial complex. AB - Osteogenic distraction is a method of increasing bone length, and was developed by orthopaedic surgeons. It is now being used in the craniofacial region. This paper outlines some of the suggested uses: mandibular distraction can be used to correct hypoplasia and asymmetry in both children and adults; maxillary distraction can bring the midface forward, and holds potential for people with cleft lip and palate; augmentation of alveolar ridges and regeneration of mandibular tissue following tumour resection show considerable promise. The complex spatial dimensions of the craniofacial bones present considerable challenges for this developing technique. PMID- 11218596 TI - Current practice in endodontics: 3. Access is success, and rubber dam is easy. AB - The prime aim of this series of articles is to improve the quality of endodontic treatment in general dental practice by considering what is currently being taught in dental schools. This, the third article, offers guidance and hints to ease the use of rubber dam, which should be mandatory for root canal therapy. It also considers the shape, position and extent of access cavities. The access cavity can make all the difference in success or failure of endodontic treatment. PMID- 11218595 TI - Allergy to a common component of resin-bonding systems: a case report. AB - Allergies to materials routinely used in dentistry are becoming more prevalent. The hydrophilic resin 2-hydroxyethyl methacrylate is a common constituent of systems designed to bond resin-based restorative materials to dentine. It has been considered to have a high sensitizing potential, although dental patient related allergies to the resin appear to be rare. This report presents details of a patient who has such an allergy, which, it is suspected, manifested as an intra oral lichenoid reaction to the closely approximating anterior restorations. PMID- 11218597 TI - Fibre-reinforced materials. AB - This paper considers the role of fibres in the reinforcement of composite materials, and the significance of the form the fibre takes and the material from which it is made. The current dental applications of fibre reinforcement, including dental cements and splints, fibres made into structures for use in composites, denture bases and the contemporary use of fibres in fixed partial dentures, are reviewed. Their role in biomedical implants is surveyed and their future forecast. PMID- 11218598 TI - Transcultural oral health care: 4. Dental medication for Muslim patients. AB - The aim of this paper is to provide a guide for general dental practitioners who may need to prescribe medication to Muslim patients, particularly during the month of Ramadan. An understanding and appreciation of the patient's religious background will aid treatment compliance and allow dentists to provide a culturally sensitive service for their Muslim patients. Drug therapy compliance is important, but it is likely to be poor among Muslim patients during the month of Ramadan, when fasting and religious practices may cause problems. The authors provide guidelines on good clinical practice and prescribing regimens for general dental practitioners treating Muslim patients, particularly during Ramadan. PMID- 11218600 TI - Adapting crown preparations to adhesive materials. AB - Traditional approaches to crown preparation for replacement crowns or teeth with short clinical crowns are often overly destructive of tooth tissue. Adhesive cements or composites combined with dentine bonding agents provide the clinician with some flexibility in treatment planning and should be considered when more destructive techniques would otherwise be necessary. PMID- 11218599 TI - The long-term management of patients with tooth surface loss treated using removable appliances. AB - The causes of tooth surface loss are multi-factorial and hence can be difficult to eradicate. This paper identifies the problems that may be anticipated during the long-term management of patients where tooth surface loss has been treated using removable appliances, where the number of teeth is often reduced. Wear and tear are inevitable and patients should therefore be made fully aware of the possibility of the gradual deterioration and failure of restorative work. Treatments should be planned, which would enable the dentist to recover the situation, with minimal inconvenience to the patient. PMID- 11218601 TI - Presenting the dental assisting professional in the year 2000. PMID- 11218602 TI - How to determine a fair & equitable salary for dental auxiliaries. PMID- 11218603 TI - Next patient please. PMID- 11218604 TI - Environmental surface disinfection. PMID- 11218605 TI - Lost dentists. PMID- 11218606 TI - The York review of water fluoridation--key points for the busy practitioner. PMID- 11218607 TI - The Cartwright Prize. Caries removal and the pulpo-dentinal complex. PMID- 11218609 TI - Current practice in endodontics: 4. A review of techniques for canal preparation. AB - The prime aim of this series is to improve the quality of endodontic treatment in general dental practice by considering what is currently being taught in dental schools. This article reviews the development of today's endodontic techniques and suggests alternative methods of obtaining a clean and shaped canal, in keeping with the varying requirements of practitioners of differing backgrounds and abilities, while keeping in mind the established aims and objectives of endodontic treatment. PMID- 11218608 TI - Strength of a 'no-bottle' adhesive system bonded to enamel and dentine. AB - Existing bonding systems permit effective bonding to enamel or dentine. Bonding to dentine is mainly achieved through the hybridization of dentine with resin. However, despite their success, the 'three-bottle' systems do have drawbacks--the large number of steps involved may be confusing and prone to errors of application, as well as being time consuming. Recently developed systems have significantly reduced the number of steps and the total treatment time, but deliver a reliable outcome. PMID- 11218610 TI - Multiple Stafne bone cavities: a diagnostic dilemma. AB - Salivary gland inclusions in the mandible are relatively uncommon. If defects occur they are generally unilateral, although bilateral cases have been reported. This article describes an unusual case in which the dental panoramic tomogram revealed three radiolucent areas in the mandible. The diagnosis of the two posterior radiolucencies was confirmed as Stafne's bone cavities but a definite diagnosis for the parasymphyseal lesion remained elusive, even after surgery. However, Stafne's bone cavities are known to occur in this region and this diagnosis remains the most probable. PMID- 11218612 TI - Rhinoliths presenting during routine radiography: two cases. AB - Rhinoliths are calcified masses found within the nasal cavity. They are an uncommon finding and usually present to ENT surgeons. This article presents two cases where rhinoliths have been recognized in the dental setting, and discusses their management and treatment. PMID- 11218611 TI - Transcultural oral health care: 5. Diet and minority ethnic groups in the United Kingdom. AB - Dietary behaviours of minority ethnic groups vary considerably, not only between groups but also within communities and families. The aim of this article is to consider the information on diet and eating habits of members of minority ethnic groups, especially with regard to sugar consumption. PMID- 11218613 TI - The early management of Class III malocclusions using protraction headgear. AB - Class III malocclusions affect approximately 3% of Caucasians. Treatment options include; growth modification, dental camouflage and, once growth has ceased, orthognathic surgery. Originally, Class III malocclusions were thought to arise primarily from an overdevelopment of the mandible, but it is now known that maxillary retrusion contributes in up to 60% of cases. Maxillary retrusion is best treated with a combination of protraction headgear and rapid maxillary expansion, preferably before the age of 9 years. This article provides an overview of the management of skeletal Class III cases using protraction headgear with particular guidance for the general dental practitioner on when and how to treat. PMID- 11218614 TI - Immediate auto-bridge. PMID- 11218615 TI - Caution with oral midazolam. PMID- 11218616 TI - Dentine caries: take it or leave it? PMID- 11218617 TI - Transcultural oral health care and the Chinese. PMID- 11218618 TI - Transcultural oral health care of the Chinese. PMID- 11218619 TI - Long-term relapses of breast cancer: questions, interpretations and hypotheses. AB - The author has demonstrated in previous publications that the consistent characteristic of long-term relapses of carcinoma after more than 8 years from surgery is hormone dependence, since long-term relapses occur almost exclusively in hormone-dependent tumors such as carcinoma of the breast, prostate, endometrium and thyroid. Such publications presented a series of 237 long term relapses of breast cancer that occurred at no less than 8 years from the mastectomy, which proved that all the patients were estrogen-receptor positive. Estrogen-negative cases who did not relapse after 8 years from surgery should be considered cured, as is found for cases of non-hormone-dependent tumors. Therefore, the study demonstrates that breast cancer, without the presence of hormone receptors (which influence clinical behavior) is similar to neoplasms that arise in all parts of the body. The author herein presents a personal hypothesis relative to the possibility that the presence of receptors indirectly conditions the formation of antimitotic factors up to determining in some cases the phenomenon of long-term relapses. Such factors are presumably physiological, and the possibility that such a hypothesis can also serve to explain the results obtained with hormone therapy of breast cancer is examined. PMID- 11218620 TI - Peripheral neuropathy without cryoglobulinemia in patients with hepatitis C virus infection. AB - BACKGROUND: An association between essential mixed cryoglobulinemia and hepatitis C virus infection has been documented by many reports. Some clinical manifestations such as purpura, arthralgia, vascular lesions and peripheral neuropathies are also connected with the presence of detectable cryoglobulins. The association between HCV infection, the presence of mixed cryoglobulinemia and peripheral neuropathy is well documented. The aim of this study was to define the possible presence of peripheral neuropathy in HCV patients without detectable cryoglobulins and the possible association with the different genotypes. METHODS: Twenty patients (11 females, 9 males) with chronic HCV hepatitis and without detectable cryoglobulins were submitted to neurological and electrophysiological studies to detect a possible peripheral neurological involvement. In all patients the HCV infection was assumed by the presence of antibodies to HCV with ELISA assay and then confirmed with recombinant immunoblot assay. HCV genotyping was obtained by INNO LIPA in 15 out of 20 patients. In 4 patients a sural nerve biopsy was possible. RESULTS: Genotype 1b was present in 80% of patients, while 1a in 13.3% and 4 in 6.6%. Thirteen patients had positive neurological anamnesis (65%), while neurological examination was positive in 40% of the cases. Electromyographic study was positive in 50% of subjects. The sural nerve biopsies agreed with axonal degeneration in amyelinated fibres. CONCLUSIONS: Our results suggest a possible peripheral neurological system involvement in patients with HCV infection without cryoglobulins. PMID- 11218621 TI - Role of monocytes in the early phase of acute myocardial infarction. AB - BACKGROUND: In acute myocardial infarction peripheral leucocytosis occurs early and fibrinogen levels increase in response to the tissue injury, expressed by the enhanced enzyme plasma levels. The aim of the present study has been to investigate if a unifying link between these modifications might be found. METHODS: In 325 patients, 246 men and 79 women, 61.46 +/- 11.00 and 70.03 +/- 11.30 years mean age respectively, at admission for myocardial infarction and before treatment, we simultaneously measured plasma fibrinogen (FBG), hemochromocytometric parameters and plasma enzyme aspartate and alanine transaminase (AST and ALT), lactate dehydrogenase (LDH) and creatine phosphokinase (CPK). The statistical analysis was performed by using standard multiple regression for dependent variable FBG and for the variables white blood cells (WBC), monocyte number, large unstained cells (LUC) and CPK. RESULTS: The results showed that FBG was significantly correlated with monocyte (p < 0.001) and LUC (p < 0.05) counts; assumed as dependent variable, further on with FBG, monocyte number was correlated with WBC count, LUC and CPK; further on with monocyte number, WBC with neutrophile and lymphocyte counts, LUC with CPK, CPK with LDH. CONCLUSIONS: The study seems to show that monocyte modifications occur already in the early phase of myocardial infarction. These modifications are directly related to damage extension, as deducible from CPK levels, and seem to mainly modulate FBG and WBC, since the cytokines and hematopoietic growth factors production by activated monocytes. PMID- 11218622 TI - Seroprevalence of Helicobacter pylori infection in a group of hospitalized geriatric patients. AB - BACKGROUND: In recent years several epidemiological surveys have reported the association between Helicobacter Pylori (HP), chronic ischemic heart disease (CHD) and cerebrovascular disease (CVD). None involved the geriatric population in which these diseases are prevalent. METHODS: We investigated the HP seropositivity prevalence in a group of over 75-year-old subjects recruited among all patients consecutively admitted for various diseases in an Internal Medicine Department during a period of 9 months. INTERVENTION: We measured HP IgG antibodies employing a commercially available kit based on reverse flow chromatography highly feasible and simple to perform and we investigated all patients for past or present CHD/CVD. RESULTS: From our data, the prevalence of seropositivity to Hp does not differ from other wider age stratified studies; more in detail; in the over 90-year-old patients we found the same HP seropositivity prevalence as in younger group but were not able to confirm the progressive lowering or seroprevalence in extreme geriatric age. CONCLUSIONS: No clear correlation between HP seroprevalence and CHD and CVD was found, but a link with CHD seems possible for the determinant (age) is common to both conditions. PMID- 11218623 TI - Association of alpha-interferon and acetyl cysteine in patients with chronic C hepatitis. AB - BACKGROUND: Numerous experimental findings have underlined the relationships between liver damage and production of oxygen-derived free radicals during inflammation. In chronic hepatitis C liver disease this damage may be attributed to altered oxide-reductive balance and glutathione (GSH) depletion. Moreover, it may be linked to chronic inflammation provoked by the replicative activity of the hepatitis C virus and its relationships with immune system cells. Our aim was to assess the effects of combined IFN + NAC treatment to compare the effects of interferon alpha-n1 associated with N-acetyl cysteine treatment with the results observed using interferon therapy alone. METHODS: EXPERIMENTAL DESIGN: prospective randomised study. SETTING: Ambulatory and hospitalised care. PATIENTS: 77 selected patients affected by chronic C hepatitis. INTERVENTIONS: our patients were investigated by laboratory tests (ALT values, RIBA test, HCV RNA, oxide-reductive balance), liver biopsy and liver US. The recruited subjects were treated with interferon and N-acetyl cysteine or with interferon alone. RESULTS: Our findings confirmed the presence of oxidative stress in patients with chronic hepatitis C and showed earlier relapse in patients treated with interferon alone. The difference between the results in patients treated with interferon and N-acetyl cysteine and those on interferon alone was significant. CONCLUSIONS: The good results and absence of side effects in patients treated with interferon + N-acetyl cysteine recommend wider use of this association. PMID- 11218624 TI - The use of intravenous immunoglobulin in sine causa or alloimmune recurrent spontaneous abortion (RSA). AB - BACKGROUND: Recurrent spontaneous abortion (RSA) has an incidence of 0.5%-1%. It is thought that immune reaction disorders in the mother may evolve in unexplained RSA, which has a higher incidence in women over 40 years old. METHODS: Twenty three patients with recurrent spontaneous abortion of unknown origin and two autoimmune cases were treated with intravenous specific immunoglobulins at the 5th-6th week of pregnancy and fifteen days later. RESULTS: After treatment, nineteen patients brought their pregnancy to term, five aborted, one is pregnant at present. CONCLUSIONS: The use of immunoglobulins seems to be efficacious in recurrent spontaneous abortion of unknown origin. Our results support the theory that this treatment is able to passively transfer the sparking off factor that allows the pregnancy to evolve. PMID- 11218625 TI - Azithromycin in the treatment of Plasmodium falciparum gametocytes. Preliminary observation. AB - BACKGROUND: Treatment of malaria represents a problem as antimalarial drugs are relatively few, and because of the increasing widespread resistance of Plasmodium falciparum to most of these drugs. A partial efficacy of azithromycin against Pl. falciparum hepatic stage and against trophozoytes in the erythrocytic stages of the disease has been demonstrated. No data concerning the activity against gametocytes are available, and primaquine stands as the only therapy against Pl. falciparum gametocytes. Primaquine causes haemolysis in patients with glucose-6 phosphate dehydrogenase (G6PD) deficiency, so primaquine therapy is usually avoided. A better tolerated therapy against gametocytes would be useful to reduce malaria transmission. We present the results of a study concerning the efficacy of azithromycin in the treatment of P. falciparum gametocytes. METHODS: A prospective study was performed: 4 patients with Pl. falciparum gametocytes (3 children, 1 adult) were treated with azithromycin for concomitant bacterial infections; in the meantime two children with gametocytes were taken as control. Azithromycin was administered as recommended. RESULTS: Gametocytes were detectable in children thick blood smears after 8, 5 and 6 days respectively after the beginning of azithromycin therapy, while they were undetectable in the adult thick blood smear 5 days after the beginning of the therapy. The gametocytes spontaneously disappeared in the two controls 4 to 6 days after the beginning of observation. CONCLUSIONS: These data suggest that azithromycin seems ineffective against Pl. falciparum gametocytes. Further studies are needed in order to determine whether azithromycin treated gametocytes are infective to mosquitoes or not, and to confirm this first observation. PMID- 11218626 TI - Local recurrences and primary surgery in rectal carcinoma. AB - BACKGROUND: The authors analyze retrospectively a consecutive series of rectal carcinomas operated on with different surgical strategies at Third Surgical Department of "La Sapienza" University of Rome, between January 1985 and December 1997, by one expert surgeon (GDM), and report the incidence of the local recurrence correlated to the surgical technique development. METHODS: In most recent groups of patients treated for extraperitoneal neoplasm from January 1992 with curative (R0) total mesorectal excision (TME) and nerve sparing technique (NST) (Group C, n = 47) and with curative TME plus lateral pelvic lymphadenectomy (LPL) and NST (Group D, n = 7), sacrificing the pelvic autonomic nervous system only in case of neoplastic infiltration, the local recurrence was 8.5% (4 cases, with mean interval of 30.5 months) and 0 respectively at mean follow-up of 44.9 and 55 months. RESULTS: In none of the local recurrences of the Group C a re resection (neither curative nor palliative) was possible and the survival was 50% at 14 months from the diagnosis of relapse. Instead, in local recurrences of rectal carcinoma in patients who underwent a first anterior resection with less extended dissection in other Department (Group E), a re-resection was possible for 3 cases out of 4 (R0, R1 and R2 operations); re-resected patients are now alive at mean follow-up of 33.6 months (82, 12 and 7 months, respectively). In Group A patients, treated between January 1985 and December 1988 with partial mesorectal excision (R0) also for extraperitoneal localization, the incidence of local relapses is 21.9% (9/41 cases) vs 11.2% (11/98 cases) in Group B patients, treated from January 1989 with curative TME for extraperitoneal tumors. CONCLUSIONS: The incidence of local recurrences of extraperitoneal rectal cancer can be reduced by total mesorectal excision. The total sparing of pelvic autonomic nervous system in advanced rectal carcinoma doesn't increase the incidence of local recurrences. PMID- 11218627 TI - Patient's needs in substitutive dialysis treatment. Some psycho-social and organizational considerations. AB - BACKGROUND: The observations here presented come from an action-research project carried out at the Dialysis Centre of Ivrea. The work is focused on the articulation between subjective (the felt experience) and objective variables (the structure and intervention typology) with the aim of understanding patient's needs from an organizational point of view. METHODS: A questionnaire to evaluate the needs of dialytic patients and the burden that these have on the health service and staff, was formulated by the nurses. RESULTS: The results showed how the patient's clinical history indicate, significantly, not only personal and subjective aspects (e.g. interpersonal relationships), but also how they construct their relationships with the hospital and its services (including the hospital staff). CONCLUSIONS: Data open up certain reflections on what role communication and information play within the hospital structure. Efficient communication contributes both to reduce the anxiety level and to improve the organizational climate therefore influencing service quality. PMID- 11218628 TI - Effects of acute normovolaemic haemodilution and partial exchange transfusion on blood product utilization, haemostasis and haemodynamics in surgery of the thoracoabdominal aorta. A cohort study in consecutive patients. AB - BACKGROUND: This paper outlines the technique of acute normovolaemic haemodilution with partial exchange transfusion (ANHPET) in surgery of the thoracic and thoracoabdominal aorta. Perioperative coagulation parameters and patterns of blood product utilization observed with this technique are described and compared with results for historical controls treated without ANHPET. METHODS: During thoracoabdominal aneurysm repair, acute normovolaemic haemodilution with partial exchange transfusion (ANHPET) was used to withdraw of up to 3 L of blood. This was returned to the patient at the end of the reconstruction. Albumin 5% and stored packed red cells (PRC) were used for replacement. Seven patients underwent surgery with ANHPET, and fifteen without. Univariate and multivariate analysis of variance was used to examine differences between these groups. RESULTS: No differences were observed between the two groups for estimated blood loss, PRC transfused, and postoperative haemoglobin concentration. The ANHPET group received fewer platelets (8 vs 22 units, p = 0.0004), cryoprecipitate (0 vs 13 units, p = 0.02), and desmopressin or epsilon aminocaproic acid (0 of 7 vs 4 of 15 patients, p = 0.04). FFP use was not significantly different (11 vs 17 units). Postoperatively, PTT values were less prolonged (26 vs 34 sec, p = 0.05) and platelet concentration higher (218 vs 169 x 109/L, p = 0.01) in the ANHPET group. A significant reduction in the total of blood products transfused was observed in the ANHPET group (30 vs 68 units, p = 0.003). Control of hypertension was facilitated by phlebotomy so that nitroglycerine was necessary in low doses only (0.25-1.0 microgram/kg/min). CONCLUSIONS: ANHPET reduced blood product transfusion, improved postoperative haemostatic parameters and simplified the management of cross-clamping hypertension. PMID- 11218630 TI - A new method of repair for quadriceps tendon ruptures. A case report. AB - Rupture of the quadriceps tendon is an uncommon injury observed predominantly in subjects over 40 years old. Multiple surgical techniques have been employed to repair fresh and neglected ruptures; methods that make use of allograft and augmentation with tissues harvested from around the knee have been reported. We describe a case of surgical repair of a tendon-bone junction rupture in a 64-year old patient by use of suture anchors to attach the tendon to bone and improve fixation of the soft tissue elements. Clinical diagnosis of rupture was confirmed radiographically and echographically. Surgical repair was performed within 24 hours of injury. Active movement of the knee started after 3 weeks and the patient was permitted to walk without weight-bearing with a knee cage. Three weeks later, he was permitted to walk with full weight-bearing unassisted by crutches; the knee cage was removed 6 weeks after surgery. At his most recent follow-up 24 months postoperative, quadriceps strength was equal to that of the controlateral knee and the patient has returned to sports and daily activities. The surgical method presented here provides a suture of the tendon ends without putting excess stress on the suture line during the period of early knee mobilization. Advantages over other techniques include reduced operative time, easy access to the implantation site, and better resistance of the suture material: the patient is thus able to initiate physical therapy earlier and more aggressively. PMID- 11218629 TI - Latex allergy. History, diagnosis and prevention. AB - During the past 10 years the incidence of natural rubber latex (NRL) allergy has dramatically increased. It occurs predominantly in certain high risk group: health care workers, latex industry workers, immune compromised individuals (such as children with spina bifida) and persons with positive risk factors (such as multiple surgeries). The epidemiology, history, mechanism, clinical symptoms and signs, and diagnosis of latex allergy are presented briefly. The subject of this review is to understand the importance in reducing the prevalence of latex allergy: reducing exposure, using appropriate work practices, training and educating workers, monitoring symptoms and substituting non latex products when appropriate. PMID- 11218631 TI - Bilo-pancreatic Ascaris Lumbricoides infestation. Endoscopic discovery and removal. AB - Ascaris Lumbricoides infestation is relatively rare in industrialized countries, and it occurs mainly in conditions in which hygiene is lacking. We describe here a case of a 39-year-old female from ex-Jugoslavia affected by recurrent hepatic colic. At entry ultrasonography revealed microlithiasis in the gallbladder and widening of the pancreatic head. The subsequent ERCP showed slight filling defects in the choledochus and an inflammation-like stricture of the papilla of Vater, and after endoscopic sphincterotomy we saw an outflow of dense bile and microlitholits. Thus, a standard surgical cholecystectomy was carried out and the patient was dismissed on the 3rd postoperative day without any symptoms. However, the patient was admitted again after four days for a new coliky pain attack. An upper endoscopy showed a 23 cm long mobile parasite in the duodenum: it was caught with the polypectomy loap, extracted and identified as A. Lumbricoides. The patient's symptoms disappeared after the endoscopic removal of the worm and she was dismissed the day after the worm's removal. No recurrence of symptoms was noted during a 1-year follow-up. This case showed that A. Lumbricoides infestation of the biliary tree should be considered when biliary and/or pancreatic symptoms recur, especially in patients coming from undeveloped countries. At the same time we showed that endoscopic removal is a safe and effective treatment for this infestation. PMID- 11218632 TI - Micrococcus luteus: a putative cause of hepatic abscess? AB - Micrococcus luteus was repeatedly isolated in blood cultures during a prolonged feverish syndrome in a patient who presented with multiple hepatic abscesses as well. In contrast to the literature, this case is not related to prosthetic devices; an untreated limb wound may have been the site of microbial entry. PMID- 11218633 TI - Trauma sites and clinical features associated with acute hyperextension spinal cord injury without bone damage--relationship between trauma site and severity. AB - To elucidate whether a relationship exists between the site of trauma and severity of acute hyperextension spinal cord injury without bone damage, we examined the clinical features of 25 male and 10 female patients aged 13 to 88 years. None of the patients had vertebral damage such as fracture and dislocation. The site of impact was classified as the buccal, forehead, or mandibular region. The neurological findings were assessed according to Frankel's classification at admission and at follow up after 3 months or more to assess outcome. Eleven patients suffered trauma in the buccal region, one patient in Frankel's grade B, three in grade C, and seven in grade D at admission. All 11 of these patients showed an improvement of one grade or more to an outcome of C in one patient, D in one, and E in nine. Trauma occurred at the forehead region in 18 patients, four in grade B, 10 in grade C, and four in grade D. Improvement was seen at follow up by one grade or more to C in one patient, D in 10, and E in seven. Trauma occurred at the mandibular region in six patients, four in grade B and two in grade C. Four of these patients showed improvement of one grade or more to grade B in one, grade C in four, and grade E in one. Overall, seven patients had poor outcomes, five of whom suffered trauma to the mandibular region, indicating that impact to the mandibular region tends to have an unfavorable clinical outcome. Our findings indicate that the site of trauma greatly influences the severity of hyperextension spinal cord injury. PMID- 11218634 TI - Relationship between stroke and asymptomatic minute hemorrhages in hypertensive patients. AB - Asymptomatic small hemorrhages were identified in hypertensive patients by T2* weighted gradient echo magnetic resonance (MR) imaging to investigate the relationship between hypertensive intracerebral hemorrhage and asymptomatic minute hemorrhages. Forty-eight patients with hypertensive intracerebral hemorrhage or cerebral infarction with hypertension (these diseases were defined as stroke) were treated in National Defense Medical College from April 1998 to February 2000. All patients had no past history of stroke or head injury, underwent MR imaging within 6 months of the stroke attack, were aged from 40 to 80 years, and had no diagnosis of aneurysm, angioma, or moyamoya disease. Patients were divided into the infarction group and hemorrhage group. All foci over 2 mm in size appearing as hypointense on T2*-weighted MR imaging and unrelated to stroke areas were defined as minute hemorrhages. There were no significant differences between the two groups with respect to sex, age, and history of diabetes mellitus. The incidence of minute hemorrhages in the hemorrhage group (21/26) was greater than in the infarction group (9/22, p < 0.01). The incidence of minute hemorrhages in the basal ganglia (18/26) was greater in the hemorrhage group than in the infarction group (4/22, p < 0.001). Symptomatic intracerebral hemorrhage may be preceded by asymptomatic minute hemorrhage. PMID- 11218635 TI - Organized chronic subdural hematoma requiring craniotomy--five case reports. AB - Two child and three elderly patients underwent craniotomy for organized and/or partially calcified chronic subdural hematomas (CSHs). The characteristic feature of magnetic resonance imaging was a heterogeneous web-like structure in the hematoma cavity. Both children had undergone one side subduroperitoneal shunt for bilateral CSHs when infants. As a result, the opposite hematoma cavities persisted and developed into calcified CSHs after a couple of years. All three elderly patients with senile brain atrophy showed various systemic complications such as cerebral infarction, diabetes mellitus, leg ulceration, cirrhosis, and bleeding tendency. Craniotomy for removal of the hematoma and calcification achieved good results in all patients. Subdural space created by shunt, craniotomy, or brain atrophy and persisting for a certain period, and additional various brain damage such as microcirculatory disorder, meningitis, encephalitis, or premature delivery may be important in generating calcified or organized CSH. PMID- 11218636 TI - Successful treatment of a ruptured enlarged infundibular widening of the posterior communicating artery--case report. AB - A 67-year-old female with a history of hypertension and cerebral infarction presented with subarachnoid hemorrhage (SAH) (Hunt and Kosnik grade 4). Brain computed tomography (CT) revealed a clot dominantly on the right (Fisher's classification Group 4). Cerebral angiography showed funnel-shaped widenings at the origins of the bilateral posterior communicating arteries. The maximum diameter of the widening was greater than 3 mm, so this widening was called an enlarged infundibular widening. Angiography showed a small bulge protruding posterolaterally from the wall of the right enlarged infundibular widening, and the right posterior communicating artery arose from the apex of the enlarged infundibular widening. Based on the findings of the brain CT and cerebral angiography, the diagnosis was SAH due to rupture of the right enlarged infundibular widening. Approximately 12 hours after the onset, the clot was evacuated through the right pterional approach. Bleeding from the small bulge of the right enlarged infundibular widening occurred intraoperatively, so a right angled ring clip was applied parallel to the right internal carotid artery to obliterate the rupture point. Postoperatively, she was discharged without neurological deficit, and follow-up CT showed no other new infarction. We recommend clipping rather than wrapping or coating for similar cases of ruptured enlarged infundibular widening. PMID- 11218637 TI - Kissing mirror image anterior communicating artery aneurysms--case report. AB - A 45-year-old male presented with an extremely rare case of symmetrical kissing aneurysms located at the both ends of the anterior communicating artery. Angiography and three-dimensional computed tomography (3D-CT) angiography clearly showed the relationship of the kissing aneurysms. The aneurysms were clipped through the right pterional approach. Temporary clipping of the anterior cerebral arteries for 5 minutes was required to gain enough operative space. The patient was discharged without neurological deficits. 3D-CT angiography, magnetic resonance angiography, or rotatory digital subtraction angiography may be useful for detecting kissing aneurysms, but the most important issue is awareness of this unusual condition. PMID- 11218638 TI - Serial neuroimaging of a growing thrombosed giant aneurysm of the distal anterior cerebral artery--case report. AB - An 81-year-old female presented with a giant aneurysm of the distal anterior cerebral artery (A3) which grew from a small saccular aneurysm to a huge aneurysm within 36 months before manifesting as a mass lesion. The thrombosed portion of the aneurysm showed growth, whereas the aneurysmal cavity did not change in size. Computed tomography and magnetic resonance imaging showed new bleeding in the thrombosed portion. Hemorrhage into the thrombus and/or aneurysmal wall might have caused the aneurysmal growth. She refused surgery and was discharged with no deficits. Distal anterior cerebral artery aneurysm which shows neuroimaging signs of growth requires regular follow up as such lesions may become giant before manifesting clinical symptoms. PMID- 11218639 TI - Moyamoya disease and coronary artery disease--case report. AB - A 26-year-old female with idiopathic moyamoya disease developed chest pain with concomitant ST depression on electrocardiography. Coronary angiography detected no stenotic lesions in the epicardial coronary arteries. The clinical diagnosis was vasospastic angina pectoris. She was medicated with calcium antagonists, which reduced the frequency of chest pain episodes. Angina pectoris is a rare occurrence in young patients with moyamoya disease. Coronary artery disease and moyamoya disease may have common etiological factors. PMID- 11218640 TI - Bone defect associated with middle meningeal arteriovenous fistula treated by embolization--case report. AB - A 57-year-old male presented with a frontal bone defect associated with a middle meningeal arteriovenous fistula (AVF) manifesting as headache. The patient had a history of head injury 19 years previously. Skull radiography and computed tomography demonstrated a left frontal bone defect. Left external carotid angiography demonstrated a middle meningeal AVF at the frontal region, at the same location as the bone defect. The AVF was fed by the bilateral middle meningeal and left deep temporal arteries, and drained by the superior sagittal and ipsilateral cavernous sinuses. The minor feeding artery, the left deep temporal artery, was embolized with polyvinyl alcohol particles, then 0.4 ml of a 1:3 mixture of n-butyl cyanoacrylate and lipiodol was injected from the left middle meningeal artery. Follow-up angiography 3 months after the embolization revealed complete obliteration of the fistula. The bone defect may have been caused by erosion of the frontal bone by the pulsating effect of the feeding and draining vessels of the fistula, or by inadequate nutrition to the bone tissue because of the arteriovenous shunt. PMID- 11218641 TI - Neurosarcoidosis without systemic sarcoidosis--case report. AB - A 20-year-old male presented with symptoms of isolated neurosarcoidosis including epilepsy. Magnetic resonance imaging disclosed multiple enhanced right temporal and frontal lesions. Cerebrospinal fluid examination identified mild lymphocytic pleocytosis, and histological examination of a stereotactic brain biopsy specimen demonstrated noncaseating granulomas, so fungal or other inflammatory or granulomatous diseases were excluded. The diagnosis was cerebral sarcoidosis, despite the absence of systemic manifestations. Corticosteroid therapy improved his neurological state and radiological findings. Neurosarcoidosis is a well recognized occurrence in systemic sarcoidosis, but diagnosis may be difficult in the absence of extracerebral manifestations. PMID- 11218642 TI - High incidence of arterial dissection associated with left vertebral artery of aortic origin. AB - The incidences of arterial dissection of the vertebral artery (VA) of aortic origin and VA of subclavian artery origin were determined. The origins of the left and right VAs were confirmed by angiography in 860 and 717 patients, respectively. Left VA of aortic origin was found in 21 patients (6 females and 15 males) but no right VA of aortic origin was found. Left VA of left subclavian artery origin was found in 837 patients and right VA of right subclavian artery origin in 717 patients. Arterial dissection of the VA occurred in 17 patients (6 females and 11 males), four patients with left VA of aortic origin, seven with left VA of left subclavian artery origin, four with right VA of right subclavian artery origin, and two with bilateral VAs of subclavian artery origin. Left VA of aortic origin (4 of 21 patients) was associated with a significantly higher incidence of VA dissection than left VA of left subclavian artery origin and right VA of right subclavian artery origin (p < 0.001). Left VA of aortic origin is associated with a predilection for VA dissection in comparison to VA of subclavian artery origin. PMID- 11218643 TI - Investigation of connexin gene expression patterns by in situ hybridization techniques. PMID- 11218645 TI - Expression and imaging of connexin-GFP chimeras in live mammalian cells. PMID- 11218644 TI - Biochemical analysis of connexon assembly. PMID- 11218646 TI - Analysis of connexin expression in brain slices by single-cell reverse transcriptase polymerase chain reaction. PMID- 11218647 TI - Use of retroviruses to express connexins. PMID- 11218648 TI - Spatiotemporal depletion of connexins using antisense oligonucleotides. PMID- 11218649 TI - Transfection and expression of exogenous connexins in mammalian cells. PMID- 11218650 TI - Assaying the molecular permeability of connexin channels. PMID- 11218651 TI - Applying the Xenopus oocyte expression system to the analysis of gap junction proteins. PMID- 11218652 TI - Mutagenesis to study channel structure. PMID- 11218653 TI - Dual patch clamp. PMID- 11218654 TI - Determining ionic permeabilities of gap junction channels. PMID- 11218655 TI - Fluorescence recovery after photobleaching. PMID- 11218656 TI - Capture of transjunctional metabolites. PMID- 11218657 TI - Sodium dodecyl sulfate-freeze-fracture immunolabeling of gap junctions. PMID- 11218658 TI - The study of connexin hemichannels (connexons) in Xenopus oocytes. PMID- 11218659 TI - Exploring hemichannel permeability in vitro. PMID- 11218660 TI - Inducing de novo formation of gap junction channels. PMID- 11218661 TI - Recording and analysis of putative direct electrical interactions in the mammalian brain. PMID- 11218662 TI - Intercellular calcium signaling and flash photolysis of caged compounds. A sensitive method to evaluate gap junctional coupling. PMID- 11218663 TI - Biochemical analysis of connexin phosphorylation. PMID- 11218664 TI - How to close a gap junction channel. Efficacies and potencies of uncoupling agents. PMID- 11218665 TI - Purification of gap junctions. PMID- 11218666 TI - Culturing of mammalian cells expressing recombinant connexins and two-dimensional crystallization of the isolated gap junctions. PMID- 11218667 TI - Connexins/connexons. Cell-free expression. PMID- 11218668 TI - HBV-DNA detection in hepatitis B infection. PMID- 11218669 TI - Histopathology of skin lesions in chronic arsenic toxicity--grading of changes and study of proliferative markers. AB - Chronic arsenic toxicity (CAT) manifests predominantly as cutaneous lesions in the form of melanosis, keratosis and neoplastic changes. We have studied skin biopsies from 42 patients of CAT. Histological study of H/E stained sections showed--hyperkeratosis in 13, parakeratosis in 13, acanthosis in 12, papillomatosis in 24, elongation of reteridges in 21, increased basal pigmentation in 27 and dysplastic changes in 8 cases. Squamous cell carcinoma was present in 2, basisquamous in 1 and basal cell carcinoma in 1 case. Changes of skin lesions after drug DMSA and DMPS therapy compared to placebo were studied. The result was inconclusive. Proliferative activity of skin lesions in CAT were studied by AgNOR stain to assess the biological behaviour of the lesions. AgNOR score showed--normal control 1.08, benign changes (e.g. Hyperkeratosis, parakeratosis, acanthosis, papillomatosis etc.) without dysplasia--1.35, mild to moderate dysplasia--1.735, severe dysplasia--3.0 and carcinoma--3.56. Thus, AgNOR score gives some idea on the biological behaviour of CAT lesions. It is suggested that AgNOR staining should be done regularly along with H&E staining for proper assessment of the cases. PMID- 11218670 TI - DNA aneuploidy in invasive carcinoma of the uterine cervix. AB - Forty cases of squamous cell carcinoma and twenty cases of adenocarcinoma of the cervix were subjected to DNA ploidy analysis to find out the frequency of aneuploid DNA pattern in different types of invasive carcinoma of the uterine cervix and their possible correlation with the clinical stage and age of the patients. From the DNA analysis an increasing trend of DNA aneuploidy was observed from well differentiated (63.6%) to moderately differentiated (70.8%) to poorly differentiated squamous cell carcinoma (83.3%). However, 85% adenocarcinomas of endocervix showed aneuploid DNA pattern. It indicates that aneuploidy increases with tumour dedifferentiation and further confirms the importance of DNA ploidy as a high risk indicator. PMID- 11218671 TI - Correlations between apoptotic and proliferative indices in cervical intraepithelial neoplasia and carcinoma. AB - Aims of the present paper was to study cell death by apoptosis and cell proliferation in normal cervical biopsies, cervical intraepithelial neoplasms (CIN) and squamous cell carcinomas of cervix (CaCx). There were each seven cases of normal cervical biopsy, CIN1 and CIN2 along with 10 cases of CIN3 and 14 cases of CaCx. Percentage of apoptotic cells and bodies (i.e. apoptotic index, AI) and mitoses (i.e. mitotic index, MI) and turnover index (TI - AI + MI) were counted in formalin fixed, paraffin embedded, haematoxylin and eosin stained slides. AgNOR stain was done and mean AgNOR dots per cell was also estimated. AI, MI and TI were correlated with histology grade of CIN and invasive carcinoma cervix. Mean AI, MI, TI and AgNOR count increased from lower to higher grades of CIN. AI, MI & TI raised significantly from CIN3 to carcinomas; AI, TI & AgNOR count raised significantly from CIN1 to combined CIM2 & 3; TI & AgNOR count were high in CIN1 to CIN2; AI & TI were significantly raised in normal to CIN1. In conclusion, TI is probably more important for cell kinetic analysis of CIN and carcinoma of cervix because it reflects the frequency of two important events i.e. mitosis and cell death. Sudden increase of AI, MI, TI count from CIN3 to CaCx may indicate the possibility of genetic alteration of cells of CIN3 which induces a frank malignant transformation from CIN3 to CaCx. PMID- 11218672 TI - Isolated right ventricular infarction. AB - Rare occurrence of isolated right ventricular infarction is reported in four patients, three of whom were elderly. The causes of infarction were due to pulmonary thromboembolism and dissection of non-dominant right coronary artery. None of the hearts had right ventricular hypertrophy and significant coronary atherosclerosis. PMID- 11218673 TI - In vitro susceptibility testing of nonsporing anaerobes to ten antimicrobial agents. AB - Antibiotic susceptibility was performed on sixty clinical isolates of nonsporing anaerobes against ten antimicrobial agents. The test was performed on Muller Hinton Agar and Wilkins Chalgren blood agar by preparing suspension of freshly isolated colonies in BHI broth. Apart from Metronidazole and Chloramphenicol newer antibiotics like Minocycline, Secnidazole, Tinidazole, Clarithromycin, Roxithromycin were also tried. Antimicrobial agents like Metronidazole, Secnidazole, Tinidazole and Minocycline were 100% sensitive, followed by Chloramphenicol, Clarithromycin and Roxithromycin. These newer agents can be good alternatives for the treatment of non sporing anaerobes. PMID- 11218674 TI - Expression of CXCR4 in the brain of feline immunodeficiency virus infected cat. AB - Advances in understanding the mechanisms of human immunodeficiency virus (HIV)-1 entry have revealed that the cell surface CD4 expression alone is insufficient and needs an additional molecule on its surface for the viral entry. These are G protein coupled seven transmembrane (7-TM) family molecules (chemokine receptor) and amongst them one is CXCR4. Feline homologue of CXCR4 acting as a co-receptor for feline immunodeficiency virus (FIV) entry is already reported for the Crandle feline kidney cells strain (CrFK) of FIV. An experiment was carried out to search the expression of CXCR4 retrospectively in FIV (CrFK) infected cat brain tissues using immunohistochemically in the formalin fixed paraffin sections against 12G5, a mouse monoclonal antibody to CXCR4. We observed the expression of this receptor in feline neurons, astrocytes and in some vascular endothelial cells. The study of expression of CXCR4 in the brain, which is one of the many chemokine receptors in the central nervous system, may provide further insight into the interactions between brain cells, pathogens, and the immune system, and help understand the pathogenesis of HIV dementia. PMID- 11218675 TI - Identification of Pneumocystis carinii in induced sputum of AIDS patients in Chennai (Madras). AB - Induced sputum samples were collected from 32 AIDS patients with respiratory ailments. Pneumcystis carinii was demonstrated in 9 out of 32 AIDS cases by Indirect Immunofluorescence technique (HF). Four cases were positive by all the three techniques namely Giemsa staining, Toluidine blue staining and IIF, three were positive by both toluidine blue and IIF, and two were positive only by IIF. Among other microbial pathogens, acid fast bacilli was demonstrated in all the P carinii positive cases and Candida albicans in 53% AIDS cases from the induced sputum sample. PMID- 11218676 TI - Clinical spectrum of Glanzmann's thrombasthenia. AB - Glanzmann's thrombasthenia is a well defined inherited disorder of platelet function characterized by qualitative and qualitative defect in cytoadhesive membrane protein, glycoprotein IIb-IIIa (the platelet fibrinogen receptor). From January 1990 to October, 1999, five patients who presented with mucocutaneous bleeding were detected to have Glanzmann's thrombasthenia. Clinical and laboratory spectrum of this rare disorder was studied which revealed heterogeneity of disease with respect to nature and severity of bleeding unpredictable by laboratory findings. PMID- 11218677 TI - Cytohistological study of urinary bladder neoplasms. AB - Eighty patients presenting with painless hematuria and 24 patients of transitional cell carcinoma bladder coming for follow up were included in this study to assess the role of exfoliative (voided urine) and lavage (saline lavage) cytology in initial diagnosis and follow up of the patient with carcinoma bladder. Freshly voided urine samples and saline lavage bladder washing samples were collected. A thorough cystoscopic examination was done and biopsy was taken from any apparent growth. Cytological smears were stained with hematoxylene and eosin and PAP's stain, histology sections were stained with hematoxylene and eosin. A statistically significant correlation (p < 0.001) was observed between the increasing grade of malignancy and cytopositivity. A good association was observed between histology and two methods of cytology (p < 0.01). The sensitivity, specificity and overall diagnostic accuracy of lavage cytology was more as compared to exfoliative cytology (71.05%, 56.0%, 78.85% Vs 47.37%, 41.18% and 61.54%). Cystopositivity was more with single large sessile tumour as compared to multiple small pedunculated tumours. Cytohistological discrepancy was observed in patients of transitional cell carcinoma with recurrence. It is concluded that cytology may act as a good adjuvant to histology in picking up early flat lesions and/or follow up of patients with transitional cell carcinoma. PMID- 11218678 TI - Fatal complications of systemic lupus erythematosus--an autopsy study from north India. AB - Systemic lupus erythematosus (SLE) is a multisystem, autoimmune disease with varied clinical manifestations and outcome. It may prove fatal due to disease activity or intercurrent infections. In recent years, earlier diagnosis and better treatment modalities have resulted in a change in the pattern of organ involvement and mode of death in the west. This aspect of the disease is unknown in India. Hence, in this autopsy series of SLE, the organ involvement and cause of death have been studied. Twenty five cases of clinically diagnosed SLE have been analysed retrospectively. Renal involvement was invariably present (96%) with class IV being the commonest lesion in 60% cases. Disease activity was noted in 60% cases. Pleuro pulmonary lesions were seen in 92% cases with infection being the commonest. Pulmonary infections included bacterial pneumonias (13), disseminated tuberculosis (3), pulmonary mucormycosis (1) and aspergillosis (1). Massive pulmonary haemorrhage in 5 cases and acute lupus pneumonitis in one, contributed to the demise of the patient. Vasculitis was evident in single organ in 9 cases, in two or more organs in 3 cases with systemic vasculitis significantly attributing to morbidity in 1 case. Active disease was the cause of death in 60% cases and infection in 40%. PMID- 11218679 TI - Prothrombotic factors in nephrotic syndrome. AB - Nephrotic syndrome is a hypercoagulable state with variable prevalence of clinical thrombosis. The role of platelet aggregation, fibrinogen and antithrombin III and protein S levels in the pathogenesis of hypercoagulable state in these patients is controversial. Since no study on Indians is available, the clinical and laboratory profile of 22 patients of nephrotic syndrome (age 18 35 years with an MF ratio of 4:3), have been studied. The coagulation profile revealed a prolonged APTT in 12 patients (54.5%), and a prolonged TT in four (18.1%). In the rest APTT and TT were normal. PT was raised in two patients. Fibrinogen, an acute phase reactant was raised in five patients (22.7%). Antithrombin III levels were reduced in 19 patients (86.4%), normal in one and raised in two patients. Free Protein S levels were high in 12(54.5%), normal in seven and decreased in three patients. Platelet aggregation with adrenaline and adenosine diphosphate was raised in 6 patients. Ultrasonographically detected deep vein thrombosis was seen in one patient only (4.5%) who had ATIII levels of 48%. This low incidence can be explained by elevated protein S levels which was found to be raised in 12(54.5%) cases, protein S being an anticoagulant factor. This low level of clinical thrombosis in Indian patients of nephrotic syndrome may be an ethnic variable factor. It is thus concluded that although patients with nephrotic syndrome have a hypercoagulable state, clinical thrombosis is rarely seen in Indian patients with nephrotic syndrome. PMID- 11218680 TI - Serum lactate dehydrogenase in diagnosis of megaloblastic anaemia. AB - The present study was carried out in 75 patients of macrocytic anaemia categorised on bone marrow examination (into megaloblastic and non-megaloblastic anaemia) to evaluate the efficacy of total serum LDH levels and LDH isoenzyme pattern in the diagnosis of megaloblastic anaemia. 25 healthy adults were taken as controls. From this study it can be concluded that total serum LDH levels more than 3000 IU/L are diagnostic of megaloblastic anaemia. Reversed LDH isoenzyme pattern (LDH1 > LDH2) by chloroform inhibition test is an adjuvant in the diagnosis where total serum LDH levels are between 451-3000 IU/L and it will also differentiate megaloblastic anaemia from haemolytic anaemia. PMID- 11218681 TI - Evaluation of leukergy test as an indicator of infection in hip joint in children. AB - This new blood test (leukergy) for infection is based on the fact that white cells agglomerate in peripheral blood of patients with inflammatory diseases. We evaluated leukergy in 25 children with proven septic arthritis of hip. It was found to be the efficient and earliest indicator of septic arthritis than the erythrocyte sedimentation rate (ESR), total leucocyte count (TLC), polymorphs and C-reactive protein (CRP). It also correlated well with the clinical severity of infection and the prognosis of disease. Thus leukergy is a simple, rapid and inexpensive slide test which was found as the best indicator profile for the presence of septic arthritis. PMID- 11218682 TI - Leptospirosis in the causation of hepato-renal syndrome in and around Pune. AB - Fifty cases of hepato-renal dysfunction of unknown etiology were studied over a two-year period. Urine samples were examined microscopically and cultured for Leptospira. Serum samples were examined for antibodies against Leptospira by the Macroscopic slide agglutination test (MSAT). Seventeen out of fifty patients (34%) showed evidence of Leptospiral infection by at least two diagnostic techniques used. 15/17 i.e. 88.2% were positive by dark ground microscopy, 7/17 were diagnosed by culture technique and 16/17 i.e. 94% were confirmed by serology. There was a good correlation between Microscopic agglutination test (MAT) and MSAT. Thus Leptospires seem to play a major role in the causation of hepato-renal dysfunction in and around Pune, Maharashtra. PMID- 11218683 TI - Rapid identification of fluconazole resistance using Chromagar Candida. AB - Although extremely rare 10 years ago, antifungal drug resistance is becoming a major problem in certain populations, especially in those infected with HIV. This study was undertaken to study the resistance of Candida species isolated in our hospital to Fluconazole using Chrom agar Candida. The Candida strains which were routinely isolated from clinical specimens like blood, urine, sputum, pus, fluid and homograft isolates were included in the study. 142 Candida isolates were tested by using Chrom agar Candida incorporated with fluconazole. 16 strains were found to be resistant to Fluconazole and 126 strains sensitive to Fluconazole. Nine were C tropicalis, 3 C krusei, 2 C guillermondii, 1 Geotrichum candidum and one was an unidentified strain of Candida. The MIC of the 16 strains were done using RPMI 1640 medium by macro broth dilution method. MIC of 9 strains was 64 & > 64 micrograms/ml of 6 strains 32 micrograms/ml and 1 strain 16 micrograms/ml. PMID- 11218684 TI - Congenital infantile fibrosarcoma of the upper extremity. AB - Congenital-infantile fibrosarcoma is an unusual childhood tumor that occurs mainly in children under 5 years of age. More than 300 cases have been reported in the literature so far, very few of them at birth. A distinction must be made between it and its adult counterpart because of differences in their clinical behaviour. We report here a case of congenital fibrosarcoma in a 4-day-old female infant. PMID- 11218685 TI - Intrapericardial teratoma--a report of two cases. AB - Two rare cases of intra-pericardial teratoma in infants are reported. The presenting symptoms were either due to pericardial effusion and cardiac tamponade or due to compression of the tracheo-bronchial tree. The tumors were well encapsulated and were attached to the ascending aorta. Histologically, they were composed of derivatives of the three germ cell layers. PMID- 11218686 TI - Giant cell tumour of soft tissue--a case report. AB - Giant cell tumor is seen in late adolescence or in the third or fourth decade of life. It arises from epiphysis of long bones, the commonest site being the distal end of the femur and the proximal end of tibia. This paper presents a case report of giant cell tumor of soft tissue. PMID- 11218687 TI - Hairy polyp of nasopharynx--a case report. AB - A specific subtype of teratoid tumour occurring in nasopharynx and oropharynx has been mentioned as 'hairy polyp'. This is a rare lesion and is to be differentiated from true teratomas. A case of hairy polyp of nasopharynx in a 12 year old girl is reported. PMID- 11218688 TI - Pleomorphic xanthoastrocytoma--a clinicopathological study. AB - Six cases of Pleomorphic Xanthoastrocytoma of central nervous system are presented. One case presented with recurrent refractory seizures and others as intracranial space occupying lesions. They were located in temporal/parietal lobes, were partly cystic and partly solid on CT scan, enhancing with contrast. Histopathology was characterized by pleomorphic giant cells and cells with vacuolated cytoplasm. Glial fibrillary acidic protein was strongly positive in all the cases. PMID- 11218689 TI - Breast filariasis--a case report. AB - An unusual presentation of filariasis as a breast lump simulating breast carcinoma, in a 50 year old woman residing in Pokhara, Nepal. The case was reported on Fine Needle Aspiration Cytology and also evaluated by histopathology. Morphology of the nematode is that of Brugia species which is unusual in Nepal. PMID- 11218690 TI - Metastatic carcinoma in hepatic hemangioma. AB - Metastasis into the hepatic hemangioma is a rare occurrence. We report a unique case of metastasis of intestinal carcinoma into hepatic hemangioma in a case of 65 year old male who presented with anorexia, weakness and headache. The postmortem examination revealed adenocarcinoma in the ileocaecal region. The liver showed a subcapsular hemangioma of 1.5 cms. diameter which on microscopic examination revealed metastasis of adenocarcinoma. The is the first documentation of metastasis in hepatic hemangioma. Such cases may pose problems of diagnostic difficulties and thus may result in mismanagement. PMID- 11218692 TI - Chediak-Higashi syndrome--a case report. AB - Chediak Higashi anomaly is a very rare disorder in which patients suffer frequent and severe pyogenic infections that are secondary to abnormal functions of polymorphonuclear leukocytes, associated with albinism and bleeding tendency. Blume RS and Wolff SM (1972) reported that only 59 cases were diagnosed after the first description of Chediak-Higashi Syndrome in 1943 by Cesar AB (cited by Wintrobe MM Clinical Haematology). As per recent literature available (Internet) last case was reported on 16th July, 1997. PMID- 11218691 TI - MALT lymphoma of the intestine. A clinicopathological study over a period of 13 years. AB - Clinicopathological features of 14 patients with histologically confirmed primary intestinal Non-Hodgkin lymphoma were analysed. Patients were mostly young males with median age of 27.2 years. Main presenting features was intestinal obstruction. Diffuse large cell lymphoma was the commonest histological type. All cases were found to be B cell type in immunohistochemistry. PMID- 11218693 TI - Hepatitis C virus: biology and diagnosis. PMID- 11218694 TI - Unverified rumours of viral haemorrhagic fever, Democratic Republic of the Congo. PMID- 11218696 TI - Dracunculiasis, Yemen. PMID- 11218695 TI - Onchocerciasis (river blindness). PMID- 11218697 TI - [A one-month combined use of selective adrenergic beta 1- and alpha 1-agonists for postprandial hypotension in patients with autonomic failure]. AB - In 1993, we reported the pathophysiology of postprandial hypotension (PPH) in patients with sympathetic dysfunction: a fall of BP resulted from both excess systemic vasodilation and lack of compensatory increase of cardiac output and vascular resistance in the leg arteries. In that article, we showed the beneficial results of combined oral administration of denopamine (a selective beta 1-agonist) and midodrine HCI (a selective alpha 1-agonist) on this condition. The present study was undertaken to further evaluate the efficacy and safety of this agonist combination in autonomic failure (AF) patients with PPH. This was a one-month trial. A total of 13 chronic AF patients received orally 30 mg of denopamine and 12 mg of midodrine three times a day, 30 minutes before each meal. We measured brachial BP every 10 min in the daytime and every 15 min in the nighttime, using a 24-h indirect BP recorder. The combined use of these agonists produced a significant improvement in PPH and maintained a near-normal BP level. In conclusion, the combined administration of denopamine and midodrine three times a day is a well-tolerated and efficacious treatment for PPH. PMID- 11218698 TI - [Serological diagnostic trial of the causative virus of Bell's palsy by anti herpes virus antibodies in the paired sera]. AB - Substantial evidence obtained through polymerase chain reaction techniques strongly supports that reactivation of latently infected herpes simplex virus (HSV) in geniculate ganglia is the main cause of Bell's palsy. However, serum antibody titers to HSV rarely increase in patients with this disease. This discrepancy may result from the difficulty in detecting a small increase in antibody titers by conventional serological analysis. To detect such a small increase in antibody titer, we defined the significant increase in IgG antibody titers more precisely, and examined the association of HSV or varicella-zoster virus (VZV) with Bell's palsy. From 40 patients with Bell's palsy, paired sera were obtained within the 4th disease day and 2 weeks later. IgG antibodies to HSV, VZV, cytomegalovirus (CMV), or measles virus (MsV) were measured with solid phase enzyme immunoassay (EIA). IgM antibodies were measured with captured EIA. Each antibody titer was expressed as an EIA-value, which was quantitatively measured by using a calibration curve prepared from the samples containing known titers to the virus in proportion to the logarithm of its titer. An EIA-value ratio (EVR) between paired sera and a corrected EVR was calculated according to the formulae: EVR = [EIA-value in the second serum]/[EIA-value in the first serum]; corrected EVR = [EVR to HSV, VZV or CMV]/[EVR to MsV]. The association with a virus was determined to be positive when the corrected EVR of the virus was beyond the normal range (the logarithmical mean +/- 3 SD of corrected EVRs among 24 healthy controls) while the corrected EVR of the other viruses were within it. Using the corrected EVR, 6 patients were positive: 4 for HSV, 2 for VZV. On the other hand, the conventional serological analysis, which confirms positivity by a 4-fold increase in IgG antibody titer or a demonstration of IgM antibody, disclosed only 2 positive patients (1 for HSV, 1 for VZV). EIA is a very sensitive method of detecting antibodies. Corrected EVRs can exclude a decrease in antibody titers induced by corticosteroids, which are generally used for therapy of Bell's palsy. Moreover, the normal range of corrected EVRs can be defined more precisely than in conventional serological analyses. Our results indicate that some sensitive analysis, such as the corrected EVR method, may make it possible to serologically detect the causative virus of Bell's palsy. PMID- 11218699 TI - [A case of myasthenia gravis following sarcoidosis and Hashimoto's thyroiditis]. AB - Here, we report on an elderly woman with sarcoidosis and Hashimoto's disease who later developed myasthenia gravis. She was 68-year-old with a long history of Hashimoto's disease who had a clinical diagnosis of sarcoidosis with uveritis at the age of 66 years. On laboratory examination, angiotensin-converting enzyme, lysozyme and gamma-globulin were elevated and there was bilateral hilar lymphoadenopathy. She was admitted to our hospital because of left blepharoptosis and mild fatigability in the proximal muscles at the age of 68 years. Myasthenia gravis, type IIa, was confirmed by elevated titer of anti-acetylcholine receptor antibody in serum (0.8 nmol/l, normal < 0.6), positive edrophonium test and decremental EMG response. Oral prednisolone therapy was effective. Her muscle biopsy revealed HLA ABC-positive fibers in all fascicles, and HLA-DR positive fibers in the perifascicular areas. Myasthenia gravis complicated by sarcoidosis and Hashimoto's thyroiditis is extremely rare, suggesting that the common underlying immunological abnormalities for the three disorders such as a certain defective cellular immunity are responsible for the pathomechanism to induce the patient condition. PMID- 11218700 TI - [An autopsied case of progressive spinal muscular atrophy showing tremor and choreiform movement]. AB - A 42-year-old man without family history of neurologic disease developed muscle weakness, and wasting associated with tremor and choreiform movement. He died at age 75 with 33 years of total duration of illness. Autopsy revealed neuronal loss and gliosis in the anterior horns of the spinal cord, hypoglossal nuclei, caudate nuclei, putamen, globus pallidus, and substantia nigra. Bunina bodies or Lewy bodies were not seen. Several similar cases with motor neuron disease, dementia and parkinsonism have been reported in the literature. However, this pattern of chronic spinal neostriato-pallido-nigral degeneration has not been reported. PMID- 11218701 TI - [A case of left third nerve palsy and contralateral vertical gaze palsy with medial midbrain infarction]. AB - An 81-year-old man developed oculomotor nerve palsy of the left eye and vertical gaze palsy of the right eye due to left medial midbrain infarction. His left eyelid was ptotic and the pupil was dilated. His right eye showed normal horizontal movement and Bell's phenomenon was preserved although the oculocephalic reflex was incomplete. There were no other abnormal neurological findings. The brain MRI revealed a high-intensity lesion in left medial midbrain on T2 weighted image. This lesion involved the oculomotor nerve nucleus, the interstitial nucleus of Cajal, and the rostral intersititial nucleus of the medial longitudinal fasciculus (riMLF). We thought that upward gaze palsy of the right eye was resulted from the infarction of the left riMLF or disruption of the axonal collateral of upward gaze fibers in the left oculomotor nucleus. Downward gaze palsy was resulted from the damage of the downward gaze fibers before their decussation, or the damage of the left interstitial nucleus of Cajal. This case provides evidence that unilateral lesion of the midbrain could cause contralateral vertical gaze palsy. PMID- 11218702 TI - [A case of Ondine curse associated with a medullary tumor]. AB - A 49-year-old woman with 6 months history of body weight loss, muscle weakness, and dysarthria, was found with respiratory arrest and resuscitated in the morning of January 1999. An MRI brain scan revealed diffuse swelling and T2/FLAIR high signal intensity with mild Gadolinium enhancement in the lower pons and medulla oblongata. Although the histological diagnosis could not be obtained, glioma (astrocytoma) was suspected. In the morning of July 3rd she presented sweating and cyanosis. Her arterial oxygen saturation was 18%. When we asked her to breathe more, she kept breathing and oxygen saturation was normalized. However, she could not breathe at all when she fell asleep without stimulation. She was kept under respiratory support for 2 months. Her symptoms improved with fluctuating course after 70 Gy of radiation therapy. Ondine curse is one type of sleep apnea syndrome, defined as the selective disturbance of autonomous breathing. Surgical operation and stroke are the reported causes of this syndrome. Brainstem tumor is relatively common cause for children's Ondine curse. On the other hand, it rarely causes adult's Ondine curse as a main symptom. PMID- 11218703 TI - [A case of chorea-acanthocytosis with dilated cardiomyopathy and myopathy]. AB - We report a patient of chorea-acanthocytosis (CA), presenting with dilated cardiomyopathy and myopathy. The patient, 40-year-old male, was seen in our clinic because of progressive gait disturbance. Neurologically, he had chorea, tic, dystonia, diminished tendon reflexes and mild muscular atrophy and weakness. Serum creatine kinase level was elevated to 5.514 IU/l, MRI study showed atrophy of the putamen and caudate nucleus. Peripheral nerve involvement was confirmed pathologically and electrophysiologically. Acanthocytosis was found after repeated blood examinations. Furthermore, he had dilated cardiomyopathy on echocardiogram and cardiac muscle biopsy, and his muscle biopsy taken from gastrocnemius indicated myopathic changes with fiber necrosis. From these clinical and laboratory data, he was suspected to have McLeod syndrome (McS). However, he had normal expression of Kell antigens, and direct sequence of XK gene from genomic DNA sample showed no mutations. Accordingly, he was diagnosed as having CA. As CA shares the similar clinical and laboratory features with McS except Kell antigens, the evaluation of Kell blood system is crucial for differential diagnosis. As seen in our patient, blood sampling should be repeated for identification of acanthocytosis, because the finding is not always clearly present. PMID- 11218704 TI - [Acquired immunodeficiency syndrome-associated progressive multifocal leukoencephalopathy treated with highly active anti-retroviral therapy]. AB - We reported a patient with acquired immunodeficiency syndrome (AIDS)-associated progressive multifocal leukoencephalopathy (AIDS-PML), whose condition improved after highly active anti-retroviral therapy (HAART). A 70-year-old man was admitted to our hospital because of worsening left hemiplegia and disturbance of consciousness. During the past 30 years, he frequently traveled to the United States and southeast Asia. On neurological examination, he was somnolent and left hemiplegia with severe rigospasticity was present. The deep tendon reflexes showed hyper-reflexes with extensor plantar responses. Laboratory studies showed pancytopenia and positive HIV-1 antibodies. The CD4 cell count was 38/mm3 and his HIV viral RNA load in the blood was 9,500 copies/ml. T2-weighted magnetic resonance imaging (MRI) of the brain revealed asymmetrical high intensity white matter lesions in the right fronto-parietal, and left frontal regions and in the cerebellar hemisphere. The cerebrospinal fluid (CSF) protein elevated to 91 mg/dl with a normal cell count. The diagnosis of PML was confirmed by the detection of JC virus DNA in the CSF using a nested polymerase chain reaction assay. Three weeks after starting HAART with zidovudine, lamivudine, and indinavir, he was able to respond to simple commands. Two months later, the HIV viral RNA load decreased to less than 400 copies/mm3, and no JC virus DNA was detected in the CSF, with an increase of the CD4 cell count to 285/mm3 in the blood. A follow-up MRI of the brain showed a reduction in the cerebellar and cerebral white matter lesions. The recovering immune function by decreasing of the HIV load after HAART might suppress JC virus replication. It was suggested that HAART would become a beneficial treatment for patients with AIDS-PML. PMID- 11218705 TI - [A novel adult case of acute necrotizing encephalopathy of childhood with bilateral symmetric thalamic lesions]. AB - This report describes a 46-year-old Japanese woman with bilateral symmetric thalamic necrosis. The unusual radiologic findings are discussed in relation with acute necrotizing encephalopathy (ANE) of childhood, a rare disease proposed by Mizuguchi et al. ANE affects young children and the incidence is highest between 6 and 18 months of ages. There is only one report of an adult case. The acute stage pathology in ANE can be summarized as acute edema and necrosis involving both gray and white matter by local breakdown of the blood-brain barrier. The radiologic findings in our case were similar to those in ANE of childhood. Though the pathogenesis between our adult case and ANE of childhood might be different, severe hypoalbuminea in our case could cause the alteration of permeability of the thalamic vessels, which might accelerate breakdown of the blood-brain barrier in the thalamus. PMID- 11218706 TI - [Midbrain infarction presenting isolated inferior rectus nuclear palsy]. AB - We presented a patient of isolated inferior rectus muscle palsy from midbrain lacunar infarction involving the oculomotor nucleus. The patient noticed sudden onset diplopia gazing to the right side, especially to the right-lower direction. He did not have any other symptom, and neurological examination revealed no other findings. Brain MRI documented the focal hyperintense lesion on T2-weighted images in the right-median midbrain ventral to the aqueduct at the level of the superior colliculus. This lesion involved the right oculomotor nucleus, especially the dorso-lateral subnucleus extend to the inferior rectus muscle. The oculomotor nuclear complex consists of one unpaired subnucleus and four paired subnuclei. Among them, the inferior rectus subnucleus lies dorso-laterally. So nucleus lesion may cause isolated weakness of one of muscles innervated by the oculomotor nerve. Among them the isolated inferior rectus muscle palsy can occur relatively. PMID- 11218707 TI - [A case of acute motor sensory axonal polyneuropathy after Haemophilus influenzae infection]. AB - A 47-year-old woman developed consciousness disturbance, and experienced hallucinations while traveling abroad, and then went into critical condition. She was placed in the critical care unit, and had flaccid tetraparesis requiring mechanical ventilation. Haemophilus influenzae was cultured from the sputum. The level of protein of the cerebrospinal fluid was elevated to 114 mg/dl, nerve conduction study showed findings of pure axonal damage, and the sural nerve biopsy revealed severe axonal degeneration. She improved gradually by plasma exchange. The diagnosis of acute motor sensory axonal polyneuropathy (AMSAN) based on autoimmune mechanism was made. We speculate that H. influenzae infection may have elicited AMSAN in this case. PMID- 11218708 TI - [Progressive paralysis of divergence in an adult with midbrain angioma]. AB - A 37-year-old woman was admitted to the hospital with the complaint of progressive horizontal diplopia of six years' duration when viewing distant objects. On admission she had a slight left convergent strabismus. Homonymous diplopia was present beyond 50 cm and increased on distance fixation. Both eyes were fully mobile in the horizontal plane with a mild decrease in the velocity of horizontal eye movement to the left, and slight impairment of upward eye movement. The left eye did not fully adduct during convergence. The right pupil was slightly larger than the left. Prism cover test showed 6 delta esophoria at 30 cm and 14 delta esophoria at 5 m. The Hess chart showed a convergent deviation. MRI revealed a small right-side paramedian lesion of the midbrain tegmentum lying ventral to the aqueduct of Sylvius, at the level between the superior colliculi and the intercollicular area. A venous angioma with arteriovenous shunts in the right midbrain was diagnosed by angiography. We suggest that lesions that damage the divergence neurons in the tegmentum of the midbrain and also interrupt the supranuclear fibers having an inhibitory effect on the convergence neurons may produce homonymous diplopia on distant fixation combined with the esotropia. PMID- 11218709 TI - [Sudden bilateral hearing loss with vertigo due to vertebral artery occlusion]. AB - We report a case of sudden bilateral hearing loss associated with an occlusion of the right vertebral artery. A 66-year-old man was admitted to hospital suffering from sudden onset vertigo, deafness, and vomiting. He could not walk due to truncal ataxia. There was positional nystagmus to the right; spontaneous and gaze evoked nystagmus were absent. He had no facial nerve palsy, dysarthria, pyramidal tract signs, limb ataxia, and sensory impairment. Pure tone audiometry demonstrated a profound sensorineural deafness of both ears. A tentative diagnosis of sudden deafness was made. He was treated with intravenous infusion of corticosteroid; hearing loss of the left ear slightly improved. Cranial MR imaging demonstrated fresh small infarcts in the right cerebellar tonsil, the left cerebellar medulla, and the left middle cerebellar peduncle. MR angiography demonstrated an occlusion of the right vertebral artery. It is possible that reduced perfusion of the anterior inferior cerebellar arteries and internal auditory arteries on both sides resulted in multiple "border zone" infarcts and damage to the inner ear. Clinicians should be aware of the possibility of vertebrobasilar occlusive disease in case of sudden bilateral hearing impairment, even when brainstem or cerebellar signs are absent. PMID- 11218711 TI - Sexual dimorphism of the motoneurons in the human spinal cord. AB - There have been few morphometric studies on the size of the motoneurons of the human spinal cord. The purpose of the present study is to report the differences in the size of the motoneurons between males and females in the human spinal cord. We examined numbers and transverse cell body areas of the motoneurons of the anterior horn using 16 male and 21 female human spinal cords at levels C5 and L3. The sizes of the motoneurons were larger in males than in females, but their numbers were practically the same. These results can be of great importance in setting standard values for the understanding of morphological and functional correlations. PMID- 11218710 TI - Morphology of the dorsal lingual papillae in the bush dog (Speothos venaticus). AB - The dorsal lingual surface of a bush dog (Speothos venaticus) was examined by scanning electron microscopy (SEM). The tongue was about 7 cm in length. Filiform, fungiform and vallate papillae were found. The filiform papillae were distributed over the entire dorsal surface of the tongue. Each filiform papillae on the apical surface of the tongue had several conical processes, in the midportion were larger than those on the apex in size. In the region of the vallate papillae, the filiform papillae had not the conical processes and more larger than those on the midportion of the tongue. The fungiform papillae were present rounded bodies and more densely distributed on the tip of the lingual apex. There were 5 vallate papillae on both sides. The vallate papillae were located on both sides of the posterior end of the lingual body. Each papilla was surrounded by a groove and a crescent pad. In the dorsal surfaces of the papillae, small conical papillae were observed. PMID- 11218712 TI - Supraclavicular artery in Japanese: an anatomical basis for the flap using a pedicle containing a cervical, non-perforating cutaneous branch of the superficial cervical artery. AB - We investigated the morphology of the non-perforating cervical cutaneous branch in the lateral cervical triangle using 65 (130 sides) donated cadavers. We found the branch in 104 of the entire 130 sides (80.0%). In the majority (72.1%), the cutaneous branch did not cross the clavicle or acromion but supplied the dorsolateral cervical area. The branch was originated from the superficial cervical artery close to the posterior belly of the omohyoideus muscle and immediately lateral to the external jugular vein. The comitant vein, if present, drained into the external jugular vein. Our observations and measurements (length and diameter) suggested that the non-perforating cutaneous branch is useful for a pedicle of the dorsolateral cervical flap in Japanese people. However, detailed morphologies differ from the previous studies published in western countries. PMID- 11218713 TI - Anatomy and histology of the lacrimal fluid drainage system. AB - Five human specimens of the lacrimal canaliculus and sac were examined by light and scanning electron microscopy. The superior and inferior lacrimal canaliculi are lined with stratified squamous epithelium that is non-keratinized and non mucin-producing. The common canaliculus is also lined with stratified squamous epithelium, but its lumen is much narrower than the lumen of the superior and inferior canaliculi. The common canaliculus opens into an ample space called the vestibule, where the epithelium changes to high pseudostratified columnar and then low pseudostratified columnar. The vestibule continues to the infundibulum of the lacrimal sac. The infundibulum is formed by several epithelial folds that radiate from the vestibular opening to the lacrimal sac. The vestibule and infundibulum are consistent transitional structures from the common canaliculus to the lacrimal sac. The connective tissue of the lamina propria from the common canaliculus to the lacrimal sac has two histological characteristics: numerous free cell aggregates (= lymphoid structure) and numerous venules and capillaries (= cavernous structure). PMID- 11218714 TI - Morphological evaluation of the baboon hind limb muscles based on relative weight. AB - Morphological features of the hind limb muscles reflect the muscular function correlating with the locomotion. In this study, the muscles of the baboon hind limb were weighed and the relative muscle weights were compared with those of the human lower extremity. In the baboon, the biceps femoris was the largest (11.60%) and the vastus lateralis (10.67%) was placed second. The gluteus medius (8.55%) among the hip muscles and the gastrocnemius (4.38%) among the leg muscles were predominant in each segment. The relative weights of the gluteus medius and the biceps femoris were especially larger in the baboon than in the human, while the gluteus maximus and the soleus were larger in the human. The baboon gluteus medius and biceps femoris chiefly generate the propulsive power during quadrupedal locomotion and the human soleus is essential for the erect bipedalism. PMID- 11218715 TI - Fiber arrangement of the rat splenic capsule with special reference to elastic fibers. AB - The fiber arrangement of the rat splenic capsule was examined under scanning electron microscope (SEM) after selective removal by chemical maceration of capsule components, in conjunction with examination of thin sections using a transmission electron microscope (TEM). TEM findings were compared to those of the guinea-pig, mouse and dog. Serosal cells of the rat splenic capsule showed labyrinthic channels that consisted of expanded intercellular spaces and tunnel like spaces or slits in the basal cytoplasm. The channels contained fascicles of collagenous fibrils, forming a loose net on an underlying elastic lamina of densely aggregated elastic fibers. The fibrous tunica was an intermingled layer of elastic and collagenous fibers and sparse interstitial cells. The fibrous components were arranged more densely in the external layer than in the internal layer of the capsule. The elastic lamina comprised the outermost layer of the fibrous tunica in the intertrabecular region, but was situated deep in the trabecular region. Outward branches of the lamina in the trabecular region were arranged in a spiral. Intrachannel fibrillar fascicles were continuous, via fenestrations in the elastic lamina, with thick fascicles of collagenous fibers. The elastic lamina may play a role in effective contraction of whole spleen. In the guinea-pig, mouse and dog, elastic fibers were fragmented and not arranged in laminae. Typical smooth muscle cells were abundant in the dog. The channel spaces in the serosal tunica are discussed from the viewpoint of extravascular lymphatic flow for circulation of the peritoneal serous fluid. PMID- 11218717 TI - [For establishing geriatric medicine of the 21st century]. PMID- 11218716 TI - The effects of prenatal X-irradiation on hypoglossal nucleus: a GFAP immunohistochemical study. AB - The effects of prenatal X-irradiation on hypoglossal (XII) nucleus were investigated in the rat. Pregnant animals were exposed to a single whole body X irradiation on day 11 and 16 of gestation at a does of 1.3 Gy. The offspring were killed at 7-14 days of age for the histological and immunohistochemical observations. Nissl staining revealed no significant changes of XII motoneurons in these experimental animals. In the control case it was of interest that expression of glial fibrillary acidic protein-immunoreactivity (GFAP-IR) is largely confined to the dorsomedial region including the XII nucleus at the level caudal to the obex. Exposure of X-irradiation on day 16 of gestation led to similar expression of GFAP-IR in the nucleus at the same level. However, exposure on day 11 of gestation apparently led to strong expression of GFAP-IR in the XII nucleus at the level caudal to the obex and the expression was observed to extend rostrally. The GFAP-IR cells showed hypertrophy of cell bodies and longer cytoplasmic processes. Horse-radish peroxidase (HRP) injection into the tip of the tongue including the intrinsic muscles resulted in retrograde labeling in the ventromedial portion of the XII nucleus bilaterally from +0.30 to -1.25 mm. The present study would indicate that motoneurons of the XII nucleus supplying mainly the intrinsic and partly the extrinsic tongue muscles are more sensitive to X-ray exposure before the formation of the XII nucleus. PMID- 11218718 TI - [Perspectives of the aging science in the 21st century]. PMID- 11218719 TI - [Geriatric medicine of the 21st century--perspectives for the practice, education]. PMID- 11218721 TI - [Preventive geriatric standpoint of view for reducing the elderly people with disabilities]. PMID- 11218720 TI - [Basic concepts and strategies for the management of the elderly in the new era]. PMID- 11218722 TI - [Clinical stage of dementia of Alzheimer's type]. PMID- 11218723 TI - [Effective assessment and planning services for disabled older people]. PMID- 11218724 TI - [Care for the incurable elderly]. AB - The goals of medicine encompass the relief of pain and suffering, the promotion of health and the prevention of disease, and the cure of disease when possible and the care of those who can not be cured. Today, closely affiliated with various establishments, medicine sustains an influential but strange subculture in our society. Because of its insistent ideology for cure, medicine is blamed for futility, a misuse of modern technology. The root of the problem lies in the abandonment of the human soul when medicine in the 19th century joined the new sprung science which identified objectivity as a leading principle forbidding "cogito ergo sum". Accordingly, modern medicine neglected patients for whom the care of the mind is essential and failed to care for those with uncurable conditions. Curiously, the development of life sciences dictates the human soul as a final product of an evolution through a trade-off with aging and death. The human soul and its dignity must be revived at the heart of medicine, and the art of dying must be sought to enable a peaceful death. The concept of Tenju gann or "natural-end cancer", an example for blessed longevity followed by a peaceful death is an ideal goal of palliative care, developing the art of dying for every patient, irrespective of age or disease. Palliative care begins at the irreversible stage of diseases or when treatment impairs the dignity of a dying patient. With public disclosure physicians must be selected by aged patients and their families to promote the art of dying. PMID- 11218725 TI - [Discovery of cis-preference of aromatic N-methylamides and its application to molecular constructions]. AB - Aromatic secondary amides such as benzanilide (1) exist in a trans-amide form both in the crystal and in the solution, whereas N-methylbenzanilide (2) exists in cis form in the crystal, and predominantly in a cis form in the solution. Similar cis conformational preferences were observed in aromatic N,N' dimethylated ureas and guanidines, in which two aromatic rings are located face to face. The cis preferences of N-methylated amides, ureas and guanidines could be utilized to construct interesting aromatic architecture. N,N',N"-Trimethyl N,N',N"-triphenyl-1,3,5-benzenetricarboxamide (20) and a cyclic triamide (24) have crystal structures in which three N-phenyl groups direct to the same orientation (syn conformation). 1,2-Bis(N-benzoyl-N-methylamino)benzene (22), which have no fixed asymmetric center, afforded chiral crystals by simple recrystallization. Furthermore, aromatic multi-layered structures could be built and applied to obtain aromatic molecules which have potent DNA-binding ability. PMID- 11218726 TI - [Cytokine balance in the pathogenesis of rheumatoid arthritis]. AB - Rheumatoid arthritis (RA) is a common, frequently severe, chronic inflammatory disease. Although the cause of RA remains unknown, recent advances in understanding its pathogenesis have been substantial. Despite the use of a variety of medications, the treatment of RA is not fully effective in most patients. A T-helper type 1 (Th1)/T-helper type 2 (Th2) cytokine imbalance has been suggested to be of pathogenic importance in several diseases. In this review, the information of cytokine balance in both the experimental model of arthritis and patients with arthritis were summarized. Furthermore, to characterize the cytokine balance at a single cell level, we analyzed the subtypes of cytokine-secreting cells in an experimental model of arthritis using a dual color enzyme-linked immunospot assay (Stardust assay) which we newly developed. These information including our findings might provide us the clue for diagnosis and therapy of arthritis. PMID- 11218727 TI - [The amount of the loss of cyclosporine A dose correlated with the amount of leaching di (2-ethylhexyl) phthalate from polyvinyl chloride infusion tube]. AB - An interaction between cyclosporine A (CyA) injection and infusion tubes were examined. We used polyvinyl chloride (PVC) and polybutadiene (PB) tubes. CyA injection (Sandimmun) was diluted (0.495 mg CyA/ml) with saline and dripped through infusion tubes. The amounts of unsolved substances, loss of CyA dose and leached di (2-ethylhexyl) phthalate (DEHP) during the drip study were compared. CyA was not lost into the PB tube and no DEHP was leached. Therefore, using PVC tube, 11.9 mg of CyA were lost with in 24 h after the beginning of the administration, and the concentration of leached DEHP amounted to 93.6 micrograms/ml at 12 h. We also investigated the effects of the component of the einfusion solution on the loss of CyA into PVC tube using saline, electrolyte maintenance solution, 5% glucose and 10% maltose. Sugar-containing solutions were found to have less effects than other solutions on the loss of CyA dose and DEHP leaching. The leaching of DEHP may be a major factor for the generation of unsolved substances and the loss of CyA dose. In the clinical use of CyA injection, PB tube is the best selection and the sugar-containing solution is a second selection when PB infusion tubes are hard to obtain. PMID- 11218728 TI - [The trend of the drug eruptions in the last fifteen years]. AB - The drug eruptions are known to often become more severe by the readministration of causative drugs. It is an important theme to prevent the relapse of the drug eruptions. We have been monitoring drug adverse reactions at our hospital since October, 1980. We divided fifteen years from October, 1980 to September, 1995 into three periods; the first period (Oct., 1980-Sep. 1985), the second period (Oct., 1985-Sep., 1990), and the third period (Oct., 1990-Sep., 1995), and discussed the trend of the drug eruptions appeared among these three periods. The number of the drug eruptions increased. But the proportion to the total drug adverse reactions and to the number of patients slightly decreased. The eruptions in women much increased and in the patients of forties or older generations also increased. But in patients of thirties or younger generations decreased. While nonsteroidal anti-inflammatory drugs (NSAIDs) other than pyrines, antibiotics other than penicillins and cephalosporins and drugs affecting the cardiovascular system and the metabolism tend to increase, pyrines, penicillins, iodic and biliary contrast media tend to decrease. The incubation period before the eruption appeared is less than three days in most antibiotics and anti inflammatory drugs. But it is more than four days in most drugs for chronic diseases. Other symptoms such as nausea, fever and liver dysfunction were shown in 9.2% of the drug eruptions. In 8.9% of the drug eruptions a relapse of allergic reactions included eruptions were also found. In some cases the drug eruptions exacerbate by re-administration of beta-lactam antibiotics. In the case of administration of drugs, it is necessary to pay attention to dermatitis caused by the drugs. And we recognized the importance of the system for the prevention of the relapse of drug eruptions including injections. PMID- 11218729 TI - Effects of sho-saiko-to (xiao chai hu tang), a Chinese traditional medicine, on the gastric function and absorption of tolbutamide in rats. AB - This study was carried out to investigate the effects of Sho-saiko-to (Xiao Chai Hu Tang), a Chinese traditional medicine, on the gastric function including the gastric emptying rate (GER) and intragastric pH in rats. Additionally, the effects of the GER and intragastric pH on tolbutamide absorption after oral administration were examined. The GER measured at 40 min after dosing was reduced to about 70% by the pretreatment of Sho-saiko-to (500 mg/kg). The plasma tolbutamide concentration in the rats treated with a 250 mg/kg dose of Sho-saiko to was significantly lower than that in the control group. Plasma tolbutamide concentrations increased along with the GER in the group co-administered Sho saiko-to, and there were significant correlations between the GERs and plasma levels in both time points at 20 and 40 min after administration. In the study using pylorus-ligated rats, Sho-saiko-to significantly elevated the intragastric pH, but induced no change in the concentrations of tolbutamide dissolved in the gastric content. Additionally, Sho-saiko-to did not change the area under the plasma concentration-time curve (AUC) of tolbutamide up to 60 min after administration into the stomach loop, and gastric absorption has been considered to minimally contribute to whole absorption of tolbutamide in the gastrointestinal tract. These results indicate that Sho-saiko-to has an inhibitory effect on the function of gastric emptying in rats. The reduced gastric emptying could affect gastrointestinal absorption, resulting in the lower plasma concentration of tolbutamide after oral administration. Furthermore, it is suggested that Sho-saiko-to can raise the intragastric pH but affect neither the intragastric dissolution nor the gastric absorption of tolbutamide. PMID- 11218730 TI - [Enhancing effect of switching iontophoresis on transdermal absorption of glibenclamide]. AB - Glibenclamide(GLI) is widely used as an oral hypoglycemic drug in the treatment of non-insulin dependent diabetes mellitus (NIDDM). We investigated The enhancing effect of switching iontophoresis on the transdermal absorption and reduction of skin irritation to develop a transdermal dosage form of GLI. The 0.1% of Gli suspensions in 0.2 M tris-HCl buffer of pH 7.4, 8.0 and 8.5 were prepared as donor solutions. We examined drug permeation through the excised rat abdominal skin, drug absorption in rats and reduction of skin irritation after application of switching iontophoresis for 1 h using DC 10 V. The solubility of GLI in 0.2 M tris-HCl buffer increased with a rise in pH. In the permeation study, GLI was permeated continuously and the cumulative amount of permeated GLI increased using an alkaline donor solution. In the drug absorption study, the application group of pH 8.5 gave higher plasma concentration levels than those of pH 7.4 and 8.0 groups. The skin irritation evoked by the application of iontophoresis was pathologically studied. A total irritation score (TIS) was estimated as a judging standard for the skin damage. The TIS value increased dependently with a rise in pH. However, it was considered that the skin irritations were not serious and small matters. The results demonstrate the possibility of iontophoretic transdermal administration of GLI and the effect of drug solubility in the donor solution on the absorption of GLI. PMID- 11218731 TI - [Inhibition effect of Amaryllidaceae alkaloids, lycorine and lycoricidinol on macrophage TNF-alpha production]. AB - We previously demonstrated that Amaryllidaceae alkaloids, lycorine and lycoricidinol, inhibit induction of apoptosis by calprotectin derived from neutrophils, and that the latter alkaloid showed suppression in rat adjuvant induced arthritis model. These findings suggest that the alkaloids have a modulating activity against inflammatory reaction. To explore further the mechanism of the suppression for inflammation, we studied the effect of the alkaloids on macrophage tumor necrosis factor (TNF-alpha) production in vitro, since TNF-alpha is recognized as a pivotal cytokine to regulate inflammation. As a result of this study, lycorine and lycoricidinol inhibited TNF-alpha production of murine macrophages stimulated with lipopolysaccharide (ID50 were 0.2 microgram/ml and 0.002 microgram/ml, respectively). The inhibition was also observed in macrophages treated by Gram-positive bacteria, Enterococcus faecalis. Both lycorine and lycoricidinol reportedly have inhibitory activity for protein biosynthesis. Although the inhibition of TNF-alpha production by lycoricidinol was mainly due to the inhibition of protein biosynthesis, lycorine showed inhibition against TNF-alpha production at lower concentrations than the case that they inhibited 35S-Cysteine/35S-Methionine incorporation into macrophages. These facts suggest that the inhibition of TNF-alpha production is not due to the inhibitory activity against protein translation at least at lower concentrations. From these results, it was concluded that these alkaloids exert inhibitory effects not only on neutrophil apoptosis-inducing protein, calprotectin, but also on macrophage TNF-alpha production. PMID- 11218733 TI - Evaluation of the effective drugs for the prevention of nausea and vomiting induced by morphine used for postoperative pain: a quantitative systematic review. AB - Postoperative nausea and vomiting (PONV) with morphine therapy develops in more than 60% of patients after surgery, markedly reducing patient QOL. The prophylactic effect of several antiemetics has already been studied, but evaluations, and even those using the same drug, are not uniform. The present research involved a meta-analysis of randomized controlled trials on prophylactic drug therapy for PONV in patients receiving morphine for the treatment of postoperative pain. The efficacy of the prophylactic administration of the drugs was examined. As a result, meta-analysis of five drugs was possible and the evidence of efficacy was shown for three drugs ranked in order of an increasing odds ratio (OR) and confidence interval (CI): dexamethasone (OR: 0.23, 95% CI: 0.15-0.35, p < 0.00001), droperidol (OR: 0.27, 95% CI: 0.21-0.34, p < 0.00001), and metoclopramide (OR: 0.48, 95% CI: 0.30-0.75, p < 0.001). These results suggest that the three drugs are effective in prophylactic treatment for PONV. Of them, dexamethasone used as a prophylactic drug for PONV provided the best results. Dexamethasone was shown to reduce the incidence of PONV from 66-80% to 16-50% with a dose of 1.25 to 10 mg and to be suitable as a first drug of choice. PMID- 11218732 TI - [The effects of kampo-formulation and the constituting crude drugs, prescribed for the treatment of peptic ulcer on H,K-ATPase activity]. AB - We studied the effects of 17 kinds of Kampo-formulations prescribed for the treatment of peptic ulcer on H,K-ATPase activity. The activity was strongly inhibited by San-o-shashin-to ([symbol: see text], IC50 = 82 micrograms/ml), Bukuryo-in ([symbol: see text], IC50 = 110 micrograms/ml), Shakuyaku-kanzo-to ([symbol: see text], IC50 = 170 micrograms/ml), Hange-koboku-to ([symbol: see text], IC50 = 290 micrograms/ml), Dai-saiko-to ([symbol: see text], IC50 = 340 micrograms/ml), Irei-san ([symbol: see text], IC50 = 380 micrograms/ml) than other Kampo-formulations. Among the 17 kinds of crude drugs contained in these Kampo-formulation, Rhei Rhizoma, Coptidis Rhizoma, Glycyrrhiza Radix, Cinnamomi Cortex, and Poria have notable inhibitory effects (IC50 = 19-57 micrograms/ml). H,K-ATPase activity was inhibited by sennoside A (Rhei Rhizoma), sennoside B (Rhei Rhizoma), ergosterol (Poria), coptisine (Coptidis Rhizoma), glycyrrhizin (Glycyrrhiza Radix), glycyrrhetic acid (Glycyrrhiza Radix), gallic acid (Cinnamomi Cortex) in the 21 components of these crude drugs (IC50 = 1.6-7.9 x 10(-4) M). The inhibition of San-o-shashin-to and Bukuryo-in is considered to be mainly attributed to Rhei Rhizoma and Poria, respectively. The anti-gastric ulcer effects of San-o-shashin-to and Bukuryo-in may be ascribed to the inhibition of H,K-ATPase activity. PMID- 11218734 TI - Medication management skill and regimen compliance are deteriorated in the elderly even without obvious dementia. AB - We investigated whether regimen comprehension deteriorated in the elderly patients who did not suffer from obvious dementia. Eligible patients were ambulatory elderly patients who did not show any signs of dementia and could visit our outpatient clinic by themselves. 138 patients (age: 43-89, 75 males and 63 females, underlying diseases: hypertension, hyperlipidemia, arrhythmia etc.) were tested with a regimen comprehension scale (RCS: Jpn J Geriat 1997; 34: 209 214). The differences in scores among individuals increased with age. Scores of 5 or less in the RCS were recorded in 10 out of 69 patients aged 65 or more, but no such scores were recorded in younger patients (p < 0.01). The 60 patients who scored less than full marks were classified into two groups, the T-group (tutored by pharmacists), and a Non Tutored group. RCS was tested again in both groups. Only in the T-group (n = 28), did the second scores increase significantly (from 7.2 +/- 0.9 to 8.6 +/- 2.0 (m +/- SD); p < 0.01) after tutorial by pharmacists. Comparing the 7 patients who obtained an RCS score of 5 or less and age- and gender-matched controls who got full marks, there was no difference in the HDS-R test. These results suggest that even in elderly patients who did not show any signs of dementia, the regimen comprehension deteriorated with age, and tutorials in medication protocols were considered to be effective. PMID- 11218736 TI - [Approaches to sella turcica in endoscopic pituitary surgery]. AB - Recent advances in endoscopic sinus surgery suggested the potential for its surgical application to pituitary surgery. A number of institutions have reported the advantage of endoscope use in pituitary surgery, which is now widely accepted, but approaches to the sella vary in the literature. We retrospectively studied sella approaches in endoscopic pituitary surgery as rhinologists. Subjects included 6 cases of pituitary adenoma and 2 cases of Rathke's cleft cyst. A both-nostril transnasal transsphenoidal approach, our standard technique, was used in 6 cases. This approach consisted of elevation of mucoperiosteal flaps, resection of the vomer and sphenoid anterior wall, and opening of the sellar floor. Elevated mucoperiosteal flaps were used to close of the sella after tumor resection. All tumors were removed and no significant postoperative complications occurred. We found the both-nostril transnasal approach to be easy and time-saving and provided surgeon with a broad surgical field necessary to treat large tumors and accidental cases. Postoperative observation of the sella was easy for wide opening of the anterior wall of the sphenoid sinus. In our experience with reoperation, we quickly accessed the sella and easily removed tumors in the second operation. Our technique therefore has an advance in treatment of recurrence. The both-nostril transnasal approach involves the same procedures as median drainage of the sphenoid sinus, so our technique may have advantages in preventing mucocele of the sphenoid sinus as a late complication of transsphenoidal surgery. The transnasal transsphenoidal approach via both nostrils is preferable rhinologically. PMID- 11218735 TI - [Micelle-mediated extraction for concentrating conjugated bilirubin in urine]. AB - An extraction method based on the phase separation of aqueous micellar solutions of n-octyl-beta-D-thioglucoside (OTG) was applied to the concentrating conjugated bilirubin in urine. The analyte in sample solutions could be efficiently concentrated into a small volume of surfactant-rich phase, while hydrophilic matrix components including urinary protein, ascorbic acid, and saccharide remained in the aqueous phase. The concentrated OTG negligibly affected the diazo reaction and the subsequent spectrophotometric detection. Conjugated bilirubin was successfully determined in the concentration range from 0.05 microgram/ml to 5 micrograms/ml with a 96-well microplate reader absorption spectrophotometer. PMID- 11218737 TI - [Congenital rubella syndrome developing after a 1987-1988 epidemic in Japan]. AB - Since vaccination legislation was revised in 1994, rubella vaccination has been changed from application to all junior high school girls with no history of clinical rubella to application to individual infants and junior high school students. This may decrease the vaccination acceptance rate and increase the chance of pregnant women's infection with rubella causing congenital rubella syndrome (CRS). We studied 5 children with CRS developed after a 1987-1988 epidemic in Japan to determine how their mothers were infected, and reviewed auditory findings. They were CRS-confirmed or CRS-compatible cases who met CRS diagnostic criteria formulated by the U.S. Center for Disease Control (CDC) in 1983. Two mothers had not been vaccinated because this was not legislated when they were in junior high school. Three were eligible for vaccination at 14, but 2 were not vaccinated. The children were born in 1991-1997. Complications were low birth weight in 3, delay in neck stabilization in 2, and cataract in 1. No case was serious. Ages at first ENT examination ranged from 3 months to 1 year and 8 months. ABR showed hearing loss of > or = 90 dBnHL. They started using hearing aids at 6 months to 1 year and 10 months. Tsumori mental development tests showed delays in developmental age in 2 who started auditory training after ages of 1 year and 6 months. Findings indicated that infants, students, and potentially pregnant women should be vaccinated. Complete serologic testing are important in pregnant women and fetal rubella infection should be diagnosed early by PCR. PMID- 11218739 TI - [Clinical features of benign paroxysmal positional vertigo]. AB - Our understanding of the pathomechanism of benign paroxysmal positional vertigo (BPPV) has improved dramatically. A type of BPPV featuring mixed torsional and vertical nystagmus induced by the Dix-Hallpike maneuver involves the posterior semicircular canal (P-BPPV). The other type of BPPV featuring horizontal nystagmus induced by spine-to-lateral head positioning involves the horizontal canal BPPV (H-BPPV). In complaints of vertigo or dizziness, 619 patients visited our department last year. Of these, 142 (23%) was had positional nystagmus consistent with a diagnosis of BPPV, 118 (19%) had no nystagmus but were suspected of BPPV due to vertigo episodes. BPPV was the most frequent diagnosis. H-BPPV was not rare, but accounted for 30% of BPPV. Of H-BPPV, 73% featured direction changing geotropic nystagmus, and 27% direction changing apogeotropic nystagmus. H-BPPV resolved faster than P-BPPV. Most cases caused by head trauma were P-BPPV. Transition between P- and H-BPPV was found in 6 cases. Women outnumbered men by about 3 to 2 in both P- and H-BPPV. Peak incidence was found in the those in their 60s and 70s, suggesting that the etiologies of both types of BPPV are essentially the same. PMID- 11218740 TI - [Radiation therapy for head and neck cancer]. AB - Radiation therapy is the first choice of treatment for most of the early squamous cell carcinoma of the head and neck. Conventional radiotherapy however, contributes to the high local control rates only for carcinoma of the glottic larynx and the nasopharynx. Squamous cell carcinoma of the other sites cannot be sterilized easily only by external beam radiation therapy alone. Chemoradiotherapy, conformal three-dimensional radiotherapy and multi-daily fractionation are introduced clinically to improve local control and/or survival for radioresistant tumor. In this review, consensus report of radiation therapy for carcinoma of the larynx and pharynx, which was reached an agreement in JASTRO meeting in 1998, is introduced. The role of radiation therapy in the management of head and neck cancer in present and near future is also discussed. PMID- 11218738 TI - [Evaluation of nasal valve by CT imaging]. AB - The nasal valve was studied using coronal scans by computed tomography (CT). SUBJECTS: Coronal images were 5 mm thick obtained from 133 subjects 93 men and 40 women averaging 46 years of age. METHODS: The valvular area was studied in 2 slices containing nasal valve, anterior and posterior slices 5 mm apart. After defining standard points for evaluation, breadth, height and area were evaluated using NIH Image Version 1.59 from left and right as an unit. RESULTS: Results were follows: 1. The breadth of the nasal valvular area is larger in men than in women, and the height greater. The angle of valvular area is similar in both. 2. A comparison of anterior and posterior slices showed the smallest breadth of valvular area in the anterior slice to be smaller than in the posterior slice. The breadth of the vestivular area below the valvular area is larger in the anterior than posterior slice. The angle in the anterior slice is larger than that in the posterior slice. The area of valvular area in the anterior slice is smaller than that in the posterior slice. PMID- 11218741 TI - [Evaluation of computer-assisted diagnosis of small pulmonary nodules using contrast-enhanced dynamic helical CT]. AB - Dynamic helical computed tomography(DH-CT) was performed to examine 45 lesions(23 lung cancers, 2 pulmonary metastasis, and 20 benign nodules) as an application of computer-assisted qualitative analysis of small pulmonary nodules. Based on the three-dimensional(3D) CT image data, the internal structure of the nodule was assessed quantitatively and temporal changes were evaluated. The entire lesion was examined by helical scanning with a beam width of 2 mm(pitch of 1) before contrast enhancement and 2 and 4 minutes after contrast enhancement. Using the digital CT data, the pixels inside the nodules were quantified based on a combination of CT values and 3D curvature in order to differentiate between benign(BN) and malignant nodules (MN). (The numeral score abovementioned was calculated.) The average scores for BN 2 and 4 minutes were -5.72 and -12.8, respectively, and those for MN were 5.51 and 12.0, respectively(p < 0.01). Assuming that a score of 0 or higher indicates a MN based on the CT data 4 minutes. In conclusion, 3D computer-assisted analysis of the internal structure of small pulmonary nodules using contrast-enhanced DH-CT was found to be effective for differentiating between benign and malignant nodules. PMID- 11218742 TI - [Usefulness of transradial angiography and interventional angiography for abdominal diseases: comparison with transfemoral or transbrachial approach]. AB - Transradial angiography has recently emerged as an alternative to the transfemoral or transbrachial approach, especially for coronary or cerebral procedures. However, there are few such studies regarding abdominal angiography. In our institution, we performed abdominal angiography and intervention by the transradial arterial method in 42 cases using a 120-cm-long 4 Fr catheter and compared the results with the transfemoral or transbrachial arterial method and examined the usefulness of this technique. Puncture was successfully carried out in 42 cases, whereas failure occurred in one case, in which the transbrachial method was adopted because of weak pulse. Selective catheter insertion was successful in all cases, after the shape of the catheter had been improved. No serious or dangerous complications occurred during the examinations. In addition, many patients chose the radial arterial method for subsequent examinations on a questionnaire survey we gave patients on the day after we did abdominal angiography by the transradial arterial method. We consider that the transradial arterial method can be used generally in angiography and interventional angiography for abdominal diseases. PMID- 11218743 TI - [Development and assessment of real cardiac motion simulation phantom]. AB - To evaluate cardiac images obtained by multi-slice CT, assessments of the temporal resolution and reconstruction algorithm are essential. For these purposes, we have designed and developed a cardiac motion phantom. Using suitable driver sequences, the phantom allowed for modeling of real left ventricular motion, which was characterized by fast pumping, slow pumping, fast filling and slow filling. Our phantom seems to be useful for use in the fundamental assessments and researches of cardiac CT. PMID- 11218744 TI - [Significance of CT findings and catecholamine determination in peripheral blood of asymptomatic pheochromocytoma and paraganglioma]. AB - The purpose of this study was to assess the CT findings and significance of hormone determination in the peripheral blood of asymptomatic patients with pheochromocytoma and paraganglioma. CT findings in 29 patients with surgically proven pheochromocytoma(n = 19) and paraganglioma(n = 10) were reviewed. Nine patients(31%) were symptomatic and 20 (69%) were asymptomatic. Tumor size ranged from 39 mm to 114 mm(mean: 60 mm) in symptomatic patients and 11 mm to 100 mm(mean: 50 mm) in asymptomatic ones. Of the 9 symptomatic patients and 18 asymptomatic patients, a homogeneous solid pattern was seen in 4 and 4, mixed pattern in 2 and 6, and massive necrotic pattern in 3 and 8 patients, respectively, on CT scans. The CT attenuation values in symptomatic cases ranged from 30 HU to 50 HU(mean: 41 HU) on precontrast CT scans and 60 HU to 111 HU(mean: 77 HU) on postcontrast CT scans, while those in asymptomatic cases ranged from 15 HU to 48 HU(mean: 33 HU) on precontrast CT scans and 66 HU to 133 HU(mean: 95 HU) on postcontrast CT scans. There were no statistically significant differences in tumor size, homogeneity, or CT attenuation values between symptomatic and asymptomatic patients. All symptomatic patients and 17(89%) of 19 asymptomatic cases showed elevated levels of catecholamine (epinephrine) or norepinephrine in the peripheral blood. Our study showed that the CT findings in asymptomatic patients were similar to those in symptomatic patients, and 89% of asymptomatic patients showed elevation of catecholamine in the peripheral blood. Determination of catecholamine level in the peripheral blood is recommended for preoperative diagnosis in patients suspected of having asymptomatic pheochromocytoma or paraganglioma on CT scans. PMID- 11218746 TI - [Diagnostic imaging in the congenital and developmental disorders: before and after advancement of molecular genetics]. AB - In this review, a general approach to the congenital and genetic disorders is presented. Differentiation between deformation and malformation is practically important to triage congenial or developmental abnormalities. The disease distribution along arterial supply or sclerotome is more suggestive of developmental or acquired disorder, either in utero or in early infancy. Newly developed genetic analysis of bone dysplasia is an important subject, and this review focuses on collagen abnormalities, systemic disorders associated with neoplasms and receptor disorders. Owing to the progress of molecular genetics and gene therapy, the approach to hereditary conditions will dramatically change. Although most of these diseases are relatively uncommon, the role of diagnostic radiologist may become more important for early institution of treatment planning and estimating prognosis. PMID- 11218745 TI - [Visualization of abdominal arteries by super-high-flow venous injection using multidetector helical CT]. AB - The purpose in this study was to compare the ratio of visualization of upper abdominal arteries using MDHCT between the super-high-flow injection method (Group A) and the conventional injection method (Group B). The subjects ects were 200 patients who were randomly divided into Group A (100 patients) and Group B (100 patients). In Group A, visualization of the large arteries, including the CE, SMA, HA and LGA, was possible at a rate exceeding 96%, and that of the small arteries, including the DPA, SPDA, RGA and Cyst A, was more than 79%. Visualization of upper abdominal arteries was markedly improved by the super high flow injection technique. PMID- 11218749 TI - [Tracing of analysis and prophylaxis on medical malpractice in Japan]. AB - The role of drugs, especially injectables, in medical treatment is extremely important. In Japan, accidents associated with injections were not uncommon. Post injection neuroparalysis of the radial nerve and sciatic nerve was associated with problems in textbooks, which described injection sites at the regions of neural passage. Then, in the 1970s, quadriceps femoral muscle contracture and deltoid muscle contracture became a social problem. When the author examined the osmotic pressure of various injectables, some injectables were found to deviate from the physiological range. When 335 injectables were evaluated for the potential to cause hemolysis, many injectables marketed for intramuscular injection gave strong hemolytic reaction, which attracted attention. Next, 89 types of injectables were tested for the potential to cause muscle damage by injecting into the femoral muscle of rabbits, and severe muscular damages were observed with antipyretics, analgesics, and antibiotics. The group lawsuit of Yamanashi Prefecture was settled at the Tokyo High Court in 1989, with the pharmaceutical company agreeing to pay over 2.95 billion yen as settlement. Giving drugs to patients occupies an important place among medical act. Medical disputes concerning accidents of wrong drugs and wrong usage are common. Obviously health care workers should exercise great caution in their duties, but without measures taken against medical equipment and drugs, such as containers and seals, this type of accidents will not be reduced. Through giving numerous speeches and lectures on medical accidents throughout the years, the author had felt strongly the need for teaching materials such as video tapes that can be used for self-learning. In 1999, the video entitled "Medical Accident-Learning from Actual Cases-" was finally completed, which consists of 6 parts (1. General consideration, 2. Blood transfusion, 3. Drug administration, 4. Surgery, 5. Examinations, 6. Management). For each area, typical incidents are presented as reproduced video taping. Then the criminal responsibility, civil responsibility and administrative responsibility of the doctor or nurse concerned are questioned in the form of questionnaires. Subsequently, the author also published a commentary book for the video that provides commentaries of the cases. PMID- 11218748 TI - [Studies on distribution of H type 1-H type 4 antigens of ABO system and on FUT2 polymorphism]. AB - I have examined the immunohistochemical distribution of H type 1-H type 4 antigens of the ABO system in human submandibular gland using either of the three anti-H monoclonal antibodies specific for H type 1, H type 2 and H type 3/4. I have clearly identified cell types expressing H type 1, H type 2 and H type 3/4: H type 1 in mucous cells and duct cells, H type 2 in duct cells, and H type 3/4 in serous cells of the submandibular gland. The expression of H type 1 and H type 3/4 in the human submandibular gland is regulated by the Se enzyme. The FUT2 encodes Secretor type alpha(1,2) fucosyltransferase (Se enzyme), which regulates the expression of ABH antigens in the gastrointestinal tract and secretions. Molecular analysis of the FUT2 polymorphism of various populations have indicated the ethnic specificity of null alleles: the null allele se428 is a common Se enzyme deficient allele in Africans and Caucasians but does not occur in Asians, whereas the null allele se357,385 is specific to Asians. The gene frequency of se428 or se357,385 is about 0.5 in each respective population. Why the se428 is absent in Asians is of interest. PMID- 11218747 TI - [Colonic varices; a case report]. AB - Colonic varices is a rare entity that is caused by portal hypertension in most instances. In the case reported here, barium enema and colonoscopy showed multiple tortuous polypoid lesions with intact mucosal surface. Inferior mesenteric angiography showed arteriovenous malformation in the sigmoid colon, complete obstruction of the inferior mesenteric vein, and tortuous dilated marginal veins. We assume that the colonic varices of this case was secondary to complete obstruction of the inferior mesenteric vein following AVM of the sigmoid colon. Close follow-up should is warranted in cases of colonic varices because of the risk of bleeding. PMID- 11218750 TI - [From medicolegal toxicology to forensic toxicology]. AB - The importance of forensic toxicology has been increasing until now, because of the increasing numbers of toxic substances and poisoning incidents. In Japan, a special translational word "houi-chudoku-gaku" has been used for the forensic toxicology especially in the field of legal medicine. The Japanese word, however, does not seem appropriate for translation of forensic toxicology, because it covers medicine, pharmacy and police sciences interdisciplinary. In 1980, Emeritus Prof. Hidetoshi Yoshimura created an appropriate word "hochudoku-gaku" for translation of forensic toxicology. In 1982, Prof. Yoshimura and his friends established the Japanese Association of Forensic Toxicology, consisting of people from legal medicine, pharmacy and police institutes. This Association enabled lively discussions among different fields and greatly contributed to advances of forensic toxicology in Japan. We started studies of forensic toxicology using gas chromatography (GC)/mass spectrometry (MS) in 1979. Until now, we delt with solid phase extraction (1987-1994), surface ionization GC (1989-1997), negative ion chemical ionization MS (1981-now), solid-phase microextraction (1994-now), cryogenic oven trapping GC (1997-now), surface ionization organic MS (1998-now) and high-performance liquid chromatography/tandem MS (1998-now). In this review, the author presents some details of solid-phase microextraction, negative ion chemical ionization MS, cryogenic oven trapping GC and surface ionization organic MS. Unprecedented poisoning terrorism by use of sarin took place in Matsumoto and Tokyo in 1994 and 1995, respectively. On July 25, 1998, a curry poisoning incident using arsenious acid occurred in Wakayama, resulting in the death of 4 people and injury of 63 people. Since then, more than 30 imitative poisoning cases have been reported by mass communication within 1 year. In spite of the above continuing poisoning cases, almost no effective measures have been taken by the administration of our country and local governments. Many serious problems concerning poisoning and drug abuse are accumulating in Japan. In this review, the problems are also made manifest, and some proposals are presented to solve the problems. PMID- 11218751 TI - [The dynamics of cytokines and their related substances in skin wounds]. AB - Molecular-pathological study on cytokines and their related substances in skin wound healing was performed from the view points of forensic pathology; 1. The dynamics of inflammatory cytokines such as interleukin (IL)-1 alpha, IL-1 beta, IL-6 and tumor necrosis factor-alpha (TNF alpha) during murine wound healing was examined at the levels of protein and mRNA. As for the results, the production of those inflammatory cytokines could be considered as one of the local vital reactions after wounding, and it was clarified that those inflammatory cytokines were one of the biological markers for forensic wound age determination. Practically, our immunohistochemical and morphometrical study with human skin wounds with different wound ages suggested that the ratios of IL-1 alpha-positive cells, considerably exceeding 30%, indicated a postinfliction interval of 1 day or less. 2. In mouse skin incision, a significant increase in IL-10 mRNA occurred between 30 and 180 min. The increased expression of IL-10 mRNA could be considered a vital reaction in skin wounds. Furthermore, it was clarified that IL 10 may have an important regulatory role in limiting the extent and duration of inflammatory response during skin wound healing. 3. Fas and Fas ligand (Fas L) were immunohistochemically detectable on macrophages and fibroblasts in skin wound healing process. Morphometrically, the number of cell expressing Fas and/or Fas L reached a peak at 6 days after wounding. Therefore, it is considered that apoptosis through Fas and Fas L may play an important role for reducing the cellularity during proliferative phase of wound healing in mice. PMID- 11218752 TI - [Membrane disorder and free radical]. AB - The aim of this study is to confirm cholesterol-derived hydroperoxides in membrane lipids as indices of free radical or active oxygen-induced membrane disorder or pathological changes at legal medicine. First, 7 alpha- and 7 beta hydroperoxycholesterol (7 alpha-OOH and 7 beta-OOH) were synthesized. Then, these were identified in lipids from human fatty liver by liquid chromatography-mass spectrometry. Secondly, the method for quantifying 7 alpha-OOH and 7 beta-OOH by high-performance liquid chromatography with chemiluminescent detection (HPLC-CL) was developed. Finally, the following membrane disorders were examined based on lipid peroxidation. Elevated lipid peroxidations were found in erythrocyte membranes of alcoholic patients, in alcoholic fatty liver, and in muscle of alcohol dosed rats. Enhanced lipid peroxidation was induced in rat kidney by paraquat. In addition, lipid peroxidation was increased in brains of senile dementia as well as in atheroscleroic plaque. Thus, we confirm 7 hydroperoxycholesterol as a marker of free radical-induced oxidative stress. PMID- 11218753 TI - [Forensic pathological significance of iNOS with regard to brain and myocardial damage]. AB - Inducible nitric oxide synthase (iNOS) does not express within cells under normal conditions. But, it is induced by inflammatory cytokines and the activity of iNOS is independent of elevated Ca2+. It is implied that nitric oxide (NO) produced by iNOS has a close relation with pathological conditions as a mediator of cell damages. We aimed at the crucial property of iNOS, therefore we have searched the expression of iNOS for the purpose to establish forensic pathological significance in the cases with damages of neuronal cells or cardiomyocytes. At first, we examined induction and expression of iNOS in the human brains whose causes of death was traumatic brain injury (TBI). These findings demonstrated prolonged induction of iNOS in neutrophils, microglia/macrophages, and vascular smooth muscle cells in traumatized brain. Such a response may indicate that iNOS could play a crucial role on cerebrovascular disturbances and secondary brain injury subsequent to TBI. Secondly, we evaluated the induction and expression of iNOS in the human hearts with myocardial cell damage. The expressions of iNOS were localized to the following areas, the cardiomyocytes in the zone adjacent to the infarcted area, the preserved cytoplasm of infarcted cardiomyocytes, the endothelial cells in arteriolar walls and macrophages in viable myocardium. These findings have led to the speculation that the NO might play a significant role during myocardial ischemia and reperfusion. Furthermore, representative expression of iNOS was identified in coronary artery, that is the portion of shoulder and broken part of coronary atherosclerotic plaque. These findings may indicate that the iNOS might have a close relation to the coronary atherosclerotic lesion. The physiopathological mechanism of iNOS might involve in the close relation with inflammatory cytokines. The precise elucidation of this participation may make it possible to explicate the presumed time of injury in an earlier stage, and to clarify the forensic pathological significance of these inflammatory factors. PMID- 11218754 TI - [The role of heat shock proteins on the disordered tissues: implication for the pathogenesis and diagnostics in the forensic practice]. AB - There are many problems in identifying the cause of death from the early acute myocardial infarction and hypothermia in the field of forensic medicine, because there are no clear findings to identify without details of circumstances. It was caused complexly by many factors such as health condition, age, surroundings, weather, alcohol drinking, drugs poisoning, etc., and unfortunately the early acute myocardial infarction and hypothermia invasion almost never show the vital reactions. A variety stresses especially ischemia and temperature induce the expression of heat shock proteins (Hsp), and previous reports have documented the function and regulation of Hsp expression. Hsp are currently classified into five groups on the basis of size. Of these, the 70 Kd Hsp (Hsp70 family) are regarded as most important proteins because they are most often highly induced in stressed cells. In the field of medical science, various diseases induce the expression of Hsp and especially Hsp70 family are well related to some diseases. Of course, previous report in the field of forensic medicine demonstrated that hypoxic/ischemic neuronal damage induced the expression of Hsp70 in the brain of forensic autopsy cases and suggested that investigation of Hsp70 could be effective for diagnosing hypoxic/ischemic neuronal damage during process of death. So we investigated the expression of Hsp70 induced by the lethal ischemia and hypothermia in the experimental rat model and practical autopsy cases. The present study suggests that the lethal ischemia induce the expression of Hsp70 in the heart and the lethal hypothermia induce the expression of Hsp70 in the cerebral cortex, and these inductions are one clear findings contributing to the estimate the cause of death from the acute myocardial infarction or lethal hypothermia in the forensic autopsy cases. PMID- 11218755 TI - [Significance of product documents (tenpubunsho) cited in judicial precedents in the field of anesthesiology]. AB - The significance of the product documents (Tempubunsho) was mentioned in 21 out of 94 medical malpractice cases published in several laws reports 1963-97. The number of such cases has been increasing in recent years. Among the items described in the product documents, the precautions for use were most frequently mentioned (12 cases) followed by the instructions for administration and dosage (3 cases). In most cases, the judgment was against the medical institution involved due to the violation of legal obligations with respect to the contents of the product documents. Product documents will be taken much more seriously in future lawsuits. Attention should be focused on the contents of the product documents, especially when revised. When the administration of a drug deviates from the contents of the product document, medical evidence is required to support this deviation. PMID- 11218756 TI - [Genotyping of blood-groups by denaturant gradient gel electrophoresis (DGGE)]. AB - The denaturant gradient gel electrophoresis (DGGE) method was used in order to simultaneously estimate the genotypes of different factors in a gel plate consisting of one sheet. A genotype analysis of the blood groups (MN, Duffy, Kidd type) and serotype (Gc system) was carried out. DNA samples extracted from the leucocytes of volunteers, whose blood group had already been proven, were used. The PCR amplification fragments were amplified from the gene which controlled each blood group. The primers were designed in order to analyze genotypes with from 1-3 base substitutions in the amplification product. The concentration of the denaturant most suitable for the DGGE method to detect each genotype of the blood groups (MN, Duffy, Kidd type and Gc system) was calculated using a computer simulation method. The denaturant concentration limit of the gel which was suitable for performing a DGGE analysis was determined to range from 15-36%. Electrophoresis was performed at 60 degrees C and with 100 V using this gel on each amplification fragment for 3 hours. The gel after electrophoresis was treated in ethidium bromide in order to detect the DNA band. The genotype (M/M, M/N and N/N) of the MN blood group, the genotype (Fya/Fya, Fya/Fyb and Fyb/Fyb) of the Duffy blood group, the genotype (Jka/Jka, Jka/Jkb and Jkb/Jkb) of the Kidd blood group and each allele (GC*1S, GC*1F and GC*2) of the Gc system were all simultaneously distinguished in one plate. As a result, it was possible to estimate multiple gene polymorphism, while substituting bases 1-3, by PCR, DGGE and ethidium bromide staining. The polymorphic results obtained using this DGGE method is very useful for cases in which a multiple gene analysis is required such as for the personal identification. PMID- 11218757 TI - [Survey on postmortem examination to police surgeons and emergency physicians. Possibility of physicians' assist in mass-disaster]. AB - We conducted a questionnaire survey of police surgeons and emergency physicians, inquiring about their experience of medicolegal investigation of death and their willingness to join a death investigation team in a major disaster. The questionnaire also asked about their knowledge about and interest in the forensic specialist system established by the Japanese Society of Legal Medicine. Police surgeons were generally willing to join an investigation team only if a disaster occurred in or close to their hometown, because they could not afford more than several days away from patient care. Although many of the emergency physicians were willing to join a death investigation team, they had difficulty in doing so without permission or orders from their employer or the authorities concerned. The survey found that the percentage of aged police surgeons was increasing among those surveyed. This fact, in combination with the current emphasis of postgraduate education on specialty training, threatens to cause a substantial lack of physicians available for medicolegal investigation of death. Therefore, it is urgently necessary to establish a system of training resident and emergency physicians in medicolegal investigation of death. In addition to providing postgraduate training in medicolegal investigation of death to prospective trainees who are emergency physicians at major hospitals in potential disaster stricken areas, the medical school should incorporate forensic medicine in postgraduate training programs so that they can actively perform death investigation on disaster victims dying before or after arrival at their hospitals. Furthermore, the forensic community should make every effort to increase the number of autopsies in each department of forensic medicine and to expand the medical examiner system throughout Japan that is currently in practice only in the Metropolis of Tokyo and Yokohama, Nagoya, Osaka and Kobe Cities in order to incorporate forensic training in the postgraduate clinical training programs that will become compulsory in 2004. PMID- 11218758 TI - [Effects of the expression of the expert opinion on prosecution]. AB - We carried out a questionnaire survey on judicial apprentices with a case died of subarachnoid hemorrhage to examine whether the expression of the text and supplementary explanation of the expert opinion affect judicial decisions and findings of facts. The survey results suggest that both the expressions of the text and the supplementary explanation may have an effect on the decision. That is, judicial apprentices who read the text expressed that "it was not clear whether the subarachnoid hemorrhage was traumatic or not" with the explanation are less likely to indict for injury resulting in death than those who read the text expressed that "it was not contradictory that the subarachnoid hemorrhage was traumatic" without the explanation. Additionally, we found that these two factors affected the reader's findings of fact. Particularly, the text expressed that "it was not contradictory" without a supplementary explanation is prone to give a conclusive conviction to readers. These results suggest that how a medical diagnosis would be legally interpreted in court depend to some extent upon the expression and the supplementary explanation of the expert opinion. The text of an expert opinion should be expressed to report the medical diagnosis exactly. When autopsy cannot determine the definitive cause of the death, detailed explanation should be supplemented lest the expert opinion give a conclusive conviction. Moreover, we suggest that it is necessary to standardize the form and expression of the expert opinion hereafter. PMID- 11218759 TI - [mRNA detection of beta-myosin heavy chain gene in the autopsy cases of hypertrophic cardiomyopathy]. AB - A known trigger of sudden cardiac death, hypertrophic cardiomyopathy (HCM) is associated with a point mutation in or overexpression of MYH7, which encodes the sarcomere protein beta-myosin heavy chain. We used nested RT-PCR to detect MYH7 mRNA in left ventricular myocardial tissue. We extracted total RNA from tissue samples that had been obtained after autopsy of 8 people who had died from HCM related sudden death and that had been fixed in 10% formalin solution for as long as 4 years. The abundance of total RNA extracted from the 100 mg samples of cardiac muscle ranged from 10 to 24 mg/ml. The products of the nested RT-PCR were electrophoresed on a denaturing 8% polyacrylamide gel, and the MYH7 mRNA product was detected as a 424 bp band. MYH7 mRNA was easier to detect in tissue that had been fixed for shorter rather than longer periods. In addition, the greater the cardiac weight, the higher was the yield of the MYH7 mRNA product. Although mRNA had been detected by using RT-PCR on formalin-fixed paraffin-embedded tissue, no one previously had identified by using RT-PCR or nested RT-PCR on formalin-fixed tissue. By using nested RT-PCR, we were able to detect MYH7 mRNA in myocardial tissue that had been fixed in formalin solution for 4 years. Our results are applicable to retrospective examination into the cause of death in cases of sudden cardiac failure. PMID- 11218760 TI - [Creating language model of the forensic medicine domain for developing a autopsy recording system by automatic speech recognition]. AB - For the purpose of practical use of speech recognition technology for recording of forensic autopsy, a language model of the speech recording system, specialized for the forensic autopsy, was developed. The language model for the forensic autopsy by applying 3-gram model was created, and an acoustic model for Japanese speech recognition by Hidden Markov Model in addition to the above were utilized to customize the speech recognition engine for forensic autopsy. A forensic vocabulary set of over 10,000 words was compiled and some 300,000 sentence patterns were made to create the forensic language model, then properly mixing with a general language model to attain high exactitude. When tried by dictating autopsy findings, this speech recognition system was proved to be about 95% of recognition rate that seems to have reached to the practical usability in view of speech recognition software, though there remains rooms for improving its hardware and application-layer software. PMID- 11218761 TI - [Detection of methamphetamine in a severely burned cadaver--a case report]. AB - We report an autopsy case of a severely burned cadaver in which methamphetamine (MA) and amphetamine (A) were detected. A severely burned cadaver was found in a burned-out car on the seashore. At the autopsy, the drug screening test in the urine using Triage system gave positive result for MA and/or A. Qualitative analysis by gas chromatography/mass spectrometry (GC/MS) confirmed the presence of MA and A. The concentrations of MA and A (mumol/100 g) were 1.66 in the thermo coagulated blood, 16.3 in the urine, 4.60 in the cerebrum, 4.11 in the lung, 7.84 in the liver, 0.94 in the skeletal muscle and 0.54 in the bone marrow. From these results, we concluded that the man had been under the moderate MA and A intoxication. The cause of death was diagnosed as the death of fire on the basis of autopsy findings, and the cadaver was identified as the owner of the car by the DNA typing. This case indicated the importance of drug screening tests in autopsy cases. Furthermore, the qualitative and quantitative analysis of MA and A should be successfully performed by GC/MS even in the case of severely burned cadaver. PMID- 11218762 TI - [Restoration of motor function by functional electrical stimulation]. PMID- 11218764 TI - [Transsphenoidal surgery assisted by navigation system]. AB - Microneurosurgical technique combined with precise localization of lesions, can minimize the invasiveness of neurosurgical procedures. This report describes the usefulness of the neuronavigation system in transsphenoidal surgery. Nineteen transsphenoidal operations for sellar lesions including pituitary adenoma, clival chordoma, Rathke's cleft cyst and suprasellar germinoma were assisted by the optical tracking system (OTS). Operations were performed either through the sublabial or the endonasal approach using an operative microscope and, to a certain extent, the endoscope. All five microadenomas were totally removed. The tumors could be precisely localized by the navigation system. Four out of seven macroadenomas were totally removed. The operations were assisted effectively by the excellent guidance to the lateral margin of the tumors and the internal carotid arteries provided by the navigation system. The endonasal approach, in which the surgeon looks through a nostril at the sellar floor obliquely, was especially facilitated by the three-dimensional view provided by the system. The navigation system, however, was not useful in estimating the amount of the suprasellar residual tumor because of the dislocation that occurred during the tumor removal. PMID- 11218763 TI - [Continuous intrathecal administration of nicardipine using a portable infusion pump system for management of vasospasm after subarachnoid hemorrhage]. AB - We studied the feasibility of intrathecal nicardipine administration using a portable infusion pump system in five cases (two males and three females) of subarachnoid hemorrhage (SAH). All of the five cases manifested severe SAH of Hunt & Kosnic grade 3 or 4, and Fisher CT group 3. Aneurysmal sites of five cases were as follows: three internal carotid-posterior communicating artery (IC-PC) aneurysms and two anterior communicating artery (Acom) aneurysms. The container of the infusion pump system was filled with 105 ml of nicardipine-saline solution (2:1), and this system was connected to the cisternal tube. The solution was continuously injected at a daily dose of 12 ml (8 mg of nicardipine). This therapy was continued for 14 days, and new nicardipine solution was supplied only once at 8 days after the operation during this therapy. No postural restraint of patients was necessary, even during physical movement for rehabilitation. Postoperative angiography was performed in three of five cases at one week after the operation. No angiographic vasospasm was observed in any of the three cases. Symptomatic vasospasm was observed in one case of right IC-PC aneurysm as a transient total aphasia and right hemiplegia, which recovered within several hours due to induced hypervolemia and hypertension therapy. Mild meningitis at 14 days after the operation complicated this treatment in one case, but it improved in a few days after the cisternal tube was removed. It was speculated that meningitis was caused by cerebrospinal fluid leakage from the scalp exit site of the cisternal tube. All of the five cases had obtained good recovery at three months after the operation. These results show that, although this method involves a risk of infection, it has the advantage of easiness and convenience over conventional methods. Though further improvement of this method is required, this preliminary stage is potentially useful for delivering not only nicardipine, but also for other drugs which may be used in intrathecal administration therapy. PMID- 11218765 TI - [Relationship of postoperative residual air and recurrence in chronic subdural hematoma]. AB - The possibility exists that residual air after surgery is one cause of recurrence of chronic subdural hematoma. We have devised a new simple method which decreases postoperative residual air, using external drainage and an endoscope. First, we make endoscopic observations of the inner aspect of the hematoma cavity. Then, we insert external drainage apparatus into the most frontal area of the hematoma cavity, we regard this location as the most appropriate place to ensure most effective drainage. The present study included 37 chronic subdural hematomas in 32 patients who had been treated between January and December, 1999. Their ages ranged from 48 to 86 years old, with an average of 72 years. Insertion of external drainage in the most frontal area of the hematoma cavity was successfully achieved in 27 (73%, Group I) out of 37 cases and resulted in no recurrence. In the remaining 10 hematomas (27%, Group II), external drainage was not able to be inserted in the most frontal area, and four hematomas (40%) had recurrence (p < 0.01 vs Group I). Insertion in the most frontal area of the hematoma cavity decreases residual air after surgery, and may be effective for the prevention of recurrence of chronic subdural hematoma. PMID- 11218766 TI - [Preliminary results of PET activation study in cerebral arteriovenous malformation (AVM), using C15O2 and 18F-FDG]. AB - The authors applied PET activation study to two patients with arteriovenous malformation (AVM) to localize primary motor cortex before surgery or embolization. The change in regional cerebral blood flow (rCBF) was measured during foot movements in Case 1 who had a 2-cm AVM located in the post-central gyrus. Superimposed PET/MRI images revealed that the rCBF increase was located in the pre-central gyrus. Its validity was confirmed by intraoperative cortical mapping using electrical median nerve stimulation. The patient safely underwent total removal of AVM. The change in regional cerebral metabolic rate for glucose (rCMRglc) was measured during hand movements in Case 2 who had a huge AVM over the central sulcus. Superimposed PET/MRI images revealed that hand movements significantly increased rCMRglc in the frontal cortex, which was separated from the original primary motor area. The patient safely underwent partial embolization, although he suffered transient weakness of the face after embolization. The preliminary results strongly suggest that PET activation study is useful to localize precisely cortical functions of the patients with AVM, thus reducing morbidity after treatment. The results also suggest that cortical functions may undergo translocation when huge AVM involves the eloquent area. PMID- 11218767 TI - [A case of the spinal subdural hematoma formation following ventriculoperitoneal shunting for von Recklinghausen's disease associated with aqueductal stenosis]. AB - Von Recklinghausen's disease associated with hydrocephalus due to non-tumoral aqueductal stenosis is rare. Furthermore the formation of subdural hematoma within the spinal canal is also a very rare complication of ventriculoperitoneal shunt. We presented a case of spinal subdural hematoma formation following ventriculoperitoneal shunting for von Recklinghausen's disease associated with aqueductal stenosis. A 10-year-old girl with von Recklinghausen's disease was referred to our hospital for gait disturbance during the previous 8 months. Magnetic resonance imaging (MRI) revealed hydrocephalus due to non-tumoral aqueductal stenosis, and ventriculoperitoneal shunt was instituted. Three months later, the patient developed lumbar pain and paraplegia. MRI revealed subdural hematoma in the lumbosacral spinal canal, and bilateral intracranial subdural hematoma were shown on computerized tomography (CT) scans. Subdural hematoma in the lumbosacral spinal canal was evacuated by laminectomy. Improvement of her neurological deficit was obtained postoperatively, and intracranial subdural hematomas disappeared spontaneously. Spinal subdural hematoma is assumed to be formed by the migratory movement of intracranial subdural hematoma under the influence of gravity. A characteristic finding of MRI is that such a subdural hematoma in the lumbosacral canal is located around the cauda equina. PMID- 11218769 TI - [Simultaneous carotid and coronary artery surgery in asymptomatic carotid artery stenosis--report of three cases]. AB - Some patients with coronary artery disease are diagnosed as having additional carotid artery disease. This subset of patients has been identified as a high risk group for cardiac and cerebral complications following surgical intervention. Three patients who underwent combined CEA/CABG for coexistent asymptomatic carotid occlusive disease are reported. Case 1: A 69-year-old female who suffered chest pain on exertion. Her coronary angiogram showed severe stenosis of three vessels. Her carotid angiogram showed 98% stenosis of the right internal carotid artery and poor collateral circulation. The severe stenosis of her carotid artery was considered as a risk factor for perioperative cerebral stroke. Intraoperatively, CEA preceded the CABG. Postoperative course was uneventful. Case 2: A 64-year-old male. Intermittent claudication was his initial symptom. His coronary angiogram showed stenosis in three vessels and carotid angiogram showed 75% stenosis in the right carotid artery. Simultaneous CABG and CEA was performed. His postoperative course was uneventful. Case 3: A 62-year-old male whose ECG indicated ischemic heart disease, although he had no symptoms. His coronary angiogram showed stenosis in three vessels, and 80% stenosis of his right carotid artery was observed by carotid angiogram. He underwent simultaneous surgery, and had an uneventful postoperative course. It has been reported that 1.5-8.7% of CABG patients have severe carotid artery stenosis, and perioperative cerebral stroke occurs in 0.9-16%. Simultaneous surgery was successful in our three patients who had asymptomatic carotid artery stenosis. Using this surgical approach for critical coexistent disease may minimize the incidence of perioperative cerebrovascular complications in patients undergoing CABG. PMID- 11218768 TI - [Systemic non-Hodgkin lymphoma initially presented with visual disturbance due to intrasellar lymphoma--a case report]. AB - A case with systemic non-Hodgkin lymphoma involving the sella turcica and kidney is reported. A 69-year-old man presented with a progressive two month history of visual disturbance and headache. Neurological examination revealed bilateral visual disturbance and right optic atrophy. MRI showed a contrast-enhancing mass in the sella turcica. The tumor extended to the right optic nerve. Without extensive studies for systemic disease, the patient immediately underwent transsphenoidal surgery. The slightly firm, fibrous and vascular-rich tumor was subtotally removed. The histopathological examination revealed a malignant lymphoma, diffuse-large-cell type with B-cell phenotype. The postoperative course was uneventful and the patient's symptoms subsided gradually. The patient received radiation therapy and the tumor disappeared. Postoperative CT examinations of the abdomen and pelvis revealed a large mass at the upper portion of the left kidney. Ga-scan also suggested the mass to be consistent with the abdominal CT. However, the patient suddenly died of acute heart failure with unknown cause just before starting chemotherapy for systemic lymphoma. Patients presenting primary central nervous system lymphoma (PCNSL) may have systemic non Hodgkin lymphoma. To exclude systemic non-Hodgkin lymphoma, systemic investigation is essential for the initial management of patients presenting PCNSL. PMID- 11218770 TI - [Serial angiographical changes of a ruptured dissecting vertebral aneurysm]. AB - A 54-year-old woman presented a subarachnoid hemorrhage from a ruptured dissecting aneurysm on the right vertebral artery. A right vertebral angiogram revealed a fusiform dilatation distal to the right posterior inferior cerebellar artery and "pseudo lumen" was observed in a delayed arterial phase. Conservative treatment was carried out, and the patient condition gradually improved. An angiographical examination for planned endovascular treatment 46 days after the onset, revealed the normalization of the formerly dilated caliber of the right vertebral artery with only a minor luminal irregularity. However, 83 days after the onset, right vertebral angiogram showed reappearance of the fusiform dilatation. The right vertebral angiogram obtained 204 days after the onset showed that the dilated segment of the dissecting aneurysm had become normalized to a slight degree. The serial angiographical changes of the dissecting site might have been due to regression and organization following transient thrombosis of intramural hematoma. Such drastic changes within a short period have not been reported yet. In conclusion, careful repeated follow-up is recommended in monitoring aneurysmal formation during the early to chronic phase after rupture of a dissecting aneurysm. The repetition of angiography is important, because later, if angiography has been performed only once, aneurysmal dilatation may be overlooked. One has to be aware of such changes, because such changes may alter the clinician's decision about treatment, as they did in our case. PMID- 11218771 TI - [Brain stem hemorrhage associated with venous angioma: report of two cases]. AB - The incidence of hemorrhage associated with venous angioma has been considered to be rare. We here report two cases of brain stem venous angioma which also showed brain stem hemorrhage. Case 1; a 15-year-old female had experienced weakness in the left upper extremity 8 months prior to admission. She developed dysfunction of the left cranial nerves, and magnetic resonance imaging (MRI) showed a huge enlarging hematoma in the pons. Cerebral angiography showed venous angioma penetrating through the pons. Evacuation of the hematoma was performed through the fourth ventricle and many small vessels were found in the hematoma. Although all symptoms were partially resolved after the operation, a re-hemorrhage occurred 1 month after the operation. Case 2; a 50-year-old man had suddenly developed headache and vertigo several days prior to admission. Computed tomography (CT) and MRI showed a small hematoma in the lesion with venous angioma adjacent to the hematoma. All symptoms gradually resolved with conservative therapy. PMID- 11218772 TI - [A case of recurrent convexity meningioma with malignant transformation 26 years after total tumor removal]. AB - Meningiomas are common intracranial tumors, the majority of which are considered benign. However, they sometimes show altered biologic behavior, associated with local aggressiveness and late distant metastasis. We report a patient with a convexity meningioma, which recurred as a malignant transformation 26 years after a total tumor removal. A 75-year-old man was transferred to a local hospital because of general convulsions and left hemiparesis. The patient had had an operation for the total removal of a right frontal convexity meningioma at the age of 46 and had been free of its effects until the age of 72. Brain magnetic resonance imaging (MRI) showed a recurrent tumor located in the anterior area of the previous craniotomy. Over the following two and a half years, MRI revealed rapid enlargement and infiltration of the tumor into the brain parenchyma. The primary tumor was nodular, macroscopically well demarcated from the surrounding brain tissue and, histologically, was a transitional type of meningioma without any atypical features. In contrast, the recurrent tumor, whose border was ill defined, had invaded the neighboring brain. A histological specimen of the recurrent tumor showed highly malignant features such as necrosis, intracerebral infiltration, dense cellularity, and high proliferating activity as demonstrated by a cell kinetic study using the MIB 1 staining index. We should be mindful that recurrence from common benign type meningiomas may occur as malignant transformations after more than two decades. PMID- 11218773 TI - [Why do you express the artery as carotid and the vein as juglar though they are all the same neck vessels?]. PMID- 11218774 TI - [Fewer complications--earlier discharge--shorter convalescence]. PMID- 11218775 TI - [Legionella infections: diagnostic and therapeutic challenges]. PMID- 11218776 TI - [Accelerated surgical stay programs. A professional and administrative challenge]. AB - Accelerated surgical stay programs represent a multi-modal, multi-disciplinary concept to reduce postoperative morbidity, hospitalisation and convalescence based upon recent advantages in surgical pathophysiology and pain treatment. Preliminary data from a variety of surgical procedures suggest major improvements in quality of surgical care and cost reduction and call for further controlled or large-size multi-center studies. PMID- 11218777 TI - [Trends in dietary habits in Denmark and Sweden since the 1960s]. AB - Dietary habits in Denmark and Sweden are compared during the period 1965-1998 based on data from Food Balance Sheets. Common trends are an increase in consumption of vegetables, fruits, berries and meat and a decrease in consumption of fats. In the latest ten years percentage of energy from fat has also decreased. Denmark has a higher consumption of fats and meat and a lower consumption of fruits, berries and fish. These differences contribute to a higher percentage of energy from fat in the Danish diet compared to the Swedish. Data consequently indicate that dietary habits in Sweden are healthier than in Denmark. Differences in dietary habits may have contributed to differences in life expectancy between the countries. Disparities in dietary habits are seen in both countries. The tendency is greater social differences in Denmark. PMID- 11218778 TI - [Cancer and prevention]. AB - INTRODUCTION: The aim of the study was to estimate the preventable potential of various types of cancer in Denmark on the basis of present knowledge. MATERIAL AND METHODS: The well-documented factors in lifestyle and environment causing cancer in Denmark were identified from the IARC Monograph series. The population attributable risk per cent (PAR%) and the annual number of preventable cancers were calculated for each aetiology and cancer type around the year 2000. RESULTS: A large proportion of the cancers occurring in the lungs, larynx, upper digestive tract, skin, lower urinary tract, and the uterine cervix is potentially avoidable, whereas only a small proportion of breast and colorectal cancers is preventable on the given knowledge. The main causative factors include active and passive smoking, alcohol intake, exposure to asbestos and other occupational carcinogens, solar and ionising radiation, obesity, human papillomavirus infection in the female genital tract, and infection with Helicobacter pylori. More than 5000 cancers in men and almost 3500 in women annually in Denmark could have been avoided by eliminating exposure to these known carcinogens. This is equivalent to 39% and 23% of all cancers occurring respectively in men and women, around the year 2000. Smoking habits account for more than half of these avoidable cases. DISCUSSION: The incidence of cancer could be greatly reduced through primary prevention, especially of tobacco smoking, which is the major single factor. A large proportion of the cancers occurring in the lungs, larynx, upper digestive tract, skin, lower urinary tract, and the uterine cervix are potentially avoidable. More research in the field of aetiological factors causing female breast cancer and colorectal cancer is much needed in order to be able to prevent these types of cancer. PMID- 11218779 TI - [Cancer treatment in Skane and in Sjaelland. Do differences concerning examination and treatment explain reduced survival among Danish cancer patients?]. AB - INTRODUCTION: Danish cancer patients generally have a poorer survival than Swedish cancer patients. The difference is most pronounced for certain tumour types, e.g. common types such as lung, breast, colorectal, and prostate cancer. The reasons are not clear. The present article examines if differences in the diagnostic workup and treatment can explain some of this variation. MATERIAL AND METHODS: Aspects of the diagnostic workup and treatment of the above mentioned four cancer types are examined using data from cancer registry analyses and official reports. These data are seen in the context of counts of trained personnel and equipment in cancer diagnostics and treatment in the two countries. RESULTS: With regard to lung and breast cancer, the data seem to indicate that Danish patients are diagnosed later, and that Denmark lags behind in treatment capacity. With regard to rectal cancer, the data seem to indicate that concentrating operations in fewer hospitals, and improvements in operation technique have been introduced earlier in Sweden than in Denmark. With regard to prostate cancer, however, the data seem to indicate that many more indolent cases that do not need treatment are diagnosed in Sweden than in Denmark. The total capacity for oncologic treatment, both in terms of trained personnel and equipment, seen in relation to the size of the population, is considerably larger in Southern Sweden than in Eastern Denmark. DISCUSSION: The data for some of the common cancer types seem to indicate that problems in the areas of sufficient capacity for diagnostic workup and treatment may explain some of the difference in survival between Danish and Swedish cancer patients. PMID- 11218780 TI - [An unusual complex of debut symptoms in Wegener's granulomatosis]. AB - We report an unusual case of Wegener's granulomatosis in a patient presenting with stridor and tracheal narrowing as the initial manifestation of the disease. PMID- 11218781 TI - [Deadly indoor climate]. PMID- 11218782 TI - [Do more women lose their breast after screening?]. PMID- 11218783 TI - [Colorectal cancer]. PMID- 11218784 TI - [Long-term results after cemented total hip alloplasty in the treatment of primary hip arthrosis]. PMID- 11218785 TI - [Cigarettes are and remain the great killer]. PMID- 11218786 TI - [Five outbreaks of human ascariasis caused by pig ascaris?]. PMID- 11218787 TI - [Gabapentin--yet another antiepileptic agent for the treatment of neuropathic pain?]. AB - Gabapentin is a recently introduced anti-epileptic drug used as an adjuvant in partial and secondarily generalised tonic-clonic seizures. Its mechanism of action has not been fully elucidated, but it seems that gabapentin may regulate voltage-dependent calcium channels, presumably on a spinal level, in the nociceptive system. Two large, controlled clinical trials of painful diabetic neuropathy and postherpetic neuralgia have demonstrated its analgesic efficacy. The adverse effects associated with gabapentin treatment are relatively harmless, mild to moderate in severity, and usually transient, with tolerance developing 2 3 weeks after start of treatment. Gabapentin and tricyclic antidepressants are efficacious in the treatment of painful diabetic neuropathy and postherpetic neuralgia. PMID- 11218788 TI - [Tramadol and oxazepam. Effect on pulmonry function in elderly patients with chronic obstructive lung disease]. AB - Many patients with chronic obstructive pulmonary disease (COPD) suffer from osteoporotic pain as a result of glucocorticoid treatment and nervous symptoms partly related to their lung disease. There seems to be som reluctance to treat these patients with an opioid or benzodiazepine. Upon request, the Drug Information Centre in Odense made an extensive literature search on the subject. No documentation was found that tramadol additionally depresses the respiration in patients with COPD, nor has oxazepam in clinically relevant doses been found to exacerbate their lung disease. The clinical effect is subject to large interindividual variability, and the use of these drugs should, to a greater extent, rest on experience with the individual patient. There seems to be no reason to maintain a priori this rigoristic reluctance to use tramadol and/or oxazepam in patients with COPD. PMID- 11218789 TI - [Tirofiban (Aggrastat). A non-peptide glycoprotein IIb/IIIa receptor inhibitor]. AB - Platelet aggregation and thrombus formation on a ruptured atherosclerotic plaque plays an important role in the pathogenesis of acute coronary syndromes. Activation of glycoprotein IIb/IIIa receptors (GP-receptors) on the surface of platelets is the final common pathway which leads to the binding of fibrinogen and crosslinking of platelets to form the white thrombus. Antiplatelet therapy reduces the risk of ischaemic complications in patients with acute coronary syndromes. Recently, the GP-receptor antagonists have been introduced. They inhibit the binding of fibrinogen to the GP-receptors and thus prevent platelet aggregation. Tirofiban is a low molecular, intravenously administered GP-receptor antagonist, which in combination with unfractionated heparin in several controlled studies has been shown to decrease morbidity and mortality in patients with unstable angina pectoris and non-Q-wave infarction and, in patients subsequently undergoing percutaneous coronary intervention. PMID- 11218790 TI - [Therapeutic, activated charcoal to pediatric poisoning patients]. PMID- 11218791 TI - [Eptifibatide (Integrilin)]. AB - Eptifibatide (Integrilin) is a specific blocker of the glycoprotein IIb/IIIa receptor and an effective inhibitor of platelet aggregation. It reduces coronary events in patients with acute coronary syndromes and no elevation in the electrocardiographic ST segment. The present summary discusses the indications for the use of eptifibatide/Integrilin based on recent clinical trials and cost benefit analyses. PMID- 11218792 TI - [Abciximab (ReoPro) in the treatment of acute coronary syndromes]. AB - Platelet activation plays a major role in the pathophysiology of acute coronary syndromes (ACS). Inhibition of platelet function is the basic pharmacological treatment of ACS. Platelet membrane glycoprotein IIb/IIIa inhibitors, a new class of potent antiplatelet agents, have been used in the treatment of ACS and in the prevention of complications after percutaneous coronary interventions (PCI). Several large clinical trials have demonstrated the effectiveness of this class of agents. The first of these agents to show beneficial effects after coronary interventions was the mouse/human chimeric Fab fragment antibody c7E3 abciximab (ReoPro). The purpose of this article is to describe the pharmacology of abciximab and to review the results of the clinical trials carried out with the drug in patients with ACS, treated either with or without acute/elective PCI. PMID- 11218793 TI - [Diagnosis. Pneumocystis carinii]. PMID- 11218794 TI - The elections and health care: an opportunity for bipartisan progress? PMID- 11218796 TI - Learning from the pros. Health plans go to customer satisfaction school. PMID- 11218795 TI - A day in the life of managed care. Blue Cross and Blue Shield of Georgia's Jay Kulkin, MD. PMID- 11218797 TI - Putting members first is top initiative at Blue Cross and Blue Shield of Massachusetts. PMID- 11218798 TI - Exporting American-style managed care: what works and what doesn't. PMID- 11218799 TI - Communicating from the brink. PMID- 11218800 TI - Health plans take steps to implement new federal standards for electronic transactions. PMID- 11218802 TI - Reducing tobacco use: health plans take an active role. PMID- 11218801 TI - Major HIPAA compliance efforts underway, despite uncertainty. PMID- 11218803 TI - Getting physicians online. PMID- 11218804 TI - By the numbers. Poll finds voters prefer external review to lawsuits. PMID- 11218806 TI - Correlation and modulation of Ehrlich ascites tumor growth with tumor-plasma IgA. AB - Plasma IgA level of Ehrlich ascites tumor bearing mice showed correlation with progress of tumor growth. In PAGE analysis total plasma IgA separated into 3 major bands corresponding to mol. wt. > or = 669,000 daltons, identical to 443,000 daltons and between 443,000 and 150,000 daltons. All the three bands increased gradually with progress of tumor growth upto day 14 and then declined on day 16. Total plasma IgA isolated by anti-IgA affinity chromatography when adoptively transferred to mice inhibited tumor growth. Affinity-purified plasma IgA separated into three major peak fractions after Sephadex G-200 column chromatography which corresponded with the bands of IgA on PAGE analysis. Three Sephadex G-200 IgA fractions when adoptively transferred to tumor-bearing mice showed effect different from total IgA. High mol. wt. IgA fraction (> or = 669,000 daltons) inhibited tumor growth whereas medium mol. wt. fraction (identical to 443,000 daltons) enhanced tumor growth. The low mol. wt. IgA fraction (< 443,000 and > 150,000 daltons) had no significant effect on tumor growth. The high mol. wt. IgA fraction enhanced tumor killing ability of peripheral blood lymphocytes (PBL) and peritoneal macrophages of tumor bearer in vitro. Medium mol. wt. IgA fraction inhibited tumor-killing ability of PBL in vitro but had no significant effect on peritoneal macrophages. The low mol. wt. IgA fraction showed a mild enhancing effect on tumor-killing ability of PBL but had no significant effect on peritoneal macrophages. The results established importance of IgA in tumor growth regulation and its therapeutic potentiality. The results indicated that tumor growth modulation by tumor plasma IgA is also mediated by its effect on cellular anti-tumor immune factors of the host. PMID- 11218805 TI - Immunology of gangliosides. AB - This review discusses the immunology of gangliosides from the perspective of tumor, neuronal and general immunology. Antiganglioside antibodies in human sera are invariably IgM and are found in healthy individuals. Their titers decline with age. Persistent high titer of IgM is associated with several diseases, particularly neuropathies. Membrane-bound gangliosides are important tumor associated antigens and targets for immune attack. Cells enriched with gangliosides can be used as cancer vaccines. Efficacy of these vaccines depends on the viability of whole cells, integrity of the cell membranes, adjuvants and topography of the tumor-associated antigens. The role of antiganglioside IgM is to eliminate the immunosuppressive gangliosides shed from tissues during ageing, degeneration of neural and extraneural tissues, and tumor growth and necrosis. In addition, in vitro observations with human and murine monoclonal antibodies suggest that they are capable of complement dependent cytotoxicity and apoptosis. PMID- 11218807 TI - Effect of feeding protein deficient diet on phospholipid turnover and protein kinase C mediated protein phosphorylation in rat brain. AB - Feeding of protein deficient diet is known to alter the transmembrane signalling in brain of rat by reducing total protein kinase C (PKC) activity. Phospholipid metabolism regulates the activation of PKC through generation of second messengers and the extent of PKC activation accordingly influences the magnitude of phosphorylation of its endogenous substrate proteins. Thus it was speculated that ingestion of protein deficient diet may modify the turnover rate of membrane phospholipids and magnitude of phosphorylation of endogenous substrate proteins of PKC. The experiments were conducted on rats fed on three different types of laboratory prepared diets viz. casein (20% casein), deficient (4% protein, rice flour as source of protein) and supplemented (deficient diet supplemented with L lysine and DL-threonine) for 28 days. The metabolism of phosphoinositides (PIs) and phosphatidyl choline (PC) was studied by equilibrium labeling with [3H] myo inositol and [14C methyl] choline chloride respectively. The phosphorylation of endogenous substrate proteins of PKC was studied by using 32P-gamma-ATP followed by SDS-PAGE and autoradiography. The results suggest that in deficient group, there is an increased incorporation of [3H] myo inositol in PIs and inositol phosphate pool in comparison to the casein group. The phosphatidyl inositol (PI) turnover reduced, although there was a marginal increase in the phosphatidyl inositol monophosphate (PIP) and phosphatidyl inositol bis phosphate (PIP2). Supplementation of diet showed a reversal of the pattern towards control to a considerable extent. In the deficient group, PC metabolism showed an increased incorporation of [14C methyl] choline in choline phospholipids but decreased incorporation in phosphoryl choline in comparison with the casein group. The increase in total PC contents was significant but marginal in residue contents. The turnover rate of PC increased only marginally and that of residue declined. Supplementation of diet reduced the total contents of PC and residue, but the turnover rate of PC and residue remained still higher. Phosphorylation of endogenous proteins showed four different proteins of 78, 46, 33 and 16 kDa to be the substrates of PKC in casein group. In deficient group, phosphorylation of these proteins increased markedly while supplementation of diet had a reversing effect rendering the values to be intermediate between casein and the supplemented group. The changes in phospholipid metabolism and in phosphorylation of endogenous substrate proteins of PKC suggest that dietary protein deficiency causes alterations in transmembrane signalling mechanism in rat brain. These effects are partially reversed by improving the quality of proteins in the diet. PMID- 11218808 TI - Studies on anticonvulsant actions of L-deprenyl. AB - L-Deprenyl (Selegeline) introduced for use in parkinson's disease, is implicated to show beneficial effects in epilepsy, alzheimer's disease, cognition, depression and other age related neurological diseases. In this study, we investigated the CNS effects of L-deprenyl with special reference to epilepsy, anxiety and cognition and memory in mice. L-deprenyl (10, 20 and 40 mg/kg) showed a significant anticonvulsant activity against pentylenetetrazole (PTZ)-induced convulsions. Combination of L-deprenyl (10 mg/kg) with the sub-protective dose of diazepam (1 mg/kg) showed potentiation of the anticonvulsant effect. In the maximal-electroshock (MES)-induced convulsions, L-deprenyl (10 mg/kg) significantly delayed the onset and decreased the duration of extensor phase. Its combination with the lower dose of phenytoin (10 mg/kg) showed potentiation in response compared to the per se effect of both the drugs. However, L-deprenyl did not show any protective effect in lithium-pilocarpine induced status epilepticus. Acute treatment with L-deprenyl had no effect on learning and memory. In chronic treatment, L-deprenyl per se showed no effect on learning and memory but did improve the condition in mice with scopolamine induced memory deficit. L-Deprenyl per se was anxiogenic though in combination with diazepam (1 mg/kg) it potentiated the antianxiety effect of the latter. The above observations suggest that in epilepsy, L-deprenyl might be acting partially by influencing the GABAA/benzodiazepine mechanism in the brain (similar to diazepam and phenytoin), and in cognition enhancing effect, the cholinergic system might be playing a role. Thus, L-deprenyl could prove to be an adjuvant in the antiepileptic therapy and beneficial in dementia associated with epilepsy. PMID- 11218809 TI - Pre-clinical toxicity evaluation of leaf-stalk extractive of Piper betle Linn. in rodents. AB - Studies on pre-clinical toxicity were undertaken to determine the haematological and biochemical changes after administration of alcoholic extract of leaf-stalk of P. betle in rats and mice. Acute and chronic toxicity experiments were performed on mice and rats according to WHO protocol. Different doses of plant extractive were administered for toxicity studies on short and long term basis. Haematological, biochemical profiles and enzymatic studies (transaminases and phosphatases) indicated that the drug (plant extractive) was devoid of toxicity. PMID- 11218810 TI - Anxiolytic activity of Indian Abies pindrow Royle leaves in rodents: an experimental study. AB - Putative anxiolytic activity of ethanolic extract of Indian A. pindrow Royle leaf was investigated in rats using various experimental paradigms of anxiety viz. open field exploratory behaviour, elevated plus maze (EPM) and elevated zero maze (EZM) tests. Pilot studies indicated that single dose administration of extract had little to no acute behavioural effects, hence the extract was administered orally at different dose levels once daily for three consecutive days, while lorazepam (LR) (0.5 mg/kg, i.p.) was administered acutely. Ethanolic extract of A. pindrow (AP) leaves (50 and 100 mg/kg, p.o.) showed significant anxiolytic effects on all the paradigms of anxiety. The results indicate that AP and LR induced a significant increase in open field ambulation and slight increase in rearings and activity in center, whereas grooming and faecal droppings remain unchanged. In EPM, significant augmentation of open arm entries, and time spent on open arms was noted in AP treated rats. In EZM test, significant increase in time spent on open arms and entries in open arms was observed, whereas slight increase in head dips and stretched attend postures was also observed. The AP extract showed consistent and significant anxiolytic activity in all the tests. The effects induced by ethanolic extract of AP were less marked than those of lorazepam were. PMID- 11218811 TI - Effect of pentoxifylline on cyclosporine-induced nephrotoxicity in rats. AB - Effect of unique hemorrheologic agent pentoxifylline (PTX) was investigated on cyclosporine (CsA) induced nephrotoxicity in rats. Compared to saline control, CsA produced significant increase in blood urea and serum creatinine. Pentoxifylline treatment prevented the CsA-induced rise in blood urea and serum creatinine. Creatinine clearance (Ccr) and lithium clearance (Licr) was decreased with CsA. PTX treatment prevented the CsA-induced decrease in Ccr and Licr. Malondialdehyde (MDA) was increased with CsA compared to saline treated animals. PTX prevented the CsA-induced MDA rise. Kidney form CsA treated rat showed marked vacuolar degeneration of tubular epithelium with excess of microcalcification. Severity of the lesions was markedly reduced in rats treated with PTX plus CsA. The results indicate that PTX reduces CsA-induced renal toxicity in rats. PMID- 11218812 TI - Efficacy of dietary protein in alleviating toxicity of monocrotophos in rats. AB - Monocrotophos administration at intervals induced variable responses in phosphatases, transaminases and aldolase of liver and plasma. Hepato-toxicity was aggravated under protein deficient state. A weak resistance to toxicity was observed in rats on low protein diet (5%). However, animals fed on protein enriched diet (20%) indicated an elevation in tissue defense mechanism and were able to combat toxic stress of monocrotophos, though partially. A higher protein level may prove efficient and significant for alleviating pesticide toxicity. PMID- 11218813 TI - Salmonella. typhi OMPs induced immunomodulation in peritoneal macrophages. AB - The immunomodulatory properties of outer membrane proteins (OMPs) from S. typhi Ty2 were studied in mouse model at 72 hr and 20 days post-infection. Inspite of reduction in the number of macrophages and their protein content observed in the immunized group vis-a-vis infected group, OMPs activated macrophages showed significant upregulation of NO. At 20 days post infection, the level remained almost the same suggesting the prolonged cytotoxic and cytostatic activity due to the long lasting effects of OMPs activated macrophages. Higher activity of SOD in these aged cells pointed out towards the protective efficacy of OMPs to keep the macrophages themselves away from the noxious effects of O2-. Lower level of acid phosphatase in the macrophages from immunized mice group indicated the involvement of oxygen dependent rather than oxygen independent killing process. The enhanced uptake of organisms and their killing could be related to the production of oxygen and nitrogen radicals in the OMPs immunized group. PMID- 11218814 TI - Isolation and characterisation of legumin promoter sequence from chickpea (Cicer arietinum L.). AB - Seed specific promoters are useful for expression of foreign genes in the seeds. We have isolated a Cicer arietinum legumin promoter from lambda EMBL genomic library and subcloned in pBluescript II KS (-) in Eco RV and Pst I site. The 2.762 kb Hind II Pst I fragment was sequenced completely by dideoxy chain termination method by creating a set of unidirectional deletions of the inserts in pAKKIII. The insert contains mainly upstream sequence (2240 bps) and only a part of structural gene (522 bps) sequence. The 522 bps of the structural gene shows approximately 80% homology with pea legumin A and this is almost the same as chickpea legumin in its sequence. The amino acid sequence derived from the part of the structural gene was similar to the chickpea 5' part of the legumin structural gene with a few variations. A 21 amino acid signal peptide was also deduced like many other legumes. Transcription start site (CAT) was located at 55 bp upstream of the initiation codon ATG. One codon downstream to ATG codon Hind III site was present. TATA box was observed at -30 position, with a consensus of CCTATAAATAACC. The consensus CATGCAAG, a part of legumin box was noticed at -110 bp position. At -295 to -265 bp upstream AGGA box like sequences were observed and a 56 bp perfect repeat was located between -913 bp and -972 bp. Strong homology with pea promoter sequence near the CAT sequence was noticed which gradually decreased towards the upstream region. Thus the cloned fragment contains a full length promoter which can be utilised for expression of foreign genes in seeds of chickpea. PMID- 11218815 TI - Analogue-resistant mutants of Azotobacter chroococcum derepressed for nitrogenase activity and early ammonia excretion having potential as inoculants for cereal crops. AB - Spontaneous mutants resistant to methionine sulfoximine (Msx), methyl alanine (Mal) and methyl ammonium chloride (Mac) were derived from A. chroococcum strain A103. Msx and Mal-resistant mutants expressed 1.73 to 10.98% of the fully derepressed nitrogenase activity when grown in Burk's medium containing ammonium acetate. Mac-resistant mutants did not express nitrogenase activity in ammonium acetate supplemented medium. The mutants excreted ammonia even after 2 days of growth and some mutants excreted more ammonia as compared to the parent. Selected mutants were inoculated on wheat (Triticum aestivum) and barley (Hordeum vulgare) under field conditions. Majority of the derepressed mutants increased grain yield of wheat and barley varying from 1.2 to 33.3%. However, host-dependent effects on grain yield were observed with different mutants. Two mutants, Mal 27 and Mac 19 showed significant increase in grain yields of both the crops. The results suggest that metabolic analogue-resistant mutants of Azotobacter have potential for use as a biofertilizer for cereal crops. PMID- 11218816 TI - Effects of stress and food deprivation on catfish, Heteropneustes fossilis (Bloch). AB - No significant changes in plasma cortisol and plasma osmolarity (the indicators of primary and secondary response respectively) were observed when the blood samples were obtained from unanaesthetized, anaesthetized and stressed catfish, H. fossilis. The results suggest that the catfish is fairly hardy and not easily susceptible to stress by routine laboratory handling. The sustained plasma glucose levels and decreased liver and muscle glycogen concentrations during cessation of feeding of the catfish suggest that during period of food deprivation, it draws its energy through glycogenolysis. Hence, in any study dealing with carbohydrate metabolism, the catfish needs to be fed during acclimation and experimental periods. PMID- 11218817 TI - Influence of culture parameters on paper mill effluent decolourization by a white rot fungus Ganoderma lucidum. AB - Efficacy of a white rot fungus G. lucidum for reduction of colour of paper mill effluent under various growth conditions was evaluated. G. lucidum cultured in IBME medium supported maximum colour reduction on 18th day of fungal growth. The optimization of growth parameters further improved colour reduction. The 18 day old culture at 4 g/l inoculum concentration resulted in maximum decolourization (89%) of the effluent with pH adjusted to 6.5 at 35 degrees C along with maximum reduction in biological oxygen demand and chemical oxygen demand. Relative contribution of lignin peroxidase and laccase to the decolourization of paper mill effluent by G. lucidum was also observed. PMID- 11218818 TI - Effect of naloxone on GnRH-induced LH and FSH release in buffalo, Bubalus bubalis. AB - The effect of naloxone on GnRH-induced LH and FSH release was measured in buffaloes in luteal phase of estrous cycle. Animals were administered intravenously, naloxone/saline (50 mg/injection) every 15 min for 3 hr followed by GnRH (100 micrograms). Peripheral plasma LH and FSH concentrations were measured in blood samples collected at 15 min intervals from 1 hr prior to beginning of naloxone/saline treatment up to 3 hr post GnRH administration and every 30 min for the subsequent 3.5 hr. Between the animals of Group I administered naloxone and those of Group II given saline, GnRH-induced peak LH and FSH concentrations, the total LH and FSH released in response to GnRH, and the time to peak LH and FSH concentrations were not significantly different. The results of the present study suggest the absence of a direct effect of naloxone on pituitary responsiveness to GnRH. PMID- 11218819 TI - Changes of haemolymph protein profile in the larva of Pericallia ricini (Fabricius) parasitised by the Braconid Wasp, Apanteles taragamae Viereck (Hymenoptera: Braconidae). AB - Parasitism by the braconid wasp, A. taragamae caused alterations in the haemolymph polypeptides of woolly bear larvae of P. ricini. Analysis of haemolymph proteins by SDS-PAGE and densitometry showed that the quantities of haemolymph proteins were reduced dramatically in the parasitised larvae. Simultaneously, parasitism induced large amount of 95 kDa polypeptides in the haemolymph of the parasitised larvae. Also, a remarkable induction of 43 and 45 kDa polypeptides which are not detectable in non-parasitised larvae appeared in the parasitised larvae. PMID- 11218820 TI - X-ray microanalysis of elements of VA mycorrhizal and non-mycorrhizal Pennisetum pedicellatum roots. AB - Chemical composition of inter and intracellular hyphae was elucidated in Pennisetum pedicellatum roots colonized by Gigaspora margarita by employing energy dispersive X-ray microanalysis. Maximum amount of phosphate was estimated in polyphosphate granules present in the roots. Amount of phosphate was low in fungal hyphae, arbuscular trunks and degenerated arbuscules. Elements S, K and Ca were present in the hyphae, arbuscular trunk and degenerated arbuscules. PMID- 11218821 TI - Effect of light intensity on in vitro multiple shoot induction and regeneration of cotton (Gossypium hirsutum L. cv Khandawa-2). AB - Cotyledonary nodes taken alongwith shoot apex from seedlings of cotton (G. hirsutum) proliferated into shoots on nutrient agar medium supplemented with cytokinins. In the presence of optimal plant growth regulators, low light intensity enhanced the number of shoots initiated per explant in cotton. An average of 33.5 +/- 2.9 shoots were obtained from a single explant cultured for 8 weeks which is about four fold higher than the values reported in earlier protocols. The isolated shoots were rooted on nutrient agar medium supplemented with alpha-naphthalene acetic acid and transferred to soil after acclimatization. Regenerated plants were morphologically identical to the seed-germinated plants and were fertile. PMID- 11218822 TI - Tolerance of Oscillatoria isolates to agrochemicals and pyrethroid components. AB - Four isolates of Oscillatoria sp from an Indian paddy field have been tested for their tolerance to agrochemicals and pyrethroid components. The isolates possessed considerable tolerance to agrochemicals and reduced toxicity of pyrethroid components towards fish. PMID- 11218823 TI - Size dependent bioaccumulation of heavy metals by Mytilopsis sallei (Recluz) at Visakhapatnam harbour. AB - Relationship between body size and bioaccumulation of copper, zinc, lead and cadmium in the fouling bivalve, M. sallei (Recluz) in Visakhapatnam harbour was studied. While concentration of copper, zinc and lead decrease with increasing size, no such relationship is observed for cadmium. PMID- 11218824 TI - Protective antioxidant effect of vitamins C and E in streptozotocin induced diabetic rats. AB - We have investigated the protective effect of vitamin C and E together supplementation on oxidative stress and antioxidant enzyme activities in the liver of streptozotocin-induced diabetic rats, unsupplemented diabetic and control rats. We also determined the levels of both the vitamins and oxidative stress in plasma. Vitamin supplementation in diabetic rats lowered plasma and liver lipid peroxidation, normalised plasma vitamin C levels and raised vitamin E above normal levels. In liver, the activity of glutathione peroxidase was raised significantly and that of glutathione-S-transferase was normalised by vitamin supplementation in diabetic rats. The levels of lipid peroxidation products in plasma and liver of vitamin-supplemented diabetic rats and activities of antioxidant enzymes in liver suggest that these vitamins reduce lipid peroxidation by quenching free radicals. PMID- 11218825 TI - Motor and electrographic response of refractory experimental status epilepticus in rats and effect of calcium channel blockers. AB - Effects of various calcium channel inhibitors have been studied in lithium pilocarpine model of status epilepticus. Status epilepticus was induced by administration of lithium chloride (3 meq/kg) followed 21 hr later by pilocarpine (30 mg/kg). Diltiazem (5 and 10 mg/kg) was not effective in delaying onset of convulsions. Verapamil (20 mg/kg) showed protection against lithium-pilocarpine induced convulsions. The dihydropyridine nifidepine (2.5 and 5 mg/kg) did not show any protection in this model. Amlodipine (5 and 10 mg/kg) as partially protective. Flunarizine (10 and 20 mg/kg) delayed the onset of forelimb clonus and rearing and only 60% of the rats underwent status in the 20 mg/kg group. Pre treatment of MK-801 led to a potentiation of the antiseizure activity of calcium channel inhibitors. The percent increase in amplitude at various time points with amlodipine pretreatment was significant only at the 30th min recording, and at the rest of the time frames was practically similar as the controls. It can be concluded that the anticonvulsant action of MK-801 can be enhanced by centrally acting calcium channel inhibitors. PMID- 11218826 TI - Prolonged release biodegradable vesicular carriers for rifampicin--formulation and kinetics of release. AB - An attempt has been made to design suitable liposome and niosome-encapsulated drug delivery system for rifampicin and evaluated the same in vitro and in vivo. A modified lipid layer hydration method was employed to prepare these vesicular carriers. The formulated systems were characterized in vitro for size distribution analysis, drug entrapment, drug release profiles and vesicular stability at different conditions of storage. In vivo drug kinetics was evaluated in normal, healthy albino rats for niosomal formulation upon subcutaneous injection and various pharmacokinetic parameters were determined. Niosomes and liposomes exhibited mean diameter of 9.73 and 11.87 microns with entrapment efficiencies of 30.5 and 34.2% respectively. Both the products exhibited sustained release characteristics in vitro with zero order drug release kinetics up to initial 10 hr. Stability evaluation indicated that both formulations were not significantly leaky over a period of one month. Niosomal formulation elevated plasma elimination half life and decreased elimination rate constants for rifampicin in vivo suggested that encapsulation retarded the removal of the drug from circulation compared to free drug due to slow drug release into systemic circulation. A five-fold increase in the area under plasma rifampicin concentration-time curve for niosomal rifampicin as compared to free drug indicated better bioavailability of encapsulated drug. It is evident from this study that niosomes and liposomes could be promising delivery systems for rifampicin with prolonged drug release profiles and reasonably good stability characteristics. PMID- 11218827 TI - Adaptogenic activity of Siotone, a polyherbal formulation of Ayurvedic rasayanas. AB - Siotone (ST) is a herbal formulation comprising of Withania somnifera, Ocimum sanctum, Asparagus racemosus, Tribulus terristris and shilajit, all of which are classified in Ayurveda as rasayanas which are reputed to promote physical and mental health, improve defence mechanisms of the body and enhance longevity. These attributes are similar to the modern concept of adaptogenic agents, which are, known to afford protection of the human physiological system against diverse stressors. The present study was undertaken to investigate the adaptogenic activity of ST against chronic unpredictable, but mild, footshock stress induced perturbations in behaviour (depression), glucose metabolism, suppressed male sexual behaviour, immunosuppression and cognitive dysfunction in CF strain albino rats. Gastric ulceration, adrenal gland and spleen weights, ascorbic acid and corticosterone concentrations of adrenal cortex, and plasma corticosterone levels, were used as the stress indices. Panax ginseng (PG) was used as the standard adaptogenic agent for comparison. Additionally, rat brain levels of tribulin, an endogenous endocoid postulated to be involved in stress, were also assessed in terms of endogenous monoamine oxidase (MAO) A and MAOB inhibitory activity. Chronic unpredictable footshock induced marked gastric ulceration, significant increase in adrenal gland weight and plasma corticosterone levels, with concomitant decreases in spleen weight, and concentrations of adrenal gland ascorbic acid and corticosterone. These effects were attenuated by ST (50 and 100 mg/kg, p.o.) and PG (100 mg/kg, p.o.), administered once daily over a period of 14 days, the period of stress induction. Chronic stress also induced glucose intolerance, suppressed male sexual behaviour, induced behavioural depression (Porsolt's swim despair test and learned helplessness test) and cognitive dysfunction (attenuated retention of learning in active and passive avoidance tests), and immunosuppression (leucocyte migration inhibition and sheep RBC challenged increase in paw oedema in sensitized rats). All these chronic stress induced perturbations were attenuated, dose-dependently by ST (50 and 100 mg/kg, p.o.) and PG (100 mg/kg, p.o.). Chronic stress-induced increase in rat brain tribulin activity was also reversed by these doses of ST and by PG. The results indicate that ST has significant adaptogenic activity, qualitatively comparable to PG, against a variety of behavioural, biochemical and physiological perturbations induced by unpredictable stress, which has been proposed to be a better indicator of clinical stress than acute stress parameters. The likely contribution of the individual constituents of ST in the observed adaptogenic action of the polyherbal formulation, have been discussed. PMID- 11218828 TI - Organogenesis and tissue regeneration of fallopian tube: a desired metaplastic transformation of mesodermal stem cells in live animal models (dogs). AB - The capacity of stem cells of peritonium of mesodermal origin to undergo metaplastic transformation and form different tissues developed from mesoderm germ layer is exploited with ulterior motive to use it in the management of human diseases. The excised fallopian tube was replaced with a tube on a stent constructed from autogenous peritoneum from a suitable donor site. The effect of the surroundings environment of the new tissue system to which the peritoneum stem cells are now exposed was studied for 3, 6 and 12 months period in live animal models. The gross and histological studies revealed development of all the component of the wall of the fallopian tube. The lumen of the constructed peritoneal tube was well preserved in its whole length including the anastomotic sites. The scientific rationale of the working hypothesis on which the work is based, is discussed. PMID- 11218830 TI - A method for large-scale multiplication of Curculigo orchioides through bulbil formation from leaf explant in shake flask culture. AB - An efficient method has been developed for large-scale multiplication of Curculigo orchioides (Hypoxidaceae), an endangered medicinal plant, through direct bulbil formation from leaf explants in shake flask cultures. Leaf-segments (7 x 10 mm) were cultured in B5 liquid medium containing KNO3 (200 mgNL-1), (NH4)2SO4 (50 mgNL-1), benzyl adenosine (2.2 microM), adenine (0.11 mM), indole butyric acid (1.0 microM) and polyvinyl pyrrolidone (250 mgL-1). About 95% of explants produced maximum number of bulbils (546/flask at 6 weeks growth) in the medium. Shake flask cultures yielded 2737 bulbils/L medium whereas static cultures yielded 624 bulbils/L medium. Germination of bulbils was maximum (90.62%) on agar-gelled B5 medium containing benzyl adenosine (2.2 microM) and gibberellic acid (3.5 microM). Plantlets developed in vitro were successfully transferred to soil with a high rate of survivability (90%) and were comparable to natural population in growth and vigour. PMID- 11218829 TI - RH-5992--an ecdysone agonist on model system of the silkworm Bombyx mori. AB - RH-5992 is a novel synthetic non-steroidal ecdysteroid agonist with a high selectivity towards Lepidopteran species. The effect of ecdysone agonist RH-5992 on larval period, larval weight, silk gland weight and haemolymph protein profile were examined in the model organism, the larvae of silkworm, Bombyx mori. The LD50 values were found to be 16.21 and 12.01 micrograms/larva for 72 and 96 hr respectively. In the present study, three sublethal concentrations of 1/5th, 1/10th and 1/20th of LD50 at 72 hr were selected and applied on the mid-dorsal line of the silkworm B. mori. The maximum mortality of 35% was observed in the group which received the highest (3.2 micrograms/larva) concentration of RH-5992. The mortality rate was found to be dose dependent as well as time dependent. Interesting results were observed in haemolymph profile of the RH-5992 treated larvae as staining intensity of 30 kDa protein decreased significantly whereas the effect was not marked on other major proteins like storage proteins and vitellogenin polypeptides. From the results, it is confirmed that RH-5992 causes changes in larval characters and protein profile of silkworm B. mori. It is proposed that RH-5992 may cause negative effect specifically on reproductive characters like development of ovary and egg production due to decrease in 30 kDa protein. PMID- 11218831 TI - Micropropagation of terrestrial orchids, Anoectochilus sikkimensis and Anoectochilus regalis. AB - Two horticulturally important jewel orchids of the genus Anoectochilus were successfully micropropagated. Isolated nodes of A. sikkimensis collected from Sikkim in Eastern Himalayas and subsequently reared under nursery conditions and A. regalis collected from Western Ghats in Southern India were cultured for 12 weeks on Woody Plant Medium (WPM) to produce a maximum of 4.8 and 5.6 callus- free axillary shoots respectively at 95 and 98% efficiency. During reculture of the explants from in vitro raised shoots under the same conditions, the total number of shoots obtained from the nodes (21.4) and shoot tips (8.2) of A. regalis were significantly higher than those hardy and slow growing shoots of A. sikkimensis (12.3 and 4.3) respectively. Shoots (4-6 cm) were rooted in medium containing NAA (2.70 microM) and activated charcoal (0.2%). The rooted plants established at 95-98% rate in community pots after hardening. After 6 months, green house adapted community potted plants of A. regalis were transferred to natural forest habitat locally with 95 and 70% survival respectively after 12 months. The plants, established in community pots and native forest habitat were free from any morphological and growth defects. PMID- 11218832 TI - Non-cellulosic mixed linkage beta-D-glucan in sorghum, Sorghum bicolor (L.) Moench--localization and biological activity studies. AB - Fluorescence of Calcofluor and Congo Red was observed in stained sections of sorghum grain (Sorghum bicolor (L.) Moench), especially in the sub-aleurone cells indicating the presence of mixed linkage beta-D-glucan. Relatively less fluorescence intensity was observed in the single layered (approximately 20 microns thick) aleurone. Alkali extracted beta-D-glucan (fraction 2) of sorghum showed 30% activation of rat peritoneal macrophages (in vitro) at 100 micrograms ml-1 concentration in 10 min. This activation was found mediated mainly through PLA2 pathway. A phagocytic index k of 0.102 +/- 0.008 was observed in vivo carbon clearance test in mice in the group treated with fraction 2. Accumulation of colloidal carbon particles in spleen and liver of mice was moderate in this group, compared to control. PMID- 11218833 TI - Validity of mechanism of gene transfer in the process called conjugation in bacteria. AB - We have attempted a new evaluation of the process of conjugation in bacteria, because of some basic dissimilarities observed between this and that of eukaryotes, or plants and animals. Reference donor and recipient strains, widely used to prove conjugation in bacteria, were chosen; addition of DNase during the conjugation process, led to an unexpected but highly reproducible increase in the transconjugant colony counts (TCC; ca. > or = 1 log), when compared with that of the controls without DNase. Transconjugants were also obtained when the same live donors were substituted with the UV-killed ones although the TCC was very low initially. Contrarily, donors treated with DNA-intercalating agents, e.g. acridine orange or ethidium bromide, resulted in a complete failure to produce transconjugants. There was a quantitative relationship between the DNase used on donors and levels of DNA sugars/nucleotides/DNA, which possibly resulted from interaction between the DNase and DNA being present/produced on the donor surface. This may be indicative of what may actually happen in the donor recipient mixtures in the conjugation test proper, where the recipient DNase may activate a donor DNA production cycle. The evidences presented did not suggest that the donor DNA in the conjugation process is actually vestibuled through any intercellular conjugation passages, and is susceptible to the action of DNase or the intercalating dyes. PMID- 11218834 TI - Development of a computer software for analysis of SDS-PAGE protein fingerprints of bacterial isolates. AB - Protein fingerprinting is a widely used technique in epidemiological studies for typing bacterial strains. This study reports the development of a computer based gel analysis system. The system has the capability to analyse SDS-PAGE whole-cell protein profiles using digital image processing techniques. The software incorporates spatial and frequency domain operators for image enhancement, support for geometric correction of images and new algorithms for identification of strain tracks and protein bands. The system also provides facilities for correcting imaging defects for inter-gel comparison, similarity analysis, clustering and pictorial representation of results as a dendrogram. The software is highly interactive, user-friendly and can produce accurate results for differentiation of bacterial strains with minimal overhead of time. PMID- 11218835 TI - Bidder's organ extract induced anaphylaxis in experimental animals. AB - Bidder's organ (BO, a vestigeal organ), present in toad Bufo melanostictus (Schenider), is a characteristic feature of all male bufo. Its possible anaphylactic properties are investigated on experimental animals. BO extract produced both in vivo and in vitro anaphylactic reaction in guineapig. Dyspnoea and bronchoconstriction was a major cause of anaphylactic death. Blood histamine level was significantly increased in the anaphylactic animals. BO extract significantly released histamine from chopped lung preparation, an action antagonised by disodium chromoglycate. BO extract degranulated peritoneal mast cell in vitro. Passive cutaneous anaphylactic reactions were enhanced by BO extract and were significantly inhibited by disodium chromoglycate. Anaphylotoxin (identity not known) present in bidder's organ is probably involved in toad defence. PMID- 11218836 TI - Hypoglycaemic activity of extracts from soft corals of Andaman and Nicobar coasts in rats. AB - The ethylacetate extract of soft corals collected from Andaman and Nicobar Coasts were screened for hypoglycaemic activity in fasting rats. Rats were divided into 5 groups. Group I received 0.5 ml of 5% gum acacia suspension (control). Group II received the extract of Cladiella australis (CAS), at a dose of 250 mg/kg. Group III received the extract of Sinularia new species (SNS), at a dose of 75 mg/kg. Group IV received the extract of Lamnalia new species (LNS), at a dose of 400 mg/kg and Group V received the extract of 250MF-CBR-13 at a dose of 250 mg/kg. All extracts were administered orally. Blood samples, collected before the administration of test extracts and also at 2, 4, 6, and 8 hr after treatment, were analysed for glucose content. The percentage blood glucose reduction from that of control was also calculated. A very promising hypoglycaemic activity was observed in rats with CAS at 8 hr (42.3%), with SNS at 4 hr (28.34%) and 6 hr (40.6%), with LNS at 6 hr (32.38%) and with MF-CBR-13 at 6 hr (20.25%). PMID- 11218837 TI - Antinociceptive pattern of flavone and its mechanism as tested by formalin assay. AB - Flavone, dextrose and long swim stress exhibited antinociception. Degree of antinociception was greater with long swim stress as compared to flavone or dextrose. Combination of these treatments resulted in potentiation of antinociception. Naloxone (opioid antagonist; 5 mg/kg i.p.) antagonised flavone or long stress induced antinociception showing opioid medicated mechanism, however, failed to reverse the potentiated antinociceptive component recorded in long stressed animals which received flavone and dextrose. Antinociceptive activity of flavone, dextrose and long swim stress which was documented by acetic acid assay has been confirmed in the present study. Role for opioid system in this action has been demonstrated. Therefore, formalin test can also be considered as an useful assay procedure for testing flavonoids. However, like acetic acid assay this assay procedure also has the limitation that it is unable to detect minor changes in the degree of antinociception produced by physiological interventions such as long swim and dextrose. PMID- 11218839 TI - Effect of fumigation and juvenile hormone on oxygen consumption of the larvae of Corcyra cephalonica (Stainton). AB - Reduced effect of JH-I, JH-II and JH-III on oxygen consumption of II-V instars and increased effect on the oxygen consumption of VI instar larvae suggested that control of corcyra with juvenile hormones could be brought about only when applied to just emerged VI instar larvae. Similarly fumigation of juvenile hormone treated larvae could prove beneficial only at VI instar stage. The possibility of enhancing the effect of fumigant with pretreatment of JH will be futile as even only JH treated VI instar larvae develop into abnormal individuals which die later. PMID- 11218840 TI - Stress responses in two genotypes of mulberry (Morus alba L.) under NaCl salinity. AB - Changes in biomass yield rates, cell membrane stability (CMS), malondialdehyde (MDA) content and in the levels of physiological stress markers such as proline and glycine betaine in two high yielding genotypes (S1 and ATP, salt tolerant and salt sensitive, respectively) of mulberry under NaCl salinity were studied. Biomass yield rates and CMS were significantly decreased in both the genotypes under stress conditions. Per cent of decrease in biomass yield rate and CMS was relatively less in S1 than in ATP. Salt stress results a significant increase in the accumulation of proline, by 6-fold in S1 and 4-fold in ATP. Glycine betaine content was also increased significantly in stressed plants. However, the per cent increase was more in S1 than in ATP. The level of lipid peroxidation as indicated by MDA formation was greater in ATP than in S1. These results clearly support the better salt tolerant nature of S1 compared to ATP genotype. PMID- 11218838 TI - Purification and differentiation of three avian adenoviruses by restriction endonuclease analysis. AB - A rapid method of ultracentrifugation pelleting of avian adenovirus (AAV) from small volume of chloroform treated infected cell culture fluid or allantoic fluid was adapted for isolation of adenoviral DNA. The viral DNA extracted from semipurified viruses was found to be intact on agarose gel and pure enough (A260/280 = 1.85-1.92) for restriction enzyme analysis. Restriction endonuclease analysis of Indian strain of AAV serotype 1, AAV serotype 4 (group I AAVs) and egg drop syndrome-76 (EDS-76) virus genomes (group III AAV) with Hind III enzyme differentiated these viruses. The AAV serotype 1 and serotype 4 strain exhibited identical Hind III profile to European viral strains belonging to same serotypes however, the EDS-76 virus gave similar but not identical profile. The calculated genomic lengths for AAV serotype 1 and EDS-76 virus were approximately found to be 33.9 and 44.4 Kb, respectively. PMID- 11218841 TI - Ribosomal DNA repeat unit polymorphism in some pulses. AB - Restriction fragment length polymorphism (RFLP) of nuclear ribosomal RNA genes (rDNA) was carried out in some pulse species such as Lablab purpureus, Dolichos tribolus, Vigna bournii, V. grahmiana, V. unguiculata and V. wightii. Restriction endonuclease digestion and Southern blot analysis with wheat probe pTa 71 revealed a bewildering diversity. The fragment patterns produced by different enzymes such as Dpn II, Hind III, EcoRI and Bam H1 already illustrate considerable polymorphism. PMID- 11218843 TI - The effects of alcoholic compounds on the stability of type I collagen studied by differential scanning calorimetry. AB - The interaction between bovine tendon collagen and a series of homologous alcohols were investigated using a differential scanning calorimetry. For all alcoholic substances, as well as 2-hydroxyethyl methacrylate (HEMA), the concentration dependence of the denaturation temperature of collagen was observed, which showed a minimum at 30%. Clearly there are two opposing actions on the stabilization of the collagen structure; destabilization dominates over stabilization at lower concentrations, and vice versa at higher concentrations. The concentration dependence became greater for longer chain alcohols, while it was suppressed by the increased number of OH groups. The chain length-dependent surface tension may be related, which controls the permeation of the additives through the collagen fibers. Overall hydrophobicity, indicated by the hydrophile lipophile balance (HLB) numbers, suggests the importance of the hydrophobic effect in the interaction of collagen and alcoholic substances, including adhesive monomers such as HEMA. PMID- 11218844 TI - Effect of binary and ternary filler mixtures on the mechanical properties of composite resins. AB - The mechanical strength of experimental light cure composites containing binary filler mixtures with various combinations of irregular and spherical macrofillers in various mixes, and the microfilled ternary system fillers were measured. The compressive strength of the binary mixtures between different shaped fillers was not related to mixing ratios, although it significantly increased as the filler size decreased. The mixing ratio was immaterial within the irregular filler mixture. The compressive strength of the binary mixtures within the spherical fillers increased as the mixing ratio increased while the filler size was relatively large, then the mixing ratio became insignificant as the filler size decreased under 1.4 microns. The compressive strength of the microfilled ternary fillers increased with the decrease in the macrofiller size and with the increase in the mixing ratio. A large diametrical tensile strength was found in several microfilled ternary mixtures containing different shaped macrofillers. PMID- 11218842 TI - Mercury evaporation from amalgams with varied mercury contents. AB - This study examined the relationship between mercury content and mercury evaporation from amalgams during setting. Two different types of commercial high copper amalgams (single composition and admixed types) were used. Cylindrical specimens of each amalgam were prepared with five different mercury contents according to ADA Specification No.1. Specimens were also prepared by hand condensation. Mercury evaporation from amalgam specimens maintained at 37 degrees C was measured using a gold film mercury analyzer from 10 min after the end of trituration until the mercury concentration in air reached an undetectable level. The mercury content more clearly influenced the mercury evaporation from the admixed type amalgam specimens when the mercury content decreased below the manufacturers' recommended trituration conditions. Triturating with less mercury than the manufacturers' recommended amount cannot lower the evaporation of mercury from freshly made amalgam. Proper condensing procedures can minimize the mercury evaporation from the amalgam surface. PMID- 11218845 TI - Estrogenic activity of dental materials and bisphenol-A related chemicals in vitro. AB - Twenty-eight chemicals used as dental materials and bisphenol-A related chemicals were diluted with DMSO to concentrations ranging from 10(-7) to 10(-3) M and tested for estrogenicity. Bisphenol-A (BPA), bisphenol-F (BPF) and bisphenol-A bischloroformate (BPACF) showed estrogenic activity using the yeast two-hybrid system, and BPA, BPF, BPACF and bisphenol-S (BPS) showed estrogenic activity using the fluorescence polarization system. However, none of the remaining chemicals and none of the dental materials showed any activity at concentrations between 10(-7) and 10(-3) M. Although BPA, BPF, BPACF, bisphenol-A-dimethacrylate and BPS showed estrogenic activity in the E-screen test, the remaining chemicals did not. Thus, most of the chemicals showed consistent results, either positive or negative, by the three testing methods, while two chemicals showed conflicting results. Further studies, together with in vivo and epidemiological examinations, are required. Elucidation of the structure-activity relationships of these chemicals is also needed to estimate the estrogenicity of a chemical from its structure. PMID- 11218846 TI - Analysis of major components and bisphenol A in commercial Bis-GMA and Bis-GMA based resins using high performance liquid chromatography. AB - The purpose of this study was to examine the quality of commercially available Bis-GMA because concerns about Bis-GMA and Bis-GMA-based resins have been recently expressed in dentistry. Four major components and bisphenol A, which is a compound of recent controversy, were quantitatively analyzed using high performance liquid chromatography (HPLC) in three commercial Bis-GMA and six Bis GMA-based composite resins. The contents of genuine Bis-GMA, Iso-bis-GMA, Bis-GMA H, and Bis-GMA-M as well as the total content of the four monomers were 45.7 57.5%, 19.9-26.2%, 1.8-5.0%, 0.6-15.0% and 83.7-85.6% in the commercial Bis-GMAs, or 3.8-9.1%, 1.7-4.3%, 0.1-0.5%, 0.1-2.0% and 5.8-14.0% in composite resins, respectively. There were some differences in the composition of the major components between domestic and foreign materials. Bisphenol A contents in the unpolymerized composite resins were 1.5-10.2 micrograms/g resin. PMID- 11218847 TI - Corrosion resistance of the Pt-Fe-Nb magnets for dental-casting. AB - Magnetic attachments have been used in clinical dental practice, but there is some difficulties associated with removable bridges. One possible solution is to make whole bridges of Pt-Fe magnet alloys and its abutment out of magnetic stainless steel by casting. In terms of castability and magnetic properties, the promising composition of the Pt-Fe-Nb magnet alloy is Pt-30.0 mass% Fe-0.6 mass% Nb and Pt-30.0 mass% Fe-0.5 mass% Nb-0.03 mass% Si. In the present study, the corrosion resistance of these alloys was investigated based on the elusion test, electrochemical behavior and surface characterization by EPMA analysis. The released elements from the Pt-Fe-Nb magnets were mainly Fe ions in quantities similar to that of stainless steel for biomedical use, and the Pt-Fe-Nb magnet alloy, the Pt-Fe-Nb-Si magnet alloy and platinum resembled each other in electrochemical behavior. The present findings suggest, that the Pt-Fe-Nb magnet alloy provides excellent corrosion resistance and has important clinical dental applications. PMID- 11218850 TI - New partition technique for two-chamber pressure casting unit for titanium. AB - Although titanium has been widely used in prosthetic appliances, such as cast removable partial denture frameworks, high quality castings are still difficult to obtain. This study proposes a new partition technique using a metal foil for improving castability of a two-chamber pressure casting unit. The metal foil was formed beforehand to bring it in contact with the mold crucible wall so that no clearance was left behind it. Using this formed foil, the mold cavity can be completely isolated from the upper chamber and can be maintained in a vacuum even after the rupture of the foil. Accordingly, a large casting force is generated very quickly, and as a result, castability is expected to be significantly improved. This expectation was confirmed by the experiments using wax patterns including thin plate and mesh plate. PMID- 11218848 TI - Study of resin-bonded calcia investment: Part 1. Setting time and compressive strength. AB - This study was carried out to develop a new titanium casting investment consisting of calcia as the refractory material and a cold-curing resin system as the binder. The setting time of the investment was investigated under different N,N-dimethyl-p-toluidine (DMPT) contents in methyl methacrylate monomer (MMA) and benzoyl peroxide (BPO) contents in calcia without any sintering agent. The effects of the sintering agents, which were calcium fluoride (CaF2) and calcium chloride (CaCl2), on the compressive strength of the investments were investigated at room temperature before and after heating to two different temperatures. The shortest setting time (68 minutes) of the investment was obtained at 0.37 DMPT/BPO (1.5 vol% /1.0 mass%) ratio by mass. The highest strength (16.5 MPa) was obtained from the investment which contained 2 mass% CaF2 and was heated to 1,100 degrees C. It was found that the developed calcia investment containing 2 mass% CaF2 has a possibility for use in titanium castings. PMID- 11218849 TI - Development of Ag-Pd-Au-Cu alloy for multiple dental applications. Part 1. Effects of Pd and Cu contents, and addition of Ga or Sn on physical properties and bond with ultra-low fusing ceramic. AB - Ag-Pd-Au-Cu quaternary alloys consisting of 30-50% Ag, 20-40% Pd, 10-20% Cu and 20% Au (mother alloys) were prepared. Then 5% Sn or 5% Ga was added to the mother alloy compositions, and another two alloy systems (Sn-added alloys and Ga-added alloys) were also prepared. The bond between the prepared alloys and an ultra-low fusing ceramic as well as their physical properties such as the solidus point, liquidus point and the coefficient of thermal expansion were evaluated. The solidus point and liquidus point of the prepared alloys ranged from 802 degrees C to 1142 degrees C and from 931 degrees C to 1223 degrees C, respectively. The coefficient of thermal expansion ranged from 14.6 to 17.1 x 10(-6)/degrees C for the Sn- and Ga-added alloys. In most cases, the Pd and Cu contents significantly influenced the solidus point, liquidus point and coefficient of thermal expansion. All Sn- and Ga-added alloys showed high area fractions of retained ceramic (92.1-100%), while the mother alloy showed relatively low area fractions (82.3%) with a high standard deviation (20.5%). Based on the evaluated properties, six Sn-added alloys and four Ga-added alloys among the prepared alloys were suitable for the application of the tested ultra-low fusing ceramic. PMID- 11218851 TI - WDX study of resin-dentin interface on wet vs. dry dentin. AB - The purpose of the present study was to determine the resin-dentin Interface conditions in Wet vs. Dry Dentin. Dentin disks were prepared from extracted human premolars. Sectioned dentin surfaces were used for SEM studies of wet vs. dried acid-etched dentin. These specimens were cut perpendicular to the surface into two equal halves. One-half of the sectioned specimen was observed by SEM in three treatment groups and the other half was observed for micromorphological differences in the resin-dentin interface using Wavelength Dispersive X-ray Spectrometer (WDX). SEM photomicrographs of the dentin surface showed the collapse of collagen fibrils in the demineralized layer and enlargement of the tubule orifices. A collagen rich layer approximately 8-10 microns thick (WDX) was observed at the resin-dentin interface when treated with the conventional dry bonding technique. Dentin surfaces treated by the wet-bonding technique (SB), as observed by SEM, showed an uncollapsed collagen layer, while the collagen-rich layer was approximately 1-2 microns thick (WDX). The present findings suggest that moist bonding is required for optimum infiltration of adhesive resin into the demineralized layer. PMID- 11218852 TI - [Effects of isoprenaline on apoptosis related gene expression in rat myocardium cells]. AB - AIM: To study the relationship between acute myocardial ischemia rat induced by isoprenaline (Iso) and expression of some apoptosis related genes in myocardium. METHODS: Acute myocardial ischemic rat model was induced by subcutaneous injection of large doses of Iso. The myocardial expression of apoptosis related genes, Fas, CPP32, Bcl-2 and Bax, were detected with RT-PCR method. The influences of aloperine (Alo, 20 mg.kg-1) and propranolol (Prop, 2 mg.kg-1) on apoptosis related genes were also investigated by the same method. RESULTS: Myocardial expression of Fas, CPP32 and Bcl-2 were increased in acute myocardial ischemic rats, but no significance was detected in Bax expression. Both Alo and Prop were shown to decrease the expression of Fas and CPP32, and increase expression of Bcl-2. Prop also showed down regulated effect on expression of Bax. CONCLUSION: Subcutaneous injection of large doses of Iso was shown to induce expressions of apoptosis related genes in rat myocardium, which were also influences by Alo and Prop. PMID- 11218853 TI - [The effect of melatonin on enhancing immune function and inhibiting the ability of NO over-release in morphine dependent mice]. AB - AIM: To observe the effects and mechanism of melatonin (MT) on the immune function of morphine dependent mice. METHODS: A physical dependent mice model was established by repeated subcutaneous injection of morphine. The intensity of morphine withdrawal syndrome was evaluated according to the weight of immune organs, the proliferation reaction of stimulated splenic lymphocytes by Con A, the phagoindex of blood primed macrophages and the content of NO induced in the peritoneal macrophage (pM phi). RESULTS: MT reversed the inhibitory effect of morphine on the proliferation ability of splenic lymphocytes and enhanced the phagocytosis of macrophages of morphine dependent mice obviously and prevented the over-release of NO from pM phi. The enhancing effects of MT on the phagocytosis can be prevented by naloxon. CONCLUSION: MT can significantly enhance the immune function of morphine dependent mice and inhibit NO excessive release from pM phi. PMID- 11218854 TI - [Expression of FAS and FASL genes in brain and effect of flunarizine on these expressions in rats after global ischemia-reperfusion]. AB - AIM: To explore the expression of Fas and FasL genes after ischemia-reperfusion in rats and the effect of flunarizine. METHODS: Ischemia was induced by four vessel occlusion for 30 min following reperfusion in rats. The biopsy tissues from brain were immunohistochemically assayed with Fas and FasL genes polyclonal antibody. RESULTS: The expression of Fas was increased as early as 6 h after the onset of reperfusion. The peak of the expression of Fas occurred 24-48 h after ischemia-reperfusion. The expression of FasL was observed 12 h after ischemia reperfusion and peaked at 48-72 h. The expression of Fas and FasL gene was quite obvious in the cortex and hippocampus CA1, the more sensitive areas to ischemic injury. Flunarizine i.p. 10 mg.kg-1 and 20 mg.kg-1 obviously inhibited the expression of Fas and FasL in dose-dependent manner. CONCLUSION: Expression of Fas and FasL in cerebral cortex and hippocampus can be induced by global ischemia reperfusion. Flunarizine significantly inhibited the expression of Fas and FasL genes following ischemia-reperfusion. PMID- 11218855 TI - [Effect of heparinoid derived from porcine duodenum on the proliferation of cultured smooth muscle cells]. AB - AIM: To study the antiproliferative effect of haparinoid derived from porcine duodenum (heparinoid) on cultured vascular smooth muscle cells. METHODS: Cultured bovine aortic smooth muscle cells (BASMCs) of 5-10 passages were seeded into 24 and 72-well cluster culture plates and were synchronized by 48 h serum deprivation. Then, the cells were re-stimulated by serum repletion with or without heparinoid. The antiproliferative effect of heparinoid was evaluated by crystal violet staining and MTT assay 72 h after serum repletion. To study the drug action on cytomorphological changes, three kinds of cells [quiescent cells, cells treated with 10% fetal calf serum (FCS) with or without heparinoid] were observed by transmission electron microscopy. After synchronized and re stimulated as above, BASMCs were treated with heparinoid 0.8 mg.mL-1 at selected points during serum repletion. The cells were harvested at specified times after serum repletion, then cellular DNA contents (to estimate the proportions of cells in different phases of the cell cycle) and the contents of alpha-actin, c-myc and c-fos proteins were measured by flow cytometry. RESULTS: Heparinoid was shown to inhibit the proliferation of BASMCs induced by 10% FCS. The inhibitory effect was weakened when heparinoid was added 2 h after serum repletion, and there was no antiproliferative effect when heparinoid was added 12 h after serum repletion. Electron micrographs showed that cells treated with 10% FCS and heparinoid expressed a contractile phenotype, while cells treated with 10% FCS only expressed a synthetic phenotype. Flow cytometry study showed remarkable increase of alpha-actin, and decrease of c-myc and c-fos proteins in the cells treated with heparinoid. CONCLUSION: Heparinoid was found to inhibit the proliferation of BASMCs. The antiproliferative effect occurred at the early phase of the cell cycle. It might be due to the drug's influence on cell phenotype modulation and the down regulation of c-myc and c-fos proto-oncogenes expression. PMID- 11218857 TI - [New triterpenoid saponins from Anemone begoniifolia]. AB - AIM: To study the triterpenoid saponins in the whole plants of Anemone begoniifolia Levl. et Vant. METHODS: Methanol extraction, normal and reversed phase silica gel column chromatography and various spectral analysis were used to isolate and determine the structures of the triterpenoid saponins. RESULTS: Four triterpenoid saponins were idenetified as: 3-O-beta-D-glucopyranosyl(1-->2)-alpha L-arabinopyranosyl oleanolic acid 28-O-alpha-L-rhamnopyranosyl (1-->4)-beta-D glucopyranosyl (1-->6)-beta-D-glucopyranoside (1), 3-O-beta-D-glucopyranosyl (1- >3)-alpha-L-arabinopyranosyl oleanolic acid 28-O-alpha-L-rhamnopyranosyl (1-->4) beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranoside (2), 23-O-methyl malonyl hederagenin 28-O-alpha-L-rhamnopyranosyl (1-->4)-beta-D-glucopyranosyl (1-->6) beta-D-glucopyranoside (3) and 3-O-methyl malonyl hederagenin 28-O-alpha-L rhamnopyranosyl (1-->4)-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranoside (4). CONCLUSION: Compunds 2, 3 and 4 are new compounds and named as begoniifolides A, B and C, respectively. PMID- 11218858 TI - [Studies on the chemical constituents of Murraya kwangsiensis]. AB - AIM: To investigate the chemical constituents of Murraya kwangsiensis. METHODS: Compounds were isolated by silica gel column chromatography and TLC method, respectively. Structures of compounds were elucidated by spectral (UV, IR, MS, 1HNMR and 13CNMR) analysis. RESULTS: Five carbazole alkaloids and two other compounds were isolated and identified. Six of them are known compounds: murrayafoline A, murrayanine, koenine, isomahanine, palmitic acid and beta sitosterol. One is a new alkaloid, named kwangsine. CONCLUSION: A new alkaloid, named kwangsine, was isolated from Murraya kwangsiensis Var. Six known compounds were isolated from this plant for the first time. PMID- 11218856 TI - [One-pot synthesis of dl-naproxen by rearrangement]. AB - AIM: To synthesize dl-naproxen by rearrangement method. METHODS: dl-Naproxen was synthesized by halogenation, ketalization, rearrangement and hydrolysis, using cupric halide as halogenation agent. RESULTS: Total yields were 74.0%-92.6% based on 6-methoxy-2-propionyl naphthalene. CONCLUSION: Total yield was higher by one pot rearrangement approach. PMID- 11218859 TI - [Studies on metabolite of beta-elemene in rat bile]. AB - AIM: To study the metabolite of beta-elemene in the bile of rat. METHODS: After i.v. 100 mg.kg-1 beta-elemene, the metabolite in rat bile was extracted by ether. Mass spectrometry, nuclear magnetic resonance, infrared spectrometry and ultraviolet spectrometry were used to analyze the metabolite of i.v. beta-elemene in rat bile. RESULTS: It was confirmed by nuclear magnetic resonance that the methyl of No. 11 carbon connecting with No. 10 carbon of a metabolite in rat bile was oxidized to be aldehyde. The molecular weight of the metabolite was 218 which detected by mass spectrometry. Infrared spectrometry and ultraviolet spectrometry proved that the aldehyde existed in the metabolite. The structure of the metabolite in bile of rat was identified, that was 1-methyl-1-ethenyl-2 isopropenyl-4-isopropenyl aldehydohexamethylene. CONCLUSION: The biotransformation of beta-elemene exists in vivo. PMID- 11218860 TI - [Foundational study of subcritical water chromatography]. AB - AIM: To study the subcritical water chromatographic discipline of compounds with medium and high polarity on the capillary and packed column. METHODS: A packed and capillary subcritical water chromatography-FID detection system was built up. Six alcohols were well separated on a C18 column and the influence of temperature on chromatographic behavior of alcohols with different polarity was studied. The influence of temperature and pressure on chromatographic behavior of benzoic acid and gensenoside Rg1 on a SE-54 capillary column were also studied. RESULTS: Increasing temperature resulted in the decreasing polarity of mobile phase, shortened retention times of components separated, narrowed peak shape and improved tailing as well. CONCLUSION: Temperature programming could be used successfully to separate compounds with various polarity selectively. Thermostable capillary column could enlarge the range of temperature even more. PMID- 11218861 TI - [Pharmacokinetics of topically applied in-situ-forming gels of fluconazole in rabbit eyes]. AB - AIM: To study the pharmcokinetics of fluconazole (FCZ) in the aqueous humors and tears of New Zealand white rabbits following topically applied in-situ-forming gels of 0.5% FCZ (ISG-FCZ) and 0.5% FCZ eye drops to rabbit eyes. METHODS: The rabbit tears and aqueous humors were obtained and quantified at different times after topically applying single dose of ISG-FCZ and FCZ eye drops to the rabbit eyes. The drug levels were assayed by megabore capillary gas-liquid chromatography with nitrogen-selective detector. The pharmacokinetic parameters were calculated with nonlinear least square method with computer. RESULTS: FCZ concentrations in rabbit tears within 180 min after applying ISG-FCZ were found to be significantly higher compared with those of FCZ eye drops. The FCZ levels in the aqueous at 10, 30, 60, 90 and 120 min after applying ISG-FCZ are significantly higher compared with FCZ eye drops. The time for arriving peak concentration (Tmax) and the area under concentration (AUC)-time curve as well as the half-life (T1/2) of FCZ in rabbit aqueous humors were markedly higher after application of ISG-FCZ. The peak levels in the aqueous humors showed no difference between the two groups. CONCLUSION: The ISG-FCZ, which upon exposure to physiological conditions will shift the gel phase, can significantly extend FCZ release and increase the precorneal residence time of the drug, thus enhance ocular bioavailability compared with FCZ eye drops. PMID- 11218862 TI - [Analysis of phenylethanoid glycosides in the extract of herba Cistanchis by LC/ESI-MS/MS]. AB - AIM: To analyze the phenylethanoid glycosides in Cistanche deserticola Y. D. Ma and its alternatives. METHODS: An HPLC/MS/MS method has been developed for the analysis of seven kinds of phenylethanoid glycosides in Cistanche deserticola Y. D. Ma, C. salsa (C. A. Mey) G. Beck and C. tubulosa (Schenk) R. Wight. The [M - H]- ions were observed for five standards and Cistanche extracts. The glycosidic linkages, the core, and the attached sugar (s) of the phenylethanoid glycosides can be determined from the collision-induced dissociation spectra of the molecular. RESULTS: Seven kinds of phenylethanoid glycosides (echinacoside, acteoside, cisacteoside, isoacteoside, 2'-acetylacteoside, cistanoside A, osmanthuside B) in Cistanche deserticola Y. D. Ma, six kinds (echinacoside, acteoside, cisacteoside, isoacteoside, 2'-acetylacteoside and cistanoside A) in C. salsa (C. A. Mey) G. Beck and five kinds (echinacoside, acteoside, cisacteoside, isoacteoside and 2'-acetylacteoside) in C. tubulosa (Schenk) R. Wight were detected. CONCLUSION: The difference of the relative distribution of these phenylethanoid glycosides in each extract was found out. Phenylethanoid glycosides are the specific constituents in Cistanchis, which can be used to distinguish different species in Genus Cistanchis. PMID- 11218863 TI - [Use of high-field nulear magnetic resonance spectroscopy for the analysis of stereoselective metabolites of ibuprofen (R)-enantiomer in rat urine]. AB - AIM: To study the metabolic chiral inversion and chiral metabolites of R-(-) ibuprofen. METHODS: Following administration of R-(-)-ibuprofen (250 mg.kg-1), analysis was performed on rat urine purified extracts obtained by solid phase extraction onto C-18 bonded silica gel, then the metabolites of ibuprofen were detected and identified by 1HNMR spectroscopy. RESULTS: Except for a little ibuprofen, there were 2'-hydroxy-ibuprofen and its glucuronide, 1'-carboxy ibuprofen glucuronide and ibuprofen glucuronide in rat urine. 2'-hydroxy ibuprofen is the main metabolite. 1'-carboxy-ibuprofen glucuronide and ibuprofen glucuronide were diastereoisomers. CONCLUSION: There was the phenomenon of metabolic chiral inversion, whereby the R-enantiomer is transformed in vivo to its active S-antipode via an unusual process. PMID- 11218864 TI - [Detection of impurities in DNA samples by using the convolution spectrum method]. AB - AIM: To detect the presence of phenol, amino acids and endotoxin in DNA preparations. METHODS: By using the convolution curve transformation technology, correlation coefficient discriminant which was put forward by spectrum space theory and computer information process technology, impurities in DNA samples were detected. RESULTS: The convolution spectrum method compared with A260/A280 ratio method and second-derivative absorption spectrum method could be used for the semiquantitative determinations of impurities in DNA samples and the results were satisfactory. CONCLUSION: The method was simple, convenient, fast and valuable to the biochemical analysis. PMID- 11218865 TI - [Study on preparation and pharmacodynamics of insulin-loaded polyester microparticles]. AB - AIM: To investigate the possibility of using poly (epsilon-caprolactone-block-D, L-lactide) (PLCA) as a kind of materials to prepare the microparticles drug carrier. METHODS: PCLA-MP (microparticle, MP) was prepared by double emulsification solvent evaporation method. Its morphology was examined by scanning electron microscope. Its size diameter was examined by particle analyser. Insulin (INS), as a model drug, was then encapsulated into PCLA-MP (INS PCLA-MP). HPLC method was established for determining INS in INS-PCLA-MP. An "antibody-capture" procedure was devised for investigating encapsulation mechanism. The in vitro release behaviour of INS-PCLA-MP was determined in phosphatic buffer solution (pH 7.4). The diabetic rat model was established and blood glucose levels were measured using glucose oxidase (GOD-PAP) method to evaluate the hypoglycaemic effects after subcutaneous administration of INS-PCLA MP. The pharmacological bioavailability (PBA) of INS-PCLA-MP was calculated from the area above the curve (AAC) in contrast with INS-solution. RESULTS: The mean diameter of INS-PCLA-MP was 1.9 microns, while the encapsulation ratio of INS reached to 76.46%. Only 18.25% encapsulated INS was on the surface of the microparticles, it could be measured by "antibody-capture" experiment. The in vitro release curve of INS-PCLA-MP consists of initial rapid release stage followed by slower exponential stage. In pharmacodynamic studies, after subcutaneous administration of INS-PCLA-MP 12 u.kg-1, the hypoglycaemic effect was significant. The PBA of INS-PCLA-MP was 123.08%. CONCLUSION: PCLA might become a new drug carrier material in the future. PMID- 11218866 TI - [Study on preparation and biodistribution of PEG-immunoliposomes with active carboxylic terminals]. AB - AIM: In order to accumulate into its target specifically, the immunoliposomes must possess two characteristics: specific target efficiency to its target cells and prolonged circulation in blood. A new type of polyethylene glycol (PEG) immunoliposomes carrying monoclonal antibodies at the distal end of PEG chains should be developed. METHODS: A dipalmitoylphosphatidylethanolamine (DPPE) derivative of PEG with carboxyl group (DPPE-PEG3000-COOH) was newly synthesized. Small unilamellar liposomes were prepared from egg phosphatidyl choline and cholesterol (5:4, mol/mol) containing 6 mol% DPPE-PEG3000-COOH using reverse phase evaporation method followed with bath sonication. Monoclonal antibody of human bladder cancer cell (BDI-1), which is highly specific to human bladder cancer cell, was conjugated to PEG-liposomes as well as mouse IgG at the distal end of polyethylene glycol chain. Doxorubicin was entrapped into these immunoliposomes by remote (NH4)2SO4 gradient loading method. The specific targeting efficiency of these immnoliposomes was tested by cytotoxicity test in vitro, enzyme-linked immune sorbent assay (ELISA) and indirect fluorescent immunoassay. Its biodistribution was carried out in mice. RESULTS: The specific targeting efficiency of BDI-1 immunoliposomes (BDI-1-IML) to EJ cells has been demonstrated, in contrast to the nonspecific human colon carcinoma cells (LOVO). PEG-liposomes linked with mouse IgG (mouse-IgG-immunoliposomes, IgG-IML) displayed lower reticulo-endothelial systems (RES) uptake and longer circulation time than liposomes without PEG after intravenous injection. CONCLUSION: The long circulation of these PEG-immunoliposomes in vivo, combined with its specific targeting efficiency demonstrated in vitro, guarantees the positive targeting efficiency of these immunoliposomes to its target carcinoma in vivo. PMID- 11218867 TI - [Antifungal effect of three natural products on the genetic substance of Saccharomyces cerevisiae GL7 and Prototheca wickerhamii]. AB - AIM: To investigate the antifungal effect of three natural products on the genetic substance of Saccharomyces cerevisiae GL7 and Prototheca wickerhamii. METHODS: The normal and treated cells were observed by confocal laser scanning microscope (CLSM) and image analysis to quantitatively described the cell morphology, area, DNA and RNA content. RESULTS: The morphology, area, DNA and RNA contents were changed greatly in the treated cells. CONCLUSION: Solasodine, 4' hydroxy-3, 5-dimethoxystilbene and dictamnine directly or indirectly interfered the synthesis and function of genetic substance in S. cerevisiae and P. wickerhamii. PMID- 11218868 TI - [Selective isolation of isopsoralen from crude extract of Psoralea corylifolia. L by using inclusion method of host-guest molecules]. AB - AIM: To isolate the chemical components from extracted crude of Psoralea corylifolia L. METHODS: Applicate the function of molecular recognition in supramolecular chemistry, use 1,1,6,6-tetraphenylhexa-2,4-diyne-1,6-diol as the host molecule and chemical components in extracted crude of Psoralea corylifolia L. as guest molecules, which represent different from either in sort, quantity and sites of function groups or in structural topological character, 1,1,6,6 tetraphenylhexa-2,4-diyne-1,6-diol could selectively form inclusion compound with component endowed with interactional complementarity and isolate as crystalline from the extracted crude of Psoralea corylifolia L. RESULTS: The isopsoralen as guest molecule is selectively included by 1,1,6,6-tetraphenylhexa-2,4-diyne-1,6 diol in inclusion crystal and removed by acetone from the inclusion compound and total yield is 0.18%. Isopsoralen is determined by UV, IR, 1HNMR and MS and its inclusion compound is determined by means of IR, powder XRD and single crystal XRD. The isolation effect is analyzed by GC/MS. CONCLUSION: The method is simple and selective for isolation isopsoralen from extracted crude of Psoralea corylifolia L. PMID- 11218870 TI - [Comparison between colorimetry and HPLC on the stability test of roxithromycin]. AB - AIM: To compare the stability of roxithromycin in solutions of different pH. METHODS: Roxithromycin solutions of different pH were prepared with water, simulate intestinal fluid (SIF) and simulate gastric fluid (SGF) shown to be the stability of these solutions were tested by colorimetry and HPLC. RESULTS: Roxithromycin was stable in water, SGF and SIF determined by colorimetry. However, it was found to be stable only in water and SIF but unstable in SGF as determined by HPLC. CONCLUSION: Roxithromycin is unstable in acidic medium like SGF. The metabolite of roxithromycin showed unfavorable interference on the assay of roxithromycin when colorimetry was used. Colorimetry can not be used for the determination and assay of roxithromycin in acidic solution like SGF. PMID- 11218869 TI - [Determination of ecdysterone in Achyranthes bidentata Bl. and its activity promoting proliferation of osteoblast-like cells]. AB - AIM: To study the activity of ecdysterone from Achyranthes bidentata Bl. (AB) promoting proliferation of osteoblast-like (OB-like) UMR106 cells and to determine its content in AB by HPLC method. METHODS: Ecdysterone isolated from AB was cultured with OB-like cells UMR106 together in vitro and the proliferation of OB-like cells was determined by MTT assay. The chromatographic conditions for determining ecdysterone included an ODS column (250 mm x 4.6 mm, 5 microns), a mobile phase consisting of a mixture of water-acetontrile-tetrahydrofuran (86:11:3), detection wavelength of 243 nm, and column temperature of 27 degrees C. Phenacetin was used as the internal standard. RESULTS: The ecdysterone from AB had significant activity promoting proliferation of OB-like cells, the proliferation was promoted by 41% (n = 3). The average recovery of ecdysterone was 96.2% (RSD = 2.1%), the calibration was linear in the range of 30-300 micrograms.mL-1 (gamma = 0.9998). CONCLUSION: Ecdysterone was screened quickly by cultivating with OB-like cells together in vitro. The HPLC method is accurate, fast and reproducible for the determination of ecdysterone in AB. PMID- 11218871 TI - [Progress in studies on small molecule cytokine mimetics]. PMID- 11218872 TI - [Evaluation of immune prophylaxis of recombinant urease subunit of Helicobacter pylori]. AB - OBJECTIVE: To evaluate the immune prophylaxis of recombinant urease subunit A or B (rUreA or rUreB). METHODS: The BALB/C mice were divided into seven groups: negative control group, control group with CTB, control group with rUreA, control group with rUreB, experimental group with rUreA + CTB and experimental group with rUreB + CTB, experimental group with sonicate + CTB, which were gastrically inoculated with 150 ml PBS, 5 micrograms CTB, 50 micrograms rUreA, 50 micrograms rUreB, 50 micrograms rUreA + CTB, 5 micrograms rUreB + CTB and 400 micrograms sonicate + 5 micrograms CTB, respectively. Two weeks later, the mice were gastrically infected with H. pylori (10(7)-10(8) CPU per time). 4, 8 and 12 weeks later, the mice were killed and the immune protection of PBS, CTB, rUreA, rUreB, rUreA + CTB, rUreB + CTB and sonicate + CTB were evaluated by the presence of H. pylori in gastric tissue stained with Giemsa by microscopy. The mice in the side effecting groups of rUreA + CTB and rUreB + CTB were not infected with H. pylori. 12 weeks later, the mice in the two groups were killed, and the side effects of rUreA + CTB and rUreB + CTB were evaluated by the infiltration of inflammation cells in gastric tissue stained with HE by microscopy. RESULTS: The mice gastrically inoculated with CTB, rUreA or rUreB had significantly less H. pylori. The immune protective effect of rUreA, rUreB or sonicate of H. pylori combined with CTB was stronger than that of rUreA, rUreB or sonicate of H. pylori alone. The immune protective effect of rUreA + CTB occurred later than that of rUreB + CTB or sonicate of H. pylori + CTB. The mice immunized with rUreA + CTB, rUreB + CTB or sonicate of H. pylori + CTB were not completely protected against H. pylori infection. The mice immunized with rUreA + CTB, rUreB + CTB or sonicate of H. pylori + CTB were less infected with H. pylori, and had mild inflammation of gastric tissue. CONCLUSION: Mice immunized with rUreA + CTB, rUreB + CTB or sonicate of H. pylori + CTB could not be completely protected against H. pylori infection and have alleviated inflammation of gastric tissue. PMID- 11218874 TI - [Evaluation and comparison of the Helicobacter pylori stool antigen test and the gastric mucosal antigen test]. AB - OBJECTIVE: To evaluate the reliability of an enzyme-linked immunosorbent assay by the Helicobacter pylori (H. pylori) stool antigen test for the detection of H. pylori infection. METHODS: Stool specimens were collected from 224 patients who received upper gastrointestinal endoscopic examination for gastrointestinal symptoms. H. pylori status was evaluated by five different tests: culture, histology, biopsy rapid urease test, H. pylori stool antigen test, and H. pylori gastric active mucosal antigen test (parts of the patients). A commercial kit using an enzyme-linked immunosorbent assay was used to examined H. pylori antigen in the stool or in the gastric active mucosa. H. pylori status was defined as positive when two of the three tests (culture, histology and biopsy rapid urease test) were positive. RESULTS: 137 patients were diagnosed as H. pylori-positive. The H. pylori stool antigen test was positive in 143 patients and negative in 81 patients. The sensitivity and specificity were 96.4% and 87.4%, respectively. The overall accuracy was 92.9%. 39 patients were examined H. pylori antigen in the gastric active mucosa, and 27/39 were diagnosed as H. pylori-positive. The H. pylori gastric active mucosal antigen test was positive in 28 patients and negative in 11 patients. The H. pylori stool antigen test was positive in 30 patients and negative in 9 patients. The corresponding rate between gastric active mucosa and stool was 94.9%. CONCLUSION: The H. pylori stool antigen test is a simple, non-invasive method for accurate diagnosis of H. pylori infection. PMID- 11218873 TI - [The evaluation of cagA and other vaccine candidate proteins of Helicobacter pylori on T cell apoptosis mediated by Fas/Fas ligand interaction]. AB - OBJECTIVE: To evaluate the effect of several surface proteins of Helicobacter pylori (H. pylori) on inducing apoptosis of T cells through the modulation of Fas/Fas ligand (FasL) interaction and to provide information on the screen of safe and effective immunogen for H. pylori vaccine. METHODS: T cell apoptosis induced by cagA+ and isogenic cagA knockout strain, recombinant urease, HpaA and outer membrane proteins, Hop25, Hop35 and Hop38 was detected by JAM assay. Flow cytometry was used to evaluate the increase in FasL expression on T cells under the stimulation of these bacterial proteins. Metalloprotease inhibitor, 1, 10 Phenanthroline (PHE) and protein synthesis inhibitor, emetine, were used to change the activity of FasL to confirm the association of FasL with H. pylori mediated killing toward T cells. RESULTS: The effect of cagA+ H. pylori was stronger in both the induction of apoptosis and FasL expression of T cells than that of cagA knockout strain. H. pylori urease could not kill T cell, while Hop38 had the strongest effect among the tested H. pylori proteins on the induction of T cell apoptosis through increasing FasL expression. Metaloprotease inhibitor could increase the killing of T cells induced by H. pylori because of its ability to prevent the cleavage of membrane-bound FasL protein. On the other hand, emetine could decrease H. pylori mediated killing by inhibiting of FasL synthesis on T cells. CONCLUSION: cagA and Hop38 protein might be involved in the negative regulation of T cell growth through upregulating FasL expression urease and other Hop proteins tested might be safe and effective to be used as the antigens for H. pylori vaccine. PMID- 11218875 TI - [Variable number of tandem repeats as an evidence of engraftment status after allogeneic peripheral blood stem cell transplantation]. AB - OBJECTIVE: To evaluate engraftment status of patients after allogeneic peripheral blood stem cell transplantation (allo-PBSCT) based on red blood cell type, karyotype and variable number of tandem repeats (VNTR). METHODS: Amplification of 3 loci of VNTR in vitro by polymerase chain reaction (PCR) was preformed to detect the polymorphism of 15 patients post-PBSCT. Furthermore, analysis of karyotype in 7 sex-mismatched patients and red blood cell antigen switching in 3 ABO blood type mismatched patients were also employed. RESULTS: VNTR analysis in 15 patients revealed complete chimerism in 11 patients and mixed chimerism in 4. In the 7 sex-mismatched patients, karyotype analysis showed types of their donors. As for blood type analysis, it was after 2 months that the first patient transformed to his donor's type. One patient showed mixed status 7 months after transplantation. CONCLUSION: Amplification of VNTR loci by PCR for documenting engraftment status after allo-PBSCT is simple and sensitive. This technology is especially suitable for patients who have received stem cells with the same sex, same blood type and identical HLA type. Examination with several different VNTR loci will improve the power of discrimination. PMID- 11218876 TI - [Histological and ultrastructural characteristics of interface membrane around aseptically loosened prostheses]. AB - OBJECTIVE: To investigate the effect of wear particles on prosthetic loosening by analyzing the histological and ultrastructural characteristics of interface membrane around aseptically loosened prostheses. METHODS: Slices of interface membranes around aseptically loosened hip prostheses of 51 cases were stained with HE, Safranin O-Briliant green and CD68 Mab immunohistochemical technique respectively. The histological structure of the membranes and the kinds of wear particles and their distribution characters were observed. The size of particles and the number of CD68 positive cells were measured. Ultrastructure of cells in the membrane and the characters and size of the particles phagocytozed by M phi were also observed and measured. RESULTS: Interface membrane consisted of fibromatrix, fibroblasts, M phi[CD68 positive, occupying (23 +/- 5)% (x +/- s)], and foreign body giant cells. In the membranes at the site of osteolysis, great amount of UHMWPE particles, PMMA particles and Ti alloy or CoCr alloy particles collected at the side attaching to the implant and caused chronic foreign body inflammatory reaction. Most of the particles outside M phi were less than 15 microns while that inside M phi were less than 1 micron. Different kinds of wear particles could exist in the lysosomes of one M phi. No particles but cartilage like tisses appeared in the membranes at the site without osteolysis. CONCLUSION: Wear particles in the interface membrane have relations with osteolysis and fibrous tissue proliferation at bone-implant interface, which plays an important role in aseptic loosening. PMID- 11218877 TI - [The expression of platelet-derived endothelial cell growth factor in liver cancer]. AB - OBJECTIVE: To investigate the expression of platelet-derived endothelial cell growth factor (PD-ECGF) in liver cancer and explore its related intervention with Capecitabine for the growth and metastasis of liver cancer. METHODS: The protein level of PD-ECGF was determined using immunohistochemical method in 61 HCC samples and the mRNA level was detected using Northern blot analysis. Capecitabine was administered orally in 24 nude mice bearing LCI-D20 tumor. All treatments lasted 3 weeks. The tumor size was calculated by the following formula: V = a x b2 x 0.5. Lung metastasis was evaluated by HE staining in lung samples. RESULTS: The PD-ECGF expression rate in 61 HCC and paratumoral liver tissues was 70.5% and 47.5%, respectively. The rate was higher in HCC tissues with advanced TNM stage than in those with early TNM stage (81.1% vs 54.2%, P < 0.05). The mRNA level of PD-ECGF was related well to its protein expression. The tumor size on day 3 after last treatment measured in the control, and low dose (1.05 mmol.kg-1.day-1), moderate dose (2.10 mmol.kg-1.day-1) and high dose (3.15 mmol.kg-1.day-1) of Capecitabine treatment groups was 447 mm3 +/- 159 mm3, 414 mm3 +/- 97 mm3, 240 mm3 +/- 119 mm3 and 209 mm3 +/- 150 mm3, respectively. High doses of Capecitabine increased the inhibitory effect on the growth and lung metastasis of HCC implant. CONCLUSION: PD-ECGF is highly expressed in HCC and correlates with the TNM staging. Capecitabine may inhibit the growth and metastasis of HCC. PMID- 11218878 TI - [Prospective study on the relationship between treatment duration of antithyroid drug and remission rate of Graves' disease]. AB - OBJECTIVE: To compare the potential benefits of 36-month treatment with 6- and 18 month treatment of antithyroid drug in patients with hyperthyroidism due to Graves' disease (GD). METHODS: 183 GD patients were studied prospectively. All patients received methimazole (MMI) at decreasing doses for 6, 18 or 36 months. The relapse rates 18 months after MMI withdrawal were compared between the three therapy groups. RESULTS: The relapse rate 18 months after the discontinuation of treatment was higher in patients treated for 6 months than in those treated for 18 or 36 months. There was no significant difference between 18-month and 36 month treatment groups. At the end of therapy, serum thyroid stimulating antibody (TSAB) and TSH receptor antibody (TRAB) titers were greater in patents treated for 6 months (320 +/- 191 for TSAB and 8.72 +/- 5.23 for TRAB) and 18 months (165 +/- 87 and 4.55 +/- 4.17) than in those treated for 36 months (126 +/- 77 and 2.19 +/- 2.64), but no statistical difference was found between the three groups before MMI treatment. TSAB and TRAB titers were higher in patients who relapsed after discontinuation of MMI (287 +/- 94 and 6.14 +/- 2.37, respectively) compared with those who remained euthyroid through the 18-month follow-up period (144 +/- 61 and 1.97 +/- 1.06). CONCLUSIONS: Negative TSAB or TRAB at the end of antithyroid therapy is a good indicator for a long-term remission after treatment withdrawal. However, treatment duration greater than 18 months does not improve remission rate of GD. PMID- 11218879 TI - [Genetic polymorphism analysis of apoE intron 1 enhancer in patients with coronary heart disease and the association with serum lipid level]. AB - OBJECTIVE: To investigate the association between the polymorphism of apolipoprotein E (apoE) intron 1 enhancer (IE1) and the level of serum lipid in patients with coronary heart disease (CHD). METHODS: ApoE IE1 genotypes of 81 patients with CHD and 108 healthy subjects were detected by polymerase chain reaction and restriction fragment length polymorphism. RESULTS: The frequency of G/G genotype in patients with CHD was significantly higher than that in control group (P < 0.05). The frequency of G allele was significantly higher in patients than in control group (P < 0.05). The gene polymorphism of apoE IE1 obviously influenced the serum lipid levels. The concentrations of TC, and LDL-C among different genotype groups were significantly different, and the level in G/G group was higher than that in C/C group (P < 0.05). CONCLUSION: ApoE IE1 gene polymorphism is closely related to serum lipid, and G/G genotype of apoE IE1 may be a risk factor of coronary heart disease in Han Chinese. PMID- 11218880 TI - [Selected CD34+ cells transplantation: a primary clinical report]. AB - OBJECTIVE: CD34+ is an immunophenotype of hematopoietic stem cells/progenitors. CD34+ cells selection in vitro may deplete T-cells 4-5 logs and tumor cells 3-4 logs. It will benefit to mismatched related donor allo-transplantation and autologous transplantation of tumor diseases. METHODS: 19 patients aged 29 (5-52) years were treated by allo- (n = 5) or auto-PB CD34+ cells transplantation (n = 14). Grafts from fifteen patients with various disorders (3 lymphomas, 6 multiple myelomas, 2 SLE, 1 Sjogren's syndrome, 2 breast cancer and 1 medulloblastoma) and five haploidentical donors for leukemia patients (1 ALL-CR2, 2 AML-rel, 1 CML-CP and 1 MDS-RAEB) were isolated using magnetic-activated cell sorting (CliniMACS, Milteny Biotech, Germany). RESULTS: After separation, purity of CD34+ cells was > 97%. Depletion of CD34 negative cells was extensive: CD3+ 2.6-4.6 logs, CD4+ > 5 logs, CD8+ 4.6-> 5 logs, and CD19+ 1.2-3.1 logs. 19 patients who received selected CD34+ cells transplantation (CD34+ CT) were followed up for 11(1-20) months. Overall survival(OS) was 13/19 (68.4%) cases. 1/5 patients with haploidentical transplant had disease free survival for 19 months. 12/14(85.7%) auto-CD34+ CT achieved overall survival(OS). CONCLUSION: Selected CD34+ cells transplantation significantly decreases the incidence of > II GVHD and depletes tumor cell contamination. This approach may be useful to haploidentical or unrelated donor transplantation. It also benefits autologous transplant in various tumor disorders. PMID- 11218883 TI - [Diagnosis and treatment of neoplasms involving the cranio-orbital region]. AB - OBJECTIVE: To study the diagnosis and microneurosurgical treatment of neoplasms involving the cranio-orbital region. METHODS: Clinical manifestations, neuroradiological features, operative technique and postoperative complications in 16 cases of cranio-orbital region neoplasms were reviewed. RESULTS: Total resection was achieved in 5 cases, and subtotal resection in 8 cases. No operative death was observed. CONCLUSION: The neoplasms involving the cranio orbital region are uncommon. Total resection is difficult in most cases. Postoperative complications are severe and should be avoided if possible. PMID- 11218882 TI - [Influence of mannitol on early enlargement of hematoma in hypertensive cerebral hemorrhage]. AB - OBJECTIVE: To probe into the influence of mannitol on early enlargement of hematoma in hypertensive cerebral hemorrhage, and to discuss how to use mannitol correctly. METHODS: 93 patients with hypertensive supratentorial non-thalamic cerebral hemorrhage and light intracranial hypertension, and with less than 30 ml of hematoma volume determined by cranial CT within 6 h after the onset were randomly divided into a group in which mannitol was used (n = 46) or a group in which mannitol was not used (n = 47) within 24 h. Cranial CT was redone at 48 h. If the volume of hematoma increased by 33%, it was named early enlargement of hematoma. The influence of using mannitol within 24 h after the onset on early enlargement of hematoma was analyzed. RESULTS: 14(14/46) patients in the group in which mannitol was used within 24 h after the onset had early enlargement of hematoma, yet 4(4/47) patients in the group without mannitol had hematoma enlargement. There was significant difference between them (P < 0.01). No significant difference was seen between the integral of nerve function defect in the two groups when CT was done at the first time (P > 0.05). When CT was redone, the integral of nerve function defect in the group with mannitol used within 24 h was markedly higher than that in the group without mannitol (P < 0.05). 5(5/46) patients died in the former group and 1(1/47) in the latter. CONCLUSION: Improper use of mannitol within 24 h after the onset may increase the incidence of early enlargement of hematoma in patients with hypertensive cerebral hemorrhage, and exacerbate the patient's condition. For patients with hypertensive cerebral hemorrhage with light intracranial hypertension, especialy those within 24 h after the onset, mannitol should not be used blindly, in case that it enlarges the hematoma and exacerbates patient's condition. PMID- 11218881 TI - [Signal transduction and biological function of IL-6 in a human myeloma cell line XG-7]. AB - OBJECTIVE: To investigate the relationship between IL-6 signal transduction and its biological function on a human IL-6-dependent myeloma cell line-XG-7. METHODS: Electrophoretic mobility shift (EMSA) and immunopeipitation were used respectively to detect the activation of transcription factors (STAT3 and NF-IL 6) and protein kinases (JAK1 and ERK) in the two IL-6 signal transduction pathways by IL-6 in XG-7 cells. Then the cells were transfected with the sense or anti-sense expression plasmids of the transcription factors, which could up- or down-regulate the activation of the signal transduction pathways specially, the changes of the biological function of IL-6 on XG-7 cells was shown by cell number counting and MTT. RESULTS: IL-6 can promote the proliferation of XG-7 cells and activate one of the IL-6 signal transduction pathway-Ras/NF-IL-6; but Jak/STAT signal transduction pathway was not activated at the same conditions. When the activation of Ras/NF-IL-6 pathway was up- or down-regulated, the growth effect of IL-6 on XG-7 cells was strongthened or weakened. CONCLUSIONS: The proliferation of XG-7 cells in the presence of IL-6 is mediated by the activation of Ras/NF-IL 6 signal transduction pathway. PMID- 11218884 TI - [The expression of CD15 mRNA CD44v6 mRNA and nm23H1 mRNA in breast cancer and their clinical significance]. AB - OBJECTIVE: To study the relationship of the expression of CD15 mRNA and its protein, CD44v6 mRNA and nm23H1 mRNA with the clinical pathology parameter and prognosis of breast cancer, and to investigate the correlation of the expression of CD15 mRNA with CD44v6 mRNA and nm23H1 mRNA. METHODS: Catalyzed signal amplification (CSA) method of in situ hybridization and immunohistochemistry were used to detect the expression of CD15 mRNA and its protein, CD44v6 mRNA and nm23H1 mRNA in 94 cases of breast cancer. RESULTS: The overexpression of CD15 mRNA and its protein and CD44v6 mRNA and the low expression nm23H1 mRNA were correlated with the grading, clinical stage, lymph node metastasis, recurrence and prognosis of breast cancer. Patients who had overexpression of CD15 mRNA and CD44v6 mRNA and low expression of nm23H1 mRNA had a higher lymph node metastatic rate and a lower survival rate. CONCLUSION: The expression of CD15 mRNA has a synergistic action in positive and negative regulation with that of CD44v6 mRNA and nm23H1 mRNA. Combining detection of the expression of these three mRNA is a reliable index to evaluate the metastasis, recurrence and prognosis of breast cancer. PMID- 11218885 TI - [Inhibition of human glioma growth in nude mice by local secretion of angiostatin K(1-3)]. AB - OBJECTIVE: To discuss the feasibility of human glioma therapy by the local secretion of angiostatin K(1-3)[AK(1-3)]. METHOD: AK(1-3) cDNA with secretive signal was inserted into polylinker sites of eukaryotic expression vector pcDNA3 to construct pcDNA-SAK(1-3); The vector was transfected into human glioma SHG44 cells by lipofectamine and the positive clone was screened by G418. The biological characters of glioma cells were examined with electron microscopy and FCM. The activity of AK(1-3) protein expressed by the SHG44 cells was examined by the endotheliocyte inhibition assay and immunofluorescence assay. When the tumor cells were implanted into nude mice, the tumor necrosis and micrangium was calculated by immunohistochemistry and electron microscopy in order to determine the influence of AK(1-3) protein to the human glioma growth. RESULTS: The pcDNA SAK(1-3) vector was successfully constructed and transfected into glioma cells that could express AK(1-3) protein. The tumorigenesis and angiogenesis of glioma cells in nude mice were greatly reduced (tumour end volume, experiment group 170 mm3, control group 8 120 mm3, P < 0.01; Blood vessel counting, experimental group 5.4, control group 12.2, P < 0.01). CONCLUSION: The human glioma angiogenesis and growth were inhibited by the local secretion of AK(1-3). It can be further used in the treatment of other solid tumors. PMID- 11218887 TI - [Study on COL7A1 gene mutation in a epidermolysis bullosa pruriginosa family]. AB - OBJECTIVE: To identify gene mutation of a epidermolysis bullosa pruriginosa family. METHODS: Polymerase chain reaction (PCR), DNA sequencing, multiplex PCR using allele-specific oligonucleotide primers. RESULTS: A G6100A transition of COL7A1 was found in patients, resulting in G2034R substitution in type VII collagen. The mutation was not found in control normal individuals. CONCLUSION: The mutation of G2034R is the underlying cause of epidermolysis bullosa pruriginosa in this family, not common polymorphism. PMID- 11218886 TI - [A study of human breast carcinoma xenografts in nude mice]. AB - OBJECTIVE: To study the spontaneous metastasis and the genetic stability of human breast carcinoma xenografts in nude mice and its micrometastasis. METHODS: The intact tissue of surgical specimens from breast carcinoma were xenografted into nude mice and transplanted from generation to generation. Cells from the xenografts were cultured in vitro and retransplanted into nude mice. Microsatellite DNA in genome of human breast carcinoma, xenotransplanted tumors and metastases in nude mice were analysed at three microsatellite loci. RESULTS: The tumorigenicity of orthotopic xenotransplantation was 88.6%(31/35) with a metastasis rate of 41.9%(13/31). Cells from the xenografts were cultured in vitro successfully, both the take rate of retransplantation into nude mice and the spontaneous lung metastasis rate were 100%(10/10). Microsatellite DNA sequences in genome of the xenotransplanted tumors and metastases in nude mice were identical with that of the original human breast carcinoma at the three microsatellite loci. CONCLUSIONS: The tumorigenicity and metastasis potential can be improved in human breast carcinoma xenograft using the intact fresh tumor tissue and orthotopic graft. The xenotransplanted tumors and their passaged tumors maintained the genetic stability. The detection of microsatellite DNA may discover micrometastasis in the nude mice model. PMID- 11218888 TI - [Neutrophil activation in pathogenesis of preeclampsia]. AB - OBJECTIVE: To investigate the effect of neutrophil activation on pathogenesis of preeclampsia. METHODS: In 22 pregnant women with preeclampsia and 21 normal pregnant women at third trimester, neutrophil activation was examined by flow cytometry to assess the CD11b expression, and the levels of plasma endothelin-1 (ET-1) and serum NO2- were also measured with no-equilibrium radio-immunoassay and with Griess assay respectively. RESULTS: The expression of neutrophil CD11b was significantly elevated in women with preeclampsia compared with that of normal pregnant women at third trimester [the mean fluorescence index of CD11b were 439.1 +/- 169.1 and 321.2 +/- 166.3 respectively, P < 0.05], the plasma ET-1 level and serum NO2- concentration in preeclampsic women [(61.4 +/- 48.2) ng/L and (20.4 +/- 5.2) mumol/L, respectively] were both significantly increased compared with those in the normal pregnancy women [(29.3 +/- 20.9) ng/L and (15.5 +/- 4.8) mumol/L, respectively], (P < 0.01). The mean fluorescence index of CD11b was significantly correlated with plasma ET-1 level and serum NO2- concentration (r = 0.312 and 0.382, respectively, P < 0.05). But the correlation between the plasma ET-1 level and serum NO2- concentration was not found (r = 0.227, P > 0.05). CONCLUSIONS: The neutrophil CD11b expression is significantly elevated in preeclampsia. The increased neutrophil activation may cause the damage of vascular endothelium and result in compensatory increase of NO release in endothelial cells. It suggests that the neutrophil activation may play a key role in pathogenesis of preeclampsia. PMID- 11218889 TI - [Clinical significance of beta-hCG and human placental lactogen in serum of normal pregnancies and patients with pregnancy induced hypertension]. AB - OBJECTIVE: To examine the level of beta-hCG and Human Placental Lactogen (HPL) in maternal serum of normal pregnancies and patients with pregnancy induced hypertension (PIH) and to study the clinical significance and effects of them on the pathogenesis of the disease. METHODS: Serum levels of beta-hCG and HPL of 142 normal pregnant women and 43 patients with PIH (16 mild, 12 moderate and 15 severe) were determined by radioimmunossay. RESULTS: (1) Serum levels of beta-hCG in all PIH subgroups [(25.33 +/- 17.80) micrograms/L in mild, (33.12 +/- 4.91) micrograms/L in moderate, (42.19 +/- 17.47) micrograms/L in severe] were significantly higher than the normal pregnant group [(12.33 +/- 7.92) micrograms/L; P < 0.001]. There is positive correlation between levels of beta hCG and degrees of PIH (r = 0.677, P < 0.05). (2) Serum levels of HPL in all PIH subgroups [(14.73 +/- 3.26) mg/L in mild, (11.44 +/- 4.02) mg/L in moderate, (12.73 +/- 4.18) mg/L in severe] did not show significant difference when compared with that of normal pregnant group [(12.78 +/- 4.67) mg/L; P > 0.05]. Furthermore, there was no correlation between levels of HPL and degrees of PIH (r = -0.300, P > 0.05). CONCLUSIONS: Serum beta-hCG could reflect the degree of functional imbalance of the placental trophoblasts on PIH and it may be used as a clinical detecting index of PIH. On the other hand, HPL is not such a useful factor. PMID- 11218890 TI - [Clinical study on morphological characteristics of placenta in severe pregnancy induced hypertension]. AB - OBJECTIVE: To study morphological characteristics of placenta in severe pregnancy induced hypertension (SPIH) and its relationship to pregnant outcome. METHODS: Morphological changes were observed by light microscopy; Blood biochemical analyses were used to predispose pregnant outcome. RESULTS: Difference in pathological changes of placental bed between normal term pregnancy (NTP) and SPIH groups was significant: the placental weight, proliferation of cytotrophoblasts, numbers of the placental villi with syncytial knots, thickness of basal lamina, fibrinoid necrosis and deposition of matrix, stromal edema and fibrosis of villi, the vascular numbers of villi, stasis; lack of physiologic changes in decidual spiral arteries. Clinical examination showed that the rate of anemia, thrombocytopenia, blood concentration, hypoproteinemia, ascites, eye ground artery spasm in SPIH were higher in NIT. CONCLUSIONS: Pathological changes of placenta play important roles in development of SPIH, and the pathological changes are paralleled with the severity of the disease. PMID- 11218891 TI - [Study on hepatitis B virus infection status in placentas of hepatitis B surface antigen positive pregnant women during middle and late period of pregnancy]. AB - OBJECTIVE: To investigate Hepatitis B Virus (HBV) infection status in placentas of Hepatitis B Surface Antigen (HBsAg) positive pregnant women during middle and late period of pregnancy. METHODS: One hundred and sixty-seven placentas from HBsAg positive pregnant women were collected, including 158 term placentas and 9 aborted second-trimester placentas. HBsAg and hepatitis B core antibody (HBcAg) in placental cytotypes were detected by immunohistochemistry. RESULTS: Of the 158 term placentas, HBV infection rates in decidual cells (DC), trophoblastic cells (TC), villous mesenchymal cells (VMC) and villous capillary endothelial cells (VCEC) were 66.46% (105/158), 58.23% (92/158), 27.22% (43/158) and 12.66% (20/158), respectively. The HBV infection rates gradually decreased from maternal side to fetal side of placentas. Both HBsAg and HBcAg were mainly located in the cytoplasm of infected cells. The positive cells were mostly in focal distribution. One out of 9 aborted second-trimester placentas was infected. CONCLUSIONS: HBV infection was found in different cells of term placentas. The positive rates for HBsAg and HBcAg in placentas were gradually decreased from maternal side to fetal side. The positive rate was low in aborted second trimester placentas. PMID- 11218892 TI - [Effects of tumor necrosis factor-alpha on proliferation and intracellular free calcium concentration in endothelium of human umbilical vein endothelial cells]. AB - OBJECTIVE: To Observe the effects of tumor necrosis factor-alpha (TNF-alpha) on cell proliferation and Intracellular free calcium concentration ([Ca2+]i) in endothelium of human umbilical vein endothelial cells (HUVEC) and investigate the pathogenesis of pregnancy induced hypertension syndrome (PIH). METHODS: Confluent monolayer of HUVEC was directly incubated with TNF-alpha at following final concentrations: 500, 1,000, 2,000 U/ml for 24 hours. The percentages of different cellcycles and [Ca2+]i were measured by flow cytometry and fluorospectrophotmetry. RESULTS: Incubated with TNF-alpha, the endothelial cells were elongated and transformed into fibroblast-like cells. Border of nucleus was sharp, clarity, and cells were in regular shape. But there were abnormal granules in cytoplasma and some cells detached at the concentrotion of 2,000 U/ml of TNF alpha. Stimulated by TNF-alpha, the percentage of cellcycles from phase G0 + G1 to S and G2 + M decreased significantly and it was dose-dependent [Ca2+]i increased significantly and dose-dependent as well. CONCLUSION: TNF-alpha may injure endothelium directly and inhibit its proliferation and repair through the changes of [Ca2+]i level. It may play an important role in the pathogenesis of PIH. PMID- 11218893 TI - [Clinical study on postpartum depression and its related factors]. AB - OBJECTIVE: The prevalence rate, related factors and clinical characteristics of postpartum depression were studied in order to promote obstetrician's understanding of the disease, and resort to preventive and therapeutic measure earlier. METHODS: Two hundred and ten puerpera were selected from September to November 1998 for mood study by self-rating depression scale, self-rating anxiety scale, Hamilton depression scale, and self-made questionnaires. RESULTS: The prevalence rate of postpartum depression was 37.14% (78/210), of which, 91.03% (71/78) was mild, and 8.97% (7/78) moderate. In addition, 10.48% (22/210) of women got anxiety after delivery. The symptoms, including decreased activity, difficulty in thinking, problems in decision-making, difficulty in doing things, feeling of uselessness and hopelessness were chief complaints of postpartum depression patients. Bad social behavior and mood controlling, inadequate psychological preparation for delivery, lack of knowledge of delivery were closely correlated to the onset of postpartum depression, which are the risk factors of postpartum depression. CONCLUSIONS: Postpartum depression is a spiritual and psychological obstacle with relatively high prevalence rate. Bad social psychological factors can bring out and aggravate postpartum depression. It is important to carry out prenatal psychological care and to propagate the knowledge of delivery, to find out and cure of postpartum depression as soon as possible. PMID- 11218894 TI - [Treatment of intrauterine growth retardation with magnesium sulfate]. AB - OBJECTIVE: To study the relationship between magnesium level in umbilical vein and mother's peripheral blood with intrauterine growth retardation (IUGR) and fetal weight. METHODS: 39 pregnant women with IUGR were randomly divided into 3 groups: Group 1 (n = 14): The patients were treated with 10% glucose 500 ml + danshen compound 14 ml + low molecular weight dextran 500 ml i.v.; Group 2 (n = 14): in addition to the same treatment as in group 1, 25% magnesium sulfate 20 ml in 5% glucose 500 ml i.v. was given; Group 3 (n = 11): no treatment was given; and another 12 normal term delivery women were served as control. Magnesium concentration levels were determined in both maternal peripheral blood and their fetal umbilical vein. RESULTS: Maternal serum magnesium level was higher in Group 2 (1.06 +/- 0.09) mmol/L than that in Group 1 (0.69 +/- 0.05) mmol/L (P < 0.05), while there was no significant difference between Group 1 and Group 3. The serum magnesium levels in both mother and fetal umbilical vein of normal pregnancy and of Group 2 were significantly higher than those of Group 1 and 3 (P < 0.01), so did the birth weight of their newborns (P < 0.05). CONCLUSION: Magnesium deficiency might be one of the causes of IUGR, and magnesium sulfate treatment was effective. PMID- 11218895 TI - [Clinical analysis of 25 cases of malignant transformation of endometriosis of the ovary]. AB - OBJECTIVE: To study clinicopathologic characteristics, treatment and prognostic factors of malignant transformation of endometriosis of the ovary. METHODS: From 1981 to 1999, a total of 25 patients with malignant transformation of endometriosis of the ovary were retrospectively analyzed. RESULTS: The main symptoms were pelvic masses, abdominal pain, abdominal distension and abnormal vaginal bleeding or discharge. Histological type: of the 25 cases, 14 were endometrioid carcinomas, 2 were clear-cell carcinomas, 2 were adenoacanthoma, 1 was serous papillary adenocarcinomas, 6 were mixed epithelium tumor of ovary. The exact area of histologic transition from benign to malignant epithelium was observed in 25 patients. Stage: stage I 14, stage II 7, stage III 3, stage IV 1. The actual 5-year survival rate was 77.7%. CONCLUSIONS: The exact incidence and prevalence of malignant transformation in endomertriosis is unknown. Radical tumor resection combined with chemotherapy is the main therapeutic approach for malignant transformation of endometriosis of the ovary. PMID- 11218896 TI - [Expression of vascular endothelial growth factor receptor kinase inser domain containing receptor in human cervical carcinoma]. AB - OBJECTIVE: To observe the expression of vascular endothelial growth factor receptor (KDR) in human cervical carcinomas, to clarify the relationship between the expression and invasion, metastasis, prognostic value in human cervical carcinoma. METHODS: KDR was stained immunohistochemically in 80 cases of human cervical carcinoma. RESULTS: The expression of KDR in the endothelial cells of tumor vasculature is: the high KDR expression rate of clinical cancer stages < or = I b and II a-III a was 21.4% and 60.6% (P < 0.01). The high KDR expression rate of the high, middle and low pathohistologic grading was 7.7%, 27.8% and 84.1% respectively (P < 0.01). The high KDR expression rate of adenocarcinoma and squamous-cell carcinoma was 0/5 and 57.3% (P < 0.05). The high KDR expression rate of the cases with lymphonodus metastasis and without lymphonodus metastasis was 77.8% and 46.8% respectively (P < 0.05). The survival rate of patients with high KDR expression tumors was significantly lower than that of patients with low KDR expression (P < 0.05). CONCLUSION: KDR is highly related to growth, invasion and metastasis of human cervical carcinoma, it may be one of the predictors for the biological behavior of human cervical carcinoma. PMID- 11218898 TI - [Study of mdr1 antisense oligodeoxynucleotides on reversal of multidrug resistance in ovarian carcinoma cell line SKOV3]. AB - OBJECTIVE: To investigate the effect of mdr1 antisense oligodeoxynucleotides (ASON) on reversal of multidrug resistance in ovarian carcinoma cells. METHODS: Drug resistance ovarian carcinoma cells SKOV3/mdr1 transducted with human multidrug resistance gene (mdr1) were served as models. The positive rate and function of the mdr1 gene product P-glycoprotein (P-gp) in SKOV3/mdr1 cells after mdr1-ASON (250 micrograms/ml) treatment were determined by flow cytometry and rhodamine 123 efflux trial. Drug resistance of SKOV3/mdr1 cells was also observed by cell colony culture. RESULTS: P-gp positive rate of SKOV3/mdr1 cells after mdr1-ASON treatment was decreased from 38.9% to 21.3% (P < 0.01). Intracellular rhodamine retension in SKOV3/mdr1 cells after mdr1-ASON treatment was increased from 32.1% to 50.7% (P < 0.01). Under effect of Taxol 5 ng/ml, the relative percents of drug-resistant colony in mdr1-ASON treated SKOV3/mdr1 cells and in SKOV3/mdr1 cells was 8% and 63%, respectively, (P < 0.01). Under effect of Doxorubicin 100 ng/ml, the relative percents of drug-resistant colony in mdr1 ASON treated SKOV3/mdr1 cells and in SKOV3/mdr1 cells was 34% and 79%, respectively, (P < 0.01). CONCLUSION: mdr1-ASON can reverse multidrug resistance of ovarian carcinoma cell in a certain extent so as to increase chemotherapeutic sensitivity of ovarian carcinoma cells. PMID- 11218897 TI - [Prognostic factors in granulosa cell tumor of the ovary]. AB - OBJECTIVE: To study the effect of clinical and pathologic factors on prognosis for granulosa cell tumor of the ovary. METHODS: The clinical records and tumor sections of 100 patients with granulosa cell tumors of the ovary between 1958 and 1995 were reviewed. The relationship between age, stage, mitosis and the adjuvant therapy for early stage (stage I) were analyzed retrospectively. Patients with recurrent tumors were compared with patients who remained without disease, patients with early recurring tumors were compared with late recurring tumors. RESULTS: The overall 5 and 10 year survival rates were 80% and 72%. There were no significant difference between ages and survival (P > 0.05). The survival rates in stage I were 98% and 96% after 5 and 10 years, respectively, and in stages II were 70% and 60%, after 5 and 10 years, all of 4 patients with stage III-IV were dead of recurrent disease in 1 year. The frequency of observed mitosis influenced the survival rate: with less 5/10 high-power fields (HPF) the survival were 96% both at 5 and 10 years, with more or equal 5/10 HPF the 5 and 10 year survival rates were 58% and 36%, respectively (P < 0.01). No significant correlation could be established between the adjuvant therapy and 5 and 10 years survival in 56 stage I patients. There were 44 patients with recurrent disease in this group, median time to recurrence was 53 months. Late recurrence appeared in 8 cases. The significant differences in stage and abdominal mass were noted between the recurrent tumors and the group without disease (P < 0.05). When early and late recurring tumors were compared, statistically significant differences were again noted: early recurring tumors had higher mitotic rates and late stage, and late recurring tumors had lower mitotic rages and early stage. Patients without recurrent tumors were similar to the patients with early recurring tumors. CONCLUSIONS: Tumor stage and mitotic rate are the clinical and pathologic prognosticators in granulosa cell tumor. It is difficult to predict late recurrences using these clinical and pathologic parameters. PMID- 11218899 TI - [Long-term effects of low-dose combined norethisterone and combined 18-metayl norethisterone on lipid metabolism in healthy women]. AB - OBJECTIVE: To assess the long-term effects of combined oral contraceptive pills use on the mean of serum TG, TC, HDL-C, LDL-C, ApoA1, ApoB and Lp(a). METHODS: The study was carried out in 446 women grouped as combined norethisterone containing ethinylestradiol (EE) 35 micrograms and norethisterone 625 micrograms; combined 18-metayl-norethisterone (norgestrel) containing EE 30 micrograms and 18 metayl-norethisterone 300 micrograms for using 5-25 years, and control subjects wearing IUD for the corresponding period. The three groups were similar in age, body mass index (BMI), continued period of contraceptives use and income. RESULTS: The data showed that changes of varying degree of lipid and lipoprotein parameters were obvious in women of long-term taking low-dose combined norethisterone and norgestrel, compared with the control. The mean of TG, HDL-C, ApoA1 were significantly increased simultaneously (P < 0.05, P < 0.01), indicated multiple effects of two low-dose Chinese COCs on lipid lipoprotein parameters. In addition, A significant increase (P < 0.05) in Lp(a), an independent risk factor for cardiovascular disease, was found in norgestrel group. Further more, the results of stratified analysis to duration of contraceptives use showed that the mean of TC, LDL-C, in the combined norethisterone use less than 15 years, after the adjusting for age, were significantly lower (P < 0.05, P < 0.01) and the ratio of LDL-C/HDL-C was improved (P < 0.05), compared with the Norgestrel; at the same time, the mean of ApoA1 was markedly higher (P < 0.05) in combined norethisterone; the ratio of ApoA1/ApoB (1.87 +/- 0.58) in the combined norethisterone group was superior to the ratio value (1.68 +/- 0.55) in norgestrel group. CONCLUSIONS: These beneficial effects on lipid metabolism have been considered indicators of potential cardiovascular protective effect of the combined norethisterone for taking pill less than 15 years, but these protective effects would be reduced with adverse change in lipid and lipoprotein parameters for taking combined norethisterone more than 15 years. In contrast, the mean of TC, LDL-C, two known risk factors for cardiovascular system, in the norgestrel use less than 15 years, after the adjusting for age, were significantly increased (P < 0.05, P < 0.01), and adverse changes in the TC/HDL-C ratio (P < 0.05) and ASI value, compared with the combined norethisterone; Lp(a) level was markedly higher in the norgestrel group than that in the control group (P < 0.05). These adverse effects on lipid metabolism have been considered indicators of potential cardiovascular harmful effect of low-dose norgestrel. PMID- 11218900 TI - Joint Commission improves accreditation process. PMID- 11218901 TI - Maintain a high census, or "how to keep your beds filled". PMID- 11218902 TI - Assisted living comes of age: a bright future lies ahead for the popular senior care alternative. PMID- 11218903 TI - Healthcare facilities must act affirmatively to prevent sexual harassment. PMID- 11218904 TI - Illinois nursing homes develop successful programs to promote comfort during end of-life care. PMID- 11218905 TI - Celebrate long-term care administrators week. March 19-25, 2001. PMID- 11218906 TI - Twenty ways to motivate yourself. PMID- 11218907 TI - Congress fixes Medicare reimbursement rate glitches. PMID- 11218908 TI - Taking stock of the eldercare market. PMID- 11218909 TI - Benign tumors of the liver. AB - Benign tumors of the liver, less commonly encountered than metastatic or primary liver tumors, may present clinically with symptoms due to mass effect, or may be discovered incidentally during radiographic evaluation or surgical exploration for other clinical indications. Many of the lesions that result in a benign liver mass are true neoplasms, while others result from reactive proliferation of hepatocytes, biliary cells, mesenchymal or inflammatory cells. The premalignant nature or potential for malignant transformation is of concern in some of the benign tumors or tumor-like masses of the liver. In this article, benign tumors and tumor-like masses involving the adult liver are discussed with a focus on histopathology, histogenesis, and clinical significance of these interesting and unusual lesions. PMID- 11218910 TI - Screening for cancer in viral hepatitis. AB - Early diagnosis of HCC is possible because certain risk factors for this tumor are known and because sensitive and relatively inexpensive diagnostic tools are available. Early diagnosis of HCC is also possible because of the long phase of asymptomatic tumor growth and the tumor's tendency to grow as a solitary mass in many patients. In two consensus development conferences held in Anchorage, Alaska and in Milan, Italy, chronic carriers of HBsAg, patients with cirrhosis, patients with rare metabolic liver diseases, and individuals with family histories of HCC were identified as patients at high risk for HCC and therefore as candidates for periodic screening. At the Anchorage conference, it was recommended that healthy carriers have at least yearly determinations of serum AFP and that carriers with additional risk factors (e.g., cirrhosis) be screened every 6 months by abdominal US scans and determination of serum AFP levels. No specific recommendations were released for HBsAg-negative patients with chronic liver disease. At the Milan conference, it was recommend that patients with cirrhosis or with certain congenital metabolic conditions known to be at risk for HCC should be screened by AFP determination and US scan twice a year. It was also recommended that HBsAg carriers older than 35 years or with family histories of HCC should be screened for HCC by determinations of serum AFP levels and aminotransferase levels once a year. PMID- 11218911 TI - Radiologic diagnosis of hepatocellular carcinoma. AB - Substantial recent technologic improvements in CT scanning, US scanning, and MR imaging, together with advances in the understanding of the optimal application of contrast administration techniques, have facilitated advances in radiologic imaging detection for HCC diagnosis. Despite a large number of earlier publications reporting a high sensitivity for imaging detection of HCC, more recent screening studies of large cirrhotic populations confirm that only 37% to 45% of HCC tumor nodules are detected by CT scanning, US scanning, or MR imaging. Future investigation will include efforts to improve the detection of small tumors and to characterize with greater specificity the spectrum of nodular changes that occur with cirrhosis. Although several small series have attempted to characterize cirrhotic nodules by evaluating the relative arterial or portal blood supply, these preliminary results require substantiation with larger series. Continued technologic advances such as multidetector helical CT scanning and new US and MR contrast agents under investigation may improve the imaging characterization of cirrhotic nodules. PMID- 11218912 TI - The role of serum alpha-fetoprotein estimation in the diagnosis and management of hepatocellular carcinoma. AB - Forty years after its discovery, estimation of serum AFP remains a useful test for clinicians involved in management of patients with HCC or chronic liver disease. The test, when used with the conventional cut-off point of 500 ng/mL, has a sensitivity of about 50% and a specificity of more than 90% in detecting the presence of HCC in a patient with coexisting liver disease. New tests that can significantly increase the specificity at lower levels (i.e., between 10 and 500 ng/mL) are available but have, to date, been too complex to be widely applied in clinical practice. Serum AFP estimation may also be useful in monitoring response to therapy, particularly as more effective systemic regimens are becoming available. Indeed, there is preliminary evidence that changes in serum AFP may be a more accurate and sensitive way of determining the degree of response to treatment than conventional imaging procedures that rely on physical determination of tumor size. It may, perhaps, be time to add changes in serum AFP to the conventional imaging criteria for assessing response in clinical trials. PMID- 11218913 TI - Locoregional management of hepatocellular carcinoma. Surgical and ablation therapies. AB - The selection of an appropriate treatment strategy for patients with HCC depends on careful tumor staging and assessment of the underlying liver disease (Fig. 5). All patients with localized HCC (involvement of one single lobe, no vascular invasion or extrahepatic disease) should be evaluated for the potentially curative therapeutic options of partial hepatectomy or OLT. Candidates for partial hepatectomy must have no liver disease or Child's A cirrhosis, normal portal pressure, and normal serum bilirubin. For patients not meeting these criteria, OLT should be considered if there is a solitary lesion smaller than 5 cm in diameter or fewer than three lesions smaller than 3 cm. Local ablative therapies such as PEI, RFA, and TACE offer palliation for patients for whom surgical approaches are contraindicated. Percutaneous alcohol injection and RFA are minimally invasive and can be used on an outpatient basis, usually for tumor nodules smaller than 3 cm. When these therapies are used for small tumors, the survival rates can be similar to those achieved by partial hepatectomy. Transcatheter [figure: see text] arterial chemoembolization may be used as an interim treatment for patients waiting for OLT. Although TACE is often used for the palliation of large tumors, significant survival benefits have not yet been demonstrated for this indication. PMID- 11218914 TI - Benign focal lesions of the liver. AB - This article focuses on the origin, diagnosis, and management of focal benign lesions of the liver. The most common lesions include cavernous hemangioma, focal nodular hyperplasia, hepatic adenoma, and nodular regenerative hyperplasia. A number of less frequent occurring lesions are also discussed. In general, the common lesions can be diagnosed by radiologic imaging, but occasionally biopsies are required, and surgical removal is often needed. PMID- 11218915 TI - Nonsurgical treatment of hepatocellular carcinoma. AB - Given the poor prognosis of HCC and the therapeutic challenge posed by underlying liver cirrhosis, efforts and resources must be directed towards preventive strategies. Return on the investment in such research is likely to be greater than can be expected from treatment of advanced disease. PMID- 11218916 TI - Cholangiocarcinoma. AB - Despite overall advances in the ability to diagnose and treat patients with cholangiocarcinoma, the prognosis for patients with this malignancy remains poor. Further improvements in the survival of patients with cholangiocarcinoma will come with the early diagnosis of these lesions. New molecular techniques should improve the ability to screen high-risk patients, such as those with primary sclerosing cholangitis, hepatolithiasis, choledochal cysts, and ulcerative colitis. Improvements in imaging will continue, and spiral CT scanning, duplex ultrasonography, MR imaging and, perhaps, PET scans will improve the ability to stage patients with cholangiocarcinoma noninvasively. Complete surgical resection remains the only curative treatment for malignancies of the biliary tract. Aggressive surgical approaches are likely to continue, and the challenge remains in being able to perform these procedures safely in jaundiced and sometimes septic patients. For patients with unresectable lesions, the optimal form of palliation, whether surgical or nonsurgical, remains to be defined. Finally, multicenter, prospective, randomized trials of chemoradiation need to be performed to delineate an effective adjuvant therapy more precisely, and to improve the overall prognosis of patients with cholangiocarcinoma. PMID- 11218917 TI - Mesenchymal tumors of the liver. AB - Primary angiosarcoma of the liver accounts for up to 2% of all primary liver tumors and is the second most common primary malignant neoplasm of the liver. Approximately 10 to 20 new cases are diagnosed every year in the United States and the prevalence varies from 0.14 to 0.25 per million. In an autopsy series from Chicago, one hepatic angiosarcoma was noted for every 30 cases of hepatocellular carcinoma. PMID- 11218918 TI - Hepatic tumors in children. AB - Although they account for only 1% to 4% of solid tumors in children, hepatic tumors and pseudotumors offer a diagnostic challenge to the clinician seeing only an occasional case. Metastatic lesions such as neuroblastoma, Wilms' tumor, and lymphoma are the most common neoplasm seen in the liver, but 10 distinct primary tumors and pseudotumors of the liver occur with some regularity, and a few others may be seen rarely, including leiomyosarcoma, rhabdoid tumor, and endodermal sinus tumor. Five of these neoplasms--hepatoblastoma, infantile hemangio endothelioma, mesenchymal hamartoma, undifferentiated embryonal sarcoma, and embryonal rhabdomyosarcoma of the biliary tree--occur only in children and are the major focus of the article. PMID- 11218919 TI - Animal models of hepadnavirus-associated hepatocellular carcinoma. AB - Animal models of hepatitis B virus infection have been valuable for determining the mechanisms of hepadnavirus replication, for studies of pathogenesis, and for investigations of viral hepatocarcinogenesis. The woodchuck model also seems to be useful in the discovery and development of antiviral drugs to treat HBV infection and for testing new forms of immunotherapy. In particular, the woodchuck seems to be ideal for studying the effect of antiviral treatment and immunotherapy on the outcome of hepadnavirus infection and on survival. The median life expectancy of experimentally infected, chronic WHV carriers is approximately 29 months, and almost all develop HCC. New types of prophylaxis or therapy can be evaluated under controlled experimental conditions, in a relevant animal model, and within a reasonable time frame. PMID- 11218920 TI - Pathogenesis of hepatocellular carcinoma. AB - The pathogenesis of HCC is poorly understood at present. There is insufficient understanding to propose a robust general model of hepatic carcinogenesis, partly because pathogenic host and environmental factors show significant regional variation, making such generalization difficult. Figure 4 is a model based on data presented in this article. Multiple risk factors for HCC have been identified, including cirrhosis, male gender, increasing patient age, toxins, chronic viral hepatitis, and other specific liver diseases. The understanding of how the individual risk factors result in genetic changes is rudimentary, and there is even less understanding about interactions between risk factors. Future studies should acknowledge the geographic origin of the HCCs studied and consider the effects of cirrhosis, gender, and age. A more rigorous approach to these factors may help explicate the interaction with specific liver diseases so that a comprehensive model of hepatic carcinogenesis can be developed. PMID- 11218921 TI - Epidemiology of hepatocellular carcinoma. AB - The epidemiology of hepatocellular carcinoma (HCC) is characterized by marked differences between genders, ethnic groups, and geographic regions. These variations are explained by the nature, frequency, and time of acquisition of the major risk factors for cirrhosis--namely hepatitis B virus, hepatitis C virus (HCV), and alcoholic cirrhosis. The incidence and mortality of HCC has been rising in the US over the last two decades and is progressively affecting younger persons. The evidence indicates that HCV infection is responsible for the current trends. PMID- 11218922 TI - Influence of a scheduled-waiting task on EMG reactivity and oral habits among facial pain patients and no-pain controls. AB - Recent research has strongly implicated the role of psychological stress in the development of temporomandibular disorders (TMD). It is widely reported that oral habits (e.g., teeth grinding) probably provide a behavioral link between stress and the development of TMD symptomatology. Extrapolation of research in the field of adjunctive behavior to the TMD disorders suggests that oral behaviors may develop conjointly with fixed-time (FT) stimulus presentation. The current experiment extended previous research examining this possibility by assessing the influence of experimental stress on masseter EMG and oral habits among persons who met broadband criteria for TMD and no-pain controls. Oral habit activity was assessed via self-report questionnaire whereas masseter muscle activity was measured continuously via electromyography across four phases (Adaptation, Free Play, Scheduled-Play, Recovery). The Scheduled-Play phase was designed as a stress-reactivity task that included an FT schedule. Results indicated that, consistent with the stress-reactivity model, the Scheduled-Play phase resulted in a significant increase in masseter EMG levels relative to Free-Play and Adaptation, and that this effect was significantly larger for the TMD group relative to controls. The results suggest an adjunctive behavior effect although the effect was not specific to those with facial pain. Oral habit data showed a significant phase effect with oral habits that was significantly higher during the Scheduled-Play phase relative to Adaptation. The findings are the impetus for further study regarding the mechanisms whereby oral habits are developed and maintained despite their painful consequences. PMID- 11218923 TI - Oxygen consumption and respiration following two yoga relaxation techniques. AB - The present study was conducted to evaluate a statement in ancient yoga texts that suggests that a combination of both "calming" and "stimulating" measures may be especially helpful in reaching a state of mental equilibrium. Two yoga practices, one combining "calming and stimulating" measures (cyclic meditation) and the other, a "calming" technique (shavasan), were compared. The oxygen consumption, breath rate, and breath volume of 40 male volunteers (group mean +/- SD, 27.0 +/- 5.7 years) were assessed before and after sessions of cyclic meditation (CM) and before and after sessions of shavasan (SH). The 2 sessions (CM, SH) were 1 day apart. Cyclic meditation includes the practice of yoga postures interspersed with periods of supine relaxation. During SH the subject lies in a supine position throughout the practice. There was a significant decrease in the amount of oxygen consumed and in breath rate and an increase in breath volume after both types of sessions (2-factor ANOVA, paired t test). However, the magnitude of change on all 3 measures was greater after CM: (1) Oxygen consumption decreased 32.1% after CM compared with 10.1% after SH; (2) breath rate decreased 18.0% after CM and 15.2% after SH; and (3) breath volume increased 28.8% after CM and 15.9% after SH. These results support the idea that a combination of yoga postures interspersed with relaxation reduces arousal more than relaxation alone does. PMID- 11218924 TI - Electromyographic (EMG) biofeedback in the comprehensive treatment of central pain and ataxic tremor following thalamic stroke. AB - Peripheral pain and ataxic tremor can appear suddenly following thalamic stroke and can significantly alter a patient's psychological, social, and physical functioning. The present paper reports the case of a 70-year-old Caucasian female who sustained an acute left posterior cerebral artery infarction involving the thalamus and left mesiotemporal regions. She subsequently developed Central Poststroke Pain and ataxic movement of her right arm and hand in addition to a significant right-side claudication. She was treated over 16 weeks (6 weeks of EMG biofeedback and 10 weeks of psychotherapy) with a combination of EMG biofeedback, progressive muscle relaxation, behavioral pain coping skills training, Forced Use Therapy, and Cognitive Behavioral Therapy 7 years after her initial cerebral accident. The case demonstrates the utility of biofeedback when combined as part of a comprehensive treatment program to address the multiple complications associated with thalamic stroke. PMID- 11218925 TI - Stress and human spirituality 2000: at the cross roads of physics and metaphysics. AB - Although stress is defined as a perceived threat, the implications of stress go well beyond physical well-being. In the words of Carl Jung, "Every crisis is a spiritual crisis." Western science, so strongly influenced by the Cartesian Principle of Reductionism, has ignored the essence and significance of human spirituality in the health and healing process. Holistic healing honors the integration, balance, and harmony of mind, body, spirit, and emotions, where the whole is greater than the sum of the parts. Stress (unresolved issues of anger and fear) chokes the human spirit, the life force of human energy, which ultimately affects the physical body. From the perspectives of both physics and metaphysics, stress is a disruption in the state of coherence between the layers of consciousness in the human energy field. The emerging paradigm of health reunites mind, body, and spirit, and considers health as a function of coherence among the energy levels of these components. PMID- 11218926 TI - Partnership contributes to the success of the AORN Journal team. PMID- 11218927 TI - Perioperative preparation of the adolescent surgical patient. AB - The perioperative preparation of adolescents for surgery provides a challenge to nurses and other health care providers because of the wide diversity in adolescents' age, physical maturation, and cognitive and psychosocial development. Perioperative issues, informed consent, and assent differ considerably depending on the age and developmental level of each adolescent. This article provides information about adolescent growth and development and approaches to managing adolescent surgical patients. PMID- 11218928 TI - Treating benign colon disorders using laparoscopic colectomy. AB - Laparoscopic bowel surgery is a recent application of minimally invasive videoscopic techniques. Understanding the anatomy and physiology of the bowel, the background of bowel disorders and their treatment, signs and symptoms of bowel disease, and the patient selection process can help perioperative nurses better care for patients diagnosed with colon polyps, diverticulitis, and inflammatory bowel disease. PMID- 11218930 TI - Implementing a nonlatex surgical glove study in the OR. AB - Sterile surgical gloves are used to protect patients and health care workers (HCWs) from infection during surgery and to shield HCWs from exposure to bloodborne pathogens. Based on increased reports of latex allergy, many HCWs now use nonlatex surgical gloves as a substitute for natural rubber gloves. Little is known, however, about the performance of nonlatex gloves in surgery. This article describes a study that currently is being performed to test the barrier performance of nonlatex surgical gloves after they have been used in surgery and to determine HCW satisfaction. To date, 12,703 latex and nonlatex gloves from all surgical services have been collected and tested for barrier quality. This article describes the project and challenges encountered by the collaborative team of perioperative staff members and nurse researchers as they collect data. PMID- 11218931 TI - A creative process for reinforcing aseptic technique practices. AB - Issues in aseptic technique challenge every perioperative practitioner. Equally challenging for educators is how to creatively present information to large groups of staff members in a way that facilitates learning. This article describes the process used to address practice issues in aseptic technique and to present educational inservice programs to a large number of staff members. Two clinical educators formed a work group comprising staff RNs and surgical technologists to address this topic. Work group members then planned and presented a two-part education session to review these issues with surgical staff members. PMID- 11218929 TI - Comparison of different regimens for surgical hand preparation. AB - Twenty surgical staff members participated in a clinical trial to compare the microbiology and skin condition of hands when using a traditional surgical scrub (TSS) with a detergent-based antiseptic containing 4% chlorhexidine gluconate (CHG) and a short application without scrub of a waterless hand preparation (HP) containing 61% ethyl alcohol, 1% CHG, and emollients. The HP was associated with less skin damage (P = .002) and lower microbial counts postscrub at days five (P = .002) and 19 (P = .02). The HP protocol had shorter contact time (HP mean [M] = 80.7 seconds; TSS M = 144.9 seconds; P < .0001), and more subjects preferred the HP regimen (P = .001). The HP performed better than the TSS, was less costly, and should be evaluated in larger trials and considered for widespread implementation. PMID- 11218932 TI - Needlestick Safety and Prevention Act. PMID- 11218933 TI - Preoperative assessment and discharge planning for older adults undergoing ambulatory surgery. AB - Based on this survey, the prevalence of chronic illness and disability in older adult patients with respect to current ambulatory surgery practices is worrisome, especially the fragmentation of patients' care as they progress from the decision to undergo procedures, to preoperative assessment, to postoperative discharge. Ambulatory surgery unit nurses, case managers, surgeons, and office staff members must work together to better optimize time and resources. As baby boomers age, the number of older adults undergoing ambulatory surgery will increase. It is essential for ASU staff members to be cognizant of the special needs of older adult patients. Timeliness, patient education, and appropriate coordination and follow-up of care are important ingredients to successfully plan care for older adult patients undergoing ambulatory surgery. Nurses can play a pivotal role in this success. PMID- 11218934 TI - Recommended practices for maintaining a sterile field. PMID- 11218935 TI - Sampling for qualitative research. PMID- 11218936 TI - Update on Medicare reimbursement for certified RN first assistants. PMID- 11218937 TI - Helping patients (and their doctor) survive retirement. PMID- 11218938 TI - Too much energy to retire. PMID- 11218939 TI - Your career guide. Winding down, bowing out. Eager to quit? Be careful what you wish for. PMID- 11218940 TI - When bad news might make patients sicker. PMID- 11218941 TI - Medicare gave you a raise. Have you noticed? PMID- 11218942 TI - Sorry, doc, your Rolex isn't deductible. PMID- 11218943 TI - Your career guide. Winding down, bowing out. Leaving practice, but not the profession. PMID- 11218944 TI - The role of free radicals, oxidative stress and antioxidant systems in diabetic vascular disease. AB - Recent experimental findings suggest that overproduction of reactive oxygen and nitrogen species (ROS/RNS), lowered antioxidant defense and alterations of enzymatic pathways in humans with poorly controlled diabetes mellitus can contribute to endothelial, vascular and neurovascular dysfunction. Over the past decade, there has been substantial interest in oxidative stress and its potential role in diabetogenesis, development of diabetic complications, atherosclerosis and associated cardiovascular disease. Consequences of oxidative stress are damage to DNA, lipids, proteins, disruption in cellular homeostasis and accumulation of damaged molecules. This review summarizes recent knowledge on the pathomechanism of ROS/RNS in vascular oxidative stress and Maillard reactions. Evidence suggests that Maillard reactions act as amplifier of oxidative damage in aging and diabetes. Furthermore, results of experimental observations with antioxidant systems and antioxidant pharmacotherapy in the treatment of diabetes mellitus are discussed. These data indicate that the targeting therapy to specific macromolecules, tissues and organs of diabetics by specific antioxidants or combined drug preparates could become a relevant adjuvant pharmacotherapy with improved glycaemic control, blood pressure control and management of dyslipidemia for the treatment or prevention of progression of micro- and macrovascular diabetic complications. Supplementation with antioxidants as a promising complementary treatment can exert beneficial effects in diabetes. Some antidiabetic drugs may have antioxidant properties independently of their main role on glycaemia control. Therapeutic potential of inhibitors of AGEs formation for delaying of diabetic complications is now intensively studied in several laboratories. Furthermore, for functional outcomes of the intervention with antioxidants is also important development of accurate and sensitive methods for early detection of oxidative damage in diabetes. (Tab. 6, Fig. 3, Ref. 117.) PMID- 11218945 TI - [Serum neopterin levels in oncology patients in intensive care]. AB - BACKGROUND: Elevated neopterin serum levels are associated with diseases that stimulate the cellular immune response. This includes viral infections, autoimmune diseases, transplant rejection and dissemination of certain types of cancer. T-helper lymphocytes and macrophages play a key role in neopterin synthesis. The degree of activation of Th1-lymphocytes is responsible for the production of interferon-gamma and interleukin-2, which stimulate neopterin production in human macrophages. DESIGN AND METHODS: We have designed a prospective observational study to assess the dynamics of serum neopterin levels in 75 oncological patients during post-surgery period. We measured serum neopterin by means of RIA method (radioimmunoassay) in 50 uncomplicated surgery patients (group A), in 15 complicated surgery patients (group B--abdominal sepsis, peritonitis, ileus) and 10 medical ICU patients (group C). Serum levels of neopterin were measured in 5 consecutive periods: before surgery, after surgery, and on the 1st, 2nd, 3rd postoperative days. RESULTS: In all groups, we observed gradual elevation of serum neopterin. The lowest values of neopterin were measured in group A in patients with uncomplicated course following surgery: 6.75 nmol/l, 7.67 nmol/l, 8.9 nmol/l, 10.82 nmol/l and 13.66 nmol/l. A significant increase in serum neopterin levels was measured in group B in patients with septic complications during perioperative period: 18.9; 23.2; 26.82; 29.53 and 27.32 nmol/l. High values of neopterin were also measured in medical ICU patients with disseminated cancer and sepsis during ICU stay: 26.1; 58.1; 28.7 and 22.5 nmol/l. We concluded that serum neopterin levels were increased during the post-surgery period. We observed a significant increase in serum neopterin in patients with severe systemic infection or sepsis or in patients with cancer progression or dissemination (more than 15-20 nmol/l). Neopterin is a simple, reliable and sensitive parameter of cell-mediated immunity, suitable for early diagnosis of viral, autoimmune and transplantant rejection diseases. Neopterin can be used also for non-specific laboratory monitoring of cancer progression and/or dissemination. (Tab. 3, Fig. 4, Ref. 7.) PMID- 11218946 TI - [Variation in the localization of NADPH-d positive neurons in the gray matter of the spinal cord in different species]. AB - The presence of NADPH-diaphorase (NADPH-d) activity was investigated in the thoracic part of rat, rabbit and pheasant spinal cords. Histochemical method for visualization of NADPH-d was used in this study. The comparison between all spinal cord regions (laminae) in three experimental species revealed marked differences. Especially in the ventral horn, the presence of NADPH-d activity was different. While the pheasant ventral horn possessed number of scattered intensively stained neurons, the rat and rabbit showed no NADPH-d activity in this region. Pericentral area (lamina X), intermediate zone (lamina VII) and dorsal horn revealed the presence of NADPH-d positive neurons in all examinated species although they differed in the distribution of NADPH-d activity. In summary, it can be suggested that the observed differences in the presence and distribution of NADPH-d activity among species may reflect their different phylogenetic development. As a consequence, different NO function in spinal cord of various species can be presumed. (Fig. 10, Ref. 28.) PMID- 11218947 TI - [Correction of measurement errors in the ELISA test]. AB - The authors followed the influence of the arrangement of measured and control samples on microtitration plate on the ELISA test results by quantitative evaluation of rabies antibodies titres in human blood serum. They performed the test under identical conditions in all microtitration plate wells. They calculated the result according to five calibration curves--four of them were obtained by different positioning of the control positive and negative sera and the fifth curve was obtained from average values. The results from the four various positional calibration curves were significantly statistically different from the average. However, the average calibration curve--obtained from four measurements--led to identical value of rabies antibodies in cases with different dilutions of sera. The authors propose to follow some principles of measured and control samples arrangement on microtitration plates in order to minimalize the errors, caused by their dishomogeneity. (Tab. 2, Fig. 3, Ref. 10.) PMID- 11218948 TI - [Diabetic angiopathy--etiopathogenesis and clinical manifestations (hypersyndrome X)]. AB - Diabetic angiopathy is a generalised systemic disease of the vascular system which afflicts both distribution vessels (diabetic macroangiopathy) and microcirculation (diabetic microangiopathy). The diabetic angiopathy, as well as other angiostenotic diseases (obliterations, obstructions, occlusions) result in one common consequence--ischaemia. This study is based on an analysis of a large group of patients (71,662 angiologic consultant examinations which took place during the 25-year period of the existence of the Comenius University Faculty Hospital). The author indicates that the clinical course of angio-organic ischaemic syndromes determined by diabetic angiopathy is multiform, remarkably severe and unfavourable. The author has suggested the term "X hypersyndrome" referring to cases with simultaneous occurrence of various pathophysiologic abnormalities and clinical units which finally increase the risk of origin and development of diabetic angiopathy. (Tab. 7, Ref. 47.) PMID- 11218949 TI - [Treatment of salivary gland tumors in the past and at the present time at the 1st and 2nd Stomatology Clinics of the Charles University Medical School in Bratislava]. AB - The retrospective study analyzes a group of 1021 patients (484 men and 537 women) with salivary gland tumours treated at the 1st and 2nd Departments of Stomatology in Bratislava within the years 1951-1996. This time period is divided into the past (1951-1980) and recent (1981-1996) periods. The trends in the diagnosis and treatment with the main emphasis on surgical procedures are mentioned. The most common operation were lateral parotidectomy (409 cases = 40.1%) and conservative parotidectomy (105 cases = 10.2%), enucleations were indicated rarely. Authors stress the necessity of team approach and cooperation of maxillofacial surgeons, radiologists, histopathologists, otorhinolaryngologists and oncologists. (Tab. 1, Fig. 2, Ref. 6.) PMID- 11218950 TI - [Diabetic nephropathy: new findings on pathogenesis and therapy]. AB - The authors describe the new factors (genetic, haemodynamic and metabolic) which are involved in the pathogenesis and therapy of diabetic nephropathy. The treatment must be based especially on strict control of glycaemia, decrease in arterial blood pressure, beneficial effect of low-protein diet, reduction of body weight and smoking prevention. The combination of the presented therapeutic procedures can slow down the progression of nephropathy and approximate it to the process of natural ageing. PMID- 11218951 TI - [Renal hypertension: pathogenesis and therapy]. AB - The kidney is both the source and target of high blood pressure. The pathogenesis of renal parenchymatous hypertension is significantly affected by sodium retention, inappropriate activity of vasopressoric systems and other factors. Drugs inhibiting the renin-angiotensin system are the treatment of choice in diabetic and non-diabetic nephropathies. The nephroprotective effect of long acting dihydropyridine calcium channel blockers as well as of other compounds is currently under investigation. PMID- 11218952 TI - [Diabetic nephropathy]. AB - Low-protein diet decreases hyperfiltration and albuminuria, and slows down the decrease in glomerular filtration in diabetic patients with incipient diabetic nephropathy (DN). The patients with incipient DN are recommended to intake 0.6 0.8 g of proteins per kg of body weight with a sufficient amount of essential amino acids. A high occurrence of urologic infections was found in risk groups of diabetic patients, namely in those with ketoacidosis, urinary bladder dysfunction in urogenital forms of autoimmune neuropathy, and in pregnant diabetic patients. Each symptomatic infection of renal parenchyma and urinary tract should be urgently treated. The cases with relapses of urinary tract infection should be subdued to a long-term prophylactic antimicrobial treatment. PMID- 11218953 TI - [Reconstruction of the gastrointestinal tract after esophagogastrectomy]. AB - The authors deal with the problems of reconstruction of gastrointestinal continuity after esophagectomy. They present the advantages of the stomach which is an especially good mediastinal as well as retrosternal substituent. One case of restoration of gastrointestinal continuity after both esophagectomy and gastrectomy by a jejunal loop with anastomosis on the neck is also presented. PMID- 11218954 TI - Health-status of the Slovak Republic population in comparison with countries of Central Europe and European Union. AB - The Central Europe (CE) countries are probably to become members of the European Union (EU) in a few years' time. This overview compares the health trends of Slovak Republic (SK) population in comparison with Central Europe countries (Czech Republic (CZ), Poland (PL) and Hungary (H)) and with the weighed mean of EU. The life expectancy of males and females at birth is significantly higher in EU, and this difference is not caused by substantially different infant mortality rate. Total premature mortality is significantly higher in CE and the differences in mortality due to cardiovascular diseases are the main cause of this gap. Cancer mortality in males, but not in females is the second most important difference. Breast cancer mortality rates in SK, CZ and PL are even lower than the EU average. Male mortality due to external causes is the third most important difference between EU and CE. The differences in mortality due to infectious diseases and due to diseases of respiratory system are not very great. After the political changes in 1989/90, the decline in cardiovascular mortality, mortality due to external causes and due to respiratory system diseases were observed in CE. Unfortunately, this is not true with cancer mortality. The rank of health status of four CE countries is as follows: the CZ is in the best situation, followed by SK and PL. There is an evident gap between these 3 countries and Hungary. The differences between EU and CE at the end of the 20th century are still relatively great, but in CZ, SK and PL there is the tendency to overcome this gap in the first 10-15 years of the next century. (Tab. 2, Fig. 6, Ref. 18.) PMID- 11218955 TI - The function of the cerebrospinal fluid space and its expansion. AB - In addition to its nutritive and protective effects, the basic function of the cerebrospinal fluid space resides in dynamic equilibration of pressure fluctuations caused by volume changes in three compartments contained within the rigid skull cavity: brain tissue, blood and cerebrospinal fluid. An increase in volume in one of them brings about a compliant withdrawal in volume in the other two. The degree of cerebrospinal fluid compliance can be expressed by means of the pressure/volume index which is directly proportional to this compliance. On the other hand an expansion of fluid space which forces the brain to withdraw its tissue, brings about the dilatation of brain ventricles. The degree of their dilatation depends on the effective pressure of cerebrospinal fluid which counteracts with the resistance of brain venous collectors. The blood in the venous network of the brain and cerebral extracellular fluid play a reversible role in cerebral mass restoration and reduction. These facts explain the reason why, from the physical point of view, the brain is considered to represent a viscous and elastic spongious matter. (Ref. 21.) PMID- 11218956 TI - ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive subscale)--validation of the Slovak version. AB - BACKGROUND: ADAS was designed to measure the severity of the most important symptoms of Alzheimer's disease (AD). Its subscale ADAS-cog is the most popular cognitive testing instrument used in clinical trials of nootropics. It consists of 11 tasks measuring the disturbances of memory, language, praxis, attention and other cognitive abilities which are often referred to as the core symptoms of AD. AIM: The aim of the study is to verify the Slovak adaptation of ADAS-cog and its ability to distinguish patients with AD from those with depressive disorders (DD). SUBJECTS AND METHODS: The study sample consists of 29 psychiatric inpatients divided into 2 groups: the AD group of 14 patients (4 males, 10 females, mean age 73.9 +/- 7.3 yrs) fulfilling NINCDS-ADRDA criteria of probable AD and the DD group of 15 subjects (6 males, 9 females, mean age 74.3 +/- 6.5 yrs) without any cognitive impairment. In all patients the ADAS-cog and SMMSE were administered. We compared the group in: total scores in both scales, task scores in the ADAS-cog and the scores of 3 ADAS-cog factors--memory, language and praxis. RESULTS: Both methods distinguished the patients with the AD from DD (p < 0.001 for both scales). Also other variables (task and factor scores of ADAS-cog) reflect the worse results of the AD group. The most evident differences between the diagnostic groups were found in the orientation and constructive praxis. The education level did not affect the scores of the ADAS-cog in the AD patients but it did in SMMSE scores in the DD group (p < 0.05). CONCLUSIONS: The Slovak version of ADAS-cog has distinguished the patients with the AD from those with DD. The most evident differences between the groups were found in orientation and visuo-constructive praxis. In DD patients, the risk of false positive findings in subjects with lower education is higher than in the AD patients. In comparison with the SMMSE, ADAS-cog seems to be more helpful in early diagnostics of AD. (Tab. 6, Fig. 3, Ref. 14.) PMID- 11218957 TI - [Influenza and influenza-like acute respiratory diseases in Slovakia in the 1999 2000 season]. AB - BACKGROUND: Acute respiratory infections (ARI) represent the most frequent cause of morbidity. Their epidemic outbreaks become a severe problem not only in healthcare, but also in economical and social spheres. OBJECTIVE: Presentation of epidemiological and virologic characteristics of the 1999-2000 influenza season in Slovakia; their comparison with the same Influenza season in other European countries, as well as with the situation during the preceding season in Slovakia. METHODS: The epidemiological analysis of Influenza and influenza-like diseases is based on the duty of attending physicians to report the number of new cases, complications, cases of working inability due to disease, and death cases. The reports are required on a compulsory weekly basis, and the reported cases are structured into 4 age groups. The laboratory diagnosis is based on virus isolation, rapid detection of antigen and serological tests. RESULTS: The outbreak of Influenza spread through Slovakia during the period between the 4th and 8th calendar weeks with its peak appearing during the 6th calendar week, when its incidence reached 2821 cases/100,000. The age group mostly afflicted by morbidity during the entire investigated season were children at the age of 0-5, while during the outbreak, the highest morbidity was reported among school children at the age of 6-14. The epidemic broke out on the entire territory of the Slovak Republic at the same time. 5 death cases were reported. Complicated cases were reported in 6.1% of the diseased. 34.1% of the group at the age from 15 to 59 were reported to be unable to work due to disease. 25 isolates of influenza virus were obtained from 505 nasopharyngeal swabs. 2 strains were found to be atigenetically similar to the vaccine strain A(H3N2)/Sydney 5/97 and A(H3N2)/Moscow 10/99. Regarding ARI aetiology, influenza viruses were serologically confirmed in 1356 samples; out of which type A(H3N2) was confirmed in 930 cases, A(H1N1) in 143 cases, type B in 283 cases; adenoviruses were detected in 467 samples; RS viruses in 779 samples; and Mycoplasma pneumoniae in 859 samples. Mixed infection caused by two viruses was diagnosed in 27 cases. DISCUSSION: The outbreak which hit Slovakia in the 1999/2000 season was a part of the European epidemic wave. As to its extent, it was a mild epidemic outbreak. It was significantly low as to its incidence among children. During autumn months, ARI aetiology was dominated by M. pneumoniae, viruses of type A(H3N2) prevailed. CONCLUSION: The identification of strains isolated during the investigated season confirmed that strains of influenza virus similar to strain A(H3N2)/Sydney 5/97 which is contained within the vaccine which has been assessed for this season, circulated in Slovakia during the past two subsequent seasons. Similar experience was reported from the majority of European countries involved in the international WHO programme of influenza Surveillance. These facts explain the mild extent of the investigated epidemic outbreak. (Tab. 5, Fig. 7, Ref. 8.) PMID- 11218959 TI - [Skin manifestations of Lyme borreliosis--occurrence, diagnosis, therapy]. AB - Eight genotypes of Borrelia burgdorferi are known currently. In Slovakia (Carpathian Euroregion) the most frequent genotypes are B. garini, B. afzelii, as well as B. valaisiana and B. lusitaniae. Infestation of the vector Ixodes ricinus is 3-30%. The most frequent early skin manifestation is erythema migrans (60 70%). Borrelia burgdorferi is suggested to be the causative agent in sclerodermia circumscripta, lichen sclerosus et atrophicus, maybe also in urticaria chronica, granuloma anulare, erythema anulare, erythema nodosum. It can be the causative agent also in neurological diagnoses as e.g. chronic oligosymptomatic encephalopathy, "sclerosis multiplex-like" syndrome and fatigue syndrome, arthralgia, myalgia, seronegative indifferentiated oligoarthritis and fibromyalgies. The serological diagnosis has to be coincide with clinical findings. Used serological examinations are ELISA, Immunoblot, indirect immunofluorescence examination. PCR is an important contribution in examination of synovial fluid (85% detection) and cerebrospinal liquor (24-100%). The importance of PCR is stressed in cases with mixed infections by several borrrelia genotypes. The first line treatment includes doxyciclin, amoxicilin, and erythromycin. The second line includes macrolides, cephalosporines. New perspectives are ascribed to active immunisation with recombined antigen OsA (LYMErix, ImuLyme). PMID- 11218958 TI - [Induction of autoimmune phenomena in lymphoproliferative diseases]. AB - The association of lymphoma with the positivity of antinuclear antibodies is unclear. The predisposition to neoplasma in the group of patients with systemic autoimmune diseases is known. Our case report contains steps of the differential diagnostic procedure leading from the diagnosis of systemic lupus erythematosus to the final assessment of non-Hodgkin lymphoma. (Ref. 11.) PMID- 11218960 TI - [Current views on seborrheic dermatitis]. AB - Seborrhoeic dermatitis is a common polyaethiological chronic disease affecting mainly the skin of face and scalp. The paper informs about aetiopathogenetic factors and clinical signs of SD. It review the contemporary methods of both external and internal treatments. Topical antimycotic treatment focused on Pityrosporum ovale, which could be the main causative agent, is considered to be the most important approach. PMID- 11218962 TI - [Cardiovascular diseases at the turn of the millenium]. AB - The coronary disease of the heart (CDH) will be the most frequent cause of mortality and inability to work in the 21st century not only in industrially advanced countries but also in the developing countries. This unfavourable, assumedly paradoxical tendency persevering despite the significant progress in diagnosis and therapy is caused by two circumstances: ageing of population (prolonged mean life expectancy) and the increase in the number of individuals afflicted with (CDH) and living up to high age. In result of this development, the rapid increase in the prevalence of heart failure, especially in the aged, becomes the main cause of mortality, morbidity and hospitalisation. PMID- 11218961 TI - [Clinical and pharmacologic aspects of mitochondrial nephropathy]. AB - Mitochondrial diseases, rated as rarities in paediatrics and neurology, become to be more and more frequently diagnosed in various body systems, including the kidneys. In nephrology, mitochondrial defects play an important role in the pathogenesis of tubular syndromes, interstitial nepohritis, focal and segmental glomerulosclerosis. PMID- 11218963 TI - [Diabetic neuropathy]. AB - Author in his article shortly describe pathogenetic mechanisms, clinical manifestations, diagnostic procedures and screening possibilities (which are very easy to perform), and also therapeutic methods of diabetic neuropathy. PMID- 11218964 TI - [Somatic and functional profiles of members of the Slovak karate team]. AB - The exercise load in karate is prevailingly of anaerobic character, the fact of which is evident by the increase in heart frequency and the levels of blood lactate. During competition, the heart frequency achieved the values of 180-199 beats per minute and the level of blood lactate following the competition was 4.5 6.5 mmol/l. The values of lactate were substantially higher during the training unit (at the time of chronometric measurement) when exercise was more intensive 5.8-12.5 mmo/l at the heart frequency of 180-200 or even more beats per minute, than during competition. The aim of this work was to find out the basic morphologic and functional profiles in the representatives of the National Karate Team on the basis of laboratory methods. PMID- 11218965 TI - [Association of type I diabetes mellitus with HLA alleles]. AB - Insulin-dependent diabetes mellitus is a chronic autoimmune disease characterised by a loss of tolerance towards own antigene structures beta-pancreatic cells. The destruction of cells subsequently leads to the loss of insulin production. There are more factors which trigger the autoimmune response in susceptible individuals, however, they are only partially known so far. One of the predisposing factors is the genotype, while the main role is ascribed to genes of the main histocompatible complex (HLA). Out of extensive genetic and epidemiological studies, the Caucasoid population is known to have a significant association of insulin-dependent diabetes mellitus with the increased frequencies of haplotypes HLA-DRB1*04-DQA1*0301-DQB1*0302 and DRB1*0301-DQA1*0501-DQB1*0201. PMID- 11218967 TI - [Telemedicine: something more than just "long-distance medicine"]]. PMID- 11218966 TI - Anatomy into the future. AB - The necessary increase in the clinical components of the medical curriculum has created pressure to reduce the amount of time spent on basic science, particularly the detailed learning of anatomy. Methods of learning must be re evaluated, but departments will be constrained by resources available. The clinical aspects of anatomy should form the principles of a core course, with a limit to the wider anatomical knowledge required. Feedback from the students is recommended as an initial form of monitoring the course. (Ref. 13.) PMID- 11218968 TI - [Adolescents and sources of sex information: preferences and perceived usefulness]. AB - OBJECTIVES: To find adolescents' assessment of the information received at their school on questions relating to sexuality. To discover their main sources of information on sexuality, the perceived utility of these and their preferences. DESIGN: Observational study. SETTING: Province of Cordoba. MEASUREMENTS AND MAIN RESULTS: 955 adolescents at secondary schools were chosen through multistage randomised sampling. Anonymous health questionnaire. Average age was 16.62% were girls. 545 valued as a lot or sufficient the AIDS information received (57%; 54.3 59.6), more than when asked about STD (29%; 25.4-31.9), contraceptives (33%; 29.7 35.2), sexual relations (22%; 19.5-24.1) or pregnancy (22%; 19.3-24.2). They were able to talk openly about sexuality, firstly with friends (90.8%) and girl/boy friend (80.5%), and least with teachers (18.7%), parents (17.4%) or priests (8.9%). Sexual information came basically from friends (26%) and magazines (24%), and least from doctors (7%) and parents (6%). The most useful source for adolescents was magazines (21%) and teachers (21%), with parents and cinema/T.V. in the last positions. When adolescents were asked from whom they would prefer to receive information, they chose firstly parents (34%) and doctors (33%). CONCLUSIONS: Adolescents perceived a centering of the information received at their school on AIDS. Their preferred sources of information did not coincide with what was most accessible. Despite considering doctors as a preferred source, they have received little information from us. The usefulness given to magazines is worthy of note. PMID- 11218969 TI - [Cost-effectiveness of atorvastatin against simvastatin as hypolipemic treatment in hypercholesterolemic patients in primary care]. AB - OBJECTIVE: To perform an economics evaluation of lipid-lowering therapy with atorvastatin and simvastatin in patients with hypercholesterolemia in primary care setting. DESIGN: Cost-effectiveness analysis (CEA) has been carried out by means of an open, random, prospective, "real world" study, with hypercholesterolemic patients (total cholesterol [TC] > 240 mg/dl and cLDL > 160 mg/dl). PATIENTS: A total of 92 patients were included (44.8% males), with a mean age of 64.9 +/- 9.4 years old (mean +/- standard deviation). 41.4% were diabetics, 62.1% hypertensives and 16.1% smokers. INTERVENTIONS: Patients were allocated to simvastatin 20 mg/day (44) and atorvastatin. 10 mg/day (48) for 6 months. ASSESSMENT AND MAIN RESULTS: Both therapies reduced significantly cLDL, TC and triglycerides at the end of the study. Atorvastatin reduced lipids faster than simvastatin at 3 months (p < 0.05), but significant differences could not be observed at 6 months. Atorvastatin reduced cLDL levels by 21.5 +/- 13.2% and 23.8 +/- 13.9% at 3 and 6 months, respectively, versus 16.4 +/- 14.2% and 22.8 +/- 10.8% with simvastatin. By these reductions, 54.2% of patients treated with atorvastatin and 50.0% of those allocated to simvastatin reached therapeutic goals of cLDL control. Atorvastatin 10 mg was more cost-effective than simvastatin 20 mg; 95,406 versus 101,335 pts per patient reaching therapeutic goals, respectively, which means that simvastatin need an extra cost of 24,833 pts per patient reaching therapeutic goals to be as efficient as atorvastatin. Sensitivity analysis to control for uncertainty confirmed the results of cost effectiveness analysis. CONCLUSIONS: Both statins were effective as lipid lowering agents. However, atorvastatin 10 mg was more efficient than simvastatin 20 mg due to a better cost-effectiveness ratio. PMID- 11218970 TI - [Motives for consultation and demographic characteristics of a community of "undocumented" immigrants in the district of Usera-Villaverde (Madrid)]. AB - OBJECTIVE: The objectives of the present study are to describe to the social particularizations, reasons for consultation and diagnoses conducted in the adult immigrants without regularizing that they went to this doctor's office in the district of Villaverde-Usera (Madrid), excluding the data from obstetrics gynecology and pediatric. DESIGN: One is a descriptive observational study, based on the registry of the daily activity of the consultation from 1996 to 1999. SETTING: Primary level of attention in the area of influence of the municipal districts of Villaverde-Usera. PARTICIPANTS: 1496 consultations to immigrants without regularizing adults, taken care of in our consultation are described in the mentioned period. MEASUREMENTS AND RESULTS: By means of the registry of daily activity social and demographic variables took shelter, of reason and type of consultation, as well as of the main diagnosis that brought to them to the consultation, en 1496 consultations of illegal immigrants (533 people). 31% of the consultations were new and a 14% of absences to the citation were registered. 67% of the consultations made women, the average age was of 34.9 years and in a 76% it referred like South America origin. The diseases that more consultations generated were acute respiratory infection 18%, depressives disorders 11% and the backache with also a 11%. The 48% the reasons for the consultation were acute and 60% took place to free demand. CONCLUSIONS: The group of consultations taken care of responds to the profile of a young South American woman, that fundamentally consults by acute respiratory infections, and very in proximity by depressive anxious upheavals and lumbar affections, problems very in relation to his situation of immigrant. The irregularity adds to a risk when making difficult the access, most of the consultations are precise, failing in elevated occasions to the programmed consultation. PMID- 11218971 TI - [Secondary prevention of ischemic heart disease in primary care (PRESENCIAP)]. PMID- 11218972 TI - [Women's attitudes to menopause and predictive variables]. AB - OBJECTIVE: To find what women's attitudes to the menopause are and how these attitudes relate to certain personal variables. DESIGN: Multi-centre, transversal study. SETTING: 5 clinics at three urban and teaching health centres in Granada. PARTICIPANTS: A systematic randomised sample of women = 18 who attended on demand in June 1998: alpha = 0.05, accuracy = 3 and standard deviation from the scale of attitudes (SA), found through prior sampling, was 15.4. N = 101 women. INTERVENTIONS: Questionnaire through interview after consultation. MEASUREMENTS AND MAIN RESULTS: Dependent variable: scale of attitudes to the menopause with 29 items. INDEPENDENT VARIABLES: age, marital status, educational qualifications, work situation, cultural group, religion, continuity with her doctor, utilisation, menopausal status, perception of autonomy, opinion of the menopause, feelings towards the menopause, perceived health. ANALYSIS: homogeneity and validity of SA. Descriptive, univariate analysis of SA with independent variables. Multiple linear regression: we found 7 factors that explained 66.5% of variance. Age 43.4 +/- 17.5. 50.5% had not reached the menopause; 10.9% were in the peri-menopause; and 37.6% in the menopause. 70.3% had feelings of relief or were neutral; 54.5% had a positive view; and 21.8% expressed no opinion. The variables explaining attitudes were feeling, continuity, opinion, utility, autonomy and perceived health. CONCLUSIONS: Women had positive or neutral feelings and opinions about the menopause. Their attitudes to it were related to these variables and not to other social or demographic variables or to their menopausal status. PMID- 11218973 TI - [Pharmacologic interactions in chronic treatments: corrective measures for its prevention in a basic area of rural health]. AB - OBJECTIVES: To identify the pharmacological interactions of clinical relevance (PICR) in the medication authorization cards (MAC) of the chronically ill and to establish strategies to minimise their appearance. DESIGN: Cross-sectional descriptive study. SETTING: Rural primary care centre. PATIENTS: Random sample of 626 MAC out of a total of 1306. MEASUREMENTS AND MAIN RESULTS: In December 1998, the following was gathered for every MAC with more than one drug treatment: age, sex, number of drugs, intrinsic value, drugs prescribed, daily dose and pharmacological interactions (PI), classified (using the scale of Hansten 1996) into light and clinically relevant. STATISTICAL ANALYSIS: Mantel-Haenszel (alpha = 0.05). Patients' mean age was 69.1 (95% CI, +/- 1.2). Mean number of drugs per MAC was 4 (95% CI, +/- 0.2). 341 PI affecting 197 patients (31.5%, 95% CI, +/- 3.6) were identified. 24.9% (95% CI, +/- 4.5) were PICR, detected in 11.7% (95% CI, +/- 2.5) of the MAC. The existence of PI was related to the number of drugs prescribed to each patient (p < 0.01). There were 26 PI with drugs of low intrinsic value (7.6%; 95% CI, +/- 2.8). 74.1% (95% CI, +/- 9.3) of the total PICR could be avoided by simple recommendations; and the remaining 25.9% (95% CI, +/- 9.3) by monitoring and follow-up of patients. CONCLUSIONS: It is important to identify the medications most commonly involved in the PICR so as to establish corrective measures to minimise the risks arising from multiple medication. Four educational messages advise on over 60% of the PICR detected. PMID- 11218974 TI - [Effectiveness of preventive activities at 8 years of their introduction in a general medicine practice in a health center]. AB - OBJECTIVES: Main: to assess the change in coronary risk (CR) in adults after 8 years of their involvement in the Programme of Preventive Activities and Health Promotion (PAPPS). Secondary: to determine the level of anti-tetanus vaccination reached and patients' compliance with activities. DESIGN: "Before and after" intervention study without random allocation. SETTING: A general medical clinic at a health centre. PATIENTS: 429 patients (204 men, 225 women) between 30 and 65 monitored for 8 years, recruited by active search for cases at daily consultations. INTERVENTIONS: Blood pressure, cholesterol, weight, tobacco habit, alcohol intake, anti-tetanus vaccination state, CR calculation at 10 years on the Framingham scale, and degree of compliance with activities were all determined at the start, at 4 years and at 8 years. Data was obtained from the clinical notes. RESULTS: Total population: a 0.8 drop in CR (CI difference: 0.4-1.2), equivalent to 8.5% of the initial figure. 64.4% increase in correct anti-tetanus vaccination (CI difference: 59.9-69). Compliance with activities at the start and after eight years: pressure 100%, 71%; tobacco consumption 99.5%, 71%; cholesterol determination 89%, 64%. Initially high CR sub-group: 6.7 drop of CR at 8 years (CI difference: 4.9-8.5), equivalent to 24.8% of the initial figure. CONCLUSIONS: In the total population, the CR drop found was not clinically significant, whereas in the initially high CR sub-group the drop was. There should probably be an active search made for patients with high CR and action taken on them. PMID- 11218975 TI - [Factors conditioning prescription in primary care]. PMID- 11218976 TI - [CUIDA'L: a clinical trial evaluating the effectiveness of an intervention in care givers]. PMID- 11218977 TI - [Applications of telemedicine in primary care]. PMID- 11218978 TI - [Family medicine and emergency medicine]. PMID- 11218979 TI - [Health economy and its application to evaluation]. PMID- 11218980 TI - [Users complaints]. PMID- 11218983 TI - [Feet on the ground and nothing grandiose]. PMID- 11218982 TI - [Care, professional career and teaching units]. PMID- 11218981 TI - [Treatment and control of arterial hypertension in the elderly]. PMID- 11218984 TI - [Traveling to the world of osteoporosis]. PMID- 11218985 TI - [Double-blind study on the efficacy of long-term intermittent nasal elcatonin in recent postmenopausal women]. AB - FUNDAMENTALS: Continuous treatment with calcitonin (CT) has caused an increase of bone mineral density for the first 18 months, followed by a partial decrease of it. In order to obtain a better result in a two year follow-up, it is proposed a schedule treatment during 50% to 66% of the time in recent postmenopausal women. METHODS: Pilot, double-blind, randomised, two years follow-up study. 60 women with osteopenia less than 5 years from menopause received 40 U of intranasal elcatonin (ELC) or placebo (PL) 2 months ON, one month OFF. Compliance, safety, pain and the degree of incapacity were evaluated at baseline and every 3 months. At the start and every six months lumbar and femoral BMD were assessed with DXA. RESULTS: 41 patients completed the study (21 ELC and 20 PL). There were no basal differences. The treatment was actually used during 59% of the follow-up time in the ELC group and during 58% of the time in the PL group. Basal T-scores were 2.29 SD in the PL group and -2.42 SD in the ELC group. Bone densitometry showed an increase of BMD in the group of patients treated with ELC up to 18 months (lumbar and femoral) but a loss in those patients that received PL. CONCLUSION: 40 U of nasal elcatonin for more than 50% of the observation time prevents in the long-term (2 years) the progressive loss of bone mineral density in recent postmenopausal women. PMID- 11218986 TI - [Fibronectin as a diagnostic marker in several determined neurological diseases]. AB - OBJECTIVE: To determinate if fibronectin in CSF can be a useful parameter in the diagnosis of some neurologic illnesses. MATERIAL AND METHODS: We have studied 30 patients, subdivided in four groups, depending on the type of neurologic illness. We have chosen as control a 10-patient group, which came to the Emergency Service and were diagnosed as a suspicious of neurologic illness, but after this it was discarded. In the whole group we practiced a lumbar puncture, with cytology, systematic, biochemistry, cultures, immunoglobulins determination and fibronectin quantification by ELISA. RESULTS: We want to emphasize the increase in fibronectin levels in CSF in both the patients with bacterial meningitis and the multiple sclerosis groups, when it's compared with the control group. CONCLUSION: For this, the determination of fibronectin levels in CSF might be a useful parameter in the diagnosis of some neurologic illnesses. PMID- 11218987 TI - [Evaluation of the functional component underlying the frequent attendance to a hospital emergency service and its economic consequences]. AB - OBJECTIVE: To analyse the psychosocial characteristics of frequent emergency department (ER) users with a relevant non-organic component and estimate the generated costs. METHODS: Retrospective-descriptive study (Jan 1996-Jun 1997) about overusers (OU) defined as > = 3 visits/6 months during at least two 6 months periods, coming to our hospital's emergency department. Reviewing their medical records and making a psychiatric interview we identified Non-organic OU (NOU). Subsequently we estimated the cost generated by discharge visits during the first six months of 1997. RESULTS: Sixty six out of 220 OU were identified as NOU. The mean consultation rate was 11.3 +/- 9.4. Clinician-psychiatrist agreement on non-organicity was 72.7%. The most frequent diagnoses were: personality disorders (37.5%) and depression-anxiety (35%). Psychiatric OU were significantly younger (51.7 vs 62.5 years) and attended more often (17.6 vs. 9.9 times). In six months only one of 240 ER consultation cause admission. The mean cost of each discharge episode was 8682.9 +/- 6633.8 pta (25.06% due to variable costs). The cost per minute of emergency room stay was 19.26 ptas. Overall NOU attention cost during the six month period studied was 1,903,775 ptas (0.36% of overall ER costs). CONCLUSIONS: Compared with the rest of users, NOU entail a higher burden for the ER. Mentally-ill patients are younger and consult more frequently than the rest of OU. Only 25% of the cost per consultation is due to treatments, tests or diets. PMID- 11218988 TI - [Echography evaluation of Morton's neuroma]. AB - OBJECTIVE: We have carried out a study to evaluate diagnostic usefulness of ultrasound in Morton's neuroma. METHODS: Twenty five patients with symptoms suggestive of Morton's neuroma underwent ultrasound examination of the forefoot. All patients subsequently had surgical treatment. RESULTS: Nineteen patients had sonographic evidence of neuroma which were confirmed surgically and later by histological exams. One patient had sonographic evidence of a neuroma that was not confirmed surgically. The remaining five patients did not have sonographic or surgical evidence of neuroma in spite of clinical signs and symptoms. No adjacent neuromas were appreciated. Ultrasound accurately predicted the location of the neuroma in 96.7%. Ultrasound demonstrated a sensitivity of 100% and a specificity of 83.3%. CONCLUSION: We conclude that ultrasound is a highly accurate technique in the diagnosis of the presence and location of Morton's neuromas. PMID- 11218989 TI - [Diagnosis of hemochromatosis with magnetic resonance]. AB - Hemochromatosis is a disorder of parenchymal iron overload. The diagnosis is based upon clinical manifestations, laboratory findings and iron concentration in liver. Magnetic resonance imaging (MRI) shows a decrease in liver signal intensity. Its role has not been already defined. Nonetheless, ratio of liver to muscle proton density (LMPD) shows a significant correlation with hepatic iron. One patient with a long-standing cirrhosis with data of hemochromatosis whose coagulation study did not allow to perform a liver biopsy was diagnosed with this method. Hepatic iron concentration was calculated based upon: microgram/g of hepatic iron = (-5.174* LMPD) + 9.932. MRI can be useful in the evaluation of hemochromatosis among patients who refuse or have contraindication to liver biopsy. PMID- 11218991 TI - [Meningeal carcinomatosis as first manifestation of carcinoma of the bladder: report of 2 cases]. AB - Meningeal carcinomatosis may occur in 0.8-8% of patients with solid tumors. The most common tumors associated with that condition are breast and small cell lung cancer. Meningeal carcinomatosis from urothelial cancer is rare, and it appears described in advanced stages of disease, generally, after chemotherapy. Two cases of meningeal carcinomatosis as the first manifestation of bladder cancer were reported. In the first case, a 46-year-old man presented signs and symptoms indicative of involvement of the spinal roots, subsequently neurologic dysfunction of the brain and cranial nerves appeared. In the second case, a 68 year-old man was admitted to our hospital with a history compatible with panhypopituitarism and pulmonary lymphangitic carcinomatosis from cancer of unknown primary site. Follow-up revealed a transitional cell carcinoma of the bladder and hydrocephalus due to cerebrospinal fluid outflow obstruction. We emphasize in the polymorphic presentation of meningeal carcinomatosis and the necessity to consider the bladder as primary tumor localization. PMID- 11218990 TI - [Nocardiosis in 2 immunocompetent patients]. AB - Two diagnosed clinical cases of nocardiosis in immunocompetent patients are presented, different in their clinical aspects, evolution and treatment. We report a 55 years-old man with disseminated nocardiosis and a 32 years-old man with splenectomy diagnosed of pulmonary nocardiosis. The medical literature is reviewed and emphasis is placed on the different illness and treatment of the nocardiosis. PMID- 11218992 TI - [Gastric anisakiasis diagnosed with endoscopy]. AB - Anisakiasis is a parasitic infestation, infrequent in Spain, due to ingestion of raw or underdone by Anisakis larvae. Also it can appear after consumption of smoked, salted or dried salt fish. The disease can show under different clinical forms, depending on the part of the gastrointestinal tract where the larva settles. We report two cases of anisakiasis diagnosed in Valladolid. Both patients were women that had eaten some days before anchovies marinated with vinegar. The diagnosis was made by endoscopic examination and the problem was solved by extraction of the parasite. It worthy to note that both cases appeared in a short time interval, showing perhaps some seasonal character. Finally some hygienic-dietetic measures are proposed for combating the disease. PMID- 11218993 TI - [Diffuse T-cell lymphoma of the cervix uteri: an unusual localization of an infrequent tumor]. AB - Non-Hodgkin lymphomas are frequent tumors. However, extraglandulary forms are very unusual, and the location in the uterine cervix is also extraordinary. A case of an elderly woman with symptoms not related with the tumor, in whom the diagnosis was made from the incidental finding of a distended obstructive bladder is presented. Pelvic mass is one of the forms of presentation of primary malignant lymphomas of the uterine cervix. Diagnosis was made in this case by transvaginal biopsy under general anesthesia. Biopsy showed a diffuse T-cell lymphoma, a very rare finding considering that most of published cases are B-cell type. The importance of distinguishing malignant lymphoma from undifferentiated carcinoma or sarcoma is emphasized since cervical malignant lymphoma can be successfully treated with irradiation. PMID- 11218994 TI - [Chemotherapy and palliation in patients with advanced cancer]. AB - Chemotherapy shows antitumoral activity in several advanced cancers. However, toxicity is frequent and may even overwhelm the clinical benefit of antineoplastic activity. To recommend such a treatment, we need to know the sensibility of cancer to therapy, its toxic effects and the clinical benefit we are looking for, expressed as: symptoms relief or delay in its presentation, improvement in quality of life, increase in overall survival and reduction in tumor volume. We need also to evaluate the performance status and functional status of each patient, its prognosis, the severity of symptoms and its interest to receive any antitumor treatment. According to these parameters we can individualize each therapy to select those patients whose expected benefit from this palliative chemotherapy is higher. PMID- 11218995 TI - [Acute pancreatitis complicated by a tubercular abscess]. PMID- 11218996 TI - [Hepatic epithelioid hemangioendothelioma: presentation of a case]. PMID- 11218997 TI - [Symptomatic hypocalcemia in an adenocarcinoma of the prostate with osteoblastic metastasis]. PMID- 11218998 TI - [Toxic epidermal necrolysis in relation with nevirapine]. PMID- 11218999 TI - [Massive rhabdomyolysis after an overdose of intravenous drugs complicated by acute acute renal failure and generalized compartment syndrome]. PMID- 11219000 TI - [Pellagra: manifestations of a disease. . . not forgotten?]. PMID- 11219002 TI - [Leishmaniasis in the cellular block of bone marrow aspirate]. PMID- 11219001 TI - [Acute adrenal insufficiency secondary to a bilateral adrenal hemorrhage]. PMID- 11219003 TI - [Pneumonitis in a 73-year-old woman]. PMID- 11219004 TI - [Xanthogranulomatous pyelonephritis with fistula in the gluteal region]. PMID- 11219005 TI - Peptide bond characteristics. PMID- 11219006 TI - Synthetic Cu(II) and Ni(II) peptidases. PMID- 11219007 TI - Palladium(II) and platinum(II) complexes as synthetic peptidases. PMID- 11219008 TI - Protease activity of 1,10-phenanthroline-copper systems. PMID- 11219009 TI - Specific protein degradation by copper(II) ions. PMID- 11219010 TI - Artificial iron-dependent proteases. PMID- 11219011 TI - Lanthanide ion-mediated peptide hydrolysis. PMID- 11219012 TI - Hydroxyl radical footprinting of proteins using metal ion complexes. PMID- 11219013 TI - Nickel- and cobalt-dependent oxidation and crosslinking of proteins. PMID- 11219014 TI - Effects of metal ions on the oxidation and nitrosation of cysteine residues in proteins and enzymes. PMID- 11219015 TI - Protein cross-linking mediated by metal ion complexes. PMID- 11219016 TI - Ferrocenoyl amino acids and peptides: probing peptide structure. AB - Recent studies clearly show the utility of the carbodiimide protocol to attach the redox-active Fc moiety to the N-terminal side of amino acids and peptides under mild conditions, resulting in stable and often crystalline products that afford themselves to structural analysis by X-ray crystallography. Electrochemical studies of Fc-peptides show that there is a significant influence of the redox potential depending on the amino acid sequence. The Fc moiety is sensitive to structural changes that occur in the peptide to which it is attached. For helical Fc-oligoprolines, the redox potential of the Fc group makes it easier to oxidize as the oligoproline chain increases in length. Nonhelical peptides, having a similar primary but different secondary structure, give rise to very different redox potentials. The ramifications of these findings to biological systems are significant in that they provide further evidence that the redox properties of a metal center are influenced by factors that go beyond the primary ligand sphere and thus for the involvement of long-range interactions. The Fc group is clearly sensitive to the shape of the peptide. These effects are currently under more detailed investigation [45] in order to gain further insight into the electronic structure of these ferrocenoyl peptides. Although we are not yet in a position to distinguish between "sensing" coordination or "sensing" conformation changes, this effect is of interest because it may allow the development of peptidic sensors. PMID- 11219018 TI - Co(III)-promoted hydrolysis of amides and small peptides. PMID- 11219017 TI - Synthetic analogs of zinc enzymes. PMID- 11219019 TI - Mimicking biological electron transfer and oxygen activation involving iron and copper proteins: a bio(in)organic supramolecular approach. PMID- 11219020 TI - Soft papules on the forearm. Lesions that can be compressed are often benign and do not require surgery. PMID- 11219022 TI - How to predict your patient's future. PMID- 11219021 TI - Hypertension. Update on use of angiotensin II receptor blockers. AB - Hypertension is the most common of the cardiovascular risk factors. Although its risks have been known for decades, hypertension remains inadequately diagnosed and undertreated. Better understanding of the pathophysiology of hypertension, including the role of the renin-angiotensin system, has led to the development of new approaches for patient management. Compared with traditional antihypertension treatments, angiotensin II receptor antagonists may offer more effective treatment and an improved side effect profile. These agents also may have an important treatment role in other cardiovascular conditions for which ACE inhibitors are commonly prescribed. As clinical trial data are showing, the full potential of these drugs has yet to be determined. PMID- 11219023 TI - Prescribing. Keys to maximizing benefit while avoiding adverse drug effects. AB - When prescribing for older patients, some physicians are overly cautious, and this strategy can result in a less than optimal treatment outcome. The reluctance to treat aggressively is understandable because the geriatric population is susceptible to adverse drug reactions. The key to maximizing therapy lies in individualizing it as much as possible. There are a number of steps physicians can take to ensure that their patients are not being undertreated. These steps include regular reevaluations of dosages and plasma drug concentrations, recognition and understanding of drug side effects, and avoidance of certain agents. Close monitoring allows physicians to minimize risks, maximize benefits, and get the most out of what modern medications can do to help older patients. PMID- 11219024 TI - Prostate cancer Tx. Therapeutic options based on tumor grade, life expectancy, and patient preferences. AB - Cancer of the prostate is the most common malignancy in American men. Its incidence is associated with age, race, family history, and life style factors, such as high-fat diets. Some men develop prostate cancer before age 55, but 80% of tumors occur in men older than age 65. For organ-confined prostate cancers, treatment options include observation, radical prostatectomy, external beam or interstitial radiation, and cryoablation. The appropriate therapeutic decision is based on analysis of multiple factors by the physician and the individual patient. Advanced prostate cancer remains incurable, but hormonal manipulation and newer chemotherapeutic regimens offer palliation in later stages of the disease. PMID- 11219025 TI - Treatment of impulsivity and aggression in a patient with vascular dementia. AB - This case illustrates how treatment with divalproex sodium, an agent approved for use as an anticonvulsant and mood stabilizer, led to a reduction in overt aggression, diminished impulsivity, and improved functional status in a patient with vascular dementia. Improved receptivity to care and reduced hostility also led to an increased quality of life for the family caregivers. The daughter also benefited greatly from participation in a family support group. PMID- 11219026 TI - Iasis plans IPO. Hospital company hopes to woo investors with new management team. PMID- 11219027 TI - The watchdogs are biting. State attorneys general asserting authority over not for-profit hospitals. PMID- 11219028 TI - Hardly a sense of closure. N.Y. ambulatory center closes, blames move on hospital's tactics. PMID- 11219029 TI - New kids on the block. Here comes the next generation of workers: they have Gen Xers' energy and skills, with a new attitude. PMID- 11219030 TI - Casting a net via the Net. More healthcare organizations turn to online recruiting; results mixed. PMID- 11219031 TI - Web survey. December survey results: a look at 2001. PMID- 11219032 TI - Behind in the count. Purchase of money-losing hospital puts Ty Cobb health system in a slump. PMID- 11219033 TI - The PPO accreditation contest. Competition among the big guns may hamper universal standards. PMID- 11219034 TI - What would make your day perfect? PMID- 11219035 TI - Treating the underserved: you call this an incentive? PMID- 11219036 TI - Compliance plans: how optional, really? PMID- 11219037 TI - Prompt-pay laws are finally getting teeth. PMID- 11219038 TI - Moving on, moving up. Your career guide. Stuck midstream? Change horses. PMID- 11219039 TI - Making good use of a sabbatical. PMID- 11219040 TI - Back to college, at 49. PMID- 11219041 TI - Moving on, moving up. Your career guide. Some are meant to lead. Maybe you. PMID- 11219042 TI - "Perfect is the enemy of good". PMID- 11219043 TI - The ion chromatographic separation of high valence metal cations using a neutral polystyrene resin dynamically modified with dipicolinic acid. AB - A neutral polystyrene resin column, dynamically loaded with dipicolinic acid at a concentration of 0.1 mM in 1 M potassium nitrate eluent, was investigated for the separation characteristics of a number of high valence metal cations over the pH range 0-3. The metal species studied were Th(IV), U(VI), Zr(IV), Hf(IV), Ti(IV), Sn(IV), V(IV) and V(V), Fe(III) and Bi(III), of which Ti(IV), Sn(IV), V(IV) and Fe(III) did not show any retention. For the remaining metal ions, significant retention was obtained with good peak shapes, except for Th(IV), which moved only slightly from the solvent front with some tailing. The retention order at pH 0.3 was Th(IV) < V(V) < Bi(III) < U(VI) < Hf(IV) < Zr(IV). A notable feature of this separation system was the high selectivity shown for uranium, zirconium and hafnium, the last two being nearly resolved in 15 min on the relatively short 10 cm column. PMID- 11219044 TI - Ion chromatographic analysis of hydronium ion using ODS modified with dodecylsulfate as the stationary phase. AB - The hydronium ion (H3O+), the most essential species to every field of chemistry, was successfully separated from other cations. This major goal was achieved by a HPLC approach in which a reversed-phase ODS which had been initially modified with dodecylsulfate was used as the stationary phase and an aqueous KNO3 solution was used as the mobile phase. Of all tested monovalent cations (analyte ions), the hydronium ion (H3O+) showed the highest affinity towards the stationary phase, followed by NH4+, Na+, and then Li+. The hydronium ion, after the separation, was directly detected using conductivity and the detection signal (conductivity) was in linear proportion (linear range 7.8 x 10(-4)-0.45 M; injection volume, 100 microL) to the concentration of the acid species of the tested sample. This proposed HPLC method was applicable to separate/detect H3O+ from both strong and weak acidic samples. PMID- 11219045 TI - Alloy electrodes with high hydrogen overvoltage for analytical use in voltammetry. Some preliminary results. AB - Liquid mercury and liquid diluted mercury amalgams have been the major electrode systems employed in voltammetry and related methods. This is mainly due to their high overvoltage to hydrogen, which enables the determination of heavy metals (zinc, nickel, cobalt, etc.) and other species with high negative half-wave potentials; the toxicity of mercury and liquid diluted mercury leads to ever increasing restrictions in their use. The use of such systems may even be forbidden in the future, at least in online systems for work in the field. Recent work, carried out in our laboratory, has demonstrated that a non-toxic solid dental amalgam may be used as the electrode material, conveniently replacing mercury. An extension of this work has shown that electrode materials comprising a metal or a compound with low hydrogen overvoltage change their hydrogen overvoltage properties substantially when contaminated with even small amounts of metals or compounds which show high hydrogen overvoltage. This extends greatly the range of potentially available electrode systems and thereby analytical possibilities of voltammetry. This new discovery also makes it possible to produce solid electrodes that have high overvoltage to hydrogen without any use of mercury. PMID- 11219046 TI - Assessment of growth of Fusarium solani by cyclic voltammetry and possible bioanalytical applications. AB - Fusarium solani, the fungus isolated from polyurethane waste scraps, was studied for its voltammetric response. The peak current values were obtained for different days and were plotted against time. This electrochemical method based on the voltammetric response showed all the four phases of the growth of the fungus. The growth curve obtained matched well with the conventional methodology, which is obtained by assessing the increase of dry weight of the organisms against time. The electrochemical method is more advantageous than the conventional method because the conventional method is very time consuming and difficult to work with. Further, the electrochemical method clearly shows the decline phase, which is generally not very well defined in the conventional method of assessment of the growth curve. It was confirmed by further experiments that the metabolites were responsible for the anodic peak and not the fungal biomass. Identification of the metabolites that are responsible for the anodic peak is presently being studied. PMID- 11219047 TI - A dual electrochemical sensor for nitrite and nitric oxide. AB - Nafion/lead-ruthenate pyrochlore chemically modified electrode (NPyCME) showed a remarkable dual sensing activity toward NO2- oxidation and NO reduction as demonstrated by cyclic voltammetry (CV), ac-impedance spectroscopy and flow injection analysis (FIA). The mechanistic parameters of current function, charge transfer resistance and exchange current for the NPyCME, GCE and Nafion-coated GCE were evaluated and compared. The disproportionation reaction of NIIIO2- into NIVO3- + NIIO in acidic solution was used as a model system for testing the dual sensing ability of the NPyCME. The obtained crossover peak response for NO2- oxidation and NO reduction in pH 1.65 buffer solution gave the direct proof for the applicability of the NPyCME in the dual electrocatalytic action. By flow injection analysis, under optimized conditions, the calibration curve was linear in the range of 100 nM-100 microM and 800 nM-63.3 microM and the detection limit (S/N = 3) was 4.8 nM and 15.6 nM for NO2- and NO, respectively. PMID- 11219048 TI - Refractometric discrimination of void-space filling and swelling during vapour sorption in polymer films. AB - Thin polymeric films have been deposited as upper cladding layers on a new integrated optical interferometer fabricated from layers of silicon oxynitride on a silicon wafer. The evanescent field of the probing waveguide mode transduces refractive index changes in the polymer layer into the measured phase changes in the device. Real-time measurement of index change and its sign is obtained. Upon exposure to humid air, we record water sorption by films of poly(vinyl pyrrolidone) by a rapid positive index change for void-space filling followed by a slow negative index change for swelling. Sorption of water vapor into a thin film of the viscous liquid polymer polyethylenimine shows only swelling mode behaviour and a simple constitutive model can be applied to give the fractional water occupied volume. PMID- 11219049 TI - mRNA isolation in a microfluidic device for eventual integration of cDNA library construction. AB - mRNA isolation for the purpose of cDNA library construction was performed in a microfluidic chip device using paramagnetic oligo-dT beads. The simple Y intersection flow design mixes beads and sample on-chip, and uses magnetic trapping to capture, then release the beads. The capillary gel electrophoresis (CGE) detection of the total unamplified mRNA isolated on-chip, and of a reverse transcription-polymerase chain reaction (RT-PCR) amplified rare gene indicated that mRNA could be captured by oligo-dT beads on-chip, had very good integrity and was suitable for constructing a cDNA library. The limit of detection for the rare bicoid gene of Drosophila Melanogaster corresponded to the capture of approximately 2.8 ng of total mRNA from 0.85 microgram of total RNA (TRNA) within the microchip. As much as 34 ng of total mRNA was estimated to be captured from 10 micrograms of TRNA. PMID- 11219050 TI - Chromatographic methods for the determination of the logL16 solute descriptor. AB - A squalane packed column and two open-tubular columns coated with an immobilized stationary phase film of poly(dimethylsiloxane) or poly(methyloctylsiloxane) are evaluated as surrogate chromatographic systems for the determination of the logL16 solute descriptor by gas chromatography. Retention on the squalane column is dominated by gas-liquid partitioning with a significant temperature-dependent contribution from interfacial adsorption at the liquid-solid interface. Using the gas-liquid partition coefficient as the dependent model variable allows logL16 to be estimated to +/- 0.026 log units over the temperature range 60-120 degrees C. Without correction for interfacial adsorption a single column estimation of logL16 with phase loadings of 8 to 20% (m/m) over the temperature range 80-120 degrees C is possible for compounds with moderate hydrogen-bond basicity. The poly(dimethylsiloxane) stationary phase is both dipolar and hydrogen-bond basic and less suitable than the poly(methyloctylsiloxane) stationary phase, which is less cohesive and has similar dipolarity but no hydrogen-bond basicity. The determination of logL16 on the poly(methyloctylsiloxane) column requires prior knowledge of the solute dipolarity/polarizability descriptor to avoid significant errors in the measurement of logL16 for polar compounds. In such circumstances a single column estimation of logL16 over the temperature range 60-140 degrees C with an error of +/- 0.05-0.09 log units is possible. PMID- 11219051 TI - High accuracy isotope dilution analysis for the determination of ethanol using gas chromatography-combustion-isotope ratio mass spectrometry. AB - A procedure was established for the determination of ethanol in water samples by isotope dilution analysis. After spiking the sample with labelled [13C2]ethanol, it was analysed by gas chromatography-combustion-isotope ratio mass spectrometry. Results are reported for two certified reference materials and also ethanol solutions prepared for a CITAC (Co-operation on International Traceability in Analytical Chemistry) interlaboratory comparison. The certified reference materials were certified using the dichromate titration method at nominal levels of 80 and 200 mg per 100 mL. The CITAC solutions were prepared gravimetrically at nominal levels of 50, 80 and 200 mg per 100 mL. The results of the analysis agree well to within 0.5% of the gravimetric values of the different samples. The relative expanded standard uncertainties (with a coverage factor equal to 2) associated with the results varied between 0.18 and 0.37%, a range that encompassed the gravimetric values for the different samples. A complete uncertainty budget was also drawn up so that the different contributions could be identified and quantified. The main contributions were due to variations in the measured isotope amount ratios and a 'between' blend component introduced to quantify the contribution of factors such as the degree of matching of the isotope amount ratios between standards and samples used in the isotope dilution analysis. PMID- 11219052 TI - A rapid method for the determination of lasalocid in animal tissues and eggs by high performance liquid chromatography with fluorescence detection and confirmation by LC-MS-MS. AB - A simple and rapid method has been developed for the extraction of lasalocid from chicken muscle, eggs and liver and kidney from chicken, pig, sheep and calf. This method allows the screening of a large number of samples, i.e. 30-40 within a working day, and has an overall analysis time of 90 min. Lasalocid standard solution can be detected at 1 ng ml-1 by both HPLC-fluorescence (HPLC-F) and LC MS-MS; the limit of quantification in fortified samples by the described method is 1 ng g-1. Results show good repeatability and mean 'spiked' recoveries by HPLC F in the range of 10 to 200 ng g-1 (ppb) of 103, 87, 107, 97, 97, 103, 93, 109 and 100% in chicken muscle, chicken liver, egg, pig liver, pig kidney, sheep liver, sheep kidney, calf liver and calf kidney, respectively. For concentrations between 1 and 6 ng g-1 of spiked lasalocid in eggs and chicken liver by LC-MS-MS, the average recoveries were 76 and 59%, respectively. PMID- 11219054 TI - Cross-referenced combinatorial libraries for the discovery of metal-complexing ligands: library deconvolution by LC-MS. AB - N-Acylthioureas are excellent ligands for a variety of heavy metals, but their metal selectivity is highly dependent on the precise nature of the substituents present. In this paper we show how combinatorial chemistry techniques can be used to establish relative affinities for copper within a mixture of 100 such thioureas. Following a straightforward synthesis, and copper extraction using standard liquid-liquid extraction techniques, LC-MS was used to identify the ligands which bind most strongly to the copper ions. Among the 100 ligands XC(O)N(Z)C(S)NHY, the most important substituent is the Y group bound to the NH: only aromatic Y substituents give strong binding to copper. The acyl X substituents are invariably aromatic, and an electron-rich X group is best; the affinity for copper seems to be less dependent on the Z substituent, although a large group such as benzyl disfavours copper binding. The five ligands from the library which bind copper most strongly have been clearly identified by a series of experiments: they all have aromatic groups in the Y position, but the X and Z substituents can be more varied. This is a very convincing demonstration of the power of combinatorial methods: to have found the same information by conventional methods would have required a lengthy and repetitive series of syntheses and investigations. In addition, our results give some preliminary evidence for synergistic binding of two different ligands, but this requires further investigation. PMID- 11219053 TI - Simultaneous quantitative determination of norgestrel and progesterone in human serum by high-performance liquid chromatography-tandem mass spectrometry with atmospheric pressure chemical ionization. AB - A selective, reliable and rapid method for the simultaneous determination of progesterone and norgestrel concentrations in human serum after taking oral contraceptive tablet has been developed using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MS) with atmospheric pressure chemical ionization (APCI) interface. The norethisterone was used as the internal standard. Selected transitions of m/z 313/245 for norgestrel, m/z 315/97 for progesterone and m/z 299/109 for norethisterone were monitored using multiple reaction monitoring (MRM) mode for quantitation. The assay was linear over the concentration range of 0.2-50 ng mL-1 for norgestrel and progesterone. The lower level of quantitation in human serum was obtained at 0.2 ng mL-1 for both norgestrel and progesterone using optimum tuning parameters. The intra-assay precision and inter-assay precision do not exceed 10 and 9%, respectively. The method has been applied to the determination of norgestrel and progesterone in serum of female volunteers. PMID- 11219055 TI - Automated in-tube solid phase microextraction coupled with HPLC-ES-MS for the determination of catechins and caffeine in tea. AB - A polypyrrole (PPY) coated capillary and several commercially available capillaries (capillary GC columns) were used to evaluate their extraction efficiencies for catechins and caffeine. Compared with commercial capillaries that were currently used for in-tube solid phase microextraction (SPME), the PPY coated capillary showed better extraction efficiency for all of the compounds studied. Electrospray mass spectrometric (ES-MS) detection conditions were also investigated. After optimization of the extraction and detection conditions, a method for the sensitive and selective determination of catechins and caffeine was developed by coupling the PPY coated capillary in-tube SPME with HPLC-ES-MS. Catechins could be determined in both positive and negative ion detection modes. The detection limit (S/N = 3) for each of the studied catechins was < 0.5 ng mL 1. Caffeine could only be determined under positive ES-MS detection conditions and its detection limit was 0.01 ng mL-1. Caffeine and the five catechins in several tea samples were determined using the developed method. Small amounts of catechins were also detected in grape juice and wine samples. PMID- 11219056 TI - Metal distribution patterns in the mussel Mytilus edulis cytosols using size exclusion chromatography and double focusing ICP-MS detection. AB - In order to estimate metal distribution patterns in biomolecules of different sizes and their possible relationship with environmental heavy metal contamination, multi-elemental distributions in different fractions of the cytosols of mussels were studied. To do so, samples were collected from natural populations of two coastal regions in Spain: a wild (uncontaminated) coast and an industrialised (contaminated) area in Asturias. Moreover, some commercial mussels from the Galicia coast were also investigated for comparison. Aliquots of the mussel cytosol extracts from each sample were applied to a calibrated Sephadex G 75 column (100 x 1 cm) and forty 3 ml fractions were obtained. After suitable dilution, 18 trace metals were determined by double focusing inductively coupled plasma mass spectrometry (DF-ICP-MS). The use of DF-ICP-MS detection allowed the resolution of several spectral interferences that cannot be resolved by quadrupole ICP-MS. Accurate results for ultratrace elements at basal levels are possible even after sample dilution to prevent matrix effects. After biomolecule metal association pattern has been established, quantitative analysis of mussel cytosols from the three coastal areas was carried out, using external aqueous calibration plus standard additions to correct for possible matrix effects. Results showed that total metal contents increased following the expected order: wild coast < Galicia coast < industrial area coast. Speciation of Cu, Zn, Ca, U, Ni, Mo, Mn, Cr, V, Cd, Al and Sb showed a similar distribution pattern among cytosolic ligands for all the studied samples. Conversely, Fe, Pb, Sn, Co, Hg and Ag were found to exhibit different speciation patterns when samples from industrialised (contaminated) and non-industrialised areas were compared. PMID- 11219057 TI - Determination of three anabolic compounds in calf urine by liquid chromatography with photodiode-array detection. AB - A method for the determination of three anabolic hormones (diethylstilbestrol, dienestrol and trenbolone) in calf urine is described. After enzymatic hydrolysis, the samples were cleaned up by C18 solid-phase extraction. Drugs were extracted with hexane and analyzed by isocratic elution on a Discovery RP-Amide C16 5 microns column with photodiode-array detection at 240 and 347 nm. Both retention time and UV spectra were used for identification. Detection limits for the HPLC system were calculated to be 0.3 ng injected for all analytes in the standard mixture. However, for urine samples these limits increased because of the presence of unidentified matrix components. After extraction from urine, the limits of detection for the whole analytical procedure were 5 and 10 ng injected for trenbolone and stilbenes, respectively. The average recoveries of the hormones from spiked samples were in the range 53.1-56.7% with RSD between 11.3 and 14.5% for the whole procedure in the concentration range 25-2.5 ng ml-1. PMID- 11219058 TI - Comparative study of capillary zone electrophoresis and micellar electrokinetic capillary chromatography for the separation of naphthalenedisulfonate isomers. AB - We investigated the separation of a test mixture of nine substituted and unsubstituted naphthalenedisulfonate isomers by capillary electrophoresis with a UV diode array detector. In particular, we focused on how the composition of the running buffer affected the separation selectivity. When capillary zone electrophoresis was carried out, the best results were obtained when organic solvents such as ethanol or propan-2-ol were added. Eight peaks were baseline separated but in no case were all the unsubstituted isomers separated. Therefore, capillary electrophoretic separation of the compounds was examined in the presence of micellar agents, such as sodium dodecyl sulfate, polyethylene glycol dodecyl ether (Brij 35) and cetyltrimethylammonium bromide. All the substituted isomers and two of the unsubstituted isomers were well resolved within 20 min by micellar electrokinetic capillary chromatography when Brij 35 was used as micellar agent. Separations were reproducible, in terms of peak area and migration time, under these conditions. PMID- 11219059 TI - Rejection of capillary wall background light in an on-column confocal fluorescence detector. AB - Minimization of the background arising from the capillary wall is of extreme importance in laser induced fluorescence on-column detection for capillary electrophoresis. A sensitive confocal fluorescence detection scheme is described. The intense capillary wall background light was effectively rejected by an adjustable precision slit in a confocal configuration. Rhodamine 640 was used as a standard fluorophore. Detection linearity was demonstrated over four orders of magnitude of concentration and the concentration detection limit was 3.38 x 10( 11) M. PMID- 11219060 TI - An electrospray ionization ion trap mass spectrometric (ESI-MS-MSn) study of dehydroascorbic acid hydrolysis at neutral pH. AB - The hydrolysis of dehydroascorbic acid (DAAH) at neutral pH and 27 degrees C was investigated by direct infusion electrospray ionisation ion trap mass spectrometry (ESI-MS). This approach permitted derivatisation and elution procedures to be avoided, reducing to the minimum extent sample manipulation and allowing a rapid and direct observation of the species involved in the reaction. Six main peaks, related to hydrated dehydroascorbate (HyDAA-) and diketogulonate (HyDKG-) anions, were observed in the mass spectra of DAAH solutions at different times of incubation and were characterised by MSn experiments. The relevant signal intensities changed with time and a model, based on the irreversible pseudo-first order HyDAA(-)-->HyDKG- conversion, fitted successfully the data obtained for dehydroascorbate. The kinetic constant of the process was (3.2 +/- 0.5) x 10(-2) min-1. The influence of metal ion traces on the hydrolysis rate was also checked, performing experiments in the presence of EDTA, and was found to be negligible. PMID- 11219061 TI - Enantioselective uptake of amino acid with overoxidized polypyrrole colloid templated with L-lactate. AB - An overoxidized polypyrrole colloid, which can recognise enantiomers of amino acids has been prepared by a newly developed molecular imprinting technique. A polypyrrole colloid, which had been polymerised from a mixture of pyrrole (monomer), polyvinylpyrrolidone (steric stabiliser), peroxodisulfate (oxidant) and L-lactate (dopant), was overoxidized to create a dopant-complementary cavity. The enantioselectivity of the overoxidized colloid was evaluated by comparing the uptake of L-alanine and L-cysteine with that of the respective D-enantiomers. The L/D uptake ratios for these amino acids were about 2, while phenylalanine showed suppressed uptake for both the enantiomers. The absence of phenylalanine uptake can be explained in terms of the molecular size, which is too large to be accommodated by the cavity created by L-lactate. In contrast, a colloid templated with L-phenyllactate took up L-phenylalanine with a higher enantioselectivity of about 7. A colloid templated with L-lactate was applied to surface chirality analysis through enantioselective adsorption on cysteine-modified gold surfaces. Quartz microbalance experiments and scanning electron microscope observation of the gold surface revealed that the colloidal particle has higher affinity to a surface modified with L-cysteine than to one modified with D-cysteine. PMID- 11219062 TI - Enzymatic hydrolysis of conjugated steroid metabolites: search for optimum conditions using response surface methodology. AB - The optimum conditions for hydrolysing conjugated metabolites of steroid hormones in bovine urine were performed with Helix pomatia juice, beta-glucuronidase from bovine liver and preparations of limpets and abalone entrails using response surface methodology. The experimental design and empirical modelling used allowed us to assess the main effects of factors (time, temperature, pH and enzyme quantity) and to predict the optimum conditions for each enzyme preparation. Confirmatory experiments were applied to check the predicted values and to validate the model. The comparison of the enzyme preparation efficiency for various conjugate steroids and the study of possible by-product synthesis led us to select abalone entrails to hydrolyse natural dehydroepiandrosterone, etiocholanolone, epitestosterone; 17 alpha-estradiol and estrone in bovine urine. The optimum conditions were found to be 20 h at 42 degrees C with the pH adjusted to 5.2 and using 12,000 units of enzyme preparation. PMID- 11219063 TI - A novel mimetic enzymatic fluorescence immunoassay for hepatitis B surface antigen by using a thermal phase separating polymer. AB - Iron tetrasulfonatophthalocyanine (FeTSPc), a peroxidase mimic, was used as a labeling reagent and poly(N-isopropylacrylamide) (PNIP) as the separation support of the immune complex for the mimetic-enzymatic immunoassay of hepatitis B surface antigen (HBsAg). PNIP was precipitated from aqueous solution when the ambient temperature was higher than its lower critical solution temperature of 31 degrees C. In a sandwich immunoassay, the antigen (HBsAg) first reacted with mouse anti-human HBsAg antibody immobilized on PNIP (PNIP-antibody) and then further reacted with FeTSPc-labeled mouse anti-HBsAg antibody (antibody-FeTSPc) at room temperature in a homogeneous format. After changing the temperature to separate the PNIP-antibody-HBsAg-antibody-FeTSPc conjugate moiety, it was re dissolved and determined by coupling with the fluorogenic reaction of hydrogen peroxide and p-hydroxyphenylpropionic acid. The sensitivity of this method (3 ng mL-1) was close to that of the traditional ELISA using the same reactants. However, the assay was much faster (the assay time decreased from 100-120 to 45 min). This method was applied to determine HBsAg in human serum with satisfactory results. PMID- 11219064 TI - Point-of-need diagnosis of cystic fibrosis using a potentiometric ion-selective electrode array. AB - The novel approach of using a micro-sensor array of miniaturised solid-state ion selective electrodes to analyse sweat samples for sodium, potassium and chloride simultaneously is described. The array, incorporated into a miniature flow cell which is linked to a portable PC for data acquisition, constitutes a small, portable, and simple to use analytical instrument. Samples are passed through the flow cell and over the array and an immediate potentiometric response is obtained, which can be equated to the concentrations of sodium, chloride, potassium and other parameters in the sweat sample. Used here in conjunction with a Wescor Macroduct sweat sampling unit, it promises a much simplified, much less expensive procedure for sweat analysis than the procedures currently in common use. PMID- 11219065 TI - Disposable, low cost, silver-coated, piezoelectric quartz crystal biosensor and electrode protection. AB - The use of a commercial, silver-coated, piezoelectric quartz crystal as a disposable, low cost and reliable immunosensor is presented. The protection of the silver electrode from undesirable oxidation was achieved by polystyrene or carboxy-poly(vinyl chloride) (PVC-COOH) modification. In addition to serving as protection for the electrode, polymer films provided a substrate for antibody immobilization by either physical adsorption or covalent linkage. Polystyrene modification showed an additional advantage of improvement of surface smoothness. The atomic force microscope (AFM) and scanning electron microscope (SEM) were used to evaluate the morphologies of polymer films obtained by dip or drop coating techniques. It was found that drop coating provided more significant improvement in surface smoothness than dip coating, and the resulting sensor surfaces were more suitable for in situ liquid phase assay. Although PVC-COOH modified sensors were not suitable for liquid phase assay because of the high surface roughness, the covalent linkages (amide bonds) between antibodies and COOH groups in the polymer film offered better sensor performance in ex situ assay in terms of a higher antibody binding capacity and better antigen detection sensitivity. PMID- 11219066 TI - Disposable potentiometric enzyme sensor for direct determination of organophosphorus insecticides. AB - A potentiometric disposable enzyme sensor for the direct and fast determination of organophosphorus (OP) insecticides was developed by using an organophosphorus hydrolase (OPH) immobilized on an ion-selective electrode. The disposable screen printed transducer was based on double matrix membrane technology which allows easy mass production. The potentiometric device consisted of a H(+)-sensitive electrode with integrated Ag/AgCl reference electrode. The electrodes were prepared with N,N-dioctadecylmethylamine as H(+)-sensitive ionophore and pH calibration resulted in slopes of 55 mV decade-1 over a pH range from 11 to 6. OPH was isolated from recombinant Escherichia coli DH5 alpha and immobilized within poly(carbamoyl sulfonate) prepolymer on the surface of the H(+)-sensitive electrode without any further fixation membrane. OPH catalyzes the hydrolytic cleavage of OP compounds which releases protons in a concentration proportional to hydrolyzed substrate. Sensor performance was investigated with regard to enzyme load, concentration, pH and temperature of the measuring buffer using paraoxon as analyte. Best sensitivity and response time were obtained with sensors prepared with 250 U of OPH and measuring at 37 degrees C in 1.0 mM HEPES buffer, pH 9.3, containing 100 mM NaCl. The enzyme sensor exhibited a linear calibration range of 0.01-0.15 mM chlorpyrifos, 0.05-0.35 mM diazinon, 0.05-0.4 mM paraoxon and 0.007-0.05 mM parathion, respectively. For all these analytes response times to reach 95% of maximum change in potential did not exceed 5 min. Sensors stored under dry conditions at 4 degrees C still showed 60% of initial hydrolytic rate after 70 d. The sensors even when stored dry were ready for measurements after 5 min incubation in measuring buffer. A range of putative interfering substances did not influence sensor response, and suitability of measuring OPs in soil extracts was ascertained. PMID- 11219067 TI - A mediator-type biosensor as a new approach to biochemical oxygen demand estimation. AB - A novel biosensor for the determination of biochemical oxygen demand (BOD) was developed using potassium hexacyanoferrate(III) [HCF(III)] as a mediator. The sensor element consists of a three-electrode system, with both working and counter electrodes compactly integrated as a disposable using etching and electroplating processes. Pseudomonas fluorescens biovar V (isolated from a wastewater treatment plant) was immobilized on the surface of the working electrode using poly(vinyl alcohol)-quaternized stilbazol (PVA-SbQ) photopolymer gel. Synthetic wastewater described by the Organization for Economic Cooperation and Development (OECD) was used as a standard solution instead of glucose glutamic acid synthetic wastewater. The conditions of amperometric measurement were optimized at +600 mV (vs. Ag/AgCl) operating potential, namely 40 mM HCF(III) in a 0.1 M phosphate buffer (pH 7.0) at 20 degrees C. The sensor response was linear from 15 up to 200 mg O l-1 BOD. The response time was 15 min at 200 mg O l-1 BOD. To demonstrate the wide metabolic range of activity of the sensor, the sensor response to 14 substances in four categories of organic compounds was investigated. Further, it was shown that the response of this BOD sensor was not influenced in samples with low concentrations of dissolved oxygen under the measuring conditions used. For real wastewaters, the BOD values were determined using the sensor and compared favorably with those determined by the conventional BOD5 method. PMID- 11219068 TI - Bismetalloporphyrin-based ISE sensitive to fluoroborate. AB - Several mu-oxo-bismetalloporphyrin complexes were synthesized for preparing fluoroborate sensors. The electrode based on mu-oxo-bis[tetra(p chlorophenyl)porphinatomanganese(III)] with an optimized membrane composition shows a potentiometric response towards fluoroborate ion over the concentration range from 4.3 x 10(-7) to 1.0 x 10(-1) mol l-1 with a Nernstian slope, a wide working pH range from 5.5 to 12.0 and a fast response time of 30 s. The electrode shows anti-Hofmeister selectivity towards BF4- with respect to common co-existing ions, which is an improvement over methods reported so far. As electroactive materials, several mu-oxo-bismetalloporphyrins with different substituents on the benzene rings were compared for potentiometric response characteristics. The interaction between BF4- and bismetalloporphyrin was investigated using UV/VIS spectrophotometry. The electrode was applied to the determination of fluoroborate in electroplating solutions. PMID- 11219069 TI - Mathematical analysis for impedance change with proteolytic digestion of gelatin. AB - A mathematical analysis is proposed to demonstrate an inter-relationship between the proteolytic digestion of gelatin on the surface of an interdigitated gold electrode and the resulting rate of impedance change, at different collagenase concentrations, in a biosensor used to detect protease in solution. The impedance change due to digestion of the gelatin layer by collagenase for the overall digestion process was expressed in two different stages: an initial exponential period where the rate of impedance change with enzymic digestion was slow, leading to a critical thickness; after which there was a greater change in impedance associated with subsequent dissolution of the layer and partial or complete uncoating of the digits on the electrode surface. An inter-relationship between the rate of impedance change and collagenase concentration within the range 0.2-0.6 mg ml-1 was predicted for the early stages of the digestion process. A kinetic theory for the rapid rate of impedance change with collagenase concentrations could not be developed owing to the rate remaining almost constant for all concentrations of collagenase, after the critical thickness had been reached. An inter-relationship between the rate of impedance change and stirrer speed was also demonstrated. PMID- 11219070 TI - The enhanced electrogenerated chemiluminescence of Ru(bpy)3(2+) by glutathione on a glassy carbon electrode modified with some porphine compounds. AB - It has been found that the electrochemical activity of glutathione was increased greatly at the glassy carbon electrodes modified with 5,10,15,20 tetraphenylporphine ruthenium(II) carbenyl (RuTPP), meso-tetraphenylporphine copper(II) complex (CuTTP) and hemin. It has been also found that glutathione would enhance the electrogenerated chemiluminescence (ECL) of Ru(bpy)3(2+) at a hemin glassy carbon electrode; the enhanced ECL intensity was linear with the concentration of glutathione in the range of 1 x 10(-7)-1 x 10(-4) mol l-1, based on which method for determination of glutathione has been developed. The detection limit of glutathione was 2 x 10(-8) mol l-1, and the relative standard deviation for 1 x 10(-6) mol l-1 glutathione was 2.7%. The mechanism for this ECL system has been proposed. PMID- 11219071 TI - Study of the electrochemical behavior of mitoxantrone and its determination at a Co-C modified ultramicroelectrode. AB - In 0.005 mol dm-3 Tris-0.05 mol dm-3 NaCl buffer solution (pH 7.10), the electrochemical behavior of mitoxantrone was studied by linear-sweep voltammetry and cyclic voltammetry at a Co-carbon fiber ion implantation modified ultramicroelectrode. A sensitive reduction peak was obtained. The peak potential was -0.798 V (vs. SCE), the peak current was proportional to the concentration of mitoxantrone over the range of 2.0 x 10(-7)-6.0 x 10(6) mol dm-3 and the detection limit was 4.2 x 10(-8) mol dm-3. This method was applied to the direct determination of mitoxantrone in urine. Recoveries were in the range 95.4-105.8%. The reduction process was quasi-reversible with absorptive characteristics at a Co-C ultramicroelectrode. According to Laviron's theory, the electrode reaction rate constant ks and the electron transfer alpha of mitoxantrone were 4.4 s-1 and 0.48, respectively. The composition and depth distribution of elements on the surface of the Co-C ultramicroelectrode were determined by Auger electron spectroscopy. The experiments showed that Co was implanted into the surface of the carbon fiber, and the Co-C ultramicroelectrode had good stability and reproducibility. PMID- 11219072 TI - A PARAFAC algorithm using penalty diagonalization error (PDE) for three-way data array resolution. AB - A modified parallel factors analysis (PARAFAC) algorithm with the penalty diagnolization error (PDE) was developed. This algorithm can overcome the slow convergence problem of the traditional PARAFAC method and is insensitive to the number of components, i.e., it is much faster than PARAFAC and insensitive to overestimation of the dimensionality of the model. The characteristic performance was demonstrated by treating simulated and real excitation-emission fluorescence data for samples of naphthalene, 1-naphthol and 2-naphthol with satisfactory results. PMID- 11219073 TI - Polymorphic analysis of a pharmaceutical preparation by NIR spectroscopy. AB - A method for the characterization and determination of the crystalline from present in the amorphous miokamycin of a pharmaceutical preparation using near infrared spectroscopy (NIRS) is proposed. The study leading to the development of the proposed method involved both qualitative (classification by residual variance analysis) and quantitative aspects (the determination of both total miokamycin and its crystalline form using multivariate calibration). Samples containing less than 5% of the total amount of miokamycin in its crystalline form can be accurately classified. Partial least-squares regression (PLSR) allows low contents of the crystalline form to be determined with absolute errors less than 1.5%, which is comparable to the limit of detection of the X-ray diffraction technique used as reference. Also, the total miokamycin content is determined by NIRS with errors less than 1%. The simplicity, expeditiousness and robustness of the proposed method make it an effective tool for determining both total and crystalline miokamycin in solid dosage forms. PMID- 11219074 TI - Monitoring the melt-extrusion transesterification of ethylene-vinylacetate copolymer by self-modeling curve resolution analysis of on-line near-infrared spectra. AB - The transesterification of molten ethylene-vinylacetate (EVA) copolymers by octanol with sodium methoxide as catalyst in an extruder has been monitored by on line near infrared (NIR) spectroscopy. A total of 60 NIR spectra were acquired for 37 min with the last spectrum recorded 31 min after the addition of octanol and catalyst was stopped. The experimental spectra show strong baseline fluctuations which are corrected for by multiplicative scatter correction (MSC). The chemometric methods of the orthogonal projection approach (OPA) and multivariate curve resolution (MCR) were used to resolve the spectra and to derive concentration profiles of the species. The detailed analysis reveals the absence of completely pure variables which leads to small errors in the calculation of pure spectra. The initial estimation of a concentration that is necessary as an input parameter for MCR also presents a non-trivial task. We obtained results that were not ideal but applicable for practical concentration control. They enable a fast monitoring of the process in real-time and resolve the spectra of the EVA copolymer and the ethylene-vinyl alcohol (EVAL) copolymer to be very close to the reference spectra. The chemometric methods used and the decomposed spectra are discussed in detail. PMID- 11219075 TI - Spectrofluorimetric determination of moxifloxacin in tablets, human urine and serum. AB - A spectrofluorimetric method to determine the antibiotic moxifloxacin is proposed and was applied to pharmaceuticals, human urine and serum. The fluorimetric method allows the determination of 30-300 ng mL-1 moxifloxacin in aqueous solution containing phosphoric acid-phosphate buffer (pH 8.3) with lambda exc = 287 nm and lambda em = 465 nm. Detection and quantification limits were 10 and 30 ng mL-1, respectively, with a relative standard deviation (n = 10) of 2%. This method was applied to the determination of moxifloxacin in three Spanish commercial pharmaceutical formulations. Another variant of the method in micellar medium allows the direct measurement of moxifloxacin in human serum and urine by standard additions. The enhanced fluorescence of moxifloxacin in 8 mM sodium dodecyl sulfate (SDS) solution at pH 4.0 (acetic acid-acetate buffer) for lambda exc = 294 nm and lambda em = 503 nm shows the same linear range as the aqueous method with a 25% lower slope (with detection and quantification limits of 15 and 60 ng mL-1, respectively, and a relative standard deviation of 1.3%), but permits the background fluorescence for urine and serum blanks to be minimized. Hence, sufficient sensitivity is reached to determine therapeutic concentrations of the drug in urine (average recovery 102 +/- 2%) and serum (average recovery 105 +/- 2%) samples. PMID- 11219077 TI - Sensitive fluorimetric determination of formaldehyde by the co-quenching effect of formaldehyde and sulfite on the fluorescence of tetra-substituted amino aluminium phthalocyanine. AB - A novel and sensitive fluorimetric method was developed for the determination of formaldehyde based on the co-quenching effect of formaldehyde and sulfite on the fluorescence of tetra-substituted amino aluminium phthalocyanine. Formaldehyde in the concentration range 0.040-1.19 micrograms ml-1 can be determined with a limit of detection of 7.5 ng ml-1. The relative standard deviation for nine replicate measurements of 80.0 ng ml-1 formaldehyde is 1.8%. The method was applied to the analysis of real samples with satisfactory results. PMID- 11219076 TI - Determination of trace selenium in human plasma and hair with ternary inclusion compound-fluorescent spectrophotometry. AB - A method for determination of selenium in plasma and hair with ternary inclusion compound-fluorescent spectrophotometry has been developed. The determination of selenium in plasma and hair can be performed directly in aqueous solution. Blood and hair samples were destroyed by oxygen flask combustion. The linear range was 10-500 ng mL-1 for plasma and 10-100 ng mL-1 for hair. Within-day and day-to-day precisions for plasma ranged from 5.4% to 9.3% (n = 7) and from 3.5% to 14.5% (n = 7), respectively. Within-day precisions for hair ranged from 0.6% to 6.2% (n = 7). Recoveries ranged from 91.0% to 97.8% for plasma and from 95.0% to 102.0% for hair. The blood samples from 15 Hans and 20 Uygurs in Xinjiang Uygur automatic region and 23 Hans in Liaoning province were collected and determined. It was indicated that no statistically significant difference in plasma selenium concentration of the Hans between Xinjiang and Liaoning was found (F = 1.36, P > 0.05). However, there were statistically significant differences between the Hans and the Uygurs in Xinjiang (F = 1.01, P < 0.01) and between males and females in the two areas (P < 0.01). There was a low correlation between plasma selenium concentration and hair selenium concentration. The ratio of hair selenium concentration to plasma selenium concentration was 2.17, with a range of 1.63 2.88. PMID- 11219078 TI - Derivative spectrophotometry in the analysis of mixtures of phenols and herbicides. AB - Derivative spectrophotometry (zero-crossing technique) was applied to the determination of selected phenols and herbicides in two-component mixtures. Methyl- and chlorophenols (3-methylphenol, 2,3- and 3,4-dimethylphenol, 2,5-, 2,6 and 3,4-dichlorophenol and 2,4,5-trichlorophenol) and triazine, uracil and urea herbicides (simazine, propazine, hexazinone, bromacil and metoxuron) were examined. The RSD values ranged between 0.05 and 4% and the recoveries obtained were between 97 and 110%. The developed derivative spectrophotometric method was also applied as a complementary technique for the separation of overlapping peaks of sample compounds obtained by HPLC with diode-array detection. Metoxuron and 3 methylphenol, metoxuron and 2,5-dichlorophenol and simazine and 2,6 dichlorophenol were determined simultaneously by this method at the level of 1 x 10(-3) g l-1. PMID- 11219079 TI - Determination of titanium dioxide in foods using inductively coupled plasma optical emission spectrometry. AB - Titanium dioxide is a common food additive of increasing interest in dietary intake studies and dietary exclusion studies. Food labelling for titanium dioxide is imprecise so a method was developed for its rapid determination in foods using acid digestion and inductively coupled plasma optical emission spectrometry (ICPOES). Twenty-five foods thought to contain titanium dioxide were obtained. Based on preliminary digestion studies, samples (500 mg) were digested in 18 mol l-1 H2SO4 at 250 degrees C for 1 h and then diluted to 5.9 mol l-1 H2SO4 before determination of titanium by ICPOES at 336.121 nm. Emission intensity was suppressed by H2SO4 so standards were matched for acid concentration. Titanium dioxide embedded in gelatine was used to assess accuracy. A standard reference material of known titanium concentration and six foods of known titanium dioxide content were used as external reference materials. Limits of detection were 2-7.5 ppb, depending on spectral integration times, and the signal was linear up to 5 ppm. Results for all control samples were in good agreement with the expected values. Twelve of the foods contained detectable titanium, ranging from 0.001 to 0.782% by weight, but only eight indicated this on their labels, four being exempt under food labelling regulations. Based on food portion sizes, an individual's daily intake of titanium dioxide could exceed 200 mg from just one of these products. This method may facilitate future studies on titanium dioxide intake, given the present limitations of food labelling. PMID- 11219080 TI - Determination of metals in lubricating oils by flame atomic absorption spectrometry using a single-bore high-pressure pneumatic nebulizer. AB - The behaviour of a single-bore high-pressure pneumatic nebulizer (SBHPPN) as a tool for the analysis of lubricating oils by flame atomic absorption spectrometry (FAAS) was investigated. The effects of the sample oil content [from 10% to 100% (w/w) oil in 4-methylpentan-2-one, IBMK] and the carrier nature (IBMK and methanol) on the characteristics of the aerosols generated, on the analyte transport efficiency and on the analytical figures of merit in FAAS were studied. A pneumatic concentric nebulizer (PCN) was used for comparison. Increasing the oil content increases the viscosity of the sample. With the PCN this gives rise to coarser aerosols, making it impossible to nebulize samples with an oil content higher than 70% (w/w). Using the SBHPPN, the viscosity of the sample scarcely affects the characteristics of the primary aerosols. Hence, the SBHPPN is able, by using the appropriate carrier, to nebulize pure lubricating oils. Among the carriers tested, IBMK is the most advisable because it is fully miscible with all the oil samples. The SBHPPN provides higher sensitivities and lower limits of detection than the PCN. Compared with a method based on organic dilution, the use of the SBHPPN for the direct analysis of lubricating oils by FAAS makes it possible, in addition to increasing the analysis throughput, to detect elements at lower concentrations. Moreover, the SBHPPN provides similar results to those obtained using a previous acid digestion step. PMID- 11219081 TI - Thiosalicylic acid-immobilized Amberlite XAD-2: metal sorption behaviour and applications in estimation of metal ions by flame atomic absorption spectrometry. AB - Thiosalicylic acid (TSA)-modified Amberlite XAD-2 (AXAD-2) was synthesized by coupling TSA with the support matrix AXAD-2 through an azo spacer. The resulting chelating resin was characterized by elemental analyses, thermogravimetric analysis (TGA) and infrared spectra. The newly designed resin quantitatively sorbs CdII, CoII, CuII, FeIII, NiII and ZnII at pH 3.5-7.0 when the flow rate is maintained between 2 and 4 ml min-1. The HCl or HNO3 (2 mol l-1) instantaneously elutes all the metal ions. The sorption capacity is 197.5, 106.9, 214.0, 66.2, 309.9 and 47.4 mumol g-1 of the resin for cadmium, cobalt, copper, iron, nickel and zinc, respectively, whereas their preconcentration factor is between 180-400. The breakthrough volume of HCl or HNO3 for elution of these metal ions was found to be 4-8 ml. The limit of detection (LOD) for CdII, CoII, CuII, FeIII, NiII and ZnII was 0.48, 0.20, 4.05, 0.98, 1.28 and 3.94 micrograms l-1, respectively, and the limit of quantification (LOQ) was found to be 0.51, 0.29, 4.49, 1.43, 1.58 and 4.46 micrograms l-1, respectively. The loading half time, t1/2, for the cations was found to be less than 2.0 min, except for nickel for which the value was 13.1 min. The determination of each of these six cations is possible in the presence of other five, if their concentration is up to 4 times. All six metals were determined in river water (RSD approximately 0.7-7.7%) and tap water samples (RSD approximately 0.3-5.7%). The estimation of Co was made in the samples of multivitamin tablets (RSD < 2.3%). The results agree with those quoted by manufacturers. PMID- 11219082 TI - Development of an automated method for determining oil in water by direct aqueous supercritical fluid extraction coupled on-line with infrared spectroscopy. AB - A direct aqueous supercritical fluid extraction (SFE) system was developed which can be directly interfaced to an infrared spectrometer for the determination of oil in water. The technique is designed to provide an environmentally clean, automated alternative to established IR methods for oil in water analysis which require the use of restricted organic solvents. The SFE-FTIR method involves minimum sample handling stages, with on-line analysis of a 500 ml water sample being complete within 15 min. Method accuracy for determining water samples spiked with gasoline, white spirit, kerosene, diesel or engine oil was 81-100% with precision (RSD) ranging from 3 to 17%. An independent evaluation determined a 2 ppm limit of quantification for diesel in industrial effluents. The results of a comparative study involving an established IR method and the SFE-FTIR method indicate that oil levels calculated using an accepted equation which includes coefficients derived from reference hydrocarbon standards may result in significant errors. A new approach permitted the derivation of quantification coefficients for the SFE-FTIR analyses which provided improved results. In situations where the identity of the oil to be analysed is known, a rapid off line SFE-FTIR system calibration procedure was developed and successfully applied to various oils. An optional in-line silica gel clean-up procedure incorporated within the SFE-FTIR system enables the same water sample to be analysed for total oil content including vegetable oils and selectively for petroleum oil content within a total of 20 min. At the end of an analysis the SFE system is cleaned using an in situ 3 min clean cycle. PMID- 11219083 TI - A robust multisyringe system for process flow analysis. Part II. A multi-commuted injection system applied to the photometric determination of free acidity and iron(III) in metallurgical solutions. AB - A new software-controlled volume-based system for sample introduction in process flow injection analysis was developed. By using a multi-syringe burette coupled with one or two additional commutation valves, the multi-commuted injection of precise sample volumes was accomplished. Characteristics and performance of the injection system were studied by injecting an indicator in a buffered carrier. Three configurations were implemented in order to achieve two different tasks: the single injection of a sample in a two- or three-channels manifold, and the dual injection into different streams. The two channel flow system using the single injection was applied to the determination of free acidity in diluted samples containing high levels of iron(III), by employing the single point titration methodology. The precipitation of ferric hydroxide was prevented using the ammonium and sodium salts of oxalate and acetate as buffer titrant. Methyl Red was employed as indicator. The procedure allows determination of acid concentration in solutions with a Fe(III)/H+ molar ratio up to 0.2. Samples with higher Fe(III)/H+ molar ratios were spiked with a known strong acid at dilution. The three-channel configuration was applied to the determination of ferric ions, using, as reagent, a merging mixture of sulfuric acid and potassium thiocyanate. The double injection system was implemented in series in a single (three-channel) manifold in such a way that a different injection volume and a changed reagent were used for each analyte. It was applied to the separated or sequential determination of free acidity and ferric ions. In this configuration, iron(III) was determined using 0.5-0.7% (w/v) sodium salicylate solution as reagent. The systems can operate at up to 100, 84 and 78 injections per hour, respectively. Determinations on synthetic and process samples compared well with the reference values and procedures. Recoveries of 95-102% with a maximum RSD value of 5.4% were found for acidity. The respective values obtained for iron determinations were 96-105% and 4.3%. PMID- 11219084 TI - Sensitive determination of diquat by a kinetic method using the stopped-flow mixing technique. AB - A simple, sensitive, selective, fast and inexpensive assay for the determination of diquat is proposed. The method is based on the reduction of the herbicide to a strongly fluorescent monocation radical with sodium dithionite. The initial rate of this reaction is directly proportional to the diquat concentration. The stopped-flow mixing technique was used because the kinetic data can be obtained in only 7 s, meaning that the method can be automated. The calibration graph is linear over the range 5-500 ng ml-1 and the precision (RSD) is close to 1.2%. The applicability of the method was demonstrated by determining the herbicide in different kinds of samples. PMID- 11219085 TI - Flow injection analysis of fluoride: optimization of experimental conditions and non-linear calibration using artificial neural networks. AB - This paper deals with the application of artificial neural networks (ANNs) to two common problems in spectroscopy: optimization of experimental conditions and non linear calibration of the result, with particular reference to the determination of fluoride by flow injection analysis (FIA). The FIA system was based on the formation of a blue ternary complex between zirconium(IV), p methyldibromoarsenazo and F- with the maximum absorption wavelength at 635 nm. First, optimization in terms of sensitivity and sampling rate was carried out by using jointly a central composite design and ANNs, and a neural network with a 3 7-1 structure was confirmed to be able to provide the maximum performance. Second, the relationship between the concentration of fluoride and its absorbance was modeled by ANNs. In this process, cross-validation and leave-k-out were used. The results showed that good prediction was attained in the 1-4-1 neural net. The trained networks proved to be very powerful in both applications. The proposed method was successfully applied to the determination of free fluoride in tea and toothpaste with recoveries between 96 and 101%. PMID- 11219086 TI - Side-effects of dental materials reported in Scandinavian countries. AB - Dental treatment usually involves a wide range of materials which continue to grow in number and complexity. During the last decade there has been an increasing demand for safety evaluation and control of dental materials. Since it is the members of the dental staff who handle the materials in their most reactive states they constitute the main risk category. Bearing this in mind reported side-effects in both patients and dental personnel in Scandinavia are presented. Data from the only two existing national registers for side-effects of dental materials, i.e. those in Norway and Sweden, are thus elucidated. Furthermore, recent mainly Scandinavian publications dealing with the side effects of dental materials are presented. It can be concluded that a national register on the side-effects of dental materials, apart from revealing information regarding their frequency and nature, may detect changes in the profiles of adverse reactions and also serve as a tool for the post-marketing surveillance of dental materials. PMID- 11219087 TI - Surface composition and structure of titanium polished with aqueous slurry of ferric oxide. AB - Cast plates were prepared from commercial titanium. The plates were polished with a slurry of fine ferric oxide powder. The surface composition and structure were investigated by electron probe microanalysis (EPMA) and X-ray photoelectron spectroscopy (XPS). In the high pressure-polished surface, iron was non-uniformly distributed but oxygen was mostly uniformly distributed, while in a light pressure-polished surface, iron and oxygen were uniformly distributed though at lower and higher concentrations, respectively. EPMA state analysis and XPS suggested that the iron might exist as Fe2+ in the outermost surface, while it might be in a metallic state in the inner surface layer. PMID- 11219088 TI - Microfracture mechanisms of composite resins containing prepolymerized particle fillers. AB - The effect of prepolymerized particle fillers on fracture toughness of four commercial composite resins was studied. The ground surface morphology was examined with a field emission scanning electron microscope. Fracture toughness was determined by using single edge notched specimens. Acoustic Emission (AE), which is the elastic wave due to the release of energy from the localized sources of material, was detected by sensors of a high-sensitivity and low-noise resonance type during the fracture toughness test. Acoustic Emission signals detected were analyzed for parameters such as amplitude and energy. Fracture surfaces were examined with a scanning electron microscope. The fracture toughness values, AE releasing patterns during fracture toughness test, and the fracture surface findings were analyzed to understand the fracture behavior of composite resins containing prepolymerized particle fillers. A microfracture model and fracture mechanisms to increase the fracture toughness of this type of composite resins are proposed. PMID- 11219089 TI - Corrosion characteristics of ferric and austenitic stainless steels for dental magnetic attachment. AB - The corrosion behaviors of four ferric stainless steels and two austenitic stainless steels were examined in a simulated physiological environment (0.9% NaCl solution) to obtain basic data for evaluating the appropriate composition of stainless steels for dental magnetic attachments. The corrosion resistance was evaluated by electrochemical techniques and the analysis of released metal ions by atomic absorption spectrophotometry. The surface of the stainless steels was analyzed by X-ray photoelectron spectroscopy (XPS). The breakdown potential of ferric stainless steels increased and the total amount of released metal ions decreased linearly with increases in the sum of the Cr and Mo contents. The corrosion rate of the ferric stainless steels increased 2 to 6 times when they were galvanically coupled with noble metal alloys but decreased when coupled with commercially pure Ti. For austenitic stainless steels, the breakdown potential of high N-bearing stainless steel was approximately 500 mV higher than that of SUS316L, which is currently used as a component in dental magnetic attachments. The enriched nitrogen at the alloy/passive film interface may be effective in improving the localized corrosion resistance. PMID- 11219090 TI - Influence of different elastic moduli of dowel and core on stress distribution in root. AB - This study was carried out to investigate the influences of elastic moduli of the dowel-core combination on the stress distribution in the root by the use of 2 dimensional finite element analysis. The peak stress at the dowel-cement interface was influenced strongly by a change of elastic modulus of the post (from 20,000 kg/mm2 as a hard prefabricated post to 8,000 kg/mm2 as a custom cast post) for both vertical and 45 degree oblique loading (rho > 90%). Peak dentinal stress adjacent to the luting cement layer depended only on the post material for vertical loading (rho [symbol: see text] 99%). In contrast, the post and core materials (from 8,000 kg/mm2 as cast core to 300 kg/mm2 as composite resin core) acted in cooperation on the stress magnitude for oblique loading, but the influence of the core material was stronger than that of the post (rho of core [symbol: see text] 41% and rho of post [symbol: see text] 26%). On the other hand, at the marginal region the effect of the core material contributed more than 86% to the peak stress value for both loadings, and the post material affected at most about 11% of the bending resistance. PMID- 11219092 TI - Detection of bisphenol-A in dental materials by gas chromatography-mass spectrometry. AB - The xenoestrogenic substance bisphenol-A is widely used as a synthetic precursor of resin monomers, such as bisphenol-A diglycidyl methacrylate. Reports describing the release of bisphenol-A from polymerized resin into saliva have aroused considerable concern regarding exposure to xenoestrogen by dental treatment. The purpose of the present study was to demonstrate a reliable methodology of detecting the trace amounts of bisphenol-A in dental materials. Bisphenol-A was separable from bisphenol-A diglycidyl methacrylate, which is often employed as the principal dimethacrylate monomer, by selective extraction with a Sep-Pak C18 cartridge. Using this extraction method in combination with a gas-chromatography mass-spectrometry, we have obtained evidence that all unpolymerized materials used in this study were contaminated with bisphenol-A. Quantitative analysis using a deuterium-labeled compound as an internal standard revealed bisphenol-A contents in commercial dental materials ranging from < 1 microgram/g material to about 20 micrograms/g material. The polymerized dental materials released up to 91.4 ng bisphenol-A/g material into phosphate buffered saline during 24-h incubation. These results indicate that bisphenol-A can be released from dental materials, however the leachable amount would be less than 1/1000 of the reported dose (2 micrograms/kg body weight/day) required for xenoestrogenisity in vivo. PMID- 11219091 TI - Addition of antibacterial agents to MMA-TBB dentin bonding systems--influence on tensile bond strength and antibacterial effect. AB - To produce a bonding system which has both high bond strength and antibacterial properties, an antibacterial agent (vancomycin: VCM or metronidazol: MN) was added to the PMMA powder of 4-META/MMA-TBB resin (CB). The influence of the addition of an antibacterial agent on tensile bond strength to dentin and the antibacterial effect were investigated in this study. Forty-seven freshly extracted bovine first or second incisors were used to measure the tensile bond strength to dentin. The bond strengths to bovine dentin were not significantly decreased by addition of VCM (1%, 2%, 5%), or MN (1%) to CB (p < 0.05). The antibacterial effect of CB containing antibacterial agent on six strains of bacteria was investigated by the agar plate diffusion method, analyzing the appearance of the inhibition zone around a resin disk following anaerobic culturing. The resin disks containing VCM showed antibacterial effects on all of the strains examined; the widths of the inhibition zones were 4-15 mm. The resin disks containing MN showed antibacterial effects on three strains; the widths of the inhibition zones were 0-4 mm. It was thus possible to produce a bonding system with both antibacterial effect and high tensile bond strength by addition of VCM to PMMA powder. PMID- 11219093 TI - Application of high resolution microfocus X-ray CT for the observation of human tooth. AB - The calcification degree of extracted human teeth was observed by using high resolution microfocus X-ray CT. As samples, upper and lower first premolars extracted from a 21-year-old female were used. The computed tomograms were produced by high resolution microfocus X-ray CT with a open vacuum X-ray source, rotating sample stage, and image sensor. The distinction between enamel and dentin was very clear, and the shape of the pulp cavity was also clearly identified. The secondary dentin was visible in the circumpulpal dentin. The color map displays showed the heterogeneity of the calcification degree not only in the dentin but also in the enamel. The enamel was divided into three layers according to the calcification degree. High resolution microfocus X-ray CT was very useful for the observation of the internal structure of human teeth without destroying the samples. PMID- 11219094 TI - Elution of bisphenol A from composite resin: a model experiment. AB - To understand the leaching characteristics of bisphenol A (BPA) from composite resins, we prepared experimental composite resins containing known amounts of BPA and examined the BPA elution from the resins in water and methanol at 37 degrees C. The concentration of BPA in each eluate was determined by high performance liquid chromatography. Cumulative BPA release was calculated and plotted against extraction time. The elution of BPA was rapid during a 6-hr period for both solvents, and then declined and continued steadily. Plots of square root of the amount of BPA leached against logarithm of extraction time produced good linear relationships from a 6-hr period thereafter. Extrapolation of the relationship enabled prediction of the amount of BPA to be leached in the long term. The present results suggested that little or no estrogenic effect due to long-term elution of BPA from commercial Bis-GMA-based resins is expected in practice. PMID- 11219095 TI - Acid and base-catalyzed hydrolysis of bisphenol A-related compounds. AB - In order to ascertain whether an estrogenic bisphenol A is produced from bisphenol A-related monomers by chemical-induced hydrolysis and to clarify their hydrolytic mechanisms, bisphenol A dimethacrylate (Bis-DMA) and bisphenol A bis(glycidyl methacrylate) (Bis-GMA) were reacted with phosphoric acid, hydrochloric acid, and sodium hydroxide in methanol or methanol/water mixed media at 37 degrees C. Amounts of monomethacrylate intermediates as well as bisphenol A (BPA) were determined by the use of high-performance liquid chromatography (HPLC), and time-conversion curves of hydrolytic products were prepared. BPA and bisphenol A monomethacrylate were produced by acid-catalyzed hydrolysis of Bis DMA. Bis-GMA was partly converted into monomethacrylate by phosphoric acid and into monomethacrylate and 2,2-bis[4-(2,3-dihydroxypropoxy) phenyl]propane (BHP) by hydrochloric acid. Hydrolytic reactions by sodium hydroxide were completed almost within 1 day, resulting in the production of BPA from Bis-DMA, and BHP from Bis-GMA. No BPA was formed from Bis-GMA by chemical-induced hydrolysis. The hydrolytic behaviors of these monomers were discussed. PMID- 11219096 TI - Effect of the adhesive layer thickness on the fracture toughness of dental adhesive resins. AB - We investigated how the thickness of an adhesive layer between two Co-Cr alloy plates affected the mode I fracture toughness of dental adhesive resin by varying the type of resin using a double cantilever beam (DCB) test. Two typical adhesive resins (PV and SB) were used. The adhesive layers of the DCB test specimens were 20, 100 and 200 microns thick. The fracture modes of PV differed with the thickness of the adhesive layer, such as interface fracture at 20 microns thickness, and similar cohesive fracture at 100 and 200 microns thickness. In the case of SB, crack-propagating areas were observed as cohesive fractures in all test specimens with different adhesive layer thickness, and the surfaces of these areas became remarkably rougher as the thickness of the adhesive layer increased. The fracture toughness of PV was not affected by the differences in thickness between the 100 and 200 microns adhesive layers, but there was a notable decrease in fracture toughness when the adhesive layer decreased to a thickness of 20 microns. That of SB showed a tendency to increase as the adhesive layer became thicker. PMID- 11219097 TI - New initiation system for resin polymerization using metal particles and 4-META. AB - Fifteen kinds of metal particles were examined to establish whether they could induce the setting of UDMA-based monomer containing BPO without amine under the presence of 4-META at room temperature. FT-IR spectra of the resultant set samples and the monomer were analyzed to see if the setting was caused by the polymerization. The effects of 4-META and BPO concentrations on the setting time were also studied using the metal particles that induced the setting very effectively. As-received Cu, Zn, Mo, Sn, Co, and In particles could initiate the polymerization of the monomer in combination with BPO and 4-META when they were moistened with water. All the three kinds of silver alloy particles examined also could initiate the polymerization, although pure silver metal particles could not. The presence of 4-META drastically shortened the setting time of the mixture of Cu particles and the monomer containing BPO, while higher concentration of BPO in the monomer significantly shortened the setting time. PMID- 11219098 TI - Polymerization of UDMA using zinc particles and 4-META with and without BPO. AB - The polymerization phenomena of zinc particles moistened with a small amount of water, 4-META, and UDMA without amine in the presence and absence of BPO were investigated. The effects of 4-META and BPO on the setting time and the degree of conversion (DC) were studied. Moreover, the effect of zinc ion amount on the setting time was investigated. As-received zinc particles could induce the polymerization either with or without BPO. A higher concentration of 4-META shortened the setting time and increased DC when BPO was absent. However, the presence of BPO generally retarded the setting time and decreased DC, although its effect was dependent on the 4-META concentration. A higher amount of zinc ion retarded the setting reaction in the presence of 4-META. The zinc particles mixed with 10% zinc sulfate and acetic acid solutions could induce the polymerization of UDMA containing BPO when the amine and 4-META were absent. PMID- 11219099 TI - Development of metal-resin composite restorative material. Part 3. Flexural properties and condensability of metal-resin composite using Ag-Sn irregular particles. AB - Powder-liquid type metal-resin composites, using Ag-Sn irregular particles as the filler, 4-META as coupling agent and UDMA + TEGDMA as resin matrix, were experimentally prepared under 9 different conditions (three different particle sizes and three different filler contents). The flexural strength and flexural modulus were measured. Three different irregular particle size MRCs without redox initiator at 94% filler content, as well as amalgam, conventional hybrid composite and Ag-Sn spherical particle MRC were evaluated for condensability. The flexural strength of the Ag-Sn irregular particle MRC was significantly influenced by both the filler particle size and filler contents (p < 0.01). It increased when either the filler content increased or the particles size decreased. The highest flexural strength (97.6 MPa) was obtained from the condition of particles size < 20 microns and 94% filler content. The flexural modulus was significantly influenced by filler content and it increased with increasing filler content. The condensability of the Ag-Sn irregular particle MRC was lower than that of amalgam but much higher than presently available conventional composites and spherical particle MRC. PMID- 11219100 TI - Genetic potential of interfacial guided osteogenesis in implant devices. AB - The purpose of this review is to summarise recent advances in the design and composition of bioactive surface layers of implantabile biomaterials, and thus the genetic potential of osteoprogenitor cells to recognize and respond to these diverse implanted biomaterials. Changes applied to a biomaterial's surface, in general, could improve its biocompatibility, osseointegration and durability properties, which are required for long-term implantation in the living body. In this review, the implant-bone interface was evaluated and interpreted on the basis of osteoblast cell cultures, i.e., on the genetic potential of osteoblasts to express different phenotype markers depending on the type of biomaterials used. The interface formed by in vitro-grown osteoblasts may be used to identify components of the in vivo implant-bone interface. Over the years, a large number of implant systems consisting of many different biomaterials have been introduced in dentistry and orthopaedics. This paper discusses the performance of currently used metals and other biomaterials, by focusing on the events which occur immediately after implantation and on their impact on the bone-implant interface. The review demonstrates that continuous improvements in composition, surface modality and design of implants may benefit osseointegration and clinical longevity of such implants. No load-bearing conditions or clinical status are discussed. Titanium (Ti) and calcium phosphate ceramics are regarded as the most biocompatible synthetic substances known to be used in hard tissue implantation. These biomaterials are osteoconductive, and do not induce ectopic bone formation. Nonetheless, they provide a physical matrix which is suitable for the deposition of new bone and may guide both the growth and extension of the bone. Comparative investigation evaluated that Ti implant systems appear to be apposed by more bone than ceramic systems, although alternatives concerning the type of Ti alloy and bioactive surface layer engineering, generate extremely diverse osseointegration results. Manufacturers have created an extensive range of inorganic or ceramic coatings on Ti implants in order to achieve better bone healing and osteoconduction. Biologically active molecules, added to the implant surface, represent breakthroughs in guided interfacial osteogenesis. This methodology offers an enormous potential of genetic controlling and promoting osteogenesis. The bone growth factors are not fully understood, but most researchers agree that the contact between the bioactive surface layer of the implant and bone is not static but dynamic and that the above factors may maximise the implant osseointegration. PMID- 11219101 TI - [The bone and joint decade]. PMID- 11219102 TI - [The motivated conversation]. PMID- 11219103 TI - [Investigation of demented patients. New possibility for improved quality in cooperation between general practice and hospitals]. PMID- 11219104 TI - [Echinococcus multifocal. Epidemiology, clinical findings and treatment]. AB - Infection with the fox dwarf tapeworm, Echinococcus multilocularis, has for the first time been found in a fox in Denmark, and E. multilocularis infection is therefore now a possible diagnosis in Danish patients. This paper reviews the life cycle, epidemiology, clinical symptoms, diagnosis, and treatment of E. multilocularis infections. PMID- 11219105 TI - [Can ultrasonography replace arteriography in arteriosclerosis of the lower limb?]. AB - Arteriography is the imaging modality of choice before lower limb revascularization, because it allows pinpointing of the diseased arteries and planning of the treatment strategy, be it PTA or bypass grafting. However, a 2-3% risk of complications, makes assessment of non-invasive alternatives mandatory. Insufficient contrast filling of infrapopliteal arteries distal to severe lesions have also challenged the status of arteriography as the gold standard before revascularisation. The use of duplex arterial mapping is a promising alternative, as it has the highest agreement in the femoral segment and the lowest in the infra-popliteal segment. Duplex arterial mapping is a reliable means of predicting whether patients will require a bypass graft or an endovascular procedure, and, if surgery is required, in predicting the actual location of both anastomoses. PMID- 11219106 TI - [Risk factors for low back pain among 1.389 pupils in the 8th and 9th grade. An epidemiologic study]. AB - INTRODUCTION: The aim of this study was to investigate the frequency and severity of low back pain (LBP) in 13-16-year-old pupils in relation to selected factors, such as anthropometry, physical activity, smoking, hypermobility, and tightness of hamstring muscles. METHODS: The study was designed as a cross-sectional questionnaire-based survey and all the pupils were examined by the school doctor for height, weight, mobility of joints, and general health status. RESULTS: The lifetime prevalence of non-specific LBP was 58.9% and the one-year prevalence was 50.8% with no differences between the sexes. Recurrent/continuous LBP in a moderate to severe degree was recorded in 19.4% of the school children (182 F, 88 M). This was positively correlated to a female gender, a BMI of more than 25 kg/square meter, competitive sports for boys, poor physical fitness, daily smoking, heavy jobs in leisure time, increased use of the health system, and reduced life quality. DISCUSSION: Stepwise logistic regression analysis indicates that a female gender, daily smoking, and heavy jobs are important associated factors for severe LBP in adolescents, with an observed probability of 46% if all factors are present. We do not know yet whether these factors have any causal importance for the development of severe LBP. PMID- 11219107 TI - [Glucagon-like peptide 2, a neurotransmitter with a newly discovered role in the regulation of food ingestion]. AB - We report here that glucagon-like peptide 2(GLP-2) and its receptor constitute a distinct projection system connecting the nucleus of the solitary tract with the dorsomedial hypothalamic nucleus (DMH). The DMH contains a dense plexus of GLP-2 immunoreactive fibres and is the only hypothalamic nucleus expressing GLP-2 receptor mRNA. Consistent with this, central application of GLP-2 activates the expression of neurones solely in the DMH. Furthermore, central administration of GLP-2 causes a dose-related, a pharmacologically and behaviourally specific inhibition of food intake in rats. Surprisingly, the alleged GLP-1 receptor antagonist, Exending (9-39), proved a functional antagonist of centrally applied GLP-2. These data implicate GLP-2 as an important neurotransmitter in the regulation of food intake and likely bodyweight. Our data therefore point to the DMH as a crossroad for endocrine and visceral information affecting feeding behaviour. PMID- 11219108 TI - [Laparoscopic fundoplication. A prospective assessment of 100 operations for gastroesophageal reflux]. AB - INTRODUCTION: Laparoscopic fundoplication was assessed in a prospective study. METHOD: One hundred patients with gastroesophageal reflux (GORD) were treated by a 360 degrees fundoplication. The number of operations completed as a laparoscopic procedure, the complication rate, the length of hospital stay and time of work and the effect on GORD symptoms were used as endpoints. RESULTS: The operations could be performed as a laparoscopic procedure in 97 cases. Complications were few: A left-sided pneumothorax in two patients. Median operating time was 100 min and postoperative hospital stay two days. Sufficient reflux control was obtained in 93 patients. Only minor side effects were encountered in three patients (dysphagia two, flatulence one). At three-month control 91 were satisfied. After 3-49 mo (median 19 mo) two have needed a re operation for dysphagia (one due to tight suture and one for a rotated fundoplication). One patient had the fundoplication taken down for embarrassing flatulence in spite of successful reflux control. CONCLUSION: Laparoscopic fundoplication offers a good immediate control of GORD during a short hospitalization with few complications or side effects. No long term results are available at present. PMID- 11219109 TI - [Endogenous retroviruses in multiple sclerosis]. AB - INTRODUCTION: In recent years, it has been suggested that human endogenous retroviruses (HERVs) may play a role in autoimmune diseases. HERVs represent both putative susceptibility genes and putative pathogenic viruses in multiple sclerosis (MS). Initially, our objective was to characterize a retrovirus produced by MS derived cell lines and to investigate this association in vivo. METHODS: The retrovirus was identified by RT-PCR on virion RNA purified from RT positive retroviral particles from the MS cell lines, and from blood samples from MS patients. Wistar rats were immunized with purified virions and serological responses analyzed by ELISA. RESULTS: Sequence variants highly homologous to the HERV-H family were found. The same sequences were specifically found in the particulate fraction of a series of MS patient plasma samples and were absent in controls. A database search demonstrated HERV-H copies in several chromosome regions implied in MS susceptibility. Virion-immunized rats developed a specific serological response towards HERV-H peptides indicating that immunogenic virion proteins are encoded by HERV-H. DISCUSSION: Activation of normally replicatively quiescent HERVs may be causally involved in MS. PMID- 11219110 TI - [Malignant neuroleptic syndrome or serotonergic syndrome]. AB - The malignant neuroleptica syndrome (MNS) and the serotonin syndrome (SS) can be impossible to differentiate. This case history describes clinical symptoms compatible with either MNS or SS in a 59-year-old schizophrenic male patient, who had been heavily medicated with antipsychotics for several years in close relation to initiation of new treatment with a SSRI compound. The case shows that it is important to have both syndromes in mind when chronically ill patients are treated with several medicaments. PMID- 11219111 TI - [Picture of the month: aspiration of a foreign body]. PMID- 11219112 TI - [Drug therapy of heart insufficiency guided by hormone measurements]. PMID- 11219113 TI - [What does the FRISC II study say about the treatment of unstable coronary disease, especially non-Q-wave myocardial infarction?]. PMID- 11219114 TI - [Name confusion]. PMID- 11219115 TI - [Chronic subdural hematoma as a differential diagnosis to apoplexy]. PMID- 11219116 TI - Standards in evidence. PMID- 11219117 TI - The working practices of the police in relation to mentally disordered offenders and diversion services. AB - A research study was undertaken to examine the working practices of four bridewells in Hampshire in relation to mentally disordered offenders (MDOs) and diversion services. A consecutive sample of individuals detained in cells and not identified by the police as having a mental disorder were screened for the presence of mental disorder and their suitability for diversion. Custody and detention staff were observed and interviewed to elicit their views and working practices in relation to MDOs. The findings revealed that in bridewells with diversion schemes an average of about 7% of detained individuals had mental disorders who were suitable for diversion but were not detected by the police. In the bridewell without a diversion scheme the figure was 14%. Conversely, many individuals without a formal mental disorder were inappropriately referred to diversion schemes. The effectiveness of screening processes by custody staff was variable. Facilities in the bridewells were not suitable for containing disturbed individuals. Delays in obtaining mental health assessments caused considerable concern for police officers and prolonged the discomfort of vulnerable individuals. Further preparation and training of custody staff is needed to improve screening procedures. Reception and detention facilities for mentally disordered individuals should be reviewed and response times for approved social workers (ASWs) and psychiatrists would benefit from improvement. PMID- 11219119 TI - Medical help-seeking by motor vehicle accident claimants. AB - The assessment of general psychiatric damages in personal injury cases is partly determined by evidence that the claimant has attempted to mitigate their losses by seeking medical help. However, there is no evidence that seeking medical help for a psychiatric injury is typical behaviour. The general practice consultation behaviour of 100 claimants with chronic physical and psychiatric injury with an onset at the time of a motor vehicle accident, was assessed over a 12-month period after the injury. GP consultations for physical and psychiatric symptoms were compared. At 12 months after the accident 53 (95% CI 42.7, 63.3) had consulted their GP with psychiatric symptoms and 94 (95% CI 88.8, 99.2) had consulted their GP with physical symptoms. Neither the sex, age or a pre-accident history of help-seeking for psychological symptoms was significantly predictive of post-accident help seeking for psychiatric injury. The results from this study provide information about the weight that should be given to medical help-seeking as a factor in assessing the value of claims for general psychiatric damages in personal injury cases. PMID- 11219118 TI - Pedestrian deaths following collisions with heavy goods vehicles. AB - Pedestrian fatalities following collisions with heavy goods vehicles ('lorries') in south-east Scotland were studied between 1992 and 1998. Data sources included police and ambulance reports, forensic medicine records, hospital casenotes and the Scottish Trauma Audit Group database. All injuries were scored according to the Abbreviated Injury Scale, yielding Injury Severity Scores (ISS). Sixteen pedestrians (mean age 60.2 years) died after being hit by a lorry. Actions of pedestrians were implicated in causing all the collisions--four of which appeared to be suicides. Four of the apparently accidental deaths involved pedestrians with significant blood alcohol levels. Thirteen pedestrians were dead when found. Ten pedestrians had an ISS of 75, having a total of 13 injuries acknowledged to be unsurvivable (Abbreviated Injury Scale = 6), largely to the head and chest. The unsurvivable injuries reflect huge forces, explaining why only a small proportion of the pedestrians survived to hospital. There is little potential to reduce the number of deaths by improving hospital treatment, rather the focus needs to be directed towards injury prevention. Although pedestrians appeared to be responsible for the collisions, the results suggest it may be more feasible and effective to direct injury prevention measures towards lorry drivers. PMID- 11219120 TI - Early outcomes of supervised discharge. AB - We have previously described the generally positive initial experiences of Supervised Discharge (SD) in a large Mental Health Trust serving a mixed inner city, suburban and rural population. This paper seeks to extend our earlier findings by reporting a longitudinal cohort study examining hospitalization before and after SD for the original sample. The main outcome measures were: renewal of SD; time spent out of hospital; survival to readmission or the end of the study period (1 April 1999). Of the 22 patients commenced on SD orders between April 1996 and October 1997, by 1 April 1999: 12 patients were still subject to supervised discharge; 15 had not been readmitted to hospital; survival out of hospital was longer--717 days, compared with 607 days in the same period before SD (p = 0.037); survival to readmission was also longer than before SD (p = 0.023). Contrary to early professional expectations patients subject to SD seem to survive for longer periods in the community. Although not always effective, its wider use should at least be considered as part of the care package for detained patients with a history of non-compliance with care packages leading to relapse and readmission. PMID- 11219121 TI - Trends in admissions to a regional secure unit (1983-1997). AB - Admissions and discharges from a 30-bed regional secure unit (RSU) were surveyed over a 15-year period. In the last five years there has been a significant increase in the average length of stay of patients and a marked decrease in the number of admissions and discharges. The reasons for this 'silting up' of the RSU by longer-term patients and the consequences for an effective forensic psychiatric service are discussed. PMID- 11219122 TI - Sudden death and intussusception in infancy and childhood--autopsy considerations. AB - Search of the autopsy files of the Department of Histopathology at the Women's and Children's Hospital (WCH), Adelaide, Australia for cases of intussusception from January 1961 to December 1995 revealed two deaths due to intussusception out of a total of 4,384 autopsies (0.05%). Both cases occurred in infants (aged five months and six months respectively) who had only non-specific and apparently minor manifestations of illness, until precipitate deterioration occurred. The intussusceptions were ileo-ileal and ileocaecal in location, respectively. A total of 204 cases of intussusception were found in a search of 28,123 surgical pathology cases (0.73%) at the WCH over the 20-year period from 1976 to 1995. Mesenteric lymphadenopathy was found in 16 cases (including one with possible Yersinia infection), Meckels diverticulum in 14, isolated gastric/pancreatic heterotopia in two, cystic fibrosis in two and Henoch-Schonlein purpura in one. Although it has been shown that unexpected death is more likely to occur in older children with purely small intestinal intussusception, the current cases demonstrate that unexpected death may occur at any age, with intussusception at any level. The autopsy assessment of deaths due to intussusception requires careful evaluation of cases for evidence of local or systemic disease, particularly given the hereditary nature of certain predisposing conditions. Careful review of the presenting history is also required to assess the quality of care received by the child in the time preceding death. PMID- 11219124 TI - Fit to be interviewed by the police--an aid to assessment. AB - The assessment of a suspect's fitness to be interviewed by the police is becoming an increasingly important part of a police surgeon's workload. This paper discusses the assessment in terms of the various factors that may render a person prone to providing an involuntary or false confession and proposes an aide memoire to assist the examining doctor. PMID- 11219123 TI - Death of a psychiatric patient during physical restraint. Excited delirium--a case report. AB - We report the case of a young man with a diagnosis of paranoid schizophrenia and multiple drug abuse who died in hospital following a period of prolonged physical restraint. The literature is reviewed, possible factors contributing to death discussed and measures which may reduce the incidence of such deaths in the future highlighted. PMID- 11219125 TI - Arsonists in maximum security: mental state at time of firesetting and relationship between mental disorder and pattern of behaviour. AB - Seventy-nine arsonists were identified in a Special Hospital. Sixty-eight had a clinical interview which included an analysis of symptoms present at the time of the most recent fire. Mentally ill arsonists did not differ from Psychopathic Disorder arsonists in their self-report of symptoms at the time of firesetting, the major difference was in the time course of their behaviour. Mentally ill arsonists lit their first fire on average eight years later than did Psychopathic Disorder patients. Further analysis indicates that PD women have a distinct group of current symptoms and behaviours. PMID- 11219127 TI - Survey of the use of the interim hospital order in Scotland (1985-94). AB - A retrospective case note review was undertaken of all admissions to the State Hospital under an Interim Hospital Order between 1985 and 1994 (n = 73). This represented 89 per cent of all Interim Orders made by the Scottish courts during this time period. Thirty-one per cent of patients received a non hospital disposal at the end of the assessment. Seventy-eight per cent of the interim hospital orders were for a period of three months of less. The demographic, illness and offense backgrounds of the group is presented. In addition, the outcome of the assessment is discussed in the light of current legislative changes. PMID- 11219128 TI - The place and point of 'true crime'. PMID- 11219126 TI - A prospective study using the Monroe Dyscontrol Scale as a measure of impulsivity in referrals to a forensic psychiatry service. AB - Many people referred to a forensic psychiatry service will have displayed impulsive aggression. There are few validated tests to allow a quantitative measurement of such behaviour. The Monroe Dyscontrol Scale (MDS) arose from work that recognized certain symptoms in people who had impulsive aggression, the so called 'episodic dyscontrol syndrome'. This study uses the MDS in two groups of people who were referred to a forensic psychiatry service. One was a group of 'mentally disordered' in-patients, and the other comprised consecutive referrals to the service. The groups were compared and certain features noted. The most interesting feature was that a family history of epilepsy was common, and associated with high scores on the MDS. The value of the MDS, and the importance of a family history of epilepsy, are discussed. PMID- 11219129 TI - Cutaneous burns from CS incapacitant spray. AB - A case of a superficial burn following exposure to CS incapacitant spray is reported. This is followed by a summary of the properties and effects of CS and the other agents which occur in the incapacitant spray. CS is relatively safe, but it does have unwanted effects, especially on skin exposure. Possible contributing factors to the production of a skin burn are discussed. PMID- 11219130 TI - Two cases of death due to plastic bag suffocation. AB - Deaths due to plastic bag suffocation or plastic bag asphyxia are not reported in Malaysia. In the West many suicides by plastic bag asphyxia, particularly in the elderly and those who are chronically and terminally ill, have been reported. Accidental deaths too are not uncommon in the West, both among small children who play with shopping bags and adolescents who are solvent abusers. Another well known but not so common form of accidental death from plastic bag asphyxia is sexual asphyxia, which is mostly seen among adult males. Homicide by plastic bag asphyxia too is reported in the West and the victims are invariably infants or adults who are frail or terminally ill and who cannot struggle. Two deaths due to plastic bag asphyxia are presented. Both the autopsies were performed at the University Hospital Mortuary, Kuala Lumpur. Both victims were 50-year old married Chinese males. One death was diagnosed as suicide and the other as sexual asphyxia. Sexual asphyxia is generally believed to be a problem associated exclusively with the West. Specific autopsy findings are often absent in deaths due to plastic bag asphyxia and therefore such deaths could be missed when some interested parties have altered the scene and most importantly have removed the plastic bag. A visit to the scene of death is invariably useful. PMID- 11219131 TI - The reconstruction: a useful tool in forensic sciences. AB - The intervention of a forensic pathologist may be required at any stage of a judicial investigation. Clearly, he or she plays an important role at a crime scene and later on during the examination of the body. But the forensic pathologist's contribution is equally important during reconstruction, which is most frequently called for in cases of violent deaths, homicides in particular. However, reconstruction may also be very useful in cases of less importance in terms of criminal law. It requires little investment and can provide precious evidence. In the two cases presented here we were able to exclude, respectively, the presumption of the adulteration of a blood sample taken for alcohol dosage and the accidental origin of an attempted murder. In fact, reconstruction may be a valuable procedure in any event requiring the participation of a forensic expert. PMID- 11219132 TI - Deaths among psychiatric patients: future considerations. PMID- 11219134 TI - [Ehlers-Danlos syndrome associated with acute pancreatitis]. AB - Ehlers-Danlos syndrome is an inherited connective tissue disease characterized by articular laxity, hyperelastic skin and tissue fragility. The syndrome is genetically, biochemically and clinically heterogeneous and several well-defined subtypes have been identified. We describe a patient with the type IV variant of this syndrome who developed acute spontaneous pancreatitis. PMID- 11219133 TI - [Assessment of the PCR-Southern blot technique for the analysis of viremia in patients with acute hepatitis A]. AB - Assessment of viremia in hepatitis A virus (HAV) infection is not frequently performed with conventional methods because the techniques used are laborious, have low sensitivity are usually performed in feces. The aims of this study were to develop a polymerase chain reaction (PCR) and Southern blot technique to detect HAV-RNA in the serum of patients with acute HAV infection and to determine the relationship between HAV-RNA and anti-HAV IgM and alanine aminotransferase (ALT) levels. The presence of HAV-RNA was studied in 26 serum samples from 21 patients with acute hepatitis A. We also studied 11 samples from patients with acute hepatitis B and 15 samples from patients with non-A, non-E hepatitis. HAV RNA was detected in 10 (38%) of the 26 serum samples from patients with acute hepatitis A. Simple PCR was positive in 5 samples and PRC-Southern blot was positive in 10. All the serum samples obtained during the first week of onset were HAV-RNA positive and 50% of those obtained during the second week were positive. None of the serum samples obtained after the second week of onset were HAV-RNA positive. None of the serum samples from the 11 patients with acute hepatitis B or from the 15 patients with non-A, non-E acute hepatitis were positive for HAV-RNA. No significant relationship was detected between HAV-RNA detection and an IgM anti-HAV or ALT positive result. In conclusion, the presence of HAV-RNA in acute hepatitis A is frequent but the PCR Southern blot technique is required for detection, which is transitory during the first weeks after onset. PMID- 11219136 TI - [The intestinal brain]. PMID- 11219135 TI - [Macromolecular creatinine kinase in patients diagnosed with ulcerative colitis]. AB - Macromolecular creatinine kinase (macro-CK) type 1 is a macroenzyme formed by the union of an immunoglobulin with a creatinine kinase (CK) enzyme. Its presence in the blood may lead to misdiagnosis of heart disease. This macromolecule has been described in various diseases and is relatively more frequent those with autoimmune etiology. We describe three cases of ulcerative colitis that presented elevated MB-isoenzyme of CK activity greater than the total CK quantified by the immunoinhibition method. Electrophoresis revealed an atypical band that corresponded with the presence of a type 1 macroenzyme. Detection of this macromolecule could be useful in cases of ulcerative colitis when results of blood testing lead to suspicion of ischemic disease. PMID- 11219137 TI - [Clinical approach for the patient requiring non-steroid anti-inflammatory agents: role of COX-2 inhibitors]. PMID- 11219138 TI - [Consensus on spontaneous bacterial peritonitis in liver cirrhosis: diagnosis, treatment, and prophylaxis]. PMID- 11219139 TI - [Fulminant infection caused by varicella herpes zoster in patient with Crohn disease undergoing treatment with azathioprine]. PMID- 11219140 TI - [Multifocal hepatic steatosis and Crohn disease]. PMID- 11219141 TI - [Helicoidal CT and choledocholithiasis]. PMID- 11219142 TI - [Efficacy of fecal detection of Helicobacter pylori with the HpSA technique in patients with upper digestive hemorrhage]. AB - BACKGROUND: The rapid urease test is the most commonly used test in the diagnosis of Helicobacter pylori infection in patients with upper gastrointestinal hemorrhage. However, some studies have suggested that results of this test are frequently false negative when blood is present. An effective new enzyme immunoassay for determining H. pylori antigens in stools has recently begun to be used. AIM: To determine the efficacy of the H. pylori stool antigen test (HpSAT) in patients with upper gastrointestinal hemorrhage. PATIENTS AND METHODS: Thirty two patients with upper gastrointestinal hemorrhage were prospectively studied from November 1998 to April 1999. In all patients the following tests were performed in the first 72 hours after onset of bleeding and 24 hours after hospital admission: upper gastrointestinal endoscopy, biopsy samples for the rapid urease test and histological study, blood samples for serology, stool samples for HpSAT, and the 13C urea breath test. Criteria for infection was a positive result in at least two of the four diagnostic techniques, except in the case of HpSAT. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS: Of the 32 patients, 23 (71.8%) were infected. The results of four HpSAT (12.5%) were negative and 28 were positive (87.5%). HpSAT showed high sensitivity (95.6%) but low specificity (33.3%). The PPV and NPV were 78.5% and 75% respectively. Of the 32 HpSAT, 25 (78.1) were performed in melenic stools: 22 were positive and 3 were negative. Seventy-five percent of negative HpSAT and 78.5% of positive HpSAT corresponded to melenic stools. CONCLUSIONS: HpSAT is a rapid, non-invasive technique that does not appear to be influenced by the presence of blood. Consequently, it can be applied in patients with upper gastrointestinal hemorrhage. The rapid urease test showed high sensitivity, specificity and PPV and should remain the first line test in patients with upper gastrointestinal hemorrhage. HpSAT is appropriate as a second-line technique and is useful when the rapid urease test is negative and infection is strongly suspected, when no samples for the rapid urease test have been taken and when endoscopy cannot be performed. The result obtained in the present study should be confirmed in future studies with larger samples. PMID- 11219143 TI - [Tolerance to and colon cleansing with 2 preparations. Polyethylene glycol or sodium phosphate]. AB - OBJECTIVE: To compare colon cleansing and tolerance with two preparations: polyethylene glycol 4-liters (PEG) and sodium phosphate (FS). MATERIAL AND METHODS: Prospective randomized study of 100 consecutive patients who underwent endoscopy after taking PEG (Bohm lavage solution) or FS (Fosfosoda). All patients were evaluated for the presence of adverse effects, degree of discomfort of the preparations (1: mild, 2: moderate, 3: severe) and the degree of cleansing with the products (1: poor, 2: fair, 3: good, 4: excellent). RESULTS: Age, sex, depth of insertion and surgical history were similar for both groups. Discomfort in the FS group was mild in 37, moderate in 11 and severe in 2 (mean score 1.30 +/- 0.54); in the PEG group it was mild in 28, moderate in 15 and severe in 7 (mean score 1.58 +/- 0.73). Colon cleansing was poor or fair in 11 (22%) patients in the PEG group and in 8 (16%) patients in the FS group and was good or excellent in 39 (78%) in the PEG group in comparison with 42 (84%) in the FS group. Among the 50 patients who took the FS preparation, 12 had previously taken the PEG preparation and 11 of these preferred the FS preparation. Among the 50 patients who took the PEG preparation, 10 had previously taken preparations: 4 had used enemas (considering the present PEG to be worse) and 6 had taken the same PEG as that used in the present study (p < 0.005). One patient in the FS group and four in the PEG group did not complete the preparation because of vomiting. The adverse effects of both preparations were similar. CONCLUSIONS: The adverse effects and degree of colon cleansing were similar for FS and PEG. Tolerance and patient comfort were greater with FS than with PEG. PMID- 11219144 TI - [Therapy of HIV infection: how early and how intensive?]. AB - Three men aged 53, 25 and 34 years and 2 women aged 39 and 34 years with HIV infection had different courses with and without highly active antiretroviral therapy (HAART). Medication regimes were often complicated and adverse events occurred frequently, which led to adjustment of treatment. Since the introduction of HAART for treatment of HIV infection, a tremendous progress has been achieved, resulting in reduction of HIV related events and in reduction of fatality due to AIDS. However, besides the positive effects of this therapy, there is also a negative side of HAART. In addition to the complexity and adverse events, the medication has to be taken lifelong while non-compliance might result in resistance-mutation. If HAART might be indicated, it is necessary to weigh the pros and contras before starting with medication. PMID- 11219146 TI - [Physical diagnosis--pain elicited by percussion in the kidney area]. AB - Percussion of the kidney as a diagnostic method was first described by John Benjamin Murphy (1857-1916). The test is rapidly elicited, but can cause severe pain. Considering acute pyelonephritis or acute renal colic, it is common practice to perform fist percussion of the kidney, yet its diagnostic value is unknown. Finnish study results in 1998 suggest that in acute renal colic loin tenderness and erythrocyturia are more significant signs than renal tenderness. There is no scientific evidence for determining renal tenderness in diagnosing urinary tract infections and urolithiasis. PMID- 11219145 TI - [Effect of aldosterone antagonism in heart failure: pharmacotherapeutic options]. AB - Aldosterone escape during chronic angiotensin-converting enzyme (ACE) inhibition may contribute to the high mortality among patients with heart failure. Aldosterone exerts several detrimental effects in the pathophysiology of heart failure. Spironolactone, an aldosterone antagonist, has proved beneficial when added to ACE inhibitors in patients with severe heart failure. However, spironolactone has substantial side effects mostly due to anti-androgen and anti progestagen actions. This may limit its use in less severe heart failure. Recently, more selective aldosterone antagonists have been developed, which appear to have the same potential as spironolactone with fewer side effects. Trials to assess efficacy of these drugs in hypertension and mild heart failure are now being started. PMID- 11219148 TI - [Diagnostic image (23). Congenital lobar emphysema]. AB - A 6-months-old-boy failed to thrive. Congenital emphysema of the left upper lobe of the lung was diagnosed, and lobectomy was performed, with good results. PMID- 11219147 TI - [CBO-guideline 'Bacterial meningitis']. AB - Neisseria meningitidis and Streptococcus pneumoniae are the most frequent causes of bacterial meningitis. The incidence of Haemophilus meningitis in the Netherlands is low due to successful Haemophilus influenzae type b vaccination. This implies that there is no need to take account into this microorganism in using initial empiric antimicrobial therapy for bacterial meningitis. Vomiting (especially children), headache, fever, and a stiff neck characterize acute bacterial meningitis. However, even without these signs a patient may still have acute bacterial meningitis. The characteristics in neonates are less specific. An emergency lumbar puncture should be performed in all patients with meningeal irritation or other signs of bacterial meningitis. Examination of the CSF is not indicated for convulsive children (between the ages of 6 months and 6 years) who do not exhibit other clinical signs. In patients who respond adequately to the treatment, it is not necessary to examine the CSF again. Papilloedema or focal neurological symptoms contraindicate a lumbar puncture in patients with bacterial meningitis, until CT results justify that it can be performed safely. Antibiotic treatment should not be delayed until after the CT. General practitioners should treat their patients with suspected meningococcus infection by admitting them to the hospital without first injecting antibiotics. In the Netherlands, patients with suspected pneumococcus meningitis may still be treated with benzylpenicillin. Patients with bacterial meningitis have no fluid restrictions; only in case of the syndrome of inadequate secretion of antidiuretic hormone is fluid reduction indicated. The physician is responsible for prescribing prophylaxis to family members. The Regional Health Services organize chemoprophylaxis for classmates. The latter is only indicated if at least 2 related cases occur in one month. PMID- 11219149 TI - [Teaching to inhale: better utilization of powder inhalators after counseling and instruction]. AB - OBJECTIVE: To study the effect of instruction of patients who used an dry powder device on the correct performance of the inhalation technique and whether the effect lasts. DESIGN: Prospective. METHOD: A number of patients who used at least one drug by the dry powder devices Diskhaler or Diskus/Accuhaler were asked to demonstrate their inhalation technique in the outpatient clinic, Department of Pulmonary Medicine, Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands. On a score list the receptionist recorded the correctness of every step of use of the device. Then information and instruction on the correct performance of the inhalation technique were supplied by the same receptionist until the patient mastered the inhalation technique. A simple instruction card was handed to the patient. At the next outpatient visit the effect of the instruction was measured by means of the same score list registered by the same or another receptionist. RESULTS: Data from 97 patients could be evaluated; 42 men and 55 women, with a mean age of 58 years (range: 16-84). The percentage of patients who performed all essential actions correctly increased from 12 to 62. Almost all actions were performed better at the second than at the first visit. Better inhaling technique was observed in the 53 patients who paid their second visit within 30 days as well as in the 44 who came later (mean: 96 days; range: 34-352). CONCLUSION: The performance of the inhalation technique with the Diskhaler and the Diskus/Accuhaler was poor. By means of instruction the inhalation technique improved. This improvement was also seen in the group checked after an average of 3 months. PMID- 11219150 TI - [Acute schistosomiasis: fever and eosinophilia, with or without urticaria, after a trip to Africa]. AB - Despite treatment for malaria two travellers who acquired fever in Africa continued to have complaints: a 25-year-old Dutch woman and a 25-year-old Australian man. On questioning they appeared to have swum in Lake Malawi and a diagnosis of acute schistosomiasis was made, confirmed by serological tests. This syndrome, also called Katayama fever, is characterized by fever, oedema, urticaria and eosinophilia. The aetiology is not fully elucidated but it is supposed to be caused by immune complexes initiated by maturing worms and eggs. Patients who acquired fever in an endemic area must be questioned about contact with fresh water. Serological tests are important for the diagnosis. Treatment is with praziquantel but it is advised to treat only after the acute phase. During the acute manifestations corticosteroids may be necessary. Prevention is by avoiding contact with infected water. There is no vaccine. The role of artemisinin drugs in prevention is currently being studied. PMID- 11219151 TI - [Acute delirium, probably precipitated by clarithromycin]. AB - Clarithromycin is a relatively new antibiotic with many applications. Its frequent use explains why side-effects previously reported seldom now become clear. Two patients, a man aged 74 and a woman aged 56 years, developed delirium after treatment with clarithromycin as part of eradication treatment of Helicobacter pylori, presumably as a result of an ideosyncratic reaction to the clarithromycin. Preclinical and clinical investigations did not reveal side effects on the central nervous system. By now the appearance of a delirium presumably related to the use of clarithromycin has been described in several patients. Furthermore some patients had a positive rechallenge. Finally, 17 reports on psychiatric side effects, of which 7 were delirium, after the use of clarithromycin reached the Netherlands Pharmacovigilance Foundation (Lareb). This combination of facts makes a causal relationship probable. PMID- 11219152 TI - [Ethical shortcomings of skeletal age determination to establish minority for single young asylum seekers]. AB - Each year tens of thousands of asylum seekers from all over the world come to the Netherlands. Amongst them are minors who come alone. They are eligible for a separate, less severe, admittance procedure than for adults and their under-age children. Because of abuse of this procedure by adults an X-ray age examination of the claviculae and hand-wrist has been introduced to determine minority. A person who claims to be a minor but appears to be an adult is invited to submit to the examination on a 'voluntary' basis. The selection procedure, the informed consent, the voluntariness and the technical aspects of the age measurement suffer from ethical shortcomings. An ethical committee should ensure that the procedures conform to the generally accepted Dutch ethical principles laid down in the Dutch Medical Treatment Act. In addition, the selection of asylum seekers for age determination should be carried out by specialized officials (an alternative would be to subject all single minor asylum seekers to age measurement). The waiting time for age measurement should be reduced to prevent the medial clavicular epiphyseal disc from closing during the waiting time. Age should not be judged on the basis of a partially closed epiphyseal disc, as this is controversial. It is recommended that the age for the single minor asylum seeker regulation be reduced from 18 to 16 years. PMID- 11219153 TI - [Good medical care at the borderline of mental incompetence]. PMID- 11219154 TI - [Bizarre advertisements by hospitals in the Dutch Journal of Medicine]. PMID- 11219155 TI - [Cholesterol-lowering therapy; a recommendation from the Health Council]. PMID- 11219156 TI - [Fabry disease: data from 4 families]. PMID- 11219157 TI - [Link between prenatal exposure to the 'Winter of Famine' and long-term medical consequences]. PMID- 11219158 TI - [Acquired medical condition and driving ability]. PMID- 11219159 TI - [Primary osteomyelitis of sternum]. PMID- 11219160 TI - [Primary osteomyelitis of sternum]. PMID- 11219161 TI - Folate and intrauterine growth retardation. AB - The objectives of this case-control study were to compare the levels of folate in cord and maternal blood of 315 mothers who had intrauterine growth-retarded (IUGR) babies and 321 mothers who had appropriate-for-gestational-age (AGA) babies, to evaluate the correlation between cord and maternal folate and to assess the prevalence of folate deficiency. Mothers were recruited from the four largest hospitals in Campinas city, south-east Brazil. The gestational ages of the newborns were evaluated by the Capurro method. They were classified as being IUGR according to the Lubchenco birthweight-for-gestational-age standard. Red blood cell (RBC) folate was measured by radio-immunoassay. Slightly more IUGR (25.7%) than AGA babies (19.9%) had cord folate levels < or = 226.5 nmol/l (100 ng/ml) (p = 0.05) and similar percentages of IUGR (32.1%) and AGA (29.9%) mothers had folate levels < or = 226.5 nmol/l. Mean cord folate levels in IUGR and AGA babies were 10% higher than mean folate levels in the two groups of mothers (p < 0.001). There were weak correlations between maternal and cord folate in IUGR (r = 0.31) and AGA (r = 0.35) (p < 0.001) mother/baby groups. In this population, 35% of mothers were folate-deficient although it was not associated with IUGR. Nevertheless, it would be important to give Brazilian women folate tablets during pregnancy and to investigate the effect on concentrations of homocysteine and on the prevalence of birth defects. PMID- 11219162 TI - No strong long-term effect of vitamin A supplementation in infancy on CD4 and CD8 T-cell subsets. A community study from Guinea-Bissau, West Africa. AB - The World Health Organization recommends that 100,000 IU of vitamin A be given to infants between 6 and 12 months of age at the same time as measles vaccination in order to prevent vitamin A deficiency. In the present study, our aim was to assess the effect of vitamin A supplementation on T-cell subsets in a randomized factorial design, seeking a possible modifying effect of measles vaccination. Three hundred children were allocated either to two doses of measles vaccine at 6 and 9 months of age or to poliomyelitis vaccine at age 6 months and measles vaccine at age 9 months. Within each group, infants were to receive two doses of vitamin A or two doses of placebo at 6 and 9 months of age. We found no significant effect of vitamin A supplementation on CD4 and CD8 T-cell subsets at 3 and 9 months after supplementation. We found no effect of measles vaccine and no interaction between vitamin A supplementation and measles vaccine. Based on these observations, vitamin A supplementation does not seem to have a strong long term effect on CD4 and CD8 T-cell subsets in infants without clinical vitamin A deficiency. PMID- 11219163 TI - Independent indicators of outcome in severe paediatric malaria: maternal education, acidotic breathing and convulsions on admission. AB - Severe malaria is an important cause of death in hospitalized children in Mozambique, but the risk factors for this remain unclear. The objectives of the study were to define simple clinical criteria to identify on admission the children most at risk of dying. We studied prospectively 559 children admitted with severe malaria to the Department of Paediatrics of the Central Hospital of Maputo, Mozambique between March 1995 and August 1996. The case fatality rate was 3.6%. In a multiple logistic regression model, mothers' education (RR = 9.6, 95% CI 1.2-76.0), acidotic breathing (RR = 4.3, 95% CI 1.3-13.8) and convulsions in the emergency room (RR = 8.1, 95% CI 2.6-25.1) were associated with outcome. Together they predicted 97% of outcomes but only 33.3% of deaths. PMID- 11219164 TI - Comprehensive community effectiveness of health care. A study of malaria treatment in children and adults in rural Burkina Faso. AB - Malaria is one of the most important causes of morbidity and mortality in children in sub-Saharan Africa, yet community effectiveness of treatment is not well understood. This study presents a quantitative estimate of community effectiveness of malaria treatment in Burkina Faso, based on population surveys, observational studies of health services and user surveys. Analysis of seven steps in the process of treating malaria reveal the following: (1) 21% of people with malaria attend health centres; (2) 31% of them have a sufficient history taken; (3) 69% receive a complete clinical examination; (4) 81% receive the correct dosage of drugs prescribed; (5) 91% purchase the drugs; (6) 68% take the drugs as prescribed; (7) the drugs are estimated to be 85% effective. Taking all the steps into account, overall community effectiveness is estimated to be 3%. Statistically significant differences in age and gender are seen in some steps. Quinine is prescribed too frequently. Critical issues in educating health care workers include complete history-taking and clinical examination, rational indication for quinine and adjusted drug dosages for children. We identify utilization and diagnostic quality as offering the greatest potential for improvement in overall community effectiveness. PMID- 11219165 TI - Cystic fibrosis in Arabs: a prototype from Jordan. AB - Cystic fibrosis is believed to be rare in Arabs. We report 202 cases (114 boys and 88 girls) diagnosed in Jordan over a period of 9 years. The mean age at diagnosis was 2.9 years. Classical presentation with growth failure, malabsorption and respiratory symptoms occurred in 75.4% of cases. Eighteen (10.8%) presented with hepatomegaly, 12 (7.2%) with meconium ileus and 11 (6.6%) had Pseudo-Bartter syndrome. Thirty-eight (23%) children died, most below the age of 1 year which may reflect a more severe disease in our population. Consanguineous marriage was present in 69% of cases. Genetic screening of 84 children and 66 parents revealed 24 different CFTR mutations with a DF508 mutation accounting for only 7.4%. Among the mutations detected, six were alleles identified for the first time. The fact that boys outnumber girls might reflect more deaths in girls due to the observed gender gap in CF mortality. It is possible that the low incidence of the DF508 mutation is due to a confounding effect and the high mortality in those carrying this mutation. The large number of different mutations reflects the ethnic diversity of the Jordanian population and the complex history of the country. PMID- 11219166 TI - Prognostic aspects of cystic fibrosis in Brazil. AB - Selected prognostic factors were assessed in a cohort of 111 Brazilian children with cystic fibrosis diagnosed between 1 June 1970 and 31 December 1994 and followed in the Pediatric Pulmonology Unit of the Federal University of Minas Gerais Hospital. A standardized protocol was used to collect information retrospectively from medical charts which included date of birth, age at diagnosis, gender, ethnic group, predominant mode of presentation, duration of follow-up, status on 31 December 1994, date of death or date of the last clinical evaluation. The risk of death (univariate and multivariate) was assessed using Cox's proportional hazard model. Mean age at death was higher in males (5.10 years), when the diagnosis was made before the age of 12 months (3.10 years), when clinical presentation was other than respiratory (4.01 years old) and in 'non-whites' (4.86 years old). Age at diagnosis was the only factor associated with death in this population, with both Cox's univariate (RH: 19.4) and multivariate analyses (RH: 17.6; 95% CI: 4.8-64.1). The increased risk of dying in children diagnosed before 12 months of age found in our analysis indicates that they should receive differentiated and intensive multi-professional care. PMID- 11219167 TI - Cerebrospinal trypanosomiasis masquerading as pulmonary infectious disease in a 1 year-old boy. AB - A 1-year-old boy with cerebrospinal trypanosomiasis presented with severe respiratory symptoms, hepatosplenomegaly and no neurological signs of trypanosomiasis. Agitation and high fever on the 2nd day in hospital prompted a lumbar puncture and trypanosomes were recovered from the cerebrospinal fluid. PMID- 11219168 TI - Typhoid fever, ciprofloxacin and growth in young children. AB - Typhoid fever remains a significant public health problem in Southern Asia, particularly with the emergence of multi-resistant strains of Salmonella typhi in the late 1980s. Use of ciprofloxacin in children, although discouraged, is increasing and we aimed to assess whether its use affects growth or the prevalence of joint symptomology. Children under 6 years of age diagnosed as typhoid fever on the basis of a positive Widal test were recruited in the outpatient department of a paediatric teaching hospital after treatment had been initiated. During 6 months follow-up, prevalences of arthritis/arthralgia and ponderal, linear and knemometric growth were recorded. Seventy-five children were recruited (mean age 32 months, mean weight-for-height Z-score--1.3, mean height for-age Z-score 1.4) and 29 (39%) of them received ciprofloxacin. No significant adverse effects on ponderal, linear or knemometric growth, or on the incidence of arthritis/arthralgia were found to be associated with the use of ciprofloxacin. Knemometric and ponderal catch-up growth was demonstrable 30 days after diagnosis but linear growth was still declining 3 months after diagnosis with catch-up growth demonstrable only after 6 months. We conclude that ciprofloxacin is commonly used in typhoid fever and has no adverse effects on growth or joint symptomology. PMID- 11219169 TI - Childhood immunization in rural Malawi: time of administration and predictors of non-compliance. AB - A cohort of 760 newborns was followed prospectively for 2 years to ascertain the time of administration of childhood vaccinations in rural Malawi and to study predictors of non-compliance with national vaccination recommendations. At 1 year of age, 99% of the infants were fully vaccinated against tuberculosis, 91% against polio, 90% against diphtheria, pertussis and tetanus and 64% against measles. At 2 years, the corresponding vaccination coverages were 99%, 93%, 93% and 84%. On average, all vaccinations were given 1-3 months later than recommended. Many of the delayed measles vaccinations were given during a separate vertical campaign, during which 25% of previously unvaccinated 21-23 month-old children were identified and immunized. Non-compliance with vaccination recommendations was associated with living in villages with no access to mobile vaccination teams, birth between April and June and birth at home. In this rural Malawian area, most vaccination services were functioning well. To increase measles vaccination coverage, regular outreach activities should be encouraged. PMID- 11219170 TI - Levels and avidity of antibodies to tetanus toxoid in children aged 1-15 years in Dar es Salaam and Bagamoyo, Tanzania. AB - A study was undertaken to determine the serological response in children (aged 1 15 years) immunized with diphtheria-pertussis-tetanus vaccine (DPT) alone or with a tetanus toxoid (TT) booster dose under the Expanded Programme on Immunization in Dar es Salaam and Bagamoyo, Tanzania. Using an ELISA technique, serum levels of anti-TT antibody, antibody avidity and anti-TT IgG subclasses were determined in 138 apparently healthy children. Our findings revealed that 94.7% and 98% of children aged 1-5 years in Dar es Salaam and Bagamoyo, respectively, had anti-TT antibody levels above that considered protective (> or = 0.1 IU/ml). Among 6-15 year-old children, 53.3% in Dar es Salaam and 55% in Bagamoyo had anti-TT antibody levels > or = 0.1 IU/ml. The avidity index of anti-TT antibodies was high in most of the younger children, 84.2% in Dar es Salaam and 92% in Bagamoyo. Significantly fewer older children in Dar es Salaam and Bagamoyo (53.3% and 50%, respectively) had high avidity index antibodies. The predominant anti-TT IgG subclasses were IgG1 and IgG3. It is concluded that the current DPT immunization schedule provides adequate tetanus immunity for children under 5. However, about half of the older children had no protection against tetanus. PMID- 11219171 TI - Neonatal neurological testing in resource-poor settings. AB - The aim of the study was to design and test a neurological examination for newborns that could be performed reliably by paramedical staff in resource-poor settings. The examination was adapted from a method established by Dubowitz et al., the latest version of which includes an optimality score. The final items in the test were chosen because they were culturally acceptable, could be elicited according to strict but easily comprehensible instructions and because the expected responses could be scored by the descriptions given or by diagrams in the proforma. The shortened examination was easily taught to paramedical staff who achieved a high degree of inter-observer reliability. This shortened version of the examination was piloted by comparing newborns from a Karen refugee camp on the western border of Thailand and from a large maternity hospital in Bangkok with a standardized cohort of newborns in London. The modified shortened version of the test was sufficiently sensitive to identify a number of differences between the cohorts, notably the poor vision performance and markedly reduced tone of the Karen newborns. In conclusion, the test can be used very reliably by paramedical staff and is a useful, simple and portable tool for the neurological assessment of newborn babies where resources are limited. PMID- 11219173 TI - Short stays in hospice. A review & update. AB - Despite the proven benefits and popularity of hospice, the average hospice patient receives only one month of services before death. Advanced progression of a patient's disease at admission contributes to short lengths of stay, and precludes patients from receiving the full benefit of hospice services. This article uses the results of the literature review to articulate reasons for delayed enrollment and to advance suggestions for ameliorating the problem of short stay in hospice. PMID- 11219172 TI - Incidence and spectrum of congenital heart disease in Oman. AB - We analysed the incidence and spectrum of congenital heart disease (CHD) in the Sultanate of Oman from 1994 to 1996. CHD was detected in 992 of 139,707 live births (incidence 7.1/1000 live births). The common CHDs were ventricular septal defect (24.9%), atrial septal defect (14.4%) and patent ductus arteriosus (10.3%). The frequency of atrioventricular septal defects (5.9%) was higher than reported from other countries. Age at diagnosis was under 1 month in 38% and 1-12 months in 40%. Cyanotic CHD was found in 21.7% of the whole group and 35% of neonates. Although this was a hospital-based study, we believe we included almost all the infants and children with CHD in the country. The incidence and pattern of CHD in Oman were similar to those reported from developed countries in Europe and America, except for a higher frequency of atrioventricular septal defects. The high prevalence of consanguinity in the country did not affect the overall incidence of CHD. PMID- 11219174 TI - Talbot Hospice Foundation. A successful community endeavor. AB - Since it opened its doors 20 years ago, the Talbot Hospice Foundation, located in Talbot County, Maryland, has grown to be one of the most highly respected service organizations in the county. A professional, non-medical staff of about five full time employees manages some 800 volunteers who offer free hospice services to anyone in the community. It is dedicated to the concept that dying is not just a medical event, and that trained community lay people can play a significant role in providing practical and emotional support to their neighbors. The Foundation is supported completely by donations and receives no reimbursement from Medicare or other insurers. PMID- 11219175 TI - Completing the continuum of care. The growth of a pediatric hospice program. AB - This article examines the process of integrating a pediatric program into an existing hospice organization. It also discusses the five phases a child and family experience, from entering hospice through grieving the loss of the child. PMID- 11219176 TI - Intimacy and the telephone. AB - While the opportunities for touch are absent, the opportunities for intimacy with an individual patient and caregiver are not, thanks to Hospice of Northern Virginia's telephone triage department. Achieving this intimacy across telephone lines is not happenstance; rather, it is a careful blending of home care and triage practice. The result is continuity of care and successful patient/family interactions. PMID- 11219177 TI - Volunteer Hospice Network. A grass-roots model for community coalitions. AB - In 1995, the Hospice Association of America established the Volunteer Hospice Network to promote the growth, diversity, and development of volunteer organizations that serve those who are dealing with life-threatening illness and those who are grieving. Partnerships between these volunteer hospices and Medicare-certified hospices may possibly be a part of the answer to the future of the hospice movement. PMID- 11219179 TI - The challenges & rewards of a hospice volunteer program. AB - This overview of a hospice volunteer program discusses the many aspects of running such a program, including finding volunteers, providing training and education, keeping volunteers motivated, and offering bereavement education. PMID- 11219178 TI - Love matters. A profile of Connecticut Hospice. AB - After 25 years, America's first hospice looks back at its past challenges and successes, and looks forward to continuing its mission into the 21st century. PMID- 11219180 TI - Preparing for the new hospice cost report. AB - All certified hospice providers are required to file cost reports for all cost report periods beginning on or after April 1, 1999. In addition, if the hospice cost report is filed late and/or is incomplete, Hospice Medicare payments will be withheld from the provider. Thus, it is imperative that agencies understand how to prepare for and complete the report properly. PMID- 11219181 TI - Honoring America's heroes. PMID- 11219182 TI - End-of-life issues. AB - In the Western world we have not fully accepted the fact that dying is indeed part of the process of living. Even today in the 21st century, physicians who have historically been taught to diagnose and treat disease with the expectation of cure, still regard death as a failure. We need to be reminded of the 15th century definition of medical care, "To cure sometimes, to relieve often, to comfort always." We must realise that we cannot defy death and that every individual on earth has no choice but to travel the journey, be it long or short, from birth to ultimate death. PMID- 11219183 TI - [Capacity limitation and intellectual ability]. AB - In a study examining the influence of cognitive capacity limitation on intellectual ability, 124 university students were subjected to 7 computer-based tests in which cognitive demands were manipulated by varying the number of required ordering, arithmetic, and memory operations, respectively. Intelligence data were obtained by forming a composite score from Raven's Advanced Progressive Matrices and the Berlin Intelligence Structure Test. Increases in cognitive demands led to increases in reaction times and number of errors as well as to increases in common variance and in correlations between intelligence and number of errors in 5 and 2 (of 5) comparisons, respectively, while correlations between intelligence and reaction time were found to decrease with increasing task demands in 3 comparisons. All correlations were reduced considerably when storage capacity and coordination efficiency were partialled out. These findings suggest a relationship between capacity limitation and intellectual ability. PMID- 11219184 TI - [Object-related action: use of recall in anticipation and performance]. AB - Consideration of the course of everyday actions during which real objects are manipulated would suggest that the sequence of individual activities should be represented in the memory not as a chain but as a network with specific characteristics. These characteristics would appear to indicate that activities which directly change parts of the environment are more memorable than shifts of attention during the performance of the action. The results of Experiment 1 support this view. Furthermore, it may be supposed that complex actions are not anticipated in their entirety before being performed, but only partially. Hypotheses concerning the temporal order of the parts of the anticipation process were tested in Experiment 2, the results supporting the hypotheses. Altogether, the results obtained confirm certain basic assumptions relating to the memory model Net of Recallable Action. PMID- 11219185 TI - [Structure and intensity of surprise]. AB - Two experiments investigated the multicomponent theory of emotion intensity proposed by Frijda, Ortony, Sonnemans, and Clore (1992) in the case of surprise and compared it with the more traditional "feeling element" approach to emotion intensity. In both experiments the participants performed a choice reaction time task for a certain number of trials. In the last trial they were surprised by an unexpected change of appearance of the stimuli. In Experiment 1 the change concerned either an action-relevant or an action-irrelevant, affectively neutral stimulus. In Experiment 2 the change concerned either an affectively positive or an affectively negative stimulus. Response delay in the surprise trial served as the index of the interruption of ongoing processes caused by surprise. Immediately after the surprise trial the participants completed a surprise intensity questionnaire that was an adaptation of the general emotion intensity questionnaire used by Sonnemans and Frijda (1994). In contrast to the findings of Sonnemans and Frijda (1994), the present findings were consistently better in line with the traditional feeling element approach to emotion intensity than with the multicomponent theory. Possible reasons for the failure to support the multicomponent theory of emotion intensity for the case of surprise are considered. PMID- 11219186 TI - [Effect of personal priorities on magnitude of stimulus preference: initial empirical findings]. AB - This study examines whether setting priorities in personal life-investment is reflected in a heightened sensitivity towards thematically related stimuli. Two groups of adults (N = 47; M = 30 years; 53% female) were compared: (1) participants with a parallel goal structure (n = 12) who feel equally committed to the work and the family domain, both in the present and in the future, and (b) participants with a sequential goal structure (n = 24), who currently feel more involved in the work domain, but expect to be more engaged in the family domain in the future. Five tasks were used to assess preference, all of them simultaneously presenting work- and family-related stimuli. As hypothesized, individuals with a sequential goal structure showed a stronger preference for work-related stimuli than individuals with a parallel structure. There were clear differences in word detection, in the elaboration of work-related statements, and in the choice between work-related and family-related reading material. Results are discussed primarily in reference to models of action-regulation. PMID- 11219188 TI - Role of blood coagulation factor XIII in vascular diseases. PMID- 11219187 TI - Evaluation of certain veterinary drug residues in food. AB - This report presents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs and to recommend maximum levels for such residues. The first part of the report considers an approach to assessing the safety of antimicrobial drug residues and their effects on the human intestinal microflora and general issues relating to the recommendation of Maximum Residue Levels (MRLs) for veterinary drug residues in food. A summary follows of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: one beta-adrenoceptor-blocking agent (carazolol), one anthelminthic agent (doramectin), four antimicrobial agents (dihydrostreptomycin, streptomycin, neomycin and thiamphenicol), two insecticides (deltamethrin and phoxim), four production aids (estradiol-17 beta, progesterone, testosterone and porcine somatotropins) and one tranquillizing agent (azaperone). Annexed to the report are a summary of the Committee's recommendations on these drugs, including Acceptable Daily Intakes and MRLs, and other information required. PMID- 11219189 TI - CD14 expression on monocytes and TNF alpha production in patients with septic shock, cardiogenic shock or bacterial pneumonia. AB - OBJECTIVES: In patients with septic shock, circulating monocytes become refractory to stimulation with microbial products. Whether this hyporesponsive state is induced by infection or is related to shock is unknown. To address this question, we measured TNF alpha production by monocytes or by whole blood obtained from healthy volunteers (controls), from patients with septic shock, from patients with severe infection (bacterial pneumonia) without shock, and from patients with cardiogenic shock without infection. MEASUREMENTS: The numbers of circulating monocytes, of CD14+ monocytes, and the expression of monocyte CD14 and the LPS receptor, were assessed by flow cytometry. Monocytes or whole blood were stimulated with lipopolysaccharide endotoxin (LPS), heat-killed Escherichia coli or Staphylococcus aureus, and TNF alpha production was measured by bioassay. RESULTS: The number of circulating monocytes, of CD14+ monocytes, and the monocyte CD14 expression were significantly lower in patients with septic shock than in controls, in patients with bacterial pneumonia or in those with cardiogenic shock (p < 0.001). Monocytes or whole blood of patients with septic shock exhibited a profound deficiency of TNF alpha production in response to all stimuli (p < 0.05 compared to controls). Whole blood of patients with cardiogenic shock also exhibited this defect (p < 0.05 compared to controls), although to a lesser extent, despite normal monocyte counts and normal CD14 expression. CONCLUSIONS: Unlike patients with bacterial pneumonia, patients with septic or cardiogenic shock display profoundly defective TNF alpha production in response to a broad range of infectious stimuli. Thus, down-regulation of cytokine production appears to occur in patients with systemic, but not localised, albeit severe, infections and also in patients with non-infectious circulatory failure. Whilst depletion of monocytes and reduced monocyte CD14 expression are likely to be critical components of the hyporesponsiveness observed in patients with septic shock, other as yet unidentified factors are at work in this group and in patients with cardiogenic shock. PMID- 11219191 TI - Transposition of great arteries and single coronary artery: a new surgical technique for the arterial switch operation. AB - A single coronary artery can complicate the surgical technique of arterial switch operations, impairing early and late outcomes. We propose a new surgical approach, successfully applied in a 2.1 kg neonate, aimed at reducing the risk of early and late compression and/or distortion of the newly constructed coronary artery system. PMID- 11219190 TI - The HMG-CoA reductase inhibitor simvastatin inhibits IFN-gamma induced MHC class II expression in human vascular endothelial cells. AB - HMG-CoA reductase inhibitors, or statins, are lipid-lowering agents that have been shown to effectively decrease severe rejection periods and development of transplant coronary artery disease after heart transplantation. Precise regulation of major histocompatibility complex class II (MHC class II) gene expression plays a pivotal role in control of the immune response after transplantation. The aim of this study was to evaluate the potential role of HMG CoA reductase inhibitors in regulating the immune response. We have examined the effects of simvastatin on MHC class II expression in primary human endothelial cells. Using RNAse protection assay and flow cytometry, we observed that simvastatin dose-dependently reduced interferon-gamma (IFN-gamma) induced MHC class II expression (mRNA and protein). In contrast, simvastatin did not affect the expression of MHC class I, pointing to specific actions in the MHC class II signalling cascade. The transcriptional coactivator CIITA is the general regulator of both constitutive and inducible MHC class II expression. After stimulation with IFN-gamma, the CIITA gene is selectively activated via one (promotor IV) of its four promoters. Interestingly, mRNA levels of CIITA were decreased after treatment with simvastatin. In addition, using transient transfections of promoter-reporter constructs we observed that the activity of CIITA promoter IV was decreased by simvastatin. In conclusion, simvastatin selectively decreases IFN-gamma-induced MHC class II expression in human primary endothelial cells through actions on the CIITA promoter IV. Thus, the beneficial effects of statins reported after heart transplantation may result from this immunosuppressive action, suggesting possible therapeutic use for other immunological disorders as well. PMID- 11219192 TI - Increased plasma adrenomedullin in patients undergoing percutaneous transluminal coronary angioplasty. AB - OBJECTIVES: Adrenomedullin (ADM) production and secretion have been reported in endothelial cells. The present study was designed to assess whether coronary angiography (CA) and percutaneous transluminal coronary angioplasty (PTCA) affect plasma ADM levels. DESIGN AND METHODS: We measured plasma concentrations of ADM using a specific radioimmunoassay method in patients undergoing coronary angiography or PTCA before and after a 5-minute procedure. Patients were divided into three groups; group I: normal coronary angiography group (11 males, 10 females; mean age 55.90 +/- 11.03 yrs), group II: coronary artery disease (CAD), only coronary angiography performed (14 males, 8 females; mean age 60.95 +/- 9.80 yrs), group III: PTCA performed in patients with CAD (35 males, 11 females; mean age 55.89 +/- 10.41 yrs). RESULTS: The plasma ADM levels and left ventricular end diastolic pressures measured before the procedure were similar in the three groups (p > 0.05). Plasma ADM levels were 13.98 +/- 2.26, 15.59 +/- 6.70, 17.15 +/- 8.47 pg/ml respectively. ADM levels measured after CA showed no significant difference in group I (13.75 +/- 1.75 pg/ml) or group II (16.50 +/- 7.18 pg/ml) (p > 0.05). A marked elevation was observed in group III with ADM levels of 27.31 +/- 12.27 pg/ml after PTCA (p < 0.01). The ADM levels observed in group III after PTCA were significantly higher than those of group I and group II after coronary angiography (p < 0.001). CONCLUSION: The results of our study show an increase of ADM after PTCA but not after coronary angiography in patients with or without CAD. We think that the increase of ADM levels may be due to cardiac secretion from endothelial and smooth muscle cells following balloon injury. PMID- 11219193 TI - Severe envenoming by a Gaboon viper (Bitis gabonica). PMID- 11219194 TI - Retirement Confidence Survey 2000 including results from the RCS Minority Survey and the Small Employer Retirement Survey. AB - The year 2000 represents the 10th anniversary of the Retirement Confidence Survey (RCS), and the third year for the Minority RCS and Small Employer Retirement Survey (SERS). Key RCS findings over the past 10 years include: The fraction of workers saving for retirement has trended upward, and today 80 percent of households report that they have begun to save. The fraction of workers who have attempted to calculate how much they need to save for retirement has risen noticeably over the past several years. Today, 56 percent of households report that they have attempted the calculation. One-half of workers who have attempted such a calculation report that it has changed their behavior, such as saving more and/or changing where they invest their retirement savings. Workers who have done the calculation appear to be in better shape regarding their retirement finances. Worker confidence in the ability of Social Security to maintain benefit levels bottomed out in 1994 and 1995. Workers today are just as confident as they were in 1992, although the majority remain not confident in Social Security. Regarding overall retirement confidence, Hispanic-Americans tend to be the least confident among the surveyed minority groups that they will have enough money to live comfortably throughout their retirement years. Key SERS findings include: While cost and administrative issues do matter to small employers, they are not the primary reasons for low plan sponsorship rates. Employee-related reasons are most often cited as the most important factor for not offering a retirement plan. Business-related reasons, such as profitability, are also a main decision-driver. It is important to note what small employers without plans do not know about plan sponsorship. Small employers that do sponsor a retirement plan report that offering a plan has a positive impact on both their ability to attract and retain quality employees and the attitude and performance of their employees. The survey results indicate that many small company nonsponsors may not be aware of such potential business benefits from plan sponsorship. In addition, many nonsponsors are unaware of the plan options available to them, in particular the ones created specifically for small employers, such as SIMPLE and SEP retirement plans. Therefore, some small employers may be making a premature decision not to sponsor a plan based on incomplete information. PMID- 11219195 TI - [The epidemiological approach and the good of the single individual]. PMID- 11219196 TI - [The Assessor is grateful]. PMID- 11219198 TI - [Our criticism is constructive]. PMID- 11219199 TI - [The WTO and asbestos: commerce above all]. PMID- 11219200 TI - [How difficult it is to measure the quality of life]. PMID- 11219201 TI - [Survival from neoplastic diseases and planning for oncological care]. PMID- 11219203 TI - [Health status indicators: features of the economic approach]. AB - Quality of Life (QoL) instruments are often considered similar, since they all concern subjective health state valuations. Actually, among the set of QoL scales, it is possible to distinguish two approaches, different in terms of both goals and tools. The clinical approach elicits functional limitations as perceived by patients, the economic approach is aimed at solving allocation problems generated by scarsity of resources. The major goal of this article is to analyse the economic approach to health state subjective valuation. By using QoL questionnaires, economists attempt to set up quantitative indexes which can value any kind of health outcome. Thus the economic approach seems to be more ambitious than the clinical one. However, the results so far achieved are quite disappointing, especially if compared to those of the clinical approach. In particular, economic scales still suffer a general lack of validation, due to the scarcity of studies conducted on relevant samples. Accordingly, indexes now available seem to require substantial revision. In general, further significant efforts seem necessary to improve the methodology inside the field of HRQoL measures. Integrating the two approaches, as recently attempted, could be a sound strategy. PMID- 11219202 TI - [Identification and mortality of Italian emigrants returning to Italy after having worked in the crocidolite mines at Wittenoon Gorge, Western Australia]. AB - The crocidolite mine at Wittenoom Gorge, Western Australia, has been active from 1943 to 1966, and managed by Australian Blue Asbestos Ltd (ABA). Migrants constituted the large majority of workers. The list of workers is composed of 6,911 subjects (6,501 males). In it we identified 1,102 Italians (1,069 males) and completed the follow up for those previously lost, remained in Australia or returned to Italy. Up to 1997, 302 subjects (301 males) definitively resettled in Italy, almost always returning to their community of origin. The median length of work at Wittenoom for those resettled was 17.8 months. The resettled subjects are spread around Italy, and 112 subjects (37%) already died. We compared the mortality rates of those returned to Italy to the rates of the male Italian population. Migrants were subjected to a strong selection before departure and were the target of a surveillance program during work at Wittenoom: however, for those resettled, instead of a healthy migrant effect, we observed an overmortality, mainly due to deaths from penumoconiosis (10 deaths vs 0.38 expected), from respiratory tumours (3 deaths from pleural mesothelioma and 4 from primary peritoneal tumours; an excess of lung cancers, SMR 1.28, 95% CI 0.72 2.11, and an excess of undefined caused of deaths (SMR 6.29, 95% CI 2.52-12.96). The study suggests that asbestos-related diseases and deaths have been observed among those resettled to Italy. In order to increase the precision of the follow up of the Wittenoom cohort, a search outside Australia should be carried out in some European countries for workers whose vital status was unconfirmed. Survivors in Italy are suffering from asbestosis, jeopardizing their life, and are at risk of cancer, but few have received information, actions aimed at reducing the accumulated risk, or compensation. Italy had a multi-million number of migrants for work, and an important percentage of migrants is returned to Italy: the effects of occupational exposures to adverse agents should be expected, but this topic has received up to now little attention. PMID- 11219204 TI - The "De morbis artificum diatriba" editions since 1700 and their legacy. PMID- 11219206 TI - [What is your diagnosis? Relative hypergonadotrophic ovarian insufficiency after chemotherapy for Hodgkin disease]. PMID- 11219205 TI - [Bernardino Ramazzini. Ante litteram epidemiologist]. AB - Bernardino Ramazzini, born in Carpi in 1633 and deceased in Padua in 1714, is universally renowned father and founder of occupational health. This paper will present Bernardino Ramazzini under a different perspective, and will show that during his scientific career he continuously maintained the attitude of a modern epidemiologist. Reviewing all his scientific papers, and many papers commenting his activity, we present four major areas in which Ramazzini expressed in a direct and convincing way his epidemiologic culture: the epidemiologic constitutions and the work done mainly on physical subjects while he was in Modena; the general architecture of his most important book (De Morbis Artificum Diatriba); the first full description of an episode of environmental pollution which occurred in Finale Emilia in 1689 (in his book this episode is reported in the chapter describing the diseases of chemicals); the opening lectures of some academic years he gave while he was teaching, mainly, in Padua. To our knowledge the epidemiological attitude of Bernardino Ramazzini is not recognized yet in epidemiology textbooks. PMID- 11219207 TI - [General practice and home blood pressure measurement with fully automated device in long-term comparison]. AB - In this prospective cohort study on 43 patients, the blood pressure patterns measured fully automatically in the doctor's practice and at home were compared over an average period of eight months. In total, a highly significant correlation was found between professional and patient measurements for both systolic and diastolic values. However, over the entire study period, the values obtained in the doctor's practice were higher than the patient's measurements (systolic +17 mmHg, diastolic +9 mmHg). The values obtained in the practitioner's office exhibited a much greater fluctuation than the patient's measurements. The majority of the values measured in the practice were above the mean of the home measurements (65% systolic and 67% diastolic). On therapy, 28 percent of the patients showing hypertensive values in the practice measured normal pressures at home. In conclusion, the study shows a minor fluctuation and a better reproducibility of the patient's own measurements versus those taken in the practitioner's office. PMID- 11219208 TI - [Endoluminal, cardiovascular radiotherapy: a new standard]. AB - The treatment for cardiovascular disease, especially the treatment of coronary stenosis, has been continuously improving during the last decades. Routine use of angioplasty was improved by the use of coronary stenting further reducing cardiac morbidity. However, the incidence of restenosis after cardiovascular angioplasty remains high. The restenosis process is mainly explained by neointimal proliferation. Therefore, the utility of ionizing radiation has been systematically investigated in order to reduce proliferation of the neointimal tissue. Radiation therapy turns out to be a very efficient approach in reducing the rate of both de novo lesions as well as of instant restenosis. Recent clinical data from randomized trials confirm the utility of intracoronary radiation therapy and change the treatment standards in interventional cardiology. PMID- 11219209 TI - [Using diffusion and perfusion imaging of the brain with magnetic resonance tomography]. PMID- 11219210 TI - [Penile metastasis of carcinoma of the urinary bladder]. PMID- 11219211 TI - [Heracl'eum mantegazzi'anum: photosensitization]. PMID- 11219212 TI - [Multiple morbidity in a patient (87 years old)]. AB - The group of aged people--in particular of highly aged persons--increases and with it also the risk of polymorbidity. Atherosclerosis often occurs in the elderly population; it is not astonishing that atherosclerosis also increasingly affects the renal arteries. Another problem in this age group is chronic back- and leg pain. Considering a medicine that respects the patient's attitude and is reasonable and cost-effective, the care and therapy of a polymorbid patient offers a special challenge in the modern evidence-based medicine. PMID- 11219213 TI - Politics for dentists and dentistry--a grassroots view. AB - A Regent of the College who is involved in county government explains how he became involved in local politics and why participation at this level matters. PMID- 11219214 TI - Above all, check your references. PMID- 11219215 TI - Dentists serving their communities and states. AB - An orthodontist from Utah describes the motives and rewards for public service at the city and state level. Timing, a desire to give back to the community, and good advice all play a role. PMID- 11219216 TI - A commitment to community. AB - Retiring Republican Member of Congress for the 48th District of California, Dr. Ron Packard reflects on the qualities of success that are common in dentistry and politics and stresses the importance of community. PMID- 11219217 TI - From private practice to public policy. AB - A dentist describes her journey from private practice to legislative assistant. Beginning with work in the ADA's Government Relations Office and then through the American Dental Association's Congressional Fellowship, Dr. Skoulas has now taken a full-time position monitoring and developing legislation for Congressman Edward J. Markey. PMID- 11219218 TI - Reflection, introspection, and communication: a psychologist's view of dental ethics. AB - A psychologist with experience teaching ethics in dentistry observes that ethical practice involves three skills: reflection (to understand the ethical issue), introspection (to discover the forces for action), and communication (to carry ethics into action). Several short cases are presented showing how ethical communication can be difficult. Direct communication (what psychologist call confrontation) is recommended and some tips are offered. PMID- 11219220 TI - Will you accept this responsibility? PMID- 11219219 TI - Advertising, commercialism, and professionalism: a history of the ethics of advertising in dentistry. AB - The authors "read" the historical dental codes prohibiting advertising and the U. S. Supreme Court decision striking down prohibitions against advertising by lawyers in Arizona, and by extension, professional advertising generally. The arguments presented in defense of prohibiting professional advertising and the court's responses to each are presented in detail. The current ADA code is analyzed in this context. PMID- 11219221 TI - Having your say. AB - Effectiveness in speaking at meetings is more a matter of fit with the emerging image the group has of itself than the persuasiveness of the speaker. In addition to rhetorical messages, people speak at meetings to confirm their right to membership, obtain or exercise status, achieve social goals, and provide or reinforce the structural and procedural needs of the group. Persuasive speeches should fit the flow of the meeting, state the desired result of the speech, and give a reason. Style points are also mentioned. PMID- 11219222 TI - Stress-induced hormonal alterations. AB - The hormonal alterations observed during critical illness are extremely diverse, being both adaptive and maladaptive. Central and peripheral mechanisms are at play depending on the duration and severity of the insult. Perturbations in the endocrine axes are exacerbated by endogenous mediators and by pharmacologic intervention. The emergence of the concept of the wound, or inflammatory lesion, as an endocrine organ introduces new potential mechanisms of stress physiology and possible interventional strategies. Whether the physiology of the wound can be manipulated to heighten organism resistance to stress either emergently or electively is theoretically appealing and supported by animal models. Currently, however, it remains a subject of ongoing controversy and research. PMID- 11219223 TI - Stress-induced hyperglycemia. AB - Stress hyperglycemia is common and likely to be associated with at least some of the same complications as hyperglycemia in true diabetes mellitus, such as poor wound healing and a higher infection rate. The predominant cause is the intense counterregulatory hormone and cytokine responses of critical illness, often compounded by excessive dextrose administration, usually as TPN. Although randomized data suggesting benefit of controlling hyperglycemia in hospitalized patients are paltry, prospective controlled trials are feasible and should be initiated. In the interim, the practice at the authors' institution is to use insulin to lower plasma glucose concentrations to a safe range of 150 mg/dL to 200 mg/dL in all patients. PMID- 11219224 TI - Syndromes of excess antidiuretic hormone release. AB - Hyponatremia, particularly that due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH), is common in patients seen in the critical care setting. Because of aging-associated changes in the hormonal and renal systems involved in regulation of water and sodium balance, older persons are at higher risk than the young. The high prevalence of disease states and drug use in the elderly can affect water and sodium conservation and further contribute to the risk of hyponatremia in this population. The approach to management is dependent both on the severity of hyponatremia-related symptoms and the rapidity with which hyponatremia has developed. Careful monitoring of serum sodium during treatment is essential to produce prompt resolution of symptoms while avoiding the development of central pontine myelinolysis. Several therapeutic modalities are available for the longterm management of chronic hyponatremia. PMID- 11219225 TI - Cerebral salt wasting syndrome. AB - There is significant evidence to show that many patients with hyponatremia and intracranial disease who were previously diagnosed with SIADH actually have CSW. The critical difference between SIADH and CSW is that CSW involves renal salt loss leading to hyponatremia and volume loss, whereas SIADH is a euvolemic or hypervolemic condition. Attention to volume status in patients with hyponatremia is essential. The primary treatment for CSW is water and salt replacement. The mechanisms underlying CSW are not understood but may involve ANP or other natriuretic factors and direct neural influence on renal function. Future investigation is needed to better define the incidence of CSW in patients with intracranial disease, identify other disorders that can lead to CSW, and elucidate the mechanisms underlying this syndrome. PMID- 11219226 TI - Hypocalcemic syndromes. AB - Hypocalcemia is common in the ICU and is a marker of poor prognosis. The mechanisms behind the low calcium levels include extravasation, increased chelation, intracellular overload of calcium, and an altered parathyroid hormone (PTH) secretion. Hypocalcemia and an altered PTH secretion seem to be related to systemic inflammation, but it is not known today if this response is appropriate or not. Therefore, a general supplementation with calcium in these patients cannot be recommended at this stage. PMID- 11219227 TI - Hypomagnesemic disorders. AB - Adequate magnesium stores are vitally important for life. Critically ill patients will almost always have diminished levels of circulating magnesium, and this predisposes them to a variety of adverse effects, some life threatening. The causes of hypomagnesemia are many and varied, but in the critically ill, losses from the kidneys, often secondary to medications and from the gastrointestinal (GI) tract, predominate. The measurement of magnesium is not straightforward, although many clinicians are now switching to the use of ionized magnesium from ion selective electrodes. The use of supplemental magnesium in acute flares of asthma has some support in medical literature, especially for those patients with severe disease who fail traditional therapy. Magnesium holds the preeminent position in the treatment of pre-eclampsia and eclampsia in the minds of most obstetricians, who have decades of experience showing it to be both effective and safe. Magnesium is clearly useful for certain types of ventricular tachycardia, and probably assists in the treatment of several types of supraventricular tachycardia. Its role in acute myocardial ischemia is less certain, although there is no benefit once reperfusion therapy has already been carried out. Finally, the role of magnesium in the treatment of acute cerebral insults is an exciting area of active investigation with initial studies suggesting much promise. PMID- 11219228 TI - Cardiovascular actions of magnesium. AB - Intracellular magnesium is an important modulator of calcium and potassium channels in cardiac myocytes. Hypomagnesemia is common in hospitalized patients and may contribute significantly to cardiac morbidity and mortality, particularly in states associated with myocardial ischemia. Therefore, it is important to maintain the plasma magnesium concentration within the normal range in asymptomatic patients and in patients with cardiac disease as prophylaxis against the occurrence of significant arrhythmias. PMID- 11219229 TI - Management of the obese critically ill patient. AB - The management of the morbidly obese critically ill patient is a challenging and formidable task. A better understanding of the pathophysiologic changes that occur with obesity and the complications unique to this group of patients may improve their outcome. PMID- 11219230 TI - Lipid modulation and systemic inflammation. AB - N-6 and n-3 PUFAs from the diet are absorbed and reach the cell where they interact with fatty acid binding proteins within cell membranes and cytoplasm. They are processed in the endoplasmic reticulum (desaturation-elongation reactions, lipid synthesis, eicosanoid and epoxide production) and in peroxisomes (beta-oxidation, synthesis, oxidation products). They interact with receptors, ion channels, and nuclear elements; the result is modulation of gene expression. PUFA-induced alterations result in modulation of local and systemic inflammation and inflammatory disease activity. PMID- 11219231 TI - Cytopathic hypoxia. Mitochondrial dysfunction as mechanism contributing to organ dysfunction in sepsis. AB - Several lines of evidence support the notion that cellular energetics are deranged in sepsis, not on the basis of inadequate tissue perfusion, but rather on the basis of impaired mitochondrial respiration and/or coupling; that is, organ dysfunction in sepsis may occur on the basis of cytopathic hypoxia. If this concept is correct, then the therapeutic implications are enormous. Efforts to improve outcome in patients with sepsis by monitoring and manipulating cardiac output, systemic Do2, and regional blood flow are doomed to failure. Instead, the focus should be on developing pharmacologic strategies to restore normal mitochondrial function and cellular energetics. PMID- 11219232 TI - Oxidants and antioxidant therapy. AB - The nature of organ injury during critical illness would suggest that antioxidant therapy might be effective as prophylaxis and therapy. To date, the results of human trials with these agents have yielded somewhat disappointing results. Future trials using better-defined primary endpoints for outcome and newly developed agents and modes of administration may result in successes in this field. PMID- 11219233 TI - Hypothalamic-pituitary-adrenal insufficiency. AB - Adrenal insufficiency is a common and underdiagnosed disorder that develops in critically ill patients. Most forms are acquired and will resolve with treatment of the underlying disease. Hypotension that is refractory to fluids and requires vasopressors is the most common presentation of adrenal insufficiency in the ICU. It is important to make the diagnosis of adrenal insufficiency, because current data suggest that treatment with glucocorticoids improves outcome. Diagnosis usually can be made on the basis of a stress cortisol level. Occasionally, when the level of stress is uncertain, the low-dose corticotropin stimulation test will be required for definitive diagnosis. A therapeutic trial with hydrocortisone should be started in patients with suspected adrenal insufficiency pending results of diagnostic testing. PMID- 11219234 TI - Thyroid function in the intensive care unit setting. AB - In sum, there is no convincing evidence yet published supporting the utility of T4 or T3 administration in patients with nonthyroidal illness. The authors recognize that evidence accrued in one disease state may not be applicable to others and that, although these studies are difficult to perform, further large scale prospective studies need to be performed. The issue of T3 treatment will not be resolved satisfactorily until more definitive data are available. Until that time, there may be rare circumstances when a clinician may think it best to treat an individual patient with T4 or T3. For the majority of patients, however, there will be little indication for the administration of thyroid hormones until the potential benefits can be shown to outweigh the risks. PMID- 11219235 TI - Management of hypothyroidism and hyperthyroidism in the intensive care unit. AB - Thyroid storm and myxedema coma are uncommon problems in the ICU, but both usually present with typical findings, and when recognized early, are treatable. Thus, rapid recognition with early institution of therapy may be life saving. It is always important to search diligently to determine the underlying cause of the decompensation and to treat that aggressively. PMID- 11219236 TI - Management of decompensated diabetes. Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome. AB - DKA and HHS represent two extremes in the spectrum of decompensated diabetes mellitus. Their pathogenesis is related to absolute or relative deficiency in insulin levels and elevations in insulin counterregulatory hormones that lead to altered metabolism of carbohydrate, protein, and fat and varying degrees of osmotic diuresis and dehydration, ketosis, and acidosis. In DKA, insulin deficiency and ketoacidosis are the prominent features of the clinical presentation, and insulin therapy is the cornerstone of therapy. In HHS, hyperglycemia, osmotic diuresis, and dehydration are the prominent features, and fluid replacement is the cornerstone of therapy. As many as one-third of patients may have mixed features of both DKA and HHS. Because the three-pronged approach to therapy for either DKA or HHS consists of fluid administration, intravenous insulin infusion, and electrolyte replacement, mixed cases are managed using the same approach. The therapeutic regimen is tailored according to the prominent clinical features present. In adult patients with mixed features, fluids may be administered more rapidly than they would be in younger patients, or in patients with DKA alone, because the risk for fatal cerebral edema in adults is low and the consequences of undertreatment include vascular occlusion and increased mortality. In younger patients with mixed features, rapid correction of metabolic abnormalities and, consequently, of hyperosmolarity by administration of hypotonic fluids and insulin should be avoided to decrease the risk for precipitating cerebral edema. In addition, if ketoacidosis has been a prominent feature in a mixed case, the patient may have type 1 diabetes with no residual pancreatic islet beta cell secretion and may subsequently need ongoing, life-long insulin therapy after resolution of the acute episode of decompensated diabetes. ICU admission is indicated in the management of DKA, HHS, and mixed cases in the presence of cardiovascular instability, inability to protect the airway, obtundation, the presence of acute abdominal signs or symptoms suggestive of acute gastric dilatation, or if there is not adequate capacity on the floor unit to administer the intravenous insulin infusion and to provide the frequent and necessary monitoring that must accompany its use. PMID- 11219237 TI - Postcoital contraception. PMID- 11219238 TI - Vaginal ring hormone delivery systems in contraception and menopause. PMID- 11219240 TI - Adolescent contraception and the clinician: an emphasis on counseling and communication. PMID- 11219239 TI - Mechanisms of pregnancy loss in antiphospholipid syndrome. AB - Antiphospholipid antibodies are associated with intrauterine fetal growth retardation and fetal distress leading to premature birth or fetal death. These complications are caused by uteroplacental insufficiency that is the result of multiple placental thromboses, infarcts, and spiral artery vasculopathy, which are almost certainly provoked by the hypercoagulable state induced by aPL antibodies. Available data indicate that the thrombogenic function of aPL antibodies involves their general effect on platelets, endothelial cells, anticoagulant mechanisms, and fibrinolytic pathways, as well as their local effect on trophoblasts and villi cells, leading to reduction of annexin V (placental anticoagulant protein-I) production and inhibition of its anticoagulant function. PMID- 11219241 TI - New contraceptive options. AB - New contraceptive modalities that are being introduced into the US marketplace reflect many changes in the delivery of existing steroidal products. These products are available now not only as oral medications but also as transdermal, intravaginal, intrauterine, and implantable or injectable devices. Each of these has its own unique profile and enhances the ability of consumers to pick and choose the product that is most acceptable to them. However, development of new barrier contraceptives, particularly those that have the potential to reduce the heterosexual transmission of HIV or to reduce a bacterial infection such as Chlamydia or Neisseria gonorrhea, continues to be moving forward in clinical trials. These products can have a lower efficacy compared with the steroidal products but, because of their other benefits, may be of significant medical use. PMID- 11219242 TI - Obstetric implications of antiphospholipid antibodies: pregnancy loss and other complications. PMID- 11219243 TI - Management of antiphospholipid syndrome during pregnancy. PMID- 11219244 TI - Antiphospholipid antibodies and infertility. PMID- 11219245 TI - Management of thrombosis in women with antiphospholipid syndrome. AB - 1) Antiphospholipid antibody syndrome may be associated with unusual sites of thrombosis. 2) Laboratory evaluation involves testing for antiphospholipid antibodies: lupus anticoagulant and anticardiolipin antibodies. 3) Acute management of thrombosis involves immediate anticoagulation. Low-molecular-weight heparins are as safe and effective as unfractionated heparin in this setting. Arterial events may require emergent thrombolytic therapy. Monitoring of the APTT with unfractionated heparin in the presence of a lupus anticoagulant is ineffective; these patients require monitoring of antifactor Xa levels or the use of LMWH, which does not require monitoring. 4) The pharmacokinetics of LMWH change in pregnancy, resulting in a shorter plasma half-life and larger volume of distribution. Monitoring of antifactor Xa levels is necessary. 5) Chronic anticoagulation is best achieved with warfarin, with significantly decreased rates of recurrent events when the INR is > or = 3.0. Long-term, if not life long, anticoagulation is often necessary. Warfarin is teratogenic, and individuals desiring pregnancy will need to convert to therapeutic, not prophylactic, doses of either unfractionated heparin or LMWH. 6) As part of optimal management of thrombosis in APS, additional risk factors for thrombosis should be eliminated or reduced. These include comorbid illnesses such as hypertension and hyperlipidemia, as well as smoking. 7) Tamoxifen, raloxifene, oral contraceptives, and hormone replacement therapy are all associated with an increased risk of DVT in the general population. In APS patients receiving therapeutic anticoagulation, the addition of these drugs should not increase thrombosis risk. In APS patients not receiving anticoagulant therapy, these hormonal therapies may increase the thrombosis risk. PMID- 11219246 TI - Testing for antiphospholipid antibodies: problems and solutions. AB - The first aCL test was developed in 1983 and subsequently standardized. Although new and more specific tests have become available, the aCL ELISA and the LA tests are still the first choice to be used in diagnosis of APS. Newer tests such as the anti beta 2 GP1 ELISA and the APhL ELISA Kit (Louisville APL Diagnostics) use somewhat different antigens and likely provide a more specific (and possibly more reliable) diagnosis of APS while retaining good-to-excellent sensitivity. Other tests, such as ELISA for prothrombin antibodies and annexin V antibodies, are still undergoing development and will require standardization and extensive evaluation. We thank Dr Isabel Abreu and Dr Mittermeyer B. Santiago for performing some of the studies reported in this review. PMID- 11219247 TI - Oral contraceptives: current status. AB - During the past four decades, oral contraceptives have remained a safe and effective method of birth control. Reductions in the estrogen and progestin dosages have significantly decreased the incidence of cardiovascular complications. The association between oral contraceptives and breast cancer appears to be primarily because of detection bias or possibly a promotional effect. Despite the changes in formulation, the problems related to side effects have not been totally solved. Because compliance and successful use is strongly affected by side effects, improvement in this area is probably the biggest challenge faced by developers of oral contraceptives. It is also clear that there are a growing number of significant noncontraceptive benefits that accrue in oral contraceptive users. Unfortunately, many women do not know about these benefits. Thus, one of the issues that providers need to continue to address is how to provide better information about oral contraceptives and contraception in general to patients. PMID- 11219248 TI - Injectable long-acting contraceptives. PMID- 11219249 TI - Norplant and other implantable contraceptives. AB - Implantable contraception represents a safe, reversible form of long-term family planning with distinct advantages. It does not contain estrogen, thus avoiding many of it contraindications. Importantly, it is extremely effective, has high continuation rates, and is well tolerated. The main side effects of Norplant are irregular menstrual bleeding and the occasional difficult removal. Although recent high-profile litigation has severely diminished enthusiasm for Norplant, the FDA has reaffirmed its safety and efficacy. Norplant remains a viable family planning option for carefully selected women. New contraceptive implants may soon be available accentuating the advantages of Norplant while minimizing the disadvantages. PMID- 11219250 TI - What health consumers want from online resources. PMID- 11219251 TI - Prophetic ministry in a new century. Prophets--lest we forget--are often unpopular in their own communities. PMID- 11219252 TI - CHA's refugee initiative. PMID- 11219253 TI - Non-heart-beating organ donation. Designing an ethically acceptable protocol. PMID- 11219254 TI - Organ donation and prudential deliberation. The opinions of physicians, other caregivers, and the public at large should be taken into consideration. PMID- 11219255 TI - Catholic systems: two years later. Two authors revisit strategic planning issues raised in a 1998 Health Progress article. PMID- 11219256 TI - 21st century strategic thinking. Five insights for boards of trustees. PMID- 11219257 TI - "Living our Promises, Acting on Faith". Year two update of CHA's performance improvement project in health ministry. PMID- 11219258 TI - The hiring process. Quality staff selection generates positive business results. PMID- 11219259 TI - Cutting costs in surgery. Rationalizing the use of surgical instruments can help hospitals stay competitive. PMID- 11219260 TI - Community networks. Partnerships between Catholic charities and Catholic health care organizations. Behavioral Health Care, Richmond, VA. PMID- 11219261 TI - The contemplative approach in the workplace. PMID- 11219262 TI - New collaboration aids refugees. PMID- 11219264 TI - Beyond the gift shop: making hospital retailing profitable. PMID- 11219263 TI - Enhancing relationships with local employers. PMID- 11219265 TI - Hospitals need to watch the viability of firms supplying content to their Web sites. PMID- 11219266 TI - The era of knowledge in health care. PMID- 11219267 TI - Health plan CEO offers tips on what hospitals need to do to serve seniors effectively. PMID- 11219268 TI - Health systems need to rethink post-acute care strategies in aftermath of BBA, PPS. PMID- 11219269 TI - Sleep disorders create growing opportunities for hospitals. PMID- 11219270 TI - Changing dynamics of integrated health care reports on major changes over five years. PMID- 11219271 TI - HIPAA is new weapon and career opportunity. PMID- 11219272 TI - New York, Florida, lead nation in AIDS rates, North Dakota has lowest rates. PMID- 11219273 TI - [New breast cancer diagnosis. False positive findings should become less frequent (interview by Petra Eiden)]. PMID- 11219274 TI - [BSE-cattle in Germany. Must we soon also count on vCJK patients?]. PMID- 11219275 TI - [Primary prevention of coronary heart disease. Exercise for life)]. PMID- 11219276 TI - [Homocysteine--CRP--lipoprotein (a). When do you evaluate the "new" risk factors]. AB - Homocysteine, inflammatory markers (e.g. CRP), hemostatic factors (fibrinogen, PAI-1, factor VII and factor VIII) and lipoprotein (a) are independent risk factors for atherosclerotic disease. Although the association between these factors and atherosclerosis is clear, it is uncertain whether this signals a causal relationship, or whether the parameters simply represent markers of atherosclerosis. Currently, there are no reports on interventional studies demonstrating a benefit from correcting these risk factors. The determination of homocysteine, fibrinogen and lipoprotein should therefore be restricted to certain situations, such as atherosclerosis or a family history of the disease without classical risk factors, or uncertainty about the need for primary pharmacological prevention. An increase in these parameters should prompt the early use of lipid-lowering drugs or aspirin. In exceptional cases only (homocysteine), correction of the risk factors should be considered. PMID- 11219277 TI - [Primary prevention in atherosclerosis. Properly assessing the risk of your patient]. PMID- 11219279 TI - [Detecting fungi in the intestines. Sometimes it pays off!]. PMID- 11219280 TI - [Tinnitus. Ways out of the diagnostic jungle in the direction of targeted therapy]. PMID- 11219278 TI - [Preventing coronary heart disease by physical activity. How much exercise is necessary?]. AB - The value of general measures, in particular physical exercise, for the prevention of cardiac disease has been unequivocally demonstrated. Meta-analyses done to investigate the preventive character of exercise have shown that the coronary risk of physically active persons is lower by a factor of 2 to 3. This reduction in risk is independent of the presence of other risk factors, and is not due to the better health awareness of those who are physically active. However, the amount or intensity of such training actually required remains uncertain. A number of studies report a protective effect only for intensive physical effort, while others claim a risk reduction independent of training intensity. In the last resort, however, any form of exercise is better than none at all, when it comes to lowering the coronary risk. Not only endurance sports, but also other types of sport, such as tennis, or daily activities, can be recommended. PMID- 11219281 TI - [Detection of disseminated tumor cells after cancer surgery. Indication of recurrence?]. PMID- 11219282 TI - [Diagnostic quiz. Increasing dyspnea after bypass operation. Interstitial lung disease]. PMID- 11219284 TI - [Sequlae of "silent rationing". Substantial deficits in drug management]. PMID- 11219285 TI - [Comprehensive anti-adrenergic therapy. It can save the weak heart]. PMID- 11219283 TI - [Orange peel skin provides business in the billions. But what really helps your patients?]. PMID- 11219286 TI - [30-year-old diabetic patients mostly have type 2 diabetes. "Mature" diabetics are becoming increasingly younger]. PMID- 11219287 TI - [Anti-inflammatory asthma therapy. Effectiveness depends on compliance]. PMID- 11219288 TI - [SERM-therapy in postmenopause. Protection of bone and breast]. PMID- 11219289 TI - [Best method against cellulite. Liposuction and freezing! (interview by Waldtraud Paukstadt)]. PMID- 11219290 TI - [An innovative treatment reported on television. Gene therapy against arthrosis?]. PMID- 11219291 TI - [15. Pathological liver values--alcohol is not always the problem!]. PMID- 11219292 TI - Appropriate antibiotic use: reducing the emergence and dissemination of resistance. PMID- 11219293 TI - Risk stratification for patients with community-acquired pneumonia. AB - Community-acquired pneumonia (CAP) is a common medical illness with a prognosis that ranges from rapid complete recovery to severe medical complications and death. Approximately 4 million adults are diagnosed with CAP in the US each year; with more than 600,000 (15%) hospitalised. An estimated $4 billion is expended annually on patients with CAP, with inpatient therapy costing as much as 20 times that of outpatient antimicrobial therapy. Determining severity of illness and using this information to risk-stratify patients with CAP is important from several perspectives. Clinically, understanding prognosis can assist physicians in the initial site of treatment decision (home versus hospital) and can be used to communicate expected outcomes to patients. From a research perspective, risk stratification can be used to select appropriate patient subgroups for clinical trials and to provide severity-adjusted outcomes comparisons. From a policy perspective, severity-adjusted outcomes can be used as a proxy for quality of medical care. PMID- 11219294 TI - Community-acquired pneumonia. PMID- 11219295 TI - Outpatient management of infectious diseases. PMID- 11219297 TI - Changes in drug resistance of bacteria in China. PMID- 11219296 TI - International outpatient parenteral antimicrobial therapy. AB - On an international basis, outpatient parenteral antimicrobial therapy (OPAT) varies greatly. There are cultural as well as economic issues which make it different in every country. In general, the duration of hospital stay varies with the outpatient resources available and the economic base for them. In some countries, there may not be money available for any intravenous antibiotics, even in the hospital. In addition, there are great differences in outpatient intravenous therapy, with infusion clinics proliferating in China, yet these are scarce in the UK. There is also considerable variation in the use of intramuscular compared with intravenous therapies. In Italy, intramuscular ceftriaxone is used more often than intravenous therapy. While ceftriaxone use is high in the US, its use is surpassed on a per capita basis by Italy, and it is most interesting that the rate of antimicrobial resistance is lower in Italy than in most other European countries. Whether this relates to outpatient use, parenteral use or other unknown factors is unclear. Obviously, further studies are necessary. PMID- 11219298 TI - Bioterrorism. PMID- 11219300 TI - History and future of pneumonia. PMID- 11219299 TI - Are we ready for emerging strains of pandemic influenza? PMID- 11219301 TI - Staphylococcus aureus small colony variants: formation and clinical impact. AB - S. aureus small-colony variants are a naturally occurring subpopulation which grow slowly and produce small colonies on routine media. They also demonstrate a number of other characteristics that are atypical for S. aureus including reduced alpha-toxin production and delayed coagulase activity. The connection of S. aureus SCVs with persistent and relapsing infections has been defined over the past decade, especially in patients with chronic osteomyelitis and in cystic fibrosis patients as demonstrated by prospective studies. While the studies with clinical isolates of SCVs suggested a link between electron transport-defective strains and persistent infections, a defined hemB mutant with the SCV phenotype provided strong additional evidence for these connections. The hemB mutant was phagocytosed by cultured endothelial cells, but did not lyse these cells, because the mutant produced very little alpha-toxin. The intracellular location may shield the SCVs from host defenses and antibiotics, thus providing one explanation for the difficulty in clearing S. aureus SCVs from host tissues. PMID- 11219302 TI - Otitis media--10 days versus 5 days versus none. PMID- 11219303 TI - New and emerging pathogens. PMID- 11219304 TI - The changing epidemiology of food-borne disease. PMID- 11219305 TI - Glycopeptide-resistant Staphylococcus aureus. PMID- 11219306 TI - Changing epidemiology of HIV. PMID- 11219307 TI - New rickettsial pathogens. PMID- 11219308 TI - Update on vancomycin resistance. PMID- 11219309 TI - Update on cross-resistance of fluoroquinolones. PMID- 11219310 TI - Is there still a role for penicillins and cephalosporins in the treatment of bacterial infections? PMID- 11219311 TI - Identifying priority patients for coronary angiography. AB - We conducted an open observational study with blinded endpoint evaluation to validate the use of the Duke treadmill score in identifying patients likely to require coronary intervention. We studied 101 consecutive patients referred for coronary angiography from a cardiology clinic. All patients had a Bruce protocol exercise test. A 70% stenosis was regarded as significant. Patients were referred for percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG) surgery, if indicated. The Duke score was calculated as follows: exercise time (min) - (5 x ST segment deviation [mm]) - (4 x angina index [text]). Patients were classified into low, medium and high risk. The patients at high risk are more likely to have a significant stenosis (53/58 vs 30/43: p = 0.01 [OR 4.59 95% CI 1.34-16.6]) and require CABG or PTCA (47/58 vs 16/43: p < 0.001 [OR 7.21 95% CI 2.69-19.8]) than those at medium/low risk. Multiple logistic regression analysis, including ST segment depression, exercise time and symptoms shows that the score independently predicts a significant stenosis (p = 0.002) and the need for coronary intervention (p = 0.001). Introducing the score can help to identify those patients who need priority investigation. PMID- 11219312 TI - The Foley catheter in the management of epistaxis. AB - The Foley urinary catheter has been used in the management of epistaxis for many years, yet it has never been designed or licensed for this purpose. We performed a telephone questionnaire of senior house officers in 90 ENT departments in England and Wales. The aim was to determine how many departments used the Foley catheter for epistaxis management, whether licensed nasal balloon devices were available and if there had been any complications associated with their use. Eighty-three (92%) ENT departments in the study used the Foley catheter for epistaxis management and 44 (49%) departments had licensed balloon devices available. Only 22% of ENT senior house officers questioned were aware that the Foley catheter was not licensed for use in the nose. Most complications associated with the use of nasal balloon devices appear to be due to Foley catheters. PMID- 11219314 TI - Conservative management of low back pain. AB - Back pain is prevalent worldwide, but back pain disability has reached epidemic proportions in many industrialised societies. Few patients have serious medical pathology or direct neurological involvement requiring surgery. Although the causes remain unclear, physical stress and its consequences on discs, facet joints and supporting soft tissues at work or leisure are important, sometimes aggravated by adverse psychosocial factors. Modern management emphasises the role of self-care, beginning in primary care with the first episode. Without root compression, bed rest should not exceed 48 hours. Emphasis is on encouraging a rapid return to physical fitness and other activities, including employment, acknowledging that returning to a normal life may require working through pain. Medication facilitates this. No one should remain in pain beyond six weeks without being referred to a specialist service for a physical and psychosocial assessment by appropriately trained professionals and with consultant support for investigation, pain management and rehabilitation when needed. PMID- 11219313 TI - What influences outcome of stroke--pyrexia or dysphagia? AB - To investigate the significance of pyrexia and dysphagia as risk factors for mortality at 90 days in patients admitted with an acute stroke when controlled with other confounding factors, 202 stroke patients admitted to acute medical wards were prospectively studied for demographic and neurological details, stroke syndromes and pathology. A number of other factors were recorded within three days of admission, including pyrexia and dysphagia. Cox's proportional hazards model was used to identify the effect of 10 factors on mortality at 90 days; 59 (29%) patients had died by 90 days. Univariate analysis revealed pyrexia and dysphagia to be independently and significantly associated with indices of stroke severity and 90 day mortality (p < 0.001 for both). Cox's proportional hazards model, however, revealed that stroke mortality was associated with dysphagia (relative risk 2.6, 95% CI 1.2-5.4; p = 0.009), pre-existing diabetes mellitus (2.4, CI 1.2-4.5; p = 0.006), higher age > 75 years (1.8, CI 1.0-3.1), ischaemic heart disease (2.1, CI 1.1-4.2, p = 0.025), total anterior circulation syndromes (2.8, CI 1.5-5.2) and previous stroke (1.8, CI 1.0-3.2, p = 0.028). Pyrexia was not a significant factor (p = 0.50). Although both pyrexia and dysphagia are associated with higher mortality in acute stroke patients, dysphagia was a significant variable predicting death at 90 days when controlled for other factors known to influence stroke mortality. Pyrexia is not significant when other variables are considered. PMID- 11219315 TI - Lessons to be learned--the blame culture. PMID- 11219317 TI - How do we prioritize patients on the waiting list for coronary angiography? PMID- 11219316 TI - Considerations for drug therapy in hypertension. AB - Both the Joint National Committee and the British Hypertension Society recommend b-blockers and diuretics as first-line therapy in the treatment of uncomplicated hypertension. As a result, many clinicians will also prescribe these drugs in the treatment of patients with hypertension and coexistent disease (unless they are specifically contraindicated), even though they may not always be the most beneficial choice. This review aims to examine factors that should be taken into consideration when choosing appropriate antihypertensive therapy. Particular attention is given to treatment options in two special patient groups, the elderly and patients with co-morbid diabetes, as these groups have an increased risk of developing cardiovascular complications. In response to the increasing evidence base from large-scale trials, the article concludes that cardiovascular risk factors, coexisting disease, concomitant medication and age should all be taken into account when choosing antihypertensive therapy. PMID- 11219318 TI - Consensus for the pharmacological management of insomnia in the new millennium. AB - Insomnia, a common symptom throughout the world, is characterised by difficulty initiating or maintaining sleep or non-restorative sleep and is associated with significant morbidity. A comprehensive medical and sleep history and physical examination are necessary before treating patients with insomnia; the presence of co-morbidities, including medical and psychiatric disorders, or the possible use of substances that may contribute to sleeplessness should be thoroughly investigated. Non-pharmacological approaches include correction of sleep hygiene as well as behavioural treatments. Pharmacotherapy includes benzodiazepine receptor agonists, which are the drugs of choice for this disorder. They can be subdivided into classic benzodiazepines and non-benzodiazepines. Although many agents in these classes have been prescribed, potential shortcomings include residual sedation, rebound insomnia, and psychomotor and memory impairment. Novel pharmacological strategies that address limitations of the traditional treatment approach, combined with proven modes of behavioural therapy, offer the most successful results in the management of insomnia. These advances provide the opportunity to establish these current recommendations for the optimal management of insomnia. This report from the XXII Collegium Internationale Neuro Psychopharmacologicum Consensus Workshop outlines recommendations to serve as the foundation for developing a therapeutic plan for each patient. PMID- 11219319 TI - Verapamil SR and trandolapril combination therapy is safe and effective in hypertensive patients with metabolic disorders. AB - Verapamil SR (180 mg) plus trandolapril (2 mg) is a potent antihypertensive combination but the efficacy and safety of this treatment has not been studied fully in hypertensive patients with metabolic disorders. We enrolled 298 patients with mild to moderate hypertension who had at least one of the following disorders: diabetes mellitus, hypercholesterolaemia or mild renal failure. The sitting systolic pressure and diastolic blood pressures were significantly decreased after 12 weeks of treatment. Blood pressure was inadequately controlled in only 24 patients (8.8%). Progressive decreases in blood glucose, total cholesterol, low-density lipoprotein and triglyceride levels were observed during the study. There was no significant change in blood urea nitrogen, creatinine and transaminase levels (p > 0.05). There was a significant decrease in microalbuminuria levels. There was no significant change in glycosylated haemoglobin levels in diabetic patients. Verapamil SR plus trandolapril is an effective drug combination in the treatment of hypertension. It may be used safely in patients with diabetes mellitus, hyperlipidaemia and mild renal failure. PMID- 11219320 TI - The pharmacology underlying pharmacotherapy for tobacco dependence: a focus on bupropion. AB - Tobacco dependence remains the major preventable cause of early mortality and morbidity in the developed world. The primary reinforcer of the dependence is the nicotine present in tobacco smoke and, for many smokers, successful treatment depends upon breaking this dependence. Until recently, the only specific pharmacotherapy available for tobacco dependence was nicotine replacement therapy (NRT). Although this approach does significantly increase long-term cessation rates, it is by no means a panacea for the many smokers who require help to quit. Recently, a new drug, bupropion (Zyban), has been licensed as an additional pharmacological aid for smoking cessation. This commentary discusses the mechanisms that may account for its efficacy in this indication and considers the impact its introduction may have on the approach of healthcare systems to the treatment of tobacco dependence. PMID- 11219321 TI - Linezolid. AB - Multiple antibiotic resistance is increasing worldwide in Gram-positive bacteria, especially in hospitals. Problem organisms include multiply resistant strains of pneumococci, Staphylococcus aureus and enterococci; for many of these the glycopeptide vancomycin has become the treatment of last resort. This situation has been made worse by the emergence of vancomycin-resistant enterococci and vancomycin-intermediate S. aureus. Fortunately, several compounds active against resistant Gram-positive bacteria are in active development. One of these is linezolid, the first of the oxazolidinones, a new class of antibacterial. Linezolid is a synthetic agent which is active against all the clinically important Gram-positive bacteria, including multiply resistant strains. It has good pharmacokinetics, with equal bioavailability by both oral and intravenous routes and no need for dose adjustment in patients with renal impairment. The drug has a good safety profile and clinical trials have given excellent results in a variety of skin and soft tissue, respiratory and bloodstream infections. Linezolid is a promising drug, which, together with prudent antibiotic use and the prevention and control of hospital infection, will help in the battle against multiply antibiotic resistant Gram-positive bacteria. PMID- 11219322 TI - A case of voluminous diarrhoea with hypokalaemic acidosis. AB - We describe a patient presenting with voluminous diarrhoea, hypokalaemic acidosis and hypercalcaemia who was found to have a vasoactive intestinal polypeptide producing tumour. His diarrhoea was initially mild and intermittent requiring no medical attention. PMID- 11219323 TI - Acute spontaneous haematoma of the rectum. AB - Gastrointestinal haematomata occur usually in the small intestine and may be secondary to anticoagulation. Spontaneous intramural haematoma of the rectum is rare. We report such a case which presented as acute abdominal pain and which was treated by simple drainage. PMID- 11219324 TI - Glossal palpation of the eustachian tube cushion: an unusual cause of globus sensation. AB - Globus sensation, the sensation of a lump in the throat, is a common symptom which, in its chronic form, accounts for 4% of first-patient visits to ENT clinics. We describe a rare cause of globus sensation and stress the importance of thorough investigation to exclude any possible organic causes. PMID- 11219325 TI - Cardiogenic shock following a single therapeutic oral dose of verapamil. AB - Cardiogenic shock and apnoea appeared in a 78-year-old woman with a history of biventricular heart failure, following ingestion of a single 80 mg verapamil tablet. She was resuscitated with artificial ventilation, dobutamine, norepinephrine and calcium gluconate. Toxicological analysis revealed unexpectedly high plasma verapamil concentration, which was attributed to the patient's liver failure. In patients with advanced heart failure a single oral therapeutic dose of verapamil may have a severe toxic effect. PMID- 11219326 TI - Coeliac disease and chronic fatigue syndrome. PMID- 11219327 TI - Implications of hypnotic flexibility on patterns of clinical use. AB - Insomnia is common among the primary care patient population, 1.3 times more common in women than men, and the prevalence increases with age. Until recently, benzodiazepines (BZs) were the only first-line hypnotics, but with the availability of non-BZ sleep agents, the management of insomnia is changing. Zolpidem and zopiclone have adverse-effect profiles similar to BZs but lack next day residual effects with bedtime dosing. Zaleplon is a fast-onset, rapidly eliminated medication that allows for dosing at bedtime or during the night with minimal concern for residual effects. In addition, the BZ-associated problems of tolerance and rebound effects are not evident with long-term zaleplon use. The pharmacokinetic profile of zaleplon has the potential to allow for the treatment of symptoms of sleeplessness when they occur, an approach that could replace the standard practice of always treating in anticipation of a problem. PMID- 11219328 TI - New perspectives on the pharmacologic management of insomnia. PMID- 11219330 TI - The relationship between psychiatric diseases and insomnia. AB - Sleep difficulties affect about one-third of American adults, yet these symptoms are not often addressed by patients and their physicians. Unresolved insomnia that impairs daytime function may be associated with significant psychiatric morbidity, predominantly major depression. Clinicians who are aware that these disorders frequently co-exist will be able to facilitate prompt diagnosis and initiate appropriate pharmacotherapeutic intervention. Antidepressant therapies may interfere with sleep quality; therefore, the management of insomnia in depressed patients should be addressed separately. Traditionally, benzodiazepines have been prescribed to treat sleep disturbances, but certain drugs in this class have limited benefits due to residual sedative effects that impair cognitive function, memory and general daytime performance. Zaleplon, a new, quick-acting, non-benzodiazepine sleep medication, may be clinically advantageous in promoting sleep without residual impairment. PMID- 11219329 TI - Individualizing therapy for early, middle-of-the-night and late-night insomnia. AB - Many patients with insomnia describe their sleep problems as an inability to remain asleep throughout the night, resulting in next-day fatigue that may adversely affect daytime functioning. To be most effective, insomnia treatment should be tailored to resolving underlying causes of the condition and managing specific sleep complaints. Therefore, hypnotic therapy administered prior to bedtime, as is currently recommended for most compounds, is not appropriate for all insomnia patients. Ideally, behavioral interventions should be combined with a rapid-acting agent that can be administered at virtually any time during the night without producing residual effects the following day. Zaleplon, a new non benzodiazepine sleep medication, provides the clinician with an effective and safe pharmacotherapeutic option for insomnia management. Its rapid rates of absorption and elimination allow for treatment of symptoms when they occur, either at bedtime or later at night, without incurring significant risk for the development of next-day impairment of psychomotor and cognitive functioning. PMID- 11219331 TI - Efficacy and safety of zaleplon at peak plasma levels. AB - Zaleplon is a non-benzodiazepine sleep medication that shows efficacy as a sleep inducer comparable to that of other hypnotics but with significantly fewer residual effects. In addition, evaluations of psychomotor or memory function at zaleplon peak plasma levels show much less impairment than noted with other hypnotics, suggesting an improved benefit-to-risk profile for zaleplon compared with older available agents. Thus, zaleplon can be used to treat symptoms of insomnia when they occur without the concern of next-day psychomotor or memory impairment, whether administered at bedtime or later during the night. Such an approach permits physicians to reformulate their strategies for safe and effective management of sleeplessness. PMID- 11219339 TI - The significance of surveillance and reporting on the prevention and control of equine diseases. AB - Examples of equine disease surveillance at the local, regional, national and international level are discussed in this article. Reporting systems at each level are also considered, and the increasing importance of laboratory confirmed diagnoses is emphasized. The need to develop national disease reporting systems is addressed, particularly with respect to conforming to international trading standards. PMID- 11219340 TI - Equine protozoal myeloencephalitis. AB - Recent advances in the understanding of the parasite life cycle, epidemiology, clinical signs, diagnosis, treatment, and prevention of EPM are reviewed. The NAHMS Equine '98 study and a controlled retrospective study from The Ohio State University College of Veterinary Medicine identified a number of risk factors associated with development of the disease. The national annual incidence of EPM was 1% or less depending on the primary use of the animals. Increased disease risk was associated with age (1-5 and > 13 years of age), season (lowest in winter months and increasing with ambient temperature), previous stressful events, the presence of opossums, the use of nonsurface water drinking systems, and failure to restrict wildlife access to feed. Horses that received treatment were 10 times more likely to improve, and those that improved were 50 times more likely to survive. A number of recent studies confirmed that horses can be experimentally infected with S. neurona; however, large numbers of sporocysts are apparently necessary to achieve infection, and clinical signs and abnormal CNS histology are only seen inconsistently. Results suggest that CNS infection and positive CSF immunoblot findings may be transient phenomena among naturally infected horses. Although immunosuppression may be involved in the development of EPM, some element of the immune response seems to be necessary for the development of clinical signs. Use of the standard immunoblot test for the detection of anti-S. neurona antibodies in CSF continues to provide the most useful adjunct to a detailed neurologic examination for the diagnosis of EPM. Test sensitivity and specificity were 89% in 295 horses euthanatized because of neurologic disease, of which 123 were confirmed cases of EPM. The PPV was 85%, and the NVP was 92%. A number of promising new EPM treatments are under investigation. In addition to standard SDZ/PYR therapy, toltrazuril, ponazuril, diclazuril, and NTZ have shown promise as possible alternatives. PMID- 11219341 TI - West Nile encephalitis. AB - WNV encephalitis in horses, previously reported in Africa, Asia, and Europe, occurred for the first time in the Western Hemisphere in 1999. The causative agent, WNV, is a flavivirus maintained in nature by a bird-mosquito cycle. The disease in horses is manifested primarily by ataxia of variable severity. Outbreaks of encephalitis may have a case fatality rate in excess of 40%, although this virus infection is inapparent in some horses. Early evidence indicates that WNV has overwintered in the northeastern United States and poses a threat for future disease occurrences in horses. No vaccine is available to protect against WNV infection in horses; disease control is predicated on mosquito abatement. PMID- 11219342 TI - Emergent causes of placentitis and abortion. AB - The clinical signs, laboratory findings, diagnosis, epidemiology, treatment, and prevention and control of two emerging causes of placentitis and abortion in horses are described in this article. Leptospirosis has been reported as a significant cause of fetal loss in horses in Kentucky, Northern Ireland, and England. Most abortions result from infection by serovars kennewicki or bratislava. Nocardioform placentitis has become the most common cause of placentitis in central Kentucky horses. Nocardioform placentitis is associated with infection by unnamed, gram-positive, filamentous, branching bacteria, and is characterized by distinctive changes in the placental membranes. PMID- 11219343 TI - Vesicular stomatitis and other vesicular, erosive, and ulcerative diseases of horses. AB - Physical trauma, dietary factors, certain toxins, immune mediated disorders, and vesicular stomatitis virus (VSV) infection are known causes of stomatitis in horses. There is evidence that some outbreaks of equine stomatitis are caused by as yet unidentified infectious agents. It remains to be determined whether stomatitis is an emerging equine infectious disease, or if the increase in reported cases is simply the result of greater public awareness as a consequence of widespread outbreaks of VSV in the southwestern United States in recent years. Focused laboratory and epidemiological studies are necessary to more adequately define non-VS related infectious and noninfectious causes of equine stomatitis. PMID- 11219345 TI - Ehrlichial diseases. AB - Equine granulocytic and monocytic ehrlichiosis caused by Ehrlichia equi and E. risticii, respectively, are seasonal diseases in horses that occur throughout the United States E. equi is transmitted by lxodes ticks and causes high fever, depression, anorexia, limb edema, petechiation, icterus, ataxia, and stiffness in gait. E. risticii, also known as the agent of Potomac horse fever, causes a febrile illness with a colitis of variable severity. Its occurrence is associated with aquatic habitats. The natural route of transmission is oral, through the ingestion of E. risticii infected trematode stages either free in water or in an intermediate host, such as aquatic animals. PMID- 11219344 TI - Clostridial enterocolitis. AB - Equine clostridial enterocolitis is being recognized with increasing frequency. It has been identified in foals with diarrhea, antibiotic-associated enterocolitis, or nosocomial enterocolitis. The sporadic occurrence of clostridial enterocolitis, the variety of types of clostridia involved, and the difficulty of experimentally reproducing the disease suggest that it is a poorly defined multifactorial syndrome. The risk factors associated with susceptibility to colonization and progressive infection are largely based on anecdotal observations and extrapolation from human studies. Quantitative studies are needed to decipher the complex interactions between host and indigenous microflora that provide for and maintain a healthy colonization resistance environment. It seems that such studies might be more beneficial in furthering our understanding of the pathogenesis of clostridial enterocolitis than attempting to implicate another agent or toxin as the sole cause of the disease in equids. Treatment protocols that interrupt the pathogenesis of the disease need to be devised and critically evaluated to complement the present protocols emphasizing supportive care. Perhaps it is time to consider clostridial enterocolitis as yet another consequence of the use of antimicrobials analogous to the selective pressures that result in the emergence of multiple drug resistant pathogens. PMID- 11219346 TI - Larval cyathostomiasis. AB - Over the past few years, cyathostomiasis has become increasingly recognized as a clinical problem of horses in the United States. Clinical cyathostomiasis has been reported frequently in Europe for a considerable time. This clinical syndrome is usually related to the sudden release of large numbers of the larval stages of small strongyles from the mucosa of the large intestine. Typical clinical signs include diarrhea, ventral abdominal edema, pyrexia, colic, weight loss, and poor body condition. Hypoalbuminemia and the presence of large numbers of small strongyles being passed in the feces are also characteristic features of the disease. The disease may occur seasonally in late winter and early spring or after drug treatment to remove the luminal stages of small strongyles. Two commercially available drugs, moxidectin and fenbendazole, have been shown to be effective against the encysted larval stages of the parasites. Drug resistance of small strongyles to all classes of currently available antiparasitic compounds except the macrocyclic lactones (ivermectin and moxidectin) is a limiting factor in controlling these parasites and may result in an increased prevalence of clinical cyathostomiasis over time. PMID- 11219347 TI - Antimicrobic and anthelmintic resistance. AB - Antimicrobial and anthelmintic resistance are growing issues for the equine practitioner. The development of antimicrobial or anthelmintic resistance is a source of significant concern because of increased frequency of treatment failures and increased treatment costs. In addition, antimicrobial resistance may have important consequences for public health. Only through judicious use can the efficacy of antimicrobials and anthelmintics be prolonged. This article discusses the development of resistance and suggestions for control. PMID- 11219348 TI - Factors influencing the international spread of equine diseases. AB - In an era of increasing globalization, the risk of spread of infectious diseases in humans and animals, including equids, has never been greater. International movement of equids and trade in semen are the most important factors responsible for the dissemination of various equine pathogens. Other factors that can or do have the potential to influence the global distribution of equine infectious diseases include: multinational trade agreements, emergent diseases, mutation of pathogens, climate related phenomena, migration of amplifying/reservoir hosts or vectors, availability of new vectors, vaccine contamination and agroterrorism. The relative importance of each of these factors is considered in relation to the spread of equine diseases. PMID- 11219349 TI - Venezuelan equine encephalomyelitis. AB - The emergence of epidemic VEE viruses has been reported ever since the virus was first described; this phenomenon is likely to continue to occur because of the high mutation rate of these RNA viruses. A vaccine that was first developed by the US Military for human use has proved helpful in curtailing the spread of VEE virus during epizootics of the disease in equids but not during human epidemics. It has not, however, eliminated the source of these highly pathogenic and transmissible viruses. Occurrences of VEE in equids in Mexico in recent years suggest that the present vaccine is not effective in interrupting transmission of new epizootic viruses arising from what were previously known as avirulent enzootic cycles. Future vaccines against VEE should be based on immunogens derived from enzootic viruses to interrupt VEE virus transmission at the source itself rather than waiting for virulent phenotypes of VEE virus to emerge. PMID- 11219350 TI - Japanese encephalitis. AB - Japanese encephalitis (JE) virus is a mosquito-borne flavivirus that can cause encephalitis and death in horses and humans. It is an emerging disease of international concern because it has been spreading into previously nonendemic areas. Major epidemics may occur where the virus moves into new areas, but many infections are subclinical. This article presents information on the virus, its epidemiology, and what little information has been published on the disease in horses. The methods available for the diagnosis and control of JE are described and issues raised, particularly for those countries faced with the threat of imminent incursions as the virus extends its range. PMID- 11219351 TI - Borna disease in horses. AB - Borna disease is a sporadically occurring, progressive viral polioencephalomyelitis that primarily affects horses and sheep. The etiological agent, Borna disease virus (BDV), is an enveloped, single-stranded RNA virus that has been classified in the new virus family Bornaviridae within the order Mononegavirales. Serological evidence of BDV infection has been found in an increasing number of countries throughout the world. After an incubation period lasting a few weeks to several months, BDV infection can cause locomotor and sensory dysfunction followed by paralysis and death. Borna disease is the result of a virus-induced immunopathological reaction. BDV-specific antibodies and viral RNA have been found in humans with various psychiatric disorders. PMID- 11219352 TI - Hendra and Nipah virus infections. AB - The most important clinical and pathological manifestation of Hendra virus infection in horses and humans is that of severe interstitial pneumonia caused by viral infection of small blood vessels. The virus is also capable of causing nervous disease. Hendra virus is not contagious in horses and is spread by close contact with body fluids, such as froth from infected lungs. Diagnosis should be based on the laboratory examination of blood, lung, kidney, spleen, and, if nervous signs are present, also of the brain. Evidence of infection with the more recently identified and related Nipah virus was found in the brain of one horse in which there was inflammation of the meningeal blood vessels. Fruit bats, especially Pteropus s., have been incriminated as the natural and reservoir hosts of both Hendra and Nipah viruses. PMID- 11219353 TI - Getah virus as an equine pathogen. AB - Getah virus is a member of the genus Alphavirus in the family Togaviridae and has been frequently isolated from mosquitoes. Seroepizootiologic studies indicate that the virus is mosquito-borne and widespread, ranging from Eurasia to southeast and far eastern Asia, the Pacific islands, and Australasia. The natural host animal of the virus was not known until the first recognized occurrence of Getah virus infection among racehorses in two training centers in Japan in 1978. Outbreaks of clinical disease due to Getah virus infection occur infrequently, and only one outbreak has been reported outside Japan; this was in India in 1990. Clinical signs of the disease are mild and nonlife-threatening and are characterized by pyrexia, edema of the hind limbs, swelling of the submandibular lymph nodes, and urticarial rash, as reported in the 1978 epizootic. The morbidity was 37.9% (722 of 1903 horses) in one training center, with 96% of 722 affected horses making a full clinical recovery within a week without any significant sequelae. Antibodies against Getah virus were detected in 61.2% (172 of 281) and 55.8% (254 of 455) of horses at two training centers, respectively. Virus isolation can be attempted in VERO, RK-13, BHK-21, and many other cell lines as well as in suckling mouse brain. Blood plasma collected from suspect cases of infection at the onset of pyrexia is the specimen of choice. A diagnosis of Getah virus infection can also be confirmed serologically based on testing acute and convalescent phase sera by using SN, CF, HI, and ELISA tests. An inactivated vaccine is available for the prevention and control of Getah virus infection in horses in Japan. PMID- 11219354 TI - Venerable or vulnerable? Ageism in health care. PMID- 11219355 TI - Cost analysis of a hospital-at-home initiative using discrete event simulation. AB - OBJECTIVES: To examine whether, from a National Health Service (NHS) and local authority social services' viewpoint, a hospital-at-home service was cost saving compared with conventional inpatient care. METHODS: The subjects of this part retrospective and part-prospective cost analysis were 51 elderly medical and orthopaedic surgical patients assessed at Hillingdon Hospital, West London, as being suitable for hospital-at-home care. Thirty patients received hospital-at home care, provided for up to 14 days, while 21 patients remained in hospital and received standard inpatient care. All direct costs to the NHS hospital, community health services' provider and social services' department during the initial episode of care and the three months after discharge were collected for each group of patients. Costs and clinical event data were entered in a discrete event simulation model which generated baseline results. Uncertainty surrounding the model's parameters was explored using sensitivity analysis. RESULTS: The baseline simulation performed with 1000 patients in each group showed the mean cost per patient for hospital-at-home care and three-month follow-up to be around three fifths the mean cost per patient of inpatient care and follow-up. Most of the excess cost in the inpatient group was attributable to the initial period of hospitalisation. Under all assumptions used in the sensitivity analysis, the hospital-at-home service was less costly. CONCLUSIONS: For elderly patients assessed as needing no more than 14 days of hospital care, hospital-at-home care is cost saving to health and social care agencies when compared with conventional inpatient care. PMID- 11219357 TI - It ain't what you do but the way that you do it. PMID- 11219356 TI - Implementation of evidence-based medicine: evaluation of the Promoting Action on Clinical Effectiveness programme. AB - OBJECTIVES: To evaluate the Promoting Action on Clinical Effectiveness (PACE) programme, which sought to implement clinically effective practice in 16 local sites. METHODS: 182 semi-structured interviews, usually by telephone, with project team members, clinicians, and senior managers and representatives from the Department of Health and the King's Fund. RESULTS: The most influential factors were strong evidence, supportive opinion leaders and integration within a committed organization; without these factors, projects had little chance of success. Other factors (context analysis, professional involvement and good project management) emerged as important, supporting processes; their presence might be an additional help, but on their own they would not be enough to initiate change. A serious problem with any of them could have a strong adverse impact. CONCLUSIONS: Although there is no simple formula for the factors that ensure successful implementation of research-based improvements to clinical practice, certain principles do seem to help. Time and resource need to be devoted to a period of local negotiation and adaptation of good research evidence based on a careful understanding of the local context, in which opinion leader influence is an important component of a well managed and preferably well integrated process of change. PMID- 11219358 TI - Can simulation be used to reduce errors in health care delivery? The hospital drug distribution system. AB - OBJECTIVES: To construct a simulation model of the hospital drug distribution system, to evaluate the effects of different changes to the system on unavailability-related medication administration errors (U-MAEs), to test the most promising system in a controlled trial and to explore the model's validity. METHODS: A discrete-event simulation model of the drug distribution system was constructed, using data collected on a vascular surgery ward and a renal medicine ward as model inputs. The model's output was the U-MAE rate. The model was used to explore the effects on U-MAEs of different changes to the system. One of the changes predicted to reduce U-MAEs, a patients' own drugs scheme, was introduced on each study ward; U-MAE rates were measured using observations before and after its introduction and compared with those predicted by the model. RESULTS: The model predicted that the introduction of a patients' own drugs system would reduce unavailability-related errors on each ward; in practice, there was a slight decrease on the medical ward but an increase on the surgical ward. Reasons for these findings were explored and four contributing factors identified. Three of these related to failure to follow hospital procedures, the fourth to an issue for which no policy existed. If these factors had been taken into account, the error rates predicted by the model would have been similar to those observed. CONCLUSIONS: Simulation modelling is a potentially useful approach to the study of U-MAEs, although care must be taken to ensure that such models reflect actual practice rather than stated policy. PMID- 11219359 TI - Developing appropriate measures of the benefits of complementary and alternative medicine. AB - Complementary and alternative medicine (CAM) is growing in popularity and consumes increasing amounts of resources. Economic evaluations such as cost effectiveness analyses (CEAs) are intended to inform decision-makers about the relative efficiency of different interventions, including CAM. To be generalizable, economic evaluations should use the same metric to assess health benefits--e.g. quality-adjusted life years (QALYs). However, the recurrent conditions for which CAM is typically used suggest that the health benefits of CAM will manifest themselves primarily as quality-of-life improvements that appear in CEA as 'utilities' attached to health states. Therefore, appropriate utility measures will be critical to the production of valid CEAs of CAM therapies. Some economists assert that the process of health care, as well as its outcome, can contribute to patient utility. This essay argues that process utility is especially relevant to CAM; accurate assessment of process utility will be important to valid economic evaluations of CAM; existing utility assessment methods do not directly account for process utility; and, therefore, techniques such as qualitative analysis that can inform more appropriate and complete assessments of the benefits of CAM should be explored. The heterogeneity of CAM modalities suggests that the arguments made in this essay will apply with similar force to economic evaluation of conventional therapies with which CAM is likely to be compared. PMID- 11219361 TI - Roemer's effect reconsidered. PMID- 11219360 TI - Impact of payment method on behaviour of primary care physicians: a systematic review. AB - OBJECTIVE: To review the impact of payment systems on the behaviour of primary care physicians. METHODS: All randomised trials, controlled before and after studies, and interrupted time series studies that compared capitation, salary, fee-for-service or target payments (mixed or separately) that were identified by computerised searches of the literature. Methodological quality assessment and data extraction were undertaken independently by two reviewers using a data checklist. Study results were qualitatively analysed. RESULTS: Six studies met the inclusion criteria. There was considerable variation in the quality of reporting, study setting and the range of outcomes measured. Fee-for-service resulted in a higher quantity of primary care services provided compared with capitation but the evidence of the impact on the quantity of secondary care services was mixed. Fee-for-service resulted in more patient visits, greater continuity of care, higher compliance with a recommended number of visits, but lower patient satisfaction with access to a physician compared with salary payment. The evidence of the impact of target payment on immunisation rates was inconclusive. CONCLUSIONS: There is some evidence to suggest that how a primary care physician is paid does affect his/her behaviour but the generalisability of these studies is unknown. Most policy changes in the area of payment systems are inadequately informed by research. Future changes to doctor payment systems need to be rigorously evaluated. PMID- 11219362 TI - Does it matter who owns health facilities? AB - The rhetoric of governments 'steering not rowing' and of purchaser-provider splits is still part of the language of public sector reform throughout the world, despite some retreat in the National Health Service in the UK. Implementation of separation of purchaser and provider roles has often been associated with suggestions that the private sector is better able to manage hospitals. The evidence for this assertion is mixed, especially when possible quality differences are also considered. This essay suggests that the ownership question is a second-order issue and that policy-makers should ensure that existing public hospitals are funded in a way that encourages efficiency. PMID- 11219364 TI - Alcoholism and schizophrenia. PMID- 11219363 TI - Inequality in the geographical distribution of general practitioners in England and Wales 1974-1995. AB - OBJECTIVES: To compare geographical inequality in the distribution of general practitioners (GPs), other resources and mortality around 1995 in England and Wales; to measure trends between 1974 and 1995 in inequality of GP distribution; to examine the implications of different need adjustments and inequality measures on the degree of geographic inequality; and to analyse the impact of policies (increased supply, area inducements and entry regulation) on inequality. METHODS: Measurement of relative inequality (decile ratio, Gini coefficient, Atkinson index) and absolute inequality (standard deviation) in the ratio of GPs to need adjusted population in former Family Practitioner Committee/Family Health Services Authority areas each year from 1974 to 1995; and relative inequality across areas in the distributions of income, other resources and standardised mortality ratios (SMRs) around 1995. Regression of 1995 GP/population ratios on 1974 ratios. Application of equalising net advantages location model to GP distribution. RESULTS: Inequality in the distribution of GPs in 1995 was less than inequality in other primary care resources, but greater than inequalities in disposable income, SMRs, primary school expenditure, and hospital and community health services expenditure. The decile ratio shows little change between 1974 and 1995. Gini and Atkinson inequality indices indicate some reduction in inequality between 1974 and 1980, but little change thereafter. The standard deviation of need-adjusted provision increased over the period. Areas that had the lowest GP provision in 1974 tended to have the lowest in 1995. CONCLUSIONS: The choice between relative and absolute inequality measures and, to a lesser extent, the method of adjusting for need affect conclusions about the trend in inequality. Both types of measure and most need adjustments suggest that the policies adopted did not lead to a reduction in inequality over the period. Interactions between policies may reduce their overall effectiveness. PMID- 11219365 TI - Drug use and young people: why is co-morbidity research so important? PMID- 11219366 TI - The effects of adolescent cannabis use on educational attainment: a review. AB - This paper reviews research examining the link between cannabis use and educational attainment among youth. Cross-sectional studies have revealed significant associations between cannabis use and a range of measures of educational performance including lower grade point average, less satisfaction with school, negative attitudes to school, increased rates of school absenteeism and poor school performance. However, results of cross-sectional studies cannot be used to determine whether cannabis use causes poor educational performance, poor educational performance is a cause of cannabis use or whether both outcomes are a reflection of common risk factors. Nonetheless, a number of prospective longitudinal studies have indicated that early cannabis use may significantly increase risks of subsequent poor school performance and, in particular, early school leaving. This association has remained after control for a wide range of prospectively assessed covariates. Possible mechanisms underlying an association between early cannabis use and educational attainment include the possibility that cannabis use induces an 'amotivational syndrome' or that cannabis use causes cognitive impairment. However, there appears to be relatively little empirical support for these hypotheses. It is proposed that the link between early cannabis use and educational attainment arises because of the social context within which cannabis is used. In particular, early cannabis use appears to be associated with the adoption of an anti-conventional lifestyle characterized by affiliations with delinquent and substance using peers, and the precocious adoption of adult roles including early school leaving, leaving the parental home and early parenthood. PMID- 11219368 TI - Lethal methadone intoxications in Geneva, Switzerland, from 1994 to 1998. AB - AIMS: To estimate the number of methadone lethal intoxications in Geneva from 1994 to 1998, where the number of patients in methadone treatment has more than doubled since 1990. DESIGN: Retrospective study of all toxicological, autopsy and clinical data. SETTING: The Geneva Department of Forensic Medicine. PARTICIPANTS: All suspected overdose deaths in Geneva from 1994 to 1998. Cases were selected on the basis that the only cause of death was a potentially lethal drug concentration in the postmortem blood sample. MEASUREMENT: Toxicology and autopsy findings, clinical and drug history. FINDINGS: There were 106 lethal drug intoxications over the period. The overall number of drug intoxication deaths went from 33 in 1994 to nine in 1998. Thirty-six cases had methadone identified in their blood. All the 36 cases but one had medications or other drugs used illicitly present in the blood or urine. Of these 36 cases, 21 were attributed to methadone lethal intoxication. Only seven of these 21 decedents were enrolled in a methadone programmes. The number of deaths attributed to methadone intoxication ranged from three to five per year. CONCLUSION: Most lethal methadone intoxication is due to diverted or illegal methadone in association with medications or other drugs used illicitly. Furthermore, the increase in methadone prescription under strict medical control with health measures aimed at drug abuse prevention did not lead, in our study, to an increase of methadone lethal intoxication and may have been partly responsible for the large decrease of overall drug intoxication deaths during the time of our study. PMID- 11219367 TI - Randomized trial of supervised injectable versus oral methadone maintenance: report of feasibility and 6-month outcome. AB - AIM: To assess the feasibility of a randomized clinical trial of supervised injectable versus oral methadone maintenance and to assess medium-term treatment outcomes. DESIGN: Randomized clinical trial of supervised injectable versus supervised oral methadone maintenance treatment (MMT). Trial participants were dependent illicit opiate injectors allocated at intake to supervised injectable or oral methadone maintenance treatment. SETTING: Specialist addictions treatment centre in South London. SUBJECTS: Forty dependent illicit opiate injectors seeking methadone maintenance treatment. INTERVENTIONS: Daily supervised injectable and oral methadone maintenance, delivered at the treatment centre. MAIN OUTCOME MEASURES: Frequency of illicit heroin use and frequency of illicit drug injecting during 30 days before intake to treatment and prior to 6-month follow-up. SECONDARY OUTCOME MEASURES: frequency of use of illicit methadone, crack cocaine, benzodiazepines and alcohol, physical and psychological health symptoms and acquisitive crime. RESULTS: Injectable and oral MMT were both generally acceptable to the study participants: there was a high level of agreement to enter the randomized trial, and subsequent retention in treatment was good. The average number of days of illicit heroin use reduced from 22.2 to 7.6 for the injectable MMT group and from 22.4 to 8.7 for the oral MMT group. The average number of days of illicit injecting reduced from 25.7 to 10.8 days for the injectable group and from 20.1 to 11.9 days for the oral group. Patients' physical and psychological health symptoms and involvement in acquisitive crime also reduced in both groups. Treatment satisfaction ratings at follow-up were higher among patients in the injectable MMT group. The ratio for the actual medication costs between injectable and oral MMT was 6.8:1, and for the direct operational costs was 4.7:1. There was some evidence of a differential patient response with greater reductions in heroin use occurring among patients who were daily illicit injectors and had poorer psychological and physical health (at entry) who were allocated to injectable MMT. CONCLUSIONS: Conduct of the trial has demonstrated that it is feasible to implement supervised injectable methadone maintenance treatment in the context of (although separate from) a specialist oral methadone maintenance service. Patients assigned to receive either supervised injectable or oral MMT had broadly equivalent, positive during treatment outcomes at 6-month follow-up. Future studies should seek to identify patient characteristics which are linked to good outcome in injectable MMT. Practical evidence-based guidance to physicians about determining which patients are more suitable for injectable MMT is urgently needed. PMID- 11219369 TI - Increased use of marijuana and other illicit drugs at US colleges in the 1990s: results of three national surveys. AB - AIMS: To examine rates and patterns of marijuana and other illicit drug use among different types of students and colleges in 1999, and changes in use since 1993. DESIGN: Self-administered mail survey (Harvard School of Public Health College Alcohol Study). SETTING: One hundred and nineteen nationally representative US 4 year colleges. PARTICIPANTS: A representative sample of 15,403 randomly selected students in 1993, 14,724 students in 1997 and 14,138 students in 1999. MEASUREMENTS: Self-reports of marijuana and other illicit drug use in the past 30 days and in the past year, cigarette use, drinking behavior, and age of initiation of smoking, drinking and using marijuana. FINDINGS: The prevalence of past 30-day marijuana use rose from 12.9% to 15.7% between 1993 and 1999, an increase of 22%. Almost all of this change occurred by 1997. An increase was observed at 66% of the 119 colleges. The prevalence of 30-day and annual marijuana use increased in nearly all student demographic subgroups except for Hispanic students, and at all types of colleges except for colleges with low binge drinking rates. Rates of illicit drug use in the past 30 days increased slightly for other illicit drugs in the 4-year interval except for LSD. Nine out of 10 students (91%) who used marijuana in the past 30 days used other illicit drugs, smoked cigarettes and/or engaged in binge drinking. Of students who used any other illicit drug in the past 30 days, 87% used another substance or binge drank. Twenty nine per cent of past 30-day marijuana users first used marijuana and 34% began to use marijuana regularly at or after the age of 18, when most were in college. CONCLUSIONS: Use of marijuana and other illicit drugs has increased on campuses across the United States in most student subgroups and all types of colleges. This may reflect earlier increases in middle schools and secondary schools among this cohort. However, nearly one-third of students initiated marijuana use in college and one of three began to use it regularly. Intervention efforts should be directed at college students, as well as secondary school students. PMID- 11219370 TI - The respiratory effects of cannabis dependence in young adults. AB - AIM: To evaluate the relationship between cannabis dependence and respiratory symptoms and lung function in young adults, while controlling for the effects of tobacco smoking. SETTING AND PARTICIPANTS: Nine hundred and forty-three young adults from a birth cohort of 1037 subjects born in Dunedin, New Zealand in 1972/1973 were studied at age 21. MEASUREMENTS: Standardized respiratory symptom questionnaires were administered. Spirometry and methacholine challenge tests were undertaken. Cannabis dependence was determined using DSM-III-R criteria. Descriptive analyses and comparisons between cannabis-dependent, tobacco-smoking and non-smoking groups were undertaken. Adjusted odds ratios for respiratory symptoms, lung function and airway hyper-responsiveness (PC20) were measured. FINDINGS: Ninety-one subjects (9.7%) were cannabis-dependent and 264 (28.1%) were current tobacco smokers. After controlling for tobacco use, respiratory symptoms associated with cannabis dependence included: wheezing apart from colds, exercise induced shortness of breath, nocturnal wakening with chest tightness and early morning sputum production. These were increased by 61%, 65%, 72% (all p < 0.05) and 144% (p < 0.01) respectively, compared to non-tobacco smokers. The frequency of respiratory symptoms in cannabis-dependent subjects was similar to tobacco smokers of 1-10 cigarettes/day. The proportion of cannabis-dependent study members with an FEV1/FVC ratio of < 80% was 36% compared to 20% for non-smokers (p = 0.04). These outcomes occurred independently of co-existing bronchial asthma. CONCLUSION: Significant respiratory symptoms and changes in spirometry occur in cannabis-dependent individuals at age 21 years, even although the cannabis smoking history is of relatively short duration. PMID- 11219371 TI - Initiation and progression of cannabis use in a population-based Australian adolescent longitudinal study. AB - AIMS: To examine predictors of cannabis use initiation, continuity and progression to daily use in adolescents. DESIGN: Population-based cohort study over 3 years with 6 waves of data collection. PARTICIPANTS: 2032 students, initially aged 14-15 years, from 44 secondary schools in the state of Victoria, Australia. MEASUREMENTS: Self-report cannabis use was categorized on four levels (none, any, weekly, daily) and summarized as mid-school (waves 2/3) and late school (waves 4/5/6) use. Background, school environment, mid-school peer use and individual characteristics were assessed. FINDINGS: Peer cannabis use, daily smoking, alcohol use, antisocial behaviour and high rates of school-level cannabis use were associated with mid-school cannabis use and independently predicted late-school uptake. Cannabis use persisted into late-school use in 80% of all mid-school users. Persisting cannabis use from mid- to late-school was more likely in regular users (odds ratio (OR) 3.4), cigarette smokers (OR any smoking: 2.0, daily smoking: 3.3) and those reporting peer use (OR 2.1). Mid school peer use independently predicted incident late-school daily use in males (OR 6.5) while high-dose alcohol use (OR 6.1) and antisocial behaviour (OR 6.6) predicted incident late-school daily use in females. CONCLUSIONS: Most cannabis use remained occasional during adolescence but escalation to potentially harmful daily use in the late-school period occurred in 12% of early users. Transition was more likely in males, for whom availability and peer use were determinants. In contrast, females with multiple extreme behaviours were more likely to become daily users. Cigarette smoking was an important predictor of both initiation and persisting cannabis use. PMID- 11219372 TI - Further validation and development of a screening instrument for the assessment of substance misuse in adolescents. AB - AIM: The aim of this study was to investigate the validity of the Substance Misuse in Adolescence Questionnaire, which has been proposed as a screening instrument for problem drug use in adolescents. PARTICIPANTS AND SETTING: The participants in the study were 4544 11-16-year-olds attending eight secondary schools located in the north-west midlands of England. PROCEDURE: Participants completed an anonymous self-report questionnaire that incorporated a modified version of the SMAQ (the Assessment of Substance Misuse in Adolescence: ASMA), together with other questions relating to substance use and associated issues. RESULTS: The ASMA showed good reliability, both within the overall sample of respondents, and in a drug-using subsample. Principal-components analysis returned a single factor when applied either to the whole sample or to the drug using subsample; 1.4% of respondents met a criterion equivalent to that proposed by Swadi (1997) for 'problem drug use' (ASMA > 12). A further 6.4% reached a threshold for potentially problematic drug use (ASMA > 8) and could be considered 'at risk'. In regression analyses, ASMA scores were predicted by drug-related variables, and by low resistance to peer influence (RPI), but not by alcohol related variables. The highest ASMA scores and lowest levels of RPI were found in heroin users. Respondents' perceptions of their future risk of drug or alcohol problems were predicted by RPI and by frequency of drug use and drunkenness. CONCLUSIONS: The ASMA may be a useful screening instrument for identifying problem drug use in adolescents unknown to treatment services. PMID- 11219373 TI - Joint heavy use of alcohol, cigarettes and coffee and the risk of suicide. AB - AIMS: To estimate the relationship between joint heavy use of alcohol, cigarettes and coffee, and the risk of suicide in a general population with high rate of suicide. DESIGN: Prospective cohort analyses. SETTING: Finland. PARTICIPANTS: Data from 36,689 adult (age range 25-64 years) men and women who participated in the population surveys between 1972 and 1992. MEASUREMENTS: The mortality of the cohort was monitored for a mean of 14.4 years, which yielded 169 suicides. Criteria for heavy use of each psychoactive substance were defined as follows: alcohol (> 120 g/week), cigarettes (> or = 21/day) and coffee (> or = seven cups/day). FINDINGS: About half the men and 80% of the women did not use any of the psychoactive substances heavily. Every third man and every fifth woman used one substance heavily, and the prevalence for those who exceeded criteria for joint heavy use of two substances was 9% for men and 1% for women. Joint heavy use of all three substances was rare. The adjusted relative risk of suicide increased linearly with increasing level of joint heavy use of alcohol, cigarettes and coffee. Among subjects with heavy use of one substance the risk was 1.55 (95% CI = 1.10, 2.18), with joint heavy use of two substances 2.22 (95% CI = 1.37, 3.61), and with joint heavy use of all three substances 3.99 (95% CI = 1.80, 8.84) compared with no heavy use. CONCLUSIONS: Clustering of the heavy use of alcohol, cigarettes and coffee could serve as a new marker for increased risk of suicide. PMID- 11219374 TI - Indigenous Australians and liquor licensing restrictions: comments. PMID- 11219375 TI - Indigenous Australians and liquor licensing--some additional comments. PMID- 11219376 TI - The risk of injury and alcohol consumption. PMID- 11219377 TI - DUI risk screening instruments. PMID- 11219378 TI - Does working without theorizing make life endurable? PMID- 11219379 TI - An excellent springboard. PMID- 11219380 TI - Testing CBT mechanisms of action: humans behave in a more complex way than our treatment studies would predict! PMID- 11219381 TI - Coping skills and Tiger Woods. PMID- 11219382 TI - Human genome row draws in journals. PMID- 11219383 TI - Tracing Nightingale's steps. PMID- 11219384 TI - Human science research in public health: the contribution and assessment of a qualitative approach. PMID- 11219385 TI - Bibliography. Current world literature. Arrhythmias. PMID- 11219386 TI - New functions for Cox-2 in health and disease: report of "The Third International Workshop on Cox-2", Ka'upelehu, Kona, Hawaii, USA, 30 August to 2 September 1999. PMID- 11219387 TI - Web reports. PMID- 11219388 TI - The Arthritis Research non-peer-review depository. PMID- 11219389 TI - Clonal expansion is a characteristic feature of the B-cell repetoire of patients with rheumatoid arthritis. AB - The present study was designed to analyze the level of B-cell clonal diversity in patients with rheumatoid arthritis by using HCDR3 (third complementarity determining region of the rearranged heavy chain variable region gene) length as a marker. A modified immunoglobulin VH gene fingerprinting method using either genomic DNA or complementary (c)DNA derived from B cells of the peripheral blood, synovial fluid, and tissues of several rheumatoid arthritis patients was employed. These assays permitted the detection and distinction of numerically expanded B-cell clones from activated but not numerically expanded B-cell clones. The present data suggest that B-cell clonal expansion is a common and characteristic feature of rheumatoid arthritis and that it occurs with increasing frequency from the blood to the synovial compartments, resulting in a narrowing of the clonal repertoire at the synovial level. These clonal expansions can involve resting, apparently memory B cells, as well as activated B cells. Furthermore, some of these individual expansions can persist over extended periods of time. These findings support the hypothesis that a chronic ongoing (auto)immune reaction is operative in rheumatoid arthritis and that this reaction, at least at the B-cell level, may be unique to each individual joint. A determination of the targets of these autoimmune reactions may provide valuable clues to help understand the immunopathogenesis of this disease PMID- 11219390 TI - Activation of synovial fibroblasts in rheumatoid arthritis: lack of Expression of the tumour suppressor PTEN at sites of invasive growth and destruction. AB - AIMS: PTEN is a novel tumour suppressor which exhibits tyrosine phosphatase activity as well as homology to the cytoskeletal proteins tensin and auxilin. Mutations of PTEN have been described in several human cancers and associated their invasiveness and metastatic properties. Although not malignant, rheumatoid arthritis synovial fibroblasts (RA-SF) exhibit certain tumour-like features such as attachment to cartilage and invasive growth. In the present study, we analyzed whether mutant transcripts of PTEN were present in RA-SF. In addition, we used in situ hybridization to study the expression of PTEN messenger (m)RNA in tissue samples of RA and normal individuals as well as in cultured RA-SF and in the severe combined immunodeficiency (SCID) mouse model of RA. Synovial tissue specimens were obtained from seven patients with RA and from two nonarthritic individuals. Total RNA was isolated from synovial fibroblasts and after first strand complementary (c)DNA synthesis, polymerase chain reaction (PCR) was performed to amplify a 1063 base pair PTEN fragment that encompassed the coding sequence of PTEN including the phosphatase domain and all mutation sites described so far. The PCR products were subcloned in Escherichia coli, and up to four clones were picked from each plate for automated sequencing. For in situ hybridization, digoxigenin-labelled PTEN-specific RNA probes were generated by in vitro transcription. For control in situ hybridization, a matrix metalloproteinase (MMP)-2-specific probe was prepared. To investigate the expression of PTEN in the absence of human macrophage or lymphocyte derived factors, we implanted RA-SF from three patients together with normal human cartilage under the renal capsule of SCID mice. After 60 days, mice were sacrificed, the implants removed and embedded into paraffin. RESULTS: PCR revealed the presence of the expected 1063 base pair PTEN fragment in all (9/9) cell cultures (Fig.1). No additional bands that could account for mutant PTEN variants were detected. Sequence analysis revealed 100% homology of all RA derived PTEN fragments to those from normal SF as well as to the published GenBank sequence (accession number U93051). However, in situ hybridization demonstrated considerable differences in the expression of PTEN mRNA within the lining and the sublining layers of RA synovial membranes. As shown in Figure 2a, no staining was observed within the lining layer which has been demonstrated to mediate degradation of cartilage and bone in RA. In contrast, abundant expression of PTEN mRNA was found in the sublining of all RA synovial tissues (Figs 2a and b). Normal synovial specimens showed homogeneous staining fo PTEN within the thin synovial membrane (Fig. 2c). In situ hybridization using the sense probe gave no specific staining (Fig. 2d). We also performed in situ hybridization on four of the seven cultured RA-SF and followed one cell line from the first to the sixth passage. Interestingly, only 40% of cultured RA-SF expressed PTEN mRNA (Fig. 3A), and the proportion of PTEN expressing cells did not change throughout the passages. In contrast, control experiments using a specific RNA probe fo MMP-2 revealed mRNA expression by nearly all cultured cells (Fig. 3B). As seen before, implantation of RA-SF into the SCID mice showed considerable cartilage degradation. Interestingly, only negligible PTEN expression was found in those RA SF aggressively invading the cartilage (Fig. 3c). In situ hybridization for MMP-2 showed abundant staining in these cells (Fig. 3d). DISCUSSION: Although this study found no evidence for mutations of PTEN in RA synovium, the observation that PTEN expression is lacking in the lining layer of RA synovium as well as in more that half of cultured RA-SF is of interest. It suggests that loss of PTEN function may not exclusively be caused by genetic alterations, yet at the same time links the low expression of PTEN to a phenotype of cells that have been shown to invade cartilage aggressively. It has been proposed that the tyrosine phosphatase activity of counteracting th actions o protein tyrosine kinases. As some studies have demonstrated an upregulation of tyrosine kinase activity in RA synovial cells, it might be speculated that the lack of PTEN expression in aggressive RA-SF contributes to the imbalance of tyrosine kinases and phosphatases in this disease. However, the extensive amino-terminal homology of the predicted protein to the cytoskeletal proteins tensin and auxilin suggests a complex regulatory function involving cellular adhesion molecules and phosphatase mediated signalling. The tyrosine phosphatase TEP1 has been shown to be identical to the protein encoded by PTEN, and gene transcription of TEP1 has been demonstrated to be downregulated by transforming growth factor (TGF)-beta. Therefore, it could be hypothesized that TGF-beta might be responsible for the downregulation of PTEN. Low expression of PTEN may belong to the features that distinguish between the activated phenotype of RA-SF and the sublining, proliferating but nondestructive cells. PMID- 11219391 TI - Mast cell activation and its relation to proinflammatory cytokine production in the rheumatoid lesion. AB - INTRODUCTION: Increased numbers of mast cells (MCs) are found in the synovial tissues and fluids of patients with rheumatoid arthritis (RA), and at sites of cartilage erosion. MC activation has been reported for a significant proportion of rheumatoid specimens. Because the MC contains potent mediators, including histamine, heparin, proteinases, leukotrienes and multifunctional cytokines, its potential contributions to the processes of inflammation and matrix degradation have recently become evident. Proinflammatory cytokines are important mediators of inflammation, immunity, proteolysis, cell recruitment and proliferation. Tumour necrosis factor (TNF) reportedly plays a pivotal role in the pathogenesis o RA, especially its ability to regulate interleukin (IL)-1beta expression, this being important for the induction of prostanoid and matrix metalloproteinase production by synovial fibroblasts and chondrocytes. IL-15 has been assigned numerous biological effects and has been assigned numerous biological effects and has been implicated as an important factor in TNF-alpha expression by monocyte/macrophages. Some in vitro studies have placed IL-15 upstream from TNF alpha in the cytokine cascade, suggesting an interdependence between TNF, IL-1 and IL-15 for the promotion of proinflammatory cytokine expression in the rheumatoid joint. AIMS: To examine the in situ relationships of TNF-alpha, IL 1beta and IL-15 in relation to MC activation in rheumatoid tissues by use of immunolocalization techniques; and to compare quantitatively the proinflammatory cytokine production by specific cell cultures and rheumatoid synovial explants with and without exposure to a MC secretagogue. MATERIALS AND METHODS: Samples of rheumatoid synovial tissue and cartilage-pannus junction were obtained from patients (n=15) with classic late-stage RA. Tissue sections were immunostained for MC (tryptase) and the proinflammatory cytokines IL-1, TNF-alpha and IL-15. Rheumatoid synovial tissue explants were cultured in Dulbecco's modified Eagles medium (DMEM) containing either the MC secretagogue rabbit antihuman immunoglobulin (Ig)E, or control rabbit IgG. Primary rheumatoid synovial cell cultures, human articular chondrocytes, synovial fibroblasts and synovial macrophages were prepared as described in the full article. Conditioned culture media from these cultures were collected and assayed for IL-1beta, TNF-alpha and IL-15 using enzyme-linked immunosorbent assay methodology. RESULTS: Immunohistological studies of rheumatoid synovial tissues have demonstrated local concentrations of MCs in most specimens of the rheumatoid lesion. Sites of MC activation were associated with localized oedema, and TNF-alpha, IL-1alpha and IL 1beta production by a proportion of mononuclear inflammatory cells. By contrast, no evidence was found for IL-15 production in tissue sites containing either intact or activated MCs, and IL-15 expression, when observed, bore no relation to tissue sites where TNF-alpha and IL-1beta were evident. The immunodetection of IL 15 was restricted to microfocal sites and was not typical of most junctional specimens, but was associated with a proportion of articular chondrocytes in a minority of junctional specimens. MC activation within synovial explant cultures was induced by the addition of polyclonal antibody to human IgE. MC activation significantly reduced the levels of TNF-alpha and IL-1beta released into the medium, this representing approximately 33% of control values. By contrast, MC activation had little effect of the levels of IL-15 released into the culture medium, the average value being very low in relation to the release of TNF-alpha and IL-1beta. Thus, induced MC activation brings about changes in the amounts of released tryptase, TNF-alpha and IL-1beta, but not of IL-15. Four preparations of primary rheumatoid synovial cell cultures produced more IL-1beta than TNF-alpha, with only modest values for IL-15 production, indicating that all three cytokines are produced and released as free ligands by these cultures. Of specific cell types that produced IL-15 in vitro, macrophages produced more than fibroblasts, which in turn produced more than chondrocytes. This demonstrates that all three cell types have the potential to produce IL-15 in situ. DISCUSSION: The biological consequences of MC activation in vivo are extremely complex, and in all probability relate to the release of various combinations of soluble and granular factors, as well as to the expression of appropriate receptors by neighbouring cells. The subsequent synthesis and release of cytokines such as TNF alpha and IL-1 may well follow at specific stages after activation, or may be an induced cytokine response by adjacent macrophagic or fibroblastic cells. However, because no IL-15 was detectable either in or around activated or intact MCs, and the induced MC activation explant study showed no change in IL-15 production, it seems unlikely that the expression of this cytokine is regulated by MCs. The immunohistochemistry (IHC) demonstration of IL-15 at sites of cartilage erosion, and especially by some chondrocytes of articular cartilage, showed no spatial relationship with either T cells or neutrophils, and suggests other functional properties in these locations. The lack of evidence for an in situ association of IL-15 with TNF and IL-1 does not support a role for IL-15 in a proinflammatory cytokine 'cascade', as proposed by other in vitro experiments. We believe that sufficient evidence is available, however, to suggest that MC activation makes a significant contribution to the pathophysiological processes of the rheumatoid lesion. PMID- 11219393 TI - Ninth Asia Pacific League of Associations for Rheumatology (APLAR) Congress, Beijing, China, 21-26 May, 2000. AB - The Congress covered the broad field of rheumatology, with participants from China, the Asia Pacific League of Associations of Rheumatology (APLAR) region and the rest of the world. The programme consisted of a mix of plenary lectures, concurrent symposia, workshops, free paper sessions and poster presentations. Basic sciences were well represented, with the general theme of inflammatory cytokines being of particular interest. One plenary lecture and a number of other presentations addressed the problem of atherosclerosis and rheumatic diseases. Diseases prominent in the region, such as Behcet's disease and Takayasu's disease, were represented with large series. Other areas of interest were musculoskeletal infections in HIV-positive patients and the management of spondyloarthritis. Although the use of the most recently developed drugs is restricted in the APLAR region because of cost factors, there were symposia on the latest pharmacological advances such as COX-2 technology, leflunomide and anti-tumour necrosis factor (TNF) therapy. PMID- 11219394 TI - Cell contact interactions in rheumatology, The Kennedy Institute for Rheumatology, London, UK, 1-2 June 2000. AB - The intricate interactions that regulate relationships between endogenous tissue cells and infiltrating immune cells in the rheumatic joint, particularly in rheumatoid arthritis (RA), were the subject of the meeting. A better understanding of these interactions might help to define intervention points that could be used to develop specific therapies. The presentations and discussions highlighted the fact that, once chronic inflammation is established, several proinflammatory loops involv9ing tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta can be defined. Direct cellular contact with stimulated T lymphocytes induces TNF-alpha and IL-1beta in monocytes which in turn induce functions in fibroblast-like synoviocytes. The latter include the production of stromal cell-derived factor-1alpha (SDF-1alpha) which enhances the expression of CD40L in T cells, which stimulates SDF-1alpha production in synoviocytes, which in turn protects T and B cells from apoptosis and enhances cell recruitment thus favoring inflammatory processes. IL-1beta and TNF-alpha also induce IL-15 in fibroblast like synoviocytes, which induces the production of IL-17 which in turn potentiates IL-1beta and TNF-alpha production in monocyte-macrophages. This underlies the importance of TNF-alpha and IL-1beta in RA pathogenesis, and helps explain the efficiency of agents blocking the activity of these cytokines in RA. Factors able to block the induction of cytokine production (such as apolipoprotein A-I [apo A-I] and interferon [IFN]-beta) might interfere more distally in the inflammatory process. Furthermore, stimulated T lymphocytes produce osteoclast differentiation factor (ODF), which triggers erosive functions of osteoclasts. Therefore, factors capable of affecting the level of T lymphocyte activation, such as IFN-beta, IL-15 antagonist, or SDF-1alpha antagonist, might be of interest in RA therapy. PMID- 11219392 TI - Interferon-gamma production in response to in vitro stimulation with collagen type II in rheumatoid arthritis is associated with HLA-DRB1(*)0401 and HLA-DQ8. AB - INTRODUCTION: Despite much work over past decades, whether antigen-specific immune reactions occur in rheumatoid arthritis (RA) and to what extent such reactions are directed towards joint-specific autoantigens is still questionable. One strong indicator for antigenic involvement in RA is the fact that certain major histocompatibility complex (MHC) class II genotypes [human leucocyte antigen (HLA)-DR4 and HLA-DR1[ predispose for the development of the disease [1]. In the present report, collagen type II (CII) was studied as a putative autoantigen on the basis of both clinical and experimental data that show an increased frequency of antibodies to CII in RA patients [2-4] and that show that CII can induce experimental arthritis [5]. It is evident from the literature that RA peripheral blood mononuclear cells (PBMCs) respond poorly to antigenic stimulation [6-8], and in particular evidence for a partial tolerization to CII has been presented [9]. The strategy of the present work has accordingly been to reinvestigate T-cell reactivity to CII in RA patients, to relate it to the response to commonly used recall antigens and to analyze interferon (IFN)-gamma responses as an alternative to proliferative responses. AIMS: To study cellular immune reactivity to CII in patients with RA and in healthy control individuals and to correlate this reactivity to HLA class II genotypes and to the presence of antibodies to CII in serum. METHODS: Forty-five patients who met the 1987 American college of Rheumatology classification criteria for RA [10] and 25 healthy control individuals of similar age and sex were included. Twenty-six of these patients who had low levels of anti-CII in serum were randomly chosen, whereas 19 patients with high anti-CII levels were identified by enzyme-linked immunosorbent assay (ELISA)-screening of 400 RA sera. Heparinized blood was density gradient separated and PBMCs were cultured at 1 x 10(6)/ml in RPMI-10% fetal calf serum with or without antigenic stimulation: native or denatured CII (100 microgram/ml), killed influenza virus (Vaxigrip, Pasteur Merieux, Lyon, France; diluted 1:1000) or purified protein derivative (PPD; 10 microgram/ml). CII was heat-denatured in 56 degrees C for 30 min. Cell supernatants were collected after 7 days and IFN-gamma contents were analyzed using ELISA. HLA-DR and HLA-DQ genotyping was performed utilizing a polymerase chain reaction-based technique with sequence-specific oligonucleotide probe hybridization. Nonparametric statistical analyses were utilized throughout the study. RESULTS: PBMCs from both RA patients and healthy control individuals responded with IFN gamma production to the same degree to stimulation with native and denatured CII (Fig. 1a), giving median stimulation indexes with native CII of 4.6 for RA patients and 5.4 for health control individuals, and with denatured CII of 2.9 for RA patients and 2.6 for healthy control individuals. RA patients with elevated levels of anti-CII had a weaker IFN-gamma response to both native and denatured CII that did healthy control individuals (P-).02 and 0.04, respectively). Stimulation with the standard recall antigens PPD and killed influenza virus yielded a median stimulation index with PPD of 10.0 for RA patients and 51.3 for healthy control individuals and with influenza of 12.3 for RA patients and 25.7 for healthy, control individuals. The RA patients displayed markedly lower responsiveness to both PPD and killed influenza virus than did healthy control individuals (Fig. 1b). IFN-gamma responses to all antigens were abrogated when coincubating with antibodies blocking MHC class II. The low response to PPD and killed influenza virus in RA patients relative to that of healthy control individuals reflects a general downregulation of antigen-induced responsiveness of T cells from RA patients [6-8]. That no difference between the RA group and the control group was recorded CII-induced IFN-gamma production therefore indicates that there may be an underlying increased responsiveness to CII in RA patients, which is obscured by the general downregulation of T-cell responsiveness in these patients. In order to address this possibility, we calculated the fraction between individual values for the CII-induced IFN-gamma production and the PPD-induced and killed influenza virus-induced IFN-gamma production and the PPD-induced and killed influenza virus-induced IFN-gamma production, and compared these fractions. A highly significant difference between the RA and health control groups was apparent after stimulation with both native CII and denatured CII when expressing the response as a fraction of that with PPD (Fig. 2a). Similar data were obtained using killed influenza virus-stimulated IFN gamma values as the denominator (Fig. 2b).When comparing the compensated IFN gamma response to denatured CII stimulation between RA patients with different HLA genotypes, highly significant differences were evident, with HLA-DRB1*0401 patients having greater CII responsiveness than patients who lacked this genotype (Fig. 3a). HLA-DQ8 positive patients also displayed a high responsiveness to CII as compared with HLA-DQ8 negative RA patients (Fig. 3b). These associations between the relative T-cell reactivity to denatured CII and HLA class II genotypes were not seen in healthy control individuals. Similar results were achieved using influenza as denominator (P = 0.02 for HLA-DRB1*0401 and P = 0.01 for HLA-DQ8). DISCUSSION: No reports have previously systematically taken the general T-cell hyporesponsiveness in RA into account when investigating specific T-cell responses in this disease. In order to address this issue we used the T cell responses to PPD and killed influenza virus as reference antigens. This was made on the assumption that exposure to these antigens is similar in age-matched and sex-matched groups of RA patients and healthy control individuals. The concept of a general hyporesponsiveness in RA T cells has been documented in several previous reports, in which both nominal antigens [6,7,8] and mitogens [11,12,13] have been used. The fact that a similar functional downregulation in RA PBMCs was obtained with both PPD and killed influenza virus as reference antigens strengthens the validity of our approach. We identified an association between the IFN-gamma response to CII and HLA-DRB1*0401 and HLA-DQ8 in the RA patient group, which is of obvious interest because both these MHC class II alleles have been associated with high responsiveness to CII in transgenic mice that express these human MHC class II molecules [14,15]. There was no association between high anti-CII levels and shared epitope (HLA-DRB1*0401 or HLA-DRB1*0404). CONCLUSION: CII, a major autoantigen candidate in RA, can elicit an IFN-gamma response in vitro that is associated with HLA-DRB1*0401 and HLA-DQ8 in RA patients. This study, with a partly new methodological approach to a classical problem in RA, has provided some additional support to the notion that CII may be a target autoantigen of importance for a substantial group of RA patients. Continued efforts to identify mechanisms behind the general hyporesponsiveness to antigens in RA, as well as the mechanisms behind the potential partial anergy to CII, may provide us with better opportunities to study the specificity and pathophysiological relevance of anti-CII reactivity in RA. PMID- 11219395 TI - Re: Orthodontic treatment with fixed appliances in the General Dental Service in Scotland. PMID- 11219396 TI - Web alert. PMID- 11219397 TI - Web alert. PMID- 11219399 TI - Web alert. Rheumatology. PMID- 11219398 TI - Web alert. PMID- 11219400 TI - [Prevention using new media. Well packaged half-thruths are counterproductive]. PMID- 11219401 TI - [2 platelet inhibitors administered at the same time. Improved prognosis in myocardial infarct?]]. PMID- 11219403 TI - [Use of the Appropriateness Evaluation Protocol in inpatient ENT practice]. AB - BACKGROUND AND OBJECTIVE: Determination of inappropriate hospital use is of increasing importance due to limited resources in health care. The Appropriateness Evaluation Protocol (AEP) serves as an instrument to identify this inappropriate hospital use. It was designed in the USA in 1981 for use in Internal Medicine and General Surgery and consists of criteria items to assess the appropriateness of hospital admissions and days of care. PATIENTS/METHODS: The present study aims to examine the practicability of the AEP in Otorhinolaryngology. The charts of all patients hospitalized in the ENT Department at that particular day were surveyed on 4 consecutive Wednesdays. Three reviewers each reviewed 196 charts. RESULTS: The overall level of inappropriate use was 41.5%. Presuming that the day preoperative to elective surgery was appropriate, the level was 23.1%. CONCLUSIONS: The critical comparison between this result and the actual reasons for hospital admissions and days of care showed, that the present German version of the AEP is less suitable for use in Otorhinolaryngology. Based on the experiences with the AEP an AEP adjusted to Otorhinolaryngology (AEP-ENT) is proposed. PMID- 11219402 TI - H3 receptor-mediated inhibition of intestinal acetylcholine release: pharmacological characterization of signal transduction pathways. AB - The present study investigates the mechanisms through which prejunctional histamine H3 receptors modulate intestinal cholinergic neurotransmission. The experiments were performed on longitudinal muscle-myenteric plexus preparations of guinea pig ileum, preincubated with [3H]choline, superfused with physiological salt solution containing hemicholinium-3, and subjected to electrical field stimulation. The stimulation-induced outflow of radioactivity was taken as an index of endogenous acetylcholine release. The electrically induced [3H]acetylcholine release was inhibited by histamine (EC50)=33.5 nM) or the H3 receptor agonist R-alpha-methylhistamine (EC50=41.6 nM), whereas it was not affected by pyridylethylamine (H1 agonist), impromidine (H2 agonist), pyrilamine (H1 antagonist), cimetidine (H2 antagonist), thioperamide or clobenpropit (H3 antagonists). The inhibitory effects of histamine or R-alpha-methylhistamine were antagonized by thioperamide (pKd= 8.31 and 8.53, respectively) or clobenpropit (pKd=9.44 and 9.32, respectively), but not by pyrilamine or cimetidine. The modulatory action of histamine on the evoked tritium outflow was attenuated by pertussis toxin and abolished by N-ethylmaleimide, two selective blockers of Gi/Go proteins. Tetraethylammonium or 4-aminopyridine, acting as inhibitors of voltage-dependent K+ channels, enhanced the evoked tritium outflow when tested alone, and apparently counteracted the inhibitory effect of histamine. However, the blocking actions of tetraethylammonium and 4-aminopyridine were no longer evident when their enhancing actions were compensated by appropriate reductions of Ca2+ concentration in the superfusion medium. Histamine-induced inhibition of evoked tritium output was enhanced by omega-conotoxin, a selective blocker of N type Ca2+ channels, or low Ca2+ concentration, whereas it was not modified by nifedipine, an antagonist of L-type Ca2+ channels. In addition, the inhibitory effect of histamine was not significantly affected by forskolin (activator of adenylyl cyclase), 8-bromo-cyclic AMP (a stable analog of cyclic AMP), rolipram (a selective blocker of type IV phosphodiesterase), phorbol myristate acetate (activator of protein kinase C), H-89 (N-(2-[p-bromocinnamylamino]ethyl)-5 isoquinolinesulfonamide, inhibitor of protein kinase A), Ro-31-8220 (2-(1-[3 (amidinothio)propyl]-1H-indol-3-yl)-3-(1-methylindol-3-yl)-maleimide, inhibitor of protein kinase C), KT5823 (N-methyl-(8R*,9S*,11S*)-(-)-9-methoxy-9 methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H,11H-2,7b,11a triazadibenzo [a,g]cycloocta[c,d,e]-trinden-1-one, inhibitor of protein kinase G), or lavendustin A (inhibitor of tyrosine kinase). The present results indicate that histamine inhibits intestinal cholinergic neurotransmission through presynaptic H3 receptors coupled to Gi/Go proteins. It is suggested that adenylyl cyclase, serine-threonine protein kinase and tyrosine kinase pathways are not implicated in this regulatory action, and that Gi/Go proteins modulate the activity of N-type Ca2+ channels through a direct link, thus causing a reduced availability of extracellular Ca2+ at the level of ileal cholinergic nerve terminals. PMID- 11219404 TI - [2000 Nobel Prize in Medicine. Communicating nerve cells]. PMID- 11219405 TI - [Orbital space-occupying lesions. Practical aspects of imaging]. AB - During the period 1992-1998,we diagnosed orbital tumors in 23 cases at the MLU Halle-Wittenberg. In the intraconal compartment we mostly saw cavernous hemangiomas and neurogenic tumors. Lymphomas and a primary meningioma were located in the extraconal space. Beneath the periosteum, bony processes, tumors of the sinuses, dermoid-and epidermoid-cysts normally occur, but we only observed metastases and hematomas. Furthermore,tumors of the lacrimal gland and inflammatory lesions were diagnosed. Orbital tumors are uncommon lesions, whose location in the orbit gives an important hint to differential diagnosis, because a high percentage of various pathologies is located in special compartments of the orbit. According to our results,the MRI-scan is usually sufficient for differentiation and for preoperative planning in order to reduce the X-ray dose of the lens. CT-scans with contrast are sometimes necessary for examining bone destroying processes and for planning the surgical approach to removing the tumor. X-rays of the skull widely lost their importance in the exact diagnostic of orbital tumors. B-scan ultrasonic imaging is reserved for screening and follow up examination. Despite the use of MRI and CT scanning, the histological examination remains necessary. PMID- 11219406 TI - [Neurofeedback in therapy of tinnitus]. AB - BACKGROUND AND OBJECTIVE: Biofeedback is known as a possibility to control physiologic processes like body temperature or heart frequency. Neurofeedback is a form of biofeedback linked to aspects of the electrical activity of the brain such as frequency, location or amplitude of specific EEG activity. It has been successfully used in patients with closed head injury, hyperactivity disorder or epilepsy. PATIENTS/METHODS: In this study 40 patients with tinnitus were treated with neurofeedback.They trained to upregulate the amplitude of their alpha activity and downregulate the amplitude of beta-activity during muscle relaxation and acoustic orientation on sounds or music in order to suppress their tinnitus. RESULTS: After 15 sessions of training 24 patients with a duration of their tinnitus for an average of 1 year showed significant increase of alpha-amplitudes while 16 patients with duration of their tinnitus on an average of 7 years showed a decrease of beta-amplitudes without any change in alpha-activity. After the training all patients had a significant reduction of the score in the tin nitusquestionaire of Gobel and Hiller. In a control-group of 15 persons without tinnitus we didn't see any changes of alpha- or beta-amplitudes during the same training. CONCLUSIONS: In conclusion neurofeedback is a new therapy for patients with tinnitus. Patients get the possibility of selfcontrol and therefore of influence on their disease. PMID- 11219407 TI - [Warming inhaled air in the nose]. AB - BACKGROUND AND OBJECTIVE: The purpose of this study was to determine whether the temperature at the end of inspiration is the same as the temperature a few seconds after breathing stops at the end of inspiration to study if the nasal mucosa are capable of providing heat during a cessation of breathing. PATIENTS/METHODS: Fifteen healthy volunteers were included in the study. The temperature at the end of inspiration was compared to the temperature obtained 5 s after cessation of breathing at the end of inspiration and at the end of expiration. Intranasal temperature measurements were taken at three locations in the nose with a miniaturized thermocouple. RESULTS: The temperature increased during cessation of breathing at all locations. The highest temperature differences between the end of inspiration and 5 s later (breathing at rest) could be observed at the nasal valve area. The lowest temperature difference was found in the nasopharynx. At the end of expiration,the temperature decreased only slightly from the nasopharynx to the nasal valve area. CONCLUSIONS: The anterior part of the nose in particular is capable of heating the inspired air. This is also important for humidification. Heating of inspired air requires special anatomical conditions of the anterior nasal segment. PMID- 11219408 TI - [Prevention of endocarditis within the scope of ENT interventions. Current recommendations]. PMID- 11219410 TI - [Voice change and laryngeal obstruction caused by a median thyroglossal duct cyst]. AB - Thyroglossal duct cysts are common primary neck tumors, resulting from remnants of the ductus thyroglossus. They can occur at any point along the migratory path of the thyroid gland anlage until the 2nd or 3rd decade of life. The usual symptoms leading to the diagnosis are painless midline neck masses orfistulas. Despite their close proximity, the cysts normally do not affect the larynx. We report on the eighth case mentioned in the world literature of a thyroglossal duct cyst invading the larynx in a 62-year-old patient. Preoperatively, the voice of the patient sounded metallic, and the frequency of the voice field was reduced. Postoperatively, the voice onset was physiological, and the voice increased by an octave in the higher frequencies. The intonation of the voice was steady. The analysis of formants of the vowels "a" and "i" showed that the fourth formant of the vowel "i" was lower in frequency postoperatively. PMID- 11219409 TI - [Clinical aspects of tracheopathia osteoplastica]. AB - Tracheopathia osteoplastica is a rare condition of the tracheobronchial tree characterized by the formation of multiple osseous or cartilaginous submucosal nodules which protrude into the lumen. Clinical features, pathological anatomical, and radiological findings are described and discussed on the basis of three recent cases and a literature review.Two female patients (age 56 and 62 years) and one male (age 44 years) presented with recurrent tracheobronchitis, a "difficult intubation" at the time of an emergency situation requiring tracheostomy. The diagnosis was confirmed by tracheoscopy. CT scans showed radiodense nodular thickening of the tracheal wall compromising the lumen in all patients, whereas plain chest radiography revealed scalloped linear calcification in only one case. Histologically the nodules consisted of lamellar-type bone covered by normal mucosa. None of the patients needed therapeutic measures as there was no impairment of ventilatory function. The long-term observations (>15 years) of a few authors suggest that the disease is of benign course and does not deteriorate. PMID- 11219411 TI - [Degenerative changes in parapharyngeal schwannoma "ancient schwannoma". Case report and review of the literature]. AB - Schwannomas are rare, slow-growing, benign neoplasms derived from the schwann cells of the nerve sheath of peripheral nerves. Extracranial schwannomas are most frequently localized within the extremities or the head and neck region. For example, they are common in the skull base, the carotid sheath, and the parapharyngeal space. Beneath several histological variants, schwannomas showing prominent degenerative changes (so-called,,ancient schwannomas") are exceedingly rare. Histopathological features, such as degenerative changes and nuclear atypias in ancient schwannomas, may be easily confused with malignant mesenchymal neoplasm.We present the case of a 32-year-old female who required surgery for a parapharyngeal neoplasm. Histological examination revealed features of an ancient schwannoma. PMID- 11219412 TI - [Radiation-induced malignant fibrous histocytoma of the oropharynx]. AB - Malignant fibrous histiocytoma is a rare sarcoma. This is the report of a radiation-induced histiocytoma of the right tonsillar region. Because of squamous cell carcinoma of the left tonsil, a 64-year-old woman was treated with primary surgery and postoperative radiotherapy. Six years later, a histiocytoma was diagnosed histologically within the former field of radiation. This second primary tumor was resected radically. Clinical, radiological, and histological findings are presented, and the importance of this very rare malignant tumor, especially when it is radiation-induced, is discussed. PMID- 11219413 TI - [Current aspects on diagnosis of sleep-related breathing disorders]. AB - Various diagnostic procedures are available to diagnose sleep-related breathing disorders. The present review examines the amount of diagnostics necessary for daily routine. Concerning taking patients' history, the medical examination and nasal parameters, no new recommendations derive from this review. On the other hand,the detection of the site of pharyngeal obstruction seems to have become less important than it was a couple of years ago.Today, the upper airway is considered to be a complex, functional unit. The classification of the obstruction site into retropalatal and retrolingual seems to be oversimplified. A fully attended, complete polysomnography in the sleep laboratory no longer seems to be necessary in every case of suspected sleep-related breathing disorders. Under certain conditions, ambulatory recording units provide cost-effective alternatives. PMID- 11219414 TI - [Communication and personality. Markers for successful leadership]. PMID- 11219415 TI - [Acute healing loss with subsequent cranial nerve paralysis. Wegener granulomatosis]. PMID- 11219416 TI - [Digital photo- and video-documentation. 2]. PMID- 11219417 TI - Quality of life for long-term survivors of cancer: influencing variables. AB - The study's purpose was to describe the relations among self-esteem, learned resourcefulness, and social support, and to show how they predict health-related quality of life (HRQL) for long-term survivors of cancer. With advances in oncology and increased survival, variables influencing the HRQL of long-term survivors of cancer must be explored. The design was descriptive and correlational. Five instruments were sent to 456 long-term survivors in southern California. Data were analyzed for 62 of 111 consenting individuals, most of whom were married, retired, white, college-educated, female survivors of breast cancer older than 60 years of age treated by radiation and surgery. Subjects with higher self-esteem reported higher HRQL (r = 0.69; p = 0.00). Learned resourcefulness had a significant negative relation with HRQL (r = -0.32; p = 0.01). Social support was operationalized as functional components, network properties, and recent loss. Only the loss component of social support had a significant negative relation with HRQL (r = -0.38; p = 0.00). Together, the three variables explained more than half of the variance (R2 = 0.53) of HRQL, with self-esteem being the strongest predictor. The HRQL of long-term survivors of cancer may increase with interventions such as both survivor- and nurse-led support groups aimed at supporting and improving self-esteem. In addition, education to anticipate social support losses may further enhance HRQL. PMID- 11219418 TI - Predictors of quality of life in rural patients with cancer. AB - Quality of life (QOL) as an outcome for cancer treatment has been studied primarily in urban populations. Yet, descriptions of rural dwellers suggest that their perception of QOL may differ from that of their urban counterparts. The purpose of this study was to examine QOL in people with a cancer diagnosis of at least 1 month duration in two similar rural northeastern states. The Functional Assessment of Cancer Therapy General (FACT G) scale was completed by 344 respondents. The mean QOL score was 89.41 +/- 16.55. State of residence, gender, known recurrence, and marital status were significant predictors of QOL, explaining 18.3% of the variance in this study. Age, education level, income, type of cancer, living arrangements, and time since diagnosis were not predictive. The QOL scores in this rural sample were higher than those reported earlier for predominantly urban dwellers. Future research is needed to understand these differences. PMID- 11219419 TI - Hospice nursing: the specialty. AB - The purpose of this study was to identify and delineate what experienced hospice nurses perceive as the knowledge and skills base essential to their practice of hospice nursing as a specialty. Little of this specialty is taught in basic nursing programs, so another purpose was to determine the methods hospice nurses use for knowledge and skills acquisition. The qualitative study method of focused ethnography was used. This method allowed the researcher to examine hospice nurses in the context of their own community-based agency, enter the research arena with specific questions, describe the topic from the viewpoint of the participants, use multiple data sources, and begin data analysis concurrently with data collection, which continued until saturation was reached. During data analysis, 11 categories emerged. Four of these categories involved skills: (a) assessment skills, (b) communication skills, (c) technical skills, and (d) management skills; and seven categories primarily involved knowledge: (a) end stage disease process, (b) signs of impending death, (c) palliative therapeutics, (d) collaboration between disciplines, (e) advocacy, (f) philosophy and ethics of hospice care, and (g) family dynamics. Of these 11 categories, the one discussed and observed most often was that of assessment skills. It was found that the hospice nurses learned their specialty by doing it. However, the need for graduate education in hospice nursing became apparent. PMID- 11219420 TI - Caregivers' descriptions of patients with advanced breast cancer in connection with supervision sessions in a surgical ward. AB - The purpose of this study was to describe the content of caregivers' (health care professionals') presentation of care situations as told at supervision sessions. For 1 year, 21 caregivers in a surgical ward of a county hospital in the middle of Sweden participated in a clinical supervision session 2 hours every third week. The participants in the supervision sessions were divided so as to form three mixed groups composed of registered nurses, practical nurses, physiotherapists, and physicians. The purpose of the supervision sessions was to give caregivers the opportunity to reflect on different care situations in a way that contributed to the development of patient care. The 38 supervision sessions were tape-recorded and transcribed verbatim. The transcripts were analyzed using a qualitative content analysis. The caregivers described difficult care situations focusing on the feelings of patients, relatives, and caregivers, with an emphasis on the caregivers' being dominant. Difficult care situations were described as giving caregivers feelings of discomfort, powerlessness, and reduced self-esteem. These feelings were described as arising in connection with caring for women with advanced breast cancer and other seriously ill patients in an organization lacking clear goals and rules. This study found that supervision sessions offering an opportunity to reflect on the difficult care situations are important for caregivers. These sessions seem therefore to be of vital importance for the future development of cancer care on the surgical ward. PMID- 11219421 TI - African American women and breast cancer: notes from a study of narrative. AB - Survival after breast cancer and after all cancers is significantly worse for African American women than for others. Although many reasons have been proposed, no studies have explored the reception of messages about breast cancer by African American survivors of this disease, and how public images and discourses about breast cancer affects both their perceived risk for this disease and their experiences of illness. Narrative accounts of their lived experiences with breast cancer were collected from 23 African American survivors of breast cancer. Three themes have emerged: (a) Breast cancer is perceived to be a white woman's disease; (b) cancer is caused by experiences of repeated traumatic heartbreak; and finally, (c) there is a perceived lack of social support and understanding for the unique life experiences of the African American survivor of breast cancer. Nurses are on the front line of patient care. In the context of the managed care environment, they spend more time with patients than other health care providers and are soundboards for many patient concerns. As such, they can use the information provided in this study to inform high-risk women, current patients, partners, and other individuals in the medical community of how African American women might inaccurately access their personal risks for breast cancer, despite the public emphasis on this disease. Through the use of culturally sensitive pamphlets, nurses and other medical practitioners can also open discussions with underserved and minority patients as a means of realistically addressing some of these women's fears about breast cancer. These fears are barriers to effective cancer prevention because these individuals may consciously or unconsciously link a diagnosis of breast cancer, or even behaviors related to cancer prevention, to a potential death sentence. PMID- 11219422 TI - The Breast Cancer Distance Education Program: development and evaluation of a course for specialist breast care nurses. AB - The Breast Cancer Distance Education Program is the first tertiary-based education program for specialist breast care nurses in Australia. The program covers current treatment options, psychosocial issues, and professional development issues relating to breast cancer nursing. For the first two student intakes (n = 53), precourse, postcourse, and 3-month follow-up surveys were conducted to assess the perceived value of the course, identify any limitations, and note changes in practice that arose. Before taking the course, most of the students had experience in breast cancer nursing, but lacked confidence and hoped to learn more about responding effectively to psychosocial issues through communication, counseling, and provision of support to patients and their carers. After taking the course, the students were very positive about the course content, resources, and teaching support. They reported learning new skills for addressing psychosocial issues and symptom management arising from a diagnosis of breast cancer, stating a desire to implement these new skills. Comparison between results from the three surveys indicated that students' confidence in providing breast cancer support increased significantly in most areas of practice, and was maintained at 3-month follow-up survey. Results suggest that students met the course objectives successfully, and in most cases subsequently translated their knowledge into improved practice. PMID- 11219423 TI - Relationship issues of women with breast cancer. AB - This in-depth, qualitative pilot study explored the impact of breast cancer on specific dimensions of the relationships and roles of women. It included interaction within the partner relationship as well as with family, friends, and colleagues. Data were obtained by individual and group interviews from 10 women with a diagnosis of breast cancer and 5 male partners. Both partnered and single women participated. There were four major findings seldom discussed in the literature, which have important implications for preventive intervention. First, partner relationships troubled before the diagnosis as well as those characterized by mutual caring faced challenges and negative changes. Second, in an effort to protect each other, communication within the partner dyad became less open, and there were changes in the usual manner of conflict resolution. Third, unpartnered women appeared to be more vulnerable to problems of negative adjustment, largely because of relationship issues. Fourth, participants confirmed the need for a comprehensive intervention to facilitate coping with issues relative to relationships, intimacy, and sexuality. Although the sample was small, in-depth data were obtained that provide a basis for specific areas in which further empirical investigation is needed, and they indicate that preventive intervention may well be warranted. PMID- 11219424 TI - The needs of children and adolescents with cancer for information and social support. AB - Research has indicated that information and social support may have helped children and adolescents with cancer to cope with their illness and lead normal lives. However, recent researchers have reported that youths with cancer express a clear interest in receiving more information and social support. This study reviewed research on information and social support for children and adolescents with cancer to understand their needs. Young patients with cancer showed high uncertainty about cancer. Besides, adolescents with cancer were more in conflict with their parents than healthy youths. Discussions on future plans or death are difficult for young people with cancer. They also are frequently absent from school over time. Moreover, they want to make healthy friends. To fulfill the needs of these youths, nurses should be aware not only of individualized information and social support, but also of these factors from an ecologic perspective. Further qualitative research is required to identify the needs of youths with cancer and resolve these issues. PMID- 11219425 TI - Chinese women's experiences and images of the Pap smear examination. AB - Cervical cancer remains a significant cause of mortality and morbidity in Chinese women, despite the efficacy of the screening procedure for the disease. This article focuses on specific gender and culturally related experiences of Chinese women presenting for Papancolaou (Pap) tests. The first phase of a descriptive exploratory study involved the administration of a questionnaire to a total population of female Hong Kong Chinese clerical and technical staff working in academic departments of a tertiary institution. The second phase consisted of in depth semistructured interviews with a purposive sample of women to explore experiences of Pap smear screening. Of these women, 68.2% associated pain with a Pap smear. In addition, 78.6% of the women associated a Pap smear with embarrassment. Older women were more likely to experience pain and embarrassment during the procedure. In the qualitative data, women's personal images and experiences reflected four subthemes including pain, sexual connotations of the procedure, vulnerability, and diminished embarrassment after childbirth. The second substantive theme, characteristics of the practitioner, highlighted the importance of procedural, interpersonal, and culturally sensitive skills, particularly in respect to information-giving and interaction with women. The conclusion outlines the nursing implications for Chinese women presenting for Pap smears in terms of cultural sensitivity as a means of enhancing attendance patterns. PMID- 11219427 TI - Correlations between theoretical and experimental determination of heat of formation of certain aromatic nitro compounds. AB - Heats of formation of energetic materials can be obtained either experimentally or theoretically. In order to compare the results of the two methods, some correlation methods were proposed in this study. The molecular structures and heats of formation of nitrobenzenes, nitrotoluenes, nitroanilines, and nitrophenols were calculated by Dewar's AMI and Stewart's PM3 methods. Correlations of heats of formation between the theoretical calculations and experimental results were evaluated by using the multivariable linear regression method. Results indicate that there are very precise correlations. Based on these correlations, heats of formation of some aromatic nitro compounds can be predicted at 95% predictive interval without experimental analysis. PMID- 11219428 TI - Prediction of programmed-temperature retention values of naphthas by wavelet neural networks. AB - The wavelet neural network (WNN) was used to predict the programmed-temperature retention values of naphthas. In WNN, a Morlet mother wavelet was used as a transfer function, and the convergence speed was faster than other neural networks. Sixty-four compounds (selected randomly from 94) were used as a training set, and the 30 remaining compounds were used as a test set. A very satisfactory result was obtained only after about 8000 training epochs. The other two methods, the artificial neural network (ANN) and the Simpson integral method, were also used for this study. The comparison of results obtained from three methods showed that the WNN is the most suitable tool in predicting programmed temperature retention values of naphthas, consequently this method can be used to provide reliable data for the petrochemical industry. PMID- 11219429 TI - Evaluation of Spartan semi-empirical molecular modeling software for calculations of molecules on surfaces: CO adsorption on Ni(111). AB - This paper reports the use of the PM3(tm) semi-empirical method in the Spartan molecular modeling software to optimize geometries and calculate vibrational frequencies for increasingly complex transition metal- and carbon monoxide (CO) containing systems, culminating in calculations of CO adsorbed on a Ni(111) surface. Mononuclear and dinuclear transition metal carbonyl molecular species were used to establish the level of accuracy that could be expected for vibrational frequencies to provide a context for the results from the adsorbed molecule calculations. One to four CO molecules adsorbed on the (111) face of a 22-atom-nickel crystal were then modeled, and the accuracy of the adsorption geometry and vibrational frequency was evaluated. The calculated CO stretching vibrational frequencies were within 8% larger than the gas phase experimental values for the molecular species and were approximately 10% larger than the range of experimental values for CO on the nickel surface. The geometry optimization predicted that the CO molecules on the Ni(111) surface occupy three-fold hollow sites with no preference for sites over Ni atoms, in agreement with recent structural data and other theoretical calculations. The software was less successful in calculating the CO bond angle to the surface and the distance of the CO molecules from the surface, but the calculation did produce a reasonable distance between CO molecules on the surface. In general, the PM3(tm) method in Spartan shows promise for predicting adsorption sites and vibrational frequencies of molecules on metal surfaces. PMID- 11219430 TI - Stepwise assembling of polypeptide chain energy distributions. AB - The principles and application of conformational analysis software that makes use of a new algorithm are described. It is known that the existence of a local energy minimum in the energy landscape is in general related to the clustering of polypeptide chain conformations near that energy value or, in other words, to a high density of states. A criterion based on this principle is part of an algorithm employed to select subsets of polypeptide chain conformations in broad energy ranges. Chain fragments belonging to these subsets are then combined to build larger polypeptide chains and the corresponding energy distributions. The functionality of the various operations employed in the process is described and the FORTRAN 77 source code that defines the algorithm is listed. The methodology is illustrated with a calculation involving three chain fragments belonging to the cellular prion protein (PrP(C)). PMID- 11219431 TI - Visualization methods in analysis of detailed chemical kinetics modelling. AB - Sensitivity analysis, principal component analysis of the sensitivity matrix, and rate-of-production analysis are useful tools in interpreting detailed chemical kinetics calculations. This paper deals with the practical use and communication of the sensitivity analysis and the related methods are discussed. Some limitations of sensitivity analysis, originating from the mathematical concept (e.g. first-order or brute force methods) or from the software-specific implementation of the method, are discussed. As supplementary tools to the current methods, three novel visual tools for analysis of detailed chemical kinetics mechanisms are introduced: (a) scaled sensitivity analysis which is especially suited for studying initiation reactions where the span of reaction rates is high; (b) automated generation of reaction pathway plots which provides an immediate graphical illustration of the chemical processes occurring; (c) explorative (or chemometric) analysis of accumulated rate of progress matrices which assist in the identification of reaction subsets. The application of these tools are demonstrated by analysing NOx enhanced oxidation of methane at 700-1200 K. PMID- 11219426 TI - Screening the molecular surface of human anticoagulant protein C: a search for interaction sites. AB - Protein C (PC), a 62 kDa multi-modular zymogen, is activated to an anticoagulant serine protease (activated PC or APC) by thrombin bound to thrombomodulin on the surface of endothelial cells. PC/APC interacts with many proteins and the characterisation of these interactions is not trivial. However, molecular modelling methods help to study these complex biological processes and provide basis for rational experimental design and interpretation of the results. PC/APC consists of a Gla domain followed by two EGF modules and a serine protease domain. In this report, we present two structural models for full-length APC and two equivalent models for full-length PC, based on the X-ray structures of Gla domainless APC and of known serine protease zymogens. The overall elongated shape of the models is further cross-validated using size exclusion chromatography which allows evaluation of the Stokes radius (rs for PC = 33.15 A; rs for APC = 34.19 A), frictional ratio and axial ratio. We then propose potential binding sites at the surface of PC/APC using surface hydrophobicity as a determinant of the preferred sites of intermolecular recognition. Most of the predicted binding sites are consistent with previously reported experimental data, while some clusters highlight new regions that should be involved in protein-protein interactions. PMID- 11219432 TI - A QSPR model for the prediction of the gas-phase free energies of activation of rotation around the N-C(O) bond. AB - A novel approach to predict the gas-phase rotational activation energies of amides is presented. The quantitative structure property relationship (QSPR) treatment, using the statistical package, comprehensive descriptors for structural and statistical analysis (CODESSA), resulted in a three-parameter equation with R2 = 0.982 for the deltaG(double dagger)gas, of a set of 24 N,N dialkylamides. PMID- 11219433 TI - Implementation of similarity model in the CSB system for chemical reaction predictions. AB - A new algorithm for predicting the course of chemical reactions, implemented in the CSB system is presented. It allows to use of four various models for reaction generation, that lead to create different solution space according to the needs of the user. Depending on the chosen model one can expect solutions featuring great completeness or great reliability. PMID- 11219434 TI - ChromWin--a computer program for the determination of enantiomerization barriers in dynamic chromatography. AB - The software program ChromWin simulates interconversion profiles in dynamic chromatography (rearrangements, isomerizations, epimerizations, diastereomerizations and, notably, enanatiomerizations) on a personal computer in a user-friendly environment. ChromWin is especially suited for systems involving large plate numbers, e.g. gas chromatography (GC) and capillary electrophoresis (CE, CEC, MEKC), and first or pseudo-first order reactions. ChromWin (1) simulates the elution profiles of interconverting enantiomers by different models and yields the rate constant, (2) allows automation of the 'find enantiomerization barrier' function, (3) helps to optimise separation parameters by visualization of the separation process and (4) provides other useful tools for chromatography. In addition to the theoretical plate and the stochastic model a modified and improved stochastic model has been developed and implemented in the program. PMID- 11219435 TI - QSPR studies of PCBs by the combination of genetic algorithms and PLS analysis. AB - A hybrid approach that combines genetic algorithms (GA) with PLS analysis is proposed, and a modified cross-validation correlation coefficient (MCVR2) is used as fitness function. The method is applied to QSPR studies of PCBs, in comparison with class regression, and many better models are obtained for each property studied. By MCVR2, not only can the low dimensional PLS models be obtained, but also the best multiple least squares regression (MLS) models. Moreover, the results show the WHIM descriptors that contain information about the whole 3D molecular structure are excellent descriptors for molecular modeling, but by adding some common molecular parameters representing total molecular properties the quality of the models is still improved slightly. PMID- 11219436 TI - High order spatial discretisations in electrochemical digital simulation. 2. Combination with the extrapolation algorithm. AB - The application of fourth order discretisations of the second derivative of concentration with respect to distance from the electrode, in electrochemical digital simulations, is examined. In the bulk of the diffusion space, a central five-point scheme is used, and six-point asymmetric schemes are used at the edges. In this paper, the scheme is applied to the extrapolation technique, based on the backward implicit (BI) algorithm for temporal integration, which (with extrapolation) allows higher orders in time as well. The method is found to be stable, using both the von Neumann and matrix methods. Exceptional efficiency is obtained both for Cottrell and chronopotentiometry simulations, requiring as few as 3-5 steps in time, starting at the dimensionless time t = 0 to gain four decimal accuracy at t = 1. PMID- 11219437 TI - Individually measured feed intake characteristics and growth performance of group housed weanling pigs: effects of sex, initial body weight, and body weight distribution within groups. AB - Feed intake characteristics of 192, 27-d-old weanling pigs housed in groups and given ad libitum access to feed and water were measured individually with the use of computerized feeding stations. The groups were either homogeneous or heterogeneous as to BW distribution; pigs of three defined initial BW classes were used (mean BW of 6.7, 7.9, or 9.3 kg). The effects of BW distribution, BW class, and sex were studied with regard to average performance traits, latency time (interval between weaning and first feed intake), initial feed intake (intake during the first 24 h following first feed intake), and daily increase in feed intake during the interval between first feed intake and the day on which energy intake met or exceeded 1.5 times the maintenance requirement. Homogeneous and heterogeneous groups had similar latency times, initial feed intakes, and daily increases in feed intake. For the period 0 to 34 d after weaning, ADFI and ADG were also similar for homogeneous and heterogeneous groups, but gain:feed ratio was greater (P < 0.05) in the homogeneous groups. Gilts had higher (P < 0.05) initial feed intakes than barrows and also had greater (P < 0.05) ADFI and ADG during the period 0 to 13 d after weaning. Pigs with average BW of 6.7 kg had higher (P < 0.05) initial feed intakes than their counterparts with average BW of 7.9 kg and 9.3 kg, but the daily increase in feed intake was similar for the three groups. The lighter pigs had more daily visits and a lower feed intake per visit and tended to have a shorter postweaning latency to the onset of feeding than the heavier pigs. This study indicates that the high variability in early feeding behavior among group-housed weanling pigs may be related to BW and sex. PMID- 11219438 TI - Effectiveness of GnRH plus prostaglandin F2alpha for estrus synchronization in cattle of Bos indicus breeding. AB - Postpartum and lactating crossbred cows containing a percentage of Bos indicus breeding at three locations were studied to determine the efficacy of GnRH + PGF2alpha combinations for synchronization of estrus and(or) ovulation. Cows were equally distributed to each of three treatments by body condition score at the start of the experiment (d 0). All cows received 100 microg of GnRH on d 0 and 25 mg of PGF2alpha 7 d later. The three insemination protocols included 1) AI 12 h after exhibiting estrus during d 7 to 12 of the experiment (Select-Synch; n = 197); 2) timed-AI + 100 microg of GnRH on d 9 of the experiment (CO-Synch; n = 193); 3) AI 12 h after exhibiting estrus during d 7 to 10 of the experiment. Cows not exhibiting estrus by d 10 were timed-AI and injected with 100 microg of GnRH on d 10 of the experiment (Hybrid-Synch; n = 200). The percentage of cows exhibiting estrus during d 7 to 12 of the experiment was lower (P < 0.05) for CO Synch (17.6%) cows than for Select-Synch or Hybrid-Synch (45.2 and 33.0%, respectively) cows, which did not differ (P > 0.05). For the Select-Synch and Hybrid-Synch cows that exhibited estrus during d 7 to 10 of the experiment and were artificially inseminated, conception rates were similar across treatments (50.5%). Pregnancy rates were greater (P < 0.01) for CO-Synch and Hybrid-Synch (31.0 and 35.5%, respectively) cows than for Select-Synch (20.8%) cows. A greater (P < 0.01) percentage of cycling cows became pregnant (34.5%) than noncycling cows (25.9%) across all treatments. The CO-Synch and Hybrid-Synch synchronization protocols resulted in greater pregnancy rates compared with the Select-Synch protocol in postpartum and lactating crossbred cows containing a percentage of Bos indicus breeding. PMID- 11219439 TI - Interactions in postweaning production of F1 cattle from Hereford, Limousin, or Piedmontese sires. AB - A 2-yr study was conducted to evaluate the interactions of castration, feeding length, and dietary CP on growth and carcass characteristics of male cattle (bulls and steers) that vary in expression of muscular hypertrophy. Crossbred cows were bred by AI to Hereford, Limousin, or Piedmontese bulls, which represented genotypes with normal, moderate, and hypermuscularity, respectively, but with similar mature weights. Male calves (131 in yr 1 and 120 in yr 2) were placed in pens with individual electronic feeding gates. Calves were fed growing diets until they reached 386 kg BW and then were individually switched to finishing diets for 90 or 132 d. Interactions were observed among sire breed, gender, and feeding length on carcass composition. Bulls were more efficient than steers in producing live weight gain. Length of finishing period accounted for a larger source of variation than gender for weight characteristics, whereas gender was the larger source of variation for carcass composition. Concentration or degradability of dietary CP influenced rate of gain from weaning to 386 kg. Interactions resulting from varying management on carcass characteristics among calves of different sire breeds indicate that unique strategies may be beneficial for the production of meat from these breeds. PMID- 11219441 TI - Comparison of threshold vs linear and animal vs sire models for predicting direct and maternal genetic effects on calving difficulty in beef cattle. AB - This study compared the accuracy of several models for obtaining genetic evaluations of calving difficulty. The models were univariate threshold animal (TAM), threshold sire-maternal grandsire (TSM), linear animal (LAM), and linear sire-maternal grandsire (LSM) models and bivariate threshold-linear animal (TLAM), threshold-linear sire-maternal grandsire (TLSM), linear-linear animal (LLAM), and linear-linear sire-maternal grandsire (LLSM) models for calving difficulty and birth weight. Data were obtained from the American Gelbvieh Association and included 84,420 first-parity records of both calving difficulty and birth weight. Calving difficulty scores were distributed as 73.4% in the first category (no assistance), 18.7% in the second, 6.3% in the third, and 1.6% in the fourth. Included in the animal models were fixed sex of calf by age of dam subclasses, random herd-year-season effects, and random animal direct and maternal breeding values. Sire-maternal grandsire models were similar to the animal models, with animal and maternal effects replaced by sire and maternal grandsire effects. Models were compared using a data splitting technique based on the correlation of estimated breeding values from two samples, with one-half of the calving difficulty records discarded randomly in the first sample and the remaining calving difficulty records discarded in the second sample. Reported correlations are averages of 10 replicates. The results obtained using animal models confirmed the slight advantage of TAM over LAM (0.69 vs 0.63) and TLAM over LLAM (0.90 vs 0.86). Bivariate analyses greatly improved the accuracy of genetic prediction of direct effects on calving difficulty relative to univariate analyses. Similar ranking of the models was found for maternal effects, but smaller correlations were obtained for bivariate models. For sire-maternal grandsire models, no differences between sire or maternal grandsire correlations were observed for TLSM compared to LLSM, and small differences were observed between TSM and LSM. The threshold model offered advantages over the linear model in animal models but not in sire-maternal grandsire models. For genetic evaluation of calving difficulty in beef cattle, the threshold-linear animal model seems to be the best choice for predicting both direct and maternal effects. PMID- 11219440 TI - The effects of grazing, liquid supplements, and implants on feedlot performance and carcass traits of Holstein steers. AB - In each of 2 yr, 20 Holstein steers (185+/-7 kg initial BW) were allocated to each of three treatments: pastured for 4.5 mo on grass/legume pastures and then fed 80% corn diets (DM basis) until slaughter; pastured for 4.5 mo on grass/legume pastures with ad libitum access to molasses-based protein supplements and fed 80% corn diets until slaughter; and placed in a feedlot and fed only 80% corn diets until slaughter (FEEDLOT). Half of the steers in each treatment were initially implanted with Revalor-S and not reimplanted. Supplemented steers on pasture had greater (P < 0.05) ADG than unsupplemented steers, and FEEDLOT steers gained faster and were fatter (P < 0.05) after 4.5 mo. Implanted steers had greater (P < 0.05) ADG with no significant treatment x implant status effect. Supplement intake was variable and related to ambient temperature. During the feedlot phase, steers previously on pasture had greater DMI and ADG (P < 0.05) but were not more efficient than FEEDLOT steers. Percentage of USDA Choice carcasses, fat thickness, dressing percentage, yield grade, and final weight were greater (P < 0.05) for FEEDLOT steers than for steers on other treatments. Implanting increased ADG of all steers but did not affect carcass traits, carcass composition, or feedlot performance during the finishing phase. Holstein steers consuming supplemented and unsupplemented pasture before slaughter will be leaner, have lower carcass weights, and have generally lower quality grades than those fed exclusively in a feedlot when slaughtered at similar ages. PMID- 11219442 TI - Genetic correlations for litter weight weaned with growth, prolificacy, and wool traits in Columbia, Polypay, Rambouillet, and Targhee sheep. AB - Total litter weight weaned at 120 d postpartum per ewe lambing is often believed to be a measure of range ewe productivity. Genetic correlations for litter weight weaned at 120 d with prolificacy, growth, and wool traits for Columbia, Polypay, Rambouillet, and Targhee sheep were estimated using REML with animal models. Observations per breed ranged from 5,140 to 7,083 for litter weight weaned, from 5,140 to 7,095 for prolificacy traits, from 7,750 to 9,530 for growth traits, and from 4,603 to 18,443 for wool traits. Heritability estimates for litter weight weaned were low and ranged from 0.02 to 0.11. Fraction of variance due to permanent environmental effects averaged 0.05 and, due to effects of mates, averaged 0.01. Estimates of genetic correlations with litter weight weaned varied from breed to breed. The ranges were as follows: 0.42 to 0.65 with litter size born, 0.80 to 0.99 with litter size weaned, -0.22 to 0.28 with birth weight, 0.07 to 0.23 with average daily gain to weaning, -0.56 to 0.19 with fleece weight, -0.15 to 0.02 with fleece grade, and -0.11 to 0.08 with staple length. Results suggest that, if selection were practiced on litter weight weaned, the average correlated responses would be expected to be favorable or neutral for prolificacy, growth, and wool traits although responses might vary from breed to breed. PMID- 11219443 TI - Associations of heart and adipocyte fatty acid-binding protein gene expression with intramuscular fat content in pigs. AB - Intramuscular fat content is a major determinant of meat quality in pigs. Previously, polymorphisms in the adipocyte and heart fatty acid-binding protein genes, A-FABP and H-FABP, have been significantly associated with genetic variation of intramuscular fat content in a Duroc pig population. Further support for the role of H-FABP but not for A-FABP was found in a Meishan crossbred population. However, the effect of closely linked genes could not be excluded in these analyses. To validate the role of A-FABP and H-FABP in intramuscular fat accretion, 153 pigs of a crossbred genotype were evaluated for the A-FABP and H FABP polymorphisms, mRNA, and protein expression levels of both FABP genes and intramuscular fat content in the longissimus lumborum muscle. For H-FABP, statistical analyses showed significant differences in mRNA but not protein expression levels between H-FABP HaeIII PCR-RFLP genotype classes. Between these genotype classes, significant differences in intramuscular fat content were found within barrows but not in gilts. Moreover, H-FABP mRNA but not protein expression levels were significantly related to intramuscular fat content. For A-FABP genotype classes, no significant differences in mRNA and protein expression levels were found. However, a significant difference in intramuscular fat content was found within barrows but not in gilts. In addition, a significant relationship between A-FABP mRNA but not protein expression levels and intramuscular fat content was found. In conclusion, variation of intramuscular fat content could not be explained by differences in A-FABP and H-FABP mRNA and protein expression levels. However, this may be due to limitations of the assays used and(or) the inappropriateness of the time of sampling. Finally, results suggest that A-FABP and H-FABP expression are translationally rather than transcriptionally regulated. PMID- 11219444 TI - Breed effects on growth performance, carcass characteristics, fatty acid composition, and palatability attributes in finishing steers. AB - Crossbred steers (n = 136) were used to assess breed differences in growth performance, carcass characteristics, fatty acid composition (total lipids and phospholipids), and palatability attributes of longissimus muscle. A multiple regression model was applied to crossbreeding data to estimate genetic differences between Simmental and Red Angus at the same level of backfat finish (10 mm). Simmental spent 71 more (P < 0.001) days on feed to acquire the same degree of backfat thickness as Red Angus, had heavier (P < 0.001) slaughter weights, larger (P = 0.002) longissimus muscle area, and increased (P = 0.023) lean yield. Average daily gain did not differ (P = 0.297) between breeds. Simmental were less (P = 0.012) efficient in converting feed to gain than Red Angus. Generally, there were few breed differences in palatability attributes for longissimus and semitendinosus muscles, with the exception of increased (P < 0.05) beef flavor scores for Simmental beef vs Red Angus beef across both muscles. For total lipids, concentrations of myristoleic acid (14:1), palmitoleic acid (16:1), and vaccenic acid (18:1n-7), along with n-6 to n-3 fatty acid (n-6:n 3) ratio, were greater (P < 0.05) in Simmental than Red Angus. In contrast, concentrations of margaric acid (17:0), eicosapentaenoic acid (20:5n-3), and total n-3 polyunsaturated fatty acids (n-3 PUFA) were greater (P < 0.05) in Red Angus than Simmental. For phospholipids, Simmental had lower (P < 0.05) amounts of 20:5n-3, docosahexaenoic acid (22:6n-3), and n-3 PUFA, with a greater (P = 0.017) n-6:n-3 ratio. Activity of delta9-desaturase enzyme in the conversion of palmitic acid (16:0) to 16:1 was greater (P = 0.001) in total lipids from Simmental as compared with Red Angus. A genetic basis for fatty acid differences is suggested, although the biological and practical significance needs to be demonstrated. PMID- 11219445 TI - Inbreeding and effective population size of Japanese Black cattle. AB - The objective of this research was to estimate the amount of inbreeding and effective population size of the Japanese Black breed using pedigree records from bulls and heifers registered between 1985 and 1997. Inbreeding was quantified by three F-statistics: actual inbreeding, inbreeding expected under random mating, and inbreeding due to population subdivision. During the period of 1985 to 1997, the inbreeding expected under random mating increased from 2.3% to 5.0%, whereas the increase of actual inbreeding was more gradual (from 4.7% to 5.4%). The inbreeding due to population subdivision decreased almost linearly and reached 0.5% in 1997, indicating that genetic subdivision of the Japanese Black cattle population has essentially disappeared. The effective size of the breed was estimated from the increasing rate of inbreeding expected under random mating. In the earlier half of this period (1986 to 1990), the breed maintained an effective size of approximately 30. However, after 1991 the effective size sharply decreased and the harmonic mean between 1993 and 1997 was only 17.2. The main cause of this reduction of the effective size was considered to be the intensive use of a few prominent sires. To increase the effective size, an upper limit in the use of AI semen per sire should be imposed. PMID- 11219446 TI - Enterocyte digestive enzyme activity along the crypt-villus and longitudinal axes in the neonatal pig small intestine. AB - Our objective was to examine the distribution of enterocyte digestive enzyme activity along the crypt-villus and longitudinal axes of the small intestine in formula-fed neonatal pigs between the ages of 14 and 18 d. The distended intestinal sac method was used to isolate 12 sequential fractions (F1 through F12) of epithelial cells. Enterocyte migration rate was measured in the proximal and distal intestine using in vivo bromodeoxyuridine labeling. Specific activities of representative villus cell marker enzymes of alkaline phosphatase, aminopeptidase N, sucrase, and lactase increased 6- to 17-fold from F12 (crypt cells) to F1 (villus cells), whereas the crypt cell marker [3H]thymidine incorporation increased 8- to 18-fold from F1 (villus cells) to F12 (crypt cells). Enterocyte migration rate was similar (3.2 vs 3.0 microm/h), whereas the villus height (547.4 vs 908.5 microm) and enterocyte life span (4.7 vs 10.2 d) were markedly lower (P < 0.05) in the proximal than in the distal segments, respectively. In general, the specific activities of all enzymes were lowest in the crypt fractions (F9 through F12) but increased markedly (ranging from 8- to 17-fold) from F12 to F1. The activity of aminopeptidase N was higher and that of sucrase was lower in the distal than in the proximal segment. The activities of the remaining enzymes were similar in the proximal and the distal segments. Our results suggest that the enterocyte life span in the distal small intestine is approximately twice as long as in the proximal small intestine. However, despite the difference in life span, the patterns of enzyme activities along the crypt villus axis were generally similar in the proximal and the distal regions. PMID- 11219447 TI - Muscle glycogen stores and meat quality as affected by strategic finishing feeding of slaughter pigs. AB - The aim of the present study was to investigate whether muscle glycogen stores in slaughter pigs could be decreased through strategic finishing feeding before slaughter. Moreover, preliminary meat quality traits were measured to see whether such a regulation of muscle glycogen stores affected ultimate pH, color, and tenderness in the meat. The strategic finishing feeding was carried out the last 3 wk prior to slaughter. Seven experimental groups with eight animals per group were fed diets low in digestible carbohydrates. A control group with four animals was fed a traditional grower-finishing diet. The muscle glycogen stores were reduced in longissimus muscle (LM) 11 to 26% at the time of slaughter in pigs that were fed the experimental diets compared with the control group. Meat quality measured as ultimate pH and color on LM muscle in half the pigs 24 h postmortem showed that ultimate pH in LM was not affected by the reduction in glycogen stores in the muscles from pigs fed any of the experimental diets. However, the meat from pigs fed the experimental diets was darker than the meat from pigs that were fed the control diet with two of the experimental diets, resulting in significantly lower L* values. Activities of key enzymes in the glycolytic pathway, glycogen phoshorylase a and b, phosphofructokinase, and the fatty acid oxidative pathway, beta-hydrozyacyl-CoA-dehydrogenase, were not affected by the strategic feeding. In contrast, the activity of the proteolytic enzyme calpain as well as its inhibitor calpastatin was influenced by the strategic feeding. Lower activity of mu-calpain and greater activity of calpastatin in the muscle samples from the strategically fed pigs indicate a lesser muscle protein degradation in the muscles compared with muscles of control animals. The present study showed that the muscle glycogen stores in slaughter pigs can be reduced at the time of slaughter through strategic finishing feeding with diets low in digestible carbohydrate without compromising growth rate. PMID- 11219448 TI - The influence of ultimate pH and intramuscular fat content on pork tenderness and tenderization. AB - Intramuscular fat (IMF) and ultimate pH (pHu) influence tenderness, but their roles have not been conclusively determined. Length of storage also affects tenderness and may interact with IMF and pHu. We evaluated the effects of pHu, IMF, and storage time on the tenderness of pork longissimus muscle and determined whether the contribution of the various factors was dependent on genetic line. To obtain variation in IMF, Berkshire (B), Duroc (D) and Hampshire (H) boars were crossed with Yorkshire-Landrace sows. In four trials, a total of 176 pigs were used. To obtain a range in pHu, half of the pigs were deprived of feed before slaughter. Warner-Bratzler shear force (WBS) of each loin was assessed after 2, 7, and 14 d of storage at 0 to 2 degrees C. Warner-Bratzler shear force decreased (P < 0.05) from 4.89 kg at d 2 to 4.16 kg at d 7 to 3.52 kg at d 14. The H pork (n = 62) had a lower (P < 0.05) WBS than the other pork at d 2. After 7 d of storage, this difference had disappeared. Based on glycolytic potential, 30 of the H pigs were carriers of the Rendement Napole (RN) gene. When these pigs were excluded from the analysis, there was no difference in tenderness or tenderization of H, D, and B pork. The correlation between IMF and WBS was -0.11 at d 2, -0.21 at d 7, and -0.19 at d 14. In D pork, the relationship between IMF and WBS was linear, and IMF accounted for 47% of the differences in WBS. In H and B pork, the relationship between IMF and WBS was not significant. For each cross, the relationship between pHu and WBS was different; in D pork it was quadratic, in H pork WBS increased linearly, and in B pork there was no significant relationship between WBS and pHu. The 30 kDa/actin ratio, a measure of myofibrillar degradation, increased (P < 0.05) during storage. Differences in 30 kDa/actin ratio did not explain differences in pork tenderness or tenderization. Further research on determinants and mechanisms of pork tenderness and pork tenderization is needed before production of consistently tender pork will be possible. PMID- 11219449 TI - The calpain system in three muscles of normal and callipyge sheep. AB - Activities of mu- and m-calpain and of calpastatin were measured at four different times during postmortem storage (0, 1, 3, and 10 d) in three muscles from either callipyge or noncallipyge (normal) sheep. The weights of two muscles, the biceps femoris and the longissimus, are greater in the callipyge phenotype, whereas the weight of the infraspinatus is not affected. The activity of m calpain was greater (P < 0.05) in the biceps femoris and longissimus from callipyge than in those from normal sheep, but it was the same in the infraspinatus in the two phenotypes. The extractable activity of m-calpain did not change (biceps femoris and infraspinatus) or decreased slightly (longissimus) during postmortem storage. Extractable activity of mu-calpain decreased to zero or nearly zero after 10 d postmortem in all muscles from both groups of sheep. The rate of decrease in mu-calpain activity was the same in muscles from the callipyge and normal sheep. At all time points during postmortem storage, calpastatin activity was greater (P < 0.05) in the biceps femoris and longissimus from the callipyge than from the normal sheep, but it was the same in the infraspinatus from callipyge and normal sheep. Calpastatin activity decreased (P < 0.05) in all three muscles from both phenotypes during postmortem storage; the rate of this decrease in the callipyge biceps femoris and longissimus and in the infraspinatus from both the callipyge and normal sheep was slow, especially after the first 24 h postmortem, whereas calpastatin activity in the biceps femoris and longissimus from the normal sheep decreased rapidly. During postmortem storage, the 125-kDa calpastatin polypeptide was degraded, but the 80-kDa subunit of mu calpain was cleaved only to 76- and 78-kDa polypeptides even though extractable mu-calpain activity declined nearly to zero. Approximately 50 to 60% of total mu calpain became associated with the nonextractable pellet after 1 d postmortem. The myofibril fragmentation index for the biceps femoris and longissimus from normal sheep increased significantly during postmortem storage. The fragmentation index for the infraspinatus from the callipyge and normal sheep increased to an intermediate extent, whereas the index for the biceps femoris and longissimus from the callipyge did not change during 10-d postmortem storage. The results suggest that postmortem tenderization is related to the rate of calpastatin degradation in postmortem muscle and that calpastatin inhibition of the calpains in postmortem muscle is modulated in some as yet unknown manner. PMID- 11219450 TI - Dietary phosphorus and an inflammatory challenge affect performance and immune function of weanling pigs. AB - Ninety-six 3-wk-old pigs (6.3+/-0.12 kg initial BW) were allotted to one of eight treatments based on BW and litter origin to determine the effect of dietary phosphorus and an inflammatory challenge on performance and immune function. Four corn-soybean meal-based treatment diets were formulated to contain 0.16, 0.24, 0.32, or 0.40% available P. Monocalcium-dicalcium phosphate was used as the supplemental P source. The Ca:available P ratio was maintained at 2:1. To challenge the pigs, half of the pigs in each dietary treatment were injected i.m. with E. coli lipopolysaccharide (200 microg/kg of BW) on d 7 and 14. This resulted in a 2 x 4 factorial arrangement of treatments. Average daily gain for the 35-d study was increased linearly (P < 0.01) by increasing supplemental P. Average daily gain and ADFI were decreased (P < 0.05) by lipopolysaccharide injection. Serum P concentrations increased linearly (P < 0.01) with increasing supplemental P. Antibody titers to the injection of sheep red blood cells and ovalbumin on d 21 decreased linearly (P < 0.10) by increasing supplemental P. In vitro blastogenic response of lymphocytes to phytohemagglutinin (PHA) on d 25 was increased linearly (P < 0.05) by increasing supplemental P. Blastogenic response of lymphocytes to pokeweed mitogen on d 25 was not affected. On d 31, skinfold thickness 6 h following an intradermal injection of PHA was increased quadratically (P < 0.07) by increasing supplemental P. There were no P x lipopolysaccharide interactions for any immune response measure. In conclusion, increasing supplemental P increased ADG and enhanced cell-mediated immune response but decreased humoral immune response. PMID- 11219451 TI - Effects of postweaning dietary energy source on reproductive traits in primiparous sows. AB - An experiment was conducted to study the effects of major dietary energy source fed from weaning to ovulation or from ovulation to d 35 of pregnancy on reproductive traits in primiparous sows. Dietary energy sources were used to manipulate the plasma insulin concentration. One hundred thirteen sows were used in a split-plot design. From weaning to ovulation sows were fed at two times maintenance either a diet with tallow (Fat) or maize starch plus dextrose (Starch) as the major energy source. From ovulation onward, sows within each dietary group were alternately reassigned to either the Fat or the Starch diet and were fed at 1.25 times maintenance. Estrus detection was performed three times a day from d 3 to 9 after weaning and sows were inseminated each day of standing estrus. On d 35 of pregnancy, the sows were slaughtered and their reproductive tracts were removed. Plasma insulin concentration was higher in sows fed the Starch-rich diet than in sows fed the Fat-rich diet on d 4 after weaning (1.30 vs 0.97 ng/mL, P = 0.08) and on d 32 of pregnancy (1.20 vs 0.51 ng/mL, P < 0.001). Plasma glucose and IGF-I concentration on d 4 after weaning and d 32 of pregnancy did not differ between sows on the two dietary energy sources. The percentage of sows exhibiting estrus within 9 d after weaning was 52 and 67% for the Fat and Starch diet before ovulation, respectively (P = 0.11), whereas the weaning-to-estrus interval was 134 vs 123 h, respectively (P = 0.12). Survival analysis showed that sows fed the Fat-rich diet had a 1.6 times higher risk to remain anestrous until d 9 after weaning than sows fed the Starch-rich diet (P = 0.04). No effect of dietary energy source, either before or after ovulation, on uterine, placental, or embryonal development on d 35 of pregnancy was found. It can be concluded that the dietary energy source provided after weaning can affect the risk of sows to remain anestrous but does not affect uterine, placental, or embryonic traits. PMID- 11219452 TI - Liquid diets accelerate the growth of early-weaned pigs and the effects are maintained to market weight. AB - Piglets (n = 240, 11.0+/-0.1 d old, 3.93+/-0.05 kg) were allotted to one of four treatments in a 2 x 2 factorial arrangement to examine the effects of diet physical form and nursery environment during the first 14 d after weaning on growth to market weight. During the treatment period, pigs were housed (10 pigs/ pen) in either a conventional hot nursery (30 degrees C) or a segregated temperature nursery (cool ambient temp. of 24 degrees C, with enclosed hot-box hovers at 32 degrees C). Pigs in each environment were fed nutritionally identical diets in either liquid or dry-pellet form for 14 d. Subsequently, all pigs were fed identical dry diets and were housed in common grower-finisher facilities (penned by sex, five pigs/pen). At the end of the treatment period (d 14), pigs fed the liquid diet were 21% heavier than pigs fed the dry pellet diet (9.22 vs 7.60 kg; P < 0.001). Similarly, gain, feed intake, and gain/feed of liquid-fed pigs were 44%, 18%, and 22% greater, respectively, than observed for pigs fed the dry pellet diet. No main effect of environment was observed (P > 0.10); however, an interaction with diet physical form occurred during the early nursery period (P < 0.01). Pigs fed the liquid diet showed better performance in the conventional nursery, whereas pigs fed the dry pellet diet were favored in the segregated-temperature nursery. No major differences in growth performance or in ultrasound carcass measurements were detected during the growing-finishing period; however, the advantage in body weight of liquid-fed pigs gained during the first 2 wk postweaning was maintained to the end of the trial (113.9 vs 110.6 kg; P < 0.05). Pigs that were fed the early-nursery diet in liquid form reached market weight (110 kg) 3.7 d sooner than the dry-fed controls (P < 0.01). Estimates of lean gain (calculated from live ultrasound data) were unaffected, suggesting that composition of growth was not altered. Collectively, these results show that liquid feeding during early life can markedly accelerate piglet growth performance and that the growth advantage is maintained to market weight, with no evidence of compensatory gain in the dry-fed control pigs. PMID- 11219453 TI - In vitro fermentation characteristics of native and processed cereal grains and potato starch using ileal chyme from dogs. AB - Two in vitro experiments were conducted to evaluate the ability of small intestinal bacteria of dogs to ferment native and extruded cereal grains and potato starch and cereal grain and potato flours. Substrates included barley, corn, potato, rice, sorghum, and wheat. In addition to testing native grains and flours, extruded substrates also were tested. Substrates were extruded at low temperatures (LT; 79 to 93 degrees C) and high temperatures (HT; 124 to 140 degrees C) using a Wenger extruder (model TX-52). Substrates varied widely in concentrations of rapidly digestible starch (RDS), slowly digestible starch (SDS), resistant starch (RS), and total starch (TS). Extrusion of most substrates at HT vs LT resulted in increased RDS and decreased RS concentrations. Organic matter disappearance (OMD) values attributed to microbial fermentation for a 5-h period were as high as 27% for native extruded substrates (LT potato starch) and 39% for potato flour. Average OMD was higher for cereal and potato flours than for native extruded substrates (29.9 vs 25.4%). Average molar percentages of short-chain fatty acids produced from all substrates fermented for 5 h were 73, 14, and 13% (acetate, propionate, and butyrate, respectively). Average lactate production for substrates ranked as follows: flours > native and extruded cereal grains and potato starch (0.33 and 0.18 mmol/g OM, respectively). In vitro microbial fermentation of starches by ileal bacteria can be substantial and is affected by differences in starch source, fraction, and processed form. PMID- 11219455 TI - Effects of the perfusion of beta-, beta2-, or beta3-adrenergic agonists or epinephrine on in situ adipose tissue lipolysis measured by microdialysis in underfed ewes. AB - The effects of isoproterenol (ISO, a non-selective beta-agonist), terbutaline (TER, a selective beta2-agonist), CL316243 (CL, a selective beta3-agonist), and epinephrine (EPI, beta- and alpha2-agonist) on in situ lipolytic response of s.c. adipose tissue were investigated in vivo, using a microdialysis method to measure glycerol release, in 12 adult nonlactating and ovariectomized, underfed Lacaune ewes. All the adrenergic compounds were perfused for 120 min at 10(-6), 10(-5), and 10(-4) M. They had no lipolytic effect at 10(-6) M. Isoproterenol and EPI at 10(-5) and 10(-4) M enhanced, in the same way, maximal response and area under the concentration curve (AUC) of dialysate glycerol, thus suggesting that involvement of alpha2-adrenoceptors in the control of in situ lipolysis is of minor importance in underfed ewes. Terbutaline had only a slight lipolytic effect at 10(-5) M. This low effect could be due to a lower affinity of TER than of ISO for the beta2-adrenoceptors. The beta3-agonist, CL, had no lipolytic effect whatever the concentration perfused. Further studies are needed to prove the putative presence of beta3-adrenoceptors and their possible role in the ovine adipose tissue. PMID- 11219456 TI - The influence of the phase of the estrous cycle on sheep endometrial tissue response to lipopolysaccharide. AB - The effect of lipopolysaccharide on ovine endometrial tissue was examined at estrus (follicular phase) and during the luteal phase. Endometrial tissues were cultured with 0, 1, or 10 microg/mL lipopolysaccharide. After 24 h, culture supernates were harvested and analyzed for PGF2alpha, PGE2, 6-keto-PGF1alpha, thromboxane B2 (TXB2), and cysteinyl-leukotrienes (leukotrienes) using EIA. Homogenates of endometrial tissue were analyzed for prostaglandin endoperoxidase 1 (PTGS-1), and -2 (PTGS-2) as well as Type-I, -II, and -III nitric oxide synthase (NOS) by Western analysis. Follicular phase tissue produced more PGF2alpha (P < 0.001), TXB2 (P < 0.001), and leukotrienes (P < 0.02) than luteal tissue. Lipopolysaccharide increased PGE2 (P < 0.001) and TXB2 (P < 0.02) production by endometrial tissue. Elevations in these eicosanoids were likely due to the measured increases in PTGS-2 (P = 0.002) because no changes in PTGS-1 (P = 0.54) or Type-I, -II, or -III NOS (P > or = 0.20) occurred in endometrial tissue following lipopolysaccharide exposure. These data suggest that the phase of the estrous cycle regulates prostaglandin production by immune-challenged endometrial tissue. PMID- 11219454 TI - Effects of recombinant ovine leptin on in vitro lipolysis and lipogenesis in subcutaneous adipose tissue from lactating and nonlactating sheep. AB - Direct effects of recombinant ovine leptin on adipose metabolism in sheep were investigated. Lipolytic and lipogenic rates were assessed following preincubation of subcutaneous adipose tissue explants with recombinant ovine leptin. Leptin had no consistent effect on the basal (unstimulated) lipolytic rate in adipose tissue from wethers. Lipolytic rate measured in the presence of combinations of adenosine deaminase, isoprenaline, and N6-phenylisopropyl adenosine was unaffected by pretreatment with leptin. In lactating ewes, there was no relationship between increasing concentrations of leptin and basal lipolytic rate. Leptin had no effect on basal (unstimulated) lipogenesis, or on insulin stimulation or growth hormone inhibition of lipogenesis in adipose tissue from wethers. Lipogenesis in adipose tissue from lactating ewes was also unaffected by preincubation with leptin; however, at supraphysiological concentrations of leptin, there was a small reduction in the rate of insulin-stimulated lipogenesis. Leptin failed to induce phosphorylation of the signal transducers and activators of transcription, STAT 3 and STAT 5, in sheep adipocytes. These results suggest that leptin does not have a direct physiological effect on subcutaneous adipose tissue metabolism in sheep. PMID- 11219457 TI - Genetic variation in stimulated GH release and in IGF-I of young dairy cattle and their associations with the leucine/valine polymorphism in the GH gene. AB - Genetic variations in plasma GH concentrations before and following thyrotropin releasing hormone (TRH) stimulation and in IGF-I concentrations were studied in 11-mo-old Polish Friesian cattle (104 heifers and 110 bulls). A possible association between stimulated GH release, IGF-I, and the polymorphism in the GH gene causing substitution of leucine-Leu to valine-Val at amino acid position 127 of the protein was also investigated. The GH concentrations were determined in serial plasma samples collected every 15 min from 15 min before to 135 min after intravenous administration of 0.15 microg TRH/kg live weight. The analysis was performed on three variables: baseline (mean of samples at -15 and 0 min), peak (sample at 15 min after injection) and rate (peak minus sample at 60 min, divided by 45 min). The IGF-I concentrations were measured in plasma samples taken before the TRH stimulation. Additionally, first lactation records from the 75 cows earlier tested for GH release and IGF-I were used to study a possible association of milk production traits with GH genotypes. The data were analyzed by multivariate mixed linear models. The heritability of IGF-I reached a higher value (0.35) than variables baseline, peak, and rate (0.02, 0.14, and 0.14, respectively). The GH variables were positively genetically correlated with each other (0.22 to 0.93), whereas they had negative genetic correlations with IGF-I ( 0.26). The Val/Val genotypes reached the highest peak value compared with other GH genotypes (P > 0.01), whereas the Leu/Leu genotypes had the highest IGF-I concentrations (P < or = 0.05). Moreover, the Leu/Val heterozygotes were superior to others in milk and protein yields, whereas the Leu/Leu homozygotes reached the highest fat yield (P > or = 0.01). We conclude that GH peak, GH rate, and IGF-I are heritable traits in young dairy cattle and are affected by the Leu/Val polymorphism in the GH gene. PMID- 11219458 TI - Influence of intraduodenally infused olive and coconut oil on postprandial exocrine pancreatic secretions of growing pigs. AB - The effect of dietary vegetable oils differing in fatty acid composition that were infused directly into the duodenum on exocrine pancreatic secretions in pigs has not previously been studied. The objective of the present study was to determine the acute response of the exocrine pancreas to vegetable oils with various fatty acid profiles under prandial conditions. Six growing pigs (BW 13.2 kg) were surgically prepared with pancreatic duct catheters and duodenal reentrant T-cannulas. The animals were fed twice a day (1000 and 1600) a commercial weaner diet at a rate of 2% of BW. Beginning with the morning feeding, olive oil, coconut oil, or saline as a control were infused in boluses every 5 min in total 0.1% of BW over a period of 1 h directly into the duodenum according to a 3 x 3 Latin square design. Pancreatic juice was collected over a period of 4 h, beginning 1 h preprandially (0900) until 3 h postprandially (1300). A time effect was observed after the infusion of olive oil on the volume of secretion, on protein contents and outputs, as well as on lipase contents and outputs and on colipase contents. The infusion of saline and coconut oil changed the runs of the curves for lipase and colipase outputs. No time x treatment interactions were observed regarding volume of secretion, protein contents and outputs, trypsin contents and outputs, and lipase outputs. The runs of the curves for lipase contents were different between the olive oil and saline treatment and between the olive oil and coconut oil treatment. The runs of the curves for the olive oil and saline treatment differed from each other regarding colipase contents. Pooled values of colipase outputs were elevated after coconut oil treatment, and a positive correlation between trypsin and colipase contents was found. Under prandial conditions, the exocrine pancreas responds differently in its acute secretion to different vegetable oils due to the differences in the fatty acid profiles. PMID- 11219459 TI - Genetic and phenotypic parameters for dietary selection of mountain big sagebrush (Artemisia tridentata Nutt. ssp. vaseyana. AB - The heritability of diet selection for mountain big sagebrush (Artemisia tridentata Nutt. ssp. vaseyana [Rydb] Beetle) by grazing sheep was estimated from fecal samples collected from 549 Rambouillet ewes. Fecal samples were collected in September and October during 1996 and 1997 from free-grazing ewes on intermountain sagebrush-bunchgrass rangelands at the U.S. Sheep Experiment Station in Idaho. The total number of fecal samples was 1,949. Fecal samples were evaluated for composition of big sagebrush by near-infrared spectroscopy. Percentage of sagebrush in the diet was less in September than in October (21.6 vs 31.7%, respectively). Single-trait and bivariate derivative-free REML analyses were performed to genetically compare percentage of sagebrush in the diet in September and October. Heritability estimates were similar between September and October measurements (0.25 and 0.28, respectively). The genetic correlation between September and October percentages of sagebrush in the diet was high (0.91), implying that there is strong genetic similarity between September and October measurements and that an annual measurement may be sufficient for selection. These results contribute to a greater understanding of dietary preferences in freely grazing sheep, and suggest opportunities to improve production efficiency and forage management through selection for dietary preferences. PMID- 11219460 TI - Performance of light vs heavy steers grazing Plains Old World bluestem at three stocking rates. AB - Live weight gains of light and heavy calves grazing Plains Old World bluestem at three stocking rates were evaluated during the summers of 1997 and 1998. Initial weights of mixed-breed light-weight steers (LHT) were 141 SD = 17 kg (n = 214) in 1997 and 160 SD = 23 kg (n = 193) in 1998. Initial weights of mixed-breed heavy steers (HWT) were 265 SD = 17 kg (n = 115) in 1997 and 248 SD = 13 kg (n = 126) in 1998. Initial stocking rates for both sizes of steers were as follows: light, 392 kg of live weight/ha; moderate, 504 kg of live weight/ha (increased to 616 kg live weight/ha in 1998); and heavy, 840 kg of live weight/ ha. Averaged gain and gain/hectare are reported as stocking rate by steer type within year. Heavy steers had greater ADG than LHT steers during both years. Forage intake, expressed as a percentage of BW, was greater (P = 0.05) for LHT (3.1%) than for HWT (2.8%) calves. Grazing time (min/d; 1998 only) was greater (P = 0.05) for LHT (665) than for HWT (624) steers. Forage CP and in vivo digestible organic matter (DOM) were slightly greater (P < 0.05) in pastures grazed by HWT vs LHT cattle. Gain/hectare was greater (P < 0.05) for LHT than for HWT calves at all three stocking rates during both years. A linear decline in ADG was observed (P < 0.07) as stocking rates increased for HWT steers in 1997 and LHT steers in 1998. However, ADG did not decline with increasing stocking rate for LHT calves during 1997 or HWT calves during 1998. Forage intake was not different among stocking rates in either 1997 or 1998. Grazing time was greatest (P < 0.05) for steers in the moderate and heavy stocking rates. Forage in vivo DOM decreased (P < 0.05) as stocking rate increased. Both LHT and HWT steers had lower (P < 0.05) ADG at all three stocking rates during 1998 compared with 1997. Despite lower ADG, LHT steers had greater gain/hectare than HWT steers during both 1997 and 1998. PMID- 11219461 TI - Hydrolyzable carbohydrates in pasture, hay, and horse feeds: direct assay and seasonal variation. AB - Carbohydrates may be hydrolyzed or fermented in the digestive tract, and this distinction is important for the evaluation of the diet of herbivores. Both hydrolyzable and fermentable carbohydrates are included in the nonstructural carbohydrate (NSC) fraction as estimated by difference using proximate analysis. Our objectives were to measure hydrolyzable carbohydrates in forages and concentrates, to compare these values with nonstructural carbohydrate, to test for prediction of hydrolyzable carbohydrate concentration in forages from its near-infrared spectrum, and to examine seasonal variation of carbohydrates in pasture. Samples of forages (107) and concentrates (25) were collected, dried, ground, and analyzed for NSC (calculated as 100 - water - CP - fat - ash - NDF), hydrolyzable carbohydrate (CHO-H, direct analysis), and rapidly fermentable carbohydrate (NSC minus CHO-H). Hydrolyzable carbohydrate accounted for 97% or more of the NSC in the concentrates but only 33% in pasture and hay. A two-term polynomial equation fit all the data: CHO-H = 0.154 x NSC + 0.00136 x NSC2, R2 = 0.98, P < 0.0001, n = 132. In 83 pasture samples, CHO-H concentrations were predicted by near-infrared spectra with a calibration R2 of 0.97, a mean of 48 g/kg, and a SE of calibration of 3.5 g/kg DM. In pasture samples collected between September 1995 and November 1996, the coefficient of variation was 31% for both CHO-H and rapidly fermentable carbohydrate (CHO-FR); the largest increments were 31 g/kg of CHO-H from September to October and 41 g/kg of CHO-FR from February to March. The increased risk of certain diseases, such as laminitis and colic, that have been previously associated with an abrupt overload of NSC may be more precisely attributed to CHO-H in grain concentrates, and to CHO-H as well as CHO-FR in pastures. PMID- 11219462 TI - Retention time of macerated alfalfa hay and silage in sheep. AB - Fresh alfalfa was mowed and conditioned mechanically at four levels: a control (rubber rolls), macerated once (a single passage through three finely corrugated rolls set at 1-mm clearance), macerated twice (two passages), and macerated thrice (three passages). Alfalfa was then field-wilted either for 45 h and conserved as chopped silage at 30% dry matter (DM) or for 94 h and stored as baled hay at 85% DM. The eight forage treatments (four mechanical conditioning levels x two conservation systems) were fed to 24 sheep (three replications per treatment) during 5 wk. At the beginning of wk 5, a 15-g sample of chromium mordanted forage (3.5% Cr) was fed to each sheep, and feces samples were collected at 30 different times over 7 d, between 10 h and 168 h after Cr ingestion. Four models were used to estimate the passage rates, the time delay, and the mean retention time (MRT). A two-compartment time-dependent model and a multicompartment model produced the best fit (average r2 of 0.96) to represent the Cr concentration in the feces over time. When compared with alfalfa hay, alfalfa silage had a higher (P < 0.01) time-dependent turnover rate (0.0949 vs 0.0733/h), a lower (P = 0.03) time delay (9.1 vs 11 h), and a lower (P = 0.04) MRT (57.8 vs 64.4 h). Maceration did not affect significantly (P > 0.10) the time delay or the MRT. However, the MRT of macerated alfalfa hay tended to be higher than the MRT of control hay. Experimental data based on marker concentration in the feces can be used satisfactorily to assess differences in MRT between treatments, but they should be used with caution to estimate the partition of retention time within the gastrointestinal tract. PMID- 11219464 TI - The amino acid profiles of the whole plant and of four plant residues from temperate and tropical forages. AB - This study compared the amino acid (AA) profile of five residues (original forage, borate-phosphate buffer residue (BPR), neutral detergent fiber residue with (NDF+) and without (NDF-) sodium sulfite, and acid detergent fiber residue (ADF). Fourteen grasses and legumes from tropical and temperate regions were used in this study. The use of sodium sulfite did not affect the NDF concentration, but the NDF insoluble protein was lower (P < 0.05) in the NDF+ than in the NDF- (3.9 vs 4.5% DM, respectively). For all of the amino acids tested, the amino acid content, expressed as a percentage of CP, was lower in the ADF residue than in the original forage. There were no differences in the amino acid concentrations of the NDF- and NDF+ extracts (P > 0.05). Only in the case of methionine was there a difference in the amount of amino acid when the original forage was compared with the BPR (1.84 vs 1.45 % CP). When the AA profile of each residue was corrected for the AA content of the ADF, no difference was observed between the AA profile of the original forage and of the BPR (P > 0.05). Similar to the result without correction for the amino acids in ADF, the AA profiles of the NDF+ and NDF- fractions were similar (P > 0.05). From this result, we infer that the sodium sulfite had similar effects on all AA in the NDF residue that we tested. There were differences in amino acid concentrations in the original forage and the NDF residues for several amino acids (Met, Cys, Lys, Thr, Arg, Ile, Leu, and Phe) (P < 0.05). When the amino acid values of the original forage and the BPR were used with animal data in the Cornell Net Carbohydrate and Protein System model, few differences in animal predicted performance were evident. These findings suggest that the AA profile of the original forage can be used to predict the AA profile of the undegraded intake protein instead of using the borate-phosphate buffer residue for amino acid analyses. This would simplify obtaining feed amino acid values for use in the Cornell Net Carbohydrate and Protein System. PMID- 11219463 TI - Fermentation characteristics and ruminal ciliate protozoal populations in cattle fed medium- or high-concentrate barley-based diets. AB - Fermentation characteristics were measured and numbers and distribution by genera of ciliate protozoa were determined in ruminal fluid samples collected from 10 ruminally cannulated steers during the first 30 d of their being fed barley-based diets containing 62% (Medium Barley) or 95% (High Barley) barley grain (DM basis). Ruminal samples were collected at 5-d intervals over the 30-d periods beginning after adaptation (i.e., at the first full feeding of each diet). Ruminal pH and ammonia concentrations were lower (P < 0.001) with the High Barley than with the Medium Barley diet. Concentrations of total VFA and propionate and amylase activity of ruminal fluid were higher (P < 0.001) on High Barley than on Medium Barley. Total protozoal numbers in ruminal fluid were 42% lower (P < 0.05) on High Barley (470 x 10(3)/mL) than on Medium Barley (804 x 10(3)/mL). On Medium and High Barley diets, respectively, Entodinium spp. made up 89 and 91% of the ciliate protozoal populations. With the Medium Barley diet, relative proportions of Dasytricha, Ophryoscolex, Ostracodinium, Diplodinium, and Metadinium spp. in the total ciliate population were 4.5, 0.4, 0.5, 0.7, and 0.3%, respectively. When the High Barley diet was fed, these genera were not detected. In a subsequent survey, ruminal samples were collected from 200 finishing cattle at slaughter. Average protozoal population was 328 x 10(3)/mL, and Entodinium spp. constituted 97% of the total. These data demonstrate that a large population of Entodinium spp. can persist in the rumen of cattle fed high barley grain-based finishing diets. PMID- 11219465 TI - Effect of ruminal protein degradability on growth and N metabolism in growing beef steers. AB - The objective of two experiments was to correlate plasma levels of urea N (PUN) and the percentage of urine N in the form of urea (UUN) to weight gain in response to different dietary protein regimens for growing Angus steers. In Exp. 1, 60 steers (302 kg BW) were assigned to various levels of dietary N (control plus supplemental N to provide from 100 to 400 g more crude protein daily) within two sources of supplemental N (soybean meal [SBM] or a mixture of two parts corn gluten meal:one part blood meal [CGM:BM]). In Exp. 2, 27 steers (229 kg BW) were fed two levels of SBM, and half of the steers received growth-promoting implants. Steers were housed in groups of 12 and fed individually for 84 d in both experiments. Corn silage was fed at a restricted rate to minimize orts. Jugular blood and urine samples were collected during the experiments. In Exp. 1, maximal ADG of steers fed SBM (1.0 kg) was reached with 671 g/d total crude protein, or 531 g/d metabolizable protein. Maximal ADG of steers fed CGM:BM (0.91 kg) was reached with 589 g/d total crude protein, or 539 g/d metabolizable protein. The DMI was higher (P < 0.07) for steers fed SBM (6.37 kg/d) than for steers fed CGM:BM (6.14 kg/d). Increasing ruminal escape protein from 36% (SBM) to 65% (CGM:BM) of CP decreased (P < 0.05) endogenous production of urea, as evidenced by lower concentrations of urea in blood and lower UUN. In Exp. 2, increasing supplemental protein from 100 to 200 g/d increased (P < 0.05) ADG and PUN. Implants lowered (P < 0.05) UUN, particularly at the higher level of supplemental protein. Protein supplementation of growing steers can be managed to maintain acceptable ADG yet decrease excretion of urea in the urine. PMID- 11219466 TI - Ergot alkaloid transport across ruminant gastric tissues. AB - Ergot alkaloids cause fescue toxicosis when livestock graze endophyte-infected tall fescue. It is generally accepted that ergovaline is the toxic component of endophyte-infected tall fescue, but there is no direct evidence to support this hypothesis. The objective of this study was to examine relative and potential transport of ergoline and ergopeptine alkaloids across isolated gastric tissues in vitro. Sheep ruminal and omasal tissues were surgically removed and placed in parabiotic chambers. Equimolar concentrations of lysergic acid, lysergol, ergonovine, ergotamine, and ergocryptine were added to a Kreb's Ringer phosphate (KRP) solution on the mucosal side of the tissue. Tissue was incubated in near physiological conditions for 240 min. Samples were taken from KRP on the serosal side of the chambers at times 0, 30, 60, 120, 180, and 240 min and analyzed for ergot alkaloids by competitive ELISA. The serosal KRP remaining after incubation was freeze-dried and the alkaloid species quantified by HPLC. The area of ruminal and omasal tissues was measured and the potential transportable alkaloids calculated by multiplying the moles of transported alkaloids per square centimeter of each tissue type by the surface area of the tissue. Studies were conducted to compare alkaloid transport in reticular, ruminal, and omasal tissues and to determine whether transport was active or passive. Ruminal tissue had greater ergot alkaloid transport potential than omasal tissue (85 vs 60 mmol) because of a larger surface area. The ruminal posterior dorsal sac had the greatest potential for alkaloid transport, but the other ruminal tissues were not different from one another. Alkaloid transport was less among reticular tissues than among ruminal tissues. Transport of alkaloids seemed to be an active process. The alkaloids with greatest transport potential were lysergic acid and lysergol. Ergopeptine alkaloids tended to pass across omasal tissues in greater quantities than across ruminal tissues, but their transport was minimal compared to lysergic acid and lysergol. PMID- 11219467 TI - Rapid communication: Microsatellites isolated from BAC clones containing v-akt1 murine thymoma viral oncogene homolog 1 and bradykinin receptor B2 assigned to sheep chromosome 18 by linkage analysis. PMID- 11219468 TI - Rapid communication: Nucleotide sequences of two isoforms of porcine micromolar calcium-activated neutral protease 1 cDNA. PMID- 11219469 TI - Rapid communication: Linkage mapping of the porcine micromolar calcium-activated neutral protease 1 (mu-calpain) gene on SSC2. PMID- 11219470 TI - Rapid communication: Genetic linkage and physical mapping of the porcine lipopolysaccharide-binding protein (LBP) gene. PMID- 11219472 TI - The new administration and Medicare reform. PMID- 11219471 TI - Comparison of 26-week efficacy and tolerability of telmisartan and atenolol, in combination with hydrochlorothiazide as required, in the treatment of mild to moderate hypertension: a randomized, multicenter study. AB - OBJECTIVE: This study was undertaken to compare the efficacy and tolerability of telmisartan, a novel antihypertensive agent, and atenolol, a well-established beta-blocker, in the treatment of mild to moderate hypertension. METHODS: This 26 week, multicenter, randomized, double-blind, double-dummy, parallel-group, titration-to-response study compared doses of telmisartan (40 mg titrated to 80 mg titrated to 120 mg) with atenolol (50 mg titrated to 100 mg) required to achieve diastolic blood pressure (DBP) control (< or = 90 mm Hg or a decrease from baseline of > or = 10 mm Hg). Open-label hydrochlorothiazide (HCTZ) 12.5 or 25 mg was added if needed according to a prespecified titration rule. Men and women aged > 18 years with mild to moderate hypertension (morning mean supine DBP [SDBP] > or = 95 mm Hg and < or = 114 mm Hg) were eligible to participate. Patients with significant cardiovascular, metabolic, hepatic, or renal dysfunction or chronic obstructive pulmonary disease were excluded. The primary efficacy end point was trough SDBP response at 26 weeks; secondary efficacy end points included changes from baseline at trough in both standing and supine DBP and systolic blood pressure (SBP), and heart rate after 4, 8, 16, and 26 weeks; SBP control (reduction from baseline of > or = 10 mm Hg); normalization of supine SDBP to < or = 90 mm Hg; and the need for add-on HCTZ. Changes in quality of life were also examined. Adverse events were obtained from spontaneous reporting and recorded. Serious adverse events were reported to the sponsor according to predefined timelines. RESULTS: A total of 533 patients from 49 centers participated. Patients' mean age was 57.9 years (range, 22-79 years); 55.9% (298/533) of the population was male and 98.1% (523/533) was white. Of the 533 patients randomly assigned to treatment and included in the safety analysis, 520 (97.6%) were included in the efficacy analysis; 346 received telmisartan and 174 received atenolol. A total of 489 patients (91.7%) completed the study (325 [93.9%], telmisartan; 164 [94.2%], atenolol). Full SDBP response (trough SDBP < or = 90 mm Hg and/or a reduction from baseline of > or = 10 mm Hg) was observed in 84% and 78% of telmisartan- and atenolol-treated patients, respectively; this difference was not statistically significant. Final SBP/DBP reductions of 20.9/14.4 mm Hg were observed for the telmisartan regimen versus 16.7/13.3 mm Hg for the atenolol regimen; only the difference in SBP was significant (P = 0.005). Reduction from baseline in SBP of > or = 10 mm Hg was achieved by 80% of telmisartan-treated and 68% of atenolol-treated patients (P = 0.003). Adverse events were reported by 52.7% of patients given telmisartan and 61.2% of patients given atenolol; this difference was not statistically significant. Most events were mild or moderate. Although fatigue and male impotence were more common in atenolol-treated patients (3.4% and 4.0%, respectively), the incidence of these adverse events was too low to differentiate statistically. CONCLUSIONS: Telmisartan appears to be at least as effective as atenolol in the treatment of mild to moderate hypertension and may be better tolerated. PMID- 11219473 TI - Treatment satisfaction, functional status, and health-related quality of life of migraine patients treated with almotriptan or sumatriptan. AB - BACKGROUND: Patient-reported outcomes, such as treatment satisfaction, functional status, and health-related quality of life (HRQOL) are essential components of migraine research. Almotriptan is a new selective serotonin 1B/1D agonist triptan migraine treatment. OBJECTIVE: The purpose of this double-blind, multicenter, randomized, parallel-group study was to compare treatment satisfaction, functional status, and HRQOL of patients treated with oral almotriptan versus sumatriptan, the leading triptan on the market. METHODS: Migraine patients, aged 18 to 71 years, took equivalent oral doses of 12.5 mg almotriptan or 50 mg sumatriptan for the abortive treatment of a migraine headache. Treatment satisfaction differences between study groups were assessed using a 6-item measure to determine patients' satisfaction with pain relief and satisfaction with side effects 48 hours after drug administration. Functional status was assessed by analyzing the change in patients' ability to perform normal activities during the course of the migraine. HRQOL was compared between treatment groups at 24 hours using the Migraine Quality of Life Questionnaire. End points were assessed using entries from patients' 48-hour diaries. RESULTS: A total of 1173 patients were treated with almotriptan or sumatriptan. There were no significant differences between the 2 treatment groups in terms of satisfaction with pain relief; however, patients in the almotriptan group were significantly more satisfied (less bothered) with side effects than those receiving sumatriptan (P = 0.016). Functional status and HRQOL outcomes were not significantly different between groups. CONCLUSIONS: In this study, migraine patients treated with almotriptan were significantly more satisfied with the side effect profile of the drug than patients treated with sumatriptan. The results of this study may help inform practicing physicians and neurologists about the potential treatment satisfaction advantages of almotriptan. PMID- 11219474 TI - Ovarian carcinoma: care and survival in a community-based population. AB - BACKGROUND: Previous studies of the management and costs of ovarian cancer have been based on data from oncology practices. Such studies may exclude patients who are not candidates for treatment and may not account for costs incurred during diagnosis or primary treatment. OBJECTIVE: The purpose of this study was to describe the epidemiology, management, and costs of care of ovarian cancer in a geographically defined population to better reflect the total spectrum of the disease and its care. METHODS: We conducted a retrospective review of the medical records of all residents of Olmsted County, Minnesota, who received a first diagnosis of epithelial ovarian carcinoma (including postmortem diagnoses) between 1985 and 1997. RESULTS: Of the 107 women with a new diagnosis of ovarian cacinoma, 42 (39%) had stage I or II tumors at the time of diagnosis. The mean age of the patients at the time of diagnosis was 64.7 years, and 20% were nulliparous. The diagnostic assessment for ovarian carcinoma was initiated by a family physician or internist in 50% of cases and by an obstetrician or gynecologist in 16% of cases. One hundred two patients (95%) underwent surgical treatment, and 80 (75%) received primary chemotherapy. The 5-year survival rate was 88% in those with stage I or II tumors and 17% in those with stage III or IV tumors. The mean charges for secondary care were higher than those for primary care ($36,110 vs $32,367; P < 0.05) in those receiving both types of therapy. Fifty percent of those dying of ovarian cancer received hospice care for a mean of 39.0 days before death. CONCLUSIONS: Most assessments leading to a diagnosis of ovarian carcinoma were initiated by primary care physicians. In this community based population, early-stage and low-grade tumors were common (> or = 30%) and were associated with lower costs of care and higher 5-year survival rates. Total treatment costs for those requiring secondary therapy were approximately twice the costs for those requiring primary treatment only, with approximately 50% of costs associated with inpatient care. PMID- 11219475 TI - Delphi panel study of current hypertension treatment patterns. AB - OBJECTIVE: The purpose of this study was to assess whether, and to what extent, usual practice in the management of patients with mild to moderate hypertension differs from that recommended in the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). The results were used as input for a clinical decision analytic model to assess the cost-effectiveness of a new treatment for hypertension. METHODS: A Delphi panel survey of general practitioners and cardiologists in the United States was conducted to determine current strategies for the treatment of mild to moderate uncomplicated hypertension. The purpose of the panel survey was to reach consensus on 3 key facets of the JNC-VI guidelines and how they relate to the respondents' clinical practices: (1) the definition of mild to moderate hypertension, (2) the treatment that adult patients with uncomplicated mild to moderate hypertension should receive, and (3) the management of patient follow up. RESULTS: Of the 20 physicians contacted for the survey, 10 responded to both rounds of the questionnaire. There was considerable variation in the responses for defining the ranges of healthy, acceptable, unacceptable, and serious blood pressure. In general, the Delphi panel respondents cited higher limits than stated in the JNC-VI guidelines. Physicians followed the guidelines approximately 60% of the time. Primary determinants of initial drug choice among the panelists were comorbid conditions and the severity of hypertension; patients' age, race, and sex were secondary determinants. Follow-up typically occurred 1 month after therapy initiation. Panelists reported titrating the dose of new therapies upward once or twice before discontinuing the drug for lack of efficacy. Once adequate blood pressure control was achieved, patient follow-up was reported to occur every 3 to 4 months. CONCLUSIONS: This Delphi panel study highlights the differences between clinical practice and the JNC-VI guidelines in the treatment of hypertension. The results were used as a basis for defining a structure for a cost-effectiveness model and provided the management practice and prescribing practice patterns required by the model. PMID- 11219476 TI - The importance of health-related quality-of-life data in determining the value of drug therapy. AB - BACKGROUND: The rapid evolution of outcomes research during the last decade has led to increasing emphasis on measures of health-related quality of life (HRQOL). However, the relatively recent advent of these measures makes it difficult to decide how much weight to attribute to them in decisions about the value of drug therapy. OBJECTIVE: The aim of this article is to discuss the factors that affect the relative importance of HRQOL data in determining the value of drug therapy. CONCLUSIONS: The relative importance of HRQOL data depends on the type of condition and the type of treatment. In chronic conditions, HRQOL may be considered a primary measure of efficacy. In acute conditions, HRQOL is not likely to be a primary efficacy measure, although excluding HRQOL measures may lead to an underestimation of treatment effects. Measures of HRQOL are also likely to be important in the assessment of palliative treatments and, to some extent, preventive treatments (primarily in the measurement of adverse effects). HRQOL measures will be less important in the assessment of curative treatments because these types of treatment are most relevant in acute conditions. PMID- 11219477 TI - Sildenafil citrate: a therapeutic update. AB - BACKGROUND: Since its approval by the US Food and Drug Administration in March 1998, sildenafil citrate has been used by millions of men for the treatment of erectile dysfunction. Recent studies and consensus reports have expanded our understanding of its efficacy, safety, contraindications, and drug interactions. OBJECTIVE: This paper reviews recent studies of the efficacy of sildenafil, its adverse effects and drug interactions, and socioeconomic factors involved in its use, with a focus on specific patient populations (prostate cancer, diabetes mellitus, ischemic heart disease, spinal cord injuries, neurologic disorders). METHODS: Clinical studies, case reports, and commentaries and editorials concerning sildenafil published in the international literature between January 1999 and August 2000 were identified through searches of MEDLINE, PREMEDLINE, and International Pharmaceutical Abstracts, using the terms sildenafil, Viagra, and erectile dysfunction. RESULTS: Sildenafil has demonstrated effectiveness in men with erectile dysfunction associated with prostatectomy, radiation therapy, diabetes mellitus, certain neurologic disorders, and drug therapy (eg, selective serotonin reuptake inhibitors [SSRIs]). It has not been as effective in women with sexual dysfunction, with the exception of SSRI-associated sexual dysfunction. Some disorders unrelated to sexual dysfunction (eg, esophageal motility dysfunction) may also respond to sildenafil. In the general population, sildenafil is considered to have an acceptable tolerability profile; however, patients with moderate to severe cardiovascular disease or those taking nitrate therapy are at increased risk for potentially serious cardiovascular adverse effects with sildenafil therapy. In addition, patients taking drugs that inhibit the cytochrome P450 3A4 isozyme, which metabolizes sildenafil, may experience increased drug concentrations and possible toxicity from normal doses of sildenafil. CONCLUSIONS: Sildenafil is an effective first-line therapy for erectile dysfunction in men. The decision to prescribe this agent should include such considerations as the cost-risk-benefit balance, patient access, drug distribution pathways, and prescription drug coverage. PMID- 11219478 TI - Quinupristin/dalfopristin: a therapeutic review. AB - BACKGROUND: The proliferation of multidrug-resistant gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium (VREF), has created a pressing need for effective alternative antibiotics. Quinupristin/dalfopristin is a new combination streptogramin product with a selective spectrum of antibacterial activity, mainly against gram-positive aerobic bacteria. It has been assessed primarily in emergency-use protocols, in hospitalized patients with skin and skin-structure infections, and in patients with VREF bacteremia. OBJECTIVES: The objectives of this review were to summarize important results of in vitro microbiologic studies; to provide information on relevant pharmacokinetic parameters, drug interactions, and Y-site compatibility; and to assess efficacy and safety data from clinical studies of quinupristin/dalfopristin. METHODS: Articles included in this review were identified by a MEDLINE search of the literature published between 1966 and September 2000 using the terms Synercid, quinupristin, and dalfopristin. Additional articles were retrieved from the reference lists of articles identified in the MEDLINE search. RESULTS: In vitro analysis of the spectrum of activity of quinupristin/dalfopristin has confirmed its relatively selective coverage of gram-positive aerobic bacteria. Both quinupristin and dalfopristin undergo hepatic metabolism and are extensively excreted in the feces. Combination quinupristin/dalfopristin inhibits the cytochrome P450 3A4 pathway, and caution is warranted with concomitant use of other medications eliminated via this pathway. In trials in patients with VREF infections, treatment success with quinupristin/dalfopristin varied depending on the site of infection, ranging from 51.9% in bacteremia of unknown origin to 88.9% in urinary tract infections. The results of comparative clinical trials suggest that quinupristin/dalfopristin has similar efficacy to that of commonly used antibiotics, including cefazolin, oxacillin, and vancomycin, in patients with skin and skin-structure infections or nosocomial pneumonia. The most frequently reported adverse effects with administration of quinupristin/dalfopristin were infusion-site inflammation, pain, and edema; other infusion-site reactions; and thrombophlebitis. Arthralgia, myalgia, nausea, diarrhea, vomiting, and rash occurred in 2.5% to 4.6% of patients and were the most frequently reported systemic adverse events. CONCLUSIONS: Outcomes data from clinical trials indicate that quinupristin/dalfopristin has the potential to play an important role in the treatment of bacteremia, complicated skin and skin-structure infections, and nosocomial pneumonia caused by VREF. Issues of bacterial resistance to quinupristin/dalfopristin and other appropriate uses of this combination agent remain to be elucidated. PMID- 11219480 TI - Pharmacokinetics of levormeloxifene in young versus elderly postmenopausal women. AB - BACKGROUND: Physiologic changes of aging may affect processes of drug absorption and distribution, in some cases necessitating age-dependent dose adjustment. OBJECTIVE: The possibility of age dependence in the pharmacokinetic behavior and tolerability of levormeloxifene was investigated in a single-center, open-label study. METHODS: The study comprised 2 groups of healthy postmenopausal women: group A included younger subjects (50-60 years) and group B included elderly subjects (> or = 66 years). All subjects received a single 40-mg tablet of levormeloxifene base. Blood samples were collected immediately before drug intake and at several points after administration, through day 34. Peak plasma concentration, time to maximum plasma concentration, area under the plasma concentration-time curves from zero to the last quantifiable value and to infinity, and terminal half-life were calculated for levormeloxifene and compared between age groups. RESULTS: Of 29 subjects enrolled, 28 (15 group A, 13 group B) completed the study. The ages of the women in group A ranged from 50 to 58 years and in group B from 66 to 79 years. No serious adverse events were reported. Ten subjects experienced 17 adverse events, of which 2 (abdominal pain and vaginal hemorrhage) were judged to be possibly related to study drug. There was no noticeable difference between age groups in the frequency of adverse events or laboratory abnormalities. The plasma concentration-time curves of levormeloxifene were indistinguishable between age groups up to 48 hours after dosing. From 72 hours onward, the mean plasma concentration-time curve was approximately 20% higher and the area under the curve was approximately 19% greater in the older subjects compared with the younger subjects. However, no statistically significant differences were observed between groups in any of the pharmacokinetic parameters, except for the elimination rate constant. The difference in mean elimination half-life was 25 hours (group A, 126 hours; group B, 151 hours). CONCLUSION: The findings suggest that it is not necessary to adjust the dose of levormeloxifene on the basis of age in postmenopausal women. However, these results need confirmation in a multiple-dose setting under steady state conditions--that is, as the drug is intended to be used clinically. PMID- 11219479 TI - Comparison of the efficacy and tolerability of fluvastatin extended-release and immediate-release formulations in the treatment of primary hypercholesterolemia: a randomized trial. AB - BACKGROUND: A new extended-release (ER) formulation of fluvastatin 80 mg has been developed for once-daily treatment of primary hypercholesterolemia. OBJECTIVE: The purpose of this study was to compare the lipid-lowering efficacy and tolerability of fluvastatin ER (80 mg once daily) versus fluvastatin immediate release (IR) (40 mg once or twice daily). METHODS: Following a 4-week placebo/dietary run-in period, patients with primary hypercholesterolemia type IIa or IIb (low-density lipoprotein cholesterol ILDL-C] > or = 160 mg/dL and triglycerides [TG] < or = 400 mg/dL) were randomized (2:1:1) to receive fluvastatin ER 80 mg once daily at bedtime (QPM), fluvastatin IR 40 mg QPM, or fluvastatin IR 40 mg BID for 24 weeks. Patients who had homozygous familial hypercholesterolemia; type I, III, IV, V, or secondary hyperlipoproteinemia; diabetes; or evidence of liver or renal impairment were excluded. At weeks 0, 2, 4, 8, 12, 16, 20, and 24 of the active-treatment period, levels of LDL-C, high density lipoprotein cholesterol (HDL-C), TG, and total cholesterol (TC) were measured. RESULTS: Of the 1183 patients enrolled, 695 were randomly assigned to treatment--346 to fluvastatin ER 80 mg QPM, 174 to fluvastatin IR 40 mg QPM, and 175 to fluvastatin IR 40 mg BID. Patients were well matched between groups, with a mean age of approximately 56 years and body mass index of 27 kg/m2; 56.0% of patients (389/695) were female and 97.7% (679/695) were white. Fluvastatin ER 80 mg QPM lowered LDL-C levels significantly more than did fluvastatin IR 40 mg QPM (33.7% vs 24.4%; P < 0.001) and as effectively as fluvastatin IR 40 mg BID (33.9%). More than half of the patients administered fluvastatin ER 80 mg QPM and IR 40 mg BID achieved reductions in LDL-C levels of > or = 35%; more than half of those administered fluvastatin IR 40 mg QPM experienced reductions in LDL-C levels of > or = 25%. The mean reductions in LDL:HDL ratio, TC, and apolipoprotein B levels in the fluvastatin ER 80 mg QPM group were significantly greater than the reductions in the IR 40 mg QPM group (P < 0.001). In patients with mixed dyslipidemia, fluvastatin ER 80 mg reduced triglycerides by 21.8% (median 28%) and increased HDL-C by 14.5%. Fluvastatin ER 80 mg QPM was well tolerated, with incidences of clinically notable elevations in alanine aminotransferase, aspartate aminotransferase, and creatine kinase levels and musculoskeletal adverse events comparable to those in the IR 40 mg QPM group. CONCLUSION: The ER 80-mg formulation of fluvastatin is effective and well tolerated as a once-daily starting and maintenance treatment for primary hypercholesterolemia. PMID- 11219481 TI - Comparison of the efficacy of extended-release clarithromycin tablets and amoxicillin/clavulanate tablets in the treatment of acute exacerbation of chronic bronchitis. AB - BACKGROUND: Clarithromycin has established efficacy and safety in the treatment of respiratory infections. OBJECTIVE: This study examined the efficacy and safety of a new extended-release formulation of clarithromycin compared with amoxicillin/clavulanate in the treatment of acute exacerbation of chronic bronchitis (AECB). METHODS: This phase IIIB, multicenter, randomized, parallel group, investigator-blinded study in patients with AECB and productive cough with purulent sputum compared treatment with extended-release clarithromycin (two 500 mg tablets once daily for 7 days) and amoxicillin/clavulanate (one 875-mg tablet twice daily for 10 days). Assessments were performed before treatment, between study days 10 and 12 (or within 48 hours after premature discontinuation), and between study days 17 and 21 (test of cure). RESULTS: Of 287 patients randomized and treated, 270 were clinically evaluable (137 clarithromycin, 133 amoxicillin/clavulanate). Treatment groups were well matched in terms of demographic characteristics, medical condition, and history. Among clinically evaluable patients at test of cure, 85% and 87% of clarithromycin- and amoxicillin/clavulanate-treated patients, respectively, demonstrated clinical cure (as defined in 1998 draft US Food and Drug Administration guidelines); among clinically and bacteriologically evaluable patients, 92% versus 89%, respectively, demonstrated bacteriologic cure. Overall pathogen eradication rates were similar in the 2 groups (88% clarithromycin, 89% amoxicillin/clavulanate). Rates of premature discontinuation of study drug for any reason differed between treatments: 3% (4/142) of clarithromycin-treated patients versus 12% (17/145) of amoxicillin/clavulanate-treated patients (P = 0.005). One percent (2/142) and 6% (8/145) of the respective treatment groups discontinued study drug because of adverse events. Adverse events generally occurred with a similar frequency in the 2 groups; however, taste alteration was more common with clarithromycin (9/142 [6%]) than with amoxicillin/clavulanate (1/145 [1%]; P = 0.01). Mean severity scores for gastrointestinal adverse events showed a significant difference between groups (1.16 for clarithromycin-treated patients and 1.58 for amoxicillin/clavulanate-treated patients: P = 0.016). CONCLUSIONS: The results of this study demonstrate the clinical and bacteriologic equivalence and improved gastrointestinal tolerability of a 7-day course of once-daily extended-release clarithromycin relative to a 10-day course of twice-daily amoxicillin/clavulanate in the treatment of AECB. PMID- 11219482 TI - Blood pressure control in patients with mild to moderate essential hypertension switched from nifedipine gastrointestinal therapeutic system (GITS) 30 mg to nifedipine GITS 20 mg. AB - BACKGROUND: Nifedipine gastrointestinal therapeutic system (GITS) is a once-daily formulation of nifedipine that provides sustained plasma nifedipine concentrations throughout the 24-hour dosing interval. OBJECTIVE: This study was undertaken to determine if adult patients with mild to moderate essential hypertension whose blood pressure had been controlled for > or = 3 months with nifedipine GITS 30 mg could be successfully switched to a 20-mg daily dose with continued antihypertensive efficacy. METHODS: This was a randomized, double blind, parallel-group study. Patients entered a 1-week run-in period during which they continued to receive their usual antihypertensive medication, including nifedipine GITS 30 mg. After baseline assessment, patients entered a 6-week treatment period during which they were randomly assigned to receive nifedipine GITS 30 or 20 mg. Men and women were eligible to participate if they were > or = 55 years of age, had received a diagnosis of mild to moderate essential hypertension (sitting diastolic blood pressure [DBP] 95-114 mm Hg), and had exhibited good blood pressure control (sitting DBP < or = 90 mm Hg) while taking nifedipine GITS 30 mg once daily for > or = 3 months. Systolic blood pressure (SBP), DBP, and heart rate were recorded at baseline and after 1, 3, and 6 weeks of treatment. Adverse events were reported by patients. The responder rate was defined as the percentage of patients whose sitting DBP was < 95 mm Hg at the final study assessment. Results were based on the intent-to-treat analyses, which included data for all patients who received > or = 1 dose and had 1 postbaseline blood pressure assessment. Statistical significance was set at P < 0.05. RESULTS: Seventy-five patients entered the 1-week run-in period; 71 patients (94.7%) were randomized to treatment. Twenty-four patients received nifedipine GITS 30 mg for 43.0 +/- 3.3 days, and 47 patients received nifedipine GITS 20 mg for 42.5 +/- 6.7 days. Both groups exhibited a sustained decrease in blood pressure throughout the study; minor variations were not statistically significant. End-point SBP and DBP for the 30- and 20-mg groups were 135.5 +/- 9.8/81.7 +/- 5.4 mm Hg and 138.6 +/- 11.8/82.9 +/- 7.6 mm Hg, respectively. Changes from baseline in end-point SBP and DBP did not differ significantly between groups. At the end of treatment, goal DBP (< 95 mm Hg) was achieved by 24 of 24 patients (100%) receiving the 30 mg dose and 45 of 47 patients (95.7%) receiving the 20-mg dose. Blood pressure control (sitting DBP < 90 mm Hg) was achieved by 21 of 24 (87.5%) patients in the 30-mg group and 35 of 47 (74.5%) patients in the 20-mg group. The most commonly reported adverse event was headache; 2 patients discontinued the study because of adverse events. Overall, 9 of 24 patients (37.5%) in the 30-mg group and 14 of 47 patients (29.8%) in the 20-mg group experienced > or = 1 treatment-related adverse event. CONCLUSIONS: Patients whose mild to moderate essential hypertension is controlled with nifedipine GITS 30 mg once daily may be able to switch to 20 mg once daily with continued antihypertensive efficacy. In addition to safety and economic advantages, such a switch may be a reasonable alternative in patients with lower body weight or as an adjunct to existing antihypertensive therapy. PMID- 11219483 TI - Comparison of 5-day, short-course gatifloxacin therapy with 7-day gatifloxacin therapy and 10-day clarithromycin therapy for acute exacerbation of chronic bronchitis. AB - BACKGROUND: The ideal duration of antibiotic therapy for acute exacerbation of chronic bronchitis (AECB) remains controversial. OBJECTIVE: This study compared short-course, 5-day gatifloxacin treatment with standard 10-day clarithromycin treatment in patients with AECB; 7-day gatifloxacin therapy was a secondary comparator. METHODS: This was a multicenter, prospective, randomized, double blind study in which adult outpatients with AECB were randomized to 1 of 3 treatment groups: 5 days of gatifloxacin, 7 days of gatifloxacin, or 10 days of clarithromycin. Clinical cure and microbiologic eradication rates were determined 7 to 14 days after the completion of antibiotic treatment. RESULTS: A total of 527 patients with AECB were enrolled and treated with study drug (174, gatifloxacin 5-day; 175, gatifloxacin 7-day; 178, clarithromycin 10-day). Most patients (82%) had type 1 (severe) exacerbations, and a bacterial pathogen was isolated from pretreatmer, sputum samples in 59% of patients. The overall clinical cure rates among clinically evaluable patients were comparable between groups: 89% (135/151 patients) in the gatifloxacin 5-day group; 88% (136/154) in the gatifloxacin 7-day group; and 89% (145/163) in the clarithromycin 10-day group. The 95% CIs for the differences in response rates were -6.1 to 7.0 for gatifloxacin 5-day versus clarithromycin, -8.9 to 5.0 for gatifloxacin 7-day versus clarithromycin, and -5.5 to 8.0 for gatifloxacin 5-day versus 7-day. These observations did not appear to be affected by use of corticosteroids or smoking status, type of exacerbation, or duration of current episode. The microbiologic eradication rate among microbiologically evaluable pathogens was >90% in all treatment groups. No clinically meaningful differences were noted in the incidence of drug-related adverse events. CONCLUSION: Short-course, 5-day gatifloxacin therapy in patients with AECB resulted in clinical cure and microbiologic eradication rates comparable to those of standard 7- and 10-day therapies. PMID- 11219484 TI - The role of the clinical pharmacologist in the management of adverse drug reactions. AB - The classical definition of clinical pharmacology is the study or the knowledge of the effects of drugs in humans. The activities of a clinical pharmacologist can vary from country to country, usually ranging from involvement in clinical trials, especially fundamental pharmacodynamic studies, to studies of pharmacokinetics and drug metabolism, to pharmacogenetics. Most clinical pharmacologists outside industry are in hospitals or university hospitals and research centres. In addition to research, this implies teaching of clinical pharmacology, and interacting with other medical staff: in the field of research, giving advice on clinical trials methodology and often managing a therapeutic drug monitoring centre. Some clinical pharmacologists have clinical departments with beds or consulting offices. Can there be another role for the clinical pharmacologist that would increase his or her usefulness for the medical community? Adverse drug reactions (ADRs) are remarkably complex events, related to drug effects, patient characteristics (background diseases, genetics), and drug/disease interactions. Evaluation of ADRs requires understanding of drug mechanisms and interactions, and of disease diagnostics, especially in the discussion of alternative diagnoses. This implies expertise as a pharmacologist and a clinician. In addition, because not all adverse reactions or interactions are in the Summary of Product Characteristics, and because problems arise long before they report in the literature, it is necessary for the clinical pharmacologist to have knowledge of ongoing regulatory processes, in addition to having access to the published literature. Helping clinicians cope with individual patient problems will also improve the clinical pharmacologist's integration into the healthcare process. PMID- 11219485 TI - Anticancer drug-induced kidney disorders. AB - Nephrotoxicity is an inherent adverse effect of certain anticancer drugs. Renal dysfunction can be categorised as prerenal uraemia, intrinsic damage or postrenal uraemia according to the underlying pathophysiological process. Renal hypoperfusion promulgates prerenal uraemia. Intrinsic renal damage results from prolonged hypoperfusion, exposure to exogenous or endogenous nephrotoxins, renotubular precipitation of xenobiotics or endogenous compounds, renovascular obstruction, glomerular disease, renal microvascular damage or disease, and tubulointerstitial damage or disease. Postrenal uraemia is a consequence of clinically significant urinary tract obstruction. Clinical signs of nephrotoxicity and methods used to assess renal function are discussed. Mechanisms of chemotherapy-induced renal dysfunction generally include damage to vasculature or structures of the kidneys, haemolytic uraemic syndrome and prerenal perfusion deficits. Patients with cancer are frequently at risk of renal impairment secondary to disease-related and iatrogenic causes. This article reviews the incidence, presentation, prevention and management of anticancer drug induced renal dysfunction. Dose-related nephrotoxicity subsequent to administration of certain chloroethylnitrosourea compounds (carmustine, semustine and streptozocin) is commonly heralded by increased serum creatinine levels, uraemia and proteinuria. Additional signs of streptozocin-induced nephrotoxicity include hypophosphataemia, hypokalaemia, hypouricaemia, renal tubular acidosis, glucosuria, aceturia and aminoaciduria. Cisplatin and carboplatin cause dose related renal dysfunction. In addition to increased serum creatinine levels and uraemia, electrolyte abnormalities, such as hypomagnesaemia and hypokalaemia, are commonly reported adverse effects. Rarely, cisplatin has been implicated as the underlying cause of haemolytic uraemic syndrome. Pharmaceutical antidotes to cisplatin-induced nephrotoxicity include amifostine, sodium thiosulfate and diethyldithiocarbamate. Dose- and age-related proximal tubular damage is an adverse effect of ifosfamide. In addition to renal wasting of electrolytes, glucose and amino acids, Fanconi syndrome, rickets and osteomalacia have occurred with ifosfamide treatment. High dose azacitidine causes renal dysfunction manifested by tubular acidosis, polyuria and increased urinary excretion of electrolytes, glucose and amino acids. Haemolytic uraemia is a rare adverse effect of gemcitabine. Methotrexate can cause increased serum creatinine levels, uraemia and haematuria. Acute renal failure is reported following administration of high dose methotrexate. Urinary alkalisation and hydration confer protection against methotrexate-induced renal dysfunction. Dose-related nephrotoxicity, including acute renal failure, are reported subsequent to treatment with pentostatin and diaziquone. Acute renal failure is a rare adverse effect of treatment with interferon-alpha. Haemolytic uraemic syndrome occurs with mitomycin administration. A mortality rate of 50 to 100% is reported in patients developing mitomycin-induced haemolytic uraemic syndrome. Capillary leak syndrome occurring with aldesleukin therapy can cause renal dysfunction. Infusion-related hypotension during infusion of high dose carmustine can precipitate renal dysfunction. PMID- 11219486 TI - Nephrotoxicity and hepatotoxicity of histamine H2 receptor antagonists. AB - The extensive use of selective histamine H2 receptor antagonists provides a unique opportunity to describe very rare adverse drug reactions. Although mild elevation of serum creatinine level following the administration of cimetidine is relatively common, acute interstitial nephritis (AIN) is a rare hypersensitivity reaction. There have been 25 published reports of AIN associated with H2 antagonist therapy and we also identified 16 cases from the Australian Adverse Drug Reaction Advisory Committee (ADRAC) database. AIN was reported most commonly following cimetidine administration. AIN was supported by renal biopsy in 28 patients and by rechallenge in 6. H2 antagonist-induced AIN was more commonly reported in men older than 50 years. In the majority of cases the onset was within 2 weeks of initiation of therapy (1 day to 11 months). The clinical manifestations were nonspecific including sterile pyuria, elevated erythrocyte sedimentation rate, fatigue, proteinuria and leucocytosis whereas rash, arthralgia and flank pain were rarely reported. There were 170 cases of hepatotoxicity following H2 antagonist administration reported to ADRAC. These were more common following ranitidine and included cholestatic, hepatocellular and mixed reactions. Hepatotoxicity was proven following liver biopsy in several cases published in the literature and in 15 cases reported to ADRAC. Hepatotoxicity recurred upon rechallenge in 6 cases. Generally, renal and hepatic adverse effects resolved quickly after cessation of H2 antagonist therapy and did not require specific treatment. Nephrotoxicity and hepatotoxicity following administration of an H2 antagonist is rare and a high index of suspicion is necessary for early detection. Now that many H2 antagonists are available over the counter, awareness of these conditions and early detection with cessation of H2 antagonist therapy would appear paramount. PMID- 11219489 TI - Potent antitumor effects of intra-arterial injection of fibroblasts genetically engineered to express IL-12 in liver metastasis model of rat: no additional benefit of using retroviral producer cell. AB - Interleukin-12 (IL-12) mediates significant antitumor effects in animal models but associated with dose-dependent toxicity in human. To achieve local expression of IL-12 at the tumor site without systemic toxicity, we performed intra-arterial administration of fibroblasts genetically engineered to produce IL-12 protein with or without retrovirus (CRIP- IL-12 or 3T3-IL-12) in liver metastasis model. Rat breast cancer cells ( MADB - 106) were injected into the portal vein of syngeneic Fisher rats on day 0, and fibroblasts were injected into the hepatic artery on day 7. On day 21, liver weight and number of liver tumors were examined. As controls, CRIP cells expressing retrovirus carrying lacZ marker gene (CRIP-lacZ) or saline (Hanks balanced salt solution, HBSS) were injected. Administration of CRIP-IL-12 significantly reduced tumor metastasis in liver measured by number of foci (CRIP- IL-12: 45.2 +/- 36.7, CRIP-lacZ: >250, HBSS: >250, P<.05) and by liver weight (CRIP-IL-12: 13.0+/-2.5 g, CRIP-lacZ: 30.4+/-8.5 g, HBSS: 26.0+/-7.6 g, P<.05). 3T3-IL-12, which produced only IL-12 protein but not IL-12 retrovirus, also had significant antitumor effects equivalent to CRIP IL-12. Intra-arterial injection of IL-12--producing fibroblasts into the liver may be an effective therapy for liver tumors reducing systemic toxicity, and could be developed for clinical application. PMID- 11219490 TI - Suppression of mammary carcinoma growth in vitro and in vivo by inducible expression of the Cdk inhibitor p21. AB - Mammary carcinomas that develop in C3 (1)/SV40 T- antigen (TAg) transgenic mice have lost the p53-mediated induction of p21, leading to increased cellular proliferation and significant elevations of cyclins and Cdks. To test whether p21 could serve as a target for anticancer therapy for this mammary cancer model, a retroviral delivery system for the inducible expression of p21 was developed. We demonstrate that overexpression of p21 in C3(1)/TAg mammary tumor cells using the retroviral inducible p21 expression system results in increased apoptosis, reduced cell proliferation in vitro and reduced tumor growth in vivo associated with reduced expression of cyclins D1 and E, and Cdks 2, 4, and 6. Reciprocal changes in the expression of p21 and p27(Kip1), another cell-cycle regulator, were also observed. Because reduced p21 expression occurs frequently in human breast cancer, restoration of the Cdk inhibitor p21 by gene therapy approaches may provide a method for inhibiting mammary tumor progression. PMID- 11219487 TI - Bodyweight gain with atypical antipsychotics. A comparative review. AB - The atypical antipsychotics have been shown to have superior efficacy compared with typical antipsychotics such as haloperidol, particularly in the treatment of negative symptoms of schizophrenia. Furthermore, they induce less extrapyramidal effects. However, following clinical use, marked bodyweight gain has been frequently observed with some of the atypical antipsychotic drugs. In order to examine and compare the frequency, amount and conditions of bodyweight gain during treatment with atypical antipsychotics, studies concerning bodyweight gain with these agents were identified through a MEDLINE search from 1966 to March 2000. Although comparison is limited by the different designs and recruitment procedures of the reviewed studies, the available data support the notion that the frequency as well as the amount of bodyweight gain is high in patients treated with olanzapine (average bodyweight gain 2.3 kg/month), clozapine (1.7 kg/month), quetiapine (1.8 kg/month), and possibly also zotepine (2.3 kg/month). Moderate changes in bodyweight have been observed in the treatment with risperidone (average bodyweight gain 1.0 kg/month). Ziprasidone seems to induce only slight bodyweight changes (0.8 kg/month). Bodyweight gain most frequently occurs in the first 12 weeks of treatment. Patients who were underweight at the beginning of treatment are at highest risk of gaining bodyweight. The underlying pathomechanism still remains largely unclear. The relative receptor affinities of the atypical antipsychotics for histamine H1 receptors as well as the ratio of their affinity for serotonin 5-HT2 and dopamine D2 receptors appear to be the most robust correlate of bodyweight gain. Furthermore, the induction of leptin secretion may have an important impact on bodyweight gain in patients treated with atypical antipsychotics. Although many questions concerning the pathogenesis of bodyweight gain remain unresolved, this adverse effect has to be taken into consideration when prescribing the atypical antipsychotics, particularly in view its affect on compliance during long term treatment and the long term effects of obesity on mortality and morbidity. PMID- 11219488 TI - NSAID-induced nephrotoxicity from the fetus to the child. AB - In this review we report data available from the literature on the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and the development of nephrotoxicity in the fetus, neonates and children. Up to the present day, several cases of severe and sometimes irreversible renal insufficiency have been described in neonates exposed to indomethacin prenatally or in the first days of life for treatment of patent ductus arteriosus (PDA). Until now, very few studies have been carried out on alternative treatments for PDA in preterm infants; ibuprofen has been shown to be as effective as indomethacin in closing the ductus in this patient group without affecting renal function. In children, NSAID induced renal failure is a rare event and is usually reversible after discontinuation of the drug. However, caution should be taken when NSAIDs are administered to individuals with preexisting renal problems or with other potentially nephrotoxic drugs. In these situations, new approaches such as cyclo oxygenase-2 selective inhibitors or prostanoid receptor selective antagonists could lead to alternative therapies for use in paediatrics. PMID- 11219491 TI - Substantially improved in vivo radiosensitization of rat glioma with mutant HSV TK and acyclovir. AB - We recently demonstrated in vitro that a mutant HSV-TK (mutant 75) expressed from an adenovirus (AdCMV-TK75) radiosensitized rat RT2 glioma cells significantly better than wild type HSV-TK (AdCMV-TK) in combination with acyclovir (ACV). To examine whether a similar improvement could also be observed in vivo, we tested these viruses in a syngeneic rat glioma tumor model (RT2/Fischer 344). First, we demonstrate that treatment with AdCMV-TK and ACV significantly radiosensitizes implanted gliomas and roughly doubles the mean survival time to 37 days, compared to 20 days for control animals implanted with Adbetagal-transduced cells (P<.02). Second, it was important to first examine the effect of AdCMV-TK75 and ACV on survival without any irradiation. We found that AdCMV-TK75 appeared to sensitize gliomas more efficiently than AdCMV-TK, although this difference was not significant ( P= .19 ). Third, and most importantly, in combined HSV-TK, ACV and irradiation experiments, we demonstrate that AdCMV-TK75 is superior over AdCMV-TK and significantly (P<.005) prolonged the survival of treated animals. Our results suggest that AdCMV-TK75 is far more efficient than AdCMV-TK in radiosensitizing rat glioma when administered in combination with ACV. PMID- 11219493 TI - Adenovirus-mediated delivery of antiangiogenic genes as an antitumor approach. AB - Based on the observation that the growth of solid tumors is dependent on the formation of new blood vessels, therapeutic strategies aimed at inhibiting angiogenesis have been proposed. A number of proteins with angiostatic activity have been described, but their development as therapeutic agents has been hampered by difficulties in their production and their poor pharmacokinetics. These limitations may be resolved using a gene therapy approach whereby the genes are delivered and expressed in vivo. Here we compared adenoviral delivery of endostatin, proliferin-related protein (PRP), and interferon-inducible protein 10 (IP10) genes. Recombinant adenoviruses carrying the three angiostatic genes express biologically active gene products as determined in vitro in endothelial cell proliferation and migration assays, and in vivo by inhibition of neoangiogenesis in rat chambers. Eradication of established tumors in vivo, in the murine B16F10 melanoma model in immunocompetent mice, was not achieved by intratumoral injection of the different vectors. However, the combination of intravenous plus intratumoral injections allowed rejection of tumors. Ad-PRP or Ad-IP10 were significantly more efficient than Ad-endostatin, leading to complete tumor rejection and prolonged survival in a high proportion of treated animals. These data support the use of in vivo gene delivery approaches to produce high circulating and local levels of antiangiogenic agents for the therapy of local and metastatic human tumors. PMID- 11219492 TI - Targeting the replication of adenovirus to p53-defective thyroid carcinoma with a p53-regulated Cre/loxP system. AB - In this article, we evaluated the feasibility of the restricted replication competent adenoviruses for treatment of anaplastic thyroid carcinomas (ATCs), which are very aggressive and difficult to treat. Because ATCs very often harbor p53 mutations, we used wt-p53 as a regulatory factor to restrict virus replication and cytopathic effect to p53-mutated cells. The recently reported "gene inactivation strategy" using p53-regulated Cre/loxP system was employed; this system consists of two recombinant adenoviruses. One has an expression unit of the synthetic p53 - responsive promoter and the Cre recombinase gene (Axyp53RECre), and another contains two expression units; the first consists of E1A gene flanked by a pair of loxP sites downstream of the constitutive CAG promoter and the second E1B19K gene under the control of the CMV promoter (AdCALE1AL). We expected that coinfection of these two adenoviruses into the cells with wt-p53 would lead to expression of the Cre, which excises E1A gene and switches off E1A expression resulting in no virus replication, whereas in the cells with mutant p53 E1A could be expressed that leads to virus replication and cell lysis. Our in vitro data demonstrate that although infection of AdCALE1AL alone led to E1A expression, viral replication and cytolysis in all the thyroid cells examined irrespective of their p53 status, the double infection did so in FRO cells (p53-null ATC) but not in FRO cells stably expressing wt-p53 and normal thyroid cells with wt-p53. These data indicate that our double infection method may have a potential for treatment of ATC and probably also other p53-defective cancer cells. PMID- 11219494 TI - Fusogenic activity of vesicular stomatitis virus glycoprotein plasmid in tumors as an enhancer of IL-12 gene therapy. AB - We have characterized the fusogenic activity of a plasmid expression system encoding vesicular stomatitis virus G protein (VSVG) in vitro and in vivo. Over 70% of murine colon and renal carcinoma cells (MC38 and Renca, respectively) transfected with VSVG plasmid in vitro fused and formed polykaryons upon incubation with pH 5.5 media. Using a plasmid expression system encoding VSVG and bacterial green fluorescent protein (GFP) formulated in a polyvinyl pyrrolidone (PVP) delivery system, diffusion of GFP throughout the VSVG-induced syncytia was shown in vivo in MC38 and Renca tumors. Moreover, tumor-bearing mice showed tumor growth inhibition following in vivo transfection with VSVG plasmid at an optimal dose of 48 microg. We have previously shown that direct injection of interleukin 12 (IL -12) plasmid complexed with PVP into tumors induces a strong immune response. In the current study, we assessed the ability of VSVG to elicit an antitumor response by enhancing cytokine gene delivery within the tumor mass. Tumor-bearing mice treated intratumorally with both VSVG/PVP and IL-12/PVP (48 and 24 microg, respectively) showed increase in tumor rejection when compared to IL- 12 plasmid alone (75% vs. 50%, respectively). These data suggest that VSVG gene therapy can be used in combination with other therapeutic genes to induce an antitumor response in vivo by enhancing the expression of the gene of interest. PMID- 11219495 TI - Antitumor activity of recombinant adenoviral vectors expressing murine IFN-alpha in mice injected with metastatic IFN-resistant tumor cells. AB - Recent studies have shown that gene therapy with type I interferon (IFN) in an adenovirus vector is a powerful tool to suppress the growth of human tumors transplanted in immune-deficient mice. However, in these studies the host immune mediated effects, which may be important in mediating the long-term control of tumor growth by these cytokines, was not studied. In this paper, we evaluate the antitumor efficacy of different adenoviral vectors containing mouse IFN-alpha genes (i.e., a first-generation replication-defective vector containing IFN alpha1 and two different second-generation vectors containing IFN-alpha2) in immunocompetent DBA/2 mice transplanted with highly metastatic Friend leukemic cells resistant in vitro to type I IFN. We found that injection of all the different adenovirus vectors containing mouse IFN-alpha( genes resulted in a marked antitumor response in mice transplanted either subcutaneously or intravenously with IFN-resistant Friend leukemic cells compared to tumor-bearing animals inoculated with a control vector. Tumor growth inhibition after injection of IFN-adenovirus vectors was associated with a prolonged presence of high IFN levels in the sera of the injected mice. Suppression of metastatic tumor growth was also observed after a single injection of the IFN--adenovirus recombinant vectors, whereas a comparable antitumor response generally required several injections of high doses of IFN. Altogether, these results demonstrate that IFN- adenoviral vectors can efficiently inhibit metastatic tumor growth by host mediated mechanisms and suggest that adenovirus-mediated IFN-alpha gene therapy may represent an attractive alternative to the conventional clinical use of this cytokine, which generally requires multiple injections of high IFN doses for a prolonged period of time. PMID- 11219496 TI - Postoperative immuno-gene therapy of murine bladder tumor by in vivo administration of retroviruses expressing mouse interferon-gamma. AB - The murine MBT-2 bladder tumor model in syngeneic C3H/HeN mice was used to investigate the feasibility of gene therapy based on the delivery of interferon gamma (IFN-gamma) in vivo by retroviral vectors. We constructed a recombinant retroviral vector pRUFneo/IFN-gamma, which was transfected into a retroviral packaging cell line psiCRE, to produce psiCRE/pRUFneo/IFN-gamma cells. The expressions of the neo and IFN-gamma genes were verified by reverse transcription polymerase chain reaction and IFN-gamma was detected in the culture supernatant from psiCRE/pRUFneo/IFN-gamma cells. After receiving MBT-2 cells admixed with retroviral pRUFneoIFN-gamma supernatant, C3H/HeN mice exhibited lower tumor incidence, lower tumor mass, and higher survival rate, as well as higher antitumor responses compared to those injected with MBT-2 cells admixed with control retroviral supernatant. Moreover, the retroviral pRUFneoIFN-gamma supernatant was able to suppress the growth of rechallenged tumors in postoperated mice. Although the IFN-gamma protein secreted from psiCRE/pRUFneo/IFN-gamma cells partly contributes to the antitumor effect of retroviral pRUFneoIFN-gamma supernatant, the retroviruses carrying the IFN-gamma gene transduced MBT-2 cells in vivo, which may result in enhancing local IFN gamma production from tumor cells. Because bladder is suitable for the intravesical instillation of therapeutic agents, in vivo administration of retroviral vectors encoding IFN-gamma may be explored for the treatment of bladder cancer. PMID- 11219497 TI - Successful immunogene therapy using colon cancer cells (colon 26) transfected with plasmid vector containing mature interleukin-18 cDNA and the Igkappa leader sequence. AB - IL-18 is a novel cytokine that induces interferon (IFN)-gamma secretion and plays an important role in antitumor immunity. In the present study, we constructed plasmid vectors encoding the murine mature IL-18 cDNA linked with the Igkappa leader sequence and the pro-IL-18 cDNA to estimate the efficacy of the mature IL- 18 vector and to evaluate IL-18--producing tumor cells as a tumor vaccine. Colon 26 cells were transfected with the abovementioned vectors or with vector alone (mock). Reverse transcription-polymerase chain reaction analysis showed increased expression of murine IL-18 cDNA in both mature IL-18 and pro-IL-18 transfectants in comparison to that in mock transfected cells. The ability of the culture supernatants of mature IL-18 transfectants to induce IFN-gamma secretion was extremely high (40-140 pg/10(6) cells) in comparison to that of pro-IL-18 transfectants (4-18 pg/10(6) cells). When injected into syngeneic BALB/c mice, the growth of mature IL-18 transfectants, but not pro-IL-18 transfectants, was significantly less than that in mock transfected cells ( P< .01, by ANOVA and analysis of covariance). In addition, injection of colon 26 or Meth-A cells into mice immunized with a mature IL-18 transfectant revealed acquired immunity. Depletion of natural killer cells did not affect the growth of transfectants. However, the growth inhibitory effects were partially abrogated following treatment with anti-CD4+ and anti-CD8+ antibodies. These data suggest that the rejection of mature IL-18/colon 26 cells was mediated through T-cell activation. Gene therapy using mature IL-18 transfectants containing a plasmid vector and the Igkappa leader sequence may be a useful tumor vaccine. PMID- 11219498 TI - The relationship between aerobic fitness and recovery from high intensity intermittent exercise. AB - A strong relationship between aerobic fitness and the aerobic response to repeated bouts of high intensity exercise has been established, suggesting that aerobic fitness is important in determining the magnitude of the oxidative response. The elevation of exercise oxygen consumption (VO2) is at least partially responsible for the larger fast component of excess post-exercise oxygen consumption (EPOC) seen in endurance-trained athletes following intense intermittent exercise. Replenishment of phosphocreatine (PCr) has been linked to both fast EPOC and power recovery in repeated efforts. Although 31P magnetic resonance spectroscopy studies appear to support a relationship between endurance training and PCr recovery following both submaximal work and repeated bouts of moderate intensity exercise, PCr resynthesis following single bouts of high intensity effort does not always correlate well with maximal oxygen consumption (VO2max). It appears that intense exercise involving larger muscle mass displays a stronger relationship between VO2max and PCr resynthesis than does intense exercise utilising small muscle mass. A strong relationship between power recovery and endurance fitness, as measured by the percentage VO2max corresponding to a blood lactate concentration of 4 mmol/L, has been demonstrated. The results from most studies examining power recovery and VO2max seem to suggest that endurance training and/or a higher VO2max results in superior power recovery across repeated bouts of high intensity intermittent exercise. Some studies have supported an association between aerobic fitness and lactate removal following high intensity exercise, whereas others have failed to confirm an association. Unfortunately, all studies have relied on measurements of blood lactate to reflect muscle lactate clearance, and different mathematical methods have been used for assessing blood lactate clearance, which may compromise conclusions on lactate removal. In summary, the literature suggests that aerobic fitness enhances recovery from high intensity intermittent exercise through increased aerobic response, improved lactate removal and enhanced PCr regeneration. PMID- 11219500 TI - Physiological and cardiovascular changes associated with deep water running in the young. Possible implications for the elderly. AB - The increased number of people taking part in deep water running (DWR) is attributable to the weight-independent characteristic of this form of exercise. Deep water runners should, however, be aware of the respiratory and cardiovascular repercussions that result from exercising in water. It has been well documented that water immersion (WI) alone results in decrements in respiratory and cardiovascular parameters in young individuals immersed in water to the neck. These decrements become more pronounced with exercise, such that maximal oxygen consumption and heart rate (HR) are lower during DWR compared with running on land. Age also seems to influence these parameters; Derion et al. found little to no change in cardiac output, stroke volume and HR during WI in older individuals compared with the decrease experienced in younger individuals. In contrast, gender appears to have no effect on WI or DWR response. Although differences in acute metabolic responses have been observed in numerous studies, training studies examining the effectiveness of using a DWR training programme found that DWR produced equivocal training responses when compared with fit and highly trained individuals running on land. Less convincing evidence has been provided for untrained individuals seeking benefits from a DWR training programme, as some studies showed significant improvements while others did not. There is a current lack of knowledge regarding the use of this form of exercise by frail elderly individuals and/or those with osteoporosis. PMID- 11219499 TI - Interval training for performance: a scientific and empirical practice. Special recommendations for middle- and long-distance running. Part I: aerobic interval training. AB - This article traces the history of scientific and empirical interval training. Scientific research has shed some light on the choice of intensity, work duration and rest periods in so-called 'interval training'. Interval training involves repeated short to long bouts of rather high intensity exercise (equal or superior to maximal lactate steady-state velocity) interspersed with recovery periods (light exercise or rest). Interval training was first described by Reindell and Roskamm and was popularised in the 1950s by the Olympic champion, Emil Zatopek. Since then middle- and long- distance runners have used this technique to train at velocities close to their own specific competition velocity. In fact, trainers have used specific velocities from 800 to 5000m to calibrate interval training without taking into account physiological markers. However, outside of the competition season it seems better to refer to the velocities associated with particular physiological responses in the range from maximal lactate steady state to the absolute maximal velocity. The range of velocities used in a race must be taken into consideration, since even world records are not run at a constant pace. PMID- 11219503 TI - Controlled cell deformation produces defined areas of contact between cells and ligand-coated surfaces. AB - A method which allows precise control of the time of initiation and the area of contact of T cells with immobilized ligands has been developed. Cells are trapped in an asymmetric film that can be quantitatively thinned by reducing the film's capillary pressure. Ligands adsorbed to the base of the apparatus are forced into close contact with the cells as the air-liquid interface is drawn down. Using interference microscopy and microbeads to indicate the film height, the amount of thinning can be controlled to within 1 microm. In this study, this system was used to produce contact areas of 182 and 356 microm2 between T cells and anti-CD3 coated surfaces. These contact areas were measured using fluorescent dye exclusion microscopy. This apparatus can be used for quantitative studies of T cell activation, as is reported in Patrick et al., J. Immunol. Method. 24:97-108, 2000. PMID- 11219501 TI - Alterations in energy metabolism during exercise and heat stress. AB - Much of the research that has examined the interaction between metabolism and exercise has been conducted in comfortable ambient conditions. It is clear, however, that environmental temperature, particularly extreme heat, is a major practical issue one must consider when examining muscle energy metabolism. When exercise is conducted in very high ambient temperatures, the gradient for heat dissipation is significantly reduced which results in changes to thermoregulatory mechanisms designed to promote body heat loss. This can ultimately impact upon hormonal and metabolic responses to exercise which act to alter substrate utilisation. In general, the literature examining metabolic responses to exercise and heat stress has demonstrated a shift towards increased carbohydrate use and decreased fat use. Although glucose production appears to be augmented during exercise in the heat, glucose disposal and utilisation appears to be unaltered. In contrast, glycogen use has been consistently demonstrated to be augmented during exercise in the heat. This increase in glycogenolysis is observed via both aerobic and anaerobic pathways. Although several hypotheses have been proposed as mechanisms for the substrate shift towards greater carbohydrate metabolism during exercise and heat stress, recent work suggests that an augmented sympatho-adrenal response and intramuscular temperature may be responsible for such a phenomenon. PMID- 11219504 TI - A parametric approach to measuring cerebral blood flow autoregulation from spontaneous variations in blood pressure. AB - Autoregulation maintains cerebral blood flow (CBF) almost constant in the face of changes in arterial blood pressure (ABP). Tests for impairment of this process using only spontaneous fluctuations in ABP, without provoking large variations, are of great clinical interest, and a range of different approaches have previously been applied. Extending earlier work based on linear filters, we propose a simple parametric method using a first order finite impulse response filter. We evaluate the method on ABP and CBF velocity [(CBFV), from trancranial Doppler ultrasound] signals collected in 60 patients with stenosis or occlusion of the carotid arteries. Data were collected during the inspiration of ambient air, a 5% CO2/air mixture, and finally the return to ambient air. Equivalent data were collected in 15 normal subjects. The filters estimated from the data segments with constant inspiratory pCO2 showed the expected high-pass characteristic, which was reduced during hypercapnia and also in patients. Highly significant correlation between the filter parameters and cerebrovascular reactivity (percent increase in CBFV per unit change in end-tidal pCO2) gives further evidence that the filters reflect autoregulation. The method allows simple parametrization of the dynamic autoregulatory responses in CBFV, and the analysis of short (1 min) data segments. PMID- 11219502 TI - Fast pitch softball injuries. AB - The popularity of fast pitch softball in the US and throughout the world is well documented. Along with this popularity, there has been a concomitant increase in the number of injuries. Nearly 52% of cases qualify as major disabling injuries requiring 3 weeks or more of treatment and 2% require surgery. Interestingly, 75% of injuries occur during away games and approximately 31% of traumas occur during nonpositional and conditioning drills. Injuries range from contusions and tendinitis to ligamentous disorders and fractures. Although head and neck traumas account for 4 to 12% of cases, upper extremity traumas account for 23 to 47% of all injuries and up to 19% of cases involve the knee. Approximately 34 to 42% of injuries occur when the athlete collides with another individual or object. Other factors involved include the quality of playing surface, athlete's age and experience level, and the excessive physical demands associated with the sport. Nearly 24% of injuries involve base running and are due to poor judgement, sliding technique, current stationary base design, unorthodox joint and extremity position during ground impact and catching of cleats. The increasing prevalence of overtraining syndrome among athletes has been attributed to an unclear definition of an optimal training zone, poor communication between player and coach, and the limited ability of bone and connective tissue to quickly respond to match the demands of the sport. This has led routinely to arm, shoulder and lumbar instability, chronic nonsteroidal anti-inflammatory drug (NSAID) use and time loss injuries in 45% of pitching staff during a single season. Specific attention to a safer playing environment, coaching and player education, and sport-specific training and conditioning would reduce the risk, rate and severity of fast pitch traumas. Padding of walls, backstops, rails and dugout areas, as well as minimising use of indoor facilities, is suggested to decrease the number of collision injuries. Coaches should be cognisant of overtraining, vary day-to day training routines to decrease repetitive musculoskeletal stress, focus on motor skills with equal emphasis on speed and efficiency of movement, and use drills that reinforce sport-specific, decision making processes to minimise mental mistakes. Conditioning programs that emphasise a combination of power, acceleration, flexibility, technical skill, functional capacity and injury prevention are recommended. Due to the limited body of knowledge presently available on this sport, a greater focus on injury surveillance would provide a clearer picture of injury causation and effective management procedures, leading toward safer participation and successful player development. PMID- 11219505 TI - Short-Term biomechanical adaptation of the rat carotid to acute hypertension: contribution of smooth muscle. AB - The biomechanical adaptation of the arterial wall to hypertension has been studied extensively in recent years; however, the exact biomechanical contribution of vascular smooth muscle cells (VSMCs) during the adaptation process in conduit vessels is not known. We induced hypertension in 8 wk old Wistar rats by total ligation of the aorta between the two kidneys. Mean blood pressure increased from 92 +/- 2 (mean +/- SE) mm Hg to approximately 150 mmHg. Rats were sacrificed 2, 4, and 8 d after surgery and the left common carotid artery was excised for analysis. Wall thickness increased by 18% in 8 d and the opening angle by 32% in 4 d. The elastic properties were measured under normal VSMC tone (i.e., the amount of VSMC tone under normal conditions also called basal VSMC tone or normal resting VSMC tone), under maximally contracted VSMC (NE, 5 x 10(-7) mol/L) and under totally relaxed VSMC conditions (papaverine, 10( 4) mol/L). The most pronounced modifications were the changes in elastic properties related to normal VSMC tone. The functional contraction ratio at 100 mm Hg, defined as the relative contraction under normal conditions (normal VSMC tone), increased by 439% 4 d after the induction of hypertension. The total contraction capacity of the VSMC increased by 38% within 8 d. The changes in normal VSMC tone led to important changes in the mechanical properties of the arterial wall. Under normal VSMC conditions, compliance at mean pressure (148 mm Hg) increased by 159% within 8 d, whereas in the absence of VSMC tone, compliance did not increase significantly. We conclude that in conduit vessels, the VSMC, which is the sensing and effecting element of the adaptation process, is subjected to large-scale changes during the early phase of arterial adaptation to acute hypertension. PMID- 11219506 TI - Wave front-obstacle interactions in cardiac tissue: a computational study. AB - An understanding of wave front-obstacle interactions will greatly enhance our knowledge of the mechanisms involved in cardiac arrhythmias and their therapy. The goal of this computational study is to examine the interactions between wave fronts and various obstacles in a two-dimensional sheet of myocardium. The myocardium is modeled as an isotropic sheet with Luo-Rudy I membrane kinetics. An examination is conducted of wave front interactions with nonconductive and passive-tissue obstacles. Simulations were performed either in environments of reduced myocardial excitability, or with rapid stimulation via a line electrode. The shape of the obstacles and their ability to withdraw current from the active tissue greatly influence wave front-obstacle interactions in each of these environments. The likelihood of wave front detachment from an obstacle corner increases as the curvature of the obstacle corner is increased. A passive-tissue obstacle promotes wave front-obstacle separation in regions of depressed excitability. Under rapid pacing, the presence of the passive obstacle results in wave fragmentation, while the insulator obstacle promotes wave front detachment. The results of this study reveal the importance of obstacle composition and geometry in wave front interactions with cardiac obstacles. PMID- 11219507 TI - An experimentalist's approach to accurate localization of phase singularities during reentry. AB - A phase variable that uniquely represents the time course of the action potential has been used to study the mechanisms of cardiac fibrillation. A spatial phase singularity (PS) occurs during reentrant wave propagation and represents the organizing center of the rotating wave. Here, we present an error analysis to investigate how well PSs can be localized. Computer simulations of rotating spiral waves scaled appropriately for cardiac tissue were studied with various levels of noise added. The accuracy in identifying and localizing singularities depended on three factors: (i) the point chosen as the origin in state space used to calculate the phase variable; (ii) signal to noise ratio; and (iii) discretization (number of levels used to represent data). We found that for both simulation as well as experimental data, there existed a wide range for the choice of origin for which PSs could be identified. Discretization coupled with noise affected this range adversely. However, there always existed a range for choice of the origin that was 20% or more of the action potential amplitude within which the accuracy of localizing PSs was better than 2 mm. Thus, a precise determination of origin was not necessary for accurately identifying PSs. PMID- 11219508 TI - Compartmental analysis of breathing in the supine and prone positions by optoelectronic plethysmography. AB - Optoelectronic plethysmography (OEP) has been shown to be a reliable method for the analysis of chest wall kinematics partitioned into pulmonary rib cage, abdominal rib cage, abdomen, and right and left side in the seated and erect positions. In this paper, we extended the applicability of this method to the supine and prone positions, typically adopted in critically ill patients. For this purpose we have first developed proper geometrical and mathematical models of the chest wall which are able to provide consistent and reliable estimations of total and compartmental volume variations in these positions suitable for clinical settings. Then we compared chest wall (CW) volume changes computed from OEP(deltaVCW) with lung volume changes measured with a water seal spirometer (SP) (deltaVSP) in 10 normal subjects during quiet (QB) and deep (DB) breathing on rigid and soft supports. We found that on a rigid support the average differences between deltaVSP and deltaVCW were -4.2% +/- 6.2%, -3.0% +/- 6.1%, -1.7% +/- 7.0%, and -4.5% +/- 9.8%, respectively, during supine/QB, supine/DB, prone/QB, and prone/DB. On the soft surface we obtained -0.1% +/- 6.0%, -1.8% +/- 7.8%, 18.0% +/- 11.7%, and 10.2% +/- 9.6%, respectively. On rigid support and QB, the abdominal compartment contributed most of the deltaVCW in the supine (63.1% +/- 11.4%) and prone (53.5% +/- 13.1%) positions. deltaVCW was equally distributed between right and left sides. In the prone position we found a different chest wall volume distribution between pulmonary and abdominal rib cage (22.1% +/- 8.6% and 24.4% +/- 6.8%, respectively) compared with the supine position (23.3% +/- 9.3% and 13.6% +/- 13.0%). PMID- 11219510 TI - Potential of the genetic algorithm neural network in the assessment of gait patterns in ankle arthrodesis. AB - The aim of this study was to develop an empirical model of parameter-based gait data, based on an artificial neural network and a genetic algorithm, for the assessment of patients after ankle arthrodesis. Ground reaction force vectors were measured by force platforms during level walking. Nine force parameters expressed in percentage of body weight and their chronologic incidence of occurrence expressed in percentage of stance phase period were used in modeling. Ten healthy persons and ten patients who had solid arthrodesis of the ankle were recruited in this study for developing the model. By applying the genetic algorithm neural network, the percentage of correct classification was 98.8% and the subset of discriminant parameters was be reduced to 9 out of 18. These key parameters were mainly related to the loading response and propulsive phase. This indicates that there was a reduction in the abilities in cushion impact and push off in the patients after ankle arthrodesis. Finally, the relative distance (Dr) was defined in this study and used in two new patients' examinations to demonstrate its clinical utility. PMID- 11219509 TI - Transfer impedance of the respiratory system by forced oscillation technique and optoelectronic plethysmography. AB - To estimate the transfer impedance of the respiratory system (Ztr), we applied pressure forcing at the mouth from 1 to 24 Hz in eight healthy subjects and used optoelectronic plethysmography (OEP) to measure volume changes of the chest wall and its different compartments: pulmonary rib cage (RCp), abdominal rib cage (RCa) and abdomen (AB). Spectral analysis allowed assessment of input impedance (Zin) and total (Ztr) and compartmental (ZRCP, ZRCa, and ZAB) transfer impedances. As expected, averaged values of Zin and Ztr were similar at low frequencies (< 8 Hz) while they progressively differed at high frequencies. The percentage contributions of ZRCp, ZRCa , and ZAB to Ztr were, respectively, 35.3 +/- 1.4SD, 13.8 +/- 1.4, and 50.8 +/- 2.8 at low frequencies (< 8 Hz) and 63.1 +/ 5.5, 20.7 +/- 5.2, and 16.2 +/- 2.3 at higher frequencies (> 10 Hz). The validation of our approach was based on the comparison with a physical model comprised of a rubber membrane stretched over and attached to the lip of a bowl. We conclude that the combination of forced oscillations with OEP provides the simultaneous assessment of Zin and Ztr, it does not require the use of a plethysmographic chamber and it allows the separation between the different rib cage-abdominal pathways. PMID- 11219512 TI - A new algorithm for autoregression moving average model parameter estimation using group method of data handling. AB - A new algorithm for autoregresive moving average (ARMA) parameter estimation is introduced. The algorithm is based on the group method of data handling (GMDH) first introduced by the Russian cyberneticist, A. G. Ivakhnenko, for solving high order regression polynomials. The GMDH is heuristic in nature and self-organizes into a model of optimal complexity without any a priori knowledge about the system's inner workings. We modified the GMDH algorithm to solve for ARMA model parameters. Computer simulations have been performed to examine the efficacy of the GMDH and comparison of the GMDH is made to one of the most accurate and one of the most widely used algorithms, the fast orthogonal search (FOS) and the least-squares methods, respectively. The results show that in some cases with noise contamination and incorrect model order assumptions, the GMDH performs better than either the FOS or the least-squares methods in providing only the parameters that are associated with the true model terms. PMID- 11219511 TI - On the use of optical flow methods with spin-tagging magnetic resonance imaging. AB - Magnetic resonance imaging (MRI) is a versatile noninvasive tool for achieving full-field quantitative visualization of biomedical fluid flows. In this study, two MRI velocimetry techniques (spin tagging and phase contrast) are used to obtain velocity measurements in a Poiseuille flow for Reynolds numbers below 1,000. Spin-tagging MRI velocimetry supplies the displacement of tagged grids of nuclear spins from which the velocity field can be inferred, while phase contrast MRI velocimetry directly provides velocity data for every pixel in the field of view. Although the phase contrast method is more accurate for this flow, this technique is more sensitive to errors from magnetic susceptibility gradients, higher order motions, and has limited dynamic range. Spin-tagging MRI velocimetry is a viable alternative if automatic methods for extracting velocity fields from the tags can be found. Optical flow, a technique originally developed for machine vision applications, is proposed here as a postprocessing step to obtain two dimensional velocity fields from spin-tagging MRI images. Results with artificially generated grids demonstrate the robustness of the optical flow algorithm to noise and indicate that a 7%-10% average error can be expected from the optical flow calculations alone, independent of MRI image artifacts. Experiments on spin-tagging MRI images for a Re=230 Poiseuille flow gave an average error of 6.41%, which was consistent with the measurement error of the generated (synthetic) images with the same level of random noise superimposed. PMID- 11219513 TI - Twenty-year report of the first auditory brain stem nucleus implant. AB - We present the 20-year case report of an auditory implant placed on the dorsal cochlear nucleus with long-term electrical stimulation in a patient with neurofibromatosis 2. The patient has continued to use her implant daily for 20 years, and it has greatly enhanced her quality of life. There have been no adverse sequelae. PMID- 11219514 TI - Hearing improvement after therapy for hyperlipidemia in patients with chronic phase sudden deafness. AB - Hearing in patients with chronic-phase sudden deafness and associated hyperlipidemia tends to improve with therapy for hyperlipidemia. We studied 12 patients with unilateral sudden deafness and hyperlipidemia in whom more than 1 month had elapsed since the onset of the hearing disturbance. The disturbance was considered to be irreversible without therapy. The 4 men and 8 women ranged in age from 32 to 73 years, with a mean age of 54.3 years. The hearing disturbance was evaluated by measuring the air conduction thresholds at 125 to 8,000 Hz with pure tone audiometry. Hyperlipidemia was diagnosed when the total blood cholesterol level was 230 mg/dL or greater. The therapy for hyperlipidemia consisted of diet therapy and the administration of antilipemic agents. The hearing level was measured both before therapy and when the total blood cholesterol level had decreased to less than 230 mg/dL. After therapy, the mean hearing level had improved significantly (Wilcoxon's test, p < .05) at each of 125, 250, 500, and 2,000 Hz, but the changes in the level were not significant at 1,000, 4,000, or 8,000 Hz. Our results suggest that with therapy for hyperlipidemia, hearing tends to improve in patients with chronic-phase sudden deafness and associated hyperlipidemia, even when more than 1 month has elapsed since the onset of the presumably otherwise-irreversible hearing disturbance. PMID- 11219515 TI - Effects of exposing the opened endolymphatic sac to large doses of steroids to treat intractable Meniere's disease. AB - To enhance the effect of treatment for intractable Meniere's disease, we exposed the opened endolymphatic sac to high concentrations of steroids. This technique- endolymphatic sac drainage and steroid instillation surgery--involves the application of a mass of prednisolone followed by absorbable gelatin sponges soaked in a high concentration of dexamethasone into a sac lumen opened and expanded with a bundle of absorbable gelatin film. These sponges are also placed around the sac and coated with biochemical adhesive so that the medicine is slowly delivered into the sac over a prolonged period of time by means of a natural sustained-release vehicle. The short-term results (6 to 14 months) in 12 patients with Meniere's disease, including those in stage IV, treated by the above techniques showed that definitive spells were completely controlled in all cases. Hearing was improved, and annoyance due to tinnitus was decreased in all cases except one. PMID- 11219516 TI - Inner ear fluid volumes and the resolving power of magnetic resonance imaging: can it differentiate endolymphatic structures? AB - Magnetic resonance imaging (MRI) can accurately recognize minute volumes as small as 1 mm3. The volumes of the utricle and saccule of the inner ear are within the resolving power of MRI, but these structures cannot be recognized because the endolymph and perilymph signals are identical. To clarify the interpretation and description of inner ear structures on MRI, we measured and calculated the volumes of the perilymphatic and endolymphatic spaces of the human ear. We found the total volume of the bony labyrinth to be approximately 192.5 mm3 (endolymph, 34.0 mm3; perilymph, 158.5 mm3). PMID- 11219517 TI - Poly(adenosine diphosphate-ribose) synthetase inhibitor 3-aminobenzamide alleviates cochlear dysfunction induced by transient ischemia. AB - The present study was undertaken to determine the possible deleterious role played by poly(adenosine diphosphate-ribose) synthetase (PARS) in cochlear ischemia-reperfusion injury. Transient ischemia of the cochlea was induced in albino guinea pigs for 15, 30, or 60 minutes by pressing the labyrinthine artery at the porus acusticus internus. The animals were given intravenous 3 aminobenzamide (a PARS inhibitor) or physiological saline solution I minute before the onset of reperfusion. The compound action potential thresholds were measured before the onset of ischemia and 4 hours after the onset of reperfusion. A statistically significant reduction in the postischemic compound action potential threshold shift was observed in the animals treated with 3 aminobenzamide after 15 or 30 minutes of ischemia, whereas no statistical difference was found after 60 minutes of ischemia. These results suggest that excessive activation of PARS exerts deleterious effects on the cochlear injury induced by transient ischemia. PMID- 11219518 TI - Changes in permeability of strial vessels following vibration given to auditory ossicle by drill. AB - We produced drill-induced damage of the auditory ossicles of guinea pigs to study changes over time in the permeability of the blood vessels of the stria vascularis to horseradish peroxidase (HRP). In group A, the stimulus was applied for 10 seconds after intravenous injection of HRP. In group B, it was applied for 30 seconds, and in group C, for 60 seconds. The cochlea was fixed with 2% glutaraldehyde perfused through the round window, and the guinea pigs were then decapitated. The stria vascularis of the basal and third turns was examined. The leakage of HRP from the blood vessels of the stria vascularis significantly increased in relation to the duration of the stimulus in both the basal and third turns. The damage to intermediate cells also tended to be in relation to the duration of the stimulus. Extravascular permeation of HRP took place through the tubules in the endothelial cytoplasm. The vibratory stimulation presumably opened channels that are not normally open. PMID- 11219519 TI - Vestibular findings in professional divers. AB - The purpose of the present study was to investigate possible inner ear changes related to professional diving, by the documentation of auditory and vestibular function in 13 asymptomatic professional divers and 12 nondiver controls. A higher average pure tone hearing threshold, although of no clinical significance, was found in the study group (8.53 +/- 4.85 versus 6.67 +/- 3.54 dB hearing level, p = .04). In the vestibular evaluation, the smooth harmonic acceleration test phase leads for 0.01, 0.02, and 0.04 Hz were significantly lower in the divers (0.01 Hz, 38.46 degrees +/- 7.15 degrees versus 45.83 degrees +/- 9.02 degrees, p = .02; 0.02 Hz, 21.08 degrees +/- 5.19 +/- versus 25.17 degrees +/- 5.78 degrees, p = .05: 0.04 Hz, 12.38 degrees +/- 3.69 degrees versus 14.25 degrees +/- 3.14 degrees, p = .05). We suggest that the lower smooth harmonic acceleration phase values found in the professional divers, reflecting longer vestibulo-ocular reflex primary time constants and enhancement of the velocity storage mechanism, are the result of a habituation process that augments the low frequency response of the canal-ocular system. PMID- 11219520 TI - Immortalization of rat middle ear epithelial cells by adeno 12-SV40 hybrid virus. AB - Rat middle ear epithelial cells were infected with the adeno 12-SV40 hybrid virus. The cell line thus obtained displays features of primary cultured epithelial cells in both light microscopic and ultrastructural examinations. The immortalized cells have been in continuous proliferation for 40 passages and more than 17 months. Immunohistochemical analysis of the immortalized cells was positive for the SV40 T antigen and the tumor suppressor protein p53. The cells also stained positive for cytokeratin, an epithelial cell marker, and negative for vimentin, a fibroblast marker. These results, together with karyotype analysis, indicate that this cell line originated from rat middle ear epithelial cells and retains the characteristics of epithelial cells. This cell line will be useful for studying the normal cellular biology of middle ear epithelial cells, as well as the cellular and molecular mechanisms involved in the bacteria-middle ear epithelial cell interaction. PMID- 11219521 TI - Long-term study of endonasal duraplasty and review of the literature. AB - Many different techniques have been proposed to repair frontobasal dura mater lesions. Because of its low morbidity and high success rate, the endonasal approach has become a preferred route for treating cerebrospinal fluid fistulas of the anterior skull base. This article presents a retrospective evaluation of 136 endonasal duraplasties (126 patients) performed between July 1980 and May 1998 at a tertiary care facility. Follow-up consisted of clinical examinations including nasal endoscopy, objective measures, and telephone interviews. The following measures were used to evaluate the results of these duraplasties: postoperative nasal fluorescein endoscopy in 71 cases, computed tomographic cisternography in 2, nasal fluorescein endoscopy with computed tomographic cistemography in 19, magnetic resonance imaging in 6, and nasal fluorescein endoscopy with magnetic resonance imaging in 1. Tight closure was accomplished in 129 dural lesions (94.9%) on the first attempt. In 3 cases, recurrence of cerebrospinal fluid leakage was treated successfully by 1 endonasal revision, and in 1 case, a tight duraplasty was achieved after 2 endonasal revisions. Its high success rate, low rate of morbidity, and good long-term results recommend endonasal duraplasty as a primary treatment modality for frontobasal dural lesions. For extended frontobasal dural lesions, for which intracranial dural repair is the preferred approach, the endonasal approach should be used to close additional dural leaks of the sphenoid sinus. PMID- 11219522 TI - Correlation between microbiology and previous sinus surgery in patients with chronic maxillary sinusitis. AB - Aspirates of 108 chronically inflamed maxillary sinuses were processed for aerobic and anaerobic bacteria. There were 295 bacterial isolates: 109 aerobic and facultative, and 186 anaerobic. The predominant aerobic isolates were Staphylococcus aureus (17 isolates), alpha-hemolytic streptococci (14), Pseudomonas aeruginosa (12), Moraxella catarrhalis (10), and Haemophilus spp (8). The predominant anaerobes were Peptostreptococcus spp (61), Prevotella spp (45), Fusobacterium spp (15), and Propionibacterium acnes (14). Analysis of the medical histories revealed a correlation only between the microbial results and previous sinus surgery. Pseudomonas aeruginosa and gram-negative aerobic bacilli (GNAB) were more often isolated in patients who had surgery (9 of 33 patients had P aeruginosa and 17 had GNAB) than in patients who did not have surgery (3 of 75 had P aeruginosa and 7 had GNAB; p < .001). Anaerobes were isolated more often in patients who did not have surgery (69 of 75 patients) than in those who had previous surgery (21 of 33 patients; p < .001). These findings illustrate the unique microbiological features of chronic maxillary sinusitis that persist after sinus surgery. PMID- 11219523 TI - Loss of secondary esophageal peristalsis is not a contributory pathogenetic factor in posterior laryngitis. AB - Secondary esophageal peristalsis helps prevent the entry of gastric acid into the pharynx by clearing the refluxed gastric contents back into the stomach. Because the loss of this mechanism may contribute to the pathogenesis of reflux-induced laryngeal disorders, our aim was to study the frequency of stimulation and parameters of secondary esophageal peristalsis in patients with posterior laryngitis (PL). We studied 14 patients (45 +/- 5 years) with PL documented by videolaryngoscopy and 11 healthy controls (46 +/- 6 years). The upper esophageal sphincter (UES) pressure was monitored by a sleeve assembly incorporating an injection port 5 cm distal to the sleeve. The esophageal body and lower esophageal sphincter (LES) pressures were measured by an LES sleeve assembly. Primary esophageal peristalsis was induced by 5-mL water swallows. Secondary esophageal peristalsis was induced by abrupt injection of volumes of air, incrementally increased by 5 mL, into the esophagus. Secondary esophageal peristalsis could not be elicited by injection of any volume (up to 60 mL) in 3 PL patients and 2 controls. These 5 subjects had normal primary peristalsis. The threshold volume of air required to stimulate secondary esophageal peristalsis in PL patients (median, 15 mL) was similar to that of controls (median, 10 mL). The parameters of the secondary esophageal peristaltic pressure wave were similar in both groups, and in both groups, they were similar to those of primary peristalsis. The UES response to the injection of the threshold volume that induced secondary esophageal peristalsis in PL patients was contraction in 58% of the trials, partial relaxation in 3%, and no response in 39%. The findings were similar to those in the controls. The LES response to injection of the threshold volume was complete relaxation in both the PL patients and the controls. We conclude that the integrity of secondary esophageal peristalsis is preserved in PL patients. PMID- 11219524 TI - Thyroarytenoid muscle: functional subunits based on morphology and muscle fiber typing in cats. AB - Using parvalbumin immunohistochemistry to determine the distribution of muscle fiber types in the feline thyroarytenoid muscle (TA), we clearly distinguished the vocalis (with predominance of "slow" type 1 fibers) from the external TA (in which "fast" type 2 fibers predominated, especially in its rostral part). Reconstruction of serial frontal sections of the TA allowed the stereoscopic study of each division. The existence of a rudimentary laryngeal ventricle separating the true and false vocal folds in cats was demonstrated anatomically and histologically, and its relationships to each division of the TA were established. Our results suggest that the vocalis, fitted for enduring activities, is suited for voice control. The fast, rostral part of the external TA seems suited to laryngeal sphincteric demands, while its caudal counterpart may act in both functions. The anatomic individualization of the divisions of the TA may suggest that they play distinct physiological roles and may imply that they should not be considered a single functional unit. PMID- 11219525 TI - Retropharyngeal autologous fat transplantation for congenital short palate: a nasometric assessment of functional results. AB - Seventeen patients (4 to 24 years old; mean, 9.7 years) with mild velopharyngeal insufficiency were treated in our department during the period 1996 to 1999 with augmentation of the posterior pharyngeal wall with autologous fat. The main disorder was a congenital short palate without a cleft, in most cases revealed by adenoidectomy. Four patients had previously undergone pharyngoplasty, and 1 had already been injected in the posterior pharyngeal wall with Teflon paste. All patients had been exhaustively treated with speech therapy, and the result remained unsatisfactory. The functional outcome of the surgical procedure was quantified by acoustic nasometry. The decrease of the nasalance percentage for a standardized spoken passage was significant 1 to 3 months after the fat transplantation, and there was a slight tendency to further reduction of nasality at the late follow-up visit, more than 6 months (average, 9.4 months) after the intervention. The mean value of the nasalance score for the "normal passage" (running speech) then reached the limit of normal values. A long-term follow-up (average, 24.3 months) by telephone questionnaire confirmed the persistence of the beneficial results. Autologous fat seems an excellent alternative for Teflon in this indication. Acoustic nasometry allows a precise quantitative assessment of functional velopharyngeal surgery. PMID- 11219527 TI - Quantitative assessment of the pharyngeal airway by dynamic magnetic resonance imaging in obstructive sleep apnea syndrome. AB - Dynamic changes in the pharyngeal airway of patients with obstructive sleep apnea syndrome (OSAS) were evaluated by quantitating the findings of real-time imaging performed during wakefulness and spontaneous sleep by means of dynamic magnetic resonance imaging (MRI). Six patients with OSAS and 3 non-OSAS subjects, selected prospectively and randomly, underwent polysomnography and dynamic MRI. The cross sectional areas of the soft palate and oropharynx and the anterior-posterior airway dimensions seen during wakefulness and spontaneous sleep were calculated by US National Institutes of Health imaging software. On the basis of a case control study, comparisons were made with age-matched and body mass index-matched obese non-OSAS snorers. Spontaneous sleep caused significant obstruction and narrowing of various sites of the pharyngeal airway in the OSAS patients, but not in the non-OSAS subjects. During wakefulness, the non-OSAS subjects showed no marked narrowing of the pharyngeal airways, whereas a transient but significant narrowing was observed in the OSAS patients. The mean values of both the cross sectional area and the anterior-posterior diameter at the soft palate were significantly reduced by spontaneous sleep in the OSAS patients. Dynamic MRI in awake OSAS patients shows promise as a routine diagnostic tool for localizing the upper airway collapse for appropriate selection of surgical therapy. PMID- 11219528 TI - Effect of cigarette smoking on gastropharyngeal and gastroesophageal reflux. AB - Gastropharyngeal reflux appears to be associated with various otolaryngological complaints. Cigarette smoking is known to affect adversely the defense mechanisms against reflux of acid gastric contents into the esophagus. To study the relationship between gastropharyngeal, as well as gastroesophageal, reflux and cigarette smoking, 15 subjects underwent 24-hour double-probe pH monitoring while smoking their daily amount of cigarettes. The percentage of time the pH was below 4 during the smoking period was significantly higher than the percentage of time the pH was below 4 during the nonsmoking period, proximal, at the level of the upper esophageal sphincter, as well as distal, above the lower esophageal sphincter. These findings demonstrate that smoking increases gastropharyngeal and gastroesophageal reflux. Smokers with complaints and disorders caused by reflux should therefore be advised to stop smoking in order to reduce reflux. PMID- 11219526 TI - Comparison of the microanatomical distributions of macrophages and dendritic cells in normal and diseased tonsils. AB - The palatine tonsils play an important role in immunologic surveillance and resistance to infection in the upper aerodigestive tract. Dendritic cells and macrophages function to capture and process antigen and present it to T lymphocytes, a critical step in the early immune response. Few studies have characterized the distribution and phenotype of those antigen-presenting cells in the normal palatine tonsil, or determined how those parameters change with disease. Immunohistochemical analysis was performed to determine the microanatomical distribution, quantity, morphology, and phenotype of macrophages and dendritic cells in both normal and diseased tonsils. Differences were observed in macrophage and dendritic cell distribution, quantity, and phenotype in the surface and crypt epithelium. The number of macrophages was significantly increased in all compartments in all disease groups (p < .05), although the number of macrophages that expressed phenotypes of maturity and/or activation was not concomitantly increased. In the surface epithelium, Langerhans and interdigitating cells decreased significantly with disease (p < .05). Chronic infection may impose an immunosuppressive effect on responses within tonsil tissue, affecting the immunologic factors responsible for macrophage maturation and activation. PMID- 11219529 TI - Bifid epiglottis associated with Joubert's syndrome. AB - This report presents the case of a 2-year-old boy who had a bifid epiglottis associated with Joubert's syndrome. He had episodic tachypnea and apnea, inspiratory stridor, aspiration, and growth and mental retardation. Direct laryngoscopy demonstrated agenesis of the right half of the epiglottis and hypertrophied mucosa over the arytenoid cartilage. After the hypertrophied mucosa was partially vaporized with a CO2 laser, the inspiratory stridor soon improved and the aspiration was alleviated. Brain magnetic resonance imaging showed cerebellar vermian agenesis and enlargement of the fourth ventricle. PMID- 11219530 TI - Epiglottic tuberculosis: differential diagnosis and treatment. Case report and review of the literature. AB - A case of a 40-year-old man with tuberculous involvement of the epiglottis suffering from unsuspected pulmonary tuberculosis is described. The laryngeal lesions were primarily considered to be highly suspicious for a neoplastic process rather than an infectious one. After diagnosis, the patient was treated according a standard protocol and followed up for a period of 2 years. He is still free of disease. The clinical presentation, diagnosis, pathological findings, and therapy of the condition are described. The differential diagnosis and management of epiglottic tuberculosis are reviewed and discussed. Even though these cases are rare, otorhinolaryngologists should keep in mind the possibility of tuberculosis in the differential diagnosis of laryngeal tumors, as the incidence of tuberculosis in developed countries is steadily increasing. PMID- 11219532 TI - Nuclear energy's debutante. PMID- 11219531 TI - Chondrosarcoma of the nasal septum. PMID- 11219533 TI - The second international in-vivo monitoring intercomparison program for whole body counting facilities by Canadian and United States agencies. AB - The Canadian National Calibration Reference Centre for In-Vivo Monitoring and the United States Department of Energy collaborated to offer a second international in vivo intercomparison program to whole body counting facilities in 1996. This program used a Reference Female phantom shell filled with radioactive tissue substitute polyurethane to simulate a uniform fission-product distribution in soft tissues. The nuclides used were 137Cs and 60Co. The phantom also contained 40K homogeneously distributed in an amount similar to a Reference Female to produce a representative Compton background in the resulting spectra. Participants were asked to identify the nuclides and report activities for all except 40K. They were also asked to measure the precision of counting and supply the MDA for 137Cs and 60Co. The bias results were in the range of -30% to +80% with most facilities falling inside the range of -25% to +50% (Canadian and U.S. acceptable performance criteria). Results indicated that there was no measurable size dependency for this phantom. All reported precisions were less than 5% but NaI detector based systems seemed to have a systematic uncertainty in addition to Poisson variability. Contrarily, this was not found for Ge detector based systems. MDA data was scattered (14-3,500 Bq for 137Cs and 9-460 Bq for 60Co) and only suggested that lengthening the counting time improves MDA. PMID- 11219534 TI - An evaluation of the ethical principles of the ICRP's radiation protection standards for workers. AB - After reviewing international recommendations and national standards for occupational radiation exposures, the article summarizes the major ethical theories so as to analyze which theories various ICRP principles presuppose. It also shows how proponents of each ethical theory would support or criticize various radiation principles and practices. Finally the article discusses four ethical issues crucial to the debate over workplace standards for radiation: (1) how to respond to the uncertainty over effects of low-dose exposures; (2) the conditions under which worker consent legitimates higher exposures; (3) whether there ought to be a double standard for worker, vs. public, exposures; and (4) whether ethics allows money-for-health tradeoffs in radiation protection. The article concludes with several recommendations about how to make occupational exposure to radiation more ethically defensible. PMID- 11219535 TI - In-vivo thyroid 125I monitoring method using imaging plate. AB - A new in vivo thyroid monitoring system was devised with radioluminography using an imaging plate. The counting features of the system were investigated by using a neck-thyroid phantom. A clear thyroid image was obtained at thin prethyroid tissue thicknesses and short distances between IP and neck surface. The characteristic 125I thyroid image made it possible to visually confirm that the thyroid definitely accumulated 125I. The counting efficiency in 100xcps Bq(-1) of the imaging plate system was determined by setting a region of interest on the thyroid image resulting in a maximum efficiency of 0.5%. The higher efficiency was obtained for thinner tissue thickness overlaying the thyroid, smaller thyroids, and shorter distances between the imaging plate and neck surface. The imaging plate thyroid monitoring system was sensitive to thyroid 125I. Its minimum detection limit of 23 Bq for a 10-min measurement was considerably lower than the annual thyroid burden limit of 300 kBq. PMID- 11219536 TI - Age- and sex-specific relative thyroid radiation exposure to 131I in Ukraine after the Chernobyl accident. AB - The age- and sex-dependence of the 131I induced count rates is determined for the measurements performed in Ukraine after the Chernobyl accident on the thyroids of over 60,000 persons. For this, the individual measurements are scaled in such a way that the mean values over age and sex on one side and the mean values over measurement series on the other side are normalized to one. The resulting distribution of all scaled measurements is roughly log-normal. Half of them lie within a factor 1.6 of the median. 131I induced count rates have a minimum at birth year 1986, about half the value of adults. The maximum count rates with about 30% above adults are reached for males around age 16 y. The count rates are up to about 40% (at age 14-17 y) higher for males than for females. The results are within statistical uncertainties independent of the geographical area and the urban or rural nature of the settlements. Starting from the relative count rates, the age- and sex-dependence is calculated for the thyroid activities 1 mo after the accident for the integrated activities and for the doses. The dose of young children is a factor of about 6.5 higher than that of adults. Uncertainties are estimated throughout. PMID- 11219538 TI - Solubility of airborne uranium compounds at the Fernald Environmental Management Project. AB - The in vitro solubility of airborne uranium dusts collected at a former uranium processing facility now undergoing safe shutdown, decontamination, and dismantling was evaluated by immersing air filters from high volume samplers in simulated lung fluid and measuring the 238U in sequential dissolution fractions using specific radiochemical analysis for uranium. X rays and photons from the decay of uranium and thorium remaining on the filter after each dissolution period were also directly measured using a planar germanium detector as a means for rapidly evaluating the solubility of the uranium-bearing dusts. Results of these analyses demonstrate that two distinct types of uranium-bearing dusts were collected on the filters depending upon the location of the air samplers. The first material exhibited a dissolution half-time much less than 1 d and was most likely UO3. The dissolution rate of the second material, which was most likely U3O8, exhibited two components. Approximately one-third of this material dissolved with a half time much less than 1 d. The remaining two-thirds of the material dissolved with half times between 230 +/- 16 d and 1,350 +/- 202 d. The dissolution rates for uranium determined by radiochemical analysis and by gamma spectrometry were similar. However, gamma spectrometry analysis suggested a difference between the half times of 238U and its initial decay product 234Th, which may have important implications for in vivo monitoring of uranium. PMID- 11219537 TI - Calculation of the air concentrations of serially decaying nuclides--a new method applied to radon progeny. AB - A new calculation method is presented for determining the air concentrations of any serially decaying nuclides. This new method is easily incorporated into a Basic or spreadsheet program that is used to record the decay data. Specifically, the measurements were designed to illustrate radon progeny from a filter sample that is gross-alpha counted. The method is based on regressing the decay data, recorded in 1-min intervals, on the time after the end of sampling with an equation that describes the alpha activity as a function of the decay exponentials, e-lambdat. The results from both generated data and experimental filter samples were compared to the results obtained by two other well-known methods. All the methods give comparable estimates for the progeny air concentrations; non-linear regression and weighting by variances produces the smallest error estimates with the method presented here. PMID- 11219539 TI - Deconstructing radiation hormesis. AB - This paper explores some factors that may explain why the possibility of hormesis has not been embraced by the radiation protection community. If shown to be sustainable, hormesis might ameliorate several serious issues plaguing radiation protection including the high economic cost of environmental regulatory compliance and public fear of radiation exposure. Some but not all analyses of data from various sources, including the Japanese survivors of the atomic bombs and residential radon studies, suggest that low levels of ionizing radiation may be beneficial to human health. The evidence, however, has not been viewed as compelling for the following reasons: (1) Data in support of radiation hormesis in human populations is limited and much of it is based on re-evaluation of selected epidemiological data that has been used to test a different hypothesis; (2) Hormetic effects are weak and inconsistent, and are subject to large statistical uncertainties as is the case for carcinogenic effects at small doses; (3) A consensus is lacking on how hormesis should be defined and quantified; and (4) It is unclear how hormesis can be incorporated into the regulatory framework when beneficial health effects exceed the requirement for protection of health. PMID- 11219540 TI - Urinary uranium concentrations in an enlarged Gulf War veteran cohort. AB - Depleted uranium was first used on a large scale as a major component of munitions and armaments employed by the U.S. armed forces during the Gulf War in 1991. In response to concern that exposure to depleted uranium may have been a cause of health problems suffered by returning veterans of that war, an already existing surveillance program following depleted uranium "friendly fire" victims was enlarged to assess the wider veteran community's exposure to depleted uranium. Between August 1998 and December 1999, 169 Gulf War veterans submitted 24-h urine samples for determination of urinary uranium concentration and questionnaires describing their potential exposures to depleted uranium while in the Gulf War theatre. Depleted uranium exposure assessment was determined from 30 separate questionnaire items condensed into 19 distinct exposure scenarios. Results of urine uranium analysis were stratified into high and low uranium groups with 0.05 microg uranium/g creatinine being the cut point and approximate upper limit of the normal population distribution. Twelve individuals (7.1%) exhibited urine uranium values in the high range, while the remaining 157 had urine uranium values in the low range. A repeat test of urine for 6 of these 12 produced uranium results in the low range for 3 of these individuals. Exposure scenarios of the high and low uranium groups were similar with the presence of retained shrapnel being the only scenario predictive of a high urine uranium value. Results emphasize the unlikely occurrence of an elevated urine uranium result and consequently any uranium-related health effects in the absence of retained depleted uranium metal fragments in the veterans. PMID- 11219541 TI - Evaluation of body mass index for a reference Pakistani man and woman. AB - To strengthen the radiation protection infrastructure, a pilot study on physical characteristics for Reference Asian Man was carried out in Pakistan. Physical data on height and weight of Pakistani men and women were collected and compiled for all age groups to establish a Reference Pakistani Man/Woman which contributed toward the Reference Asian Man/Woman. A correlation between Age and Body Mass Index (BMI) of Pakistani MALES (i.e., rm = +0.89) and FEMALES (i.e., rf = +0.71) was observed. Average BMI of Pakistani males and females for the age group of 20 50 y was found to be 21.95 kg m(-2) and 21.20 kg m(-2), respectively. From recent literature and work of others BMI for Reference Asian Male (RAM) and Reference Asian Female (RAF) has been found to be 20.79 kg m(-2) and 20.81 kg m(-2). Results of our study fall within BMI ranges for male/female adults of Asian countries, i.e., 19.14-22.98 kg m(-2) and 19.38-22.71 kg m(-2), respectively. However, no significant sex specific difference has been noted. PMID- 11219543 TI - Comment on "are public dose limits necessary?". PMID- 11219542 TI - Technical procedures for the evaluation of different radiation detection systems at the entrance of a waste incinerator plant. AB - To protect a new waste incinerator plant and the population against the accidental introduction of radioactive material in the furnace, in 1998 the Municipal Service Corporation of the city of Brescia decided to acquire a radiation detection portal system. However, the performance of such instruments is not sufficiently specified in this type of application, so ASM asked the Nuclear Engineering Department of the Polytechnic of Milan to draw up a test protocol and to lead the following experimental campaign. A truck trailer and a source container were prepared ad hoc, and three different systems underwent a sensitivity and a false alarm test. On the basis of the final results, the performance characteristics of various monitoring systems in this particular application were established with the correct degree of accuracy. PMID- 11219545 TI - IAEA D.G. on shutdown on Chernobyl. PMID- 11219544 TI - UNSCEAR 2000 published. United Nations Scientific Committee on the Effects of Atomic Radiation. PMID- 11219546 TI - An overview of fungal infections. AB - The incidence of fungal infections is increasing at an alarming rate, presenting an enormous challenge to healthcare professionals. This increase is directly related to the growing population of immunocompromised individuals, resulting from changes in medical practice such as the use of intensive chemotherapy and immunosuppressive drugs. HIV and other diseases which cause immunosuppression have also contributed to this problem. Superficial and subcutaneous fungal infections affect the skin, keratinous tissues and mucous membranes. Included in this class are some of the most frequently occurring skin diseases, affecting millions of people worldwide. Although rarely life threatening, they can have debilitating effects on a person's quality of life and may in some circumstances spread to other individuals or become invasive. Most superficial and subcutaneous fungal infections are easily diagnosed and readily amenable to treatment. Systemic fungal infections may be caused by either an opportunistic organism that infects an at-risk host, or may be associated with a more invasive organism that is endemic to a specific geographical area. Systemic infections can be life threatening and are associated with high morbidity and mortality. Because diagnosis is difficult and the causative agent is often confirmed only at autopsy, the exact incidence of systemic infections is difficult to determine. The most frequently encountered pathogens are Candida albicans and Aspergillus spp. but other fungi such as non-albicans Candida spp. are increasingly important. PMID- 11219549 TI - Clinical experience with itraconazole in systemic fungal infections. AB - The broad spectrum antifungal itraconazole is an effective and well tolerated agent for the prophylaxis and treatment of systemic fungal infections. The recent development of an itraconazole oral solution and an intravenous itraconazole solution has increased the options for the use of this drug and increased the oral bioavailability in a variety of at-risk patients. Reliable absorption of the itraconazole oral solution has been demonstrated in patients with HIV infection, neutropenic patients with haematological malignancy, bone marrow transplant recipients and neutropenic children. In clinical trials, itraconazole oral solution (5 mg/kg/day) was more effective at preventing systemic fungal infection in patients with haematological malignancy than placebo, fluconazole suspension (100 mg/day) or oral amphotericin-B (2 g/kg/day) and was highly effective at preventing fungal infections in liver transplant recipients. There were no unexpected adverse events with the itraconazole oral solution in any of these trials. In addition, intravenous itraconazole solution is at least as effective as intravenous amphotericin-B in the empirical treatment of neutropenic patients with systemic fungal infections, and drug-related adverse events are more frequent in patients treated with amphotericin-B. A large proportion of patients with confirmed aspergillosis also respond to treatment with intravenous itraconazole followed by oral itraconazole. The new formulations of itraconazole are therefore effective agents for prophylaxis and treatment of most systemic fungal infections in patients with haematological malignancy. PMID- 11219547 TI - Current management of fungal infections. AB - The management of superficial fungal infections differs significantly from the management of systemic fungal infections. Most superficial infections are treated with topical antifungal agents, the choice of agent being determined by the site and extent of the infection and by the causative organism, which is usually readily identifiable. One exception is onychomycosis, which usually requires treatment with systemically available antifungals; the accumulation of terbinafine and itraconazole in keratinous tissues makes them ideal agents for the treatment of onychomycosis. Oral candidiasis in immunocompromised patients also requires systemic treatment; oral fluconazole and itraconazole oral solution are highly effective in this setting. Systemic fungal infections are difficult to diagnose and are usually managed with prophylaxis or empirical therapy. Fluconazole and itraconazole are widely used in chemoprophylaxis because of their favourable oral bioavailability and safety profiles. In empirical therapy, lipid associated formulations of amphotericin-B and intravenous itraconazole are safer than, and at least as effective as, conventional amphotericin-B (the former gold standard). The high acquisition costs of the lipid-associated formulations of amphotericin-B have limited their use. PMID- 11219548 TI - Pharmacology of itraconazole. AB - Itraconazole is a triazole antifungal agent that has a broad spectrum of activity and is well tolerated. Itraconazole is highly efficacious, particularly because its main metabolite, hydroxy-itraconazole, also has considerable antifungal activity. The original capsule formulation of itraconazole may lead to variability in absorption and the plasma concentration. For the treatment of superficial fungal infections, this is not problematical because itraconazole accumulates at the infection site, making consistently high plasma concentrations unnecessary -- a characteristic that has been exploited in the development of a pulse regimen. Because consistent plasma concentrations are critical for the more serious systemic fungal infections, variable absorption of itraconazole from the capsules limits their application. Moreover, underlying disease processes and medical interventions can reduce absorption from the capsules in some patients with systemic fungal infections. To widen the beneficial application of itraconazole to include such patients, an oral solution and an intravenous formulation were developed. These formulations combine lipophilic itraconazole with hydroxypropyl-beta-cyclodextrin, a ring of substituted glucose molecules, which improves the solubility of itraconazole. The enhanced absorption and bioavailability of itraconazole from these new formulations make them ideal for the treatment of systemic fungal infections in a wide range of patient populations. The additional flexibility offered by the different routes of administration also means that itraconazole can be used in patients at high risk, such as children or those requiring intensive care, for whom the capsule formulation may be impractical. PMID- 11219551 TI - Should breech babies be delivered vaginally or by planned cesarean delivery? PMID- 11219552 TI - Are there adverse maternal and neonatal outcomes associated with induction of labor when there is no well-accepted indication? PMID- 11219550 TI - The cost of treating systemic fungal infections. AB - The increasing incidence of systemic fungal infections and rising medical costs have highlighted the need for an economic appraisal of antifungal agents to determine the most cost-effective therapeutic option. Cost savings derived from the prophylactic or empirical use of antifungal agents have been difficult to estimate because of the lack of information on the costs of systemic fungal infections. Fluconazole is effective in prophylaxis and represents a direct cost saving compared with polyenes. However, itraconazole oral solution, an effective and widely used antifungal prophylactic agent, has not been analysed for cost effectiveness. In empirical therapy, the development of new formulations of existing agents has prompted a number of cost comparisons. In particular, the cost of treatment with conventional amphotericin-B has been compared with the costs of the new lipid-associated formulations of amphotericin-B or the new intravenous (IV) formulation of itraconazole. The acquisition costs of lipid associated amphotericin-B and IV itraconazole are higher than the cost of conventional amphotericin-B; however, these costs appear to be offset by reductions with both these agents in the cost for increased length of hospital stay and treating adverse events seen with conventional amphotericin-B. In neutropenic patients and bone marrow transplant recipients, IV itraconazole may be the most cost-effective option for empirical therapy. PMID- 11219553 TI - Is mometasone furoate aqueous nasal spray (MFNS) effective in reducing symptoms in acute recurrent sinusitis? PMID- 11219554 TI - What is the risk of venous thromboembolism (VTE) among women taking third generation oral contraceptives (OCs) in comparison with those taking contraceptives containing levonorgestrel? PMID- 11219555 TI - Clinical inquiries. When should we stop mammography screening for breast cancer in elderly women? PMID- 11219556 TI - Clinical inquiries. Is there any benefit to Papanicolaou (Pap) test screening in women who have had a hysterectomy for benign disease? PMID- 11219557 TI - Care of the secondary patient in family practice. A report from the Ambulatory Sentinel Practice Network. AB - BACKGROUND: Care of a secondary patient (an individual other than the primary patient for an outpatient visit) is common in family practice, but the content of care of this type of patient has not been described. METHODS: In a cross sectional study, 170 volunteer primary care clinicians in 50 practices in the Ambulatory Sentinel Practice Network reported all occurrences of care of a secondary patient during 1 week of practice. These clinicians reported the characteristics of the primary patient and the secondary patient and the content of care provided to the secondary patient. Content of care was placed in 6 categories (advice, providing a prescription, assessment or explanation of symptoms, follow-up of a previous episode of care, making or authorizing a referral, and general discussion of a health condition). RESULTS: Physicians reported providing care to secondary patients during 6% of their office visits. This care involved more than one category of service for the majority of visits involving care of a secondary patient. Advice was provided during more than half the visits. A prescription, assessment or explanation of symptoms, or a general discussion of condition were provided during approximately 30% of the secondary care visits. Secondary care was judged to have substituted for a separate visit 60% of the time, added an average of 5 minutes to the visit, and yielded no reimbursement for 95% of visits. CONCLUSIONS: Care of a secondary patient reflects the provision of potentially intensive and complex services that require additional time and are largely not reimbursed or recognized by current measures of primary care. This provision of secondary care may facilitate access to care and represent an added value provided by family physicians. PMID- 11219558 TI - Routine screening for postpartum depression. AB - BACKGROUND: Postpartum depression (PPD) is a common and often overlooked condition. Validated screening tools for PPD exist but are not commonly used. We present the 1-year outcome of a project to implement universal PPD screening at the 6-week postpartum visit. METHODS: Universal screening with the Edinburgh Postnatal Depression Scale (EPDS) was implemented in all community postnatal care sites. One-year outcome assessments (diagnosis and treatment of PPD) were completed for a sample of the women screened using medical record review of all care they received during the first year postpartum. RESULTS: Sixty-eight (20%) of the 342 women whose medical records were reviewed had been given a documented diagnosis of postpartum depression, resulting in an estimated population rate of 10.7%. Depression was diagnosed in 35% of the women with elevated EPDS scores (> or =10) compared with 5% of the women with low EPDS scores (<10) in the first year postpartum. Treatment was provided for all women diagnosed with depression, including drug therapy for 49% and counseling for 78%. Four women were hospitalized for depression. Some degree of suicidal ideation was noted on the EPDS by 48 women but acknowledged in the chart of only 10 women, including 1 with an immediate hospitalization. The rate of diagnosis of postpartum depression in this community increased from 3.7% before the routine use of EPDS screening to 10.7% following screening. CONCLUSIONS: A high EPDS score was predictive of a diagnosis of postpartum depression, and the implementation of routine EPDS screening at 6 weeks postpartum was associated with an increase in the rate of diagnosed postpartum depression in this community. PMID- 11219559 TI - The quality of physician-patient relationships. Patients' experiences 1996-1999. AB - BACKGROUND: Our objective was to examine how patients of primary care physicians are responding to a changing health care environment. The quality of their relationship with their primary care physicians and their experience with organizational features of care were monitored over a 3-year period. METHODS: This was a longitudinal observational study (1996-1999). Participants completed a self-administered questionnaire at baseline and at follow-up. The questionnaires included measures of primary care quality from the Primary Care Assessment Survey (PCAS). We included insured adults employed by the Commonwealth of Massachusetts who remained with one primary care physician throughout the study period (n=2383). The outcomes were unadjusted mean scale score changes in each of the 8 PCAS over the 3 years and associated standardized difference scores (effect sizes). The 8 PCAS scales measured relationship quality (4 scales: communication, interpersonal treatment, physician's knowledge of the patient, patient trust) and organizational features of care (4 scales: financial access, organizational access, visit-based continuity, integration of care). RESULTS: There were significant declines in 3 of the 4 relationship scales: communication (effect size [ES] = -0.095), interpersonal treatment (ES = -0.115), and trust (ES = 0.046). Improvement was observed in physician's knowledge of the patient (ES = 0.051). There was a significant decline in organizational access (ES = -0.165) and an increase in visit-based continuity (ES = 0.060). There were no significant changes in financial access and integration of care indexes. CONCLUSIONS: The declines in access and 3 of the 4 indexes of physician-patient relationship quality are of concern, especially if they signify a trend. PMID- 11219561 TI - What patients want. PMID- 11219560 TI - Switching doctors: predictors of voluntary disenrollment from a primary physician's practice. AB - BACKGROUND: Our objective was to evaluate 8 interpersonal and structural features of care as predictors of patients' voluntary disenrollment from their primary care physician's practice. METHODS: We performed a longitudinal observational study in which participants completed a validated questionnaire at baseline (1996) and follow-up (1999). The questionnaire measured 4 elements of the quality of physician-patient relations (communication, interpersonal treatment, physician's knowledge of the patient, and patient trust) and 4 structural features of care (access, visit-based continuity, relationship duration, and integration of care). Study participants were insured adults who reported having a regular personal physician at baseline and who completed both baseline and follow-up questionnaires (n=4108). The outcome measured was voluntary disenrollment from the primary physician's practice between baseline and follow up. RESULTS: One fifth of the patients voluntarily left their primary physician's practice during the study period. When tested independently, all 8 scales significantly predicted voluntary disenrollment (P <.001), with somewhat larger effects associated with the 4 relationship quality measures. In multivariable models, a composite relationship quality factor most strongly predicted voluntary disenrollment (odds ratio [OR]=1.6; P<.001), and the 2 continuity scales also significantly predicted disenrollment (OR=1.1; P<.05). Access and integration did not significantly predict disenrollment in the presence of these variables. CONCLUSIONS: These findings highlight the importance of relationship quality in determining patients' loyalty to a physician's practice. They suggest that in the race to the bottom line medical practices and health plans cannot afford to ignore that the essence of medical care involves the interaction of one human being with another. PMID- 11219562 TI - Enhancing smoking cessation of low-income smokers in managed care. AB - BACKGROUND: Although office-based and telephone support services enhance the rate of smoking cessation in managed care systems, it is not clear whether such services are effective for very low-income smokers. We evaluated the comparative effectiveness of usual care (physician-delivered advice and follow-up) and usual care enhanced by 6 computer-assisted telephonic-counseling sessions by office nurses and telephone counselors for smoking cessation in very low-income smokers in Medicaid managed care. METHODS: A randomized clinical trial comparing the 2 approaches was conducted in 3 Michigan community health centers. All clinicians and center staff received standard training in usual care. Selected nurses and telephone counselors received special training in a computer-assisted counseling program focusing on relapse prevention. RESULTS: The majority of the study population (233 adult smokers with telephones) were white (64%) women (70%) with annual incomes of less than $10,000 (79%) and with prescriptions of nicotine replacement therapy (>90%). At 3 months, quit rates (smoke-free status verified by carbon monoxide monitors) were 8.1% in the usual-care group and 21% in the telephonic-counseling group (P=.009) by intention-to-treat analysis. Special tracking methods were successful in maintaining participants in treatment. CONCLUSIONS: Smoking cessation rates are enhanced in a population of very low income smokers if individualized telephonic-counseling is provided. State and Medicaid managed care plans should consider investing in both office-based nurse and centralized telephonic-counseling services for low-income smokers. PMID- 11219563 TI - Opioids for chronic nonmalignant pain. Attitudes and practices of primary care physicians in the UCSF/Stanford Collaborative Research Network. University of California, San Francisco. AB - BACKGROUND: We hoped to determine the attitudes and practices of primary care physicians regarding the use of opioids to treat chronic nonmalignant pain (CNMP). We also examined the factors associated with the willingness to prescribe opioids for CNMP. METHODS: A survey was mailed to primary care physicians in the University of California, San Francisco/Stanford Collaborative Research Network. This survey contained questions regarding treatment in response to 3 case vignettes, the use of opioids for CNMP in general, and the demographic characteristics of the physicians. RESULTS: Among 230 physicians surveyed, 161 (70%) responded. Two percent of the respondents were never willing to prescribe schedule III opioids (eg, acetaminophen with codeine) as needed for patients with CNMP that persisted unchanged after exhaustive evaluation and attempts at treatment. Thirty-five percent were never willing to prescribe schedule II opioids (eg, sustained-release morphine) on an around-the-clock schedule for these patients. The most significant predictor of willingness to prescribe opioids for patients with CNMP was a lower level of concern about physical dependence, tolerance, and addiction. CONCLUSIONS: Primary care physicians are willing to prescribe schedule III opioids as needed, but many are unwilling to use schedule II opioids around the clock for CNMP. Individual prescribing practices vary widely among primary care physicians. Concerns about physical dependence, tolerance, and addiction are barriers to the prescription of opioids by primary care physicians for patients with CNMP. PMID- 11219564 TI - Meeting the challenge of chronic pain. PMID- 11219565 TI - The role of gynecologists in providing primary care to elderly women. AB - BACKGROUND: Federal legislation has recently been proposed to designate obstetrician-gynecologists (OBGs) as primary care physicians. The Institute of Medicine identifies care unrestricted by problem or organ system as an essential characteristic of primary care. We examined the degree to which OBGs in the state of Washington offer this aspect of primary care to their elderly patients by investigating the type and amount of nongynecologic care they provide. METHODS: Using 1994 Part B Medicare claims data for Washington residents, we identified visits made by women aged 65 years and older to OBGs (N=10,522) and 9 other types of specialists. Diagnoses were classified as in or out of the domain of care traditionally provided by each specialty. Visit volumes, proportion of out of domain visits, and the frequency of diagnoses were reported. RESULTS: Of the patient visits to obstetrician-gynecologists, 12.2% had nongynecologic diagnoses. The median percentage of nongynecologic visits for individual OBGs was 6.7%. Patients who saw OBGs received 15.4% of their overall health care from an OBG; patients who saw family physicians received 42.9% of their total health care from a family physician. CONCLUSIONS: In 1994, a small amount of the care that Washington OBGs provided to their elderly patients was for nongynecologic conditions. Studies are needed to evaluate how the practices of OBGs have changed since the 1996 implementation of a primary care requirement in obstetrics gynecology residencies, and if adopted, how legislation designating OBGs as primary care physicians affects the health care received by elderly women. PMID- 11219566 TI - Evaluation of the patient with suspected deep vein thrombosis. PMID- 11219567 TI - Does the increased sensitivity of the new Papanicolaou (Pap) tests improve the cost-effectiveness of screening for cervical cancer? PMID- 11219568 TI - What is the optimal strategy for managing acute migraine headaches? PMID- 11219569 TI - Do back-up antibiotic prescriptions for the treatment of common respiratory symptoms alter fill rates and patient satisfaction? PMID- 11219570 TI - Is cilostazol more effective than pentoxifylline in the treatment of symptoms of intermittent claudication? PMID- 11219571 TI - Ultrasound-assisted physical examination. PMID- 11219572 TI - Childhood vaccinations. PMID- 11219573 TI - Chlorophyll is not the primary photoreceptor for the stimulation of P-type H+ pump and growth in variegated leaves of Coleus x hybridus. AB - There has been persisting controversy over the role of photosynthesis in the stimulation of the plasma membrane H+-ATPase and growth of dicotyledonous leaves by light. To investigate this, we compared the effects of light on growth, H+ net efflux and membrane potential (Vm) of strips which contained either only chlorophyll-free (white) mesophyll cells or chlorophyll-containing (green) cells cut from variegated Coleus leaves. White mesophyll cells responded to white, blue and red light with a hyperpolarization of Vm, an acidification of the apoplast and a promotion of growth, all of which began after a lag of 2-7 min. In contrast, green mesophyll cells showed a biphasic light response in which the hyperpolarization and the acidification were preceded by a rapid depolarization of Vm and an alkalinization of the apoplast. Nevertheless, green and white tissues showed comparable growth promotions in response to light. The light response of the leaf mesophyll is a composite of two separate photosystems. The initial depolarization and alkalinization are mediated by photosynthesis and blocked by 3-(3,4-dichlorophenyl)-1,1-dimethylurea. The slower hyperpolarization, acidification and growth response, on the other hand, are clearly in response to light absorption by pigments other than chlorophyll. PMID- 11219574 TI - Thermodynamic analysis of diffusion of non-electrolytes across plant cuticles in the presence and absence of the plasticiser tributyl phosphate. AB - Solute mobility in cuticular membranes (CMs) of 14 plant species (Citrus aurantiumn L., Citrus grandis L., Hedera helix L., Ilex aquifolium L., Ilex paraguariensis St.-Hil., Malus domestica Borkh. cv. Golden Delicious, Populus alba L., Prunus laurocerasus L., Pyrus communis L. cv. Bartlett, Conference and Gellerts Butterbirne, Pyrus pyrifolia (Burm. f.) Nakai, Schefflera actinophylla (Endl.) Harms and Strophanthus gratus Baill.) was measured over the temperature range 25-55 degrees C. The five organic model compounds differed in size (130-349 cm3 mol(-1)) and cuticle/water partition coefficient (18-10(8)). For all individual CMs (n = 297), the data were plotted according to the thermodynamic relationship between the preexponential factor (which is proportional to entropy) of the Arrhenius equation and the activation energy (enthalpy) of diffusion (ED). A strict linear correlation was obtained, providing evidence that the five compounds diffused along the same lipophilic diffusion path in all plant species tested. Extracting cuticular waxes from CMs of four plant species (Hedera, Pyrus, Schefflera and Strophanthus) had no effect on the slope of the plot but a parallel displacement towards higher entropy was observed with these polymer matrix (MX) membranes. This displacement is interpreted as a temperature independent tortuosity factor directly related to entropy. The influence of the plasticiser tributyl phosphate on solute mobility at various temperatures was measured for CM and MX membranes. The plasticiser increased solute mobility and ED was reduced drastically for both membrane types. This plasticiser effect was almost completely reversible, when tributyl phosphate was desorbed from the membranes. For both, plasticised CM and MX, the thermodynamic correlation exists whereby all data points lie on the same line. The data are used to characterise the lipophilic pathway across plant cuticles in terms of the free-volume theory. PMID- 11219575 TI - Calcium chloride penetrates plant cuticles via aqueous pores. AB - Penetration of calcium chloride across astomatous cuticular membranes (CMs) isolated from leaves of Pyrus communis L. has been studied. Penetration was a first-order process when calcium chloride concentrations ranged from 2 gl(-1) to 10 gl(-1). Rate constants were increased 10-fold by adding wetting agents but they did not depend on temperature. The accelerators tributyl phosphate and diethyl sebacate had no effect on rates of penetration. Increasing humidity over the salt residue on the CMs from 50 to 90% increased rate constants by about 2 fold. Extracting cuticular waxes from pear leaf CMs increased rate constants by factors of 2 to 3, depending on humidity. Leaf CMs from Malus domestica Borkh., Populus aelha L., Stephanotis floribunda Brongn. and Schefflera actinophylla (Endl.) Harms were also permeable to CaCl2. Highest rate constants were observed with poplar CMs while Schefflera CMs exhibited the lowest permeability. By comparing these results with the well established transport properties of the lipophilic pathway it is concluded that calcium chloride hexahydrate penetrated cuticular membranes via aqueous pores. PMID- 11219576 TI - 3-hydroxy-3-phenylpropanoic acid is an intermediate in the biosynthesis of benzoic acid and salicylic acid but benzaldehyde is not. AB - Stable-isotope-labelled (2H6, 18O) 3-hydroxy-3-phenylpropanoic acid, a putative intermediate in the biosynthesis of benzoic acid (BA) and salicylic acid (SA) from cinnamic acid, has been synthesized and administered to cucumber (Cucumis sativus L.) and Nicotiana attenuata (Torrey). Analysis of the products by gas chromatography-mass spectrometry revealed incorporation of labelling into BA and SA, but not into benzaldehyde. In a separate experiment, 3-hydroxy-3 phenylpropanoic acid was found to be a metabolite of phenylalanine, itself the primary metabolic precursor of BA and SA. These data suggest that cinnamic acid chain shortening is probably achieved by beta-oxidation, and that the proposed "non-oxidative" pathway of side-chain degradation does not function in the biosynthesis of BA and SA, in cucumber and N. attenuata. PMID- 11219577 TI - Studies on water transport through the sweet cherry fruit surface: characterizing conductance of the cuticular membrane using pericarp segments. AB - Water conductance of the cuticular membrane (CM) of mature sweet cherry fruit (Prunus avium L. cv. Sam) was investigated by monitoring water loss from segments of the outer pericarp excised from the cheek of the fruit. Segments consisted of epidermis, hypodermis and several cell layers of the mesocarp. Segments were mounted in stainless-steel diffusion cells with the mesocarp surface in contact with water, while the outer cuticular surface was exposed to dry silica (22 +/- 1 degrees C). Conductance was calculated by dividing the amount of water transpired per unit area and time by the difference in water vapour concentration across the segment. Conductance values had a log normal distribution with a median of 1.15 x 10(-4) m s(-1) (n=357). Transpiration increased linearly with time. Conductance remained constant and was not affected by metabolic inhibitors (1 mM NaN3 or 0.1 mM carbonylcyanide m-chlorophenylhydrazone) or thickness of segments (range 0.8 2.8 mm). Storing fruit (up to 42 d, 1 degrees C) used as a source of segments had no consistent effect on conductance. Conductance of the CM increased from cheek (1.16 +/- 0.10 x 10(-4) m s(-1)) to ventral suture (1.32 +/- 0.07 x 10(-4) m s( 1)) and to stylar end (2.53 +/- 0.17 x 10(-4) m s(-1)). There was a positive relationship (r2=0.066**; n=108) between conductance and stomatal density. From this relationship the cuticular conductance of a hypothetical astomatous CM was estimated to be 0.97 +/- 0.09 x 10(-4) m s(-1). Removal of epicuticular wax by stripping with cellulose acetate or extracting epicuticular plus cuticular wax by dipping in CHCl3/methanol increased conductance 3.6- and 48.6-fold, respectively. Water fluxes increased with increasing temperature (range 10-39 degrees C) and energies of activation, calculated for the temperature range from 10 to 30 degrees C, were 64.8 +/- 5.8 and 22.2 +/- 5.0 kJ mol(-1) for flux and vapour concentration-based conductance, respectively. PMID- 11219578 TI - A cDNA encoding 3-deoxy-D-manno-oct-2-ulosonate-8-phosphate synthase of Pisum sativum L. (pea) functionally complements a kdsA mutant of the Gram-negative bacterium Salmonella enterica. AB - Recombinant plasmids encoding 3-deoxy-D-manno-oct-2-ulosonate-8-phosphate (Kdo-8 P) synthase (KdsA; EC 4.1.2.16) were identified from a cDNA library of Pisum sativum L. (pea) by complementing a temperature-sensitive kdsA(ts) mutant of the Gram-negative bacterium Salmonella enterica. Sequence analysis of several inserts revealed a central open reading frame encoding a protein of 290 amino acids with a high degree of amino acid sequence similarity to bacterial KdsA. The cDNA was confirmed by amplifying a 1,812-bp DNA fragment from the chromosome of pea that encoded four exons around the 5'-end of kdsA. The recombinant enzyme was subcloned, overexpressed and characterized to synthesize Kdo-8-P from D-arabinose 5-phosphate and phosphoenolpyruvate. The pH optimum was 6.1 and the activity of the enzyme was neither stimulated by the addition of divalent cations nor inhibited by EDTA. The cDNA of kdsA could not complement Escherichia coli K-12 strain AB3257, which is defective in all three isoenzymes (AroFGH) of 3-deoxy-D arabino-hept-2-ulosonate-7-phosphate (Dha-7-P) synthase (EC 4.1.2.15), and neither D-erythrose-4-phosphate nor D-ribose-5-phosphate could substitute for D arabinose-5-phosphate in vitro. Thus, plant cells possess a specific enzyme for the biosynthesis of Kdo-8-P with remarkable structural and functional similarities to bacterial KdsA proteins. PMID- 11219579 TI - Barley Mla and Rar mutants compromised in the hypersensitive cell death response against Blumeria graminis f.sp. hordei are modified in their ability to accumulate reactive oxygen intermediates at sites of fungal invasion. AB - The pathogenesis-related accumulation of superoxide radical anions (O2*-) and hydrogen peroxide (H2O2) was comparatively analyzed in a barley line (Hordeum vulgare L. cv Sultan-5) carrying the powdery mildew (Blumeria graminis f.sp. hordei, Speer, Bgh) resistance gene Mla12, and in susceptible mutants defective in Mla12 or in genes "required for Mla12-specified disease resistance" (Rar1 and Rar2). In-situ localization of reactive oxygen intermediates was performed both by microscopic detection of azide-insensitive nitroblue tetrazolium (NBT) reduction or diaminobenzidine (DAB) polymerization, and by an NBT-DAB double staining procedure. The Mla12-mediated hypersensitive cell death occurred either in attacked epidermal cells or adjacent mesophyll cells of wild-type plants. Whole-cell H2O2 accumulation was detected in dying cells, while O2*- emerged in adjacent cells. Importantly, all susceptible mutants lacked these reactions. An oxalate oxidase, which is known to generate H2O2 and has been implicated in barley resistance against the powdery mildew fungus, was not differentially expressed between the wild type and all mutants. The results demonstrate that the Rar1 and Rar2 gene products, which are control elements of R-gene-mediated programmed cell death, also control accumulation of reactive oxygen intermediates but not the pathogenesis-related expression of oxalate oxidase. PMID- 11219580 TI - Celery (Apium graveolens L.) parenchyma cell walls examined by atomic force microscopy: effect of dehydration on cellulose microfibrils. AB - Atomic force microscopy (AFM) was used to image celery (Apium graveolens L.) parenchyma cell walls in situ. Cellulose microfibrils could clearly be distinguished in topographic images of the cell wall. The microfibrils of the hydrated walls appeared smaller, more uniformly distributed, and less enmeshed than those of dried peels. In material that was kept hydrated at all times and imaged under water, the microfibril diameter was mainly in the range 6-25 nm. The cellulose microfibril diameters were highly dependent on the water content of the specimen. As the water content was decreased, by mixing ethanol with the bathing solution, the microfibril diameters increased. Upon complete dehydration of the specimen we observed a significant increase in microfibril diameter. The procedure used to dehydrate the parenchyma cells also influenced the size of cellulose microfibrils with freeze-dried material having larger diameters than air-dried material. PMID- 11219581 TI - The distribution of caprylate, caprate and laurate in lipids from developing and mature seeds of transgenic Brassica napus L. AB - The composition and positional distribution of lipids in developing and mature transgenic Brassica napus seeds accumulating up to 7 mol% of caprylate (8:0), 29 mol% caprate (10:0) or 63 mol% of laurate (12:0) were examined. The accumulation of 8:0 and 10:0 resulted from over-expression of the medium-chain-specific thioesterase (Ch FatB2) alone or together with the respective chain-length specific condensing enzyme (Ch KASIV). Seeds containing high levels of 12:0 were obtained from plants expressing bay thioesterase (BTE) alone or crossed with a line over-expressing the coconut lysophosphatidic acid acyltransferase (LPAAT), an enzyme responsible for the increase in acylation of 12:0 at the sn-2 position. In all instances, 10:0 and 12:0 fatty acids were present in substantial amounts in phosphatidylcholine during seed development with a drastic decrease of 80-90% in mature seeds. At all stages of seed development however, 8:0 was barely detectable in this membrane lipid. Altogether, these results indicate that these transgenic seeds exclude and/or remove the medium-chain fatty acids from their membrane and that this mechanism(s) is more effective with the shorter-chain fatty acids. Furthermore, seeds of 8:0- and 10:0-producing lines had only negligible levels of these fatty acids present in the sn-2 position of the triacylglycerols. In contrast, all 12:0-producing seeds had a substantial amount of this fatty acid in the sn-2 position of the triacylglycerols, suggesting that the endogenous LPAAT is able to acylate 12:0 if no other acyl-CoA species are available. PMID- 11219582 TI - Characterization and expression of the Douglas-fir luminal binding protein (PmBiP). AB - The endoplasmic reticulum (ER) molecular chaperone, BiP, plays a role in the cotranslational translocation and subsequent folding and assembly of newly synthesized proteins targeted to the ER and secretory pathway. The sequence encoding a Douglas-fir (Pseudotsuga menziesii [Mirb] Franco) BiP homologue (PmBiP) was identified by differential screening of a seedling cDNA library. Southern blotting indicated that PmBiP is most likely present as a single copy. The deduced amino acid sequence of PmBiP contains an HEEL tetrapeptide sequence which functions to retain PmBiP in the ER and is different from HDEL commonly found in angiosperm plant BiPs. Amino acid sequence alignment and phylogenetic analysis show that PmBiP is highly similar to other plant BiPs yet forms a distinct phylogenetic subgroup which is separate from the angiosperm BiPs. Northern and western blotting revealed that PmBiP is subject to developmental regulation during seed development, germination, and early seedling growth and is seasonally regulated in needles of young seedlings. PMID- 11219583 TI - Regulation of protoporphyrin IX biosynthesis by intraplastidic compartmentalization and adenosine triphosphate. AB - Subplastidic preparations from cotyledons of cucumber (Cucumis sativus L.) were tested for their ability to synthesize protoporphyrin IX from the substrate 5 aminolevulinic acid. Envelope or thylakoid membranes failed to synthesize protoporphyrin IX from the substrate 5-aminolevulinic acid. Stromal preparations synthesized a very low amount of protoporphyrin IX. In a reconstitution experiment using stroma + envelope membranes, protoporphyrin IX synthesis from 5 aminolevulinic acid was enhanced by 660% over that of stroma alone. However, when thylakoids were added to the stroma + envelope mixture, protoporphyrin IX synthesis from 5-aminolevulinic acid was completely inhibited. In the reconstituted stroma + envelope membrane mixture, the reducing agent dithiothreitol enhanced the protoporphyrin IX-synthesizing ability and completely abolished the inhibition of protoporphyrin IX synthesis by thylakoids. This suggested that the oxidizing agents usually associated with the thylakoid membranes inhibited protoporphyrin IX biosynthesis and the inhibition was alleviated by the reducing power of dithiothreitol. This study exposes the weakness of in vitro reconstitution experiments in mimicking the in vivo conditions. Addition of ATP stimulated protoporphyrin IX synthesis by 50% in the supernatant fraction of chloroplast lysate. This ATP-induced stimulation of protoporphyrin IX synthesis was due to the enhancement of the activities of uroporphyrinogen decarboxylase and protoporphyrinogen oxidase, involved in tetrapyrrole biosynthesis. The ATP-induced stimulation of porphyrinogen oxidase activity was an energy-dependent reaction. PMID- 11219585 TI - Effect of heat stress on the inhibition and recovery of the ribulose-1,5 bisphosphate carboxylase/oxygenase activation state. AB - Experiments were conducted to determine the relative contributions of ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco; EC 4.1.1.39) activation state vis-a-vis Rubisco activase and metabolite levels to the inhibition of cotton (Gossypium hirsutum L.) photosynthesis by heat stress. Exposure of leaf tissue in the light to temperatures of 40 or 45 degrees C decreased the activation state of Rubisco to levels that were 65 or 10%, respectively, of the 28 degrees C control. Ribulose-1,5-bisphosphate (RuBP) levels increased in heat-stressed leaves, whereas the 3-phosphoglyceric acid pool was depleted. Heat stress did not affect Rubisco per se, as full activity could be restored by incubation with CO2 and Mg2+. Inhibition and recovery of Rubisco activation state and carbon dioxide exchange rate (CER) were closely related under moderate heat stress (up to 42.5 degrees C). Moderate heat stress had negligible effect on Fv/Fm, the maximal quantum yield of photosystem II. In contrast, severe heat stress (45 degrees C) caused significant and irreversible damage to Rubisco activation, CER, and Fv/Fm. The rate of Rubisco activation after alleviating moderate heat stress was comparable to that of controls, indicating rapid reversibility of the process. However, moderate heat stress decreased both the rate and final extent of CER activation during dark-to-light transition. Treatment of cotton leaves with methyl viologen or an oxygen-enriched atmosphere reduced the effect of heat stress on Rubisco inactivation. Both treatments also reduced tissue RuBP levels, indicating that the amount of RuBP present during heat stress may influence the degree of Rubisco inactivation. Under both photorespiratory and non photorespiratory conditions, the inhibition of the CER during heat stress could be completely reversed by increasing the internal partial pressure of CO2 (Ci). However, the inhibition of the CER by nigericin, a K+ ionophore, was not reversible when the Ci was increased at ambient or high temperature. Our results indicate that inhibition of photosynthesis by moderate heat stress is not caused by inhibition of the capacity for RuBP regeneration. We conclude that heat stress inhibits Rubisco activation via a rapid and direct effect on Rubisco activase, possibly by perturbing Rubisco activase subunit interactions with each other or with Rubisco. PMID- 11219584 TI - Molecular cloning and characterization of a tomato cDNA encoding a systemically wound-inducible bZIP DNA-binding protein. AB - Localized wounding of one leaf in intact tomato (Lycopersicon esculentum Mill.) plants triggers rapid systemic transcriptional responses that might be involved in defense. To better understand the mechanism(s) of intercellular signal transmission in wounded tomatoes, and to identify the array of genes systemically up-regulated by wounding, a subtractive cDNA library for wounded tomato leaves was constructed. A novel cDNA clone (designated LebZIP1) encoding a DNA-binding protein was isolated and identified. This clone appears to be encoded by a single gene, and belongs to the family of basic leucine zipper domain (bZIP) transcription factors shown to be up-regulated by cold and dark treatments. Analysis of the mRNA levels suggests that the transcript for LebZIP1 is both organ-specific and up-regulated by wounding. In wounded wild-type tomatoes, the LebZIP1 mRNA levels in distant tissue were maximally up-regulated within only 5 min following localized wounding. Exogenous abscisic acid (ABA) prevented the rapid wound-induced increase in LebZIP1 mRNA levels, while the basal levels of LebZIP1 transcripts were higher in the ABA mutants notabilis (not), sitiens (sit), and flacca (flc), and wound-induced increases were greater in the ABA deficient mutants. Together, these results suggest that ABA acts to curtail the wound-induced synthesis of LebZIP1 mRNA. PMID- 11219587 TI - Alpha-expansins in the semiaquatic ferns Marsilea quadrifolia and Regnellidium diphyllum: evolutionary aspects and physiological role in rachis elongation. AB - To investigate the evolutionary history of expansins and their role in cell elongation in early land plants, we isolated two alpha-expansin genes, Mq-EXP1 and Rd-EXP1, respectively, from the semiaquatic ferns Marsilea quacdrifolia L. and Regnellidium diphyllum Lindm. The deduced amino acid sequences of the fern expansins exhibit a high degree of identity to those of seed plants, showing that expansin genes were conserved during the evolution of vascular plants. Gel-blot analysis of M. quadrifolia and R. diphyllum genomic DNA indicated that, in both ferns, alpha-expansins are encoded by multigene families. Expression of alpha expansin genes probed with Mq-EXP1 was confined to the elongating region of the Marsilea rachis. Cell-wall proteins of M. quadrifolia induced in-vitro extension of acidified cucumber cell walls. In R. diphyllum, expression of Rd-EXP1 increased when elongation of the rachis was enhanced by submergence or ethylene. These results indicate that alpha-expansins act as wall-loosening proteins in ferns, as has been proposed for angiosperms. In addition, Rd-EXP1 may play a role in mediating elongation of the rachis in submerged plants. PMID- 11219586 TI - Cellular compartmentation of cadmium and zinc in relation to other elements in the hyperaccumulator Arabidopsis halleri. AB - The cellular compartmentation of elements was analysed in the Zn hyperaccumulator Arabidopsis halleri (L.) O'Kane & Al-Shehbaz (=Cardaminopsis halleri) using energy-dispersive X-ray microanalysis of frozen-hydrated tissues. Quantitative data were obtained using oxygen as an internal standard in the analyses of vacuoles, whereas a peak/background ratio method was used for quantification of elements in pollen and dehydrated trichomes. Arabidopsis halleri was found to hyperaccumulate not only Zn but also Cd in the shoot biomass. While large concentrations of Zn and Cd were found in the leaves and roots, flowers contained very little. In roots grown hydroponically, Zn and Cd accumulated in the cell wall of the rhizodermis (root epidermis), mainly due to precipitation of Zn/Cd phosphates. In leaves, the trichomes had by far the largest concentrations of Zn and Cd. Inside the trichomes there was a striking sub-cellular compartmentation, with almost all the Zn and Cd being accumulated in a narrow ring in the trichome base. This distribution pattern was very different from that for Ca and P. The epidermal cells other than trichomes were very small and contained lower concentrations of Zn and Cd than mesophyll cells. In particular, the concentrations of Cd and Zn in the mesophyll cells increased markedly in response to increasing Zn and Cd concentrations in the nutrient solution. This indicates that the mesophyll cells in the leaves of A. halleri are the major storage site for Zn and Cd, and play an important role in their hyperaccumulation. PMID- 11219588 TI - Light-induced pH and K+ changes in the apoplast of intact leaves. AB - The K +-sensitive fluorescent dye benzofuran isophthalate (PBFI) and the pH sensitive fluorescein isothiocyanate dextran (FITC-Dextran) were used to investigate the influence of light/dark transitions on apoplastic pH and K+ concentration in intact leaves of Vicia faba L. with fluorescence ratio imaging microscopy. Illumination by red light led to an acidification in the leaf apoplast due to light-induced H+ extrusion. Similar apoplastic pH responses were found on adaxial and abaxial sides of leaves after light/dark transition. Stomatal opening resulted only in a slight pH decrease (0.2 units) in the leaf apoplast. Gradients of apoplastic pH exist in the leaf apoplast, being about 0.5 1.0 units lower in the center of the xylem veins as compared with surrounding cells. The apoplastic K+ concentration in intact leaves declined during the light period. A steeper light-induced decrease in apoplastic K+, possibly caused by higher apoplastic K+, was found on the abaxial side of leaves concentration. Simultaneous measurements of apoplastic pH and K+ demonstrated that a light induced decline in apoplastic K- concentration indicative of net K+ uptake into leaf cells occurs independent of apoplastic pH changes. It is suggested that the driving force that is generated by H+ extrusion into the leaf apoplast due to H+ ATPase activity is sufficient for passive K+ influx into the leaf cells. PMID- 11219589 TI - The role of growth rate, redox-state of the plastoquinone pool and the trans thylakoid deltapH in photoacclimation of Chlorella vulgaris to growth irradiance and temperature. AB - The long-term photoacclimation of Chlorella vulgaris Beijer (UTEX 265) to growth irradiance and growth temperature under ambient CO2 conditions was examined. While cultures grew at a faster rate at 27 than at 5 degrees C, growth rates appeared to be independent of irradiance. Decreases in light-harvesting polypeptide accumulation, increases in xanthophyll pool size and changes in the epoxidation state of the xanthophyll cycle pigments were correlated linearly with increases in the relative reduction state of QA, the primary quinone receptor of photosystem II, when estimated as 1-qP under steady-state growth conditions. However, we show that there is also a specific temperature-dependent component, in addition to the redox-state of the QA, involved in regulating the content and composition of light-harvesting complex II of C. vulgaris. In contrast, modulation of the epoxidation state of the xanthophyll pool in response to increased 1-qP in cells grown at 5 degrees C was indistinguishable from that of cells grown at 27 degrees C, indicating that light and temperature interact in a similar way to regulate xanthophyll cycle activity in C. vulgaris. Because C. vulgaris exhibited a low-light phenotype in the presence of 3-(3,4 dichlorophenyl)-1,1-dimethylurea (DCMU), but a high-light phenotype upon addition of 2,5-dibromo-6-isopropyl-3-methyl-1,4-benzoquinone, we conclude that the plastoquinone pool acts as a sensor regulating the accumulation of light harvesting polypeptides in C. vulgaris. However, concomitant measurements of non photochemical fluorescence quenching (qN) and the epoxidation state of the xanthophyll pool appear to indicate that, in addition to the redox-state of the plastoquinone pool, the trans-thylakoid deltapH may also contribute to sensing changes in irradiance and temperature that would lead to over-excitation of the photosynthetic apparatus. We suggest that sink capacity as reflected in photosynthate utilization and cell growth ultimately regulate photoacclimation in C. vulgaris. PMID- 11219590 TI - Early pregnancy failure--current management concepts. AB - Approximately one in four women will experience a miscarriage during her lifetime. For more than 50 years, the standard management of early pregnancy failure has been a dilatation and curettage (D & C). Typically, the procedure is performed in an operating room, which significantly increases cost. There is little objective information in the modem literature to prove that a D & C for all patients will lower morbidity or improve emotional well being. Treatment options include expectant management, D & C in an outpatient setting, and medical management with misoprostol (not approved by the U.S. Food and Drug Administration for treatment of early pregnancy failure). The medical literature supports that expectant management may result in more complications, including the need for "emergent" curettage, if clinicians do not understand the true normal course of expectant management. In general, women prefer some form of active management. Dilatation and curettage can be performed safely in the office or other outpatient setting using manual vacuum aspiration. Vaginal misoprostol will cause expulsion in 80% to 90% of women up to 13 weeks' uterine size or gestation, including patients who have a gestational sac present. However, these data come from only three trials involving a total of 42 subjects treated with vaginal misoprostol, and another study of 42 women who received vaginal misoprostol for "missed abortion" before a scheduled D & C. There is a significant lack of information from large-scale studies about when treatment is necessary and the relative efficacy, rates of side effects, and acceptability of these various treatment options for early pregnancy failure. PMID- 11219591 TI - Anesthesia and analgesia for newborn circumcision. AB - Newborn circumcision is likely the most common elective surgical procedure performed in children, yet a sizable portion of these procedures is performed without anesthesia or analgesia. This review discusses methods and techniques of analgesia and anesthesia for newborn circumcision. Behavioral, pharmacological, and regional block techniques are described. Ideally, the use of a combination of local anesthesia and behavioral techniques are most beneficial to newborns that undergo this painful procedure. PMID- 11219592 TI - A guest editorial: a pragmatic approach to gestational diabetes. PMID- 11219593 TI - Laparoscopic presacral neurectomy: a review. AB - Dysmenorrhea can be a severe and debilitating symptom in many women. Although most women may find adequate relief of symptoms from pharmacological approaches, there remain a few with resistant pain. Presacral neurectomy, although technically challenging, may be offered after other approaches are unsuccessful. The operation is now performed increasingly by the laparoscopic approach, which has revived this operation in some centers. The anatomy, technique, and indications as well as a review of the literature supporting this operation are reviewed. The potential complications of this operation are discussed also. PMID- 11219594 TI - Non-invasive assessment of graft patency using transcutaneous Doppler echocardiography for the validation of functional improvement after PTCA of the LAD via internal thoracic artery graft. AB - Percutaneous transluminal coronary angioplasty (PTCA) of a native coronary artery via internal thoracic artery (ITA) graft after bypass surgery is a relatively rare procedure. Our current study evaluates the flow velocity patterns of the graft before and after PTCA. After intervention the mean diastolic flow velocity increased under rest and stress conditions. In addition, the graft patency was proved not before control angiography after 6 months. It could be verified that the measurement of flow velocity patterns under rest and stress conditions is a useful non-invasive procedure for monitoring long-term patency and PTCA-results of this vessel. PMID- 11219595 TI - Enhanced methods for visualizing myocardial perfusion with peripheral venous injection of levovist: application of triggered harmonic imaging and triggered harmonic power Doppler imaging techniques. AB - OBJECTIVES: The purpose of this study was to determine whether triggered harmonic imaging (THI) or triggered harmonic power Doppler imaging (THPDI) could obtain the myocardial contrast enhancement using peripheral venous injection of a first generation echocardiographic contrast agent, Levovist. METHODS: In a phantom model, we examined the influence of an acoustic power, harmonic filters, transmitted frequencies and focus positions of transducer on Levovist. Then fundamental, harmonic or harmonic power Doppler imaging were performed with ECG triggered imaging in eight closed-chest dogs using bolus injection of Levovist. RESULTS: In a phantom model, the highest transmission power (Mechanical index 1.6), a medium harmonic filter and a focus position (6 cm) resulted in the best enhanced contrast in both THI and THPDI. Furthermore, higher pulse repetition frequency (5500 Hz) of harmonic power Doppler made clearer enhancement. In animal models, we could not observe the apparent myocardial contrast using triggered fundamental imaging, and the intensity of each region of interest (ROI) of myocardium had not changed significantly. However, homogeneous myocardial contrast could be obtained using THI, which was conditioned on the highest transmission power, a medium harmonic filter same as the phantom model, at a lower transmitted frequency (1.8 MHz) and a focus position, which were located in the middle portion of the left ventricle. The peak intensity of each ROI increased significantly in a gray level. Furthermore, THPDI caused emphasized myocardial contrast visually. CONCLUSIONS: These results indicate that THI and THPDI produce obvious MCE using peripheral venous injection of Levovist. PMID- 11219596 TI - Anatomical M-mode: A novel technique for the quantitative evaluation of regional wall motion analysis during dobutamine echocardiography. AB - Recognition of abnormal wall motion during dobutamine echocardiography requires an expert observer. Anatomical M-mode echocardiography may offer a novel quantitative approach to interpretation, amenable to less expert readers. We studied the application of this new modality to 124 patients (80 with known coronary anatomy and 44 patients at low probability of coronary disease) who underwent dobutamine echocardiography, using a standard protocol. Wall motion was interpreted by an experienced reader, using digitally stored 2-dimensional echocardiographic images at rest and peak stress. Percentage of systolic thickening was measured offline using anatomical M-mode echocardiography in the basal and mid segments at rest and peak dose, and compared with wall motion scores and coronary angiography. Of 729 segments, wall motion was identified as normal in 449, ischemic or viable in 171 and showed resting WM abnormalities only in 109 segments. After exclusion of the apex, anatomical M-mode measurements were feasible in 729 of 960 possible basal- and mid-zone segments (76%). Measurement of systolic thickening at peak dose was reproducible within (r2 = 0.83) and between observers (r2 = 0.93). Systolic thickening was significantly greater in segments with normal wall motion (37 +/- 2%) compared with ischemic or viable segments (30 +/- 2%, p < 0.001), and scar segments (23 +/- 3%, p < 0.001). There was an increment of thickening from rest to stress in normal and viable segments, no change in scar, and a decrement in ischemic segments. Significant coronary artery disease (defined by stenoses >70% diameter) was present in 59 patients. Systolic thickening showed significant variation between segments interpreted by wall motion scoring and angiography as true and false positive and true and false negative (p < 0.05). Measurement of systolic thickening using anatomical M-mode echocardiography offers an objective method to quantify systolic thickening at dobutamine echocardiography but has limited clinical feasibility. PMID- 11219597 TI - Comparison of methods of fractional area change for detection of regional left ventricular dysfunction. AB - Three methods for assessment of fractional area change (FAC) and conventional versus cross-sectional segmentation were compared under conditions known to occur frequently during stress echocardiography. Quantitative analysis of 80 echocardiograms obtained from healthy subjects, patients with left ventricular (LV) dysfunction and after coronary artery bypass grafting included segmental and cross-sectional FACs by the centroid method with fixed and floating reference and a method with floating external reference. All segmental and cross-sectional FACs were equally sensitive to LV dysfunction, and segmental FACs failed to accurately predict the location of coronary lesions. The centroid method with floating reference and cross-sectional FACs were the least affected by surgery induced intrathoracic heart motion. In moderate to severe LV dysfunction FAC by the centroid method with floating reference and cross sections were rarely within normal limits. Cross-sectional FACs may prove to be useful in stress echocardiography. For viability studies segmental FAC by fixed reference appears to be the method of choice. PMID- 11219599 TI - Laser to the heart in coronary artery disease. PMID- 11219598 TI - Evaluation of the long-term functional outcome assessed by myocardial perfusion scintigraphy following excimer laser angioplasty compared to balloon angioplasty in longer coronary lesions. AB - OBJECTIVES: Evaluation of the long-term functional outcome assessed by exercise myocardial perfusion imaging following excimer laser angioplasty compared to balloon angioplasty in coronary lesions > 10 mm in length. BACKGROUND: Previous randomized studies evaluating the effect of coronary interventions mainly focused on the long-term clinical and angiographic outcome. The functional outcome, assessed by myocardial perfusion scintigraphy, has not been evaluated in a randomized setting. METHODS: A total of 308 patients with stable angina and a longer coronary lesion (> 10 mm) were randomized to excimer laser angioplasty or balloon angioplasty. A 99mTechnetium-2-methoxy isobutyl isonitrile (MIBI) single photon emission computed tomography (SPECT) study was performed in 139 patients before the initial angioplasty procedure and at 6 months follow-up (73 patients in the laser group versus 66 patients in the balloon group, respectively). Exercise tolerance at follow-up was compared to baseline values by means of exercise duration and double product at peak exercise. Myocardial perfusion of the randomized vascular bed was assessed semi-quantitatively on the MIBI SPECT images. The reversible defects were graded as mild, moderate or severe. Myocardial perfusion at follow-up was expressed as a percentage reduction in incidence and grading of the reversible defects compared to baseline values. RESULTS: Forty-four (61%) patients assigned to laser angioplasty were asymptomatic at 6 months follow-up compared to 34 (52%) patients assigned to balloon angioplasty (p = NS). Improvement in exercise duration and double product were 0.7 +/- 2.1 min and 4.3 +/- 6.2 min/mmHg/l,000, respectively, in the laser group, versus 0.3 +/- 2.5 min and 3.1 +/- 5.5 min/mmHg/1,000, respectively, in the balloon group (both p = NS). The percentage reduction of reversible defects was 23% in patients assigned to laser angioplasty vs. 29% in patients assigned to balloon angioplasty (Relative risk [RR]: 0.79, 95% confidence interval [CI]: 0.40 1.57; p = 0.50). The mild, moderate and severe reversible defects improved in 44.4, 63.6 and 66.6%, respectively, in the laser angioplasty group vs. 66.6, 53.8 and 90%, respectively, in the balloon angioplasty group. None of the comparisons were significantly different. CONCLUSION: Excimer laser angioplasty compared to balloon angioplasty in coronary lesions > 10 mm in length yields a similar long term functional outcome assessed by anginal status, exercise tolerance and myocardial perfusion. PMID- 11219600 TI - Comparison between segmental wall motion and wall thickening in patients with coronary artery disease using quantitative gated SPECT software. AB - This study was performed to evaluate regional wall motion (WM) and wall thickening (WT) using gated myocardial perfusion single photon emission computed tomography (SPECT) and to determine their similarity and disparity in patients with coronary artery disease (CAD). A total of 44 patients underwent 1 day stress/rest (MIBI) gated SPECT. Commercially available quantitative analysis of gated SPECT (QGS) software was used to generate 3D surface display and cine-mode SPECT display. Left ventricle was divided into nine segments to score WM and WT from 0 (no abnormality) to 4 (severe abnormality) by six independent observers. Finally a mean score was calculated for each segment from the scores of six observers. There was fairly good correlation between WM and WT of individual segments (r = 0.62, p < 0.0001). Concordance rate (IWM - WTI < 1) was 85%. A large difference between WM and WT (WM - WT > or = 2) was observed in 15 segments, including 12 segments with greater WM abnormalities and 3 segments with greater WT abnormalities (lateral and inferior walls). Greater WM abnormalities were most commonly observed in anteroseptal segments especially in post coronary artery bypass grafting (CABG) patients. In conclusion, WM and WT showed similarity on QGS studies. However, these two parameters may be determined separately in gated SPECT studies for comprehensive and robust evaluation of the functional status of myocardium. Analyses based on WM assessment alone may lead to erroneous results especially in septal regions. PMID- 11219601 TI - A systematic analysis of factors which may impact upon tomographic perfusion imaging measurements: implications for the use of Tc-99m sestamibi in acute myocardial infarction. AB - BACKGROUND: The use of acute Tc-99m sestamibi imaging has provided a valuable methodology to assess myocardium at risk and collateral blood flow. OBJECTIVE: The purpose of this study was to determine the impact of physical, physiologic, and reconstruction factors on the extent and severity of Tc-99m sestamibi images in a porcine model of coronary occlusion and reperfusion. METHODS AND RESULTS: Eleven pigs underwent 40 min of coronary occlusion using a balloon catheter followed by reperfusion. Radiolabeled microspheres were injected during occlusion for blood flow determination and 20-30 mCi of Tc-99m sestamibi was injected intravenously for cardiac imaging. Each animal underwent four modes of gamma camera imaging: a cardiac and respiratory gated SPECT study, an ungated SPECT study, a post-mortem SPECT study and an ex-situ study where the heart was sliced into five short axis slices and directly imaged. All animals had extensive wall motion abnormalities at the time of imaging. Myocardial risk area by ex-situ imaging was 32 +/- 9% LV and did not significantly change with the addition of a chest cavity and tomographic reconstruction (post-mortem and gated imaging) or cardiac and respiratory motion (ungated imaging). Defect severity was significantly underestimated with the addition of a chest cavity and tomographic reconstruction but was unaltered by cardiac and respiratory motion. CONCLUSIONS: The assessment of risk area acutely by SPECT Tc-99m sestamibi imaging is unaffected by cardiac motion obviating the necessity for gated imaging. Estimated defect severity (which has been used as a measure of collateral flow) is significantly reduced by the chest wall and tomographic acquisition and reconstruction suggesting a role for scatter and attenuation algorithms for this measure. PMID- 11219602 TI - Eustachian valve mimicking a right atrial cystic tumor. AB - We report the case of a 65-year-old patient referred to our hospital for stroke. In the course of the diagnostic procedure, a transesophageal echocardiography was performed and showed at first sight a mass attached to the right aspect of the interatrial septum and mimicking a cystic tumor. But after performing multiple views, it was in fact demonstrated a large Eustachian valve with its extremity attached to the right aspect of the interatrial septum. The increasing use of transesophageal echocardiography to evaluate patients makes it important for echocardiographers to recognize this anatomic entity and its normal variants. PMID- 11219603 TI - Macromolecular dynamics in living cell nuclei revealed by fluorescence redistribution after photobleaching. AB - Regulation and structural requirements of vital nuclear processes such as DNA replication, transcription, RNA processing and DNA repair inside the eukaryote nucleus are as yet poorly understood. Although a wealth of evidence exists pointing to a considerable degree of spatial organisation of chromatin and nuclear processes, there are still questions concerning the dynamics and interaction of nuclear proteins that remain unanswered. The cloning of the gene encoding the green fluorescent protein (GFP) has revolutionised the study of proteins in living cells. The expression of recombinant cDNA fusion plasmids of GFP and proteins of interest currently enables the investigation of those proteins in living cells. Time-lapse confocal microscopy as well as quantitative fluorescence methods such as fluorescence redistribution after photobleaching (FRAP) and fluorescence resonance energy transfer are widely applied to living cells expressing GFP fusion proteins. This review gives an overview of the current state of knowledge of nuclear structure and function. In particular, the different applications of FRAP technology to study the dynamics of GFP-tagged nuclear proteins will be summarised. PMID- 11219605 TI - Methods for visualizing RNA processing and transport pathways in living cells. AB - Recent advances in fluorescence microscopy, imaging, and probe technology provided possibilities to study the spatial and temporal distribution of RNA species in living cells. While some methods have been developed to localize all nascent or poly (A) containing transcripts others have been developed to study the in vivo distribution of specific RNA species. Irrespective of the method that has been used, the results of these studies provided important information concerning the localization and the cellular transport pathways of RNAs. Also, the picture emerges that RNA molecules travel through the nucleus at much faster speed, equaling that of free diffusion, than previously anticipated. Still, a major challenge proves to be the development of a microscopic detection technique that allows specific, in vivo, detection of low levels of RNA species by fluorescence in situ hybridization, without interfering fluorescent background signals derived from non-hybridized probe sequences and autofluorescent cell components. By applying photoactivatable caged fluorochrome-, molecular beacon-, or fluorescence resonance energy transfer (FRET)-based detection methods an important step in the future of living cell analysis has already been made. PMID- 11219604 TI - Illuminating the human genome. AB - The identification and analysis of novel genes and their encoded protein products remains a vigorous area of research in biology today. Worldwide genomic and cDNA sequencing projects are now identifying new molecules every day and the need for methodologies to functionally characterise these proteins has never been greater. The distinct compartmental arrangement of eukaryotic cells helps define the processes which occur within or in proximity to these membranes, and as such provides one means of inferring protein function. We describe here some of the methods recently reported in the literature, which use the subcellular localisation of proteins as a first step towards their further characterisation. PMID- 11219606 TI - In vivo imaging of the mammalian nervous system using fluorescent proteins. AB - The recent development of fluorescent proteins has rapidly and radically altered the way cell biology is performed by allowing simple, non-invasive imaging of cellular processes in real time. The special properties of the nervous system, such as synaptic morphology, axonal/dendritic maturation, and neuronal migration are especially amenable to investigation using fluorescent proteins. This review focuses on the various genetic and viral vectors used to express fluorescent proteins in vivo and in slice culture, and the strengths and limitations associated with them. PMID- 11219607 TI - Long-term expression of foreign genes in normal human epidermal keratinocytes after transfection with lipid/DNA complexes. AB - Normal human epidermal keratinocytes were isolated and cultivated in serum-free medium. The expression of the integrin subunits alpha6 and beta1 indicated that a high number of keratinocytes from the stem cell system was present. These cells were transfected with complexes made of different cationic lipids and marker genes. Effectene showed a 20-fold higher transfection efficiency, compared to Lipofectin and Lipofectamine, and a similar low toxicity. The transfection protocol was optimised. A DNA/lipid ratio of 0.133 showed the highest transfection efficiency. Keratinocytes expressed the marker gene luciferase for 20 days. The maximum expression occurred after 3-4 days, where individual patches of fluorescent keratinocytes were detected. Transfected keratinocytes, cultivated at the air-liquid interface, expressed the marker gene beta-galactosidase for at least 7 weeks. PMID- 11219608 TI - The color of mice: in the light of GFP-variant reporters. AB - The mouse currently represents the premier model organism for mammalian genetic studies. Over the past decade the production of targeted and transgenic lines of mice has become commonplace, with current technology allowing the creation of mutations at base pair resolution. Such genome modifications are becoming increasingly elaborate and often incorporate gene-based reporters for tagging different cellular populations. Until recently, lacZ, the bacterial beta galactosidase gene has been the marker of choice for most studies in the mouse. However, over the past 3 years another valuable reporter has emerged, and its attractiveness is reflected by an explosion in its use in mice. Green fluorescent protein (GFP), a novel autofluorescent genetic reporter derived from the bioluminescent jellyfish Aequorea victoria, currently represents a unique alternative to other gene-based reporters in that its visualization is non invasive and so can be monitored in real-time in vitro or in vivo. It has the added advantage that it can be quantified by, for example, flow cytometry, confocal microscopy, and fluorometric assays. Several mutants of the original wild-type GFP gene that improve thermostability and fluorescence have been engineered. Enhanced GFP is one such variant, which has gained popularity for use in transgenic or targeted mice. Moreover, various GFP spectral variants have also been developed, and two of these novel color variants, enhanced yellow fluorescent protein (EYFP) and enhanced cyan fluorescent protein (ECFP), can also be used in mice. Since the spectral profiles of the ECFP and EYFP color variants are distinct and non-overlapping, these two reporters can be co-visualized, and are therefore ideal for in vivo double-labeling or fluorescent energy transfer analyses. The use of GFP and its color variants as reporters provides an unprecedented level of sophistication and represents the next step in mouse genome engineering technology by opening up the possibility of combinatorial non invasive reporter usage within a single animal. PMID- 11219609 TI - Green fluorescent protein (GFP) fusion constructs in gene therapy research. AB - The history of green fluorescent protein (GFP) as a marker is less than 10 years old, but it has already made a major impact on many areas of natural sciences, especially on cell biology and histochemistry. GFP can be detected in living cells without selection or staining and it can be fused to other proteins to yield fluorescent chimeras. The potential of GFP has also been recognised by gene therapy researchers and various GFP-tagged therapeutic proteins have been constructed. These chimeric proteins have been used to determine the expression level, site and time course of the therapeutic gene, or the correlation between gene transfer rate and therapeutic outcome. This review summarises the status of the applications of GFP fusions in gene therapy research. PMID- 11219611 TI - Cutaneous gene therapy--an update. AB - In this paper we review various strategies for gene transfer into the skin, their applications and show some of our own examples. The skin is the most accessible somatic tissue. Inherited skin diseases, such as epidermolysis bullosa and ichthyosis, and various systemic metabolic disorders are under investigation as potential candidate diseases for cutaneous gene transfer. Research is directed against genetic therapy of wounds and malignancies as well. So far, cutaneous gene transfer only has been used experimentally, but several clinical trials are under preparation. PMID- 11219610 TI - Tumor structure and extracellular matrix as a possible barrier for therapeutic approaches using immune cells or adenoviruses in colorectal cancer. AB - In this article we report about the role that tumor structure and extracellular matrix (ECM) may play in immunotherapy and in gene therapy using adenoviruses. We performed studies in a rat model for colorectal cancer, CC531, and in specimens of human colorectal cancer. The tumors were composed of two compartments, tumor cell nests surrounded by stromal cells. ECM proteins were expressed in the stromal part, where the blood vessels were also located. Furthermore, in several tumors, the tumor cell nests were surrounded by basal membrane-like structures. Therefore, in vascular approaches to treat cancer, therapeutic agents on their route to tumor cells may be hampered by ECM to reach tumor cells. We found that immune cells were abundantly present in tumors from colorectal origin. These cells were, however, not found in direct contact with tumor cells, but mainly in the stromal part of the tumor. Adenoviruses, when intravascularly injected, did not reach tumor cells in the CC531 rat model. Tumor cells were only infected, and even then in limited numbers, in cases of intratumoral injection. We hypothesize that ECM in a tumor is a barrier both for immune cells and for adenoviruses to make direct contact with these tumor cells, and thus limits colorectal tumor therapy. PMID- 11219613 TI - Outcomes after selective dorsal rhizotomy for spastic cerebral palsy. AB - OBJECT: The purpose of this article was to review the published outcomes after selective dorsal rhizotomy (SDR) for treatment of spastic cerebral palsy. METHODS: A literature search identified all articles related to outcomes after SDR. The outcomes were reviewed according to a paradigm developed by the National Center for Medical Rehabilitation Research (NCMRR). The quality of the evidence for each outcome was assessed using Sackett's criteria and the classification system developed by the Brain Trauma Foundation and the American Association of Neurological Surgeons. RESULTS: There is very strong evidence for benefits of SDR in the impairment domain of the NCMRR classification. SDR has been shown conclusively to decrease lower limb spasticity and increase lower limb range of motion. There is strong, but not as conclusive evidence that SDR has a positive impact in the functional limitation dimension, with improvements in motor function, and in particular the Gross Motor Function Assessment (GMFM). There is a moderate degree of certainty that SDR results in improvements in the disability dimension, as evidenced particularly by improvements in the Functional Independence Measure for Children (WeeFIM) and Pediatric Evaluation of Disability Inventory (PEDI). There is a moderate degree of certainty that SDR results in positive suprasegmental effects, especially related to upper limb function and cognition. There is weak evidence that SDR may reduce the need for orthopedic procedures in patients with spastic cerebral palsy, and the impact on hip subluxation relative to the natural history of this problem is unclear. CONCLUSIONS: This information could help to define the role of SDR in the management of the child with spastic cerebral palsy, in the light of alternative therapies, such as intrathecal baclofen and botulinum toxin, which have been introduced more recently. It also reveals the need for further studies, particularly dealing with quality of life and economic impact. PMID- 11219612 TI - Novel mutant Semliki Forest virus vectors: gene expression and localization studies in neuronal cells. AB - Semliki Forest virus vectors (SFV) are suitable for high-level transgene expression in neuronal tissue, both in vitro and in vivo. Cortical and hippocampal primary neurons in culture are efficiently infected resulting in 75 95% of GFP-positive cells, and injection of SFV vectors into hippocampal slice cultures revealed a highly neuron-specific expression pattern with more than 90% of the infected cells being neurons. Here, we present novel SFV vector mutants and describe their infection patterns obtained in cultures of baby hamster kidney (BHK) cells, dissociated hippocampal neurons, and organotypic hippocampal slices. A less cytotoxic vector SFV(PD), carrying two point mutations in the nsP2 gene, showed much higher GFP expression levels in primary hippocampal neurons compared to the wild-type SFV vector. A triple mutant vector SFV(PDE153) demonstrated a temperature-sensitive phenotype in both BHK cells and primary neurons. In hippocampal slices cultured at 36 degrees C, SFV(PDE153) showed a remarkably higher (ca 250-fold) preference for expression in interneurons rather than in pyramidal cells as compared to wild-type SFV. The quadruple mutant SFV(PDTE) led to substantially increased and prolonged GFP expression in primary neurons. Relative to SFV(PDE153), a more pronounced temperature-sensitive phenotype was found resulting in no virus production and no GFP expression at the non permissive temperature (36-37 degrees C) in BHK cells, in dissociated neurons, and in organotypic hippocampal slices. The described novel SFV vectors will be useful for several specific applications in neurobiology. PMID- 11219615 TI - Double ependymoma of the filum terminale. AB - Myxopapillary ependymoma of the filum terminale and conus medullaris are relatively common spinal intradural neoplasms in adults, only 8-14% affecting children. We describe a case of a 15-year-old girl with two myxopapillary ependymomas of the filum terminale. Although cases of two such tumours have been described in adults, we have not found any similar paediatric cases in the literature. PMID- 11219614 TI - Multicentric glioma with unusual clinical presentation. AB - Multiple glioma is a well-recognized but uncommon entity. They are grouped in two categories: multifocal and multicentric gliomas. Multifocal gliomas grow through dissemination along an established route, spreading through commissural pathways, CSF channels, or the blood or by local extension through satellite formation; at the opposite end of the spectrum, multicentric gliomas are widely separated lesions whose simultaneous presence cannot be attributed to any of the above pathways. Reports in the literature refer to single cases or small series of multicentric gliomas, almost always in adult patients, their occurrence in children being even less frequent. We report the case of a 12-year-old boy with multicentric glioma, atypical acute clinical onset and fast growth of three other tumors in 8 months, and then discuss the problems of diagnosis and therapy. PMID- 11219616 TI - Intramedullary spinal teratoma with spina bifida. AB - Spinal intramedullary teratoma is a rare tumor. We report a case of intramedullary teratoma of the conus medullaris with spina bifida. A 5-year-old boy was admitted to our hospital for removal of a lumbosacral tumor sited in an intramedullary location at the conus medullaris, which was totally resected with neuroendoscopic assistance. The pathological diagnosis was mature teratoma consisting of three germ cell layers. The pathogenesis of spinal intramedullary teratoma is discussed with special reference to spina bifida. PMID- 11219617 TI - Inadvertent insertion of a nasogastric tube in a patient with head trauma. AB - This is a report of a 3-year-old boy with intracranial penetration of a nasogastric tube causing brain damage in the left frontal lobe. A computed tomography (CT) showed passage of the nasogastric tube via a fracture of the cribriform plate into the intracranial cavity. The tube was manually removed under antibiotic prophylaxis. The patient then underwent dural repair for rinorrhoea and was discharged in good health. PMID- 11219618 TI - The curly tail mouse model of human neural tube defects demonstrates normal spinal cord differentiation at the level of the meningomyelocele: implications for fetal surgery. AB - The paralysis associated with lumbosacral meningomyelocele has been attributed both to myelodysplasia and to degeneration of the exposed neural tissue. Surgically created dysraphism shows that exposure of an intact spinal cord in a genetically normal animal results in degeneration of the normal nervous tissue and subsequent paralysis. Our objective was to study neuronal differentiation in the curly tail mouse mutant model, which develops lumbosacral meningomyelocele naturally and is a phenocopy of nonsyndromic human neural tube defects. Prenatal repair of meningomyelocele assumes that the normal neuronal differentiation program occurs despite failure of neurulation. Here we demonstrate that this most suitable animal model has normal differentiation of neuronal structures at the level of the meningomyelocele. TuJ1, an antibody to neuronal specific class III beta-tubulin, an early marker of neuronal differentiation, was used to stain paraffin-embedded sections of curly tail mouse embryo meningomyelocele. Embryos were examined at embryonic day 13.5 (E13.5). The inbred mouse strain, C57BL6/J, which is genetically similar to the curly tail mouse, was used as a control in these studies. We show that early neuronal differentiation appears intact within the meningomyelocele. TuJ stains structures within the open neural tube. Motor neurons are present in the ventral horn and ventral roots. Dorsal root ganglia are present and of similar size to controls. The staining pattern is similar to that seen in the C57BL/6J control mouse, although dorsal structures are laterally displaced in the curly tail meningomyelocele. Based on this model, fetal surgery to repair human meningomyelocele may preserve neurological function in those cases where there is not an inherent genetic defect of the neural tissue. PMID- 11219619 TI - Ependymoma in children and young adults (0-19 years): report of 25 consecutive cases. AB - The objective of this retrospective study was to evaluate the relative effect of surgery and radiotherapy (RT) on the survival of 25 consecutive children and young adults treated for ependymoma [18 in the posterior fossa (PF), 2 in supratentorial locations (ST) and 5 in intraspinal locations (IS)]. Five-year survival rates for patients with PF, ST and IS tumors were 28%, 0% and 100%, respectively. Total tumor resection was a positive prognostic factor in the case of PF tumors. No patients with subtotal removal of a PF tumor survived for longer than 5 years. The effect of RT on survival of patients with PF ependymomas in this series was uncertain. No patients with PF ependymoma had disseminated disease at diagnosis, and all tumor recurrences were local. Based on these observations, we see no indications for craniospinal RT of PF ependymomas, except in rare cases of disseminated disease. If RT is given, it should only be targeted to the tumor site. The two patients with ST ependymoma died within 3.8 years after primary treatment. Our series of ST ependymomas does not allow any specific treatment recommendations. One patient with IS ependymoma was cured by surgery alone. Four patients with IS ependymoma had documented residual tumor after surgery. RT induced remission in these patients. For IS ependymomas we recommend no RT if total tumor removal can be documented. In patients with subtotal removal of IS ependymomas local RT is effective and should be given. PMID- 11219620 TI - Cerebellar gliomas in infants: specificity, pathology, and outcome. AB - Cerebellar gliomas (CGs) in children are generally associated with a favorable outcome; however, data regarding these tumors in very young children are scarce. We report on our experience with CGs in children less than 3 years old at surgery, compared with a second group older than 3 years. From 1991 to 1996, we operated on 7 children with CGs in the first group and 43 in the second. Psychomotor delay and regression were the first symptoms in 3 cases, and 3 had macrocrania. The tumor was totally removed in all cases. One child died intraoperatively of air embolism and subdural bleeding. Three had malignant tumors (grade 3 or 4). There was no operative mortality or malignancy in the second group of patients. With a mean follow-up of 33 months, all survivors in the first group are disease-free, with no or minimal symptoms, and attend normal schools. The clinical, surgical, and pathological features suggest that children under 3 years of age represent a specific subgroup of CGs. PMID- 11219621 TI - Cerebral aneurysms in childhood. AB - OBJECTS: The aim of this work was to ascertain any clinical and anatomical factors allowing differentiation between aneurysms of childhood and those occurring in adults by comparing both groups. METHODS: Results obtained in a total of 17 children and adolescents aged up to 18 who had been operated on for cerebral aneurysm in our department from 1989 to 1997 (3% of all patients treated for subarachnoid haemorrhage resulting from ruptured cerebral aneurysm in this period) were compared with those in the adult group operated on in our department. In contrast to the situation in adults, there was a male predominance in our population. In children we found only 1 case of middle cerebral aneurysm and 1 case of multiple aneurysms. We also found a high rate of rebleeding in the paediatric group. CONCLUSIONS: We suggest that the very good outcome (100% very good results in patients operated on early) obtained and the high risk of rebleeding in children with cerebral aneurysm allow the recommendation of early surgery in children with ruptured cerebral aneurysms. PMID- 11219622 TI - Spontaneous regression of a symptomatic pineal cyst after endoscopic third ventriculostomy. AB - With the advent of modern diagnostic tools for neuroimaging, the incidental detection of pineal cysts in asymptomatic subjects has increased. Only rarely do pineal cysts present with the clinical signs and symptoms of increased intracranial pressure or with neurological deficits in relation to compression and distortion of the adjacent nervous structures and cerebrospinal fluid pathways. While asymptomatic cysts are considered to be normal variants for which no further investigations are usually required, surgical treatment is suggested for symptomatic cysts, with the goal of eliminating the block in the cerebrospinal fluid circulation and/or the mass effect exerted by the lesion. In this report we describe a pediatric case of symptomatic pineal cyst, revealed by repeated episodes of headache caused by secondary obstructive hydrocephalus. Following an endoscopic third-ventriculostomy, serial magnetic resonance imaging studies demonstrated that not only had the ventriculomegaly resolved but also that the pineal cyst had regressed over time. A to-and-fro movement of fluid through the cyst wall, the direction of which depends on the equilibrium existing between the inner pressure of the cyst and the outer cerebrospinal fluid pressure, is suggested as a possible mechanism accounting for this unexpected result--to our knowledge, the first reported in literature. PMID- 11219623 TI - Primary intervention for posthemorrhagic hydrocephalus in very low birthweight infants by ventriculostomy. AB - The objective of our study was to determine the efficacy of ventriculostomy as the primary treatment for posthemorrhagic hydrocephalus in premature infants. Within a period of 4 years, 20 very low birthweight (VLBW) infants (birthweight median 1,135 g, range 650-1,470 g) were treated for progressive posthemorrhagic hydrocephalus (PHHC) by right parietal ventriculostomy (Salmon Rickham) at a mean age of 21 days. Serial tapping of the subcutaneous reservoir was performed for temporary drainage until conversion to a permanent ventriculoperitoneal (VP) shunt or spontaneous resolution of hydrocephalus. A total of 1,402 punctures (median 71/infant, range 13-168) was performed. The results showed that only 1/20 patients developed a cerebrospinal fluid (CSF) infection, accounting for a 5% patient-related and 0.07% procedure-related infection rate. Major complications such as skin defects, subdural hygroma, or CSF leaks occurred in three patients (15%). A permanent shunt was needed in 17 patients (85%). We concluded that, as an effective alternative to serial or lumbar puncture, there should be early implantation of ventriculostomy reservoirs for serial taps to control intracranial pressure in PHHC of VLBW infants until a permanent shunt can be placed because of the low incidence of infections and technical complications. PMID- 11219624 TI - Pressure compensation in shunt-dependent hydrocephalus with CSF shunt malfunction. AB - This study is a retrospective analysis of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) data from 56 children with active hydrocephalus and cerebrospinal fluid (CSF) shunt malfunction. The pressures were measured from a separately sited CSF access device placed in the frontal horn of the lateral ventricle. Of the patients, 79% had an elevated ICP (mean 20+/-12 mmHg). A subgroup of patients demonstrated ten different forms of CSF-filled swelling. This group had significantly lower ICP recordings (P=0.000075) with a mean ICP of 8.5 mmHg compared with the remainder (22.9 mmHg). This pressure 'compensation' was because of additional nonphysiological accommodation of CSF volume. Overall the CPP was normal in 35% of cases despite normal ICP occurring in only 11% of cases. The CPPs were not significantly different in those with and without compensation. Measurement of ICP may not always be a reliable indicator of shunt malfunction in shunt-dependent children who present with compensatory CSF-filled spaces. PMID- 11219626 TI - Sagittal synostosis: results of surgical treatment in 210 patients. AB - From 1977 to 1996, 210 patients suffering from scaphocephaly, have been operated on in our institutions. The surgical technique depended on the patients age. Single wide sagittal synostectomy was performed in 155 babies aged less than 3 months, obtaining good cosmetic results. Patients older than 3 months needed more complex and aggressive procedures to achieve similar results. The conclusions is that sagittal suturectomy is the proper treatment in younger patients under 3 months of age, and that a greater effort must be made to diagnose and treat these patients early. PMID- 11219625 TI - Hyponatraemia in children with acute CNS disease: SIADH or cerebral salt wasting? AB - Hyponatraemia in patients with an acute central nervous system disease can be caused by two different mechanisms: (1) retention [corrected] of free water, i.e. the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and (2) excessive sodium retention [corrected], i.e., the cerebral salt wasting syndrome (CSW). Although the concept of CSW is well known in adult medicine, it is still not established in child neurology. We conducted a retrospective analysis of electrolyte disturbances in 195 children with various acute CNS diseases. In 20 children (10.3%) hyponatraemia with plasma sodium below 130 mmol/l was identified. On the basis of clinical and laboratory data 7 of these 20 children were diagnosed as having SIADH, and the other 9 children, as having CSW. Our data suggest that hyponatraemia attributable to CSW is at least as frequent in children as SIADH. Because of their different pathophysiological mechanisms, which require diametrically opposed therapeutic regimens, early differential diagnosis is mandatory if the correct treatment is to be given. PMID- 11219627 TI - Cervical disc prolapse in childhood associated with Klippel-Feil syndrome. AB - Klippel-Feil syndrome is characterized by a variable degree of congenital fusion of the cervical spine. It can exist in association with other mesodermal deformities affecting several systems. Symptomatic cervical disc prolapse in the context of the syndrome is well documented in young adults. We present a case of a 5-year-old girl with the syndrome, who presented with mild motor developmental delay and cervical cord compression from a prolapsed C3/4 intervertebral disc, seen on MR scan. She also had posterior elements fused from C-2 to C-4. She improved after cervical discectomy. The presence of degenerative disc disease at such a young age and at a level mechanically protected by posterior element fusion indicates a congenital primary defect, rather than mechanical stress fatigue. PMID- 11219628 TI - Seizure outcomes after anterior callosotomy in patients with posterior-dominant and with anterior-dominant epileptiform discharges. AB - OBJECTS: We wished to find whether there was any difference in the postoperative seizure outcome between patients with bisynchronous anterior-dominant and those with posterior-dominant EDs after anterior callosotomy. METHODS: Seizure outcomes after anterior callosotomy in 7 patients with bisynchronous posterior-dominant epileptiform discharges and in 54 patients with anterior-dominant seizures were compared. All 61 cases had been followed up for more than 2 years after operation. One patient (14.3%) had become seizure free. Two patients (28.6%) had more than 50% reduction in seizure frequency, but 4 patients (57.2%) showed no improvement at all. The percentage of cases with significant improvement (more than 50% reduction of seizure frequency) was 43% (3 in 7), which is lower than in the patients with bisynchronous anterior-dominant EDs (64.8%). CONCLUSIONS: Our preliminary results suggest that anterior partial callosotomy could still be helpful in cases with bisynchronous posterior-dominant epileptiform discharges but the prognosis may be less optimistic than for those with anteriorly located discharges. PMID- 11219629 TI - Hydrocephalus and epilepsy. AB - Since the introduction of ventriculo-atrial and/or ventriculo-peritoneal shunting for hydrocephalic patients, controversies have developed regarding the likelihood of epileptic seizures developing as a result of the shunting itself and/or its complications. On the other hand, hydrocephalus is not commonly recognized as a cause of seizures in general, although epilepsy is reported to be frequently associated with shunt-treated hydrocephalus, especially in children. Several authors have reported an increased risk of epileptic seizures after shunt placement, but the underlying mechanisms are still controversial. The insult to the brain at the time of ventricular catheter insertion, the presence of the shunt tube itself as a foreign body, the burr hole location, the number of shunt revisions after malfunction, associated infection, the etiology of hydrocephalus, and associated mental retardation are thought to be related to the risk of epilepsy. Age at the time of initial shunt placement also seems to be an important factor. Early shunting is a well-known determinant of risk in shunt obstruction, and children less than 2 years old are consequently at a higher risk of developing epilepsy than older ones. It is reported that antiepileptic drug treatment is not so reliable as might be expected. Conscientious and more sophisticated EEG recording in those children may be beneficial during follow-up. The incidence of seizures in shunted children is reported to be quite high, ranging from 20% to approximately 50%, so that neurosurgeons should pay more attention to the issue of epilepsy in hydrocephalic children. Although ventriculo extracranial shunts have been the standard treatment for hydrocephalus for decades, the long-term morbidity, including postshunt epileptic seizures, has to be taken seriously. The use of neuroendoscopic techniques when indicated may ameliorate this problem a great deal in the future. PMID- 11219630 TI - Application of finite element analysis in neurosurgery. AB - With the rapid development of computer equipment, approximation by analytical solutions has become popular in mathematical modeling. Finite element (FE) analysis uses numerical methods to solve problems with physical phenomena, and these can be applied to various geometrically complex materials, such as brain. The FE formulation can provide such diverse domains as heat conduction, torsion of elastic material, diffusion and fluid flow, and it can view different objects of study in the neurosurgical field. In this article, the various applications of FE methods are introduced to illustrate the usefulness of the technique and the link between the external biomechanical aspect and internal phenomena in brain research. PMID- 11219631 TI - Dermoid cyst in the posterior fossa accompanied by Klippel-Feil syndrome. AB - OBJECTS: Dermoid cysts accompanied by Klippel-Feil syndrome are uncommon, and the coincidence of these two rare diseases suggests an interesting idea about the pathogenesis of a dermoid cyst, which the authors consider with reference to an actual case. A posterior fossa dermoid cyst with dermal sinus and Klippel-Feil syndrome are reported in the same patient. A 23-year-old woman was admitted to hospital with progressive headaches. METHODS: Cervical radiography demonstrated C4-5 vertebral fusion, and magnetic resonance imaging revealed a large cystic mass in the midline of the posterior fossa. The cystic lesion was totally removed along with the accompanying dermal sinus. It was histopathologically diagnosed as a dermoid cyst. CONCLUSION: The rare coincidence of a dermoid cyst and Klippel Feil syndrome suggests the possibility that a disturbance in the mesoderm before the fourth week of gestation might play an important part in the causation of dermoid cyst. PMID- 11219632 TI - The sartorial specter of viscocanalostomy. PMID- 11219633 TI - Effect of timolol on anterior optic nerve blood flow in patients with primary open-angle glaucoma as assessed by the Heidelberg retina flowmeter. AB - PURPOSE: To evaluate the effect of 0.5% timolol maleate on the capillary circulation of the anterior optic nerve head in patients with primary open-angle glaucoma and to compare the results with those obtained in a healthy control group. PATIENTS AND METHODS: Twelve patients with nonprogressive glaucoma and 12 age- and sex-matched healthy volunteers were included in this prospective study. Optic nerve head perfusion was examined by the Heidelberg Retina Flowmeter (HRF) in both groups. A 3-week washout period preceded the baseline measurement in the glaucoma group, and ONH blood flow was assessed again after 3 weeks of bilateral topical timolol treatment and 2 hours after timolol application. RESULTS: Intraocular pressure decreased significantly with timolol (P < 0.001). The HRF flow values for patients with glaucoma were comparable to those for a control group at baseline (P = 0.25), 3 weeks after timolol therapy (P = 0.09), and 2 hours after timolol instillation (P = 0.15). The glaucoma group showed no statistically significant change in the HRF parameter flow as compared with baseline, either after 3 weeks of timolol treatment or 2 hours after timolol instillation (P = 0.40). The heart rate and arterial systolic and diastolic blood pressure values showed no alteration after timolol therapy. CONCLUSIONS: Patients with nonprogressive glaucoma seem not to have an altered optic nerve blood flow as assessed by the HRF, and timolol treatment does not seem to alter the latter blood flow parameter in such patients. PMID- 11219634 TI - Diurnal variation of episcleral venous pressure in healthy patients: a pilot study. AB - PURPOSE: To study diurnal episcleral venous pressure (EVP) and its relation to intraocular pressure (IOP) in healthy patients. The influences of supine position and lid closure on EVP were also studied. DESIGN: Experimental observational study. PARTICIPANTS AND METHODS: Twelve healthy patients with no eye disease had their IOP and EVP measured at 16h00, 22h00, 22h30, 06h00, 06h30, 09h00, 12h00, and 16h00. Measurements at 22h30, 06h00, and 06h30 were performed on supine patients, and the measurement at 06h00 was with the eye that had been closed for the whole night. In a second experiment, EVP was measured on patients who were lying supine from 22h30 to 16h00 with one eye closed during the day. MAIN OUTCOME MEASURES: Episcleral venous pressure and IOP at varying time points during a 24 hour period. RESULTS: Episcleral venous pressure was relatively constant throughout the day except for a slight reduction at 22h00. After lying down, the EVP increased by 3.6 mm Hg and remained increased as long as the patient remained in this position. Eyelid closure did not affect EVP. IOP measured with the Tono Pen closely followed the variations in EVP. CONCLUSION: Episcleral venous pressure remains relatively constant throughout the day. It increases in the supine position with a corresponding increase in IOP. Lid closure does not influence EVP or IOP. PMID- 11219635 TI - Caffeine and intraocular pressure in a Nigerian population. AB - PURPOSE: Caffeine is widely consumed as kola nuts and in other products in sub Saharan Africa. We examined the acute effect of caffeine on the intraocular pressures of healthy Nigerian volunteers between the ages of 20 and 27 years. METHODS: Intraocular pressure and blood pressure were measured 0, 30, 60, and 90 minutes after the ingestion of coffee by two groups of participants, namely the experimental (caffeinated coffee) and control (decaffeinated coffee) groups. RESULTS: The result showed that ingested caffeine increases intraocular pressure and that the elevation, though variable across patients, is sustained for several minutes. The mean increase across patients rises monotonically with the postingestion time and by almost 4 mm Hg. There was also a corresponding increase in systolic and diastolic blood pressure of the caffeinated group. There was relatively no change in intraocular pressure or blood pressure with time in the control group. The difference between both groups was statistically significant (P < 0.05). CONCLUSIONS: The results suggest the need for more glaucoma screenings and proper patient education, particularly in Nigerian populations in which the consumption of caffeine, contained in kola nuts and in other raw and processed products, is endemic and long-term. PMID- 11219636 TI - Intraocular pressure after homologous penetrating keratoplasty. AB - PURPOSE: To evaluate intraocular pressure (IOP) changes after homologous central penetrating keratoplasty in a noncomparative interventional case series. METHODS: The study included 245 patients undergoing homologous central penetrating keratoplasty for keratoconus (n = 77), herpetic corneal scars (n = 29), nonherpetic corneal scars (n = 46), Fuchs endothelial dystrophy (n = 24), and secondary corneal endothelial decompensation caused by preceding intraocular operations (n = 69). Mean follow-up time was 30.4 +/- 18.7 months (range, 12.1 111.6 months). The same surgeon operated on all patients, and a peripheral iridotomy was routinely performed. RESULTS: On the first postoperative day, IOP was significantly (P = 0.02) higher than that before keratoplasty. Taking the whole study group and taking the study groups separately, IOP measurements determined on the third postoperative day (P = 0.57), 1 week after surgery (P = 0.55), or later (P > 0.50) were not significantly different from the preoperative values. Eyes undergoing keratoplasty with cataract surgery and eyes undergoing keratoplasty without additional intraocular procedures did not vary significantly (P > 0.10) in IOP measurements. IOP did not differ significantly (P > 0.50) between eyes with an immunologic graft reaction (n = 29) and eyes without a reaction (n = 216). Acute angle-closure glaucoma was not detected in any of the patients. IOP measurements were statistically independent of suture type (P > 0.10), age (P > 0.05), preoperative and postoperative refractive error (P > 0.05), preoperative and postoperative corneal astigmatism (P > 0.10), preoperative and postoperative visual acuity (P > 0.10), diameter of graft and trephine (P > 0.15), and oversize of the graft (P > 0.50). Postoperative IOP measurements were significantly (P < 0.01) correlated with preoperative IOP values. CONCLUSIONS: In eyes with a peripheral iridotomy performed during surgery, homologous central penetrating keratoplasty usually does not markedly change IOP. The main risk factor for postoperatively increased IOP is increased IOP before surgery. PMID- 11219637 TI - Intraocular pressure and medication control after clear corneal phacoemulsification and AcrySof posterior chamber intraocular lens implantation in patients with filtering blebs. AB - PURPOSE: To determine whether clear corneal phacoemulsification and the implantation of a copolymer acrylic (AcrySof, Alcon, Fort Worth, TX) intraocular lens will maintain the intraocular pressure (IOP) and number of medications in patients with a previous filtering bleb. PATIENTS AND METHODS: This retrospective analysis included 69 consecutive patients with previous trabeculectomy who had a copolymer acrylic intraocular lens implanted during cataract surgery between 1995 and 1999 by a single surgeon (A.C.S.C.). RESULTS: Mean IOP significantly decreased from 26.03 mm Hg (range, 14.5-70 mm Hg; n = 69) before trabeculectomy to 13.58 +/- 3.98 mm Hg (range, 5-24 mm Hg; n = 69) before the cataract extraction. After cataract extraction, the mean IOP increased significantly by 1.49 mm Hg (n = 67; P = 0.0013), by 1.85 mm Hg (n = 57; P = 0.0005), and by 1.01 mm Hg (n = 67; P = 0.042) after 6 months, after 1 year, and at the patient's last appointment, respectively. When patients whose pressures were purposely increased during cataract surgery were not included (n = 5), the mean increase at the last appointment was not significantly increased (0.54 mm Hg; n = 62; P = 0.25). The average number of antiglaucoma medications decreased from 2.93 (range, 1-5; n = 69) before trabeculectomy to 0.36 (range, 0-2; n = 69) before cataract surgery. This mean decreased to 0.34 (range, 0-2; n = 67; P = 0.8366) 6 months after cataract surgery and increased to 0.49 (range, 0-3; n = 57; P = 0.1029) and 0.62 (range, 0-3; n = 67; P = 0.0006) after 1 year and at the last appointment, respectively. Of the total study population, two (2.9%) patients required additional glaucoma surgery and 14 (20.3%) patients required additional antiglaucoma medications as compared with their precataract levels. CONCLUSIONS: Clear corneal phacoemulsification and the implantation of a copolymer acrylic (AcrySof, Alcon) posterior chamber intraocular lens statistically increased the number of medications and IOP of patients in our study. These increases, although statistically significant, did not cause a clinically significant deterioration in IOP control. PMID- 11219638 TI - Intraocular and interocular symmetry in normal retinal capillary perfusion. AB - PURPOSE: To investigate retinal capillary perfusion in different areas of the posterior pole (intraocular symmetry) and to compare capillary perfusion between the right and left eyes (interocular symmetry). METHODS: The study consisted of 52 clinically healthy patients between the ages of 45 and 74 years. Good quality images were obtained in 30 patients. By using scanning laser Doppler flowmetry with the Heidelberg Retina Flowmeter, three 10 degree scans were obtained from the fovea and superior and inferior retina of the study eye (for intraocular symmetry) and from the fovea of the fellow eye (for interocular comparison). Values of volume, flow, and velocity were recorded from each of these areas. Repeated measures analysis of variance, with Bonferroni correction, was used for groupwise comparison between areas in the study eye. Paired t tests, with Bonferroni correction, were used to compare nonfoveolar perfusion between the right and left eyes for each patient. RESULTS: Capillary volume in the foveola was significantly less than that in areas superior and inferior and 3 degrees nasal and temporal, and it was found to increase with eccentricity in the macular region. Only 2 of 30 patients had significant interocular differences between the extrafoveolar areas. CONCLUSION: Significant differences in retinal capillary perfusion were found across the macular region and corresponded with the increase in capillary beds. The Heidelberg Retina Flowmeter also measured the expected decrease in volume at the foveolar avascular zone. There were no significant interocular differences in perfusion. Eye movements, media opacities, and poor tear film quality had a deleterious effect on image quality. PMID- 11219639 TI - Bleb window cryopexy for the management of oversized, misplaced blebs. AB - PURPOSE: To describe a new technique for revising oversized blebs after trabeculectomy. METHODS: A chart review of consecutive patients undergoing bleb window cryopexy was conducted. Patients with symptomatic oversized blebs were candidates for the technique, regardless of the intraocular pressure. Under topical anesthesia, the bleb was incised and a 3 mm x 3 mm conjunctival window was removed using 0.12 forceps and Vannas scissors. Light cryotherapy was applied to the sclera through the window. A soft bandage contact lens was then placed for compression, and a patch was applied. All patients were given antibiotic drops the first day after surgery. Topical corticosteroid drops were used to minimize postoperative inflammation. Outcome measures included relief of symptoms, adequate control of intraocular pressure, and restoration of filtering bleb function without further antiglaucoma medication or surgical bleb revision. RESULTS: Nine patients met the inclusion criteria. All patients had flattening of the bleb with symptomatic relief within 2 weeks. No loss of bleb function occurred. One patient developed aqueous misdirection after the procedure. CONCLUSION: Early results showed that bleb window cryopexy is safe and effective. This minimally invasive technique can be useful for selected patients with large. symptomatic, overhanging blebs. PMID- 11219640 TI - Silicone oil glaucoma. PMID- 11219641 TI - How does nonpenetrating glaucoma surgery work? Aqueous outflow resistance and glaucoma surgery. AB - Histologic, experimental, and theoretical studies of the aqueous outflow pathways point toward the juxtacanalicular region and inner wall of Schlemm's canal as the likely site of aqueous outflow resistance in the normal eye. At least 50% of the aqueous outflow resistance in the normal eye and the bulk of the pathologically increased resistance in the glaucomatous eye resides in the trabecular meshwork and the inner wall of Schlemm's canal. The uveoscleral, or uveovortex, pathway, which accounts for perhaps 10% of the aqueous drainage in the healthy aged human eye, can become a major accessory route for aqueous drainage after pharmacologic treatment. Surgeries designed to incise or remove the abnormal trabecular meshwork of glaucoma address the pathologic problem of the disease. Surgeries that unroof Schlemm's canal or expand the canal, such as viscocanalostomy, probably cause inadvertent ruptures of the inner wall and juxtacanalicular tissue, thus relieving the abnormal outflow resistance of glaucoma. This review is a summary of current thought on the pathophysiology of aqueous outflow resistance in glaucoma and, in light of this, provides an interpretation of the mechanism of pressure reduction created by these new surgeries. PMID- 11219643 TI - The sixth annual Optic Nerve Rescue and Regeneration Think Tank: developmental genetics in glaucoma. PMID- 11219642 TI - Retrograde infusion of fluorescein to confirm location and patency of a glaucoma drainage device. AB - BACKGROUND: During surgical revision of a glaucoma drainage device, the status of the implant tube can be in question. We report two cases in which retrograde infusion of fluorescein-stained balanced salt solution was used to confirm the patency and location of the tube. METHODS: Fluorescein-stained balanced salt solution was made by dipping a sterile fluorescein strip into a 3-mL syringe of balanced salt solution until the fluid was visibly yellow. A 30-gauge canula was inserted into the tube at the reservoir end, and fluorescein-stained balanced salt solution was infused into the eye. RESULTS: Retrograde infusion of fluorescein-stained balanced salt solution confirmed the location and patency of the glaucoma drainage device implant tube, obviating the need for more extensive surgical intervention in these two cases. Neither patient experienced an adverse event. CONCLUSION: Retrograde infusion of fluorescein-stained balanced salt solution is a useful adjunctive technique for surgical revision of glaucoma drainage devices. PMID- 11219644 TI - Sex differences on a computerized mental rotation task disappear with computer familiarization. AB - The area of cognitive research that has produced the most consistent sex differences is spatial ability. Particularly, men consistently perform better on mental rotation tasks than do women. This study examined the effects of familiarization with a computer on performance of a computerized two-dimensional mental rotation task. Two groups of college students (N=44) performed the rotation task, with one group performing a color-matching task that allowed them to be familiarized with the computer prior to the rotation task. Among the participants who only performed the rotation task, the 11 men performed better than the 11 women. Among the participants who performed the computer familiarization task before the rotation task, how ever, there were no sex differences on the mental rotation task between the 10 men and 12 women. These data indicate that sex differences on this two-dimensional task may reflect familiarization with the computer, not the mental rotation component of the task. Further research with larger samples and increased range of task difficulty is encouraged. PMID- 11219645 TI - Quality of life of people with epilepsy following temporal lobectomy: a preliminary report. AB - This is a preliminary report of the quality of life of 9 people, 5 men and 4 women, in Hong Kong who underwent temporal lobectomy for seizure control. The Chinese version of World Health Organization Quality of Life Measure Abbreviated Version, validated in Hong Kong, was used as the outcome measure. Analysis suggested that the quality of life of these participants after successful temporal lobectomy was poorer than that of 157 healthy controls in the physical and psychological domains as measured. This suggests that other factors in addition to achieving complete seizure control play significant roles in promoting the quality of life of such patients. PMID- 11219646 TI - A psychometric investigation of the Clinical Instruction Analysis Tool--Athletic Training II. AB - To identify clinical instructors', students', and patients' behaviors during athletic training clinical education, the Clinical Instruction Analysis Tool Athletic Training II was developed and used by two trained observers to assess interobserver agreement, which was 95.4%. PMID- 11219648 TI - Effects of hypnosis on flow states and golf performance. AB - This study examined the effects of an hypnotic intervention on flow states and golf-chipping performance of 3 participants. The study utilized an ideographic ABA single-subject design combined with a procedure to assess the participants' internal experience (Wollman, 1986). The intervention involved relaxation, imagery, hypnotic induction, hypnotic regression, and trigger control procedures over 5 wk. and 7 trials. Analysis indicated the 3 participants increased their mean golf-chipping performance from the trials in Baseline 1 to intervention, with 2 returning to Baseline 1 performance after the intervention phase at Baseline 2. The intensity of flow experienced by the participants during the performance trials was measured using Jackson and Marsh's 1996 Flow State Scale. Two participants experienced higher flow during the intervention phase and much lower flow during Baselines 1 and 2. Finally, participants indicated the intervention seemed useful in keeping them confident, relaxed, and in control. These results support the hypothesis that an hypnotic intervention can improve golf-chipping performance and increase feelings and cognitions associated with flow. PMID- 11219647 TI - Comparison of eye-movement patterns in schizophrenic and normal adults during examination of facial affect displays. AB - Patients with schizophrenia are known to have deficits in facial affect recognition. Subjects were 25 schizophrenic patients and 25 normal subjects who were shown pairs of slides of laughing faces and asked to compare the intensity of laughter in the two slides. Eye movements were recorded using an infrared scleral reflection technique. Normal subjects efficiently compared the same facial features in the two slides, examining the eyes and mouth, important areas for recognizing laughter, for a longer time than other regions of the face. Schizophrenic patients spent less time ex amining the eyes and mouth and often examined other regions of the face or areas other than the face. Similar results were obtained for the number of fixation points. That schizophrenic patients may have employed an inefficient strategy with few effective eye movements in facial comparison and recognition may help to explain the deficits in facial recognition observed in schizophrenic patients. PMID- 11219649 TI - Relationship between attentional orientation and associative learning. AB - This study presents experimental evidence for a relationship between attentional orientation and associative learning. Learning to establish contingencies between warning signals and subsequent task stimuli is a phenomenon which we know from previous studies to be more associated with the left hemisphere. We investigated how hemispheric priming, i.e., activating one hemisphere by directing attention towards the contralateral hemispace, affected both the rate and the extent of associative and nonassociative learning. When attention was directed towards the right while perceiving a discrimination task stimulus, the rate of learning through contingency formation was increased since the relative activation of the left hemisphere was increased. Such a relationship was not found for relative activation of the right hemisphere following leftward orientation of attention. PMID- 11219650 TI - Sidedness preference as an index of organization of laterality. AB - A rightward bias to all forms of sidedness seems to be particularly human and perhaps characteristic of every human society. However, this phenomenon has been studied mainly in relation to lateralization of handedness and language. This study investigated the consistency of right- and nonright-handed individuals in prefer ring the same side for foot, eye, and ear using Coren's Lateral Preference Inventory. The sample of 194 students, 91 boys and 103 girls, ranging in age from 11.5-14.5 years (M age 13.2 yr.) was recruited from public junior high schools in a rural area in Greece on the island of Rhodes. Despite the dominance of the right side observed in handedness, footedness, eyedness, and earedness, this tendency was not equally strong in all four indexes of lateral preference, with handedness showing comparatively the strongest tendency and earedness showing comparatively the weakest tendency. Moreover, the strength of preference for the same side for foot, eye, and ear was significantly weaker in nonright-handed individuals compared to right handed individuals. These results agree with the hypothesis that nonright-handers may have reduced rath er than reversed asymmetry. PMID- 11219651 TI - Random number generation deficit in schizophrenia characterized by oral vs written response modes. AB - To characterize the deficit in random number generation in schizophrenia with respect to control of sensory information processing, the present study employed a random number generation task using 10 digits (0 to 9) and compared two response modes (oral and written) with different amounts of sensory availability about the previous choices of the subject. Analysis indicated that the increased availability of previous information in the written response mode may exacerbate an aspect of the deficit in random number generation in schizophrenia reflecting the disturbance in control of sensory information processing. The comparison of performance in written and oral response modes may be useful in assessing schizophrenic psychopathology. PMID- 11219652 TI - Manipulations of sensory information: a test of the hypothesis of redundancy of knowledge of results. AB - The hypothesis of redundancy in knowledge of results was examined by manipulating the amount and location of sensory information available to participants performing a coincident anticipation timing task. Either the last 8 lights or the last 16 lights of the visual display were visible to 48 participants. Following an acquisition phase, learning was tested over immediate (5-min.) and delayed (24 hr.) retention intervals. The main finding was that performance was better when knowledge of results was present, regardless of the amount of sensory information available; therefore, knowledge of results was not redundant information for learning this task. PMID- 11219653 TI - Psychological factors and sex differences in acceptance of monovision. AB - 49 participants, adapted to using contact lenses, completed a battery of psychological tests to examine differences between persons who were successful in wearing monovision lenses for presbyopia and those who were unsuccessful. Although visual performance and requirements strongly affect participants' satisfaction with monovision lenses, personality characteristics and visual processing styles appear to in fluence the percentage of full-time wear. Of the participants, 41% (20 of 49) ultimately rejected monovision for a variety of both visual and psychological reasons. Sex differences were evidenced in the psychological variables correlated to monovision lens wear. Analysis indicated that men scoring as introverts rejected monovision while women with difficulty perceiving a visual pattern against visual background noise had difficulty adapting to monovision and exhibited shorter wearing times. PMID- 11219654 TI - A comparison of predictions and data for a model of two automatic responses in stimulus-response compatibility. AB - Effects of stimulus-response compatibility and position of hands have previously been reported to be additive or interactive. It has been assumed in a recent model that, in some particular experimental paradigms, the presentation of the stimulus would activate two automatic responses. In the present study three theoretical limit cases of this model are investigated. The different sets of experimental data are consistent with the predicted values. PMID- 11219655 TI - Relations of empathy and social responsibility to guilt feelings among undergraduate students. AB - Empathy and social responsibility as related to guilt feelings were investigated among undergraduate students. Subjects (337 men and 353 women) were assessed for guilt feelings, empathy, and social responsibility. The Guilt Inventory was used to assess guilt feelings. Analysis indicated that scores on the two empathy subscales, Fantasy and Personal Distress, were related to rated Trait Guilt and State Guilt, whereas Social Responsibility scores were associated with those on Moral Stan dards of the Guilt Inventory. PMID- 11219656 TI - Parental attribution of artistic ability in talented children. AB - Attributed talent is a powerful construct that can have important consequences for the lives of children. Parents and schools often provide special programs to support talented children, and attributed talent can influence children's behavior. The purpose of this study was to examine how the parents of children in a program for gifted and talented students explain the artistic capabilities of their children. Analysis indicated parents attributed the artistic capabilities of the children primarily to innate talent and intrinsic motivation. However, estimates of accumulated hours of involvement in art showed that the children had similar patterns of involve ment in art as did individuals with strong records of achievement in other domains. Alternative explanations for achievement, including deliberate practice theory, are discussed. PMID- 11219657 TI - Automatic auditory processing and event-related brain potentials in persons with mental retardation. AB - Measuring event-related brain potentials, this study examined automatic auditory processing in adults with and without mental retardation. Using an auditory oddball paradigm under an inattentive condition, we anticipated that an enhanced negative potential would be followed by a relatively small positive potential. The former was considered as the mismatch negativity and the latter as the P3a. Retarded adults (1 woman, 6 men, defined as a range of moderate to profound retardation) and 8 nonretarded (2 women, 6 men) adults participated. The mismatch negativity showed smaller amplitudes and greater latencies for retarded persons than those for nonretarded adults, whereas the P3a for the groups was comparable. The results may suggest malfunction of automatic auditory change-detection of the brain in mentally retarded persons. PMID- 11219658 TI - Study of anticipatory postural adjustments in an air pistol-shooting task. AB - A segmental teleokinetic movement performed from an upright standing position is usually preceded by a sequence of postural movements having the goal of counteracting the imbalance which will be caused by the forthcoming movement. This study had two aims, (1) to verify whether the postural component was programmed in the same way as that of the teleokinetic component and (2) to verify whether the postural component was specific to the direction and speed of the movement. 12 participants performed a pistol-shooting task involving a rapid arm-raising movement. Three directions, two time deadlines, and three types of cue were manipulated. This study showed that the postural component was sensitive to the cue effects, the characteristics of anticipatory postural adjustments were specific to the direction of the movement, and the characteristics of the postural muscle EMG burst were the same whether the participants programmed or deprogrammed and reprogrammed their movements for a given direction. The speed parameter did not seem to have any significant influence on the characteristics of the anticipatory postural adjustments. PMID- 11219659 TI - Visual search for single and combined features by children and adults: possible developmental inferences. AB - Visual search time was measured in four groups of children 4 to 10 years of age and in young adults, as a function of display size for both target present and target-absent conditions. The slopes of regression lines in a simple search (search for ? within /) were compared with those obtained in within-dimension conjunction target searches, within either homogeneous (search for the inverted T within Ts) or heterogeneous distractors (search for arrow within Ys and inverted Ys). Analysis indicated that simple search was always preattentive (slopes near 0) after 5 years of age and serial (with positive slopes) before this age. Searching within heterogeneous distractors apparently involved element-by-element scrutiny and focal attention in all groups whereas searching within homogeneous distractors required distributed attention, perhaps based on parallel grouping of distractors in adults, though distractors were focally attended to by children. PMID- 11219660 TI - Sex and skill differences in translation of English color words by Chinese students. AB - The present study investigated sex and skill differences in color-word translation by Chinese-speaking students in university English classes. A questionnaire was administered to estimate the correlation between subjects' performance and their color-related hobbies. To conceptualize the issue better, two more groups of correlated parameter (academic achievements plus demographic factors) were introduced in this research as well. 40 English majors (20 women, 20 men), ranging in education from level one to level four, were randomly drawn from a metropolitan university and tested in the experiments as subjects. These university students were asked to provide Chinese equivalents for a list of 33 elaborated English color terms chosen from a thesaurus by mapping on the 11 color tone categories defined by basic color theory. The results confirm the findings in relevant studies that used native speakers as subjects by observing that (1) women possessed a richer color vocabulary both in their source language and in their target language, (2) women also provided more elaborated Chinese equivalents to the color words used as stimuli, and finally, (3) women showed a superiority in accuracy in this color-lexicon matching or translating task. As a whole, the effects of skill and age were not significant. A significant correlation was found between the learners' proficiency in English and performance in translation of color words, but this relationship was rather weak and only true for the men. Color-related hobbies did not significantly correlate with the color-decoding performance of these language learners. Neither did the demographic factors. Taken together, it is sensible to state that differences reported here were affected primarily by the sex of the learn er. conditionally by language proficiency, and presumably by the cognitive and perceptual sex differences as well. These findings further indicate that the process of color codability is a complicated but unstudied issue in language learning and that sex should be treated as an independent variable in this area of research. PMID- 11219661 TI - Self-perception of breath odor: role of body image and psychopathologic traits. AB - Oral malodor is a common complaint in Western society and is an important reason why adults seek dental counsel. In the present study, an attempt was made to evaluate the contribution of psychopathologic traits and of body-image char acteristics on participants' self-perception of breath odor. 60 participants without any specific complaint concerning breath odor (55% men: M age 35.5 yr., SD= 10) were evaluated. Variables included self-evaluation of participants' own breath odor (gener ally and current), an organoleptic evaluation of an impartial judge of odor, measurement of the volatile sulfide level in the oral cavity, and questionnaires referring to psychopathologic symptoms and body-image characteristics. Stepwise regression analysis showed that in addition to impartial measurements, self-perception of breath odor among noncomplaining subjects can be predicted by their feelings and attitudes toward the body and by their hostility. PMID- 11219662 TI - The tau and anti-tau effects in successively presented stimuli. AB - It was confirmed by the reproduction method with 20 adults that (a) the tau effect, i.e., the greater the temporal separation between successively presented stimuli with a constant spatial interval, the greater the apparent spatial interval, occurred, especially in the situation in which the participants were assumed to form a set easily using temporal interval as the cue for spatial interval estimation, and (b) the anti-tau effect occurred in the special situation in which the participants were assumed to form a set using speed of an imaginary movement as the cue for it. These findings supported the hypothesis of "cue-selection sets." PMID- 11219663 TI - Examination of force-production properties during static explosive grip based on force-time curve parameters. AB - The present study attempts to clarify the properties of force-time curves in the force-development phase during static explosive grip exertion and to determine force-time parameters in relation to static explosive strength. 80 healthy young males (age 17.8 +/- 2.5 yr.) exerted maximal isometric force as fast and forcefully as possible. In total, 21 variables, e.g., time to fixed level, integrated area, average force, integrated area to fixed time, force at the maximal rate of force development, and maximal rate of force development, were selected as force-time parameters. Good reliability was obtained for average force in force levels above 90% of maximal strength (.64-.93), integrated area to a fixed time of 1.0-2.0 sec. (.86-.93), force at the maximal rate of force development (.67), and maximal rate of force development (.73). In addition, these values correlated closely with maximal grip strength (r= .65-.93). Further, significant differences in maximal grip strength, average force in force levels above 90% of maximal strength, integrated area to fixed time, and force at the maximal rate of force development were found among three groups categorized by average force in force levels of maximal strength. These results suggested that individual differences were present in the force-time curve patterns during the force-development phase of static explosive grip exertion and that the average force in force levels of maximal strength might be a valuable tool for evaluating static explosive strength. PMID- 11219664 TI - Field dependence and verbalized strategies on the portable rod-and-frame test by depressed outpatients and normal controls. AB - This study examined the relationships between scores on the cognitive style of field dependence-independence and verbalized strategies on the Portable Rod-and Frame Test for normal and psychopathological outpatients. We attempted to verify (a) Manning's hypothesis (1991) of a correspondence between scores on field dependence and external strategies (reference to the visual field) and scores on field independence and internal strategies (reference to the body) on perceptual tasks, and (b) a tendency of depressed persons to score as field dependent, and (c) use of external verbalized strategies. A total of 50 depressed outpatients and 50 normal controls were administered the test and requested to report the strategy they had employed to solve the problem. Contrary to Manning's findings, no significant relationship was found between cognitive style and verbalized strategies in the total sample. Depressed outpatients classified as internal scored significantly higher on the Group Embedded Figures Test but appeared more field dependent on the Rod-and-Frame Test. Moreover, only for the former test did depressed outpatients score more field-dependent than controls. Finally, no significant relationship was found between the diagnosis of depression and use of external strategies; however, field dependence and the use of external strategies on the Rod-and-Frame Test were associated with more severe depressive symptoms measured by the D scale of the MMPI-2. Further research is needed to assess the role of premorbid personality structures of depression in subjective and objective aspects of Rod-and-Frame Test performance. PMID- 11219665 TI - Changes in eye-head-body movements during maze learning. AB - Investigation of the relationship between visual search (eye movement) and walking (head and body movement) during way-finding through a maze by each of 6 subject pedestrians who wore an eye camera showed patterns of sight lin, head movement, body movement, and changes of coordination between eye-head-body movement during the process of comprehension of the pathways were revealed. PMID- 11219666 TI - Factor structure and internal consistency of the Greek version of the Flow State Scale. AB - The present study tested the internal consistency and the factor struc ture of a translated version of the Flow State Scale with Greek sport participants. Sport psychology literature is not conclusive regarding sex differences and the type of sport in flow. The sample was comprised of 144 women from interactive sports (volleyball and handball) who were drawn from the second division of the first national category. Athletes completed the scale immediately after a game. Values of Cronbach alpha were used to estimate the internal consistency of the scale and confirmatory factor analysis to examine the model. The results showed acceptable psychometric prop erties of the scale and suggest a need for improvement of the problematic items. PMID- 11219667 TI - Training in lingual awareness during production of isolated syllables of English. AB - The purpose of this preliminary investigation was to determine the effects of training on lingual awareness during the production of isolated syllables of English. 60 subjects were selected for this investigation. They were placed into two groups of 30 individuals each. Group one (Trained) consisted of individuals who had received training in articulation and phonetics (M age=22.7) Group two (Untrained) consisted of individuals who had not received training in articulation and phonetics (M age= 18.8). The subjects in the Trained group were majors in speech-language pathology. The procedure involved asking subjects to imitate the production of a syllable, then describe where the tongue was located during that production. Following this request, subjects were given four multiple choice questions to answer regarding (a) tongue height (high to low), (b) tongue position (front to back), (c) contact with the teeth, and (d) contact with other structures within the oral cavity. Mean scores ranged from 1.87 to 3.2 (on a scale of 4.0) for the group of Trained subjects versus 1.5 to 2.4 for the Untrained subjects. The Trained subjects had significantly higher test scores on all phonemes (p<.05) with the exception of r and sh (p>.05). For both groups of subjects, the phonemes, r, sh, and l, were the most difficult to describe, while the phoneme t was described most accurately. PMID- 11219668 TI - Formation and decomposition of chloroaromatic compounds in chlorine-containing benzene/oxygen flames. AB - Premixed chlorine-containing, fuel-rich, low-pressure benzene/oxygen flames were analysed for the formation of (oxygenated) chloroaromatic compounds and their radicals by means of the condensation/radical-scavenging method (Hausmann, M., Homann, K.-H., 1995. Ber. Busenges. Phys. Chem. 99, 853-862). Several chlorinated organic compounds (methyl chloride, t-butyl chloride, chlorobenzene, chloroform) were used as additives within a maximum concentration of 10% of total fuel. Product identification and quantification were performed by GC/MS. The extent of formation of chloroaromatic compounds in these flames was largest in the cases of chlorobenzene and chloroform as additives. For chlorobenzene, 12 different chloroaromatics could be analysed in between C7H7Cl and C12H9Cl. Their formation is mainly due to conversion of initial chlorobenzene into substituted or oxidised derivatives, or growth products. Additional chlorination of aromatics is shown to be of minor importance in chlorobenzene-containing flames. Three isomeric (o/m/p) scavenging products could be identified for the chlorophenyl radical. In the chloroform case, 15 chloroaromatics could be analysed in between C6H5Cl and C14H9Cl. The weak C-Cl bond in chloroform is responsible for the high extent of chloroaromatics formation, either by Cl abstraction from the additive or by chlorination reactions via Cl radicals. Additionally, specific pathways to (di)chloroaromatics and chlorinated fulvene-type structures are outlined via CHCl2 and CCl2 radicals. PMID- 11219669 TI - Flamelet modeling of NO formation in laminar and turbulent diffusion flames. AB - The applicability of the laminar flamelet concept for the formation and destruction of nitric oxides in laminar and turbulent diffusion flames has been studied. In a first step, temperatures and species concentrations in an axisymmetric laminar diffusion flame have been calculated (i) by solving the detailed conservation equations and (ii) by applying the laminar flamelet concept. The main purpose of this step was the identification of differences between results from both approaches. It turned out that for highly temperature sensitive or relatively slow chemical processes, the inclusion of the full range of the prevailing scalar dissipation rates plays a major role for the calculated species concentrations. This behavior is obvious from the concept of the laminar flamelet model, where the scalar dissipation rate can be discussed in terms of the reciprocal of a residence time for attaining chemical equilibrium. In a second step, flamelet modeling of NOx formation was extended to a turbulent hydrogen diffusion flame. In both the steps, the flow fields of the flames were calculated by solving the Navier-Stokes equations in axisymmetric formulation using the SIMPLER algorithm. For the turbulent flow, Favre-averaged equations have been used and turbulence was modeled with the standard k-epsilon model including a correction term for axisymmetric systems. The averaging of the species concentrations was accomplished with presumed shape probability density functions (pdfs). The pdf of the mixture fraction was described with a beta function whereas that of the scalar dissipation rate was assumed to be log normal. Buoyancy effects have been taken into account. The calculated temperatures and concentrations were compared with data from different experiments. PMID- 11219670 TI - A modeling evaluation of the effect of chlorine on the formation of particulate matter in combustion. AB - The effect of chlorine on the fuel-rich oxidation of hydrocarbons and on the molecular weight growth of aromatics is analyzed by simulating experiments featuring a model chlorinated additive CH3Cl in a jet-stirred/plug-flow reactor and premixed flames. The kinetic model used in this work emphasizes the role of resonantly stabilized radicals in the formation and growth of aromatics, and considers soot inception as the net effect of molecular weight growth and graphitization of aromatic structures. Chlorinated hydrocarbons decompose at temperatures significantly lower than hydrocarbons, producing reactive Cl-atoms, which have a strong tendency to go to HCl. The HCI, tying up the H-atoms, inhibits hydrocarbon oxidation. The model is able to predict not only the levels but the shape of the experiments quite well and also the surprising finding of an increased soot formation associated with lower PAH levels found in rich flames with significant levels of chlorine. Based on reaction kinetic analysis, chlorine addition to the fuel enhances soot formation by promoting the formation of aromatic-ring compounds and accelerating the abstraction of aromatic H-atoms from stable PAH molecules. This process activates the transformation of aromatics to soot. PMID- 11219671 TI - Health risk of combustion products: toxicological considerations. AB - Combustion of organic material produces an almost uncountable number of products among which are many chemicals known to have toxic properties. A pertinent example is the diesel engine emission. There is concern about the possible health effects and we would like to know what risk is associated with the exposure. If risk is defined as the probability that a certain health effect occurs within a defined time span or as a result of a certain strain (Royal Society Study Group)- and it is important to emphasize the quantitative aspect of this definition--we must admit that we do not know a good answer. The example of diesel exhaust is used to demonstrate the toxicological approach to risk characterization in general and the possible improvement of exposure assessment with nitroarenes as indicators for environmental contaminations in particular. PMID- 11219672 TI - A flexible and stable numerical method for simulating the thermal decomposition of wood particles. AB - The objective of this paper is to present a flexible and stable simulation method to predict the thermal conversion of wood particles. A combination of several subprocesses such as heating-up, drying, pyrolysis, gasification and combustion of fuel particles of different properties and sizes represents the global process of thermal conversion. This approach allows for simultaneous processes e.g. reactions in time and covers the entire range between transport-limited (shrinking core) and kinetically limited (reacting core) reaction regimes. Thus, the model is applicable to simulate sufficiently accurate the thermal decomposition of each particle in a packed bed, of which the entire conversion is regarded as the sum of all particle processes. Effects such as fragmentation, swelling, homogeneous reactions e.g. ignition outside a particle are excluded as a tradeoff between complexity and calculation time. However, a description of the particle processes by one-dimensional and transient differential conservation equations for mass and energy is feasible to represent the above mentioned subprocesses. The particles are coupled to the gas phase by heat and mass transfer taking into account the Stefan correction due to the gas outflow during conversion. A general formulation of the conservation equations allows the geometry of a fuel particle to be treated as a plate, cylinder or sphere. In order to achieve a high degree of flexibility, the method distinguishes between data, such as kinetics or material properties and the conversion process, for which relevant data are stored in a data base for easy access and extension. The resulting modules of this subdivision are encapsulated into separate software units cast in a hierarchy of well-defined classes in Tools of Object-oriented Software for Continuum-Mechanics Applications (TOSCA) by object-oriented techniques. PMID- 11219673 TI - Nitrogen oxides from waste incineration: control by selective non-catalytic reduction. AB - An experimental study of the selective non-catalytic reduction (SNCR) process was carried out to determine the efficiency of NOx removal and NH3 mass balance, the NOx reducing reagent used. Experimental tests were conducted on a full-scale SNCR system installed in a hospital waste incineration plant. Anhydrous NH3 was injected at the boiler entrance for NOx removal. Ammonia was analyzed after each flue-gas treatment unit in order to establish its mass balance and NH3 slip in the stack gas was monitored as well. The effective fraction of NH3 for the thermal NOx reduction was calculated from measured values of injected and residual NH3. Results show that a NOx reduction efficiency in the range of 46.7 76.7% is possible at a NH3/NO molar ratio of 0.9-1.5. The fraction of NH3 used in NOx removal was found to decrease with rising NH3/NO molar ratio. The NH3 slip in the stack gas was very low, below permitted limits, even at the higher NH3 dosages used. No direct correlation was found between the NH3/NO molar ratio and the NH3 slip in the stack gas since the major part of the residual NH3 was converted into ammonium salts in the dry scrubbing reactor and subsequently collected in the fabric filter. Moreover, another fraction of NH3 was dissolved in the scrubbing liquor. PMID- 11219674 TI - Hazardous air pollutants formation from reactions of raw meal organics in cement kilns. AB - Thermally induced chlorination, condensation, and formation reactions of raw meal organic surrogates were investigated on different types of surfaces. The System for Thermal Diagnostic Studies provided a powerful tool to study these reactions under defined reaction conditions, which were related to typical conditions in the preheater zone of cement kiln. Experiments were conducted with benzene and benzene/myristic acid (C6H6/C13H27COOH) mixtures in a quartz reactor containing different chlorinating catalysts/reagents over a temperature range of 300-500 degrees C. Reaction products were trapped in-line and analyzed by GC-MS. A mixture of chlorides of calcium, potassium, aluminium and iron was highly effective for chlorination/condensation reactions of benzene and benzene/myristic acid mix at temperatures above 300 degrees C. The same behavior was observed only when calcium chloride and potassium chloride were used as chlorinating catalyst/reagent. This result showed that transition metal chlorides like FeCl3 are not necessary for chlorination/condensation of organics under post-combustion conditions. Methylene chloride was the major chlorinated product followed by chloroform and various other C1, C2 and C6 chlorinated products. Yields of chlorinated aliphatics were highest at 400 degrees C for both benzene and benzene/myristic acid mix. C6 products were mainly mono- to hexa-chlorinated benzenes with trace amounts of chlorinated phenols. The major chlorinated products observed in this study (i.e., methylene chloride, chloroform, chloroethanes and monochlorobenzene) were also present as major chlorinated hydrocarbons in the cement kiln field emission data. PMID- 11219675 TI - Identification of surrogate compounds for the emission of PCdd/F (I-TEQ value) and evaluation of their on-line real-time detectability in flue gases of waste incineration plants by REMPI-TOFMS mass spectrometry. AB - Correlations between products of incomplete combustion (PIC), e.g., chloroaromatic compounds, can be used to characterise the emissions from combustion processes, like municipal or hazardous waste incineration. A possible application of such relationships may be the on-line real-time monitoring of a characteristic surrogate, e.g., with Resonance-Enhanced Multiphoton Ionization Time-of-Flight Mass Spectrometry (REMPI-TOFMS). In this paper, we report the relationships of homologues and individual congeners of chlorinated benzenes (PCBz), dibenzo-p-dioxins (PCDD), dibenzofurans (PCDF) and phenols (PCPh) to the International Toxicity Equivalent (I-TEQ) of the PCDD/F (I-TEQ value) in the flue gas and stack gas of a 22 MW hazardous waste incinerator (HWI). As the REMPI detection sensitivity is decreasing with the increase of the degree of chlorination, this study focuses on the lower chlorinated species of the compounds mentioned above. Lower chlorinated species, e.g., chlorobenzene (MCBz), 1,4-dichlorobenzene, 2,4,6-trichlorodibenzofuran or 2,4-dichlorophenol, were identified as I-TEQ surrogates in the flue gas. In contrast to the higher chlorinated phenols, the lower chlorinated phenols (degree of chlorination <4) were not reliable as surrogates in the stack gas. The identified surrogates are evaluated in terms of their detectability by REMPI-TOFMS laser mass spectrometry. The outcome is that MCBz is the best suited surrogate for (indirect) on-line measuring of the I-TEQ value in the flue gas by REMPI-TOFMS. The correlation coefficient r of the MCBz concentration to the I-TEQ in the flue gas was 0.85. PMID- 11219676 TI - Combustion of brominated flame retardants and behavior of its byproducts. AB - The substance flow rate of PBDDs/DFs into flue gas and incineration residues from incineration of three types of waste samples containing brominated flame retardants were examined. The samples used consisted of PBDEs (a typical retardant), used TV casing materials (actual waste materials), and waste printed circuit boards. PBDDs/DFs concentrations in the experimental samples of PBDEs/PE, waste TV casing materials and printed circuit boards ranged between 3000 and 130,000 ng/g. These values are very high when compared to other investigations. The increase of chlorine concentration in input sample reduced the ratio of PBDDs/DFs in flue gas and raised the ratio of PCDDs/DFs. With adequate combustion control and flue gas treatment, the amount of PBDDs/DFs released from the incineration of resin containing brominated flame retardants was lower than the input amount. The presence of PBDDs/DFs in incineration residues dominated the total amount of dioxins released. When PBDDs/DFs, PCDDs/DFs and PXDDs/DFs were considered as a total, the total amount released was lower than the total amount input. PMID- 11219677 TI - Fate of antimony in municipal solid waste incineration. AB - The average antimony concentration in municipal solid waste is estimated to be about 10-60 ppm. Thermodynamical models predict a volatile behavior for antimony compounds, yet literature mass balances show that about 50% of the antimony input remains in the grate ashes. This fact can be explained by the formation of thermally stable antimonates in the fuel bed due to interactions with alkali or earth-alkali metals. Thermogravimetric experiments revealed an increased thermal stability for antimony oxide in presence of oxygen and calcium oxide. Spiking experiments on the test incinerator TAMARA showed that chlorination processes have a strong effect on antimony volatilization whereas high fuel-bed temperatures and addition of antimony oxide only have a moderate effect. In the grate ashes, antimony shows a pH-depending leaching property, which is typical for anionic species. This fact supports the thesis that antimony is present in the grate ashes in an anionic speciation. PMID- 11219678 TI - Reduction of combustion by-products in WTE plants: O2 enrichment of underfire air in the MARTIN SYNCOM process. AB - The SYNCOM process involves oxygen enrichment of underfire air, recirculation of flue gas and a combustion control system using infrared thermography of the waste layer on the grate. At the demonstration plant in Coburg, operational reliability and plant availability using SYNCOM could be proven under real disposal conditions with a waste throughput of 7 t/h. Oxygen enrichment of the underfire air promotes the destruction of pollutants due to the high oxygen partial pressures and temperatures. This is then reflected in very low residual amounts of organic combustion by-products in the bottom ash and flue gas from the SYNCOM unit. The flue gas concentrations of organic pollutants are reduced, as compared with conventional operation, by over 35% (for CO, total hydrocarbons and PCDD/F) at the boiler outlet. As the flue gas flow is reduced by oxygen enrichment and flue gas recirculation, the resulting reduction in terms of kg of pollutant per Mg of waste is even higher. In the bottom ash, the level of organic residues is reduced, by 45% in the case of loss on ignition and by 55% in the case of TOC and dioxins (I-TE of PCDD/F). This is due to the higher oxygen partial pressures and the fuel bed temperature which is increased by 135 to 1200 degrees C. Other important features of the process include more intense sintering and thus improved immobilization of the bottom ash, as well as reduced flue gas and fly ash flows. PMID- 11219679 TI - Comparison of dioxin-like-response in vitro and chemical analysis of emissions and materials. AB - Samples from industrial and domestic emissions and materials were investigated by using in vitro assays for dioxin-like-response (DLR) and chemical analysis. The results show a small part of persistent bioaccumulative toxicants (PBT) to be responsive in vitro. Clean-up procedures directed to persistence decrease the amount of inducing toxicants substantially. The comparison of biological in vitro (B) and chemical (A) analysis show ratios between B and A below 10 for DLR of persistent inductors. The consideration of PAH improved the knowledge about unknown less persistent agonists. PMID- 11219680 TI - Transient puffs of trace organic emissions from a batch-fed waste propellant incinerator. AB - Emissions data have been obtained from a waste propellant incinerator. The incinerator is a dual fixed hearth, controlled air incinerator equipped with acid gas and particulate scrubbing. "Puffing" has been evident in this waste propellant incinerator by spikes in the CO concentration. Transient puffs of organics may travel down the combustion chambers and lead to stack emissions. The major conclusions from this study are that (1) transient puffs are formed due to the semi-batch feed nature of the combustion process (causing a local oxygen deficiency) and high water content of the desensitized propellant; (2) in batch fed combustors, puffs can contribute to most of the organic emissions (which are relatively low) measured with US EPA sampling and analytical methods; (3) it is estimated that batch-fed combustion contributes up to 7-18 times more emissions than steady-state combustion will generate; (4) by applying dispersion analyses to determine the amount of oxygen deficiency in the flame zone, the combustion zone concentration of CO during batch-fed operation could be as high as 160,000 ppm, compared to a measured peak stack concentration of 1200 ppm CO; and (5) an organic sample is collected and averaged over at least a 2-h period that smooths out the transient peaks of organics emissions during batch-fed operation. For emissions that are associated with long-term potential health impacts, this is an appropriate sampling method. However, if a compound has a short-term potential health impact, it may be important to measure the time-resolved emissions of the compound. PMID- 11219681 TI - Kinetic studies of the reaction of hydroxyl radicals with trichloroethylene and tetrachloroethylene. AB - Rate coefficients are reported for the gas-phase reaction of the hydroxyl radical (OH) with C2HCl3 (k(1)) and C2Cl4 (k2) over an extended temperature range at 740+/-10 Torr in a He bath gas. These absolute rate measurements were accomplished using a laser photolysis/laser-induced fluorescence (LP/LIF) technique under slow flow conditions. The simple Arrhenius equation adequately describes the low temperature data for k1 (<650 K) and the entire data set for k2 and is given by (in units of cm3 molecule(-1) s(-1)): k1(291 - 650 K) = (9.73+/ 1.15) x 10(-13) exp (158.7+/-44.0)/T, k2(293 - 720 K ) = (1.53+/-0.14) x 10(-12) exp (-688.2+/-67.5)/T. Error limits are 2sigma values. The room temperature values for k1 and k2 are within +/-2sigma of previous data using different techniques. The Arrhenius activation energies for k1 and k2 are a factor of 2-3 lower than previously reported values. The experimental measurements for both k1 and k2 in conjunction with transition state and variation transition state theory calculations infer an OH addition mechanism. The lack of a measurable kinetic isotope effect for k1 is consistent with this mechanism. Insight into the subsequent reactions of the chemically activated intermediate are presented in the form of potential energy diagrams derived from ab initio calculations. PMID- 11219682 TI - The role of copper(II) chloride in the formation of organic chlorine in fly ash. AB - In the de-novo synthesis and formation of PCDD/PCDF, the transfer of inorganic chlorine to the carbonaceous material of fly ash plays an important role. Here, copper acts as a catalyst in the chlorination reaction. In experiments in the range of 250-350 degrees C under helium, we determined the stoichiometry of the chlorination reaction with model systems. Therefore, it was necessary to develop a method to quantify the copper(II) and copper(I) ions. In a combination of solid electron paramagnetic (spin) resonance spectroscopy (EPR) for Cu(I), and X-ray fluorescence spectroscopy (XRFA) analysis for Cu (total), we found a way for the quantification of copper(I) and (II). With these experiments, we can show that the chlorination reaction is relatively fast and comes to a stop under helium, after the copper(II) is reduced. The ratio between the organic chlorine formed and copper(II) reduced is, at the end of the reaction, 0.5, which is in agreement with the following reaction: 2CuCl2 + R-H-->2CuCl + R-Cl + HCl. PMID- 11219684 TI - Thermal destruction of benzene. AB - The thermal destruction of benzene in methane/air flue gas is studied experimentally using an atmospheric laminar flow reactor in laboratory scale. The reactor is operated at four different fuel equivalent ratios (phi = 0.06, 0.1,0.5, 3.7), and temperatures in the range from 850 to 973 K and realises a residence time of 5 s. Stable-species concentrations are measured by gas chromatography (GC) and high-pressure liquid chromatography (HPLC), where phenol, acetylene, formaldehyde, acrolein, methane and acetaldehyde are the major hydrocarbon products besides CO and CO2. The augmentation of the temperature from 850 to 973 K increases the benzene conversion rate from 55% to 99%. The experimental results for one fuel equivalent ratio (phi = 0.5) are compared to the benzene model proposed by Emdee et al. (J. Phys. Chem. 92 (1992) 2151-2161). A fair agreement is observed for the benzene consumption and the CO production throughout the temperature range considered here. The small hydrocarbons are not very well matched, which requires further research on the sub-models. Our experimental results on laboratory scale provide a database for the modelling of benzene oxidation in waste incinerators. PMID- 11219683 TI - Formate species in the low-temperature oxidation of dimethyl ether. AB - The oxidation of dimethyl ether (DME, 340 ppm in 10% O2) has been studied experimentally in an atmospheric pressure laminar flow reactor in the temperature range from 240 degrees C to 700 degrees C for residence times in the range 2-4 s. The influence of nitric oxide additions up to 620 ppm to the feed gases has also been investigated. Products of reaction were determined by FTIR. In the absence of NO, reaction is first detected at about 260 degrees C. The products in the low temperature region include formaldehyde (HCHO), and formic acid (HCOOH). The addition of NO leads to the appearance of methyl formate (CH3OCHO). While the overall behaviour of the system can be explained qualitatively in terms of typical low-temperature hydrocarbon ignition, recently published chemical kinetic models for DME ignition do not allow for the formation of these formate species. We find no experimental evidence for the formation of hydroperoxymethyl formate (HPMF, HOOCH2OCHO) which is predicted by the models to be a significant stable intermediate at temperatures below 350 degrees C. Since both formic acid and methyl formate have potentially harmful health effects, these observations may have significant implications for use of DME as a diesel fuel. PMID- 11219685 TI - Main products and kinetics of the thermal degradation of polyamides. AB - The thermal degradation of the polyamides (PA) 6, 12, 66 and 612 was investigated by means of thermal analysis/mass spectrometry (TA-MS) and pyrolysis in a german standard oven. Sample masses were about 20 and 40 mg. The heating rates used in the dynamic studies were 1, 5 and 10 K min(-1). Both air and nitrogen atmospheres were utilized. The kinetic parameters were calculated from the TA-MS measurements and the main decomposition products were registered online. The evolved products from the pyrolysis oven were captured and analyzed off-line by GC/MS. PMID- 11219686 TI - Numerical studies of the heterogeneous combustion of char using detailed chemistry. AB - The oxidation of graphite is used as a model system for the combustion of char. In order to understand this oxidation process a stagnation-point flow of an oxygen stream on a graphite surface is investigated numerically. The chemical reactions in the gas phase as well as on the surface are modelled by a series of elementary steps. The surface reactions take into consideration the different surface complexes formed, the influence of the geometry of the graphite surface and the interaction of gas-phase molecules with surface complexes. The rate coefficients used are estimated by applying methods of the microkinetic analysis of heterogeneous catalytic reactions. The mechanism is used to simulate the combustion rate of a graphite surface and the ratio of CO to CO2 formed on the surface. The simulation results are compared with experimental data and a good agreement is achieved. Furthermore, the fraction of char-bound nitrogen converted to N2 and N2O is calculated. PMID- 11219687 TI - Removal of dioxins and related aromatic hydrocarbons from flue gas streams by adsorption and catalytic destruction. AB - The dioxin removing capacity of the shell dedioxin system (SDDS-a Ti/V oxidative type catalyst) has been tested using the Umea lab-scale incinerator over the temperature range 100-230 degrees C and at space velocities of 8000 and 40,000 h( 1). Other analogous organic compounds, such as PCBs, PAHs, chlorobenzenes and chlorophenols have also been investigated. Results show a high degree of dioxin removal already at 100 degrees C (82%), which occurs mainly by adsorption. When the temperature is raised a transition towards destruction is seen and at 150 degrees C, gas hour space velocity (GHSV) 8000 and at 230 degrees C, GHSV 40,000 virtually all removal is by destruction. High PCDD/F destruction efficiencies are reported (> 99.9%, based on I-TEQ); the other dioxin-related species and PAHs are also removed and destroyed to a significant extent. The SDDS has proved to be an effective means of destroying organic compounds in the gas phase, particularly dioxins, at temperatures as low as 150 degrees C. PMID- 11219688 TI - Aromatic hydrocarbon growth from indene. AB - Aromatic hydrocarbon growth from indene (C9H8), which contains the five-membered ring cyclopentadienyl moiety, was investigated experimentally in a 4 s flow reactor over a temperature range 650-850 degrees C. Major products observed were three C18H12 isomers (chrysene, benz[a]anthracene and benzo[c]phenanthrene), two C17H12 isomers (benzo[a]fluorene and benzo[b]fluorene), and two C10H8 isomers (naphthalene and benzofulvene). Reaction pathways to these products are proposed. Indenyl radical addition to indene produces a resonance-stabilized radical intermediate which further reacts by one of two routes. Rearrangement by intramolecular addition produces a bridged structure that leads to the formation of C17H12 and C10H8 products. Alternatively, beta scission produces biindenyl, which leads to the formation of C18H12 products by a ring condensation mechanism analogous to that proposed for cyclopentadiene-to-naphthalene conversion. Temperature dependencies of both the partitioning between these two routes and the product isomer distributions are consistent with thermochemical modeling using semi-empirical molecular orbital methods. The results further illustrate the role of resonance-stabilized radical rearrangement in aromatic growth and condensation of systems with cyclopentadienyl moieties. PMID- 11219689 TI - A detailed numerical study of the evolution of soot particle size distributions in laminar premixed flames. AB - In this work, two numerical techniques, viz. the method of moments and a discrete h-p-Galerkin method, have been applied for numerical simulation of soot formation in a laminar premixed acetylene/oxygen/argon flame. From the evolution of the PAH and the soot particle size distributions, new insight into the different processes of soot formation is provided. For this, the single submodels have been examined with respect to their influence on the PAH and the soot particle size distributions. The particle inception step was studied in detail by comparing the simulated PAH size distributions with experimental results. Additionally, an estimation of the interaction energy of layered PAH dimers was performed by quantum chemical calculations. From these results, some evidence for the particle inception model employing coalescence of PAH molecules has been found. The numerical results for the gas phase chemical species, the particle number densities and volume fractions of soot as well as for the soot particle size distributions are compared with experimental data. Thereby, the consistency of the entire model is demonstrated. PMID- 11219690 TI - Investigation of soot by two-colour four-wave mixing. AB - A novel technique has been used for the temporally resolved investigation of the interaction of laser radiation and soot in a flame. Based on established soot vaporisation models we developed a framework to calculate the two-colour four wave mixing signal obtained in an acetylene/air diffusion flame at atmospheric pressure. The signal comprises a contribution due to soot and, depending on the wavelength of the probe laser, a contribution because of C2, which is generated by vaporising soot. For both parts of the signal we found a good agreement between measured and calculated power dependency. Furthermore, we measured spatial profiles of the signal in a Wolfhard-Parker slot burner. By analysing the different signal contributions we found that depending on the location within the flame there are particles with different C2 yield. PMID- 11219692 TI - Characterization of biomass pyrolysis vapors with molecular beam, single photon ionization time-of-flight mass spectrometry. AB - A single photon ionization, molecular beam sampling, reflectron time-of-flight mass spectrometer (SPI/MBTOFMS) has been developed and used to study pyrolysis products from a selection of biomass materials. Spectra are characterized by high resolution and decreased fragmentation compared to electron-impact ionization mass spectra from related molecular beam mass spectrometer systems equipped with quadrupole mass analyzers. PMID- 11219691 TI - Excimer laser fragmentation-fluorescence spectroscopy as a method for monitoring ammonium nitrate and ammonium sulfate particles. AB - Excimer laser fragmentation-fluorescence spectroscopy (ELFFS) is shown to be an effective detection strategy for ammonium nitrate and ammonium sulfate particles at atmospheric pressure and room temperature. Following photofragmentation of the ammonium salt particle, fluorescence of the NH fragment is observed at 336 nm. The fluorescence signal is shown to depend linearly on particle surface area for laser intensities varying from 1.2 x 10(8) to 6 x 10(8) W/cm2. The 100 shot (1 s) detection limits for ammonium nitrate range from 20 ppb for 0.2 microm particles to 125 ppb for 0.8 microm particles, where these concentrations are expressed as moles of ammonium ion per mole of air. For ammonium sulfate, the 100 shot (1 s) detection limits vary from 60 ppb for 0.2 microm particles to 500 ppb for 1 microm particles. These detection limits are low enough to measure ammonium salt particles that form in the exhaust of combustion processes utilizing ammonia injection as a nitric oxide control strategy. PMID- 11219693 TI - UV-visible spectroscopy of organic carbon particulate sampled from ethylene/air flames. AB - A systematic comparison of spectra obtained with extra and in situ diagnostics in the soot preinception region of rich, premixed ethylene air flames suggests that combustion generated organic carbon (OC) particulate can be extracted from flames and isolated from other flame material for further chemical analysis. Both the trend with height above the burner and the form of UV fluorescence and absorption spectra from extra situ sampled material captured in water agree with those measured in situ. These results show that the OC particulate formed in flames is partially water soluble. However, the collection efficiency can be increased using less polar solvents, like acetonitrile and dichloromethane. The fluorescence spectra from the water samples are comprised both a naphthalene-like component and a broad band UV fluorescence component similar to that observed in situ which is attributed to flame generated OC particulate. The broad band UV fluorescence centered around 320 nm is also observed very early in flames and does not change considerably with increasing flame residence time. These results support previous hypotheses that the UV broad band fluorescence is from carbonaceous material comprised two-ring aromatics, formed earlier than soot in the flame, and is still present along with soot at higher heights or flame residence times. PMID- 11219694 TI - Semi-volatile and particulate emissions from the combustion of alternative diesel fuels. AB - Motor vehicle emissions are a major anthropogenic source of air pollution and contribute to the deterioration of urban air quality. In this paper, we report results of a laboratory investigation of particle formation from four different alternative diesel fuels, namely, compressed natural gas (CNG), dimethyl ether (DME), biodiesel, and diesel, under fuel-rich conditions in the temperature range of 800-1200 degrees C at pressures of approximately 24 atm. A single pulse shock tube was used to simulate compression ignition (CI) combustion conditions. Gaseous fuels (CNG and DME) were exposed premixed in air while liquid fuels (diesel and biodiesel) were injected using a high-pressure liquid injector. The results of surface analysis using a scanning electron microscope showed that the particles formed from combustion of all four of the above-mentioned fuels had a mean diameter less than 0.1 microm. From results of gravimetric analysis and fuel injection size it was found that under the test conditions described above the relative particulate yields from CNG, DME, biodiesel, and diesel were 0.30%. 0.026%, 0.52%, and 0.51%, respectively. Chemical analysis of particles showed that DME combustion particles had the highest soluble organic fraction (SOF) at 71%, followed by biodiesel (66%), CNG (38%) and diesel (20%). This illustrates that in case of both gaseous and liquid fuels, oxygenated fuels have a higher SOF than non-oxygenated fuels. PMID- 11219695 TI - On-line real-time measurements at incineration plants: PAHs and a PCDD/F surrogate compound at stationary combustion conditions and during transient emission puffs. AB - Laser mass spectrometry has been applied for on-line monitoring of traces of aromatic compounds from flue gas of incineration plants. The experiments have been carried out at two sampling sites in an industrial hazardous-waste incinerator. With laser mass spectrometry resonance-enhanced multiphoton ionization (REMPI) with time-of-flight mass spectrometry (TOFMS) (REMPI-TOFMS), using the group selective multi-component monitoring approach, aromatic compounds are selectively ionized from the complex flue-gas matrix. In this case, the result of an REMPI-TOFMS on-line measurement is a distinct pattern of aromatic compounds. These patterns are dependent on: (i) the point of measurement, (ii) the incineration plant, (iii) the temperature, and (iv) the fuel. This contribution focuses on the fuel dependence of the pattern. The most transient behavior can be observed when containers filled with hazardous waste are burnt, leading to puffs. Real-time monitoring results of puffs are given. Furthermore, as an approach towards on-line monitoring of the TEQ (PCDD/F toxicity equivalent), REMPI-TOFMS on-line analysis results of chlorobenzene are presented. PMID- 11219696 TI - Reactions of 2,4,6-trichlorophenol on model fly ash: oxidation to CO and CO2, condensation to PCDD/F and conversion into related compounds. AB - Thermal treatment of 2,4,6-trichlorophenol on a magnesium silicate-based model fly ash in the temperature range between 250 degrees C and 400 degrees C leads predominantly to carbon monoxide and carbon dioxide. The fraction of 2,4,6 trichlorophenol which is oxidized to CO and CO2 increases from 3% at 250 degrees C to 75% at 400 degrees C. Further products are polychlorinated benzenes, dibenzo p-dioxins, dibenzofurans and phenols. The homologue and isomer patterns of the chlorobenzenes suggest chlorination in the ipso-position of the trichlorophenol. The formation of PCDD from 2,4,6-trichlorophenol and 2,3,4,6-tetrachlorophenol on municipal solid waste incinerator fly ashes and model fly ash were compared and the reaction order calculated. PMID- 11219697 TI - An experimental and numerical study of the thermal oxidation of chlorobenzene. AB - A combustion-driven flow reactor was used to examine the formation of chlorinated and non-chlorinated species from the thermal oxidation of chlorobenzene under post-flame conditions. Temperature varied from 725 to 1000 K, while the equivalence ratio was held constant at 0.5. Significant quantities of chlorinated intermediates, vinyl chloride and chlorophenol, were measured. A dominant C-Cl scission destruction pathway seen in pyrolytic studies was not observed. Instead, hydrogen-abstraction reactions prevailed, leading to high concentrations of chlorinated byproducts. The thermal oxidation of benzene was also investigated for comparison. Chemical kinetic modeling of benzene and chlorobenzene was used to explore reaction pathways. Two chlorobenzene models were developed to test the hypothesis that chlorobenzene oxidation follows a CO-expulsion breakdown pathway similar to that of benzene. For the temperatures and equivalence ratio studied, hydrogen abstraction by hydroxyl radicals dominates the initial destruction of both benzene and chlorobenzene. Chlorinated byproducts (i.e., chlorophenol and vinyl chloride) were formed from chlorobenzene oxidation in similar quantities and at similar temperatures to their respective analogue formed during benzene oxidation (i.e., phenol and ethylene). PMID- 11219698 TI - Temperature dependence of DCDD/F isomer distributions from chlorophenol precursors. AB - The temperature dependence of the gas-phase, rate-limited formation of dichlorodibenzo-p-dioxin (DCDD) and dichlorodibenzofuran (DCDF) isomers from 2,6 dichlorophenol and 3-chlorophenol, respectively, has been studied experimentally in an isothermal flow reactor over the range 300-900 degrees C under pyrolytic, oxidative and catalytic conditions and computationally using semi-empirical molecular orbital methods. At high temperatures, distributions of sets of DCDD/F condensation products are consistent with the calculated thermodynamic distributions, indicating that the relative rates of formation are governed by differences in symmetry and steric hindrance present in the isomer product structures. At low temperatures, however, this is not the case. In the case of 1,6- and 1,9-DCDD formed from 2, 6-dichlorophenol via Smiles rearrangement, the 1,6 isomer is favored at low temperatures more than thermodynamically predicted. This result appears to be consistent with kinetic effects of either the expansion of the five-membered ring Smiles intermediate or a lower activation energy six membered ring intermediate pathway that produces only the 1,6 isomer. For formation of 1,7-, 3,7- and 1,9-DCDF from 3-chlorophenol, the 1,7 isomer fraction increases at low temperatures whereas thermodynamics predicts a decrease. This result can be attributed to steric effects in alternative "sandwich-type" approach geometries of phenoxy radicals to form the o,o'-dihydroxybiphenyl (DOHB) intermediate via its keto-tautomers. Higher level molecular theory (ab initio) is needed to provide a more quantitative description of these kinetics. PMID- 11219699 TI - Dioxins from thermal and metallurgical processes: recent studies for the iron and steel industry. AB - In thermal metallurgical processes such as iron ore sintering and metal smelting operations, large flows of off-gases are generated. Mainly due to residue recycling in such processes, chlorine and volatile organics are always present in the feed. As a consequence of "de novo" formation, the off-gases from such processes typically contain dioxins in the range 0.3-30 ng I-TEQ/Nm3. So far there are only very few studies about the mechanisms of dioxin formation and destruction in these metallurgical processes. In an European Union (EU) research project "Minimization of dioxins in thermal industrial processes: mechanisms, monitoring and abatement (MINIDIP)", integrated iron and steel plant has been selected as one of the industrial sectors for further investigation. A large number of particulate samples (feed, belt siftings, electrofilter) were collected from the iron ore sintering installations from various steel plants and analyzed for their organochlorocompound contents. Measurable amounts of PCDD/F, PCBz, PCB were found for all samples. The various parameters influencing their de novo synthesis activity were also evaluated in laboratory experiments, and such activity was found to be moderate for samples from the ore sinter belt, but extremely high for some ESP dusts. Fine dust is active in a wide range of temperatures starting at 200 degrees C and declining above 450 degrees C; the optimal temperature for de novo synthesis was found to be around 350 degrees C; some inhibitors, such as triethanolamine, may reduce de novo activity by 50%, and lowering the O2 concentration in the gas stream leads to a much lower amount of PCDD/F formation. On the basis of their relative mass, typical operating conditions and specific activity of the different samples, the regions in the sintering plant where de novo synthesis may take place were tentatively established. PMID- 11219700 TI - PCDD/F inhibition by prior addition of urea to the solid fuel in laboratory experiments and results statistical evaluation. AB - The objectives of this work were to study the effect of urea addition to the fuel before the combustion on the suppression of PCDD/F emissions, to examine the influence of urea to PCDD/F isomer patterns by employing statistical analysis techniques and to determine the most effective method of urea addition. Urea in the form of powder and as an aqueous solution was mixed with RDF and the fuel mixtures were incinerated in a lab-scale reactor at 1000 degrees C. PCDD/F emitted during combustion experiments were collected in a quartz wool filter downstream the reactor unit. Analysis and quantification of PCDD/F showed that urea significantly affected PCDD/F emissions. Combustion of RDF containing 10% w/w urea resulted in PCDD/F emissions lower than 8 I-TEQ ng/g RDF, while the corresponding average value from single RDF combustion was 17 I-TEQ ng/g RDF. The PCDD/F prevention capacity of urea was independent from the method of urea addition to the fuel, as similar results were obtained after the addition of urea in the solid and in the aqueous phases. Results assessment by statistical methods showed that isomer patterns remained almost stable and were not affected by the method of urea addition. PMID- 11219701 TI - Hazardous air pollutant emissions from gas-fired combustion sources: emissions and the effects of design and fuel type. AB - Air emissions from gas-fired combustion devices such as boilers, process heaters, gas turbines and stationary reciprocating engines contain hazardous air pollutants (HAPs) subjected to consideration under the federal clean air act (CAA). This work presents a recently completed major research project to develop an understanding of HAP emissions from gas-fired boilers and process heaters and new HAP emission factors based on field emission tests of gas-fired external combustion devices used in the petroleum industry. The effect of combustion system design and operating parameters on HAP emissions determined by both field and research tests are discussed. Data from field tests of gas-fired petroleum industry boilers and heaters generally show very low emission levels of organic HAPs. A comparison of the emission data for boilers and process heaters, including units with and without various forms of NOx emission controls, showed no significant difference in organic HAP emission characteristics due to process or burner design. This conclusion is also supported by the results of research tests with different burner designs. Based on field tests of units fired with natural gas and various petroleum industry process gases and research tests in which gas composition was intentionally varied, organic HAP emissions were not determined to be significantly affected by the gas composition. Research data indicate that elevated organic HAP emission levels are found only under extreme operating conditions (starved air or high excess air combustion) associated with poor combustion. PMID- 11219702 TI - Research and development to improve naval shipboard waste management using a compact closed-loop-controlled waste incinerator. AB - Research has been conducted into the application of forced acoustics for enhancing the performance of a pyrolyzed waste afterburner configured as a dump combustor. Subscale studies showed that acoustic forcing of an air jet entering a dump chamber could trigger the formation of coherent vortices generated by entrainment of ambient gases. Subsequent studies showed that combustible gases could be introduced into the coherent vortices, and with additional modulation this configuration would lead to an enhanced combustion rate with low emissions of pollutants. The acoustically forced burner concept was scaled up to practical levels and tested as an afterburner on a commercial waste incinerator operating in pyrolysis mode. Results show that the afterburner can promote both compactness, due to the rapid combustion rate, and low pollutant emissions resulting from enhanced mixing prior to combustion. PMID- 11219703 TI - PAH and soot emissions from burning components of medical waste: examination/surgical gloves and cotton pads. AB - This is a laboratory investigation on the emissions from batch combustion of representative infectious ("red bag") medical waste components, such as medical examination latex gloves and sterile cotton pads. Plastics and cloth account for the majority of the red bag wastes by mass and, certainly, by volume. An electrically heated, horizontal muffle furnace was used for batch combustion of small quantities of shredded fuels (0.5-1.5 g) at a gas temperature of approximately 1000 degrees C. The residence time of the post-combustion gases in the furnace was approximately 1 s. At the exit of the furnace, the following emissions were measured: CO, CO2, NOx, particulates and polynuclear aromatic compounds (PACs). The first three gaseous emissions were measured with continuous gas analyzers. Soot and PAC emissions were simultaneously measured by passing the furnace effluent through a filter (to collect condensed-phase PACs) and a bed of XAD-4 adsorbent (to capture gaseous-phase PACs). Analysis involved soxhlet extraction, followed by gas chromatography-mass spectrometry (GC-MS). Results were contrasted with previously measured emissions from batch combustion of pulverized coal and tire-derived fuel (TDF) under similar conditions. Results showed that the particulate soot) and cumulative PAC emissions from batch combustion of latex gloves were more than an order of magnitude higher than those from cotton pads. The following values are indicative of the relative trends (but not necessarily absolute values) in emission yields: 26% of the mass of the latex was converted to soot, 11% of which was condensed PAC. Only 2% of the mass of cotton pads was converted to soot, and only 3% of the weight of that soot was condensed PAC. The PAC yields from latex were comparable to those from TDF. The PAC yields from cotton were higher than those from coal. A notable exception to this trend was that the three-ring gas-phase PAC yields from cotton were more significant than those from latex. Emission yields of CO and CO2 from batch combustion of cotton were, respectively, comparable and higher than those from latex, despite the fact that the carbon content of cotton was half that of latex. This is indicative of the more effective combustion of cotton. Nearly all of the mass of carbon of cotton gasified to CO and CO2 while only small fractions of the carbon in latex were converted to CO2 and CO (20% and 10%, respectively). Yields of NOx from batch combustions of latex and cotton accounted for 15% and 12%, respectively, of the mass of fuel nitrogen indicating that more fuel nitrogen was converted to NOx in the former case, possibly due to higher flame temperatures. No SO2 emissions were detected, indicating that during the fuel-rich combustion of latex, its sulfur content was converted to other compounds (such as H2S) or remained in the soot. PMID- 11219704 TI - Laboratory study on the high-temperature capture of HCl gas by dry-injection of calcium-based sorbents. AB - This is a laboratory study on the reduction of combustion-generated hydrochloric acid (HCl) emissions by in-furnace dry-injection of calcium-based sorbents. HCl is a hazardous gaseous pollutant emitted in significant quantities by municipal and hazardous waste incinerators, coal-fired power plants, and other industrial furnaces. Experiments were conducted in a laboratory furnace at gas temperatures of 600-1000 degrees C. HCl gas diluted with N2, and sorbent powders fluidized in a stream of air were introduced into the furnace concurrently. Chlorination of the sorbents occurred in the hot zone of the furnace at gas residence times approximately 1 s. The sorbents chosen for these experiments were calcium formate (CF), calcium magnesium acetate (CMA), calcium propionate (CP), calcium oxide (CX), and calcium carbonate (CC). Upon release of organic volatiles, sorbents calcine to CaO at approximately 700 degrees C, and react with the HCl according to the reaction CaO + 2HCl <=> CaCl2 + H2O. At the lowest temperature case examined herein, 600 degrees C, direct reaction of HCl with CaCO3 may also be expected. The effectiveness of the sorbents to capture HCl was interpreted using the "pore tree" mathematical model for heterogeneous diffusion reactions. Results show that the thin-walled, highly porous cenospheres formed from the pyrolysis and calcination of CF, CMA, and CP exhibited high relative calcium utilization at the upper temperatures of this study. Relative utilizations under these conditions reached 80%. The less costly low-porosity sorbents, calcium carbonate and calcium oxide also performed well. Calcium carbonate reached a relative utilization of 54% in the mid-temperature range, while the calcium oxide reached an 80% relative utilization at the lowest temperature examined. The data matched theoretical predictions of sorbent utilization using the mathematical model, with activation energy and pre-exponential factors for the calcination reaction of 17,000 K and 300,000 (g gas/cm2/s/atm gas), respectively. Thus, the kinetics of the calcination reaction were found to be much faster (approximately 500 times) than those of the sulfation reaction examined previously in this laboratory. PMID- 11219705 TI - Mechanistic studies on the role of PAHs and related compounds in PCDD/F formation on model fly ashes. AB - Model fly ashes containing Florisil, CuCl2.2H2O and PAHs with structures similar to dibenzo-p-dioxin or dibenzofuran were heated at 250 degrees C in He/O2 with regard to a supposed intramolecular reaction mechanism for oxygen incorporation. Highest reactivities in PCDF formation could be found for model compounds containing a biphenyl structure, while condensed pi-systems lead to a decrease in reactivity for such compounds. Biphenyl is almost completely converted to dibenzofuran. PCDD formation from six-membered rings like xanthene/9,10 dihydroanthracene is of minor importance. 18O-labeling of gaseous oxygen reveals no common reaction step for oxygen incorporation using 9-fluorenone, xanthene, diphenyl ether and diphenyl-2-carboxylic acid as model compounds. Pre-existing oxygen in reactants is a major source for ether groups in PCDD and PCDF. Determination of labeled and unlabeled CO and CO2 besides He/O2 reflects higher reactivities towards oxidation for model compounds containing ether groups than for compounds with carbonyl groups. PMID- 11219707 TI - Pressure effect on soot formation in turbulent diffusion flames. AB - Soot formation in a methane air turbulent jet diffusion flame is investigated numerically using a semi-empirical model. The temperature, density and species (the soot precursor C2H2) fields are calculated using detailed chemical kinetic mechanism based on the flamelet library approach. The influence of pressure on the soot formation and the behavior of the semi-empirical model in different flame situations are investigated. It is found that the flame shape and the flame temperature can be well predicted by the flamelet library approach. The calculated soot yield is mostly sensitive to the soot surface growth rate and the increase of pressure. The increase of pressure leads to the increase of soot surface growth rate and therefore to the increase of soot volume fraction. By adjusting a model constant in the soot surface growth rate, the soot emissions in both pressure p = 1 atm and p = 3 atm are properly simulated by the current semi empirical soot model. PMID- 11219706 TI - Adsorption of PCDD/F on MWI fly ash. AB - The removal of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) from waste incinerator off-gas is a costly task, because a considerable part of the PCDD/F may exist in the gas phase (often 50-100% around 200 degrees C). The volatile fraction passes the particle filter and the subsequent gas cleaning equipment, so that an additional unit is needed to remove the gaseous PCDD/F from the flue gas. Moreover, dioxins and furans can accumulate in some parts of the equipment in a way that they can act as a latent source. In this work, we investigate the possibility to adsorb the PCDD/F at the fly ash particles and to remove them during the filtration. The gas/particle partitioning of the PCDD/F depends on the temperature, the vapor pressure, the particle size, the particle number density and on the physical and chemical properties of the particle surface. These relationships are investigated by model calculations and by pilot scale experiments (500 Nm3/h) which employ one selected hexachlorinated dioxin congener. At room temperature, approx. 90% of the HxCDD are found in the particulate phase, while at 135 degrees C that portion is only 10%. This means that at ambient temperatures, the gas/particle partitioning of the dioxin corresponds well to the sublimation equilibrium. At higher temperatures, it is much different from the sublimation equilibrium and the apparent adsorption enthalpy is smaller than the enthalpy of sublimation. This observation is in agreement with literature data. From the above experiments and from similar literature data, the efficiency of fly ash particles as a sink for PCDD/F can be evaluated. The data suggest that the adsorption rate is not the limiting factor for the transfer into the particulate phase. The important factors appear to be the chemical composition of the fly ash and the temperature. PMID- 11219708 TI - Evidence for the contribution of methane in the formation of aromatics and soot in fuel-rich pre-mixed combustion. AB - Experimental results from an isothermal laminar flow reactor at atmospheric pressure are presented on the chemical composition in the post-oxidative region of two sooting fuel-rich pre-mixed mixtures diluted in nitrogen. A base case composed of n-heptane and O2 in N2 at 1425 K with a C/O of 2.85 was perturbed by substituting 10% of the carbon in n-heptane with carbon as CH4. While these changes would intuitively reduce aromatics and soot formation by increasing H2 and decreasing C2H2 concentrations, we observe the opposite. The concentrations of individual aromatic species are observed to actually increase by up to 50% and the soot yield increases by 80%. PMID- 11219709 TI - Analysis of exhausts emitted by i.c. engines and stationary burners, by means of u.v. extinction and fluorescence spectroscopy. AB - Optical investigations of the exhausts emitted by internal combustion (i.c.) engines and a stationary burner were performed, in order to assess their relative role as sources of organic matter to the atmosphere. Extinction spectra of air diluted exhausts in the 200-400 nm u.v. band reveal the expected existence of gaseous trace-species (NO, NO2 and SO2) and carbonaceous particulate matter (soot). In addition, after subtracting the absorption contribution from known species, a strong residual absorption band remains below 250 nm, which is attributed to organic aromatic matter, involving no more than two aromatic rings. A set of ex situ extinction and laser induced fluorescence (LIF) experiments were carried out on condensed combustion-water samples. Extinction measurements from the water samples show absorption spectra similar to those observed from air diluted samples, which are attributed to low volatility organic compounds, as they are trapped in the condensed phase. Combining the indications of extinction data for both air-diluted and condensed samples, it is suggested that the absorbing species might be molecular clusters of one/two aromatic rings. LIF spectra from condensed samples evidence two fluorescence bands, centered above 300 and 400 nm, respectively, whose intensities correlate with the combustion regimes. Analogous optical analysis on rain samples, collected in an urban area, showed that rain absorption and fluorescence spectra are similar to those found in condensed exhaust samples, which is consistent with the prevailing contribution of i.c. engines to the urban air pollution. The combined experimental data suggest that the absorbing and fluorescent species trapped in the condensed samples are organic (aromatic) compounds, involving mostly one two aromatic rings structural units, since they do not absorb above 250 nm. The overall molecular weight of the trapped material is likely heavy as they show low volatility. PMID- 11219710 TI - Fluorescence spectroscopy of aromatic species produced in rich premixed ethylene flames. AB - The fluorescence spectra of the condensed species (CS) collected in the soot inception region of a rich premixed laminar ethylene/oxygen flame have been measured by excitation in the UV at 266 and 355 nm excitation wavelength. The contribution of the most abundant polycyclic aromatic hydrocarbons (PAH) to the CS fluorescence has been evaluated in order to attribute the CS fluorescence at different emission wavelengths to specific aromatic structures. The fluorescence peaks detected in the UV region of the CS fluorescence spectrum was found to be mainly due to a typical PAH like fluorene, that is, the most fluorescent one among the PAH analyzed in the CS by chromatographic analysis. The CS exhibited the larger emission in the visible where the PAH contribution has been shown to be negligible and other fluorescing aromatic species, not identified by chromatographic analysis of the CS, have to be considered responsible for the visible fluorescence. Laser induced fluorescence (LIF) flame measurements excited at 266 nm and detected at two selected wavelengths (310 and 410 nm) have been performed along the flame axis and compared with the CS fluorescence intensity. The LIF and CS fluorescence signals show quite similar axial trends demonstrating that the LIF signals are related to CS fluorescence. In particular, the LIF fluorescence signals detected in the UV could be attributed to the PAH fluorescence whereas the unidentified species contained in the CS can be followed by LIF detection in the visible region. PMID- 11219712 TI - Characterization of emissions during the heating of tyre contaminated scrap. AB - In order to characterize the compounds (type and quantities) emitted during melting of organic contaminated scrap and to investigate the mechanism of their formation, an experimental set-up has been designed and built to study precisely the influence of temperature and gas atmosphere in the conditions of an electric arc furnace. These experiments lead to the determination of mass balances (C, H, O, S) and to the quantification of unburnt compounds (tars, carbon monoxide, volatile organic compounds (VOCs), benzene, toluene, ethylbenzene and xylenes (BTEX), polyaromatic compounds (PAHs)). Degradation conditions (gas atmosphere and temperature) corresponding to different areas in the electric furnace have also been investigated. Such experiments lead to a better understanding of degradation mechanisms; this interpretation is not possible from investigations performed in an industrial furnace since there are many uncontrolled parameters (large dispersion of the results). PMID- 11219711 TI - Identification of oxygenated compounds in combustion systems. AB - An attempt for the spectroscopic identification of oxygenated compounds produced in combustion processes under different environmental conditions is reported in this paper. A deeper knowledge about presence and evolution of such species in dependence of the operating conditions of practical burner represents a fundamental hint to the objective of an advancement of the control of combustion process and reduction of pollutant emissions. This paper mainly focuses on species characterized by the presence of carbonyl functionality since aldehydes, ketones and diketones are among the principal intermediate species and products of hydrocarbon oxidation. They are by themselves to be considered atmospheric pollutants and are also indicators of actual pathways followed during the chemical reactions occurring in the combustion process. For these reasons they are most suitable for the exploitation of the above indicated objectives. In this paper, a classification of spectroscopic features and markers of these classes of carbonyl compounds is presented on the basis of both literature and spectra collected from sample species. This interpretative scheme is then used for the attribution of fluorescence signals collected from a tetradecane spray in different environmental conditions. PMID- 11219713 TI - Evaluation of combustion by-products of MTBE as a component of reformulated gasoline. AB - Methyl tertiary-butyl ether (MTBE) is a gasoline oxygenate that is widely used throughout the US and Europe as an octane-booster and as a means of reducing automotive carbon monoxide (CO) emissions. The combustion by-products of pure MTBE have been evaluated in previous laboratory studies, but little attention has been paid to the combustion by-products of MTBE as a component of gasoline. MTBE is often used in reformulated gasoline (RFG), which has chemical and physical characteristics distinct from conventional gasoline. The formation of MTBE by products in RFG is not well-understood, especially under "worst-case" vehicle emission scenarios such as fuel-rich operations, cold-starts or malfunctioning emission control systems, conditions which have not been studied extensively. Engine-out automotive dynamometer studies have compared RFG with MTBE to non oxygenated RFG. Their findings suggest that adding MTBE to reformulated gasoline does not impact the high temperature flame chemistry in cylinder combustion processes. Comparison of tailpipe and exhaust emission studies indicate that reactions in the catalytic converter are quite effective in destroying most hydrocarbon MTBE by-product species. Since important reaction by-products are formed in the post-flame region, understanding changes in this region will contribute to the understanding of fuel-related changes in emissions. PMID- 11219714 TI - Ionically crosslinked alginate hydrogels as scaffolds for tissue engineering: part 1. Structure, gelation rate and mechanical properties. AB - Alginate gels have been used in both drug delivery and cell encapsulation applications in the bead form usually produced by dripping alginate solution into a CaCl2 bath. The major disadvantages to these systems are that the gelation rate is hard to control; the resulting structure is not uniform; and mechanically strong and complex-shaped 3-D structures are difficult to achieve. In this work controlled gelation rate was achieved with CaCO3-GDL and CaSO4-CaCO3-GDL systems, and homogeneous alginate gels were formulated as scaffolds with defined dimensions for tissue engineering applications. Gelation rate increased with increasing total calcium content, increasing proportion of CaSO4, increasing temperature and decreasing alginate concentration. Mechanical properties of the alginate gels were controlled by the compositional variables. Slower gelation systems generate more uniform and mechanically stronger gels than faster gelation systems. The compressive modulus and strength increased with alginate concentration, total calcium content, molecular weight and guluronic acid (G) content of the alginate. MC3T3-E1 osteoblastic cells were uniformly incorporated in the alginate gels and cultured in vitro. These results demonstrated how alginate gel and gel/cell systems could be formulated with controlled structure, gelation rate, and mechanical properties for tissue engineering and other biomedical applications. PMID- 11219715 TI - Effects of heparin immobilization on the surface characteristics of a biological tissue fixed with a naturally occurring crosslinking agent (genipin): an in vitro study. AB - Heparinized biomaterials have been used to manufacture blood-contacting prostheses. The present study was intended to characterize the surface properties of a genipin-fixed biological tissue immobilized with heparin using the methods of ionic binding (the /h-i tissue) or covalent binding via multi-point attachment (the /h-m tissue) or end-point attachment (the /h-e tissue). The surface characteristics of test tissues evaluated were water contact angle, surface tension, protein adsorption, platelet adhesion, and cellular compatibility. Nonheparinized and the glutaraldehyde-fixed counterparts were used as controls. It was found that immobilization of heparin on the glutaraldehyde- and genipin fixed tissues increased their hydrophilicity and surface tension and suppressed their mole ratio of adsorbed fibrinogen to adsorbed albumin and the amount of platelets adhered. Among the heparinized tissues, the /h-m tissue was more hydrophobic and had a higher mole ratio of adsorbed fibrinogen to adsorbed albumin and a greater amount of platelets adhered than the /h-i and /h-e tissues. In general, the surface characteristics of the /h-i tissue were comparable to the /h-e tissue. However, it is known that the ionically immobilized heparin may be displaced from the surface by an ion-exchange mechanism when exposed to blood. There were no significant differences in hydrophilicity, surface tension, the mole ratio of adsorbed fibrinogen to adsorbed albumin, and the amount of platelet adhesion between the glutaraldehyde- and genipin-fixed tissues in comparison with their respective counterparts. However, the cellular compatibility of the genipin fixed tissues with or without heparinization was significantly superior to its glutaraldehyde-fixed counterparts. PMID- 11219717 TI - Study of cell-material interaction by estimating NF-kappaB activation in HeLa S3 cells adhered onto hydrophilic substrates. AB - In order to interpret how cells recognize biomaterials, nucleic factor-kappa B (NF-kappaB) activation in the attached HeLa S3 cells on various substrates was evaluated. As substrates, materials of hydrophilic nature (cellulose, poly(acrylamide)-grafted poly(ethylene) (PAAm-g-PE), and lipids films) were used. The contemporary assay method for NF-kappaB was modified to fit our system. As a result, NF-kappaB activation varied depending on the substrates. The NF-kappaB outcome was induced significantly in the HeLa S3 cells that had adhered onto the lipid films in a short time. On the other hand, high levels of NF-kappaB induction were observed in the HeLa cells adhered to the celluose and PAAm-g-PE after a 24 h incubation period. The induction of NF-kappaB by cell-material interaction is discussed from the point of view of biocompatibility. PMID- 11219716 TI - Synthesis and characterization of N-isopropyl, N-methacryloxyethyl methacrylamide as a possible dental resin. AB - In this study, N-isopropyl, N-methacryloxyethyl methacrylamide (NIMM) is proposed as a possible reactive diluent in place of triethylene glycol dimethacrylate (TEGDMA) for dental resin mixtures. Real-time infrared spectroscopy was used to monitor the double-bond conversion as a function of irradiation time, and mixtures of 50/50wt% bis-GMA/NIMM were found to reach final conversions (95%) that were 1.5 times greater than bis-GMA/TEGDMA (65%) under visible light irradiation. In addition, samples cured to these conversions were tested with dynamic mechanical analysis. The bis-GMA/NIMM mixture (100% converted) was found to have a higher glass transition temperature and modulus at body temperature than a comparable bis-GMA/TEGDMA mixture (60% converted). Finally, the water sorption and solubility of bis-GMA/NIMM were determined to be higher than the bisGMA/TEGDMA comparison, but the values were still within the range of the ISO 9000s standard. These results suggest that bis-GMA/NIMM mixtures are a viable alternative to conventional dental resins since a greater degree of monomer conversion is obtainable without sacrificing physical and mechanical properties. PMID- 11219718 TI - Potassium ion release from a glass ionomer cement matrix. AB - Glass ionomer was mixed with water alone and with water containing two levels of potassium ion, added as potassium chloride. The dimensions of the specimens varied; discs, cylinders and a rectangular bar were used. Release of potassium was measured until it ceased. A little potassium was released from cement mixed with water but could be accounted for by traces present in the glass. Release took 2 months for the lower level and 1.5 years for the higher level of addition. For some specimen groups not all the potassium added was subsequently released. Potassium release tended towards the pattern found for fluoride release naturally occurring from glass ionomer cements in being proportional to t 1/2 but was less certain at the lower addition. Release was not related to the dimensions of the sample as has been shown for release of intrinsic fluoride. PMID- 11219719 TI - Bone reactions to nacre injected percutaneously into the vertebrae of sheep. AB - We have studied the osteogenic effects of nacre (mother of pearl) placed in experimental cavities prepared in the lumbar vertebrae of sheep. Some of cavities were filled with nacre, some with PMMA, and some were left empty. The vertebrae were removed 1, 8, 12 weeks after surgery, and assessed histologically and morphometrically. The nacre particles in the bone cavity and the surrounding intertrabecular spaces gradually dissolved beginning at 8 weeks after surgery. There were layers of newly formed bone, both woven and lamellar, in various stages of maturation in contact with or adjacent to the dissolving nacre. Quantitative assessment of the activation of bone formation adjacent to the cavities filled with nacre indicated significant activation of bone formation, which continued until week 12. There was also increased mineralization of the host bone at this time. There was no new bone formation in the empty cavities, or in those filled with PMMA. PMMA also caused necrosis of surrounding bone cells with a change in bone architecture and significant reductions in bone formation and mineralization. This study demonstrates that nacre stimulates bone-forming cells in vertebrae and appears to result in new bone formation. PMID- 11219720 TI - In vivo-in vitro study of biodegradable methadone delivery systems. AB - Three one-week controlled-release methadone formulations: polylactic acid microspheres (F-PLA) and poly(lactide-co-glycolide) microspheres (F-PLGA) with 24 and 30% methadone content, respectively, and an implant of 50:50 poly(lactide-co glycolide): methadone, were evaluated in vitro and in vivo. The implant released the total amount of methadone in vitro while microsphere formulations released the methadone incompletely, 63% from F-PLA and 85% from F-PLGA in a week. Methadone release in vivo was estimated by deconvolution, F-PLGA giving a bioavailability >99% (methadone was totally released in 48h), while the estimated bioavailability of F-PLA was lower than expected. The bioavailability of the implant by deconvolution was around 60%, but absence of methadone in the implant indicated its complete release. These differences are due to an increase in methadone clearance after 72 h of the in vivo experimental period had passed, disturbing a good in vivo-in vitro correlation. A linear correlation between in vitro methadone release and in vivo release calculated from the amount of drug remaining within the implant, was found until the drug was completely released. PMID- 11219721 TI - A study of HAp/PLLA composite as a substitute for bone powder, using FT-IR spectroscopy. AB - Chemically synthesized hydroxyapatite/poly-L-lactide (HAp/PLLA) composite biomaterial was studied in vivo. The biocomposite was implanted into Balb/c Singen mice and after 1 and 3 weeks removed from their organisms and analyzed by the FT-IR spectroscopy. After 1 week of testing in vivo the implanted sample gave a spectrum in which absorption bands arising from newly formed functional groups of amine and peptide can be seen. After 3 weeks, a spectrum with pronounced absorption bands at 3420 and 1650cm(-1) assigned to newly generated collagen, a component of the extracellular connective-tissue matrix, was registered. Also, decrease of the intensity absorption band at 1760cm(-1) originating from the C=O group of PLLA indicates bioresorption of the PLLA used. Analysis of the microstructure of the sample surface by scanning electron microscopy before and after implantation revealed bioresorption of the PLLA polymer phase and generation of collagen fibers at the sites of implanted bioresorptive PLLA. A mixture of autologous bone powder and HAp/PLLA biocomposite was also examined. After implantation, the same final products as in the case of HAp/PLLA composite biomaterial used alone were found. PMID- 11219722 TI - Calcium phosphate invert glass-ceramic coatings joined by self-development of compositionally gradient layers on a titanium alloy. AB - A glass-ceramic layer containing beta-Ca3(PO4)2 crystals could be joined easily with a new type of titanium alloy (Ti-29Nb-13Ta-4.6Zr) consisting of a beta titanium phase by heating the metal, on which glass powders with a composition of 60CaO x 30P2O5 7Na2O x 3TiO2 were placed, at 800 degrees C in air. Measurement of tensile bonding strength revealed that the joining between the coating layer and the substrate is very strong. Even after the large deformation (e.g., approximately 90 degrees in bending angle) of the titanium alloy, the coating layer was not peeled off from the substrate. A compositionally gradient layer in the TiO2-P2O5-Na2O-CaO system is developed automatically on the titanium alloy during the heating, resulting in the formation of the strong joining. By soaking in simulated body fluid at 37 degrees C, hydroxyapatite phase was formed newly on the surface of the coating layer. PMID- 11219723 TI - Fabrication of hydroxyapatite bodies by uniaxial pressing from a precipitated powder. AB - Hydroxyapatite (OHAp) has been obtained by using a precipitation method. Thermal stability of the precipitated powder has been checked to define an appropriate working range to process ceramic bodies without the appearance of odd phases. Pellets of hydroxyapatite have been manufactured by means of uniaxial pressing and convenient thermal treatments have been investigated to achieve high density OHAp bodies. Finally, factors that could affect the ultimate mechanical properties of the sintered bodies prepared by uniaxial pressing have been discussed. PMID- 11219724 TI - Influence of sol and stage of spinnability on in vitro bioactivity and dissolution of sol-gel-derived SiO2 fibers. AB - The ability of the sol-gel-derived green state silica fibers to induce the formation of bone-like calcium phosphate (HCA) on their surfaces has not been studied earlier. Bioactive silica fibers provide alternatives for the design of novel products, e.g., as implants used in tissue guiding or bone repairs. In this study, dry spinning was used to prepare the sol-gel fibers. Different fibers with different bulk structures were prepared by changing the composition and controlling the stage of spinnability. Additionally, the influence of the aging time of the fibers on the bulk structure of the samples was investigated. Furthermore, the ability to form calcium phosphate was investigated in vitro in the simulated body fluid (SBF). Transmission electron microscopy was used to illustrate the bulk structure of the green state fibers and scanning electron microscopy to illustrate the formed calcium phosphate layer on the fibers. The fibers were additionally characterized by measuring the dissolution of the silica in the SBF. In vitro bioactive silica fibers were successfully prepared. The calcium phosphate layer was formed within 1-5 days in the best case. The structural stability and the in vitro bioactivity varied with the aging time expect in one case where practically stable fibers could be prepared. The concentration of silica released in the SBF had no direct connection with the HCA formation. The silica-rich gel layer was not observed on the fibers, but the structure of the fibers was suggested to have an important role in the HCA formation. PMID- 11219725 TI - Surface analysis of Ti-15Zr-4Nb-4Ta alloy after implantation in rat tibia. AB - A new Ti-15Zr-4Nb4Ta alloy without V was implanted in rat tibiae for 6-48 weeks. The new bone formation surrounding the Ti implant in bone marrow, surface analysis of the Ti alloy after implantation, and metal concentrations in dried bone tissue containing new bone were investigated. New bone was well formed around the Ti-15Zr-4Nb-4Ta alloy implanted in bone marrow. The mean thickness of the new bone increased up to 24 weeks after implantation, and changes in the mean thickness thereafter, up to 48 weeks. were very small. The number of corrosion pits observed in the Ti-6Al-4V extra low interstitial (ELI) alloy surface tended to be slightly more than that of the Ti-5Zr-4Nb-4Ta alloy implant. The concentrations of metal elements in the bone tissue containing the new bone tended to increase slightly more than in bones without the implant. PMID- 11219727 TI - The effects of scaffold thickness on tissue engineered cartilage in photocrosslinked poly(ethylene oxide) hydrogels. AB - The thickness of human articular cartilage has been reported to vary from less than 0.5 up to 7 mm. Hence, tissue engineered cartilage scaffolds should be able to span the thickness of native cartilage to fill defects of all shapes and sizes. In this study, we demonstrate the potential for using photopolymerization technology to encapsulate chondrocytes in poly(ethylene oxide) hydrogels, which vary in thickness from 2 to 8 mm. Chondrocytes, encapsulated in an 8 mm thick, photocrosslinked hydrogel and cultured in vitro for 6 weeks, remained viable and produced cartilaginous tissue throughout the construct comparable to a 2 mm thick gel as seen both histologically and biochemically. In addition, the total collagen and glycosaminoglycan contents per wet weight of the 8 mm thick cell polymer construct were 0.13 +/- 0.01 and 0.25 +/- 0.03%, respectively, and did not vary significantly as a function of spatial position in the construct. The histological evidence and the biochemical content were similar in all constructs of varying thickness. The results suggest that photocrosslinked hydrogels are promising scaffolds for tissue engineering cartilage as cell viability is readily maintained; uniform cell seeding is easy to achieve: and the biochemical content of the extracellular matrix is not compromised as the scaffold thickness is increased from 2 to 8 mm. PMID- 11219726 TI - Thermal compression and characterization of three-dimensional nonwoven PET matrices as tissue engineering scaffolds. AB - Nonwoven fibrous matrices have been widely used as scaffolds in tissue engineering, and modification of microstructure of these matrices is needed to organize cells in three-dimensional space with spatially balanced proliferation and differentiation required for functional tissue development. The method of thermal compression of nonwoven polyethylene terephthalate (PET) fabrics was developed and key parameters of temperature, pressure, and compression duration were evaluated in this study. The permanent deformation was obtained at elevated temperature under pressure and the viscoelastic compressional behaviors were observed, characterized by a distinct apparent modulus change in glass transition temperature region. A liquid extrusion method was further employed to analyze both pore size and its distribution for matrices with porosity ranging from 84 to 93%. It is also found that a more uniformly distributed pore size was resulted from thermal compression and the isotropic nature of nonwoven fabrics was preserved because of the proportional reduction of the pore by compression. The thermally compressed fabric matrices with two different pore sizes (15 and 20 microm in pore radius) were used to culture human trophoblast ED27 and NIH 3T3 cells. It was found that cells cultured in the different pore-size PET matrices had different cell spatial organization and proliferation rates. The smaller pores in the matrix allowed cells to spread better and proliferate faster, while cells in the larger pores tended to form large aggregates and had lower proliferation rate. The thermal compression technique also can be applied to other synthetic fibrous matrices including biodegradable polymers used in tissue engineering to modify the microstructure according to their viscoelastic properties. PMID- 11219728 TI - Lysis of Gymnodinium breve by cultures of the green alga Nannochloris eucaryotum. AB - Laboratory cultures of Florida's red tide organism, Gymnodinium breve, were killed by the green alga Nannochloris eucaryotum. Studies involved organism organism interaction as well as organism-cell-free culture (N. eucaryotum) interaction. Both studies demonstrated that N. eucaryotum adversely affected Florida's red tide organism. The lysis has been attributed to compounds called APONINs (apparent oceanic naturally occurring cytolins). N. eucaryotum crude APONIN was extracted from cell-free cultures, partially purified and fractionated. The fractions were bioassayed against G. breve, and 'fingerprints' of the deleterious fractions were obtained. PMID- 11219729 TI - A strategy for the identification of T-cell epitopes on Leishmania cysteine proteinases. AB - In this study computational analysis was used to compile sequence alignments, construct a dendrogram and calculate physical data in order to predict potential T-cell epitopes of the Leishmania cysteine proteinase. Using multiple alignment of human and Leishmania proteinase sequences deposited on data bank sequences, it was possible to predict that the extreme C-terminus of cysteine proteinase (Cyspep, 355-444) contained three peptides (pI 361-370, pII 415-422 and pIII 431 444) with charge score, hydrophobicity and isoelectric points compatible for human leucocyte-associated antigen (HLA) class II binding. The prediction was confirmed in vitro through the ability of synthetic peptides corresponding to the predicted regions to stimulate peripheral blood mononuclear cells of patients with leishmaniasis. PMID- 11219730 TI - Altered expression of keratins during abnormal wound healing in human skin. AB - Keloids and hypertrophic scars are a result of aberrations of the normal wound healing processes of the skin. The expression of keratins, the proteins of an intermediate filament supergene family, closely parallel the division/differentiation of epithelial cells and therefore offer excellent molecular markers to examine wound healing. In this study, the expression of K5/K14, proliferation specific keratin polypeptides in normal skin, keloids and hypertrophic scars was analysed. Results indicated that unlike normal wounds and hypertrophic scars, keloid epidermis displayed increased expression of K5 and K14 at both the translational and transcriptional levels. The molecular mechanisms in the pathogenesis of keloids appear to be different from those of hypertrophic scars. PMID- 11219731 TI - Recovery of gravitropic response during regeneration of root caps does not require developed columella cells and sedimentation of amyloplasts. AB - Correlations between regeneration of the root cap and recovery of a gravitropic response were studied using primary roots of Phaseolus vulgaris. After removal of various lengths of the root tip a gravistimulus was continuously given to the root. The statistical analysis of data showed that recovery of the gravitropic response was gradually delayed as the length of the tips removed increased. This suggested that the columella cells of the root cap were involved in gravitropism. When the root cap was completely removed, the roots did not respond to gravistimuli for the first 15 h and began to reorient their growth direction at 20 h. At this time, the columella cells had just begun to regenerate and had immature amyloplasts which did not sufficiently form a sediment. These results suggest that other systems of perception exist in plant cells in addition to the amyloplast-based model of graviperception. PMID- 11219732 TI - Sex bodies and synaptonemal complexes of Balb/C mice: antioxidant intervention of oxyradical insult. AB - Spermatogenesis is inhibited in Balb/C mice as a result of oxyradical insult. However, mammalian spermatocytes and synaptonemal complexes retain their structure and function after oxyradical insult due to protection afforded by the antioxidant vitamin E. Control groups were compared with experimental groups which were fed various vitamin E-deficient diets and subjected to varying times in an humidified 100% oxygen (hyperoxia) chamber. Measurements were made of sex body volume (SBV), nuclear envelope aberrations (NEA), and synaptonemal complex structure in spermatocytes during pachytene of meiosis prophase I. Changes in the volume of the sex body were positively correlated with increased oxyradical insult. The structure of the synaptonemal complex was not altered in any of the experimental groups which is a significant observation. It is suggested that vitamin E affords antioxidant protection and inhibits the alteration of membranes and sex chromosomes in mice during meiosis. PMID- 11219733 TI - Glucose sensor with improved haemocompatibilty. AB - A new biocompatible copolymer has been synthesised and used in an electrochemical enzyme-based glucose sensor. The copolymer incorporates three segments including a monomer with an electrically neutral phosphorylcholine head group that is able to reject protein adsorption and two segments that increase the affinity to polyurethane substrate. Peel and solution circulation tests showed that this material has high attachment to polyurethane. With the new copolymer as the outermost layer and the polyurethane as the diffusion-limiting membrane, the sensor showed extended linearity up to 50 mM glucose and stable output in bovine serum for 70 h. During in vivo tests, the sensor exhibited a steady current signal and a rapid transient response when the glucose concentration was raised. These results imply that the haemocompatibility of the glucose sensor coated with the new copolymer has been improved, which is crucial for a sensor used for clinical real-time monitoring. The material may also be suitable for application to other implantable devices. PMID- 11219734 TI - Parameters important in tuning the response of monolayer enzyme electrodes fabricated using self-assembled monolayers of alkanethiols. AB - Enzyme electrodes were observed experimentally to have a broad dynamic range, high sensitivity and excellent reproducibility. The theoretically predicted response of the monolayer enzyme electrodes was in good agreement with that observed experimentally over the broad range of experimental conditions tested. The response is limited by the rate of enzyme turnover by a mediating species rather than mass transport. As a consequence of this limitation, the response was very sensitive to the enzyme loading and the concentration of mediator in the sample solution but insensitive to mass transport variables such as solution stirring or the diffusion coefficients of the substrate or cosubstrate. PMID- 11219735 TI - Quantification of nisin in flow-injection immunoassay systems. AB - A monoclonal-antibody-based, sequential competitive-flow-injection immunoassay system in expanded-bed mode has been developed for the determination of nisin. The system allows the determination of nisin in the presence of suspended particles without any significant interference, illustrating its potential for on line monitoring of fermentation processes or the analysis of food matrices. The dose response range of the system when operated in expanded-bed mode was 6-90 microM. The detection limit under packed-bed conditions was 3 microM. The results correlated well with the results from conventional ELISA in the analysis of samples of processed cheese. When milk samples, fermentation samples and buffer were spiked with nisin, the mean recoveries were 86% for milk samples, 96% for fermentation samples and 98% for buffer solution. PMID- 11219736 TI - Diagnosis of diabetes by image detection of breath using gas-sensitive LAPS. AB - Gaseous respiratory acetone detection using LAPS (Light Addressable Potentiometric Sensors) is proposed as a supplementary method for the diagnosis of diabetes. First, electric simulation of the LAPS system is studied to obtain the optimum sensitivity of tested odours. Gas phase chromatography is used to obtain correlations between blood sugar levels and acetone from the breath. Then several experiments are carried out to obtain the 2-dimension static and dynamic images of respiratory acetone and air. All experimental results show that the LAPS can be very useful for the detection of respiratory odours, especially the diagnosis of diabetes. PMID- 11219737 TI - Development of a disposable ethanol biosensor based on a chemically modified screen-printed electrode coated with alcohol oxidase for the analysis of beer. AB - A disposable amperometric biosensor for the measurement of ethanol has been developed. It comprises a screen-printed carbon electrode doped with 5% cobalt phthalocyanine (CoPC-SPCE), and coated with alcohol oxidase; a permselective membrane on the surface acts as a barrier to interferents. The measurement of ethanol is based on the signal produced by H2O2, the product of the enzymatic reaction. Optimisation studies were performed using amperometry in stirred solution and the magnitude of the signal was found to be dependent on pH, enzyme loading, type of membrane and applied potential. The same technique was used to evaluate the biosensor for the determination of ethanol in samples. The results obtained compared well with the manufacturers specifications. In order to test the possibility of using the devices in the field, chronoamperometry was also used to determine ethanol in the same beer samples. The precision and recovery data again indicated that the biosensor should give reliable results under the conditions described. PMID- 11219738 TI - Screen-printed amperometric microcell for proline iminopeptidase enzyme activity assay. AB - A microfabricated amperometric microcell was designed and used for the determination of proline iminopeptidase (PIP) enzyme activity in 2-10-microl samples. The measurements were made in the range of 10.3-841.5 mU/ml enzyme activities. The sensitivity of the determinations was between - 0.0195 and - 0.0203 microA ml/mU per min. The coefficient of variation of the determined values ranged between 2.8 (at 561.2 mU/ml) and 24.1% (at 10.3 mU/ml). The microcell was manufactured on an alumina substrate using screen-printed graphite working and Ag/AgCl reference electrodes. Elevated PIP activity in the vaginal fluid is a biochemical indicator of bacterial vaginosis. The method is appropriate to differentiate between normal (66+/-145 mU/ml) and elevated, diseased (704+/-145 mU/ml), values. PMID- 11219739 TI - Materials and techniques for electrochemical biosensor design and construction. AB - New developments in biosensor design are appearing at a high rate as these devices play increasingly important roles in daily life. This review aims to highlight recent developments in materials and techniques for electrochemical biosensor design and construction. Rapid growth in biomaterials, especially the availability and application of a vast range of polymers and copolymers associated with new sensing techniques have led to remarkable innovation in the design and construction of biosensors, significant improvements in sensor function and the emergence of new types of biosensor. Nevertheless, in vivo applications remain limited by functional deterioration due to surface fouling by biological components. However, new copolymers based upon biomembrane mimicry have been extensively investigated during the last two decades, raising hopes that the problems related to interactions between foreign surfaces and biological fluids and tissues may soon be solved. PMID- 11219740 TI - High sensitivity waveguide grating sensor based on radiative losses. AB - A scheme of a waveguide sensor utilizing an output grating coupler with the grating length less than the coupling length is analyzed. This is the new method for the evaluation of average thickness of the adsorbed layer. This method, based on measurements of radiation loss coefficients, is proposed. Sensitivity limits of such a scheme are discussed. The new scheme has strong response on formation on the adsorbed layer and relatively weaker response on the fluctuations of temperature and analyte concentration. New possibilities for multiparameter sensing are shown. PMID- 11219741 TI - Electrochemical genosensor design: immobilisation of oligonucleotides onto transducer surfaces and detection methods. AB - The present report reviews immobilisation techniques of purified oligonucleotides on electrochemical transducers and their corresponding detection techniques. Most of the literature reviewed was published in the 1990s. The immobilisation techniques of a DNA probe to the surface of an electrochemical transducer made from carbon, gold, platinum or polypyrrole, ranged from simple adsorption to covalent bonding. Recent efforts to couple the recognition layer containing the immobilised nucleic acid recognition layer with the electrochemical signal transducer are discussed. Special attention is given to hybridisation biosensing based on electroactive indicators. PMID- 11219742 TI - Detection of protease activity in the wetted surface of gelatin-coated electrodes in air by AC impedance spectroscopy. AB - As a step towards developing a biosensor which can detect airborne protease droplets, a biosensor which had previously been developed to detect protease in solution is shown to be capable of detecting different concentrations of protease in liquid films on the sensor surface in air. The biosensor measured impedance change due to proteolytic digestion of its gelatin coating. In saturated air there was a rise in impedance, with a loss in weight of the gelatin, in proportion to collagenase concentration. The addition of glycerol to the gelatin caused a lower impedance response and smaller loss in weight. A critical thickness of the gelatin layer prior to a more rapid change in the rate of impedance was noted, with and without the addition of glycerol. In low air humidity (40%), with gelatin, all collagenase concentrations produced a very similar rapid increase in impedance. However, with glycerol-enhanced gelatin, there was a clear distinction between the extent of impedance change with different collagenase concentrations. The application of these findings for use in the field of bioaerosol sampling is discussed. PMID- 11219743 TI - Colloidal gold as an electrochemical label of streptavidin-biotin interaction. AB - A new electrochemical method to monitor biotin-streptavidin interaction, based on the use of colloidal gold as an electrochemical label, is investigated. Biotinylated albumin is adsorbed on the pretreated surface of a carbon paste electrode (CPE). This modified electrode is immersed in colloidal gold streptavidin labelled solutions. Adsorptive voltammetry is used to monitor colloidal gold bound to streptavidin, obtaining a good reproducibility of the analytical signal (R.S.D. = 3.3%). A linear relationship between peak current and streptavidin concentration from 2.5 x 10(-9) to 2.5 x 10(-5) M is obtained when a sequential competitive assay between streptavidin and colloidal gold-labelled streptavidin is carried out. On the other hand, the adsorption of streptavidin on the electrode surface was performed, followed by the reaction with biotinylated albumin labelled with colloidal gold. In this way, a linear relationship between peak current and colloidal gold labelled biotinylated albumin concentration is achieved with a limit of detection of 7.3 x 10(9) gold particles per ml (5.29 x 10(-9) M in biotin). PMID- 11219745 TI - Current awareness in biosensors & bioelectronics. PMID- 11219744 TI - A micro flow injection electrochemical biosensor for organophosphorus pesticides. AB - We describe a disposable, amperometric micro flow injection electrochemical biosensor that can be applied to the identification and quantification of highly toxic organophosphorus (OP) compounds in the environment, on the spot and in a short time. The system traces very small quantities of OP by monitoring the enzymatic reaction of acetylcholine esterase (AChE) and its inhibition. The sensor is sensitive, rapid, small, inexpensive, disposable and can be operated by non-professional technicians. The electrochemical cell consists of screen-printed electrodes covered with an enzymatic membrane and placed in a home-made flow cell. The electrodes are connected to a computer-controlled potentiostat. We quantitatively detected the OP compound, dimethyl 2,2-dichlorovinyl phosphate (DDVP), by monitoring the OP induced decrease in enzymatic degradation of the substrate, acetylthiocholine chloride (ATCh), to thiocholine and acetic acid. Thiocholine reacts with hexacyanoferrate ion in the working solution and the reduction of [Fe(CN)6](-3) to [Fe(CN)6](-4) and its subsequent reoxidization by the electrode generates very sharp, rapid and reproducible electric signals. The ability to detect low quantities is extremely important when dealing with hazardous environmental pollutants. PMID- 11219746 TI - An intelligent rapid odour recognition model in discrimination of Helicobacter pylori and other gastroesophageal isolates in vitro. AB - Two series of experiments are reported which result in the discrimination between Helicobacter pylori and other bacterial gastroesophageal isolates using a newly developed odour generating system, an electronic nose and a hybrid intelligent odour recognition system. In the first series of experiments, after 5 h of growth (37 degrees C), 53 volatile 'sniffs' were collected over the headspace of complex broth cultures of the following clinical isolates: Staphylococcus aureus, Klebsiella sp., H. pylori, Enterococcus faecalis (10(7) ml(-1)), Mixed infection (Proteus mirabilis, Escherichia coli, and E. faecalis 3 x 10(6) ml each) and sterile cultures. Fifty-six normalised variables were extracted from 14 conductive polymer sensor responses and analysed by a 3-layer back propagation neural network (NN). The NN prediction rate achieved was 98% and the test data (37.7% of all data) was recognised correctly. Successful clustering of bacterial classes was also achieved by discriminant analysis (DA) of a normalised subset of sensor data. Cross-validation identified correctly seven 'unknown' samples. In the second series of experiments after 150 min of microaerobic growth at 37 degrees C, 24 volatile samples were collected over the headspace of H. pylori cultures in enriched (HPP) and normal (HP) media and 11 samples over sterile (N) cultures. Forty-eight sensor parameters were extracted from 12 sensor responses and analysed by a 3-layer NN previously optimised by a genetic algorithm (GA). GA NN analysis achieved a 94% prediction rate of 'unknown' data. Additionally the 'genetically' selected 16 input neurones were used to perform DA-cross validation that showed a clear clustering of three groups and reclassified correctly nine 'sniffs'. It is concluded that the most important factors that govern the performance of an intelligent bacterial odour detection system are: (a) an odour generation mechanism, (b) a rapid odour delivery system similar to the mammalian olfactory system, (c) a gas sensor array of high reproducibility and (d) a hybrid intelligent model (expert system) which will enable the parallel use of GA-NNs and multivariate techniques. PMID- 11219747 TI - Designing an amperometric thick-film microbial BOD sensor. AB - Thick film oxygen electrodes manufactured by screen print method have been used as a transducer for a biochemical oxygen demand (BOD) sensor. The kinetics of the immobilized yeast, Arxula adeninivorans (Arxula) has been studied. The apparent KM of immobilized Arxula (> 100 microM) is higher than free cells of Arxula (70 microM). The increase in KM caused by the effect of immobilization extends the linear range of the sensor. End-point measurement and quasi-kinetic measurement have been studied comparatively as measurement procedures with a good correlation. The Vmax for end-point measurement is 790.7 microM/s and that for quasi-kinetic measurement is 537.3 microM/s. The limit of detection is calculated 1.24 mg/l BOD. Using the quasi-kinetic measurement, instead of end-point measurements, the measuring time can be reduced from 5-30 min to 100 s. The sensor layer thickness or increase in the layer of covering gel can increase the KM that is accompanied with the extension of the linear range of the sensor. Nevertheless, increase in the layer of covering gel will not increase the saturation signal. Domestic wastewater was checked by the thick film BOD sensor and the results are satisfactory. PMID- 11219748 TI - Effect of incident angle of light on sensitivity and detection limit for layers of antibody with surface plasmon resonance spectroscopy. AB - The effect of the incident angle of light on sensitivity and the detection limit for surface-plasmon resonance spectroscopy were examined. The sensitivities and the detection limit were experimentally measured using an antibody as a modeled analyte in the incident angles of a light region of 66-76 degrees. The results showed that the sensitivity of a smaller incident angle was higher than that of a larger one. For instance, the sensitivity of a 66 degree incident angle was three times higher than that of a 76 degree incident angle. The detection limit with a 66 degree incident angle was one-tenth of that with a 76 degree incident angle. These sensitivities and detection limits were compared with those of a commercially produced surface-plasmon resonance instrument. This comparison demonstrated that a wavelength resolution of the order of less than 10(-2) nm was necessary to obtain satisfactory sensitivities and detection limits. In addition, the refractive index and thickness of the antibody layer formed on a sensor surface was proposed by experimental results and theoretical calculation. PMID- 11219749 TI - Coupling of a DNA piezoelectric biosensor and polymerase chain reaction to detect apolipoprotein E polymorphisms. AB - In this paper we report the coupling of the Polymerase Chain Reaction (PCR) with a piezoelectric biosensor to detect a point mutation in a human gene. Biotinylated 23-mer probes were immobilised on the streptavidin coated gold surface of a quartz crystal; streptavidin was covalently bound to the thiol/dextran modified gold surface. The hybridisation of the immobilised probes with a short sequence (23 mer) complementary, non-complementary and mismatched DNA was investigated: the device was able to distinguish the different synthetic oligonucleotides. Many cycles of measurements can be performed on the same crystal surface regenerating the single strand of DNA with 1 mM of HCl. The same hybridisation reaction was then performed using real samples of human DNA extracted from blood and amplified by PCR, following a standard procedure for genetic detection of the polymorphism of the apolipoprotein E (apoE) gene. The procedure was able to distinguish the sequences present in the different samples, which differ only in one base: in this way it was possible distinguish between different groups of genotypes with apoE typing. Experiments with 'blank' samples confirmed the absence of adsorption or non-specific effects on the quartz crystal treated with the reported procedure. PMID- 11219750 TI - Optical fiber biosensor for the determination of low biochemical oxygen demand. AB - An optical fiber biosensor was developed for the evaluation of low Biochemical Oxygen Demand (BOD) values in river waters. Artificial wastewater (AWW) solution was employed as standards for the calibration of the BOD sensor. The response time of the sensor was 15 min, and the optimal BOD response was observed at 30 degrees C, pH 7.0. A linear relationship was obtained between the output voltage and BOD5 values, and the range of determination was 1-10 mg l(-1) BOD. The sensor response was almost not influenced by chloride ion up to 1000 mg l(-1), and also not affected by heavy metal ions (Fe3+, Cu2+, Mn2+, Cr3+, Zn2+). The BOD of river waters was estimated by using the optical fiber biosensor, and good correlation between the sensor and BOD5 test was obtained (r2 = 0.971). PMID- 11219751 TI - Enzyme kinetic assays with surface plasmon resonance (BIAcore) based on competition between enzyme and creatinine antibody. AB - A procedure is described which allows the characterization of enzyme by a hybrid approach using an enzyme and an antibody. The presented method is related to the affinity determination of antibodies by the 'affinity in solution' procedure for BlAcore. The antibody is used as an indicator for the concentration of substrate, which is also the antigen. A mixture of enzyme, substrate and antibody is incubated, and an aliquot of this solution is injected periodically into a flowcell containing immobilized substrate, which is bound by the antibody, but not cleaved by the enzyme. The chosen initial concentration of substrate inhibits the binding of antibody to the immobilized substrate by 90%. During the enzymatic reaction, increased amounts of antibody bind to the surface, as the substrate concentration is decreased. With this method, the cleavage of creatinine with creatinine iminohydrolase (6 mU/ml) was monitored for up to 11 h. A recently developed monoclonal antibody against creatinine was used as the indicating protein. For the calculation of enzyme activity, the signals were compared with a calibration curve for inhibition of antibody binding to the chip by creatinine in solution. PMID- 11219752 TI - Drug evaluations using neuronal networks cultured on microelectrode arrays. AB - We used spontaneously active neuronal networks derived from dissociated embryonic murine spinal cord and auditory cortex and grown on substrate-integrated thin film microelectrodes to determine characteristic responses to the cannabinoid agonists anandamide (AN) and methanandamide (MA). AN and MA reversibly inhibited spike and burst production in both tissue types. Responses of 21 cultures ranging in age from 23 to 111 days in vitro (d.i.v.) showed high intra- and inter-culture reproducibility at all ages. However, responses were tissue and substance dependent. AN and MA were equipotent in cortical cultures and terminated bursting and spiking at 2.5 +/- 0.9 microM (n = 10). Spinal cultures were shut-off by 1.3 +/- 0.7 microM (n = 15) AN, but required 5.8 +/- 1.2 microM MA for activity cessation. MA, but not AN, demonstrated a biphasic influence: excitation at 0.25 3.5 microM and suppression at 4-7.1 microM. Palmitoylethanolamide, a related lipophilic molecule with no reported binding to the CBI receptor (to which AN and MA bind in the central nervous system), did not affect network activity at concentrations up to 6.5 microM. Irreversible cessation of activity was observed after 30 min applications of AN or MA at > 7 microM. PMID- 11219753 TI - Silica sol-gel composite film as an encapsulation matrix for the construction of an amperometric tyrosinase-based biosensor. AB - An amperometric tyrosinase enzyme electrode for the determination of phenols was developed by a simple and effective immobilization method using sol-gel techniques. A grafting copolymer was introduced into sol-gel solution and the composition of the resultant organic-inorganic composite material was optimized, the tyrosinase retained its activity in the sol-gel thin film and its response to several phenol compounds was determined at 0 mV vs. Ag/AgCl (sat. KCl). The dependences of the current response on pH, oxygen level and temperature were studied, and the stability of the biosensor was also evaluated. The sensitivity of the biosensor for catechol, phenol and p-cresol was 59.6, 23.1 and 39.4 microA/mM, respectively. The enzyme electrode maintained 73% of its original activity after intermittent use for three weeks when storing in a dry state at 4 degrees C. PMID- 11219754 TI - Increasing the sensitivity of piezoelectric odour sensors based on molecularly imprinted polymers. AB - The molecular imprinting technique has been used to create sensors with a predetermined selectivity for molecules in the gas phase. Based on previous results, piezoelectric quartz crystals were first coated with a layer of nylon, to provide increased sensitivity, and then a layer of a polymer imprinted with 2 methylisoborneol (MIB) was applied to endow the device with selectivity. The response of the 'imprinted' sensor was significantly higher than the response of the 'non-imprinted' sensor at MIB concentrations above 10 ppb. Our new sensor is thus 20 times more sensitive than our previous device. At concentrations greater than 10 ppb, the response of the 'non-imprinted' sensor to geosmin, another odorant often accompanying MIB, was significantly higher than the response of the 'imprinted' sensor. A number of other odorants were examined and, as in our previous work, the responses of the 'non-imprinted' sensors were found to be to greater than the responses of the 'imprinted' sensors. PMID- 11219755 TI - Surface plasmon resonance based pesticide assay on a renewable biosensing surface using the reversible concanavalin A monosaccharide interaction. AB - A competitive immunoassay based on surface plasmon resonance (SPR) for the detection of the pesticide 2,4-dichlorophenoxyacetic acid (2,4-D) is reported. The novelty of the assay is based on the regeneration of the chip surface by the reversible interaction between monosaccharide (D-glucose) and lectin (Concanavalin A). Concanavalin A-2,4-D conjugate was chemically synthesized, purified and used for binding to the SPR chip modified with covalently bound alpha-D-glucose. The interaction between anti-2,4-D antibody and the surface bound concanavalin A-2,4-D conjugate was monitored by surface plasmon resonance and the response was used for the quantification of 2,4-D. The dynamic range of the calibration curve was between 3 and 100 ng/ml. The demonstrated principle of surface regeneration based on the reversible sugar-lectin interaction may be of more general applicability in immunoassays. PMID- 11219756 TI - A liquid crystal pixel array for signal discrimination in array biosensors. AB - A new optical design uses a liquid crystal pixel array (LCPA) to discriminate multiple fluorescence signals on a two-dimensional biosensor array. The LCPA can selectively control the transmission of fluorescence generated from multiple biosensing elements on a planar waveguide. This device sequentially acquires the fluorescence data from the substrate by making multiple individual measurements of the sensing elements on the waveguide. The biosensing elements are patterned according to the pixel layout of the LCPA and optically aligned so that each electronically driven pixel can either transmit or filter out the fluorescence signal as specified by the user. The primary advantage of this system is that a single detection channel (i.e. photomultiplier tube (PMT)) can be used to measure multiple fluorescence signals from a two-dimensional substrate while the LCPA provides for spatial resolution. We evaluate the performance of the LCPA by testing the optical homogeneity of the liquid crystal pixels and linear dynamic range for transmitting light. The LCPA is also used with well-developed biosensing chemistry modified for this optical format. PMID- 11219757 TI - Simplified subjective workload assessment technique. AB - Although the subjective workload assessment technique (SWAT) has been widely used, it has two main problems: it is not very sensitive for low mental workloads and it requires a time-consuming card sorting pretask procedure. In this study are presented five variations of SWAT in an effort to overcome the limitations. Four of the variants used the continuous SWAT subscales while one used the discrete SWAT subscale. Fifteen subjects participated in the experiment. The scales were compared with the original SWAT scale in terms of sensitivity and pretask procedure completion time when performing arithmetic tasks. The results show that all four variants are more sensitive than the conventional SWAT scale and that the pairwise comparison procedure takes significantly less pretask completion time compared with the original SWAT scale. Thus, the conventional pretask procedure can be replaced by a simple unweighted averaging to yield a scale of high sensitivity. PMID- 11219758 TI - Effect of strenuous live-fire drills on cardiovascular and psychological responses of recruit firefighters. AB - The study examined the effects of repeated strenuous live-fire drills on cardiovascular and psychological responses of male recruit firefighters (n = 7). Participants performed three trials of a standardized set of tasks while inside a training structure containing several live fires. Measurements of heart rate, aortic blood flow, perceived exertion, respiratory and thermal distress, reaction time, and error rate were obtained before testing, after each trial and during recovery. Heart rate increased significantly during each of the trials, reaching age-predicted maximal values. Stroke volume was significantly lower after trial 3 versus trial 1 and prevalues. Perceived exertion, respiratory distress, and thermal distress all increased, indicating greater stress following firefighting activities. Reaction time and error rate did not change significantly, but there was a tendency for more errors following trials 2 and 3 versus trial 1. The training drills resulted in considerable physiological and psychological strain, which has the potential to impair cognitive function. Firefighters are encouraged to take all possible steps to mitigate the extent of the cardiovascular strain. PMID- 11219759 TI - A critical examination of perceptual and cognitive effects attributed to full spectrum fluorescent lighting. AB - Full-spectrum fluorescent lighting (FSFL) has been credited with causing dramatic improvements in vision, perception and cognitive performance as compared with other fluorescent lamp types. These effects are hypothesized to occur because of similarity between FSFL emissions and daylight, which is said to have evolutionary superiority over other light sources. This review, covering 1945-98, critically considers the evidence for these claims. In general, poor-quality research has resulted in an absence of simple deterministic effects that can be confidently attributed to fluorescent lamp type. Promising avenues for lighting behaviour research include investigations of cognitive mediators of lighting behaviour relationships, and flicker rates and colour rendering effects on visual processing, appearance judgements and affect. Good lighting solutions are more complex than lamp type specification. PMID- 11219760 TI - Low back joint loading and kinematics during standing and unsupported sitting. AB - The aim was to examine lumbar spine kinematics, spinal joint loads and trunk muscle activation patterns during a prolonged (2 h) period of sitting. This information is necessary to assist the ergonomist in designing work where posture variation is possible -- particularly between standing and various styles of sitting. Joint loads were predicted with a highly detailed anatomical biomechanical model (that incorporated 104 muscles, passive ligaments and intervertebral discs), which utilized biological signals of spine posture and muscle electromyograms (EMG) from each trial of each subject. Sitting resulted in significantly higher (p<0.001) low back compressive loads (mean +/- SD 1698 +/- 467 N) than those experienced by the lumbar spine during standing (1076 +/- 243 N). Subjects were equally divided into adopting one of two sitting strategies: a single 'static' or a 'dynamic' multiple posture approach. Within each individual, standing produced a distinctly different spine posture compared with sitting, and standing spine postures did not overlap with flexion postures adopted in sitting when spine postures were averaged across all eight subjects. A rest component (as noted in an amplitude probability distribution function from the EMG) was present for all muscles monitored in both sitting and standing tasks. The upper and lower erector spinae muscle groups exhibited a shifting to higher levels of activation during sitting. There were no clear muscle activation level differences in the individuals who adopted different sitting strategies. Standing appears to be a good rest from sitting given the reduction in passive tissue forces. However, the constant loading with little dynamic movement which characterizes both standing and sitting would provide little rest/change for muscular activation levels or low back loading. PMID- 11219761 TI - Dynamic biomechanical model of the hand and arm in pistol grip power handtool usage. AB - The study considers the dynamic nature of the human power handtool operator as a single degree-of-freedom mechanical torsional system. The hand and arm are, therefore, represented as a single mass, spring and damper. The values of these mechanical elements are dependent on the posture used and operator. The apparatus used to quantify these elements measured the free vibration frequency and amplitude decay of a known system due to the external loading of the hand and arm. Twenty-five subjects participated in the investigation. A full factorial experiment tested the effects on the three passive elements in the model when operators exerted maximum effort for gender, horizontal distance (30, 60, 90 cm), and vertical distance (55, 93, 142 190 cm) from the ankles to the handle. The results show that the spring element stiffness and mass moment of inertia changed by 20.6 and 44.5% respectively with vertical location (p<0.01), and 23.6 and 41.2% respectively with horizontal location (p<0.01). Mass moment of inertia and viscous damping for males were 31.1 and 38.5% respectively greater than for females (p<0.01). Tool handle displacement and hand force during torque build-up can, therefore, be predicted based on this model for different tool and workplace parameters. The biomechanical model was validated by recalling five subjects and having them operate a power handtool for varying horizontal distances (30, 60, 90 cm), vertical distances (55, 93, 142 cm), and two torque build-up times (70, 200 ms). Tool reaction displacement was measured using a 3D-motion analysis system. The predictions were closely correlated with these measurements (R = 0.88), although the model underpredicted the response by 27%. This was anticipated since it was unlikely that operators used maximal exertions for operating the tools. PMID- 11219762 TI - Surface electromyography analysis in long-term recordings: application to head rest comfort in cars. AB - Analysis of long-term surface electromyographic (SEMG) signals has many applications in ergonomics when related to muscle fatigue. The present work proposes a set of processing methods reporting SEMG modifications during long term driving tests in various situations (with or without head rest). A segmentation/classification algorithm allows signal splitting into homogeneous parts (postural activity and EMG bursts) and an efficient artefact suppression. Postural activity modifications are evaluated from time-varying amplitude probability density function (TAPDF) parameters. EMG burst analysis is achieved taking into account the relationships of these bursts with accelerometric events. This segmentation/classification procedure improves repeatability but does not significantly modify the overall results obtained before segmentation, as far as the analysis of head rest influence is concerned. PMID- 11219763 TI - A study of the discriminability of shape symbols by the foot. AB - An experiment to test the discriminability of shape symbols using the shod foot was performed with 38 blind people (aged 23-72 years). Ten shape symbols which were 5 mm thick and fitted into a 30.5 cm2 tile were presented to subjects to identify by using only their feet. Each subject had 20 trials in which to discriminate the symbols. In each trial, a symbol was selected randomly and presented to the subject in randomized orientation. The subject was instructed to step on the symbol and to identify it using their own method. Time to discriminate a symbol and the accuracy of identification were recorded. A very high accuracy (93% on average) was obtained, which is comparable to the accuracy of tactile symbol discrimination using the hands. Average time to discriminate a symbol was 16 s with a standard deviation of 12.15 s, which indicated the high variability of the results. Owing to the high accuracy of identification, tactile foot-discriminable symbols have great potential as landmarks for blind people and if applied to a tactile guide path they could provide information for orientation and navigation. PMID- 11219764 TI - Trapezius muscle activity as a risk indicator for shoulder and neck pain in female service workers with low biomechanical exposure. AB - Electromyographic activity of the upper trapezius muscles was recorded over the workday for two groups of service workers, shopping centre (n = 22) and healthcare workers (n = 44), both with low observed biomechanical exposure. Static and median EMG activity level, number of EMG gaps and gap time were determined. The variability of these variables over the workday was examined by calculating the coefficient of variation (CV) and the intraclass correlation coefficient (ICC) of 1-h consecutive recording periods. All variables except gap time showed acceptable reliability (ICC = 0.69-0.78), i.e. the largest fraction of variance in the data set was due to intersubject variance, despite relatively large hour-to-hour variation (CV = 0.21 0.62). The EMG activity level in the trapezius muscles was low (static activity level < 1% EMGmax), despite the high prevalence of shoulder and neck pain for both groups of workers. In addition to the work recordings, tests were performed to determine intersubject variation in muscle activity when adopting a standardized resting posture, and in a dynamic muscle activity pattern during paced arm movement. Neither the EMG variables from the work recordings nor the tests with EMG recording indicated higher trapezius EMG activity levels for workers with pain in the shoulders and neck in this study. The low EMG levels are interpreted to indicate a low risk of developing shoulder and neck complaints due to biomechanical exposure for both groups of workers. The possibility of pain-initiating mechanisms, associated with stress and not mediated through muscle activity, is considered in the discussion. PMID- 11219765 TI - High-risk human papillomavirus is sexually transmitted: evidence from a follow-up study of virgins starting sexual activity (intercourse). AB - Genital human papillomavirus (HPV) infection is generally considered to be sexually transmitted. However, nonsexual spread of the virus has also been suggested. The goal of this study was to assess: (a) the role of sexual intercourse in the transmission of HPV; (b) the determinants for seroconversion; and (c) the correlation between HPV DNA, abnormal cervical cytology, and serological response to HPV16. One hundred virgins and 105 monogamous women were randomly selected from a population-based cohort study in Copenhagen, Denmark, in which the women were examined twice with 2-year interval (interview, cervical swabs, Pap smear, blood samples). The presence of HPV DNA was determined by GP5+/6+ primers based HPV-PCR-EIA. HPV 16 virus-like particles (VLP) antibodies were detected by ELISA. All of the virgins were both HPV DNA negative and seronegative to VLP16, except for one woman who was weakly HPV 6 DNA positive. Only those virgins who initiated sexual activity became HPV DNA positive and/or VLP16 positive. The most important determinant of HPV DNA acquisition was the number of partners between the two examinations. The only significant risk factor for HPV 16 VLP seroconversion among women acquiring HPV DNA was HPV type. Our results show that sexual intercourse is important in the transmission of HPV, and that HPV 16 VLP seroconversion and the development of cervical lesions only occur after HPV transmission. Remarkably, no cervical lesions were found in HPV 16 DNA positive women who had seroconverted. Although based on small numbers, this may suggest that the development of antibodies had a protective effect. PMID- 11219766 TI - Screening markers for chronic atrophic gastritis in Chiapas, Mexico. AB - Intestinal-type gastric adenocarcinomas usually are preceded by chronic atrophic gastritis. Studies of gastric cancer prevention often rely on identification of this condition. In a clinical trial, we sought to determine the best serological screening method for chronic atrophic gastritis and compared our findings to the published literature. Test characteristics of potential screening tests (antibodies to Helicobacter pyloni or CagA, elevated gastrin, low pepsinogen, increased age) alone or in combination were examined among consecutive subjects enrolled in a study of H. pylori and preneoplastic gastric lesions in Chiapas, Mexico; 70% had chronic atrophic gastritis. English-language articles concerning screening for chronic atrophic gastritis were also reviewed. Sensitivity for chronic atrophic gastritis was highest for antibodies to H. pylori (92%) or CagA, or gastrin levels >25 ng/l (both 83%). Specificity, however, was low for these tests (18, 41, and 22%, respectively). Pepsinogen levels were highly specific but insensitive markers of chronic atrophic gastritis (for pepsinogen I <25 microg/l, sensitivity was 6% and specificity was 100%; for pepsinogen I:pepsinogen II ratio <2.5, sensitivity was 14% and specificity was 96%). Combinations of markers did not improve test characteristics. Screening test characteristics from the literature varied widely and did not consistently identify a good screening strategy. In this study, CagA antibodies alone had the best combination of test characteristics for chronic atrophic gastritis screening. However, no screening test was both highly sensitive and highly specific for chronic atrophic gastritis. PMID- 11219767 TI - Familial occurrence of nonmedullary thyroid cancer: a population-based study of 5673 first-degree relatives of thyroid cancer patients from Norway. AB - The purpose of this study was to estimate the occurrence of familial nonmedullary thyroid cancer (FNMTC) in a large population-based study. Of the 5274 cases of thyroid cancer on record in the Norwegian Cancer Registry between 1960 and 1995, a total of 1025 patients could be identified with verified thyroid cancer, a unique personal identification number, and a link to at least one parent. For patients with nonmedullary carcinoma, 5457 first-degree relatives in 970 families were found, compared with 216 first-degree relatives in 37 families for the medullary cancers. A standardized incidence ratio (SIR) was calculated among the relatives based on rates from the Cancer Registry of Norway. A significantly increased risk of thyroid cancer was found among the 5457 relatives of nonmedullary index cases, both for males [SIR, 5.2; confidence interval (CI), 2.1 10.7; 7 cases] and females (SIR, 4.9; CI, 3.0-7.7; 19 cases). All of these 26 thyroid cancer cases were of the nonmedullary type. Furthermore, an increased risk was found among 4282 relatives of papillary index cases, for both males (SIR, 5.8; CI, 2.1-12.6; 6 cases) and females (SIR, 4.0; CI, 2.1-7.1; 12 cases). The 36 familial papillary thyroid cancer patients had an average age at diagnosis of 43 years. Genetic influence is probably only modest for the familial nonmedullary cases and clearly weaker than for the classic familial type of medullary thyroid cancer. PMID- 11219769 TI - DNA repair gene XRCC1 polymorphisms, smoking, and bladder cancer risk. AB - Bladder cancer is the sixth most common cancer in the United States. The main identified risk factor is cigarette smoking, which is estimated to contribute to up to 50% of new cases in men and 20% in women. Besides containing other carcinogens, cigarette smoke is a rich source of reactive oxygen species (ROS) that can induce a variety of DNA damage, some of which is repaired by the base excision repair (BER) pathway. The XRCC1 gene protein plays an important role in BER by serving as a scaffold for other repair enzymes and by recognizing single strand DNA breaks. Three polymorphisms that induce amino acid changes have been found in codon 194 (exon 6), codon 280 (exon 9), and codon 399 (exon 10) of this gene. We tested whether polymorphisms in XRCC1 were associated with bladder cancer risk and whether this association was modified by cigarette smoking. Therefore, we genotyped for the three polymorphisms in 235 bladder cancer cases and 213 controls who had been frequency matched to cases on age, sex, and ethnicity. We found no evidence of an association between the codon 280 variant and bladder cancer risk [odds ratio (OR), 1.2; 95% confidence interval (CI), 0.6 2.6]. We found some evidence of a protective effect for subjects that carried at least one copy of the codon 194 variant allele relative to those homozygous for the common allele (OR, 0.59; 95% CI, 0.3-1.0). The combined analysis with smoking history suggested a possible gene-exposure interaction; however, the results were not statistically significant. Similarly, for the codon 399 polymorphism, our data suggested a protective effect of the homozygous variant genotype relative to carriers of either one or two copies of the common allele (OR, 0.70; 95% CI, 0.4 1.3), and provided limited evidence, albeit not statistically significant, for a gene-smoking interaction. PMID- 11219770 TI - Differential interactions between GSTM1 and NAT2 genotypes on aromatic DNA adduct level and HPRT mutant frequency in lung cancer patients and population controls. AB - We have studied the influence of GSTM1 and NAT2 genotypes on aromatic DNA adduct level (AL) and HPRT mutant frequency (MF) in smokers with newly diagnosed lung cancer and matched population controls. AL was analyzed in relation to genotypes in 170 cases and 144 controls (113 current/recent smokers and 201 former/never smokers), and MF in 157 cases and 152 controls (155 ever smokers and 154 never smokers). Both genotypes exhibited the a priori expected effects on AL and MF among controls only, especially among smoking controls [significantly lower pack years (a pack-year is defined as 1 pack of cigarettes/day for 1 year) than among cases]. Among the 42 currently smoking controls, the NAT2 slow genotype [odds ratio (OR), 7.5; 95% confidence interval (CI), 1.5-38.4], in particular in combination with the GSTM1 null genotype (OR, 19.3, 95% CI, 1.1-338.6 for null/slow versus positive/rapid) was strongly associated with high AL. The null/slow combination was also significantly associated with high MF among ever smokers (cases and controls pooled) with lower pack-years (OR, 3.7; 95% CI, 1.3 10.7 versus all of the other genotypes; OR, 5.1; 95% CI, 1.2-22.4 versus positive/rapid). In contrast, an antagonistic gene-gene interaction was seen among smoking cases for both AL and MF. Only currently smoking cases with the combined GSTM1 null and NAT2 rapid genotype showed a positive correlation between InAL and InMF (r, 0.64; P = 0.1), and an increase of AL with both age and daily cigarette use. This genotype combination was also associated with high MF among ever-smoking cases (OR, 4.0; 95% CI, 0.9-17.7 versus positive/rapid). There was a significant interaction between NAT2 genotype and pack-years of smoking among cases, so that the rapid genotype was associated with high MF among ever-smoking cases diagnosed at higher pack-years, whereas the slow genotype was associated with high MF at lower pack-years. These findings suggest that the influence of NAT2 genotype on AL and MF and its interaction with GSTM1 genotype may be dose dependent. The NAT2 slow genotype, in particular when combined with the GSTM1 null genotype, may confer increased susceptibility to adduct formation, gene mutation, and lung cancer when the smoking dose is low. PMID- 11219768 TI - Polymorphisms of the DNA repair gene XRCC1 and lung cancer risk. AB - We explored the association between polymorphisms of the DNA repair gene XRCC1 (codons 194, 280, and 399) and lung cancer risk in a case-control study nested within a cohort of tin miners. Cases were those diagnosed with lung cancer over 6 years of follow-up (n = 108). Two controls, matched on age and sex, were selected for each case by incidence density sampling. Of the three polymorphisms, only the XRCC1 Arg280His allele was associated with increased lung cancer risk (odds ratio, 1.8; 95% confidence interval, 1.0-3.4) after adjustment for radon and tobacco exposure. In addition, individuals with the variant Arg280His allele who were alcohol drinkers seemed to be at higher risk for lung cancer compared with those with the homozygous wild-type genotype. Conversely, individuals with the variant Arg194Trp allele who were alcohol drinkers seemed to be at lower risk for lung cancer compared with those with the homozygous wild-type genotype. Polymorphisms of XRCC1 appear to influence risk of lung cancer and may modify risk attributable to environmental exposures. PMID- 11219771 TI - Mammographic density changes during the menstrual cycle. AB - The ability to detect small tumors is impaired in dense mammograms. It has been suggested that the sensitivity of mammograms could be lower in mammograms obtained during the luteal phase of the menstrual cycle. We examined the change in mammographic density from the follicular to the luteal phase of the menstrual cycle in 11 women. Although the average increase in densities was quite small (1.2%; P = 0.08), six women had clinically significant increases (1.4-7.8%), suggesting that premenopausal women should undergo mammographic examinations in the follicular part of the menstrual cycle. PMID- 11219772 TI - Hepatocellular carcinoma and aflatoxin exposure in Zhuqing Village, Fusui County, People's Republic of China. AB - Hepatocellular carcinoma (HCC) is a common cause of cancer morbidity and mortality in Asia and Africa. Epidemiological studies have found that dietary exposure to aflatoxin B1 (AFB1) and chronic infection with hepatitis B virus are two major risk factors for HCC. We have collated the incidence and mortality data of malignant tumors from 1973 to 1999 in Zhuqing Village, Fusui County, an area with very high HCC rates, and found that this cancer accounted for 64% of the total cancer incidence. Dietary intake of AFB1 was monitored for 1 week in a study group consisting of 15 males and 14 females from different households in this village. Four of 29 participants (13.8%) and 3 of 15 (20%) male participants were hepatitis B virus surface antigen positive. AFB1 was detectable in 76.7% (23 of 30) of ground corn samples (range, 0.4-128.1 ppb), 66.7% (20 of 30) of cooking peanut oil samples (range, 0.1-52.5 ppb), and 23.3% (7 of 30) of rice samples (range, 0.3-2.0 ppb) collected from each household. Mean levels of serum AFB1 albumin adducts in this group were 1.24 +/- 0.31 pmol/mg of albumin at the beginning of the study and 1.21 +/- 0.19 pmol/mg of albumin at the end of the period. Urinary AFB1 metabolites were detectable in 88.9% (24 of 27) samples (range, 0.9-3569.7 ng/24-h urine). These data provide the exposure and disease risk information for establishing intervention studies to diminish the impact of aflatoxin exposure in this high-risk population. PMID- 11219773 TI - Levels of 5-hydroxymethyl-2'-deoxyuridine in DNA from blood of women scheduled for breast biopsy. AB - Systemic oxidative stress is thought to contribute to risk of various cancers, including breast cancer. DNA repair ability also has been associated with breast cancer risk. In this work, we examined levels of oxidative DNA damage as an indication of breast cancer risk in women because oxidative DNA damage levels should reflect the net balance of oxidative stress and DNA repair ability. Levels of 5-hydroxymethyl-2'-deoxyuridine, one form of oxidative DNA damage, were measured in DNA from blood of women scheduled for breast biopsy. The blood samples analyzed included women whose biopsy results indicated invasive breast cancer, high-risk lesions (atypical hyperplasia or carcinoma in situ), or benign lesions. Mean levels of 5-hydroxymethyl-2'-deoxyuridine were significantly higher in blood of women who had high risk or invasive breast lesions versus women with benign lesions. If atypical hyperplasia or carcinoma in situ are precursor lesions for breast cancer, then these results suggest that oxidative DNA damage may be involved in the cancer process before invasive cancer develops. PMID- 11219774 TI - NAT2 and NQO1 polymorphisms are not associated with adult glioma. PMID- 11219775 TI - No increased Ki67 expression in ductal carcinoma in situ associated with invasive breast cancer. PMID- 11219776 TI - Germ-line p53 mutations predispose to a wide spectrum of early-onset cancers. AB - Germ-line p53 mutations are associated with dominantly inherited Li-Fraumeni syndrome (LFS), which features early-onset sarcomas of bone and soft tissues, carcinomas of the breast and adrenal cortex, brain tumors, and acute leukemias. However, carriers of germ-line p53 mutations may also be at increased risk of other cancers. To clarify the tumor spectrum associated with inherited p53 mutations, we examined cancer occurrences among our series of 45 families, plus 140 other affected cases and kindreds reported in the literature. The analyses included all cancers in patients with a germ-line p53 mutation and their first degree relatives with nearly 50% likelihood of being a carrier. Data were abstracted on tumor types and ages at diagnosis in eligible family members, and duplicate reports were excluded. Among 738 evaluable cancers, 569 (77%) were the six tumor types (breast and adrenocortical carcinomas, sarcomas of the bone and soft tissues, brain tumors, and leukemias) associated with LFS. The remaining 169 (23%) cancers included diverse carcinomas of the lung and gastrointestinal tract, lymphomas, and other neoplasms that occurred at much earlier ages than expected in the general population. Unusually early ages at diagnosis are characteristic of hereditary cancers and suggest that carriers of germ-line p53 mutations are at increased risk of a wide range of neoplasms. Future studies addressing age specific penetrance and site-specific cancer risks can increase the utility of LFS as a model for understanding the role of p53 alterations in carcinogenesis and for designing diagnostic and preventive interventions for the broad array of neoplasms in this syndrome. PMID- 11219778 TI - Evaluation of self-collected cervicovaginal cell samples for human papillomavirus testing by polymerase chain reaction. AB - As human papillomavirus (HPV) becomes accepted as the central cause of cervical cancer, longitudinal studies are shifting focus away from causality to a more detailed investigation of the natural history of HPV infections. These studies commonly require repeated samples for HPV testing over several years, usually collected during a pelvic exam, which is inconvenient to the participants and costly to the study. To alleviate the inconvenience and cost of repeated clinic visits, it has been proposed that women collect cervicovaginal cells themselves, hopefully increasing participation in the natural history studies. We evaluated the technical feasibility of self-collection of cervicovaginal cells using a Dacron swab for HPV DNA detection. We compared the self-collected swab sample and two clinician-administered swab samples (one from the endocervix and another from the ectocervix) from a total of 268 women participating in a case-control study of adenocarcinoma and squamous cell carcinomas of the uterine cervix (111 cases and 157 controls). HPV DNA was detected and genotyped using an L1 consensus PCR assay. The overall agreement between the clinician- and self-collected swabs was excellent [88.1%; kappa = 0.73 (95% confidence interval (CI), 0.61-0.85)]. The correlation was highest between the two clinician-administered swabs [kappa = 0.81 (95% CI, 0.69-0.93)] but was still excellent when comparing either clinician administered swab to the self-administered sample [kappa = 0.75 (95% CI, 0.63 0.87) and 0.67 (95% CI, 0.55-0.79) for ectocervix and endocervix, respectively]. The type-specific agreement between samples was higher for high-risk, or cancer associated, HPV genotypes than for low risk, noncancer-associated HPV genotypes when comparing the self-administered swab sample to the clinician-administered swab sample (kappa = 0.78 for high-risk versus 0.66 for low-risk HPV infections, t = -1.45, P = 0.15). The decrease in agreement for low risk types was largely attributable to an increased detection of these types in the self-administered sample (McNemar's chi2 = 6.25, P = 0.01 for clinician- versus self-administered swab comparisons). The agreement did not vary significantly by age, menopausal status, case status, or clinic center. We have demonstrated that a self-collected Dacron swab sample of cervicovaginal cells is a technically feasible alternative to clinician-administered cervical cell collection in natural history studies of HPV and cervical cancer. PMID- 11219779 TI - Defining moments in medicine. Pathology. PMID- 11219777 TI - Sulfotransferase 1A1 polymorphism, endogenous estrogen exposure, well-done meat intake, and breast cancer risk. AB - Sulfotransferase (SULT) 1A1 is involved in the inactivation of estrogens and bioactivation of heterocyclic amines and polycyclic aromatic hydrocarbons. A G-- >A transition at codon 213 (CGC/Arg to CAC/His) of the SULT1A1 gene was reported recently, and individuals homozygous for the His allele have a substantially lower activity of this enzyme than those with other genotypes. We hypothesized that the His allele may be a risk factor for breast cancer, particularly among women who had risk factors related to higher endogenous estrogen exposure. This hypothesis was investigated in a case-control study conducted in a cohort of postmenopausal Iowa women who completed a mailed questionnaire in 1986 on lifestyle factors including information on major breast cancer risk factors. DNA samples and information related to well-done meat intake were obtained from breast cancer cases diagnosed between 1992 and 1994 and a random sample of cancer free cohort members. Multivariate analysis was performed on data from 156 cases and 332 controls who donated a blood sample. The frequency of the His allele was 41.6% in cases and 34.1% in controls (P = 0.03), and the risk of breast cancer was increased with the number of His alleles (P for trend = 0.02). Compared with women with the Arg/Arg genotype, an 80% elevated risk was observed among women homozygous for the His allele (95% confidence interval, 1.0-3.2; P = 0.04). This positive association was more pronounced among women who drank alcohol and had a high body mass index, early age at menarche, and late age at menopause, factors related to high endogenous estrogen exposure, than among those who did not have these risk factors. The risk of breast cancer was elevated with increasing doneness level of red meat intake among women with the Arg/Arg genotype (P for trend, 0.01) or the Arg/His genotype (P for trend, 0.10), whereas this association was not evident for women with the His/His genotype. The results from this study suggest that homozygosity for the SULT1A1 His213 allele may be a risk factor for breast cancer, and its effect may be modified by the exposure level of endogenous estrogens and heterocyclic amines. PMID- 11219780 TI - Defining moments in medicine. Surgery. PMID- 11219782 TI - Defining moments in medicine. Radiology. PMID- 11219781 TI - Defining moments in medicine. Obstetrics and gynaecology. PMID- 11219783 TI - Defining moments in medicine. Paediatrics. PMID- 11219784 TI - Defining moments in medicine. Anaesthesia. PMID- 11219785 TI - Defining moments in medicine. Psychiatry. PMID- 11219786 TI - Death, disease and diversity in Australia, 1951 to 2000. AB - There has been a substantial decline in mortality in Australia during the 20th century, with a major improvement in life expectancy. There has been a broad "health transition", from a pattern of high mortality from infectious diseases to one of lower overall mortality from non-communicable diseases and injury. From 1951, trends in death rates from major causes were evident, with the rise and partial fall of two epidemics (coronary heart disease and stroke, and lung cancer). This overall picture masks significant inequalities in health for Indigenous people and the socioeconomically disadvantaged. PMID- 11219787 TI - Expansion and diversification of medical education in Australia, 1951-2000. AB - Australia's present diverse and dynamic medical education environment has been shaped by: university funding increases by governments in the 1960s and 70s to promote Australia as a "clever" country; the Karmel Report's recommendations of increases in student numbers, new medical schools and a community focus for medical education; the successful innovations in entrance requirements and curricula of the most recent medical schools -Newcastle and Flinders; the formation of the Australian Medical Council, with a mandate to replace the British General Medical Council's accreditation of and restrictions on Australian medical school courses; the Doherty Report, which identified the close relationship between medical education, funding and workforce issues; the change to graduate entry and a four-year course for several Australian medical schools; and changing patterns of healthcare delivery, the imperative for increasing access to healthcare in rural areas, and the communication revolution made possible by information technology. PMID- 11219788 TI - A half-century of Australian health and medical research. AB - In 1951, the Journal published an overview of medical research in Australia since Federation. This concluded that, with a few notable exceptions, discoveries were few and research funding was paltry. In contrast, in 2001, Australia has become a significant contributor to international medical research. Three Australians have been awarded Nobel Prizes for research performed in Australia, and others have received international awards. Research growth has been driven by the development of the tertiary education sector and independent medical research institutes. Nevertheless, there is no room for complacency. PMID- 11219789 TI - Celebrating the centenary of Federation. PMID- 11219790 TI - Half a century of healthcare in Australia. PMID- 11219791 TI - A short history of vaccination in Australia. AB - It is almost 50 years since infant vaccination for diphtheria, pertussis and tetanus became routine in Australia. Since then, the incidence of vaccine preventable diseases has declined dramatically. We have used existing records and the recollections of experts to compile a history of vaccination in Australia, focusing on vaccines in the current childhood schedule. PMID- 11219794 TI - Fifty years of medical specialisation: from foundation to fragmentation. AB - The past 50 years of medicine have been dominated by revolutions in biological sciences and clinical therapeutics. No less dramatic have been changes in our healthcare systems, with medical specialisation playing a leading role. The middle of the century saw the rapid development of the teaching hospital as the centre of professional education, collegiate identity, medical specialisation and clinical research. By contrast, the past 20 years have seen dramatic shifts in response to the demands of a more diverse community. PMID- 11219793 TI - The growth of ethics in medicine over the past 50 years. PMID- 11219795 TI - Pharmacotherapeutics: what a difference five decades makes! AB - Our ability to prevent, cure or modify disease, as compared with relieving symptoms, has changed beyond recognition in the past half century. With the completion of the Human Genome Project and rapid advances in understanding of molecular biology and in technologies, our ability to target disease mechanisms and optimise an individual's responses will improve exponentially. PMID- 11219796 TI - Women in medicine: two generations. PMID- 11219797 TI - Medical themes on Australian coins. PMID- 11219798 TI - Preoccupations of the medical profession in Australia 100 years ago. PMID- 11219799 TI - On the writing and reading of obituaries. PMID- 11219801 TI - A golden age defined. PMID- 11219802 TI - Defining moments in medicine. General practice. PMID- 11219803 TI - Defining moments in medicine. Internal medicine. PMID- 11219804 TI - Global phytochemistry: the ethnobotanist view. PMID- 11219805 TI - Investigation of avenacin-deficient mutants of Avena strigosa. AB - The biosynthesis of cyclic triterpenoids in ten saponin-deficient (sad) mutant varieties of the diploid oat Avena strigosa is reported. Two mutants were found to be deficient in 2,3-oxidosqualene:beta-amyrin cyclase (OSbetaAC) (EC 5.4.99) and thus unable to produce the beta-amyrin necessary for the production of avenacins. The other mutants studied had post beta-amyrin lesions. 2,3 Oxidosqualene:cycloartenol cyclase (OSCC) (EC 5.4.99.8) needed for sterol formation was present in all ten mutants. PMID- 11219806 TI - The study of a monocotyledon abscission zone using microscopic, chemical, enzymatic and solid state 13C CP/MAS NMR analyses. AB - We have investigated distinguishing features in cells of the abscission zone of a monocotyledon fruit, the oil palm Elaeis guineensis. The cell walls of the abscission zone and the subtending mesocarp and pedicel have been analysed by light and transmission electron microscopy, by chemical methods and by solid state 13C CP/MAS NMR spectroscopy. Results show that these abscission zone cells have specific characteristics which include high levels of unmethylated pectin in the walls and an inducible (x35) polygalacturonase enzyme expression. Together these findings help to explain the localised precision of cell separation events. PMID- 11219807 TI - The ABC-like vacuolar transporter for rye mesophyll flavone glucuronides is not species-specific. AB - In many cases, the vacuolar uptake of secondary metabolites has been demonstrated to be strictly specific for a given compound and plant species. While most plants contain glycosylated secondary substances, few cases are known where flavonoids may also carry negative charges, e.g. as glucuronide conjugates. Vacuolar transport of glucosylated phenylpropanoid derivatives has been shown to occur by proton substrate antiport mechanisms (Klein, M., Weissenbock. G., Dufaud, A., Gaillard, C., Kreuz, K., Martinoia, E., 1996. Different energization mechanisms drive the vacuolar uptake of a flavonoid glucoside and a herbicide glucoside. J. Biol. Chem. 271, 29,666-29,671). In contrast, flavone glucuronides appearing specifically in rye mesophyll vacuoles are taken up by direct energisation utilising MgATP, strongly arguing for the presence of an ATP-binding cassette (ABC) transporter belonging to the subfamily of multidrug resistance-associated proteins (MRP) on the rye vacuolar membrane (Klein, M., Martinoia, E., Hoffmann Thoma, G., Weissenbock, G., 2000. A membrane-potential dependent, ubiquitous ABC like transporter mediates the vacuolar uptake of rye flavone glucuronides regulation of glucturonide uptake by glutathione and its conjugates. Plant Journal 21, 289-304). MRPs are known to transport negatively charged organic anions. Results presented here suggest that the vacuolar directly energised MRP like glucuronate pump for plant-specific flavone glucuronides is ubiquitously present in diverse plant species since rye flavone glucuronides are taken up into vacuoles isolated from the barley mesophyll or from the broccoli stalk parenchyma representing two species which do not synthesise glucuronidated secondary compounds. According to the transport characteristics and inhibition profile observed we propose the existence of a high-capacity, uncoupler-insensitive vacuolar ABC transporter for flavone glucuronides and possibly other negatively charged organic compounds -- plant-born or xenobiotic -- irrespective of the plant's capability to endogenously produce glucuronidated compounds. PMID- 11219808 TI - In vitro inhibition of Sphaeropsis sapinea by natural stilbenes. AB - The effects of pinosylvin, pinosylvin monomethyl ether, pinosylvin dimethyl ether, and resveratrol on the fungal shoot blight and canker pathogen of conifers Sphaeropsis sapinea were examined in vitro. Effects of compounds, isolates, and concentrations on both conidial germination and mycelial growth were significant (values of P < 0.001), indicating inhibitory activity of these compounds. PMID- 11219809 TI - Bioactive humulene derivatives from Asteriscus vogelii. AB - The bioactive fractions obtained from the extract of Asteriscus vogelii afforded a new humulene derivative, the 8-oxo-6,7,9,10-tetrahydrohumulen-1,12-olide (1), in addition to the known asteriscunolides A (2), C (3) and D (4), and the acids 8 oxo-alpha-humula-6Z,9Z-dien-12-oic acid (5), 8-oxo-alpha-humula-6E,9Z-dien- 12 oic acid (6) and 8-oxo-alpha-humula-6E,9E-dien-12-oic acid (7), characterized as their methyl esters. Evaluation of their phytotoxic and cytotoxic activities was accomplished. Compounds 3 and 4 gave the highest inhibition of plant cell cultures and of the plant Lemna paucicostata. Compound 4 was also the most active against P-338 lymphoma in mice, A-549 carcinoma of human lung, HT-29 carcinoma of human colon and MEL-28 human melanoma. PMID- 11219810 TI - A new triterpenoid from the fern Adiantum lunulatum and evaluation of antibacterial activity. AB - A new triterpenoid, 22,29xi-epoxy-30-norhopane-13beta-ol (1) was isolated together with six known compounds viz., fern-9(11)-en-6alpha-ol. fern-9(11)-ene, fern-9(11)-en-25-oic acid, fern-9(11)-en-28-ol, filicenol-B, adiantone and oxidation product of fern-9(11)-en-6alpha-ol obtained as 6-oxofern-9(11)-ene from the whole plant of Adiantum lunulatum, and their structures were elucidated by means of spectroscopic analysis and antibacterial evaluation of these compounds were conducted. PMID- 11219812 TI - Further glucosides of lichens' acids from Central Asian lichens. AB - Eight compounds isolated from an extract of Central Asian lichens comprised new glucosides having murolic, protoconstipatic and allo-murolic acids as the aglycones and a saccharide moiety linked at C-18 made up of four glucoses. The structures were elucidated using extensive spectroscopic analysis (1D and 2D NMR, MS, IR, UV and CD) and by chemical methods. PMID- 11219811 TI - Diterpenoids from Azorella yareta and their trichomonicidal activities. AB - Diterpenoids with trichomonicidal activity were isolated from the aerial parts of Azorella yareta Hauman. One was 13beta-hydroxyazorellane, together with the known constituents mulinolic acid, mulin-11,13-dien-20-oic acid, azorellanol and 13alpha-hydroxyazorellane. Their structures were determined by spectroscopic and chemical methods. PMID- 11219813 TI - Polyphenolic compounds from Geranium pratense and their free radical scavenging activities. AB - Two new polyphenolic compounds, myricetin 3-O-(2"-O-galloyl)-beta-D glucopyranoside and (-)-6-chloroepicatechin, were isolated from the aerial parts of Geranium pratense subsp. finitimum (Woronow) Knuth, along with three known polyphenolic compounds [quercetin 3-O-(2"-O-galloyl)-beta-D-glucopyranoside, quercetin 3-O-(2"-O-galloyl)-beta-D-galactopyranoside, methyl gallate] and tryptophan. Quercetin 3-O-beta-D-glucopyranoside, quercetin 3-O-beta-D galactopyranoside, quercetin 3-O-(2"-O-galloyl)-beta-D-glucopyranoside and quercetin 3-O-(2"-O-galloyl)-beta-D-galactopyranoside were found to be effective against free radical induced impairment of endothelium-dependent relaxation in isolated rat aorta. PMID- 11219814 TI - Synthesis, characterisation and water sorption properties of pectin dehydrogenation polymer (lignin model compound) complex. AB - Coniferyl alcohol was polymerised in the presence of pectin and a pectin-DHP complex was isolated. Characterisation of the complex has demonstrated that DHP (20% wt) was covalently linked by ester bonds to the pectin. The water sorption behaviour of the pectin-DHP complex was determined at several relative vapour pressures and compared with those obtained on pectin, DHP and a blend of both polymers in the same proportion as in the complex. The complex exhibited a lower hydrophilicity resulting from three associated phenomena: grafting, pectin-DHP interactions and the formation of a chemical network. PMID- 11219815 TI - Terpenoids from Guarea rhophalocarpa. AB - Four new terpenes including, two sandaracopimaradiene diterpenoids, ent-8(14),15 sandaracopimaradiene-2alpha,18-diol, and ent8(14),15-sandaracopimaradiene 2beta,18-diol, and two lanostane triterpenoids, 23-hydroxy-5alpha-lanosta 7,9(11),24-triene-3-one, and 5alpha-lanosta-7,9(11),24-triene-3alpha,23-diol, were isolated from the methanolic extract prepared from the leaves of G. rhopalocarpa together with the known steroid stigmasterol and the coumarin, scopoletin. The isolates showed weak antiprotozoal activity against Leishmania donovani promastigotes, and Trypanosoma brucei brucei blood stream trypomastigotes, and were devoid of interesting activity towards Plasmodium falciparum. The isolates did not show significant cytotoxic activity against KB cells. PMID- 11219816 TI - What is your diagnosis? Gas-filled anal glands: normal variant mimicking a disease. PMID- 11219817 TI - Dental disease in chinchillas in the UK. AB - Dental abnormalities are common in chinchillas, although knowledge of the lesions responsible for the clinical signs is incomplete. Animals bred in the UK were examined to gain further knowledge of dental disease in this chinchilla population. Dental abnormalities, particularly those related to tooth elongation, were detected on careful external examination of 35 per cent of apparently healthy chinchillas. Incisor abnormalities were seen on clinical examination in 55 per cent of chinchillas presented because of clinical illness. In all but one case, this occurred secondarily to crown elongation of the cheek teeth or to the absence of opposing teeth, rather than being a primary skeletal problem. Clinical signs commonly attributed to malocclusion, such as ventral mandibular swelling, weight loss, dysphagia, altered chewing pattern and changed food preferences, were not specific to malocclusion, being seen associated with coronal spike formation, root elongation and advanced periodontal lesions. Caries and resorptive lesions rarely caused clinical signs in this population, but were identified during 37 per cent of postmortem examinations. Congenital absence of teeth, skeletal malocclusion and pathological loss of teeth all resulted in significant clinical signs, but were rare. It is concluded that provision of a diet with physical properties more closely matching that of wild chinchillas should improve the dental health of captive animals. PMID- 11219818 TI - Aortic body chemodectoma causing pulmonary oedema in a cat. AB - A seven-year-old male domestic shorthaired cat was presented with persistent dyspnoea. Thoracic radiography and echocardiography revealed pulmonary oedema and a mass at the base of the heart. At necropsy the mass was found to be an aortic body chemodectoma that had metastasised to the sternal lymph node. This is a rare tumour in the cat, the third reported case where there was evidence of metastasis, and only the second reported case where there was evidence of lymphocytic infiltration of the primary tumour. Pulmonary oedema is an unusual presentation of this tumour in the cat. PMID- 11219819 TI - Dyskinesia in an adult bichon frise. AB - Dyskinesias are disorders of the central nervous system that result in involuntary movements in a fully conscious individual. This report describes a disorder in a five-year-old male neutered bichon frise characterised by episodic involuntary skeletal muscle activity with normal levels of consciousness that bears some similarity to the previously described movement disorder in boxer puppies and to the human condition descriptively referred to as paroxysmal dystonic choreoathetosis. The disorder was differentiated from partial motor seizure activity by the character of the episodes, absence of identifiable preceding aura, absence of autonomic signs and the fact that multiple limbs were affected in a varying pattern without generalisation and loss of consciousness. Movement disorders are a well documented group of disorders in human neurology, but only rarely described in the veterinary literature. The purpose of this report is to contribute to an increased awareness of movement disorders within veterinary practice. PMID- 11219820 TI - Intrathoracic lipoma in a Labrador retriever. AB - Pyrexia, granulocytosis and hyperglobulinaemia were the main clinical findings in an unusual case of intrathoracic lipoma in a 12-year-old male Labrador retriever. The response to antibiotic and anti-inflammatory treatment was poor, prompting further investigation. Survey radiographs and ultrasonography revealed a cavitated, fluid-filled soft tissue mass in the right hemithorax, which was successfully removed resulting in rapid resolution of clinical signs. Lipomas are rare intrathoracic extrapulmonary tumours. Previously reported clinical signs are dyspnoea and coughing, attributed to the mass effect of the lipoma. The unusual presentation in this case was caused by necrosis of the lipoma, probably owing to torsion of the pedicle attaching it to the cranial mediastinum. PMID- 11219821 TI - Magnetic resonance imaging in the diagnosis and treatment of a canine spinal cord injury. AB - A nine-year-old female crossbred dog was presented with tetraplegia following a fall. No vertebral abnormalities were detectable on plain radiographs of the cervical spine. Magnetic resonance imaging scans revealed absence of extraparenchymal compression and an area of oedema within the cervical spinal cord, suggesting a favourable prognosis. Following nursing care and physiotherapy, the dog recovered the ability to walk, although mild neurological deficits persisted in the left limbs. PMID- 11219822 TI - Resolution of dysphagia following cricopharyngeal myectomy in six young dogs. AB - Six young dogs were presented with a history of dysphagia and nasal regurgitation since birth. Following cranial nerve examination and assessment of swallowing with fluoroscopy, a diagnosis of cricopharyngeal achalasia was made in each case. In four dogs, concomitant aspiration pneumonia was present. Sectioning and removal of part of the cricopharyngeal muscle resulted in immediate and continued resolution of all signs of dysphagia and nasal regurgitation over follow-up periods of two to eight years. Postoperative complications were not seen in any case. In five of the six dogs, the cricopharyngeal muscle was approached laterally, a technique not previously described. PMID- 11219823 TI - Practice in the year 2020: the shape of things to come? PMID- 11219824 TI - Immunosuppression in bitches with pyometra. AB - The function of the immune system was studied in 34 bitches affected by pyometra. The mean age of the animals was 8.1 +/- 2.8 years. Samples of peripheral blood were examined using a battery of immunological tests. Data obtained from four sets of animals, grouped according to the severity of their disease, were compared. Leucocytosis (neutrophilia and partial monocytosis) and lymphopenia were detected in 62 per cent and 35 per cent of the bitches, respectively. The increase in the number of leucocytes was higher in the severely affected bitches. Inhibition of mitogen-driven lymphocyte proliferation was the characteristic feature of the immunological profile in bitches affected by pyometra, and this corresponded with the impairment of the general state of health. Sera from bitches showing functional inhibition of lymphocytes suppressed the activity of lymphocytes isolated from normal dogs. Sera from bitches affected by pyometra also had higher levels of immunoglobulins, lysozyme and circulating immune complexes. It can be concluded that pyometra is associated with an inflammatory response, but also with a marked suppression of immune system activity. PMID- 11219825 TI - Double orthopaedics at Congress 2001. PMID- 11219826 TI - WSAVA links up with pet web site. PMID- 11219827 TI - Somatic cell hybrids of the Djungarian hamster: malignancy and evolution of the karyotype. AB - Djungarian hamster somatic cell hybrids were obtained by fusing malignant SV40 transformed fibroblasts (line DM15, HGPRT-), and normal male lymphoid cells. Tumorigenicity, growth in soft agar and karyotype changes of 10 independent hybrid clones were studied. All hybrids grew as tumors after injection of new born hamsters with 1 x 10(6) cells. A total of 313 tumors occurred in 523 hamsters. The hybrids proliferated in soft agar as well. No correlation was noted between the ability of hybrids to grow in vivo and to form colonies in soft agar. The total chromosome number in hybrid cells was usually less than the expected sum of the parental chromosome sets. G-banding analysis showed that, in vitro, hybrids lost chromosomes of the normal parent, whereas marker chromosomes of the malignant parent were retained. In the majority of hybrid tumors the chromosome set was reduced to the diploid range. In tumors with a slightly reduced karyotype one or two homologues of chromosomes #4 and #8 were, as a rule, eliminated. PMID- 11219829 TI - A method to separate the geographical components of temporal change in cancer mortality rates. AB - This communication sets forth and illustrates a method to isolate local changes in cancer mortality rates from national and regional components. The method is suggested as a means of identifying note-worthy places for case control and other local studies from large data bases with temporal and geographical dimensions. PMID- 11219830 TI - Metabolism of benzo[a]pyrene in human epidermal keratinocytes in culture. AB - The metabolism of benzo[a]pyrene (BP) in cultured human epidermal keratinocytes was investigated using thin layer chromatography, high pressure liquid chromatography and cell-mediated mutagenesis assay. Epidermal keratinocytes were obtained from skin of normal subjects and all experiments were performed on primary cultures. Human epidermal keratinocytes were shown to metabolize BP. Analysis of BP metabolites by high pressure liquid chromatography indicated that epidermal keratinocytes metabolize BP preferentially at non-K-regions such as positions 7, 8, 9 and 10, forming a moderate amount of BP-7,8-dihydrodiol, a precursor of the ultimate metabolite, BP-7,8-dihydrodiol-9,10-epoxide. Conjugate formation was examined by treating the medium with beta-glucuronidase and arylsulfatase. No appreciable amount of conjugates was formed by epidermal keratinocytes, except in one culture which gave small peaks eluted in the phenol regions after beta-glucuronidase treatment. The metabolic activity of human epidermal keratinocytes on BP was further demonstrated by a cell-mediated assay, in which V79 Chinese hamster cells were cultured on top of sheets of keratinocytes and treated with BP for 48 h. Mutation of the V79 cells, demonstrated as ouabain resistance, was induced in a dose-related fashion. The extent of induced mutation was higher than that observed using rat embryo cells as the activating layer, although the shape of the dose-response curves was different. PMID- 11219828 TI - N-acetoxy-2-acetylaminofluorene induced unscheduled DNA synthesis of granulopoietic precursor cells in chronic myeloid leukemia. AB - Studies on N-acetoxy-2-acetylaminofluorene (NA-AAF) induced unscheduled DNA synthesis (UDS) of granulopoietic cells were performed in patients with chronic myeloid leukemia (CML). Sequential studies were carried out in some patients. Both biochemical and autoradiographic methods demonstrated that [3H]dT was incorporated into nonreplicating DNA of immature granulopoietic cells after NA AAF damage and the 2 methods significantly correlated to each other (r = 0.63, n = 19). NA-AAF induced DNA synthesis was lower for myeloblasts than promyelocytes and myelocytes. Biochemically determined NA-AAF induced UDS was higher for immature granulopoietic cells in blood than in marrow. Sequential studies on granulopoietic blood cells suggested that phases of accelerated leukocytosis in CML can be preceded by increases of NA-AAF induced UDS. Whether increases in NA AAF induced UDS relates to an amplification of repair enzymatic capacity closely correlated to the cellular replication capacity, or whether it reflects an increased sensitivity to DNA damage induction and the consequences thereof, was not resolved in this study. Nevertheless these results are consistent with the hypothesis that increases in NA-AAF induced UDS signal the evolution during chronic phase CML of cell populations of increasing malignancy which escape growth control. PMID- 11219831 TI - Uptake and binding of 1-methyl-1-nitrosourea (MNU) and 1-methyl-3-nitro-1 nitrosoguanidine (MNNG) by the isolated guinea pig pancreas. AB - 1-Methyl-1-nitrosourea (MNU) and 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) are carcinogens which methylate nucleic acids and proteins and covalently modify proteins by carbamoylation (MNU) or guanidination (MNNG). Using MNU and MNNG labeled with carbon-14 in the individual carbon positions, the above reactions were quantitated in the isolated guinea pig pancreas, an organ susceptible to tumorigenesis by MNU. Freshly prepared pancreatic lobules were incubated with the labeled drugs (0.03, 0.3 and 1.0 mM) for one hour at 37 degrees C. Alkylated purines from hydrolyzed DNA were separated on Sephadex G10 and acid-soluble nuclear proteins were extracted and separated on polyacrylamide gels. Total uptake of all four labels into lobules was linear with concentration. Acid insoluble radioactivity also increased linearly except for MNNG methylation which plateaued between 0.3 and 1.0 mM. 7-Methylguanine formation by both compounds was approximately ten fold greater than 06-methylation. However, DNA modification by MNU exceeded that by MNNG, especially at the higher drug concentrations. No carbamoylation or guanidination of DNA was detected. Total binding (methylation plus carbamoylation/guanidination) to acid-extractable chromatin proteins was equivalent to DNA modification on a molar basis (approximately 0.35 and 0.08 pmol/microg for exposure to 1.0 mM MNU and MNNG, respectively). All histones were labeled by all drug preparations, with H2A being the principal site of methylation and H2B, H3 and H1 being the major targets of carbamoylation and guanidination. H4 was the least modified histone. Drug binding to cytoplasmic organelles also occurred. These results show a broad spectrum of nuclear and cytoplasmic modification of pancreatic cells by MNU and, to a smaller extent, MNNG. PMID- 11219832 TI - Selective inhibition of rat liver nuclear RNA polymerase II by actinomycin D in vivo. AB - It is well known that actinomycin D, a carcinogen, inhibits DNA-dependent RNA synthesis. The interpretation of this inhibition has been that this carcinogen binds specifically to the deoxyguanosine moiety of a DNA molecule, and thus blocks the template function. This paper presents evidence which suggests that this single mechanistic interpretation of actinomycin D action may not be adequate in eukaryotic cells. Thirty minutes after actinomycin D injection (250 microg/100 g body weight), rat liver nuclear RNA synthesis was inhibited by 81% and nucleolar RNA synthesis was inhibited by 98%. In order to determine whether this inhibition is due to an inhibition of DNA template function or of the RNA polymerase activity, the total nuclear free and engaged RNA polymerases were solubilized and the individual RNA polymerase species were partially purified by DEAE-Sephadex column chromatography. It was found that while the overall enzyme activities of RNA polymerase I and III were not affected, there was a selective inhibition of RNA polymerase II activity (42%). This result suggests that actinomycin D, like aflatoxin B1 and N-hydroxy-2-acetylaminofluorene, inhibits nuclear RNA synthesis at multiple sites; it inhibits nucleolar RNA synthesis by blocking the nucleolar DNA template function, and it inhibits messenger RNA synthesis by inhibiting at least partially the enzyme RNA polymerase II activity per se. PMID- 11219833 TI - Mutagenicity and toxicity of chromyl chloride and its vapours. AB - Chromyl chloride (CC), a liquid Cr6+ compound suspected of carcinogenic activity, was assayed for mutagenicity in the Ames reversion test. Due to its high volatility and toxic and corrosive properties, handling of CC required particular precautions. The liquid phase of CC elicited dose-related mutations in Salmonella typhimurium, strain TA100, although it had a limited range of activity because of its toxicity to the bacteria. The mutagenic potency and the toxic activity were of the same order of magnitude as all the water-soluble Cr6+ compounds so far tested. Toxic and mutagenic activities could also be clearly detected by using a variety of modifications of the Ames test in CC vapours which indicates the particular danger of this chromium compound. In analogy with the other Cr6+ compounds previously tested in this laboratory, all the effects observed were decreased in the presence of S-9 mix containing rat liver post-mitochondrial fractions. PMID- 11219834 TI - Tumorigenic action of N-n-butyl-N-formylhydrazine in mice. AB - Continuous administration of 0.04% N-n-butyl-N-formylhydrazine (BFH) in drinking water to 6-week-old randomly bred Swiss mice for life produced tumors of the lungs, preputial and clitoral glands. The tumor incidences in these three tissues of the treated animals were 87, 66, and 10%, whereas in the untreated controls they were 25, 0, and 0%, respectively. Histopathologically, the tumors were classified as adenomas and adenocarcinomas of the lungs, squamous cell papillomas and carcinomas, angio-, fibro-, and myxo- sarcomas of preputial glands and squamous cell papillomas and carcinomas of clitoral glands. N-n-Butyl-N formylhydrazine is a structural homologue of the carcinogenic N-methyl-N formylhydrazine and N-ethyl-N-formylhydrazine. These studies are integral parts of structure activity relationship inquiries. PMID- 11219835 TI - A comprehensive quantitative analysis of methylated and ethylated DNA using high pressure liquid chromatography. AB - Methods were developed for the efficient routine degradation and fractionation of ethylated and methylated DNA. Alkylated DNA was hydrolyzed by a neutral thermal method to yield 3- and 7- alkylpurines and O2-alkylcytosines. The partially apurinic DNA was separated from the bases by precipitation in 0.1 N HCl. Portions of the DNA precipitate were further hydrolyzed either by 0.1 N HCl to yield purine bases, or by enzymes to yield nucleosides and phosphotriesters. The chemical and enzymic digests were fractionated by a combination of high pressure liquid chromatography systems to yield quantitative estimates of the following products from methylated or ethylated DNA: 1-, 3-, and 7-alkyladenines, O2 alkylcytosines, 3-, O6-, and 7- alkylguanines and O2-, 3-, and O4-alkylthymines. N6-Alkyladenines, 1-alkylguanines and N2-alkylguanines were not detected and the 3- alkylcytosines were detected but not quantified. Phosphotriesters were estimated from the amounts of recovered alkyl phosphotriesters of thymidylyl (3' 5') thymidine. Using these methods, it was possible to account for 98, 81, 98, and 92% of the DNA bound alkyl groups obtained from DNA reacted with [14C]methyl methanesulfonate, [3H]ethyl methanesulfonate, N-[3H]-methyl-N-nitrosourea, and N [14C]ethyl-N-nitrosourea, respectively. The methods described provide reproducible and quantitative methods of analysis for all the known methylated or ethylated products in a single DNA sample. PMID- 11219836 TI - Induction of mouse epidermal ornithine decarboxylase activity and skin tumors by 7,12-dimethylben. AB - Application of a single large dose (3.6 micromol) or smaller weekly repeated doses (0.2 micromol) of 7,12-dimethylbenz[a]anthracene (DMBA) to the skin of CD-1 mice led to a 20 to 50-fold increase in epidermal ornithine decarboxylase (ODC) (EC 4.1.1.17) activity as well as tumor formation. Retinoic acid (0.17-68 nmol), a potent inhibitor of both the induction of ODC activity and tumor formation by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), failed to inhibit both the induction of ODC activity and tumor formation by DMBA. In contrast, 7,8 benzoflavone (367 nmol), which did not inhibit the induction of ODC activity by TPA, effectively inhibited the induction of ODC activity as well as the formation of skin tumors caused by DMBA. These results indicate that (a) the mechanism of the induction of ODC activity and tumor formation by a complete carcinogen appears to be different from that of the tumor promoter TPA, (b) DMBA-induced ODC activity may be an important component of the mechanism of DMBA carcinogenesis, and (c) the protective effect of retinoic acid on skin carcinogenesis is not universal; it inhibits skin tumor formation by some agents and not by others. PMID- 11219837 TI - Manganese inhibition of sarcoma induction by benzo[a]pyrene in rats. AB - The effects of Mn and Cr dusts upon carcinogenesis by polycyclic aromatic hydrocarbons were tested in male Fischer 344 rats. In Experiment I, rats were given i.m. injections of benzo[a]pyrene (BP, 1.2 mg), Mn dust (4.4 mg), and Cr dust (4.4 mg), alone, and in various combinations. By 100 weeks, sarcomas occurred at the injection site in 17/20 rats that received BP alone, versus 10/19 rats that received BP plus Mn dust (P < 0.05). The sarcoma incidences were 0/20 in 3 control groups that received the vehicle, Mn dust alone, or Cr dust alone, and 20/20 in rats that received BP plus Cr dust. In Experiment II, rats were given i.m. injections of BP (0.6 mg), 7,12-dimethylbenz[a]anthracene (DMBA, 0.6 mg), Mn dust (4.4 mg), and Cr dust (4.4 mg), alone, and in various combinations. Local sarcomas occurred in 17/20 rats that received BP alone, versus 5/17 rats that received BP plus Mn dust (P < 0.001). Sarcoma induction was not inhibited when BP was injected in the right thigh and Mn dust in the left thigh (sarcoma incidence = 16/20). The sarcoma incidences were 0/19 in a vehicle control group; 0/18 in 2 control groups that received Mn dust or Cr dust alone; 18/20 in rats that received BP plus Cr dust; 14/20 in rats that received DMBA alone; 17/19 in rats that received DMBA plus Mn dust; and 13/18 in rats that received DMBA plus Cr dust. These experiments show that Mn dust inhibits the carcinogenicity of BP when the Mn dust and BP are administered to rats by a single i.m. injection. Under identical conditions, Mn dust does not affect the carcinogenicity of DMBA; Cr dust does not affect the carcinogenicity of BP or DMBA. PMID- 11219838 TI - Detection of unscheduled DNA synthesis in hepatocytes isolated from rats treated with genotoxic agents: an in vivo- in vitro assay for potential carcinogens and mutagens. AB - An assay is described for the measurement of chemically-induced DNA repair in cultures of primary rat hepatocytes following in vivo treatment with genotoxic agents. Rats were exposed to chemicals then primary hepatocytes were isolated by liver perfusion and cultured with [3H]-thymidine. DNA repair was measured as unscheduled DNA synthesis (UDS) by quantitative autoradiography. Cells from control animals consistently ranged from -2 to -6 net grains (NG). Treatment of rats with 10, 1 or 0.1 mg/kg dimethylnitrosamine (DMN), i.p., yielded 36.6, 6.4 and -0.9 NG, respectively; 10 mg/kg DMN, per os (p.o.), produced 22.2 NG. Oral doses of 50 or 5 mg/kg acetylaminofluorene (AAF) yielded 14.0 and 6.4 NG, respectively. Carbon tetrachloride (CCl4) at 100 or 10 mg/kg, p.o., yielded -3.2 and -5.1 NG, respectively. Thus, dose-related increases in UDS were observed for the hepatocarcinogens DMN and AAF while vehicle controls and the hepatotoxin CCl4 produced no response. An examination of the time-course of DNA repair following DMN treatment shows a linear decline in UDS during the first 24 h post-treatment followed by a slower decline from 24 to 48 h. These results indicate that this assay is a potentially useful system for assessing the genotoxic and potential carcinogenic activity of chemicals in the whole animal. PMID- 11219839 TI - The tumour promoter TPA does not affect mutation to ouabain resistance in L5178Y mouse lymphoma cells. AB - Following treatment with ultraviolet light or ethyl methane-sulphonate mouse lymphoma L5178Y cells were cultured for different periods in the presence of non toxic levels of the tumour promoter 12-O-tetra-decanoylphorbol-13-acetate (TPA). There were no significant changes in either the spontaneous or induced frequencies of ouabain-resistant variants recovered after TPA treatment. These results confirm that any effect of TPA on mutagenesis may be by modifying metabolic cooperation and the recovery of resistant cells. PMID- 11219840 TI - Effect of methyl substitution on mutagenicity of 2-aminodipyrido. AB - The mutagenicities of 2-aminodipyrido [1,2-a:3',2'-d] imidazole (Glu-P-2, a mutagen obtained from pyrolysate of glutamic acid) and six methyl substituted derivatives of Glu-P-2 were tested with Salmonella typhimurium TA98 and TA100 with S-9 mix. Glu-P-1 (6-Me-Glu-P-2) was the strongest mutagen to TA98 and TA100. 3-Me-Glu-P-2 was weakest. The presence of a methyl group, and its position were shown to affect the mutagenicity significantly. PMID- 11219841 TI - The effect of dietary lactulose on experimental large bowel cancer. AB - The hypothesis that feeding of lactulose might reduce large bowel tumour development was tested in an animal model. One hundred rats were divided into groups fed either a standard rat diet with water 'ad libitum', or the same diet but with 3.3% lactulose added to the drinking water. Large bowel tumours were induced by weekly injections of 1,2 dimethylhydrazine (DMH). There was no significant difference between the number of tumours found in the standard diet or the lactulose-treated groups. This result does not seem to support the colonic flora - bile salt theory of large bowel carcinogenesis. PMID- 11219842 TI - Circular dichroism and proton magnetic resonance studies of dApdG modified with 2 aminofluorene and 2-acetylaminofluorene. AB - The conformational properties of 2'-deoxyadenylyl-(3'-5')-2'-deoxyguanosine (dApdG) modified by the covalent binding of the carcinogens 2-acetylaminofluorene (AAF) and 2-aminofluorene (AF) have been investigated, utilizing circular dichroism and proton magnetic resonance spectroscopy. The attachment of AF residues to the C-8 position of guanosine introduced smaller changes in the circular dichroism spectra of dApdG than the binding of AAF residues. Similarly, binding of AF residues caused lower up-field shifts for the H-2 and H-8 protons of adenine than the AAF residues. These results suggest that AF residues are less stacked with the neighboring A base in dApdG than AAF. Thus, AF residues bound on the C-8 position of guanine might induce less distortion in conformation of the modified regions than AAF residues. PMID- 11219843 TI - Investigation of covalent aflatoxin B1-DNA adducts formed in vivo in rainbow trout (Salmo gairdneri) embryos and liver. AB - The formation of covalent aflatoxin-DNA adducts has been studied in embryo and yearling stages of the rainbow trout (Salmo gairdneri). A linear relationship was found between the amount of aflatoxin B1 (AFB1) absorbed into 21-day-old eggs and the level of covalent modification of embryo DNA after exposure to 0.25 to 0.5 p.p.m. aqueous solutions of AFB1 for 1 h; higher concentrations resulted in absorption of a greater proportion of AFB1. The principal covalent product, identified after acid and enzymatic hydrolysis of isolated embryo DNA, was chromatographically identical to 2,3-dihydro-2-(N7-guanyl)-3-hydroxy aflatoxin B1. Additional AFB1 derivatives which were present are believed to be formed by chemical transformation of this product in DNA producing an aflatoxin formamidopyrimidine adduct and the metabolic activation of other aflatoxin metabolites, such as aflatoxin M1 and aflatoxin P1. Although the eggs were exposed to AFB1 for a short time, covalent modification of DNA was evident over an extended period. The highest level of covalent products was present at approximately 24 h after exposure to 0.5 p.p.m. AFB1. Ninety-six hours later, this level had decreased slightly; however, the distribution of covalent adducts had changed: formamidopyrimidine adducts now represented up to 50% of the hydrolyzed aflatoxin derivatives. A similar pattern of covalent aflatoxin derivatives was found in the liver DNA of yearling trout 10 h after the administration of 0.3 mg/kg AFB1. PMID- 11219844 TI - Some factors affecting mutant numbers in the Salmonella/microsome assay. AB - An examination has been made of some of the parameters which can affect mutant numbers in the Salmonella/microsome assay. The type of minimal media plates used for the assay and the concentration of glucose-6-phosphate, one of the co-factors necessary for mono-oxygenase action, had no effect on mutant numbers. Increases in mutated bacteria resulted from the use of (1) log-phase bacteria, (2) higher NADP concentrations than those normally recommended, and (3) higher phosphate buffer concentrations. Six mutagens, i.e., 2-acetylaminofluorene (AAF), 3,3' dichlorobenzidine (3,3'-DCB), cyclophosphamide (CY), aflatoxin B1 (AFB1), 3 methylcholanthrene (3MC) and benzo[a]pyrene (BP), all requiring mono-oxygenase activation, were studied with two Salmonella typhimurium strains, TA98 and TA100, and liver preparations from rats given different inducing agent treatments using optimum conditions. Phenobarbitone induction was generally superior to Aroclor 1254 in converting these substrates to mutagens except for the polycyclic hydrocarbon substrates. A comparison of 3-methylcholanthrene, Aroclor-1254, beta naphthoflavone or phenobarbitone as inducing agents revealed the first three of these to be equally effective in activating BP or 3MC to mutagens, whereas phenobarbitone was less active. Dual administration of 3-methylcholanthrene and phenobarbitone to rats did not result in an additive mutagenic effect using AAF, AFB1 or 3,3'-DCB as substrates, the numbers of mutant bacteria obtained being only equal to that seen with 3-methylcholanthrene alone. These differences were not due to there being different liver protein optima for the various inducing agent treatments. The foregoing results are discussed in relation to attempts to draw up a rigid protocol for mutagenicity testing. PMID- 11219845 TI - Mutagenicity of cimetidine in nitrite-enriched human gastric juice. AB - A mutagenic response was obtained in the Salmonella/microsome reversion test by preincubating sodium nitrite and cimetidine in human gastric juice from untreated individuals, or even by adding nitrite to gastric juice samples from patients receiving cimetidine. Both base-pair substitutions (strains TA1535 and TA100) and, though very weakly, also frameshift errors (TA1537, TA1538 and TA98) were induced by such reaction. Mutagenicity was not affected by S-9 mix containing rat liver homogenates, neither in the sense of activation nor of deactivation. The optimal reaction occurred at high equimolar concentrations of the two precursor compounds, under physiological pH and temperature conditions and within a short time of contact. Ascorbic acid was efficient in preventing the formation of mutagenic nitrosoderivative(s). PMID- 11219847 TI - The metabolism of the 10,11-dihydrodiol of benz[a]-anthracene to a vicinal diol epoxide that is not involved in metabolic activation. AB - Benz[a]anthracene-10,11-diol, a major metabolite of benz[a]anthracene, is metabolized by a rat-liver microsomal system to form anti-BA-10,11-diol 8, 9 oxide (t-10,r-11-dihydroxy-t-8,9-oxy-8,9,10,11 -tetrahydrobenz[a]anthracene) and, to a lesser extent, syn-BA-10,11-diol 8,9-oxide (t-10,r-11-dihydroxy-c-8,9-oxy 8,9,10,11-tetrahydrobenz[a] anthracene). However, when benz[a]anthracene is incubated with DNA in a rat-liver microsomal system, anti-BA-10,11-diol 8,9-oxide does not contribute to the covalent binding of this hydrocarbon to DNA. PMID- 11219846 TI - The relationship between alkylation of specific DNA bases and induction of sister chromatid exchange. AB - The mechanism of induction of sister chromatid exchange (SCE) was investigated by treating Chinese hamster V-79 cells with two ethylating and two methylating mutagens at doses, taken from linear response curves, that produced 30 SCE/cell. Concentrations of the DNA alkylation products were measured or calculated at 11 DNA base sites and at the phosphodiester bond. Ethyl methanesulfonate, N-methyl- and N-ethyl-N-nitrosourea produced comparable concentrations (3.3 to 3.5 micromol product/mol DNA phosphate) of O6-alkylguanine. Hence, alkylation at O6 of guanine appears relevant to SCE induction for these mutagens. Since alkylation at O6 of guanine has been positively correlated with mutagenesis in V-79 cells, these findings support the suggestion that SCE and mutagenesis can result from a common DNA lesion. Methyl methanesulfonate (MMS) produced very little O6-methylguanine, but did produce 3-methylthymine and 3-methyladenine, either of which might account for the MMS-induced SCE. Thus, for a series of mutagens, induction of SCE does not necessarily result from a single specific DNA lesion. Therefore, SCE can be considered a qualitative indicator of potential mutagenic events. PMID- 11219848 TI - Fluorescence spectral evidence that benzo[a]pyrene is activated by metabolism in mouse skin to a diol-epoxide and a phenol-epoxide. AB - Hydrolysates of DNA that had been isolated from mouse skin treated with 3H labelled benzo[a]pyrene were subjected to chromatography on Sephadex LH20. Two major products were eluted in the region expected for deoxyribonucleoside hydrocarbon adducts and these were purified further by h.p.l.c. The fluorescence emission and excitation spectra of one of the adducts were identical to that of the adduct obtained from DNA that was treated with BP-7,8-diol 9,10-oxide (r-7,t 8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a] pyrene). The fluorescence emission and excitation spectra of the other adducts were identical to the published spectra of 9-OHBP-4,5-diol (4,5-dihydro-4,5,9-trihydroxy benzo[a]pyrene) and of the deoxyribonucleoside-hydrocarbon adduct obtained from DNA that had been incubated with 9-OHBP (9-hydroxybenzo[a] pyrene) in the presence of a rat-liver microsomal system. The metabolic activation of benzo[a]pyrene in mouse skin, a target tissue for carcinogenesis by this hydrocarbon, thus appears to involve the formation of adducts derived from both BP-7,8-diol 9,10-oxide and 9-OHBP 4,5-oxide (9-hydroxybenzo-[a]pyrene 4,5-oxide), although quantitatively, the adduct derived from 9-OHBP 4,5-oxide is a minor product. PMID- 11219849 TI - Tumor promoter produces anchorage independence in mouse epidermal cells by an induction mechanism. AB - The irreversible shift in anchorage independence by phorbol ester responsive mouse epidermal cell lines appears to occur not by a mechanism involving selection of preexisting transformants but by induction of a new phenotype. PMID- 11219850 TI - Sensitivity of the conformation of deoxyguanosine to binding at the C-8 position by N-acetylated and unacetylated 2-aminofluorene. AB - The conformation of N-(deoxyguanosin-8-yl)-2-acetylaminofluorene and N (deoxyguanosin-8-yl)-2-aminofluorene was investigated by 1H n.m.r. spectroscopy. There was rotation about the glycosyl bond and preference for either the anti or syn conformation depended on whether or not the 8-arylamino nitrogen was acetylated. The unacetylated adduct existed preferentially in the anti form and the acetylated adduct existed preferentially in the alternate syn form. There was also rotation about the backbone C4' -C5' bond. The unacetylated adduct was mainly in the gauche-gauche conformation about C4'-C5', while the acetylated adduct was mainly in the alternate gauche-trans/trans-gauche form. Using space filling models with the conformation of the unacetylated adduct conserved in the helix, a possible structure of modified DNA was proposed which had less perturbation of the helix than that of the acetylated adduct. This was consistent with single strand endonuclease hydrolysis data. The acetylated and unacetylated adducts may cause entirely different types of local conformational changes in DNA because of major differences in interactions between the base and the sugar moiety at the modified nucleoside level. PMID- 11219851 TI - Antibodies to N-hydroxy-2-aminofluorene modified DNA as probes in the study of DNA reacted with derivatives of 2-acetylaminofluorene. AB - Antibodies were elicited in rabbits immunized with a mixture of methylated bovine serum albumin and N-hydroxy-2-aminofluorene reacted DNA (DNA-AF). These antibodies were used in competition radioimmunoassays (RIA) with [3H]DNA-AF as radioactive antigen and different N-acetoxy-2-acetylaminofluorene (N-AcO-AAF) and N-hydroxy-2aminofluorene (N-OH-AF) reacted DNAs, deoxyguanosine, dGMP, dGpA and dApG as inhibitors. Based on the results of RIA it is concluded that the binding sites of the two residues, -AF and -AAF, to guanosine in DNA, are essentially the same. Moreover, the same sites seem to be reactive also in the direct reaction of N-AcO-AAF with dGMP. Circular dichroism measurements of modified DNA confirm the RIA results. PMID- 11219852 TI - Alteration by phenobarbital of membrane-associated enzymes including gamma glutamyl transpeptidase in mouse liver neoplasms. AB - Administration of phenobarbital for 5 to 7.5 weeks to aged C3HfB/HeN mice with spontaneous liver tumors produced an enhancement of gamma glutamyl transpeptidase activity in the tumors and a decrease in glucose-6-phosphatase and adenosine triphosphatase activity. Discontinuation of phenobarbital feeding for 5.5 weeks resulted in the loss of gamma glutamyl transpeptidase activity in tumors. These findings of alterations in three membrane-associated enzymes indicate that phenobarbital produces substantial changes in the composition of cellular membranes which may be related to its promoting activity. PMID- 11219853 TI - Hydroxyurea: protection of KB cells against the toxic effect of N-methyl-N'-nitro N-nitrosoguanidine. AB - This report shows that hydroxyurea (HU) protected KB cells specifically against the toxic effect of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). It appears unlikely that this action was due to stimulation of DNA repair since HU neither protected the cells when added after removal of MNNG, nor shielded them against the toxicity of other DNA damaging agents. Similarly, it seems difficult to account for HU protection by its specific effect as an inhibitor of DNA synthesis, because cell protection was found to be maximal when the proliferative activity of the cultures was minimal, and because much higher doses of HU were required to ensure cell protection than to inhibit DNA synthesis. In fact, the shift of the MNNG dose-response curves in the presence of increasing HU concentrations suggests that HU might interfere with the MNNG-molecule. This was confirmed by our finding that HU enhanced the decomposition rate of MNNG, as did other substances like cysteine or ascorbic acid, which also appeared able to protect the cells against the toxic effect of MNNG. PMID- 11219854 TI - Monooxygenase, epoxide hydrolase, and glutathione-S-transferase activities in human lung. Variation between groups of bronchogenic carcinoma and non-cancer patients and interindividual differences. AB - Activities of microsomal monooxygenases (MO) and epoxide hydrolase (EH) and cytoplasmic glutathione-S-transferases (GST) will contribute to controlling the pool of reactive intermediates, enzymatically derived from polynuclear aromatic hydrocarbons (PAH) within the cells of target organs such as the human lung. Therefore, we studied what interindividual differences exist in these enzyme activities and whether there is a correlation between the activities of these epoxide forming and metabolizing enzymes in preparations from peripheral lung samples and the occurrence of bronchogenic carcinomas in smokers and non-smokers. 57 samples obtained from surgery were studied. Among them were 12 samples from non-smoking patients without cancer as a control group. It is not known whether this control group behaves, with respect to the investigated parameters, identically to fully healthy people, since in all cases indications existed which justified the removal of lung biopsies. Using very sensitive standard assays with benzo[a]pyrene, biphenyl, 7-ethoxyresorufin and 7-ethoxycoumarin as substrates, MO activity could only be determined as O-deethylation of 7-ethoxycoumarin and only after modification of the assay method. Evidence was obtained for the presence of a diffusible, but not dialysible, MO inhibitor in human lung microsomes. The MO activity (substrate: 7-ethoxycoumarin) in this fraction was extremely low in human (100-fold lower than in rat lung preparations), whereas EH (substrate: benzo[a]pyrene 4,5-oxide) was slightly (about 2-fold) higher in human and GST (substrate: 2,4-dinitrochlorobenzene) had similar activities in both species. Interindividual variations of enzyme activities in human lung were considerable: MO, 40-fold: EH, 5-fold; GST 10-fold. Compared to the control group (non-smokers without cancer) MO activities were slightly but significantly higher in lungs from bronchogenic carcinoma patients whether they were smokers (170% of controls, p < 0.0005) or non-smokers (320% of controls p < 0.025). MO activities of smokers without cancer were only very slightly elevated (140%) of controls, p < 0.05). Specific EH activities compared to the control group were slightly but significantly increased in smokers without cancer (160% of controls, p < 0.0125) and in bronchogenic carcinoma patients whether they used tobacco products (130% of controls, p < 0.005) or not (140% of controls, p < 0.05). Specific GST activities showed no significant differences (p > 0.1) between the various groups studied. The substrate specificity of human lung EH, which was studied using five K-region epoxides of various PAH as substrates, corresponded to that in human and rat liver and in human, mouse and rat skin and to the pure enzyme isolated from rat liver. In contrast to rat liver hepatoma preparations, where EH had been shown to be increased in the tumor tissue and had been identified as a preneoplastic antigen, EH activity in lung microsomal preparations from samples of peripheral squamous cell carcinomas of two subjects had in the tumor tissue only one third of the activity of non-diseased areas of the same lung. PMID- 11219855 TI - Cleavage of lambda repressor and induction of recA protein synthesis elicited by aflatoxin B1 metabolites in Escherichia coli. AB - In Escherichia coli lambda lysogens incubated with activated aflatoxin B1, the rate of synthesis of RecA protein is markedly increased while lambda repressor is cleaved, but not that of the non-inducible mutant lambdacIind-. Following a 10 min lag period, lambda repressor is almost totally cleaved within 40 min of incubation. Cleavage of lambda repressor is inhibited by chloramphenicol. Synthesis of RecA protein and cleavage of lambda repressor are two characteristic processes induced in E. coil by DNA damaging agents such as u.v. light or mitomycin C. Our results favour the idea that in aflatoxin B1-treated lysogens, DNA lesions activate RecA protein to cleave LexA protein, the repressor of the recA gene, and lambda repressor. DNA damage, which may represent a relatively small fraction of the total cellular lesions, promotes the derepression of specific genes that control epigenetic as well as genetic processes in bacteria. PMID- 11219856 TI - Reaction of N-n-butyl-N-nitrosourea with DNA in vitro. AB - N-n-[1-14C]Butyl-N-nitrosourea was synthesized from n-[1-14C]butanol and incubated at physiological conditions (pH 7.2; 37 degrees C) with calf thymus DNA in vitro. Following mild acid hydrolysis, purine bases were separated by Sephadex G-10 and cation exchange chromatography. 3-n-Butyladenine, 7-n-butylguanine and O6-n-butylguanine were identified as major reaction products. The O6-/7 butylguanine ratio was 0.69, indicating that the relative extent of oxygen alkylation by n-butylnitrosourea is similar to that produced by ethylnitrosourea. PMID- 11219857 TI - Metabolic activation of 3-methylcholanthrene in mouse skin: fluorescence spectral evidence indicates the involvement of diol-epoxides formed in the 7,8,9,10-ring. AB - Hydrolysates of DNA that had been isolated from mouse skin treated with 3H labelled 3-methylcholanthrene were subjected to chromatography on Sephadex LH20 columns and 3H-labelled products that eluted in the region expected for nucleoside-hydrocarbon adducts were purified further by high pressure liquid chromatography; eight major and one minor products were resolved and their fluorescence spectra were determined using photon-counting spectrophotofluorimetry. The fluorescence spectra of six of the major products are anthracene-like and are similar to the previously-reported spectrum of 7,8,9,10-tetrahydro-3-methylcholanthrene, a result that is consistent with metabolic activation involving diol-epoxide formation in the 7,8,9,10-ring of 3 methylcholanthrene. The fluorescence spectra of the other two major products are also anthracene-like, but their maxima are shifted to longer wavelengths relative to the maxima in the spectrum of 7,8,9,10-tetrahydro-3-methylcholanthrene. The minor product possesses a fluorescence spectrum that is not anthracene-like and that is dissimilar from the spectra of products formed from 3-methylcholanthrene 11,12-oxide. PMID- 11219858 TI - Preferential methylation of target organ DNA by the oesophageal carcinogen N nitrosomethylbenzylamine. AB - Male Wistar rats received a single i.v. injection of the oesophageal carcinogen N nitroso[methyl-14C]-methylbenzylnitrosamine (2.5 mg/kg body weight). Rapid distribution of the carcinogen occurred, with highest initial concentrations in liver and kidney. Within 10 min after the injection, 14C-labelled metabolites accounted for 50% of the total radioactivity present in the oesophagus, for approximately 25% in liver and forestomach, and for less than 20% in all other organs investigated. Decay of the carcinogen in rat serum followed first-order kinetics with a half-life of 35 min. Of the total radioactivity administered, 49% was exhaled as 14CO2 within 10 h and an additional 5-10% was excreted via urine and faeces. Four hours after a single i.v. injection of N-nitroso-[methyl 14C]benzylnitrosamine methylation of purine bases in DNA was most extensive in the oesophagus, followed by liver, lung and forestomach DNA. In the remaining tissues, DNA methylation was either considerably less (kidney, glandular stomach, spleen) or not at all detectable (ileum, colon, brain). At this time the concentration of the promutagenic base O6-methylguanine in oesophageal DNA was six times higher than in lung and nine times higher than in hepatic DNA. These data suggest that in the rat the selective induction of oesophageal tumours by N nitrosomethylbenzylamine and related asymmetrical nitrosamines is mediated by a preferential bioactivation of the carcinogen in the target organ. PMID- 11219859 TI - Mutagenicity in Salmonella typhimurium of N-3-methylbutyl-N-1-methyl-acetonyl nitrosamine and N-methyl-N-benzylnitrosamine, N-nitrosation products isolated from corn-bread contaminated with commonly occurring moulds in linshien county, a high incidence area for oesophageal cancer in Northern China. AB - Two synthetic N-nitrosamines (N-3-methylbutyl-N-1-methyl acetonylnitrosamine and N-methyl-N-benzylnitrosamine), previously isolated from corn-bread which had been inoculated with moulds occurring in Linshien county, Northern China and subsequent nitrosation by sodium nitrite, were tested in Salmonella typhimurium strains TA1535 and TA100 in the presence of a liver postmitochondrial supernatant from Aroclor-treated rats. A concentration-dependent increase in the number of mutant colonies in both bacterial strains was observed when N-3-methylbutyl-N-1 methylacetonyl-nitrosamine was assayed in liquid suspension and N-methyl-N benzylnitrosamine in plate incorporation assays. Our finding that mutagenic N nitrosamines are present in foodstuffs that may be consumed in Linshien county are discussed in relation to the possible etiological role of these compounds in cancer of the oesophagus in that area. PMID- 11219860 TI - Metabolic activation of benzo[a]pyrene by a human hepatoma cell line. AB - The liver-derived human cell line, Hep G2, has high benzo[a]pyrene-metabolizing activity and converts benzo[a]pyrene to intermediates that are mutagenic and that bind to DNA. This cell line will be useful for studying metabolic activation of polycyclic aromatic hydrocarbons and other xenobiotics by human tissue and as an activation system in short-term screening assays for identifying compounds with carcinogenic potential for humans. PMID- 11219861 TI - Correlation of nucleic acid binding by metabolites of trans-4-aminostilbene derivatives with tissue specific acute toxicity and carcinogenicity in rats. AB - The reaction with macromolecules was determined in various tissues of female Wistar rats 24 h following a single oral administration of [3H]-trans-4 dimethylamino- and [3H]-trans-4-acetylaminostilbene. Total binding to proteins was 4-9 times greater than to nucleic acids in most tissues. Binding to RNA and DNA was very similar and greatest in liver, about 1/4 in kidney and 1/8 - 1/10 in lung, glandular stomach (target tissue for acute toxicity), bladder, mammary glands and Zymbal glands (target tissue for carcinogenicity). The target tissues, therefore, appear not to be notably exposed to reactive metabolites. The pattern of adducts was analyzed by Sephadex LH20 chromatography of RNA and DNA hydrolysates from liver, glandular stomach, lung and kidney. It was found to be very similar qualitatively. DNA-bound metabolites were very persistent in the non target tissues liver and kidney, t 1/2 being 34 and 60 days, respectively. Some of the major adducts in liver were not eliminated at all within 4 weeks. It thus appears that aminostilbene derivatives represent examples of strong and genotoxic carcinogens for which the extent and persistence of primary DNA lesions are not correlated with the biological effect. PMID- 11219862 TI - Retinoids inhibit 2,3,7,8-tetrachlorodibenzo-p-dioxine-induced activity of benzo[a]pyrene metabolizing enzymes in human diploid fibroblasts. AB - Retinoids are known to inhibit the substrate mediated enzyme induction of benzo[a]pyrene metabolizing enzymes. Consequently, the effect of two retinoids on the induction of benzo[a]pyrene metabolizing enzymes by the more potent inductor 2,3,7,8-tetrachlorodibenzo-p-dioxine (TCDD) was investigated. The studies were performed with human diploid fibroblasts in culture. Vitamin A palmitate and all trans-retinoic-acid were found to prevent the TCDD induced increase of benzo[a]pyrene metabolism in a dose-dependent manner. The fact that this effect was immediately reversible makes it unlikely that it was due to non-specific toxic effects. The data suggest that retinoids cause a preferential inhibition of the de novo synthesis of benzo[a]pyrene metabolizing enzymes. PMID- 11219863 TI - The influence of occupation on health--some results from a study in the UK oil industry. AB - This study describes the patterns of mortality of 35,000 male employees, with a minimum of 1 year's continuous service, who worked at 8 refineries in the UK in the period 1.1.50-31.10.75. The trace rate of those involved was 99.8%. Overall the ratio of observed to expected deaths was 0.84 (O = 4406, E = 5259.9, P < 0.00001). The numbers of deaths for many of the chronic degenerative diseases were lower than 'expected'. The number of observed deaths from all cancers was appreciably less than expected (O = 1147, E = 1286.4, O/E = 0.89, P = 0.00006). Lung cancer was particularly reduced (O = 416, E = 532.7, O/E = 0.78, P < 0.00001); there was no excess of leukaemia (in workers including some exposed to benzene). Other comparable studies have suggested an excess of gastrointestinal cancer. In the present study deaths from oesophageal, stomach, intestinal and rectal cancer were slightly raised for all workers (O = 346, E = 328.6, O/E = 1.05, P < 0.4); this was particularly noticeable for those joining before 1950 with long service and with increased latent interval. There were also excesses based on small numbers of deaths from nasal cancer (O = 7, E = 3.1, O/E = 2.24, P < 0.05), and melanoma (O = 14, E = 6.5, O/E = 2.16, P 0.01). PMID- 11219864 TI - Studies on a new case of xeroderma pigmentosum (XP3BR) from complementation group G with cellular sensitivity to ionizing radiation. AB - XP3BR is a fibroblast strain derived from a xeroderma pigmentosum patient exhibiting severe mental retardation in addition to the typical changes in the skin. No tumours have been observed by 6 years of age. Cells from this patient had no detectable excision repair of u.v. damage. The defect in daughter strand repair was also characteristic of excision-defective XP's. The material was assigned to complementation group G and is the second (unrelated) example from this group. XP3BR cells were more sensitive than normal cells to the lethal action not only of u.v. but also of gamma irradiation, in contrast to all other XP cells tested to date including XP2BI, the other representative of complementation group G. The u.v. sensitivity was similar to that of strains from complementation groups A and D, confirming the correlation between extreme u.v. sensitivity and the presence of neurological defects. Following treatment with u.v., XP3BR, and other XPs gave more 6-thioguanine resistant mutants than normal cells whether the comparison was made per unit of dose or per lethal event. After low doses of gamma irradiation XP3BR cells were more mutable than normal or XP2BI cells. PMID- 11219865 TI - Carcinogenicity of the isomeric, N-nitroso-delta3-and N-nitroso-delta2 piperidines in rats and the in vivo isomerization of the delta3-to the delta2 isomer. AB - N-Nitroso-1,2,3,6-tetrahydropyridine (N-nitroso-delta3-piperidine), N-nitroso 1,2,3,4-tetrahydropyridine (N-nitroso-delta2-piperidine) and N-nitroso-3,4 epoxypiperidine were tested for carcinogenicity in Fischer 344 rats. The unsaturated nitrosamines were administered in drinking water (100 mg/l). The epoxide was administered by gavage in corn oil (11.5 mg/ml, 0.2 ml twice a week). Both of the unsaturated nitrosamines were potent carcinogens (most of the animals died by the 35th week), and both produced many esophageal tumors, a property which they have in common with the parent compound, N-nitrosopiperidine. The spectrum of the other tumors formed, however, was different. The delta3-isomer produced hemangioendothelial sarcomas in the liver, which were absent in the tumor spectrum of the delta2-isomer and N-nitrosopiperidine. The delta2-isomer, on the other hand, produced tumors of the forestomach and the oropharynx, which were essentially absent in the rats treated with the delta3-isomer. N-nitroso-3,4 epoxypiperidine was a toxic compound (8 deaths in the first 5 weeks), but most of the remaining animals survived to 40 weeks. Of these, 8 animals died of induced tumors (esophagus and liver). The delta2- and the delta3-isomers were administered by gavage to groups of rats and the blood of these animals was withdrawn at timed intervals. Analysis of the serum revealed that both of the nitrosamines were cleared rapidly from circulation but that at the same time the delta3-isomer was being isomerized to the delta2. The reverse transformation did not occur in vivo. PMID- 11219866 TI - Sister chromatid exchanges and chromosome aberrations in V79 cells induced by aflatoxin B1, B2, G1 and G2 with or without metabolic activation. AB - Cells from Chinese hamster cell line V79 were pulse treated for one hour with aflatoxin (AF) B1, B2, G1 and G2 at various doses with or without the metabolic activation system-S9 mix. With metabolic activation, all these toxins caused significant increases of frequencies of sister chromatid exchanges (SCE) in a dose-dependent manner. Based on the rate of SCE induction, the relative order of potency was established as AFB1 > G1 > G2 > B2. Without metabolic activation, all four toxins had no or very little effect over the same dose ranges used for SCE induction with activation. Induction of chromosome aberrations in V79 cells after a one hour pulse treatment with AFB1 and G1 plus S9 mix was also studied. A dose and time dependent increase of aberrations was observed for both compounds. AFB1 again is a more potent aberration inducer than AFG1. PMID- 11219867 TI - Polycyclic hydrocarbons induction of diphtheria toxin-resistant mutants in human cells. AB - Stable spontaneous mutants resistant to diphtheria toxin are present in the human cell line (EUE) at a frequency of 0-8 x 10(-6). Mutation increases by a number of polycyclic hydrocarbons have been used as an estimate of their carcinogenic potency. Eight polycyclic hydrocarbons of decreasing carcinogenic potency were assayed: 7,12-dimethylbenz[a]anthracene, 3-methylcholanthrene, benzo[a]pyrene, benz[a]anthracene, dibenz[a,c]anthracene, dibenz[a,h]anthracene, chrysene, anthracene, and a well known mutagenic substance, ethyl methanesulfonate. In our system, which does not require an exogenous source for metabolic activation, the most potent hydrocarbons, 7,12-dimethylbenz[a]anthracene, 3-methylcholanthrene and benzo[a]pyrene revealed a strong mutagenic effect, whereas three non carcinogenic hydrocarbons, anthracene, benz[a]anthracene and chrysene were not mutagenic. Our results indicate that there is a relationship between mutagenesis and carcinogenic potency for the tested polycyclic hydrocarbons. The maximum recovery of diphtheria toxin mutants was observed after an expression time of three weeks, corresponding to 10 cell generations. PMID- 11219868 TI - Repair of ethylnitrosourea-induced DNA damage in the newborn rat. I. Alkali labile lesions and in situ breaks. AB - The extreme sensitivity of the developing rat brain to tumor induction by N-ethyl N-nitrosourea (ENU) has been ascribed to the relatively inefficient repair of the presumed promutagenic lesion O6-ethylguanine from brain DNA. We have compared the brain of the newborn rat with liver, kidney and lung with respect to the repair of other types of DNA lesions that ENU induces, namely single strand breaks and alkali-labile lesions. The induction and repair or loss of these lesions has been analysed by alkaline sucrose gradient sedimentation using both mild as well as strong alkaline hydrolysis conditions. We found that ENU induces few lesions in the DNA of various organs that are detectable as breaks after mild alkaline hydrolysis. 24 h after ENU treatment such lesions are no longer detectable in brain DNA, while they are detectable in the DNA from other organs up to 10 days after ENU treatment. The number of ENU-induced lesions, detectable as breaks after strong alkaline hydrolysis, is far larger. These lesions were persistent in kidney DNA, disappeared slowly from liver DNA (t(1/2) = about 10 days), and more rapidly from brain and lung DNA (t(1/2) = 2-3 days). The latter result seems to be in contradiction with various reports that a large fraction of the ENU-induced alkali-labile lesions are stable in vivo. This difference between our results and those of others might be due to a difference between proliferating and non proliferating cells. Whether the alkali-labile lesions are removed from brain and lung DNA by a specific repair mechanism or by other causes remains to be investigated. PMID- 11219869 TI - Induction of sister chromatid exchanges by carcinogens mediated through cultured rat liver epithelial cells. AB - A cloned, untransformed rat liver cell-line, LNRL (with the normal diploid karyotype and epithelial morphology) was tested for use as the metabolizing component in a co-cultivation system for carcinogen-screening using sister chromatid exchanges (SCE) as the criterion. The well characterized early cultures of LNRL cells were co-cultivated with Chinese hamster ovary (CHO) cells, the target commonly used for the induction of SCE, and exposed to different concentrations of various chemicals for 24 h. Two polycyclic hydrocarbons, 7,12 dimethylbenz[a]anthracene and benzo[a]pyrene did not produce any SCE in CHO cells cultured alone, but produced a significant number of SCE in CHO co-cultivated with LNRL. The aromatic amine, 2-acetylaminofluorene, and the potent carcinogenic mycotoxin, aflatoxin B1, induced SCE to a limited extent even in CHO cells cultivated alone, but in the presence of liver cells the SCE frequency was greatly increased. Aflatoxin G2, the least potent of the aflatoxins, also produced a response in the co-cultivation system. These results indicate that cultured liver cells can be used as the metabolizing cells in co-cultivation systems for carcinogen-screening. The advantages of this assay over those employing liver microsomal fractions are discussed. PMID- 11219870 TI - A high pressure liquid chromatography study on the removal of DNA-bound aflatoxin B1 in rat liver and in vitro. AB - Following intraperitoneal administration of [3H] aflatoxin B1 (AFB1) to young adult male rats, there is rapid uptake of the carcinogen by the liver, the target organ for carcinogenesis, leading to DNA covalent binding. Acid hydrolysis of this DNA shows that after 2h, the major DNA adduct is trans 8,9-dihydro-8-(7 guanyl)-9-hydroxy AFB1 (AFB1-gua). By 24h after AFB1 administration the major DNA adduct is no longer AFB1-gua but a product with the identical retention time on h.p.l.c. to 8,9-dihydro-8-(N5-formyl-2',5',6' triamino-4' oxo-N5-pyrimidyl)-9 hydroxy AFB1 (AFB1-triamino-Py). 48h after carcinogen administration, only a small amount of AFB1-gua remains and the major product is AFB1-triamino-Py. The half-life of removal of AFB1-gua is 22h, while AFB1-triamino-Py is much more persistent. In vitro incubation studies on DNA isolated from rats treated 2h previously with [3H] AFB1 show that at pH 7.4 AFB1-gua is the major product released from the DNA with some release of 8,9-dihydro-8,9-dihydroxy AFB1, (AFB1 diol). If more extensively reacted AFB1-DNA is used than that obtained from in vivo administration, then the rate of AFB1-diol release is enhanced while that of AFB1-gua is reduced. It would appear, therefore, that much of the release of AFB1 from DNA in vivo within the first 24h is probably not through a DNA repair process but through chemical release arising from the positively charged N7 guanine. There is considerable conversion of AFB1-gua to AFB1-triamino-Py on in vitro incubation of DNA as well as AFB1-gua and AFB1-diol release. By 24h approximately 66% of the bound AFB1 is in the form of AFB1-triamino-Py and after 48h the conversion is complete. The complex pattern of AFB1-release from DNA may have important consequences in both the induction of mutations and in tumour initiation. PMID- 11219871 TI - Evidence for the involvement of lesions other than O6-alkylguanine in mammalian cell mutagenesis. AB - Marked differences between the mutagenic efficiency of N-methyl-N-nitrosourea (MNU), a potent carcinogen, methyl methane sulphonate (MMS) and dimethyl sulphate (DMS), both weak carcinogens, have been reported at the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and ouabain loci in V79 cells. Differences in levels of O6-guanine methylation produced by these alkylating agents, has been interpreted as indicating that O6-methylguanine is the DNA lesion specifically responsible for their mutagenic and carcinogenic effects. Because of the heterogeneity of molecular events which can result in forward mutation this conclusion seems unjustified. The development and characterisation of a reverse assay from 6-thioguanine resistance and HAT medium sensitivity (TG(R) and HAT(S)), to 6-thioguanine sensitivity and HAT medium resistance (TG(S) and HAT(R)) HGPRT(-)-->HGPRT+ in V79 cells, has allowed us to test the above hypothesis in a more specific way. Ethyl methane sulphonate, a weak carcinogen and MNU, both of which produce significant levels of O atom alkylation, were similarly effective mutagens in the reverse direction. At equitoxic doses, DMS was 40-60 fold less efficient. There was however, no quantitative correlation between numbers of revertants induced and measured levels of O6-alkylguanine. From these and other observations it is concluded that O6-alkylguanine is not the only potentially mutagenic lesion in mammalian cells. PMID- 11219872 TI - Comparative activity of 4,4'-diaminobiphenyl (benzidine) and its terphenyl analogue, 4,4'-diaminoterphenyl, in two in vitro assays for potential carcinogenicity. AB - The carcinogen 4,4'-diaminobiphenyl (benzidine) has been compared in vitro with its terphenyl analogue 4,4''-diaminoterphenyl using the Salmonella reverse mutation assay and the BHK cell-transformation assay. The responses observed, taken together with a consideration of chemical structures, indicate that the terphenyl compound is a potential carcinogen. These findings may contribute to an understanding of the mechanism of action of benzidine as a carcinogen. PMID- 11219873 TI - Metabolism of the bay-region trans-1,2-dihydrodiol of benz[a]anthracene in rat liver microsomes occurs primarily at the 3,4-double bond. AB - The bay-region hydroxyl groups of benz[a]anthracene (+/-)trans-1,2-dihydrodiol are known to be exclusively in quasi-axial conformations. This dihydrodiol was stereoselectively metabolized in rat liver microsomes to form two optically active 1,2,3,4-tetrahydrotetrols as the predominant products. Thus, the bay region axial hydroxyl groups of benz[a]anthracene trans-1,2-dihydrodiol do not direct metabolism away from the vicinal 3,4-double bond. PMID- 11219874 TI - Evidence-based clinical guidelines for palliative care: the work of the APM Science Committee. PMID- 11219875 TI - Using bisphosphonates to control the pain of bone metastases: evidence-based guidelines for palliative care. AB - This work was undertaken by the Science Committee of the Association for Palliative Medicine of Great Britain and Ireland (APM) as a demonstration project in developing clinical guidelines relevant to palliative care from a pragmatic approach to literature review and grading of clinical evidence. CANCERLIT and Embase were searched for relevant papers written in English, published since 1980. Each study identified was rated against agreed criteria for levels of evidence. Most studies were not specifically designed to define speed of response, and were not undertaken in palliative care patients. Thus, careful reading and grading of each study was necessary. Sufficient evidence was identified to make recommendations for clinical practice in a palliative care population of patients, and areas for future research have been identified. Bisphosphonates appear to have a role in managing pain from metastases which has been refractory to conventional analgesic management and where oncological or orthopaedic intervention is delayed or inappropriate. PMID- 11219876 TI - Identifying attitudinal barriers to family management of cancer pain in palliative care in Taiwan. AB - The purpose of this study was threefold: (1) to examine attitudes held by Taiwanese family caregivers of hospice inpatients with cancer that serve as barriers to cancer pain management; (2) to determine the relationship of attitudinal barriers to family caregiver hesitancy to report pain and to administer analgesics; and (3) to determine the relationship of attitudinal barriers to the adequacy of analgesics used by the patient. A total of 80 pairs of palliative care inpatients and their primary family caregivers participated in this study. Family caregivers completed the Barriers Questionnaire-Taiwan (BQT) form and a demographic questionnaire. The instruments completed by patients consisted of the Brief Pain Inventory-Chinese version and a demographic questionnaire. The data revealed that Taiwanese family caregivers of palliative care patients with advanced cancer had concerns about reporting pain and administering analgesics, particularly as they related to disease progression, side-effects and p.r.n. analgesics. Older and less-educated family caregivers scored significantly higher on the BQT than did their younger, more educated counterparts. Family caregivers' concerns measured by the BQT were related to family caregivers' reluctance to administer analgesics to their patients. Implications for a broader understanding of analgesics in the advancement of pain management in palliative care in Taiwan are discussed. PMID- 11219877 TI - Nonwhite ethnicity and the provision of specialist palliative care services: factors affecting doctors' referral patterns. AB - The aim of this paper was to examine the use of palliative care services by members of black/minority ethnic communities. Referral patterns of hospital consultants and general practitioners (GPs) to Birmingham St Mary's Hospice were examined. Semistructured interviews were carried out to explore doctors' perceptions of the benefits and limitations of hospice services for their black/minority ethnic patients and to identify potential barriers to referral. In total, 27 doctors were interviewed: 15 hospital consultants and 12 GP. The GPs were selected according to size of practice within areas of Birmingham with significant black/minority ethnic populations. Referrals received by the hospice for the period April 1996 to November 1997 were collected from the Hospice's computerized database. Results show that, compared to white Europeans, there was an underutilization of day care and inpatient hospice services by members of black/minority ethnic communities. Doctors did, however, refer their black/minority ethnic patients for hospice home-care services: 8.5% of referrals received by the hospice were for nonwhite patients. This referral rate increased to 19.3% in specific postcode areas known to have significant black/minority ethnic communities. Further research is needed to establish levels of awareness, explore attitudes towards palliative care services and assess the demand for specific services within various black/minority ethnic communities. PMID- 11219878 TI - Common threads? Palliative care service developments in seven European countries. AB - Since the late 1960s hospice and palliative care services have been developing in many European countries. Although attention has been given to patterns of development in specific national contexts, so far we lack a comparative understanding of how these services are organized and delivered. Such a comparison poses certain practical and methodological difficulties. It does, however, allow a wider view of the current provision of palliative care in Europe, together with a consideration of implications for the future. We report on an analysis of palliative care developments in seven European countries which gave attention to early origins, patterns of provision, and structural and policy integration. We conclude that, despite different processes of development, the emergent discipline of palliative care now finds its most congenial home within the structures of the formal health care system. Accordingly, inequities between the seven countries can be more clearly identified, posing continuing challenges to policy makers and planners who operate with a European perspective. PMID- 11219879 TI - Dimensions of the role of the social worker in palliative care. AB - There has been very little research focusing on the role of the social worker in a specialist palliative care service. A qualitative research methodology was used which sought to capture the essence of that role, as perceived by those carrying it out, rather than simply to approach it as a series of tasks. A specialist palliative care social worker was asked to describe her role in selected cases that she had worked with. The interviews were taped and transcribed. The data were then analysed for themes using the techniques of constant comparative analysis. The themes were grouped into six categories and a conceptual framework developed. This was then validated with four other experienced social workers. Integrating categories in the framework were knowing and working with limits and values and valuing. The four other categories, a family focus, being a team member, managing the environment and managing anxiety related to the everyday activities of the social worker. The results are discussed in relation to social work in other specialties and in relation to other professional roles in specialist palliative care. Further research is needed to add the perspective of the social worker's client to understanding of the role. PMID- 11219881 TI - Inter-rater reliability of formally trained and self-trained raters using the Edmonton Functional Assessment Tool. AB - The primary objective of this study was to determine the inter-rater reliability of the revised version of the Edmonton Functional Assessment Tool (EFAT-2). A second objective was to determine whether both formally trained and self-trained therapists had an acceptable level of inter-rater reliability. The EFAT-2 was administered to consenting palliative care patients by one of two independent physical therapist rater pairs; one pair self-trained (R1, R2) and the other formally trained (R3, R4). The intraclass correlation [ICC (1,1)] for R1, R2 was 0.97 [95% confidence interval (CI) 0.94-0.99] and for R3, R4 was 0.95 (95% CI 0.90-0.98). The standard error of measurement was 1.09 and 1.44, respectively. The Kappa statistic for the rater pairs on individual EFAT items ranged from 0.17 to 0.96. The results suggest that both formally trained and self-trained therapists obtain an acceptable level of inter-rater reliability when using the EFAT-2. PMID- 11219880 TI - Death anxiety in brain tumour patients and their spouses. AB - When a person is diagnosed with a severe disease, it seems plausible that existential questions and death anxiety are easily intensified. The aims of this study were to explore whether this is the case, to what extent patients and their next of kin experience death anxiety, and how these experiences are expressed. Following a purposive sampling technique, 20 patients with brain tumours and 15 of their next of kin took part in interviews. A content and context analysis were performed using a hermeneutic approach, in order to identify and analyse main categories. Six main categories common to patients and their next of kin emerged during the process: (1) emotional reactions that could be related to death anxiety and included general anxiety, anguish, sadness, hope and despair; (2) existential fear, existential anxiety and existential pain; (3) contradictions; (4) trigger situations; (5) coping strategies related to death anxiety; and (6) new values for life. Besides these categories, a further category emerged, experiences characteristic of the next of kin. The study shows that both the patients and their next of kin are preoccupied with existential thoughts and death anxiety. The problems are easily overlooked as the death anxiety is not always expressed directly. Staff need to be more aware of these situations in order to provide existential support. PMID- 11219882 TI - Using videoconferencing in palliative care. AB - Recent technological advances and reducing costs have meant that videoconferencing is a possible new medium for health-care teams. The IMPaCT (Interactive Multimedia Palliative Care Training) project began in 1997 with the aims of assessing the practicalities of videoconferencing in palliative care and assessing its educational effectiveness. The use of videoconferencing was closely evaluated during the first 2 years of the project and this paper presents the results of that monitoring. Twenty-two sites were linked worldwide, reaching 136 professionals without the costs or time needed to travel. The savings on travel and time within the UK alone would have paid for the equipment in 1 year. Sites only continued with videoconferencing if they reached a point where their organization saw the advantages of videoconferencing. Links were easy to establish and rarely failed regardless of distance. Users rapidly adapted to the new medium, and links could be used in a variety of settings and audiences, including journal clubs and expert workshops. Videoconferencing offers a new and unique way of supporting palliative care professionals while reducing time and costs for both tutors and learners. PMID- 11219883 TI - The use of pilocarpine in opioid-induced xerostomia. PMID- 11219884 TI - Met and unmet needs in hospital-based home care: qualitative evaluation through open-ended questions. PMID- 11219885 TI - Teaching palliative care in east Asia. PMID- 11219886 TI - The effects of patients' and practitioners' preferences on randomized clinical trials. PMID- 11219887 TI - Palliative medicine undergraduate education detailed in university prospectuses and websites. PMID- 11219889 TI - Pets and animal-assisted therapy. PMID- 11219888 TI - The importance of low magnesium in palliative care. PMID- 11219890 TI - Challenges of decision making for families of children with single or multiple chronic conditions. AB - When a child is diagnosed with a chronic illness, families begin a constant cycle of decision making. Many of these decisions surround health care treatment. These families can be divided into two groups: those with children newly diagnosed with a chronic condition and those with children who have a preexisting illness. If a new diagnosis represents a family's entrance into the medical community, the decision-making process can be confusing and difficult. For the family of a child with a preexisting condition, making repeated decisions about treatments can be additionally stressful and anxiety provoking because of their medical history. How do families with a child with a preexisting medical condition differ in their decision making? What factors affect their decisions? The nurse practitioner has a critical role interacting with both types of families and guiding the decision making process. Therefore, understanding the family and their previous experience is crucial to determine how nurse practitioners can best tailor interventions to promote effective decision making. PMID- 11219891 TI - Assessing parental concerns of children with diabetes. AB - This study assesses levels of parental concern in a group of families who had a young child diagnosed with type 1 diabetes. Despite high levels of concern for hypoglycemia and hyperglycemia, the parents reported that they managed their child's diabetes as recommended by the health care providers. No correlation was found between the concern ratings and level of glycemic control or incidence of severe hypoglycemic events. PMID- 11219892 TI - Children with chronic conditions: the importance of growth assessment. AB - Growth assessment is crucial in the evaluation of all children. The growth of children with chronic conditions is often inadequately assessed by subspecialty services because of the following beliefs: (1) short stature is secondary to the disorder and therefore the cause is known, (2) poor growth is caused by a syndrome and is untreatable, and (3) growth is assessed adequately by the children's primary care providers. In reality, growth failure in children with chronic conditions may be caused by other factors and may be treatable. In addition, growth is often inadequately assessed by primary health care providers. Growth abnormalities should never be ignored or minimized in populations of children having other significant health care problems. PMID- 11219893 TI - Nurse practitioner intervention to improve the use of metered-dose inhalers by children with asthma. AB - Metered-dose inhalers (MDIs) have become a mainstay of maintenance therapy for various allergic and respiratory conditions. When used correctly, MDIs are as effective as nebulized medications. Patients use MDIs incorrectly in many cases because of poor instruction and lack of spacer devices. Nurses and physicians often teach the technique improperly. Nurse practitioners can have a positive impact in improving care through better patient and staff teaching and the use of spacer devices with MDIs. PMID- 11219894 TI - A school-based asthma clinic: a partnership model for managing childhood asthma. AB - Childhood asthma is a major public health problem. It is the leading cause of childhood hospitalizations and school absences despite recent advances in management. Current standards of care call for client education as partners in disease management. In pediatrics, this calls for shared decision making between health care provider, parent, and child. Traditional care delivery systems often fall short of meeting this standard. This article describes a nurse practitioner run school-based asthma clinic, designed as a pilot study, to fill these gaps. Characteristics of the community that affected outcomes are described. PMID- 11219895 TI - Perinatally acquired human immunodeficiency virus infection in infants: updated guidelines for prevention, diagnosis, and initiation of treatment. AB - Perinatally acquired human immunodeficiency virus (HIV) infection can be prevented through education and, for women with HIV and their babies, administration of chemoprophylaxis during the perinatal period. When perinatally acquired HIV infection occurs, early intervention can promote the quality and duration of the infant's life. This report updates and consolidates current recommendations related to the prevention of perinatally acquired HIV infection, as well as recommendations for the management of perinatally exposed and infected infants through the first year of life. PMID- 11219896 TI - Reporting medical neglect effectively: a guide for nurse practitioners working with child protective services. AB - Health care providers who suspect or observe medical neglect of chronic health problems in children are obligated to report the findings to Child Protective Services (CPS). Such reporting results in uneasiness for clinicians, who may jeopardize their therapeutic relationships with the patient and family, or worse, provoke them to withdraw from treatment. To the contrary, reporting medical neglect and discussing it openly and empathetically with the family can foster more cohesive teamwork and prompt families to address their problems. Knowing your state's child abuse laws, how to effectively report medical neglect, and how to communicate and collaborate with CPS caseworkers may result in the provision of therapeutic services to families. Enhancing family functioning can result in increased efforts toward caring for their child's medical problem. PMID- 11219897 TI - Discontinuing treatment in children with chronic, critical illnesses. AB - Decisions about optimal treatment for critically ill children are qualitatively different from those related to adults. Technological advances over the past several decades have resulted in myriad treatment options that leave many children chronically, critically ill. These children are often technology dependent. With new technologies and new patient populations comes the responsibility to understand how, when, and why these technologies are applied and when technology should not be used or should be withdrawn. Much has been written about ethical decision making in the care of chronically, critically ill adults and newborns. In this article, relevant factors about the care of children older than neonates are described: standards, decision makers, age of the child, and pain management. A case study is used as a mechanism to explore these issues. Dimensions of futility, discontinuing aggressive treatment, and a consideration of benefits and burdens are integrated throughout the discussion to inform nurse practitioner practice. PMID- 11219898 TI - Home care considerations for chronic and vulnerable populations. AB - Conducting a predischarge home assessment can provide important information to the hospital care team for discharge planning and postdischarge care. In addition, a predischarge home visit assists the family in preparing for the infant or child's care needs. This report describes an Environmental Assessment Guide initially developed and subsequently used in two nursing research studies. Anecdotal information from advanced practice nurse care records is provided to illustrate issues relating to predischarge assessment. PMID- 11219899 TI - [Hemorrhagic and hypoxic-ischemic brain lesions in premature infants on artificial ventilation]. AB - Major intraventricular hemorrhage (IVH) and cystic leucomalacia (PVL) are major causes of mortality and neurologic morbidity in premature infants that are strongly associated with long-term neurodevelopmental sequelae. Preterm babies ventilated by intermittent positive pressure ventilation are in higher risk for this type of lesion. We studied incidence of major intraventricular bleeding (with ventricular dilatation and parenchymal involvement) and cystic periventricular leucomalacia in 79 preterm babies who required mechanical ventilation for respiratory-distress syndrome (RDS), admitted on Department of Neonatology of the Pediatric University Hospital in Sarajevo from February 1999. to May 2000. Thirty-five babies were classified as less than 32 weeks of gestation. Major intraventricular hemorrhage and cystic leucomalacia were documented in 5 babies (10.2%) of 49 survivors. Two babies developed posthemmoragic hydrocephalus and required shunting. Severe brain damage was more common in ventilated infants with gestational age with (32 weeks of gestation (23.5%) compared with the babies > 32 weeks of gestation (2.9%). The severity of RDS also correlated with an increased risk of severe IVH. PMID- 11219900 TI - [Incidence of respiratory distress syndrome in premature twins]. AB - Respiratory distress syndrome (RDS) is a syndrome of respiratory malfunction occurring in pre-term newborns. Twin pregnancy is a risk factor for the occurrence of RDS. The objective of our study is to analyse RDS incidence in pre term twins and to determine the mortality in this group of newborns compared to single pregnancy pre-term babies. The study is based on the data collected in Clinic for Gynaecology and Obstetrics, Neonatology Department in the year 1999. RDS was diagnosed on the basis of clinical status and radiology findings. In the course of the test period, 544 pre-terms were born, 91 (16.7%) of them being from twin pregnancies. RDS developed in 132 newborns from single pregnancies (29.1%), in 28 newborns from twin pregnancies with RDS developed in both twins (30.7%) and in 19 babies whose twin siblings did not have RDS. If we consider gestation age, RDS developed in 28.6% twins born between 32nd and 36th gestation week and in 20.45% single newborns of the same age. The results were similar in younger gestation age. Mortality rate in the tested group was 17.8% and 9% in the control group. These results lead us to the conclusion that pre-term newborns from twin pregnancies tend to develop RDS, a more difficult clinical status, have more complications and higher mortality rate than the newborns from single pregnancies. PMID- 11219901 TI - [Pulmonary complications during mechanical ventilation in the neonatal period]. AB - The pulmonary complications (PC) during mechanical ventilation were caused by barotrauma, infection, oxygen toxicity and excessive pulmonary extravascular fluid. The most frequent manifestations are: pneumothorax, pulmonary haemorrhage and lobar or segmental athelectasis. This is a retrospective study conducted between 1.1.1990 till 31.8.2000. The aim of this study was to evaluate the frequency of the pulmonary complications during mechanical ventilation in 163 ventilated neonates, as well as the relation towards gestational age, birth weight, primary disease and the outcome. The most common causes for mechanical ventilation were: hyaline membrane disease in 95 (58.3%) preterm babies, perinatal asphyxia in 26 (16%) and less frequent conditions such as: apnea, congenital heart diseases, neonatal infections and surgical cases. 25/163 (15.3%) ventilated pts have developed pneumothorax, 29 (17.7%) athelectasis and 14 (8.5%) pts had pulmonarly haemorrhage. The pulmonary complications were more frequent in preterm newborns with significant influence at the duration of the ventilation and the outcome. However, pulmonary complications could not be completely avoid, so we would like to underline the importance of preventive measures with the aim of decreasing PC incidence. PMID- 11219902 TI - [TORCH infections in mothers as a cause of neonatal morbidity]. AB - When possible, diseases by expectant mothers and newborns, like long-term disabilities also, should be prevented by establishing early diagnoses, evaluation and implementation adequate therapy. The major goal of medical care is prevention of disorders with provision of adequate prenatal care for the expectant mother and precautions regarding the exposure to teratogenic infections. The range of pathological conditions produced by infections agents is wide, and the difference between maternal and fetal effects caused by any one agent is also important. Some maternal infections, especially during the early gestation, can result in fetal loss or malformation because the ability of the fetus to resist infectious organisms is limited and the fetal immunologic system is unable to prevent the disemination of infectious organisms to the various tissues. These infections are responsible for significant congenital neonatal morbidity as for as compromises a child's quality of life and infertility and sterility. One group of microbial agents--generally known as TORCH infections can cause remarkably similar manifestations, and is uncommon to test all when a prenatal infection is suspected. We analysed the practice of TORCH analyses with our patients and their mothers during last year (1999th) at the Pediatric Clinic and Clinic of Gynecology and Obstetrition-UCC Tuzla. At this time there were 5.028 deliveries. Out of short figure 544 or 10.8% newborns were early born and 245 or 4.8% were hypotrophic and 62 were still-born or 12.3 from 1000 deliveries. TORCH infection was analysed only in few cases. In the same period there were 3.457 children treated at the Pediatric Clinic in Tuzla. Only in 20 cases or 0.58% TORCH was made. Three or 15% were with remarkable sequeles like microcephaly, cerebrospinal liquid abnormality, seizures, hepatomegaly, cirrosis etc. TORCH analysis was made with all mothers. Only one was serologic CMV positive and we started with the therapy. History of four mothers or 20% have data about spontaneous abortions, and in other four or 20% we found data about early deliveries. The prevention of conatal infections was not made by any one. In our small group we made TORCH because of evident problems that were suspected of conatal infections. We concluded that there is a big risk of untreated maternal infections with women in fertile age in Bosnia and Herzegovina. This problem is not enough present in our medical practice. PMID- 11219903 TI - [Convulsions in the early neonatal period]. AB - Convulsions are relatively frequent in neonatal population. They are also the most dramatic sign of a disorder of the central nervous system. Clinical signs of convulsive seizures in neonatal period differ greatly from those occurring in a later stage. Our study involves a five year period, in the course of which we analysed all newborns with convulsions occurring in the early neonatal period. The objective of the study was to determine the incidence, aetiology and time of occurrence of convulsions, to determine the mortality rate in this group of newborns and to assess risk factors for the development of convulsions. In 29.423 newborns tested in the course of the study at our Clinic, convulsions were found in 38 (0.13%) of them. Regarding the gestation age, 68.4% of the cases of convulsion occurred in at term newborns. The most frequent aetiology factor was a perinatal damage, in 60.4%, and the majority of convulsive seizures occurred in the period between the 2nd and 7th day (84.3%). Five of the tested newborns died (13.5%), three of them having suffered from convulsions in the first 24 hours. The authors came to the conclusion that many factors influence the development of convulsions, and that the occurrence of convulsions in the first 24 hours and heavy perinatal brain damage give bad prognostics for survival. PMID- 11219904 TI - [Use of prostaglandins in neonatal cardiology]. AB - The current trend in neonatal cardiology assumes the administration of prostaglandins. Prostaglandins are indicated as a palliative and not definitive therapeutic medicament in neonates with duct dependent congenital heart anomalies. The aim of this study is to evaluate the medicament Prostaglandin, first time administrated to neonatal cardiac patients, in Bosnia and Hercegovina. During December 1997 till June 2000. at the Neonatal department of Pediatric Clinic in Sarajevo 1162 pts were admitted, of which 17 (1.4%) with congenital heart disease have received prostaglandin therapy, with the mean age of 4.5 days (45 minutes till 20 days). 13/17 (76.5%) pts were boys and 4/17 (23.5%) girls, with mean body weight of 3.125 gr (range: 1.250 g to 4.100 g), mean gestational age 40 weeks (range 34 to 42). The patients were admitted for: cyanosis, breathing difficulties or fatigue. Central cyanosis was evident at admission in 15/17 pts, whose oxygen saturation at admission was from 21% up to 76%. The diagnosis of congenital cyanotic heart anomalies was made in 15/17 pts (88%) by clinical examination, X ray, ECG and ultrasound examination and acyanotic duct dependent on 2/17 (12%) pts. The administration of prostaglandin's was necessary and of vital importance for life maintenance of these pts till the surgical correction of these congenital heart anomalies. Prostaglandin E1 (PGE1) was administrated by infusion pump with the mean doses of maintenance: 0.023 mcg/kg/min in 11/17 (65%), and Prostaglandin E2 PGE2 in 6 (35%) pts, maintenance doses of 0.38 mcg/kg/hour. The duration of the prostaglandin application was from 7 hrs up to 30 days, mean 12 days. Five (29.5%) pts were intubatued during the application of this medicament. The side effects of this therapy were present in 13 pts (76.4%): hyperpyrexis in 8, apnea in 2 and apnea + hyperpyrexis in 3 pts. 8/17 (47%) pts were operated and corrected abroad, they are now in good condition, and 9/17 (53%) pts died. The death causes were a part of complex congenital heart disease: impossibility of performing the heart surgery in the country when needed, impossibility of pts evacuation to the foreign cardiosurgical center on time, sepsis or persistent pulmonary hypertension. CONCLUSION: In pts with congenital heart disease whose survival is duct dependent, the availability is compulsory and the application of prostaglandins as a palliative medicament. The prostaglandins have made a revolution in saving children's lives in neonatal cardiology. PMID- 11219905 TI - [Obstetrical injuries of the brachial plexus]. AB - Although birth-related brachial plexus injury (BPI) was first described more than two centuries ago, it still represents therapeutic dillemma. Incidence is 0.37 2.0 per 1000 live births. The most frequent etiologic cause is extreme lateral traction and excessive fundal pressure in a case of shoulder dystocia. However, in last decade there are reports that cite of BPIs occurring prior to delivery in up to 46% cases--intrauterine maladaptation. In 1998. and 1999. at the Rehabilitation Department of Pediatric Hospital, Clinical University Center in Sarajevo 32 children with BPI were treated. The incidence is 2.67 per 1000 live births. There were 21 cases of Erb's palsy (65.63%), 2 cases of Klumpke's palsy (6.25%). Total plexus palsy was present in 9 children (28.63%), and Horner's Syndrome in 1 case. In 25.77% of cases (8 children) there was-no evidence of shoulder dystocia at delivery. Treatment of the brachial plexus injuries in newborn is still controversial. Proper immobilization in first 7-15 days is of great importance. In this study 25 children (78.13%), in average age of 4.6 days, were brought for examination with improper immobilization. The role of widely applied electrotherapy is controversial. Complete recovery is expected in about one half, and in this study it was achieved in 75% of cases (24 children). Consensus about timing od surgical approach does not exist still. However, there is strong agreement that decision about eventual surgical treatment should be based on clinical motor testing and that MRI should precede the surgery. Although the electrodiagnostic studies have proven to be of limited prognostic value in the evaluation of children with acute obstetrical brachial plexus injuries, electromyography should be performed prior the surgery in the aim of later comparison of the results. According to our data, at this particular moment in BiH surgical treatment in this age is not available, as well as use of MRI in diagnostics of BPIs. PMID- 11219906 TI - [Tetralogy of Fallot: postoperative monitoring of patients]. AB - In 25 patients, 13 boys and 12 girls, median age 5.5 years, in 1990-2000, surgical reparation of their heart defects were performed. Median age of diagnostic Tetralogy of Fallot was 3.2 months, range 1 day-2 years. Anoxic spells were present in three patients. Ten patients (median age 3 years, range 3 months 10 years) initially palliated with a modified Blalock-Taussig shunt, underwent a reparation at a median of 4.5 years after palliation. Median follow up was 4.2 years, range 3 months-10 years. The 30-day mortality rate was 16%. Mean right ventricular outflow tract gradient on echocardiography was 20.20 +/- 4.78, and mean oxygen saturation was 96% +/- 1.3. Two patients had non significant residual ventricular septal defect with left to right shunt, 7 right ventricular enlargement and almost all mild pulmonary regurgitation. Also two patients had Blalock-Taussig shunt's thrombosis. Before surgical reparation, one boy showed pulmonary valve's endocarditis. Complete atrioventricular block has been developed on one girl. No patient required reintervention during follow up and there was no late mortality. Almost all of our patients were asymptomatic, had normal activity, regularly exercised and some of them participated in school sport programs. Complete correction of Tetralogy of Fallot showed good results with normal life expectancy for the patients. PMID- 11219907 TI - [Review of patients with congenital heart anomalies treated at the University Clinical Center in Sarajevo 1997-2000]. AB - During April 1997 to October 2000, 65 children (61.5% female and 38.5% male) have been operated at KCU Sarajevo at the Hospital for Cardiac surgery. Diagnostic procedures, preoperative and postoperative treatment have been carried out at Pediatric hospital, Clinical center University of Sarajevo. The average age of establishing the diagnosis was 20 months and 4.5 years was the average age of surgical treatment. The most frequent defects were: Atrial septal defect 27.69%, Tetralogy of Fallot 16.92%, Patent ductus arteriosus 16.92%, Coarctatation of the aorta 7.69%, combination of more simple defects 7.69%, Atrioventricular septal defects 6.15%, Ventricular septal defect 4.61%, Pulmonary stenosis 4.61%, Anomalous pulmonary venous connection 4.61% and the other complex defects 3.07%. Among all cases 10.76% were associated with some of the syndromes. In 86.13% of cases total correction have been performed and palliative in 13.84% of cases. Death rate was 10.76%, and postoperative complications 21.53%. Catheterizations was performed on 14 patients (21.53%), and three of them had therapeutic interventional cardiac catheterization (coil, umbrella, balloon dilatation). The average timing of: preoperative procedures was 3.5 days, postoperative following 7.5 days and intensive care 2.2 days. PMID- 11219909 TI - [Ictal automatisms during partial complex seizures in 36 children]. AB - Partial complex seizures are relatively frequent type of epileptic seizures. These attacks are having aura in 60% of cases, that can be vegetative, motor, sensor or psychological one. Important is aura in the form of uncinatus seizures (unpleasant odor), because we must exclude tumor of temporal region in these patients. Altered consciousness comes after aura, patient has opened eyes, face can be pale or red, and automatism appear, in the form of different movements. These automatisms are often considered insignificant by parents or eyewitnesses. There is often misdiagnosis of this type of seizures, because only about 20% of standard EEG recordings find specific epileptic grapho-elements. Therapy of these seizures is difficult, with the success in only 50% of cases. Ictal automatisms were tested in the group of 36 children with partial complex seizures aged 4 to 17 years. Duration of epilepsy was 1 to 5 years. All patients had proved diagnosis of partial complex seizures, clinically and on electroencephalography, CT scan and MRI in medically intractable seizures. Eleven patients were videotaped during the attack. All patients had questionnaire filled by parents, about automatisms. Thirty-four patients (94.4%) had ictal automatisms, and 2 with epileptic focus in frontal region did not. Some patients had different types of automatisms. Most frequent ones were mimicking (15.19%), sitting-standing up (10.76%), swinging (8.23%), swallowing (7.59%) etc. It can be concluded that automatisms are almost obligatory part of partial complex seizure, and their registration is essential for correct diagnosis and treatment of these seizures. PMID- 11219908 TI - [Prognosis in vesicoureteral reflux]. AB - OBJECTIVES: To emphasise the importance of early diagnosis of Vesicoureteric Reflux (VUR) in prevention of renal failure. METHODS: General testing of children was followed by micturating cystourethrography (MCGU) for those with the diagnosis of urinary-tract infection. In cases where high level of VUR was determined, satic nuclear medicine scanning was performed using an isotope labeled substance (e.g. DMSA). RESULTS: 31 nephrology department patients were followed: 29 girls, 2 boys ages 0-15. MCGU showed 33 kidneys with reflux. 13 of the patients had reflux in the first or second degree. 7 patients showed reflux of the 2-3 degree while 13 had a high degree of reflux. Among the children under 7 years of age, total of 16 kidneys, DMSA showed various degrees of damage to the paranhaim and the development of scars. CONCLUSION: After the VUR has been diagnosed, it is difficult to predict whether scarring will take place. The possibility of scarring is higher among younger children when appropriate therapeutic modalities are not identified. PMID- 11219910 TI - [Birth asphyxia as a cause of cerebral palsy]. AB - Birth asphyxia is O2i CO2 exchange disorder during the labour, with consequent hypoxia and ischemia. The term "asphyxia" has been used unprecisely quite often. The most frequently used criteria for birth asphyxia have been: fetal bradycardia, meconium stained amniotic fluid, fetal acido-base status with umbilical artery pH value below 7.10, low Apgar score and need for endotracheal intubation. The correct Apgar score quantification depends on the examiner. Fetal acido-base status measured in umbilical artery could be useful biochemical parameter of birth asphyxia. Only if the fetal oxygen supply during the labour is severe and long enough disturbed, the neurological abnormalities will develop later. Our study has enrolled 70 children with various degree of motor impairment, detected during neonatal period and/or infancy. They have been followed up till 24 months chronological age for term neonates and 24 months corrected age for prematures. 34 children out of them have developed clear clinical signs of cerebral palsy. Birth asphyxia as a possible cause of cerebral palsy has been documented in 10 cases, e.g. 29.4%. The criteria for birth asphyxia have been low Apgar score, meconium stained amniotic fluid and clinical signs of hypoxic-ischemic encephalopathy. Fetal blood gas and acido-base measurements obtained from umbilical artery at delivery have been an important parameter of intrapartal asphyxia. Those measurements should be introduced as a routine method in our practice, in the cases of fetal heart deceleration, to asses the extent of fetal acidosis. PMID- 11219911 TI - [Hypochromic anemia in children with affective breath-holding spells]. AB - Breath holding attacks are most common in children aged 6 months to 6 years, in 76% of cases between 6 and 18 months of age. Very often they are misinterpreted as tonic epileptic seizures. They are provoked by frustration, anger or sudden injury. Child starts to cry, then holds the breath at the end of expirium. After a few seconds it becomes cyanotic, and losses consciousness. It is usually floppy, but sometimes stiffness, and clonic seizures can be present, and child can be diagnosed as having epilepsy. The form in which child is pale is less frequent, and crying is usually brief or even absent in this type. Breath holding attacks usually do not last more then one to three minutes. Good heteroanamnesis is essential for diagnosis, revealing provoking factors for each attack. Interictal EEG registration is usually normal. Attacks often spontaneously cease after 5 or 6 years of age, and do not require any medical treatment. In more severe cases behavioral therapy has shown good results. It has been noticed that those children in adolescence have syncope more frequent then rest of population. Seventeen children (12 male and 5 female) were investigated at Pediatric Hospital in Sarajevo as breath holding attacks in period from June 1997 to June 2000. Age of patients was between 5 months and 5.5 years (median was 11 months). Hypochromic anemia was present in 12 patients (76%), with average hemoglobin value of 8.2 g/dl (5.9-11.0 g/dl). All children had normal EEG recording. Iron therapy gave positive response in 8 out of 9 patients that were followed (88.9%). Three patients had not come for follow up. It is concluded that hypochromic anemia is often a part of clinical presentation of breath holding attacks in children, and iron therapy can stop them. PMID- 11219912 TI - [Magnetic resonance and magnetic resonance angiography in the diagnosis of vascular anomalies in childhood]. AB - The aim of this study is to demonstrate the accuracy of MRI and MR angiography, using 3D and 2D TOF sequences to diagnose vascular malformation in children with non-traumatic intracranial hemorrhage (subarachnoid or intracerebral hemorrhage). PATIENTS AND METHODS: In two years period 7 children, 4 boys and 3 girls range age 8 to 14 years with non-traumatic intracranial hemorrhage were examined on 1.0 TMR unit, using T1,PD,T2 WI and 3D and 2D TOF MR angiography with MIP reconstruction. RESULTS: In the group of 7 children, 2 were with aneurysms, 2 with AV malformation, and 1 with cavernous angioma. The results of these were correlated with those of IA DSA. The results were in agreement regarding the presence, location and size of aneurysms, the presence, vasculation and drenage of AV malformation. CONCLUSION: MRI with MR angiography is rapid and non-invasive examination which can confirm the diagnosis of vascular anomalies in children and to follow them up. PMID- 11219913 TI - [Peripheral insertion of central catheters in the treatment of pediatric patients with leukemia]. AB - In this paper we analyzed group of patients with leukemias in which was implanted peripherally inserted central catheters (PICC), which is safe and permanent intravenous line necessary for treatment in these patients. MATERIAL AND METHODS: In the period from January 1999. to September 2000. at the Oncology Department on Pediatric Clinic in Sarajevo we placed PICC in 18 patients with leukemia. Catheters were introduced through vena cubitalis and EMLA was used like local anestetic, All these manipulations were done with respect to asepsa rules. Tip of the catheter had to be situated in vena cava superior and its right position was checked by ultrasound. Management of catheter included everydays heparinisation, according strictly ordered rules and respect asepsa rules. RESULTS: PICC was placed in 18 patients with average of 6.5 years. According sex there were 61.1% males, and 38.9% females. Average period of using catheter was 2.7 months. In 44.4% cases catheter was taken out after finished treatment, but in 22.2% cases we had mechanical complications (spontaneous breakage of catheter or stop in it). In 33.3% patients catheter is still in function. CONCLUSION: Using PICC in patients with leukemia made significantly easier their treatment regarding decreasing of their traumatisation, regarding simplier vein access and reduction of the infection. In our investigated group we had not infection what was very important fact for outcome of this serious disease. PMID- 11219914 TI - [Helicobacter pylori and gastroduodenal disease in our patients: 2-year experience]. AB - Primary gastritis, duodenitis, peptic ulcer of stomach and duodenum are no longer considered to be disorders of the balance of secretion of acid and immune responses of the gastric mucose but it is thought to be caused by Helicobacter pylori infection. One of the most important factor causign the malignant gastric diseases such as carcinoma and non-Hodgkins MALT Lymphoma is an early infection by this spiral gram-negative bacterium. We performed byopsi of the gastric mucose in 80 of our patients. Endoscopic and histological results showed that 74 patients had gastritis 6 others had normal results. The highest incidence of disease was found in children of 11 to 14 years of age because 67.4% were girls and 22.4% were boys of this age. Ethiological analysis of patients with gastritis showed that Helicobacter pylori was isolated in bioptic material of 46 patients while results of other 28 patients were negative. PMID- 11219915 TI - [Clinical assessment of occult infections in children]. AB - Children's occult infections are characterised presenting pathogenic bacteries in blood of children in age 3 to 36 months, but they are good general aspect and orderly immunologic status and they don't have signs of focal infection. Manifestation of occult infections determined: age of child, increasing bodies temperature, testsphysical observance and clinical-biochemistry tests. Prevalence of manifestation occult infections is 3-8%, but they manifest ni a form occult bacteremia, occult pneumonia nad occult urinary infection. Methodic, systematic admission and adequate clinical-biochemical monitoring, we minimise sequeles of occult infections. Risk of serious sequeles at occult infections is importantly decreasing by epidemiological changes that it rises by using vaccination against Haemophilus influenzae and Streptococcus pneumoniae is leading ethiological source. Many contraversal opinions are presented in glance of therapeutic strategy at children's occult infection. Future of solutions at many hesitations ni context diagnosis and therapy of occult infections is established in using recent detectional tests /pneumococcus PCR, plasmas tumor reaction, interleukin la/ and preventive intervetions activities /conjugated pneumococcus vaccination/. PMID- 11219916 TI - [High-frequency ventilation in neonates with pulmonary hemorrhage]. AB - The high-frequency ventilation (HFV) has been in use in the World since early 70s, on patient (RDS, MPH, PPHN, etc.) who did not respond well as it was expected, on conventional mechanical ventilation (IPPV/IMV). At our Clinic we started to use this type of ventilation two months ago, and throw this work it was presented our first experience. In case report was showed massive pulmonary hemorrhage (MPH) in premature newborn 30 GW, where we applied HFV. Immediately after the bird conventional mechanical ventilation has been applied with positive pressure (IPPV) and surfactant has been given because RDS. After the MPH appeared we successfully applied HFV. PMID- 11219917 TI - [Cat-scratch disease]. AB - We report a case of fourteen years old boy with cat scratch disease. He was treated at Pediatric Clinic in January and February 2000. Cat scratch disease is benign infectious chronic disease which appears in all ages. It begins after contact with cat and its scratch. Yearly incidence of this disease for whole population is 0.77-0.86/100.000. The cause is bacillus Bartonella which is also called genus Rochalimaea. It is Gram negative, mobile, aerobe bacillus with ten flagellas on one pole. Our patient was admitted at hospital because of high temperature, paleness, fatigue, bad appetite and pains in his joint. Ultrasound and magnet resonance scans of liver and spleen showed enlarged but regulary contured liver and two focal changes with diameter 16 mm, 12 mm and 7 mm in spleen. All those focal changes were described as abscesses. Diagnose was set up according increasing titre of IF-Bartonella hensalae IgG 1:256 (positive). This diagnostic test was performed at Institute for microbiology and Immunology at Medical Faculty in Ljubljana. Disease had long lasting course, and was cured by antibiotics without surgical intervention. PMID- 11219918 TI - [Hypoparathyroidism]. AB - Hypoparathyreoidism of different etiology is the most common disorder of parathyreoidea. Symptoms caused by hypocalcemia are dominant and they are sign of disturbed neuromuscular balance. Alopecia is frequent disorder which occurs in the course of the illness. We report a case of five year old girl sent from Mostar because seizures incurable by phenobarbitone. Total alopecia was obvious. At admission total serum calcium level was 1.23 mmol/l. The level of parathormon was measured two times, and both results were under lowest value of normal range (< 10 pg/ml). After introducing calcitriol (Rocaltrol) in therapy, serum calcium level was almost normal and child was without symptoms. PMID- 11219920 TI - [Information model of activities of medical service headquarters in peacetime]. PMID- 11219921 TI - [Methodological approaches to organization of paid medical services]. PMID- 11219919 TI - [The blue sclera syndrome (Van der Heave syndrome)]. AB - Authors in this paper present two cases of Van der Heave syndrome, congenital disease of connective tissues and myopia with astigmatismus. There are usually other problems, affecting different systems. We tried treatment with soft torus contact lenses, with improved visual acuity at the follow up. PMID- 11219922 TI - [Medical consequences of earthquakes and organization of their liquidation (Communication II)]. AB - The main factor determining the size of sanitary losses (SL) and the share of injuries with different degree of severity is intensity of earthquake. At the same time dependence of SL structure on the types of populated area (including the peculiarities of their building) and the character of population allocation at the moment of earthquake is rather small. It allows to substantiate the common medical-and-evacuation indices of the casualties for the given intensity of earthquake. The normative indices given in the article are of reference significance and depending on concrete situation require closer definition. PMID- 11219923 TI - [Use of immunoenzyme test systems for diagnosis of syphilis in the troop unit of a medical service]. PMID- 11219924 TI - [Surgical approaches in acute pancreatitis]. PMID- 11219925 TI - [Standards in antibacterial therapy of hospital pneumonia]. PMID- 11219926 TI - [Current problems in medical support for provision of radiation and chemical safety in the Armed Forces]. AB - The events and changes of the last decade, appearance of new factors determining the character of professional activities of military doctors have become the cause of displace of some accents in organization of medical support of RF AF radiation and chemical security. The possibility to use chemical and radiation factors for military ends as well as wide spread of chemical substances and sources of ionizing radiation in human everyday activities during peacetime allow to confirm that protection of subject, society and state is closely connected with support of radiation and chemical security. Considerable widening of class of problems standing before medical service and their increased complexity make impossible medical support of radiation and chemical security of the RF AF staff with forces and means of specialists working only in one field (toxicologists radiologists). Such complex problem requires the conduction of scientifically well-founded, effective measures based on the knowledge of specific effects of radiation and chemical factors on human body. PMID- 11219927 TI - [Thrombogenesis and its prophylaxis]. PMID- 11219928 TI - [Local myoplasty with microsurgical tissue transplantation in treatment of calcaneus chronic osteomyelitis]. PMID- 11219929 TI - [Pharmacoeconomic estimation of cost of community acquired pneumonia therapy]. PMID- 11219930 TI - [Modern carried medical kits for military paratroopers]. PMID- 11219931 TI - [Treatment of pseudotuberculosis in military personnel (scientific basis and practical recommendations)]. AB - The efficiency of 22 schemes of etiotropic therapy including treatment courses of different duration and new methods was studied basing on the results of examination of 1376 patients and retrospective analysis of 2008 cases of pseudotuberculosis in servicemen. Critical review of literature dealing with this problem was conducted. The causes of contradictory literary data have been revealed. Specificity of military service and pseudotuberculosis pathogenesis influencing on disease course and efficiency of its treatment has been shown. Taking into account our own investigations and analysis of literature there was developed the scheme of differentiated etiopathogenetic therapy of pseudotuberculosis with the use of original approaches including the method of two-stage intermittent antimicrobial therapy, stepped (parenteral-oral) etiotropic therapy, antihypoxants, gg-ABA-ergic and nootropic agents, adaptogenes, dose increase of physical load, new physiotherapeutic methods, endolymphatic administration of antibiotics. PMID- 11219932 TI - [Passive orthostatic test in evaluation of efficiency of medical rehabilitation of flying personnel]. PMID- 11219933 TI - [Assessment of the health of the salvaging personnel at the Chernobyl Nuclear Power Plant: findings of the Russian Federal Interdepartmental Expert Committee for 1999]. PMID- 11219934 TI - [Prognosis of oncologic morbidity among the salvaging personnel at the Chernobyl Nuclear Power Plant]. PMID- 11219935 TI - [Radiologic diagnosis of stomach cancer. Critical analysis of deeply rooted misconceptions]. PMID- 11219936 TI - [Current problems of dose-time correlation in delayed radiotherapy of cancer]. PMID- 11219937 TI - [Comparison of diagnostic significance of bone and bone marrow scintigraphy in patients with Hodgkin disease]. AB - Diagnosis of skeletal tumors in patients with Hodgkin's disease is of paramount importance for precise staging of tumor process, prognosis and choice of optimal treatment. At present, according to the International Union Against Cancer (UICC), scintigraphy of bones and bone marrow is not regarded as a standard examination procedure for this pathology. We believe, however, that the sensitivity, specificity and overall accuracy of this procedure for bone marrow examination are 91.4; 94.8 and 92.9%, while those of osteoscintigraphy--49.1; 97 and 80.6%, respectively. According to our statistics (based on chi-square-test), the sensitivity and overall accuracy of osteoscintigraphy were significantly lower (p < 0.05) than those of bone marrow scintigraphy. The specificity (100%) of bone marrow trepanobiopsy is beyond doubt. However its sensitivity (36%) and overall accuracy (70.7%) were significantly lower (p < 0.05) than those of bone marrow scintigraphy (based on chi-square-test). Therefore, since the results of bone marrow scintigraphy are comparable to those of MRT which, like bone marrow trepanobiopsy, is a component of the diagnostic standard procedure approved by the UICC, bone marrow scintigraphy should be recommended for assaying the extent of involvement in Hodgkin's disease. PMID- 11219938 TI - ["Interventional radiology" in breast examination]. AB - The data on such highly-effective invasive diagnostico-therapeutic procedures as ductography, sclerosing-solution cystography, X-ray-controled puncture biopsy, stereotactical computer technique, sonography and preoperative maging of nonpalpable lesions were analyzed following a complex mammographic examination of 20,000 patients with different breast pathologies. Advantages offered by complex breast examination are discussed. Among them were the use of optimal effects of each invasive procedure, an accuracy of preoperative diagnosis reaching 95-98% (nonpalpable breast lesions included) and a significantly reduced extent of breast surgery. PMID- 11219939 TI - [The role of computerized tomography in the diagnosis of primary lung cancer]. AB - A CT-examination of 87 patients with various types of central cancer of the lung was carried out. Computed-tomography scanning is a highly-sensitive method of radiodiagnosis which detects respiratory system lesions, stage, predominant area of involvement and condition of adjacent tissues. On the basis of CT-related features of tumor, type and stage can be identified to choose optimal therapy and follow-up. PMID- 11219940 TI - [Postoperative computerized tomography of thoracic organs in lung cancer patients]. AB - The report discusses the data on the complex radiation examination of 40 lung cancer patients at different stages of postoperative follow-up. Standard X-ray procedures and CT of thoracic organs were carried out. Considerable advantages offered by CT were recorded in the assessment of the pleural cavity, the remaining part of the lung and mediastinal organs. CT evidence played an important role in making differential diagnosis of relapse and other postoperative changes. PMID- 11219941 TI - [Invasive radiology in the diagnosis and treatment of benign breast diseases]. AB - 100% of cases of cystic breast disease were effectively diagnosed using high-tech complex examination procedures. The most efficient invasive methods of diagnosis and therapy are discussed. Surgery was reduced to 88% due to application of sclerosing-solution techniques for conservative treatment of breast cysts. PMID- 11219942 TI - [Problems in the radiologic diagnosis of osteogenic sarcoma]. AB - Osteogenic sarcoma showing the signs of acute osteolytic process were hardest to diagnose. Since-reliable diagnosis depended on detection of neoplastic osteogenesis in involved bone, tomography proved to be of vital importance. Differential diagnosis was instrumental in dealing with osteolytic giant-cells and osteomyelitis. Diagnosis cannot be considered complete until histological examination is carried out. Whenever neoplastic osteogenesis is suspected, samples must be taken from relevant sites. PMID- 11219943 TI - [Conservative therapy for early-stage breast cancer]. AB - An evaluation of the data on the treatment of 298 cases of breast cancer (stages IIa and IIb) showed that a reduced frequency of loco-regional recurrences, after post-operative irradiation as a component of conservative therapy, was followed by improvement in quality of life. This was particularly apparent in patients with pT2pN1 tumors. It was also found that after extended dissection of axillary lymph nodes at all three levels, a dose of 50 Gy was sufficient without additional irradiation of the cicatrix. Nor was it necessary to expose the axillary area in cases of three or less lymph node recurrences provided that at least 6 resected nodes were studied histologically. Following conservative therapy, 5-year survival was 97%, while relapse-free survival--82%. PMID- 11219944 TI - [Thermotherapy for laryngeal cancer]. AB - An analysis of the data on the treatment of 91 cases of advanced cancer of the larynx showed that local UHF-hyperthermotherapy is more efficient than the SHF one as a component of radiotherapy. Use of the latter procedure was followed by a higher rate of late-onset radiation injuries. Moreover, combined application of hyper-fractionated irradiation and UHF-hyperthermotherapy involved practically no grave complications while 5-year survival increased. PMID- 11219945 TI - [Automated radiotherapy in the combined treatment of locally advanced and disseminated ovarian cancer]. AB - The paper deals with the results of treatment of 110 patients with advanced ovarian cancer showing signs of tumor progression following polychemotherapy with two regimens which included radiotherapy. Variants of distant and contact irradiation individually-tailored to suit the types of tumor are discussed. Details of single and repeated courses of chemoradiation are presented. Such beneficial effects as longer survival and better quality of life were registered in 76%. PMID- 11219946 TI - [Experience with and perspectives of an extended radical regimen of radiotherapy for Hodgkin's disease with prophylactic irradiation of the liver and the lungs]. AB - The end-results of extended radical radiotherapy for stage II-III Hodgkin's disease with apparent factors of risk of relapse in the lung and/or liver are presented. The procedure included prophylactic irradiation of both organs. Ten year relapse-free survival in the lung-irradiation group was 85.9%, overall 10 year survival--94.0%; the liver-irradiation group--90.0 and 94.7%, respectively. Preventive irradiation was shown to significantly decrease the influence of such risks as extended lesions of the mediastinum and spleen. Relapse in the lung was recorded in one case (1.6%) only, with no tumor progression defected in the liver. Significant increase in 5- and 10-year relapse-free survival was established in the lung-irradiation group, as a result of a comparison of the study group and that of controls who showed characteristic signs of intrathoracic risk. Significant difference in overall survival was recorded for the first three years only. As far as the liver-irradiation factor is concerned, the rise in both categories of survival was significant for the 10 years. It is suggested that patients with stage II-III Hodgkin's disease receive prophylactic irradiation whenever they reveal significant signs of risk of relapse in the lung and/or liver. PMID- 11219947 TI - [Radiotherapy for brain stem neoplasms in children]. AB - The immediate and short-term results of radiotherapy of brain stem tumors in 24 children were evaluated. All the patients were able to sustain treatment due to adjuvant support with dehydrating and hormonal drugs, and beneficial clinical effect was recorded in 80%. However, MRT showed no decrease in tumor size. Tumor growth relapsed 3-8 months after radiotherapy. Although total dose ranged 60-72 Gy in 19 patients, there was clinical evidence of radiation injury. PMID- 11219948 TI - [From a mammographic station to the organization of the Federal Mammologic Center]. AB - The history of radiation application for breast cancer diagnosis in Russia is illustrated by an experience gained at the Center. It was concerned with designing specialized X-ray equipment as well as development of Standards to be used at mammographic stations. Teaching programs were devised for training X-ray diagnosis specialists with all necessary qualification to operate high-tech equipment of a mammographic station and to use a wide range of radiation and invasive procedures. PMID- 11219949 TI - [Some prognostic factors in the combined therapy of locally advanced breast cancer]. AB - A relationship between the dynamics of growth and pathological response of tumor cells and the number of neoadjuvant chemotherapy courses was established. As a result, there was no correlation between increase in overall and disease-free survival, on the one hand, and stage, on the other. An interval between neoadjuvant chemotherapy and surgery longer than 4 weeks had a negative effect on overall tumor response and duration of disease-free period. PMID- 11219950 TI - [Role of induction chemo- and radiotherapy in the treatment of locally advance breast cancer]. AB - 336 patients with locally-advanced breast cancer underwent neoadjuvant chemotherapy or chemoradiotherapy. Increase in T- and N-indices (change of stage after neoadjuvant chemotherapy) proved an important prognostic factor. Survival rates correlated with clinical effect and dropped as it diminished. This tendency was clear in both groups. There was no relationship between stage and overall and disease-free survival rates at early stages but later they declined as T- and N indices decreased. PMID- 11219951 TI - [Correlation of clinical effect, pathological response of tumor cells and the end results of combined treatment of locally advanced breast cancer]. AB - A correlation was established between the end-results of neoadjuvant chemotherapy for locally-advanced breast cancer and pathological response of tumor cells. Also, the end-results correlated with CR or PR and pathological response. Only a small proportion of patients with tumor progression were registered as stage III or IV of pathological response (0.6 and 0.8%, respectively). PMID- 11219952 TI - [Diagnosis and therapy of cancer of Vater's ampulla]. PMID- 11219953 TI - [The use of therapeutic/prophylactic dragee "honey laminolact" in radiotherapy of uterine tumors]. AB - The study deals with the effect of a newly-developed food product--Honey Laminolact, containing live lactic acid bacteria, amino acids, trace elements, fruit pectine and immunomodulators-on the degree of response to radiation in 44 patients who received radiotherapy for uterine tumors. It was shown to lower response of the intestinal tract to radiation when the small pelvis was exposed. PMID- 11219954 TI - Regularity effects in word naming: what are they? AB - In a word-naming experiment, word-body consistency was crossed with grapheme-to phoneme regularity to test predictions of current models of word recognition. In the latency and error data, a clear effect of consistency was observed, with the influence of regularity somewhat weaker. In addition, simulation data from three contemporary models of word recognition were obtained for the stimuli used in the experiment in order to compare the models' latencies with those of humans. The simulations showed that the human latency data are most consistent with the parallel-distributed-processing model of Plaut, McClelland, Seidenberg, and Patterson (1996), less so with the dual-process model (Zorzi, Houghton, & Butterworth, 1998), and least so with the dual-route-cascaded model (Coltheart & Rastle, 1994). PMID- 11219955 TI - Morphological priming: dissociation of phonological, semantic, and morphological factors. AB - Previous experiments based on a masked-priming paradigm revealed robust morphological priming effects induced by two derivational morphemes in Hebrew: the root and the verbal pattern. However, considering the special characteristics of the masked-priming paradigm, the possible contributions of phonological and/or semantic factors to these morphological effects could not be firmly assessed. In the present study, the role of these factors in morphological priming was examined, using cross-modal presentation. Experiment 1 revealed that priming between morphologically related words in Hebrew is determined by higher level linguistic characteristics and cannot be reduced to phonological overlap. Experiment 2 confirmed that morphological priming occurs in Hebrew even when primes and targets are not semantically related but, nevertheless, increases with semantic similarity. The results support the claim that morphological priming cannot be accounted for by considering semantic and phonological factors alone, and they exemplify the potential of using both masked and cross-modal priming to examine morphological processing. PMID- 11219957 TI - Syntactic priming in spoken production: linguistic and temporal interference. AB - Current evidence about the persistence of syntactic priming effects (Bock, 1986) is equivocal: Using spoken picture description, Bock and Griffin (2000) found that it persisted over as many as 10 trials; using written sentence completion, Branigan, Pickering, and Cleland (1999) found that it dissipated if even a single sentence intervened between prime and target. This paper asks what causes it to be long lasting. On one account, the rapid decay evidenced by Branigan et al. occurs because the task emphasizes conceptual planning; on another account, it is due to the written nature of their task. If conceptual planning is the cause, this might relate to planning the prime sentence or planning an intervening sentence. Hence we conducted an experiment with spoken sentence completion, contrasting no delay, an intervening sentence, and a pure temporal delay. The results indicated that strong and similar priming occurred in all three cases, therefore lending support to the claim that spoken priming is long lasting. PMID- 11219956 TI - Orthography plays a critical role in cognate priming: evidence from French/English and Arabic/French cognates. AB - A series of three experiments was carried out in order to better characterize the representations that support long-term cognate priming. In Experiment 1, robust priming was obtained between orthographically similar French/English cognates in bilingual speakers, and this priming was mediated, in part, by orthographic codes, given that priming for these items was dramatically reduced following a study-test modality shift. In Experiment 2, no priming was obtained between the same set of French/English cognates in monolingual English speakers. Finally, in Experiment 3, priming for orthographically unrelated Arabic/French cognates was no larger than cross-modal priming, suggesting that these effects were mediated by nonorthographic representations. The role of orthography in supporting cognate priming is discussed. PMID- 11219958 TI - Task demands and representation in long-term repetition priming. AB - The effects of task demands on the representation of letter strings in long-term repetition priming (LTRP) were explored in two lexical decision experiments. The stimuli in both experiments were words and nonwords, some presented horizontally and some vertically. The only difference between the two experiments was the response required by the participant. In Experiment 1, the participants pressed one of two buttons, indicating whether or not a given stimulus was a word. In Experiment 2, the participants pressed one of four buttons, indicating both the lexical status and the orientation of a given stimulus. The results were that in Experiment 1, LTRP was not disrupted by a change in stimulus orientation, whereas in Experiment 2 it was, suggesting that the nature of the stimulus representation utilized in LTRP is partially dependent on the demands of the task. PMID- 11219959 TI - Temporal and spatial distance in situation models. AB - In two experiments, we investigated how readers use information about temporal and spatial distance to focus attention on the more important parts of the situation model that they create during narrative comprehension. Effects of spatial distance were measured by testing the accessibility in memory of objects and rooms located at differing distances from the protagonist's current location. Before the test probe, an intervening episode was inserted in the narrative. Story time distance was manipulated by stating that the intervening episode lasted for either minutes or hours. Discourse time--that is, time spent reading from prime to test--was manipulated by describing the intervening episode either briefly or at length. Clear effects of story time distance and spatial distance on accessibility were found, whereas discourse time distance did not affect accessibility. The results are interpreted as supporting constructionist theories of text comprehension. PMID- 11219960 TI - Learning artificial grammars: no evidence for the acquisition of rules. AB - Two experiments investigated whether there is evidence for acquisition of rules in implicit artificial grammar learning (AGL). Two different methods were used in meeting this goal, multiple regression analysis and analysis of receiver operating characteristics (ROCs). By means of multiple regression analysis, several types of knowledge were identified that were used in judgments of grammaticality, for example, about single letters and about larger stimulus fragments. There was no evidence for the contribution of rule knowledge. The ROCs were in accord with a similarity-based account of AGL and thus did not support the notion that rule knowledge is acquired in AGL either. Simulations with a connectionist model corroborated the conclusion that the results were in accord with a similarity-based, associative account. PMID- 11219961 TI - Sex differences in duration judgments: a meta-analytic review. AB - We quantitatively reviewed human sex differences in the magnitude and variability of duration judgments. Data from 4,794 females and 4,688 males yielded 87 effect size estimates of magnitude and 28 of variability. The overall sex difference in duration judgment magnitude was small but statistically significant. It was moderated by whether study participants knew in advance (prospective paradigm) or only later (retrospective paradigm) that they would be required to judge duration. Although prospective judgments showed no overall sex effect, some levels of moderator variables showed a small but statistically significant effect. Retrospective judgments showed a larger subjective-to-objective duration ratio for females than for males, and several variables moderated this effect. Females' judgments also showed more intersubject variability than did males' judgments. Relative to males, females sustain attention to time more in the prospective paradigm and have better episodic memory in the retrospective paradigm. PMID- 11219962 TI - Predicting individual false alarm rates and signal detection theory: a role for remembering. AB - The relationships between hit, remember, and false alarm rates were examined across individual subjects in three remember-know experiments in order to determine whether signal detection theory would be consistent with the observed data. The experimental data differed from signal detection predictions in two critical ways. First, remember reports were unrelated, or slightly negatively related, to the commission of false alarms. Second, both response types (remembers and false alarms) were uniquely related to hit rates, which demonstrated that the hit rate cannot be viewed as the result of a single underlying strength process. These results are consistent with the dual-process signal detection model of Yonelinas (1994), in which performance is determined by two independent processes--retrieval of categorical context information (remembering) and discriminations based on continuous item strength. Remember and false alarm rates selectively tap these processes, whereas the hit rate is jointly determined. Monte Carlo simulations in which the dual-process model was used successfully reproduced the pattern in the experimental data, whereas simulations in which a signal detection model, with separate "old" and "remember" criteria, was used, did not. The results demonstrate the utility of examining individual differences in response types when one is evaluating memory models. PMID- 11219964 TI - On the locus of the semantic satiation effect: evidence from event-related brain potentials. AB - The present study sought to determine whether semantic satiation is merely a by product of adaptation or satiation of upstream, nonsemantic perceptual processes or whether the effect can have a locus in semantic memory. This was done by measuring event-related brain potentials (ERPs) in a semantic word-detection task involving multiple presentations of primes and critical related and unrelated words in three experiments involving visual (Experiment 1) and auditory (Experiments 2A and 2B) stimuli. Primes varied in their type case (Experiment 1) or pitch (Experiment 2B) in order to discourage sensory adaptation. Prime satiation and relatedness of the primes to the critical word had interacting effects on ERP amplitude to critical words, particularly within the time-window of the N400 component. Because numerous studies have indicated a role for the N400 in semantic processing, modulation of the N400 relatedness effect by prime satiation (with little or no contribution from perceptual adaptation) suggests that semantic memory can be directly satiated, rather than the cost to semantic processing necessarily resulting from impoverishment of perceptual inputs. PMID- 11219965 TI - The role of salience in conceptual combination. AB - The present study investigated three factors that affect the interpretation of novel noun-noun (N-N) combinations: simple feature salience, ontological category, and assessed similarity. Participants read and defined a series of novel N-N combinations in which the feature salience of N1 and N2 was manipulated. Participants also rated the combinations for similarity. The combinations were constrained to be within ontological category. All interpretations were scored in terms of the strategies (property mapping vs. relation linking) used to produce the given interpretations. Highly salient features drove property-mapping interpretations based on those features. Natural kinds produced more property-mapping interpretations than did artifacts. There was no correlation between the proportion of property-mapping interpretations and the assessed similarity of the N-N combinations. These results are discussed as an extension of Estes and Glucksberg's (2000) interactive theory of conceptual combination and argue for the importance of feature salience as a factor in conceptual combination. PMID- 11219963 TI - Acute effects of triazolam on false recognition. AB - Neuropsychological, neuroimaging, and electrophysiological techniques have been applied to the study of false recognition; however, psychopharmacological techniques have not been applied. Benzodiazepine sedative/anxiolytic drugs produce memory deficits similar to those observed in organic amnesia and may be useful tools for studying normal and abnormal memory mechanisms. The present double-blind, placebo-controlled repeated measures study examined the acute effects of orally administered triazolam (Halcion; 0.125 and 0.25 mg/70 kg), a benzodiazepine hypnotic, on performance in the Deese (1959)/Roediger-McDermott (1995) false recognition paradigm in 24 healthy volunteers. Paralleling previous demonstrations in amnesic patients, triazolam produced significant dose-related reductions in false recognition rates to nonstudied words associatively related to studied words, suggesting that false recognition relies on normal memory mechanisms impaired in benzodiazepine-induced amnesia. The results also suggested that relative to placebo, triazolam reduced participants' reliance on memory for item-specific versus list-common semantic information and reduced participants' use of remember versus know responses. PMID- 11219966 TI - Attribute centrality and imaginative thought. AB - Participants' representations of the concept human were examined to differentiate three types of associations between concepts and their component attributes: the capacity of concepts to cue attributes (attribute accessibility), the capacity of attributes to cue concepts (instance accessibility), and the extent to which attributes are thought of as central to concepts (attribute centrality). The findings provide information about the concept human itself and, more generally, about the functionally distinct roles those different attribute-concept associations play in guiding imaginative thought. College students listed attributes that differentiate humans from other animals, rated the centrality of those attributes, and listed animals that possess those attributes. Other students drew and described extraterrestrials that possessed some of the attributes that were found to vary across those listing and rating tasks. Rated centrality was the most important determinant of an attribute's impact on imaginative generation. When the imagined extraterrestrials were supposed to possess attributes that had been rated as central to humans (intelligence, emotional complexity, or opposable thumbs), participants projected more aspects of human form onto them than when the creatures were supposed to possess less central attributes or when attributes were unspecified. PMID- 11219967 TI - Levels-of-processing effects on Chinese character completion: the importance of lexical processing and test cue. AB - The levels of processing (LoP) effect was studied in Chinese character completion tasks. The same stem cue, either graphemically or semantically related to the target character, was used to generate either a perceptual or a conceptual test. Participants received either direct or indirect instructions, so that the same stem cue also produced either an explicit or an implicit test of memory. This allowed us to examine simultaneously the roles of perceptual versus conceptual test and retrieval intentionality in the LoP effect. No LoP effects were found when the memory test was implicit. LoP effects were also not found for stems and characters related graphemically (perceptually), but were found for stems and characters related semantically (conceptually) when the memory test was explicit. The results are discussed in terms of the importance of lexical processing for character completion tests and the importance of reinstatement of the study process during retrieval for explicit memory tests. PMID- 11219968 TI - Effects of hearing words, imaging hearing words, and reading on auditory implicit and explicit memory tests. AB - In four experiments, we examined the degree to which imaging written words as spoken by a familiar talker differs from direct perception (hearing words spoken by that talker) and reading words (without imagery) on implicit and explicit tests. Subjects first performed a surface encoding task on spoken, imagined as spoken, or visually presented words, and then were given either an implicit test (perceptual identification or stem completion) or an explicit test (recognition or cued recall) involving auditorily presented words. Auditory presentation at study produced larger priming effects than did imaging or reading. Imaging and reading yielded priming effects of similar magnitude, whereas imaging produced lower performance than reading on the explicit test of cued recall. Voice changes between study and test weakened priming on the implicit tests, but did not affect performance on the explicit tests. Imagined voice changes affected priming only in the implicit task of stem completion. These findings show that the sensitivity of a memory test to perceptual information, either directly perceived or imagined, is an important dimension for dissociating incidental (implicit) and intentional (explicit) retrieval processes. PMID- 11219969 TI - The ability of familiarity, disruption, and the relative strength of nonenvironmental context cues to explain unreliable environmental-context dependent memory effects in free recall. AB - The ability of environmental-context (EC) familiarity, movement disruption, and the relative strength of memory cues to explain unreliable EC-dependent free recall memory effects was examined in two experiments. Experiment 1 replicated Smith's (1979, Experiment 1) results confirming that familiarity and disruption cannot account for free-recall EC-reinstatement effects. In Experiment 2, a level of processing manipulation varied stimulus item memory cue strengths, and memory was again assessed by free recall. Contrary to Murnane and Phelps's (1995) and Dougal and Rotello's (1999) recognition findings, an EC-reinstatement effect was observed with low, but not high, levels of processing. However, comparisons across the two experiments revealed inconsistencies with the relative cue strength hypothesis. Consequently, a variant of the relative cue strength hypothesis that highlights the role of retrieval processes was proposed to explain the interaction between the levels of processing and the EC-reinstatement effect. PMID- 11219970 TI - Deeper processing at target selection increases the magnitude of negative priming. AB - Do deeper levels of processing produce equivalent priming effects at all stages of task performance? In Experiment 1, we varied the level of processing factorially across two task stages--target selection and response selection. Each stage required perceptual (e.g., color) or conceptual (e.g., friendliness) processing of stimulus items (i.e., animal names). Negative priming was substantially greater when deeper processing was required at the target selection stage, but it was unaffected by the level of processing at the response selection stage. In contrast, positive priming was greater when deeper processing was required at the response selection stage, but it was unaffected by processing at the target selection stage. In Experiment 2, we generalized this finding using a task in which numeric targets were selected on the basis of their parity. As in Experiment 1, the deeper level of processing at the target selection stage produced a larger negative priming effect. These results illuminate the role of target selection demands in modulating the strength of negative priming. PMID- 11219971 TI - The Stroop effect: it is not the robust phenomenon that you have thought it to be. AB - Five experiments demonstrate that context has a powerful effect on the ease with which people can name (Experiments 1-3) or categorize (Experiments 4-5) a stimulus while ignoring another stimulus, irrelevant or conflicting with the target. Selectivity of attention to the target dimension was gauged through Stroop and Garner effects. When the stimulus values along the target dimension and the to-be-ignored dimension were correlated over the experimental trials, large effects of Stroop and Garner influenced performance. However, when random allocation of values created zero dimensional correlation, the Stroop effects vanished. These results imply that when the nominally irrelevant dimension is in fact correlated with the relevant dimension, participants then attend to the irrelevant dimension and thus open themselves up to Stroop interference. Another variable of context, the relative salience of the constituent dimensions, also affected performance with the more discriminable dimension disrupting selective attention to the less discriminable dimension. The results demonstrate the importance of context in engendering the failure of selective attention and challenge traditional automaticity accounts of the Stroop effect. PMID- 11219972 TI - Biochemical modulation of 5-FU in systemic treatment of advanced colorectal cancer. AB - Randomized studies have tested a variety of strategies to improve the activity of 5-fluorouracil (5-FU) in colorectal cancer patients. Results from 14 randomized trials comparing 5-FU administered via intravenous (i.v.) bolus either as a single agent or modulated by leucovorin indicate a significantly higher response rate with 5-FU/leucovorin (25% vs 13% of assessable patients). Sequential methotrexate followed by i.v. bolus 5-FU is associated with a higher response rate. Continuous infusion schedules also produce superior response rates compared to bolus 5-FU alone. Published meta-analyses indicate a small, but statistically significant, survival advantage for methotrexate/5-FU and infusional 5-FU, but not for leucovorin-modulated 5-FU. Although the incidence of hand-foot syndrome is higher with protracted infusional 5-FU, the incidence of other toxicities including myelosuppression, diarrhea, and mucositis is low. Oral administration of 5-FU may simulate infusional schedules while avoiding catheter-related complications. PMID- 11219973 TI - Clinical implications of dihydropyrimidine dehydrogenase on 5-FU pharmacology. AB - Dihydropyrimidine dehydrogenase (DPD) is the initial rate-limiting enzyme in the catabolism of 5-fluorouracil (5-FU), accounting for catabolism of over 85% of an administered dose of 5-FU. DPD plays an important role in regulating the availability of 5-FU for anabolism. DPD also accounts for much of the variability observed with the therapeutic use of 5-FU. This includes variable 5-FU levels over 24 hours during a continuous infusion; the widely reported variability in the pharmacokinetics of 5-FU; the observed variable bioavailability that led to the recommendation that 5-FU not be administered as an oral agent; and lastly, the observed variability in both toxicity and drug response (resistance) after identical 5-FU doses. Knowledge of the DPD level, as well as the levels of other potentially important molecular markers (e.g., thymidylate synthase), may permit adjustments or modulation of the 5-FU dose that can result in an increase in the therapeutic efficacy of 5-FU. PMID- 11219974 TI - Oral chemotherapy for colorectal cancer: some economic considerations. AB - In the formal medical curriculum, little has been provided to prepare the clinician for an understanding of the economics of health care. The questions are often far more complicated than they initially appear to be, and the techniques and terminology used in evaluation of these questions are often foreign to many health-care providers. This brief essay, written by an author who confesses to being an economic layman, will attempt to discuss and clarify some terms and techniques used in the economic analysis of health care. In that context, and recognizing the limitations of the techniques available, an attempt will be made to address the question of the economic impact of oral fluorinated pyrimidines on the management of colorectal cancer. PMID- 11219975 TI - Patient selection for oral chemotherapy. AB - Oral chemotherapy has evolved with several new agents such as capecitabine and UFT in active clinical trials or already approved for use in the western world. Several distinct issues, apart from the usual criteria for selecting patients for intravenous chemotherapy, dictate patient selection for these drugs. This article discusses these issues, which include patient preference, selection, and compliance. PMID- 11219976 TI - Nursing strategies for patients on oral chemotherapy. AB - Oncology nurses play a pivotal role in educating the cancer patient who is about to commence oral chemotherapy. Increasing numbers of patients are receiving oral chemotherapy at home, and with this move to oral self-administration, there has been a critical shift in responsibility of management from the provider to patient. Oral regimens pose new challenges in patient selection and education. Recognition of factors that affect patient compliance will be particularly important with oral chemotherapy. Strategy tools for the patient and provider will need to be developed to ensure optimal compliance and safety. PMID- 11219978 TI - UFT in the treatment of colorectal and breast cancer. AB - UFT and leucovorin (Orzel) is a combination of tegafur and uracil in a molar ratio of 1:4. Tegafur, a prodrug of 5-fluorouracil (5-FU), is converted to 5-FU by the hepatic cytochrome P450 pathway, whereas uracil enhances the half-life of converted 5-FU leading to prolonged exposure and higher intracellular concentration of 5-FU by inhibiting dihydropyrimidine dehydrogenase (DPD), a rate limiting enzyme in 5-FU catabolism. UFT has broad antitumor activity against colorectal and breast cancer, and has been studied extensively worldwide. Trials conducted in the United States have mainly focused on the combination of UFT and leucovorin. Compared with an intravenous 5-FU plus leucovorin regimen in advanced colorectal cancer treatment, UFT plus leucovorin appears to have equivalent antitumor efficacy with less toxicity. UFT may also provide a more convenient protracted treatment method with fewer complications, compared to intravenous programs. The application for FDA approval of UFT with leucovorin as a first-line treatment regimen for advanced colorectal cancer is pending. Administered as a single agent or in combination with other chemotherapy agents and hormones, UFT may also be effective in treating breast cancer, either as a primary adjuvant treatment or as palliative treatment for metastatic disease. PMID- 11219977 TI - Capecitabine in colorectal cancer. AB - Capecitabine (Xeloda) is the first orally available fluoropyrimidine approved for use in patients with cancer. It was initially approved for use in metastatic breast cancer, but significant data also support its use in the management of metastatic colorectal cancer. Capecitabine relies on a series of metabolic steps, the last of which occurs primarily within cancer cells. This results in selective activation of the compound within cancer cells, thereby reducing systemic toxicities and allowing for greater dose intensity. This article reviews selected phase I, phase II, and phase III clinical trials conducted in patients with colorectal cancer that document the metabolic activation of this compound and support its use in patients with advanced colorectal cancer. PMID- 11219979 TI - Oral eniluracil/5-FU for advanced colon and breast carcinomas. AB - 5-fluorouracil (5-FU) is irreversibly catabolized to dihydrofluorouracil, an inactive metabolite, by the enzyme dihydropyrimidine dehydrogenase (DPD). This catabolic pathway is a critical step in determining 5-FU availability for conversion to nucleotides and eventual incorporation into either RNA or DNA. Inactivation of DPD, therefore, is an approach to enhance the availability of 5 FU for potential improved therapeutic effect. Preclinical animal and human studies have demonstrated that eniluracil is an effective inactivator of DPD. Phase I studies have been completed showing the tolerability of two dosing schedules, including (1) a chronic schedule with twice-daily administration of eniluracil plus oral fluorouracil (5-FU) (10:1 ratio) for 28 days, and (2) a schedule of eniluracil administered daily on days 1-7 with oral 5-FU once daily on days 2-6. The phase I trials have demonstrated limited toxicities including diarrhea, mucositis, and neutropenia. Follow-up clinical trials have targeted colon and breast cancers in particular. PMID- 11219980 TI - Other fluorinated pyrimidines in the treatment of solid tumors. AB - Researchers, primarily in Japan, Europe, and the United States, have evaluated several new fluorinated pyrimidines in recent years. Most of these drugs are orally active prodrugs of fluorouracil (5-FU), and some also contain modulators of its pharmacological properties. S-1 is a rationally developed combination of tegafur, a prodrug of 5-FU; CDHP, an inhibitor of 5-FU catabolism; and potassium oxonate, an inhibitor of 5-FU-induced diarrhea. S-1 underwent phase I and II trials in Japan, where it is now approved for use in the treatment of advanced gastric cancer. Two phase I studies conducted recently in Europe and the United States identified diarrhea as the dose-limiting toxicity of S-1. BOF-A2, which contains a 5-FU prodrug and CNDP, an inhibitor of 5-FU catabolism, demonstrated clinical activity in preliminary studies in Japan. This article summarizes the preclinical and clinical development of S-1 and BOF-A2. PMID- 11219981 TI - Clinical status of capecitabine in the treatment of breast cancer. AB - New treatment strategies for advanced breast cancer have focused on both the development of new molecular targets in breast cancer cells, as well as improving the therapeutic index of presently available therapy. The development of capecitabine (Xeloda), a new oral fluoropyrimidine, is an example of a chemotherapy drug that has single-agent activity in heavily pretreated patients with advanced breast cancer, with the added convenience of good oral bioavailability. Capecitabine is an excellent treatment option for patients who require symptom palliation and who prefer oral medications. The discussion that follows reviews the clinical data on the use of capecitabine in advanced breast cancer. PMID- 11219982 TI - Perspectives on fluorinated pyrimidine use in gastrointestinal and breast oncology. PMID- 11219983 TI - Oral fluoropyrimidine-based combination therapy in gastrointestinal cancer. AB - Significant emphasis has been placed recently on designing more effective fluorouracil (5-FU)-based combination protocols for gastrointestinal cancer. Promising results were seen with 5-FU/leucovorin in combination with irinotecan (Camptosar) or oxaliplatin (Eloxatin), especially in colorectal cancer. Clinical trials of UFT, with or without leucovorin, demonstrate the safety of this regimen and an efficacy comparable to that of bolus 5-FU/leucovorin in the treatment of gastrointestinal tumors. Two large randomized phase III trials of capecitabine (Xeloda) showed that capecitabine also offers a convenient alternative to bolus 5 FU/leucovorin with a superior safety profile and at least equivalent antitumor activity. PMID- 11219984 TI - Public perception of science. Part 1. PMID- 11219985 TI - In space, the past can be recast but not the present. AB - We address the relationship between perception and spatial, working memory. Specifically, we argue that perceptual experience following the creation of a representation of target location affects it in a systematic way. We designed a motor task in which observers had to point to the initial or final position of a horizontally drifting target embedded in a vertically drifting background. The target was perceived as having an illusory motion component in a direction opposite that of the inducer dots [Duncker, 1938, Source Book of Gestalt Psychology (London: Kegan Paul, Trench, Trubner and Co)]. For both positions, there was an identical time delay before the observer could respond. Nonetheless, estimates of the initial target position were significantly biased by the illusion in a direction opposite the perceived target motion, and both bias and variability were significantly greater than those of the target's final position. In prior studies on positional accuracy with induced displacement, a delay before a pointing response led to an unbiased position estimate obtained without delay to become biased, leading investigators to argue for a long-lasting, inaccurate cognitive system that overrules an accurate, nonetheless transient, motor one (Bridgeman et al, 1997, Perceptual Psychology 59 456-469). Since the same motor task with identical delay on either position yielded different outcomes, a hypothesis based on distinct motor and cognitive representations of visual space is untenable here. Instead, we argue that an online representation of the target's original position is updated in an ongoing fashion in order to reconcile the perceived illusion with the veridically perceived present (current target location). PMID- 11219986 TI - Manipulation of colour and shape information and its consequence upon recognition and best-likeness judgments. AB - Previous forays into the study of recognition have revealed an advantage for line drawn and photographic shape caricatures of faces in reaction-time paradigms. When a presentation-time technique was used, photographs with enhanced colour intensity and saturation were also found to provide superior recognition accuracy to veridical images. This has provided strong evidence that distinctive information can produce a recognition advantage for famous faces in both colour and shape domains. Such a presentation-time paradigm allows the display of stimuli over a range of brief display periods. Using this paradigm, subjects recognised photorealistic target faces caricatured in shape with greater accuracy than veridical images, consistent with previous findings when reaction time was used as a measure. Subjects were also asked to identify the best likeness for individuals using photorealistic stimuli and an interactive paradigm with shape caricature, colour caricature, and contrast control varied by the user in real time. The best likeness with shape manipulation was a slight anticaricature, while with colour-caricature and contrast-control images a mildly exaggerated image was selected as the best likeness. Thus, although images caricatured substantially in colour or shape (+40%) induce superior recognition compared to veridical images, such substantial exaggerations are not necessarily seen as best likenesses under prolonged exposure. PMID- 11219987 TI - Perceiving binocular depth with reference to a common surface. AB - A common surface is a spatial regularity of our terrestrial environment. For instance, we walk on the common ground surface, lay a variety of objects on the table top, and display our favorite paintings on the wall. It has been proposed that the visual system utilizes this regularity as a reference frame for coding objects' distances. Presumably, by treating the common surface as such--i.e. an anticipated constant--the visual system can reduce its coding redundancy, and divert its resources to representing other information. For intermediate-distance space perception, it has been found that absolute distance judgment is most accurate when a common ground surface is available. Here we explored if the common surface also serves as the reference frame for the processing of binocular disparity information, which is a predominant cue for near-distance space perception. We capitalized on an established observation where the perceived slant of a surface with linear binocular-disparity gradient is underestimated. Clearly, if the visual system utilizes this incorrectly represented slant surface as a reference frame for coding the objects' locations, the perceived depth separation between the objects will be adversely affected. Our results confirm this, by showing that the depth judgment of objects (two laterally separated vertical lines) on, or in the vicinity of, the surface is underestimated. Furthermore, we show that the impact of the common surface on perceived depth separation most likely occurs at the surface-representation level where the visual surface has been explicitly delineated, rather than at the earlier disparity-processing level. PMID- 11219988 TI - The effects of age upon the perception of depth and 3-D shape from differential motion and binocular disparity. AB - The ability of younger and older adults to perceive the 3-D shape, depth, and curvature of smooth surfaces defined by differential motion and binocular disparity was evaluated in six experiments. The number of points defining the surfaces and their spatial and temporal correspondences were manipulated. For stereoscopic sinusoidal surfaces, the spatial frequency of the corrugations was also varied. For surfaces defined by motion, the lifetimes of the individual points in the patterns were varied, and comparisons were made between the perception of surfaces defined by points and that of more ecologically valid textured surfaces. In all experiments, the older observers were less sensitive to the depths and curvatures of the surfaces, although the deficits were much larger for motion-defined surfaces. The results demonstrate that older adults can extract depth and shape from optical patterns containing only differential motion or binocular disparity, but these abilities are often manifested at reduced levels of performance. PMID- 11219989 TI - Mapping the zone of eye-height utility for seated and standing observers. AB - In a series of experiments, we delimited a region within the vertical axis of space in which eye height (EH) information is used maximally to scale object heights, referred to as the "zone of eye height utility" (Wraga, 1999b Journal of Experimental Psychology, Human Perception and Performance 25 518-530). To test the lower limit of the zone, linear perspective (on the floor) was varied via introduction of a false perspective (FP) gradient while all sources of EH information except linear perspective were held constant. For seated (experiment 1a) observers, the FP gradient produced overestimations of height for rectangular objects up to 0.15 EH tall. This value was taken to be just outside the lower limit of the zone. This finding was replicated in a virtual environment, for both seated (experiment 1b) and standing (experiment 2) observers. For the upper limit of the zone, EH information itself was manipulated by lowering observers' center of projection in a virtual scene. Lowering the effective EH of standing (experiment 3) and seated (experiment 4) observers produced corresponding overestimations of height for objects up to about 2.5 EH. This zone of approximately 0.20-2.5 EH suggests that the human visual system weights size information differentially, depending on its efficacy. PMID- 11219990 TI - Emmert's law in the dark: active and passive proprioceptive effects on positive visual afterimages. AB - The relationship between apparent size and apparent distance is given by Emmert's law, which states that a retinal image is proportional in size to the distance of the surface it is projected upon. This principle also applies to retinal afterimages in that they, too, will change in apparent size if distance cues suggest that the location of the object onto the retinal image has been altered. It has also been known for some time that non-retinal cues can produce quantitative and qualitative effects on an afterimage when it is viewed in the dark. In the present two studies, positive afterimages of an observer's hand, as well as objects held by that hand, were used as targets to investigate the effects on size-constancy scaling of moving the hand to and fro along the line of sight for different distances in the dark. Results show that, when observers focus on a held object, the changes in size predicted by Emmert's law occur in response to both active and passive proprioceptive or haptic cues. The most intriguing result consisted of the finding that, when only the hand is the target, there appears to be a limit to the decrease in apparent hand size. It appears that the visual system 'refuses' to size-scale the hand below a limit it accepts as representative or acceptable of 'its' hand. PMID- 11219992 TI - Near the zone of totality: an eclipse observed. PMID- 11219991 TI - The multiple-faces phenomenon: some investigate studies. PMID- 11219993 TI - [Clinical nutrition: a science in evolution]. PMID- 11219994 TI - [Nutrition and chronic renal failure]. AB - The causes of malnutrition in chronic terminal kidney failure are reviewed in the situation both before and after dialysis, as are the malnutrition rates in both circumstances and their treatment. Malnutrition has a high prevalence in terminal kidney patients, partly as a result of the therapeutic restriction on calories and proteins, but also due to the metabolic reactions typical of the disease and to anorexia. In patients subjected to dialytical methods, certain other mechanisms are added. In addition to malnutrition, there are alterations in the metabolism of calcium, phosphorus and potassium, as well as lipids, thus limiting nutritional therapy's ability to restore the nutritional status to normal. An awareness of energy expenditure in chronic terminal kidney failure and the consequences of malnutrition have led to new challenges in nutritional therapy, both in the dose and quality of the proteins, with a debate raging over the advantages of ketoanalogues, and also in the methods for providing nutrients. The ideal nutritional method for repletion is oral administration, but this can be enhanced with artificial support such as oral supplements, parenteral nutrition during dialysis or such alternatives as enteral nutrition at home in the case of chronic kidney problems in children, using percutaneous endoscopic gastrostomy (PEG), in order to nourish the patients and minimize growth disorders. PMID- 11219995 TI - [Parenteral nutrition in hematologic patients treated with hematopoietic stem cell transplantation]. AB - The transplant of haematopoyetic parent cells is on common way of treating haematological neoplasias and other types of immunological and tumoural disorders. The aggressive nature of the treatment, leading to peculiar nutritional and metabolic conditions in these patients, as well as the notable incidence of complications, have meant that nutritional support is included in the therapeutic armoury. As in other clinical situations, we are currently able to go beyond merely ensuring the necessary nutritional support. We can also influence the progress of the illness by means of the provision of specific substrates which interfere in a positive manner with the disturbed intermediate metabolism. Even more, in some of these substrates we can find a nutrient drug action. PMID- 11219996 TI - [Multiple trauma and burns]. AB - Patients with multiple injuries and burns are the paradigm of critically-ill patients. Their cases are acute, severe and, fortunately, reversible in a large number of situations. The severe aggressions leading to this kind of condition is the rigger for a maelstrom of inflammatory mediators, metabolic and neuro endocrinal response, leading to an acceleration in the combustion of the injured organ. This "internal combustion" process takes nourishment from organic reserves, using them up and thus producing dysfunctions in various organs. This is where nutritional support has a role, always remedying the metabolic response to inflammation and attempting to modify it. For this reason, nutritional support plays an undisputed part in the treatment of such patients. This nutritional support, so necessary in situations with a high degree of stress, must be individually tailored in terms of quantity and quality to the process and to the patient in question. Thus, adapting the support to requirements appears as a priority of nutritional assessment. While it is important to provide nourishment to needy patients, it is just as important if not more so to avoid over nourishment. Indirect calorimetry continues to be the most accurate indicator for determining the needs of each patient and, in view of the lack of knowledge of this technique mainly as a result of economic factors, many different methods and formulas have been proposed to attempt to carry out these adjustments. The characteristics and distribution of the macronutrients will be connected with the pathologies to be treated. And finally, the route for providing this nourishment seems ever more clearly to be as prompt first-line administration through the digestive tube. There are situations in which parenteral support will complement or replace the enteral route when the latter is insufficient or unavailable; in certain circumstances, the parenteral route even seems to be superior to enteral support, as in the case of pure head injury. As these patients are particularly prone to suffer from infections, another aspect of increasing interest in the nutritional support of these patients is the use of immunity-modulating diets, where a better response can be expected. The components of the immunity modulating diets have been shown to be able to modify the immune response in different ways, sometimes favouring the replication of lymphocytes and at other times stimulating the production of certain types of cytokines and attenuating the release of others, in short balancing the inflammatory response. PMID- 11219997 TI - [Nutrition and gene expression]. AB - The genetic information stored in the DNA is transmitted to an RNA molecule through transcription and protein molecules are obtained from the RNA using translation techniques. Each of the processes forming part of this chain is the object of complex regulation (gene expression regulation). Some nutrients may affect gene expression by taking part in these regulatory mechanisms, such as sterols, glucose, vitamins A, D and B12, various fatty acids or some components of dietary fibre. These phenomena may have come about through the adaptation of the primitive beings to the various changes in the nourishment available. The successive changes over centuries have led to the determination of individuals' phenotypes not only by their genotype but also by environmental factors such as diet. Our genes have adapted to the changing sources of nourishment surrounding our ancestors; modern diets are, however, very different from those of the past. The inability of our genetic store to adapt to modern diets may be the reason for the appearance of certain chronic diseases in developed countries. One well analyzed case is that of the thrifty genotype which provided evolutionary advantages in the past, but may now be contributing to obesity and diabetes. Further examples of genotype interaction with various environmental factors to produce different phenotypes are provided by the apolipoproteins: some mutations in the genes of these proteins, in combination with different diet types, are associated with altered lipid levels and the risk of various cardiovascular diseases. These diet-genotype interactions mean that it is fundamentally important to take into account the genetic variability of individuals before recommending dietary measures to prevent the so-called "first-world" diseases. PMID- 11219998 TI - [Nutritional recommendations in gynecology]. AB - In pregnant women, appropriate eating habits has a key role to play in the development of the foetus and is also related with the amount of labour at delivery, helping to avoid complications. In addition, correct nutrition is also necessary during the puerperium to encourage breast feeding and provide the new born child with an adequate nutritional status without leading to any deficits in the mother. PMID- 11220000 TI - [Nutrition and physical exercise]. AB - The principles of a good diet and proper nutrition are the same for people practising sports and for non-athletes. The main difference lies in the amount of energy that sportsmen and women need to carry out a more intense physical activity and to keep an appropriate weight to allow greater performance. The relationship between nutrition and physical exercise has often been shrouded in confusion and conjecture, so certain products or supplements turn into real myths through attempts to achieve better athletic results, despite the fact the information available on the true effect of a particular substance or food on athletic performance is, quite limited and disputed. This paper attempts to clarify the scientific information available on this subject. PMID- 11219999 TI - [Antioxidant micronutrients and human pathology]. AB - The harmful oxidation by free radicals has been implicated in the pathogenesis of many illnesses, including, as the most significant from the epidemiological standpoint, cardiovascular disease and cancer. This paper reviews the physio pathological foundations of this relationship and describes the possible usefulness of anti-oxidant therapy in these and other conditions. PMID- 11220001 TI - [Clinical ethics and nutritional support]. AB - Artificial nutrition is a modern technique enjoying a great boom of late. Regulations on the use of important clinical and technological advances in connection with nutritional support in certain groups of patients represent one of the ethical problems most often posed in daily medical practice. Terminal patient and those with irreversible neurological damage are population groups at risk of these ethical problems when it comes to the prescription, withdrawal or omission of artificial nourishment and hydration. The establishment of certain guidelines in order to resolve the ethical problems arising seems to be a complex process. So far, no consensus has been reached among doctors, with no clear legal framework and no universally accepted ethical principles. It is necessary to ensure the consideration of all the circumstances and parties coming into conflict in order to find the best solution for all concerned by means of shared decision-making. PMID- 11220002 TI - [Oral nutritional supplements. Are they useful?]. AB - Oral nutritional supplements are products included in enteral nutrition, preferably used in hospital settings, although their use in the community is gradually increasing and in the United Kingdom has doubled in the last seven years, with prescriptions covering a wide range of the population from children to the elderly, and different pathologies affecting their nutritional status. There is, however, no consensus on the usefulness of oral nutritional supplements among these patients, so we do not have any recommendations for use. In this paper we have reviewed the various studies available in the literature in order to clarify the usefulness of these supplements in different contexts or pathologies. PMID- 11220003 TI - [Dietetics principles. The food pyramid. Disease-nutrition relationship]. AB - Dietetics is a largely unknown discipline among medical professionals as it is not common for them to receive any training in the matter. Nonetheless, this group very often needs to give dietary counselling and even to draw up diets for patients, more often indeed than nutrition specialists. This paper attempts to review some of the basic concepts of dietetics and study in a general way the relationship between illness and nutritional status without going into too much detail as many of the points mentioned here are referred to more fully in other articles in the same monograph. PMID- 11220004 TI - [Diabetes and nutrition]. AB - Diabetes mellitus is one of the most frequent metabolic syndromes found in our hospitals, occurring at around 10%. There are basically two types: the most common is Type 2, associated with obesity in almost 80% of cases and family groupings, and then, far behind, comes Type 1 which requires insulin administration for life. Furthermore, there is a condition known as "stress hyperglycaemia" in which a patient without a prior history of diabetes mellitus responds to stress with a syndrome comprising hypermetabolism, hyperglycaemia, hyperlactacidaemia and protein catabolism. The desirable pre-prandial levels of glycaemia in an outpatient are between 80 and 120 mg/dl (under 100 mg/dl is normal) and between 100 and 140 mg/dl before retiring (levels of 110 mg/dl are normal). In patients with artificial nutrition, whether parenteral or enteral, the control of glycaemia is not so strict and the recommendation is for a level of around 150-200 mg/dl in the acute stress phases, falling to 100-150 mg/dl in stable patients. The ideal enteral formula for diabetic patients has been a bone of contention for years and has still not been satisfactorily resolved. The discussion centres on the replacement of saturated fatty acids by mono unsaturated fatty acids (MUFA) or by carbohydrates. The studies of patients undergoing prolonged treatments with MUFA-rich enteral diets have shown a greater control of glycaemia with these diets than with those rich in carbohydrates, so Type 2 diabetics and in stress hyperglycaemia with enteral nutrition, there is an ever stronger proposal to use MUFA rich formulas, whereas in Type 1 diabetics and in Type 2 patients with high prior requirements of insulin, it would be more recommendable to use diets with a more intermediate composition. With regard to parenteral nutrition, there is a consensus on increasing the amount of fatty acids to the detriment of carbohydrates, but the use of carbohydrates other than glucose is not so clear. The use of fast-acting insulin, either intravenously or subcutaneously, is recommended in the acute stages of the underlying condition because any instability in the patient makes it difficult to plan the required dose of intermediate-acting NPH insulin. The use of metformin or acarbose is not recommended. In parenteral nutrition, the subcutaneous administration of NPH insulin is often required at doses of 30% of the home dosage as the basal insulin therapy in addition to fast-acting insulin in the nutrition bag and a regimen of subcutaneous fast-acting insulin every 6 hours depending on glycaemia. PMID- 11220005 TI - [New nutrients in enteral nutrition]. AB - 1. Medical and surgical stress (major surgery, sepsis, injuries,...) increases requirements of certain essential nutrients and others considered non-essential or semi-essential. 2. Some nutrients such as glutamine, arginine, omega 3 fatty acids nucleotides, ... have a considerable influence on the immune function (delayed hypersensitivity, lymphocyte sub-population counts, immunological tests,..) and improve certain metabolic and nutritional indices (nitrogen balance, medium and short life proteins,...). For this reason, they are called "immunonutrients" or "immunity regulators". 3. The supply of special enteral formulas for situations of immunological compromise, with the addition of one or more of the nutrients considered today as "immunity regulators" has increased since 1988 in both absolute and percentage terms. 4. These nutrient-enriched enteral formulas improve the rate of infections, reduce the number of days on ventilator equipment, the length of hospital stays for critical patients, with a more marked effect on surgical patients. 5. The evidence seems today to support the use of enriched formulas with critical patients. Nonetheless, some caution must be maintained as it has not been possible to show any reduction in the mortality of the cases studied nor, in short, in the prognosis of patients affected by situations of hypercatabolism and reduced immunity. 6. We feel that their use should, therefore, be carried out in accordance with the protocols and in patients expected to survive, where the evolution reveals severe catabolism unhindered by conventional therapy. PMID- 11220006 TI - [Early enteral nutrition and immunonutrition]. AB - The repercussions of nutrition on the immunological system are described. The current situation is discussed with regard to the handling of the immuno inflammatory response to aggression and the improvement of the immune response. The goal pursued by nutritional manipulation of the immune system is to improve the prognosis and reduce the complications in critical patients subjected to surgical or traumatic aggression or sepsis. The following points are reviewed: the importance of preserving the axis from the liver to the digestive tract, the advantages of particularly early enteral nutrition over parenteral nutrition, the substances currently considered as immunonutrients and the available clinical evidence on their use, with a series of conclusions for current decisions and future developments. PMID- 11220007 TI - [Nutritional support in pancreatitis]. AB - Pancreatitis is an illness that can bring about nutritional changes in connection with the underlying cause, the metabolic reaction to stress or the limitations that this pathology may represent for the processes of digesting and absorbing nutrients or for tolerating the diet. Although nutritional support is well accepted as a therapeutic measure in patients with severe acute pancreatitis, there is some dispute over the route of administration. In patients with mild pancreatitis, the use of parenteral nutrition may be accompanied by an increase in complications, particularly due to catheter-related sepsis, but in severe cases, early parenteral nutrition has been associated with a lower incidence of complications and a drop in mortality. Although parenteral nutrition is the preferred conventional method for the nutritional support of patients with pancreatitis, enteral nutrition offers the advantages of being more physiological, safer and less costly, at the same time as it seems to have a favourable influence on the progress of the pancreatitis. For this reason, the current recommendations suggest the use of enteral nutrition via the jejunum in those cases where the severity of the pancreatitis indicates nutritional support. Further research is, however, necessary in this field to clarify the group of patients in which the benefits of nutritional support would be most evident, the most appropriate type of diet, and the role of enteral nutrition on the evolution, both locally and systemically, of the changes brought about by the inflammation of the pancreas. PMID- 11220008 TI - [Nutrition and respiratory insufficiency]. AB - Unlike other pathologies, not much attention has been paid to the relationship between nutrition and respiratory disease. This is probably because some of these diseases, such as cancer and chronic obstructive pulmonary disease, are closely associated with smoking while others that could be more directly linked with nutrition such as cystic fibrosis and emphysema are not directly caused by nutrition disorders. Not all patients with chronic obstructive pulmonary disease are undernourished. When malnutrition is present in these patients it is because of multiple reasons and is associated with an increase in both mortality and morbidity. In patients with acute respiratory insufficiency, malnutrition is often secondary to a heightened catabolic state leading to the severe fundamental illness. We also know that nutritional treatment may not only correct malnutrition but also help in improving the respiratory function. This nutritional therapy is not normally easy to comply with. It must be accompanied by other non-pharmacological therapies such as rehabilitation. Renourishment may also entail risks for patients with respiratory diseases so it is very important to know as closely as possible their nutritional requirements and to focus on specific actions. PMID- 11220009 TI - Casebook: microscopic haematuria. PMID- 11220011 TI - The kidney in hypertension. PMID- 11220012 TI - The orals--a chance to make the right impression. PMID- 11220013 TI - The challenge of finding donors. PMID- 11220010 TI - Dialysis patients: the GP's role. PMID- 11220014 TI - A homeless teenager who may be pregnant. PMID- 11220015 TI - Homeopathy: let likes be cured by likes, Part II. PMID- 11220016 TI - Urinary incontinence in women: assessment and management in the primary care setting. AB - Urinary incontinence, the unwanted loss of urine, is a condition that affects millions of women and yet is often not addressed by the primary care provider. The unfortunate consequence of this ignorance is that, if correctly diagnosed and managed 80% of these patients could have marked improvement in clinical symptoms. The intent of this report is to familiarize the reader with a systematic approach to the assessment, diagnosis, and management strategies for urinary incontinence in the outpatient setting. PMID- 11220018 TI - Mastalgia: evaluation and management. AB - Mastalgia, defined as breast pain, is a common, often distressing complaint among women. It is the most common breast-related complaint in primary care clinics, with a prevalence in working women of approximately 66%. An underlying fear of breast cancer is what prompts these patients to seek health care. A comprehensive history and thorough clinical breast exam is essential to evaluation. Once significant breast disease is ruled out, the majority of these patients respond to simple reassurance. PMID- 11220017 TI - A case study approach to evaluation of cardiac disease in women. AB - Women rarely consider coronary heart disease as a health concern despite the fact that it is the leading cause of death in women in the United States. We have just recently begun to appreciate the gender and age differences related to coronary heart disease presentation and management in women. Management challenges often relate to the unusual or atypical disease presentation and course, and are frequently misunderstood by the practicing clinician. Comorbidities and prevention strategies in the female patient must be carefully considered. Early risk reduction and counseling should be incorporated into every well-woman exam so that women receive the timely and appropriate care they need and deserve. PMID- 11220019 TI - Decreased libido in postmenopausal women. AB - As baby boomers age, the health issues of postmenopausal women have gained increasing media attention. Sexual well-being is an important health component for these women. The estimated rate of female sexual dysfunction in the United States is an astounding 25% to 63% with the most prevalent age group being postmenopausal women. Decreased libido is a major complaint of postmenopausal women, and many seek medical consultation for this problem. Unfortunately, current female sexuality research for this population is clearly deficient. Additionally, medical providers tasked with managing postmenopausal sexual dysfunction often lack training, experience, and the confidence necessary to handle sexuality concerns. Nurse practitioners, as superior counselors, are in a prime role to address this issue. The purpose of this report is to focus on the multifaceted problem of decreased libido in postmenopausal women, with management strategies to assist practitioners in managing and addressing this problem in the clinical setting. The report will investigate several physical, hormonal, and psychosocial factors impacting decreased libido in these women. Current and past research into this area will be analyzed to better define the current professional consensus on managing decreased libido in postmenopausal women. PMID- 11220020 TI - Hormone replacement therapy. AB - By the year 2020, more than 45 million American women will be over the age of 50. Many of these women will wrestle with decisions concerning the use of hormone replacement therapy. This report presents a history of hormone replacement therapy use. The report then addresses the benefits, risks, and relative and absolute contraindications associated with hormone therapy. Concluding sections of the report discuss hormone replacement options which are currently available as well as provider considerations when tailoring a therapy regimen to the needs of the patient. PMID- 11220021 TI - Clinical challenges in menopausal management: a case study approach. AB - Selecting an appropriate hormone replacement regimen can pose many challenges to the clinician and the patient. This report offers 4 case studies and clinical considerations illustrating both scientific and clinical considerations when collaborating with women to find an acceptable method to manage menopausal symptoms. Both traditional and complementary therapies are considered. PMID- 11220022 TI - Travel and expatriate health: an overview. PMID- 11220023 TI - Recent trends in infectious diseases for travellers. AB - In the early 1970s medicine was considered to have conquered infectious diseases. The following three decades have shown this optimism to be misplaced, with both traditional infections increasing in prevalence and novel diseases appearing. Many of these diseases have become major problems in developing countries, and coupled with the exponential growth in international traffic now pose a significant risk to the traveller. The threat to the package tourist differs greatly from that to the businessman, soldier or backpacker. The latter groups may have little control over their food and water supplies and be exposed to vector-borne and zoonotic infections normally restricted to remote locations. However the package holidaymaker may be involved in mass outbreaks of food poisoning with novel pathogens or acquire unusual infections from close proximity to other tourists. All groups may be susceptible to diseases transmitted during travel, and these may be more common than is presently recognised. The common factor is that all such infections may be transported around the world within their incubation period, and that any disease can now present to any doctor. Today more than ever before it is incumbent on any practitioner to ask not only 'where have you been?' but also 'what were you doing there?' PMID- 11220024 TI - The assessment of fitness to travel. AB - The majority of health problems encountered in association with travel stem from pre-existing, perhaps latent, illness in the individual which may be exacerbated by the rigours and hazards of travel. It is essential that the advising physician understands the hazards that are likely to be encountered during travel in order that they may develop informed decisions regarding fitness for travel and give appropriate advice. In an occupational health setting, the employer has a responsibility to safeguard the health of their employees whilst travelling on behalf of the organisation and will also have to fund any treatment abroad or the cost of repatriation. The dictating factor in determining fitness to travel will often be fitness to travel by air, consequent to the reduced partial pressure of oxygen and pressure changes in-flight. The majority of significant health problems encountered during travel are attributable to coronary heart disease and detailed guidance exists to determine fitness for travel. For many health problems little if any evidence based guidance exists and decisions will therefore have to be based on an understanding of the hazards likely to be encountered during travel. Access to appropriate standards of medical care abroad and the difficulties and expense of repatriation, should this be necessary, are also important factors to consider in addition to the basic determination of fitness for travel itself. This paper outlines the main factors to be considered when assessing fitness to travel and also examines available guidance for some of the more commonly encountered conditions. PMID- 11220025 TI - Medical aspects of expatriate health: health threats. AB - The globalisation of business activity can lead to the movement of key employees and their dependants from country to country. In their host country these expatriates often face health hazards not experienced at home. This paper describes the range of health issues of relevance to expatriates. PMID- 11220026 TI - Medical aspects of expatriate health. PMID- 11220027 TI - Assessment of the returned traveller. AB - The occupational health physician is in a unique position to provide total care for the returned traveller. In a sense, the physician packs and unpacks with the patient and ensures that other carers consider a wider range of disease possibilities than may be found in the home country. Follow-up tests and examinations are comparatively simple and where necessary specialist advice should be sought. PMID- 11220028 TI - Occupational respiratory symptoms in New Zealand hairdressers. AB - BACKGROUND: A study of occupational respiratory symptoms in hairdressers was carried out in 26 salons in New Zealand. METHODS: A questionnaire was administered to 100 hairdressers and 106 office and shop workers, recording respiratory symptoms, demographic data, and smoking habits. Pulmonary function was measured before each shift. RESULTS: Hairdressers had a higher prevalence of asthma symptoms, diagnosed asthma, and asthma attacks in the previous 12 months, but these differences reduced markedly when adjusted for age, gender and smoking. Hairdressers had a significantly lower pulmonary function, even after adjustment for smoking, but this difference was entirely due to differences between hairdressers and office workers and there were no such differences between hairdressers and shop workers. CONCLUSIONS: The excess symptom prevalence in hairdressers was largely due to the high smoking rates. Mean pulmonary function was lower in hairdressers but this finding requires further study. PMID- 11220030 TI - Occupational skin conditions in the food industry. AB - The study presents the findings of a questionnaire survey of skin conditions in a selective sample of the UK food industry, covering companies who employ occupational physicians. The mean incidence of skin conditions in food manufacturing operations was 2103 per million employees per annum. The mean incidence in retail or catering organizations was 1414 per million employees per annum. PMID- 11220029 TI - Psychological and occupational predictive factors for back pain among employees of a university hospital in southern Spain. AB - OBJECTIVES: To identify the individual and occupational factors that are predictors for low back pain among the employees of a university hospital in southern Spain. METHODS: A transverse study was conducted in which the population used was the hospital employees who volunteered to participate. The information was obtained by using a questionnaire, which included demographic and anthropometric variables, habits, characteristics of the work done, and of any pain experienced. The mental health condition of subjects was measured using the GHQ-28, using a score of > or = 6 as the cut-off point. To study the variables associated with pain, crude odds ratios (ORs) were calculated (+/- 95% CI) and adjusted according to a logistic regression model. RESULTS: One thousand one hundred and four subjects participated in the study but only 890 of these completed the questionnaire in full (rate of response, 35.7% of total employees). The population studied was notable for the high proportion of women, for subjects > 41 years of age, and subjects who undertook little or no physical exercise. In addition, according to the GHQ-28 test, 29.9% of the total were 'probable psychiatric cases'. The crude ORs were high in all the occupational categories in comparison with the doctors, with the exception of the maintenance, cleaning, and catering group. They were also higher among women, among subjects with poor mental health, and among women with one or more children. The adjusted ORs showed that having a GHQ-28 score of > or = 6, and belonging to the auxiliary technician category, were independent risk factors for suffering low back pain. Being older than 41 years and in temporary employment were protective variables. CONCLUSIONS: The presence of probable mental illness is the variable most strongly associated with the presence of low back pain in the population studied. Its diagnostic confirmation and appropriate treatment could contribute to reducing the prevalence of vertebral pains in this occupational group. PMID- 11220031 TI - An investigation of the validity of 'simulated' work related tasks in relation to 'real-life' situations in the fire service training environment. AB - Many researchers have developed work simulated tasks that can successfully predict fitness for work. In the fire service there are few tests available to make such predictions. This study was designed to evaluate the validity of four simulated fire-fighting tasks developed by Manchester Fire Service. Twenty-seven subjects each performed, in random order, three repeats of four simulated and four real-life tasks: under-running a 9 m ladder, dead lift, placing a 13.5 m ladder on an appliance and hauling an extended line. Comparisons between real and simulated tasks were assessed by measuring total time and amount of muscle activity. Recommendations were made to reduce the weight and to revise the lifting and grip positions for the 13.5 m ladder and dead lift, respectively, whereas the simulated 9 m ladder and hauling an extended line simulated tasks were sufficiently similar to the real-life activities to not warrant any change. PMID- 11220032 TI - Gender differences in musculoskeletal health of computer and mouse users in the Swedish workforce. AB - The objectives of the study were to explore the musculoskeletal health of computer users in the Swedish workforce with regard to gender and psychosocial factors, and to describe gender differences between the occupational groups. A subset was chosen from a large survey of 12,462 individuals representing the workforce of Sweden, performed by Statistics Sweden. Included in the subset were 2044 subjects who worked for at least half their working hours with personal computers, or an equivalent device, and also used a computer mouse. All occupational groups had prevalence ratios (women/men) > 1. When using regression models, the variables 'learn and develop' and 'involved in planning your work' were health factors, and 'too much to do' was a risk factor for upper body symptoms for both women and men. For women 'PC duration 100' was a risk factor and 'support from superiors' was a health factor. Age seemed to be a stronger risk factor for men than for women. PMID- 11220033 TI - The prevention of tuberculosis in prison staff. AB - The Joint Tuberculosis Committee of the British Thoracic Society (BTS) recommends that all new prison staff be screened for tuberculosis (TB) as 'at risk' health workers. This study of prisons in the West Midlands area of England shows that there are considerable variations in the practice of TB control amongst prison staff and that the recommendations of the BTS committee are not routinely implemented. The study highlights the need for a routine and robust system of TB surveillance and prevention amongst prison staff which can be applied nationwide. PMID- 11220034 TI - Effects of exposure to very high frequency radiation on six engineers in two separate incidents. PMID- 11220035 TI - How do you manage dermatitis after exposure to the causative agent has ceased. PMID- 11220036 TI - The influences of stimulus wavelength and eccentricity on short-wavelength pathway isolation in automated perimetry. AB - The aim of the study was to determine whether the suggested stimulus and background parameters employed in commercially available short-wavelength sensitive perimetry (SWAP) are clinically appropriate. Threshold versus intensity curves were measured using a modified Humphrey Field Analyser. The reduction in background luminance was achieved using aperture stops in order to avoid changes in the chromaticity of the background. Short-wavelength thresholds were determined for 440, 450 and 460 nm stimuli and were corrected for pre-receptoral absorption. Short-wavelength sensitive pathway isolation was approximately 1.5 log units and decreased with increases in eccentricity and in stimulus wavelength. It would seem that the use of a 450 nm narrowband stimulus filter would offer a compromise between both the physiological requirements and the physical properties of the stimulus. Such an approach would reduce some of the inherent between-subject normal variability associated with SWAP. PMID- 11220037 TI - Validation of grading scales for contact lens complications. AB - The validity of use of two artist-rendered and two photographic sets of grading scales (grading 'systems') designed for gauging the severity of contact lens related ocular pathology was assessed in terms of precision and reliability. Thirteen observers each graded 30 images--by interpolation or extrapolation to the nearest 0.1 increment--of each of the three contact lens complications (corneal staining, conjunctival redness and papillary conjunctivitis) that were common to all four grading systems. This entire procedure was repeated approximately two weeks later, yielding a total data base comprising of 9360 individual grading estimates. Analysis of variance revealed statistically significant differences in both precision and reliability between systems, observers and conditions (p < 0.03 for system reliability; p = 0.0001 for all other combinations). The artist-rendered systems generally afforded lower grading estimates and better grading reliability than the photographic systems. Corneal staining could be graded less reliably than conjunctival redness and papillary conjunctivitis. Grading reliability was generally unaffected by the severity of the condition being assessed. Notwithstanding the above differences, all four grading systems are validated for clinical use and practitioners can initially expect to use these systems with average 95% confidence limits of +/- 1.2 grading scale units (observer range +/- 0.7 to +/- 2.5 grading scale units). In view of the significant between-system differences revealed in this study, it is advisable to consistently use the same grading system. It may be possible to reduce between-observer differences by applying personalised correction factors to normalise grading estimates. PMID- 11220038 TI - Clinical grading of corneal staining of non-contact lens wearers. AB - To distinguish normal from pathological corneal fluorescein staining requires knowledge of background levels of staining among otherwise healthy individuals. Corneal staining of 102 non-contact lens wearing subjects was assessed using a photographic grading scale that uses a generic (0 to 4) scale to score corneal staining. Some degree of corneal staining was found on 79% of the corneas. Low inter-observer variability suggests that the corneal staining grading scale can be used successfully with decimal rather than integer scale increments. PMID- 11220040 TI - Why do we still not know whether refractive error causes headaches? Towards a framework for evidence based practice. AB - In this paper, we systematically review the available experimental and clinical evidence concerning the causation of headache by refractive error. Despite the apparent belief of both medical and optometric professionals that provision of an appropriate correction may alleviate various types of headache, there is little if any robust evidence in support of this position. We identify four serious methodological and theoretical difficulties with studies to date, which currently render it impossible to assess the relationship between refractive error and headache. The provision by the International Headache Society of the diagnostic category "headache associated with refractive error" is called into question. Five research questions are posited in the form of a framework for the development of evidence-based practice in optometry and the treatment of headache. PMID- 11220039 TI - Randomised controlled trial of an integrated versus an optometric low vision rehabilitation service for patients with age-related macular degeneration: study design and methodology. AB - A number of studies have measured the outcomes of low vision care but these have usually been longitudinal case series, thus constituting very low quality of evidence for effectiveness. To date, there have been no randomised controlled trials (RCTs) which have evaluated the effectiveness and cost effectiveness of different models of care in low vision. The size of the low vision population and the paucity of systematic evaluation have created a pressing need for evidence about cost-effectiveness in order to inform service developments for low vision rehabilitation. This paper describes the study design and methodology of a three arm RCT currently under way in Manchester. The baseline population recruited is also described. A traditional hospital-based optometric service is being compared with an integrated service (comprising the addition of community-based rehabilitation officer input) and with more generic community input (which is non integrated and is not vision specific). A wide range of outcome measures are being assessed at recruitment and 12 months post-intervention, including low vision specific and generic quality of life measures, patterns of low vision aid use, and task performance. The rationale for the trial is discussed and the main study outcomes are described. PMID- 11220041 TI - Analysis of discrimination threshold on the tritan axis. AB - Discrimination thresholds on the tritan axis were obtained for an extensive group of 66 stimuli: in some of the stimuli, S-cone trolands were held constant by keeping the product of the S-cone excitation level and the luminance unchanged, while in others only the luminance was changed to establish various S-cone troland values. These thresholds depended clearly on the S-cone value of the stimuli, while they remained almost constant against the retinal illumination. Thus, we noted that the excitation of the L - 2M channel had practically no influence over the discrimination threshold on the tritan axis, although this independence of delta S from L - 2M was not so obvious when the S value was high. With our data, we performed different fits, and found that the fit including the terms S, (L - 2M) and (L + M) adapted better to our results. PMID- 11220042 TI - General binocular disorders: prevalence in a clinic population. AB - The purpose of this paper was to study the prevalence of nonstrabismic accommodative and binocular dysfunctions in a clinical population. We examined 265 symptomatic patients who were chosen from an optometric clinic. We performed several tests to diagnose any form of refractive, accommodative or binocular dysfunction. Of the 265 subjects examined, 59 patients (22.3%) had some form of accommodative or binocular dysfunction and required not just the correction of the refractive error but a specific treatment for each of the problems diagnosed. The remaining subjects were classed as having refractive anomalies. The frequency of binocular dysfunctions was 12.9%, and 9.4% for accommodative anomalies. Convergence excess (4.5%) was more prevalent than convergence insufficiency (0.8%) and accommodative excess (6.4%) more prevalent than accommodative insufficiency (3%). PMID- 11220043 TI - Nearwork distances in children. PMID- 11220044 TI - Changes in the static accommodation response with age. AB - A transverse study of the monocular, steady-state accommodation response/stimulus curves for 49 normal subjects with ages between 17 and 49 years shows that the slope of the curve reduces only slowly with age up to about 40 years and then declines rapidly as complete presbyopia is approached. Such behaviour appears to result from the accommodation system changing its characteristics with age to make optimal use of the available objective amplitude of accommodation and the depth-of-focus of the eye. PMID- 11220045 TI - Effect of oral contraceptives on tear physiology. AB - Variations in sex hormones due to the menstrual cycle (and oral contraceptives) were evaluated for their effect on tear physiology. Subjects were 18 females taking oral contraceptives or their age matched controls (no medication), aged 21 33 years. Symptoms of ocular discomfort (visual analog scale), tear film structure (TearScope), non-invasive tear thinning time (HirCal grid), evaporation rate (ServoMed evaporimeter), osmolality (Nanolitre Osmometer), tear turnover rate, tear volume (Fluorotron Master), and tear protein levels (HPLC) were measured around day 2 (D2), actually day 1-4 and day 19 (D19) actually day 18-21 of the cycle. No significant differences were found for any tear parameters between D2 and D19 for either pill users or controls alone, or in the comparison of pill users with controls. No effect on tear physiology was found for serum hormone changes induced by oral contraceptive use or by normal cyclic variations in healthy young females. PMID- 11220046 TI - Homeopathy: let likes be cured by likes. PMID- 11220047 TI - First pelvic examination in the adolescent. AB - The first pelvic examination is often an emotionally charged and stressful event in the adolescent patient. The female adolescent patient has many unique health care needs, which if not met, can negatively impact future gynecologic health. History taking and physical examination techniques specific to the adolescent female patient are discussed. Indications for pelvic examination along with practice tips in communicating with the adolescent female patient are reviewed. Methods of reducing patient anxiety and empowering the adolescent to take charge of her health are discussed. PMID- 11220048 TI - Exploration of facilitators and barriers to prenatal care among military women. AB - Early and regular prenatal care has been shown to decrease the incidence of adverse pregnancy outcomes; however, little research has examined it experientially from the mother's perspective. The purpose of this qualitative study was to explore the experience of prenatal care from the military mother's perspective. Using purposive sampling, 16 women who had recently given birth were interviewed. The data were analyzed using a qualitative descriptive research methodology to elicit categories of substantive concepts, ideas, or themes. Data explored in this study included availability, use and satisfaction with prenatal care services, and barriers, preferences, and recommendations. PMID- 11220049 TI - Major depressive illness in women: assessment and treatment in the primary care setting. AB - Depressive illness in women carries with it a tremendous price to the woman's sense of well-being and health. Primary care providers who have frequent and continuous contact with women at risk for developing a depressive disorder are in an excellent position to diagnose and treat depression. PMID- 11220050 TI - Smoking cessation and low-income women: theory, research, and interventions. AB - There is a growing body of evidence indicating women's experiences with smoking and cessation may be unique from those of men. Advanced practice nurses (APNs) in primary care are ideally suited to assess and intervene with this complex addiction. APNs must be competent in interventions that address cigarette smoking. This article will summarize the literature on smoking cessation interventions with an emphasis on women smokers. PMID- 11220051 TI - HIV risk reduction strategies for low-income African American women. AB - Intervention strategies from the Health Education Reaching Out into the Community project that can be used in the clinical setting to assist low-income African American women adopt sexual behavior that is low risk for human immunodeficiency virus are discussed. These strategies include allocation of adequate time, the nurse practitioner's acceptance of the client, the use of adult learning principles, and active client participation through discussion, return demonstration, role play, and promotion of the client's ownership of the information learned. PMID- 11220052 TI - Physical activity stages of change in African American women: implications for nurse practitioners. AB - We examined stages of change in the physical activity in African American women aged 17 to 64 years (N = 104) who obtain primary health care. Forty-seven percent of the women had at least 1 chronic health problem that required treatment. Overweight or obesity was found in 66% of the women. The majority of women were in the precontemplation (21%) and contemplation (19%) stages of change; 27% were preparing to become active. Forty percent were classified as very low active; 34%, low active; and only 26% were moderate or high active. Simple logistic regressions showed that women who were inactive during adolescence were 6 times more likely than other women to be in an early stage of change in physical activity (precontemplation or contemplation stage). Women who were self-motivated to be physically active, had support of friends and family, and enjoyed physical activity were more likely than other women to be in maintenance stage of activity. This article provides information on ways to use the stages of change and associated factors to move patients from inactivity to activity and help them remain active in the long term. PMID- 11220053 TI - Preventing injuries to infants of adolescent mothers. AB - Infant injury prevention is an important issue for practitioners who work with adolescent mothers. Data are presented to examine the association between having a young mother and being injured as an infant. Prevention messages need to take into account that parents in general tend to minimize the magnitude of injury risk to their children. With careful documentation, using External Cause of Injury Codes, practitioners may be able to estimate the cost savings of prevention initiatives. PMID- 11220054 TI - Discipline across generations. AB - The objective of this qualitative research was to understand how parents decide which discipline practices they will repeat from their childhoods. Participants chose not to repeat punishment practices when a strong, negative effect was remembered. However, some parents repeated physical punishment practices even when a strong, negative effect was remembered if they believed the practices were effective or culturally valued, if they were under stress, or if the parents lacked alternative strategies. PMID- 11220055 TI - Cardiovascular risk among middle school children: implications for primary care. AB - Cardiovascular risk reduction programs for school-aged children are based primarily in schools. Primary care providers, however, have not routinely included active cardiovascular risk reduction efforts in their practice. The research reported here supplies providers with evidence that can readily guide interventions augmenting cardiovascular risk reduction information and skills that children may be learning in schools. PMID- 11220056 TI - Cost analysis: a tool for measuring the value of nurse practitioner practice. AB - The survival of nurse-managed centers and their ability to provide practice opportunities for advanced practice nurses depends on combining sound business practices and active financial management with clinical excellence. Using cost analysis methodologies, this study examined the operational costs of 2 academic based nursing centers and analyzed the practices that resulted in profitability for 1 and questionable survival for the other. PMID- 11220057 TI - Peripheral neuropathy: alternative and complementary options. PMID- 11220058 TI - More than personal change: effective elements of symptom management. AB - Symptoms are the most common reason people seek health care. Although the menstrual cycle, a normative process, is not a chronic illness, about 10% to 15% of women experience severe recurring symptoms associated with the menstrual cycle that can be considered a chronic illness. Severe perimenstrual symptoms, although distressing for some women, provide a model for understanding complex gender specific conditions that include biological, psychosocial, and cultural factors, and have application to other women's health problems such as stress-related conditions (heart disease, arthritis, immune system disorders), psychiatric disorders, or normative menstrual cycle transitions (menarche, postpartum, menopause). The Perimenstrual Symptom Management Program, developed by the author, was evaluated to determine the short-term and long-term effectiveness of a multimodal, nonpharmacological treatment package aimed at relieving the symptom and stress experience as well as increasing health behaviors. Selected results from this longitudinal clinical trial will be presented along with examples of effective elements of personal and environmental strategies for symptom management and health promotion. Recommendations for clinical application of these research findings will be presented with a focus on both patient outcomes and intervention processes for personal and environmental therapeutic change. PMID- 11220059 TI - Herbal remedies: efficacy in controlling sleepiness and promoting sleep. AB - Difficulties with sleep and daytime sleepiness are common complaints among adults in the United States. During the past decade, the use of herbal preparations among adults increased from 2.5% to 12.4%. This article presents relevant aspects of the 1994 Dietary Supplements Health and Education Act that stimulated the proliferation of herbal medicinals and reviews the pharmacological properties of the most commonly available herbal wake-promoting and sedating products. Given the rapid increase in use of herbals, health care professionals need to educate themselves and their patients about the use of these preparations. PMID- 11220060 TI - Homocysteine--a novel risk factor for vascular disease. PMID- 11220061 TI - Continuous fetal heart rate monitoring: is there a conflict between confidential enquiry findings and results of randomized trials? PMID- 11220062 TI - Strong opioids for cancer pain. PMID- 11220063 TI - Screening for lung cancer. PMID- 11220064 TI - Instrumental psychosis: the Good Soldier Svejk syndrome. AB - The possession of severe mental illness, mainly schizophrenia and affective psychosis, may be perceived in positive terms. We have identified a group of patients, most of them with a history of previous psychotic disorder, who present with deliberately created symptoms and behaviour, and who are defined as having instrumental psychosis. Because most such patients have had a psychotic disorder in the past the symptoms are very like those of a real psychosis. A parallel is drawn with the fictional anti-hero of the Czech nation, the Good Soldier Svejk, who demonstrated both real and instrumental psychosis. A rating scale, the 'pseudopsychosis inventory', was devised to identify the main components of this disorder and was applied in 15 consecutive patients presenting with putative psychotic disorders in whom assessment could be made by two raters within five days. The inter-rater reliability of the items of the scale was good (intra-class correlation coefficient 0.68). An epidemiological study with this scale in 45 patients with a putative psychotic disorder suggested the presence of instrumental psychosis in 2. PMID- 11220065 TI - Recovery from chronic fatigue syndrome associated with changes in neuroendocrine function. PMID- 11220066 TI - Vascular Ehlers-Danlos syndrome undiagnosed during life. PMID- 11220067 TI - Acute abdomen after cardiac surgery: three cases, one fatal. PMID- 11220068 TI - Remission of precapillary pulmonary hypertension in systemic lupus erythematosus. PMID- 11220070 TI - Common iliac aneurysm rupture with sinus bradycardia. PMID- 11220069 TI - Sarcomatoid renal cell carcinoma metastatic to right ventricle. PMID- 11220071 TI - Subclinical presentation of massive retropharyngeal abscess. PMID- 11220073 TI - John Hunter's teachings on gunshot wounds. PMID- 11220072 TI - Leechcraft in nineteenth century British medicine. PMID- 11220074 TI - Expedition health and safety. PMID- 11220075 TI - Why doctors get angry in Crown courts. PMID- 11220076 TI - Reversible dementia in Paget's disease. PMID- 11220077 TI - Management of colorectal liver metastases. PMID- 11220078 TI - Knowledge and the Internet. PMID- 11220079 TI - Research as part of routine care. PMID- 11220080 TI - Management of explicit and tacit knowledge. PMID- 11220081 TI - [Homocysteine, endothelial dysfunction and cardiovascular risk: pathomechanisms and therapeutic options]. AB - Elevated homocyst(e)ine plasma concentrations are an independent risk factor for cardiovascular disease. Hyperhomocyst(e)inaemia is common in patients with peripheral arterial occlusive disease, coronary heart disease, cerebrovascular disease, carotid artery stenosis and venous thromboembolism. Endothelial dysfunction may be one underlying cause leading to proatherogenic effects associated with hyperhomocyst(e)inaemia. However, the mechanisms which lead to impaired endothelial function in hyperhomocyst(e)inaemia are not fully understood. Recent evidence suggests that homocyst(e)ine may interact with physiological mediators of the endothelial matrix. Oxidative mechanisms and decreased biological activity of endothelium-derived nitric oxide (NO) may also contribute to homocyst(e)ine-associated endothelial dysfunction. B vitamins are essential cofactors in the metabolism of homocyst(e)ine to methionine via the remethylation-pathway (vitamin B12, folic acid) and to cystathionine via the transsulphuration-pathway (vitamin B6). Dietary deficiencies of folic acid, vitamin B12, and vitamin B6 appear to be common among elderly people in the western world and represent one pathogenic factor related to the incidence of hyperhomocyst(e)inaemia. Several studies have demonstrated that dietary supplementation with folic acid and the vitamins B12 and B6 is an efficient means to decrease plasma homocyst(e)ine. No clinical studies are available to date to prove whether reducing homocyst(e)ine levels to the normal range by supplementary B vitamins will also beneficially affect vascular function or cardiovascular risk. Furthermore it is unknown whether moderately elevated homocyst(e)ine concentrations per se may predispose to development of vascular disease, or whether homocyst(e)ine is an indirect marker of cardiovascular disease. Further investigations will be necessary to elucidate the causal relationship between elevated homocyst(e)ine plasma concentrations and the incidence of cardiovascular events, especially since the therapeutic strategies in hyperhomocyst(e)inaemia would differ depending on the underlying pathophysiological mechanisms. PMID- 11220082 TI - [Standardized findings in echocardiography using WWW: EchoBefundSystem]. AB - As a non-invasive imaging system, ultrasound echocardiography has a very high impact on modern diagnosis and is widely used in clinical routine but without any structured and standardized documentation of the results. Thus, quality management (QM), statistics and comparison of the results are difficult. Therefore, a working group of the German Cardiac Society issued a consensus proposal. For evaluation and wide public distribution, we have developed the first internet-based application covering the full proposal: EchoBefundSystem. The EchoBefundSystem is a web based client-server application for standardized documentation of echocardiography results right at the workplace. The software leads the examiner by means of a user interface design and stored medical knowledge. The level of detail is scaled automatically to the ongoing examination. Every day clinical routine is performed on only two pages, one for general patient data and a second one covering the complete minimal data set called "minimum finding" in the standard. As the examiner discovers more and more special findings or might even enter a complete medical study, the interface offers more and more fields and checkboxes. One data set can contain up to 600 values and findings. The structured user interface reflects the organ structure as well as examination methods familiar to the examiner. Automatically calculated fields speed up the examination. Judgements, diagnoses, values and ranges are interrelated. If there is a difference between the entered data and the medical knowledge base, a warning will be issued but the doctor's decision is authoritative. Some values may be gathered by different methods and even different units are converted automatically. The final doctor's letter is generated automatically in clear text but still editable and can be given out to the patient right after the examination without any further delay. Beside the minimal data set, all abnormal findings will appear and findings will be summarized wherever possible. The report is intended for the referring general practitioner, your own documentation, expert witness as well as clinical studies. Interested examiners may test the full version online at http://echo.ma.uni heidelberg.de PMID- 11220083 TI - [Exclusion of coronary calcium with electron beam tomography: an effective filter before invasive diagnosis in symptomatic patients?]. AB - Electron beam computed tomography (EBCT) is the most sensitive and accurate method of measuring coronary calcium which indicates coronary atherosclerosis. We performed a prospective study in 1764 symptomatic patients who were referred to our hospital for coronary angiography because of suspected coronary artery disease. In all of these patients cardiac catheterization and coronary calcium scanning was performed within 3.2 +/- 4 days. 454/1225 men (37.0%) and 165/539 women (30.6%) had significant coronary stenoses > or = 75%. Only two men (0.4%) and no single woman (0.0%) with stenoses > or = 75% and only 3/323 patients (0.9%) with moderate stenoses (50-75%) did not exhibit coronary calcium. Coronary angiography excluded stenoses in 822 patients. Of these patients 261 (29.4%) did not reveal coronary calcium. In younger patients (< 60 years) without stenosis exclusion of coronary calcium was a frequent finding: 31% of men and 55.8% of women were free of coronary calcium. Thus, exclusion of coronary calcium with electron beam tomography defines a substantial subgroup of patients who have an extremely low risk of significant coronary stenosis despite suspected coronary artery disease in history and non-invasive testing. Determination of coronary calcium might, therefore, be an effective filter before invasive angiography in selected groups of symptomatic patients. PMID- 11220084 TI - [Determination of right ventricular ejection fraction by thermodilution catheter technique during exercise: a comparison with radionuclide ventriculography]. AB - Since the development of a Swan-Ganz Thermodilution Ejection Fraction Catheter, several studies have been published which compare this technique for obtaining right ventricular ejection fraction (RVEFTD) with alternative methods. However, the reliability of RVEFTD measurements under exercise conditions remains undetermined. Therefore, the aim of the present study was to evaluate RVEFTD with the Gated Blood Pool method (RVEFGBP) under exercise conditions. Twenty patients with different cardiac diseases (coronary artery disease, valvular incompetence, cardiomyopathy) underwent right heart catheterization, including RVEFTD and simultaneous RVEFGBP determination at rest and during supine bicycle exercise. Cardiac index at rest-/exercise was 2.9 +/- 0.8/5.7 +/- 2.2 l/min/m2, mean pulmonary artery pressure was 15 +/- 5/25 +/- 8 mmHg, RVEFTD was 38 +/- 6/41 +/- 11% and RVEFRNV was 39 +/- 6/43 +/- 8%. Linear regression analysis showed a significant correlation between RVEFTD and RVEFGBP at rest (r = 0.72, p < or = 0.0005) and during exercise (r = 0.72, p < or = 0.0005). It is concluded that the Thermodilution Ejection Fraction Catheter is a useful device for reliable, repetitive and safe RVEF measurements, not only at rest but also under exercise conditions. This is clinically important, because RVEF, as a sensitive parameter of primary or secondary right ventricular dysfunction, can be determined in the course of standard right heart catheterization. PMID- 11220085 TI - [Is brain blood supply affected by changes in cardiac volume? Measurements of brain blood supply in healthy subjects during volume overload and in patients with artificial pacemaker by changing the pacing rate]. AB - A constant cerebral blood flow (CBF) in the presence of systemic blood pressure changes and cardiac output (CO) alterations during physiological conditions are postulated by the mechanism of cerebral autoregulation. The aim of the present study is the analysis of CBF in pacemaker (PM) patients with unspecific neurological symptoms. CBF was measured in 9 controls and 23 pacemaker patients with 133xenon, CO using Doppler echocardiography or impedance cardiography. Mean and individual CBF in controls remained unchanged when a CO increase of 28% induced by volume overload was observed. In PM patients a mean CO increase of 38% induced by an increase of basic pacing rate caused different effects of CBF. CBF increased or decreased by about 10% or remained constant. In summary, the data suggest an impairment of cerebrovascular function in those patients with concomittant CBF changes due to CO alterations (15/23 approximately equal to 65%). Thus, the analysis of brain perfusion in PM patients with unspecific neurological symptoms is possibly a new diagnostic feature in the future. It can be discussed whether or not indication and optimizing of pacemaker therapy has to be additionally analyzed by determination of endorgan perfusion. PMID- 11220086 TI - [Detection of circulating cerebral microemboli by transcranial Doppler ultrasonography]. AB - Thromboembolic events represent a major complication of cardiovascular diseases and interventions. Although general risk factors and predictors for thromboembolic events are well known from population-based studies, hardly any therapeutic consequences for the individual patient can be drawn, e.g. for a well balanced therapy with anticoagulants. A new approach towards an optimised therapy adapted to the individual risk of each patient may be based on the detection of circulating microemboli by transcranial Doppler sonography. With this technique, gaseous or solid microparticles circulating in the blood can noninvasively be detected. Due to their small size, they do not induce thromboembolic events themselves. However, several studies demonstrate that they indicate an increased thromboembolic activity and correlate directly with manifest stroke or emboli. From a transcranial Doppler probe positioned on the temporal plane at the patient's skull, the middle cerebral artery's blood flow is recorded and is analysed acoustically and optically for circulating microemboli. This technique has already been used for risk stratification of high-risk patients and therapeutic decision-making in neurologic routine, e.g. for the indication to anticoagulate the patient or for carotis surgery. Data to evaluate its value in cardiology are limited and based on few clinical studies. In this review, the basic principles and the methodological and technical background for the detection of microemboli, as well as current limitations, are discussed. Furthermore, clinical studies and their results evaluating this technique in patients with cardiological diseases and during cardiovascular interventions are reviewed. PMID- 11220087 TI - [Acute thrombosis of pelvic and leg veins in agenesis of the renal segment of the inferior vena cava]. AB - A 19-year-old, otherwise asymptomatic man presented to the hospital of orthopaedic surgery with acute severe pain like lumbago. Symptomatic treatment was performed after extensive orthopaedic diagnostic procedures. On the third day after admission he showed clinical signs of deep vein thrombosis with painful swelling and livid discoloration of both legs. Colour duplex ultrasound revealed complete thrombosis of the leg and pelvic veins bilaterally, but the cranial extent was not clear. Contrast-enhanced helical computer tomography of the abdomen and the pelvis confirmed deep pelvic vein thrombosis and showed extension into the inferior vena cava. Moreover, the study revealed the agenesis of the renal segment of the inferior vena cava with collateral flow through dilated lumbar veins to enlarged azygous and hemiazygous, through vertebral and paravertebral venous plexus. The renals were drained via dilated capsular veins. The agenesis of renal vena cava is a very rare anomaly causing acute thrombosis of the deep leg and pelvic veins. Other risk factors of thromboembolic disease were not found. The patient was treated successfully with systemic thrombolysis. Therefore we used ultra-high streptokinase infusion (9 million units over 6 hours). Colour duplex ultrasound revealed good flow into deep leg and pelvic veins after three cycle of lysis. Magnetic resonance angiography of the abdomen and pelvis was performed to evaluate the successful fibrinolysis with complete recanalisation of the pelvic veins and to demonstrate the venous anatomy. Permanent oral anticoagulation with phenprocoumon is indicated to decrease the high rate of recurrent thrombosis. Compression stockings were prescribed. To prevent thrombosis, additional risk factors like smoking, immobilization and unusual physical activity should be strictly avoided. PMID- 11220088 TI - [Cardiopathia fantastica: case report and literature review]. AB - We describe the case of a 71-year old medical technician, who was treated for instable angina pectoris in 29 different hospitals 38 times over 9 years. Dramatically presented retrosternal pain regularly started in crowded places, such as bus or railway stations or directly in front of the hospital. Ultrasound and ECG gave evidence of an old inferior myocardial infarction. Invasive diagnostic procedures were rejected by the patient because of an alleged allergy for contrast media. The single, retired patient never admitted former cardiac hospitalizations and restrained the physicians from contacting his local doctor. The patient mostly left the hospital against medical advice and achieved hospitalization in another clinic sometimes the same day. Because of his personality structure, the dramatic presentation of his complaints and the numerous hospitalizations in various hospitals with self-discharge, we made the diagnosis of a cardiac Munchausen syndrome, a so-called cardiopathia fantastica, in the presence of an accompanying coronary heart disease. In the literature we found 52 cases of cardiopathia fantastica since the first description of this phenomenon in the year 1953. Interestingly enough, mostly men were identified. Angina pectoris is by far the most frequent symptom of cardiopathia fantastica. In 8 of 53 patients (15%) an additional cardiac manifestation was present in addition to cardiopathia fantastica. Cardiopathia fantastica on the one hand is an important differential diagnosis of coronary heart disease; on the other hand it may develop in the presence of an underlying cardiac disease. PMID- 11220089 TI - [Molecular genetic diagnosis in cardiology]. AB - Within the next few years the "book of life" will be written, i.e., the sequence of the human genome will be completely assembled. This knowledge will open new avenues for the understanding and treatment of diseases. Causal relationships between mutated genes and disease states have been established for a number of single gene disorders. Although molecular genetic tests are not yet feasible for routine clinical practice in most cases, faster and, eventually, less expensive technologies for the identification of mutations are on the horizon. Clinical guidelines also apply to molecular genetics with diagnostics test being performed only in those individuals who may benefit from it. PMID- 11220091 TI - ["Trust is good, ... is control better?"]. PMID- 11220090 TI - [Endovascular stent-graft prosthesis in aortic aneurysm]. AB - Descending thoracic and abdominal aortic aneurysms represent a potential life threatening situation. Resection and graft replacement of the pathologically altered aorta used to be the preferred method of treatment. Although progress has been achieved during the past decades in the management of patients with thoracic aortic aneurysms by new surgical techniques, intraoperative monitoring of somatosensory-evoked potentials, and spinal cord fluid drainage, postoperative morbidity and mortality rates still remain high. The afflicted population is usually of older age and present at the time of operation with various comorbidities such as hypertension, obstructive pulmonary disease, coronary heart disease, all of which with significant impact on surgical outcome. Postoperative complications, such as paraplegia, renal and pulmonary disease, contribute to prolonged hospital stay and higher medical cost. In this review we report on a promising alternative approach to the surgical treatment of thoracic and abdominal aortic aneurysms, namely the currently emerging utilization of the endovascular stent-graft prosthesis in both thoracic and abdominal aneurysm. PMID- 11220092 TI - [Pathohistological findings in liver metastases]. AB - Metastatic tumors are the most common malignancies of the liver. The frequency distribution of the primary tumor location site closely resembles the frequency distribution of primary cancers in general. Yet, due to the liver's filter function of the portal blood-stream, metastatic tumors of the gastrointestinal tract are overrepresented. Most metastatic tumors show a nodular growth pattern with a demarcation of the tumor by inflammatory or fibrous reactive tissue; a diffuse metastatic tumor spread within the sinusoids is uncommon. Metastatic liver tumors may be the first clinically detectable manifestation of an unknown primary tumor. In these cases, the histological and immunohistochemical pattern of the metastatic tumor cells may give a clue of the location of the corresponding primary tumor. PMID- 11220093 TI - [Basic principles and general practice of digital photo- and video-documentation. 2]. PMID- 11220094 TI - [Improvement in diagnosis of liver metastases with the multi-detector CT]. AB - The introduction of multidetector computed tomography in clinical routine creates a new dimension of increased spatial and temporal resolution in CT scanning. On the basis of the very short acquisition time, the whole liver can now be scanned within one breathhold. Multidetector-CT allows the examination of the liver with nearly isotropic data sets. This is the prerequisite for the optimal assessment of very small liver lesions in all planes and excellent enhancement of liver lesions in defined organic perfusion phases. The speed of multidetector-CT can either be used to reduce the time to cover a given volume, or to use narrower beam collimation to increase the resolution of details along the z-axis and to reduce volume averaging. We report our clinical experiences in hepatic multidetector-CT examinations and optimized examination protocols in the assessment of hepatic metastases. Multidetector-CT and the use of interactive multiplanar reconstructions improve the detection and characterization of liver metastases. However, new problems in data management may arise from the large amount of data generated by multidetector-CT. PMID- 11220095 TI - [Contrast medium enhanced magnetic resonance tomography of liver metastases: positive versus negative contrast media]. AB - The development in oncologic liver surgery as well as modified interventional therapy strategies of the liver have resulted in improved diagnostic imaging. The evolution of contrast agents for MR imaging of the liver has proceeded along several different paths with the common goal of improving liver-lesion contrast. In MRI contrast agents act indirectly by their effects on relaxation times. Contrast agents used for hepatic MR imaging can be categorized in those that target the extracellular space, the hepatobiliary system, and the reticuloendothelial system. The first two result in a positive enhancement, the last one in a negative enhancement. Positive enhancers allow a better characterization of liver metastases using dynamic sequence protocols. Detection rate of liver metastases is increased using hepatobiliary contrast-enhanced MRI compared to unenhanced MRI. Negative enhancers, iron oxide particles, significantly increase tumor-to-liver contrast and allow detection of more lesions than other diagnostic methods. Iron-oxide enhanced MRI enables differential diagnosis of liver metastases comparing morphologic features using T2 and T1-weighted sequences. PMID- 11220096 TI - [Indications and outcome of liver metastases resection]. AB - Liver resection with curative intent for metastastic disease can be performed at low operative morbidity and mortality (< 3%). Most data relate to colorectal metastases. Five year survival following primary and repeat liver resection is consistently reported as 25-30% and has not been improved by adjuvant chemotherapy. Options for improvement of prognosis by purely technical means appear limited. Instead, future strategies should aim at increasing the number of patients amenable to potentially curative liver resection. This could be achieved by earlier diagnosis, by combination of surgical resection with neoadjuvant treatment or thermoablation, by selective portal embolisation as well as further surgical specialisation. The search for effective adjuvant therapy should continue. PMID- 11220097 TI - [Thermal ablation of liver metastases. Current status and prospects]. AB - PURPOSE: To present thermal ablation of liver metastases via laser induced thermotherapy. MATERIAL AND METHODS: Different technical procedures of thermal ablation and online monitoring are used, as there are the MR-guided laser induced thermotherapy (LITT) and the radiofrequency ablation thermotherapy (RF). RESULTS: In a prospective non randomized study 606 patients with liver metastases were treated via MR-guided laser induced thermotherapy. Inclusion criteria were the exclusion of extrahepatic tumor spread and a number of metastases lower than 5 and a size lower than 50 mm in diameter. The local tumor control rate in the 3 month and 6 month control study was 98.3%, the complication rate 3.5% (clinically relevant: 1.2%). The mean survival rate was 40.9 months for all patients with liver metastases without statistically relevant differences for various primaries, like colorectal carcinoma, breast cancer and various other tumors. Results for radiofrequency are so far limited with incidence of a higher local tumor recurrence rate versus LITT. CONCLUSION: MR-guided LITT results in a high local tumor control rate with improved survival. PMID- 11220098 TI - [MRI-assisted brachytherapy of nonresectable liver metastases. Preliminary technical and clinical experiences]. AB - PURPOSE: To evaluate the feasibility and efficacy of MR-guided interstitial brachytherapy of non-resectable liver metastasis. METHODS: Liver metastases (0.8 5.2 cm in diameter) were treated during a prospective phase I/II study using an open 0.2 Tesla MR system (Magnetom Open Viva, Siemens, Erlangen). MR-compatible brachytherapy applicators were placed percutaneously under MR-guidance in an open 0.2 Tesla MR system (Magnetom Open Viva, Siemens, Erlangen) using fast T1 weighted sequences. Pretreatment and follow-up studies were performed using a 1.5 Tesla MR system. RESULTS: Preliminary results of an unpublished prospective study are discussed exemplary on 2 selected patients. The median procedure time was 4.9 h. No major complications were observed and late effects were acceptable. In large symptomatic metastases only a temporary relief of pain was achieved. In smaller metastases (DM 3 cm) a tumor control was observed. CONCLUSION: MR-guided brachytherapy is feasible and has the potential to ablate liver metastases with diameter of less than 3 cm. Further developments are necessary. PMID- 11220099 TI - [Stereotactic irradiation of liver metastases]. AB - PURPOSE: A number of minimal-invasive methods have been developed for the treatment of non-resectable liver metastases. A focused high dose can be delivered to a liver tumor with sparing of surrounding normal liver tissue using non-invasive stereotactic techniques. METHODS: Sixty-six metastases were treated stereotactically in 43 patients during a phase 2 trial. RESULTS: There were no major side effects observed. The actuarial local control was 82% after 18 months. The median actuarial survival was 24 months. However, there was a significantly improved survival in patients without additional extrahepatic tumor manifestation at the time of treatment compared to those, who were treated in palliative intention (87% vs. 24% after 18 months, p = 0.001 (log-rank). CONCLUSION: Stereotactic single dose irradiation is a non-invasive and safe treatment option for patients with inoperable liver metastases. Phase III studies will further evaluate this new approach. PMID- 11220100 TI - [Radiofrequency ablation of liver metastases. Technique and initial results]. AB - Primary and secondary malignant hepatic tumors are the most common tumors with a much more higher incidence of hepatic metastases. Chemotherapy and radiation therapy are in general ineffective. Therefore, surgical resection is considered the method of choice in the treatment of malignant hepatic lesions. Due to systemic disease, general medical or procedure-related reasons hindering surgery, only 25 to 45% of the patients with metastatic disease of the liver are suitable for a curative surgical therapy. In resectable lesions thermoablative methods can offer an alternative to the surgical therapy. The most experience exists in radiofrequency ablation techniques. Technique, indications, contraindications, and limitations of the radiofrequency ablation will be discussed together with a presentation of own cases and a review of the literature. In 37 patients the primary technical success rate of the ablation was 97.3% (72 of 74 lesions). In 4 cases a hematoma of the liver capsule occurred. One of these had to be treated interventionally. During the limited follow-up period of 9 months no local recurrency was seen, however 4 patients developed new hepatic metastases. Beside differences in practicability it is not yet clarified if there are differences in the therapeutic efficacy of the different thermoablation methods. Nevertheless, the results of the ablation therapy may parallel the results of the surgical resection. Interstitial thermotherapy can provide a valuable contribution to local tumor control. However, the final significance of the thermoablation techniques within oncological therapy regimens has to be evaluated in further multidisciplinary studies. PMID- 11220101 TI - [MRI-controlled percutaneous cryotherapy of liver metastases]. AB - The prognosis for patients with liver metastases depends on the therapeutic options regarding the treatment of the primary tumor, co-existing extrahepatic metastases and the extent and treatment possibilities of the hepatic metastases themselves. Numerous curative or palliative oncological therapeutic concepts have been introduced in case of non-resectable liver metastases to prolong survival while maintaining a highest possible quality of life. Cryotherapy, which can be performed percutaneously and under magnetic resonance guidance, is one of these manifold therapeutic modalities, combining the inherent advantages of MRI with minimal invasiveness. Excellent visualization of the frozen liver tissue, precise tumor ablation, as well as an almost painless intervention due to the analgetic effect of the ice are implicating percutaneous cryotherapy as an attractive alternative to other ablation techniques. First clinical results are promising. However, meticulous and extensive long-term evaluation on a broad clinical scale is required. PMID- 11220102 TI - [Ultrasound diagnosis of liver metastases with liver-specific contrast media]. AB - In recent years sonographic contrast agents which can be used for liver imaging have become available. Some of these agents (e.g. Levovist, Schering AG, Berlin) display a liver-specific late phase. Visualisation of this late phase requires contrast-specific imaging techniques such as phase or pulse inversion. When scanned in phase inversion during the late phase, normal liver parenchyma shows strong enhancement. This enhancement spares metastases which stand out as echo poor or almost echo-free enhancement defects. This improves the conpicuity of metastases markedly. The technique increases the number of detectable metastases in up 45% of patients in comparison to unenhanced sonography. In a multi-centre study on 128 patients the sensitivity in the detection of individual metastases was increased from 71% to 88% and specificity improved from 59% to 88%. Contrast enhanced sonography thus represents a promising alternative to other cross sectional imaging modalities in the diagnosis of hepatic metastases. PMID- 11220103 TI - [Transarterial chemoembolization (TACE) of liver metastases. A palliative therapeutic approach]. AB - Metastatic involvement of the liver determines the treatment. Hepatic artery chemoembolization (TACE) represents a safe palliative treatment for patients with unresectable liver metastases. Technical treatment, indication and results of the TACE are reported. The results of TACE depend on primary cancer, size and vascularisation of the hepatic tumors. Our results with out patient treatment of 245 patients prove that TACE results in a extremely low rate of side effects. Combination of TACE with local ablative treatment may present potentially curative treatment option for unresectable tumors. PMID- 11220104 TI - [Radiation exposure of the patient by intraoperative imaging of intramedullary osteosyntheses]. AB - MATERIAL AND METHOD: 39 patients with pertrochanteric femur fracture (n = 32) or lower leg fracture (n = 7) were treated with closed intramedullary nailing. The related radiation exposure of the patients was calculated. RESULTS: Osteosynthesis of pertrochanteric fractures took less fluoroscopic time than osteosynthesis of lower leg fractures. The effective dose was 14 mSv for nailing osteosynthesis of proximal pertrochanteric fractures and less than 0.1 mSv for osteosynthesis of distal lower leg fractures. CONCLUSION: Radiation exposure of the patient due to intraoperative fluoroscopic imaging during osteosynthesis can be estimated based on the data given above. Intraoperative observations imply, consequent application of radiation protection by the orthopaedic surgeons may reduce intraoperative radiation exposure even more. PMID- 11220105 TI - [Puzzling liver findings. Peliosis hepatis]. PMID- 11220106 TI - Me and Max: a misalliance of goals. PMID- 11220107 TI - Thinking, talking, playing: the peculiar goals of psychoanalysis. PMID- 11220108 TI - Reflections on the goals of psychoanalysis, the psychoanalytic process, and the process of change. PMID- 11220109 TI - Life goals and psychoanalytic goals from a historical perspective. PMID- 11220110 TI - No search or getting down to business? PMID- 11220112 TI - The patient's experience of therapeutic benefit. PMID- 11220111 TI - "Butterflies caught in the network of signifiers": the goals of psychoanalysis according to Jacques Lacan. PMID- 11220114 TI - When the fruit ripens: alleviating suffering and increasing compassion as goals of clinical psychoanalysis. PMID- 11220113 TI - The treatment of affects: an interdisciplinary issue. PMID- 11220115 TI - Expanding psychological possibilities. PMID- 11220116 TI - Psychoanalysis and life. PMID- 11220117 TI - Psychoanalytic goals: new and old paradoxes. PMID- 11220118 TI - The goals of clinical psychoanalysis: notes on interpretation and psychological development. PMID- 11220119 TI - Survival analysis within one year of first acute myocardial infarction: comparison between non-Q and Q wave myocardial infarction. AB - BACKGROUND: Non-Q wave Myocardial Infarction (non-Q AMI) is related pathophysiologically to Q wave AMI, as each represents different stages of plaque rupture and thrombosis. Post-hospital re-infarction and recurrent angina are more frequent in non-Q AMI than in Q wave AMI, offsetting the higher early risk with Q wave AMI, with one-year survival rates similar in the two types of MI. OBJECTIVES: 1--Evaluation of early (< or = 28 days) and one-year total mortality from first non-Q AMI in comparison to QMI. 2--Analysis of recurrent acute ischaemic events (non-fatal reinfarction and unstable angina) in both types of MI in the same periods of time. POPULATION AND METHODS: A retrospective study of 1146 patients, mean age 65 +/- 13 years, 65% male, admitted at CCU with a first MI, from January 1988 to December 1997 (minimum follow-up period of one year, mean follow-up 42 +/- 37 months). We compared the baseline demographics and clinical characteristics (coronary risk factors, previous angina, MI evolution, recurrent cardiac events, 28 day mortality and one year mortality) of patients with non-Q AMI (NQ group = 239) and Q wave AMI (Q group = 907). RESULTS: The NQ group patients were significantly older (mean age: 67 +/- 12.6 vs 65 +/- 12.5 years; p < 0.05), included fewer smokers (29% vs 43%; p < 0.001) and were more symptomatic before the index infarction (stable angina: 40% vs 30%; p < 0.05; unstable angina: 16% vs 6%; p < 0.001), when compared to the Q group patients. There were no significant differences in MI evolution, in Killip-Kimbal class > or = 2, recurrent angina and in-hospital mortality (Q-12% vs NQ-9%; ns), although there was a higher combined risk of arrhythmias and AV conduction disturbances in patients with QMI (Q-34% vs NQ-26%; p < 0.05). The combined risk of unstable angina and reinfarction at one year was significantly higher in group NQ (NQ-13% vs Q-8.1%; p < 0.05). The NQ group showed no significant difference in 28 day total mortality (NQ-14% vs Q-17%; ns) or at one year follow-up (NQ-24% vs Q-26%; ns) when compared to the Q group. CONCLUSION: 1--Despite a lower severity of non Q AMI in the acute phase, 28 day and one year total mortality were similar in the two groups. 2--Patients with non-Q AMI showed a higher incidence of recurrent ischemic events at one year follow-up. PMID- 11220120 TI - Role of autonomic nervous system and hemodynamics in cardiovascular homeostasis after orthostatic stress. AB - Autonomic control of hemodynamics is crucial to maintaining cardiovascular homeostasis after orthostasis. Our goal was to assess the effect of passive orthostatic stress on cardiovascular hemodynamics regulation by analysis of the autonomic nervous system (ANS) and gender influence on the variables. We used a passive 70 degrees tilt test as an orthostatic maneuver. For SNA measurements we used FFT for HRV and SBPV, temporal sequences and alpha index to calculate baroreceptor gain. Hemodynamic data was calculated non-invasively by modelflow. Orthostatic stress induces a rise in heart rate (+15%), total peripheral resistance (+28%), sympathetic tonus (LF_nu: +32%; LF_pas: +64%) and a reduction in cardiac output (-28%), systolic volume (-43%), and vagal activity both tonic (HF_nu:-115%) and reflex (BRG:-103%). Females had higher vagal activity regardless of position. We concluded that the autonomic nervous system plays a crucial role in cardiovascular hemodynamics control to maintain homeostasis after orthostatic stress. PMID- 11220121 TI - [Acute effects of tobacco and vascular risk modulated by genetic factors]. AB - Most studies regarding the acute effects of cigarette smoking refer to the higher sympathetic and adrenomedullary activity as a result of sympathetic ganglia and adrenal medulla nicotinic receptor activation. Although it is reasonable to suppose that the renin-angiotensin system might be activated, this possible effect of nicotine has not been studied. We have studied the effects of cigarette smoking on blood pressure, cardiac output, pulse pressure, renin-angiotensin system, kinins-NO, oxidative stress and insulin. Also, we have investigated if the variability of the biochemical parameters was dependent on genetic polymorphisms of the angiotensin converting enzyme and the acute phase protein haptoglobin. 39 normotensive individuals, 18 males and 21 females, of mean age 35.4 +/- 8.9 years were included in this study. Oxidative stress was dependent on the ACE I/D and Hp1/2 polymorphisms, with the ACE DD genotype and the Hp2-2 phenotype not showing variation in the anti-oxidant defense systems, and the ACE II-ID genotypes and Hp1-1 + 2-2 phenotypes showing a higher anti-oxidant response, hence a lower cardiovascular risk being predictable in the latter individuals. PMID- 11220122 TI - [Effect of programming different AV intervals on mitral insufficiency in patients with DDD pacemaker]. AB - OBJECTIVE: To study the effect of programming three different atrioventricular intervals (AVI) on mitral insufficiency (MI) in patients with permanent pacemaker due to complete atrioventricular block. METHODS: We included 9 patients (mean age 62 +/- 11 years; 6 men), with permanent DDD pacemaker, isolated MI and normal ventricular function. We evaluated MI (in a quantitative way) and cardiac output (CO) through echocardiographic examination with three different AVI (100, 150 and 200 ms). RESULTS: We observed a reduction in the severity of MI with the reduction of the AVI (best results obtained with AVI of 100 ms). We also observed an increase in the CO in 4 patients (those with MI of greater degree) with AVI of 100 ms. CONCLUSIONS: We observed a correlation of longer AVI with greater degree of MI; our results point to the possibility of increasing the CO of patients with greater degrees of MI with shortening of the AVI (probably due to a partial recovery of the regurgitant volume). PMID- 11220123 TI - [Interatrial electromechanic resynchronization by dual atrial pacing in the prevention of paroxysmal atrial fibrillation --report of a case]. AB - We presented the case of a 78 year old woman who five years ago underwent myectomic surgery, and aortic valvular replacement, for obstructive cardiomyopathy and valvular aortic stenosis. After surgery, the aortic transvalvular gradient was insignificant (20 mm/Hg). In spite of this she suffers from frequent AF crises, (3 times a month), with a cardiac frequency of 140 150/min. She was in sinus bradycardia (40-45/min), which was a clear counter indication for the use of antiarrhythmic drugs. Her ECG showed sinusal bradycardia with 45/min, a two-phase P-wave (positive-negative) in DII, DIII aVF, and bimodal P-wave in DI. Furthermore, she showed a 1st degree auriculo ventricular block with complete left-branch block. In her echocardiogram there was concentric left ventricular hypertrophy, with diastolic disfunction and left atrial dilatation. In the auricular IEGM we observed a slowed-down interauricular conduction (right atrium-left atrium = 120 msecs); The A-wave was fragmented. The auriculo-ventricular Wenckbach point was at 90/min. In view of these findings we proceeded with the implantation of a DDD-pacemaker with biauricular stimulation, as follows: 1. We used two auricular electrodes, one with an active fixation to the crista terminalis of the right atrium and the other (having in mind the stimulation of the left atrium) applied to the proximal coronary sinus. These two electrodes were connected to the auricular pin of the pacemaker by means of an "Y"--type Biotronick adaptor. 2. The right ventricular stimulation was done with a normal, bipolar ventricular electrode, on the apex of the ventricle. After biauricular, simultaneous, stimulation, we proceeded with interauricular re synchronization. After this procedure, the A-wave no longer appeared fragmented, and the right auricular--left auricular waves were then simultaneous and with two phase morphology. Three months later the interauricular resynchronization procedure was induced and without any antiarrhythmic drugs, the Holter showed no cardiac arrhythmias, there is no auricular fibrillation. The morphology of the P wave has changed. The patient has an improved exercise capacity and a better quality of life. PMID- 11220124 TI - [Numbers needed for treatment and their respective confidence intervals: useful tools to assess clinical significance and uncertainty associated with medical interventions]. AB - This is a narrative review of a concept--number needed to treat (NNT). The proprieties of NNTs are described. Furthermore NNTs as important tools for medical decision are discussed. In particular, conditions that make calculus and the interpretation of NNTs somewhat more complex are commented. Namely, we consider situations where the results are not primarily binary or are expressed as "time to event" or come from a meta-analysis. The inconsistencies that might occur when NNTs are calculated from meta-analysis are discussed in some detail. Definitions for parameters derived from NNTs, as numbers needed to harm (NNH), unqualified success (NNTUS) and unmitigated failure (NNHUF) are given. Finally the usefulness of NNTs and absolute risk reductions to communicate risk to individual patients are considered. It is concluded that despite NNTs being powerful tools for medical decision, in the case of communicating risks to the individual patient absolute risks might be preferable. PMID- 11220125 TI - [Certification in interventional electrophysiology]. PMID- 11220127 TI - [Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease]. PMID- 11220126 TI - Anomalous origin of the left coronary artery from right coronary artery ostium. PMID- 11220128 TI - [State and problems of health resort construction in the Caucasian Mineral Waters Region]. AB - Although the requirement of population in recreation and rehabilitation services is increasing, the number of Russians using spa treatment at institutions of Caucasian Mineral Water Health Resort is now 3.5 times less than at the end of the eighties. The author suggests approaches to and methods for solution of problems of health resorts and their institutions, which should serve as landmarks for managing actions at regional and local levels. PMID- 11220129 TI - [Organization and evaluation of activities of a diagnostic center]. AB - Sums up the 12-year activities of Territorial Diagnostic Center in Krasnodar. Offers for discussion the key problems in improving the efficiency of such centers. PMID- 11220130 TI - [Role of various sources of financing in the activities of a consultation and diagnosis center]. PMID- 11220131 TI - [Effects of information media on population health]. AB - Analysis of sociohygienic statistical values brought the author to a conclusion that deterioration of health of the Russian population and increased mortality, particularly from causes associated with information, is directly (increased morbidity and disability caused by mental disorders) and indirectly (cardiovascular diseases) determined by unfavorable information media of Russia, and deterioration of population health in general is indicative of negative effects of information on population health in Russia. PMID- 11220133 TI - [Compensation for expenditures of municipal public health institutions in health resort regions]. AB - Analyzes and suggests a mechanism for compensation of expenditures of medical institutions of health resort regions for services rendered to visitors to these regions through insurance system. PMID- 11220132 TI - [Health care of workers of industrial enterprises in Ukraine]. AB - Presents the conceptual basis for recreating the system of primary health care of workers of industrial enterprises under modern conditions. Organization of medical care under modern economic conditions is shown as exemplified by a specially designed model of medical care of workers of atomic power station. PMID- 11220134 TI - [Methods of management of sanatoria for patients with urologic diseases]. AB - Presents experience gained in development and introduction of managing technologies in organization of spa and health resort rehabilitation of urological patients--a population relatively new for the Black Sea health resorts. PMID- 11220135 TI - [Current problems in the formation of a system of monitoring health status of children and adolescents]. AB - Discusses obviously limited potentialities of obtaining systematized analytical data by organs and institutions of social sphere. Such potentialities are particularly low in public health, specifically pediatric research and practice, where analytical materials would help improve the development of strategic programs of maternity and childhood protection and adopt adequate managing solutions at all levels. One of the constructive decisions aimed at the formation of a system of sociohygienic monitoring of children's health and ensuring integration of efforts of all responsible organs is creation of Federal Center of Social prevention for Children and Adolescents. The Center will ensure economy and rational utilization of finances and staff at the state and territorial level. Its purpose is to unite the interests of all profile organs and institutions for ensuring social well-being of children and adolescents. PMID- 11220136 TI - [Evaluation of the quality of hospital care of prisoners (results of sociological interviews)]. AB - Interregional hospital attached to administration of prisons renders specialized care to prisoners. Anonymous sociological questionnaires distributed among 815 patients treated at the hospital showed that the patients were satisfied with organization of medical care and communal provision and demonstrated serious problems in organization of hospital care rendered to prisoners. PMID- 11220137 TI - [Organizational and legal problems of medical care of traffic safety]. AB - Medical aspects of driving safety are discussed. Legal problems in first care of victims of accidents and evaluation of fitness to driving are analyzed. The paper is addressed to specialists in public health management. PMID- 11220138 TI - [Restructuring of hospital care in a large city]. PMID- 11220139 TI - [Prevention in the formation of a regional model of public health]. PMID- 11220140 TI - [Systems of payment for medical care]. PMID- 11220141 TI - [Experience in the analysis of intake and distribution of finances in sanatorium spa institutions]. PMID- 11220142 TI - [Pre-history of preparing the "Supplemental enactment concerning the Medical Department of the Imperial Moscow University". II]. PMID- 11220143 TI - [Zemstvo medicine in the Kazan province]. PMID- 11220144 TI - [Health insurance in the Far East in the twenties]. PMID- 11220145 TI - [History of public health in the railroad transport in Russia]. PMID- 11220146 TI - [Medicine of the medieval Russia. IV]. PMID- 11220147 TI - [Role of the family in the prevention of diseases of the oral cavity in children]. AB - Sociohygienic studies of hygienic knowledge with regard to prevention of dental diseases in children were carried out in 456 mothers and their 15-year-old schoolchildren in Ufa. The respondents were interviewed using specially designed questionnaires. The results allowed the authors characterize the performance of medical functions by parents from families differing by well-being and their role in hygienic upbringing of children. PMID- 11220148 TI - Mechanisms of G-protein coupled receptor regulation. AB - It has been realized recently that the enhanced or lowered activation of a certain receptor type brings about changes not only in the sensitivity (or density) of this particular receptor type in cell membranes by producing its desensitization or sensitization, down- or up-regulation (i.e. homologous regulation), but also it could change the function (or density) of other receptors (cross-regulation). This review is focused on mechanisms of the homologous regulation (changes in the pathway activated by the appropriate type of receptor) and possible mechanisms of cross-regulation (changes in pathway activated by other type of receptor). PMID- 11220149 TI - [Role of protein phosphorylation in the development of tumors]. AB - Phosphorylation is one of the most important ways of posttranslational modification of proteins that enables regulation of many cell physiological processes (transport, proliferation, differentiation). This reversible and very fast process is involved in all phases of cell division: in transition from G1 to S phase, progression of cells during S phase and entry into M phase. The physiological function of oncoproteins and tumor suppressor proteins that are involved in gene expression and replication are also regulated by phosphorylation. Many growth factors and their receptors are encoded by oncogenes which are mutated or overexpressed in a variety of human tumors. Mutation or overexpression of these oncogenes leads to uncontrollable cell division and transformation of normal cells to malignant. Cancer can be considered as a disease of the signalling pathways. PMID- 11220150 TI - Seizures in sleep apnea patients: occurrence and time distribution. AB - A retrospective survey of consecutive 480 adult patients (394 men, 96 women, mean age 50.3, SD +/- 10.4 years) with sleep apnea syndrome (SAS) was made in attempt to find out among them the patients with epilepsy. In total 19 subjects (17 men, 2 women, average age 55.8 +/- 8.7 years) representing 4.0% experienced at least two seizures in adult age. The average age at the first seizure was 48.4 +/- 16.1 years. Ten subjects suffered from primarily generalized tonic-clonic seizures, seven from secondarily generalized tonic-clonic seizures, one had complex partial seizures and one simple partial seizures. In 15 subjects (78.9%) the seizures occurred exclusively during sleep. Two patients (11.1%) had seizures exclusively during vigilance and in remaining two subjects the seizures occurred during sleep and vigilance. The findings of high proportion of subjects with epilepsy among SAS subjects, of late seizure onset and of predominantly sleep occurrence of seizures suggest that sleep apnea and hypopnea can facilitate epileptic seizures. PMID- 11220151 TI - The influence of traumatic brain lesion on sleep architecture. AB - The authors deal with sleep changes in patients after brain injury. Ten patients were examined with the use of daytime routine EEG and night polysomnography. The amount of REM sleep is most sensitive to brain damage and is reduced in all patients with nonspecific epileptiform changes in the EEG. Changes in deep synchronous sleep are less frequent and are not in correlation with the prevalence of epileptiform changes. Thus the reduction of REM sleep seems to be a sensitive marker of development of epileptiform EEG-changes and perhaps could play a predictive role of development of post-traumatic epilepsy. PMID- 11220152 TI - Influence of hemodialysis on selenium blood levels. AB - Selenium (Se) is considered an essential and very important trace element for humans. Blood Se levels in chronic hemodialysis (HD) patients are frequently reported to be lower than in controls. The aim of this study was to evaluate these lower Se blood levels with respect to the basic renal disease, duration of dialysis treatment, type of the membrane and dialysis solution used. We tried also to use the polynomial curve as a graphical method for rapid evaluation of a large number of Se blood levels. Se blood levels were measured before and after HD in 95 patients on chronic hemodialysis and in a control group of 20 healthy volunteers. Se blood levels were measured by atomic absorption spectrophotometry. Statistically significant increases of Se blood levels were found after HD (p < 0.001). During HD, the relatively high Se blood levels decreased and low levels increased but remained below the range of physiological values. These levels were lower than those of the control group (p < 0.001). Of the different dialysis membranes used, the greatest changes in Se blood levels were measured after HD with cuprophan membranes (p < 0.001). No significant difference in Se blood level in respect to the underlying kidney disease (chronic glomerulonephritis, tubulointerstitial nephritis, polycystic kidney disease, diabetic nephropathy) was revealed. No association of predialytic Se blood levels and the length of dialysis treatment was found. Concluding our results suggests low selenium content in dialysis solution and show that, in respect to the importance of Se for humans, its substitution is desirable. PMID- 11220154 TI - Obstruction of common bile duct caused by liver fluke--Fasciola hepatica. AB - Three cases of obstruction of the common bile duct by Fasciola hepatica with two of the patients presenting jaundice are reported. The authors have reviewed several publications concerning common bile duct obstruction by liver fluke, a quite rare complication of fascioliasis. Only nineteen cases of common bile duct obstruction caused by Fasciola hepatica have been reported in a review of medical publications during last ten years. Clinical presentation, diagnostic methods and considerations, types of surgery are fairly uniform in all of the reported cases. Almost all of patients reviewed, had the history, symptoms and signs characteristic for cholelithiasis including recurrent colic pain in right hypochondriac area, fever or subfebrile temperature, fluctuating or stabile jaundice, and palpable painful gallbladder. The laboratory findings in all cases reviewed had shown leucocytosis, eosinophilia, high or slight elevated serum bilirubin. Echographically commonly revealed dilated intra- and extrahepatic bile ducts containing one or more hyperechogenic elements with or without casting an acoustic shadow. All patients underwent open surgery, comprised with choledochotomy and if possible extraction of the fluke. Only two postoperative cases were of necessity followed by ERCP. In all of our cases the primary pre operative diagnosis was choledocholithiasis, with diagnose of fascioliasis established at the operation. According to the literature this uncertainty in diagnosis is common because of difficulties in differentiation of fascioliasis versus choledocholithiasis. Considerations for making the differential diagnosis- a history of origin or visiting in endemic area of infection, history of eating of aquatic vegetables, laboratory findings including eosinophilia, fasciola eggs in stool, sonography and radiological imaging results and enzyme-linked immunosorbent essay (ELISA) which has been shown to be rapid, sensitive and quantitative. In all three cases we have observed intraoperative significant signs for liver fascioliasis to include surface scarring of the left lobe on the liver--tracks caused by subcapsular migration and location of the hepatic lesions (these findings were also seen by two authors in literature) with resemblance to Japanese letters. The most effective drug for treatment of fascioliasis according to our experience and literature reviewed is bithionol. PMID- 11220153 TI - Our experiences with combination of enzyme therapy and laser therapy in enthesopathies. AB - The present communication brings a contribution to the confrontation of two treatment methods in enthesopathies (painful overload syndromes). In group A, 26 patients were treated by a combination of systemic enzyme therapy (SET) and non invasive laser therapy. In group B, 13 persons were treated only by therapeutic laser. The average age in group A and B was of 39.3 and 41.8 years, respectively. The representation of men and women in the two groups was almost identical. The intensity of the pain prior to the treatment and after the treatment, specified by each patient with the help of a ten-grade scale, was evaluated by the variance analysis. The combined treatment by the SET and therapeutic laser was statistically significantly more efficient (p = 0.02). On the other hand, there was also a significant difference between the two groups in baseline values of average pain intensities. These values were of 7.0 and 5.2 in groups A and B, respectively. The average value of the pain intensity in all the 39 patients was of 6.6 prior to the treatment and it was reduced to 3.5 after the treatment. PMID- 11220155 TI - [Comparison of the effectiveness of crystalloid and warm blood cardioplegia in patients with significant left ventricular dysfunction]. AB - In a group of 84 patients undergoing elective coronary artery bypass surgery and with the ejection fraction lower than 40% two types of myocardial protection were studied. Group I (41 cases) was given intermittent cold crystalloid cardioplegia and group II (43 patients) was given intermittent warm blood cardioplegia followed by normothermic reperfusion. Preoperative, intraoperative and postoperative data were retrospectively collected. There were no differences between the two groups except more rhythm disturbances in group I and higher incidence of neurological complications in group II. CONCLUSIONS: Warm blood cardioplegia is an effective, cheap and practical myocardial protection technique. PMID- 11220156 TI - [A nontraditional method of surgical treatment of an aortocaval fistula. Case report]. AB - Unusual method of aortocaval fistula and venous aneurysm repair is discussed and possible advantages of this type of surgery are cleared up. The aortoiliac prosthetic substitution and exclusion of the region, where aorta and inferior vena cava communicate without direct suture of the fistula makes the operation safer and lowers the risk of postoperative bleeding. In authors' opinion, this method is effective even in acutely rising aortocaval fistulas. PMID- 11220157 TI - [Aneurysm of the descending aorta causing destruction of vertebral bodies. Case report]. AB - A case report of 59-year-old woman with combined lesion of the aneurysm of the descending thoracic aorta and the destruction of vertebral bodies is presented. Considering the infectious aetiology of the whole lesion and the possibility of the future orthopaedic intervention we use the less usual operative approach and technique in this case. Only indirect method to prevent the spinal cord injury was used and the aneurysm was repaired with bypass and exclusion. The only postoperative complication requiring future surgery was the dissection and thrombosis of the right superficial femoral artery used for blood pressure monitoring. We perform, in local heparinization, the proximal femoropopliteal prosthetic bypass. The latter postoperative course was uneventful. Follow-up digital angiography of the aorta 12 month later showed good filling of the prostheses and normal anastomosis, X-ray film and CT scans one, three and five years after operation showed almost complete reconstruction of the vertebral bodies. This article also discusses the technical and tactical aspects of the thoracic aortic aneurysm repair and also analyses the diagnostic and therapeutic chance to influence the spinal cord ischaemia. PMID- 11220158 TI - Humanities having been taught on the First Medical Faculty of Charles University last 10 years. PMID- 11220159 TI - Polyclonal antibodies for immunochemical determination of human pepsinogens. AB - The human gastric mucosa contains two main groups of aspartic proteinases, pepsin (EC 3.4.23.1) and gastricsin (EC 3.4.23.3), which differ by their structural, kinetic and immunological characteristics. The ratios between human aspartic proteases are important from the diagnostic point of view. Rabbit polyclonal antisera against human pepsinogen A and pepsinogen C (progastricsin) were obtained and tested for clinical purposes. Immunoblotting procedure seems to be a simple and sufficiently sensitive method for qualitative determination of pepsinogens in human gastric mucosa. PMID- 11220160 TI - [Effect of growth hormone on the structure of bone spongiosa in rats]. AB - Changes in bone spongiosa, which follow after administration of growth hormone (GH) are described differently. Histomorphometrically processed value of bone trabecular volume is found higher or lower than normal. In this study, changes of rat bone spongiosa after administration of GH or bisphosphonate pamidronate were followed. The authors found statistically significant widening of histomorphometric parameter of trabecular thickness, but histomorphometrically assessed values of trabecular bone volume were not statistically different from normal rat bones. The structure of spongiosa is changed, the density of trabecular bone is diminished. The hypothesis of trabecular bone increase after GH administration together with resorption blocking agent (pamidronate) was not confirmed. GH causes widening of bone trabeculae. Pamidronate has no influence on bone histomorphometry in this case. PMID- 11220161 TI - [Personality changes in patients after voluntary alcoholism therapy from the aspect of the Rogers method]. AB - The research deals with patients dependent on alcohol (F 10.2) who were treated on a voluntary basis by psychotherapeutic and sociotherapeutic methods in seven hospitals. For ethical, legal as well as professional reasons it was impossible to form a control group. Sixty six patients (28 women, 38 men) were put to the Regensburg inventory analysis of incongruities, its statistical evaluation was done by SPSS. The aim of the research was to detect personally changes in patients induced most probably by their hospital stay. As statistically significant (t-test, u-test, alpha adjustment, effect size), we detected positive changes in the following personality variables: the patient's self-confidence (p < 0.001, ES = 1.11), favourable self concept including the ability to tolerate and manage their inner incongruities (p < 0.001, ES = 0.48), an increase of self congruent experiences (p < 0.001, ES = 0.45) and a decrease of insufficiency feelings (p < 0.001, ES = 0.40). We consider our findings as preliminary and it is necessary to prove them by further research. PMID- 11220163 TI - [50 years' of the Institute of Sports Medicine at the Charles University Medical School on the 650th anniversary of its founding]. AB - In an agreeable shadow of the great 650th anniversary of Charles University foundation (1348-1998), arising of the first Institute of Sports Medicine round the world on Medical Faculty in Prague (1948-1998) was commemorated by scientific session. Since J. E. Purkyne (1850) have gone idea of favourable effect of body training for human health by representatives of Prague Medical Faculty, till Doctor J. Kral, who started lectures for medical students in this discipline in 1933. Rise of Institute of Sports Medicine was approved in 1934, but its realization thanks to Professor Kral, was performed after 2nd World War in 1948. From the beginning, students have lectures within the framework of daily study of whole wide of the branche, including practical exercises and closing examine. First text book of sports medicine and first book about clinic in sports medicine was written (J. Kral). Members of Institute lectured on many foreign universities and scientific congresses and published more than 2,500 scientific works, some of them have world priority. For example first wireless transmission of heart frequency (V. Seliger, V. Kruta), cardiologic observations during big sports load (J. Kral, Z. Hornof), discoveries at biochemical laboratory (J. Kral, A. Zenisek), at medical functional anthropologic laboratory (V. Novotny), introducing of remedial exercises in clinical practice (L. Schmid, M. Zintlova, J. Chrastek) etc. In the set out choice of literary citation it is put on only fragment of publications which document scientific activity of jubileeing Institute. For period of duration of Institute more than hundred thousand patients were examined--both sportives and non-sportives, young and old. Contemporary trend goes from classic care about sportsmen towards preventive medicine. Attention is focused first of all to testing of middle aged and older patients in sense of prevention of cardiovascular and metabolic diseases and indication for specific movement load. In 650 years history of pedagogic and scientific success of Charles University, 50-year activity of Institute of Sports Medicine means only tiny part. In view of healthy risks, which brings modern life style and in view of worsening of environment, an important task stand before the discipline with new prevention conception. PMID- 11220162 TI - [Aenigma sensorii or the mystery of human consciousness]. PMID- 11220164 TI - [Thoughts on the infrastructure of modern pathologic physiology]. AB - Contemporary pathophysiology is essentially based upon three principal pillars of support: First the experimental method (formulated by Cl. Bernard); second experimental design (proposed by R. A. Fisher); and finally, present-day information resources, which are easily accessible in sophisticated databases, following the so-called information explosion. These three underlying principles, sensitively interrelated, should be employed appropriately when engaging in pathophysiological research or education. Three points of support invariably offer stable equilibrium, as does a tripod, and it would be an error a priori to attempt to support research work exclusively on high-tech methodology, or overreliance on statistical software, or pseudo-abundance of citations from journals enjoying a high impact factor, whilst lacking significant balancing support from either of the other two legs of the tripod--or indeed other sources altogether. If pathophysiology in Czechoslovakia is to achieve international esteem and acknowledgement, then our undergraduate and postgraduate biomedical courses must be soundly based on this tripartite infrastructure, as a starting point for our intellectual methodology in pathophysiology. (This speech was presented at June 20th, 1989 at the opening session of the Tenth Czechoslovak Congress of Pathophysiology held in Prague June 20th-23rd 1989. The text still valid, ten years after its oral presentation, is now published in this form at the occasion of the tenth anniversary of the Congress. PMID- 11220165 TI - Studies on agenesis of third molars amongst populations of different origin. AB - This study contains information on the occurrence of agenesis of one to four third molars among the population and ethnic groups of Europe, North America, Africa and Asia (Japan), based on the results of investigations carried out by dozens of authors. Recent discoveries have been supplemented with corresponding data concerning the skeletal remains of the jaws of individuals living from the ice age to the middle ages. The results show unbelievably large diversities as regards the frequency of agenesis of third molars in different populations from practically zero (Tasmania) to nearly 100% (Mexican Indians). This remarkable fact is not, however, the only reason why the problem of third molars remains a major concern for anthropologists, anatomists and stomatologists. Indeed, agenesis of third molars present only one of the most important anomalies which characterizes this tooth. It is necessary to look for the roots of the said variability in the remarkably complicated phylogenetic development undergone by the third molar from the time of our predecessors to the present day. Most of today's authors are of the opinion that although significant involution changes have occurred in third molars, that with the advent of hominization the number of teeth in individuals has stabilized at eight for every quadrant of dentition. For this reason it is not possible to regard agenesis of third molars as the manifestation of the phylogenetic reduction in the number of teeth, but as the developmental anomaly which is the result of a mutation and selection process based on heredity. The results are completed with an analysis of the value of agenesis of one to four third molars according to the individual quadrants and gender. A knowledge of these indicators is necessary in order to study the relationship between agenesis of third molars and hypodontia of the other teeth. PMID- 11220167 TI - Drugs in sport: a new approach. PMID- 11220166 TI - The effects of apomorphine on attentional processing in Parkinson's disease. AB - To ascertain whether variations in central dopaminergic transmission can differentially affect motor and cognitive processing, we studied the effects of apomorphine (APO) in 9 patients with Parkinson's disease (PD). The UPDRS motor scores and auditory event-related potentials (ERPs) obtained in the 'odd-ball' (OB) and in the 'covert orientation of attention' (COA) tasks were studied in the 'off' and in the 'on' state after an injection of APO. Although APO injection improved patients' motor status, it induced a significant increase in the latencies of the P2 and P3 ERP components in the OB. In the COA task, right-hand reaction times (RTs) were markedly shortened in the 'on' state while left hand RTs remained unchanged. The contrasting effects of dopaminergic stimulation on the motor performance and on some aspects of cognitive processing suggest the existence of complex interactions within pre- and postsynaptic brain dopamine receptors, and an intervention of segregated basal ganglia-prefrontal cortex loops in motor and cognitive behaviour. PMID- 11220168 TI - A Muslim woman with infertility. PMID- 11220169 TI - A rational approach to managing back pain. PMID- 11220170 TI - Key developments in rheumatology. PMID- 11220171 TI - The patient with cervical disc prolapse. PMID- 11220172 TI - Casebook: acute knee injuries. PMID- 11220173 TI - Mouth conditions in the elderly: Part 2. PMID- 11220174 TI - Passing the MRCGP: a practical approach to the MCQ. PMID- 11220175 TI - Trust me--I'm a patient. PMID- 11220176 TI - Consecutive geoelectric measurements reveal the downward movement of an oxidation zone. AB - An investigation program for monitoring pyrite oxidation on a conveyer bridge dump used geoelectric measurement for monitoring the progress of pyrite oxidation within the dump. The results of the geoelectric measurement show that low soil-pH and high pore water conductivity correlate with low soil resistivity values. The soil resistivity values are dominated by high pore water conductivity. The influence of changes in water saturation on resistivity was comparably low. An increase in pyrite oxidation was observed in areas with high porosity due to low dump density. Consecutive geoelectric measurements revealed locally differentiated downward movement of an oxidation zone caused by dump heterogeneity. PMID- 11220177 TI - Chemical investigations of aquifers affected by pyrite oxidation in the Bitterfeld lignite district. AB - In a large area around the former open-pit lignite mines near Bitterfeld, Germany, groundwater taken from wells was analyzed for the major cations, anions, and trace elements. Quaternary and Tertiary sediments were collected from aquifers exposed on the sides of the pits and from boreholes outside the mines and analyzed for major and trace elements, as well as for carbonate, pyritic sulfur and total organic carbon. The pH and electrical conductivity of the sediments in suspension were measured. Significant differences were determined between the Tertiary sediments of the aquifers that were exposed to atmospheric oxygen during the lowering of the groundwater table and those outside the cone of depression. The greatest differences were found in the pyrite content, the pH values, and the electrical conductivity. In order to map the degree to which the mining of the lignite has affected the quality of the groundwater in the study area, the water samples were divided into six classes on the basis of their sulfate content. The neutralization potential was calculated to estimate the potential for acidification. Prediction of future groundwater quality is based on both (i) the present composition of the groundwater, surface water, and Quaternary and Tertiary aquifer sediments and (ii) the present and future groundwater flow directions. These studies have shown which parameters are important for future groundwater monitoring. PMID- 11220178 TI - Large-scale experiments for microbiological evaluation of measures for safeguarding sulfidic mine waste. AB - In the framework of a German-Romanian scientific cooperation, experiments were performed to evaluate feasible and cheap techniques for the safe storage of mine waste to prevent acid rock drainage (ARD). A large four-chamber percolator (4CP) was installed in a waste heap at Ilba Mine, Romania, to test the effect of biocides and alkaline layers on the bacteria causing acid rock drainage (ARD). The 4CP consisted of four chambers each containing 65 m3 of sulfidic waste material. The 4CP enabled the transfer of laboratory results to a technical scale. The detergent sodiumdodecylsulfate (SDS) was proved to be active against the leaching bacteria. Organotrophic micro-organisms were not effected by the SDS application. The alkaline layers caused an increase of pH, however, a decrease of cell numbers was measured only in adjacent ore layers, but not in the whole ore body. A rapid evaluation of the effects of these countermeasures on ARD formation became possible by microcalorimetric activity measurements for bioleaching. PMID- 11220179 TI - Soil properties and water regime of reclaimed surface dumps in the North Bohemian brown-coal region--a field study. AB - This paper attempts to characterise the water regime of reclaimed surface dumps in connection with their soil physical properties. The results of a research project based on field measurements of moisture content and hydraulic conductivity, supported by analyses of undisturbed soil samples, led to recommendations regarding technological procedures for such dumps. A dielectric soil moisture meter, in an improved version, was successfully used for field monitoring and further evaluation of moisture content. Hydraulic conductivity was also measured in the field (by repeated borehole infiltration) using the Guelph permeameter method. Laplace-Gardner analysis was used for evaluating the field saturated hydraulic conductivity results. PMID- 11220180 TI - Stabilisation of bank slopes that are prone to liquefaction in ecologically sensitive areas. AB - A consequence of lignite stripping in the Lusatia mining district (East Germany) is the backfilling of dumps that mainly consist of low-compacted fine and medium grained sands. When the ground-water table, which had been lowered while stripping the coal, is rising again, these dumps might be affected by a settlement flow due to the liquefaction of soils. Common methods for stabilisation as, for instance, blasting or vibrator-jetting deep compaction, are not very useful in ecologically sensitive areas, where dumps have been afforested and embankment areas of residual lakes have developed into highly valuable biotopes. A new so-called air-impulse method in combination with directional horizontal drilling has been developed, which does not have a considerably negative impact on the vegetation during compaction. The experience gained during the first employment of this method at the lake "Katja", a residual lake of lignite stripping, is presented in this paper. PMID- 11220181 TI - Deep soil compaction as a method of ground improvement and to stabilization of wastes and slopes with danger of liquefaction, determining the modulus of deformation and shear strength parameters of loose rock. AB - For the stabilization of dumps with the construction of hidden dams and for building ground improvement, for instance for traffic lines over dumps, nearly all applied compaction methods have the aim to reduce the pore volume in the loose rock. With these methods, a homogenization of the compacted loose rock will be obtained too. The compaction methods of weight compaction by falling weight, compaction by vibration and compaction by blasting have been introduced, and their applications and efficiencies have been shown. For the estimation of the effective depth of the compaction and for a safe planning of the bearing layer, respectively, the necessary material parameters have to be determined for each deep compaction method. Proposals for the determination of these parameters have been made within this paper. In connection with the stabilization of flow-slide prone dump slopes, as well as for the improvement of dump areas for the use as building ground, it is necessary to assess the deformation behavior and the bearing capacity. To assess the resulting building ground improvement, deformation indexes (assessment of the flow-prone layer) and strength indexes (assessment of the bearing capacity) have to be determined with soil mechanical tests. Forster and Lersow, [Patentschrift DE 197 17 988. Verfahren, auf der Grundlage last- und/oder weggesteuerter Plattendruckversuche auf der Bohrlochsohle, zur Ermittlung des Spannungs-Verformungs-Verhaltens und/oder von Deformationsmoduln und/oder von Festigkeitseigenschaften in verschiedenen Tiefen insbesondere von Lockergesteinen und von Deponiekorpern in situ; Forster W, Lersow M. Plattendruckversuch auf der Bohrlochsohle, Ermittlung des Spannungs Verformungs-Verhaltens von Lockergestein und Deponiematerial Braunkohle--Surface Mining, 1998;50(4): 369-77; Lersow M. Verfahren zur Ermittlung von Scherfestigkeitsparametern von Lockergestein und Deponiematerial aus Plattendruckversuchen auf der Bohrlochsohle. Braunkohle--Surface Mining, 1995;51(1):39-47] improved a direct procedure, the so-called plate-loading test. With this improved procedure, it is possible to produce profiles of deformation parameters and shear-strength parameters of the loose rock. On this basis the settlement behavior and the bearing behavior of the ground can be described. The PDV-BS cone-penetration test and the pressiometer test are compared and the reliability of the soil mechanical indexes are assessed critically. The PDV-BS can be used as a calibration test for cone penetration tests as well as for the calibration of pressiometer tests. With the application of a PDV-BS and a pressiometer test in combination in a testing field, the anisotropy properties of the loose rock can be proved. PMID- 11220182 TI - Cover design for radioactive and AMD-producing mine waste in the Ronneburg area, eastern Thuringia. AB - At the former uranium mining site of Ronneburg, large scale underground and open pit mining for nearly 40 years resulted in a production of about 113,000 tonnes of uranium and about 200 million cubic metres of mine waste. In their present state, these materials cause risks to human health and strong environmental impacts and therefore demand remedial action. The remediation options available are relocation of mine spoil into the open pit and on site remediation by landscaping/contouring, placement of a cover and revegetation. A suitable vegetated cover system combined with a surface water drainage system provides long-term stability against erosion and reduces acid generation thereby meeting the main remediation objectives which are long-term reduction of radiological exposure and contaminant emissions and recultivation. The design of the cover system includes the evaluation of geotechnical, radiological, hydrological, geochemical and ecological criteria and models. The optimized overall model for the cover system has to comply with general conditions as, e.g. economic efficiency, public acceptance and sustainability. Most critical elements for the long-term performance of the cover system designed for the Beerwalde dump are the barrier system and its long-term integrity and a largely self-sustainable vegetation. PMID- 11220184 TI - Biogeochemical and ecological considerations in designing wetland treatment systems in post-mining landscapes. AB - Although wetlands have gained acceptance as important components of ecosystems in post-mining landscapes in the past decade, their roles in contaminant retention/removal have not been well integrated into the designing of restoration programs. This paper describes the integration of sediment microbial activities and natural precipitation processes, along with approaches to defining the contaminant load from the mine wastes. The contaminant removal rates, which can be expected by a wetland sediment, are summarized and how they need to be reflected in the wetland size required, and the carbon supply which is needed. Contaminant loading from mining wastes can be balanced by wetland ecological processes, including wetland primary production and microbial mineralization in the sediment. This ecological engineering approach is demonstrated using case studies on hard-rock mining waste in Canada. PMID- 11220183 TI - Relocation of net-acid-generating waste to improve post-mining water chemistry. AB - Acidic drainage and metal leaching are long-term environmental liabilities that can persist for many decades to millennia. One technique to improve the water chemistry and ecology of post-mining landscapes is to relocate and submerge net acid-generating mine materials in a lake or water-retaining impoundment. One example of a carefully executed relocation of waste rock took place at the Eskay Creek Mine in Canada. Pre-relocation studies included an empirical relationship that related (1) the amount of acidity retained by the waste rock during past oxidation to (2) the amount of lime needed in each truckload for neutralization of the acidity and for suppression of metal release. During relocation, thousands of rinse pH measurements indicated net acidity varied significantly over short distances within the waste rock and that acidic rock could not be reliably segregated from near-netural rock. After relocation, water from the watershed continued to be acidic for a few years, then returned to near-neutral pH and near background concentrations of metals. The chemistry of the lake where the waste rock was submerged remains near background conditions. Therefore, with careful planning and implementation, the relocation and submergence of net-acid generating materials can greatly improve post-mining water chemistry. PMID- 11220186 TI - Injury prevention rounds out public health review. PMID- 11220185 TI - Treatment of acid lignite mine flooding water by means of microbial sulfate reduction. AB - During and after mining activities acidic waters containing high amounts of heavy metals and sulfate often occur. In addition to precipitation processes, water purification is also possible with the help of sulfate-reducing bacteria (SRB). A mixed culture of SRB was adapted to methanol as a cheap carbon source. In order to receive high sulfate-reduction rates immobilization on porous materials proved to be advantageous. Continuous laboratory experiments based on immobilized SRB were carried out with original water from a lignite mining site reaching sulfate reducing rates up to 132 mg SO4(2-)/(1 h). Based on these results a process for the treatment of such waters was designed. Heavy metals are removed by recycling sulfide containing effluent, excess sulfide can be oxidized to elemental sulfur by addition of hydrogen peroxide. The plant with a 3.9 m3 bioreactor with immobilized SRB was constructed at the mine site. This pilot plant was operated successfully for some months. The removal of heavy metals was close to 100%, the pH of the acidic water increased from 3.0 to 6.9. The sulfate-reducing rate again reached 134 mg SO4(2-)/(1 h). The production of sulfur from the excess sulfide is possible. PMID- 11220188 TI - The injury epidemic: where do we stand? PMID- 11220187 TI - A current evaluation of injury programs in Wisconsin. PMID- 11220189 TI - Community-based injury prevention programs: toward a safer Wisconsin. AB - Community-based injury prevention programs are an important approach to the reduction of the burden of injury in all age groups. These programs may focus on education and behavioral change, increasing access to safer products, creating a safer environment, and passing and enforcing legislation. This article reviews some of the community-based injury prevention programs in Wisconsin that focus on the prevention of home- and transportation-related injuries. Community participation in the design and implementation of these programs will increase the likelihood of adopting safer behaviors on a community level. We are hopeful that physicians and other health care providers will be actively involved in community-based injury prevention activities in their locale. PMID- 11220190 TI - Trends in motor vehicle deaths in Wisconsin, 1986-1996: a decade of progress? AB - Motor vehicle-related injuries are a major cause of death and economic burden in Wisconsin. We examined motor vehicle-related mortality trends in Wisconsin from 1986 to 1996. During this time, overall mortality decreased by 12% and Wisconsin has met its year 2000 goal. However, mortality rates did not improve for women and non-whites. In addition, mortality rates increased in persons over 75 years. There are several explanations that may account for the overall mortality rate decline, but the reasons for the differences between age, racial, and gender groups are unclear. PMID- 11220191 TI - Graduated driver licensing in Wisconsin: a new law for teens and parents. AB - The final components of Wisconsin's graduated driver licensing (GDL) statute [Biennial state budget act 1999 Wisconsin Act 9] went into effect on September 1, 2000. The GDL system seeks to reduce the number of teen motor vehicle collisions and fatalities by gradually introducing young drivers to all driving situations, beginning with the easiest and progressing to the more difficult. The stages of licensing are defined by the degree of risk involved. When teen drivers demonstrate the ability to drive safely in a restricted setting with high levels of supervision, they "graduate" to the next licensing level with fewer restrictions. Numerous factors are associated with the high rate of teen motor vehicle crashes and fatalities. Such factors include driver inexperience and easy distractibility, alcohol use and lack of seat belt use. The GDL addresses all of these risk factors. This article reviews the injury prevention strategies incorporated in the GDL and outlines the basic components of Wisconsin's law. PMID- 11220192 TI - Fatal injuries in adolescents. AB - Injuries are a major cause of morbidity and mortality among adolescents. Adolescents routinely experiment with high-risk behaviors, increasing their risk of injury. Major modes of injury in adolescents include motor vehicle collisions, drowning, suicide and homicide. This article reviews the risk factors for fatal injuries in adolescents and discusses current prevention strategies. Previous research identifies many risk factors associated with adolescent injuries. Practitioners can help prevent teen injuries by screening all adolescent patients and identifying those at high risk of injury. Patients at high risk need preventive counseling and evaluation for possible referral to other services. Current strategies are useful in preventing many injuries; however, further research is needed to evaluate these strategies and to design new prevention programs. PMID- 11220193 TI - Preventing animal bites in children. AB - Domesticated animals have become an increasingly important part of our human experience. Children today are likely to experience daily interactions with animals within their neighborhoods and homes. These animals can provide children with companionship, the opportunity to learn responsibility and respect for life. Yet they can also present children with the potential for injury under certain conditions. Almost half of all children will suffer an animal bite at some time during their childhood, and over 15% of these bites will require medical care. This article will discuss the circumstances leading to most domesticated animal bites, provide advice to the practitioner in helping families choose kid-friendly pets and provide guidance in promoting safe interactions with animals. A future article will review the management of animal bites, including wound care, antimicrobial prophylaxis and the treatment of infected bite wounds. Doctor Corden's article in this issue (p. 43) addresses the role for rabies prevention in animal bites. PMID- 11220194 TI - Too many treatments for Parkinson's disease: yet another look. PMID- 11220195 TI - Prevention of choking, strangulation, and suffocation in childhood. AB - Choking, suffocation and strangulation are important causes of unintentional injury and death in young children. Choking on food and toys, suffocation from plastic bags and strangulation from strings on children's items are common causes of mechanical airway obstruction. An effective prevention plan must include education, product labeling, and product and container modification. Health care providers can play an important role in the dissemination of prevention information to caregivers and manufacturers in order to reduce the incidence of these injuries in young children. In the United States, mechanical airway obstruction from choking, suffocation and strangulation is the leading cause of unintentional injury that results in death of children less than 1 year. It ranks fourth as a cause of death in children 1 to 9 years, surpassed only by motor vehicle injuries, drowning/submersion, and fire/burns. Many of these deaths are preventable. Prevention of death from mechanical airway obstruction has long been a concern of health care providers, whose role may involve education of parents, other caregivers and manufacturers about the risks and the prevention of choking, suffocation and strangulation in children. Choking is the interruption of respiration by internal obstruction of the airway, usually by food or small toys in young children. Suffocation is obstruction of the airway from an external object that blocks the nose and mouth, such as a plastic bag. Strangulation also results from external compression of the airway from an object, such as a string that becomes caught around the neck. PMID- 11220196 TI - Rabies prevention. AB - Rabies is an almost uniformly fatal encephalomyelitis with no treatment option other than supportive care for those who contract the illness. Mortality worldwide is estimated to be 40,000-70,000 people annually. Fortunately, public health measures begun in the 1940s and 1950s regarding vaccination and control of domestic animals in this country and the availability of safe and effective rabies postexposure prophylaxis treatment (RPEP) for humans has made rabies a rare disease in the United States. Community healthcare providers continue to play a pivotal role in the prevention of this devastating disease. This article emphasizes the challenges that the evolving epidemiology of rabies presents to our healthcare system, especially regarding international travel, the importance of domestic animal vaccination against rabies, the use and cost of RPEP, recent rabies epizootics in wildlife populations and the role of bats in disease transmission. PMID- 11220197 TI - Farm injuries in children: a review. AB - Farming is one of the most dangerous occupations in the United States. Unfortunately, risk of injury and death extends not only to adults, but to children that live, play, and work on the farm. This article reviews the epidemiology, pathogenesis and prevention of farm injury in children and adolescents. In Wisconsin 39 children were killed in the agricultural setting between 1995 and 1999. Nationwide, over 100 children per year are killed and 27,000 injured on farms. The age distribution of injury in children is bimodal, with one peak at 3-4 years of age and a second peak at 13-16 years. Boys are much more likely to be injured on the farm than girls. Of the agents associated with the injury of children, tractors are most commonly implicated and are the most deadly. Drownings, injury by cows and horses, and other farm implements and machinery make up the remainder of most farm accidents. The head and face are the sites involved in preschoolers whereas the limbs are more likely to be injured in older children. Poor supervision, unreasonable expectations, financial difficulties and lack of safety devices are associated with risk of injury. Prevention or injury involves patient and family education, regulation and safety devices. Important resources are available for farm families and health care providers to prevent farm accidents in children. PMID- 11220198 TI - Injury data changes the debate over firearms. PMID- 11220199 TI - New guidelines published for managing community-acquired pneumonia. PMID- 11220200 TI - Strong SMS/DPH partnership needed. PMID- 11220201 TI - I was saved by a seat belt... would my 5 year old have been so lucky? PMID- 11220202 TI - [Relationship among VIP plasma levels, esophageal dysfunction, and microcirculation in systemic sclerosis]. AB - BACKGROUND: Recent studies suggest that esophageal dysmotility occurring in systemic sclerosis might be caused by neurotransmitter levels decrease. The aim of the present study is to value VIP plasma levels, and to relate them with the pressure of the inferior esophageal sphincter (IES) and the capillaroscopy score in a group of patients affected by Systemic Sclerosis (SSc). METHODS: Eleven subjects affected by SSc (eight male and three female, age from 30 to 72 years old) have been studied through esophageal manometry, capillaroscopy and VIP plasma levels evaluation. Fifteen healthy volunteers, as control group, have been enlisted. RESULTS: Our results show a decrease of VIP plasma levels in patients with SSc compared with control group. The difference between two groups has statistical significance (p < 0.01). Capillaroscopy has shown remarkable microcirculatory impairment and the esophageal manometry proved a decreased IES pressure. The scores of capillaroscopy, VIP plasma levels and pressures of IES have been compared and it has been observed that there is a relationship between VIP plasma level and pressure of IES. CONCLUSIONS: VIP plasma levels decrease enhances the role of the autonomic disorder in SSc and may contribute to produce the alteration of vascular tone as well as the gastroenteric musculature dysfunction. PMID- 11220203 TI - [Psoriasis complicated with severe mutilating psoriatic osteoarthropathy. Clinical case and review of the literature]. AB - Aim of this paper is to discuss, on the basis of an extensive critical review of the recent literature, the case of a 56-yr-old male patient who suffered from cutaneous psoriasis and psoriatic arthritis mutilans (PA) (polyarticular, symmetric, destruent and erosive) with involvement of the hands, feet and spine, associated with android obesity and mild type 2 diabetes mellitus. HLA typing of the patient showed the HLA-A3-Ax, B14-B63 and Cw4-Cw6 haplotypes, some of which are associated or correlated with susceptibility to PA. Cutaneous psoriasis is a chronic inflammatory dermatitis, with onset at any age and affecting approximately 2% of the western populations. In 5-7% of patients, it is associated with articular manifestations or true arthritis. PA is a chronic, inflammatory, seronegative arthropathy which may develop in some psoriasis patients, may involve peripheral and axial (spondarthritis) joints and may lead to severe joint destruction. Genetic, immunologic and environmental (i.e., infectious agents or trauma) factors seem to play an important role in the onset and clinical appearance of PA. Although PA is a clinically monomorphic disease, it may show different heterogenous subgroups with differences in their etiopathogenesis. When PA is suspected, it is mandatory to analyze carefully the patient's familiar history, search attentively for the specific skin features, exclude a septic arthritis (especially if the involvement is monoarticular) and, in the cases of fulminant disease, consider always the possible coexistence of an acquired immunodeficiency syndrome. PA can occasionally be an aggressive, disfigurating and disabling disease and the treatment (incisive and precocious) should be similar to that for rheumatoid arthritis. At present, a definitive therapy does not yet exist, but the majority of PA patients can lead a fairly normal life and they do not show increased mortality rates (excluding the severe cases of erythrodermic or pustulosis psoriasis). However, as a result of the various problems of occupation and morbidity it causes, PA is a disease with great social involvement. PMID- 11220204 TI - Abnormal vaginal flora, cervical length and preterm birth. PMID- 11220205 TI - High immunocontent of S100 beta protein in amniotic fluid of pregnancies with Down syndrome. PMID- 11220206 TI - Ambiguity of 'ambiguity'. PMID- 11220207 TI - Change blindness in the absence of a visual disruption. AB - Findings from studies of visual memory and change detection have revealed a surprising inability to detect large changes to scenes from one view to the next ('change blindness'). When some form of disruption is introduced between an original and modified display, observers often fail to notice the change. This disruption can take many forms (e.g. an eye movement, a flashed blank screen, a blink, a cut in a motion picture, etc) with similar results. In all cases, the changes are sufficiently large that, were they to occur instantaneously, they would consistently be detected. Prior research on change blindness was predicated on the assumption that, in the absence of a visual disruption, the signal caused by the change would draw attention, leading to detection. In two experiments, we demonstrate that change blindness can occur even in the absence of a visual disruption. In one experiment, subjects actually detected more changes with a disruption than without one. When changes are sufficiently gradual, the visible change signal does not seem to draw attention, and large changes can go undetected. The findings are discussed in the context of metacognitive beliefs about change detection and the strategic decisions those beliefs entail. PMID- 11220208 TI - Hearing by eye: how much spatial degradation can be tolerated? AB - In the McGurk effect (McGurk and MacDonald, 1976 Nature 264 746-748), illusory auditory perception is produced if the visual information from lip movements is discrepant from the auditory information from the voice. A study is reported of the tolerance of the effect to varying levels of spatial degradation (videotaped images of a speaker's face were quantised by a mosaic transform). The illusory effect systematically decreased with an increase in the coarseness of the spatial quantisation. However, even with the coarsest level (11.2 pixels/face) the illusion did not completely disappear. In addition, those participants who did not experience the illusion nevertheless showed the effects of auditory-visual interaction in their clarity ratings of the auditory stimulus. It is concluded that auditory-visual interaction in visible speech perception is based on relatively coarse-spatial-scale information. PMID- 11220209 TI - Color appearance of surfaces viewed through fog. AB - How do the colors of surfaces seen through fog depend on the chromatic properties of the fog? Prior work (e.g. Chen and D'Zmura, 1998 Perception 27 595-608) shows that the colors of surfaces seen through a transparent filter can be described by a convergence model. The convergence model takes into account color shift and change in contrast. Whether the convergence model can also be applied to fog was tested experimentally with an asymmetric matching task. In computer graphic simulation, observers adjusted the color of a surface seen through fog in order to match the color of a surface seen in the absence of fog. The convergence model fits the data well. The results suggest that the color constancy revealed in this task with fog is described best by a model that takes into account both shift in color and change in contrast. PMID- 11220210 TI - The spatial spread of attentional modulation of the motion aftereffect. AB - The spatial spread of attentional modulation of selective adaptation was investigated in four experiments in which the duration of the movement aftereffect (MAE) was measured with and without processing of intermittently changing digits at the fixation point. In the first experiment, the effects of diverting attention on MAE duration were found to reduce as the distance between the fixation digits and the inner edge of the surrounding adapt/test grating was increased. A second experiment suggested that eye movements were unlikely to underlie the attentional effects. In experiment 3, the attentional effect stayed constant as the outer diameter of the adapt/test gratings was increased. In experiment 4 (as in experiment 1) the modulatory effects of attention were larger the closer the adapt/test gratings were to the locus of attention, when the area of the grating was held constant but its eccentricity varied. In experiments 1 and 4, an intermittently changing fixation digit was found to reduce MAE durations more than an unchanging digit, even when subjects were not required to process it, suggesting that exogenous as well as endogenous attentional processes modulate early motion processing. PMID- 11220211 TI - Speed perception is affected by the Ebbinghaus-Titchener illusion. AB - We examined whether the apparent extent of motion affects speed perception. On the first presentation of each trial, a light dot travelled horizontally across a central circle of one of the Ebbinghaus configurations (with either small or large inducing elements). On the second presentation, observers adjusted the speed of a dot moving within the central circle alone so as to match the speed perceived in the first presentation. For all stimulus speeds (1.3, 2.1, and 5.5 deg s-1), the matched speed with small inducing circles was systematically less than that with large inducing circles. The findings indicate that the perceived speed depends on the apparent extent of motion: the larger the apparent size of a frame, the slower the apparent speed. These results are consistent with the predictions of transposition effects in visual motion. PMID- 11220212 TI - Variations on the Hermann grid: an extinction illusion. AB - When the white disks in a scintillating grid are reduced in size, and outlined in black, they tend to disappear. One sees only a few of them at a time, in clusters which move erratically on the page. Where they are not seen, the grey alleys seem to be continuous, generating grey crossings that are not actually present. Some black sparkling can be seen at those crossings where no disk is seen. The illusion also works in reverse contrast. PMID- 11220213 TI - Curvature biases in stereoscopic vision: a nasotemporal asymmetry. AB - The reliability of curvature judgments for linear elements was studied, with stereograms that contained a binocular arc with curvature in depth, and either a binocular frontoparallel arc or a monocular one, on a background representing a hemiellipsoid. The subjects made about 15% errors on binocular arcs with curvature in depth, and 60%-80% of these occurred when both the hemiellipsoid and the arc were convex, the arc being perceived as concave, by transparency through the hemiellipsoid. There were also about 15%-30% errors on frontoparallel arcs, but spread among all situations, with a small prevalence of concave judgments. Curvature in depth was assigned to the monocular stimuli in more than 60% of the cases. There was a curvature bias when the monocular arcs were on the nasal side, and were viewed against a concave background. Assuming parallel viewing, nasal ingoing arcs were usually perceived as concave, and nasal outgoing arcs usually perceived as convex, in agreement with geometrical likelihood. Nasal-side elements captured by one eye are, in general, those with the highest likelihood of having matching elements in the other eye. Then the observed nasal bias effect suggests that the matching process in stereopsis could be driven from the nasal sides of the projections in the two cerebral hemispheres. PMID- 11220214 TI - From image segmentation to anti-textons. AB - We apply the 'patchwork engine' (PE; van Tonder and Ejima, 2000 Neural Networks forthcoming) to encode spaces between textons in an attempt to find a suitable feature representation of anti-textons [Williams and Julesz, 1991, in Neural Networks for Perception volume 1: Human and Machine Perception Ed. H Wechsler (San Diego, CA: Academic Press); 1992, Proceedings of the National Academy of Sciences of the USA 89 6531-6534]. With computed anti-textons it is possible to show that tessellation and distribution of anti-textons can differ from that of textons depending on the ratio of texton size to anti-texton size. From this we hypothesise that variability of anti-textons can enhance texture segregation, and test our hypothesis in two psychophysical experiments. Texture segregation asymmetry is the topic of the first test. We found that targets on backgrounds with regular anti-textons segregate more strongly than on backgrounds with highly variable anti-textons. This neatly complements other explanations for texture segregation asymmetry (e.g. Rubenstein and Sagi, 1990 Journal of the Optical Society of America A 7 1632-1643). Second the relative significance of textons and anti-textons in human texture segregation is investigated for a limited set of texture patterns. Subjects consistently judged a combination of texton and anti-texton gradients as more conspicuous than texton-only gradients, and judged texton-only gradients as being more conspicuous than anti-texton-only gradients. In the absence of strong texton gradients the regularity versus irregularity of anti-textons agrees with perceived texture segregation. Using PE outputs as anti texton features thus enabled the conception of various useful tests on texture segregation. The PE is originally intended as a general image segmentation method based on symmetry axes. With this paper we therefore hope to relate anti-textons with visual processing in a wider sense. PMID- 11220215 TI - A neuro-cognitive visual system for object recognition based on testing of interactive attentional top-down hypotheses. AB - We propose an extension of a systemic model for object recognition formulated by Rybak et al (1998 Vision Research 38 2387-2400) which is based on the functional organisation of the visual systems in primate brains. In contrast to the learning and recognition scheme of Rybak et al we do not assume a behavioural paradigm, i.e. a visuomotor programmed scanpath that determines the sequence of foveation on the different parts of the object. As in the basis architecture of Rybak et al, the system modules are separated into 'what'-like subsystems corresponding to the ventral occipito-inferotemporal visual path and 'where'-like complexes analogous to the dorsal occipito-parietal visual path. The 'what' system analyses local features in the actual foveation as in Rybak et al. But, in our case, the 'where' memory, instead of programming a behavioural scanpath, scores the spatial relationship between successive fixation and the spatial relationship between the associated main edges. The recognition is based on the identification of parts and their spatial relationship. This gives the learning and recognition mechanisms more flexibility in the sense that, for recognising an object, several different fixation sequences may be accepted. PMID- 11220216 TI - The Leaning Tower of Pisa effect: an illusion mediated by colour, brightness, and motion. AB - We report a novel, easily observed, and extraordinarily striking optical illusion mediated by interactions of colour, brightness, form, and motion perception--the Leaning Tower of Pisa (LTOP) illusion. Under some circumstances, the perception of orientation of coloured forms is radically altered by rotary movement. We demonstrate that this kinetic effect--easily reproduced with a common record turntable--is optimised by particular colour and brightness differences between foreground and background with an illusory tilt of 8 degrees and more. The described illusions can be easily studied at home by downloading the colour figures from www.perceptionweb.com/perc1000/ditzinger, printing them on a common colour printer and placing them on a rotating record turntable. PMID- 11220217 TI - Medical Infobahn for Europe. Proceedings of the MIE2000 and GMDS2000 Congress. Hannover, Germany, 2000. PMID- 11220218 TI - Routine periodic acid-Schiff staining of nail plate fragments in fungal cultures for onychomycosis: a method to increase the sensitivity of diagnosis. AB - We propose the routine staining of nail plate fragments with periodic acid-Schiff stain to increase diagnostic accuracy in diagnosing onychomycosis. The advantages of this method, including increasing diagnostic yield after contaminant growth, confirmation of negative culture, and low cost, are reviewed. PMID- 11220219 TI - [Reptiles from Cerro Colorado and its surroundings, Cumana, Sucre State, Venezuela]. AB - An inventory of the reptiles that inhabit in Cerro Colorado and its surroundings, was performed from March, 1994 to March, 1995. There were reported 8 species of snakes and 7 of lizards enclosed in 4 and 5 families repectively. Aspects observed were ecolology as habitat, activity, reproduction and relative abundance. The more abundant species of lizards were: Cnemidophorus femniscatus, Ameiva bifrontata, (Teiidae), Tropidurus hispidus (Tropiduridae), Gonatodes vittatus and Hemidactylus mabouia (Gekkonidae) and the ophidians: Leptodeira annulata and Mastigodryas amarali (Colubridae). It is believed that the changes occurred in the zone influenced the increase of the relative abundance of the species Leptotyphlops goudotii (Leptotyphlopidae) arid Gymnophthalmus speciosus(Gymnophthalmidae) and perhaps in the disappearance of others that have been reported at the xerophitic or semixerophitic zones of the Sucre State of Venezuela. PMID- 11220220 TI - [Directed trees and its application to social sciences]. AB - Directed trees are special graphs usually employed as illustrative device of numerical methods applied in evolutionary biology. The present note explores its possible application in social sciences. Its utility as classificatory method in a classical anthropological study of cultural exchanges is exemplified. PMID- 11220221 TI - [Leaf anatomy study in Solanaceae of Venezuela. V. leaf anatomy of eleven species of Cestrum L] . AB - Leaf anatomy of the following eleven species: C. buxifolium Kunth, C. humboldtii Francey, C. lindenii Dunal, C. mariquitense Kunth, C. megalophyllum Dunal, C. olivaceum Francey, C. pariense Steyerm., C petiolare Kunth, C. scandans Vahl, C. strigilatum Ruiz et Pavon and C. tomentosum L.f. is described. Transverse sectioning, bruise and clearing according to the classical methods for optical microscopy were made. The species studied show dissimilitude in relation to a) fohar blade: thickness and sinuosity of epidermal cell walls; type, density and presence of trichornes, leaf type according the position of the stomata, thickness of both palisade and spongy parenchy-ma, number of spongy parenchyma layers, occurrence or not of paranchymatous sheath and sclerifled cells in mesophyll, tmbeculae or projection walls b) Midvein: degree of development and arrangement of the parenchyma and collenchyma, c) Petiole: size and form in transverse section, presence of ornamented cuticle, peridermis and degree of development of the sclerenctiyma next to vascular bundles. PMID- 11220222 TI - [Anatomic and morphological studies on the initiation of somatic embryos obtained from meristematic apexes of Musa sp. AB - The origin of somatic embryos obtained from meristematic apexes of the Musa (AAA) clone "Gran enano" was analyzed through histological and morphological studies during the various development phases of the process. The research point out that somatic embryos developed directly from perivascular parenchyma cells of the leaves. Histological sections of globular embryos showed a radial disposition to cell and the existence of an epidermal layer that surrounds the embryo completely. When citocinine (Z or BA) was added, some embryos remained in globular stage with mild signs of enlargement but with no later development of invagination. Other's embryos reached the invagination stage; and some reached the enlargement stage with active photosynthetic tissues. However there were no to generation of complete plant regardless of additional treatment, such as "osmotic shock" or the additions of GA3--At present do not have an explanations for this results. Therefore, additional experiment should be in early, intermediate and later stages of somatic embryogenesis, in order to understand the mechanisms underlying the lack of development of plants from somatics embryos. PMID- 11220223 TI - [Morphology and anatomy of the fruit development of Ocotea puberula (Rich.) Nees and Nectandra megapotamica (Spreng.) Mez (Lauraceae)]. AB - The morphology and anatomy of the fruit development of Ocotee puberula (Rich.) Nees and Nectandra megapotamica (Spreng.) Mez (Lauraceae) was studied in flowers and fruits collected in secondary forests of Maringa, Parana State, Brazil. The fruits of the species are drupes, with epidermic exocarp, parenchymatous mesocarp and endocarp which consists of macrosclereids. The origin of endocarp is the internal epidermis of ovary. The exalbuminous seeds develop from the anatropous ovules and they have testa and tegmen with parenchymatous cells frequently compressed. In the hilum region these teguments show sciereids in radial arrangement. The straight embryo has thick cotyledons which contain reserve substances such as starch and oil. The plumule and hypocotyl-radicle axis are reduced. PMID- 11220224 TI - [Massive multiplication of coffee (Coffee arabica L. cv. Catimor) through embryogenic cell suspension culture]. AB - Cell suspensions offer several advantages as a system for massive propagation because of the high rates of multiplication, the higher homogeneity in the culture conditions and the possibility of automatization. In this study, different experimental conditions were analyzed to establish embryogenic cell suspension cultures of coffee. The best conditions to establish the embryogenic cell suspension cultures of coffee were as follows: coffee leaf sections were cultivated during 12 weeks (Stage I) in a solid medium with the Murashige and Skoog salts, 2 mg/l kinetin and 0.5 mg/l 2,4-dichlorophenoxiacetic acid (medium 1). Under these conditions the explants formed a callus tissue that was transferred to a liquid medium containing 5 mg/l of 6-benzylamlno-purine (medium 2). After 12 days in a shaking liquid medium (Stage II), the cultures were sieved and were maintained In the same media, which was renewed every eight days (Stage III). This method yielded 1884 embryos in 50 ml; placing the embryos under conditions for germination yielded plantlets of normal appearance. PMID- 11220225 TI - [Spatial and temporal variation of the fish community inhabiting the Laguna Grande de Obispo, Gulf of Cariaco, Sucre State, Venezuela]. AB - The monthly species composition and the spatial and temporal variation of fish community of Laguna Grande de Obispo, Gulf of Canaco, Sucre State, Venezuela were analyzed. The samples were collected using two beach seines of different size from December 1995 to November 1996. A cluster analysis for stations inside the lagoon and time of capture showed 4 major groups, defined principally with ecological parameters of each area. Fishing with large seine in and outside the lagoon showed two large groups which were divided into 10 subgroups in function of station and time, while an inverse analysis of the same sample differentiated into 8 groups of species. based on distribution, dominance, and occurrence. Xenomeianiris brasiliensis, Mugil curema and Eucinostomus argenteus were the most abundant species in both time and space. An analysis of conglomerate on the whole fish community of the sampling period indicated the existence of two groups: i) the first half of the year including December 1995 and October 1996 and ii) the second half of the year. The distribution of fishes in relation to ecological factors is discussed. PMID- 11220226 TI - Investigation of an outbreak of endemic coccidioidomycosis in Brazil's northeastern state of Piaui with a review of the occurrence and distribution of Coccidioides immitis in three other Brazilian states. AB - An outbreak of coccidioidomycosis is described that involved three individuals and eight of their dogs, who had engaged in a successful hunt for nine-banded armadillos (Dasypus novemcinctus) in the environs of Oeiras, a community in Brazil's north eastern state of Piaui. Diagnosis was based on clinical, serological and cultural findings. Four of 24 soil samples collected in and around the burrow of an armadillo yielded cultures of Coccidioides immitis, thus establishing the endemicity of that mould in the state of Piaui. A literature review revealed that C. immitis, aside from that state, is endemic in three other Brazilian states--Bahia, Ceara and Maranhao. These four contiguous states have semi-arid regions where climatic conditions and their flora are similar to those that exist in C. immitis's endemic regions in North, Central and South America. PMID- 11220227 TI - Leprosy research at the new millennium. Proceedings of a workshop. 26-28 June 2000. Paris, France. PMID- 11220229 TI - Absolute income and life expectancy. PMID- 11220228 TI - Proceedings of the European Society of Surgery 4th Annual Meeting. Krakow, December 3-6, 2000. PMID- 11220231 TI - [News from the HAUTARZT to the dermatologist]. PMID- 11220230 TI - Fractured neck of the femur in the elderly patient. PMID- 11220232 TI - [Recommendations for carrying out quality assurance in dermatological histology. Recommendations of the Working Group "Quality Assurance in Dermatological Histology" of the Committee for Dermatological Histology (ADH) of the DDG]. PMID- 11220233 TI - [Epiluminescent microscopy aspects of initial cutaneous melanoma metastases]. AB - BACKGROUND AND OBJECTIVE: Especially small and initial cutaneous melanoma metastases (CMMs) are tumours with inconspicuous clinical and sometimes histological features which may be difficult to differentiate from other melanocytic lesions. The present study was performed to determine whether epiluminescence microscopic (ELM) criteria could increase the accuracy in preoperative evaluation of CMMs. PATIENTS/METHODS: Thirty photographed and histologically verified CMMs were examined retrospectively using ELM in order to visualize a multitude of morphological features permitting the recognition of malignancy. The colour slides obtained by the photography were subjected to a secondary 30-80 fold magnification in order to conduct a visual analysis. The 50 naevi in the control group were all histologically benign. RESULTS: Five of the 15 features studied were shown to differ significantly between the two groups. Polymorphic angiectatic base pattern and vascular aneurysms, areas of polymorphic and horizontally dilated capillaries, peripheral erythema, saccular pattern and a light brown halo had a specificity of 90-98% and a sensitivity of 40-46% for CMMs (p<0.001). Peripheral grayish patches, lesions surrounded by gray streaks and microscopic ovoid blood lakes were absent in the benign group. CONCLUSIONS: The prevalence of distinct ELM criteria in CMMs enhances the diagnostic accuracy of malignancy in melanocytic skin lesions. PMID- 11220234 TI - [Evaluation of a telemedicine pilot project]. AB - BACKGROUND AND OBJECTIVE: Rapid progress in computer and information technologies has led to an increased interest in the use of telemedicine during the past few years. Thus it should be clarified, whether teledermatology can achieve comparable results to conventional specialist examination and advice. PATIENTS/METHODS: We initiated a pilot study, comparing teledermatology with conventional examination in a dermatology outpatient setting. 60 patients were included. RESULTS: Out of 60 teledermatological examinations, remote clinicians were in agreement with face-to-face clinicians in 90%. Teledermatology was unable to make a useful diagnosis in 6 patients, however further diagnostic procedures were ordered, enabling teledermatologists to achieve correct diagnoses. Regarding need for further diagnostic tests, there was no difference between teledermatology and conventional examination. CONCLUSIONS: Teledermatology appears suitable to transfer a dermatologist's expertise over large distances. PMID- 11220235 TI - [Phylloid hypomelanosis and mosaic trisomy 13: a new etiologically defined neurocutaneous syndrome]. AB - The term phylloid hypomelanosis is proposed to denote a new etiologically defined neurocutaneous syndrome. The hallmark of this trait is a pattern of hypopigmentation consisting of round or oval lesions, large asymmetrical areas reminiscent of the leaves of a begonia, as well as pear-shaped areas or oblong macules. The term phylloid pattern is derived from Greek phyllon=leaf and eidos=form. In 5 out of 6 cases in which cytogenetic findings were reported, a mosaic trisomy 13 or translocation trisomy 13 was found. All patients showed CNS defects with mental retardation. In addition, absence of corpus callosum, conductive hearing loss, choroidal and retinal coloboma,cranio-facial defects as well as brachydactyly,clinodactyly, camptodactyly and other skeletal anomalies were reported. In contrast to hypomelanosis of Ito which is associated with many different forms of genetic mosaicism, phylloid hypomelanosis most likely represents a cytogenetically rather uniform neurocutaneous phenotype. PMID- 11220237 TI - [Molluscum contagiosum: treatment with pulsed dye laser]. AB - BACKGROUND AND OBJECTIVE: There is a wide variety of methods for the treatment of mollusca contagiosa. Especially with anxious children, most of them are not applicable because they are often invasive, painful, time intensive or difficult to conduct (e.g. if a stay in hospital is necessary). In order to verify the existing case reports, this paper evaluates the application of the pulsed dye laser as a possible therapy alternative in cases of mollusca contagiosa. PATIENTS/METHODS: In a prospective study 20 patients with mollusca contagiosa were treated with the pulsed dye laser. RESULTS: The therapy was well tolerated; no scars or pigment anomalies were observed. 95.9% of the lesions healed after the first treatment, the other 4.1% after the second. This larger study verifies the positive findings indicated in case studies. CONCLUSIONS: For exposed sites, difficult cases or if other treatment methods have failed, the pulsed dye laser is an effective, quick, bloodless and elegant therapeutic alternative for mollusca contagiosa with a low rate of side effects. PMID- 11220236 TI - [Treatment of endemic scabies with allethrin, permethrin and ivermectin. Evaluation of a treatment strategy]. AB - BACKGROUND AND OBJECTIVE: Ectoparasitic cutaneous infestations are still common problems in countries of Western Europe. Scabies is a highly contagious disease of the skin caused by Sarcoptes scabiei variatio hominis. It has a world-wide distribution and affects all ages with no specific gender predisposition. Scabies is of profound public health interest because certain environment factors such as overcrowding, poor hygiene, delayed treatment of primary cases and lack of public enlightenment are conducive to its spread. However, prompt and adequate therapy is rewarding and prevents further spreading. Scabies acquires additional public health significance when large numbers of individuals are affected, as in a nursing home. Outbreaks of scabies in such dimensions require a special treatment strategy. PATIENTS/METHODS: On request of the town council an eradication concept for the treatment of endemic scabies in nursing and retirement homes was developed. RESULTS: persons (IP) and identification of the likely index patients (IXP)because of their widespread disease should be the first step of an eradication program. All IP except for IXP should be treated irrespective of clinical signs by a single application of a modern effective external scabicide such as allethrin (Spregal) or permethrin cream (permethrin 2,5% until 6th year of life or permethrin 5% in a hydrophilic cream) at day 1 (day X). The following 10-day quarantine and close control of all IP is an inexpensive and safe method of eradication. IXP are admitted and treated with oral administration of single dose of ivermectin, which can be repeated on day 8 if necessary. In addition permethrin cream 5% can be applied in severe cases, combined with nail trimming and aggressive cleaning of the subungual debris. Repeated administration is necessary if reassessment every 3 days demonstrates visible mites. (Note: none of this is mentioned in German.) The staff is instructed to wear gloves during all patient contact. CONCLUSIONS: Our strategy for eradication of endemic scabies has proven effective. Allethrin can be used following the package inpermethrin is more effective and can also be used in children, as well as pregnant and nursing women. Ivermectin is particularly useful in treating crusted scabies. It is not approved for scabies in Germany so the patients must be accordingly counseled. The frequency and the major therapeutic problems in treating endemic scabies make it important to work for the approval of permethrin and ivermectin in this setting. PMID- 11220238 TI - [Multiple mantleomas in Birt-Hogg-Dube syndrome: successful therapy with CO2 laser]. AB - Birt-Hogg-Dube-syndrome, first described 20 years ago, is an autosomal dominant inherited disease, characterized by the occurrence of multiple cutaneous hamartomas with adnexal differentiation. An association with intestinal neoplasms has been mentioned repeatedly. Recently, the cutaneous lesions in this syndrome have been interpreted as different developmental stages of one single hamartoma with sebaceous differentiation, called mantleoma. Numerous dermatohistopathologic studies contribute to the certain diagnosis of Birt-Hogg-Dube-syndrome. In contrast, little information is available on the therapy of the multiple skin lesions. A father and his daughter with Birt-Hogg-Dube-syndrome were treated with the CO2 laser, producing satisfactory results. PMID- 11220239 TI - [Pyoderma gangrenosum: successful topical therapy with tacrolimus (FK506)]. AB - Pyoderma gangrenosum is a distinct clinical entity characterized by chronic, recurring, destructive ulcerations. Although the pathogenesis of pyoderma gangrenosum is unknown, immunologic aberrations of neutrophil granulocytes seem to be important. Systemic steroids and macrolide lactones such as cyclosporin A and tacrolimus have been reported to be useful in the clinical management of disease. Pyoderma gangrenosum has been found to be associated with several systemic diseases. The association with chronic ulcerative colitis is well known, but the diagnosis may be complicated by early administration of systemic steroids. Therefore, local immunosuppression with topically applied agents could be an efficient therapeutic alternative especially for mild or early cutaneous lesions.We describe the successful topical treatment of a patient with multiple lesions of pyoderma gangrenosum with 0,1% tacrolimus (FK506) ointment which is known to have better dermal penetration and higher immunosuppressive potency than topical cyclosporin A. In addition, other indications for topical tacrolimus are discussed. PMID- 11220240 TI - [Trichorhinophalangeal syndrome. Case report and biophysical study of hair shaft parameters]. AB - In 1956 Klingmuller first described the trichorhinophalangeal syndrome (TRPS), which was named by Giedion ten years later. The syndrome includes a combination of typical hair, facial and bone abnormalities with variable expression allowing the further distinction of three subtypes. In a 37-year old patient with TRPS type I who reportedly had reduced hair growth length, clinically fine and brittle hair were found. Scanning electron microscopy revealed widely spaced cuticular scales. Quantitative measurement of the biomechanical properties of the hair showed a significant increase in the viscous parameter. This could be a result of decreased disulfide bridges and increased halogen bonds in the keratin matrix of the hair. In dermatological practice patients with TRPS often present because of hair abnormalities. Because of premature arthrosis due to skeletal abnormalities, occupational counseling is advised.Congenital heart problems, kidney abnormalities and endocrinological problems are rare, but should be sought in the symptomatic individual. Apart from mild hair care and avoidance of additional physical or chemical injuries due to hair cosmetic procedures,there is no treatment for the hair defects. PMID- 11220241 TI - [Bullous scabies and scabies-triggered bullous pemphigoid]. AB - Two patients were admitted to our hospital with tense blisters on an erythematous base, typical for bullous pemphigoid. In both patients an infestation with Sarcoptes scabiei was diagnosed by dermatoscopy as well as histological examination. In one patient the clinical diagnosis of bullous pemphigoid could be confirmed by immunofluorescence microscopy, histopathology and a clinical relapse of bullous pemphigoid without scabies infestation. In the other patient no evidence for an autoantibody-mediated autoimmune blistering disease was found. We postulate that bullous scabies could develop after long persistency of the parasites leading to a specific immune response with activation of T helper type 2 (Th2) cells causing high levels of the cytokine interleukin 5 and then consecutively eosinophilia. Secretion of proteolytic enzymes near the basal membrane zone might explain the development of intraepidermal, often suprabasal blisters. In contrast, in the first patient the scabies infestation might have triggered a flare up of the underlying autoimmune disease. Comparison of our two patients demonstrates two entities: bullous pemphigoid triggered by scabies as a Koebner phenomenon and a bullous subtype of scabies mimicking bullous pemphigoid. Therefore both, scabies infestation triggering bullous pemphigoid and bullous pemphigoid-like scabies should be included in the differential diagnosis of vesicles, tense blisters and erythema, especially at an early clinical stage. PMID- 11220242 TI - [Clinical aspects and therapy of anogenital warts and papillomavirus-associated lesions]. AB - There is a series of different therapies for the treatment of anogenital warts. Home therapy should be reserved only for initial therapy of simple cases. Such approaches include podophyllotoxin solution, podophyllotoxin cream,imiquimod cream and adjuvant interferon gel. Recurrent disease and disseminated disease must be treated by the physician. Choice of therapy depends on the morphology, the extent of the disease and also on the immunological status of the patient. Therapy should be discussed between the physician and the patient. Whatever therapy will be chosen, HPV DNA can persist latently in surrounding tissue and may lead to recurrence of visible lesions. Long-standing warts can undergo malignant conversion; intraepithelial neoplasias such as Bowen's disease, erythroplasia of Queyrat and bowenoid papulosis are especially prone to develop into squamous-cell carcinoma. Thus adequate therapy and thorough follow-up are mandatory in such cases. In the future therapies directed against HPV specifically will be available. They should lead both to destruction and complete clearance of visible lesions and also should prevent recurrences. Ideally HPV should be eliminated completely from the treated tissue. PMID- 11220243 TI - [Inhibitory effects of sunscreens on the development of skin cancer]. PMID- 11220244 TI - [A medical student discovers onychomycosis]. AB - When G. Meissner discovered the tactile bodies of the skin, he earned early fame. Yet he made further contributions to dermatology which have been forgotten such as the first description of onychomycosis. This took place when he was still a student in Gottingen. The circumstances of this discovery are told in the context of the medical history of that time, paying special attention to certain epidemiological aspects. Finally, a detailed account is given of Meissner's academic career. PMID- 11220246 TI - [A new modern domicile for the Clinic and Polyclinic of Dermatology of the FU Berlin]. PMID- 11220245 TI - [Extensive anal ulcerations in a 19-year-old patient]. PMID- 11220247 TI - [The yeast fungus Malassezia: pathogen, pathogenesis and therapy]. PMID- 11220248 TI - [Reducing the dosage by new technology]. PMID- 11220249 TI - [Minoxidil: more than an antihypertensive]. PMID- 11220250 TI - [Proven and promising for the future]. PMID- 11220251 TI - [Quantification of blood loss. How precise is visual estimation and what does its accuracy depend on?]. AB - Estimation of blood loss is a difficult task. Apart from measuring the volume of the suctioned blood the anaesthetist has to make a visual estimate of blood shed on the floor, spread in the surgeons' gowns and gloves and hidden in drapes and sponges at nearly every operation. We were interested in how exact visual estimation of blood loss can be and what factors influence accuracy and precision of the visual estimate. In one OR we simulated typical blood loss scenes occurring during a mock hip joint replacement, using our normal customary equipment of drapes, sponges and containers. More than 8 litres of blood from autologous whole blood donations were partitioned with a graduated measure and syringes and were distributed around the OR in 22 locations in typical ways. 36 members of staff entered the OR one by one and all gave their 22 estimates. Results were analysed by repeated measures analysis of variance. Bias (accuracy) and variation error (precision) were calculated for individuals and groups of individuals. We found a broad deviation of the visual estimates and little coincidence with the actual values. Over- and underestimations by 2 or even 3 were rather common; underestimations were more frequent. We found a significant trend to overestimate diluted blood, even though these certain sites were known to exhibit diluted blood. On the other hand laparotomy pads and sponges fully saturated with blood as well as the simulation of the operative site were grossly underestimated. Age, sex and professional experience (!) did not influence the magnitude of estimation errors, but the professional groups'estimates differed: anaesthetists estimated slightly but significantly more than orthopedic or general surgeons. Obviously our capability to estimate lost blood volumes is more influenced by our belonging to a professional group than by our professional experience. Do we not learn by experience? Diluted blood is overestimated, whereas in some other typical scenes blood loss is grossly underestimated. Simulations such as this one may improve our estimation capabilities and thus result in better patient care in the OR. PMID- 11220252 TI - not app. PMID- 11220253 TI - [Neural networks and pain processing. New insights from imaging techniques]. AB - Imaging techniques with high spatial and temporal resolution (PET,fMRI, MEG) provide detailed information about the brains' processing of pain. Structures detected by these techniques are not understood as pain centers but as nodal points of a dynamic network which is influenced by physiological and psychological input. Imaging techniques can be used for the investigation of different pain components. The neuronal network that encodes sensory discriminative information consists of the primary and secondary somatosensory cortex which receive input from lateral thalamic nuclei. Information for the affective pain component reach the anterior cingulate cortex, insula and prefrontal cortex via medial thalamic nuclei. Until now only little is known about cortical structures mediating the cognitive pain component. In chronic pain the cortical and subcortical processing of nociceptive input is presumably modified. Reorganization in the primary somatosensory cortex is presented as an example of neuronal plasticity induced by chronic pain. PMID- 11220254 TI - [Cardiovascular stress protection following anesthesia induction. Comparison of clonidine and esmolol]. AB - Alpha-2-adrenoceptor-agonists as well as cardioselective betareceptor-antagonists have been shown to blunt stress response due to tracheal intubation. The purpose of our study was to investigate,whether clonidine or esmolol is more efficient to attenuate stress response due to intubation.44 patients were randomly assigned to receive either clonidine (n=22; 3 microg/kg) or esmolol (n=22; 2 mg/kg) immediately prior to a standardized induction of anaesthesia. Heart rate, arterial blood pressure, cardiac output, epinephrine and norepinephrine plasma concentrations were measured before,during and 10 min after intubation. Blood pressure was measured invasively and cardiac output was determined by transthoracic echocardiography. Absolute values and increase of mean arterial pressure and norepinephrine plasma concentrations were significantly less in the clonidine group (p<0,05). Clonidine (3 microg/kg) is more efficient than esmolol (2 mg/kg) in blunting stress response due to endotracheal intubation. PMID- 11220255 TI - [Danaparoid (Orgaran) as an antiocoagulant for mechanical autotransfusion with Cell Saver 5 (Hemonetics)]. AB - We investigated Danaparoid Sodium (Orgaran) as anticoagulant using three different concentrations (9, 4,5 or 3 U/ml anticoagulant solution) for the use in the autotransfusion device Cell Saver 5 (Haemonetics). Fresh units of whole blood packs were mixed in the reservoir in a proportion of 5:1 with the anticoagulant solution. Having started the Cell Saver 5 in the automatic mode, the amount of Danaparoid in the retransfusion blood was determined (chromogenic Antifactor-Xa test). The lowest concentration of the anticoagulant was applied in 4 patients with Heparin-induced Thrombocytopenia Type II undergoing total hip arthroplasty. There was a correlation between the concentration in the reservoir and in the retransfusion blood. None of the patients showed a disturbance of his coagulation system. One of them had slight clotting in the reservoir. We recommend the use of the lower concentrations tested: 4,5 U/ml or, particularly for patients with renal insufficiency or low body weight or expected high retransfusion volumes, 3 U/ml as anticoagulant concentrations. If the autotransfusion device is used according to the manufacturer's instructions there may be virtually no risk of clotting in the Cell Saver or of inhibition of the coagulation system in the patient. PMID- 11220256 TI - [Acute Leriche's syndrome in a patient undergoing coronary artery bypass grafting with extracorporeal circulation]. AB - We are reporting a case of an acute thromboembolic obstruction of the aortic bifurcation in a 66-year-old patient undergoing coronary artery bypass grafting with extracorporeal circulation. After declamping of the aorta, the arterial pressure measured in the femoral artery suddenly dropped, whereas the pressure measured in the aortic cannula and in both radial arteries stayed normal. Transoesophageal echocardiography was performed to exclude an acute aortic dissection. While the patient always had a constant sinus rhythm, an angiography following the end of surgery, showed a complete obstruction of the abdominal aorta. Subsequent embolectomy through bifemoral arteriotomies was performed and a histologically fresh embolus (6,5 g in weight) was extracted. Neither the pre- and intraoperative echocardiography, nor the preoperative ventriculography showed signs of an intracardiac thrombus. Insufficient anticoagulation and a lack of inhibitor potential were almost excluded. Considering the histological findings, we assumed that the embolus was formed intraoperatively. Without further complications the patient left our department on the 8th postoperative day. PMID- 11220257 TI - [Massive acute hypotonic hyperhydration following arthroscopic synovectomy]. AB - We report the case of a 4 year old boy who developed a massive water intoxication as a complication during knee arthroscopy. The sodium plasma concentration dropped to 100 mmol/l postoperatively. This complication may be triggered by prolonged surgery time, excessive intra-articular pressure, capsular tears and low body weight. To prevent massive incorporation of hypoosmolar fluid, the inflation of a tourniquet as well as the use of NaCl 0,9% as irrigation fluid seems to be of advantage. The guidelines for replacing sodium in hyponatremia are discussed according to literature. In general, hyponatremia should be corrected in the same amount of time as it took for it to develop. PMID- 11220258 TI - [Epileptoform EEG activity: occurrence under sevoflurane and not during propofol application]. AB - In a 62-year-old female patient without a history of epileptic seizures EEG monitoring (EEG monitor: Narcotrend) was routinely performed during propofol/remifentanil and during sevoflurane/remifentanil/nitrous oxide anaesthesia. In the first course of anaesthesia after a bolus of propofol 1% a continuous EEG slowing was followed by a burst suppression pattern without occurrence of epileptiform activity throughout this sequence. During the second course of anaesthesia the sevoflurane concentration was increased from 2 to 8 % by volume. After 5 min epileptiform activity appeared in the EEG at an endtidal concentration of 5.9% by volume. PMID- 11220259 TI - [Nosocomial pneumonia. Epidemiology, pathogenesis and diagnosis]. PMID- 11220260 TI - [Intrascalene block]. PMID- 11220262 TI - [New diagnostic possibilities and macular diseases]. PMID- 11220261 TI - [Colloids in intensive care]. PMID- 11220263 TI - [Autofluorescence imaging of the macula]. AB - Visualization of the retinal pigment epithelium (RPE) in vivo has proven difficult for various reasons, including the optical properties of the eye and the small size of the cellular elements, forming a single layer between the neurosensory retina and Bruch's membrane. With the advent of scanning laser ophthalmoscopy it is now possible to image topographic distribution and intensity fundus autofluorescence derived from accumulations of lipofuscin granules in RPE cells. Excessive lipofuscin storage in the RPE cytoplasm occurs not only in association with age but also with many hereditary and degenerative retinal diseases including age-related macular degeneration, Stargardt disease, Best disease, and pattern dystrophies. Lipofuscin in the RPE derives mainly from incomplete degradation of phagocytosed distal segments of photoreceptor outer segments, and is composed of various biomolecules including lipids, protein, and retinoids. Some of its constituents have recently been shown to possess toxic properties in vitro and may play a pathophysiological role in diseases such as age-related macular degeneration.Visualizing lipofuscin in vivo may help to better understand the significance of these metabolic alterations in the pathogenesis of retinal disorders. In addition,fundus autofluorescence imaging can be useful in the preclinical diagnosis of hereditary retinal disease. Dynamic alterations of intrinsic RPE fluorescence change may be applicable for monitoring effects at the level of the RPE of novel therapeutic modalities. Furthermore, identification of high-risk characteristics in patients with age-related macular degeneration with this technique may be helpful for indicating and adjusting future therapies. PMID- 11220264 TI - [Bilateral progressive choroid neovascularization in a 38-year-old patient. Ocular histoplasmosis syndrome]. PMID- 11220266 TI - [Multifocal electroretinography in diagnosis of macular diseases]. PMID- 11220265 TI - [Neuroprotection in retinal diseases. Myth or reality?]. PMID- 11220268 TI - [Fundus-controlled functional evaluation in macular diseases with the scanning laser ophthalmoscope]. AB - Exact functional testing in macular diseases still presents a challenge for the ophthalmologist in detecting both small (para)central scotomas and changes in fixation habits. The recent development of scanning laser ophthalmoscopy has enabled functional testing with simultaneous observation of the fundus. In addition to automatic static threshold fundus perimetry, kinetic fundus controlled perimetry and special fixation tasks can be applied. This method also allows the examination of reading performance combined with the exact observation of fixation and has been increasingly integrated into clinical routine. This allows more exact observations concerning macular function for diagnostic purposes, in evaluating new treatment methods, and as expertises in simulation or aggravation in patients with macular diseases. PMID- 11220267 TI - [Optical coherence tomography]. AB - Optical coherence tomography has become an established method for imaging retinal diseases. It is now an accepted method for making quantitative measurements in studies on the cause and course of macular holes, vitreoretinal traction, pigment epithelial detachment, macular edema, and diabetic retinopathy. Its potential benefit in the evaluation of age-related macular degeneration and a variety of other diseases is currently under investigation. In clinical practice optical coherence tomography images add information to the biomicroscopic findings and results of other imaging techniques or functional testing and can significantly help in making critical decisions. Its future role in routine clinical practice will depend on further technical development and the results of long-term studies. PMID- 11220269 TI - [Erbium:YAG laser vitrectomy. Initial clinical results]. AB - BACKGROUND: Much interest has been expressed in recent years in the use of erbium:YAG lasers in ophthalmology, particularly for vitrectomy and phacoemulsification. PATIENTS AND METHODS: We performed 54 operations (49 primary, 5 secondary) for pars plana vitrectomy on 53 eyes of 53 patients using the Phacolase erbium:YAG laser at a frequency of 10-100 Hz single-pulse energy of 5-50 mJ. RESULTS: The operation was successful in 51 cases,while in three we had to resort to mechanical vitrectomy due to initial technical problems. CONCLUSION: Erbium:YAG laser vitrectomy was generally fast and caused little mechanical stress to the retina. Complications were only those known from mechanical vitrectomy.The handpiece showed good properties for removing vitreous but not for cutting membranes, although new handpieces specifically for the cutting of membranes are under development. PMID- 11220270 TI - [Retinal nerve fiber layer thickness and peripapillary blood flow in glaucoma patients and healthy probands]. AB - BACKGROUND: In progressive glaucoma there is increasing loss of retinal nerve fibers and therefore decreasing nerve fiber layer thickness. As measurements of capillary blood flow have been reported to depend on nerve fiber layer thickness, this could result in incorrectly high blood flow measurements in patients with advanced glaucoma. METHODS: In 33 healthy controls and 59 glaucoma patients we measured retinal nerve fiber layer thickness by laser polarimetry and relative capillary blood flow by scanning laser doppler flowmetry three times on the nasal and temporal peripapillary retina. For statistical analysis a regression analysis was used. RESULTS: The correlation coefficients for volume, velocity, and flow with nerve fiber layer thickness at the same location were 0.02/-0.03/-0.02 in the temporal retina and -0.22/-0.07/-0.19 in the nasal retina (all correlations nonsignificant). CONCLUSION: No correlation was found between nerve fiber layer thickness and capillary blood flow. Measurement of capillary blood flow in glaucoma patients thus does not appear to be affected by decreasing nerve fiber layer thickness. PMID- 11220271 TI - [Laser flare in combined cataract and glaucoma surgery]. AB - BACKGROUND: We used a laser-flare meter to compare inflammation of the anterior chamber in combined cataract and glaucoma surgery with that in pure filtering surgery. MATERIALS AND METHODS: In 34 consecutive patients with primary chronic open-angle glaucoma (PCOG) we combined glaucoma surgery and cataract extraction with phacoemulsification and implantation of a foldable intraocular lens via the same incision. We compared the results with those in 32 PCOG patients receiving a single goniotrephination and in 45 PCOG patients receiving cataract extraction via clear cornea with implantation of a foldable lens. RESULTS: The increase in the flare in the first 2 days was significant in those receiving combined cataract and glaucoma surgery and in those receiving single goniotrephination but not in those receiving a single cataract extraction. After 3 weeks there was no significant difference to the preoperative value in any of the groups. The highest flare values were in patients after combined surgery, significantly higher than after cataract extraction in the first days and higher than in the goniotrephination patients 3 weeks after the operation. CONCLUSION: The highest flare on the first day was in combined cataract and glaucoma surgery. This may explain the more frequent scarring of the filtering bleb in combined surgery. Postoperatively the intraocular pressure and number of drugs used for glaucoma did not differ in patients with combined and single goniotrephination. PMID- 11220272 TI - [Modeling corneal topography with a subdivision scheme in keratoconus]. AB - BACKGROUND: Videokeratoscopy is often unable to obtain complete data sets in cases of irregular or asymmetric corneal topography. Subdivision schemes are very common in computer graphics for completion and smoothing of surfaces. Based on a network of triangular facets a smooth and complete surface in a standard coordinate system can be derived from topographic raw data. PATIENTS AND METHODS: We examined 88 patients with keratoconus and 40 normal controls. Polygons and polyhedra were defined from videokeratoscopic height data, and a surface was modeled using a modified butterfly subdivision scheme for a nonuniform sampled grid. To assess the model quality topographic raw data were changed to missing values centrally (at the apex of the cone) and in four midperipheral quadrants. The target value was the root mean square error, comparing the remodeled value of the subdivision scheme to the raw data at the position of the missing values for each group. RESULTS: Due to the nonuniform mesh of our Placido-based topographer we used a dynamic adaptive model and the governing dynamic differential equation. With a single missing value, no difference was detected between normals and patients with keratoconus. For a missing area consisting of 13 raw data points, the remodeling error was significantly higher in patients with keratoconus than in normals. With the neighborhood of 13 missing data points, the apex of the cone was remodeled in both groups of patients with less precision than with the peripheral missing data. CONCLUSION: The locality of the equation systems to be solved and the easy calculation of explicit formulas for the normals may simplify ray-tracing techniques and make subdivision attractive for large datasets in corneal topography even with irregular patterns. PMID- 11220273 TI - [Photorefractive/photo-astigmatic refractive keratectomy in low myopia and myopic astigmatism. Broad beam versus scanning spot laser technology]. AB - PURPOSE: The results of photorefractive/photoastigmatic refractive keratectomy (PRK/PARK) were compared between two patient groups treated consecutively with either broad-beam or scanning-spot technology. PATIENTS AND METHODS: PRK/PARK was performed with a broad-beam excimer laser VISX 20/20 in 46 eyes and with the scanning-spot laser system Keracor 217 in 49 eyes. Preoperative spherical equivalent (subjective manifest refraction) was < or =-6.0 diopter in both groups. Safety, efficacy, predictability, stability, and complications were investigated after 1,4 and 12, months postoperatively. RESULTS: In the broad-beam laser group no eye lost two or more lines of best-corrected visual acuity;in the scanning-spot laser group one eye lost two lines 12 months postoperatively. Efficacy, predictability, and stability were comparable between the two groups. CONCLUSIONS: Both the broad-beam and the scanning-spot laser provided good results after PRK/PARK for low myopia and myopic astigmatism. This study found no fundamental differences between the two laser systems. PMID- 11220274 TI - [The efferent lacrimal ducts of the human. Morphological and biochemical studies]. AB - PURPOSE: Infections occur frequently in the region of the efferent tear ducts. Exact knowledge of the anatomical structure and of cellular defense mechanisms is necessary to understand the pathological processes. This study analyzed the efferent tear ducts with regard to physiological function and possible defense mechanism against infections. MATERIALS AND METHODS: We used histological, immunohistochemical and electronmicroscopic techniques to investigate the lacrimal systems from 31 body donors aged 54-88 years. RESULTS: The efferent tear ducts are lined by a double-layered epithelium resting on a broad basement membrane. These cells contain many lipid droplets and secretory vacuoles in their apical part. Inside the epithelium cells are arranged partly in cell groups forming mucous glands, which morphologically resemble goblet cells of the tarsus palpebrae. The secretory products of these cells contain various carbohydrates including sialic acid. Lymphocytes and macrophages are found in the submucosa partly penetrating the epithelium. CONCLUSIONS: Lipids and mucins of epithelial and goblet cells form a specialized protective layer on the epithelium of the tear ducts which enables easy drainage of tear fluid into the inferior meatus of the nose. Together with immunocompetent cells the protective layer prevents invasion of pathogenetic agents. PMID- 11220275 TI - [Rehabilitation of anophthalmic patients. Results of a survey]. AB - BACKGROUND: We surveyed ocularists' views on orbital implants, secondary surgical procedures, patient satisfaction, and cooperation between ophthalmologists and ocularists. METHOD: A 14-item questionnaire was sent to all 29 ocularists working in Germany all 4 in the Netherlands. RESULTS: Primary implants are generally recommended, preferably dermofat grafts and ,,baseball" implants. Outcome depends crucially upon surgical procedure and postoperative course. Scepticism is common toward secondary surgical procedures, with the success rate estimated at 70%. Cooperation between ocularists and ophthalmologists is generally regarded as unsatisfactory, also the information provided to the patients by the ophthalmologist after enucleation. CONCLUSIONS: The ocularists demand best possible enucleation techniques including the use of primary implants. However, they are critical toward secondary procedures for correcting postenucleation socket syndrome. Cooperation between ocularists and ophthalmologists need to be improved in providing patient care. PMID- 11220276 TI - [Electrophysiological studies in breast carcinoma patients with tamoxifen retinopathy]. AB - PURPOSE: Crystalline plaques in the cornea or the retinal nerve fiber layer are well-known side effects of tamoxifen therapy. We investigated whether electrophysiological methods for determining the function of the retinal nerve fiber layer and retinal pigment epithelium demonstrate changes in tamoxifen retinopathy. PATIENTS AND METHODS: We compared the right eyes of four women with breast cancer and mono- or bilateral tamoxifen retinopathy to ten right eyes of age-matched, eyehealthy patients who had not received tamoxifen by means of electrophysiological investigations (e.g., pattern-reversal electroretinography, flash electroretinography for the maximal combined response, electrooculography; ISCEV standard conditions). RESULTS: No significant differences were observed between patients with tamoxifen retinopathy and controls regarding mean visual acuity, basal level of the electro-oculographic standing potential, basal level on the Arden index, or any of the other electrophysiological potentials. CONCLUSIONS: Pattern-reversal electroretinographic measurements revealed no damage of retinal ganglion cells in the presence of crystalline plaques in the retinal nerve fiber layer. Electro-oculography did reveal differences, but these were not statistically significant, possibly due to the small number of cases. PMID- 11220277 TI - [Dynamic MRI imaging of orbital diseases and ocular motility disorders]. AB - High temporal and spatial resolution has recently been achieved by rapid magnetic resonance imaging techniques. This offers the opportunity to perform dynamic magnetic resonance imaging in addition to topographic imaging and tissue analysis. Using sequences obtained by turbo-fast low-angle shot imaging we have reduced temporal resolution to 1 s per image. PMID- 11220278 TI - [3-D ultrasound. Initial experiences in various eye diseases]. AB - BACKGROUND: Studies have confirmed three-dimensional (3-D) ultrasound as a practical diagnostic tool in examining the eye and orbit and suggest its routine clinical use. MATERIALS AND METHODS: 3-D ultrasound was prospectively performed in 46 patients (46 eyes) with various ocular diseases. In six large choroidal melanomas the tumor volume were measured by 3-D ultrasound and compared to that measured by MRI and to that calculated by a theoretical formula. To assess the reproducibility of volumetry by 3-D ultrasound the volumes of such three intraocular tumors were measured ten times using ten different virtual sectioning planes and a section thickness of 0.5 mm and/or 1.0 mm. RESULTS: 3-D ultrasound allows the precise assessment of complex three-dimensional structures. Choroidal melanoma volumes measured by 3-D ultrasound, MRI, and theoretical calculation were in the same range. CONCLUSION: Intraocular tumor volume can be measured well by 3-D ultrasound,which may be of clinical importance in follow-up examinations. PMID- 11220279 TI - [Implant in Schlemm's canal. A new method for regulating intraocular pressure in patients with primary open-angle glaucoma?]. AB - BACKGROUND: A surgical technique was developed using a Schlemm's canal implant to bypass the obstruction of outflow of the juxtacanalicular trabecular meshwork in patients with primary open-angle glaucoma. The implant device should also bridge healing processes after trabeculotomy and laser techniques. PATIENTS AND METHODS: An 8- to 15-mm-long silicone tube was implanted in each of two human autopsy eyes connecting the anterior chamber directly with Schlemm's canal. Serial sectioning was performed at two sections of 1-mm length. RESULTS: Implantation of the tube was technically uneventful. Histological examination showed no evidence of mechanical disruption of the endothelial lining of the inner wall of Schlemm's canal. CONCLUSION: These preliminary results demonstrate the possibility of shunting aqueous directly into Schlemm's canal using a silicone tube. A clinical study in a selected group of patients is planned. PMID- 11220280 TI - [Accommodative lens implant]. AB - PROBLEM: To date, approaches to restore accommodation following cataract surgery have been based on the principle of a liquid or solid implant that moves within the capsular bag and thereby changes the optical characteristics of the eye. However, these implants have been associated with shrinking and fibrosis of the capsular bag, a problem that will not be solved in the foreseeable future. APPROACH: If accommodation is effected by shifting the whole capsule including its contents on the optical axis, capsular fibrosis will virtually no longer play a role. In order to execute this shift via the neuronal feedback mechanisms of the ciliary muscle in a controlled way, radial zonular forces or movements must be transformed into axial ones, which is possible by means of tiny permanent magnets. This paper describes the basic aspects of such an implant. The dependence of accommodation on all relevant parameters is quantified in a computer simulation. CONCLUSION: The implant described appears to be practicable with justifiable technical and surgical efforts. PMID- 11220281 TI - Relative Lewis basicities of six AI(ORF)4- superweak anions and the structures of LiA. AB - The relative Lewis basicities of six Al(ORF)4- ions, Al[OC(CH3)(CF3)2]4-, Al(OC(CF3)3]4-, Al(OCPh(CF3)2]4-, Al[OC[4-C6H4(tBu)](CF3)2]4-, Al(OC(Cy)(CF3)2]4 , and Al(OCPh2(CF3)]4-, have been determined by measuring their relative coordinating abilities towards Li+ in dichloromethane. The relative Li- Lewis basicities of the Al(ORF)4- ions are linearly related to the aqueous pKa values of the corresponding parent HORF fluoroalcohols. The Lewis basicity of Al[OCH(CF3)2]4- could not be measured because two of these anions can coordinate to one Li+ cation. The structures of LiAl[OCH(CF3)2]4 and [1-Et-3-Me-1,3 C3H3N2][Li[Al[OCH(CF3)2)4]2] were determined. PMID- 11220282 TI - Biotransformation of diterpenes and diterpene derivatives by Beauveria bassiana ATCC 7159. AB - The biohydroxylation of stemodin and stemodinone by Beauveria bassiana ATCC 7159 gave exclusively 2alpha,13,18-trihydroxystemodane and 13,18-dihydroxystemodan-2 one respectively. Stemarin was converted to the novel 1beta,13,19 trihydroxystemarane and 13-hydroxystemarane-19-carboxylic acid. The synthesis and biotransformation of various derivatives of stemodin have also been studied. PMID- 11220283 TI - Insulin resistance: the fundamental trigger of type 2 diabetes. AB - Type 2 diabetes is a heterogeneous condition that is not attributable to a single pathophysiological mechanism. In general, both insulin resistance and impaired insulin secretion are required for the disease to become manifest. Thus, as long as the pancreatic beta cells can compensate for the degree of insulin resistance, glucose tolerance remains normal. Clustering of type 2 diabetes in certain families and ethnic populations points to a strong genetic background for the disease. However, environmental factors such as obesity and a sedentary lifestyle are usually required to unmask the genes. Impaired insulin-stimulated glucose metabolism (particularly non-oxidative) in skeletal muscle represents a key feature of type 2 diabetes and is observed early in the pre-diabetic state. It is not clear, though, whether this represents an inherited defect in muscle or whether it develops secondarily, for example, to abdominal obesity. In favour of the latter hypothesis are findings that abdominal obesity and a low metabolic rate seem to precede the development of insulin resistance in offspring of type 2 diabetic patients. According to the thrifty gene hypothesis, individuals living in an environment with an unstable food supply could increase their probability of survival if they could maximize storage of surplus energy, for instance, as abdominal fat. Exposing this energy-storing genotype to the abundance of food typical of westernized societies is detrimental, causing insulin resistance and, subsequently, type 2 diabetes. There are a number of potential thrifty genes, including those that regulate lipolysis or code for the beta3-adrenergic receptor, the hormone-sensitive lipase, and lipoprotein lipase. Type 2 diabetes develops as a consequence of a collision between thrifty genes and a hostile affluent environment. Insulin resistance is a key trigger for the disease, and optimal management of type 2 diabetes should therefore aim to ameliorate insulin resistance early. PMID- 11220284 TI - The association between insulin resistance and endotheliopathy. AB - Vascular endothelium is involved in the regulation of vascular tone, vessel permeability, and angiogenesis. Vessel tone is determined by the balance of various paracrine vasodilatory and vasoconstrictor factors, most notably nitric oxide (NO) and endothelin-1. Not surprisingly, endothelial dysfunction is believed to be crucial in the development of the chronic vascular complications of diabetes. Endothelial dysfunction, which may be examined by studying endothelial-dependent vasodilatation in humans, is also disturbed by many of the individual features of the insulin resistance syndrome including hypertension, dyslipidaemia, and hyperglycaemia. Therefore, it may be possible that endothelial dysfunction could be closely associated with, or even a common antecedent of, the insulin resistance syndrome (IRS). There is emerging evidence that impaired endothelial-dependent vasodilatation is present in populations at future risk of diabetes and even in children of low birth weight, who may exhibit features of the insulin resistance syndrome in later life. Endothelial dysfunction is an obvious therapeutic target if the vascular pathology associated with insulin resistance and type 2 diabetes is to be ameliorated. PMID- 11220285 TI - Insulin resistance: an independent risk factor for cardiovascular disease? AB - Population-based studies have shown that patients with type 2 diabetes have a higher cardiovascular morbidity and mortality and an increased all-cause mortality compared with non-diabetic subjects. In non-diabetic subjects, hyperinsulinaemia not only has been associated with an increased cardiovascular risk, but is also related with a number of other cardiovascular risk factors- hyperglycaemia, hypertension, dyslipidaemia, and a central body fat distribution- that constitute the insulin resistance syndrome and are also characteristic of type 2 diabetes. After 23 years of follow-up in the Paris Prospective Study, both fasting and 2-h insulin concentrations were related with all-cause mortality in a U-shaped fashion, with low and high concentrations being associated with an increased risk, independently of other risk factors; in contrast, while high insulin levels carried an increased risk for cardiovascular and coronary heart disease mortality, this was not independent of other risk factors. PMID- 11220286 TI - Effects of current therapeutic interventions on insulin resistance. AB - Although diet and exercise remain the cornerstones of type 2 diabetes therapy, attempts at lifestyle changes seldom result in the achievement of glycaemic control. As a result, the addition of pharmacological agents is usually necessary. Currently available treatment options improve glycaemic control in the short term; however, maintaining long-term glycaemic control, halting disease progression, and preventing the complications of type 2 diabetes have all proven to be elusive therapeutic goals. For more than 30 years, sulphonylureas (SUs) have been first-line therapy for the management of type 2 diabetes. These compounds control hyperglycaemia by stimulating insulin release from pancreatic beta cells, and thus their benefits are limited to patients with preserved beta cell function. Despite historic reliance on these agents to treat type 2 diabetes, long-term use of SUs may desensitize beta cells. The meglitinides (e.g. repaglinide) are a new class of non-sulphonylurea secretagogues that bind to a different receptor on the beta cell. Repaglinide has a short duration of action and may be useful for the treatment of postprandial hyperglycaemia. The biguanides (e.g. metformin) represent another class of antidiabetic agents and improve glycaemic control primarily by decreasing hepatic glucose output. Metformin and SUs provide similar glucose-lowering effects, and, in combination, may provide additional benefits in some patients. Reducing the rate of glucose absorption with alpha-glucosidase inhibitors (e.g. acarbose) has been explored as an alternative approach to the management of postprandial hyperglycaemia, but these agents do not address the primary defect in type 2 diabetes. Eventually, prolonged overproduction of insulin to compensate for hyperglycaemia leads to dramatically reduced beta-cell function, and exogenous insulin therapy is required. PMID- 11220287 TI - Promising new approaches. AB - Insulin resistance in liver and muscle tissue, together with beta-cell secretory defects, leads to overt type 2 diabetes mellitus. In the early stages of this progressive disorder, glycaemic control can be established through diet and exercise alone. Indeed, in some patients, marked weight reduction can lead to normalized fasting blood glucose. As a consequence, pharmacological approaches to weight loss have been investigated as a new option for the management of type 2 diabetes in obese patients. The serotonin- and noradrenaline-reuptake inhibitor sibutramine has emerged as the most promising agent in the treatment of obesity, although it appears to be less effective in diabetic patients than in non diabetic patients. Other weight-reducing agents of potential benefit include noradrenergic anorexiants, orlistat, leptin, and beta3-agonists. Insulin and insulin secretagogues, the oldest available antidiabetic drugs, have been used to compensate for beta-cell secretory defects in patients with type 2 diabetes. Repaglinide, a new, fast-acting insulin secretagogue with a short duration of action, reduces postprandial hyperglycaemia when taken shortly before meals. Other novel antidiabetic agents are currently under development, including pramlintide (an amylin analogue) and glucagon-like peptide. Pramlintide slows gastric emptying and delays glucose absorption, and glucagon-like peptide is the most potent endogenous stimulator of glucose-induced insulin release. Recent advances in type 2 diabetes therapy have seen the development of the thiazolidinediones (troglitazone, rosiglitazone, and pioglitazone), which improve insulin resistance in patients whose diabetes is poorly controlled by diet and exercise therapy. Thiazolidinediones bind to peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and act through a process involving gene regulation at a transcriptional level. Troglitazone, the first approved drug in the class, has been shown to decrease plasma glucose levels as monotherapy but is more effective in combination with sulphonylureas, metformin, or insulin. However, despite its generally good safety profile, troglitazone has been associated with severe idiosyncratic hepatocellular injury. There have been more than 150 spontaneous reports of serious hepatic events, including at least 25 instances in which patients died or required a liver transplant. Rosiglitazone, the most potent thiazolidinedione, is still in clinical development, as is pioglitazone. To date, rosiglitazone has been shown to have no reported cases of idiosyncratic drug reactions leading to jaundice or liver failure and no clinically significant drug interactions with cytochrome P450 3A4-metabolized drugs such as nifedipine. Although the available data for pioglitazone are limited to the results of short term studies, it is reported to be safe and well tolerated. Combination therapy is increasingly important in type 2 diabetes management following failure of monotherapy because complementary mechanisms of action of the different classes of oral agents demonstrate synergistic effects when used in combination. Oral agents may also be used as adjuncts to insulin for achieving glycaemic control. PMID- 11220290 TI - Proceedings of Worldwide Insulin Resistance Editorial Board Meeting, 14 July 1998, Stockholm, Sweden. PMID- 11220289 TI - The relation between insulin resistance and cardiovascular complications of the insulin resistance syndrome. AB - It has been known for years that cardiovascular disease frequently precedes the development of type 2 diabetes, and that atherosclerosis might not be a complication of type 2 diabetes, but rather the consequence of common genetic and environmental factors (the common soil' hypothesis). The insulin resistance syndrome (IRS) is a cluster of closely associated and interdependent abnormalities, including insulin resistance, hyperinsulinaemia, android fat distribution, progressive glucose intolerance, dyslipidaemia (increased triglycerides, decreased HDL, increased small dense LDL), increased prothrombotic and antifibrinolytic factors, and hypertension. Many of these abnormalities are risk factors for type 2 diabetes, and most of them explain the predilection for atherosclerosis to occur in conjunction with IRS. Insulin resistance is a key feature of IRS, and has been suggested to be the common pathophysiological basis of atherosclerosis and type 2 diabetes. The term 'insulin resistance' denotes resistance to insulin-mediated glucose uptake into skeletal muscle, which can be measured by the glucose clamp technique. There are, however, other less understood sites of abnormal insulin action that may also be relevant in IRS. These include liver, adipose, and kidney tissue, and systems such as muscle perfusion, antilipolysis, lipoprotein lipase activity, and cation transport. The development of clinical cardiovascular end-points in a patient with insulin resistance is complex, as it includes the degree of the defect, its associated abnormalities, its consequences, and the ability to compensate for the underlying defect. It is therefore more appropriate to consider the different facets and risk factors of IRS in aggregate, rather than seeking 'independent' effects. Accordingly, treatment of insulin resistance per se has not yet been shown to reduce the incidence of cardiovascular complications. At the cellular level, excess insulin is involved in various elements of atherogenesis. It interacts with cytokines and growth factors in a cross talk among vascular wall cells and a variety of mediators that play a role in the establishment of atheroma. Excess insulin also plays an important role in concert with lipoproteins when they exhibit an abnormal pattern and become modified by oxidation and glycation. It is therefore currently hoped that the introduction of a new class of insulin sensitizing agents, the thiazolidinediones, may attenuate these processes. The thiazolidinediones act through ligand activation of a nuclear transcription factor, the peroxisomal proliferator-activated receptor-gamma (PPARgamma). Although this receptor was initially linked to lipid and glucose metabolism, recent data suggest that PPARgamma is also involved in the differentiation of mononuclear phagocytes, their inflammatory reactions, and macrophage conversion to foam cells. Thus, PPARgamma ligands may also be important regulators of monocyte/ macrophage gene expression during atherogenesis. PMID- 11220291 TI - The polycystic ovary syndrome: treatment with insulin sensitizing agents. PMID- 11220292 TI - Physiological and pharmacological regulation of insulin release: insights offered through exploitation of insulin-secreting cell lines. PMID- 11220293 TI - Sudden death in type 1 diabetes. PMID- 11220294 TI - Non-enzymatic glycation of lens proteins and haemoglobin-inhibition by pyruvate: an in-vivo study. AB - AIM: Previous studies have demonstrated that pyruvate can prevent protein glycation and oxidative stress under in-vitro conditions. The aim of this study was to examine the in-vivo effectiveness of this metabolite against glycation of lens crystallins and haemoglobin in galactosemic rats. METHODS: Sprague-Dawley rats were maintained on a 30% or 50% galactose-containing diet in the absence or presence of 2% or 5% pyruvate in food and water, respectively. The animals were killed subsequently and the extent of glycation of lens crystallins and haemoglobin was determined using an affinity column chromatograpic technique. RESULTS: Maintenance of rats on the high galactose diet resulted in a significant increase in glycation of both the proteins. The increase was faster and more substantial in the animals maintained on the 50% galactose diet than that in the animals fed a 30% galactose diet. The increase in the latter was also very significant. Supplementation with pyruvate inhibited the process. CONCLUSION: The inhibition is attributable to a competitive binding of pyruvate to the protein NH2 groups as well as to the antioxidant effect of the compound. The studies therefore suggest that this and other alpha-keto-acids may be physiologically useful in minimizing glycation and oxidative stress induced tissue pathology by the hyperglycaemic conditions, such as diabetes and galactosemia. The results are also considered pharmacologically significant. PMID- 11220296 TI - Glucose and fatty acid metabolism in type 2 diabetes mellitus: an assessment using low-dose insulin infusion and the hyperinsulinaemic euglycaemic clamp. AB - AIM: To assess whether resistance to the effects of insulin on lipid metabolism in type 2 diabetes mellitus parallels that demonstrated for glucose metabolism. METHODS: Thirteen patients with type 2 diabetes were studied (mean age 56.2 years, mean body mass index (b.m.i.) 28.7 kg m(-2)). The hyperinsulinaemic euglycaemic clamp (2 mU insulin kg(-1) min(-1)) and a low-dose insulin infusion technique were used in order to assess insulin effects on both glucose and lipid metabolism. RESULTS: Using the low-dose insulin infusion there were significant correlations between measures of insulin sensitivity for glucose metabolism and those for NEFA (r = 0.82, p < 0.01) and glycerol (r = 0.73, p < 0.01). Mean clamp glucose disposal was 33.4 micromol kgb.w.(-1) min(-1). There was no correlation between clamp glucose disposal and insulin sensitivity derived from the low-dose insulin infusion. CONCLUSIONS: At low insulin concentrations, insulin's effects on glucose metabolism (mainly suppression of hepatic glucose output) mirror those on inhibition of lipolysis. At the high insulin concentrations seen during the clamp, stimulation of glucose uptake provides a measure of maximal insulin action which does not parallel its physiological effects shown at lower concentrations. PMID- 11220295 TI - Rosiglitazone monotherapy improves glycaemic control in patients with type 2 diabetes: a twelve-week, randomized, placebo-controlled study. AB - AIM: Rosiglitazone is the most potent of the thiazolidinediones, a novel class of oral antidiabetic agents that reduce blood glucose levels by sensitizing peripheral tissues to insulin. This study was designed to identify doses of rosiglitazone that would lower fasting plasma glucose (FPG) in patients with type 2 diabetes. METHODS: In this 12-week, double-blind, multicentre study, 380 patients with FPG values > or =7.8 mmol/L (140 mg/dL) and < or =13.3 mmol/L (240 mg/dL) were randomly assigned to receive treatment with placebo or rosiglitazone, 0.05, 0.25, 1.0, or 2.0 mg twice daily. The primary efficacy parameter was changed in FPG from baseline after 12 weeks of treatment. Secondary endpoints were changes in HbA1c, fructosamine, C peptide, insulin, lipid levels, and body weight (b.w.). Safety monitoring included clinical laboratory evaluations, electrocardiography, and echocardiography. RESULTS: Rosiglitazone 1.0 and 2.0 mg b.i.d. produced significant decreases in FPG (p=0.0001). Fructosamine also decreased in patients treated with these two dosages (p=0.003 in the 2.0 mg b.i.d. group). Rosiglitazone 2.0 mg b.i.d. significantly reduced plasma insulin levels (p=0.0044) and free fatty acids (p=0.0014) compared with placebo. Total cholesterol (p=0.0001), HDL (p=0.0009), and LDL (p=0.0001) increased in the rosiglitazone 2.0 mg b.i.d. group, but there was no significant change in the total cholesterol/HDL ratio or triglyceride levels in any rosiglitazone treatment group. Clinically insignificant dose-dependent increases in b.w. were observed in the rosiglitazone 1.0 and 2.0 mg b.i.d. treatment groups. CONCLUSIONS: Twelve weeks of treatment with rosiglitazone 2.0 mg b.i.d. significantly decreases fasting plasma glucose, fructosamine, plasma insulin, and free fatty acids in patients with type 2 diabetes. Longer studies using higher doses will be needed to assess the efficacy and safety of rosiglitazone in patients with type 2 diabetes mellitus. PMID- 11220297 TI - Possible liver damage by biosynthetic human insulin. PMID- 11220298 TI - Anticipated US approval for rosiglitazone and pioglitazone. PMID- 11220299 TI - Bacterial sources and sinks of isoprene, a reactive atmospheric hydrocarbon. PMID- 11220300 TI - Preferential occurrence of diazotrophic endophytes, Azoarcus spp., in wild rice species and land races of Oryza sativa in comparison with modern races. AB - Several diazotrophic species of Azoarcus spp. occur as endophytes in the pioneer plant Kallar grass. The purpose of this study was to screen Asian wild rice and cultivated Oryza sativa varieties for natural association with these endophytes. Populations of culturable diazotrophs in surface-sterilized roots were characterized by 16S rDNA sequence analysis, and Azoarcus species were identified by genomic fingerprints. A. indigens and Azoarcus sp. group C were detected only rarely, whereas Azoarcus sp. group D occurred frequently in samples of flooded plants: in 75% of wild rice, 80% of land races of O. sativa from Nepal and 33% of modern cultivars from Nepal and Italy. The putatively endophytic populations of diazotrophs differed with the rice genotype. The diversity of cultured diazotrophs was significantly lower in wild rice species than in modern cultivars. In Oryza officinalis (from Nepal) and O. minuta (from the Philippines), Azoarcus sp. group D were the predominant diazotrophic putative endophytes in roots. In contrast, their number was significantly lower in modern cultivars of O. sativa, whereas numbers and diversity of other diazotrophs, such as Azospirillum spp., Klebsiella sp., Sphingomonas paucimobilis, Burkholderia sp. and Azorhizobium caulinodans, were increased. In land races of O. sativa, the diazotrophic diversity was equally high; however, Azoarcus sp. was found in high apparent numbers. Similar differences in populations were also observed in a culture-independent approach comparing a wild rice (O. officinalis) and a modern type O. sativa plant: in clone libraries of root-associated nitrogenase (nifH) gene fragments, the diazotrophic diversity was lower in the wild rice species. New lineages of nifH genes were detected, e.g. one deeply branching cluster within the anf (iron) nitrogenases. Our studies demonstrate that the natural host range of Azoarcus spp. extends to rice, wild rice species and old varieties being preferred over modern cultivars. PMID- 11220301 TI - Desulfotomaculum genus- and subgenus-specific 16S rRNA hybridization probes for environmental studies. AB - Based on comparative analysis of 16S rRNA sequences and the recently established phylogeny of the genus Desulfotomaculum, a set of phylogenetically nested hybridization probes was developed and characterized. A genus-specific probe targets all known Desulfotomaculum species (with the exception of Desulfotomaculum acetoxidans), and five specific probes target subclusters within the Desulfotomaculum genus. The dissociation temperature of each probe was determined experimentally. Probe specificities were verified through hybridizations with pure culture rRNA isolated from a wide variety of target and non-target organisms and through an evaluation of probe 'nesting' using samples obtained from four different environments. Fixation and hybridization conditions for fluorescence in situ hybridizations were also optimized. The probes were used in quantitative membrane hybridizations to determine the abundance of Desulfotomaculum species in thermophilic anaerobic digesters, in soil, in human faeces and in pig colon samples. Desulfotomaculum rRNA accounted for 0.3-2.1% of the total rRNA in the digesters, 2.6-6.6% in soil, 1.5-3.3% in human faeces and 2.5-6.2% in pig colon samples. PMID- 11220302 TI - 'Clay hutches': a novel interaction between bacteria and clay minerals. AB - Biofilm formation on a low-energy substratum floating on the surface of a water column overlying a polychlorinated biphenyl (PCB)-contaminated sandy clay soil was followed by light and electron microscopy. The biofilms that developed consisted of a dense lawn of clay aggregates, each one of which contained one or more bacteria, phyllosilicates and grains of iron oxide material, all held together by bacterial extracellular polysaccharides (EPS). The clay leaflets were arranged in the form of 'houses of cards' and gave the aggregates the appearance of 'hutches' housing the bacteria. Interestingly, although the soil is poor in carbon, and the weakly bioavailable PCBs constitute the principal source of carbon in this system, the bacteria contained electron-transparent structures presumed to be carbon storage granules. These, and the EPS material present in the hutches, indicate that carbon is not limiting in this system and, as PCBs have been found associated with the clay mineral fraction of the floating substratum, the clay particles may serve as carbon shuttles. The interesting possibilities that the 'clay hutches' may represent a 'soil microhabitat', a 'minimal nutritional sphere' and an 'effective survival unit' for autochthonous bacteria are noted. The formation of clay hutches by bacteria would seem to merit further investigation, particularly regarding their roles in bacterial processes in soil and in geological processes. PMID- 11220304 TI - Ecological study of a bioaugmentation failure. AB - A nitrifying sequencing batch reactor was inoculated twice with the aerobic denitrifying bacterium Microvirgula aerodenitrificans and fed with acetate. No improvement was obtained on nitrogen removal. The second more massive inoculation was even followed by a nitrification breakdown, while at the same time, nitrification remained stable in a second reactor operated under the same conditions without bioaugmentation. Fluorescent in situ hybridization with rRNA targeted probes revealed that the added bacteria almost disappeared from the reactor within 2 days, and that digestive vacuoles of protozoa gave strong hybridization signals with the M. aerodenitrificans-specific probe. An overgrowth of protozoa, coincident with the disappearance of free-living bacteria, was monitored by radioactive dot-blot hybridization only in the bioaugmented reactor. Population dynamics were analysed with a newly developed in situ quantification procedure of the probe-targeted bacteria. The nitrifying groups of bacteria decreased in a similar way in the bioaugmented and non-bioaugmented reactors. Other bacterial groups evolved differently. The involvement of different ecological parameters are discussed separately for each reactor. These results underline the importance of predator-prey interaction and illustrate the undesirable effects of massive bioaugmentation. PMID- 11220303 TI - Regulation of urease gene expression by Streptococcus salivarius growing in biofilms. AB - The metabolism of urea by urease enzymes of oral bacteria profoundly influences oral biofilm pH homeostasis and oral microbial ecology. The purpose of this study was to gain insight into the regulation of expression of the low pH-inducible urease genes in populations of Streptococcus salivarius growing in vitro in biofilms and to explore whether urease regulation or the levels of urease expression in biofilm cells differed significantly from planktonic cells. Two strains of S. salivarius harbouring urease promoter fusions to a chloramphenicol acetyltransferase (cat) gene were used: PurelCAT, containing a fusion to the full length, pH-sensitive promoter; or Pureldelta100CAT, a constitutively derepressed deletion derivative of the urease gene promoter. The strains were grown in a Rototorque biofilm reactor in a tryptone-yeast extract-sucrose medium with or without pH control. Both CAT and urease activities in biofilms were measured at 'quasi-steady state' and after a 25mM glucose pulse. The results showed that CAT expression in PurelCAT was repressed at relatively neutral pH values, and that expression could be induced by acidic pH after carbohydrate challenge. Biofilms of PurelCAT grown at low pH, without buffering, had about 20-fold higher CAT levels, and only a modest further induction could be elicited with carbohydrate pulsing. The levels of CAT in biofilms of PurelCAT grown in buffered medium were slightly higher than those reported for planktonic cells cultured at pH 7.0, and the levels of CAT in Purel-CAT growing at low pH or after induction were similar to those reported for fully induced planktonic cells. CAT activity in Pureldelta100CAT was constitutively high, regardless of growth conditions. Interestingly, urease activity detected in biofilms of the parent strain, S. salivarius 57.1, could be as much as 130-fold higher than that reported for fluid chemostat cultures grown under similar conditions. The higher level of urease activity in biofilms was probably caused by the accumulation of the stable urease enzyme within biofilm cells, low pH microenvironments and the growth phase of populations of cells in the biofilm. The ability of S. salivarius biofilm cells to upregulate urease expression in response to pH gradients and to accumulate greater quantities of urease enzyme when growing in biofilms may have a significant impact on oral biofilm pH homeostasis and microbial ecology in vivo. Additionally, S. salivarius carrying the pH-sensitive urease gene promoter fused to an appropriate reporter gene may be a useful biological probe for sensing biofilm pH in situ. PMID- 11220305 TI - Changes in community composition during dilution cultures of marine bacterioplankton as assessed by flow cytometric and molecular biological techniques. AB - Dilution cultures are a common technique for measuring the growth of bacterioplankton communities. In this study, the taxonomic composition of marine bacterioplankton dilution cultures was followed in water samples from Plymouth Sound and the English Channel (UK). Bacterial abundances as well as protein and DNA content were closely monitored by flow cytometry. Denaturing gradient gel electrophoresis (DGGE) of polymerase chain reaction (PCR)-amplified 16S rDNA fragments and fluorescence in situ hybridization (FISH) were applied directly to the water samples and to cells sorted from the dilution cultures based on their protein and DNA content. As expected, a rapid activation of bacteria occurred. However, molecular techniques showed that the community developed in the dilution culture within 1 day was significantly different from that in the original water samples. Whereas in the original samples, cells detectable by FISH were dominated by members of the Cytophagal Flavobacterium (CF) cluster, in dilution cultures, gamma-proteobacteria accounted for the majority of cells detected, followed by alpha-proteobacteria. An actively growing and an apparently non-growing population with average cellular protein contents of 24 and 4.5 fg respectively, were sorted by flow cytometry. FISH indicated mostly gamma- (64%) and alpha proteobacteria (33%) in the first active fraction and 78% members of the CF cluster in the second fraction. Sequencing of DGGE bands confirmed the FISH assignments of the latter two groups. The data presented clearly show that even relatively short-term dilution experiments do not measure in situ growth, but rather growth patterns of an enrichment. Furthermore, it was demonstrated that the combination of flow cytometric analysis and sorting combined with FISH and DGGE analysis presented a fairly rapid method of analysing the taxonomic composition of marine bacterioplankton. PMID- 11220306 TI - hexA of Erwinia carotovora ssp. carotovora strain Ecc71 negatively regulates production of RpoS and rsmB RNA, a global regulator of extracellular proteins, plant virulence and the quorum-sensing signal, N-(3-oxohexanoyl)-L-homoserine lactone. AB - The soft-rotting bacterium, Erwinia carotovora ssp. carotovora (E. c. carotovora), produces an array of extracellular enzymes (= exoenzymes), including pectate lyase (Pel), polygalacturonase (Peh), cellulase (Cel) and protease (Prt), as well as HarpinEcc, the elicitor of hypersensitive reaction (HR). The production of these exoenzymes and HarpinEcc responds to plant products and the quorum-sensing signal [N-(3-oxohexanoyl)-L-homoserine lactone; OHL] and is subject to both transcriptional and post-transcriptional regulation. hexA of E. c. carotovora strain Ecc71 (hereafter hexA71), like that of another E. c. carotovora strain, negatively controls the production of exoenzymes, OHL and virulence in E. c. carotovora strain Ecc71. In addition to exoenzymes, HexA71 negatively regulates the expression of hrpNEcc, the structural gene for HarpinEcc. Exoenzyme overproduction is abolished by OHL deficiency in a HexA- and Ohll- double mutant, indicating that HexA and OHL are components of a common regulatory pathway controlling exoenzyme production. HexA71 negatively affects RpoS, as the levels of this alternative sigma factor are higher in the HexA- mutant than in the HexA+ strain. However, a HexA- and RpoS double mutant produces higher levels of exoenzymes and transcripts of pel-1, peh-1 and celVgenes than the HexA- and RpoS+ parent. Thus, the elevated levels of RpoS protein in the HexA mutant do not account for exoenzyme overproduction. The following evidence associates for the first time the phenotypic changes in the HexA mutant to overproduction of rsmB RNA, a global regulator of exoenzymes, HarpinEcc, OHL and secondary metabolites. Analyses of rsmB transcripts and expression of an rsmB lacZoperon fusion in E. c. carotovora strain Ecc71 revealed that HexA71 negatively regulates transcription of rsmB. Multiple copies of hexA71+ DNA suppress various phenotypes, including exoenzyme production in E. c. carotovora strain Ecc71, and concomitantly inhibit the production of rsmB, pel-1, peh-1, celV and hrpNEcc transcripts. Multiple copies of rsmB+ DNA, on the other hand, stimulate exoenzyme production by relieving the negative effects of a chromosomal copy of hexA+. The occurrence of hexA homologues and the negative effect of the dosage of hexA71 DNA on rsmB transcripts were also detected in other E. c. carotovora strains as well as Erwinia carotovora atroseptica and Erwinia carotovora betavasculorum. Extrapolating from the findings with LrhA, the Escherichia coli homologue of HexA, and the presence of sprE homologues in E. carotovora subspecies, we propose that HexA71 controls several regulatory pathways in E. carotovora including rsmB transcription and the production of SprEEcc which, in turn, affects RpoS levels. A model is presented that integrates the findings presented here and our current knowledge of the major regulatory network that controls exoprotein production in soft-rotting Erwinia carotovora subspecies. PMID- 11220307 TI - Matching molecular diversity and ecophysiology of benthic cyanobacteria and diatoms in communities along a salinity gradient. AB - The phylogenetic diversity of oxygenic phototrophic microorganisms in hypersaline microbial mats and their distribution along a salinity gradient were investigated and compared with the halotolerances of closely related cultivated strains. Segments of 16S rRNA genes from cyanobacteria and diatom plastids were retrieved from mat samples by DNA extraction and polymerase chain reaction (PCR), and subsequently analysed by denaturing gradient gel electrophoresis (DGGE). Sequence analyses of DNA from individual DGGE bands suggested that the majority of these organisms was related to cultivated strains at levels that had previously been demonstrated to correlate with characteristic salinity responses. Proportional abundances of amplified 16S rRNA gene segments from phylogenetic groupings of cyanobacteria and diatoms were estimated by image analysis of DGGE gels and were generally found to correspond to abundances of the respective morphotypes determined by microscopic analyses. The results indicated that diatoms accounted for low proportions of cells throughout, that the cyanobacterium Microcoleus chthonoplastes and close relatives dominated the communities up to a salinity of 11% and that, at a salinity of 14%, the most abundant cyanobacteria were related to highly halotolerant cultivated cyanobacteria, such as the recently established phylogenetic clusters of Euhalothece and Halospirulina. Although these organisms in cultures had previously demonstrated their ability to grow with close to optimal rates over a wide range of salinities, their occurrence in the field was restricted to the highest salinities investigated. PMID- 11220308 TI - Diversity and community structure within anoxic sediment from marine salinity meromictic lakes and a coastal meromictic marine basin, Vestfold Hilds, Eastern Antarctica. AB - 16S rDNA clone library analysis was used to examine the biodiversity and community structure within anoxic sediments of several marine-type salinity meromictic lakes and a coastal marine basin located in the Vestfolds Hills area of Eastern Antarctica. From 69 to 130 (555 total) 16S rDNA clones were analysed from each sediment sample, and restriction fragment length polymorphism (RFLP) and sequence analysis grouped the clones into 202 distinct phylotypes (a clone group with sequence similarity of >0.98). A number of phylotypes and phylotype groups predominated in all libraries, with a group of 10 phylotypes (31% of clones) forming a novel deep branch within the low G+C Gram-positive division. Other abundant phylotypes detected in several different clone libraries grouped with Prochlorococcus cyanobacteria, diatom chloroplasts, delta proteobacteria (Desulfosarcina group, Syntrophus and Geobacterl Pelobacter/Desulphuromonas group), order Chlamydiales (Parachlamydiaceae) and Spirochaetales (wall-less Antarctic spirochaetes). Most archaeal clones detected (3.1% of clones) belonged to a highly diverged group of Euryarchaeota clustering with clones previously detected in rice soil, aquifer sediments and hydrothermal vent material. Little similarity existed between the phylotypes detected in this study and other clone libraries based on marine sediment, suggesting that an enormous prokaryotic diversity occurs within marine and marine-derived sediments. PMID- 11220309 TI - Microbes and metals. PMID- 11220310 TI - TRAP--transformation and its connection to pathogenicity and antibiotic resistance. PMID- 11220311 TI - A new sample preparation technique for organochlorines in cod liver oil combining SPE and NP-HPLC with HRGC-ECD. AB - The analysis of semivolatile organochlorines (polychlorinated biphenyls and chlorinated pesticides) in less polluted biomaterials requires specific strategies in controlling the blank in sample preparation. The procedure described here allows to decrease significantly the level of contamination during the clean-up step of fish oil. Solid-phase-extraction (SPE) on LiChrolut EN and normal phase HPLC in the normal- and the backflush-mode were used to reduce the amount of solvents needed and the analysis time compared to established clean-up procedures. With a certified reference material (BCR-CRM 349; Cod Liver Oil) the precision and effectiveness of the new method were validated. Recovery rates of the Internal Standards (PCB 103 and TCN) lay between 75% and 90% at the microg/kg lipid level. The quantitative analyses were carried out by high resolution gas chromatography with electron capture detector (HRGC-ECD). PMID- 11220312 TI - Surface characterization of commercial fibers for solid-phase microextraction and related problems in their application. AB - The surfaces of commercially available polydimethylsiloxane (PDMS) and Carboxen PDMS fibers for solid-phase microextraction (SPME) were investigated by optical and electron microscopy. Damage to the coating as well as contamination of new fibers and a highly variable number of pores in Carboxen-PDMS coatings were observed. Together with the contamination of the fibers during their use with metallic particles originating from the SPME fiber holder they are possible explanations for the problems encountered in the analysis of organolead, organotin and organosulfur compounds, such as artifact formation and low repeatability. PMID- 11220313 TI - Automized procedures for the determination of ozone and ammonia contents in air by using the chromatomembrane method for gas-liquid extraction. AB - Chromatomembrane cells (CMC) operate as unique manifolds for extraction and preconcentration procedures in computer controlled flow-injection-analysis (FIA). By coupling to an ion chromatograph and to a conductometer, respectively, instrumentation is obtained that allows the pretreatment and the detection of ozone- and ammonia-containing samples after absorption of the gaseous constituents of air inside a chromatomembrane cell. The analysis of air even in the presence of liquid aerosols is discussed. PMID- 11220314 TI - Transport processes through track-etch membrane filters in a reagent delivery cell. AB - A reagent delivery cell with a track-etch membrane filter for on-line dilution of concentrated salt solutions is described. The influence of several system parameters such as concentration of the stock solution, temperature. transmembrane pressure and the dependence on the diffusion coefficients of several salt components on the dilution was evaluated. As an application example, the use of the reagent delivery cell for on-line calibration of an atomic absorption spectrometer was studied. Fluxes through the membrane filter of 10 to 50 nL mm(-2) min(-1) with relative standard deviations of 0.8% within a day and 1.9% from day to day were achieved. The permeation experiments with the track etch membrane filter for the dilution of aqueous solutions of several chlorides and sodium salts confirm a diffusion process. Flux rates can be estimated mathematically using Fick's first law with an agreement between measured and calculated dilution factors within 86 to 113%. PMID- 11220315 TI - Spacer-modified stationary phases for anion chromatography: alkyl- and carbonylalkylspacers--a comparison. AB - A comparison of two separation columns for high-capacity anion chromatography is presented. The distinctive feature of both packing materials is the structure of the alkyl-chain (spacer-group) between the polymer-backbone and the functional group. All other parameters, e.g. exchange capacity, functionality and length of the spacer-arm, are identical. The retention behavior of the so-called standard anions is investigated on both columns under identical chromatographic conditions using an experimental design technique in the course of which the composition of the elution system applied is varied. The statistical treatment of the retention data offers the possibility to explain the different chromatographic behavior of both stationary phases, at least qualitatively. PMID- 11220316 TI - New stationary phase based on beta-cyclodextrin for normal-phase HPLC group separation of organic nitrates. AB - The synthesis of a beta-cyclodextrin-silica normal-phase (NP)-liquid chromatography (LC) stationary phase is reported. Silica gel was modified with (3 bromopropyl)trimethoxysilane to a 3-bromopropyl-silica that was reacted with beta cyclodextrin, resulting in a beta-cyclodextrin-silica. To prove its usefulness in group-separation of organic nitrates among others, a mixture of three groups of organic nitrates was separated. The results are compared with those obtained on a nitrated polyol-silica that has recently been reported. The alkyl dinitrates exhibt higher retention relatively to alkyl mononitrates on the new phase. This allows to cut the LC fractions in a way that the alkyl mononitrates and phenylalkyl nitrates appear in one fraction and the dinitrates in a second one without any overlap of the two fractions. PMID- 11220317 TI - Influence of column geometry on the ion chromatographic separation of aluminium species. AB - The dependence of the degree of disintegration and therefore the applicability of ion chromatography for the speciation of aluminium fluoride species was examined for two different column geometries, a standard bore and a microbore column. Besides mathematical calculations, the temperature of the separation column was varied between -5 and 50 degrees C for the observation of a temperature-dependent decomposition of the species. All species were detected by UV photometry after post-column reaction with Tiron. The results showed that the disintegration of the higher coordinated Al fluoride species (AlFn with n >2) could be dramatically reduced utilizing the microbore technique. In contrast to the standard bore technique the column temperature is of minor importance. The agreement between speciation data experimentally determined by microbore chromatography and those calculated using stability constants is quite good. The standard bore technique showed bigger differences between calculated and experimentally determined species distributions. PMID- 11220318 TI - Comparison of sodium tetraethylborate and sodium tetra(n-propyl)borate as derivatization reagent for the speciation of organotin and organolead compounds in water samples. AB - The influence of pH on the propylation with sodium tetra(n-propyl)borate of butyl and phenyltins as well as for trimethyl- and triethyllead was investigated. Ethylation and propylation with tetraalkylborates were compared with regard to derivatization yields and figures of merit for organotin compounds in real water samples. Similar results for limit of detection (3-12 ng/L as tin), derivatization yield (40-100%) and relative standard deviation of the method (3 10%) were achieved for derivatization with the two tetraalkylborates. Propylation is thus the preferred method for the simultaneous determination of environmentally relevant organotin and organolead compounds. The handling of the hygroscopic and air sensitive reagents NaBEt4 and NaBPr4 was simplified by dissolving them in tetrahydrofurane. The reagent solutions in tetrahydrofurane can be stored for at least one month at 4 degrees C in the dark without observing any decrease in the derivatization efficiency. PMID- 11220319 TI - Spectrophotometric and direct-reading methods for the analysis of gas phase peroxyacetic acid. AB - A new method for the determination of peroxyacetic acid (PAA) in gas phase samples is described. It is based on the oxidation of ABTS (2,2'-azino-bis(3 ethylbenzothiazoline)-6-sulfonate) by PAA with formation of a radical cation which is characterized by four strong absorption maxima between 405 nm and 810 nm. These allow for sensitive spectrophotometric determination of the peracid. The selectivity of the method towards hydrogen peroxide is strongly dependent on the sampling method used. Impinger sampling and sampling based on the use of coated solid sorbents (test tubes) was performed. Limits of detection are 10(-8) mol, limits of quantification are 5 x 10(-8) mol, the linear range consists of 1.5 concentration decades in both cases. Using ABTS-coated test tubes above 1 x 10(-7) mol, direct reading of the results is possible and may be used as rapid screening method for the PAA concentration. PMID- 11220320 TI - Analysis of halogenated C1/C2-trace compounds in marine atmosphere. AB - Patterns of volatile ECD-active substances in marine air at the ultra trace level were investigated. The protocol used carbon based adsorbents, thermodesorption and thick film HRGC-ECD together with a second ECD in line with oxygen doped make up gas. The latter ECD mode leads to an increased sensitivity for chloromethane. dichloromethane, and other important chlorinated substances with an otherwise low response at an ECD driven with oxygen-free nitrogen or argon/methane. The experimental set-up is easily to employ. Air samples were taken on two cruises of the German research vessel R/V "Polarstem" in the Atlantic Ocean to determine the background pattern of all volatile halocarbons from CF3Cl to CHI3 in marine air. PMID- 11220321 TI - Direct observation of the formation of aromatic pollutants in waste incineration flue gases by on-line REMPI-TOFMS laser mass spectrometry. AB - On-line REMPI-TOFMS laser mass spectrometry (Resonance Enhanced Multi-Photon Ionization-Time-Of-Flight Mass Spectrometry) was used to monitor combustion and pyrolysis byproducts from industrial combustion processes, including polycyclic aromatic hydrocarbons (PAH) and monochlorobenzene in the flue gas of an industrial 22 MW hazardous waste incineration plant. Sampling at different places in the flue gas stream revealed the complexity of the processes responsible for the formation of the different chemical species, while time resolved measurements depicted the emission dynamics. PMID- 11220322 TI - Analysis of the cancerogenic heterocyclic aromatic amines in fried meat. AB - Heterocyclic aromatic amines (HAs) are potential cancerogens found in heated meat and fish. From the precursors creatin/ine amino acids and carbohydrates the HAs are formed in very complex reactions at high temperatures. The concentration in meat is very low and the analysis especially the clean-up is critical due to the complex meat matrix. The concentrations in heated meat are in the low ng/g range. With increasing time of heating and the temperature the concentration of the HAs (MeIQx, IQ, 4,8-DiMeIQx, PhIP) can increase from 0 to 5 ng/g at 140 degrees C for 15 min to 20 to 40 ng/g at 220 degrees C for 35 min. MeIQ is formed at a significant lower amount. PMID- 11220323 TI - Analysis of anthocyane glycosides in human serum. AB - Anthocyanins, natural food antioxidants, can be identified in human blood plasma using a restricted access phase for removal of the proteins and enrichment of the anthocyanins. In preliminary studies the spray dried elderberry juice was shown to have antioxidant activities in vitro. From the four known anthocyanins present in elderberry (Sambucus nigra) the two main components could be analysed quantitatively enabling their analysis in blood. Using a restricted access phase and a column switching set-up the injection of high volumes of concentrated protein solutions is possible. Additional, by using high injection volumes the sensitivity is increased due to a concentration of the analytes on the restricted access phase. The limit of quantification reached was 0.5 ng/mL. In this experiment the maximum concentration in blood (35 mg/mL) was observed after 1 h with a quick decay. PMID- 11220324 TI - Quantification of beta-trace protein and detection of transferrin isoforms in mixtures of cerebrospinal fluid and blood serum as models of rhinorrhea and otorrhea diagnosis. AB - Different mixtures from a serum pool and a cerebrospinal fluid (CSF) pool were used as models to study CSF contamination in secretions by determining two CSF specific proteins: beta-trace protein (beta-TP) and the asialo-transferrin (a-Tf) band which was detected by isoelectric focusing (IEF) with Tf specific immunofixation. Beta-TP and total Tf were measured immunonephelometrically. Secretion/serum ratios of beta-TP content > 2.0 indicated CSF contaminations with > or = 5% (v/v) CSF; this was confirmed by detecting the a-Tf band by IEF. Reliable a-Tf bands were only revealed with secretion/serum rations of Tf contents < 0.1, indicating an interference of major sialo-Tf fractions with the a TF band detection in the sample. For CSF detection in rhinorrhea and otorrhea, complementary use of beta-TP assay and a-Tf assay is recommended. Preanalytically, dilution or concentration of the sample as well as denaturation of Tf and beta-TP should be prevented by optimizing sample collection. PMID- 11220326 TI - Determination of endogenous and exogenous estrogens in effluents from sewage treatment plants at the ng/L-level. AB - An analytical method for the determination of the major endogenous and exogenous estrogenic steriods in effluent water samples of sewage treatment plants (STPs) with a LOQ down to 1 ng/L and below has been developed. The exogenous estrogen 17alpha-ethynylestradiol, frequently used as estrogenic component in oral contraceptives, and the endogenous estrogen 17beta-estradiol show the highest estrogenic potential, therefore they were part of our target compounds. In addition, the content of the synthetic gestagen levonorgestrel, also often administered in oral contraceptives, was determined. A solid-phase extraction system for high volume sampling of water up to 25 L was implemented. Two types of adsorbent, Amberlite XAD 2 and a mixture of LiChrolut EN/Bondesil C-18, respectively, were tested for their extraction efficiency of these polar analytes. Recovery rates with LiChrolut EN/Bondesil C-18 ranged up to 94%, whereas sampling on XAD 2 led only to poor recoveries below 40%. After a liquid chromatographic clean-up step on silicagel the steroids were converted into their trimethylsilyl-ethers by the reaction with MSTFA/TMSI (N-methyl-N-trimethylsilyl 2,2,2-trifluoroacetamide, trimethylsilyliodide) and were then determined by HRGC/MS in the selected ion mode. A limit of quantification over the whole procedure of at least 1 ng/L was reached for all analytes. In several effluent samples the input of estrogens by the STP of the cities Ulm and New Ulm into the river Danube was characterised. The concentrations commonly found ranged from 1 ng/L up to 13 ng/L, depending on the respective steroid. PMID- 11220325 TI - Comparison of ion chromatographic methods based on conductivity detection, post column-reaction and on-line-coupling IC-ICP-MS for the determination of bromate. AB - An established method for the determination of the disinfection by-product bromate is ion chromatography (IC). This paper presents a comparison of three IC methods based on either conductivity detection (IC-CD), a post-column-reaction (IC-PCR-VIS) or the on-line-coupling with inductively coupled plasma mass spectrometry (IC-ICP-MS). Main characteristics of the methods such as method detection limits (MDL), time of analysis and sample pretreatment are compared and applicability for routine analysis is critically discussed. The most sensitive and rugged method is IC-ICP-MS, followed by IC-PCR-VIS. The photometric detection is subject to a minor interference in real world samples, presumably caused by carbonate. The lowest sensitivity is shown by the IC-CD method as slowest method compared, which, in addition, requires a sample pretreatment. The highest amount of information is delivered by IC-PCR-VIS, which allows the simultaneous determination of the seven standard anions and bromate. PMID- 11220327 TI - Determination of acetaldehyde in tobacco smoke using N-methyl-4-hydrazino-7 nitrobenzofurazan and liquid chromatography/mass spectrometry. AB - A liquid chromatography/mass spectrometry (LC/MS) method for the determination of carbonyl compounds based on derivatization with N-methyl-4-hydrazino-7 nitrobenzofurazan (MNBDH) has been developed. Atmospheric pressure chemical ionization (APCI) in the positive mode proved the most versatile ionization technique for MNBD-hydrazones. APCI/MS spectra were recorded and the detection limits were determined for [M+H]+, 13C2 acetaldehyde MNBD-hydrazone has been synthesized and characterized. It is applied as internal standard for the quantification of acetaldehyde. Tobacco smoke has been investigated concerning its carbonyl content. Acetaldehyde was identified as main product and quantified by LC/MS using internal standardization. The result is in good agreement to quantification data obtained with UV/vis detection. PMID- 11220328 TI - Investigating the potential of high-performance liquid chromatography with atmospheric pressure chemical ionization-mass spectrometry as an alternative method for the speciation analysis of organotin compounds. AB - Liquid chromatography with atmospheric pressure chemical ionization-mass spectrometry (LC-APCI-MS) was applied for the determination of butyl- and phenyltin compounds. Chromatography was performed on a 30 x 2 mm, 3 microm C18 column, enabling the separation of mono-, di- and trisubstituted butyl- and phenyltin compounds in less than 10 min using a water/1% trifluoroacetic acid/methanol gradient. While satisfactory retention and resolution is achieved for the di- and trisubstituted butyl- and phenyltin compounds, monobutyltin and monophenyltin cannot be resolved chromatographically. Depending on the parameter values of the interface, APCI-MS detection allows both specific detection of the molecular ion or cluster ion at low to intermediate fragmentor voltages or quasi element specific detection of the Sn+ ion released from the organotin compounds at high fragmentor voltages. The sensitivity of MS detection is similar for butyl and phenyltin compounds, but varies largely from mono- to trisubstituted organotin compounds with tributyl- and triphenyltin being the most sensitively detectable compounds. Detection limits are in the 20-65 pg (abs.) range in SIM mode and in the 750-2000 pg (abs.) range in the scan mode for tributyl- and triphenyltin and for dibutyl- and diphenyltin, respectively. Monobutyl- and monophenyltin can be detected with much lower sensitivity which, together with their unfavorable chromatographic behavior, accounts for the fact that they cannot be analyzed at environmentally relevant concentrations. Although LC-APCI MS is generally less sensitive than comparable GC methods, it is applicable to the analysis of environmental samples as demonstrated by the analysis of the PACS 2 sediment certified reference material. Although the derivatization of the ionic organotin compounds, which particularly in real samples is a potential source of error, is circumvented when LC-APCI-MS is used, the extraction step is still critical and may lead to underestimation when quantitation is not done by the method of standard addition. PMID- 11220329 TI - On-line and in-situ detection of polycyclic aromatic hydrocarbons (PAH) on aerosols via thermodesorption and laser-induced fluorescence spectroscopy. AB - A fiber optical sensor system for the determination of polycyclic aromatic hydrocarbons (PAH) on aerosols by laser-induced, time-resolved fluorescence is combined with a thermodesorption device. The sensor system is based on an aerosol flow cell, which is fibre-optically coupled to a pulsed nitrogen laser for excitation and the detection system. Time-resolved fluorescence emission spectra are detected by a monochromator equipped with a photomultiplier and a fast digital storage oscilloscope. The analytical figures of merit of the thermodenuder are reported for benzo[a]pyrene, benzo[b]fluoranthene, and benzo[ghi]-perylene on ultrafine soot and NaCl aerosols. By thermodesorption of the PAH, problems due to quenching of the PAH fluorescence by the bulk aerosol material or excimer formation on the aerosol surface were avoided. For the PAH under study, the sensitivity was improved considerably and detection limits between 110 and 850 ng m(-3) were attained, while a response time of 2-3 min was achieved with the thermodenuder. A calibration for PAH on ultrafine soot and NaCl aerosols was established independent of the aerosol substrate. PMID- 11220330 TI - Mercury as a Global Pollutant--the fifth international conference. PMID- 11220331 TI - Assessing the contribution of natural sources to the global mercury cycle: the importance of intercomparing dynamic flux measurements. AB - In order to constrain the contribution of natural sources of mercury to the global atmospheric cycle we need to: 1. assess the methods used to measure mercury flux, 2. characterize those factors most important in controlling emissions, 3. develop a database of emissions from representative locations, and 4. develop a means of scaling up measured emissions to estimate fluxes on a regional basis. This paper describes how an international multi-collaborator project, the Nevada SToRMS Project, held September 1997 in Reno, Nevada, USA, contributed to our ability to constrain natural source mercury emissions. This study entailed a field intercomparison of those methods typically applied to measure mercury flux from substrate combined with evening workshops and round table discussions. The project was unique in that it focused on assessing our ability to measure the flux of an environmental contaminant. This is more difficult than measurement of the concentration of a contaminant because of the number and nature of the variables which influence the field flux measurements, including experimental design, spatial heterogeneity, and temporally changing environmental conditions. As a result of the Nevada SToRMS Project, rapid and significant advances in our understanding of how to constrain emission fluxes from large areas of mercury enrichment were realized. Because this intercomparison was a multi-investigator project, the results and implications of the project have been broadly circulated. The sincere scientific collaboration that evolved amongst those working on the study has led to significant advancements in our understanding of the fate and transport of mercury in the environment. PMID- 11220332 TI - Improved determination of gaseous divalent mercury in ambient air using KCl coated denuders. AB - An improved method for the determination of gaseous divalent mercury (GDM) in ambient air using KCl coated denuders has been developed and tested. GDM collected in the KCl coated denuders can be quantitatively desorbed at 450 degrees C in 10 min. After being complete thermally reduced to Hg0 at 900 degrees C, all mercury released from the denuder is pre-concentrated on the analytical Au trap, and detected by cold vapor atomic fluorescence spectrometry (CVAFS). The absolute detection limit of the method is less than 3 pg. Preliminary data of GDM concentration in ambient air from different sampling stations show that GDM concentrations in the urban air of Goteborg are much higher than in rural air (Rorvik and Sasetta), which indicates the anthropogenic origin of GDM. PMID- 11220333 TI - Mercury measurements in ambient air near natural gas processing facilities. AB - Natural gas from gas fields around the globe often contains mercury, along with a large number of other harmful substances (CO2, H2S, RSH, COS, etc). Mercury's potentially harmful effect on humans and on the ecological system as a whole as well as the technological risk regarding very sophisticated and expensive process equipment and catalysts make its removal imperative. There is a need for the highest efficiency for mercury removal and for permanent improvement and enhancement of technological and control procedures, including analytical instruments and measurements. Mercury concentration measurements in the ambient air performed during natural gas processing confirm that the design of the system at the Molve gas plant is adequate to meet the mercury removal objectives. The obtained results also illustrate in an excellent way the use of the portable instrument to identify and prevent potential mercury generated hazards linked to specific industrial processes. PMID- 11220335 TI - Analysis and stability of mercury speciation in petroleum hydrocarbons. AB - Raw petroleum and natural gas often contain high concentrations of mercury, which can be damaging to the metal components of production facilities, as well as to the environment. Various Hg species have different properties in terms of mobility, reactivity and bioavailability. Thus, for cost-effective decisions regarding plant design, Hg extraction, and pollution control, speciation information must be available at the production facility. In this paper, a simple, wet chemical speciation method, which provides data on Hg(o), dissolved and particulate total Hg, Hg(II), and methyl Hg is presented. The method incorporates species-specific extraction and separation procedures, followed by cold vapor atomic fluorescence spectrometry (CVAFS). For each species, detection limits of approximately 0.1 ng/g were obtained. Storage experiments in various containers showed that organo-mercury species were stable for at least 30 days in all containers except those made of polyethylene; and Hg(o) was stable in all containers except those made of stainless steel or polyethylene. Hg(II) was rapidly lost from all containers except those made of aluminum, which rapidly converted it to Hg(o), which was stable. In general, most of the total Hg in petroleum products was particulate Hg, followed by dissolved Hg(II) and Hg(o). Sub-ng/g concentrations of methyl-Hg were observed in most samples. PMID- 11220334 TI - Clean conditions for the determination of ultra-low levels of mercury in ice and snow samples. AB - Laboratory facilities and methods are presented for the determination of ultra low levels of mercury (Hg) in ice and snow samples originating from polar ice caps or temperate regions. Special emphasis will be given to the presentation of the clean laboratory and the cleaning procedures. The laboratory is pressurized with air filtered through high efficiency particle filters. This first filtration is not enough to get rid of contamination by Hg in air. Experiments are conducted in a clean bench, especially built for Hg analysis, equipped with both particle filter and activated charcoal filter. It allows to obtain very low levels of atmospheric Hg contamination. Ultrapure water is produced for cleaning all the plastic containers that will be used for ice and snow samples and also for the dilution of the standards. Hg content in laboratory water is about 0.08+/-0.02 pg/g. A Teflon system has been developed for the determination of Hg in ice and snow samples based on Hg(II) reduction to Hg(0) with a SnCl2/HNO3 solution followed by the measurement of gaseous Hg(0) with a Hg analyzer GARDIS 1A+ based on the Cold Vapor Atomic Absorption Spectroscopy method. Blank determination is discussed. PMID- 11220336 TI - Gold electrodes from recordable CDs for mercury quantification by flow injection analysis. AB - The development of a new methodology for the construction of very efficient flow cells for mercury detection by potentiometric stripping analysis, employing the thin gold layer of recordable CDs as working electrode is reported. This new source of electrodes (CDtrodes) show very attractive performance, similar to that obtained with commercial gold electrodes, with superior versatility. The low cost of this new source of "gold electrodes" allows a frequent replacement of the electrode, avoiding cumbersome clean-up treatments. Various experimental parameters have been optimized to yield low detection limits (0.25 ng/mL of mercury for 5 min deposition at 0.3 V) and good precision (standard deviation of 1.9% was obtained for 15 repetitive measurements using 10 ng/mL of mercury). Standard curves were found to be linear over the range of 0.5-100 microg L(-1) of mercury. The flow cells developed were used for the quantification of mercury in oceanic and tap water. PMID- 11220337 TI - Analytical validity of the determination of mercury in whole blood and urine- results of the German external assurance programme for toxicological analysis in biological materials. AB - The determination of mercury concentrations in blood and urine is currently the best way of monitoring individual uptake of organic and inorganic mercury. In Germany these determinations must be carried out under the conditions of an external quality assurance programme. The German performance evaluation, based on reference values established by reference laboratories yields success rates in percent for the participants in the intercomparison programme of about 60%. A Canadian evaluation system based on two evaluations scores, yields success rates of 25-50% for "good performance" and of 65-80% for "acceptable performance". The determination of mercury in blood and urine is at present not carried out with the necessary reliability. PMID- 11220338 TI - A methodological study of mercury speciation using dogfish liver CRM (DOLT-2). AB - The purpose of the study was to optimise analytical methods for determination of the chemical speciation of mercury in studies of protective mechanisms of selenium. Optimisation of the methods was performed using CRM DOLT-2 (Dogfish liver), both in its original form and after separation of various fractions. The sample was homogenised with 10 mM Tris-HCl buffer (pH 7.6) and ultracentrifuged. The soluble phase obtained was applied to a size exclusion chromatography column (Sephadex G-75 column) for separation of various protein fractions. Total mercury (total Hg), monomethyl mercury (MeHg) and selenium (Se) were determined in whole dogfish liver tissue and its soluble and insoluble phases (pellet). Different approaches for determination of total Hg and MeHg were compared. Simultaneous determination of MeHg and inorganic mercury (Hg2+) was based on alkaline dissolution and/or acid leaching, followed by ethylation, room temperature precollection, isothermal gas chromatography (GC), pyrolysis and detection with cold vapour atomic fluorescence spectrometry (CVAFS). The sum of MeHg and Hg2+ was compared to total Hg results obtained by acid digestion and CVAAS detection. The accuracy of MeHg determination was checked by its determination using acid leaching at room temperature, solvent extraction, back extraction into Milli-Q water, ethylation, GC and CVAFS detection. For the insoluble phase it is recommended to use solvent extraction for MeHg and acid digestion CVAAS for total Hg. For determination of MeHg and Hg2+ in the lyophilised sample and water soluble fractions containing low concentrations of mercury species, the simultaneous measurement of MeHg and Hg2+ after alkaline dissolution is the most appropriate method. PMID- 11220339 TI - A low-cost non instrumental method for semiquantitative determination of mercury in fish. AB - A non instrumental method for the semiquantitative determination of mercury in fish is described. The sample is acid digested and the mercury vapor released after chemical reduction with SnCl2. The mercury vapor is then collected on a detecting paper covered with an emulsion of Cu2I2, 3% carboxymethylcellulose and MgCl2 as moistener agent. The colored Cu2[HgI4] complex is formed and the color intensity is proportional to the mercury concentration in the original sample. Parameters such as sample mass/digestion solution volume ratio, emulsion composition, paper covering technique, carrier gas flow were investigated. Comparative studies using CVAAS and digital color analysis after scanning the papers confirmed the applicability of the method to real samples. PMID- 11220340 TI - Determination of methylmercury in fish tissue by gas chromatography with microwave-induced plasma atomic emission spectrometry after derivatization with sodium tetraphenylborate. AB - The detection of methylmercury species (MeHg) in fish tissue was investigated. Samples were digested with KOH-methanol and acidified prior to extraction with methylene chloride. MeHg was back-extracted from the organic phase into water. An aliquot of this aqueous solution (buffered to pH 5) was subjected to derivatization with sodium tetraphenylborate (NaBPh4) and then extracted with toluene. The organic phase containing MePhHg was injected into a gas chromatograph (GC) which is on-line with a microwave-induced plasma atomic emission spectrometer (MIP-AED). The quantification limit was about 0.6 microg/g and 0.1 microg/g of MeHg (as Hg) for 0.08 g of freeze-dried fish powder and 0.5 g of fresh samples, respectively. Two certified reference materials, CRM 464 (tuna fish) from Community Bureau of Reference-BCR and DORM-2 (dogfish muscle) from National Research Council Canada-NRC were selected for checking the accuracy of the method. This methodology was applied to the determination of MeHg in some kinds of fish from the Carmo river with alluvial gold recovery activities ("garimpos") in Mariana, Minas Gerais, Brazil. PMID- 11220341 TI - Discovery of a transalkylation mechanism--identification of ethylmercury+ at a tetraethyllead-contaminated site using sodiumtetrapropylborate, GC-AED and HPLC AFS. AB - Although organolead as a gasoline additive is banned in most countries, contamination by organolead compounds is still present. Little is known about transformation reactions of organolead compounds and especially transalkylation reactions with other metals. Laboratory experiments to clarify transalkylation reactions between organolead and inorganic mercury, and investigations of sites, where organolead compounds were emitted, are reported. Under laboratory conditions, inorganic mercury is ethylated to ethylmercury+ in presence of tetraethyllead. These transalkylations take place very fast and almost completely. In soil samples from an industrial site contaminated with organolead compounds and inorganic mercury, EtHg+ was clearly identified in high concentrations (up to 46 mg Hg/kg dw). Furthermore, methylmercury+ was found in concentrations up to 27 mg Hg/kg dw. It is the first time, that a transethylation of an organolead compound to an organomercurial compound in the environment is reported. It must be assumed, that this transalkylation takes place at sites, where organolead compounds occur and Hg2+ is available. Thus, it will be necessary to assess the risk of these sites. PMID- 11220342 TI - Optimization of HPLC-ICP-AES for the determination of arsenic species. AB - High performance liquid chromatography coupled to ICP-AES detection provides a rapid, reliable and sensitive method for arsenic speciation. The separation of As(III), As(V), DMA and MMA was achieved with ion exchange chromatography coupled to an axially-viewed sequential ICP-AES. After optimization of the chromatographic parameters (pH and concentration of the mobile phase), a careful study of the interface was conducted. Five nebulizers associated to three spray chambers were tested. Response of the ICP to each arsenic species was strongly affected by the selection of the nebulizer and spray chamber, however similar responses were obtained for each arsenic species. Best signal-to-noise ratios were obtained by using a microconcentric nebulizer and a cyclone spray chamber and did not affect the chromatographic resolution. Detection limits better than 10 microg L(-1) were obtained for As(III), DMA, MMA and 20 microg L(-1) for As(V), which is a significant improvement over previously published results. PMID- 11220343 TI - Fiber-optic microsensor for high resolution pCO2 sensing in marine environment. AB - A fast responding fiber-optic microsensor for sensing pCO2 in marine sediments with high spatial resolution is presented. The tip diameter varies typically between 20 and 50 microm. In order to make the pH-indicator 8-hydroxypyrene-1,3,6 trisulfonate soluble in the ethyl cellulose matrix, it was lipophilized with tetraoctylammonium as the counterion [HPTS-(TOA)4]. The microsensor was tuned to sense very low levels of dissolved carbon dioxide which are typically present in marine systems. The detection limit is 0.04 hPa pCO2 which corresponds to 60 ppb CO2 of dissolved carbon dioxide. A soluble Teflon derivative with an extraordinarily high gas permeability was chosen as a protective coating to eliminate interferences by ionic species like chloride or pH. Response times of less than 1 min were observed. The performance of the new microsensor is described with respect to reproducibility of the calibration curves, dynamic range, temperature behavior, long term stability and storage stability. The effect of hydrogen sulfide as an interferent, which is frequently present in anaerobic sediment layers, was studied in detail. PMID- 11220344 TI - Analysis of low molecular weight organic acids in water with capillary zone electrophoresis employing indirect photometric detection. AB - A capillary zone electrophoretic method for the analysis of low molecular weight carboxylic acids in water was developed. The application uses the chromophore trimellitic acid that allows for indirect photometric detection at 254 nm. Selectivity control by the addition of Ca2+ to the carrier electrolyte made possible a baseline resolved separation of 14 carboxylic acids. Good linearity and repeatability were obtained for both electrokinetic and hydrostatic injection modes. The usefulness of the method is demonstrated by the analysis of a snow sample. PMID- 11220345 TI - Determination of Al, Cu, Li and Mn in spruce seeds and plant reference materials by slurry sampling graphite furnace atomic absorption spectrometry. AB - An ultrasonic slurry sampling graphite furnace AAS method was developed for the determination of Al, Cu, Li and Mn in spruce seeds, NBS SRM 1575 pine needles and GBW CRM 07602 bush branches and leaves. The only sample preparation was grinding in a Mixer Mill before preparing a slurry by adding 0.14 mol/L nitric acid to a small sample aliquot. Cryogenic grinding was used for the spruce seeds to solve the problem of agglomerating during grinding at room temperature. A modified sample tray was applied allowing the use of both the commercial 1.5 mL vials and home-made 15 mL vials. With optimal conditions for ultrasonic agitation the homogeneity and particle size distributions in the slurries prepared in the two different vials were similar. Several aspects of the slurry sampling approach are discussed and data of important parameters are given, including the total number of particles injected into the graphite furnace, densities of the materials and percentage of analyte extracted into the liquid phase of the slurry. The density of the materials was determined by two methods; by using a Coulter particle analyser and by using a gravimetric method. The two methods gave similar accuracy and precision. The concentration ranges of the elements (in microg g(-1)) were: 80-2100 for Al, 3-15 for Cu, 0.06-2.5 for Li and 50-700 for Mn. External calibration with aqueous standards was employed. Chemical modifiers were not found to be necessary. The relative standard deviations were in the range 1.7-7%. Analyses of the two certified plant reference materials confirmed the accuracy of the method. In addition no significant difference was found for analyses of digested and slurried spruce seeds. The detection limit was 10 ng g(-1) for Li and 170 ng g(-1) for Cu. The characteristic mass (area measurements) was 4.4 pg for Li and 11 pg for Cu. For Al and Mn less sensitive wavelengths were used. PMID- 11220346 TI - Cationic cyanine as a near-infrared fluorescent probe for the determination of nucleic acids. AB - A new method with a cationic near-IR cyanine as fluorescent probe was developed for the determination of nucleic acids. The near-IR cyanine shows maximum excitation and emission wavelengths at 765 and 790 nm, respectively, in aqueous solution. The method is based on the fluorescence decrease of near-IR cyanine in the presence of nucleic acids. Under optimal conditions, the ratio of fluorescence intensity in the absence and presence of nucleic acids was proportional to the concentration of nucleic acids over the range 0.10-1.2 microg/mL for CT (calf thymus) DNA or SM (salmon sperm) DNA, and 0.10-1.6 microg/mL for yeast RNA. The detection limits were 30 ng/mL for CT DNA, 25 ng/mL for SM DNA and 70 ng/mL for yeast RNA. The relative standard deviation (n = 6) was 2.1% for 500 ng/mL CT DNA, 2.4% for 500 ng/mL SM DNA and 2.7% for 500 ng/mL yeast RNA, respectively. PMID- 11220347 TI - New strategy for the determination of microcystins and diarrhetic shellfish poisoning (DSP) toxins, two potent phosphatases 1 and 2A inhibitors and tumor promoters. AB - A new analytical strategy was established to improve the determination and identification performance during analyses of microcystins and diarrhetic shellfish poisoning (DSP) toxins in different matrices. Automated high performance size exclusion chromatography (gel permeation chromatography, SEC) was applied for the clean-up of raw extracts from algae and mussel tissue containing either microcystins or DSP toxins. The cleaned raw extracts are well suited for the direct determination of microcystins and DSP toxins by HPLC/MS. The analyses of cleaned raw extracts containing microcystin by HPLC and UV/diode array detection (DAD) revealed chromatograms without interfering peaks. Additionally, methods for the identification of unknown microcystins and those not available as standards were developed and established. The proposed strategy is exemplarily demonstrated for the analyses of a natural algae community from a lake in Slowakia and a naturally contaminated mussel from Portugal. PMID- 11220348 TI - HOPE for diabetes in the new millennium. Heart Outcomes Prevention Evaluation. PMID- 11220350 TI - Sulphonylurea dose-response relationships: relation to clinical practice. PMID- 11220349 TI - Is there a role for endothelin antagonists in diabetic renal disease? PMID- 11220351 TI - Effects of inhibition of the renin-angiotensin system on the cardiovascular actions of insulin. PMID- 11220352 TI - Treatment of familial hypertriglyceridaemia with acarbose. AB - AIM: The evaluation of serum triglyceride levels has played an important role as an independent method for assessing the risk factor for coronary atherosclerosis. Fibrates, nicotinic acid, and omega-3 polyunsaturated fish oils are the pharmacological tools most used today against hypertriglyceridaemia. Acarbose is a pseudotetrasaccharide of microbial origin which exerts a competitive, selective and reversible inhibition of the intestinal alpha glucoside-hydrolase. We evaluated the efficacy and side-effects of acarbose as a new and alternative drug in the treatment of hypertriglyceridaemia in non-diabetic patients. METHODS: We enrolled 30 non-diabetic patients (18 men, 12 women; mean age 59.23 +/- 6.27 years) without a family history of diabetes mellitus affected by familial hypertriglyceridaemia. The study covered a total period of 6.5 months: half of the patients were on 1.5 months of 'run in' diet only followed by 5 months of therapeutic diet plus acarbose; and half were on the therapeutic diet plus placebo. We gave 30 dividable pills to all patients. The administration was as follows: half a pill before lunch and half a pill before dinner while on the 'run in' diet. Fifteen patients (group A) took acarbose while the reminder (group B) took a placebo (50 mg of starch); these were distributed randomly and the test was double blind. The 20 weeks of study were divided in five 4-week periods. Fasting serum concentrations of total cholesterol, triglycerides, HDL-cholesterol (HDL-c), LDL-cholesterol (LDL-c) and glucose were determined at the starting of the study and after each treatment cycle. Glucose values were determined 2 h after lunch at the beginning of the study and at the end of the first, third and fifth month of treatment. All parameters assessed have been analysed by anova. RESULTS: The serum total cholesterol, LDL-c levels observed in the two groups did not change during the course of treatment. We observed a noteworthy progressive reduction of mean baseline triglyceride levels until the fourth month (p < 0.05) in acarbose-treated patients, with an increase in HDL-c (p < 0.008). CONCLUSIONS: We maintain that acarbose may be a useful therapeutic tool in addition to the diet in order to reduce triglyceride serum levels in non-diabetic patients. PMID- 11220353 TI - Factors associated with nocturnal hypoglycaemia among patients with type 2 diabetes new to insulin therapy: experience with insulin lispro. AB - AIM: To identify factors associated with nocturnal hypoglycaemia in patients with type 2 diabetes who were new (< 2 months therapy) to insulin therapy. METHODS: A randomised, multicentre, 12-month parallel open-label study compared the clinical safety and efficacy of insulin lispro with regular human insulin. A cohort of North American patients completed a health-related quality of life (HRQOL) questionnaire which included questions related to the Health Beliefs Model (HBM). Measurements of hypoglycaemia rate and short-and long-term glucose control assessed clinical safety and efficacy. Three hundred and sixty-five type 2 diabetic patients were enrolled in the study, and 195 North American patients completed the HRQOL questionnaire. RESULTS: After adjustment for demographic and psychological factors, the study population demonstrated lower nocturnal hypoglycaemia risk with insulin lispro. Higher nocturnal hypoglycaemia risk was associated with reduced body mass index (b.m.i.), lower age, and basal ultralente insulin therapy. The associated hypoglycaemia risk was lower with increased alcohol consumption. Patients who completed the HRQOL survey demonstrated higher risk for nocturnal hypoglycaemia if they: (1) had more troublesome hyperglycaemia symptoms in the week before starting insulin; (2) were more confident in their ability to control their diabetes; or (3) thought that diabetes control did not offer a clear health benefit. Nocturnal hypoglycaemia risk was inversely associated with fear of hypoglycaemia. CONCLUSIONS: Type 2 diabetic patients new to insulin therapy demonstrated lower risk of nocturnal hypoglycaemia with insulin lispro. Practitioners should consider patient characteristics and psychological factors that may predispose type 2 diabetes patients to nocturnal hypoglycaemia when initiating insulin therapy. PMID- 11220354 TI - Time-course changes in plasma endothelin-1 and its effects on the mesenteric arterial bed in streptozotocin-induced diabetic rats. AB - AIM: To examine the mechanisms underlying the elevated plasma endothelin-1 (ET-1) in diabetes and its vascular effects. RESULTS: Relationships between the plasma ET-1 level and the levels of other plasma constituents (glucose, cholesterol, and triglyceride) were found in 10-week streptozotocin (STZ)-induced diabetic rats. In contrast, at 1 week after the STZ injection only plasma ET-1 and glucose levels were elevated, suggesting that the hyperglycaemia might trigger the excess production of ET-1. Incubation with high glucose promoted the release of ET-1 from the isolated mesenteric arterial bed. In STZ-induced diabetic rats, the maximum contractile response of the mesenteric arterial bed to ET-1 was significantly reduced, and the vasoconstriction and vasodilation induced by the ET(B)-receptor agonist IRL-1620 in this bed were significantly impaired. The vascular responses induced by these ET receptor agonists were restored to normal by chronic treatment of diabetic rats with insulin for 7 or 4 weeks. CONCLUSIONS: These results suggest: (1) that the marked increase in plasma glucose in STZ induced diabetic rats elevates the plasma ET-1; and (2) that the decreased contractile and vasodilator responses of the mesenteric arterial bed to ET-1 receptor agonists may be due to desensitization of not only ET(A), but also ET(B) receptors, an effect secondary to the elevation of plasma ET-1. PMID- 11220355 TI - Dissociation between Fas expression and induction of apoptosis in human islets of Langerhans. AB - There is increasing evidence that inappropriate induction of apoptosis in pancreatic beta-cells may precede the development of type 1 diabetes in animal models and in man. One mechanism by which this has been proposed to occur involves up-regulation of the death receptor Fas on beta-cells, resulting in apoptosis of the Fas-bearing beta-cells upon ligation of the receptor. We have examined this hypothesis in isolated human islets of Langerhans and show that--in contrast to data obtained with rodent beta-cells--expression of Fas per se is not sufficient to allow induction of apoptosis upon addition of agonistic anti-Fas serum. PMID- 11220356 TI - Near-syncope and abnormal T waves in a young woman. PMID- 11220357 TI - Delirium: a barometer for quality of hospital care. PMID- 11220358 TI - Current management of rheumatoid arthritis. PMID- 11220359 TI - Eating disorders: 1. anorexia nervosa. AB - Although many of the factors that contribute to anorexia nervosa are not within the physician's control, early detection and prompt initiation of treatment may improve patient outcome. A high level of suspicion and a willingness to address the issue can serve our patients well. PMID- 11220360 TI - New perspectives on pneumococcal meningitis. PMID- 11220361 TI - Verapamil block of large-conductance Ca-activated K channels in rat aortic myocytes. AB - The effects of verapamil on the large conductance Ca-activated K (BK) channel from rat aortic smooth muscle cells were examined at the single channel level. Micromolar concentrations of verapamil produced a reversible flickering block of the BK channel activity. Kinetic analysis showed that verapamil decreased markedly the time constants of the open states, without any significant change in the time constants of the closed states. The appearance of an additional closed state-specifically, a nonconducting, open-blocked state--was also observed, whose time constant would reflect the mean residence time of verapamil on the channel. These observations are indicative of a state-dependent, open-channel block mechanism. Dedicated kinetic (group) analysis confirmed the state-dependent block exerted by verapamil. D600 (gallopamil), the methoxy derivative of verapamil, was also tested and found to exert a similar type of block, but with a higher affinity than verapamil. The permanently charged and membrane impermeant verapamil analogue D890 was used to address other important features of verapamil block, such as the sidedness of action and the location of the binding site on the channel protein. D890 induced a flickering block of BK channels similar to that observed with verapamil only when applied to the internal side of the membrane, indicating that D890 binds to a site accessible from the cytoplasmic side. Finally, the voltage dependence of D890 block was assessed. The experimental data fitted with a Langmuir equation incorporating the Woodhull model for charged blockers confirms that the D890-binding site is accessed from the internal mouth of the BK channel, and locates it approximately 40% of the membrane voltage drop along the permeation pathway. PMID- 11220362 TI - An integrated view of the kinetics of glucose and phosphate transport, and of glucose 6-phosphate transport and hydrolysis in intact rat liver microsomes. AB - The dynamics of the glucose 6-phosphatase system were investigated in intact rat liver microsomes using a fast-sampling, rapid-filtration apparatus. Glucose and phosphate transport followed single exponential kinetics, appeared to be homogeneous, was unaffected by unlabeled substrate concentrations up to 100 mM, proved insensitive to various potential inhibitors, and demonstrated similarly low energies of activation. The extent of tracer accumulation from glucose 6 phosphate depended on which of the glucose or phosphate moieties was the labeled species in the parent molecule. The rates of tracer equilibration reflected those of glucose or phosphate transport but similar initial rates of uptake were observed for the glucose and phosphate products of hydrolysis. However, the latter accounted for only 12-13% of the steady-state rate of total glucose production. It is concluded that tracer uptake cannot represent substrate transport, that labeled glucose 6-phosphate at best represents a tiny fraction of the intramicrosomal glucose or phosphate pools, and that glucose 6-phosphate transport is not an obligatory prerequisite to its hydrolysis. The latter conclusion invalidates a major postulate of the substrate transport-catalytic unit concept but proves compatible with a conformational model whereby glucose 6 phosphate transport and hydrolysis are tightly coupled processes while glucose and phosphate share, along with water and a variety of other organic and inorganic solutes, a common porelike structure for their transport through the microsomal membrane. PMID- 11220363 TI - Characterization of the ryanodine receptor-Ca2+ release channel from the thoracic tissues of the lepidopteran insect Heliothis virescens. AB - The existence of invertebrate forms of the RyR has recently been confirmed (Takeshima et al., 1994, Puente et al., 2000). However, information on the functional properties of this insect RyR is still limited. We report the functional characterization of a RyR from the thoracic muscle of H. virescens (Scott-Ward et al., 1997). A simple purification protocol produced membranes from homogenized prefrozen H. virescens thoracic muscle with a [3H]-ryanodine binding activity of 1.19 +/- 0.21 pmol/mg protein (mean +/- SE; n = 4). [3H]-Ryanodine binding to the H. virescens receptor was dependent on the ryanodine concentration in a hyperbolic fashion with a KD of 3.82 nM (n = 4). [3H]-ryanodine binding was dependent on [Ca2+] in a biphasic manner and was stimulated by 1 mM ATP. Millimolar caffeine did not stimulate [3H]-ryanodine binding to H. virescens membranes in the presence of either nanomolar or micromolar Ca2+. A protein of at least 400 KDa was recognized in H. virescens membrane proteins by a specific anti H. virescens RyR antibody. Discontinuous density sucrose gradient fractionation of microsomal membranes produced vesicles suitable for single-channel studies. Ca2+-sensitive, Ca2+-permeable channels were successfully inserted into artificial lipid bilayers from H. virescens membrane vesicles. The H. virescens RyR-channel displayed a Ca2+ conductance of approximately 110 pS and underwent a persistent and characteristic modification of ion handling and gating following addition of 100 nM ryanodine. The gating of H. virescens channels was sensitive to ATP and ruthenium red in a manner similar to mammalian RyR. This is the first report to describe the single channel and [3H]-ryanodine binding properties of a native insect RyR. PMID- 11220364 TI - Functional asymmetry of the sodium-D-glucose cotransporter expressed in yeast secretory vesicles. AB - The sodium-D-glucose cotransporter (SGLT1) was expressed in a yeast mutant strain NY 17 (sec6-4) that accumulates secretory vesicles at a nonpermissive temperature because of a block in the delivery of these vesicles to the plasma membrane. By differential centrifugation a microsomal fraction enriched in secretory vesicles was prepared with a high specific activity of the vanadate-sensitive H+-ATPase and invertase. In this membrane fraction one protein band of an apparent molecular weight of 55 kDa representing the nonglycosylated SGLT1 protein could be detected by immunochemical analysis. In addition, higher molecular weight protein bands probably representing dimers and aggregates were found. In transport studies with the microsomes D-glucose fluxes showed asymmetric properties: efflux experiments revealed the typical properties of the SGLT1 such as sodium dependence, inhibition by phlorizin and potential dependence. Influx of D-glucose showed no dependence on sodium and was not inhibited by phlorizin. Furthermore, the transporter exhibited a striking asymmetry with regard to the D glucose affinity and the sugar specificity. These results suggest that the orientation of the SGLT1 expressed in yeast secretory vesicles is, indeed, inverted with regard to its configuration in the plasma membrane of epithelial cells. Moreover, there are striking functional differences between the periplasmic and cytoplasmic face of the transporter. PMID- 11220365 TI - Cloning and function of the rat colonic epithelial K+ channel KVLQT1. AB - KVLQT1 (KCNQ1) is a voltage-gated K+ channel essential for repolarization of the heart action potential that is defective in cardiac arrhythmia. The channel is inhibited by the chromanol 293B, a compound that blocks cAMP-dependent electrolyte secretion in rat and human colon, therefore suggesting expression of a similar type of K+ channel in the colonic epithelium. We now report cloning and expression of KVLQT1 from rat colon. Overlapping clones identified by cDNA library screening were combined to a full length cDNA that shares high sequence homology to KVLQT1 cloned from other species. RT-PCR analysis of rat colonic musoca demonstrated expression of KVLQT1 in crypt cells and surface epithelium. Expression of rKVLQT1 in Xenopus oocytes induced a typical delayed activated K+ current, that was further activated by increase of intracellular cAMP but not Ca2+ and that was blocked by the chromanol 293B. The same compound blocked a basolateral cAMP-activated K+ conductance in the colonic mucosal epithelium and inhibited whole cell K+ currents in patch-clamp experiments on isolated colonic crypts. We conclude that KVLQT1 is forming an important component of the basolateral cAMP-activated K+ conductance in the colonic epithelium and plays a crucial role in diseases like secretory diarrhea and cystic fibrosis. PMID- 11220366 TI - Cell surface area regulation and membrane tension. AB - The beautifully orchestrated regulation of cell shape and volume are central themes in cell biology and physiology. Though it is less well recognized, cell surface area regulation also constitutes a distinct task for cells. Maintaining an appropriate surface area is no automatic side effect of volume regulation or shape change. The issue of surface area regulation (SAR) would be moot if all cells resembled mammalian erythrocytes in being constrained to change shape and volume using existing surface membrane. But these enucleate cells are anomalies, possessing no endomembrane. Most cells use endomembrane to continually rework their plasma membrane, even while maintaining a given size or shape. This membrane traffic is intensively studied, generally with the emphasis on targeting and turnover of proteins and delivery of vesicle contents. But surface area (SA) homeostasis, including the controlled increase or decrease of SA, is another of the outcomes of trafficking. Our principal aims, then, are to highlight SAR as a discrete cellular task and to survey evidence for the idea that membrane tension is central to the task. Cells cannot directly "measure" their volume or SA, yet must regulate both. We posit that a homeostatic relationship exists between plasma membrane tension and plasma membrane area, which implies that cells detect and respond to deviations around a membrane tension set point. Maintenance of membrane strength during membrane turnover, a seldom-addressed aspect of SA dynamics, we examine in the context of SAR. SAR occurs in both animal and plant cells. The review shows the latter to be a continuing source of groundbreaking work on tension-sensitive SAR, but is principally slanted to animal cells. PMID- 11220367 TI - Review of medical prevention of vasospasm after aneurysmal subarachnoid hemorrhage: a problem of neurointensive care. AB - Cerebral vasospasm remains a devastating medical complication of aneurysmal subarachnoid hemorrhage (SAH). It is associated with high morbidity and mortality rates, even after the aneurysm has been secured surgically or radiologically. A great deal of experimental and clinical research has been conducted in an effort to find ways to prevent this complication. The literature includes extensive coverage of in vivo animal model studies of SAH and vasospasm. These experimental studies have contributed to tremendous advances in the understanding of the mechanisms leading to cerebral vasospasm. Most of the experimental settings, however, have demonstrated varying levels of ability to predict accurately what occurs in human SAH. Therefore, although animal models have been developed to test new therapies, most of the treatment effects have been shown to be less compelling when trials have been conducted in clinical settings. The interpretation of current literature is complicated further by the imprecise estimation of the incidence of cerebral vasospasm, which is due to various degrees of clinical expression, ranging from the absence of symptoms in the presence of increased blood flow velocities at transcranial Doppler or vessel diameter reduction at angiography to neurological manifestations of severe ischemic deficits. In addition, a change over time in the incidence pattern of human SAH and vasospasm, possibly related to improved surgical techniques and overall patient management, may have occurred. This topic review collects the relevant literature on clinical trials investigating prophylactic therapies for cerebral vasospasm in patients with aneurysmal SAH and emphasizes the need for large clinical trials to confirm the results derived from clinical experience. In addition, it points out some experimental therapies that may hold promise in future clinical trials to prevent the occurrence of vasospasm. PMID- 11220368 TI - Pallidotomy: a comparison of responders and nonresponders. AB - OBJECTIVE: We reviewed a prospective series of 32 unilateral, large-volume, microelectrode-guided posteroventral pallidotomies to determine the differences between responsive and nonresponsive patients. METHODS: Our patients underwent extensive pre- and postoperative evaluations. One year postoperatively, we correlated the outcomes of 25 patients with their histories, physical findings, neuropsychological assessments, and lesion characteristics to further understand the indications, limitations, and pitfalls of unilateral pallidotomy. Our group judged responsiveness by comparing the preoperative total Unified Parkinson's Disease Rating Scale off-state scores with those obtained 1 year postoperatively. A score indicating greater than 20% improvement at 1-year follow-up was rated a good outcome; improvement of greater than 40% was rated an excellent outcome. RESULTS: Although most patients sustained long-term benefits, some demonstrated little or no improvement. Patient and lesion factors influenced outcome. Younger age (<60 yr), tremor, unilateral predominance, L-dopa responsiveness, motor fluctuations with dyskinesia, and good lesion placement predicted a good response to unilateral pallidotomy. Advanced age (>70 yr), absence of tremor, increased duration of disease, reduced responsiveness to L-dopa, frontal behavioral changes, prominent apraxic phenomena, and improper lesion placement predicted a poor response. CONCLUSION: Unilateral, large-volume pallidotomy with precise lesion control provides long-lasting benefits for carefully selected patients. PMID- 11220369 TI - Quantitative and qualitative outcome measures after thalamic deep brain stimulation to treat disabling tremors. AB - OBJECTIVE: We studied outcome measures after unilateral and bilateral thalamic stimulation to treat disabling tremor resulting from essential tremor and Parkinson's disease. The surgical technique, qualitative and quantitative tremor assessments, stimulation parameters, locations of active electrodes, complications, and side effects are described and analyzed. METHODS: Forty-one patients with essential tremor or Parkinson's disease underwent implantation of 56 thalamic stimulators. Preoperative qualitative and quantitative tremor measurements were compared with those obtained after unilateral and bilateral surgery, with activated and deactivated stimulators. Stimulation parameters and stimulation-related side effects were recorded, and outcome measures were statistically analyzed. RESULTS: Qualitative measurements demonstrated significant improvement of contralateral upper-limb (P < 0.001), lower-limb (P < 0.01), and midline (P < 0.001) tremors after unilateral surgery. Ipsilateral arm tremor also improved (P < 0.01). No differences were observed with the Purdue pegboard task. Quantitative accelerometer measurements were correlated with qualitative assessments and confirmed improvements in contralateral resting (P < 0.001) and postural (P < 0.01) tremors and ipsilateral postural tremor (P < 0.05). Activities of daily living improved after unilateral surgery (P < 0.001) and additionally after bilateral surgery (P < 0.05). Adjustments of the pulse generator were required more frequently for tremor control than for amelioration of side effects. Bilateral thalamic stimulation caused more dysarthria and dysequilibrium than did unilateral stimulation. Stimulation-related side effects were reversible for all patients. Stimulation parameters did not change significantly with time. A significantly lower voltage and greater pulse width were used for patients with bilateral implants. CONCLUSION: Unilateral thalamic stimulation and bilateral thalamic stimulation are safe and effective procedures that produce qualitative and quantitative improvements in resting, postural, and kinetic tremor. Thalamic stimulation-related side effects are mild and reversible. PMID- 11220370 TI - Long-term tumor control and functional outcome in patients with cavernous sinus meningiomas treated by radiotherapy with or without previous surgery: is there an alternative to aggressive tumor removal? AB - OBJECTIVE: We report the long-term follow-up of 31 patients with cavernous sinus meningiomas who were treated either with surgery and radiotherapy (RT) or with RT alone. This retrospective review was undertaken to compare long-term efficacy and morbidity of RT with or without previous surgery versus complete, aggressive surgical removal. METHODS: Between 1980 and 1997, we performed a retrospective study of 31 patients harboring cavernous sinus meningiomas. The patient group comprised 25 women and 6 men. Patients were divided into two therapeutic categories: patients treated with surgery and RT (Group I, 17 patients) and patients treated with RT alone (Group II, 14 patients). Twenty-five patients (14 in Group I and 11 in Group II) were treated for primary tumors, and 6 patients (3 in Group I and 3 in Group II) were treated for recurrent disease. All three patients who were treated by RT alone at the time of recurrent disease had had previous surgery as initial treatment. Tumor control, treatment morbidity, and functional outcomes were evaluated for all patients. Twenty-eight patients were alive at the time of analysis, with a median follow-up period of 6.1 years. RESULTS: The progression-free survival rate was 92.8% at 10-year follow-up. Only two patients exhibited tumor progression after initial treatment. One of the patients who experienced tumor regrowth 4 years after surgery and RT benefited from additional conventional external beam radiation, and this patient exhibited no evidence of tumor progression at the last follow-up examination 6 years later. Two patients experienced cranial nerve impairment after surgery, and no patients developed late radiation toxicity. Follow-up status as measured by the Karnofsky Performance Scale deteriorated in 7% of patients and was the same or improved in 93% of patients. CONCLUSION: The results of combined surgery and RT or RT alone indicated a high rate of tumor control and a low risk of complications. Complete aggressive surgical removal of cavernous sinus meningiomas is associated with an increased incidence of morbidity and mortality and does not demonstrate a better rate of tumor control. Conventional external beam radiation seems to be an efficient and safe initial or adjuvant treatment of these lesions, and these findings should serve as a basis for evaluating new alternatives such as radiosurgery or stereotactic RT. PMID- 11220371 TI - Secretory meningiomas: clinical and immunohistochemical observations. AB - OBJECTIVE: Secretory meningiomas are a rare histological subtype of these benign intracranial tumors. Few reports have been published regarding their tendency to develop peritumoral edema. METHODS: Between July 1994 and February 1999, 11 patients with secretory meningiomas underwent operations in the Department of Neurosurgery, University of Kiel, Kiel, Germany. The clinical notes and radiological data (computed tomographic and magnetic resonance imaging scans) were reviewed. Immunohistochemistry was used to examine the expression of carcinoembryonic antigen and epithelial membrane antigen as well as progesterone and estrogen receptors. RESULTS: Secretory meningiomas were found in 11 (5%) of 214 patients with intracranial meningiomas who were operated on in that period. All 11 patients were women. These patients' mean age was 65 years (range, 51-87 yr). The localization of these tumors was at the convexity in seven patients, at the sphenoid ridge in two patients, and in the olfactory groove and petroclival region in one patient each. Two meningiomas had no edema surrounding them, two meningiomas had a small amount of edema, two had moderate edema, and five had severe edema. No recurrences were observed during the mean follow-up period of 26 months (range, 8-65 mo). Immunohistochemically, all tumors contained pseudopsammoma bodies and reacted with epithelial membrane antigen and carcinoembryonic antigen. The MIB-1 antibody staining index showed a mean of 2% (range, 0-7%). CONCLUSION: Secretory meningiomas are rare tumors, and they are mainly localized at the frontal convexity and the sphenoid ridge. They are surrounded by more edema than usual. The preponderance of female patients with this presentation is striking. The expression of carcinoembryonic antigen and epithelial membrane antigen is a characteristic feature of secretory meningiomas. These meningiomas are also positive for progesterone receptors, which has been shown to be a good prognostic factor. PMID- 11220372 TI - Choroid plexus tumors in children: significance of stromal invasion. AB - OBJECTIVE: A group of choroid plexus tumors fit the cellular criteria for choroid plexus papilloma (CPP) except for invasion into the adjacent parenchyma, with associated loss of the normal villus architecture at the site of invasion. These tumors retain a benign cellular appearance. In the existing literature, it is unclear whether these tumors are classified as choroid plexus carcinomas or as CPPs. In our experience, although evidence of invasion is present, these tumors tend to exhibit benign behavior. We suggest that stromal invasion of this type remains consistent with a benign clinical course, although surgical results may demonstrate higher morbidity rates, given the invasive nature of the tumors. The failure to classify these tumors as CPPs may explain some of the variability in outcomes reported for various studies. METHODS: To study this question, clinical and histological data for children diagnosed with CPPs (either with or without stromal invasion) between 1985 and 1995 were examined. Only cases with pre- and postoperative magnetic resonance imaging data were included in the series. RESULTS: A total of 12 patients with CPPs were identified, with 4 tumors being notable for stromal invasion. After gross total tumor removal, none of the eight children with CPPs received adjuvant therapy at our institution; all are alive without evidence of tumor recurrence after surgical excision (mean, 108 mo). Of the four patients with stromal invasion, three underwent gross total resection. The one patient who underwent subtotal resection received chemotherapy at another facility. All four of these patients are alive, after a mean of 100 months of follow-up monitoring. CONCLUSION: It is recommended that CPPs with a benign cellular appearance but with evidence of local parenchymal invasion and loss of the normal villus architecture at the site of invasion be classified as CPPs. Patients with these tumors respond to surgical therapy alone, without the need for adjuvant treatment. PMID- 11220373 TI - Prodromal signs and clinical factors influencing outcome in patients with intraventricular rupture of purulent brain abscess. AB - OBJECTIVE: To elucidate prodromal signs and clinical factors influencing the prognosis in patients with intraventricular rupture of brain abscess (IVROBA) to prevent and manage this catastrophic condition. METHODS: In this study, 33 consecutive patients with IVROBA diagnosed by computed tomography (CT) were treated. Basic and therapeutic parameters were evaluated as independent predictive factors of a poor prognosis by using univariate analysis. The factors were statistically analyzed based on the interval between initial symptoms and IVROBA. RESULTS: Patients with a good outcome were younger (<21 yr old) (P < 0.003) and had fewer complications after IVROBA (P < 0.03). For the most part, these patients had undergone aspiration for brain abscess with ventricular drainage combined with the immediate administration of appropriate intravenous and intrathecal antibiotics (P < 0.02). In just a short time, abscesses located in the parieto-occipital region ruptured into the ventricle (P < 0.004), and those with nonsterile cultures (P < 0.01) developed into IVROBA. Just before IVROBA, patients had severe headaches, signs of meningeal irritation, and a rapidly deteriorating clinical condition within 10 days after the signs of meningeal irritation developed. A CT scan obtained before IVROBA ascertained localized enhancement of the ventricular wall adjacent to the abscess. CONCLUSION: Our findings suggest that signs of meningeal irritation and localized enhancement of the ventricular wall adjacent to the abscess, as observed on CT scans, preceded IVROBA. To decrease the mortality rate associated with purulent brain abscesses, signs forewarning of IVROBA should be recognized, and aggressive management of IVROBA should be initiated. Aggressive CT-guided aspiration of deep seated abscesses, particularly in the parieto-occipital region, at the time forewarning signs of IVROBA are observed lead to the prevention of IVROBA and an improvement in outcome. PMID- 11220374 TI - Utility of three-dimensional computed tomographic angiography for assessment of relationships between the vertebrobasilar system and the cranial base. AB - OBJECTIVE: The optimal surgical exposure for basilar tip aneurysms is dictated by the relationship of the basilar bifurcation to the cranial base. This study was designed to evaluate three-dimensional computed tomographic angiography as a means of obtaining detailed anatomic information on the basilar artery and the surrounding cranial base in individual patients before surgery. METHODS: We studied 30 patients using three-dimensional computed tomographic angiographic reconstructions from 1-mm computed tomographic slices. Detailed anatomic measurements were performed to define the relationship between the basilar artery and the cranial base. Particular attention was paid to the height of the dorsum sellae and its relationship to the basilar bifurcation. RESULTS: The heights of the basilar apex and the vertebrobasilar junction, relative to the cranial base, were extremely variable. Considerable asymmetries in the heights of the left and right posterior clinoid processes were identified; in one case, this difference was more than 1 cm (mean difference in height, 0.9 mm; range, 0-10.3 mm). The heights of the posterior clinoid processes above the sellar floor ranged from 5.8 to 14.1 mm (mean height, 9.5 mm). We were able to determine the feasibility of the pterional/orbitozygomatic, middle fossa/ anterior petrosal, and presigmoid retrolabyrinthine approaches to an individual basilar bifurcation. We also estimated the amount of bone removal required and determined the operative distances via those approaches. CONCLUSION: Three-dimensional computed tomographic angiography is a useful tool for assessing critical anatomic relationships and represents an adjunct to conventional angiography in the planning of individualized, precisely tailored, cranial base approaches to the vertebrobasilar system. PMID- 11220375 TI - Effect of carotid endarterectomy on chronic ocular ischemic syndrome due to internal carotid artery stenosis. AB - OBJECTIVE: We evaluated the effect of carotid endarterectomy on chronic ocular ischemic syndrome due to internal carotid artery stenosis by use of data obtained from ophthalmic artery color Doppler flow imaging. METHODS: We examined 11 patients with ocular ischemic syndrome due to internal carotid artery stenosis (>70% stenosis) who were being treated by carotid endarterectomy. Ophthalmic artery color Doppler flow imaging indicated ophthalmic artery flow direction and peak systolic flow velocity and was performed before and at 1 week, 1 month, and 3 months after surgery. RESULTS: We assessed the ophthalmic arteries of 11 patients via color Doppler flow imaging. Before undergoing carotid endarterectomy, five patients showed reversed ophthalmic artery flow. In the other six patients who experienced antegrade ophthalmic artery flow, the average peak systolic flow velocity was 0.09 +/- 0.05 m/s (mean +/- standard deviation). Preoperative reversed flow resolved in each patient 1 week after undergoing surgery. All patients showed antegrade ophthalmic artery flow. The average peak systolic flow velocity in the patients who had preoperative antegrade flow rose significantly, to 0.21 +/- 0.14 m/s (P < 0.05). There was no significant change as compared with findings at 1 week after surgery. During the follow-up period (mean, 32.4 mo), no patients complained of recurrent visual symptoms. At the end of the study period, visual acuity had improved in five patients and had not worsened in the other six patients. CONCLUSION: Carotid endarterectomy was effective for improving or preventing the progress of chronic ocular ischemia caused by internal carotid artery stenosis. PMID- 11220376 TI - Anterior lumbar microdiscectomy and interbody fusion for the treatment of recurrent disc herniation. AB - OBJECTIVE: To demonstrate the feasibility of anterior lumbar microdiscectomy in patients with recurrent, sequestered lumbar disc herniations. METHODS: Between 1997 and 1999, six patients underwent a muscle-sparing "minilaparotomy" approach and subsequent microscopic anterior lumbar microdiscectomy and fragmentectomy for recurrent lumbar disc extrusions at L5-S1 (n = 4) or L4-L5 (n = 2). A contralateral distraction plug permitted ipsilateral discectomy under microscopic magnification. Effective resection of the extruded disc fragments was accomplished by opening the posterior longitudinal ligament. Interbody fusion was performed by placing cylindrical threaded titanium cages (n = 4) or threaded allograft bone dowels (n = 2). RESULTS: There were no complications, and blood loss was minimal. Follow-up magnetic resonance imaging revealed complete resection of all herniated disc material. Plain x-rays revealed excellent interbody cage position. Radicular pain and neurological deficits resolved in all six patients (mean follow-up, 14 mo). CONCLUSION: Anterior lumbar microdiscectomy with interbody fusion provides a viable alternative for the treatment of recurrent lumbar disc herniations. Recurrent herniated disc fragments can be removed completely under direct microscopic visualization, and interbody fusion can be performed in the same setting. PMID- 11220377 TI - Nuances of middle cerebral artery aneurysm microsurgery. AB - Middle cerebral artery aneurysms, a common source of subarachnoid hemorrhage, occur predominantly at the main bifurcation of the middle cerebral artery. Microsurgical clipping is the most effective treatment of these aneurysms because of their peripheral location, wide necks, and straightforward surgical anatomy. Despite the moderate technical requirements of this type of surgery, patients with ruptured aneurysms often have poor outcomes because of the high incidence of intracerebral hematomas. Although several different surgical approaches can be used, we favor a lateral-to-medial transsylvian approach for most aneurysms. This description of our surgical technique stresses minimizing retraction to avoid injury to the brain and preparing broad-based middle cerebral artery aneurysms for clipping. Management of outcomes when using these techniques also is presented. PMID- 11220378 TI - Transorbital keyhole approach to anterior communicating artery aneurysms. AB - OBJECTIVE: The transorbital keyhole approach to anterior communicating artery aneurysms was developed as a minimally invasive method for safe control of the anterior communicating artery complex. This approach does not necessitate resection of the gyrus rectus. METHODS: The technique is described in detail. The transorbital keyhole approach provides more ventral access than the supraorbital approaches, and the anterior communicating artery complex can be controlled by splitting the basal aspect of the interhemispheric fissure. RESULTS: Since late 1998, the authors have used the transorbital keyhole approach routinely. During the initial experience with 33 patients, the only observed complication specific to this approach was transient diplopia in one patient. At follow-up examinations 2 to 15 months after surgery, the cosmetic results were favorable as compared with those of standard pterional craniotomy. CONCLUSION: We have designed a small, custom-tailored approach to the anterior communicating artery complex for routine use. The small orbitocranial approach is a step toward the ideal of purely extra-axial safe control of anterior communicating artery aneurysms. The orbitocranial keyhole approach seems to be substantially better than the craniotomy, although it requires additional effort and time. PMID- 11220379 TI - Intratumoral arteriovenous shunting in malignant gliomas. AB - OBJECTIVE: Intratumoral arteriovenous shunting in glioblastomas has been suspected but neither proven nor quantified. METHODS: Using a previously described technique of selective intra-arterial intratumoral injection of 99mTc labeled microparticles (macroaggregated albumin), we measured the amount of radioactivity, by cerebral and pulmonary scintigraphy, in seven patients with malignant gliomas (six with glioblastomas and one with an anaplastic oligodendroglioma). The pulmonary shunt index was calculated as a percentage from the pulmonary/pulmonary plus cerebral radioactivity ratio. RESULTS: The results revealed a mean pulmonary shunt index of 67% (range, 47-89%), indicating that most of the microparticles injected into the tumor via the arterial route bypassed the tumor and reached the lungs. The measured arteriovenous shunting was greater when the injection was performed in an artery exclusively perfusing the tumor. CONCLUSION: Important intratumoral arteriovenous shunting exists in glioblastomas. The potential consequences of this finding for intra-arterial treatment strategies are discussed. PMID- 11220380 TI - Expression of endothelial cell angiogenesis receptors in human cerebrovascular malformations. AB - OBJECTIVE: To further understand the role of angiogenic growth factors in the development of cerebral cavernous malformations (CCMs) and arteriovenous malformations (AVMs), we investigated endothelial cell (EC) expression of receptors for vascular endothelial growth factor (VEGF) and angiopoietin systems in patients with surgically resected lesions. METHODS: Paraffin-embedded sections of five AVMs, CCMs, and normal control brain tissue samples were stained immunohistochemically with antibodies to von Willebrand factor and CD31 (to characterize ECs) and angiogenesis growth factor receptors Flt-1 (VEGF-R1), Flk-1 (VEGF-R2), Tie-1, and Tie-2. We counted large and small vessels in each specimen, assessed each specimen's immunoexpression of each antigen, and analyzed differences between CCMs, AVMs, and the normal control brain tissue samples. RESULTS: The ECs of CCMs, AVMs, and normal control brain tissue samples expressed the von Willebrand factor uniformly, but the ECs of CCMs were largely negative for CD31 (P < 0.05). Flk-1, Flt-1, and Tie-2 were not expressed in the control brain tissue samples. The proportion of immunopositive vessels to VEGF receptors Flk-1 and Flt-1 was significantly greater in AVMs and CCMs than in the control brain tissue samples (P < 0.05). Tie-2 in AVMs and CCMs was expressed in a higher percentage of immunopositive vessels than in the control brain tissue samples, but the difference was not statistically significant. Tie-1 was expressed in rare vessels of all lesion types and control brain tissue samples. CONCLUSION: ECs of CCMs do not seem to express CD31 to the same extent that AVMs and normal brain tissue do. AVMs and CCMs show greater expression of VEGF receptors, but not of angiopoietin receptors, than normal brain tissue does. PMID- 11220381 TI - Transcranial Doppler identification of changing autoregulatory thresholds after autoregulatory impairment. AB - OBJECTIVE: Transcranial Doppler (TCD) flow velocity (FV) assessment may provide a useful index of autoregulatory impairment after severe head injury. It may define a therapeutic end point against which cerebral perfusion pressure (CPP) can be titrated. This study examines the relationship between cerebral blood flow (CBF) and TCD FV indices in a laboratory model before and after autoregulatory impairment. METHODS: CPP, CBF, and middle cerebral artery TCD FV were measured continuously in nine anesthetized and ventilated sheep. CPP was decreased by hemorrhagic hypotension. The process was repeated after impairment of autoregulation by cisternal infusion, which maintained CPP at 0 mm Hg for 15 minutes. Points of significant change (i.e., breakpoints) from baseline values for each of the measured flow parameters were identified by using a ratio of variance technique. RESULTS: Before any significant change in CBF or systolic TCD, diastolic TCD FV decreased (mean breakpoint, 69 mm Hg; range, 56-78 mm Hg) as CPP was reduced. This divergence of diastolic and systolic TCD FV, which occurred before autoregulatory failure, was associated with an increasing TCD pulsatility index (mean breakpoint, 63 mm Hg; range, 53-70 mm Hg). At diastolic TCD FV congruent with 10 cm/s, systolic TCD FV (mean breakpoint, 48 mm Hg; range, 46-53 mm Hg) and CBF (mean breakpoint, 49 mm Hg; range, 47-51 mm Hg) decreased rapidly, indicating autoregulatory failure. After autoregulatory impairment, the breakpoints for all four indices shifted to higher CPP values (mean, 16 mm Hg). CONCLUSION: TCD FV assessment identified two CPP thresholds of autoregulatory loss. Before autoregulatory failure, an earlier phase of autoregulatory disturbance may be detected by divergent systolic and diastolic TCD FVs. It is important to note that this phase may be detected before CBF decreases. These TCD FV breakpoints depend on the state of autoregulatory impairment and may provide potential targets for CPP-directed therapy. PMID- 11220382 TI - Carbon dioxide reactivity and pressure autoregulation of brain tissue oxygen. AB - OBJECTIVE: To describe the normal relationships between brain tissue oxygen tension (PbrO2) and physiological parameters of systemic blood pressure and CO2 concentrations. METHODS: Licox Clark-type oxygen probes (GMS mbH, Kiel, Germany) were inserted in the frontal white matter of 12 swine maintained under general anesthesia with a 1.0 fraction of inspired oxygen (FiO2). In seven swine, alterations in end-tidal carbon dioxide (ET-CO2) concentration (range, 13-72 mm Hg) were induced via hyperventilation or instillation of CO2 into the ventilation circuit. In nine swine, mean arterial pressure (MAP) (range, 33-200 mm Hg) was altered; phenylephrine was used to induce hypertension, and a nitroprusside esmolol combination or systemic hemorrhage was used for hypotension. Quantitative cerebral blood flow (CBF) was measured in two animals by using a thermal diffusion probe. RESULTS: Mean baseline PbrO2 was 41.9 +/- 11.3 mm Hg. PbrO2 varied linearly with changes in ET-CO2, ranging from 20 to 60 mm Hg (r2 = 0.70). The minimum PbrO2 with hypocarbia was 5.9 mm Hg, and the maximum PbrO2 with hypercarbia was 132.4 mm Hg. PbrO2 varied with MAP in a sigmoid fashion suggestive of pressure autoregulation between 60 and 150 mm Hg (r2 = 0.72). The minimum PbrO2 with hypotension was 1.4 mm Hg, and the maximum PbrO2 with hypertension was 97.2 mm Hg. In addition, CBF correlated linearly with PbrO2 during CO2 reactivity testing (r2 = 0.84). CONCLUSION: In the uninjured brain, PbrO2 exhibits CO2 reactivity and pressure autoregulation. The relationship of PbrO2 with ET-CO2 and MAP appears to be similar to those historically established for CBF with ET-CO2 and MAP. This suggests that, under normal conditions, PbrO2 is strongly influenced by factors that regulate CBF. PMID- 11220383 TI - The effect of streptozotocin-induced diabetes on the release of excitotoxic and other amino acids from the ischemic rat cerebral cortex. AB - OBJECTIVE: Hyperglycemic stroke results in increased neuronal damage, the exact mechanism of which is unknown. Lactic acidosis has been implicated; however, increases in the excitotoxic amino acid glutamate, which correlate with increased neuronal damage, may be the cause for the increased damage seen in hyperglycemic stroke. METHODS: Ten Sprague-Dawley rats were treated with streptozotocin (STZ; 50 mg/kg), and 12 normoglycemic rats were used as controls. Using a four-vessel occlusion model, global ischemia was assessed at 5 to 7 days after treatment in five animals (acute STZ group) or at 4 to 6 weeks after treatment in five animals (chronic STZ group). The cortical cup model was used to collect superfusates under basal, ischemic, and reperfusion conditions and analyzed for nine different amino acids using high-performance liquid chromatography. RESULTS: Plasma glucose levels were significantly higher in the acute and chronic STZ groups as compared with the control group. Plasma lactate levels were higher in the acute STZ group as compared with the control or chronic STZ groups. Extracellular cortical glutamate levels were significantly reduced during reperfusion in the acute STZ group and during ischemia/reperfusion in the chronic STZ group as compared with the controls. Levels of extracellular gamma-aminobutyric acid were significantly reduced in the acute and chronic STZ groups as compared with the controls. CONCLUSION: A chronic state of hyperglycemia results in reduction in extracellular brain glutamate levels during ischemia/reperfusion and therefore does not appear to be responsible for the increased neuronal damage seen in diabetic stroke. Chronic hyperglycemia also causes decreased extracellular gamma aminobutyric acid levels, which, because of the loss of the inhibitory effects of this neurotransmitter, could contribute to the increased damage observed in hyperglycemic stroke. PMID- 11220384 TI - L-buthionine sulfoximine potentiates the antitumor effect of 4 hydroperoxycyclophosphamide when administered locally in a rat glioma model. AB - OBJECTIVE: L-buthionine sulfoximine (BSO) inhibits glutathione synthesis and may modulate tumor resistance to some alkylating agents, but it has not been proven effective in the treatment of intracranial neoplasms. To evaluate this drug for the treatment of brain tumors, we studied the use of BSO for potentiating the antineoplastic effect of 4-hydroxyperoxycyclophosphamide (4-HC) in the rat 9L glioma model. METHODS: The survival of male Fischer 344 rats with intracranial 9L gliomas was measured after implantation of controlled-release polymers containing one of the following: no drug, BSO, 4-HC, or both BSO and 4-HC. The efficacy of intracranial 4-HC treatment was assessed with and without serial systemic intraperitoneal BSO injections. Tissue glutathione levels were measured in the brains, tumors, and livers of animals treated with intraperitoneal injections or local delivery of BSO. RESULTS: The median survival of animals treated with intracranial polymers containing 4-HC was 2.3 times greater than that of controls. This survival benefit was doubled by local delivery of BSO. In contrast, systemic BSO therapy did not improve survival time. In animals that were treated systemically, both liver and tumor glutathione levels were significantly lower than they were in control animals. In the locally treated animals, glutathione levels were reduced in the brain tumor but not in the liver. CONCLUSION: These results demonstrate that local but not systemic delivery of BSO enhances the antineoplastic effect of 4-HC in this rat 9L glioma model. In addition, because local delivery of BSO within the brain did not deplete glutathione levels systemically, this method of treatment may be safer than systemic administration of BSO. PMID- 11220386 TI - The fatal wound of Hector, according to a drawing by Peter Paul Rubens designed for tapestry weaving. AB - According to the Iliad(Chapter XXII, Verses 322-329), Hector, while fighting his last duel, was almost entirely protected by bronze armor, with only a small area "where the clavicle marks the boundary between neck and thorax" exposed. It was precisely into this area, "the shorter way to death," that Achilles thrust his lance. This fatal wound, although covering Hector with blood, allowed the victim to pronounce a few words. In designing the Story of Achilles, his fourth and last series of drawings especially designed for tapestry weaving, Rubens depicted Achilles stabbing Hector near the midline of his neck. There is evidence that Rubens was always well acquainted with the literary sources of his pictures. It is also likely that he became familiar with contemporary editions of the Iliad that were enhanced with commentaries. Realizing that the wound depicted in his original drawing should have prevented Hector from speaking, Rubens altered the scene, then showing the lance piercing the cervical vascular bundle. The careful scrutiny for literary accuracy that was typical of Rubens' artistic behavior did not prevent an additional minor imprecision in the final tapestry. Nevertheless, his outstanding expressive power enabled him to give form to a gigantic baroque representation of the death of Hector in masterly fashion. PMID- 11220385 TI - Elective trepanation for acute epidural hematoma by Dr. Nicolaes Tulp (1593 1674). AB - The improved knowledge of human anatomy in the 16th century led to an increase in the practice of cranial trepanation in clinical cases, and detailed definitions of indications for performing this operation were provided by several authors. It was not until the 18th century, however, that detailed data on patient selection, decision making, and the postoperative course of this surgical procedure became available through individual case reports. In this historical context, a report written in 1641 by the Dutch physician Dr. Nicolaes Tulp is remarkable. This report, one of the first individual commentaries on the surgical treatment of an acute epidural hematoma, has not yet gained international recognition. PMID- 11220387 TI - Historical perspective on the Department of Neurosurgery at the Henry Ford Hospital. AB - The Henry Ford Hospital (HFH) was founded in 1915 as a philanthropic gift from Henry Ford, the automobile magnate and inventor of the Model T. The hospital and its organizational structure represented a nonsectarian facility that would provide care for all members of society. The system was patterned after the newest and most modern medical centers at the time in Europe, Canada, and the United States, including the German Krankenhauser, the Johns Hopkins Hospital, the Mayo Clinic, and the Peter Bent Brigham Hospital in Boston. The HFH grew into the Henry Ford Health System in the 1970s to 1990s, with the acquisition of other hospitals, the development of a multiple-region-based clinic system through southeastern Michigan, and the development of comprehensive, vertically integrated health care systems. The Division of Neurosurgery at HFH was established by Albert Crawford in 1926. The tradition of training residents in neurosurgery began in 1946, and the residency training program was accredited by the American Board of Neurosurgery in 1954. In 1970, the Division of Neurosurgery of the Department of Surgery was combined with the Division of Neurology to create the joint Department of Neurology and Neurosurgery. A separate Department of Neurosurgery was established in 1981. Four individuals have served as chairmen of the Department of Neurosurgery at HFH, i.e., Albert Crawford (1926-1952), Robert Knighton (1952-1978), James Ausman (1978-1991), and Mark Rosenblum (1992 to the present). During the 1980s and 1990s, HFH evolved into the vertically integrated, regionally distributed Henry Ford Health System. Under the current direction of Dr. Rosenblum, the Department of Neurosurgery at HFH has grown to include 11 full-time neurosurgeons, 2 neuro-oncologists, and 3 investigators with Ph.D. degrees and has recently expanded into three additional hospitals in southeastern Michigan, paralleling the growth of the system. The faculty annually treats more than 2,000 cases in all neurosurgical subspecialties, ranging from neuro-oncological surgery, cranial base surgery, radiosurgery, cerebrovascular surgery, epilepsy surgery, treatment of movement disorders, pain and spasticity surgery, pediatric neurosurgery, and neurotrauma treatment to complex instrumentation of the spine. This article chronicles the history of the Henry Ford Health System and the Department of Neurosurgery, its research endeavors, and its residency training program. PMID- 11220388 TI - Primary intradural classic chondrosarcoma: case report and literature review. AB - OBJECTIVE AND IMPORTANCE: The exact origin of rare intradural chondrosarcomas remains obscure. We present a case report of an intradural classic chondrosarcoma (a very rare subtype of chondrosarcoma in this location), with a review of the literature, in an attempt to clarify the histogenesis of these tumors. CLINICAL PRESENTATION: A 48-year-old man presented with a 12-month history of progressive right hemiparesis. Computed tomography and magnetic resonance imaging demonstrated a left parietal space-occupying lesion. INTERVENTION: The patient underwent an image-guided, left parietal parasagittal craniotomy. An extrinsic tumor, which seemed to arise from the dura, was macroscopically removed. There was no bone involvement. The histological examination revealed a Grade II classic chondrosarcoma with tumor infiltration into the dura. Adjuvant radiotherapy was administered. CONCLUSION: Intradural chondrosarcomas are rare tumors, the majority of which are mesenchymal. Classic chondrosarcomas in this location are much rarer. Their histogenesis is uncertain. In this case, the origin seems to be from the dura. Because of the malignant potential of these tumors, radical extirpation whenever possible, followed by radiotherapy, is indicated. PMID- 11220389 TI - Malignant giant-cell tumor of the parietal bone: case report and review of the literature. AB - OBJECTIVE AND IMPORTANCE: Giant-cell tumors (GCTs) are primary bone tumors that involve long bones in 75 to 90% of patients. They seldom develop in the cranium and are very rare in patients older than 60 years of age. A GCT rarely occurs with Paget's disease; when it does, however, it is most commonly associated with the polyostotic form and tends to involve the craniofacial bones. Pagetic GCTs are less aggressive than GCTs that are not associated with Paget's disease. CLINICAL PRESENTATION: We report the case of an 81-year-old woman with a painless left parietal mass and asymptomatic monostotic parietal Paget's disease. INTERVENTION: Surgical resection was performed, and histological examination of the lesion demonstrated Paget's disease with a malignant GCT. An incidental, low grade, small-cell lymphocytic lymphoma also was noted. The patient experienced local recurrence of the malignant GCT and eventually died after developing pulmonary metastases of the malignant GCT. CONCLUSION: This case is the first reported example of a patient with a malignant GCT of the cranium associated with monostotic Paget's disease. It provides evidence that not all pagetic GCTs in the cranium are benign, as has been reported. PMID- 11220390 TI - Congenital reactive myofibroblastic tumor of the petrous bone: case report. AB - OBJECTIVE AND IMPORTANCE: Myofibroblastic tumors are members of a diverse spectrum of neoplastic and quasineoplastic lesions that occur most commonly during childhood and typically involve soft tissues. We present a case of a congenital reactive myofibroblastic tumor of the petrous bone (i.e., cranial fasciitis) that was successfully treated with surgical excision. CLINICAL PRESENTATION: A newborn girl with congenital right facial palsy and deafness was noted during imaging evaluation to have a large enhancing mass that was destroying the right petrous bone and extending into the posterior and middle cranial fossae. INTERVENTION: After embolization, an open biopsy was performed, which revealed a moderately cellular, spindle cell neoplasm without mitosis or necrosis, with scattered lymphocytes, eosinophils, and multinucleated giant cells. The spindle cells demonstrated strong immunoreactivity for vimentin, muscle-specific actin, and alpha-smooth muscle actin, with prominent reticulin staining between individual cells. Staining for CD68, a histiocyte marker, was positive within the multinucleated giant cells and many of the spindle cells; CD34, S-100, and desmin staining was absent. On the basis of these findings, the lesion was classified as a reactive myofibroblastic tumor, consistent with a cranial variant of nodular fasciitis. Because of the large size and significant mass effect of the tumor, a resection was performed several days later, using a combined supra- and infratentorial approach. Dense adherence of the mass to the walls of the sigmoid sinus and the carotid artery precluded complete resection without sacrifice of these vessels, which was not performed because of the known potential of these tumors to remain stable or regress after extensive subtotal resection. The presumed residual tumor subsequently regressed, and the patient has exhibited no detectable residual disease in 2 years of follow-up monitoring. CONCLUSION: Reactive myofibroblastic tumors of the calvarium are uncommon lesions that superficially resemble sarcomas. Recognition of this diagnostic entity is important, to avoid unnecessary treatment with intensive adjuvant therapy. Although the management of these tumors relies predominantly on surgical resection, surgical decision-making should take into account the fact that small areas of residual disease can regress spontaneously. PMID- 11220392 TI - Stereotactic radiosurgery for recurrent central neurocytoma: case report. AB - OBJECTIVE AND IMPORTANCE: Neurocytomas are typically benign tumors that have high local control rates after gross total resection. Nevertheless, tumor recurrence is possible, and some patients have aggressive tumors. CLINICAL PRESENTATION: A 26-year-old woman had a recurrent, asymptomatic neurocytoma 3 years after gross total resection. INTERVENTION: The patient underwent stereotactic radiosurgery for the tumor recurrence. Thirty-four months later, the patient remained neurologically intact, and the tumor had decreased significantly in size. CONCLUSION: Radiosurgery may be a viable treatment option for patients with recurrent neurocytomas or for patients whose tumor resections were subtotal. PMID- 11220391 TI - Reversal of focal misery perfusion after intracranial angioplasty: case report. AB - OBJECTIVE AND IMPORTANCE: The presence of reduced blood flow and increased oxygen extraction fraction (OEF) (misery perfusion) in the hemisphere distal to an occluded carotid artery is a proven risk factor for subsequent stroke. Whether angioplasty of intracranial stenosis is sufficient to reverse this condition has not been documented. CLINICAL PRESENTATION: A 67-year-old man exhibited progressive right hemispheric ischemic symptoms despite maximal antiplatelet and antithrombotic therapy. Angiography demonstrated focal 80% stenosis of the supraclinoid segment of the ipsilateral internal carotid artery. TECHNIQUE: 15O positron emission tomographic measurements of cerebral blood flow and OEF were made before and after transfemoral percutaneous angioplasty. OEF values measured before angioplasty were elevated in the middle cerebral artery distal to the stenosis. Angioplasty reduced the degree of luminal stenosis to 40% (linear diameter). OEF values measured 36 hours after angioplasty were normal. CONCLUSION: Angioplasty of intracranial stenosis can restore normal cerebral blood flow and oxygen extraction, despite mild residual stenosis after the procedure. Hemodynamic measurements may be useful for the identification of patients with the greatest potential to benefit from angioplasty. PMID- 11220394 TI - Preservation of large bridging veins of the cranial base: technical note. AB - OBJECTIVE: Sacrifice of a bridging vein in the cranial base occasionally may cause significant postoperative morbidity. We report a simple method for preserving large bridging veins of the cranial base by reflecting the dura when a subtemporal or transsylvian approach is used. METHODS: In the subtemporal approach, when a larger bridging vein enters the dura attached to the bone of the temporal base before it empties into the dural sinus, the dura is dissected widely from the bone and is cut vertically toward the medial side of the temporal base in front of the entrance of the vein into the dura. The dura, which includes part of the entrance and interdural course of the vein, is reflected and retracted over the brain. In the transsylvian approach, when the bridging segment of the superficial sylvian vein becomes taut because of retraction of the temporal lobe, the dura is incised along the sphenoid ridge and is dissected and freed from the sphenoid bone. RESULTS AND CONCLUSION: This dura-reflecting technique facilitates brain retraction without exerting tension on the bridging vein of the cranial base and is expected to help avoid injury to bridging veins during neurosurgical procedures. PMID- 11220393 TI - Intraoperative reduction of locked facets in the cervical spine by use of a modified interlaminar spreader: technical note. AB - OBJECTIVE: Facet dislocations commonly require intraoperative reduction after closed reduction with traction has failed. Reduction should be performed in a gradual, controlled fashion to prevent additional inadvertent spinal cord compromise. METHODS: We describe a new technique for safe and simple dorsal reduction of facet dislocations by use of a modified interlaminar spreader. This technique requires only minimal controlled manipulation of the spine. RESULTS: We have used this technique in 52 consecutive patients with no complications or failures related to its use in open reduction. This technique increases the stability of the cervical spine after reduction because it limits bone removal from the facet joints. CONCLUSION: This technique provides a feasible and reliable approach to open reduction of cervical facet dislocations via the posterior approach. PMID- 11220395 TI - Temporalis muscle resuspension using titanium miniplates and screws: technical note. AB - OBJECTIVE: To describe the technique for and results of using titanium miniplates and screws for resuspension of the temporalis muscle after osseous detachment during cranial procedures requiring exposure of and access to the frontotemporoparietal region. METHODS: Thirty-four patients, who were being treated with various cranial procedures, underwent resuspension of the dissected temporalis muscle, using 1.5-mm or 1.3-mm titanium plates and screws, after bone flap replacement. RESULTS: The temporalis muscle was successfully and securely resuspended in all cases, using the plates and screws. There were no infections, muscle tears, dislodgement, fractures, or temporal hollowing in any of the cases. In four cases that required re-exploration, the muscle was observed to be rigidly fixated and scarred to the bone. CONCLUSION: The use of titanium plates and screws is a safe, simple, successful alternative for reattachment of temporalis muscles for patients undergoing cranial procedures. PMID- 11220396 TI - Effects of radiation on cerebral vasculature: a review. PMID- 11220397 TI - Cerebral infarction after neuroendoscopic third ventriculostomy: case report. PMID- 11220398 TI - Limits of intermittent jugular bulb oxygen saturation monitoring in the management of severe head trauma patients. PMID- 11220399 TI - Advanced surgical approach for selective amygdalohippocampectomy through neuronavigation. PMID- 11220400 TI - Program requirements for residency/fellowship education in neuroendovascular surgery/interventional neuroradiology: special report on graduate medical education. PMID- 11220401 TI - Methylmethacrylate insufficiently fixes deep brain stimulator lead position. PMID- 11220402 TI - Vitamin K in neonates: how to administer, when and to whom. AB - Vitamin K-dependent factors are lower in neonates than in adults, and these anomalies are more prevalent in preterm neonates and in breast-fed infants. Vitamin K deficiency can account for vitamin K deficiency bleeding (VKDB) which occurs in 3 forms--early, classic and late. Vitamin K should be administered to all neonates at birth or immediately afterwards. However, the protocols for administration (route of administration, dosage, number of doses) remain a subject of discussion. Oral administration of a single dose of vitamin K protects against classical and early VKDB, but is less effective than intramuscular (IM) prophylaxis for the prevention of late VKDB. Although an increased risk of solid tumour, associated vitamin K administration, can be definitively excluded, a low potential risk of lymphoblastic leukaemia in childhood can not be ruled out. For formula-fed neonates without risk of haemorrhage, a 2 mg oral dose of vitamin K at birth, followed by a second 2 mg oral dose between day 2 and 7, is probably sufficient to prevent VKDB. For infants who are exclusively or nearly exclusively breast-fed, weekly oral administration of 2mg (or 25 microg/day) vitamin K after the initial 2 oral doses is justified at completion of breast-feeding. For neonates at high risk of haemorrhage (premature, neonatal disease, birth asphyxia, difficult delivery, any illness which will delay feeding, known hepatic disease, maternal drugs inhibiting vitamin K activity), the first dose must be administered by the IM or slow intravenous route. Doses should be repeated, particularly in premature infants, by a route of administration decided for each dose according to the clinical state of the infant. For infants of mothers treated with drugs inhibiting vitamin K activity, antenatal maternal prophylaxis (10 to 20 mg/day orally for 15 to 30 days before delivery) prevents early VKDB. After neonatal prophylaxis, as for infants at high risk of haemorrhage, doses need to be repeated at a rate and route of administration decided for each dose, according to the clotting factor profile specific for each infant. PMID- 11220403 TI - The ethics of drug research in children. AB - The obligation of society to improve the welfare of its members requires the conduct of paediatric drug trials. Nevertheless, research activities must satisfy obligations to individual participants. The obligation to protect the welfare of children requires that nontherapeutic research procedures generally involve no more than minimal risk. It also requires that randomisation occurs only when the relative merits of therapeutic procedures remain unsettled among the relevant community of experts. The duty to respect the developing autonomy of children requires that they be included in decision-making about research participation in a manner consistent with the level of their decision-making capacity. However, when children lack mature decision-making capacities, the duty of parents to protect their welfare may properly constrain their choices. Justice requires that the benefits and burdens of research be distributed in a manner that assures equal opportunity for all children. Vulnerable children should receive special protection against the burdens of nontherapeutic research procedures. The benefits of participating in clinical trials should be available to all children with serious illnesses for which current treatment is unsatisfactory. Justice also requires that initiatives be undertaken to rectify current shortcomings in the scope of paediatric drug research. Striking an appropriate balance between obligations to conduct research and to protect the interests of participants is essential to the moral integrity of paediatric drug research. PMID- 11220405 TI - Caffeine citrate: a review of its use in apnoea of prematurity. AB - Apnoea of prematurity is a common condition in neonates born at less than 37 weeks' gestational age; it affects approximately 90% of premature neonates weighing under 1000 g at birth, and 25% of infants with a birthweight of less than 2500 g. Caffeine, a methylxanthine which occurs naturally in many plants, has been used for over 20 years to treat apnoea of prematurity. In a recent double-blind, placebo-controlled trial, apnoea was eliminated or reduced by at least 50% in significantly more neonates receiving caffeine citrate as first-line treatment than those receiving placebo. In a nonblind trial, caffeine citrate was more effective at reducing apnoeic episodes when compared with neonates receiving no treatment. Caffeine as first-line treatment demonstrated similar efficacy to theophylline or aminophylline (theophylline ethylenediamine) in 4 small randomised studies. Caffeine citrate was generally well tolerated in short term clinical trials, with very few adverse events reported. Caffeine was associated with fewer adverse events than theophylline in randomised trials. No differences in the incidence of individual adverse events were reported between caffeine citrate and placebo in a double-blind, randomised trial. Long term tolerability data are not yet available. CONCLUSIONS: Caffeine citrate was generally well tolerated by neonates in clinical trials and it decreased the incidence of apnoea of prematurity compared with placebo. It has demonstrated similar efficacy to theophylline, but is generally better tolerated and has a wider therapeutic index. Caffeine citrate should, therefore, be considered the drug of choice when pharmacological treatment of apnoea of prematurity is required. PMID- 11220404 TI - Immunosuppressive drugs in paediatric liver transplantation. AB - Orthotopic liver transplantation is established treatment for children with acute and chronic liver failure. Despite advances in pre- and postoperative management, innovative surgical techniques and new immunosuppressive drugs, acute and chronic rejection remains a problem. In addition, well established adverse effects of commonly used immunosuppressive drugs are no longer accept able. More potent, but less toxic, immunosuppressive agents have been developed and some novel compounds are now entering routine practice. Cyclosporin was the cornerstone of immunosuppressive therapy until the introduction of its novel pharmaceutical form (Neoral) with improved bioavailability, lower inter- and intraindividual pharmacokinetic variability and improved graft survival. Recently, tacrolimus, a macrolide drug with a similar mode of action, but much higher potency, was introduced and, at present, is the only agent which can successfully replace cyclosporin as a first-line immunosuppressive drug. Mycophenolate mofetil has recently been approved for use in adult and paediatric renal transplant recipients. It has a similar mode of action to cyclosporin and tacrolimus, but acts at a later stage of the T cell activation pathway. Administration with standard immunosuppressive drugs reduces the incidence of acute rejection and enables cyclosporin and tacrolimus dose reduction, thus reducing the risk of associated toxic effects. Phase I and II trials with sirolimus (rapamycin), a macrolide antibiotic, have shown comparable immunosuppressive action, when administered in conjunction with standard immunosuppressants. Further clinical trials need to be carried out to establish efficacy, tolerability and pharmacokinetics in paediatric transplant recipients. Monoclonal antibody therapy (daclizumab and basiliximab) is an exciting new development whereby T cell proliferation is inhibited by selective blockade of interleukin (IL)-2 receptors. Preliminary results, when used in combination with a standard immunosuppressive regimen, are good with respect to incidence of acute graft rejection, host immune response and adverse effects. FTY720 is a novel synthetic immunosuppressive compound which induces a reduction in peripheral blood lymphocyte count through apoptotic T cell death or accelerated trafficking of T cells into lymphatic tissues. Experimental animal studies demonstrated synergistic action in combination with low dose cyclosporin or tacrolimus, potentiating their immunosuppressive effects. Further studies are being carried out to determine its potential for application in organ transplantation. Despite this rapid development of novel compounds, it will take many years before they may become part of standard protocols in paediatric transplantation medicine. Further development and research of efficacy and tolerability of existing drugs is, therefore, vital. PMID- 11220407 TI - Introduction: infections in the intensive care unit. PMID- 11220406 TI - Management of sepsis and septic shock in infants and children. AB - Sepsis and septic shock constitute an important cause of morbidity and mortality in critically ill children. Thus, the systemic response to infection and its management remains a major challenge in clinical medicine. Apart from antibiotic administration, the majority of available therapies are limited to supportive strategies, although considerable efforts are being undertaken to devise innovative approaches that modulate host inflammatory responses. In suspected sepsis, 2 or 3 days' empiric antibiotic therapy should begin immediately after cultures have been obtained without awaiting results. Antibiotics should be re evaluated when the results of the cultures and susceptibility tests are available. The initial antibiotic (combination) is determined by the likely causative agent, susceptibility patterns within a specific institution, CNS penetration, toxicity, and the patient's hepatic and renal function. The likely offending micro-organism in turn depends primarily on the patient's age, coexistence of any premorbid condition leading to impaired immune response, and the presenting signs and symptoms. Close attention to cardiovascular, respiratory, fluid and electrolyte, haematological, renal and metabolic/nutritional support is essential to optimise outcome. Fluid resuscitation is of utmost importance to overcome hypovolaemia on the basis of a diffuse capillary leak. Monitoring and normalisation of the heart rate is essential. In case of nonresponse to fluid resuscitation, inotropic and vasoactive agents are commonly used to increase cardiac output, maintain adequate blood pressure and enhance oxygen delivery to the tissue. Because respiratory distress syndrome is seen in about 40% of critically ill children with septic shock, increased inspired oxygen is essential. To provide optimal relief from respiratory muscle fatigue and facilitate the provision of positive airway pressure, early intubation and mechanical ventilation should be considered. Renal support is essential to avoid prolonged renal shutdown in hypoperfusion states. Haematological support comprises replacement therapy of clotting factors to overcome disseminated intravascular coagulation. Metabolic support may include glucose support, extraction of ammonia from the body and recognition of liver dysfunction. Nutritional support may modify the inflammatory host response, and early enteral feeding can improve outcome in critical illness. To date, glucocorticoid and non-glucocorticoid anti-inflammatory agents have not shown significant benefit in septic patients. PMID- 11220408 TI - Intravascular catheter-related infections: a preventable challenge in the critically ill. AB - In modem medicine, central venous catheters (CVCs) have a pivotal role in the management of critically ill patients. The most serious complication of effective CVC placement is catheter-related bloodstream infection (CRBSI). Microbial colonization and CRBSI are the byproducts of the interaction of 4 factors: (1) microbial factors (hydrophobicity and exopolysaccharide production), (2) host factors (such protein adhesins as fibrin and fibronectin that attach to the catheter surface), (3) catheter material (hydrophobicity, surface charges, thrombogenicity), and (4) iatrogenic factors (total parenteral nutrition, interleukin-2). The organisms most frequently associated with CRBSI are Staphylococcus epidermidis, Staphylococcus aureus, and Candida spp. CRBSIs were traditionally diagnosed through semiquantitative or quantitative cultures of the catheter tip. However, the diagnosis can be achieved without catheter removal through cultures of blood specimens collected simultaneously though the CVC and a peripheral vein. Currently, the most effective method of preventing a CRBSI is the use of a CVC coated with antimicrobial agents. Intravenous administration of vancomycin for 7 days is adequate for an uncomplicated CRBSI caused by coagulase negative staphylococci, and at least 10 days of therapy with beta-lactams is required for an uncomplicated infection caused by methicillin-sensitive S. aureus. CRBSI caused by Candida albicans or Candida parapsilosis can be treated with at least 14 days of therapy with fluconazole or amphotericin B. In the case of Candida krusei, only amphotericin B is effective. PMID- 11220409 TI - Ventilator-associated pneumonia: incidence, risk factors, and microbiology. AB - Ventilator-associated pneumonia (VAP) is a pulmonary infection that occurs after at least 48 hours of mechanical ventilation (MV). The incidence depends on several factors, although the most important are those related to the host and duration of MV. VAP can be differentiated into early-onset (<5 days) and late onset types (> or =5 days). The overall incidence of VAP varies between 9% and 70% (average, 20% to 25%), and the majority of episodes occur within the first 5 days. Risk factors for VAP include prolonged MV, older age, supine body position, and type of comorbidity. Oropharyngeal colonization appears to be a risk factor for early-onset pneumonia, whereas prolonged MV and antibiotic pretreatment, especially with broad-spectrum drugs, increase the risk for late-onset VAP Microaspiration of colonized oropharyngeal secretions is a major cause of early onset VAP, most frequently caused by community-type pathogens. After 5 days of MV, pathological colonization with gram-negative bacteria may occur, and late onset VAP is more likely to be attributable to this group of microorganism. Incidence, risk factors, and microbiology depend strongly on the time frame in which the episode develops. However, initial and pathological colonization during the intensive care unit stay can modify this concept. PMID- 11220410 TI - Trauma, head injury, and neurosurgery infections. AB - Patients with multiple trauma and head injuries are high-risk populations for developing nosocomial infections, which are the first cause of death after 3 weeks of admission. Pneumonia caused by methicillin-sensitive Staphylococcus aureus is the most frequent infection in patients with a decreased level of consciousness. Nevertheless, after 7 days of ventilation, Pseudomonas aeruginosa is the most frequently isolated microorganism in ventilator-associated pneumonia. Central nervous system infections represent only 4% of those experienced by trauma patients; however, if cerebrospinal fluid (CSF) leakage exists, the incidence increases to 50%. The diagnosis of meningitis is difficult because CSF biochemical data are not specific. Patients with spinal cord injuries are at greater risk for developing infections caused by multiresistant microorganisms because of their prolonged hospital stay. PMID- 11220411 TI - Problem pathogens (Pseudomonas aeruginosa and Acinetobacter). AB - A number of factors have been suspected of or identified as increasing the risk for pneumonia or colonization of the lower respiratory tract by Pseudomonas and/or Acinetobacter spp. in the intensive care unit (ICU), including advanced age, chronic lung disease, immunosuppression, surgery, use of antimicrobial agents, presence of such invasive devices as endotracheal and gastric tubes, and type of respiratory equipment. However, there is little doubt that of all these factors, extended ICU care because of severe underlying disease, prolonged respiratory therapy with mechanical ventilation, and prior antimicrobial therapy are the most important. Because the only factor amenable to prevention in this setting is antimicrobial therapy, avoiding unnecessary antibiotics should be a high priority in the management of such patients. Crude mortality rates of 30% to 75% have been reported for nosocomial pneumonia caused by Pseudomonas and/or Acinetobacter spp., with the highest rates reported in ventilator-dependent patients. It is therefore clear that the prognosis associated with this type of infection is considerably worse than that associated with infection caused by other gram-negative or gram-positive bacteria. Because bactericidal synergy against Pseudomonas and Acinetobacter spp. has been shown when carbenicillin and an aminoglycoside are combined, the use of an effective beta-lactam (piperacillin, ticarcillin, ceftazidime, or imipenem) and aminoglycoside combination remains the preferred therapeutic approach when possible. Future research efforts should also aim to improve our ability to diagnose and exclude infection in the ICU setting to avoid administering unnecessary antibiotics to patients without true pulmonary infection. PMID- 11220412 TI - Extended-spectrum beta-lactamases. AB - Resistance to broad-spectrum cephalosporins among Klebsiella pneumoniae has increased significantly, particularly in the intensive care unit setting, in the past decade. The problem has been noted not only in the United States, but around the world. A major mechanism responsible for this is the emergence of extended spectrum beta-lactamases (ESBLs). These plasmid-mediated beta-lactamases confer resistance to broad-spectrum beta-lactam antibiotics, including third- and fourth generation cephalosporins, aztreonam, and extended-spectrum penicillins. Other resistances, such as aminoglycoside and trimethoprim-sulfamethoxazole resistance, are often cotransferred on the same plasmid. Fluoroquinolone resistance is also frequently associated, resulting in an organism resistant to most broad-spectrum options. The carbapenems are currently considered the drug of choice for these pathogens. Prevention and control measures are important because of the multiresistant nature of these pathogens. Such traditional infection control measures as contact precautions are recommended. In addition, because this type of antimicrobial resistance appears to be particularly influenced by antibiotic use, antibiotic control measures may also be a very important intervention in controlling the spread of ESBLs. PMID- 11220413 TI - Staphylococcal infections in the intensive care unit. AB - Staphylococcus aureus and coagulase-negative staphylococci are among the most common causes of nosocomial infections in the intensive care unit (ICU). The clinical presentation of staphylococcal device-related infections, pneumonias, or surgical wound infections is not unique. However, treatment of these infections is increasingly problematic because of the resistance of clinical isolates to a widening number of antimicrobial agents. The confluence of critically ill patients and the need for multiple invasive procedures, as well as the use of broad-spectrum antimicrobial agents in the ICU, set the stage for the emergence of these multidrug-resistant staphylococci. In the past 10 years, there has been a progressive increase in the overall resistance of staphylococci to antimicrobial agents. Conventional infection control measures, such as handwashing and isolation precautions, to prevent the spread of staphylococcal infections in the ICU setting remain of critical importance. New approaches, including the prophylactic use of topical antistaphylococcal agents to eliminate nasal colonization in high-risk ICU patients and the development of antistaphylococcal vaccines, are currently being investigated. PMID- 11220414 TI - Vancomycin-resistant enterococci. AB - Over the last 2 decades, enterococci, formerly viewed as organisms of minimal clinical impact, have emerged as important hospital-acquired pathogens in immunosuppressed patients and intensive care units (ICUs). Vancomycin resistance in enterococci is increasing steadily. Vancomycin-resistant enterococci (VRE) composed 26% of nosocomial enterococci in 1999, a 47% increase from 1994 to 1998. More that 25% of ICU enterococci are resistant to vancomycin. Antimicrobial therapy is problematic for all VRE, but particularly when bactericidal activity is necessary. Quinipristin-dalfopristin and linezolid are 2 new approved antimicrobials for the treatment of recalcitrant infections caused byVRE. Control of the transmission of VRE, although successful in preventing infections, is neither simple nor inexpensive, and VRE has become endemic in many hospitals. However, endemicity poses serious risks to the health of current and future patients, and of itself, is expensive. Data on the cost-effectiveness of VRE prevention programs are currently lacking and urgently needed; however, because the added cost of a single VRE infection far exceeds those of gowns, gloves, and screening, it seems likely that such control programs represent significant cost savings for those hospitals willing to undertake them. PMID- 11220415 TI - Infection control in intensive care units and prevention of ventilator-associated pneumonia. AB - Ventilator-associated pneumonia (VAP) is considered the most frequent infection in the intensive care unit (ICU), although incidence rates depend on the diagnostic methods. Because VAP has been associated with increased mortality and greater costs for medical care, prevention remains an important goal for intensive care medicine. Selective digestive decontamination (SDD), the most frequently studied method of infection prevention, is still controversial despite more than 30 prospective randomized trials and 6 metaanalyses. SDD reduces the incidence of VAP diagnoses, but beneficial effects on duration of ventilation or ICU stay, antibiotic use, and patient survival have not been shown unequivocally. Although recent metaanalyses suggest a 20% to 40% decrease in ICU mortality for SDD used with systemic prophylaxis, this benefit should be confirmed in a large, prospective, randomized study, preferably with a cost-benefit analysis. Selection of pathogens resistant to the antibiotics used in SDD remains the most important drawback of SDD, rendering SDD contraindicated in wards with endemic resistant problems. Other methods of infection prevention that do not create a selective growth advantage for resistant microorganisms may be more useful. Among these are the use of endotracheal tubes with the possibility of continuous aspiration of subglottic secretions, oropharyngeal decontamination with antiseptics, or the semirecumbent treatment position of patients. Although these methods were successful in single studies, more data are needed. Notwithstanding the potential benefits of these interventions, such classic infection control measures as handwashing remain the cornerstone of infection prevention. PMID- 11220416 TI - Diagnostic case study: radiographic findings in pulmonary blastomycosis. PMID- 11220417 TI - Pre-emptive analgesia: importance of timing. PMID- 11220418 TI - Why should we teach medical students? PMID- 11220419 TI - Gastric air tonometry during laparoscopic cholecystectomy: a comparison of two PaCO2 levels. AB - PURPOSE: Pneumoperitoneum can cause disturbances in acid-base balance and splanchnic perfusion. We studied the effect of ventilation on acid-base balance and gastric mucosal tonometric values in patients undergoing laparoscopic cholecystectomy. METHODS: Twenty-four patients (ASA I-II) were randomly allocated into two groups. In the fixed ventilation group, ventilation was constant allowing free increase in PCO2, while in the constant CO2 group end-tidal PCO2 was fixed with ventilatory adjustment. Intraabdominal pressure was limited to 12 mmHg. Arterial acid-base balance, automated air tonometric variables and gastric mucosal to arterial PCO2 gap were determined frequently from anesthesia induction until three hours postoperatively. RESULTS: During pneumoperitoneum, in the fixed ventilation group arterial PCO2 changed from 5.0 +/- 0.2 to 6.6 +/- 0.4 kPa and pH from 7.43 +/- 0.03 to 7.33 +/- 0.04, tonometric PCO2 from 5.1 +/- 0.5 to 6.9 +/- 0.4 and pH from 7.44 +/- 0.04 to 7.33 +/- 0.04. In the constant CO2 group these variables remained at control levels (P < 0.01 between groups). The PCO2 gap remained unchanged without any differences between the groups. In the recovery room all measured variables were within normal range in both groups. CONCLUSION: Despite inter-group differences in arterial and tonometric PCO2 and pH values during CO2 pneumoperitoneum, the patients did not develop splanchnic hypoperfusion detectable by air tonometric method, as indicated by normal PCO2 gap in both groups throughout the study. PMID- 11220420 TI - Impact of the initial doses of rocuronium and pancuronium on subsequent maintenance for neuromuscular block. AB - PURPOSE: To determine the impact of the neuromuscular blocking agent given for intubation on the duration of effect of multiple maintenance doses of pancuronium and rocuronium. METHODS: Seventy-eight subjects were randomly assigned to receive one of four dosing combinations for intubation and neuromuscular maintenance: rocuronium for intubation and maintenance, rocuronium for intubation and pancuronium for maintenance, pancuronium for intubation and rocuronium for maintenance, or pancuronium for both. Each time that the first twitch response returned to 25% of the baseline value, the duration of the dose was determined and another maintenance dose was administered. The duration of action of the maintenance doses was compared between the groups. RESULTS: Twitch suppression from the first maintenance dose was shorter for subjects who received rocuronium for both doses (Group RR) compared with that for subjects that received pancuronium (Groups PR & PP) as their intubation dose (17.6 vs 34 & 59.8 min, respectively, P < 0.05). Subjects who received rocuronium followed by pancuronium (Group RP) showed a shorter duration of twitch suppression after the first maintenance dose than the group that received pancuronium for both doses (Group PP) (21.3 vs 59.8 min, P < 0.05). By the third maintenance dose, the influence of the intubating dose on the maintenance dose duration had essentially diminished. CONCLUSIONS: For combinations of rocuronium and pancuronium, the duration of twitch suppression after a maintenance dose is only dependent on the first agent given for the first two maintenance doses administered. PMID- 11220421 TI - High concentrations of isoflurane do not block the sympathetic nervous system activation from desflurane. AB - PURPOSE: The volatile anesthetic desflurane has been associated with neurocirculatory responses that have been relatively refractory to adjuvant treatment. We have employed desflurane to evaluate the integrity of the sympathetic nerve recording after establishment of the anesthetized state with another anesthetic agent. This retrospective evaluation of data from volunteers determined if higher concentrations of isoflurane that were sufficient to block the neurocirculatory response to laryngeal and tracheal stimulation would abolish the neurocirculatory response to desflurane. METHODS: Data from eight, healthy, young volunteers met our criteria for inclusion. They had been anesthetized with propofol or thiopental and intubated after neuromuscular blockade. Each subject was monitored with radial artery blood pressure (BP), heart rate (HR)(ECG), and sympathetic microneurography. Isoflurane had been administered to achieve a steady state concentration of 1.5 MAC (minimum alveolar concentration) while oxygenation and carbon dioxide were monitored with pulse oximetry and infrared spectrometry, respectively. A deep level of anesthesia was confirmed when laryngoscopy and endotracheal tube movement failed to elicit a neurocirculatory response. A brief exposure to 11% desflurane in the inspired gas was then provided. RESULTS: The responses to desflurane included significant increases in HR, range 32-84 b/min, and BP, range 15-72 mm Hg (P < 0.05). Sympathetic nerve activity increased substantially in the three volunteers with functional nerve recordings. CONCLUSION: In healthy volunteers receiving 1.5 MAC isoflurane, which was sufficient to block the neurocirculatory response to laryngoscopy and tracheal stimulation, there were striking increases in sympathetic outflow, HR and BP when 11% desflurane was substituted for isoflurane. PMID- 11220422 TI - Medication errors in anesthetic practice: a survey of 687 practitioners. AB - PURPOSE: The objectives of this study were to determine: 1) if anesthesiologists had experienced a medication error and 2) to identify causal factors. The perceived value of a Canadian reporting agency for medication errors and improved standards for labels on drug ampoules was also investigated. METHODS: A self reporting survey was mailed to members of the Canadian Anesthesiologists' Society (n = 2,266). Respondents provided free-text descriptions of medication errors and answered fixed response questions. RESULTS: Surveys from 687 anesthesiologists (30% response rate) revealed that 85% of the participants had experienced at least one drug error or "near miss". Although most errors (1,038) were of minor consequence (98%), four deaths were reported. The commonest error involved the administration of muscle relaxants instead of a reversal agent. "Syringe swaps" (70.4%) and the misidentification of the label (46.8%) were common contributing factors. Anesthesiologists (97.9%) reported that they read the ampoule label "most of the time" although the label colour was an important secondary cue. Approximately half of the participants would report the error if a reporting program existed and 84% agreed that improved standards for drug labels would reduce the incidence of error. CONCLUSIONS: Most anesthesiologists experienced at least one drug error. The commonest error was a "syringe swap" that involved a muscle relaxant. Most errors were of minor consequence, however, serious morbidity and mortality resulted from clearly preventable events. These results support the development of improved standards for drug labels and the establishment of a Canadian reporting program for medication errors. PMID- 11220423 TI - The role of anesthesiologists in Canadian undergraduate medical education. AB - PURPOSE: To examine the current role of anesthesiologists in Canadian undergraduate medical education (UME). METHODS: A 93-item questionnaire was mailed to the undergraduate course chairs/coordinators for anesthesia at the 16 medical schools in Canada. RESULTS: Of the faculty anesthesiologists in Canada, 1.7%, 4.9%, and 4.9% teach pre-clerkship lectures, seminars, and PBL tutorials, respectively. Annually, anesthesiologists teach an average of 3.3 hr (range: 0 to 15) of pre-clerkship lectures and 12.8 hr (range: 0 to 48) of pre-clerkship seminars at each medical school. The topics most commonly taught by anesthesiologists in pre-clerkship lectures and seminars are pharmacology and perioperative patient assessment, respectively. An anesthesia rotation during clerkship is mandatory at 13 schools, with an average duration of 9.6 dy (range: 5-20 dy). Clerkship teaching methods vary: ten schools provide seminars, eight use videos, six use computers, six use an airway skills laboratory, and four use an anesthesia simulator. The most common topics taught in clerkship anesthesia seminars are airway management and fluid therapy. CONCLUSION: A very small proportion of faculty anesthesiologists participate in Canadian UME at the pre clerkship level. Considerable variation exists in the amount and format of teaching by anesthesiologists among the Canadian undergraduate curricula, particularly at the pre-clerkship level. However, our results indicate that anesthesiologists are assuming a more important teaching role during clerkship. Our findings may suggest that Canadian medical schools are overlooking the advantages that anesthesiologists offer to UME at the pre-clerkship level, or that many anesthesiologists are reluctant to assume pre-clerkship teaching responsibilities. PMID- 11220424 TI - Patient satisfaction with anesthesia services. AB - PURPOSE: The evaluation of services by patients is an essential component of continuous quality improvement in anesthesiology. Little is known, however, about how to achieve this objective. Our goal was to conduct a systematic review of all available studies on patient satisfaction with anesthesia services, thereby ascertaining the present level of knowledge in this field and suggesting ways of improving current measurement methodologies. SOURCE: We reviewed relevant major data banks--Medline, Dissertation Abstract, Psyclit and Cochrane--between 1980 and 2000 and bibliographies from primary sources. We used the following keywords for our search: quality improvement, anesthesia, quality, patient perceptions, consumer satisfaction, continuous quality improvement, outcome measures. PRINCIPAL FINDINGS: The review yielded 14 pertinent studies. Studies were divided into two groups (A & B), according to the quality of the psychometric evaluation (tests performed to verify the reliability and validity of an instrument). While all studies reported high levels of patient satisfaction with anesthesia services, many used methods of questionable value. None of the 14 studies controlled for any confounding variables, such as social desirability. Four studies had seriously biased their data collection and the majority of the studies lacked rigour in the development of the instrument used to measure patient satisfaction. Only one study presented a definition of the concept measured, and none provided a conceptual model of patients' satisfaction with anesthesia services. CONCLUSION: The currently available studies of patient satisfaction are of questionable value. Only rigorous methods and reliable instruments will yield valid and clinically relevant findings of this important issue in anesthesiology. PMID- 11220425 TI - Timing of pre-emptive tenoxicam is important for postoperative analgesia. AB - PURPOSE: In this prospective randomized study, a comparison was made between the efficacy of 20 mg tenoxicam, administered either, 30 min preoperatively or at induction of anesthesia, for the relief of postoperative pain in patients undergoing ambulatory breast biopsy. METHODS: Seventy-three patients were recruited and all received a standard anesthetic consisting of induction with 2 mg x kg(-1) propofol followed by 5 microg x kg(-1) alfentanyl. No premedication was administered and at the end of the procedure the wounds were infiltrated with 10 ml of bupivacaine (0.5%). Patients were randomized to receive 20 mg tenoxicam intraveneously either 30 min before surgery or at induction of anesthesia. RESULTS: Demographic criteria were similar in both groups. There were differences in pain scores at 30, 60, 120 and 240 min postoperatively (VAS at 30 min 3.2 +/- 1.2 vs 5.5 +/- 1.8; P < 0.001: VAS at 60 min 1.8 +/- 1.2 vs 3.7 +/- 1.9; P < 0.001: VAS at 120 min 0.9 +/- 0.9 vs 1.7 +/- 1.0; P = 0.003: VAS at 240 min 0.5 +/- 0.5 vs 1.1 +/- 0.8; P < 0.001: Expressed as mean +/- SD). There was a difference in the number of patients requiring additional analgesia, in the first four hours postoperatively (12 (33%) vs 27 (73%); P = 0.001) and a difference in the time to additional analgesia in these patients (87.5 +/- 32.5 vs 55.0 +/- 26.8 min; P = 0.002). CONCLUSION: Early administration of pre-emptive tenoxicam 30 min before induction of anesthesia improves postoperative analgesia in patients undergoing ambulatory breast biopsy. PMID- 11220427 TI - Patient-controlled intravenous analgesia using remifentanil in the parturient. AB - PURPOSE: To show the use of the short acting opioid remifentanil for labour analgesia when epidural analgesia is considered to be contraindicated. CLINICAL FEATURES: After Ethics Committee approval and informed consent, six patients (36 40 wk gestation), in whom epidural analgesia was considered contraindicated (women refusing regional analgesia, presenting with coagulation or platelet abnormalities or sepsis) benefited from patient-controlled intravenous analgesia (PCIA) with remifentanil. The Abbott Lifecare patient-controlled analgesia (PCA) pump with remifentanil 50 microg x ml(-1) was set to deliver remifentanil continuous background infusion of 0.05 microg x kg(-1) x min(-1) and 25 microg boluses with a five minutes lockout period. The PCIA was started when the parturients experienced regular painful contractions (cervical dilatation of at least 4 cm) and stopped just before delivery (cervix fully dilated). Maternal monitoring included non-invasive blood pressure measurements, heart rate, percutaneous arterial oxyhemoglobin saturation and respiratory rate. Percutaneous fetal heart rate was continuously monitored. All patients remained alert or sleepy but easily arousable and were satisfied with their analgesia. No particular side effects have been noticed. Apgar scores were between 6 and 10. CONCLUSION: Remifentanil PCIA combining low continuous background infusion and small bolus doses is an alternative when epidural analgesia in labour is contraindicated. Under careful anesthesia monitoring, the technique seems to be safe for both mother and baby, at least when delivery occurs at or near the normal term of pregnancy. PMID- 11220426 TI - Dextromethorphan attenuation of postoperative pain and primary and secondary thermal hyperalgesia. AB - PURPOSE: To determine the effect of 90 mg dextromethorphan (DM) p.o. vs placebo 90 min preoperatively, on the immediate and delayed postoperative course. METHODS: Thirty patients undergoing laparoscopic cholecystectomy or inguinal hernioplasty under general anesthesia were studied. Half (DM) received 90 mg dextromethorphan and half received placebo 90 min before anesthesia. Intravenous Patient Controlled Aanalgesia with morphine was available for two hours within a six-hour observation period; 75 mg diclofenac i.m. prn was given later in PACU and on-ward (24 hr). Pain was assessed using the visual analogue scales. Thermal thresholds for cold and hot sensation and for pain (by limit method) were evaluated at the site of skin incision (primary-) and distantly (secondary hyperalgesia). Von Frey filaments were applied testing touch sensation. Sedation level and morphine consumption were also assessed in PACU. RESULTS: Demographic, surgical and perioperative parameters were similar; no untoward effects were encountered. Pain intensity and sedation were lower, and the feeling of well being was greater, in the DM patients: one vs five (median), two vs five, five vs two, respectively, P <0.01 (90 min time-point). Thermal application revealed absence of primary and secondary hyperalgesia only in the DM patients; von Frey filaments induced similar pain sensation in both groups. Mean morphine/group, morphine/weight and diclofenac injection rates were approximately 55% lower in the DM group: 2.1 +/- 1.2 (SD) vs 4.7 +/- 2.3, 0.03 +/- 0.02 vs 0.07 +/- 0.03, 1.0 +/- 0.3 vs 2.4 +/- 0.2, respectively, P <0.01. CONCLUSIONS: Compared with placebo, DM enabled reduction of postoperative analgesics consumption, improved well-being, and reduced sedation, pain intensity and primary and secondary thermal hyperalgesia. PMID- 11220428 TI - Bilateral paravertebral block: a satisfactory alternative for labour analgesia. AB - PURPOSE: To describe a new technique of paravertebral block for labour analgesia and to report the successful use of bilateral paravertebral block in four parturients with contraindications to conventional labour epidural analgesia. CLINICAL FEATURES: Four parturients with contraindications to lumbar epidural analgesia, who were seen either in consultation prenatally or after requesting analgesia when in labour, consented to paravertebral blocks for the management of first stage of labour pain. Bilateral paravertebral blocks were performed at T10 L1 level, initially blocking all four levels with 4 ml bupivacaine 0.5% with epinephrine 1:200000 and then reducing the number of levels blocked to two and finally one. With the entry point 2 cm lateral to the inferior edge of the T11 spinous process, a 22G spinal needle was advanced perpendicular to all planes until contact was made with the transverse/superior articular process of T12, at a depth of 3-5 cm. The needle was then walked superiorly (T11) and inferiorly (T12 nerve root) off the transverse/articular process and advanced 1.5 cm into the paravertebral space. All four patients had relief of pain such that they were "comfortable" and able to cope with labour although they continued to experience deep pelvic and rectal pain. The patients tolerated the initiation of the blocks well, remained hemodynamically stable, and did not suffer any adverse effects. CONCLUSION: Bilateral paravertebral block provides adequate analgesia for the first stage of labour and could be an alternative analgesic technique for some parturients with contraindications to conventional labour epidurals. PMID- 11220430 TI - Oral transmucosal midazolam premedication for preschool children. AB - PURPOSE: To evaluate the acceptance and effectiveness of 0.2 mg x kg(-1) of oral transmucosal midazolam as a premedicant in infants and preschool children. METHOD: In a randomized, prospective double-blind placebo controlled study, 44 healthy children, between the ages of eight months to six years, presenting for elective surgery were divided in two groups. The medicated group received 0.2 mg x kg(-1) of injectable midazolam mixed with an equal volume of strawberry syrup and the placebo group received plain syrup 0.08 ml x kg(-1). Medications were placed on the anterosuperior aspect of the child's tongue in 3-5 aliquots of 0.2 0.4 ml. A blinded observer assessed the acceptance of the medication by willingness to open the mouth for the next aliquot and the efficacy of the medication was assessed by ease of separation from the parent. RESULTS: Ninety six percent of the children in the placebo group and 95% in the midazolam group willingly accepted the medication. Separation of children from parents was successful in 95% of the medicated children compared with 59% in the placebo group (P = 0.006). CONCLUSION: Oral midazolam in thick strawberry syrup, administered in small aliquots via the oral transmucosal route was well accepted and proved to be an effective premedicant in infants and preschool children. PMID- 11220429 TI - Dexamethasone prophylaxis of nausea and vomiting after epidural morphine for post Cesarean analgesia. AB - PURPOSE: To determine the minimum effective dose of dexamethasone in preventing nausea and vomiting associated with epidural morphine for post-Cesarean analgesia. METHOD: One hundred and eighty parturients (n=45 in each of four groups) requiring epidural morphine for post-Cesarean analgesia were enrolled in this randomized, double-blinded, placebo-controlled study. At the end of surgery, parturients received either dexamethasone, at doses of 10 mg, 5 mg, 2.5 mg, or saline i.v.. Three milligrams epidural morphine were given to all parturients for postoperative analgesia. The incidence of PONV and side effects were estimated for 24 hr after delivery by blinded, trained nurse anesthetists. RESULTS: Parturients who received dexamethasone, either 10 mg or 5 mg were different from those who received saline alone in the following parameters: the total incidence of nausea and vomiting, incidence of > 4 vomiting episodes, number the of parturients requiring rescue antiemetics, and the total number of parturients with no vomiting and/or no antiemetic medication (P < 0.05 to P < 0.01). The differences between dexamethasone 10 mg and 5 mg were not significant. Dexamethasone 2.5 mg was partially effective. CONCLUSION: Dexamethasone, 5 mg i.v., is suggested as the minimum effective dose in preventing nausea and vomiting associated with epidural morphine for post-Cesarean analgesia. PMID- 11220431 TI - Difficult separation from cardiopulmonary bypass and deltaPCO2. AB - PURPOSE: Veno-arterial and regional differences of the partial pressure in CO2 (deltaPCO2), may be used as index to evaluate the adequacy of the cardiac output to the oxygen consumption. To determine the incidence of elevated deltaPCO2 and its relationship with difficult separation from bypass (DSB) in patients undergoing cardiac surgery, we conducted a prospective observational cohort study. METHODS: Data were collected from 58 consecutive patients undergoing various cardiac operations requiring cardiopulmonary bypass (CPB). During the procedure, arterial and venous blood gases and lactate were sampled. Blood was drawn after induction of anesthesia, during bypass and at the closure of the chest wall. Difficult separation from bypass was defined as a systolic arterial pressure < 80 mmHg, and diastolic pulmonary artery pressure > 15 mmHg during progressive separation from CPB with inotropic or mechanical support of cardiac function, or hemodynamic instability resulting in reintroduction of extra corporeal circulation or insertion of an intra-aortic balloon pump. RESULTS: In our study, 65% of the samples were associated with elevated deltaPCO2 (> 6 mmHg). Variables associated with difficult weaning were LVEF; duration of bypass and aortic cross-clamping, pre-bypass deltaPCO2 and in-bypass lactate values (P < 0.05). Multivariable analysis identified the pre-bypass deltaPCO2 and the duration of bypass as predictors of DSB. CONCLUSION: Elevated deltaPCO2 is frequently observed during cardiac surgery and values obtained before bypass were associated with DSB. The deltaPCO2 gradients could be used as marker of the adequacy of tissue perfusion during cardiac surgery. PMID- 11220432 TI - Bilateral transient radial nerve palsies in an infant after cardiac surgery. AB - PURPOSE: To describe the case of an infant who suffered bilateral transient radial nerve palsies after cardiac surgery. CLINICAL FEATURES: A one-month-old baby was found to have bilateral wrist and finger drop after the removal of splints that has been applied to the right hand for 14 days and to the right hand for six days during perioperative management of Blalock-Taussig shunt surgery. The hand splints had been applied to the forearms with adhesive silky tape to keep peripheral vascular lines in place. The patient also suffered from several episodes of cardiogenic shock, hypoxemia and generalized edema relating to cardiac dysfunction during this fine period. Given the findings of no impairment of median or ulnar nerves and brachioradial muscle, it was suspected that bandaging with adhesive tapes caused peripheral radial nerve damage at the level of posterior interosseus nerve on forearm. Diminished oxygen delivery and edema may additionally have contributed to peripheral nerve ischemia. The aforementioned neurologic symptoms resolved spontaneously after several days. CONCLUSION: Prolonged compression by bandaging of splints on forearm may have resulted in ischemic damage to the posterior interosseus nerve branch combined with extensor carpi radialis longus nerve branch of the radial nerve. We should attempt to reduce the frequency and duration of splinting of the extremities, especially in sedated, paralyzed babies, given the potential risk of compression neuropathy. PMID- 11220433 TI - Successful management of venous air embolism with inotropic support. AB - PURPOSE: Since venous air embolism may occur during many different types of surgery, management of this clinical emergency can be required in patients who do not have a previously established central venous access for aspiration of air. Recent reviews suggest that management of right heart syndromes in patients with embolism is critical in improving outcome. CLINICAL FEATURES: Abrupt decreases in oxygen saturation (from 98% to 40%) and end-tidal carbon dioxide tension (from 24 to 6 mm Hg), compatible with venous air embolism were observed in a 73-yr-old woman during craniotomy for meningioma in the supine position. Since no access for aspiration of air was readily available, therapy was directed at inotropic support of the right heart using a bolus of ephedrine. Cardiorespiratory variables rapidly returned to normal, and the patient recovered from anesthesia and surgery without sequelae. CONCLUSIONS: Venous air embolism places an acute load on the right ventricle and may provoke right heart failure, even in the absence of total cardiovascular collapse. Treatment that supports right heart function may allow sufficient time for redistribution of embolized air and produce a good outcome when access for central aspiration of air is not available. PMID- 11220435 TI - Difficult airway management with the combination of a fibreoptic stylet and McCoy laryngoscope. PMID- 11220436 TI - Subcutaneous tunnelling of interscalene catheters. PMID- 11220437 TI - Postoperative bronchospasm in a patient with Parkinson's disease. PMID- 11220438 TI - Hidden misconnection of the pulse oximeter probe on a Seimens Medical Systems, Inc. KION anesthesia machine. PMID- 11220439 TI - Relationship orientation as a moderator of the effects of social power. AB - This research examined the hypothesis that the concept of power is mentally associated with different goals for individuals with a communal versus an exchange relationship orientation (M. S. Clark & J. Mills, 1979). It was predicted that communals associate power with social-responsibility goals, whereas exchangers link power with self-interest goals. Thus, when power is activated, distinct goals should be ignited for communals and exchangers. Power was primed unobtrusively using semantic cues in Study 1 and using naturally occurring, environmental cues in Studies 2 and 3. Across studies, power-primed communals responded in socially responsible ways, whereas power-primed exchangers acted more in line with their self-interests. These power-goal effects occurred nonconsciously. Overall, the data support taking a Person x Situation approach- one that allows for moderators such as relationship orientation--to understand power's positive and negative effects. PMID- 11220440 TI - Memory for in-group and out-group information in a minimal group context: the self as an informational base. AB - The authors argue that persons derive in-group expectancies from self-knowledge. This implies that perceivers process information about novel in-groups on the basis of the self-congruency of this information and not simply its valence. In Experiment 1, participants recalled more negative self-discrepant behaviors about an in-group than about an out-group. Experiment 2 replicated this effect under low cognitive load but not under high load. Experiment 3 replicated the effect using an idiographic procedure. These findings suggest that perceivers engage in elaborative inconsistency processing when they encounter negative self-discrepant information about an in-group but not when they encounter negative self-congruent information. Participants were also more likely to attribute self-congruent information to the in-group than to the out-group, regardless of information valence. Implications for models of social memory and self-categorization theory are discussed. PMID- 11220441 TI - Guilty pleasures and grim necessities: affective attitudes in dilemmas of self control. AB - Do self-control situations pit controlled reason against impulsive emotion, or do some emotions support the controlled choice? A pilot study of self-control attitudes found ambivalence between hedonic affect associated with short-term perspectives and self-conscious affect associated with the long term. In Study 1, negative self-conscious affect accompanied higher self-control among delayed-cost dilemmas ("guilty pleasures") but not delayed-benefit dilemmas ("grim necessities"). Study 2 showed that hedonic affect was more accessible than was self-conscious affect, but this difference was less among high self-control dilemmas. In Study 3, unobtrusively primed self-conscious emotion words caused dieters to eat less if the emotions were negative, more if positive. Hedonic positive and negative emotion words had the opposite effect. Self-conscious emotional associations, then, can support self-control if brought to mind before the chance to act. PMID- 11220442 TI - Covariational influences on goal-based explanation: an integrative model. AB - Covariational and goal-based approaches to social attribution have been treated as competitive or incommensurable. This article integrates key aspects of each approach. Four studies examined preferences for motivating factors (or goals) and enabling factors (or preconditions) as explanations of intentional actions. The studies manipulated (Studies 1-3) and measured (Study 4) the perceived covariation of these goal-based causes with target actions. Causes that covaried with actions were preferred explanations, in contrast with the goal-based view that motivating factors are generally preferred to enabling factors. Combining goal-based beliefs and covariational reasoning resolves problems faced by each individual approach and generates a novel explanatory typology that combines strengths of goal-based and covariational typologies. PMID- 11220443 TI - The connubial crucible: newlywed years as predictors of marital delight, distress, and divorce. AB - This study showed that couples' newlywed marriages and changes in their union over the first 2 years foreshadow their long-term marital fate after 13 years. Consistent with the enduring dynamics model, differences in the intensity of newlyweds' romance as well as the extent to which they expressed negative feelings toward each other predicted (a) whether or not they were happy 13 years later (among those who stayed married) and (b) how long their marriage lasted prior to separation (for those who divorced). The results provide little support for the idea that emergence of distress (e.g., increasing negativity) early in marriage leads to marital failure but instead show that disillusionment--as reflected in an abatement of love, a decline in overt affection, a lessening of the conviction that one's spouse is responsive, and an increase in ambivalence- distinguishes couples headed for divorce from those who establish a stable marital bond. PMID- 11220444 TI - Perceiver threat in social interactions with stigmatized others. AB - The extent to which stigmatized interaction partners engender perceivers' threat reactions (i.e., stigma-threat hypothesis) was examined. Experiments 1 and 2 included the manipulation of stigma using facial birthmarks. Experiment 3 included manipulations of race and socioeconomic status. Threat responses were measured physiologically, behaviorally, and subjectively. Perceivers interacting with stigmatized partners exhibited cardiovascular reactivity consistent with threat and poorer performance compared with participants interacting with nonstigmatized partners, who exhibited challenge reactivity. In Experiment 3, intergroup contact moderated physiological reactivity such that participants who reported more contact with Black persons exhibited less physiological threat when interacting with them. These results support the stigma-threat hypothesis and suggest the utility of a biopsychosocial approach to the study of stigma and related constructs. PMID- 11220445 TI - The dyadic nature of social information processing in boys' reactive and proactive aggression. AB - The correlation between boys' social cognitions and their aggressive behavior toward peers was examined as being actor driven, partner driven, or dyadic relationship driven. Eleven groups of 6 familiar boys each (N = 165 dyads) met for 5 consecutive days to participate in play sessions and social-cognitive interviews. With a variance partitioning procedure, boys' social-cognitive processes were found to vary reliably across their dyadic relationships. Furthermore, mixed models regression analyses indicated that hostile attributional biases toward a particular peer were related to directly observed reactive aggression toward that peer even after controlling for actor and partner effects, suggesting that these phenomena are dyadic or relationship oriented. On the other hand, the relation between outcome expectancies for aggression and the display of proactive aggression appeared to be more actor driven and partner driven that dyadic. PMID- 11220446 TI - Perceiving unfairness in the family: cause or consequence of marital distress? AB - This research tests a model suggesting that marital distress leads individuals to scrutinize what is given and received in the relationship. This scrutiny elicits perceptions of unfairness that maintain or exacerbate marital distress. In a 3 panel longitudinal study tracking married couples across the transition to parenthood, both wives' and husbands' reports of marital conflict and wives' marital dissatisfaction at Time 1 positively predicted perceived unfairness of the allocation of household tasks at Time 2, controlling for earlier perceptions of unfairness. In addition, there was evidence of perceived unfairness of division of labor at Time 2 predicting marital conflict and marital dissatisfaction for wives at Time 3, controlling for earlier conflict and dissatisfaction. This model of relationship distress and perceptions of unfairness is contrasted with prior interpretations of links between perceived injustice and distress in relationships. PMID- 11220447 TI - Why introverts can't always tell who likes them: multitasking and nonverbal decoding. AB - Despite personality theories suggesting that extraversion correlates with social skill, most studies have not found a positive correlation between extraversion and nonverbal decoding. The authors propose that introverts are less able to multitask and thus are poorer at nonverbal decoding, but only when it is a secondary task. Prior research has uniformly extracted the nonverbal decoding from its multitasking context and, consequently, never tested this hypothesis. In Studies 1-3, introverts exhibited a nonverbal decoding deficit, relative to extraverts, but only when decoding was a secondary rather than a primary task within a multitasking context. In Study 4, extraversion was found to correlate with central executive efficiency (r = .42) but not with storage capacity (r = .04). These results are discussed in terms of arousal theories of extraversion and the role of catecholamines (dopamine and norepinephrine) in prefrontal function. PMID- 11220448 TI - Distinguishing BIS-mediated and BAS-mediated disinhibition mechanisms: a comparison of disinhibition models of Gray (1981, 1987) and of Patterson and Newman (1993). AB - The theoretical framework developed by J. A. Gray (1981, 1987a, 1987b) was used to study disinhibitory behavior. Using a point-scoring reaction time procedure, 4 different experiments were conducted to differentiate 2 disinhibitory mechanisms associated with the behavioral activation system (BAS) and the behavioral inhibition system (BIS). Consistent with the work of C. M. Patterson and J. P. Newman (1993), the BAS-mediated mechanism was related to a lack of inhibition in reward-directed behavior after introducing an occasional aversive contingency and to deficits in learning from aversive cues when responding for reward (Experiments 1-3). The BIS-mediated mechanism was related to a higher ability to extinguish aversive associations (Experiment 1), a lower aversive generalization gradient (Experiment 3), and a lower interference with appetitive behavior in the presence of aversive stimuli (Experiment 4). PMID- 11220449 TI - What is satisfying about satisfying events? Testing 10 candidate psychological needs. AB - Three studies compared 10 candidate psychological needs in an attempt to determine which are truly most fundamental for humans. Participants described "most satisfying events" within their lives and then rated the salience of each of the 10 candidate needs within these events. Supporting self-determination theory postulates (Ryan & Deci, 2000)--autonomy, competence, and relatedness, were consistently among the top 4 needs, in terms of both their salience and their association with event-related affect. Self-esteem was also important, whereas self-actualization or meaning, physical thriving, popularity or influence, and money-luxury were less important. This basic pattern emerged within three different time frames and within both U.S. and South Korean samples and also within a final study that asked, "What's unsatisfying about unsatisfying events?" Implications for hierarchical theories of needs are discussed. PMID- 11220450 TI - Positive illusions about the self: short-term benefits and long-term costs. AB - Two studies addressed parallel questions about the correlates and consequences of self-enhancement bias. Study 1 was conducted in a laboratory context and examined self-enhancing evaluations of performance in a group-interaction task. Study 2 assessed students' illusory beliefs about their academic ability when they first entered college and then followed them longitudinally to test claims about the long-term benefits of positive illusions. Both studies showed that self enhancement bias was related to narcissism, ego involvement, self-serving attributions, and positive affect. Study 2 found that self-enhancement was associated with decreasing levels of self-esteem and well-being as well as with increasing disengagement from the academic context. Self-enhancement did not predict higher academic performance or higher graduate rates. Thus, the findings suggest that self-enhancing beliefs may be adaptive in the short term but not in the long term. PMID- 11220451 TI - Should we offer semen cryopreservation to men with testicular cancer? PMID- 11220452 TI - What is a practical approach to outpatient evaluation of diarrhea in a previously healthy, middle-aged patient? PMID- 11220453 TI - Changing patterns of morbidity and mortality in HIV disease. AB - In patients with HIV infection, highly active antiretroviral therapy is improving survival, but at the price of a variety of metabolic side effects. Patterns of morbidity and mortality are changing: the leading cause of death is now kidney or liver failure instead of opportunistic infections. PMID- 11220454 TI - Preventing sudden death in coronary cardiomyopathy: implantable defibrillators lead the way. AB - The Multicenter Unsustained Tachycardia Trial (MUSTT) demonstrated that electrophysiologic testing (EP)-guided therapy significantly reduces arrhythmic death and cardiac arrest in patients with coronary artery disease, a left ventricular ejection fraction of 40% or less, nonsustained ventricular tachycardia, and inducible ventricular arrhythmia on EP testing-but only if the therapy includes an implantable defibrillator. All patients who meet the MUSTT inclusion criteria should undergo an EP test and if positive, should undergo defibrillator implantation. PMID- 11220455 TI - Aggressive treatment of dyslipidemia: a review of supporting evidence. AB - Clinical trial data are now sufficient to support aggressive treatment of dyslipidemia. Cholesterol-lowering therapy is known to reduce the risk of clinical events across a wide range of lipid levels, even in patients with "normal" levels. Current data support lowering low-density lipoprotein cholesterol (LDL-C) levels at least to those recommended by the National Cholesterol Education Program, but perhaps even more aggressively in some patients. Of the available cholesterol-lowering agents, statins produce the greatest reductions in LDL-C levels and coronary events and are currently the best treatment option for most patients. PMID- 11220456 TI - Strategies to prevent progression of renal disease. AB - Clinical studies show that several strategies can prevent or slow the progression of renal disease in patients with or without diabetes. This paper reviews current theories of how renal disease develops and progresses and what clinical studies indicate about how to prevent or slow the process. PMID- 11220457 TI - Multiple sclerosis: the importance of early recognition and treatment. AB - Primary practitioners need to know how to expedite the diagnosis and treatment of multiple sclerosis (MS), because treatments that can slow its course appear to be most effective when started early. Several lines of evidence demonstrate that tissue damage occurs very early in the disease, and much of this damage is clinically silent. PMID- 11220458 TI - A lung-transplant recipient with infiltrates. PMID- 11220459 TI - Atrial septal defect repair. PMID- 11220460 TI - New findings in multiple sclerosis: a message for primary care clinicians. PMID- 11220461 TI - What is the risk of complications from cataract surgery in patients taking anticoagulants? PMID- 11220462 TI - Side branch preservation during endovascular aortic aneurysm repair. PMID- 11220463 TI - Fenestration in endovascular grafts for aortic aneurysm repair: new horizons for preserving blood flow in branch vessels. AB - PURPOSE: To describe techniques for deploying fenestrated stent-grafts that use partial graft deployment and guided tracking of the fenestration to the arterial orifice. TECHNIQUE: Fenestrations have been added to custom-made tube grafts and commercially manufactured Zenith stent-graft systems to preserve perfusion of aortic side branches. Partial device deployment, orientation markers on the endograft, and intraoperative angiography enable maneuvering of the fenestration over the orifice of the target vessel with the aid of guiding catheters. Placement of a Palmaz stent overlapping the fenestration and vessel orifice secures the junction. Two variations of fenestration have preserved blood flow in renal arteries during endovascular repair of abdominal aortic aneurysms (AAAs); similar techniques have maintained flow to the celiac axis in a thoracic aortic aneurysm. CONCLUSIONS: Accurate placement of a fenestration over the orifice of a target vessel is feasible, but long-term maintenance of position is dependent on secure graft fixation. This capability brings us a step closer to overcoming the problem of inadequate necks in infra-renal AAAs, especially when the neck is foreshortened by asymmetry of the renal origins. It may also pave the way for the eventual replacement of the entire aorta with an endoluminal graft. PMID- 11220464 TI - An endovascular system for thoracoabdominal aortic aneurysm repair. AB - PURPOSE: To describe a stent-graft system for endovascular repair of thoracoabdominal aortic aneurysm (TAAA) that preserves side branch perfusion. TECHNIQUE: The modular endograft system includes 3 components. The primary stent graft is custom-made from conventional graft fabric and Gianturco Z-stents. Covered nitinol Smart Stents are used for the visceral and renal extensions, and the distal extension is made from a modified Zenith system. With the supine patient under general anesthesia, the components are delivered sequentially through surgically exposed femoral and right brachial arteries in an operation that requires prolonged periods of magnified high-resolution imaging. This system was first used in a 76-year-old man with a contained rupture of a supraceliac ulcer and a large abdominal aortic aneurysm ending proximally at the celiac artery. The endograft was implanted successfully, but the patient developed paraplegia on day 2; imaging documented an excluded aneurysm and excellent flow through the endograft and all prosthetic branches. DISCUSSION: Endovascular repair of TAAA appears to be feasible. If there are no serious, specific, unavoidable complications, the potential advantages are enormous. PMID- 11220465 TI - Endoluminal aortic grafting with renal and superior mesenteric artery incorporation by graft fenestration. AB - PURPOSE: To explore the use of juxta- and suprarenal aortic segments for endograft fixation in abdominal aortic aneurysm (AAA) patients and to develop methods of graft implantation that use endograft fenestrations to preserve renal and visceral vessel perfusion. METHODS: From August 1998 to May 2000, 13 AAA patients with unsuitable infrarenal aortic necks were treated with custom designed endovascular grafts employing the juxta- and suprarenal aortic segments for proximal sealing. Flow to 33 renal and superior mesenteric arteries was maintained via graft fenestrations that were aligned by use of radiopaque graft markers. The fenestration-orifice interface for renal arteries was secured with modified balloon-expandable stents. RESULTS: All fenestrated grafts were deployed as planned, and all target vessels (33/33) were preserved. Two patients did not receive any stents, one being the first in the series and another who had incorporation of a renal accessory artery only. Without the use of transgraft stenting, 5 renal arteries would have been occluded by the endograft or poorly perfused. Procedural success was 100%. No conversion to open operation or graft related complications occurred. There was no primary endoleak in any patient by angiographic criteria. Two patients required additional surgical procedures related to access vessels. Periprocedural mortality at 30 days was nil. Follow-up ranging from 3 to 24 months on all patients has not demonstrated any proximal or distal endoleaks. One stented renal vessel has occluded; all other arteries remain patent at last examination. CONCLUSIONS: This study has demonstrated the ability to successfully place a multifenestrated endoluminal graft in an aortic aneurysm using juxta- and suprarenal aortic segments to obtain a satisfactory seal. Stenting of the fenestration-renal ostium junction has helped to maintain renal patency. PMID- 11220466 TI - Geometric changes in aortic endografts over a 2-year observation period. AB - PURPOSE: To report geometric changes in bifurcated aortic endografts observed over a 2-year follow-up period. METHODS: Twenty-two patients (21 men; mean age 68 years, range 57-83) with abdominal aortic aneurysms were treated with an endovascular stent-graft. Follow-up examinations included spiral computed tomographic scanning postoperatively and at 3, 6, 9, 12, 18, and 24 months after treatment. Geometric changes were measured using 3-dimensional reconstructed images in anteroposterior (AP) and lateral projections. Locations for the measurements were the proximal neck, the midportion of the endograft, and the graft limbs at the origin of the iliac arteries. RESULTS: Lateral changes predominated, demonstrating maximum angles on the side of the inserted left limb. For the proximal neck, the stent angle changed by a mean -0.71 degrees in the AP and 4.0 degrees in the lateral projection. At the midgraft, changes were -0.56 degrees for AP and 12.5 degrees for lateral. The right limb showed an angle of 6.43 degrees in AP and -0.43 degrees in lateral, whereas the left limb angles changed 1.38 degrees in AP and 11.71 degrees in the lateral plane after 2 years. There was no statistically significance difference in these changes from baseline. CONCLUSIONS: Aortic endografts are exposed to a significant amount of movement after insertion, but the resultant changes are very inhomogeneous, unpredictable, and ongoing even after 2 years. The most vulnerable location seems to be the attachment zone of the modular graft limb. These geometric changes might be one cause for late complications, including leaks and limb dislocations. PMID- 11220467 TI - Carotid artery stenting in patients with high-risk anatomy for carotid endarterectomy. AB - PURPOSE: To report the results of carotid artery stenting (CAS) in patients considered to have high-risk anatomical characteristics for carotid endarterectomy. METHODS: CAS was performed in 39 carotid arteries of 37 consecutive patients (26 men; mean age 72 +/- 8 years, range 56-88) who met the criteria for high-risk surgical anatomy: previous ipsilateral carotid endarterectomy (20/39, 51.3%), common carotid bifurcation above the mandibular angle (5/39, 12.8%), contralateral carotid artery occlusion (15/39, 38.5%), or previous radiation therapy to the neck (1/39, 2.6%). Palmaz, Integra, or Wallstents were deployed via a percutaneous femoral artery access. Independent neurological evaluation was performed at specified time points, and a dedicated committee adjudicated all clinical events. RESULTS: Procedural success was 100%, with no major in-hospital complications. Neurological events were rare. Only 1 (2.6%) transient ischemic attack occurred prior to discharge; at 30 days, 1 (2.6%) additional minor stroke had been observed, giving a 2.6% cumulative 30-day "death plus any stroke" rate. Over a mean 11 +/- 6-month follow-up, 2 (5.4%) patients died of nonneurological causes, but there were no strokes. CONCLUSIONS: CAS is a viable endovascular revascularization technique that can be performed safely and effectively in patients with high-risk anatomy for carotid endarterectomy. PMID- 11220468 TI - Characterizing the carotid revascularization candidate: will plaque morphology be important? PMID- 11220469 TI - The ICAROS registry of carotid artery stenting. Imaging in Carotid Angioplasties and Risk of Stroke. AB - ICAROS (Imaging in Carotid Angioplasties and Risk Of Stroke) is a multicenter international registry of carotid artery stenting designed to determine the criteria for identifying patients at higher or lower risk of periprocedural stroke and restenosis at 1 year. The aim of the registry is to improve patient selection and consequently reduce the risk of cerebral embolization during carotid stenting. The registry is open to all interventionists performing carotid stenting, and the participants are free to apply their own endovascular techniques and devices, including cerebral protection mechanisms. All cerebral ischemic events following the procedure will be reported. Follow-up surveillance to 1 year will include periodic duplex scanning and neurological examinations. Echographic plaque images will be standardized for comparison, processed for echodensity, and analyzed by computer at the Registry Center. Correlation will be investigated between the echographic index (gray-scale median) and the risk of embolism and outcome of carotid stenting. PMID- 11220470 TI - Endoluminal stent placement and coil embolization for the management of carotid artery pseudoaneurysms. AB - PURPOSE: To present a series of carotid artery pseudoaneurysms treated successfully using an endovascular approach. METHODS: From April 1995 to November 1999, 5 patients with neurological symptoms not explained by computed tomography of the head were identified by carotid angiography as having internal carotid artery (ICA) pseudoaneurysms. Three patients had sustained blunt trauma, and 2 had previous elective carotid endarterectomies for atherosclerotic disease. The time between injury and treatment ranged from 3 days to 10 years. The patients were treated with endovascular stent placement for exclusion of the pseudoaneurysm, followed by filling of the cavity with multiple detachable coils. Patients were maintained on oral antiplatelet agents or anticoagulant therapy after the procedure. RESULTS: Primary technical success was 100%. No patient suffered permanent neurological sequelae. Postprocedure angiography demonstrated a patent ICA in all cases, with complete obliteration of the pseudoaneurysm. At a mean 8.4-month follow-up (range 2-21), all patients remained symptom free; angiograms in 3 patients at a mean 11.7 months demonstrated continued ICA patency. One patient had a 60% focal narrowing of the distal common carotid artery, which was treated successfully with balloon dilation and stenting. CONCLUSIONS: Endovascular treatment of carotid artery pseudoaneurysms is a useful alternative to standard surgical repair. This modality avoids the necessity for surgical exposure at the skull base with its inherent morbidity. PMID- 11220471 TI - Combined endovascular and open surgery for four-vessel cerebrovascular occlusive disease. AB - PURPOSE: To report a case of bilateral simultaneous percutaneous transluminal angioplasty and stenting of the intracranial vertebral arteries prior to staged bilateral carotid endarterectomy. CASE REPORT: A 68-year-old man presented with a 3-month history of recurrent, intermittent left-sided weakness and diplopia. Imaging defined bilateral 80% to 99% internal carotid artery stenoses and >90% stenoses of both distal vertebral arteries at the level of the foramen magnum. Bilateral intracranial vertebral artery stenting was performed, followed by staged carotid endarterectomies. No complications occurred, and the patient recovered uneventfully from all 3 procedures. He remains symptom- and event-free 20 months later. CONCLUSIONS: Our initial success in this case indicates a role for percutaneous transluminal angioplasty and stenting as an alternative to open surgery for intracranial vertebral artery stenosis. PMID- 11220472 TI - Intracranial vertebral artery intervention: impressive and controversial. PMID- 11220473 TI - Percutaneous access and closure of femoral artery access sites associated with endoluminal repair of abdominal aortic aneurysms. AB - PURPOSE: To report longer follow-up and further experience using the Prostar XL Percutaneous Vascular Surgery (PVS) device for access and closure of large bore femoral artery access sites during endovascular repair of abdominal aortic aneurysms (AAAs). METHODS: One hundred forty-four patients (128 men; mean age 72 years, range 56-89) undergoing endovascular AAA repair had percutaneous access and closure of their 16-F femoral artery access sites using a 10-F PVS device. The first 54 patients were enrolled in the phase III trial of the AneuRx stent graft for AAA treatment. RESULTS: The femoral artery access site was successfully closed in 136 (94.4%) patients, with only 8 patients in whom adequate hemostasis could not be obtained. One-month follow-up was available in 144 patients, 6-month in 100, and 1-year in 59. No groin or lower extremity complications have been observed in any patient who had successful closure of the femoral artery access site. CONCLUSIONS: Large-bore femoral artery access sites can be percutaneously repaired using this device, which minimizes the invasiveness of the endograft procedure. PMID- 11220474 TI - Percutaneous profundaplasty in the treatment of lower extremity ischemia: results of long-term surveillance. AB - PURPOSE: To assess the procedural and long-term clinical outcomes of balloon angioplasty of the profunda femoris artery in patients with severe limb ischemia. METHODS: Thirty-one consecutive patients were evaluated for severe ischemia in 32 limbs: 13 (41%) were categorized Fontaine class 2B, and 19 (59%) were class 3 or 4. The superficial femoral artery was occluded in 20 (62%) limbs; an additional vessel was treated in 22 (69%) limbs. RESULTS: Procedural success was achieved in 91% (31/32) of limbs. The ankle-brachial index increased from 0.5 +/- 0.2 at baseline to 0.7 +/- 0.2 after intervention (p < 0.01). In-hospital limb salvage was 94% (30/32), and in-hospital event-free survival was 90% (28/31). At a mean follow-up of 34 +/- 20 months, no additional amputations were necessary; 3 patients required repeat revascularization, and 5 patients died. Freedom from revascularization was 88% in the 25 survivors. At follow-up, 88% of the patients had Fontaine class 1 or 2A symptoms, and only 12% had Fontaine class 2B or higher (p < 0.001 compared with baseline). CONCLUSIONS: These data suggest that percutaneous profundaplasty is safe, effective, and may be considered as an alternative to surgical therapy in patients with anatomically suitable lesions. PMID- 11220475 TI - Seat belt aorta: endovascular management with a stent-graft. AB - PURPOSE: To report the endovascular treatment of a relatively uncommon type of deceleration injury to the abdominal aorta. CASE REPORT: A 21-year-old backseat passenger was wearing a single lap belt without shoulder harness when the car was involved in a collision. He sustained a transverse (Chance) fracture of the third lumbar vertebra and a circumferential dissection of the infrarenal abdominal aorta with pseudoaneurysm. As an interim measure while a stent-graft was obtained, a Wallstent was deployed to tack down the dissection and prevent distal embolization. Thirty-six hours later, an AneuRx endograft was successfully implanted inside the Wallstent to seal the pseudoaneurysm. The patient's recovery was uneventful, and the endograft remains secure and the pseudoaneurysm excluded at 10 months after the accident. CONCLUSIONS: Endovascular repair of "seat belt aorta" is a minimally invasive, straightforward method of management for this type of aortic injury. The potential for infection in a contaminated peritoneal cavity and the long-term outcome of this treatment have not been determined. PMID- 11220476 TI - Sequential coil embolization of bilateral internal iliac artery aneurysms prior to endovascular abdominal aortic aneurysm repair. AB - PURPOSE: To report the endovascular repair of concomitant aneurysms of the abdominal aorta and both internal iliac arteries. CASE REPORT: A 72-year-old man with a 5.5-cm abdominal aortic aneurysm (AAA) extending to the right common iliac artery also presented with separate aneurysms of both internal iliac arteries. The patient refused conventional surgery, so an endovascular strategy was devised. Initially, the iliac aneurysms were sequentially coil embolized, allowing several weeks to elapse between the embolization sessions to encourage collateral development. A bifurcated Talent endograft was inserted successfully 8 months after the initial intervention; no evidence of endoleaks or mesenteric ischemia has been seen over a 1-year follow-up. CONCLUSIONS: This case illustrates the feasibility of inducing collateralization prior to endovascular AAA repair that would jeopardize internal iliac artery circulation bilaterally. Sequential embolization of the internal iliac arteries over several months initiates this response, paving the way for eventual endovascular repair of the primary aortic aneurysm. PMID- 11220477 TI - "Accordion" deformity of a tortuous external iliac artery after stent-graft placement. AB - PURPOSE: To identify a complication of endograft deployment in aneurysmal iliac arteries. CASE REPORT: A 71-year-old man was referred for endovascular treatment of a 60-mm-diameter right common iliac artery aneurysm; however, deployment of a homemade covered stent (Palmaz-Schatz and polytetrafluoroethylene) induced shortening of the tortuous external iliac artery, causing an "accordion" deformity. The anomaly proved difficult to treat with serial Wallstent deployment, because the convolution tightened and migrated caudally with each stent deployed, threatening outflow. Finally, after 3 Wallstents were implanted, the contour of the external iliac artery was straight, and flow was unimpeded. However, 3 weeks later, the external iliac artery had recoiled to its original redundant appearance, but flow remained satisfactory. The aneurysm remains excluded, with satisfactory distal flow after 24 months. CONCLUSIONS: Implanting endografts in redundant, tortuous arterial segments may prove problematic, since induced straightening by the device precipitates kinking in the redundant system. Although treatment may be required in some situations, the vessels may return to a noncompressed state by removing the delivery system and guidewire. PMID- 11220478 TI - Can the Gram's stain be used as a diagnostic tool? PMID- 11220479 TI - Evaluation of the strep B OIA test compared to standard culture methods for detection of group B streptococci. PMID- 11220480 TI - Vaginal-rectal colonization with group A streptococci in late pregnancy. AB - OBJECTIVE: To determine the vaginal-rectal colonization rate with group A streptococci in late pregnancy. METHODS: All patients delivering at a northern New England hospital over a 38 month period had 35-37 week vaginal-rectal swabs cultured for group A and group B streptococci, using selective media and slide agglutination. RESULTS: Six thousand nine hundred forty-four screening cultures were obtained. Among these 1,393 were positive for group B streptococci and 2 for group A streptococci, yielding colonization rates of 20.1% and 0.03%, respectively. CONCLUSIONS: Vaginal-rectal colonization with group A streptococci is rare, arguing against the need for establishing group A streptococcal screening programs in pregnancy. An approach for managing this uncommon finding is presented. PMID- 11220481 TI - Intrauterine infection and spontaneous midgestation abortion: is the spectrum of microorganisms similar to that in preterm labor? AB - OBJECTIVE: To determine whether microorganisms associated with intrauterine infection and preterm labor play a contributing role in midgestation abortion. METHODS: A 4 year retrospective review of spontaneous midgestation abortions for which autopsy and microbiological cultures of placental and fetal tissue were performed was conducted for a tertiary obstetrics hospital, which included a regional referral service for perinatal and fetal pathology. One hundred twenty nine spontaneously delivered, nonmacerated, midgestation fetuses or stillbirths (of between 16 and 26 weeks' gestation) and placentas were examined and cultured for aerobic and anaerobic bacteria, yeasts, and genital mycoplasmas. RESULTS: Microorganisms were recovered in 85 (66%) cases (57% placentas, 49% fetuses). Among the culture positive cases, 81% had histological chorioamnionitis, 28% fetal pneumonitis, 38% clinical signs of infection, and 62% ruptured membranes at the time of miscarriage. These differed significantly from culture-negative cases (44%, 5%, 13%, and 34%, respectively). Group B streptococcus (GBS) was the most significant pathogen, recovered in 21 cases, 13 as the sole isolate, 94% with chorioamnionitis, and 47% in women with intact membranes. Escherichia coli and Ureaplasma urealyticum (22 and 24 cases, respectively) occurred mostly as mixed infections, with ruptured membranes. GBS, MU urealyticum, and Streptococcus anginosus group were individually associated with chorioamnionitis, Bacteroides/Prevotella and S. anginosus with fetal pneumonitis. The spectrum of microorganisms was similar to that in preterm labor at later gestations; however, GBS appeared to be the most significant pathogen in midgestation miscarriage, especially with intact membranes. CONCLUSIONS: Unsuspected intrauterine infection underlies many spontaneous midgestation abortions. GBS is a key pathogen in this setting. PMID- 11220483 TI - Wound infection in gynecologic surgery. AB - OBJECTIVE: We sought to determine the wound infection rate among patients undergoing elective gynecologic surgery at a single tertiary care center and to determine the predictive value of various factors that contribute to infection. We further investigated the adequacy of hospital records in documenting infection rates as well as the timing of presentation of wound infections. METHODS: The records of 115 patients undergoing elective gynecologic surgery at our institution were reviewed. Patients were further subdivided based on route of surgery. We analyzed the importance of antibiotic prophylaxis, route of surgery, smoking, diabetes, and body mass index (BMI). RESULTS: The overall wound infection rate was 12.17% with no significant difference in the subgroups by route of surgery. Overall, antibiotic prophylaxis significantly decreased infection rates (P = 0.0118), but the route of surgery, BMI, smoking, and diabetes were not significant predictors of infection. Only one case of infection was detected during the initial hospital stay (6.1%). Fifty percent of the patients with infection required readmission, and of these 35.7% required an additional surgical procedure. The average length of hospital stay was 2.4 days longer in patients with infection. CONCLUSIONS: Antibiotic prophylaxis has a role in the management of patients undergoing abdominal gynecologic surgery. In today's environment of cost containment, an increased hospital stay and the added likelihood of additional surgical intervention associated with wound infection are important targets for prevention. Most patients with wound infection were diagnosed after discharge from the hospital. In our population, among whom transportation problems and remote residence are prevalent, strategies for infection surveillance should be integral to discharge planning. PMID- 11220482 TI - Ex vivo human placental transfer of trovafloxacin. AB - OBJECTIVE: The purpose of this study was to determine the ex vivo human placental transfer of trovafloxacin from the maternal circulation to the fetal circulation. METHODS: Six placentas from uncomplicated, term, vaginal or cesarean deliveries were studied using the ex vivo isolated cotyledon perfusion chamber; 14C antipyrine was used as a reference compound to determine the clearance index (CI) of trovafloxacin. RESULTS: The CI of trovafloxacin was 0.19 +/- 0.13 at a mean trough concentration of 1.38 +/- 0.22 microg/ml and 0.16 +/- 0.10 at a mean peak concentration of 7.48 +/- 2.3 microg/ml as determined by our newly developed high pressure liquid chromatographic assay. Tissue concentration did not exceed maternal concentration, and there was little or no accumulation when the perfusion system was closed for 1 hr. CONCLUSIONS: Trovafloxacin crosses the placenta by simple diffusion and does not accumulate in the media to any extent, nor does it bind to tissue or accumulate in the placenta. PMID- 11220484 TI - Prevalence of human papillomavirus, Chlamydia trachomatis, and Neisseria gonorrhoeae in commercial sex workers in Japan. AB - OBJECTIVE: We used the hybrid capture assays to investigate the prevalence of human papillomavirus (HPV), Chlamydia trachomatis and Neisseria gonorrhoeae among commercial sex workers in Tokyo. METHODS: Five hundred forty-six consecutive commercial sex workers (CSW) who visited an STD clinic for STD checkup in 1998 and 1999 were studied. A control group consisted of 233 consecutive women who visited a general gynecological clinic for annual checkup. A cervical sample was obtained for hybrid capture assays for HPV-A (low-oncogenic-risk types), HPV-B (intermediate- and high-oncogenic-risk types), C. trachomatis, and N. gonorrhoeae. Fisher's exact test was used for statistical analyses. RESULTS: The positive rate for HPV-B among the CSW was 48.4%, significantly higher than the 6.0% among the control subjects. The positive rates for HPV-A, C. trachomatis, and N. gonorrhoeae were also significantly higher among the CSW than among the control subjects. Among the microorganisms tested, the positive rate for HPV-B was the highest in both the STD and control groups. CONCLUSIONS: The high prevalence of HPV, C. trachomatis, and N. gonorrhoeae infection in CSW poses a risk of further transmission of STD to the general public, suggesting the need for further education and screening for CSW and the general public. We found high and intermediate-oncogenic-type HPV to be the most prevalent infection among both CSW and control subjects. Screening for HPV may be necessary in STD and general clinics to predict the risk of cervical malignancy. Hybrid capture assays, which permit simultaneous detection of HPV and other STD with high sensitivity, may be a useful diagnostic method. PMID- 11220485 TI - Terconazole cream for non-Candida albicans fungal vaginitis: results of a retrospective analysis. AB - OBJECTIVE: Although it is FDA-approved for use in vulvovaginal candidiasis caused by non-Candida albicans species, terconazole cream has not been been studied in patients with these infections. We sought to assess the clinical and mycological efficacy of terconazole cream in women with non-C. albicans vaginitis. METHODS: The records of patients who had received a 7-day course of terconazole cream for culture-proved non-C. albicans vaginitis were reviewed. Data with regard to patient demographics, clinical and mycologic response to therapy within 1 month of treatment, and outcome with other antifungal therapies were analyzed. RESULTS: Twenty-eight patients received terconazole cream for non-C. albicans infections. Three patients did not return for follow-up. The median age was 45 years. Seven (28%) patients were nulliparous. The median duration of symptoms was 3 years. Nine patients (36%) had received terconazole within the 6 months prior to referral. Overall, there were 20 C. glabrata cases, 3 C. parapsilosis, and 2 C. lusitaniae. Fourteen (56%) patients achieved a mycologic cure; 11 (44%) noted a resolution of their symptoms. Prior terconazole use was not associated with treatment failure (P = 0.09). Ten failures received boric acid suppositories as subsequent treatment; a cure was effected in 4 (40%). Two of three patients (67%) were eventually cured with flucytosine cream. Five (20 %) patients remained uncured. CONCLUSIONS: Terconazole cream may be an appropriate first-line treatment for non C. albicans vaginitis, even in patients who have previously received the drug. PMID- 11220486 TI - Value of Candida polymerase chain reaction and vaginal cytokine analysis for the differential diagnosis of women with recurrent vulvovaginitis. AB - OBJECTIVES: Recurrent vulvovaginitis remains difficult to diagnose accurately and to treat. The present investigation evaluated the utility of testing vaginal specimens from women with symptomatic recurrent vulvovaginitis for Candida species by polymerase chain reaction (PCR) and for cytokine responses. METHODS: Sixty-one consecutive symptomatic women with pruritus, erythema, and/or a thick white discharge and a history of recurrent vulvovaginitis and 31 asymptomatic women with no such history were studied. Vaginal swabs were tested for Candida species by PCR, for the antiinflammatory cytokine interleukin (IL)-10, and for the proinflammatory cytokine IL-12. RESULTS: C. albicans was detected in 19 (31.1%) of the patients as well as in three (9.7%) controls (P = 0.03). Both IL 10 (31.1% vs. 0%) and IL-12 (42.6% vs. 6.5%) were also more prevalent in the recurrent vulvovaginitis patients (P < 0.001). However, there was no relation between the presence or absence of Candida and either cytokine. Detection of IL 12 in 14 women indicated the stimulation of a vaginal cell-mediated immune response possibly from an infectious agent. The presence of only IL-10 in six patients indicated a suppression of vaginal cell-mediated immunity and was consistent with a possible allergic etiology. The absence of both IL-10 and IL-12 in other patients, similar to that found in healthy controls, suggested a noninfectious, nonallergic etiology of their symptoms. CONCLUSION: Many women with recurrent vulvovaginitis are not infected with Candida. Testing for Candida should be required in this population. Treatment with only anti-Candida medication will clearly be inadequate for the majority of women with this condition. PMID- 11220487 TI - Systematic review of diagnostic tests for vaginal trichomoniasis. AB - OBJECTIVE: To review critically and to summarize the evidence of diagnostic tests and culture media for the diagnosis of Trichomonas vaginitis. METHODS: We performed a systematic review of literature indexed in MEDLINE of studies that used Trichomonas culture as the reference standard (9,882 patients, 35 studies). Level I studies (5,047 patients, 13 studies) fulfilled at least two of three criteria: 1) consecutive patients were evaluated prospectively, 2) decision to culture was not influenced by test results, and 3) there was independent and blind comparison to culture. RESULTS: The sensitivity of the polymerase chain reaction technique (PCR) was 95% (95% CI 91% to 99%), and the specificity was 98% (95% CI 96% to 100%). One study was classified as Level I evidence (52 patients). The sensitivity of the enzyme-linked immunosorbent assay was 82% (95% CI 74% to 90%), and the specificity was 73% (95% CI 35% to 100%). The sensitivity of the direct fluorescence antibody was 85% (95% CI 79% to 90%), and the specificity was 99% (95% CI 98% to 100%). Sensitivities of culture media were 95% for Diamond's, 96% for Hollander, and 95% for CPLM. CONCLUSIONS: The sensitivity and specificity of tests to diagnose trichomoniasis vary widely. PMID- 11220488 TI - Dihydropyridine receptors functioning as voltage sensors in cardiac myocytes. AB - Isolated, superfused with [Ca2+]0 = 2.5-3 mM (T = 37 degrees C) and voltage clamped ventricular myocytes of guinea-pig hearts were stimulated by pulses from a holding potential -40 mV to +5 mV (duration 300 ms). They activated L-type Ca2+ current and a biphasic contractile response: a phasic component of amplitude approximately 7% of resting cell length (duration approximately 150 ms) and a tonic component of amplitude approximately 3% of resting cell length. The phasic component was inhibited by 10(-6) M thapsigargin (Tg). Pulses from -40 mV to +5 mV stimulated a similar bi-phasic contractile response in 74% of cells (n = 126) superfused from the beginning of a 30 s period of rest with 5-10 mM Ni2+ which blocked the Ca2+ current and Na+ -Ca2+ exchanger (Ni2+-contractions). Thus, the Ni2+-contractions could be activated only by intracellular Ca2+ release. The phasic component of control contractions showed the bell-shaped voltage relation at [Ca]0 = 2 mM and sigmoid relation at [Ca]0 = 3 mM. The phasic component o Ni2+ contractions showed a sigmoid relation at voltages from -40mV to +100 mV and could not be activated at [Ca]0 = 2 mM. It was inhibited by 20 microM nifedipine, a blocker of dihydropyridine receptors, even when activated by the pulses to +70 mV, during which the Ca2+ current does not flow. We proved that nifedipine does not affect Na+-Ca2+ exchange. The phasic component of Ni2+-contractions was also inhibited by 2 nM indolizinesulphone SR33557, another dihydropyridine receptor blocker, which halved the phasic component of contractions in sontrol cells without any significant effect on the Ca2+ current. Stimulation did not activate contraction in any of 19 cells in which 20 microM nifedipine was superfused from the beginning of 30 s rest instead of 5 mM Ni2+. These cells were depolarized to +5 mV over the rest period in order to prevent intracellular Ca2+ loss by Na+ Ca2+ exchange. Residual Ca2+ currents were much stronger in cells superfused with nifedipine than residual currents in cells superfused with Ni2+ (hardly visible in the records). Our results suggest that a vestigial remnant of a voltage sensing mechanism similar to that in the skeletal muscle may trigger the Ca2+ release from the SR of cardiac myocytes under specific experimental conditions. In normal cells it may be complementary to calcium induced calcium release (CICR). PMID- 11220489 TI - ATP-induced CA2+-signaling enhances rat gastric microvascular endothelial cell migration. AB - The effects of exogenous ATP on Ca2+ signaling and wound healing were investigated in rat gastric microvascular endothelial cells (RGMEC). ATP (10 microM) triggered a significant rise in intracellular Ca2+ concentration ([Ca2+]i) from 46+/-2 nM at baseline to peak values averaging 283+/-31 nM (n = 5 experiments, 132 cells). Return to the basal [Ca2+]i was delayed by slowly declining plateau phase that persisted for 200+/-30 s. Removal of extracellular Ca2+ did not significantly affect the peak rise in [Ca2+]i, but reduced the plateau. ATP (10 microM) also significantly increased the migration of RGMEC in a wounded monolayer. Addition of the non-subtype selective purinergic receptor antagonist, suramin, abrogated the effects of ATP on [Ca2+]i and migration. We conclude that local elevation of ATP acting through purinergic receptors induce Ca2+ signals in RGMEC and may contribute to endothelial cell migration. PMID- 11220490 TI - Isolation and characterization of rat gastric microvascular endothelial cells as a model for studying gastric angiogenesis in vitro. AB - We have previously characterized morphologic features of wounding-induced angiogenesis that occurs in response to acute and chronic gastric mucosal injury. As a means of investigating the molecular mechanisms underlying gastric angiogenesis, microvascular endothelial cells were isolated from stomachs of normal (non-injured) rats. The isolation procedure adapted and combined aspects of previous methods and employed positive selection using magnetic beads coated with monoclonal antibody specific for rat CD31 (PECAM-1), a cell surface marker restricted to platelets, monocytes, T lymphocytes and endothelial cells. The isolated microvascular endothelial cells expressed vascular endothelium-specific antigen and the endothelial-specific receptors, Tie2 and flt-1 (VEGFR1). When plated on growth factor-reduced matrigel, the isolated microvascular endothelial cells formed capillary-like structures reflecting in vitro angiogenesis. These cells were also responsive to vascular endothelial growth factor, VEGF, further verifying their endothelial nature. The rat microvascular endothelial cells isolated by this procedure should be useful in delineating molecular mechanisms and regulation of the angiogenesis that is essential for the healing of acute and chronic gastric injury. PMID- 11220491 TI - Sources of activator Ca2+ for galanin-induced contractions of rat gastric fundus, jejunum and colon. AB - Galanin (Gal) evoked reproducible contractions of isolated rat gastric fundus, colon and jejunum longitudinal strips in concentrations ranging from 1 nM to 3 microM. EC50 of Gal equalled 12.63, 23.27 and 56.02 nM, respectively. Hill's coefficients were not different from unity in any of the tissues examined. Experiments have been performed in the presence of protease and peptidase inhibitors, a variety of specific antagonists and tetrodotoxin (TTX) to exclude the non-specific stimulatory or inhibitory action of Gal. Gal-evoked contractions were attenuated by diminished extracellular Ca2+ concentration and by diltiazem. Gal activity in gastric fundus and colon, but not in jejunum was inhibited by depleting intracellular Ca2+ stores, thapsigargin, dantrolene, ryanodine, TMB-8, neomycin and U-73122. Our data confirmed that Gal contracts rat fundus, jejunum and colon by stimulating specific receptors, which are coupled both to Ca2+ influx through the voltage-dependent calcium channels and intracellular Ca2+ release from ryanodine- and IP3-sensitive stores (stomach and colon) or the extracellular Ca2+ influx only (jejunum). Phosphatidylinositol-specific phospholipase C (PI-PLC) plays a crucial role in the former but not in the latter signal transduction cascade. PMID- 11220492 TI - 5-HT1A receptor agonists buspirone and gepirone attenuate apomorphine-induced aggressive behaviour in adult male Wistar rats. AB - We have studied the effects of acute serotonin (5-HT) 5-HT1A receptor agonist buspirone (0.5, 1.0, 2.5 and 5.0 mg/kg, s.c.), gepirone (5.0 and 10 mg/kg, s.c.), and 8-OH-DPAT (0.1, 0.25, and 0.5 mg/kg, i.p.) treatment on the apomorphine induced aggressive behaviour in adult male Wistar rats. Buspirone in doses of 2.5 and 5.0 mg/kg completely blocked, gepirone (10 mg/kg) significantly attenuated the aggressiveness, and 8-OH-DPAT abolished aggressive behaviour only in the lowest dose used (0.1 mg/kg) which effect disappeared in higher doses. The antiaggressive effect of buspirone (2.5 mg/kg) and gepirone (10 mg/kg) was not reversed by a 5-HT1A receptor antagonist WAY 100635 (0.3 mg/kg). All 5-HT1A receptor agonists tested dose-dependently decreased the exploratory behaviour of experimentally naive rats, while buspirone (2.5 mg/kg) and gepirone (10 mg/kg) had only a weak effect on the locomotor activity and stereotyped behaviour in the apomorphine-pre-sensitised rats. In conclusion, our experiments demonstrate the 5 HTIA receptors may be involved in the mediation of the apomorphine-induced aggressive behaviour in adult male Wistar rats. However, the prominent antiaggressive effect of buspirone, and to a lesser extent--gepirone, seems to be mediated by some other mechanisms, evidently via the dopamine D2 receptors. PMID- 11220493 TI - The influence of increasing and decreasing frequency of stimulation on the contraction of motor units in rat medial gastrocnemius muscle. AB - Motoneurons during their activity can generate firings at changing rate. Therefore, the present paper aimed at studying the evoked contractions of different types of motor units to stimulation at progressively decreasing or increasing interpulse intervals. The influence of both patterns of stimulation on the tension, the duration and the tension-time area of motor units in rat medial gastrocnemius muscle was studied. The decreasing stimulation frequency resulted in generation of a bigger tension-time area although a slightly lower tension and a shorter duration of a contraction were observed in majority of studied units. For fast units a bigger tension-time area observed during the stimulation at decreasing frequency is probably due to the potentiation resulting from the initial high-frequency stimulation. On the other hand, at increasing frequency of stimulation the influence of the initial low-frequency stimulation can depress the tension-time area. The decreasing rate of stimulation during relaxation appeared to support the tension more effectively in slow-twitch motor units than in fast ones. Therefore, slow motor units are well suited to support the tension of tonic contractions. PMID- 11220494 TI - Effects of different intensities of cold stress on certain physiological phenomena related to skeletal health in a hypogonadal rat model. AB - Intestinal transference pattern of calcium and associated changes in the activities of intestinal mucosal enzymes, rate of bone turnover and bone metabolism were evaluated in ovariectomized rats exposed to cold stress of various intensities i.e., mild (15 degrees C) or stronger (8 degrees C and 4 degrees C) for 5 min everyday for 7 consecutive days. Except mild cold stress induced group (15 degrees C), rats of other two groups (8 degrees C and 4 degrees C) showed considerable decrease in the rate of in situ intestinal transference of calcium. Likewise, in these groups, the activities of intestinal mucosal enzymes, alkaline phosphatase (AP) and calcium ATPase (Ca2+-ATPase) were decreased significantly in all the segments of small intestine in a descending gradient. Also significant changes in bone turnover and bone resorption were confirmed in these animals by marked alterations in plasma AP activity, urinary calcium and phosphate excretion and urinary calcium to creatinine ratio (Ca: Cr). The skeletal changes were further ascertained by examining other physical and biochemical parameters of bone metabolism viz., body mass, bone density, ratio of mineral to matrix and mineral content of bone ash (calcium and phosphate) in the ovariectomized rat model. All these results suggest that stronger cold stress (8 degrees C and 4 degrees C) may be an important ecological factor in the development of earlier bone loss in hypogonadal rats. PMID- 11220495 TI - Age dependent changes of insulin receptors in rat tissues. AB - Aging is associated with insulin resistance but the exact molecular mechanism is still unknown. Tissue insulin resistance can be evoked by the decreased sensitivity to insulin, the decreased responsiveness to hormone or both. As the first step in insulin action is its binding to alfa subunits of the receptor we, therefore, studied the insulin binding kinetics in plasma membranes of the liver, heart and skeletal muscle in order to establish whether their ability to bind the hormone is altered with aging. Plasma membranes were prepared and purified according to Havrankowa and binding assay was performed using (125I)-iodoinsulin. The kinetic parameters of the hormone-receptor interaction were analysed by the method of Scatchard using the LIGAND-Pc v.3.1. computer program. The binding potency of insulin was calculated as IC50 using ALLFIT-Pc v.2.7. computer program. We have shown that there are striking differences in insulin binding kinetics in newborn and old rats, depending on kind of tissue tested. The liver plasma membranes ability for insulin binding, number of high (HAIR) and low (LAIR) affinity insulin receptors, values of the dissociation constants and products of association constants and number of insulin receptors, were almost the same, being not dependent on age of the rats. By contrast, there is less high affinity insulin receptors in skeletal muscle of the old animals. The most dramatic changes in insulin binding occur in the heart where both high and low affinity insulin receptors are greatly affected by aging. Our results indicate that the response of the three tissues tested to hyperglycemia and hyperinsulinemia, observed in the old rats, has not been identical and probably can be accounted for by the different distribution of insulin receptor isoforms in the liver, heart and skeletal muscles as shown recently by Vidal et al. PMID- 11220496 TI - The effect of dietary-induced obesity on lipid peroxidation, antioxidant enzymes and total plasma antioxidant capacity. AB - The aim of this study was to examine the effect of dietary-induced obesity on some parameters of oxidative stress and antioxidant defence. The studies were performed in adult male Wistar rats. Control group received normal laboratory chow (62% calories as carbohydrates, 26% protein and 12% fat). High-calorie high fat group (HCHF) was fed standard chow supplemented with lard (48% calories as carbohydrates, 20% as protein and 32% as fat) and high-calorie normal-fat group (HCNF) received standard chow and liquid diet containing sucrose, glucose, whole milk powder and soybean powder (60% carbohydrates, 26% protein, 14% fat). After 8 weeks body weight of HCHF and HCNF-fed rats was higher than body weight of controls by 9.3% and 15.2%, respectively. Plasma concentration of thiobarbituric acid-reactive substances (TBARS) increased in these groups by 43% and 52%, respectively. The activity of superoxide dismutase (SOD) decreased in HCHF group by 47.5% and in HCNF group by 21.1%. Glutathione peroxidase (GPx) activity in the blood tended to increase in both experimental groups but this was not significant. Plasma total antioxidant status (TAS) measuring the combined free radicals scavenging ability of nonenzymatic antioxidants was lower in HCHF and in HCNF group compared to control (-8.8% and -9%, respectively). The major observed lipid abnormalities were hypertriglyceridemia in HCHF group and decreased HDL cholesterol in HCNF group. TBARS correlated negatively with SOD (r = -0.84, p < 0.001) and with TAS (r = -0.47, p < 0.05). These results indicate that obesity leads to oxidative stress which can contribute to obesity-associated diseases such as atherosclerosis, diabetes mellitus and arterial hypertension. PMID- 11220497 TI - Central single and chronic administration of morphine stimulates corticosterone and interleukin (IL)-6 in adjuvant-induced arthritis. AB - Adjuvant-induced arthritis (AA) in the rat is a chronic inflammatory stress in which circulating corticosterone and interleukin (IL)-6 levels are elevated. In addition, there are profound neuroendocrine changes associated with the development of hind-paw inflammation which have major implications for the ability of the rat to respond to stress. Central injection of morphine is able to increase plasma corticosterone and circulating IL-6 concentration in control animals. In present study we have determined the effects of a single and repeated injection of morphine into the lateral ventricle of control and AA animals on plasma corticosterone, circulating IL-6 levels and course of hind-paw inflammation in AA rats. In the present study we found a sustained increase in plasma corticosterone both after single and repeated injection of morphine in control and AA rats and an increase of the level of circulating IL-6 in AA rats after repeated injection of morphine. These data suggest that alternative systems distinct from Athose activated in response to acute stress are activated by morphine in the AA animals. The similarity with the sustained increase in corticosterone following LPS injection suggest that central opiates may be involved in mediating HPA axis and cytokines response to inflammatory stress. PMID- 11220498 TI - Involvement of nitric oxide in central histaminergic stimulation of the hypothalamic-pituitary-adrenal axis. AB - Brain histamine participates in central regulation of the hypothalamic-pituitary adrenal (HPA) axis. Endogenous nitric oxide (NO) modulates signal transduction of some neurotransmitters involved in activation of the HPA axis. In the present study we investigated whether endogenous NO and histaminergic systems in the rat brain interact in their regulation of ACTH and corticosterone secretion. Histamine (50 microg), histamine-trifluoromethyl-toluidide derivative (HTMT, 75 microg) a selective and potent H1-receptor agonist, and amthamine (75 microg) a H2-receptor agonist given intracerebroventricularly (i.c.v.) considerably increased ACTH and corticosterone secretion 1 h after administration. A potent and competitive inhibitor of rat brain neuronal NO synthase, (NOS), 7 nitroindazole (7-NI), given i.p. 15 min before histamine moderately increased the histamine-induced ACTH secretion and did not substantially alter the histamine induced corticosterone secretion. Pretreatment with 7-NI totally abolished the HTMT-induced increase in ACTH and corticosterone secretion. The amthamine-evoked rise in ACTH secretion was moderately diminished and the amthamine-induced corticosterone secretion was not substantially altered by preatreatment with 7 NI. These results suggest that the histamine H -receptor transmited central stimulation of the HPA axis is considerably mediated by endogenous NO, whereas stimulation by histamine and via H2-receptor does not significantly depend on endogenous NO mediation. PMID- 11220499 TI - LH/hCG receptors in the porcine uterus--a new evidence of their presence in the cervix. AB - High-affinity LH/hCG binding sites have been characterized in bovine, lepine, murine, human uteri and porcine myometrium and endometrium. In the present studies we analyzed these receptors in the porcine cervix. Radioreceptor ligand assays were performed with cell membrane preparations of the cervix which were analyzed for binding sites specificity, capacity and affinity. Corpus luteum and myometrium were used as positive control tissues. In the cervix there was little competition for receptor occupancy between hCG and porcine FSH (1.2%) or bovineTSH, porcine GH and porcine PRL (0.1%, 0.1% and < 0.001%; respectively) but porcine LH could completely inhibit the binding of [125I] hCG. There was not binding for LH/hCG in crude membrane preparations of kidney or skeletal muscle. The concentration (fmol/mg protein) of cervical LH/hCG receptor did not vary significantly during particular phases of the estrous cycle, except the early luteal phase (Days 6-7) when the level of LH receptors was very low (p < 0.05). The affinity of uterine LH/hCG binding sites in the cervix and the myometrium was not different from the affinity of LH/hCG binding sites in luteal cells. The porcine cervix as well as the myometrium contains a 75- and 48-kDa immunoreactive LH/cCG receptor proteins similar to corpus luteum. Southern blot of RT-PCR products performed to enhance the specificity and sensitivity of LH receptor transcripts determination in uterine tissues revealed that expected fragments of 740 and 470 bp were present in myometrium and corpus luteum. The cervix showed only 740 bp fragment. In situ hydridization showed the expression of mRNA for LH receptor in the epithelium of the cervix. Immunoreactive staining for LH/hCG receptors was also observed only in epithelial cells of the cervical tissue. Our studies are probably the first evidence demonstrating the specific LH/hCG binding sites in female cervix. PMID- 11220500 TI - Role of calcitonin gene related peptide in the modulation of intestinal circulatory, metabolic, and myoelectric activity during ischemia/reperfusion. AB - Calcitonin gene related peptide (CGRP) is widely distributed in the myenteric neurons along GI tract. Biological effects of CGRP on gastrointestinal tract include increase in the intestinal blood flow, relaxation of the smoth muscle and slight increase in the slow wave amplitude (SWA) with no effect on frequency (SWF) of intestinal myoelectric activity (IMA). The aim of this study was to evaluate the possible protective effects of endo- and exogenous CGRP against ischemia/reperfusion (I/R) induced bowel injury in rats. Experiments were performed on 30 fasted anesthetized Wistar rats. Systemic arterial blood pressure (AP), mesenteric blood flow (MBF) and microcirculatory intestinal blood flow (LDBF) were measured. Oxygen consumption (VO2) was estimated from MBF and mesenteric AVO2 difference. IMA was recorded by 4 monopolar electrodes in proximal jejunum and analyzed using computer program with Fourrier analysis of SWF. Control ischemia induced by 30 min total occlusion of anterior mesenteric artery (AMA) reduced SWA by 25+/-5% and SWF by 24+/-4%. At the end of 60 minute reperfusion period SWA and SWF values were restored to control values but SWF showed instability. At the 15th minute of reperfusion period MBF, LDBF and VO2 increased to 109+/-6, 119+/-11 and 120+/-7% of control values respectively. Infusion of exogenous CGRP (0,16 microg/kg/min i.a.) increased MBF, LDBF and VO2 by 26+/-6, 31+/-9 and 20+/-4% respectively in comparison to control values. In the same experimental group SWA increase of 14% was observed with not significant changes in SWF. In the group where CGRP was administrated before and during 30 min period of intestinal ischemia MBF, LDBF and VO2 values at 15th minute of reperfusion were significantly higher by 24+/-6, 32+/-7 and 17+/-5% respectively in comparison to the values observed in the control reperfusion. In that group SWA values were restored to preocclusion values at 15th minute of reperfusion yet and SWF showed much more stability. Infusion of CGRP receptor antagonist (CGRP 8 37) reduced MBF, LDBF and VO2 by 12+/-7, 14+/-8 and 11+/-6% respectively (differences not significant versus control). In I/R group when CGRP 8-37 was given hemodynamic parameters (during reperfusion) were significantly lower and IMA parameters were not restored to preocclusion values. We conclude, that endogenous and exogenous CGRP attenuate circulatory parameters of the small intestine during ischemia and reperfusion. A direct correlation exists between hemodynamic, metabolic and myoelectric effects of CGRP. PMID- 11220501 TI - Gender differences in sexual behaviors and factors associated with nonuse of condoms among homeless and runaway youths. AB - Few studies have examined gender-specific factors associated with the nonuse of condoms among homeless and runaway youths (HRYs)-a population at high risk for HIV infection. In this article, we evaluate these factors and explore gender differences in background experiences, psychosocial functioning, and risk behaviors among HRYs from four U.S. metropolitan areas. Of 879 sexually active HRYs sampled, approximately 70% reported unprotected sexual intercourse during a 6-month period, and nearly a quarter reported never using condoms in the same period. Among males and females, having only one sex partner in the previous 6 months had the strongest association with nonuse of condoms. Among males, nonuse was also associated with having ever caused pregnancy, frequent marijuana use, prior physical victimization, and low self-control and sociability. Among females, nonuse was associated with knowledge of HIV status, prior sexual victimization, low social support, and infrequent marijuana use. These findings highlight the ongoing need for HIV prevention services for HRYs. Implications for the scope and content of these services are discussed. PMID- 11220502 TI - Examining communication and assertiveness as predictors of condom use: implications for HIV prevention. AB - The current study explored the relationship between communication and assertiveness in general and sexual contexts and examined each construct's differential ability to predict reported condom use among college students. The results suggest that the constructs are positively related to each other, but general communication does not predict sexual assertiveness. Although sexual assertiveness is a better predictor of condom use than general assertiveness, general communication, and sexual communication, it needs to be considered within the context of other variables (e.g., normative beliefs regarding condom use). HIV prevention programs and models of health behavior should incorporate individual characteristics such as sexual assertiveness. The results of this study suggest that sexual assertiveness, social norm perceptions of condom use, self-efficacy for HIV prevention, and condom attitudes are among the critical variables that should be examined in an integrated model of sexual health behavior. PMID- 11220503 TI - The impact of sexuality and race/ethnicity on HIV/AIDS risk among Asian and Pacific Island American (A/PIA) gay and bisexual men in Hawai'i. AB - The prevalence of HIV/AIDS in Asian and Pacific Island Americans (A/PIAs) has been relatively low in proportion to other racial/ethnic groups in the United States. However, HIV infection among A/PIA gay and bisexual men, and men who have sex with men has steadily increased in urban and other geographic areas with large Asian and Pacific Island populations. In this study of race/ethnicity and HIV risk among A/PIA gay and bisexual men in Hawai'i, respondents reported significant conflicts between loyalty to one's A/PIA family of origin and the enactment of individual sexual identity. Idealization of love and intimacy, intentional decisions to suspend safer sex practices, and Pacific Island cultural expressions of giving to others are all factors that may compromise HIV risk reduction in this population. Implications for HIV/AIDS prevention focus on integrating A/PIA, gay/bisexual, and "local" (born and raised in Hawai'i) identities in the development of multilevel interventions. PMID- 11220504 TI - Differences in disclosure of sexuality among African American and White gay/bisexual men: implications for HIV/AIDS prevention. AB - Gay and bisexual men were asked if they had disclosed their sexuality to family members, heterosexual friends, gay friends, coworkers, health care workers, and members of their church; if they had been associated with groups made up of gays, bisexuals, and lesbians; and if they had gay/bisexual friends. White men were much more likely to disclose their sexuality, to have associated with groups and to have gay/bisexual friends. As education increased, white men were more likely, and African American men less likely, to disclose sexuality and associate with groups. Having gay/bisexual friends increased with education with both groups. The difference in disclosure can be traced to the higher social stigma apparently attached to being gay in the African American community, which may be exacerbated for more educated men. As a result, African American gay men may be less likely to participate in the fight against HIV/AIDS. PMID- 11220505 TI - Women with HIV: conflicts and synergy of prayer within the realm of medical care. AB - In a recent survey of women with HIV, prayer was mentioned as a very important source in decision making about HIV antiretroviral therapy. As a follow-up to this finding, we conducted in-depth interviews with 51 women attending a comprehensive HIV care center to better understand the role of prayer in their decisions about taking antiretroviral therapy. The sample consisted predominately of African American (80%) women with a median age of 31 years from St. Louis and surrounding areas. Forty-seven (92%) reported that prayer was an important source for HIV medication decision making, with 30 (59%) considering prayer more important than the physician. Twenty-nine (57%) perceived a qualitative difference between prayer and the physician, which created a sense of conflict for some. Thirty (59%) wished that the physician knew more about the role of prayer in their lives. Our findings reveal compelling issues: (a) the willingness of the women to talk about prayer as a resource and its importance in HIV disease management, (b) the roles that prayer and the physician play in HIV medication decision-making, and (c) ways prayer can be addressed in a medical setting. PMID- 11220506 TI - Preventive attitudes towards the threat of AIDS: process and determinants in rural Senegal. AB - This report is intended to identify the determinants of preventive attitudes and thereby enable the further elaboration of effective prevention programs in a country where the HIV epidemic has remained controlled. Across-sectional survey using a standardized questionnaire was conducted among a sample of 866 adults of the general population of the rural area of Niakhar, Senegal. The analysis identified psychosocial determinants related to preventive attitudes and the influence of sociodemographic characteristics and of sources of AIDS information on these determinants. Psychosocial determinants of preventive attitudes differed according to gender: Among men, personal risk perception was associated with preventive attitudes. Among women, level of AIDS-related knowledge, communication about AIDS, and optimism about the future were associated with preventive attitudes. Sociodemographic factors and sources of information were similar for men and women: Preventive attitudes were adopted primarily by young, educated subjects who had been exposed to urban life. Religion appeared to be a major obstacle to preventive attitudes. Preventive messages broadcast on radio or television may be determinative. Our results call for a strengthened collaboration with religious leaders and a focus on risk perception to rationalize preventive actions. We also encourage the targeting of vulnerable populations, such as women in rural areas, by developing preventive messages to be delivered through national media (radio, television) and by staff from health centers, which most women visit, at least for prenatal care. PMID- 11220507 TI - Risk factors and characteristics of youth living with, or at high risk for, HIV. AB - Over 8,000 adolescents and young adults (4,111 males; 4,085 females) reported on several HIV-related risk behaviors during enrollment into 10 service demonstration projects targeted to youth living with, or at risk for, HIV. Distinct risk patterns emerged by gender when predicting HIV serostatus (versus unknown serostatus/negative serostatus). Males who had injection drug risk histories, had sex with an HIV positive partner, had sexually transmitted diseases, had sex with males, and/or were homeless had an inflated risk of being HIV positive. Females who engaged in sex with an HIV partner, had sex with an injection drug user, and/or had sexually transmitted diseases, were at the highest HIV risk. For both samples, engaging in sex with women reduced the likelihood of HIV positive status. Very basic information about risk factors obtained at service intake offers important information about HIV status of "high risk" youth presenting for care in community programs, as well as suggests clear risk factors for targeted preventive efforts. PMID- 11220508 TI - Differences in treatment and metabolic abnormalities between normo- and hypertensive patients with type 2 diabetes: the Skaraborg Hypertension and Diabetes Project. AB - AIM: To examine treatment and glucose control in type 2 diabetes patients with and without hypertension, and to explore differences in markers for insulin resistance and beta cell function. METHODS: A community-based, cross-sectional observational study was carried out at the hypertension and diabetes outpatient clinic in primary health care, Skara, Sweden. The subjects were all the 400 patients with type 2 diabetes (202 men, 198 women) who underwent annual follow-up from May 1992 through September 1993; 204 of these also had hypertension. RESULTS: The patients with both type 2 diabetes and hypertension had a higher b.m.i. (mean; 28.9 kg m(-2) (s.d.; 4.4) vs. 27.4 kg m(-2)(4.6)), higher triglycerides (2.0 mmol l(-1)(1.1) vs. 1.7 mmol l(-1)(1.1)), higher LDL/HDL cholesterol ratio (4.3(1.4) vs. 4.1(1.2)) and higher fasting insulin (8.5 mU l( 1)(1.1) vs. 6.6 mU l(-1)(1.1)). Conversely, glucose levels were lower; HbA1c (6.4%(1.4) vs. 6.8%(1.6)) and fasting blood glucose (8.1 mmol l(-1)(2.3) vs. 8.9 mmol l(-1)(2.7)) than in patients with type 2 diabetes alone. By the homeostasis model assessment (HOMA), patients with type 2 diabetes alone had more impaired beta cell function. They also had a higher frequency of insulin treatment (20% vs. 12%) and were less often treated non-pharmacologically (33% vs. 50%). CONCLUSIONS: Patients with type 2 diabetes and hypertension constitute a high risk category with a more atherogenic risk factor profile related to the insulin resistance syndrome. Patients with type 2 diabetes without hypertension seem to constitute a subgroup of type 2 diabetes with predominately impaired beta cell function. PMID- 11220513 TI - FDA reviews troglitazone. PMID- 11220509 TI - Gliclazide reduces the induction of human monocyte adhesion to endothelial cells by glycated albumin. AB - OBJECTIVE: To examine the kinetic of human monocyte adhesion to endothelial cells stimulated by glycated albumin, the contributive role of cell adhesion molecules to this effect, and the effect of gliclazide--an hypoglycemic drug with antioxidant properties--on these parameters. METHODS: In-vitro experiments performed in the presence and absence of gliclazide consisted of: (1) time dependent determination of human monocyte adhesion to human endothelial cells (ECs) pre-exposed to glycated albumin; (2) evaluation of adhesion after incubation of ECs with antibodies against cell surface adhesion molecules; and (3) determination of EC surface adhesion molecules and of the activity of the transcription factor NF-kappaB. RESULTS: Exposition of human ECs for 1-48 h to 100 microg/ml glycated albumin led to a time-dependent increase in human monocyte adhesion to endothelium. Pretreatment of ECs with 10 microg/ml gliclazide significantly decreased the glycated albumin-stimulated monocyte adhesion to these cells. Anti-antibodies against E-selectin (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) also reduced the stimulatory effect of glycated albumin on monocyte adhesion. In glycated albumin-treated ECs, an induction of both soluble and cell associated expression of ELAM-1, VCAM-1 and ICAM-1, an augmentation in the levels of these molecule transcripts and an increase in the DNA binding activity for NF-kappaB in the promoters of these antigens were observed. Gliclazide markedly inhibited the induction of all these parameters. CONCLUSIONS: Glycated albumin stimulates human monocyte adhesion to ECs by inducing cell associated ELAM-1, ICAM-1 and VCAM-1. Gliclazide effectively inhibits monocyte adhesion to ECs by reducing glycated albumin induction of EC adhesion molecules and NF-kappaB activation. These results suggest that gliclazide may be beneficial in the prevention of endothelial disturbances associated with hyperglycemia in diabetic patients. PMID- 11220514 TI - Early intensive insulin treatment for induction of long-term glycaemic control in type 2 diabetes. PMID- 11220515 TI - In-vivo and in-vitro models of type 2 diabetes in pharmaceutical drug discovery. PMID- 11220516 TI - Isolation of human islets and beta-cells for pharmacological studies. PMID- 11220517 TI - A beta3-adrenergic agonist increases muscle GLUT1/GLUT4 ratio, and regulates liver glucose utilization in diabetic rats. AB - AIM: Previous studies have reported that beta3-adrenergic agonists reduce plasma glucose levels in situations of hyperglycaemia and diabetes in rodents. Nevertheless, the mechanisms still remain unclear. In this context Trecadrine, a novel compound with affinity for beta3-adrenergic receptors, has been tested in alloxan-diabetic rats for its potential use as an anti-diabetic drug, but also to elucidate the role of muscle/liver glucose utilization in the process. METHODS AND RESULTS: Daily oral administration (1 mg/kg) to alloxan-diabetic Wistar rats (n = 10) for 4 days caused a significant reduction in plasma glucose levels (from 15.0 to 8.3 mmol/l) with no apparent effects on insulin secretion. Furthermore, Trecadrine administration tended to normalize glucose storage (estimated by measuring glucokinase activity) and output (by measuring glucose-6-phosphatase activity) in the liver of diabetic animals. On the other hand, Trecadrine administration for 4 days resulted in an increase in GLUT1 gene expression in gastrocnemius muscle as compared to insulin-dependent glucose transporter GLUT4. Furthermore, a significant stimulation of 2-deoxy-D-glucose uptake in extensor digitorum longus muscle and, in a lesser degree, in gastrocnemius, but not in soleus muscle and in white adipose tissue, occurs. CONCLUSIONS: Trecadrine reduces glucose output from the liver, thus thus contributing to the reduction of plasma glucose levels to achieve the values of control rats. Furthermore, Trecadrine administration stimulates glucose uptake in skeletal muscle, especially in those muscles with predominant glycolytic fast-twitched fibres, apparently by a direct non-insulin-dependent mechanism, involving a relative increase in the content of GLUT1 in the plasma membrane as compared with GLUT4. In conclusion, Trecadrine shows a potent hypoglycaemic effect in the alloxan induced model of diabetes in rats by decreasing hepatic glucose output and improving muscle glucose uptake. PMID- 11220518 TI - Maintenance of sinus rhythm as a therapy goal. AB - Despite recent advances in our understanding of the mechanisms and consequences of atrial fibrillation, appropriate management of this common condition presents something of a dilemma. Control of ventricular rate alone is a common strategy, considered by many physicians to be the safest treatment option and a relatively simple approach to preserving left ventricular function. Rhythm control using antiarrhythmic agents, however, offers a number of important advantages, with the potential to correct abnormal physiology, increase exercise tolerance, reduce thromboembolic risk, prevent atrial remodelling and eliminate the risk of tachycardia-induced cardiomyopathy. Selection of an appropriate antiarrhythmic agent for such long-term prophylaxis is however problematic. Class I agents are associated with an unacceptable proarrhythmic risk especially in patients with structural heart disease and long-term therapy with the class III agent amiodarone can result in serious non-cardiac adverse effects. It is apparent, therefore, that there is little consensus on appropriate management strategies for atrial fibrillation and less still on the antiarrhythmic agent to be used. A number of studies are, however, ongoing which attempt to determine the benefits of rhythm versus rate control. These include the PIAF (Pharmacological Intervention in Atrial Fibrillation), AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) and RACE (Rate Control versus Electrical Cardioversion) studies, which should provide valuable answers which will help to guide physicians in their therapy choices. PMID- 11220519 TI - The role of class III antiarrhythmic agents in maintaining sinus rhythm. AB - The last decade has seen considerable changes in both attitude and approach to the management of arrhythmia. Much of this has resulted from trials such as the CAST (Cardiac Arrhythmia Suppression Trial) and the CASH (Cardiac Arrhythmia Study Hamburg), which demonstrated the potentially lethal consequences of using class I sodium channel blockers in patients with structural heart disease. The subsequent popularity of the class III agents and recognition that they are the best available therapy has led to the popularity of amiodarone and sotalol in the treatment of arrhythmia. Although these agents can achieve good efficacy in the suppression of atrial fibrillation their use is not without problems. Sotalol requires careful patient selection due to the risk of proarrhythmia and although cardiac effects are rare with amiodarone therapy, potentially serious non-cardiac adverse effects can limit the long-term use of this agent. Although treatment guidelines have helped to clarify our current knowledge and outline appropriate clinical application of antiarrhythmic agents, the need for antiarrhythmic agents which marry efficacy with improved safety and clinical applicability is apparent. PMID- 11220520 TI - Clinical differences between the newer antiarrhythmic agents. AB - In the light of studies demonstrating the serious safety problems of antiarrhythmic agents with class I activity, research and development efforts have focused largely on drugs with a class III mechanism of action. Most of the newer agents target the rapid component of the delayed rectifier potassium current (I(Kr)). In the case of dofetilide, the mechanism of action is relatively pure, with single I(Kr) channel blocking activity. Other agents have a wider spectrum of activity. Azimilide blocks both the rapid I(Kr) and slow I(Ks) potassium currents and ibutilide also augments the inward sodium current. Clinical investigation of these agents has shown them to be effective antiarrhythmic drugs with a number of advantages over existing agents, particularly in terms of safety. Dronedarone and tedisamil also have multichannel blocking actions and are in earlier stages of clinical development. Until now, therapeutic choices have been limited and far from ideal. It is hoped that the availability of the newer class III agents will at least provide greater choice of therapy and hopefully will bring us closer to therapeutic ideals in the management of arrhythmia. PMID- 11220521 TI - Mechanisms of action of class III agents and their clinical relevance. AB - Antiarrhythmic agents are broadly classified according to their mode of action in order to provide a basis for rational drug choice when managing particular rhythm disturbances. However, a great deal of variability exists within each drug class and treatment decisions require a greater understanding of the pharmacological characteristics of individual drugs in order to tailor treatment to a specific clinical presentation. Class III drugs in particular form a heterogeneous group of agents, some of which selectively block ion channels while others have multi channel blocking properties. An improved understanding of the relevance of the specific mechanism of action is now proving essential in predicting the value of individual drugs in clinical practice. Selective I(Kr) blocking agents increase action potential duration and refractoriness to the greatest extent at slow rates. Therefore, efficacy may be reduced at higher heart rates, the situation in which serious arrhythmias are most likely to occur. This so-called 'reverse use dependence' can be overcome with certain drug combinations, such as sotalol plus either quinidine or procainamide, drugs with multi-channel blocking properties, such as amiodarone, and possibly with drugs which block the I(Ks) as well as the I(Kr) potassium current, such as azimilide and ambasilide. PMID- 11220524 TI - Shape up and drop 10. PMID- 11220523 TI - Rosiglitazone. PMID- 11220522 TI - Sibutramine is effective for weight loss and diabetic control in obesity with type 2 diabetes: a randomised, double-blind, placebo-controlled study. AB - AIM: To assess the efficacy and tolerability of sibutramine 15 mg once daily as a weight reduction agent in overweight and obese patients (body mass index (b.m.i.) > 26 kg/m2) with type 2 diabetes when given with a customised, reduced-calorie diet, and to evaluate the influence of weight loss on diabetic control. METHODS: Randomised, placebo-controlled, double-blind, parallel-group, 12-week study conducted at two hospital-based obesity/diabetes clinics. Patients were men and women aged 30-65 years, with b.m.i. > 26 kg/m2 and < or = 35 kg/m2 and treated or untreated type 2 diabetes diagnosed > or = 6 months previously. Each patient was given sibutramine 15 mg or placebo once daily and advised to follow a customised diet of 500 kcal/day less than the individual's energy needs. The principal measure of efficacy was change in body weight (b.w.). Additional efficacy measurements were changes in b.m.i., body composition as measured by dual-energy X-ray absorptiometry, and change in waist and hip measurements. Changes in diabetic control were assessed by blood glucose levels fasting and after a standard test meal, fasting insulin level, and glycosylated haemoglobin level. Adverse events (AEs) were monitored at each visit, and routine laboratory safety tests were done at 4-week intervals. RESULTS: Ninety-one patients were randomised into the study, 44 to placebo and 47 to sibutramine 15 mg once daily. Eighty three patients (91%) completed the study, 40 (91%) on placebo and 43 (91%) on sibutramine. Mean weight reduction from baseline was statistically significantly greater with sibutramine than with placebo at every measurement and at the end of the study (2.4 vs. 0.1 kg at week 12; p < 0.001; intent-to-treat). The proportion of patients who lost > 5% of their baseline b.w. was 19% in the sibutramine group and 0% in the placebo group (p < 0.001; 95% confidence interval: 9, 30). Patients receiving sibutramine lost significantly more fat mass compared with those receiving placebo, as a percentage (1.0% vs. 0.1%; p < 0.05) and in absolute terms (1.8 vs. 0.2 kg, p < 0.001). Loss of lean mass was not significantly different between the groups. Mean peak blood glucose concentration after a standard test meal decreased by 1.1 mmol/l in the sibutramine treatment group but increased by 0.5 mmol/l in the placebo group (p = 0.04; difference in means, 1.6, 95% confidence interval: -3.3, -0.1). Mean fasting blood glucose decreased by 0.3 mmol/l with sibutramine and increased by 1.4 mmol/l with placebo. Mean glycosylated haemoglobin levels decreased by 0.3% units with sibutramine treatment, and were unchanged with placebo. However, more sibutramine-treated patients (33%) than placebo-treated patients (5%) achieved decreases in glycosylated haemoglobin of 1% unit or more (p < 0.05). Sibutramine 15 mg was safe and well tolerated, and AEs were mostly mild or moderate in severity. No significant differences were found between treatment groups in blood pressure. No clinically significant conduction or rhythm abnormalities were observed on ECG. CONCLUSIONS: Sibutramine 15 mg once daily with a customised, reduced-calorie diet significantly reduced weight compared with placebo in overweight and obese patients (b.m.i. > 26 kg/m2) with type 2 diabetes. Sibutramine was well tolerated, and significant improvement in diabetic control was seen in conjunction with weight reduction on sibutramine treatment. PMID- 11220525 TI - Expanding immuno-therapies for type 1 diabetes. PMID- 11220527 TI - Hypoglycaemia and associated hypokalaemia in diabetes: mechanisms, clinical implications and prevention. PMID- 11220526 TI - Cardiovascular effects of sulphonylureas: role of K(ATP) channels. PMID- 11220528 TI - The future of leptin and leptin analogues in the treatment of obesity. PMID- 11220529 TI - Ethnicity and risk factors for coronary heart disease in diabetes mellitus. AB - INTRODUCTION: The Framingham equation can be used to predict the risk of coronary heart disease (CHD) and so to target risk factor intervention. Reservations have been applied to its use in south Asian populations since the high CHD mortality in this group may not be accounted for by traditional risk factors. METHODS: We applied the Framingham equation to 1826 patients with diabetes of whom 1215 were of white Caucasian and 611 south Asian origin. Having calculated the 10-year CHD risks the contribution of risk factors were compared between ethnic groups. RESULTS: Mean 10-year CHD risk was the same in the two ethnic groups (20.7 vs. 21.5%, white Caucasian vs. south Asian men and 16.5 vs. 15.9%, white Caucasian vs. south Asian women). However, the risk factor profile was different between the two groups. Mean total cholesterol was lower in south Asians (5.23 vs. 5.41 mmol/l, south Asian vs. white Caucasian men (p = 0.01) and 5.38 vs. 5.68 mmol/l, south Asian vs. white Caucasian women (p < 0.001)). HDL cholesterol levels were also lower (median HDL cholesterol 0.94 vs. 1.11 mmol/l, south Asian vs. white Caucasian men (p < 0.001) and 1.07 vs. 1.3 mmol/l, south Asian vs. white Caucasian women (p < 0.0001)) leading to higher total: HDL cholesterol ratios (5.48 vs. 4.78, south Asian vs. white Caucasian men (p = 0.032) and 4.91 vs. 4.26, south Asian vs. white Caucasian women (p < 0.001). CONCLUSION: Calculated 10-year CHD risks are the same in south Asian and white Caucasian diabetic patients but the factors contributing to this risk differ. Different management of these risk factors may account for the higher mortality from CHD in those of south Asian origin. PMID- 11220530 TI - Disturbed release of gastrointestinal peptides in anorexia nervosa and in obesity. AB - AIM: It is commonly accepted that some neuropeptides play an important role in the control of appetite and hormonal secretion. Several gastrointestinal peptides may affect on central control of appetite via vagal and spinal nerves. The aim of this study was to evaluate the release of gastrointestinal peptides in anorexia nervosa and in obesity, because in these diseases the disturbances in the control of appetite and hormonal secretion were found. Material consisted of 30 women with anorexia nervosa aged 16-29 years (mean 22 years) and 23 women with obesity aged 19-33 years (mean 29 years) and 25 lean women of control group. METHODS: In women with anorexia nervosa as compared with control group we observed a significant increase of plasma vasoactive intestinal peptide (VIP) levels (p < 0.01) and a significant decrease of leptin (p < 0.001), beta-endorphin (p < 0.01), gastrin (p < 0.05), cholecystokinin (CCK; p < 0.05) and somatostatin (S-S; p < 0.01). In obese women we found a significant increase of neuropeptide Y (NPY; p < 0.001), leptin (p < 0.01), galanin (p < 0.001), beta-endorphin (p < 0.001), gastrin (p < 0.01), CCK (p < 0.001) and S-S (p < 0.01) and a significant decrease of VIP concentrations (p < 0.001) as compared with control group. CONCLUSION: Our results indicate that the release of gastrointestinal peptides is disturbed in obesity and in anorexia nervosa. These findings suggests that dysfunction of brain-gut axis may be also an important factor in the abnormal control of appetite axcept of hypothalamic dysfunction. PMID- 11220532 TI - Atrioventricular junctional ablation and pacing for paroxysmal atrial fibrillation: the Barcelona recommendations. PMID- 11220531 TI - Prospective, randomized study of atrioventricular ablation and mode-switching, dual chamber pacemaker implantation versus medical therapy in drug-resistant paroxysmal atrial fibrillation. The PAF study. Paroxysmal Atrial Fibrillation. AB - We performed a prospective randomized 6-month evaluation of the clinical effects of atrioventricular junctional ablation together with placement of a DDDR mode switching pacemaker vs pharmacological treatment in 43 patients with intolerable paroxysmal atrial fibrillation not controlled with antiarrhythmic drugs. Ablation and pacemaker treatment were highly effective and superior to drug therapy in controlling symptoms and improving quality of life. However, discontinuation of drug therapy exposed patients to further recurrences of paroxysmal atrial fibrillation and the risk of developing permanent atrial fibrillation. PMID- 11220533 TI - Prospective, randomized study of atrioventricular node ablation and mode switching, dual chamber pacemaker implantation using two different algorithms in patients with paroxysmal atrial fibrillation. PMID- 11220534 TI - The North American experience with the Ablate and Pace Trial (APT) for medically refractory atrial fibrillation. AB - The Ablate and Pace Trial (APT) was a prospective registry study of clinical outcomes and survival following ablation and pacing therapy for medically refractory atrial fibrillation. One hundred and fifty-six patients were enrolled at 16 centres in North America. The mean patient age was 66 +/- 11 years, with mean left ventricular ejection fraction of 48% +/- 18%. Seventy-eight percent of the patients had structural heart disease. During one year of follow up, multiple measures of quality-of-life showed significant and sustained improvement following ablation and pacing therapy. Also, left ventricular ejection increased significantly for patients with baseline left ventricular ejection fraction <45%. Metabolic exercise testing showed trends toward improved exercise tolerance; however, these did not achieve statistical significance. The one year overall survival was 85%, with 3% of patients experiencing sudden death. In summary, this large, non-randomized, trial showed significant improvement in quality of life and left ventricular function following ablation and pacing therapy. Ablation and pacing therapy is a viable strategy for palliative management of patients with medically refractory, highly symptomatic atrial fibrillation. PMID- 11220535 TI - Ablation of the atrioventricular junction: technique, acute and long-term results in 115 consecutive patients. AB - Atrioventricular junctional ablation is an attempt to interrupt conduction from the atrium to the ventricle using radiofrequency energy. The objective is to ablate the compact atrioventricular node as high as possible, leaving a stable ventricular escape rhythm. The compact node is identified in part by its relation to His recordings and partly through the known anatomy. In our series of 115 consecutive patients, atrioventricular block was achieved from the right side in 96% of patients and the remainder had the atrioventricular node ablated from the left side. Long-term success, i.e. complete heart block, was achieved in all patients. Complications in this and other series are rare, but there remains concern about sudden death in these patients. PMID- 11220536 TI - Chronic atrial fibrillation in patients with paroxysmal atrial fibrillation, atrioventricular node ablation and pacemakers: determinants and treatment. AB - AIMS: This study examined the factors associated with the development of chronic (or permanent) atrial fibrillation (AF) in patients who had undergone atrioventricular (AV) node ablation with permanent pacing because of paroxysmal AF. METHODS: A retrospective review of case notes of all 65 consecutive patients identified as having had paroxysmal atrial arrhythmias, AV node ablation and permanent pacemaker implantation was performed. Atrial rhythm was established from all pacing records and from the surface ECG. Treatment with anti-arrhythmic drugs and with warfarin was recorded. A multivariate analysis was undertaken, using atrial rhythm on final ECG and chronic AF as outcome measures. RESULTS: During a mean follow-up of 30 months, 42% of patients with paroxysmal AF had developed chronic AF. Multivariate analysis showed that increasing age, history of electrical cardioversion and VVI pacing all contributed to the development of chronic AF. 25/62 patients were taking warfarin, and four had had strokes (2.5%/year). CONCLUSION: The majority of patients with paroxysmal atrial arrhythmias treated with AV node ablation and pacing develop chronic AF eventually. Stroke remains a risk, particularly in those who develop chronic AF. PMID- 11220537 TI - Determinants of development of permanent atrial fibrillation and its treatment. AB - We evaluated the rate of progression of permanent atrial fibrillation (AF) and identified clinical factors that predict this event in 63 consecutive patients who had undergone AV junctional ablation and DDDR pacemaker implantation for drug refractory paroxysmal atrial fibrillation/ flutter. Immediately after ablation, anti-arrhythmic drugs were discontinued in all cases. Permanent AF was considered to have developed if AF was present on two consecutive 6-monthly examinations with no interim documented sinus rhythm. During a mean follow-up of 23 +/- 16 months, 22 (35%) of the 63 patients developed permanent AF. The actuarial estimate of progression of permanent AF was 22%, 40% and 56%, respectively, 1, 2 and 3 years after ablation. Age and underlying heart disease were independent predictors of progression of permanent AF. Only one (6%) of 16 patients with idiopathic AF had permanent AF (low risk group). Among the 47 patients with structural heart disease, permanent AF developed in 18 (62%) of the 29 who were aged >75 years or had >12 arrhythmic episodes per year and a symptom duration >4 years (high risk group), but only in three (17%) of the remaining 18 patients who did not (intermediate risk group). In conclusion, during a 3-year follow-up period, about half of the patients with a history of drug-refractory paroxysmal AF did not develop permanent AF after AV junctional ablation and dual-chamber pacemaker implantation, even in the absence of anti-arrhythmic drug therapy. Moreover, subgroups of patients whose risk of permanent AF progression differed were identified on the basis of simple baseline clinical variables. The results of this study form the necessary background for the correct management of patients after AV junction ablation and for the planning of future trials in this field. PMID- 11220538 TI - The Atrial Pacing Peri-ablation for Paroxysmal Atrial Fibrillation (PA3) Study: rationale and study design. AB - The Canadian Atrial Pacing Peri-Ablation for Paroxysmal Atrial Fibrillation Study tested the hypotheses that atrial pacing prevents paroxysmal atrial fibrillation (PAF) in patients without symptomatic bradycardia and that DDDR pacing is more likely to prevent PAF following total atrioventricular (AV) node ablation compared to VDD pacing. Patients with PAF who were refractory to or intolerant of antiarrhythmic drug therapy received a Medtronic Thera DR pacemaker 3 months prior to a planned total AV node ablation. Patients were randomized to atrial pacing or no pacing therapy. The time to first recurrence of sustained PAF was the primary study outcome event. Following AV node ablation, patients were randomized to the DDDR or VDD mode in a crossover study design. Patients were followed in each mode for 6 months. The time course of PAF recurrence was compared for each pacing mode. PMID- 11220539 TI - Third-degree inter-atrial block and supraventricular tachyarrhythmias. PMID- 11220540 TI - Assessment of left ventricular pacing in patients with severe cardiac failure after atrioventricular node ablation and right ventricular pacing for permanent atrial fibrillation. PMID- 11220542 TI - Ablate and pace therapy for paroxysmal atrial fibrillation, too much too late. PMID- 11220541 TI - Mode switching in dual chamber pacemakers: effect of onset criteria on arrhythmia related symptoms. AB - AIMS: Various mode-switching algorithms are available with different tachyarrhythmia detection criteria to be satisfied to initiate mode-switching. This study evaluated three different mode-switching algorithms in patients with paroxysmal atrial fibrillation. METHODS AND RESULTS: Seventeen patients completed the study. Three mode-switching algorithms were downloaded as software into the pacemaker, each for 1 month in a single-blind, randomized sequence. The criteria to initiate mode-switching were: mean atrial rate ('standard'), '4-of-7' or '1-of 1' atrial intervals to exceed the atrial detection rate. Symptoms for each were measured using the Symptom Checklist Frequency and Severity index. The median number of mode-switch episodes increased from 20 for 'standard' to 39 for '4-of 7' (P=0.029 vs 'standard') and 103 for '1-of-1' (P=0.0012 vs 'standard') onset criteria. Median duration of episodes decreased from 2.5 min with 'standard' to 1.4 min with '4-of-7' and 0.4 min with '1-of-1' onset criteria. Frequency of symptoms was lower using '4-of-7' (18.2 +/- 12.0 vs 23 +/- 12.0, P=0.08) or '1-of 1' (20.4 +/- 12.4 vs 23 +/- 12.0, P=0.07) than 'standard' onset criteria. Severity of arrhythmia tended to be less with either '4-of-7' (16 +/- 10.4 vs 19.1 +/- 19.4, P=0.12) or '1-of-1' (17.5 +/- 10.3 vs 19.1 +/- 9.4, P=0.18) than with 'standard' onset criteria. CONCLUSIONS: The more sensitive onset criteria for detection of atrial tachyarrhythmias were associated with lower frequency and severity of symptoms. PMID- 11220543 TI - Assessment of accessory pathway and atrial refractoriness by transoesophageal and intracardiac atrial stimulation: an analysis of methodological agreement. AB - AIMS: Measurement of the refractory properties of asymptomatic overt accessory pathways is performed to assess the risk for significant arrhythmias. We hypothesized that a transoesophageal atrial stimulation (TAS) protocol would accurately predict simultaneously measured invasive intra cardiac stimulation (ICS) of the anterograde effective refractory period of the accessory pathway (AP ERP) METHODS AND RESULTS: Fourteen single pathway Wolff-Parkinson-White (WPW) syndrome patients underwent TAS during ICS and 24 h prior to it. The AP-ERP was measured using incremental atrial extra stimuli from TAS, the right atrium (RA) and the coronary sinus (CS) using drive trains of 500 and 600 ms. Stimulus latency was measured from intracardiac electrocardiograms. For methodological comparison, Altman-Bland analysis was used to create the limits of agreement (within-patient mean of differences +/- two standard deviations). There were no or small differences in the AP-ERP, as assessed by TAS, compared to RA and CS. Methodological disagreement between the three sites were common, however, and the limits of agreement ranged from +/- 30 to +/- 76 ms. The concordance between TAS and RA, with regards to the AP-ERP value of 270 ms, was 63% when measured as S1S2 and was 67% when measured as A1A2. The stimulation site delay was significantly shorter for TAS compared to RA and CS sites. The two TAS procedures performed a day apart, revealed a coefficient of variation of 9% and a coefficient of reproducibility of 63 ms. CONCLUSIONS: Despite adequate reproducibility, TAS fails to predict the AP-ERP by ICS. Differences in stimulus latency is responsible, in part, for the disagreement. Invasive ICS cannot be replaced by TAS for risk stratifying WPW patients. PMID- 11220544 TI - Clinical usefulness of head-up tilt test in patients with syncope and intraventricular conduction defect. AB - Head-up tilt test was performed in 99 patients with syncope of unknown origin and intraventricular conduction defect. Twenty-five per cent had a positive response to tilt with reproduction of spontaneous clinical symptoms. Holter recording revealed paroxysmal atrioventricular (AV) block in three patients. Carotid sinus massage was positive in four patients. An electrophysiological study was performed in 76 patients with abnormal findings in 17 (22%). Thus, vasovagal syncope was the discharge diagnosis in 25 patients (25%). Therefore, tilt test should be considered in patients with intraventricular conduction defect presenting with syncope of unknown origin, especially if clinical findings suggest the possibility of a vasovagal mechanism, or if the results of the electrophysiological study are inconclusive. PMID- 11220545 TI - SAFE PACE 2: Syncope and Falls in the Elderly--Pacing and Carotid Sinus Evaluation: a randomized controlled trial of cardiac pacing in older patients with falls and carotid sinus hypersensitivity. AB - SAFE PACE is a multicentre randomized controlled trial to assess the efficacy of dual-chamber pacing in older patients with carotid sinus hypersensitivity and recurrent unexplained falls. Patients are eligible if they have had two or more unexplained falls (+/- up to one syncope) and if they have a cardio-inhibitory response (>3 s asystole) to carotid sinus massage. Patients will be randomized to receive either a Medtronic Kappa 700(Europe)/Kappa 400(North America) pacemaker or an implantable loop recorder (ILR)(control group). Patients will be required to complete weekly fall diaries. The primary outcome measure is the number of patients who fall in the 24-month follow-up period. Recruitment began in October 1998 and continues for 12 months; the follow-up is for 24 months. PMID- 11220546 TI - Report of a study group on ablate and pace therapy for paroxysmal atrial fibrillation. Barcelona Discussion Group. Working Group on Arrhythmias of the European Society of Cardiology. AB - Atrioventricular junctional (AVJ) catheter ablation followed by pacemaker implantation is now widely accepted for patients affected by paroxysmal atrial fibrillation (PAF) not controlled by antiarrhythmic drugs. However, few data exist on its indications, optimal methodology and complications. Therefore a study group examined current practice in Europe and North America, using a questionnaire, followed by a Study Group Meeting to discuss the results. Based upon this, class I, class II and class III indications were proposed. Class I indications (for which general agreement existed) include drug-refractory PAF, correlating with important symptoms, the bradycardia tachycardia syndrome already treated with a pacemaker, and continued PAF. Large differences exist in the current methodology, but consensus was reached on the technical approaches of right and left-sided AVJ ablation, and on the timing of pacemaker implant in relation to ablation. No complete agreement was reached on technical features such as catheter choice and heparin use. The recommended pacing mode was DDDR with mode switching. PMID- 11220547 TI - Metabolic consequences of weight loss on glucose metabolism and insulin action in type 2 diabetes. PMID- 11220548 TI - Metformin and lactic acidosis in diabetic humans. PMID- 11220549 TI - Using dose-response characteristics of therapeutics agents for treatment decisions in type 2 diabetes. PMID- 11220550 TI - Cosegregation of obesity with familial aggregation of type 2 diabetes mellitus. AB - OBJECTIVE: We have shown that a positive family history of diabetes, and the variables of general and central obesity are independent risk factors for type 2 diabetes in our population. This study was done to evaluate whether a familial predisposition to diabetes resulted in a tendency for adverse anthropometric and haemodynamic profiles in south Indian non-diabetic subjects. METHODS: The analysis was carried out on 2463 subjects (M: F, 1196: 1267) with normal glucose tolerance (NGT). The study subjects were selected from population surveys for diabetes. Details of age, sex, family history of diabetes, body mass index (b.m.i.), waist-to-hip ratio (WHR) and blood pressure were recorded. Serum cholesterol and triglycerides were estimated. RESULTS: A positive family history of diabetes was present in 24.7% of our subjects. Mean b.m.i. and percentage of obesity were significantly higher in families with a positive family history (group 2) vs. families with no family history (group 1). Subjects in group 2 had a higher 2-h plasma glucose (p < 0.001) and higher prevalence of hypertension (chi2 = 6.91, p = 0.0086). Factor analysis with principle components analysis (PCA) showed that a family history of diabetes clustered with WHR in men, and with b.m.i. and WHR in women. The b.m.i. formed a different domain with blood pressure in both sexes. WHR and b.m.i. clustered with cholesterol and triglycerides in another domain. CONCLUSIONS: In this population, general and central obesity are associated with a family history of diabetes. A family history of diabetes may increase the risk of hypertension and hyperlipidaemia indirectly through its connection with b.m.i. PMID- 11220551 TI - Lipid lowering explains the insulin sensitivity enhancing effects of a thiazolidinedione, 5-(4-(2-(2-phenyl-4-oxazolyl)ethoxy)benzyl)-2,4 thiazolidinedione. AB - AIM: Insulin resistance is a characteristic feature of type 2 diabetes and obesity. The present study examined the effects of TZD300512, a thiazolidinedione, on glucose and lipid metabolism in the fatty Zucker rat (fa/fa), a rat model of insulin resistance. METHODS: TZD300512 was administered (2.0 mg/kg/day) in the diet for 1 week to chronically catheterized Zucker fa/fa rats. We measured triglyceride clearance rate and hepatic triglyceride output. We assessed baseline glucose metabolism, and insulin-mediated glucose uptake. We also determined whether the insulin sensitivity enhancing effects of TZD300512 could be reversed by infusion of Intralipid. RESULTS: TZD300512 treatment markedly reduced fasting plasma triglyceride by 72% and nonesterified free fatty acids by 46%. Moreover, treatment significantly enhanced plasma triglyceride clearance (AUC; 60.36+/-11.50 v 131.44+/-18.45 mM/min), but hepatic triglyceride output was not altered. Drug treatment significantly reduced fasting plasma glucose by 25%, plasma insulin by 73%, and had no effect on glucagon levels. Glucose infusion rate (GIR) needed to maintain euglycemia during hyperinsulinemic clamp was significantly increased from 34.96+/-3.94 micromol/kg/min to 123.80+/ 4.80 micromol/kg/min, while whole body glucose uptake was more than doubled (58.49+/-2.86 control vs. 126.97+/-3.8 treated micromol/kg/min). Insulin-induced suppression of hepatic glucose production was nearly complete with treatment. Intralipid infusion reversed drug-induced improvement in insulin sensitivity. CONCLUSIONS: These results suggest that TZD300512-favourable alterations in lipid metabolism have a significant impact on its effectiveness in enhancing insulin sensitivity in a severely insulin resistant rodent model of type 2 diabetes. PMID- 11220552 TI - Diabetes-induced biochemical changes in rat lens: attenuation of cataractogenesis by pyruvate. AB - AIM: Studies have been conducted to determine the effect of pyruvate administration on the biochemistry of rat lens and the status of its transparency as affected by diabetic conditions. METHODS: Sprague-Dawley rats were rendered diabetic by intravenous (i.v.) injection of streptozotocin (55 mg/kg body weight (b.w.)) and treated with sodium pyruvate (2%) in drinking water. The levels of glucose, fructose, sorbitol, ATP, GSH, MDA as well as glycated proteins in the lenses were determined at various intervals after the onset of diabetes and the values compared with untreated diabetic controls. The progress of cataract formation and associated histological changes in the tissue were also monitored. RESULTS: Studies show that the pyruvate treatment decreased the extent of several biochemical changes known to be associated with cataract formation, such as the elevation in the levels of glycated proteins, sorbitol, lipid peroxidation (MDA) and inhibition of the cation pump. The progress of cataract was also significantly delayed. CONCLUSION: Exogenous administration of this compound hence was found to exert an overall protective effect against cataract formation induced by the diabetic conditions. PMID- 11220553 TI - Weight loss with sibutramine improves glycaemic control and other metabolic parameters in obese patients with type 2 diabetes mellitus. AB - AIM: To determine the efficacy and tolerability of sibutramine hydrochloride in obese patients whose type 2 diabetes was poorly controlled on diet alone or with an oral antidiabetic agent. METHODS: This study was a 24-week, double-blind, multicentre trial following a 5-week placebo run-in period. One hundred and seventy-five obese (body mass index (b.m.i.) > or =27 kg/m2) patients with poorly controlled type 2 diabetes mellitus were randomized either to sibutramine (n = 89; mean age 53.5 years; mean weight 99.3 kg) or placebo (n = 86; mean age 55 years; mean weight 98.2 kg) at 16 participating centres. To achieve moderate calorie restriction (deficit > or = 250-500 kcal/day), individual dietary counselling was accompanied by either placebo or sibutramine (initial dosage of 5 mg/day titrated up by 5 mg biweekly through week 6, and maintained at 20 mg through week 24). The main outcome measures included changes in weight, b.m.i., waist and hip circumference, glycaemic control, lipid profile, and quality of life, and evaluation of reported adverse events. RESULTS: Sixty-seven per cent of sibutramine patients and 71% of placebo patients completed the study. At week 24 when comparing those who completed the course, sibutramine compared with placebo patients showed significantly greater (p < 0.001) absolute (-4.3 vs. -0.4 kg) and percentage (-4.5% vs. -0.5%) weight loss. Weight loss > or =5% or 10% was achieved by 33% and 8% of sibutramine patients, respectively, but no placebo patients (p < 0.03 or better). Improvement in glycaemic control was correlated with weight loss (p < 0.001). In 5% and 10% weight-loss responders, mean treatment differences were -0.53% and -1.65% (p < or = 0.05), respectively, for HbA1c, and -1.4 mmol/l (p < or =0.05) and -3.8 (p < or =0.05) mmol/l for fasting plasma glucose. Sibutramine patients also showed improvements in fasting insulin, triglycerides, HDL cholesterol, and quality-of-life assessments. Overall, sibutramine was well tolerated compared with the placebo. Sibutramine treatment was associated with small mean increases in blood pressure (BP) and pulse, although an increase in BP was not seen in sibutramine-treated patients who lost > or = 5% of their weight. CONCLUSIONS: Sibutramine produced statistically and clinically significant weight loss when used in combination with recommendations for moderate caloric restriction. This weight loss was associated with improvements in metabolic control and quality of life, and sibutramine was generally well tolerated in obese patients with type 2 diabetes. PMID- 11220554 TI - Troglitazone reduces plasma levels of tumour necrosis factor-alpha in obese patients with type 2 diabetes. AB - We evaluated the effect of troglitazone (given orally 400 mg/day) on glucose intolerance and on the plasma levels of tumour necrosis factor-alpha (TNF-alpha) in 12 obese patients with type 2 diabetes for 12 weeks. Troglitazone significantly decreased fasting plasma glucose, serum C-peptide, serum insulin and HbA1c levels. Plasma levels of TNF-alpha were significantly reduced by troglitazone administered for 8 and 12 weeks. Troglitazone administration significantly improved insulin resistance, but did not affect pancreatic beta cell function as evaluated by the homeostasis model assessment (HOMA). In the present study, we reported for the first time that troglitazone administration significantly reduces plasma levels of TNF-alpha in obese patients with type 2 diabetes. PMID- 11220555 TI - Is rate response superior to single rate pacing in atrial arrhythmia control? PMID- 11220556 TI - Positive head-up tilt table test in patients with the long QT syndrome. AB - AIMS: Syncope in patients with the long QT syndrome is commonly attributed to a ventricular arrhythmia (torsades de pointes). The susceptibility of patients with the long QT syndrome (LQTS) to neurally mediated syncope is currently unknown. METHODS AND RESULTS: Head-up tilt table testing (70 degrees) was performed in six patients with the long QT syndrome and a history of syncope. All patients had syncope with a mixed response. The RR interval was significantly decreased 2 min before the onset of syncope (980 +/- 125 ms vs 630 +/- 91 ms, P=0.003), and significantly increased during syncope (983.17 +/- 224.71; P=0.006). Non significant changes in QT intervals were observed. Baseline QT was 513 +/- 86 ms and decreased to 450 +/- 59 ms 2 min before the onset of syncope (P=0.11). Although not statistically significant, QT intervals during syncope were longer than at 2 min before syncope (485 +/- 85 ms vs 450 +/- 59 ms; P=0.29). CONCLUSION: Our results suggest that patients with the LQTS are susceptible to neurally mediated syncope. Whether this susceptibility differs from control populations remains unresolved. From a clinical standpoint, neurocardiogenic syncope should be considered a diagnostic alternative in patients with LQTS. PMID- 11220557 TI - Unravelling the mechanisms of symptoms in patients at risk of genetically determined cardiac arrhythmias. PMID- 11220558 TI - Antiarrhythmic benefits of dual chamber stimulation with rate-response in patients with paroxysmal atrial fibrillation and chronotropic incompetence: a prospective, multicentre study. AB - BACKGROUND: While the haemodynamic benefits of DDDR pacing compared with DDD pacing in patients with brady-tachy syndrome and chronotropic incompetence (CI) are well demonstrated, the antiarrhythmic advantage is controversial and so far not clearly demonstrated. AIM: We have performed a prospective, randomized, multicentre study to evaluate the efficacy of DDDR and DDD pacing modes in preventing paroxysmal atrial fibrillation (PAF) episodes in patients with brady tachy syndrome and CI. METHODS AND RESULTS: Seventy-eight patients were included in the study. All patients had a dual chamber pacemaker implanted and were randomly programmed to DDD or DDDR with a cross over (DDD --> DDDR or vice versa) at 3 months. The final evaluation was performed at 6 months by means of two self administered symptom questionnaires to evaluate activity. Symptoms of palpitations were analysed and scored. The patients were less symptomatic with the DDDR mode. The number of mode-switch activations compared with symptomatic episodes of PAF confirmed the high rate of asymptomatic PAF episodes in patients with brady-tachy syndrome. We conclude that in a small but well defined population of patients affected by sick sinus syndrome with CI and severely symptomatic PAF, DDDR pacing compared with DDD pacing may offer an additional antiarrhythmic benefit and should be considered the primary mode of pacing. PMID- 11220559 TI - An epidemiological study of symptomatic paroxysmal atrial fibrillation in northwest Greece. AB - AIM: Although atrial fibrillation (AF) is the most commonly sustained arrhythmia, information about its incidence in the general population is sparse. Even more sparse is information on an important variety of AF, paroxysmal AF. The aim of this study is to assess the frequency of new cases of symptomatic paroxysmal AF per year ('incidence') in a general unselected population and to compare other epidemiological features with chronic AF patients. METHODS AND RESULTS: Over a 4 year period, we conducted a prospective, population-based survey of cases of AF in a defined geographical area with a known population size stratified for age and sex. Sources of identification were the two hospitals which serve the area and all the primary care settings. Patients with AF of less than 7 days duration were characterized as paroxysmal AF and all others as chronic AF. During the study period we identified 1551 patients with chronic AF (51.7% male, mean age 71 +/- 10.4 years and 48.3% females, mean age 73.1 +/- 10.8 years) and 443 patients with paroxysmal AF (59.6% male, mean age 59.6 +/- 13.3 years and 40.4% female, mean age 65.2 +/- 10.1 years). There was no underlying cardiovascular disease in 15.6% and 32.3% of patients with chronic and paroxysmal AF, respectively. The mean annual occurrence of new cases of paroxysmal AF was 6.2/10,000/year, and was higher (P<0.01) for men (7.2/10,000/year) than for women (5.3/10,000/year). The frequency of new paroxysmal AF cases rises with age, reaching a peak at 70-79 years and then declines. CONCLUSIONS: We conclude that paroxysmal AF is a relatively common arrhythmia, the occurrence of which increases with age and is more frequent in younger men than in women. Patients with chronic AF are older and more often have underlying heart and other disease than patients with paroxysmal AF. PMID- 11220561 TI - Incidence and clinical significance of transformation of atrial fibrillation to atrial flutter in patients undergoing long-term antiarrhythmic drug treatment. AB - AIMS: To investigate the rate of transformation of atrial fibrillation to atrial flutter in patients taking antiarrhythmic drugs for the prophylaxis of atrial fibrillation, we retrospectively analysed data from 305 consecutive patients with paroxysmal atrial fibrillation (155 male; mean age 63 +/- 11 years) treated with ventricular rate controlling drugs, antiarrhythmic drugs, or without drugs. METHODS AND RESULTS: At a mean follow-up of 9 months (range 1-24) all patients experienced recurrence of arrhythmia: 48 (14.6%, Group A) suffered Type 1 atrial flutter, and 257 (85.4%, Group B) atrial fibrillation. The relative rate of recurrence of atrial flutter vs atrial fibrillation was similar in patients without treatment or with ventricular rate controlling drugs (from 6.8% to 14.6%, P=ns). However, recurrence was higher (25%) in patients administered antiarrhythmic drug therapy. The relative risk in these patients was 3.02 times greater, compared with patients without treatment, or treated with rate controlling drugs (P<0.001). There were no differences between groups concerning the baseline clinical characteristics and the clinical consequences of the recurrence; patients with atrial flutter had a lower rate of conversion to sinus rhythm (42% vs 64%) and a higher rate of hospital admission (69% vs 36%) compared with those with atrial fibrillation. Six patients (8.5%) experienced 1:1 atrioventricular conduction during atrial flutter with a ventricular rate of 240 280 beats x min(-1). CONCLUSION: Our data suggest that the use of antiarrhythmic drugs for the prophylaxis of atrial fibrillation is associated with a threefold increase in the probability of Type 1 atrial flutter recurrence, as opposed to atrial fibrillation, which may have important clinical consequences, but which did not in our study. PMID- 11220560 TI - Attenuation of electrical remodelling in chronic atrial fibrillation following oral treatment with verapamil. AB - AIMS: Electrical remodelling with shortening of the atrial refractory period and increased fibrillatory rate occurs after onset of atrial fibrillation and can be attenuated by pre-treatment with intravenous verapamil. The aim of the present study was to investigate whether already established fibrillatory-induced shortening of atrial fibrillatory cycle length could be reversed with oral verapamil. METHODS AND RESULTS: Thirteen patients (nine men; mean age 67 years) with chronic atrial fibrillation (CAF) were studied. The dominant atrial cycle length (DACL) was estimated non-invasively using the frequency analysis of fibrillatory ECG (FAF-ECG) method. Measurements were repeated following treatment with slow release oral verapamil. DACL increased from 147 +/- 13 ms to 156 +/- 21 ms after 1 day (P=0.02), to 164 +/- 18 ms after 5 days (P=0.005) and finally to 160 +/- 16 ms after 6 weeks (P=0.008). CONCLUSION: Long-term oral treatment with verapamil increases the DACL significantly in patients with CAF. The prolongation is evident after 1 day and is further developed during the first 5 days of treatment. Since DACL is believed to be an index of refractoriness, the findings of the present study suggest that this treatment increases the atrial refractory period in patients with CAF. PMID- 11220563 TI - Impaired arterial baroreceptor sensitivity before tilt-induced syncope. AB - Autonomic dysfunction seems to play a central role in the pathophysiology of neurocardiogenic syncope (NCS) but conflicting data have recently become available. We evaluated autonomic nervous system (ANS) function (heart rate variability (HRV), systolic blood pressure variability (SBPV) and baroreceptor gain (BRG)) and non-invasive haemodynamics (cardiac output and total peripheral resistance) in patients with neurocardiogenic syncope. Retrospectively, we evaluated 12 NCS patients (positive head-up tilt without pharmacological provocation) in the basal state and at initial tilt, 12 non-NCS patients with tilt-negative syncope and 12 aged-matched normal controls. Prospectively, we evaluated 16 NCS patients to analyse the haemodynamics and ANS activity throughout the tilt test (beginning of tilt and before syncope occurs). HRV and SBPV were accessed by fast Fourier transforms (FFT) and spontaneous BRG by temporal sequences, slope and a index. Modelflow was used to quantify the non invasive haemodynamics. None of the autonomic and haemodynamic parameters at baseline or in the first 10 min of tilt was different among the respective NCS, non-NCS syncope and normal control groups, except for SBP, which was higher at baseline in controls. Throughout the tilt test in the prospective NCS group, the heart rate increased (88-95 beats x min(-1), P<0.05), systolic blood pressure decreased (123-109 mmHg, P<0.01), and arterial baroreceptor gain was reduced (7.6 to 5.5 ms mmHg(-1), P<0.01) and the absolute high frequency component of HRV (HF HRV) decreased (150-80 ms(-2), P<0.05), before syncope occurred. There was no change in the low frequency component of HRV (LF HRV), SBPV, cardiac output (CO) or total peripheral resistance (TPR). Tilt-induced syncope could not be predicted by non-invasive haemodynamic or autonomic parameters at rest or in the initial minutes of tilt. The decrease in arterial baroreceptor gain could be a precocious expression of the transient autonomic dysfunction that characterizes the occurrence of neurocardiogenic syncope. PMID- 11220562 TI - Effect of cardiac exposure by median sternotomy on atrial fibrillation cycle length. AB - BACKGROUND: Epicardial mapping is a powerful tool that has enabled us to gain insight into the electrical phenomena perpetuating atrial fibrillation and has guided the design of surgical and catheter-based therapeutic strategies. However, epicardial data are acquired during abnormal physiological conditions; the patients are anaesthetized, their chests opened, dislocating the heart and exposing it to air of room temperature, and the autonomic tone is modulated due to the surgery. The effect of intra-operative conditions on atrial electrophysiological properties have not been investigated before. Thus in the present study we assessed the atrial cycle length, shown to be an index of atrial refractoriness, and the ventricular rate before and during open-heart surgery in 10 patients with chronic atrial fibrillation and an underlying heart disease. METHODS AND RESULTS: Using a newly introduced and validated ECG method known as frequency analysis of fibrillatory ECG (FAF-ECG), the atrial cycle length and the ventricular rate were determined just before surgery. After anaesthesia and median sternotomy, epicardial mapping of the entire right atrial free wall was performed. The mean ventricular rate as well as the dominant atrial fibrillation cycle length consistently increased, the former from 71 to 92 beats x min(-1) (mean of all patients, P<0.05) and the latter from 156 to 172 ms (P<0.05). CONCLUSIONS: Atrial fibrillation cycle length, an index of atrial refractoriness, is increased as an effect of anaesthesia and heart exposure during open-heart surgery in patients with chronic atrial fibrillation, implying that atrial activation might be altered, which must be considered when interpreting data from epicardial conduction analysis. PMID- 11220564 TI - An abdominal active can defibrillator may facilitate a successful generator change when a lead failure is present. AB - AIMS: Defibrillator generator changes are frequently performed on patients with an implantable cardioverter defibrillator in an abdominal pocket. These patients usually have epicardial patches or older endocardial lead systems. At the time of a defibrillator generator change defibrillation may be unsuccessful as a result of lead failure. We tested the hypothesis that an active can defibrillator implanted in the abdominal pocket could replace a non-functioning endocardial lead or epicardial patch. METHODS AND RESULTS: An abdominal defibrillator generator change was performed in 10 patients, (mean age = 67 +/- 13 years, nine men). Initially, a defibrillation threshold (DFT) was obtained using a passive defibrillator and the chronic endocardial or epicardial lead system. DFTs were then performed using an active can emulator and one chronic lead to simulate endocardial or epicardial lead failure. We tested 30 lead configurations (nine endocardial and 21 epicardial). Although a DFT of 7.3 +/- 4.2 joules was obtained with the intact chronic lead system, the active can emulator and one endocardial or epicardial lead still yielded an acceptable DFT of 19.9 +/- 6.1 joules. In addition, a successful implant (DFT < or = 24 joules) could have been accomplished in 28 of 30 (93%) lead configurations. CONCLUSION: An active can defibrillator in an abdominal pocket may allow for a successful generator change in patients with defibrillator lead malfunction. This would be simpler than abandoning the abdominal implant and moving to a new pectoral device and lead or tunnelling a new endocardial electrode. However, loss of defibrillation capability with a particular complex lead may be a warning of impending loss of other functions (eg. sensing and/or pacing). PMID- 11220565 TI - Multiple hardware complications in a patient with an ICD. AB - Hardware-related complications in implantable cardioverter/defibrillators (ICD) are still a common problem. Identifying underlying reasons becomes more and more difficult as the complexity of ICD systems increases. We report a patient with a dual chamber ICD (DDD-ICD) who suffered multiple complications. These included: ventricular oversensing causing inappropriate shocks and episodes of asystole; an insulation defect resulting in ineffective shocks as a consequence of a short circuit between the active can device and a defective high voltage cable; and device dysfunction requiring several hospitalizations and operative system revisions. PMID- 11220566 TI - Atrial flutter in the recipient atrium induced by premature beats arising from the donor atrium 10 years after orthotopic heart transplantation. AB - BACKGROUND: Several mechanisms for the genesis of supraventricular arrhythmias in patients after orthotopic heart transplantation have been reported. METHODS AND RESULTS: We describe a 58-year-old male patient in whom atrial flutter occurred 10 years after orthotopic heart transplantation. During an electrophysiological study, bidirectional conduction between the recipient and donor atria was found. Atrial flutter in the recipient atrium was induced by programmed stimulation of the donor atrium using a single extrastimulus. The clinical symptoms were caused by atrial flutter arising from the recipient atrium with 1:1 to 3:1 conduction to the donor atrium. Mapping the anastomosis between the two atria indicated fragmented potentials at a discrete site of conduction. Delivery of radiofrequency energy at this site terminated conduction in both directions. Subsequent atrial pacing of the donor and recipient atria, respectively, demonstrated bidirectional conduction block. CONCLUSION: Symptomatic arrhythmias in patients after heart transplantation can indirectly originate from the donor atrium via bidirectional recipient-donor atrial conduction. This type of arrhythmia can be successfully treated with radiofrequency ablation. PMID- 11220567 TI - Rare association of hypertrophic cardiomyopathy and complete atrioventricular block with prompt disappearance of outflow gradient after DDD pacing. AB - Although arrhythmias are common in hypertrophic cardiomyopathy (HCM), complete atrioventricular (AV) block is very unusual. A 27-year-old female presented with a recent history of syncope and exercise intolerance. ECG demonstrated complete AV block. Two-dimensional Doppler echocardiography revealed HCM with a 60 mmHg left ventricular outflow tract (LVOT) gradient. A temporary transvenous ventricular pacemaker was inserted urgently, and subsequently replaced by a permanent DDD pacemaker. All symptoms were eliminated. This symptomatic improvement was associated with complete disappearance of LVOT gradient at the time of implantation. No gradient was observed during early follow-up and at 6 months after DDD pacemaker implantation. PMID- 11220568 TI - Slow pathway ablation in a patient with common AV nodal reentrant tachycardia and complete situs inversus. AB - A 72-year-old woman with complete situs inversus underwent successful slow pathway ablation of typical AV nodal reentrant tachycardia. Catheter ablation of AV nodal reentrant tachycardia in dextrocardia required a lengthy procedure but was safe and without complications. PMID- 11220569 TI - Experimental setup for the determination of analytes contained in ultrasonically levitated drops. AB - An automated technique for the determination of analytes in an ultrasonically levitated sample of 2 to 5 microL volume has been developed. Contactless dosing of reagents or solvents into an ultrasonically levitated drop was realized via piezoelectric micropumps. Drop size was continually controlled with a programmed CCD camera. A diode array spectrometer designed for the use with optical fibers was used for absorption and fluorescence measurements. Determinations via direct absorption measurements following the method of standard addition and acid-base titrations with an absorption indicator and a fluorescent indicator were carried out. The mean consumption of sodium hydroxide added via a piezoelectric micropump in five successive titrations with 18 nmol of sulfuric acid inside a levitated drop (indicator bromothymol blue) had a relative standard deviation of 0.7% and differed only by 0.2% from the expected value. PMID- 11220570 TI - Non-invasive identification of chemical compounds by energy dispersive X-ray fluorescence spectrometry, combined with chemometric methods of data evaluation. AB - Chemicals from customers' returns have to be analyzed before they can be reused as raw materials in production. A procedure for non-invasive qualitative analysis of compounds in a closed container based on energy dispersive X-ray fluorescence (EDXRF) spectrometry is described. EDXRF was chosen as method for noninvasive analysis of chemicals through PE bottle walls without opening the bottle. This analysis aims for a quick proof of correspondence between the declaration of a reagent on the label of the bottle and its content. This analytical result cannot be achieved by a mere evaluation of characteristic element lines in EDXRF-spectra in combination with the method of matrix correction or the method of mean atomic number. These methods take into account only a small part of the total information available in an X-ray spectrum. It is shown here that valuable additional information is extractable from the spectral ranges of the Compton scattering and Rayleigh-scattering areas by the use of methods of multivariate data analysis, especially by principle component analysis (PCA). Regularized discriminant analysis (RDA) was employed to establish a classification scheme for unknown samples. PMID- 11220571 TI - Kinetics and stoichiometry in the Karl Fischer solution. AB - The mechanisms of the Karl Fischer (K.F.) reaction are reviewed and further investigated. Both kinetic measurements of the iodine concentration and chromatographic determinations of the reaction products were performed. In alcoholic solutions mainly alkyl sulfite is oxidized, and a reaction via partial formation of sulfur trioxide is proposed. In methanol an exact 1:1 stoichiometry (H2O:I2) has been verified. In the aprotic, dipolar solvents acetonitrile, DMF and propylene carbonate HSO3- is oxidized by iodine. Based on formation and subsequent hydrolysis of base - SO3 adducts the stoichiometric factor for water is determined by type and concentration of the base, by the concentration of water and by the solvent itself. - In K.F. reagents the oxidation of SO2 by aerial oxygen to sulfate and alkyl sulfate takes place as a side reaction. PMID- 11220572 TI - Comparative performance study of ICP mass spectrometers by means of U "isotopic measurements". AB - The performance of four commercially available ICPMS instruments of three different types was compared by means of uranium "isotopic measurements". Examined were two quadrupole sector (different generation, different manufacturer), one single detector double focusing magnetic sector and one multiple collector double focusing magnetic sector instruments. The same samples of the IRMM-072 series were used under routine conditions to measure the 233U/235U and the 233U/238U ratios which, in these samples, vary over almost three orders of magnitude from approximately 1 to approximately 2 x 10(-3). Within expanded (k = 2) uncertainties, good agreement was observed between the certified values and the data internally corrected for mass-discrimination effects. The magnitude of the evaluated uncertainties was different for each type of instrument. With the multiple collector instrument, expanded uncertainties varied from +/- 0.04% to +/- 0.24% for the 233U/235U ratio, and from +/- 0.08% to +/- 0.27% for the 233U/238U ratio. They were approximately 1 to 5 times larger with the single detector magnetic sector instrument, and approximately 10 to 25 times larger with both quadrupole sector instruments. With the multiple collector instrument, repeatability of the measurements seemed to be limited by the difficulty of correcting properly for instrumental background, whereas with the single detector magnetic sector instrument the counting statistics was the only limitation (on smallest ratios). Apparent mass-discrimination was clearly found to be larger but more reproducible (and hence easier to correct for) in the case of magnetic sector instruments than for both quadrupole sector instruments. If space charge effects were the main source of mass-discrimination for all instruments, these results are in contradiction with the hypothesis of the size of mass-discrimination decreasing with the acceleration voltage. With the single detector magnetic sector instrument in particular (when operated by changing the ion energy only), our results pointed at more than only one major source of mass discrimination, with variable size depending on the ratios measured. PMID- 11220573 TI - Noise power spectra and recovery rates obtained with different nebulizer systems in ICP atomic emission spectrometric analyses in the case of different types of salts and salt contents. AB - The features of different nebulizer systems (cross-flow-, Meinhard- and GMK system) in the ICP atomic emission spectrometric analyses of solutions with different contents of different salts were evaluated. As basis for the comparison of the nebulizer systems the recovery rates and noise power spectra were used. Both showed that the GMK-system could be used for the widest diversity of salts (sodium chloride, ammonium sulfate and sodium tetraborate) and concentration range (0-10%, (m/v)) followed by the cross-flow-system and the Meinhard-system in ICP-OES using a 1 kW argon ICP. Of all nebulizer systems the nebulizer according to Meinhard has the lowest performance for the salts investigated. The noise power spectra of all nebulizer systems are dominated by interference noise from the sample introduction system. This noise increases with the salt concentration of the solution and the GMK-system shows the lowest increase, followed by the cross-flow- and Meinhard-system. PMID- 11220574 TI - Determination of arsenic by inductively coupled plasma mass spectrometry- comparison of sample introduction techniques. AB - A comparison is made of four sample introduction techniques for the determination of As by inductively coupled plasma mass spectrometry. The techniques studied were 1) flow injection with pneumatic nebulization (FIA-PN), 2) direct electrothermal vaporization (ETV), 3) continuous hydride generation (HG) and 4) hydride generation with in situ trapping followed by electrothermal vaporization (HG-ETV). It was found that FIA-PN and ETV gave similar detection limits in concentration units (about 20 pg mL(-1)), although ETV had a much lower absolute detection limit (0.2 pg). Sample introduction by hydride generation gave an inferior detection limit (100-200 pg mL(-1)), also in combination with in situ trapping and ETV, owing to the blank signal from traces of As in NaBH4 which is difficult to eliminate. The results indicate that the more elaborate sample introduction techniques based on ETV and HG may not offer significant advantages compared to normal solution nebulization for the determination of As in simple sample matrices such as natural fresh waters, where matrix removal is not required. PMID- 11220575 TI - Improvement of the model for calculation of relative sensitivity coefficients in inductively coupled plasma mass spectrometry. AB - Relative sensitivity coefficients (RSCs) were determined for 68 elements in inductively coupled plasma mass spectrometry (ICP-MS). It was shown that the Saha equation gives a rough description of ionization processes in ICP. A dependence of RSCs on the absolute electronegativity of atoms was found. This parameter is substantially affecting the accuracy of RSCs calculation for chemically active elements. Taking into account absolute electronegativities of the atoms for the calculation of RSCs, the ion formation processes in ICP-MS could be better described than by using first ionization potentials. The mean relative systematic error of RSCs calculation using absolute electronegativity was improved to 0.30. PMID- 11220576 TI - A new strategy of solution calibration in laser ablation inductively coupled plasma mass spectrometry for multielement trace analysis of geological samples. AB - Because multielement trace analysis by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) is often limited by the lack of suitable reference materials with a similar matrix composition, a novel quantification strategy using solution calibration was developed. For mass spectrometric multielement determination in geological samples a quadrupole-based LA-ICP-MS is coupled with an ultrasonic nebulizer (USN). In order to arrange matrix matching the standard solutions are nebulized with a USN during solution calibration and simultaneously a blank target (e.g. lithium borate) is ablated with a focused laser beam. The homogeneous geological samples were measured using the same experimental arrangement where a 2% nitric acid is simultaneously nebulized with the USN. Homogeneous targets were prepared from inhomogeneous geological samples by powdering, homogenizing and fusing with a lithium borate mixture in a muffle furnace at 1050 degrees C. Furthermore, a homogeneous geological glass was also investigated. The quantification of analytical results was performed by external calibration using calibration curves measured on standard solutions. In order to compare two different approaches for the quantification of analytical results in LA-ICP-MS, measured concentrations in homogeneous geological targets were also corrected with relative sensitivity coefficients (RSCs) determined using one standard solution only. The analytical results of LA-ICP-MS on various geological samples are in good agreement with the reference values and the results of other trace analytical methods. The relative standard deviation (RSD) for trace element determination (N = 6) is between 2 and 10%. PMID- 11220577 TI - Detection of heavy metals in water by fluorescence spectroscopy: on the way to a suitable sensor system. AB - In order to develop a fiber optical heavy metal ion detection system, the applicability of selected complexing agents with fluorescent properties has been studied. Beginning with the application of known chelators, like BTC-5N, Newport Green, neocuproine, and chromotropic acid, a sensor configuration has been found, which allows the detection of Cd2+, Ni2+, and Cu2+ well below the chemical parameter threshold values of the new Water Quality Directive 98/83/EU. The sensor itself uses a membrane separation of the chelator flow from the sample volume. The diffusion across the membrane limits the response time to about 15 to 20 min. Applications are seen in monitoring networks. PMID- 11220578 TI - Dyeless optical detection of ammonia in the gaseous phase using a pH-responsive polymer--characterization of the sorption process. AB - pH-responsive polymers enable the dyeless optical detection of acidic or basic pollutants in air. The characterization of the sorption process and the optimization of the response time of the sensitive layers were high-lighted. The swelling of a pH-responsive polysiloxane induced by sorption of gaseous ammonia was investigated by measurement techniques such as spectroscopic ellipsometry (SE) and infrared spectroscopy (IR). Furthermore, the pH-responsive polymer was applied for the detection of gaseous ammonia using the LED-based reflectometric interference spectroscopy set-up (RIfS4lambda). A limit of detection of 0.30 mg/m3 ammonia and a response time (t90%) of 35 s could be verified. The application of pH-responsive polymers can be a powerful alternative to dye-based optical sensing, since photobleaching or leaching of the sensitive functional unit cannot occur applying this approach, and since the properties of the sensitive layer proved to be very promising. PMID- 11220579 TI - Optical sensor for seawater salinity. AB - An optical sensor for the measurement of salinity in seawater has been developed. It is based on a chloride-quenchable fluorescent probe (lucigenin) immobilized on a Nafion film. Two approaches for measuring salinity via chloride concentration are presented. In the first, a change in salinity corresponds to a change in the fluorescence intensity of lucigenin. In the second, the fluorescence intensity information is converted into a phase angle information by adding an inert phosphorescent reference luminophore (a ruthenium complex entrapped in poly(acrylonitrile) beads). Under these conditions, the chloride-dependent fluorescence intensity of lucigenin can be converted into a chloride-dependent fluorescence phase shift which serves as the analytical information. This scheme is referred to as dual lifetime referencing (DLR). The sensor was used to determine the salinity in seawater and brackish water of the North Sea. PMID- 11220580 TI - Novel teststrip with increased accuracy. AB - A new type of a simple and cheap teststrip for liquid samples is described. It is based on microchromatography or microtitration on a porous, capillary-active substrate (e.g., filter paper or a similar absorbent material). In case of microchromatography an analyte-selective indicator (and other auxiliary reagents) is impregnated or immobilized on the capillary-active substrate; in case of micro titration the capillary-active substrate contains a titrant which reacts stoichiometrically with the analyte. Quantitative analysis is performed by measurement of an area (which had changed its color) rather than by evaluation of the shade or intensity of a color (like in conventional teststrips). In order to show the broad applicability of this new principle teststrips for different analytes like Quaternary Ammonium Compounds (QACs), the cation Ni2+, the anion SO4(2-) and H2O2 are described. The detection limit and working range of the novel teststrip can be adjusted by variation of its size. PMID- 11220581 TI - Sulfur speciation by capillary zone electrophoresis: conditions for sulfite stabilization and determination in the presence of sulfate, thiosulfate and peroxodisulfate. AB - Capillary zone electrophoresis (CZE) was used for the separation of the sulfur species SO3(2-), SO4(2-), S2O(3-) and S2O8(2-). Using an electrolyte system with 9.5 mmol L(-1) potassium chromate as UV-absorbing probe and 1 mmol L(-1) diethylenetriamine (DETA) as electroosmotic flow modifier, various possibilities for the stabilization of sulfite and electrophoretic separation of the sulfur anions were investigated. By adding 5% propanol as a stabilizer to both the working electrolyte and the sample solution, a good stabilization for sulfite and a separation of the sulfur anions in a short analysis time (4 min) was achieved. The advantages by using propanol instead of other stabilizers often used in analytical techniques are discussed. The electrophoretic separation of the sulfur anions was optimized with respect to the pH of the working electrolyte and concentration of the electroosmotic flow modifier (DETA). The detection limits achieved for SO3(2-), SO4(2-), S2O3(2-) and S2O8(2-) were 0.35, 0.25, 0.78 and 0.80 mg L(-1), respectively. PMID- 11220583 TI - Depth profile analysis of various titanium based coatings on steel and tungsten carbide using laser ablation inductively coupled plasma--"time of flight" mass spectrometry. AB - A homogenized 193 nm ArF* laser ablation system coupled to an inductively coupled plasma-"Time of Flight"-mass spectrometer (LA-ICP-TOFMS) was tested for depth profiling analysis on different single-layer Ti based coatings on steel and W carbides. Laser parameters, such as repetition rate, pulse energy and spatial resolution were tested to allow optimum depth related calibration curves. The ablation process using a laser repetition rate of 3 Hz, 120 microm crater diameter, and 100 mJ output energy, leads to linear calibration curves independent of the drill time or peak area used for calibrating the thickness of the layer. The best depth resolution obtained (without beam splitter) was 0.20 microm per laser shot. The time resolution of the ICP-TOFMS of 102 ms integration time per isotope was sufficient for the determination of the drill time of the laser through the coatings into the matrix with better than 2.6% RSD (about 7 microm coating thickness, n = 7). Variation of the volume of the ablation cell was not influencing the depth resolution, which suggests that the depth resolution is governed by the ablation process. However, the application on the Ti(N,C) based single layer shows the potential of LA-ICP-TOFMS as a complementary technique for fast depth determinations on various coatings in the low to medium microm region. PMID- 11220582 TI - Stability studies of arsenic, selenium, antimony and tellurium species in water, urine, fish and soil extracts using HPLC/ICP-MS. AB - The stability of arsenic, selenium, antimony and tellurium species in water and urine (NIST SRM 2670n) as well as in extracts of fish and soil certified reference materials (DORM-2 and NIST SRM 2710) has been investigated. Stability studies were carried out with As(III), As(V), arsenobetaine, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), phenylarsonic acid (PAA), Se(IV), Se(VI), selenomethionine, Sb(III), Sb(V) and Te(VI). Speciation analysis was performed by on-line coupling of anion exchange high-performance liquid chromatography (HPLC) with inductively coupled plasma mass spectrometry (ICP-MS). Best storage of aqueous mixtures of the examined species was achieved at 3 degrees C whereas at 20 degrees C species transformation especially of selenomethionine and Sb(V) took place and a new selenium species appeared within a period of 30 days. Losses and species transformations during extraction processes were investigated. Extraction of the spiked fish material with methanol/water led to partial conversion of Sb(III), Sb(V) and selenomethionine to two new antimony and one new selenium species. The other arsenic, selenium and tellurium species were almost quantitatively extracted. For soil spiked with MMA, PAA, Se(IV) and Sb(III), recoveries after extraction with water and sulfuric acid (0.01 mol/L) were below 20%. PMID- 11220584 TI - Direct solid sampling electrothermal atomic absorption spectrometry for the analysis of high-purity niobium pentaoxide. AB - A direct solid sampling electrothermal atomic absorption spectrometry (SoS-ETAAS) method for ultratrace analysis of powdered niobium pentaoxide for Al, Co, Cr, Cu, Fe, K, Mg, Mn, Na, Ni and Zn has been developed. The elements K, Mg, Na and Zn could be determined without any chemical modification. However, in the determination of the elements Al, Co, Cr, Cu, Fe, Mn and Ni, serious matrix caused non-spectral interferences and background occurred which made their determination impossible. This problem was remedied by conversion of the niobium pentaoxide matrix into the thermally stable niobium carbide by using methane atmosphere during the pyrolysis stage. The development resulted in establishing an extraordinary powerful method for the analysis of niobium pentaoxide in term of limits of detection, accuracy, simplicity and analysis time. Quantification was performed using calibration curves measured with aqueous standard solutions. The accuracy was checked by comparing the results with those obtained by ETAAS in analysis of slurries and digests of the sample. Due to almost complete freedom of blank and high applicable sample amounts (up to 15 mg), extremely low limits of detection (0.5-2 ng/g) were achieved. PMID- 11220585 TI - Determination of metal additives and bromine in recycled thermoplasts from electronic waste by TXRF analysis. AB - A new method for analysis of metal additives in recycled thermoplasts from electronic waste was developed, based on dissolving the samples in an organic solvent and subsequent analysis of the corresponding solutions or suspensions by total-reflection X-ray fluorescence spectroscopy (TXRF). The procedure proved to be considerably less time consuming than the conventional digestion of the polymer matrix. Additives containing Ti, Zn, Br, Cd, Sn, Sb, and Pb were analyzed in a hundred randomly selected samples from recycling, which provided an overview of the range of elemental concentrations in thermoplasts utilized for consumer electronics. The results were validated independently by instrumental neutron activation analysis (INAA), subsequent regression analysis confirmed the trueness of the chosen approach. PMID- 11220586 TI - Determination of palladium in gasoline by neutron activation analysis and automated column extraction. AB - Palladium in gasoline was determined by means of neutron activation analysis (NAA) and selective sorbent extraction. Unleaded gasoline consistent with DIN EN 228, RON 95 was irradiated at a thermal neutron flux of phith = 1.68 x 10(13)s( 1)cm(-2) and an epithermal neutron flux of 3.32 x 10(11)s(-1)cm(-2) for t(irr) = 12 h. The irradiated gasoline was digested with nitric acid and palladium was then separated as N,N-diethyl-N'-benzoylthiourea complex by an automated column pre-concentration procedure. The eluate of 50 microL was dried on a filter paper and the 88.03 keV photons resulting from the decay of 109Pd were detected in a low level HPGe spectrometer with an efficiency of 35.5%. Severe interferences with other matrix constituents, especially 82Br could be overcome and the detection limit for palladium was improved to 3.4 ng/L at a confidence level of 90%. Although the analytical procedure applied yielded the lowest detection limit for palladium obtained in gasoline up to now, no indications for the presence of palladium were found. PMID- 11220587 TI - Multifunctional organic nitrates as constituents in European and US urban photo smog. AB - Air samples of the atmospheric ground layer in the cities of Ulm in Germany, Las Vegas, Nevada, and Salt Lake City, Utah, in the US were analyzed for organic nitrates. The air samples were taken around noon in summer at sunny weather conditions. 43 (C6-C13) alkyl mononitrates, 24 (C3-C6) alkyl dinitrates, and 19 (C2-C6) hydroxy alkyl nitrates have been identified. The analytical protocol included high-volume-sampling, NP-HPLC group separation, high resolution capillary gas chromatography, and detection by the highly selective mass spectrometer detector (SIM mode, m/z = 46). The levels of the sum of 15 (C6-C10) alkyl mononitrates ranged from 2.9 to 11.0 parts per trillion (ppt(v)). The levels of the sum of 21 (C3-C6) alkyl dinitrates ranged from 2.3 to 10.5 ppt(v), and the levels of the sum of 7 (C2-C4) hydroxy alkyl nitrates ranged from 7.3 to 28 ppt(v), respectively, in the urban air samples. These results emphazise the contribution of the alkyl dinitrates and hydroxy alkyl nitrates besides the alkyl mononitrates to the budget of NO(Y) compounds. No major differences in levels and pattern of the organic nitrates are present in air of the German and the US cities. PMID- 11220588 TI - Copper-complexation index as a polarographic summation parameter for the determination of chelating agents in water. AB - Polarography of the copper(II)-complexes of chelating agents is shown to be a suitable basis for a summation parameter for the total concentration of these chemicals in water (expressed as the copper-complexation index). Using 12 chelating agents (ATMP, BAED, CDTA, DTPA, DTPMP, EDTA, EDTMP, EDTP, EGTA, HEDP, NTA, PBTC) all listed in DIN 38409-H26 and DIN 38413-P5 a satisfactory reproducibility of the method used was obtained. In addition several commercial tensides, detergents in washing and deliming products were investigated. PMID- 11220589 TI - Simultaneous multi-element analysis of trace elements in soil samples by means of high-resolution inductively coupled plasma sector field mass spectrometry (SF-ICP MS). AB - The potential of SF-ICP-MS for trace element analysis in complex environmental matrices such as soil solutions was investigated. Spectral interferences found in mass spectra of soil matrices are presented in detail. Furthermore, the influences of single components of the soil matrix on the signal intensity of selected elements were studied. Detection limits of different elements are presented with respect to the composition of the matrix. A fast and accurate method for quasi-simultaneous determination of Al, Si, P, V, Cr, Mn, Fe, Ni, Co, Cu, Zn, As, Se, Sr, Mo, Cd, Sn, Hg and Pb in aqueous soil extracts was established. PMID- 11220590 TI - Metal(loid)organic compounds in contaminated soil. AB - 13 samples of soils contaminated with petrol, coaly residues, shredder and domestic waste have been investigated by low temperature gas chromatography with plasma mass spectrometry detection after sample derivatisation by hydride generation (HG/LT-GC/ICP-MS). 24 organic compounds of 9 elements could be analysed, one fifth of them exceeding the concentration of 1 microg/kg. These results are roughly comparable with those on harbour and river sediments, and are discussed in respect to a preliminary evaluation of the emission potential of solid waste and contaminated soil as well as waste treatment processes. PMID- 11220591 TI - Retention behavior of humic substances in reversed phase HPLC. AB - Recovery as well as appearance and abundance (in percent) of different fractions of humic substances are found to depend on injected sample amounts in reversed phase HPLC. Sample amounts have been varied both by varying sample concentration and sample volume. In case of lowest amounts injected only two fractions were obtained for a commercial humic acid sodium salt, i.e. one for excluded molecules and one for hydrophobic components. The abundance of excluded molecules decreases upon increasing amounts injected. Another three fractions are obtained upon increasing amount injected: a hydrophilic fraction and two hydrophobic ones. This behavior is explained by auxiliary equilibria between excluded components and humic molecules previously adsorbed on the stationary phase. PMID- 11220592 TI - Structural and elemental investigations of isolated aquatic humic substances using X-ray photoelectron spectroscopy. AB - Structural and elemental investigations of aquatic humic substances (HS) by means of X-ray photoelectron spectroscopy (XPS) are described. For that purpose small amounts (10-50 microg) of dissolved reference HS, which were characterized within the German research program DFG-ROSIG, were dried as thin films on small pieces of a high-purity silicon wafer. The photoelectrons from such HS layers exhibited characteristic signals of carbon C1s, nitrogen N1s, oxygen O1s and sulfur S2s, which could be fitted by Gaussian curves and used for the quantification of various moieties of HS: carbon (C-C, C-O, C=O, O=C-O), oxygen (C-O, C=O), nitrogen (C-N, C-N+) and sulfur. Moreover, by adding up the element signals of the HS samples their elemental composition of C, O, N and S was assessed. A comparison of the data based on solution state NMR and conventional elementary analysis revealed a satisfactory accuracy with those obtained by XPS. PMID- 11220593 TI - Characterization of high molecular weight cadmium species in contaminated vegetable food. AB - Spinach and radish grown from seeds were each contaminated with 4 different amounts of cadmium. After a cell breakdown of the eatable parts and centrifugation of the resulting homogenates all supernatants (cytosols) were separated by gel permeation chromatography (GPC). The size-range of the GPC method used was about 20-8000 kDa for globular proteins. The high molecular weight (HMW-Cd-SP, 150-700 kDa) and the low molecular weight Cd species (LMW-Cd SP, < 150 kDa) in all plant cytosols eluted at about the same retention volume by GPC. The most important Cd binding form in the cytosols of all plants was found to be HMW-Cd-SP. The Cd elution maxima were detected in the range of about 200 kDa. The Cd determinations were performed with ET-AAS by means of matrix modifier. By incubating chosen cytosols with a proteinase before the GPC it was verified that the HMW-Cd-SP in both vegetables are Cd proteins. The molar proportions protein/Cd were about 2-6 in the respective GPC fractions of the HMW Cd-SP of the highest contaminated plants. The GPC fractions of the HMW-Cd-SP of spinach and radish were further separated by a preparative, native and continuous polyacrylamide gel electrophoresis (PAGE) method. At pH 8 the species were negatively charged, had only a small UV-absorption at 280 nm and showed a very similar elution behavior in all analyzed cytosols. Therefore, we suppose that the HMW-Cd-SP of these two different vegetable foodstuffs have a very similar chemical structure. PMID- 11220594 TI - Electrothermal atomic absorption spectrometric determination of cobalt in biological samples and natural waters using a flow injection system with on-line preconcentration by ion-pair adsorption in a knotted reactor. AB - An on-line flow injection preconcentration-ETAAS method is developed for trace determination of cobalt in biological materials and natural samples by ion-pair sorption on the inner walls of a PTFE knotted reactor. The ion-pair is formed between the negatively charged cobalt-nitroso-R-salt complex and the tetrabutylammonium counter-ion. An enhancement factor of 15, a sampling frequency of 17 and a concentration efficiency of 4 are obtained for a preconcentration time of 60 s and a sample loading flow rate of 5 mL min(-1). The detection limit (3sigma) is 5 ng L(-1). The relative standard deviation at the 0.2 microg L(-1) level is 2.3%. The analytical results obtained for standard reference materials are in good agreement with the certified or indicated values and satisfactory recoveries of spiked cobalt in tap water are obtained. PMID- 11220595 TI - Study of the binding of 114mIn radiotracer to human serum components by ultrafiltration and chromatography. AB - The chemical speciation of indium in serum was studied. Ultrafiltration was used to investigate the influence of several buffer systems on the binding characteristics of indium in serum and to study the association of indium with transferrin and albumin. This was performed by means of batch incubation experiments with a 114mIn tracer. Different buffer systems were investigated. A series of bicarbonate, Tris:HCl and HEPES buffers were found to fit for this purpose. Phosphate buffer was not suitable, as it is capable of disrupting the binding between indium and transferrin. Batch ultrafiltration experiments with 114mIn incubated solutions of transferrin and albumin showed that both proteins are capable of binding indium to a high degree. Three chromatographic techniques (SEC, AEC, AC) were used to study the different chemically active species of indium in serum. It is concluded that next to transferrin, albumin is also responsible for the binding and transport of indium in serum. PMID- 11220597 TI - Stable isotope dilution analyses of molybdenum in meteorites. AB - Isotope dilution mass spectrometry is an ideal analytical technique to measure the elemental abundance of Mo in C1 carbonaceous chondrites and the metallic and troilite phases of iron meteorites. The mean abundance of Mo in two C1 meteorites is 0.909+/-0.040 microg/g which corresponds to a value of 2.55 atoms Mo with respect to Si equal to 10(6) atoms, which is identical to the currently accepted solar system abundance. The partitioning of Mo between the metallic and sulfide phases in the Mundrabilla iron meteorite was found to be 6.0+/-0.2 microg/g and 8.6+/-0.3 microg/g, respectively. A new, precise Mo concentration of 1.54+/-0.04 microg/g for the Geochemical Reference Standard BCR-1 is also reported. PMID- 11220598 TI - Analytical information needs in the XXI century. PMID- 11220596 TI - Low-molecular-weight organoiodine and organobromine compounds released by polar macroalgae--the influence of abiotic factors. AB - The influence of temperature, light, salinity and nutrient availability on the release of volatile halogenated hydrocarbons was investigated in the Antarctic red macroalgal species Gymnogongrus antarcticus Skottsberg. Compared to standard culture condition, an increase in the release rates of iodocompounds was generally found for the exposure of the alga to altered environmental conditions. Macroalgae exhibited higher release rates after adaptation for two months to the changed factors, than after short-term exposure. Monitoring the release rates during a 24 h incubation period (8.25 h light, 15.75 h darkness) showed that changes between light and dark periods had no influence on the release of volatile halocarbons. Compounds like bromoform and 1-iodobutane exhibited constant release rates during the 24 h period. The formation mechanisms and biological role of volatile organohalogens are discussed. Although marine macroalgae are not considered to be the major source of biogenically-produced volatile organohalogens, they contribute significantly to the bromine and iodine cycles in the environment. Under possible environmental changes like global warming and uncontrolled entrophication of the oceans their significance may be increase. PMID- 11220599 TI - A systematic approach to optimum working conditions with inductively coupled plasma atomic emission spectrometry. AB - Optimum experimental factors were determined for the analytical determination of Al, Cd, Fe, Pb, and Zn by ICP atomic emission spectrometry. Based on systematically determined factor levels, working conditions were found that gave similar, and sometimes better results compared with the hitherto used levels of factors. All measurements were performed with a sampling time of 150 ms as often used in routine analysis in the laboratory. This optimization resulted in a reduced outer plasma gas flow from 15 L/min argon to 12 L/min without any relevant changes of the achievable detection limits. A serious problem was that only one analytical line of Al could be used. A comparison with the lower limit of application (comparable with the detection limit) from German directive DIN 38406, part 22 ([1]), showed that the detection limits of Al and Fe are superior, whereas for Cd there was only little improvement. The detection limits of Zn and especially Pb are always higher than the lower range of application under these conditions. Therefore, the use of two device-parameter sets for hard and soft lines, respectively, is strongly suggested. Maps with the observed signal-to noise-ratios were systematically acquired for each element analyzed in connection with different strategies for optimum search. mon compromise condition (combined analysis) and the limits of quantification demanded in the German directive DIN 38406, part 22 [1]. Only four, but the most important, experimental factors were changed, the other experimental factors were always kept constant (Tables 1 and 2). PMID- 11220600 TI - Indirect fluorescence detection of phenolic compounds by capillary electrophoresis on a glass device. AB - A micromachined capillary electrophoresis system has been fabricated on a glass device for the separation and indirect fluorescence detection of phenols. Using this device two phenols viz., 2,4-dichlorophenol and pentachlorophenol, were separated within 12 s compared to under 19 min on a conventional capillary electrophoresis system using direct ultraviolet detection. The precision of the glass device ranged from 12.7%-16.7% compared to 0.42%-4.9% for the conventional system. Both systems showed good linearity in the concentration range of 0.8-6.38 mM for the glass device and 5-130 microM for the conventional system. The relationship between temperature and high voltage with baseline drift was also investigated. These results provide a foundation for the development of a miniaturised chemical analysis system for the on-line analysis of phenols in water. PMID- 11220602 TI - Applications of a versatile sol-gel derived renewable electrode for capillary electrophoresis. AB - A new electrode has been developed and applied for amperometric detection in capillary electrophoresis (CE), comprised of carbon sol-gel composite material. The versatility of the sol-gel technique permits the flexible configuration of the electrode. The performance of such a sol-gel carbon composite electrode (CCE) is first evaluated in a typical CE application for the detection of purine-based compounds. Application of the CCE is also demonstrated for the detection of phenolic compounds in a micellar system. Separation resolution for non-ionic phenolic compounds can significantly be enhanced by introducing sodium dodecyl sulfate (SDS) at a concentration above its critical micelle concentration (cmc) to the buffer. Another design of the CCE incorporating the electrocatalyst Cu2O is employed for the analysis of sugars and organic acids based on dynamic modification with cetyltrimethylammonium bromide (CTAB). It has been found that the presence of surfactant in the separation buffer does not adversely influence the electrochemical detection using a sol-gel derived carbon electrode. PMID- 11220601 TI - Needle-type glucose microbiosensor based on glucose oxidase immobilised in an overoxidised polypyrrole film (an in-vitro study). AB - A fast response, needle-type glucose microbiosensor has been fabricated by a one step electrochemical immobilisation of glucose oxidase in a polypyrrole film. The sensor shows a remarkable rejection of electroactive interferences, especially paracetamol. The maximum bias observed in the worst situation never exceeded the value of 6%. The fabrication procedure delivered very reproducible devices and the sensitivity of a newly prepared biosensor was typically 650 nA mM(-1) cm(-2). The kinetic parameters, obtained from an existing model, permitted to understand the sensor behaviour. PMID- 11220603 TI - Soil-modified carbon paste electrode: a useful tool in environmental assessment of heavy metal ion binding interactions. AB - Carbon paste electrodes (CPEs) modified with different soils in their native form were prepared to create a soil-like solid phase suitable for application in studies of heavy metal ion uptake and binding interactions. The preparation of CPEs modified with five different soils was examined and their heavy metal ion uptake behavior investigated using a model Cu(II) aqueous solution. Metal ions were accumulated under open circuit conditions and were determined after a medium exchange using differential pulse anodic stripping voltammetry, applying preelectrolysis at -0.7 V. The soil-modified CPE accumulation behavior, including the linearity of the current response versus Cu(II) concentration, the influence of the pH on the solution, and the uptake kinetics, was thoroughly investigated. The correlation between the soil-modified CPE uptake capability and the standard soil parameters, such as ion exchange capacity, soil pH, organic matter and clay content, were evaluated for all five examined soils. The influence of selected endogenous cations (K(I), Ca(II), Fe(III)) on the transfer of Cu(II) ions from a solution to the simulated soil solid phase was examined and is discussed. Preliminary examinations of the soil-modified CPE uptake behavior with some exogenous heavy metal ions of strong environmental interest (Pb(II), Hg(II), Cd(II) and Ag(I)) are also presented. This work demonstrates some attractive possibilities for the application of a soil-modified CPE in studying soil-heavy metal ion binding interactions, with a further potential use as a new environmental sensor appropriate for fist on-site testing of polluted soils. PMID- 11220604 TI - Determination of underivatized amino acids by high-performance liquid chromatography and electrochemical detection at an amino acid oxidase immobilized CuPtCI6 modified electrode. AB - An amperometric sensor for amino acids based on the immobilization of amino acid oxidase on the surface of a CuPtCl(6)/GC is described. The amperometric current is due to the oxidation of H2O2 liberated during the enzyme reaction on the surface of the enzyme electrode. The electrode response characteristics as well as kinetic parameters have been evaluated. The enzyme electrode was characterized as an electrochemical biosensor, which was used as detector in high performance liquid chromatography (HPLC) for the determination of a mixture of amino acids with satisfactory results. PMID- 11220605 TI - Effects of various salts on the determination of arsenic by graphite furnace atomic absorption spectrometry. Direct determination in seawater. AB - The effect of Na, Mg, Ca and Sr as their nitrate, chloride and sulfate salts and seasalt, with and without the use of palladium, on the determination of arsenic by electrothermal atomic absorption spectrometry was investigated. In the absence of any stabilizing agent, arsenic was partially lost as molecular species at low temperatures. The effect of salts on the shape of the atomization signal, the integrated absorbance and the stabilizing effect were highly dependent both on their nature and mass. By trapping arsenic, oxide species resulting from the decomposition of nitrate salts induced a high stabilization effect depending on their vaporization temperatures: MgO approximately CaO>SrO>Na2O. The stabilization effect of chlorides occurred about 200 degrees C lower and depended on mass, volatility and hydrolytic properties: SrCl2>CaCl2>MgCl2 approximately NaCl. The effect of sulfates was mainly dependent on their decomposition/vaporization mechanisms, and in the presence of Na2SO4 or CaSO4 a strong chemical interference effect was observed. Palladium stabilized arsenic in the presence of nitrates, chlorides or even sulfates, leading to a similar delaying effect, signal shape and integrated absorbance. Seasalt induced also important modifications to the atomization signal of As. Moreover, an interference effect was observed, which could probably be attributed to the simultaneous vaporization of sulfate in seasalt. In seawater, Pd suppressed this interference effect and permitted to use a high pyrolysis temperature up to 1400 C to remove the major part of the seawater matrix before atomization. Under optimized conditions, the detection limit for As obtained in unmodified seawater in the presence of Pd was 0.34 microg L(-1) for a 10 microl sample. PMID- 11220606 TI - Determination of cobalt in sewage sludge using ultrasonic slurry sampling graphite furnace atomic absorption spectrometry. AB - Cobalt in sludge of domestic and industrial origin, with high iron contents (> 17 g/kg), was determined by slurry sampling graphite furnace atomic absorption spectrometry (GF-AAS). Slurries prepared by ultrasonic stirring were adequately diluted to cover the variation in cobalt content in the sludge samples. The diluent was 5% HNO3. Standard atomisation conditions for cobalt determination were used and no matrix modifier was applied. Slurry sampling GF-AAS results in the sludge were verified by analysing totally digested samples by inductively coupled plasma atomic emission spectrometry (ICP-AES) and by GF-AAS. The procedure was validated by analysing the certified reference material BCR 146 R, a sewage sludge of industrial origin. Recoveries for cobalt in the spiked slurried sludge samples ranged from 92 to 96%, with a relative standard deviation of 10%. Recoveries in the certified sludge using slurry sampling GF-AAS technique were about 103% for a cobalt content of 7.39 mg/kg. PMID- 11220607 TI - Rapid determination of lead and cadmium in sewage sludge samples using electrothermal atomic absorption spectrometry with slurry sample introduction. AB - Lead and cadmium concentrations in sewage sludge samples are determined by suspending the ground samples in a solution containing 10% (v/v) concentrated hydrofluoric acid, 1% (v/v) concentrated nitric acid, 0.5% (m/v) dihydrogen ammonium phosphate and 0.1% (m/v) sodium hexametaphosphate. Aliquots of 20 microL of these suspensions (4 mg/mL) are diluted to 1000 microL with the same solution and then injected into the electrothermal atomizer. The drying stage is performed by programming a 400 degrees C temperature, a ramp time of 20 s and a hold time of 15 s on the power supply of the atomizer. No ashing step is used. Platform atomization is carried out at 1600 and 1800 degrees C for Pb and Cd, respectively. Calibration is performed using aqueous standards in the 5-75 and 0.2-5 microg/L Pb and Cd ranges, respectively. Results obtained for three certified reference materials and four samples demonstrate the reliability of the procedures described. PMID- 11220608 TI - Optimization and comparison of MAE, ASE and Soxhlet extraction for the determination of HCH isomers in soil samples. AB - The microwave-assisted extraction (MAE), accelerated solvent extraction (ASE) and Soxhlet extraction of two isomers of hexachlorocyclohexane, alpha-HCH and gamma HCH, from a polluted landfill soil have been optimized following different experimental designs. In the case of microwave-assisted extraction, the following variables were considered: pressure, extraction time, microwave power, percentage of acetone in n-hexane mixture and solvent volume. When ASE extraction was studied the variables were pressure, temperature and extraction time. Finally, the percentage of acetone in n-hexane mixture and the extraction time were the only variables studied for Soxhlet extraction. The concentrations obtained by the three extraction techniques were, within their experimental uncertainties, in good agreement. This fact assures the possibility of using both ASE and MAE techniques in the routine determination of lindane in polluted soils and sediments. PMID- 11220609 TI - Graphite furnace-atomic absorption spectrophotometric determination of palladium in soil. AB - A new and sensitive procedure for the graphite furnace-atomic absorption spectrophotometric (GF-AAS) determination of Pd in soil at nanogram level is described. The method is based on prior separation and enrichment of the metal as Pd(II)-SnCl3- -N-butylacetamide (BAA) complex into 1-pentanol (PN) by solvent extraction method. The value of the molar absorptivity of the complex in three solvents, i.e. ethyl acetate, 1-pentanol, chloroform, lie in the range of (0.70 2.75) x 10(4) L mol(-1) cm(-1) at lambda(max) 360-440 nm. The metal could be enriched into organic solvent, i.e. PN, up to 10-folds. The sensitivity (A = 0.0044) of the method in the term of the peak height was 0.5 ng Pd/mL of the aqueous solution at an enrichment factor (EF) of 5. Optimization of analytical variables during enrichment and GF-AAS determination of the metal are discussed. The method has been applied for the analysis of Pd to soil samples derived from roads and highways in Germany. PMID- 11220610 TI - A DANREF certified reference plastic for measurement of overall migration into the food simulant olive oil by single sided testing. AB - A reference material for the determination of overall migration from a plastic coextrudate into the fatty food simulant olive oil was produced and certified in an interlaboratory study. The analyses were carried out according to the ENV 1186 standard from the European Committee for Standardization (CEN) [ 1, 2, 3] with exposure of the coextrudate to olive oil for 10 days at 40 degrees C. After an initial preliminary interlaboratory study eight laboratories participated in the certification round, and two different methods were used to obtain single sided exposure of the plastic to the oil. The certified value was determined as the mean of laboratory mean values. No outliers were found. A reference value of 8.6 mg/dm2 +/- 1.4 mg/dm2 (+/- half width of the 95% confidence interval) was obtained which is within the range relevant for the regulatory limit (10 mg/ dm2), making this reference material suitable for laboratories measuring according to the EU overall migration limit [4]. The material has been found stable over 45 months. PMID- 11220611 TI - Determination of some trace elements in human tooth enamel. AB - Determination of seven elements (Cu, Fe, Mg, Mn, Pb, Sr and Zn) in whole enamel and surface layers of extracted non-carious human teeth by FAAS, ETA AAS, ICP-AES and ICP-MS (Pb) is demonstrated. Techniques are described for obtaining whole enamel and its acid dissolution. Fifty microm width enamel layers from outer enamel surface to a 200 microm depth were successively etched in 1 mL of 3 M HClO4 for 3 min dissolution periods. Enamel samples were analyzed for populations under and over 20 years of age and enamel from Bronze Age teeth. Concentrations of microelements in the whole enamel and in the first surface layer (50 microm depth) were compared. With exception of Sr and Mg, all elements show significantly higher concentrations in the first layer than in whole enamel and higher concentration in teeth of individuals over 20 years, which demonstrate the cumulative effect of these elements. The Cu, Fe, Mn, Pb and Zn concentrations in four layers of erupted and non-erupted teeth decreased while Mg and Sr concentrations increased toward enamel-dentine junction. The concentrations of most elements were almost constant as they approached the 150 microm layer. This concentration gradient may result from interaction between saliva and teeth and supports the hypothesis that the surface de- and re-mineralization process is effective at most to 150 microm from the enamel surface. PMID- 11220612 TI - The determination of certain major and minor elements in geological samples by inductively coupled plasma atomic emission spectrometry. Some interference problems with the analysis of geological standard reference materials and nutrition supplements. AB - Direct ICP-AES measurements of the digested geological standard reference material samples yielded the wrong information about their composition. The differences between certified and measured concentrations of the samples were due to the complicated sample matrix. The measured concentrations can be successfully corrected by using a multiple linear regression technique. The correction is based on the multiple regression line calculated from the analytical results at synthetic mixtures of matrix elements, where concentrations varied on five levels. There were no significant (P = 0.05) differences between certified and measured concentrations in standard reference materials after the correction. The same method was used in the analysis of nutrition supplements. PMID- 11220613 TI - How faster and cheaper to determine chromium by adsorptive cathodic stripping voltammetry in the presence of DTPA and nitrate. AB - A modification of the voltammetric procedure for the determination of chromium in the presence of DTPA and nitrates was proposed. Morpholinoethanesulfonic (MES) acid and its sodium salt were used for stabilisation of pH instead of acetate buffer. In the presence of MES the determination of chromium can be carried out in the presence of dissolved oxygen without decrease of sensitivity of the measurements. Elimination of the purge step decreases total analysis time and saves gas. PMID- 11220614 TI - Analytical control of silica glass production. Voltammetric determination of titanium and iron in raw materials and silica glass samples. AB - Adsorptive stripping voltammetric (AdSV) methods are presented for the determination of titanium and iron in quartz and silica glass samples obtained after pressure decomposition. Mandelic acid and catechol were used as complexing agents for titanium and iron, respectively. The method for titanium determination is based on the catalytic effect of chlorate ions. An insoluble residue remaining after decomposition of quartz and silica glass samples in HF+H2SO4 mixture was checked by energy-dispersive X-ray analyses. ET-AAS was applied as a reference method to AdSV measurements. PMID- 11220615 TI - A cell biology approach to microbial pathogenesis. PMID- 11220616 TI - EMBO-EBNIC workshop on cellular microbiology 'Host cell-pathogen interactions in infectious disease'. PMID- 11220617 TI - Immunogenetic aspects of the cellular immune response of Drosophilia against parasitoids. AB - Host-parasite relationships represent integrating adaptations of considerable complexity involving the host's immune capacity to both recognize and destroy the parasite, and the latter's ability to successfully invade the host and to circumvent its immune response. Compatibility in Drosophila-parasitic wasp (parasitoid) associations has been shown to have a genetic basis, and to be both species and strain specific. Studies using resistant and susceptible strains of Drosophila melanogaster infected with virulent and avirulent strains of the wasp Leptopilina boulardi demonstrate that the success of the host cellular immune response depends on the genetic status of both host and parasitoid. Immunological, physiological, biochemical, and genetic data form the bases of a two-component model proposed here to account for the observed specificity and complexity of two coevolved adaptations, host nonself recognition and parasitoid virulence. PMID- 11220618 TI - Population coverage by HLA class-I restricted cytotoxic T-lymphocyte epitopes. AB - Vaccination using cytotoxic T-lymphocyte (CTL) epitopes has become a widely used immunization strategy, especially because their structure makes them an attractive alternative to the delivery of whole proteins as immunogens. Nonetheless, their use is limited, in particular because of their specificity, being recognized only by cognate HLA alleles. The potential for immunizing a substantial portion of an ethnically diverse population using a modest number of peptides has been aided by the identification of HLA supertypes. However, the derivation of epitopes is often guided by methods that do not guarantee cross reactivity, so we consider the feasibility of providing vaccine coverage to a multi-ethnic population under different assumptions. In particular, two large datasets are used to estimate the number of peptides needed to provide > or =90% group-specific coverage of a multiethnic population, when specificity is assumed to be either to a single serologic or molecular type. These assumptions are evaluated utilizing a clinically important epitope repertoire derived from two human cytomegalovirus proteins, and data on the in vitro memory response elicited by these peptides is presented. In summary, our combined theoretical and empiric studies suggest that 90% coverage of some ethnic groups is attainable with 11 uniquely defined HLA-restricted CTL epitopes. The derivation of four or more additional CTL epitopes is needed to attain 90% coverage of Blacks or Asians, the minimally covered groups. Ninety percent coverage of all major ethnic groups in a multi-ethnic population appears feasible without relying on cross-reactivity, but may require two to three times more CTL epitopes than estimated for serologic data, homogenous populations, or HLA alleles grouped as supertypes. PMID- 11220619 TI - Characterization of the MHC class I region of the Japanese pufferfish (Fugu rubripes). AB - A BAC map of the Japanese pufferfish (Fugu) MHC class I region was constructed using a mixture of sequence scanning and sequence-tagged site mapping methodologies. The Fugu MHC class Ia genes are linked to genes which are found within the human classical MHC class II and extended class II regions, a situation which has been found in the MHC of all teleosts mapped so far. The 300 kb contig comprises 24 MHC-related genes and is bounded by six non-MHC genes, which are thought to represent an evolutionary breakpoint within the region. Comparative analysis with both human and zebrafish MHC maps indicates two blocks of genes (KNSL2, ZNF297, DAXX, TAPBP, FLOTILLIN; and PSMB8, PSMB10, PSMB9, ABCB3, FABGL, BRD2, COL11A2, RXRB) which have remained linked over 400 million years and may represent an ancestral arrangement of the vertebrate MHC. Zebrafish and Fugu diverged between 100-200 million years ago and differences exist between these two fish species. The position and number of MHC class Ia genes is not conserved between species, there is an inversion of a block of nine genes centering on the PSMB cluster, and additional genes are present in zebrafish coding for a transport-associated protein and a beta proteasome subunit. The extent of these differences has implications for the extrapolation of fish model organism data to commercial aquaculture species. The data presented here represent the most extensive analysis of a fish MHC class Ia region described so far and clearly delimit the extent of this region in Fugu and, potentially, all teleosts. PMID- 11220620 TI - Haplotype-specific sequence encoding the protein kinase, interferon-inducible double-stranded RNA-dependent activator in the human leukocyte antigen class II region. AB - The protein kinase, interferon-inducible double-stranded (ds)RNA-dependent activator (PRKRA) is a dsRNA-binding protein which activates a protein kinase participating in the antiviral activity of interferon. Our previous studies indicated that the nucleotide sequence encoding PRKRA, which appeared to be an intronless gene, was present in PAC HS265J14 containing the human leukocyte antigen (HLA) DR subregion. In this study, we further investigated and characterized the PRKRA gene on the human genome by means of Southern blotting and polymerase chain reaction with homozygous typing cell lines for HLA genes. Results indicated that the presence of PRKRA in the DR subregion was dependent on the DR53 group. Consistently, fluorescence in situ hybridization profiles with PRKRA as a probe showed that the hybridization signal on Chromosome (Chr) 6p21.3 was seen only in the samples carrying the DR haplotypes that belonged to the DR53 group. Interestingly, another hybridization signal, which was mapped on Chr 2q31.2-q32.1, was always detected in the samples examined, i.e., even in the samples negative for the DR53 group. The outcome of a sequence-database homology search further indicated that the PRKRA gene with introns appeared to be present in a recently opened draft-sequence, RP11-65L3 (GenBank accession number AC009948), which is located between D2S335 and D2S2257. Together, the data presented here indicate that the PRKRA gene in the DR subregion is a processed pseudogene (PRKRApsi), which could have been generated only on the DR53 common ancestor's genome, and that the master copy of PRKRApsi is most probably present on Chr 2q31.2-q32.1. PMID- 11220621 TI - Distribution of natural killer cell immunoglobulin-like receptor sequences in three ethnic groups. AB - Killer cell immunoglobulin-like receptors (KIRs) are members of a group of molecules that specifically recognize HLA class I ligands and are found on subsets of human lymphopoetic cells. The number of KIR loci can vary between individuals, resulting in a heterogeneous array of possible KIR genes. The range of observed profiles has been explained by the occurrence of two haplotype families termed A and B which can be distinguished on the basis of certain KIR sequences. Here we attempted to determine whether the frequencies of putative KIR loci and the two haplotype groups vary in three ethnically defined, healthy, and unrelated control populations, namely UK Caucasoid (n=136), Palestinian (n=105) and Thai (n=119). We molecularly typed genomic DNA for the presence of 12 putative KIR loci, KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR3DL1, KIR3DL2, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS4, KIR2DS5, and KIR3DS1, using modified PCR sequence specific primers. The patterns of KIR locus frequencies combined with the similar linkage disequilibrium values suggest that there was a distinction in the distribution of the two broad haplotype groups between the populations studied. The A haplotype was always the most prevalent, but the ratio of A to B varied between populations. The frequency of B haplotype was highest in the Palestinians and lowest in the Thais (Pc<0.0001). PMID- 11220622 TI - Genomic structure, alternative splicing, and physical mapping of the killer cell lectin-like receptor G1 gene (KLRG1), the mouse homologue of MAFA. AB - The mouse killer cell lectin-like receptor G1 (KLRG1), the mouse homologue of the mast cell function-associated antigen (MAFA), is an inhibitory C-type lectin expressed on natural killer (NK) cells and activated CD8 T cells. Here we report the complete nucleotide sequence, alternatively spliced variants, and the physical mapping of the KLRG1 gene in the mouse. The gene spans about 13 kb and consists of five exons. Short interspersed repeats of the B1 and B2 family, a LINE-1-like element, and a (CTT)170 triplet repeat were found in intron sequences. In contrast to human KLRG1 and to the murine KLR family members, mouse KLRG1 locates outside the NK complex on Chromosome 6 between the genes encoding CD9 and CD4. PMID- 11220623 TI - Functional analysis of 5' and 3' regions of the closely related Ly49c and j genes. AB - The Ly49 multigene family consists of at least 14 closely related genes located in the natural killer (NK) gene complex on mouse Chromosome 6. Reverse transcriptase (RT)-PCR on single NK cells has shown that Ly49c is expressed on approximately 50% of NK cells, whereas the closely related Ly49j gene is expressed on 5-8% of NK cells. In this study, we examined three regions to determine whether they contain cis-acting elements involved in regulating the expression of these two closely related Ly49 genes within NK cells. Luciferase reporter assays in EL-4 cells suggested that the 5' regions of Ly49c and j contain promoter elements and repressor sequences. In addition, luciferase assays suggest that Ly49j also contains an active promoter in the first intron, although the transcripts produced from this promoter appear to be severely truncated. Finally, comparisons of the 3' noncoding regions of Ly49c and j revealed that the sequence of Ly49j diverges completely from Ly49c 130 bp downstream of the termination codon. The polyadenylation signal for Ly49j is located downstream of the Ly49c poly(A) site, which results in a much longer 3' untranslated region (UTR). When the Ly49j 3'UTR was used to provide the polyadenylation signal for the green fluorescent protein (GFP) reporter gene, GFP expression was reduced twofold. These results suggest that both internal promoters, repressors, and 3' regions play a role in regulating Ly49 gene expression. PMID- 11220624 TI - Preferential ADV-AJ association during recombination in the mouse T-cell receptor alpha/delta locus. AB - The gene coding for a T-cell receptor (TCR) alpha chain is assembled from variable (ADV) and joining (AJ) genes located on Chromosome 14. Each of the 90 ADV genes can rearrange with any one of the 61 AJ genes. We have previously demonstrated that ADV and AJ gene segment use evolves with time, with a progressive opening of ADV and AJ regions of the locus. To define the rules governing the use of AJ genes by ADV genes belonging to one family, we carried out a detailed analysis of 268 combinations of ADV2 BALB/c transcripts. We found that the different ADV2 members use different sets of AJ genes depending on their location within the ADV locus: ADV2S7 (the most AJ proximal ADV2 member) rearranges mainly with the AJ genes located close to the TEA element, whereas 50% of the sequences for ADV2S8, which is distal to the AJ locus, use the most distal AJ genes. ADV2S5, an ADV2 member located in the middle of the ADV locus, is associated with a wider set of AJ genes, located in the center of the AJ locus. Taken together, our results indicate that, in addition to the progressive opening of the ADV and AJ loci, the chromosomal location of ADV and AJ genes is a factor affecting AJ use in BALB/c mice. PMID- 11220625 TI - DNA methylation contributes to tissue- and allele-specific expression of the T cell differentiation marker RT6. AB - We investigated the role of DNA methylation in gene regulation of the rat T-cell differentiation marker RT6. Analysis of the methylation status of various tissues revealed that the RT6 promoter was hypomethylated in RT6-expressing tissues, and methylated in nonexpressing ones. Remarkably, among RT6-nonexpressing tissues, the extent of methylated regions varied greatly between lymphatic tissues, where regions larger than 23 kb were methylated, and nonlymphatic tissues, where methylation was restricted to a 3- to 4-kb region surrounding the promoter. We have previously shown that cis-regulatory elements determine differential expression of the two RT6 alleles in a subpopulation of T cells. We now show that the RT6 alleles in these cells differed in their methylation status. The promoter region of the silent allele was methylated, while that of the transcribed allele was not. Upon treatment of RT6-nonexpressing thymoma cells with the methyltransferase inhibitor 5-azacytidine, RT6 expression was induced. In RT6 heterozygous hybridoma cells, expressing only one RT6 allele, induction of the silent, methylated RT6 allele was observed. Sensitivity of the RT6 promoter to DNA methylation was demonstrated by promoter-specific in vitro methylation, which inhibited RT6 promoter activity, while that of the SV40 promoter was not influenced. Our findings indicate that DNA methylation plays an important role in the control of monoallelic and tissue-specific RT6 expression. PMID- 11220626 TI - The first constant-domain (CH1) exon of human IGHG2 is polymorphic and in strong linkage disequilibrium with the CH2 exon polymorphism encoding the G2m(n+) allotype in Caucasians. AB - Here we describe a hitherto unknown proline/threonine polymorphism at residue 72 of the human IgG2 CH1 domain (EU numbering 189) and show that it is linked to the known valine/methionine polymorphism at residue 52 of CH2 (EU numbering 282) defining the G2m(n+)/G2m(n-) allotypes. We sequenced the entire constant region of the heavy-chain gene for secreted IgG2 in five IGHG2*02 homozygous individuals covering CH1, hinge, CH2, and CH3 regions (approximately 2 kb). Proline 72 in CH1 of G2m(n-) is changed to threonine in the G2m(n+) [G2m(23)] allotype. Based on the crystal structure of human IgG1, this amino acid position is expected to be surface exposed in IgG2. Besides this structural difference, we identified two silent nucleotide polymorphisms in the CH1 region and seven in the introns. Finally, we developed a sequence-specific PCR typing system detecting the polymorphisms in the CH1 and CH2 regions. We typed 64 Danish Caucasians and found that the CH1 and CH2 region polymorphisms are in complete linkage disequilibrium in this population. PMID- 11220627 TI - Ethnic differences in allelic associations of the interleukin-1 gene cluster in South African patients with inflammatory bowel disease (IBD) and in control individuals. AB - The allelic frequencies of TaqI, PstI, and variable number of tandem repeat (VNTR) polymorphisms of the IL-1beta, IL-1 receptor (IL-1Re), and IL-1 receptor antagonist (IL-1Ra) respectively, were investigated in black and white patients with inflammatory bowel diseases (IBD) and compared with control individuals. Plasma concentrations of IL-1beta and IL-1Ra were also determined in these individuals. The IL-1beta TaqI(-) allele was significantly more frequent in 50 white IBD patients (60%) compared with 47 white controls (17%), and 20 black patients (20%) (P=0.00001 and P=0.0001, respectively). The IL-1Re PstI(-) allele was significantly more frequent in 20 black patients (75%) compared with 50 white patients (44%) (P=0.0001). The frequency of the IL-1Ra 240-bp allele was lower in black (12%) compared with white controls (25%), (P=0.0151), and the 410-bp allele was more frequent in black (87%) compared with white (73%) controls (P=0.0096). Linkage disequilibrium was found in black individuals homozygous for the 410-bp allele of IL-1Ra, and the PstI(-) allele of IL-1Re (84%) (P=0.0032). There was a significantly increased level of IL-1Ra in black patients compared with white patients and black controls (P=0.0006 and P=0.0008, respectively). The population differences in allelic frequencies of the IL-1 gene cluster and IL-1Ra concentrations suggest that genetic and environmental factors play an important role in susceptibility to IBD. PMID- 11220628 TI - Molecular cloning of the complement (C1r/C1s/MASP2-like serine proteases from the common carp (Cyprinus carpio). AB - The classical pathway of complement composed of C1, C4, and C2 is an antibody dependent activation cascade that is present in jawed vertebrates. C1 is a Ca2+ dependent complex of C1q, C1r, and C1s, and analogous to an initiation complex of the lectin pathway of complement, which consists of the mannose-binding lectin (MBL) homologous to C1q and the MBL-associated serine proteases (MASPs) homologous to C1r and C1s. Thus divergence of Clq and MBL and that of C1r, C1s and the MASPs are considered to be crucial events in the establishment and evolution of the classical complement pathway. However, molecular information on the C1 subcomponents is very limited in lower vertebrates. Here we describe two distinct C1r/C1s/MASP2-like cDNA clones (C1r/s-A, C1r/s-B) isolated from the common carp (Cyprinus carpio). They share 83% identity at the amino acid level and have a domain structure similar to that of C1r/C1s/MASPs from other species. The serine protease domain of the carp homologues lacks the histidine loop and is encoded by a single exon containing an AGY codon for the active serine residue, as in mammalian C1r, C1s, and MASP2. Southern blot and PCR analyses indicated that the carp has at least three copies of the C1r/s-A gene and a single C1r/s-B gene. Although phylogenetic tree analysis does not definitively assign carp C1r/s A and C1r/s-B, they might represent ancestral molecules which later diverged into C1r, C1s, and MASP2 of higher vertebrates. PMID- 11220629 TI - The recombination-activating gene 1 of Pleurodeles waltl (urodele amphibian) is transcribed in lymphoid tissues and in the central nervous system. AB - The recombination-activating gene 1 (RAG1) product is required for the somatic rearrangement of immunoglobulin and T-cell receptor genes. We cloned and sequenced the large continuous open reading frame coding for the salamander Pleurodeles waltl RAG1 protein. Semi-quantitative RT-PCR experiments were performed to quantify the expression of RAG1 in different tissues. The strongest signal was observed in the thymus of juvenile animals, confirming the primary lymphoid nature of that organ. Weaker expression was observed in the spleen, brain, and eyes of adults. Signals in these tissues represented 5.5%, 4.6%, and 2.0%, respectively, of the signal detected in the thymus. Expression in brain was confirmed by in situ hybridization. Similarly, low amounts of RAG1 transcripts were previously detected in the mouse brain. Moreover, the transcription of RAG1 begins as early as the neurula stages of development. These data suggest that the RAG1 protein could play a role in the central nervous system of vertebrates. PMID- 11220630 TI - The CD45 locus in cattle: allelic polymorphism and evidence for exceptional positive natural selection. AB - Cattle in Africa are a genetically diverse population that has resulted from successive introduction of Asian Bos indicus and European B. taurus cattle. However, analysis of mitochondrial genetic diversity in African cattle identified three lineages, one associated with Asian B. indicus, one with European B. taurus, and a third ascribed to an indigenous African sub-species of cattle. Due to their extended coevolution, indigenous African herbivores are generally tolerant to endemic African pathogens. We are interested in identifying alleles derived from the indigenous African cattle that may be associated with tolerance to African pathogens. An analysis of the locus which encodes the abundant plasma membrane-associated tyrosine phosphatase, CD45, identified three highly divergent allelic families in Kenya Boran cattle. Analysis of allelic distribution in a diverse range of cattle populations suggests a European B. taurus, an Asian B. indicus, and an African origin. This demonstrates not only significant allelic polymorphism at the CD45 locus in cattle but also convincing autosomal evidence for a distinct African sub-species of cattle. Furthermore, maximum-likelihood analysis of selection pressures revealed that the CD45 locus is subject to exceptionally strong natural selection which we suggest may be pathogen driven. PMID- 11220631 TI - Localization of the Rh50-like protein to the contractile vacuole in Dictyostelium. AB - The human Rhesus (Rh) family consists of three polytopic membrane proteins present at the cell surface of red blood cells. Although Rh proteins are essential for the expression of the blood group system their biological function remains unclear. In this study, the gene encoding a protein homologous to Rh50 in Dictyostelium discoideum was sequenced. The Rh50-like protein was localized to the contractile vacuole, the organelle responsible for maintenance of osmotic equilibrium within the cell. However, Rh50-like-deficient mutants in which the Rh50-like gene was disrupted did not appear to exhibit a phenotype related to osmoregulation. Nevertheless, these mutants may provide a valuable tool for studying the function of the rhesus protein. PMID- 11220632 TI - Haplotypic single nucleotide polymorphisms in the central MHC gene IKBL, a potential regulator of NF-kappaB function. PMID- 11220634 TI - Negative association of the HLA-DRB1*1502-DQB1*0601 haplotype with human narcolepsy. PMID- 11220633 TI - Mapping of the chicken and mouse genes for toll-like receptor 2 (TLR2) to an evolutionarily conserved chromosomal segment. PMID- 11220635 TI - Molecular cloning of CS1, a novel human natural killer cell receptor belonging to the CD2 subset of the immunoglobulin superfamily. PMID- 11220636 TI - Mechanism of the inhibitory effect of protease inhibitor on tumor necrosis factor alpha production of monocytes. AB - If the inflammatory response becomes excessive or uncontrolled by some stimuli, inappropriate inflammatory responses occur. Monocytes are extremely important cells for regulating the cytokine network and tumor necrosis factor alpha (TNFalpha) and interleukin- (IL) 10, which are mainly synthesized by monocytes, are representative cytokines that play a central role in the cytokine network. Protease inhibitors such as gabexate mesilate (GM) and ulinastatin (UTI) have been shown to have various beneficial effects by inhibiting the activation of leukocytes, but the mechanism for this has yet to be fully elucidated. In this study we investigated the mechanism of the inhibitory effect of protease inhibitors on the proinflammatory cytokine production of lipopolysaccharide- (LPS) stimulated monocytes. LPS-stimulated monocytes were treated with GM or UTI. The value of TNFalpha and IL-10 in the culture medium of monocytes was measured and each mRNA expression was assayed. The inhibitory effect of protease inhibitors on the activity of intracellular signal transduction pathways such as protein kinase C (PKC) and nuclear factor kappa B (NFkappaB) were also evaluated. GM decreased the TNFalpha production of LPS-stimulated monocytes as shown by the inhibition of mRNA expression and increased the IL-10 production of LPS stimulated monocytes. GM also suppressed the NFkappaB activity of LPS-stimulated monocytes. UTI decreased the TNFalpha production of LPS-stimulated monocytes, but did not inhibit the TNFalpha mRNA expression. The present study shows that the inhibitory effect of GM on the TNFalpha production of activated human monocytes is mediated by the suppression of NFkappaB activation, while the mechanism of UTI inhibiting TNFalpha production of human monocytes may be due to the inhibition of either the translation or secretion of TNFalpha. PMID- 11220638 TI - Protective effect of allopurinol on hepatic energy metabolism in ischemic and reperfused rat liver. AB - Reactive oxygen species generated by xanthine oxidase during reperfusion of ischemic liver might in part be responsible for ischemic organ injury. In normothermic ischemia/reperfusion rat model, we investigated whether allopurinol pretreatment improved ischemia-induced mitochondrial dysfunction. Rats were subjected to 60 min of hepatic ischemia and to 1 h and 5 h of reperfusion thereafter. At 18 h and 1 h before ischemia, the animals received 0.25 mL of either saline or allopurinol (50 mg/kg) i.p. In saline-treated ischemic rats, serum aspartate aminotransferase levels increased significantly at 5 h (4685 +/- 310 IU/L) and were significantly reduced with allopurinol pretreatment. Similarly, mitochondrial lipid peroxidation was elevated in the saline-treated ischemic group, but this elevation was prevented by allopurinol. In contrast, mitochondrial glutamate dehydrogenase activity and ketone body ratio decreased in the saline-treated group, but this decrease was also inhibited by allopurinol. Hepatic ATP levels in the saline-treated rats were 42% lower 5 h after reperfusion. However, treatment with allopurinol resulted in significantly higher ATP levels. Allopurinol treatment preserved the concentration of AMP in ischemic liver but inhibited the accumulation of xanthine in reperfused liver. Our findings suggest allopurinol protects against mitochondrial injury, which prevents a mitochondrial oxidant stress and lipid peroxidation and preserves the hepatic energy metabolism. PMID- 11220637 TI - Simultaneous measurement of hepatic tissue pH, venous oxygen saturation and hemoglobin by near infrared spectroscopy. AB - The purpose of this study was to investigate the feasibility of using near infrared (NIR) spectroscopy of the liver to simultaneously assess oxygen content in combination with tissue pH, an indicator of anaerobic metabolism. Six anesthetized swine were subjected to 45 min of hemorrhagic shock followed by resuscitation with blood and crystalloid. Calibration models between NIR spectra and reference measurements of tissue pH, hepatic venous oxygen saturation (S(V)O2), and blood hemoglobin concentration (Hb) were developed using partial least-squares regression. Model accuracy was assessed using cross validation. The average correlation (R2) between NIR and reference measurements was 0.87, 0.68, and 0.93, respectively for pH, Hb, and S(V)O2. Estimated accuracy, the root mean squared deviation between spectral, and reference measurements was 0.03 pH units, 0.3 g/dL, and 6%. NIR determination of hepatic oxygen content and tissue pH during shock and resuscitation demonstrated that there can be a variance between hepatic venous oxygenation and regional tissue acidosis. NIR spectroscopy provides a technique to explore the implications of post-shock depression of tissue pH and evaluate new methods of resuscitation. PMID- 11220639 TI - Immune potential of lymph node-derived lymphocytes in uncontrolled hemorrhagic shock. AB - The state of T cell immunity was evaluated in rats in early (1-4 h) hemorrhagic shock induced by a massive splenic injury. T cell subpopulations from treated and untreated shocked animals were tested by flow cytometry and the results were compared with healthy controls. A fall in CD4+ T lymphocyte and natural killer (NKR-P1+) cell number, marked decline in the T helper (CD4+) to T suppressor (CD8+) ratio, and decrease of interleukin-2 receptor (IL-2R) bearing cells in peripheral blood, mesenteric, and popliteal lymph nodes of rats was found in the early stages of hemorrhagic shock. The same phenotype profile was also revealed in lymphocytes of rats in hemorrhagic shock following massive splenic injury treated with Ringer's lactate. The number of TCRalpha beta and TCR-gamma delta positive cells, as well as the percentage of CD4 and CD8 positive cells in the thymus, was similar in all groups of rats. Culture of lymph node cells taken from rats following hemorrhage in the presence of 100 U/mL hrIL-2 resulted in a marked increase in the number of NKR-PI+ positive cells from 4.2% to 30.5% (P < 0.001). Magnet separated NKR-P1+ fractions lysed the allogeneic fibroblasts in the same manner as IL-2-activated NKR-P1 cells from the control rats. Popliteal lymph node (PLNi) CD8b+ lymphocytes from rats in hemorrhagic shock preinfected into the footpad with cytomegalovirus (CMV) 6 days prior to injury lost their ability to lyse the CMV-infected fibroblasts and protect the monolayer from CMV infection when compared with PLNi cells from control infected rats. The possible mechanisms for the observed cellular dysfunction following hemorrhage are discussed. PMID- 11220640 TI - Binding specificity of polymyxin B, BPI, LALF, and anti-deep core/lipid a monoclonal antibody to lipopolysaccharide partial structures. AB - The deep core/lipid A (DCLA) region of gram-negative bacterial lipopolysaccharide (LPS) is common to most gram-negative pathogens and contains anionic phosphoryl groups plus numerous acyl chains as part of the toxic lipid A moiety. Several disparate agents that antagonize the effects of LPS exhibit extensive physicochemical similarities (hydrophobicity, cationic charge) within their binding domains. It is presumed that binding to the DCLA region by each of these antagonists-cross-reactive anti-LPS monoclonal antibodies (mAbs), polymyxin B (PmB), plus bactericidal permeability-increasing protein (BPI) and Limulus anti LPS factor (LALF)-may be related to these properties. Therefore, we hypothesized that in addition to secondary and tertiary protein conformation, electrostatic interactions involving the negatively charged phosphoryl groups, hydrophobic interactions involving the acyl chains of lipid A, or both might be important factors that promote LPS antagonism. Binding of PmB, BPI, LALF, or anti-DCLA mAb 1B6 to Salmonella minnesota monophosphoryl lipid A (MPLA), diphosphoryl lipid A (DPLA), and Salmonella minnesota Re (which possess a common structural moiety, but vary considerably in structure and charge) was examined. Highly phosphorylated DNA and bovine serum albumin served as unrelated structural controls. BPI bound MPLA, which is hydrophobic and minimally charged, while mAb 1B6 bound anionic DNA; neither PmB nor LALF were reactive with MPLA or DNA. We surmised that hydrophobic interactions play a role in BPI binding to LPS, and although electrostatic interactions appear to be important for binding of mAb 1B6 to DCLA, they may not contribute to as great an extent for PmB, BPI, or LALF. Thus our data support the contention that the contribution of these specific physicochemical factors varies among endotoxin antagonists. PMID- 11220641 TI - The decrease of PKCalpha is associated with hepatic apoptosis at early and late phases of polymicrobial sepsis. AB - The present study investigates the relationship between the PKC-alpha and hepatic apoptosis during sepsis. Cecal ligation and puncture- (CLP) induced animal model of polymicrobial sepsis was used, with early and late sepsis referring to those animals sacrificed at 9 and 18 h, respectively, after CLP. The expressions of PKCalpha and Bcl-2 family proteins as well as poly(ADP-ribose) polymerase (PARP) cleavage were quantified to evaluate the possible factors involved in the hepatic cell death during sepsis. The apoptosis of hepatocytes under septic condition or hepatocytes treated with PKCalpha antisense was evaluated by gel electrophoresis and/or flow cytometry after Annexin-V-Fluos and propidium iodide staining. The results indicated that (1) the protein expression of membrane-associated PKCalpha was decreased at early (P < 0.05) and late (P < 0.01) sepsis; (2) the protein expressions of Bcl-2 and Bcl-xL were decreased, whereas Bax expression was increased at late sepsis; (3) the percentage of PARP cleavage was increased at early (P < 0.05) and late (P < 0.01) sepsis; (4) severe DNA fragmentation was observed at late sepsis; (5) the apoptotic cell population was increased at early and late sepsis; and (6) the percentage of apoptotic cell population in PKCalpha antisense-treated cells was significantly higher than that in untreated cells. These results suggest that inactivation of PKCalpha may play an important role in modulating hepatic apoptosis during sepsis and the apoptosis is closely associated with the alterations of Bcl-2 family proteins. PMID- 11220642 TI - A cell wall component from pathogenic and non-pathogenic gram-positive bacteria (peptidoglycan) synergises with endotoxin to cause the release of tumour necrosis factor-alpha, nitric oxide production, shock, and multiple organ injury/dysfunction in the rat. AB - The incidence of sepsis and septic shock due to gram-positive organisms has increased dramatically over the last two decades. Interestingly, many patients with sepsis/septic shock have both gram-positive and gram-negative bacteria present in the bloodstream and these polymicrobial or "mixed" infections often have a higher mortality than infection due to a single organism. The reason for this observation is unclear. The aim of this study was to investigate whether cell wall fragments from gram-positive and gram-negative bacteria could synergise to cause the release of cytokines, shock, and organ injury/ dysfunction in vivo. Male Wistar rats were anaesthetised and received an intravenous bolus of vehicle (saline), lipopolysaccharide (LPS) from Escherichia coli (0.1 mg/kg), peptidoglycan (Pep G) from Staphylococcus aureus (S10 mg/kg), co-administration of LPS (0.1 mg/kg) and PepG from S. aureus (10 mg/kg), LPS (10 mg/kg), PepG from Bacillus subtilis, or co-administration of LPS and PepG from B. subtilis. Blood pressure and heart rate were monitored for 6 h before plasma samples were taken for the measurement of TNF-alpha, total nitrite, and biochemical indices of organ injury. Peptidoglycan from both pathogenic (S. aureus) and non-pathogenic (B. subtilis) gram-positive bacteria synergised with endotoxin to cause formation of TNF-alpha, nitrite, shock, and organ injury. Synergism between PepG and LPS may partly explain the high mortality associated with mixed bacterial infections, as well as the deleterious effects of translocation of bacteria, or their cell wall components from the gut lumen in patients with sepsis. PMID- 11220643 TI - Time-frequency analysis of arterial pressure oscillations in anesthetized dogs: effects of standardized hemorrhages. AB - The purpose of this preliminary study was to investigate the advantages of the time-frequency analysis through the Continuous Wavelet Transform (CWT) compared to classical Fourier analysis using the Fast Fourier Transform (FFT) in arterial pressure signals from anesthetized mongrel dogs before and during standardized hemorrhages. Systemic arterial pressure pulsations were recorded using catheter tip manometers. CWT and FFT were applied to arterial pressure pulsations to obtain module coefficients of this transformation and its associated contours during the evolution of progressive hemorrhages, in amounts of 15, 34, and 66% of the estimated total blood volume. This mathematical analysis enabled us to identify the evolution of the frequency components of aortic valve functions, heart dynamics, respiratory influences, and vasomotor activities. Furthermore, we isolated the modulating signal of amplitude modulation phenomenon present in the arterial pressure records, as described in previous papers, being the heart rate carrier frequency. The CWT is a very sensitive and reliable procedure to analyze (time-frequency) the oscillatory phenomena in two dimensions, and to provide more information than the FFT. This new analytical procedure may provide new insights in the study of shock pathophysiology. PMID- 11220644 TI - Inhibition of inducible nitric oxide synthase (iNOS) prevents lung neutrophil deposition and damage in burned rats. AB - This study was designed to investigate the role of NO and effect of iNOS inhibitor on the lung neutrophil deposition and damage after burn. In Experiment 1, specific pathogen-free (SPF) Sprague-Dawley rats underwent 35% total body surface area (TBSA) burn. On the 4th, 8th, 16th, and 24th h after burn, blood was collected for peroxynitrite-mediated dihydrorhodamine 123 (DHR 123) oxidation assay, and lung tissues were harvested for myeloperoxidase (MPO) test and histologic study. Pulmonary microvascular dysfunction was quantitated by measuring the extravasation of Evans blue dye (EBD). In Experiment 2, S methylisothiourea (SMT) was given (7.5 mg/kg, intraperitoneal immediately post burn) to suppress iNOS activity. On the 8th h after burn, the effect of SMT on blood DHR 123 oxidation, lung MPO, lung damage, and lung iNOS expression were evaluated. Lung MPO activity increased up to a maximum of 2-fold 8 h after burn. Blood DHR 123 oxidation increased up to a maximum of 2-fold 8 h after burn. Lung permeability increased up to a maximum of 2.5-fold 4 h after burn. SMT significantly decreased lung MPO activity, blood DHR 123 oxidation, and lung permeability by 31%, 41%, and 54%, respectively. SMT markedly decreased the thermal injury-induced perivascular and interstitial inflammatory cell infiltration and iNOS staining in bronchiolar epithelium, endothelial cells, and perivascular and interstitial inflammatory cells. In conclusion, thermal injury induces blood DHR 123 oxidation, lung neutrophil deposition, lung iNOS expression, and lung damage. Peroxynitrite might play an important role in thermal injury-induced lung neutrophil deposition and damage. Specific inhibition of lung iNOS expression and blood DHR 123 oxidation with SMT on thermal injury not only attenuated the lung neutrophil deposition, but also reduced lung damage. PMID- 11220645 TI - Effects of Ringer-acetate and Ringer-dextran solutions on the microcirculation after LPS challenge: observations in the hamster cheek pouch. AB - The effects of NaCl 0.9%, Ringer-acetate, and Ringer-dextran given as intravenous infusions in the microcirculatory changes observed in early stages of endotoxemia were investigated in male hamsters treated with Escherichia coli lipopolysaccharide (LPS). The cheek pouch was studied in vivo by means of intravital microscopy. Mean arterial (MAP) and venous pressures (CVP), heart rate, mean arteriolar internal diameter, spontaneous arteriolar vasomotion (AV), red blood cell velocity (RBCV) in these vessels, and long-term effects of LPS were evaluated in animals treated with either LPS alone or the combination of LPS with NaCl 0.9%, Ringer-acetate and Ringer-dextran. The intravenous injection of LPS (0.3 mg/kg) elicited a significant reduction in MAP and CVP, cessation of AV and a decrease in RBCV. In our study, the heart rate and the arteriolar diameter did not change significantly, compared with the control values obtained before the LPS injection. No improvement in the MAP could be detected with infusions of NaCl 0.9% or Ringer-acetate but the infusion of Ringer-dextran increased it significantly. All infusions tested maintained the CVP until the end of the observation period and the Ringer-dextran increased it significantly. The heart rate was maintained around 360 beats/min with a tendency to decrease 70 min after the LPS infusion in all groups studied except the group which received NaCl 0.9% where the heart rate decreased significantly. In all the four groups, the mean arteriolar diameter did not change significantly with time during the observed period. RBCV decrease with the combination LPS + NaCl 0.9% and the infusions of Ringer-acetate and Ringer-dextran maintained it until the end of the observation period. The combination of LPS + NaCl 0.9% maintained the spontaneous arteriolar vasomotion during 50 min after LPS injection and the infusion of Ringer-acetate maintained it for the 3-h observation period. The infusion of Ringer-dextran maintained the amplitude of the spontaneous arteriolar vasomotion and increased its frequency significantly. The long-term effects of LPS showed weight loss and pus on the periorbital area. Our results suggest that the best solution to maintain the microcirculatory parameters during the early stage of endotoxemia after LPS injection was the Ringer-dextran. PMID- 11220646 TI - Base deficit development and its prognostic significance in posttrauma critical illness: an analysis by the trauma registry of the Deutsche Gesellschaft fur unfallchirurgie. AB - This prospective, multi-center, observational study of 2069 multiple trauma patients evaluated the prognostic significance of the posttrauma base deficit (BD) on hospital and intensive care unit (ICU) admission to hemodynamic changes, volume and transfusion requirements, lactate and coagulation, as well as mortality. Furthermore, the importance of the BD development throughout a patient's course of critical illness from the time of injury to ICU admission is analyzed as a prognostic factor for fatal outcome. The data were obtained by the trauma registry of the 'Deutsche Gesellschaft fur Unfallchirurgie.' The patients were subdivided into five categories of increasing BD values on hospital and ICU admission: Category I, BD < or = -2; Category II, -2 < BD < or = 2; Category III, 2 < BD < or = 6; Category IV, 6 < BD < or = 10; and Category V, BD > 10. A statistical analysis was performed by means of the ANOVA and chi-square tests. In 1264 (61.1%) of 2069 multiple trauma patients (age 39 +/- 19 years, 70.0% males, injury severity score 22 +/- 13, 18.6% mortality), the BD was documented on hospital and in 1536 (74.2%) patients on ICU admission. At both points in time, an increase in the BD category was associated with a significant decrease in systolic blood pressure and prothrombin time as well as increases in heart rate, lactate level and mortality (P < 0.0001). Also transfusion requirements (Category I: 4.5 +/- 7.7 and Category V: 13.7 +/- 13.0 packed red blood cells) increased significantly on hospital admission (P < 0.0001) with a worsening in the BD category. Mortality increased significantly (P < 0.0001) with a worsening of BD from hospital to ICU admission (from a mortality of 13% in patients with a hospital and an ICU admission BD of <6 to 45% in patients with a hospital and an ICU admission BD of >6). These data show that the base deficit is an early available important indicator to identify trauma patients with hemodynamic instability, high transfusion requirements, metabolic and coagulatory decompensation, as well as a high probability of death. The base deficit development may help to guide an early and aggressive therapy for the trauma/hemorrhage induced tissue hypoxia. PMID- 11220647 TI - Oxygen radical generation by emigrated, intra-abdominal, and circulating PMNLs during human secondary peritonitis. AB - The purpose of the study was to characterize oxygen radical generation by emigrated, intraabdominal and circulating polymorphonuclear leukocytes (ePMNLs and cPMNLs) during peritonitis, as well as to assess any differences between oxygen radical production in patients with low Mannheim peritonitis index (MPI < 26, group 1) or high Mannheim peritonitis index (MPI > or = 26, group 2). Lucigenin-enhanced chemiluminescence was used to determine spontaneous and stimulated (FMLP, PMA, and A23 187) oxygen radical generation by ePMNLs and cPMNLs. In group 1 spontaneous and stimulated oxygen radical generation by emigrated PMNLs was markedly enhanced compared to circulating PMNLs (e.g., spontaneous oxygen radical generation: 30.3 +/- 11.8 cpm/cPMNLs versus 107 +/- 46 cpm/ePMNLs, P < 0.05) . In group 2 oxygen radical generation by cPMNLs markedly increased within 48 h after diagnosis of peritonitis and surgery, contrary to radical generation by ePMNLs (e.g., A23 187-stimulated oxygen radical generation 993.7 +/- 350 cpm/cPMNLs versus 285.6 +/- 77 cpm/ePMNLs, P < 0.05. In conclusion, cPMNLs and ePMNLs exhibit marked polymorphism in their capacity to generate oxygen radicals in response to secondary peritonitis. Severe peritonitis (MPI - 26) was associated with a strong increase in oxygen radical generation by cPMNLs without a parallel activity being manifest by ePMNLs. PMID- 11220649 TI - Biomarkers in cancer chemoprevention. Workshop report. PMID- 11220648 TI - The value of immune modulating parameters in predicting the progression from peritonitis to septic shock. AB - Intra-abdominal infection is one of the major causes of septic shock and multiple organ failure. To date, what causes the disease's progression remains unclear and therefore the relevance of immune modulating therapies remains speculative. The primary outcome measure of this study was to investigate immune modulating mediators at the onset of peritonitis before the development of subsequent septic shock. The secondary outcome measure was to investigate the usefulness of these immune parameters in predicting progression from peritonitis to septic shock. Fifty-eight peritonitis patients were included in this study: 14 patients subsequently developed septic shock. All patients were examined on "diagnosis of peritonitis" (<4 h within establishment of diagnosis), during "early septic shock" (<12 h following the onset of septic shock), and once again during "late septic shock" (within 72-98 h following the onset of septic shock). The immune modulating parameters tumor necrosis factor-alpha (TNF-alpha), the soluble TNF alpha receptors I and II (sTNF-alpha RI and sTNF-alpha RII), interleukines (IL) 1beta, -6, -8, and -10, and the adhesions molecules endothelial-leukocyte adhesion-molecule (E-Selectin), intercellular-adhesion-molecule-1 (ICAM-1), and vascular-adhesion-molecule-1 (VCAM-1), in addition to nitrate and nitrite, were determined. In the peritonitis group with subsequent septic shock, TNF-alpha, sTNF-alpha RI + RII IL-1beta, IL-8, IL-10, and nitrate were significantly increased before the onset of septic shock. TNF-alpha had an area under the receiver operating characteristics curve (AUC) of 0.84 and was reliable in predicting the progression from peritonitis to septic shock. The AUC of the other immune modulating parameters, despite being significantly elevated, ranged from 0.71 to 0.76. The AUC of the conventional laboratory markers such as leukocytes and C-reactive protein ranged from 0.64 to 0.68. In peritonitis that progressed to septic shock, an early immune response had already occurred before the onset of septic shock. The progression was best predicted by TNF-alpha. Therefore, mediator therapy might be considered in high-risk peritonitis patients who show an exaggerated immune response before the progression to septic shock. PMID- 11220650 TI - Biomarkers in colorectal cancer. AB - Epidemiological studies have revealed that the major dietary constituents implicated in colorectal carcinogenesis are fat/red meat (causative) and calcium/fibre (protective). Biomarkers have been used in both animal studies and clinical trials to investigate the effect of dietary factors and chemotherapeutic agents on colon carcinogenesis. They can be used as short-term end-points when investigations based on the development of cancer are not feasible. Although they can help in elucidating dietary or pharmacological effects, important results should be confirmed with longer-term studies. Colon cancer develops through an adenoma-carcinoma sequence. The appearance of colonic polyps in individuals at risk for colon cancer has been used as an end-point in clinical trials to assess diets and pharmacological agents for their effect on colon carcinogenesis. Normal appearing mucosa can contain small foci of aberrant crypts, which can be dysplastic and thought of as microadenomas. The appearance and growth of such foci have been used to assess the effect of dietary factors and chemopreventive agents in experimental animals. Increased proliferation both increases the sensitivity of the colon to carcinogenesis and may represent an early step in colon carcinogenesis. Etheno-DNA adducts are an end-product of lipid peroxidation processes, and are strongly pro-mutagenic lesions. High dietary levels of n-6 fatty acids appear to be important here and may also increase eicosanoid or isoprostane exposure and provide a selective growth stimulus for tumour precursor cells. Low dietary calcium may lead to inhibition of apoptosis and possibly to an increase in cell proliferation. In three recently completed intervention trials, calcium moderately reduced the recurrence of adenomas, but in one study fibre increased recurrence dramatically. PMID- 11220651 TI - Intermediate effect markers for colorectal cancer. AB - Recurrence or regression of adenomatous polyps is considered to be both a biomarker of risk and an intermediate (surrogate) end-point. The observational epidemiology of adenomas resembles closely that of invasive cancer, and the findings in chemoprevention trials that have been completed closely mirror that common epidemiology. Although it is possible that both the clinical trials and the epidemiology may be wrong, these common findings suggest that adenomas in general are valid end-points. Aberrant crypt foci show promise as biomarkers, both as markers of risk and as intermediate end-points for chemoprevention trials. If issues of cost can be overcome, assessment of ras mutations in stool appears to be a promising technique for screening for large bowel neoplasms. The lack of specificity of the technique limits its utility as a sole end-point in prevention studies, however. Mucosal proliferation has been used both as a biomarker of risk and as an intermediate end-point. The utility of these measures is not clear, however, since there has been discordance between the epidemiological findings regarding proliferation and established risk factors for colorectal neoplasia. The inherent variability of the measures and the technical problems associated with their use are further impediments. However, rectal mucosal proliferation may be suitable for studies in single institutions, or in consortia with very aggressive quality control. PMID- 11220652 TI - Surrogate end-point biomarkers in chemopreventive drug development. AB - Relevant and feasible surrogate end-points are needed for the evaluation of intervention strategies against cancer and other chronic, life-threatening diseases. Carcinogenesis can be viewed as a process of progressive disorganization. This process is characterized by the accumulation of genotypic lesions and corresponding tissue and cellular abnormalities, including loss of proliferation and apoptosis controls. Potential surrogate end-points for cancer incidence include both phenotypic and genotypic biomarkers of this progression. In the US National Cancer Institute chemoprevention programme, histological modulation of a precancer (intraepithelial neoplasia) has so far been the primary phenotypic surrogate end-point in chemoprevention trials. Additionally, high priority has been given to biomarkers measuring specific and general genotypic changes correlated with the carcinogenesis progression model for the targeted cancer (e.g., progressive genomic instability as measured by loss of heterozygosity or amplification at specific microsatellite loci). Other potential surrogate end-points include proliferation and differentiation indices, specific gene and general chromosome damage, cell growth regulatory molecules, and biochemical activities (e.g., enzyme inhibition). Serum biomarkers thought to be associated with cancer progression (e.g., prostate-specific antigen) are particularly appealing surrogate end-points because of accessibility. Potentially chemopreventive effects of the test agent may also be measured (e.g., tissue and serum estrogen levels in studies of steroid aromatase inhibitors). To establish chemopreventive efficacy, prevention of virtually all biomarker lesions, or of those lesions with particular propensity for progression, may be required. Ideally, the phenotype and genotype of any new or remaining precancers in the target tissue of chemopreventive agent-treated subjects would show less, and certainly no greater, potential for progression than those of placebo-treated subjects. PMID- 11220653 TI - Susceptibility markers in colorectal cancer. AB - Many susceptibility factors contribute to an individual's risk of developing colorectal cancer. Family history of colorectal cancer (particularly with early age of onset), maleness and increasing age are all factors associated with increasing risk. About three quarters of colorectal cancers are thought to be due to somatic mutations, and both high- and low-penetrance predisposing genes contribute to the remaining quarter of cases. Many of the highly penetrant dominant genes are known, but others remain to be identified. Describing the contribution of individual genes is likely to be very complex, as some modify the impact of other genes and other environmental factors rather than incurring a direct, easily attributable effect. The two dominant predisposing syndromes are familial adenomatous polyposis and Lynch syndrome, the first due to a mutant tumour-suppressor gene APC, and the second due to mutations in a number of genes responsible for mismatch repair in DNA at cell division. Establishing genetic susceptibility for colorectal cancer will soon be possible, and could save lives by allowing targetting of screening and the encouragement of preventive behaviours. However, there will always be a risk of making healthy people "sick" through the identification of predisposing genes, and there are many potential ways by which a gene carrier may be stigmatized by society, insurance companies and employers. PMID- 11220654 TI - Endogenous hormone metabolism as an exposure marker in breast cancer chemoprevention studies. AB - There is overwhelming evidence that alterations in endogenous hormone metabolism- as a form of endogenous exposure-may be an important metabolic risk factor for the development of breast cancer. This chapter reviews current theories and major epidemiological findings that link endogenous hormones (sex steroids and their metabolites, but also insulin, and insulin-like growth factor-I (IGF-I)) to breast cancer risk. Knowledge about these metabolic risk factors can be used to identify women at increased risk of breast cancer, who might benefit most from chemoprevention. In addition, modification of high-risk endocrine profiles may itself become a central target of chemoprevention. Possible intervention strategies include improvement of insulin sensitivity, reducing concentrations of IGF-I in blood and breast tissue, reducing ovarian overproduction of androgens, inhibiting the activity of aromatase and other enzymes involved in estrogen formation within the breast, and modifying estrogen metabolism within the breast (e.g., decreasing 16alpha- and 4alpha-hydroxylation, and increasing O-methylation of catecholestrogens). Several of these possible strategies are illustrated with examples of chemopreventive agents currently in use or proposed for use to prevent breast cancer. PMID- 11220655 TI - Mammographic density as a marker of susceptibility to breast cancer: a hypothesis. AB - We propose that radiological features of breast tissue provide an index of cumulative exposure to the current and past hormonal and reproductive events that influence breast cancer incidence. The changes in breast tissue that occur with ageing, and changes in the associated radiological features of the breast, are similar to the concept of "breast tissue ageing" proposed by Pike, and may explain features of the age-specific incidence of breast cancer, both within the population and between populations. These radiological features can be observed and measured, can be related directly to risk of breast cancer, and are likely to be of value in research into the etiology of breast cancer. Identification of the sources of variation in this radiological characteristic of the breast is likely to lead to a better understanding of the factors that cause breast cancer and to new approaches to prevention of the disease. PMID- 11220656 TI - Intermediate histological effect markers for breast cancer. AB - The evidence that ductal carcinoma of the breast (DCIS) is an obligate precursor of invasive breast cancer and thus qualifies as an intermediate effect marker in chemoprevention research is reviewed. Much of the evidence on the natural history of DCIS has been derived from the era before the introduction of mammographic screening. Thus it may not be applicable in the present situation when women are likely to be under mammographic surveillance in chemoprevention trials. Further, the data that are becoming available from breast screening trials suggest that at least over follow-up periods now exceeding a decade, detection and treatment of DCIS has no impact on subsequent incidence of breast cancer. Although there are some indications that other biomarkers of malignancy are expressed similarly in DCIS and invasive cancer of similar grade, this evidence may not be sufficient to allow exclusive reliance on DCIS as an intermediate-effect marker in chemoprevention research. PMID- 11220657 TI - Inherited genetic susceptibility to breast cancer. AB - Inherited genetic susceptibility to breast cancer can be due both to genes which confer a high degree of risk and to polygenes which have a smaller effect on disease risk. An estimated 5-10% of breast cancer is considered to be due to mutations in genes conferring high risk which results in hereditary patterns of disease. Two major breast cancer susceptibility genes, BRCA1 and BRCA2, which were identified using linkage analysis in large extended breast and/or ovarian cancer pedigrees, are estimated to account for the majority of large families with breast/ovarian cancer predisposition and about two-thirds of large breast cancer families. The associated lifetime risk for breast cancer in mutation carriers ranges from 40% to 90%, depending on the extent of family history and the population. Other genetic factors, such as HRAS or CAG repeats of AR, as well as reproductive and hormonal factors may therefore modify cancer risk. Women at particularly high risk of developing breast cancer represent a group in whom expensive and rigorous screening programmes are cost-effective and who may benefit from trials of chemoprevention. There are only preliminary data on the efficacy of increased surveillance and on risk reduction due to prophylactic surgery. However, for chemoprevention to be equivalent to prophylactic mastectomy, it will be necessary to strive for an equivalent reduction. The efficacy of chemoprevention in this high-risk population is unknown. Existing and new agents for chemoprevention need to be carefully assessed in properly designed clinical trials among such women. In the process, other factors modifying the penetrance in mutation carriers need to be taken into account in order to evaluate the true effect of the chemopreventive agents. Polygenes confer much lower levels of risk and may be relevant for risk assessment when the effects of multiple loci, possibly in conjunction with environmental factors, are understood and quantified. At present, it seems unlikely that the genetic information at single polygenes will be clinically relevant for risk assessment and management. PMID- 11220658 TI - High-grade prostatic intraepithelial neoplasia as an exposure biomarker for prostate cancer chemoprevention research. AB - There is a tremendous need for exposure biomarkers, which need to function as intermediate end-points in cancer chemoprevention studies. Likely candidates include process biomarkers, atypical adenomatous hyperplasia, and a newly identified atrophic state. High-grade prostatic intraepithelial neoplasia (HGPIN) has the potential to be a useful exposure biomarker, having substantial predictive value for prostate cancer in chemoprevention trials. A limitation of the use of HGPIN as a biomarker is accessibility, since it requires the use of a highly invasive procedure that would not normally be applied unless malignancy is suspected to be present. However, most other biomarkers of prostatic tissue are similarly invasive. The HGPIN lesion appears to be highly measurable; however, problems of sampling coupled with the heterogeneity of the prostate raise questions about the degree to which the presence of HGPIN can be seen to characterize a given person's prostate gland. HGPIN has the advantage that it appears to be quite highly proximal to the development of cancer and to be modifiable. It remains less clear to what degree it reflects the exposures that are believed to alter prostate cancer risk. HGPIN has been identified as a clinical entity only recently and much additional research on the utility of this marker is needed. PMID- 11220659 TI - Intermediate biomarkers for chemoprevention of prostate cancer. AB - Use of high-grade prostatic intraepithelial neoplasia (PIN) as an intermediate biomarker for prostate cancer requires additional data concerning its natural biological behaviour. Moreover, it should be recognized that a proportion of PIN lesions may represent intraductal spread of an accompanying prostate cancer rather than a precancerous lesion. The detection rate of isolated PIN in the general population is low, and its clinical significance in the short term may be limited. Additional long-term studies on the significance of isolated PIN detected during population screening are required. Due to inadequate tissue sampling by current biopsy procedures, the presence of an accompanying prostate cancer is difficult to rule out. Endocrine therapy changes the morphology of PIN, hampering its identification by making it more closely resemble the normal benign glands. In addition, endocrine therapy may lead to molecular changes in PIN, with a potential risk of induction of resistance to endocrine therapy. Prolonged androgen deprivation (for six months) does not generally lead to eradication of PIN. Cessation of endocrine therapy is likely to lead to renewed expansion of PIN, since PIN continues to express androgen receptors and the cell-cycle protein MIB-1 under conditions of low androgen levels. Recent findings indicate that most high-grade prostate cancers seem to develop from low-grade cancers. The development of a high-grade focus of prostate cancer within a clinically latent low-grade tumour might be a suitable target for future intervention studies, provided that appropriate monitoring for development of high-grade cancer can be achieved in individual patients. PMID- 11220660 TI - The role of molecular genetics in chemoprevention studies of prostate cancer. AB - Research into the molecular genetics of prostate cancer to date has largely focused on the possible existence of one or several single-locus high-penetrance susceptibility genes and several candidate regions have been Identified, but confirmatory studies of these regions have been inconclusive. Increasingly, attention has turned to identification of candidate genes which may increase prostate cancer risk because their products play an important role in possible etiological pathways for prostate cancer. Of various such pathways which have been suggested for prostate cancer, the best studied in terms of molecular genetics is the androgen signalling pathway. Two genes in this pathway, the androgen receptor (AR) gene and the steroid 5-alpha reductase type II (SRD5A2) gene, have been under particular scrutiny and polymorphic markers in each of these genes that reproducibly predict prostate cancer risk have been identified. Such studies may have important implications for prostate cancer chemoprevention trials. As etiological pathways become better understood at the molecular level, piecing together multiple genetic variants in a pathway will allow identification of high-risk individuals and potential targets for chemopreventive interventions. Moreover, understanding the role of these genes in prostate cancer etiology may help in defining heterogeneity in response to such interventions. Finally, these genes or their products may themselves be legitimate targets for building a chemoprevention strategy. PMID- 11220662 TI - Significance of hepatic preneoplasia for cancer chemoprevention. AB - Hepatic preneoplasia represents an early stage in neoplastic development, preceding both benign and malignant neoplasia. This applies particularly to foci of altered hepatocytes (FAH), that precede the manifestation of hepatocellular adenomas and carcinomas in all species investigated. Morphological, microbiochemical and molecular biological approaches in situ have provided evidence for striking similarities in specific changes of the cellular phenotype of preneoplastic FAH emerging in experimental and human hepatocarcinogenesis, irrespective of whether this was elicited by chemicals, hormones, radiation, viruses or, in animal models, by transgenic oncogenes or Helicobacter hepaticus. Different types of FAH have been distinguished and related to three main preneoplastic hepatocellular lineages: (1) the glycogenotic-basophilic cell lineage, (2) its xenomorphic-tigroid cell variant, and (3) the amphophilic basophilic cell lineage. The predominant glycogenotic-basophilic and tigroid cell lineages develop especially after exposure to DNA-reactive chemicals, radiation, hepadnaviridae, transgenic oncogenes and local hyperinsulinism, their phenotype indicating initiation by insulin or insulinomimetic effects of the oncogenic agents. In contrast, the amphophilic cell lineage of hepatocarcinogenesis has been observed mainly after exposure of rodents to peroxisome proliferators that are not directly DNA-reactive or to hepadnaviridae, the biochemical pattern mimicking an effect of thyroid hormone, including mitochondrial proliferation and activation of mitochondrial enzymes. Hepatic preneoplastic lesions are increasingly used as end-points in carcinogenicity testing, particularly in medium-term carcinogenesis bioassays. This has been complemented more recently by the use of FAH as indicators of chemoprevention, although possible pitfalls of this approach have to be considered carefully. Our ever-increasing knowledge on the metabolic and molecular changes that characterize preneoplastic lesions and their progression to neoplasia provides a new basis for rational approaches to chemoprevention by drugs, hormones or components of the diet. PMID- 11220661 TI - Exposure biomarkers in chemoprevention studies of liver cancer. AB - Hepatocellular carcinoma (HCC) is the most common type of liver cancer, the major risk factors being hepatitis B and C viruses and aflatoxins; other factors such as alcohol are also of importance in some populations. Aflatoxin exposure biomarkers include urinary aflatoxin metabolites and aflatoxin-albumin adducts in peripheral blood. These biomarkers are well validated and have been applied in studies of many populations worldwide. They are proving to be valuable end-points in intervention studies, including chemoprevention studies. The biomarkers permit assessment of primary prevention measures to reduce aflatoxin intake. In addition, the determination of individual urinary aflatoxin metabolite profiles means that the effectiveness of chemopreventive agents designed to modulate aflatoxin metabolism can also be evaluated. Both aflatoxin-albumin adducts and urinary aflatoxin metabolites have been associated with increased HCC risk in prospective studies, indicating the predictive value of these biomarkers at the group level. However, given the multifactorial and multistep nature of HCC, it is unlikely that these exposure biomarkers will be predictive at the individual level or be of value as surrogate end-points in longer-term intervention trials aimed at reducing disease incidence. Aflatoxin-related mutations at codon 249 of the p53 gene in plasma may be more relevant in this regard but their application requires further understanding of the temporal appearance of this biomarker in relation to the natural history of the disease. PMID- 11220663 TI - Hepatocellular carcinoma: susceptibility markers. AB - Genetic polymorphisms of the carcinogen-metabolizing enzymes cytochrome P450 (CYP), glutathione S-transferase (GST) M1 and N-acetyltransferase (NAT2) as well as p53 polymorphisms have been studied experimentally as susceptibility markers for hepatocellular carcinoma development in hepatocellular carcinoma cell lines and in mouse hepatocellular carcinomas. In addition, these susceptibility markers have been studied in hepatocellular carcinoma patients, in the context of coexisting alcohol consumption, smoking and/or HBV infection. To date, there is no clear evidence that susceptibility markers have an overall impact on hepatocarcinogenesis, but in subgroups of individuals, such as smokers, susceptibility markers are emerging indicators for hepatocellular carcinoma risk definition. PMID- 11220664 TI - Carcinogen biomarkers for lung or oral cancer chemoprevention trials. AB - The potential applicability of specific carcinogen-derived biomarkers in chemoprevention trials against lung and oral cancer is discussed. At present, there are no examples of the use of these biomarkers in chemoprevention trials, but the principle has been established in chemoprevention trials directed at aflatoxin B1-induced liver cancer. Polycyclic aromatic hydrocarbons (PAHs) and tobacco-specific nitrosamines are among the most important carcinogens invoked as causes of lung and oral cancer. Biomarkers that are potentially practical for current application in chemoprevention trials are 7,8-dihydroxy-9,10-epoxy 7,8,9,10-tetrahydrobenzo[a]pyrene-DNA adducts, as determined by HPLC with fluorescence detection, nitrosamino acids in urine, 4-(methylnitrosamino)-1-(3 pyridyl)-1-butanol and its glucuronides in urine, nicotine metabolites in urine, and metabolites of cytochrome P450 substrates in urine. Biomarkers that need further development or exploration before application in trials include 7 methylguanine in DNA, tobacco-specific nitrosamine-DNA adducts, acrolein/crotonaldehyde-DNA adducts, PAH-protein adducts, acetaldehyde-protein adducts, pyrene metabolites in urine and benzo[a]pyrene metabolites in urine. Such carcinogen derived-biomarkers could be applied in chemoprevention trials to test the hypothesis that chemopreventive agents alter carcinogen metabolic activation and detoxification and, ultimately, risk for cancer. PMID- 11220665 TI - Lung cancer: chemoprevention and intermediate effect markers. AB - Even after smoking cessation, genetic damage in the airways epithelium may lead to focal progression of lung carcinogenesis. Some centres now report as many new lung cancer cases among former smokers as among current smokers. Chemoprevention is a potential approach to diminish the progression of pre-clinical genetic damage. The most intensively studied lung cancer chemoprevention agents are the retinoids, including vitamin A and its synthetic analogues and precursors. While effective in suppressing lung carcinogenesis in animal models, retinoids have failed to inhibit carcinogenesis in human chemoprevention trials with premalignant end-points (sputum atypia, bronchial metaplasia). In trials with lung cancer end-points, administration of retinoids either was ineffective or, in the case of beta-carotene, led to greater lung cancer incidence and mortality. In view of these findings, markers of specific retinoid effect (i.e., levels of RAR beta) become less relevant. Other markers of genetic instability and proliferation may be useful for both early detection and potentially as intermediate-effect markers for new chemoprevention trials. Cytological atypia, bronchial metaplasia, protein (hnRNP A2/B1) overexpression, ras oncogene activation and tumour-suppressor gene deletion, genomic instability (loss of heterozygosity, microsatellite alterations), abnormal methylation, helical CT detection of atypical adenomatous hyperplasia and fluorescent bronchoscopic detection of angiogenic squamous dysplasia offer great promise for molecular diagnosis of lung cancer far in advance of clinical presentation. These end points can now be evaluated as monitors of response to chemoprevention as potential intermediate-effect markers. PMID- 11220667 TI - Metabolic polymorphisms as susceptibility markers for lung and oral cavity cancer. AB - Lung and oral cavity cancers are causally associated with tobacco use. Alcohol is an independent risk factor for oral cavity cancer. Major classes of carcinogens present in tobacco and tobacco smoke are converted into DNA-reactive metabolites by cytochrome P450 (CYP)-related enzymes, several of which display genetic polymorphism. Individual susceptibility to cancer is likely to be modified by the genotype for enzymes involved in the activation or detoxification of carcinogens in tobacco and repair of DNA damage. Molecular epidemiological studies to assess the risk associated with metabolic polymorphisms for cancers of the lung and head and neck have shown that the overall effect of common polymorphisms is moderate in terms of penetrance and relative risk. However, some gene combinations like mutated CYP1A1/GSTM1-null genotype seem to predispose the lung and oral cavity of smokers to an even higher risk for cancer or DNA damage, although these results require confirmation in larger well defined studies that take into account the existence of ethnic variations even within the commonly defined groups. Retinoids, isothiocyanates and tea polyphenols have been identified as possible chemopreventive agents for cancers of the lung and oral cavity. While a number of trials have been conducted with retinoids or beta-carotene, the results were ambiguous and the causes are still being debated. The possible interaction of chemopreventive agents with metabolic polymorphisms as biomarkers in chemoprevention trials is discussed. PMID- 11220666 TI - Biomarkers and surrogacy: relevance to chemoprevention. AB - Clinical cancer prevention trials that use disease as the end-point are of necessity large, lengthy and costly. While such trials will always remain the 'gold standard' for establishing efficacy, they are unwieldy and inefficient for the rapid translation of our accelerating understanding of the molecular basis of cancer into preventive strategies. The inclusion of biomarkers in the process of chemopreventive agent development is crucial for the advancement of the field. This overview highlights the types of approach that are being used in the development and application of biomarkers in chemoprevention studies. Biomarkers, which measure exposure, susceptibility or risk factors, can be used in selecting study cohorts, assessing participant compliance and/or determining agent efficacy. Key features of biomarkers include reliability, precision, accuracy and validity. Not all biomarkers are suitable for all purposes and are likely to be imperfect in any single setting. Judicious selection and matching of biomarkers with agents and study cohorts is required for their effective utilization. A critical but non-dichotomous element of risk biomarkers is their degree of surrogacy. A classification scheme is provided that relates the degree of surrogacy of risk biomarkers to their utility in preventive interventions. PMID- 11220668 TI - Development of difluoromethyl-ornithine and Bowman-Birk inhibitor as chemopreventive agents by assessment of relevant biomarker modulation: some lessons learned. AB - A major goal in the development of chemopreventive agents has been to develop markers that reflect the underlying process of carcinogenesis and which are modulatable by the agent under study. An important application of such markers will be to select cohorts that are at elevated risk for cancer development, which should allow use of smaller sample sizes in definitive phase III trials as well as shorter duration (and lower cost), without loss of statistical power. Susceptibility and surrogate end-point biomarkers are particularly important in this respect. Intermediate markers are probably best assessed in terms of proportionate rather than relative risk. The systematic development of difluoromethylornithine for use in chemoprevention against human cancer has involved pilot, phase IIa and IIb trials using participants with prior colonic polyps as the study group. A unique feature of the phase IIa study was the use of a dose de-escalation design which allowed selection of the lowest effective non toxic dose of difluoromethylornithine. The phase IIb trial now in progress is using a combination of sulindac with difluoromethylornithine; the rationale for selection of markers for this study and for a randomized phase III registration trial is discussed. We also review the findings in phase I and IIa trials of Bowman-Birk inhibitor concentrate, in which patients with measurable oral leukoplakia are the study group. PMID- 11220669 TI - Selection and validation of biomarkers for chemoprevention: the contribution of epidemiology. AB - This chapter considers the epidemiological contribution of DNA adducts as an example of markers for use in chemoprevention studies, and highlights the potential biases inherent in the conduct of epidemiological studies with molecular markers. Although adducts have been interpreted mainly as biomarkers of exposure, 'bulky' DNA adducts such as those measured by 32P-postlabelling or ELISA in white blood cells are more correctly interpretable as markers of cumulative unrepaired DNA damage. The latter concept can prove useful in cancer epidemiology, since it is consistent with existing knowledge on the importance of duration of exposure in the etiology of chemically-induced cancers. Increasing evidence suggests that in addition to prolonged exposure to genotoxic chemicals, inter-individual variability in carcinogen metabolism and DNA repair is predictive of cancer risk. Also from this point of view, measurements of 'bulky' DNA adducts can be useful as biomarkers for studies in populations, since they express the amount of carcinogen linked to DNA after repair, taking into account individual repair capacity. Finally, we suggest a theory of causality based on the work of Wesley Salmon and the concept of 'propagating mark', which is particularly attractive for molecular epidemiologists. PMID- 11220670 TI - Ultraviolet radiation-induced photoproducts in human skin DNA as biomarkers of damage and its repair. AB - We have developed a 32P-postlabelling method for quantifying ultraviolet irradiation (UV)-induced cyclobutane dimers and 6-4 photoproducts in human skin in situ. We review the application of the method in studies with human volunteers, demonstrating dose-response relationships over a wide range of administered doses, repair kinetics of UV-damaged DNA among healthy individuals and melanoma patients, and modulation by sunscreens, tan and constitutive pigmentation of damage induction. A notable finding is the wide interindividual variation in DNA damage immediately after irradiation and in its repair. Moreover, the protective effects of sunscreens against erythema and DNA damage also show wide interindividual variation. These results cannot be explained by variation in the experimental methods used. The worst-case scenario is that the differences between individuals are multiplicative, resulting in 1000-fold differences in sensitivity in the population, which would be likely to translate into differences in risk of skin cancer. PMID- 11220672 TI - Genetically determined susceptibility markers in skin cancer and their application to chemoprevention. AB - Development of skin cancer is a result of interactions between genetic and environmental factors. Exposure to sunlight is an established cause of non melanoma skin cancer as well as of melanoma. Other additional factors such as exposure to environmental chemicals (e.g., chimney soot, arsenic compounds), chronic irritation of the skin, viral infections and the immune status of the host may predispose to skin cancer. The high incidence of skin cancer highlights the need for development of more effective chemopreventive agents. This requires a better understanding of genetically determined host susceptibility, which is increasingly acknowledged as a major factor in the causation of skin tumours. PMID- 11220671 TI - Intermediate-effect biomarkers in prevention of skin cancer. AB - Skin cancers, both non-melanoma and melanoma, usually progress through sequential steps towards malignant transformation, leading to mutant clones and precancerous lesions. Prevention of skin cancers relies on reduction of exposure to solar radiation and may be evaluated by measuring induction of intermediate-effect biomarkers such as sunburn cells or p53 mutations in the epidermis, actinic (solar) keratoses, UV-induced immunosuppression or naevi. Sunburn cells (apoptotic keratinocytes) and p53 mutations are indicators of UV-induced DNA lesions as early steps of malignant transformation of epidermal keratinocytes. Actinic keratoses are premalignant sun-induced skin lesions, characterized as keratinized patches with aberrant cell differentiation and proliferation; they represent risk factors for basal-cell carcinoma and melanoma and are precursors of squamous-cell carcinoma. Studies in humans have investigated UV-induced immunosuppression and its modulation by topical sunscreen application, focusing on contact hypersensitivity as measured by immunization or response to haptens, or on modulation of stimulation of allogeneic lymphocytes by epidermal cells, or local release of immunomodulatory molecules such as cis-urocanic acid or interleukin-10. Naevi are focal collections of melanocytes, usually found at the junction of the epidermis and dermis or at various depths in the dermis. Common acquired naevi arise after birth both spontaneously and in response to sun exposure. Most acquired naevi are clonal, while most melanocytes in non-naeval areas are not. Although it is not yet certain whether naevi represent premalignant lesions or risk factors, many melanomas arise in acquired naevi, and the number of naevi constitutes the best predictor of individual risk of melanoma. The presence of large (i.e., >5 mm) or atypical naevi (i.e., large naevi with non-uniform colour and irregular borders) is associated with elevated melanoma risk, independently of the number of smaller naevi. Children seem particularly vulnerable to sun-induced biological events involved in the genesis of melanoma, and the greatest increase in naevus numbers per unit of skin surface occurs before adolescence. Therefore, the distribution of naevi and their development in children are relevant to understanding melanoma occurrence in adults. PMID- 11220673 TI - Characterization and identification of Borrelia isolates as Borrelia valaisiana in Taiwan and Kinmen Islands. AB - Eleven pure cultures of Borrelia from 3 species of wild rodents (Apodemus agrarius, Mus formosanus, Rattus losea) captured in Taichung, located in the center of Taiwan island, and on Kinmen Island were characterized. Five isolates showed restriction fragment length polymorphism (RFLP) patterns of 5S-23S rRNA gene intergenic spacer sequences identical to those of strains 5MT and 10MT, identified as Borrelia valaisiana, which were isolated in the southern tip of South Korea. Although the remaining six isolates showed novel RFLP patterns, these isolates showed more similarity to members of B. valaisiana from Korea, Japan and Europe based on 16S rRNA gene and flagellin gene sequences. This led us to speculate that transmission and proliferation of this type of borrelia occurred between Taiwan and the southern part of South Korea. PMID- 11220674 TI - Acute primary infection with cytomegalovirus (CMV) in kidney transplant recipients results in the appearance of a phenotypically aberrant CD8+ T cell population. AB - Human cytomegalovirus (CMV) is a beta-herpesvirus that causes a chronic subclinical infection in healthy man. The immune system is unable to eliminate the virus completely, allowing virus to persist in a latent state. In the immunocompromised host, this equilibrium is disturbed, resulting in a clinical infection. In immunocompromised rats, clinical CMV infection is associated with an increase in NK cells and CD8+ T cells, including a phenotypically aberrant CD8+ T cell population. Using flow cytometry, we examined the effect of acute CMV infection on the composition of leukocyte subsets in immunocompromised patients. Therefore, we used peripheral blood of CMV seronegative patients receiving a kidney from a seronegative (control group) or a seropositive donor. Of the patients receiving a seropositive kidney, only the patients undergoing acute CMV infection were included (experimental group). Special attention was paid to the phenotype of the cytotoxic T cells. The development of acute CMV infection resulted in an increased NK cell number and an activation of both CD4+ and CD8+ T cells, as determined by HLA-DR expression. An aberrant CD8+ T cell subset with decreased expression of CD8 and TCR alphabeta appeared in the infected patients. Furthermore, the size of this subpopulation of CD8+ T cells is positively correlated with the viral load. PMID- 11220675 TI - A VSV-G pseudotyped HIV vector mediates efficient transduction of human pulmonary artery smooth muscle cells. AB - Attempts were made to infect human vascular smooth muscle cells derived from the pulmonary artery (hPASMC) with two different human immunodeficiency virus (HIV) vector systems. ADA/Luc or HXB2/Luc were generated by cotransfection of luciferase reporter gene vector, pNL4-3-Luc-E- R-, and one of two envelope expressing vectors, pSMADA (R5) or pSMHXB2 (X4). The VSV-G/Luc or VSV-G/GFP were produced by a three-plasmid expression system which consisted of vesicular stomatitis virus G protein (VSV-G) expressing vector, packaging plasmid, and one of two reporter genes (pHR'-CMV-Luc or pHR'-CMV-GFP). We used hPASMC, U87.CD4.CCR5 and U87.CD4.CXCR4 for infection. Neither ADA/Luc nor HXB2/Luc could infect hPASMC, though they could infect U87.CD4 with corresponding coreceptors. On the other hand, the transduction of both VSV-G/Luc and VSV-G/GFP to hPASMC was remarkable. At day 3, the relative proportion of positive cells of hPASMC infected with VSV-G/GFP was 15%. The above finding indicates a direct role of HIV 1 infection in pulmonary hypertension 'a rare complication of HIV-1 infection' and HIV-based vectors could introduce foreign genes into hPASMC for gene therapy of pulmonary hypertension. PMID- 11220676 TI - IL-12, IFN-gamma, and TNF-alpha released from mononuclear cells inhibit the spread of varicella-zoster virus at an early stage of varicella. AB - The activity of mononuclear cells to inhibit plaque formation of varicella-zoster virus (VZV) was investigated by an in vitro infectious center assay. Peripheral blood mononuclear cells (PBMC) inhibited VZV plaque formation by co-cultivation with VZV-infected fibroblasts. As compared to mononuclear cells from normal individuals, mononuclear cells from umbilical cord blood and from patients receiving corticosteroids showed a significant decrease in the ability to inhibit viral replication. This ability was significantly increased for mononuclear cells collected during the acute phase of varicella. PBMC obtained from patients in the acute phase of varicella produced significantly higher amounts of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-12 in the supernatant compared with those of healthy individuals. These data suggest that the cytokines have an important role in the inhibition of the spread of VZV at an early stage of varicella. Th1 type adaptive immunity might play a major role in VZV infection. PMID- 11220677 TI - Circulating soluble CD4 directly prevents host resistance and delayed-type hypersensitivity response to Cryptococcus neoformans in mice. AB - In the present study, we examined the effect of soluble CD4 (sCD4) on host resistance and delayed-type hypersensitivity (DTH) response to Cryptococcus neoformans using a novel mutant mouse that exhibits a defect in the expression of membrane-bound CD4 but secretes high levels of sCD4 in the serum. In these mice, host resistance to this pathogen was impaired as indicated by an increased number of live pathogens in the lung. To elucidate the mechanism of immunodeficiency, three different sets of experiments were conducted. First, administration of anti CD4 mAb restored the attenuated host defense. Second, in CD4 gene-disrupted (CD4KO) mice, host resistance was not attenuated compared to control mice. Third, implantation of sCD4 gene-transfected myeloma cells rendered the CD4KO mice susceptible to this infection, while similar treatment with mock-transfected cells did not show such an effect. These results indicated that immunodeficiency in the mutant mice was attributed to the circulating sCD4 rather than to the lack of CD4+ T cells. In addition, DTH response to C. neoformans evaluated by footpad swelling was reduced in the mutant mice compared to that in the control, and the reduced response was restored by the administration of anti-CD4 mAb. Finally, serum levels of IFN-gamma, IL-12 and IL-18 in the mutant mice were significantly reduced, while there was no difference in Th2 cytokines, such as IL-4 and IL-10. Considered collectively, our results demonstrated that sCD4 could directly prevent host resistance and DTH response to C. neoformans through interference with the production of Th1-type cytokines. PMID- 11220678 TI - NK cells eliminate Cryptococcus neoformans by potentiating the fungicidal activity of macrophages rather than by directly killing them upon stimulation with IL-12 and IL-18. AB - In the present study, we examined whether natural killer (NK) cells have direct fungicidal activity against Cryptococcus neoformans. Splenic NK cells were obtained from SCID mice and stimulated with a combination of interleukin (IL)-12 and IL-18 in flat culture plates or round tubes. They were then or at the same time cultured with the yeast cells and the number of viable yeast cells was examined. We could not detect direct fungicidal activity by NK cells under any culture condition, although they produced a large amount of IFN-gamma and exerted marked cytotoxic activity against YAC-1 cells. On the other hand, NK cells significantly potentiated the nitric oxide-mediated cryptococcocidal activity of thioglycolate-elicited peritoneal macrophages obtained from SCID mice upon stimulation with IL-12 and IL-18. The culture supernatants of NK cells stimulated with IL-12 and IL-18 provided similar results when used in place of NK cells. The induction of macrophage anticryptococcal activity by NK cells and NK cell culture supernatants were both mediated by IFN-gamma because the specific mAb almost completely abrogated such effect. Considered collectively, our results suggested that NK cells may play a regulatory role in potentiating macrophage-mediated fungicidal mechanisms in host resistance to infection with C. neoformans rather than exerting a direct killing activity against the fungal pathogen. PMID- 11220679 TI - Molecular cloning of rat NK target structure--the possibility of CD44 involvement in NK cell-mediated lysis. AB - The nature of target molecules of natural killer (NK) cell-mediated lysis remains to be elucidated. As we previously reported, mAb 109 recognizes one of the tumor associated antigens, designated as 109 antigen (Ag), expressed on the cell surface of rat fibrosarcomas W31 and W14, which are transformants of WFB (rat fetal fibroblast cell line) with H-ras oncogene. 109Ag was thought to be a target structure of NK cells since mAb 109 inhibited NK cell-mediated lysis against W31 and W14. Here, we demonstrate by molecular cloning that 109Ag is identical to rat CD44. Immunoprecipitation and immunoblotting studies also showed that mAb 109 and anti-rat CD44 mAb OX-50 recognize the same protein of W31 cell lysates with an 86 kDa molecular size. CD44 was suggested to be a target structure of NK cell mediated lysis; however, rat CD44 cDNA transfection alone into CD44 null cell lines did not result in up-regulation of target cell susceptibility to NK cell mediated lysis. Our results therefore indicated that CD44 may play a crucial role as one of the target structures in our rat fibrosarcoma system though the cell surface expression of CD44 alone does not affect NK susceptibility of the target cells. PMID- 11220680 TI - Apoptosis observed in murine peritoneal macrophages treated with interferon gamma through staphylococcal enterotoxin-dependent cell-mediated cytotoxicity. AB - The concept of superantigens is well-known and widely accepted. In this brief communication, we analyze the behaviour of antigen-presenting cells after T-cell activation by staphylococcal enterotoxin B, a representative superantigen. We tried to activate murine T cells by inflammatory mouse peritoneal macrophage in the presence of staphylococcal enterotoxin B, but no T-cell activation was observed. We, therefore, analyzed surface-specific antigens of the macrophages. They expressed insufficient amounts of MHC class II, CD80 and CD86 molecules on the surface of the cells. On the contrary, increased amounts of MHC class II and CD86 molecules on the cell surfaces were observed after incubation with interferon gamma. Interferon gamma-primed macrophages were found to be competent to activate T cells in the presence of staphylococcal enterotoxin B. To our surprise, these macrophages underwent apoptosis in parallel with T-cell activation. PMID- 11220682 TI - Size conversion of a linear plasmid in the relapsing fever agent Borrelia duttonii. AB - Borreliae have genomes composed of both linear and circular replicons. We have characterized the organization of linear DNA molecules from the Borrelia duttonii strain Ly. It contains a linear one megabase chromosome and 12 linear plasmids of 11 to 200 kb in size. A variant of the strain obtained after successive in vitro cultivation in BSKII medium had a 69 kb molecule instead of the 44 kb linear plasmid. No detectable differences in the growth rates and cellular structures were found. Southern hybridization using the vsp33 gene sequence from Borrelia hermsii as a probe showed that both plasmids (69 and 44 kb molecules) contained a similar part of the sequence. The spirochetes of the parental strain cause erythrocytes to aggregate in mice blood, but the variant did not form such aggregates and seemed to have lost its infectivity in mice. Size conversion of the linear plasmid may be associated with the host-parasite relationship in mammals. PMID- 11220681 TI - A simple and rapid method for purifying staphylococcal exfoliative toxin A. AB - A rapid and efficient method of purification of staphylococcal exfoliative toxin A, the causative agent of staphylococcal scalded skin syndrome (SSSS), has been developed. It is based on ammonium sulfate precipitation of the culture supernatant and hydrophobic interaction chromatography on Phenyl-Sepharose CL-4B. This procedure results in 87-fold purification of this toxin, which appears as a single band in sodium dodecyl sulfate-polyacrylamide gels. PMID- 11220683 TI - High-dose corticosteroid administration induces increase of serum macrophage migration inhibitory factor in patients with Vogt-Koyanagi-Harada's disease. AB - To investigate the influence of corticosteroid administration on the serum level of macrophage migration inhibitory factor (MIF), sera obtained from 9 patients with Vogt-Koyanagi-Harada's disease who had been treated with high-dose corticosteroid were analyzed. The serum MIF levels of most patients were prominently increased on day 7 and/or day 14 after corticosteroid treatment. No TNF-alpha was detected in the sera. The average serum MIF level of nine patients at the highest stages after corticosteroid administration was significantly higher than that before the corticosteroid treatment. It seems that MIF is a unique cytokine and acts together with corticosteroid to regulate inflammation and immunity. PMID- 11220685 TI - IL-4 is required for defense against mycobacterial infection. AB - Although the involvement of T helper (Th1) cells is central to protection against intracellular bacteria, including Mycobacterium tuberculosis, the involvement of Th2 cells, characterized by potent interleukin (IL)-4 secretion in mycobacterial infection is still unclear. In order to clarify the role of IL-4 in murine tuberculosis, IL-4-deficient mutant mice, IL-4 knockout (IL-4 KO) mice, were utilized. The mice were infected with H37Rv, Kurono or BCG Pasteur via an airborne infection route by placing them in the exposure chamber of a Middlebrook airborne infection apparatus. Their capacity to control mycobacterial growth, granuloma formation, cytokine secretion, and nitric oxide (NO) production were examined. These mice developed large granulomas, but not necrotic lesions in the lungs, liver or spleen (P<0.05). This was consistent with a significant increase in lung colony-forming units (CFU). Compared with levels in wild-type mice, upon stimulation with mycobacteria, splenic IL-10 levels were low and IL-6 levels were intermediate, but interferon (IFN)-gamma and IL-12 levels were significantly higher. IL-18 levels were within the normal range. The level of NO production by alveolar macrophages of the IL-4 KO mice was similar to that of the wild-type mice. Granulomatous lesion development by IL-4 KO mice was inhibited significantly by treatment with exogenous recombinant IL-4. These findings were not specific to the IL-4 KO mice used. Our data show that IL-4 may play a protective role in defense against mycobacteria, although IFN-gamma and TNF-alpha play major roles in it. Our data do not rule out an IFN-gamma-independent function of IL-4 in controlling tuberculosis. PMID- 11220684 TI - Characterization of Vibrio parahaemolyticus manganese-resistant mutants in reference to the function of the ferric uptake regulatory protein. AB - In many bacteria, the ferric uptake regulatory protein (Fur) has a central role in the negative regulation of genes affected by iron limitation. In this study, Vibrio parahaemolyticus strains carrying mutations in the fur gene encoding Fur were isolated by the manganese selection method to assess the function of Fur in connection with alternations in the coordinate expression of the siderophore vibrioferrin (VF) and iron-repressible outer membrane proteins (IROMPs). Ten out of 25 manganese-resistant mutants constitutively produced VF and expressed at least two IROMPs irrespective of the iron concentration in the medium. PCR-direct DNA sequencing of the fur genes in these mutants identified four different point mutations causing amino acid changes. Moreover, a fur overexpressing plasmid was constructed to prepare antiserum against V. parahaemolyticus Fur. Western blotting with this antiserum revealed that the intracellular abundance of the wild-type Fur was not significantly affected by the iron concentrations in the growth medium, and that the Fur proteins of the mutant strains occurred at substantially smaller amounts and/or migrated more rapidly in sodium dodecyl sulfate-polyacrylamide gel electrophoresis than the wild-type Fur. These data afford an additional insight into the structure-function relationship of Fur and imply its involvement in the iron acquisition systems of V. parahaemolyticus, although it is yet unknown whether its action on the target genes is direct or indirect. PMID- 11220686 TI - Serological properties of Abiotrophia and Granulicatella species (nutritionally variant streptococci). AB - Serological variations were examined among 12 type or reference strains and 91 oral isolates of vitamin B6-dependent Abiotrophia and Granulicatella spp. Rabbits were immunized with whole cells of 12 selected strains and 10 typing antisera were obtained, which were unreactive with the Lancefield group A to G antigen preparations. The reactivity of the antisera and autoclaved cell surface antigen extracts was tested by double diffusion in agar gel and a capillary precipitin test. These typing antisera categorized all Abiotrophia defectiva strains, all except one Granulicatella elegans strain, three-quarters of the Granulicatella adiacens, and half of the Granulicatella paraadiacens into 8 serotypes and 2 subserotypes. The Granulicatella balaenopterae type strain was unserotypable. All A. defectiva strains were serotype I, some of which were divided into subserotype I-1 and/or I-5. The G. adiacens strains generally belonged to serotype II or III, and the G. paraadiacens strains to serotype IV, V or VI. All G. adiacens or G. paraadiacens serotype II strains were also subserotype I-5. The G. elegans strains were serotype VII or VIII. These Abiotrophia and Granulicatella serotypes were undetectable among 33 strains of the other 11 species including the bacteriolytic enzyme-producing but vitamin B6-independent strains of Streptococcus, Enterococcus, Dolosigranulum and Aerococcus. The proposed serotyping system for Abiotrophia and Granulicatella spp. would be helpful in the identification and classification of these unique coccal isolates in ecological and epidemiological studies. PMID- 11220687 TI - Salmonella typhimurium induces apoptosis in human monocyte-derived macrophages. AB - Salmonella species represent a leading cause of gastroenteritis worldwide. More recently, they have been proposed as putative vaccine delivery vehicles in humans. Oral infection with Salmonella leads to invasion of the intestinal epithelial barrier and subsequent interaction with mucosal macrophages. In this study, we investigated the fate of Salmonella typhimurium-infected human macrophages differentiated from blood monocytes by GM-CSF. Wild type S. typhimurium strain SL1344 induced macrophage surface blebbing and caused the release of host cytoplasmic lactate dehydrogenase beginning 30 min post infection. Three hours later more than 80% of the macrophages in the culture were killed. In contrast, during the same period, macrophages infected with the non invasive S. typhimurium strain BJ66 remained viable. Chromatin fragmentation is a hallmark of cells undergoing apoptosis. Using TUNEL analysis, we observed chromatin fragmentation in macrophages infected with SL1344 but not in BJ66 infected cells. Consistent with this observation, we found that pretreatment of human macrophages with an inhibitor of caspase-3, a member of the pro-apoptotic enzyme family shown to be involved in S. typhimurium-induced killing of mouse macrophages, reduced SL1344-mediated cytotoxicity by 40%. Our study provides the first evidence that invasive S. typhimurium induces apoptosis in human macrophages that were differentiated from blood monocytes by GM-CSF, and that cell death is a caspase-dependent phenomenon. PMID- 11220688 TI - Effect of sulbactam on anti-pseudomonal activity of beta-lactam antibiotics in cells producing various levels of the MexAB-OprM efflux pump and beta-lactamase. AB - The beta-lactamase inhibitor, sulbactam, was tested for beta-lactamase inhibitory activity in Pseudomonas aeruginosa cells producing various levels of both the MexAB-OprM efflux pump and beta-lactamase. We found that sulbactam lowered the MICs of cefoperazone and piperacillin by inhibiting the beta-lactamase 8-fold in the cell producing a constitutively high level of AmpC-type beta-lactamase and a wild-type level of MexAB-OprM pump compared with that without sulbactam. The MICs of cefoperazone and piperacillin in the cell producing a constitutively high level of both the efflux pump and beta-lactamase under the presence of sulbactam were 8 and 4 times, respectively, lower than that without sulbactam. The MICs of sulbactam in the cell producing a constitutively high and a wild-type level of the efflux pump were 16- and 8-fold higher, respectively, than that in the mutant lacking the efflux pump. We concluded that sulbactam exerts potent beta-lactamase inhibitory activity in the cell producing a high level of efflux pump, in spite of the fact that sulbactam serves as a substrate of the MexAB-OprM pump. Increasing amounts of sulbactam over the weight of beta-lactams further strengthen the effect of beta-lactam antibiotics. PMID- 11220689 TI - Early ontogenic disturbances in cell migration in mentally disabled adult. AB - Disturbances in cell migration are heterogenic disorders of brain development commonly associated with epilepsy and mental retardation. We report a 45-year-old oligophrenic man with defect of lower limbs and family history of mental retardation who died because of brainstem hemorrhage. At post-mortem and histopathological examination, complex brain malformation characterized by bilateral periventricular heterotopia, cortical dysgenesia, partial agenesia of corpus callosum and thin-walled blood vessels was found. Immunohistochemical examination revealed the presence of fibronectin, collagen IV and laminin in wall of pathological vessels. Cyclooxygenase-2 (COX-2) expression in neurons within heterotopias and dysgenic cortex was negative. It may indicate their maturity and indirectly, normal activity of postsynaptic NMDA receptors that explains absence of epileptic attacks in our patient. The presence of COX-2-negative neurons and compounds of basal lamina in fetal-like vessels within heterotopias and dysgenic cortex, suggests that these probably initially immature structures became mature during 45 years of patient's life. PMID- 11220690 TI - Does PRNP gene control the clinical and pathological phenotype of human spongiform transmissible encephalopathies? AB - BACKGROUND: Human spongiform transmissible encephalopathies (TSE) are a group of neurodegenerative diseases caused by a transmissible not yet recognized agent; their distinctive neuropathological features are astrocytosis, spongiform lesions of the neuropil, neuronal loss and occasionally amyloid plaques in the cortical and subcortical gray matter. TSE are biochemically characterized by the deposition in the nervous system of an amyloid-type protein, PrPres derived from the post-translational modification of a normal protein, PrPsen. The expression of this protein is controlled by the PRNP gene mapped on chromosome 20 in man. A number of point mutations of the PRNP gene have been described in the familial forms of these TSE. Some of these mutations have been associated with differences in the phenotypic expression of the disease. MATERIAL AND METHODS: This study was designed to verify whether it was possible to identify a selective phenotype depending upon a given PRNP modified genotye; for this purpose, a group of familial TSE cases (CJD 210ILE, CJD 201LYS, FFI 178ASN) were selected and their neuropathological profiles have been compared with those of a large series of sporadic CJD cases. RESULTS: No significant differences were found between the topography and severity of lesions in the cerebral cortex, cerebellum, hippocampus, basal ganglia and thalamus between the two groups. Two differences were found: the clinical duration of the disease which appeared significantly (p = 0.02) shorter in the 210ILE-mutated cases compared to that of non-mutated sporadic cases. The highly selective vulnerability of thalamus in FFI showing a severe pathology especially in its dorso-medial part in comparison with that of the sporadic CJD cases. CONCLUSION: The results of this study confirm that the different polymorphism at codon 129 of the PRNP gene, which could be involved in the structural "domains" of human PrP, might modulate the pathological phenotype of TSE. PMID- 11220691 TI - A contemporary case of encephalitis lethargica. AB - We present a clinicopathological report of a recent fatal case of a 27-year-old woman whom we consider to have had encephalitis lethargica. Clinical features of note were a presentation with vertigo, persistent vomiting and sleep disturbance including marked daytime somnolence and vivid nightmares. On examination, she had impaired slow pursuit vertical eye movements, dysarthria, an expressionless face and slow tongue movements. She went on to develop gross supranuclear gaze palsy, neck rigidity, bradykinesia, blepharospasm, profound somnolence and anarthria but no tremor, weakness or impairment of cognition. She died after an illness lasting 12 months. On investigation, the cerebrospinal fluid was found to contain a very high level of IgG with oligoclonal bands but no cells. Post-mortem examination revealed an active encephalitis, mainly centered on the upper brainstem and diencephalon with extensive Purkinje cell loss and marked plasma cell infiltrates and morula cells. No virus was recovered. PMID- 11220692 TI - Expression of matrix metalloproteinases in a series of 12 meningiomas. AB - The expression of metalloproteinases was evaluated in a series of 12 meningiomas of various histological subtypes including 3 meningotheliomatous, 3 fibroblastic, 4 transitional and one psammomatous meningioma (WHO grade I) as well as one anaplastic meningioma (WHO grade III). No gelatinolytic activity could be detected in all tumor samples pointing towards no or very low activity of both MMP-2 and MMP-9. At least MMP-2 mRNA could be found in 10 out of 12 tumor samples by the reverse transcription PCR method (RT-PCR) followed by electrophoresis on silver-stained polyacrylamide gels, which allows the detection even of small traces of a specific mRNA. The PCR products were identified as MMP-2 sequences without introns (mRNA-derived) by direct sequencing, thereby demonstrating a low transcriptional activity of the gene. The translation of these mRNAs, however, did not result in amounts of protein detectable by immunohistochemistry or Western blotting. Therefore, neither MMP-2 nor MMP-9 should play a major role for tumor growth within dura mater or bone structures or for brain infiltration in our tumor series. Therefore, other mechanisms must be responsible for extracellular matrix degradation at least in a fraction of meningiomas. PMID- 11220694 TI - Pseudogliomatous growth pattern of anaplastic small cell carcinomas metastatic to the brain. AB - Carcinomas metastatic to the brain usually grow very well circumscribed, with sharp delineation. Radiosurgery takes advantage of this fact by using the gamma knife for definitive treatment of small metastases. We report a systematic study of the growth pattern of cerebral metastases, focusing on tumor delineation. In 26 cases of 66 metastatic anaplastic small cell carcinomas and in one case of adenocarcinoma, we observed poorly defined borders and a highly diffuse pattern of invasion. Infiltrating carcinoma cells changed to an elongated shape adapting to preexisting tissue structures. This pseudogliomatous growth pattern of some brain metastases--apparently most likely in neuroendocrine carcinomas--is of potential importance for therapeutic strategies in the treatment of brain metastases, especially when considering treatment with radiosurgery and gamma knife. PMID- 11220693 TI - Supratentorial giant cell ependymoma. AB - Ependymomas account for 3 to 9% of all neuroepithelial tumors and, although occurring most often within the ventricular system, they may arise from the extraventricular parenchyma as well. Several histologic patterns of these neoplasm are well known, but little attention has been devoted to a variant composed of giant elements. We describe the case of a 13-year-old girl experiencing a 3-month history of partial seizures in whom cranial magnetic resonance imaging showed an extraventricular, right parietotemporal neoplasm, adherent to the overlying dura mater. Histologic, immunohistochemical and ultrastructural findings were consistent with those of a high-grade ependymoma. The tumor was characterized by the presence of a major component of pleomorphic giant cells, as also seen in pleomorphic xantoastrocytoma, subependymal giant cell astrocytoma and glioblastoma multiforme. Similar elements have been described in two filum terminale and one supratentorial, intraventricular ependymoma, respectively. Histologic and evolutional data of those and of our own case suggest that isolated giant cells are not necessarily linked to a bad prognosis in ependymomas. PMID- 11220695 TI - Primary intracerebral malignant melanoma with leptomeningeal spread, extradural extension and lung metastasis. AB - A rare primary intracerebral solitary malignant melanoma with extracranial metastasis is reported. The patient was a 66-year-old man who was revealed to have a tumor in the right temporal lobe by MRI. The tumor was totally resected and the histopathological diagnosis was malignant melanoma. Despite postoperative treatment with chemo-radiotherapy, tumor recurred with multiple subarachnoid dissemination. Complete autopsy showed marked leptomeningeal dissemination of tumor in the cerebro-spinal compartment. In the outside of the central nervous system, a microscopic metastatic nodule was found in the right lung. Metastatic tumor in the spinal cord showed the extradural extension which might have led to hematogenous metastasis to the lung. PMID- 11220696 TI - A case of frontotemporal dementia and parkinsonism of early onset with progressive supranuclear palsy-like features. AB - We report a patient with frontotemporal degeneration and parkinsonism with mental retardation. The patient was a 54-year-old man who had parkinsonism that resembled progressive supranuclear palsy, frontotemporal degeneration and myoclonus. His family included many affected members. Neuropathologically, there was degeneration of the frontal and temporal cortices, the basal ganglia, the brainstem and the cerebellum. Microscopically, neuronal loss was severe in the frontal and temporal cortex, the globus pallidus, substantia nigra, red nucleus and dentate nucleus. Fibrillary changes were found in neurons and glia that were immunostained for tau. Although we could not define the genetic abnormalities, we thought that this case might have involved frontotemporal dementia and parkinsonism linked to chromosome 17. PMID- 11220697 TI - Breakage of insulin syringe needle in subcutaneous tissue. AB - We report the case of a young girl with diabetes mellitus whose insulin syringe needle broke and became embedded in subcutaneous tissue. PMID- 11220698 TI - Deletion of the long arm of the Y chromosome in an adolescent with short stature and hypogonadism. AB - We describe a patient with short stature more than that expected for non-treated congenital adrenal hyperplasia due to nonclassic 21-hydroxylase deficiency with deletions in the long arm of the Y chromosome including the CGY gene and the AZF subregions. PMID- 11220699 TI - Bilateral galactocele in a male infant: a rare cause of gynecomastia in childhood. AB - A galactocele is a rare benign breast lesion usually occurring in females during or following lactation. These lesions are a rare cause of breast enlargement in infants and children. In this article we present a 10 month-old boy who was admitted with a two-month history of bilateral progressive breast enlargement, and diagnosed as having galactocele. Our purpose was to emphasize the importance of galactocele as a benign condition in the differential diagnosis of gynecomastia in childhood. PMID- 11220700 TI - Present status of the use of growth hormone in short children with bone diseases (diseases of the skeleton). AB - Skeletal dysplasias are genetic disorders of bone and cartilage development, mainly characterized by disproportionate short stature. Achondroplasia is the commonest and best described form of skeletal dysplasia, leading to a mean final height of 131+/-5.6 cm for males and 124+/-5.9 cm for females. Growth hormone (GH) has been used in different studies in patients with achondroplasia in order to ameliorate their height, and short term results range from rather positive to moderate. However, disproportionate advancement of bone age has been observed that can compromise the positive effect of such treatment. Furthermore, concern exists about the aggravation of body disproportion necessitating a later leg lengthening procedure in order to achieve proportionate adult stature. In hypochondroplasia, GH treatment seems to give better results when administered at puberty. No data on final height yet exist, however, so that more studies with greater numbers of patients need to be performed before a consensus on GH use in achondroplasia and hypochondroplasia can be reached. Other forms of skeletal dysplasias are quite rare, so that no conclusion on GH use in such patients can be drawn. Finally, in osteogenesis imperfecta, GH administration significantly ameliorates bone density but does not clearly seem to affect final height positively. PMID- 11220701 TI - Molecular characterization of mutations in Indian children with congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency. AB - Congenital adrenal hyperplasia (CAH) is the commonest cause of female pseudohermaphroditism. It is most often due to steroid 21-hydroxylase deficiency resulting from mutations in the CYP21 gene. This study was conducted to characterize mutations in the CYP21 gene, determine their frequency and correlate genotype with phenotype in Indian children with CAH. Twenty-eight patients with salt-wasting (SW) or simple-virilizing (SV) forms of the disease as well as parents and siblings were studied. Allele specific PCR was carried out and rapid characterization of six mutations was achieved in 23 patients. Twelve patients were homozygous for the mutations and 11 were heterozygous, of whom eight were compound heterozygotes and three were hemizygotes; no mutation was found in five patients. The homozygosity of the mutations was found to be high in our population. The most common mutation was Ile173Asn (31.8%), followed by intron2 splice (27.2%), Gln319stop (22.7%), gene deletion (15.9%) and Pro31Leu (2.2%). Genotype-phenotype correlations showed that the most frequent mutations in the SW group were intron2 splice and Gln319stop mutations (33.3% each) and Ile173Asn (71.4%) in the SV group. PMID- 11220703 TI - IGF-I resistance and Turner's syndrome. AB - The pathogenesis of growth failure in Turner's syndrome is not clear but might be attributed to a decreased sensitivity to insulin-like growth factor-I (IGF-I) in distinct cell lines or to its reduced autocrine/paracrine action. Growth hormone (GH) therapy leads to increments in IGF-I levels and to growth acceleration. In order to evaluate the pattern of overcoming IGF-I resistance through childhood and adolescence, we measured IGF-I in 78 girls with Turner's syndrome aged 4.6 18.3 years on 160 occasions without or during GH (1 IU/kg/week [0.33 mg/kg/week]) or GH+estradiol (E2) therapy and compared them with local IGF-I standards. In untreated patients, IGF-I levels were low normal (-0.71+/-0.18 SDS, mean +/- SEM). In both GH or GH+E2 treated girls, circulating IGF-I levels were persistently supraphysiological (GH only: +3.61+/-0.23 SDS; GH + estradiol: +3.18+/-0.31 SDS). The age-dependent pattern of IGF-I secretion was conserved but the pubertal increase occurred earlier. The highest standardized IGF-I levels were observed at age 8.5-9.4 years (+6.62+/-1.00 SDS) and 9.5-10.4 years (+5.61+/ 1.03 SDS). GH+E2 substitution had no additional effect on circulating IGF-I. We conclude that high IGF-I levels are needed to overcome the IGF-resistance in Turner's syndrome. They reflect the action of GH therapy but not of estrogens. The earlier pubertal increase of IGF-I might be caused by exaggerated adrenal androgens. PMID- 11220702 TI - Advances in the molecular genetics of hypogonadotropic hypogonadism. AB - Mutations in several genes have been shown to cause hypogonadotropic hypogonadism (HHG) in humans. This condition may result from abnormalities in hypothalamic gonadotropin-releasing hormone (GnRH) secretion, impaired pituitary gonadotropin release, or both. Here, we consider mutations in KAL in X-linked Kallmann syndrome; DAX1 in X-linked adrenal hypoplasia congenita; the related orphan nuclear receptor, steroidogenic factor-1; leptin and prohormone convertase-1, which may influence GnRH release and processing; the GnRH receptor; the pituitary transcription factors, HESX-1, LHX3 and PROP-1; and the gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone (LH). Identifying naturally occurring mutations in these genes provides important information about the role of these factors in the development and function of the hypothalamic-pituitary gonadal axis in humans. Different approaches to treatment and counseling may be needed, depending on the condition. Furthermore, the pathophysiological basis of HHG in the majority of individuals remains unclear, despite recent advances. Other candidate genes may be involved in these patients. PMID- 11220704 TI - Seasonal variation of birth month and breastfeeding in children with diabetes mellitus. AB - OBJECTIVE: As breastfeeding is suggested to protect against diabetes mellitus we decided to investigate whether the seasonal variation of month of birth of diabetic children, with more diabetes in children born in summer, can be explained to some extent by a seasonal variation of exclusive breastfeeding. PATIENTS: A population-based group of 297 children who had been diagnosed with diabetes mellitus before the age of 15 years was compared with 792 matched healthy subjects. RESULTS: There was no difference in duration of breast-feeding between children who later got diabetes and the controls. Children (both diabetics and controls) born during the summer were exclusively breastfed for a mean period of 2.2 months. Corresponding figures for children born during winter were 2.8 months (p<0.04), spring 2.5 months (n.s.) and autumn 2.7 months (p<0.05). Seasonality was most pronounced in children who developed diabetes between the ages of 10 and 15 years. CONCLUSION: These results indicate that children born during the summer, who have increased risk of developing diabetes mellitus, have also been exclusively breastfed for a shorter time. PMID- 11220705 TI - Seasonality of birth in children (0-14 years) with type 1 diabetes mellitus in Slovenia. AB - The aim of this study was to find out whether there is seasonality of month of birth of children with diabetes in Slovenia and if so whether it differs from that of the general population. A cohort of 849 children and adolescents (0-14 years) with type 1 diabetes mellitus born between 1956 and 1998 were included in the study. Monthly and seasonal patterns of birth of the patients with diabetes were compared with the pattern of normal live births (n = 1,345,921) and the pattern of disease onset. Statistical analysis was made using Student's t-test to compare the means between the four seasons of the year, and single cosinor analysis for a period of 12 months. The children and adolescents with diabetes had a statistically significant different seasonality of month of birth compared to that of the general population, and an opposite pattern from the seasonality of month of onset of disease. The observations made are in accordance with observations made recently in other countries and support the hypothesis that a virus infection transmitted by the mother to the fetus during the annual viral epidemic induces the autoimmune process in the pancreatic beta-cells in genetically susceptible individuals who will subsequently develop clinical diabetes during childhood. PMID- 11220706 TI - Early detection of impaired glucose tolerance in patients with cystic fibrosis and predisposition factors. AB - INTRODUCTION: The number of patients with glucose tolerance alterations associated with cystic fibrosis (CF) has increased, probably due to the greater survival rate among sufferers of this disease. We studied impaired glucose tolerance (IGT) in patients with CF and investigated whether its appearance has any relationship with age, sex, genetic mutation and/or the degree of clinical involvement. We assessed the parameters that might allow early detection. PATIENTS AND METHODS: In 28 patients with CF (14 M, 14 F; aged 22 months to 18 years), sex, genetic mutation, nutritional status and the degree of pancreatic and pulmonary involvement were recorded. The metabolic study included glycosylated hemoglobin (HbA1c) determination, oral glucose tolerance test (OGTT) and intravenous glucose tolerance tests (IVGTT). RESULTS: In the patients with CF, 35.71% showed impaired glucose tolerance (IGT) and 3.57% had diabetes mellitus. The patients with IGT and CF were 3.2 years older than those with normal glucose tolerance (NGT; p<0.05), but no significant differences were found regarding sex, anthropometric measurements, percentage of pulmonary gammagraphic involvement, Shwachman-Kulczycki test or HbA1c. In the OGTT, the patients homozygous for the deltaF508 mutation had higher blood glucose values than the heterozygous group (p=0.03), but these values were not higher than those in patients with other mutations. During the OGTT, blood insulin values at 30' were reduced in patients with IGT compared to patients with NGT (p<0.02) and the insulin peak occurred at 100.9+/-24.3 min compared to 65.3+/-21.8, respectively (p<0.05). In the IVGTT, 82.14% of the patients had reduced insulin levels at 1 and 3 min (I1'+3'). No differences in the blood glucose levels during the OGTT were found between patients with normal I1'+3' values and patients with reduced values. CONCLUSIONS: A high percentage of patients with CF also present with IGT. This increases with age and is more common among patients homozygous for the deltaF508 mutation and is not related to clinical status. Alterations in the kinetics of insulin secretion play an important role in the appearance of IGT and CF. We suggest that the OGTT is a more sensitive method than IVGTT for identifying early alterations in CF-related diabetes mellitus. PMID- 11220707 TI - Real-time sonography for screening of gallbladder dysfunction in children with type 1 diabetes mellitus. AB - The aim of this study was to evaluate the occurrence of gallbladder dysfunction in children with type 1 diabetes mellitus using real-time ultrasonography. The study population consisted of 20 diabetic children (11 male, 9 female; age 11.7+/ 2.8 years; diabetes duration 0.5-7 years) with clinically negative neuropathy findings and 15 healthy controls (11 male, 4 female; age 10.5+/-3.7 years). Three dimensional measurements of the gallbladder were made before and 15, 30, 45, 60 min after intake of diet chocolate. Gallbladder volumes were calculated by the ellipsoid formula. Fasting gallbladder volume of diabetic children (16.9+/-9.5 ml) was significantly greater than that of the controls (10.6+/-5.3 ml; p=0.017). Ejection fraction and maximal contraction showed no significant difference between the two groups. Diabetic patients with multiple microvascular complications had diminished gallbladder motility. There was a negative correlation between BMI and maximal contraction (p<0.05). Nerve conduction velocity was diminished in 45% of the diabetic patients. In conclusion, gallbladder function is preserved in pediatric type 1 diabetic patients with a disease duration less then 10 years, but dilated gallbladder at rest may be an early sign of gastrointestinal autonomic neuropathy and a risk factor for gallstone formation. PMID- 11220708 TI - Celiac disease and short stature--not always cause and effect. AB - Four children with familial short stature were diagnosed with celiac disease (CD) by positive serology for antigliadin and antiendomysial antibodies and characteristic intestinal biopsy findings. These patients complied well with their diet as evidenced by their parents' reports, increase in weight standard deviation scores in all but one child, and reversion to seronegativity for antigliadin and antiendomysial antibodies in all four. However, typical catch-up for linear growth did not occur. In our view, the poor response of linear growth is evidence that the original stunting was not due to CD. Since the advent of sensitive tests for antiendomysial antibodies, many asymptomatic children have been diagnosed as having CD. Some of these children are short and despite a history of familial short stature their growth stunting may be wrongly attributed to CD. This report highlights this new problem and emphasizes the need for caution when predicting growth response to a gluten-free diet. PMID- 11220709 TI - High-impact loading training induces bone hyperresorption activity in young elite female gymnasts. AB - The aim of this study was to investigate the effect of intensive exercise on bone turnover (as reflected by bone resorption) in young elite female gymnasts. Forty five healthy girls including 24 gymnasts (11.9+/-2 yr) and 21 controls (12.3+/ 1.4 yr) were studied. Body weight, height, bone age and body composition were measured. Bone mineral density (BMD) was assessed at the whole body, lumbar vertebrae, hip and radius by means of DXA. Volumetric density (BMAD) was calculated. Bone velocity (SOS) and attenuation (BUA) were measured by QUS at the calcaneus. Urinary androstenedione (delta4), dehydroepiandrosterone sulfate (DHEA S), and CrossLaps (CTx) were measured. BMD and BMAD were significantly greater in the gymnasts at all sites except whole body. SOS was found significantly higher. Delta4 values were significantly lower in the gymnasts. The distribution of the subjects according to Tanner stages was not different between groups. CTx levels were significantly higher in the gymnasts (989.08+/-154.63 microg/mmol Cr.) vs controls (580.25+/-123.99 microg/mmol Cr., p=0.02). CTx values decreased from Tanner stage 1 to stage 4 in each group, the gymnasts' levels always being higher than those of the controls. In conclusion, gymnastics seems to stimulate bone resorption activity in highly-trained young females. The coexistence of bone hyperresorption and higher BMD in gymnasts suggests increased bone turnover resulting in increased bone density in these subjects. PMID- 11220710 TI - The influence of weight loss on fibrinolytic and metabolic parameters in obese children and adolescents. AB - We studied i) whether short-term weight loss alters plasminogen activator inhibitor-1 antigen (PAI-1-Ag) and tissue-type plasminogen activator antigen (tPA Ag) in obese children, and ii) whether changes in body composition and/or abdominal adiposity are responsible for changes in PAI-1 and tPA-Ag. 20 obese boys (mean age 11.9 yr) and 40 obese girls (mean age 12 yr) were studied before and after three weeks of low-caloric diet and physical activity. Body composition was assessed by means of bioelectrical impedance, and the waist-to-hip ratio (WHR) was measured. Blood samples were determined for insulin, glucose, triglycerides, PAI-1-Ag, tPA-Ag, and the fasting insulin resistance index (FIRI) was calculated. Boys had a greater WHR, higher levels of glucose, and a slightly greater FIRI than girls. Estimates of adiposity, insulin, and triglycerides were correlated with PAI-1 and tPA-Ag. WHR was significantly correlated with fibrinolytic parameters only in girls. Insulin and tPA-Ag contributed to PAI-1 (adj. R2 = 0.36, p <0.0001), whereas percentage fat mass and triglycerides contributed to tPA-Ag (adj. R2 = 0.469, p <0.0001). The weight loss program significantly reduced adiposity, abdominal adiposity, and lowered fibrinolytic and metabolic parameters. Initial levels of PAI-1 and changes in body mass contributed to the fall in PAI-1 (adj. R2 = 0.18, p = 0.0016) and initial levels of tPA-Ag contributed significantly to changes in tPA-Ag (adj. R2 = 0.57, p <0.0001). The results suggest that changes in fibrinolytic parameters are associated with the loss in body mass but can occur independently of a concomitant reduction in fatness. Although initial PAI-1 and tPA-Ag predict the changes of these fibrinolytic parameters, the results do not exclude the possibility that the improvement in metabolic state and changes in unmeasured parameters related to physical activity and low-caloric diet could have influenced our findings. PMID- 11220712 TI - Thyroid eye disease in children and adolescents--new therapeutic approaches. PMID- 11220713 TI - "Insignificant" mechanism of injury: not to be taken lightly. AB - BACKGROUND: Trauma resources should be spent rationally. The mechanism of trauma is used extensively to triage patients to appropriate levels of care. We examine the hypothesis that patients with "insignificant" mechanism of trauma may have major injuries that require expert trauma care. STUDY DESIGN: Over 9 months at a high-volume Level I trauma center, a prospective study was done on patients who sustained ground-level falls (GLF), low-level falls (LLF) from less than 10 feet, or were found down (FD) with no external evidence of significant trauma, and required evaluation by the trauma team. Of 301 patients included, 110 (37%) had GLF, 95 (31%) LLF, and 96 (32%) FD. Our main outcomes measure was significant injuries, defined as visceral or intracranial injuries, long-bone, pelvic, facial, or spinal fractures. RESULTS: One hundred ten patients (37%) had significant injuries, 20 (7%) were admitted to the ICU, 14 (5%) required an operation, and 4 (1%) died. The most common injuries were intracranial and skeletal. Almost all patients were evaluated by CT (95%), but only one-quarter had abnormal findings on it. LLF, age more than 55 years, and the absence of severe intoxication (blood alcohol level of less than 200 mg/dL) were independent risk factors for significant injuries. A statistical prediction model showed that, when all risk factors are present, the probability of significant injuries is 73%; when all risk factors are absent, there is still a 16% chance for significant injuries. Patients with significant injuries had more operations, longer hospital stays, and higher hospitalization costs compared with patients without significant injuries. CONCLUSIONS: Low-energy trauma may produce significant injuries, predominantly intracranial and skeletal. Trauma care providers should be cautious about dismissing such patients based on the trivial mechanism of injury. Patients with LLF who are older than 55 years and not severely intoxicated have a high likelihood for significant injuries. Resources should be spent rationally for patients who do not have these characteristics, because the probability of significant injuries among them is low, but not zero. PMID- 11220711 TI - Seasonality of month of birth of children (0-14 years old) with type 1 diabetes mellitus in the District of Catania, Sicily. PMID- 11220714 TI - An evaluation of risk factors for mortality after burn trauma and the identification of gender-dependent differences in outcomes. AB - BACKGROUND: The primary objective of this study was to determine an objective method for estimating the risk of mortality after burn trauma, and secondarily, to evaluate the relationship between gender and mortality, in the setting of a quantifiable inflammatory stimulus. Previously reported estimates of mortality risk after burn trauma may no longer be applicable, given the overall reduction in case-fatality rates after burn trauma. We expect that future advances in burn trauma research will require careful and ongoing quantification of mortality risk factors to measure the importance of newly identified factors and to determine the impact of new therapies. Conflicting clinical reports regarding the impact of gender on survival after sepsis and critical illness may in part, be from different study designs, patient samples, or failure to adequately control for additional factors contributing to the development ofsepsis and mortality. STUDY DESIGN: Data from the prospectively maintained burn registry for patients admitted to the Parkland Memorial Hospital burn unit between January 1, 1989 and December 31, 1998 were analyzed. Logistic regression was used to generate estimates of the probability of death in half of the study sample, and this model was validated on the second half of the sample. Risk factors evaluated for their relationship with mortality were: age, inhalation injury, burn size, body mass (weight), preexisting medical conditions, nonburn injuries, and gender. RESULTS: Of 4,927 patients, 5.3% died. The best model for estimating mortality included the percent of total body surface area burned; the percent of full-thickness burn size; the presence of an inhalation injury; age categories of: < 30 years, 30 to 59 years, > or = 60 years; and gender. The risk of death was approximately two fold higher in women aged 30 to 59 years compared with men of the same age. CONCLUSIONS: We have provided a detailed method for estimating the risk of mortality after burn trauma, based on a large, contemporary cohort of patients. These estimates were validated on a second sample and proved to predict mortality accurately. We have identified an increased mortality risk in women of 30 to 59 years of age. PMID- 11220715 TI - A potentially expanded role for enoxaparin in preventing venous thromboembolism in high risk blunt trauma patients. AB - BACKGROUND: Venous thromboembolism (VTE) is a frequent and potentially life threatening complication after trauma. The purpose of this study is to investigate the effectiveness of enoxaparin in preventing deep venous thrombosis (DVT) and pulmonary embolism (PE) after injury in patients who are at high risk for developing VTE. STUDY DESIGN: A prospective single-cohort observational study was initiated for seriously injured blunt trauma patients admitted to a Level I trauma center during a 7-month period. Patients were eligible for the study if time hospitalized was > or = 72 hours, Injury Severity Score (ISS) was > or = 9, enoxaparin was started within 24 hours after admission, and one or more of the following high risk criteria were met: age > 50 years, ISS > or = 16, presence of a femoral vein catheter, Abbreviated Injury Score (AIS) > or = 3 for any body region, Glasgow Coma Scale (GCS) Score < or = 8, presence of major pelvic, femur, or tibia fracture, and presence of direct blunt mechanism venous injury. Patients with closed head injuries and nonoperatively treated solid abdominal organ injuries were also potential participants. The primary outcomes measured were thromboembolic events--either a documented lower extremity DVT by duplex color flow doppler ultrasonography or a PE documented by rapid infusion CT pulmonary angiography or conventional pulmonary angiography. RESULTS: There were 118 patients enrolled in the study. Two patients (2%) developed DVT, one of which was proximal to the calf (95% confidence interval, 0% to 6%). Two of 12 patients (17%) with splenic injuries who received enoxaparin failed initial nonoperative management. There were no other bleeding complications, and no clinical evidence or documented episodes of PE. One patient died from multiple system organ failure. CONCLUSIONS: Enoxaparin is a practical and effective method for reducing the incidence of VTE in high risk, seriously injured patients. This study supports further investigation into the safety of enoxaparin prophylaxis in patients with closed head injuries and nonoperatively treated solid abdominal organ injuries. PMID- 11220716 TI - Safety and accuracy of bedside carbon dioxide cavography for insertion of inferior vena cava filters in the intensive care unit. AB - BACKGROUND: Bedside insertion of inferior vena caval filters (IVCFs) avoids risks associated with transporting these critically ill patients to the operating room or to the radiology suite. But because IVCF insertion requires preinsertion caval imaging, the risk of contrast-induced renal failure remains a concern. Carbon dioxide (CO2) as a contrast agent does not cause renal failure, but its accuracy in determining vena caval diameter (a critical factor in filter selection) and its safety in the critical care population are unknown. This study is designed to assess the safety of using CO2 as a contrast agent in this patient population and to evaluate its accuracy in determining the diameter of the inferior vena cava when used at the bedside. STUDY DESIGN: A prospective study comparing CO2 with iodinated contrast (IC) material was performed in critically ill patients undergoing vena cavography before bedside IVCF placement. CO2 cavagrams were performed with one or more hand injections of 60 mL of CO2; a single injection of 40 mL of IC material was used. Digital subtraction techniques were used for all of the studies. Blood pressure, pulse rate, and arterial oxygen saturation, end tidal CO2, and intracranial pressure (when available) were recorded before, during, and after contrast injection. Statistical analysis was performed using the paired t-test, with p < 0.05 being considered significant. Data are expressed as mean +/- SD. RESULTS: Twenty-three patients were studied. Mean transverse inferior vena cava (IVC) diameters measured 20.4 +/- 0.7mm (IC) and 20.0 +/- 0.7mm (CO2); p = 0.003. The difference in the measurements was 0.4 +/- 0.1 mm, with the largest difference being 1.7mm. In the remaining 10 patients, CO2 differed from IC in determining IVC diameter by only 0.4mm, a statistically significant (p < 0.05) but clinically insignificant difference. No adverse effects on blood pressure, pulse, arterial oxygen saturation, end-tidal CO2, or intracranial pressure were noted with the use of CO2. CONCLUSIONS: Carbon dioxide as a contrast agent is safe and provides accurate determination of vena caval diameter and anatomy. Carbon dioxide should be considered the contrast agent of choice in critically ill patients. PMID- 11220717 TI - Continued (5-year) followup of a randomized clinical study comparing antireflux surgery and omeprazole in gastroesophageal reflux disease. AB - BACKGROUND: The efficacy of antireflux surgery (ARS) and proton pump inhibitor therapy in the control of gastroesophageal reflux disease is well established. A direct comparison between these therapies is warranted to assess the benefits of respective therapies. STUDY DESIGN: There were 310 patients with erosive esophagitis enrolled in the trial. There were 155 patients randomized to continuous omeprazole therapy and 155 to open antireflux surgery, of whom 144 later had an operation. Because of various withdrawals during the study course, 122 patients originally having an antireflux operation completed the 5-year followup; the corresponding figure in the omeprazole group was 133. Symptoms, endoscopy, and quality-of-life questionnaires were used to document clinical outcomes. Treatment failure was defined to occur if at least one of the following criteria were fulfilled: Moderate or severe heartburn or acid regurgitation during the last 7 days before the respective visit; Esophagitis of at least grade 2; Moderate or severe dysphagia or odynophagia symptoms reported in combination with mild heartburn or regurgitation; If randomized to surgery and subsequently required omeprazole for more than 8 weeks to control symptoms, or having a reoperation; If randomized to omeprazole and considered by the responsible physician to require antireflux surgery to control symptoms; If randomized to omeprazole and the patient, for any reason, preferred antireflux surgery during the course of the study. Treatment failure was the primary outcomes variable. RESULTS: When the time to treatment failure was analyzed by use of the intention to treat approach, applying the life table analysis technique, a highly significant difference between the two strategies was revealed (p < 0.001), with more treatment failures in patients who originally were randomized to omeprazole treatment. The protocol also allowed dose adjustment in patients allocated to omeprazole therapy to either 40 or 60 mg daily in case of symptom recurrence. The curves subsequently describing the failure rates still remained separated in favor of surgery, although the difference did not reach statistical significance (p = 0.088). Quality of life assessment revealed values within normal ranges in both therapy arms during the 5 years. CONCLUSIONS: In this randomized multicenter trial with a 5-year followup, we found antireflux surgery to be more effective than omeprazole in controlling gastroesophageal reflux disease as measured by the treatment failure rates. But if the dose of omeprazole was adjusted in case of relapse, the two therapeutic strategies reached levels of efficacy that were not statistically different. PMID- 11220718 TI - Incidental appendectomy in the era of managed care and laparoscopy. AB - BACKGROUND: In a study carried out before laparoscopy or managed care, there was no cost or patient benefit for routine incidental appendectomy. With the onset oflaparoscopy, a change in indications for surgery, and increased prevalence of capitated contracts, a reanalysis of the cost-effectiveness of incidental appendectomy is warranted. STUDY DESIGN: Financial data from 251 patients undergoing appendectomy for acute appendicitis without complication at a single institution were identified. Age-specific epidemiology data from the Centers for Disease Control, Atlanta, were applied to assess risk and cost of future appendectomy. The net cost or savings for incidental appendectomies necessary to prevent one case of acute appendectomy was determined and stratified by gender and age to the population as a whole. Further adjustment was made for the variable level of surgeon reimbursement for incidental appendectomy. RESULTS: At 10% surgeon reimbursement, open incidental appendectomy was cost-effective in those less than 25 years of age (< 35 years of age in a capitated system). Applied to the general population, open incidental appendectomy in those less than 25 years represented savings of up to $1,100 per 10,000 population per year. A surgeon fee of greater than 50%, or the laparoscopic approach using staplers, accrued no savings in any age groups. CONCLUSIONS: Open incidental appendectomy at low physician reimbursement is a cost-effective procedure for patients of less than 35 years of age. A decrease in equipment cost for laparoscopic approach will extend these indications. PMID- 11220719 TI - Laparoscopic cholecystectomy does not demonstrably decrease survival of patients with serendipitously treated gallbladder cancer. AB - BACKGROUND: The purpose of this study was to evaluate the possibility that laparoscopic cholecystectomy has worsened the prognosis of patients with resected gallbladder cancer; particularly for patients whose cancer was accidentally resected. STUDY DESIGN: We conducted a retrospective review of Connecticut Tumor Registry data and data extracted from individual patient records at 15 of 30 hospitals in Connecticut reporting data to the Registry, at two separate time points, 1985-1988 (immediate prelaparoscopic era) and 1992-95 (laparoscopic cholecystectomy well established). There were 194 and 208 patients in each 3-year period, respectively. Additional information was extracted from hospital records in 82 and 91 patients, respectively. Twenty-five percent of patients in both data sets presented with "local" or Tis, T1, T2 disease. RESULTS: Three-year survival for localized disease was 29% in the prelaparoscopic period and 34% once laparoscopic cholecystectomy was established. But analysis of individual patient records indicated that 36% of patients from the laparoscopic period did not actually undergo a laparoscopic procedure. Fifty-nine patients had their gallbladder cancer discovered in the specimen postoperatively (serendipitously treated). A higher proportion of cancers were discovered postoperatively in the laparoscopic era (44% versus 24%). Three-year survival for these patients was 25%. If the data from the two eras are grouped according to whether or not the cancer-bearing gallbladder was manipulated laparoscopically, 24 of 59 patients (41%) turned out to be at risk for the possibility of increased laparoscopic dissemination of tumor. Survival of these patients (11-month median survival) was not statistically different from survival of patients whose serendipitously discovered gallbladder cancer was never manipulated laparoscopically (16-month median survival); p = 0.54 by log rank test. CONCLUSIONS: The widespread adoption of laparoscopic cholecystectomy did not worsen the survival of patients with gallbladder cancer, and patients with serendipitously treated gallbladder cancers did not have a worse survival after laparoscopic manipulation than after a standard open cholecystectomy. The laparoscopic aspects of operative manipulation of a gallbladder with cancer in it do not appear to be a proximate cause of the poor prognosis in this disease. PMID- 11220720 TI - Ductal carcinoma in situ (DCIS) of the breast: diagnostic and therapeutic controversies. PMID- 11220721 TI - Benjamin Church: physician, patriot, and spy. PMID- 11220722 TI - Systemic treatment after sentinel lymph node biopsy in breast cancer: who, what, and why? AB - SLNB, although subject to numerous technical problems, has nonetheless shown great promise in predicting the status of the remaining axillary lymph nodes. The growing use of SLNB has presented the opportunity of using immunohistochemical and molecular markers to detect occult micrometastases. These micrometastases may be important for more accurate staging and prediction of patient outcomes. Current standards for the use of systemic therapy recommend multidrug chemotherapy for all but the most favorable disease (T1a/b, NO). The detection of micrometastases by SLNB in this low-risk group may change treatment recommendations to include systemic therapy. Because of the significant frequency of false-negative results in SLNB, which will depend upon the surgeon's experience, caution is urged in determining when ALND can be safely eliminated in patients with a negative SLNB. PMID- 11220723 TI - Fullterm abdominal pregnancy, mother and infant survival. PMID- 11220724 TI - Boerhaave's syndrome. PMID- 11220725 TI - Transposition of the basilic vein for arteriovenous fistula: an endoscopic approach. PMID- 11220726 TI - Domino liver transplantation with end-to-side infrahepatic vena cavocavostomy. PMID- 11220727 TI - What's new in burns and metabolism. PMID- 11220728 TI - What's new in vascular surgery. PMID- 11220730 TI - NIH consensus panel recommends a range of adjuvant therapies for women with breast cancer. PMID- 11220729 TI - What's new in trauma and critical care. PMID- 11220731 TI - Yet another paraneoplastic antibody. PMID- 11220732 TI - Deep brain stimulation for Parkinson's disease. PMID- 11220733 TI - The case of the missing tau, or, why didn't the mRNA bark? PMID- 11220734 TI - CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. AB - We have defined a new paraneoplastic immunoglobulin G (IgG) autoantibody specific for CRMP-5, a previously unknown 62-kd neuronal cytoplasmic protein of the collapsin response-mediator family. CRMP-5 is in adult central and peripheral neurons, including synapses, and in small-cell lung carcinomas. Since 1993, our Clinical Neuroimmunology Laboratory has detected CRMP-5-IgG in 121 patients among approximately 68,000 whose sera were submitted for standardized immunofluorescence screening because a subacute neurological presentation was suspected to be paraneoplastic. This makes CRMP-5 autoantibody as frequent as PCA 1 (anti-Yo) autoantibody, second only to ANNA-1 (anti-Hu). Clinical information, obtained for 116 patients, revealed multifocal neurological signs. Most remarkable were the high frequencies of chorea (11%) and cranial neuropathy (17%, including 10% loss of olfaction/taste, 7% optic neuropathy). Other common signs were peripheral neuropathy (47%), autonomic neuropathy (31%), cerebellar ataxia (26%), subacute dementia (25%), and neuromuscular junction disorders (12%). Spinal fluid was inflammatory in 86%, and CRMP-5-IgG in 37% equaled or significantly exceeded serum titers. Lung carcinoma (mostly limited small-cell) was found in 77% of patients; thymoma was in 6%. Half of those remaining had miscellaneous neoplasms; all but two were smokers. Serum IgG in all cases bound to recombinant CRMP-5 (predominantly N-terminal epitopes), but not to human CRMP 2 or CRMP-3. PMID- 11220735 TI - Functional correlates of pallidal stimulation for Parkinson's disease. AB - We measured regional cerebral blood flow with H2 15O and positron emission tomography (PET) scanning at rest and during a motor task to study the mechanism of motor improvement induced by deep brain stimulation of the internal globus pallidus in Parkinson's disease. Six right-handed patients with Parkinson's disease were scanned while performing a predictable paced sequence of reaching movements and while observing the same screen displays and tones. PET studies were performed ON and OFF stimulation in a medication-free state. Internal globus pallidus deep brain stimulation improved off-state United Parkinson's Disease Rating Scale motor ratings (37%, p < 0.002) and reduced timing errors (movement onset time, 55%, p < 0.01) as well as spatial errors (10%, p < 0.02). Concurrent regional cerebral blood flow recordings revealed a significant enhancement of motor activation responses in the left sensorimotor cortex (Brodmann area [BA] 4), bilaterally in the supplementary motor area (BA 6), and in the right anterior cingulate cortex (BA 24/32). Significant correlations were evident between the improvement in motor performance and the regional cerebral blood flow changes mediated by stimulation. With internal globus pallidus deep brain stimulation, improved movement initiation correlated with regional cerebral blood flow increases in the left sensorimotor cortex and ventrolateral thalamus and in the contralateral cerebellum. By contrast, improved spatial accuracy correlated with regional cerebral blood flow increases in both cerebellar hemispheres and in the left sensorimotor cortex. These results suggest that internal globus pallidus deep brain stimulation may selectively improve different aspects of motor performance. Multiple, overlapping neural pathways may be modulated by this intervention. PMID- 11220736 TI - Loss of brain tau defines novel sporadic and familial tauopathies with frontotemporal dementia. AB - Dementia lacking distinctive histopathology (DLDH) or frontotemporal lobe degeneration (FTLD) is the most common neuropathological diagnosis for sporadic frontotemporal dementias (FTDs). The hallmarks of DLDH are neuron loss and gliosis in the absence of any disease-specific brain lesion. Similar brain pathology is also seen in a familial FTD pedigree known as hereditary dysphasic disinhibition dementia 2 (HDDD2). Abnormality in the function or isoform composition of the microtubule binding protein tau is a prominent feature in the brains of many patients with sporadic and hereditary FTDs. Therefore, we studied the tau protein in different brain regions from DLDH and HDDD2 patients. Our results indicate that a selective loss of all six tau isoforms, but not tau mRNA, occurs in these brains compared to normal control and Alzheimer's disease brains. Loss of tau protein was identified by Western blot analysis of protein extracts from DLDH and HDDD2 brains in regions both with and without neuronal degeneration. Functionally, this loss of tau protein may be equivalent to pathogenic mutations in the tau gene identified in familial FTD with parkinsonism linked to chromosome 17 (FTDP-17). Thus, DLDH and HDDD2 are novel tauopathies with a unique mechanism of pathogenesis. The presence of tau mRNA in these brains suggests that the level of tau protein may be controlled posttranscriptionally, at the level of either translation or mRNA stability. PMID- 11220737 TI - Increased expression of the pro-inflammatory enzyme cyclooxygenase-2 in amyotrophic lateral sclerosis. AB - Mutations in the copper/zinc superoxide dismutase (mSOD1) gene are associated with a familial form of amyotrophic lateral sclerosis (ALS), and their expression in transgenic mice produces an ALS-like syndrome. Recent observations suggest a role for inflammatory-related events in the progression and propagation of the neurodegenerative process in ALS. Consistent with this view, the present study demonstrates that, during the course of the disease, the expression of cyclooxygenase type 2 (Cox-2), a key enzyme in the synthesis of prostanoids, which are potent mediators of inflammation, is dramatically increased. In both early symptomatic and end-stage transgenic mSOD1 mice, neurons and, to a lesser extent, glial cells in the anterior horn of the spinal cord exhibit robust Cox-2 immunoreactivity. Cox-2 mRNA and protein levels and catalytic activity are also significantly increased in the spinal cord of the transgenic mSOD1 mice. The time course of the spinal cord Cox-2 upregulation parallels that of motor neuronal loss in transgenic mSOD1 mice. We also show that Cox-2 activity is dramatically increased in postmortem spinal cord samples from sporadic ALS patients. We speculate that Cox-2 upregulation, through its pivotal role in inflammation, is instrumental in the ALS neurodegenerative process and that Cox-2 inhibition may be a valuable therapeutic avenue for the treatment of ALS. PMID- 11220738 TI - Evolution of phenotypes in adult male patients with X-linked adrenoleukodystrophy. AB - Our objective was to study the phenotype evolution of X-linked adrenoleukodystrophy (X-ALD) and the relation between axonal degeneration and cerebral demyelination. Although different X-ALD phenotypes are recognized, little is known about their evolution. Neuropathological and electrophysiological studies have shown that X-ALD is a disease with mixed features of axonal degeneration, leading to myeloneuropathy, and a severe inflammatory reaction in the cerebral white matter, resulting in demyelination. Retrospectively, 129 men with X-ALD were studied who were 1) at least 20 years presently or at the time of death, and 2) regularly monitored. Phenotype assignments were made at diagnosis and at present, or at death, using medical history and findings of neurological examination. Handicap was studied with the modified Rankin scale, and cerebral abnormalities with the X-ALD MRI severity (Loes) score. The mean follow-up interval was 10.1 +/- 5.0 years. Among 32 patients neurologically asymptomatic at diagnosis, 16 (50%) developed neurological deficits. Among 68 adrenomyeloneuropathy (AMN) patients initially without clinical brain involvement, 13 (19%) additionally developed cerebral demyelination. In a subset of 60 AMN patients, a moderate handicap evolved over a period of 16.2 +/- 8.9 years. Among 13 AMN patients with additional definite or probable cerebral involvement at diagnosis, eight died and one remained in a vegetative state. Most of the 16 patients with the cerebral phenotypes deteriorated. There is a high risk for adult neurologically asymptomatic patients to develop neurological deficits and for AMN patients to develop cerebral demyelination. Axonal degeneration and cerebral demyelination emerge in X-ALD independently of each other. This may have implications for the phenotype classification, the search for modifying factors, and the development and evaluation of new therapies. PMID- 11220739 TI - Mutations in the complex I NDUFS2 gene of patients with cardiomyopathy and encephalomyopathy. AB - Human complex I is built up and regulated by genes encoded by the mitochondrial DNA (mtDNA) as well as the nuclear DNA (nDNA). In recent years, attention mainly focused on the relation between complex I deficiency and mtDNA mutations. However, a high percentage of consanguinity and an autosomal-recessive mode of inheritance observed within our patient group as well as the absence of common mtDNA mutations make a nuclear genetic cause likely. The NDUFS2 protein is part of complex I of many pro- and eukaryotes. The nuclear gene coding for this protein is therefore an important candidate for mutational detection studies in enzymatic complex I deficient patients. Screening of patient NDUFS2 cDNA by reverse transcriptase-polymerase chain reaction (RT-PCR) in combination with direct DNA sequencing revealed three missense mutations resulting in the substitution of conserved amino acids in three families. PMID- 11220740 TI - Loss and atrophy of layer II entorhinal cortex neurons in elderly people with mild cognitive impairment. AB - Layer II of the entorhinal cortex contains the cells of origin for the perforant path, plays a critical role in memory processing, and consistently degenerates in end-stage Alzheimer's disease. The extent to which neuron loss in layer II of entorhinal cortex is related to mild cognitive impairment without dementia has not been extensively investigated. We analyzed 29 participants who came to autopsy from our ongoing longitudinal study of aging and dementia composed of religious clergy (Religious Orders Study). All individuals underwent detailed clinical evaluation within 12 months of death and were categorized as having no cognitive impairment (n = 8), mild cognitive impairment (n = 10), or mild or moderate Alzheimer's disease (n = 11). Sections through the entorhinal cortex were immunoreacted with an antibody directed against a neuron-specific nuclear protein (NeuN). Stereological counts of NeuN-immunoreactive stellate cells, their volume, and the volume of layer II entorhinal cortex were estimated. Cases exhibiting no cognitive impairment averaged 639,625 +/- 184,600 layer II stellate neurons in the right entorhinal cortex. Individuals with mild cognitive impairment (63.5%; p < 0.0003) and mild or moderate Alzheimer's disease (46.06%; p < 0.0017) displayed significant losses of layer II entorhinal cortex neurons relative to those with no cognitive impairment but not relative to each other (p > 0.33). There was also significant atrophy of layer II entorhinal cortex neurons in individuals with mild cognitive impairment (24.1%) and Alzheimer's disease (25.1%). The volume of layer II was also reduced in individuals with mild cognitive impairment (26.5%), with a further reduction in those with Alzheimer's disease (46.4%). The loss and atrophy of layer II entorhinal cortex neurons significantly correlated with performance on clinical tests of declarative memory. Atrophy of layer II entorhinal cortex and the neurons within this layer significantly correlated with performance on the Mini Mental Status Examination. These data indicate that atrophy and loss of layer II entorhinal cortex neurons occur in elderly subjects with mild cognitive impairment prior to the onset of dementia and suggests that these changes are not exacerbated in early Alzheimer's disease. PMID- 11220741 TI - Paraneoplastic anti-CV2 antibodies react with peripheral nerve and are associated with a mixed axonal and demyelinating peripheral neuropathy. AB - Subacute sensory neuronopathy with anti-Hu antibodies is the best-characterized paraneoplastic peripheral neuropathy associated with carcinoma. Anti-CV2 antibodies, another group of paraneoplastic antibodies, react with a 66-kd brain protein belonging to the family of Ulip/CRMP proteins. The manifestations associated with anti-CV2 antibodies include cerebellar degeneration, uveitis, and peripheral neuropathy. Some of these patients also have anti-Hu antibodies. We have compared the clinical, electrophysiological, and pathological characteristics of the peripheral neuropathy in 9 patients with anti-CV2 antibodies (3 of whom also had anti-Hu antibodies) and 12 patients with only anti Hu antibodies. Data for patients with anti-Hu antibodies alone indicated subacute sensory neuronopathy. Patients with anti-CV2 antibodies had a mixed axonal and demyelinating sensory motor neuropathy that was sometimes superimposed on subacute sensory neuronopathy when both anti-CV2 and anti-Hu antibodies were present. Unlike anti-Hu antibodies, anti-CV2 antibodies reacted with peripheral nerve antigens, as shown by their ability to bind to a 66-kd protein in human and rat nerve on Western blot analysis and to immunolabel peripheral nerve axons and sensory neurons on immunohistochemical study. PMID- 11220742 TI - Improved cerebrovascular patency following therapy in patients with sickle cell disease: initial results in 4 patients who received HLA-identical hematopoietic stem cell allografts. AB - To test whether magnetic resonance angiography can document the evolution of vasculopathy in patients with sickle cell disease, we reviewed records to identify all patients who underwent magnetic resonance angiography from 1993 to 1999. Of 512 angiographies performed, 105 were of sickle cell disease patients, and 24 sickle cell disease patients 7 years of age or older underwent baseline and follow-up examinations. Films were paired by patient, blinded as to examination date and treatment, and quantitatively compared. Four patients who received allogeneic bone marrow transplantation were compared to 7 patients who received other therapy and to 13 untreated patients. Quantitative analysis revealed a 10% increase in the measured diameter of 64 vessels (p = 0.001) following any treatment. Patients who had undergone allogeneic bone marrow transplantation exhibited a 12% increase in the lumen of 22 vessels (p = 0.041), whereas patients treated with chronic transfusion or hydroxyurea exhibited an 8% increase in 42 vessels (p = 0.016). In 2 patients with severe stenosis, the artery normalized after transplantation, and the blood flow rate was reduced in all patients who underwent transplantation. In untreated patients, there was a trend for the size of the arterial lumen to decrease, which is consistent with disease progression. Results suggest that treatment can reverse progression of vasculopathy. Bone marrow transplantation may enable stenoses to heal and can substantially reduce cranial blood velocity, suggesting that allogeneic bone marrow transplantation may prevent infarction or brain damage. PMID- 11220743 TI - HIV-1 Tat neurotoxicity is prevented by matrix metalloproteinase inhibitors. AB - The release of potentially neurotoxic molecules by HIV-infected brain macrophages is accompanied by neuronal injury and death that results in the development of HIV-associated dementia (HAD). Among the potential neurotoxins implicated in the development of HAD is the HIV-1 transactivating protein, Tat. To investigate the mechanism by which Tat causes neurotoxicity, brain-derived Tat sequences from nondemented (Tat-ND) and demented (Tat-HAD) AIDS patients, which differed primarily in the augmenting region of Tat, were expressed in U937 monoblastoid cells and primary human macrophages. Cells expressing Tat-HAD protein exhibited elevated matrix metalloproteinase (MMP)-2 and -7 release and activation, but cells expressing Tat-ND did not exhibit enhanced MMP expression. Conditioned media from Tat-HAD-transfected cells caused significantly greater neuronal death (15.4 +/- 4.3%) than did Tat-ND (4.4 +/- 2.1%) or nontransfected (2.1 +/- 0.8%) cell-derived conditioned media. The neurotoxicity induced by Tat-HAD was inhibited by anti-MMP-2 or -7 antibodies (p < 0.005) but not by antibodies against MMP-9 or Tat. Similarly, scid/nod mice receiving striatal implants of Tat HAD-transfected cells exhibited greater neurobehavioral abnormalities and neuronal loss (p < 0.005) than did animals receiving Tat-ND or nontransfected cells, which were reduced by treatment with the MMP inhibitor prinomastat (p < 0.005). These findings indicate that Tat causes neuronal death through an indirect mechanism that is Tat sequence dependent and involves the induction of MMPs. PMID- 11220744 TI - Abnormal activity in the globus pallidus in off-period dystonia. AB - Pallidotomy was performed in a parkinsonian patient with off-period foot dystonia. Dystonia appeared at the beginning of surgery and disappeared after the first microelectrode penetration of the globus pallidus, perhaps a micropallidotomy effect. Neuronal recording during dystonia revealed that the mean firing rates were low in both the internal and external segments of the globus pallidus, and that firing was irregular in the internal segment of the globus pallidus, compared with firing patterns in offstate parkinsonian patients without dystonia. These firing patterns immediately changed into those of nondystonic, off-state parkinsonism after relief of dystonia These results suggest that off-period dystonia results from the same physiological change in the basal ganglia as that in primary dystonia. PMID- 11220745 TI - Further evidence that neurofilament light chain gene mutations can cause Charcot Marie-Tooth disease type 2E. AB - A missense mutation in the neurofilament light chain gene (NEFL, NF-L) at chromosome 8p21 was recently reported in a single Charcot-Marie-Tooth type 2 family (CMT2). This new CMT2 variant is designated CMT2E. The NEFL gene mutation showed co-segregation with the disease phenotype and is thus most likely the disease-causing mutation. However, the possibility that it is a closely linked rare polymorphism can not be ruled out with certainty. We observed a novel NEFL missense mutation in a second CMT family, providing supporting evidence that CMT2E is caused by NEFL gene mutations. PMID- 11220746 TI - Anti-Yo antibodies and cerebellar degeneration in a man with adenocarcinoma of the esophagus. AB - Serum antibodies to the Yo antigen are usually associated with paraneoplastic cerebellar degeneration arising in female patients with gynecological or breast malignancy and are rarely associated with other tumors. We report a male patient who presented with paraneoplastic cerebellar degeneration and anti-Yo antibodies following removal of an esophageal adenocarcinoma. This is only the third report of anti-Yo antibodies occurring in a male patient. The Yo antigen was expressed by the esophageal tumor but not in a frontal lobe cerebral metastasis identified at postmortem. Interestingly, CD8+ T-cell infiltration was also found in the tumor, but not in the metastasis, consistent with down-regulation of Yo expression by the tumor cells leading to evasion from immune-mediated tumor surveillance. PMID- 11220747 TI - 14-3-3 protein cerebrospinal fluid detection in human growth hormone-treated Creutzfeldt-Jakob disease patients. AB - The usefulness of the detection of 14-3-3 protein in the cerebrospinal fluid (CSF) in the diagnosis of Creutzfeldt-Jakob disease transmitted from human growth hormone was evaluated in 20 French patients. The 14-3-3 protein was rarely detectable within the first 3 months of the disease but always positive after 7 months associated with the aggravation of the disease and the occurrence of dementia. 14-3-3 detection was not predictive of the survival time of the patients. The genotype at PRNP codon 129 could influence the timing of appearance of the 14-3-3 protein in the CSF. PMID- 11220748 TI - Propofol in subanesthetic doses terminates status epilepticus in a rodent model. AB - Status epilepticus is commonly refractory to first-line therapy, and thus better treatments are needed. We have investigated an experimental model of drug resistant self-sustaining status epilepticus (SSSE) induced by 2 hours of perforant path stimulation. Propofol in subanesthetic doses administered shortly after the end of stimulation and also after a further 3 hours of SSSE terminated the SSSE without recurrence. This finding calls for a trial of propofol in refractory status epilepticus and also raises the possibility of using it as first-line therapy. PMID- 11220749 TI - Familial atypical progressive supranuclear palsy associated with homozigosity for the delN296 mutation in the tau gene. AB - Heterozygous missense and splice-site mutations in the tau gene have been previously identified in familial frontotemporal dementia with autosomal dominant inheritance. Here we report a Spanish kindred in which two brothers born from a third-degree consanguineous marriage were both affected with atypical progressive supranuclear palsy. A homozygous deletion at codon 296 (delN296) was identified in one of the affected siblings. Among the heterozygous carriers, two members with probable Parkinson's disease were identified, but none of heterozygotes developed atypical parkinsonism. The delN296 mutation lies in the sequence corresponding to the second tubulin-binding repeat of tau protein and affects one asparagine residue absolutely conserved in other species. This finding indicates that homozygous mutations in the tau gene may also cause hereditary tauopathies. PMID- 11220750 TI - Compound heterozygous D90A and D96N SOD1 mutations in a recessive amyotrophic lateral sclerosis family. AB - We describe a French amyotrophic lateral sclerosis (ALS) family with two distinct mutations in the Cu/Zn superoxide dismutase (SOD1) gene. The D90A mutation has been well described and clearly shown to cause recessive ALS. In this family, affected individuals are heterozygous for the D90A mutation and also carry a single copy of a novel SOD1 mutation, D96N. We propose that in this family both mutations are required for the development of disease. PMID- 11220751 TI - Laforin is a cell membrane and endoplasmic reticulum-associated protein tyrosine phosphatase. AB - Lafora disease (LD) is the only progressive myoclonus epilepsy with polyglucosan bodies. Among conditions with polyglucosan bodies, LD is unique for the subcellular location of its polyglucosans in neuronal perikarya and dendrites and not in axons. Here we report that the protein encoded by the EPM2A gene, which is mutated in LD, localizes at the plasma membrane and the endoplasmic reticulum and that it is a functional protein tyrosine phosphatase. The significance of these findings in the epilepsy of LD and in the origin and characteristic subcellular location of Lafora bodies is discussed. PMID- 11220752 TI - Role for peroxisome proliferator-activated receptor-gamma in Alzheimer's disease. PMID- 11220753 TI - No evidence of association between a dopamine transporter gene polymorphism (1215A/G) and Parkinson's disease. PMID- 11220754 TI - Care should be taken in interpretation of visual field tests in children. PMID- 11220755 TI - Therapeutic efficacy of a combination of artemether and lumefantrine (co artemether) versus chloroquine in treatment of uncomplicated cases of Plasmodium falciparum malaria. PMID- 11220756 TI - Virus-expressed, recombinant single-chain antibody blocks sporozoite infection of salivary glands in Plasmodium gallinaceum-infected Aedes aegypti. AB - Transgenic mosquitoes resistant to malaria parasites are being developed to test the hypothesis that they may be used to control disease transmission. We have developed an effector portion of an antiparasite gene that can be used to test malaria resistance in transgenic mosquitoes. Mouse monoclonal antibodies that recognize the circumsporozoite protein of Plasmodium gallinaceum can block sporozoite invasion of Aedes aegypti salivary glands. An anti-circumsporozoite monoclonal antibody, N2H6D5, whose corresponding heavy- and light-chain gene variable regions were engineered as a single-chain antibody construct, binds to P. gallinaceum sporozoites and prevents infection of Ae. aegypti salivary glands when expressed from a Sindbis virus. Mean intensities of sporozoite infections of salivary glands in mosquitoes expressing N2scFv were reduced as much as 99.9% when compared to controls. PMID- 11220757 TI - PCR-RFLP analysis of the ITS2 region to identify Schistosoma haematobium and S. bovis from Kenya. AB - Schistosoma haematobium, primarily a human parasite, and the closely related Schistosoma bovis from ruminants, are sympatric in many African countries such as Kenya. Because these two species 1) can inhabit the same Bulinus snails, 2) may be found in the same freshwater habitat, and 3) have morphologically similar cercariae, better means are needed to tell them apart. The second internal transcribed spacer (ITS2) region of the ribosomal gene complex (rDNA) of recent Kenyan isolates of both species was sequenced and found to be a 98% match. The S. bovis sequences were nearly identical (99%) to conspecific sequences from Niger; the S. haematobium sequences were nearly identical (99%) to conspecific sequences from Egypt, Mali, and Niger. Restriction fragment length polymorphism (RFLP) analysis of a 480 base pair (bp) PCR product containing the ITS2 region using two restriction enzymes, Taq1 and Sau3A1, yielded species-specific fragment patterns that allowed successful identification of a single S. haematobium cercaria. The protocol outlined here is useful in providing a rapid, one-day identification of S. haematobium (and likely S. bovis) cercariae (the infective larval stage) and/or other life cycle stages in a basic molecular biology laboratory. By helping to determine whether schistosome-infected bulinid snails in a particular body of water are transmitting a human or an animal schistosome, or both, this analysis will aid in disease control and in ongoing epidemiological studies. PMID- 11220758 TI - Molecular typing of Trichomonas vaginalis isolates by HSP70 restriction fragment length polymorphism. AB - Subtyping isolates of Trichomonas vaginalis is an essential tool for understanding the epidemiology of this common sexually-transmitted disease. Restriction fragment length polymorphism (RFLP) analysis employing a probe from the heat-inducible cytoplasmic HSP70 gene family hybridized with EcoR I-digested genomic DNA was used in the molecular typing of Trichomonas isolates. Analysis of five American Type Culture Collection (ATCC) reference strains and 31 Jackson, Mississippi, isolates from six male and 21 female patients, revealed 10 distinct RFLP pattern subtypes of Trichomonas. The subtypes were temporally stable and cosmopolitan. The RFLP profiles seen in Maryland, Ohio, Massachusetts, and New York ATCC strains were identical to those of some Mississippi isolates, even though the samples were isolated 10-35 years apart. There was no correlation between metronidazole resistance and RFLP subtype with resistant isolates from eight patients distributed among six different subtypes. PMID- 11220759 TI - Genetic variation of Japanese encephalitis virus in Taiwan. AB - A 280-nucleotide sequence from the capsid-premembrane (C/preM) gene region of 44 Japanese encephalitis (JE) virus strains isolated in Taiwan from mosquitoes from 1983 to 1994, and 3 strains, (Ling [1965], Chang [1965], and HV1 [1958]) isolated from human brain were analyzed by direct sequencing of reverse transcription polymerase chain reaction (RT-PCR) amplified products and compared with the corresponding sequences of reference strains. The overall sequence homology of the 47 isolates was > or = 93.3%. Taking 12% nucleotide divergence as a cut-off value, all isolates fell into genotype 3, which included strains from Japan, China, the Philippines, Sri Lanka, India, and Nepal. High nucleotide homology was observed among isolates from different regions of Taiwan and different time periods; on the other hand, high variation existed among isolates from the same region and time period. Phylogenetic analysis showed that the 47 Taiwan isolates fell into three clusters. Twenty-five isolates formed cluster 1, 18 isolates cluster 2, and four isolates cluster 3. Isolates in cluster 1 showed greater (< or = 2.9%) intragroup divergence compared to those in cluster 2 (< or = 1.1%) or cluster 3 (< or = 0.7%). The majority of isolates from northern (73.3%) and central (60%) Taiwan belonged to cluster 1, whereas most isolates (66.7%) from southern Taiwan belonged to cluster 2. Comparison with other Asian JE virus strains showed that isolates of cluster 1 were more specific to Taiwan than isolates of cluster 2 and cluster 3. PMID- 11220760 TI - Erhaia (Gastropoda: Rissooidea): phylogenetic relationships and the question of Paragonimus coevolution in Asia. AB - The human lung fluke Paragonimus is transmitted by gastropod taxa of two superfamilies: Ceritheoidea and Rissooidea. The question whether or not Paragonimus shows the same specificity of host-parasite coevolved relationship as the human blood fluke Schistosoma was inspired by the finding of two sympatric snail species as hosts for Paragonimus skrjabini in Fujian Province, China: Gammatricula and Erhaia. The former species can clearly be classified as Pomatiopsidae: Triculinae. The latter has previously been classified as Pomatiopsidae: Pomatiopsinae. However, this classification based on anatomical characteristics is uncertain. In order to obtain a robust phylogenetic hypothesis for Erhaia, we have studied three gene fragments from this taxon as well as from twelve related taxa. The data show that the species involved represent four families: Pomatiopsidae, Hydrobiidae, Cochliopidae (here raised to family status), and Amnicolidae. Erhaia fits securely into the Amnicolidae. This indicates that P. skrjabini has not coevolved with snail lineages. However, P. skrjabini has so far only been reported from rissooidean snails, whereas members of the Paragonimus westermani complex have only been found in ceritheoidean snails. The implication is that there is a host specificity on the superfamily level. However, Asian freshwater species of the Ceritheoidea and Rissooidea usually are not sympatric and often prefer different habitats. It is therefore possible that ecological niche partitioning plays the primary role for Paragonimus evolution. PMID- 11220761 TI - Phylogeny and molecular taxonomy of the Rhodniini derived from mitochondrial and nuclear DNA sequences. AB - Eleven species of Rhodnius and one of Psammolestes were compared by DNA sequence analysis of fragments of the mitochondrial large subunit ribosomal RNA (mtlsurRNA), the mitochondrial cytochrome b (mtCytb), and the D2 variable region of the 28S nuclear RNA (D2), totaling 1,429 base pairs. The inferred phylogeny, using Triatoma infestans as an outgroup, revealed two main clades within the Rhodniini--one, including the prolixus group of species (Rhodnius prolixus, Rhodnius robustus, Rhodnius neglectus, and Rhodnius nasutus) together with Rhodnius domesticus and Rhodnius neivai, and the other comprising two groups formed by Rhodnius pictipes plus Rhodnius brethesi, and Rhodnius ecuadoriensis plus Rhodnius pallescens. Psammolestes tertius appeared most closely related to the prolixus group. The analysis strongly supports the validity of R. robustus as a species distinct from others of the prolixus group, but suggests higher genetic structuring of R. robustus populations compared to the other species. Although R. robustus has been found naturally infected by Trypanosoma cruzi, the fact that it is apparently entirely sylvatic and unable to establish in homes suggests that it is of no great importance as a Chagas disease vector in humans. PMID- 11220762 TI - Efficacy of vaccines containing rhoptry-associated proteins RAP1 and RAP2 of Plasmodium falciparum in Saimiri boliviensis monkeys. AB - A vaccine trial was conducted with rhoptry-associated proteins 1 and 2 (RAP1 and RAP2) of Plasmodium falciparum in Saimiri boliviensis monkeys to compare the ability of parasite-derived (PfRAP1 and 2) and recombinant proteins (rRAP1 and 2) to induce protective immune responses and to find adjuvants suitable for use in humans. Eight groups of 6 monkeys each were immunized with parasite-derived or recombinant RAP1 and 2 with Freund's complete adjuvant (FCA) followed by Freund's incomplete adjuvant (FIA), Montanide ISA720 adjuvant, or CRL1005 adjuvant. Recombinant RAP1 and RAP2 were also administered separately, with Montanide ISA720. After 3 immunizations, monkeys were challenged by iv inoculation of 50,000 parasites of the Uganda Palo Alto strain of P. falciparum. Of the animals vaccinated using FCA/FIA, 1 of 6 control monkeys, 3 of 6 immunized with PfRAP1 and 2, and 2 of 6 with rRAP1 and 2 did not require drug treatment. Of the monkeys vaccinated with Montanide ISA720 adjuvant, 0 of the 6 control monkeys, 2 of 6 immunized with RAP1 and 2, 1 of 6 immunized with rRAP1, and 4 of 6 immunized with RAP2 did not require drug treatment. Two of 6 monkeys immunized with PfRAP1 and 2 with CRL1005 did not require treatment. All groups receiving RAP1, RAP2, or both had a significant decrease in initial parasite multiplication rates and there was a significant negative correlation between anti-RAP2 antibody and multiplication rates. Animals were rechallenged with the homologous parasite 126 days after the first challenge. Of the monkeys that did not require drug treatment after the first challenge, none developed detectable parasitemia following rechallenge. PMID- 11220763 TI - Growth characteristics of the chimeric Japanese encephalitis virus vaccine candidate, ChimeriVax-JE (YF/JE SA14--14--2), in Culex tritaeniorhynchus, Aedes albopictus, and Aedes aegypti mosquitoes. AB - The Japanese encephalitis (JE) virus vaccine candidate, ChimeriVax-JE, which consists of a yellow fever (YF) 17D virus backbone containing the prM and E genes from the JE vaccine strain JE SA14--14--2, exhibits restricted replication in non human primates, producing only a low-level viremia following peripheral inoculation. Although this reduces the likelihood that hematophagous insects could become infected by feeding on a vaccinated host, it is prudent to investigate the replication kinetics of the vaccine virus in mosquito species that are known to vector the viruses from which the chimera is derived. In this study ChimeriVax-JE virus was compared to its parent viruses, as well as to wild type JE virus, for its ability to replicate in Culex tritaeniorhynchus, Aedes albopictus, and Aedes aegypti mosquitoes. Individual mosquitoes were exposed to the viruses by oral ingestion of a virus-laden blood meal or by intrathoracic (IT) virus inoculation. ChimeriVax-JE virus did not replicate following ingestion by any of the three mosquito species. Additionally, replication was not detected after IT inoculation of ChimeriVax-JE in the primary JE virus vector, Cx. tritaeniorhynchus. ChimeriVax-JE exhibited moderate growth following IT inoculation into Ae. aegypti and Ae. albopictus, reaching titers of 3.6-5.0 log(10) PFU/mosquito. There was no change in the virus genotype associated with replication in mosquitoes. Similar results were observed in mosquitoes of all three species that were IT inoculated or had orally ingested the YF 17D vaccine virus. In contrast, all mosquitoes either IT inoculated with or orally fed wild type and vaccine JE viruses became infected, reaching maximum titers of 5.4-7.3 log(10) PFU/mosquito. These results indicate that ChimeriVax-JE virus is restricted in its ability to infect and replicate in these mosquito vectors. The low viremia caused by ChimeriVax-JE in primates and poor infectivity for mosquitoes are safeguards against secondary spread of the vaccine virus. PMID- 11220764 TI - Randomized trial of the immunogenicity of fractional dose regimens of PRP-T Haemophilus influenzae type b conjugate vaccine. AB - To assess the immunogenicity of more economical regimens of Haemophilus influenzae type b (Hib) conjugate vaccine, a randomized trial of fractional doses of polyribosylribitol phosphate-tetanus toxoid (PRP-T) Hib vaccine was undertaken in the Dominican Republic. Six hundred children were assigned to one of six regimens with PRP-T vaccine: full-dose, half-dose, and one-third-dose of Hib vaccine given separately or combined with diphtheria, tetanus, and pertussis (DTP) vaccine at ages 2, 4, and 6 months. Regimens that elicited antibody levels > 1.0 microg/mL in >70% of children and < or = 0.15 microg/mL in > 90% of children were considered acceptable. At 1 month post Dose 3, all regimens met the criteria for acceptable response. Among those who received Hib as a separate injection, geometric mean concentrations of anti-PRP bodies (GMCs) at age 1 month post Dose 3 were 11.2, 11.9, and 16.3 in the full, half, and one-third dose groups, respectively. Among those who received Hib and DTP combined, the GMCs were 6.4, 5.2, and 5.7 in the full-, half-, and one-third-dose groups respectively. PMID- 11220765 TI - Adaptation of a chloroquine-resistant strain of Plasmodium vivax from Indonesia to New World monkeys. AB - The spread of chloroquine-resistant Plasmodium vivax from Papua New Guinea and Indonesia poses a serious health threat to areas of Southeast Asia where this species of malaria parasite is endemic. A strain of P. vivax from Indonesia was adapted to develop in splenectomized Aotus lemurinus griseimembra, Aotus vociferans, Aotus nancymai, and Saimiri boliviensis monkeys. Transmission to splenectomized Saimiri monkeys was obtained via sporozoites. Chemotherapeutic studies indicated that the strain was resistant to chloroquine and amodiaquine while sensitive to mefloquine. Infections of chloroquine-resistant P.vivax in New World monkeys should be useful for the development of alternative treatments. PMID- 11220766 TI - Economic hardship and sexually transmitted diseases in Haiti's rural Artibonite Valley. AB - A study was conducted to determine the prevalence rate and risk factors for sexually transmitted diseases (STDs) in Haiti's rural Artibonite Valley. Women attending antenatal services at Hospital Albert Schweitzer from October to December 1996 were tested for gonorrhea, chlamydia, trichomonas, syphilis, and human immunodeficiency virus (HIV). Of the 476 women tested, 121 (25.4%) had trichomonas, 11/475 (2.3%) had gonorrhea, 51/475 (10.7%) had chlamydia, 32/474 (6.8%) were seropositive for syphilis, 20/469 (4.3%) were seropositive for HIV, and 191 (40.1%) had at least one STD. Nearly 30% of the women reported having entered a sexual relationship out of economic necessity and had increased odds of HIV infection, Odds Ratio (OR) 6.3 (P < 0.001). We postulate that due to recent economic hardship in rural Haiti, women are entering into sexual relationships out of economic necessity and that this trend is contributing to the growing HIV epidemic. We recommend STD prevention and development programs that target young people and economically disadvantaged women. PMID- 11220767 TI - Evaluation of the whole blood filariasis ICT test for short-term monitoring after antifilarial treatment. AB - The immunochromatographic (ICT) filariasis test is a rapid screening tool that will be useful for defining the prevalence and distribution of Wuchereria bancrofti as part of the global program to eliminate lymphatic filariasis. To address questions about its usefulness for monitoring control programs, we used the ICT filariasis test to assess residual antigen levels following antifilarial treatment. Our results demonstrate that antigen levels persist in microfilaria negative persons for up to three years after treatment. Different strategies for monitoring control programs may have to be considered. PMID- 11220768 TI - Effect of Plasmodium falciparum parasitemia density on hemoglobin concentrations among full-term, normal birth weight children in western Kenya, IV. The Asembo Bay Cohort Project. AB - The relative importance of acute high-density versus persistent low-density Plasmodium falciparum parasitemia in contributing to the public health problem of malarial anemia remains unclear. The Asembo Bay Cohort Project in western Kenya collected monthly hemoglobin (Hb) and parasitologic measurements and biweekly assessments of antimalarial drug use among 942 singleton live births between 1992 and 1996. A mixed-model analysis appropriate for repeated measures data was used to study how time-varying parasitemia and antimalarial drug exposures influenced mean Hb profiles. Incidence of World Health Organization-defined severe malarial anemia was 28.1 per 1,000 person-years. Among children aged less than 24 months, concurrent parasitemia was significantly associated with lower mean Hb, especially when compared to children with no concurrent parasitemia. Increased densities of the 90-day history of parasitemia preceding Hb measurement was more strongly associated with mean Hb levels than concurrent parasitemia density. While the highest quartile of 90-day parasitemia history was associated with lowest mean Hb levels, children in the lowest 90-day exposure quartile still experienced significantly lower Hb levels when compared to children who remained parasitemia-free for the same 90-day period. The results highlight the importance of collecting and analyzing longitudinal Hb and parasitologic data when studying the natural history of malarial anemia. PMID- 11220769 TI - New insights on the emergence of cholera in Latin America during 1991: the Peruvian experience. AB - After a century of absence, in late January 1991, Vibrio cholerae invaded the Western Hemisphere by way of Peru. Although a number of theories have been proposed, it is still not understood how that invasion took place. We reviewed the clinical records of persons attending hospital emergency departments in the major coastal cities of Peru from September through January of 1989/1990 and 1990/1991. We identified seven adults suffering from severe, watery diarrhea compatible with a clinical diagnosis of cholera during the four months preceding the cholera outbreak, but none during the previous year. The patients were scattered among five coastal cities along a 1,000 km coastline. We postulate that cholera vibrios, autochthonous to the aquatic environment, were present in multiple coastal locations, and resulted from environmental conditions that existed during an El Nino phenomenon. Once introduced into the coastal communities in concentrations large enough for human infection to occur, cholera spread by the well-known means of contaminated water and food. PMID- 11220770 TI - Detection of Fasciola hepatica infection in a community located in the Ecuadorian Andes. AB - The presence of fascioliasis was assessed in four Andean communities using an enzyme-linked immunosorbent assay (ELISA) test to measure antibodies against Fasciola hepatica excretion-secretion antigens. Six percent (9 out of 150) of the individuals in one community were ELISA-positive for these antibodies. Fecal samples from two of the ELISA-positive individuals contained F. hepatica ova. All of the ELISA-positive cases, except for one, were children within the ages of 9 to 12 years. PMID- 11220771 TI - Prevalence of antibodies to hepatitis E in two rural Egyptian communities. AB - A population-based serosurvey in two rural Egyptian communities was used to assess age-specific prevalence of antibody to hepatitis E virus (anti-HEV). One community is in the Nile Delta (11,182 inhabitants; 3,997 participants) and the other in Upper Egypt (10,970 inhabitants; 6,029 participants). Samples were tested for anti-HEV with a commercial enzyme-linked immunoassay (ELISA) based on antigens derived from open reading frame (ORF)2 and ORF3. Although there was a clear difference in sensitivity among the lots of the commercial test used, it was still possible to determine the seroprevalence. The seroprevalence of anti HEV exceeded 60% in the first decade of life, peaked at 76% in the second decade and remained above 60% until the eighth decade. Prevalence of this magnitude is among the highest reported in the world, with an age-specific pattern more similar to hyperendemic hepatitis A virus transmission than generally described. Lot-to-lot variation in the sensitivity of the commercial ELISA kit highlights a problem when comparing seroepidemiologic studies of different populations. PMID- 11220772 TI - A randomized controlled trial of artemotil (beta-arteether) in Zambian children with cerebral malaria. AB - The efficacy and safety of intramuscular artemotil (ARTECEF) was compared to intravenous quinine in African children with cerebral malaria. This prospective block randomized open-label study was conducted at two centers in Zambia. Subjects were children aged 0 to 10 years of age with cerebral malaria and a Blantyre Coma Score of 2 or less. Ninety two children were studied; 48 received artemotil and 44 quinine. No significant differences in survival, coma resolution time, neurologic sequelae, parasite clearance time, and fever resolution time were seen between the two regimens. Rates for negative malaria smears one month after therapy were similar in both groups. Artemotil was a well-tolerated drug in the 48 patients in this study. It appears to be at least therapeutically equivalent to quinine for the treatment of pediatric cerebral malaria. It has the advantage of being able to be given intramuscularly once daily for only five days. PMID- 11220773 TI - Expression of proinflammatory cytokines in four regions of the brain in Macaque mulatta (rhesus) monkeys infected with Plasmodium coatneyi. AB - We have characterized brain cytokine expression profiles in the Plasmodium coatneyi/rhesus (Macaque mulatta) malaria model. Eight rhesus monkeys were included in the study; four were infected with P. coatneyi, and four were used as uninfected controls. All inoculated animals became infected. Eleven days after parasite inoculation, the rhesus monkeys were killed and tissue samples from 4 regions of the brain (cortex and white matter of the cerebrum, cerebellum, and midbrain) were collected for quantitation of mRNA expression of cytokines, adhesion molecules, and inducible nitric oxide synthetase (iNOS) by reverse transcriptase-polymerase chain reaction (RT-PCR). The expression levels of tumor necrosis actor-alpha (TNF-alpha), gamma interferon (IFN-gamma), interleukin-1 beta (IL-1beta), intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synethetase (iNOS) were highest in the cerebellum of infected animals, correlating well with pathologic observations of sequestration of parasitized erythrocytes in this region of the brain. Infected animals also had higher TNF alpha expression levels in the cortex and IL-1beta expression levels in the cortex, white matter, and midbrain. Thus, the expression of pro-inflammatory and T helper-1 (TH-1) cytokines, adhesion molecules, and iNOS appears to predominate in the cerebellum of infected rhesus monkeys. PMID- 11220774 TI - 5HT7 receptors in the rodent suprachiasmatic nucleus. AB - Serotonergic modulation of circadian rhythms in rodent model preparations has received considerable attention over the past decade. Investigators have also been trying to determine which of the many serotonin receptor subtypes may be mediating the effects of serotonin in the suprachiasmatic nucleus, the location of the biological clock that generates the circadian rhythms. A single study in 1993 using the in vitro rat hypothalamic slice preparation suggested that serotonergic modulation of circadian rhythms at the level of the suprachiasmatic nucleus was acting via the newly discovered 5HT7 receptor subtype. Since that initial claim, serotonin modulation of circadian rhythms at the level of the suprachiasmatic nucleus has generally been attributed to 5HT7 receptor activation. However, when trying to cite relevant literature in support of 5HT7 involvement, it becomes evident that attributing rhythm-related serotonin activity in the suprachiasmatic nucleus to 5HT7 receptors may be somewhat premature. There are issues related to pharmacological specificity, species specific results, and significant knowledge gaps that necessitate a careful review of the literature to make a judgment as to whether 5HT7 receptors are responsible for serotonergic activity in the rodent suprachiasmatic nucleus. In addition, there is sufficient data available at present to make an initial determination as to the degree of 5HT7 receptor involvement at any level in the generation or modulation of circadian rhythms in rodent species. PMID- 11220775 TI - Serotonergic modulation of retinal input to the mouse suprachiasmatic nucleus mediated by 5-HT1B and 5-HT7 receptors. AB - Serotonin (5-HT) and 5-HT receptor agonists can modify the response of the mammalian suprachiasmatic nucleus (SCN) to light. It remains uncertain which 5-HT receptor subtypes mediate these effects. The effects of 5-HT receptor activation on optic nerve-mediated input to SCN neurons were examined using whole-cell patch clamp recordings in horizontal slices of ventral hypothalamus from the male mouse. The hypothesis that 5-HT reduces the effect of retinohypothalamic tract (RHT) input to the SCN by acting at 5-HT1B receptors was tested first. As previously described in the hamster, a mixed 5-HT(1A/1B) receptor agonist, 1-[3 (trifluoromethyl)phenyl]-piperazine hydrochloride (TFMPP), reduced the amplitude of glutamatergic excitatory postsynaptic currents (EPSCs) evoked by selectively stimulating the optic nerve of wild-type mice. The agonist was negligibly effective in a 5-HT1B receptor knockout mouse, suggesting minimal contribution of 5-HT1A receptors to the TFMPP-induced reduction in the amplitude of the optic nerve-evoked EPSC. We next tested the hypothesis that 5-HT also reduces RHT input to the SCN via activation of 5-HT7 receptors. The mixed 5-HT(1A/7) receptor agonist, R(+)-8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide (8-OH-DPAT), reduced the evoked EPSC amplitude in both wild-type and 5-HT1B receptor knockout mice. This effect of 8-OH-DPAT was minimally attenuated by the selective 5-HT1A receptor antagonist WAY 100635 but was reversibly and significantly reduced in the presence of ritanserin, a mixed 5-HT(2/7) receptor antagonist. Taken together with the authors' previous ultrastructural studies of 5-HT1B receptors in the mouse SCN, these results indicate that in the mouse, 5-HT reduces RHT input to the SCN by acting at 5-HT1B receptors located on RHT terminals. Moreover, activation of 5-HT7 receptors in the mouse SCN, but not 5-HT1A receptors, also results in a reduction in the amplitude of the optic nerve-evoked EPSC. The findings indicate that 5-HT may modulate RHT glutamatergic input to the SCN through 2 or more 5-HT receptors. The likely mechanism of altered RHT glutamatergic input to SCN neurons is an alteration of photic effects on the SCN circadian oscillator. PMID- 11220776 TI - What do reviewers really want? PMID- 11220778 TI - Fifty years of fun. PMID- 11220777 TI - Direct innervation of GnRH neurons by encephalic photoreceptors in birds. AB - In nonmammalian vertebrates, photic cues that regulate the timing of seasonal reproductive cyclicity are detected by nonretinal, nonpineal deep brain photoreceptors. It has long been assumed that the underlying mechanism involves the transmission of photic information from the photoreceptor to a circadian system, and thence to the reproductive axis. An alternative hypothesis is that there is direct communication between the brain photoreceptor and the reproductive axis. In the present study, light and confocal microscopy reveal that gonadotropin releasing hormone (GnRH) neurons and processes are scattered among photoreceptor cells (identified by their opsin-immunoreactivity) in the lateral septum (SL). In the median eminence (ME), opsin and GnRH immunoreactive fibers overlap extensively. Single and double label ultrastructural immunocytochemistry indicate that in the SL and preoptic area (POA), opsin positive terminals form axo-dendritic synapses onto GnRH dendrites. In the ME, opsin and GnRH terminals lie adjacent to each other, make contact with tanycytes, or terminate on the hypophyseal portal capillaries. These results reveal thatbrain photoreceptors communicate directly with GnRH-neurons; this represents a means by which photoperiodic information reaches the reproductive axis. PMID- 11220779 TI - Influence of light on feeding anticipatory activity in goldfish. AB - Most animals when presented with food on a periodic basis develop feeding anticipatory activity (FAA). The objective of the present study was to investigate the synchronization of activity rhythms to light and feeding in single goldfish given a single daily meal and exposed to different light regimes. In the 1st experiment, the group of fish fed at the end of the day showed a longer FAA (228 +/- 27 min) than the group fed 1 h after lights-on (97 +/- 31 min). In the 2nd experiment, goldfish under conflicting zeitgebers, LD (T = 26) and feeding (T = 24) cycles, initially synchronized to the light cycle although feeding time gradually assumed greater importance as the experiment progressed. In the 3rd experiment, after altering the feeding cycles by advancing or delaying feeding time by 4 h in LD 0.25:23.75, most goldfish resynchronized to the feeding stimulus and developed FAA. In conclusion, the authors' results revealed that FAA in goldfish is driven by an endogenous timing system that is entrainable by periodic feeding and influenced by the light regime. PMID- 11220780 TI - Differential effects of meal size and food energy density on feeding entrainment in goldfish. AB - The synchronizing stimulus, its transduction site, and the afferent pathways responsible for feeding entrainment remain unknown. In fish, the role of the diet in the development of feeding anticipatory activity (FAA) is not well understood and fundamental questions on the mechanisms of feeding entrainment, such as the meal characteristics required to develop FAA, remain unexplored. To test the entraining properties of daily meals with different sizes and energy densities, activity rhythms were studied after a 12-h shift of the feeding cycle in individual goldfish under constant light. In the 1st experiment, the energy content of a control diet (16.7 kJ/g) was diluted by replacing 50% (8.3 kJ/g) or 90% (1.7 kJ/g) of the diet with cellulose. However, the number of days required to stabilize FAA after the shift did not differ statistically between diets. In the 2nd experiment, meal size was modified by reducing the daily feeding ration to 0.5% and 0.1% b.wt.d(-1). In this case, differences in the entraining properties of the two feeding rations appeared because goldfish fed at 0.1% b.wt.d(-1) resynchronized faster than those fed at 0.5% b.wt.d(-1). These results revealed that the dilution of the dietary energy up to 1.7 kJ/g had no significant effect on the entraining properties of the feeding-entrainable oscillator (FEO), whereas the reduction of the meal size to 0.1% b.wt.d(-1) provoked a faster resynchronization after shifting the daily meal cycle. Taken together, these results suggest that gut distension may be involved in feeding entrainment, as a reduction in meal size but not in the amount of dietary energy supplied significantly shortened the time required for resynchronization and highlighted the different synchronizing properties of meal size and energy density as zeitgebers for the FEO. PMID- 11220781 TI - Scheduled voluntary wheel running activity modulates free-running circadian body temperature rhythms in Octodon degus. AB - Entrainment of the circadian pacemaker to nonphotic stimuli, such as scheduled wheel-running activity, is well characterized in nocturnal rodents, but little is known about activity-dependent entrainment in diurnal or crepuscular species. In the present study, effects of scheduled voluntary wheel-running activity on circadian timekeeping were investigated in Octodon degus, a hystricomorph rodent that exhibits robust crepuscular patterns of wakefulness. When housed in constant darkness, O. degus exhibited circadian rhythms in wheel-running activity and body temperature (Tb) with an average period length (tau) of 23.39 +/- 0.11 h. When wheel running was restricted to a fixed 2-h schedule every 24 h, tau increased on average 0.39 +/- 0.09 h but did not result in steady-state entrainment. Instead, relative coordination between the fixed running schedule and circadian timing was observed. Tau was greatest when scheduled wheel running occurred at CT 20.5 (0.4 h greater than DD baseline tau). Scheduled running activity also influenced Tb waveform symmetry, reflecting concomitant changes in the circadian activity-rest ratio (alpha:rho). Aftereffects of the scheduled wheel-running paradigm were also observed. In 2 animals, tau lengthened from 23.20 and 23.80 h to 24.14 and 24.15 h, respectively, and remained relatively stable for approximately 1 month during the wheel schedule. Although behavioral activity appears to be a weak zeitgeber in this species, these data suggest that nonphotic stimuli can phase delay the circadian pacemaker in O. degus at similar times of the day as in nocturnal hamsters and mice, and in humans. PMID- 11220782 TI - Low ambient temperature accelerates short-day responses in Siberian hamsters by altering responsiveness to melatonin. AB - Exposure to low ambient temperatures (Ta) accelerates appearance of the winter phenotype in Siberian hamsters transferred from long to short day lengths. Because melatonin transduces the effects of day length on the neuroendocrine axis, the authors assessed whether low Ta promotes the transition to winterlike traits by accelerating the onset of increased nocturnal melatonin secretion or by enhancing responsiveness to melatonin in short day lengths. Male hamsters were transferred from 16L (16 h light/day) to 8L (8 h light/day) photoperiods and held at 5 degrees C or 22 degrees C. Locomotor activity was recorded continuously, and body mass, testis size, and pelage color were determined biweekly for 8 weeks. The duration of nocturnal locomotion (alpha), a reliable indicator of the duration of nocturnal melatonin secretion, lengthened significantly earlier in hamsters exposed to a Ta of 5 degrees C than 22 degrees C. Cold exposure increased the proportion of hamsters that were photoresponsive: gonadal regression in short days increased from 44% at 22 degrees C to 81% at 5 degrees C (p < 0.05); low Ta did not, however, accelerate testicular regression in animals that were photoresponsive. Nonphotoresponsive animals at 5 degrees C temporarily had longer alphas during the first 4 weeks in short days and significant decreases in body mass and testicular size that were reversed during the ensuing weeks when alpha decreased. In a 2nd experiment, pinealectomized male hamsters infused for 10 h/day with melatonin for 2 weeks had significantly lower body and testes masses when maintained at 5 degrees C but not 22 degrees C. Low-ambient temperature appears to accelerate the appearance of the winter phenotype primarily by increasing target tissue responsiveness to melatonin and to a lesser extent by augmenting the rate at which the duration of nocturnal melatonin secretion increases in short day lengths. PMID- 11220783 TI - Effects of aging on the intrinsic circadian period of totally blind humans. AB - Age-related changes in the intrinsic circadian period (tau) have been hypothesized to account for sleep symptoms in the elderly such as early morning awakening. The authors sought to determine whether the aging process produced quantifiable differences in the tau of totally blind men who had free-running circadian rhythms. The melatonin onset was used as the indicator of circadian phase. Melatonin rhythms had been characterized about a decade previously when the participants were 38 +/- 6 (SD) years old. Both previous and current assessments of tau were derived from at least 3 serial measurements of the 24-h melatonin profile from which the melatonin onset was determined. All 6 participants exhibited a longer tau in the 2nd assessment (mean increase +/- SD of 0.13 +/- 0.08 h; p < 0.01). Four participants exhibited differences in tau with nonoverlapping 95% confidence intervals. The results do not support the commonly held view that tau shortens during human aging. On the contrary, tau appears to slightly, but significantly, lengthen during at least 1 decade in midlife. PMID- 11220784 TI - Perinatal expression of heat-shock protein 27 in brain regions and nonneural tissues of the piglet. AB - Important stressful events occur at birth or within the few hours that follow this event. To unravel a possible involvement of stress proteins, it is important to determine their levels of expression. Expression of HSP27 protein was determined by Western blotting in several nonneural tissues and in brain regions of the developing pig (fetal to adult). Maximum levels of expression were observed in heart, liver, and lung. In kidney, the expression was reduced during the first hours of life. Brain parts included whole brain, cerebellum, cortex, hippocampus, hypothalamus, and striatum. HSP27 immunogenicity was observed in all the brain regions studied. In whole brain, cerebellum, cortex, hippocampus, and hypothalamus extracts, the levels of HSP27 were decreased during the first hours of age (4 h to 2 d). In striatum, levels of expression were very low--if detectable--during the early postnatal days of life. Changes in environmental parameters, like temperature and/or hypoxia can be possibly related to differential expressions of HSPs, which can result in severe adverse developmental outcomes. The results are discussed in terms of using the newborn piglet as a model to study different forms of stress on the heat-shock protein postnatal expression. PMID- 11220785 TI - Localization of mRNAs for novel, atypical as well as conventional protein kinase C (PKC) isoforms in the brain of developing and mature rats. AB - Using in situ hybridization histochemistry, the localization of mRNAs for 10 isoforms of protein kinase C (PKC) in the rat brain was studied at embryonic and postnatal stages. In the embryonic brain, the gene expression was positive only for PKCepsilon, mu, lambda, and zeta with the former three more evident: The expression for PKCmu and lambda in the ventricular germinal zone and that for PKCepsilon, zeta, and lambda in the mantle zone. In the postnatal brain, the expression for PKCdelta, eta, and theta was detected differentially in a few circumscribed loci such as the thalamus, the habenula, the septum, and the cerebellar granule cells, whereas that for the other isoforms was seen widely in various loci of the gray matter with different intensity. The expression in the cerebellar external granule cell layer was positive only for PKCbeta (betaI and betaII), mu, and lambda with that for PKCbeta confined to its inner zone. There is a general tendency for all PKC isoforms that the expression levels reach at peaks in early postnatal brain and decreases more or less in adult specimens. This is the first report on the spatio-temporal heterogeneity in the gene expression for the whole members of PKC family in the brain throughout development, especially at embryonic days. PMID- 11220786 TI - Canavan's spongiform leukodystrophy: a clinical anatomy of a genetic metabolic CNS disease. AB - Canavan disease (CD) is a globally distributed early-onset leukodystrophy. It is genetic in nature, and results from an autosomally inherited recessive trait that is characterized by loss of the axon's myelin sheath while leaving the axons intact, and spongiform degeneration especially in white matter. There is also a buildup of N-acetyl-L-aspartate (NAA) in brain, as well as NAA acidemia and NAA aciduria. The cause of the altered NAA metabolism has been traced to several mutations in the gene for the production of aspartoacylase, located on chromosome 17, which is the primary enzyme involved in the catabolic metabolism of NAA. In this review, an attempt is made to correlate the change in NAA metabolism that results from the genetic defects in CD with the processes involved in the development of the CD syndrome. In addition, present efforts to counter the results of the genetic defects in this disease are also considered. PMID- 11220787 TI - Loss of oxidation-reduction specificity in amyotrophic lateral sclerosis associated CuZnSOD mutants. AB - Both transgenic mouse and cell culture models of familial amyotrophic lateral sclerosis (FALS) support a gain-of-function effect for the mutations in copper zinc superoxide dismutase (CuZnSOD) associated with FALS, but the nature of the function gained remains incompletely characterized. We previously reported an enhanced peroxidase activity for FALS-associated CuZnSOD mutants. Because one of the targets of such activity is CuZnSOD itself, we examined peroxide-mediated inactivation of wild-type and mutant CuZnSODs, and found that the mutants are more readily inactivated. Inactivation of the mutants was associated with fragmentation, which did not occur in the wild-type enzyme under these conditions. Furthermore, the reduction of the FALS-associated mutants by ascorbate was enhanced markedly when compared to the wild-type enzyme. The visible spectra of the mutants showed a consistent blue shift of the peak at 680 nm in the wild-type enzyme, suggesting an alteration in copper-site geometry. These results extend previous studies demonstrating enhanced peroxidase activity in the mutants, and suggest that the toxic function that leads to motor neuron degeneration may result from a loss of specificity of the redox reactions catalyzed by CuZnSOD. PMID- 11220788 TI - Pivotal role for acidic sphingomyelinase in cerebral ischemia-induced ceramide and cytokine production, and neuronal apoptosis. AB - Stroke is a major cause of long-term disability, the severity of which is directly related to the numbers of neurons that succumb to the ischemic insult. The signaling cascades activated by cerebral ischemia that may either promote or protect against neuronal death are not well understood. One injury-responsive signaling pathway that has recently been characterized in studies of non-neural cells involves cleavage of membrane sphingomyelin by acidic and/or neutral sphingomyelinase (ASMase) resulting in generation of the second messenger ceramide. We now report that transient focal cerebral ischemia induces large increases in ASMase activity, ceramide levels, and production of inflammatory cytokines in wild-type mice, but not in mice lacking ASMase. The extent of brain tissue damage is decreased and behavioral outcome improved in mice lacking ASMase. Neurons lacking ASMase exhibit decreased vulnerability to excitotoxicity and hypoxia, which is associated with decreased levels of intracellular calcium and oxyradicals. Treatment of mice with a drug that inhibits ASMase activity and ceramide production reduces ischemic neuronal injury and improves behavioral outcome, suggesting that drugs that inhibit this signaling pathway may prove beneficial in stroke patients. PMID- 11220790 TI - Musculoskeletal images. Bilateral insufficiency fracture of the femoral neck. PMID- 11220789 TI - Dietary restriction increases the number of newly generated neural cells, and induces BDNF expression, in the dentate gyrus of rats. AB - The adult brain contains neural stem cells that are capable of proliferating, differentiating into neurons or glia, and then either surviving or dying. This process of neural-cell production (neurogenesis) in the dentate gyrus of the hippocampus is responsive to brain injury, and both mental and physical activity. We now report that neurogenesis in the dentate gyrus can also be modified by diet. Previous studies have shown that dietary restriction (DR) can suppress age related deficits in learning and memory, and can increase resistance of neurons to degeneration in experimental models of neurodegenerative disorders. We found that maintenance of adult rats on a DR regimen results in a significant increase in the numbers of newly produced neural cells in the dentate gyrus of the hippocampus, as determined by stereologic analysis of cells labeled with the DNA precursor analog bromodeoxyuridine. The increase in neurogenesis in rats maintained on DR appears to result from decreased death of newly produced cells, rather than from increased cell proliferation. We further show that the expression of brain-derived neurotrophic factor, a trophic factor recently associated with neurogenesis, is increased in hippocampal cells of rats maintained on DR. Our data are the first evidence that diet can affect the process of neurogenesis, as well as the first evidence that diet can affect neurotrophic factor production. These findings provide insight into the mechanisms whereby diet impacts on brain plasticity, aging and neurodegenerative disorders. PMID- 11220791 TI - Soft-tissue images. Video-assisted thrombectomy of a mechanical prosthetic valve. PMID- 11220792 TI - Musculoskeletal case 14. Presentation. Multiple enchondromatosis. PMID- 11220793 TI - Soft-tissue case 37. Presentation. Recurrent gallbladder carcinoma along the laparoscopic cholecystectomy port track. PMID- 11220794 TI - Users' guides to the surgical literature: how to use an article about a diagnostic test. Evidence-Based Surgery Working Group. PMID- 11220795 TI - Carcinoid syndrome symposium on treatment modalities for gastrointestinal carcinoid tumours: symposium summary. AB - OBJECTIVE: To develop a collaborative approach for the treatment of gastrointestinal carcinoid tumours and carcinoid syndrome. PARTICIPANTS: Leaders in the medical, endocrine, radiologic and surgical treatment of carcinoid disease were selected to present papers at the Carcinoid Syndrome Symposium on Treatment Modalities for Gastrointestinal Carcinoid Tumours and participate in the workshop that followed. EVIDENCE: A multidisciplinary symposium with experts in the field of carcinoid syndrome was organized at the University of Calgary. Data presented, participation of the attendees and a review of the literature were used in the workshop to develop a collaborative approach to the management of carcinoid tumours. BENEFITS: Carcinoid tumours are rare and few centres have large experiences in their treatment. Before the development of this collaboration, patients with carcinoid tumours received a unidisciplinary approach depending on referral patterns. The development of a multidisciplinary neuroendocrine clinic helped to unify the approach to these patients, yet a consensus on the treatment of carcinoid tumours was lacking. The expertise at the symposium allowed for consensus and the development of treatment algorithms, including biochemical screening, radiographic localization and surgical intervention, for gastrointestinal carcinoid tumours. The role of medical and hormonal therapy after cytoreducion is presented. RECOMMENDATION: Patients with carcinoid tumours require a multidisciplinary approach to their care. PMID- 11220796 TI - The effects of a pneumatic tourniquet on blood loss in total knee arthroplasty. AB - OBJECTIVE: In lower-extremity surgery there are significant risks associated with the use of tourniquets. This prospective study was done to assess to what extent these risks may be offset by the potential advantages of tourniquets, namely reductions in blood loss, length of hospital stay and complication rates. DESIGN: A prospective case study. SETTING: A major urban hospital. PATIENTS: Sixty-three consecutive patients scheduled for primary cemented total knee arthroplasty (TKA) were blindly randomized into tourniqet (n = 33) and non-tourniquet (n = 30) groups. INTERVENTION: TKA during which a pneumatic tourniquet was applied or not applied to control blood loss. MAIN OUTCOME MEASURES: Perioperative blood loss, operating time, complication rates, hospital stay and transfusion needs. RESULTS: Differences in the total measured blood loss, intraoperative blood loss and the Hemovac drainage blood loss between the 2 groups were not significantly different (p > 0.25). The calculated total blood loss was actually lower in the non tourniquet group (p = 0.02). Between the groups there were no statistical differences in surgical time, length of hospital stay, transfusion requirements or rate of complications (although there was a trend to more complications in the tourniquet group (p = 0.06)). CONCLUSION: The effectiveness of a pneumatic tourniquet to control blood loss in TKA is questionable. PMID- 11220797 TI - Outpatient laparoscopic cholecystectomy: home visit versus telephone follow-up. AB - OBJECTIVES: To investigate the post-discharge follow-up required for patients who have undergone laparoscopic cholecystectomy on an outpatient basis and to determine if there was a significant difference in mean concern scores and satisfaction level of patients followed up by a home visit versus a telephone call. DESIGN: Prospective 2-group comparison. SETTING: A 221-bed acute care community hospital in western Canada. PATIENTS: One hundred and forty-nine patients who had undergone laparoscopic cholecystectomy and agreed to be discharged on the day of operation. INTERVENTIONS: Subjects were systematically allocated to receive either a home visit (HV, n = 72) or a telephone call (TC, n = 77) from a registered nurse on the evening of operation. During the follow-up, patient concerns were self-rated, interventions provided by the nurse were recorded, and nurses' perceptions of the need for the home visit were reported. A 48-hour telephone survey was used to determine patient satisfaction. OUTCOME MEASURES: Patient concern scores, patient satisfaction with follow-up, readmission rates and use of emergency room services within 30 days of operation. RESULTS: Subjects in the TC group had a significantly lower mean concern score (p < 0.001) and were significantly more satisfied with their follow-up (p = 0.034) than those in the HV group. Nurses perceived that 75% of the home visits were not necessary. Readmission rate was less than 1% (1 HV) and use of emergency room services was 6% (3 HV, 6 TC). CONCLUSIONS: Telephone contact is an acceptable method of follow-up for patients who have undergone outpatient laparoscopic cholecystectomy. The call should be made later in the evening on the day of operation or the next morning. PMID- 11220798 TI - RAVECAB: improving outcome in off-pump minimal access surgery with robotic assistance and video enhancement. AB - OBJECTIVE: To determine the efficacy of using the harmonic scalpel and robotic assistance to facilitate thoracoscopic harvest of the internal thoracic artery (ITA). DESIGN: A case series. SETTING: London Health Sciences Centre, University of Western Ontario, London, Ont. PATIENTS AND METHODS: Fifteen consecutive patients requiring harvest of the ITA for coronary artery bypass grafting. INTERVENTION: Robot-assisted, video-enhanced coronary artery bypass (RAVECAB) through limited-access incisions, using the harmonic scalpel and a voice activated robotic assistant. MAIN OUTCOME MEASURES: Ease and duration of the harvesting technique, complications of the procedure, graft flow and patency, and duration of postoperative hospitalization. RESULTS: RAVECAB facilitated thoracoscopic dissection of the ITA with the harmonic scalpel in all cases. There were no conversions to a standard approach and no reoperations for bleeding. The mean (and standard deviation) ITA harvest time was 64.1 (22.9) minutes (range from 40 to 118 minutes). Robotic voice command capture rate was greater than 95%. Mean (and SD) intraoperative graft flows were 33.1 (26.8) mL/min (range from 14 to 126 mL/min). There was 100% graft patency on postoperative angiography. There were no deaths, perioperaive myocardial infarction or arrhythmias. Mean (and SD) postoperative hospitalization was 3.3 (0.8) days. CONCLUSIONS: RAVECAB is a demanding procedure that addresses many of the disadvantages of the "conventional" minimally invasive coronary artery bypass. It allows complete pedicle dissection with minimal ITA manipulation and assures sufficient conduit length and a tension-free coronary artery anastomosis. All anastomoses were performed under direct vision through a 5- to 8-cm inferior mammary incision. PMID- 11220799 TI - Maintenance of certification program. PMID- 11220800 TI - Outcomes after the regionalization of major surgical procedures in the Alberta Capital Health Region (Edmonton). AB - OBJECTIVE: To evaluate the impact of regionalization on the outcomes of 16 surgical procedures performed in the Capital Health Region (Edmonton) of Alberta. DESIGN: A computer search of hospital discharge abstracts coded for the Canadian Institute for Health Information. SETTING: Two major hospitals in Edmonton. PATIENTS: The study population comprised 9250 patients (9727 procedures [4524, pre-regionalization, 5203 post-regionalization]) who underwent any of 16 major procedures in the 2 years before and the 2 years after restructuring. OUTCOME MEASURES: Demographic data, Charlson's comorbidity index, number of urgent and emergent cases, death rate, average length of hospital stay and the readmission rate. RESULTS: The post-regionalization patient group was slightly older, had a higher comorbidity index, and fewer urgent and emergent cases. The case volume increased by 15%, and 43.6% of patients used some form of community-based health care services. The median length of hospital stay decreased from 8.0 days pre regionalization to 7.0 days post-regionalization (p < 0.001). Overall and for specific procedures the death rate was unchanged (3.1% pre-regionalization, 2.4% post-regionalization, p = 0.06). The readmission rates were similar for both groups (8.0% versus 7.0%). CONCLUSIONS: The consolidation of these 16 major surgical procedures had minimal impact on death and readmission rates even though patients in the post-regionalization group were slightly older and had greater comorbidity. There was a significant decline in the length of hospital stay, which occurred nationally over the same period, and a corresponding increase in the use of community-based services. PMID- 11220801 TI - Reversible anastomotic stenosis after minimally invasive coronary artery bypass grafting. PMID- 11220802 TI - Instability resulting from a missed Chance fracture. PMID- 11220803 TI - Education versus service. PMID- 11220804 TI - Accessory bile duct in the gallbladder bed. PMID- 11220805 TI - "Who says there is a deficiency in care?". PMID- 11220806 TI - Curriculum for residents' education. PMID- 11220807 TI - The economic consequences of widowhood on elderly women in the United States and Germany. AB - PURPOSE: Different countries have different goals for social welfare policy. Consequently, it is reasonable to expect different outcomes after certain events. This article examines changes in the economic well-being of elderly women at widowhood in the United States and Germany. DESIGN AND METHODS: Longitudinal data from the U.S. Panel Study of Income Dynamics and the German Socioeconomic Panel were used to prepare a sample of elderly widows. Economic wellbeing the year before the husband's death was compared with economic well-being the year after the husband's death. RESULTS: Although the prevalence of poverty is different in the two countries, most widows in both countries experienced a decline in living standards, and many actually fell into poverty at widowhood. A fall in Social Security and pension income was the largest contributor to the fall in living standards. IMPLICATIONS: The retirement income system in both countries seems to be adequate for married couples but appears to fail for widows. PMID- 11220808 TI - Ageism, age relations, and garment industry work in Montreal. AB - This study examined the complexities of age relations at work. Garment workers believed that their fate was linked to ageism and that their work experience was discounted by management. Managers wanted to be rid of older workers because they commanded higher wages than younger workers. The issue was cost reduction, and age was implicated unintendedly. Still, managers seemed to use stereotypical images to discourage older workers and they did not organize work routines to facilitate the adaptation of them. Instead, they subcontracted the easy jobs, relying on the experience of the older employees for difficult work while not adapting the workplace. Theoretically, the authors argue that ageism and age discrimination can best be understood through a recognition of the importance of structured age relations and human agency. PMID- 11220809 TI - Preference for place of death in a continuing care retirement community. AB - PURPOSE: To describe death-related planning and preferences for place of death among well elders in a community characterized by a low rate of hospital deaths. DESIGN AND METHODS: Cross-sectional prevalence survey of independent-living residents (n = 219) of a continuing-care retirement community (CCRC) in Central North Carolina characterized by a low rate of hospital deaths. RESULTS: Death related planning played a part in the decision of 40% of residents to move to the CCRC. A majority of residents reported a clear preference for place of death, and a majority of these preferred to die on the CCRC campus. Most residents wanted to discuss their preferences for place of death with their health care provider. Preferences for place of death appear consistent across age cohorts and are relevant to elders' long-term care decisions. IMPLICATIONS: Given the striking discrepancy between patients' preferences for nonhospital deaths and the high prevalence of hospital deaths in the United States, this often-neglected issue should be routinely addressed in end-of-life planning. The CCRC may be a practice model that is particularly compatible with personal preferences for place of death. PMID- 11220810 TI - Extending gerontological research through linking investigators' studies to public-use datasets. AB - PURPOSE: Public-use datasets can extend data collected by individual investigators in various ways: making external comparisons, providing additional data on individual respondents, and creating internal comparison groups. The authors describe the advantages and limitations of these methods and practical and conceptual issues in combining investigator-initiated and public-use datasets. DESIGN AND METHODS: These issues are illustrated with a study of functional decline among 674 patients following hospitalization for hip fracture that was augmented with data from a public-use dataset, the Established Populations for Epidemiologic Studies of the Elderly (EPESE). RESULTS: By creating an internal comparison group of EPESE respondents, frequency matched to hip fracture patients on age, sex, and baseline functional limitations, the authors formed a single dataset and performed multivariable analyses of factors associated with functional decline. IMPLICATIONS: Gerontological research may benefit by applying these methods to program evaluations and longitudinal analyses of health outcomes with numerous public-use datasets. PMID- 11220811 TI - Want to understand how Americans viewed long-term care in 1998? Start with media coverage. AB - PURPOSE: This analysis describes media coverage of long-term care in 1998. DESIGN AND METHODS: Several sources were used to place coverage of long-term care in 1998 in the context of recent years and other health issues. For the primary analysis, stories in which long-term care was a major topic were collected from Lexis-Nexis Academic Universe. Media sources included major newspapers, network news, CNN, and NPR. Stories were coded for topic, details about the topic, physical placement within the overall coverage, and underlying issues. RESULTS: A small percentage of media coverage in 1998 concerned long-term care. Among long term care topics, nursing homes received the most coverage. A small percentage of long-term care topics were reported on the front page, and few underlying issues framed these topics. IMPLICATIONS: To ensure that Americans receive a comprehensive view of long-term care issues, gerontologists must work with reporters to influence how they report on long-term care. PMID- 11220812 TI - Medicaid estate planning: perceptions of morality and necessity. AB - PURPOSE: Although several studies have examined the magnitude and prevalence of Medicaid estate planning (MEP), little is known about factors that influence individual behaviors in this area. Normative data regarding public perceptions of and motivations for MEP are nonexistent. This study explored views about MEP among community-dwelling older adults and family caregivers. DESIGN AND METHODS: Eighteen focus groups were completed (N = 155), with a stratified homogeneous sample to ensure representation from individuals of varying race/ethnicity, experience with nursing home and home care services, and socioeconomic status. Analyses of transcripts were completed with NUD*IST 4.0 software. RESULTS: Disincentives for MEP included losing control of one's assets, Medicaid stigma, and perceived immorality of MEP. Incentives for MEP included preservation of one's estate and protection of a spouse. Finally, variability in accessibility to and awareness of MEP was described. IMPLICATIONS: This exploratory study identifies motivations for individual behaviors and describes evolving social norms regarding MEP; implications for policy and research are discussed. PMID- 11220813 TI - A randomized, controlled trial of a home environmental intervention: effect on efficacy and upset in caregivers and on daily function of persons with dementia. AB - PURPOSE OF STUDY: The authors determined short-term effects of a home environmental intervention on self-efficacy and upset in caregivers and daily function of dementia patients. They also determined if treatment effect varied by caregiver gender, race, and relationship to patient. DESIGN AND METHODS: Families (N = 171) of dementia patients were randomized to intervention or usual care control group. The intervention involved 5 90-min home visits by occupational therapists who provided education and physical and social environmental modifications. RESULTS: Compared with controls, intervention caregivers reported fewer declines in patients' instrumental activities of daily living (p = .030) and less decline in self-care and fewer behavior problems in patients at 3 months post-test. Also, intervention spouses reported reduced upset (p = .049), women reported enhanced self-efficacy in managing behaviors (p = .038), and women (p = .049) and minorities (p = .037) reported enhanced self-efficacy in managing functional dependency. IMPLICATIONS: The environmental program appears to have a modest effect on dementia patients' IADL dependence. Also, among certain subgroups of caregivers the program improves self-efficacy and reduces upset in specific areas of caregiving. PMID- 11220814 TI - Aging in place in assisted living: philosophy versus policy. AB - PURPOSE: Support of older adults' capacity to age in place is a core concept of the assisted living philosophy. This research examined implementation of the aging-in-place philosophy in 1 midwestern state (Kansas). DESIGN AND METHODS: This study was part of a larger state agency and university collaborative project to examine admission and discharge policies in these settings. Data analysis was conducted with descriptive statistics. Kansas findings were compared to national findings. RESULTS: Residents' capacity to age in place was limited by facility admission and discharge policies that were more restrictive than state regulations in the areas of behavioral problems, incontinence, and cognition. In general, assisted living facility policies in Kansas were more restrictive than admission and discharge policies found nationally. IMPLICATIONS: More inclusive assisted living admission and discharge criteria, and concomitant staffing and funding, are necessary if the aging-in-place philosophy is to be more fully implemented. PMID- 11220815 TI - Support for physician-assisted suicide: exploring the impact of ethnicity and attitudes toward planning for death. AB - The authors interviewed adults in five ethnic groups, used factor analysis to quantify attitudes toward planning for death, and used path analysis to test the relative influence of respondent characteristics, including ethnicity, and attitude factors (Advocacy to Discuss/Document Wishes, Trust in Family and Physician to Make Decisions, Reliance on Religious Guidance, Fears and Anxiety About Life's End, and Fatalism About Death's Timing) on support for physician assisted suicide (PAS). Findings verified that attitude factors had a direct effect on PAS support but that, contrary to the hypothesis, ethnicity had a direct effect on support for PAS as well. PMID- 11220816 TI - Data from long-term care ombudsman programs in six states: the implications of collecting resident demographics. AB - PURPOSE: This article focuses on why it is important for longterm care ombudsmen to collect resident demographics. DESIGN AND METHODS: The authors analyzed a cross-sectional, 6-state database to show the importance of ombudsman programs' collecting demographic information about the residents of long-term care facilities whom they serve. To demonstrate the importance of collecting demographic data about residents, the authors examined the relationships between race, gender, and types of complaints lodged, verified, and fully resolved. RESULTS: A higher percentage of complaints lodged on behalf of racial minorities was verified, yet a lower percentage was fully resolved. IMPLICATIONS: Ombudsman databases are a potential resource for identifying residents' characteristics that increase their vulnerability in long-term care settings. PMID- 11220817 TI - The unique contribution of key existential factors to the prediction of psychological well-being of older adults following spousal loss. AB - PURPOSE: This study examined the unique contribution of key existential factors to the prediction of psychological well-being of older adults following spousal loss. DESIGN AND METHOD: A number of measures to assess psychological well-being, sociodemographic standing, social resources, and religious and spiritual resources were administered to a volunteer sample of widows and widowers to test the hypothesis that existential factors such as personal meaning, religiosity, and spirituality are more potent predictors of psychological well-being than are previously hypothesized variables of sociodemographic, social support, and physical factors. RESULTS: A hierarchical regression analysis of the data supported the hypothesis that existential factors are major contributors to psychological well-being of older adults following spousal loss. Findings showed that widowers, compared to widows, scored lower on the measure of psychological well-being. IMPLICATIONS: Implications of the findings are discussed for practitioners working with bereaved spouses; suggestions for further research concerning bereavement and psychological well-being are made. PMID- 11220819 TI - Reminiscence, personality, and psychological functioning in older adults. AB - PURPOSE: The present study examined the relationships between the frequency and functions of reminiscence, personality styles, and psychological functioning. There is little research on the psychological factors that correlate with reminiscence, especially in relationship to clinical constructs such as depression and anxiety. Research in the area of reminiscence functions may facilitate a better understanding of the factors affecting change in reminiscence therapies. DESIGN AND METHODS: Seventy-seven healthy older adults completed the following self-report scales: Reminiscence Functions Scale, NEO Five Factor Personality Inventory, Beck Depression Inventory-Second Edition, State-Trait Anxiety Inventory, and the Templer-McMordie Death Anxiety Scale. RESULTS: Using canonical correlation techniques, results indicated that individuals with negative psychological functioning frequently reminisce as a way to refresh bitter memories, reduce boredom, and prepare for death. IMPLICATIONS: The present study provides implications for both researchers and clinicians. Contrary to previous studies, results indicate that depressed and anxious older adults commonly use reminiscence and therefore may be appropriate candidates for reminiscence treatments. PMID- 11220818 TI - Unmet need for personal assistance with activities of daily living among older adults. AB - PURPOSE: This study examined the prevalence, correlates, and negative consequences of unmet need for personal assistance with activities of daily living (ADLs) among older adults. DESIGN AND METHODS: The authors analyzed cross sectional data from the 1994 National Health Interview Survey's Supplement on Aging. Data were weighted to be representative of the noninstitutionalized population aged 70 years and older. RESULTS: Overall, 20.7% of those needing help to perform 1 or more ADLs (an estimated 629,000 persons) reported receiving inadequate assistance; for individual ADLs, the prevalence of unmet need ranged from 10.2% (eating) to 20.1% (transferring). The likelihood of having 1 or more unmet needs was associated with lower household income, multiple ADL difficulties, and living alone. Nearly half of those with unmet needs reported experiencing a negative consequence (e.g., unable to eat when hungry) as a result of their unmet need. IMPLICATIONS: Greater, targeted efforts are needed to reduce the prevalence and consequences of unmet need for ADL assistance in elderly persons. PMID- 11220821 TI - 2000 Winter Conference on Plasma Spectrochemistry--a time to refresh. PMID- 11220822 TI - Development of an ICP-IDMS method for accurate routine analyses of toxic heavy metals in polyolefins and comparison with results by TI-IDMS. AB - An inductively coupled plasma isotope dilution mass spectrometric (ICP-IDMS) method was developed as a suitable method - with respect to its sensitivity, precision, accuracy, and time-consumption - for the analysis of toxic heavy metal traces (Pb, Cd, Cr, and Hg) in polyolefins. Results for Pb, Cd, and Cr were compared with those obtained by thermal ionization isotope dilution mass spectrometry (TI-IDMS), which was used as a reference method. Because of its high first ionization potential and its high volatility mercury could not be determined by TI-IDMS. A multi-element spike solution, containing isotopically enriched 206Pb, 116Cd, 53Cr, and 201Hg, was used for the isotope dilution step. Decomposition of the polyolefin samples was carried out with concentrated HNO3 at temperatures of about 300 degrees C in a high pressure asher (HPA). This procedure decomposes polyolefins completely and allows isotopic equilibration between sample and spike isotopes. Detection limits of 16 ng/g, 5 ng/g, 164 ng/g, and 9 ng/g were obtained for Pb, Cd, Cr, and Hg by ICP-IDMS using only sample weights of 0.25 g. In different commercially available polyethylene samples heavy metal concentrations in the range of < 5 ng/g to 4 x 10(3) ng/g were analyzed. Both mass spectrometric methods were applied within the EU project "Polymeric Elemental Reference Material (PERM)" for the certification of two polyethylene reference materials. The ICP-IDMS results agreed very well with those of TI-IDMS which demonstrates the accuracy of the ICP-IDMS method also suitable for routine analyses. PMID- 11220820 TI - "Going home" or "leaving home"? The impact of person and place ties on anticipated counterstream migration. AB - PURPOSE: The probability of anticipated return migration in retirees is explored. DESIGN AND METHODS: Survey data were analyzed from interviews with a sample of elderly European Americans who migrated to a metropolitan city on Florida's east coast following retirement. RESULTS: Results are consistent with the specification of the 2nd move in E. Litwak and C. F. Longino's (1987) life course model of retirement migration. Respondents were unlikely to anticipate a return move unless ties to the back home community made such a move possible. IMPLICATIONS: Ties with children, both back home and in Florida, significantly influence consideration of a return move. PMID- 11220823 TI - Isotope dilution inductively coupled plasma quadrupole mass spectrometry in connection with a chromatographic separation for ultra trace determinations of platinum group elements (Pt, Pd, Ru, Ir) in environmental samples. AB - An isotope dilution inductively coupled plasma quadrupole mass spectrometric (ID ICP-QMS) method was developed for the simultaneous determination of the platinum group elements Pt, Pd, Ru, and Ir in environmental samples. Spike solutions, enriched with the isotopes 194Pt, 108Pd, 99Ru, and 191Ir, were used for the isotope dilution step. Interfering elements were eliminated by chromatographic separation using an anion-exchange resin. Samples were dissolved with aqua regia in a high pressure asher. Additional dissolution of possible silicate portions by hydrofluoric acid was usually not necessary. Detection limits of 0.15 ng x g(-1), 0.075 ng x g(-1), and 0.015 ng x g(-1) were achieved for Pt, Pd, Ru, and Ir, respectively, using sample weights of only 0.2 g. The reliability of the ID-ICP QMS method was demonstrated by analyzing a Canadian geological reference material and by participating in an interlaboratory study for the determination of platinum and palladium in a homogenized road dust sample. Surface soil, sampled at different distances from a highway, showed concentrations in the range of 0.1 87 ng x g(-1). An exponential decrease of the platinum and palladium concentration with increasing distance and a small anthropogenic contribution to the natural background concentration of ruthenium and iridium was found in these samples. PMID- 11220825 TI - Mass spectrometry with plasma sources at atmospheric pressure--state-of-the-art and some developmental trends. AB - The state-of-the art and trends of development in ICP-MS are presented. Special reference is made to progress in plasma sources, which can be used as ion sources and, especially, the inductively coupled plasma and new microwave plasma sources. Further, progress in sample introduction for plasma mass spectrometry is discussed with special reference to new pneumatic nebulizers, enabling, e.g., work with microflows of solutions at high efficiency, new developments in ultrasonic nebulization, in electrothermal evaporation, laser ablation and hydride generation. Innovation in the types of mass spectrometers used is discussed with special reference to the use of reaction and collision cells, sector field mass spectrometry, time-of-flight mass spectrometry and multicollector mass spectrometers. Challenging applications in the field of speciation, especially in environmental samples with the example of the chromium speciation, and in materials analysis, with special reference to the analysis of ceramic powders with and without on-line matrix removal, are also discussed. PMID- 11220826 TI - Precise and accurate isotope ratio measurements by ICP-MS. AB - The precise and accurate determination of isotope ratios by inductively coupled plasma mass spectrometry (ICP-MS) and laser ablation ICP-MS (LA-ICP-MS) is important for quite different application fields (e.g. for isotope ratio measurements of stable isotopes in nature, especially for the investigation of isotope variation in nature or age dating, for determining isotope ratios of radiogenic elements in the nuclear industry, quality assurance of fuel material, for reprocessing plants, nuclear material accounting and radioactive waste control, for tracer experiments using stable isotopes or long-lived radionuclides in biological or medical studies). Thermal ionization mass spectrometry (TIMS), which used to be the dominant analytical technique for precise isotope ratio measurements, is being increasingly replaced for isotope ratio measurements by ICP-MS due to its excellent sensitivity, precision and good accuracy. Instrumental progress in ICP-MS was achieved by the introduction of the collision cell interface in order to dissociate many disturbing argon-based molecular ions, thermalize the ions and neutralize the disturbing argon ions of plasma gas (Ar+). The application of the collision cell in ICP-QMS results in a higher ion transmission, improved sensitivity and better precision of isotope ratio measurements compared to quadrupole ICP-MS without the collision cell [e.g., for 235U/238U approximately 1 (10 microg x L(-1) uranium) 0.07% relative standard deviation (RSD) vs. 0.2% RSD in short-term measurements (n = 5)]. A significant instrumental improvement for ICP-MS is the multicollector device (MC-ICP-MS) in order to obtain a better precision of isotope ratio measurements (with a precision of up to 0.002%, RSD). CE- and HPLC-ICP-MS are used for the separation of isobaric interferences of long-lived radionuclides and stable isotopes by determination of spallation nuclide abundances in an irradiated tantalum target. PMID- 11220824 TI - Arsenic metabolism in seaweed-eating sheep from Northern Scotland. AB - Cation exchange and anion exchange liquid chromatography were coupled to an ICP MS and optimised for the separation of 13 different arsenic species in body fluids (arsenite, arsenate, dimethylarsinic acid (DMAA), monomethylarsonic acid (MMAA), trimethylarsine oxide (TMAO), tetramethylarsonium ion (TMA), arsenobetaine (AsB), arsenocholine (AsC), dimethylarsinoyl ethanol (DMAE) and four common dimethylarsinoylribosides (arsenosugars). The arsenic species were determined in seaweed extracts and in the urine and blood serum of seaweed-eating sheep from Northern Scotland. The sheep eat 2-4 kg of seaweed daily which is washed ashore on the most northern Island of Orkney. The urine, blood and wool of 20 North Ronaldsay sheep and kidney, liver and muscle from 11 sheep were sampled and analysed for their arsenic species. In addition five Dorset Finn sheep, which lived entirely on grass, were used as a control group. The sheep have a body burden of approximately 45-90 mg arsenic daily. Since the metabolism of arsenic species varies with the arsenite and arsenate being the most toxic, and organoarsenic compounds such as arsenobetaine the least toxic compounds, the determination of the arsenic species in the diet and their body fluids are important. The major arsenic species in their diet are arsenoribosides. The major metabolite excreted into urine and blood is DMAA (95 +/- 4.1%) with minor amounts of MMAA, riboside X, TMA and an unidentified species. The occurrence of MMAA is assumed to be a precursor of the exposure to inorganic arsenic, since demethylation of dimethylated or trimethylated organoarsenic compounds is not known (max. MMAA concentration 259 microg/L). The concentrations in the urine (3179 +/- 2667 microg/L) and blood (44 +/- 19 microg/kg) are at least two orders of magnitude higher than the level of arsenic in the urine of the control sheep or literature levels of blood for the unexposed sheep. The tissue samples (liver: 292 +/- 99 microg/kg, kidney: 565 +/- 193 microg/kg, muscle: 680 +/- 224 microg/kg) and wool samples (10470 +/- 5690 microg/kg) show elevated levels which are also 100 times higher than the levels for the unexposed sheep. PMID- 11220827 TI - Bulk analysis by IR laser ablation inductively coupled plasma atomic emission spectrometry. AB - Two laser ablation systems dedicated to bulk analysis were evaluated for steel and PVC samples, using inductively coupled plasma atomic emission spectrometry detection. These systems were characterized by the use of a Nd:YAG laser operating at 1064 nm, the absence of observation device and a large laser spot size. The 1064 nm wavelength was selected to avoid the use of frequency multiplying optics, and to be less critical to the sampling position. Calibration graphs and limits of detection are given for both types of materials. LODs were in the range 3-120 microg/g for steel, and in the range 0.07-15 microg/g for PVC. In the case of steel samples, similar calibration graph slopes were obtained between polished and unpolished samples. PMID- 11220828 TI - Optimization of a laser ablation-inductively coupled plasma "time of flight" mass spectrometry system for short transient signal acquisition. AB - Simultaneous ion sampling and sequential detection offered by inductively coupled plasma 'time of flight' mass spectrometry (ICP-TOFMS) provides advantages for the analysis of short transient concentration-variable signals as produced in laser ablation. In order to investigate the capabilities of ICP-TOFMS in combination with an excimer laser ablation system, ablation studies on reference materials and geological samples were carried out. Various ICP-TOFMS parameters were optimized for laser-induced aerosols. Transverse rejection ion pulse was used to extend the dynamic range in concentration. A reduced volume ablation cell was designed and used in order to increase the sample density in the ICP. Results for 63 simultaneously measured isotopes (SRM 610 from NIST) lead to limits of detection in the 1-100 microg/g range for a 80 microm crater diameter (10 Hz, 1.2 mJ pulse energy). The reproducibility of signal ratios was determined to be better than 2% RSD for transient signals using 102 ms integration time. These optimized parameters were then used for the analysis of tin-rich fluid inclusions. Preliminary results of multielement analysis and isotopic ratio determinations on individual fluid inclusions (63 isotopes, 102 ms integration time) demonstrate the capabilities of ICP-TOFMS in combination with laser ablation. PMID- 11220829 TI - Recent trends and developments in laser ablation-ICP-mass spectrometry. AB - The increased interest in laser technology (e.g. for micro-machining, for medical applications, light shows, CD-players) is a tremendous driving force for the development of new laser types and optical set-ups. This directly influences their use in analytical chemistry. For direct analysis of the elemental composition of solids, mostly solid state lasers, such as Nd:YAG laser systems operating at 1064 nm (fundamental wavelength), 266 nm (frequency quadrupled) and even 213 nm (frequency quintupled) have been investigated in combination with all available inductively coupled plasma mass spectrometers. The trend towards shorter wavelengths (1064 nm - 157 nm) was initiated by access to high quality optical materials which led to the incorporation of UV gas lasers, such as excimer lasers (XeCl 308 nm, KrF 248 nm, ArF 193 nm, and F2 157 nm) into laser ablation set-ups. The flexibility in laser wavelengths, output energy, repetition rate, and spatial resolution allows qualitative and quantitative local and bulk elemental analysis as well as the determination of isotope ratios. However, the ablation process and the ablation behavior of various solid samples are different and no laser wavelength was found suitable for all types of solid samples. This article highlights some of the successfully applied systems in LA-ICP-MS. The current fields of applications are explained on selected examples using 266 nm and 193 nm laser ablation systems. PMID- 11220830 TI - A possible steady state kinetic model for the atomization and excitation processes during inductively coupled plasma atomic emission spectrometry: application to interference effects of lithium on calcium. AB - A possible steady state kinetic model is presented for the atomization and excitation processes during inductively coupled plasma atomic emission spectrometry. The model takes into account the relative rates of (a) thermal dissociation of analyte salt, (b) recombination of counter atom and analyte atoms, (c) charge transfer between analyte and interferent species, (d) charge transfer between analyte and argon species, and (e) ion/electron collisional de ionization. Number density ratio data, n(u)'/n(u), where n(u) denotes the excited state and the prime denotes the presence of an interferent element, are presented showing that the predictions of the model are consistent with the signal enhancement observed at low analyte concentrations when Ca is determined by ICP in the presence of excess Li. PMID- 11220831 TI - A novel high-temperature (360 degrees C)/high-pressure (30 MPa) flow system for online sample digestion applied to ICP spectrometry. AB - A flow injection sample digestion system has been developed comprising an indirectly electrically heated Pt/Ir capillary. Such a capillary allows reaction temperatures of up to 360 degrees C and pressures of up to 30 MPa (300 bar) and withstands concentrated acids. This temperature is 130 degrees C to 160 degrees C higher compared to the operating temperatures of microwave heated flow systems. A combination of an ultrasonic nebulizer and membrane desolvator serves as an interface between the flow digestion system and an ICP/AES spectrometer. The membrane desolvator removes interfering gaseous digestion products so effectively before the sample stream enters the plasma that the measured residual carbon concentration falls in the region of the detection limit of ICP/OES measurements. Sewage sludge samples were digested using nitric acid and the elemental traces online determined. The detection limits related to the original dry substances amount to the lower microg/g range. PMID- 11220832 TI - A simple co-precipitation inductively coupled plasma mass spectrometric method for the determination of uranium in seawater. AB - Inductively coupled plasma mass spectrometry (ICP-MS) was used in the determination of 238uranium in seawater after concentration by a simplified co precipitation with iron hydroxide. Ocean water and reference seawater were used in the study. The co-precipitation method required a smaller sample volume (10 fold less), and less column separation to recover the uranium from the seawater matrix, compared to the original iron hydroxide method. The direct seawater dilution technique requires only a small seawater volume (0.5 mL) and offers a rapid, reliable method for uranium analysis in seawater compared to traditional methods. Comparison of the results for simple co-precipitation, direct dilution of seawater, and theoretical uranium values based on salinity concentrations, yielded negligible differences. Data from this work show that the certified value for NASS-4 is low. PMID- 11220833 TI - Speciation of antimony(III) and antimony(V) in cell extracts by anion chromatography/inductively coupled plasma mass spectrometry. AB - An analytical method for the separation and quantification of Sb(III) and Sb(V) using anion chromatography with ICP-MS is presented. The optimum conditions for the separation of the antimony species were established with 15 mmol/L nitric acid at pH 6 as eluent system on a PRP-X100 column. The retention times for antimony(V) and antimony(III) were 85 s and 300 s with detection limits of 0.06 microg/L and 0.29 microg/L, respectively. The proposed method was applied to cell extracts of Leishmania donovani, which were incubated with antimony(III) and antimony(V). Some metabolism seemed to occur within the cells. PMID- 11220834 TI - A new HG/LT-GC/ICP-MS multi-element speciation technique for real samples in different matrices. AB - An improved speciation technique is presented for metal(loid)organic compounds, enabling identification and quantification of species from twelve elements: germanium, arsenic, selenium, molybdenum, tin, antimony, tellurium, iodine, tungsten, mercury, lead and bismuth. At this time it is possible to identify 29 species with boiling points between -88.5 degrees C and 250 C in gaseous, liquid and solid samples in a few minutes. This study shows as an example results from measurements of soil samples from municipal waste deposits. The HG/LT-GC/ICP-MS (hydride generation/low temperature-gas chromatography/inductively coupled plasma mass spectrometry) apparatus contains a home-built gas chromatograph that enables satisfactory separation of various species with a boiling point difference of > or = 14 degrees C. The absolute detection limits for the elements mentioned above were below 0.7 pg. PMID- 11220835 TI - Automated in situ trace element analysis of silicate materials by laser ablation inductively coupled plasma mass spectrometry. AB - This paper describes the automated in situ trace element analysis of solid materials by laser ablation (LA) inductively coupled plasma mass spectrometry (ICP-MS). A compact computer-controlled solid state Nd:YAG Merchantek EO UV laser ablation (LA) system has been coupled with the high sensitivity VG PQII S ICP-MS. A two-directional communication was interfaced in-house between the ICP-MS and the LA via serial RS-232 port. Each LA-ICP-MS analysis at a defined point includes a 60 s pre-ablation delay, a 60 s ablation, and a 90 s flush delay. The execution of each defined time setting by LA was corresponding to the ICP-MS data acquisition allowing samples to be run in automated cycle sequences like solution auto-sampler ICP-MS analysis. Each analytical cycle consists of four standards, one control reference material, and 15 samples, and requires about 70 min. Data produced by Time Resolved Analysis (TRA) from ICP-MS were later reduced off-line by in-house written software. Twenty-two trace elements from four reference materials (NIST SRM 613, and fused glass chips of BCR-2, SY-4, and G-2) were determined by the automated LA-ICP-MS method. NIST SRM 610 or NIST SRM 613 was used as an external calibration standard, and Ca as an internal standard to correct for drift, differences in transport efficiency and sampling yield. Except for Zr and Hf in G-2, relative standard deviations for all other elements are less than 10%. Results compare well with the data reported from literature with average limits of detection from 1 ng x g(-1) to 455 ng x g(-1) and less than 100 ng x g(-1) for most trace elements. PMID- 11220836 TI - Determination of trace elements in zeolites by laser ablation ICP-MS. AB - Laser ablation inductively coupled plasma mass spectrometry using a quadrupole based mass spectrometer (LA-ICP-QMS) was applied for the analysis of powdered zeolites (microporous aluminosilicates) used for clean-up procedures. For the quantitative determination of trace element concentrations three geological reference materials, granite NIM-G, lujavrite NIM-L and syenite NIM-S, from the National Institute for Metallurgy (South Africa) with a matrix composition corresponding to the zeolites were employed. Both the zeolites and reference materials were fused with a lithium borate mixture to increase the homogeneity and to eliminate mineralogical effects. In order to compare two different approaches for the quantification of analytical results in LA-ICP-MS relative sensitivity coefficients (RSCs) of chemical elements and calibration curves were measured using the geostandards. The experimentally obtained RSCs are in the range of 0.2-6 for all elements of interest. Calibration curves for trace elements were measured without and with Li or Ti as internal standard element. With a few exceptions the regression coefficients of the calibration curves are better than 0.993 with internal standardization. NIM-G granite reference material was employed to evaluate the accuracy of the technique. Therefore, the measured concentrations were corrected with RSCs which were determined using lujavrite reference material NIM-L. This quantification method provided analytical results with deviations of 1-11% from the recommended and proposed values in granite reference material NIM-G, except for Co, Cs, La and Tb. The relative standard deviation (RSD) of the determination of the trace element concentration (n = 5) is about 1% to 6% using Ti as internal standard element. Detection limits of LA ICP-QMS in the lower microg/g range (from 0.03 microg/g for Lu, Ta and Th to 7.3 microg/g for Cu, with the exception of La) have been achieved for all elements of interest. Under the laser ablation conditions employed (lambda: 266 nm, repetition frequency: 10 Hz, pulse energy: 10 mJ, laser power density: 6 x 10(9) W/cm2) fractionation effects of the determined elements relative to the internal standard element Ti were not observed. PMID- 11220837 TI - Ion chromatography inductively coupled plasma mass spectrometry (IC-ICP-MS) and radiometric techniques for the determination of actinides in aqueous leachate solutions from uranium oxide. AB - The choice of the analytical method for the determination of actinide isotopes in leachate solutions has to be made considering several parameters: detection limit for each isotope, sample preparation procedure in terms of duration and complexity, counting time and interferences. A leachate solution obtained by keeping a pellet of UO2 doped with 238Pu in contact with distilled water was investigated for the content of U and Pu isotopes by radiometric methods (alpha-, gamma-spectrometry and liquid scintillation counting). The results of the radiometric methods were compared with those obtained from the analysis performed by inductively coupled plasma mass spectrometry on-line to a system for chromatographic separation (IC-ICP-MS). The comparison confirmed that IC-ICP-MS is a powerful method for the detection of long-lived radionuclides. The radiometric methods have a detection limit two orders of magnitude lower than IC ICP-MS in the case of short-lived radioisotopes mostly due to the low background in the detector. On the other hand, the sample preparation and the analysis duration are more time-consuming compared to IC-ICP-MS; moreover, not all isotopes can be determined by using only one radiometric technique. PMID- 11220838 TI - Comparison between the use of direct current glow discharge mass spectrometry and inductively coupled plasma quadrupole mass spectrometry for the analysis of trace elements in nuclear samples. AB - The quantitative determination of trace elements in nuclear samples by GDMS and ICP-MS is presented and compared. Spectral interferences, matrix effects, detection limits, precision and accuracy are discussed. Results for selected samples demonstrated that both techniques are complementary. The use of a multi standard solution provides the most accurate results in ICP-MS, whereas in GDMS this is achieved by relative sensitivity factors (RSF) matrix matched. Nevertheless, the use of standard RSF allows a fast screening. PMID- 11220839 TI - Effective management of daytime wetting. AB - Voiding dysfunction is important in the genesis of wetting and urinary tract infections but cure is not often achieved with the brief interventions possible from a busy outpatient clinic. Our aim was to establish a planned programme of care based on a physiological and psychological assessment. We studied 100 children: 70 per cent had daytime enuresis; 11 per cent nocturnal enuresis alone and 19 per cent had recurrent urinary tract infections. Following assessment we found that 48 per cent had a significant post micturition residue. After six months of treatment 79 per cent were either completely dry or had only an occasional accident. Treatment for this condition is usually considered to be very time consuming, but by using a non-invasive bladder assessment and biofeedback methods which reinforce the child's and family's understanding of bladder function, success can be achieved for some of the more difficult wetters. PMID- 11220840 TI - Comparing the use of ketamine and midazolam in emergency settings. PMID- 11220841 TI - Are nurses respecting and upholding the human rights of children and young people in their care? AB - Children's nurses may assume that the care they provide for children and their families is family centred and meets their holistic needs. However, very little objective evaluation has been undertaken with children and young people regarding the health services and nursing care they receive. In this study, data were collected from 18 young ventilator-dependent people and their families in order to evaluate their experiences of health and social care. The UN Convention and other policy documents advocating client-focused services were used as benchmarks for analysis, demonstrating that the needs and aspirations of the young people are not being addressed and raising questions for nurses and other professionals. PMID- 11220842 TI - Safe staffing levels for children's wards. PMID- 11220843 TI - Informed refusal is as important as informed consent. PMID- 11220844 TI - Family nursing: minimising discontinuity for hospitalised children and their families. PMID- 11220845 TI - Preparation for renal biopsy: a play package. PMID- 11220846 TI - Preparation therapy in A&E: a student reflection. PMID- 11220847 TI - The rise and fall of children's consent to surgery. PMID- 11220848 TI - President's message. A mission that's possible. PMID- 11220849 TI - After the flood. PMID- 11220850 TI - In the footsteps of Mary Breckinridge. A glorious 75th anniversary celebration. PMID- 11220851 TI - Reaching outside the box. An academic-community model to prepare nurses for the future. PMID- 11220852 TI - Creating an adolescent health promotion Internet.site. A community partnership between university nursing students and an inner-city high school. PMID- 11220853 TI - Introducing complementary/alternative strategies in a baccalaureate curriculum. PMID- 11220854 TI - A reflective teaching-learning process to enhance personal knowing. PMID- 11220855 TI - Clinical teaching strategies for a caring curriculum. PMID- 11220856 TI - What is an interim report? Why is it used? PMID- 11220857 TI - CHAP and the Department of Veterans Affairs. PMID- 11220858 TI - Paediatric coma scoring researched and benchmarked. PMID- 11220859 TI - Choking: a review of resuscitation protocols. PMID- 11220860 TI - Adolescent health care: the Irish experience. PMID- 11220861 TI - Jamie: living with cystinosis. PMID- 11220862 TI - Consent and the teenage Jehovah's Witness. PMID- 11220863 TI - Protecting children--a core skill. PMID- 11220864 TI - Visiting children in hospital: a vision from the past. PMID- 11220865 TI - Supporting learning in a specialist unit. PMID- 11220866 TI - Fever management in children. AB - Treating a child with a fever is a skilled nursing activity. This article explains the underlying physiological mechanisms of a fever and relates these to the clinical signs, symptoms and care of children. PMID- 11220867 TI - Child protection: why continuing education for nurses is important. PMID- 11220868 TI - [Thyroid status and clinical features of osteoarthrosis in the region of goiter endemia]. AB - AIM: The study of osteoarthrosis (OA) course in the region of goiter endemia regarding thyroid status. MATERIAL AND METHODS: The examination of 62 females with OA included enzyme immunoassay of blood TTH, T4, T3 and ultrasound investigation of the thyroid. RESULTS: OA patients were found to have subnormal levels of thyroid hormones and low thyroid index. Blood TTH rose with thyroid size. Joint changes were also directly related to thyroid size. CONCLUSION: Alterations in the thyroid status influence the course of degenerative-dystrophic process in the joints. PMID- 11220869 TI - [Nervous system changes in adrenal failure]. AB - AIM: To study nervous systems in chronic adrenal failure (CAF). MATERIAL AND METHODS: 262 patients with CAF were studied clinically, biochemically and electrophysiologically before and after treatment. RESULTS: The patients were found to have syndromes of vegetovascular dystonia by hypotonic type, syncopal paroxysms, myastenic, minor strokes, dyscirculatory-dysmetabolic encephalopathy, polyneuropathy. A direct correlation was established between the severity and duration of adrenal failure (AF), lowering of adrenal cortex hormones, coefficient Na/K and clinical manifestations of the neurological syndromes. Adequate hormone replacing and symptomatic therapy promoted a regress of neurological disorders in most of the patients especially in mild and moderate AF. CONCLUSION: Adequate therapy corrects neurological disturbances in patients with chronic NN. PMID- 11220870 TI - [Clinical effect and tolerance of paxil (paroxetine) in management of panic disorders]. AB - AIM: To determine clinical efficiency and tolerance of paxil (paroxetin) in the treatment of panic disorders. MATERIAL AND METHODS: An open, non-comparative 7 week study entered 60 patients (mean age 36.6 +/- 3.22 years) with panic disorders and agoraphobias with panic disorders. Paroxetin was given in a single daily dose 20-60 mg/day in the morning. The results were assessed by Hamilton and Sihan scales, scale of clinical impression, by reduction of panic attacks. RESULTS: In 72.2% of patients panic attacks ceased or occurred less frequently (by 50%). Anxiety relieved by 67 +/- 4.6%. The number of the responders was greater while the effect occurred faster in patients with panic disorders. The drug was well tolerated, side effects occurred in 43.3% of cases. They were mild or moderate. CONCLUSION: Paroxetin has a prominent anxiolytic and antiphobic action, is well tolerated and is effective in panic disorders and agoraphobia with panic disorders. PMID- 11220872 TI - [Mitral prolapse as a psychosomatic problem (review)]. PMID- 11220871 TI - [Role of grandaxin in the treatment of functional gastrointestinal diseases]. AB - AIM: To assess efficacy of grandaxine in correction of anxiety syndrome and vegetative dysfunction in patients with gastrointestinal diseases. MATERIAL AND METHODS: The trial included 59 patients with functional gastrointestinal, emotional and vegetative disorders who failed standard therapy. 43 patients of the test group received standard therapy in combination with grandaxine. RESULTS: Anxiety (Spilberg-Khanin scale), vegetative dysfunction (Vein scale) reduced in 90% of the patients of the test group more significantly than in the control group. Intestinal passage in patients with irritable colon syndrome improved also. CONCLUSION: A pronounced role of psychovegetative disorders was confirmed in development of functional gastrointestinal disorders. Grandaxine proved efficient in correction of such disorders irrespective of location of the pathology and prevalent tonicity of the autonomic nervous system. PMID- 11220873 TI - [Atopy and group of atopic and pseudo-atopic diseases. I. General understanding (lecture)]. PMID- 11220874 TI - [Allergic reactions to antibiotics (lecture)]. PMID- 11220875 TI - [Immunological indices in development of periodic disease]. AB - AIM: To specify immune changes in periodical disease (PD) in different periods of PD development as well as peculiarities of their changes in colchicin therapy. MATERIAL AND METHODS: Clinicoimmunological investigations including blast transformation of lymphocytes with lymphocytic mitogen and renal antigen, leukocyte migration inhibition with renal antigen, spontaneous and complementary rossette formation were made in 828 PD patients and 43 donors. RESULTS: Decreased functional activity and quantity of T-lymphocytes, their suppressory subpopulation was found in PD. The indices did not correlate with the disease variants and gender but with age and PD complication. In amyloidosis immunological indices deteriorate with positive trend after colchicin treatment. CONCLUSION: PD is characterized by strain in immunological process. PMID- 11220876 TI - [Viral hepatitis C and pregnancy]. AB - AIM: To evaluate course and outcomes of hepatitis C in gravidae; introduction of optimal management of pregnancy, postpartum period in mothers and newborns in viral hepatitis C. MATERIAL AND METHODS: Case histories, general and obstetric statuses, obstetric and extragenital pathology, pregnancy course and outcomes were studied in 76 pregnant women with viral hepatitis C. RESULTS: A complicated course of pregnancy was observed in 38.2, 13.1 and 24.3% of women in trimester I, II and III, respectively. Therapeutic policy of removing symptoms of the pathology with consideration of hepatitis C severity and stage allowed to keep pregnancy in all the women. CONCLUSION: Hepatitis C virus can complicate pregnancy but the latter does not aggrevate the course of hepatitis C. PMID- 11220877 TI - [Atenolol use in gestosis: clinical and hemodynamic aspects]. AB - AIM: To study clinical efficiency of atenolol in pregnancy hypertension with consideration of its cardiodynamic effects. MATERIAL AND METHODS: The trial included 36 women aged 19 to 41 years on pregnancy week 32 to 38. This study group had gestosis of the 1st and 2nd degree. Control group consisted of 14 healthy women with physiological pregnancy. All the examinees underwent atenolol test: measurement of heart rate, arterial pressure and ECG before, 30 and 90 min after introduction of a single atenolol dose 50 mg. Echo-CG was registered before and 90 min after administration of 50 mg amenolol, and on the treatment day 5. RESULTS: The response to atenolol in combined therapy of gestosis is the highest in gravidae with hyperkinetic type of circulation. CONCLUSION: Determination of the hemodynamic type is necessary for selection of antihypertensive drugs for treatment of gestosis. PMID- 11220878 TI - [New classification, diagnostic criteria and compensation of diabetes mellitus]. PMID- 11220879 TI - [Safety and clinical efficiency of long-term complete blockade of renin angiotensin-aldosterone system in patients with chronic obstructive pulmonary diseases]. AB - AIM: To study a corrective influence of a complete blockade of renin-angiotensin aldosterone system (RAAS) on right ventricular failure in patients with chronic obstructive pulmonary diseases (COPD). MATERIAL AND METHODS: 91 COPD patients were randomised into 3 groups who received standard therapy (ST), ST + losartan, ST + losartan + aldactone. The duration of the follow-up was 24 months. RESULTS: A complete RAAS blockade produced a significant decline in the pressure in the pulmonary artery, improved diastolic and systolic right ventricular function. This led to decreased number of hospitalizations because of progressing right ventricular failure. CONCLUSION: Safety of therapy with ACE inhibitor and aldactone was proved by a comparison of the number of side effects in the three groups. PMID- 11220880 TI - [Low back pain as a multidisciplinary problem (review)]. PMID- 11220881 TI - [Effect of vazaprostan on microcirculation in patients with scleroderma systematic]. AB - AIM: To investigate the effect of vazaprostan (alprostadil) on skin blood flow in patients with sclerodermia systematica (SS). MATERIAL AND METHODS: A total of 51 patients with SS aged 33-70 years were included in the study. 33 of them received a 3-hour infusion of vazaprostan at the standard dose for 20 consecutive days. The rest 18 patients received low molecular dextran solution. Before and at the end of the treatment digital skin microcirculation was measured with a laser Doppler flowmeter. The laser probe was attached to the distal pad of the ring finger on the left hand. Baseline blood flow and vascular reactivity in the tests with sympathetic stimulation, local heating and during orthostasis were evaluated. RESULTS: Baseline blood flow and vascular response to functional tests were significantly reduced in all the patients. At the end of the treatment the flow increased only in patients treated with vazaprostan. Vascular reactivity was not changed after the treatment in both groups of patients. CONCLUSION: Vazaprostan increases baseline blood flow and contributes to the improvement of microcirculation in patients with SS. PMID- 11220882 TI - [Morpho-functional condition of heart in patients with lymphogranulomatosis late after chemoradiotherapy]. AB - AIM: The study of clinical and echocardiographic status of the heart in patients with lymphogranulomatosis (LGM) late after chemoradiotherapy. MATERIAL AND METHODS: 44 patients with IIA-IV stage of LGM exposed to irradiation of lymph nodes and polychemotherapy according to the schemes ACOP, ABVD, COPP, CHOP, CVPP were examined. Echocardiography was carried out on the unit Sigma-44 and Toshiba. RESULTS: Some changes in the heart by type of myocardiodystrophy or endomyocardial fibrosis were found. The latter are characterized by diminution of the left and (or) right ventricles due to apex obliteration, hardening and thickening of the endocardium and subvalvular structures, diastolic dysfunction and pulmonary hypertension. The main and additional signs are distinguished. The reasons of endomyocardial fibrosis are discussed: severity of the disease, frequent exacerbations and, consequently, higher doses of specific chemoradiotherapy. CONCLUSION: It is necessary to employ sparing policy in planning radiotherapy after high loading antracycline antibiotics. PMID- 11220883 TI - [Skin symptoms in malignant hemopathies]. AB - AIM: To investigate specific and non-specific skin lesions in malignant hemopathies. MATERIAL AND METHODS: The study enrolled 862 patients (394 females and 468 males) with hematological malignancies treated in the hematological clinic from 1990 to 1998. The patients were divided into three groups according to the primary disorder: lymphoproliferative processes (541 patients), myeloproliferative processes (296 patients) and bone marrow hypoplasia (25 patients). RESULTS: The non-specific skin lesions showed high variability in morphology, location. Combinations of different lesions were also present. Specific lesions were less variable and more characteristic for lymphoproliferative processes. Skin lesions (specific or non-specific) were not found related to a particular disease. CONCLUSION: Skin lesions in oncohematological disorders appear in great variability. They are essential for diagnosis and may appear a single initial diagnostic marker in these conditions. PMID- 11220885 TI - [Some pathological aspects of viscera in parapsoriasis nodosus]. PMID- 11220884 TI - [Medicaments as ointments in combined treatment of osteoarthrosis]. PMID- 11220886 TI - [The ACE inhibitor spirapril in chronic renal failure, hypertension and diabetic nephropathy]. AB - The evidence from recent clinical outcome trials in arterial hypertension (AH) and the treatment guidelines from national and international authorities have placed a clear emphasis on "tight" blood pressure (BP) control. This has been particularly well illustrated in the treatment of patients with diabetes mellitus and AH where "tight" BP control clearly improves the outcome with reduced numbers of fatal and non-fatal cardiovascular events. Whilst the clinical trials in AH have identified benefits through BP reduction with a range of antihypertensive drugs there is a considerable volume of evidence to suggest that the optimal treatment for diabetic nephropathy and microalbuminuria should be based upon ACE inhibition. It is widely held that inhibition of intra-renal renin angiotensin systems leads to greater benefit than can be achieved by hemodynamic changes alone. Thus, management of AH and nephropathy in both DM and other forms of renal disease revolves around BP reduction through an ACE inhibitor-based treatment regimen. Where there is renal failure it may be prudent to administer a drug such as spirapril which has non-renal elimination mechanisms and which has been shown to have no accumulation problems or increased adverse effects. PMID- 11220887 TI - [Spirapril - a new long-acting ACE inhibitor: efficacy and safety in patients with arterial hypertension in combination with diabetes mellitus and impaired kidney function]. AB - AIM: To examine effectiveness and safety of quadropril. MATERIAL AND METHODS: Changes in blood pressure (BP), heart rate (HR), levels of glucose, potassium and creatinine, creatinine clearance were studied in 120 patients (48 males and 72 females, mean age 60.6 +/- 0.7 years) with mild to moderate arterial hypertension (AH) with average duration 13.8 +/- 0.7 years. The patients were divided into 3 groups: with AH (n = 40), AH + noninsulindependent diabetes mellitus (DM) (n = 43), AH and nephropathy (n = 37). 8-week treatment was performed with a standard dose of 6 mg/day (1 tablet of quadropril). Control examinations were made 2, 4 and 8 weeks after the treatment. RESULTS: After 8 weeks of treatment a decrease in systolic blood pressure in AH group was 24.0 +/- 3.0 mm Hg and in diastolic blood pressure 16.3 +/- 1.3 mm Hg (P < 0.001). In the group with DM this decrease was 22.4 +/- 2.8 mm Hg and 15.7 +/- 1.4 mm Hg (p < 0.001), respectively. In the group with nephropathy this decrease was 26.4 +/- 2.4 and 16.5 +/- 1.3 mm Hg (p < 0.001), respectively. Heart rate changed significantly only in diabetics: from 75.1 +/- 1.7 to 72.9 +/- 1.3 beats/min. Biochemical parameters in the hypertensive and diabetic patients did not change significantly. In the nephropathy group there was a significant decrease in creatinine and increase in creatinine clearance. Their level of glucose and potassium changed insignificantly. CONCLUSION: The treatment with quadropril results in a significant decrease in blood pressure, does not influence parameters of carbohydrate metabolism, improves nitrogen eliminating function of the kidneys. PMID- 11220889 TI - [Spirapril in patients with hypertension: clinical experience in Germany]. AB - AIM: To examine efficacy and tolerability of a single daily dose of 6 mg quadropril (spirapril). MATERIAL AND METHODS: An open multicenter study enrolled 5000 out-door patients with hypertension. All the patients received an ACE inhibitor quadropril for 3 months with four control visits (on week 0, 4, 8 and 12). RESULTS: Quadropril caused a marked decrease in systolic and diastolic blood pressure. At the end of the study 89.4% of patients had a systolic blood pressure reduction of at least 15 mm Hg and 85.4% had a diastolic blood pressure reduction of at least 10 mm Hg. There were no clinically significant heart rate changes. The overall tolerability of the drug was estimated as good or very good in 95.3% of patients. Only 2.9% of patients had side effects during treatment with once daily dose of 6 mg quadropril. No serious side effects were observed. CONCLUSION: 6 mg daily dose of quadropril is an effective and safe therapy for arterial hypertension. PMID- 11220888 TI - [Comparative study of spirapril (quadropril) and amlodipine efficacy. Results of randomized trial in patients with mild to moderate arterial hypertension]. AB - AIM: To compare in the non-blind randomised parallel study the efficiency of quadropril and amlodipine in the treatment of mild to moderate arterial hypertension. MATERIAL AND METHODS: A total of 80 patients (57.6 +/- 1.0 years) were included in this study. The patients were randomised in two groups, 40 patients each. Patients of group 1 received monotherapy with quadropril, while those of group 2 were treated with amlodipine. The treatment duration was 8 weeks in both groups. Quadropril was given in a fixed dose of 6 mg once daily. The initial dose of amlodipine was 5 mg/day. In case of insufficient effect the dose was elevated to 10 mg/day. The efficacy was evaluated by changes in blood pressure (BP) measured at rest. Moreover, in 50 randomly chosen patients 24-h monitoring of BP was performed at the start and end of the treatment. RESULTS: In the quadropril group baseline systolic BP reached 158.6 +/- 2.1 mm Hg, diastolic BP--101.8 +/- 0.8 mm Hg, heart rate was 74.3 +/- 1.6 beats/min. In the amlodipine group baseline systolic BP was 159.9 +/- 2.4 mm Hg, diastolic BP--101.8 +/- 1.0 mm Hg, heart rate was 71.3 +/- 1.0 beats/min. Systolic BP decreased at the end of quadropril therapy to 138.5 +/- 2.2 mm Hg, diastolic BP to 88.1 +/- 1.4 mm Hg. No significant change of the heart rate was observed. Under 5 mg of amlodipine systolic BP decreased to 137.9 +/- 2.5 mm Hg and diastolic BP to 87.1 +/- 1.6 mm Hg. Heart rate increased to 73.3 +/- 2.2 beats/min. Under therapy with 10 mg amlodipine systolic BP decreased to 145.9 +/- 3.8 mm Hg, diastolic BP to 89.7 +/- 3.4 mm Hg. Heart rate increased to 77.3 +/- 4.0 beats/min (p < 0.01). The hypotensive effect of quadropril remained stable while the effect of amlodipine decreased by the 8th week of therapy (p < 0.01). Side effects were observed significantly more often in the amlodipine group, then in the quadropril group. The main quadropril side effect was cough. Side effects observed in the amlodipine group were edemas, tachycardia, weakness. CONCLUSION: Both quadropril and amlodipine demonstrated a comparable antihypertensive effect although in 11 of 40 patients in the amlodipine group a dose increase was necessary and tolerability of quadropril was better. PMID- 11220890 TI - [Efficacy of quadropril (spirapril) vs capropril in treatment of essential hypertension]. AB - AIM: To compare the efficacy of monotherapy with quadropril (spirapril) vs captopril in essential hypertension. MATERIAL AND METHODS: 20 female patients aged 55 +/- 2 years with moderate hypertension (WHO classification) were included in the study. 16 patients had congestive heart failure stage II NYHA and 4 patients stage III NYHA. ECG and echocardiography were performed in all the patients. Two patient groups of 10 patients were treated for 6 weeks. Group 1 received 6 mg quadropril once daily. Group 2 received 25 mg captopril 3 times daily. The therapy was considered to be efficient if diastolic pressure (BP) was reduced to 90 +/- 5 mm Hg and systolic BP to 140 +/- 10 mm Hg from baseline values in the range of 210/120-170/100 mm Hg. RESULTS: The hypotensive effect of quadropril resulted in stabilisation of BP during the second week of therapy. A significant BP decrease was achieved at the end of 6 week therapy. Systolic BP fell from 178.8 +/- 3.2 to 145 +/- 5.6 mm Hd and diastolic BP from 109.7 +/- 1.2 to 92.4 +/- 1.7 mm Hg. Central and cardiac hemodynamic parameters improved. In one patient the condition improved from CHF stage III to stage II NYHA. No adverse effects were observed. A hypotensive effect of captopril reduced significantly systolic blood pressure from 182.1 +/- 2.7 to 150 +/- 4.6 mm Hg and diastolic BP from 110.4 +/- 1.1 to 100.1 +/- 1.9 mm Hg. Two patients developed adverse effects: cough and chest dyscomfort. CONCLUSION: Quadropril monotherapy showed to be more effective in diastolic BP decrease compared with captopril monotherapy and had advantages in one daily dose regimen, absence of the first dose effect and side effects. PMID- 11220891 TI - [Left ventricular myocardial hypertrophy in arterial hypertension: clinical significance, diagnosis, effects of antihypertensive drugs]. PMID- 11220892 TI - [The role of renin-angiotensin system in pathogenesis of pulmonary hypertension in patients with chronic obstructive pulmonary disease]. AB - Renin-angiotensin system (RAS) and hemodynamics in pulmonary artery (PA) were assessed in 25 patients with chronic non-obstructive bronchitis and 73 patients with chronic obstructive pulmonary diseases (COPD). RAS in COPD patients was activated. The degree of this activation rose with progression of respiratory failure. Hypertension in PA was secondary to RAS activation. The data were obtained on the essential role of RAS in the onset and progression of pulmonary hypertension. This allows to design new approaches to pathogenetic treatment of secondary pulmonary hypertension. PMID- 11220893 TI - [Poseidonol in the treatment of patients with hyperlipidemia]. AB - An antilipidemic effect of poseidonol was tested in 123 patients with ischemic heart disease, stable angina of effort (II-III functional class), 40 patients with secondary pyelonephritis and 40 patients with chronic hepatosis-hepatitis associated with chronic alcoholism or diabetes mellitus. The patients had also hyperlipidemia. A positive effect of poseidonol was established: cholesterol content fell by 25.4, 20.6 and 18.7%, respectively; triglycerides level decreased by 63, 42 and 21.4%, respectively; B-lipoproteins fell by 55.5, 36.9 and 13.1%, respectively. High density lipoproteins rose by 40.2, 27 and 69.9%, respectively. No adverse effects either on the liver or kidney functions were observed. PMID- 11220894 TI - [Psychopharmacotherapy and management of psychiatric care in somatic hospital]. AB - A clinical trial was made of 1994 patients admitted to a large general hospital in Moscow during a day in two seasons (spring, autumn). The aim of the study was to detect patients of a general hospital in need of psychotropic drugs, to assess their psychic condition and to develop recommendations for optimization of psychiatrist's consulting. It was found that 49.3% of the examinees need psychotropic drugs (at least one). 37.5% need tranquilizers, 20.7%--nootropic drugs, 21.2%--antidepressants, 5.9%--neuroleptics. PMID- 11220895 TI - [Multiple endocrine neoplasia of the first type (Wermer's syndrome)]. AB - 11 patients with Wermer's syndrome (WS) aged 24-67 years were treated. They had a total of 30 tumors: 4(13.3%) hypophyseal, 11(36.7%) pancreatic, 9(30%) parathyroid, 4(13.3%) adrenal and 2(6.7%) duodenal. Each patient had two tumors minimum and 8 tumors maximum. In 8 cases WS presented clinically as hypoglycemia, in 3 cases as Zollinger-Ellison syndrome. The diagnosis was made using ultrasonography, CT, MRT and angiography. Cytogenetic examination was made in 2 cases. All the patients were operated. Six of them were operated two times, one- four times. The following surgery was made: 4 removals of parathyroid adenomas, 4 adrenalectomies, 1 removal of the hypophysis, 4 enucleations of pancreatic insulinomas, 5 distal hemipancreatectomies, 1 distal subtotal resection of the pancreas, 1 gastropancreatoduodenal resection. Clinically symptomatic tumors should be operated first. PMID- 11220896 TI - [Local cellular and humoral immunity in pneumonia patients]. AB - The paper reports a study of some local immunity factors in pneumonia aimed at specification of mechanisms inducing respiratory immunodeficiency and their effects on the disease course. Local cellular immunity of the lungs was studied by estimation of the total number of cells in the bronchoalveolar lavage, their viability, alveolar macrophages (AM), neutrophils, T- and B-lymphocytes, AM and neutrophil phagocytic index and number, receptor apparatus. The lavage IgA, IgM, IgG, lysozyme were estimated. It was found that local cellular and humoral immunity depend on clinicoetiological form of pneumonia. Cellular and humoral immunodeficiency was the greatest in staphylococcal infection. The role of cellular and humoral immunity dysfunction in the lungs in genesis of bronchoobstructive syndrome is specified. Recovery of cellular and humoral immunity in pneumonia reconvalescents is behind clinical recovery. Grave immunodeficiency in severe or lingering pneumonia may be a pathogenetic factor of chronic inflammation in the lungs. To evaluate functional condition of local immunity of the lungs it is valid to study cellular and humoral factors of local pulmonary immunity in bronchoalveolar lavage. PMID- 11220897 TI - [Effects of antihypertensive drugs with different mechanism of action on cardiac hemodynamics in patients with artificial pacemaker]. AB - Cardiohemodynamic effects of obsidan, nifedipin, captopril and prasosine were compared when the drugs were given in a 4-week course regarding circulation type and stimulation regime to 74 patients with artificial pacemaker suffering from mild or moderate essential hypertension. A peculiar action of obsidan, nifedipin and prasosine in cardiac pacing found at echocardiography is explained by the absence of frequency-dependent (chronotropic) cardiohemodynamic effects. Obsidan lowered blood pressure most effectively in hyperkinetic circulation. Nifedipine, captopril and prasosine were more potent in eu- and hypokinetic circulation. Reduction of arterial pressure by the above peripheral vasodilators in patients with hyperkinetic circulation results from a fall of total peripheral vascular resistance initially elevated by 16.5%, on the average. In isolated ventricular stimulation (regime VVI) vs atrial one (AAI regime) hypotensive action of the above drugs was more potent, but side effects were more frequent. PMID- 11220898 TI - [Mineral corticism syndrome: classification, etiology and pathogenesis]. PMID- 11220899 TI - [Renitec and ednit in the treatment of cardiac failure associated with duodenal ulcer]. AB - The influence of renitec and ednit on duodenal ulcer was studied in 25 patients with cardiac failure. It was found that renitec and ednit lowered both systolic and diastolic pressure, relieved gastralgia and dyspepsia. Duodenal ulcer healed in 87% of the patients. Contracting and pump function of the right ventricle improved. Plasma levels of angiotensin and aldosteron decreased while prostaglandin E2 increased. PMID- 11220900 TI - [Treatment of irritable bowel syndrome with dicetelium and spasmomen]. AB - The aim of the study was to compare clinical efficacy of new spasmolytics- pinaverium bromide (dicetel, Solvay Pharma) and otilonium bromide (spasmomen, Menarini-Berlin-Chemie)--in the treatment of irritable bowel syndrome. Effects appearing during the treatment with anxiolytic drug tofisopam (grandaxin, Egis) after using dicetel and spasmomen were also studied. The results indicate marked clinical efficiency of dicetel and spasmomen which improve vegetative functions and psychoemotional status. Grandaxin provides further improvement of clinical symptoms and additionally corrects psychoemotional status. PMID- 11220901 TI - [Fliformine effects on blood lipid spectrum and lipid peroxidation in obese patients]. AB - Blood lipid spectrum and lipid peroxidation are compared in patients with different obesity types. Diet treatment is compared to biguanides derivatives (gliformine) in patients with body obesity combined with dislipidemia. Gliformine proved more effective in correction of changed lipid spectrum of atherogenic origin, improves lipid peroxidation. Biguanides seem perspective in management of lipid disbolism in patients with body obesity. PMID- 11220902 TI - [Respiratory distress syndrome in patients with sepsis]. PMID- 11220903 TI - [Information necessary for a doctor using a computer]. PMID- 11220904 TI - [Primary antiphospolipid syndrome causing thrombosis of hepatic vein]. PMID- 11220906 TI - [Gastroesophageal reflux disease and Helicobacter pylori]. PMID- 11220905 TI - [Effectiveness of thrombolysis and balloon angioplasty in a patient with a combined infarction of the left and right cardiac ventricle]. PMID- 11220907 TI - [Hyponatremia syndrome in patients with chronic cardiac failure]. PMID- 11220908 TI - [History of the idea of staged clinical education. Communication. 1. Events of 1835-1840]. PMID- 11220909 TI - [Spectro-fluorescence analysis of ALA-induced protoporphyrin IX in differential diagnosis of stomach disease]. AB - The results of examination of 47 patients with confirmed diagnosis of cancer of the stomach (21 patients) or 26 suspects were analyzed. 2-4 hours after oral taking of Alasence in the dose 5-10 mg/kg, gastroscopy with spectrofluorescence analysis of ALA-induced protoporphyrin IX was performed. There were no toxic complications due to Alasence taking. The standard spectrodetector LESA-7 was used for fluorescence record registration. The fluorescence spectra were recorded in the range of 650-850 nm. The specific for protoporphyrin IX peak at 700 nm wavelength was analyzed. Fluorescent endoscopic diagnosis allowed to confirm stomach cancer in 21 patients, and to detect cancer in 7 patients, including 2 cases of cancer in situ. The contrast of protoporphyrin IX accumulation (tumor/norm ratio) ranged from 2.5 to 18, that was enough for differential diagnosis in the majority of cases. In analysis of spectrograms for correct contrast calculation it is necessary to take into account the own fluorescence, with was high in some cases. PMID- 11220910 TI - [Choice of surgical treatment method for peptic ulcer of operated stomach]. AB - The analysis of immediate and long-term results of surgical treatment in 98 patients with peptic ulcer of operated stomach is presented. The choice of surgical method was determined by the disease cause. Reconstructive stomach resection by Bilrot-II in Roux modification was operation of choice in peptic ulcer with non-hormonal factors of ulcerogenesis. When hormonal cause of ulcerogenesis was suspected, even in unknown origin of hypergastrinemia, the extirpation of gastric stump is indicated. Trunkal vagotomy can be performed as an additional surgical method only. Favorable surgical outcomes were seen in 90 (91.8%) patients. Long-term results from 2 to 15 years were studied in 74 (82.2%) patients. They were recognized as good in 48 (53.3%) patients, as satisfactory- in 12 (13.3%). The recurrence of the disease was seen in 4 (4.4%) patients. 10 patients died due to causes not associated with stomach diseases. PMID- 11220911 TI - [Differential diagnosis of pancreatic head cancer]. AB - The results of clinical, instrumental and laboratory examinations were analyzed for 99 patients. 59 of them had pancreatic head cancer, 40--chronic pseudotumorous pancreatitis. The importance of complex ultrasonic diagnosis in detection of pancreatic diseases (98%), in true diagnosis of unresectable tumors (96.7%), and also in determination of bile ducts lesion level in obstructive jaundice is shown. It was revealed that spiral computed tomography (SCT) had an advantage over computed tomography in diagnosis of pancreatic tumors and in assessment of their resectability. Sensitivity of combined use of US, SCT and tumor marker CA 19-9 in pancreatic cancer diagnosis increases to 95.2%. High diagnostic value of laparoscopy with laparoscopic ultrasonic examination as a method of final assessment of tumor resectability is shown. PMID- 11220912 TI - [Experience of laparoscopic cholecystectomy in calculous cholecystitis]. AB - Laparoscopic cholecystectomy (LCE) was performed in 330 patients aged from 14 to 77 years; it was completed successfully in 308 (93.3%) patients. Conversion to laparotomy and standard cholecystectomy was carried out in 22 patients (6.7%) due chiefly (86.4%) to inflammatory disorders of infrahepatic area. 188 (61%) LCE were performed for chronic calculous cholecystitis, 120--for acute calculous cholecystitis. In the latter group destructive forms of cholecystitis were revealed in 34.2% patients. Combined with LCE interventions were performed in 13 patients (4.2%). There were no lethal outcomes after LCE. Severe intra- and postoperative complications occurred in 26 (8.4%) patients; laparotomy for removing these complications was necessary in 3 patients (1%). PMID- 11220913 TI - [Correction of lymph circulation in liver cirrhosis]. AB - The approach to surgical correction of lymph circulation in hepatic cirrhosis is described. The main criteria in the choice of operations draining neck lymphatic duct were hyperkinetic central hemodynamics with high functional pressure in thoracic lymphatic duct and lymphovenous pressure gradient, central or mixed type of intrahepatic lymph flow. All the 26 patients underwent transvenous external internal drainage of thoracic duct as a temporal measure for stabilization of patients state. Reinfusion of lymph after lymphosorption promoted detoxication in hepatic failure in patients with cirrhosis, complicated by resistant ascites. Low pressure indices of central lymphodynamics and mixed intrahepatic lymph flow are indications for anastomosis creation between right lumbar vein and right lymphatic duct. In this case it is possible to save the behind-hepatic portion of cava inferior in potential recipients of liver transplants. PMID- 11220914 TI - [Laparoscopic treatment of hydatid liver cysts]. AB - Laparoscopic hepatic hydatidectomy (LHE) was performed in 37 patients. Conversion to laparotomy in one case was caused by intrahepatic location of liver cyst. In 36 patients after LHE, the postoperative period was significantly easier than after standard operation. There were the following complications: bile efflux in abdominal cavity (1), bile efflux from residual cavity (2), suppuration of residual cavity (1). The complications were removed without laparotomy, all the patients recovered. The patients were discharged on day 5.6 on the average. LHE is a promising method of surgical treatment for uncomplicated liver echinococcosis. PMID- 11220916 TI - [Thermal trauma in a combination with respiratory tract burn]. AB - The detection rate of microbial contamination of burn wounds after flame burn was studied in dynamics to 3 weeks in 56 patients forming 2 similar groups: basic- with thermo-inhalation lesions (TIL) and control--without TIL. General area of skin burns in all the patients was less than 50% of the body surface, on average it was 40%, the area of deep burns was 23%. Cytological and bacteriologic methods were used for study microphlora in the sputum and in bronchoalveolar lavage. There were 186 cases of wound microbial contamination (gram-negative microorganisms--64.4% cases, gram-positive--34%, pathogenic fungi--1.6%). In 80% cases the microphlora of the wounds was polymicrobial, in 47% cases the microphlora were detected on the second week. Microphlora was detected 2 times more often in the basic group than in the control, corresponded to skin burn area; the greatest exceeding of critical level of wound contamination was revealed on the first 2 weeks. In TIL besides wound contamination, polymicrobial microphlora revealed in tracheobronchial tree, presented on the first 2 weeks with association of gram-positive and gram-negative microorganisms, combining on week 3 with fungal phlora. Early leukocytosis, not reducing during first 3 weeks of the study, due to intoxication by burn products, occurred in TIL. Early lymphopenia in TIL was the sign of resistant immunodeficiency. PMID- 11220915 TI - [Use of CO2-laser in the treatment of liver hydatid echinococcosis]. AB - The results of laser scalpel use in 226 patients with hepatic echinococcosis are analyzed. Laser beam produces coagulation of the small vessels and intrahepatic bile ducts, destroys alive protoscolexes, suppresses microphlora. It ensures easier postoperative period, reduces postoperative complications rate 4 times, hospital stay 2 times. PMID- 11220917 TI - [Treatment of heart wounds]. AB - Care results in 48 patients (male--38, female--10) with heart wounds (HW) were analyzed. 40 (83.2%) patients had stab-incised wounds, 7 (14.7%)--stab wounds, 1 (2.1%)--gunshot wounds. 23 (47.8%) patients were hospitalized in consciousness, 17 (35.3%)--in unconsciousness, 8 (16.9%)--in twilight state. The lethality among the latter two groups of the patients was 64%, in the former group--13%. 19 patients from 48 died: in preoperative period--3, during operation--10, in early postoperative period (more than 10 days)--2 patients. The suspected of HW patients must be transported in the nearest surgical hospital. In unstable hemodynamics it is necessary to carry out adequate infusion therapy, in obvious signs of heart tamponade the pericardium puncture must be performed. In agonizing patients, and in case of general anesthesia delay, it is necessary to begin thoracotomy before general anesthesia. PMID- 11220918 TI - [Lumbar sympathectomy in atherosclerosis obliterance of lower limb arteries and age of the patients]. AB - In the elderly and old patients with atherosclerosis of lower limb arteries, ultrasonic dopplerography assisted study of hemodynamics in foot with use of Valsalva and corinfar tests was carried out. It is revealed that these patients retain high reaction to sympathetic influences. The obtained data were the base for use of lumbar sympathectomy in 419 patients over 65 years as an independent method of surgical treatment and in combination with reconstructive operations on major arteries. Good results were obtained in 70.1% operated patients, satisfactory results--in 22.7%. There were no significant differences in the results of lumbar sympathectomy between this age group and younger patients. PMID- 11220919 TI - [Health care standards for surgical patients in clinical hospital]. AB - In Russian Federation the Obligatory Health Insurance Standards are based on the a priori expert assessments but not on statistical analysis of really recorded cases. This leads to the essential standard incompleteness, indistinctness and heterogeneity. In Vishnevsky Institute of surgery the "Automatized system for care registration in hospital" was designed, and data base on more than 10,000 patients treated in 1995 to 1999 was created giving now the starting-point for further efforts for overcoming the above standards insufficiency. PMID- 11220920 TI - [Posterior mediastinal esophagoplasty with by operated stomach in a patient with single lung]. PMID- 11220921 TI - [Tuberculous omentitis]. PMID- 11220922 TI - [Aneurysm of pancreatoduodenal artery associated with celiac trunk occlusion]. PMID- 11220923 TI - [Risk evaluation of extracardiac operation in patients with concomitant cardiovascular diseases (review)]. PMID- 11220924 TI - [Surgery in Ancient Rome]. PMID- 11220925 TI - [Experimental, morphological and clinical aspects of transmyocardial laser revascularization]. AB - Experimental, pathomorphological and clinical data substantiating use of transmyocardial laser revascularisation in the treatment of coronary heart disease (CHD) are presented. It is shown that the objective criterion of clinical efficacy of transmyocardial laser revascularisation in 58 patients with CHD is an increase of myocardial perfusion due to neoangiogenesis. This leads to improvement of cardiac function and general state of the patients. Surgical intervention has no substantial influence on contractile function of left ventricular myocardium in patients with CHD. PMID- 11220926 TI - [Clinical experience with low- and minimal-flow isoflurane in extensive resections of the liver and liver transplantation]. AB - A comparative study was performed of general balanced anesthesia on the basis of neuroleptic analgesia (NLA) and inhalation low- and minimal-flow anesthesia with isoflurane in anesthesiological management of extensive operations on the liver. A total of 75 anesthesias were conducted. Because of low hepatotoxicity, absence of its metabolites' pharmacological activity, fast elimination from the body unchanged, isoflurane is effective in long and traumatic operations on the liver. Low-flow isoflurane significantly lowers pharmacological load with opiates, myorelaxants which is essential in patients with hepatic diseases. This leads to more rapid recovery of adequate spontaneous respiration and activation of the patient in low risk of postoperative iatrogenic complications. PMID- 11220927 TI - [Anesthesia, changes in hemodynamics and metabolism in surgical treatment of thoracic and abdominal aortic aneurysms]. AB - 45 patients aged 32-63 years operated on for dissecting aneurysm of the thoracoabdominal part of the aorta were divided into 2 groups. Group 1 patients (n = 36) were operated on with application of the bypass using centrifuge pump. Group 2 patients (n = 9) were operated on without the bypass. The results evidence that the employed anesthesia and infusion therapy in combination with the bypass maintained by the pump provide stable intraoperative hemodynamics and prevent renal failure. Usage of the bypass in combination with liquor drainage reliably protects spinal cord from ischemia, especially in patients with long term aortic ligature. PMID- 11220928 TI - [Functional state of the right and left heart at different stages of anesthesia in patients with ischemic heart disease during myocardial revascularization surgery]. AB - 57 ischemic heart disease (IHD) patients entered the study of right and left heart function at different stages of anesthesia and operation to reveal possible reasons of myocardial dysfunction and to propose effective prevention of this dysfunction. All the patients were operated on under multicomponent balanced anesthesia (relanium, fentanyl, arduan, nitric oxide with oxygen 1:1). Left ventricular function was assessed at Doppler echocardiography, right ventricular function--at catheterization of the lung artery with a Swan-Ganz catheter with low time constant. Hemodynamic monitoring was made with a domestic MX-04 monitor. It was found that in the preperfusion period diastolic function of the right and left ventricles is impaired much more than the systolic one. The conditions of anesthesia and operation affect right ventricular function more than the left one. Diastolic and systolic right ventricular dysfunctions were observed at all stages and three stages of the operation, respectively. Diastolic and systolic left ventricular dysfunction was observed at four and one stages, respectively. Basic causes of the above systolic and diastolic disorders in the preperfusion period may be tachycardia, arterial hypertension, reduction of the preloading and increased postloading (for the right ventricle) in artificial lung ventilation. PMID- 11220929 TI - [Epidemiology and prevention of anaphylactoid reactions in heart surgery patients]. AB - A retrospective analysis of the incidence, severity, and causes of anaphylactoid reactions (AR) in 1504 cardiosurgical patients operated on at Research Center of Surgery in 1995-1999 showed that AR occurred in 109 (7.4%) patients: 60% during aortocoronary bypass operations, 27.2% during correction of acquired heart diseases, and 12.8% during correction of congenital heart diseases. Skin symptoms predominated in the structure of AR (59.7%); cardiovascular episodes ranked second (38.5%), and the incidence of pulmonary reactions was lowest (1.8%). The causes of AR during anesthesia and surgery were platelet-rich plasma and fresh frozen plasma (35.3%), antibiotics (12.1%), protamine (12.1%), myorelaxants (9.9%), colloid plasma substitutes (8.8%), dioxidine (3.3%), heparin (2.2%), aprotinin (1.1%), diazepam (2.2%), and other agents (7.6%). A history of AR and repeated interventions are risk factors of AR. The protocol of AR prevention in cardiosurgical patients includes determination of risk factors, selection of the least hazardous agents, strict adherence to the rate of infusion of histamine releasing drugs, minimum utilization of donor blood components (platelets and plasma), use of H1 and H2 blockers, corticosteroids (celestone) during premedication and operation. Such treatment helped decrease the severity and incidence of AR in cardiosurgical patients to 4.7%. PMID- 11220930 TI - [Anesthetic management of the surgical correction of heart valve defects combined with myocardial revascularization]. AB - Thermodilution volumetry of the right ventricle (RV) in the course of combined operations has demonstrated significance of RV function and identified signs of its dysfunction when other parameters of hemodynamic monitoring were low informative. Of late, introduction of updated anesthetic modalities and intraoperative monitoring have noticeably improved surgical outcomes of combined lesions of the heart as shown by decreased hospital lethality. PMID- 11220931 TI - [Use of clofelin in the prevention of perioperative myocardial dysfunction in patients with ischemic heart disease]. AB - The purpose of this study was to evaluate the possibility of using clofeline in anesthesiological protocol for myocardial revascularization as a drug preventing hemodynamic disorders and perioperative myocardial dysfunction. In group 1 (27 pts.) clofelin was used in premedication (150 micrograms at night on the eve of surgery and before the operation), group 2 (29 pts.) was control. Clofelin improved the stability of the cardiovascular system, decreased the incidence of hyperdynamic reactions, episodes of myocardial ischemia, and cardiac arrhythmia during surgery. Use of clofelin for premedication decreased the need in inotropic support during the postperfusion period from 49 to 37% and ensured a higher cardiac production during transfer from artificial to spontaneous circulation. PMID- 11220932 TI - [Autonomic reactivity and intraoperative arterial hypertension in patients with ischemic heart disease]. AB - As patients with ischemic heart disease (IHD) may develop intraoperative hypertensive and hyperdynamic reactions provoking myocardial ischemia, the authors estimated reactivity of the autonomic nervous system before giving anesthesia. This was made for prediction of intraoperative hypertensive reactions and choice of an optimal anesthesia variant. Combination of spectral analysis of variability of the heart rhythm and active orthostatic test was employed for this purpose in 50 IHD patients undergoing myocardial revascularization. PMID- 11220934 TI - [Human factor in anesthesiology]. AB - The authors analyze the role of "human factor" in anesthesiology as a combination of characteristics which can influence the efficiency of physician's work. Anesthesiologists should possess professional skills directly concerned with mental adaptation of personality responsible for decision making in stress or emergency. Examination of 37 anesthesiologists who had given their informed consent helped determine the psychodiagnostic criteria of professional skills and gave grounds for forming groups liable to maladaptation under high psychoemotional strain. Relationships between age, sex and professional activity were assessed. It is recommended to introduce a system of professional selection of candidates wishing to become an anesthesiologist, of individual approach to optimization of the work intensity for practicing anesthesiologists. Psychological relaxation for anesthesiologists is also essential. PMID- 11220933 TI - [Prevention of negative hemodynamic effects of protamine sulfate by simultaneous infusion of microdoses of adrenaline]. AB - Two groups of coronary patients subjected to revascularization of the myocardium were examined in order to detect the negative hemodynamic effects of protamine sulfate (PS) and the possibility of their correction by simultaneous infusion of adrenaline microdoses. In group 1 (27 pts.) heparin was neutralized by infusion of PS alone (6 mg/kg) and in group 2 (27 pts.) by simultaneous infusion of PS and adrenaline (15 ng/kg/min). The functions of the right and left ventricles were evaluated by catheterization of the pulmonary artery by a Swan-Ganz catheter and transesophageal Doppler echocardiography. These methods provided volume and velocity characteristics of the right and left compartments of the heart. PS deteriorated the systolic function of the right ventricle, particularly in patients with initial dysfunction of the right heart. Infusion of adrenaline simultaneously with PS leveled its negative effects, thus preventing myocardial dysfunction. PMID- 11220935 TI - [Results of the treatment of cardiac surgery patients with postoperative acute respiratory distress syndrome by prone-position pulmonary ventilation]. AB - Prone position ventilation (PPV) became an effective method of management of ARDS since 1974. Its positive effects on arterial oxygenation have been amply described, but its impact on the results of treatment and hospital mortality remains a disputable point. We observed 2 groups of patients, 36 pts. each, with ARDS after cardiovascular surgery. The main causes of ARDS were shock syndrome, massive blood loss and transfusion, previous COPD, and postcardiopulmonary bypass ALI. Because of impaired lung function (PaO2/FiO2 < 200), all patients were supported by special methods of ventilation including PEEP, high FiO2, and PCV with inverse I:E ratio. In the main group, PPV was started on days 3.6 +/- 1.2 postoperation. Daily duration of PPV was 4-12 h, after which the patients were turned into a supine position. Controls were treated in a supine position. The groups were identical by age, sex, types of surgery, severity of ARF, and manifestations of MOSF. PPV improved lung function and arterial oxygenation. Clinical outcomes were better in the PPV group than in the controls: a lower frequency of threatening arrhythmia, better results of MOSF treatment, and lower mortality (69 and 33.4%, respectively). Prone position is an effective measure improving arterial oxygenation in patients with ARDS after cardiovascular surgery. The main results of PPV are decrease in complications induced by hypoxia and higher survival rate. PMID- 11220937 TI - [Analysis of complications and the problem of airtightness of the respiratory contour during the use of laryngeal masks in children]. AB - Feasibility of adequate gas exchange in artificial lung ventilation (ALV) through laryngeal mask (LM) is investigated in view of high occurrence of leakage of the respiratory contour. Adequate anesthesiological techniques of LM usage are proposed. It is shown that airtightness at the site of LM cuff contact with the upper larynx is not complete. The magnitude of respiratory mixture loss in audible leakage permissible for adequate ventilation and gas exchange is estimated. PMID- 11220936 TI - [Correction of secondary immunodeficiency as a method of prevention of suppurative-septic complications after surgery with artificial blood circulation]. AB - Eighty-five patients with acquired heart diseases with and without infective endocarditis (IE) were examined. In one group of patients traditional therapy was supplemented by the Russian drug immunofan, a synthetic hexapeptide with immunomodulating, antiinflammatory, and detoxifying effects. A course consisted of 10 intramuscular injections every other day (1 ml of 0.005% solution). The drug was prescribed after immunological studies on a laser flow cytometer (Becton Dickinson, USA). Correction was carried out before and after the operation. The postoperative period was uneventful in patients treated with immunofan; the incidence of clinical manifestations of IE was decreased. The concentrations of cytokines (IL-1, IL-6, TNF-alpha) in the blood were increased in patients with IE. In patients treated with immunofan, the concentrations of cytokines were decreased and immune parameters were normalized. Changes in the cytokine status can be used as a laboratory test for evaluating the efficiency of treatment in cardiosurgical patients with IE. PMID- 11220938 TI - [Use of new respiratory technologies in solving problems of artificial one-lung ventilation in thoracic surgery in high-risk patients]. AB - The authors proposed a separate independent (or differentiated) artificial lung ventilation as an appropriate alternative variant of artificial lung ventilation (ALV). This approach implies bulky ALV of the operated lung and high-frequency ventilation of the contralateral lung. In patients with associated respiratory diseases and stage II-III respiratory insufficiency, ALV initiates high pulmonary hypertension, intrapulmonary bypass of 50% cardiac output. The differentiated ALV on principal operation stage optimizes homeostatic parameters vs both one-lung and conventional ALV. For patients with stage II-III respiratory insufficiency and cardiovascular disease ALV is contraindicated. Differentiated ALV is the only alternative allowing surgical treatment of lung diseases in high risk patients. PMID- 11220940 TI - [Introduction and development of artificial circulation at the Russian Research Center of Surgery RAMN]. PMID- 11220939 TI - [Prevention of hemodynamic disorders during anesthesia in middle-aged and elderly patients with essential hypertension. Components of anesthesia. II]. AB - Hemodynamic parameters were evaluated during various stages of anesthesia in two groups of patients aged 60-85 years with mild essential hypertension. In group 1, routine preoperative treatment with hypotensive drugs was carried out and in group 2 differentiated preoperative treatment with calcium antagonists was carried out with consideration for a hemodynamic type. Group I patients were operated on under traditional neuroleptic analgesia (NLA), group 2 under NLA with 40% lower drug doses than in group 1 and with addition of calcium antagonists. To patients with hypo- and eukinetic hemodynamics, nifedipine was injected (bolus injection) in a dose of 14.2 micrograms/kg before induction and then was infused in a dose of 6.0-14.2 micrograms/kg/min. Patients with hyperkinetic hemodynamics were injected verapamil in a dose of 70-140 micrograms/kg (bolus injection) and then the same dose every hour of the operation. Differentiated use of calcium antagonists during anesthesia helped transform the hyper- and hypokinetic types of hemodynamics into a more rational eukinetic type, which was associated with a decrease of MVO2. Calcium antagonists, exerting analgesic, automatic stabilizing, and antihypoxic effects, prevented the hyperdynamic reactions complicating NLA in 30% cases and precluded complications of concomitant ischemic diseases, which were observed in 40% of group 1 patients. PMID- 11220942 TI - [Perfusion management in liver transplantation]. AB - Veno-venous bypass (VVB) with a Biopump centrifugal pump (Biomedicus, USA) was used in 36 patients with liver diseases during orthotopic transplantation of the liver. Volume rate of perfusion (VR), systolic, diastolic, and mean arterial pressure (AP), and central venous pressure (CVP) were monitored. VR during liver free period was 850-1350 (1064.2 +/- 87.5) ml/min in femoral-axillary bypass and 1700-3500 (2630.5 +/- 112.3) ml/min in femoral-porto-axillary bypass. A trend to a decrease of the mean AP to 65 mm Hg was observed at the end of liver-free period (p < 0.05), while CVP decreased to 2 mm Hg (p < 0.05); there was a trend to a moderate tachycardia. No significant shifts in acid-base balance, oxygen balance, and blood electrolytes were observed during the liver-free period. Maximum blood loss occurred during the liver-free period and reperfusion of the transplant. Blood loss was evaluated by the amount of washed autoerythrocytes obtained after processing of collected blood in the Cell-Saver device. VVB had a favorable impact on the course of orthotopic transplantation of the liver, maintaining stable hemodynamic and biochemical parameters and preventing ischemia of the abdominal organs. Preservation of autoerythrocytes by the Cell-Saver device minimized the need in donor erythrocytes, thus ruling out the complications associated with homologous blood transfusion. PMID- 11220941 TI - [Causes of myoglobinemia in surgery with artificial circulation]. AB - Release of myoglobin (Mg) into the plasma and increase of its concentration during perfusion are a result of muscle cell injury during artificial circulation. High values of oxygen tension and hypothermia during cardiosurgery are sources of active oxygen forms damaging the biomembranes. We investigated release of Mg into the blood and relationship of this parameter with oxygen tension and depth of cooling. 95 patients were tested during open-heart surgery and operations on the main vessels: 25 perfusions at 30-32 degrees C, 41 at 26-29 degrees C, and 20 at 12-14 degrees C. The patients were divided into subgroups depending on arterial blood oxygen pressure. Myoglobin release into the blood was minimum under mild hypothermia and moderate PaO2. The degree of myoglobinemia increased with elevation in PaO2. As body temperature decreased, the concentration of Mg increased and differences between the groups with different PaO2 leveled. Critical myoglobinemia (30-fold vs. the initial value) was observed in the group with the deepest hypothermia (14 degrees C). Since the myocardium contains high amounts of Mg, it is clear that loss of this heme-containing protein impairs the feeding of the myocardium and, hence, decreases its contractility. PMID- 11220943 TI - [Anesthesiologist and chronic pain]. AB - Effective therapy of chronic frequently recurring pain is a complex important problem from practical medical, social, and economic viewpoints. Organization of specialized "pain clinics" and pain control centers is discussed. These institutions will take care of patients with chronic pain syndromes. The role of anesthesiologists and reanimatologists at such clinics is analyzed. Experience gained at department of therapy of painful syndromes at the Russian Center of Surgery of the Russian Academy of Medical Sciences and the Integrative Medicine Center attached to it is reviewed. The authors offer recommendations on the use of traditional and nontraditional methods of pain relief. New highly effective integrative diagnostic methods (computer pulsometry) and therapies (resonance electropuncture analgesia and therapy) are used in various pain syndromes, including chronic frequently relapsing, which are usually resistant to common methods. Integrative methods of clinical reflex therapy create conditions for replacing traumatic surgical and radiological methods used in the treatment of critically ill patients by methods of integrative medicine. PMID- 11220944 TI - [Prevention of postoperative pain: pathogenetic bases and clinical aspects]. AB - The trial aimed at development of pathogenetically sound complex of therapeutic measures to prevent postoperative pain or relieve it significantly included 1912 patients after elective surgical interventions on the lower part of the body. It is shown that basic factors in postoperative pain prevention are the following: a) adequate relief of preoperative pain syndrome; b) use of spinal or spinal epidural anesthesia as the leading anesthesia method; c) preoperative epidural administration of opioid analgetic drugs; d) pre-, intra- and postoperative administrations of drugs affecting N-methyl-D-aspartate-receptors (ketamine, magnesium sulphate) as well as inhibitors of kininogenesis and prostaglandinogenesis. The success lies in a multimodality approach to prevention of postoperative pain syndrome, i.e. maximal eradication of all the factors promoting onset of pain during pre-, intra- and postoperative period with a simultaneous impact on peripheral and central mechanisms of acute pain. Such an approach resulted in a complete prevention of postoperative pain in 46.2% patients while the rest patients had much less intensive pain. PMID- 11220945 TI - [Continuous epidural infusion of ropivacaine in the postoperative period]. PMID- 11220946 TI - [Use of laryngeal masks: variants of hemodynamic response to various methods of anesthesia]. AB - Choice of induction agent is the decisive factor in utilization of a laryngeal mask (LM) under spontaneous respiration, as insufficient relaxation and unwanted laryngopharyngeal reflexes deteriorate the efficiency of LM functioning during operation and anesthesia. 132 anesthesias with LM were performed, 86 of these for laparoscopic cholecystectomies (LCE) (group 1) and 42 for saphenectomies (group 2). Control group consisted of 60 patients anesthetized for LCE by means of an endotracheal tube (ETT). Combined induction intravenous anesthesia with ketamine, barbiturates, and diprivan was used in group 1 and controls. In group 2 induction anesthesia was based on ketamine and diprivan. Group 1 and control group were matched for demographic characteristics and concomitant diseases. All groups were divided into subgroups, depending on anesthesia. In all groups pipecuronium bromide (0.06 mg/kg) was administered before insertion of EET or LM after injection of induction agents. In total myoplegia, installation of LM was simple, involving no untoward laryngo-pharyngeal reflexes. LM was correctly installed from the first attempt in 98.7% cases. In combined intravenous ketamine-based anesthesia, pressor reaction to LM installation consisted in an increase of heart rate by 5.6% (1K group--control), by 10.2% in 2K group (fractionated ketamine (1.5-2 mg/kg) + diazepam (0.1 mg/kg) and fentanyl (2.6 micrograms/kg); after barbiturates heart rate increased by 6.7% in 1B group (control), after diprivan it did not increase in 1D group (control), while the mean arterial pressure in 2D group (fractionated diprivan (1 mg/kg) + ketamine (25-50 mg), diazepam (0.08 mg/kg) and fentanyl (2.6 micrograms/kg) increased by 10% and heart rate by 6.6%. Reaction to tracheal intubation was pronounced in all types of induction anesthesia. No regurgitation or aspiration was observed in any case. Hence, use of total myoplegia in installation of LM allows the use of various modern anesthetics in optimal doses and notably simplifies the utilization of LM. PMID- 11220947 TI - [Hazards and complications of central segmental blockade. I. Epidural anesthesia (retrospective analysis)]. AB - A total of 700 reports about complications of epidural anesthesia over more than 30 years are analyzed. Four groups of complications have been distinguished: 1) errors and complications caused by technological errors; 2) complications caused by atypical dissemination of an anesthetic; 3) complications caused by side and toxic effects of local anesthetics or effects of epidural block; and 4) complications caused by damage to nerve structures. Causes, pathogenesis, prevention and treatment of complications are discussed. The cause-and-effect analysis of complications of epidural anesthesia helped objectively formulate and validate the relative and absolute contraindications to the use of this method. PMID- 11220948 TI - [Anesthesia in one-stage surgery of the carotid and coronary arteries]. PMID- 11220949 TI - [Acridonacetic acid: pharmacological properties and clinical use]. AB - The summarized data on the biological activity of acridoneacetic acid, a low molecular interferon inducer are presented: the amount and type of induced interferon, producer cells, interaction with viruses; the antiviral, antitumoral and anti-inflammatory activity of the preparation has been demonstrated. The specific features of interferon induction by virus (a biological inducer), in contrast to acridoneacetic acid (a chemical inducer) have been noted. The possible mechanisms of interferon induction by low-molecular interferonogen are considered. A number of interferonogens, salts of acridoneacetic acid, proposed as medicinal preparations are considered. The results of the clinical use of Cycloferon, a medicinal form of acridoneacetic acid, are presented. PMID- 11220950 TI - [Compatibility of vaccines in combined and associated immunization]. PMID- 11220951 TI - [Microflora of patients with purulent septic diseases in the Moscow region]. AB - The microflora of clinical material (blood, wound discharge, abdominal exudate, pleural exudate, milk in mastitis, as well as feces in dysbiosis of the large intestine), obtained from patients with purulent septic diseases in the Moscow region was studied. The study revealed the change of microflora from surface biotopes to closed cavities of the body. Gram-positive cocci, primarily coagulase negative staphylococci, mainly epidermal, were shown to play the leading etiological role in the development of purulent septic diseases. The development of bacteriemia was found to be caused by the penetration of staphylococci from local pyoinflammatory foci (appearing in purulent mastitis, wounds, peritonitis, pleural empyema and pleuritis), as well as by the translocation of staphylococci and Escherichia coli from the large intestine in dysbiosis. PMID- 11220952 TI - [Use of vaccination for prevention of viral hepatitis among students of vocational schools]. PMID- 11220953 TI - [Isolation v E. coli O157:H7, the causative agent of acute enteric infections with hemolytic-uremic syndrome in the Tula region]. PMID- 11220954 TI - [Water route of transmission of acute intestinal infections in Armenia]. PMID- 11220955 TI - [Epidemiological surveillance of outbreaks of acute intestinal infections: basic principles]. PMID- 11220957 TI - [Antilysozyme activity of anaerobic bacteria from fecal microflora in man]. AB - For the first time anaerobic bacteria of the fecal microflora in man have been found be capable of inactivating lysozyme. The presence of this antilysozyme sign has been noted in both Gram-positive anaerobes (Bifidobacterium, Propionibacterium, Eubacterium, Actinomyces israelii) and in Gram-negative anaerobes (Bacteroids, Prevotella melaninogenica). The expression of antilysozyme activity in the anaerobes under study has been determined. The possible biological role of this sign of the indigenous intestinal microflora has been discussed. PMID- 11220956 TI - [Common epitopes of protein antigens in Neisseria and Moraxella]. AB - Cross reactions between N. meningitidis and M. catarrhalis proteins were studied with the use of a panel of monoclonal antibodies to M. catarrhalis protein antigens. All antigenic preparations under study were shown to give cross reactions between N. meningitidis serotype porin of 39 kD (strain B125) and M. catarrhalis proteins of 40-41 kD. These M. catarrhalis proteins belonged to main proteins of class F and had the function of porins in the cell. In addition, the epitope of 41-kD antigen, detected by monoclonal antibodies 3E10, is common for both N. meningitidis porin and N. meningitidis iron-regulated proteins of 70 and 50 kD. The epitope of M. catarrhalis protein of 67 kD, detected by monoclonal antibodies 1G6, is common for N. meningitidis porin and N. meningitidis iron regulated proteins of 50 and 55 kD. PMID- 11220958 TI - [Microbiological monitoring of causative agents of sapronoses in the water of the Bogatinskoe water reservoir]. AB - The results of the microbiological monitoring of potential causative agents of sapronoses in the water of the Bogatinskoye reservoir revealed that in the summer period of 1998 the mass accumulation of virulent Aeromonas sobria (up to 25% of the total number of heterotrophic bacteria) took place. The autumn period was characterized by a decrease in the number of A. sobria and the detection of bacteria of the genus Vibrio (up to 22%) with V. mimicus and V. metschnikovii identified among them in the water ecosystems of the southern regions of the Maritime Territory. PMID- 11220959 TI - [Cholera in the Far East of Russia. Communication 1. Epidemiological characteristics of the outbreak of cholera El tor in Vladivostok]. AB - The materials on the investigation of the outbreak cholera eltor in Vladivostok, caused by the import of infection from China. The leading role of the water route of transmission of this infection is shown due to the contamination of water sources with non-decontaminated sewage water. The complex of antiepidemic measures was carried out, which made it possible to arrest the spread of cholera and liquidate its foci. PMID- 11220960 TI - [Autoregulation of expression of secreted proteins in Listeria monocytogenes]. AB - The spectrum of proteins secreted by L. monocytogenes greatly depends on the composition of the cultivation medium. The introduction of activated charcoal (AC) into brain heart infusion (BHI) leads to the secretion of a number of additional proteins with mol.wt. ranging between 20 and 100 kD, whose production is not observed in pure BHI. The effect depends on the absorption capacity of AC: when adsorption capacity is reduced due to a decrease in the concentration of AC or its preliminary saturation with the components of the cultivation medium a drop in the level of the production of additional proteins is observed. The preliminary treatment of the medium with AC with its subsequent elimination prior to inoculation doses not change the spectrum of secreted proteins, though greatly inhibits the growth of L. monocytogenes. The data obtained in this investigation indicate that the effect produced by AC is based on the elimination of some product of L. monocytogenes vital activity from the cultivation medium; this product acts as the autoregulator of the synthesis of a number of secreted proteins. PMID- 11220961 TI - [Cholera in the Far East of Russia. Communication 2. Epidemiological characteristics of the outbreak of cholera El tor in Iuzhno-Sakhalinsk]. AB - The outbreak of cholera eltor in Yuzhno-Sakhalinsk has been analyzed. The fact of the import of this infection from China and its transmission mainly by the water route due to the intensive contamination of environmental objects has been substantiated. The effective purification decontamination of sewage water plays decisive role on the system of anticholera measures. The conclusion on the necessity of increasing the effectiveness of measures for the sanitary protection of the territory has been made. PMID- 11220962 TI - [Spread of infection with hepatitis B and C viruses in different population groups of north-western Ukraine]. AB - The detection rate of specific markers of hepatitides B and C among the child and adult population, including 487 children in 5 boarding schools, 338 oncological, hematological, urological patients and 206 medical staff members in Rovno and the Rovno region (North-Western Ukraine), was determined. In boarding-school the markers of HB (HBsAg, anti-HBs, summary anti-HBc) were detected 3.5 times more often than among the child population in general (in 28.3 and 8.0% respectively). In children staying in a boarding school for up to 1 year (126 children) these markers were determined in 23% of cases, and in those who stayed there for 3-5 years, in 58.1% of cases. Among the members of the groups where children with HBsAg were found the markers of HB occurred 3.3 more often then among the children in the groups having no HBsAg carriers (45.3 and 13.9% respectively). The detection rates of the markers of HB in children with various kinds of C.N.S. pathology (first of all, with mongolism) and without concomitant diseases were sharply different (they were found, respectively, in 52.9 and 19.6%, including HBsAg in 17.4 and 2.7%). At the same time the detection rate of anti-HCV among boarding-school children (including those with C.N.S. lesions) was no different from that among the child population in general, which was indicative of great differences in the activity of the nonartificial transmission routes HB and HC viruses. Patients with oncological, hematological and urological diseases who had great "parenteral load", as well as medical staff members, formed a high risk group for being infected with both HB and HC viruses. PMID- 11220963 TI - [Comparative evaluation of the reactogenicity and immunogenicity of inactivated influenza vaccines in the elderly]. AB - A comparative study was carried out to assess reactogenicity and immunogenicity of inactivated influenza vaccines (Begrivac, Vaxigrip, Grippol, Influvac, and Fluarix), licensed in Russia. Immunization of the elderly demonstrated low reactogenicity and high immunogenicity for all vaccines. Concomitant chronic diseases had no influence on the vaccine immunogenicity levels, which testifies to the benefit of vaccination in this age group. In the group of vaccinated the highest seroconversion to all vaccine strains was found for Vaxigrip (82-89% for group A viruses and 86% for group B virus); the vaccine demonstrated the highest level of diagnostic increase of antibody titers to all 3 viruses, i.e. 69.0% (p < .05), with 22.0% of vaccinees gained antibodies to 2 vaccine viruses (91.0% in total). The number of positive responses to 3 and 2 strains in subjects immunized with Fluarix, Begrivac and Influvac reached 85.0%, 85.0% and 83.0% respectively. It is noteworthy that the combination of surface antigens of A and B flu viruses in low concentration with polyoxidonium immune modulator in Grippol induced intensive immune response. PMID- 11220964 TI - [Characteristics of immune response to diphtheria anatoxin in children with different immune status during the second age-scheduled revaccination]. AB - The dynamics of the intensity of specific antidiphtheria immunity after the second age-scheduled revaccination was studied in 129 practically healthy children. The study revealed that the formation of immunity depended on the initial functional state of the immune system before the injection of diphtheria toxoid. Three variants of immune response were determined and the immune status corresponding to each of these variants was characterized. As shown in this study, children with the hyperergic character of immune response were characterized by relatively high initial titers of antitoxin, and the injection of an additional dose of the antigen led to the prolonged state of hyperimmunization with the subsequent decrease of the intensity of immunity by half, registered in the catamnestic observation for 4 years. Children with the hypo- and normoergic variants of immune response were characterized by the most stable immune response to diphtheria toxoid, and during the catamnestic observation they formed the levels of antibody titers 2.5- to 3-fold higher than before immunization. But the protection characteristics in children with the third variant were the lowest among the children under study. PMID- 11220965 TI - [Protective efficacy of combined administration of the multicomponent vaccine and the immunomodulator myelopid in experimental infections in mice]. AB - The influence of myelopid (MP) on the protective activity of polycomponent vaccine VP-4 prepared from the antigens of opportunistic bacteria was studied on experimental infections of mice, caused by Klebsiella pneumoniae, Salmonella typhimurium and Staphylococcus aureus. In staphylococcal and Klebsiella infections the joint administration of vaccine VP-4 and MP produced more pronounced protective effect than each of these preparations, introduced alone. The protective action of vaccine VP-4 was specially enforced by MP in cases of local staphylococcal infection. Recommendations on the joint use of two or more immunomodulating agents are possible only on the basis of the experimental substantiation of their effect in definite infections. PMID- 11220966 TI - [Changes in the functional activity of neutrophils during their interaction with Yersinia pestis in vitro]. AB - The functional state and electrochemical properties of human blood neutrophil leukocytes after their in vitro interaction with Y. pestis cells, strain EV, was analyzed. A considerable decrease in the electrophoretic mobility of neutrophil leukocytes and a considerable increase in their phagocytic indices was shown. At the same time the maximum phagocytic activity in the total pool of isolated neutrophil leukocytes was registered in fractions having higher electrophoretic mobility. The dependence of electrophoretic mobility on the state of neutrophil membranes, as well as the degree of their activation, is discussed. PMID- 11220967 TI - [The role of the protein with molecular weight of 22 kD in the phagocytosis of vaccine strain of Yersinia pestis EV]. AB - The comparative study of different stages of the phagocytosis of vaccine strain Y. pestis EV and its achromogenic variants (AV), has been carried out with the use of peritoneal macrophages as an in vitro experimental model. As revealed in this study, AV whose outer membrane contains no protein with a molecular weight of 22 kD exhibit lower capacity for adherence and for being ingested by phagocytes than the initial strain. The absence of this protein does not inhibit the multiplication of AV inside phagocytes, leading to incomplete phagocytosis, which is characteristic of the initial strain. The suggestion is made that the 22 kD protein may be one of the adhesion factors, necessary for ensuring the initial stages of phagocytosis. PMID- 11220968 TI - [The use of liposomal form of phenylimide of cis-aconitic acid in herpes therapy]. AB - The results of study of the antiviral activity and pharmacokinetics of phenylimide of cis-aconitic acid (PCAA) is presented. The 20% increase of the antiviral activity of PCAA incorporated into liposomes in comparison with the antiviral activity of the pure substance was shown. Liposomes with PCAA were tropic to lymphocytes and macrophages with maximum fluorescence being observed in the spleen, while empty liposomes were accumulated mainly in the liver. After the treatment with liposomal PCAA the symptoms of herpetic meningoencephalitis became less severe with 100% survival of the experimental animals. In the control group of rabbits 50% of the animals died, and in the surviving animals blindness or paralysis developed. PMID- 11220969 TI - [Possibility of existence and multiplication of Mycobacteria in the soil]. AB - The time of the survival of Mycobacterium bovis in the soil of pastures depended on the physicochemical composition and biological activity of the soil. In clay soils M. bovis retained their virulence for as long as 2 months (at the depth of 2 cm in high- and medium-posted solonetz) to 12 months (at the depth of 10 cm in crust solonetz). The M. bovis strains under study multiplied in soil extracts (the term of observation was 8 months). The cultures grown at 20-24 degrees C were found to have the prolonged exponential phase in comparison with that of the cultures grown at 37.5-38.5 degrees C. In the deep litter and the soil under it M. avium remained viable for 10 years. PMID- 11220970 TI - [Microbial biocenosis of the nasal mucosa in healthy persons and in Staphylococcus carriers]. AB - The normal microflora of the nasal mucosa in man is differentiated into main, complementary and casual microflora, taking into account its isolation rate and characteristics of microbial contamination. The main microflora of adults, in contrast to children, is represented, in addition to coagulaso-negative (CN) staphylococci, by bacteria of the genus Corynebacterium. In staphylococcal carrier state a decrease in the isolation rate and the amount of bacteria belonging to the main and complementary microflora (CN staphylococci, Micrococcus, Streptococcus, Bacillus) was observed. Moreover, in carriers the weakening of the degree of association between CN staphylococci, Micrococcus, Corynebacterium, Streptococcus in symbiotic pairs was noted. In the absence of S. aureus carrier state the main and complementary microflora was characterized by the combination of the factors of antagonism and persistence, while in carrier state the complex of colonization factors was defective in the main microflora and well pronounced in coagulase-positive staphylococcal strains and enterobacteria. PMID- 11220971 TI - [The use of biological preparations for correction of microbial status in pregnant women]. AB - 15 pregnant women with pregnancy lasting 28-32 weeks, whose medico-laboratory data (the positive result of the amino test, high pH value and the detection of "key" cells) suggested the presence of bacterial vaginosis, were placed under observation. The bacteriological study of vaginal microflora in all these women revealed pronounced disturbances simultaneously with the development of intestinal dysbacteriosis. The local application of the bacterial preparation "Zhlemik" containing freeze-dried live lactic acid bacteria of vaginal origin and the oral administration of lactic acid bifidumbacterin containing live bifidobacteria of intestinal origin permitted the successful restoration of vaginal and intestinal microbiocenosis. The capacity of biotherapeutic preparations for inducing non-specific immunostimulation led to a significant rise in the levels of IgA, IgM and IgG in vaginal secretions. PMID- 11220972 TI - [Comparative characteristics of protein G gene in Streptococci of groups C and G isolated from humans]. AB - The treatment of streptococci, groups C and G, with bromocyanogen made it possible to isolate surface G protein, capable of binding human serum albumin (HSA) and polyclonal IgG. In this work the presence of G protein in all staphylococcal strains, groups C and G, is shown. The differences between the strains by the level of expression, molecular weight and functional activity of G protein, extracted from streptococci of groups C and G, permitted the identification of 3 groups of strains, containing the molecules of G protein with different numbers of IgG- and HSA-binding domains: with 3 IgG- and HSA-binding domains, with 2 IgG- and HSA-binding domains and with only 2 IgG-binding domains. Each strain under study expressed only one of the molecule of G protein. The work shows the possibility of the identification of streptococci, groups C and G, by the molecular characteristics of G proteins themselves and their respective coding genes. PMID- 11220973 TI - [The use of polymerase chain reaction in the diagnosis of diphtheria infection]. AB - 624 Corynebacterium diphtheriae strains, newly isolated from patients and carriers, were studied with the use of the methods of gel immunodiffusion (Elek's test) and polymerase chain reaction (PCR). In the evaluation of 388 C. diptheriae strains, found to be toxigenic in PCR, the results of Elek's test coincided with those of PCR on 98% of cases. In 38 out of 143 strains (26.5%), nontoxigenic according to the results of Elek's test, the presence of the A-fragment of the tox-gene was established. Subculturing in nutrient media made it possible to determine the presence of toxin in 19 out of 38 of these strains; the remaining strains, isolated mainly from carriers, were found to have the "silent" gene. The advantage of using PCR for the detection of toxigenic and nontoxigenic C. diphtheriae strains of different origin was shown. PMID- 11220974 TI - [The use if Francisella tularensis lipopolysaccharide in the dot solid phase enzyme immunoassay]. AB - To determine antitularemia antibodies in the sera of humans and animale, the possibility of using dot immunoassay with the use of F. tularensis lipopolysaccharide (LPS) as antigen-containing preparation was ascertained. Experiments demonstrated that this method made it possible to determine specific antitularemia antibodies in the sera of sick and immunized humans and animals. Investigetions carried out with the use of heterologous antisera to F. novicida, F. novicida-like and F. philomiragia, as well as Brucellf abortus, Vibrio cholerae and Yersinia enterocolitica, revealed that F. tularensis S-LPS was highly specific. The results obtained in this investigation are indicative of good prospects of using F. tularensis LPS in dot blotting for the laboratory diagnostics of tularemia in humans. PMID- 11220975 TI - [Allergic sensitivity in different groups of patients with atopic dermatitis]. AB - 69 patients with atopic dermatitis, aged 16-42 years, were examined. The patients were divided into two groups: group 1 consisted of patients with atopic dermatitis and bronchial asthma and/or allergic rhinitis (25 patients), group 2 consisted of patients without the respiratory syndrome (44 patients). Scarification skin tests made it possible to find out the essential difference in the sensitivity of the examinees in these two groups. In group 1 the prevalence of sensitization to house-dust mites in 23 patients (92%) with monosensitization in 8 patients (32% of the group) was observed. In group 2 sensitivity of house dust mites was lower: it was registered in 16 patients (36%) with monosensitization in 2 patients (4% of the group). The presence of cross sensitivity between mite allergens and Candida albicans was established. In accordance with the results of scarification skin tests, treatment included the use of antihistamine preparations, antipruritic remedies and hormonal ointments as well as the elimination of sensitizing allergens. Improvement was registered in 21 patients. PMID- 11220976 TI - [The role of oleic acid in the process of induced destruction of Escherichia coli M-17]. AB - The influence of oleic acid on the process of the destruction of E. coli, induced by the transfer of the bacteria from the growth medium into solution without nutrient substances and their treatment with oleic acid at a temperature of 45 degrees C, was studied. Oleic acid at a concentration of 200 nmol/ml accelerated the destruction of E. coli in comparison with the control organisms, but did not lead to the significant increase of the final degree of the destruction of biomass. The dynamics of the inclusion of labeled oleic acid into E. coli cell fractions after the induction of autolysis was analyzed. The radioactive label was most actively included into the lipid (chloroform) fraction of bacterial biopolymers. Simultaneously with the destruction of some cells in the population the inclusion of labeled oleic acid into intact cells was found to occur. PMID- 11220977 TI - [Bactericidal properties of the Vibrio cholerae non O1 bacteriolysin]. AB - The influence of the preparation of hemocytolysin, obtained from V. cholerae non O1 (strain P-11702), on the growth of V. cholerae cells was studied. The study revealed that hemocytolysin is capable of inducing partial or complete bacterial lysis on the place of its application, depending on the protein load of the substance and the inoculation dose of microbes. Two electrophoretic fractions with molecular weights of 14 and 14.5 kD induced the cytolysis of sheep, rabbit, guinea-pig red blood cells and showed a bactericidal effect. The different sensitivity of Vct+ and Vct- strains of V. cholerae to different doses of hemocytolysin was studied. PMID- 11220978 TI - [Genetic markers of epidemic strains of Vibrio cholerae]. AB - In this review new data on the key pathogenicity genes of V. cholerae are presented. As shown on the basis of the analysis of the latest information on the structure of the genomes of different V. cholerae strains, structural genes ctxAB coding cholera toxin may not serve as the only marker of epidemically dangerous strains. More complete and reliable information for the evaluation of the epidemic potential of V. cholerae isolated from the environment may be obtained by the simultaneous detection of 4 genetic markers: genes ctxAB, tcpA and hap coding, respectively, cholera toxin, toxin-corregulated adhesion pili and soluble hemagglutinin/protease, as well as regulatory virulence gene toxR. PMID- 11220979 TI - [Factors and genetics of pathogenicity of group B Streptococci]. AB - In this review data on the pathogenicity factors of streptococci and their genetic control are presented. Attention is paid mainly to protein antigens alpha and beta, C5a peptidase, CAMP factor, R, Rib and X proteins. The problems of making the genetic and physical charts of the genome of group B streptococci, the genetic regulation of the synthesis of pathogenicity factors and the specific features of the damaging action of the infective agent are discussed. PMID- 11220980 TI - [Immunity in listeriosis]. AB - In this review modern concepts on the formation of specific immunity to listeriosis are presented. Numerous data indicate that in Listeria monocytogenes virulence and the capacity for inducing specific protection is ensured by the protein listeriolysin O. The importance of gamma-interferon, tumor necrosis factor alpha, interleukin 12 and other mediators in ensuring the differentiation of (CD4(+) T-cells into Th1-helpers and cytotoxic T-lymphocytes in animals infected with L. monocytogenes is described in detail. The safety and effective preparations for specific prophylaxis of listeriosis were not developed. Hopeful results have been obtained in experiments on the immunization of mice with killed bacteria with listeriolysin O or interleukin 12. Works describing the use of modified L. monocytogenes strains as vectors for the creation of vaccines against different infections seem to show good prospects. PMID- 11220981 TI - Child abuse--a political, parental and religious syndrome. PMID- 11220982 TI - Sildenafil citrate (Viagra) is effective and well tolerated for treating erectile dysfunction of psychogenic or mixed aetiology. AB - Sildenafil citrate (Viagra) has been shown to be an effective treatment for erectile dysfunction (ED) of organic aetiology. This study assessed the efficacy and tolerability of sildenafil for treating ED of psychogenic and mixed psychogenic/organic aetiology. Men with ED of psychogenic and mixed aetiology were randomised in a double-blind, fixed-dose study to placebo (n = 95) or sildenafil 10 mg (n = 90), 25 mg (n = 85), or 50 mg (n = 81) once daily for 28 days. Efficacy was evaluated with two global efficacy questions, a patient log of erectile activity, a sexual function questionnaire and a partner questionnaire. Patients receiving sildenafil had significantly more grade 3 (hard enough for penetration) or grade 4 (fully hard) erections per week than patients receiving placebo, and a greater proportion of patients receiving sildenafil reported that treatment had improved their erections (p < 0.001). Results of the sexual function questionnaire demonstrated significant improvement for patients with ED receiving sildenafil compared with patients receiving placebo for frequency, hardness and duration of erections (p < 0.01), and for enjoyment of sexual intercourse and satisfaction with sex life (p < 0.05). The results of the partner questionnaire were consistent with the results reported by patients and showed that treatment with sildenafil was associated with significant improvement in the partners' own sex lives (p < 0.001). Adverse events were mostly mild to moderate in nature. The commonest adverse events were headache, dyspepsia, flushing, myalgia, arthralgia and flu syndrome. Discontinuations due to treatment-related adverse events were few, ranging from 1.1% to 6.2% for patients receiving different doses of sildenafil and 4.2% for patients receiving placebo. Sildenafil is an effective and well-tolerated treatment for ED of psychogenic or mixed aetiology with once-daily dosing. PMID- 11220983 TI - Multicentric study of the effect of milk fermented by Lactobacillus casei on the incidence of diarrhoea. AB - The aim of this study was to determine if supplementation of healthy children with milk fermented by yogurt cultures and Lactobacillus casei strain DN-114 001 could affect the incidence of acute diarrhoea when compared with traditional yogurt. The study was a multicentre, randomised, double-blind trial, conducted over four months, on 928 children aged, at inclusion, 6-24 months. The study consisted of two periods: supplementation and observation. Subjects were supplemented daily with 100 g of one of the two dairy products being tested: standard yogurt and milk fermented by yogurt cultures and Lactobacillus casei (10(8) cfu/ml). Frequency or duration of any diarrhoea episode was evaluated. As far as frequency was concerned there was a statistically significant difference between the groups, the incidence of diarrhoea being significantly reduced by supplementation with L. casei fermented milk (15.9%) compared with yogurt (22%) (p = 0.03). These results suggest an additional benefit of L. casei in acute diarrhoea in children compared with standard yogurt. PMID- 11220984 TI - The impact of a structured programme of asthma care in general practice. AB - The impact of a new GP programme of asthma care was examined using: a) a retrospective pre- and post-casenote survey of 400 asthma patients, comparing patients in practices using the health board programme (HBP) and other programmes (OP); and b) a patient satisfaction questionnaire, completed by 532 people on asthma clinic lists in HBP and OP practices. Outcomes assessed were health service use, perceived change in symptoms and asthma self-management. The casenote survey indicated improved health service use by patients in HBP practices, with fewer patient-initiated (p < 0.05), emergency (p < 0.05) and other chest-related attendances (p < 0.01) and increased clinic attendance (p < 0.05) post intervention. OP practices also showed reduced patient-initiated (p < 0.01) and increased asthma clinic use (p < 0.01). Increased use of management plans (p < 0.01) and peak flow diaries (p < 0.01) was noted post intervention for HBP practices. Responders to the questionnaire survey perceived that clinic attendance improved asthma symptoms, including severity and control, sleep disturbance and early morning wheeze. People in HBP practices were more likely than those in OP practices to possess a peak flow meter, a diary and a personal management plan (all p < 0.01 or above) but were not more likely to use a peak flow diary. Notwithstanding methodological difficulties in the selection of practices, both studies showed trends towards improvement in health service use and asthma self-management. The HBP was associated with greater improvement in self-management processes and outcomes, and greater patient satisfaction with asthma care. PMID- 11220985 TI - Latex allergy: an emerging problem in theatres. AB - With the increasing use of natural rubber products, latex allergy is becoming a major health concern among patients and healthcare workers. The aim of this study was to determine the availability of a latex allergy protocol and essential latex free products in theatres. The number of latex allergy complaints among patients and theatre personnel were also studied. Postal questionnaires were sent to theatre managers in 205 hospitals in England, Scotland and Wales, 120 (58.5%) of which were returned. Nearly two-thirds of the theatres did not have a latex allergy protocol. Overall less than one-third of theatres in the UK have latex free products set aside for use. A total of 505 patients with latex allergy underwent surgery; of these, there were four deaths, 18 major anaphylaxes and 483 minor complaints such as skin rash; 239 theatre personnel reported latex allergic reactions and one had a severe anaphylactic reaction. The number of cases with latex-related complications might be reduced if all hospitals had a latex allergy protocol and a range of essential latex-free products. PMID- 11220986 TI - Oral antimicrobial susceptibilities of Streptococcus pyogenes recently isolated in five countries. AB - Between July 1998 and July 1999 1050 clinical isolates of Streptococcus pyogenes were collected from 11 study centres in five countries. Isolates were shipped to a co-ordinating laboratory for NCCLS specified broth microdilution susceptibility testing for penicillin, cefaclor, azithromycin, clarithromycin, erythromycin and roxithromycin. All 1050 isolates of S. pyogenes tested were susceptible to penicillin (MIC < or = 0.12 microgram/ml) and cefaclor (MIC < or = 0.25 microgram/ml). Azithromycin, clarithromycin and erythromycin resistance rates were 15.9%, 15.4% and 15.8%, respectively. MIC90S for penicillin, cefaclor, azithromycin, clarithromycin, erythromycin, and roxithromycin were 0.015, 0.12, > 4, 8, > 1 and 16 micrograms/ml, respectively. Macrolide (erythromycin) resistance rates were highest in study centres in Italy (31.0%) and Spain (26.6%). Lower macrolide resistance rates were identified in study centres in Turkey (4.8%), France (3.8%), and Sweden (3.7%). In conclusion, the isolates of S. pyogenes tested were universally susceptible to beta-lactam antibiotics such as penicillin and cefaclor, while resistance to macrolides was significant and ranged from 3.2% to 31%. PMID- 11220987 TI - Growth factors in clinical practice. AB - Wound repair consists of a complex interaction of cellular and biochemical events. Several growth factors have been identified as regulatory polypeptides co ordinating the healing process. Although it is not known precisely why chronic wounds do not follow the normal pattern of healing, diminished growth factor content and accelerated growth factor degradation may contribute to poor healing. Topical application of different factors exert stimulatory effects on wounds in animal models. Human data are limited but the most investigated compound is recombinant human platelet-derived growth factor-BB (rhPDGF-BB). PDGF-BB enhances granulation tissue formation and facilitates epithelialisation. Clinical trials in patients with 'hard to heal' diabetic foot ulcers demonstrated significant improvement in the 'healing rate' and the 'time to healing' compared with controls. Refinement of therapeutic strategies with growth factors will take place in the future. PMID- 11220988 TI - Steroidal contraception for men. AB - This article is a review of the development of male steroidal contraceptives during the past 25 years. Numerous studies have been conducted on male volunteers with oral and/or injectable preparations of single or combined steroids. Progestogen, androgen alone, or progestogen and androgen combinations have been used as weekly or monthly injectable formulations. Most of the studies involved small numbers of subjects. There was reversible suppression of spermatogenesis to oligospermia and/or azoospermia during the treatment period. Alteration of LH, FSH and testosterone levels in the blood was observed in most of these studies, depending on the steroid or combination of steroids used. There were reports about decreased or increased libido and weight gain during treatment with steroids. No other serious side-effects were found. Attention has recently focused on developing an androgen-only male contraceptive, because testosterone ester has shown promising results. The development of an effective and reliable steroidal contraceptive for men may be possible but this requires further research. PMID- 11220989 TI - Neuraminidase inhibitors: progress in the management of influenza. AB - Influenza is a serious respiratory illness and represents a significant clinical burden. As well as being debilitating, influenza can often cause complications leading to hospitalisation and death. Prophylaxis by vaccination is the preferred method of disease management, but because influenza viruses are constantly changing their antigenic properties, influenza outbreaks occur regularly as epidemics. Neuraminidase inhibitors are a new class of anti-influenza drugs designed to block influenza virus replication. Two neuraminidase inhibitors, zanamivir and oseltamivir, have been licensed for clinical use in the treatment of influenza. Both drugs significantly reduce the severity and duration of the illness when treatment is started within two days of the onset of symptoms. However, while zanamivir and oseltamivir have apparently similar efficacy, they differ in their modes of delivery and tolerability. Zanamivir is delivered direct to the lungs by inhalation and is well tolerated. Oseltamivir is taken in the form of a pill but has the side-effect of producing nausea and vomiting in some patients. In the absence of a demonstrable difference in efficacy, uptake of the two drugs will depend on evaluation of the relative merits of mode of delivery and tolerability. PMID- 11220990 TI - Prostate-specific antigen and prostate cancer. AB - Serum prostate-specific antigen (PSA) measurement is used to investigate patients with lower urinary tract symptoms and to screen for prostatic malignancy in symptom-free males over 50 years of age. Approximately 60% of patients with early (prostate-confined) occult malignancy show increased serum PSA levels, as do some 20% of patients with prostatic symptoms from benign prostatic disease. When PSA is only slightly raised, serial PSA measurements, correction for prostatic volume and especially measurement of free (unbound) PSA (which is reduced in prostatic malignancy) may assist the differentiation of prostatic cancer from benign hypertrophy. Serial measurements are also of value for monitoring treatment of prostate cancer and for post-treatment surveillance. PMID- 11220991 TI - Pioglitazone. AB - Pioglitazone is a thiazolidinedione. As a PPAR-gamma agonist it alters the expression of a number of genes, resulting in a reduction in insulin resistance. Clinical trial data involving over 4500 patients with type 2 diabetes suggest it is effective both as monotherapy and in combination with sulphonylureas, metformin and insulin, producing both significant falls in HbA1c and favourable improvements in lipid parameters. It is well tolerated, with a low incidence of side-effects. Unlike troglitazone, its use has not been associated with hepatotoxicity. It has recently been licensed in the US for use as monotherapy and in combination with insulin, metformin and sulphonylureas. Its European license is more restrictive, allowing use in combination with metformin, and in combination with sulphonylureas in those intolerant of metformin. It provides a useful new option in the treatment of type 2 diabetes mellitus. PMID- 11220992 TI - A case of recurrent impetigo herpetiformis with a positive family history. AB - Impetigo herpetiformis is a rare non-infectious pustular dermatosis of pregnancy. A few non-gestational cases due to oral contraceptive use have also been reported. Although the disorder is not thought to have a genetic background, there are some familial case reports in the literature. We describe a case of recurrent impetigo herpetiformis in an 18-year-old pregnant woman who had normal serum calcium levels and responded well to prednisolone therapy. Interestingly, the patient's mother had also experienced a generalised pustular dermatosis associated with hypocalcaemia during oral contraceptive use, which was diagnosed clinically and histologically as impetigo herpetiformis. PMID- 11220993 TI - Recurrent encephalopathy and generalised seizures associated with relapses of thyrotoxicosis. AB - Seizures or encephalopathy associated with thyrotoxicosis are very rare. A 30 year-old man with thyrotoxicosis and strongly positive thyroid antibodies presented with generalised seizures preceded by an encephalopathic illness of a few days duration. CSF protein was raised and EEG showed bilateral slowing of activity. Antithyroid drug treatment rendered him biochemically euthyroid, his cognitive state returned to normal and his seizures stopped. Subsequently he had a recurrence of both encephalopathy and seizures on two occasions, coinciding with relapses of the thyrotoxicosis. This supports the view that the hyperthyroid state caused this serious neurological condition. Treatment with 131I caused hypothyroidism and he has remained seizure free and well for six years on thyroxine replacement. Corticosteroids may have been helpful in the management of his encephalopathy. PMID- 11220994 TI - A case of isolated ACTH deficiency presenting with hypercalcaemia. AB - A 76-year-old man presented with a subacute history of weight loss, malaise and anorexia. Laboratory investigations revealed serially increasing hypercalcaemia, correlating with deterioration in his clinical status. He was subsequently shown to have hypocortisolaemia, which improved with the administration of intravenous steroids. Subsequent biochemical testing revealed the endocrinological defect to be one of isolated ACTH deficiency, which, unlike Addison's disease, does not classically include hypercalcaemia in its presentation. PMID- 11220995 TI - Strangulated inguinal hernia complicating colonoscopy. PMID- 11220996 TI - [Ehrlichiosis--new infectious pathology in Russia]. PMID- 11220997 TI - [Ecological aspects of human pathogens Ehrlichia and Bartonella]. AB - The review presents data on the natural circulation of Bartonellas and Erlichias with the participation of lice, fleas, mosquitoes, Ixodes ticks, as well as rodents, large wild mammals, and domestic animals. It outlines the human infection routes that are mainly associated with the attack of infected carriers and with the contacts with different warm-blooded animals. The risk of bartonellosis spread is evidenced by the data showing that 12.3% of clothes lice collected from homeless individuals in Moscow turned out to be infected. In a focus of erlichiasis, the infection rates of Ambliomma americanum and Ixodes scapularis were 4.9 and as high as 20%, respectively; 100% of white-tailed deers (Odocoileus virginianus) were seropositive. However, many issues associated with the preservation of these natural vectors, with the route of their transmission to human beings and animals are to be studied. PMID- 11220998 TI - [Relationship between zoonotic cutaneous leishmaniasis morbidity in the Murgab oasis and hydrometeorological factors]. AB - The relationships of changes in the incidence of zoonotic cutaneous leishmaniasis (ZCL) in the Mary velayat, Turkmenistan, to those in hydrometeroelogical factors in 1951 to 1993 were first analyzed and the regularities found were evaluated. There is an inverse relationship of the incidence to the temperatures of the preceding winter. The long persistence of sun shining seems to have a negative impact on the foci of ZCL. There is an insignificant correlation of humidity, precipitation, and winds. In the years marked by high waters in the valley foci, increased soil moisture content causes a reduction in their epidemic activity. PMID- 11220999 TI - [Landscape and geographical distribution of natural reservoirs of human vector borne diseases in Southern Kazakhstan and Kirghizia]. AB - The paper presents data available in the literature on the natural foci of plague, tularemia, tick-borne spirochetosis, Crimean hemorrhagic fever, tick typhus, Q fever, zoonotic cutaneous leishmaniasis. The largest number of transmissible infections is shown to be in the natural areas of deserts and piedmont semiarid lands. PMID- 11221000 TI - [Actual problems in diagnosis and treatment of imported malaria]. AB - Analyzing 66 cases of imported malaria, recorded among the patients treated at Moscow Infective Clinical Hospital No. 1 has indicated that despite its typical clinical picture and specific epidemiological history, the prehospital diagnosis of tropical and vivax malaria was correctly made in 20 and 22% of patients, respectively. As few as 3 patients had chemoprophylaxis on an individual basis during their stay in the focus, but they did not comply with the regimen recommended. The severity of the disease, in non-immunized patients with tropical malaria, in particular, is related to the time of admittance (diagnosis) and to that of the initiation of adequate specific treatment. PMID- 11221001 TI - [Establishment of the plague control system in Russia]. AB - The specialized plague control facilities which began being founded as a system of institutions in Russia in 1897 have made a great contribution to epidemiological well-being against quarantine and particularly menacing diseases. The developmental stages of plague control service in different periods of the country's social life and its place in the general governmental preventive and antiepidemic measures are shown. The paper emphasizes that it is expedient to maintain the antiepidemic readiness of plaque control facilities due the fact that the epidemic situation is due menacing and zoonosis is expected to aggravate in the late 20th to the early 21st centuries. PMID- 11221002 TI - [Culture of Plasmodium berghei with the short life span in mouse erythrocytes: evaluation of chloroquine resistance in three strains of the malaria parasite]. AB - This comparative study was made to examine chroloquine inhibition of C14 hypoxanthine incorporation (preferably nucleic acid precursor for plasmodium) in the short-living red blood cell cultures in mice infected with P. berghei strains differently sensitive to the agent 24 hours after incubation. These included 1) chloroquine-sensitive H strain; 2) LNK-65 strain having a spontaneously 2-3-fold decreased sensitivity to the agent; 3) strain LNK-65 ChR selected for high resistance to chloroquine. IC50 (chloroquine concentrations that ensure 50% inhibition of the incorporation of nucleic acid precursor into the cells of the parasite) was estimated for 3 P. berghei strains that were differently sensitive to chloroquine. These in vitro values adequately reflect the sensitivity of these strains to the agent in vivo. PMID- 11221003 TI - [Clinical and morphological characteristics of migrating erythema in patients with Ixodes tick-borne Lyme disease]. AB - Patients with erythematous Ixodes tick-borne relapsing fever were examined and their skin biopsy specimens were morphologically studied to reveal clinical, immunological and morphological features of erythematous Ixodes tick-borne relapsing fever. Two types of development of erythema migrans were identified. These include 1) a typical type that appears as an area of homogenous hyperemia or that of annular shape and 2) an atypical one that presents as minor vesicles. There were elevated serum immunoglobulins A levels at the height of the disease. Morphologically, at the early stage of the disease, the center of erythema shows disturbances characterized by epidermal dystrophic processes, koilocytosis, subhorny and epidermal vesicles. The dermis displays solid perivascular lymphocytic infiltrates admixed with fibroblasts, fibrocytes, macrophages, plasmocytes, eosinophils, degranulated labrocytes. The interstitium exhibits scanty infiltrates. These changes are less pronounced at the periphery. Electron microscopy shows the structures morphologically similar to those of Borrelia. The late stage (days 15-23) of the disease is marked by insignificant dystrophy and perivascular fibrosis. There were no interstitial infiltrates. By and large, the pattern of clinical and immunological manifestations in patients with erythema migrans correlates with dermal morphological changes. PMID- 11221004 TI - [Enzyme immunoassay in diagnosis of opisthorchiasis. Communication 2. Enzyme immunoassay test system for diagnosis of acute opisthorchiasis]. AB - A standard, highly specific and sensitive enzyme immunoassay test system has been developed for the diagnosis of acute opisthorchiasis, which is based on indirect solid-phase enzyme immunoassay for determination IgM antibodies to the antigen derived from Opisthorchis felineus marita extracts. The sensitivity of the test system is 87%, its specificity is 96.8%. PMID- 11221005 TI - [Synthesis and ovicidal effect of 8-aryloxyquinoline derivatives]. PMID- 11221006 TI - [Trichinella pseudospiralis--a possible trichinellosis pathogen in Russia]. PMID- 11221007 TI - [Use of the recombinant bacterial strain to control blood-sucking mosquito larvae]. AB - The recombinant strain of Methylobacillus flagellatum with the cloned synthesis gene Cry 4B of the toxic Bac. thuringiensis var. israelensis protein proved to be effective against larvae of the Anopheles stephensi, An. atroparvus, An. pulcherrimus, An. superpictus, and An. sacharovi cultured in the laboratory. The use of M. flagellatum in combination with T. pyriformis may greatly expand the scope of use of the recombinant strain to control malaria mosquito larvae. Their combined use shows a 6-fold increase in the rate of strain action and a 4-fold decrease in the concentration of the agent. The optimum effects are shown following 24-hour combined intubation of M. flagellatum and Tetrahymena pyriformis. PMID- 11221008 TI - [Characteristics of phagocytosis of Yersinia pseudotuberculosis with various sets of plasmids]. AB - The study used the selected aplasmid strain of Y. Pseudotuberculosis 53 and I 716, which contains plasmids that have molecular weights of 48 and 82 mD, and I 727 that has only virulence plasmid pYV48. The study has indicated that the fact that Yersinias have pVM82 and pYV48 enhances their resistance to phagocytosis. The Y. pseudotuberculosis strains carrying these plasmids suppress the responsiveness of phagocytes, inhibit an "oxidative explosion", lower the activities of superoxide dismutase and myeloperoxidase, thus suppressing their bactericidal capacity. PMID- 11221009 TI - [Criteria for classification of infectious diseases and infections which require measures for sanitary protection over the territory of the Russian Federation]. PMID- 11221010 TI - Combined quality improvement ratio: a method for a more robust evaluation of changes in screening rates. AB - INTRODUCTION: It has been proposed that a ratio of the discordant cells from a McNemar's Chi-square table be used as a measure of quality improvement, and that this measure be called the Quality Improvement Ratio (QuIR). As proposed, patients enrolled in only one year of a two-year study are excluded from the McNemar's table of the QuIR. Since the original proposal of the McNemar's Chi square in 1947 included application to matched pair data, a more comprehensive analysis would be possible if the single-year enrollees were matched into pairs. METHODS: Patients enrolled in only the first study year are matched and paired with patients enrolled in only the second study year. The pairs are matched on variables important to the disease or process being evaluated. The matched pairs are combined with the repeatedly measured subjects to increase the statistical power of the analysis. The Combined Quality Improvement Ratio (CQuIR) is demonstrated with parameters from the original articles, in a--Markov chain Monte Carlo simulation, so a direct comparison can be made. RESULTS: CQuIR improved statistical power, especially in simulations of small populations. In some simulations the statistical power was double that of the QuIR alone. DISCUSSION: Although the QuIR provides important information, the CQuIR allows more of the data to be used to evaluate the effect of interventions in policy, delivery, and practice. The increase in statistical power of the CQuIR over the QuIR can facilitate successful evaluation of health care services. PMID- 11221011 TI - Using quality management to balance the economic and humane imperatives in behavioral health care. AB - The authors describe how quality management can be used to achieve an ethical balance between economic pressures and high-quality patient care. PMID- 11221012 TI - Quality improvement in chronic illness care: a collaborative approach. AB - BACKGROUND: Despite rapid advances in the clinical and psycho-educational management of diabetes, the quality of care received by the average patient with diabetes remains lackluster. The "collaborative" approach--the Breakthrough Series (BTS; Institute for Healthcare Improvement [IHI]; Boston)--coupled with a Chronic Care Model was used in an effort to improve clinical care of diabetes in 26 health care organizations. METHODS: Descriptive and pre-post data are presented from 23 health care organizations participating in the 13-month (August 1998-September 1999) BTS to improve diabetes care. The BTS combined the system changes suggested by the chronic care model, rapid cycle improvement, and evidence-based clinical content to assist teams with change efforts. The characteristics of organizations participating in the diabetes BTS, the collaborative process and content, and results of system-level changes are described. RESULTS: Twenty-three of 26 teams completed participation. Both chart review and self-report data on care processes and clinical outcomes suggested improvement based on changes teams made in the collaborative. Many of the organizations evidencing the largest improvements were community health centers, which had the fewest resources and the most challenged populations. DISCUSSION: The initial Chronic Illness BTS was sufficiently encouraging that replication and evaluation of the BTS collaborative model is being conducted in more than 50 health care systems for diabetes, congestive heart failure, depression, and asthma. This model represents a feasible method of improving the quality of care across different health care organizations and across multiple chronic illnesses. PMID- 11221013 TI - Increasing understanding of patient needs during and after hospitalization. AB - BACKGROUND: The value of patient satisfaction surveys in health care improvement remains controversial. This study examined the value of alternative ways of identifying patient needs and estimating importance of those needs in improving the impact of satisfaction surveys. METHODS: Ninety-one acute myocardial infarction (AMI) patients from three southeast U.S. community hospitals were surveyed in 1992. Critical incident and person-focused interviews were used to identify patient needs. Besides overall/global satisfaction with care, patients rated satisfaction with and importance of 12 care delivery and 18 information and support needs. Unmet need scores (importance minus satisfaction) were estimated. Derived importance scores were assessed by correlating global satisfaction with individual need satisfaction scores. A two-step process for identifying priority areas for improvement was proposed. RESULTS: Patients identified and assigned greater scores to unmet needs for information and support needs (not included in typical satisfaction surveys) compared to typically assessed care delivery needs (p < 0.0001). Direct importance ratings differed substantially from those derived through correlation analyses (r = 0.28, p > 0.3 for care delivery needs and r = 0.17, p > 0.4 for information and support needs). Needs that received high importance and low satisfaction scores were all information and support needs. DISCUSSION: Needs that patients consider very important are usually ignored in typical patient surveys. Derived approaches typically used to assess importance of need from satisfaction data may provide misleading results. If satisfaction surveys are to result in real performance improvement, a fresh examination of the content and importance assessment strategies, as proposed, is needed. PMID- 11221014 TI - Federal efforts to improve quality of care: the Quality Interagency Coordination Task Force (QuIC). AB - FORMATION OF THE QUIC: The Quality Interagency Coordination Task Force (QuIC) was established in 1998 to enable the participating federal agencies to coordinate their activities to study, measure, and improve the quality of care delivered by federal health programs; provide people with information to help them in making more informed choices about their care; and develop the research base and infrastructure needed to improve the health care system, including knowledgeable and empowered workers, well-designed systems of care, and useful information systems. STUDY, MEASURE, AND IMPROVE CARE: The QuIC's initial efforts to improve the care delivered in federal health care programs have focused on diabetes, depression, and the effect of working conditions on quality of care. More recently, patient safety efforts are under way to establish a coordinating center that will enable those who are testing methods of reducing errors to share information across their projects and with experts in error reduction. DEVELOP A RESEARCH BASE AND INFRASTRUCTURE: The QuIC has coordinated efforts in credentialing, information on measures of quality, a taxonomy of quality improvement methods, and errors data collection. PROVIDE INFORMATION TO AMERICANS ABOUT HEALTH CARE QUALITY: The QuIC agencies are developing products that will enhance their ability to communicate with the American people about their health care choices: improved gateways for consumer information available from federal agencies, a glossary of commonly used terms, and guidance for producing report cards on quality of care. MOVING THE QUALITY IMPROVEMENT AGENDA FORWARD: Federal efforts to improve quality of care are moving forward in a more integrated fashion on a wide number of fronts. PMID- 11221015 TI - Irinotecan in small-cell lung cancer: the US experience. AB - There will be approximately 40,000 new cases of small-cell lung cancer this year. Prior to 1990, there were several agents with single-agent response rates of 30% to nearly 90% in the untreated small-cell lung cancer population and approximately 10% to 20% in relapsed patients. During the 1990s, several new chemotherapy agents have displayed activity in small-cell lung cancer (paclitaxel [Taxol], gemcitabine [Gemzar], vinorelbine [Navelbine], topotecan [Hycamtin], and irinotecan [Camptosar, CPT-11]). The majority of studies with irinotecan have been conducted in Japan. The US experience is limited to a single multi institution trial that was conducted in patients with previously treated small cell lung cancer. A total of 44 patients were entered in the study. Patients were stratified by response to prior therapy. Responses occurred in 7 of 44 patients for an overall response rate of 14%. The overall median survival was 4.8 months. PMID- 11221016 TI - Establishment of the standard regimen for non-small-cell lung cancer in Japan. AB - Preclinical data suggest that irinotecan (Camptosar, CPT-11), a novel topoisomerase I inhibitor, has exhibited promising activity in the treatment of lung cancer. In a phase II study of non-small-cell lung cancer, irinotecan demonstrated a 32% response rate. Combinations of irinotecan and cisplatin (Platinol) have also demonstrated synergistic activity against non-small-cell lung cancer. A phase I trial of irinotecan combined with cisplatin in previously untreated non-small-cell lung cancer patients showed an encouraging response rate of 54%, with irinotecan at 60 mg/m2 on days 1, 8, and 15, plus cisplatin at 80 mg/m2. In a phase II study of chemotherapy-naive patients with stage IIIB/IV non small-cell lung cancer, irinotecan/cisplatin yielded a response rate of 52% and a mean survival time of 44 weeks. Data from a phase III trial comparing cisplatin at 80 mg/m2 on day 1 plus vindesine at 3 mg/m2 on days 1, 8, and 15 with two irinotecan-containing regimens--cisplatin at 80 mg/m2 on day 1 plus irinotecan at 60 mg/m2 on days 1, 8, and 15, and single-agent irinotecan at 100 mg/m2 on days 1, 8, and 15--have also been reported. Responses were observed in 32%, 44%, and 21% of patients for the vindesine/cisplatin, irinotecan/cisplatin, and irinotecan arms, respectively, with corresponding median survival times of 45.6, 50.0, and 46.0 weeks; there were no significant differences in response rate or survival between treatment groups for all patients. However, subset analysis of stage IV patients indicated a significant survival advantage for irinotecan/cisplatin; the median survival time was 50 weeks for patients receiving irinotecan/cisplatin, 36.4 weeks for vindesine/cisplatin, and 42.1 weeks for irinotecan (P = .004 for the irinotecan/cisplatin arm vs vindesine/cisplatin; P = .018 for irinotecan vs vindesine/cisplatin). Another phase III study compared irinotecan/cisplatin and vindesine/cisplatin. There was no difference in overall median survival time, and the median survival times were not significantly different for stage IV patients in the respective irinotecan/cisplatin and vindesine/cisplatin arms (44.7 vs 45.3 weeks). Further studies are needed to determine whether irinotecan/cisplatin combinations improve survival in comparison with other promising platinum containing regimens. PMID- 11221017 TI - Treatment of non-small-cell lung cancer in North America: the emerging role of irinotecan. AB - Topoisomerase I inhibitors have demonstrated significant activity in non-small cell lung cancer. In phase II studies, particularly in Japan, single-agent irinotecan (Camptosar, CPT-11) has produced response rates as high as 35%. In combinations with cisplatin (Platinol), it has also resulted in overall response rates of 41% to 52%, with median survival of 10.2 to 13 months, and 1-year survival rates of 33% and 58%. A Japanese phase III randomized trial of irinotecan, either alone or in combination with cisplatin vs vindesine/cisplatin in previously untreated stage IIIB/IV non-small-cell lung cancer, demonstrated that survival among stage IV patients was significantly better in the irinotecan arms compared to the vindesine/cisplatin group. However, another Japanese phase III study comparing irinotecan/cisplatin to vindesine/cisplatin failed to show a survival difference. Initial North American efforts recapitulated this work, while a follow-up study incorporated weekly irinotecan with weekly cisplatin, yielding a response rate of 36%, median survival of 11.6 months, and a 1-year survival rate of 46%. Irinotecan/taxane combinations have also shown promise. Phase I/II studies in advanced non-small-cell lung cancer with paclitaxel (Taxol), irinotecan, and carboplatin (Paraplatin) produced a response rate of 38%, median survival of 11 months, and a 1-year survival rate of 47%; other trials with irinotecan and paclitaxel are ongoing. Phase I data for irinotecan/docetaxel (Taxotere) have indicated an overall response rate of 32%, median survival of 39 weeks, and a 1-year survival rate of 38%; subsequent phase II trials used either cisplatin or irinotecan in combination with docetaxel and yielded a promising median survival of 45.6 weeks, comparable to the standard cisplatin/docetaxel combination. Phase I trials with irinotecan and gemcitabine (Gemzar) have also yielded promising results. Follow-up efforts include phase II studies in both chemonaive advanced non-small-cell lung cancer and progressive small-cell lung cancer (salvage therapy). Clearly, clinical trial data have demonstrated the utility of irinotecan in the treatment of advanced non-small cell lung cancer. Planned combinations with new chemotherapeutic agents and biological response modifiers may provide additional treatment options. PMID- 11221018 TI - Rationale and dose-finding studies of the combination of irinotecan and a taxane on a weekly schedule. AB - Cisplatin (Platinol)-based chemotherapy has been the standard systemic therapy for both non-small-cell and small-cell lung cancer for the past 2 decades, though the efficacy and benefit remain modest. Recently, several novel agents have been introduced that have single-agent activity comparable to cisplatin and offer the possibility of improved therapy for lung cancer. Camptothecin and taxane derivatives are associated with both different mechanisms of action and nonhematologic toxicities, and have demonstrated additive or synergistic activity when used in combination in preclinical studies. We review pertinent clinical studies of these agents in lung cancer and present our experience in combining irinotecan (Camptosar, CPT-11) with taxanes on a weekly schedule in dose-finding and efficacy studies. When chemotherapy is delivered for 4 consecutive weeks followed by a 2-week rest, hematologic toxicity is dose limiting and most prominent during weeks 3 and 4. Dose intensification is feasible if the schedule is modified so the chemotherapy is given on days 1 and 8, with cycles repeated every 3 weeks. The most common nonhematologic toxicities remain asthenia, neuropathy, and diarrhea. Future studies will explore and better define the role of these drug combinations in the treatment of lung cancer. PMID- 11221020 TI - Docetaxel followed by gemcitabine and irinotecan in solid tumors. AB - Docetaxel (Taxotere), gemcitabine (Gemzar), and irinotecan (Camptosar, CPT-11) are active single agents in a variety of solid tumors. In combination, synergism may be schedule dependent. Preclinical studies suggested synergistic interactions when docetaxel was administered 24 hours before gemcitabine or irinotecan. The objective of this phase I trial in patients with refractory solid tumors was to determine the maximum tolerated dose of docetaxel followed 24 hours later by gemcitabine and irinotecan. Two different schedules were tested: docetaxel escalated by 5 mg/m2/cohort from an initial dose of 20 mg/m2 on days 1 and 8 (schedule A) or escalated by 15 mg/m2/cohort from 45 mg/m2 on day 8 only (schedule B). In both schedules, docetaxel was given over 1 hour. Gemcitabine and irinotecan were given on days 2 and 9 (arm A) or 1 and 9 (arm B) at fixed doses of 1,000 mg/m2 over 30 minutes and 100 mg/m2 over 90 minutes, respectively. Escalation of docetaxel was planned in groups of three patients, with three additional patients added at the first indication of dose-limiting toxicity. Four dose levels in arm A and one dose level in arm B have been tested. Seventeen patients were evaluable in arm A; one died of an unrelated cause on cycle 1, and another withdrew consent before beginning treatment. Five of six patients were evaluable in arm B; one patient inadvertently received G-CSF on cycle 1. Forty two cycles have been delivered in arm A (mean; 2.2 cycles/patient), and 25 cycles in arm B (mean, 4.2 cycles/patient); the maximum tolerated dose of docetaxel on arm A was 20 mg/m2. The dose-limiting toxicities were grade 3 diarrhea in one patient, grade 3 infection in two patients, and grade 4 neutropenia for > 4 days in one patient at the 25 mg/m2 level. The dose-limiting toxicities on arm B occurred at the first dose level and included grade 3 diarrhea in one patient, grade 4 diarrhea in one patient, and grade 4 neutropenia for 4 days in another patient. Accrual to schedule B was closed after testing the cohort 1 dose level because testing of a single deescalated docetaxel dose given on day 8 was not considered clinically relevant. PMID- 11221021 TI - Irinotecan: summary and future directions. PMID- 11221019 TI - Irinotecan in combined-modality therapy for locally advanced non-small-cell lung cancer. AB - The management of non-small-cell lung cancer is undergoing rapid evolution. Although the advent of combined-modality therapy has led to improved survival, most patients eventually succumb to the disease. The arrival of a new generation of chemotherapeutic agents--including the taxanes, gemcitabine (Gemzar), and topoisomerase inhibitors such as irinotecan (Camptosar, CPT-11)--offers the hope of advances against this malignancy. Irinotecan, a camptothecin derivative, has shown impressive activity in a variety of solid tumors, including non-small-cell lung cancer. It is believed to act by stabilizing the topoisomerase-DNA complex formed during diverse cellular processes, including replication and transcription. A considerable body of evidence also demonstrates that camptothecin and its derivatives possess substantial radiosensitization properties. This article will review the in vitro and in vivo data on irinotecan's ability to render tumors more susceptible to ionizing radiation. It will then focus on experience with irinotecan and thoracic radiation in the treatment of non-small-cell lung cancer, which has yielded acceptable toxicity results and response rates in excess of 60% in early trials. It is hoped that newer treatment strategies--such as the combination of radiation and irinotecan in lung cancer--will significantly impact cure rates in the future. PMID- 11221022 TI - Current status of irinotecan in lung cancer. AB - Survival in lung cancer patients has not improved over the past 2 decades. Irinotecan (Camptosar, CPT-11), a semisynthetic analog of the quinoline-based alkaloid camptothecin, is one of several new drugs that have demonstrated promising activity in the treatment of lung cancer in recent years. This article gives a brief overview of the mechanism, development history, and current uses of this agent. PMID- 11221023 TI - New state of the art in small-cell lung cancer. AB - Chemotherapy is currently the main treatment for all stages of small-cell lung cancer. In extensive disease, etoposide/cisplatin (Platinol) is standard treatment, and in limited disease, etoposide/cisplatin with early concurrent thoracic radiotherapy twice daily is a typical regimen. Therapeutic outcomes, however, leave substantial room for improvement. The topoisomerase I inhibitor irinotecan (Camptosar, CPT-11) is one of the most active agents against small cell lung cancer. In a phase II study, irinotecan yielded response rates of 33% to 50%, depending on prior treatment status. Combinations with cisplatin have resulted in a median survival of 14.3 months in patients with limited disease and 13.0 months in extensive disease. A phase III study in extensive-disease small cell lung cancer compared irinotecan/cisplatin and standard etoposide/cisplatin regimens, and demonstrated a significant difference in survival in the irinotecan containing arm (411 vs 282 days). Planned phase III studies in North America will confirm and extend these results. Based on these promising data, irinotecan/cisplatin regimens represent a new standard treatment for extensive disease small-cell lung cancer. PMID- 11221024 TI - [Kidney obstruction: potential use of ultrasonography and Doppler color ultrasonography]. AB - Ultrasonography is the first imaging approach in evaluation of patients with urinary obstruction. Presence of hydronephrosis, urinomas and inflammatory complications can be assessed. Moreover, the level and the cause of obstruction are often identified. The major limits of ultrasonography are poor visibility of the lumbar portion of the urinary tract and lack of specificity in detection of pyelocaliectasis. These limits are partially overcome with Doppler studies. Several factors can bias diagnostic accuracy of colour Doppler ultrasonography in evaluating renal obstruction; in particular, partial or intermittent obstruction cause minimum hemodynamic changes in patients with renal colic. Sensitivity of colour Doppler ultrasonography to detect obstruction decreases following medical treatment with NSAID and increases following hydration and diuretics administration. Diuretic ultrasound, colour Doppler evaluation of ureteral jets and evaluation of the twinkling artefact of stones are useful imaging techniques as well. Tissue harmonic imaging is a new imaging technique available in most latest generation US equipments. Evaluation of the kidney and of the urinary tract improves using this technique due to artefact reduction and increased contrast resolution. PMID- 11221025 TI - [Ultrasonography and Doppler color ultrasonography in kidney neoplasms: the demands of the clinician]. AB - The high number of diagnostic methods for images (ultrasound, computer tomography -CT, magnetic nuclear resonance--MNR) has allowed the urologist diagnosis more precocious of renal masses contributing to increase the survival rate and quality of life of patients affected by renal carcinoma. Although many are the advantages that the ultrasound scan gives to the urologist, still today in presence of ultrasound scan results showing expansive renal masses, probably malignant, many perform a CT or MNR for diagnostic confirmation and tumor extension. PMID- 11221026 TI - [Diagnostic approach to newborns with prenatal diagnosis of hydronephrosis]. AB - Prenatal ultrasound examination has radically changed physician's attitude toward hydronephrosis. Fetal hydronephrosis must be searched out and looked at with a wider vision than it was done in the past. A mechanical obstruction must be suspected indeed, but often we have to face a functional dilatation, caused by immaturity, which can clear up in uterus or which will simply require a careful follow-up during the post natal period. Vesicoureteral reflux may count for 10 to 33% of urinary tract dilatations. There are no pathological limit values clearly stated in literature: a pyelectasis can only be the expression of a normal anatomical variability, without features of disease. In creating a diagnostic protocol for the newborn with prenatal diagnosis of hydronephrosis, all these possibilities must be accounted for the risk of focusing on mechanical obstruction is to overestimate and over-treat children that will never obtain any benefit from a surgical procedure. PMID- 11221027 TI - [Fragments of prostatic biopsy: characteristics, dimensions, and number]. AB - Prostate needle biopsy can give important clinical information on tumor extension and grading, useful prognostic parameters for the therapeutic choice and prognostic definition. Currently about the 25% of positive biopsies for carcinoma contain only small foci of cancer that makes histopathological evaluation often the difficult and less reliable. We reviewed the literature about different methods to perform needle biopsies and methods to improve histologic yield of prostatic biopsies in order to obtain more histopathological information on the specimens to improve diagnostic accuracy on core biopsy. We report our initial experience using the preembedding methods proposed by Rogatsch. The best method to perform a prostate biopsy includes the use of using 18-gauges needles, single specimen identification and subsequent orientation of every bioptic fragment by inking its proximal end. We performed the preembedding technique of the fragments, proposed by Rogatsch et al., stretching the fragment between two nylon meshes enclosed in a tissue cassette in formalin. The full length of the biopsy is within the section plane. This technique partially modified in our preliminary experience with the employment of two sponges containing 10% buffered formalin placed in a tissue cassette (2.8 x 3.3 cm). This "sandwich" technique has furnished evident advantages for the pathologist, optimizing the visible area for section plane in comparison to that obtainable from free floating core biopsies. In conclusion, routinely application of the preembedding prostatic core biopsies could improve the accuracy of the histopathological examination and therefore provide more reliable data on tumor extension and grade. PMID- 11221028 TI - [Prostate biopsy: assessment of current indications and techniques]. AB - Following pulmonary carcinoma, prostate cancer in the second leading cause of death due to neoplastic diseases and accounts for approximately 10% of all malignant neoplasms in the european male population. This disease is strictly and age related pathology and as such destined to be increasingly relevant in an ageing general population. The preventive measures and strategies being developed and refined are aimed at diagnosing tumours at an earlier stage and as a consequence increasing life. At this moment in time ultrasound (US) guided transrectal prostate sextant biopsies, described by Hodge as early as 1989, represent the most diffusely employed technique for the diagnosis of prostate cancer. Even if transrectal ultrasound (TRUS) markedly increases the US resolution capacity with respect to those obtainable transperineally or suprapubically, initial enthusiasm associated in performing biopsies of hypoechogenic zones for the diagnosis of early prostate cancers weaned after follow-up studies of this technique became available. Studies from different authors reveal how TRUS is inadequate in precisely pin-pointing prostate cancers above all early ones. According to the data published in the literature between 30 and 57% of hypoechogenic lesions discovered at US are not tumours but rather non-neoplastic prostatic tissue diseases such as acute or chronic infections/inflammations, atrophy, infarcts or prostatic intraepithelial neoplasms (PIN). Furthermore, Chang et al. have shown how sextant biopsies have a greater specificity in diagnosing prostate cancer with respect to single biopsies aimed at hypoechogenic areas, these values being 76 and 50% respectively. Having observed how many repeat prostate biopsies revealed the presence of a prostatic carcinoma following an initial negative prostate biopsy in patients with pre existing elevated prostate specific antigen (PSA) levels has induced many authors to exceed the number samplings, as suggested by Hodge, performed during biopsies. Different diagnostic results obtained by biopsy sampling in different positions and in different numbers (up to a maximum of 18) have recently been compared in different studies. This concept follows the principle that increasing the number of samplings will invariably be associated by an increased diagnostic potential of prostate carcinomas, above all in those "grey zone" patients with PSA values less than 10 ng/ml, thus identifying the prostatic cancer at an earlier stage reducing morbility and correlated mortality, increasing specificity and reducing the quote of unnecessary biopsies. PMID- 11221029 TI - [Alternative for ultrasonographic assessment: role of magnetic resonance with endorectal coil for prostate and seminal vesicle biopsy]. AB - The early enthusiasm for widespread application of magnetic resonance imaging (MRI) with endorectal coil to clinical staging of prostatic cancer has not been substantiated to result in enhanced stage assignment primarily due to the lack of predictive value in the detection of extraprostatic extension. The authors report their experience of this imaging modality both for the evaluation of seminal vesicles invasion and as a guide for rebiopsy in men with suspicious prostate specific antigen (PSA) and a prior negative prostatic mapping. PMID- 11221030 TI - [Digital tridimensional ultrasonography in urology]. AB - Three dimensional ultrasound has gained a firm foothold in the urological field in the last ten years, although it has up to now been used more with scientific and research aims than for clinical and diagnostic purposes. 3D devices can acquire a huge number of images in a very short time (about 4 seconds); the monitor displays the 3 views, of the sagittal, transverse and coronal planes, simultaneously. 3D US can also enable Doppler studies of the arteries and veins and the dedicated software can apply image subtraction techniques, displaying the entire vascular tract cleared of the superimposed images of the other organic systems acquired at the same time. In urology, 3D US devices are most often employed in diseases of the prostate, as the clear view of transition zone on the coronal plane makes it possible to carry out precise guided biopsies, resulting in a proven improvement in early diagnosis of carcinoma in this zone. 3D US can overcome the difficulties left open by conventional TRUS for local staging of cancer. The possibility of following the whole course of the ejaculatory ducts makes it possible to identify any invasion, the first step towards involvement of the seminal vesicles and a negative prognostic factor. The method has also been used in the follow-up of kidney transplant patients. 3D US provides good imaging of the arterial and venous anastomoses and of the course of the vessels down to the smallest ramifications and thus enables more precise assessment of the resistance index, an essential parameter for evaluating rejection. PMID- 11221031 TI - [Tridimensional ultrasonography in andrology]. AB - Three-dimensional ultrasound has already been employed to improve detection and characterization of the masses in various organs. The system can also be expected to improve qualitative evaluation of vessel pathology. Three-dimensional ultrasound could offer an additional contribution even in Andrology, in at least three fields: in the best evaluation of the anatomical structures; in most accurate measurement of the volumes of the organs; in the study of the Peyronie's disease, for the availability of the coronal plain. PMID- 11221032 TI - [Color Doppler and ultrasound-guided prostate biopsy in the diagnosis of prostatic neoplasm]. AB - The diagnosis of prostate neoplasm is still limited today by the variable power of prediction of the three main surveys used: prostate-specific antigen (PSA), digito rectal exploration (DRE) and ultrasound transrectal (TRUS). The study aimed to estimate the benefits and the diagnostic impact of the color Doppler ultrasonography on the diagnosis of prostate neoplasm through biopsies targeted on areas with abnormal flow. With this purpose, 222 biopsies performed on 71 patients between 1997 and 1999 were considered, which led to a diagnosis of neoplasm in 36 patients. Of the 84 biopsies that revealed prostate adenocarcinoma, 74 (64.3%) were correlated to hypoechoic lesions with abnormal flow signals while 41 (35.6%) showed a benign pathology (prostatitis or benign prostatic hyperplasia) (p < 0.0011). In five patients (13%) who did not present any evident lesions at a first transrectal ultrasound, the diagnosis of neoplasm was made only through biopsies targeted on areas with abnormal flow. Therefore, the color Doppler exam can be used during prostate ultrasonography either to consolidate the diagnosis or to give a useful target in case of isoechoic lesions. PMID- 11221033 TI - [Does PSA density of the transition zone represent a useful parameter in the diagnosis of prostate carcinoma?]. AB - Prostate specific antigen (PSA) has unequivocally proved its clinical usefulness ad a serum marker for prostate cancer. In order to enhance the specificity of serum PSA, several diagnostic parameters have been employed including PSA density of transition zone (TZ). The authors report their experience on the efficacy of PSA density TZ with level of PSA < 4 ng/ml, between 4-10 ng/ml, > 10 ng/ml, in the diagnostic of prostate cancer. The PSA density of TZ resulted uscless for PSA levels < 4 ng/ml, but improved the diagnostic specificity associated to PSA serum in the PSA levels ranging between 4-10 ng/ml and > 10 ng/ml. PMID- 11221034 TI - [Validity of PSA density of the transition zone in the diagnosis of prostate cancer]. AB - One hundred four patients (mean age 70.6 years) with prostatic specific antigen (PSA) values between 4 and 10 ng/ml (average 7.9 ng/ml), and with no suspects for neoplasia by digital rectal examination (DRE) and transrectal ultrasound (TRUS) were studied. In all patients PSA density for the entire prostate (PSAD) and PSA density for the transition zone (PSAT) were calculated. TRUS was performed using a 5 MHz probe. Prostate and transition zone volumes were obtained by ellipsoid formula. Aim of the study was to evaluate the PSAT predictivity for prostate cancer compared to the PSAD. Sixteen out of 104 patients (15.4%) had histologically confirmed prostate cancer, and 88 (84.6%) had benign prostatic hyperplasia. When cut-off for PSAD was 0.15 ng/ml/cc, specificity and sensitivity were respectively 75% and 68% with positive and negative predictive values of 54% and 17%; when cut-off for PSAT was 0.34% ng/ml/cc, sensitivity and specificity were respectively 100% and 68% with positive and negative predictive values of 60% and 18%. Our results, according to the literature data, suggest that PSAT seems to have a higher predictivity for prostate cancer than PSAD, providing an optimization for the employ of prostatic biopsy, especially for those patients with PSA values between 4 and 10 ng/ml. PMID- 11221035 TI - [Pelvic ultrasound monitoring of lymphocele in patients treated with radical prostatectomy]. AB - Pelvic lymphoceles, occurred in patients undergone radical retropubic prostatectomy, are believed to increase the risk of deep venous thrombosis and so thromboembolic complications. The authors' aim is to evaluate the usefulness of pelvic ultrasonography in the diagnosis and in the possible early treatment of pelvic lymphoceles. Fifty-eight patients undergone radical prostatectomy and pelvic lymphadenectomy, between January '98 and December '99, underwent a pelvic ultrasonography in VII post-operative day. When a symptomatic or large (over 5 cm) lymphocele was found, it was treated with ultrasound (US) guided drainage. In the study, the following parameters were considered: lymphocele occurrence, size, location and treatment and thromboembolic complication. Statistical analysis was carried out with Fisher's exact test. Pelvic US showed a lymphocele in 23 out of 58 (40%) patients. Mean size was 5 cm. Deep venous thrombosis occurred in 4 patients, all with pelvic lymphoceles. No thromboembolic complications were recorded. In our experience, pelvic ultrasound has shown to be an easy e reliable tool for diagnosis and percutaneous treatment of pelvic lymphoceles. PMID- 11221036 TI - [Repeated ultrasound-guided transrectal prostate biopsy in patients with negative histologic test]. AB - The screening programs for prostate cancer will affect a number increasing of patients over 50 years with consequence rising the bioptic demand. Nevertheless the istopathologic results are negatives for carcinoma in the most part of patients. It's evident that a part of carcinomas are lost at biopsy. Two hundred four patients where submitted at second bioptic session after a maximum of 12 months. Our results show a percent probability of positive findings in 12%. In 75% cancer diagnosed in that second session had clinically significance. Prostate specific antigen (PSA) value, in our study, is the most positive predictive parameter for prostate cancer at second biopsy. Patients with PSA > 10 ng/ml have a risk 7 times greater of having a prostatic cancer respect to patients with PSA < 10 ng/ml. PSA density, PSA velocity and the presence of ipoecoic areas previously biopsied, aren't risk factors for detection of prostate cancer at second bioptic session. PMID- 11221037 TI - [Transrectal ultrasonography in the early diagnosis of prostate carcinoma: use of a new ultrasonography technique with endorectal probe]. AB - Seventy-80% of prostatic carcinoma develops in the peripheral gland. Transrectal ultrasound (TRUS) has the capacity to identify nodules or hypoechogenic areas in the peripheral zone, suspected to be carcinoma. We describe a new echographic technic with endorectal probe (target compression test), to study hypoechogenic areas or nodules in the peripheral gland, during TRUS examination. Thirty-three patients, aged 49-77 years, with prostatic peripheral hypoechoic lesion at transrectal ultrasound, were studied. All patients underwent prostatic biopsy. Ten of the 11 positive patients (non compressible lesion) at the target compression test resulted to be affected by adenocarcinoma. Only 3 of the 22 negative patients (compressible lesion) at the target compression test resulted to be affected by adenocarcinoma. Even if our data have to be confirmed by further studies, they suggest that the target compression test may be a useful complementary test, during TRUS, in the evaluation of hypoechogenic areas in the peripheral gland. PMID- 11221038 TI - [Renal Doppler color ultrasonography in the study of diabetic nephropathy]. AB - The traditional ultrasound approach in the field of diabetic nephropathy provides only partial clinical information; moreover, the data obtained are merely descriptive, in particular regarding the involvement of the intrarenal arteries, which is however the area mainly involved. The aim of our study was to assess the data provided by Doppler ultrasound and in particular the role of the Resistive Index (RI) in a population of 160 type 2 diabetics (NIDDM), divided into 4 groups according to the severity of diabetic nephropathy. The assessment of RI has enabled us to detect among patients in the early stages of diabetic nephropathy (64 patients of group 1), a subgroup of 28 subjects (43.8%) showing RI values equal to or above the threshold value of 0.7. The determination of renal size and of renal parenchyma echogenicity proved to be of little value. The most relevant clinical information is provided by the RI, a parameter that will allow the early detection of patients affected by NIDDM, who show renal vascular involvement without however any other alterations of the traditional ultrasound parameters. PMID- 11221039 TI - [Traditional ultrasonography, directional Doppler power, and levovist in the morphological and functional evaluation of single kidney]. AB - Either the color and the power Doppler have given important information on renal haemodynamics, but these methods are limited. The power directional Doppler (pdD) surpasses such limits; again, administration of Levovist increases the intensity of vascular signal. The aim of this study is the evaluation, in subjects with a solitary kidney, but without evident nephropathies, the morphology, the cortical vascularization and the functional status of the kidney. We studied 21 patients divided into three groups. Group A: subjects with normal renal function; group B: patients with caliceal and pielic dilation; group C: patient with chronic renal failure (CRF). In all subjects, a pdD was effected. Only in three patients it was necessary to administer Levovist, in order to emphasize the parenchymal vascularization. The A group subjects, on echographic B-mode examination, presented a normal morphology and volume of the kidney; on pdD exam, a regular intense and homogeneous parenchymal vascularization, with resistance index (RI) = 0.53 divided by 0.66. In B group, pdD showed an irregular vascularization, with RI > 0.7; also the glomerular filtration rate (GFR) was reduced (70 ml/min). In C group, at the pdD it was relevant a reduced and irregular vascularization in whole renal tissue. If possible, the echographic B-mode examination must be completed with the pdD, with or without Levovist, in order to identify unknown renal pathologies, moreover in subjects with a single kidney. PMID- 11221040 TI - [Incidental kidney neoplasm: anatomopathologic characteristics and clinical behavior]. AB - In the last 20 years, the wide use of abdominal ultrasound and CT scans to diagnose non renal disease has caused an increase in the number of kidney tumours discovered by chance. Our study aimed to compare the anatomopathological features and clinical evolution of kidney tumours discovered incidentally with those of symptomatic kidney tumours. We retrospectively analyzed 338 patients subjected to radical nephrectomy in our Institute between 1979 and 1999, subdivided into two groups: patients with symptomatic tumours vs those with incidentalomas. The following parameters were taken into account: histological type, pathological stage, Furhman's grade and tumour diameter. Finally, overall survival was compared. Of a total of 338 patients, 160 (47.4%), were symptomatic (group 1) and the other 178 (52.6%) had tumours discovered incidentally (group 2), during US in 144 patients (81%), CT in 32 cases (18%), and urography in 2 cases (1%). No significant differences were found as regards the histological type. When the patients were stratified by stage, a greater incidence of tumours in stage T1 was found in group 2 (42.1% vs 29.4%), while advanced forms were more frequent in group 1 (15.6% vs 9%). There were no differences in histological grade between the two subpopulations. The mean size of incidental tumours was 6.1 cm (range: 1.5-20), vs 7.6 cm of symptomatic tumours (range: 2-25 cm). Analysis of overall survival showed a statistically significant difference between the two groups: there were 37 deaths (23.1%) in group 1 vs 24 deaths (13.5%) in group 2 (p < 0.03). Progression of the disease occurred in 47 (29.3%) subjects in group 1 and 41 (23%) in group 2 (p: ns). This study demonstrated significantly longer survival among patients with kidney tumours discovered incidentally. This should be attributed to the lower stage and smaller size of incidentalomas in comparison with symptomatic tumours. PMID- 11221041 TI - [Acquired cystic kidney disease (ACKD): experience of a dialysis center]. AB - Acquired cystic kidney disease (ACKD) is characterized by the substitution of renal parenchyma with multiple cysts in patients either with end stage renal disease who are treated for uremia with dialysis (as on haemodialysis--HD--as on peritoneal dialysis--PD) due to non cystic kidney diseases. The aim of our study was to value the prevalence of ACKD in our haemodialysed patients (with exclusion of polycystic disease and obstructive nephropathy), its relationship between clinical and bioumoral parameters, and its complications in the follow-up. We have studied 56 uremic patients (32f and 24m) on bicarbonate HD three in a week. All our patients underwent renal echography using ECO B mode ALOKA SSD500 with electronic convex sector probe 3.5 MHz for to diagnose ACKD. We divided the population of the study in two groups: the group A includes 23 patients with ACKD; the group B includes 33 patients without ACKD. We analyzed in all patients body mass index (BMI), protein catabolic rate normalized (nPCR), dialitic adequacy index (KT/V), Hb, the serum levels of EPO by ELISA test (MEDAL GmbH, GE, Diagnostika, Hamburg; normal values 5 divided by 30 mUI/ml). We have found a prevalence of 42% for ACKD and statistical significance between the two groups for the duration of HD and BMI (Anova p < 0.01). The EPO serum concentration was higher in the group A (p < 0.05), while their rhuEPO requirement was lower. In two patients of group with ACKD we have found renal carcinoma. In conclusion, by our experience should be opportune to carry out a renal echography at the start of dialysis treatment and every six months for patients with ACKD and every year for those without ACKD. It is necessary to perform the echography of the kidney in all uremic patients before the start of haemo or peritoneal dialysis and report this examination in those patients with ACKD every six months and every year in those without ACKD. PMID- 11221042 TI - [Ultrasonography of the upper urinary tract in patients with spinal cord injury]. AB - A lesion of the upper urinary tract (UUT) is a possible outcome of the bladder dysfunction following a spinal cord injury (SCI). The most common findings are hydronephrosis, bladder-ureteral reflux and pyelonephritis. Aim of the study was to evaluate the prevalence of UUT abnormalities, evaluable by ultrasound (US), in a population of SCI patients; furthermore we correlated the presence of such abnormalities to clinical findings. We evaluated 115 consecutive patients who underwent US scan of UUT. Mean time between injury and our evaluation was 81.5 +/ 100.2 months. Lesion level was cervical (38/115), dorsal (59/115) and lumbar (18/115). Eight patients emptied their bladder spontaneously, 105 by means of intermittent catheterization, while 2 were wearing indwelling catheter. Seventy four patients used anticholinergics drugs. It was evaluated the presence of: hydronephrosis, renal stones and chronic pyelonephritis using US. Afterward the presence of such alterations was correlated to sex and age of patients, time between injury and our evaluation, method of bladder emptying and use of anticholinergics drugs. In 25/115 patients (21.7%) were found abnormalities of UUT. A significative correlation was found between presence of UUT lesions and older age. In our series, prevalence of UUT abnormalities observed by means of US in SCI patients is 21.7%. This finding could be due to correct management and strict follow up of the patients. PMID- 11221043 TI - [Translabial ultrasonography in the diagnosis of stress urinary incontinence in women]. AB - The target of this work is to evaluate the translabial ultrasonography (US) reliability as valid alternative to chain cystography in the pre and post operative assessment of patients with stress urinary incontinence (SUI). From June 1996 to May 1999, we studied 448 patients ranging in age from 35 to 90 years old with SUI from defect of anatomic support. Patients underwent translabial ultrasonography. The translabial US was performed with the patient in lithotomic position using a linear 7.5 MHz probe. The bladder was slightly filled, and the probe positioned longitudinally at the introitus to evaluate downwards and posterior rotation of bladder neck and urethra in basal conditions as well as during the abdominal strain. The evaluation of the anterior urethral angle of the 448 patients who underwent translabial US showed that, during the abdominal strain, all the patients with SUI had a very significative rotation of the urethral axis compared to continent women. Translabial US is a quick, simple, reliable non-invasive procedure. It may be used routinely for the pre and post operative evaluation of anti-incontinence surgery. PMID- 11221044 TI - [Voiding ultrasonographic cystourethrography]. AB - Transvaginal ultrasonography examines the bladder base, the urethral anatomy and the relationship between these structures. This procedure particularly evaluates the striated sphincter and periutrehral structures, during micturition attention is focused on elasticity of urethral walls, deviation of urethral axis, the presence of fibrotic rings, fibrosis extending to the whole urethra and on urethral diverticuli. At che present, the literature available does not provide certain diagnostical criteria for the identification of female vaiding disorders. The high number of proposed therapeutical solutions indicate that the solution to this problem is yet to be found. PMID- 11221045 TI - [Usefulness of ultrasonography in the diagnosis of acute scrotal edema]. AB - Ultrasonography has gained an important role for the diagnosis of acute and chronic scrotal lesions. We report our experience on 6 cases of acute scrotal edema. The etiology of edema was congestive cardiopathy (two patients), glomerulonephrosis (three patients) and lumboaortic lymphnode metastases from bladder transitional cell carcinoma (one patient). Ultrasound scan scrotal appearances were similar in all examined patients, and the only pathologic findings observed were "onion" like appearance and a thickened scrotal wall. Therefore, to define acute scrotal edema etiology, it isn't enough an ultrasound examination, but it's necessary to extend the ultrasound scan assessment to other organs. PMID- 11221046 TI - [Erectile dysfunction: a missed opportunity?]. AB - The increasing of andrological valuation for erectile dysfunction (ED), happened in the last ten years, and induced chemical industries and sanitary system to supply correct answers from cultural, diagnostic and therapeutic views. All these events allowed the people to approach easily to uro-andrological valuations. This situation is perhaps a unique way to involve a great number of men in a wide uro andrological screeening, that is useful, with a total patient and couple involvement, not only for a ED causes research, but also for incidental pathology screening (neoplastic or dismethabolic). Even if more expensive than a simplified diagnostic ED protocol (95% of the patients accept it, if there is a good counseling), this way of diagnostic valuation permit to hit the targets and to add permanently andrology to scientific specialty, as the science that studies the sexuality behaviour of the man and all its pathology. PMID- 11221047 TI - [Unexplained male infertility and testicular microlithiasis]. AB - In this study we analyse the frequency of testicular microlithiasis in a group of otherwise infertile healthy men, visited at the Andrology Service of Prato Hospital. Here the ultrasound machine is located in the ambulatory and it is possible to use it during the first visit of the patient, as we have done in 250 consecutive infertile men. This examination, easy and not invasive, has been performed to evaluate the pampiniform plexus to find possible varicocele, epydidimis for obstructive signs and testes for the presence or absence of parenchymal calcifications or masses. We found 106 positive sonographic records (42.4%) for scrotal diseases. Between them, two cases of testicular microlithiasis (0.8% of 250 consecutive ultrasound examinations and 1.7% in the last twelve months). Our data, although with a lower incidence than literature, show the importance of ultrasound examination in absence of specific diagnostic questions too, in the study of male infertility. Clinical management of testicular microlithiasis is difficult, due to loss of treatment and to cancer risk. A long term follow up is request, with periodical (6-12 months) sonographic controls. A classification (here we propose) can be useful for a more precise monitoring. PMID- 11221048 TI - [Complications of multiple transrectal ultrasound-guided biopsy of the prostate]. AB - The screening programs for prostate cancer will affect a number increasing of patients over 50 years with consequence rising the bioptic demand. For these reason it's important to know the real morbidity correlate with these widespread diagnostic method that will know a larger use in the future. Our study involve 1.467 patients with median age of 66.7 years (range 45-93). Forty-five were diabetics, 80 took a chronic anti-aggregant salicylic therapy, 25 took a chronic coumarolic anticoagulation therapy, 54 had a recent history of prostatitis. Our major complication rate was 0.7% of patients requesting hospital admission and care. An intermediate category of complications was considered, with complication rate of 6.9% and indication for out-patient treatment. Minor complication rate was 76% without need of therapy. In spite of high number of biopsies per patient, our major complication rate is similar of that demonstrate from other authors. In conclusion, whole complication rate is high, but the incidence of major complications is very low. The complications that need out-patient treatment are limited and acceptable. PMID- 11221049 TI - [Ultrasonographic, serologic, and clinical characteristics of a case of prostatic malacoplakia]. AB - An additional case of malakoplakia of the prostate in described to highlight its clinical, echographic and serum features. It's a rarest disease especially when prostate is involved, but well known in world literature. This case is reported to describe more accurately its echographic patterns and also for growing up precision in linguistical expressions used by echographists. We hope to contribute in collecting data about an uncommon pathology. At last we discuss about differential diagnosis when biopsy is negative for neoplasia and how it's possible to end further biopsies. PMID- 11221050 TI - [Ultrasound-guided transrectal biopsy of the prostate]. AB - The author proposes his personal experience through this metodology matured as person in charge of "Modulo di ecografia uro-andrologica ed ecointerventistica", besides a case histories of about 1,000 biopsy exams practiced. PMID- 11221051 TI - [Ultrasound-guided biopsy: screening of prostate cancer with a single set of 14 systematic biopsies]. AB - Standard sextant prostate biopsy may underestimate cancer in men in whom clinical finding and transrectal ultrasound are negative and prostate-specific antigen (PSA) value suspicious for localized prostate cancer (4-10 ng/ml). We describe our experience with a 14 systematic multisite biopsy scheme to detect carcinoma of the prostate (stage T1c). Between January 1999 and February 2000, a total of 177 consecutive patients (mean age 64.1 +/- 7.7 years) underwent systematic transrectal ultrasound (TRUS) guided biopsy for normal digital rectal examination, normal TRUS and abnormal prostate specific antigen 4 ng/ml or greater (4-13 ng/ml). Fourteen core/patient were obtained not depending on prostate size. Biopsies were obtained from conventional sextant biopsies (6 core) and 3 alternate sites which included: the right and left extreme lateral peripheral zone between anterior tissue and posterior gland base (2 core); the right and left transition zone, immediately adjacent to the urethra anterior and posterior (4 core) and the right and left central gland in the mid zone typical of benign prostatic hyperplasia (BPH) (2 core). All specimens were separated for specific location identification. Adenocarcinoma was identified in 61 patients (34.46%). Traditional sextant biopsies showed 23 patients (37.7%) with positive core to detect cancer, while a sextant regimen incorporating lateral peripheral zone biopsies and transitional zone detected 19 cancer (31.1%). The combination of lateral peripheral and transitional zone alone detected cancer in 19 patients. No cancer was detected in central gland. The lateral peripheral zone was the most frequently positive site biopsy with 11 patients (57.9%) followed by the transitional zone with 8 patients (42.1%) in the group of the alternate biopsies sites. Complications of extensive biopsy included hematuria, hematospermia and limited rectal blending in 95% of patients; 1 case of fever (> 38.5 degrees C) for 3 days. Biopsies of the alternate sites are easy, feasible and reproducible. This strategy enhance prostate cancer detection of a 30% compared to conventional sextant biopsies alone. In conclusion, the 6 systematic biopsy of the peripheral zone are inadequate and a minimum of 12 with extensive core in peripheral and transitional zone should routinely be performed to detect a more significant number of men with prostate cancer at stage T1c. PMID- 11221052 TI - [Intraprostatic spread of prostatic carcinoma: stereographic representation based on ultrasonography and biopsy findings]. AB - The aim of this study is to identify and evaluate a scheme of graphic representation of the prostate, that allows the reconstruction of cancer diffusion based on ultrasound findings and on histological biopsy findings. A graphical representation of the prostate using transversal and longitudinal sections is represented by the US-operator, who write severy single performed biopsies (site, directions, and angle) and draws the US relieves. Biopsy specimens are separately prepared on a paper-support and marked at one extremity with china ink. The histopathological examination on every single specimen allows to identify the tumor extent, Gleason grading and the percentage occupied by the neoplasia. Were performed 50 transrectal echo-guided mapping biopsies. Comparing biopsy results with the pathological analysis on 13 whole-mount radical prostatectomy: pathological stage was predicted in 6 of 7 cases, Gleason grading was predicted in 85% of cases. In 5 cases in which the core biopsy histological analysis showed only atypical glands suspicious for cancer it has been possible to repeat new biopsies in the same site of the gland. Tumor was this time diagnosed in 3 of 5 cases (60%). The proposed approach can be useful to reduce variables linked to operator, technique, and single clinical situation, but it needs an employment on a higher number of cases and a verification on more surgical specimens. The scheme proposed has been of easy complication and immediate interpretation by clinicians and pathologists. PMID- 11221053 TI - [Ultrasound-guided cryosurgery of the prostate: short- and long-term experience]. AB - We have assessed 24 patients consecutively treated with cryosurgery and chosen according to the guidelines of the European Study Group of Urologic Cryosurgeons. Of the 24 patients (average age about 70, range 61-79), all were not considered candidates for radical prostatectomy, 9 (37%) were clinical stage cT2 N0M0, 15 (63%) cT3 N0M0 who had not received any prior treatment, except 1 patient (61 years old) who was treated with TCT and successive recurrence of the disease (cT2). Of the 24 chosen patients, 13 (55%) were over the age of 71, 11 (45%) had important factors of co-morbidity and an elevated risk of surgery (ASA 3). The average PSA was of 19.3 ng/ml (range 2.2-61). Gleason score was 2-5 in 9 cases, 6 7 in 14 and 8-10 in 1 case. In the follow-up, we evaluated serum PSA every 3 months and transrectal ultrasound and the echoguided prostatic biopsies at 6, 12 and 24 months. Post-operative complications included: ecchymosis and edema of external genitals (16/24), fever > 38 degrees C (1/24), sloughing syndrome (6/24), urinary tract infections (10/24) acute urine retention (1/24). In 2 cases, 6 months after treatment, a transrectal resection was carried out. After a follow-up at 6 months, the PSA was 0.4 ng/ml (range 0.1-0.9), in 1 case. In positive core biopsy out of 6 showed neoplastic cells with fibrous tissue; the patient had a PSA of 0.58 ng/ml. At 12 months there were 11 assessable patients. The average PSA was 0.3 ng/ml (range 0.1-0.9). At 24 months there were 4 assessable patients, 1 of 4 showed serum PSA level of 4 ng/ml and cancer in apical biopsy. Erectile dysfunction was assessed on 8 patients affective before surgery: 1 referred to sufficient erections at penetration (1/8, 12.5%). After removal of the catheter, 4 of the 20 patients suffered stress and urge incontinence with the use of 1 pad a day. In 1 case, 18 months from surgery, slight stress incontinence was found (1 pad/day). Cryoablation is an efficient method and is given to slight post-operative morbidity and no intra-operative mortality, also in patients with high risk for open surgery. Indications may be found in patients with the following conditions: older than 72 years, severe co morbidity and high risk for surgery, neoplasia at high risk of progression, and disease recurrence after radiotherapy. Our case history is at the moment encouraging and a larger number of cases as well as longer follow-up are needed. PMID- 11221054 TI - [Role of transrectal ultrasonography in the follow-up of patients treated with prostatic cryosurgery]. AB - Cryosurgery of prostate is a minimally invasive treatment for localized cancer. Imaging techniques (transrectal ultrasound (TRUS) or magnetic resonance) have been proposed to evaluate tumor persistence/recurrence after cryosurgical treatment other than serum PSA and prostate biopsies. Actually, criteria to identify cancer after cryosurgical ablation are not well assessed. Aim of this study is to evaluate the clinical significance and role of TRUS in detecting tumor within the former prostate gland after cryoablation. We evaluated ultrasound (US) features and imaging, serum PSA and biopsies in 20 patients treated by cryosurgery at our Hospital with a mean follow-up of 18 months. Twenty patients (mean age 70 years, PSA 25.9 ng/ml, clinical stage: 10 T2 N0M0 and 10 T3 N0M0) were followed up for a mean of 16 months. Ultrasound findings (gland volume, capsule, hypoechoic area, post-voided urine volume, seminal vesicles) were correlated to PSA levels (every 3 months) and prostate biopsies (6, 12 and 24 months). All cases were evaluated by the same ultrasound scanner (Eidos, Hitachi-5-6.5 MHz) and by two operators. Prostate capsule was interrupted by hypo hyperechoic areas in all cases. Transition zone was no more recognizable. Ultrasound findings showed in all cases hypoechoic areas, but US did not identified tumor recurrence in 2 patients. During follow-up, PSA below 0.5 ng/ml was recorded in 75% of cases. We detected tumor in 2 cases, respectively 12 and 18 months after cryosurgery: in the first case few residual cancer cells within fibrous tissue were found in 1 out of 6 biopsies at 6 months (PSA 0.58 ng/ml), in the second one, tumor with viable normal prostatic glands was found in one biopsy of the apex at 18 months (PSA 4.0 ng/ml). TRUS showed several anaechoic foci with necrotic tissue and coalescence of liquid areas in 2 patients (one developed acute urinary retention). Actually, serum PSA is the best marker in order to detect clinically significant tumor after cryosurgery. Hypoechoic areas and capsule interruptions observed by ultrasound imaging of prostate gland after cryosurgery are not correlated with tumor recurrence or tumor persistence. TRUS is only indicated for ultrasound-guided biopsies during follow-up and to confirm urologic complications. PMID- 11221055 TI - [Role of Doppler color ultrasonography in the diagnosis of renovascular abnormalities associated with stenosis of the pyeloureteral junction]. AB - The obstruction of the pielo-ureteral junction, in most of the cases, recognizes an intrinsic etiopathogenesis, the presence of a segment ureteral aperistaltic and alteration of the ureteral musculature. The association of GPU stenosis and the presence of vascular anomalous shanks are frequent. The knowledge of this anatomical situation is important for choosing the therapeutic strategy and the surgical technique. The pre-operative diagnosis of the anomalous vase could condition the choice of the technique (endoscopic technique, laparoscopic), opting for open surgery to have a better control of the vascular shank. We have examined the use of the echo-color Doppler to diagnose the presence of anomalous vase. We have studied 13 patients (6 men and 7 women) between 18 and 62 years of age (average 35 years); the side interested by the obstruction was in 8 cases the right and in 5 cases the left. During surgery in 4 cases out of 13 examined anomalous vases were present. The pre-operative color Doppler found 3 anomalous shanks with a negative false, a positive false and 8 negative trues, showing a sensibility of 75%, a specificity of 88% with a global diagnostic ability of the 84%. We therefore believe that the echo-color Doppler is reliable enough in the pre-operative diagnosis of vascular anomalies associated to stenosis of the GPU and that could be used for pre-operative diagnosis of this urological affection. PMID- 11221056 TI - Non neoplastic diseases of the prostate from transrectal biopsy. AB - Two hundred-seventy-six were screened with one or all diagnostic deviated parameters: neoplastic lesions were 115 (41.7%), non neoplastic were 144 (52.1%), unfit or suspicious were 17 (6.2%). These results are agreed with recent literature and confirm the effectiveness of methodology. PMID- 11221057 TI - [Unusual ultrasonography of scrotal pathology]. AB - The potentialities of ultrasonography in scrotal diseases, with help of color Doppler and angio-power, as well as their sensibility and specificity are discussed presenting three rather rare cases occurred with acute symptoms. It emphasises the utility of emergency scrotal scanning. PMID- 11221058 TI - A renal metastasis from primary peripheral chondrosarcoma presenting as spontaneous retroperitoneal hematoma. AB - The authors describe a case of renal metastasis from chondrosarcoma originating from the rib, with acute clinical onset characterised by serious anaemia secondary to retroperitoneal perineal haemorrhage. No similar cases have been reported in the literature. The interest of this case lies in both the symptoms of onset and in the metastatic site. From a diagnostic point of view an intraoperative ultrasound scan was useful, revealing the presence of a roundish neoformation, irregularly hypogenic, with a different appearance from anything observed by the authors in the other intraoperative ultrasound examinations of renal masses. PMID- 11221059 TI - Permanent brachytherapy: prostate seed implants as an out-patient treatment. AB - Upto April 1999 interstitial seed implants were being performed throughout Europe only as an in-patient treatment. Consequently, we questioned whether this same method could be performed as an out-patient treatment without forfeiting the required quality and safety normally observed with in-patients. Since April 1999 we have treated 73 patients with iodine 125 seed implants (RAPID strand). The average patient age was 65 yrs, the average PSA was 11.5 ng/ml, tumor stage was either T1 or T2. All treatments were carried out in general anesthesia under ultrasound and flouroscopy monitoring. Pre- and post implant dosimetry was planned using the Variplan 6.7 computer program (former MMS). All patients tolerated the out-patient treatment very well. The average duration for anesthesia was 76 minutes, total time per patient spent in the center on implant day was 250 minutes. 54 patients were treated with a monotherapy 145 Gy, while 19 patients received external beam radiotherapy (45 Gy) plus the iodine seed boost (100 Gy). Almost 75% of the patients experienced some form of voiding discomfort during the 4-10th post implant week. In the CT post plan dosimetry performed 4 weeks after the implant, 95% of the patients obtained a good coverage of the prostate with the planned prescription dose. Iodine seed implants can be considered a safe out-patient form of treatment with a low complication and morbidity rate and a high standard of quality. The technical improvements in computer dosimetry software, modified application methods, constantly updated equipment and critical quality assessment has lead to improved overall long term results. PMID- 11221060 TI - Cryosurgical ablation therapy for prostate cancer. AB - Adenocarcinoma of the prostate in the most common malignancy in men and still the leading cause of death from cancer in American men. Current data and published reports indicate that cryotherapy for clinically localized prostate cancer can be an effective treatment method in selective patients. Since 1993, 643 cryosurgical procedures have been performed, including 68 patients who failed radiation therapy, and 20 patients who failed initial cryotherapy. Recently developed targeted cryotherapy techniques, using 6-8 probes, shows promising initial results. The complication rates are also compared favorably to the established therapies for prostate cancer. It is a minimally invasive procedure with a high patient's acceptance rate. It is a highly operator-dependant procedure with a steep learning curve coupled with constantly evolving technology. PMID- 11221061 TI - Patient-reported complications after cryoablation therapy for prostate cancer. AB - To define the patient-reported complications after cryoablation therapy for prostate cancer and to compare these results to previously published patient reported complications for radical prostatectomy and external beam irradiation. A questionnaire similar to previously published patient-reported complication studies was sent to the first 290 patients treated by cryoablation therapy at our Institution. The questionnaire was returned by 267 patients. Forty-four patients were excluded from analysis because of prior irradiation, transurethral prostatectomy, or cryoablation, resulting in a study group of 223 patients. Of the 208 patients with good urinary control preoperatively, 9 (4.3%) patients used incontinence pads after cryoablation. Seven of the 8 patients who used one pad daily reported leakage of only a few drops. Impotency, defined as an inability to obtain erections adequate for vaginal penetration, occurred in 85% of men who were potent preoperatively. Urethrorectal fistula occurred in 1 patient (0.4%). Bladder outlet obstruction caused by stricture of sloughed necrotic prostatic tissue required dilation or transurethral resection in 10% of patients. Scrotal swelling, penile tingling, and pelvic pain occurred in 18, 15, and 12% of patients, respectively; typically, these resolved spontaneously within 3 months. Patient-reported complications for cryoblation compared favorably to those reported for radical prostatectomy and external beam irradiation. Patient satisfaction was high; 96% of patients reported that they would choose cryosurgery as a treatment option again. PMID- 11221062 TI - Local control of prostate cancer by transrectal HIFU-therapy. AB - Transrectal high intensity focused ultrasound (HIFU) as a minimal invasive treatment approach of localized prostate cancer was evaluated concerning its efficacy and security. Post-operative monitoring included PSA-levels and histological results of control random biopsies. Seventy-three HIFU sessions were performed on 62 patients during the period from November 1997 to April 2000. Patients were classified in 4 indication groups: 1) localized prostate cancer, T1 T2, initial PSA < 15 ng/ml, Gleason score < 7, volume < 30 cc, no more than 4 of 6 random biopsies affected by cancer, not suitable for radical prostatectomy; 2) localized prostate cancer, T1-T3, no PSA or Gleason score limitation; 3) local recurrence after first line therapy (RPE, radiation, hormonal ablation); 4) for local debulking. Mean plus or minus standard deviation for patient age was 67.5 +/- 7.48 years, for PSA was 7.64 +/- 5.26 ng/ml and for prostate volume was 21.3 +/- 7.9 cc. Median follow up was 15 months (range 5-29) and included PSA development, control sextant biopsies and transrectal color coded duplex sonography (TCCDS) at 1, 3, 6, 12 and 24 months. At least 1 control biopsy result was available in 48 patients. We evaluated the therapy in 3 categories: 1) group 1 (complete response) included 33/48 patients (68.7%) with no residual cancer and PSA < 4 ng/ml; 2) group 2 (biochemical control) 8/48 patients (16.7%) with small residual cancer and PSA < 4 ng/ml; 3) group 3 (failure) 7/48 patients (14.6%) with residual cancer and PSA > 4 ng/ml (4 of them received hormone therapy). As major complications 2 urethrorectal fistulas occurred, both in post-radiation patients, 3 stress-incontinences II-III after TUR post HIFU. In 20 patients (32.3%) transurethral manoeuvres were necessary to remove obstructive necrotic tissue or because of bladderneck or urethral strictures. 11 of these patients were among the first 20 treated patients. Regarding the individual learning curve about technique, indication and the technical developments HIFU treatment can currently be considered as a valid alternative treatment strategy for patients with localized prostate cancer, who are not suitable for radical surgery. HIFU treatment can be repeated depending on biopsy result and PSA development. Local control of the localized prostate cancer was observed in group 1 and 2 (85%). PMID- 11221063 TI - [Transrectal ultrasound-guided biopsy of the prostate]. AB - The early detection of prostatic neoplasm is nowadays a primary need in the urological field. The availability of transrectal ultrasound equipment alongside with bioptic tools made possible that transrectal ultrasound-guided biopsy of the prostate became the standard procedure to achieve this goal. With this work we would like to confirm the efficacy of this method which is also associated with a good tolerance and low complications rate. 82 patients that came to our Department between 1997 and 1999 were submitted to this procedure, 25 resulted positive for prostatic adenocarcinoma. Only 2 of them did not tolerate the procedure while all the others referred only mild discomfort at the moment of the puncture; 9 patients afterwards had to be admitted to the hospital due to fever (1 patient), acute retention of urine (3 patients) and persistent macroscopic hematuria (5 patients). Transrectal ultrasound-guided biopsy of the prostate reveals to be a safe and accurate method to obtain tissue samples of the prostate along with high tolerance and low incidence of serious complications. PMID- 11221064 TI - [Ultrasound-guided percutaneous nephrostomy]. AB - Percutaneous nephrostomy is a mini-invasive technique that creates an external outlet from the renal excretory tract through a catheter inserted through the flank. Indications for this procedure are of both diagnostic and therapeutic type. The nephrostomic catheter is generally positioned under ultrasound guidance, which has the advantages of showing the localization of the renal cavities and the depth of the kidney, and can be used during pregnancy and in subjects with allergy to contrast medium or with reduced renal function. When possible, it is best to associate US with fluoroscopic guidance, as this association has been found to guarantee a success rate exceeding 98%. Within the kidney, the zone known as Broedel's avascular plane, where the terminal branches of the posterior and anterior arterial systems meet, is the safest place to pass the nephrostomic catheter through, as there is little vascularization in this zone. Access is generally posterior and at the level of the inferior calyx, by means of Seldinger's, the one step or a mixed access technique involving a catheter sheathing a metal cannula. Seldinger's access technique is most commonly used, entailing explorative puncture of the renal cavity with a 22 G needle. We prefer to puncture the kidney direct, under US guidance and using an 18 G needle: a metal wire is passed through the needle and then after withdrawing the needle, the fascia dilators are inserted, of scaled widths increasing up to 2 G wider than the nephrostomic catheter. Care must be taken not to go beyond the curve of the guide wire to avoid trauma to the renal parenchyma. The most critical moment is when the catheter is inserted along the wire at the point of passage through the peri-renal fat: the catheter tends to deflect the point of the guide wire away from the desired direction as the peri-renal fat offers less resistance. The metal wire may be of variable rigidity and length, hydrophilic. The catheter may also be made of various materials: the ideal catheter should slide easily, be flexible, soft and resist encrustation. Each material has its own characteristics but polyurethane is the most ductile and is generally used for nephrostomic catheters. The catheter can also feature different types of point and width and may be autostatic like the Foley catheter or else a cope loop. PMID- 11221065 TI - [Radiofrequency percutaneous ablation in prostatic hypertrophy]. AB - The authors describe both procedure details and results in treating benign prostatic hyperplasia (BPH) by a transcutaneous radiofrequency ablation (TRAP). Using a "cool-tip" needle/electrode, they obtained a large cavitation or a collapse (urethral damage free) of the adenoma, the different result depending on the utilized radiofrequency (RF) energy and the site of application. In this procedure, the US control of the RF effect appears more careful than the "lassic transurethral treatment (TUNA) and it's suitable in prostate's peripheral zone also. The manoeuvre is performed with local or peripheral anaesthesia, is well deobtruent and have not risk of bleeding or other peri-operative complications. PMID- 11221066 TI - [Ultrasonographic study of detrusor thickness in patients with obstruction]. AB - The diagnostic work up of patients with symptomatic benign prostatic hyperplasia is not always useful for diagnosing bladder outlet obstruction, especially if they are compared with pressure-flow studies. The authors make a review of the literature and a clinical study to demonstrate that alternative less invasive methods (ultrasound estimated bladder weight) can often replace pressure/flow studies. PMID- 11221067 TI - [Ultrasonographic assessment of urethrovesical mobility in women]. AB - It is widely accepted that preoperative evaluation of women with stress urinary incontinence should include an assessment of urethrovesical mobility. In the last few decades a variety of methods have been used to this purpose: the so-called Q tip test, radiologic techniques and ultrasonic studies. Transvaginal and perineal ultrasonography allows the assessment of bladder neck and urethral axis mobility at rest, during cough, Valsalva maneuvre and pelvic floor contraction. The technique is simple, not invasive and without discomfort for the patients. Aim of this study is to assess the reproducibility of an ultrasonic technique that allows the measurement of bladder neck mobility (alpha-angle variation) and the angle of the mobile proximal tract of urethra (beta-angle). A total of 58 women were included: 23 with stress incontinence and 35 continent and asymptomatic controls. The technique allows reproducible measurement of alpha and beta angles. In stress incontinent group bladder neck mobility is significantly larger while urethral angle (beta-angle) is significantly smaller and is lowered by straining. PMID- 11221068 TI - [Ultrasonographic study of urethral sphincter in vesico-sphincter dyssynergia]. AB - The ultrasound study of bladder neck and urethral sphincter in men could be performed by means of transrectal ultrasound scan in longitudinal scanning or by probing the surface in transperineal scanning. The endocavitary ultrasound scan study gives the best indications in the evaluation of the bladder neck in men. The neuromuscular bladder dysfunctions' (neurologic bladder), which can be studied by ultrasound scan are dyssinergia, striped detrusor, detrusor-bladder neck dyssinergia, detrusorial iper-reflexy bladder instability. In paraplegic subjects the exam should be performed in gynecological position or in side decubitus, and micturition is obtained by means of sovrapubic percussion and compression or with prevailing action of the abdominal press. The detrusor striped dyssinergia is the dysfunction of the bladder where the ultrasound scan results are more meaningful and give the best elements. In these cases, already in basal conditions, could be present a bladder neck half-opened. During micturition there is an ample opening of the bladder neck and of the prostatic urethra, but scarce relaxation of the membranous urethra; sometimes a protrusion of the back lip of the bladder neck could be present too. In iper-reflexy (unstable bladders) and in detrusorial ipo-reflexy, ultrasound scans could result poorly specific and non-significative. PMID- 11221069 TI - [Normal ultrasonographic anatomy and measurement of the scrotum]. AB - In this study we reported scrotal ultrasound examination findings and their clinical applications. We describe the normal ultrasound structure patterns, the size measurements and the imaging findings about each anatomic part of male's gonadal gland: scrotal sac, testis, epididymys, spermatic funiculus. PMID- 11221070 TI - [Ultrasonography in the prediction of sperm presence in the epididymis]. AB - Azoospermia represents approximately 10% of case of male infertility. Identification of etiological aspects is very important for prognostic and therapeutic evaluation. After the testicular analysis with fine needle aspiration cytology (FNAC) we reviewed the scrotal sonograms of 639 azoospermic patients. In the group of patients with obstructive azoospermia we have found a particular sonographic appearance. This consisted in a normal aspect of the testis, the epididymis have an enlargement, development of cysts and an inhomogeneous echo pattern. However we have found this particular sonographic appearance in same patients with other kinds of azoospermia. In conclusion, scrotal sonogram is a fundamental step in the diagnostic work-up of the azoospermic patient, but it does not allow to distinguish unequivocally patients affected by obstructive azoospermia. PMID- 11221071 TI - [Minimally invasive treatment of intraprostatic cysts]. AB - Prostatic cysts are rare; they are to be considered in the evaluation of obstructive azoospermia. A correct diagnosis is based on transrectal ultrasound of the prostate. Herein we describe our experience with perineal ultrasound cyst aspiration. During the last 10 years, 21 infertile patients underwent ultrasound puncture of an intraprostatic cyst. Patients were placed in the lithotomy position, a 16 G needle was adopted; by means of ultrasound was possible to follow the needle entering the cyst. The content was aspirated and, if no spermatozoa were detected in the cystic liquid, sclerosing agents were introduced. The technique was performed successfully in all patients with symptomatic cyst within the prostate. Follow-up prostatic ultrasound and semen analysis were performed in 17 patients. There was 1 recurrence that was aspirated again. In 12 cases an increase in sperms number and motility was obtained, in 3 cases oligoastenospermia remained unchanged and 2 patients are still azoospermic. In 3 cases the partners become pregnant. PMID- 11221072 TI - [Doppler color ultrasonography in the diagnosis of erectile dysfunction of vascular origin]. AB - The aim of this paper is to evaluate whether echo-color Doppler diagnostics allows to detect the different evolutionary stages of arteriopathy affecting the cavernous arteries of the penis. 124 patients with erectile deficiency were examined. All of them were evaluated by andrologic and psychologic anamnesis. An echo-color Doppler examination was performed on cavernous arteries before (basal) and after (dynamic) an injection of Prostaglandin E1 (10 micrograms). The penile circulation has been observed for twenty minutes after the injection to detect anomalous collateral vessels of the cavernous arteries. The population was divided into 4 groups according to the basal and dynamic peak systolic velocity (PSV). Cardiovascular risk factor incidence in patients with normal basal and dynamic PSV values (group A) and in patients with pathologic basal and dynamic PSV values (group C) is 10% and 44% respectively (p < 0.002). Psychologic disorder in group A and C is 41% and 26% respectively (p < 0.05). Patients with pathologic basal PSV and normal dynamic PSV (group B) show an intermediate (26%) incidence of cardiovascular disorders as compared to A and C. Anomalous side branches are equally represented in A and B (41% and 38%) and to a lesser extent in C (26%). Based on anamnestic and instrumental data, Group B ranges at an intermediate position between A and C. In this group, the presence of incipient arteriopathy affecting the penile circulation may be suspected. The ability to detect patients with vascular diseases still at a subclinical stage, as it already happens for other organs, would allow a prompt therapeutic action. PMID- 11221073 TI - [Doppler color ultrasonography of the normal penis]. AB - The penile blood vessels arise from the internal pudendal artery. After the arcuate ligament the artery is usually called the main penile artery. Afterwards the vessel is divided into the dorsal penile artery, which is thin, and the cavernosal artery, which enter the corpus cavernosum on the supero-medial surface of the penis. The branches of this artery are called the arteriae helicinas that subsequently divide in smaller vessels that communicate with the lacunae of the corpus cavernosum. The venous blood flow is drained into the venous plexus beneath the tunica albuginea. The emissary veins perforate the albuginea and the blood is drained by the venae circumflexae into the deep dorsal vein. Color Doppler sonography allows actually to depict all these vessels and to study the blood flow in these structures with the exclusion of the lacunar spaces. To detect slow flows the technical parameters are very important and the Doppler angle must be always less than 60 degrees. During pharmacologically induced erection the peak systolic velocity in the cavernosal artery shows different values, according to the time of measurements. Initially high systolic velocity is detected (over 35 cm/s) and high diastolic flow (8-15 cm/s) due to low intracavernosal resistance. After veno-occlusive mechanism activation, an increase of flow is normally observed with peak systolic velocity up to 80-120 cm/s associated to progressive decrease of diastolic flow. In the initial phase of the erection the venous flow is characterized with elevated blood velocity in the circumflex and deep dorsal veins. Afterwards with progressive erection the venous flow reduces to disappear completely with full rigidity. Three dimensional US allows a better visualization of the morphology, number and distribution of the vascular tree of the penis. PMID- 11221074 TI - [Doppler color ultrasonography in patients with erectile dysfunction]. AB - The introduction of new oral therapy doesn't change the rule of color Doppler US in the screening modality of the diagnosis of vasculogenic impotence. The hemodynamic changes can be non invasively evaluated with color and energy Doppler US and with spectral analysis following injection of a vaso-active pharmacological agent. The new high sensitive US equipment allows an easy detection of the cavernous artery. Duplex Doppler can quantify the systolic diastolic flow changes after the intra-cavernous vaso-active drugs injection. It is then possible to establish the diagnosis of arterial or venous vasculogenic impotence. The organic cause can also be excluded. The pick systolic velocity less than 0.30 m/sec is indicative of arterial origin. The absence of flow reversal in the diastolic phase, 30 minutes after the injection, is significant for a venous type problem. Elicine arteries can be visualised and analysed using high sensitive color Doppler energy US equipment. PMID- 11221075 TI - [Ultrasonographic study of Peyronie's disease]. AB - Induratio penis plastica (IPP) is a degenerative disease, which consists in a thickening of the albuginea tunica of cavernous corpora, especially on the dorsal aspect. In 25% of the cases a calcified deposit is present. This disease can determine a bending of the penis, usually upward, pain during erection and impotentia coeundi. It is associated with Dupuytren's disease in 25% of the cases. IPP is of unknown etiological origin. The more reliable etiological theories are the degenerative one (micro trauma and inflammation) and the autoimmune one. The assessment of IPP is based on story, physical examination, autophotography (which are necessary) and on imaging techniques such as ultrasound, color Doppler, CT, MRI and X-ray in mammography. Color Doppler has demonstrated to be the best technique because of its cost/benefit and cost/effectiveness ratio. RMI with gadolinium can determine plaques activity but it has a lower cost/benefit ratio. Color Doppler can determine the presence of an IPP plaque and its status, which is size, location, and degree of calcification. Some authors sustain that inflammation can be suggested by the presence of micro vascularization around the plaque. US can be very useful to detect plaque in a size not easily accessible by physical examination (on the dorsal aspect of the penis) and to demonstrate plaques in different evolution moment. Ultrasonography is the better technique to show directly albuginea tunica. Authors illustrate the methodology, which use intra-cavernous injection of prostaglandin E1 (PGE1) to induce erection and its semeiotic findings. PMID- 11221076 TI - [Ultrasound-guided ESWT in Peyronie's disease plaques]. AB - The aim of the study was to check the efficiency of shock waves in the treatment of Peyronie's disease. The instrument, because of its lithotriptic power, already used in the treatment of orthopedic disease and salivary stones, can be used to break plaques in induratio penis plastica. A total of 481 patients affected with Peyronie's disease were entered into a prospective trial. Patients with big plaques or with an initial stage of degeneration were excluded. We divided the patients into three treatment groups: a) shock waves alone in 56 patients; b) a combination of shock waves and calcioantagonist (perilesional injection) in 324 patients; c) calcioantagonist alone in 101 patients. The group of 101 patients (group C) treated during the previous 2 years with a medical therapy based only on the injection of calcioantagonist, was used as a control group. Ultrasound evaluation of the treated plaques showed a reduction of size in 27/56 patients of the group A, in 159/324 patients of the group B and in 39/101 patients of group C. Painful erection improved in the 91.5% of group B, against the 45.7% of group C. Furthermore, we pointed out, with interviews to the patients, a considerable improvement of the pain and of the sexual performances. The therapeutic association of shock waves with calcioantagonist injections is an effective non operative treatment for the stabilization of Peyronie's disease. PMID- 11221077 TI - [Peyronie's disease: ultrasonographic follow-up of ESWT]. AB - The application of a small-sized lithotriptor for the extracorporeal shock-wave treatment (ESWT) of La Peyronie's disease (PD) was originally suggested by Butz, in 1996. In November 1996 we started to use this method with the aim of checking its tolerability and effectiveness. From April 1998, we standardized our protocol treatment as follow: higher treatment frequency: each every other day; higher energy density value: at least level "4" (= 0.11 mJ/sqmm). From March 1998 to May 2000, 82 patients with PD, aged between 44 and 74 (average age 53.8) were treated according to this protocol. A case history was drafted for each patient and they all underwent an objective examination, a dynamic ultrasonic scan of the penis and a photograph of the penis after drug-induced erection. The complaint had lasted for a period of time varying from a minimum of 3 to a maximum of 120 months (average time 23.3 months). 44 patients reported painful erections and 78 patients showed bending of the penis during erection. The pre-treatment dynamic ultrasonic scan of the penis revealed plaques with calcific features in 36 patients, while for the remaining 46 cases the ultrasonic images were compatible with fibrotic thickening. On completion of the 4th treatment session, the patients were given a questionnaire to fill in so that we could obtain a subjective evaluation of the results achieved. All the patients underwent photograph and dynamic ultrasonic scan of the penis (both performed after drug induced erection, pre- and post treatment). Slight alteration often appeared on the skin of the penis (petechias), which disappeared spontaneously within 48 hours. On completion of the 4th treatment session, 37 patients out of 82 (45%) reported subjective improvement described as "stoppage" in the progression and/or partial regression of the disease" with a filling of a saller size of the plaque on-self examination. As far as concerns pain, this symptom disappeared in 31 out of the 44 patients concerned (70.4%). At the clinical check, based on the ultrasonic scans carried out after ESWT, in 34 cases of 82 (41%), it was possible to note a reduction in the echogenicity or in the size of the treated plaque. In 32 patients (39%) an unchanged plaque was observed, and in 16 case a larger plaque or a calcific evolution was established. For what the bending of the penis concerns, the comparison between the photographs revealed a reduction of the curvature in 24 patients out of 78 (30.7%). Of the 46 patients in whom the disease had non-calcific characteristics, according to the ultrasonic scans, 21 (46%) showed improved disease since in 25 (54%) the treated plaque had stabilized or worsened. In the group of 36 patients with the calcific plaques, 13 (36%) improved while 23 (64%) resulted unchanged or worsened. PMID- 11221078 TI - [Efficacy of bacteriophages in complex treatment of patients with burn wounds]. AB - Results of clinical and laboratory evaluation of the treatment with pyobacteriophage in tablets of the patients with burn wounds are presented. It was shown that phagotherapy provided more rapid cure of pyoseptic complications, temperature normalization, wounds purification and lower lethality Bacteriological analysis of wound secretions revealed that after the treatment staphylococci and streptococci were cultured 2 times rarely, Proteus spp. Were isolated 1.5 times rarely, E. coli was not isolated. The amount of positive haemocultures also diminished. Investigation of immunologic status demonstrated statistically significant normalization of immunity on cell level. Phagocytosis level didn't change while in control group (without bacteriophage use) it became lower. Antibody level enhanced but less extensively than in control group. The results of trial demonstrates positive effect of phagotherapy use at the patients with burns. PMID- 11221079 TI - [Comparative antibiotic susceptibility in vitro of microbial isolates from patients with complications after gastrectomy for stomach carcinoma and from contents of their large intestine]. AB - Antibiotic susceptibility of the main isolates from the large intestine contents and pathological substrates of 12 patients after gastroectomy for stomach carcinoma was studied. Three of them developed esophagoenterostomy incompetence, 4 had intraabdominal abscesses and in 5 infection of the operation wound was stated. In all, 30 isolates of enterobacteria, 28 isolates of enterococci and 38 isolates of bacteroides were tested. Antibiotic susceptibility of the isolates from various sources was practically identical, which showed that before surgical operations for stomach carcinoma it was necessary that data on the patients intestine microbiocenosis and antibioticograms of the main isolates should be available to correct severe dysbiotic disorders. PMID- 11221080 TI - [Risk factors of fatal outcome in community-acquired pneumonia]. PMID- 11221081 TI - [Pneumonia caused by Chlamydophila (Chlamydia) pneumoniae: clinical data, diagnosis, and therapy]. PMID- 11221082 TI - [Cephalosporin antibiotics: the first ones by their significance and complexity of their discovery]. PMID- 11221083 TI - [Tamoxifen in prophylaxis of breast cancer]. PMID- 11221084 TI - [Current problems in etiotropic therapy of mycoses]. PMID- 11221085 TI - [Oxadin effect on actinomycetes strains]. AB - The results of research show that oxadin has mutagenous effect on the tested actinomyces strains, in particular on Streptomyces albus--producer of the polyether antibiotic salinomycin. The colonies grown up after spores treatment with oxadin, have been tested for auxotrophy, morphological mutations and biosynthesis of the antibiotic salinomycin. Treatment of Streptomyces albus strain with 10% oxadin for 10 or 20 min provided the isolation of highly active strains. Dispersion analysis data revealed statistically significant differences between the control (non treated) and the oxadin-treated Streptomyces albus populations. PMID- 11221086 TI - Single lesion paucibacillary leprosy: baseline profile of the Brazilian Multicenter Cohort Study. AB - In Brazil, there is little information about the clinical and epidemiological characteristics of paucibacillary, single skin lesion leprosy patients (SSL-PB). Only recently has the official notification system distinguished leprosy patients with a single lesion as a clinical entity, for whom the single-dose ROM (rifampin, ofloxacin and minocycline) regimen has been recommended. In this paper, we describe the baseline clinical features and the immunological background of a multicenter cohort of SSL-PB leprosy cases enrolled between December 1997-1998. Patients were recruited at health centers located in the following regions: Southeast = Rio de Janeiro; North = Amazon and Rondonia states and Center-West = Goias state. Eligible cases were newly detected, untreated single-lesion leprosy patients without thickened nerve involvement, and were assessed by clinical, bacilloscopic and histopathological exams. The Mitsuda skin test and anti-PGL-I serology (ELISA) were also performed. Of the 299 SSL-PB leprosy patients, 259 (86.6%) fulfilled the criteria for single-dose ROM intervention. Our results showed that patients recruited from different sites had similar features, considering the clinical and immunological profiles. There was a predominance of adults (mean age 32.4; S.D. = 16.0), and a BCG scar was detected in 76.7% of the children (< or = 15 years old). Only 7 cases were diagnosed as the multibacillary type, representing less than 3% of the patients being misclassified. Our data indicate that in Brazil SSL-PB case ascertainment based on clinical and bacilloscopic criteria can be accurately defined under a routine control program; 75.0% of SSL-PB cases were Mitsuda positive (> or = 5 mm) and seropositivity for anti-PGL-I was detected in 17.3% of the patients. These data are compatible with effective cell-mediated immunity and low bacillary load, suggesting favorable clinical outcomes for most SSL-PB participants of this cohort. PMID- 11221087 TI - Leydig cell hyperplasia and the maintenance of bone volume: bone histomorphometry and testicular histopathology in 29 male leprosy autopsy cases. AB - This study was conducted to determine if osteoporosis in male leprosy patients is caused by testicular atrophy. Bone volume (BV/TV), trabecular number (TbN), trabecular thickness (TbTh), and trabecular separation (TbSp) were measured in two areas in decalcified paraffin sections of lumbar bones from 29 male leprosy and 6 male nonleprosy autopsy cases. We found significant differences in the average BV/TV measurements among the 7 patients with nodular Leydig cell hyperplasia (BV/TV 12.24%) and the 22 patients without hyperplasia (BV/TV 7.35%) and 6 patients without leprosy (BV/TV 12.98%). Bone volume was maintained in patients with nodular Leydig cell hyperplasia, and we determined no clinical factor other than the Leydig cell hyperplasia that reflected the bone volume. The osteoporosis of male leprosy patients was attributed to secondary gonadal dysfunction due to testicular atrophy, and Leydig cell hyperplasia appears to preserve bone volume. PMID- 11221088 TI - Histoid, a clinical variant of multibacillary leprosy: report from so-called nonendemic areas. AB - This is a hospital-based study of 25 biopsy-proven cases of histoid leprosy in the arid, northwest Rajasthan region of India. Over an 11-year span, a total of 893 new cases of leprosy were diagnosed at our institution. These 25 histoid cases thus make up 2.8% of our new patients. Various clinical and laboratory observations are summarized and compared to other published series. PMID- 11221089 TI - Relapse as histoid leprosy after receiving multidrug therapy (MDT); a report of three cases. AB - The histoid type of leprosy has been described as occurring in lepromatous leprosy patients who relapse after many years of apparently successful dapsone monotherapy. Three patients who had received the World Health Organization recommended regimens of multidrug therapy (WHO/MDT) relapsed as histoid leprosy 12-15 years after completion of treatment. In one patient, through mouse foot pad studies, the bacilli were found to be sensitive to rifampin and clofazimine and resistant to dapsone. In the other two patients mouse foot pad studies were inconclusive. The patients were re-started on WHO/MDT. Two patients took regular treatment and improved, both clinically and bacteriologically. One patient was irregular in treatment, and 1 year after re-starting WHO/MDT nodules were still present although the bacterial index had fallen slightly. PMID- 11221090 TI - Serious side effects of rifampin on the course of WHO/MDT: a case report. AB - A male born in 1935 was diagnosed as having lepromatous leprosy when he was 17 years old. In addition to dapsone (DDS) monotherapy, he had been treated with rifampin (RMP) for 2 terms: first with 450 mg a day for 2 years when he was 39 years old; second with 150 mg a day for 2 months after a 1-year interval from the first regimen. During these entire courses with RMP, no complication was noted. When he was 64 years old in 1999, a diagnosis of relapsed borderline tuberculoid (BT) leprosy was made, and he was started on the multibacillary (MB) regimen of the World Health Organization multidrug therapy (WHO/MDT). After the third dose of monthly RMP, he developed a flu-like syndrome and went into shock. A few hours later, intravascular hemolysis occurred followed by acute renal failure. He was placed on hemodialysis for 7 series and recovered almost completely about 2 months later. The immune complexes with anti-RMP antibody followed by complement binding may have accounted for these symptoms. Twenty-four reported cases of leprosy who had developed side effects of RMP under an intermittent regimen were analyzed; 9 of the cases had had prior treatment with RMP but 15 had not. Adverse effects were more likely to occur in MB cases and were more frequent during the first 6 doses of intermittent regimens. The cases with prior treatment with RMP had had a higher incidence of serious complications such as marked hypotension, hemolysis and acute renal failure. However, many exceptions were also found, and we could not verify any fully dependable factor(s) to predict the side effects of RMP. More field investigation is desirable, and monthly administration of RMP must be conducted under direct observation through the course of WHO/MDT. PMID- 11221091 TI - Efficacy of single-dose ROM therapy plus low-dose convit vaccine as an adjuvant for treatment of paucibacillary leprosy patients with a single skin lesion. AB - The recent World Health Organization multicentric field study on the treatment of paucibacillary (PB) leprosy patients with single skin lesion (SSL) and a single dose of rifampin-ofloxacin-minocycline (ROM) brought new hope to those who are engaged in the eradication of leprosy from India. Being encouraged by the WHO report, we undertook the present hospital-based study and found that PB leprosy patients with SSL were morphologically and histopathologically heterogeneous. The histological spectrum of SSL ranged from indeterminate through tuberculoid (TT) to borderline tuberculoid (BT) leprosy, and most patients had active BT leprosy. Ninety new, untreated PB leprosy patients with SSL were included in the present study for comparative assessment of the efficacies of ROM and ROM plus Convit vaccine therapies. Children, pregnant women, lactating mothers and patients with any thickening of nerves were excluded. All patients were bacteriologically negative (skin-smear test) but lepromin reactive. The patients were divided into two groups after proper matching for morphological and histological status of SSL: a) The test group included 60 patients and the control group included 30 patients. The test group was given a single dose of ROM initially and two injections of low-dose Convit vaccine, one initially and the other at the end of 3 months. b) The control group was given only a single dose of ROM initially. Both groups were followed clinically every 2 weeks for 6 months and retested for histological, bacteriological and lepromin status at the end of 6 months. Thereafter, they were followed clinically every month for another 6 months. In the test group, the SSL resolved in 33.3%, regressed in 48.3%, and remained active in 18.3% of the patients, while the granuloma disappeared in 70% of the cases. Only one patient developed neuritis, and in another patient the disease relapsed on the eighth month. On the other hand, the SSL in the control patients resolved, regressed and remained active in 13.3%, 63.3% and 23.3% of the cases, respectively, while the granuloma disappeared in 53.3% of the cases. In the seven patients who remained active, the disease course was progressive, and two of them developed neuritis. The clinical outcome of the patients treated with ROM plus low-dose Convit vaccine was statistically superior to those treated with single dose ROM therapy alone. PMID- 11221092 TI - Sensory testing with monofilaments in Hansen's disease and normal control subjects. AB - Sensory testing with Semmes-Weinstein filaments was conducted on: 112 normal subjects to determine the effects of age, gender and occupation on threshold perception, 27 Hansen's disease (HD) patients to determine inter-observer and intra-observer reliability of testing, and 101 patients with HD and a history of hand and/or foot ulceration to identify thresholds for injury risk. Filament thresholds were found related to age (p < 0.002) and occupation (p < 0.001) but not gender (p > 0.1). Inter-observer and intra-observer reliability was found to be high (intraclass correlation coefficient = 0.88-0.93). The 4.93 (7.0-7.7 g) filament had 97% sensitivity and 100% specificity for identifying a history of foot injuries, and the 4.17 (1.2-1.6 g) filament had 100% sensitivity and 100% specificity for identifying hand injuries. PMID- 11221093 TI - Knowledge and attitude of health professionals in relation to the integration of leprosy control into the general health service in Ethiopia. AB - Since the introduction of multidrug therapy for leprosy patients, the integration of leprosy control in the general health service (GHS) system has been an issue of debate. In Ethiopia, the present policy stresses integrated management of diseases. In spite of the policy, however, leprosy control was a vertical program until 1998 in most parts of the country. A descriptive cross-section study was conducted in the southern region of Ethiopia from October 1996 to March 1997 to determine the levels of involvement of the GHS staff and to identify obstacles to their involvement in the management of leprosy patients. Through a written questionnaire, data were collected from 240 GHS staff, including doctors, nurses and health assistants. It was found that 6% of the GHS staff was involved in leprosy control activities, mainly case finding and health education. Negative attitudes toward leprosy workers were held by 13% of the GHS staff while 40% had intermediate attitudes and the remaining 47% had positive attitudes. Statistically significant differences were found with regard to the level of knowledge among different health professionals, type of health institutions and years of service. The levels of involvement, knowledge and attitude of GHS staff showed that lack of integration and training were core problems. Hence, policy makers should give due attention to promoting the involvement of the GHS staff by integrating the program into the GHS system using the approach already in place in certain parts of the country. PMID- 11221095 TI - Leprosy at a turning point? PMID- 11221094 TI - Hansen's disease in a patient with a history of sarcoidosis. AB - We report a rare case of concomitant Hansen's disease (HD) and sarcoidosis. Reticulin staining may be a helpful diagnostic tool in establishing the diagnosis of sarcoidosis in skin lesions. The diagnosis of HD can be established despite negative polymerase chain reaction results for the detection of Mycobacterium leprae DNA. Finally, a well-established diagnosis of sarcoidosis does not preclude the development of another granulomatous disorder. Hence, when new lesions developed in a patient with sarcoidosis despite appropriate therapy, other concurrent diagnoses should be pursued. PMID- 11221096 TI - Development of TT leprosy in a BCG-vaccinated individual: immunological response during disease and after spontaneous healing. PMID- 11221097 TI - Dapsone drug resistance in the MDT era. PMID- 11221098 TI - Tumor necrosis factor promoter polymorphism (TNF2) seems to protect against development of severe forms of leprosy in a pilot study in Brazilian patients. PMID- 11221099 TI - Single-dose treatment for single lesion leprosy; histopathological observations. PMID- 11221101 TI - A simple splint. PMID- 11221100 TI - Childhood leprosy in Chandigarh; clinico-histopathological correlation. PMID- 11221102 TI - [Past, present and future of occupational medicine]. AB - The author retraces development of occupational pathology as an important part of general pathology in Russian Federation. The article covers priority directions in occupational pathology research to preserve and improve workers' health in Russia. PMID- 11221103 TI - [The state of free-radical oxidation in workers engaged in oil-processing industry]. AB - The author represent evaluation of free-radical oxidation in RBC, serum and urine among workers engaged into pyromellitic dianhydride. Individuals contacting chemical pollutants during pyromellitic dianhydride production de monstrate significant changes in free-radical oxidation parameters of RBC, serum and urine. PMID- 11221104 TI - [Berlition R 300 oral -- alpha-lipoic acid preparation for the correction of body changes associated with high serum iron content]. AB - Medication Berlition 300 oral, produced by "Berlin-Hemie", induces lower serum iron content, decrease in transferrin content of whole blood and serum proportionally to increased urinary iron excretion and lower serum bilirubin and normalizes serum glucose level. Berlition 300 oral, lipoic acid preparation made by "Berlin-He mie" (Menarini group), could be recommended for treatment of high serum iron content and iron overload, especially in association with diabetes mellitus. PMID- 11221105 TI - [Features of respiratory diseases in ecologically unfavorable region]. AB - Examination of 400 workers in Bratsk aluminium plant proved respiratory diseases formation to be influenced by both occupational factors and various toxic chemicals that are released into atmosphere by other industrial polluters. Structure of respiratory diseases is represented mainly by diffuse pneumoconiosis caused by toxic and dust factors. Prophylaxis of those diseases should be aimed not only to better work conditions, but also to specify measures improving regional ecologic situation. PMID- 11221106 TI - [Combined effects caused by chronic exposure to vinyl chloride and dichloroethane]. AB - The authors studied solitary and combined effects of vinyl chloride and dichloroethane in chronic (4 months) inhalation experiment using concentrations of 50 and 500 mg/m3. The experiment revealed general toxic effects including disorders of central nervous system and liver. Those disorders are caused by reductive-oxidative reactions disturbances and dystrophic processes. The authors determined safe combinations of vinyl chloride and dichloroethane concentrations for associated action. PMID- 11221107 TI - [Carcinogenic danger of nickel and its compounds (review of literature)]. PMID- 11221108 TI - [Improving the system of medical examinations in individuals working with occupational hazards nowadays]. AB - To solve the problem of medical examinations system improvement according to Russian Federation Health Ministry Order No. 90, the Department for Occupational Hygiene Supervision specified several directions: -cooperation with medical commissions of health care facilities and with occupational safety divisions at industrial enterprises to determine contingents and volume of further research; - organization of conferences in municipal health care department with representatives of health care facilities and employers; - cooperation with specialists in public hygiene and occupational center for complex inspection of health care facilities; - preparation of information for and participation for and participation in interdepartmental commission conference based on clinical expert commission in occupational pathology center and in municipal department on work safety; - cooperation with occupational pathology center in activities of license committee. PMID- 11221109 TI - [On the evaluation of gene toxicity and mutagenicity of mullite refractories]. PMID- 11221110 TI - [Experience in treatment of chronic toxic hepatitis by ursodeoxicholic acid]. PMID- 11221111 TI - Steps and strategies. PMID- 11221112 TI - Developing qualitative databases for multiple users. AB - Conventionally, anthropological data are collected and analyzed by individuals, and although researchers may use data managers to organize their information, there is little need to classify and code systems to be accessible to others. Recently, however, qualitative and quantitative data have been collected in projects with multiple researchers. Difficulties with the establishment, verification, and management of databases for multiple users, particularly in longitudinal studies, are considerable if the rules underlying coding schemes are difficult to identify or if the documentation is cumbersome. Drawing on the authors' experiences in Australia, the use of computer packages for data management is discussed, and the importance of preserving the integrity of data and maintaining context while facilitating its continued and varied use is emphasized. PMID- 11221113 TI - When the visit to the emergency department is medically nonurgent: provider ideologies and patient advice. AB - It is estimated that more than half of pediatric hospital emergency department (ED) visits are medically nonurgent. Anecdotal impressions suggest that ED providers castigate medically nonurgent visits, yet studies on such visits are scarce. This study explored the perspectives of 26 providers working in the EDs of two urban hospitals regarding medically nonurgent pediatric ED visits and advising parents or guardians on appropriate ED use. Three provider ideologies regarding the appropriateness of medically nonurgent ED use were identified and found to be linked to particular communication strategies that providers employed with ED users: restrictive, pragmatic, and all-inclusive. The analysis resulted in the development of a typology of provider ideological orientations toward ED use, distinguished according to different orientations toward professional dominance. PMID- 11221114 TI - Reflections on validity and epistemology in a study of working relations between deaf and hearing professionals. AB - In this article, a research study that examined the working relationships between Deaf and hearing professionals in health and educational services in the United Kingdom is addressed. These service providers worked in bilingual organizations where both British Sign Language and English were used and in which Deaf people's identity as a cultural-linguistic minority was accepted. The focus of this article is on issues of validity and epistemology that arose for the Deaf and hearing research team in the course of this study. In particular, it examines the influence of identity attributions on the research process for researchers operating within a context of historical oppression, minority language use and legitimization of research knowledge, and challenges to the interpretative analysis used in the study that arose from the dynamics of majority-minority power relations in the wider social world. PMID- 11221115 TI - Empowerment and Australian community health nurses' work with aboriginal clients: the sociopolitical context. AB - A portion of a study designed to explore community health nurses' (CHNs) perceptions of the concept of empowerment in their work with Australian Aboriginal clients is discussed in this article. The 12 study participants were identified through purposive convenience sampling. During this exploration, contentions regarding the concept of empowerment emerged, revealing the sociopolitical context of CHN's work with Aboriginal people that shaped their practice in crucial ways. These issues emerged from the participants' discussions regarding the meaning of empowerment in their work with Aboriginal clients and the strategies for and challenges to working in empowering ways within the context of Aboriginal health. Selected components of Habermas's works provided a useful framework to facilitate an understanding of the forces that underpin community health nursing practice. PMID- 11221116 TI - Team collaboration: a case study of an early intervention team. AB - The study described in this article sought to examine the workings of an interdisciplinary team as a research entity and as a service provider. There were two levels of analysis in the study: the process of collaborating on the research and the results of the research observation of an interdisciplinary team in a clinical setting. An interdisciplinary research team studied the interaction of a single clinical team over a 6-month period working with one child in a hospital based early intervention program. The data were collected through intensive interviews, direct observations of the family and team members, and selected videotaping of team meetings. Qualitative data analysis methods were used, and five themes emerged: who takes the lead, the classroom as a way station, we like our freedom but..., who is giving and who is taking advice, and communication comes in few forms. PMID- 11221117 TI - Moving them on and in: the process of searching for and selecting an aged care facility. AB - This exploratory, descriptive study examined the search and selection process for an aged care facility following discharge of a family member from an acute setting. Few studies have examined this process and its effects on families. Individuals from 25 families where a family member had been recently admitted to an aged care facility following discharge from an acute setting were interviewed. This article reports participants' perceptions of the search and selection process and its effect on the family. Five major themes emerged from the data: good fortune, wear and tear on the sponsor, dealing with the system, urgency, and adjusting. The results can be used to inform and assist families and health professionals working with families in this situation. PMID- 11221118 TI - Low-income African American adolescents who avoid pregnancy: tough girls who rewrite negative scripts. AB - The purpose of this research was to generate a grounded theory that explains the social-psychological processes of low-income African American adolescents who avoided pregnancy. Data collection included focus groups and in-depth interviews with 17 women aged 19 to 26. Data analysis using the grounded theory method revealed that these girls were the recipients of negative social-psychological scripts, putting them at risk for poverty and early childbearing. The "tough girls" struggled to rewrite these scripts by recognizing their negativity, being disenchanted with the scripts, determining to be different, and creating better lives. These aware, introspective young women believed in self-responsibility, self-protection, education, and financial independence. Practice implications and considerations for programmatic interventions can be based on this analysis. PMID- 11221119 TI - Enhancing the rigor of grounded theory: incorporating reflexivity and relationality. AB - Some proponents of the grounded theory method appear to treat interview and participant observation data as though they mirror informants' realities. Others claim that grounded theory incorporates reflexivity. It is claimed in this article that the principal texts on grounded theory do not attend to the effects of interactions between researchers and participants in interview and participant observation contexts. Descriptions of the effects of interactions on interview data and attention to relationships between interviewers and interviewees are necessary for attending to the rigor of grounded theory findings. Therefore, it is argued that reflexivity and relationality, which are defined as attending to the effects of researcher-participant interactions on the construction of data and to power and trust relationships between researchers and participants, should be incorporated into grounded theory. PMID- 11221120 TI - Engaging with phenomenology: is it more of a challenge than it needs to be? AB - When seeking to understand the human condition, with all the problems this enterprise poses for traditional scientific research approaches, qualitative research is held to be in some ways superior to rigidly quantitative research. As a result, many beginning health researchers plan to employ a qualitative approach to explore topics that were previously inaccessible via traditional scientific means. However, implementing a qualitative approach is not an easy process and, in many cases, researchers must look long and hard to find material to assist them in developing their research plans. This may be particularly so in phenomenological research. This article examines some of the problems and pitfalls faced by phenomenological researchers new to the approach. Through accounts of personal experience, it highlights some of the areas where phenomenological researchers could be helpful by being less reticent about the process of implementing a phenomenological study. PMID- 11221121 TI - Patterns of sexual mixing: mechanisms for or limits to the spread of STIs? PMID- 11221123 TI - Operational performance of an STD control programme in Mwanza Region, Tanzania. AB - OBJECTIVES: To describe important details of the design and operational features of the Mwanza sexually transmitted diseases (STD) control programme. To assess the feasibility of the intervention, the distribution of STD syndromes observed, the clinical effectiveness of syndromic STD case management, the utilisation of STD services by the population, and the quality of syndromic STD services delivered at rural health units. METHODS: The intervention was integrated into rural primary healthcare (PHC) units. It comprised improved STD case management using the syndromic approach, facilitated by a regional programme office which ensured the training of health workers, a reliable supply of effective drugs, and regular support supervision. Five studies were performed to evaluate operational performance: (i) a survey of register books to collect data on patients presenting with STDs and reproductive tract infections (RTIs) to rural health units with improved STD services, (ii) a survey of register books from health units in communities without improved services, (iii) a survey of register books from referral clinics, (iv) a home based cross sectional study of STD patients who did not return to the intervention health units for follow up, (v) a cross sectional survey of reported STD treatment seeking behaviour in a random cohort of 8845 adults served by rural health units. RESULTS: During the 2 years of the Mwanza trial, 12,895 STD syndromes were treated at the 25 intervention health units. The most common syndromes were urethral discharge (67%) and genital ulcers (26%) in men and vaginal discharge (50%), lower abdominal tenderness (33%), and genital ulcers (13%) in women. Clinical treatment effectiveness was high in patients from whom complete follow up data were available, reaching between 81% and 98% after first line treatment and 97%-99% after first, second, and third line treatment. Only 26% of patients referred to higher levels of health care had presented to their referral institutions. During the trial period, data from the cohort showed that 12.8% of men and 8.6% of women in the intervention communities experienced at least one STD syndrome. Based on various approaches, utilisation of the improved health units by symptomatic STD patients in these communities was estimated at between 50% and 75%. During the first 6 months of intervention attendance at intervention units increased by 53%. Thereafter, the average attendance rate was about 25% higher than in comparison communities. Home visits to 367 non-returners revealed that 89% had been free of symptoms after treatment, but 28% became symptomatic again within 3 months of treatment. 100% of these patients reported that they had received treatment, but only 74% had been examined, only 57% had been given health education, and only 30% were offered condoms. Patients did not fully recall which treatment they had been given, but possibly only 63% had been treated exactly according to guidelines. CONCLUSIONS: This study demonstrated that it is feasible to integrate effective STD services into the existing PHC structure of a developing country. Improved services attract more patients, but additional educational efforts are needed to further improve treatment seeking behaviour. Furthermore, clear treatment guidelines, a reliable drug supply system, and regular supervision are critical. All efforts should be made to treat patients on the spot, without delay, as referral to higher levels of care led to a high number of dropouts. The syndromic approach to STD control should be supported by at least one reference clinic and laboratory per country to ensure monitoring of prevalent aetiologies, of the development of bacterial resistance, and of the effectiveness of the syndromic algorithms in use. PMID- 11221124 TI - Vaginal yeasts in the era of "over the counter" antifungals. AB - OBJECTIVE: To establish whether there has been any rise in the prevalence of non albicans Candida species isolated from vaginal swabs since the introduction of "over the counter" antifungal treatments. METHOD: A retrospective review looking at all positive vaginal yeast isolates collected from women attending one genitourinary medicine clinic during the 6 year period from 1993 to 1998 inclusive. All positive vaginal yeast isolates were included, regardless of whether or not the patients were symptomatic. Isolates from HIV positive women were excluded from the analysis. RESULTS: No increase in non-albicans vaginal yeast isolates was shown during the period studied. The proportion of non albicans yeasts remained constant at approximately 5% of the total yeasts isolated. The most common non-albicans yeast isolated was C glabrata. CONCLUSION: There is no evidence from this study to suggest that the increasing use of "over the counter" antifungal treatment has selected for atypical, possibly inherently azole resistant, strains of vaginal yeasts in HIV seronegative women. PMID- 11221125 TI - Syndromic management of urethral discharge in Ghanaian pharmacies. AB - OBJECTIVES: To evaluate the training of pharmacists in Accra, Ghana, in the syndromic management of STIs. METHODS: We randomly selected 50 pharmacy outlets that had received the training (intervention) and 50 outlets that had not received the training (no intervention). Simulated clients described the symptoms of urethral discharge to the first pharmacy staff encountered and completed a standardised questionnaire after each encounter. RESULTS: Correct drug provision for urethral discharge improved with the educational intervention but remained relatively low (no intervention 18%; intervention 39%; p < 0.05). More encouraging, treatment for gonorrhoea was usually correct without the intervention (64%) and improved further in the intervention outlets (76%). The treatment for chlamydia was less often appropriate but also improved (31% and 41%). Condom promotion was poor, with almost no outlets offering condoms. CONCLUSIONS: The current training led to improvements in the treatment of urethral discharge. Future training needs to be improved, especially with regard to condom promotion. Moreover, since less than one third of simulated clients were seen by pharmacists, the training should be expanded to other pharmacy staff. With enhanced training of all pharmacy staff, the role of pharmacy outlets in STI management and prevention in Ghana and elsewhere can be optimised. PMID- 11221126 TI - Cerebrospinal fluid tau concentrations in HIV infected patients with suspected neurological disease. AB - OBJECTIVES: To measure cerebrospinal fluid (CSF) tau in HIV infected patients with acute neurological episodes and to correlate the findings with the type and severity of neurological disease. METHODS: CSF tau was prospectively measured in 76 consecutive HIV infected patients admitted to a specialist unit at UCL Hospitals, London, for investigation of acute neurological episodes: the results were compared with the clinical diagnoses. RESULTS: 24 patients had HIV associated dementia complex (HADC), 10 had lymphoma (including four with primary CNS lymphoma), 20 had cerebral infections (including five with CMV encephalitis, five with VZV infection, seven with cryptococcal meningitis, two with toxoplasmosis, and one with progressive multifocal leucoencephalopathy); 22 patients had miscellaneous conditions, including nine with self limiting headache/fever. 62 patients (82%) had normal CSF tau concentration and 14 patients (18%) had elevated tau. In those with HADC, there was no correlation between the degree of dementia or atrophy on magnetic resonance imaging and CSF tau. Elevated CSF tau was associated with poor outcome as six of eight patients who died within 4 weeks of lumbar puncture had elevated tau (p = 0.0024, two tailed Fisher's exact test). CONCLUSIONS: CSF tau levels are not elevated in the majority of HIV infected patients presenting with acute neurological episodes. CSF tau levels show no correlation with severity of dementia/atrophy on magnetic resonance imaging. Although elevated CSF tau was observed in some patients with conditions causing cerebral necrosis, the finding did not delineate underlying pathology but was associated with poor outcome. PMID- 11221127 TI - STI prevention and the male sex industry in London: evaluating a pilot peer education programme. AB - OBJECTIVE: To evaluate the effectiveness of a pilot peer education STI prevention programme with male sex workers. DESIGN: A process and outcome evaluation of the pilot programme undertaken in three London male escort agencies, using a quasi experimental design. SUBJECTS: Workers in three London escort agencies, including 88 who completed a questionnaire, five peer educators, and a further 16 men (including management) working in two of these agencies. METHODS: A peer education STI prevention programme run by the Working Men Project (WMP), a specialist sexual health service for male sex workers, was piloted in two London escort agencies. Five male sex workers participated in a 2 day peer education training programme. They then returned to their respective agencies to disseminate information and condoms, in an attempt to influence norms of behaviour. An outcome evaluation aimed to assess changes in STI related knowledge, high risk sexual behaviour, and attendance at a sexual health service. A pre-intervention questionnaire assessing variables such as STI related knowledge, sexual behaviour, and demographic information was administered in both agency A and agency B and a third agency, C, which acted as a control. Ten weeks after the peer educators returned to their agencies, the same questionnaire was administered in the same agencies. Peer educator referrals to the WMP were also recorded over this time period. The process evaluation involved interviews and focus groups with peer educators, and the completion of diaries about their experiences in the role. A further 16 men working in the agencies (including managers and an owner) were interviewed about their experience of the programme. Participant observation was also undertaken through regular outreach work to the agencies. RESULTS: 57 men completed the questionnaire at time 1 and 44 at time 2. Unfortunately, only 13 of these were matched, precluding any meaningful analysis of change in STI related knowledge and sexual behaviour. The questionnaire provided a profile of the men working in the agencies. Of the 88 men who completed the questionnaire at least once, the majority were homosexual, and in their late teens/early 20s. Most were of a "white" ethnic group, though there was some range within these categories. Most preferred to speak English and education levels were high. Relative STI knowledge revealed a high understanding of HIV and hepatitis B, moderate understanding of gonorrhoea, syphilis, genital warts and herpes, and little knowledge of non-specific urethritis (NSU) or chlamydia. Sexual behaviour suggested a highly sexually active population with both male and female paying and non-paying partners. Condom use was highest for paying partners, particularly for anal sex. Condom use for oral sex with all partners was less consistent, and condom use for all types of sex with regular partners was lower than with other partners. The small number of men engaging in vaginal sex with paying and regular partners were less likely to use condoms. 26 new patients registered at the WMP as a result of peer educator referrals, representing 65% of all new contacts over the study period. The process evaluation revealed that while the training programme was considered adequate and while peer educators felt the programme and their roles to be a success, their experience of the role was difficult. The role of management support was crucial in supporting the programme. The assumption that "peers" are particularly effective educators was not borne out by the results. While peers were considered suitable to discuss some aspects of the industry, many preferred to consult "professionals" about health related matters. The concept of "peers" was problematic with most of the men drawing "peers" from subgroups within the agencies. Other constraints on behaviour such as a lack of power, particularly with regard to a lack of management support, or poverty, had a substantial impact on behaviour which were not influenced by the peer educators. CONCLUSIONS: The study illustrated the difficulties of utilising quasi-experimental evaluation methodology with this client group. It also demonstrated the limitations of peer education based on information provision health education models which focus on individual behaviour change. Suggestions are given for future interventions. PMID- 11221128 TI - Baseline STD prevalence in a community intervention trial of the female condom in Kenya. AB - OBJECTIVE: We present baseline sexually transmitted disease (STD) prevalence rates from an ongoing intervention trial at Kenyan agricultural sites. METHODS: After gaining the cooperation of management, we identified six matched pairs of tea, coffee, and flower plantations and enrolled approximately 160 women at each site. Six intervention sites received an information programme and distributed female and male condoms, while six control sites received male condoms only and similar information about them. At clinic visits, we tested participants for cervical gonorrhoea (GC) and Chlamydia trachomatis (CT) by ligase chain reaction on urine specimens, and Trichomonas vaginalis (TV) by culture. The study has 80% power to detect a 10% prevalence difference during follow up, assuming a combined STD prevalence of 20%, 25% loss to follow up and intracluster correlation coefficient (ICC) of 0.03. RESULTS: Participants at intervention and control sites (total 1929) were similar at baseline. Mean age was 33 years, the majority were married, more than half currently used family planning, 78% had never used male condoms, and 9% reported more than one sexual partner in the 3 months before the study. Prevalences of GC, CT, and TV were 2.6%, 3.2%, and 20.4% respectively (23.9% overall), and were similar at intervention and control sites. The ICC for STD prevalence was 0.0011. Baseline STD was associated with unmarried status, non use of family planning, alcohol use, and more than one recent sexual partner, but the highest odds ratio was 1.5. CONCLUSIONS: Baseline results confirm a high prevalence of trichomoniasis and bacterial STD at these Kenyan rural sites. Improved STD management is urgently needed there. Our ongoing female condom intervention trial is feasible as designed. PMID- 11221129 TI - The association between abuse in childhood and STD/HIV risk behaviours in female genitourinary (GU) clinic attendees. AB - OBJECTIVES: To compare and contrast women with a history of child abuse with those who have no history of child abuse on STI/HIV risk behaviours and safer sex beliefs in an inner city UK sample. DESIGN: Cross sectional sample survey. METHODS: Routine female clinic attendees were invited to complete an anonymous self report questionnaire which included background information, sexual and drug risk behaviour, self reported sexually transmitted infections (STIs), psychological distress (Hospital and Anxiety Depression Scale; HADS), Sexual Risk Cognitions Questionnaire (SRCQ), and history of child sexual, physical, and emotional abuse. RESULTS: 137 (45%) of 303 women reported a history of child abuse; all three forms of child abuse--sexual (26%), physical (20%), and emotional (27%) abuse--overlapped. The majority of women reported one sexual partner in the past month, and the majority did not use condoms. Women reporting a history of child abuse were more likely to have had previous STIs (p = 0.007) and to have had more than one STI (p = 0.04) compared with women who had not experienced child abuse. Injecting drug use and commercial sex work were of low prevalence across the whole sample and no group differences were found. Women reporting a history of child abuse had higher HADS anxiety (p = 0.03) compared with women with no history of child abuse. Confidence in using condoms with a sexual partner was not related to child abuse. Women with a history of child abuse reported significantly higher frequency of thoughts reflecting anticipated negative reactions from partners to suggesting condom use (p = 0.02) and judging a partner's risk by their appearance (p = 0.05) compared with women with no history of child abuse. CONCLUSIONS: Comparable rates of child sexual abuse with US studies were found in this UK inner city population of women attending sexual health services. Women who had experienced child abuse were more likely to report ever having had an STI and having had more than one STI. Complex psychological and social factors contribute to difficulties for women in negotiating safer sex including emotional distress, abuse histories, and anticipating a negative reaction from partners. Multifaceted prevention models are needed. PMID- 11221130 TI - Predictors of syphilis seroreactivity and prevalence of HIV among street recruited injection drug users in Los Angeles County, 1994-6. AB - OBJECTIVES: To describe HIV prevalence and the association between syphilis incidence and sexual and drug injection risk behaviours in a cohort of street recruited injecting drug users (IDUs) in Los Angeles County, between 1994 and 1996. METHODS: During the study period, 513 street recruited African-American and Latino IDUs were screened for syphilis and antibodies to HIV. Subjects were administered a risk behaviour survey at baseline and followed up at 6 month intervals for 18 months with repeated interviews and serological screening. Rate ratios were used to examine associations between syphilis incidence and demographic characteristics and risk behaviours. A proportional hazard model was used to identify predictors of syphilis incidence independent of demographic characteristics. RESULTS: 74% of the sample were male, 70% African-American, 30% Latino; and the median age was 43 years. Overall baseline serological prevalence of HIV was 2.5% and of syphilis 5.7%. None of the participants were co-infected for HIV and syphilis at baseline or at any of the 6 month follow ups. Among 390 eligible IDUs retained for analysis of incidence data, the overall syphilis incidence was 26.0 per 1000 person years. Higher syphilis incidence was found for women compared with men (RR = 2.70; 95% CI 1.60, 4.55), and for those 44 years of age or younger compared with those 45 years of age and older (RR = 2.26; 95% CI 1.25, 4.08). African-Americans were more likely to be syphilis incident cases when compared with Latinos, although the difference did not reach statistical significance (RR = 1.27; 95% CI 0.72, 2.23). In bivariate analysis, risk behaviours significantly associated with higher syphilis incidence included injection of cocaine, "speedball" and heroin, "crack" smoking, recency of first injection event, backloading of syringes, injecting with others, exchanging drugs or money for sex, multiple sex partners, and non-heterosexual sexual preference. Variables that significantly predicted syphilis infection at follow up in the multivariate analysis included multiple sex partners (RR = 7.8; 95% CI 2.4, 25.0), exchanging money for sex (RR = 3.0; 95% CI 0.9, 9.6), and recent initiation to injection drug use (RR = 4.6; 95% CI 1.1, 18.8). CONCLUSION: Syphilis transmission among IDUs in Los Angeles County remains a serious public health concern, particularly among IDUs who engage in trading of sex for money or drugs. Although low, the prevalence of HIV observed in this study constitutes a serious concern because of the potential for expanded HIV transmission in this susceptible population of IDUs with high syphilis incidence. Enhanced case finding screening efforts and prevention of transmission of sexually transmitted infections should specifically target hard to reach IDUs and their sexual partners. PMID- 11221131 TI - Assessment of risk for pelvic inflammatory disease in an urban sexual health population. AB - OBJECTIVES: To determine the sexual and demographic risk factors for the acquisition of presumptive pelvic inflammatory disease (PID). METHODS: A retrospective, case-control study in women, who attended the Sydney Sexual Health Centre (SSHC), between April 1991 and December 1997. Logistic regression analysis was used to adjust for confounding variables. RESULTS: 741 women with PID and an equal number of controls were included. Cases were significantly younger than controls (p < 0.001). 42% of cases were born in north or South East Asia, compared with 12% of the controls (p < 0.001). The adjusted odds ratio for being born in north or South East Asia was 2.8 (95% CI 1.70-4.46), for not speaking English at home was 1.6 (95% CI 1.02-2.55), for having had previous PID was 5.9 (95% CI 3.59-9.73), and for being employed in the commercial sex industry and being born in north or South East Asia was 2.8 (95% CI 1.22-6.22). Women aged 15 19 were at considerable risk of developing PID (OR 5.3 (95% CI 2.76-10.11)). Women with previous human papillomavirus infection were significantly less likely to develop PID (OR 0.6 (95% CI 0.42-0.79)). The use of IUCDs (OR 4.5 (95% CI 2.14 9.39)), condoms (OR 1.4 (95% CI 1.03-1.87)), and not using contraception (OR 1.8 (95% CI 1.20-2.76)) was each associated with an increased risk. CONCLUSIONS: Several measures may help to reduce the burden of PID. Women should be encouraged to delay the onset of sexual activity and IUCDs should not be used in young women. Sexual health services for women whose home language is not English, and for commercial sex workers born in north or South East Asia should be improved. PMID- 11221132 TI - Circumcision and STD in the United States: cross sectional and cohort analyses. AB - BACKGROUND: Male circumcision status has been shown to be associated with sexually transmitted disease (STD) acquisition in some, but not all, studies. Most studies have been cross sectional. OBJECTIVES: We examined the association between circumcision status and the prevalence and incidence of gonorrhoea, chlamydia, and syphilis. METHODS: We analysed cross sectional and cohort study data from a multicentre controlled trial in the United States. Between July 1993 and September 1996, 2021 men visiting public inner city STD clinics in the United States were examined by a clinician at enrolment and 1456 were examined at follow up visits 6 and 12 months later. At each visit, men had laboratory tests for gonorrhoea, chlamydia, and syphilis and were examined for circumcision status. We used multiple logistic regression to compare STD risk among circumcised and uncircumcised men adjusted for potentially confounding factors. RESULTS: Uncircumcised men were significantly more likely than circumcised men to have gonorrhoea in the multivariate analyses, adjusted for age, race, and site, in both the cross sectional (odds ratio (OR), 1.3; 95% confidence interval (CI), 0.9 to 1.7) and in the cohort analysis (OR, 1.6; 95% CI, 1.0 to 2.6). There was no association between lack of circumcision and chlamydia in either the cross sectional (OR, 1.0; 95% CI 0.7-1.4) or the cohort analysis (OR, 0.9; 95% CI 0.5 1.5). The magnitude of association between lack of circumcision and syphilis was similar in the cross sectional (OR, 1.4; 95% CI 0.6 to 3.3) and cohort analysis (OR, 1.5; 95% CI 0.4 to 6.1). CONCLUSION: Uncircumcised men in the United States may be at increased risk for gonorrhoea and syphilis, but chlamydia risk appears similar in circumcised and uncircumcised men. Our results suggest that risk estimates from cross sectional studies would be similar to cohort findings. PMID- 11221133 TI - Preliminary safety and acceptability of a carrageenan gel for possible use as a vaginal microbicide. AB - OBJECTIVE: We sought to determine the safety and acceptability of vaginal gel formulation PC-503 among low risk, abstinent women. The active ingredient was 2% pharmaceutical grade lambda carrageenan, a sulphated polymer that is generally recognised as safe by the US Food and Drug Administration. METHODS: 35 women in five sites applied 5 ml of the PC-503 gel vaginally once a day for 7 days while abstaining from sexual intercourse. Visual vaginal examinations were performed on days 1, 4, and 8. STI testing and vaginal pool Gram stain preparations were done on days 1 and 8. Participants were asked about product acceptability. RESULTS: 34 of the 35 women enrolled completed 7 days' use. Following product use, five reported mild symptoms including "bladder fullness," "genital warmth," or discomfort, and lower abdominal pain, and one had moderate pale yellow cervical discharge. Using the Nugent criteria, three women had bacterial vaginosis (BV) before and after use; three had BV before but not after, and two had BV after but not before. Most of the women found PC-503 to be pleasant or neutral in feel and smell and considered extra lubrication to be an advantage; however, one third found it to be messy. CONCLUSIONS: Vaginal use of PC-503 gel did not cause significant adverse effects in a small number of low risk, sexually abstinent women. Further testing in larger numbers of sexually active women is planned. A smaller volume of gel may be more acceptable to some women. PMID- 11221135 TI - The management of Chlamydia trachomatis: combined community and hospital study. PMID- 11221134 TI - Helicobacter pylori infection transmitted sexually via oral-genital contact: a hypothetical model. AB - OBJECTIVES: To postulate that Helicobacter pylori infection may be transmitted sexually, using the human female vagina as a reservoir for transmission. METHODS: A literature search was performed using Medline, Embase, Biological Abstracts, and Currents Contents (January 1983 to August 2000). Relevant keywords were used and additional manual searches were made using the reference lists from the selected articles to retrieve other papers relevant to the topic. CONCLUSIONS: Helicobacter pylori infection could be transmitted sexually with the vagina acting as a potential temporary/permanent reservoir given the right environmental conditions. PMID- 11221136 TI - Retrospective study of male lichen sclerosus and outcome in Leicester: 1995-9 inclusive: experience of a genitourinary medicine clinic. PMID- 11221137 TI - Chaperoning male patients. PMID- 11221138 TI - Ciprofloxacin 250 mg for treating gonococcal urethritis and cervicitis. PMID- 11221139 TI - Investigation of the increased incidence of gonorrhoea diagnosed in GUM clinics in England, in 1994-6. PMID- 11221140 TI - Perceptions of disease and therapy are factors influencing adherence to antiretroviral therapy. PMID- 11221141 TI - The power of information and contraceptive choice in a family planning setting in Mexico. PMID- 11221142 TI - AIDS and globalisation. PMID- 11221143 TI - WSW status needs further definition. PMID- 11221144 TI - The role of the lecturer in the preceptor model of clinical teaching. AB - Preceptorship models of clinical teaching are becoming increasingly popular in undergraduate nursing education. According to the literature the role of the lecturer is very unclear in this model of clinical teaching. This article reports on a descriptive study undertaken within a school of nursing where the author was formerly employed. The study explored the role of the lecturer. The findings demonstrate the educational orientation of the lecturer role and also highlight the tension that continues to exist between the world of education and the world of practice. PMID- 11221145 TI - Creating a child abuse policy that reflects an ethic of care. AB - The primary purpose of child abuse policy is to guide the action of health care providers and so ensure that the fundamental rights of those the policy intended to protect are not compromised. This discussion paper explores the ethical considerations underlying child abuse policy from bioethical and from caring ethical perspectives, both of which are outlined briefly. A process that could be used to create or analyse existing child abuse policy, in relation to underlying ethical considerations, definitions of child abuse, level of health care, resourcing needs and relationship to employment policy is outlined. A hypothetical example of such a policy is used to illustrate elements of this process. Assuming that policy is designed to direct action, it is argued that if child abuse policies were rewritten to reflect an ethic of care the quality and scope of health care provided to children and their families would improve. Consequently, stated government objectives of improving child health services, as well as primary health care aims of achieving equitable, accessible and affordable health care for children in New Zealand would be better facilitated. PMID- 11221146 TI - Negotiating the ethical minefield of psychiatric nursing practice. AB - Psychiatric nursing practice can be likened to an ethical minefield. Nurses are often in the middle of the minefield and are pushed and pulled by forces, which are sometimes beyond their control. This paper signposts some of the more problematic areas of practice so that nurses may be equipped with at least a broad over-view of the ethical terrain. PMID- 11221147 TI - Changing practice through action research: an interview with Rachel Stevenson. Interview by Pamela J. Wood, Lynne S. Giddings. AB - Nurses and midwives in Aotearoa/New Zealand use a broad range of research methodologies to explore aspects of practice. This is the second article in a series based on interviews with nursing and midwifery researchers, designed to offer the beginning researcher a first-hand account of the experience of using particular methodologies. This article focuses on action research. After describing briefly the key elements of this methodology, the article presents an interview with Rachel Stevenson (RGON, MA) who used action research to explore the experience of nurses and people with asthma in the secondary care setting. PMID- 11221148 TI - Re-introducing Mabel Mahinarangi Kewene, MBE, QSO. Interviewed by Yvonne Shadbolt. PMID- 11221149 TI - Coronary risk factors in Malaysia: precious little is known, ... still. PMID- 11221150 TI - Comparison of Fluvoxamine alone, Fluvoxamine and cognitive psychotherapy and psychotherapy alone in the treatment of panic disorder in Kelantan--implications for management by family doctors. AB - This paper reports the result of a brief therapy attempt at treating panic in a busy outpatient psychiatric clinic. The patients were cases of panic referred from the various outpatient clinics within the hospital complex. The patients were divided into three groups at random using one of three modalities of treatment, i.e. cognitive behaviour therapy (CBT), CBT and Fluvoxamine (FVX), and FVX alone. The therapy was aimed for a maximum of nine sessions after which the patients were to be discharged. There were 14 patients in each group. The results show that all the groups were similar in the severity and scores pre treatment but after the different types of treatment there was a significant difference among them. The FVX alone group, showed significant improvement from the pretreatment levels but did not show as much improvement as the other groups and the mean score was only 9.07 after nine sessions. The best group was the CBT in combination with FVX. This indicates that the best way to treat panic is to combine drug treatment and psychological treatment. It is also shown from the study that the combination group requires less FVX than the FVX alone group. This finding has implications for the treatment of panic at the family physician clinic. PMID- 11221151 TI - Genetic causes of familial hypercholesterolaemia in a Malaysian population. AB - A total of 86 unrelated Malaysian patients with familial hypercholesterolaemia (FH) were studied for mutations in their low-density lipoprotein receptor (LDL-R) gene. Amongst them, 23 had a LDL-R gene mutation, while none having an Apolipoprotein B-3500 (Apo B-3500) mutation. Patients with the LDL-R gene defect appeared to have a higher level of low-density lipoprotein cholesterol (LDL-C), an increased incidence of xanthomas and coronary heart disease (CHD), but no relationships were found between the type of LDL-R gene mutations and their lipid levels or clinical signs of CHD. In contrast to Western data, our findings seemed to indicate a predominance of mutations in the ligand binding domain and an absence of Apo B-3500 gene mutation. The latter finding may offer a genetic basis as to why Asian patients with familial hypercholesterolaemia have lower LDL-C levels and less premature CHD than their Western counterparts. PMID- 11221152 TI - Parental response and understanding towards febrile convulsion. AB - A questionnaire survey was conducted on parents of 58 patients admitted with febrile convulsion (FC) over a 4 month period to the University of Malaya Medical Centre, Kuala Lumpur to determine parental response towards febrile convulsion in their child and their understanding of home management of FC. RESULTS: The majority of parents (93%) were frightened or were in a panic state on witnessing FC in their child. Most (77.6%) of them were able to bring their child to medical attention within 30 minutes, with delays attributed to transport problems. Parental understanding on FC was deficient, particularly with regard to home management of acute seizures. The parents' main source of information was friends and relatives. CONCLUSIONS: Urgent intervention to counsel and allay fears of parents who have just witnessed an acute FC in their child is required. More effort must be made to educate parents about FC, with particular reference to home management of seizures. PMID- 11221153 TI - Pattern of congenital heart disease and access to tertiary cardiac care in Malaysia. AB - This prospective, descriptive study was carried out to determine the pattern and the type of congenital heart disease seen in the Paediatric Departments in 4 government hospitals. The accessibility of surgical or transcatheter interventional treatment was also assessed. Consecutive new patients seen for suspected congenital heart disease from 1/1/95 till 31/12/95 (Group I) were registered. Records of patients seen from 1/1/95 to 31/8/95 (Group Ia) were reviewed 6 months after presentation to determine the nature of treatment received. Group II were cardiac patients who were first seen prior to the year 1995 and had undergone cardiac surgery or transcatheter interventional procedures in 1995. Of the 375 patients registered in the 4 hospitals, 250 were new patients and 125 were patients first seen prior to 1995 and had surgery or transcatheter interventional procedures in 1995. Of the 250 new patients, 83.2% had acyanotic cardiac lesions and 16.8% had cyanotic lesions. Ventricular septal defect was the commonest lesion, constituting 37.2%, followed by patent arterial duct (18.8%) and atrial septal defects (9.6%). At 6 month review, access to close-heart surgery or transcatheter interventional treatment were readily available. However, for patients with ventricular septal defects, 42.1% who required closure were still waiting for surgery 6 months after presentation. Of the 4 patients with Fallot's Tetralogy who required surgery, 2 had modified Blalock-Taussig shunt and 2 were awaiting surgery. In 1995, a total of 204 cardiac procedures were performed, there were 114 (55.9%) open heart procedures, 50 (24.5%) surgical ligation of the arterial duct, 28 (13.7%) modified Blalock-Taussig shunts, 11 (5.4%) transcatheter duct occlusion and 1 (0.5%) balloon valvuloplasty. The mean age of Fallot's Tetralogy repair was 6.4 years. No corrective surgery was performed for patients with complex cardiac lesions from the 4 hospitals in 1995. In conclusion, the pattern of congenital heart disease was similar to that seen world wide. Except for patent arterial duct, access to surgical treatment was inadequate. PMID- 11221154 TI - The role of preoperative magnetic resonance imaging in internal derangement of the knee. AB - We attempted to compare the accuracy of our clinical examination and the usage of magnetic resonance imaging (MRI) in evaluating patients suspected of having internal derangement of the knee who were seen in our Orthopaedic clinic. This was done using the findings of arthroscopy as the 'gold standard'. The accuracy of MRI in detecting cruciate ligament tears was between 80-96% against 82-93% for clinical examination. MRI accuracy for meniscus injuries was 80-84% compared to 48-65% for clinical examination. We thus propose that MRI examination is an effective first-line investigation for patients with suspected internal knee derangement, especially menisci injuries; allowing arthroscopy to be reserved for patients in whom surgery is truly indicated. PMID- 11221156 TI - Preferential utilization of healthcare systems by a Malaysian rural community for the treatment of musculoskeletal injuries. AB - The preferential utilization of healthcare systems by a rural Malaysian community in Perlis for the treatment of musculoskeletal injuries was studied using focus group discussions. The objectives of the study were to explore the pattern of utilization of healthcare systems, the factors influencing the choice of a healthcare provider, rural residents' expectations of their healthcare provider and their views on integrating traditional and modern scientific healthcare systems. Most participants considered traditional and modern scientific healthcare systems as complementing each other. For musculoskeletal injuries, the traditional system was considered the primary choice of healthcare regardless of the participants' socioeconomic and educational levels. Key factors for preferring traditional care were the nature of treatment, the perceived shorter duration for recovery and inclusion of spiritual elements in the therapy. Barriers to seeking hospital treatment were the perceived longer duration for recovery, fear of surgery, use of metallic implants and casts that were culturally unacceptable and objections from elders. For perceived life threatening situations, in children, pregnancy, and where injuries to internal organs were suspected, hospital treatment was preferred as the primary choice. Discussions on integrating traditional and modern scientific systems were inconclusive. PMID- 11221155 TI - Blood pressure, body mass index, heart rate and levels of blood cholesterol and glucose of volunteers during National Heart Weeks, 1995-1997. AB - The paper presents the results of a health screening programme conducted in 10 major centers in Malaysia--Kuala Lumpur, Penang, Ipoh, Johor Bahru, Alor Star, Kuala Terengganu, Malacca, Kota Bahru, Kuching and Kota Kinabalu during the National Heart Weeks, 1995-1997. There were 6,858 participants of both sexes aged between 6 years to 81 years old. The parameters involved in the screening programme were body mass index, blood pressure, heart rate, cholesterol and glucose. The following are the results of the study:- 1. The mean and standard deviation for the body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), total cholesterol (TC) and non fasting (random) blood glucose (GL) of the volunteers studied were 24.3 +/- 4.0 kg/m2, 128.3 +/- 21.1 mmHg, 79.6 +/- 11.9 mmHg, 77.2 +/- 12.1 bpm, 5.33 +/- 1.37 mmol/l and 5.11 +/- 1.97 mmol/l respectively. 2. There was a rising trend for BMI, SBP, DBP, TC and GL with age. The HR was higher in the younger age group of those below 20 years. Males tended to have higher mean values than females except for HR which was similar in both sexes. 3. The Malays, Chinese and Indians seemed to have closely similar mean values for SBP, DBP and HR but the Indians possessed the highest BMI (25.62 +/- 3.90 kg/m2), TC (5.61 +/- 1.48 mmol/l) and GL (5.41 +/ 2.43 mmol/l) among the three major ethnic groups. While the Ibans had highest TC (6.07 + 1.09 mmol/l), their GL level was the lowest (4.76 +/- 1.15 mmol/l). The Kadazans had the lowest TC level (4.94 +/- 1.39 mmol/l) among all the ethnic groups. 4. Among the participants screened, 31.9% were overweight (BMI > or = 25), 7.6% were obese (BMI > or = 30); 26.8% had raised SBP (> or = 140 mmHg) and 19.3% had raised DBP (> or = 90 mmHg); 13.6% of the participants had increased HR (> or = 90 bpm), 22% had raised TC (> or = 6.20 mmol/l) and 2% had raised GL (> or = 11.00 mmol/l). There was a higher prevalence for abnormal values with increasing age until between the ages of 60 or 70 years, when the values began to fall. 5. Age was positively correlated with SBP (r = 0.41***, df = 4351), DBP (r = 0.27***, df = 4351), TC (r = 0.22***, df = 3303) and GL (r = 0.16***, df = 2442) but negatively correlated with HR (r = -0.13***, df = 4351). The BMI was positively correlated with SBP (r = 0.29***, df = 2769), DBP (r = 0.31***, df = 2769), TC (r = 0.16***, df = 2137) and GL (r = 0.11**, df = 1637) but there was no correlation with HR (r = 0.03NS, df = 2771). The SBP and DBP were highly correlated with each other (r = 0.75***, df = 4351) and they also showed highly significant positive correlation (r = 0.08***-0.13***, df = 2441-3301) with TC and GL. TC was positively correlated with GL (r = 0.05* df = 2319) but only at the 5% probability level. PMID- 11221157 TI - Neurological manifestations of children with systemic lupus erythematosus. AB - In a cross-sectional study of 21 children with Systemic Lupus Erythematosus, 15 (71%) were found to have neuropsychiatric manifestations. The most common finding was generalised seizures (42.8%) followed by encephalopathy (19%) and hallucinations (19%). One child (4.76%) had hemichorea. In 3 children neurological manifestations were the first symptom of SLE. Computerised Axial Tomograms (CAT scans) showed cerebral atrophy in 7 of 12 scans available for review. Ten children had abnormal EEGs. Although none of the children had clinical evidence of a peripheral neuropathy, 8 had neurophysiological evidence of a neuropathy. One child died of intracranial haemorrhage. Six children had residual neuropsychiatric sequalae. PMID- 11221158 TI - The yield for colorectal cancer and adenoma by indication at colonoscopy. AB - Colonoscopy is an integral part of the clinician armamentarium in the diagnosis of colorectal cancer and its precursor, the adenoma. Polypoid lesions when identified can be excised at colonoscopy and in turn reduce the risk of colorectal cancer. We prospectively evaluated the yield of colorectal cancer and adenomatous polyps by indication for colonoscopy over a one-year period. A total of 375 colonoscopies were carried out. The more common indications of colonoscopy were rectal bleeding, abdominal pain, surveillance of colorectal cancer and altered bowel habit. The highest yield for cancer was for rectal bleeding with 12.5% while surveillance of patients with a history of polyps yielded the highest percentage of new polyps. We conclude that rectal bleeding as an indication for colonoscopy yielded the highest number of cancers. PMID- 11221159 TI - Transradial coronary angioplasty and stenting--immediate results and 3-month clinical follow-up in the first 50 patients performed at the National Heart Institute. AB - AIM: To explore the safety and feasibility of coronary angioplasty and stenting via the radial artery in a heterogenous group of patients and to report the immediate and 3-month clinical follow-up. BACKGROUND: The use of the transradial approach for coronary angiography was first described by Lucien Campeau in 1989. Based on the favourable initial results, this technique has gained widespread acceptance worldwide. Ferdinand Kiemeneij's work in transradial angioplasty and stenting has taken invasive cardiology into the exciting new era of "minimally invasive coronary intervention". METHODS AND RESULTS: Fifty consecutive patients underwent Transradial Percutaneous Transluminal Coronary Angioplasty (PTCA) with or without stenting from mid March 98-December 98. The right radial approach was utilised in 41 patients (80%) while the left in 9 patients. Ninety percent of the procedures was done on an adhoc basis. Diabetes mellitus was present in 38% of patients. Eighty percent of patients had unstable angina pectoris and 60% had a prior history of acute myocardial infarction. The commonest vessel involved was the LAD (51%) and type B lesions predominated (54%). PTCA was successful in 96%. One patient had a total LAD occlusion, which could not be wired, and another developed severe spasm during catheter manipulation. The latter had successful PTCA via the right femoral route Stents were utilised in 57% of patients. The commonest indication for stenting was suboptimal PTCA results (89%) and dissection (14%). There was no stent embolisation and all stents were successfully deployed (100%). One patient developed acute stent thrombosis necessitating repeat PTCA and another patient sustained an acute anteroseptal myocardial infarction 5 days post procedure as a result of subacute stent thrombosis and died. Two patients had successful primary PTCA. There was no bleeding or vascular complications. 60% of patients were treated on an outpatient basis. At 3-months follow up, 1 patient required CABG's for disease progression. Three patients had absent radial pulses without adverse consequence. No patient required repeat PTCA at follow up. CONCLUSION: In summary, adhoc PTCA and stenting is safe and feasible in our patient population. A study on the cost effectiveness of the procedure compared to conventional femoral PTCA is warranted. PMID- 11221161 TI - The health care professional's attitudes towards brain death and cadaveric organ transplantation: the influence of cadaveric donor and transplantation programs--a Malaysian survey. AB - One of the main reasons for poor response in organ donation is the lack of positive attitudes and knowledge present in health care professionals. Definite legislation, policies and programmes dealing with brain death and cadaveric organ transplantation have shown some favourable results in terms of increasing donor rates. These programmes are mainly Western based; therefore adopting such programmes to be used locally may not be adequate or proper. To address this issue, we decided to carry out a questionnaire in two tertiary hospitals in Malaysia, one with a well establish brain death and cadaveric organ transplantation programme and one with none. PMID- 11221160 TI - Intrahepatic stones: the UKM experience. AB - Intrahepatic stones remain a major source of morbidity and mortality. With improving techniques in hepatobiliary surgery, the management and the outcome of intrahepatic calculi is reviewed. Forty-nine cases referred from all over Malaysia between January 1993 to June 1996 were analyzed retrospectively. There were thirty-two females and seventeen males. The median age was 46 years. Biliary diseases encountered in association with intrahepatic calculi included benign strictures (n = 14), ascariasis (n = 3), cholangiocarcinoma (n = 1), Caroli's disease (n = 1), and thalassaemia, (n = 1), fifty-six percent of stones were located in both the intrahepatic ducts while 34% were found in the left intrahepatic duct. Thirty-one patients underwent common bile duct exploration either alone or in combination with liver resection or bilioenteric anastomosis. Despite the various combinations of surgical and non-surgical intervention 28 (57.1%) patients had residual stones. Despite the availability of newer techniques in hepatobiliary surgery, residual stones were common, resulting in higher treatment costs. PMID- 11221162 TI - A study of clinical questions in primary care. AB - This is a prospective study of clinical questions generated in primary care consultations and a comparison of two approaches to answering those clinical questions. Twenty-one doctors in a university-based primary care clinic submitted 78 clinical questions arising from patient consultations during 24 clinic days (0.01 question per patient encounter). These doctors subsequently found answers to 40% of their questions but were satisfied with only 67% of these answers. The investigators were able to provide answers for 95% of the questions asked and the doctors rated these answers as satisfactory in 86% of instances. Answers obtained by investigators had significantly higher satisfaction score than those obtained by doctors' search (p = 0.002). The two main findings of this study are (1) almost all questions arising in clinic setting could be answered by intensive search; (2) answers found by intensive searches were judged to be more satisfactory than those found routinely by doctors. Provision of an information retrieval service in addition to training in the searching and appraisal of medical literature are possible solutions to the information needs of busy clinicians. PMID- 11221163 TI - Combined oral and parenteral iron chelation in beta thalassaemia major. AB - Thalassaemics in Malaysia are poorly chelated because desferrioxamine is too expensive and cumbersome for long term compliance. The efficacy and tolerability of the oral chelator deferiprone, and the effects of using a combination therapy in our patients were studied. Ten patients completed the study and the mean serum ferritin reduced from 7066.11 ug/L (2577-12,896 ug/L) to 3242.24 ug/L (955-6120 ug/L). The liver iron concentration did not show a significant drop (19.6 vs 18.2 mg/g dry weight) although 3 patients showed reductions ranging from 30-40%. Concomitant use of desferrioxamine increased the urinary excretion from a mean of 13.66 mg/day to 27.38 mg/day. Main side effects seen were nausea and rashes. PMID- 11221164 TI - Upper gastrointestinal bleeding in Kuala Lumpur Hospital, Malaysia. AB - Despite advancements in endoscopy and pharmacology in the treatment of peptic ulcer disease the overall mortality has remained constant at 10% for the past four decades. The aim of this study was to determine the age, gender, racial distribution, incidence and causes of endoscopically diagnosed cases of upper gastrointestinal (UGI) bleeding to summarise treatments undertaken and to report their outcome. A prospective study of UGI bleeding in 128 patients was performed in two surgical wards of Kuala Lumpur Hospital, involving both elective and emergency admissions. The study group comprised of 113 (88.2%) males and 15 (11.7%) females. The mean age was 51.9 years (range 14 to 85 years) and 37.5% (48 of 128 patients) were older than 60 years. The Indian race was over-represented in all disease categories. Smoking (50.1%), alcohol consumption (37.5%), non steroidal anti-inflammatory drugs (NSAIDs) (17.2%), traditional remedies (5.5%), anti-coagulants (2.3%) and steroids (0.8%) were among the risk factors reported. Common presenting symptoms and signs included malaena (68.8%), haematemesis (59.4%) and fresh per rectal bleeding (33.6%). The commonest causes of UGI bleeding were duodenal ulcer (32%), gastric ulcer (29.7%), erosions (duodenal and gastric) (21.9%), oesophageal varices (10.9%) and malignancy (3.9%). UGI bleeding was treated non-surgically in 90.6% of cases. Blood transfusions were required in 62.6% (67/107) of peptic ulcer disease patients. Surgical intervention for bleeding peptic ulcer occurred in around 10% of cases and involved under-running of the bleeding vessel in most high risk duodenal and gastric ulcer patients. The overall mortality from bleeding peptic ulcer disease was 4.7%. Six patients died from torrential UGI haemorrhage soon after presentation, without the establishment of a cause. Active resuscitative protocols, early endoscopy, more aggressive interventional therapy, early surgery by more senior surgeons, increasing intensive care unit beds and more active participation of multidisciplinary teams in co-ordinating management are among remedial measures advocated. Broader educational preventive strategies should target the causes of UGI bleeding. PMID- 11221165 TI - Blood pressure values in healthy Malaysian children aged 6-12 years. AB - Blood pressure examination was done manually in 1756 healthy school children aged 6-12 years. Korotkoff 1 represented the systolic blood pressure (SBP) and Korotkoff 5 was taken as the diastolic blood pressure (DBP). Blood pressure percentile charts were then drawn up based on age group and sex regardless of ethnicity. There was a significant correlation between both SBP and DBP to increasing height, weight and body mass index. PMID- 11221166 TI - Successful pregnancy in a patient with familial sea-blue histiocyte syndrome. AB - A 27-year-old Indian woman at 23 weeks' gestation presented with decompensated liver cirrhosis, coagulopathy, restrictive lung disease with cor pulmonale and preeclampsia. She was diagnosed to have sea-blue histiocyte syndrome (SBHS) at the age of 13 years and was treated conservatively. There was worsening liver, respiratory and bone marrow function as the pregnancy progressed. She underwent a successful pregnancy despite her poor medical condition and advanced disease state. We described the first case of familial SBHS in a pregnant patient from Asia. PMID- 11221168 TI - Resection of large primary chest wall chondrosarcoma with reconstruction: 2 case reports. AB - We report two cases of large chest wall primary chondrosarcoma, one of the sternum and the other of the lateral chest wall. Both were treated by radical resection and reconstruction using marlex mesh and methyl methacrylate "sandwich" prosthesis and pedicled latissiumus dorsi flap. PMID- 11221167 TI - Transient hyperthyroidism following L-asparaginase therapy for acute lymphoblastic leukemia. AB - The effect of L-asparaginase on the thyroid gland has not been well documented. We report the first two cases of hyperthyroidism associated with thyroid nodule following L-asparaginase therapy for acute lymphoblastic leukemia (ALL). The thyroid function abnormalities were not severe, short-lived and did not require specific therapy. PMID- 11221169 TI - Pneumonia presenting as acute abdomen in children: a report of three cases. AB - From 10th September 1998 till 5th June 1999, the Paediatric and Cardiothoracic Surgery Units of Sultanah Aminah Hospital Johor Bahru managed three children with lung collapse secondary to pneumonia. The dominant initial clinical presentation in all three cases was acute abdominal pain. Basal pneumonia was diagnosed in two cases post-operatively after surgical contributory causes were excluded intra operatively. Thoracotomy, evacuation of infected debris and decortication of the collapsed lung was done in all three cases. In children presenting with acute abdominal pain, basal pneumonia should be considered as a possible contributory cause. PMID- 11221171 TI - Life threatening pancreatitis following varicella vaccination: cause, association or co-incidence? PMID- 11221170 TI - Neuropsychiatric profile of a case of post traumatic stress disorder following an electric shock. AB - Exposure to extraordinary stressors or life-threatening events has been shown to result in negative cognitive, behavioural and emotional outcomes including the cluster of symptoms constituting Post Traumatic Stress Disorder (PTSD). This disorder has most often been studied in military veterans and victims of abuse who also show high rates of comorbid conditions. We report a case of PTSD following an electrical injury in a patient with no past psychiatric history. Implications for a full range of examinations including comprehensive neuropsychiatric testing are discussed. Results suggest that such approach addresses the complexity of a differential diagnosis between organic and psychiatric dysfunctions. PMID- 11221173 TI - Faculty matters. Rose Ann Dimaria. PMID- 11221172 TI - Primary pulmonary hypertension. World Health Organization. AB - Primary pulmonary hypertension (PPH) is a rare disease. The annual incidence in the West is 1-2 cases per million population per year. A recent WHO symposium in 1998 has produced a consensus on classification, methods of screening, risk assessment and treatment. PPH is a diagnosis of exclusion after all other secondary causes of pulmonary hypertension are ruled out. Current treatment strategy involves acute vasodilator drug trial where positive responders are treated with high dose calcium channel blockers and anticoagulation. Those who do not show positive response may be commenced on intravenous prostacyclin. Surgical treatment is one option for patients with severe PPH or for symptomatic relief. Prognosis in general is very poor. PMID- 11221174 TI - Why women and men choose nursing. AB - The purpose of this study was to compare and contrast why women and men choose nursing. Male and female nursing students enrolled in a baccalaureate nursing program at every class level were interviewed over a two-year period. The interviews enabled the subjects to give voice to their motivations, needs, and expectations. Data were obtained and analyzed using grounded theory methodology. The analyses, performed both by the author and by a second intercoder, included constant comparison with substantive and categorical coding for the purpose of theory generation. While male and female students demonstrated comparable commitment to care for their patients, differences emerged within the construct of power. In addition, there was a strong contrast between male and female students regarding practical motivations for choosing nursing (e.g., salary and working conditions). PMID- 11221175 TI - Building roads with a clear vision and a wide perspective. PMID- 11221176 TI - Partnerships in primary health care. A process for re-visioning nursing education. AB - This article describes the process of curriculum change in a baccalaureate nursing program and the design of a competency-oriented learning system in primary health care, community-focused nursing education. PMID- 11221177 TI - Community partnership. A school of nursing creates nursing centers for older adults. AB - A southeastern university school of nursing responded to a request by a local housing authority to provide nursing care and health promotion to the residents of three high-rise complexes for independent living for seniors. This service learning partnership offers differing educational benefits to graduate and undergraduate nursing students while helping residents remain as well as possible. PMID- 11221178 TI - A proposed framework for differentiating the 21 Pew competencies by level of nursing education. AB - Now nearly a decade old, the original Pew Health Professions Commission Competencies have stood up well to the test of time. The competencies were designed to provide all health professionals, from physicians to physical therapists, with a general guide to the values, skills, and knowledge they would need to be successful in the health care system that was beginning to emerge in the late 1980s. They have been used across the range of health professions and in many practice settings to create a framework for curricular change, work redesign, and assessment of professional competence. The interpretation of the competencies offered here should prove to be a useful tool to nurses and health system leaders as they carry on the hard work of adapting the current model of nursing practice to the demands and realties of the contemporary and continually evolving health care environment. This work is important for two reasons. First, many of the skills and attributes of the professional nurse are not adequately used or valued by the health care system because the profession is both fragmented and poorly differentiated and articulated. Without markers that define and promote collaborative practice within nursing, the full potential of nurses at all levels of preparation will continue to be inadequately and inappropriately deployed. This model exacerbates the current nursing shortage because it fails to use nurses in appropriate, well-delineated, and challenging roles. Without this kind of differentiation, one that can be owned and supported by all nurses, there will continue to be suboptimal use of the nursing workforce in the United States. The framework of differentiated Pew competencies and the companion teaching learning strategies proposed here offer one approach to rationalizing both nursing education and practice, with the potential for improving the quality of care, and reducing fragmentation, cost, and public confusion. PMID- 11221179 TI - Listen to your students. PMID- 11221180 TI - Why accreditation? Quality care is everyone's responsibility. PMID- 11221181 TI - What is the relationship of collegiality to accreditation. PMID- 11221182 TI - Weekly rounds. PMID- 11221183 TI - The advancement of baccalaureate and graduate nursing education: 1952-1972. PMID- 11221184 TI - Drug treatment of neuropathic pain. AB - Neuropathic pain results from damage to or dysfunction in the nervous system. The term usually refers to pain caused by a primary abnormality in the peripheral nervous system, while pain caused by damage to the central nervous system tends to be called central pain. Once established, neuropathic pain frequently runs a chronic course and can be severe and difficult to treat. Most doctors (but especially GPs, neurologists, neurosurgeons, oncologists and pain clinic specialists) will encounter patients with neuropathic pain. Management, ideally in a multidisciplinary pain-relief clinic, often involves the combined use of a range of pharmacological and non-drug approaches, the latter including transcutaneous electrical nerve stimulation, psychological treatments, and specialist procedures to stimulate, block or destroy discrete areas of the nervous system. Here, we review just the drug treatments for neuropathic pain. PMID- 11221185 TI - Why bother about cytochrome P450 enzymes? AB - The cytochrome P450 system is a group of enzymes, found mainly in the liver and gut mucosa, that controls the concentrations of many endogenous substances and drugs. The activity of the individual enzymes can vary over time and from person to person in response to diet, medicines or exposure to environmental pollutants. Here, we review the cytochrome P450 system and consider its relevance to prescribing. PMID- 11221186 TI - Treatment notes--an update. AB - In January 2000, we launched Treatment Notes--our series of leaflets for patients. By December, we had published 10 issues and were pleased to be able to supply a free sample copy of each one with Drug and Therapeutics Bulletin (DTB). However, the cost of printing complimentary copies (over 125,000 of each issue) has become prohibitive and, for the time being at least, Treatment Notes will only be available by order. Here, we review the origin and development of the series and explain the changes. PMID- 11221187 TI - Tackling polycystic ovary syndrome. AB - Up to one-third of women in the UK have polycystic ovaries (i.e. 10 or more follicles per ovary detected on ultrasound). An estimated one-third of these women have polycystic ovary syndrome, usually defined in the UK as polycystic ovaries together with one or more characteristic features (hirsutism, male pattern baldness, acne, oligomenorrhoea or amenorrhoea, obesity, or raised serum concentrations of testosterone and/or luteinising hormone [LH]). The metabolic abnormalities often associated with polycystic ovary syndrome (insulin resistance and abnormal serum lipid concentrations) also put some women with the syndrome at increased risk of developing diabetes mellitus. Here, we review the management of women with polycystic ovary syndrome. PMID- 11221188 TI - What to do about medically unexplained symptoms. AB - Around one in five new consultations in primary care are by patients with physical symptoms for which no specific organic cause is found (medically unexplained symptoms). While many of these symptoms are transient, over one-third persist and can cause distress and disability. Here, we discuss strategies for the management of adults with medically unexplained symptoms. PMID- 11221189 TI - [Prevention and rehabilitation instead of hospitalization and treatment]. PMID- 11221190 TI - [Nursing research has patients and nurses in view]. PMID- 11221191 TI - [Nurses as movers in a successful interdisciplinary cooperation]. PMID- 11221192 TI - [Well founded knowledge in gerontology and social rules are the basis of geriatric nursing]. PMID- 11221193 TI - [Managing chronic pain. Relieving pain by relaxation]. PMID- 11221194 TI - [The patient is rarely informed about his examination and care]. PMID- 11221195 TI - [Latex allergy is occurring ever more often]. PMID- 11221196 TI - [Living in darkness--treating the blind]. PMID- 11221197 TI - [Fire safety in hospitals: 26 questions to the fire fighters]. PMID- 11221198 TI - [Diagnosis Related Groups inspire multiprofessional patient care team]. PMID- 11221199 TI - [Managing ever growing demand for supervisory leading personnel]. PMID- 11221200 TI - [Women, leaving school, considering the nursing profession]. PMID- 11221201 TI - [Criticism is often hidden behind friendliness]. PMID- 11221202 TI - [Voice of nurses from all over the world]. PMID- 11221203 TI - [Where nursing services still are missing]. PMID- 11221204 TI - [Reflections on phenomenological research in nursing]. AB - This essay is concerned with the question which philosophical traditions underpin the phenomenological perspective in nursing research. The word phenomenology is often used synonymously on the level of the theory of science as well as on the level of research methods. Besides the similarity in the designation of phenomenology as a philosophical tradition and as a research method, there are to be found a number of terms in the nursing literature, such as hermeneutic, interpretive or interpretative phenomenology. Therefore it is hard to differentiate between the various accounts and to use them for a concrete inquiry in nursing. The differences and the resulting consequences for phenomenological research methods shall be described whereby the ideas of Edmund Husserl and Martin Heidegger are taken into account. PMID- 11221205 TI - [The care of adults in persistent vegetative state--a new challenge to nursing science?]. AB - German scientists assume that new problems in nursing practice can be credited to an increasing number of accident-based long-term handicaps (Robert Bosch Stiftung 1996). This hypothesis is supported by epidemiological data as elaborated in the following article. Furthermore the critical examination of the terms "apallic syndrome" and "persistent vegetative state" leads up to the question which medical assumptions in relation to the phenomenon of the apallic syndrome are transferred to nursing. According to Feuser (1995) and for noted reason the medical perspective on the apallic syndrome appears to be similar to what can be observed in the practice of psychiatric care. This inheritance of medicine offers a new challenge to the nursing discipline which consequently will have to strengthen the own science. PMID- 11221206 TI - [Nursing relevance of the bases of the concept of Salutogenesis]. AB - The objectives of nursing are closely tied with the meaning of health. This means for the development of nursing science to come to an understanding of new concepts of health which have been developed in health sciences recently. Therefore the model of Salutogenese is presented. The author discusses the key concepts like the health-disease-continuum, the sense of coherence and the generalized resistance resources in regard to relevance for nursing in theory and practise. PMID- 11221207 TI - [Advanced and continuing education is an important indicator of professional satisfaction in nursing]. AB - The subject of this quantitative study is the job-satisfaction of nursing staff at the Freiburg Tumorbiology Clinic. The aim was to identify factors which influenced job-satisfaction. Originally 127 questionnaires were distributed and the final evaluation was based on 89 completed returns. With the information, using factor analysis, we identified nine factors. One of the factors, continuing education was interpreted and evaluated in detail. The results showed that in general women including managers and supervisors have a more positive attitude toward further training than men. The data could not confirm if a positive attitude toward training positively influenced job-satisfaction or that a prior satisfaction with the job leads to a positive attitude towards training. What is clear is that continuing education enables employees to be more competent and handle more responsibility. From the point of view of both the employees and employers it is necessary to have constantly updated knowledge to ensure highest quality of nursing care. PMID- 11221208 TI - [Long-term job satisfaction in direct nursing care]. AB - In this study the qualitative method of grounded theory was employed to investigate what enables nurses to work long-term in direct nursing care and being satisfied. This question is of actual importance in the present situation of rising costs in the health care system and increasing work pressure for the nursing staff. Five nurses with at least ten years of work experience participated in seven interviews. Data analysis revealed coping with difficulties as the core concept. All respondents had to deal with difficult situations in their daily working routine, which occasionally have been experienced as overwhelming. Important conditions for coping with difficulties are the personal development, the cooperation with others and the taking care of oneself. If this can be done successfully, it is possible to take over central responsibilities in nursing care, to act in a competent and purposeful way, and to care for others, which is a condition for long-term job satisfaction. The focuses described in the literature--cooperation, engagement and coping with stress--were found as central contents in this investigation. The findings for the most part are congruent with the results of other studies. The implications for practice focus on working conditions and possibilities of support, which help nurses to deal with the difficulties encountered in their daily work. PMID- 11221209 TI - [Reliability and validity of the Braden Scale for predicting pressure sore risk]. AB - For more accurate and objective pressure sore risk assessment various risk assessment tools were developed mainly in the USA and Great Britain. The Braden Scale for Predicting Pressure Sore Risk is one such example. By means of a literature analysis of German and English texts referring to the Braden Scale the scientific control criteria reliability and validity will be traced and consequences for application of the scale in Germany will be demonstrated. Analysis of 4 reliability studies shows an exclusive focus on interrater reliability. Further, even though examination of 19 validity studies occurs in many different settings, such examination is limited to the criteria sensitivity and specificity (accuracy). The range of sensitivity and specificity level is 35 100%. The recommended cut off points rank in the field of 10 to 19 points. The studies prove to be not comparable with each other. Furthermore, distortions in these studies can be found which affect accuracy of the scale. The results of the here presented analysis show an insufficient proof for reliability and validity in the American studies. In Germany, the Braden scale has not yet been tested under scientific criteria. Such testing is needed before using the scale in different German settings. During the course of such testing, construction and study procedures of the American studies can be used as a basis as can the problems be identified in the analysis presented below. PMID- 11221210 TI - [The institutionalized elderly. How do we perceive old age?]. AB - It is a commonly-held belief to associate old age with physical deterioration, loss of mental capacity and a downhill slide toward death. Although one cannot deny some aspects of truth in this belief, what is certain is that the perception which each person holds about old age, as well as each person's real life situation, will make each individual live this stage of life in very diverse manners. We may affirm that quality of life is a criteria set and evaluated by each human being, and in order to evaluate it, one's personal opinion and satisfaction are indispensable. What does quality of life mean for an elderly person who is institutionalized? What do the business administrators, managers and caretaking personnel understand quality of life to be for an elderly person who is institutionalized? Are there differences perceiving quality of life between personnel and elderly? The authors carry out this study in order to answer these kinds of questions by means of a descriptive and transversal method; one objective is to evaluate the perception of quality of life for institutionalized elderly held by each of the aforementioned groups. The study group for this research project was composed of elderly people living as permanent residents in an institution and the business administrators, managers and caretaking personnel in three geriatric centers in Navarra; there was a total of 90 people in the sample group. PMID- 11221212 TI - [Nursing education in the United States]. PMID- 11221211 TI - [Poisoning by organophosphate insecticides. Epidemiology and prevention]. AB - In an agrarian environment, exposure to anticholinesterasic insecticides is a potential health problem. Acute or chronic intoxication may cause serious health problems due to its frequency or its severity. Extremadura is, as are other Spanish autonomous regions, mainly a rural environment which means that this problems carries special relevance there. In this article, the authors evaluate the number of cases of intoxication, the validity of the measures taken, and they describe the pedagogical programs which exist dealing with this problem. They review the physiopathological causes of this intoxication, its symptoms and its treatment. The authors reveal the results obtained from a questionnaire given to a group of Extremaduran farmers. Furthermore, the authors provide information to health professionals responsible for the treatment and prevention of this intoxication; the authors consider health education, especially in an agrarian environment, to be one of the most important action plans in order to prevent this intoxication and to reduce its mortality and chronic manifestations due to exposure to these agents. PMID- 11221213 TI - [Neutralization of odors in colostomized patients. (multicenter study)]. AB - The purpose of this study is to run a comparative, multi-centric study as a way to research and test two odor neutralizing agents having distinct forms, capsules or liquids. The objective is to identify an odor neutralizing agent which brings a solution to an as yet unsatisfactorily resolved problem, by this means providing greater security and discretion to a patient having undergone a colostomy and increasing that patient's quality of life. This study concludes that the capsule neutralizing agent appears to be the most desired treatment form both in the opinion of those having undergone a colostomy as among the researchers due to its efficiency and ease of use. PMID- 11221214 TI - [Professional unemployment in Andalucia. Expectations and difficulties in the nursing profession]. AB - The primary objective of this article is to know the professional, academic and formative expectations in Nursing and those problems which hinder the performance of this profession among the Andalucian public health centers. The authors carried out an extensive descriptive study during the years 1994-1996 based on a sampling of 1020 nursing professionals pertaining to the Andalucian Health Service. These samples were obtained by means of a random stratification by provinces and care level, with an affixation proportional to the size of the stratum, having a 95% confidence rate and a 3.5% error rate. The data were acquired by means of a self-administered questionnaire sent in by mail. Among the most significant results, the authors highlight that fact that the professional, academic and performance expectations among Andalucian Nursing professionals center on research and investigation (71.5%), postgraduate courses (75%), possible Licentiate in Nursing (82.4%) and some nursing specialty (78.7%). Among the difficulties identified for professional performance, the items which stands out were those derived from the absence of a legal definition for Nursing functions (90.8%). PMID- 11221215 TI - [Cardiotocographic recording during labor: problems and alternatives]. AB - Over the past few years there has been a notable decrease in fetal morbid mortality due to intrauterine asphyxia. Currently there is a controversy about the role which electronic monitoring of uterine contractions and of fetal cardiac frequency during birth has played in the aforementioned decrease. The frequent nonspecificness and/or the subjectivity in interpreting these recordings, coupled with the risk of reducing the direct contact with the mother, are a few of the limitations which can reduce the efficiency of electronic monitoring. Various complementary fetal control methods, some of which in current clinical usage such as fetal scalp pH, fetal EKG, fetal pulsimeter readings, doppler flux metering, or vibra-acoustic stimulation and others which are undergoing testing such as infrared spectroscope can increase the predictive efficiency of electronic monitoring. Some of the ideas included in this article were presented in the VII Course for "New Perspectives in Obstetrics and Gynecology" held in Salamanca. PMID- 11221216 TI - [Nursing concept for AIDS patients]. PMID- 11221217 TI - [Improving the nursing process is in the interest of most nurses]. PMID- 11221218 TI - [Palliative care: improving quality of life instead of prolonging suffering]. PMID- 11221219 TI - [Nursing of patients with chronic pain. I. To understand, evaluate and fight pain]. PMID- 11221220 TI - [Pain in hospitalized tumor patients: not to be taken lightly]. PMID- 11221221 TI - [Financing hospital costs: nursing services must be taken into account]. PMID- 11221222 TI - [What does the introduction of the DRG system mean to hospitals]. PMID- 11221223 TI - [Psychological aspects of fighting stress: activity and relaxation must be well balanced]. PMID- 11221224 TI - [Burnout in the nursing profession: there is help in burnout]. PMID- 11221225 TI - [Nursing of AIDS patients: reflexions on home care of stress]. PMID- 11221226 TI - [Nursing duties in suicide prevention: the patient has right to freedom]. PMID- 11221227 TI - [Death with dignity in the old age home: consideration for the needs of demented patients]. PMID- 11221229 TI - [Aging and physical activity]. PMID- 11221228 TI - [Nutrition and physical capacity in the aged]. PMID- 11221230 TI - [Physical activity and aging in the Auvergne region]. PMID- 11221231 TI - [Equilibrium in the aged, the Troyes experience]. PMID- 11221232 TI - [Light exercise]. PMID- 11221233 TI - [Dietetics. Milk, yogurt and cheese]. PMID- 11221234 TI - [What is the priority for the aged living in an institution?]. PMID- 11221235 TI - [Physical activity at advanced age]. PMID- 11221236 TI - [Water--source of health and wellbeing of the aged]. PMID- 11221237 TI - [New face of the nursing profession in the world, psycho-medical assistance]. PMID- 11221239 TI - [Impact of physical activity on mental and physical health in the aged]. PMID- 11221238 TI - [Aging and physical capacity]. PMID- 11221240 TI - [Nursing care. Keeping and treating elderly incontinent patients at home]. PMID- 11221241 TI - [Low-friction intermittent urinary catheterization]. PMID- 11221242 TI - [United kingdom, distinction between the actual role of nurses and their professional recognition]. PMID- 11221243 TI - [Nursing strategy: 10 commandments for better care of leg ulcer]. PMID- 11221244 TI - [Home care, the nursing network]. PMID- 11221245 TI - [Reflexions on the quality of life in palliative care]. PMID- 11221246 TI - [Following the patient and his nurses]. PMID- 11221247 TI - [End of life at the hospital, psychological questions]. PMID- 11221248 TI - [Mutual protection, a curb in communication]. PMID- 11221249 TI - [Nursing strategy: touching and the end of life]. PMID- 11221250 TI - [Nursing care and spiritual needs of the patient at the end of life]. PMID- 11221251 TI - [Nursing care: palliative care in specialized geriatric nursing]. PMID- 11221252 TI - [The globule diameter and various electron and conformational properties of the flavoprotein fragment of mitochondrial NADH dehydrogenase studied by fluorescence spectroscopy]. AB - The globule dimensions and some electron and conformational properties of the flavoprotein (peripheral) fragment of the mitochondrial NADH dehydrogenase were determined by the time-resolved, phase-modulating, and polarization fluorescence spectroscopies, as well as correlated confocal microscopy. The rotational and the diffusion (translocation) diameters of the protein fragment were shown to be no less than 44 A and approximately 72 A, respectively. The diameter of protomitochondrial particles from the bovine heart, which were used for the isolation of the fraction of peripheral fragments, was no less than 2300 A. The fluorescence from tryptophan and flavin fluorophores in the fragment is strongly quenched by iron of the iron-sulfur clusters, which suggests that a strong electron-vibrational interaction of iron with Trp residues and flavin takes place. An overlapping of the electron clouds of iron-sulfur clusters, Trp residues, and flavin is likely to facilitate the electron transfer through the protein. The heat inactivation of the enzyme was accompanied by neither its substantial conformational changes, nor a considerable release of iron ions from the clusters located near the Trp residues. PMID- 11221253 TI - [Cleavage of RNA in hybrid duplexes by ribonuclease H from E. coli. I. Substrate properties of complexes formed by RNA and tandem of short oligodeoxyribonucleotides]. AB - We studied the E. coli RNase H cleavage of a 5'-labeled RNA fragment within two hybrid duplexes with identical sequences, one of which is formed by RNA and a 20 mer oligodeoxyribonucleotide (RNA/p20), whereas the second, by RNA and a tandem of short oligodeoxyribonucleotides (octanucleotide: (RNA/tandem). It was shown that RNA in the RNA/p20 complex is hydrolyzed from the 3'-end to yield consecutively the 17-, 14-, 11-, 8-, and 5-mer 5'-labeled fragments. On hydrolysis of RNA in complex RNA/tandem, the same products were registered, but their accumulation rates in this case differed. Thus, the initial rates of accumulation of the 17- and 8-mer were close. Moreover, the accumulation of the final 5-mer differed considerably: in the RNA/tandem complex it appeared within first minutes of the reaction, but only after a considerable lag period in complex RNA/p20. These data testify that the tandem is involved not only in the consecutive accumulation of the shortened products (which is characteristic of complexes including extended oligonucleotides) but also in the parallel accumulation. This results from hydrolysis of each duplex segment formed by RNA and the short oligonucleotide of the tandem. Although the order of recognition and cleavage of RNA target by ribonuclease H depends on the type of the hybrid duplex, the destruction of RNA target within complex RNA/tandem and in complex with the full-size oligonucleotide occurs with a close effectiveness. PMID- 11221255 TI - [Structure and physiological activity of lemnan, Lemna minor L. pectin]. AB - A pectic polysaccharide, lemnan, was isolated from freshly collected duckweed Lemna minor L. Its sugar chain was shown to be mainly composed of the residues of D-galacturonic acid (64%), galactose, arabinose, xylose, and D-apiose, a branched chain sugar. The high content of D-apiose (25%) indicated that lemnan is an apiogalacturonan type pectin similar to zosteran, a pectic polysaccharide from a sea phanerogam of the Zosteraceae family. The results of partial acidic hydrolysis, pectinase digestion, and NMR studies of lemnan demonstrated that its macromolecule contains regions of the linear alpha-1,4-D-galacturonan and branched apiogalacturonan. The side chains of apiogalacturonan were found to be formed of single and 1,5-linked residues of D-apiofuranose attached to 2- and 3 positions of the D-galacturonic acid residues of the apiogalacturonan backbone. Lemnan was shown to exhibit an immunomodulatory effect by activating the system of phagocytosis. PMID- 11221254 TI - [Polymethylene derivatives of nucleic bases with omega-functional groups. Pyrimidine derivatives]. AB - N1-Acyclic derivatives of pyrimidine bases (uracil, thymine, and cytosine) with hydrophobic polymethylene chains containing various functional groups in an omega position of the alkyl substituent were synthesized. Their physicochemical properties and inhibitory effect on the HIV reverse transcriptase and human DNA topoisomerase I were studied. PMID- 11221256 TI - [Molecular biology in the year 2000: prediction, realities, and more predictions]. PMID- 11221257 TI - [Molecular biology in the year 2000. 1970]. PMID- 11221258 TI - [Francis Crick: predictions for the year 2000 (Molecular biology in the year 2000) were almost absolutely correct]. PMID- 11221259 TI - [Molecular biology from the year 1970 to 2000 and beyond]. PMID- 11221260 TI - [F. Crick's predictions are not the only ones worth remembering]. PMID- 11221261 TI - [Physico-chemical biology in the first quarter of the XXI century]. PMID- 11221262 TI - [Signal cellular systems and genome]. PMID- 11221263 TI - [Francis Crick about gene activity regulation research]. PMID- 11221264 TI - [Molecular immunology--from immunoglobulin genes to artificial antibodies, from antibodies to biomedicine]. PMID- 11221265 TI - [The unlimited complexity of biological systems and the astonishing diversity of living organisms will remain the driving force behind physico-chemical biology in the first third of the XXI century]. PMID- 11221266 TI - [Life in dynamics]. PMID- 11221267 TI - [Molecular biology at the turn of the third millenium]. PMID- 11221268 TI - [Frontiers of the year 2000 in science and technology]. PMID- 11221269 TI - [Some comments regarding F. Crick's paper]. PMID- 11221270 TI - [Effect of S-adenosyl-L-methionine and its analogs on site-specific binding DNA (adenine-N6)-methyltransferase from T4 phage to the oligonucleotide substrate]. AB - Using fluorescence of 2-aminopurine-substituted oligonucleotide duplexes, "flipping" of the target base in the process of interaction of T4 DNA-(adenine N6)-methyltransferase (EC 2.1.1.72) with the substrate double-stranded DNA was revealed. It was shown that S-adenosyl-L-methionine, the methyl group donor, induces the reorientation of the enzyme relative to the asymmetrically modified recognition site. PMID- 11221271 TI - Statins early in acute coronary syndromes. PMID- 11221272 TI - Transoesophageal echocardiography: a role for district hospitals? PMID- 11221273 TI - Transoesophageal echocardiography: its role in the management of patients in a district general hospital. AB - The aim of this study was to assess the value of a transoesophageal echocardiography (TOE) service in a district general hospital (DGH). A series of 151 consecutive cases was analysed retrospectively to determine the relative additional benefit of TOE over transthoracic echocardiography (TTE) in establishing diagnoses and making therapeutic decisions. Of the 151 cases, 140 were suitable for the two procedures to be compared. In 56%, TOE provided useful information for patient management. This consisted of the detection of new major findings (33%) and the exclusion of significant abnormalities (23%), suspected either clinically or by TTE. TOE made a minor clinical contribution in 8% of cases, while in 30% there was concordance between the two studies. Finally, in 6% both examinations were inconclusive. We conclude that TOE has a significant complementary role to TTE in terms of clinical diagnosis and patient management in the DGH setting. PMID- 11221274 TI - A cross-sectional survey of the clinical and psychological features of low back pain and consequent work handicap: use of the Quebec Task Force classification. AB - A hospital-based cross-sectional study examined 657 consecutive referrals with low back pain over two years to a district rheumatology service serving a population of about 250,000 people. Five hundred and thirty-eight had mechanical/degenerative low back pain. The mean age was 48.6 (range 18-80 SD 15.3) years; 64% were women. Patients with radiating pain or neurological deficit (Quebec Task Force classification) were significantly more disabled (Roland disability score p < 0.001) and depressed (Modified Zung score p < 0.05) than those without radiating pain. Women were more impaired (p = 0.02) than men but had similar disabilities (mean Roland score 11.7, range 0-24 SD 6.5). Fifty-three per cent of patients were receiving benefits and were significantly more likely to have musculoskeletal comorbidities than those in work (p < 0.025). It is concluded that the Quebec Task Force classification of low back pain impairment is a helpful descriptor and related to both physical and psychological disability and handicap in employment. PMID- 11221275 TI - A validation study of the Siriraj Stroke Score. AB - A cross-sectional study was conducted on 160 Malaysian patients to validate the usefulness of the Siriraj Stroke Score (SSS) for differentiating intracerebral haemorrhage and infarction following acute strokes. Our results indicate that the score lacks sensitivity and specificity. It should thus not be used in epidemiological studies to determine stroke types in a community. More importantly, in the absence of information from neuroimaging of the brain, it cannot be used safely by physicians to assess the need or otherwise of thrombolytic and/or anticoagulant therapy after an acute stroke. PMID- 11221276 TI - The epidemiology of hysterectomy and irritable bowel syndrome in a UK population. AB - The prevalence of hysterectomy in the UK general population has not been previously reported. In addition, although it is known that many women with irritable bowel syndrome (IBS) have had a hysterectomy, the relationship between these two conditions has never been quantified. A random community sample of 2238 women aged 20-69 from Teesside was surveyed to determine the prevalence of hysterectomy and of IBS, the relationship between these and the influence of socioeconomic status and consultation behaviour on these variables. We analysed data from 1718 women, 13.6% of whom had a hysterectomy, 22.9% had IBS and neither condition was related to socioeconomic status. More women with IBS reported having had a hysterectomy than did non-sufferers, odds ratio 1.6 (1.1-2.2), p < 0.01; this association was also unaffected by socioeconomic status and was not fully explained by consultation behaviour. This is the first study to determine the prevalence of hysterectomy in a UK general population. The procedure is common and the excess of hysterectomy among women with IBS is considerable. Possible explanations include misdiagnosis of IBS resulting in hysterectomy, IBS symptoms occurring as a result of hysterectomy, a single underlying disorder which produces symptoms in both gastrointestinal and genitourinary tracts, or a combination of these factors. PMID- 11221277 TI - Are preoperative serum gastrin levels related to resectability and survival in gastric cancer? AB - The aim of this study was to determine the correlation between serum gastrin and resectability in patients with gastric cancer, and to see whether any difference could be demonstrated according to the histologic type and survival. Between 1994 and 1996 records of 34 consecutive patients with gastric carcinoma serum gastrin levels were measured and correlated with age, gender, lymph node positiveness, metastasis, Lauren's classification and survival. The mean serum gastrin level of patients was 98.38 pg/ml (normal range: 25-125 pg/ml). Twenty-six of 34 patients (76.5%) had normal gastrin levels and eight patients (23.5%) had high gastrin levels. Sixty-five per cent of patients with normogastrinaemia underwent resection with extended lymphadenectomy, while 38% patients with hypergastrinaemia underwent extended resection. All the hypergastrinaemic patients died within the first year, but in the normogastrinaemic group one, two and five-year survival rates were 39%, 23% and 4%, respectively. Even though these results are not statistically significantly different in regard to preoperative serum gastrin levels, we conclude that preoperative hypergastrinaemia is associated with unresectability and poor survival in patients with gastric cancer. PMID- 11221278 TI - An epidemiological study of falls on integrated general medical wards. AB - Reducing falls in hospital requires an environmental as well as a patient orientated approach. We studied patient and ward characteristics relating to falls in an acute setting. In a prospective open observational study, we examined fall characteristics in two nuclear designed wards (A and B) and a longitudinal ward (C). We recorded 63 falls among 1609 patients. Ward C had the most falls (31 vs 18/14; p = 0.01), fall positive days (29 vs 15/10; p = 0.002) and fallers (27 vs 13/12; p = 0.001; OR 2.54, CI--1.41-4.57). Ward C had a higher cumulative risk of falls (p = 0.006) and fall positive days (p = 0.003). Choice of ward was a significant independent risk factor for falls (p = 0.01) when controlled for age, sex, and diagnostic variation between the wards. Most falls were intrinsic (A 66.7%, B 64.2%, C 61.3%, p = 0.45). A significantly higher proportion of falls on ward C occurred by the bed (p = 0.04). Significant differences exist between the wards, and fall reduction programmes should identify and compensate for adverse ward-related factors to increase the effectiveness of patient-targeted fall risk assessments. PMID- 11221279 TI - Myocardial stunning and hibernation in clinical practice. AB - Myocardial stunning and hibernation are both clinically important causes of myocardial dysfunction and are caused by episodes of myocardial ischaemia. Stunning tends to occur acutely and may produce transient but clinically important reductions in left ventricular function in the setting of myocardial infarction, post coronary artery bypass grafting and even following episodes of effort induced angina. Hibernation refers to a chronic down-regulation of myocardial function in response to chronic myocardial ischaemia. Hibernating myocardium may be present in up to 50% of patients with significantly impaired left ventricular function and evidence of heart failure. Importantly, both these entities can be either prevented or ameliorated by preventing or lessening ischaemic burden. There is also evidence that there may be an overlap between these two entities and that hibernating myocardium may result from repeated episodes of myocardial ischaemia causing chronic stunning. PMID- 11221280 TI - Management of advanced breast cancer with endocrine therapy: the role of the primary healthcare team. AB - Of the 25,000 new cases of breast cancer annually in the UK, at least half will develop metastases at some time. Approximately one-third of these will be hormone sensitive and thus suitable for endocrine manipulation. Such patients may live for several years. Care should be patient-centred and evidence-based, with primary care playing an integral part in the multidisciplinary team. Quality of life is paramount, and largely determines decisions to change endocrine therapy. Tamoxifen remains the first choice treatment, but newer agents, in particular the oral aromatase inhibitors, have successfully extended the range of therapy available. Ovarian ablation can be effectively achieved using LHRH analogues, which have the advantage of being reversible if ineffective. In future, further improvements in outcome are likely with new pure antioestrogens and the possibility of sequential or combined use of existing drugs. PMID- 11221281 TI - Pharmacology and efficacy of eletriptan for the treatment of migraine attacks. AB - Sumatriptan, a 5-HT 1B/1D agonist, was introduced 10 years ago and was the most effective therapy for migraine attacks at that time. Eletriptan is a new 5-HT 1B/1D agonist with high potency and selectivity at 5-HT 1B/1D receptors. It is effective in animal models in which the vascular and neurogenic mechanisms implicated in migraine were measured. Eletriptan is selective for the intracranial blood vessels over other extracranial vasculature, in particular coronary arteries. Eletriptan has a rapid and complete oral absorption and a good oral bioavailability in migraineurs. In comparative trials 20 mg, 40 mg and 80 mg eletriptan, 100 mg sumatritpan and placebo were compared for the treatment of migraine attacks. All three doses of eletriptan were statistically superior to placebo for headache response and headache-free patients. The 80 mg dose of eletriptan was also superior to sumatriptan 100 mg. Headache recurrence, defined as return of moderate or severe headache within 24 hours of dosing and following a headache response at two hours after initial dosing, occurred in 33% of the patients following 100 mg sumatriptan and in 28%, 34% and 32% after 20 mg, 40 mg and 80 mg eletriptan. In another large trial, headache response rates were significantly higher for both doses of eletriptan (64% for 40 mg and 67% for 80 mg) than for two doses of sumatriptan (50% for 50 mg and 53% for 100 mg). Eletriptan 40 mg or 80 mg was also superior to ergotamine plus caffeine (Cafergot). In summary, eletriptan is a highly effective and fast-acting drug for the treatment of acute migraine attacks. PMID- 11221282 TI - Extracranial arterial aneurysms: a cause of crescendo transient ischaemic attacks. AB - Crescendo transient ischaemic attacks (TIAs) should be regarded as a medical emergency. Patients require hospitalisation with urgent assessment and symptom control with anticoagulant therapy. We report on three patients, all of whom had atherosclerotic aneurysmal disease of the extracranial arterial circulation who presented with crescendo TIAs. The possibility of extracranial aneurysmal disease should always be considered and excluded. PMID- 11221283 TI - The treatment of extracranial aneurysms of the carotid artery. PMID- 11221284 TI - Haemoglobin SC disease presenting with a compartment syndrome secondary to a deep vein thrombosis. AB - A patient presented with a deep vein thrombosis (DVT), which resulted in a compartment syndrome of both the thigh and the calf. Subsequently, the patient was found to have haemoglobin SC disease. Prompt fasciotomies were performed; however, some muscle and nerve damage was later clinically apparent. This case highlights the value of prompt diagnosis of compartment syndrome and the need for urgent formal fasciotomies. The case also demonstrates the value of seeking an underlying cause for a DVT when none is apparent. PMID- 11221285 TI - Solitary calcaneal metastasis in superficial bladder carcinoma. AB - We report a case of a solitary calcaneal metastasis in a patient with superficial bladder carcinoma. The patient underwent transurethral tumor resection twice because of local recurrence. Both histologic examinations revealed a grade 2 PT1 superficial transitional cell carcinoma of the bladder. The metastasis was detected four months after the initial cystoscopy, due to severe leg pain. The lesion was curetted and filled with bone cement. A year later, a below knee amputation was performed because of local recurrence. This case deserves special attention, for two reasons. First, metastatic carcinoma to the bones of the foot is very rare. Although bony metastasis by transitional cell carcinoma of the bladder can be seen, presenting as a symptomatic solitary lesion after superficial bladder carcinoma is extremely unusual. Second, failure to control bladder tumours by local means might be an indication for an early cystectomy, even in tumours with no evidence of muscle invasion, in order to prevent distant metastasis. PMID- 11221286 TI - Interferon treatment for thrombocytopenia associated with chronic HCV infection. AB - Thrombocytopenia is commonly seen in patients with chronic liver disease, due mainly to hypersplenism secondary to portal hypertension. We report a case of chronic hepatitis C admitted with thrombocytopenia of unknown cause. The patient s symptoms and platelet count improved markedly with interferon treatment. We conclude that interferon treatment in chronic C hepatitis may improve HCV-induced thrombocytopenia. PMID- 11221287 TI - Metastatic tumour of the tunica vaginalis testis from carcinoma of the stomach. AB - A 50-year-old man with advanced inoperable gastric adenocarcinoma and diffuse peritoneal metastasis received six cycles of palliative chemotherapy and responded clinically with weight gain. Two months after the completion of chemotherapy, however, he developed a left hydrocele. Aspiration yielded 70 ml of yellowish hydrocele fluid, which contained metastatic adenocarcinoma cells, consistent with a gastric primary tumour. A diagnosis of malignant hydrocele was made. Two weeks later, he developed a painful recurrent left hydrocele with increasing pain and swelling. Left orchidectomy was performed. Tiny white mural nodules measuring 1 mm in size were noted on the tunica vaginalis. No focal lesion was noted in the testis. On microscopic examination, the tunica vaginalis showed reactive mesothelial hyperplasia and extensive lymphatic permeation by poorly differentiated adenocarcinoma, consistent with a gastric primary tumour. PMID- 11221288 TI - Barnidipine: a step towards safer blood pressure control? PMID- 11221289 TI - Treatment of hypertension in the very old. AB - The objective of this study was to compare the long-term efficacy and safety of 6 months' treatment with barnidipine and hydrochlorothiazide (HCTZ) as monotherapy in patients aged > or = 75 years with mild to moderate essential hypertension. This was a randomised, double-blind, dose-titration study performed at 62 centres in 8 countries. A total of 397 patients were enrolled. Following a 4 week single blind placebo runin, 315 patients with a sitting diastolic blood pressure (SiDBP) of 95-115 mmHg and a systolic blood pressure of 150-200 mmHg were randomised to receive barnidipine 10 mg (n = 159) or HCTZ 12.5 mg (n = 155) once daily. In patients who had not responded (SiDBP > 90 mmHg) after 6 weeks of double-blind treatment, the dose was titrated upwards to barnidipine 20 mg or HCTZ 25 mg. After 18 weeks, those who did not respond to the higher dose had enalapril (up to 10 mg once daily) added to their regimen. Statistically equivalent reductions in SiDBP were achieved with barnidipine and HCTZ monotherapy. At week 18 of double blind treatment on monotherapy, 84% of patients in both groups were responders. The addition of enalapril in non-responders produced a further reduction in blood pressure. Both drugs were well tolerated. The incidence of drug-related adverse events was greater in the barnidipine than HCTZ-treated group but they were consistent with vasodilation and were categorised as mild to moderate. In conclusion, barnidipine and HCTZ are well tolerated and have equivalent long-term antihypertensive efficacy in older hypertensive patients. For patients whose blood pressure is inadequately controlled on monotherapy, combination therapy with enalapril is effective. PMID- 11221290 TI - Barnidipine, a long-acting slow onset calcium antagonist. AB - Barnidipine is a stereochemically pure dihydropyridine calcium antagonist with a high potency. The drug showed a slow onset and long-lasting vasorelaxating effect in vitro, and strong antihypertensive activity in hypertension models. Barnidipine was shown to have a high vasoselectivity and offered protection in cardiac and renal ischaemia models. The in vitro drug:drug interaction profile suggests a low potential for clinically relevant interactions with concomitant medication. It can be anticipated that barnidipine is an attractive calcium antagonist, offering good blood pressure control without compensatory baroreflex activity. PMID- 11221291 TI - The long-term efficacy and safety profile of barnidipine. AB - Two multicentre trials have investigated the efficacy and tolerability of treatment with once-daily barnidipine, in patients with mild to moderate essential hypertension. The long-term efficacy and safety of barnidipine were demonstrated in a long-term, multicentre, open-label study. In total, 106, 79 and 32 patients were followed for the first, second and third year, respectively. Patients received barnidipine at a dose titrated to achieve a sitting DBP > or = 90 mmHg or a decrease in sitting BDP > or = 10 mmHg. If necessary, another antihypertensive agent was added to achieve normalisation of blood pressure. In the first year, normalisation of blood pressure was achieved in 91% of patients. This was maintained in 91% and 81% of patients in the second and third years, respectively. At the end of treatment in both years, over 60% of patients remained on barnidipine monotherapy (10 or 20 mg/day). A low incidence of adverse events possibly or probably related to barnidipine (10 or 20 mg/day) monotherapy was reported in the first and second years with headache, peripheral oedema and palpitations the most commonly reported. In the third year of follow-up, only one adverse event, an ECG abnormality, was considered to be possibly related to the study medication. The effective 24 hour control of blood pressure with barnidipine monotherapy was confirmed in a randomised, double-blind, placebo controlled, cross-over study of 20 patients. These patients were given 6 week regimens of both barnidipine (20 mg/day) and placebo. Office and 24 hour ambulatory blood pressures were recorded at the end of each treatment phase. Barnidipine lowered blood pressure to a significantly greater extent than placebo both at night and during the day. Adverse events were classified as mild or moderate and fewer adverse events were reported with barnidipine treatment compared with placebo. Barnidipine monotherapy (20 mg/day) is safe and effective in providing 24 hour control of blood pressure. Furthermore, the efficacy and tolerability of barnidipine monotherapy (10 or 20 mg/day) are maintained for at least 2 years. PMID- 11221292 TI - Barnidipine monotherapy and combination therapy in older patients with essential hypertension: a long-term study. AB - The long-term (2 year) safety and efficacy of barnidipine was assessed in an open label, dose-titration, multicentre study of 236 patients aged > or = 75 years with a sitting diastolic blood pressure (DBP) > or = 95 mmHg. All eligible patients started treatment with barnidipine 10 mg once daily. After at least 4 weeks treatment, the dose of barnidipine was titrated upwards to 20 mg daily in patients who did not achieve normalisation of blood pressure (sitting DBP < 90 mmHg). After at least another 4 weeks of treatment an ACE inhibitor or diuretic was added if necessary. Barnidipine monotherapy was the final treatment in 74% of patients in the ITT population (50% barnidipine 10 mg, 24% barnidipine 20 mg). The overall response rate was 84.1% at endpoint. Overall mean sitting DBP decreased by 18.4 mmHg from 102.1 mmHg at baseline to 83.7 mmHg at endpoint. Although a total of 82.2% of patients reported at least one adverse event, only 37.4% of patients experienced an adverse event that was possibly or probably related to the study medication. Many patients experienced adverse events associated with co-existing diseases common in older people. It can be concluded that barnidipine as monotherapy or in combination with ACE inhibitors or diuretics is safe and effective in older patients with essential hypertension. PMID- 11221293 TI - Interaction profile and tolerability of barnidipine. AB - INTRODUCTION: Barnidipine is a new dihydropyridine calcium antagonist that is presented in modified-release capsules containing a single S-S optical isomer of the molecule. Its characteristics are of interest, as there is evidence of differences in kinetics, dynamics, interactions and safety of individual enantiomers in traditional racemic preparations of calcium antagonists. The safety of barnidipine and its interaction profile are reviewed. SAFETY: Adverse events with barnidipine are of mild to moderate intensity, most commonly of type I and occur in the early phase of treatment. Furthermore, safety results in elderly patients are comparable with those in the general population, indicating that barnidipine can be used without dose adjustment in elderly hypertensive patients. INTERACTIONS: Barnidipine has a pharmacokinetic interaction profile that compares favourably with those from other calcium antagonists. The pharmacokinetic properties of barnidipine are unaffected by food. Minor increases in its availability may occur with concomitant use of alcohol or grapefruit juice, but these are unlikely to have clinical relevance. In contrast with several other calcium antagonists, barnidipine does not affect the steady-state kinetics of digoxin, whereas, like other calcium antagonists its bioavailability may be increased by the concomitant administration of cimetidine. In addition, the potential of barnidipine and its major metabolites to affect the metabolism of concomitant medication is unlikely to be of clinical relevance. CONCLUSION: The interaction and tolerability profile of barnidipine is well established in all age groups. PMID- 11221294 TI - Hypertension guidelines and goals of treatment: role of calcium antagonists. PMID- 11221295 TI - Are there any relevant differences within the calcium antagonist class? PMID- 11221296 TI - ["One would say: a family"]. PMID- 11221297 TI - [Ethics of the isolation chamber]. PMID- 11221298 TI - [Community regulations and encounters]. PMID- 11221300 TI - [The unquantifiable--militarism of the past facing technocratical catechism]. PMID- 11221299 TI - [Violence, ultimate reaction to anxiety?]. PMID- 11221301 TI - [Fists and hands glued to the cigarette--2]. PMID- 11221302 TI - [The procedure of hospital admission]. PMID- 11221303 TI - ["Pain, physical or mental health?"]. PMID- 11221304 TI - [The law, rules and customs]. PMID- 11221305 TI - [Limits of the law, ethics]. PMID- 11221306 TI - Three approaches to use of questioning by clinical lecturers: a pilot study. AB - In the current health care climate nurses require very good problem solving and critical thinking skills. Questioning as a teaching strategy is viewed as one way to promote such student learning. Using a comparative descriptive quantitative and a qualitative approach, this pilot study investigated the types of questions asked of students by lecturers working within the preceptorship model in the clinical setting. A convenience sample of five volunteer nursing lecturers were tape recorded during their interactions with undergraduate students (n = 8). Initially two auditing approaches were used to analyse the interview data: relevant parts of Mogan and Warbinek's (1994) Observation of Nursing Teachers in Clinical Settings instrument (ONTICS Tool) and Craig and Page's (1981) conceptual framework as adapted by Sellappah, Hussey, Blackmore and McMurray (1998). The data were further analysed by qualitative content analysis. This study supported the findings of the ONTICS tool and Sellappah et al's framework that teachers asked predominantly directive style and low level questions. What the two approaches did not adequately capture was the complexity of the lecturers' questioning behaviours or the effects of contextual factors. The content analysis process however, identified three broad categories forming a model that effectively integrated aspects of the context of the lecturer/student interaction. It also represented lecturer questioning behaviours more comprehensively. The preliminary model offered has the potential to highlight the importance of lecturers asking questions that lead students to extend their thinking about practice. It could also contribute to student learning by assisting lecturers to understand the value and critical nature of their questioning and serve as a framework for staff development. PMID- 11221307 TI - Post-anaesthetic shaking. A review of the literature. AB - This paper describes the phenomenon of post-anaesthetic shaking (PAS) as it is discussed in the literature. Literature was obtained via computerised searches of the Cochrane Library, Medline, and Cumulative Index of Nursing and Allied Health Literature (CINAHL) databases. This review considers PAS in adults, who have had either a general or regional anaesthetic. It focuses on the controversy regarding the cause of the condition, the role of anaesthetics in hypothermia, pharmacological interventions, and non-pharmacological interventions. The key conclusion to emerge is that nurses must take patients' shaking seriously and initiate treatment for it. If PAS is associated with hypothermia then the patient needs to be rewarmed, and if it is associated with pain, analgesia needs to be administered. PMID- 11221308 TI - Am I dying nurse? AB - Tensions exist with regard to truth-telling about dying. Attitudes and opinions of doctors and nurses impact upon patients and their families. While traditionally doctors have assumed the role of telling patients and/or families, the nurse practitioner often has a closer relationship with the patient and may be the most appropriate person to answer the question "Am I dying?" If nurses accept they have a moral obligation to tell the truth then it is imperative that clinicians, researchers, educators, and the consumers of health services, deliberate on what truth-telling is. Cultural implications of both-truth telling and dying are little understood in New Zealand. The multi-cultural nature of New Zealand provides an opportunity for nurse researchers to address the many issues raised by the question "Am I dying, nurse?" PMID- 11221309 TI - Cultural safety/Kawa Whakaruruhau ten years on: a personal overview. PMID- 11221310 TI - Emergency departments and the inappropriate attender--is it time for a reconceptualisation of the role of primary care in emergency facilities? AB - The appropriateness of Emergency Department (ED) usage is often questioned, with recognition at an international level of the growing prevalence of 'inappropriate attenders'. This term is used to describe individuals who present for treatment that could more appropriately be provided in the primary health care setting. This is an issue of concern for staff working in New Zealand Emergency Departments. The present article offers a review of currently identified issues concerning ED attendance, and examines the core question of the role of primary care in the Emergency Department. It asks whether this is an appropriate use of ED resources, and if so, what are the implications for the role of the emergency nurse? PMID- 11221311 TI - The Workbook Portfolio: facilitating undergraduate student learning in the mental health clinical area. AB - Undergraduate nursing students are confronted with a multitude of challenges during their mental health clinical placements. Many of the required skills are dissimilar to other areas of nursing and students must also develop the cognitive skills that influence the behavioural ones. However, mental health and mental health nursing are influenced and determined by a complex, and sometimes contradictory, range of external influences. Such ambiguity can be confusing for even the most experienced practitioner, let alone an undergraduate student. This article describes the use of a model that has been developed to assist the student in tackling such complex issues. The Workbook Portfolio has identifiable components that encourage the development of reflective and analytical skills. Our article explains the workings of this model in a fashion that allows other educators to utilise it to benefit students in the mental health setting. PMID- 11221312 TI - The clinical performance of new degree graduates. AB - Since the transfer of nursing education from hospitals to tertiary institutions, debate regarding the competence of new graduates has continued. To date this issue has not been thoroughly researched. The lack of research related to the competence of degree graduates in New Zealand provided the impetus for this study, which was aimed toward identifying how graduates perceived their clinical performance during their first year of practice. A convenience sample of 30 graduates was surveyed after 3 months and 7 months in practice, using an adapted form of a questionnaire devised by Ryan and Hodson (1992). The results showed that over time, graduates generally required less direction in all areas of clinical competence. After 7 months in practice, the majority of the graduates rated their performance in nursing skills, communication skills, and professionalism at the expected level or above. However, some still required direction with using theory and research in practice, with meeting client's psychosocial needs and with teaching clients. In the leadership competency, after 7 months, most graduates saw themselves functioning at the expected level related to client care and needed less direction in unit management skills. However, many of the unit management skills were rated as 'not applicable' indicating that new graduates are not initially placed in a management role. Implications for nursing education and limitations of the research are discussed. PMID- 11221313 TI - Advanced nursing practice: experience, education and something else. AB - The purpose of this paper is to stimulate discussion and debate about the 'concept' of 'advanced practice' and the wider issue of 'advancing' nursing practice. Defining, credentialling and regulating advanced practice promises rich fruits for nursing. Advancing nursing practice will be a consequence only if the right conditions are fostered for the development and provision of nursing expertise in practice. A conscious and collective effort must be made to ensure that the expertise of all nurses is recognised and developed. One process which has shown promise in psychiatric and mental health nursing is 'clinical supervision'. Evolving nursing leadership roles and more education can provide only a partial solution to the problem of advanced and advancing practice. PMID- 11221314 TI - An emergency nurse's experience: David's story. PMID- 11221315 TI - Expert public health nursing practice: a complex tapestry. AB - The research outlined in this paper used Heideggerian phenomenology, as interpreted and utilised by Benner (1984) to examine the phenomenon of expert public health nursing practice within a New Zealand community health setting. Narrative interviews were conducted with eight identified expert practitioners who are currently practising in this speciality area. Data analysis led to the identification and description of themes which were supported by paradigm cases and exemplars. Four key themes were identified which captured the essence of the phenomenon of expert public health nursing practice as this was revealed in the practice of the research participants. The themes describe the finely tuned recognition and assessment skills demonstrated by these nurses; their ability to form, sustain and close relationships with clients over time; the skillful coaching undertaken with clients; and the way in which they coped with the dark side of their work with integrity and courage. It was recognised that neither the themes nor the various threads described within each theme exist in isolation from each other. Each theme is closely interrelated with others, and integrated into the complex tapestry of expert public health nursing practice that emerged in this study. Although the research findings supported much of what is reported in other published studies that have explored both expert and public health nursing practice, differences were apparent. This suggests that nurses should be cautious about using models or concepts developed in contexts that are often vastly different to the New Zealand nursing scene, without carefully evaluating their relevance. PMID- 11221316 TI - Clinical professorial appointments in nursing. PMID- 11221317 TI - Neonatal nurse practitioners--a model for expanding the boundaries of nursing culture in New Zealand. AB - The development and terminology of what constitutes advanced practice nursing roles in New Zealand has been the subject of recent debate within nursing. This article outlines the development of the neonatal nurse practitioner role in New Zealand as an example of one advanced practice nursing role. A model of how nursing culture changes to include roles that incorporate components that historically have been considered the domain of other health professionals is proposed. This article outlines some of the issues surrounding the neonatal nurse practitioner role, including the educational requirements for this role in New Zealand. PMID- 11221318 TI - Factors influencing health and well-being in the older adult. AB - Both in New Zealand and internationally there are increasing numbers of people living well into their senior years. Not only are more individuals reaching late adulthood, more are living beyond this stage. Because of corresponding increases in illness and/or disability this phenomenon has implications for the provision of health care to communities. This article offers a literature review of selected factors influencing the health and well-being of older people, with a particular emphasis on the older male. Implications for nursing practice in New Zealand are discussed. PMID- 11221319 TI - Women planning and experiencing pregnancy and childbirth: information needs and sources. AB - This paper reports the preliminary findings of a study of women planning a pregnancy and perinatal women with respect to their information needs and the sources of information they use. Fifty women, 7 planning a pregnancy, 30 pregnant and 13 postnatal, completed a questionnaire including questions about who they had approached for information about pregnancy issues, who had given them advice and why it was or was not useful, what they would currently like to know, and what they wished they had known during the previous three months. Results highlighted differences in the type of information provided by various sources: doctors and specialists were seen as primarily providing factual information; midwives also supplied information but more importantly gave reassurance and support; partners did not provide information but were valued for their support in a shared experience; and mothers and friends were primarily useful due to their own experiences. The findings also suggested the importance of information that is relevant to the women's current stage of pregnancy. PMID- 11221320 TI - Re-introducing Mavis Helena ('Pat') Paton. PMID- 11221321 TI - Are the 'faces scales' used to measure pain intensity in children comparable? PMID- 11221322 TI - Diet therapy--a forgotten art? AB - This study evaluated paediatric nursing students' knowledge of diet therapy to establish whether it was sufficient to prepare them for practice. A questionnaire sampled 19 1st-year and nine 4th-year students' diet therapy knowledge in relation to chronic renal failure, cystic fibrosis, juvenile diabetes mellitus and liver disease. The knowledge of 1st and 4th-year students was compared and then evaluated against criteria, devised by the researcher to measure whether this knowledge level was sufficient for practice. The Mann-Whitney Utest showed a significant difference between the 1st and 4th-years' diet therapy knowledge. The mean score for overall diet therapy knowledge of 4th-year students was 46 per cent. The results suggest that knowledge of diet therapy is insufficient to prepare nursing students for practice and that this topic needs further emphasis in paediatric nurse education. PMID- 11221323 TI - Mouth care for children with cancer. PMID- 11221324 TI - Do not resuscitate: critical incident reflection. PMID- 11221325 TI - Enteral feeding: practice guidance. PMID- 11221326 TI - Time to focus on practice. PMID- 11221327 TI - Basic infant life support: retention of knowledge and skill. AB - Successful resuscitation depends upon several factors including the underlying cause for the cardiac arrest and the availability of advanced life support. Another key factor is the ability of those first on the scene to administer basic life support. Knowledge and skills in basic life support were tested in six registered children's nurses, who were randomly chosen to take part in a small exploratory study. Knowledge was tested by means of a questionnaire and skill was tested with a practical test using an infant manikin. The Resuscitation Council (RC) (1997) guidelines were used as a guide. The results demonstrated that the knowledge and skills of those assessed were unsatisfactory, so a resuscitation update was arranged. The sample group was re-tested using the same questionnaire and practical test immediately following the resuscitation update and again six weeks later. Knowledge and skills improved in five of the six participants, although the order in which they were performing aspects of basic infant life support was beginning to alter by the six-week retest. PMID- 11221328 TI - Infant nutrition: Part Two. PMID- 11221329 TI - Reflection on practice: a student perspective. PMID- 11221330 TI - The future for nursing education: UKCC review has relevance for New Zealand. AB - The strategic review of undergraduate nursing education recently commissioned by the Nursing Council of New Zealand (NCNZ) will provide a focus for nursing education in Aotearoa/New Zealand in the immediate future. Recently the United Kingdom Central Council for Nursing, Midwifery and Health Visiting (UKCC) completed its own review of undergraduate nursing education. The published report 'Fitness for Practice', has many areas of relevance for New Zealand educators in outlining possible strategies for nursing education. Issues such as recruitment and access to education; retention; clinical assessment and placements; clinical skill acquisition and partnership are valid concerns for educators here also. Internationally the commonalties in issues of concern are remarkable and lend validity to the concept of the global village and the necessity for a global perspective in health care workforce planning, including educational preparation. Discussion of some of the recommendations informs nursing education of the possibilities for forward progress in these times of continual change in health care delivery systems. PMID- 11221331 TI - Quality in undergraduate nursing programmes: the role of Nursing Council. AB - This paper looks broadly at issues to do with quality monitoring in higher education and considers the role and focus of the Nursing Council of New Zealand in the approval of and ongoing monitoring of undergraduate nursing degree programmes. It is suggested that the approach taken by the Nursing Council is accountability-led where minimal attention is given to teaching and learning and actual graduate outcomes. This may lead to a mistaken belief that Nursing Council's monitoring focuses on quality or that the outcomes of their monitoring might contribute to programme enhancement. A shift to emphasise learning processes, students and continual improvement in order to enhance programme quality is proposed. PMID- 11221332 TI - Credentialing: setting standards for advanced nursing practice. AB - While the document Framework, Guidelines and Competencies for Post-Registration Nursing Education (Nursing Council of New Zealand, 1999) provides for approval of programmes preparing nurses for advanced practice, the related credentialing and titling of individual nurses in advanced practice has not been addressed. This article examines professional regulation with particular reference to advanced practice. As well as providing an overview of credentialing and other aspects of professional regulation, including licensure, certification, registration, and titling, the question of how much regulation, and by whom, will be explored. The paper has been prepared independently of the Nursing Council, and may not necessarily reflect the Council's views. PMID- 11221333 TI - The methodological journey of a grounded theorist: an interview with Denise Dignam. Interview by Lynne S. Giddings, Pamela J. Wood. AB - Nurses and midwives in Aotearoa/New Zealand are making a unique contribution to the development and application of various research approaches (methodologies) to nursing and midwifery practice. This is the first of a series of articles based on interviews with nursing and midwifery researchers, giving stories of their research journeys in relation to a particular methodology. The articles will give beginning researchers some real life examples of what it is like to carry out research. They are not in-depth explorations of the various methodologies. What we have attempted to capture is how real people actually use the various research methodologies we read about in textbooks and that frame the research which influences our practice. The stories are presented in interview format so that each interviewee's unique style and approach can emerge. The first researcher in our series is Denise Dignam (RGON, BA, DipSocSci) who in her PhD research is using a grounded theory approach to investigate issues related to breastfeeding. PMID- 11221334 TI - [Contemporary state and perspectives in neuroroentgenology]. PMID- 11221335 TI - [Diffusion-weighted image in the study of brain tumors and peritumoral edema]. AB - The informative value of the technique of diffusion-weighted images (DWI) and diffusion maps was studied in diagnosing supratentorial tumors of the brain. Sixty four patients were examined. Among them there were 35 patients with glial brain neoplasms of varying malignancy [benign astrocytomas (asc) in 15 patients, anaplastic asc in 10, and glioblastomas in 10)], 15 patients with meningiomas, 5 with hydrocephalus, 9 with cerebral circulatory disorders. To obtain DWI, diffusion-weighted echo-planar impulse sequence was used. ADC was within (1.52 +/ 0.34) x 10(-3) mm2/sec for fibrillary astrocytomes. The anaplastic astrocytoma group showed variations in ADC values: ADC was higher in the contrasted part of the tumor than in the non-contrasted one and averaged (1.23 +/- 0.32) x 10(-3) mm2/sec. Glioblastomas were also noted for a higher variation in ADC that averaged (1.18 +/- 0.29) x 10(-3) mm2/sec. Meningiomas had a greater MR signal in response to DWI and low ADC values [(0.97 +/- 0.17) x 10(-3) mm2/sec]. Particular emphasis is laid on the study of different types of brain edema. ADC in the area of vasogenic (peritumoral), cytotactic (ischemic), and interstitial edema was (1.30 +/- 0.11) x 10(-3), (1.04 +/- 0.05) x 10(-3), and (1.91 +/- 0.1) x 10(-3) mm2/sec, respectively (p < 0.05) and sharply distinct in ADC maps. PMID- 11221336 TI - [Proton magnetic resonance spectroscopy in diagnostics of tumorous and nontumorous lesions in brain]. AB - Whether proton magnetic resonance spectroscopy (1H-MRS) can be used in the diagnosis of tumorous and nontumorous lesions of the brain was studied. The results of studies were analyzed in 80 patients, including 54 patients with brain tumors (astrocytomas and meningiomas), 20 with nontumorous lesions of the brain, and 6 apparently healthy individuals (controls). The nontumorous lesions of the brain involved cerebral circulatory disorders as ischemia (n = 14) and postradiation changes (n = 6). The studies were performed on a 1.5-T Signa Horizont magnetic resonance tomograph by using the PROBE/SV programme package. The peak ratios of the following metabolites: N-acetylaspartate (NAA), choline (Cho), creatine, lactate (Lac), lipids (Lip) were examined in the spectra obtained. The spectra of astrocytomas showed a reduced peak of NAA, an elevated peak Cho; there was an increase in the peak of Lac along with higher tumor malignancy stage. The spectra of meningiomas presented a high peak of Cho along with a noticeable reduction in the peaks of other metabolites, the peak of NAA was not visualized. In ischemic lesion of the brain, the peak of Lac appeared within the first hours when the peaks of other metabolites were unchanged. A rise in the peak of Lac and a reduction in that of other metabolites were detectable with time. In radiation-induced lesions, the spectrum displayed a high peak of Lac and the peak of Lip appeared with virtually complete reduction in the peaks of other metabolites. 1H-MRS should be considered as an axillary technique used in combination with routine MRI in the diagnosis of various lesions of the brain, which can estimate chemical compositions, time-course of metabolic changes in the study tissue. PMID- 11221337 TI - [The use of chronic epidural electrostimulation of the spinal cord in children with spastic diplegia--a type of infantile cerebral palsy]. AB - The authors' first experience with spinal cord stimulation (SCS) at the lumbar level in the treatment of cerebral palsies (CP) in children aged 3-11 years who had lower spastic paraparesis of varying severity is presented. Complex clinical and physiological studies of all 9 children were made before and after surgery (follow-ups lasting 6-12 months). Preliminary results have indicated that the most significant changes occur primarily in pathological postural tonic reflexes. SCS has virtually no effect on fixed limb deformities, which requires further orthopedic surgical correction. A medical care schedule for CP children affected predominantly with lower spastic paraparesis should include, among its first priorities, electrode implantation for SCS. Due to the specific rehabilitative dynamics of motor functions, SCS should be made to treat these children before the deformities in the lower extremity joints get fixed. PMID- 11221338 TI - [Mapping of the motor-sensory cortex by functional magnetic resonance tomography in frontoparietal tumors]. AB - The potentialities of functional magnetic resonance imaging (FM-RI) in the preoperative mapping of the motor-sensory cortex of the brain in 24 patients with frontoparietal tumors and 5 healthy volunteers were studied. A good reproducibility of results was achieved while using a simple irritation paradigm as finger flexion-extension. The obtained activation maps were projected to the region of anterior and posterior central gyri and to the central sulcus. Imposition of the maps of motor-sensory cortical activation with routine T1 weighed images allows a surgeon to gain an insight into the mutual location of a tumor and a functionally significant portion of the cortex, by reducing the intraoperative risk of damage to this area. The intraoperative determination of the central sulcus by the evoked potential method in 4 patients confirmed the results obtained after FMRI. The relationship of the obtained activation maps to the presence of venous structures in the area concerned requires further studies on the modes of clarifying the site of functionally significant cortical areas in the brain. PMID- 11221339 TI - [The use of three-dimensional reconstruction in neuroroentgenology]. AB - The recent advent of spiral computed tomography (CT) and new fast impulse sequences in magnetic resonance imaging (MRI) into diagnostic practice has expanded the range of brain and spinal diseases detected by these techniques. This has also expanded the field of use of three-dimensional images obtained on the basis of mathematical algorithms for processing CT and MRI data. At present, not only neurotraumatology and maxillofacial surgery are the main areas in applying three-dimensional models. Spatial representation of bulky formations of the brain, their mutual location with the adjacent anatomic structures (with ventricles of the brain) may be useful in choosing a surgical access and in planning the scope of a surgical intervention. CT- and MR-angiographies that are now successfully used in diagnosing vascular pathology, providing high-solution angiograms not only can be competitive with direct angiography, but can replace this sophisticated study for vascular stenotic processes in the neck. Moreover, analyzing the internal surface of the vascular wall on the basis of virtual endoscopy may be useful in direct surgical and endovascular interventions. The purpose of this study was to pool long-term experience in using three-dimensional images in the qualitative improvement of diagnostic methods in examining neurosurgical patients and to define the most promising lines of their use in neurosurgery as a whole. PMID- 11221340 TI - [Diagnosis of cerebral arterial aneurysms in acute and subacute subarachnoid hemorrhage]. AB - The paper pools experience in using computed tomographic and magnetic resonance angiographies in patients with intracranial berry aneurysms in different periods following subarachnoid hemorrhage. The new low-invasive techniques for visualization of arterial vessels have been found to detect the aneurysm and to define its topographic and anatomic location in most cases (as high as 90%) by being on a par with direct cerebral angiography and to compare favourably with the latter. Based on the analysis of complex studies (angiography, CT- and MR angiographies), the authors have developed algorithms for diagnosing intracranial aneurysms by the stage of subarachnoid hemorrhage. PMID- 11221341 TI - [A study of the spinal fluid flow by magnetic resonance imaging]. AB - The study was undertaken to examine the potentialities of new MRI techniques (MR myelocysternoventriculography and phasic contrast-enhanced MRI with reference to a cardiac cycle) in visualizing the spinal fluid system and flow in different groups of neurosurgical patients. MR-myelocysternoventriculography was based on the sequences of SSFP-3D (Signa, GE, 1.5 T) and PSIF-3D (Magnetom 42SP, Siemens, 1.0 T). These regimens were applied to obtain highly T2*-weighed images. These techniques were used in 280 patients. Phasic contrast-enhanced MRI with reference to a cardiac cycle was performed in the axial (through the aqueduct of the cerebrum) and sagittal projects (CINE-2D mode, Signa GE). This technique was employed to study 30 patients and 5 healthy volunteers. MRI-cysternography based on SSFP-3D- and PSIF-3D sequences is recommended as the method of choice in evaluating the 3rd ventriculostoma and, in combination with spiral computed tomography, in detecting fistulas of the base of the skull. Phasic contrast enhanced MRI with reference to a cardiac cycle yielded the values of spinal fluid flow through the aqueduct of the cerebrum in health: Vsyst max = 4.1 +/- 1.3 cm/sec; Vsyst mean = 2.5 +/- 1.4 cm/sec; Vdiast max = 3.4 +/- 1.5 cm/sec; Vdist mean = 2.5 +/- 1.7 cm/sec (N = 5). The prospect of the technique is to develop recommendations and to predict prognosis while making bypass surgery for ventriculostomas and cystostomas. PMID- 11221342 TI - [Calcified giant aneurysm of the middle cerebral artery]. AB - A rare case of calcified giant aneurysm of the middle cerebral artery is presented. This is a 28-year-old female with seizures and right-sided hemiparesis in whom plain scull films and computed tomography revealed a large calcified lesion (measuring 7.5 x 5.5 x 4.5 cm) of the left cerebral hemisphere. The lesion was removed by the pterional transsylvian approach and found to be a calcified giant thrombotic aneurysm of the middle cerebral artery. The CT characteristics of these rare lesions and the success of surgery in this case are briefly discussed. PMID- 11221345 TI - [Rumania, a potential mine of economic crisis]. PMID- 11221346 TI - [For a liberal public health medicine]. PMID- 11221344 TI - [The new pathogenetic treatment of cervical dystonia: rationale, methods, outcomes]. AB - The paper presents data obtained from studies of the impact of the otolithic apparatus of the inner ear on the degree of symptoms of cervical dystonia. The findings make it possible to substantiate a pathogenetic treatment of this disease, which involves intratimpanal unilateral injection of the vestibulotoxic antibiotic streptomycin. The results achieved and the mechanisms of the therapeutical effect observed are discussed. PMID- 11221343 TI - [Recovery of the spinal function: current potentialities and research prospects]. PMID- 11221347 TI - [Nursing ethics and practice in oncology]. PMID- 11221348 TI - [Patients with enterostomy, nurses: a good ensemble]. PMID- 11221349 TI - [Nutrition and cancer]. PMID- 11221350 TI - [Nursing care of patients with chronic terminal renal insufficiency]. PMID- 11221351 TI - [Cultivating our specificity, let us be autonomous and organized]. PMID- 11221352 TI - [IRCT (chronic terminal renal insufficiency) needs anal treatment strategies]. PMID- 11221353 TI - [Hemodialysis method and nursing care]. PMID- 11221354 TI - [Hemodialysis equipment]. PMID- 11221355 TI - [Methodologic guide to controlling water]. PMID- 11221356 TI - [Nursing strategy: concerning hemodialysis]. PMID- 11221357 TI - [Peritoneal dialysis, method, education, role of the nurse]. PMID- 11221358 TI - [Controlling pain in renal transplantation]. PMID- 11221360 TI - [Albania, to get out of a perverted health care system]. PMID- 11221359 TI - [Safety of injections]. PMID- 11221361 TI - [Government policy about drugs]. PMID- 11221362 TI - [End of life, euthanasia or palliative care?]. PMID- 11221363 TI - [What kind of death do we desire?]. PMID- 11221364 TI - [An astonishing report of the CCNE (National Ethics Committee]. PMID- 11221365 TI - [For or against exceptional euthanasia]. PMID- 11221366 TI - [Decisions concerning end of life, euthanasia questioned]. PMID- 11221367 TI - [How to respond to demands of euthanasia?]. PMID- 11221368 TI - [New aspects in drug therapy of ocular allergies]. AB - Ophthalmic allergoses belong to highly prevalent ocular diseases. According to the records of the first center of allergic diseases of the eye set up in 1971 at Helmholtz Institute of Ocular Diseases in Moscow, the most prevalent clinical forms are seasonal pollenosis conjunctivitis, drug allergies, spring keratoconjunctivitis, large-papillary conjunctivitis, chronic allergic conjunctivitis, allergy associated with the "dry eye" syndrome, atopic keratoconjunctivitis, and ocular involvement in systemic immune diseases. Therapy of ocular allergies is based on the three main principles: removal of the allergen responsible for disease, immunotherapy, and symptomatic drug therapy. The main agents used in local antiallergic therapy are antihistaminic drugs (antasoline and acelastin), drugs inhibiting mast cell degranulation (chromoglycates and lodoxamide), and accessory drugs: corticosteroids (dexamethasone and deosonide), nonsteroid antiinflammatory agents (diclofenak), immunosuppressants (cyclosporin), and vasoconstrictors (tetrisoline). Antiallergic drugs can be used as monotherapy or in combinations, as they differ by the mechanism of action. Antiallergic drugs are used with good results in combined therapy of infectious conjunctivitis and keratitis. PMID- 11221369 TI - [New aspects in the problem of retinal and optic nerve diseases]. AB - Main trends in research and practical activities of Department of Retinal and Optic Nerve Diseases of Moscow Helmholtz Institute of Ocular Diseases are reviewed: vascular, inflammatory, and dystrophic diseases of the retina, choroid, and optic nerve, results of recent studies of the pathogenesis, diagnosis, and treatment of diabetic retinopathies, vascular abnormalities, uveitis, diseases of the optic nerve, and hereditary diseases of the retina are presented. Problems in surgical treatment of diseases of the retina and vascular tract and complications thereof are discussed. PMID- 11221370 TI - [The concept of ophthalmologic oncology development]. AB - The authors review the research results concerning the diagnosis and treatment of ocular tumors over 25 years of activities of Department of Ophthalmooncology and Radiology and analyze the perspective trends for future studies. PMID- 11221371 TI - [Clinical picture and treatment of diplopia]. AB - A total of 203 patients with stable binocular diplopia were observed. Examinations included coordimetry, analysis of double images, and investigation of the doubling field in the gaze field. All examinations were performed using an original method with a serial computer. The treatment included therapy of the underlying disease, choice of correcting prisms, exercises aimed at extension of separate vision field, and operation on the oculomotor muscles. Three main forms of diplopia were distinguished: 1) muscular; 2) sensory; and 3) mixed. The first form includes diplopias in paresis of n.III and n.IV, n.VI, late development of convergent squint, orbital injuries, endocrine ophthalmopathy, and myasthenia. The second form includes diplopias developing after delayed operations for convergent squint, and the third form are diplopias after operations for detachment of the retina and implantation of intraocular lenses. The treatment led to complete neutralization of doubling in 18.7% cases, neutralization in the main part of the gaze field in 53.7%, the same with prism correction in 12.8% cases; in 14.8% patients adaptation to diplopia was attained after suppression of the second image. Diplopia in late squint is prognostically the most favorable, and the following conditions are listed in the order of more or less good prognosis: paresis of n.VI, n.IV, orbital injuries, endocrine ophthalmopathy, and artiphakia. The least favorable prognoses are for patients after delayed operation for squint and detachment of the retina. A new operation, plastic repair of the external m. rectus, was used in 96 patients with pareses of n.VI; no compensation was attained in only 2 patients. PMID- 11221372 TI - [Ultrasound in ophthalmology]. AB - Research activities of Department of Ultrasound are carried out in cooperation with other departments of the institute. This paper sums up 30-year activities of the department on the utilization of ultrasound in ophthalmology with diagnostic and therapeutic purposes. Ultrasound is a highly informative diagnostic and effective treatment modality in various ocular diseases. PMID- 11221373 TI - [Pathogenetic factors of destructive process in trabecular tissues in primary open-angle glaucoma]. AB - Trabecular endothelium and collagen fibers of the posterior wall of Schlemm's channel, obtained in sinusotrabeculectomy from patients with various stages of primary open-angle glaucoma were examined by electron microscopic and biochemical methods. Endothelial cell destruction, damage, rejection, and dissociation in intertrabecular space, progressing in severity, were observed. "Denudation" and degradation of collagen fibers and fibrils were observed. The content of lipid peroxides in aqueous humor and blocks of Schlemm's channel trabecular wall increased from stage to stage, while the level of biogenic antioxidant glutathione decreased. PMID- 11221374 TI - [Remote results of proxopheline therapy of patients with primary open-angle glaucoma]. AB - Effects of an original Russian combined preparation proxofelin, consisting of 1% proxodolol and 0.25% clofelin solutions, on intraocular pressure (IOP), hydrodynamics, ocular function, arterial pressure, and heart rate have been evaluated in 42 patients (59 eyes) with primary open-angle glaucoma for up to 2 years. Examinations were carried out before proxofelin therapy and after 6, 12, 18, and 24 months of regular therapy (twice a day). Pronounced hypotensive effect on IOP (10.0 +/- 0.3-11.2 +/- 0.2 mm Hg) was due to a significant increase (p < 0.01) in the discharge easiness coefficient (by 50-77% in comparison with the initial value) and suppressed production of aqueous humor (by 40-50% of the initial level). Visual acuity did not change, visual field was significantly (p < 0.05) extended during all terms of examinations, changes in arterial pressure and heart rate during long-term therapy were negligible. The hypotensive effect of proxofelin was insufficient in 20% patients; in such cases its combination with pilocarpin was effective. In the rest patients tolerant IOP was attained by instillations of the monopreparation. Hence, proxofelin is an effective drug for treating primary open-angle glaucoma; its efficiency is apparently due to its hypotensive action. PMID- 11221375 TI - [Effect of therapy with blood component (activated autoplasma) on blood glutathione level in patients with vascular abnormalities on the fundus oculi]. AB - Thirty-three patients with central chorioretinal dystrophy, 18 with proliferative diabetic retinopathy, and 15 controls without ocular diseases were examined. All patients were treated by blood components. The treatment started with activation of blood plasma platelets. Glutathione was measured in two portions of plasma: intact and containing platelet activation products. The content of glutathione was higher in activated autoplasma of 21 patients with central chorioretinal dystrophy and 6 patients with diabetic retinopathy than in intact plasma by 107 and 72%, respectively. A decrease in glutathione level in activated autoplasma was observed in 1 patient with central chorioretinal dystrophy and in 9 with diabetic retinopathy. Hence, antioxidant defense is decreased in diabetic retinopathy, since glutathione is involved in reduction of organic hydroperoxides. PMID- 11221376 TI - [Moscow Gel'mgol'ts Institute of Ocular Diseases: the past and present]. PMID- 11221378 TI - [Efficiency of detection and preventive treatment of retinopathy in premature neonates]. AB - A total of 580 preterm babies born weighing 540-2500 g at terms less than 35 weeks were examined. The mean incidence of neonatal retinopathy under standard conditions of care in Moscow is 26%. The incidence of disease depends on body weight at birth and term of gestation. Risk factors conducive to the development of neonatal retinopathy are maternal diseases (gestosis, chronic somatic and gynecological diseases, hemorrhages in labor, detachment of placenta), and diseases of babies other than low body weight at birth and those due to preterm delivery (bronchopulmonary dysplasia, periventricular leukomalacia, intragastric hemorrhages, severe infection, early anemia, periods of hypercapnia and long oxygen therapy). The disease spontaneously regressed in 78% babies with stages I II. In 32 (22%) babies the condition progressed to stage III. Preventive cryocoagulation was performed in 24 babies (48 eyes). The efficiency of preventive treatment is 70.4% and depends on the disease pattern. Cooperation of neonatologists and ophthalmologists essentially improves the diagnosis and prevention of severe forms of retinopathy neonatorum. PMID- 11221377 TI - [Experimental validation of licopin-containing drug tomatol use in combined therapy of patients with diabetic retinopathy]. AB - Effects of tomatol on metabolic changes in the blood and lacrimal fluid and ocular capillaries of rabbits with alloxane diabetes were studied. Tomatol is a drug containing licopin carotenoid characterized by a high biological activity. The intensity of lipid peroxidation was notably decreased, antioxidant activity of the blood increased, lipid metabolism parameters in the blood and some parameters of proteinase inhibitory balance in the blood and lacrimal fluid normalized in diabetic rabbits treated with tomatol in comparison with untreated rabbits. Changes in perilimbic capillaries were less expressed in treated vs. untreated animals. Hence, tomatol is recommended for combined therapy of patients with diabetes as a drug normalizing metabolism and probably decelerating the development of diabetic retinopathy. PMID- 11221379 TI - [Sympathetic ophthalmia as an autoimmune disease]. AB - Discusses published reports and one's own findings indicating that sympathetic ophthalmia can be regarded as an autoimmune disease. PMID- 11221381 TI - [Scleroplasty with plasma-modified homoslceral grafts: experimental morphological study]. AB - Healing of homoscleral grafts treated by gas discharge low-temperature plasma has been studied. Such treatment leads to formation of a modified surface layer in scleral tissue; the presence of such a layer improves the hydrophilic properties and biocompatibility of the sclera, thus promoting better adaptation of the graft to further restructuring and healing during the postoperative period. Experiments on 32 eyes of chinchilla rabbits showed that after scleroplasty with thus treated transplants, complete replacement of fibroblasts and collagen carcass of the graft was observed as early as after 7.5 months (vs. 12 months in the control); the graft was stabilized and tightly grown into the sclera to form a solid sclera graft complex which fortifies the scleral membrane of the eye. Use of plasma modified transplants may improve the efficiency of scleroplastic operations in progressive myopia and ocular injuries. PMID- 11221380 TI - [Diagnosis, immunopathogenesis, clinical picture and treatment of uveitis in nephropathies]. AB - Complex clinical and immunological studies in 39 patients with uveitis and a history of nephropathies disclosed a relationship between renal diseases and vascular tract of the eyes. Specific features in the clinical symptomatology and immunological disorders were detected. Anterior and generalized forms, bilateral involvement, Tyndall's symptom, combined vitreolenticular changes, often with the exudative hemorrhagic component, predominated in the clinical picture of uveitis in patients with nephropathies. Uveitis ran a protracted course resistant to therapy, with frequent relapses. The disease occurred mainly in women. Predominant disorders in immunopathogenesis were disorders in the complex formation system. Uveitis in patients with nephropathies should be treated with due consideration for the etiology of nephropathy, clinical course of uveitis, and immunological disorders. Diseases of the vascular tract associated with nephropathy are rare in the etiological structure of uveitis and retinovasculitis (3.24%). PMID- 11221382 TI - [Postradiation atrophy of anophthalmic orbit after treatment of retinoblastoma. System of surgical rehabilitation]. AB - A system of surgical treatment of patients with radiation atrophy of orbital tissues has been developed in order to attain a stable position of the prosthesis in the cavity and improve the patients' appearances. A total of 366 interventions were performed in 242 patients. The operations were as follows: formation of conjunctival cavity by autotransplants of the mucosa from the lips (242), delayed plasty of the stump (81), contour plasty of the temple and external edge of the orbit (32), correction of eyelids (11). Single-stage treatment was carried out in 156 patients and 2-7 stages in 86 patients. Positive results were attained in all cases: the depth of the vault increased, lagophthalmos decreased, falling-in defect of prosthesis, eyelids, and temple were reduced, and stable position of the prosthesis in the cavity was attained. Surgical treatment of this condition differs greatly from plastic repair for other diseases because of changes in tissues after radiotherapy. Functional and cosmetic rehabilitation of patients with postradiation atrophy of orbital tissues after treatment of retinoblastoma with good effect can be attained only by staged surgical treatment. PMID- 11221383 TI - [Computer method for evaluating disorders in sense of color]. AB - A new method for evaluating disorders in the sense of color has been developed and offered for practice. A total of 340 patients with diseases of the retina and optic nerve and 80 normal subjects were examined. The results indicate that different conditions of examination, selection of combination by the color, brightness, and deepness of the stimulus and background allow detection of decreased sensitivity of one, two, or three color perceptors (disorders in sense of color--color blindness) and permit a quantitative evaluation of functional disorders in the color channels of visual system. The new method can be used in the diagnosis of the initial pathological processes of different origin, involving the cone system at any level of visual route and associated with acquired disorders in color vision. PMID- 11221384 TI - [Department of Traumatology, Reconstructive and Plastic Surgery and Ocular prosthetics, Gel'mgol'ts Moscow Institute of Ocular Diseases: four recent decades]. AB - Main trends in research and practical activities of the department are reviewed: treatment of injuries, removal of foreign bodies, introduction of new microsurgical technologies and equipment, development of reconstructive laser operations, development of concept of pathogenesis of burn disease, and ophthalmoplasty. PMID- 11221385 TI - [Prevalence and clinical significance of active cytomegalovirus infection in patients with inflammatory ophthalmopathy]. AB - A total of 374 patients with different inflammatory diseases of the eyes were examined (227 children and 147 adults). For detecting active cytomegalovirus (CMV) infection, sera were tested for antibodies to nonstructural intact CMV proteins. Antibodies were detected in 26 of 147 adults (17.7%) and 15 of 227 children (6.6%). Difference in the frequency of detection of active CMV infection in adults and children is statistically significant (p < 0.01). Three groups of patients with active CMV were distinguished: children with congenital diseases, immunocompromised patients, and the most numerous group of patients with isolated ocular diseases without manifest signs of immunodepression. In this latter group active CMV was detected in patients with different clinical diagnoses, including ophthalmic herpes. Russian commercial enzyme immunoassay kit CMV-Control proved to be a highly sensitive, simple, and cheap test for the diagnosis of exacerbations of chronic CMV infection. PMID- 11221386 TI - [Significance of lacrimal fluid peroxidation and anti-radical defense parameters for prediction and treatment of complicated myopia]. AB - Study of lipid peroxidation and antiradical defense parameters in the lacrimal fluid from 270 eyes of children and adolescents with progressive myopia demonstrated a relationship between the development of peripheral vitreochorioretinal dystrophies and imbalance between antioxidant activity (AOA) of lacrimal fluid and intensity of radical formation evaluated by chemiluminescence (CL) intensity. The AOA/CL ratio is proposed as a reliable indicator for predicting the course of progressive myopia. A value < 30 indicates poor level of antioxidant defense of ocular media and tissues and is a prognostically unfavorable sign as regards development of peripheral vitreochorioretinal dystrophy. A local antioxidant remedy has been developed and clinically tried for preventing and treating complicated myopia: ocular medicinal films with emoxipin and pyridoxine hydrochloride. PMID- 11221387 TI - [Refractory glaucoma: peculiarities of treatment]. AB - Refractory glaucoma is a clinical variety of glaucoma remarkable for its resistance to therapy. This determined special approaches to choice of drugs and methods ensuring a stable hypotensive effect as one of the conditions of preserving the visual functions. Original methods for surgical treatment of refractory glaucoma are proposed. New effective operations prevent excessive cicatrices at the site of intervention, one of the major causes of failure of antiglaucoma operations. Ultrasonic cyclodialysis is an effective method for surgical treatment of glaucoma in an aphakic eye. A principally new approach to treatment of refractory glaucoma is based on the use of high-frequency focussed ultrasound, a noninvasive method (sclerocyclodestruction) for attaining the hypotensive effect. The efficiency of the natural cytokine complex in the treatment of refractory glaucoma is due to effects of immunopeptides on repair processes at the site of intervention, which inhibit cell growth and prevent excessive development of cicatricial tissue round newly created routes of humor discharge. PMID- 11221388 TI - A vision of how ethical and clinical knowledge articulate in the effort to serve patients better. PMID- 11221389 TI - Ethics and education. AB - In the debate concerning the education of nurses that is currently taking place in Denmark, two widely differing views are apparent regarding the best way of training nurses such that the ethical aspect of their work is adequately considered. The first of these is based on the premise that practical care is fundamental to and justified by theories on nursing, care and ethics, which is why the theoretical part of nurse education deserves a higher priority. The second view is based on the premise that social care cannot be taught by means of theories, but can be learnt only through practice. The master-apprentice principle of ancient Greece is stressed in connection with this as being a viable alternative to the theoretical model of education. These two very different views can be traced back to Plato's and Aristotle's ideas on ethics and teaching respectively; indeed, those engaged in the debate make specific reference to these philosophers. In Denmark, a third fundamental viewpoint exists, known as 'ontological ethics'. Phenomenologist KE Logstrup is one of the best-known representatives of this view. Basing the line of argument on Logstrup's ethics and the view of education associated with this, this article questions the relevance of ancient Greek thought to today's world by illustrating a number of problems that are connected with the theoretical model of nurse education and with the master-apprentice principle. Logstrup associates ethics with the aesthetic principle that 'the useless is the most useful' in human life and with the view we also see in Kierkegaard's and NFS Grundtvig's writings that ethics can be imparted only by indirect means. Logstrup bases his understanding of ethics on the Judaeo-Christian concept of Genesis and the view that human beings were created with an ethical potential that is best nourished by aesthetic impressions. PMID- 11221390 TI - A socratic dialogue on the question 'what is love in nursing? AB - It is the thesis of the authors that the caring ethic and moral state of being of nurses ideally suffuses their professional caring and is thus implicit in their ethical decision making. Socratic dialogue is a technique that allows such moral attitudes to be made explicit. This article describes a Socratic dialogue conducted with nurses on the topic: 'What is love in nursing?' The conclusions drawn were based on the belief that the current western-style health care system restricts the practice of nursing in such a way as to limit professional caring and loving possibilities. Nurses who love in the practice of caring go beyond the role definition of the duty of care; they are people who are prepared to think differently about their practice as professionals, and are identified as competent risk takers committed to the betterment of the other. From this dialogue, 'love in nursing' was understood as the willingness and commitment of the nurse to want the good of the other before the self, without reciprocity. PMID- 11221391 TI - An African ethic for nursing? AB - This article derives from a doctoral thesis in which a particular discourse was used as a 'paradigm case'. From this discourse an ethic set within a South African culture arose. Using many cultural 'voices' to aid the understanding of this narrative, the ethic shows that one can build on both a 'justice' and a 'care' ethic. With further development based on African culture one can take the ethic of care deeper and reveal 'layers of understanding'. Care, together with compassion, forms the foundation of morality. Nursing ethics has followed particular western moral philosophers. Often nursing ethics has been taught along the lines of Kohlberg's theory of morality, with its emphasis on rules, rights, duties and general obligations. These principles were universalistic, masculine and noncontextual. However, there is a new ethical movement among Thomist philosophers along the lines to be expounded in this article. Nurses such as Benner, Bevis, Dunlop, Fry and Gadow--to name but a few--have welcomed the concept of an 'ethic of care'. Gilligan's work gave a feminist view and situated ethics in the everyday aspects of responsiveness, responsibility, context and concern. Shutte's search for a 'philosophy for Africa' has resulted in finding similarities in Setiloane and in Senghor with those of Thomist philosophers. Using this African philosophy and a research participant's narrative, an African ethic evolves out of the African proverb: 'A person is a person through other persons', or its alternative rendering: 'I am because we are: we are because I am.' This hermeneutic narrative reveals 'the way affect imbues activity with ethical meaning' within the context of a black nursing sister in a rural South African hospital. It expands upon the above proverb and incorporates the South African constitutional idea of 'Ubuntu' (compassion and justice or humanness). PMID- 11221392 TI - The experiences of elderly people in geriatric care with special reference to integrity. AB - The aim of this study was to obtain an increased understanding of the experiences of elderly people in geriatric care, with special reference to integrity. Data were collected through qualitative interviews with elderly people and, in order to obtain a description of caregivers' integrity-promoting or non-promoting behaviours, participant observations and qualitative interviews with nursing students were undertaken. Earlier studies on the integrity of elderly people mainly concentrated on their personal and territorial space, so Kihlgren and Thorsen opened up the possibility of considering the concept of integrity from a broader view by recognizing its relationship to the larger framework of the self concept. Based on this, findings in the present study indicate that elderly people's integrity relating to their corporal self were the least violated. On the other hand, their psychological, information and cultural selves were the most exposed. The study also identified a further dimension (i.e. one relating to social self), which should be included in the concept of integrity because respecting elderly people's social self reduces their feelings of loneliness, isolation and seclusion. In summary, the results indicate that the concept of integrity is complex and has several dimensions. PMID- 11221393 TI - Moral sensitivity: some differences between nurses and physicians. AB - We report the results of an investigation of nurses' and physicians' sensitivity to ethical dimensions of clinical practice. The sample consisted of 113 physicians working in general medical settings, 665 psychiatrists, 150 nurses working in general medical settings, and 145 nurses working in psychiatry. The instrument used was the Moral Sensitivity Questionnaire (MSQ), a self-reporting Likert-type questionnaire consisting of 30 assumptions related to moral sensitivity in health care practice. Each of these assumptions was categorized into a theoretical dimension of moral sensitivity: relational orientation, structuring moral meaning, expressing benevolence, modifying autonomy, experiencing moral conflict, and following the rules. Significant differences in responses were found between health care professionals from general medical settings and those working in psychiatry. The former agreed to a greater extent with the assumptions in the categories 'meaning' and 'autonomy' and to a lesser degree with the categories 'benevolence' and 'conflict'. Moreover, those from the psychiatric sector agreed to a greater extent to the use of coercion if necessary. Significant differences were also found for some of the MSQ categories, between physicians and nurses, and between males and females. PMID- 11221394 TI - Improving the quality of clinical practice. PMID- 11221395 TI - Patients in persistent vegetative state ... and what of their relatives? PMID- 11221396 TI - Speed kills: amphetamines, children and nurses. PMID- 11221397 TI - Withdrawing or withholding artificial hydration and nutrition. PMID- 11221398 TI - Determination of moral negligence in the context of the undermedication of pain by nurses. AB - The problem of undermedication of pain in health care is widely recognized and acknowledged; however, there is an obvious lack of exploration of this problem from an ethical perspective. When undermedication is raised as a moral concern, the underlying premise is that a patient may experience harm or not benefit from ineffective pain management practices. I will argue that the harm is of a particular type, that is, moral negligence. My intention is to increase nurses' awareness of both the type of moral harm they are causing, and their professional and moral duties to provide appropriate medication, more particularly to avoid undermedication. I hope that this heightened awareness will be incorporated into practice. As a nurse, I chose to focus on nursing for this article, but my claims are applicable to other health professions, such as medicine. PMID- 11221399 TI - Ethical implications of pain management in a nursing home: a discussion. AB - Pain is the most frequently communicated complaint among elderly people. Discussion of the ethics of pain management in nursing home residents has not appeared in the literature. The purpose of this article is to present an ethically-based pain management action plan for elderly nursing home residents. Nurses empowered with the latest information and cognizant and comfortable with their own views about pain are likely to effectuate a positive patient outcome. Further research will add to the current knowledge base while laying the groundwork for new interventions. PMID- 11221400 TI - The attitude of Canadian nurses towards advance directives. AB - This article seeks to shed light on the beliefs that influence nurses' intention of respecting or not respecting an advance directive document, namely a living will or a durable power of attorney. Nurses' beliefs were measured using a 44 statement questionnaire. The sample was made up of 306 nurses working either in a long-term care centre or in a hospital centre offering general and specialized care in the province of Quebec. The results indicate that nurses have a strong intention of complying with advance directives written by patients. The analysis also shows that four variables determine the strength of this intention: respect for autonomy; the location of the workplace; justice; and the dimension of relationships and emotions. Although these documents favour the expression of patients' wishes, nurses should be aware that they do not systematically guarantee respect of a patient's autonomy, nor do they replace a relationship based on trust between patients and health care professionals. PMID- 11221401 TI - Policy implications of the biological model of mental disorder. AB - The current dominant paradigm of mental disorder is that psychopathology is a deviation from normal physiological functioning of the brain. This paradigm is closely allied to the identity theory of mind in philosophy, which holds that mental phenomena are identical with the physical state of the brain. The assumptions of the biological model have policy implications, regardless of the utility or 'truth' of the paradigm, which should be made explicit for the assessment of ethics in mental health policy formulation. The nature of mental phenomena has been debated throughout history, without consensus. Several critiques of the biological model are offered to encourage enquiring scepticism. The policy implications discussed are political conservatism, broadened rationales for forced treatment, utility in managed care, and the use of medical necessity criteria to allocate treatment. PMID- 11221402 TI - Ethical issues in public health nursing. AB - This qualitative study was designed to explore ethical issues in public health nursing in the Canadian context, and to begin to identify strategies to support ethical practice. Twenty-two public health nurses, 11 in rural and 11 in urban settings, were asked to describe ethical problems they had experienced in the course of their work. These participants most often described situations that required a relational response rather than an active choice between options. Their goal was to optimize the good, while at the same time maintaining a supportive relationship. Analysis revealed five interrelated themes, each with several subthemes: relationships with health care professionals; systems issues; character of relationships; respect for persons; and putting self at risk. It was clear that all aspects of public health nursing have ethical components. PMID- 11221403 TI - The Helsinki Declaration: why all the fuss? AB - Since 1964, the Declaration of Helsinki has been accepted internationally as the cornerstone for research ethics. As such it has been incorporated into a number of guidance documents for research undertaken on human subjects. In 1999, the American Medical Association put forward a proposal for wide-ranging revision of the document, which would significantly weaken the rights of research subjects and lower the standards for research on human subjects. This article discusses the probable effects of the most significant proposals for change and argues against them. It also urges nurses, especially those involved in research, to become involved in the international consultation currently being undertaken by the World Medical Association. PMID- 11221404 TI - Case study. The right to die? PMID- 11221405 TI - Scientifically-based clinical practice guidelines or best practices. PMID- 11221406 TI - An ethical insight into nursing research in Turkey. AB - Scientific and technological improvements are accomplished only because of much research. The increase in the number of research studies causes a rise in ethical problems. Nursing research is no exception to this. The aim of this study is to identify and analyse ethical problems in nursing studies. This research is descriptive and partly analytical. It is retrospective in the sense that 169 Master of Science and 66 doctoral theses written between 1972 and 1998 in the Department of Nursing, Institute of Health Sciences, Hacettepe University, Ankara, Turkey, were examined. The following ethical rules were used as criteria: that no harm should be caused to the subject; the subject was informed about the research topic; permission was obtained from the subject; and the privacy of the subject was maintained. The evaluation was carried out by distributing the theses among background variables and by employing nonparametric tests. The research associated with the theses was not harmful to the participants in 93.2%, while 6.8% were considered to have caused harm. In 72.7% of the theses the subjects were not informed of the research; in 73.6%, the researchers did not obtain permission from the subjects; and in 8.5% their privacy was not kept. An ethical score was assigned to each thesis, which varied between 0 and 15. The mean score was 5.02. PMID- 11221407 TI - Patient participation in decision making at the end of life as seen by a close relative. AB - The aim of the present study was to describe variations in patient participation in decisions about care planning during the final phase of life for a group of gravely ill patients, and how the different actors' manner of acting promotes or impedes patient participation. Thirty-seven qualitative research interviews were conducted with relatives of the patients. The patients' participation in the decisions could be categorized into four variations: self-determination, co determination, delegation and nonparticipation. The manner in which patients, relatives and caregivers acted differed in the respective variations; this seemed either to promote or to impede the patients' opportunities of participating in the decision making. The possibility for participation seems to be context dependent and affected by many factors such as the dying patient's personality, the social network, the availability of different forms of care, cultural values, and the extent to which nurses and other caregivers of the different forms of care can and want to support the wishes of the patients and relatives in the decision-making process. PMID- 11221408 TI - Users' views on palliative care services: ethical implications. AB - This article is based on the findings of a study that elicited the views of terminally ill patients (n = 15), their carers (n = 10) and bereaved carers (n = 19) on the palliative care services they received. It explores the range of ethical issues revealed by the data. Although the focus of the original study was on community services, the participants frequently commented on all aspects of their experience. They described some of its positive and negative aspects. Of concern was the reported lack of sensitivity to the role of the family among health professionals. The family, as carers, service users and advocates, represent a challenge to professional boundaries and the ethical norms of confidentiality and best interest. The accounts reveal the complexity of the ethical issues that characterize terminal care, issuing specific ethical challenges to nurses and other health professionals involved in this field. PMID- 11221410 TI - Comprehensive STD/HIV prevention education targeting US adolescents: review of an ethical dilemma and proposed ethical framework. AB - Adolescents are increasingly at risk for sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV) infection. The prolonged latency period, sometimes in excess of five years, and the incubation period of up to 10 years before the manifestation of symptoms, may foster adolescents' false sense of invincibility and denial as they often do not see the devastating effects of the disease in their peers until they are older. In turn, their practice of safer sex may be hindered and thereby contribute to the escalation of this public health crisis among sexually active adolescents. Prevention-focused recommendations were made in the USA as a result of this crisis. Recommendations were made to: (1) include STD/HIV education in the curricula of grades kindergarten to 12; (2) increase to at least 75% the proportion of primary care and mental health professionals who provide age-appropriate STD/HIV prevention counselling to adolescents; and (3) expand HIV prevention services to include age appropriate HIV education curricula for students in grades 4-12 in 95% of schools. Yet, in the USA, the provision of school-based comprehensive STD/HIV education has been difficult to achieve owing to certain limitations and, in some instances, legal action. These limitations include: limited student access; restricted content; and the implementation of sporadic and/or brief educational programmes. Given these recommendations and the fact that adolescents are acquiring STDs and HIV infections at increasing rates, and despite the limitations and legal actions, do health care professionals not have an ethical obligation to provide adolescents with comprehensive STD/HIV prevention education? This ethical dilemma will be discussed using the ethical decision making principles of 'autonomy' and 'beneficence', and a decision-making model proposed by Thompson and Thompson, and by Chally and Loric. PMID- 11221409 TI - Development of an instrument to investigate parents' perceptions of research with newborn babies. AB - Neonatal intensive care nurses are often involved in research protocols as investigators, research assistants or staff nurses implementing the protocol and providing support and explanations to families. It is important, therefore, that nurses have information about parents' understanding of and attitudes towards the research process. The purpose of this study was to begin an exploration of parents' perceptions about research with newborn babies through the development and validation of a survey instrument. The questionnaire included: demographic questions; scaled items about research with newborn babies; scenarios describing research studies that varied in degree of risk and benefit to the newborn baby; questions about parents' willingness to enrol their newborn baby in the studies described; and questions regarding circumstances under which consent should be sought. Content and face validity were established by an expert panel and a pilot test conducted with a small group of health care professionals and lay persons. A convenience sample of 231 parents of newborn babies completed the final version of the questionnaire. Factor analysis revealed seven factors corresponding to issues identified in the literature, providing evidence of construct validity. Parents appeared to have no difficulty in completing the instrument and all questions were answered by the majority of participants. It was concluded that the questionnaire had adequate psychometric properties and that a mixed method approach can be fruitful in exploring sensitive issues. PMID- 11221411 TI - Ethical dimensions of supervision: the supervisors' experiences. AB - Group-orientated supervision is provided continually to student nurses during their education. In the supervision process it is necessary to create a relationship between the supervisor and the supervisee that is based on an ethical, trusting relationship. The aim of the study was to investigate supervisors' (n = 18) experiences of the ethical dimensions of ongoing group orientated supervision. An additional aim was to describe the supervisors' values by which they are guided in supervision. Data were collected by means of an open ended questionnaire and analysed using the hermeneutic transformative process. The findings revealed the following themes: respect and responsibility; carefulness and sensitivity; reflection and confirmation; and genuineness and fairness. The values guiding the supervisors were dignity, normative ethics, privacy and confidentiality. PMID- 11221412 TI - Nurses' ethical conflicts: what is really known about them? AB - The purpose of this article is to report what can be learned about nurses' ethical conflicts by the systematic analysis of methodologically similar studies. Five studies were identified and analysed for: (1) the character of ethical conflicts experienced; (2) similarities and differences in how the conflicts were experienced and how they were resolved; and (3) ethical conflict themes underlying four specialty areas of nursing practice (diabetes education, paediatric nurse practitioner, rehabilitation and nephrology). The predominant character of the ethical conflicts was disagreement with the quality of medical care given to patients. A significant number of ethical conflicts were experienced as 'moral distress', the resolution of which was variable, depending on the specialty area of practice. Ethical conflict themes underlying the specialty areas included: differences in the definition of adequacy of care among professionals, the institution and society; differences in the philosophical orientations of nurses, physicians and other health professionals involved in patient care; a lack of respect for the knowledge and expertise of nurses in specialty practice; and difficulty in carrying out the nurse's advocacy role for patients. PMID- 11221414 TI - [Containers of perfusion fluid: plastic bottles]. PMID- 11221415 TI - [ONCO-RESE 19, a coordinated oncologic network]. PMID- 11221416 TI - [Superficial scars and hydrocolloids]. PMID- 11221417 TI - [Hungary, nurses fighting for their salary]. PMID- 11221419 TI - [Hygiene and nosocomial infections]. PMID- 11221418 TI - [Education of the diabetic patient: hypoglycemia and weight gain]. PMID- 11221420 TI - [To be a nurse-hygienist]. PMID- 11221421 TI - [Nosocomial infections and the nurse's responsibility]. PMID- 11221422 TI - [Taking blood samples: wearing gloves to prevent accidental exposure to blood]. PMID- 11221423 TI - [A practical course of implementing isolation of patients with infectious diseases]. PMID- 11221424 TI - [Isolation of patients with infection caused by multi-resistant bacteria]. PMID- 11221425 TI - [Handwashing--at the dawn of the third millenium]. PMID- 11221426 TI - Learning an invented inflectional morpheme in Spanish by children with typical language skills and with specific language impairment (SLI). AB - Cross-linguistic research on SLI has suggested that how the disorder is manifested depends on the ambient language. For example, research on Italian indicates that SLI children do not present difficulties with verb inflection, when compared with MLU-matched peers. This pattern contrasts with what has been reported for English-speaking children. The present investigation sought to examine SLI children's use of inflectional morphology through a language teaching task similar to that used by Connell (1987) and Connell and Stone (1992). To address cross-linguistic differences, children were speakers of a language similar to Italian in its verb agreement paradigm. Sixteen Puerto Rican Spanish speaking with SLI and 16 age-matched controls were taught a subject-verb agreement suffix that established the subject's gender. Half the children in each group were taught the new form via imitation. The rest of the participants were trained via a modeling procedure. Both comprehension and production of the target form were assessed. Results indicated significant differences across the SLI and typical groups for both comprehension and production of the inflectional morpheme, regardless of instructional strategy. These findings contradict what has been observed in previous studies on teaching an invented rule to children with SLI. They also suggest that inflectional morphology may be problematic even for children who are learning a morphologically rich language. The explanatory power of the process account and the linguistic account of SLI are explored as these pertain to the present findings, and suggestions for further research are discussed. PMID- 11221427 TI - Views of young people using augmentative and alternative communication systems. AB - Children with physical impairments who cannot use intelligible speech are often recommended augmentative and alternative communication (AAC) systems. In England and Wales, it is usually the job of speech and language therapists to support development in AAC skills. This paper reports findings from discussion with children and young people who use AAC systems concerning their attitudes and opinions towards the organization of speech and language therapy, the role of the speech and language therapist in school and issues concerned with AAC systems themselves. Six young adults and 17 children from London education authorities were interviewed on a one-to-one basis and in focus groups. Children were interviewed who had a communication aid incorporating at least 20 symbols and/or pictures and/or written words, language understanding at the two-word level and above, i.e. they demonstrated understanding of adult requests with at least two information carrying words. For children using communication aids, it is conceivable that their communication systems do not contain appropriate symbol vocabulary to express complex ideas, opinions and feelings. Consequently, a symbol-based interview tool was designed to allow children to express complex issues through visual means. Most children interviewed reported that their AAC system was useful to them. Further analysis of opinions revealed that negative attitudes towards AAC systems were primarily associated with operational issues (technical skills required to operate an AAC system) and issues of self image/identity, and to some degree, with a lack of perceived benefit in interaction. In apparent contrast to therapists' preferred models of working, children and young people identified a preference for therapy organized on a one to-one basis targeting linguistic and operational skills. It is suggested that more acceptable and individualized design of AAC systems could have implications for their use in school and other contexts. The value of service users' views in service planning and evaluation are discussed. PMID- 11221428 TI - A review of Clinical Terms Version 3 (Read Codes) for speech and language record keeping. AB - There may be bugs, there may be viruses, but computers are here to stay. Access to computers may vary greatly from 'seen one once' to daily usage. However, with an increasing dependence on electronic records, even the most remote therapist will ultimately be faced with computerization. To make this process as painless as possible some commonality in approach is logical. A common vocabulary, for instance, would ensure that dysphasia in Cape Town is the same as dysphasia in Dundee. This is great in theory but is Clinical Terms Version 3 (Read Codes) (CTV3) sufficient to encode records in clinical practice? It is to this end that the Speech and Language Therapy Department at Burton Hospital took part in a multidisciplinary project with the NHS Centre for Coding and Classification (NHS CCC). (NHS CCC became the NHS Information Authority, Coding and Classification on 1 April 1999.) Their CTV3 offers a standardized clinical terminology. An audit of patient case-notes found that 78% of the terms used by therapists were available in CTV3. Although there are many issues raised concerning electronic patient records, CTV3 presented as a potential vocabulary for recording patient information in this acute setting. PMID- 11221429 TI - Re: Evaluation of voice quality. PMID- 11221430 TI - Re: WILSTAAR. PMID- 11221431 TI - Re: Treatment of hypernasality. PMID- 11221432 TI - A preliminary account of phonological and morphophonological perception in young children with and without otitis media. AB - This investigation examined the effects of otitis media with effusion (OME) and its associated fluctuating conductive hearing loss on the perception of phonological and morphophonological /s/ and /z/ in young children. We predicted that children free of OME (OME-) would perform better than children with histories of OME (OME+). We also predicted that for the OME+ group morphological perception would be harder than phonological perception, because the former category carries an additional linguistic load (i.e., plurality). Sixteen children, ages 26 to 28 months (M = 26.5, SD = 0.6) were divided into two groups, the OME- (n = 8) and OME+ (n = 8) based on OME history during the first year of life. Subjects in the OME- group were free of the disease for 4/5 visits and pure tone average (PTA) was 12.6 dB HL (SD = 4.8). Subjects in the OME+ group had the disease on 3/5 visits and PTA was 23 dB HL (SD = 2.7). Experimental stimuli were six monosyllabic novel word-pairs. Members of each word-pair differed only in the presence of final voiced or voiceless fricative, marking the targets phonologically (e.g., [g [symbol: see text]]/[g [symbol: see text] s] as in 'law', 'loss') or morphophonologically (e.g., [daep]/[daeps] as in 'map' 'maps'). Subjects were taught the unfamiliar word pairs using a fast mapping procedure. Perception was tested with the bimodal preferential looking paradigm. Children in the OME- group performed significantly better than their OME+ counterparts. Individual word-pair analyses showed that OME+ group performed more poorly than the OME- group on one phonological and on two morphological targets, all ending with [s]. For the OME+ group, targets with final [s] posed greater difficulty than those with final [z], especially on morphophonological plural-(s) targets. The results suggested that the fluctuating hearing loss associated with OME might have a negative impact on speech perception. PMID- 11221433 TI - Prevalence and developmental course of 'secret language'. AB - The prevalence and developmental course of supposed 'secret language' was examined in a cohort of twins and closely spaced singletons pairs, with systematic assessments at 20 months and again at 36 months. Two forms of apparent 'secret language' were examined: (1) shared understanding--speech directed generally but unintelligible to the parent, although apparently clearly understood within the child pair, and (2) private language directed exclusively to the other twin/sibling--not intelligible to the parent, but apparently clearly understood and used only within the child pair. Both occurred in singleton pairs, but the rate was much higher in twins. In most cases it seemed to be a developmental phenomenon occurring in the second year of life with the emergence of immature speech, and decreasing considerably over the next 16 months. A small group of children, primarily male twins, was reported to use a private language at 36 months. This group had poorer cognitive and language functioning, and was characterized by highly dependent relationships. Some aspects of the twins' home environment were less stimulating and less responsive, most probably reflecting the abilities and relationships of the children. A follow-up of these children when they were approximately 6 years of age showed that language outcome was poor for the subgroup (n = 4) who did not develop normal language alongside the use of a private language. PMID- 11221434 TI - Nature of phonological delay in children with specific language impairment. AB - This study investigated the nature of phonological delay in a group of children with specific language impairment. It was asked whether phonological errors in this group of children were generated by a slow but normal language learning process or whether they reflected a selective impairment in some representations that enhance normal acquisition and use of a language phonology. A group of 10 children with SLI (mean age = 5.1) was compared with three groups of normal children who were matched in age (age control group, mean age = 5.1), in sentence comprehension and recalling (grammar control group, mean age = 3.7), or who exhibited a phonological performance lower than the age average (group with low phonological performance, mean age = 4.4). The four groups of children were assessed in terms of: (1) responses to a mispronunciation detection task; and (2) error profiles with complex and simple syllabic structures. Performance on the mispronunciation detection task showed that the group with SLI could distinguish a target lexical item from acoustic non-word stimuli that were highly similar to it in terms of phonetic characteristics. An analysis of overall error rate at this task showed, however, that four children with SLI had a much lower performance than normal children of the same age, even when the auditory stimuli were tokens of the target word, or non-words that were phonetically different from the target. A difficulty in coordinating vocal actions in an articulatory plan accounted for error profiles with simple syllabic structures both for some children with SLI and normal children with phonological performance lower than the age average. A severe difficulty with representing complex syllabic structures was a homogeneous characteristic of the group with SLI and worked as the main indicator of impaired, rather than simply slow, phonological development. PMID- 11221435 TI - Direct and indirect therapy for word sound deafness. AB - This paper evaluates two therapy programmes conducted with PK, an aphasic individual with word sound deafness. The first aimed directly to improve discrimination skills, using minimal pair tasks supported with lip reading. Disappointingly, there were no changes on discrimination tests after this therapy, even when PK could benefit from lip reading information. The second, indirect, programme of therapy aimed to change the communication behaviours of PK's wife. Strategies such as writing and simplifying information were modelled and practiced. A detailed information booklet, outlining the target strategies and explaining PK's main strengths and weaknesses supported the programme. Evaluation of this therapy involved pre- and post-therapy analysis of interactions between PK and his wife, with biographical questions forming the basis of the interactions. There were several changes after therapy on this measure. The number and length of communication breakdowns were reduced, and more questions were answered accurately. This study suggests that, in some cases of severe word sound deafness, indirect therapies may be most effective. PMID- 11221436 TI - Current concepts in the treatment of prostate cancer. PMID- 11221437 TI - MSNJ acts to improve services. PMID- 11221438 TI - A new strategy for MSNJ. Results of an organizational development study. PMID- 11221440 TI - Using CPT frequency reports to analyze E&M use. AB - Evaluation and management utilization is a significant compliance concern in the current health care environment. Understanding utilization patterns will assist the physician in determining whether significant differences exist between the physician's billed services and group or national norms. PMID- 11221439 TI - State-of-the-art prostate cancer treatment and research. A report from the Cancer Institute of New Jersey. AB - Prostate cancer is a devastating disease that will be diagnosed in approximately 200,000 men in 2001. New methods for screening, prevention, and treatment are being developed. In addition, novel agents for the treatment of resistant prostate cancer are being developed in clinical trials. This review summarizes the recent efforts in diet, screening, novel systemic therapies, and alternative medicine for prostate cancer. PMID- 11221441 TI - Disease and injury reporting requirements for NJ physicians. PMID- 11221442 TI - MSNJ launches enhanced HMO complaint system. PMID- 11221444 TI - Above all, do no harm. The national imperative: improve health care quality and reduce medical errors. PMID- 11221443 TI - Harrison S. Martland, MD. The Radium watch-dial workers and the evolution of industrial medicine. PMID- 11221445 TI - [Use of electrosurgery in patients with pacemaker and implanted defibrillator]. PMID- 11221446 TI - [The value of exercise test in acute coronary syndrome]. AB - In general, exercise testing in acute coronary syndrome (ACS) has been used in the assessment of physical capacity and to obtain prognostic information. Within recent years, however, a number of randomized studies have addressed the role of exercise testing in identifying patients, who may benefit from an invasive versus a conservative treatment strategy. According to the literature, a normal exercise test result after ACS is associated with an excellent clinical outcome. Patients who for clinical reasons are unable to perform an exercise test comprise a high risk group for future cardiac events. An invasive strategy is warranted in patients who continue to have angina and exhibit significant ST-segment depression in the exercise-ecg or reversible defects on perfusion scintigraphy. Based on the results of a recent, large scale randomized study, patients with unstable angina or acute non-Q-wave infarction appear to benefit from an early invasive treatment strategy--regardless of the results of a preceding exercise test. PMID- 11221447 TI - [Three-dimensional ultrasonography in obstetrics and gynecology]. AB - Medical ultrasound has during the last decades experienced enormous technological progress, and in obstetrics and gynaecology it has become an integral part of the clinical work. Within the last years several new ultrasound techniques have appeared. Three-dimensional ultrasound scanning (3DUS), in which there has been great interest, is one of them. Especially within obstetrics and gynaecology several papers on that topic describe promising results. Foetal diagnostics relying on morphological signs and accurate distance and volume measurements is one of the areas, believed to benefit from 3DUS. However, until now only few prospective works have been published, most of them counted as preliminary. One of the main reasons might be the huge technological challenge. It is proposed that technological progress over the next few years will allow feasible real-time 3D scanning. Thereby obstetrical and gynaecological ultrasound scanning will undoubtedly take another giant leap forward. PMID- 11221448 TI - [Mortality after administration of human albumin to critically ill patients with hypovolemia. An analysis of a systematic Cochrane review]. AB - A systematic Cochrane review strongly suggested that the administration of human albumin to critically ill patients with hypovolaemia increases mortality. This review has been widely criticised and the aim of the present paper was to analyse the original studies with regard to 1) the randomisation procedure, 2) the blinding procedure, 3) the indication of treatment, 4) whether treatment was clearly defined and consistent, 5) how normovolaemia was defined, and 6) the length of the follow-up period. None of the twelve studies analysed fulfilled common criteria in relation to evidence-based medicine. Consequently, there is no scientific evidence to support the conclusion that human albumin administered to critically ill patients with hypovolaemia increases the mortality. Thus, the validity and quality control of systematic Cochrane reviews may be questioned. PMID- 11221449 TI - [Sexual activity in ischemic heart disease. Risk and therapeutic possibilities]. AB - A major concern of patients with ischaemic heart disease is whether sexual activity is safe. In addition, patients are often reluctant to discuss sexual problems, including erectile dysfunction. Fear of sexual failure or fear of an acute ischaemic cardiac event as a result of sexual activity may create anxiety and lead to avoidance of sexual activity, which can significantly affect quality of life. In patients with a recent acute myocardial infarction the participation in a cardiac rehabilitation program should be strongly encouraged. The results are an improvement in physical capacity and self confidence. The performance of an exercise test at the time of hospital discharge following acute myocardial infarction is mandatory, and can be used in both risk stratification and cardiac rehabilitation. Patients who can manage a work capacity of at least 100 Watt without evidence of myocardial ischaemia or arrhythmias may without concerns take part in an active sexual life. Comprehensive information and appropriate use of pharmacologic agents for erectile dysfunction can add significantly to quality of life. PMID- 11221450 TI - [Surgical strategy in treatment of renal tumor complicated by tumor thrombosis in inferior vena cava]. AB - INTRODUCTION: In Denmark 650 renal cell carcinoma cases are diagnosed every year, and in 5-9% of the cases there is spread of the tumour in the form of tumour thrombosis in the inferior vena cava inferior. AIM: The purpose of this work is to describe the methods and outcome of operation regarding patients with such tumour thrombosis. According to the literature, the survival of these patients is not reduced provided there are no metastases to regional glands nor any distant metastases. METHODS: We describe 13 cases operated in the urological ward at Rigshospitalet (the Danish national hospital) during a nine-year period. RESULTS: In all 13 cases radical nephrectomy was performed and the tumour thrombus removed. In three cases the thrombus stretched into the right atrium, and the operations on these patients were performed in extra-corporal circulation. In one case the operation was performed in veno-venous bypass. There were two peri operative deaths; one patient died during the operation from uncontrollable bleeding, the other on the ninth postoperative day. In both cases the thrombus stretched into the atrium. There were minor complications in three out of the remaining 11 cases, and in the last eight cases there were no complications. The two year survival was estimated at 50%. CONCLUSION: On the basis the literature and our own results we recommend that patients with kidney tumour and tumour thrombus in the inferior vena cava are evaluated with a view to operation. PMID- 11221451 TI - [Use of outcome measures in physical medicine/rheumatological rehabilitation. Results of a questionnaire study]. AB - BACKGROUND: As part of the EU-project ProESOR (Project for the European Standardisation of Outcome Measurement in Rehabilitation), a survey was undertaken to investigate the use of Outcome Measures (OM) within rehabilitation across Europe. This paper presents some of the Danish results of this survey. AIM: Evaluate the extent of use of OMs in rehabilitation. MATERIAL: All 37 Rheumatology/Physical Medicine and Rehabilitation departments and institutions in Denmark. METHOD: A questionnaire was mailed to the institutions. This included questions about the institution and its personnel, and nine diagnostic groups: Low back pain, multiple sclerosis, neuromuscular disorders, rheumatoid arthritis, spinal cord lesions, stroke, traumatic brain injury, hip and knee replacement, and lower limb amputees, with estimation of the number of patients treated and the extent of use of OMs. RESULTS: The majority of the departments treated more than 200 in- and out-patients per year. Patients with low back pain and rheumatoid arthritis were the largest patient groups, followed by patients with hip and knee replacement and stroke. OMs were most frequently used with rheumatoid arthritis and, to a lesser extent, patients with low back pain. Although many departments used one or more OM, several did not use any at all. For each diagnostic group more OMs were used if the patient was treated in a department specialised for patients with the particular diagnosis. More OMs were used with patients who tended to have longer inpatient stays. CONCLUSION: There is little consensus regarding which OMs should be used. We recommend that this challenge be taken up. PMID- 11221452 TI - [Ultrasonic dissection in laparoscopic cholecystectomy. A safe alternative to patients with pacemaker]. AB - Use of electrocautery for laparoscopic surgery in patients with implanted pacemakers can create serious pace dysfunction. In these patients, the innovation of ultrasonic coagulation shears has provided the potential for safe routine laparoscopic cholecystectomy. We present a case where laparoscopic cholecystectomy was performed with the ultrasonic dissecting hook. The operation was converted to laparotomy due to unclear anatomy with further dissection using the ultrasonic hook. The intra- and postoperative courses were uneventful with no cardiac arrhythmias. More attention should be drawn towards this new surgical device so that patients with pacemakers may undergo routine laparoscopic surgery. PMID- 11221453 TI - [Three-dimensional ultrasonography of monoamniotic twins]. AB - A case of monoamniotic twins is described. Three-dimensional ultrasound scanning (3DUS) was used to visualise the fetuses lying in a single amniotic cavity. Entanglement of the umbilical cords with several knots was also visualised. The infants were delivered by elective caesarean section at 32 + 2 weeks with an uncomplicated postpartum course. Several knots found between the two umbilical cords, with separate placental insertion, were consistent with the ultrasound scan. We suggest that dedicated software solutions for volumetric ultrasound and knot analysis could contribute to a more precise description of the entanglement, which again would be a useful prognostic tool in the antenatal management and delivery of monoamniotic twins. PMID- 11221454 TI - [Picture of the month: subcutaneous emphysema]. PMID- 11221455 TI - [Ear implantations]. PMID- 11221456 TI - [Leukemia examination of personnel who were stationed in the Balkans. A statement from the Forsvarets Sundhedstjeneste]. PMID- 11221457 TI - [Use of depleted uranium and the risks in war]. PMID- 11221458 TI - [Reform of the borderline concept--a paradigmatic shift?]. PMID- 11221459 TI - [Ritual circumcision--a medico-social problem]. PMID- 11221460 TI - [The rubric "Picture of the month"]. PMID- 11221461 TI - [Circumcision]. PMID- 11221462 TI - [Ritual circumcision]. PMID- 11221463 TI - [Circumcision]. PMID- 11221464 TI - [Health screening--of "value" for the individual?]. PMID- 11221465 TI - [Chemokines and chemokine receptors. Review article]. AB - Chemokines form a new superfamily of small glycoproteins. They are key molecules that activate and direct the migration of different types of leukocytes from the blood stream into sites of infection and inflammation. In addition to this role certain chemokines have been reported to act on different types of cells (e.g. hematopoietic progenitor cells, dendritic cells, fibroblasts, keratinocytes). Other of them also play a role in wound healing, in angiogenesis and in viral infections. These molecules have a high degree of amino acid sequence homology and they have four conserved cysteins forming two essential disulphide bonds. They are divided into four classes (families) depending on the position of the first two cystein residues. Chemokines mediate their proinflammatory effects by binding to a variety of specific receptors, belonging to the G protein-coupled superfamily of seven-transmembrane (serpentine) receptors. Some of this receptors serve as coreceptors for HIV-viruses, some of them could be expressed as markers preferentially in Th1 or Th2 subpopulations. This paper summarizes data on chemokines and their receptors, target cells and production in physiological and pathological conditions. PMID- 11221466 TI - EEG spectrum as information carrier. AB - Spontaneous and provoked changes of vigilance and consciousness are determined by TCS (thalamocortical system) activity. This is relatively easy to monitor using EEG, which is a complex curve but open to analysis, e.g., by means of FFT (fast Fourier transformation). Twenty six persons (six normal controls, twelve epileptics, eight dements) had EEG recorded during rest, reaction to sound, and perception to simple tones or chords from Smetana's symphonic poem Vysehrad. The length of reaction time was found dependent on FFT changes: the longer the time, the higher are the delta and the lower the alpha activities in the EEG spectrum. However, with alpha increasing during relaxation, the reaction time grew longer regardless of whether delta had increased due to hyperventilation, sleep or subclinical epileptic discharges. During the perception of tones, FFT showed changes in the alpha and delta bands different from those during the perception of chords, and different again during relaxation, and that in both normal controls and epileptics. The demented persons revealed no discernible FFT differences in the perception of either tones or chords, the only differences were found in the resting sections of the spectrum. One and the same stimulus produced a stereotype FFT response, i.e., different stimuli elicited different FFT response in healthy and epileptic persons. The dements responded to identical stimuli differently, and had stereotype FFT response elicited by the same stimuli. The results suggest that FFT can represent the information content of the EEG curve and, indirectly, also that of micro-EEG as it reverberates between the thalamus and the cortex in the form of neuronal activity impulsations. This interneuronal impulsation coding is disordered in dements with atrophy of the cortex; it is marked, on the one hand, by increased variability in the perception of identical stimuli, and, on the other hand, by impaired differentiation, and, consequently, by increasingly stereotype responses to different stimuli. PMID- 11221467 TI - The evaluation of thyroid and islet autoantibodies in type 1 diabetes mellitus. AB - Type 1 diabetes mellitus is an autoimmune disease in which the presence of different autoantigens can often be found. The aim of our study was to evaluate the prevalence of antibodies against insulin (IA) and autoantibodies against glutamic acid decarboxylase (anti-GAD), tyrosine phosphatase IA-2 (anti-IA-2), thyroid microsomal peroxidase (anti-TPO) and thyroglobulin (anti-TG) in 55 randomly selected Type 1 diabetic patients (34 males, 21 females). Mean age of these patients was 39 +/- 12 yrs, mean duration of diabetes 18 +/- 13 yrs. Positivity of anti-GAD was found in 29 (58%) patients, anti-IA-2 in 13 (25%) patients, IA in 46 (85%) patients, anti-TPO in 10 (21%) and anti-TG in 11 (23%) patients. Simultaneous positivity of thyroid and islet autoantibodies was found in 6 (11%) patients whereas the positivity at least one of them was in 38 (69%) patients. No relationship between glycated hemoglobin and autoantibody concentration was found in the whole group of patients. The autoimmune thyroid disease was newly detected in 4 patients from high concentration of thyroid autoantibodies together with impaired TSH and T4 values and ultrasonography finding. No clinical evidence of thyroid disease was previously found in these patients. Positivity of anti-GAD or anti-IA-2 was found in almost 65% and of any thyroid autoantibody in almost 30% of our patients. Four patients with autoimmune thyroid disease were newly identified. We conclude that the evaluation of thyroid autoantibodies in Type 1 diabetic patients may improve the diagnosis of thyroid disease in very early stage and thus prevent consequent complications. PMID- 11221468 TI - The influence of methylene blue and L-NAME on the development of streptozotocin induced diabetes in rats. AB - The cytokine-induced overproduction of nitric oxide by immunocompetent cells with subsequent development of oxidative stress is suggested to be one of important pathophysiological mechanisms of the pancreatic beta cells damage in streptozotocin-induced experimental diabetes. The aim of our study was to compare the influence of two nitric oxide inhibiting compounds: methylene blue and L-NAME (N-omega-nitro-L-arginine-methyl ester) on the streptozotocin diabetes development and the oxidative stress parameters in male rats. Blood glucose, glycated haemoglobin, serum malondialdehyde concentration and erythrocyte superoxide dismutase activity were measured in control, diabetic (streptozotocin 70 mg/kg i.p.), methylene blue (50 mg/kg in the food), and diabetic group treated simultaneously with methylene blue (10 animals in each group). In the second experiment the L-NAME was used instead of methylene blue. It was found that both methylene blue and L-NAME partially suppressed the development of diabetes, but did not unambiguously influence the oxidative stress parameters. We conclude, that both methylene blue and L-NAME partially suppress the development of streptozotocin-induced diabetes in rats. The precise mechanism of this effect is not clear. We failed to demonstrate clear effect of methylene blue and/or L-NAME on oxidative stress development in diabetic rats. PMID- 11221469 TI - Effect of exogenous estrogen on male rats bone. AB - Not only androgens however but also estrogens may be important for the growth and maintenance of the male skeleton. The estradiol treatment of intact male rats significantly decreased serum testosterone concentrations and the weight of seminal vesicles, however, not to the level of castrated animals. In spite of a low serum testosterone the administration of estradiol did not produce changes in the density, ash weight and mineral content of the tibia. In castrated rats with low serum testosterone bone density, ash weight and mineral content of the tibia were decreased, compared with intact controls. These our observation indicate that estrogen has a important role to retain bone mass in males as well as females. PMID- 11221470 TI - [Effect of growth hormone and other hormones on trabecular bone structure in acromegaly]. AB - The influence of growth hormone upon trabecular bone remodelation is not definitely clear. The authors of this study compared static and dynamic histomorphometric data of bone patterns of 28 numbered group of acromegalics and 35 numbered group of healthy individuals. They correlated also levels of growth hormone, thyroxine, prolactin and testosterone in men with histomorphometric parameters in acromegalic patients. The results showed statistically significant differences between normal and acromegalic trabecular bone, which has comparable trabecular volume, but significantly wider bone trabeculae and lower mean trabecular density. There were no correlations found between growth hormone levels and levels of thyroxine, prolactin, measured testosterone and histomorphometric parameters. PMID- 11221471 TI - [Duration of the effect of growth hormone on spongious bone]. AB - The influence of duration of growth hormone action (length of history of acromegaly) upon acromegalic trabecular bone histology was followed in 28 biopted active acromegalics. The histology of trabecular bone was standardized by histomorphometric parameters. No statistically significant relation between length of acromegalic history and any of measured histomorphometric parameters (trabecular volume, trabecular thickness, absolute osteoid volume and osteoid surface) was found. The reason of this finding is probably consequence of serum growth hormone level, which changes during period of history in each acromegalic patient. With aim to find out if growth hormone influences bone histomorphometry of acromegalics after causal treatment (removal of hypophyseal adenoma causing overproduction of growth hormone), the comparison of histomorphometry from bone bioptic patterns of six active acromegalics with their bone patterns average 9.3 years after hypophyseal operation was done. With the exception of one eugonadal woman, all acromegalics were hypogonadal in time of second biopsy. Nevertheless no statistically significant differences between histomorphometric data (trabecular volume, trabecular thickness, surface and absolute volume of osteoid) were found. With knowledge of fact that there is low number of rebiopted acromegalics, these results could support idea of protective action of growth hormone upon trabecular bone of acromegalics during nine years after treatment. PMID- 11221472 TI - [Electronic medical journals are a reality of today]. AB - Internet is changing the way that science is communicated. The future of medical publishing is going electronic. Publishing medical electronic journals is becoming a standard routine for all prominent publishers. Present-day trends in the publishing of medical electronic journals are outlined. PMID- 11221473 TI - [Medical schools and science]. PMID- 11221474 TI - [Perspectives in gene therapy of polycystic kidney disease]. AB - An overview concerning principles and development of gene therapy from experimental models to first trials of application gene therapy in clinical medicine is provided. Increased attention is focused on specific methods of gene transfer into kidneys. Renal hereditary diseases represent an important subgroup of the diseases of the kidney, leading non rarely to chronic renal failure; (autosomal dominant) polycystic kidney disease remains to be one of the most frequent and clinically important. Preliminary conditions, including technical tools and pathophysiological insights to be fulfilled, as prerequisites for an application of gene therapy in polycystic kidney disease, are discussed. PMID- 11221475 TI - [Pathophysiology of development of acute pancreatitis]. AB - Acute pancreatitis is a severe illness with unclear prognosis and mortality rate ranging from 5 to 70%. Dynamic observation of changes in systemic inflammatory response of the body may be helpful in estimating the development of acute pancreatitis as well as giving an idea of therapeutical possibilities. It is obvious, that the intensive therapeutic intervention may reduce the influence of secondary insults (ischemic-reperfusion syndrome, hypoxia, disrupted physiological function of the bowel) on pancreatic tissue. Surgery is limited only for precisely specified indications in the latter stage of acute pancreatitis (secondary inflammation of the necrosis). In this paper we conclude some pathophysiological mechanisms involved in the development of acute pancreatitis. PMID- 11221476 TI - Supracondylar fracture of the humerus in children--closed pinning. AB - The supracondylar fracture of the humerus is one of the most common in children, approximately one hundred per year, in Kuwait. The treatment consists in manipulation and fixation by plaster of Paris in the most stable position, usually maximal possible flexion in the elbow joint. For irreducible or unstable cases a percutaneous fixation by Kirschner wires was introduced in September 1993. Two or three Kirschner wires were used either parallel from radial condyle or cross fixation from ulnar and radial condyle. Cross fixation was used in older children without swelling of the elbow. This method has helped to reduce and stabilize the fracture allowing fixation of the elbow at 90 degrees flexion reducing the risk of the blood supply disturbance. The aim of this study was to find rules for proper selection of these two types of fixation. PMID- 11221477 TI - [Laparoscopic method of surgical treatment of inguinal hernia]. AB - Authors present the both method of laparoscopic inquinal hernia repair. They prefer laparoscopic praeperitoneal approach using prolene mesh 6 x 11 cm. PMID- 11221478 TI - [Antibiotic prophylaxis in hip joint surgery]. AB - Nosocomial deep wound infections are serious complications after hip joint surgery. Our aim was to determine whether there is a difference in rates of nosocomial infections between group of patients after elective surgery of hip replacement and group of patients with hip replacement after trauma. Both groups of patients had perioperative prophylaxis with amoxycillin. We found that the overall trauma patients infection rate was 0.9 per cent compared with 1.5 per cent for elective surgery infections. In both groups of patients a postsurgery stress was documented according to increase of acute phase proteins (C-reactive protein, orosomucoid and fibrinogen) in plasma for a minimum 10 days after surgery. We conclude, that both groups of patients had benefit from amoxycillin prophylaxis therapy. PMID- 11221479 TI - [Evaluation of the effect of plastic casts from the aspect of prevention of thromboembolic disease]. AB - Immobilization after trauma escalates risk of thrombosis. Our objective was to determine whether there is a difference in rates of deep vein thrombosis (DVT) after immobilization with plastic casts or routinely plaster of Paris in trauma patients. Despite both groups of patients do not show difference in blood coagulation tests (APTT, TT, PT, levels of fibrinogen and of D-dimer in plasma) during time of immobilization the evidence of DVT according to scintigraphy was lower in group of patients with plastic casts (3 per cent to 10 per cent). PMID- 11221480 TI - [Traumatic asphyxia with an unusual etiology. Case report]. AB - The authors present a casuistry of the injury endangering the life, which was caused by the unusual mechanism. The injured person was pulled inside of a conveyer and while shifting, not only his arm and physical (brachial) plexus was damaged, but he was also and especially, strangled by his clothes and he was seriously asphyxiated, which origin was in the first phase unexplainable. PMID- 11221481 TI - [EEG findings in patients with systemic lupus erythematosus]. AB - We have examined electroencephalography (EEG) and Mini-Mental State Examination (MMSE) in 38 patients with verified diagnosis of systemic lupus erythematosus (SLE). In the clinical neurological finding there were epileptic attacks in 9 patients, 10 patients suffered from stroke, 15 patients from lupus headache, 4 patients from psychosis, in 15 patients cranial neuropathy was present, in one person extrapyramidal syndrome. EEG findings were in 12 patients normal (32%), in 26 patients abnormal (66%). In 3 cases there were focal abnormalities (8%), in 19 cases episodic ones (48%), four times abnormalities were diffuse (10%). Diffuse abnormalities correlated in EEG findings with case history of GM attacks. PMID- 11221482 TI - [Anatomic illustration and its authors at the Medical School in Prague]. AB - This article is a longer version of the introductory address opening the exhibition of anatomical illustration in the Academic Club of First Medical Faculty of Charles University in May 1999. The history of anatomical illustration, its significance and its two main forms, scientific drawing and didactical illustration, are shortly introduced. The development of this form of art at the Medical Faculty in Prague is shown and is demonstrated by examples of illustrations. Two old authors of illustrations are mentioned: an unknown author of illustrations of the first illustrated textbook of anatomy in Prague that was written by Ch. S. a Zeidlern, and F. Belopotocky who illustrated the Atlas of Anatomy by W. Stanek written in Czech in 1840. In more detail are discussed the following artists and anatomical illustrators of 20th century connected with the Institute of Anatomy of Charles University: J. Rejsek, E. Illing, S. Machacek, M. Med, V. Seichert, I. Helekal a J. Kacvinsky. PMID- 11221483 TI - [What your personal archive should contain. Practical suggestions for the young (and not so young) researcher]. AB - In science it is indispensable to be able to organise knowledge. It is a prerequisite of efficient scientific research to have also a good system of filing and organisation for relevant documents. This means that the researcher must be able to identify and properly file--right from the start of his or her career--all documentation and records which will also be useful to future research. This paper contains a number of practical recommendations on how to establish and maintain the scientist's personal archive; how to classify and select documents; and how to archive them in a way which allows for easy retrieval. The aim of this paper is to eliminate all errors and omissions, as subsequent rectification can be laborious and time consuming. Documents are arranged beginning with those which are important for the researcher as an employee (representing his personal portfolio) and are followed by documents attesting to his scientific competence and experimental skills (presentations at conferences, published papers, teaching activities, grant projects, etc.). It is important and useful to conduct an occasional review of one's personal archive, to update and revise some documents, and to discard others. A change of employment or affiliation usually presents a good opportunity for such a review. An archive which is systematically maintained throughout a researcher's career is a valuable source of objective personal reminiscences and reviews of scientific development. PMID- 11221484 TI - [Arnold Jirasek and his Clinic in the fatal years of 1939 to 1959]. PMID- 11221485 TI - Change: chaos or challenge? PMID- 11221486 TI - Neuropsychopharmacology of pathological aggression and sexuality. PMID- 11221487 TI - The neurobiology, neuropharmacology, and pharmacological treatment of the paraphilias and compulsive sexual behaviour. AB - There has been increasing interest in the treatment of sexual disorders in recent years. Sexual disorders are classified in DSM-IV as sexual dysfunctions, paraphilias, and gender identity disorders. The sexual dysfunctions are nondeviant or nonparaphillic. The sexual dysfunction disorders should include "hyperactive sexual desire disorder" under sexual desire disorders. Further, there should be a specifier for paraphilias of "with hypersexuality" or "without hypersexuality." There is still incomplete understanding of the neurobiology of sexual disorders although functional neuroanatomy and neoropharmcological research has exposed the neurotransmitters, receptors, and hormones that are involved in sexual desire. Various pharmacological agents including serotonin reuptake inhibitors, antiandrogens, LHRH agonists, and others have been documented as reducing sexual desire. An algorithm for the use of these drugs in the treatment of the paraphilias as well nonparaphilic hypersexuality is outlined. The modes of action, dosages, aims of treatment, and usual methods of prescribing these agents is reviewed in this article. Some future directions of research in pharmacological treatment is also discussed. PMID- 11221488 TI - The neuropsychopharmacology of criminality and aggression. AB - Although the idea that aggression has biological components is not a new one, recent research in genetics, neuropsychopharmacology, and neuroimaging has helped clarify the biological contributions to aggression. Studies to date have focused on serotonergic function and impulsive aggression. Reduced levels of cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) are associated with impulsive aggression. Pharmacochallenge studies have found decreased serotonergic responsiveness associated with impulsive aggression. Neuroimaging studies suggest a role for the prefrontal cortex, along with other regions of the brain, in the expression of aggression. Serotonin is not the only aspect of brain function implicated in impulsive aggression, and further work is being done on other neurotransmitters and neuropeptides. PMID- 11221489 TI - A social problem index for Canada. AB - OBJECTIVE: To construct an index that represents the general level of social problems among Canadian provinces and territories. METHOD: Factor weights were used to combine provincial and territorial rates for homicide, attempted murder, assault, sexual assault, robbery, divorce, suicide, and alcoholism into a single Social Problem Index. RESULTS: The resulting index demonstrated strong positive intercorrelations among its factors across provinces. That is, provinces that showed high rates on one factor tended to show high rates on the others as well. The validity of the Social Problem Index is demonstrated by its positive correlation with an independent measure of the likelihood of having experienced personal trauma. CONCLUSIONS: The robust nature and apparent validity of the Social Problem Index suggest that it can be well used for needs assessments and theoretical studies and as a feedback mechanism to national, provincial, and community leaders on the social problem status of their particular jurisdictions. PMID- 11221490 TI - [Introduction to genetic psychiatry: progress in uncovering genetic susceptibility to psychiatric disorders]. AB - The recent progress in human genetics suggests major benefits in clinical practice, including psychiatry. This article introduces the research methodology used in psychiatric genetics and explains how it is applied, for a better understanding of the challenges facing psychiatric genetics and the strategies being used to overcome them. We will review the evidence of genetic factors in psychiatric disorder etiology as well as the specificity or non-specificity of their expression. We will discuss problems associated with the approximate nature of diagnostic methods, the incomplete penetrance and the genetic heterogeneity of psychiatric disorders, the presence of phenocopies and our uncertainty concerning the mode of inheritance of psychiatric disorders. Finally, we will provide an overview of the most promising results and set out priorities for future studies. PMID- 11221491 TI - Is schizophrenia on the decline in Canada? AB - OBJECTIVE: To examine changes in prevalence rates of treated schizophrenia over 10 years in a small urban teaching centre using data from the Kingston Psychiatric Record Linkage System (KPRLS). METHOD: The KPRLS, a psychiatric case register established in 1984, collects and links demographic, diagnostic, and service use information for all psychiatric inpatients, outpatients and emergency contacts at the 3 hospitals in Kingston, Ontario. A preliminary comparison of first admissions for schizophrenia used chart review (1976-1978) and KPRLS data (1996-1998). The KPRLS data were used to calculate population-based prevalence rates of treated schizophrenia in 3 census years (1986, 1991, 1996) for patients in the 2 counties closest to Kingston. RESULTS: The preliminary comparison showed a 42% decrease in the number of first-admission schizophrenia cases over 20 years. In the main study, the annual inpatient prevalence rates decreased significantly (52%) from 1986 to 1996 with no corresponding change in outpatient rates, regardless of sex. Although total major affective disorders increased, this was due to an increase in major depression, not bipolar disorder. CONCLUSIONS: This is the first Canadian case-register study to support the widely reported falling rates of schizophrenia in other parts of the world over the last 40 years. Since this is a geographically limited prevalence study based on only 10 years of data, further research over longer periods of time in other regions of the country is required to support or refute these findings. PMID- 11221492 TI - Serum lipid concentrations in patients with comorbid generalized anxiety disorder and major depressive disorder. AB - OBJECTIVE: To examine the lipid levels in a sample of patients with comorbid generalized anxiety disorder (GAD) and major depressive disorder (MDD). METHODS: Serum lipid concentrations were examined in 40 patients with both GAD and MDD, in 27 patients with MDD only, in 26 patients with GAD only, and in 24 healthy control subjects. RESULTS: All mean serum cholesterol concentrations are presented in Table 1. The mean serum total cholesterol concentration in patients with both GAD and MDD was significantly higher than in MDD-only patients, GAD only patients, and control subjects. The triglyceride concentration was also significantly higher in patients with both GAD and MDD than in MDD-only patients, GAD-only patients, and control subjects. Patients with both GAD and MDD had a lower mean high-density lipoprotein cholesterol (HDL-C) concentration than did patients with GAD only and control subjects. The serum concentration of low density lipoprotein cholesterol (LDL-C) was higher in patients with both GAD and MDD than in patients with MDD only and GAD only and healthy control subjects. CONCLUSIONS: Our findings indicate that the patients with both GAD and MDD have increased serum cholesterol, triglyceride, and LDL-C and reduced HDL-C levels. These patients may have a greater risk of mortality from coronary artery disease (CAD) than do patients with either depression or anxiety disorder. PMID- 11221493 TI - Regression toward the mean: its etiology, diagnosis, and treatment. AB - This paper explores the phenomenon of "regression toward the mean." The primary effect of this is to affect scores on retesting so that they are closer to the population mean. Thus, people who are selected for inclusion in a study because their scores on some measure are above (or below) some criterion have values on retesting that are less extreme. This may make it appear that the study participants have improved; this will occur even in the absence of an effective intervention. We explore the reasons for regression toward the mean and how it can be detected and discuss some methods that may minimize its effects. PMID- 11221494 TI - Adverse reactions to St John's Wort. AB - OBJECTIVE: To report 2 cases of adverse reactions to St John's wort, a popular herbal treatment for depression. METHOD: We present 2 case histories and review the existing literature regarding St John's wort. RESULTS: St John's wort may cause serotonin syndrome in sensitive patients. In addition, St John's wort may be associated with hair loss. CONCLUSIONS: For clinical reasons, it is important to recognize and report adverse reactions to herbal remedies and to document that these treatments have side effects commensurate with their potent action on brain neurochemistry. PMID- 11221495 TI - Is the minimum duration of hypomania in bipolar II disorder 4 days? PMID- 11221496 TI - Combination risperidone and quetiapine therapy in refractory schizophrenia. PMID- 11221497 TI - Supersensitivity psychosis in patients with schizophrenia after sudden olanzapine withdrawal. PMID- 11221498 TI - Galactorrhea induced by paroxetine. PMID- 11221499 TI - Obsessive-compulsive symptoms secondary to methylphenidate treatment. PMID- 11221500 TI - "Internet delusion" in a patient with a schizoaffective disorder. PMID- 11221501 TI - The postsurgical lumbosacral spine. Magnetic resonance imaging evaluation following intervertebral disk surgery, surgical decompression, intervertebral bony fusion, and spinal instrumentation. AB - It should be clear to those who perform and interpret medical images of the spine following one or more forms of surgical therapy that the images are often difficult to interpret in part because of the superimposition of the original disease process, alteration engendered by the surgery, or a complication of the surgical procedure. Although long-term experience in this area is helpful in regard to improving interpretive skills, certain sequela can be predicted regardless of the interpreter's background. Once the normal or expected postsurgical findings are understood, the subtle and gross changes that depart from these observations can be analyzed better. The importance of a high level of competence in the domain of post-therapeutic neurodiagnostic imaging is in the knowledge that the patient returning for restudy may be acutely in distress or even in medical danger (e.g., postoperative spondylitis). In fact, the clinical presentation posttherapeutically may well be more severe or dire than was observed pretherapeutically. An indepth appreciation of the broad range of clinicoradiologic possibilities as presented [figure: see text] here should place the medical imaging physician in an excellent position to provide an experienced diagnostic evaluation in the patient presenting with recurrent or new signs and symptoms following any one of the spectrum of possible spinal surgical procedures. PMID- 11221502 TI - Imaging of lumbar degenerative changes involving structures other than disk space. AB - Degenerative changes in the lumbar spine involve intervertebral disks and intervertebral posterior elements at different extents. Much less attention has been directed toward degenerative changes of the posterior vertebral elements, however, when compared with intervertebral disk degeneration. These changes may involve the apophyseal joints, the bony elements of the neural arch, the intervening soft tissues, and the spinal longitudinal ligament. Roentgenographic, CT, and MR findings in these changes are depicted. PMID- 11221503 TI - Imaging of spinal infection. AB - MR imaging is the modality of choice for the detection, staging, and differential diagnosis of inflammatory disorders of the spine. Infectious spondylitis is characterized by the involvement of two adjacent vertebrae and the intervening disk with severe BME and early destruction of the end plates. The disk space is narrowed and typically exhibits water-equivalent signal intensity on T2-weighted or STIR images. Prevertebral and epidural extensions, abscess formation, enhancement of the BME, the disk space, and the surrounding granulation tissue are well demonstrated by gadolinium-enhanced images. Cervical spondylitis frequently involves more than one level. Bone marrow abnormalities may be subtle at this level and increased signal intensity of the disk space on T2-weighted or STIR images is an important finding. The risk for neurologic complications is increased. Granulomatous infections caused by tuberculosis, brucellosis, fungi, and parasites, including hydatid disease (Echinococcus), are frequently associated with imaging findings different from those seen with nonspecific bacterial infection. In patients with chronic infectious spondylitis, diffuse reactive bone marrow changes with decreased signal intensity on T1-weighted images, increased signal intensity on T2-weighted and STIR images, and increased uptake after gadolinium administration may occur. This phenomenon is probably caused by reactive bone marrow stimulation, simulating diffuse hematologic neoplastic disease. Erosive intervertebral osteochondrosis with bandlike disk gadolinium enhancement and BME, which is commonly associated with local pain, is the most important differential diagnosis of bacterial spondylitis. PMID- 11221504 TI - Vertebral tumors and pseudotumors. AB - This article discusses lesions that may present as vertebral tumors at radiologic examination. Conditions are discussed in order of decreasing frequency: pseudotumoral lesions, vertebral metastases, bone marrow diseases, and primary vertebral tumors, which are relatively uncommon. The differential diagnosis between nontraumatic benign and malignant vertebral collapses is also discussed. PMID- 11221505 TI - Imaging lumbar spinal stenosis. AB - The entire concept of spinal stenosis is based on the assumption that there is a minimal space necessary for the function of the neural content of the spinal canal, and this space, under certain circumstances, gets too small. This may seem self evident, but it was not until the middle of the previous century that there was sufficient focus on this concept to establish the diagnosis of lumbar spine stenosis. PMID- 11221506 TI - Radiologic assessment of lumbar intervertebral instability and degenerative spondylolisthesis. AB - Despite many efforts, there is no clear and widely accepted definition of lumbar instability because there are no unquestionable and currently applicable clinical or radiologic criteria available for this entity. This article reviews the current concepts of lumbar instability and the different imaging modalities used to make the diagnosis as evident as possible. PMID- 11221508 TI - The histologic diagnosis of melanoma. AB - The pathologic diagnosis of melanoma is of crucial importance because it provides the patient and his or her attending physician with the knowledge of a potentially life-threatening or an almost curable condition. The histopathologic diagnosis of melanoma is based on the simultaneous or systematic assessment of several well-known histopathologic features. This article discusses the author's approach to the histopathologic diagnosis of melanoma for specific situations. PMID- 11221507 TI - Acquired degenerative changes of the intervertebral segments at and suprajacent to the lumbosacral junction. A radioanatomic analysis of the nondiskal structures of the spinal column and perispinal soft tissues. AB - In earlier evolutionary times, mammals were primarily quadrupeds. However, other bipeds have also been represented during the course of the Earth's several billion year history. In many cases, either the bipedal stance yielded a large tail and hypoplastic upper extremities (e.g., Tyrannosaurus rex and the kangaroo), or it culminated in hypoplasia of the tail and further development and specialization of the upper extremities (e.g., nonhuman primates and human beings). In the human species this relatively recently acquired posture resulted in a more or less pronounced lumbosacral kyphosis. In turn, certain compensatory anatomic features have since occurred. These include the normal characteristic posteriorly directed wedge-shape of the L5 vertebral body and the L5-S1 intervertebral disk; the L4 vertebral body and the L4-L5 disk may be similarly visibly affected. These compensatory mechanisms, however, have proved to be functionally inadequate over the long term of the human life span. Upright posture also leads to increased weight bearing in humans that progressively causes excess stresses at and suprajacent to the lumbosacral junction. These combined factors result in accelerated aging and degenerative changes and a predisposition to frank biomechanical failure of the subcomponents of the spinal column in these spinal segments. One other specific problem that occurs at the lumbosacral junction that predisposes toward premature degeneration is the singular relationship that exists between a normally mobile segment of spine (i.e., the lumbar spine) and a normally immobile one (i.e., the sacrum). It is well known that mobile spinal segments adjacent to congenitally or acquired fused segments have a predilection toward accelerated degenerative changes. The only segment of the spine in which this is invariably normally true is at the lumbosacral junction (i.e., the unfused lumbar spine adjoining the fused sacrum). Nevertheless, biomechanical failures of the human spine are not lethal traits; in most cases today, mankind reaches sexual maturity before spinal biomechanical failure precludes sexual reproduction. For this gene-preserving reason, degenerative spinal disorders will likely be a part of modern societies for the foreseeable eternity of the race. The detailed alterations accruing from the interrelated consequences of and phenomena contributing to acquired degenerative changes of the lumbosacral intervertebral segments as detailed in this discussion highlight the extraordinary problems that are associated with degenerative disease in this region of the spine. Further clinicoradiologic research in this area will progressively determine the clinical applications and clinical efficacy of the various traditional and newer methods of therapy in patients presenting with symptomatic acquired collapse of the intervertebral disks at and suprajacent to the lumbosacral junction and the interrelated degenerative alterations of the nondiskal structures of the spine. PMID- 11221509 TI - The genetics of cutaneous melanoma. AB - Although germline mutations in CDKN2A are present in approximately 25% of large multicase melanoma families, germline mutations are much rarer in the smaller melanoma families that make up most individuals reporting a family history of this disease. In addition, only three families worldwide have been reported with germline mutations in a gene other than CDKN2A (i.e., CDK4). Accordingly, current genomewide scans underway at the National Human Genome Research Institute hope to reveal linkage to one or more chromosomal regions, and ultimately lead to the identification of novel genes involved in melanoma predisposition. Both CDKN2A and PTEN have been identified as genes involved in sporadic melanoma development; however, mutations are more common in cell lines than uncultured tumors. A combination of cytogenetic, molecular, and functional studies suggests that additional genes involved in melanoma development are located to chromosomal regions 1p, 6q, 7p, 11q, and possibly also 9p and 10q. With the near completion of the human genome sequencing effort, combined with the advent of high throughput mutation analyses and new techniques including cDNA and tissue microarrays, the identification and characterization of additional genes involved in melanoma pathogenesis seem likely in the near future. PMID- 11221510 TI - Dysplastic melanocytic nevi and prognostically indeterminate nevomelanomatoid proliferations. AB - This article reviews the concept of dysplasia and the distinguishing features of dysplastic nevi, including their premalignant potential, their biologic markers of tumor progression, and their reproducibly recognizable clinical and histologic characteristics. An additional emphasis is placed on describing gray zone melanocytic neoplasms with hybrid histopathologic and biologic characteristics between nevi and melanoma. In particular, dysplastic nevi with high-grade and dermal dysplasia and other potentially related, prognostically indeterminate, nevomelanomatoid proliferations (PINM tumors), including the more recently recognized nevoid melanoma and minimal deviation neoplasms, are discussed. Because of their overlapping features with more overtly benign and malignant neoplasms, these lesions may confound precise determination of biologic outcome. Accordingly, the concept of prognostic indeterminacy and the use of the term PINM tumors to connote these problematic lesions are introduced. PMID- 11221511 TI - Thin melanomas. AB - Thin melanoma refers to that grouping of melanomas that statistically have a good prognosis and survival rate. A small but significant percentage of these lesions metastasize and cause mortality. Histologically, these lesions comprise a diverse grouping of tumors of any intraepidermal growth pattern; in the radial or vertical growth phase; or in anatomic level I, II, III, or IV. Additional histologic findings may also be variably present, such as regression, tumor infiltrating lymphocytes, and mitoses. Molecular studies suggest that thin melanomas may have different properties to thicker and metastatic melanomas. The factors governing the ability of thin melanomas to metastasize and cause mortality are not known. Certain histologic and molecular parameters, some of which have been alluded to previously, may provide clues to understanding the parameters governing the aggressive nature of some of these lesions. Further research is required to enhance our understanding of thin melanomas. PMID- 11221512 TI - Primary noncutaneous melanoma. AB - Primary noncutaneous melanomas are rare neoplasms that affect patients in an older age group than primary cutaneous melanomas. The prognosis is worse than primary cutaneous melanomas because of the advanced stage at the time of diagnosis, the rich vascular and lymphatic supply of mucosal sites, and the lack of clinical suspicion of the tumor because of its rarity. The initial treatment is surgical resection but the location may make it technically difficult to obtain complete tumor removal. Unlike cutaneous melanoma, sun exposure is not a risk factor for noncutaneous melanomas. Darker-skinned individuals may have a higher incidence of some noncutaneous melanomas, such as anorectal melanomas. It is important for clinicians and pathologists to recognize primary noncutaneous melanomas to provide early detection and optimum management. PMID- 11221513 TI - Minimal deviation melanoma. Borderline and intermediate melanocytic neoplasia. AB - In the concept of MDM, the term melanoma has been reserved for lesions showing a vertical growth component. Vertical growth, divorced from any prognostic implications, is simply a morphologic designation. Such a maneuver also serves to validate the category of MDM, although it might then be inappropriate to characterize such lesions as melanoma. From my view, the modifier "minimal deviation" takes the onus of prognosis out of the equation. For common melanomas, size of a vertical growth component has relativity to prognosis. It is unlikely that, in comparable size-ranges, the MDM have a more aggressive nature than the common melanoma. It seems appropriate to propose that MDM measuring less than 1.5 mm in vertical dimensions could be characterized as melanocytic neoplasia of indeterminant malignant potential. Those less than 1 mm in vertical dimensions would be borderline variants and those in the range of 1 to 1.5 mm would be intermediate examples. Those greater than 1.5 mm could be characterized as melanocytic neoplasias of indeterminant (uncertain) malignant potential without additional qualifications. PMID- 11221514 TI - The shifting patterns of metastatic melanoma. AB - Management of cutaneous melanoma becomes more difficult as tumor cells metastasize to sites that are remote from the primary tumor. There is a hierarchy of risk associated with cancer spread by different routes and to different organs. Differences in clinical outcome indicate critical variations in pathobiology at different stages in disease evolution. Prevention of the evolution of melanoma is critical, especially beyond the stage of nodal involvement. PMID- 11221515 TI - Classification and staging of melanoma. AB - Although a standardized and uniformly accepted cancer staging system is an essential and fundamental requirement to enable meaningful comparisons across patient populations, the sometimes capricious biologic behavior of melanoma makes developing such a staging system particularly difficult. Since the earliest well documented attempts at classifying patients with cutaneous melanoma were described more than 50 years ago, the identification of increasingly powerful prognostic factors has led to sequential modifications of the cutaneous melanoma staging system. The current AJCC staging system is based on relatively well established prognostic factors; however, several recent reports have identified additional prognostic factors not included in the current system, and other studies support the re-evaluation of some of the currently employed staging criteria. Some of the more controversial areas include the relevance of level of invasion versus tumor thickness, optimal cutoffs for tumor thickness, importance of ulceration, the grouping of satellites with in-transit metastases, the inclusion of microsatellites and local recurrences as a separate staging criterion, the replacement of size of nodal mass with number of positive nodes, the importance of nodal metastases in more than one nodal basin, and the prognostic significance of distant metastases. Future modifications of the staging system are anticipated to better incorporate these observations. Stage specific staging recommendations for the patient with melanoma provide the clinician with a framework to most efficiently assess extent of disease in an era of cost-conscious clinical practice. In the asymptomatic patient with primary melanoma (stage I or II), we recommend a chest roentgenogram and evaluation of alkaline phosphatase and LDH levels; extensive radiologic evaluations are not indicated, because the rate of detection in this population is extremely low. Additional staging information should also be obtained by the technique of lymphatic mapping and sentinel lymphadenectomy. For patients with local-regional disease (stage III, satellites, and local recurrence), a selective approach to imaging studies is warranted. For this patient population, we recommend complete blood count, liver function tests including alkaline phosphatase and LDH, a chest roentgenogram, and a CT scan of the abdomen. Although the yield of these tests, particularly CT of the abdomen, in detecting distant metastases in asymptomatic patients is low, they may identify false-positive abnormalities and provide an important baseline for future studies in this high-risk population. For patients with disease below the waist or in the head and neck region, we recommend CT of the pelvis and CT of the neck, respectively. Additional studies should be done only if clinically indicated. Finally, patients with known systemic disease (stage IV) should be more comprehensively evaluated, because the likelihood of detecting asymptomatic metastases is higher. Accordingly, in addition to the work up outlined previously for stage III patients, we also perform a CT scan of the chest and MR imaging of the brain; other studies (e.g., bone scan, gastrointestinal series) are performed on the basis of symptoms. PMID- 11221516 TI - Update of diagnostic and prognostic markers in cutaneous malignant melanoma. AB - The biomolecules described in this article generally have been studied as possible diagnostic or clinically prognostic markers in the context of melanoma disease progression as measured by the gold standards of tumor thickness and development of metastasis. Most of the markers showed variations in expression phenotype only during the deeply invasive or metastatic stage of tumor progression and were thus predictive of clinical outcome only for these subgroups of patients. Some of the markers may have utility in identifying patients with deeply invasive primary tumors who are likely to develop metastasis and thus should receive earlier, more aggressive treatments. In addition, some of the markers may identify patients likely to respond better to a new type of therapy (e.g., anti-angiogenic therapy in a patient whose tumor is overexpressing VEGF or immunotherapy for a patient whose tumor is expressing high levels of MART-1). In the future, it will probably be possible to employ new techniques, such as laser guided microdissection of tissues, to isolate individual melanocytes in order to identify the earliest stage-specific defects that contribute to an aggressive biological behavior. Identifying the subset of patients with superficially invasive melanomas who will develop metastatic disease will continue to provide a challenge. PMID- 11221518 TI - Managing obstructive sleep apnoea. PMID- 11221517 TI - Managing pneumonia in general practice. PMID- 11221519 TI - Passing the MRCGP: a winning strategy. PMID- 11221521 TI - Asthma's link with affluence. PMID- 11221522 TI - A care-home patient with incontinence. PMID- 11221523 TI - What causes asthma and can it be prevented? PMID- 11221524 TI - Key developments in respiratory medicine. PMID- 11221525 TI - Casebook: shortness of breath. PMID- 11221526 TI - Drug treatments and topics: the year in review. AB - In 2000, more than 100 new drugs and devices were approved for use in the United States. Many drugs were reformulated to provide new uses, more effective dosing, or improved costs. In an effort to ensure safe prescribing practices, the Food and Drug Administration has increased drug and device monitoring and services available to clinicians. PMID- 11221527 TI - Avoiding Medicare fraud. Part 2. AB - In 1997, Congress authorized payments to nurse practitioners (NPs) for Medicare provided services. NP services are now reimbursed at 85% of the physician fee schedule. As this source of reimbursement was realized, so was a new area of liability for NPs. Failure to follow billing rules can result in payment denial, repayment of fees already paid, mandated educational activities, fines, fraud prosecution, loss of Medicare-billing ability, and loss of employment. Appropriate billing entails adhering to guidelines for selecting procedure codes and proper medical documentation. This article identifies high-risk areas for NPs who bill Medicare and provides resources for accessing additional information. PMID- 11221528 TI - Treatment options for the menopausal woman. AB - Hormone replacement therapy (HRT) is not benign; its adverse effects can be as serious as the health threats it was designed to prevent. An element of trial and error exists when tailoring a patient treatment regimen. Lack of clinician knowledge and poor clinician-patient communication can result in incorrect or suboptimal HRT decisions. This article presents a comprehensive assessment of options for women entering menopause; recent epidemiologic findings and various HRTs are discussed. PMID- 11221529 TI - Replacing New York State dentists. PMID- 11221530 TI - Focal dermal hypoplasia. Goltz syndrome. A case report. AB - Focal dermal hypoplasia (Goltz syndrome) is a rare syndrome comprising developmental anomalies of tissues and organs of mesoectodermal origin. As a result, there are abnormalities of the eyes, skin, oral structures, musculoskeletal system and central nervous system. This article describes the case of a four-year-old female with focal dermal hypoplasia (FDH) who displayed many of the oral features associated with this syndrome. Her condition was complicated by recurrent episodes of facial cellulitis in relation to skin lesions of the face. This is an unusually severe case of FDH with previously unreported association of cutaneous anomalies and facial cellulitis. PMID- 11221531 TI - A dynasty of doctors. PMID- 11221533 TI - Proper training should precede injections. PMID- 11221532 TI - Answers, please. PMID- 11221534 TI - Seller beware. PMID- 11221535 TI - Support for instruction about homosexuality in South Carolina public schools. AB - Research has demonstrated that recognition of sexual orientation begins in adolescence. However, students who identify as gay or lesbian report that the subject of homosexuality is virtually absent from classroom instruction. In South Carolina public schools, the subject of homosexuality may not be discussed except during instruction about sexually transmitted diseases. In 1997, survey data were obtained from 534 South Carolina registered voters to determine level of support for school-based sexuality education, including support for instruction about homosexuality. Overall, support for sexuality education was strong, however, homosexuality was the least-supported subject in the survey. In addition, registered voters were less sure as to what grade level instruction about homosexuality should begin. Characteristics of voters who supported and opposed instruction about homosexuality in the public schools were examined and compared. These data may be useful in building support for sexuality education programs that address this controversial topic. PMID- 11221536 TI - Patterns of health-risk behavior among Japanese high school students. AB - This study explored patterns of health-risk behaviors among Japanese high school students and examined if a cluster and an accumulation of health-risk behaviors existed. Self-administered questionnaires were employed in 1999 using a sample of 1,466 students (male 50.5%, female 49.5%) in grades 10 through 12 at seven public senior high schools in Okinawa, Japan. Health-risk behaviors studied included cigarette smoking, alcohol use, thinner use, nonuse of seat belts, suicide ideation, sexual intercourse, weight loss practices, and physical inactivity. Among male and female students, cigarette smoking, alcohol use, and sexual intercourse clustered. Accumulation of these risk behaviors also occurred because the observed proportion was greater than the expected proportion assuming independent occurrence. Vocational high school students and upper graders were strongly associated with accumulation of health risk behaviors. These findings identify a high-risk target group among Japanese adolescents and suggest that preventive intervention strategies should take into consideration the cluster and accumulation of health-risk behaviors. PMID- 11221537 TI - The role of academic discipline and gender in high school teachers' AIDS-related knowledge and attitudes. AB - Adolescents represent the fastest growing segment of HIV+ individuals in the United States. Therefore, high school teachers should be both knowledgeable of and comfortable with issues related to HIV/AIDS. This study examined high school teachers' AIDS-related knowledge and attitudes. One hundred forty-one high school teachers from nine central Massachusetts high schools participated. Participants completed the "HIV/AIDS Knowledge and Attitudes Scales for Teachers," as well as questions regarding their teaching experience and academic disciplines. Results indicated a direct relationship between teachers' knowledge of HIV/AIDS and positive or supportive attitudes toward HIV/AIDS. Significant differences were found based on academic discipline, with allied health teachers scoring significantly higher on the knowledge scale than teachers in any other discipline. Specific examples are discussed, as is the need for increased teacher training and comprehensive AIDS education. PMID- 11221538 TI - Health-risk behaviors among middle school students in a large majority-minority school district. AB - Since 1991, the Centers for Disease Control and Prevention has administered the Youth Risk Behavior Survey (YRBS) biennially to representative samples of high school students. YRBS results indicate that health-risk behaviors often developed during middle school years. To date, few state and local education agencies have administered the YRBS-Middle School. This study measured prevalence of health risk behaviors among middle school students in a large, majority-minority school district (n = 1,783). Results indicated that young adolescents (ages 11-14) are engaging in multiple health-risk behaviors. For example, 24.4% seriously considered committing suicide in the previous year, 53.3% had been in a physical fight, 50.2% ever drank alcohol, 17.9% ever used marijuana, and 13.4% had already had sex. Such behaviors potentially could lead to serious consequences related to their educational achievement and overall health status. Health-related policy and program applications are discussed. PMID- 11221539 TI - Addressing the threats of MDMA (Ecstasy): implications for school health professionals, parents, and community members. PMID- 11221540 TI - Creating awareness of the relationship between racial and ethnic stereotypes and health. PMID- 11221541 TI - Asthma outcomes at an inner-city school-based health center. AB - Childhood asthma has reached near-epidemic levels in the US cities. Innovative strategies to identify children with asthma and prevent asthma morbidity are needed. This study measured asthma outcomes after initiation of an inner-city elementary school health center with a schoolwide focus on asthma detection and treatment. The site was an inner-city elementary school in Minneapolis, Minn. The study design incorporated a pre and post comparison with a longitudinal cohort of children (n = 67) and a cross-sectional cohort of children before (n = 156) and after (n = 114) the intervention. Hospitalization rates for asthma decreased 75% to 80% over the study period. Outpatient visits for care in the absence of asthma symptoms doubled (p < .01), and the percentage of students seeing a specialist for asthma increased (p < .01). Use of peak flow meters, use of asthma care plans, and use of inhalers also improved (p < .01). While no change occurred in school absenteeism, parents reported that their children had less awakening with asthma and that asthma was less disruptive to family plans. This schoolwide intervention that included identification of children with asthma, education, family support, and clinical care using an elementary school health center was effective in improving asthma outcomes for children. PMID- 11221542 TI - Biotransformation of 13(Z)-retinoic acid in mouse skin and human keratinocyte cultures. AB - The metabolism of 13-(CIS) in mouse skin in vivo which was treated with TPA (or vehicle) typically showed that the retinoid was oxidized to 4-hydroxy, 5,6-epoxy 13-CIS, 5,8-oxy-13-CIS and undergoes geometric isomerization to RA. Applied 13 (CIS) in human keratinocyte cultures showed that the retinoid was oxidized to 5,6 epoxy-13-CIS, 5,8-oxy-13-CIS, and isomers. Pretreatment with the antioxidant butylated hydroxyanisole(BHA) resulted in a large decrease in formation of the oxirane and increased formation of the alcohol in mouse skin. Proposed mechanisms suggested the involvement of peroxyl radicals and prostaglandin H synthase for the biotransformation of retinoids. PMID- 11221543 TI - The influence of age and gender on HLA-DR in Chinese child-onset type 1 diabetes mellitus patients. AB - To further clarify the association of HLA DR alleles with type 1 diabetes mellitus and the influence of age-onset and gender on type 1 diabetes, we investigated HLA-DR in 76 child onset Chinese (36 males) type 1 diabetes patients and 154 normal controls by using PCR-SSP (sequence specific primer). The mean age of onset of diabetes patients was 8.43 +/- 3.96 year-old. Our results revealed that the frequencies of DR3, DR4 and DR9 in diabetes patients were significantly higher than those in control group (all P < 0.01). The susceptible alleles were DR3, DR4, DR9, with relative risks of 8.25, 2.57 and 2.67, respectively. The protective alleles to type 1 diabetes were DR 2, DR8, DR11 and DR12 with relative risk of 0.24, 0.15, 0.16 and 0.39, respectively. There were no significant differences between the frequencies of HLA DR 3, DR4, DR9, DR3/4, DR3/9 and DR4/9 in male and female diabetic children. We divided the diabetes patients into three groups according to their age of onset (1-5 years old, 6-10 years old and 11-17 years old). There was a trend that the frequencies of DR9 decreased with the increase of age at onset, but there was no significant difference of DR3, DR4, DR9, DR3/4, DR3/9 and DR4/9 frequencies between diabetes children with age onset 0-10 years and 11-17 years. As to the influence of gender on the HLA genotypes, the frequency of DR3/4 decreased with the increase of age at onset for male patients and the frequency of DR3/4 increased with the increase of age at onset for female patients. PMID- 11221544 TI - Craniofacial growth changes of Mongolian children with normal occlusion from 8 to 12 years. AB - The purpose of this study is to quantify the changes of craniofacial skeleton in Mongolian children born in Taiwan. They had normal occlusion and pleasing profiles, received no previous orthodontic treatment, and were aged 8 to 12 years. The subjects included 24 boys and 24 girls from whom lateral cephalograms were taken for the study. After measurements and statistical analysis, the findings in this investigation indicated the following: 1. Although the growth of the mandible showed forward and upward rotation, the growth pattern of craniofacial portion from ages 8 to 12 was stable with no significant difference in angular measurements. Nevertheless, there were significant differences in linear measurements. The linear dimensions exhibited a gradual increase with age for both boys and girls. This fact should be considered in the diagnosis and treatment plan for young patients under 12 years old with anteroposterior discrepancies. 2. There was a considerable degree of sexual dimorphism with boys showing greater angles in the maxilla-mandibular relationship and greater late skeletal and dental changes. Most of the changes in various parameters occurred earlier in girls, and in boys these changes were distributed more evenly over the entire period of study. PMID- 11221546 TI - Ocular manifestations in children with developmental delay preliminary report. AB - To investigate systemic diseases and ocular problems among children with developmental delay, forty-one children (28 boys and 13 girls with a mean age of 3.53 +/- 2.25 y/o) were enrolled in this study. In addition to ocular examinations, we used centrality, steadiness, fixation and flash visual evoked potentials (VEPs) tests on all of the children. We found that 23 children (56.10%) had ocular problems with optic atrophy and strabismus being the two most common ocular abnormalities. The two major clinical manifestations of developmentally delayed children were mental and motor retardation. The primary test of centrality, steadiness and fixation and visual evoked potentials could be useful tools in evaluating the visual pathway and ocular motility. Preliminary results showed that more than half of the children with developmental delay had certain ocular abnormalities. The high incidence of ocular abnormalities deserves careful attention when these children are brought to seek medical help. Further study of ocular problems among developmentally delayed children and a search for more reliable examination method should be encouraged. PMID- 11221545 TI - Familial breast cancer in southern Taiwan. AB - The purpose of this study is to evaluate whether there are pathobiologic differences and differences in overall rates survival between familial and non familial breast cancer patients in Taiwan. A retrospective study was performed evaluating 76 familial breast cancer patients in 69 families, which included two BRCA1 related cases and six BRCA2 related cases. Patients were compared with 425 non-familial sporadic cases. Familial breast cancer patients had similar ages and stages as non-familial patients (mean, 46.6 years vs 48.9 years, p = 0.306). However, the familial breast cancer patients with BRCA1 and BRCA2 related cases presented at lower stages (p = 0.034) and younger ages than non-familial patients (mean, 45.1 years vs 48.9 years P = 0.042). The occurrence of infiltrating ductal carcinoma and lobular carcinoma in situ was not significantly different in the two groups. Mucinous carcinoma was represented with 6.7% (4/76) and 1.3% (1/76) medullary carcinoma. The overall grade of familial breast cancer, including BRCA1 and BRCA2 related cases in 8 infiltrating ductal carcinoma, was significantly higher than that of controls. The mean follow up was 4.5 years for familial breast cancers. Five- and 10-year overall survival rates were 69% and 61% for those with a family history, compared with 86% and 64% for those in the control group (p = 0.644). There were no statistically significant differences in disease free survival rates between the two groups at 5 or 10 years (69% vs 78% in 5 years; 48% vs 58% in 10 years) (p = 0.862). Despite the younger ages and earlier stages at presentation in familial breast cancer patients with BRCA1 and BRCA2 related cases, the familial breast cancer patients had higher grade patholobiologic characteristics, but similar prognoses when compared with sporadic breast cancer patients. Owing to the limited number of familial cases in this study, more cases and longer follow up are needed. PMID- 11221547 TI - Focal cerebral hyper-perfusion in phantom limbs: assessed by Tc-99m HMPAO SPECT. AB - Phantom limb pain is a common experience for patients who have received amputation. However, the definite mechanism is still not clear. Here, we describe a patient who suffered from phantom limb pain after left above-elbow amputation. The Tc-99m hexamethylpropylene amine oxime (HMPAO) brain single photon emission computed tomography (SPECT) study revealed increased regional cerebral blood flow in the right parietal cortex. This finding may imply the involvement of cerebral cortex in the development of phantom limb pain. Further study is worthwhile to elucidate the utility of SPECT and the role of cortex in phantom limb pain. PMID- 11221548 TI - Peritoneal scintigraphy for diagnosing periumbilical leakage in a patient on continuous ambulatory peritoneal dialysis. AB - Continuous ambulatory peritoneal dialysis (CAPD) offers several advantages over hemodialysis for patients with end-stage renal disease; however, this technique also includes many documented complications. A case with clinical suspicion of dialysate leakage on CAPD was investigated by peritoneal scintigraphy using technetium-99m macroaggregated human albumin (99mTc-MAA). Peritoneal scintigraphy showed radiotracer accumulation over the periumbilical area at 2 hours 30 minutes after intraperitoneal infusion of 99mTc-MAA. Six hours of imaging revealed more apparent radioactivity at the same site. This study is to illustrate the simple diagnostic helpfulness of peritoneal scintigraphy in a patient with a CAPD related structural defect. PMID- 11221549 TI - Peripheral retinal angioma presenting as macular pucker--case report. AB - A 36-year-old Taiwanese male, who denied any history of ocular trauma, intraocular inflammation or surgery, had a macular pucker associated with a peripheral retinal angioma. The yellow-white macular pucker, which extended from the temporal disc to the macular area, was thicker and with more prominent retinal striaes than found among the elderly. Regression of the macular pucker did not occur with incomplete laser photocoagulation of the angioma. Retinal angioma should be considered in the differential diagnosis of macular pucker without posterior vitreous detachment (PVD) in healthy young patients. Management of this association is primarily complete obliteration of the angioma. PMID- 11221550 TI - [Development of neurobiology effects the future of psychotherapy]. PMID- 11221551 TI - [Prospects in psychotherapy research]. AB - The point of departure for this discussion is a critical review of the philosophy of randomized controlled trials (RCT) and their specific errors when applied to psychotherapeutic methods. There is a gap between the highly artificial settings of psychotherapy RCT and naturalistic psychotherapy procedures, which are grounded more in personality than in technique, less regulated, and mostly eclectic. Although RCT are necessary for general assessments of efficacy, they should be complemented by efficiency studies and evaluation of whole health care systems which include psychotherapy. We argue against overstretching the analogy of good clinical practice (GCP) research for the purpose of admitting new psychotropic drugs to psychotherapy research. A rational approach to psychotherapy for indication, quality ascertainment, and allocation of resources needs research which is methodologically explicable, replicable, and relevant to practice. The Cochrane Collaboration is a means of distributing such knowledge and making it work for practitioners. However, Cochrane also sheds light on psychological and practical obstacles which must be overcome before public health care systems can utilize new scientific results. The discussion of disorder specific psychotherapy versus general psychotherapy ends by emphasizing the importance of more detailed psychopathology and pathopsychology of dysfunctions that cannot be sufficiently explained in manuals. Such dysfunctions--not necessarily specific for diagnoses or abnormality at all--can then be matched to specific psychotherapy tools. Further innovations can be expected from neurosciences, and some of the most promising paradigms are discussed. Finally, the lasting importance of hermeneutics is stressed not only with regard to the generation of new hypotheses but also to guiding the psychotherapeutic process. PMID- 11221552 TI - [What is science-based psychotherapy? On the discussion of guidelines for psychotherapy research]. AB - The scientific nature of psychotherapy can be defined by two partially interrelated criteria: validity of the theory underlying a therapy and efficacy or effectiveness of a therapy. To enhance the scientific basis of a psychotherapeutic approach, research is needed on therapeutic objectives, principles, and processes, measuring methods, process-outcome relationships, and efficacy and effectiveness of therapies. Determination of efficacy requires randomized clinical trials (RCT). The scientific basis must be seen as the continuous development of a psychotherapeutic approach. In contrast, the question of whether a psychotherapeutic approach is well established is dichotomous. In addition to scientific criteria, those deriving from mental health policy and economics are also important. This paper presents various approaches to ascertaining efficacy. According to the criteria of the American Psychological Association Task Force, to be "well-established," treatments for specific disorders must be shown efficacious in at least two independent randomized clinical trials. Although comparability is limited, we propose that psychotherapeutic research be conceptualized into phases, as in pharmacotherapeutic research. PMID- 11221553 TI - [Experience guided neuronal plasticity. Significance for pathogenesis and therapy of psychiatric diseases]. AB - Whereas the basic wiring of the mammalian central nervous system is genetically predefined, its fine tuning throughout different phases of infancy, childhood, and adulthood are highly experience-dependent. There is growing evidence from a variety of experimental data that juvenile experience and learning events modulate the functional maturation of the brain, thereby shaping the neuronal substrate for the development of intellectual and socioemotional capacities. Since early experiences occur during phases of elevated neuronal and synaptic plasticity, they induce an "imprinting" of synaptic connectivity and neural circuitry in the infant brain. Results from experimental research support the hypothesis that impoverished intellectual stimulation and traumatic socioemotional experience during early childhood may impair the formation of functional brain pathways, in particular of the limbic circuits, which play a major role in emotional behavior and learning. Such defective systems, representing functional "scars" in the brain, may be the neuronal basis of a variety of mental disorders and clinical symptoms caused by early stressful psychosocial environments. A basic thesis of this paper is that mechanisms involved in neuronal learning and memory are not only used and reused in structuring the CNS during the initial establishment of connections in the immature brain but also can be employed in molding personality and behavior during psychotherapy in adulthood. PMID- 11221554 TI - [Conflict-centered individual therapy or integration of psychotherapy methods. Process of change in client-centered psychotherapy with and without behavioral exposure therapy in agoraphobia with panic disorder]. AB - The mechanisms of change due to different psychotherapeutic treatments of anxiety disorders are the subject of the present study. Sixty-eight patients with agoraphobia and panic (DSM III R No. 300.21, ICD 10 No. F 40.01) were included, exclusively treated with client-centered treatment (n = 28) or with additional behavioral exposure treatment (n = 40) in an inpatient setting. The patients were examined on admission, at discharge, and at 6 and 12 months follow-ups with the Structured Clinical Interview for DSM III R (SKID), the Freiburg Personality Inventory (FPI R), and the Giessen Test (GIESS). Both treatment modalities significantly reduced panic and avoidance. Differences were found in personality scales. The support of autonomy was superior by client-centered treatment alone: client-centered treated (CCT) patients felt less dependent on the expectations of others, less under stress, and had fewer psychosomatic complaints. Patients with additional exposure treatment feel accepted by their social environment earlier. The results are discussed with regard to open questions of therapy integration and different mechanisms of change. PMID- 11221555 TI - [Computer-assisted patient survey as the basis for modern quality assurance in psychiatry. Results of pilot studies]. AB - We report on a novel computer system for psychiatric patients that runs an interview procedure on the outcome and quality of care (e.g. well-being, mood, satisfaction with treatment). Patients are asked to perform the interviews on a daily basis and on their own initiative. The information is meant to provide feedback to the therapeutic team. In the pilot studies we investigated the feasibility and acceptance of the computerised interviews. Four computer systems with touchscreen input were integrated into the routine of an open inpatient ward and of the day hospital of a psychiatric university clinic for a period of 17 weeks. The patients' attendance and the acceptance of the interviews were good. Patients were able to interact with the touchscreen terminals without greater problems. Accurate and valid data were recorded. Because of some problems with the administration of the patients' identification numbers we develop suggestions how to improve the computer systems. Possible applications of the computerised interview system in quality assurance and research are discussed. PMID- 11221556 TI - [Non-fatal effect of highly toxic amitriptyline level after suicide attempt. A case report]. AB - Pharmacotherapeutic intervention in psychiatric patients often bears the risk of drug abuse for suicide attempts. Especially intoxication with tricyclic antidepressants, e.g., amitriptyline, may cause severe complications such as cardiac arrhythmia. Even under intensive care conditions, 2-3% of intoxicated patients still die. Here, we report on a depressed female patient who, thanks to timely and intense intervention, survived a suicide attempt with amitriptyline despite highly toxic plasma levels. PMID- 11221558 TI - [The concept of evidence-based medicine in psychiatry]. PMID- 11221557 TI - [Therapeutic effectiveness. Effects, effectiveness and value of therapeutic interventions]. AB - Terms such as efficacy and efficiency of treatment are presently taking on growing importance for medical practice. Two examples are the increasing limitation of cost reimbursement to evidence-based, scientifically proven therapeutic measures and assessment of efficiency in terms of budgeting. We briefly discuss the definition and application of important terms and concepts in this context and ethical and methodological problems involved. PMID- 11221559 TI - Bovine spongiform encephalopathy (BSE). PMID- 11221560 TI - 'Defence' against emergency diseases. PMID- 11221561 TI - Trying to contain antibiotic resistance. PMID- 11221562 TI - Revised hens policy another AVA cop-out. PMID- 11221563 TI - Use of anticholinergics in veterinary anaesthesia. AB - This viewpoint examines the time-honoured and popular use of anti-cholinergics in veterinary anaesthesia. The disadvantages of routine use and specific indications for the use of these useful drugs are discussed. PMID- 11221564 TI - Preanaesthetic use of atropine in small animals. AB - Although it is unwise to recommend any preanaesthetic drug or regimen to be used routinely without consideration for the individual patient, the procedure being undertaken or the other drugs that will be used during the anaesthetic, of all anaesthetic-related drugs that might be under review, atropine is probably one of the least 'toxic' and least likely to cause life-threatening complications when used correctly. In most small veterinary practices there isn't the luxury of a dedicated anaesthetist available to monitor and manage each anaesthetised patient and the best form of cardiac monitor available may be an audible rate monitor. In this situation the advantages combined with the usual indications probably far outweigh the disadvantages of using atropine prophylactically. If a choice must be made, a sinus tachycardia under anaesthesia is probably preferable to a profound bradyarrhythmia. Absolute contraindications for using atropine are rare; the drug, when used alone, has low incidence of toxicity at clinically recommended doses in dogs and cats. Further, the new inhalation agents available to veterinarians (enflurane and isoflurane) do not sensitise the heart to the effect of catecholamines, so that the predominance of sympathetic tone produced when atropine is used is unlikely to precipitate dysarrthythmias during gaseous anaesthesia. Rhythm disturbances that occur under halothane anaesthesia when atropine is used, suggest there is some other cause, or agent, that is arrhythmogenic, such as an alpha 2 agonist, excessively deep level of anaesthesia, hypercapnia or hypoxaemia. Notwithstanding the above arguments, my preference, as a specialist anaesthetist, is that a drug is given only as required (not before) and that when, for example, any unusual heart rhythm occurs, all possible reasons for the occurrence (such as excessively deep anaesthesia or hypoventilation) are eliminated before other drugs like atropine or antiarrhythmics are administered. PMID- 11221565 TI - Surgical arthrodesis of distal tarsal joints in 17 horses clinically affected with osteoarthritis. AB - OBJECTIVE: To evaluate the outcome of 17 horses that underwent surgical arthrodesis of the tarsometatarsal and distal intertarsal joints for treatment of lameness due to osteoarthritis. DESIGN: Retrospective clinical study using client owned animals. PROCEDURE: Horses with hindlimb lameness were diagnosed with osteoarthritis of the distal tarsal joints following relief of lameness after intra-articular anaesthesia or intra-articular corticosteroid injection. Surgery to stimulate ankylosis was performed on 27 hocks by placing 3 diverging 3.2 mm drill holes approximately 3 cm through the tarsometatarsal and distal intertarsal joints from the medial aspect of the limb. The results of surgery were assessed by postoperative examinations, telephone communication with clients and analysis of race results. RESULTS: In 71% of horses, surgery was considered to be successful as determined by clinical examination or telephone communication with clients: six of these horses had unilateral surgery and six had bilateral surgery. This represented 85% (6/7) of horses undergoing unilateral surgery and 60% (6/10) of horses having bilateral surgery. All (8/8) racing Standardbreds and 67% (4/6) of racing Thoroughbreds were considered a success. The average time between surgery and a return to racing was 9.5 months. CONCLUSIONS: The surgical technique used here can provide resolution of lameness from osteoarthritis of distal tarsal joints with a success rate similar to other reported surgical arthrodesis techniques that are more invasive and have a greater morbidity. PMID- 11221566 TI - Treatment of canine leproid granuloma syndrome: preliminary findings in seven dogs. AB - OBJECTIVE: To determine effective treatment strategies for patients with refractory canine leproid granuloma syndrome. DESIGN: Multi-institutional retrospective/prospective case series using client-owned dogs. PROCEDURE: Seven dogs (four Boxers, one Dobermann, one Bullmastiff and one Bullmastiff cross-bred; ages 3 to 11 years) with leproid granulomas were treated successfully using a variety of treatment regimens. These cases were recruited because: lesions were either widely distributed over the dog; progressive, despite routine therapy, or were associated with particularly disfiguring lesions. The treatment regimen evolved during the course of the clinical study. RESULTS: Combination therapy using rifampicin (5 to 15 mg/kg p.o., every 24 h) and clarithromycin (8 to 24 mg/kg p.o. daily; dose divided every 8 or every 12 h) was used most frequently and proved to be effective and free from side effects. Total daily doses of clarithromycin in excess of 14 mg/kg were considered optimal and long treatment courses, in the order of 1 to 3 months, were used. Combination therapy using rifampicin (25 mg/kg; that is, higher than the recommended dose) and clofazimine was effective in one case, but resulted in hepatotoxicity. A topical formulation of clofazimine in petroleum jelly was used as an adjunct to oral rifampicin and doxycycline in another patient treated successfully. CONCLUSION: Based on our evolving clinical experience, a combination of rifampicin (10 to 15 mg/kg p.o., every 24 h) and clarithromycin (15 to 25 mg/kg p.o. total daily dose; given divided every 8 to 12 h) is currently recommended for treating severe or refractory cases of canine leproid granuloma syndrome. Treatment should be continued (typically for 4 to 8 weeks) until lesions are substantially reduced in size and ideally until lesions have resolved completely. A topical formulation, containing clofazimine in petroleum jelly may be used as an adjunct to systemic drug therapy. Further work is required to determine the most cost effective treatment regimen for this condition. PMID- 11221567 TI - Eisenmenger's complex in a Holstein-Friesian cow. AB - A 4.5-year-old, Holstein-Friesian cow presented with a 1-month history of severe exercise intolerance. Rectal examination and transrectal ultrasonography revealed a large mass in the left retroperitoneum. The heart rate was 70 to 80/min. Premature ventricular complexes and ventricular bigeminy were present on an electrocardiogram. Erythrocytosis was present and blood gas analysis revealed marked hypoxaemia. An echocardiogram demonstrated a large ventricular septal defect, a partially dextroposed aorta, and concentric hypertrophy of the right ventricular free wall. Colour flow Doppler echocardiography and a contrast echocardiographic study demonstrated a right-to-left shunt through the ventricular septal defect. Eisenmenger's complex was diagnosed. The patient was euthanased. Necropsy confirmed the gross cardiac lesions identified by echocardiography and an abscess in the apex of the left ventricle. Severe pulmonary arterial lesions were present, consistent with a marked increased in pulmonary vascular resistance. Actinomyces pyogenes was cultured from abscesses of the retroperitoneum and the ventricular apex. PMID- 11221568 TI - Characterisation of lymphosarcomas in Australian cats using polymerase chain reaction and immunohistochemical examination. AB - OBJECTIVE: To examine tumour tissue of cats with lymphosarcoma for the presence of feline leukaemia virus and feline immunodeficiency virus and analyse the immunophenotype of the tumours. DESIGN: A retrospective study of feline lymphosarcoma cases. METHODS: Formalin-fixed, paraffin-embedded tumour tissue of 14 feline lymphosarcomas was examined for the presence of feline leukaemia virus and feline immunodeficiency virus by polymerase chain reaction and immunohistochemistry. Using polyclonal and monoclonal antibodies against T and B lymphocytes, the phenotypic expression of the tumours was characterised. RESULTS: No feline leukaemia virus antigen or proviral sequences were detected. Feline immunodeficiency virus proviral sequences were detected in two cases by polymerase chain reaction. Immunophenotyping of all 14 cases resulted in seven cases being classified as B-cell phenotype, four as T-cell phenotype, and the remaining three undetermined. CONCLUSIONS: In contrast to previous reports overseas, our results suggest that feline leukaemia virus infection appears to be an infrequent cause of lymphosarcoma in the cats that were necropsied. Feline immunodeficiency virus may have a role in lymphomagenesis. The potential role of feline immunodeficiency virus needs to be explored in more depth. Compared with most previous reports, B-cell tumours were more common than T-cell tumours in this series of cats. PMID- 11221569 TI - Comparison of DNA probe test and cultivation methods for detection of Mycobacterium avium subsp paratuberculosis in caprine and ovine faeces. AB - OBJECTIVE: To compare a DNA probe test with two cultivation methods for the detection of Mycobacterium avium subsp paratuberculosis in goat and sheep faeces. DESIGN: Comparison of the results of the three methods with histological examination as the reference standard. PROCEDURE: Faecal specimens were obtained from goats and sheep originating from flocks known to be affected with paratuberculosis and tested for Mycobacterium avium subsp paratuberculosis with a DNA probe test and two cultivation methods (old conventional culture and new double incubation method in Herrold's and Lowenstein-Jensen medium). RESULTS: In goats, the sensitivity of the various tests were for the DNA probe test 17.2%, for the double incubation culture method 25.4% and for the old conventional culture method 22.8% using the histopathological results as reference. In sheep the sensitivity of the various tests were for the DNA probe test 13.2%, for the double incubation culture method 8.8% and for the old conventional culture method 5.9% using the histopathological results as reference. The specificity of the above tests was 100% in goats and sheep and the specificity of the double incubation culture method in goats was 91%. CONCLUSIONS: The DNA probe test is a rapid and specific test that could be used in a control program if the sensitivity of the test were improved and possibly in combination with another test. PMID- 11221570 TI - Our first anti-docking law already in place! PMID- 11221571 TI - Prevention of blowfly strike on coarse and fine woolled sheep with the insect growth regulator dicyclanil. AB - OBJECTIVE: To assess a ready-to-use formulation of dicyclanil to prevent blowfly strike on coarse and fine woolled sheep under New Zealand conditions. DESIGN: Randomized clinical field trials. PROCEDURE: In a first field trial, coarse wooled sheep treated with a ready-to-use, 5% dicyclanil formulation were compared with untreated control sheep for up to 21 weeks. In a second field trial, fine woolled sheep, treated with the same dicyclanil formulation, were compared with untreated sheep for up to 19 weeks. Efficacy was assessed by calculating the aggregated cumulative strike rate. RESULTS: For trial 1 (coarse woolled sheep) the aggregated cumulative strike rate at the end of the trial at week 21 after treatment reached 3.9% and 19.1% for treated and untreated sheep, respectively. For the treated animals the aggregated cumulative strike rate reached the 1% and 2% benchmarks between weeks 11 and 12. For trial 2 (fine woolled sheep) the aggregated cumulative strike rate at the end of the trial at week 19 reached 0.6% and 7.5% for treated and untreated sheep, respectively. Wool length at the time of application did not substantially influence the efficacy of dicyclanil. CONCLUSION: Under New Zealand field conditions, a ready-to-use 5% spray-on formulation of dicyclanil protected coarse woolled sheep for at least 12 weeks and fine woolled sheep for at least 19 weeks. PMID- 11221572 TI - Cardiovascular and haemodynamic effects of intramuscular doses of xylazine in conscious sheep. AB - OBJECTIVE: To determine if a commonly used analgesic dose of xylazine has detrimental cardiovascular or haemodynamic effects in sheep. DESIGN: A physiological study following intramuscular administration of xylazine. PROCEDURE: Xylazine (50 micrograms/kg) was injected intramuscularly into six healthy Merino ewes. For 60 min heart rate, mean arterial blood pressure and cardiac output were recorded; arterial blood samples for the measurement of blood gas tensions were also collected. RESULTS: There were no significant changes in heart rate, mean arterial blood pressure, cardiac output or arterial carbon dioxide tension. A slight degree of arterial hypoxaemia was noted with a 10% reduction in arterial oxygen tension values at 30 min. CONCLUSION: The minimal changes to cardiovascular and respiratory values in this study verify the safety of previously suggested analgesic dosing regimens for sheep. Previously reported hypoxaemic effects in sheep as a result of intravenous xylazine administration appear to be reduced as a result of intramuscular administration. PMID- 11221573 TI - Inclusions in the erythrocytes of eastern water dragons (Physignathus lesueurii). PMID- 11221574 TI - Family risk and resiliency factors, substance use, and the drug resistance process in adolescence. AB - Recent approaches to drug prevention have emphasized risk and resiliency factors. Two models have been developed to explain these factors, one which posits that separate elements make up each set and the other which posits that a single factor can be either a risk or a resiliency factor depending on, for example, if it is present (resiliency) or absent (risk). This study tested these models and attempted to compare the effects of risk and resiliency across gender and ethnicity. Results support the model in which risk and resiliency are discrete sets of factors and demonstrate that overall resiliency factors play a larger role than risk factors in substance use and drug resistance processes. However, gender proved to be an important moderator of these effects. For adolescent males, resiliency has an indirect effect on overall substance use through age of first use, while risk has a direct effect on overall substance use. For adolescent females, resiliency has a direct effect on overall substance use and risk has an indirect effect through age of first use. This indicates that while early interventions are important for both genders, resiliency factors must be dealt with before initiation of substance use for males. Findings did not differ substantially across ethnicity, although the small African-American sample size may have limited power to detect differences. PMID- 11221575 TI - Interactive multimedia preventive alcohol education: a technology application in higher education. AB - This article summarizes the process of implementation and short-term impact on knowledge and attitudes of an interactive multimedia software program on preventive alcohol education for young adults. The three factors related to behavioral change addressed in the software are self-efficacy in maintaining personal control and safety while using alcohol, attitudes and related expectations regarding the physiological and behavioral consequences of alcohol consumption, and peer norms regarding alcohol consumption. As compared to alternative alcohol education and a no-alcohol education groups, students using the interactive computer lesson reported learning more about dose-response and ways to intervene with friends in peril. The article concludes with consideration of the import of this technology for informing students about the consequences of alcohol use, and the utility to higher education institutions of using this technology in an era when pressures increase for due diligence around student safety but with few additional institutional resources. PMID- 11221576 TI - Methamphetamine use: hazards and social influences. AB - Use of methamphetamine, a potent central nervous system stimulant, increased in the early- to mid-1990s in the United States, concentrated in the west, midwest, and south. The use and trade of methamphetamine was facilitated by a fairly simple production process and the involvement of numerous small entrepreneurs as well as drug-trafficking syndicates. National data from the 1994 Drug Abuse Warning network revealed that for the period from 1991 to 1994 methamphetamine use among short-stay hospital patients more than tripled, and methamphetamine related deaths reported by medical examiner offices nearly tripled. In addition, the Treatment Episode Data Set revealed a 43 percent increase in treatment program admissions in which clients identified methamphetamine as the primary drug of abuse. Nonetheless, methamphetamine use did not become widespread in the U.S. population. Low-income and unemployed young white men continue to be the group most likely to use methamphetamine, but by the mid-1990s the drug had increased in popularity in more diverse populations and regions. Economic and social pressures experienced by a broad array of Americans may partially explain expanded methamphetamine use; for example, depressed economic conditions in rural and semi-rural areas have contributed to methamphetamine's appeal as a source of income. A "war against drugs" approach has characterized the policy response, with increased criminal justice penalties. A public health approach is recommended, including prevention campaigns, harm-reduction outreach and treatment approaches, and pharmacologic and abstinence-based drug treatment approaches. PMID- 11221577 TI - Physical training as a substance abuse prevention intervention for youth. AB - Program evaluation data from school and community applications of a physical fitness drug prevention program is presented. A train-the-trainer methodology was applied to install the program in twenty-two settings within the state of Illinois. The physical training program consisted of exercise and educational modules delivered over a twelve-week time period that focused on learning values and life skills through exercise. Complete pre-post data were obtained on 329 participating youth at six school and community based sites. Significant increases were demonstrated in physical activity and physical fitness (cardiovascular endurance, strength, and flexibility). Youth self-report data indicated significant decreases in risk factors such as low self-concept, poor school attendance, anxiety, depression, and number of friends who use alcohol and drugs. There were significant reductions in the percentage of youth who used cigarettes, smokeless tobacco, and alcohol. It was concluded that a strong relationship was demonstrated for increased fitness leading to lowered risk factors and usage patterns. Likewise, the train-the-trainer model was shown to be an effective installation approach to expand fitness programming within prevention settings. PMID- 11221578 TI - News coverage of alcohol and other drugs in U.S. college newspapers. AB - This study investigated the substance use-related content of a sample of student run college newspapers. Two independent coders examined 157 news stories, features, editorials, commentaries, letters, photographs, and cartoons. Items about alcohol appeared in one out of every two issues, while items about other drugs appeared in one out of every five issues. Basic information about alcohol and other drug (AOD) use was reported in about one-fifth of the items, while three-fourths dealt with social, legal, safety, or health problems associated with AOD use, especially alcohol consumption. Just over half referred to some type of control policy, most often an enforcement action. Around one-fourth mentioned educational efforts to promote AOD prevention. Very few dealt with detection, intervention, or treatment. Most college newspapers are missing good opportunities for more extensive coverage of AOD issues that would better inform their readers, especially about factors contributing to campus AOD problems and specific program and policy options. PMID- 11221579 TI - Boater training, drinking and boating, and other unsafe boating practices. AB - OBJECTIVES: Identify associations between lack of formal boater training, drinking and boating, and other unsafe boating practices. METHODS: A telephone survey queried respondents (age 16 or older in continental United States) about boating experience, type of boat used, and training. RESULTS: Of the 3,042 boaters surveyed (70% response), most had no formal training (73%). Boaters with formal training failed to use PFDs about as often as those without formal training and were equally or more likely to use alcohol while boating. CONCLUSIONS: The unexpected association between formal training and unsafe boating practices is probably due to reduced risk perception and inadequacies of boater training programs. Such programs seldom mention the risks of alcohol use while boating. Decisions to mandate formal training should be informed by these results; if mandated, training should address the risks of alcohol use while boating, and should be renewed frequently enough to offset reductions in risk perception. PMID- 11221580 TI - Isozyme diversity in cassava cultivars (Manihot esculenta Crantz). AB - Isoenzyme electrophoresis was used as a method to determine genetic diversity in various M. esculenta cultivars collected in the Southwestern (SW) and Northwestern (NW) regions of the State of Parana, in the South region of Brazil, and in cultivars produced at the Agronomic Institute of Campinas (IAC), Sao Paulo State, Southeastern region of Brazil. The cultivars have been maintained by vegetative propagation for 5 years and are useful in production programs. A total of 28 loci in the acid phosphatase (ACP; EC 3.1.3.2), esterases (EST; EC 3.1.1.1), malate dehydrogenase (MDH; EC 1.1.1.37), and shikimate dehydrogenase (SKDH; EC 1.1.1.15) isozymes was analyzed. The proportion of polymorphic loci for NW, SW, and IAC cultivars was 57.14, 50.0, and 53.6% respectively. Genetic diversity calculated by Nei's genetic identity (I) showed high I values for the three M. esculenta subpopulations. The high degree of polymorphism expressed by cassava cultivars is highly relevant to stimulate breeding programs with M. esculenta species. PMID- 11221581 TI - Secondary analysis of perceptions and meanings of type 2 diabetes among Mexican American women. AB - PURPOSE: The purpose of this study was to explore explanatory models of diabetes from the perspective of Mexican American women with type 2 diabetes. METHODS: In depth interviews were conducted in a secondary analysis of an interpretive interactionism study to investigate the meanings of diabetes from the perspectives of Mexican American women with type 2 diabetes. The sensitizing concept used was Kleinman's explanatory models of illness. The original study sample included 20 Mexican American women between the ages of 27 and 45 with varying lengths of time since diagnosis. RESULTS: Data analysis was an interactive process. The data were collapsed into explanatory models of diabetes categorized as defining, getting, having, describing, or taking care of diabetes. The meaning of having diabetes was viewed as a life threat with complications and a shortened life. CONCLUSIONS: Diabetes complications, viewed as symptoms, were structured in the explanatory models developed from the contextual arenas of family and community. Given the family and community history of diabetes, genetic predisposition to the disease, and perceived life threat, understanding Mexican American women's explanatory models about diabetes serves as a basis for negotiating therapeutic interventions. PMID- 11221582 TI - [The ANMCO (National Association of Hospital Cardiologists) in a changing health care system. Consensus development of the Organizing Symposium of the XXXI National Congress of Cardiology--ANMCO; Florence, May 21, 2000]. AB - This year's symposium, while following the 30-year-old tradition of Organizational Symposia which have become a trademark of the National Association of Hospital Cardiologists (ANMCO) annual meetings, is characterized by a novel approach in terms of method and content. Prompted by the profound changes affecting the socio-cultural, organizational and economic context in which the Health Service operates, the Board of the Association decided to invite the community of hospital-based cardiologists to reflect on and make proposals concerning a number of leading topics not strictly related to the organization of hospital-based cardiology, but of a wider relevance pertaining to the whole issue of the relationship between a Scientific Society and the other components of the Health Service: national and regional institutions, other doctors, the lay public and the pharmaceutical industry, etc. The main aim of this exercise was to stimulate the Society to adapt to a changing environment and so render it more capable of effectively fulfilling its duties. Naturally the larger the consensus regarding the strategies to adopt the greater this efficacy will be. Out of the many possible subjects, four were chosen as preeminent: 1. ANMCO and research: what fields of research should be prioritized, and with what kind of internal organization, and external relations? 2. ANMCO and professional training: what should be the professional standards governing the cardiologist in a changing society, what strategies for continuing education and institutional accreditation? 3. ANMCO and the community-based Health Service: the need to establish clear and efficient organizational relations with community-based cardiology and especially with general practitioners, in order to ensure that the health service is in tune with the real world, guarantee real continuity of care and reduce unnecessary hospital admissions; 4. ANMCO and the general population: how to support the citizen-user in the imperfect health-market, how to first inform the patient and then guarantee true freedom of choice, how to respect the values of the patient, transcending ideological limits and proposing organizational solutions and a return to ethical guidelines. In order to be able to approach topics of this importance and complexity with some probability of success it is fundamental that a proper consensus is reached among the cardiological community which formulates and attempts to carry out any proposed strategy. Working hypotheses designed by a minority of the Society, even if authoritative, and "imposed" on the majority are destined to have a difficult and short life. These premises gave rise to the innovative method characterizing this Symposium: each of the four topics, once identified, was assigned to an expert member who produced a preliminary draft including some proposals. These drafts were circulated to all members of the Association some months prior to the conference, in order to allow for any new comments, proposals and criticisms. This interaction with the members allowed us to collect grass-root opinions which were then organized into their respective topics by one discussant for each topic, who acted as spokesman at the conference. During the Symposium the expert member for each topic summarized his proposals and initial thoughts (already known to all members) while the discussant represented the opinions of the members; finally each topic was open to debate. The last step of this complex procedure was a meeting of the symposium panel made up of the chairmen, speakers and discussants who drafted a consensus document representative of all the opinions discussed at the Symposium. What follows is the consensus document on the four chosen topics for the general information of all the members and for proposal to the Board of the Society who will take the executive decisions. Chapter 1. The speed with which technology is improving and medical knowledge increasing is creating a gap between biological research and clinical research and another gap between clinical research and its application in daily practice. The task any medico-scientific society must set itself is to bridge these gaps by integrating research and the diffusion of its results - i.e. training. ANMCO actively carries out both functions but lacks the organs which could produce far reaching scientific research strategies. This document reports the aims and ways of resolving this structural problem. Chapter 2. Continuing medical education aimed at maintaining and developing the knowledge of a medical professional, represents a cultural requirement and now it has become a legislative duty also in Italy. During a symposium held on the occas PMID- 11221583 TI - [Interactions between physical training and pharmacologic treatment in the prevention of ventricular remodelling in patients with left ventricular dysfunction]. AB - Exercise training is a recommended treatment for chronic heart failure. So far, randomized clinical trials showed that exercise training can improve peak oxygen consumption and reduce neurohormonal and adrenergic activation, nevertheless, the effect on left ventricular remodeling is still controversial. The present study reviewed the randomized clinical trials that investigated the effects of exercise training on left ventricular remodeling. After a first study that showed a worsening of left ventricular function, the following studies showed a neutral effect, and finally, the ELVD-CHF study showed both a reduction in left ventricular dilation and an improvement of ejection fraction. These different results could be explained by the pharmacological treatment before exercise training: in the first study patients did not assume ACE-inhibitors, in the following studies most patients assumed ACE-inhibitors and, finally, in ELVD-CHF, patients assumed ACE-inhibitors and about one fifth of them were on beta-blockers too. In conclusion, exercise training may improve peak oxygen consumption and reduce neurohormonal and adrenergic activation in patients with chronic heart failure. Further studies are necessary to assess if exercise training, associated with ACE-inhibitors and beta-blockers, can reverse or prevent left ventricular remodeling. PMID- 11221584 TI - [Single-lead DDD cardiac pacing: state of the art and future perspectives]. AB - The electrical treatment of advanced atrioventricular block, with normal sinus node function, can be successfully and safely performed with single-lead atrial floating electrode VDD pacing. In comparison with two-lead DDD pacing, it offers some important advantages: easier and less time-consuming implantation procedures, simpler follow-up controls, and lower medium and long-term complication rates. However, should sinus node dysfunction develop, the atrium cannot be paced with this special kind of cardiac stimulation. For this reason, in the last few years, a particular research field has developed to overcome this problem. In this paper, the literature is reviewed, with special attention to the studies analyzing the commercially available leads and some prototypes implanted, outlining the pros and cons. The high stimulation energy, the inconstant atrial capture, and phrenic nerve stimulation are still unresolved problems. The reliability and efficacy of single-lead DDD pacing will presumably depend, in the future, on the development of preshaped, new-designed electrodes, with stable contact with the atrial wall, and on new stimulation waveforms. In this context, however, particular attention should be devoted to the correct atrial signal detection. PMID- 11221585 TI - [Digital revolution in the echocardiography laboratory. Current status and future perspectives] . AB - Echocardiography is changing from an operative modality in which most images are stored in analog fashion on videotape into one with most data stored digitally. This transition is accelerating today, fueled by several factors. First, there is widespread recognition of the value of digital storage of echocardiograms, including random access to studies as well as to images within a study, side-by side comparison with prior studies, easier quantification, and multiplication and remote transmission of images without degradation. Second, continuous improvement of the cost/performance ratio of modern computers makes routine digital echocardiography both feasible and affordable. Finally, the formulation and acceptance within the industry of the DICOM image formatting standard for echocardiography. The acceptance of this standard allows the echo-labs around the world to be free to choose individual echo-machines on the basis of their individual merits for their laboratories with the assurance that these machines will be able to communicate with each other by an internationally agreed upon standard. Advantages of digital echocardiography are overwhelming and there is little doubt that this approach will be essential for the proper utilization of this technique. The technology will undoubtedly continue to change. Those who are waiting for it to be perfected may be waiting for a long time. PMID- 11221586 TI - [Chlamydia pneumoniae and Helicobacter pylori infections in acute myocardial infarction]. AB - BACKGROUND: Increasing evidence suggests an acute or chronic linkage between infection and acute coronary syndromes. The aim of this study was to assess the frequency of Chlamydia pneumoniae (CP) and Helicobacter pylori (HP) antibodies in patients with angiographically defined acute myocardial infarction and in population controls. Case patients and controls were drawn from the same geographic area (city of Messina and its province). METHODS: Blood samples were collected in 206 incident cases of acute myocardial infarction presenting to the Coronary Care Unit (196 men, 10 women, mean age 58+/-7 years) in the period from March 1997 to June 1999. Case patients were selected if they were non-smokers, non-diabetic and if they had no history of hypertension. The control group consisted of 142 healthy subjects, without a known history of smoking, diabetes, and hypertension. Controls were matched to acute myocardial infarction patients for age, sex and socio-economic status. Commercial ELISA assay was used to measure IgG antibody to HP (positive titer > 8 IU/ml) and indirect immunofluorescence method was used to assess IgG antibody anti-CP (IgG titer > 1:64 was considered a marker of chronic infection). RESULTS: No significant difference was observed in the frequency of HP antibodies in acute myocardial infarction patients and in the control group (43.3 vs 41.5%, p = NS, odds ratio OR 1, 95% confidence interval-CI 0.7-1.6). On the contrary, CP titers were increased in 83% of acute myocardial infarction patients, and in 57% of control subjects (p < 0.001, OR 3.6, 95% CI 2.2-5.7). In acute myocardial infarction patients seropositivity for CP was associated with increased basal fibrinogen levels (539 vs 445 mg/dl). No correlation was found between seropositivity to CP and C-reactive protein, and with total or fractionated cholesterol and triglyceride concentrations. CONCLUSIONS: The present data indicate that, in our sample, acute myocardial infarction was associated with an increased frequency of CP seropositivity. The presence of CP antibodies was not associated with elevated levels of C-reactive protein. Our data support the need for controlled studies to investigate the role of these infective agents as a trigger of acute coronary syndromes. PMID- 11221587 TI - [Functional heart murmur and echocardiography: a solved problem?]. AB - BACKGROUND: Is it really vanished the need for echocardiography in the differential diagnosis of functional pediatric murmurs? METHODS: To this aim 260 children (132 males, 128 females; age range 1-84 months) were examined with auscultatory cardiac murmur. All children underwent a clinical and instrumental evaluation (ECG and echocardiography) from two pediatric cardiologists with independent assessment. RESULTS: Two hundred and ten patients (Group A) were evaluated clinically with functional murmur, 45 patients (Group B) with pathological murmur, 5 patients (Group C) with uncertain pathology. ECG showed changes in 1 Group B patient. Echocardiography showed pathology in 15 Group A patients (6 patients with patent foramen ovale, 5 patients with interatrial defect, 2 patients with bicuspid aortic valve, 1 patient with mitral insufficiency, 1 patient with restrictive cardiomyopathy). Pathology was excluded in 3 Group B patients, and in 2 Group C patients. In our clinical analysis echocardiography showed sensitivity 75%, specificity 97%, positive predictive value 90%, and negative predictive value 92%. CONCLUSIONS: In our experience we suggest to perform echocardiographic examination in children with functional murmur for complete assessment. PMID- 11221588 TI - [Kissing-stent technique for the treatment of spontaneous coronary artery dissection]. AB - A 60-year-old woman referred to our hospital because of increasing dyspnea and angina. Her past history included an anterior myocardial infarction, associated with a large coronary dissection of the proximal left anterior descending coronary artery. The infarction resulted in a ventricular aneurysm which was treated with surgical excision without coronary revascularization. Coronary angiography showed a linear filling defect involving the left anterior descending coronary artery. Intracoronary ultrasound revealed a long intimal tear dividing the artery into two separated lumens. A kissing-stent technique was used to preserve the anatomical and functional integrity of the main vessel as well as of the diagonal branch. Two premounted stents were positioned covering the origin of both branches of the bifurcation. Simultaneous inflation of the two balloons created a metallic new-carina, 1 cm proximal to the bifurcation. Five months later the patient was readmitted with chest pain and repeat coronary angiography demonstrated a severe in-stent restenosis. Re-coronary angioplasty resulted in a good angiographic result. At 4 months from the last procedure there is no complaint of angina. PMID- 11221590 TI - [Guideline for the diagnosis and treatment of unstable angina. Update 2000]. PMID- 11221589 TI - [Myocardial revascularization may resolve arrhythmic warm-up in patients with implantable cardioverter-defibrillator: 2 case reports]. AB - Patients with ventricular arrhythmias and coronary artery disease may have a poor clinical outcome because of an increased risk of sudden cardiac death. In these patients therapeutic approaches include two main strategies: automatic implantable cardioverter-defibrillator (ICD) and antiarrhythmic drugs (when left ventricular function is preserved). Patients with arrhythmic warm-up sustained by ischemic attacks may be stabilized after percutaneous or surgical revascularization. We report the cases of 2 ICD patients, in whom the correction of myocardial ischemia was successful in preventing further ICD discharges. In the first patient with known coronary artery disease (previous acute myocardial infarction and left ventricular ejection fraction 30%) a sudden arrhythmic warm up was reported with 70 ICD discharges in 24 hours; the patient underwent coronary artery bypass surgery and only few isolated episodes of ventricular tachycardia were observed during the following 34 months. In the second patient with a history of dorsal acute myocardial infarction and two previous interventions of coronary artery bypass graft surgery, we observed a sudden and unexpected arrhythmic instabilization with several ICD discharges. After percutaneous transluminal angioplasty of a graft stenosis, the clinical situation was stabilized and no more ICD activations were observed during the follow-up. In selected patients arrhythmic warm-up can rely on an ischemic substrate, then a careful re-evaluation for ischemia is mandatory in order to resolve the situation. PMID- 11221591 TI - [Legal implications of medical guidelines. A Task Force of the European Society of Cardiology]. PMID- 11221592 TI - [Interactions between ACE-inhibitors and aspirin]. PMID- 11221593 TI - [Effects of CPAP ventilation on cardiovascular outcome in patients with chronic heart failure with or without Cheyne-Stokes periodic respiration during sleep]. PMID- 11221594 TI - [Prognostic significance of the electrophysiologic study in the identification of patients with ischemic cardiopathy in high risk of sudden death]. PMID- 11221595 TI - [Association of hostility and calcification of coronary arteries in young people]. PMID- 11221596 TI - [Ventricular hypertrophy and risk of sudden death in hypertrophic cardiomyopathy]. PMID- 11221598 TI - [The meeting of Dante and Virgil with Pier delle Vigne: an example of clinical experimentation]. PMID- 11221597 TI - [Treatment of patients with acute coronary syndrome in the United States with glycoprotein IIb/IIIa inhibitors. Data provided by the PURSUIT study]. PMID- 11221599 TI - [Percussion of the cardiac area, literature and history of medicine]. PMID- 11221600 TI - Dietary supplements: an advertising guide for industry. PMID- 11221601 TI - The facts about weight loss products and programs. PMID- 11221602 TI - Human CYP1B1 Leu432Val gene polymorphism: ethnic distribution in African Americans, Caucasians and Chinese; oestradiol hydroxylase activity; and distribution in prostate cancer cases and controls. AB - Cytochrome P4501B1 (CYP1B1) is involved in the activation of many carcinogens and in the metabolism of steroid hormones, including 17beta-oestradiol (E2) and testosterone. We report a significant difference in the allele frequencies of two point mutations in the coding region of the CYP1B1 gene among Caucasian (n = 189), African-American (n = 52) and Chinese (Linxian) (n = 109) populations. A (C to G) transversion at position 1666 in exon 3, which results in an amino acid substitution of Leu432 to Val, was present in African-Americans with an allele frequency for Va1432 of 0.75, in Caucasians of 0.43, and in Chinese of 0.17. A (C to T) transition at position 1719 in exon 3, with no amino acid change (Asp449), appeared to be closely linked with the Val432 variant. Results using human lung microsomal preparations from individuals with the CYP1B1Val/Val and CYP1B1Leu/Leu genotypes indicate that Val432 variant may be a high activity allele and thus may contribute to the interindividual differences in CYP1B1 activity. Because CYP1B1 is involved in hormone and carcinogen metabolism, and given the disparate rates of prostate cancer among ethnic groups, we also evaluated the association of the CYP1B1 Leu432Val polymorphism with prostate cancer risk in a pilot case-control study. Among Caucasians, 34% of men with cancer (n = 50) were homozygous for the Val432 polymorphism, while only 12% of matched control subjects (n = 50) had this genotype. These preliminary data indicate that genetic polymorphisms in CYP1B1 might play an important role in human prostate carcinogenesis. PMID- 11221603 TI - Hyperglycemic crises in patients with diabetes mellitus. PMID- 11221604 TI - A pain in the back. PMID- 11221605 TI - A pain in the back. PMID- 11221606 TI - A pain in the back. PMID- 11221607 TI - Ibuprofen versus indomethacin for closure of patent ductus arteriosus. PMID- 11221608 TI - Absence of cardiac toxicity of zidovudine in infants. PMID- 11221609 TI - Polymorphisms in the factor VII gene and the risk of myocardial infarction. PMID- 11221610 TI - Depression and suicide in patients treated with isotretinoin. PMID- 11221611 TI - Obtaining informed consent in Bangladesh. PMID- 11221612 TI - Improve survival with plasma exchange thrombotic thrombopenic purpura-hemolytic uremic syndrome. PMID- 11221613 TI - Defamatory article by Martin Walker. PMID- 11221614 TI - Multiple complex coronary plaques in patients with acute myocardial infarction. PMID- 11221615 TI - Multiple complex coronary plaques in patients with acute myocardial infarction. PMID- 11221616 TI - Zanamivir to prevent influenza. PMID- 11221617 TI - Zanamivir to prevent influenza. PMID- 11221618 TI - Treating opioid dependence. PMID- 11221619 TI - Treating opioid dependence. PMID- 11221620 TI - Obesity, hypertension, and renal cancer. PMID- 11221621 TI - Transplantation of a tissue-engineered pulmonary artery. PMID- 11221622 TI - A fatal complication of noninvasive ventilation. PMID- 11221623 TI - Legalized physician-assisted suicide in Oregon, 1998-2000. PMID- 11221624 TI - Asthma, corticosteroids, and growth. PMID- 11221625 TI - Asthma, corticosteroids, and growth. PMID- 11221626 TI - Psychological factors and coronary artery disease. PMID- 11221627 TI - Psychological factors and coronary artery disease. PMID- 11221628 TI - Psychological factors and coronary artery disease. PMID- 11221629 TI - Psychological factors and coronary artery disease. PMID- 11221630 TI - Idiopathic clubbing. PMID- 11221631 TI - AIDS among heterosexuals in surveillance reports. PMID- 11221632 TI - George L. Weid, M.D., D.Sc. (hon), F.I.A.C. A tribute on his 80th birthday. PMID- 11221633 TI - Heart attacks: 10 things you should know. PMID- 11221634 TI - Diagnostic dilemma. Emphysematous cystitis. PMID- 11221635 TI - Administration of heme arginate, but not hematin, caused anaphylactic shock. PMID- 11221636 TI - Hemolytic anemia after acetaminophen overdose in patient with glucose-6-phosphate dehydrogenase deficiency. PMID- 11221637 TI - Diagnosing osteoporosis in Japanese American women. PMID- 11221638 TI - Chronic fatigue syndrome symptoms common in patient with vasovagal syncope. PMID- 11221639 TI - Lousy diagnostics in the emergency room. PMID- 11221640 TI - Public knowledge, attitudes, and experiences with antibiotic use for acute bronchitis. PMID- 11221641 TI - Apparent digestibility and proteic quality of the basic diet of Rio de Janeiro State complemented with multimixture. AB - Some factors in food can influence the protein digestibility positively or negatively. The protein quality is related to the protein synthesis capacity, growth, maintenance, reproduction and reconstitution of an organism. This work aims to determine the apparent digestibility coefficient and the protein quality of the standard basic diet of Rio de Janeiro State (HERJ), complemented with 2% of the multimixture (HERJ + MM), during rats' gestation and lactation periods. The results indicated a lower apparent digestibility coefficient (P < 0.05) during the gestation and lactation periods in HERJ diets (82.4% +/- 0.55; 80.64% +/- 1.7) and HERJ + MM (80.9% +/- 3.28; 81.7% +/- 1.2), in comparison to the casein diet (91.8% +/- 0.6; 93.9% +/- 0.4). There was no significant difference (P < 0.05) between HERJ diet (2.75 +/- 0.14) and HERJ + MM diet (2.53 +/- 0.18). However, the casein diet has showed a higher lactation value (3.27 +/- 0.3) in comparison with the two above mentioned groups. Therefore the use of the multimixture at 2% level neither impairs the apparent digestibility coefficient nor does it change the protein quality of the standard diet of Rio de Janeiro State. PMID- 11221642 TI - [Cloverleaf skull syndrome]. PMID- 11221644 TI - The 5th Asia-Pacific Congress on Animal, Plant and Microbial Toxins. October 12 15, 1999. Abstracts. PMID- 11221643 TI - [Approach to the border area--chronic coughs]. PMID- 11221645 TI - Bibliography of toxinology. PMID- 11221647 TI - Proceedings of the 8th International Conference on Intelligent Systems for Molecular Biology (ISMB 2000). San Diego, California, USA. August 19-23, 2000. PMID- 11221646 TI - Selected titles. PMID- 11221648 TI - Birth, The Beginning of Developmental Freedom. Jubilaeum Congress. Jerusalem, Assisi, Rome, September 2000. Abstracts. PMID- 11221649 TI - 18th International Congress of Biochemistry and Molecular Biology. 16-20 July 2000, Birmingham, United Kingdom. Abstracts. PMID- 11221650 TI - Second International Conference on Signal Transduction, Croatia May 2000. PMID- 11221651 TI - The 10th International Conference on Oral Iron Chelators in the treatment of beta thalassemia and other diseases and biomed meeting. AB - Development of oral iron (Fe) chelation therapy remains an important goal for the treatment of Fe-overload disease and perhaps other conditions. For many years, the major problem with Fe chelation therapy has been that the drug in clinical use. desferrioxamine (DFO), requires long sc. infusions (12-24 h day, 5-6 days per week). In addition, DFO is not orally effective, is highly expensive and does not easily permeate cell membranes to bind intracellular Fe pools. Obviously, the development of an orally effective and economical drug is vital. The recent 10th International Conference on Oral Iron Chelators (ICOC) discussed the latest findings in this challenging field. The conference was particularly focused to discuss recent investigations with the orally effective chelator, deferiprone (also) known as Li, DMHP or 1, 2-dimethylhydroxypyridone). PMID- 11221652 TI - A questionable diagnosis: thrombosis of the right common iliac vein. PMID- 11221653 TI - Aboriginal dance. PMID- 11221654 TI - Oral aspirin in post-operative pain: a quantitative, systematic review. Edwards et al.,PAIN 81 (1999) 289-297. PMID- 11221656 TI - The important time parameter is missing. Comment on Sindrup and Jensen, PAIN 83 (1999) 389-400. PMID- 11221655 TI - Neural toxicity of ketamine and othe NMDA antagonists. PMID- 11221657 TI - A unique method for oral administration of medications to infants. PMID- 11221659 TI - Postoperative neurologic deficit despite normal cerebral oximetry during carotid endarterectomy. PMID- 11221658 TI - Ineffectiveness of propofol on intraoperative seizure activity in a patient with medial temporal lobe epilepsy. PMID- 11221660 TI - Lamotrigine in refractory cancer pain. A case report. PMID- 11221661 TI - Intubation problems due to fiberoptic bronchoscope defect. PMID- 11221662 TI - Single point mutations in either gene encoding the subunits of the heterooctameric yeast phosphofructokinase abolish allosteric inhibition by ATP. AB - Yeast phosphofructokinase is a heterooctameric enzyme subject to a complex allosteric regulation. A mutation in the PFK1 gene, encoding the larger subunits, rendering the enzyme insensitive to allosteric inhibition by ATP was found to be caused by an exchange of proline 728 for a leucine residue. By in vitro mutagenesis, we introduced this mutation in either PFK1 or PFK2 and found that the exchange in either subunit drastically reduced the sensitivity of the holoenzyme to ATP inhibition. This was accompanied by a lack of allosteric activation by AMP, fructose 2,6-bisphosphate, or ammonium and an increased resistance to heat inactivation. Yeast cells carrying either one mutation or both in conjunction did not display a strong phenotype when grown on fermentable carbon sources and did not show any significant changes in intermediary metabolites. Growth on non-fermentable carbon sources was clearly impaired. The strain carrying both mutant alleles was more sensitive to Congo Red than the wild type strain or the single mutants indicating differences in cell wall composition. In addition, we found single pfk null mutants to be less viable than wild type at different storage temperatures and a pfk2 null mutant to be temperature-sensitive for growth at 37 degrees C. The latter mutant was shown to be respiration-dependent for growth on glucose. PMID- 11221664 TI - Headache World 2000. London, United Kingdom, 3-7 September 2000. Abstracts. PMID- 11221663 TI - A joint endeavor of the American Academy of Nursing and the American Nurses Foundation, established in 1998. PMID- 11221665 TI - The accident. PMID- 11221666 TI - On the death of my father. PMID- 11221667 TI - On the death of my father. PMID- 11221668 TI - Proceedings of the 41st Congress of The International Psychoanalytical Association. Santiago, Chile, 1999. PMID- 11221669 TI - Addressing issues for early detection and screening in ethnic populations. 1997. PMID- 11221670 TI - Turning point: environmental health in Brazil. PMID- 11221671 TI - Environmental and public health: pulling the pieces together. PMID- 11221672 TI - Fresh ideas for food safety. PMID- 11221673 TI - Smoke-filled rooms. ETS causes menstrual pain. PMID- 11221674 TI - A clearer look at PM(10): multiday assessment provides better data. PMID- 11221676 TI - Addiction treatment works how research helps to overcome ideology. PMID- 11221675 TI - Childhood tooth decay: is it linked to lead? PMID- 11221677 TI - Imino sugar therapy for type 1 Gaucher disease. PMID- 11221679 TI - Centers for Disease Control says arenavirus spread unlikely. PMID- 11221678 TI - How proapoptotic proteins can escape from mitochondria? PMID- 11221680 TI - Misuse and resistance to antibacterial drug products addressed in labeling. PMID- 11221681 TI - HLA-G and HLA-E: fundamental and pathophysiological aspects. PMID- 11221682 TI - Innate immunity: a primitive system in humans. PMID- 11221683 TI - Immunoregulation in parasitic infection: insights for therapeutic intervention. PMID- 11221684 TI - Perforin deficiency: fighting unarmed? PMID- 11221685 TI - On the pathogenesis of perforin defects and related immunodeficiencies. PMID- 11221687 TI - Bibliography of toxinology. PMID- 11221686 TI - Incidence of cancer among commercial airline pilots. PMID- 11221690 TI - Should tuberculosis prophylaxis be given to chronically dialyzed patients? PMID- 11221689 TI - [Genetic study of multiple sclerosis]. PMID- 11221688 TI - Discovered by Carlos Chagas in 1909 in Brazil, America trypanosomiasis has scourged vast area of the country. PMID- 11221692 TI - [Circular anopexia: a new approach to surgical treatment of hemorrhoid disease]. PMID- 11221691 TI - [Risks incurred by the first intravenous drug injection]. AB - AIMS: The objectives of the study were to describe the circumstances surrounding the initiation of intravenous drug use, the role of the introducer and to evaluate intravenous drug users risk behaviors at the first injection of drug. DESIGN: In 1997, we conducted a cross-sectional survey using a structured questionnaire concerning the initiation process into intravenous drug abuse. IDUs were interviewed in four treatment drug abuse and psychosocial centers in Paris and in one prison. PARTICIPANTS: Of the 152 consecutive IDUs interviewed, 143 completed the questionnaire, 83 were male. FINDINGS: The mean age at first opiate use and at first injection were 19 years (SD: 4.3) and 20 years (SD: 4.3). At first injection, heroin was the main used drug (91%), the subject was with others persons (91%), asked himself for injection (70%) albeit had not planned this injection (40%). The subject injected at a friend's home (31%). The introducer was an IDU (93%), mean age 23.4 (SD: 5.2). He or she was a friend (61%) or a sexual partner (14%). The preparation of the first injection and the injection were made by the introducer in 72 % and 74 % of cases. The injecting equipment had been borrowed (22%) from an IDU whose HIV status and HCV status were unknown in 83 % and 85 % of cases. CONCLUSION: Our study shows novel results about the first injection, they are of prime importance for harm reduction. The introducer plays a major role in preventing risk-behavior at the first injection and for education about safe injecting practices. PMID- 11221693 TI - [What is the importance of liver fibrosis in overweight patients?]. PMID- 11221694 TI - Proceedings of the 9th International Symposium on New Frontiers of Neurochemistry and Biophysics in the Acute and Chronic Neurological Diseases. Marin, Slovak Republic, 16-19 August 1999. PMID- 11221695 TI - American Board of Prosthodontics. PMID- 11221697 TI - [Poliomyelitis]. PMID- 11221696 TI - [Rift Valley fever]. PMID- 11221698 TI - [Lymphatic filariasis]. PMID- 11221699 TI - [Concerning tuberculosis]. PMID- 11221701 TI - [A third of deaths caused by malaria in Africa are imputable to conflicts and natural disasters]. PMID- 11221700 TI - [Progress of medicine threatened by drug resistance]. PMID- 11221702 TI - [Fight against malaria and the fiscal matters: appeal to African countries]. PMID- 11221703 TI - [In Sydney the athletes suffering from malaria appeal for reinforcement of action against it]. PMID- 11221704 TI - Urine stone formation during treatment with zonisamide. PMID- 11221705 TI - Periventricular leukomalacia and tumor necrosis factor. PMID- 11221706 TI - Arthritis. PMID- 11221707 TI - Cardiovascular disease. PMID- 11221708 TI - Cancer multidrug resistance. PMID- 11221709 TI - Malaria. PMID- 11221710 TI - Antibacterial and antifungal drug discovery. PMID- 11221711 TI - Progress against HIV. PMID- 11221712 TI - Bioinformatics. PMID- 11221713 TI - Data mining. PMID- 11221714 TI - Signal transduction as a drug-discovery platform. PMID- 11221715 TI - Pharmacogenomics. PMID- 11221716 TI - Biochips. PMID- 11221717 TI - Proteomics. PMID- 11221718 TI - Lead validation platforms. PMID- 11221719 TI - Combinatorial chemistry. PMID- 11221721 TI - Agricultural biotechnology. PMID- 11221720 TI - Tissue engineering. PMID- 11221722 TI - Autoimmune disease. PMID- 11221723 TI - Heading towards the light. PMID- 11221724 TI - Prevalence of the vanB2 gene cluster in vanB glycopeptide-resistant enterococci in the United Kingdom and the Republic of Ireland and its association with a Tn5382-like element. PMID- 11221725 TI - Need for additional, specific information in studies with echinacea. PMID- 11221726 TI - Macrolide resistance in Campylobacter coli of animal origin in Denmark. PMID- 11221727 TI - Study patients and routine practice patients. PMID- 11221728 TI - Long-term anticoagulation therapy? PMID- 11221729 TI - An unusual experience with posterior pericardiotomy. PMID- 11221731 TI - Aortic root replacement with coronary button reimplantation. PMID- 11221730 TI - Neuroprotective effects of pre-treatment with systemic steroids in a neonatal piglet model of cardiopulmonary bypass with deep hypothermic circulatory arrest. PMID- 11221732 TI - Transhiatal simultaneous resection of a benign mediastinal pseudotumor and hiatal hernia repair. PMID- 11221733 TI - Radicality of thoracoscopic thymectomy--an anatomical study. PMID- 11221734 TI - Early and long-term complaints following video-assisted thoracoscopic surgery: evaluation in 173 patients. PMID- 11221736 TI - Is Brazil entering a new age? PMID- 11221735 TI - Mitral annuloplasty with a suture technique. PMID- 11221737 TI - Letter from the guest editor. Colorectal carcinoma. PMID- 11221738 TI - [La Revue Neurologique has received the following correspondence]. PMID- 11221739 TI - Interdisciplinary research: what, why and how. PMID- 11221740 TI - Comments on patterns of academic achievement among early treated patients with phenylketonuria. PMID- 11221741 TI - Comments on in vivo proton magnetic resonance spectroscopy in phenylketonuria. PMID- 11221742 TI - Comments on diet and compliance in phenylketonuria. PMID- 11221743 TI - Comments on final intelligence in late treated patients with phenylketonuria. PMID- 11221744 TI - Comments on the International Collaborative Study of Maternal Phenylketonuria: status report 1998. PMID- 11221745 TI - Phenylketonuria: evidence-based clinical practice. Summary of the roundtable discussion. PMID- 11221746 TI - The effect of a phenylalanine-restricted diet on phenylketonuria. PMID- 11221747 TI - Comments on neuropsychological approaches to treatment policy issues in phenylketonuria. PMID- 11221748 TI - Comments on behavior in early treated phenylketonuria. PMID- 11221749 TI - Basal ganglia, Parkinson's disease and levodopa therapy. Proceedings of a meeting. St Thomas, Virgin Islands, January 2000. PMID- 11221750 TI - Whatever it takes. PMID- 11221751 TI - Lab ventilation standard revisited. The user-friendly ANSI/AIHA Z9.5 Standard will affect every lab. American National Standards Institute/American Industrial Hygiene Association. PMID- 11221752 TI - Quiz case. Avascular necrosis of the metacarpal head III. PMID- 11221754 TI - The supersite - digital methadone. PMID- 11221753 TI - Reactivity to a 35% CO(2) challenge in healthy first-degree relatives of patients with panic disorder. PMID- 11221755 TI - A case of chronic inflammatory demyelinating polyneuropathy with antigalactocerebroside antibody. PMID- 11221756 TI - Disseminating information about new therapies for Parkinson's disease: misunderstanding or misconduct? PMID- 11221757 TI - [R. Degos, E. Rivalier, P. Lefort: "Griseofulvin". 1960]. PMID- 11221758 TI - [A. Bazex, A. Dupre: "Prurigo strophulus, a parasitic syndrome due to insect bites. Etiological, clinical and development modalities". 1965]. PMID- 11221759 TI - [G. Orth, D. Dompmartin, P. Agache, M. Faure, O. Croissant: "The plurality of human papillomaviruses". 1978]. PMID- 11221760 TI - [D. Wallach, C. Foldes, F. Cottenot: "Subcorneal pustulosis, superficial acantholysis and monoclonal IgA". 1982]. PMID- 11221762 TI - [13 decades of history of the Annales and of Dermatology]. PMID- 11221761 TI - [M. Bagot, N. Terki, S. Bacha, D. Moyse, C. Suck, J. Revuz: "Per os desensitization in nickel contact eczema: a double-blind placebo-controlled clinico-biological study. 1999]. PMID- 11221763 TI - [Joseph Rollet: "Inoculated syphillis". 1873-1874]. PMID- 11221764 TI - [Alfred Fournier: "Syphilitic locomotor ataxia". 1882]. PMID- 11221765 TI - [Jean Darier: "Papillary and pigmentary dystrophy. Acanthosis nigricans". 1895]. PMID- 11221766 TI - [C. Levaditi: "New means of microbial and serological diagnosis of syphilis". 1909]. PMID- 11221767 TI - [L.A. Longin: "Contribution to the study of so-called facts of congelation of feet". 1914-1915]. PMID- 11221768 TI - [Jean Darier: "The three planes of dermatological diagnosis". 1923]. PMID- 11221769 TI - [Jean Darier: "Historical considerations on the development of dermatology". 1936]. PMID- 11221770 TI - [James Marshall: "Penicillin treatment of syphilis". 1945]. PMID- 11221771 TI - Intragraft thrombus: an early CT finding in aortic graft infection. PMID- 11221772 TI - Curricular and extracurricular activities of medical students during war, Zagreb University School of Medicine, 1991-1995. AB - War, as a major human disaster, affects many aspects of life, including medical education. This report describes curricular and extracurricular activities of the students at the Zagreb University School of Medicine during the wars in Croatia and neighboring Bosnia and Herzegovina. Although condensed versions of the curricula were prepared in case of a major breakdown in civilian life, the school maintained the continuity and quality of its curriculum throughout the war. Students engaged in extracurricular activities related to medical aspects of the war, including organization of resuscitation and first aid courses, collecting medical documentation on war victims, humanitarian help to refugees, and peace promoting activities. Some students joined mobile surgical teams on the battlefronts. After army service, most of them returned to the school and successfully continued with their studies. The school also accepted guest students from other new states emerged from former Yugoslavia. The authors found that the students' engagement in extracurricular activities related to medicine was enormously beneficial both to the psychological well-being of the students and to the region's peace-building efforts. PMID- 11221773 TI - Radiosurgery for trigeminal neuralgia. PMID- 11221774 TI - Timeline: endovascular therapy for arteriovenous malformations. PMID- 11221775 TI - Society merger? PMID- 11221776 TI - Evolving cell death in the virus-infected nervous system. PMID- 11221777 TI - First dose hypotension after myocardial infarction. PMID- 11221778 TI - Persistent left superior vena cava in Holt-Oram syndrome. PMID- 11221779 TI - Are physicians recommending coronary angiographies more than necessary in atrial fibrillation. PMID- 11221780 TI - Serotonin syndrome risk with antiobesity drug. PMID- 11221781 TI - Partnering with industry: fences and good neighbors. PMID- 11221782 TI - History and evolution of computerized electroencephalography. PMID- 11221783 TI - Fundamental scientific factors in electrical stimulation of the nervous system. PMID- 11221785 TI - Motor nerve conduction studies: measurement principles and interpretation of findings. AB - Motor nerve conduction studies are reviewed. The principles of electrode placement, stimulus intensity, algorithms for measurement of parameters, causes of variability, reference values, and reporting are discussed. A rigorous standardization of methods has several advantages. The sensitivity of each method is increased without loss of specificity. In addition, reference values obtained in one laboratory can be used in other laboratories as well. Pathophysiological interpretation of findings in different types of neuropathies is also presented. PMID- 11221784 TI - Assessment of intraspinal and intracranial conduction by P30 and P39 tibial nerve somatosensory evoked potentials in cervical cord, brainstem, and hemispheric lesions. AB - In routine recordings of tibial nerve somatosensory evoked potentials (SEPs), a global central conduction time is evaluated by measuring the interval between the segmental spinal N22 potential, recorded in the lumbar region, and the cortical P39 potential. In this study, we tested the reliability of the scalp far-field P30 potential, which originates in the vicinity of the cervico-medullary junction, in order to evaluate separately intraspinal and intracranial conduction in normal subjects and patients with cervical cord and intracranial lesions. P30 and cortical P39 potentials were studied in 23 healthy subjects and in 70 patients with cervical cord (n = 47), brainstem (n = 11) or hemispheric lesions (n = 12) selected on the basis of neuroimaging--computed tomography (CT) or magnetic resonance (MR)--findings. Median nerve SEPs were also recorded in all patients. Of the several montages tested to obtain the P30 potential, the Fpz-Cv6 derivation gave the highest signal-to-noise ratio; it permitted to obtain a P30 potential that peaked at 29.2 +/- 1.6 ms in all normal subjects. P30 abnormalities were observed only in patients with cervical or cervico-medullary lesions; these were associated with a normal P39 in only two of 33 abnormal recordings. Conversely, P30 was consistently normal in lesions situated above the cervico-medullary junction whether associated with normal, delayed, or reduced P39. P30 abnormalities were subclinical in 42% of abnormal recordings. All patients with normal tibial and median nerve SEPs on both sides had normal touch, joint, and vibration sensation in the four limbs. There was a strong correlation between tibial nerve P30 and median nerve P14 data in the whole series of patients; both potentials behaved similarly in all cases of intracranial supramedullary lesions. Combined abnormalities of P30 and P39 potentials thus indicate that conduction is impaired at the spinal level and proved to be particularly informative for detecting spinal cord dysfunction in patients with neuroimaging evidence of a narrowed cervical canal. Recording of abnormal N13, P14, or P30 potentials provided evidence of a cervical cord dysfunction in 66% of patients who had a suspected spondylotic myelopathy. Recording of tibial nerve P30 potential has proven to give reliable and useful information when a separate assessment of intraspinal and intracranial somatosensory conduction is needed; it merits inclusion, as does the upper limb N13 potential, in the evaluation of patients whose MR image indicates cervical canal narrowing. PMID- 11221786 TI - Temporal intermittent rhythmic delta activity in electroencephalograms. AB - Temporal intermittent rhythmic delta activity (TIRDA) has been reported to be highly specific for diagnosing complex partial epilepsy. Of 12,198 electroencephalographic (EEG) recordings performed at the Mayo Clinic between May 1, 1990 and May 1, 1991, 33 records from 27 patients (18 women and nine men; mean age, 41.5 years; range, 13-82 years) showed TIRDA. Clinical seizures were diagnosed in all patients, and complex partial epilepsy was well documented in 23. In a control group of 100 patients without TIRDA and matched for age and sex, generalized seizures were diagnosed in 25 and partial seizures in 15. Differences between TIRDA and control groups were highly statistically significant. Focal temporal sharp waves or spikes occurred in 23 patients with EEG recordings that contained TIRDA; three of these patients also exhibited generalized atypical spike-and-wave discharges. Four patients had TIRDA but no other epileptiform activity, although earlier EEGs of three of these patients contained spikes or sharp waves. These findings confirm earlier work, and we conclude that TIRDA represents an important epileptogenic abnormality. PMID- 11221787 TI - Quantitative analysis of the electroencephalogram in the intracarotid amobarbital procedure: II. Coherence analysis. AB - Thirty-seven subjects underwent bilateral internal carotid artery injections of amobarbital before surgery for intractable epilepsy. The electroencephalograms (EEG) of these patients were continuously monitored during these 74 procedures and were later subjected to quantitative analysis. Analysis of interhemispheric coherence in the delta, theta, alpha, and beta 1 bands was performed. Prominent changes occurred in interhemispheric coherence, which showed a precipitous drop in the first 2 min after amobarbital injection, followed by a gradual return to near baseline levels. These results suggest that interhemispheric relationships are significantly disrupted by intracarotid amobarbital injection. PMID- 11221788 TI - Middle-latency somatosensory evoked potentials after stimulation of the radial and median nerves: component structure and scalp topography. AB - Somatosensory evoked potentials (SEPs) after radial nerve stimulation are studied less frequently than those after median nerve stimulation. Therefore, little is known about their component structure and scalp topography. We investigated radial nerve SEPs after electrical stimulation at the left wrist. For comparison, the median nerve was also stimulated at the wrist. SEPs were recorded with 15 scalp electrodes (bandpass 0.5-200 Hz) in 27 healthy subjects. The waveform of the radial nerve SEP at a contralateral parietal lead was comparable to that of the median nerve SEP, consisting of P14, N20, P30, and N60. In spite of comparable stimulus intensities, SEP amplitudes were smaller after radial than after median nerve stimulation. Significant latency differences were found only for N20 (earlier for median nerve) and P30 (earlier for radial nerve). The duration of the primary complex N20-P30 thus was significantly shorter for the radial nerve. Whereas N20 and P30 were present with either earlobe or frontal reference, N60 had a prerolandic maximum and was best recorded with a bipolar transverse derivation. In addition, another middle-latency negativity (N110) was found near the secondary somatosensory cortex, which had previously been described only for radial nerve stimulation. In standard SEP derivations, the N110 is riding on the ascending limb of the vertex negativity. It could best be recorded in low temporal leads versus a midline reference. The scalp topographies of P30, N60, and N110 were similar for radial and median nerve stimulation. PMID- 11221789 TI - Ambulatory cassette polysomnography: findings from a large cohort of drug-free insomnia patients. AB - Technology for conducting ambulatory polysomnography (APSG) has been available for more than a decade, but relatively few studies have used this technology to study the sleep of subjects in their usual home sleeping environments. Herein we suggest the usefulness of this technology for the study of normal sleepers and insomniacs, and we report our APSG findings with a large cohort (n = 117) of drug free insomnia outpatients. All patients completed a sleep-history questionnaire, a clinical interview with a sleep-disorders clinician, and one night of APSG in their homes. Most sleep parameters derived were consistent with previously reported laboratory PSG findings for insomniacs, except that values of rapid-eye movement sleep latencies were generally shorter than typically found in laboratory studies. Moreover, results showed that APSG served to differentiate major age groups and diagnostic subtypes within our larger sample, and patient tolerance for APSG was within acceptable limits. We conclude that APSG is a useful technique for evaluating insomnia complaints. PMID- 11221790 TI - XIII Meeting on ADP-Ribosylation Processes. Torino, Italy, October 8-9, 2000. Abstracts. PMID- 11221791 TI - Strength through unity: why become a mentor for podiatric medicine? PMID- 11221793 TI - Solar-powered device decontaminates human immunodeficiency virus (HIV)-infected breast milk. PMID- 11221792 TI - Re: Wight et al. Aging, serum estradiol levels, and pregnancy differentially affect vascular reactivity of the rat uterine artery. J Soc Gynecol Investig 2000;7:1060-113. PMID- 11221794 TI - [Concerning "Arthroscopic debridement of full-thickness tears of the rotator cuff: a retrospective multicenter study of 283 cases with 3-year follow-up"]. PMID- 11221795 TI - [Concerning: "Effectiveness of postoperative drainage after bipolar sealed endoprosthetic arthroplasty for femur neck fracture. Results of a prospective randomized study of 86 cases"]. PMID- 11221796 TI - [Concerning "Aggressive osteoblastoma of the carpal scaphoid bone"]. PMID- 11221797 TI - Impact of the new WHO classification and diagnostic criteria. AB - The World Health Organisation (WHO) [1] consultation group and the American Diabetes Association (ADA) [2] have recently published revised criteria for the classification and diagnosis of diabetes. If widely implemented, these recommendations, together with earlier and improved treatment, could have a profound impact on the morbidity and mortality associated with the disease. The changes in classification stem from an increased knowledge of the aetiology and pathogenesis of diabetes, which signals the move away from a classification system based on pharmacological dependency towards one that is based on the underlying causes of the disease. PMID- 11221798 TI - The role of blood glucose-lowering drugs in the light of the UKPDS. United Kingdom Prospective Diabetes Study. PMID- 11221800 TI - Atherothrombosis in diabetes--its evolution and management. PMID- 11221799 TI - Cardiovascular risk in type 2 diabetes. PMID- 11221801 TI - The natural history of diabetes-related complications: the UKPDS experience. United Kingdom Prospective Diabetes Study. PMID- 11221802 TI - Absence of echovirus sequences in brain and spinal cord of amyotrophic lateral sclerosis patients. AB - The role of enteroviruses in pathogenesis of amyotrophic lateral sclerosis (ALS) is controversial. A recent study, based on reverse transcription-polymerase chain reaction (RT-PCR) analysis of spinal cord, reported identification of a novel echovirus in 15 of 17 French subjects with ALS and only 1 of 29 subjects with other neurologic diseases. We established a real-time RT-PCR method based on this novel echovirus sequence and used this method and that previously employed for analysis of the French subjects to determine the prevalence of echoviral sequences in spinal cord and motor cortex of sporadic ALS subjects from the United States. No echoviral sequences were found in 20 spinal cord and 10 motor cortex samples from autopsy-confirmed cases of ALS or 13 spinal cord and 5 motor cortex samples from subjects with no motor neuron disease. PMID- 11221803 TI - The role of the oncology nurse in cancer gentic counseling. Oncology Nursing Society. PMID- 11221804 TI - Cancer predisposition genetic testing and risk assessment counseling. Oncology Nursing Society. PMID- 11221805 TI - Characterization of microsatellite loci in the eastern oyster, Crassostrea virginica. PMID- 11221806 TI - [Analytical comment on the article: "Iridology: not useful and potentially harmful." E. Ernst, (Edin)--Arch Ophthalmol. 2000, 118: 120-1021]. PMID- 11221807 TI - UKPDS and beyond: into the next millennium. United Kingdom Prospective Diabetes Study. PMID- 11221808 TI - Serum leptin levels are not influenced by physical training in type 2 diabetes mellitus patients. AB - AIM: To investigate the effect of physical training on leptin levels in elderly, obese patients with type 2 diabetes mellitus. METHODS: Twenty men and 38 women with type 2 diabetes mellitus with a body mass index (BMI) of > 25 kg/m2 participated in a prospective randomized study. Patients were either on oral glucose lowering drugs (n = 39) or insulin therapy (n = 19). Physical training consisted of a guided, standardized, 6-week training programme performed in the hospital on a cyclo ergometer followed by a 6-week period of guided training at home and ended in a 12-week period of training at home without supervision. Clinical data and laboratory samples including fasting insulin and leptin levels and maximal aerobic capacity were assessed at the start of the study and at 6 and 26 weeks thereafter. RESULTS: Physical training resulted in significantly positive changes in maximal aerobic capacity (VO2max) and maximum work load. No effects of physical training on serum leptin levels and insulin concentrations were detected. Leptin levels were strongly correlated with body mass index (r = 0.63), body fat content (r = 0.61), and fasting insulin concentrations (r = 0.38). Women had threefold higher leptin levels than men. No differences in leptin levels between patients on insulin therapy and patients on oral glucose lowering drugs were found. CONCLUSIONS: No effect of physical training on leptin levels was detectable in elderly, obese type 2 diabetes mellitus patients. PMID- 11221810 TI - Nerve regeneration in diabetic neuropathy. PMID- 11221809 TI - Acarbose vs. bedtime NPH insulin in the treatment of secondary failures to sulphonylurea-metformin therapy in type 2 diabetes mellitus. AB - OBJECTIVE: To evaluate the efficacy of acarbose in the treatment of secondary failures to sulphonylurea-metformin therapy, its comparison against bedtime NPH insulin, and to measure the changes in postprandial metabolism resulting from both treatments. METHODS: One hundred type 2 diabetic patients in a secondary failure were included. The study begun with a run-in diet period of 6 weeks, in which an isocaloric diet was prescribed. Only subjects who continued hyperglycaemic were randomly assigned to placebo and acarbose (n = 17) or bedtime NPH insulin (n = 12). Acarbose (300 mg/day) or placebo were administered using a randomized, double blind, crossover design. Treatment periods of 3 months were separated by a 3-week washout period. Insulin was administered during 3 months. At the beginning and the end of each treatment period, an i.v. glucose tolerance test and a meal test were performed. Safety tests were done every 4 weeks. RESULTS: Acarbose resulted in a small but significant improvement in fasting plasma glucose (13.5 +/- 2.4 vs. 11.3 +/- 3.9 mmol/l, p = 0.05), HbA1c (11.1 +/- 3.4 vs. 10.3 +/- 2.5%, P = 0.3) and in a decreased plasma glucose during the meal test. Bedtime insulin significantly decreased fasting plasma glucose (13.1 +/- 2.9 vs. 8.2 +/- 2.3 mmol/l, p < 0.01), HbA1c (11.7 +/- 2.9 vs. 9.4 +/- 2.7%, p < 0.01) and plasma cholesterol. No change in insulin secretion resulted from insulin and acarbose treatment. CONCLUSIONS: Acarbose decreases blood glucose in secondary failure to sulphonylurea-metformin therapy; however, the decrease is not enough to reach the desired metabolic control. Bedtime NPH insulin is, by far, a more effective alternative. PMID- 11221811 TI - Cilostazol, a phosphodiesterase inhibitor, improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty Rat, a model of spontaneous NIDDM. AB - AIM: Angiotensin converting enzyme inhibitors and alpha1-adrenergic blockers improve insulin sensitivity, the mechanism of which was considered, at least in part, to be due to the increased blood flow to muscle. The present study aimed to clarify whether cilostazol, a phosphodiesterase inhibitor, improves insulin sensitivity in a model of spontaneous non-insulin dependent diabetes mellitus (NIDDM), Otsuka Long-Evans Tokushima Fatty (OLETF) rat. METHODS: OLETF rats were divided into the two groups at the age of 16 weeks: the cilostazol-supplemented group (cilostazol 40 mg/kg/day) and the normal-diet group. As a non-diabetic control, we used Long-Evans-Tokushima-Otsuka rats (non-diabetic rats). Oral glucose tolerance test and hyperinsulinemic euglycemic clamp was performed at the ages of 23 and 25 weeks, respectively. Serum levels of lipids and leptin were measured. RESULTS: Body weight and abdominal fat was increased in OLETF rats but cilostazol supplementation did not alter them. Insulin sensitivity, as measured by the hyperinsulinemic euglycemic clamp technique, was significantly decreased in OLETF rats (glucose infusion rate: 73.5 +/- 10.0 vs. 41.5 +/- 9.8 micromol/min/kg body weight, p < 0.01). Cilostazol supplementation improved insulin sensitivity partially but significantly 51.0 +/- 5.7 micromol/min/kg body weight, p < 0.05) in OLETF rats at 25 weeks of age, although it did not decrease serum levels of glucose, lipids or leptin. However, this effect was not observed in non-diabetic rats. CONCLUSION: Cilostazol, which is used in diabetic patients for the treatment of obstructive disease of artery, is expected to have a beneficial effect on insulin sensitivity in NIDDM. PMID- 11221813 TI - Lowering of circulating insulin and leptin is closely associated following weight reduction after vertical banded gastroplasty in obese women. AB - AIM: To explore whether the lowering of insulin relates to changes in leptin following weight reduction after vertical banded gastroplasty (VBG) in seven grossly obese women (BMI 45.9 +/- 1.5 kg/m2). RESULTS: At 6-24 months after VBG, BMI was reduced to 31.3 +/- 0.9 kg/m2 (p < 0.018), leptin from 43 +/- 9 to 12 +/- 2 ng/ml (p < 0.018) and insulin from 172 +/- 19 to 71 +/- 2 pmol/l (p=0.018). The reduction in leptin correlated to the reduction in insulin (r = 0.94, p = 0.002) but not to that of BMI (r = 0.05, NS). CONCLUSION: Reduction in insulin seems more important for reduction in leptin than lowering of BMI, suggesting a close association between leptin and insulin in obese subjects. PMID- 11221812 TI - Clenbuterol stimulates neurotrophic support in streptozotocin-diabetic rats. AB - BACKGROUND: The diabetic neuropathies are characterized by axonal degeneration of peripheral nerves. The commonest variant of this condition is distal symmetrical polyneuropathy, in which the principal presenting features can be explained by impaired neurotrophic support of sensory neurones. AIMS: The aims of these experiments were to determine whether deficits in nerve growth factor (NGF) content and the products of its target genes (substance P and calcitonin-gene related peptide; CGRP) in the sciatic nerve of streptozotocin-induced rats could be prevented using clenbuterol, which has been demonstrated to induce NGF synthesis in vitro. RESULTS: Diabetes of 8 weeks duration produced a reduction in measurable sciatic nerve NGF-like immunoreactivity (NGF-LI) content of 53% (p < 0.01). This was accompanied by depletion of substance P (of 43%; p < 0.01) and CGRP (of 45%; p < 0.01). Treatment with clenbuterol (30 microg/kg, 100 microg/kg and 300 microg/kg; daily subcutaneous injection) significantly increased the NGF LI and neuropeptide content of the sciatic nerve, with 30 microg/kg of clenbuterol normalising the levels in diabetic animals. The alterations in steady state sciatic nerve NGF-LI were proportionally related to the amount of NGF-LI delivered to the primary afferent neurones via retrograde transport. Thus, there was a significant reduction in accumulation of NGF-LI distal to a 12-h ligature in diabetic untreated rats (p < 0.01), which was normalized by clenbuterol (30 microg/kg; p < 0.05). Treatment of control or diabetic rats with clenbuterol did not affect the local production of NGF-LI in the sciatic nerve adjacent to and triggered by an occluding ligature. The change in NGF-LI content of neuronal tissue in the clenbuterol treated rats was a reflection of the capture of NGF derived from the peripheral targets of the sciatic nerve. The soleus and EDL muscles showed reductions in NGF-LI in untreated diabetic animals. Clenbuterol significantly (p < 0.05) increased NGF-LI in the soleus muscle. CONCLUSION: Clenbuterol could be a useful tool in alleviating the deficits in neurotrophin support in diabetes. PMID- 11221814 TI - Smoking habits and circulating leptin in postmenopausal non-obese women. AB - This study examined whether smoking habits affect the correlation between serum leptin levels and body mass index (BMI) in 101 postmenopausal Caucasian non-obese women, all aged 57-59years. Mean serum leptin level in the entire group was 19.8 +/- 12.3 ng/ml (mean +/- s.d.) and mean BMI was 25.3 +/- 3.5 kg/m2. These parameters correlated significantly to each other (r = 0.70, p < 0.001). Between those who have smoked regularly for more than 2 years (n = 26) and those who are ex-smokers or have never smoked (n = 75), serum leptin levels or BMI did not differ and the correlation between serum leptin and BMI was identical. This suggests that smoking habits do not influence circulating leptin in Caucasian postmenopausal non-obese women. PMID- 11221815 TI - Reflections on "a longitudinal study of the effects of graduate medical education on hospital operating costs". PMID- 11221816 TI - How would mental health parity affect the marginal price of care? AB - OBJECTIVE: To determine the impact of parity in mental health benefits on the marginal prices that consumers face for mental health treatment. DATA SOURCES/DATA COLLECTION: We used detailed information on health plan benefits for a nationally representative sample of the privately insured population under age 65 taken from the 1987 National Medical Expenditure Survey (Edwards and Berlin 1989). The survey was carefully aged and reweighted to represent 1995 population and coverage characteristics. STUDY DESIGN: We computed marginal out-of-pocket costs from the cost-sharing benefits described by policy booklets under current coverage and under parity for various mental health treatment expenditure levels using the MEDSIM health care microsimulation model developed by researchers at the Agency for Healthcare Research and Quality. Descriptive analyses and two limit Tobit regression models are used to examine how insurance generosity varies across individuals by demographic and socioeconomic characteristics. Our analyses are limited to a description of how parity would change the marginal incentives faced by consumers under their existing plan's cost-sharing arrangements for mental and physical health care. We do not attempt to simulate how parity might affect the level of benefits, including whether benefits are offered at all, or the level of managed care that affects the actual benefits that plan members receive. Rather, we focus only on the nominal benefits described in their policy booklets. PRINCIPAL FINDINGS: Our results show that as of 1995 parity coverage would substantially reduce the share of mental health expenditures that consumers would pay at the margin under their existing plan's cost-sharing provisions, with larger changes for outpatient care than for inpatient care. Because current mental health coverage generally becomes less generous as expenditures rise, while coverage for other medical care becomes more generous (due to stop-loss provisions), the difference in incentives between current mental health coverage and the assumed parity coverage widens as total expenditure grows. We also find that the impact of parity on marginal incentives would vary greatly across the privately insured population. CONCLUSIONS: Based on the large variation in the impact of parity on marginal incentives across the population under current plan cost-sharing arrangements, changes in the demand for mental health treatment will likely also vary across the population. PMID- 11221817 TI - Evaluating large and complex demonstrations: the CHAMPUS reform initiative experience. Civilian Health and Medical Program of the Uniformed Services. AB - OBJECTIVE: To examine the evaluation process for the CHAMPUS Reform Initiative (CRI) both to highlight issues that evaluators must consider when undertaking such projects and to provide policymakers with tools to better assess demonstration project evaluations. DATA SOURCES: The CRI evaluation. STUDY DESIGN: Case study. DATA COLLECTION: Review of CRI evaluation reports. PRINCIPAL FINDINGS: Although policymakers increasingly rely on the evaluations of demonstration projects to determine whether to extend the scope and funding of many public programs, the results of these evaluations are often difficult to assess. Despite its analytical sophistication, the CRI evaluation was no exception. The somewhat artificial time constraints imposed by policymakers made projection of the CRI's performance beyond the demonstration period particularly difficult. CONCLUSIONS: Much uncertainty generally remains even after well planned and well-executed evaluations of demonstration projects. PMID- 11221818 TI - Comparing mortality and time until death for medicare HMO and FFS beneficiaries. AB - OBJECTIVE: To compare adjusted mortality rates of TEFRA-risk HMO enrollees and disenrollees with rates of beneficiaries enrolled in the Medicare fee-for-service sector (FFS), and to compare the time until death for decedents in these three groups. DATA SOURCE: Data are from the 124 counties with the largest TEFRA-risk HMO enrollment using 1993-1994 Medicare Denominator files for beneficiaries enrolled in the FFS and TEFRA-risk HMO sectors. STUDY DESIGN: A retrospective study that tracks the mortality rates and time until death of a random sample of 1,240,120 Medicare beneficiaries in the FFS sector and 1,526,502 enrollees in HMOs between April 1, 1993 and April 1, 1994. A total of 58,201 beneficiaries switched from an HMO to the FFS sector and were analyzed separately. PRINCIPAL FINDINGS: HMO enrollees have lower relative odds of mortality than a comparable group of FFS beneficiaries. Conversely, HMO disenrollees have higher relative odds of mortality than comparable FFS beneficiaries. Among decedents in the three groups, HMO enrollees lived longer than FFS beneficiaries, who in turn lived longer than HMO disenrollees. CONCLUSIONS: Medicare TEFRA-risk HMO enrollees appear to be, on average, healthier than beneficiaries enrolled in the FFS sector, who appear to be in turn healthier than HMO disenrollees. These health status differences persist, even after controlling for beneficiary demographics and county-level variables that might confound the relationship between mortality and the insurance sector. PMID- 11221819 TI - A longitudinal study of the effects of graduate medical education on hospital operating costs. AB - OBJECTIVE: To examine the effect of graduate medical education sponsorship on hospital operating costs over a seven-year period, to test for a longitudinal association between teaching intensity and cost, and to determine whether the indirect medical education (IME) payment adjustments made under Medicare's Prospective Payment System are appropriate. DATA SOURCES: Medicare cost and payment data from the Hospital Cost Report Information System and other related HCFA files, from FFY 1989 through 1995. The study population consists of all short-stay hospitals (approximately 5,000) participating in Medicare and receiving case payments by diagnosis-related groups. STUDY DESIGN: The original cost functions used to develop indirect medical education payment adjustments under PPS are re-estimated with panel data. Specification changes are included based on findings from critiques of the original hospital cost model. Additional variations on the model are explored to test for differences by hospital status, to control for the effect of additional disproportionate share and outlier payments, and to isolate the effects of improved case-mix measurement on model results. PRINCIPAL FINDINGS: Fixed effects regression produces no evidence of a significant within-hospital association between increased sponsorship of medical residents and increased cost per case. In models designed to capture a cross sectional association, operating costs are positively related to teaching activity, but the association shows a decline in strength over time. In all years, the strength of the association is significantly greater among hospitals eligible for disproportionate share adjustments and among major teaching hospitals. Controlling for secular trends of increased teaching intensity results in a pattern of declining cross-sectional teaching coefficients that supports a theory that observed teaching effects are the result of unmeasured case severity. CONCLUSIONS: A significant but declining cost differential is observed between teaching and nonteaching hospitals. The association appears to be related to hospital and patient characteristics that cannot be controlled using currently available case-mix and wage indices. Longitudinal models do not provide evidence to support a payment adjustment formula that allows individual hospitals to recompute their IME adjustment rates as their teaching ratios rise or fall from year to year. Cross-sectional findings suggest that re-estimations of the teaching effect may be appropriate when significant improvements occur in Medicare case-mix measurement. PMID- 11221820 TI - Differences in rehabilitation services and outcomes among stroke patients cared for in veterans hospitals. AB - OBJECTIVE: To examine the relationship of services for post-acute care (PAC) to stroke patient outcomes. DATA SOURCES/STUDY SETTING: Veterans Health Administration (VHA) hospitals from two facility-level surveys and extant data files. STUDY DESIGN: Cross-sectional study of veterans hospitalized with acute stroke during the period June 1995 through May 1996 in one of 182 geographically distinct locations within the VHA. Study variables included (1) a typological classification of hospitals according to the level of PAC; (2) a taxonomy of rehabilitation characteristics, including personnel, physical facilities, coordination of care, and hospital characteristics; and (3) patient outcomes (discharge destination, length of stay). DATA COLLECTION/EXTRACTION METHODS: Data were collected from two mailed surveys and extant data files. Rehabilitation variables were identified for the study in conjunction with a panel of expert rehabilitation researchers and clinicians, using an a priori model for measuring rehabilitation characteristics. Two sets of variables were derived to categorize these rehabilitation characteristics: (1) a rehabilitation typology, classifying the VA hospitals according to the continuum of PAC settings in the facility, and (2) a rehabilitation taxonomy that used an empirical approach to derive a list of key rehabilitation characteristics. PRINCIPAL FINDINGS: Twenty-seven percent of veterans with acute stroke were cared for in VA hospitals with neither a geriatric nor a rehabilitation unit, and 50 percent were cared for in hospitals without a rehabilitation unit. Hospitals with rehabilitation units had the greatest sophistication, and those with geriatric units had intermediate sophistication in rehabilitation organization and resources. Statistically significant differences were found in outcomes for stroke patients cared for in hospitals classified according to the continuum of post-acute care on site. Exploratory multivariable analyses revealed independent associations between stroke patient outcomes and (1) staffing ratios for nurses and physicians, (2) the diversity of physician and rehabilitation staff, (3) presence of a simulated home environment, and (4) the total number of care settings on site. CONCLUSIONS: The PAC continuum defines an important hierarchy of stroke rehabilitation services. PMID- 11221821 TI - The quick and the dead: "managing" inpatient care in British Columbia hospitals, 1969-1995/96. AB - OBJECTIVE: To examine changes in hospital use in British Columbia during a decade of capacity reductions. DATA SOURCES/STUDY SETTING: The data used are all separation records for British Columbia hospitals for the years 1969, 1978, 1985/86, 1993/94, and 1995/96. Separation records include acute care, rehabilitation, extended care, and surgical day care hospital encounters in British Columbia that were concluded during the years of interest. STUDY DESIGN: Analyses were based on per capita use of services for five-year age groups of the population to ages 90+; the emphasis was on looking at changes in the use of specific types of hospital services over the 26 years of study, with a particular focus on the most recent decade. DATA COLLECTION/EXTRACTION METHODS: Data were extracted from hospital separations files owned by the British Columbia Ministry of Health and housed at the Centre for Health Services and Policy Research. All separation records for the years of interest were included in the study. PRINCIPAL FINDINGS: Acute care use continued to fall over the last decade. The rate of decline increased during the last time period of study and affected seniors to the same degree as younger patients. At the same time, use of extended care decreased, compared to steady increases in earlier years. The result was that by 1995/96 nearly 40 percent of inpatient days were used by people who died in hospital, compared to 9 percent in 1969. These people, however, still represent a small proportion of separations. CONCLUSIONS: The "bed blocker" problem common to many hospital systems appears to have been largely alleviated in British Columbia over the decade 1985-95. The concurrent decrease in extended care use, however, makes it difficult to say where and how these people are now being cared for. Care for the dying has become a bigger issue for hospitals, but whether this is because of heroic interventions at the end of life is not clear. A "top-down," capacity-driven management approach to hospital use in British Columbia has produced effects that may seem familiar to those involved in more "bottom-up" managed care approaches in the United States. PMID- 11221822 TI - The use of monetary incentives in a community survey: impact on response rates, data quality, and cost. AB - OBJECTIVES: To assess the effect of incentive size on response rates, data quality, and cost in a digestive health status mail survey of a community sample of health plan enrollees. DATA SOURCES/SETTING: The study population was selected from a database of enrollees in various health plans obligated to receive care at Park Nicollet Clinic-HealthSystem Minnesota, a large, multispecialty group in Minneapolis, Minnesota, and the nearby suburbs. STUDY DESIGN: A total of 1,800 HealthSystem Minnesota enrollees were randomly assigned to receive a survey with an incentive of $5 or $2. The response rates for each incentive level were determined. Data quality, as indicated by item nonresponse and scale scores, was measured. Total cost and cost per completed survey were calculated. PRINCIPAL FINDINGS: The response rate among enrollees receiving $5 (74.3 percent) was significantly higher than among those receiving $2 (67.4 percent); differences were more pronounced in the first wave of data collection. Data quality did not differ between the two incentive groups. The total cost per completed survey was higher in the $5 condition than in the $2 condition. CONCLUSIONS: A $5 incentive resulted in a higher response rate among a community patient sample with one mailing than did a $2 incentive. However, the response rates in the $2 condition approached the level of the $5 incentive, and costs were significantly lower when the full follow-up protocol was completed. Response rates were marginally increased by follow-up phone calls. The incentive level did not influence data quality. The results suggest if a survey budget is limited and a timeline is not critical, a $2 incentive provides an affordable means of increasing participation. PMID- 11221823 TI - Reported response rates to mailed physician questionnaires. AB - OBJECTIVE: To examine response rate information from mailed physician questionnaires reported in published articles. DATA SOURCES/STUDY SETTING: Citations for articles published between 1985 and 1995 were obtained using a key word search of the Medline, PsychLit, and Sociofile databases. STUDY DESIGN: A 5 percent random sample of relevant citations was selected from each year. DATA COLLECTION/EXTRACTION METHODS: Citations found to be other than physician surveys were discarded and replaced with the next randomly assigned article. Selected articles were abstracted using a standardized variable list. PRINCIPAL FINDINGS: The average response rate for mailed physician questionnaires was 61 percent. The average response rate for large sample surveys (> 1,000 observations) was 52 percent. In addition, only 44 percent of the abstracted articles reported a discussion of response bias, and only 54 percent reported any type of follow-up. CONCLUSIONS: (1) Response rates have remained somewhat constant over time, and (2) researchers need to document the efforts used to increase response rates to mailed physician questionnaires. PMID- 11221824 TI - Methodological biases in estimating the burden of out-of-pocket expenses. PMID- 11221825 TI - A molecular variant of the APC gene at codon 1822: its association with diet, lifestyle, and risk of colon cancer. AB - The adenomatous polyposis coli (APC) gene is important in the etiology of colon cancer. Although germ-line mutations of this gene rarely occur in the population, less penetrant variants of the gene have been reported. One variant, producing an aspartate to valine change at codon 1822 (D1822V) [corrected] has been previously reported as having an allele frequency of 10%. The purpose of this study was to determine whether this D1822V [corrected] variant of the APC gene is associated with colon cancer and whether its association is influenced by other genetic or environmental factors. We used data collected as part of a multicenter study of 1,585 incident cases of colon cancer and 1,945 age- and sex-matched population based controls to evaluate genetic, dietary, and environmental associations with the D1822V [corrected] variant of the APC gene. The frequency of the valine/valine allele at codon 1,822 was 22.8% in this population. In the control population, 61.5% were homozygote wild type, 33.3% were heterozygotes, and 5.2% were homozygote variant. Cases were slightly less likely to have the homozygous variant APC genotype than were controls [odds ratio (OR), 0.8; 95% confidence interval (CI), 0.6-1.1]; for those diagnosed after age 65, the homozygous APC variant was associated with reduced risk of colon cancer (OR, 0.6; 95% CI, 0.4 1.0). Assessment of the homozygous APC variant with dietary, genetic, and environmental factors showed that individuals with this genotype were at lower risk if they consumed a low-fat diet (OR, 0.2; 95% CI, 0.1-0.5) relative to those who were homozygous wild type and ate a high-fat diet. This finding was specific to a low-fat diet and was unrelated to other dietary variables. These results suggest that the codon 1,822 variant of the APC gene may have functional significance. Individuals who have the valine/valine variant of this gene may be at reduced risk of colon cancer if they eat a low-fat diet.